Welcome to TiddlyWiki created by Jeremy Ruston; Copyright © 2004-2007 Jeremy Ruston, Copyright © 2007-2011 UnaMesa Association
<html><a name="HC001002"></a> <br><a name="PB001001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Pulse oximetry</b> is a noninvasive test for measuring Sao<sub>2</sub>. It utilizes a probe that is usually clipped over a patient's finger. Oximetry emits light at specified wavelengths that identify oxyhemoglobin and deoxyhemoglobin, respectively. The wavelengths emitted by a pulse oximeter <i>cannot</i> identify dyshemoglobins such as methemoglobin (metHb) and carboxyhemoglobin (i.e., carbon monoxide bound to Hb, COHb), which normally decrease the Sao<sub>2</sub> (see later). In the presence of these dyshemoglobins, the oximeter calculates a falsely high Sao<sub>2</sub>. Unlike the standard oximeter, a co-oximeter emits multiple wavelengths and calculates an accurate Sao<sub>2</sub> because it identifies metHb and COHb.</div><a name="P001001"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hypoxia refers to inadequate oxygenation of tissue.
<blockquote style="color: blue; ">Hypoxia: inadequate oxygenation of tissue</blockquote></li><li>Inadequate oxygen (O<sub>2</sub>) decreases synthesis of adenosine triphosphate (ATP).</li><ol type="a"> <li>ATP synthesis occurs in the inner mitochondrial membrane by the process of oxidative phosphorylation (see later).</li><li>O<sub>2</sub> is an electron acceptor located at the end of the electron transport chain (ETC) in the oxidative pathway.</li><li>A lack of O<sub>2</sub> or a defect in oxidative phosphorylation culminates in a decrease in ATP synthesis.</li> </ol><li>Several types of hypoxia produce O<sub>2</sub>-related changes reported with arterial blood gas measurements (<span>[[Table 1-1|Table 1-1. TERMINOLOGY ASSOCIATED WITH OXYGEN TRANSPORT AND HYPOXIA]]</span>).
<blockquote style="color: blue; ">O<sub>2</sub> content = (Hb g/dL × 1.34) × Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> + Pao<sub>2</sub> × 0.003</blockquote></li><ul> <li>O<sub>2</sub> diffuses down a gradient from the alveoli, to plasma (↑Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>), and to red blood cells (RBCs), where it attaches to heme groups (↑Sao<sub>2</sub>)</li> </ul><li>Clinical findings of hypoxia include cyanosis (see <span>[[Fig. 10-11|Figure 10-11]]</span>), confusion, cognitive impairment, and lethargy.
<blockquote style="color: blue; ">Pulse oximeter: falsely ↑ Sao<sub>2</sub> with metHb and COHb</blockquote></li> </ol>
</div></html>
<html><a name="HC001003"></a> <br><a name="PB001002"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Methemoglobin</b> is converted to the ferrous state (Fe<sup>2+</sup>) by the reduced nicotinamide adenine dinucleotide (NADH) reductase system located off the glycolytic pathway in RBCs. Electrons from NADH are transferred to cytochrome <i>b</i><sub>5</sub> and then to metHb by cytochrome <i>b</i><sub>5</sub> reductase to produce ferrous Hb. Newborns are particularly at risk for developing methemoglobinemia after oxidant stresses (see later) owing to decreased levels of cytochrome <i>b</i><sub>5</sub> reductase until at least 4 months of age.</div><a name="PB001003"></a><div class="BB" style="color: rgb(47, 79, 79); ">Patients with <b>methemoglobinemia</b> have chocolate-colored blood (increased concentration of deoxyhemoglobin) and cyanosis. Clinically evident cyanosis occurs at metHb levels greater than 1.5 g/dL. Skin color does <i>not</i> return to normal after administration of O<sub>2</sub>. Treatment is intravenous methylene blue, which acts as an artificial electron carrier in the reduced nicotinamide adenine dinucleotide phosphate (NADPH) metHb reductase system located in the pentose phosphate shunt.</div><a name="P001002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Ischemia</li><ol type="a"> <li>Decreased arterial blood flow or venous outflow of blood</li><li>Examples-coronary artery atherosclerosis, decreased cardiac output, thrombosis of splenic vein
<blockquote style="color: blue; ">Ischemia: ↓ arterial blood inflow or venous outflow</blockquote></li><li>Consequences of ischemia</li><ul> <li>(1) Atrophy (reduction in cell/tissue mass)</li><li>(2) Infarction of tissue (localized area of tissue necrosis)</li><li>(3) Organ dysfunction (e.g., heart failure)</li> </ul> </ol><li>Hypoxemia
<blockquote style="color: blue; ">Hypoxemia: ↓Pao<sub>2</sub></blockquote></li><ul> <li>Normal ventilation and perfusion are depicted in <span>[[Figure 1-1A|Figure 1-1]]</span>.</li><ol type="a"> <li>Decrease in Pao<sub>2</sub> (<40 mm Hg)</li><li>Causes</li><ul> <li>(1) Decreased inspired Po<sub>2</sub> (Pio<sub>2</sub>)</li><ul> <li>Examples-high altitude, breathing reduced %O<sub>2</sub> mist</li> </ul><li>(2) Respiratory acidosis (hypoventilation)</li><ul> <li>(a) Carbon dioxide (CO<sub>2</sub>) retention in the lungs <i>always</i> produces a corresponding decrease in Pao<sub>2</sub>.
<blockquote style="color: blue; ">↑Alveolar P<span style="font-variant:small-caps;">co</span><sub>2</sub> = ↓ alveolar Po<sub>2</sub> = ↓ Pao<sub>2</sub> = ↓ Sao<sub>2</sub></blockquote></li><li>(b) Examples-depression of the medullary respiratory center (e.g., barbiturates), paralysis of the diaphragm, chronic bronchitis</li> </ul><li>(3) Ventilation defect (<span>[[Fig. 1-1B|Figure 1-1]]</span>)</li><ul> <li>(a) Impaired O<sub>2</sub> delivery to alveoli</li><ul> <li>Example-respiratory distress syndrome (RDS) with collapse of the distal airways due to lack of surfactant</li> </ul><li>(b) No O<sub>2</sub> exchange in lungs that are perfused but <i>not</i> ventilated
<blockquote style="color: blue; ">Ventilation defect: perfused but <i>not</i> ventilated; intrapulmonary shunt</blockquote></li><li>(c) Diffuse disease (RDS) produces intrapulmonary shunting of blood</li><ul> <li>Pulmonary capillary blood has the same Po<sub>2</sub> and P<span style="font-variant:small-caps;">co</span><sub>2</sub> as venous blood returning from tissue (i.e., a large fraction of pulmonary blood flow has <i>not</i> been arterialized).</li> </ul><li>(d) Inspired %O<sub>2</sub> from 0.24% to 0.28% or greater does <i>not</i> significantly increase the Pao<sub>2</sub>.</li><ul> <li>This only applies to a diffuse ventilation defect involving both lungs; smaller defects are compensated for in normally ventilated lung.</li> </ul> </ul><li>(4) Perfusion defect (<span>[[Fig. 1-1C|Figure 1-1]]</span>)</li><ul> <li>(a) Absence of blood flow to alveoli (e.g., pulmonary embolus)</li><li>(b) No O<sub>2</sub> exchange in lungs that are ventilated but <i>not</i> perfused
<blockquote style="color: blue; ">Perfusion defect: ventilated but <i>not</i> perfused; ↑ dead space</blockquote></li><li>(c) Produces an increase in dead space</li><ul> <li>Exchange of O<sub>2</sub> and CO<sub>2</sub> does <i>not</i> occur.</li> </ul><li>(d) Inspired %O<sub>2</sub> from 0.24% to 0.28% or greater increases the Pao<sub>2</sub>.</li><ul> <li>Other parts of ventilated and perfused lung have normal gas exchange.</li> </ul> </ul><li>(5) Diffusion defect
<blockquote style="color: blue; ">Diffusion defect: interstitial fibrosis, pulmonary edema</blockquote></li><ul> <li>(a) Decreased O<sub>2</sub> diffusion through the alveolar-capillary interface</li><li>(b) Examples-interstitial fibrosis, pulmonary edema</li> </ul><li>(6) Ventilation, perfusion, and diffusion defects increase the difference in O<sub>2</sub> concentration between alveolar Po<sub>2</sub> (P<span style="font-variant:small-caps;">ao</span><sub>2</sub>) and arterial Po<sub>2</sub> (Pao<sub>2</sub>).</li><ul> <li>This difference is called the alveolar-arterial (<span style="font-variant:small-caps;">a</span>-a) gradient (refer to <span macro="tag [[16 Upper and Lower Respiratory Disorders]] [[Chapter 16]]"></span>).</li> </ul> </ul> </ol> </ul><li>Hemoglobin (Hb)-related abnormalities</li><ol type="a"> <li>Anemia</li><ul> <li>(1) Decreased Hb concentration (<7 g/dL)</li><li>(2) Causes</li><ul> <li>(a) Decreased production of Hb (e.g., iron deficiency)</li><li>(b) Increased destruction of RBCs (e.g., hereditary spherocytosis)</li><li>(c) Decreased production of RBCs (e.g., aplastic anemia)</li><li>(d) Increased sequestration of RBCs (e.g., splenomegaly)
<blockquote style="color: blue; ">Anemia: normal Pao<sub>2</sub> and Sao<sub>2</sub></blockquote></li> </ul><li>(3) Normal Pao<sub>2</sub> and Sao<sub>2</sub></li> </ul><li>Methemoglobinemia</li><ul> <li>(1) Methemoglobin (metHb) is Hb with oxidized heme groups (Fe<sup>3+</sup>).</li><li>(2) Causes</li><ul> <li>(a) Oxidant stresses</li><ul> <li>Examples-nitrite- and sulfur-containing drugs, sepsis, local anesthetics (e.g., benzocaine)</li> </ul><li>(b) Congenital deficiency of cytochrome <i>b</i><sub>5</sub> reductase</li> </ul><li>(3) Pathogenesis of hypoxia</li><ul> <li>(a) Fe<sup>3+</sup> cannot bind O<sub>2</sub>
<blockquote style="color: blue; ">MetHb: heme Fe<sup>3+</sup>; ↓ Sao<sub>2</sub></blockquote></li><ul> <li>Normal Pao<sub>2</sub>, decreased Sao<sub>2</sub></li> </ul><li>(b) Ferric heme groups impair unloading of O<sub>2</sub> by oxygenated ferrous heme.</li><ul> <li>This causes a left-shifted O<sub>2</sub>-binding curve (see later).
<blockquote style="color: blue; ">MetHb: Rx with IV methylene blue</blockquote></li> </ul> </ul> </ul><li>Carbon monoxide (CO) poisoning (also refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>)</li><ul> <li>(1) Leading cause of death due to poisoning</li><li>(2) Produced by incomplete combustion of carbon-containing compounds</li><li>(3) Causes include automobile exhaust, smoke inhalation, wood stoves, methylene chloride (paint thinner).</li><li>(4) Pathogenesis of hypoxia</li><ul> <li>(a) CO competes with O<sub>2</sub> for binding sites on Hb.</li><ul> <li>Decreases Sao<sub>2</sub> <i>without</i> affecting Pao<sub>2</sub>
<blockquote style="color: blue; ">CO poisoning: normal Pao<sub>2</sub>, ↓Sao<sub>2</sub></blockquote></li> </ul><li>(b) CO inhibits cytochrome oxidase in the electron transport chain (ETC).</li><li>(c) CO causes a left-shifted O<sub>2</sub>-binding curve (OBC).</li> </ul><li>(5) Clinical findings</li><ul> <li>(a) Cherry-red discoloration of skin and blood</li><li>(b) Headache (first symptom at levels of 10-20%)</li><li>(c) Dyspnea, dizziness (levels of 20-30%)</li><li>(d) Seizures, coma (levels of 50-60%)</li><li>(e) Lactic acidosis due to hypoxia
<blockquote style="color: blue; ">Rx CO poisoning: O<sub>2</sub> via nonbreather mask</blockquote></li> </ul><li>(6) Treatment is O<sub>2</sub> via nonbreather mask or endotracheal tube (100% O<sub>2</sub>)</li> </ul><li>Factors causing a left-shifted OBC</li><ul> <li>(1) Decreased 2,3-bisphosphoglycerate (BPG)</li><ul> <li>Intermediate of glycolysis via conversion of 1,3-BPG to 2,3-BPG</li> </ul><li>(2) CO, alkalosis, metHb, fetal Hb, hypothermia</li><li>(3) These factors increase affinity of Hb for O<sub>2</sub> with less release of O<sub>2</sub> to tissue.</li><ul> <li>Example-at the capillary Po<sub>2</sub> concentration in tissue a right-shifted OBC (↑2,3-BPG, acidosis, fever) has released most of its O<sub>2</sub> to tissue, but a left-shifted OBC still has most of its O<sub>2</sub> attached to heme groups (<span>[[Fig. 1-2|Figure 1-2]]</span>).
<blockquote style="color: blue; ">High altitude: ↑ 2,3-BPG synthesis; respiratory alkalosis</blockquote></li> </ul> </ul> </ol> </ol>
</div><a name="PB001004"></a><div class="BB" style="color: rgb(47, 79, 79); ">At <b>high altitudes,</b> the atmospheric pressure is decreased; however, the percentage of O<sub>2</sub> in the atmosphere remains the same (i.e., 21%). Hypoxemia stimulates peripheral chemoreceptors (e.g., carotid body) causing respiratory alkalosis, which shifts the OBC to the left. However, alkalosis activates phosphofructokinase, the rate-limiting enzyme in glycolysis, causing increased production of 1,3-BPG, which is converted to 2,3-BPG. This eventually shifts the OBC to the right, leading to increased release of O<sub>2</sub> to tissue.</div></html>
<html><a name="HC001004"></a> <br><a name="PB001005"></a><div class="BB" style="color: rgb(47, 79, 79); ">The <b>oxidative part of the pathway</b> in the inner mitochondrial membrane transfers donated electrons from NADH and reduced flavin adenine dinucleotide (FADH<sub>2</sub>) derived from the energy cycles down the ETC to O<sub>2</sub>. Oxygen is a strong electron acceptor located at the end of the chain on complex IV. The transfer of electrons is coupled with the transport of protons (H<sup>+</sup>) supplied by NADH and FADH<sub>2</sub> across the inner mitochondrial membrane into the intermembranous space, which establishes both a proton and a pH gradient. The <b>phosphorylation part of the pathway</b> is the synthesis of ATP. A certain amount of heat is required to synthesize ATP. ATP synthesis occurs when the protons on the cytosolic side of the inner membrane enter small channels (proton pores) within the ATP synthase molecule (complex V) and reenter the mitochondrial matrix, where ATP is synthesized. The inner mitochondrial membrane is normally impermeable to protons except through the channel in the ATP synthase molecule. This relationship is critical to the maintenance of the proton gradient. If enzymatic reactions in electron transport are inhibited (e.g., cytochrome oxidase), the formation of protons and the proton gradient are disrupted as well, leading to a decrease in ATP synthesis.</div><a name="P001003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Enzyme inhibition of oxidative phosphorylation (<span>[[Fig. 1-3|Figure 1-3]]</span>)</li><ol type="a"> <li>Enzyme inhibition of oxidative phosphorylation</li><ul> <li>(1) Synthesis of ATP is decreased.</li><li>(2) CO and cyanide (CN) inhibit cytochrome oxidase in the ETC.
<blockquote style="color: blue; ">CO and CN: inhibit cytochrome oxidase</blockquote></li><li>(3) CN poisoning (also refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>)</li><ul> <li>(a) It may result from drugs (e.g., nitroprusside) and combustion of polyurethane products in house fires.</li><li>(b) It produces an initial central nervous system and cardiovascular stimulation followed by CNS depression and death.
<blockquote style="color: blue; ">CO and CN poisoning: house fires</blockquote></li><li>(c) It produces lactic acidosis due to hypoxia.</li><li>(d) It produces increased venous Po<sub>2</sub> and saturation.</li><ul> <li>Tissue <i>cannot</i> extract O<sub>2</sub>.</li> </ul><li>(e) Treatment involves two stages.
<blockquote style="color: blue; ">Rx CN poisoning: amyl nitrite, thiosulfate</blockquote></li><ul> <li>Amyl nitrite (produces metHb which combines with CN to form cyanmetHb) followed by thiosulfate (CN converted to thiocyanate)</li> </ul> </ul> </ul><li>Uncoupling of oxidative phosphorylation</li><ul> <li>(1) Uncoupling proteins carry protons in the intermembranous space through the inner mitochondrial membrane into the mitochondrial matrix without damaging the membrane.
<blockquote style="color: blue; ">Uncouplers: thermogenin, dinitrophenol</blockquote></li><ul> <li>(a) Bypass of ATP synthase causes decreased synthesis of ATP.</li><li>(b) Examples-thermogenin (natural uncoupler in brown fat in newborns), dinitrophenol used in synthesizing nitroglycerin</li> </ul><li>(2) Heat normally used to synthesize ATP raises the core body temperature.</li><ul> <li>(a) There is a danger of developing hyperthermia with dinitrophenol.</li><li>(b) Thermogenin is useful in stabilizing body temperature in newborns.
<blockquote style="color: blue; ">Mitochondrial toxins: alcohol, salicylates</blockquote></li> </ul> </ul> </ol> </ol>
</div><a name="PB001006"></a><div class="BB" style="color: rgb(47, 79, 79); ">Agents such as <b>alcohol</b> and <b>salicylates</b> act as mitochondrial toxins. They damage the inner mitochondrial membrane, causing protons to move into the mitochondrial matrix. As with dinitrophenol, hyperthermia is a common complication in alcohol and salicylate poisoning.</div></html>
<html><a name="HC001005"></a> <br><a name="PB001007"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Factors decreasing coronary artery blood flow</b> (e.g., coronary artery atherosclerosis) produce subendocardial ischemia, which is manifested by chest pain (i.e., angina) and ST-segment depression in an electrocardiogram (ECG). Increased thickness of the left ventricle (i.e., hypertrophy) in the presence of increased myocardial demand for O<sub>2</sub> (e.g., exercise) can also produce subendocardial ischemia.</div><a name="P001004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Watershed areas between terminal branches of major arterial blood supplies
<blockquote style="color: blue; ">Watershed areas: cerebral vessels, mesenteric arteries</blockquote></li><ol type="a"> <li>The blood supply from the two vessels does <i>not</i> overlap.</li><li>Examples</li><ul> <li>(1) Area between the distribution of the anterior and middle cerebral arteries (<span>[[Fig. 1-4|Figure 1-4]]</span>)</li><li>(2) Area between the distribution of the superior and inferior mesenteric arteries (i.e., splenic flexure)</li> </ul> </ol><li>Subendocardial tissue</li><ol type="a"> <li>Coronary vessels penetrate the epicardial surface.</li><li>Subendocardial tissue receives the <i>least</i> amount of O<sub>2</sub>.
<blockquote style="color: blue; ">ST-segment depression ECG: subendocardial ischemia</blockquote></li> </ol><li>Renal cortex and medulla</li><ol type="a"> <li>In the cortex, the straight portion of the proximal tubule is most susceptible to hypoxia.</li><ul> <li>Primary site for reclaiming bicarbonate and reabsorbing sodium</li> </ul><li>In the medulla, the Na<sup>+</sup>-K<sup>+</sup>-2 Cl<sup>-</sup> cotransport channel in the thick ascending limb is most susceptible to hypoxia.</li><ul> <li>Primary site for regenerating free water, which is necessary for normal dilution and concentration of urine.</li> </ul> </ol><li>Neurons in the central nervous system
<blockquote style="color: blue; ">Neurons: most adversely affected cell in tissue hypoxia</blockquote></li><ol type="a"> <li>Examples-Purkinje cells in cerebellum, neurons in layers 3, 5, and 6 of the cerebral cortex</li><li>Irreversible damage occurs ∼5 minutes after global hypoxia.</li> </ol><li>Hepatocytes located around the central vein
<blockquote style="color: blue; ">Zone III hepatocytes: most susceptible to hypoxia</blockquote></li> </ol>
</div><a name="PB001008"></a><div class="BB" style="color: rgb(47, 79, 79); ">In the <b>portal triads,</b> hepatic artery tributaries carrying oxygenated blood and portal vein tributaries carrying unoxygenated blood empty their blood into the liver sinusoids (mixed oxygenated and unoxygenated blood), which drain blood into the central veins (terminal hepatic venules). The central veins become the hepatic vein, which empties into the inferior vena cava. Hepatocytes closest to the portal triads (zone I) receive the most oxygen and nutrients, and those farthest from the portal triads (zone III around the central vein) receive the least amount of oxygen and nutrients. Production of free radicals from drugs (e.g., acetaminophen, see later), tissue hypoxia (e.g., shock, CO poisoning), and alcohol-related fatty change of the liver initially damage zone III hepatocytes.</div></html>
<html><a name="HC001006"></a> <br><a name="P001005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Decreased synthesis of ATP</li><li>Anaerobic glycolysis is used for ATP synthesis and is accompanied by several changes-</li><ol type="a"> <li>Activation of phosphofructokinase</li><ul> <li>Caused by low citrate levels and increased adenosine monophosphate</li> </ul><li>Net gain of 2 ATP
<blockquote style="color: blue; ">Anaerobic glycolysis: primary source ATP in hypoxia; lactic acidosis</blockquote></li><li>Decrease in intracellular pH caused by an excess of lactate</li><ul> <li>(1) Also accumulates in blood producing lactic acidosis</li><li>(2) Denatures structural and enzymic proteins</li> </ul><li>Impaired Na<sup>+</sup>/K<sup>+</sup>-ATPase pump</li><ul> <li>(1) Diffusion of Na<sup>+</sup> and H<sub>2</sub>O into cells causes cellular swelling.</li><li>(2) Potentially reversible with restoration of O<sub>2</sub></li> </ul> </ol><li>Decreased protein synthesis</li><ul> <li>Due to detachment of ribosomes (potentially reversible)</li> </ul><li>Irreversible cell changes
<blockquote style="color: blue; ">↑Ca<sup>2+</sup> in cytosol: "point of no return"; activates enzymes</blockquote></li><ol type="a"> <li>Impaired calcium (Ca<sup>2+</sup>)-ATPase pump</li><ul> <li>Normal function of the pump is to keep Ca<sup>2+</sup> out of the cytosol.</li> </ul><li>Increased cytosolic Ca<sup>2+</sup> has two lethal effects.</li><ul> <li>(1) Enzyme activation</li><ul> <li>(a) Phospholipase increases cell and organelle membrane permeability.</li><li>(b) Proteases damage the cytoskeleton.</li><li>(c) Endonucleases cause fading of nuclear chromatin (karyolysis).</li> </ul><li>(2) Reentry of Ca<sup>2+</sup> into mitochondria</li><ul> <li>(a) Increases mitochondrial membrane permeability
<blockquote style="color: blue; ">Cytochrome <i>c</i> in cytosol: activates apoptosis (cell death)</blockquote></li><li>(b) Release of cytochrome <i>c</i> into the cytosol activates apoptosis (see later)</li> </ul> </ul> </ol> </ol>
</div></html>
![[1.I.A.Hypoxia]]
<<tiddler [[1.I.A.Hypoxia]]>>
![[1.I.B.Causes of tissue hypoxia]]
<<tiddler [[1.I.B.Causes of tissue hypoxia]]>>
![[1.I.C.Mitochondrial causes of ATP depletion]]
<<tiddler [[1.I.C.Mitochondrial causes of ATP depletion]]>>
![[1.I.D.Tissues susceptible to hypoxia]]
<<tiddler [[1.I.D.Tissues susceptible to hypoxia]]>>
![[1.I.E.Consequences of hypoxic cell injury]]
<<tiddler [[1.I.E.Consequences of hypoxic cell injury]]>>
<html><a name="HC001008"></a> <br><a name="P001010"></a><div class="PA" style="color: black; "><ul> <li>Unstable chemical compounds with a single unpaired electron in their outer orbital</li> </ul>
</div></html>
<html><a name="HC001009"></a> <br><a name="P001011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Produced by-</li><ol type="a"> <li>Ionizing radiation</li><ul> <li>Produces hydroxyl FRs
<blockquote style="color: blue; ">Hydroxyl FRs: most destructive FRs</blockquote></li> </ul><li>Damaged mitochondria</li><ul> <li>Produce superoxide FRs</li> </ul><li>High concentration of O<sub>2</sub></li><ul> <li>(1) Produces superoxide and hydroxyl FRs</li><li>(2) Produces hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)</li><ul> <li>A reactive oxygen species that produces hydroxyl and peroxide FRs.</li> </ul> </ul><li>Oxidase reactions
<blockquote style="color: blue; ">Oxidase reactions: produce superoxide FRs</blockquote></li><ul> <li>(1) NADPH oxidase in the neutrophil and monocyte cell membrane</li><ul> <li>(a) Myeloperoxidase in a phagolysosome combines hydrogen peroxide with chloride to form bleach (hypochlorous acid).</li><li>(b) Hypochlorous acid is a reactive oxygen species that can generate FRs.</li> </ul><li>(2) Xanthine oxidase acting upon xanthine (degradation product of ATP)</li><ul> <li>Produces superoxide FRs</li> </ul> </ul><li>Drugs (e.g., acetaminophen)
<blockquote style="color: blue; ">Acetaminophen: drug FRs formed in liver</blockquote></li><ul> <li>Converted to acetaminophen FRs in the liver</li> </ul><li>Carbon tetrachloride</li><ul> <li>Converted to CCl<sub>3</sub> FRs in the liver</li> </ul><li>Cigarette smoke</li><ul> <li>(1) Produces quinone/hydroquinone FRs produced from tar</li><li>(2) Produces nitric oxide (NO), an FR gas</li><ul> <li>NO reacts with other reactive species (e.g., isoprene) to produce additional FRs.</li> </ul> </ul><li>Pollution</li><ul> <li>Nitrogen dioxide in car exhaust and ozone produce nitrate FRs.</li> </ul><li>Metals (e.g., iron, copper)
<blockquote style="color: blue; ">Iron, copper: generate hydroxyl FRs</blockquote></li><ul> <li>Produce hydroxyl FRs (called the Fenton reaction)</li> </ul><li>Nitric oxide</li><ul> <li>FR gas that is produced by macrophages and endothelial cells.</li> </ul><li>Intima of elastic and muscular arteries</li><ul> <li>(1) Small dense subtypes of low density lipoprotein (LDL) enter the intima and are oxidized by FRs produced by macrophages, smooth muscle cells, and endothelial cells.</li><li>(2) Oxidized LDL contributes to formation of fatty streaks, which are progenitors of fibrous caps, the pathognomonic lesion of atherosclerosis.</li> </ul> </ol><li>FRs attack a molecule and "steal" its electron.</li><ol type="a"> <li>The attacked molecule becomes an FR that begins a chain reaction leading to cell death.</li><li>FRs primarily target nucleic acids and membrane molecules.
<blockquote style="color: blue; ">Free radicals: damage membranes and DNA</blockquote></li><ul> <li>(1) FRs produce DNA fragmentation and dissolution.</li><li>(2) FRs initiate lipid peroxidation of polyunsaturated lipids in cell and mitochondrial membranes.</li><ul> <li>(a) Lipid FRs combine with molecular O<sub>2</sub>.</li><li>(b) Increases membrane permeability leading to increased cytosol Ca<sup>2+</sup> concentration (see section ID).</li> </ul> </ul><li>FR damage accumulates with age; important in the aging process</li> </ol> </ol>
</div></html>
<html><a name="HC001010"></a> <br><a name="P001012"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Neutralization of FRs: SOD, GSH, vitamins C and E</blockquote>
<ol type="1"> <li>Superoxide dismutase (SOD)</li><ul> <li>Converts superoxide free radicals to peroxide and O<sub>2</sub></li> </ul><li>Glutathione peroxidase (enhances glutathione, GSH)</li><ol type="a"> <li>Located in the pentose phosphate pathway</li><li>Neutralizes H<sub>2</sub>O<sub>2</sub>, hydroxyl, and acetaminophen FRs</li> </ol><li>Catalase (present in peroxisomes)</li><ul> <li>Degrades peroxide into O<sub>2</sub> and water</li> </ul><li>Vitamins as antioxidants</li><ol type="a"> <li>Antioxidants neutralize FRs by donating one of their own electrons.</li><ul> <li>(1) Stops the "electron stealing" of FRs</li><li>(2) Antioxidants remain stable and do <i>not</i> become an FR.</li> </ul><li>Vitamin E (fat-soluble vitamin)</li><ul> <li>(1) Prevents lipid peroxidation in cell membranes</li><li>(2) Neutralizes oxidized LDL</li> </ul><li>Vitamin C (water-soluble vitamin)
<blockquote style="color: blue; ">Vitamin C: best neutralizer of hydroxyl FRs</blockquote></li><ul> <li>(1) Neutralizes FRs produced by pollutants and cigarette smoke</li><ul> <li>Smokers have decreased levels of vitamin C because they are used up in neutralizing FRs derived from cigarette smoke.</li> </ul><li>(2) Best neutralizer of hydroxyl FRs</li> </ul> </ol><li>Selenium</li><ul> <li>Neutralizes FRs in the cytosol</li> </ul> </ol>
</div></html>
<html><a name="HC001011"></a> <br><a name="P001013"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acetaminophen FRs
<blockquote style="color: blue; ">Acetaminophen: FR injury liver and kidneys</blockquote></li><ol type="a"> <li>May cause diffuse chemical hepatitis</li><ul> <li>(1) Liver cell necrosis initially occurs around the central veins (zone III).</li><ul> <li>(a) Can occur at nontoxic levels in alcoholics</li><li>(b) Produces transient decrease in functional factor VII</li><ul> <li>Prolongs the prothrombin time (PT)</li> </ul> </ul><li>(2) Treatment with <i>N</i>-acetylcysteine
<blockquote style="color: blue; "><i>N</i>-acetylcysteine: generates GSH</blockquote></li><ul> <li>Increases synthesis of glutathione for neutralization of drug FRs.</li> </ul> </ul><li>May cause renal papillary necrosis (see <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)</li><ul> <li>Necrosis occurs in association with the use of nonsteroidal anti-inflammatory agents.</li> </ul> </ol><li>Carbon tetrachloride free radicals</li><ul> <li>Produce liver cell necrosis with fatty change</li> </ul><li>Ischemia/reperfusion injury in acute myocardial infarction (see <span macro="tag [[10 Heart Disorders]] [[Chapter 10]]"></span>)</li><ol type="a"> <li>Occurs with restoration of blood flow to ischemic myocardium
<blockquote style="color: blue; ">Reperfusion injury: superoxide FRs and ↑ cytosolic Ca<sup>2+</sup></blockquote></li><li>Superoxide FRs and cytosolic Ca<sup>2+</sup> irreversibly damage previously injured cells.</li> </ol><li>Retinopathy of prematurity</li><ul> <li>Blindness may occur in the treatment of RDS with an O<sub>2</sub> concentration > 50%.</li> </ul><li>Iron overload disorders</li><ol type="a"> <li>Examples include hemochromatosis and hemosiderosis (see <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>).</li><li>Intracellular iron produces hydroxyl FRs, which damage parenchymal cells.</li><ul> <li>Examples of injury-cirrhosis, exocrine/endocrine pancreatic dysfunction</li> </ul> </ol><li>Copper overload (Wilson's disease)</li><ol type="a"> <li>Inability to excrete copper into bile</li><li>Copper excess in hepatocytes increases production of hydroxyl FRs
<blockquote style="color: blue; ">Excess iron and copper: hydroxyl FR damage of tissue</blockquote></li><ul> <li>Damage to hepatocytes produces cirrhosis</li> </ul> </ol> </ol>
</div></html>
![[1.II.A.Definition of free radicals]]
<<tiddler [[1.II.A.Definition of free radicals]]>>
![[1.II.B.Formation, function, types of free radicals (FRs)]]
<<tiddler [[1.II.B.Formation, function, types of free radicals (FRs)]]>>
![[1.II.C.Neutralization of FRs]]
<<tiddler [[1.II.C.Neutralization of FRs]]>>
![[1.II.D.Examples of FR injury]]
<<tiddler [[1.II.D.Examples of FR injury]]>>
<html><a name="HC001013"></a> <br><a name="P001014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Release of cytochrome <i>c</i> from injured mitochondria</li><ul> <li>Initiates apoptosis by activating caspases in the cytosol (see later).</li> </ul><li>Injurious agents include alcohol, salicylates, and increased cytosolic Ca<sup>2+</sup>.</li><ul> <li>Salicylates and alcohol produce megamitochondria (<span>[[Fig. 1-5|Figure 1-5]]</span>) with destruction of the cristae.</li> </ul> </ol>
</div></html>
<html><a name="HC001014"></a> <br><a name="P001015"></a><div class="PA" style="color: black; "><ol type="1"> <li>Induction of enzymes of the liver cytochrome P-450 system</li><ol type="a"> <li>May be caused by:</li><ul> <li>Alcohol, barbiturates, phenytoin</li> </ul><li>Causes SER hyperplasia (see <span>[[Fig. 1-5|Figure 1-5]]</span>)</li><ul> <li>Increased drug detoxification with lower-than-expected therapeutic drug levels
<blockquote style="color: blue; ">SER hyperplasia: ↑ drug metabolism</blockquote></li> </ul> </ol><li>Inhibition of enzymes of the cytochrome P-450 system</li><ol type="a"> <li>May be caused by:</li><ul> <li>(1) Proton receptor blockers (e.g., omeprazole)</li><li>(2) Macrolides (e.g., erythromycin)</li><li>(3) Histamine blockers (e.g., cimetidine)</li> </ul><li>Results in decreased drug detoxification</li><ul> <li>Decreased drug detoxification with higher-than-expected therapeutic drug levels
<blockquote style="color: blue; ">SER inhibition: ↓ drug metabolism</blockquote></li> </ul> </ol> </ol>
</div></html>
<html><a name="HC001015"></a> <br><a name="PB001009"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Inclusion (I)-cell disease</b> is a rare inherited condition in which there is a defect in post-translational modification of lysosomal enzymes in the Golgi membrane. Mannose residues on newly synthesized lysosomal enzymes coming from the RER are <i>not</i> phosphorylated because of a deficiency of phosphotransferase. Without mannose 6-phosphate to direct the enzymes to lysosomes, vesicles that pinch off the Golgi membrane empty the unmarked enzymes into the extracellular space where they are degraded in the blood stream. Undigested substrates (e.g., carbohydrates, lipids, and proteins) accumulate as large inclusions in the cytosol. Symptoms include psychomotor retardation and early death.</div><a name="P001016"></a><div class="PA" style="color: black; "><ol type="1"> <li>Lysosome formation and function</li><ol type="a"> <li>Hydrolytic enzymes synthesized by the rough endoplasmic reticulum (RER) are transported to the Golgi apparatus for post-translational modification.</li><li>Modification involves attaching phosphate (via phosphotransferase) to mannose residues on hydrolytic enzymes to produce mannose 6-phosphate.</li><li>The marked lysosomal enzymes attach to specific mannose 6-phosphate receptors on the Golgi membrane.
<blockquote style="color: blue; ">Primary lysosomes: derive from Golgi apparatus</blockquote></li><li>Vesicles containing the receptor-bound lysosomal enzymes pinch off the Golgi membrane to form primary lysosomes in the cytosol.</li><li>Fusion of additional vesicles to the primary lysosome further increases their content of hydrolytic enzymes.</li><li>Small vesicles containing only the receptors pinch off the primary lysosomes and return to the Golgi apparatus to bind more marked lysosomal enzymes so the cycle can repeat itself.</li><li>Lysosomal functions
<blockquote style="color: blue; ">Phagolysosome: contain lysosomal enzymes</blockquote></li><ul> <li>(1) Fusion with phagocytic vacuoles containing bacteria</li><ul> <li>These lysosomes are designated secondary or phagolysosomes.</li> </ul><li>(2) Destruction of cell organelles (autophagy; see later)</li><li>(3) Degradation of complex substrates (e.g., sphingolipids, glycosaminoglycans)</li> </ul> </ol><li>Selected lysosomal disorders</li><ol type="a"> <li>Inclusion (I)-cell disease
<blockquote style="color: blue; ">I-cell disease: defect in post-translational modification of lysosomal enzymes</blockquote></li><li>Deficiency of lysosomal enzymes involved in degradation of complex substrates characterizes the lysosomal storage diseases.
<blockquote style="color: blue; ">Lysosomal storage disease: ↓ lysosomal enzymes</blockquote></li><ul> <li>(1) Incompletely degraded complex substrates (e.g., sphingolipids, glycosaminoglycans, glycogen) accumulate in lysosomes.</li><li>(2) Example-Gaucher's disease with deficiency of glucocerebrosidase causes accumulation of glucocerebrosides in the lysosome.</li><li>(3) Example-Pompe's disease with deficiency of α-1,4-glucosidase causes an accumulation of glycogen in the lysosome.</li> </ul><li>Chédiak-Higashi syndrome (CHS)</li> </ol> </ol>
<blockquote style="color: blue; ">CHS: giant lysosomal granules; defect in formation of phagolysosomes</blockquote>
</div><a name="PB001010"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>CHS</b> is an autosomal recessive disease with a defect in a lysosomal transport protein that affects the synthesis and maintenance and storage of secretory granules in various cells (e.g., lysosomes in leukocytes, azurophilic granules in neutrophils, dense bodies in platelets). Granules in these cells tend to fuse together to become megagranules (<span>[[Fig. 1-6|Figure 1-6]]</span>). In addition, there is a defect in microtubule function in neutrophils and monocytes that prevents the fusion of lysosomes with phagosomes to produce phagolysosomes. This produces a bactericidal defect. In particular, there is increased susceptibility to developing <i>Staphylococcus aureus</i> infections. Microtubular dysfunction also produces defects in chemotaxis (directed migration), which further exacerbates the susceptibility to infection.</div></html>
<html><a name="HC001016"></a> <br><a name="P001017"></a><div class="PA" style="color: black; "><ol type="1"> <li>Normal functions of the cytoskeleton</li><ol type="a"> <li>Network of protein filaments in the cytosol</li><ul> <li>Maintains shape of the cell and, in some cases, motility of the cell</li> </ul><li>Composed of microtubules, actin filaments, intermediate filaments</li><li>Microtubules are polymers composed of the protein tubulin.</li><li>Actin thick and thin filaments are involved in the contractile process.
<blockquote style="color: blue; ">Defect tubulin synthesis G<sub>2</sub> phase: etoposide, bleomycin B</blockquote></li><li>Intermediate filaments are important in the integration of cell organelles.</li> </ol><li>Defect in synthesis of tubulin in the G<sub>2</sub> phase of the cell cycle</li><ul> <li>Etoposide and bleomycin</li> </ul><li>Mitotic spindle defects in the M phase of the cell cycle
<blockquote style="color: blue; ">Mitotic spindle defects: vinca alkaloids, colchicine, paclitaxel</blockquote></li><ol type="a"> <li>Vinca alkaloids and colchicine bind to tubulin in microtubules.</li><ul> <li>Interferes with the assembly of the mitotic spindle</li> </ul><li>Paclitaxel enhances tubulin polymerization.</li><ul> <li>Interferes with disassembly of the mitotic spindle</li> </ul> </ol><li>Intermediate filament defects</li><ol type="a"> <li>Ubiquitin, a stress protein, binds to damaged intermediate filaments.
<blockquote style="color: blue; ">Ubiquitin: marker for intermediate filament degradation</blockquote></li><ul> <li>Marks them for degradation in proteasomes and lysosomes in the cytosol</li> </ul><li>Mallory bodies</li><ul> <li>Damaged ("ubiquinated") cytokeratin intermediate filaments in hepatocytes in alcoholic liver disease (<span>[[Fig. 1-7|Figure 1-7]]</span>)</li> </ul><li>Lewy bodies</li><ul> <li>(1) Damaged neurofilaments in idiopathic Parkinson's disease</li><li>(2) Eosinophilic cytoplasmic inclusions in degenerating substantia nigra neurons</li> </ul> </ol><li>Rigor mortis</li><ul> <li>Myosin heads become locked to actin filaments as a result of a lack of ATP.</li> </ul> </ol>
</div></html>
![[1.III.A.Mitochondria]]
<<tiddler [[1.III.A.Mitochondria]]>>
![[1.III.B.Smooth endoplasmic reticulum (SER)]]
<<tiddler [[1.III.B.Smooth endoplasmic reticulum (SER)]]>>
![[1.III.C.Lysosomes]]
<<tiddler [[1.III.C.Lysosomes]]>>
![[1.III.D.Cytoskeleton]]
<<tiddler [[1.III.D.Cytoskeleton]]>>
<html><a name="HC001018"></a><span>[[Table 1-2|Table 1-2. SELECTED INTRACELLULAR ACCUMULATIONS]]</span> <br> <br> </html>
<html><a name="HC001019"></a> <br><a name="P001022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Cytosolic accumulation of triglyceride
<blockquote style="color: blue; ">Most common cause of fatty change: alcohol</blockquote></li><ul> <li>Packaged in the very low density lipoprotein (VLDL) fraction</li> </ul><li>Mechanisms of fatty change</li><ol type="a"> <li>Increased synthesis of triglyceride (TG)
<blockquote style="color: blue; ">Fatty liver: ↑ synthesis TG; ↓secretion TG</blockquote></li><ul> <li>(1) Occurs with increased conversion of dihydroxyacetone phosphate (DHAP), an intermediate of glycolysis, to glycerol 3-phosphate (G3-P)</li><ul> <li>Addition of three fatty acids (FAs) to G3-P produces TG in the liver.<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-001-g001.jpg" id=""></li> </ul><ul> <li>(a) Increased production of NADH from alcohol metabolism accelerates conversion of DHAP to G3-P.<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-001-g002.jpg" id=""></li> </ul><li>(2) Occurs with increased production of DHAP, which increases G3-P, which increases TG.</li><ul> <li>Increased intake of carbohydrates (e.g. kwashiorkor)
<blockquote style="color: blue; ">G3-P: substrate for TG synthesis</blockquote></li> </ul><li>(3) Increased availability of FAs increases synthesis of TG from G3-P; occurs with:</li><ul> <li>(a) Increased synthesis of FAs from acetyl coenzyme A (acetyl CoA)</li><ul> <li>Acetyl CoA is the end-product of alcohol metabolism (see earlier).</li> </ul><li>(b) Increased mobilization of FAs from TG stores in adipose tissue by activation of hormone sensitive lipase</li><ul> <li>Causes include alcohol and starvation.</li> </ul><li>(c) Decreased β-oxidation of FAs in the mitochondrial matrix</li><ul> <li>Causes include alcohol and diphtheria toxin, which produce mitochondrial dysfunction.</li> </ul> </ul> </ul><li>Decreased packaging of TG into VLDL and secretion of VLDL into plasma by apolipoprotein B-100</li><ul> <li>Example-decreased protein intake leading to decreased synthesis of apolipoprotein B-100 (e.g., kwashiorkor)</li> </ul> </ol><li>Morphology</li><ol type="a"> <li>Normal or enlarged liver with a yellowish discoloration</li><li>Clear space pushing the nucleus to the periphery (<span>[[Fig. 1-8|Figure 1-8]]</span>)</li> </ol><li>Fatty change may also occur in cardiac muscle.
<blockquote style="color: blue; ">Fatty change in cardiac muscle: anemia, diphtheria</blockquote></li><ol type="a"> <li>Causes</li><ul> <li>(1) Severe anemia</li><li>(2) Diphtheria</li><ul> <li>Exotoxin inhibits β-oxidation of FAs.</li> </ul> </ul><li>Heart has a mottled appearance</li><ul> <li>"Tabby cat" heart, "thrush" heart</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC001020"></a><span>[[Table 1-2|Table 1-2. SELECTED INTRACELLULAR ACCUMULATIONS]]</span> <br> <br><a name="P001023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Ferritin</li><ol type="a"> <li>Major soluble iron storage protein</li><li>Synthesized and stored in bone marrow macrophages and hepatocytes</li><li>Small amounts circulate in serum</li><ul> <li>Directly correlates with ferritin stores in the bone marrow
<blockquote style="color: blue; ">Serum ferritin: ↓ in iron deficiency anemia</blockquote></li> </ul> </ol><li>Hemosiderin</li><ol type="a"> <li>Insoluble product of ferritin degradation in lysosomes
<blockquote style="color: blue; ">Hemosiderin: ferritin degradation product</blockquote></li><li>Does <i>not</i> circulate in serum</li><li>Appears as golden brown granules in tissue</li><li>Appears as blue granules when stained with Prussian blue (see <span>[[Fig. 18-11|Figure 18-11]]</span>)</li> </ol> </ol>
</div></html>
<html><a name="HC001021"></a> <br><a name="P001024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Dystrophic calcification</li><ol type="a"> <li>Deposition of calcium phosphate in necrotic tissue
<blockquote style="color: blue; ">Dystrophic calcification: calcification of necrotic tissue</blockquote></li><li>Normal serum calcium and phosphate</li><li>Examples</li><ul> <li>(1) Calcification in chronic pancreatitis (<span>[[Fig. 1-9|Figure 1-9]]</span>)</li><li>(2) Calcified atherosclerotic plaque (see <span>[[Fig. 9-4|Figure 9-4]]</span>)</li><li>(3) Periventricular calcification in congenital cytomegalovirus infection (see <span>[[Fig. 25-24A|Figure 25-24]]</span>)</li> </ul> </ol><li>Metastatic calcification
<blockquote style="color: blue; ">Metastatic calcification: calcification of normal tissue</blockquote></li><ol type="a"> <li>Deposition of calcium phosphate in normal tissue</li><li>Due to increased serum calcium and/or phosphate</li><ul> <li>(1) Causes of hypercalcemia-primary hyperparathyroidism, malignancy-induced hypercalcemia</li><li>(2) Causes of hyperphosphatemia-renal failure, primary hypoparathyroidism</li><ul> <li>Excess phosphate drives calcium into normal tissue.</li> </ul> </ul><li>Examples of metastatic calcification</li><ul> <li>(1) Calcification of renal tubular basement membranes in the collecting ducts (nephrocalcinosis)</li><ul> <li>This can produce nephrogenic diabetes insipidus and renal failure.</li> </ul><li>(2) Basal ganglia calcification in hypoparathyroidism</li> </ul> </ol> </ol>
</div></html>
![[1.IV.A.Types of accumulations (Table 1-2)]]
<<tiddler [[1.IV.A.Types of accumulations (Table 1-2)]]>>
![[1.IV.B.Fatty change in the liver]]
<<tiddler [[1.IV.B.Fatty change in the liver]]>>
![[1.IV.C.Iron (see Table 1-2)]]
<<tiddler [[1.IV.C.Iron (see Table 1-2)]]>>
![[1.IV.D.Pathologic calcification]]
<<tiddler [[1.IV.D.Pathologic calcification]]>>
<html><a name="HC001023"></a> <br><a name="P001026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Decrease in size and weight of a tissue or organ
<blockquote style="color: blue; ">Atrophy: ↓ size/weight of tissue or organ</blockquote></li><li>Causes of atrophy</li><ol type="a"> <li>Decreased hormone stimulation</li><ul> <li>Example-hypopituitarism causing atrophy of target organs, such as the thyroid and adrenal cortex</li> </ul><li>Decreased innervation</li><ul> <li>Example-skeletal muscle atrophy following loss of lower motor neurons in amyotrophic lateral sclerosis</li> </ul><li>Decreased blood flow</li><ul> <li>Example-cerebral atrophy due to atherosclerosis of the carotid artery (<span>[[Fig. 1-10A|Figure 1-10]]</span>)</li> </ul><li>Decreased nutrients</li><ul> <li>Example-total calorie deprivation in marasmus (see <span>[[Fig. 7-1|Figure 7-1]]</span>)</li> </ul><li>Increased pressure</li><ul> <li>(1) Example-atrophy of the renal cortex and medulla in hydronephrosis (see <span>[[Fig. 19-14|Figure 19-14]]</span>)</li><li>(2) Example-thick pancreatic duct secretions in cystic fibrosis occlude the lumens causing increased luminal back-pressure and compression atrophy of the exocrine glands and tubular epithelium (<span>[[Fig. 1-10B|Figure 1-10]]</span>).</li> </ul> </ol><li>Mechanisms of atrophy</li><ol type="a"> <li>Shrinkage of cells due to increased catabolism of cell organelles (e.g., mitochondria) and reduction in cytosol
<blockquote style="color: blue; ">Atrophy: autophagic vacuoles</blockquote></li><ul> <li>(1) Organelles and cytosol form autophagic vacuoles.</li><li>(2) Autophagic vacuoles fuse with primary lysosomes for enzymatic degradation.</li><li>(3) Undigested lipids are stored as residual bodies (lipofuscin).
<blockquote style="color: blue; ">Atrophy: ↑ lipofuscin in cells</blockquote></li> </ul><li>Loss of cells by apoptosis</li> </ol> </ol>
</div><a name="PB001011"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Brown atrophy</b> is a tissue discoloration that results from lysosomal accumulation of lipofuscin ("wear and tear" pigment). Lipofuscin is an indigestible lipid derived from lipid peroxidation of cell membranes, which may occur in atrophy and free radical damage of tissue.</div></html>
![[1.V.A.Atrophy]]
<<tiddler [[1.V.A.Atrophy]]>>
![[1.V.B.Hypertrophy]]
<<tiddler [[1.V.B.Hypertrophy]]>>
![[1.V.C.Hyperplasia]]
<<tiddler [[1.V.C.Hyperplasia]]>>
![[1.V.D.Metaplasia]]
<<tiddler [[1.V.D.Metaplasia]]>>
![[1.V.E.Dysplasia]]
<<tiddler [[1.V.E.Dysplasia]]>>
<html><a name="HC001024"></a> <br><a name="P001027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Increase in cell size</li><li>Causes of hypertrophy
<blockquote style="color: blue; ">Hypertrophy: ↑ cell size; ↑ workload</blockquote></li><ol type="a"> <li>Increased workload</li><ul> <li>(1) Left ventricular hypertrophy in response to an increase in afterload (resistance) or preload (volume) (<span>[[Fig. 1-10C|Figure 1-10]]</span>)</li><li>(2) Skeletal muscle hypertrophy in weight training</li><li>(3) Smooth muscle hypertrophy in the urinary bladder in response to urethral obstruction (e.g., prostate hyperplasia)</li><li>(4) Surgical removal of one kidney with compensatory hypertrophy (and hyperplasia) of the other kidney</li> </ul><li>Cell enlargement in cytomegalovirus infections (see <span>[[Fig. 16-10B|Figure 16-10]]</span>)</li> </ol><li>Mechanisms of cardiac muscle hypertrophy</li><ol type="a"> <li>Induction of genes for synthesis of growth factors, nuclear transcription, and contractile proteins</li><li>Increase in cytosol, number of cytoplasmic organelles, and DNA content</li> </ol> </ol>
</div></html>
<html><a name="HC001025"></a> <br><a name="P001028"></a><div class="PA" style="color: black; "><ol type="1"> <li>Increase in the number of normal cells</li><li>Causes of hyperplasia
<blockquote style="color: blue; ">Hyperplasia: ↑ number of cells</blockquote></li><ol type="a"> <li>Hormone stimulation</li><ul> <li>(1) Acromegaly due to an increase in growth hormone and insulin growth factor-1 (see <span>[[Fig. 22-3|Figure 22-3]]</span>)</li><li>(2) Endometrial gland hyperplasia due to hyperestrinism (see <span>[[Fig. 21-20|Figure 21-20]]</span>)</li><ul> <li>Increased risk for developing dysplasia (see later)</li> </ul><li>(3) Benign prostatic hyperplasia due to an increase in dihydrotestosterone (<span>[[Fig. 1-10D|Figure 1-10]]</span>)</li><li>(4) Gynecomastia (male breast tissue) due to increased estrogen (see <span>[[Fig. 18-9|Figure 18-9]]</span>)</li><li>(5) Polycythemia due to an increase in erythropoietin</li> </ul><li>Chronic irritation</li><ul> <li>(1) Thickened epidermis from constant scratching</li><li>(2) Bronchial mucous gland hyperplasia in smokers and asthmatics</li><li>(3) Cirrhosis of the liver due to alcohol excess (see <span>[[Fig. 18-18|Figure 18-18]]</span>)</li> </ul><li>Chemical imbalance</li><ul> <li>(1) Hypocalcemia stimulates parathyroid gland hyperplasia</li><li>(2) Iodine deficiency produces thyroid enlargement (goiter; see <span>[[Fig. 22-12|Figure 22-12]]</span>)</li><ul> <li>Combination of hypertrophy and hyperplasia</li> </ul> </ul><li>Stimulating antibodies</li><ul> <li>Example-Graves' disease due to thyroid-stimulating antibodies (IgG) directed against thyroid-stimulating hormone receptors (see <span>[[Fig. 22-9|Figure 22-9]]</span>)</li> </ul><li>Viral infections</li><ul> <li>Example-epidermal hyperplasia (wart) due to human papillomavirus</li> </ul> </ol><li>Mechanisms of hyperplasia</li><ol type="a"> <li>Dependent on the regenerative capacity of different types of cells
<blockquote style="color: blue; ">Labile/stable cells: can divide</blockquote></li><li>Labile cells (stem cells)</li><ul> <li>(1) Divide continuously</li><li>(2) Examples-stem cells in the bone marrow, stem cells in the crypts of Lieberkühn, and basal cells in the epidermis</li><li>(3) May undergo hyperplasia as an adaptation to cell injury</li> </ul><li>Stable cells (resting cells)</li><ul> <li>(1) Divide infrequently, because they are normally in the G<sub>0</sub> (resting) phase</li><li>(2) Must be stimulated (e.g., growth factors, hormones) to enter the cell cycle</li><li>(3) Examples-hepatocytes, astrocytes, smooth muscle cells</li><li>(4) May undergo hyperplasia or hypertrophy as an adaptation to cell injury</li> </ul><li>Permanent cells (nonreplicating cells)
<blockquote style="color: blue; ">Permanent cells: cannot divide</blockquote></li><ul> <li>(1) Highly specialized cells that cannot replicate</li><li>(2) Examples-neurons and skeletal and cardiac muscle cells</li><li>(3) May undergo hypertrophy (only muscle)</li> </ul> </ol><li>Increased risk for progressing into dysplasia and cancer, in some cases (see later)</li><ul> <li>Example-endometrial hyperplasia</li> </ul> </ol>
</div></html>
<html><a name="HC001026"></a> <br><a name="P001029"></a><div class="PA" style="color: black; "><ol type="1"> <li>Replacement of one fully differentiated cell type by another</li><ul> <li>Substituted cells are less sensitive to a particular stress.
<blockquote style="color: blue; ">Metaplasia: one cell type replaces another</blockquote></li> </ul><li>Types of metaplasia</li><ol type="a"> <li>Metaplasia from squamous to glandular epithelium</li><ul> <li>(1) Example-distal esophagus epithelium shows an increase in goblet cells and mucus-secreting cells in response to acid reflux (<span>[[Fig. 1-10E|Figure 1-10]]</span>)</li><li>(2) This is called Barrett's esophagus.
<blockquote style="color: blue; ">Barrett's esophagus: glandular metaplasia, gastric reflux</blockquote></li><ul> <li>Increased risk for developing dysplasia (see later)</li> </ul> </ul><li>Metaplasia from glandular to other types of glandular epithelium</li><ul> <li>(1) Example-pylorus and antrum epithelium shows an increase in goblet cells and Paneth cells in response to <i>Helicobacter pylori</i>-induced chronic atrophic gastritis</li><li>(2) This is called intestinal metaplasia (see <span>[[Fig. 17-14|Figure 17-14]]</span>).</li><ul> <li>Increased risk for developing dysplasia (see later)</li> </ul> </ul><li>Metaplasia from glandular to squamous epithelium</li><ul> <li>(1) Mainstem bronchus epithelium develops squamous metaplasia in response to irritants in cigarette smoke (<span>[[Fig. 1-10F|Figure 1-10]]</span>).</li><li>(2) Endocervical epithelium develops squamous metaplasia in response to the acid pH in the vagina.
<blockquote style="color: blue; ">Metaplasia/hyperplasia: in some cases, may progress to dysplasia</blockquote></li><li>(3) Both of the above alterations have an increased risk for developing dysplasia (see later).</li> </ul><li>Metaplasia from transitional to squamous epithelium</li><ul> <li>(1) <i>Schistosoma hematobium</i> infection in the urinary bladder causes transitional epithelium to undergo squamous metaplasia.</li><li>(2) Increased risk for developing dysplasia (see later)</li> </ul> </ol><li>Mechanism of metaplasia</li><ol type="a"> <li>Stem cells have an array of progeny cells that have different patterns of gene expression.</li><ul> <li>Under normal physiologic conditions differentiation of these progeny cells is restricted.</li> </ul><li>Metaplasia may result from reprogramming stem cells to utilize progeny cells with a different pattern of gene expression; the following signals may initiate this change:</li><ul> <li>(1) Hormones (e.g., estrogen)</li><li>(2) Vitamins (e.g., retinoic acid)</li><li>(3) Chemical irritants (e.g., cigarette smoke)</li> </ul><li>Metaplasia is sometimes reversible if the irritant is removed.</li> </ol> </ol>
</div></html>
<html><a name="HC001027"></a> <br><a name="P001030"></a><div class="PA" style="color: black; "><ol type="1"> <li>Disordered cell growth</li><ul> <li>Precursor to cancer
<blockquote style="color: blue; ">Dysplasia: disordered cell growth</blockquote></li> </ul><li>Risk factors for dysplasia</li><ol type="a"> <li>Some types of hyperplasia (see section V)</li><li>Some types of metaplasia (see section V)</li><li>Infection</li><ul> <li>Example-human papillomavirus type 16, causing squamous dysplasia of the cervix</li> </ul><li>Chemicals</li><ul> <li>Example-irritants in cigarette smoke, causing squamous metaplasia to progress to squamous dysplasia in the mainstem bronchus</li> </ul><li>Ultraviolet light</li><ul> <li>Example-solar damage of the skin, causing squamous dysplasia</li> </ul><li>Chronic irritation of skin</li><ul> <li>Example-draining sinus tracts in osteomyelitis
<blockquote style="color: blue; ">Dysplasia may progress to cancer.</blockquote></li> </ul> </ol><li>Microscopic features of dysplasia (<span>[[Fig. 1-10G|Figure 1-10]]</span>)</li><ol type="a"> <li>Nuclear features</li><ul> <li>(1) Increased mitotic activity, with normal mitotic spindles</li><li>(2) Increased nuclear size and chromatin</li> </ul><li>Disorderly proliferation of cells with loss of cell maturation as cells progress to the surface</li> </ol><li>Dysplasia is sometimes reversible if the irritant is removed.</li> </ol>
</div></html>
<html><a name="HC001029"></a> <br><a name="PB001012"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Dry gangrene</b> of the toes in individuals with diabetes mellitus is a form of infarction that results from ischemia. Coagulation necrosis is the primary type of necrosis that is present in the dead tissue (<span>[[Fig. 1-11D|Figure 1-11]]</span>).</div><a name="PB001013"></a><div class="BB" style="color: rgb(47, 79, 79); ">Dry gangrene of the toes with a superimposed anaerobic infection (e.g., <i>Clostridium perfringens</i>) leads to acute inflammation, where liquefactive necrosis is the primary type of necrosis. This condition is called wet gangrene (<span>[[Fig. 1-11F|Figure 1-11]]</span>).</div><a name="P001033"></a><div class="PA" style="color: black; "><ol type="1"> <li>Death of groups of cells, often accompanied by an inflammatory infiltrate</li><li>Coagulation necrosis</li><ol type="a"> <li>Preservation of the structural outline of dead cells
<blockquote style="color: blue; ">Coagulation necrosis: preservation of structural outlines</blockquote></li><li>Mechanism of coagulation necrosis</li><ul> <li>(1) Denaturation of enzymes and structural proteins</li><ul> <li>(a) Intracellular accumulation of lactate or heavy metals (e.g., lead, mercury)</li><li>(b) Exposure of cells to ionizing radiation</li> </ul><li>(2) Inactivation of intracellular enzymes prevents dissolution (autolysis) of the cell.</li> </ul><li>Microscopic features (<span>[[Fig. 1-11A|Figure 1-11]]</span>)</li><ul> <li>(1) Indistinct outlines of cells within dead tissue</li><li>(2) Absent nuclei or karyolysis (fading of nuclear chromatin)</li> </ul><li>Infarction</li><ul> <li>(1) Gross manifestation of coagulation necrosis secondary to the sudden occlusion of a vessel
<blockquote style="color: blue; ">Infarctions: pale and hemorrhagic types</blockquote></li><li>(2) Usually wedge-shaped if dichotomously branching vessels (e.g., pulmonary artery) are occluded</li><li>(3) Pale (ischemic) type</li><ul> <li>Increased density of tissue (e.g., heart, kidney, spleen) prevents RBCs from diffusing through necrotic tissue (<span>[[Fig. 1-11B|Figure 1-11]]</span>).</li> </ul><li>(4) Hemorrhagic (red) type</li><ul> <li>Loose-textured tissue (e.g., lungs, small bowel) allows RBCs to diffuse through necrotic tissue (<span>[[Fig. 1-11C|Figure 1-11]]</span>).
<blockquote style="color: blue; ">Dry gangrene: predominantly coagulation necrosis</blockquote></li> </ul> </ul><li>Factors influencing whether an infarction will occur in tissue</li><ul> <li>(1) Size of the vessel that is occluded</li><ul> <li>(a) Infarction is unlikely with obstruction of a major branch of a pulmonary artery.</li><li>(b) Infarction is likely if a thrombus overlies an atherosclerotic plaque in a coronary artery.</li> </ul><li>(2) State of development of a collateral circulation</li><ul> <li>Infarction is <i>less</i> likely if a well-developed collateral circulation is present (e.g., arcade system of the superior and inferior mesenteric arteries).</li> </ul><li>(3) Presence of a dual blood supply</li><ul> <li>(a) Infarction is <i>less</i> likely if a dual blood supply is present (e.g., pulmonary and bronchial arteries in the lungs).</li><li>(b) Renal and splenic arteries have end-arteries with an inadequate network of anastomosing vessels beyond potential points of obstruction; hence, infarction is likely to occur.
<blockquote style="color: blue; ">Infarction less likely: dual blood supply, collateral circulation</blockquote></li> </ul><li>(4) Sudden onset of ischemia in an organ with preexisting disease will more likely produce an infarction.</li><ul> <li>Example-a pulmonary embolus will more likely produce an infarction in a patient with preexisting chronic lung or heart disease.</li> </ul><li>(5) Tissues with a high O<sub>2</sub> requirement (e.g., brain, heart) are more likely to infarct than other less sensitive tissues (e.g., muscle, cartilage).</li><li>(6) Rapidity with which a vessel is occluded often determines whether an infarction will occur.</li><ul> <li>(a) Slow occlusion often allows time for development of a collateral circulation.</li><li>(b) Abrupt occlusion often results in infarction.</li> </ul> </ul> </ol><li>Liquefactive necrosis</li><ol type="a"> <li>Necrotic degradation of tissue that softens and becomes liquefied</li><li>Mechanisms</li><ul> <li>Lysosomal enzymes released by necrotic cells or neutrophils cause liquefaction of tissue.</li> </ul><li>Examples
<blockquote style="color: blue; ">Cerebral infarction: liquefactive <i>not</i> coagulative necrosis</blockquote></li><ul> <li>(1) Central nervous system infarction</li><ul> <li>Autocatalytic effect of hydrolytic enzymes generated by neuroglial cells produces a cystic space (<span>[[Fig. 1-11E|Figure 1-11]]</span>).</li> </ul><li>(2) Abscess in a bacterial infection</li><ul> <li>Hydrolytic enzymes generated by neutrophils liquefy dead tissue.
<blockquote style="color: blue; ">Wet gangrene: predominantly liquefactive necrosis</blockquote></li> </ul> </ul> </ol><li>Caseous necrosis</li><ol type="a"> <li>Variant of coagulation necrosis</li><ul> <li>Associated with acellular, cheese-like (caseous) material</li> </ul><li>Mechanism</li><ul> <li>(1) Caseous material is formed by the release of lipid from the cell walls of <i>Mycobacterium tuberculosis</i> and systemic fungi (e.g., <i>Histoplasma</i>) after immune destruction by macrophages.</li><li>(2) Other diseases associated with granuloma formation do <i>not</i> exhibit caseation.</li><ul> <li>Examples-Crohn disease, sarcoidosis, foreign body giant cell reaction
<blockquote style="color: blue; ">Tuberculosis: most common cause of caseous necrosis</blockquote></li> </ul> </ul><li>Microscopic features of a granuloma</li><ul> <li>Acellular material in the center surrounded by activated macrophages, CD4 helper T cells, and multinucleated giant cells (<span>[[Fig. 1-11G|Figure 1-11]]</span>)</li> </ul> </ol><li>Enzymatic fat necrosis</li><ol type="a"> <li>Peculiar to adipose tissue located around an acutely inflamed pancreas
<blockquote style="color: blue; ">Enzymatic fat necrosis: acute pancreatitis</blockquote></li><li>Mechanisms</li><ul> <li>(1) Activation of pancreatic lipase (e.g., alcohol excess) causing hydrolysis of triglyceride in fat cells with release of fatty acids</li><li>(2) Conversion of fatty acids into soap (saponification)</li><ul> <li>Combination of fatty acids and calcium</li> </ul> </ul><li>Gross appearance</li><ul> <li>Chalky yellow-white deposits are primarily located in peripancreatic and omental adipose tissue (<span>[[Fig. 1-11H|Figure 1-11]]</span>).</li> </ul><li>Microscopic appearance</li><ul> <li>Pale outlines of fat cells filled with basophilic-staining calcified areas</li> </ul> </ol><li>Traumatic fat necrosis
<blockquote style="color: blue; ">Traumatic fat necrosis: not enzyme-mediated</blockquote></li><ol type="a"> <li>Occurs in fatty tissue (e.g., female breast tissue) as a result of trauma</li><li><i>Not</i> enzyme-mediated</li> </ol><li>Fibrinoid necrosis</li><ol type="a"> <li>Limited to small muscular arteries, arterioles, venules, and glomerular capillaries
<blockquote style="color: blue; ">Fibrinoid necrosis: necrosis of immune-mediated disease</blockquote></li><li>Mechanism</li><ul> <li>Deposition of pink-staining proteinaceous material in damaged vessel walls due to damaged basement membranes</li> </ul><li>Associated conditions</li><ul> <li>Immune vasculitis (e.g., Henoch-Schönlein purpura), malignant hypertension</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC001030"></a> <br><a name="P001034"></a><div class="PA" style="color: black; "><ol type="1"> <li>Programmed, enzyme-mediated cell death
<blockquote style="color: blue; ">Apoptosis: programmed cell death</blockquote></li><li>Normal and pathologic processes associated with apoptosis</li><ol type="a"> <li>Destruction of cells during embryogenesis</li><ul> <li>Example-loss of müllerian structures in a male fetus due to Sertoli cell synthesis of müllerian inhibitory factor</li> </ul><li>Hormone-dependent atrophy of tissue</li><ul> <li>Example-endometrial cell breakdown after withdrawal of estrogen and progesterone in the menstrual cycle</li> </ul><li>Death of tumor cells and virus infected cells by cytotoxic CD8 T cells</li><li>Corticosteroid destruction of lymphocytes (B and T cells)</li><li>Removal of acute inflammatory cells (e.g., neutrophils) from healing sites</li><li>Damage to DNA by radiation, FRs, toxins</li><li>Removal of misfolded proteins</li><ul> <li>Examples-amyloid, β-amyloid protein, proteins in prion-related disease (Creutzfeldt-Jakob disease)</li> </ul> </ol><li>Mechanisms of apoptosis
<blockquote style="color: blue; ">Extrinsic pathway of apoptosis: requires TNF</blockquote></li><ol type="a"> <li>Extrinsic pathway</li><ul> <li>(1) Binding of tumor necrosis factor (TNF) to its receptor</li><li>(2) Eventual activation of caspases (see later)</li> </ul><li>Intrinsic pathway</li><ul> <li>(1) Mitochondrial leakage of cytochrome <i>c</i> into the cytosol</li><li>(2) Eventual activation of caspases (see later)</li> </ul><li>Genes regulating apoptosis via the intrinsic pathway</li><ul> <li>(1) <i>BCL2</i> gene family</li><ul> <li>Located on chromosome 18</li> </ul><ul> <li>(a) Manufactures gene products that inhibit apoptosis (i.e., antiapoptosis gene)
<blockquote style="color: blue; "><i>BCL2</i> gene: antiapoptosis gene</blockquote></li><li>(b) Gene products prevent mitochondrial leakage of cytochrome <i>c</i> into the cytosol.</li> </ul><li>(2) <i>TP53</i> suppressor gene
<blockquote style="color: blue; "><i>TP53</i> suppressor gene: "guardian" of the cell</blockquote></li><ul> <li>(a) Temporarily arrests the cell cycle in the G<sub>1</sub> phase to repair DNA damage (aborts apoptosis)</li><li>(b) Promotes apoptosis if DNA damage is too great by activating the <i>BAX</i> apoptosis gene</li><ul> <li><i>BAX</i> gene products inactivate the <i>BCL2</i> antiapoptosis gene.
<blockquote style="color: blue; "><i>BAX</i> gene: apoptosis gene</blockquote></li> </ul> </ul> </ul><li>Caspases
<blockquote style="color: blue; ">Caspases: group of cysteine proteases; activation induces apoptosis</blockquote></li><ul> <li>(1) Group of inactive proenzymes (proteases, endonucleases)</li><ul> <li>Must be activated by the extrinsic or intrinsic system to produce apoptosis</li> </ul><li>(2) Changes in the cell</li><li>(3) Activation of endonuclease leads to nuclear pyknosis ("ink dot" appearance) and fragmentation.</li><li>(4) Activation of protease leads to breakdown of the cytoskeleton.</li><li>(5) Formation of cytoplasmic buds on the cell membrane</li><ul> <li>Buds contain nuclear fragments, mitochondria, and condensed protein fragments.</li> </ul><li>(6) Formation of apoptotic bodies by the breaking off of cytoplasmic buds</li><li>(7) Phagocytosis of apoptotic bodies by neighboring cells or macrophages</li> </ul> </ol><li>Microscopic appearance of apoptosis
<blockquote style="color: blue; ">Apoptosis: deeply eosinophilic cytoplasm; pyknotic nucleus</blockquote></li><ol type="a"> <li>Cell detachment from neighboring cells</li><li>Deeply eosinophilic-staining cytoplasm (<span>[[Fig. 1-12|Figure 1-12]]</span>)</li><li>Pyknotic, fragmented, or absent nucleus</li><li>Minimal or no inflammatory infiltrate surrounding the cell</li> </ol> </ol>
</div></html>
<html><a name="HC001031"></a><span>[[Box 1-1|BOX 1-1 CLINICAL ENZYMOLOGY]]</span> <br> <br><a name="B001001"></a><div class="BT">BOX 1-1 CLINICAL ENZYMOLOGY</div><a name="PB001014"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Enzymes</b> are protein catalysts of biologic origin that increase the rate of chemical reactions without themselves being consumed or structurally altered. <b>Isoenzymes</b> (isozymes) are multiple forms of the same enzyme that differ in stereotypical, biochemical, and immunologic properties (e.g., lactate dehydrogenase isoenzymes L<sub>1</sub>-L<sub>5</sub>; creatine kinase isoenzymes MM, MB, and BB). Measurement of individual isoenzymes is frequently more specific in identifying a disease than is total enzyme activity (e.g., CK-MB isoenzyme in identifying an acute myocardial infarction). <b>Isoforms</b> are subtypes of the individual isoenzymes (e.g., CK-MM isoforms).</div><a name="PB001015"></a><div class="BB" style="color: rgb(47, 79, 79); ">Enzymes distribute in cell membranes (e.g., alkaline phosphatase), endoplasmic reticulum (e.g., γ-glutamyltransferase), lysosomes (e.g., muramidase), zymogen (e.g., amylase), cytoplasm (e.g., alanine aminotransferase, a transaminase), and mitochondria (e.g., aspartate aminotransferase, a transaminase).</div><a name="PB001016"></a><div class="BB" style="color: rgb(47, 79, 79); ">Factors influencing the release of enzymes into body fluids include disruption or damage to the cell membrane (e.g., alanine aminotransferase, CK), increased synthesis owing to regeneration of injured cells (e.g., alkaline phosphatase), and enzyme induction in the smooth endoplasmic reticulum by drugs (e.g., alcohol and its effect on increasing γ-glutamyltransferase synthesis).</div><a name="PB001017"></a><div class="BB" style="color: rgb(47, 79, 79); ">The amount of enzyme released into body fluids depends on the amount of tissue injury, the rate of diffusion out of the damaged cell, and the overall rate of catabolism or clearance of the enzyme. The following table lists important enzymes that are increased in tissue injury.</div></html>
![[1.VI.A.Necrosis]]
<<tiddler [[1.VI.A.Necrosis]]>>
![[1.VI.B.Apoptosis]]
<<tiddler [[1.VI.B.Apoptosis]]>>
![[1.VI.C.Enzyme markers of cell death (Box 1-1)]]
<<tiddler [[1.VI.C.Enzyme markers of cell death (Box 1-1)]]>>
<html><a name="HC010001"></a><span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span> <br> <br> </html>
![[10.I.A.Cardiac Physical Diagnosis (Box 10-1)]]
<<tiddler [[10.I.A.Cardiac Physical Diagnosis (Box 10-1)]]>>
<html><a name="HC010003"></a> <br><a name="P010002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sustained pressure in the ventricles increases wall stress.</li><li>Changes in wall stress produce changes in gene expression.
<blockquote style="color: blue; ">Wall stress increases gene-controlled sarcomere duplication.</blockquote></li><li>Changes in gene expression lead to duplication of sarcomeres.</li><ul> <li>Sarcomeres are the contractile element of muscle.</li> </ul><li>Changes in wall stress related to an increase in afterload</li><ol type="a"> <li>Afterload is the resistance the ventricle contracts against to eject blood in systole.
<blockquote style="color: blue; ">Afterload: resistance ventricle contracts against to eject blood in systole</blockquote></li><li>Increased afterload produces concentric thickening of the ventricular wall (<span>[[Fig. 10-1A|Figure 10-1]]</span>).</li><ul> <li>Sarcomeres duplicate parallel to the long axes of the cells; muscles are thicker.</li> </ul><li>Causes of concentric left ventricular hypertrophy (LVH)</li><ul> <li>(1) Essential hypertension (most common)</li><li>(2) Aortic stenosis</li><li>(3) Hypertrophic cardiomyopathy
<blockquote style="color: blue; ">Ventricular hypertrophy: increased afterload causes concentric hypertrophy</blockquote></li> </ul><li>Causes of concentric right ventricular hypertrophy (RVH)</li><ul> <li>(1) Pulmonary hypertension</li><li>(2) Pulmonary artery stenosis</li> </ul> </ol><li>Changes in wall stress related to increased preload
<blockquote style="color: blue; ">Preload: equivalent to LVEDV</blockquote></li><ol type="a"> <li>Preload correlates with left ventricular end-diastolic volume (LVEDV).</li><li>Increased preload invokes the Frank-Starling pressure relationship to increase stroke volume.
<blockquote style="color: blue; ">Ventricular hypertrophy: increased preload causes eccentric hypertrophy</blockquote></li><li>Increased preload causes dilation and hypertrophy (eccentric hypertrophy) of ventricular wall (<span>[[Fig. 10-1B|Figure 10-1]]</span>).</li><ul> <li>Sarcomeres duplicate in series; muscle length and width are increased.</li> </ul><li>Causes of eccentric hypertrophy of the left ventricle</li><ul> <li>(1) Mitral valve or aortic valve regurgitation</li><li>(2) Left-to-right shunting of blood (e.g., ventricular septal defect)</li><ul> <li>More blood returns to the left side of the heart.</li> </ul> </ul><li>Causes of eccentric hypertrophy of the right ventricle</li><ul> <li>Tricuspid valve or pulmonary valve regurgitation</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC010004"></a> <br><a name="P010003"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Consequences of hypertrophy: heart failure, S<sub>4</sub>, angina (LVH)</blockquote>
<ol type="1"> <li>Left- and right-sided heart failure</li><li>Angina (primarily LVH)</li><li>S<sub>4</sub> heart sound (see <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>)</li><ol type="a"> <li>Correlates with atrial contraction in late diastole; atrial gallop (see <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>)</li><li>Caused by blood entering a noncompliant ventricle
<blockquote style="color: blue; ">S<sub>4</sub>: blood entering noncompliant ventricle</blockquote></li><li>Examples</li><ul> <li>(1) Concentric LVH in essential hypertension or aortic stenosis</li><li>(2) Concentric RVH in pulmonary hypertension or pulmonary stenosis</li><li>(3) Volume overload in mitral regurgitation or tricuspid regurgitation</li><li>(4) Volume overload in aortic regurgitation or pulmonary regurgitation</li> </ul> </ol> </ol>
</div></html>
![[10.II.A.Pathogenesis of left and right ventricular hypertrophy]]
<<tiddler [[10.II.A.Pathogenesis of left and right ventricular hypertrophy]]>>
![[10.II.B.Consequences of ventricular hypertrophy]]
<<tiddler [[10.II.B.Consequences of ventricular hypertrophy]]>>
<html><a name="HC010006"></a> <br><a name="P010005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common hospital admission diagnosis in elderly patients</li><li>Types of CHF</li><ol type="a"> <li>Left-sided heart failure (most common type)</li><li>Right-sided heart failure</li><li>Biventricular heart failure (left- and right-sided heart failure)</li><li>High-output heart failure (least common type)</li> </ol> </ol>
</div></html>
<html><a name="HC010007"></a> <br><a name="PB010001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Systolic dysfunction</b> is characterized by a low ejection fraction (EF) (<40%). The EF equals the stroke volume divided by the left ventricular end-diastolic volume. The normal value ranges from 55% to 80%. <b>Diastolic dysfunction</b> is characterized by normal to high EF (stiff ventricle) and an S<sub>4</sub> atrial gallop due to increased resistance to filling in late diastole. There is an increase in left atrial pressure and pulmonary congestion. If left ventricular filling is significantly impaired, cardiac output is decreased.</div><a name="P010006"></a><div class="PA" style="color: black; "><ol type="1"> <li>Forward failure
<blockquote style="color: blue; ">Left-sided heart failure = forward failure → pulmonary edema</blockquote></li><ol type="a"> <li>Left ventricle cannot efficiently eject blood into the aorta.</li><li>Causes an increase in left ventricular end-diastolic volume (LVEDV) and pressure (LVEDP).</li><li>Increased volume and pressure causes backup of blood into the lungs producing pulmonary edema.</li><ul> <li>In LHF blood builds up behind the failed heart.</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Decreased ventricular contraction (systolic dysfunction)
<blockquote style="color: blue; ">Systolic dysfunction: most common type of LHF</blockquote></li><ul> <li>(1) Most common type of LHF</li><li>(2) Causes of systolic dysfunction</li><ul> <li>(a) Ischemia due to coronary artery atherosclerosis (most common cause)</li><li>(b) Post-myocardial infarction, myocardial fibrosis, myocarditis, dilated cardiomyopathy</li> </ul> </ul><li>Noncompliant ventricle (diastolic dysfunction)</li><ul> <li>(1) Restricted filling of the left ventricle in diastole</li><li>(2) Causes of diastolic dysfunction
<blockquote style="color: blue; ">Diastolic dysfunction: most common cause is hypertension</blockquote></li><ul> <li>(a) Concentric LVH due to essential hypertension is the most common cause.</li><ul> <li>Other causes include aortic stenosis, hypertrophic cardiomyopathy.</li> </ul><li>(b) Infiltration of muscle with amyloid, glycogen (restrictive cardiomyopathies)</li><li>(c) Left ventricular volume overload due to aortic/mitral regurgitation</li><ul> <li>Ventricular distention restricts filling in diastole.</li> </ul> </ul> </ul> </ol><li>Gross and microscopic findings
<blockquote style="color: blue; ">Systolic dysfunction: ↓ ventricular contraction; ↓ EF</blockquote>
<blockquote style="color: blue; ">Diastolic dysfunction: ↑ resistance to filling the ventricle; normal EF</blockquote></li><ol type="a"> <li>Lungs are heavy, congested, and exude a frothy pink transudate (edema).</li><li>Alveolar macrophages contain hemosiderin ("heart failure" cells).</li> </ol><li>Clinical and laboratory findings</li><ol type="a"> <li>Difficulty with breathing (dyspnea)</li><ul> <li>(1) Patient cannot take a full inspiration.
<blockquote style="color: blue; ">Dyspnea: cannot take full inspiration</blockquote></li><li>(2) Caused by interstitial fluid stimulating juxtacapillary J receptors innervated by the vagus nerve</li> </ul><li>Pulmonary edema</li><ul> <li>(1) Increase in LVEDV increases hydrostatic pressure in the left ventricle, left atrium, pulmonary vein, and pulmonary capillaries which overrides the pulmonary capillary oncotic pressure (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>).
<blockquote style="color: blue; ">Pulmonary edema: hydrostatic pressure > oncotic pressure</blockquote></li><ul> <li>(a) A transudate initially leaks into the interstitial space producing dyspnea and then moves into the alveoli producing pulmonary edema.</li><li>(b) Septal edema produces Kerley's lines in a chest radiograph.
<blockquote style="color: blue; ">Kerley's lines: septal edema</blockquote></li><li>(c) Peribronchiolar edema produces expiratory wheezing (called cardiac asthma).</li> </ul><li>(2) Bibasilar inspiratory crackles</li><ul> <li>Crackles are due to air expanding alveoli filled with fluid.</li> </ul><li>(3) Rupture of pulmonary capillaries may occur from increased hydrostatic pressure.</li><ul> <li>(a) Blood is phagocytosed by alveolar macrophages.
<blockquote style="color: blue; ">Heart failure cells: alveolar macrophages with hemosiderin</blockquote></li><li>(b) Hemosiderin accumulates in alveolar macrophages (called heart failure cells).</li><ul> <li>Sputum has a rusty color.</li> </ul> </ul><li>(4) Chest radiograph findings in pulmonary edema</li><ul> <li>(a) Congestion in upper lobes (early finding)</li><li>(b) Perihilar congestion ("bat wing configuration")</li><li>(c) Alveolar infiltrates (<span>[[Fig. 10-2|Figure 10-2]]</span>)</li> </ul> </ul><li>Left-sided S<sub>3</sub> heart sound (see <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>)
<blockquote style="color: blue; ">S<sub>3</sub> heart sound: first cardiac sign of LHF</blockquote></li><li>Functional mitral valve (MV) regurgitation</li><ul> <li>Caused by stretching of the MV ring</li> </ul><li>Paroxysmal nocturnal dyspnea (PND)</li><ul> <li>(1) PND refers to a choking sensation that occurs at night when the patient is supine.</li><li>(2) Without the effect of gravity, fluid from the interstitial space moves into the vascular compartment.</li><li>(3) This increases venous return to the right side of the heart and then to the failed left side of the heart.
<blockquote style="color: blue; ">PND/orthopnea: ↑ venous return to right side of the heart at night</blockquote></li><li>(4) The failed left side of the heart cannot handle the excess load and blood backs up into the lungs, producing pulmonary edema.</li><li>(5) Dyspnea is relieved by standing or placing pillows under the head (pillow orthopnea).</li><ul> <li>Raising the head on pillows increases the effect of gravity on reducing venous return to the heart.</li> </ul> </ul><li>Increased serum brain natriuretic peptide (BNP)
<blockquote style="color: blue; ">BNP: useful in confirming/excluding LHF</blockquote></li><ul> <li>(1) Cardiac neurohormone secreted from the ventricles (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li><li>(2) Secreted in response to volume expansion and pressure overload in the ventricle</li><li>(3) Clinical usefulness</li><ul> <li>(a) Diagnosing LHF (increased)</li><li>(b) Excluding LHF (normal)</li><li>(c) Predictor of survival</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC010008"></a> <br><a name="PB010002"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Nonpharmacologic therapy</b> in congestive heart failure involves restricting sodium (<2 g/day) and water (<2 L/day), both of which are increased due to the decreased cardiac output and renal retention of sodium and water (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>). Systolic dysfunction is treated with drugs that reduce the workload of the left ventricle. This is accomplished by decreasing afterload and preload. A mainstay of treatment for systolic dysfunction are the angiotensin-converting enzyme (ACE) inhibitors or receptor inhibitors if patients develop chronic cough. ACE inhibitors decrease afterload by decreasing angiotensin II and decrease preload by decreasing aldosterone. Diuretics (e.g., loop diuretics, aldosterone blockers) complement ACE inhibitors by decreasing preload. β-Blockers decrease sympathetic tone, which reduces myocardial O<sub>2</sub> consumption. Digitalis may be useful because of its inotropic and vagotonic effects particularly in severe heart failure or those with atrial arrhythmias. Direct vasodilating drugs (e.g., hydralazine) reduce systemic vascular resistance and pulmonary venous pressure. Therapeutic options for treating diastolic dysfunction are based on the cause of diastolic dysfunction. If hypertension is the primary cause, calcium channel blockers, ACE inhibitors, and β-blockers are used, the latter decreasing heart rate, which prolongs diastolic filling. Diuretics must be used with caution, because excessive diuresis may produce volume depletion and decrease the cardiac output.</div><a name="P010007"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">RHF = backward failure → increase in venous hydrostatic pressure</blockquote>
<ol type="1"> <li>Backward failure</li><ol type="a"> <li>Right side of the heart cannot pump blood from the venous system into the lungs.</li><li>Blood accumulates under pressure in the venous system.</li><ul> <li>In RHF, blood builds up behind the failed heart.</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Decreased contraction</li><ul> <li>Example-right ventricular infarction</li> </ul><li>Noncompliant right ventricle</li><ul> <li>Example-right ventricular hypertrophy</li> </ul><li>Increased afterload</li><ul> <li>Examples-LHF (most common cause), pulmonary hypertension</li> </ul><li>Increased preload</li><ul> <li>Examples-tricuspid valve regurgitation, left-to-right shunt
<blockquote style="color: blue; ">RHF: most common cause of LHF</blockquote></li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Prominence of the jugular veins (<span>[[Fig. 10-3|Figure 10-3]]</span>)</li><ul> <li>Due to increased venous hydrostatic pressure
<blockquote style="color: blue; ">RHF: ↑ venous hydrostatic pressure</blockquote></li> </ul><li>Functional tricuspid valve (TV) regurgitation</li><ul> <li>Caused by stretching of the TV ring from volume overload</li> </ul><li>Right-sided S<sub>3</sub> and S<sub>4</sub> heart sounds</li><ul> <li>Both are due to volume overload in the ventricle.</li> </ul><li>Painful hepatomegaly</li><ul> <li>(1) Due to passive liver congestion</li><ul> <li>Backup of venous blood into the hepatic veins and then into the central veins (see <span>[[Fig. 18-5|Figure 18-5]]</span>)</li> </ul><li>(2) Increase in portal vein pressure may lead to ascites.</li><li>(3) Compression of the congested liver produces jugular neck vein distention (hepatojugular reflux).</li> </ul><li>Dependent pitting edema (see <span>[[Fig. 4-4|Figure 4-4]]</span>)
<blockquote style="color: blue; ">RHF: neck vein distention, hepatomegaly, dependent pitting edema, ascites</blockquote></li><ul> <li>Due to an increase in venous hydrostatic pressure</li> </ul><li>Cyanosis of mucous membranes</li><ul> <li>(1) More likely to occur in RHF than LHF</li><li>(2) Increased time for peripheral tissue to extract O<sub>2</sub>; hence, decreasing O<sub>2</sub> saturation (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li> </ul> </ol> </ol>
</div></html>
![[10.III.A.Epidemiology]]
<<tiddler [[10.III.A.Epidemiology]]>>
![[10.III.B.Left-sided heart failure (LHF)]]
<<tiddler [[10.III.B.Left-sided heart failure (LHF)]]>>
![[10.III.C.Right-sided heart failure (RHF)]]
<<tiddler [[10.III.C.Right-sided heart failure (RHF)]]>>
![[10.III.D.High-output heart failure]]
<<tiddler [[10.III.D.High-output heart failure]]>>
<html><a name="HC010009"></a> <br><a name="P010008"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">ACE inhibitors: ↓ afterload, ↓ preload</blockquote>
<blockquote style="color: blue; ">β-Blockers: ↓ myocardial O<sub>2</sub> consumption; ↓ heart rate</blockquote>
<ol type="1"> <li>Definition</li><ul> <li>Form of heart failure in which cardiac output is increased compared with values for the normal resting state</li> </ul><li>Pathogenesis</li><ol type="a"> <li>Increase in stroke volume (SV)</li><ul> <li>Example-hyperthyroidism</li> </ul><li>Decrease in blood viscosity</li><ul> <li>(1) Decreases total peripheral resistance (TPR)</li><li>(2) Increases venous return to the heart.</li><li>(3) Example-severe anemia</li> </ul><li>Vasodilation of peripheral resistance arterioles</li><ul> <li>(1) Increases venous return to the heart</li><li>(2) Examples-thiamine deficiency (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>), early phase of endotoxic shock (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li> </ul><li>Arteriovenous fistula</li><ul> <li>(1) Arteriovenous communications bypass the microcirculation.</li><li>(2) Increases venous return to the heart</li><li>(3) Causes of arteriovenous fistulas</li><ul> <li>(a) Trauma from a knife wound (most common cause)
<blockquote style="color: blue; ">High output failure: ↑ SV, ↓ TPR, arteriovenous fistula</blockquote></li><li>(b) Surgical shunt for hemodialysis</li><li>(c) Mosaic bone in Paget's disease (refer to <span macro="tag [[23 Musculoskeletal and Soft Tissue Disorders]] [[Chapter 23]]"></span>)</li> </ul> </ul> </ol> </ol>
</div><a name="B010001"></a><div class="BT">BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS</div><a name="PB010003"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Valve Locations for Auscultation</b></div><a name="PB010004"></a><div class="BB" style="color: rgb(47, 79, 79); ">Locations where heart sounds are best heard do <i>not</i> always correlate with their anatomic location. The mitral valve (MV) is best heard at the apex; the tricuspid valve (TV) at the left parasternal border; the pulmonary valve (PV) at the left second and third intercostal spaces (ICS); and the aortic valve (AV) at the left sternal border for regurgitation murmurs and right second ICS for ejection murmurs.</div><a name="PB010005"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Cardiac Cycle Relationships with Heart Sounds</b></div><a name="PB010006"></a><div class="BB" style="color: rgb(47, 79, 79); ">The P wave represents atrial depolarization; the PR interval atrioventricular conduction time; the QRS ventricular depolarization; and the T wave ventricular repolarization, or recovery. The S<sub>1</sub> heart sound occurs at the same time as the QRS complex and marks the beginning of systole, while the S<sub>2</sub> heart sound occurs after the T wave and marks the beginning of diastole.</div><a name="PB010007"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Heart Sounds</b></div><a name="PB010008"></a><div class="BB" style="color: rgb(47, 79, 79); ">The <b>S<sub>1</sub> heart sound</b> corresponds with closure of the MV and TV during systole. The MV closes <i>before</i> the TV. It is best heard at the apex and corresponds with the carotid/radial pulse. The <b>S<sub>2</sub> heart sound</b> is caused by closure of the AV and PV and marks the beginning of diastole. It is best heard at the left second or third ICS. The aortic component (A<sub>2</sub>) normally precedes the pulmonary component (P<sub>2</sub>). Unlike the S<sub>1</sub> heart sound, the S<sub>2</sub> splits on inspiration. As the diaphragm descends, it causes a further decrease in negative intrathoracic pressure, which increases the flow of blood out of the vena cava into the right side of the heart. This causes flattening of the jugular neck veins. The excess amount of blood in the right side of the heart delays closure of the PV causing P<sub>2</sub> to separate away from A<sub>2</sub> (see schematic). This physiologic split is best heard over the PV area. A<sub>2</sub> and P<sub>2</sub> become a single sound on expiration as intrathoracic pressure becomes less negative. An <b>accentuated A<sub>2</sub></b> is heard in essential hypertension (increased pressure causes it to snap shut), while an <b>accentuated P<sub>2</sub></b> is heard in pulmonary hypertension.<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-010-g001.jpg" id=""></div><a name="PB010009"></a><div class="BB" style="color: rgb(47, 79, 79); ">An <b>S<sub>3</sub> heart sound</b> (see schematic) is the most clinically significant extra heart sound. It is a normal finding in children and young adults, where it reflects a more energetic expansion and filling of the left ventricle. However, it is considered a pathologic finding after 40 years of age. It is thought to be due to a sudden rush of blood entering a volume overloaded left or right ventricle. It is best heard at the apex with the patient in the left lateral decubitus position. It commonly occurs with regurgitant types of murmurs involving any of the valves. It is the first cardiac sign of congestive heart failure, where increased ventricular volume stretches the MV or TV ring causing volume overload from mitral/tricuspid regurgitation. An S<sub>3</sub> heart sound produces a ventricular gallop. An <b>S<sub>4</sub> heart sound</b> (see schematic) coincides with atrial contraction in late diastole and the a wave in the jugular venous pulse (JVP; see below). It is <i>never</i> a normal finding and is due to increased resistance to ventricular filling (decreased compliance) following a vigorous atrial contraction. It is heard best at the apex. Causes of decreased ventricular compliance include concentric ventricular hypertrophy (left/right) and a volume overloaded ventricle (no more room to expand). An S<sub>4</sub> heart sound and the a wave of a JVP are absent in atrial fibrillation. Presence of an S<sub>4</sub> heart sound produces an atrial gallop. Presence of an S<sub>3</sub> and S<sub>4</sub> heart sound is called a summation gallop (see schematic) and sounds like a galloping horse.<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-010-g002.jpg" id=""></div><a name="PB010010"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Heart Murmurs</b></div><a name="PB010011"></a><div class="BB" style="color: rgb(47, 79, 79); ">Heart murmurs may occur in systole and diastole. They may be caused by structural valve disease (e.g., damage due to rheumatic fever) or stretching of the valve ring (e.g., volume overload in left- or right-sided heart failure). Murmurs due to stretching of valve rings are often called functional murmurs. Murmurs often radiate. For example, AV stenosis radiates into the neck and MV regurgitation radiates into the axilla. They are graded 1 to 6 in terms of their intensity. Grade 1 and 2 murmurs are very hard to hear, while grade 3 murmurs are easy to hear. Grade 4 to 6 murmurs are often accompanied by a palpable precordial thrill. Grade 6 murmurs are audible without a stethoscope. Murmurs and abnormal heart sounds (e.g., S<sub>3</sub> and S<sub>4</sub> heart sounds) change their intensity with respirations. Right-sided murmurs and abnormal heart sounds have increased intensity when the patient takes a deep inspiration and holds the breath for 3 to 5 seconds. This is due to the increase in negative intrathoracic pressure drawing blood out of the venous system into the right side of the heart, hence accentuating the murmur and abnormal heart sound. In contradistinction, left-sided heart murmurs and abnormal heart sounds do <i>not</i> change their intensity with deep inspiration. <b>Continuous murmurs</b> occur through systole and diastole. The most common cause of a continuous murmur in children is a cervical venous hum. A patent ductus arteriosus also produces a continuous murmur. <b>Innocent murmurs</b> occur in children from 3 to 7 years old. They are usually grade 2 systolic murmurs that are caused by increased blood flow through the PV. They are best heard in the PV area, and as expected, their intensity increases with deep, held inspiration. <b>Stenosis murmurs</b> occur when there is a problem in opening the valves. Because the AV and PV normally open in systole, AV and PV stenosis occur in systole. They produce an ejection type murmur (schematic A), which has a diamond-shaped configuration. The MV and TV normally open in diastole; hence, the murmurs of MV and TV stenosis are heard in diastole. MV stenosis is accompanied by an opening snap (schematic B), which occurs when the thickened valve is forced open by a forceful atrial contraction. An opening snap is usually absent in TV stenosis. <b>Regurgitant (insufficiency) murmurs</b> occur when there is a problem in closing a valve. Because the MV and TV normally close in systole, these murmurs occur in systole. They are even-intensity pansystolic murmurs (schematic C) that often obliterate the S<sub>1</sub> and S<sub>2</sub> heart sounds. AV and PV regurgitant murmurs occur in diastole immediately after the S<sub>2</sub> heart sound (schematic D).<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-010-g003.jpg" id=""></div><a name="PB010012"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Jugular Venous Pulses (JVPs)</b></div><a name="PB010013"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Normal JVPs</b> (see schematic) have three positive waves (a, c, v) and two negative waves (x, y). The <b>a wave</b> is a positive wave due to atrial contraction in late diastole. It occurs after the P wave in an electrocardiogram. It disappears in atrial fibrillation. A <b>giant a wave</b> occurs when there is restricted filling of the right side of the heart (e.g., TV stenosis, pulmonary hypertension, right ventricular hypertrophy). The <b>c wave</b> is a positive wave due to right ventricular contraction in systole causing bulging of the TV into the right atrium producing increased pressure in the atrium and jugular vein. It correlates with the S<sub>1</sub> heart sound and the upstroke of the carotid pulse. The <b>x wave</b> is a large negative wave occupying most of systole. It is due to downward displacement of the TV when blood is ejected out of the RV into the pulmonary artery. The <b>v wave</b> is a positive wave that correlates with right atrial filling in systole when the TV is closed. The peak of the v wave marks the end of systole and beginning of diastole. A <b>giant c-v wave</b> occurs in TV regurgitation as blood refluxes back into the right atrium during systole. The <b>y wave</b> is a negative wave occupying most of diastole. It is due to opening of the TV with rapid flow of blood into the right ventricle in diastole.<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-010-g004.jpg" id=""></div></html>
<html><a name="HC010011"></a> <br><a name="P010013"></a><div class="PA" style="color: black; "><ol type="1"> <li>Provides oxygen to cardiac muscle</li><ol type="a"> <li>Coronary vessels fill in diastole.
<blockquote style="color: blue; ">Tachycardia: decreases diastole and filling of coronary arteries</blockquote></li><li>Tachycardia (>180 bpm) decreases filling time, leading to ischemia.</li> </ol><li>Left anterior descending (LAD) coronary artery</li><ol type="a"> <li>Distribution</li><ul> <li>(1) Anterior portion of the left ventricle
<blockquote style="color: blue; ">LAD: most common site of coronary artery thrombosis</blockquote></li><li>(2) Anterior two thirds of the interventricular septum</li> </ul><li>Site for 40% to 50% of coronary artery thromboses</li> </ol><li>Right coronary artery (RCA)</li><ol type="a"> <li>Distribution</li><ul> <li>(1) Posteroinferior part of the left ventricle</li><li>(2) Posterior one third of the interventricular septum</li><li>(3) Right ventricle</li><li>(4) Posteromedial papillary muscle in left ventricle</li><li>(5) Primary supply for atrioventricular and sinoatrial nodes</li> </ul><li>Site for 30% to 40% of coronary artery thromboses</li> </ol><li>Left circumflex coronary artery</li><ol type="a"> <li>Supplies the lateral wall of the left ventricle</li><li>Site for 15% to 20% of coronary artery thromboses</li> </ol> </ol>
</div></html>
<html><a name="HC010012"></a> <br><a name="P010014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Ischemic heart disease is the major cause of death in the United States.</li><ol type="a"> <li>It is more common in men.</li><li>Incidence peaks in men after age 60 and in women after age 70.</li> </ol><li>Types of ischemic heart disease</li><ol type="a"> <li>Angina pectoris (most common type)
<blockquote style="color: blue; ">Angina pectoris: most common manifestation of coronary artery disease</blockquote></li><li>Chronic ischemic heart disease</li><li>Sudden cardiac death</li><li>Myocardial infarction</li> </ol><li>Risk factors</li><ol type="a"> <li>Age
<blockquote style="color: blue; ">Angina pectoris: age most important risk factor</blockquote></li><ul> <li>Men ≥ 45 years old, women ≥ 55 years old</li> </ul><li>Family history of premature coronary artery disease or stroke</li><li>Lipid abnormalities</li><ul> <li>(1) Low-density lipoprotein > 160 mg/dL</li><li>(2) High-density lipoprotein (HDL) < 40 mg/dL</li> </ul><li>Smoking tobacco, hypertension, diabetes mellitus</li><li>Subtract 1 from the total number of risk factors if HDL > 60 mg/dL.</li> </ol> </ol>
</div></html>
<html><a name="HC010013"></a> <br><a name="PB010014"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Nonpharmacologic therapy</b> of angina includes losing weight, cessation of smoking, placing the patient on a low cholesterol diet, and encouraging daily aerobic exercise. <b>Pharmacologic therapy</b> for angina involves the use of anti-ischemic agents. Nitrates (release nitric oxide) cause venodilation (reduces preload and wall tension in the ventricles), vasodilation of the coronary arteries, and vasodilation of peripheral resistance arterioles (reduces afterload). β-Blockers decrease myocardial O<sub>2</sub> consumption by reducing heart rate and systolic blood pressure. Calcium channel blockers cause vasodilation of the coronary arteries and peripheral resistance arteries. They are the drug of choice for treating Prinzmetal's angina. Aspirin inhibits platelet aggregation, which decreases the risk for developing a platelet thrombus (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapters 4]]"></span> and <span macro="tag [[14 Hemostasis Disorders]] [[14]]"></span>). Heparin plus aspirin is used for patients with unstable angina and reduces the risk for developing a myocardial infarction and refractory angina. If homocysteine levels are increased, the patient should be placed on pharmacologic doses of folate. If C-reactive protein is increased, the patient should be placed on "statin" drugs to lower the LDL levels to 70 mg/dL or less. This stabilizes disrupted plaques and reduces the risk for thrombosis. Revascularization procedures include percutaneous transluminal coronary angioplasty (PTCA) and stenting. Balloon angioplasty dilates and ruptures the atheromatous plaque to improve blood flow (restenosis commonly occurs) and intracoronary stents (the most common procedure) bypass the obstruction (restenosis less common). Complications are associated with either procedure (e.g., thrombosis, localized dissection). In order to prevent platelet thrombosis in these revascularization procedures, abciximab (inhibits the GpIIb-IIIa fibrinogen receptor in platelets; refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>) is used. Coronary artery bypass graft (CABG) is reserved for patients with left main coronary artery disease and for those patients with symptomatic three-vessel disease. Internal mammary artery grafts have the best graft patency after 10 years, while saphenous vein grafts commonly show "arterialization" of the vessels with fibrosis after 10 years.</div><a name="P010015"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Angina pectoris: males > females</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common in middle-aged males and elderly males</li><li>Females usually affected after menopause</li><li>Within 1 year of a diagnosis of stable angina, 10% to 20% will develop an acute myocardial infarction or unstable angina.</li> </ol><li>Chronic (stable) angina
<blockquote style="color: blue; ">Stable angina: most common type of angina</blockquote></li><ol type="a"> <li>Most common variant</li><li>Causes of stable angina</li><ul> <li>(1) Fixed, atherosclerotic coronary artery disease (most common)</li><ul> <li>(a) One or more vessel obstructions is likely.</li><li>(b) Severity of stenosis is usually >70%.</li> </ul><li>(2) Aortic stenosis or hypertension with concentric LVH</li><ul> <li>O<sub>2</sub> supply is <i>not</i> adequate for the thickened muscle wall.</li> </ul><li>(3) Hypertrophic cardiomyopathy</li><li>(4) Cocaine-induced coronary artery vasoconstriction</li> </ul><li>Pathogenesis</li><ul> <li>Subendocardial ischemia due to decreased coronary artery blood flow or thick muscle wall</li> </ul><li>Clinical findings
<blockquote style="color: blue; ">Stable angina: exercise-induced substernal chest pain</blockquote></li><ul> <li>(1) Exercise-induced substernal chest pain lasting 30 seconds to 30 minutes</li><li>(2) Often accompanied by shortness of breath, diaphoresis, numbness and pain in left arm, shoulder, or jaw
<blockquote style="color: blue; ">Stable angina: subendocardial ischemia with ST-segment depression</blockquote></li><li>(3) Relieved by resting or nitroglycerin</li><li>(4) Stress test shows ST-segment depression > 1 mm (<span>[[Fig. 10-4|Figure 10-4]]</span>).</li> </ul> </ol><li>Prinzmetal's angina</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Intermittent coronary artery vasospasm at rest with or without superimposed coronary artery atherosclerotic disease</li><li>(2) Vasoconstriction is due to platelet thromboxane A<sub>2</sub> or an increase in endothelin.
<blockquote style="color: blue; ">Prinzmetal's angina: vasospasm with transmural ischemia and ST-segment elevation</blockquote></li> </ul><li>Clinical findings</li><ul> <li>Stress test shows ST-segment elevation (transmural ischemia).</li> </ul> </ol><li>Unstable angina
<blockquote style="color: blue; ">Unstable angina: angina at rest; multivessel disease; disrupted plaques</blockquote></li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Severe, fixed, multivessel atherosclerotic disease</li><li>(2) Disrupted plaques with or without platelet nonocclusive thrombi (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapters 4]]"></span> and <span macro="tag [[09 Vascular Disorders]] [[9]]"></span>)</li> </ul><li>Clinical findings</li><ul> <li>(1) Frequent bouts of chest pain at rest or with minimal exertion</li><li>(2) May progress to acute myocardial infarction (MI)</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC010014"></a> <br><a name="P010016"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Prinzmetal's angina: calcium channel blockers vasodilate coronary arteries</blockquote>
<ol type="1"> <li>Progressive CHF resulting from long-term ischemic damage to myocardial tissue
<blockquote style="color: blue; ">Chronic ischemic heart disease: replacement of muscle by fibrous tissue</blockquote></li><li>Replacement of myocardial tissue with noncontractile scar tissue</li><li>Clinical findings</li><ol type="a"> <li>Biventricular CHF</li><li>Angina pectoris</li><li>May develop dilated cardiomyopathy</li> </ol> </ol>
</div></html>
<html><a name="HC010015"></a> <br><a name="P010017"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Sudden cardiac death: unexpected death within 1 hour after symptoms</blockquote>
<ol type="1"> <li>Unexpected death within 1 hour after the onset of symptoms</li><li>Risk factors</li><ol type="a"> <li>Obesity</li><li>Glucose intolerance</li><li>Hypertension</li><li>Recent non-Q wave myocardial infarction</li><li>Smoking</li> </ol><li>Occurs more frequently in the morning hours when hypercoagulability is at its peak</li><li>Pathogenesis</li><ol type="a"> <li>Severe atherosclerotic coronary artery disease
<blockquote style="color: blue; ">Sudden cardiac death: coronary artery thrombosis <i>not</i> usually present</blockquote></li><li>Disrupted fibrous plaques</li><li>Absence of occlusive vessel thrombus (>80% of cases)</li><li>Cause of death is ventricular fibrillation.</li> </ol><li>Diagnosis of exclusion after the following causes are ruled out</li><ol type="a"> <li>Mitral valve prolapse (MVP)
<blockquote style="color: blue; ">MVP sudden death: arrhythmias from mitral regurgitation or CHF</blockquote></li><li>Hypertrophic cardiomyopathy</li><li>Calcific aortic stenosis</li><li>Conduction system abnormalities</li><li>Cocaine abuse</li> </ol> </ol>
</div></html>
<html><a name="HC010016"></a> <br><a name="P010018"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">AMI: most common cause of death in United States</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common cause of death in adults in the United States.</li><li>Prominent in males between 40 and 65 years old</li><li>No predominant sex predilection after 65 years old</li><li>At least 25% of AMIs are clinically unrecognized.</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Sequence</li><ul> <li>(1) Sudden disruption of an atheromatous plaque (see <span>[[Fig. 4-13|Figure 4-13]]</span>)
<blockquote style="color: blue; ">Rupture of disrupted plaque → platelet thrombus → AMI</blockquote></li><li>(2) Subendothelial collagen and thrombogenic necrotic material are exposed.</li><li>(3) Platelets adhere to the exposed material and eventually form an occlusive platelet thrombus.</li> </ul><li>Role of thromboxane A<sub>2</sub> (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>)</li><ul> <li>(1) Contributes to formation of the platelet thrombus</li><li>(2) Causes vasospasm of the artery to reduce blood flow</li> </ul> </ol><li>Less common causes of AMI</li><ol type="a"> <li>Vasculitis (e.g., polyarteritis nodosa, Kawasaki disease)</li><li>Cocaine use
<blockquote style="color: blue; ">Cocaine: AMI with normal coronary arteries</blockquote></li><ul> <li>AMI with normal coronary arteries</li> </ul><li>Embolization of plaque material</li><ul> <li>From atheromatous plaques in the aorta or coronary artery</li> </ul><li>Thrombosis syndromes</li><ul> <li>Examples-antithrombin III deficiency, polycythemia</li> </ul><li>Dissection into the wall of coronary arteries</li><ul> <li>Examples-revascularization procedure, aortic dissection</li> </ul> </ol><li>Types of myocardial infarction
<blockquote style="color: blue; ">AMI: Q wave type transmural, non-Q wave type subendocardial</blockquote></li><ol type="a"> <li>Transmural infarction (Q wave infarction)</li><ul> <li>(1) Involves the full thickness of the myocardium</li><li>(2) New Q waves develop in an electrocardiogram (ECG).</li> </ul><li>Subendocardial infarction (non-Q wave infarction)</li><ul> <li>(1) Involves the inner third of the myocardium</li><li>(2) Q waves are absent.</li> </ul> </ol><li>Reperfusion injury
<blockquote style="color: blue; ">Reperfusion: ↑ short/long-term survival</blockquote></li><ol type="a"> <li>Follows thrombolytic (fibrinolytic) therapy</li><li>Early reperfusion salvages some injured but viable myocytes but destroys myocytes that are irreversibly damaged.</li><ul> <li>(1) Removal of irreversibly damaged myocytes improves short- and long-term function and survival.</li><li>(2) Prevents any further damage to myocardial cells</li><li>(3) Limits the size of the infarction</li> </ul><li>Reperfusion histologically alters irreversibly damaged cells.</li><ul> <li>(1) Produces contraction band necrosis
<blockquote style="color: blue; ">Contraction band necrosis: reperfusion; hypercontraction myofibrils due to Ca<sup>2+</sup></blockquote></li><li>(2) Caused by hypercontraction of myofibrils in dying cells</li><ul> <li>Due to the influx of Ca<sup>2+</sup> into the cytosol</li> </ul> </ul> </ol><li>Gross and microscopic findings of AMI</li><ol type="a"> <li>During 0 to 24 hours</li><ul> <li>(1) No gross changes are evident until 24 hours.</li><li>(2) Coagulation necrosis is present within 12 to 24 hours.</li><li>(3) Neutrophils begin to enter the area of infarction from the periphery.</li> </ul><li>During 1 to 3 days</li><ul> <li>(1) Pallor of the infarcted tissue</li><li>(2) Myocyte nuclei and striations disappear (see <span>[[Fig. 1-11A|Figure 1-11]]</span>).</li><li>(3) Neutrophils are abundant and lyse dead myocardial cells.
<blockquote style="color: blue; ">AMI: coagulation necrosis within 24 hours</blockquote></li> </ul><li>During 3 to 7 days</li><ul> <li>(1) Red granulation tissue surrounds the area of infarction.
<blockquote style="color: blue; ">AMI: heart softest 3-7 days; danger of rupture</blockquote></li><li>(2) Macrophages begin to remove necrotic debris.</li> </ul><li>During 7 to 10 days</li><ul> <li>(1) The necrotic area is bright yellow (<span>[[Fig. 10-5|Figure 10-5]]</span>; see also <span>[[Fig. 1-11B|Figure 1-11]]</span>).</li><li>(2) Granulation tissue and collagen formation are well developed.</li> </ul><li>During 2 months</li><ul> <li>Infarcted tissue replaced by white, patchy, noncontractile scar tissue</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Sudden onset of severe, crushing retrosternal pain
<blockquote style="color: blue; ">AMI: retrosternal pain, radiation to left arm/shoulder, diaphoresis</blockquote></li><ul> <li>(1) Lasts >30 minutes</li><li>(2) <i>Not</i> relieved by nitroglycerin</li><li>(3) Usually radiates down the left arm into the shoulders or into the jaw or epigastrium</li><li>(4) Associated with sweating (diaphoresis), anxiety, and hypotension</li> </ul><li>"Silent" AMIs in ∼20% of cases</li><ul> <li>(1) May occur in the elderly and in individuals with diabetes mellitus</li><li>(2) Due to high pain threshold or problems with nervous system</li> </ul><li>Q wave AMI has increased early mortality rate compared to non-Q wave AMI.
<blockquote style="color: blue; ">Q wave AMI: ↑ early mortality rate</blockquote></li><li>Non-Q wave AMI</li><ul> <li>(1) Increased risk of reinfarction</li><li>(2) Increased risk for sudden cardiac death post-MI
<blockquote style="color: blue; ">Non-Q wave AMI: ↑ risk for SCD</blockquote></li> </ul> </ol><li>Complications</li><ol type="a"> <li>Cardiogenic shock occurs in ∼7% of cases.</li><ul> <li>Revascularization improves survival.</li> </ul><li>Arrhythmias</li><ul> <li>(1) Ventricular premature contractions (most common)
<blockquote style="color: blue; ">Ventricular fibrillation: most common cause of death in acute MI</blockquote></li><li>(2) Most common cause of death is ventricular fibrillation.</li><ul> <li>Frequently associated with cardiogenic shock</li> </ul><li>(3) Heart block</li><ul> <li>(a) Occurs in 5% of inferior AMIs</li><li>(b) Occurs in 3% of anterior AMIs</li> </ul> </ul><li>Congestive heart failure</li><ul> <li>Usually occurs within the first 24 hours</li> </ul><li>Rupture
<blockquote style="color: blue; ">Myocardial rupture: most common at 3-7 days</blockquote></li><ul> <li>(1) Most commonly occurs between days 3 and 7 (range, 1-10 days)</li><li>(2) Anterior wall rupture (<span>[[Fig. 10-6|Figure 10-6]]</span>)</li><ul> <li>(a) Causes cardiac tamponade</li><li>(b) Associated with thrombosis of the LAD coronary artery</li> </ul><li>(3) Posteromedial papillary muscle rupture or dysfunction
<blockquote style="color: blue; ">Posteromedial papillary muscle rupture: RCA thrombosis; mitral regurgitation</blockquote></li><ul> <li>(a) Most often associated with RCA thrombosis</li><ul> <li>Most often with inferior AMIs</li> </ul><li>(b) Acute onset of mitral valve regurgitation and LHF</li> </ul><li>(4) Interventricular septum rupture</li><ul> <li>(a) Most often associated with LAD coronary artery thrombosis</li><li>(b) Produces a left-to-right shunt causing RHF</li><ul> <li>Increased O<sub>2</sub> saturation and pressure in right ventricle</li> </ul> </ul> </ul><li>Mural thrombus
<blockquote style="color: blue; ">Mural thrombus: danger of embolization</blockquote></li><ul> <li>(1) Occurs in ∼10% of AMIs</li><li>(2) Most often associated with LAD coronary artery thrombosis</li><li>(3) Danger of embolization</li> </ul><li>Fibrinous pericarditis with or without effusion (see <span>[[Fig. 2-7|Figure 2-7]]</span>)</li><ul> <li>(1) Days 1 to 7 of a Q wave AMI</li><ul> <li>(a) Substernal chest pain is relieved by leaning forward and aggravated by leaning backward.</li><li>(b) A precordial friction rub is present (see later).</li><ul> <li>Due to increased vessel permeability in the pericardium; exudate of acute inflammation
<blockquote style="color: blue; ">Fibrinous pericarditis: early (acute inflammation) and late complication (autoimmune)</blockquote></li> </ul> </ul><li>(2) Autoimmune pericarditis</li><ul> <li>(a) Develops 6 to 8 weeks after an acute MI</li><li>(b) Autoantibodies are directed against damaged pericardial antigens.</li><li>(c) Fever and a precordial friction rub are present.</li> </ul> </ul><li>Ventricular aneurysm (<span>[[Fig. 10-7|Figure 10-7]]</span>)</li><ul> <li>(1) Clinically recognized within 4 to 8 weeks</li><ul> <li>Begins developing in the first 48 hours.</li> </ul><li>(2) Precordial bulge occurs during systole.</li><ul> <li>Blood enters the aneurysm causing anterior chest wall movement.</li> </ul><li>(3) Complications
<blockquote style="color: blue; ">Ventricular aneurysm: CHF most common cause of death</blockquote></li><ul> <li>(a) CHF occurs due to the lack of contractile tissue.</li><li>(b) Danger of embolization of clot material</li><li>(c) Rupture is uncommon.</li><ul> <li>Scar tissue has good tensile strength.</li> </ul> </ul> </ul><li>Right ventricular AMI</li><ul> <li>(1) Associated with RCA thrombosis</li><li>(2) Occurs in one third of inferior AMIs</li><ul> <li>Clinically significant in 30% of cases</li> </ul><li>(3) Clinical findings
<blockquote style="color: blue; ">RV AMI: hypotension, RHF, preserved LV function</blockquote></li><ul> <li>Hypotension, RHF, and preserved left ventricle function</li> </ul> </ul> </ol><li>Laboratory diagnosis of AMI (<span>[[Fig. 10-8|Figure 10-8]]</span>)</li><ol type="a"> <li>Serial testing for creatine kinase isoenzyme MB (CK-MB)</li><ul> <li>(1) CK-MB appears within 4 to 8 hours; peaks at 24 hours; disappears within 1.5 to 3 days.</li><ul> <li>Sensitivity and specificity 95%.</li> </ul><li>(2) Reinfarction
<blockquote style="color: blue; ">Reinfarction: reappearance of CK-MB after 3 days</blockquote></li><ul> <li>(a) Occurs in 10% of AMIs</li><li>(b) Reappearance of CK-MB after 3 days</li> </ul> </ul><li>Serial testing for cardiac troponins I (cTnI) and T (cTnT)
<blockquote style="color: blue; ">cTnI, cTnT: cannot diagnose reinfarction</blockquote></li><ul> <li>(1) Normally regulate calcium-mediated contraction</li><li>(2) cTnI and cTnT appear within 3 to 12 hours; peak at 24 hours; disappear within 7 to 10 days.</li><ul> <li>(a) Sensitivity 84% to 96%, specificity 80% to 95%</li><li>(b) False positive results are usually related to ischemia (e.g., unstable angina).
<blockquote style="color: blue; ">cTnI, cTnT: gold standard for diagnosis of AMI</blockquote></li> </ul><li>(3) CK-MB is used in conjunction with troponins to diagnose an AMI.</li><ul> <li>(a) Detects reinfarction (troponins cannot)</li><li>(b) Improves overall sensitivity and specificity in diagnosing an AMI</li> </ul> </ul><li>Lactate dehydrogenase (LDH)<sub>1-2</sub> "flip"</li><ul> <li>(1) Normally, LDH<sub>2</sub> is higher than LDH<sub>1</sub>.</li><ul> <li>In AMI, LDH<sub>1</sub> in cardiac muscle is released, causing the "flip."</li> </ul><li>(2) LDH<sub>1-2</sub></li><ul> <li>Appears within 10 hours; peaks at 2 to 3 days; disappears within 7 days</li> </ul><li>(3) This test has been replaced by troponins I and T.</li> </ul> </ol><li>Correlation of ECG changes with microscopic changes (<span>[[Fig. 10-9|Figure 10-9]]</span>)
<blockquote style="color: blue; ">ECG findings in AMI: inverted T waves, elevated ST segment, Q waves</blockquote></li><ol type="a"> <li>Inverted T waves</li><ul> <li>Correlate with areas of ischemia at the periphery of the infarct</li> </ul><li>Elevated ST segment</li><ul> <li>Correlates with injured myocardial cells surrounding the area of necrosis</li> </ul><li>New Q waves</li><ul> <li>Correlate with the area of coagulation necrosis</li> </ul> </ol><li>Classic ECG patterns in AMI</li><ol type="a"> <li>LAD coronary artery anterior wall infarction</li><ul> <li>Q waves in leads V<sub>1</sub>-V<sub>4</sub></li> </ul><li>Anteroseptal infarction due to proximal LAD occlusion</li><ul> <li>Q waves in leads V<sub>1</sub>-V<sub>2</sub></li> </ul><li>Anterolateral infarction due to mid-LAD or circumflex coronary arteries</li><ul> <li>Q waves in leads V<sub>4</sub>-V<sub>6</sub>, I, aVL</li> </ul><li>Lateral wall infarction due to left circumflex artery</li><ul> <li>Q waves in leads I, aVL</li> </ul><li>RCA inferior wall infarction</li><ul> <li>Q waves in leads II, III, aVF</li> </ul><li>Posterior wall infarction due to posterior descending artery occlusion</li><ul> <li>(1) Q wave in lead V<sub>6</sub></li><li>(2) R wave > S wave in lead V<sub>1</sub></li> </ul> </ol> </ol>
</div><a name="PB010015"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Nonpharmacologic therapy</b> of an acute MI includes limiting patient activity, cessation of smoking, low salt diet, and placing the patient on a low cholesterol diet. <b>Pharmacologic therapy</b> includes anti-platelet therapy (aspirin, clopidogrel if allergic to aspirin); nitrates (reduce coronary artery spasm; venodilation decreases ventricular preload, hence reducing myocardial O<sub>2</sub> consumption); pain medication (morphine); nasal O<sub>2</sub> (2-4 liters/minute); β-blockers (decrease sympathetic tone, hence decreasing myocardial O<sub>2</sub> consumption; also prevent tachyarrhythmias); ACE inhibitors (reduce left ventricular dysfunction and dilation, hence slowing the progression of congestive heart failure); warfarin (often used along with aspirin); and myocardial reperfusion, which markedly improves survival. Reperfusion can be accomplished using fibrinolytic therapy (if duration of pain is <6 hours); percutaneous coronary intervention; or CABG. It is important to measure the ejection fraction prior to discharge to evaluate the severity of damage and to provide an index of prognosis.</div></html>
![[10.IV.A.Coronary artery blood flow]]
<<tiddler [[10.IV.A.Coronary artery blood flow]]>>
![[10.IV.B.Epidemiology]]
<<tiddler [[10.IV.B.Epidemiology]]>>
![[10.IV.C.Angina pectoris]]
<<tiddler [[10.IV.C.Angina pectoris]]>>
![[10.IV.D.Chronic ischemic heart disease]]
<<tiddler [[10.IV.D.Chronic ischemic heart disease]]>>
![[10.IV.E.Sudden cardiac death (SCD)]]
<<tiddler [[10.IV.E.Sudden cardiac death (SCD)]]>>
![[10.IV.F.Acute myocardial infarction (AMI)]]
<<tiddler [[10.IV.F.Acute myocardial infarction (AMI)]]>>
<html><a name="HC010045"></a> <br><a name="P010067"></a><div class="PA" style="color: black; "><ol type="1"> <li>Metastasis is more common than primary tumors.
<blockquote style="color: blue; ">Heart tumors: metastasis > primary tumors</blockquote></li><ul> <li>Example-extension of a primary lung cancer</li> </ul><li>Pericardium is the most common site for metastasis.</li><ul> <li>Leads to pericarditis and effusions</li> </ul><li>Primary tumors or tumor-like conditions:</li><ul> <li>Cardiac myxoma, rhabdomyoma</li> </ul> </ol>
</div></html>
<html><a name="HC010046"></a> <br><a name="P010068"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common primary adult tumor</li><li>Pathology</li><ol type="a"> <li>Benign primary mesenchymal tumor
<blockquote style="color: blue; ">Cardiac myxoma: most common in left atrium</blockquote></li><li>Approximately 90% arise from the left atrium (<span>[[Fig. 10-28|Figure 10-28]]</span>)</li><li>Sessile or pedunculated</li><li>"Ball-valve" effect blocks the mitral valve orifice</li><ul> <li>Blocks diastolic filling of the ventricle, simulating mitral valve stenosis</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Nonspecific findings</li><ul> <li>Fever, fatigue, malaise, anemia</li> </ul><li>Complications</li><ul> <li>Embolization, syncopal episodes (blocks mitral valve orifice)</li> </ul> </ol><li>Diagnosis</li><ol type="a"> <li>Transesophageal ultrasound</li><li>Most useful study for viewing the left atrium</li><ul> <li>The left atrium is the most posteriorly located chamber.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC010047"></a> <br><a name="P010069"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common primary tumor of the heart in infants and children
<blockquote style="color: blue; ">Myxomas occur in adults; rhabdomyomas occur in children.</blockquote></li><ul> <li>Major association with tuberous sclerosis (refer to <span macro="tag [[25 Nervous System and Special Sensory Disorders]] [[Chapter 25]]"></span>)</li> </ul><li>Hamartoma (non-neoplastic) arising from cardiac muscle</li> </ol>
</div></html>
![[10.IX.A.Epidemiology]]
<<tiddler [[10.IX.A.Epidemiology]]>>
![[10.IX.B.Cardiac myxoma]]
<<tiddler [[10.IX.B.Cardiac myxoma]]>>
![[10.IX.C.Rhabdomyoma]]
<<tiddler [[10.IX.C.Rhabdomyoma]]>>
<html><a name="HC010018"></a><span>[[Fig. 10-10|Figure 10-10]]</span> <br> <br><a name="P010025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Chorionic villus in the placenta (refer to <span macro="tag [[21 Female Reproductive Disorders and Breast Disorders]] [[Chapter 21]]"></span>)</li><ol type="a"> <li>Derived from the fetus</li><li>Primary site for O<sub>2</sub> exchange</li><li>Chorionic villus vessels become the umbilical vein.
<blockquote style="color: blue; ">Chorionic villus: primary site for O<sub>2</sub> exchange</blockquote></li> </ol><li>Umbilical vein
<blockquote style="color: blue; ">Umbilical vein: highest P<span style="font-variant:small-caps;">o</span><sub>2</sub> in fetal circulation</blockquote></li><ul> <li>Vessel with the highest P<span style="font-variant:small-caps;">o</span><sub>2</sub> in the fetal circulation</li> </ul><li>Inferior vena cava blood drains into the right atrium.</li><ul> <li>Most blood is directly shunted into the left atrium through the foramen ovale.</li> </ul><li>Superior vena cava blood</li><ul> <li>Most blood is directed from the right atrium into the right ventricle.</li> </ul><li>Pulmonary artery blood</li><ol type="a"> <li>Blood is shunted through a patent ductus arteriosus into the aorta.</li><ul> <li>Ductus arteriosus is kept open by prostaglandin E<sub>2</sub>, a vasodilator synthesized by the placenta.</li> </ul><li>Fetal pulmonary arteries
<blockquote style="color: blue; ">Fetal circulation: foramen ovale and ductus arteriosus are patent</blockquote></li><ul> <li>(1) Hypertrophied from chronic vasoconstriction due to decreased P<span style="font-variant:small-caps;">o</span><sub>2</sub></li><li>(2) Prevents blood from entering the pulmonary capillaries and left atrium</li> </ul> </ol><li>Descending aorta</li><ol type="a"> <li>Blood flows toward the placenta via two umbilical arteries.</li><ul> <li>Increased risk for congenital abnormalities with single umbilical artery
<blockquote style="color: blue; ">Single umbilical artery: ↑ risk congenital abnormalities</blockquote></li> </ul><li>Umbilical arteries have the lowest O<sub>2</sub> concentration.</li> </ol><li>Changes at birth</li><ol type="a"> <li>Ductus arteriosus (DA) closes
<blockquote style="color: blue; ">DA: becomes ligamentum arteriosum</blockquote></li><ul> <li>(1) Anatomic closure within 2 to 8 weeks in most cases</li><li>(2) Becomes the ligamentum arteriosum</li> </ul><li>Gas exchange occurs in the lungs.</li><ul> <li>Pulmonary artery opens up due to the increase in Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>.</li> </ul><li>Foramen ovale functionally closes in 24 hours.
<blockquote style="color: blue; ">Newborn: foramen ovale and ductus arteriosus are closed</blockquote></li> </ol> </ol>
</div></html>
<html><a name="HC010019"></a> <br><a name="P010026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common heart disease in children</li><li>Incidence is higher in premature than full-term newborns.</li><li>No identifiable cause for CHD in ∼90% of cases.
<blockquote style="color: blue; ">CHD: ↑ risk with ↑ maternal age</blockquote></li><li>Risk factors for CHD</li><ul> <li>(1) Previous child with CHD (1:50 chance second child with CHD)</li><li>(2) Down syndrome and other trisomy syndromes (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><li>(3) Maternal risk factors</li><ul> <li>(a) Increased age</li><li>(b) Poorly controlled diabetes mellitus</li><li>(c) Alcohol intake</li><li>(d) Congenital infection (e.g., rubella; refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li> </ul> </ul><li>Spectrum of CHD</li><ul> <li>(1) Valvular diseases (e.g., pulmonary stenosis)</li><li>(2) Shunts (noncyanotic and cyanotic)</li> </ul><li>Systemic complications</li><ul> <li>(1) Secondary polycythemia with clubbing of the fingers in cyanotic CHD</li><ul> <li>Decreased Pa<span style="font-variant:small-caps;">o</span><sub>2</sub> stimulates the release of erythropoietin.</li> </ul><li>(2) Increased risk for developing infective endocarditis</li><li>(3) Metastatic abscesses (particularly in cyanotic CHD)</li> </ul> </ol><li>O<sub>2</sub> saturation (Sa<span style="font-variant:small-caps;">o</span><sub>2</sub>) in shunts
<blockquote style="color: blue; ">CHD shunts: left-to-right; right-to-left (often cyanotic)</blockquote></li><ol type="a"> <li>Left-sided to right-sided heart shunts
<blockquote style="color: blue; ">Left-to-right shunts: danger of shunt reversal if uncorrected</blockquote></li><ul> <li>There is an increased Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> (step up) from 75% to ∼80% in affected chambers and vessels.</li> </ul><li>Right-sided to left-sided heart shunts</li><ul> <li>(1) Decreased Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> (step down) from 95% to ∼80% in affected chambers and vessels</li><li>(2) Cyanosis depends on how low Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> percentage is in the left side of the heart.</li> </ul> </ol><li>Left-sided to right-sided heart shunts</li><ol type="a"> <li>Volume overload occurs in the right side of the heart; may have several complications:</li><ul> <li>(1) Pulmonary hypertension (PH)</li><li>(2) RVH due to PH</li><ul> <li>PH increases afterload the right ventricle must contract against to eject blood.</li> </ul><li>(3) LVH due to excess blood originating from the right side of the heart</li><ul> <li>Eccentric hypertrophy due to volume overload (see section II)</li> </ul><li>(4) Reversal of the shunt</li><ul> <li>(a) Occurs when pressure in the right ventricle overrides the left ventricular pressure</li><li>(b) Cyanosis (Eisenmenger syndrome) and clubbing develop (<span>[[Fig. 10-11|Figure 10-11]]</span>).</li><ul> <li>Another term is cyanosis tardive (late-onset cyanosis).</li> </ul> </ul> </ul><li>Ventricular septal defect (VSD; <span>[[Fig. 10-12A|Figure 10-12]]</span>)
<blockquote style="color: blue; ">VSD: most common congenital heart disease in children</blockquote></li><ul> <li>(1) Most common CHD (20% of cases)</li><li>(2) Defect in the membranous interventricular septum</li><li>(3) Harsh pansystolic murmur at lower left sternal border
<blockquote style="color: blue; ">VSD: defect in membranous septum</blockquote></li><li>(4) Associations</li><ul> <li>(a) Corrected transposition</li><li>(b) Tetralogy of Fallot</li><li>(c) Cri du chat syndrome (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><li>(d) Fetal alcohol syndrome (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li> </ul><li>(5) Increased Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> in right ventricle and pulmonary artery</li><li>(6) Spontaneously close in 30% to 50% of cases</li><li>(7) Lifetime risk for infective endocarditis ranges from 5% to 30%.</li> </ul><li>Atrial septal defect (ASD; <span>[[Fig. 10-12B|Figure 10-12]]</span>)
<blockquote style="color: blue; ">ASD: most common CHD in adults</blockquote></li><ul> <li>(1) Patent foramen ovale (secundum type; most common type)</li><ul> <li>(a) Accounts for 10% to 15% of all CHD
<blockquote style="color: blue; ">ASD: patent foramen ovale</blockquote></li><li>(b) Most common adult CHD</li> </ul><li>(2) Associations</li><ul> <li>(a) Fetal alcohol syndrome</li><li>(b) Down syndrome (primum type in 25%)</li><li>(c) Paradoxic embolism (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li> </ul><li>(3) Mild systolic murmur at upper sternal border in secundum type</li><li>(4) Fixed splitting of S<sub>2</sub>
<blockquote style="color: blue; ">ASD: fixed splitting of S<sub>2</sub> ; most common adult CHD</blockquote></li><ul> <li>Excess blood in right atrium causes delay in closure of pulmonary valve.</li> </ul><li>(5) Increased Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> in right atrium, right ventricle and pulmonary artery</li> </ul><li>Patent ductus arteriosus (PDA; <span>[[Fig. 10-12C|Figure 10-12]]</span>)</li><ul> <li>(1) Accounts for 10% of all CHD</li><li>(2) Ductus arteriosus remains open.</li><ul> <li>Isolated defect in 75% of cases</li> </ul><li>(3) Associations</li><ul> <li>(a) Congenital rubella</li><li>(b) Respiratory distress syndrome</li><ul> <li>Due to decreased Pa<span style="font-variant:small-caps;">o</span><sub>2</sub></li> </ul><li>(c) Complete transposition</li> </ul><li>(4) Increased Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> in the pulmonary artery</li><li>(5) Reversal of the shunt due to pulmonary hypertension</li><ul> <li>(a) Unoxygenated blood enters the aorta <i>below</i> the subclavian artery</li><li>(b) Produces a pink upper body and cyanotic lower body
<blockquote style="color: blue; ">PDA: closed with indomethacin; machinery murmur</blockquote></li> </ul><ul> <li>Called differential cyanosis</li> </ul><li>(6) Machinery murmur is heard during systole and diastole.</li><li>(7) Treatment</li><ul> <li>(a) Intravenous indomethacin inhibits prostaglandin E<sub>2</sub> (vasodilator)</li><li>(b) Surgical closure (e.g., banding)</li> </ul> </ul> </ol><li>Right-sided to left-sided heart shunts</li><ol type="a"> <li>Cyanotic CHD</li><li>Complications (see above)</li><li>Tetralogy of Fallot</li><ul> <li>(1) Most common cyanotic CHD (<span>[[Fig. 10-12D|Figure 10-12]]</span>)
<blockquote style="color: blue; ">Tetralogy of Fallot: most common cyanotic CHD</blockquote></li><ul> <li>(a) Accounts for 10% of all cases of CHD</li><li>(b) Accounts for 50% to 70% of cyanotic CHD</li><li>(c) Accounts for 85% of adults with cyanotic CHD</li> </ul><li>(2) Defects</li><ul> <li>(a) Ventricular septal defect</li><li>(b) Infundibular or valvular pulmonary stenosis</li><li>(c) Right ventricular hypertrophy</li><li>(d) Dextrorotated aorta with right-sided aortic arch (25% of cases)</li> </ul><li>(3) Onset of cyanosis usually after 3 months of age</li><li>(4) Systolic murmur is heard along the left sternal border.</li><li>(5) Minimal pulmonary valve (PV) stenosis
<blockquote style="color: blue; ">Tetralogy of Fallot: degree of PV stenosis correlates with presence or absence of cyanosis</blockquote></li><ul> <li>(a) Leads to increased oxygenation of blood in the lungs</li><li>(b) Less right-to-left shunting through the VSD</li><li>(c) Absence of cyanosis (Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> > 80%)</li> </ul><li>(6) Severe PV stenosis</li><ul> <li>(a) Less oxygenation of blood in the lungs</li><li>(b) Increased right-to-left shunting through the VSD</li><li>(c) Cyanosis (Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> < 80%)</li> </ul><li>(7) Decreased Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> in the left ventricle and aorta</li><li>(8) Cardioprotective shunts increase oxygenation.
<blockquote style="color: blue; ">Cardioprotective shunts: ASD, PDA</blockquote></li><ul> <li>(a) ASD steps up Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> in the right atrium.</li><li>(b) PDA shunts blood from the aorta to the pulmonary artery.</li> </ul><li>(9) Tet spells (hypoxic spells)
<blockquote style="color: blue; ">Tet spells: squatting ↑ systemic vascular resistance; ↑ Pa<span style="font-variant:small-caps;">o</span><sub>2</sub></blockquote></li><ul> <li>(a) Caused by a sudden increase in hypoxemia and cyanosis</li><li>(b) Squatting increases systemic vascular resistance, causing temporary reversal of the shunt.</li><li>(c) Unoxygenated blood is forced back into the pulmonary artery for oxygenation.</li> </ul> </ul><li>Complete transposition of the great vessels (<span>[[Fig. 10-12E|Figure 10-12]]</span>)</li><ul> <li>(1) Defects</li><ul> <li>(a) Aorta arises from the right ventricle.</li><li>(b) Pulmonary artery arises from the left ventricle.</li><li>(c) Left and right atria are normal.</li> </ul><li>(2) Cardioprotective shunts
<blockquote style="color: blue; ">Transposition: aorta empties RV, pulmonary artery empties LV, atria normal</blockquote></li><ul> <li>(a) ASD steps up Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> in the right atrium.</li><ul> <li>Increases Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> in the right ventricle for delivery to tissue via the aorta</li> </ul><li>(b) VSD shunts blood into the left ventricle for oxygenation in the lungs via the pulmonary artery.</li><li>(c) PDA shunts blood into the pulmonary artery for oxygenation in the lungs.</li> </ul> </ul><li>Other types of cyanotic CHD</li><ul> <li>(1) Total anomalous pulmonary venous return</li><ul> <li>Pulmonary vein empties oxygenated blood into the right atrium.</li> </ul><li>(2) Truncus arteriosus</li><ul> <li>Aorta and pulmonary artery share a common trunk and intermix blood.</li> </ul><li>(3) Tricuspid atresia</li><ul> <li>Usually have an ASD with a right-to-left shunt</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC010020"></a><span>[[Fig. 10-12F|Figure 10-12]]</span> <br> <br><a name="P010027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Accounts for 10% of all CHD</li><li>Infantile (preductal) coarctation</li><ol type="a"> <li>Accounts for 70% of coarctations
<blockquote style="color: blue; ">Infantile coarctation: associated with Turner's syndrome</blockquote></li><li>Constriction of aorta between the subclavian artery and ductus arteriosus</li><li>Associated with Turner's syndrome</li> </ol><li>Adult coarctation</li><ol type="a"> <li>Accounts for 30% of coarctations</li><li>Develops during adult life</li><li>Constriction of the aorta distal to the ligamentum arteriosum</li><ul> <li>(1) Blood flow into the proximally located branch vessels is increased.</li><li>(2) Blood flow below the constriction is decreased.</li><li>(3) Produces a systolic murmur</li><li>(4) Additional defect is a bicuspid aortic valve (50% of cases)</li> </ul><li>Clinical findings proximal to the constriction
<blockquote style="color: blue; ">Adult coarctation: disparity between upper/lower extremity blood pressure > 10 mm Hg</blockquote></li><ul> <li>(1) Increased upper extremity blood pressure</li><li>(2) Dilation of aorta and aortic valve ring (regurgitation)</li><ul> <li>Increased risk for developing an aortic dissection</li> </ul><li>(3) Increased cerebral blood flow (increased risk for berry aneurysms)</li> </ul><li>Clinical findings distal to the constriction</li><ul> <li>(1) Decreased blood pressure in the lower extremity</li><li>(2) Leg claudication (pain in calf or buttocks when walking)</li><li>(3) Decreased renal blood flow
<blockquote style="color: blue; ">Hypertension: due to activation RAA system</blockquote></li><ul> <li>Activates the renin-angiotensin-aldosterone (RAA) system, causing hypertension</li> </ul> </ul><li>Development of collateral circulation</li><ul> <li>(1) Collaterals develop between intercostal arteries above and below the constriction.</li><ul> <li>(a) Anterior intercostal arteries (AIAs) arise from internal thoracic artery.</li><li>(b) Posterior intercostal arteries (PIAs) arise from aorta.</li><li>(c) Increased pressure in the aorta extends into the subclavian artery → into the internal thoracic artery → into the AIAs, which stimulates the formation of a collateral circulation with the PIAs causing reversal of the blood flow into the aorta.
<blockquote style="color: blue; ">Coarctation collaterals: AIA-PIA to aorta; SEA-IEA to external iliac artery</blockquote></li> </ul><li>(2) Collateral circulation between the superior epigastric artery (SEA) and the inferior epigastric artery (IEA)</li><ul> <li>(a) Internal thoracic artery becomes the SEA.</li><li>(b) SEA forms collaterals with the IEA (branch of the external iliac artery).</li><li>(c) Reversal of flood flow in the IEA forces blood into the external iliac artery.</li> </ul><li>(3) Chest radiograph shows rib notching on the undersurface of the ribs.</li><ul> <li>Increased blood flow through enlarged, pulsating intercostal arteries wears the bone away.</li> </ul> </ul><li>Surgical removal of a coarctation corrects the hypertension.</li> </ol> </ol>
</div></html>
![[10.V.A.Fetal circulation (Fig. 10-10)]]
<<tiddler [[10.V.A.Fetal circulation (Fig. 10-10)]]>>
![[10.V.B.Features of congenital heart disease]]
<<tiddler [[10.V.B.Features of congenital heart disease]]>>
![[10.V.C.Coarctation of the aorta (Fig. 10-12F)]]
<<tiddler [[10.V.C.Coarctation of the aorta (Fig. 10-12F)]]>>
<html><a name="HC010022"></a> <br><a name="P010031"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Occurs at 5 to 15 years of age</li><li>Develops over 1 to 5 weeks (average 20 days) after group A streptococcal (<i>Streptococcus pyogenes</i>) pharyngitis
<blockquote style="color: blue; ">Acute RF: after group A streptococcal pharyngitis</blockquote></li><ul> <li>Only site for infection leading to RF</li> </ul><li>Risk factors for streptococcal pharyngitis</li><ul> <li>(1) Crowding</li><li>(2) Poverty</li><li>(3) Young age</li> </ul><li>Recurrent RF produces chronic valvular disease.</li> </ol><li>Pathogenesis
<blockquote style="color: blue; ">Acute RF: immune-mediated type II hypersensitivity reaction; cell-mediated immunity type IV</blockquote></li><ol type="a"> <li>Immune-mediated disease that follows group A streptococcal infection</li><li>Antibodies develop against group A streptococcal M proteins.</li><ul> <li>(1) Antibodies cross-react with similar proteins in human tissue (called mimicry).</li><ul> <li>Type II hypersensitivity reaction</li> </ul><li>(2) Cell-mediated immunity has also been implicated.</li><ul> <li>Type IV hypersensitivity reaction</li> </ul> </ul><li>Nephrogenic strains of group A streptococcus lack M protein.</li><ul> <li>Never associated with RF</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Migratory polyarthritis (∼75%)
<blockquote style="color: blue; ">Acute RF: migratory polyarthritis most common initial presentation</blockquote></li><ul> <li>(1) Most common initial presentation of acute rheumatic fever</li><li>(2) Occurs in large joints (knees), ankles, and wrists</li><li>(3) <i>No</i> permanent joint damage</li> </ul><li>Carditis (∼35%)</li><ul> <li>(1) Most serious complication</li><li>(2) Fibrinous pericarditis</li><ul> <li>Precordial chest pain with friction rub</li> </ul><li>(3) Myocarditis</li><ul> <li>(a) Most common cause of death in acute disease
<blockquote style="color: blue; ">Acute RF: myocarditis most common cause of death</blockquote></li><li>(b) Aschoff bodies are present.</li><ul> <li>Central area of fibrinoid necrosis surrounded by Anitschkow cells (reactive histiocytes)</li> </ul> </ul><li>(4) Endocarditis</li><ul> <li>(a) Most commonly involves the MV (then aortic valve)
<blockquote style="color: blue; ">Acute RF: MV most often involved followed by AV</blockquote></li><li>(b) Sterile, verrucoid-appearing vegetations develop along the line of closure of the valve (<span>[[Fig. 10-13|Figure 10-13]]</span>).</li><ul> <li>Embolism is uncommon.</li> </ul><li>(c) MV regurgitation or aortic valve (AV) regurgitation</li><ul> <li>May result in congestive heart failure</li> </ul><li>(d) Recurrent infection of the MV and AV leads to MV stenosis or AV stenosis.
<blockquote style="color: blue; ">Rheumatic fever: mitral regurgitation in acute attack; mitral stenosis in chronic disease</blockquote></li> </ul> </ul><li>Subcutaneous nodules (∼10%) occur on extensor surfaces.</li><li>Erythema marginatum (∼10%)</li><ul> <li>Evanescent circular ring of erythema that develops around normal skin</li> </ul><li>Sydenham's chorea (∼10%)</li><ul> <li>(1) Reversible rapid, involuntary movements affecting all muscles</li><li>(2) Late manifestation of acute RF</li> </ul> </ol><li>Diagnosis of acute RF (revised Jones criteria)
<blockquote style="color: blue; ">Acute RF: diagnose with Jones criteria</blockquote></li><ol type="a"> <li>One major and two minor criteria if supported by evidence of an antecedent group A streptococcal pharyngitis</li><li>Major criteria
<blockquote style="color: blue; ">Acute RF: carditis, arthritis, chorea, erythema marginatum subcutaneous nodules</blockquote></li><ul> <li>(1) Carditis</li><li>(2) Migratory polyarthritis</li><li>(3) Chorea</li><li>(4) Erythema marginatum</li><li>(5) Subcutaneous nodules</li> </ul><li>Minor criteria</li><ul> <li>(1) Previous RF or rheumatic heart disease</li><li>(2) Arthralgia (pain without joint swelling)</li><li>(3) Fever</li><li>(4) Increased acute phase reactants (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>)</li><ul> <li>(a) Increased erythrocyte sedimentation rate (ESR; refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>)</li><li>(b) Increased C-reactive protein</li><li>(c) Absolute neutrophilic leukocytosis</li> </ul><li>(5) Prolonged PR interval (first-degree heart block)</li> </ul><li>Laboratory tests
<blockquote style="color: blue; ">Acute RF: ↑ASO and DNase B titers</blockquote></li><ul> <li>(1) Increased antistreptolysin O (ASO) titers > 400 Todd units</li><ul> <li>(a) Peak at 4 to 5 weeks after streptococcal pharyngitis</li><li>(b) High titers are supportive, but <i>not</i> diagnostic for RF.</li> </ul><li>(2) Increased anti-DNase B titers (less reliable than ASO titers)</li><li>(3) Throat cultures may or may not be positive.</li> </ul><li>Treatment for acute RF</li><ul> <li>(1) Bed rest</li><li>(2) Course of penicillin to eradicate throat carriage of group A streptococcus</li><ul> <li>Continue penicillin for years if severe carditis</li> </ul><li>(3) Aspirin with or without presence of a murmur</li><li>(4) Carditis and heart failure</li><ul> <li>Corticosteroids if murmur is present</li> </ul> </ul><li>Chronic RF</li><ul> <li>Monthly treatment with benzathine penicillin IM to prevent recurrences</li> </ul> </ol> </ol>
</div></html>
![[10.VI.A.Rheumatic fever (RF)]]
<<tiddler [[10.VI.A.Rheumatic fever (RF)]]>>
![[10.VI.B.Mitral valve stenosis]]
<<tiddler [[10.VI.B.Mitral valve stenosis]]>>
![[10.VI.C.Mitral valve regurgitation]]
<<tiddler [[10.VI.C.Mitral valve regurgitation]]>>
![[10.VI.D.Mitral valve prolapse]]
<<tiddler [[10.VI.D.Mitral valve prolapse]]>>
![[10.VI.E.Aortic valve (AV) stenosis]]
<<tiddler [[10.VI.E.Aortic valve (AV) stenosis]]>>
![[10.VI.F.Aortic valve regurgitation]]
<<tiddler [[10.VI.F.Aortic valve regurgitation]]>>
![[10.VI.G.Tricuspid valve (TV) regurgitation]]
<<tiddler [[10.VI.G.Tricuspid valve (TV) regurgitation]]>>
![[10.VI.H.Pulmonary valve (PV) stenosis]]
<<tiddler [[10.VI.H.Pulmonary valve (PV) stenosis]]>>
![[10.VI.I.Pulmonary valve regurgitation]]
<<tiddler [[10.VI.I.Pulmonary valve regurgitation]]>>
![[10.VI.J.Carcinoid heart disease]]
<<tiddler [[10.VI.J.Carcinoid heart disease]]>>
![[10.VI.K.Infective endocarditis (IE)]]
<<tiddler [[10.VI.K.Infective endocarditis (IE)]]>>
![[10.VI.L.Libman-Sacks endocarditis]]
<<tiddler [[10.VI.L.Libman-Sacks endocarditis]]>>
![[10.VI.M.Nonbacterial thrombotic endocarditis (marantic endocarditis)]]
<<tiddler [[10.VI.M.Nonbacterial thrombotic endocarditis (marantic endocarditis)]]>>
<html><a name="HC010023"></a> <br><a name="P010032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Etiology</li><ul> <li>Most often caused by recurrent attacks of rheumatic fever
<blockquote style="color: blue; ">MV stenosis: most common cause is recurrent RF</blockquote></li> </ul><li>Pathophysiology</li><ol type="a"> <li>Narrowing of the mitral valve orifice (<span>[[Fig. 10-14|Figure 10-14]]</span>)</li><li>Left atrium becomes dilated and hypertrophied</li><ul> <li>Due to increased work in filling the ventricle in diastole</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Dyspnea and hemoptysis with rust-colored sputum (heart failure cells)</li><ul> <li>Due to pulmonary capillary congestion and hemorrhage into the alveoli</li> </ul><li>Atrial fibrillation
<blockquote style="color: blue; ">Atrial fibrillation: common in mitral stenosis</blockquote></li><ul> <li>(1) Due to left atrial dilation and hypertrophy</li><li>(2) Intra-atrial thrombus develops due to stasis (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>).</li><ul> <li>Danger of systemic embolization</li> </ul> </ul><li>Pulmonary venous hypertension
<blockquote style="color: blue; ">MV stenosis: pulmonary venous hypertension; RHF</blockquote></li><ul> <li>(1) Due to chronic backup of atrial blood into the pulmonary vein</li><li>(2) Right-sided heart failure and right ventricular hypertrophy may occur.</li> </ul><li>Dysphagia for solids</li><ul> <li>(1) Left atrium is the most posteriorly located chamber in the heart.
<blockquote style="color: blue; ">Mitral stenosis: opening snap followed by an early to mid-diastolic rumble</blockquote></li><li>(2) Dilation of the left atrium compresses the esophagus.</li> </ul><li>Opening snap followed by an early to mid-diastolic rumble (see <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>)</li> </ol> </ol>
</div></html>
<html><a name="HC010024"></a> <br><a name="P010033"></a><div class="PA" style="color: black; "><ol type="1"> <li>Etiology</li><ol type="a"> <li>Mitral valve prolapse (most common cause)
<blockquote style="color: blue; ">Mitral valve prolapse: most common cause of mitral regurgitation</blockquote></li><li>Functional MV regurgitation (stretching of the MV ring)</li><ul> <li>Example-left-sided heart failure</li> </ul><li>Infective endocarditis</li><li>Rupture or dysfunction of the papillary muscle in acute MI</li><li>Acute rheumatic fever, Libman-Sacks endocarditis in systemic lupus erythematosus</li> </ol><li>Pathophysiology (<span>[[Fig. 10-15|Figure 10-15]]</span>)</li><ol type="a"> <li>Retrograde blood flow into the left atrium during systole</li><ul> <li>(1) Due to an incompetent MV or dilated MV ring</li><li>(2) Left atrium becomes dilated and hypertrophied</li> </ul><li>Volume overload in the left ventricle and left atrium leads to LHF.
<blockquote style="color: blue; ">MV regurgitation: pansystolic murmur; S<sub>3</sub>/S<sub>4</sub>; no ↑ intensity with deep held inspiration</blockquote></li> </ol><li>Clinical findings</li><ol type="a"> <li>Dyspnea, inspiratory crackles, and cough from LHF</li><li>Pansystolic murmur; S<sub>3</sub> and S<sub>4</sub> heart sounds (see <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>)</li> </ol> </ol>
</div></html>
<html><a name="HC010025"></a> <br><a name="P010034"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal dominant inheritance in some cases
<blockquote style="color: blue; ">MVP: association with Marfan and Ehlers-Danlos syndromes</blockquote></li><li>More common in women</li><li>Associated with Marfan and Ehlers-Danlos syndromes</li> </ol><li>Pathophysiology
<blockquote style="color: blue; ">MVP: myxomatous degeneration; excess dermatan sulfate</blockquote></li><ol type="a"> <li>Posterior bulging of the anterior and/or posterior leaflets into the left atrium during systole (<span>[[Fig. 10-16|Figure 10-16]]</span>)</li><li>Redundancy of valve tissue</li><ul> <li>(1) Myxomatous degeneration of the mitral valve leaflets</li><li>(2) Due to excess production of dermatan sulfate</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Most patients are asymptomatic.</li><li>Heart murmur</li><ul> <li>(1) Mid-systolic click
<blockquote style="color: blue; ">MVP: systolic click followed by murmur</blockquote></li><ul> <li>Due to sudden restraint by the chordae of the prolapsed valve</li> </ul><li>(2) Mid to late systolic regurgitant murmur follows the click.</li><li>(3) Decreased preload causes the click and murmur to move closer to the S<sub>1</sub> heart sound; examples:</li><ul> <li>(a) Anxiety</li><ul> <li>Increased heart rate decreases diastolic filling of left ventricle.</li> </ul><li>(b) Standing</li><ul> <li>Decreases venous return to the right side of the heart</li> </ul><li>(c) Valsalva maneuver (holding breath with epiglottis closed)</li><ul> <li>Positive intrathoracic pressure decreases venous return to the heart.
<blockquote style="color: blue; ">MVP: preload alters click and murmur relationship to S<sub>1</sub>/S<sub>2</sub></blockquote></li> </ul> </ul><li>(4) Increased preload causes the click and murmur to move closer to the S<sub>2</sub> heart sound; examples:</li><ul> <li>(a) Reclining</li><ul> <li>Increases venous return to the right side of the heart</li> </ul><li>(b) Squatting or sustained hand grip</li><ul> <li>Increases systemic vascular resistance, which impedes emptying of the left ventricle</li> </ul> </ul> </ul><li>Palpitations, chest pain, rupture of chordae producing acute MV regurgitation</li> </ol><li>Treatment in symptomatic patients
<blockquote style="color: blue; ">Symptomatic MVP: β-blockers</blockquote></li><ul> <li>β-Blocker decreases heart rate and force of contraction leading to less stretch and trauma to the prolapsed leaflets.</li> </ul> </ol>
</div></html>
<html><a name="HC010026"></a> <br><a name="P010035"></a><div class="PA" style="color: black; "><ol type="1"> <li>AV orifice is normally 3 cm<sup>2</sup>.</li><ol type="a"> <li>Symptoms appear when the orifice < 1 cm<sup>2</sup>.</li><li>Severe AV stenosis is present when the orifice < 0.5 cm<sup>2</sup>.</li> </ol><li>Etiology</li><ol type="a"> <li>Calcific AV stenosis of normal or bicuspid aortic valve (<span>[[Fig. 10-17|Figure 10-17]]</span>)
<blockquote style="color: blue; ">Calcific AV stenosis: most common cause in patients > 60 years old</blockquote></li><ul> <li>Most common cause of AV stenosis in patients > 60 years old</li> </ul><li>Congenital AV stenosis</li><ul> <li>Most common cause in patients < 30 years old</li> </ul><li>Age-related sclerosis of the aortic valve</li><li>Chronic rheumatic fever</li> </ol><li>Pathophysiology (<span>[[Fig. 10-18|Figure 10-18]]</span>)</li><ol type="a"> <li>Obstruction to left ventricular outflow during systole</li><li>Reduction in the aortic valve orifice area produces concentric LVH.</li> </ol><li>Clinical findings</li><ol type="a"> <li>Systolic ejection murmur; S<sub>4</sub> heart sound (see <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>)</li><li>Decreasing preload lessens the volume the left ventricle must eject.
<blockquote style="color: blue; ">AV stenosis: ejection murmur; S<sub>4</sub>; ↓ intensity with ↓ preload; ↑ intensity with ↑ preload</blockquote></li><ul> <li>Murmur intensity decreases.</li> </ul><li>Increasing preload increases the volume the left ventricle must eject.</li><ul> <li>Murmur intensity increases.</li> </ul><li>Opposite effect occurs in hypertrophic cardiomyopathy (see later).</li><li>Angina with exercise
<blockquote style="color: blue; ">AV stenosis: most common valvular lesion causing syncope and angina with exercise</blockquote></li><ul> <li>(1) Decreased blood flow through the stenotic valve leads to less filling of the coronary arteries during diastole.</li><li>(2) Subendocardium of concentrically hypertrophied heart receives less blood.</li> </ul><li>Syncope with exercise
<blockquote style="color: blue; ">AV stenosis: microangiopathic hemolytic anemia with schistocytes, hemoglobinuria</blockquote></li><ul> <li>Decreased blood flow through the stenotic valve leads to decreased blood flow to the brain.</li> </ul><li>Hemolytic anemia with schistocytes (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li><ul> <li>Indication for AV replacement</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC010027"></a> <br><a name="P010036"></a><div class="PA" style="color: black; "><ol type="1"> <li>Etiology</li><ol type="a"> <li>Isolated AV root dilation
<blockquote style="color: blue; ">Isolated AV root dilation: most common cause of aortic regurgitation</blockquote></li><li>Infective endocarditis</li><ul> <li>Most common infectious cause of acute AV regurgitation</li> </ul><li>Long-standing essential hypertension</li><li>Chronic rheumatic fever</li><li>Aortic dissection (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)</li><li>Coarctation</li><li>Syphilitic aortitis (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)</li><li>Aortitis in ankylosing spondylitis (refer to <span macro="tag [[23 Musculoskeletal and Soft Tissue Disorders]] [[Chapter 23]]"></span>)</li><li>Takayasu arteritis (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)</li> </ol><li>Pathophysiology (<span>[[Fig. 10-19|Figure 10-19]]</span>)</li><ol type="a"> <li>Retrograde blood flow into the left ventricle</li><ul> <li>(1) Due to an incompetent valve or dilated AV ring</li><li>(2) Decreases diastolic pressure</li><ul> <li>Due to drop in arterial volume as blood flows back into the left ventricle</li> </ul><li>(3) Volume overload of the left ventricle</li><ul> <li>Increases stroke volume (Frank-Starling mechanism)
<blockquote style="color: blue; ">AV regurgitation: ↑ pulse pressure</blockquote></li> </ul> </ul><li>Increased pulse pressure (difference between systolic and diastolic pressure)</li><ul> <li>Produces hyperdynamic circulation (e.g., bounding pulses)</li> </ul> </ol><li>Clinical findings
<blockquote style="color: blue; ">AV regurgitation: early diastolic murmur; bounding pulses; S<sub>3</sub>, S<sub>4</sub>; no ↑ intensity with inspiration</blockquote></li><ol type="a"> <li>Early diastolic murmur; S<sub>3</sub> and S<sub>4</sub> heart sounds (see <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>)</li><li>Signs of a hyperdynamic circulation are caused by a widened pulse pressure.</li><ul> <li>(1) Left ventricular volume markedly increases due to the incompetent valve.</li><li>(2) Frank-Starling mechanisms increase in stroke volume.
<blockquote style="color: blue; ">AV regurgitation: hyperdynamic circulation</blockquote></li><ul> <li>Increases systolic pressure</li> </ul><li>(3) Blood regurgitating into the left ventricle produces a drop in the diastolic blood pressure.</li><ul> <li>Recall that the diastolic blood pressure represents the amount of blood in the arterial system while the heart is filling up in diastole.</li> </ul><li>(4) An increase in systolic pressure plus a decrease in diastolic pressure widens the pulse pressure (difference between systolic pressure and diastolic pressure), which causes the hyperdynamic findings, including:</li><ul> <li>(a) Bounding pulses (Corrigan's water hammer pulse)</li><li>(b) Head nodding with systole (de Musset's sign)</li><li>(c) Pulsating nail bed with elevation of the nail (Quincke's pulse)</li> </ul> </ul><li>Austin Flint murmur
<blockquote style="color: blue; ">Austin Flint murmur: sign for AV replacement</blockquote></li><ul> <li>(1) Regurgitant stream from incompetent AV hits the anterior MV leaflet producing a diastolic murmur (functional mitral stenosis).</li><li>(2) Presence of this murmur indicates the need for replacement of the valve.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC010028"></a> <br><a name="P010037"></a><div class="PA" style="color: black; "><ol type="1"> <li>Etiology</li><ol type="a"> <li>Functional TV regurgitation (stretching of TV ring)</li><ul> <li>(1) Most common cause in adults
<blockquote style="color: blue; ">TV regurgitation: functional most common cause adults</blockquote></li><li>(2) Examples-RHF, pulmonary hypertension, dilated cardiomyopathy, right ventricular infarction</li> </ul><li>Congenital cardiac abnormalities</li><ul> <li>Most common cause in young adults</li> </ul><li>Infective endocarditis in intravenous drug abuse
<blockquote style="color: blue; ">TV regurgitation: infective endocarditis, carcinoid heart disease</blockquote></li><li>Carcinoid heart disease</li> </ol><li>Pathophysiology</li><ol type="a"> <li>Retrograde blood flow into the right atrium during systole</li><ul> <li>(1) Due to stretching of the valve ring or damage to the valve</li><li>(2) Causes right ventricular overload and RHF</li><li>(3) Causes right atrial dilation and hypertrophy</li> </ul><li>Produces volume overload in the right atrium and right ventricle</li> </ol><li>Clinical findings</li><ol type="a"> <li>Pulsating liver</li><ul> <li>Blood regurgitates into the venous system with systole.
<blockquote style="color: blue; ">TV regurgitation: pansystolic murmur; S<sub>3</sub>/S<sub>4</sub>; ↑ intensity with deep held inspiration</blockquote></li> </ul><li>Giant c-v wave jugular venous pulse (see <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>)</li><ul> <li>Sign of severe TV regurgitation</li> </ul><li>Pansystolic murmur; S<sub>3</sub> and S<sub>4</sub> heart sounds (see <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>)</li> </ol> </ol>
</div></html>
<html><a name="HC010029"></a> <br><a name="P010038"></a><div class="PA" style="color: black; "><ol type="1"> <li>Uncommon valvular lesion</li><li>Associated with carcinoid heart disease</li><li>Systolic ejection murmur (see <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>)</li><li>Right ventricular hypertrophy</li> </ol>
</div></html>
<html><a name="HC010030"></a> <br><a name="P010039"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most often a functional murmur from stretching of the PV ring
<blockquote style="color: blue; ">PV regurgitation: pulmonary hypertension</blockquote></li><ul> <li>Example-pulmonary hypertension (called a Graham Steell murmur)</li> </ul><li>Diastolic murmur; S<sub>3</sub> and S<sub>4</sub> heart sounds (see <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>)</li> </ol>
</div></html>
<html><a name="HC010031"></a> <br><a name="P010040"></a><div class="PA" style="color: black; "><ol type="1"> <li>Due to liver metastasis from a carcinoid tumor of small intestine (refer to <span macro="tag [[17 Gastrointestinal Disorders]] [[Chapter 17]]"></span>)</li><li>Serotonin causes fibrosis of the tricuspid and pulmonary valves.</li><ul> <li>Produces TV regurgitation and PV stenosis
<blockquote style="color: blue; ">Carcinoid heart disease: PV stenosis, TV regurgitation</blockquote></li> </ul> </ol>
</div></html>
<html><a name="HC010032"></a> <br><a name="P010041"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Risk factors for IE</li><ul> <li>(1) Diabetes mellitus, HIV infection</li><li>(2) Poor dental hygiene, congenital heart disease</li><li>(3) Mitral valve prolapse, aortic stenosis</li><li>(4) Hemodialysis, prosthetic heart valve</li><li>(5) Intravenous catheters, intravenous drug abuse (IVDA)</li> </ul><li>Microbial pathogens</li><ul> <li>(1) <i>Streptococcus viridans</i>
<blockquote style="color: blue; "><i>Streptococcus viridans:</i> most common cause of IE</blockquote></li><ul> <li>(a) Most common overall cause of IE (30-40% of cases)</li><li>(b) Typically produces subacute IE</li> </ul><li>(2) <i>Staphylococcus aureus</i></li><ul> <li>(a) Most common cause of IE in IVDA
<blockquote style="color: blue; "><i>Staphylococcus aureus:</i> most common pathogen producing IE in IV drug abuse</blockquote></li><li>(b) High mortality rate</li> </ul><li>(3) <i>Staphylococcus epidermidis</i></li><ul> <li>(a) Most common cause of IE after insertion of prosthetic valves</li><ul> <li>Usually occurs within 2 months of insertion
<blockquote style="color: blue; "><i>Staphylococcus epidermidis:</i> most common pathogen producing nosocomial and prosthetic valve IE</blockquote></li> </ul><li>(b) Most common cause of nosocomial endocarditis from intravenous catheters</li> </ul><li>(4) <i>Streptococcus bovis</i></li><ul> <li>Most common cause of IE in ulcerative colitis or colorectal cancer</li> </ul> </ul><li>Valves involved in IE</li><ul> <li>(1) Majority of valves involved are left-sided (>90%).</li><ul> <li>Right-sided valves with IE are usually associated with IVDA.
<blockquote style="color: blue; "><i>Streptococcus bovis:</i> most common pathogen producing IE in ulcerative colitis/colorectal cancer</blockquote></li> </ul><li>(2) Mitral valve</li><ul> <li>Most common overall valve involved in IE</li> </ul><li>(3) Tricuspid valve and aortic valve</li><ul> <li>Most common valves involved in IE due to IVDA
<blockquote style="color: blue; ">TV regurgitation in IVDA is due to infective endocarditis</blockquote></li> </ul> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Turbulent blood flow damages the valve → adherence of fibrin and platelets → trapping of circulating bacteria/fungi → proliferation of pathogens + laying down of fibrin to encase the vegetation</li><li><i>Streptococcus viridans</i> infects previously damaged valves.</li><li><i>Staphylococcus aureus</i> infects normal or previously damaged valves.</li> </ol><li>Pathology</li><ol type="a"> <li>Vegetations destroy the valve leaflet and chordae tendineae (<span>[[Fig. 10-20|Figure 10-20]]</span>).</li><li>Valve destruction leads to regurgitation murmurs.</li> </ol><li>Clinical findings</li><ol type="a"> <li>Fever is the most consistent sign (98% of cases).
<blockquote style="color: blue; ">IE: fever most consistent sign</blockquote></li><ul> <li>Common cause of fever of unknown origin</li> </ul><li>Immunocomplex vasculitis (if IE is subacute)</li><ul> <li>Examples-glomerulonephritis, Roth's spot (irregular red area with central white dot)</li> </ul><li>Microembolization findings
<blockquote style="color: blue; ">IE signs: microembolization, immunocomplex vasculitis</blockquote></li><ul> <li>(1) Splinter hemorrhages in nail beds (<span>[[Fig. 10-21|Figure 10-21]]</span>)</li><li>(2) Janeway's lesions (painless lesions on palms and feet)</li><li>(3) Osler's nodes (painful nodules on pads of the fingers or toes)</li><li>(4) Mucosal petechiae</li><li>(5) Infarctions in different tissue sites (e.g., digits, brain)</li> </ul><li>Splenomegaly (if IE is subacute)</li><li>Hematuria with RBC casts (glomerulonephritis)</li><li>Hematuria without RBC casts (infarction)</li> </ol><li>Laboratory findings
<blockquote style="color: blue; ">IE: positive blood culture majority of cases</blockquote></li><ol type="a"> <li>Positive blood cultures are present in 80% of cases.</li><ul> <li>Reflects the fact that many patients are taking antibiotics</li> </ul><li>Neutrophilic leukocytosis occurs in acute IE.</li><li>Monocytosis occurs in subacute bacterial endocarditis.</li><li>Mild anemia</li><ul> <li>Usually anemia of chronic disease</li> </ul><li>Transesophageal echocardiography</li><ul> <li>Useful in detecting vegetations on the valves</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Initial treatment is directed at the most likely organism.</li><li>Antibiotic after identification of the pathogen is guided by susceptibility testing.</li> </ol> </ol>
</div></html>
<html><a name="HC010033"></a> <br><a name="P010042"></a><div class="PA" style="color: black; "><ol type="1"> <li>Associated with systemic lupus erythematosus (SLE) in 30% to 50% of cases</li><li>Sterile vegetations are located over the mitral valve surface and chordae.
<blockquote style="color: blue; ">Libman-Sacks endocarditis: associated with SLE; MV involved</blockquote></li><ul> <li>Produces valve deformity and MV regurgitation</li> </ul> </ol>
</div></html>
<html><a name="HC010034"></a> <br><a name="P010043"></a><div class="PA" style="color: black; "><ol type="1"> <li>Paraneoplastic syndrome (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>)</li><li>Sterile, nondestructive vegetations on the mitral valve
<blockquote style="color: blue; ">Marantic endocarditis: sterile vegetations; paraneoplastic syndrome</blockquote></li><ul> <li>Procoagulant effect of circulating mucin from mucin-producing tumors of the colon/pancreas</li> </ul><li>Complications</li><ol type="a"> <li>Embolization</li><li>May be secondarily infected</li> </ol> </ol>
</div></html>
<html><a name="HC010036"></a> <br><a name="P010053"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Major cause of sudden death (15-20%) in adults < 40 years of age</li><li>Etiology</li><ul> <li>(1) Microbial pathogens</li><ul> <li>(a) Coxsackievirus (most common cause)
<blockquote style="color: blue; ">Coxsackievirus: most common cause of myocarditis and pericarditis</blockquote></li><li>(b) <i>Trypanosoma cruzi</i> (Chagas' disease)</li><ul> <li>Trypanosomes with flagella circulate in blood; amastigotes (no flagella) infect cardiac muscle.</li> </ul><li>(c) Lyme disease (<i>Borrelia burgdorferi</i>)
<blockquote style="color: blue; ">Chagas' disease: most common cause of myocarditis leading to CHF in Central/South America</blockquote></li> </ul><li>(2) Acute rheumatic fever</li><li>(3) Toxins</li><ul> <li>Examples-diphtheria, carbon monoxide</li> </ul><li>(4) Drugs
<blockquote style="color: blue; ">Drugs: doxorubicin, daunorubicin</blockquote></li><ul> <li>Examples-doxorubicin, daunorubicin, cocaine</li> </ul><li>(5) Collagen vascular</li><ul> <li>Examples-SLE, systemic sclerosis</li> </ul><li>(6) Sarcoidosis</li> </ul> </ol><li>Pathology</li><ol type="a"> <li>Global enlargement of the heart and dilation of all chambers</li><li>Lymphocytic infiltrate with focal areas of necrosis (<span>[[Fig. 10-22|Figure 10-22]]</span>)</li><ul> <li>Highly predictive of coxsackievirus</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Fever</li><li>Chest pain</li><li>Pericardial friction rub (see below)</li><li>Biventricular heart failure</li><li>Heart murmurs</li><ul> <li>MV regurgitation most common</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Increased CK-MB and troponins I and T
<blockquote style="color: blue; ">Myocarditis: ↑ CK-MB, troponins I and T</blockquote></li><li>Detection of antibodies of pathogens</li> </ol><li>Treatment</li><ol type="a"> <li>Treat the underlying cause.</li><li>Approximately 50% of patients will die within 5 years.</li> </ol> </ol>
</div></html>
<html><a name="HC010037"></a> <br><a name="P010054"></a><div class="PA" style="color: black; "><ol type="1"> <li>Etiology</li><ol type="a"> <li>Similar to disorders listed for myocarditis
<blockquote style="color: blue; ">Pericarditis: most common cause is coxsackievirus</blockquote></li><li>Coxsackievirus is the most common overall known cause.</li><ul> <li>Most are idiopathic, the cause unknown.</li> </ul> </ol><li>Pathology</li><ol type="a"> <li>Fibrinous type of pericardial exudate</li><ul> <li>Often accompanied by an effusion</li> </ul><li>Dense scar tissue with dystrophic calcification may cause constrictive pericarditis.</li> </ol><li>Clinical and laboratory findings</li><ol type="a"> <li>Tachycardia</li><li>Fever</li><li>Precordial chest pain
<blockquote style="color: blue; ">Pericarditis: precordial rub; pain relieved by leaning forward</blockquote></li><ul> <li>(1) Pain is relieved when leaning forward.</li><li>(2) Pain increases when leaning back.</li> </ul><li>Pericardial friction rub</li><ul> <li>(1) Scratchy, three-component rub (systole, early, and late diastole)</li><ul> <li>(a) Best heard with the patient leaning forward</li><li>(b) All three components are heard in ∼50% of cases.</li> </ul><li>(2) Does <i>not</i> disappear when the patient holds his breath</li> </ul><li>Serum CK-MB usually normal</li><li>Troponins I and T are increased in 35% to 50% of cases.</li><ul> <li>Usually indicates myocarditis present as well</li> </ul><li>Often accompanied by a pericardial effusion
<blockquote style="color: blue; ">Young woman with pericarditis and effusion: most likely has SLE</blockquote></li><ul> <li>(1) Muffled heart sounds</li><ul> <li>(a) Fluid surrounds the heart (<span>[[Fig. 10-23|Figure 10-23]]</span>).</li><li>(b) All pressures are equal in all chambers of the heart.</li> </ul><li>(2) Hypotension associated with pulsus paradoxus</li><ul> <li>(a) Drop in systolic blood pressure > 10 mm Hg during inspiration</li><li>(b) Inspiration increases the flow of venous blood into the right side of the heart (refer to <span>[[Box 10-1|BOX 10-1 CARDIAC PHYSICAL DIAGNOSIS]]</span>).</li><ul> <li>Increased pressure of blood in the right ventricle displaces the interventricular septum to the left causing a decrease in the left ventricular volume and a corresponding drop in systolic blood pressure.</li> </ul> </ul><li>(3) Neck vein distention on inspiration</li><ul> <li>(a) Blood cannot easily enter the right atrium, due to fluid surrounding the heart.</li><li>(b) Some blood refluxes back into the jugular vein (Kussmaul's sign).
<blockquote style="color: blue; ">Pericardial effusion on inspiration: neck vein distention, ↓ systolic blood pressure > 10 mm Hg</blockquote></li> </ul><li>(4) Chest radiograph shows a "water bottle" configuration (<span>[[Fig. 10-24|Figure 10-24]]</span>).</li> </ul><li>Constrictive pericarditis</li><ul> <li>(1) Etiology</li><ul> <li>(a) Tuberculosis is the most common cause worldwide.</li><li>(b) Most cases in the United States are idiopathic or secondary to scarring from previous open heart surgery.</li><li>(c) Pericardial calcification is seen on a chest radiograph in ∼25% of cases.
<blockquote style="color: blue; ">Constrictive pericarditis: incomplete filling of chambers; pericardial knock</blockquote></li> </ul><li>(2) Pathophysiology</li><ul> <li>Incomplete filling of the cardiac chambers due to thickening of the parietal pericardium</li> </ul><li>(3) Pericardial knock</li><ul> <li>Due to the ventricles hitting the thickened parietal pericardium</li> </ul> </ul> </ol><li>Treatment of pericarditis</li><ul> <li>Treat the underlying cause if it is known</li> </ul><li>Treatment of pericardial effusion</li><ul> <li>Pericardiocentesis to remove fluid</li> </ul> </ol>
</div></html>
![[10.VII.A.Myocarditis]]
<<tiddler [[10.VII.A.Myocarditis]]>>
![[10.VII.B.Pericarditis]]
<<tiddler [[10.VII.B.Pericarditis]]>>
<html><a name="HC010039"></a> <br><a name="P010058"></a><div class="PA" style="color: black; "><ul> <li>Group of diseases that primarily involve the myocardium and produce myocardial dysfunction</li> </ul>
</div></html>
<html><a name="HC010040"></a> <br><a name="P010059"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Cardiomyopathy: dilated, hypertrophic, restrictive</blockquote>
<ol type="1"> <li>Dilated (congestive)</li><li>Hypertrophic</li><li>Restrictive</li> </ol>
</div></html>
<html><a name="HC010041"></a> <br><a name="P010060"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common cardiomyopathy
<blockquote style="color: blue; ">Dilated cardiomyopathy: most common cardiomyopathy</blockquote></li><li>Etiology</li><ul> <li>(1) Idiopathic (most common)</li><li>(2) Genetic causes (25-35%)</li><li>(3) Myocarditis
<blockquote style="color: blue; ">Dilated cardiomyopathy: myocarditis most common cause</blockquote></li><ul> <li>Most common known cause; see Section VII</li> </ul><li>(4) Alcohol (15-40%)</li><ul> <li>Direct toxic effect or due to thiamine deficiency (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>)</li> </ul><li>(5) Drugs</li><ul> <li>Examples-doxorubicin, daunorubicin, cocaine
<blockquote style="color: blue; ">Dilated cardiomyopathy: doxorubicin, daunorubicin</blockquote></li> </ul><li>(6) Postpartum state</li><ul> <li>Last trimester or within 6 months postpartum</li> </ul><li>(7) Organic solvents ("glue sniffers heart")</li><li>(8) Acromegaly</li><li>(9) Myxedema heart in severe hypothyroidism</li> </ul> </ol><li>Pathophysiology</li><ol type="a"> <li>Decreased contractility</li><li>Systolic dysfunction type of LHF</li> </ol><li>Clinical findings</li><ol type="a"> <li>Global enlargement of the heart (<span>[[Fig. 10-25|Figure 10-25]]</span>)</li><ul> <li>(1) All chambers are dilated.</li><li>(2) Echocardiography shows poor contractility.
<blockquote style="color: blue; ">Dilated cardiomyopathy: global enlargement of heart</blockquote></li> </ul><li>Biventricular CHF</li><li>Heart murmurs (MV and TV regurgitation)</li><li>Left- and right-sided S<sub>3</sub> and S<sub>4</sub> heart sounds</li><li>Narrow pulse pressure</li><ul> <li>Due to decreased stroke volume</li> </ul><li>Arrhythmias</li><ul> <li>(1) Bundle branch blocks</li><li>(2) Atrial and ventricular arrhythmias</li> </ul><li>Ejection fraction is usually <40% (normal, ≥55%).</li> </ol><li>Treatment</li><ul> <li>If medical therapy is ineffective, cardiac transplantation is the only other option.</li> </ul> </ol>
</div></html>
![[10.VIII.A.Definition]]
<<tiddler [[10.VIII.A.Definition]]>>
![[10.VIII.B.Types of cardiomyopathy]]
<<tiddler [[10.VIII.B.Types of cardiomyopathy]]>>
![[10.VIII.C.Dilated cardiomyopathy]]
<<tiddler [[10.VIII.C.Dilated cardiomyopathy]]>>
![[10.VIII.D.Hypertrophic cardiomyopathy (HCM)]]
<<tiddler [[10.VIII.D.Hypertrophic cardiomyopathy (HCM)]]>>
![[10.VIII.E.Restrictive cardiomyopathy]]
<<tiddler [[10.VIII.E.Restrictive cardiomyopathy]]>>
<html><a name="HC010042"></a> <br><a name="P010061"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Hypertrophic cardiomyopathy: most common cause of sudden death in young individuals</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common cause of sudden death in young individuals</li><li>Familial form</li><ul> <li>(1) Most common form</li><li>(2) Autosomal dominant with nearly complete penetrance</li><li>(3) Occurs in young individuals</li><li>(4) Genes mapped to chromosome 14</li><ul> <li>(a) Missense mutation in 1 of at least 10 genes that code for proteins of cardiac sarcomeres</li><li>(b) Example-mutation in myosin heavy chain gene</li> </ul> </ul><li>Sporadic form</li><ul> <li>Occurs in elderly people</li> </ul> </ol><li>Pathophysiology</li><ol type="a"> <li>Hypertrophy of the myocardium</li><ul> <li>(1) Disproportionately greater hypertrophy of interventricular septum (IVS) than the free left ventricular wall.</li><li>(2) IVS hypertrophy may obstruct blood flow through the outflow tract.</li><li>(3) Most patients do <i>not</i> have severe obstruction of the outflow tract.
<blockquote style="color: blue; ">HCM: obstruction <i>below</i> the aortic valve</blockquote></li> </ul><li>Obstruction to blood flow, if present, is <i>below</i> the aortic valve.</li><ul> <li>As blood exits the left ventricle, the anterior leaflet of the mitral valve is drawn against the asymmetrically hypertrophied IVS (<span>[[Figs. 10-26|Figure 10-26]]</span> and <span>[[10-27|Figure 10-27]]</span>).</li> </ul><li>Aberrant myofibers are present in the conduction system; fatal arrhythmias</li><li>Left ventricle is noncompliant.</li><ul> <li>Muscle thickening restricts filling.</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Harsh systolic ejection murmur</li><ul> <li>Best heard along the left sternal border</li> </ul><li>Palpable double apical impulse
<blockquote style="color: blue; ">HCM: preload changes on murmur intensity opposite of those for AV stenosis</blockquote></li><li>Murmur intensity increases (obstruction worsens) with decreased preload.</li><ul> <li>Examples-standing up, Valsalva maneuver (increases positive intrathoracic pressure), use of inotropic drugs (e.g., digitalis)</li> </ul><li>Murmur intensity decreases (obstruction lessens) with increased preload.</li><ul> <li>(1) Examples-reclining, drugs decreasing cardiac contractility (e.g., β-blockers), sustained clenching of hands, squatting</li><li>(2) Increasing preload opens the outflow track.</li> </ul><li>Angina or syncope with exercise</li><ul> <li>Similar to aortic stenosis</li> </ul><li>Sudden death is due to ventricular tachycardia/fibrillation.
<blockquote style="color: blue; ">HCM: sudden death due to ventricular tachycardia/fibrillation</blockquote></li><ul> <li>Correlates with left ventricular wall thickness</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Avoid strenuous exertion.</li><li>Avoid drugs that decrease preload (e.g., diuretics) or increase force of contraction (e.g., digitalis).
<blockquote style="color: blue; ">HCM: Treat with β-blockers</blockquote></li><li>β-Blockers are the mainstay of therapy.</li><ul> <li>(1) Decreased heart rate prolongs diastole.</li><ul> <li>Increases preload</li> </ul><li>(2) Decrease myocardial contractility</li> </ul><li>Implantable cardioconvertor defibrillator</li><ul> <li>Prevents ventricular tachycardia/fibrillation and sudden cardiac death</li> </ul> </ol><li>Screen all first-degree relatives.</li><ol type="a"> <li>Two-dimensional echocardiography is used.</li><li>Screening for mutations is likely in the future.</li> </ol> </ol>
</div></html>
<html><a name="HC010043"></a> <br><a name="P010062"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Restrictive cardiomyopathy: least common cardiomyopathy; low-voltage ECG</blockquote>
<ol type="1"> <li>Etiology</li><ol type="a"> <li>Most frequently caused by the following:</li><ul> <li>(1) Amyloidosis</li><li>(2) Myocardial fibrosis after open-heart surgery</li><li>(3) Radiation</li> </ul><li>Infiltrative diseases</li><ul> <li>Examples-Pompe's glycogenosis, hemochromatosis</li> </ul><li>Endocardial fibroelastosis in a child</li><ul> <li>Thick fibroelastic tissue in the endocardium</li> </ul><li>Sarcoidosis</li><li>Systemic sclerosis</li> </ol><li>Pathophysiology
<blockquote style="color: blue; ">Restrictive cardiomyopathy: ↓ ventricular compliance</blockquote></li><ol type="a"> <li>Decreased ventricular compliance</li><li>Diastolic dysfunction type of LHF</li> </ol><li>Clinical findings</li><ol type="a"> <li>Progressive LHF and RHF</li><li>ECG is low voltage with ST-T wave changes.</li> </ol><li>Treatment</li><ol type="a"> <li>Treat the underlying cause.</li><ul> <li>Examples-treat hemochromatosis with phlebotomy; treat sarcoidosis with corticosteroids</li> </ul><li>No effective therapy for most causes</li> </ol> </ol>
</div></html>
<html><a name="HC011002"></a> <br><a name="PB011001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>EPO</b> increases the O<sub>2</sub>-carrying capacity of blood by stimulating erythroid stem cells to divide. Epoetin alfa, a form of EPO produced by recombinant DNA technology, is frequently abused by athletes to increase their energy level. It also is used in the treatment of anemia associated with renal failure, chronic disease, and chemotherapy.</div><a name="P011002"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">EPO: synthesized by interstitial cells in peritubular capillary bed</blockquote>
<ol type="1"> <li>Primarily synthesized in the renal cortex by interstitial cells in the peritubular capillary bed</li><li>Stimuli for EPO release
<blockquote style="color: blue; ">Stimuli for EPO: hypoxemia, left-shifted OBC, high altitude</blockquote></li><ul> <li>Hypoxemia, severe anemia, left-shifted O<sub>2</sub>-binding curve (OBC), high altitude</li> </ul><li>Increased O<sub>2</sub> content suppresses EPO release (e.g., polycythemia vera).</li><li>Other sources of EPO</li><ul> <li>Ectopic production by renal cell carcinoma and hepatocellular carcinoma</li> </ul><li>Peripheral blood markers of erythropoiesis</li><ol type="a"> <li>Reticulocytes are newly released RBCs from the bone marrow.</li><li>Identified with supravital stains</li><ul> <li>Detect thread-like RNA filaments in the cytoplasm (<span>[[Fig. 11-1|Figure 11-1]]</span>)</li> </ul><li>In 24 hours, they become mature RBCs.</li> </ol> </ol>
</div></html>
<html><a name="HC011003"></a> <br><a name="P011003"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Reticulocyte count: measure of effective erythropoiesis</blockquote>
<ol type="1"> <li>Marker of effective erythropoiesis</li><ul> <li>Bone marrow response to anemia</li> </ul><li>Develop into a mature RBC in 24 hours</li><ul> <li>Maturation occurs with the help of splenic macrophages.</li> </ul><li>Reticulocyte count is reported as a percentage (normal < 3%).
<blockquote style="color: blue; ">Reticulocyte count: must correct for degree of anemia.</blockquote></li><ol type="a"> <li>Percentage count is falsely increased in anemia (<span>[[Fig. 11-2|Figure 11-2]]</span>).</li><li>Initial percentage must be corrected for the degree of anemia.</li><li>Corrected reticulocyte count = (actual Hct/45) × reticulocyte count, where 45 represents the normal hematocrit (Hct)
<blockquote style="color: blue; ">Correction: Hct/45 × reticulocyte count</blockquote></li><li>Example</li><ul> <li>(1) Hct 15%, reticulocyte count 18%</li><li>(2) Corrected reticulocyte count is 6% (15/45 × 18% = 6%)</li> </ul><li>Additional correction is required if RBC polychromasia is present.
<blockquote style="color: blue; ">Polychromasia: divide original correction by 2</blockquote></li><ul> <li>(1) Polychromatic RBCs are even younger RBCs than reticulocytes (<span>[[Fig. 11-3|Figure 11-3]]</span>).</li><li>(2) Appear when there is a very brisk hemolytic anemia</li><li>(3) Require 2 to 3 days before becoming mature RBCs</li><li>(4) Falsely increase the initial reticulocyte count, because they have RNA filaments and are counted as reticulocytes</li><li>(5) Correction is made by dividing the initial reticulocyte count corrected for the degree of anemia by 2.</li><ul> <li>In the above example, if polychromasia was present, the additional correction would be 6%/2 = 3%, which is still a good response to anemia.</li> </ul> </ul> </ol><li>Corrected reticulocyte count ≥ 3%
<blockquote style="color: blue; ">Corrected reticulocyte count: <3% ineffective erythropoiesis; ≥3% effective erythropoiesis</blockquote></li><ol type="a"> <li>Good bone marrow response to anemia (i.e., effective erythropoiesis)</li><li>Examples-hemolytic anemia; after treatment of iron deficiency with iron</li> </ol><li>Corrected reticulocyte count < 3%</li><ol type="a"> <li>Poor bone marrow response to anemia (i.e., ineffective erythropoiesis)</li><li>Examples-untreated iron deficiency; aplastic anemia</li> </ol> </ol>
</div></html>
<html><a name="HC011004"></a> <br><a name="P011004"></a><div class="PA" style="color: black; "><ul> <li>RBC, WBC, and platelet production that occurs outside the bone marrow</li><ol type="1"> <li>Common sites of EMH are the liver and spleen.
<blockquote style="color: blue; ">EMH: most often occurs in the liver and spleen</blockquote></li><li>Pathogenesis</li><ol type="a"> <li>Intrinsic bone marrow disease (e.g., myelofibrosis)</li><li>Accelerated erythropoiesis (e.g., severe hemolysis in sickle cell disease)</li><ul> <li>(1) Expands the bone marrow cavity</li><li>(2) Radiograph of the skull shows a "hair-on-end" appearance (<span>[[Fig. 11-4|Figure 11-4]]</span>).</li> </ul> </ol><li>EMH produces hepatosplenomegaly.
<blockquote style="color: blue; ">EMH: hepatosplenomegaly</blockquote></li> </ol> </ul>
</div><a name="PB011002"></a><div class="BB" style="color: rgb(47, 79, 79); ">In the fetus, hematopoiesis (blood cell formation) begins in the yolk sac and subsequently moves to the liver and finally the bone marrow by the fifth to sixth months of gestation.</div></html>
![[11.I.A.Erythropoiesis and erythropoietin (EPO)]]
<<tiddler [[11.I.A.Erythropoiesis and erythropoietin (EPO)]]>>
![[11.I.B.Reticulocyte count]]
<<tiddler [[11.I.B.Reticulocyte count]]>>
![[11.I.C.Extramedullary hematopoiesis (EMH)]]
<<tiddler [[11.I.C.Extramedullary hematopoiesis (EMH)]]>>
<html><a name="HC011006"></a> <br><a name="P011009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hemoglobin (Hb), Hct, RBC count</li><li>RBC indices, RBC distribution width (RDW)</li><li>WBC count with a differential count, platelet count</li><li>Evaluation of the peripheral blood morphology</li> </ol>
</div></html>
<html><a name="HC011007"></a> <br><a name="PB011003"></a><div class="BB" style="color: rgb(47, 79, 79); ">Fetal RBCs containing HbF are destroyed by splenic macrophages over the ensuing 6 to 9 months. The unconjugated bilirubin derived from the initial destruction of fetal RBCs is responsible for physiologic jaundice of the newborn, which occurs ∼3 days from birth.</div><a name="P011010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Factors affecting the normal range (reference interval)</li><ol type="a"> <li>Premature newborns</li><ul> <li>(1) Variable Hb concentration depending on gestational age</li><li>(2) Anemia in prematurity
<blockquote style="color: blue; ">Anemia prematurity: loss of iron from mother; blood loss from venipuncture</blockquote></li><ul> <li>(a) Iron deficiency</li><ul> <li>Due to loss of the daily supply of iron from mother's iron stores</li> </ul><li>(b) Blood loss from excessive venipunctures</li> </ul> </ul><li>Newborns</li><ul> <li>(1) Newborns have higher normal ranges than do infants and children.</li><li>(2) HbF (2α/2γ globin chains) shifts the OBC to the left causing the release of EPO.</li><ul> <li>EPO causes an increase in Hb, Hct, and RBC count.
<blockquote style="color: blue; ">Fetal Hb: left-shifts OBC causing an increase in Hb</blockquote></li> </ul><li>(3) After birth, the Hb drops from ∼18.5 to 11 g/dL (physiologic anemia).</li><li>(4) HbF-containing cells are replaced by RBCs containing HbA (>97%), HbA<sub>2</sub> (<2.5%), and HbF (<1%).</li> </ul><li>Children
<blockquote style="color: blue; ">Children: more right-shifted OBCs than adults</blockquote></li><ul> <li>(1) Have a lower Hb concentration than adults</li><li>(2) Due to higher serum phosphorus levels</li><ul> <li>(a) Increased serum phosphorus increases synthesis of 2,3-bisphosphoglycerate (BPG).</li><li>(b) Increased 2,3-BPG right-shifts the OBC.</li><li>(c) Greater release of O<sub>2</sub> to tissue overrides the need to have a higher Hb.</li> </ul> </ul><li>Adult men and women
<blockquote style="color: blue; ">Anemia in adult male: <13.5 g/dL</blockquote></li><ul> <li>(1) Men have higher Hb levels than women.</li><ul> <li>(a) Due to increased testosterone</li><ul> <li>Stimulates erythropoiesis</li> </ul><li>(b) Due to lack of cyclic bleeding</li> </ul><li>(2) Anemia in an adult male is an Hb < 13.5 g/dL.
<blockquote style="color: blue; ">Anemia in nonpregnant female: <12.5 g/dL</blockquote></li><li>(3) Anemia in a nonpregnant woman is an Hb < 12.5 g/dL.</li> </ul><li>Pregnancy</li><ul> <li>(1) Pregnant women have lower normal ranges than nonpregnant women.</li><ul> <li>(a) Due to an increase in plasma volume and RBC mass (i.e., more RBCs are produced).
<blockquote style="color: blue; ">Pregnancy: 2× greater increase in plasma volume than RBC mass</blockquote></li><li>(b) Plasma volume is twice greater than RBC mass causing a slight decrease in Hb (dilutional effect).</li> </ul><li>(2) In a pregnant woman, anemia is a Hb < 11 g/dL.</li> </ul> </ol><li>Changes in thalassemia (i.e., a genetic globin chain disorder)</li><ol type="a"> <li>Hb and Hct are decreased.</li><li>RBC count is increased.
<blockquote style="color: blue; ">Thalassemia: ↓ Hb, Hct; ↑ RBC count; MCV/RBC < 13</blockquote></li><li>Mean corpuscular volume (MCV)/RBC count ratio < 13.</li> </ol><li>Anemia</li><ol type="a"> <li>Decrease in Hb, Hct, or RBC concentration</li><li>O<sub>2</sub> saturation and Pa<span style="font-variant:small-caps;">o</span><sub>2</sub> are normal; decreased O<sub>2</sub> content (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>).
<blockquote style="color: blue; ">Anemia: O<sub>2</sub> saturation and arterial P<span style="font-variant:small-caps;">o</span><sub>2</sub> normal</blockquote></li><li>Sign of an underlying disease rather than a specific diagnosis</li><li>General clinical findings
<blockquote style="color: blue; ">Anemia: sign of disease; not a specific diagnosis</blockquote></li><ul> <li>(1) Fatigue</li><li>(2) Dyspnea with exertion
<blockquote style="color: blue; ">Anemia: ↓ O2 content</blockquote></li><li>(3) Inability to concentrate</li><li>(4) Dizziness</li><li>(5) Pulmonary flow murmur</li><ul> <li>Decreased blood viscosity in severe anemia</li> </ul><li>(6) Pallor of skin, conjunctivae, palmar creases</li><ul> <li>Indications of severe anemia</li> </ul><li>(7) High-output cardiac failure</li><ul> <li>Decreased blood viscosity in severe anemia (<5 g/dL)</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC011008"></a> <br><a name="P011011"></a><div class="PA" style="color: black; "><ol type="1"> <li>MCV
<blockquote style="color: blue; ">MCV: classification of anemias</blockquote></li><ol type="a"> <li>Average volume of RBCs</li><li>Used to classify anemia (<span>[[Fig. 11-5|Figure 11-5]]</span>)</li><ul> <li>(1) Microcytic (<80 μm<sup>3</sup>)</li><li>(2) Normocytic (80-100 μm<sup>3</sup>)</li><li>(3) Macrocytic (>100 μm<sup>3</sup>)</li> </ul> </ol><li>Mean corpuscular hemoglobin concentration (MCHC)</li><ol type="a"> <li>Average Hb concentration in RBCs (<span>[[Fig. 11-6|Figure 11-6]]</span>)</li><li>Decreased MCHC</li><ul> <li>(1) Correlates with decreased synthesis of Hb</li><ul> <li>Example-all the microcytic anemias</li> </ul><li>(2) Central area of pallor is greater than normal.</li><ul> <li>Called hypochromasia (see <span>[[Fig. 11-11|Figure 11-11]]</span>)</li> </ul> </ul><li>Increased MCHC
<blockquote style="color: blue; ">MCHC: ↓ in microcytic anemias; ↑ in spherocytosis</blockquote></li><ul> <li>(1) Correlates with the presence of spherical RBCs</li><ul> <li>Example-hereditary spherocytosis (see <span>[[Fig. 11-25|Figure 11-25]]</span>)</li> </ul><li>(2) RBCs lack the central area of pallor.</li> </ul> </ol><li>RDW
<blockquote style="color: blue; ">RDW: measure of size variation of RBCs</blockquote></li><ol type="a"> <li>Reflects variation in size of peripheral blood RBCs</li><ul> <li>(1) Size variation is called anisocytosis.</li><li>(2) RDW is significant only if it is increased.</li> </ul><li>Increased if RBCs are <i>not</i> uniformly the same size</li><ul> <li>Example-mixture of microcytic and normocytic cells</li> </ul><li>Iron deficiency
<blockquote style="color: blue; ">Iron deficiency: ↑ RDW</blockquote></li><ul> <li>(1) Only microcytic anemia with an increased RDW</li><li>(2) Due to a mixture of normocytic and microcytic RBCs</li> </ul> </ol> </ol>
</div></html>
![[11.II.A.Components of a CBC]]
<<tiddler [[11.II.A.Components of a CBC]]>>
![[11.II.B.Hb, Hct, and RBC counts]]
<<tiddler [[11.II.B.Hb, Hct, and RBC counts]]>>
![[11.II.C.RBC indices]]
<<tiddler [[11.II.C.RBC indices]]>>
![[11.II.D.Characteristics of mature RBCs]]
<<tiddler [[11.II.D.Characteristics of mature RBCs]]>>
![[11.II.E.WBC count and differential]]
<<tiddler [[11.II.E.WBC count and differential]]>>
![[11.II.F.Platelet count]]
<<tiddler [[11.II.F.Platelet count]]>>
![[11.II.G.Iron studies (Fig. 11-7)]]
<<tiddler [[11.II.G.Iron studies (Fig. 11-7)]]>>
![[11.II.H.Hb electrophoresis]]
<<tiddler [[11.II.H.Hb electrophoresis]]>>
<html><a name="HC011009"></a> <br><a name="P011012"></a><div class="PA" style="color: black; "><ol type="1"> <li>Lack mitochondria; therefore:</li><ol type="a"> <li>No citric acid cycle</li><li>No β-oxidation of fatty acids</li><li>No ketone body synthesis</li> </ol><li>Anaerobic glycolysis</li><ol type="a"> <li>Main source of adenosine triphosphate (ATP)
<blockquote style="color: blue; ">Mature RBC: anaerobic glycolysis; lactic acid end-product</blockquote></li><li>Lactic acid is the end-product of RBC metabolism.</li><ul> <li>(1) Converted by the liver into glucose via gluconeogenesis</li><li>(2) Glucose is utilized by RBCs for synthesizing ATP.
<blockquote style="color: blue; ">Cori cycle: lactic acid converted to glucose in liver→ glucose to RBC</blockquote></li><ul> <li>This is called the Cori cycle.</li> </ul> </ul> </ol><li>Pentose phosphate pathway</li><ol type="a"> <li>Synthesizes glutathione (GSH)</li><ul> <li>Antioxidant that neutralizes hydrogen peroxide (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>)</li> </ul><li>Hydrogen peroxide is a product of oxidative metabolism.
<blockquote style="color: blue; ">GSH: neutralizes peroxide and other free radicals</blockquote></li> </ol><li>Methemoglobin reductase pathway (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li><ol type="a"> <li>Methemoglobin (metHb) refers to heme iron that is oxidized (Fe<sup>+3</sup>).</li><ul> <li>MetHb <i>cannot</i> bind O<sub>2</sub>.</li> </ul><li>Reductase system converts iron to ferrous (Fe<sup>+2</sup>) so that the RBCs can bind O<sub>2</sub>.
<blockquote style="color: blue; ">MetHb reductase: reduces Fe<sup>+3</sup> to Fe<sup>+2</sup></blockquote></li> </ol><li>Luebering-Rapaport pathway</li><ol type="a"> <li>Synthesizes 2,3-BPG</li><li>Required to right-shift the OBC (i.e., release O<sub>2</sub> to tissue; refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)
<blockquote style="color: blue; ">2,3-BPG: product of the glycolytic cycle</blockquote></li> </ol><li>Senescent RBCs</li><ol type="a"> <li>Phagocytosed in the cords of Billroth by splenic macrophages</li><li>Heme degradation by macrophages produces unconjugated bilirubin.</li> </ol><li>Lack human leukocyte antigens on their membranes (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>)
<blockquote style="color: blue; ">Unconjugated bilirubin: end-product of heme degradation in macrophages</blockquote></li> </ol>
</div></html>
<html><a name="HC011010"></a> <br><a name="PB011004"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>A 100 cell differential count</b> divides leukocytes by percentage (neutrophils, lymphocytes, etc.) and further subdivides neutrophils into segmented and band neutrophils. Multiplication of the percentage times the total white blood cell count gives the absolute number of a particular leukocyte. Example-lymphocytes 30%, total WBC count 10,000/mm<sup>3</sup>. Absolute lymphocyte count is 0.30 × 10,000 = 3000/mm<sup>3</sup>.</div></html>
<html><a name="HC011011"></a> <br><a name="P011014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Platelets are anucleate cells.</li><li>They are derived from cytoplasmic budding of megakaryocytes.</li><li>Platelets and their disorders are discussed in <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>.</li> </ol>
</div></html>
<html><a name="HC011012"></a><span>[[Fig. 11-7|Figure 11-7]]</span> <br> <br><a name="P011015"></a><div class="PA" style="color: black; "><ol type="1"> <li>Serum ferritin</li><ol type="a"> <li>Ferritin is a soluble iron-binding storage protein.
<blockquote style="color: blue; ">Ferritin: synthesized in bone marrow macrophages</blockquote></li><ul> <li>(1) Primary storage site is in the bone marrow macrophages.</li><ul> <li>See shaded area in the small box in <span>[[Figure 11-7A|Figure 11-7]]</span>.</li> </ul><li>(2) Serum levels directly correlate with ferritin stores in the macrophages.</li><li>(3) Synthesis of ferritin in macrophages increases in inflammation.</li> </ul><ul> <li>Due to release of interleukin 1 and tumor necrosis factor-α</li> </ul><li>Decreased serum ferritin</li><ul> <li>Diagnostic of iron deficiency (see <span>[[Fig. 11-7B|Figure 11-7]]</span>)</li> </ul><li>Increased serum ferritin
<blockquote style="color: blue; ">Serum ferritin: ↓ iron deficiency; ↑ ACD, iron overload disease</blockquote></li><ul> <li>(1) Anemia of chronic disease (ACD) (<span>[[Fig. 11-7C|Figure 11-7]]</span>)</li><li>(2) Iron overload disease (<span>[[Fig. 11-7D|Figure 11-7]]</span>)</li> </ul><li>Hemosiderin</li><ul> <li>(1) Insoluble degradation product of ferritin</li><li>(2) Decreased and increased levels correlate with changes in ferritin stores.</li> </ul> </ol><li>Serum iron</li><ol type="a"> <li>Represents iron bound to transferrin</li><ul> <li>(1) Binding protein of iron</li><li>(2) Synthesized in the liver</li> </ul><li>Serum iron is the shaded area of the column in <span>[[Figure 11-7A|Figure 11-7]]</span>.</li><ul> <li>Note that the normal serum iron level is ∼100 μg/dL.</li> </ul><li>Decreased serum iron</li><ul> <li>(1) Iron deficiency (see <span>[[Fig. 11-7B|Figure 11-7]]</span>)</li><li>(2) ACD (see <span>[[Fig. 11-7C|Figure 11-7]]</span>).</li> </ul><li>Increased serum iron</li><ul> <li>(1) Iron overload diseases (see <span>[[Fig. 11-7D|Figure 11-7]]</span>)</li><li>(2) Examples-sideroblastic anemia, hemochromatosis
<blockquote style="color: blue; ">Serum iron: ↓ iron deficiency, ACD; ↑ iron overload disease</blockquote></li> </ul> </ol><li>Serum total iron-binding capacity (TIBC)</li><ol type="a"> <li>Serum TIBC correlates with the concentration of transferrin.
<blockquote style="color: blue; ">↓ TIBC = ↓ transferrin; ↑ TIBC = ↑ transferrin</blockquote></li><ul> <li>(1) Height of the column in <span>[[Figure 11-7A|Figure 11-7]]</span> correlates with serum transferrin and TIBC.</li><li>(2) Note that the normal TIBC is ∼300 μg/dL.</li> </ul><li>Relationship of transferrin synthesis with ferritin stores in macrophages</li><ul> <li>(1) Decreased ferritin stores cause increased liver synthesis of transferrin (see <span>[[Fig. 11-7B|Figure 11-7]]</span>).</li><ul> <li>Increase in transferrin and TIBC is present in iron deficiency.</li> </ul><li>(2) Increased ferritin stores causes decreased liver synthesis of transferrin (see <span>[[Fig. 11-7C and D|Figure 11-7]]</span>).
<blockquote style="color: blue; ">↓ Ferritin stores = ↑ TIBC; iron deficiency; ↑ ferritin stores = ↓ TIBC; ACD, iron overload</blockquote></li><ul> <li>Decrease in transferrin and TIBC occurs in ACD (see <span>[[Fig. 11-7C|Figure 11-7]]</span>) and iron overload disease (see <span>[[Fig. 11-7D|Figure 11-7]]</span>).</li> </ul> </ul> </ol><li>Iron saturation (%)</li><ol type="a"> <li>Percentage of binding sites on transferrin occupied by iron</li><ul> <li>(1) Iron saturation (%) = serum iron/TIBC × 100</li><li>(2) In <span>[[Figure 11-7A|Figure 11-7]]</span>, the normal % saturation is 100/300 × 100, or 33%.</li> </ul><li>Decreased iron saturation</li><ul> <li>(1) Iron deficiency (see <span>[[Fig. 11-7B|Figure 11-7]]</span>)
<blockquote style="color: blue; ">↓ Iron saturation: iron deficiency, ACD; ↑ iron saturation: iron overload disease</blockquote></li><li>(2) ACD (see <span>[[Fig. 11-7C|Figure 11-7]]</span>)</li> </ul><li>Increased iron saturation</li><ul> <li>Iron overload disease (see <span>[[Fig. 11-7D|Figure 11-7]]</span>)</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC011013"></a> <br><a name="P011016"></a><div class="PA" style="color: black; "><ol type="1"> <li>Used to detect hemoglobinopathies (<span>[[Fig. 11-8|Figure 11-8]]</span>).</li><ol type="a"> <li>Abnormality in globin chain structure (e.g., sickle cell disease)</li><li>Abnormality in globin chain synthesis (e.g., thalassemia)</li> </ol><li>Types of normal Hb detected (<span>[[Fig. 11-8A|Figure 11-8]]</span>)</li><ol type="a"> <li>HbA has 2α/2β globin chains (97% in adults).
<blockquote style="color: blue; ">HbA: 2α/2β</blockquote></li><li>HbA<sub>2</sub> has 2α/2δ globin chains (2% in adults).
<blockquote style="color: blue; ">HbA<sub>2</sub>: 2α/2δ</blockquote></li><li>HbF has 2α/2γ globin chains (1% in adults).
<blockquote style="color: blue; ">HbF: 2α/2γ</blockquote></li> </ol><li>Examples of abnormal Hb detected</li><ul> <li>Sickle Hb, HbH, Hb Bart</li> </ul> </ol>
</div></html>
<html><a name="HC011015"></a> <br><a name="P011020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Iron deficiency (most common)</li><li>Anemia of chronic disease (ACD)</li><li>Thalassemia (α and β)</li><li>Sideroblastic anemias (least common)</li> </ol>
</div></html>
<html><a name="HC011016"></a><span>[[Fig. 11-9|Figure 11-9]]</span> <br> <br><a name="P011021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Defects in the synthesis of Hb</li><ul> <li>Hb =heme + globin chains
<blockquote style="color: blue; ">Microcytic anemias: defects in the synthesis of Hb (heme + globin chains)</blockquote></li> </ul><li>Defects in the synthesis of heme (i.e., iron + protoporphyrin)</li><ul> <li>Iron deficiency, ACD, sideroblastic anemias</li> </ul><li>Defects in the synthesis of globin chains (i.e., α or β)</li><ul> <li>α-Thalassemia, β-thalassemia (thal)</li> </ul> </ol>
</div></html>
<html><a name="HC011017"></a> <br><a name="PB011005"></a><div class="BB" style="color: rgb(47, 79, 79); ">The <b>stages of iron deficiency</b> in sequence are as follows: absent iron stores; decreased serum ferritin; decreased serum iron, increased TIBC, decreased iron saturation; normocytic normochromic anemia; microcytic hypochromic anemia.</div><a name="P011022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Iron reabsorption
<blockquote style="color: blue; ">Types of iron: reduced Fe<sup>+2</sup> (heme iron in meat), oxidized Fe<sup>+3</sup> (nonheme iron in plants)</blockquote></li><ol type="a"> <li>Approximately 10% of dietary iron (1-2 mg/day) is reabsorbed in the duodenum.</li><ul> <li>(1) Iron from plants is in a nonheme, oxidized form (ferric, Fe<sup>+3</sup>).</li><ul> <li>Oxidized form <i>cannot</i> be reabsorbed in the duodenum.</li> </ul><li>(2) Iron from meat is in a heme, reduced form (ferrous, Fe<sup>+2</sup>)</li><ul> <li>Reduced form is directly reabsorbed in the duodenum.
<blockquote style="color: blue; ">Oxidized Fe<sup>+3</sup> must be reduced to Fe<sup>+2</sup> for reabsorption in duodenum</blockquote></li> </ul> </ul><li>Percentage of iron reabsorbed from the diet is increased in the following:</li><ul> <li>(1) Normal women who have cyclic bleeding</li><li>(2) Pregnancy and lactation</li><li>(3) Any anemia, regardless of type</li><ul> <li>Danger of iron overload, if iron supplements are improperly prescribed</li> </ul> </ul><li>Most of the iron is attached to the four heme groups in Hb; the remainder is stored in the following:</li><ul> <li>(1) Marrow macrophages
<blockquote style="color: blue; ">Iron: majority stored in marrow macrophages</blockquote></li><ul> <li>Approximately 1000 mg in men and 400 mg in women</li> </ul><li>(2) Myoglobin</li><ul> <li>Contains one heme group</li> </ul><li>(3) Enzymes, as a cofactor</li> </ul><li>Gastric acid frees elemental iron from heme and nonheme products.</li><ul> <li>Underscores why achlorhydria (absent stomach acid) decreases availability of iron for reabsorption</li> </ul><li>Ascorbic acid is important in iron reabsorption.
<blockquote style="color: blue; ">Ascorbic acid: reduces nonheme iron to Fe<sup>+2</sup></blockquote></li><ul> <li>Reduces Fe<sup>+3</sup> in nonheme foods to the absorbable Fe<sup>+2</sup></li> </ul><li>Maintenance of iron homeostasis</li><ul> <li>(1) Regulation of the amount of iron reabsorbed</li><ul> <li>(a) HFE (hemochromatosis) gene product facilitates binding of plasma transferrin with its mucosal cell transferrin receptor.</li><ul> <li>This allows transferrin to be endocytosed (reabsorbed) by intestinal cells.</li> </ul><li>(b) Amount of endocytosed transferrin determines how much mucosal cell iron is released into the plasma to bind with transferrin.</li> </ul> </ul> </ol><li>Epidemiology of iron deficiency
<blockquote style="color: blue; ">Iron deficiency: most common overall anemia</blockquote></li><ol type="a"> <li>It is the most common anemia.</li><li>Most common nutritional deficiency worldwide</li><li>Greatest prevalence</li><ul> <li>(1) Toddlers ages 1 to 2 years old</li><ul> <li>Due to inadequate intake</li> </ul><li>(2) Females ages 12 to 49 years old</li><ul> <li>Due to menstrual loss</li> </ul> </ul><li>Causes of iron deficiency (<span>[[Table 11-1|Table 11-1. CAUSES OF IRON DEFICIENCY ANEMIA]]</span>)</li> </ol><li>Pathogenesis
<blockquote style="color: blue; ">Iron deficiency: most commonly caused by bleeding</blockquote></li><ul> <li>Decreased synthesis of heme (see <span>[[Fig. 11-9|Figure 11-9]]</span>)</li> </ul><li>Clinical and laboratory findings</li><ol type="a"> <li>Plummer-Vinson syndrome</li><ul> <li>(1) Caused by chronic iron deficiency</li><li>(2) Esophageal web</li><ul> <li>Dysphagia for solids but <i>not</i> liquids
<blockquote style="color: blue; ">Koilonychia: spoon nails; sign of iron deficiency</blockquote></li> </ul><li>(3) Achlorhydria</li><ul> <li>Absent acid in the stomach</li> </ul><li>(4) Glossitis</li><ul> <li>Inflammation of the tongue</li> </ul><li>(5) Spoon nails (koilonychia; <span>[[Fig. 11-10|Figure 11-10]]</span>)</li> </ul><li>Some patients have a craving (pica) for ice.</li><li>Laboratory findings</li><ul> <li>(1) Decreased MCV</li><li>(2) Decreased serum iron, iron saturation
<blockquote style="color: blue; ">Iron deficiency: ↓ iron, % saturation, ferritin; ↑ TIBC, RDW</blockquote></li><li>(3) Decreased serum ferritin (<30 ng/mL)</li><li>(4) Increased TIBC, RDW</li><li>(5) Microcytic and normocytic cells with increased central area of pallor (<span>[[Fig. 11-11|Figure 11-11]]</span>)
<blockquote style="color: blue; ">Stages of iron deficiency: all lab studies abnormal <i>before</i> anemia is present</blockquote></li><li>(6) Increased serum free erythrocyte protoporphyrin (FEP)</li><ul> <li>Less iron combines with protoporphyrin.</li> </ul><li>(7) Thrombocytosis</li><ul> <li>(a) Common finding in chronic iron deficiency
<blockquote style="color: blue; ">Thrombocytosis: common finding in chronic iron deficiency</blockquote></li><li>(b) Reactive phenomenon to increase blood viscosity</li> </ul><li>(8) Leukocyte count is usually normal.</li><ul> <li>Eosinophilia occurs in hookworm infestations.</li> </ul> </ul> </ol><li>Treatment</li><ol type="a"> <li>Ferrous sulfate, given orally
<blockquote style="color: blue; ">Rx iron deficiency: ferrous sulfate</blockquote></li><li>Hct should increase 0.5% to 1%/day after the initial lag period.</li><li>Lack of response</li><ul> <li>(1) Noncompliance</li><li>(2) Continued blood loss</li><li>(3) Iron is not being reabsorbed.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC011018"></a> <br><a name="P011023"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">ACD: most common anemia in hospitalized patients</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common anemia in hospitalized patients</li><li>Common causes
<blockquote style="color: blue; ">ACD: most common anemia in malignancy, alcohol excess</blockquote></li><ul> <li>(1) Chronic inflammation</li><ul> <li>Examples-rheumatoid arthritis, tuberculosis</li> </ul><li>(2) Alcoholism</li><ul> <li>Most common overall anemia</li> </ul><li>(3) Malignancy</li><ul> <li>Most common overall anemia</li> </ul> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Decreased synthesis of heme (see <span>[[Fig. 11-9|Figure 11-9]]</span>)</li><li>Decrease renal production of EPO (some cases)</li><li>Liver synthesis and release of hepcidin
<blockquote style="color: blue; ">Hepcidin: antimicrobial peptide synthesized/released by liver</blockquote></li><ul> <li>(1) Antimicrobial peptide released by the liver in response to inflammation</li><ul> <li>Acute phase reactant (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>)</li> </ul><li>(2) Enters macrophages in the bone marrow</li><ul> <li>Prevents the release of iron to transferrin
<blockquote style="color: blue; ">Hepcidin: ↑ macrophage iron stores; "reticuloendothelial cell block"</blockquote></li> </ul><li>(3) Ferritin synthesis and iron stores increase in bone marrow macrophages.</li><ul> <li>Iron comes into the macrophage but only a little goes out.</li> </ul> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Decreased MCV</li><li>Decreased serum iron, TIBC, iron saturation
<blockquote style="color: blue; ">ACD: ↓ iron, TIBC, % saturation; ↑ ferritin</blockquote></li><li>Increased serum ferritin (>100 ng/mL)</li><li>Increased serum FEP</li><ul> <li>Less iron combines with protoporphyrin.</li> </ul><li>Anemia rarely <9 g/dL.</li> </ol><li>Treatment</li><ol type="a"> <li>Treat the underlying disease causing the inflammation.</li><li>In some cases, giving EPO increases the Hb concentration.</li> </ol> </ol>
</div></html>
<html><a name="HC011019"></a> <br><a name="PB011006"></a><div class="BB" style="color: rgb(47, 79, 79); ">Hb electrophoresis is normal, because all Hb types require α-globin chains. The Hb concentration is decreased; however, the relative proportions of the normal Hbs remains the same (see <span>[[Fig. 11-8B|Figure 11-8]]</span>).α-Thal trait: ↓ HbA, HbA<sub>2</sub>, HbF (normal electrophoresis); RBC count</div><a name="PB011007"></a><div class="BB" style="color: rgb(47, 79, 79); ">Normal β-globin chain synthesis is designated β; some β-globin chain synthesis is designated β<sup>+</sup>; absence of β-globin chain synthesis is designated β<sup>0</sup>.</div><a name="P011024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal recessive disorders
<blockquote style="color: blue; ">Blacks: can have α- or β-thalassemia</blockquote></li><li>α-Thal is common in Southeast Asians and in blacks.</li><li>β-Thal is common in blacks, Greeks, and Italians.</li> </ol><li>Pathogenesis of α-thal</li><ol type="a"> <li>Decrease in α-globin chain synthesis due to gene deletions (see <span>[[Fig. 11-9|Figure 11-9]]</span>)
<blockquote style="color: blue; ">α-Thal: due to gene deletions</blockquote></li><ul> <li>Four genes control α-globin chain synthesis.</li> </ul><li>One gene deletion produces a silent carrier.</li><ul> <li><i>Not</i> associated with anemia</li> </ul><li>The combination of two gene deletions is called α-thal trait (<span>[[Fig. 11-12|Figure 11-12]]</span>).
<blockquote style="color: blue; ">α-Thal trait: two gene deletions</blockquote></li><ul> <li>(1) Mild anemia with an increased RBC count</li><li>(2) In blacks</li><ul> <li>Associated with a loss of one gene on <i>each</i> chromosome (α/- α/-)</li> </ul><li>(3) In Asians</li><ul> <li>(a) Associated with a loss of both genes on the <i>same</i> chromosome (-/- α/α)</li><li>(b) Increased risk for developing more severe types of α-thal</li> </ul><li>(4) Decreased MCV, Hb, and Hct</li><li>(5) Increased RBC count</li><li>(6) Normal RDW, serum ferritin, serum FEP, Hb electrophoresis</li><li>(7) Tear drop RBCs in peripheral blood.
<blockquote style="color: blue; ">α-Thal trait: ↓ HbA, HbA<sub>2</sub>, HbF (normal electrophoresis); ↑ RBC count</blockquote></li><ul> <li>Damage to RBC membrane from removal of excess globin chains</li> </ul><li>(8) There is no treatment.</li><ul> <li>Do <i>not</i> treat with iron; danger of iron overload.</li> </ul> </ul><li>The combination of three gene deletions is called HbH (four β-chains) disease.
<blockquote style="color: blue; ">HbH: four β-chains</blockquote></li><ul> <li>(1) Severe hemolytic anemia</li><ul> <li>Excess β-chain inclusions cause macrophage destruction of the RBCs (hemolytic anemia).</li> </ul><li>(2) Hb electrophoresis detects HbH.</li> </ul><li>The combination of four gene deletions is called Hb Bart (four γ-chains) disease.
<blockquote style="color: blue; ">Hb Bart: four γ-chains</blockquote></li><ul> <li>(1) Incompatible with life</li><li>(2) Hb electrophoresis shows an increase in Hb Bart.</li> </ul> </ol><li>Pathogenesis of β-thal</li><ol type="a"> <li>Decrease in β-globin chain synthesis (see <span>[[Fig. 11-9|Figure 11-9]]</span>)</li><ul> <li>(1) Mild anemia is most often due to DNA splicing defects.
<blockquote style="color: blue; ">β-Thal: mild-DNA splicing defect; severe-stop codon</blockquote></li><li>(2) Severe anemia is due to a nonsense mutation with formation of a stop codon.</li><ul> <li>Premature termination of β-globin chain synthesis or absent β-globin chain synthesis.</li> </ul> </ul><li>Normal synthesis of α-, δ-, γ-globin chains</li><li>β-Thal minor (β/β<sup>+</sup>)
<blockquote style="color: blue; ">β-Thal minor: β/β<sup>+</sup></blockquote></li><ul> <li>(1) Mild microcytic anemia</li><li>(2) Mild protective effect against falciparum malaria</li><ul> <li>RBC life span is shorter than normal.</li> </ul><li>(3) Decreased MCV, Hb, and Hct</li><li>(4) Increased RBC count</li><li>(5) Normal RDW, serum ferritin, FEP</li><ul> <li>Serum FEP is normal because heme synthesis is normal.</li> </ul><li>(6) Hb electrophoresis (see <span>[[Fig. 11-8C|Figure 11-8]]</span>)</li><ul> <li>(a) Decreased HbA (2α/2β)
<blockquote style="color: blue; ">β-Thal minor: ↓HbA; ↑ RBC count, HbA<sub>2</sub>, HbF</blockquote></li><li>(b) Increased HbA<sub>2</sub> (2α/2δ) and HbF (2α/2γ)</li> </ul><li>(7) There is no treatment.</li><ul> <li>Do <i>not</i> treat with iron; danger of iron overload.</li> </ul> </ul><li>β-Thal major (Cooley's anemia; β<sup>0</sup>/β<sup>0</sup>)</li><ul> <li>(1) Severe hemolytic anemia
<blockquote style="color: blue; ">β-Thal major: β<sup>0</sup>/β<sup>0</sup></blockquote></li><ul> <li>(a) RBCs with α-chain inclusions are removed by macrophages in the spleen.</li><ul> <li>Causes an increase in unconjugated bilirubin (jaundice)</li><li>(b) RBCs with α-chain inclusions undergo apoptosis in the bone marrow (ineffective erythropoiesis).</li> </ul><li>(2) Extramedullary hematopoiesis</li><li>(3) Increased RDW and reticulocytes</li><li>(4) Hb electrophoresis (see <span>[[Fig. 11-8D|Figure 11-8]]</span>)</li><ul> <li>(a) <i>No</i> synthesis of HbA</li><li>(b) Increase in HbA<sub>2</sub> and HbF
<blockquote style="color: blue; ">β-Thal major: no HbA; ↑ HbA<sub>2</sub>, HbF</blockquote></li> </ul><li>(5) Long-term transfusion requirement</li><ul> <li>Danger of iron overload (called hemosiderosis)</li> </ul> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC011020"></a> <br><a name="PB011008"></a><div class="BB" style="color: rgb(47, 79, 79); ">Tubular damage by lead produces Fanconi syndrome. The syndrome includes proximal renal tubular acidosis (loss of bicarbonate in urine), aminoaciduria, phosphaturia, and glucosuria.</div><a name="P011025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Chronic alcoholism (most common cause)</li><li>Pyridoxine (vitamin B<sub>6</sub>) deficiency</li><li>Lead (Pb) poisoning</li><li>Hereditary types</li><ul> <li>X-linked recessive inheritance</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Defect in heme synthesis within the mitochondria (see <span>[[Fig. 11-9|Figure 11-9]]</span>)</li><ul> <li>(1) Heme is the end-product of porphyrin synthesis.</li><li>(2) Heme has a negative feedback relationship with δ-aminolevulinic acid synthase.</li><ul> <li>δ-Aminolevulinic acid synthase is the rate-limiting enzyme of heme synthesis.
<blockquote style="color: blue; ">Sideroblastic anemia: defect in heme synthesis in the mitochondria; ringed sideroblasts</blockquote></li> </ul> </ul><li>Iron accumulates in the mitochondria forming ringed sideroblasts (<span>[[Fig. 11-13|Figure 11-13]]</span>).</li><li>Iron-overload type of anemia</li><ul> <li>(1) Increase in iron stores in the bone marrow macrophages</li><li>(2) Sideroblasts die in the marrow, and iron is added to the macrophages.</li> </ul> </ol><li>Chronic alcoholism</li><ol type="a"> <li>Alcohol is a mitochondrial toxin.
<blockquote style="color: blue; ">Sideroblastic anemia: alcohol most common cause</blockquote></li><ul> <li>Damages heme biosynthetic pathways in the mitochondria</li> </ul><li>Sideroblastic anemia occurs in ∼30% of hospitalized chronic alcoholics.</li> </ol><li>Pyridoxine deficiency</li><ol type="a"> <li>Vitamin B<sub>6</sub> is a cofactor for δ-aminolevulinic acid synthase.</li><ul> <li>Rate-limiting reaction of heme synthesis (see <span>[[Fig. 11-9|Figure 11-9]]</span>)</li> </ul><li>Most common cause of deficiency is isoniazid (INH) therapy.</li><ul> <li>(1) INH is used in the treatment of tuberculosis.
<blockquote style="color: blue; ">Pyridoxine deficiency: INH most common cause</blockquote></li><li>(2) INH complexes with pyridoxine.</li> </ul> </ol><li>Lead (Pb) poisoning</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Most common in children ages 1 to 5 years old</li><li>(2) Causes</li><ul> <li>(a) Pica (abnormal craving) for eating lead-based paint</li><ul> <li>Common cause of childhood lead poisoning in inner cities</li> </ul><li>(b) Pottery glazes commercial and homemade
<blockquote style="color: blue; ">Pb poisoning: paint, batteries</blockquote></li> </ul><li>(3) Working in a battery or ammunition factory</li><li>(4) Radiator repair mechanics</li><li>(5) Air contamination from smelter</li> </ul><li>Pb denatures enzymes
<blockquote style="color: blue; ">Pb: denatures ferrochelatase, ALA dehydrase, ribonuclease</blockquote></li><ul> <li>(1) Ferrochelatase (heme synthase)</li><ul> <li>(a) Iron cannot bind with protoporphyrin to form heme.</li><li>(b) Increase in serum FEP, which is proximal to the enzyme block</li> </ul><li>(2) Aminolevulinic acid (ALA) dehydrase</li><ul> <li>Causes an increase in δ-ALA, which is proximal to the enzyme block</li> </ul><li>(3) Ribonuclease</li><ul> <li>(a) Ribosomes cannot be degraded and persist in the RBC.
<blockquote style="color: blue; ">Pb poisoning: coarse basophilic stippling</blockquote></li><li>(b) Produces coarse basophilic stippling (<span>[[Fig. 11-14|Figure 11-14]]</span>)</li> </ul> </ul><li>Clinical and laboratory findings</li><ul> <li>(1) Abdominal colic with diarrhea</li><ul> <li>(a) Pb is visible in the gastrointestinal tract on plain abdominal radiographs (<span>[[Fig. 11-15|Figure 11-15]]</span>).</li><li>(b) Usually occurs in children</li> </ul><li>(2) Encephalopathy in children</li><ul> <li>(a) δ-ALA damages neurons, increases vessel permeability (cerebral edema), and causes demyelination.</li><li>(b) Learning disabilities in children</li> </ul><li>(3) Growth retardation in children</li><ul> <li>(a) Pb deposits in the epiphysis of growing bone (<span>[[Fig. 11-16|Figure 11-16]]</span>).
<blockquote style="color: blue; ">Pb poisoning: Pb deposits in epiphyses</blockquote></li><li>(b) Radiographs show increased density in the epiphyses.</li> </ul><li>(4) Peripheral neuropathy in adults</li><ul> <li>Examples-foot drop (peroneal nerve palsy), wrist drop (radial nerve palsy), claw hand (ulnar nerve palsy)</li> </ul><li>(5) Nephrotoxic damage to proximal renal tubules</li><li>(6) Pb line in the gums</li><ul> <li>Usually in adults with Pb poisoning and gingivitis</li> </ul><li>(7) Increased whole blood and urine Pb levels</li><ul> <li>Best screen and confirmatory test for Pb poisoning</li> </ul> </ul><li>Treatment
<blockquote style="color: blue; ">Rx Pb poisoning: chelation therapy</blockquote></li><ul> <li>Chelation therapy-succimer, dimercaprol, EDTA (ethylenediaminetetra-acetic acid)</li> </ul> </ol><li>Laboratory findings in sideroblastic anemias
<blockquote style="color: blue; ">Sideroblastic anemia: ↑ serum iron, iron saturation, ferritin; ↓ MCV, TIBC</blockquote></li><ol type="a"> <li>Increased serum iron, iron saturation, and ferritin</li><li>Decreased MCV and TIBC</li><li>Ringed sideroblasts are present in a bone marrow aspirate.</li> </ol><li>Summary table of microcytic anemias (<span>[[Table 11-2|Table 11-2. LABORATORY FINDINGS IN MICROCYTIC ANEMIAS]]</span>)</li> </ol>
</div></html>
![[11.III.A.Types of microcytic anemias]]
<<tiddler [[11.III.A.Types of microcytic anemias]]>>
![[11.III.B.Pathogenesis (Fig. 11-9)]]
<<tiddler [[11.III.B.Pathogenesis (Fig. 11-9)]]>>
![[11.III.C.Iron deficiency anemia]]
<<tiddler [[11.III.C.Iron deficiency anemia]]>>
![[11.III.D.Anemia of chronic disease (ACD)]]
<<tiddler [[11.III.D.Anemia of chronic disease (ACD)]]>>
![[11.III.E.Thalassemia (thal; α and β)]]
<<tiddler [[11.III.E.Thalassemia (thal; α and β)]]>>
![[11.III.F.Sideroblastic anemia]]
<<tiddler [[11.III.F.Sideroblastic anemia]]>>
<html><a name="HC011022"></a> <br><a name="P011036"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Vitamin B<sub>12</sub>: only present in animal products</blockquote>
<ol type="1"> <li>Present in meat, eggs, and dairy products</li><li>Parietal cells synthesize intrinsic factor (IF) and hydrochloric acid (HCl).</li><li>Gastric acid converts pepsinogen to pepsin.
<blockquote style="color: blue; ">Parietal cells: synthesize IF and HCl</blockquote></li><ul> <li>Pepsin frees vitamin B<sub>12</sub> from ingested proteins.</li> </ul><li>Free vitamin B<sub>12</sub> is bound to R-binders synthesized in the salivary glands.</li><li>Pancreatic enzymes in the duodenum cleave off the R-binders.</li><ul> <li>Vitamin B<sub>12</sub> binds to IF to form a complex.</li> </ul><li>Vitamin B<sub>12</sub>-IF complex is reabsorbed in the terminal ileum.
<blockquote style="color: blue; ">Vitamin B<sub>12</sub>: reabsorbed in terminal ileum</blockquote></li><li>Vitamin B<sub>12</sub> binds to transcobalamin II and is secreted into plasma.</li><ul> <li>Delivered to metabolically active cells or stored in the liver (6-9 years)</li> </ul> </ol>
</div></html>
<html><a name="HC011023"></a><span>[[Table 11-3|Table 11-3. CAUSES OF VITAMIN B]]</span> <br> <br><a name="P011037"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Vitamin B<sub>12</sub> deficiency: pernicious anemia most common cause</blockquote>
</div></html>
<html><a name="HC011024"></a> <br><a name="P011038"></a><div class="PA" style="color: black; "><ol type="1"> <li>Present in green vegetables and animal proteins</li><ul> <li>In the form of polyglutamates</li> </ul><li>Converted to monoglutamates by intestinal conjugase</li><ul> <li>Intestinal conjugase is inhibited by phenytoin.
<blockquote style="color: blue; ">Intestinal conjugase: inhibited by phenytoin</blockquote></li> </ul><li>Monoglutamates are reabsorbed in the jejunum.
<blockquote style="color: blue; ">Monoglutamate reabsorption: inhibited by alcohol and oral contraceptives</blockquote></li><ol type="a"> <li>Converted to methyltetrahydrofolate, the circulating form of folate</li><li>Reabsorption is blocked by alcohol and oral contraceptives.</li><li>There is only a 3- to 4-month supply of folate in the liver.</li> </ol> </ol>
</div></html>
<html><a name="HC011025"></a><span>[[Table 11-4|Table 11-4. CAUSES OF FOLATE DEFICIENCY]]</span> <br> <br> </html>
<html><a name="HC011026"></a> <br><a name="P011039"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Folate deficiency: alcohol most common cause</blockquote>
<ol type="1"> <li>Impaired DNA synthesis</li><ol type="a"> <li>Delayed nuclear maturation</li><ul> <li>(1) Causes a block in cell division leading to large, nucleated hematopoietic cells</li><li>(2) Enlarged cells are called megaloblasts (<span>[[Fig. 11-17|Figure 11-17]]</span>).
<blockquote style="color: blue; ">Vitamin B<sub>12</sub>/folate deficiency: delayed nuclear maturation; megaloblasts</blockquote></li> </ul><li>Affects all rapidly dividing cells</li><ul> <li>Examples-RBCs, leukocytes, platelets, intestinal epithelium</li> </ul><li>Cellular RNA and protein synthesis continue unabated.</li><ul> <li>Cytoplasmic volume continues to expand.</li> </ul> </ol><li>Ineffective erythropoiesis</li><ol type="a"> <li>Megaloblastic precursors outside the bone marrow sinusoids are phagocytosed by macrophages.</li><li>Megaloblastic precursors undergo apoptosis causing pancytopenia.</li><ul> <li>Anemia, neutropenia, and thrombocytopenia</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC011027"></a><span>[[Fig. 11-18|Figure 11-18]]</span> <br> <br><a name="PB011009"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Folate deficiency</b> is the most common cause of increased serum homocysteine levels in the United States. Homocysteine damages endothelial cells leading to vessel thrombosis.</div><a name="P011040"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Vitamin B<sub>12</sub>/folate deficiency: pancytopenia; apoptosis, macrophage phagocytosis</blockquote>
<ol type="1"> <li>Vitamin B<sub>12</sub> removes the methyl group from methyltetrahydrofolate (N<sup>5</sup>-methyl-FH<sub>4</sub>).</li><ol type="a"> <li>Produces tetrahydrofolate (FH<sub>4</sub>)</li><li>Methyl-vitamin B<sub>12</sub> transfers the methyl group to homocysteine to produce methionine.</li><ul> <li>Deficiency of vitamin B<sub>12</sub> traps N<sup>5</sup>-methyl-FH<sub>4</sub> in its circulating form; may falsely increase the serum folate in 30% of cases.
<blockquote style="color: blue; ">↑ Homocysteine: folate (most common) and vitamin B<sub>12</sub> deficiency</blockquote></li> </ul><li>Deficiency of folate or vitamin B<sub>12</sub> increases plasma homocysteine.</li> </ol><li>Thymidylate synthase converts deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP).</li><ul> <li>Thymidylate synthase is irreversibly inhibited by 5-fluorouracil.
<blockquote style="color: blue; ">Thymidylate synthase: irreversibly inhibited by 5-fluorouracil</blockquote></li> </ul><li>Dihydrofolate reductase converts dihydrofolate (FH<sub>2</sub>) to FH<sub>4</sub>.</li><ul> <li>Dihydrofolate reductase is inhibited by methotrexate and trimethoprim.</li> </ul> </ol>
</div></html>
<html><a name="HC011028"></a><span>[[Fig. 11-19|Figure 11-19]]</span> <br> <br><a name="P011041"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Dihydrofolate reductase: inhibited by methotrexate (reversible), trimethoprim</blockquote>
<ol type="1"> <li>Propionyl CoA is converted to methylmalonyl CoA.</li><li>Methylmalonyl CoA is converted to succinyl CoA.</li><ul> <li>Vitamin B<sub>12</sub> is a cofactor for methylmalonyl CoA mutase.
<blockquote style="color: blue; ">Vitamin B<sub>12</sub>: odd chain fatty acid metabolism</blockquote></li> </ul><li>Vitamin B<sub>12</sub> deficiency causes an increase in propionyl and methylmalonyl CoA and their corresponding acids.</li><ul> <li>Propionyl CoA replaces acetyl CoA in neuronal membranes resulting in demyelination.</li> </ul> </ol>
</div></html>
<html><a name="HC011029"></a> <br><a name="P011042"></a><div class="PA" style="color: black; "><ol type="1"> <li>Findings in pernicious anemia (PA)
<blockquote style="color: blue; ">PA: ↑ incidence blood group A</blockquote></li><ol type="a"> <li>Increased incidence in blood group A individuals</li><li>Achlorhydria (lack of gastric acid) due to destruction of parietal cells</li><ul> <li>(1) Maldigestion of food</li><li>(2) Hypergastrinemia</li><ul> <li>Due to loss of acid inhibition of gastrin</li> </ul> </ul><li>Antibodies associated with pernicious anemia (type II hypersensitivity)</li><ul> <li>(1) Antibodies directed against the proton pump in parietal cells (85-90% of cases)</li><li>(2) Antibodies that block binding of vitamin B<sub>12</sub> to IF (60-75% of cases)
<blockquote style="color: blue; ">PA: ↑ incidence blood group A</blockquote></li><ul> <li>Most specific test for pernicious anemia</li> </ul><li>(3) Antibodies that prevent binding of vitamin B<sub>12</sub>-IF complexes to ileal receptors (30-50% of cases)
<blockquote style="color: blue; ">PA: type II hypersensitivity</blockquote></li> </ul><li>Antibody destruction of parietal cells causes chronic atrophic gastritis of the body and fundus.
<blockquote style="color: blue; ">PA: ↑ antibodies, gastrin levels</blockquote></li><ul> <li>Increased incidence of gastric adenocarcinoma</li> </ul> </ol><li>Smooth, sore tongue with atrophy of papillae</li><li>Neurologic disease</li><ol type="a"> <li>Peripheral neuropathy with sensorimotor dysfunction</li><li>Subacute combined degeneration (demyelination) of the spinal cord (<span>[[Fig. 11-20|Figure 11-20]]</span>)</li><ul> <li>(1) Posterior column dysfunction
<blockquote style="color: blue; ">Vitamin B<sub>12</sub> deficiency: posterior columns, lateral corticospinal tract, dorsal spinocerebellar tract</blockquote></li><ul> <li>Decrease in vibratory sensation and proprioception (joint sense)</li> </ul><li>(2) Lateral corticospinal tract dysfunction with spasticity</li> </ul><li>Dorsal spinocerebellar tract demyelination</li><ul> <li>Produces ataxia</li> </ul><li>Dementia
<blockquote style="color: blue; ">Macrocytic anemia neurologic disease: vitamin B<sub>12</sub> deficiency</blockquote></li><li>Possible to have neurologic disease without anemia</li> </ol> </ol>
</div></html>
<html><a name="HC011030"></a> <br><a name="PB011010"></a><div class="BB" style="color: rgb(47, 79, 79); ">The <b>Schilling test</b> has been used in the past to demonstrate impairment of reabsorption of vitamin B<sub>12</sub>. This is achieved indirectly by combining orally administered radioactive vitamin B<sub>12</sub> with IF, or with pancreatic extract, or alone after pretreatment with antibiotics followed by a 24-hour urine collection to measure radioactive vitamin B<sub>12</sub>. Lack of reabsorption of radioactive vitamin B<sub>12</sub> excludes a potential cause of impaired reabsorption, while the presence of reabsorption confirms the cause of the impaired reabsorption. For example, if the combination of radioactive vitamin B<sub>12</sub> + IF leads to an increase in radioactive vitamin B<sub>12</sub> in the urine, the patient has pernicious anemia; if it does not, the diagnosis of pernicious anemia is excluded. Similarly, correction with pancreatic extract implicates chronic pancreatitis as the cause or bacterial overgrowth as the cause, if antibiotics correct the reabsorption.</div><a name="P011043"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">↑ Methylmalonic acid: most sensitive test for vitamin B<sub>12</sub> deficiency</blockquote>
<ol type="1"> <li>Decreased serum vitamin B<sub>12</sub></li><li>Increased serum homocysteine and methylmalonic acid (95% of cases)</li><li>Peripheral blood findings</li><ol type="a"> <li>Pancytopenia</li><li>Oval macrocytes</li><li>Hypersegmented neutrophils (<span>[[Fig. 11-21|Figure 11-21]]</span>)
<blockquote style="color: blue; ">Hypersegmented neutrophil: marker for folate or vitamin B<sub>12</sub> deficiency</blockquote></li><ul> <li>More than five nuclear lobes</li> </ul> </ol><li>Bone marrow findings</li><ul> <li>Megaloblastic nucleated cells with primitive open (lacy) chromatin pattern</li> </ul><li>Schilling test localizes some of the causes of vitamin B<sub>12</sub> deficiency.</li><ul> <li>Although it is <i>not</i> routinely performed anymore, it is a good review of causes of vitamin B<sub>12</sub> deficiency.
<blockquote style="color: blue; ">Schilling test: defines the cause of vitamin B<sub>12</sub> deficiency</blockquote></li> </ul> </ol>
</div></html>
<html><a name="HC011031"></a> <br><a name="P011044"></a><div class="PA" style="color: black; "><ol type="1"> <li>Similar to vitamin B<sub>12</sub> deficiency with the <i>exception</i> of neurologic disease</li><li>Increased risk for open neural tube defects in the fetus
<blockquote style="color: blue; ">↓ Maternal intake of folate: increased risk for open neural tube defect in newborn</blockquote></li><ul> <li>Due to decreased maternal intake of folate <i>prior</i> to conception</li> </ul> </ol>
</div></html>
<html><a name="HC011032"></a> <br><a name="P011045"></a><div class="PA" style="color: black; "><ol type="1"> <li>Peripheral blood and bone marrow findings are similar to vitamin B<sub>12</sub> deficiency.</li><li>Decreased serum folate and RBC folate (best screening test)
<blockquote style="color: blue; ">RBC folate: best indicator of folate stores</blockquote></li> </ol>
</div></html>
<html><a name="HC011033"></a> <br><a name="PB011011"></a><div class="BB" style="color: rgb(47, 79, 79); ">It is important to distinguish folate from vitamin B<sub>12</sub> deficiency. Pharmacologic doses of folate will correct the hematologic findings in both folate and vitamin B<sub>12</sub> deficiency; however, neurologic disease is <i>not</i> corrected.</div><a name="P011046"></a><div class="PA" style="color: black; "><ol type="1"> <li>Treatment of vitamin B<sub>12</sub> deficiency</li><ol type="a"> <li>Intramuscular injection of vitamin B<sub>12</sub></li><li>Treatment is indefinite in pernicious anemia.</li> </ol><li>Treatment of folate deficiency</li><ul> <li>Oral administration of monoglutamic folic acid</li> </ul> </ol>
</div></html>
<html><a name="HC011034"></a><span>[[Table 11-5|Table 11-5. CLINICAL AND LABORATORY FINDINGS IN VITAMIN B]]</span> <br> <br> </html>
![[11.IV.A.Vitamin B12 metabolism]]
<<tiddler [[11.IV.A.Vitamin B12 metabolism]]>>
![[11.IV.B.Causes of vitamin B12 deficiency (Table 11-3)]]
<<tiddler [[11.IV.B.Causes of vitamin B12 deficiency (Table 11-3)]]>>
![[11.IV.C.Folate metabolism]]
<<tiddler [[11.IV.C.Folate metabolism]]>>
![[11.IV.D.Causes of folate deficiency (Table 11-4)]]
<<tiddler [[11.IV.D.Causes of folate deficiency (Table 11-4)]]>>
![[11.IV.E.Pathogenesis of macrocytic anemia in folate and vitamin B12 deficiency]]
<<tiddler [[11.IV.E.Pathogenesis of macrocytic anemia in folate and vitamin B12 deficiency]]>>
![[11.IV.F.Vitamin B12 and folate in DNA synthesis (Fig. 11-18)]]
<<tiddler [[11.IV.F.Vitamin B12 and folate in DNA synthesis (Fig. 11-18)]]>>
![[11.IV.G.Vitamin B12 in odd-chain fatty acid metabolism (Fig. 11-19)]]
<<tiddler [[11.IV.G.Vitamin B12 in odd-chain fatty acid metabolism (Fig. 11-19)]]>>
![[11.IV.H.Clinical findings in vitamin B12 deficiency]]
<<tiddler [[11.IV.H.Clinical findings in vitamin B12 deficiency]]>>
![[11.IV.I.Laboratory findings in vitamin B12 deficiency]]
<<tiddler [[11.IV.I.Laboratory findings in vitamin B12 deficiency]]>>
![[11.IV.J.Clinical findings in folate deficiency]]
<<tiddler [[11.IV.J.Clinical findings in folate deficiency]]>>
![[11.IV.K.Laboratory findings in folate deficiency]]
<<tiddler [[11.IV.K.Laboratory findings in folate deficiency]]>>
![[11.IV.L.Treatment of vitamin B12 and folate deficiency]]
<<tiddler [[11.IV.L.Treatment of vitamin B12 and folate deficiency]]>>
![[11.IV.M.Comparison table of vitamin B12 and folate deficiency (Table 11-5)]]
<<tiddler [[11.IV.M.Comparison table of vitamin B12 and folate deficiency (Table 11-5)]]>>
![[11.IV.N.Nonmegaloblastic macrocytosis]]
<<tiddler [[11.IV.N.Nonmegaloblastic macrocytosis]]>>
<html><a name="HC011035"></a> <br><a name="P011047"></a><div class="PA" style="color: black; "><ol type="1"> <li>General differences from megaloblastic macrocytic anemias</li><ol type="a"> <li>Macrocytes are round rather than oval</li><li>Hypersegmented neutrophils are <i>not</i> present.</li><li>Leukocytes and platelets are quantitatively normal.</li><li>Absence of glossitis and neuropathy</li><li>Anemia may <i>not</i> be present.</li><li>Alcohol excess is the most common cause for all types of the macrocytosis.</li> </ol><li>Liver disease associated with alcohol</li><ol type="a"> <li>MCV ranges from 105 ± 10 μm<sup>3</sup>.
<blockquote style="color: blue; ">Alcohol liver disease: round macrocytic target cells</blockquote></li><li>Thin, round, macrocytic target cells (<span>[[Fig. 11-22|Figure 11-22]]</span>)</li><ul> <li>Excess RBC membrane due to increased membrane cholesterol</li> </ul><li>Life span of the RBCs is <i>not</i> decreased; there is no anemia.</li> </ol><li>Direct toxic effect of alcohol</li><ol type="a"> <li>MCV ranges from 100 to 110 μm<sup>3</sup>.</li><li>Vacuolization of RBC precursors in bone marrow</li><li>Abstinence from alcohol reverses the macrocytosis and anemia.</li> </ol> </ol>
</div></html>
<html><a name="HC011037"></a> <br><a name="P011054"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Acute blood loss: external, internal</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>External blood loss</li><ul> <li>Examples-open fractures, knife wound</li> </ul><li>Internal blood loss</li><ul> <li>Examples-ruptured abdominal aortic aneurysm; ruptured spleen</li> </ul><li>Most common cause of hypovolemic shock</li> </ol><li>Clinical and laboratory findings (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)
<blockquote style="color: blue; ">Signs volume depletion: ↓ blood pressure, ↑ pulse</blockquote></li><li>Requires 5 to 7 days <i>before</i> a reticulocyte response is observed</li> </ol>
</div></html>
<html><a name="HC011038"></a> <br><a name="P011055"></a><div class="PA" style="color: black; "><ol type="1"> <li>Anemia is normocytic <i>before</i> it becomes microcytic.</li><ul> <li>ACD is microcytic in only 10% to 30% of cases.</li> </ul><li>Serum ferritin is most useful in distinguishing the two anemias.
<blockquote style="color: blue; ">Aplastic anemia: most cases idiopathic; drugs most common known cause</blockquote></li> </ol>
</div></html>
<html><a name="HC011039"></a> <br><a name="P011056"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes (<span>[[Table 11-6|Table 11-6. CAUSES OF APLASTIC ANEMIA]]</span>)</li><li>Pathogenesis</li><ol type="a"> <li>Antigenic alteration of myeloid stem cells</li><ul> <li>Causes T-cell activation and release of cytokines that suppress myeloid stem cells</li> </ul><li>Defective or deficient myeloid stem cells (acquired or hereditary)</li> </ol><li>Clinical findings</li><ol type="a"> <li>Fever due to infection associated with neutropenia</li><li>Bleeding due to thrombocytopenia
<blockquote style="color: blue; ">Aplastic anemia: fever, bleeding, fatigue</blockquote></li><li>Fatigue due to anemia</li> </ol><li>Laboratory findings</li><ol type="a"> <li>Pancytopenia
<blockquote style="color: blue; ">Aplastic anemia: pancytopenia</blockquote></li><li>Reticulocytopenia</li><li>Hypocellular bone marrow (<span>[[Fig. 11-23|Figure 11-23]]</span>)</li> </ol><li>Complete recovery occurs in < 10% of cases.</li><li>Treatment</li><ol type="a"> <li>Discontinue drug, if it is responsible</li><li>Broad-spectrum antibiotics to prevent infection</li><li>Transfusions with irradiated blood (if not a bone marrow transplant candidate)</li><ul> <li>Prevents graft-versus-host reaction (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>)</li> </ul><li>Immunosuppressive therapy</li><ul> <li>Examples-antilymphocyte globulin, cyclophosphamide, cyclosporin</li> </ul><li>Bone marrow transplantation</li><ul> <li>Good prognosis if patient is young and a compatible donor is found</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC011040"></a> <br><a name="P011057"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ul> <li>Decreased synthesis of EPO (most common cause)
<blockquote style="color: blue; ">Anemia CRF: ↓ EPO most common cause</blockquote></li> </ul><li>Laboratory findings</li><ol type="a"> <li>Normocytic anemia</li><li>Presence of burr cells (i.e., RBCs with an undulating membrane)</li><li>Platelet dysfunction
<blockquote style="color: blue; ">CRF: platelet dysfunction</blockquote></li><ul> <li>(1) Thrombocytopenia</li><li>(2) Defect in platelet aggregation that is reversible with dialysis</li><ul> <li>Prolonged bleeding time</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC011041"></a> <br><a name="P011058"></a><div class="PA" style="color: black; "><ol type="1"> <li>ACD most common anemia</li><li>Gastrointestinal bleeding (e.g., colorectal cancer)</li><ul> <li>Could be normocytic or microcytic</li> </ul><li>Metastasis to bone marrow</li><ol type="a"> <li>Malignant cells displace normal marrow hematopoietic cells into peripheral blood</li><ul> <li>Called myelophthisic anemia</li> </ul><li>Presence of nucleated RBCs and immature myeloid cells into the peripheral blood is called leukoerythroblastic smear (see <span>[[Fig. 12-1|Figure 12-1]]</span>).
<blockquote style="color: blue; ">Anemia malignancy: ACD, blood loss, metastasis to marrow, immunologic</blockquote></li> </ol><li>Immune hemolytic anemia (IHA)</li><ul> <li>Example-cold type IHA in chronic lymphocytic leukemia</li> </ul> </ol>
</div></html>
![[11.V.A.Acute blood loss]]
<<tiddler [[11.V.A.Acute blood loss]]>>
![[11.V.B.Early iron deficiency or ACD]]
<<tiddler [[11.V.B.Early iron deficiency or ACD]]>>
![[11.V.C.Aplastic anemia]]
<<tiddler [[11.V.C.Aplastic anemia]]>>
![[11.V.D.Chronic renal failure (CRF)]]
<<tiddler [[11.V.D.Chronic renal failure (CRF)]]>>
![[11.V.E.Malignancy]]
<<tiddler [[11.V.E.Malignancy]]>>
<html><a name="HC011043"></a> <br><a name="PB011012"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Haptoglobin</b> is an acute phase reactant that combines with Hb to form a complex that is phagocytosed and degraded by macrophages causing a decrease in serum haptoglobin. The amount of Hb in the complexes is so small that unconjugated bilirubin is <i>not</i> significantly increased enough to produce jaundice in most cases.</div><a name="P011060"></a><div class="PA" style="color: black; "><ol type="1"> <li>Intrinsic or extrinsic hemolytic anemias</li><ol type="a"> <li>Intrinsic refers to a defect in the RBC causing the anemia.
<blockquote style="color: blue; ">Types hemolytic anemia: intrinsic (defect in RBC), extrinsic (factors outside RBC)</blockquote></li><ul> <li>Examples-membrane defects, abnormal Hb, enzyme deficiency</li> </ul><li>Extrinsic refers to factors outside the RBC causing hemolysis.</li><ul> <li>Examples-stenotic aortic valve, immune destruction</li> </ul> </ol><li>Mechanisms of hemolysis (<span>[[Fig. 11-24|Figure 11-24]]</span>)</li><ol type="a"> <li>Extravascular hemolysis</li><ul> <li>(1) RBC phagocytosis by macrophages in the spleen (most common site) and liver</li><li>(2) Reasons for phagocytosis</li><ul> <li>(a) RBCs coated by IgG with or without C3b</li><li>(b) Abnormally shaped RBCs (e.g., spherocytes, sickle cells)
<blockquote style="color: blue; ">Extravascular hemolysis: macrophage phagocytosis; unconjugated hyperbilirubinemia</blockquote></li> </ul><li>(3) Increase in serum unconjugated bilirubin</li><ul> <li>End-product of macrophage degradation of Hb</li> </ul><li>(4) Increased serum lactate dehydrogenase (LDH) from hemolyzed RBCs</li> </ul><li>Intravascular hemolysis</li><ul> <li>(1) Hemolysis occurs within blood vessels.</li><li>(2) Causes of hemolysis</li><ul> <li>(a) Enzyme deficiency (e.g., deficiency of glucose-6-phosphate dehydrogenase)</li><li>(b) Complement destruction (e.g., IgM-mediated hemolysis)</li><li>(c) Mechanical damage (e.g., calcific aortic valve stenosis)</li> </ul><li>(3) Increased plasma and urine Hb</li><li>(4) Hemosiderinuria
<blockquote style="color: blue; ">Intravascular hemolysis: ↓ serum haptoglobin; hemoglobinuria</blockquote></li><ul> <li>Renal tubules convert iron in Hb into hemosiderin.</li> </ul><li>(5) Decreased serum haptoglobin</li><li>(6) Increased serum LDH from hemolyzed RBCs.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC011044"></a> <br><a name="P011061"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Autosomal dominant disorder
<blockquote style="color: blue; ">Hereditary spherocytosis: intrinsic defect, extravascular hemolysis</blockquote></li><li>Intrinsic defect with extravascular hemolysis</li><li>Membrane protein defect results in the loss of RBC membrane and spherocyte formation.</li><ul> <li>(1) Mutation in ankyrin is the most common defect.
<blockquote style="color: blue; ">Hereditary spherocytosis: mutation in ankyrin in cell membrane</blockquote></li><li>(2) Mutation in band 2, spectrin (α and β), or band 3 account for other defects.</li> </ul><li>Increased permeability of spherocytes to sodium</li><ul> <li>Due to membrane defect and dysfunctional Na<sup>+</sup>/K<sup>+</sup>-ATPase pump</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Jaundice due to increased unconjugated bilirubin
<blockquote style="color: blue; ">Hereditary spherocytosis: black, calcium bilirubinate gallstones</blockquote></li><li>Increased incidence of calcium bilirubinate gallstones</li><ul> <li>Due to increased concentration of conjugated bilirubin in bile</li> </ul><li>Splenomegaly</li><li>Aplastic crisis
<blockquote style="color: blue; ">Aplastic crisis: parvovirus induced</blockquote></li><ul> <li>May occur in children especially after a viral infection (e.g., parvovirus)</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Normocytic anemia with spherocytosis (<span>[[Fig. 11-25|Figure 11-25]]</span>)</li><ul> <li>Other causes of spherocytosis-warm immune hemolytic anemia, ABO hemolytic disease of newborn</li> </ul><li>Increased MCHC</li><li>Increased RBC osmotic fragility
<blockquote style="color: blue; ">Hereditary spherocytosis: ↑RBC osmotic fragility</blockquote></li><ul> <li>(1) Increased permeability of spherocytes to sodium and water</li><li>(2) Spherocytes rupture in mildly hypotonic salt solutions.</li> </ul> </ol><li>Treatment is splenectomy.</li><ul> <li>Spherocytes remain in the peripheral blood.</li> </ul> </ol>
</div></html>
<html><a name="HC011045"></a> <br><a name="P011062"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Autosomal dominant disorder</li><li>Defective spectrin and band 4.1</li> </ol><li>Clinical findings</li><ol type="a"> <li>Majority have no anemia or a mild hemolytic anemia.</li><li>Splenomegaly</li> </ol><li>Laboratory findings</li><ol type="a"> <li>Elliptocytes > 25% of RBCs in peripheral blood (<span>[[Fig. 11-26|Figure 11-26]]</span>)
<blockquote style="color: blue; ">Hereditary elliptocytosis: >25% elliptocytes in peripheral blood</blockquote></li><li>Increased osmotic fragility</li> </ol><li>Treatment is splenectomy in symptomatic patients.</li> </ol>
</div></html>
<html><a name="HC011046"></a> <br><a name="P011063"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Acquired membrane defect in myeloid stem cells
<blockquote style="color: blue; ">PNH: loss of anchor for DAF</blockquote></li><ul> <li>(1) Mutation causes loss of the anchor for decay accelerating factor (DAF).</li><li>(2) Normally DAF destabilizes C3 and C5 convertase adhering to RBCs, platelets, and neutrophils (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>).</li><ul> <li>Prevents activation of the membrane attack complex and subsequent lysis of RBCs, neutrophils, and platelets</li> </ul> </ul><li>Intravascular complement-mediated lysis of RBCs, neutrophils, and platelets</li><ul> <li>Occurs at night, because respiratory acidosis enhances complement attachment to these cells</li><li>PNH: intrinsic defect, intravascular hemolysis
<blockquote style="color: blue; ">PNF: intrinsic defect, intravascular hemolysis</blockquote></li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Episodic hemoglobinuria</li><ul> <li>May cause iron deficiency</li> </ul><li>Increased incidence of vessel thrombosis (e.g., hepatic vein)</li><ul> <li>Due to the release of aggregating agents from destroyed platelets</li> </ul><li>Increased risk for developing acute myelogenous leukemia</li> </ol><li>Peripheral blood findings</li><ol type="a"> <li>Normocytic anemia with pancytopenia
<blockquote style="color: blue; ">PNH: pancytopenia</blockquote></li><ul> <li>Microcytic if iron deficiency develops from hemoglobinuria</li> </ul><li>Decreased leukocyte alkaline phosphatase</li><li>Decreased serum haptoglobin</li><li>Increased serum/urine Hb</li> </ol><li>Diagnosis</li><ol type="a"> <li>Identify the defect on hematopoietic cells</li><ul> <li>Most sensitive test</li> </ul><li>Older tests
<blockquote style="color: blue; ">PNH: screen-sucrose hemolysis test; confirm-acidified serum test</blockquote></li><ul> <li>(1) Screening test is the sucrose hemolysis test (sugar water test).</li><ul> <li>Sucrose enhances complement destruction of RBCs.</li> </ul><li>(2) Confirmatory test is the acidified serum test (Ham test).</li><ul> <li>Acidified serum activates the alternative pathway causing hemolysis.</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC011047"></a> <br><a name="P011064"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal recessive disorder</li><li>Most common hemoglobinopathy in blacks</li><li>Heterozygote condition (sickle cell trait, HbAS) has no anemia.</li><ul> <li>Present in ∼10% of blacks</li> </ul><li>Homozygous condition (HbSS) produces anemia.
<blockquote style="color: blue; ">Trait × trait: 25% normal, 50% trait, 25% disease</blockquote></li><li>Pedigree with sickle cell trait persons</li><ul> <li>(1) Normal child 25%</li><li>(2) Sickle cell trait 50%</li><li>(3) Sickle cell disease 25%</li> </ul><li>Protective against <i>Plasmodium falciparum</i> malaria</li> </ol><li>Pathogenesis
<blockquote style="color: blue; ">Sickle cell anemia: intrinsic defect, extravascular hemolysis</blockquote></li><ol type="a"> <li>Predominantly extravascular hemolysis of sickle cells</li><li>Missense point mutation</li><ul> <li>Substitution of valine for glutamic acid at sixth position of β-globin chain
<blockquote style="color: blue; ">Sickle cell anemia: missense mutation; substitution of valine for glutamic acid</blockquote></li> </ul><li>Causes of sickling</li><ul> <li>(1) HbS molecules aggregate and polymerize into long needle-like fibers.</li><ul> <li>RBCs assume a sickle or boat-like shape (<span>[[Fig. 11-27|Figure 11-27]]</span>).</li> </ul><li>(2) Sickle Hb (HbS) concentration greater than 60% is the most important factor for sickling.</li><ul> <li>HbS concentration is too low in HbAS to produce sickling in the peripheral blood.</li> </ul><li>(3) Increase in deoxyhemoglobin (correlates with decreased O<sub>2</sub> saturation) increases the risk for sickling.</li><li>(a) Acidosis</li><ul> <li>Right-shifts the OBC causing O<sub>2</sub> release from RBCs</li><li>(b) Volume depletion</li> </ul><ul> <li>Intracellular dehydration causes an increase in concentration of deoxyhemoglobin</li> </ul><li>(c) Hypoxemia
<blockquote style="color: blue; ">Sickling: ↑ HbS, ↑ deoxyHb</blockquote></li><ul> <li>Decrease in arterial P<span style="font-variant:small-caps;">o</span><sub>2</sub> decreases O<sub>2</sub> saturation of Hb.</li> </ul> </ul><li>Reversible and irreversible sickling</li><ul> <li>(1) Initial sickling is reversible with administration of O<sub>2</sub>.</li><li>(2) Recurrent sickling causes irreversible sickling due to membrane damage.
<blockquote style="color: blue; ">Irreversible sickle cell: increased adherence to endothelial cells</blockquote></li><li>(3) Irreversibly sickled cells have increased adherence to endothelial cells in the microcirculation.</li><ul> <li>Microvascular occlusions (vaso-occlusive crises) produce ischemic damage.</li> </ul> </ul><li>HbF prevents sickling.
<blockquote style="color: blue; ">Sickling: HbF prevents sickling</blockquote></li><ul> <li>(1) Increased HbF at birth prevents sickling in HbSS for 5 to 6 months.</li><li>(2) Hydroxyurea increases the synthesis of HbF.
<blockquote style="color: blue; ">Hydroxyurea: ↑ HbF</blockquote></li> </ul><li>Key pathologic processes in HbSS</li><ul> <li>(1) Severe hemolytic anemia
<blockquote style="color: blue; ">Sickle cell anemia: severe hemolytic anemia; vaso-occlusive crises</blockquote></li><li>(2) Painful vaso-occlusive crises</li> </ul> </ol><li>Clinical findings in HbSS</li><ol type="a"> <li>Dactylitis (hand-foot syndrome)</li><ul> <li>(1) Painful swelling of hands and feet</li><ul> <li>Pain due to bone infarctions</li> </ul><li>(2) Occurs in infants (usually 6-9 months old)
<blockquote style="color: blue; ">Dactylitis: most common presentation in infants</blockquote></li> </ul><li>Acute chest syndrome</li><ul> <li>(1) Most common cause of death in adults</li><li>(2) Precipitated by</li><ul> <li>(a) Pneumonia</li><ul> <li><i>Streptococcus pneumoniae, Mycoplasma,</i> viruses</li> </ul><li>(b) Infarction</li><li>(c) Fat embolism</li> </ul><li>(3) Clinical findings</li><ul> <li>(a) Chest pain</li><li>(b) Wheezing</li><li>(c) Dyspnea</li> </ul><li>(4) Laboratory</li><ul> <li>Hypoxemia</li> </ul><li>(5) Chest x-ray reveals lung infiltrates.</li> </ul><li>Aseptic necrosis of the femoral head (see <span>[[Fig. 23-6|Figure 23-6]]</span>)
<blockquote style="color: blue; ">Acute chest syndrome: most common cause of death in adults</blockquote></li><li>Autosplenectomy</li><ul> <li>(1) Spleen is enlarged but dysfunctional by 2 years of age.</li><ul> <li>Nuclear remnants (Howell-Jolly bodies) appear in RBCs indicating loss of macrophage function (<span>[[Fig. 11-28|Figure 11-28]]</span>).
<blockquote style="color: blue; ">Howell-Jolly bodies: sign of splenic dysfunction</blockquote></li> </ul><li>(2) Spleen is fibrosed and diminished in size in young adults.</li> </ul><li>Increased susceptibility to infections</li><ul> <li>(1) Due to dysfunctional spleen</li><ul> <li>Impaired opsonization of encapsulated bacteria</li> </ul><li>(2) Children are at risk for <i>Streptococcus pneumoniae</i> sepsis.
<blockquote style="color: blue; ">Pathogens: <i>Streptococcus pneumoniae</i> sepsis, <i>Salmonella paratyphi</i> osteomyelitis</blockquote></li><ul> <li>(a) Most common cause of death in children</li><li>(b) Prophylactic penicillin recommended</li> </ul><li>(3) Increased incidence of osteomyelitis</li><ul> <li>Most often due to <i>Salmonella paratyphi</i>; less frequently to <i>Staphylococcus aureus</i></li> </ul> </ul><li>Aplastic crisis</li><ul> <li>(1) Reticulocytopenia</li><li>(2) Association with parvovirus</li> </ul><li>Sequestration crisis
<blockquote style="color: blue; ">Sequestration vs. aplastic crisis: reticulocytosis, reticulocytopenia, respectively</blockquote></li><ul> <li>(1) Rapid splenic enlargement</li><ul> <li>Entrapment of RBCs causing hypovolemia</li> </ul><li>(2) Reticulocytosis</li> </ul><li>Increased risk for calcium bilirubinate gallstones</li><ul> <li>Due to increased conjugated bilirubin in bile from chronic hemolysis</li> </ul><li>Strokes</li> </ol><li>Renal findings in HbAS (also in HbSS)</li><ol type="a"> <li>Sickling may occur in peritubular capillaries in the medulla.</li><ul> <li>Due to the low O<sub>2</sub> tension in the medulla</li> </ul><li>Presents with microhematuria due to infarctions</li><ul> <li>Always order a sickle cell screen in black patients with unexplained hematuria.
<blockquote style="color: blue; ">Sickle cell trait: no anemia; microhematuria</blockquote></li> </ul><li>Renal papillary necrosis may occur.</li><ul> <li>Loss of concentration and dilution</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Sickle cell screen</li><ul> <li>Sodium metabisulfite reduces O<sub>2</sub> tension, which induces sickling.</li> </ul><li>Hb electrophoresis (see <span>[[Fig. 11-8E and F|Figure 11-8]]</span>)
<blockquote style="color: blue; ">HbAS: HbA 55-60%, HbS 40-45%</blockquote></li><ul> <li>(1) HbAS profile-HbA 55% to 60%, HbS 40% to 45%</li><li>(2) HbSS profile-HbS 90% to 95%, HbF 5% to 10%, no HbA
<blockquote style="color: blue; ">HbSS: HbS 90-95%, HbF 5-10%, no HbA</blockquote></li> </ul><li>Peripheral blood findings</li><ul> <li>(1) Normal peripheral blood in HbAS</li><li>(2) In HbSS, there are sickle cells and target cells.</li> </ul><li>Prenatal screening
<blockquote style="color: blue; ">Target cells: excess RBC membrane; sign of hemoglobinopathy or alcohol excess</blockquote></li><ul> <li>Analysis of fetal DNA to detect the point mutation</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Treat infections</li><li>Pain relief (e.g., morphine)</li><li>Transfusion</li><ul> <li>Acute chest syndrome, aplastic crisis</li> </ul> </ol><li>Preventive measures</li><ol type="a"> <li>Hydroxyurea</li><li>Routine immunizations all current</li><li>Pneumococcal vaccine</li><li>Folic acid supplementation</li> </ol> </ol>
</div></html>
<html><a name="HC011048"></a> <br><a name="PB011013"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Decrease in NADPH</b> impairs neutrophils and monocyte killing of bacteria by the O<sub>2</sub>-dependent myeloperoxidase (MPO) system (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>), which requires NADPH as a cofactor for NADPH oxidase.</div><a name="P011065"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>X-linked recessive disorder
<blockquote style="color: blue; ">G6PD deficiency: most common enzyme deficiency causing hemolysis</blockquote></li><li>Subtypes of G6PD deficiency</li><ul> <li>(1) Mediterranean variant in Greeks and Italians</li><li>(2) Black variant</li> </ul><li>Protective against <i>Plasmodium falciparum</i> malaria</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Intrinsic defect with predominantly intravascular hemolysis
<blockquote style="color: blue; ">G6PD deficiency: intrinsic defect, primarily intravascular hemolysis</blockquote></li><ul> <li>Mild component of extravascular hemolysis</li> </ul><li>Decreased synthesis of reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) in the pentose phosphate pathway (<span>[[Fig. 11-29|Figure 11-29]]</span>)</li><ul> <li>(1) GSH normally neutralizes hydrogen peroxide, an oxidant product in RBC metabolism.</li><li>(2) In G6PD deficiency, peroxide oxidizes Hb, which precipitates in the form of Heinz bodies.</li><ul> <li>(a) Heinz bodies damage the RBC membranes causing intravascular hemolysis.</li><li>(b) Heinz bodies removed from RBC membranes by splenic macrophages produce bite cells.</li> </ul> </ul><li>Half-life of G6PD in the Mediterranean variant is markedly reduced.</li><ul> <li>Produces a severe, chronic hemolytic anemia</li> </ul><li>Half-life of G6PD in the black variant is moderately reduced.</li><ul> <li>Episodic type of hemolytic anemia <i>after</i> exposure to oxidant stresses</li> </ul><li>Oxidant stresses inducing hemolysis
<blockquote style="color: blue; ">G6PD deficiency: oxidant damage with Heinz bodies and bite cells</blockquote></li><ul> <li>(1) Infection (most common)</li><li>(2) Drugs
<blockquote style="color: blue; ">G6PD deficiency: O<sub>2</sub>-dependent MPO system dysfunctional; lack of NADPH cofactor</blockquote>
<blockquote style="color: blue; ">Drugs: primaquine, dapsone, sulfonamides</blockquote></li><ul> <li>Examples-primaquine, chloroquine, dapsone, sulfonamides, nitrofurantoin</li> </ul><li>(3) Fava beans (mainly in Mediterranean variant)</li> </ul> </ol><li>Clinical findings</li><ul> <li>Sudden onset of back pain with hemoglobinuria 2 to 3 days after an oxidant stress</li> </ul><li>Laboratory findings</li><ol type="a"> <li>Normocytic anemia</li><li>Heinz bodies (<span>[[Fig. 11-30|Figure 11-30]]</span>)
<blockquote style="color: blue; ">G6PD deficiency: active hemolysis screen with Heinz body prep</blockquote></li><ul> <li>(1) Identified with a supravital stain</li><li>(2) Best screen during active hemolysis</li> </ul><li>RBC enzyme analysis</li><ul> <li>Confirmatory test <i>after</i> hemolysis has subsided
<blockquote style="color: blue; ">Confirmatory test: enzyme analysis</blockquote></li> </ul><li>Peripheral blood findings</li><ul> <li>Bite cells (macrophage removal of membrane; see <span>[[Fig. 11-30|Figure 11-30]]</span>)</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC011049"></a> <br><a name="P011066"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal recessive disease</li><li>Most common enzyme deficiency in the Embden-Meyerhof pathway (<span>[[Fig. 11-31|Figure 11-31]]</span>)</li><ul> <li>PK normally converts phosphoenolpyruvate to pyruvate leading to a net gain of 2 ATP.</li> </ul> </ol><li>Pathogenesis
<blockquote style="color: blue; ">PK deficiency: intrinsic defect, extravascular hemolysis</blockquote></li><ol type="a"> <li>Intrinsic defect with extravascular hemolysis</li><li>Chronic lack of ATP causes membrane damage.</li><ul> <li>Results in dehydration of the RBC (echinocytes; <span>[[Fig. 11-32|Figure 11-32]]</span>)</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Hemolytic anemia with jaundice beginning at birth</li><li>Increase in 2,3-BPG synthesis proximal to enzyme block</li><ul> <li>Right shift of OBC causes increased release of O<sub>2</sub>, which somewhat offsets the clinical effects of the anemia.
<blockquote style="color: blue; ">PK deficiency: ↑ 2,3-BPG right-shifts OBC; offsets clinical effects of anemia</blockquote></li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Normocytic anemia</li><li>RBCs with thorny projections (echinocytes)</li><li>RBC enzyme assay is the confirmatory test.</li> </ol> </ol>
</div></html>
<html><a name="HC011050"></a> <br><a name="P011067"></a><div class="PA" style="color: black; "><ul> <li>Group of extrinsic hemolytic anemias with extravascular or intravascular hemolysis</li><ol type="1"> <li>Classification (<span>[[Table 11-7|Table 11-7. CLASSIFICATION OF IMMUNE HEMOLYTIC ANEMIAS]]</span>)</li><ol type="a"> <li>Autoimmune
<blockquote style="color: blue; ">Immune hemolytic anemia: autoimmune warm type (IgG) most common cause</blockquote></li><ul> <li>(1) Most common type of immune hemolytic anemia</li><li>(2) More common in women than men</li><ul> <li>Systemic lupus erythematosus (SLE) is the most common cause of autoimmune hemolytic anemia (AIHA).
<blockquote style="color: blue; ">Drug-induced: drug adsorption (penicillin), immunocomplex (quinidine), autoantibody (methyldopa)</blockquote></li> </ul><li>(3) 70% are warm type (IgG antibodies) of AIHA</li><li>(4) 30% are cold type (IgM antibodies) of AIHA</li> </ul><li>Drug-induced (see <span>[[Table 11-7|Table 11-7. CLASSIFICATION OF IMMUNE HEMOLYTIC ANEMIAS]]</span>)</li><li>Alloimmune (refer to <span macro="tag [[15 Immunohematology Disorders]] [[Chapter 15]]"></span>)</li> </ol><li>Pathogenesis</li><ol type="a"> <li>IgG-mediated hemolysis</li><ul> <li>(1) RBCs coated by IgG are phagocytosed by splenic macrophages.
<blockquote style="color: blue; ">IgG-mediated: extravascular hemolysis; spherocytosis</blockquote></li><ul> <li>Extravascular hemolysis</li> </ul><li>(2) Spherocytes are produced if a small portion of the membrane is removed.</li> </ul><li>Complement-mediated hemolysis
<blockquote style="color: blue; ">Complement-mediated: intravascular or extravascular hemolysis</blockquote></li><ul> <li>(1) RBCs coated by C3b alone are phagocytosed by liver macrophages.</li><ul> <li>Extravascular hemolysis</li> </ul><li>(2) RBCs coated by C5-C9 (membrane attack complex)</li><ul> <li>Intravascular hemolysis</li> </ul><li>(3) RBCs coated by IgG and C3b are phagocytosed by liver and splenic macrophages (e.g., SLE).</li><ul> <li>Extravascular hemolysis</li> </ul> </ul><li>IgM-mediated hemolysis</li><ul> <li>(1) Extravascular or intravascular depending on the degree of complement activation</li><li>(2) Most often intravascular hemolysis
<blockquote style="color: blue; ">IgM-mediated: intravascular (most common) or extravascular hemolysis</blockquote></li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Jaundice due to unconjugated hyperbilirubinemia</li><ul> <li>Occurs in extravascular types of hemolysis</li> </ul><li>Hepatosplenomegaly</li><ul> <li>Due to work hyperplasia of splenic and liver macrophages</li> </ul><li>Raynaud's phenomenon (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)</li><ul> <li>May occur in cold types of AIHA</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Positive direct antihuman globulin test (DAT; Coombs' test)</li><ul> <li>DAT detects RBCs sensitized with IgG and/or C3b (<span>[[Fig. 11-33A|Figure 11-33]]</span>).
<blockquote style="color: blue; ">DAT: most important marker of immune hemolytic anemia</blockquote></li> </ul><li>Positive indirect antihuman globulin test (indirect Coombs' test; <span>[[Fig. 11-33B|Figure 11-33]]</span>)</li><ul> <li>Detects antibodies in the serum (e.g., anti-D antibodies)</li> </ul><li>Unconjugated hyperbilirubinemia if extravascular hemolysis is present.</li><li>Hemoglobinuria, decreased serum haptoglobin in intravascular hemolysis</li><li>Peripheral blood findings</li><ul> <li>(1) Normocytic anemia</li><li>(2) Spherocytosis due to macrophage removal of RBC membrane (IgG type)</li><li>(3) RBC agglutination (IgM type; <span>[[Fig. 11-34|Figure 11-34]]</span>)</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Discontinue any offensive drug</li><li>Corticosteroids</li><li>Immunosuppressive agents if corticosteroids are not effective</li><li>Splenectomy in selected cases</li><li>Intravenous immunoglobulin</li><ul> <li>(1) IgG coats all the macrophage receptors so they cannot phagocytose RBCs.</li><li>(2) Only used when most of the above treatments are not working</li> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC011051"></a> <br><a name="P011068"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes (<span>[[Table 11-8|Table 11-8. CAUSES OF MICRO- AND MACROANGIOPATHIC HEMOLYTIC ANEMIA]]</span>)
<blockquote style="color: blue; ">MHA: aortic stenosis most common cause</blockquote></li><li>Pathogenesis</li><ol type="a"> <li>Extrinsic defect with intravascular hemolysis
<blockquote style="color: blue; ">MHA: extrinsic, intravascular hemolysis</blockquote></li><li>Microangiopathic</li><ul> <li>Microcirculatory lesions cause RBC fragmentation (schistocytes; <span>[[Fig. 11-35|Figure 11-35]]</span>)
<blockquote style="color: blue; ">Schistocytes: sign of MHA</blockquote></li> </ul><li>Macroangiopathic</li><ul> <li>Hemolytic process caused by valvular defects (e.g., aortic stenosis)</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Normocytic anemia</li><ul> <li>Long-standing hemoglobinuria causes iron deficiency anemia.</li> </ul><li>Decreased serum haptoglobin, hemoglobinuria</li><li>Schistocytes in the peripheral blood</li> </ol> </ol>
</div></html>
<html><a name="HC011052"></a> <br><a name="P011069"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ul> <li>Female <i>Anopheles</i> mosquito transmits <i>Plasmodia</i> to humans.
<blockquote style="color: blue; ">Malaria: <i>Anopheles</i> mosquito</blockquote></li> </ul><li>Pathogenesis</li><ol type="a"> <li>Intraerythrocytic parasite causes intravascular hemolysis.
<blockquote style="color: blue; ">Malaria: intravascular hemolysis correlates with fever spikes</blockquote></li><ul> <li>Correlates with fever spikes</li> </ul><li>Extrinsic defect with predominantly intravascular hemolysis</li><ul> <li>Minor component of extravascular hemolysis
<blockquote style="color: blue; ">Malaria: extrinsic, intravascular hemolysis</blockquote></li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Fever and splenomegaly</li><li><i>Plasmodium vivax</i></li><ul> <li>(1) Most common type
<blockquote style="color: blue; ">Malaria: <i>P. vivax</i> most common type; fever every 48 hours</blockquote></li><li>(2) Duffy (Fy) antigen on RBCs is the binding site.</li><ul> <li>Fy antigen often absent in blacks; protective</li> </ul><li>(3) Tertian fever pattern (every 48 hours)</li> </ul><li><i>Plasmodium falciparum</i></li><ul> <li>(1) Most lethal type
<blockquote style="color: blue; ">Malaria: <i>P. falciparum</i> most lethal type; fever quotidian</blockquote></li><li>(2) Quotidian fever pattern (daily spikes with no pattern)</li> </ul><li><i>Plasmodium malariae</i></li><ul> <li>(1) Association with nephrotic syndrome
<blockquote style="color: blue; ">Malaria: <i>P. malariae</i> fever every 72 hours</blockquote></li><li>(2) Quartan fever pattern (every 72 hours)</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Thick smears identify organisms in RBCs (<span>[[Fig. 11-36|Figure 11-36]]</span>).</li><li>Immunologic tests have excellent sensitivity (98%) and specificity (99%).</li> </ol><li>Medications</li><ol type="a"> <li>Prophylaxis (prevention)
<blockquote style="color: blue; ">Malaria: chloroquine prevention</blockquote></li><ul> <li>(1) Chloroquine</li><ul> <li>(a) Safe during pregnancy</li><li>(b) Kills blood schizonts
<blockquote style="color: blue; ">Malaria Rx <i>P. vivax/ovale</i>: chloroquine + primaquine</blockquote></li><li>(c) Gametocidal to all malaria species <i>except P. falciparum</i></li> </ul><li>(2) Resistant strains <i>P. falciparum</i></li><ul> <li>(a) Use atovaquone-proguanil</li><li>(b) Mefloquine alternative</li> </ul> </ul><li>Treatment <i>P. vivax/ovale</i>
<blockquote style="color: blue; ">Malaria Rx <i>P. falciparum</i>: chloroquine sensitive-chloroquine alone; resistant-quinine sulfate + doxycycline</blockquote></li><ul> <li>Chloroquine + primaquine</li> </ul><li>Treatment <i>P. falciparum</i></li><ul> <li>(1) If chloroquine sensitive-chloroquine without primaquine</li><li>(2) If chloroquine resistant-quinine sulfate + doxycycline</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC011053"></a><span>[[Table 11-9|Table 11-9. SUMMARY OF NORMOCYTIC ANEMIAS]]</span> <br> <br></html>
![[11.VI.A.Pathogenesis of hemolytic anemias]]
<<tiddler [[11.VI.A.Pathogenesis of hemolytic anemias]]>>
![[11.VI.B.Hereditary spherocytosis]]
<<tiddler [[11.VI.B.Hereditary spherocytosis]]>>
![[11.VI.C.Hereditary elliptocytosis]]
<<tiddler [[11.VI.C.Hereditary elliptocytosis]]>>
![[11.VI.D.Paroxysmal nocturnal hemoglobinuria (PNH)]]
<<tiddler [[11.VI.D.Paroxysmal nocturnal hemoglobinuria (PNH)]]>>
![[11.VI.E.Sickle cell anemia]]
<<tiddler [[11.VI.E.Sickle cell anemia]]>>
![[11.VI.F.Glucose-6-phosphate dehydrogenase (G6PD) deficiency]]
<<tiddler [[11.VI.F.Glucose-6-phosphate dehydrogenase (G6PD) deficiency]]>>
![[11.VI.G.Pyruvate kinase (PK) deficiency]]
<<tiddler [[11.VI.G.Pyruvate kinase (PK) deficiency]]>>
![[11.VI.H.Immune hemolytic anemias]]
<<tiddler [[11.VI.H.Immune hemolytic anemias]]>>
![[11.VI.I.Micro- and macroangiopathic hemolytic anemias (MHA)]]
<<tiddler [[11.VI.I.Micro- and macroangiopathic hemolytic anemias (MHA)]]>>
![[11.VI.J.Malaria]]
<<tiddler [[11.VI.J.Malaria]]>>
![[11.VI.K.Summary table of normocytic anemias (Table 11-9)]]
<<tiddler [[11.VI.K.Summary table of normocytic anemias (Table 11-9)]]>>
<html><a name="HC012002"></a> <br><a name="P012001"></a><div class="PA" style="color: black; "><ol type="1"> <li>Defects in leukocyte structure
<blockquote style="color: blue; ">Qualitative WBC defects: defects in structure and function</blockquote></li><ul> <li>Example-membrane fusion defect in Chédiak-Higashi syndrome (refer to <span macro="tag [[01 Cell Injury]] [[Chapters 1]]"></span> and <span macro="tag [[02 Inflammation and Repair]] [[2]]"></span>)</li> </ul><li>Defects in leukocyte function</li><ol type="a"> <li>Leukocyte adhesion defect</li><ul> <li>Example-deficient selectin or CD11a/CD18 (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>)</li> </ul><li>Phagocytosis defect</li><ul> <li>Example-decreased opsonins in Bruton's agammaglobulinemia (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapters 2]]"></span> and <span macro="tag [[03 Immunopathology]] [[3]]"></span>)</li> </ul><li>Microbicidal defect</li><ul> <li>Example-deficiency of myeloperoxidase (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>)</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC012003"></a> <br><a name="PB012001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Job's syndrome</b> is an autosomal recessive disorder of neutrophils, characterized by abnormal chemotaxis leading to "cold" soft tissue abscesses due to <i>Staphylococcus aureus.</i> Patients have red hair, a leonine face, chronic eczema, and increased IgE (hyperimmune E syndrome).</div><a name="P012002"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Qualitative WBC defects: unusual pathogens, "cold" abscesses, frequent infections</blockquote>
<ol type="1"> <li>Unusual pathogens (e.g., coagulase-negative <i>Staphylococcus</i>)</li><li>Frequent infections and growth failure in children</li><li>Lack of an inflammatory response (e.g., production of "cold" abscesses)</li><li>Severe gingivitis</li> </ol>
</div></html>
![[12.I.A.Pathogenesis]]
<<tiddler [[12.I.A.Pathogenesis]]>>
![[12.I.B.Clinical findings]]
<<tiddler [[12.I.B.Clinical findings]]>>
![[12.I.C.Unusual benign leukocyte reactions]]
<<tiddler [[12.I.C.Unusual benign leukocyte reactions]]>>
<html><a name="HC012004"></a> <br><a name="P012003"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Job's syndrome: defect in chemotaxis; ↑ IgE</blockquote>
<ol type="1"> <li>Leukemoid reaction</li><ol type="a"> <li>Absolute leukocyte count usually >50,000 cells/mm<sup>3</sup>
<blockquote style="color: blue; ">Absolute count = % leukocytes × total WBC count</blockquote></li><ul> <li>May involve neutrophils, lymphocytes, or eosinophils</li> </ul><li>Etiology</li><ul> <li>(1) Perforated appendicitis (neutrophils)</li><li>(2) Whooping cough (lymphocytes)</li><li>(3) Cutaneous larva migrans (eosinophils)
<blockquote style="color: blue; ">Leukemoid reaction: benign, exaggerated leukocyte response</blockquote></li> </ul><li>Pathogenesis</li><ul> <li>Exaggerated response to infection</li> </ul> </ol><li>Leukoerythroblastic reaction (<span>[[Fig. 12-1|Figure 12-1]]</span>)</li><ol type="a"> <li>Immature bone marrow cells enter the peripheral blood.</li><li>Pathogenesis</li><ul> <li>(1) Bone marrow infiltrative disease
<blockquote style="color: blue; ">Leukoerythroblastic reaction in woman > 50 years of age: usually due to metastatic breast cancer</blockquote></li><li>(2) Examples-fibrosis, metastatic breast cancer</li> </ul><li>Peripheral blood findings</li><ul> <li>(1) Myeloblasts, progranulocytes</li><li>(2) Nucleated RBCs, tear drop RBCs (if fibrosis is present)</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC012006"></a> <br><a name="P012004"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Neutrophilic leukocytosis: neutrophil count > 7000 cells/mm<sup>3</sup></blockquote>
<ol type="1"> <li>Neutrophilic leukocytosis</li><ol type="a"> <li>Absolute neutrophil count > 7000 cells/mm<sup>3</sup> (see <span>[[Fig. 2-12|Figure 2-12]]</span>)
<blockquote style="color: blue; ">Neutropenia: neutrophil count < 1500 cells/mm<sup>3</sup></blockquote></li><li>Etiology</li><ul> <li>(1) Infection (e.g., acute appendicitis)</li><li>(2) Sterile inflammation with necrosis (e.g., acute myocardial infarction)</li><li>(3) Drugs (e.g., corticosteroids)</li> </ul><li>Pathogenesis</li><ul> <li>(1) Increased bone marrow production or release of neutrophils</li><li>(2) Decreased activation of neutrophil adhesion molecules</li><ul> <li>(a) Fewer neutrophils adhere to endothelial cells</li><li>(b) Examples-corticosteroids, catecholamines, lithium</li> </ul> </ul> </ol><li>Neutropenia</li><ol type="a"> <li>Absolute neutrophil count < 1500 cells/mm<sup>3</sup></li><li>Etiology</li><ul> <li>(1) Aplastic anemia</li><li>(2) Immune destruction</li><ul> <li>Example-systemic lupus erythematosus (SLE)</li> </ul><li>(3) Septic shock</li> </ul><li>Pathogenesis</li><ul> <li>(1) Decreased production</li><li>(2) Increased destruction</li><ul> <li>Destruction by complement, macrophages</li> </ul><li>(3) Activation of neutrophil adhesion molecules</li><ul> <li>(a) Increase the number of neutrophils adhering to endothelium</li><li>(b) Example-endotoxins</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC012007"></a> <br><a name="P012005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Eosinophilia (<span>[[Fig. 12-2A|Figure 12-2]]</span>)
<blockquote style="color: blue; ">Eosinophilia: eosinophil count > 700 cells/mm<sup>3</sup></blockquote></li><ol type="a"> <li>Absolute eosinophil count > 700 cells/mm<sup>3</sup></li><li>Etiology</li><ul> <li>(1) Type I hypersensitivity reaction</li><ul> <li>Examples-bronchial asthma, reaction to penicillin, hay fever</li> </ul><li>(2) Invasive helminthic infection</li><ul> <li>(a) Examples-strongyloidiasis, hookworm infection</li><li>(b) Pinworms and adult ascariasis do <i>not</i> have eosinophilia (noninvasive).</li> </ul><li>(3) Polyarteritis nodosa</li><li>(4) Addison's disease (cortisol deficiency)
<blockquote style="color: blue; ">Eosinophilia: type I hypersensitivity, invasive helminths, hypocortisolism</blockquote></li> </ul><li>Pathogenesis</li><ul> <li>(1) Release of eosinophil chemotactic factor from mast cells</li><ul> <li>Type I hypersensitivity reaction</li> </ul><li>(2) No sequestering of eosinophils in lymph nodes</li><ul> <li>Example-hypocortisolism</li> </ul> </ul> </ol><li>Eosinopenia; etiology:
<blockquote style="color: blue; ">Eosinopenia: hypercortisolism</blockquote></li><ol type="a"> <li>Hypercortisolism</li><ul> <li>Examples-Cushing syndrome, corticosteroids</li> </ul><li>Corticosteroids sequester eosinophils in lymph nodes.</li> </ol> </ol>
</div></html>
![[12.II.A.Disorders involving neutrophils]]
<<tiddler [[12.II.A.Disorders involving neutrophils]]>>
![[12.II.B.Disorders involving eosinophils]]
<<tiddler [[12.II.B.Disorders involving eosinophils]]>>
![[12.II.C.Disorders involving basophils; basophilia]]
<<tiddler [[12.II.C.Disorders involving basophils; basophilia]]>>
![[12.II.D.Disorders involving lymphocytes]]
<<tiddler [[12.II.D.Disorders involving lymphocytes]]>>
![[12.II.E.Disorders involving monocytes; monocytosis]]
<<tiddler [[12.II.E.Disorders involving monocytes; monocytosis]]>>
<html><a name="HC012008"></a> <br><a name="P012006"></a><div class="PA" style="color: black; "><ol type="1"> <li>Absolute basophil count > 110 cells/mm<sup>3</sup> (<span>[[Fig. 12-2B|Figure 12-2]]</span>)
<blockquote style="color: blue; ">Basophilia: consider myeloproliferative disease</blockquote></li><li>Etiology</li><ul> <li>Chronic myeloproliferative disorders (e.g., polycythemia vera)</li> </ul> </ol>
</div></html>
<html><a name="HC012009"></a> <br><a name="P012007"></a><div class="PA" style="color: black; "><ol type="1"> <li>Lymphocytosis
<blockquote style="color: blue; ">Lymphocytosis: lymphocyte count > 4000 cells/mm<sup>3</sup> (adult); >8000 cells/mm<sup>3</sup> (child)</blockquote></li><ol type="a"> <li>Absolute lymphocyte count > 4000 cells/mm<sup>3</sup> in adults or >8000 cells/mm<sup>3</sup> in children (<span>[[Fig. 12-2C|Figure 12-2]]</span>)</li><li>Etiology</li><ul> <li>(1) Viral</li><ul> <li>Examples-mononucleosis, cytomegalovirus (CMV)</li> </ul><li>(2) Bacterial</li><ul> <li>Example-whooping cough</li> </ul><li>(3) Drugs</li><ul> <li>Example-phenytoin</li> </ul><li>(4) Graves' disease</li> </ul><li>Pathogenesis</li><ul> <li>(1) Increased production</li><li>(2) Decreased entry into lymph nodes</li><ul> <li>Example-due to lymphocytosis-promoting factor produced by <i>Bordetella pertussis</i></li> </ul> </ul> </ol><li>Atypical lymphocytosis</li><ol type="a"> <li>Etiology</li><ul> <li>(1) Infection</li><ul> <li>Examples-mononucleosis, viral hepatitis, CMV infection, toxoplasmosis</li> </ul><li>(2) Drugs (e.g., phenytoin)</li> </ul><li>Pathogenesis
<blockquote style="color: blue; ">Atypical lymphocytes: antigenically stimulated</blockquote></li><ul> <li>(1) Antigenically stimulated lymphocytes</li><li>(2) Prominent nucleoli and abundant blue cytoplasm</li> </ul> </ol><li>Infectious mononucleosis
<blockquote style="color: blue; ">Atypical lymphocytosis: EBV, CMV, viral hepatitis, phenytoin</blockquote></li><ol type="a"> <li>Caused by Epstein-Barr virus (EBV)</li><li>Pathogenesis</li><ul> <li>(1) Primarily transmitted by kissing</li><ul> <li>EBV initially replicates epithelial cells in oropharynx.</li> </ul><li>(2) Infection spreads to B cells in lymph nodes</li><ul> <li>(a) Attaches to CD21 receptors on B cells.
<blockquote style="color: blue; ">B cells have CD21 receptor sites for EBV.</blockquote></li><li>(b) Causes B-cell proliferation and increased synthesis of IgM antibodies</li><li>(c) Virus remains dormant in B cells.</li><ul> <li>Recurrences may occur.</li> </ul> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Severe fatigue</li><li>(2) Exudative tonsillitis</li><li>(3) Hepatosplenomegaly</li><ul> <li>Danger of splenic rupture in contact sports</li> </ul><li>(4) Generalized painful lymphadenopathy</li><li>(5) Rash develops if treated with ampicillin.
<blockquote style="color: blue; ">Infectious mononucleosis: rash develops if patient placed on ampicillin</blockquote></li> </ul><li>Laboratory findings</li><ul> <li>(1) Atypical lymphocytosis</li><ul> <li>(a) Usually more than 20% of the total WBC count</li><li>(b) Atypical lymphocytes are antigenically stimulated T cells (<span>[[Fig. 12-3|Figure 12-3]]</span>).</li> </ul><li>(2) Positive heterophil antibody test</li><ul> <li>(a) Initial screening test</li><li>(b) Detects IgM antibodies against horse (most common), sheep, and bovine RBCs
<blockquote style="color: blue; ">Heterophile antibodies: IgM antibodies directed against horse, sheep, bovine</blockquote></li><li>(c) Sensitivity 87%, specificity 91%</li> </ul><li>(3) Antiviral capsid antigen (VCA) antibodies
<blockquote style="color: blue; ">RBCs Anti-VCA-IgG/IgM: excellent test if screening test is negative</blockquote></li><ul> <li>(a) High sensitivity and specificity</li><li>(b) Develops early in the infection</li><li>(c) Persists for life</li> </ul><li>(4) Anti-early antigen (EA) antibodies</li><ul> <li>Increased with chronic infections</li> </ul><li>(5) Anti-Epstein Barr nuclear antigen (EBNA) antibodies</li><ul> <li>(a) High sensitivity and specificity</li><li>(b) Develops late in the infection</li><li>(c) Persists for life</li> </ul><li>(6) Increased serum transaminases from hepatitis</li><ul> <li>Jaundice is rare.</li> </ul> </ul> </ol><li>Lymphopenia
<blockquote style="color: blue; ">Lymphopenia: lymphocyte count < 1500 cells/mm<sup>3</sup> (adult); <3000 cells/mm<sup>3</sup> (child)</blockquote></li><ol type="a"> <li>Absolute lymphocyte count < 1500 cells/mm<sup>3</sup> in adults or <3000 cells/mm<sup>3</sup> in children</li><li>Etiology</li><ul> <li>(1) HIV</li><li>(2) Immunodeficiency
<blockquote style="color: blue; ">Lymphopenia in HIV: lysis of CD4 helper T cells by the virus</blockquote></li><ul> <li>(a) DiGeorge syndrome (T-cell deficiency)</li><li>(b) Severe combined immunodeficiency (B- and T-cell deficiency)</li> </ul><li>(3) Immune destruction (e.g., SLE)</li><li>(4) Corticosteroids (apoptosis)
<blockquote style="color: blue; ">Corticosteroids produce neutrophilic leukocytosis, eosinopenia, and lymphopenia.</blockquote></li><li>(5) Radiation</li><ul> <li>Lymphocytes most sensitive cells to destruction by radiation (refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>)</li> </ul> </ul><li>Pathogenesis</li><ul> <li>(1) Increased destruction</li><ul> <li>Examples-lysis CD4 helper T cells by HIV; apoptosis by corticosteroids; immune destruction (SLE)</li> </ul><li>(2) Decreased production</li><ul> <li>Example-Bruton's agammaglobulinemia</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC012010"></a> <br><a name="P012008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Absolute monocyte count > 800 cells/mm<sup>3</sup> (see <span>[[Fig. 12-2D|Figure 12-2]]</span>)</li><li>Etiology
<blockquote style="color: blue; ">Monocytosis: chronic infection, autoimmune disease, malignancy</blockquote></li><ol type="a"> <li>Chronic infection</li><ul> <li>Examples-tuberculosis, subacute infective endocarditis</li> </ul><li>Autoimmune disease</li><ul> <li>Examples-rheumatoid arthritis, cirrhosis</li> </ul><li>Malignancy</li><ul> <li>Examples-carcinoma, malignant lymphoma</li> </ul> </ol><li>Pathogenesis</li><ul> <li>Response to chronic inflammation or malignancy</li> </ul> </ol>
</div></html>
<html><a name="HC012012"></a> <br><a name="P012012"></a><div class="PA" style="color: black; "><ol type="1"> <li>Malignant diseases of bone marrow stem cells
<blockquote style="color: blue; ">Leukemia: malignant transformation of marrow stem cells</blockquote></li><ul> <li>May involve all cell lines</li> </ul><li>More common in males than females</li><li>Risk factors</li><ol type="a"> <li>Chromosomal abnormalities</li><ul> <li>Examples-Down syndrome, chromosome instability syndromes</li> </ul><li>Ionizing radiation</li><ul> <li>Example-nuclear plant explosion</li> </ul><li>Chemicals</li><ul> <li>Example-benzene for myeloid leukemia</li> </ul><li>Alkylating agents</li><ul> <li>Particularly busulfan</li> </ul><li>Chronic myeloproliferative diseases</li><ul> <li>Example-polycythemia vera</li> </ul><li>Paroxysmal nocturnal hemoglobinuria</li><li>Cigarette smoking</li><li>Immunodeficiency diseases</li><ul> <li>Example-Wiskott-Aldrich syndrome</li> </ul> </ol><li>Age ranges for common leukemias</li><ol type="a"> <li>More common in adults than children</li><li>Newborn to 14 years old
<blockquote style="color: blue; ">ALL: most common leukemia and cancer in children</blockquote></li><ul> <li>(1) Acute lymphoblastic leukemia (ALL)</li><li>(2) Most common leukemia in children</li><li>(3) Most common cancer in children</li> </ul><li>Persons 15 to 39 years old
<blockquote style="color: blue; ">AML: 15-60 years old</blockquote></li><ul> <li>Acute myeloblastic leukemia (AML)</li> </ul><li>Persons 40 to 60 years old</li><ul> <li>(1) AML (>60% of cases)</li><li>(2) Chronic myelogenous leukemia (CML; ∼40% of cases)
<blockquote style="color: blue; ">CML: 40-60+ years old</blockquote></li><ul> <li>May occur in patients > 60 years old</li> </ul> </ul><li>Persons > 60 years of age
<blockquote style="color: blue; ">Most common overall type of leukemia: CLL</blockquote></li><ul> <li>Chronic lymphocytic leukemia (CLL)</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC012013"></a> <br><a name="P012013"></a><div class="PA" style="color: black; "><ol type="1"> <li>Block in stem cell differentiation</li><ol type="a"> <li>Monoclonal proliferation of neoplastic leukocytes behind the block</li><li>Acute leukemia</li><ul> <li>Block occurs at an early stage</li> </ul><li>Chronic leukemia</li><ul> <li>(1) Block occurs at a later stage</li><li>(2) Some evidence of maturation</li> </ul> </ol><li>Leukemic cells
<blockquote style="color: blue; ">Leukemia: arises in the marrow and disseminates</blockquote></li><ol type="a"> <li>Replace most of the bone marrow</li><ul> <li>Replace normal hematopoietic cells</li> </ul><li>Enter the peripheral blood</li><li>Metastasize throughout the body</li> </ol> </ol>
</div></html>
<html><a name="HC012014"></a> <br><a name="P012014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Abrupt onset of signs and symptoms</li><li>Clinical findings</li><ol type="a"> <li>Fever usually from infection</li><li>Bleeding from thrombocytopenia
<blockquote style="color: blue; ">Acute leukemia: abrupt onset</blockquote></li><li>Fatigue from anemia</li> </ol><li>Metastatic disease</li><ol type="a"> <li>Hepatosplenomegaly</li><li>Generalized painless lymphadenopathy</li><li>Central nervous system (CNS) involvement
<blockquote style="color: blue; ">Skin involvement: T cell leukemias</blockquote></li><ul> <li>Especially in ALL</li> </ul><li>Skin involvement
<blockquote style="color: blue; ">CNS, testicle involvement: ALL</blockquote></li><ul> <li>Especially T-cell leukemias</li> </ul><li>Testicles</li><ul> <li>Especially in ALL</li> </ul> </ol><li>Bone pain and tenderness</li><ul> <li>Due to bone marrow expansion by leukemic cells</li> </ul> </ol>
</div></html>
<html><a name="HC012015"></a> <br><a name="P012015"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Most important test for diagnosing leukemia: bone marrow examination</blockquote>
<ol type="1"> <li>Peripheral WBC count</li><ol type="a"> <li>Below 10,000 cells/mm<sup>3</sup> (normal) to >100,000 cells/mm<sup>3</sup></li><li>Blast cells usually present</li><ul> <li>Examples-myeloblasts, lymphoblasts, monoblasts</li> </ul> </ol><li>Normocytic to macrocytic anemia</li><ul> <li>Macrocytic if folate is depleted in production of leukemic cells</li> </ul><li>Thrombocytopenia</li><ul> <li>Usually <100,000 cells/mm<sup>3</sup></li> </ul><li>Bone marrow findings
<blockquote style="color: blue; ">Acute leukemia: key finding of blasts >20% in bone marrow</blockquote></li><ol type="a"> <li>Hypercellular with >20% blasts</li><li>Often completely replaced by blasts</li> </ol> </ol>
</div></html>
<html><a name="HC012016"></a> <br><a name="P012016"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Chronic leukemia: insidious onset</blockquote>
<ol type="a"> <li>Insidious onset</li><li>Slightly more common than acute leukemia</li><li>Hepatosplenomegaly</li><li>Generalized painless lymphadenopathy</li> </ol>
</div></html>
<html><a name="HC012017"></a> <br><a name="P012017"></a><div class="PA" style="color: black; "><ol type="a"> <li>Peripheral WBC count</li><ul> <li>(1) Similar to that of acute leukemia
<blockquote style="color: blue; ">Chronic leukemia: key finding of blasts <10% in bone marrow</blockquote></li><li>(2) Blast cells usually <10%</li><li>(3) Evidence of maturation of cells</li> </ul><li>Normocytic to macrocytic anemia</li><ul> <li>Macrocytic if folate is depleted in production of leukemic cells</li> </ul><li>Thrombocytopenia (usually <100,000 cells/mm<sup>3</sup>)</li><ul> <li><i>Exception</i> in CML, in which thrombocytosis occurs in 40% of cases</li> </ul><li>Bone marrow findings</li><ul> <li>Hypercellular with <10% blasts
<blockquote style="color: blue; ">Acute versus chronic leukemia: bone marrow aspirate with blast count</blockquote></li> </ul> </ol>
</div></html>
<html><a name="HC012018"></a> <br><a name="P012018"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acute lymphoblastic leukemia: 87% 5-year survival rate</li><li>Acute myelogenous leukemia: 21% 5-year survival rate</li><li>Chronic lymphocytic leukemia: 75% 5-year survival rate</li><li>Chronic myelogenous leukemia: 89% 5-year survival rate</li> </ol>
</div></html>
![[12.III.A.Epidemiology]]
<<tiddler [[12.III.A.Epidemiology]]>>
![[12.III.B.Pathogenesis]]
<<tiddler [[12.III.B.Pathogenesis]]>>
![[12.III.C.Clinical findings in acute leukemia]]
<<tiddler [[12.III.C.Clinical findings in acute leukemia]]>>
![[12.III.D.Laboratory findings in acute leukemia]]
<<tiddler [[12.III.D.Laboratory findings in acute leukemia]]>>
![[12.III.E.Clinical findings in chronic leukemia]]
<<tiddler [[12.III.E.Clinical findings in chronic leukemia]]>>
![[12.III.F.Laboratory findings in chronic leukemia]]
<<tiddler [[12.III.F.Laboratory findings in chronic leukemia]]>>
![[12.III.G.Survival rates]]
<<tiddler [[12.III.G.Survival rates]]>>
<html><a name="HC012020"></a> <br><a name="P012019"></a><div class="PA" style="color: black; "><ol type="1"> <li>Myeloid disorders are neoplastic stem cell disorders.
<blockquote style="color: blue; ">Myeloid disorders: neoplastic stem cell disorders</blockquote></li><ul> <li>May involve one or more stem cell lines</li> </ul><li>Classification</li><ol type="a"> <li>Chronic myeloproliferative disorders</li><li>Myelodysplastic syndrome</li><li>Acute myeloblastic leukemia</li> </ol> </ol>
</div></html>
<html><a name="HC012021"></a> <br><a name="P012020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Classification</li><ol type="a"> <li>Polycythemia vera
<blockquote style="color: blue; ">Polycythemia vera: most common chronic myeloproliferative disorder</blockquote></li><li>Chronic myelogenous leukemia</li><li>Myeloid metaplasia with myelofibrosis</li><li>Essential thrombocythemia</li> </ol><li>General characteristics</li><ol type="a"> <li>Splenomegaly</li><li>Propensity for reactive bone marrow fibrosis ("spent phase")</li><li>Propensity for transformation to acute leukemia</li> </ol><li>Polycythemia (<span>[[Fig. 12-4|Figure 12-4]]</span>)</li><ol type="a"> <li>Increased hemoglobin (Hb), hematocrit (Hct), and RBC count</li><li>Plasma volume (PV) varies with the type of polycythemia.</li><li>RBC count versus RBC mass</li><ul> <li>(1) RBC count is the number of RBCs per microliter (μL) of blood.</li><li>(2) RBC mass is the total number of RBCs in the body in mL/kg.</li><li>(3) RBC count is the ratio of RBC mass to PV.</li><ul> <li><span>[[Figure 12-4A|Figure 12-4]]</span> shows the normal relationship between RBC count, RBC mass, PV, erythropoietin (EPO), and O<sub>2</sub> saturation (Sa<span style="font-variant:small-caps;">o</span><sub>2</sub>).
<blockquote style="color: blue; ">RBC count = RBC mass/PV</blockquote></li> </ul> </ul><li>Relative polycythemia (<span>[[Fig. 12-4B|Figure 12-4]]</span>)</li><ul> <li>(1) Overall most common polycythemia</li><li>(2) Increased RBC count due to a decrease in PV
<blockquote style="color: blue; ">Relative polycythemia: ↑ RBC count; ↓ PV; normal RBC mass, Sa<span style="font-variant:small-caps;">o</span><sub>2</sub>, EPO</blockquote></li><ul> <li>Example-volume depletion from sweating</li> </ul><li>(3) RBC mass is normal.</li><ul> <li><i>No</i> increase in bone marrow production of RBCs</li> </ul><li>(4) EPO and Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> are normal.</li><li>(5) Fluid replacement corrects the polycythemia.</li> </ul><li>Absolute polycythemia</li><ul> <li>(1) Increase in bone marrow production of RBCs</li><ul> <li>Increased RBC count and RBC mass</li> </ul><li>(2) Appropriate absolute polycythemia (<span>[[Fig. 12-4C|Figure 12-4]]</span>)
<blockquote style="color: blue; ">Appropriate absolute polycythemia: ↑ RBC mass, EPO; normal PV; ↓ Sa<span style="font-variant:small-caps;">o</span><sub>2</sub></blockquote></li><ul> <li>(a) There is a hypoxic stimulus for EPO release.</li><li>(b) Examples-primary lung disease, cyanotic congenital heart disease, high altitude</li><li>(c) Decreased O<sub>2</sub> saturation (Sa<span style="font-variant:small-caps;">o</span><sub>2</sub>)</li><li>(d) Increased RBC count, RBC mass, EPO</li><li>(e) Normal PV</li> </ul><li>(3) Inappropriate absolute polycythemia: ectopic EPO production (<span>[[Fig. 12-4D|Figure 12-4]]</span>)</li><ul> <li>(a) No hypoxic stimulus for EPO release</li><ul> <li>Ectopic release of EPO from renal cell carcinoma
<blockquote style="color: blue; ">Inappropriate absolute polycythemia (ectopic secretion EPO): ↑ RBC mass, EPO; normal PV, normal Sa<span style="font-variant:small-caps;">o</span><sub>2</sub></blockquote>
<blockquote style="color: blue; ">Inappropriate absolute polycythemia (PRV): ↑ RBC mass, ↓ EPO; ↑ PV, normal Sa<span style="font-variant:small-caps;">o</span><sub>2</sub></blockquote></li> </ul><li>(b) Increased RBC count, RBC mass, EPO</li><li>(c) Normal PV and Sa<span style="font-variant:small-caps;">o</span><sub>2</sub></li> </ul> </ul> </ol><li>Polycythemia vera (<span>[[Fig. 12-4E|Figure 12-4]]</span>)</li><ol type="a"> <li>Inappropriate absolute polycythemia</li><li>Pathogenesis</li><ul> <li>(1) Clonal expansion of the myeloid stem cell</li><li>(2) Most due to mutation of <i>JAK2</i> gene on short arm of chromosome 9</li><ul> <li>Same mutation may manifest as myelofibrosis and myeloid metaplasia or essential thrombocythemia
<blockquote style="color: blue; ">PRV: mutation of <i>JAK2</i> gene</blockquote></li> </ul><li>(3) Increased production of RBCs, granulocytes (neutrophils, eosinophils, basophils), mast cells, and platelets</li> </ul><li>Clinical findings</li><ul> <li>(1) Hepatosplenomegaly</li><li>(2) Ruddy (plethoric) face</li><ul> <li>Due to vessel congestion</li> </ul><li>(3) Thrombotic events
<blockquote style="color: blue; ">PRV: thrombotic events</blockquote></li><ul> <li>(a) Due to hyperviscosity related to increased RBC count</li><li>(b) Examples-hepatic vein thrombosis, dural sinus thrombosis, retinal vein thrombosis</li> </ul><li>(4) Impaired CNS circulation</li><ul> <li>(a) Headache</li><li>(b) Blurred vision</li><li>(c) Retinal vein engorgement</li><li>(d) Vertigo</li><li>(e) Transient ischemic attack</li><li>(f) Stroke</li> </ul><li>(5) Signs of increased histamine released from mast cells
<blockquote style="color: blue; ">Polycythemia vera: pruritis after bathing, mast cell release of histamine</blockquote></li><ul> <li>(a) Pruritus after bathing</li><ul> <li>Very common initial complaint; mast cells degranulate with change in skin temperature</li> </ul><li>(b) Peptic ulcer disease</li><ul> <li>Histamine stimulates production of gastric acid.</li> </ul> </ul><li>(6) Gout</li><ul> <li>(a) Increased breakdown of nucleated cells with release of purines</li><li>(b) Purines are converted to uric acid.</li> </ul> </ul><li>Laboratory findings in polycythemia vera</li><ul> <li>(1) Increased RBC count, RBC mass, PV</li><li>(2) Decreased EPO
<blockquote style="color: blue; ">Polycythemia vera: serum EPO best initial test</blockquote></li><ul> <li>Best initial test for polycythemia vera</li> </ul><li>(3) Normal Sa<span style="font-variant:small-caps;">o</span><sub>2</sub>
<blockquote style="color: blue; ">Polycythemia vera: only polycythemia with ↑ PV and ↓ EPO</blockquote></li> </ul><li>Major and minor criteria for diagnosing polycythemia vera</li><ul> <li>Three major criteria or first two major criteria plus two minor criteria</li> </ul><ul> <li>(1) Major criteria</li><ul> <li>(a) Increased RBC mass: >36 mL/kg, >32 mL/kg in women</li><li>(b) Normal Sa<span style="font-variant:small-caps;">o</span><sub>2</sub> (>92%)</li><li>(c) Splenomegaly</li> </ul><li>(2) Minor criteria</li><ul> <li>(a) Absolute leukocytosis: >12,000 cells/mm<sup>3</sup></li><li>(b) Thrombocytosis: >400,000 cells/mm<sup>3</sup></li><li>(c) Increased serum leukocyte alkaline phosphatase: >100 score</li><li>(d) Increased serum vitamin B<sub>12</sub>: >900 pg/mL or vitamin B<sub>12</sub> binding protein > 2200 pg/mL</li> </ul><li>(3) Hypercellular bone marrow with fibrosis in later stages</li> </ul><li>Treatment</li><ul> <li>(1) Nonpharmacologic</li><ul> <li>Phlebotomy to reduce hyperviscosity
<blockquote style="color: blue; ">Polycythemia vera: phlebotomy reduces viscosity-induced thrombosis</blockquote></li> </ul><li>(2) Pharmacologic</li><ul> <li>(a) Hydroxyurea + phlebotomy</li><li>(b) Interferon-α</li> </ul> </ul><li>Prognosis</li><ul> <li>Median survival 6 to 18 months</li> </ul><li>Summary table of the polycythemias (<span>[[Table 12-1|Table 12-1. LABORATORY FINDINGS IN POLYCYTHEMIAS]]</span>)</li> </ol><li>CML</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Usually occurs 40 to 60+ years of age
<blockquote style="color: blue; ">CML: 40-60+ years of age</blockquote></li><li>(2) Accounts for 15% of adult leukemias</li><li>(3) Risk factors</li><ul> <li>Exposure to ionizing radiation and benzene</li> </ul> </ul><li>Pathogenesis</li><ul> <li>(1) Neoplastic clonal expansion of the pluripotential stem cell</li><ul> <li>This stem cell has the capacity to differentiate into a lymphoid or myeloid stem cell.</li> </ul><li>(2) t9;22 translocation of <i>ABL</i> proto-oncogene</li><ul> <li>(a) Proto-oncogene fuses with the break cluster region (BCR) on chromosome 22 (<i>BCR-ABL</i> fusion gene).</li><li>(b) Chromosome 22 with translocation is called Philadelphia chromosome.
<blockquote style="color: blue; ">Philadelphia chromosome = chromosome 22 with translocation</blockquote></li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Hepatosplenomegaly and generalized painless lymphadenopathy</li><ul> <li>Due to metastasis</li> </ul><li>(2) Blast crisis</li><ul> <li>(a) Usually occurs in ∼5 years</li><li>(b) Increase in numbers of myeloblasts or lymphoblasts
<blockquote style="color: blue; ">CML blast crisis: myeloblasts or lymphoblasts; no Auer rods</blockquote></li><li>(c) Myeloblasts do <i>not</i> contain Auer rods (see below).</li> </ul> </ul><li>Laboratory findings</li><ul> <li>(1) Peripheral WBC count 50,000 to 200,000 cells/mm<sup>3</sup> (<span>[[Fig. 12-5|Figure 12-5]]</span>)</li><ul> <li>(a) Myeloid series in all stages of development</li><li>(b) Basophilia</li> </ul><li>(2) Normocytic to macrocytic anemia</li><ul> <li>Macrocytic if folate is depleted in the production of leukemic cells</li> </ul><li>(3) Platelet count</li><ul> <li>(a) Thrombocytosis in 40% to 50% of cases (uncommon in leukemia)
<blockquote style="color: blue; ">CML: only leukemia with thrombocytosis</blockquote></li><li>(b) Thrombocytopenia in the remainder of cases</li> </ul><li>(4) Bone marrow findings</li><ul> <li>(a) Myeloblasts < 10%</li><li>(b) Hypercellular</li> </ul><li>(5) Positive Philadelphia chromosome (95% of cases)</li><ul> <li>(a) It is <i>not</i> specific for CML and is present in other leukemias (e.g., ALL).</li><li>(b) It is <i>not</i> lost during therapy unless α-interferon is used.</li> </ul><li>(6) <i>BCR-ABL</i> fusion gene (100% of cases)
<blockquote style="color: blue; "><i>BCR-ABL</i> fusion gene: most sensitive and specific test for CML</blockquote></li><ul> <li>Fusion gene is the most sensitive and specific test for CML.</li> </ul><li>(7) Decreased leukocyte alkaline phosphatase (LAP) score</li><ul> <li>LAP is absent in neoplastic granulocytes and present in benign granulocytes.</li> </ul> </ul><li>Treatment</li><ul> <li>(1) Imatinib mesylate</li><ul> <li>(a) Oral tyrosine kinase inhibitor</li><li>(b) <35% Philadelphia chromosome positive cells after treatment</li> </ul><li>(2) Allogenic stem cell transplantation</li> </ul><li>Prognosis</li><ul> <li>∼90% 5-year survival rate</li> </ul> </ol><li>Myelofibrosis and myeloid metaplasia (MMM)</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Occurs in patients > 50 years old</li><li>(2) Most common cause of splenomegaly in this group</li> </ul><li>Pathogenesis</li><ul> <li>(1) Clonal myeloproliferative disease
<blockquote style="color: blue; ">MMM: mutation of <i>JAK2</i> gene</blockquote></li><li>(2) Most due to mutation of <i>JAK2</i> gene on short arm of chromosome 9</li><ul> <li>Same mutation may manifest as polycythemia vera or thrombocythemia.</li> </ul><li>(3) Ineffective erythropoiesis, dysplastic megakaryocytes, immature granulocytes, reactive myelofibrosis</li><ul> <li>Marrow fibrosis occurs earlier than in the other chronic myeloproliferative diseases.</li> </ul><li>(4) Hematopoiesis moves to the spleen, liver, and other sites (extramedullary hematopoiesis, EMH).
<blockquote style="color: blue; ">MMM: EMH; marrow fibrosis; massive splenomegaly</blockquote></li> </ul><li>Clinical findings</li><ul> <li>(1) Massive splenomegaly with portal hypertension</li><li>(2) Splenic infarcts with left-sided pleural effusions</li> </ul><li>Laboratory findings</li><ul> <li>(1) Bone marrow fibrosis (<span>[[Fig. 12-6|Figure 12-6]]</span>)</li><li>(2) Peripheral WBC count 10,000 to 50,000 cells/mm<sup>3</sup></li><li>(3) Normocytic anemia
<blockquote style="color: blue; ">MMM: tear drop RBCs; leukoerythroblastic smear</blockquote></li><ul> <li>(a) Tear drop cells (damaged RBCs)</li><li>(b) Leukoerythroblastic reaction (see <span>[[Fig. 12-1|Figure 12-1]]</span>)</li> </ul><li>(4) Platelet count is variable.</li><ul> <li>Platelets have abnormal morphology.</li> </ul><li>(5) Serum leukocyte alkaline phosphatase score is normal to increased.</li><ul> <li>(a) Decreased in chronic myelogenous leukemia</li><li>(b) Increased in polycythemia vera</li> </ul> </ul><li>Treatment</li><ul> <li>(1) Hydroxyurea</li><li>(2) Interferon-α</li> </ul> </ol><li>Essential thrombocythemia (ET)</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Clonal myeloproliferative disease with excess formation of dysplastic and defective platelets
<blockquote style="color: blue; ">ET: dysplastic/nonfunctional platelets; ↑ platelets</blockquote></li><li>(2) Most due to mutation of <i>JAK2</i> gene on short arm of chromosome 9</li><ul> <li>Same mutation may manifest as polycythemia vera or myelofibrosis and myeloid metaplasia.
<blockquote style="color: blue; ">ET: mutation of <i>JAK2</i> gene</blockquote></li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Bleeding</li><ul> <li>(a) Usually gastrointestinal with concomitant iron deficiency</li><li>(b) Platelets nonfunctional</li> </ul><li>(2) Splenomegaly</li> </ul><li>Laboratory findings</li><ul> <li>(1) Thrombocytosis</li><ul> <li>(a) Platelets > 600,000 cells/mm<sup>3</sup>; often >1 million cells/mm<sup>3</sup></li><li>(b) Platelet morphology is abnormal.</li> </ul><li>(2) Mild neutrophilic leukocytosis</li><li>(3) Basophilia</li><li>(4) Hypercellular bone marrow with abnormal megakaryocytes</li> </ul><li>Treatment</li><ul> <li>Hydroxyurea</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC012022"></a> <br><a name="P012021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ul> <li>Usually occurs in men between 50 and 80 years old
<blockquote style="color: blue; ">MDS: cytopenias; hypercellular marrow</blockquote></li> </ul><li>Pathogenesis</li><ol type="a"> <li>Group of acquired clonal disorders affecting stem cells</li><li>Cytopenias and hypercellular marrow</li><li>Classification</li><ul> <li>(1) Refractory anemia</li><li>(2) Refractory anemia with ringed sideroblasts</li><li>(3) Chronic myelomonocytic leukemia</li><li>(4) Refractory anemia with excess blasts in transformation</li> </ul><li>Frequently progresses to acute myeloblastic leukemia (AML; 30% of cases)
<blockquote style="color: blue; ">MDS: >30% progress to acute leukemia</blockquote></li> </ol><li>Laboratory findings</li><ol type="a"> <li>Severe pancytopenia</li><ul> <li>(1) Normocytic to macrocytic anemia</li><ul> <li>Dimorphic RBC population (microcytic and macrocytic)</li> </ul><li>(2) Leukoerythroblastic reaction</li> </ul><li>Bone marrow findings</li><ul> <li>(1) Ringed sideroblasts (nucleated RBCs with excess iron)</li><li>(2) Myeloblasts < 20%</li><ul> <li>If >20%, disease is progressing to AML.</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC012023"></a> <br><a name="P012022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Usually occurs between 15 and 59 years of age</li><li>French-American-British (FAB) classification is used (<span>[[Table 12-2|Table 12-2. FRENCH-AMERICAN-BRITISH CLASSIFICATION OF ACUTE MYELOBLASTIC LEUKEMIA (AML)]]</span>).</li> </ol><li>Cytogenetic abnormalities are common.</li><ul> <li>Example-t(15;17) in acute promyelocytic leukemia (M3)
<blockquote style="color: blue; ">Acute promyelocytic leukemia: t(15;17)</blockquote></li> </ul><li>Clinical findings</li><ol type="a"> <li>Disseminated intravascular coagulation (DIC) is common.</li><ul> <li>Invariable in acute promyelocytic leukemia
<blockquote style="color: blue; ">Acute monocyte leukemia: gum infiltration</blockquote></li> </ul><li>Gum infiltration is common in acute monocytic leukemia (M5).</li> </ol><li>Auer rods
<blockquote style="color: blue; ">AML: Auer rods in the cytoplasm of myeloblasts</blockquote></li><ol type="a"> <li>Splinter-shaped to rod-shaped structures in the cytosol of myeloblasts</li><ul> <li>Auer rods are fused azurophilic granules (<span>[[Fig. 12-7|Figure 12-7]]</span>).</li> </ul><li>Only present in AML (M2 and M3)
<blockquote style="color: blue; ">Auer rods: only in AML; not in CML</blockquote></li><ul> <li>They are <i>not</i> present in myeloblasts in CML.</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Induction therapy: cytarabine + daunorubicin</li><li>Consolidation therapy: aggressive chemotherapy with or without radiation</li><li>Maintenance therapy: cytarabine</li> </ol> </ol>
</div></html>
![[12.IV.A.Overview]]
<<tiddler [[12.IV.A.Overview]]>>
![[12.IV.B.Chronic myeloproliferative disorders]]
<<tiddler [[12.IV.B.Chronic myeloproliferative disorders]]>>
![[12.IV.C.Myelodysplastic syndromes (MDS)]]
<<tiddler [[12.IV.C.Myelodysplastic syndromes (MDS)]]>>
![[12.IV.D.Acute myeloblastic leukemia]]
<<tiddler [[12.IV.D.Acute myeloblastic leukemia]]>>
<html><a name="HC012025"></a> <br><a name="P012026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common leukemia and cancer in children (newborn to 14 years of age)
<blockquote style="color: blue; ">ALL: most common cancer and leukemia in children</blockquote></li><li>Subtypes</li><ul> <li>(1) Early pre-B-cell ALL (80%)</li><li>(2) Pre-B-, B-, and T-cell ALL</li> </ul> </ol><li>Pathogenesis</li><ul> <li>Clonal lymphoid stem cell disease
<blockquote style="color: blue; ">ALL: CD10 and TdT positive; most common type</blockquote></li> </ul><li>Early pre-B-cell ALL</li><ol type="a"> <li>Positive marker studies for common ALL antigen (CALLA, CD10)
<blockquote style="color: blue; ">ALL: t(12;21) offers favorable prognosis</blockquote></li><li>Positive marker studies for terminal deoxynucleotidyl transferase (TdT)</li><li>t(12;21) translocation offers a favorable prognosis.</li><li>Greater than 90% achieve complete remission.</li><ul> <li>At least two thirds of patients can be considered cured.
<blockquote style="color: blue; ">ALL: around two thirds cured</blockquote></li> </ul> </ol><li>T-cell ALL</li><ul> <li>CD10 negative and TdT positive</li> </ul><li>Clinical findings</li><ol type="a"> <li>Metastatic sites similar to those of AML</li><li>B-cell types</li><ul> <li>Commonly metastasize to the CNS and testicles</li> </ul><li>T-cell type</li><ul> <li>Presents as anterior mediastinal mass or acute leukemia</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Peripheral WBC count 10,000 to 100,000 cells/mm<sup>3</sup> (<span>[[Fig. 12-8|Figure 12-8]]</span>)</li><ul> <li>Over 20% lymphoblasts in peripheral blood</li> </ul><li>Normocytic anemia with thrombocytopenia</li><li>Bone marrow findings</li><ul> <li>Bone marrow often totally replaced by lymphoblasts</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Induction therapy: vincristine, prednisone, <span style="font-variant:small-caps;">l</span>-asparaginase</li><li>Consolidation therapy: aggressive chemotherapy with or without radiation</li><li>Maintenance therapy: methotrexate + 6-mercaptopurine</li><li>Bone marrow transplantation is an option.</li> </ol> </ol>
</div></html>
<html><a name="HC012026"></a> <br><a name="P012027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Malignant leukemia associated with human T-cell leukemia virus (HTLV-1)
<blockquote style="color: blue; ">Adult T-cell leukemia: association with HTLV-1</blockquote></li><li>May present as a malignant lymphoma</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Activation of <i>TAX</i> gene, which inhibits the <i>TP53</i> suppressor gene
<blockquote style="color: blue; "><i>TAX</i> gene: inhibits <i>TP53</i> suppressor gene</blockquote></li><li>Leads to monoclonal proliferation of neoplastic CD4 helper T cells</li> </ol><li>Clinical findings</li><ol type="a"> <li>Hepatosplenomegaly and generalized lymphadenopathy</li><li>Skin infiltration
<blockquote style="color: blue; ">Adult T-cell leukemia: skin lesions; lytic bone lesions with hypercalcemia</blockquote></li><ul> <li>Common finding in all T-cell malignancies</li> </ul><li>Lytic bone lesions</li><ul> <li>(1) Due to lymphoblast release of osteoclast-activating factor</li><li>(2) Associated with hypercalcemia</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Peripheral WBC count 10,000 to 50,000 cells/mm<sup>3</sup></li><ul> <li>(1) Over 20% lymphoblasts</li><li>(2) Positive CD4 marker study</li><li>(3) Negative for TdT</li> </ul><li>Normocytic anemia and thrombocytopenia</li><li>Bone marrow findings</li><ul> <li>Replaced by CD4 lymphoblasts</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC012027"></a> <br><a name="P012028"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology
<blockquote style="color: blue; ">CLL: most common leukemia</blockquote></li><ol type="a"> <li>Occurs in individuals > 60 years old</li><li>Most common overall leukemia</li><li>Most common cause of generalized lymphadenopathy in the same age bracket
<blockquote style="color: blue; ">CLL: most common cause of generalized lymphadenopathy in those >60 years old</blockquote></li> </ol><li>Pathogenesis</li><ul> <li>Neoplastic disorder of virgin B cells (B cells that cannot differentiate into plasma cells)</li> </ul><li>Clinical findings</li><ol type="a"> <li>Generalized lymphadenopathy</li><li>Metastatic sites similar to those of AML</li><li>Increased incidence of immune hemolytic anemia</li><ul> <li>Both warm (IgG) and cold (IgM) types</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Peripheral WBC count 15,000 to 200,000 cells/mm<sup>3</sup> (<span>[[Fig. 12-9|Figure 12-9]]</span>)</li><li>Lymphoblasts < 10%
<blockquote style="color: blue; ">CLL: hypogammaglobu-linemia; smudge cells</blockquote></li><li>Neutropenia</li><li>Numerous "smudge" cells (fragile leukemic cells)</li><li>Normocytic anemia (50% of cases) and thrombocytopenia (40% of cases)</li><li>Bone marrow findings</li><ul> <li>(1) Usually completely replaced by neoplastic B cells</li><li>(2) Lymphoblasts < 10%</li> </ul><li>Hypogammaglobulinemia is common.</li><ul> <li>Neoplastic B cells do not form plasma cells</li> </ul> </ol><li>Treatment</li><ul> <li>Chlorambucil</li> </ul> </ol>
</div></html>
<html><a name="HC012028"></a> <br><a name="P012029"></a><div class="PA" style="color: black; "><ol type="1"> <li>Type of B-cell leukemia</li><ul> <li>Most common in middle-aged men</li> </ul><li>Clinical findings</li><ol type="a"> <li>Splenomegaly (90% of cases)
<blockquote style="color: blue; ">HCL: spleen primary site for neoplastic cells</blockquote></li><ul> <li>Primary site for proliferation of neoplastic cells</li> </ul><li>Absence of lymphadenopathy
<blockquote style="color: blue; ">HCL: absence of lymphadenopathy</blockquote></li><ul> <li>Only leukemia <i>without</i> lymphadenopathy</li> </ul><li>Hepatomegaly (20% of cases)</li><li>Autoimmune vasculitis and arthritis</li> </ol><li>Laboratory findings</li><ol type="a"> <li>Pancytopenia</li><li>Leukemic cells have hair-like projections (<span>[[Fig. 12-10|Figure 12-10]]</span>)</li><li>Bone marrow</li><ul> <li>(1) Packed with neoplastic cells</li><li>(2) Increased reticulin fibers</li> </ul><li>Positive tartrate-resistant acid phosphatase (TRAP) stain
<blockquote style="color: blue; ">HCL: positive TRAP stain</blockquote></li> </ol><li>Treatment</li><ul> <li>Drugs of choice are purine analogs; e.g., 2-chloro-2 deoxyadenosine
<blockquote style="color: blue; ">HCL: dramatic response to purine nucleosides</blockquote></li> </ul> </ol>
</div></html>
<html><a name="HC012029"></a><span>[[Table 12-3|Table 12-3. SUMMARY OF ACUTE AND CHRONIC LYMPHOID LEUKEMIAS]]</span> <br> <br></html>
![[12.V.A.Acute lymphoblastic leukemia]]
<<tiddler [[12.V.A.Acute lymphoblastic leukemia]]>>
![[12.V.B.Adult T-cell leukemia]]
<<tiddler [[12.V.B.Adult T-cell leukemia]]>>
![[12.V.C.Chronic lymphocytic leukemia]]
<<tiddler [[12.V.C.Chronic lymphocytic leukemia]]>>
![[12.V.D.Hairy cell leukemia (HCL)]]
<<tiddler [[12.V.D.Hairy cell leukemia (HCL)]]>>
![[12.V.E.Summary table of the lymphoid leukemias (Table 12-3)]]
<<tiddler [[12.V.E.Summary table of the lymphoid leukemias (Table 12-3)]]>>
<html><a name="HC013002"></a> <br><a name="P013001"></a><div class="PA" style="color: black; "><ol type="1"> <li>Locations</li><ol type="a"> <li>Regional lymph nodes</li><li>Tonsils and adenoids (Waldeyer's ring)</li><li>Peyer's patches and appendix</li><li>White pulp of the spleen</li> </ol><li>B cells (<span>[[Fig. 13-1|Figure 13-1]]</span>)
<blockquote style="color: blue; ">B cells: germinal follicles</blockquote></li><ol type="a"> <li>Germinal follicles in lymph nodes</li><li>Peripheral areas of spleen white pulp</li> </ol><li>T cells (see <span>[[Fig. 13-1|Figure 13-1]]</span>)
<blockquote style="color: blue; ">T cells: paracortex, thymus</blockquote></li><ol type="a"> <li>Paracortex (parafollicular) in lymph nodes</li><li>Periarteriolar sheath in spleen</li><li>Thymus</li> </ol><li>Histiocytes</li><ol type="a"> <li>Sinuses in lymph nodes (see <span>[[Fig. 13-1|Figure 13-1]]</span>)
<blockquote style="color: blue; ">Histiocytes: sinuses, skin (Langerhans cell)</blockquote></li><li>Skin (Langerhans cells)</li> </ol><li>Locations of lymphoid disorders (<span>[[Fig. 13-2|Figure 13-2]]</span>)</li> </ol>
</div></html>
<html><a name="HC013003"></a><span>[[Fig. 13-3|Figure 13-3]]</span> <br> <br><a name="P013002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Age</li><ul> <li>(1) Patients < 30 years old
<blockquote style="color: blue; ">Nodule enlargement: <30 usually benign; >30 usually malignant</blockquote></li><ul> <li>Nodal enlargement is usually benign disease (∼80% of cases).</li> </ul><li>(2) Patients > 30 years old</li><ul> <li>Nodal enlargement is usually malignant disease (∼60% of cases).</li> </ul> </ul><li>Causes</li><ul> <li>(1) Reactive lymphadenitis</li><ul> <li>Hyperplasia of B cells, T cells, or histiocytes</li> </ul><li>(2) Infiltrative disease</li><ul> <li>Examples-metastasis (most common), malignant lymphoma</li> </ul> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Painful nodes imply inflammation (e.g., infection)
<blockquote style="color: blue; ">Painful lymphadenopathy: inflammation</blockquote></li><ul> <li>(1) Localized</li><ul> <li>(a) Drain sites of infection (e.g., tonsillitis)</li><li>(b) Most common sites</li><ul> <li>Anterior cervical nodes, inguinal nodes</li> </ul> </ul><li>(2) Generalized</li><ul> <li>(a) Systemic disease</li><li>(b) Examples-infectious mononucleosis, systemic lupus erythematosus (SLE)</li> </ul> </ul><li>Painless nodes imply a malignancy.
<blockquote style="color: blue; ">Painless lymphadenopathy: metastasis or primary malignant lymphoma</blockquote></li><ul> <li>(1) Lymph nodes are indurated and often fixed to surrounding tissue.</li><li>(2) Localized</li><ul> <li>(a) Nodes draining a primary cancer site</li><ul> <li>Example-axillary nodes in breast cancer</li> </ul><li>(b) Hodgkin's lymphoma (HL)</li> </ul><li>(3) Generalized</li><ul> <li>(a) Metastasis in leukemia</li><li>(b) Follicular B-cell lymphoma</li> </ul> </ul><li>Key nodal groups involved in primary or metastatic cancer</li><ul> <li>(1) Submental</li><ul> <li>Metastatic squamous cell carcinoma in the floor of the mouth</li> </ul><li>(2) Cervical</li><ul> <li>(a) Metastatic head and neck tumors (e.g., larynx; thyroid, nasopharynx)</li><li>(b) HL</li> </ul><li>(3) Left-sided supraclavicular (Virchow's nodes)
<blockquote style="color: blue; ">Left supraclavicular node metastasis: stomach or pancreatic carcinoma</blockquote></li><ul> <li>Metastatic abdominal cancers (e.g., stomach; pancreas)</li> </ul><li>(4) Right-sided supraclavicular</li><ul> <li>(a) Metastatic lung and esophageal cancers</li><li>(b) HL</li> </ul><li>(5) Axillary</li><ul> <li>Metastatic breast cancer</li> </ul><li>(6) Epitrochlear</li><ul> <li>(a) Unilateral-hand infection, non-Hodgkin's lymphoma (NHL)</li><li>(b) Bilateral-sarcoidosis</li> </ul><li>(7) Hilar
<blockquote style="color: blue; ">Hilar nodes metastasis: lung cancer</blockquote></li><ul> <li>Metastatic lung cancer</li> </ul><li>(8) Mediastinal</li><ul> <li>(a) Metastatic lung cancer</li><li>(b) HL (particularly nodular sclerosing type)</li><li>(c) T-cell lymphoblastic lymphoma</li> </ul><li>(9) Tonsillar (superior jugular node)</li><ul> <li>Metastatic squamous cancers in oral cavity</li> </ul><li>(10) Para-aortic
<blockquote style="color: blue; ">Para-aortic node metastasis: testicular cancer</blockquote></li><ul> <li>(a) Metastatic testicular cancer</li><ul> <li>Testicles migrate to the scrotum from an abdominal location.</li> </ul><li>(b) Burkitt's lymphoma</li> </ul><li>(11) Inguinal</li><ul> <li>Metastatic vulvar and penis cancers</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC013004"></a> <br><a name="P013003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Follicular hyperplasia</li><ol type="a"> <li>B-cell antigenic response (see <span>[[Fig. 13-1|Figure 13-1]]</span>)</li><ul> <li>(1) Germinal follicles are sharply demarcated from the paracortex.
<blockquote style="color: blue; ">Follicular hyperplasia: prominent germinal follicles</blockquote></li><li>(2) Cells are in different stages of development.</li> </ul><li>Examples</li><ul> <li>(1) Early stages of HIV infection</li><li>(2) Examples-rheumatoid arthritis, SLE</li> </ul> </ol><li>Paracortical hyperplasia</li><ol type="a"> <li>T-cell antigenic response</li><li>Dermatopathic lymphadenitis
<blockquote style="color: blue; ">Dermatopathic lymphadenitis: melanin pigment</blockquote></li><ul> <li>(1) Nodes draining chronic dermatitis (e.g., psoriasis)</li><li>(2) Nodes contain macrophages with phagocytosis of melanin pigment.</li><ul> <li>Simulates metastatic malignant melanoma</li> </ul> </ul><li>Examples-phenytoin, viral infections</li> </ol><li>Mixed B- and T-cell hyperplasia</li><ol type="a"> <li>Cat-scratch disease
<blockquote style="color: blue; ">Cat-scratch disease: due to <i>Bartonella henselae</i></blockquote></li><ul> <li>(1) Granulomatous microabscesses in regional lymph nodes (e.g., axillary, cervical)</li><li>(2) Due to <i>Bartonella henselae</i></li><li>(3) Treatment is azithromycin.</li> </ul><li>Toxoplasmosis
<blockquote style="color: blue; ">Toxoplasmosis: mononucleosis type syndrome with painful cervical lymphadenopathy</blockquote></li><ul> <li>(1) Approximately 50% of the population has been infected with <i>Toxoplasma gondii</i>.</li><li>(2) Produces a mononucleosis-like syndrome with painful cervical lymphadenopathy</li> </ul><li>Tularemia</li><ul> <li>(1) Epidemiology</li><ul> <li>(a) <i>Francisella tularensis</i></li><li>(b) Gram-negative intracellular coccobacillus</li><li>(c) Zoonosis often seen in hunters, trappers</li><li>(d) Reservoirs</li><ul> <li>Rodents, deer, rabbits (90%)</li> </ul><li>(e) Transmission</li><ul> <li>Bites by <i>Dermacentor</i> ticks; skin contact with animal hide; aerosol</li> </ul> </ul><li>(2) Ulceroglandular type
<blockquote style="color: blue; ">Tularemia: zoonosis (rabbits); ulceroglandular type most common</blockquote></li><ul> <li>Most common presentation in the United States</li> </ul><ul> <li>(a) Localized papular lesion at the point of inoculation (bite) →</li><li>(b) Ulceration of the papule →</li><li>(c) Regional lymphadenitis (noncaseating granulomatous inflammation) →</li><ul> <li>Draining of lymph nodes</li> </ul><li>(d) Sepsis leading to dissemination throughout the body (e.g., spleen, liver)</li> </ul><li>(3) Treatment is gentamicin.</li> </ul> </ol><li>Sinus histiocytosis</li><ol type="a"> <li>Benign histiocytic response in lymph nodes draining a tumor</li><li>Favorable sign in the axillary nodes in breast cancer
<blockquote style="color: blue; ">Sinus histiocytosis axillary nodes: favorable sign in breast cancer</blockquote></li> </ol> </ol>
</div></html>
![[13.I.A.Locations of lymphoid tissue]]
<<tiddler [[13.I.A.Locations of lymphoid tissue]]>>
![[13.I.B.Lymphadenopathy (Fig. 13-3)]]
<<tiddler [[13.I.B.Lymphadenopathy (Fig. 13-3)]]>>
![[13.I.C.Types of reactive lymphadenitis]]
<<tiddler [[13.I.C.Types of reactive lymphadenitis]]>>
<html><a name="HC013006"></a> <br><a name="P013007"></a><div class="PA" style="color: black; "><ol type="1"> <li>Account for ∼60% of adult lymphomas</li><ul> <li>More than 80% are of B-cell origin and derive from the germinal follicle.
<blockquote style="color: blue; ">NHL: majority β-cell origin</blockquote></li> </ul><li>Second most common cancer in HIV</li><li>Approximately one third arise from extranodal sites.
<blockquote style="color: blue; ">Extranodal sites: stomach, CNS, Peyer's patch</blockquote></li><ul> <li>Examples-stomach (most common), Peyer's patches, central nervous system (CNS) (in HIV infections)</li> </ul><li>Childhood lymphomas</li><ol type="a"> <li>NHL accounts for 60% of cases.
<blockquote style="color: blue; ">NHL: most common malignant lymphoma adults/children</blockquote></li><ul> <li>Usually T-cell lymphoblastic lymphoma or Burkitt's lymphoma</li> </ul><li>Generally more aggressive than adult lymphomas</li> </ol><li>Risk factors for NHL</li><ol type="a"> <li>Viruses</li><ul> <li>(1) Epstein-Barr virus (EBV)
<blockquote style="color: blue; ">Epstein-Barr virus: Burkitt's lymphoma, CNS lymphoma</blockquote></li><ul> <li>(a) Burkitt's lymphoma</li><li>(b) Diffuse large B-cell lymphoma</li><li>(c) Primary CNS lymphoma</li><ul> <li>Associated with AIDS</li> </ul> </ul><li>(2) Human T-cell leukemia virus type I</li><ul> <li>Adult T-cell lymphoma or leukemia</li> </ul><li>(3) Hepatitis C virus</li><ul> <li>B-cell lymphoma</li> </ul> </ul><li><i>Helicobacter pylori</i></li><ul> <li>(1) Malignant lymphoma derives from mucosa-associated lymphoid tissue in the stomach.
<blockquote style="color: blue; "><i>H. pylori:</i> malignant lymphoma of stomach</blockquote></li><li>(2) Treatment of peptic ulcer disease caused by <i>H. pylori</i> reduces the risk for developing this lymphoma.</li> </ul><li>Autoimmune disease</li><ul> <li>(1) Sjögren's syndrome
<blockquote style="color: blue; ">Lymphoma in autoimmune disease: Sjögren's syndrome, Hoshimoto's thyroiditis</blockquote></li><ul> <li>Predisposes to salivary gland and gastrointestinal lymphomas</li> </ul><li>(2) Hashimoto's thyroiditis</li><ul> <li>Predisposes to thyroid malignant lymphoma</li> </ul> </ul><li>Immunodeficiency syndromes</li><ul> <li>(1) Chromosome instability syndromes (e.g., Bloom syndrome)</li><li>(2) AIDS</li> </ul><li>Immunosuppressive therapy</li><ul> <li>Recipients of organ or bone marrow transplants</li> </ul><li>High-dose radiation</li><ul> <li>Treatment of HL</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC013007"></a> <br><a name="P013008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Mutation produces a block at a specific stage in development of B or T cells.</li><li>Example-accumulation of small cleaved B cells in follicular lymphoma</li> </ol>
</div></html>
<html><a name="HC013008"></a><span>[[13-5|Figure 13-5]]</span> <br><span>[[Figs. 13-4|Figure 13-4]]</span> <br><span>[[Table 13-1|Table 13-1. COMMON TYPES OF B-CELL NON-HODGKIN'S LYMPHOMA]]</span> <br> <br> </html>
<html><a name="HC013009"></a> <br><a name="P013010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Precursor T-cell lymphoblastic leukemia/lymphoma</li><ol type="a"> <li>Precursor T-cell lymphoma accounts for 40% of childhood lymphomas.</li><ul> <li>(1) Primarily involves the anterior mediastinum and cervical nodes</li><li>(2) Bone marrow and central nervous system involvement is common.</li> </ul><li>Precursor T-cell lymphoblastic leukemia</li><ul> <li>Leukemic variant of this lymphoma</li> </ul> </ol><li>Mycosis fungoides and Sézary syndrome</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Both conditions involve neoplastic peripheral CD4 T helper (T<sub>H</sub>) cells.
<blockquote style="color: blue; ">Mycosis fungoides: neoplasm of CD4 T<sub>H</sub> cells; skin involvement</blockquote></li><li>(2) Usually involves adults 40 to 60 years of age</li> </ul><li>Mycosis fungoides</li><ul> <li>(1) Begins in skin (rash to plaque to nodular masses)</li><ul> <li>Progresses to lymph nodes, lung, liver, and spleen</li> </ul><li>(2) Groups of neoplastic cells in the epidermis are called Pautrier's microabscesses.</li> </ul><li>Sézary syndrome</li><ul> <li>(1) Mycosis fungoides with a leukemic phase
<blockquote style="color: blue; ">Sézary syndrome: mycosis fungoides in leukemic phase</blockquote></li><li>(2) Circulating cells are called Sézary cells (prominent nuclear cleft).</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC013010"></a> <br><a name="P013011"></a><div class="PA" style="color: black; "><ul> <li>Five-year survival rate is 63%; 10-year survival rate is 51%.</li> </ul>
</div></html>
![[13.II.A.Epidemiology]]
<<tiddler [[13.II.A.Epidemiology]]>>
![[13.II.B.Pathogenesis]]
<<tiddler [[13.II.B.Pathogenesis]]>>
![[13.II.C.B-cell lymphomas (Table 13-1 and Figs. 13-4 and 13-5)]]
<<tiddler [[13.II.C.B-cell lymphomas (Table 13-1 and Figs. 13-4 and 13-5)]]>>
![[13.II.D.T-cell lymphomas]]
<<tiddler [[13.II.D.T-cell lymphomas]]>>
![[13.II.E.NHL survival statistics]]
<<tiddler [[13.II.E.NHL survival statistics]]>>
<html><a name="HC013012"></a> <br><a name="P013014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Accounts for ∼40% of adult lymphomas</li><li>Age and sex</li><ol type="a"> <li>Slightly more common in men</li><ul> <li><i>Exception</i>-nodular sclerosing type is more common in women.
<blockquote style="color: blue; ">Nodular sclerosing HL: female dominant</blockquote></li> </ul><li>More common in adults than children</li><li>More common in whites than blacks</li> </ol><li>Bimodal age distribution</li><ol type="a"> <li>First large peak: 15 to 34 years old</li><li>Second smaller peak: >50 years old</li><li>Involves younger age bracket than NHL</li> </ol><li>Most common site of initial involvement is the neck region.</li><li>EBV association</li><ul> <li>EBV is identified in more than 50% of cases of mixed cellularity HL.
<blockquote style="color: blue; ">EBV: association with mixed cellularity HL</blockquote></li> </ul><li>Defects in cellular immunity</li><ul> <li>Defects in cutaneous anergy to common antigens (anergy)</li> </ul><li>Classification (<span>[[Table 13-2|Table 13-2. SOME TYPES OF HODGKIN'S LYMPHOMA (HL)]]</span>)</li><ol type="a"> <li>Lymphocyte predominant</li><li>Nodular sclerosing (most common type)
<blockquote style="color: blue; ">Nodular sclerosing HL: female dominant</blockquote></li><li>Mixed cellularity</li><li>Lymphocyte depletion (not discussed)</li> </ol> </ol>
</div></html>
<html><a name="HC013013"></a> <br><a name="P013015"></a><div class="PA" style="color: black; "><ol type="1"> <li>Possible genetic predisposition</li><li>Unknown factors (EBV, retrovirus) cause B and T cells to become neoplastic Reed-Sternberg cells.</li> </ol>
</div></html>
<html><a name="HC013014"></a> <br><a name="P013016"></a><div class="PA" style="color: black; "><ol type="1"> <li>Involves localized groups of nodes and has contiguous spread</li><ol type="a"> <li>Often involves cervical or supraclavicular nodes</li><li>Cut section has a bulging "fish-flesh" appearance</li> </ol><li>Reed-Sternberg (RS) cells</li><ol type="a"> <li>Neoplastic cell of HL
<blockquote style="color: blue; ">RS cell: neoplastic cell of HL; CD15+, CD30+</blockquote></li><ul> <li>(1) Transformed germinal center B cell (some cases)</li><li>(2) CD15 and CD30 positive</li> </ul><li>Classic RS cell</li><ul> <li>Two mirror image nuclei, each with an eosinophilic nucleolus surrounded by a clear halo (<span>[[Fig. 13-6|Figure 13-6]]</span>)</li> </ul><li>RS variants</li><ul> <li>(1) L and H variant</li><ul> <li>(a) Large, pale staining, multilobed cell ("popcorn cell")</li><li>(b) Present in lymphocyte predominant type</li> </ul><li>(2) Lacunar cells (<span>[[Fig. 13-7|Figure 13-7]]</span>)</li><ul> <li>(a) Pale cell with multilobed nucleus containing many small nucleoli</li><li>(b) Cell lies within a clear space in formalin-fixed tissue.</li><li>(c) Present in nodular sclerosing type</li> </ul><li>(3) Mononuclear variants</li><ul> <li>(a) Single nucleus with a prominent nucleolus</li><li>(b) Seen in mixed cellularity type</li> </ul> </ul> </ol><li>Diagnosis of HL</li><ol type="a"> <li>Presence of a classic RS cell is required
<blockquote style="color: blue; ">RS cell: required to make the diagnosis of HL</blockquote></li><li>Presence of RS variant cells in a background of reactive cells</li><ul> <li>Reactive cells include eosinophils, plasma cells, histiocytes.</li> </ul> </ol><li>Differences from NHL</li><ul> <li>Less commonly involves Waldeyer's ring, mesenteric nodes, and extranodal sites</li> </ul> </ol>
</div></html>
<html><a name="HC013015"></a> <br><a name="P013017"></a><div class="PA" style="color: black; "><ol type="1"> <li>Constitutional signs</li><ol type="a"> <li>Fever, unexplained weight loss, night sweats</li><li>Pruritus</li><li>Pel-Ebstein fever (uncommon variant of fever)
<blockquote style="color: blue; ">HL: Pel-Ebstein fever</blockquote></li><ul> <li>Alternating bouts of fever followed by remissions</li> </ul> </ol><li>Hematologic findings</li><ol type="a"> <li>Normocytic anemia</li><li>Painless enlargement of single groups of lymph nodes</li><ul> <li>Usually cervical, supraclavicular, or anterior mediastinal nodes
<blockquote style="color: blue; ">Prognosis: stage more important than type of HL</blockquote></li> </ul> </ol><li>Main factors determining prognosis</li><ol type="a"> <li>Clinical stage is more important than the type of HL.
<blockquote style="color: blue; ">Nodular sclerosing HL: anterior mediastinal mass + single group of nodes above diaphragm</blockquote></li><li>Majority have lymphadenopathy above the diaphragm (stages I and II).</li><ul> <li>Usually involves supraclavicular nodes and anterior mediastinal nodes</li> </ul> </ol><li>Increased risk for second malignancies</li><ol type="a"> <li>Acute myelogenous leukemia or NHL
<blockquote style="color: blue; ">Rx for HL: ↑ risk for second malignancies</blockquote></li><li>Complication of treatment with radiation and alkylating agents</li> </ol> </ol>
</div></html>
<html><a name="HC013016"></a> <br><a name="P013018"></a><div class="PA" style="color: black; "><ul> <li>Radiotherapy and chemotherapy depending on the stage</li> </ul>
</div></html>
<html><a name="HC013017"></a> <br><a name="P013019"></a><div class="PA" style="color: black; "><ul> <li>Five-year survival rate is 85%; 10-year survival rate is 80%.</li> </ul>
</div></html>
![[13.III.A.Epidemiology]]
<<tiddler [[13.III.A.Epidemiology]]>>
![[13.III.B.Pathogenesis]]
<<tiddler [[13.III.B.Pathogenesis]]>>
![[13.III.C.Pathologic findings]]
<<tiddler [[13.III.C.Pathologic findings]]>>
![[13.III.D.Clinical findings and prognosis]]
<<tiddler [[13.III.D.Clinical findings and prognosis]]>>
![[13.III.E.Treatment]]
<<tiddler [[13.III.E.Treatment]]>>
![[13.III.F.HL survival statistics]]
<<tiddler [[13.III.F.HL survival statistics]]>>
<html><a name="HC013019"></a> <br><a name="P013022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Langerhans histiocytes</li><ol type="a"> <li>CD1 positive</li><li>Contain Birbeck granules (tennis racket appearance; <span>[[Fig. 13-8|Figure 13-8]]</span>)
<blockquote style="color: blue; ">Histiocytes: CD1+ contain Birbeck granules</blockquote></li><ul> <li>Visible only with electron microscopy</li> </ul> </ol><li>Primarily occurs in children and young adults</li><li>Classification</li><ol type="a"> <li>Letterer-Siwe disease</li><li>Hand-Schüller-Christian disease</li><li>Eosinophilic granuloma</li> </ol> </ol>
</div></html>
<html><a name="HC013020"></a> <br><a name="P013023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Malignant histiocytosis</li><li>Epidemiology</li><ul> <li>Occurs in infants and children < 2 years old</li> </ul><li>Clinical findings
<blockquote style="color: blue; ">Malignant histiocytoses: skin involvement is common; lytic bone lesions</blockquote></li><ol type="a"> <li>Diffuse eczematous rash (<span>[[Fig. 13-9|Figure 13-9]]</span>)</li><li>Multiple organ involvement</li><li>Lytic lesions in the skull, pelvis, and long bones</li><li>Rapidly fatal</li> </ol> </ol>
</div></html>
<html><a name="HC013021"></a> <br><a name="P013024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Malignant histiocytosis</li><li>Epidemiology</li><ul> <li>Mainly affects children</li> </ul><li>Clinical findings</li><ol type="a"> <li>General</li><ul> <li>(1) Fever</li><li>(2) Localized rash on scalp and in ear canals</li> </ul><li>Classic triad due to infiltrative disease
<blockquote style="color: blue; ">HSC: lytic skull lesion, diabetes insipidus, exophthalmos</blockquote></li><ul> <li>(1) Lytic lesion in the skull</li><li>(2) Diabetes insipidus due to invasion of posterior pituitary</li><li>(3) Exophthalmos from infiltration of the orbit</li> </ul><li>Intermediate prognosis</li> </ol> </ol>
</div></html>
<html><a name="HC013022"></a> <br><a name="P013025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Benign histiocytosis</li><li>Epidemiology</li><ul> <li>Occurs in adolescents and young adults
<blockquote style="color: blue; ">Eosinophilic granuloma: benign histiocytosis; unifocal lytic lesions in bone</blockquote></li> </ul><li>Clinical findings</li><ol type="a"> <li>Unifocal lytic lesions in bone (skull, ribs, and femur)</li><li>Bone pain and pathologic fractures are common.</li> </ol> </ol>
</div></html>
![[13.IV.A.Epidemiology]]
<<tiddler [[13.IV.A.Epidemiology]]>>
![[13.IV.B.Letterer-Siwe disease]]
<<tiddler [[13.IV.B.Letterer-Siwe disease]]>>
![[13.IV.C.Hand-Schüller-Christian (HSC) disease]]
<<tiddler [[13.IV.C.Hand-Schüller-Christian (HSC) disease]]>>
![[13.IV.D.Eosinophilic granulomas]]
<<tiddler [[13.IV.D.Eosinophilic granulomas]]>>
<html><a name="HC013024"></a> <br><a name="P013028"></a><div class="PA" style="color: black; "><ol type="1"> <li>Presentation</li><ol type="a"> <li>Localized-urticaria pigmentosum, solitary mastocytoma</li><li>Systemic-systemic mastocytosis
<blockquote style="color: blue; ">Mast cell disease: pruritus, swelling, hyperpigmentation</blockquote></li> </ol><li>Signs and symptoms relate to mast cell release of histamine.</li><ul> <li>Pruritus and swelling of tissue</li> </ul> </ol>
</div></html>
<html><a name="HC013025"></a> <br><a name="P013029"></a><div class="PA" style="color: black; "><ol type="1"> <li>Skin lesions</li><ol type="a"> <li>Multiple oval, red-brown, nonscaling macules (flat lesions) or papules (<span>[[Fig. 13-10|Figure 13-10]]</span>)</li><li>Scratching results in erythematous swelling of the lesions and pruritus.</li><ul> <li>Called Darier's sign</li> </ul><li>Dermatographism</li><ul> <li>Dermal edema occurs when apparently normal skin is stroked with a pointed object.
<blockquote style="color: blue; ">UP: dermatographism; lesions remain hyperpigmented</blockquote></li> </ul><li>Lesions remain hyperpigmented when they regress.</li><li>Skin biopsy</li><ul> <li>(1) Mast cells have metachromatic granules.
<blockquote style="color: blue; ">Mast cells: metachromatic granules</blockquote></li><li>(2) Granules stain positive with toluidine blue and Giemsa stain.</li> </ul> </ol><li>Pruritus and flushing may be triggered by foods, alcohol, drugs (e.g., codeine).</li> </ol>
</div></html>
![[13.V.A.Overview]]
<<tiddler [[13.V.A.Overview]]>>
![[13.V.B.Urticaria pigmentosum (UP)]]
<<tiddler [[13.V.B.Urticaria pigmentosum (UP)]]>>
<html><a name="HC013027"></a> <br><a name="P013030"></a><div class="PA" style="color: black; "><ol type="1"> <li>Monoclonal B-cell disorders</li><ol type="a"> <li>Increase in a single immunoglobulin</li><li>Increase in the corresponding light chain</li> </ol><li>Immunoglobulin is detected as a monoclonal spike (M component) on serum protein electrophoresis (<span>[[Fig. 13-11|Figure 13-11]]</span>).
<blockquote style="color: blue; ">Plasma cell dyscrasia: monoclonal spike; usually IgG</blockquote></li><li>Clinical significance of M components</li><ol type="a"> <li>Most commonly due to an increase in IgG</li><ul> <li>Other plasma cell clones are suppressed.</li> </ul><li>Bence Jones (BJ) protein</li><ul> <li>(1) Refers to κ or λ light chains excreted in urine
<blockquote style="color: blue; ">BJ protein: light chains in the urine</blockquote></li><li>(2) Associated with a plasma cell malignancy and Waldenström's macroglobulinemia</li> </ul><li>Immunoelectrophoresis or immunofixation</li><ul> <li>These techniques identify the immunoglobulin and light chain in serum and light chains in urine.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC013028"></a> <br><a name="P013031"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>More common in blacks than in whites</li><li>Rare under 40 years of age
<blockquote style="color: blue; ">Myeloma: rare <40 years of age</blockquote></li><li>Peak incidence in 50 to 60 year olds</li><li>Accounts for 10% of all hematologic malignancies</li><li>Increased risk with radiation or benzene exposure</li><li>M-spike occurs in 80% to 90% of cases.</li><ul> <li>(1) Usually IgG κ light chain followed by IgA and pure light chain myeloma</li><li>(2) BJ represents excess light chains in urine.</li><li>(3) Urine BJ protein is positive in 60% to 80% of cases.</li> </ul> </ol><li>Pathophysiology</li><ol type="a"> <li>Chromosome abnormalities (deletions, translocations)
<blockquote style="color: blue; ">Myeloma: normal plasma cell → MGUS → myeloma</blockquote></li><li>Possible evolution from normal plasma cells → monoclonal gammopathy of undetermined significance (MGUS) → multiple myeloma</li> </ol><li>Pathologic findings</li><ol type="a"> <li>Sheets of malignant plasma cells in a bone marrow aspirate/biopsy (<span>[[Fig. 13-12|Figure 13-12]]</span>)</li><li>Plasma cells account for >10% of cells in the aspirate.</li> </ol><li>Skeletal system findings</li><ol type="a"> <li>Bone pain
<blockquote style="color: blue; ">Bone findings in myeloma: lytic lesions, pathologic fractures, hypercalcemia</blockquote></li><ul> <li>(1) Due to "punched out" lytic lesions (<span>[[Fig. 13-13|Figure 13-13]]</span>)</li><ul> <li>(a) Myeloma cells produce an inhibitor of osteoblast differentiation</li><li>(b) Myeloma cells release interleukin 1 (osteoclast activating factor)</li> </ul><li>(2) Vertebra is the most common site.</li><li>(3) Other sites include ribs, skull, pelvis.</li><li>(4) Commonly presents with pathologic fractures</li><ul> <li>Particularly rib lesions</li> </ul> </ul><li>Hypercalcemia (25% of cases)</li> </ol><li>Renal findings</li><ol type="a"> <li>Renal failure (30-50% of cases)</li><li>Myeloma kidney has different presentations.</li><ul> <li>(1) Proteinaceous tubular casts</li><ul> <li>(a) Composed of BJ protein
<blockquote style="color: blue; ">BJ renal disease in myeloma: proteinaceous casts with multinucleated giant cell reaction</blockquote></li><li>(b) BJ protein damages tubular epithelium</li><li>(c) Intratubular multinucleated giant cell reaction</li> </ul><li>(2) Nephrocalcinosis</li><ul> <li>(a) Metastatic calcification of tubular basement membranes in the collecting ducts (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li><li>(b) Common cause of acute renal failure in multiple myeloma</li> </ul><li>(3) Metastatic disease to interstitial tissue</li><li>(4) Primary amyloidosis (10% of cases)</li><ul> <li>(a) Light chains are converted into amyloid (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>).</li><li>(b) Produces a nephrotic syndrome</li> </ul> </ul> </ol><li>Hematologic findings</li><ol type="a"> <li>Normocytic anemia with rouleaux (see Fig. 2-17)</li><li>Increased erythrocyte sedimentation rate</li><li>Prolonged bleeding time</li><ul> <li>Due to a defect in platelet aggregation</li> </ul> </ol><li>Radiculopathy from bone compression and vertebral fractures</li><li>Recurrent infection is a common cause of death.
<blockquote style="color: blue; ">Myeloma: sepsis and renal failure common causes of death</blockquote></li><ul> <li>Sepsis due to <i>Haemophilus influenzae</i>, <i>Streptococcus pneumoniae</i></li> </ul><li>Treatment</li><ol type="a"> <li>High-dose chemotherapy</li><li>Autologous stem cell transplantation</li> </ol><li>Prognosis</li><ul> <li>Median survival after diagnosis is 3 years.
<blockquote style="color: blue; ">MGUS: most common monoclonal gammopathy</blockquote></li> </ul> </ol>
</div></html>
<html><a name="HC013029"></a><span>[[Table 13-3|Table 13-3. ADDITIONAL PLASMA CELL DYSCRASIAS]]</span> <br> <br></html>
![[13.VI.A.Overview]]
<<tiddler [[13.VI.A.Overview]]>>
![[13.VI.B.Multiple myeloma]]
<<tiddler [[13.VI.B.Multiple myeloma]]>>
![[13.VI.C.Other plasma cell dyscrasias (Table 13-3)]]
<<tiddler [[13.VI.C.Other plasma cell dyscrasias (Table 13-3)]]>>
<html><a name="HC013031"></a> <br><a name="P013036"></a><div class="PA" style="color: black; "><ol type="1"> <li>Red pulp
<blockquote style="color: blue; ">Red pulp: fixed macrophages</blockquote></li><ul> <li>Contains the cords of Billroth with fixed macrophages and sinusoids</li> </ul><li>White pulp
<blockquote style="color: blue; ">White pulp: B and T cells</blockquote></li><ul> <li>Contains B and T cells</li> </ul><li>Important functions of the spleen</li><ol type="a"> <li>Blood filtration; macrophages remove:</li><ul> <li>(1) Hematopoietic elements (e.g., old red blood cells)</li><li>(2) Intraerythrocytic parasites (e.g., malaria)</li><li>(3) Encapsulated bacteria</li><ul> <li>Examples-<i>Streptococcus pneumoniae</i></li> </ul> </ul><li>Antigen trapping and processing in macrophages</li><li>Reservoir for one third of the peripheral blood platelet pool</li><li>Site for extramedullary hematopoiesis (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li> </ol> </ol>
</div></html>
<html><a name="HC013032"></a> <br><a name="P013037"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes of splenomegaly
<blockquote style="color: blue; ">Malaria: most common cause splenomegaly in developing countries</blockquote></li><ol type="a"> <li>Autoimmune disorders</li><ul> <li>Examples-SLE, immune thrombocytopenia, and anemia</li> </ul><li>Infectious mononucleosis</li><ul> <li>Due to antigenic stimulation of T cells</li> </ul><li>Parasitic infections</li><ul> <li>Malaria is the most common cause of splenomegaly in developing countries.</li> </ul><li>Primary and reactive (secondary) amyloidosis</li><li>Lysosomal storage diseases</li><ul> <li>(1) Gaucher's disease
<blockquote style="color: blue; ">Gaucher's disease: ↓ glucocerebrosidase, ↑ glucocerebroside</blockquote></li><ul> <li>(a) Deficiency of glucocerebrosidase</li><ul> <li>Lysosomal accumulation of glucocerebrosides</li> </ul><li>(b) Macrophages have a fibrillary appearance (<span>[[Fig. 13-14|Figure 13-14]]</span>).</li> </ul><li>(2) Niemann-Pick disease
<blockquote style="color: blue; ">Niemann-Pick: ↓ sphingomyelinase, ↑ sphingomyelin</blockquote></li><ul> <li>(a) Deficiency of sphingomyelinase</li><ul> <li>Lysosomal accumulation of sphingomyelin</li> </ul><li>(b) Macrophages have soap bubble appearance (<span>[[Fig. 13-15|Figure 13-15]]</span>).</li> </ul> </ul><li>Acute and chronic leukemias</li><li>Hereditary spherocytosis</li><li>Portal hypertension in cirrhosis</li><li>Chronic myeloproliferative diseases</li><ul> <li>Polycythemia vera, myelofibrosis and myeloid metaplasia, essential thrombocythemia</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Left upper quadrant pain
<blockquote style="color: blue; ">Massive splenomegaly: infarctions common with pain, friction rub, and leftsided pleural effusion</blockquote></li><ul> <li>May be associated with splenic infarctions causing friction rubs and a left-sided pleural effusion</li> </ul><li>Hypersplenism (see later)</li> </ol> </ol>
</div></html>
<html><a name="HC013033"></a> <br><a name="P013038"></a><div class="PA" style="color: black; "><ol type="1"> <li>Gross findings</li><ul> <li>Spleen is often surfaced by a thickened ("sugar-coated") capsule from perisplenitis.
<blockquote style="color: blue; ">Splenomegaly in cirrhosis: "sugar-coated" spleen</blockquote></li> </ul><li>Microscopic findings</li><ul> <li>Calcium and iron concretions called Gamna-Gandy bodies are present in collagen.</li> </ul> </ol>
</div></html>
<html><a name="HC013034"></a> <br><a name="P013039"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Hypersplenism: destruction of hematopoietic cells producing cytopenias</blockquote>
<ol type="1"> <li>Definition</li><ol type="a"> <li>Exaggeration of normal splenic function</li><li>RBCs, WBCs, and platelets, either singly or in combination, are sequestered and destroyed.</li> </ol><li>Portal hypertension associated with cirrhosis is the most common cause.</li><li>Clinical findings</li><ol type="a"> <li>Splenomegaly</li><li>Peripheral blood cytopenias</li><ul> <li>Anemia, thrombocytopenia, neutropenia alone or in combination</li> </ul><li>Compensatory reactive bone marrow hyperplasia</li><ul> <li>Attempt by the marrow to replace lost cells</li> </ul><li>Correction of cytopenias with splenectomy</li> </ol> </ol>
</div></html>
<html><a name="HC013035"></a> <br><a name="P013040"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Splenic dysfunction: ↑ risk for <i>Streptococcus pneumoniae</i> sepsis</blockquote>
<ol type="1"> <li>Splenic dysfunction</li><ol type="a"> <li>Presence of Howell-Jolly bodies (nuclear remnants) in peripheral blood RBCs</li><li>Predisposition to infections by encapsulated pathogens</li><ul> <li>(1) Infections include septicemia, peritonitis, osteomyelitis.</li><li>(2) Pathogens include:</li><ul> <li><i>Streptococcus pneumoniae</i>, <i>Haemophilus influenzae</i>, <i>Salmonella</i>, <i>Neisseria meningitidis</i></li> </ul><li>(3) Mechanisms
<blockquote style="color: blue; ">Mechanisms: ↓ IgM, ↓ tuftsin, ↓ splenic macrophages</blockquote></li><ul> <li>(a) Concentration of IgM drops leading to a decrease in complement system activation</li><ul> <li>The spleen is a site for IgM synthesis.</li> </ul><li>(b) Macrophages are <i>not</i> present to phagocytose the opsonized encapsulated pathogens.</li><li>(c) Loss of tuftsin, which is normally synthesized in the spleen</li><ul> <li>Tuftsin activates receptors on macrophages to increase their phagocytic activity.</li> </ul> </ul><li>(4) Pathogens commonly involved</li><ul> <li>(a) <i>Streptococcus pneumoniae</i></li><li>(b) Other pathogens include <i>Haemophilus influenzae</i> and <i>Salmonella paratyphi</i> (osteomyelitis in sickle cell disease).</li><ul> <li>Immunization helps prevent infectious complications.</li> </ul> </ul> </ul> </ol><li>Splenectomy</li><ol type="a"> <li>Increases the risk for infections (see earlier)</li><li>Hematologic findings</li><ul> <li>(1) Nucleated RBCs</li><li>(2) Howell-Jolly bodies</li><li>(3) Target cells (excess membrane cannot be removed)</li><li>(4) Thrombocytosis</li><ul> <li>Platelets normally sequestered in the spleen are now circulating.</li> </ul> </ul> </ol> </ol>
</div></html>
![[13.VII.A.Clinical anatomy and physiology]]
<<tiddler [[13.VII.A.Clinical anatomy and physiology]]>>
![[13.VII.B.Splenomegaly]]
<<tiddler [[13.VII.B.Splenomegaly]]>>
![[13.VII.C.Portal hypertension in cirrhosis]]
<<tiddler [[13.VII.C.Portal hypertension in cirrhosis]]>>
![[13.VII.D.Hypersplenism]]
<<tiddler [[13.VII.D.Hypersplenism]]>>
![[13.VII.E.Splenic dysfunction and splenectomy]]
<<tiddler [[13.VII.E.Splenic dysfunction and splenectomy]]>>
<html><a name="HC014002"></a> <br><a name="P014002"></a><div class="PA" style="color: black; "><ul> <li>Small blood vessels include capillaries, venules, arterioles.
<blockquote style="color: blue; ">Heparin-like molecules: enhance ATIII activity</blockquote></li><ol type="1"> <li>Heparin-like molecules</li><ol type="a"> <li>Enhance antithrombin III (ATIII) activity
<blockquote style="color: blue; ">ATIII: neutralizes activated serine protease coagulation factors</blockquote></li><li>Neutralize activated serine protease coagulation factors</li><ul> <li>Factors XII, XI, IX, and X; thrombin (activated prothrombin)</li> </ul> </ol><li>Prostaglandin (PG) I<sub>2</sub> (prostacyclin)</li><ol type="a"> <li>Synthesized by intact endothelial cells</li><li>PGH<sub>2</sub> is converted by prostacyclin synthase to PGI<sub>2</sub>.
<blockquote style="color: blue; ">PGI<sub>2</sub>: vasodilator, inhibits platelet aggregation</blockquote></li><li>Vasodilator; inhibits platelet aggregation</li><li>Aspirin does <i>not</i> inhibit synthesis of PGI<sub>2</sub> by endothelial cells.</li> </ol><li>Proteins C and S</li><ol type="a"> <li>Vitamin K-dependent factors</li><li>Inactivate factors V and VIII</li><li>Enhance fibrinolysis</li> </ol><li>Tissue plasminogen activator (tPA)
<blockquote style="color: blue; ">Proteins C and S: inactivate factors V and VIII, enhance fibrinolysis</blockquote></li><ol type="a"> <li>Synthesized by endothelial cells</li><li>Activates plasminogen to release plasmin</li><li>Plasmin degrades coagulation factors and lyses fibrin clots (thrombi).
<blockquote style="color: blue; ">tPA: activates plasminogen to release plasmin</blockquote></li> </ol> </ol> </ul>
</div></html>
<html><a name="HC014003"></a> <br><a name="PB014001"></a><div class="BB" style="color: rgb(47, 79, 79); ">Factor VIII:c is synthesized by the liver and reticuloendothelial tissues. When VIII:c is activated by thrombin, it dissociates from the VIII:vWF complex and performs its procoagulant function in the intrinsic coagulation cascade system.</div><a name="P014003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Thromboxane A<sub>2</sub> (TXA<sub>2</sub>)</li><ol type="a"> <li>Synthesized by platelets</li><ul> <li>(1) PGH<sub>2</sub> is converted into TXA<sub>2</sub> by thromboxane synthase.</li><li>(2) Aspirin <i>irreversibly</i> inhibits platelet cyclooxygenase.</li><ul> <li>Prevents formation of PGH<sub>2</sub>, the precursor for TXA<sub>2</sub></li> </ul><li>(3) Other NSAIDs <i>reversibly</i> inhibit platelet cyclooxygenase.</li><li>(4) Prostacyclin synthase in endothelial cells is minimally affected by NSAIDs.</li> </ul><li>Functions of TXA<sub>2</sub> in hemostasis
<blockquote style="color: blue; ">TXA<sub>2</sub>: vasoconstrictor; enhances platelet aggregation</blockquote></li><ul> <li>Vasoconstrictor, enhances platelet aggregation</li> </ul> </ol><li>Von Willebrand factor (vWF)
<blockquote style="color: blue; ">vWF: platelet adhesion molecule; synthesized in Weibel-Palade bodies in endothelial cells</blockquote></li><ol type="a"> <li>Synthesized by endothelial cells and megakaryocytes</li><ul> <li>(1) Synthesized in Weibel-Palade bodies in endothelial cells</li><li>(2) Platelets carry vWF in their α-granules.</li> </ul><li>Functions of vWF</li><ul> <li>(1) Platelet adhesion molecule</li><ul> <li>(a) Binds platelets to exposed collagen
<blockquote style="color: blue; ">Factor VIII:c: synthesized in the liver</blockquote></li><li>(b) Platelets have glycoprotein (Gp) Ib receptors for vWF.</li> </ul><li>(2) Complexes with factor VIII coagulant activity (factor VIII:c) in the circulation
<blockquote style="color: blue; ">vWF: ↓ vWF causes ↓ VIII:c</blockquote></li><ul> <li>(a) Factor VIII:c is synthesized by the liver and other sites.</li><li>(b) VIII:vWF complexes with VIII:c in the circulation.
<blockquote style="color: blue; ">vWF: platelet adhesion; prevents degradation of VIII:c in plasma</blockquote></li><ul> <li>Prevents degradation of factor VIII:c</li> </ul><li>(c) Decrease in vWF secondarily decreases VIII:c activity.</li> </ul> </ul> </ol><li>Tissue thromboplastin (factor III)</li><ol type="a"> <li>Noncirculating ubiquitous substance</li><ul> <li>Released from injured tissue</li> </ul><li>Activates factor VII in the extrinsic coagulation system
<blockquote style="color: blue; ">Tissue thromboplastin: activates factor VII in extrinsic coagulation system</blockquote></li> </ol><li>Extrinsic and intrinsic coagulation systems (see later)</li> </ol>
</div></html>
<html><a name="HC014004"></a> <br><a name="P014004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Derivation</li><ol type="a"> <li>Cytoplasmic fragmentation of megakaryocytes</li><li>Approximately 1000 to 3000 platelets are produced per megakaryocyte.</li> </ol><li>Locations</li><ol type="a"> <li>Peripheral blood (live for ∼9-10 days)</li><li>Approximately one third of the total platelet pool is stored in the spleen.</li> </ol><li>Platelet receptors
<blockquote style="color: blue; ">Platelet receptors: GpIb (binds to vWF); GpIIb-IIIa (binds to fibrinogen)</blockquote></li><ol type="a"> <li>Glycoprotein (Gp) receptors for vWF are designated GpIb.</li><li>Glycoprotein receptors for fibrinogen are designated GpIIb-IIIa.</li><ul> <li>(1) Ticlopidine and clopidogrel</li><ul> <li>(a) Inhibit adenosine diphosphate (ADP)-induced expression of platelet GpIIb-IIIa receptors</li><li>(b) Prevents fibrinogen binding and platelet aggregation</li> </ul><li>(2) Abciximab</li><ul> <li>Monoclonal antibody that is directed against the GpIIb-IIIa receptor
<blockquote style="color: blue; ">Ticlopidine, clopidogrel, abciximab: interfere with GpIIb-IIIa receptor function</blockquote></li> </ul> </ul> </ol><li>Platelet factor 3 (PF3)</li><ol type="a"> <li>Located on the platelet membrane</li><li>Phospholipid substrate required for the clotting sequence</li> </ol><li>Platelet structure</li><ol type="a"> <li>Contractile element</li><ul> <li>(1) Called thrombosthenin</li><li>(2) Helps in clot retraction</li> </ul><li>Dense bodies contain:</li><ul> <li>(1) ADP, an aggregating agent</li><li>(2) Calcium, a binding agent for vitamin K-dependent factors</li> </ul><li>α-Granules contain:</li><ul> <li>(1) vWF, fibrinogen
<blockquote style="color: blue; ">Important platelet storage proteins: ADP, vWF, fibrinogen</blockquote></li><li>(2) Platelet factor 4 (PF4)</li><ul> <li>Heparin neutralizing factor</li> </ul> </ul> </ol><li>Platelet function
<blockquote style="color: blue; ">Platelet function: stabilizes intercellular adherens junctions in venular endothelial cells</blockquote></li><ol type="a"> <li>Fill gaps between endothelial cells in small vessels</li><ul> <li>(1) Prevents leakage of RBCs into the interstitium</li><li>(2) Platelet dysfunction causes leakage of RBCs, producing petechiae.</li> </ul><li>Formation of the hemostatic plug in small vessel injury</li><li>Platelet-derived growth factor stimulates smooth muscle hyperplasia.</li><ul> <li>Important in the pathogenesis of atherosclerosis</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC014005"></a><span>[[Fig. 14-1|Figure 14-1]]</span> <br> <br><a name="PB014002"></a><div class="BB" style="color: rgb(47, 79, 79); ">When blood is drawn into a clot tube (no anticoagulant is added), a fibrin clot is formed. When the tube is spun down in a centrifuge, the supranate is called serum, which, unlike plasma, is missing fibrinogen, prothrombin (II), factor V, and factor VIII.</div><a name="P014005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Coagulation cascade</li><ol type="a"> <li>Extrinsic system (factor VII)</li><li>Intrinsic system (factors XII, XI, IX, VIII)</li> </ol><li>Extrinsic system
<blockquote style="color: blue; ">Extrinsic system: factor VII</blockquote></li><ol type="a"> <li>Factor VII is activated (factor VIIa) by tissue thromboplastin.</li><li>Factor VIIa activates factor X in the final common pathway.</li> </ol><li>Intrinsic system
<blockquote style="color: blue; ">Intrinsic system: factors XII, XI, IX, VIII</blockquote></li><ol type="a"> <li>Factor XII (Hageman factor) is activated by:</li><ul> <li>(1) Exposed subendothelial collagen</li><li>(2) High-molecular-weight kininogen (HMWK)</li> </ul><li>Functions of factor XIIa</li><ul> <li>(1) Activates factor XI</li><li>(2) Activates plasminogen (produces plasmin)
<blockquote style="color: blue; ">Factor XIIa: activates the kininogen system</blockquote></li><li>(3) Activates the kininogen system (produces kallikrein and bradykinin)</li> </ul><li>Factor XIa activates factor IX to form factor IXa.</li><ul> <li>(1) Four-component complex is formed (IXa, VIII, PF3, calcium).</li><li>(2) Complex activates factor X in the final common pathway.</li><li>(3) Calcium binds factor IXa, a vitamin K-dependent coagulation factor.</li> </ul> </ol><li>Final common pathway
<blockquote style="color: blue; ">Final common pathway: factors X, V, II, I</blockquote></li><ol type="a"> <li>Includes factors X, V, prothrombin (II), and fibrinogen (I)</li><li>Prothrombin complex</li><ul> <li>(1) Four-component system consisting of factor Xa, factor V, PF3, and calcium</li><li>(2) Calcium binds factor Xa, a vitamin K-dependent coagulation factor.</li><li>(3) Complex cleaves prothrombin into thrombin (enzyme).</li> </ul><li>Functions of thrombin</li><ul> <li>(1) Acts on fibrinogen to produce fibrin monomers plus fibrinopeptides A and B</li><li>(2) Activates fibrin stabilizing factor XIII</li><ul> <li>(a) Factor XIIIa converts soluble fibrin monomers to insoluble fibrin.</li><li>(b) Enhances protein-protein cross-linking to strengthen the fibrin clot
<blockquote style="color: blue; ">Factor XIII: cross-links insoluble fibrin monomers</blockquote></li><ul> <li>Cross-links are detected in <span style="font-variant:small-caps;">d</span>-dimer assay.</li> </ul> </ul><li>(3) Activates VIII:c in the intrinsic system</li> </ul> </ol><li>Vitamin K-dependent factors
<blockquote style="color: blue; ">Vitamin K-dependent factors: procoagulants II, VII, IX, X; anticoagulants protein C and S</blockquote></li><ol type="a"> <li>Factors II, VII, IX, X, protein C, and protein S</li><li>Synthesized in the liver as nonfunctional precursor proteins</li><li>Function of vitamin K</li><ul> <li>(1) Vitamin K is activated in the liver by epoxide reductase.</li><ul> <li>Majority of vitamin K is synthesized by colonic bacteria.
<blockquote style="color: blue; ">Vitamin K: liver activated by epoxide reductase</blockquote></li> </ul><li>(2) Activated vitamin K γ-carboxylates each factor.</li><ul> <li>Carboxylated factors can bind to calcium and PF3 in the cascade sequence.
<blockquote style="color: blue; ">Calcium: binds γ-carboxylated vitamin K-dependent factors</blockquote></li> </ul> </ul> </ol><li>Certain coagulation factors are consumed in the formation of a fibrin clot.</li><ul> <li>Consumed factors are fibrinogen (I), factor V, factor VIII, and prothrombin (II)</li> </ul> </ol>
</div></html>
<html><a name="HC014006"></a> <br><a name="P014006"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Factors consumed in a clot: I, II, V, VIII; serum</blockquote>
<ol type="1"> <li>Activation</li><ol type="a"> <li>tPA activates plasminogen to release the enzyme plasmin.</li><ul> <li>Alteplase and reteplase are recombinant forms of tPA used in thrombolytic therapy.</li> </ul><li>Other activators of plasminogen
<blockquote style="color: blue; ">Plasminogen activators: tPA, streptokinase, urokinase</blockquote></li><ul> <li>(1) Factor XIIa</li><li>(2) Streptokinase</li><ul> <li>Derived from streptococci</li> </ul><li>(3) Anistreplase</li><ul> <li>Complex of streptokinase and plasminogen</li> </ul><li>(4) Urokinase (derived from human urine)
<blockquote style="color: blue; ">Aminocaproic acid: inhibits plasminogen</blockquote></li> </ul><li>Aminocaproic acid</li><ul> <li>Competitively blocks plasminogen activation, thereby inhibiting fibrinolysis</li> </ul> </ol><li>Functions of plasmin</li><ol type="a"> <li>Cleaves insoluble fibrin monomers and fibrinogen into fibrin(ogen) degradation products (FDPs)</li><ul> <li>Fragments of cross-linked insoluble fibrin monomers are called <span style="font-variant:small-caps;">d</span>-dimers.
<blockquote style="color: blue; "><span style="font-variant:small-caps;">d</span>-Dimers: cross-linked fibrin monomers</blockquote></li> </ul><li>Degrades factors V, VIII, and fibrinogen</li><li>α<sub>2</sub>-Antiplasmin inactivates plasmin.</li><ul> <li>Synthesized in the liver</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC014007"></a><span>[[Fig. 14-2|Figure 14-2]]</span> <br> <br><a name="P014007"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sequence involves vascular, platelet, coagulation, and fibrinolytic phases.</li><li>Vascular phase</li><ol type="a"> <li>Transient vasoconstriction occurs directly after injury.</li><li>Factor VII (extrinsic system) is locally activated by tissue thromboplastin.</li><li>Exposed collagen activates factor XII (intrinsic system).</li><li>Thrombin produced changes fibrinogen holding platelets together into fibrin at the end of the platelet phase.</li> </ol><li>Platelet phase
<blockquote style="color: blue; ">Platelet sequence in hemostasis: adhesion, release reaction, synthesis TXA<sub>2</sub>, temporary plug</blockquote></li><ol type="a"> <li>Platelet adhesion</li><ul> <li>Platelet GpIb receptors adhere to exposed vWF in damaged endothelial cells.</li> </ul><li>Platelet release reaction</li><ul> <li>(1) Release of ADP</li><li>(2) Produces conformational changes in GpIIb-IIIa receptor</li> </ul><li>Platelet synthesis and release of TXA<sub>2</sub>
<blockquote style="color: blue; ">TXA<sub>2</sub>: enhances fibrinogen attachment to GpIIb-IIIa receptors</blockquote></li><ul> <li>(1) TXA<sub>2</sub> is a vasoconstrictor, which reduces blood flow.</li><li>(2) TXA<sub>2</sub> is a platelet aggregator.</li><ul> <li>Enhances fibrinogen attachment to GpIIb-IIIa receptors</li> </ul> </ul><li>Temporary platelet plug stops bleeding.
<blockquote style="color: blue; ">Temporary platelet plug: held together by fibrinogen</blockquote></li><ul> <li>(1) Unstable plug that can easily be dislodged</li><li>(2) Only held together by fibrinogen (no cross-links)</li><li>(3) Correlates with the end of the bleeding time (BT)</li> </ul> </ol><li>Coagulation phase</li><ol type="a"> <li>Fibrinogen attached to GpIIb-IIIa receptors is converted by thrombin (see above) to insoluble fibrin monomers (cross-linked).</li><li>Stable platelet plug is formed.
<blockquote style="color: blue; ">Stable platelet plug: held together by fibrin</blockquote></li><ul> <li>Held together by fibrin, <i>not</i> fibrinogen</li> </ul> </ol><li>Fibrinolytic phase</li><ol type="a"> <li>Plasmin cleaves the insoluble fibrin monomers holding the platelet plug together.</li><li>Blood flow is eventually re-established.</li> </ol> </ol>
</div></html>
<html><a name="HC014008"></a> <br><a name="P014008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Platelet count</li><ol type="a"> <li>Normal count is 150,000 to 400,000 cells/mm<sup>3</sup>.</li><li>A normal count does <i>not</i> guarantee normal platelet function.</li> </ol><li>Bleeding time</li><ol type="a"> <li>Evaluates platelet function up to the formation of the temporary platelet plug
<blockquote style="color: blue; ">BT: test of platelet function to formation of temporary plug</blockquote></li><ul> <li>(1) Normal reference interval is 2 to 7 minutes.</li><li>(2) Many laboratories have discontinued the BT.</li> </ul><li>Disorders causing a prolonged BT are listed in <span>[[Table 14-1|Table 14-1. CAUSES OF PROLONGED BLEEDING TIME]]</span>.</li> </ol><li>Platelet aggregation test</li><ol type="a"> <li>Evaluates platelet aggregation in response to aggregating reagents</li><li>Aggregating agents include ADP, epinephrine, collagen, and ristocetin.</li> </ol><li>Tests for vWF</li><ol type="a"> <li>Ristocetin cofactor assay
<blockquote style="color: blue; ">Ristocetin cofactor assay: test of vWF function</blockquote></li><ul> <li>(1) Evaluates vWF function</li><li>(2) Abnormal assay</li><ul> <li>(a) Classic von Willebrand disease (deficiency of vWF)</li><li>(b) Bernard-Soulier disease (absent GpIb receptor)</li> </ul> </ul><li>vWF antigen assay</li><ul> <li>(1) Measures the quantity of vWF regardless of function</li><li>(2) Decreased in classic von Willebrand disease</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC014009"></a><span>[[Fig. 14-3|Figure 14-3]]</span> <br> <br><a name="PB014003"></a><div class="BB" style="color: rgb(47, 79, 79); ">Whether the patient is anticoagulated with heparin or warfarin, both the PT and PTT are prolonged, because both inhibit factors in the final common pathway. Experience has shown that the PT performs better in monitoring warfarin, while the PTT performs better in monitoring heparin.</div><a name="P014009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Prothrombin time (PT)</li><ol type="a"> <li>Evaluates the extrinsic system down to formation of the fibrin clot</li><ul> <li>Factors evaluated include VII, X, V, II, and I.
<blockquote style="color: blue; ">PT: evaluates factors VII, X, V, II, and I</blockquote></li> </ul><li>Normal reference interval for PT is 11 to 15 seconds.</li><ul> <li>Only prolonged when a factor level is 30% to 40% of normal</li> </ul><li>International normalized ratio (INR)
<blockquote style="color: blue; ">INR: standardizes PT for warfarin therapy</blockquote></li><ul> <li>(1) Standardizes the PT for use in warfarin therapy</li><li>(2) Results are the same regardless of the reagents used to perform the test.</li><li>(3) Usual range for INR is 2 to 3.</li> </ul><li>Uses of PT</li><ul> <li>(1) Follow patients who are taking warfarin for anticoagulation</li><li>(2) Evaluate liver synthetic function</li><ul> <li>Increased PT indicates severe liver dysfunction.</li> </ul><li>(3) Detect factor VII deficiency</li> </ul> </ol><li>Partial thromboplastin time (PTT)</li><ol type="a"> <li>Evaluates the intrinsic system down to formation of a fibrin clot</li><ul> <li>Factors evaluated include XII, XI, IX, VIII, X, V, II, and I.
<blockquote style="color: blue; ">PTT: evaluates factors XII, XI, IX, VIII, X, V, II, I</blockquote></li> </ul><li>Normal reference interval for PTT is 25 to 40 seconds.</li><ul> <li>Only prolonged when a factor level is 30% to 40% of normal</li> </ul><li>Uses of PTT</li><ul> <li>(1) Follow heparin therapy</li><ul> <li>(a) Heparin enhances ATIII activity.</li><li>(b) PTT is <i>not</i> required to follow low-molecular-weight heparin therapy.</li> </ul><li>(2) Detect factor deficiencies in the intrinsic system</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC014010"></a> <br><a name="P014010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Fibrin(ogen) degradation products (FDPs)
<blockquote style="color: blue; ">FDPs: increased with lysis of fibrinogen and fibrin in fibrin thrombi</blockquote></li><ul> <li>Detects fragments associated with plasmin degradation of fibrinogen or insoluble fibrin in fibrin clots</li> </ul><li><span style="font-variant:small-caps;">d</span>-Dimer assay
<blockquote style="color: blue; "><span style="font-variant:small-caps;">d</span>-Dimer assay: specific for lysis of fibrin thrombi (clots); detects cross-links</blockquote></li><ol type="a"> <li>Detects cross-linked insoluble fibrin monomers in a fibrin clot</li><li>Does <i>not</i> detect fibrinogen degradation products (not cross-linked)</li><li>Most specific test for evidence of degradation of a fibrin clot (thrombus); examples:</li><ul> <li>(1) Thrombolytic therapy for coronary artery thrombosis</li><ul> <li>Thrombus is composed of platelets held together by fibrin (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>).</li> </ul><li>(2) Screening test for pulmonary thromboembolism</li><ul> <li>Thrombus is composed of RBCs, platelets, WBCs held together by fibrin (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>).</li> </ul><li>(3) Screening test for disseminated intravascular coagulation (DIC)</li><ul> <li>Thrombus is composed of RBCs, platelets, and WBCs held together by fibrin (see Section III).</li> </ul> </ul> </ol> </ol>
</div></html>
![[14.I.A.Factors preventing thrombus formation in small blood vessels]]
<<tiddler [[14.I.A.Factors preventing thrombus formation in small blood vessels]]>>
![[14.I.B.Factors enhancing thrombus formation in small vessel injury]]
<<tiddler [[14.I.B.Factors enhancing thrombus formation in small vessel injury]]>>
![[14.I.C.Platelet structure and function]]
<<tiddler [[14.I.C.Platelet structure and function]]>>
![[14.I.D.Coagulation system (Fig. 14-1)]]
<<tiddler [[14.I.D.Coagulation system (Fig. 14-1)]]>>
![[14.I.E.Fibrinolytic system]]
<<tiddler [[14.I.E.Fibrinolytic system]]>>
![[14.I.F.Small vessel hemostasis response to injury (Fig. 14-2)]]
<<tiddler [[14.I.F.Small vessel hemostasis response to injury (Fig. 14-2)]]>>
![[14.I.G.Platelet tests]]
<<tiddler [[14.I.G.Platelet tests]]>>
![[14.I.H.Coagulation tests (Fig. 14-3)]]
<<tiddler [[14.I.H.Coagulation tests (Fig. 14-3)]]>>
![[14.I.I.Fibrinolytic system tests]]
<<tiddler [[14.I.I.Fibrinolytic system tests]]>>
<html><a name="HC014012"></a> <br><a name="P014014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Quantitative platelet disorders</li><ol type="a"> <li>Thrombocytopenia</li><li>Thrombocytosis</li> </ol><li>Qualitative (functional) platelet disorders</li> </ol>
</div></html>
<html><a name="HC014013"></a> <br><a name="P014015"></a><div class="PA" style="color: black; "><ol type="1"> <li>Thrombocytopenia (<span>[[Table 14-2|Table 14-2. DISORDERS PRODUCING THROMBOCYTOPENIA]]</span>)</li><ul> <li>Decreased number of platelets
<blockquote style="color: blue; ">TTP/HUS: platelet consumption + hemolytic anemia with schistocytes</blockquote></li><ol type="a"> <li>Decreased production</li><ul> <li>Examples-aplastic anemia, leukemia</li> </ul><li>Increased destruction</li><ul> <li>(1) Immune</li><ul> <li>Examples-idiopathic thrombocytopenic purpura, drugs</li> </ul><li>(2) Nonimmune</li><ul> <li>Examples-thrombotic thrombocytopenic purpura, DIC</li> </ul> </ul><li>Sequestration in the spleen</li><ul> <li>Hypersplenism in portal hypertension</li> </ul> </ol> </ul><li>Thrombocytosis</li><ul> <li>Increased platelet count</li><ol type="a"> <li>Primary thrombocytosis</li><ul> <li>Examples-essential thrombocythemia, polycythemia vera (refer to <span macro="tag [[12 White Blood Cell Disorders]] [[Chapter 12]]"></span>)
<blockquote style="color: blue; ">Thrombocytosis: chronic iron deficiency, malignancy, splenectomy</blockquote></li> </ul><li>Secondary (reactive) thrombocytosis</li><ul> <li>Examples-chronic iron deficiency, infections, splenectomy, malignancy</li> </ul> </ol> </ul><li>Qualitative platelet disorders</li><ul> <li>Acquired (e.g., aspirin) or hereditary (e.g., Glanzmann's disease)
<blockquote style="color: blue; ">Aspirin: most common cause of a qualitative platelet defect</blockquote></li> </ul> </ol>
</div></html>
<html><a name="HC014014"></a> <br><a name="PB014004"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Ecchymoses (purpura)</b> can be caused by a variety of disorders unrelated to thrombocytopenia. Palpable purpura (purpura that can be felt) is a sign of a small vessel vasculitis (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>). Because vasculitis is a type of acute inflammation, the lesions are palpable due to increased vessel permeability and <i>not</i> a platelet disorder. Ecchymoses are also present in scurvy (vitamin C deficiency), and are due to vessel weakness related to lack of cross-bridging between tropocollagen molecules (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>). Senile purpura is a normal finding in elderly patients and is due to vessel instability normally associated with aging (<span>[[Fig. 14-5|Figure 14-5]]</span>). Ecchymoses develop in areas of trauma (e.g., back of the hands, shins).</div><a name="P014016"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epistaxis (nosebleeds) is the most common symptom.</li><li>Petechiae and multiple small ecchymoses (purpura); only with thrombocytopenia
<blockquote style="color: blue; ">Petechiae: only with thrombocytopenia</blockquote></li><ol type="a"> <li>Petechiae are pinpoint areas of hemorrhage in subcutaneous tissue (<span>[[Fig. 14-4|Figure 14-4]]</span>).</li><ul> <li>RBCs leak through postcapillary venular gaps in the endothelium.</li> </ul><li>Ecchymoses are the size of a quarter.</li> </ol><li>Bleeding from superficial scratches
<blockquote style="color: blue; ">Senile purpura: vessel instability</blockquote>
<blockquote style="color: blue; ">Platelet dysfunction (e.g., aspirin): bleeding from superficial scratches, easy bruising</blockquote></li><ul> <li>No temporary platelet plug is present to stop bleeding from injury to small vessels.</li> </ul><li>Other findings</li><ol type="a"> <li>Menorrhagia, hematuria</li><li>Bleeding from tooth extraction sites
<blockquote style="color: blue; ">Thrombocytopenia: petechia and above findings</blockquote></li><li>Easy bruiseability</li><li>Gastrointestinal and intracranial bleeding</li> </ol> </ol>
</div></html>
![[14.II.A.Classification of platelet disorders]]
<<tiddler [[14.II.A.Classification of platelet disorders]]>>
![[14.II.B.Pathogenesis]]
<<tiddler [[14.II.B.Pathogenesis]]>>
![[14.II.C.Clinical findings associated with platelet dysfunction]]
<<tiddler [[14.II.C.Clinical findings associated with platelet dysfunction]]>>
<html><a name="HC014016"></a> <br><a name="P014017"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acquired</li><ul> <li>Single or multiple coagulation factor deficiencies</li> </ul><li>Hereditary</li><ul> <li>Usually a single coagulation factor deficiency</li> </ul> </ol>
</div></html>
<html><a name="HC014017"></a> <br><a name="P014018"></a><div class="PA" style="color: black; "><ol type="1"> <li>Decreased production</li><ul> <li>Examples-hemophilia A, cirrhosis</li> </ul><li>Pathologic inhibition</li><ul> <li>Example-acquired circulating antibodies (inhibitors) against coagulation factors</li> </ul><li>Excessive consumption</li><ul> <li>Example-disseminated intravascular coagulation
<blockquote style="color: blue; ">Coagulation disorders: ↓ production, inhibition, consumption</blockquote></li> </ul> </ol>
</div></html>
<html><a name="HC014018"></a> <br><a name="P014019"></a><div class="PA" style="color: black; "><ol type="1"> <li>Late rebleeding after surgery or wisdom tooth extraction</li><ol type="a"> <li>Temporary platelet plug is the only mechanical block preventing bleeding.</li><li>Lack of thrombin prevents formation of a stable platelet plug held together by fibrin.</li> </ol><li>Findings in severe factor deficiencies</li><ol type="a"> <li>Hemarthroses</li><li>Retroperitoneal and deep muscular bleeding
<blockquote style="color: blue; ">Coagulation disorders: late rebleeding; hemarthroses (severe deficiency)</blockquote></li> </ol><li>Findings similar to platelet disorders</li><ol type="a"> <li>Ecchymoses, epistaxis</li><li>Menorrhagia, hematuria</li><li>Bleeding from tooth extraction sites</li><li>Easy bruiseability</li><li>Gastrointestinal and intracranial bleeding</li> </ol> </ol>
</div></html>
![[14.III.A.Classification of coagulation disorders]]
<<tiddler [[14.III.A.Classification of coagulation disorders]]>>
![[14.III.B.Pathogenesis]]
<<tiddler [[14.III.B.Pathogenesis]]>>
![[14.III.C.Clinical findings in coagulation disorders]]
<<tiddler [[14.III.C.Clinical findings in coagulation disorders]]>>
![[14.III.D.Hemophilia A]]
<<tiddler [[14.III.D.Hemophilia A]]>>
![[14.III.E.Classic von Willebrand disease]]
<<tiddler [[14.III.E.Classic von Willebrand disease]]>>
![[14.III.F.Circulating anticoagulants (inhibitors)]]
<<tiddler [[14.III.F.Circulating anticoagulants (inhibitors)]]>>
![[14.III.G.Vitamin K deficiency]]
<<tiddler [[14.III.G.Vitamin K deficiency]]>>
![[14.III.H.Hemostasis disorders in liver disease]]
<<tiddler [[14.III.H.Hemostasis disorders in liver disease]]>>
![[14.III.I.Disseminated intravascular coagulation]]
<<tiddler [[14.III.I.Disseminated intravascular coagulation]]>>
<html><a name="HC014019"></a> <br><a name="PB014005"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Hemophilia B</b> (Christmas disease) is an X-linked recessive disorder involving a deficiency of factor IX. It is clinically indistinguishable from hemophilia A.</div><a name="P014020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>X-linked recessive
<blockquote style="color: blue; ">Hemophilia A: X-linked recessive</blockquote></li><ul> <li>(1) Females are asymptomatic carriers.</li><li>(2) Females transmit the abnormal X chromosome to 50% of their sons.</li> </ul><li>Absent family history of hemophilia</li><ul> <li>Most likely due to a new mutation (30% of cases)</li> </ul><li>Female carriers with symptomatic disease</li><ul> <li>(1) Due to inactivation of more maternal than paternal X chromosomes</li><li>(2) Females become "homozygous" for the abnormal X chromosome.</li> </ul> </ol><li>Pathogenesis</li><ul> <li>Decreased synthesis of factor VIII:c, a coagulation factor in the intrinsic system</li> </ul><li>Clinical findings in hemophilia A</li><ol type="a"> <li>Signs and symptoms correlate with the level of factor VIII:c activity
<blockquote style="color: blue; ">Hemophilia A: % VIII:c never changes; correlates with severity of disease</blockquote></li><ul> <li>(1) Mild disease is 5% to 25% of normal.</li><li>(2) Moderate disease is 1% to 4% of normal.</li><li>(3) Severe disease is <1% of normal.</li> </ul><li>Bleeding problems may occur in newborns (10-15% of cases).</li><ul> <li>Excessive bleeding may occur after circumcision or umbilical cord separation.</li> </ul><li>Laboratory findings in hemophilia A
<blockquote style="color: blue; ">Hemophilia B: X-linked recessive; factor IX deficiency</blockquote></li><ul> <li>(1) Increased PTT and a normal PT</li><li>(2) Decreased factor VIII:c activity
<blockquote style="color: blue; ">Hemophilia A: ↓ VIII:c; ↑ PTT</blockquote></li><li>(3) Detection of female carriers</li><ul> <li>DNA techniques are most sensitive.</li> </ul> </ul> </ol><li>Treatment of hemophilia A</li><ol type="a"> <li>Mild cases respond to desmopressin acetate</li><ul> <li>Increases release of VIII:c from storage sites</li> </ul><li>Severe cases require infusion of recombinant factor VIII</li><ul> <li><i>No</i> risk for HIV</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC014020"></a> <br><a name="P014021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal dominant disorder
<blockquote style="color: blue; ">vWD: AD inheritance</blockquote></li><li>Most common hereditary coagulation disorder</li><li>Several subtypes</li><ul> <li>Type I (80%; only one discussed), type IIA, type IIB, type III</li> </ul><ul> <li>(1) Some differ in inheritance pattern.</li><li>(2) Some differ in ristocetin cofactor assay results.</li><li>(3) Some have abnormal multimer patterns on agar electrophoresis.</li><li>(4) Some differ in ristocetin-induced platelet aggregation.</li><li>(5) Some differ in VIII:c activity.
<blockquote style="color: blue; ">vWD associations: MVP, Marfan syndrome, angiodysplasia</blockquote></li> </ul><li>Associations</li><ul> <li>(1) Mitral valve prolapse (MVP)</li><li>(2) Marfan syndrome</li><li>(3) Angiodysplasia
<blockquote style="color: blue; ">vWD: most common hereditary coagulation disorder</blockquote></li> </ul> </ol><li>Pathogenesis</li><ul> <li>Decreased vWF and factor VIII:c activity</li> </ul><li>Clinical findings in vWD</li><ol type="a"> <li>Menorrhagia
<blockquote style="color: blue; ">vWD: combined platelet and coagulation factor disorder</blockquote></li><li>Epistaxis</li><li>Easy bruiseability</li> </ol><li>Laboratory findings in vWD</li><ol type="a"> <li>Increased PTT and a normal PT</li><li>Increased bleeding time</li><ul> <li>Due to a platelet adhesion defect</li> </ul><li>Abnormal ristocetin cofactor assay
<blockquote style="color: blue; ">vWD: ↑ PTT, bleeding time; ↓ VIII:c, vWF</blockquote></li><li>Decreased vWF antigen</li><li>Decreased VIII:c activity</li> </ol><li>Treatment of vWD</li><ol type="a"> <li>Desmopressin acetate or estrogen in oral contraceptive pills (OCPs) (women)</li><ul> <li>Increases release of vWF and VIII:c from storage sites</li> </ul><li>Severe cases require infusion of recombinant factor VIII
<blockquote style="color: blue; ">Rx vWD: desmopressin acetate, OCP</blockquote></li> </ol> </ol>
</div></html>
<html><a name="HC014021"></a> <br><a name="P014022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Coagulation factor is destroyed by antibodies.</li><li>Most common type is antibodies against factor VIII:c (e.g., postpartum).</li> </ol><li>Clinical findings</li><ul> <li>Similar to those with coagulation factor deficiencies due to decreased production</li> </ul><li>Laboratory findings</li><ol type="a"> <li>Prolonged PT or PTT, depending on the factor deficiency</li><ul> <li>Does <i>not</i> differentiate immune destruction versus decreased production</li> </ul><li>Mixing studies</li><ul> <li>(1) Normal plasma is mixed with patient plasma in a test tube.</li><li>(2) <i>No</i> correction of PT or PTT indicates immune destruction.
<blockquote style="color: blue; ">Circulating anticoagulant: PT and PTT <i>not</i> corrected with mixing study</blockquote></li><li>(3) Correction of PT and PTT indicates decreased production.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC014022"></a> <br><a name="PB014006"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Warfarin</b> is an anticoagulant that inhibits epoxide reductase, which prevents any further γ-carboxylation of the vitamin K-dependent coagulation factors. However, full anticoagulation does <i>not</i> immediately occur, because previously γ-carboxylated factors are still present. Prothrombin has the longest half-life; therefore, full anticoagulation requires at least 3-4 days before all functional prothrombin has disappeared. This explains why patients are initially placed on both heparin and warfarin, because heparin immediately anticoagulates the patient by enhancing ATIII activity.
<blockquote style="color: blue; ">Warfarin: inhibits epoxide reductase; vitamin K is nonfunctional</blockquote></div><a name="P014023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Function of vitamin K</li><ul> <li>γ-Carboxylates vitamin K-dependent factors II, VII, IX, X and proteins C and S
<blockquote style="color: blue; ">Vitamin K-dependent factors: II, VII, IX, X, protein C and S; γ-carboxylation activates them</blockquote></li> </ul><li>Causes of vitamin K deficiency</li><ol type="a"> <li>Decreased synthesis of vitamin K by colonic bacteria</li><ul> <li>(1) Newborns lack bacterial colonization of the bowel.</li><ul> <li>(a) Vitamin K levels normally decrease between days 2 and 5.</li><li>(b) Danger of severe bleeding (e.g., intracerebral hemorrhage)</li><li>(c) Newborns require an intramuscular injection of vitamin K at birth.
<blockquote style="color: blue; ">Newborns: lack bacterial colonization in bowel; no synthesis vitamin K</blockquote></li><ul> <li>Breast milk contains very little vitamin K.</li> </ul> </ul><li>(2) Prolonged treatment with antibiotics</li><ul> <li>(a) Antibiotics sterilize the bowel causing decreased production of vitamin K.</li><li>(b) Most common cause of vitamin K deficiency in a hospitalized patient
<blockquote style="color: blue; ">Vitamin K deficiency in hospitalized patient: due to antibiotic therapy</blockquote></li> </ul> </ul><li>Decreased small bowel reabsorption of vitamin K</li><ul> <li>(1) Malabsorption of fat causes malabsorption of fat-soluble vitamins.</li><li>(2) Example-celiac disease</li> </ul><li>Decreased activation of vitamin K by epoxide reductase in the liver</li><ul> <li>(1) Warfarin inhibits epoxide reductase.</li><ul> <li>(a) Vitamin K-dependent factors are nonfunctional.</li><li>(b) Rat poison contains warfarin.
<blockquote style="color: blue; ">Rat poison: contains warfarin</blockquote></li><li>(c) Children may have exposure to warfarin from elders living in the household.</li> </ul><li>(2) Cirrhosis</li><ul> <li>(a) Decreased activation of vitamin K and synthesis of vitamin K-dependent coagulation factors</li><li>(b) Prolonged PT is <i>not</i> corrected with intramuscular injection of vitamin K.
<blockquote style="color: blue; ">Cirrhosis: ↓ synthesis of vitamin K-dependent factors, ↓ activation of vitamin K</blockquote></li> </ul> </ul> </ol><li>Clinical findings of vitamin K deficiency</li><ol type="a"> <li>Gastrointestinal bleeding</li><li>Bleeding into subcutaneous tissue</li><li>Bleeding at the time of circumcision</li><li>Intracranial hemorrhage</li> </ol><li>Treatment of vitamin K deficiency</li><ol type="a"> <li>If bleeding is <i>not</i> severe, treatment is an intramuscular injection of vitamin K.</li><ul> <li>Corrects bleeding in a few hours</li> </ul><li>If bleeding is severe, treatment is with fresh frozen plasma.</li><ul> <li>(1) Immediate correction</li><li>(2) Vitamin K-dependent factors are γ-carboxylated.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC014023"></a> <br><a name="P014024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis
<blockquote style="color: blue; ">Cirrhosis: multiple hemostasis abnormalities</blockquote></li><ol type="a"> <li>Decreased synthesis of coagulation factors</li><ul> <li>(1) Multiple coagulation factor deficiencies</li><li>(2) Decreased γ-carboxylation of vitamin K-dependent factors</li> </ul><li>Decreased synthesis of anticoagulants</li><ul> <li>Examples-ATIII, proteins C and S</li> </ul><li>Decreased synthesis of fibrinolytic agents (e.g., plasminogen)</li><li>Decreased clearance of FDPs and <span style="font-variant:small-caps;">d</span>-dimers</li><ul> <li>Interfere with platelet aggregation and polymerization of fibrin</li> </ul><li>Decreased clearance of tPA and decreased synthesis of α<sub>2</sub>-antiplasmin</li><ul> <li>May produce primary fibrinolysis (see section IV)</li> </ul> </ol><li>Laboratory findings in liver disease</li><ol type="a"> <li>Increased PT and PTT</li><li>Increased FDPs and <span style="font-variant:small-caps;">d</span>-dimers</li><li>Increased bleeding time</li> </ol> </ol>
</div></html>
<html><a name="HC014024"></a> <br><a name="P014025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes of DIC</li><ol type="a"> <li>Sepsis (>50% of cases)
<blockquote style="color: blue; ">Sepsis: most common cause of DIC</blockquote></li><ul> <li>(1) Common pathogens are <i>E. coli</i> (most common) and <i>Neisseria meningitidis</i>.</li><li>(2) Others include Rocky Mountain spotted fever and malaria.</li> </ul><li>Disseminated malignancy</li><ul> <li>(1) Acute promyelocytic leukemia</li><li>(2) Pancreatic cancer with release of procoagulants in mucin</li> </ul><li>Other causes</li><ul> <li>(1) Crush injuries</li><li>(2) Rattlesnake envenomation</li><li>(3) Amniotic fluid embolism</li><li>(4) Disseminated malignancy</li><li>(5) Abruptio placentae</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Activation of the coagulation cascade</li><ul> <li>Due to release of tissue thromboplastin or endothelial cell injury</li> </ul><li>Fibrin thrombi develop in the microcirculation.</li><ul> <li>(1) Thrombi obstruct blood flow.</li><li>(2) Thrombi consume coagulation factors (I, II, V, VIII) and trap platelets.
<blockquote style="color: blue; ">DIC: consumption of coagulation factors</blockquote></li> </ul><li>Activation of the fibrinolytic system</li><ul> <li>Secondary fibrinolysis due to activation of plasminogen by factor XII</li> </ul> </ol><li>Clinical findings in DIC
<blockquote style="color: blue; ">DIC: thrombohemorrhagic disorder</blockquote></li><ol type="a"> <li>Thrombohemorrhagic disorder</li><ul> <li>(1) Ischemia from occlusive fibrin thrombi</li><li>(2) Bleeding from anticoagulation</li><ul> <li>Factors I, II, V, and VIII are consumed in production of the fibrin thrombi.</li> </ul><li>(3) Bleeding from interference with platelet aggregation by fibrinogen degradation products</li> </ul><li>Hypovolemic shock due to blood loss</li><li>Diffuse oozing of blood from all breaks in the skin and mucous membranes</li><li>Petechiae and ecchymoses from thrombocytopenia</li> </ol><li>Laboratory findings in DIC
<blockquote style="color: blue; ">Lab findings: ↑ PT, PTT, <span style="font-variant:small-caps;">d</span>-dimers, BT; ↓ platelets</blockquote></li><ol type="a"> <li>Coagulation abnormalities</li><ul> <li>(1) Increased PT and PTT</li><li>(2) Decreased fibrinogen</li> </ul><li>Platelet abnormalities</li><ul> <li>(1) Thrombocytopenia</li><li>(2) Increased bleeding time</li> </ul><li>Fibrinolysis abnormalities</li><ul> <li>Presence of FDPs and <span style="font-variant:small-caps;">d</span>-dimers
<blockquote style="color: blue; "><span style="font-variant:small-caps;">d</span>-Dimers: most sensitive screen for DIC</blockquote></li> </ul><li>Normocytic anemia</li><ul> <li>(1) Bleeding from different sites</li><li>(2) Microangiopathic hemolytic anemia with schistocytes</li><ul> <li>RBCs are damaged by fibrin thrombi.</li> </ul> </ul> </ol><li>Treatment</li><ol type="a"> <li>Treating the underlying disease is most important!
<blockquote style="color: blue; ">DIC Rx: treat underlying disease most important; component replacement</blockquote></li><li>Transfuse blood components</li><ul> <li>(1) Fresh frozen plasma for multiple coagulation factor deficiencies</li><li>(2) Packed RBCs for anemia</li><li>(3) Platelet concentrates for thrombocytopenia</li><li>(4) Cryoprecipitate for fibrinogen deficiency (if warranted)</li> </ul><li>Low-dose heparin in selected cases (controversial)</li> </ol> </ol>
</div></html>
<html><a name="HC014026"></a> <br><a name="P014028"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes</li><ol type="a"> <li>Open heart surgery</li><ul> <li>Cardiopulmonary bypass causes a decrease in α<sub>2</sub>-antiplasmin and increase in tPA.</li> </ul><li>Radical prostatectomy</li><ul> <li>Causes increased release of urokinase</li> </ul><li>Diffuse liver disease</li><ul> <li>Causes a decrease in the synthesis of α<sub>2</sub>-antiplasmin</li> </ul> </ol><li>Pathogenesis
<blockquote style="color: blue; ">Primary fibrinolysis: open heart surgery, prostatectomy, diffuse liver disease</blockquote></li><ol type="a"> <li>FDPs interfere with platelet aggregation.</li><li>Plasmin degrades coagulation factors causing multiple factor deficiencies.</li> </ol><li>Clinical findings</li><ul> <li>Severe bleeding</li> </ul><li>Laboratory findings
<blockquote style="color: blue; ">Primary fibrinolysis: - test for FDPs, <span style="font-variant:small-caps;">d</span>-dimers; normal platelet count; ↑ PT and PTT</blockquote></li><ol type="a"> <li>Increased PT and PTT</li><ul> <li>Due to multiple factor deficiencies</li> </ul><li>Increased bleeding time</li><ul> <li>Due to interference with platelet aggregation</li> </ul><li>Positive test for FDPs</li><li>Negative <span style="font-variant:small-caps;">d</span>-dimer assay</li><ul> <li><i>No</i> fibrin thrombi are present.</li> </ul><li>Normal platelet count</li> </ol><li>Treatment</li><ul> <li>Aminocaproic acid</li> </ul> </ol>
</div></html>
<html><a name="HC014027"></a> <br><a name="P014029"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Secondary fibrinolysis: <span style="font-variant:small-caps;">d</span>-dimer and FDPs; ↓ platelet count; ↑ PT and PTT</blockquote>
<ol type="1"> <li>Compensatory reaction in the presence of DIC</li><li>Increase in both FDPs and <span style="font-variant:small-caps;">d</span>-dimers</li> </ol>
</div></html>
![[14.IV.A.Primary fibrinolysis]]
<<tiddler [[14.IV.A.Primary fibrinolysis]]>>
![[14.IV.B.Secondary fibrinolysis]]
<<tiddler [[14.IV.B.Secondary fibrinolysis]]>>
<html><a name="HC014028"></a><span>[[Table 14-3|Table 14-3. LABORATORY FINDINGS IN COMMON HEMOSTASIS DISORDERS]]</span> <br> <br> </html>
![[14.V.A.Summary of Laboratory Test Results in Hemostasis Disorders (Table 14-3)]]
<<tiddler [[14.V.A.Summary of Laboratory Test Results in Hemostasis Disorders (Table 14-3)]]>>
<html><a name="HC014030"></a> <br><a name="P014030"></a><div class="PA" style="color: black; "><ol type="1"> <li>Antiphospholipid syndrome (APLS)</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Highest association with SLE</li><li>(2) Other diseases: rheumatoid arthritis, Sjögren's syndrome, HIV infection</li> </ul><li>Pathogenesis
<blockquote style="color: blue; ">APAs: anticardiolipin antibody, lupus anticoagulant</blockquote></li><ul> <li>(1) Presence of antiphospholipid antibodies (APAs)</li><ul> <li>Directed against phospholipids bound to plasma proteins</li> </ul><li>(2) APAs include:
<blockquote style="color: blue; ">APLS: thrombosis syndrome</blockquote></li><ul> <li>(a) Anticardiolipin antibody and lupus anticoagulant</li><ul> <li>Anticardiolipin antibody reacts with the cardiolipin reagent in the rapid plasma reagin test for syphilis.</li> </ul><li>(b) Lupus anticoagulant</li><li>(c) Anti-β<sub>2</sub> glycoprotein-1 antibodies
<blockquote style="color: blue; ">Anticardiolipin antibody: false positive syphilis serologic test</blockquote></li> </ul><li>(3) Produce arterial and venous thrombosis syndromes</li><ul> <li>Venous thrombi more common than arterial</li> </ul> </ul><li>Clinical findings in APLS</li><ul> <li>(1) Repeated spontaneous abortions
<blockquote style="color: blue; ">APLS: spontaneous abortions, strokes, deep vein thrombosis, hepatic vein thrombosis</blockquote></li><ul> <li>Due to thrombosis of placental bed vessels</li> </ul><li>(2) Strokes</li><li>(3) Deep vein thrombosis</li><li>(4) Hepatic vein thrombosis</li> </ul><li>Laboratory findings</li><ul> <li>(1) False positive syphilis serologic test</li><ul> <li>If anticardiolipin antibodies are present</li> </ul><li>(2) Lupus anticoagulant</li><ul> <li>Prolonged PTT that does <i>not</i> correct with mixing studies</li> </ul><li>(3) Anticardiolipin antibodies</li><ul> <li>Most sensitive and specific test (>80%)</li> </ul><li>(4) Anti-β<sub>2</sub> glycoprotein-1 antibodies</li> </ul><li>Treatment</li><ul> <li>(1) Depends on the clinical presentation</li><li>(2) In general, initiate anticoagulation with heparin and keep on lifelong warfarin treatment</li> </ul> </ol><li>Other acquired causes of thrombosis
<blockquote style="color: blue; ">Other thrombosis syndromes: post-op state, malignancy, OCPs, ↓ folate/B<sub>12</sub>, hypersensitivity</blockquote></li><ol type="a"> <li>Postoperative state with stasis of blood flow</li><li>Malignancy</li><ul> <li>(1) Increase in coagulation factors</li><li>(2) Thrombocytosis</li><li>(3) Release of procoagulants from tumors, particularly pancreatic cancers</li> </ul><li>Folate or vitamin B<sub>12</sub> deficiency</li><ul> <li>Due to increased plasma homocysteine levels</li> </ul><li>OCPs</li><ul> <li>Estrogen increases the synthesis of coagulation factors and decreases ATIII</li> </ul><li>Hyperviscosity</li><ul> <li>(1) Polycythemia syndromes</li><li>(2) Waldenström's macroglobulinemia</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC014031"></a> <br><a name="P014031"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal dominant syndromes</li><li>Deep venous thrombosis and pulmonary emboli occur at an early age.</li><li>Venous thromboses often occur in unusual places.</li><ul> <li>Examples-hepatic vein, dural sinus</li> </ul> </ol><li>Factor V Leiden
<blockquote style="color: blue; ">Factor V Leiden: most common hereditary thrombosis syndrome</blockquote></li><ol type="a"> <li>Most common hereditary thrombosis syndrome</li><li>Mutant form of factor V <i>cannot</i> be degraded by protein C and protein S.</li> </ol><li>Antithrombin III (ATIII) deficiency</li><ol type="a"> <li>Functions of ATIII</li><ul> <li>(1) Activity is enhanced by heparin.</li><li>(2) Neutralizes activated serine proteases</li><ul> <li>Example-factors XII, XI, IX, X, thrombin</li> </ul> </ul><li><i>No</i> prolongation of PTT after injecting a standard dose of heparin
<blockquote style="color: blue; ">ATIII deficiency: normal PTT after standard dose heparin</blockquote></li><li>Treatment</li><ul> <li>(1) Infuse a greater dose of heparin than normal</li><ul> <li>PTT eventually increases due to enhancement of whatever ATIII is present.</li> </ul><li>(2) Send the patient home on warfarin.</li> </ul> </ol><li>Proteins C and S deficiency</li><ol type="a"> <li>Pathogenesis</li><ul> <li>Cannot inactivate factors V and VIII</li> </ul><li>Treatment</li><ul> <li>(1) Begin with heparin and a very low dose of warfarin to reduce the risk for developing hemorrhagic skin necrosis.</li><li>(2) Send the patient home on warfarin.</li> </ul> </ol> </ol>
</div><a name="PB014007"></a><div class="BB" style="color: rgb(47, 79, 79); ">There is a potential for heterozygote carriers of protein C deficiency to develop hemorrhagic skin necrosis when placed on warfarin. Heterozygote carriers have ∼50% protein C activity. Protein C has a short half-life (∼6 hours). When these patients are placed on warfarin, protein C activity falls to zero activity in 6 hours, causing a hypercoagulable state due to increased activity of factors V and VIII. This causes cutaneous vessel thrombosis and concomitant skin necrosis. This complication is not likely to occur in normal people.
<blockquote style="color: blue; ">Hemorrhagic skin necrosis: associated with warfarin therapy in protein C deficiency</blockquote></div></html>
![[14.VI.A.Acquired thrombosis syndromes]]
<<tiddler [[14.VI.A.Acquired thrombosis syndromes]]>>
![[14.VI.B.Hereditary thrombosis syndromes]]
<<tiddler [[14.VI.B.Hereditary thrombosis syndromes]]>>
<html><a name="HC015002"></a> <br><a name="P015001"></a><div class="PA" style="color: black; "><ul> <li>They are glycoproteins attached to the RBC surface.</li> </ul>
</div></html>
![[15.I.A.Definition of ABO blood group antigens]]
<<tiddler [[15.I.A.Definition of ABO blood group antigens]]>>
![[15.I.B.Blood group O characteristics]]
<<tiddler [[15.I.B.Blood group O characteristics]]>>
![[15.I.C.Blood group A characteristics]]
<<tiddler [[15.I.C.Blood group A characteristics]]>>
![[15.I.D.Blood group B characteristics]]
<<tiddler [[15.I.D.Blood group B characteristics]]>>
![[15.I.E.Blood group AB characteristics]]
<<tiddler [[15.I.E.Blood group AB characteristics]]>>
![[15.I.F.Newborns]]
<<tiddler [[15.I.F.Newborns]]>>
![[15.I.G.Elderly people]]
<<tiddler [[15.I.G.Elderly people]]>>
![[15.I.H.Paternity issues in newborns]]
<<tiddler [[15.I.H.Paternity issues in newborns]]>>
![[15.I.I.Determining the ABO group (Fig. 15-2)]]
<<tiddler [[15.I.I.Determining the ABO group (Fig. 15-2)]]>>
<html><a name="HC015003"></a> <br><a name="PB015001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Blood group antibodies</b> are natural antibodies that are synthesized in Peyer's patches. A and B antigens that are normally present in food are trapped by specialized epithelial cells called M cells that overlie Peyer's patches. M cells have close proximity to B lymphocytes lying within the epithelium. M cells transport the A and B antigens to these lymphocytes, resulting in the development of natural antibodies against the antigens. Natural antibodies develop against antigens that are <i>not</i> present on the RBC, which explains why blood group O patients have antibodies against both A and B antigens.
<blockquote style="color: blue; ">M cells: transport A and B antigens in Peyer's patches to B lymphocytes</blockquote></div><a name="P015002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common blood group</li><ul> <li><i>No</i> blood group antigens are present on the RBC membrane.
<blockquote style="color: blue; ">Blood group O: most common blood group</blockquote></li> </ul><li>Natural antibodies (isohemagglutinins) in serum</li><ol type="a"> <li>Anti-A-IgM, anti-B-IgM</li><li>Most people have anti-A and B-IgG antibodies.
<blockquote style="color: blue; ">Group O: anti-A-IgM, anti-B-IgM, anti-A and B-IgG</blockquote></li> </ol><li>Increased incidence of duodenal ulcers</li> </ol>
</div></html>
<html><a name="HC015004"></a> <br><a name="P015003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Anti-B-IgM antibodies
<blockquote style="color: blue; ">Group A: anti-B-IgM</blockquote></li><li>Increased incidence of gastric carcinoma</li> </ol>
</div></html>
<html><a name="HC015005"></a> <br><a name="P015004"></a><div class="PA" style="color: black; "><ul> <li>Anti-A-IgM antibodies
<blockquote style="color: blue; ">Group B: anti-A-IgM</blockquote></li> </ul>
</div></html>
<html><a name="HC015006"></a> <br><a name="P015005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Least common blood group</li><li><i>No</i> natural antibodies
<blockquote style="color: blue; ">Group AB: no natural antibodies</blockquote></li> </ol>
</div></html>
<html><a name="HC015007"></a> <br><a name="P015006"></a><div class="PA" style="color: black; "><ol type="1"> <li>Do <i>not</i> have natural antibodies at birth
<blockquote style="color: blue; ">Newborns: lack natural antibodies</blockquote></li><li>IgG antibodies are of maternal origin.</li><ul> <li>IgG antibodies cross the placenta.</li> </ul> </ol>
</div></html>
<html><a name="HC015008"></a> <br><a name="PB015002"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Elderly patients</b> may <i>not</i> have a hemolytic transfusion reaction if they are transfused with the wrong blood group because they frequently lose their natural antibodies.</div><a name="P015007"></a><div class="PA" style="color: black; "><ul> <li>Frequently lose their natural antibodies
<blockquote style="color: blue; ">Elderly people: frequently lose natural antibodies</blockquote></li> </ul>
</div></html>
<html><a name="HC015009"></a> <br><a name="P015008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Blood group AB parents <i>cannot</i> have an O child.</li><li>Blood group O parents <i>cannot</i> have an AB, A, or B child.
<blockquote style="color: blue; ">Blood group AB parents: cannot have O child</blockquote></li><li>Blood group A and B parents can have O children if both have AO and BO phenotypes (<span>[[Fig. 15-1|Figure 15-1]]</span>).
<blockquote style="color: blue; ">Blood group O parents: cannot have AB, A, or B child</blockquote></li> </ol>
</div></html>
<html><a name="HC015010"></a><span>[[Fig. 15-2|Figure 15-2]]</span> <br> <br><a name="P015009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Forward type</li><ol type="a"> <li>Identifies the blood group antigen
<blockquote style="color: blue; ">Forward typing: identifies blood group antigen</blockquote></li><ul> <li>Patient RBCs are added to test tubes that contain either anti-A or anti-B test serum.</li> </ul><li>Example-blood group A RBCs</li><ul> <li>Agglutination reaction with anti-A test serum but <i>not</i> with anti-B test serum</li> </ul> </ol><li>Back type
<blockquote style="color: blue; ">Back typing: identifies natural antibodies</blockquote></li><ol type="a"> <li>Identifies the natural antibodies</li><ul> <li>Patient serum is added to test tubes containing either A or B test RBCs.</li> </ul><li>Example-blood group A serum</li><ul> <li>Patient anti-B-IgM antibodies agglutinate B test RBCs but <i>not</i> A test RBCs.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC015012"></a> <br><a name="P015012"></a><div class="PA" style="color: black; "><ol type="1"> <li>It has three adjoining gene loci.
<blockquote style="color: blue; ">Five Rh antigens: D, C, c, E, e</blockquote></li><ol type="a"> <li>Locus coding for D antigen (no d antigen)</li><li>Locus coding for C and c antigen</li><li>Locus coding for E and e antigen</li> </ol><li>Autosomal codominant inheritance</li><ol type="a"> <li>One of the sets of three Rh antigens from each parent is transmitted to each child.</li><ul> <li>(1) Example-child with cDe from the mother and cde from the father (<span>[[Fig. 15-3|Figure 15-3]]</span>)</li><ul> <li>Note that the child lacks E antigen.</li> </ul><li>(2) Absence of D antigen on a chromosome is designated d even though the antigen does <i>not</i> exist.</li> </ul><li>Possible Rh antigen profiles</li><ul> <li>(1) DD, Dd, or dd</li><li>(2) CC, Cc, or cc</li><li>(3) EE, Ee, or ee</li> </ul> </ol><li>An individual who is Rh positive is D antigen positive.
<blockquote style="color: blue; ">Rh positive: D antigen positive</blockquote></li><li>Approximately 85% of the population has D antigen.</li><ul> <li>Individuals lacking D antigen are considered Rh negative.</li> </ul><li>Rh phenotype of an individual</li><ol type="a"> <li>RBCs are reacted with test antisera against each of the Rh antigens.</li><li>Example-Rh phenotype that is positive for C, c, D, and E antigens but negative for e antigen (phenotype is CcDE)</li> </ol> </ol>
</div></html>
<html><a name="HC015013"></a> <br><a name="P015013"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Alloimmunization: antibodies develop against foreign antigens</blockquote>
<ol type="1"> <li>Production of an antibody against a foreign antigen <i>not</i> present on an individual's RBCs</li><ol type="a"> <li>Patient exposure to Rh antigen he is lacking (e.g., D antigen)</li><li>Patient exposure to non-Rh antigen she is lacking (e.g., Kell antigen)</li><li>These antibodies are called atypical antibodies.</li><ul> <li>The individual is considered sensitized if atypical antibodies are present.</li> </ul> </ol><li>Significance of atypical antibodies
<blockquote style="color: blue; ">Atypical antibodies: may produce an HTR</blockquote></li><ol type="a"> <li>May produce a hemolytic transfusion reaction (HTR)</li><ul> <li>(1) Occurs when blood containing the foreign antigen is infused into an individual</li><li>(2) Example-individual with anti-Kell antibodies is exposed to Kell antigen positive RBCs.</li><li>(3) IgG antibodies are more likely to produce an HTR than IgM antibodies.</li><ul> <li>IgG antibodies react best in warm temperatures, but IgM antibodies react best in cold temperatures.</li> </ul> </ul><li>Transfusion requirements in an individual with atypical antibodies</li><ul> <li>(1) Individual must receive blood that is negative for the foreign antigen.
<blockquote style="color: blue; ">Individual with an atypical antibody must receive blood lacking the antigen.</blockquote></li><li>(2) Example-individual with anti-Kell antibodies must receive Kell antigen negative blood.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC015014"></a> <br><a name="P015014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Duffy (Fy) antigens</li><ol type="a"> <li>Fy antigens are the binding site for infestation of RBCs by <i>Plasmodium vivax</i>.</li><li>Majority of blacks lack the Fy antigen.</li><ul> <li>Offers protection against contracting <i>P. vivax</i> malaria
<blockquote style="color: blue; ">Fy antigen negative RBCs: protection against <i>P. vivax</i> malaria</blockquote></li> </ul> </ol><li>I and i antigen systems</li><ol type="a"> <li>IgM antibodies (cold agglutinins) may develop against I or i antigen.</li><li>Increased risk for developing a cold autoimmune hemolytic anemia (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li><ul> <li>(1) Anti-i hemolytic anemia may occur in infectious mononucleosis.</li><li>(2) Anti-I hemolytic anemia may occur in <i>Mycoplasma pneumoniae</i> infections.</li> </ul> </ol> </ol>
</div></html>
![[15.II.A.Rh antigen system]]
<<tiddler [[15.II.A.Rh antigen system]]>>
![[15.II.B.Alloimmunization]]
<<tiddler [[15.II.B.Alloimmunization]]>>
![[15.II.C.Clinically important non-Rh antigens]]
<<tiddler [[15.II.C.Clinically important non-Rh antigens]]>>
<html><a name="HC015016"></a> <br><a name="PB015003"></a><div class="BB" style="color: rgb(47, 79, 79); ">There is a risk for <b>transmitting infection when transfusing blood</b>, because there is an incubation period <i>before</i> specific antibodies are developed against the pathogen. The risk for developing an infection per unit of blood in the post-nucleic acid testing era has markedly reduced the risk for transmission of HBV, HCV, and HIV. The most common infectious agent transmitted by blood transfusion is cytomegalovirus (CMV), which is present in donor lymphocytes. When newborns receive transfusions, the blood must be irradiated to destroy lymphocytes that may be carrying CMV. Because a newborn's cellular immunity is <i>not</i> fully developed, a CMV infection would likely be disseminated.
<blockquote style="color: blue; ">Newborn transfusion: must irradiate blood to destroy lymphocytes</blockquote></div><a name="P015016"></a><div class="PA" style="color: black; "><ol type="1"> <li>Autologous transfusion</li><ol type="a"> <li>Process of collection, storage, and reinfusion of the individual's own blood</li><li>Safest form of transfusion
<blockquote style="color: blue; ">Autologous transfusion: safest transfusion</blockquote></li> </ol><li>Tests performed on donor blood</li><ol type="a"> <li>Group (ABO) and type (Rh)</li><li>Antibody screen (indirect Coombs' test)</li><ul> <li>Detects atypical antibodies (e.g., anti-D, anti-Kell)</li> </ul><li>Screening tests for infectious disease</li><ul> <li>Examples-syphilis, hepatitis B and C, human immunodeficiency virus (HIV-1 and 2), human T-lymphotrophic virus (HTLV-1)
<blockquote style="color: blue; ">CMV: most common pathogen transmitted by transfusion</blockquote></li> </ul> </ol> </ol>
</div></html>
<html><a name="HC015017"></a> <br><a name="PB015004"></a><div class="BB" style="color: rgb(47, 79, 79); ">Patients with a negative antibody screen should have a compatible crossmatch. However, a compatible crossmatch does <i>not</i> guarantee that the recipient will not develop atypical antibodies, a transfusion reaction, or an infection.
<blockquote style="color: blue; ">A negative antibody screen ensures that a major crossmatch will be compatible.</blockquote></div><a name="PB015005"></a><div class="BB" style="color: rgb(47, 79, 79); ">Before blood is transfused into newborns or patients with T-cell deficiencies, it must be irradiated to kill donor lymphocytes. This prevents the patient from developing a graft-versus-host reaction (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>) or a disseminated CMV infection.</div><a name="P015017"></a><div class="PA" style="color: black; "><ol type="1"> <li>Components of a standard crossmatch</li><ol type="a"> <li>ABO group and Rh type</li><li>Antibody screen for atypical antibodies</li><li>Direct Coombs' test to identify atypical IgG antibodies on patient RBCs</li><li>Major crossmatch</li> </ol><li>Major crossmatch</li><ol type="a"> <li>Purpose of a major crossmatch</li><ul> <li>Detect atypical antibodies that are directed against foreign antigens on donor RBCs
<blockquote style="color: blue; ">Major crossmatch: patient serum + donor RBCs</blockquote></li> </ul><li>Patient serum is mixed with a sample of RBCs from a donor unit.</li><ul> <li>(1) Each unit of donor blood must have a separate crossmatch.</li><li>(2) Lack of RBC agglutination or hemolysis indicates a compatible crossmatch.</li> </ul> </ol><li>Use of blood group O-packed RBCs for transfusion</li><ol type="a"> <li>Can be transfused into any patient, regardless of the blood group</li><ul> <li>(1) Blood group O RBCs lack A and B antigens.</li><li>(2) Blood group O individuals are considered universal donors.
<blockquote style="color: blue; ">Blood group O individuals: universal donors</blockquote></li><ul> <li>Anti-A-IgM and anti-B-IgM cannot hemolyze O RBCs.</li> </ul> </ul> </ol><li>Blood group AB individuals can be transfused with blood from any blood group.</li><ol type="a"> <li>They lack natural antibodies.</li><li>They are considered universal recipients.
<blockquote style="color: blue; ">Blood group AB individuals: universal recipients</blockquote></li> </ol> </ol>
</div></html>
![[15.III.A.Blood donors]]
<<tiddler [[15.III.A.Blood donors]]>>
![[15.III.B.Patient crossmatch]]
<<tiddler [[15.III.B.Patient crossmatch]]>>
![[15.III.C.Blood component therapy (Table 15-1)]]
<<tiddler [[15.III.C.Blood component therapy (Table 15-1)]]>>
![[15.III.D.Transfusion reactions]]
<<tiddler [[15.III.D.Transfusion reactions]]>>
<html><a name="HC015018"></a><span>[[Table 15-1|Table 15-1. BLOOD COMPONENTS]]</span> <br> <br> </html>
<html><a name="HC015019"></a> <br><a name="PB015006"></a><div class="BB" style="color: rgb(47, 79, 79); ">Individuals who are <b>deficient in IgA</b> and who have antibodies directed against IgA from previous exposure to a blood product may develop a severe anaphylactic reaction. IgA-deficient individuals must receive blood or blood products that lack IgA.
<blockquote style="color: blue; ">IgA deficient patients: must receive IgA deficient blood products</blockquote></div><a name="PB015007"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Anti-HLA antibodies</b> develop when individuals are exposed to foreign HLA antigens (e.g., previous blood transfusion or organ transplant). Women commonly have these reactions owing to pregnancy, when there is an increased risk for exposure to fetal blood during delivery or after a spontaneous abortion.
<blockquote style="color: blue; ">Anti-HLA antibodies: come from previous exposure to HLA antigens (blood transfusion, transplant)</blockquote></div><a name="PB015008"></a><div class="BB" style="color: rgb(47, 79, 79); ">Individuals who have been infused with blood in the past may have been exposed to a foreign blood group antigen and developed atypical antibodies that are no longer circulating; therefore, the pretransfusion antibody screen is negative. However, memory B cells are present and reexposure to the foreign antigen causes them to produce antibodies, resulting in an extravascular hemolytic anemia. This reaction may occur within hours to 3 to 10 days after the transfusion.</div><a name="P015018"></a><div class="PA" style="color: black; "><ol type="1"> <li>Allergic reaction
<blockquote style="color: blue; ">Allergic transfusion reaction: IgE-mediated</blockquote></li><ol type="a"> <li>Most common transfusion reaction</li><li>Type I IgE-mediated hypersensitivity reaction against proteins in the donor blood</li><li>Clinical findings</li><ul> <li>(1) Urticaria with pruritus</li><li>(2) Fever, tachycardia, wheezing</li><li>(3) Potential for anaphylactic shock</li><li>(4) Mild cases are treated with antihistamines.</li> </ul> </ol><li>Febrile reaction</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Recipient has anti-human leukocyte antigen (HLA) antibodies directed against foreign HLA antigens on donor leukocytes (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>).
<blockquote style="color: blue; ">Febrile transfusion reaction: anti-HLA antibodies against donor leukocytes</blockquote></li><ul> <li>There are <i>no</i> HLA antigens on RBCs.</li> </ul><li>(2) Type II hypersensitivity reaction</li> </ul><li>Clinical findings</li><ul> <li>(1) Fever, chills, headache, and flushing</li><li>(2) Treated with antipyretics</li> </ul> </ol><li>Acute hemolytic transfusion reaction (HTR)</li><ol type="a"> <li>May be intravascular or extravascular hemolytic reactions (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)
<blockquote style="color: blue; ">Acute HTRs are due to blood group incompatibility or presence of an atypical antibody.</blockquote></li><li>Intravascular hemolysis</li><ul> <li>(1) ABO blood group incompatibility</li><li>(2) Example-group B patient receives group A donor blood.</li><ul> <li>Anti-A-IgM attaches to A positive donor RBCs producing intravascular hemolysis; type II hypersensitivity reaction
<blockquote style="color: blue; ">Acute HTRs: intravascular or extravascular hemolysis</blockquote></li> </ul> </ul><li>Extravascular hemolysis</li><ul> <li>(1) An atypical antibody reacts with a foreign antigen on donor RBCs.</li><ul> <li>(a) Recipient's splenic macrophages will phagocytose and destroy donor RBCs coated by the atypical antibody</li><li>(b) Type II hypersensitivity reaction</li> </ul><li>(2) Jaundice commonly occurs.</li><ul> <li>Unconjugated bilirubin is the end-product of macrophage degradation of hemoglobin (Hb).</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Fever</li><li>(2) Back pain</li><li>(3) Hypotension</li> </ul><li>Potential complications</li><ul> <li>(1) Disseminated intravascular coagulation</li><li>(2) Acute renal failure</li> </ul><li>Laboratory findings</li><ul> <li>(1) Positive direct Coombs' test</li><ul> <li>IgG antibody or C3b is coating donor RBCs.</li> </ul><li>(2) Positive indirect Coombs' test</li><ul> <li>Atypical antibody is present in serum.</li> </ul><li>(3) <i>No</i> significant increase in Hb over pretransfusion levels</li><li>(4) Hemoglobinuria</li><ul> <li>Sign of intravascular hemolysis (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li> </ul><li>(5) Jaundice</li><ul> <li>Sign of extravascular hemolysis</li> </ul> </ul> </ol><li>Suspected transfusion reactions
<blockquote style="color: blue; ">Suspected HTRs: keep IV open with normal saline; discontinue transfusion</blockquote></li><ol type="a"> <li>Immediately stop the blood transfusion</li><li>Keep the intravenous line in place</li><ul> <li>Keep the line open with normal saline</li> </ul><li>Send the unit of blood to the blood bank</li><li>Blood bank will do a transfusion reaction workup</li> </ol> </ol>
</div></html>
<html><a name="HC015021"></a><span>[[Fig. 15-4A|Figure 15-4]]</span> <br> <br><a name="P015020"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">ABO HDN: most common HDN</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common HDN</li><ul> <li>Present in 20% to 25% of all pregnancies</li> </ul><li>Mothers are blood group O and the fetus is either blood group A or B.
<blockquote style="color: blue; ">ABO HDN: mother group O, fetus blood group A or B</blockquote></li> </ol><li>Pathogenesis</li><ol type="a"> <li>Blood group O individuals have anti-A and B-IgG antibodies.</li><ul> <li>(1) IgG antibodies cross the placenta and attach to fetal A or B RBCs.</li><li>(2) Fetal splenic macrophages phagocytose RBCs, causing a mild anemia.</li><li>(3) Unconjugated bilirubin from extravascular hemolysis is disposed of in the mother's liver.</li> </ul><li>May affect the firstborn or any future pregnancy if ABO incompatibility exists</li> </ol><li>Clinical and laboratory findings
<blockquote style="color: blue; ">Jaundice in first 24 hours: most common cause is ABO HDN</blockquote></li><ol type="a"> <li>Jaundice develops within the first 24 hours after birth.</li><ul> <li>(1) ABO HDN is the most common cause of jaundice in this period.</li><ul> <li>Newborn liver cannot handle the excess bilirubin load.</li> </ul><li>(2) Risk for kernicterus is very small (see later).</li> </ul><li>Anemia</li><ul> <li>(1) Mild normocytic anemia or no anemia at all</li><li>(2) Exchange transfusions are rarely indicated.</li> </ul><li>Positive direct Coombs' test on fetal cord blood RBCs
<blockquote style="color: blue; ">ABO HDN: positive direct Coombs' test on fetal cord RBCs</blockquote></li><ul> <li>Due to anti-A or B-IgG antibodies coating fetal A or B RBCs</li> </ul><li>Spherocytes are present in the cord blood peripheral smear.</li><ul> <li>Due to macrophage removal of a portion of the RBC membrane</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC015022"></a><span>[[Fig. 15-4B|Figure 15-4]]</span> <br> <br><a name="PB015009"></a><div class="BB" style="color: rgb(47, 79, 79); ">Kernicterus refers to deposition of free (not bound to albumin) lipid-soluble unconjugated bilirubin in the basal ganglia owing to an incompletely formed blood-brain barrier. Bilirubin damages neurons in the brain, causing severe dysfunction.</div><a name="PB015010"></a><div class="BB" style="color: rgb(47, 79, 79); ">ABO incompatibility protects the mother from developing Rh sensitization. For example, in a mother who is O negative and carrying a fetus who is A positive, any A positive fetal RBCs entering her circulation will be destroyed by maternal anti-A-IgM antibodies, thereby preventing sensitization.
<blockquote style="color: blue; ">ABO incompatibility: protects mother from Rh sensitization</blockquote></div><a name="PB015011"></a><div class="BB" style="color: rgb(47, 79, 79); ">Special tests are performed on the mother's blood that detect fetal RBCs in her blood. The amount of fetal blood is quantified so that the appropriate amount of anti-D globulin is given to the mother. Anti-D globulin masks the antigenic sites on the fetal RBCs or destroys the fetal RBCs so that the mother does <i>not</i> host an antibody response against the D antigen. If the patient develops anti-D antibodies, there is no indication for giving the globulin either during or after delivery, because its main purpose is to prevent sensitization.</div><a name="P015021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Mother is Rh (D antigen) negative and the fetus is Rh positive.
<blockquote style="color: blue; ">Rh HDN: mother Rh negative, fetus Rh positive</blockquote></li><li>Mother is exposed to fetal Rh positive blood (fetomaternal bleed).</li><ul> <li>(1) Occurs during the last trimester or during childbirth itself</li><li>(2) Cytotrophoblast is absent during the last trimester.</li><ul> <li>Increases the risk for a fetomaternal bleed</li> </ul> </ul><li>Mother develops anti-D-IgG antibodies when exposed to fetal Rh positive cells.</li><ul> <li>First Rh incompatible pregnancy does <i>not</i> affect the firstborn.</li> </ul><li>Subsequent Rh incompatible pregnancies result in extravascular hemolytic anemia in the fetus.
<blockquote style="color: blue; ">Rh HDN: anemia and amount of unconjugated bilirubin > ABO HDN</blockquote></li><ul> <li>(1) Anti-D-IgG antibodies cross the placenta and attach to fetal Rh positive RBCs.</li><li>(2) Fetal splenic macrophages phagocytose RBCs, causing severe anemia.</li><ul> <li>(a) Fetus may develop high-output cardiac failure leading to hydrops fetalis and death.</li><li>(b) Hydrops fetalis is a combined left- and right-sided heart failure with ascites and edema.</li><li>(c) Extramedullary hematopoiesis is present in the liver and spleen.</li><li>(d) Unconjugated bilirubin is conjugated in the mother's liver.</li> </ul> </ul> </ol><li>Clinical and laboratory findings</li><ol type="a"> <li>Degree of anemia is more severe than with ABO HDN.</li><li>Jaundice develops shortly after birth.</li><ul> <li>(1) Level of unconjugated bilirubin is much higher than with ABO HDN.
<blockquote style="color: blue; ">Rh HDN: unconjugated bilirubin is free (not bound)</blockquote></li><ul> <li>Most of the unconjugated bilirubin is <i>not</i> bound by albumin and circulates free in the blood.</li> </ul><li>(2) Increased risk for kernicterus
<blockquote style="color: blue; ">Kernicterus: free unconjugated bilirubin deposits in basal ganglia</blockquote></li><ul> <li>The free, unbound lipid-soluble unconjugated bilirubin poses the greatest risk for bilirubin entry into the brain (<span>[[Fig. 15-5|Figure 15-5]]</span>).</li> </ul> </ul><li>Positive direct and indirect Coombs' tests on fetal cord blood
<blockquote style="color: blue; ">Rh HDN: positive direct Coombs' test on fetal RBCs</blockquote></li><li>Spherocytes are <i>not</i> present in cord blood.</li><ul> <li>Macrophages phagocytose the entire RBC.</li> </ul><li>Exchange transfusions are required.</li><ul> <li>(1) Newborn's blood is removed and replaced with fresh blood.</li><li>(2) Transfusion corrects anemia and removes antibodies and unconjugated bilirubin.</li> </ul> </ol><li>Prevention of Rh HDN in Rh negative mothers without anti-D</li><ol type="a"> <li>Receive anti-D globulin (Rh immune globulin) during the 28th week of pregnancy
<blockquote style="color: blue; ">Prevention of Rh HDN: Rh immune globulin (anti-D globulin)</blockquote></li><li>Anti-D globulin does <i>not</i> cross the placenta.</li><li>Anti-D globulin protects the mother from sensitization to fetal Rh positive cells that may enter her circulation during the last trimester.</li><li>Anti-D globulin lasts ∼3 months in the mother's blood.</li><li>Additional anti-D globulin is given to the mother after delivery if the baby is Rh positive.</li> </ol><li>Tests performed on sensitized (anti-D positive) women</li><ol type="a"> <li>Women are followed with sequential antibody titers and periodic amniocentesis.</li><li>Amniotic fluid is submitted to spectrophotometric analysis to identify bilirubin pigment.
<blockquote style="color: blue; ">Bilirubin absorbance: 450 nm</blockquote></li><ul> <li>(1) Bilirubin has absorbance at a wavelength of 450 nm.</li><li>(2) A Δ OD 450 value is obtained on the fluid.</li><ul> <li>Height of the bilirubin spike on the spectrophotometer reading from the baseline.</li> </ul><li>(3) Δ OD 450 is sequentially plotted on a Liley chart.
<blockquote style="color: blue; ">Δ OD 450: bilirubin wavelength in amniotic fluid; degree of increase correlates with severity of hemolysis</blockquote></li><ul> <li>Correlates Δ OD 450 with gestational age of the fetus</li> </ul><li>(4) Graph provides an indication of the degree of severity of the RBC hemolysis.</li><li>(5) Very severe cases at an early gestational age may require an in-utero exchange transfusion.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC015023"></a> <br><a name="P015022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Used as a treatment of jaundice in the newborn
<blockquote style="color: blue; ">Blue fluorescent light: converts bilirubin in skin to water-soluble dipyrrole</blockquote></li><li>Unconjugated bilirubin in the skin absorbs light energy from blue fluorescent light.</li><li>Photoisomerization converts unconjugated bilirubin to a nontoxic water-soluble dipyrrole (called lumirubin).</li><ul> <li>Lumirubin is excreted in bile or urine.</li> </ul> </ol>
</div></html>
![[15.IV.A.ABO HDN (Fig. 15-4A)]]
<<tiddler [[15.IV.A.ABO HDN (Fig. 15-4A)]]>>
![[15.IV.B.Rh HDN (Fig. 15-4B)]]
<<tiddler [[15.IV.B.Rh HDN (Fig. 15-4B)]]>>
![[15.IV.C.Use of blue fluorescent light]]
<<tiddler [[15.IV.C.Use of blue fluorescent light]]>>
<html><a name="HC016001"></a><span>[[16-2|Table 16-2. SIGNS OF RESPIRATORY DISEASE]]</span> <br><span>[[Tables 16-1|Table 16-1. COMMON SYMPTOMS OF RESPIRATORY DISEASE]]</span> <br> <br> </html>
![[16.I.A.Symptoms and Signs of Respiratory Disease (Tables 16-1 and 16-2)]]
<<tiddler [[16.I.A.Symptoms and Signs of Respiratory Disease (Tables 16-1 and 16-2)]]>>
<html><a name="HC016003"></a> <br><a name="PB016001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Calculation of the <span style="font-variant:small-caps;">a</span>-a gradient</b> in a patient breathing 0.30 O<sub>2</sub> who has a P<span style="font-variant:small-caps;">co</span><sub>2</sub> of 80 mm Hg and Pa<span style="font-variant:small-caps;">o</span><sub>2</sub> of 40 mm Hg: P<span style="font-variant:small-caps;">ao</span><sub>2</sub> = 0.30 (713) - 80/0.8 = 114 mm Hg. <span style="font-variant:small-caps;">a</span>-a gradient = 114 - 40 = 74 mm Hg, which is medically significant and indicates one or more of the above-mentioned lung disorders or a right-to-left shunt in the heart.</div><a name="PB016002"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Calculation of the <span style="font-variant:small-caps;">a</span>-a gradient</b> in a patient breathing room air who has a P<span style="font-variant:small-caps;">co</span><sub>2</sub> of 80 mm Hg and Pa<span style="font-variant:small-caps;">o</span><sub>2</sub> of 40 mm Hg: P<span style="font-variant:small-caps;">ao</span><sub>2</sub> = 0.21 (713) - 80/0.8 = 50 mm Hg. <span style="font-variant:small-caps;">a</span>-a gradient = 50 - 40 = 10 mm Hg, which excludes the lung as the cause of the hypoxemia and indicates an extrapulmonary cause of hypoxemia.</div><a name="P016001"></a><div class="PA" style="color: black; "><ol type="1"> <li><span style="font-variant:small-caps;">a</span>-a gradient is the difference in the partial pressure of oxygen (P<span style="font-variant:small-caps;">o</span><sub>2</sub>) between the alveolar P<span style="font-variant:small-caps;">o</span><sub>2</sub> (P<span style="font-variant:small-caps;">ao</span><sub>2</sub>) and arterial P<span style="font-variant:small-caps;">o</span><sub>2</sub> (Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>).</li><ol type="a"> <li><span style="font-variant:small-caps;">a</span>-a gradient is normally due to a mismatch between ventilation and perfusion in the lungs.</li><ul> <li>Example-An <span style="font-variant:small-caps;">a</span>-a gradient exists when perfusion is greater than ventilation in the lower lobes.</li> </ul><li>It is useful in differentiating causes of hypoxemia (decreased Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>; refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>).
<blockquote style="color: blue; ">↑ <span style="font-variant:small-caps;">a</span>-a gradient: hypoxemia of pulmonary origin</blockquote></li><ul> <li>(1) Hypoxemia due to pulmonary causes increases <span style="font-variant:small-caps;">a</span>-a gradient.</li><li>(2) Hypoxemia due to extrapulmonary causes has a normal <span style="font-variant:small-caps;">a</span>-a gradient.
<blockquote style="color: blue; ">Normal <span style="font-variant:small-caps;">a</span>-a gradient: hypoxemia of extrapulmonary origin</blockquote></li> </ul> </ol><li>Calculation of the <span style="font-variant:small-caps;">a</span>-a gradient</li><ol type="a"> <li>P<span style="font-variant:small-caps;">ao</span><sub>2</sub> = % O<sub>2</sub> (713) - arterial P<span style="font-variant:small-caps;">co</span><sub>2</sub>/0.8
<blockquote style="color: blue; ">P<span style="font-variant:small-caps;">ao</span><sub>2</sub> = % O<sub>2</sub> (713) - arterial P<span style="font-variant:small-caps;">co</span><sub>2</sub>/0.8</blockquote></li><ul> <li>% O<sub>2</sub> is the percentage of O<sub>2</sub> the patient is breathing; 713 is the atmospheric pressure (760 mm Hg) minus the water vapor pressure (47 mm Hg); and 0.8 is the respiratory quotient.</li> </ul><li>Example using normal values</li><ul> <li>(1) Normal P<span style="font-variant:small-caps;">ao</span><sub>2</sub> = 0.21 (713) - 40/0.8 = 100 mm Hg</li><li>(2) Normal Pa<span style="font-variant:small-caps;">o</span><sub>2</sub> = 95 mm Hg</li><li>(3) Normal <span style="font-variant:small-caps;">a</span>-a gradient = 100 mm Hg - 95 mm Hg = 5 mm Hg</li><li>(4) Medically significant <span style="font-variant:small-caps;">a</span>-a gradient ≥ 30 mm Hg
<blockquote style="color: blue; "><span style="font-variant:small-caps;">a</span>-a ≥ 30 mm Hg</blockquote></li><ul> <li>(a) <span style="font-variant:small-caps;">a</span>-a gradient normally increases with age.</li><li>(b) <span style="font-variant:small-caps;">a</span>-a ≥ 30 mm Hg is set for highest specificity.</li> </ul> </ul> </ol><li>Causes of hypoxemia with an increased <span style="font-variant:small-caps;">a</span>-a gradient (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)
<blockquote style="color: blue; ">Hypoxemia + ↑ <span style="font-variant:small-caps;">a</span>-a: ventilation, perfusion, diffusion defects; right-to-left cardiac shunts</blockquote></li><ol type="a"> <li>Ventilation defect</li><ul> <li>(1) Impaired O<sub>2</sub> delivery to the alveoli for gas exchange</li><li>(2) Example-airway collapse due to the respiratory distress syndrome</li> </ul><li>Perfusion defect</li><ul> <li>(1) Decreased or absent blood flow to the alveoli</li><li>(2) Example-pulmonary embolus</li> </ul><li>Diffusion defect</li><ul> <li>(1) O<sub>2</sub> cannot diffuse through the alveolar-capillary interface.</li><li>(2) Examples-interstitial fibrosis, pulmonary edema</li> </ul><li>Right-to-left cardiac shunt</li><ul> <li>Example-tetralogy of Fallot</li> </ul> </ol><li>Causes of hypoxemia with a normal <span style="font-variant:small-caps;">a</span>-a gradient
<blockquote style="color: blue; ">Hypoxemia + normal <span style="font-variant:small-caps;">a</span>-a: depress respiratory center, upper airway obstruction, chest bellows disease</blockquote></li><ol type="a"> <li>Depression of the respiratory center in the medulla</li><ul> <li>Examples-barbiturates, brain injury</li> </ul><li>Upper airway obstruction</li><ul> <li>(1) Epiglottitis due to <i>Haemophilus influenzae</i></li><li>(2) Croup due to parainfluenza virus</li><ul> <li>Mucosal edema narrows the trachea.</li> </ul> </ul><li>Chest bellows (muscles of respiration) dysfunction</li><ul> <li>(1) Paralyzed diaphragm</li><li>(2) Amyotrophic lateral sclerosis with degeneration of anterior horn cells</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC016004"></a><span>[[Fig. 16-1|Figure 16-1]]</span> <br> <br><a name="P016002"></a><div class="PA" style="color: black; "><ul> <li>Useful in distinguishing restrictive from obstructive lung disease</li><ol type="1"> <li>Volumes and capacities that are <i>not</i> directly measured by spirometry</li><ol type="a"> <li>Functional residual capacity (FRC)</li><ul> <li>Total amount of air in the lungs at the end of a normal expiration</li> </ul><li>Total lung capacity (TLC)</li><ul> <li>Total amount of air in a fully expanded lung</li> </ul><li>Residual volume (RV)</li><ul> <li>Volume of air left over in the lung after maximal expiration
<blockquote style="color: blue; ">Volumes <i>not</i> directly measured by spirometry: TLC, FRC, RV</blockquote></li> </ul> </ol><li>Tidal volume (TV)</li><ul> <li>Volume of air that enters or leaves the lungs during normal quiet respiration</li> </ul><li>Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV<sub>1 sec</sub>), and FEV<sub>1 sec</sub>/FVC</li><ol type="a"> <li>FVC is the total amount of air expelled after a maximal inspiration.</li><ul> <li>Normal FVC is 5 L (see <span>[[Fig. 16-1A|Figure 16-1]]</span>).</li> </ul><li>Forced expiratory volume in 1 second (FEV<sub>1 sec</sub>)</li><ul> <li>(1) Amount of air expelled from the lungs in 1 second after a maximal inspiration</li><li>(2) Normal FEV<sub>1 sec</sub> is 4 L (see <span>[[Fig. 16-1A|Figure 16-1]]</span>).
<blockquote style="color: blue; ">Normal FEV<sub>1 sec</sub>/FVC: 4-5 L</blockquote></li> </ul><li>Ratio of FEV<sub>1 sec</sub>/FVC is normally 4/5, or 80%.</li> </ol><li>Expiratory reserve volume (ERV)</li><ol type="a"> <li>ERV refers to the amount of air forcibly expelled at the end of a normal expiration.</li><li>ERV is commonly used to calculate residual volume (FRC - ERV = RV).
<blockquote style="color: blue; ">FRC - ERV = RV</blockquote></li> </ol><li>Comparison of pulmonary function tests in restrictive and obstructive lung disease (<span>[[Table 16-3|Table 16-3. COMPARISON OF PULMONARY FUNCTION TESTS IN RESTRICTIVE AND OBSTRUCTIVE LUNG DISEASE]]</span>)</li> </ol> </ul>
</div></html>
<html><a name="HC016005"></a> <br><a name="P016003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Plot of inspiratory and expiratory flow rate (liters/second) versus lung volume (liters)</li><ul> <li>Patient takes a maximal inspiration followed by a maximal expiration.</li> </ul><li>Loop consists of an inspiration curve and an expiration curve (<span>[[Fig. 16-2|Figure 16-2]]</span>).</li><ol type="a"> <li>Maximal inspiration</li><ul> <li>Begins at point A (RV) and extends to point B (TLC)
<blockquote style="color: blue; ">TLC and RV: TLC end of maximal inspiration; RV end of maximal expiration</blockquote></li> </ul><li>Maximal expiration</li><ul> <li>(1) Extends from point B to point C (peak expiratory flow, PEF) and then trails off back to point A</li><li>(2) PEF occurs early in expiratory phase of the loop (point B to C).</li><ul> <li>Due to elastic recoil of the lungs into airways with low resistance and large caliber</li> </ul><li>(3) Flow rate becomes linear from point C to A.</li><ul> <li>Encounters increased resistance in the small airways</li> </ul><li>(4) Volume of air in liters between points A and B is the vital capacity (VC).</li> </ul> </ol><li>Flow-volume loop in obstructive lung disease (<span>[[Fig. 16-3A|Figure 16-3]]</span>)</li><ol type="a"> <li>TLC is increased (e.g., ∼8.5 L) and RV is increased (e.g., 4 L).</li><ul> <li>Expiratory curve is shifted to the left of the normal curve.
<blockquote style="color: blue; ">Obstructive pattern: nonuniform emptying; expiratory curve shift to left of normal curve</blockquote></li> </ul><li>Decreased PEF</li><li>Nonuniform emptying of the airways</li><ul> <li>Concave configuration of the curve (arrow) is due to mucus plugs or collapsed small airways.</li> </ul> </ol><li>Flow-volume loop findings in restrictive parenchymal disease (<span>[[Fig. 16-3B|Figure 16-3]]</span>)</li><ol type="a"> <li>TLC is decreased (e.g.,∼4 L).</li><li>RV is decreased (e.g.,∼0.3 L).
<blockquote style="color: blue; ">Restrictive parenchymal: expiratory curve shifted to right of normal curve</blockquote></li><li>Expiratory curve is shifted to the right of the normal curve.</li><ul> <li>Expiratory curve is narrow because of decreased lung volumes.</li> </ul> </ol> </ol>
</div></html>
![[16.II.A.Calculation of the alveolar-arterial (a-a) gradient]]
<<tiddler [[16.II.A.Calculation of the alveolar-arterial (a-a) gradient]]>>
![[16.II.B.Spirometry (Fig. 16-1)]]
<<tiddler [[16.II.B.Spirometry (Fig. 16-1)]]>>
![[16.II.C.Flow-volume loop]]
<<tiddler [[16.II.C.Flow-volume loop]]>>
<html><a name="HC016007"></a> <br><a name="P016007"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Choanal atresia: newborn cannot breathe through the nose; cyanosis when breast-feeding</blockquote>
<ol type="1"> <li>Unilateral or bilateral bony septum between the nose and the pharynx</li><li>Newborn turns cyanotic when breast-feeding.</li><ul> <li>Crying causes the child to "pink up" again.</li> </ul> </ol>
</div></html>
<html><a name="HC016008"></a> <br><a name="P016008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Nasal polyps are non-neoplastic tumefactions (<span>[[Fig. 16-4|Figure 16-4]]</span>).</li><ul> <li>Develop as a response to chronic inflammation</li> </ul><li>Allergic polyps
<blockquote style="color: blue; ">Allergic polyp: most common polyp; adults</blockquote></li><ol type="a"> <li>Most common polyp</li><li>Most often seen in adults with a history of IgE-mediated allergies</li> </ol><li>Nasal polyps are associated with aspirin and other nonsteroidal drugs.</li><ol type="a"> <li>Epidemiology
<blockquote style="color: blue; ">Triad asthma: aspirin, nasal polyp, asthma</blockquote></li><ul> <li>Most often occur in women with chronic pain syndromes</li> </ul><li>Pathogenesis</li><ul> <li>(1) Drugs block cyclooxygenase leaving the lipoxygenase pathway open.</li><li>(2) Leukotrienes (LT) C-D-E<sub>4</sub> are increased, causing bronchoconstriction.
<blockquote style="color: blue; ">Nasal polyps in child: order a sweat test to rule out cystic fibrosis</blockquote></li> </ul><li>Clinical triad-nonsteroidal drugs, asthma, and nasal polyps</li> </ol><li>Nasal polyps are often associated with cystic fibrosis.</li> </ol>
</div></html>
<html><a name="HC016009"></a> <br><a name="P016009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Excessive snoring with intervals of breath cessation (apnea)
<blockquote style="color: blue; ">OSA: excessive with periods of apnea</blockquote></li><li>Causes</li><ul> <li>(1) Obesity (very common)</li><ul> <li>Pharyngeal muscles collapse due to the weight of tissue in the neck.</li> </ul><li>(2) Tonsillar hypertrophy, nasal septum deviation</li> </ul> </ol><li>Pathogenesis</li><ul> <li>Airway obstruction causes CO<sub>2</sub> retention, leading to hypoxemia.</li> </ul><li>Clinical findings</li><ol type="a"> <li>Excessive snoring with episodes of apnea</li><li>Daytime somnolence often simulating narcolepsy</li> </ol><li>Laboratory findings</li><ol type="a"> <li>Decreased P<span style="font-variant:small-caps;">o</span><sub>2</sub> and O<sub>2</sub> saturation during apneic episodes</li><li>Increase in arterial P<span style="font-variant:small-caps;">co</span><sub>2</sub> (respiratory acidosis)
<blockquote style="color: blue; ">OSA: apnea causes respiratory acidosis and hypoxemia</blockquote></li> </ol><li>Complications</li><ol type="a"> <li>Pulmonary hypertension (PH) leading to right ventricular hypertrophy</li><ul> <li>Called cor pulmonale (see section VII)
<blockquote style="color: blue; ">OSA: risk for developing cor pulmonale</blockquote></li> </ul><li>Secondary polycythemia</li><ul> <li>Due to a hypoxemic stimulus for erythropoietin release</li> </ul> </ol><li>Polysomnography
<blockquote style="color: blue; ">Polysomnography: confirmatory test for OSA</blockquote></li><ul> <li>Confirmatory test that documents periods of apnea during sleep</li> </ul><li>Treatment</li><ol type="a"> <li>Nasal continuous positive airway pressure (CPAP)</li><li>Surgical correction of any obstructive lesions, weight loss</li> </ol> </ol>
</div></html>
<html><a name="HC016010"></a> <br><a name="P016010"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Sinus infections: maxillary in adults, ethmoid in children</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Maxillary sinus is most often involved in adults.</li><li>Ethmoid sinus is most often involved in children.</li><li>Causes</li><ul> <li>(1) Upper respiratory infections (URIs); e.g., viral, bacterial</li><ul> <li>Block drainage of sinuses into nasal cavity
<blockquote style="color: blue; ">Viral URI: most common cause of sinusitis</blockquote></li> </ul><li>(2) Deviated nasal septum</li><li>(3) Allergic rhinitis</li><li>(4) Barotrauma</li><li>(5) Smoking cigarettes</li> </ul><li>Pathogens causing sinusitis</li><ul> <li>(1) Rhinoviruses</li><li>(2) <i>Streptococcus pneumoniae</i> (most common)
<blockquote style="color: blue; "><i>Streptococcus pneumoniae:</i> most common bacterial pathogen causing sinusitis</blockquote></li><li>(3) Anaerobes (chronic sinusitis)</li><li>(4) Systemic fungi (e.g., <i>Mucor</i> or <i>Aspergillus</i> species)</li><ul> <li>Diabetics commonly have sinusitis due to <i>Mucor</i> species.</li> </ul> </ul> </ol><li>Pathogenesis</li><ul> <li>Blockage of sinus drainage into the nasal cavity
<blockquote style="color: blue; ">Sinusitis: blockage of sinus drainage in nasal cavity</blockquote></li> </ul><li>Clinical findings</li><ol type="a"> <li>Fever</li><li>Nasal congestion</li><li>Pain over sinuses</li><li>Postnasal drip</li> </ol><li>Diagnosis</li><ol type="a"> <li>Gold standard for bacterial culture is sinus aspiration</li><li>Sinus radiographs</li><li>CT scan is the most sensitive test.
<blockquote style="color: blue; ">Sinusitis: CT scan most sensitive</blockquote></li><ul> <li>Recommended if surgery is an option</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Decongestants</li><li>Antimicrobial therapy</li><ul> <li>(1) Recommendation is <i>not</i> to use antibiotics.</li><ul> <li>Most cases are viral and resolve within 2 weeks</li> </ul><li>(2) If resolution does <i>not</i> occur, antibiotics often used include the following:</li><ul> <li>Amoxicillin (most common drug), erythromycin, trimethoprim-sulfamethoxazole (TMP/SMX)</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC016011"></a> <br><a name="P016011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common malignant tumor of the nasopharynx</li><li>Male dominant</li><li>Increased incidence in the Chinese and African populations</li> </ol><li>Pathogenesis
<blockquote style="color: blue; ">Nasopharyngeal carcinoma: association with EBV</blockquote></li><ul> <li>Causal relationship with Epstein-Barr virus (EBV)</li> </ul><li>Pathologic findings</li><ol type="a"> <li>Squamous cell carcinoma or undifferentiated cancer</li><li>Metastasizes to cervical lymph nodes</li> </ol> </ol>
</div></html>
<html><a name="HC016012"></a> <br><a name="P016012"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>More common in men than in women</li><li>Risk factors
<blockquote style="color: blue; ">Laryngeal carcinoma: cigarette smoking is the most common cause</blockquote></li><ul> <li>(1) Cigarette smoking (most common cause)</li><li>(2) Alcohol (synergistic effect with smoking)</li><li>(3) Squamous papillomas and papillomatosis</li><ul> <li>Human papillomavirus type 6 and 11 association</li> </ul> </ul><li>Majority are located on the true vocal cords (<span>[[Fig. 16-5|Figure 16-5]]</span>).
<blockquote style="color: blue; ">Laryngeal carcinoma: most on true vocal cords; squamous cancer</blockquote></li> </ol><li>Majority are keratinizing squamous cell carcinomas.</li><li>Clinical findings</li><ul> <li>Persistent hoarseness is often associated with cervical lymphadenopathy.</li> </ul><li>Treatment is surgery.</li> </ol>
</div></html>
![[16.III.A.Choanal atresia]]
<<tiddler [[16.III.A.Choanal atresia]]>>
![[16.III.B.Nasal polyps]]
<<tiddler [[16.III.B.Nasal polyps]]>>
![[16.III.C.Obstructive sleep apnea (OSA)]]
<<tiddler [[16.III.C.Obstructive sleep apnea (OSA)]]>>
![[16.III.D.Sinusitis]]
<<tiddler [[16.III.D.Sinusitis]]>>
![[16.III.E.Nasopharyngeal carcinoma]]
<<tiddler [[16.III.E.Nasopharyngeal carcinoma]]>>
![[16.III.F.Laryngeal carcinoma]]
<<tiddler [[16.III.F.Laryngeal carcinoma]]>>
<html><a name="HC016014"></a> <br><a name="P016015"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Airway obstruction by thick secretions prevents air from reaching the alveoli.
<blockquote style="color: blue; ">Resorption atelectasis: most common cause of fever 24 to 36 hours after surgery</blockquote></li><ul> <li>Obstruction occurs in bronchi, segmental bronchi, or terminal bronchioles.</li> </ul><li>Causes of obstruction</li><ul> <li>(1) Mucus or mucopurulent plug after surgery</li><li>(2) Aspiration of foreign material</li><li>(3) Centrally located bronchogenic carcinoma</li> </ul><li>Cause of alveolar collapse</li><ul> <li>Lack of air and distal resorption of preexisting air through the pores of Kohn in the alveolar walls</li> </ul><li>Collapse may involve all or part of a lung.</li> </ol><li>Clinical findings</li><ol type="a"> <li>Fever and dyspnea</li><ul> <li>Both usually occur within 24 to 36 hours of collapse.</li> </ul><li>Absent breath sounds</li><li>Absent vocal vibratory sensation (tactile fremitus)
<blockquote style="color: blue; ">Resorption atelectasis: absent vibratory sensation, dullness to percussion, absent breath sounds</blockquote></li><ul> <li>Alveoli are collapsed.</li> </ul><li>Ipsilateral elevation of the diaphragm and tracheal deviation</li><ul> <li>Only occurs if large areas of the lung are atelectatic</li> </ul><li>Collapsed lung does <i>not</i> expand on inspiration (inspiratory lag).</li> </ol><li>Treatment</li><ol type="a"> <li>Incentive spirometry after surgery</li><li>Positive-pressure breathing (CPAP) by face mask</li><li>Positive end-expiratory pressure (PEEP) on mechanical ventilation</li> </ol> </ol>
</div></html>
![[16.IV.A.Resorption atelectasis]]
<<tiddler [[16.IV.A.Resorption atelectasis]]>>
![[16.IV.B.Compression atelectasis]]
<<tiddler [[16.IV.B.Compression atelectasis]]>>
![[16.IV.C.Atelectasis due to loss of surfactant]]
<<tiddler [[16.IV.C.Atelectasis due to loss of surfactant]]>>
<html><a name="HC016015"></a> <br><a name="P016016"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Compression atelectasis: air under pressure or fluid in pleural cavity</blockquote>
<ol type="1"> <li>Air or fluid in the pleural cavity under increased pressure collapses small airways beneath the pleura.</li><li>Examples</li><ol type="a"> <li>Tension pneumothorax where air compresses the lung</li><li>Pleural effusion where fluid compresses the lung</li> </ol> </ol>
</div></html>
<html><a name="HC016016"></a> <br><a name="PB016003"></a><div class="BB" style="color: rgb(47, 79, 79); ">Women who have to deliver their babies prematurely receive glucocorticoids in order to increase fetal surfactant synthesis, thereby reducing the potential for developing RDS. Good maternal glycemic control decreases the risk for RDS.
<blockquote style="color: blue; ">Fetal surfactant: ↑ with maternal intake of glucocorticoids</blockquote></div><a name="P016017"></a><div class="PA" style="color: black; "><ol type="1"> <li>Surfactant</li><ol type="a"> <li>Synthesized by type II pneumocytes
<blockquote style="color: blue; ">Surfactant: synthesized in type II pneumocytes</blockquote></li><ul> <li>(1) Stored in lamellar bodies (<span>[[Fig. 16-6|Figure 16-6]]</span>)</li><li>(2) Synthesis begins in 28th week of gestation.</li> </ul><li>Phosphatidylcholine (lecithin) is the major component.</li><li>Synthesis is increased by cortisol and thyroxine.</li><li>Synthesis is decreased by insulin.
<blockquote style="color: blue; ">Surfactant: cortisol increases synthesis, insulin inhibits synthesis</blockquote></li><li>Surfactant reduces surface tension in the small airways.</li><ul> <li>Prevents collapse on expiration, when collapsing pressure is greatest
<blockquote style="color: blue; ">Surfactant: ↓ surface tension</blockquote></li> </ul> </ol><li>Respiratory distress syndrome (RDS) in newborns</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Decreased surfactant in the fetal lungs; causes:
<blockquote style="color: blue; ">RDS: due to a decrease in surfactant</blockquote></li><ul> <li>(a) Prematurity</li><li>(b) Maternal diabetes
<blockquote style="color: blue; ">RDS: prematurity, diabetes, C-section</blockquote></li><ul> <li>Fetal hyperglycemia increases insulin release.</li> </ul><li>(c) Cesarean section</li><ul> <li>Lack of stress-induced increase in cortisol from a vaginal delivery</li> </ul> </ul><li>(2) Widespread atelectasis results in massive intrapulmonary shunting.
<blockquote style="color: blue; ">RDS: intrapulmonary shunting</blockquote></li><ul> <li>Perfusion without ventilation</li> </ul> </ul><li>Collapsed alveoli are lined by hyaline membranes (<span>[[Fig. 16-7|Figure 16-7]]</span>).</li><ul> <li>Derived from proteins leaking out of damaged pulmonary vessels</li> </ul><li>Clinical findings</li><ul> <li>(1) Respiratory difficulty begins within a few hours after birth.</li><li>(2) Grunting (see <span>[[Table 16-2|Table 16-2. SIGNS OF RESPIRATORY DISEASE]]</span>)
<blockquote style="color: blue; ">RDS: grunting, tachypnea, intercostal retractions</blockquote></li><li>(3) Tachypnea</li><li>(4) Intercostal retractions</li><li>(5) Infants develop hypoxemia and respiratory acidosis.</li> </ul><li>Diagnosis</li><ul> <li>Chest radiograph shows a "ground glass" appearance (<span>[[Fig. 16-8|Figure 16-8]]</span>).</li> </ul><li>Complications
<blockquote style="color: blue; ">RDS O<sub>2</sub> complications: blindness, bronchopulmonary dysplasia</blockquote></li><ul> <li>(1) Superoxide free radical damage from O<sub>2</sub> therapy</li><ul> <li>May result in blindness and permanent damage to small airways (bronchopulmonary dysplasia)</li> </ul><li>(2) Intraventricular hemorrhage</li><li>(3) Patent ductus arteriosus</li><ul> <li>Due to persistent hypoxemia</li> </ul><li>(4) Necrotizing enterocolitis</li><ul> <li>Intestinal ischemia allows entry of gut bacteria into the intestinal wall.</li> </ul><li>(5) Hypoglycemia in newborn
<blockquote style="color: blue; ">Hypoglycemia in newborn: due to excess insulin in response to fetal hyperglycemia</blockquote></li><ul> <li>(a) Excess insulin decreases serum glucose, producing seizures and damage to neurons.</li><li>(b) Must give newborns glucose to prevent hypoglycemia</li> </ul> </ul><li>Treatment</li><ul> <li>CPAP therapy with endotracheal tube with O<sub>2</sub> and surfactant</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC016038"></a> <br><a name="P016054"></a><div class="PA" style="color: black; "><ol type="1"> <li>Permanent enlargement of all or part of the respiratory unit
<blockquote style="color: blue; ">Emphysema: targets the respiratory unit</blockquote></li><ul> <li>Respiratory bronchioles, alveolar ducts, alveoli</li> </ul><li>Epidemiology</li><ol type="a"> <li>Causes</li><ul> <li>(1) Cigarette smoking is the most common cause.
<blockquote style="color: blue; ">Cigarette smoking: most common cause of emphysema</blockquote></li><li>(2) α<sub>1</sub>-Antitrypsin (AAT) deficiency</li> </ul><li>Types of emphysema associated with smoking or loss of AAT</li><ul> <li>(1) Centriacinar (centrilobular) emphysema</li><li>(2) Panacinar emphysema</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Increased compliance and decreased elasticity
<blockquote style="color: blue; ">Emphysema: ↑ compliance, ↓ elasticity</blockquote></li><ul> <li>(1) Imbalance between elastase and anti-elastases (e.g., AAT)</li><li>(2) Imbalance between oxidants (free radicals) and antioxidants (e.g., glutathione)</li><li>(3) Elastase and oxidants derive from neutrophils and macrophages.</li><li>(4) Net effect of the preceding is destruction of elastic tissue.
<blockquote style="color: blue; ">Cigarette smoke: chemotactic to neutrophils; inactivates AAT and glutathione</blockquote></li> </ul><li>Cigarette smoke is chemotactic to neutrophils and macrophages.</li><ul> <li>They accumulate in the respiratory unit and release free radicals and elastases.</li> </ul><li>Free radicals in cigarette smoke inactivate AAT and antioxidants.</li><ul> <li>Produces a functional AAT deficiency</li> </ul><li>Normal function of elastic tissue</li><ul> <li>(1) Fibers attach to the outside wall of the small airways (<span>[[Fig. 16-23A|Figure 16-23]]</span>).</li><li>(2) Fibers apply radial traction to keep the airway lumens open.</li> </ul><li>Destruction of elastic tissue causes loss of radial traction.
<blockquote style="color: blue; ">Destruction of elastic tissue: loss of radial traction</blockquote></li><ul> <li>Small airways collapse, particularly on expiration.</li> </ul><li>Sites of elastic tissue destruction in emphysema</li><ul> <li>(1) Distal terminal bronchiole at its junction with the respiratory bronchiole (RB)</li><li>(2) All or part of the respiratory unit</li> </ul><li>Site of obstruction and air trapping in emphysema</li><ul> <li>(1) During expiration, the distal terminal bronchioles collapse preventing egress of air out of the respiratory unit.</li><li>(2) Trapped air distends parts of the respiratory unit that have lost their elastic tissue support.
<blockquote style="color: blue; ">Air trapping behind collapsed distal terminal bronchioles</blockquote></li> </ul> </ol><li>Centriacinar (centrilobular) emphysema (<span>[[Fig. 16-23B|Figure 16-23]]</span>)</li><ol type="a"> <li>Epidemiology</li><ul> <li>Most common type of emphysema in smokers</li> </ul><li>Pathogenesis</li><ul> <li>(1) Primarily involves the apical segments of the upper lobes
<blockquote style="color: blue; ">Centriacinar emphysema: destruction of the distal terminal bronchioles and RBs; upper lobe</blockquote></li><li>(2) Distal terminal bronchioles and the RBs (<span>[[Fig. 16-24|Figure 16-24]]</span>) are the sites of elastic tissue destruction.</li><li>(3) Air trapped behind the collapsed distal terminal bronchioles distends the RBs.</li><ul> <li>The trapped air increases RV and TLC.</li> </ul> </ul> </ol><li>Panacinar emphysema (see <span>[[Fig. 16-22C|Figure 16-22]]</span>)</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Associated with AAT deficiency</li><ul> <li>Genetic or acquired causes (cigarette smoke inactivates AAT)</li> </ul><li>(2) Genetic type of AAT deficiency</li><ul> <li>(a) Autosomal dominant</li><li>(b) MM phenotype is normal.</li><ul> <li>Normal amounts of AAT are synthesized in the liver.</li> </ul><li>(c) Homozygous ZZ type has decreased synthesis of AAT by the liver.</li> </ul><li>(3) Emphysema develops at an early age in the genetic type.</li> </ul><li>Pathogenesis</li><ul> <li>(1) Primarily affects the lower lobes
<blockquote style="color: blue; ">Panacinar emphysema: targets distal terminal bronchioles and the entire respiratory unit; lower lobe</blockquote></li><li>(2) Distal terminal bronchioles and all parts of the respiratory units are the sites of elastic tissue destruction (<span>[[Fig. 16-25|Figure 16-25]]</span>).</li><li>(3) Air trapped behind the collapsed terminal bronchioles distends the entire respiratory unit.</li> </ul><li>Laboratory finding
<blockquote style="color: blue; ">Panacinar emphysema: loss α<sub>1</sub>-globulin peak on SPE</blockquote></li><ul> <li>Absent α<sub>1</sub>-globulin peak in a serum protein electrophoresis (SPE)</li> </ul> </ol><li>Clinical findings in centriacinar and panacinar emphysema</li><ol type="a"> <li>Progressive dyspnea and hyperventilation</li><ul> <li>(1) Dyspnea is severe and occurs early in the disease.</li><li>(2) Sometimes patients are called "pink puffers."
<blockquote style="color: blue; ">Emphysema: pink puffers; blow off CO<sub>2</sub></blockquote></li> </ul><li>Centriacinar type frequently coexists with chronic bronchitis.</li><li>Breath sounds are diminished due to hyperinflation.</li><li>Cor pulmonale is uncommon.</li> </ol><li>Chest radiograph (<span>[[Fig. 16-26|Figure 16-26]]</span>)</li><ol type="a"> <li>Hyperlucent lung fields</li><li>Increased anteroposterior diameter</li><li>Vertically oriented heart</li><li>Depressed diaphragms due to hyperinflated lungs
<blockquote style="color: blue; ">Chest x-ray: hyperlucency, ↑ AP diameter, vertically oriented heart, depressed diaphragms</blockquote></li> </ol><li>Pulmonary function tests and arterial blood gases</li><ol type="a"> <li>Increased TLC due to an increase in RV</li><li>Decreased FEV<sub>1 sec</sub> (e.g., 1 L versus 4 L; see <span>[[Fig. 16-1C|Figure 16-1]]</span>)</li><li>Decreased FVC (e.g., 3 L versus 5 L; see <span>[[Fig. 16-1C|Figure 16-1]]</span>)</li><ul> <li>Decreased FEV<sub>1 sec</sub>/FVC ratio (e.g., 1/3 = 33%)
<blockquote style="color: blue; ">Emphysema: ↑TLC, RV; ↓FEV<sub>1 sec</sub>/FVC</blockquote></li> </ul><li>Decreased Pa<span style="font-variant:small-caps;">o</span><sub>2</sub> develops late in the disease.</li><ul> <li>Destruction of the capillary bed matches destruction of the respiratory unit.</li> </ul><li>Normal to decreased arterial P<span style="font-variant:small-caps;">co</span><sub>2</sub> (respiratory alkalosis)
<blockquote style="color: blue; ">Emphysema: normal to ↓arterial P<span style="font-variant:small-caps;">co</span><sub>2</sub> (respiratory alkalosis)</blockquote></li> </ol><li>Treatment</li><ol type="a"> <li>Cessation of smoking most important</li><li>Pulmonary rehabilitation program</li><li>Oxygen, using 1 to 2 L/minute, through nasal prongs</li><ul> <li>Maintain O<sub>2</sub> saturation of 90%</li> </ul><li>Bronchodilators</li><ul> <li>(1) Catecholamine inhalers/nebulizers</li><li>(2) Steroid inhalers controversial</li> </ul><li>Anticholinergics</li> </ol><li>Other types of emphysema unrelated to smoking or AAT deficiency</li><ol type="a"> <li>Paraseptal emphysema</li><ul> <li>(1) Localized disease in a subpleural location</li><ul> <li>Primarily targets the alveolar ducts and alveoli</li> </ul><li>(2) Does <i>not</i> produce obstructive airway disease</li><li>(3) Increased incidence of spontaneous pneumothorax
<blockquote style="color: blue; ">Paraseptal emphysema: risk for spontaneous pneumothorax</blockquote></li><ul> <li>Due to rupture of subpleural blebs</li> </ul> </ul><li>Irregular emphysema
<blockquote style="color: blue; ">Irregular emphysema: scar emphysema</blockquote></li><ul> <li>(1) Localized disease is associated with scar tissue.</li><li>(2) Does <i>not</i> produce obstructive airway disease</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC016039"></a> <br><a name="PB016007"></a><div class="BB" style="color: rgb(47, 79, 79); ">Turbulent airflow in the bronchi is converted to laminar airflow in the terminal (nonrespiratory) bronchioles. The terminal bronchioles undergo parallel branching, which reduces airflow resistance and spreads air out over a large cross-sectional area. Small airway disease associated with expiratory wheezing is due to narrowing of the terminal bronchioles by mucus plugs, inflammation, and fibrosis. Mucus plugs located in a proximal terminal bronchiole prevent the exodus of a large amount of CO<sub>2</sub> arising from the distally located airways producing respiratory acidosis.</div><a name="P016055"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology
<blockquote style="color: blue; ">CB: productive cough at least 3 months for 2 consecutive years</blockquote></li><ol type="a"> <li>Productive cough for at least 3 months for 2 consecutive years</li><li>Causes</li><ul> <li>(1) Smoking cigarettes
<blockquote style="color: blue; ">Smoking cigarettes: most common cause of CB</blockquote></li><li>(2) Cystic fibrosis</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Hypersecretion of mucus in bronchi</li><li>Obstruction to airflow in the terminal bronchioles</li><ul> <li>Airflow obstruction is proximal to the obstruction in emphysema.</li> </ul><li>Irreversible fibrosis of terminal bronchioles</li><li>Changes in the bronchi
<blockquote style="color: blue; ">CB: hypersecretion of mucous glands</blockquote></li><ul> <li>(1) Hypersecretion of submucosal mucus-secreting glands in trachea and bronchi</li><ul> <li>Primarily responsible for sputum overproduction</li> </ul><li>(2) Acute inflammation (neutrophils) often superimposed on chronic inflammation</li><li>(3) Loss of ciliated epithelium and presence of squamous metaplasia</li> </ul><li>Changes in the terminal bronchioles</li><ul> <li>(1) Mucus plugs in lumens (block the exodus of CO<sub>2</sub>)</li><li>(2) Goblet cell metaplasia</li><li>(3) Hypertrophy of mucus-secreting glands</li><li>(4) Chronic inflammation and fibrosis narrowing the lumen</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Productive cough</li><li>Dyspnea occurs late in the disease.</li><li>Cyanosis of skin and mucous membranes
<blockquote style="color: blue; ">CB: blue bloaters; retain CO<sub>2</sub> and develop cyanosis</blockquote></li><ul> <li>(1) Decreased O<sub>2</sub> saturation from hypoxemia (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li><li>(2) Patients are called "blue bloaters."</li> </ul><li>Tend to be stocky or obese
<blockquote style="color: blue; ">CB: stocky and obese; horizontally oriented heart</blockquote></li><li>Expiratory wheezing and sibilant rhonchi</li><li>Cor pulmonale is commonly present.</li> </ol><li>Chest radiograph</li><ol type="a"> <li>Large, horizontally oriented heart</li><li>Increased bronchial markings</li> </ol><li>Pulmonary function tests and arterial blood gases</li><ol type="a"> <li>Less increase in TLC and RV than emphysema</li><li>Chronic respiratory acidosis
<blockquote style="color: blue; ">CB: chronic respiratory acidosis and hypoxemia</blockquote></li><ul> <li>(1) Arterial P<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg</li><li>(2) Bicarbonate > 30 mEq/L
<blockquote style="color: blue; ">CB: hypoxemia early in CB</blockquote></li> </ul><li>Moderate to severe hypoxemia early in the disease</li> </ol><li>Treatment (see Emphysema)</li><li>Summary of findings in disease and emphysema (<span>[[Table 16-5|Table 16-5. COMPARISON OF EMPHYSEMA AND CHRONIC BRONCHITIS]]</span>)</li> </ol>
</div></html>
<html><a name="HC016040"></a> <br><a name="PB016008"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Ozone (O<sub>3</sub>)</b> is an air pollutant that derives from interactions of O<sub>2</sub> with oxides of nitrogen and sulfur, and hydrocarbons. It forms highly reactive free radicals in the airways that cause inflammation and irritation, often precipitating asthma.</div><a name="P016056"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Episodic and reversible airway disease (most cases)
<blockquote style="color: blue; ">Asthma: episodic and reversible airway disease</blockquote></li><li>Primarily targets the bronchi and terminal bronchioles</li><li>Most common chronic respiratory disease in children</li><ul> <li>(1) More common in children than adults</li><li>(2) Majority (50-80%) develop symptoms <i>before</i> 5 years of age</li> </ul><li>Extrinsic and intrinsic types</li> </ol><li>Extrinsic asthma
<blockquote style="color: blue; ">Extrinsic asthma: type I hypersensitivity reaction</blockquote></li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Type I hypersensitivity reaction with exposure to extrinsic allergens</li><ul> <li>Typically develops in children with an atopic family history to allergies</li> </ul><li>(2) Initial sensitization to an inhaled allergen</li><ul> <li>(a) Stimulate induction of subset 2 helper T cells (CD4 T<sub>H</sub>2) that release interleukin (IL) 4 and IL-5
<blockquote style="color: blue; ">IL-4: isotype switching to IgE production</blockquote></li><li>(b) IL-4 stimulates isotype switching to IgE production.</li><li>(c) IL-5 stimulates production and activation of eosinophils.
<blockquote style="color: blue; ">IL-5: production and activation of eosinophils</blockquote></li> </ul><li>(3) Inhaled antigens cross-link IgE antibodies on mast cells on mucosal surfaces.</li><ul> <li>(a) Release of histamine and other preformed mediators</li><li>(b) Functions of mediators</li><ul> <li>Stimulate bronchoconstriction, mucus production, influx of leukocytes</li> </ul> </ul><li>(4) Late phase reaction (4-8 hours later)</li><ul> <li>(a) Eotaxin is produced.</li><ul> <li>Chemotactic for eosinophils and activates eosinophils
<blockquote style="color: blue; ">Eosinophils: major basic protein and cationic protein damage epithelial cells</blockquote></li> </ul><li>(b) Eosinophils release major basic protein and cationic protein.</li><ul> <li>Damage epithelial cells and produce airway constriction</li> </ul> </ul> </ul><li>Other mediators involved</li><ul> <li>(1) LTC-D-E<sub>4</sub> causes prolonged bronchoconstriction.
<blockquote style="color: blue; ">LTC-D-E<sub>4</sub>: potent bronchoconstrictors</blockquote></li><li>(2) Acetylcholine causes airway muscle contraction.</li> </ul><li>Histologic changes in bronchi</li><ul> <li>(1) Thickening of the basement membrane</li><li>(2) Edema and a mixed inflammatory infiltrate</li><li>(3) Hypertrophy of submucosal glands</li><li>(4) Hypertrophy/hyperplasia of smooth muscle cells</li> </ul><li>Histologic changes in the terminal bronchioles</li><ul> <li>(1) Formation of spiral-shaped mucus plugs</li><ul> <li>(a) Contain shed epithelial cells called Curschmann spirals
<blockquote style="color: blue; ">Curschmann spirals: shed epithelial cells</blockquote></li><li>(b) Pathologic effect of major basic protein and cationic protein</li> </ul><li>(2) Crystalline granules in eosinophils coalesce to form Charcot-Leyden crystals.
<blockquote style="color: blue; ">Eosinophils: granules produce Charcot-Leyden crystals</blockquote></li><li>(3) Patchy loss of epithelial cells, goblet cell metaplasia</li><li>(4) Thick basement membrane</li><li>(5) Smooth muscle cell hypertrophy and hyperplasia</li> </ul><li>Clinical findings</li><ul> <li>(1) Episodic expiratory wheezing (inspiratory as well when severe)
<blockquote style="color: blue; ">Asthma: wheezing; ↑ anteroposterior diameter</blockquote></li><li>(2) Nocturnal cough</li><li>(3) Increased anteroposterior diameter</li><ul> <li>Due to air trapping and increase in residual volume</li> </ul> </ul><li>Laboratory findings</li><ul> <li>(1) Initially develop respiratory alkalosis
<blockquote style="color: blue; ">Bronchial asthma: initially present with respiratory alkalosis</blockquote></li><ul> <li>(a) Patients work hard at expelling air through inflamed airways.</li><li>(b) May progress into respiratory acidosis if bronchospasm is <i>not</i> relieved</li><ul> <li>Normal pH or respiratory acidosis is an indication for intubation and mechanical ventilation.
<blockquote style="color: blue; ">Bronchial asthma: normal pH or respiratory acidosis indicates need for intubation</blockquote></li> </ul> </ul><li>(2) Eosinophilia, positive skin tests for allergens</li> </ul><li>Treatment of mild disease</li><ul> <li>Metered-dose inhaler with a β<sub>2</sub>-agonist (e.g., albuterol)</li> </ul><li>Treatment of more advanced disease</li><ul> <li>(1) Metered low-dose inhaler with corticosteroids</li><li>(2) Use of leukotriene inhibitors</li> </ul> </ol><li>Intrinsic asthma
<blockquote style="color: blue; ">Intrinsic asthma: nonimmune</blockquote></li><ol type="a"> <li>Nonimmune</li><li>Causes</li><ul> <li>(1) Virus-induced respiratory infection</li><ul> <li>Examples-rhinovirus, parainfluenza virus, respiratory syncytial virus</li> </ul><li>(2) Air pollutants
<blockquote style="color: blue; ">O<sub>3</sub>: free radical; O<sub>2</sub> combining with oxides of nitrogen and sulfur</blockquote></li><li>(3) Aspirin or nonsteroidal drug sensitivity (see section III)</li><li>(4) Stress, exercise, cigarette smoke</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC016041"></a> <br><a name="P016057"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>Permanent dilation of the bronchi and bronchioles
<blockquote style="color: blue; ">Bronchiectasis: permanent dilation of bronchi and bronchioles</blockquote></li><ul> <li>Due to destruction of cartilage and elastic tissue by chronic necrotizing infections</li> </ul><li>Causes</li><ul> <li>(1) Cystic fibrosis (CF)
<blockquote style="color: blue; ">CF: most common cause of bronchiectasis</blockquote></li><ul> <li>Most common cause in the United States</li> </ul><li>(2) Infections</li><ul> <li>(a) TB is the most common cause worldwide.</li><li>(b) Adenovirus, <i>Staphylococcus aureus, Haemophilus influenzae</i></li> </ul><li>(3) Bronchial obstruction</li><ul> <li>Example-proximally located bronchogenic carcinoma occludes the lumen.</li> </ul><li>(4) Primary ciliary dyskinesia</li><ul> <li>(a) Absent dynein arm in cilia</li><li>(b) Dynein arm contains ATPase (adenosine triphosphatase) for movement of the cilia.
<blockquote style="color: blue; ">Primary ciliary dyskinesia: absent dynein arm in cilia</blockquote></li> </ul><li>(5) Allergic bronchopulmonary aspergillosis</li> </ul> </ol><li>Gross findings</li><ol type="a"> <li>Most commonly occurs in the lower lobes
<blockquote style="color: blue; ">Bronchiectasis: dilated bronchi extend to periphery</blockquote></li><li>Dilated bronchi and bronchioles are filled with pus (<span>[[Figs. 16-27|Figure 16-27]]</span> and <span>[[16-28|Figure 16-28]]</span>).</li><ul> <li>(1) Dilated airways extend to the lung periphery.</li><li>(2) Dilations are tubelike and/or saccular.</li> </ul> </ol><li>Clinical findings
<blockquote style="color: blue; ">Bronchiectasis: productive cough, hemoptysis</blockquote></li><ol type="a"> <li>Cough productive of copious sputum (often cupfuls)</li><li>Hemoptysis that is sometimes massive</li><li>Digital clubbing</li><li>Cor pulmonale</li> </ol><li>Chest radiograph findings</li><ul> <li>Crowded bronchial markings extend to the lung periphery.</li> </ul><li>CF
<blockquote style="color: blue; ">CF: autosomal recessive</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Autosomal recessive disease</li><li>(2) Primarily affects whites (>98%)</li><ul> <li>Uncommon in Asians and blacks</li> </ul><li>(3) Most common fatal hereditary disorder of whites in United States</li><li>(4) Median age of diagnosis ∼5 months</li><li>(5) Median survival age: 30 years</li> </ul><li>Pathogenesis
<blockquote style="color: blue; ">CF: 3 nucleotide deletion chromosome 7 coding for phenylalanine</blockquote></li><ul> <li>(1) Three nucleotide deletion on chromosome 7</li><ul> <li>Nucleotides normally code for phenylalanine.</li> </ul><li>(2) Production of a defective CF transmembrane conductance regulator (CFTR) for chloride ions</li><li>(3) CFTR Cl<sup>-</sup> is degraded in the Golgi apparatus.
<blockquote style="color: blue; ">CF: defective CFTR Cl<sup>-</sup> is degraded in Golgi apparatus</blockquote></li><ul> <li>Due to defective protein folding</li> </ul><li>(4) Loss of CFTR Cl<sup>-</sup> causes decreased Na<sup>+</sup> and Cl<sup>-</sup> reabsorption in sweat glands. (<span>[[Fig. 16-29A|Figure 16-29]]</span>)</li><ul> <li>Basis of the sweat test
<blockquote style="color: blue; ">CF: loss of NaCl in sweat; loss of NaCl in luminal secretions (dehydrated)</blockquote></li> </ul><li>(5) Effect of loss of CFTR Cl<sup>-</sup> in other secretions (<span>[[Fig. 16-29B|Figure 16-29]]</span>)</li><ul> <li>(a) Increased Na<sup>+</sup> and water reabsorption from luminal secretions</li><li>(b) Decreased Cl<sup>-</sup> secretion out of epithelial cells into luminal secretions</li><li>(c) Net effect is dehydration of body secretions due to lack of NaCl</li><ul> <li>Secretions are dehydrated in bronchioles, pancreatic ducts, bile ducts, meconium, and seminal fluid.</li> </ul> </ul> </ul><li>Clinical findings
<blockquote style="color: blue; ">CF: nasal polyps</blockquote></li><ul> <li>(1) Nasal polyps (25% of cases)</li><li>(2) Heat exhaustion</li><ul> <li>Loss of sodium-containing fluid from skin</li> </ul><li>(3) Respiratory infections/failure
<blockquote style="color: blue; ">Respiratory infections: most common cause of death in CF</blockquote></li><ul> <li>(a) <i>Pseudomonas aeruginosa</i> is the most common respiratory pathogen.</li><ul> <li>Other common pathogens-<i>S. aureus, H. influenzae</i></li> </ul><li>(b) Cor pulmonale commonly occurs.</li> </ul><li>(4) Pneumothorax (20%)</li><ul> <li>Rupture of blebs that develop from infection
<blockquote style="color: blue; ">CF: chronic pancreatitis producing malabsorption and type 1 diabetes</blockquote></li> </ul><li>(5) Malabsorption (80%)</li><ul> <li>(a) Pancreatic exocrine deficiency</li><li>(b) Atrophy of glands from dehydrated secretions blocking the lumens</li><li>(c) Chronic pancreatitis</li> </ul><li>(6) Type 1 diabetes mellitus (20%)</li><ul> <li>Due to chronic pancreatitis</li> </ul><li>(7) Infertility in males (95%)
<blockquote style="color: blue; ">CF: males infertile > females</blockquote></li><ul> <li>Atresia of vas deferens</li> </ul><li>(8) Infertility in females (20%)</li><li>(9) Meconium ileus (20%)</li><ul> <li>Small bowel obstruction in newborn
<blockquote style="color: blue; ">CF: meconium ileus; rectal prolapse</blockquote></li> </ul><li>(10) Rectal prolapse</li><ul> <li>Straining at stool</li> </ul><li>(11) Gallstones (>50%)</li><ul> <li>(a) Usually in older CF patients</li><li>(b) Stasis of thickened bile</li><li>(c) Common bile duct obstruction (15-20%)</li> </ul><li>(12) Secondary biliary cirrhosis</li><ul> <li>Due to obstruction of bile ductules by thick secretions</li> </ul> </ul><li>Screen infants</li><ul> <li>Increased serum immunoreactive trypsin levels
<blockquote style="color: blue; ">CF: serum immunoreactive trypsin excellent screen at birth</blockquote></li> </ul><li>Sweat test findings diagnostic for CF</li><ul> <li>(1) Sweat chloride > 60 mmol/L in children
<blockquote style="color: blue; ">Sweat test: diagnostic test for CF</blockquote></li><li>(2) Sweat chloride > 80 mmol/L in adult</li> </ul><li>Treatment</li><ul> <li>(1) Antibiotics for documented respiratory infections</li><li>(2) Bronchodilators</li><li>(3) Pancreatic enzyme replacement</li><li>(4) Corticosteroids in children (alternate day)</li><li>(5) Vitamin supplements</li><ul> <li>Fat-soluble vitamins important</li> </ul><li>(6) Recombinant human deoxyribonuclease aerosol</li><ul> <li>Improves mucociliary clearance of viscid sputum</li> </ul> </ul> </ol> </ol>
</div></html>
![[16.IX.A.Emphysema]]
<<tiddler [[16.IX.A.Emphysema]]>>
![[16.IX.B.Chronic bronchitis]]
<<tiddler [[16.IX.B.Chronic bronchitis]]>>
![[16.IX.C.Asthma]]
<<tiddler [[16.IX.C.Asthma]]>>
![[16.IX.D.Bronchiectasis]]
<<tiddler [[16.IX.D.Bronchiectasis]]>>
<html><a name="HC016018"></a><span macro="tag [[10 Heart Disorders]] [[10]]"></span> <br><span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapters 4]]"></span> <br> <br><a name="P016022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Edema due to alterations in Starling pressure (transudate)</li><ol type="a"> <li>Increased hydrostatic pressure in pulmonary capillaries</li><ul> <li>Left-sided heart failure, volume overload, mitral stenosis
<blockquote style="color: blue; ">Left-sided heart failure: most common cause of pulmonary edema</blockquote></li> </ul><li>Decreased oncotic pressure</li><ul> <li>Nephrotic syndrome, cirrhosis</li> </ul> </ol><li>Edema due to microvascular or alveolar injury (exudate)</li><ol type="a"> <li>Infections</li><ul> <li>Examples-sepsis, pneumonia</li> </ul><li>Aspiration</li><ul> <li>Examples-drowning (refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>), gastric contents</li> </ul><li>Drugs</li><ul> <li>Example-heroin (refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>)</li> </ul><li>High altitude (refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>)</li><li>Acute respiratory distress syndrome (ARDS; see later)</li> </ol> </ol>
</div></html>
![[16.V.A.Pulmonary edema (refer to Chapters 4 and 10)]]
<<tiddler [[16.V.A.Pulmonary edema (refer to Chapters 4 and 10)]]>>
![[16.V.B.Acute respiratory distress syndrome (ARDS)]]
<<tiddler [[16.V.B.Acute respiratory distress syndrome (ARDS)]]>>
<html><a name="HC016019"></a> <br><a name="P016023"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">ARDS: noncardiogenic pulmonary edema</blockquote>
<ul> <li>Noncardiogenic pulmonary edema resulting from acute alveolar-capillary damage</li><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Due to direct injury to the lungs or systemic diseases</li><li>Risk factors for ARDS
<blockquote style="color: blue; ">RDS risk: sepsis, gastric aspiration, severe trauma</blockquote></li><ul> <li>(1) Gram-negative sepsis (>40% of cases)</li><li>(2) Gastric aspiration (>30% of cases)</li><li>(3) Severe trauma with shock (>20% of cases)</li><li>(4) Diffuse pulmonary infections</li><ul> <li>Severe acute respiratory syndrome (SARS), hantavirus</li> </ul><li>(5) Heroin</li><li>(6) Smoke inhalation</li><li>(7) Acute pancreatitis</li><li>(8) Cardiopulmonary bypass</li><li>(9) Disseminated intravascular coagulation</li><li>(10) Amniotic fluid embolism, fat embolism</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Acute damage to alveolar capillary walls and epithelial cells
<blockquote style="color: blue; ">ARDS: acute alveolar-capillary damage; sepsis most common cause</blockquote></li><li>Alveolar macrophages and other cells release cytokines.</li><ul> <li>(1) Cytokines are chemotactic to neutrophils.
<blockquote style="color: blue; ">Alveolar macrophages: cytokines chemotactic to neutrophils</blockquote></li><li>(2) Neutrophils transmigrate into the alveoli through pulmonary capillaries.</li><li>(3) Capillary damage causes leakage of a protein-rich exudate producing hyaline membranes.</li><li>(4) Neutrophils damage type I and II pneumocytes.</li><ul> <li>Decrease in surfactant causes atelectasis with intrapulmonary shunting.
<blockquote style="color: blue; ">ARDS: neutrophil damage to type I and II pneumocytes</blockquote></li> </ul> </ul><li>Late findings</li><ul> <li>(1) Repair by type II pneumocytes</li><li>(2) Progressive interstitial fibrosis (restrictive lung disease)</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Dyspnea/tachypnea</li><li>Late inspiratory crackles</li> </ol><li>Laboratory findings</li><ol type="a"> <li>Severe hypoxemia <i>not</i> responsive to O<sub>2</sub> therapy
<blockquote style="color: blue; ">ARDS: severe hypoxemia, PA wedge pressure < 18 mm Hg, ↑ <span style="font-variant:small-caps;">a</span>-a gradient</blockquote></li><ul> <li>Pa<span style="font-variant:small-caps;">o</span><sub>2</sub> < 50 mm Hg</li> </ul><li>Pulmonary artery wedge pressure < 18 mm Hg</li><ul> <li>Important in distinguishing ARDS from cardiogenic pulmonary edema</li> </ul><li>Respiratory alkalosis or normal Pa<span style="font-variant:small-caps;">co</span><sub>2</sub></li><li>Increased <span style="font-variant:small-caps;">a</span>-a gradient, due to:</li><ul> <li>(1) Intrapulmonary shunting</li><ul> <li>Related to atelectasis</li> </ul><li>(2) Diffusion abnormalities</li><ul> <li>Related to hyaline membranes, alveolar infiltrate</li> </ul> </ul><li>Chest x-ray</li><ul> <li>(1) Bilateral interstitial infiltrates initially</li><li>(2) Progresses to widespread alveolar consolidation with air bronchograms (80%)</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Treat underlying disease</li><li>Hemodynamic monitoring</li><li>Mechanical ventilation</li><li>Nitric oxide inhalation</li><li>Corticosteroids</li> </ol><li>Poor prognosis (40-50% mortality rate)</li> </ol> </ul>
</div></html>
<html><a name="HC016021"></a> <br><a name="P016024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Classified as community-acquired or nosocomial (hospital-acquired)</li><li>Community-acquired pneumonia is further subdivided into typical and atypical.</li> </ol><li>Typical community-acquired pneumonia</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Majority are caused by bacterial pathogens.</li><li>(2) Most often due to <i>Streptococcus pneumoniae</i> (50-75%; <span>[[Fig. 16-9A|Figure 16-9]]</span>)
<blockquote style="color: blue; "><i>Streptococcus pneumoniae:</i> most common cause of typical community-acquired pneumonia</blockquote></li> </ul><li>Pathogenesis</li><ul> <li>(1) Inhalation of aerosol from an infected patient</li><li>(2) Aspiration of nasopharyngeal flora while sleeping</li> </ul><li>Bronchopneumonia</li><ul> <li>(1) Begins as an acute bronchitis and spreads locally into the lungs</li><li>(2) Usually involves the lower lobes or right middle lobe</li><li>(3) Lung has patchy areas of consolidation (<span>[[Fig. 16-9B|Figure 16-9]]</span>).
<blockquote style="color: blue; ">Bronchopneumonia: acute bronchitis lung parenchyma</blockquote></li><ul> <li>Microabscesses are present in the areas of consolidation.</li> </ul> </ul><li>Lobar pneumonia</li><ul> <li>Complete or almost complete consolidation of a lobe of lung (<span>[[Fig. 16-9C|Figure 16-9]]</span>)</li> </ul><li>Complications</li><ul> <li>(1) Lung abscesses, empyema (pus in the pleural cavity)</li><li>(2) Sepsis</li> </ul><li>Clinical findings</li><ul> <li>(1) Sudden onset of high fever with productive cough</li><li>(2) Chest pain</li><li>(3) Tachycardia</li><li>(4) Signs of consolidation (alveolar exudate)
<blockquote style="color: blue; ">Typical pneumonia: signs of consolidation (alveolar exudate)</blockquote></li><ul> <li>(a) Dullness to percussion</li><li>(b) Increased vocal tactile fremitus</li><ul> <li>Sound is transmitted well through alveolar consolidations.</li> </ul><li>(c) Late inspiratory crackles</li><li>(d) Bronchial breath sounds</li><li>(e) Bronchophony and egophony</li> </ul><li>(5) Chest radiograph (gold standard screen)
<blockquote style="color: blue; ">Chest radiograph: gold standard for diagnosing pneumonia</blockquote></li><ul> <li>(a) Patchy infiltrates (bronchopneumonia) or lobar consolidation (<span>[[Fig. 16-9D|Figure 16-9]]</span>)</li><li>(b) Sensitivity 50% to 85%</li> </ul><li>(6) Laboratory findings</li><ul> <li>(a) Positive Gram stain
<blockquote style="color: blue; ">Positive Gram stain: more useful than culture</blockquote></li><ol type="1"> <li>More useful than culture</li><ul> <li>Cultures are still obtained.</li> </ul><li>Sensitivity 80%</li> </ol><li>(b) Neutrophilic leukocytosis</li><li>(c) Blood cultures positive in 20% of cases.</li> </ul> </ul> </ol><li><span>[[Table 16-4|Table 16-4. SUMMARY OF RESPIRATORY MICROBIAL PATHOGENS]]</span> (<span>[[Fig.16-10A to I|Figure 16-10]]</span>) summarizes important respiratory microbial pathogens.</li><li>Atypical community-acquired pneumonia</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Usually caused by <i>Mycoplasma pneumoniae</i>
<blockquote style="color: blue; "><i>Mycoplasma pneumoniae:</i> most common cause of atypical pneumonia</blockquote></li><li>(2) Other pathogens</li><ul> <li>(a) <i>Chlamydophilia pneumoniae</i></li><li>(b) Viruses</li><ul> <li>Respiratory syncytial virus, influenzavirus, adenovirus</li> </ul><li>(c) <i>Chlamydia trachomatis</i> in newborns</li> </ul> </ul><li>Pathogenesis</li><ul> <li>Contracted by inhalation (droplet infection)</li> </ul><li>Patchy interstitial pneumonia
<blockquote style="color: blue; ">Atypical pneumonia: interstitial pneumonia; no signs of consolidation</blockquote></li><ul> <li>(1) Mononuclear infiltrate</li><li>(2) Alveolar spaces usually free of exudate</li> </ul><li>Clinical findings</li><ul> <li>(1) Insidious onset, low-grade fever</li><li>(2) Nonproductive cough</li><li>(3) Chest pain</li><li>(4) Flu-like symptoms</li><ul> <li>Pharyngitis, laryngitis, myalgias, headache</li> </ul><li>(5) <i>No</i> signs of consolidation</li> </ul> </ol><li>Nosocomial pneumonia</li><ol type="a"> <li>Epidemiology; risk factors:</li><ul> <li>(1) Severe underlying disease</li><li>(2) Antibiotic therapy</li><li>(3) Immunosuppression</li><li>(4) Respirators</li><ul> <li>Most common source of infection</li> </ul> </ul><li>Pathogens</li><ul> <li>(1) Gram-negative bacteria</li><ul> <li><i>Pseudomonas aeruginosa</i> (respirators), <i>Escherichia coli</i>
<blockquote style="color: blue; "><i>Pseudomonas aeruginosa:</i> nosocomial pneumonia; contracted from respirators</blockquote></li> </ul><li>(2) Gram-positive bacteria (e.g., <i>Staphylococcus aureus</i>)</li> </ul> </ol><li>Pneumonia in immunocompromised hosts</li><ol type="a"> <li>Complication of AIDS and bone marrow transplantation</li><li>Common opportunistic infections:</li><ul> <li>(1) Cytomegalovirus (<span>[[Fig. 16-10B|Figure 16-10]]</span>)</li><li>(2) <i>Pneumocystis jiroveci</i> (see Fig. 3-8)
<blockquote style="color: blue; "><i>Pneumocystis jiroveci:</i> most common pathogen causing pneumonia in AIDS</blockquote></li><ul> <li>Trimethoprim-sulfamethoxazole is used for prophylaxis and treatment.</li> </ul><li>(3) <i>Aspergillus fumigatus</i> (<span>[[Fig. 16-10E|Figure 16-10]]</span>)</li> </ul> </ol><li>Tuberculosis (TB)</li><ol type="a"> <li>Epidemiology and pathogenesis</li><ul> <li>(1) Contracted by inhalation of <i>Mycobacterium tuberculosis</i></li><li>(2) Organism resides in phagosomes of alveolar macrophages</li><ul> <li>Produces a protein that prevents fusion of lysosomes with phagosome</li> </ul><li>(3) Characteristics</li><ul> <li>(a) Strict aerobe, acid-fast (due to mycolic acid in cell wall)
<blockquote style="color: blue; ">TB: acid-fastness due to mycolic acid</blockquote></li><li>(b) Cord factor is virulence factor</li> </ul><li>(4) Screening
<blockquote style="color: blue; ">TB: cord factor is virulence factor</blockquote></li><ul> <li>(a) Purified protein derivative (PPD) intradermal skin test</li><li>(b) Does <i>not</i> distinguish active from inactive disease</li> </ul><li>(5) Protein in cell wall</li><ul> <li>Responsible for positive PPD</li> </ul><li>(6) Drug resistance</li><ul> <li>(a) Chromosome mutations involving mycolic acid</li><li>(b) Chromosome mutations involving catalase peroxidase</li><ul> <li>Enzyme is required to activate isoniazid
<blockquote style="color: blue; ">PPD: does <i>not</i> distinguish active from inactive TB</blockquote></li> </ul> </ul> </ul><li>Primary TB</li><ul> <li>(1) Subpleural location (<span>[[Fig. 16-11|Figure 16-11]]</span>)</li><ul> <li>(a) Upper part of the lower lobes or lower part of the upper lobes
<blockquote style="color: blue; ">Primary TB: upper part lower lobes; lower part upper lobes; Ghon complex</blockquote></li><li>(b) Ghon focus (caseous necrosis) in periphery</li><li>(c) Ghon complex (caseous necrosis) in hilar lymph nodes</li> </ul><li>(2) Usually resolves</li><ul> <li>(a) Produces a calcified granuloma or area of scar tissue</li><li>(b) May be a nidus for secondary TB</li> </ul> </ul><li>Secondary (reactivation) TB</li><ul> <li>(1) Due to reactivation of a previous primary TB site</li><li>(2) Involves one or both apices in upper lobes (<span>[[Fig. 16-12|Figure 16-12]]</span>)
<blockquote style="color: blue; ">Reactivation TB: upper lobe cavitary lesion(s)</blockquote></li><ul> <li>Ventilation (oxygenation) is greatest in the upper lobes.</li> </ul><li>(3) Cavitary lesion due to release of cytokines from memory T cells</li> </ul><li>Clinical findings</li><ul> <li>Fever, drenching night sweats, weight loss
<blockquote style="color: blue; ">TB: drenching night sweats, fever, weight loss</blockquote></li> </ul><li>Complications</li><ul> <li>(1) Miliary spread in lungs due to invasion into the bronchus or lymphatics</li><li>(2) Miliary spread to extrapulmonary sites</li><ul> <li>(a) Due to invasion of pulmonary vein tributaries</li><li>(b) Kidney is the most common extrapulmonary site.
<blockquote style="color: blue; ">Kidneys: most common extrapulmonary site in TB</blockquote></li><li>(c) Adrenal involvement may result in Addison's disease.</li> </ul><li>(3) Massive hemoptysis, bronchiectasis, scar carcinoma
<blockquote style="color: blue; ">TB in vertebra: Pott's disease</blockquote></li><li>(4) Granulomatous hepatitis, spread to vertebra (Pott's disease)</li> </ul><li>Diagnosis</li><ul> <li>(1) Bronchoalveolar lavage best for staining and culture</li><li>(2) Sputum cultures</li> </ul><li>Treatment</li><ul> <li>(1) Isoniazid + rifampin + pyrazinamide</li><li>(2) Noninfectious in 2 to 3 weeks</li><li>(3) Treat for additional 9 to 12 months</li><ul> <li>Kills metabolically inactive persisters in lesions</li> </ul> </ul> </ol><li><i>Mycobacterium avium-intracellulare</i> complex (MAC)</li><ol type="a"> <li>Atypical mycobacterium</li><li>Most common TB in AIDS (often disseminates)
<blockquote style="color: blue; ">MAC: most common TB in AIDS</blockquote></li><ul> <li>Occurs when CD4 T<sub>H</sub> count falls below 50 cells/mm<sup>3</sup></li> </ul><li>Treatment</li><ul> <li>Clarithromycin + rifabutin + ethambutol</li> </ul> </ol><li>Systemic fungal infections (see <span>[[Fig. 16-10D to I|Figure 16-10]]</span>)</li><ol type="a"> <li>Contracted from inhalation of the pathogen</li><li>Produce a granulomatous inflammatory reaction with or without caseation</li> </ol> </ol>
</div></html>
<html><a name="HC016022"></a> <br><a name="P016025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes of lung abscesses
<blockquote style="color: blue; ">Lung abscesses: most often due to aspiration of oropharyngeal material</blockquote></li><ol type="a"> <li>Most often due to aspiration of oropharyngeal material (e.g., tonsillar material)</li><ul> <li>(1) Risk factors</li><ul> <li>(a) Alcoholism</li><li>(b) Loss of consciousness</li><li>(c) Recent dental work</li> </ul><li>(2) Microbial pathogens
<blockquote style="color: blue; ">Lung abscesses: mixed aerobic/anaerobic infection</blockquote></li><ul> <li>(a) Aerobic and anaerobic streptococci</li><li>(b) <i>Staphylococcus species</i></li><li>(c) <i>Prevotella</i></li><li>(d) <i>Fusobacterium</i></li> </ul> </ul><li>Complication of bacterial pneumonia</li><ul> <li>Examples-<i>Staphylococcus aureus</i>, <i>Klebsiella pneumoniae</i></li> </ul><li>Septic embolism</li><ul> <li>Example-infective endocarditis</li> </ul><li>Obstructive lung neoplasia</li><ul> <li>From 10% to 15% of abscesses are behind a bronchus obstructed by cancer.</li> </ul> </ol><li>Gross findings</li><ol type="a"> <li>Vary in size and location (<span>[[Fig. 16-13|Figure 16-13]]</span>)</li><li>Those due to aspiration are primarily located on the right side (<span>[[Box 16-1|BOX 16-1 ASPIRATION SITES IN THE LUNGS]]</span>).</li> </ol><li>Clinical findings</li><ol type="a"> <li>Spiking fever with productive cough (foul-smelling sputum)
<blockquote style="color: blue; ">Lung abscesses: chest x-ray shows cavitation and fluid level</blockquote></li><li>Chest imaging shows cavitation with an air-fluid level (<span>[[Fig. 16-14|Figure 16-14]]</span>).</li> </ol><li>Treatment
<blockquote style="color: blue; ">Superior segment, right lower lobe: most common site for aspiration</blockquote></li><ol type="a"> <li>Clindamycin</li><li>Bronchoscopy if does not resolve</li> </ol> </ol>
</div><a name="B016001"></a><div class="BT">BOX 16-1 ASPIRATION SITES IN THE LUNGS</div><a name="PB016004"></a><div class="BB" style="color: rgb(47, 79, 79); ">Foreign material localizes to different portions of the lung, depending on the position of the patient. In the standing or sitting position, material localizes in the posterobasal segment of the right lower lobe; in the supine position, the superior segment of the right lower lobe; and in the right-sided position, the right middle lobe or the posterior segment of the right upper lobe. The most common aspiration site is the superior segment of the right lower lobe.<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-016-g002.jpg" id=""></div></html>
![[16.VI.A.Pneumonia]]
<<tiddler [[16.VI.A.Pneumonia]]>>
![[16.VI.B.Lung abscess]]
<<tiddler [[16.VI.B.Lung abscess]]>>
<html><a name="HC016024"></a> <br><a name="PB016005"></a><div class="BB" style="color: rgb(47, 79, 79); ">In a patient with normal bronchial artery blood flow (originates from thoracic aorta and intercostal arteries) and ventilation, a pulmonary embolus produces a hemorrhagic infarction in ∼10% of cases. However, if the patient has decreased bronchial artery blood flow (e.g., decreased cardiac output), or previously underventilated lung (e.g., obstructive lung disease), then occlusion of the pulmonary vessel will likely result in a hemorrhagic infarction, which significantly increases risk of morbidity and death.
<blockquote style="color: blue; ">Bronchial arteries: arise from aorta and intercostal arteries</blockquote></div><a name="P016032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>Source</li><ul> <li>Majority (95%) originate in the femoral vein
<blockquote style="color: blue; ">Source of pulmonary thromboemboli: femoral veins</blockquote></li> </ul><li>Risk factors for thromboembolism (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li><ul> <li>Stasis of blood flow (e.g., prolonged bed rest), hypercoagulable states</li> </ul><li>Size of the embolus determines pulmonary vessel that is occluded.</li><ul> <li>(1) Large emboli occlude the major vessels (saddle embolus) (<span>[[Fig. 16-15|Figure 16-15]]</span>).</li><li>(2) Small emboli occlude medium-sized and small pulmonary arteries.</li> </ul><li>Potential consequences of pulmonary artery occlusion</li><ul> <li>(1) Increase in pulmonary artery pressure</li><li>(2) Decrease blood flow to pulmonary parenchyma
<blockquote style="color: blue; ">Bronchial arteries: protect lungs from infarction</blockquote></li><ul> <li>May cause hemorrhagic infarction</li> </ul> </ul> </ol><li>Red-blue, raised, wedge-shaped area that extends to the pleural surface (see <span>[[Fig. 1-11C|Figure 1-11]]</span>)</li><ol type="a"> <li>Pleural surface has a fibrinous exudate (produces a pleural friction rub).</li><ul> <li>Hemorrhagic pleural effusion may also occur.</li> </ul><li>Majority are located in the lower lobes.</li><ul> <li>Perfusion is greater than ventilation in the lower lobes.</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Saddle embolus</li><ul> <li>(1) Sudden increase in pulmonary artery pressure
<blockquote style="color: blue; ">Saddle embolus: sudden death</blockquote></li><li>(2) Produces acute right ventricular strain and sudden death</li> </ul><li>Pulmonary infarction</li><ul> <li>(1) Sudden onset of dyspnea and tachypnea</li><li>(2) Fever</li><li>(3) Pleuritic chest pain (pain on inspiration)</li><li>(4) Pleural friction rub</li><li>(5) Pleural effusion</li><li>(6) Expiratory wheezing</li><ul> <li>Due to release of thromboxane A<sub>2</sub> from platelets</li> </ul> </ul> </ol><li>Laboratory findings with a pulmonary infarction
<blockquote style="color: blue; ">Pulmonary infarction: dyspnea and tachypnea most common symptom and sign; respiratory alkalosis; hypoxemia</blockquote></li><ol type="a"> <li>Respiratory alkalosis (arterial P<span style="font-variant:small-caps;">co</span><sub>2</sub> < 33 mm Hg)</li><li>Pa<span style="font-variant:small-caps;">o</span><sub>2</sub> < 80 mm Hg (90% of cases)</li><li>Increase in <span style="font-variant:small-caps;">a</span>-a gradient (100% of cases)</li><li>Increase in <span style="font-variant:small-caps;">d</span>-dimers</li> </ol><li>Diagnosis</li><ol type="a"> <li>Chest x-ray</li><ul> <li>(1) Pleural effusion</li><li>(2) "Cut-off" sign of one or more pulmonary arteries</li><ul> <li>Hypovascularity behind the blocked vessel</li> </ul><li>(3) Hampton's hump</li><ul> <li>Wedge-shaped area of consolidation</li> </ul> </ul><li>Abnormal perfusion radionuclide scan</li><ul> <li>(1) Ventilation scan is normal, but the perfusion scan is abnormal (<span>[[Fig. 16-16|Figure 16-16]]</span>).</li><li>(2) Pulmonary angiogram is gold standard confirmatory test.</li><ul> <li>Expensive and not clinically available in smaller hospitals</li> </ul><li>(3) Spiral (helical) CT is excellent if preexisting lung disease is present.</li> </ul><li>Positive <span style="font-variant:small-caps;">d</span>-dimers (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>)
<blockquote style="color: blue; ">Diagnosis: V/Q scan + <span style="font-variant:small-caps;">d</span>-dimers: spira CT</blockquote></li><ul> <li>Usually performed in conjunction with ventilation/perfusion (V/Q) scan or spiral CT</li> </ul> </ol><li>Treatment</li><ul> <li>Refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span></li> </ul><li>Prognosis</li><ol type="a"> <li>∼80% overall survival</li><li>∼60% resolve without treatment</li><li>∼90% resolve with treatment</li> </ol> </ol>
</div></html>
<html><a name="HC016025"></a> <br><a name="P016033"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Pulmonary infarction: normal ventilation scan, abnormal perfusion scan; ↑ <span style="font-variant:small-caps;">d</span>-dimers</blockquote>
<ol type="1"> <li>Definition</li><ol type="a"> <li>Mean pulmonary artery pressure > 25 mm Hg at rest</li><li>Mean pulmonary artery pressure > 30 mm Hg with exercise</li> </ol><li>Epidemiology and pathogenesis</li><ol type="a"> <li>Primary PH</li><ul> <li>(1) Primary type is more common in women.</li><li>(2) Genetic predisposition</li><ul> <li>Mutations in genes associated with transforming growth factor-β</li> </ul><li>(3) Vascular hyperreactivity with proliferation of smooth muscle</li> </ul><li>Secondary PH</li><ul> <li>(1) Endothelial cell dysfunction</li><ul> <li>(a) Loss of vasodilators (e.g., nitric oxide)</li><li>(b) Increase in vasoconstrictors (e.g., endothelin)</li> </ul><li>(2) Hypoxemia and respiratory acidosis stimulate vasoconstriction of pulmonary arteries.
<blockquote style="color: blue; ">Main cause of secondary PH: respiratory acidosis and hypoxemia</blockquote></li><ul> <li>Causes smooth muscle hyperplasia and hypertrophy</li> </ul><li>(3) Causes</li><ul> <li>(a) Chronic hypoxemia</li><ul> <li>Examples-chronic lung disease; living at high altitude</li> </ul><li>(b) Chronic respiratory acidosis</li><ul> <li>Chronic bronchitis (CB); obstructive sleep apnea</li> </ul><li>(c) Loss of pulmonary vasculature</li><ul> <li>Increases workload for remaining vessels; emphysema, recurrent pulmonary emboli</li> </ul><li>(d) Left-to-right cardiac shunts (refer to <span macro="tag [[10 Heart Disorders]] [[Chapter 10]]"></span>)</li><ul> <li>Volume overloading pulmonary vasculature</li> </ul><li>(e) Mitral stenosis</li><ul> <li>Backup of blood into pulmonary veins; pulmonary venous hypertension</li> </ul> </ul> </ul> </ol><li>Pathologic findings</li><ol type="a"> <li>Atherosclerosis of main elastic pulmonary arteries (PAs)
<blockquote style="color: blue; ">PH: atherosclerosis of main PAs</blockquote></li><ul> <li>Due to increased pressure on the endothelium leading to injury</li> </ul><li>Proliferation of myointimal cells and smooth muscle cells</li> </ol><li>Clinical findings</li><ol type="a"> <li>Exertional dyspnea most common presenting sign
<blockquote style="color: blue; ">PH: exertional dyspnea most common symptom</blockquote></li><li>Chest pain</li><li>Chest radiograph shows tapering of the pulmonary arteries
<blockquote style="color: blue; ">PH: tapering of pulmonary arteries on chest x-ray</blockquote></li><li>Accentuated P<sub>2</sub> (sign of PH)</li><li>Left parasternal heave (sign of right ventricular hypertrophy [RVH])</li><ul> <li>PH imposes an increased afterload on the right ventricle.</li> </ul><li>Right-sided heart failure due to cor pulmonale</li> </ol><li>Diagnosis</li><ol type="a"> <li>Catheterization to measure pressures</li><ul> <li>Can also use transthoracic Doppler echocardiogram</li> </ul><li>Chest x-ray</li><ul> <li>(1) Enlargement of main pulmonary arteries</li><ul> <li>Rapid tapering of distal vessels</li> </ul><li>(2) Right ventricular enlargement</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Diuretics</li><li>Oxygen</li><li>Vasodilators</li><ul> <li>Calcium channel blockers, prostanoids, endothelin receptor antagonists</li> </ul><li>Lung transplant</li> </ol><li>Cor pulmonale (<span>[[Fig. 16-17|Figure 16-17]]</span>)
<blockquote style="color: blue; ">Cor pulmonale: PH + RVH</blockquote></li><ul> <li>Combination of PH and right RVH leading to right-sided heart failure</li> </ul> </ol>
</div></html>
<html><a name="HC016026"></a><span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span> <br> <br><a name="P016034"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Goodpasture syndrome: hemoptysis followed by renal failure</blockquote>
<ul> <li>Pulmonary hemorrhage with hemoptysis often precedes renal failure.</li> </ul>
</div></html>
![[16.VII.A.Pulmonary thromboembolism]]
<<tiddler [[16.VII.A.Pulmonary thromboembolism]]>>
![[16.VII.B.Pulmonary hypertension (PH)]]
<<tiddler [[16.VII.B.Pulmonary hypertension (PH)]]>>
![[16.VII.C.Goodpasture syndrome (refer to Chapter 19)]]
<<tiddler [[16.VII.C.Goodpasture syndrome (refer to Chapter 19)]]>>
<html><a name="HC016028"></a> <br><a name="P016038"></a><div class="PA" style="color: black; "><ol type="1"> <li>Chest wall disorders in the presence of normal lungs</li><ul> <li>Examples-kyphoscoliosis, pleural disease (e.g., mesothelioma), obesity</li> </ul><li>Acute or chronic interstitial lung diseases</li><ol type="a"> <li>Acute interstitial disease (e.g., ARDS, see section V)</li><li>Chronic interstitial disease</li><ul> <li>(1) Fibrosing disorders (e.g., pneumoconiosis)</li><li>(2) Granulomatous disease (e.g., sarcoidosis)</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC016029"></a> <br><a name="P016039"></a><div class="PA" style="color: black; "><ol type="1"> <li>Earliest manifestation is an alveolitis.
<blockquote style="color: blue; ">Alveolitis → interstitial fibrosis</blockquote></li><ul> <li>Leukocytes release cytokines, which stimulate fibrosis.</li> </ul><li>Effects of interstitial fibrosis
<blockquote style="color: blue; ">Restrictive lung disease: ↓ compliance, ↑ elasticity</blockquote></li><ol type="a"> <li>Decreases lung compliance</li><ul> <li>(1) Decreased expansion of the lung parenchyma during inspiration</li><li>(2) Damage to type I/II alveolar cells and endothelial cells</li><ul> <li>Functional loss of alveolar and capillary units</li> </ul> </ul><li>Increases lung elasticity</li><ul> <li>Recoil of the lung on expiration is increased.</li> </ul> </ol><li>Clinical and laboratory findings in all restrictive lung diseases</li><ol type="a"> <li>Dry cough and exertional dyspnea</li><li>Late inspiratory crackles in lower lung fields</li><li>Potential for cor pulmonale</li><li>Pulmonary function test findings and arterial blood gases</li><ul> <li>(1) All volumes and capacities are equally decreased.</li><li>(2) Decreased FEV<sub>1 sec</sub> (see <span>[[Fig. 16-1B|Figure 16-1]]</span>)
<blockquote style="color: blue; ">Restrictive lung disease: ↓ volumes/capacities, normal to ↑ FEV<sub>1 sec</sub>/FVC ratio</blockquote></li><ul> <li>Example-3 L (normal 4 L)</li> </ul><li>(3) Decreased FVC (see <span>[[Fig. 16-1B|Figure 16-1]]</span>)</li><ul> <li>Often the same value as FEV<sub>1 sec</sub> (3 L) due to increased lung elasticity</li> </ul><li>(4) Increased ratio of FEV<sub>1 sec</sub>/FVC</li><ul> <li>Example-3/3 = 100% (normal is 80%)</li> </ul><li>(5) Respiratory alkalosis (arterial P<span style="font-variant:small-caps;">co</span><sub>2</sub> < 33 mm Hg)</li><li>(6) Decreased Pa<span style="font-variant:small-caps;">o</span><sub>2</sub></li> </ul><li>Chest radiograph findings</li><ul> <li>Diffuse bilateral reticulonodular infiltrates</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC016030"></a> <br><a name="P016040"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Inhalation of mineral dust into the lungs leading to interstitial fibrosis
<blockquote style="color: blue; ">Pneumoconiosis: inhalation of mineral dust</blockquote></li><ul> <li>(1) Mineral dust includes coal dust, silica, asbestos, and beryllium.</li><li>(2) Accounts for ∼25% of cases of chronic interstitial lung disease</li> </ul><li>Particle size determines site of lung deposition
<blockquote style="color: blue; ">Particle size 1-5 μm: bifurcation respiratory bronchioles and alveolar ducts</blockquote></li><ul> <li>(1) 1- to 5-μm particles</li><ul> <li>Reach the bifurcation of the respiratory bronchioles and alveolar ducts</li> </ul><li>(2) Smaller than 0.5-μm particles
<blockquote style="color: blue; "><0.5 μm: alveoli</blockquote></li><ul> <li>Reach the alveoli and are phagocytosed by alveolar macrophages</li> </ul> </ul><li>Coal dust is the <i>least</i> fibrogenic particle.</li><li>Silica, asbestos, and beryllium are very fibrogenic.</li> </ol><li>Coal worker's pneumoconiosis (CWP)</li><ol type="a"> <li>Sources of coal dust (anthracotic pigment)</li><ul> <li>Coal mines, large urban centers, tobacco smoke</li> </ul><li>Pulmonary anthracosis
<blockquote style="color: blue; ">CWP: anthracotic pigment; also element of obstructive lung disease</blockquote></li><ul> <li>(1) Usually asymptomatic</li><li>(2) Anthracotic pigment in interstitial tissue and hilar nodes</li><ul> <li>Alveolar macrophages with anthracotic pigment are called "dust cells."
<blockquote style="color: blue; ">Dust cells: alveolar macrophages with anthracotic pigment</blockquote></li> </ul> </ul><li>Simple CWP</li><ul> <li>(1) Fibrotic opacities are smaller than 1 cm in upper lobes and upper portions of lower lobes.</li><li>(2) Coal deposits adjacent to respiratory bronchioles produce centriacinar (centrilobular) emphysema (see section IX).</li> </ul><li>Complicated CWP (progressive massive fibrosis)
<blockquote style="color: blue; ">Complicated CWP: black lung disease</blockquote></li><ul> <li>(1) Fibrotic opacities larger than 1 to 2 cm with or without necrotic centers (<span>[[Fig. 16-18|Figure 16-18]]</span>)</li><li>(2) Crippling lung disease ("black lung" disease)
<blockquote style="color: blue; ">CWP: no risk for lung cancer or TB</blockquote></li><li>(3) <i>No</i> increased incidence of TB or primary lung cancer</li><li>(4) Cor pulmonale may occur.
<blockquote style="color: blue; ">Caplan syndrome: pneumoconiosis and cavitating rheumatoid nodules</blockquote></li><li>(5) Caplan syndrome may occur.</li><ul> <li>CWP plus large cavitating rheumatoid nodules in the lungs</li> </ul> </ul> </ol><li>Silicosis</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Most common occupational disease in the world
<blockquote style="color: blue; ">Silicosis: most common occupational disease</blockquote></li><li>(2) Quartz (crystalline silicone dioxide) is most often implicated.</li><ul> <li>Sources: foundries (casting metal), sandblasting, working in mines</li> </ul> </ul><li>Pathogenesis</li><ul> <li>(1) Quartz is highly fibrogenic and deposits in the upper lungs.
<blockquote style="color: blue; ">Silicosis: opacities contain collagen and quartz</blockquote></li><li>(2) Quartz activates and is cytolytic to alveolar macrophages.</li><ul> <li>Macrophages release cytokines that stimulate fibrogenesis.</li> </ul> </ul><li>Acute exposure; chest x-ray findings:</li><ul> <li>Ground glass appearance in all lung fields</li> </ul><li>Chronic exposure; chest x-ray findings:</li><ul> <li>(1) Nodular opacities in the lungs</li><ul> <li>Concentric layers of collagen with or without central cavitation (<span>[[Fig. 16-19|Figure 16-19]]</span>)</li> </ul><li>(2) "Egg-shell" calcification in hilar nodes
<blockquote style="color: blue; ">Silicosis: "egg-shell" calcification in hilar nodes</blockquote></li><ul> <li>Rim of dystrophic calcification in the nodes</li> </ul> </ul><li>Complications</li><ul> <li>(1) Cor pulmonale, Caplan syndrome</li><li>(2) Increased risk for developing lung cancer and TB
<blockquote style="color: blue; ">Silicosis: ↑ risk lung cancer and TB</blockquote></li> </ul> </ol><li>Asbestos-related disease</li><ol type="a"> <li>Geometric forms of asbestos</li><ul> <li>(1) Serpentine</li><ul> <li>(a) Curly and flexible fibers (e.g., chrysotile)</li><li>(b) Produces interstitial fibrosis and lung cancer</li> </ul><li>(2) Amphibole</li><ul> <li>(a) Straight and rigid (e.g., crocidolite)</li><li>(b) Produces interstitial fibrosis, lung cancer, mesothelioma</li> </ul><li>(3) Deposition sites
<blockquote style="color: blue; ">Asbestos fibers deposit in the respiratory unit.</blockquote></li><ul> <li>Respiratory bronchioles, alveolar ducts, alveoli</li> </ul> </ul><li>Sources</li><ul> <li>(1) Insulation around pipes in old naval ships</li><li>(2) Roofing material, ceiling tiles, floor tiles used >20 years ago</li><li>(3) Demolition of old buildings</li> </ul><li>Appearance in tissue</li><ul> <li>(1) Fibers are coated by iron and protein (called ferruginous bodies)
<blockquote style="color: blue; ">Ferruginous bodies: iron-coated asbestos fibers</blockquote></li><ul> <li>Macrophages phagocytose and coat the fibers with ferritin (synthesized by macrophages)</li> </ul><li>(2) Golden, beaded appearance in sputum or in distal, small airways (<span>[[Fig. 16-20|Figure 16-20]]</span>)</li> </ul><li>Asbestos-related disease</li><ul> <li>(1) Benign pleural plaques
<blockquote style="color: blue; ">Benign pleural plaques: most common lesions</blockquote></li><ul> <li>(a) Calcified plaques on the pleura and dome of the diaphragm</li><li>(b) They are <i>not</i> a precursor lesion for a mesothelioma.</li> </ul><li>(2) Diffuse interstitial fibrosis with or without pleural effusions</li><li>(3) Primary bronchogenic carcinoma
<blockquote style="color: blue; ">Bronchogenic carcinoma: most common asbestos-related cancer</blockquote></li><ul> <li>(a) Risk further increases if the patient smokes cigarettes.</li><li>(b) Occurs ∼20 years after first exposure.</li> </ul><li>(4) Malignant mesothelioma of pleura
<blockquote style="color: blue; ">Malignant mesothelioma: arises from serosa of pleura; encases the lung</blockquote></li><ul> <li>(a) <i>No</i> etiologic relationship with smoking</li><li>(b) Arises from the serosal cells lining the pleura</li><li>(c) Encases and locally invades the subpleural lung tissue (<span>[[Fig. 16-21|Figure 16-21]]</span>)</li><li>(d) Occurs ∼25 to 40 years after first exposure</li> </ul><li>(5) <i>No</i> increased risk for TB
<blockquote style="color: blue; ">Asbestos: no risk for TB</blockquote></li> </ul><li>Complications</li><ul> <li>Cor pulmonale, Caplan syndrome
<blockquote style="color: blue; ">Berylliosis: risk for lung cancer</blockquote></li> </ul> </ol><li>Berylliosis</li><ol type="a"> <li>Exposure in the nuclear and aerospace industry</li><li>Diffuse interstitial fibrosis with noncaseating granulomas</li><li>Increased risk for cor pulmonale and primary lung cancer</li> </ol> </ol>
</div></html>
<html><a name="HC016031"></a> <br><a name="P016041"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Sarcoidosis: most common noninfectious granulomatous disease of the lungs</blockquote>
<ul> <li>Multisystem granulomatous disease of unknown etiology</li><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Accounts for ∼25% of cases of chronic interstitial lung disease</li><li>Common in blacks and nonsmokers</li><li>More common in women than men</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Disorder in immune regulation</li><li>CD4 T<sub>H</sub> cells interact with an unknown antigen.
<blockquote style="color: blue; ">Sarcoidosis: CD4 T<sub>H</sub> cells interact with unknown antigen</blockquote></li><ul> <li>Releases cytokines causing formation of noncaseating granulomas</li> </ul><li>Diagnosis of exclusion</li><ul> <li>Must rule out other granulomatous diseases
<blockquote style="color: blue; ">Sarcoidosis: noncaseating granulomas</blockquote></li> </ul> </ol><li>Lung disease</li><ol type="a"> <li>Primary target organ</li><ul> <li>(1) Granulomas located in the interstitium and mediastinal and hilar nodes</li><li>(2) Granulomas contain multinucleated giant cells (<span>[[Fig. 16-22|Figure 16-22]]</span>).</li><ul> <li>Contain laminated calcium concretions (Schaumann bodies) and stellate inclusions (called asteroid bodies)</li> </ul> </ul><li>Dyspnea is the most common symptom.</li> </ol><li>Skin lesions
<blockquote style="color: blue; ">Sarcoidosis: skin nodules have granulomas on biopsy</blockquote></li><ol type="a"> <li>Nodular lesions containing granulomas</li><li>Violaceous rash occurs on the nose and cheeks (called lupus pernio).</li><li>Erythema nodosum</li><ul> <li>(1) Painful nodules on lower extremities</li><li>(2) Inflammation of subcutaneous fat</li> </ul> </ol><li>Eye lesions; produces uveitis:</li><ul> <li>Blurry vision, glaucoma, and corneal opacities</li> </ul><li>Liver lesions</li><ul> <li>Granulomatous hepatitis
<blockquote style="color: blue; ">Sarcoidosis: most common noninfectious granulomatous disease of the liver</blockquote></li> </ul><li>Other multisystem findings</li><ol type="a"> <li>Enlarged salivary and lacrimal glands</li><li>Diabetes insipidus (hypothalamic and posterior pituitary disease)</li><li>Granulomas in the bone marrow and spleen</li> </ol><li>Laboratory findings</li><ol type="a"> <li>Increased angiotensin-converting enzyme (ACE; 60%)
<blockquote style="color: blue; ">Sarcoidosis: ↑ ACE</blockquote></li><ul> <li>Nonspecific finding</li> </ul><li>Hypercalcemia (5% of cases)
<blockquote style="color: blue; ">Sarcoidosis: hypercalcemia due to hypervitaminosis D</blockquote></li><ul> <li>Increased synthesis of 1-α-hydroxylase in granulomas (hypervitaminosis D)</li> </ul><li>Other findings</li><ul> <li>(1) Polyclonal gammopathy</li><li>(2) Cutaneous anergy to common skin antigens (e.g., <i>Candida</i>)</li><ul> <li>Due to consumption of CD4 T<sub>H</sub> cells in granulomas and loss of cells in alveolar secretions
<blockquote style="color: blue; ">Sarcoidosis: diagnosis of exclusion; rule out other granulomatous diseases</blockquote></li> </ul> </ul> </ol><li>Chest radiograph</li><ol type="a"> <li>Enlarged hilar and mediastinal lymph nodes (called "potato nodes")</li><li>Reticulonodular densities throughout the lung parenchyma</li> </ol><li>Treatment</li><ol type="a"> <li>Majority (75-90%) have spontaneous remission in 2 years and do <i>not</i> require treatment.</li><li>Corticosteroids if treatment is required</li><li>Tumor necrosis factor inhibitors</li><li>Hydroxychloroquine useful if skin involvement is present</li> </ol><li>Prognosis</li><ul> <li>Approximately 10% to 15% develop severe interstitial fibrosis, leading to cor pulmonale and death.</li> </ul> </ol> </ul>
</div></html>
<html><a name="HC016032"></a> <br><a name="P016042"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Accounts for ∼15% of cases of chronic interstitial lung disease</li><li>More common in males than in females</li><li>Usually occurs in individuals 40 to 70 years old</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Repeated cycles of alveolitis are triggered by an unknown agent.
<blockquote style="color: blue; ">Idiopathic pulmonary fibrosis: alveolitis leading to interstitial fibrosis; honeycomb lung</blockquote></li><li>Release of cytokines produces interstitial fibrosis.</li><li>Alveolar fibrosis leads to proximal dilation of the small airways.</li><ul> <li>Lung has a honeycomb appearance.</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Fever</li><li>Dyspnea with exertion</li><li>Chronic, nonproductive cough</li><li>Late inspiratory crackles</li> </ol><li>Treatment</li><ul> <li>None very useful</li> </ul><li>Poor prognosis</li> </ol>
</div></html>
<html><a name="HC016033"></a> <br><a name="PB016006"></a><div class="BB" style="color: rgb(47, 79, 79); ">Any unexplained pleural effusion in a young woman is SLE until proved otherwise. Pleural fluid contains an inflammatory infiltrate (exudate), and lupus erythematosus cells (neutrophils with phagocytosed DNA) are sometimes present. One of the key criteria for diagnosing SLE is the presence of serositis, pleuritis with a pleural effusion being an example of this type of inflammation.</div><a name="P016043"></a><div class="PA" style="color: black; "><ol type="1"> <li>Account for ∼10% of cases of chronic interstitial lung disease
<blockquote style="color: blue; ">Collagen vascular diseases with interstitial fibrosis: systemic sclerosis, SLE, RA</blockquote></li><li>Systemic sclerosis (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>)</li><ul> <li>Most common cause of death is lung disease.</li> </ul><li>Systemic lupus erythematosus (SLE)</li><ol type="a"> <li>Interstitial lung disease occurs in 50% of patients.
<blockquote style="color: blue; ">Pleural effusion in young woman: consider SLE</blockquote></li><li>Pleuritis with pleural effusions</li> </ol><li>Rheumatoid arthritis (RA)</li><ol type="a"> <li>Rheumatoid nodules in lungs plus a pneumoconiosis is called Caplan syndrome.</li><li>Pulmonary findings in RA</li><ul> <li>(1) Interstitial fibrosis with or without intrapulmonary rheumatoid nodules</li><ul> <li>Nodules often cavitating</li> </ul><li>(2) Pleuritis with pleural effusions</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC016034"></a> <br><a name="P016044"></a><div class="PA" style="color: black; "><ol type="1"> <li>Extrinsic allergic alveolitis associated with exposure to a <i>known</i> inhaled antigen</li><ul> <li>Does <i>not</i> involve IgE antibodies (type I hypersensitivity) or have eosinophilia</li> </ul><li>Farmer's lung</li><ol type="a"> <li>Exposure to <i>Saccharopolyspora rectivirgula</i> (thermophilic actinomycetes) in moldy hay
<blockquote style="color: blue; ">Farmer's lung: antigen is thermophilic actinomyces in moldy hay</blockquote></li><li>First exposure</li><ul> <li>Patient develops precipitating IgG antibodies (present in serum)</li> </ul><li>Second exposure</li><ul> <li>(1) Antibodies combine with inhaled allergens to form immune complexes.
<blockquote style="color: blue; ">Farmer's lung: type III and IV hypersensitivity</blockquote></li><ul> <li>Type III hypersensitivity reaction</li> </ul><li>(2) Immunocomplexes produce an inflammatory reaction in lung tissue.</li> </ul><li>Chronic exposure</li><ul> <li>Additional component of granulomatous inflammation (type IV hypersensitivity)</li> </ul><li>Treatment</li><ul> <li>(1) Avoidance of antigen with facial mask</li><li>(2) Corticosteroids</li> </ul> </ol><li>Silo filler's disease
<blockquote style="color: blue; ">Silo filler's disease: inhalation of gases (oxides of nitrogen)</blockquote></li><ol type="a"> <li>Inhalation of gases (oxides of nitrogen) from plant material</li><li>Causes an immediate hypersensitivity reaction associated with dyspnea</li><li>Treatment</li><ul> <li>Corticosteroids</li> </ul> </ol><li>Byssinosis</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Occurs in workers in textile factories</li><li>(2) Contact with cotton, linen, hemp products</li><ul> <li>Exposure to bacterial endotoxin from gram-negative bacteria growing on the cotton</li> </ul> </ul><li>Clinical findings
<blockquote style="color: blue; ">Byssinosis: contact with cotton, linen, hemp products; "Monday morning blues"</blockquote></li><ul> <li>(1) Develop dyspnea on exposure to cotton, linen, or hemp products</li><li>(2) Workers feel better over the weekend (no exposure to antigens)</li><ul> <li>Depression occurs when returning to work on Monday ("Monday morning blues")</li> </ul> </ul><li>Treatment</li><ul> <li>Improve dust removal</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC016035"></a> <br><a name="P016045"></a><div class="PA" style="color: black; "><ol type="1"> <li>Amiodarone</li><li>Bleomycin and busulfan</li><li>Cyclophosphamide
<blockquote style="color: blue; ">Drugs: amiodarone, bleomycin, cyclophosphamide, methotrexate</blockquote></li><li>Methotrexate and methysergide</li><li>Nitrosourea and nitrofurantoin</li> </ol>
</div></html>
<html><a name="HC016036"></a> <br><a name="P016046"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acute pneumonitis may occur 1 to 6 months after therapy.</li><li>Clinical findings</li><ol type="a"> <li>Fever</li><li>Dyspnea</li><li>Pleural effusions
<blockquote style="color: blue; ">Radiation: cause of interstitial lung disease</blockquote></li><li>Chest x-ray shows infiltrates</li> </ol><li>Some patients develop chronic radiation pneumonitis.</li> </ol>
</div></html>
![[16.VIII.A.Causes of restrictive disease]]
<<tiddler [[16.VIII.A.Causes of restrictive disease]]>>
![[16.VIII.B.Pathogenesis of interstitial fibrosis]]
<<tiddler [[16.VIII.B.Pathogenesis of interstitial fibrosis]]>>
![[16.VIII.C.Pneumoconioses]]
<<tiddler [[16.VIII.C.Pneumoconioses]]>>
![[16.VIII.D.Sarcoidosis]]
<<tiddler [[16.VIII.D.Sarcoidosis]]>>
![[16.VIII.E.Idiopathic pulmonary fibrosis]]
<<tiddler [[16.VIII.E.Idiopathic pulmonary fibrosis]]>>
![[16.VIII.F.Collagen vascular diseases]]
<<tiddler [[16.VIII.F.Collagen vascular diseases]]>>
![[16.VIII.G.Hypersensitivity pneumonitis]]
<<tiddler [[16.VIII.G.Hypersensitivity pneumonitis]]>>
![[16.VIII.H.Drugs associated with interstitial fibrosis]]
<<tiddler [[16.VIII.H.Drugs associated with interstitial fibrosis]]>>
![[16.VIII.I.Radiation-induced lung disease]]
<<tiddler [[16.VIII.I.Radiation-induced lung disease]]>>
<html><a name="HC016043"></a> <br><a name="P016066"></a><div class="PA" style="color: black; "><ol type="1"> <li>Incidence of lung cancer is declining in men but increasing in women.
<blockquote style="color: blue; ">Primary lung cancer: declining in men, increasing in women</blockquote></li><li>Peak incidence is at 55 to 65 years of age.</li><li>Most common cancer-related death in both men and women</li><li>Causes</li><ol type="a"> <li>Cigarette smoking most common cause
<blockquote style="color: blue; ">Cigarette smoking: most common cause of lung cancer</blockquote></li><ul> <li>Risk increases with quantity and duration of smoking</li> </ul><li>Radon gas (uranium mining)</li><li>Asbestos</li><li>Certain metals</li><ul> <li>Chromium, cadmium, beryllium, arsenic</li> </ul><li>Secondhand smoke</li><li>Ionizing radiation</li><li>Air pollution</li><li>History of tuberculosis</li> </ol><li>Classified as small cell (13%) or non-small cell (87%) cancers</li><ol type="a"> <li>Primary lung cancer by specific type in decreasing incidence</li><ul> <li>(1) Adenocarcinoma</li><li>(2) Squamous cell carcinoma (<span>[[Fig. 16-30A|Figure 16-30]]</span>)</li><li>(3) Small cell lung carcinoma (<span>[[Fig. 16-30B|Figure 16-30]]</span>)</li><li>(4) Large cell carcinoma</li><li>(5) Bronchial carcinoid</li> </ul> </ol><li>Squamous and small cell lung carcinomas
<blockquote style="color: blue; ">Squamous cell and small cell carcinoma: centrally located</blockquote></li><ol type="a"> <li>Greatest smoking association</li><li>Tend to be centrally located (i.e., main stem bronchus) (<span>[[Fig. 16-30C and D|Figure 16-30]]</span>)</li> </ol><li>Adenocarcinomas</li><ol type="a"> <li>Weakest smoking association</li><li>Tend to be more peripherally located (<span>[[Fig. 16-30E and F|Figure 16-30]]</span>)
<blockquote style="color: blue; ">Adenocarcinoma: peripherally located</blockquote></li><ul> <li>Filters in cigarettes remove large carcinogens leaving small ones to move peripherally.</li> </ul> </ol><li>Common sites for metastasis</li><ol type="a"> <li>Hilar lymph nodes most common site</li><li>Adrenal gland (50%)</li><li>Liver (30%)</li><li>Brain (20%)</li><li>Bone (osteolytic)</li> </ol> </ol>
</div></html>
<html><a name="HC016044"></a><span>[[Table 16-6|Table 16-6. TUMORS AND TUMOR-LIKE DISORDERS OF THE LUNG]]</span> <br> <br><a name="PB016009"></a><div class="BB" style="color: rgb(47, 79, 79); ">A <b>solitary pulmonary nodule</b> or coin lesion (e.g., see <span>[[Fig. 16-10G|Figure 16-10]]</span>) is the term applied to a peripheral lung nodule < 5 cm. Causes of a solitary pulmonary nodule in descending order include granulomas (e.g., TB, histoplasmosis), malignancy (usually primary cancer), and a bronchial (chondroid) hamartoma. Patients < 35 years old have a 1% risk of a solitary coin lesion representing a malignancy, but patients ≥ 50 years old have a 50% to 60% risk of malignancy, usually a primary cancer. In evaluating solitary coin lesions, comparing previous chest x-rays for changes in size of the nodule is the most important initial step.
<blockquote style="color: blue; ">Solitary pulmonary nodule: most often granulomas</blockquote></div></html>
<html><a name="HC016045"></a> <br><a name="P016067"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common lung cancer
<blockquote style="color: blue; ">Metastasis: most common lung cancer; breast cancer most common primary cancer</blockquote></li><li>Cancers most often responsible for metastasis</li><ul> <li>(1) Primary breast cancer most common cause</li><li>(2) Colon cancer, renal cell carcinoma</li> </ul> </ol><li>Sites of lung metastasis</li><ol type="a"> <li>Parenchyma (<span>[[Figs. 16-31|Figure 16-31]]</span> and <span>[[16-32|Figure 16-32]]</span>)</li><li>Pleura and pleural space (malignant effusions)</li><li>Lymphatics (causes severe dyspnea)</li> </ol><li>Dyspnea is the most common symptom.</li> </ol>
</div></html>
<html><a name="HC016046"></a> <br><a name="P016068"></a><div class="PA" style="color: black; "><ol type="1"> <li>Cough
<blockquote style="color: blue; ">Cough: most common symptom</blockquote></li><ul> <li>Most common symptom (75%)</li> </ul><li>Weight loss (40%)</li><li>Chest pain (30%)</li><li>Hemoptysis (25-30%)</li><li>Dyspnea</li><li>Pancoast tumor (superior sulcus tumor)</li><ol type="a"> <li>Usually a primary squamous cancer located at the extreme apex of lung</li><li>Destruction of superior cervical sympathetic ganglion produces Horner syndrome (<span>[[Fig.16-33|Figure 16-33]]</span>)
<blockquote style="color: blue; ">Horner syndrome: lid lag, miosis, anhydrosis</blockquote></li><ul> <li>(1) Ipsilateral lid lag</li><li>(2) Miosis (pinpoint pupil)</li><li>(3) Ipsilateral anhydrosis (lack of sweating)</li> </ul> </ol><li>Superior vena cava syndrome (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>; <span>[[Fig. 16-34|Figure 16-34]]</span>)</li><li>Paraneoplastic syndromes</li><ol type="a"> <li>Digital clubbing</li><ul> <li>Due to reactive periosteal changes in the underlying bone</li> </ul><li>Muscle weakness (Eaton-Lambert syndrome)
<blockquote style="color: blue; ">Eaton-Lambert syndrome: muscle weakness; antibody against calcium channel</blockquote></li><ul> <li>(1) Antibody directed against calcium channel in muscle</li><li>(2) Usually associated with small cell carcinoma</li> </ul><li>Ectopic hormone secretion (see earlier)</li> </ol> </ol>
</div></html>
<html><a name="HC016047"></a> <br><a name="P016069"></a><div class="PA" style="color: black; "><ol type="1"> <li>Chest x-ray</li><ol type="a"> <li>Central masses</li><ul> <li>(1) Squamous cell carcinoma</li><li>(2) Small cell carcinoma</li> </ul><li>Peripheral masses</li><ul> <li>(1) Adenocarcinoma</li><li>(2) Scar carcinoma</li> </ul> </ol><li>Sputum cytologic examination</li><li>Fine needle aspiration</li><li>Bronchoscopy with lavage</li><li>New techniques for early detection</li><ol type="a"> <li>Low-dose spiral (helical) CT scan</li><li>Molecular markers in sputum</li> </ol> </ol>
</div></html>
<html><a name="HC016048"></a> <br><a name="P016070"></a><div class="PA" style="color: black; "><ol type="1"> <li>Surgery</li><li>Radiation</li><li>Chemotherapy</li><li>Targeted biologic therapies</li><ul> <li>Bevacizumab and erlotinib</li> </ul> </ol>
</div></html>
<html><a name="HC016049"></a> <br><a name="P016071"></a><div class="PA" style="color: black; "><ol type="1"> <li>Non-small cell cancers fare better than small cell carcinoma.</li><li>Overall combined 5-year survival rate is ∼15%.</li> </ol>
</div></html>
![[16.X.A.Epidemiology]]
<<tiddler [[16.X.A.Epidemiology]]>>
![[16.X.B.Tumors and tumor-like disorders (Table 16-6)]]
<<tiddler [[16.X.B.Tumors and tumor-like disorders (Table 16-6)]]>>
![[16.X.C.Metastatic cancer]]
<<tiddler [[16.X.C.Metastatic cancer]]>>
![[16.X.D.Clinical findings in primary lung cancer]]
<<tiddler [[16.X.D.Clinical findings in primary lung cancer]]>>
![[16.X.E.Diagnosis]]
<<tiddler [[16.X.E.Diagnosis]]>>
![[16.X.F.Treatment]]
<<tiddler [[16.X.F.Treatment]]>>
![[16.X.G.Prognosis]]
<<tiddler [[16.X.G.Prognosis]]>>
<html><a name="HC016051"></a> <br><a name="P016075"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Usually metastatic primary lung cancer in older patients</li><li>Usually primary disease in younger patients</li><li>Anterior mediastinum is the most common site (>50%).
<blockquote style="color: blue; ">Anterior compartment: most common site for mediastinal masses</blockquote></li><li>Most common primary mediastinal masses, in descending order:</li><ul> <li>(1) Neurogenic tumors</li><ul> <li>(a) Located in the posterior mediastinum</li><li>(b) Usually malignant in children</li><ul> <li>Neuroblastoma</li> </ul><li>(c) Usually benign in adults</li><ul> <li>Ganglioneuroma
<blockquote style="color: blue; ">Neurogenic tumors: most common mediastinal mass; located in posterior mediastinum</blockquote></li> </ul> </ul><li>(2) Thymomas (see later)</li><li>(3) Pericardial cyst</li><ul> <li>Located in the middle mediastinum</li> </ul><li>(4) Malignant lymphomas</li><ul> <li>(a) Located in the anterior mediastinum</li><li>(b) Usually nodular sclerosing Hodgkin's lymphoma in a woman</li> </ul><li>(5) Teratoma</li><ul> <li>(a) Located in the anterior mediastinum</li><li>(b) Majority are benign cystic teratomas.</li><li>(c) Small percentage are malignant teratomas.</li> </ul> </ul> </ol><li>Thymoma</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Located in the anterior mediastinum</li><li>(2) Benign (70%), malignant (30%)</li> </ul><li>Epithelium, <i>not</i> lymphoid tissue, is the neoplastic component.</li><li>Majority express systemic symptoms of myasthenia gravis (refer to <span macro="tag [[23 Musculoskeletal and Soft Tissue Disorders]] [[Chapter 23]]"></span>).
<blockquote style="color: blue; ">Symptoms in thymomas: most often associated with myasthenia gravis</blockquote></li><ul> <li>(1) Less than 15% of myasthenia patients have a thymoma.</li><li>(2) Majority (65-75%) have follicular B cell hyperplasia in the thymus.</li><ul> <li>Site for synthesis of antiacetylcholine receptor antibodies</li> </ul> </ul><li>Other thymoma associations</li><ul> <li>(1) Hypogammaglobulinemia</li><li>(2) Pure RBC aplasia</li><li>(3) Increased incidence of autoimmune disease (e.g. Graves' disease)</li> </ul> </ol> </ol>
</div></html>
![[16.XI.A.Mediastinal masses]]
<<tiddler [[16.XI.A.Mediastinal masses]]>>
<html><a name="HC016053"></a> <br><a name="P016078"></a><div class="PA" style="color: black; "><ol type="1"> <li>Fluid moves from parietal pleura to pleural space to lungs.
<blockquote style="color: blue; ">PF movement: parietal pleura to pleural space to lungs</blockquote></li><li>Movement depends upon the balance of Starling pressures (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>).</li><ol type="a"> <li>Parietal capillary hydrostatic pressure > visceral capillary hydrostatic pressure.</li><li>Parietal capillary oncotic pressure equals visceral capillary hydrostatic pressure.</li> </ol> </ol>
</div></html>
<html><a name="HC016054"></a> <br><a name="P016079"></a><div class="PA" style="color: black; "><ol type="1"> <li>Increased hydrostatic pressure in visceral pleura</li><ul> <li>Example-congestive heart failure</li> </ul><li>Decreased oncotic pressure</li><ul> <li>Example-nephrotic syndrome</li> </ul><li>Obstruction of lymphatic drainage from the visceral pleura</li><ul> <li>Example-lung cancer</li> </ul><li>Increased vessel permeability of visceral pleural capillaries</li><ul> <li>Examples-pulmonary infarction, pneumonia</li> </ul><li>Metastasis to the pleura</li><ul> <li>Example-metastatic breast cancer</li> </ul> </ol>
</div></html>
<html><a name="HC016055"></a> <br><a name="P016080"></a><div class="PA" style="color: black; "><ol type="1"> <li>Transudates</li><ol type="a"> <li>Ultrafiltrate of plasma involving disturbances in Starling pressures</li><li>Examples
<blockquote style="color: blue; ">Congestive heart failure: most common overall cause of a pleural effusion</blockquote></li><ul> <li>(1) Increased hydrostatic pressure in congestive heart failure</li><li>(2) Decreased oncotic pressure in nephrotic syndrome</li> </ul> </ol><li>Exudates</li><ol type="a"> <li>Protein-rich and cell-rich fluid
<blockquote style="color: blue; ">PF exudate: acute inflammation; infarction, pneumonia, metastasis</blockquote></li><ul> <li>Due to an increased vessel permeability in acute inflammation</li> </ul><li>Examples-pneumonia, tuberculosis, infarction, metastasis</li> </ol><li>Chylous
<blockquote style="color: blue; ">PF exudate: tuberculosis and malignancy most common cause</blockquote></li><ol type="a"> <li>Indicates interruption of the thoracic duct</li><li>Etiology</li><ul> <li>(1) Malignancy (most common)</li><ul> <li>Blocks lymphatic drainage</li> </ul><li>(2) Trauma</li><ul> <li>Iatrogenic tear during surgery or pathologic
<blockquote style="color: blue; ">Chylous effusion: lymphedema; malignancy most common cause</blockquote></li> </ul> </ul><li>Turbid, milky appearance</li><ul> <li>(1) Due to chylomicrons (diet-derived triglyceride; refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)</li><li>(2) Chylomicrons form a supranate in a test tube after refrigeration.</li> </ul><li>PF triglyceride > 110 mg/dL is diagnostic.</li> </ol><li>Pseudochylous</li><ol type="a"> <li>Turbid, milky appearance</li><li>Caused by inflammation with increased amount of necrotic debris</li><ul> <li>PF cholesterol increased</li> </ul><li>Most commonly caused by rheumatoid lung disease
<blockquote style="color: blue; ">Pseudochylous effusion: pleural effusion in RA</blockquote></li> </ol><li>Laboratory distinction of transudates versus exudates (<span>[[Table 16-7|Table 16-7. PLEURAL FLUID (PF) TRANSUDATES VERSUS EXUDATES]]</span>)</li><ol type="a"> <li>PF and serum concentrations of lactate dehydrogenase (LDH) and protein are most useful.</li><ul> <li>Ratios of PF protein and LDH to serum protein and LDH increase test sensitivity and specificity.</li> </ul><li>Test sensitivity is 99% and specificity is 98% if at least one of the three criteria for an exudate is present.</li><li>Additional criteria</li><ul> <li>(1) pH > 7.4 indicates a transudate.</li><li>(2) pH < 7.4 indicates an exudate.</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Dullness to percussion</li><li>Absent breath sounds</li><li>Absent vocal tactile fremitus</li><li>Contralateral shift of the mediastinum</li><ul> <li>Only large effusions
<blockquote style="color: blue; ">Pleural effusion: blunting costophrenic angle; obscure diaphragm</blockquote></li> </ul> </ol><li>Imaging (<span>[[Fig. 16-35|Figure 16-35]]</span>)</li><ol type="a"> <li>Blunting of the costophrenic angle</li><li>Obscuration of the diaphragm</li> </ol> </ol>
</div></html>
<html><a name="HC016056"></a> <br><a name="P016081"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>More common in men than women
<blockquote style="color: blue; ">Spontaneous pneumothorax: commonly seen in tall, thin, young men</blockquote></li><li>Commonly seen in tall, thin, young men 20 to 40 years of age</li><li>Risk increases with smoking</li><li>Approximately 25% recurrence rate within 2 years</li> </ol><li>Causes</li><ol type="a"> <li>Primary (idiopathic; most common)
<blockquote style="color: blue; ">Spontaneous pneumothorax: rupture of apical subpleural bleb</blockquote></li><ul> <li>(1) Rupture of apical subpleural bleb(s)</li><li>(2) Blebs are secondary to high negative intrapleural pressures.</li><li>(3) Most patients are male smokers between 30 and 40 years old.</li><li>(4) Recurrence in the contralateral lung is common.</li> </ul><li>Chronic obstructive lung disease</li><ul> <li>(1) Most common secondary cause
<blockquote style="color: blue; ">Spontaneous pneumothorax: emphysema most common secondary cause</blockquote></li><li>(2) Paraseptal emphysema</li> </ul><li>Marfan syndrome</li><li>Scuba diving</li><li>Insertion of subclavian catheter</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Rupture of a subpleural or intrapleural bleb produces a hole in the pleura.</li><li>Pleural cavity pressure is the <i>same</i> as the atmospheric pressure.
<blockquote style="color: blue; ">Spontaneous pneumothorax: loss of negative intrathoracic pressure</blockquote></li><ul> <li>(1) Loss of the negative intrathoracic pressure</li><li>(2) Causes a portion of lung or the entire lung to collapse</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Sudden onset of dyspnea with pleuritic type of chest pain (90%)
<blockquote style="color: blue; ">Spontaneous pneumothorax: sudden onset of dyspnea and pleuritic chest pain</blockquote></li><li>Physical examination</li><ul> <li>(1) Tympanitic percussion note</li><li>(2) Absent breath sounds</li><li>(3) Trachea deviated to the side of the collapse if there is total lung collapse</li> </ul> </ol><li>Upright chest x-ray</li><ol type="a"> <li>White visceral pleural line</li><li>Absence of vessel markings peripheral to line</li> </ol><li>Treatment</li><ol type="a"> <li>Observation alone if asymptomatic and pneumothorax < 15%</li><li>One hundred percent oxygen administration</li><ul> <li>Reduces partial pressure of nitrogen; hence, increasing rate of pneumothorax absorption</li> </ul><li>Chest tube insertion or thoracoscopy may be required.</li> </ol> </ol>
</div></html>
<html><a name="HC016057"></a> <br><a name="P016082"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes</li><ol type="a"> <li>Penetrating trauma to the lungs (e.g., knife wound)
<blockquote style="color: blue; ">Tension pneumothorax: penetrating trauma to lungs; check valve type of pleural tear</blockquote></li><li>Rupture of tension pneumatocysts (see section VI)</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Flap-like pleural tear (check valve) allows air into the pleural cavity but prevents its exit.</li><ul> <li>Similar in concept to filling a tire up with air</li> </ul><li>Increased pleural cavity pressure
<blockquote style="color: blue; ">Tension pneumothorax: increase in pleural cavity pressure with each breath</blockquote></li><li>Produces compression atelectasis (see section IV)</li> </ol><li>Clinical findings</li><ol type="a"> <li>Sudden onset of severe dyspnea and pleuritic chest pain</li><li>Physical examination</li><ul> <li>(1) Tympanitic percussion note and absent breath sounds</li><li>(2) Trachea and mediastinal structures deviate to contralateral side if large tension pneumothorax (<span>[[Fig. 16-36|Figure 16-36]]</span>).
<blockquote style="color: blue; ">Tension pneumothorax: trachea deviates to contralateral side</blockquote></li><ul> <li>Compromised venous return to the heart, if the pneumothorax is located on the left side</li> </ul> </ul><li>Treatment</li><ul> <li>(1) Relieve pressure first.</li><ul> <li>Insert a needle into the second intercostal space on the midclavicular line.</li> </ul><li>(2) Insert a chest tube.</li> </ul> </ol> </ol>
</div></html>
![[16.XII.A.Movement of pleural fluid (PF)]]
<<tiddler [[16.XII.A.Movement of pleural fluid (PF)]]>>
![[16.XII.B.Etiology and pathogenesis of pleural effusions]]
<<tiddler [[16.XII.B.Etiology and pathogenesis of pleural effusions]]>>
![[16.XII.C.Types of pleural effusions]]
<<tiddler [[16.XII.C.Types of pleural effusions]]>>
![[16.XII.D.Spontaneous pneumothorax]]
<<tiddler [[16.XII.D.Spontaneous pneumothorax]]>>
![[16.XII.E.Tension pneumothorax]]
<<tiddler [[16.XII.E.Tension pneumothorax]]>>
<html><a name="HC017002"></a> <br><a name="P017001"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common congenital disorder of oral cavity
<blockquote style="color: blue; ">Cleft lip/palate: most common congenital disorder of oral cavity</blockquote></li><ul> <li>∼1:800 live births</li> </ul><li>Genetic factors involved</li><ul> <li>Recurrence in subsequent siblings (3%)</li> </ul><li>More common in whites than blacks</li><li>Cleft lip and palate (50%)</li><li>Cleft lip alone (25%)</li><ul> <li>Male > female</li> </ul><li>Cleft palate alone (25%; <span>[[Fig. 17-1|Figure 17-1]]</span>)</li><ul> <li>Female > male</li> </ul><li>Complications</li><ul> <li>(1) Malocclusion</li><li>(2) Eustachian tube dysfunction</li><ul> <li>Chronic otitis media</li> </ul><li>(3) Speech problems
<blockquote style="color: blue; ">Cleft lip/palate: failure of fusion of facial processes</blockquote></li> </ul> </ol><li>Pathogenesis</li><ul> <li>Failure of fusion of facial processes</li> </ul><li>Treatment is surgery.</li> </ol>
</div></html>
<html><a name="HC017003"></a><span>[[Fig. 17-2|Figure 17-2]]</span> <br><span>[[Table 17-1|Table 17-1. INFECTIONS OF THE ORAL CAVITY]]</span> <br> <br> </html>
<html><a name="HC017004"></a> <br><a name="P017002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Candidiasis (see <span>[[Fig. 17-2F|Figure 17-2]]</span>)</li><ul> <li>Most common oral infection</li> </ul><li>Apthous ulcers (stomatitis; canker sores)</li><ol type="a"> <li>Unknown origin</li><ul> <li>(1) Virus versus immunologic</li><li>(2) Often stress-induced</li> </ul><li>Painful ulcers covered by a shaggy gray membrane (<span>[[Fig. 17-3|Figure 17-3]]</span>)</li> </ol><li>Hairy leukoplakia (see <span>[[Fig. 17-2B|Figure 17-2]]</span>)
<blockquote style="color: blue; ">Pre-AIDS-defining lesions: thrush, hairy leukoplakia, apthous ulcers</blockquote></li><ul> <li>Glossitis due to Epstein-Barr virus (EBV)</li> </ul><li>Kaposi's sarcoma</li><ol type="a"> <li>Hard palate is the most common location.</li><li>Due to human herpesvirus 8
<blockquote style="color: blue; ">Kaposi's sarcoma: hard palate; HHV-8</blockquote></li> </ol> </ol>
</div></html>
<html><a name="HC017005"></a> <br><a name="P017003"></a><div class="PA" style="color: black; "><ol type="1"> <li><i>Streptococcus mutans</i> produces acid from sucrose fermentation.</li><ul> <li>Acid erodes enamel and exposes underlying dentine.
<blockquote style="color: blue; ">Dental caries: caused by <i>Streptococcus mutans</i></blockquote></li> </ul><li>Fluoride prevents dental caries.
<blockquote style="color: blue; ">Fluoride: prevents dental caries</blockquote></li><ul> <li>Excess fluoride causes a chalky discoloration of the teeth.</li> </ul> </ol>
</div></html>
<html><a name="HC017006"></a> <br><a name="P017004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pemphigus vulgaris and mucous membrane pemphigoid</li><ul> <li>Both are immunologic skin disorders (refer to <span macro="tag [[24 Skin Disorders]] [[Chapter 24]]"></span>).</li> </ul><li>Erythema multiforme (refer to <span macro="tag [[24 Skin Disorders]] [[Chapter 24]]"></span>)</li><ol type="a"> <li>Hypersensitivity reaction against <i>Mycoplasma</i> or drugs (e.g., sulfonamides)</li><li>Called Stevens-Johnson syndrome when it involves the mouth</li> </ol><li>Apthous ulcers (stomatitis; see <span>[[Fig. 17-3|Figure 17-3]]</span>)</li><li>Behçet's syndrome
<blockquote style="color: blue; ">Behcet's syndrome: recurrent apthous ulcers, uveitis, genital ulcers</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Combination of environmental + genetic factors</li><ul> <li>HLA-B51, HLA-B27 associations</li> </ul><li>(2) May be precipitated by herpes simplex or parvovirus</li><li>(3) High incidence in Turkey and eastern Mediterranean</li> </ul><li>Pathophysiology</li><ul> <li>Immune complex small vessel vasculitis</li> </ul><li>Clinical findings</li><ul> <li>(1) Recurrent aphthous ulcers, genital ulcerations</li><li>(2) Uveitis, erythema nodosum</li><li>(3) Attacks last 1 to 4 weeks</li> </ul><li>Treatment</li><ul> <li>(1) Anti-inflammatory medications</li><li>(2) Corticosteroids</li><li>(3) Colchicine</li><li>(4) Thalidomide</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017007"></a> <br><a name="P017005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Peutz-Jeghers syndrome (see section IV)</li><ul> <li>Melanin pigmentation of the lips and oral mucosa (<span>[[Fig. 17-4|Figure 17-4]]</span>)</li> </ul><li>Addison's disease (see <span>[[Fig. 22-21|Figure 22-21]]</span>)
<blockquote style="color: blue; ">Melanin pigmentation in oral mucosa: Addison's disease, Peutz-Jeghers syndrome</blockquote></li><ol type="a"> <li>Increased adrenocorticotropic hormone (ACTH) stimulates melanocytes.</li><li>Melanin pigmentation of the buccal mucosa</li> </ol><li>Lead poisoning</li><ul> <li>Lead deposits along the gingival margins in adults with gingivitis</li> </ul> </ol>
</div></html>
<html><a name="HC017008"></a> <br><a name="P017006"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Tooth discoloration: tetracycline, ↑ fluoride, erythropoietic porphyria</blockquote>
<ol type="1"> <li>Tetracycline</li><ol type="a"> <li>Drug discolors newly formed teeth.</li><li>Drug <i>not</i> recommended in a child < 12 years of age.</li> </ol><li>Excess fluoride</li><ul> <li>Mottled, chalky white discoloration</li> </ul><li>Congenital erythropoietic porphyria</li><ol type="a"> <li>Porphyrins deposit in the teeth</li><li>Reddish brown discoloration</li> </ol> </ol>
</div></html>
<html><a name="HC017009"></a> <br><a name="P017007"></a><div class="PA" style="color: black; "><ol type="1"> <li>Myxedema</li><ul> <li>Severe primary hypothyroidism</li> </ul><li>Down syndrome
<blockquote style="color: blue; ">Macroglossia: myxedema, Down syndrome, acromegaly, amyloidosis, MENIIb</blockquote></li><li>Acromegaly</li><li>Amyloidosis</li><li>Mucosal neuromas in multiple endocrine neoplasia (MEN) syndrome IIb (III)</li> </ol>
</div></html>
<html><a name="HC017010"></a> <br><a name="P017008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sore, beefy red tongue with or without papillary atrophy</li><li>Causes
<blockquote style="color: blue; ">Glossitis: deficiency of iron, B<sub>12</sub>, folate, vitamin C, niacin; scarlet fever; hairy leukoplakia</blockquote></li><ol type="a"> <li>Long-standing iron deficiency</li><li>Vitamin B<sub>12</sub> or folate deficiency</li><li>Scurvy (vitamin C deficiency)</li><li>Pellagra (niacin deficiency)</li><li>Scarlet fever</li><li>EBV-associated hairy leukoplakia</li> </ol> </ol>
</div></html>
<html><a name="HC017011"></a> <br><a name="P017009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Leukoplakia literally means "white patch" (<span>[[Fig. 17-5|Figure 17-5]]</span>).</li><ul> <li>It has an ∼30% rate of progression to oral cancer.</li> </ul><li>Erythroplakia is a red patch (<span>[[Fig. 17-6|Figure 17-6]]</span>).</li><ul> <li>It has an ∼60% rate of progression to oral cancer.</li> </ul><li>Lesion does <i>not</i> wipe off.</li><li>Both lesions are due to squamous hyperplasia of the epidermis.</li><ul> <li>Increased risk for squamous dysplasia or invasive squamous cancer</li> </ul><li>Causes</li><ol type="a"> <li>Chronic irritation (e.g., dentures)
<blockquote style="color: blue; ">Leukoplakia/erythroplakia: smoking and alcohol are major risk factors</blockquote></li><li>All forms of tobacco use</li><li>Alcohol abuse</li><li>Human papillomavirus (HPV)</li> </ol><li>Locations</li><ol type="a"> <li>Vermilion border lower lip (most common site)</li><li>Buccal mucosa</li><li>Hard and soft palates
<blockquote style="color: blue; ">Leukoplakia/erythroplakia: biopsy to rule out squamous dysplasia or cancer</blockquote></li><li>Floor of the mouth</li> </ol><li>Always biopsy these lesions because of the high risk for progression to oral cancer.</li> </ol>
</div></html>
<html><a name="HC017012"></a><span macro="tag [[24 Skin Disorders]] [[Chapter 24]]"></span> <br> <br><a name="P017010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Often associated with Wickham's stria on buccal mucosa
<blockquote style="color: blue; ">Wickham's stria: association with squamous dysplasia or cancer</blockquote></li><ul> <li>Fine, white, lacy lesions</li> </ul><li>May be associated with squamous cell carcinoma</li> </ol>
</div></html>
<html><a name="HC017013"></a> <br><a name="P017011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Derives from epithelial elements of dental origin (odontogenic origin)
<blockquote style="color: blue; ">Dentigerous cyst: association with 3rd molar and ameloblastoma</blockquote></li><li>Associated with the crown of an unerupted or impacted third molar tooth</li><li>Association with ameloblastomas in 15% to 30% of cases</li> </ol>
</div></html>
<html><a name="HC017014"></a> <br><a name="P017012"></a><div class="PA" style="color: black; "><ol type="1"> <li>Squamous papillomas
<blockquote style="color: blue; ">Squamous papillomas: most common benign tumor in oral cavity</blockquote></li><ol type="a"> <li>Most common benign tumor in oral cavity</li><li>Exophytic tumor with a fibrovascular core</li><li>May occur on the tongue, gingiva, palate, or lips</li> </ol><li>Ameloblastoma</li><ol type="a"> <li>Arise from enamel organ epithelium or a dentigerous cyst
<blockquote style="color: blue; ">Ameloblastoma: most common odontogenic tumor; "soap bubble" appearance in mandible</blockquote></li><li>Located in the mandible</li><ul> <li>(1) Produces a radiolucency in bone that has a "soap bubble" appearance</li><li>(2) Locally invasive but do <i>not</i> metastasize</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017015"></a> <br><a name="P017013"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Majority are well-differentiated squamous cell carcinomas</li><li>More common in men than women</li><li>Risk factors
<blockquote style="color: blue; ">Squamous cell carcinoma: smoking products most common risk factor</blockquote></li><ul> <li>(1) Smoking is the most common risk factor.</li><ul> <li>Pipe, cigarettes, chewing tobacco</li> </ul><li>(2) Alcohol abuse (synergistic with smoking)</li><li>(3) Synergism between smoking and alcohol excess</li><ul> <li>Increases relative risk 30-fold</li> </ul><li>(4) HPV</li><li>(5) Chronic irritation from dentures</li><li>(6) Lichen planus</li> </ul><li>Cancer sites in descending order
<blockquote style="color: blue; ">Squamous cell carcinoma: most common site is lower lip</blockquote></li><ul> <li>(1) Lower lip (vermilion border; <span>[[Fig. 17-7|Figure 17-7]]</span>)</li><li>(2) Floor of mouth</li><li>(3) Lateral border of tongue</li> </ul><li>Metastasis</li><ul> <li>"Tonsillar node" (superior jugular node)</li> </ul><li>Verrucous carcinoma</li><ul> <li>Associated with smokeless tobacco</li> </ul><li>Basal cell carcinoma</li><ul> <li>(1) Most common cancer of upper lip</li><li>(2) Associated with ultraviolet light B exposure
<blockquote style="color: blue; ">Basal cell carcinoma: most common oral site is upper lip</blockquote></li> </ul> </ol><li>Treatment for squamous cancer</li><ul> <li>Surgery and radiation; chemotherapy in advanced cases</li> </ul> </ol>
</div></html>
<html><a name="HC017016"></a> <br><a name="P017014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sjögren's syndrome (refer to <span macro="tag [[23 Musculoskeletal and Soft Tissue Disorders]] [[Chapter 23]]"></span>)
<blockquote style="color: blue; ">Sjögren's syndrome: dry eyes, dry mouth</blockquote></li><ol type="a"> <li>Female dominant autoimmune disease associated with rheumatoid arthritis</li><li>Autoimmune destruction of minor salivary glands and lacrimal glands</li> </ol><li>Salivary gland tumors</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Parotid gland is the most common site.
<blockquote style="color: blue; ">Parotid gland: most common site for salivary gland tumors</blockquote></li><ul> <li>Major salivary gland tumors are more likely to be benign.</li> </ul><li>(2) Minor salivary gland tumors are more likely to be malignant.</li> </ul><li>Pleomorphic adenoma (mixed tumor)</li><ul> <li>(1) Most common benign tumor of major and minor salivary glands
<blockquote style="color: blue; ">Pleomorphic adenoma: most common salivary gland tumor</blockquote></li><ul> <li>Parotid gland is the most common site.</li> </ul><li>(2) Female dominant</li><li>(3) Painless, moveable mass at the angle of the jaw</li><li>(4) Epithelial cells intermixed with myxomatous and cartilaginous stroma</li><ul> <li>Tumor projections through capsule increase risk of recurrence</li> </ul><li>(5) May transform into a malignant tumor</li><ul> <li>Facial nerve involvement is a sign of malignancy.</li> </ul> </ul><li>Warthin's tumor (papillary cystadenoma lymphomatosum)</li><ul> <li>(1) Benign parotid gland tumor
<blockquote style="color: blue; ">Warthin's tumor: heterotopic salivary gland tissue in a lymph node</blockquote></li><ul> <li>Male dominant</li> </ul><li>(2) Heterotopic salivary gland tissue trapped in a lymph node</li><ul> <li>Cystic glandular structures are located within benign lymphoid tissue.</li> </ul> </ul><li>Mucoepidermoid carcinoma
<blockquote style="color: blue; ">Mucoepidermoid carcinoma: most common malignant salivary gland tumor</blockquote></li><ul> <li>(1) Most common malignant salivary gland tumor</li><li>(2) Most commonly located in the parotid gland</li><li>(3) Mixture of neoplastic squamous and mucus-secreting cells</li> </ul> </ol> </ol>
</div></html>
![[17.I.A.Cleft lip and palate]]
<<tiddler [[17.I.A.Cleft lip and palate]]>>
![[17.I.B.Common infections in the oral cavity (Table 17-1 and Fig. 17-2)]]
<<tiddler [[17.I.B.Common infections in the oral cavity (Table 17-1 and Fig. 17-2)]]>>
![[17.I.C.Oral manifestation of HIV]]
<<tiddler [[17.I.C.Oral manifestation of HIV]]>>
![[17.I.D.Dental caries]]
<<tiddler [[17.I.D.Dental caries]]>>
![[17.I.E.Noninfectious ulcerations in the oral cavity]]
<<tiddler [[17.I.E.Noninfectious ulcerations in the oral cavity]]>>
![[17.I.F.Pigmentation abnormalities]]
<<tiddler [[17.I.F.Pigmentation abnormalities]]>>
![[17.I.G.Tooth discoloration]]
<<tiddler [[17.I.G.Tooth discoloration]]>>
![[17.I.H.Macroglossia (enlarged tongue)]]
<<tiddler [[17.I.H.Macroglossia (enlarged tongue)]]>>
![[17.I.I.Glossitis (inflammation of tongue)]]
<<tiddler [[17.I.I.Glossitis (inflammation of tongue)]]>>
![[17.I.J.Leukoplakia and erythroplakia]]
<<tiddler [[17.I.J.Leukoplakia and erythroplakia]]>>
![[17.I.K.Lichen planus (refer to Chapter 24)]]
<<tiddler [[17.I.K.Lichen planus (refer to Chapter 24)]]>>
![[17.I.L.Dentigerous cyst]]
<<tiddler [[17.I.L.Dentigerous cyst]]>>
![[17.I.M.Benign tumors of the oral cavity (excluding salivary gland)]]
<<tiddler [[17.I.M.Benign tumors of the oral cavity (excluding salivary gland)]]>>
![[17.I.N.Malignant tumors of the oral cavity (excluding salivary gland)]]
<<tiddler [[17.I.N.Malignant tumors of the oral cavity (excluding salivary gland)]]>>
![[17.I.O.Salivary gland disorders]]
<<tiddler [[17.I.O.Salivary gland disorders]]>>
<html><a name="HC017018"></a> <br><a name="P017022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Heartburn</li><ul> <li>Most commonly due to gastroesophageal reflux disease</li> </ul><li>Dysphagia (difficulty swallowing) for solids alone
<blockquote style="color: blue; ">Dysphagia for solids: obstructive lesion</blockquote></li><ol type="a"> <li>Symptom of an obstructive lesion</li><li>Examples-esophageal cancer, esophageal web, stricture</li> </ol><li>Dysphagia for solids and liquids
<blockquote style="color: blue; ">Dysphagia for solids and liquids: motor disorder</blockquote></li><ol type="a"> <li>Symptom of a motility disorder</li><li>Oropharyngeal (upper esophageal) dysphagia</li><ul> <li>(1) Striated muscle dysmotility</li><li>(2) Examples-dermatomyositis, myasthenia gravis, stroke</li> </ul><li>Lower esophageal dysphagia</li><ul> <li>(1) Smooth muscle dysmotility</li><li>(2) Examples-systemic sclerosis, CREST syndrome (see <a title="Go here now" href="/content/bookcontent.cfm?xrefID=P0047#P0047" type="PAGE">page 47</a>), achalasia</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017019"></a> <br><a name="P017023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Characteristics</li><ol type="a"> <li>Proximal esophagus ends blindly (<span>[[Fig. 17-8|Figure 17-8]]</span>).
<blockquote style="color: blue; ">TE fistula: proximal esophagus ends blindly; distal esophagus from trachea</blockquote></li><li>Distal esophagus arises from the trachea.</li> </ol><li>Clinical findings</li><ol type="a"> <li>Maternal polyhydramnios (excess amniotic fluid)</li><ul> <li>Swallowed amniotic fluid cannot be reabsorbed in the small intestine.
<blockquote style="color: blue; ">TE fistula: polyhydramnios</blockquote></li> </ul><li>Abdominal distention in newborn</li><ul> <li>Air in the stomach from tracheal fistula</li> </ul><li>Difficulty with feeding</li><ul> <li>(1) Food regurgitates out of the mouth.</li><li>(2) Chemical pneumonia from aspiration</li> </ul><li>VATER syndrome
<blockquote style="color: blue; ">VATER syndrome: <i>v</i>ertebral abnormalities, <i>a</i>nal atresia, <i>TE</i> fistula, <i>r</i>enal disease, and absent <i>r</i>adius</blockquote></li><ul> <li>(1) <i>V</i>ertebral abnormalities</li><li>(2) <i>A</i>nal atresia</li><li>(3) <i>TE</i> fistula</li><li>(4) <i>R</i>enal disease and absent <i>r</i>adius</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017020"></a><span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span> <br> <br><a name="P017024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Due to chronic iron deficiency
<blockquote style="color: blue; ">Plummer-Vinson syndrome: associated with chronic iron deficiency</blockquote></li><li>Leukoplakia in oral mucosa and esophagus</li><li>Intermittent dysphagia for solids</li><ul> <li>Due to an esophageal web or stricture</li> </ul> </ol>
</div></html>
<html><a name="HC017021"></a> <br><a name="P017025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Types of diverticulum</li><ol type="a"> <li>True diverticulum</li><ul> <li>Outpouching lined by mucosa, submucosa, muscularis propria, and adventitia</li> </ul><li>False, or pulsion diverticulum</li><ul> <li>(1) Weakness in underlying muscle wall</li><li>(2) Outpouching of mucosa and submucosa into area of weakness</li> </ul> </ol><li>Zenker's diverticulum
<blockquote style="color: blue; ">Zenker's diverticulum: most common esophageal diverticulum</blockquote></li><ol type="a"> <li>Pulsion type located in upper esophagus</li><ul> <li>Area of weakness is cricopharyngeus muscle.</li> </ul><li>Clinical findings</li><ul> <li>(1) Painful swallowing</li><li>(2) Halitosis</li><ul> <li>Entrapped food</li> </ul><li>(3) Regurgitate food through mouth</li><li>(4) Diverticulitis</li> </ul><li>Treatment is surgery.</li> </ol> </ol>
</div></html>
<html><a name="HC017022"></a> <br><a name="PB017001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Pleuroperitoneal diaphragmatic hernias</b> (Bochdalek hernia) are present early in life. The visceral contents extend through the posterolateral part of the diaphragm on the left into the chest cavity causing respiratory distress at birth. Loops of bowel are present in the left pleural cavity on radiograph.</div><a name="P017026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Found in 50% of persons over 50 years old</li><ul> <li>Increases with age
<blockquote style="color: blue; ">Hiatal hernia: increases with age</blockquote></li> </ul><li>More common in women than men</li><li>Associations</li><ul> <li>(1) Sigmoid diverticulosis (25%)</li><li>(2) Esophagitis (25%)</li><li>(3) Duodenal ulcers (20%)</li><li>(4) Gallstones (18%)</li> </ul> </ol><li>Sliding hernia</li><ol type="a"> <li>Most common type of hiatal hernia (99%)
<blockquote style="color: blue; ">Hiatal hernia: sliding type most common; proximal stomach in thoracic cavity</blockquote></li><li>Herniation of proximal stomach into thoracic cavity through the diaphragmatic esophageal hiatus</li><li>Clinical findings</li><ul> <li>(1) Heartburn
<blockquote style="color: blue; ">Hiatal hernia: acid reflux most common symptom</blockquote></li><li>(2) Nocturnal epigastric distress from acid reflux</li><li>(3) Hematemesis (vomiting blood)</li><li>(4) Ulceration, stricture</li><li>(5) Bowel sounds heard over left lung base</li> </ul><li>Treatment</li><ul> <li>(1) Nonpharmacologic</li><ul> <li>(a) Reduce intake of foods/drugs that decrease lower esophageal sphincter tone</li><ul> <li>Examples-coffee, chocolate, calcium channel blockers</li> </ul><li>(b) Avoid large quantities of food</li><li>(c) Sleep with head of the bed elevated</li> </ul><li>(2) Pharmacologic</li><ul> <li>(a) H<sub>2</sub> antagonists</li><li>(b) Proton pump inhibitors</li><li>(c) Prokinetic agents</li> </ul><li>(3) Surgery if indicated</li> </ul> </ol><li>Paraesophageal (rolling) hernia (1%)
<blockquote style="color: blue; ">Paraesophageal hernia: gastroesophageal junction at level of diaphragm</blockquote></li><ol type="a"> <li>Gastroesophageal junction remains at the level of the diaphragm.</li><li>Part of the stomach bulges into the thoracic cavity.</li> </ol> </ol>
</div></html>
![[17.II.A.Signs and symptoms of esophageal disease]]
<<tiddler [[17.II.A.Signs and symptoms of esophageal disease]]>>
![[17.II.B.Tracheoesophageal (TE) fistula]]
<<tiddler [[17.II.B.Tracheoesophageal (TE) fistula]]>>
![[17.II.C.Plummer-Vinson syndrome (refer to Chapter 11)]]
<<tiddler [[17.II.C.Plummer-Vinson syndrome (refer to Chapter 11)]]>>
![[17.II.D.Esophageal diverticulum]]
<<tiddler [[17.II.D.Esophageal diverticulum]]>>
![[17.II.E.Hiatal hernia]]
<<tiddler [[17.II.E.Hiatal hernia]]>>
![[17.II.F.Gastroesophageal reflux disease (GERD)]]
<<tiddler [[17.II.F.Gastroesophageal reflux disease (GERD)]]>>
![[17.II.G.Barrett's esophagus]]
<<tiddler [[17.II.G.Barrett's esophagus]]>>
![[17.II.H.Infectious esophagitis]]
<<tiddler [[17.II.H.Infectious esophagitis]]>>
![[17.II.I.Corrosive esophagitis]]
<<tiddler [[17.II.I.Corrosive esophagitis]]>>
![[17.II.J.Esophageal varices]]
<<tiddler [[17.II.J.Esophageal varices]]>>
![[17.II.K.Mallory-Weiss syndrome]]
<<tiddler [[17.II.K.Mallory-Weiss syndrome]]>>
![[17.II.L.Boerhaave's syndrome]]
<<tiddler [[17.II.L.Boerhaave's syndrome]]>>
![[17.II.M.Motor disorders]]
<<tiddler [[17.II.M.Motor disorders]]>>
![[17.II.N.Esophageal tumors]]
<<tiddler [[17.II.N.Esophageal tumors]]>>
<html><a name="HC017023"></a> <br><a name="P017027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Approximately 10% of adults have GERD daily.</li><li>Approximately 80% of pregnant women have GERD.</li><li>Hiatal hernia present in ∼70% of people with GERD.
<blockquote style="color: blue; ">GERD: relaxed LES causes acid reflux</blockquote></li><li>Risk factors</li><ul> <li>(1) Smoking, alcohol</li><li>(2) Caffeine, fatty foods, chocolate</li><li>(3) Pregnancy, obesity</li><li>(4) Hiatal hernia</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Transient relaxation of lower esophageal sphincter (LES)</li><ul> <li>Reflux of acid and bile into the distal esophagus</li> </ul><li>Ineffective esophageal clearance of reflux material</li> </ol><li>Clinical findings</li><ol type="a"> <li>Noncardiac chest pain</li><ul> <li>Heartburn, indigestion</li> </ul><li>Nocturnal cough, nocturnal asthma
<blockquote style="color: blue; ">GERD: nocturnal cough/asthma; acid injury to enamel; Barrett's esophagus</blockquote></li><li>Acid injury to enamel</li><li>Early satiety, abdominal fullness</li><li>Bloating with belching</li><li>Barrett's esophagus</li> </ol><li>Diagnostic tests with atypical presentation
<blockquote style="color: blue; ">GERD atypical presentation: esophageal pH monitoring, endoscopy, manometry</blockquote></li><ol type="a"> <li>Twenty-four-hour esophageal pH monitoring</li><ul> <li>Sensitivity/specificity 80% to 90%</li> </ul><li>Esophageal endoscopy</li><li>Manometry</li><ul> <li>LES pressure < 10 mm Hg</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Nonpharmacologic</li><ul> <li>Similar to hiatal hernia (see earlier)</li> </ul><li>Pharmacologic</li><ul> <li>Similar to hiatal hernia (see earlier)</li> </ul><li>Surgery if indicated</li><ul> <li>(1) Fundoplication procedure</li><li>(2) Involves putting a gastric wrap around the gastroesophageal junction</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017024"></a> <br><a name="P017028"></a><div class="PA" style="color: black; "><ol type="1"> <li>Complication of GERD</li><li>Glandular metaplasia in distal esophagus due to acid injury (see <span>[[Fig. 1-10E|Figure 1-10]]</span>)</li><ul> <li>Gastric-type columnar cells and small intestine-type cells (goblet cells)</li> </ul><li>Complications
<blockquote style="color: blue; ">Barrett's esophagus complications: distal adenocarcinoma, stricture</blockquote></li><ol type="a"> <li>Ulceration with stricture formation (most common)</li><li>Glandular dysplasia with increased risk for distal adenocarcinoma</li> </ol> </ol>
</div></html>
<html><a name="HC017025"></a> <br><a name="P017029"></a><div class="PA" style="color: black; "><ol type="1"> <li>Usually a complication of AIDS
<blockquote style="color: blue; ">AIDS-related esophagitis: HSV, CMV, <i>Candida</i></blockquote></li><li>Pathogens</li><ol type="a"> <li>Herpes simplex virus (HSV)</li><ul> <li>See multinucleated squamous cells with intranuclear inclusions</li> </ul><li>Cytomegalovirus (CMV)</li><ul> <li>See basophilic intranuclear inclusions</li> </ul><li><i>Candida</i></li><ul> <li>See yeasts and pseudohyphae (extended yeast forms)</li> </ul> </ol><li>Presents with painful swallowing (i.e., odynophagia)</li> </ol>
</div></html>
<html><a name="HC017026"></a> <br><a name="P017030"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Corrosive esophagitis: strictures, perforation, squamous cancer</blockquote>
<ol type="1"> <li>Ingestion of strong alkali (e.g., lye) or acid (e.g., HCl)</li><li>Complications</li><ol type="a"> <li>Stricture formation</li><li>Perforation</li><li>Squamous cell carcinoma
<blockquote style="color: blue; ">Left gastric vein drains blood from distal esophagus and proximal stomach into the portal vein.</blockquote></li> </ol> </ol>
</div></html>
<html><a name="HC017027"></a> <br><a name="P017031"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>Dilated submucosal left gastric veins (<span>[[Fig. 17-9|Figure 17-9]]</span>)</li><li>Complication of portal hypertension from cirrhosis</li><ul> <li>Alcohol abuse is the most common cause.
<blockquote style="color: blue; ">Esophageal varices: portal hypertension dilates left gastric veins</blockquote></li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Rupture with massive hematemesis (vomiting blood)
<blockquote style="color: blue; ">Ruptured esophageal varices: most common cause of death in cirrhosis</blockquote></li><li>Most common cause of death in cirrhosis</li> </ol><li>Diagnosis</li><ul> <li>Endoscopy</li> </ul><li>Initial management</li><ol type="a"> <li>Endoscopy
<blockquote style="color: blue; ">Ruptured esophageal varices: endoscopy most important diagnostic procedure</blockquote></li><ul> <li>(1) Most important diagnostic procedure</li><li>(2) Value in treatment of the bleed as well</li> </ul><li>Assess/maintain intravascular volume</li><li>Insert nasogastric tube for gastric aspirate/lavage.</li><ul> <li>(1) Confirms upper gastrointestinal source of bleeding</li><li>(2) Assesses rate of bleeding</li> </ul> </ol><li>Prevention/treatment of bleeds</li><ol type="a"> <li>β-Blockers and isosorbide</li><ul> <li>(1) Decrease rate of recurrent bleeding</li><li>(2) Increase survival by 5% to 10%</li> </ul><li>Transjugular intrahepatic portasystemic stent (TIPS)</li><ul> <li>Used for both treatment of bleeding and intractable ascites</li> </ul><li>Octreotide intravenous drip (somatostatin analogue) for bleeding</li><li>Endoscopic ligation</li><li>Endoscopic sclerotherapy</li><li>Open surgery with stapling</li> </ol> </ol>
</div></html>
<html><a name="HC017028"></a> <br><a name="P017032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Mucosal tear in the proximal stomach and distal esophagus
<blockquote style="color: blue; ">Mallory-Weiss syndrome: mucosal tear of distal esophagus</blockquote></li><ul> <li>Due to severe retching in alcoholics or bulimia</li> </ul><li>Causes hematemesis</li> </ol>
</div></html>
<html><a name="HC017029"></a> <br><a name="P017033"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Boerhaave's syndrome: rupture of distal esophagus</blockquote>
<ol type="1"> <li>Rupture of the distal esophagus</li><li>Causes</li><ol type="a"> <li>Endoscopy (∼75% of cases)</li><li>Retching</li><li>Bulimia</li> </ol><li>Complications</li><ol type="a"> <li>Pneumomediastinum
<blockquote style="color: blue; ">Pneumomediastinum: air in subcutaneous tissue; crunching sound on physical exam</blockquote></li><ul> <li>(1) Air dissects subcutaneously into the anterior mediastinum.</li><li>(2) Crunching sound (Hamman's crunch) is heard on auscultation.</li> </ul><li>Pleural effusion contains food, acid, amylase.</li> </ol> </ol>
</div></html>
<html><a name="HC017030"></a> <br><a name="P017034"></a><div class="PA" style="color: black; "><ol type="1"> <li>Systemic sclerosis and CREST syndrome (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>)</li><li>Achalasia
<blockquote style="color: blue; ">Achalasia: most common neuromuscular disorder of the esophagus</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Bimodal</li><ul> <li>(a) Occurs in those 20 to 40 years old</li><li>(b) Occurs after 60 years of age</li> </ul><li>(2) Men and women affected equally</li><li>(3) Risk for esophageal cancer</li> </ul><li>Pathogenesis</li><ul> <li>(1) Incomplete relaxation of LES</li><li>(2) Destruction of ganglion cells in myenteric plexus</li><ul> <li>(a) Probable autoimmune destruction of myenteric plexus
<blockquote style="color: blue; ">Achalasia: autoimmune destruction ganglion cells myenteric plexus; loss smooth muscle motility</blockquote></li><ul> <li>HLA-DQw1 association</li> </ul><li>(b) Decreases proximal smooth muscle contraction</li><li>(c) Loss of nitric oxide (NO) synthase producing neurons</li><ul> <li>Cause of incomplete relaxation</li> </ul> </ul><li>(3) Dilation of esophagus proximal to LES with absent peristalsis
<blockquote style="color: blue; ">Achalasia: destruction NO synthase producing neurons causes incomplete relaxation LES</blockquote></li><li>(4) Acquired cause is Chagas' disease.</li><ul> <li>Destruction of ganglion cells by amastigotes (lack flagella)</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Nocturnal regurgitation of undigested food
<blockquote style="color: blue; ">Achalasia: nocturnal regurgitation of undigested food</blockquote></li><li>(2) Dysphagia for solids and liquids</li><li>(3) Chest pain and heartburn</li><li>(4) Frequent hiccups</li><li>(5) Nocturnal cough from aspiration</li><li>(6) Difficulty belching</li> </ul><li>Diagnosis</li><ul> <li>(1) Abnormal barium swallow
<blockquote style="color: blue; ">Achalasia barium swallow: dilated, aperistaltic esophagus; beak-like tapering distal end</blockquote></li><ul> <li>Dilated, aperistaltic esophagus with a beak-like tapering at distal end (<span>[[Fig. 17-10|Figure 17-10]]</span>)</li> </ul><li>(2) Abnormal esophageal manometry</li><ul> <li>Detects aperistalsis and failure of LES relaxation</li> </ul> </ul><li>Treatment</li><ul> <li>(1) Nonpharmacologic</li><ul> <li>(a) Pneumatic dilation</li><li>(b) Esophagomyotomy</li> </ul><li>(2) Pharmacologic (short-term)</li><ul> <li>(a) Long-acting nitrates</li><li>(b) Calcium channel blockers</li><li>(c) Botulinum toxin injection</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC017031"></a> <br><a name="P017035"></a><div class="PA" style="color: black; "><ol type="1"> <li>Leiomyoma
<blockquote style="color: blue; ">Leiomyoma: most common benign tumor of esophagus</blockquote></li><ul> <li>Most common benign tumor of esophagus</li> </ul><li>Adenocarcinoma of distal esophagus (<span>[[Fig. 17-11|Figure 17-11]]</span>)</li><ol type="a"> <li>Most common primary cancer of the esophagus in the United States
<blockquote style="color: blue; ">Distal adenocarcinoma of esophagus: most common esophageal cancer</blockquote></li><li>Barrett's esophagus is most common predisposing cause.</li><ul> <li>Prevention of GERD decreases risk for developing adenocarcinoma.</li> </ul> </ol><li>Squamous cell carcinoma</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Most common primary cancer in developing countries</li><ul> <li>Caspian Sea to Northern China</li> </ul><li>(2) More common in blacks than whites</li><li>(3) Occurs in men more often than women</li><li>(4) Risk factors
<blockquote style="color: blue; ">Squamous cell carcinoma: smoking cigarettes most common cause</blockquote></li><ul> <li>(a) Smoking most common cause</li><li>(b) Alcohol abuse, lye strictures</li><li>(c) Achalasia, Plummer-Vinson syndrome</li> </ul><li>(5) Locations</li><ul> <li>(a) Upper third (∼15%)</li><li>(b) Middle third (∼50%) (<span>[[Fig. 17-12|Figure 17-12]]</span>)</li><li>(c) Lower third (∼35%)</li> </ul><li>(6) Spreads to local nodes first and then to liver and lungs</li> </ul><li>Clinical findings
<blockquote style="color: blue; ">Squamous cell carcinoma: dysphagia for solids + weight loss</blockquote></li><ul> <li>(1) Dysphagia for solids initially</li><li>(2) Weight loss of short duration</li><li>(3) Painless enlargement supraclavicular nodes</li><li>(4) Dry cough and hemoptysis
<blockquote style="color: blue; ">Squamous cell carcinoma: symptoms often relate to local invasion</blockquote></li><ul> <li>Suggests tracheal invasion</li> </ul><li>(5) Hoarseness</li><ul> <li>Probable invasion of recurrent laryngeal nerve</li> </ul><li>(6) Odynophagia</li><li>(7) Hypercalcemia</li><ul> <li>Parathyroid harmone-related peptide similar to squamous cancer in lungs</li> </ul> </ul><li>Diagnosis</li><ul> <li>(1) Esophagogram</li><li>(2) Endoscopy</li> </ul><li>Treatment</li><ul> <li>Surgery, radiation therapy, chemotherapy</li> </ul><li>Prognosis</li><ul> <li>Overall 5-year survival rate is 13%.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017033"></a> <br><a name="P017041"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hematemesis (vomiting blood)</li><ol type="a"> <li>Most commonly due to peptic ulcer disease (PUD)
<blockquote style="color: blue; ">PUD: most common cause of hematemesis and melena</blockquote></li><li>Other causes-esophageal varices, hemorrhagic gastritis</li> </ol><li>Melena (dark, tarry stools)</li><ol type="a"> <li>Hemoglobin (Hb) is converted into hematin (black pigment) by acid.
<blockquote style="color: blue; ">Melena: hematin; sign of upper gastrointestinal bleed</blockquote></li><li>Signifies a bleed proximal to duodenojejunal junction (90%)</li> </ol><li>Gastric analysis</li> </ol>
</div></html>
<html><a name="HC017034"></a> <br><a name="PB017002"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Gastric analysis</b> includes measurement of basal acid output (BAO), maximal acid output (MAO), and the BAO:MAO ratio. BAO is the acid output of gastric juice collected via a nasogastric tube over a 1-hour period on an empty stomach. It is normally less than 5 mEq/hour. MAO is the acid output of gastric juice that is collected over 1 hour after pentagastrin stimulation. Normally, it is 5 to 20 mEq/hour. The normal BAO:MAO ratio is 0.20:1.
<blockquote style="color: blue; ">Gastric analysis: measures BAO and MAO</blockquote></div><a name="P017042"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Probable genetic basis</li><li>Occurs in males > females</li><li>Affected fathers or mothers</li><ul> <li>Increased for child with CPS</li> </ul><li>Acquired pyloric obstruction</li><ul> <li>Complication of chronic duodenal ulcer disease with pyloric scarring</li> </ul> </ol><li>Pathophysiology
<blockquote style="color: blue; ">CPS: hypertrophy of pyloric sphincter muscles</blockquote></li><ol type="a"> <li>Progressive hypertrophy of the circular muscles in the pyloric sphincter</li><ul> <li><i>Not</i> present at birth but occurs over the ensuing 3 to 5 weeks</li> </ul><li>Deficiency of NO synthase precipitates the disease</li> </ol><li>Clinical findings</li><ol type="a"> <li>Projectile vomiting of non-bile-stained fluid
<blockquote style="color: blue; ">CPS: vomiting of non-bile-stained fluid</blockquote></li><li>Hypertrophied pylorus is palpated in the epigastrium (70%).</li><ul> <li>Called an "olive"</li> </ul><li>Visible hyperperistalsis</li> </ol><li>Treatment</li><ul> <li>Myotomy if it does <i>not</i> resolve</li> </ul> </ol>
</div></html>
<html><a name="HC017035"></a> <br><a name="P017043"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Gastroparesis: sign of autonomic neuropathy; e.g., diabetes mellitus</blockquote>
<ol type="1"> <li>Decreased stomach motility</li><ol type="a"> <li>Autonomic neuropathy (e.g., diabetes mellitus)</li><li>Previous vagotomy</li> </ol><li>Clinical findings</li><ol type="a"> <li>Early satiety and bloating</li><li>Vomiting of undigested food a few hours after eating
<blockquote style="color: blue; ">Gastroparesis: early satiety; vomiting of undigested food</blockquote></li> </ol><li>Treatment</li><ol type="a"> <li>Small volume frequent feeding</li><li>Metoclopramide</li> </ol> </ol>
</div></html>
<html><a name="HC017036"></a> <br><a name="P017044"></a><div class="PA" style="color: black; "><ol type="1"> <li>Terms</li><ol type="a"> <li>Erosions are a breach in the epithelium of the mucosa.</li><li>Ulcers are a breach in the mucosa with extension into the submucosa or deeper.</li> </ol><li>Causes
<blockquote style="color: blue; ">Hemorrhagic gastritis: NSAIDs most common cause; alcohol second</blockquote></li><ol type="a"> <li>NSAIDs</li><li>Alcohol, <i>Helicobacter pylori</i> (see below)</li><li>CMV (AIDS), smoking</li><li>Burns (called Curling's ulcers)</li><li>CNS injury (called Cushing's ulcers)</li><li>Uremia</li><li><i>Anisakis</i></li><ul> <li>Worm associated with eating raw fish</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Hematemesis</li><li>Melena</li><li>Iron deficiency</li> </ol><li>Treatment (excluding <i>H. pylori</i>)</li><ol type="a"> <li>Nonpharmacologic</li><ul> <li>(1) Avoid mucosal irritants (e.g., NSAIDs, alcohol)</li><li>(2) Cessation of smoking</li> </ul><li>Pharmacologic</li><ul> <li>(1) Misoprostol</li><li>(2) Proton pump inhibitors</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017037"></a> <br><a name="P017045"></a><div class="PA" style="color: black; "><ol type="1"> <li>Type A chronic atrophic gastritis
<blockquote style="color: blue; ">Type A chronic atrophic gastritis: body and fundus; pernicious anemia</blockquote></li><ol type="a"> <li>Involves the body and fundus</li><li>Most often due to pernicious anemia (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li><li>Complications</li><ul> <li>(1) Achlorhydria with hypergastrinemia (loss of negative feedback)</li><li>(2) Macrocytic anemia due to vitamin B<sub>12</sub> deficiency</li><li>(3) Increased risk for gastric adenocarcinoma</li> </ul> </ol><li>Type B chronic atrophic gastritis
<blockquote style="color: blue; ">Type B chronic atrophic gastritis: antrum and pylorus; <i>H. pylori</i></blockquote></li><ol type="a"> <li>Involves the antrum and pylorus</li><li>Epidemiology</li><ul> <li>(1) Most common cause is <i>Helicobacter pylori.</i></li><ul> <li>Gram-negative, curved rod</li> </ul><li>(2) Present in 30% to 50% of population in United States</li><li>(3) Prevalence increases with age.</li><li>(4) Transmitted by fecal-oral/oral-oral route</li><ul> <li>Common in areas of poor sanitation</li> </ul> </ul><li>Pathophysiology</li><ul> <li>(1) Gram-negative, curved rod</li><li>(2) Produces urease, proteases, cytotoxins</li><ul> <li>(a) Urease converts amino groups in proteins to ammonia
<blockquote style="color: blue; "><i>H. pylori:</i> urease producer</blockquote></li><li>(b) Secretion products produce chronic gastritis and PUD.</li> </ul><li>(3) Colonizes mucus layer lining (<span>[[Fig. 17-13|Figure 17-13]]</span>)
<blockquote style="color: blue; "><i>H. pylori:</i> colonizes mucous layer; noninvasive</blockquote></li><ul> <li>(a) Attaches to blood group O receptors on mucosal cells</li><li>(b) <i>Not</i> an invasive bacterium</li> </ul> </ul><li>Microscopic findings</li><ul> <li>(1) Chronic inflammatory infiltrate in the lamina propria</li><li>(2) Intestinal metaplasia (<span>[[Fig. 17-14|Figure 17-14]]</span>)</li><ul> <li>Precursor lesion for adenocarcinoma</li> </ul> </ul><li>Tests to identify <i>H. pylori</i> are highly sensitive and specific.
<blockquote style="color: blue; "><i>H. pylori:</i> chronic atrophic gastritis; intestinal metaplasia precursor for cancer</blockquote></li><ul> <li>(1) Urea breath test</li><ul> <li>(a) Documents active infection</li><li>(b) Sensitivity and specificity > 90%</li> </ul><li>(2) Stool antigen test (excellent screen)
<blockquote style="color: blue; ">Stool antigen test results: + infection; - no infection</blockquote></li><ul> <li>(a) Positive when there is active infection</li><li>(b) Negative when infection has been eradicated</li><li>(c) Sensitivity and specificity > 90%</li> </ul><li>(3) Tests to detect urease in a gastric biopsy</li><ul> <li>Considered gold standard test albeit an invasive test</li> </ul><li>(5) Serologic tests
<blockquote style="color: blue; ">Urea breath test/serology: do not distinguish active vs. old infection</blockquote></li><ul> <li>(a) High sensitivity and specificity</li><li>(b) Do <i>not</i> distinguish current from past infection</li> </ul> </ul><li>Treatment</li><ul> <li>(1) Bismuth, metronidazole, tetracycline, omeprazole</li><li>(2) Omeprazole, amoxicillin, clarithromycin</li><li>(3) Length of treatment varies from 7 to 14 days</li><li>(4) Test of cure is stool antigen test</li><ul> <li>(a) If negative 8 weeks after therapy, infection is cured.</li><li>(b) Does not imply that infection cannot recur</li> </ul> </ul><li>Other disease associations with <i>H. pylori</i></li><ul> <li>(1) Duodenal and gastric ulcers (see later)</li><li>(2) Gastric adenocarcinoma (see later)</li><li>(3) Low-grade B-cell malignant lymphoma (see later)
<blockquote style="color: blue; ">Rx of <i>H. pylori</i> ↓ risk of gastric cancer and lymphoma</blockquote></li> </ul> </ol><li>Menetrier's disease (hypertrophic gastropathy)</li><ol type="a"> <li>Giant rugal folds</li><ul> <li>(1) Due to hyperplasia of mucus-secreting cells</li><li>(2) Causes hypoproteinemia (protein-losing enteropathy)
<blockquote style="color: blue; ">Menetrier's disease: giant rugal folds; ↑ mucus with protein loss; achlorhydria</blockquote></li> </ul><li>Atrophy of parietal cells (achlorhydria)</li><ul> <li>Increased risk for adenocarcinoma</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017038"></a> <br><a name="P017046"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>PUD is most often caused by <i>H. pylori</i> (70%).</li><ul> <li>Other parts of the world > 90%
<blockquote style="color: blue; ">PUD: <i>H. pylori</i> most common cause worldwide</blockquote></li> </ul><li>Eradication of <i>H. pylori</i> markedly reduces PUD recurrence.</li><li>Duodenal ulcers are more common than gastric ulcers.</li><li>Locations</li><ul> <li>(1) Duodenal ulcer first portion of duodenum (>90%)</li><li>(2) Gastric ulcer in lesser curvature near incisura angularis</li> </ul><li>Recurrence rate for untreated PUD ∼60% (>70% in smokers)
<blockquote style="color: blue; ">PUD: duodenal > gastric</blockquote></li> </ol><li>Gross appearance of ulcers</li><ol type="a"> <li>Clean, sharply demarcated, and slightly elevated around the edges</li><li>Most gastric ulcers are benign.</li><ul> <li>Small percentage may be malignant (reason for biopsy).</li> </ul><li>Duodenal ulcers are <i>never</i> malignant.
<blockquote style="color: blue; ">PUD: duodenal ulcers never malignant; gastric ulcers, small percentage malignant</blockquote></li><li>Four layers in sequence are noted in histologic sections of ulcers.</li><ul> <li>(1) Necrotic debris</li><li>(2) Inflammation with a predominance of neutrophils</li><li>(3) Granulation tissue (repair tissue)</li><li>(4) Fibrosis</li> </ul> </ol><li>Comparison of gastric and duodenal ulcers (<span>[[Table 17-2|Table 17-2. COMPARISON OF GASTRIC ULCERS AND DUODENAL ULCERS]]</span> and <span>[[Fig. 17-15|Figure 17-15]]</span>)</li> </ol>
</div></html>
<html><a name="HC017039"></a> <br><a name="P017047"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">ZE syndrome: ↑ gastric, ↑ acid</blockquote>
<ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>Majority (>60%) are malignant pancreatic islet cell tumors.</li><li>Secrete excess gastrin producing hyperacidity
<blockquote style="color: blue; ">ZE syndrome: malignant islet cell tumor secreting gastrin; single or multiple uclers</blockquote></li><li>Sporadic in two thirds of cases</li><li>Ulcers are usually single and in the usual locations; there may be multiple ulcers.</li><li>MEN type I association (20-30% of cases)</li><li>Suspicious for ZE syndrome</li><ul> <li>(1) Multiple ulcers in usual places</li><li>(2) Ulcers resistant to therapy</li><li>(3) Ulcers distal to first portion of duodenum
<blockquote style="color: blue; ">ZE syndrome: PUD + diarrhea</blockquote></li><li>(4) PUD plus diarrhea</li><li>(5) Family history of parathyroid or pituitary tumors</li><li>(6) PUD without <i>H. pylori</i> or history of NSAIDs
<blockquote style="color: blue; ">ZE syndrome: association with MEN I syndrome</blockquote></li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Epigastric pain with weight loss</li><li>Heartburn from GERD (60%)</li><li>Peptic ulceration</li><ul> <li>Most are solitary duodenal ulcers rather than multiple ulcers.</li> </ul><li>Acid hypersecretion with diarrhea</li><li>Maldigestion of food</li><ul> <li>Acid interferes with pancreatic enzyme activity.</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Increased BAO, MAO, and BAO:MAO ratio</li><li>Serum gastrin level > 1000 pg/mL</li> </ol><li>Treatment</li><ul> <li>Chemotherapy and proton pump inhibitors</li> </ul> </ol>
</div></html>
<html><a name="HC017040"></a> <br><a name="P017048"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Gastric polyps: complication chronic gastritis, achlorhydria</blockquote>
<ol type="1"> <li>Complication of chronic gastritis and achlorhydria</li><li>Hyperplastic polyp</li><ol type="a"> <li>Most common type</li><li>Hamartoma with no malignant potential</li> </ol><li>Adenomatous polyp</li><ol type="a"> <li>Neoplastic polyp</li><li>Potential for malignant transformation</li> </ol> </ol>
</div></html>
<html><a name="HC017041"></a> <br><a name="P017049"></a><div class="PA" style="color: black; "><ol type="1"> <li>Leiomyoma
<blockquote style="color: blue; ">Leiomyoma: most common benign tumor in stomach</blockquote></li><ol type="a"> <li>Stomach is most common site.</li><li>May ulcerate or bleed</li> </ol><li>Primary stomach adenocarcinomas</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Decreasing incidence in United States
<blockquote style="color: blue; ">Gastric cancer: increased incidence in Japan</blockquote></li><li>(2) Increasing incidence in Japan</li><li>(3) Increased incidence in blood group A people</li> </ul><li>Intestinal type of gastric adenocarcinoma</li><ul> <li>Most common gastric carcinoma</li> </ul><ul> <li>(1) Risk factors</li><ul> <li>(a) Intestinal metaplasia due to <i>H. pylori</i> (most important)
<blockquote style="color: blue; ">Intestinal metaplasia: precursor lesion for gastric adenocarcinoma</blockquote></li><li>(b) Nitrosamines</li><li>(c) Smoked foods (Japan)</li><li>(d) Diets lacking fruits/vegetables</li><li>(e) Type A chronic atrophic gastritis</li><li>(f) Menetrier's disease</li> </ul><li>(2) Polypoid or ulcerated (<span>[[Fig. 17-16|Figure 17-16]]</span>)</li><li>(3) Locations
<blockquote style="color: blue; ">Gastric cancer: lesser curvature pylorus and antrum most common site</blockquote></li><ul> <li>(a) Lesser curvature of pylorus and antrum (50-60%)</li><li>(b) Cardia (25%), body and fundus</li> </ul> </ul><li>Diffuse type of gastric adenocarcinoma</li><ul> <li>(1) Incidence has remained unchanged.</li><li>(2) <i>Not</i> associated with <i>H. pylori</i></li><li>(3) Diffuse infiltration of malignant cells in the stomach wall</li><ul> <li>(a) Sometimes called "linitis plastica"
<blockquote style="color: blue; ">Diffuse gastric cancer: "linitis plastica"; <i>not</i> related to <i>H. pylori</i></blockquote></li><li>(b) Stomach does <i>not</i> peristalse.</li><li>(c) Signet-ring cells infiltrate the stomach wall (<span>[[Fig. 17-17|Figure 17-17]]</span>).</li><li>(d) Produces Krukenberg tumors of the ovaries
<blockquote style="color: blue; ">Krukenberg tumor: metastatic signet-ring cells to both ovaries</blockquote></li><ul> <li>Hematogenous spread of signet-ring cells to both ovaries</li> </ul> </ul> </ul><li>Clinical findings of gastric adenocarcinoma</li><ul> <li>(1) Cachexia and weight loss (most common; 60%)</li><li>(2) Epigastric pain (50%)</li><li>(3) Vomiting often with melena (20%)</li><li>(4) Metastasis to left supraclavicular node (Virchow's node)
<blockquote style="color: blue; ">Gastric cancer: Virchow's left supraclavicular node metastasis</blockquote></li><li>(5) Paraneoplastic skin lesions (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>)</li><ul> <li>(a) Acanthosis nigricans (see <span>[[Fig. 24-6B|Figure 24-6]]</span>)</li><li>(b) Multiple outcroppings of seborrheic keratoses (Leser-Trélat sign; see <span>[[Fig. 24-6A|Figure 24-6]]</span>)
<blockquote style="color: blue; ">Gastric cancer: acanthosis nigricans; Leser-Trélat sign</blockquote></li> </ul><li>(6) Metastasis to umbilicus (Sister Mary Joseph sign)</li> </ul><li>Common metastatic sites</li><ul> <li>Liver, lung, ovaries</li> </ul><li>Treatment</li><ul> <li>Surgery, local radiation, and chemotherapy</li> </ul><li>Approximately 10% to 15% overall 5-year survival rate</li> </ol><li>Primary gastric malignant lymphoma</li><ol type="a"> <li>Stomach is the most common site for extranodal malignant lymphoma.
<blockquote style="color: blue; ">Gastric lymphoma: most common cause <i>H. pylori</i></blockquote></li><li>Low-grade B-cell lymphoma</li><ul> <li>(1) <i>H. pylori</i>-related</li><li>(2) MALToma (derives from <i>m</i>ucosa-<i>a</i>ssociated <i>l</i>ymphoid <i>t</i>issue)</li> </ul><li>High-grade B- or T-cell lymphomas</li><li>Treatment for <i>H. pylori</i> produces 50% cure rate.</li> </ol> </ol>
</div></html>
![[17.III.A.Signs and symptoms of stomach disease]]
<<tiddler [[17.III.A.Signs and symptoms of stomach disease]]>>
![[17.III.B.Congenital pyloric stenosis (CPS)]]
<<tiddler [[17.III.B.Congenital pyloric stenosis (CPS)]]>>
![[17.III.C.Gastroparesis]]
<<tiddler [[17.III.C.Gastroparesis]]>>
![[17.III.D.Acute hemorrhagic (erosive) gastritis]]
<<tiddler [[17.III.D.Acute hemorrhagic (erosive) gastritis]]>>
![[17.III.E.Chronic atrophic gastritis]]
<<tiddler [[17.III.E.Chronic atrophic gastritis]]>>
![[17.III.F.Peptic ulcer disease (PUD)]]
<<tiddler [[17.III.F.Peptic ulcer disease (PUD)]]>>
![[17.III.G.Zollinger-Ellison (ZE) syndrome]]
<<tiddler [[17.III.G.Zollinger-Ellison (ZE) syndrome]]>>
![[17.III.H.Gastric polyps]]
<<tiddler [[17.III.H.Gastric polyps]]>>
![[17.III.I.Gastric tumors]]
<<tiddler [[17.III.I.Gastric tumors]]>>
<html><a name="HC017043"></a> <br><a name="P017055"></a><div class="PA" style="color: black; "><ol type="1"> <li>Colicky pain</li><ol type="a"> <li>Pain followed by a pain-free interval
<blockquote style="color: blue; ">Colicky pain: symptom of bowel obstruction</blockquote></li><ul> <li>Accompanied by constipation and inability to pass gas</li> </ul><li>Symptom of bowel obstruction</li><ul> <li>Example-adhesions from previous surgery</li> </ul> </ol><li>Diarrhea</li><ol type="a"> <li>Sign of</li><ul> <li>(1) Infection</li><li>(2) Malabsorption</li><li>(3) Osmotic diarrhea</li> </ul><li>If bloody, may be a sign of</li><ul> <li>(1) Infarction</li><li>(2) Volvulus</li><li>(3) Dysentery</li> </ul> </ol><li>Anemia; malabsorption of</li><ol type="a"> <li>Iron</li><li>Folate</li><li>Vitamin B<sub>12</sub></li> </ol> </ol>
</div></html>
<html><a name="HC017044"></a> <br><a name="P017056"></a><div class="PA" style="color: black; "><ol type="1"> <li>Diarrhea</li><ol type="a"> <li>Sign of</li><ul> <li>(1) Infection</li><li>(2) Laxative abuse</li><li>(3) Inflammatory bowel disease</li> </ul><li>If bloody, may be a sign of infarction or dysentery</li> </ol><li>Dysentery
<blockquote style="color: blue; ">Dysentery: bloody diarrhea with mucus</blockquote></li><ol type="a"> <li>Refers to bloody diarrhea with mucus</li><li>Infection
<blockquote style="color: blue; ">Melanosis coli: black bowel from laxatives</blockquote></li> </ol><li>Pain</li><ol type="a"> <li>Inflammatory bowel disease</li><li>Ischemic colitis</li><li>Diverticulitis</li><li>Appendicitis</li><li>Peritonitis</li> </ol><li>Tenesmus</li><ol type="a"> <li>Painful, ineffective straining at stool</li><li>Commonly present in ulcerative colitis</li> </ol><li>Iron deficiency</li><ul> <li>Consider polyps, colorectal cancer</li> </ul><li>Hematochezia</li><ol type="a"> <li>Massive loss of whole blood per rectum)</li><li>Causes
<blockquote style="color: blue; ">Hematochezia: sigmoid diverticulosis, angiodysplasia</blockquote></li><ul> <li>(1) Sigmoid diverticulosis (most common)</li><li>(2) Angiodysplasia</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017045"></a> <br><a name="PB017003"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Lactase deficiency</b> is a common genetic defect in Native Americans, Asians, and blacks. Colon anaerobes degrade undigested lactose into lactic acid and H<sub>2</sub> gas leading to abdominal distention with explosive diarrhea. Treatment is to avoid dairy products.
<blockquote style="color: blue; ">Lactase deficiency: disaccharidase deficiency in brush border; avoid dairy products</blockquote></div><a name="P017057"></a><div class="PA" style="color: black; "><ol type="1"> <li>Diarrhea</li><ol type="a"> <li>More than 250 g of stool per day</li><li>Acute diarrhea is defined as less than 3 weeks, chronic diarrhea over 4 weeks</li><li>Invasive, osmotic, secretory types (<span>[[Table 17-3|Table 17-3. TYPES OF DIARRHEA]]</span>)
<blockquote style="color: blue; ">Types of diarrhea: osmotic, secretory, invasive</blockquote></li> </ol><li>Important screening tests</li><ol type="a"> <li>Fecal smear for leukocytes (e.g., invasive diarrhea)
<blockquote style="color: blue; ">Fecal smear for leukocytes: screen for invasive diarrhea</blockquote></li><li>Stool osmotic gap</li><ul> <li>(1) 300 mOsm/kg (value used to represent normal POsm) - 2 × (random stool Na<sup>+</sup> + random stool K<sup>+</sup>)</li><li>(2) Gap < 50 mOsm/kg from POsm is a secretory diarrhea.
<blockquote style="color: blue; ">Secretory diarrhea: loss of isotonic fluid</blockquote></li><ul> <li>Indicates that diarrheal fluid approximates POsm</li> </ul><li>(3) Gap > 100 mOsm/kg from POsm is an osmotic diarrhea.
<blockquote style="color: blue; ">Osmotic diarrhea: loss of hypotonic fluid</blockquote></li><ul> <li>Indicates a hypotonic loss of stool due to presence of osmotically active substances
<blockquote style="color: blue; ">Stool osmotic gap: distinguishes secretory from osmotic diarrhea</blockquote></li> </ul> </ul> </ol><li>Summary table of microbial pathogens causing diarrhea (<span>[[Table 17-4|Table 17-4. MICROBIAL PATHOGENS CAUSING DIARRHEA]]</span> and <span>[[Fig. 17-18|Figure 17-18]]</span>)</li> </ol>
</div></html>
<html><a name="HC017046"></a> <br><a name="P017058"></a><div class="PA" style="color: black; "><ol type="1"> <li>Definition</li><ol type="a"> <li>Increased fecal excretion of fat plus</li><li>Concurrent deficiencies of fat-soluble vitamins, minerals, carbohydrates, and proteins
<blockquote style="color: blue; ">Causes malabsorption: pancreatic insufficiency, bile salt/acid deficiency, small bowel disease</blockquote></li> </ol><li>Pathogenesis</li><ul> <li>Pancreatic insufficiency, bile salt/acid deficiency, small bowel disease</li> </ul><li>Pancreatic insufficiency</li><ol type="a"> <li>Most often caused by chronic pancreatitis</li><ul> <li>Most commonly due to alcohol in adults and cystic fibrosis in children</li> </ul><li>Pathogenesis</li><ul> <li>(1) Maldigestion of fats</li><ul> <li>(a) Due to diminished lipase activity</li><li>(b) Undigested neutral fats and fat droplets are in stool.</li> </ul><li>(2) Maldigestion of proteins</li><ul> <li>(a) Due to diminished trypsin
<blockquote style="color: blue; ">Pancreatic insufficiency: malabsorption of fat and proteins, not carbohydrates</blockquote></li><li>(b) Undigested meat fibers are in stool.</li> </ul><li>(3) Carbohydrate digestion is <i>not</i> affected.</li><ul> <li>(a) Amylase is present in salivary glands.</li><li>(b) Disaccharidases are present in the brush border of intestinal epithelium.</li> </ul> </ul> </ol><li>Bile salt/acid deficiency
<blockquote style="color: blue; ">Bile salts/acids: required to micellarize monoglycerides and fatty acids</blockquote></li><ol type="a"> <li>Bile salts/acid are required to micellarize monoglycerides and fatty acids.</li><li>Etiology and pathogenesis</li><ul> <li>(1) Inadequate synthesis of bile salts/acids from cholesterol (e.g., cirrhosis)</li><li>(2) Intrahepatic/extrahepatic blockage of bile</li><ul> <li>Examples-primary biliary cirrhosis, stone in common bile duct</li> </ul><li>(3) Bacterial overgrowth in small bowel with destruction of bile salts/acids</li><ul> <li>Examples-small bowel diverticula, autonomic neuropathy</li> </ul><li>(4) Excess binding of bile salts</li><ul> <li>Example-cholestyramine</li> </ul><li>(5) Terminal ileal disease</li><ul> <li>(a) Prevents recycling of bile salts/acids</li><li>(b) Examples-Crohn's disease, resection of ileum</li> </ul> </ul> </ol><li>Small bowel disease
<blockquote style="color: blue; ">Small bowel disease: loss of villous absorptive surface</blockquote></li><ol type="a"> <li>Villi are required to reabsorb micelles into enterocytes.</li><ul> <li>Villi increase the absorptive surface of the small intestine.</li> </ul><li>Etiology and pathogenesis</li><ul> <li>(1) Inability to reabsorb micelles</li><ul> <li>(a) Due to loss of villous surface</li><li>(b) Examples-celiac disease (see later), Whipple's disease</li> </ul><li>(2) Lymphatic obstruction</li><ul> <li>Examples-Whipple's disease, abetalipoproteinemia (see <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)</li> </ul> </ul> </ol><li>General screening tests for fat malabsorption
<blockquote style="color: blue; ">General screening tests for malabsorption: stool for fat, serum beta carotene</blockquote></li><ol type="a"> <li>Quantitative stool for fat</li><ul> <li>(1) Best screening test</li><li>(2) 72-hour collection of stool</li><li>(3) Positive test > 7 g of fat/24 hours.</li> </ul><li>Qualitative stool for fat</li><ul> <li>(1) Stains are used to identify fat in stool.</li><li>(2) Lacks sensitivity</li> </ul><li>Decreased serum beta carotene</li><ul> <li>Precursor for fat-soluble retinoic acid (vitamin A)</li> </ul><li><span style="font-variant:small-caps;">d</span>-Xylose screening test
<blockquote style="color: blue; "><span style="font-variant:small-caps;">d</span>-Xylose: decreased reabsorption indicates small bowel disease</blockquote></li><ul> <li>(1) Xylose does <i>not</i> require pancreatic enzymes for absorption.</li><li>(2) Lack of reabsorption of orally administered xylose</li><ul> <li>Indicates small bowel disease</li> </ul> </ul> </ol><li>Tests to evaluate pancreatic insufficiency</li><ol type="a"> <li>Serum immunoreactive trypsin
<blockquote style="color: blue; ">Serum immunoreactive trypsin: excellent newborn screen for cystic fibrosis</blockquote></li><ul> <li>(1) Trypsin is specific for the pancreas.</li><li>(2) Serum immunoreactive trypsin in chronic pancreatitis</li><ul> <li>Decreased concentration; excellent serum for cystic fibrosis</li> </ul> </ul><li>CT scan of pancreas shows dystrophic calcification.</li><ul> <li>Sign of chronic pancreatitis</li> </ul><li>Functional tests</li><ul> <li>(1) Secretin stimulation test (requires instrumentation)</li><ul> <li>Tests ability of pancreas to secrete fluids and electrolytes
<blockquote style="color: blue; ">Chronic pancreatitis: CT scan dystrophic calcification</blockquote></li> </ul><li>(2) Bentiromide test</li><ul> <li>Tests ability of pancreatic chymotrypsin to cleave orally administered bentiromide to para-aminobenzoic acid (measured in urine)</li> </ul> </ul> </ol><li>Tests for bile salt/acid deficiency</li><ol type="a"> <li>Total bile acids can be measured.</li><ul> <li>Decreased in liver disease (e.g., cirrhosis)
<blockquote style="color: blue; ">Tests pancreatic insufficiency: secretin stimulation; bentiromide</blockquote></li> </ul><li>Bile breath test (oral radioactive test)</li><ul> <li>Decreased amount radioactive cholylglycine in breath indicates bacterial overgrowth or terminal ileal disease</li> </ul> </ol><li>Tests for bacterial overgrowth</li><ol type="a"> <li><sup>14</sup>C-xylose</li><ul> <li>(1) Most sensitive/specific test</li><li>(2) Measures <sup>14</sup>CO<sub>2</sub> in the breath</li> </ul><li>Lactulose-H<sub>2</sub></li><ul> <li>Measures H<sub>2</sub> in the breath</li> </ul> </ol><li>Clinical findings in malabsorption
<blockquote style="color: blue; ">Tests bile salt/acid deficiency: serum bile acids, bile breath test</blockquote></li><ol type="a"> <li>Steatorrhea</li><ul> <li>Excessive, large, sticky, stools that float</li> </ul><li>Fat-soluble vitamin deficiencies (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>)</li><ul> <li>Fat-soluble vitamins are A, D, E, K</li> </ul><li>Water-soluble vitamin deficiencies (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>)</li><ul> <li>Particularly folate and vitamin B<sub>12</sub></li> </ul><li>Combined anemias (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li><ul> <li>Example-folate and iron deficiency</li> </ul><li>Ascites and pitting edema (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li><ul> <li>Due to hypoproteinemia</li> </ul> </ol><li>Celiac disease
<blockquote style="color: blue; ">Clinical: steatorrhea, fat-/water-soluble vitamin deficiencies, anemia, ascites</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Inappropriate immune response to gluten in wheat products</li><ul> <li>Also related proteins in rye and barley</li> </ul><li>(2) Prevalence of 1% in North America</li><li>(3) Common in whites; uncommon in blacks and Asians</li><li>(4) Occurs at any age</li><ul> <li>(a) Highest incidence in infancy</li><ul> <li>First introduction to gluten products</li> </ul><li>(b) Third decade</li><ul> <li>Frequent association with pregnancy</li> </ul><li>(c) Seventh decade</li> </ul><li>(5) Associations
<blockquote style="color: blue; ">Celiac disease: immune disease directed against gluten</blockquote></li><ul> <li>(a) Dermatitis herpetiformis</li><li>(b) Autoimmune disease</li><ul> <li>Hashimoto's thyroiditis, primary biliary cirrhosis</li> </ul><li>(c) Type 1 diabetes mellitus</li><li>(d) IgA deficiency</li><li>(e) Down syndrome, Turner's syndrome</li> </ul> </ul><li>Pathogenesis</li><ul> <li>(1) Multiorgan autoimmune disease</li><li>(2) Inappropriate T-cell and IgA-mediated response against gluten in genetically predisposed persons</li><ul> <li>Association with HLA-DQ2 (95%) and HLA-DQ8 (5%)</li> </ul><li>(3) Timing and dose when gluten introduced in the diet is important.</li><li>(4) Tissue transglutaminase (tTG; deamidating enzyme) in the lamina propria has a pivotal role.
<blockquote style="color: blue; ">Celiac disease: greatest association with dermatitis herpetiformis</blockquote></li><ul> <li>(a) It deaminates mucosally absorbed gluten to produce deaminated and negatively charged gluten peptides.</li><li>(b) It also enhances the immunostimulatory effect of the deaminated gluten peptides.</li><li>(c) These peptides are phagocytosed by antigen-processing cells in the lamina propria.</li><li>(d) They are presented in complex with HLA-DQ2 or -DQ8 to gluten-specific CD4 T-helper cells.</li><li>(e) CD4 T cells produce cytokines that release matrix proteases causing cell death and degradation in the epithelial cells in the villi.</li> </ul> </ul><li>Important diagnostic antibodies</li><ul> <li>(1) Anti-tissue transglutaminase IgA (most important), IgG antibodies</li><ul> <li>(a) Sensitivity and specificity 98%</li><li>(b) Excellent screening test</li> </ul><li>(2) Anti-endomysial (EMA) IgA antibodies</li><ul> <li>(a) Sensitivity and specificity 100%</li><li>(b) Excellent screening test</li> </ul><li>(3) Antigliadin IgA, IgG antibodies
<blockquote style="color: blue; ">Celiac disease: tTG has pivotal role</blockquote></li><ul> <li>(a) Sensitivity 80%, specificity 85%</li><li>(b) Moderately good screening test</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Steatorrhea</li><li>(2) Weight loss
<blockquote style="color: blue; ">Celiac disease: ↑ tTG, EMA, gliadin IgA antibodies</blockquote></li><li>(3) Failure to thrive in infants and children</li><li>(4) Pallor due to anemia (often combined anemias)</li><li>(5) Dermatitis herpetiformis (<span>[[Fig. 17-19|Figure 17-19]]</span>; refer to <span macro="tag [[24 Skin Disorders]] [[Chapter 24]]"></span>)</li><ul> <li>(a) Considered to be a form of celiac disease</li><li>(b) Villous atrophy in 75% of cases with or without diarrhea</li><li>(c) Low levels of above diagnostic antibodies</li> </ul><li>(6) Findings related to water-soluble and fat-soluble vitamin deficiencies (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>)</li><li>(7) Other systemic findings</li><ul> <li>(a) Bone-osteoporosis, arthritis</li><li>(b) CNS-seizures, depression</li><li>(c) Reproductive-delayed puberty, miscarriages, infertility</li> </ul> </ul><li>Diagnosis</li><ul> <li>(1) Above diagnostic antibodies
<blockquote style="color: blue; ">Celiac disease: steatorrhea, weight loss</blockquote></li><li>(2) Endoscopic biopsy (<span>[[Fig. 17-20|Figure 17-20]]</span>)</li><ul> <li>(a) Flattened villi, particularly in duodenum and jejunum</li><li>(b) Hyperplastic glands with intense lymphocytic inflammation</li> </ul> </ul><li>Treatment</li><ul> <li>(1) Gluten-free diet
<blockquote style="color: blue; ">Celiac disease: flattened villi; hyperplastic glands</blockquote></li><li>(2) Correct nutritional deficiencies</li><ul> <li>All fat-soluble vitamins; folate, vitamin B<sub>12</sub>; calcium</li> </ul><li>(3) Corticosteroids in refractory cases</li> </ul> </ol><li>Whipple's disease</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Occurs in men more commonly than women</li><li>(2) Peak incidence in middle age</li><li>(3) Caused by <i>Tropheryma whippelii</i>
<blockquote style="color: blue; ">Celiac disease: gluten free diet</blockquote></li><ul> <li>Identified by polymerase chain reaction</li> </ul><li>(4) Microscopic</li><ul> <li>(a) Blunting of villi</li><li>(b) Foamy PAS-positive macrophages in lamina propria
<blockquote style="color: blue; ">Whipple's disease: foamy macrophages</blockquote></li><li>(c) Macrophages obstruct lymphatics and reabsorption of chylomicrons</li><ul> <li>Malabsorption of fats</li> </ul> </ul><li>(5) Clinical findings</li><ul> <li>(a) Steatorrhea</li><li>(b) Fever</li><li>(c) Recurrent polyarthritis</li><li>(d) Generalized lymphadenopathy</li><li>(e) Increased skin pigmentation</li> </ul><li>(6) Treatment with antibiotics</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017047"></a> <br><a name="P017059"></a><div class="PA" style="color: black; "><ol type="1"> <li>Small bowel (SB) obstruction is the most common site for obstruction.</li><li>Radiographic findings
<blockquote style="color: blue; ">SB obstruction: bowel distention; air/fluid levels</blockquote></li><ol type="a"> <li>Bowel distention</li><li>Air-fluid levels with a step-ladder appearance (<span>[[Fig. 17-21|Figure 17-21]]</span>)</li><li>Absence of air distal to obstruction</li> </ol><li>Causes of obstruction (<span>[[Table 17-5|Table 17-6. HERNIAS]]</span> and <span>[[Figs. 17-22|Figure 17-22]]</span> and <span>[[17-23|Figure 17-23]]</span>)
<blockquote style="color: blue; ">Colicky pain: pain alternating with pain free intervals; sign of bowel obstruction</blockquote></li><li>Clinical findings</li><ol type="a"> <li>Colicky pain</li><ul> <li>Severe pain alternating with pain free intervals</li> </ul><li>Abdominal distention</li><li>No rebound tenderness</li><li>Tympanitic to percussion</li><li>High-pitched tinkling sounds</li> </ol><li>Treatment is surgery.
<blockquote style="color: blue; ">Adhesions from previous surgery: most common cause of small bowel obstruction</blockquote></li> </ol>
</div></html>
<html><a name="HC017048"></a> <br><a name="P017060"></a><div class="PA" style="color: black; "><ol type="1"> <li>Mechanisms predisposing to acquired hernias</li><ol type="a"> <li>Increased intra-abdominal pressure (e.g., coughing, heavy weight lifting)</li><li>Weakness in abdominal wall</li> </ol><li>Types of hernias (<span>[[Table 17-6|Table 17-6. HERNIAS]]</span> and <span>[[Figs. 17-24|Figure 17-24]]</span> and <span>[[17-25|Figure 17-25]]</span>)
<blockquote style="color: blue; ">Indirect inguinal hernia: most common hernia</blockquote></li> </ol>
</div></html>
<html><a name="HC017049"></a> <br><a name="P017061"></a><div class="PA" style="color: black; "><ol type="1"> <li>Small bowel is more likely than large bowel to have ischemic damage.</li><ol type="a"> <li>Most of the small bowel is supplied by the superior mesenteric artery (SMA).</li><li>Areas supplied by SMA</li><ul> <li>(1) Most of the small bowel</li><li>(2) Ascending and transverse colon</li><li>(3) SMA and inferior mesenteric artery (IMA) overlap at the splenic flexure.
<blockquote style="color: blue; ">SMA and IMA: watershed area</blockquote></li><ul> <li>Splenic flexure is a watershed area (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>).</li> </ul> </ul> </ol><li>Types of infarctions</li><ol type="a"> <li>Transmural</li><ul> <li>(1) Full-thickness hemorrhagic infarction</li><ul> <li>Usually involves all or part of the small bowel</li> </ul><li>(2) Usually due to occlusion of SMA
<blockquote style="color: blue; ">Occlusion of SMA: most common cause of small bowel infarction</blockquote></li> </ul><li>Mural and mucosal infarctions</li><ul> <li>Usually occur in hypoperfusion states (e.g., shock)</li> </ul> </ol><li>Causes of acute ischemia involving small bowel</li><ol type="a"> <li>Acute mesenteric ischemia (50% of cases)
<blockquote style="color: blue; ">Atrial fibrillation: most common arrhythmia associated with systemic embolization</blockquote></li><ul> <li>(1) Embolism from the left side of the heart to the SMA</li><ul> <li>Atrial fibrillation is the most common predisposing arrhythmia.</li> </ul><li>(2) Thrombosis of the SMA (<span>[[Fig. 17-26|Figure 17-26]]</span>)</li> </ul><li>Nonocclusive ischemia (25% of cases)</li><ul> <li>(1) Hypotension secondary to heart failure (most common)</li><li>(2) Hypovolemic shock</li><li>(3) Patient taking digitalis (? vasospasm)</li> </ul><li>Mesenteric vein thrombosis (25% of cases)</li><ul> <li>(1) Thrombosis states</li><ul> <li>(a) Polycythemia vera</li><li>(b) Antiphospholipid syndrome</li> </ul><li>(2) Extension of renal cell carcinoma into vena cava</li> </ul> </ol><li>Clinical and radiographic findings of small bowel infarction</li><ol type="a"> <li>Sudden onset of diffuse abdominal pain</li><ul> <li>Pain disproportionate to physical findings</li> </ul><li>Bowel distention</li><li>Bloody diarrhea
<blockquote style="color: blue; ">Small bowel infarction: sudden onset diffuse abdominal pain, bloody diarrhea</blockquote></li><ul> <li>Usually occurs in an elderly patient</li> </ul><li>Absent bowel sounds (ileus)</li><li><i>No</i> rebound tenderness (peritonitis) early in infarction</li><li>Profound neutrophilic leukocytosis</li><li>Positive stool guaiac
<blockquote style="color: blue; ">Small bowel infarction: distention, absent bowel sounds, no rebound tenderness</blockquote></li><li>Radiographic findings</li><ul> <li>(1) "Thumbprint sign" due to edema in bowel wall</li><li>(2) Bowel distention with air-fluid levels similar to bowel obstruction</li> </ul><li>Abdominal CT scan has 90% sensitivity.</li><li>Treatment</li><ul> <li>(1) Surgery for embolic disease</li><li>(2) Thrombotic disease</li><ul> <li>Anticoagulation and surgery if necessary</li> </ul> </ul> </ol><li>Ischemic colitis</li><ol type="a"> <li>Involves the splenic flexure of the large bowel</li><ul> <li>Watershed area (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li> </ul><li>Atherosclerotic narrowing of SMA causes mesenteric angina.
<blockquote style="color: blue; ">Ischemic colitis: mesenteric angina after eating → fear of eating and weight loss</blockquote></li><ul> <li>(1) Severe pain occurs in splenic flexure shortly after eating.</li><li>(2) Patient loses weight for fear of pain related to eating.</li> </ul><li>Clinical findings</li><ul> <li>(1) History compatible with mesenteric angina
<blockquote style="color: blue; ">Ischemic colitis with infarction: mesenteric angina + bloody diarrhea</blockquote></li><li>(2) Pain localized to the splenic flexure</li><ul> <li>Accompanied by bloody diarrhea due to mucosal or mural infarction</li> </ul><li>(3) Barium study shows "thumb-printing" of the colonic mucosa (<span>[[Fig. 17-27|Figure 17-27]]</span>).</li><ul> <li>Due to edema of the mucosa</li> </ul> </ul><li>Normal repair of infarction site may result in fibrosis.</li><ul> <li>Common cause of ischemic strictures and obstruction</li> </ul> </ol><li>Angiodysplasia
<blockquote style="color: blue; ">Angiodysplasia: dilation cecal submucosal venules; hematochezia</blockquote></li><ol type="a"> <li>Dilation of mucosal and submucosal venules in cecum and right colon (<span>[[Fig. 17-28|Figure 17-28]]</span>)</li><ul> <li>(1) Usually occurs in elderly individuals</li><li>(2) Vascular ectasias in the cecum increase with age.</li> </ul><li>Increased wall stress in the cecum stretches the venules.
<blockquote style="color: blue; ">Angiodysplasia: second most common cause hematochezia</blockquote></li><li>Clinical findings</li><ul> <li>(1) Hematochezia</li><li>(2) Association with von Willebrand disease (vWD) and calcific aortic stenosis</li> </ul><li>Diagnose with colonoscopy and angiography
<blockquote style="color: blue; ">Angiodysplasia: association with vWD and calcific aortic stenosis</blockquote></li><li>Treatment</li><ul> <li>(1) Colonoscopy</li><ul> <li>(a) Identifies lesions</li><li>(b) Cautery of lesions</li> </ul><li>(2) Angiography localizes the disease</li><li>(3) Right hemicolectomy</li><li>(4) Correction of aortic stenosis (if present)</li><ul> <li>Bleeding often abates</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC017050"></a> <br><a name="P017062"></a><div class="PA" style="color: black; "><ol type="1"> <li>Meckel diverticulum</li><ol type="a"> <li>Vitelline (omphalomesenteric) duct remnant</li><ul> <li>(1) True diverticulum (<span>[[Fig. 17-29|Figure 17-29]]</span>)</li><li>(2) Mnemonic: 2 inches long, 2 feet from ileocecal valve, 2% of population, 2% symptomatic</li> </ul><li>Contains pancreatic rests and heterotopic gastric mucosa</li><ul> <li>Increase the risk for bleeding
<blockquote style="color: blue; ">Newborn with fecal material in umbilical area: persistence of vitelline duct</blockquote></li> </ul><li>Clinical findings</li><ul> <li>(1) Newborn finding</li><ul> <li>Fecal material in umbilical area due to persistence of vitelline duct</li> </ul><li>(2) Bleeding (most common finding)
<blockquote style="color: blue; ">Meckel diverticulum: bleeding most common complication</blockquote></li><ul> <li>Common cause of iron deficiency in newborns and young children</li> </ul><li>(3) Diverticulitis</li><ul> <li>Clinically impossible to distinguish Meckel diverticulitis from appendicitis
<blockquote style="color: blue; ">Meckel diverticulitis: mimics acute appendicitis</blockquote></li> </ul> </ul><li>Diagnosis</li><ul> <li><sup>99m</sup>Tc nuclear scan identifies parietal cells in ectopic gastric mucosa.</li> </ul><li>Treatment is surgery.</li> </ol><li>Small bowel pulsion diverticula
<blockquote style="color: blue; ">SB diverticula: duodenum most common site; diverticulitis, bacterial overgrowth</blockquote></li><ol type="a"> <li>Duodenum is most common site.</li><ul> <li>Wide-mouthed diverticula suggests systemic sclerosis.</li> </ul><li>Complications</li><ul> <li>(1) Diverticulitis (danger of perforation)</li><li>(2) Bacterial overgrowth</li><ul> <li>May produce bile salt deficiency and vitamin B<sub>12</sub> deficiency</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC017051"></a> <br><a name="PB017004"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Colovesical fistula</b> (connection between large bowel and the bladder) is a common fistula in the gastrointestinal tract. It is associated with pneumaturia (air in urine) and recurrent urinary tract infections.</div><a name="P017063"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Incidence in general public is 35% to 50%</li><li>Incidence increases with age</li><li>Most common site for diverticula in entire gastrointestinal tract</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Due to a low-fiber diet with increased constipation
<blockquote style="color: blue; ">Sigmoid diverticular disease: constipation most common cause</blockquote></li><li>Sigmoid colon most common site (<span>[[Figs. 17-30|Figure 17-30]]</span> and <span>[[17-31|Figure 17-31]]</span>)</li><li>Area of weakness is where vasa recta penetrate the muscular propria.</li><ul> <li>Diverticulum is juxtaposed to a blood vessel.</li> </ul><li>Associations</li><ul> <li>(1) Marfan syndrome</li><li>(2) Ehlers-Danlos syndrome</li><li>(3) Adult polycystic kidney disease</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Diverticulitis is the most common complication.
<blockquote style="color: blue; ">Sigmoid diverticular disease: diverticulitis most common complication</blockquote></li><ul> <li>(1) Caused by stool impacted (fecalith) in diverticulum sac</li><ul> <li>Produces ulceration and ischemia</li> </ul><li>(2) Clinical findings</li><ul> <li>(a) Fever</li><li>(b) Diarrhea initially followed by constipation</li><li>(c) Left lower quadrant pain ("left-sided appendicitis")
<blockquote style="color: blue; ">Sigmoid diverticulitis: "left-sided appendicitis"</blockquote></li><li>(d) Tender mass can be palpated in some cases</li> </ul><li>(3) Best diagnosed with CT scan or water-soluble barium study
<blockquote style="color: blue; ">Sigmoid diverticulitis: CT scan</blockquote></li><li>(4) Increased risk for perforation and abscess formation</li> </ul><li>Diverticulosis</li><ul> <li>Painless bleeding; often massive (hematochezia)</li> </ul> </ol><li>Other complications</li><ol type="a"> <li>Most common cause of hematochezia
<blockquote style="color: blue; ">Sigmoid diverticular disease: most common cause hematochezia and fistulas</blockquote></li><ul> <li>(1) Refers to diverticulosis <i>not</i> diverticulitis</li><li>(2) Scarring of the vessel in diverticulitis prevents bleeding.</li> </ul><li>Most common cause of fistulas (connection between hollow structures)</li> </ol><li>Treatment</li><ol type="a"> <li>Nonpharmacologic</li><ul> <li>Increase fiber in diet to prevent constipation</li> </ul><li>Antibiotics for acute disease</li><li>Colonic resection in selected cases</li><ul> <li>Examples-repeated episodes diverticulitis; bleeding that does not stop; abscess/fistula formation; obstruction</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017052"></a> <br><a name="P017064"></a><div class="PA" style="color: black; "><ol type="1"> <li>Ulcerative colitis</li><ol type="a"> <li>Most common inflammatory bowel disease</li><li>Chronic relapsing ulceroinflammatory disease</li><li>Ulcerations are in continuity (<span>[[Fig. 17-32|Figure 17-32]]</span>).
<blockquote style="color: blue; ">Ulcerative colitis: mucosal/submucosal ulcerations</blockquote></li><ul> <li>Ulcerations are limited to the mucosa and submucosa of rectum and colon (<span>[[Fig. 17-33|Figure 17-33]]</span>).</li> </ul> </ol><li>Crohn's disease</li><ol type="a"> <li>Chronic granulomatous, ulceroconstrictive disease</li><li>Transmural inflammation (<span>[[Fig. 17-34|Figure 17-34]]</span>)</li><li>Noncaseating granulomas (60% of cases; <span>[[Fig. 17-35|Figure 17-35]]</span>)
<blockquote style="color: blue; ">Crohn's disease: transmural inflammation</blockquote></li><ul> <li>Discontinuous spread throughout entire gastrointestinal tract</li> </ul> </ol><li>Indeterminate colitis (10%)</li><ul> <li>Features of ulcerative colitis and Crohn's disease</li> </ul><li>Summary of ulcerative colitis and Crohn's disease (<span>[[Table 17-7|Table 17-7. COMPARISON OF ULCERATIVE COLITIS AND CROHN'S DISEASE]]</span>; see <span>[[Figs. 17-32|Figure 17-32]]</span> to <span>[[17-35|Figure 17-35]]</span>)</li> </ol>
</div></html>
<html><a name="HC017053"></a> <br><a name="P017065"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Intrinsic colonic motility disorder</li><ul> <li>(1) Possible loss of tolerance to gastrointestinal flora</li><li>(2) Possible genetic factors</li><li>(3) Environmental triggers
<blockquote style="color: blue; ">IBS: intrinsic colonic motility disorder</blockquote></li> </ul><li>Most common functional bowel disorder</li><li>Responsible for >50% of referrals to gastroenterologists
<blockquote style="color: blue; ">IBS: most common functional bowel disorder</blockquote></li><li>Occurs more often in females than males</li><li>Small bowel bacterial overgrowth may be present in some cases.</li><li>Risk factors</li><ul> <li>(1) History of childhood sexual abuse</li><li>(2) Domestic abuse in women</li><li>(3) Increased stress, depression, personality disorder</li> </ul> </ol><li>Alternating bouts of diarrhea and constipation</li><ol type="a"> <li>Abdominal pain and bloating relieved by defecation
<blockquote style="color: blue; ">IBS: alternating bouts constipation/diarrhea; increased mucus in stool</blockquote></li><li>Stools accompanied by mucus</li><li>Abnormal defecation</li><ul> <li>(1) Straining</li><li>(2) Sense of incomplete evacuation</li> </ul> </ol><li>Normal flexible sigmoidoscopy/colonoscopy</li><li>Treatment</li><ol type="a"> <li>Nonpharmacologic</li><ul> <li>(1) Mainstay is adequate fiber intake.
<blockquote style="color: blue; ">IBN: mainstay is adequate fiber intake</blockquote></li><li>(2) Eliminate foods that aggravate</li><ul> <li>Examples-coffee, fatty foods, dairy products</li> </ul> </ul><li>Pharmacologic</li><ul> <li>(1) Antispasmodics-anticholinergics</li><ul> <li>Example-dicyclomine</li> </ul><li>(2) Loperamide is effective for diarrhea.</li><ul> <li>Serotonin type 3 receptor antagonist</li> </ul><li>(3) Lubiprostone (chloride channel activator) is effective for constipation.</li><li>(4) Rifaximin is effective if small bowel bacterial overgrowth is documented.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC017054"></a> <br><a name="P017066"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Small bowel: least common site for malignancy in GI tract</blockquote>
<ul> <li>Small bowel is the <i>least</i> common site in the gastrointestinal tract for a primary malignancy.</li><ol type="1"> <li>Primary adenocarcinoma</li><ul> <li>Duodenum most common site</li> </ul><li>Carcinoid tumor</li><ol type="a"> <li>Most common small bowel malignancy
<blockquote style="color: blue; ">Carcinoid tumors: malignant neuroendocrine tumors</blockquote></li><li>Neuroendocrine tumor</li><ul> <li>(1) Contains neurosecretory granules visible on electron microscopy</li><li>(2) Carcinoid tumors are malignant.</li><li>(3) Metastatic potential correlates with size and depth.</li><ul> <li>(a) Size > 2 cm</li><li>(b) Depth of invasion (∼50% of bowel thickness)</li> </ul><li>(4) Foregut (e.g., stomach) and hindgut (e.g., rectum) carcinoid tumors</li><ul> <li>Invade but <i>rarely</i> metastasize</li> </ul><li>(5) Midgut carcinoid tumors (e.g., terminal ileum)</li><ul> <li>Invade and metastasize</li> </ul> </ul><li>Locations</li><ul> <li>(1) Vermiform appendix (<span>[[Fig. 17-36|Figure 17-36]]</span>)
<blockquote style="color: blue; ">Vermiform appendix: most common site for carcinoid tumor</blockquote></li><ul> <li>(a) Most common site (40%)</li><li>(b) Usually <2 cm, which is too small to metastasize to liver</li> </ul><li>(2) Small bowel (20%)</li><ul> <li>(a) Majority in terminal ileum</li><li>(b) Commonly metastasize to liver
<blockquote style="color: blue; ">Carcinoid tumor terminal ileum: metastasis to liver causes carcinoid syndrome</blockquote></li><li>(c) Tumor produces bioactive compounds (e.g., serotonin)</li><ul> <li>Compounds are delivered to the liver by the portal vein.</li> </ul><li>(d) Serotonin is metabolized to 5-hydroxyindoleacetic acid (5-HIAA).</li><ul> <li>5-HIAA is excreted in the urine.</li> </ul><li>(e) Serotonin is completely metabolized and does <i>not</i> enter the systemic circulation.</li><ul> <li>No signs or symptoms of carcinoid syndrome</li> </ul> </ul><li>(3) Esophagus, stomach, colon collectively (10%)</li> </ul><li>Bright yellow tumor
<blockquote style="color: blue; ">Carcinoid tumor: bright yellow</blockquote></li><li>Carcinoid syndrome
<blockquote style="color: blue; ">Carcinoid syndrome: liver metastasis is necessary</blockquote></li><ul> <li>(1) For gut origins (e.g., terminal ileum) of the carcinoid tumor, liver metastasis <i>must</i> occur to produce the syndrome.</li><ul> <li>(a) Serotonin is secreted by metastatic tumor nodules.</li><li>(b) Serotonin entering hepatic vein tributaries gains access to the systemic circulation.</li><li>(c) May occur without metastasis if located in the bronchus (rare)</li> </ul><li>(2) Clinical findings</li><ul> <li>(a) Due to serotonin and other bioactive compounds (e.g., histamine, bradykinin)</li><li>(b) Flushing of the skin (75-90%)</li><ul> <li>Due to vasodilation; may be triggered by emotion, alcohol, other foods</li> </ul><li>(c) Diarrhea (>70%)</li><ul> <li>Increased bowel motility
<blockquote style="color: blue; ">Carcinoid syndrome: flushing, diarrhea, wheezing; ↑ urine 5-HIAA</blockquote></li> </ul><li>(d) Intermittent wheezing and dyspnea (25%)</li><ul> <li>Due to bronchospasm</li> </ul><li>(e) Facial telangiectasia</li><li>(f) Tricuspid regurgitation and pulmonary stenosis</li><ul> <li>Serotonin increases collagen production in the valves.</li> </ul> </ul><li>(3) Diagnosis</li><ul> <li>(a) Increase in urine 5-HIAA</li><li>(b) CT scan of liver to detect metastasis</li><li>(c) Scanning techniques to detect primary location and metastasis</li> </ul><li>(4) Treatment</li><ul> <li>(a) Avoid alcohol</li><li>(b) Surgical resection of primary tumor</li><li>(c) Chemotherapy</li><li>(d) Somatostatin analogue</li><ul> <li>Effective in controlling diarrhea and flushing</li> </ul> </ul> </ul> </ol><li>Malignant lymphoma
<blockquote style="color: blue; ">Bowel primary lymphoma: usually in Peyer's patches in terminal ileum</blockquote></li><ol type="a"> <li>Usually occur in Peyer's patches of terminal ileum</li><li>Usually B-cell origin (e.g., Burkitt's lymphoma)</li> </ol> </ol> </ul>
</div></html>
<html><a name="HC017055"></a> <br><a name="P017067"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Sigmoid colon: most common site for gastrointestinal polyps, diverticula, cancer</blockquote>
<ol type="1"> <li>Non-neoplastic (hamartomatous) polyps</li><ol type="a"> <li>Hyperplastic polyp</li><ul> <li>(1) Most common type in adults</li><li>(2) Majority are in the sigmoid colon.</li><li>(3) <i>No</i> malignant potential or polyposis syndromes</li><li>(4) Histologically have a "sawtooth" appearance
<blockquote style="color: blue; ">Hyperplastic polyp: most common polyp in adults</blockquote></li> </ul><li>Juvenile (retention) polyps
<blockquote style="color: blue; ">Juvenile polyp: most common polyp in children</blockquote></li><ul> <li>(1) Most common polyp in children</li><li>(2) Located in the rectum</li><ul> <li>Sometimes prolapse out of the rectum and bleed</li> </ul><li>(3) Solitary polyp</li><ul> <li>Smooth surface with enlarged cystic spaces on cut section</li> </ul><li>(4) Juvenile polyposis
<blockquote style="color: blue; ">Hyperplastic and juvenile polyps: no malignant potential</blockquote></li><ul> <li>Autosomal dominant or nonhereditary</li> </ul><li>(5) Cronkhite-Canada syndrome</li><ul> <li>(a) Nonhereditary polyposis syndrome</li><li>(b) Polyps plus ectodermal abnormalities of the nails</li> </ul> </ul><li>Peutz-Jeghers polyposis (PJP)
<blockquote style="color: blue; ">PJP: predominance small intestine polyps</blockquote></li><ul> <li>(1) Autosomal dominant</li><li>(2) Hamartomatous polyps predominate in the small bowel</li><ul> <li>Less common in stomach and colon
<blockquote style="color: blue; ">PJP: ↑ risk colorectal, breast, gynecologic cancers</blockquote></li> </ul><li>(3) Clinical findings</li><ul> <li>(a) Mucosal pigmentation of buccal mucosa, lips (see <span>[[Fig. 17-4|Figure 17-4]]</span>)</li><li>(b) Increased risk (>50%) for colorectal, breast, gynecologic cancers</li><ul> <li>This is true even though the GI polyps are hamartomas.</li> </ul> </ul> </ul> </ol><li>Neoplastic polyps</li><ul> <li>Called adenomas</li><ol type="a"> <li>Premalignant dysplastic colonic polyps</li><ul> <li>(1) Increase with age</li><li>(2) Equal sex incidence</li> </ul><li>Tubular adenoma (adenomatous polyps)
<blockquote style="color: blue; ">Tubular adenoma: most common neoplastic polyp</blockquote></li><ul> <li>(1) Most common polyp (60% of polyps)</li><li>(2) Sigmoid colon is most common site.</li><li>(3) Stalked polyp</li><ul> <li>(a) Looks like a mushroom (<span>[[Fig. 17-37|Figure 17-37]]</span>)</li><li>(b) Sections show complex branching of glands (adenomatous change) (see <span>[[Fig. 8-1A|Figure 8-1]]</span>).</li> </ul> </ul><li>Tubulovillous adenoma (20-30% of polyps)</li><ul> <li>(1) Usually stalked polyp</li><li>(2) Adenomatous and villous change (similar to small bowel villi)</li> </ul><li>Villous adenoma (10% of polyps)</li><ul> <li>(1) Sessile polyp (no stalk) with primarily a villous component (<span>[[Fig. 17-38|Figure 17-38]]</span>)</li><li>(2) Rectosigmoid location</li><li>(3) Secrete protein and potassium-rich mucus</li><ul> <li>Can produce hypoalbuminemia and hypokalemia
<blockquote style="color: blue; ">Villous adenoma: may cause hypoproteinemia and hypokalemia</blockquote></li> </ul> </ul><li>Risk factors for malignancy in adenomas</li><ul> <li>(1) Adenoma > 2 cm (40% risk of malignancy)</li><li>(2) Multiple polyps</li><li>(3) Polyps with increased villous component
<blockquote style="color: blue; ">Villous adenoma: greatest risk for developing colon cancer</blockquote></li><ul> <li>Villous adenomas have a 30% to 40% risk for malignancy.</li> </ul> </ul><li>Familial polyposis (FP; <span>[[Fig. 17-39|Figure 17-39]]</span>)</li><ul> <li>(1) Autosomal dominant (AD)</li><ul> <li>(a) All patients develop tubular adenomas and cancer.
<blockquote style="color: blue; ">FP: AD; all patients develop colon cancer; complete penetrance</blockquote></li><li>(b) Polyps begin to develop between 10 and 20 years of age.</li> </ul><li>(2) Pathogenesis</li><ul> <li>Inactivation of adenomatous polyposis coli (APC) suppressor gene</li> </ul><li>(3) Clinical findings</li><ul> <li>(a) Malignant transformation usually occurs between 35 and 40 years of age.</li><ul> <li>Prophylactic colectomy is recommended.</li> </ul><li>(b) Associated with congenital hypertrophy of retinal pigment epithelium
<blockquote style="color: blue; ">Gardner's syndrome: AD; colon cancer; benign osteomas, desmoid tumors</blockquote></li> </ul><li>(4) Gardner's syndrome</li><ul> <li>(a) AD polyposis syndrome</li><li>(b) Additional findings include benign osteomas and desmoid tumors.</li> </ul><li>(5) Turcot's polyposis syndrome
<blockquote style="color: blue; ">Turcot's syndrome: AR; colon cancer; brain tumors</blockquote></li><ul> <li>(a) Autosomal recessive (AR) polyposis syndrome</li><li>(b) Additional finding of malignant brain tumors</li><ul> <li>Astrocytoma and medulloblastoma</li> </ul> </ul> </ul> </ol> </ul> </ol>
</div></html>
<html><a name="HC017056"></a> <br><a name="P017068"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Third most common cancer-related death in adults
<blockquote style="color: blue; ">Colon cancer: third most common cancer in men and women</blockquote></li><li>Third most common cancer in men and women</li><li>Incidence rates have been decreasing.</li><ul> <li>Increase in screening (fecal occult blood test, colonoscopy)</li> </ul><li>Peak incidence is in the seventh decade.
<blockquote style="color: blue; ">Whipple's disease: caused by <i>Tropheryma whippelii</i></blockquote></li><li>Rectal cancers</li><ul> <li>Approximately 50% are detected by digital rectal examination.</li> </ul><li>Colon cancers</li><ul> <li>Approximately 50% are detected by flexible sigmoidoscopy.</li> </ul><li>Risk factors for colon cancer
<blockquote style="color: blue; ">Colon cancer: third most common cancer killer in adults</blockquote></li><ul> <li>(1) Age > 50 years old</li><li>(2) Cigarette smoking</li><li>(3) Obesity, physical inactivity, heavy alcohol intake</li><li>(4) Hereditary polyposis syndromes (see later)</li><li>(5) Hereditary nonpolyposis colon cancer (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>)</li><li>(6) Family cancer syndrome (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>)</li><li>(7) First-degree relatives with colon cancer</li><li>(8) Inflammatory bowel disease</li><ul> <li>Ulcerative colitis > Crohn's disease</li> </ul><li>(9) Dietary factors</li><ul> <li>Low-fiber diet; increased saturated fats; reduced vegetable intake</li> </ul> </ul> </ol><li>Carcinogenesis of colon cancer</li><ol type="a"> <li>Adenoma-carcinoma sequence</li><ul> <li>(1) Sequential mutations of different genes</li><ul> <li><i>APC, RAS, TP53</i></li> </ul><li>(2) Accounts for 80% of sporadic colon cancers</li> </ul><li>Inactivation of DNA mismatch genes (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>)</li> </ol><li>Locations for colon cancer</li><ol type="a"> <li>Rectosigmoid (50% of cases)
<blockquote style="color: blue; ">Rectosigmoid: most common site for colon cancer</blockquote></li><li>Ascending colon (15% of cases)</li><li>Descending colon (15% of cases)</li><li>Transverse colon and cecum (each 10% of cases)</li> </ol><li>Screening tests for colon cancer</li><ol type="a"> <li>Fecal occult blood test (FOBT)</li><ul> <li>(1) <i>Not</i> very sensitive or specific for colon cancer</li><ul> <li>Does <i>not</i> distinguish hemoglobin from myoglobin</li> </ul><li>(2) Tests are based on the peroxidase activity of heme in Hb.</li><ul> <li>Myoglobin also has peroxidase activity.</li> </ul><li>(3) Peroxidase catalyzes the oxidation of a reagent (guaiac) by peroxide.
<blockquote style="color: blue; ">FOBT: most do not distinguish hemoglobin from myoglobin</blockquote></li><ul> <li>Reaction produces a color change.</li> </ul> </ul><li>Varying levels of sensitivity and specificity</li><ul> <li>(1) False positive results</li><ul> <li>(a) Myoglobin in meat</li><li>(b) Plant peroxidases (e.g., radishes)</li> </ul><li>(2) False negative results</li><li>(3) Newer tests detect hemoglobin</li> </ul><li>Colonoscopy (gold standard)</li><ul> <li>(1) Start at age 50 if no risk factors</li><li>(2) Every 3 to 5 years if history of polyp removal</li><li>(3) Begin at age 40 if first-degree relative has polyps or colorectal cancer</li> </ul><li>Barium enema</li> </ol><li>Clinical findings in colon cancer</li><ol type="a"> <li>Left-sided cancers
<blockquote style="color: blue; ">Left-sided colon cancer: tend to obstruct; small diameter</blockquote></li><ul> <li>(1) Tend to obstruct</li><ul> <li>(a) Bowel diameter is smaller than right colon.</li><li>(b) Lesions have an annular, "napkin-ring" appearance (<span>[[Figs. 17-40|Figure 17-40]]</span> and <span>[[17-41|Figure 17-41]]</span>).</li> </ul><li>(2) Change in bowel habits</li><ul> <li>(a) Constipation and diarrhea with or without bleeding</li><li>(b) Bright red blood coats the stool</li> </ul><li>(3) <i>Streptococcus bovis</i> endocarditis (refer to <span macro="tag [[10 Heart Disorders]] [[Chapter 10]]"></span>)</li> </ul><li>Right-sided cancers
<blockquote style="color: blue; ">Right-sided colon cancer: tend to bleed; large diameter; iron deficiency</blockquote></li><ul> <li>(1) Tend to bleed</li><ul> <li>(a) Bowel diameter is greater than left colon.</li><li>(b) Tumors are more polypoid in appearance.</li> </ul><li>(2) Blood is mixed in with stool.</li><li>(3) Iron deficiency is more likely than in left-sided cancer.</li> </ul> </ol><li>Sites of metastasis for colon cancer</li><ul> <li>Liver (most common), lungs, bone, and brain</li> </ul><li>Prevention
<blockquote style="color: blue; ">Prevention: aspirin, FOBT, dietary alterations, stop smoking</blockquote></li><ol type="a"> <li>Aspirin and other NSAIDs</li><ul> <li>Decreases incidence of colorectal adenomas</li> </ul><li>Annual fecal occult blood testing</li><li>Estrogens and progestins</li><ul> <li>May reduce colorectal cancer risk</li> </ul><li>Dietary alterations</li><ul> <li>(1) Decrease fat intake to 30% of total caloric intake</li><li>(2) Increase fiber</li><li>(3) Increase intake of fruits and vegetables</li> </ul><li>? Statins</li><ul> <li>May inhibit growth of colon cancer lines</li> </ul><li>Cessation of smoking</li> </ol><li>Treatment</li><ul> <li>Surgery, chemotherapy, targeted monoclonal antibody therapies</li> </ul><li>Prognosis</li><ol type="a"> <li>Five-year relative survival rate ∼65%</li><li>Serum carcinoembryonic antigen (CEA) is used to detect recurrences.</li> </ol> </ol>
</div></html>
<html><a name="HC017057"></a><span>[[Fig. 17-42|Figure 17-42]]</span> <br> <br><a name="P017069"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Occurs in 10% of the population
<blockquote style="color: blue; ">Acute appendicitis: most common abdominal surgical emergency</blockquote></li><li>Most common abdominal surgical emergency</li> </ol><li>Pathogenesis in children</li><ol type="a"> <li>Lymphoid hyperplasia (60% of cases) often secondary to a viral infection</li><li>Examples-adenovirus, measles virus infection or immunization</li> </ol><li>Pathogenesis in adults
<blockquote style="color: blue; ">Acute diverticulitis and appendicitis have the same pathogenesis.</blockquote></li><ol type="a"> <li>Fecalith obstructs the proximal lumen</li><ul> <li>Increased intraluminal pressure causes mucosal injury and bacterial invasion.</li> </ul><li>Other causes</li><ul> <li>Seeds (sunflower, persimmons), pinworm infection</li> </ul><li>Primary pathogens are <i>Escherichia coli</i> (most common) and <i>Bacteroides fragilis.</i></li> </ol><li>Clinical findings in sequence</li><ol type="a"> <li>Initial colicky periumbilical pain (50%)
<blockquote style="color: blue; ">Pain in acute appendicitis: initially periumbilical and then shifts to RLQ</blockquote></li><ul> <li>(1) Irritation of unmyelinated afferent C fibers on visceral peritoneal surface</li><li>(2) Refer pain to the midline</li> </ul><li>Fever
<blockquote style="color: blue; ">C fibers: refer to midline</blockquote></li><ul> <li>Very important sign for identifying appendicitis in children with abdominal pain</li> </ul><li>Nausea, vomiting, and fever
<blockquote style="color: blue; ">Acute appendicitis: pain precedes nausea and vomiting</blockquote></li><ul> <li>Pain <i>precedes</i> nausea and vomiting</li> </ul><li>Cutaneous hyperesthesia at level of T12</li><li>Pain shifts to right lower quadrant (RLQ) in 12 to 18 hours.</li><ul> <li>(1) Irritation of Aδ fibers on parietal peritoneum
<blockquote style="color: blue; ">Aδ fibers: localize pain</blockquote></li><ul> <li>Localizes pain to the exact location</li> </ul><li>(2) Rebound tenderness at McBurney's point (Blumberg's sign)</li><li>(3) Pain with right thigh extension (psoas sign)</li><li>(4) RLQ pain with palpation of left lower quadrant (Rovsing's sign)</li> </ul><li>Signs of a lower urinary tract infection may occur.</li><ul> <li>(1) Increased frequency</li><li>(2) Dysuria</li> </ul><li>Laboratory findings</li><ul> <li>(1) Neutrophilic leukocytosis with left shift (90%)</li><li>(2) Abnormal urinalysis:</li><ul> <li>Increased protein, hematuria, pyuria</li> </ul> </ul> </ol><li>Retrocecal appendicitis
<blockquote style="color: blue; ">Retrocecal appendicitis: sentinel loop</blockquote></li><ol type="a"> <li>Radiograph shows a sentinel loop in the RLQ</li><li>Localized ileus (lack of motility) from subjacent appendicitis</li> </ol><li>Complications</li><ol type="a"> <li>Periappendiceal abscess with or without perforation
<blockquote style="color: blue; ">Acute appendicitis: periappendiceal abscess most common complication</blockquote></li><ul> <li>(1) Most common complication</li><li>(2) May develop subphrenic abscess</li><ul> <li>Usually due to <i>Bacteroides fragilis</i></li> </ul> </ul><li>Pyelophlebitis
<blockquote style="color: blue; ">Pyelophlebitis: inflammation of portal vein</blockquote></li><ul> <li>(1) Infection of the portal vein</li><li>(2) Danger of portal vein thrombosis</li><li>(3) Radiograph shows gas in the portal vein.</li> </ul><li>Subphrenic abscess
<blockquote style="color: blue; ">Subphrenic abscess: persistent fever postoperative</blockquote></li><ul> <li>(1) Persistent fever postoperative</li><li>(2) Diaphragm fixed on the right; right-sided pleural effusion</li><li>(3) Tenderness over lateral seventh and eighth ribs</li><li>(4) Diagnosis</li><ul> <li>Ultrasound, CT scan, gallium scan</li> </ul><li>(5) Treatment</li><ul> <li>Extraperitoneal drainage and antibiotics</li> </ul> </ul> </ol><li>Diagnosis of acute appendicitis</li><ol type="a"> <li>Clinical examination</li><li>Spiral CT RLQ after Gastrografin enema
<blockquote style="color: blue; ">Acute appendicitis diagnosis: spiral CT or plain CT with rectal contrast</blockquote></li><ul> <li>Sensitivity 90% and specificity 94%</li> </ul><li>Plain CT scan with rectal contrast agent</li><li>Ultrasonography</li><ul> <li>Sensitivity 75% and specificity 90%</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Appendectomy</li><li>Cefoxitin</li><ul> <li>Given prophylactically perioperatively if perforation suspected</li> </ul> </ol> </ol>
</div><a name="PB017005"></a><div class="BB" style="color: rgb(47, 79, 79); ">Many disorders mimic appendicitis. These disorders include viral gastroenteritis, ruptured follicular cyst, ruptured ectopic pregnancy, mesenteric lymphadenitis, and Meckel's diverticulitis.</div></html>
![[17.IV.A.Signs and symptoms of small bowel disease]]
<<tiddler [[17.IV.A.Signs and symptoms of small bowel disease]]>>
![[17.IV.B.Signs and symptoms of large bowel disease]]
<<tiddler [[17.IV.B.Signs and symptoms of large bowel disease]]>>
![[17.IV.C.Diarrheal diseases (excluding malabsorption)]]
<<tiddler [[17.IV.C.Diarrheal diseases (excluding malabsorption)]]>>
![[17.IV.D.Malabsorption]]
<<tiddler [[17.IV.D.Malabsorption]]>>
![[17.IV.E.Bowel obstruction]]
<<tiddler [[17.IV.E.Bowel obstruction]]>>
![[17.IV.F.Hernias]]
<<tiddler [[17.IV.F.Hernias]]>>
![[17.IV.G.Vascular disorders]]
<<tiddler [[17.IV.G.Vascular disorders]]>>
![[17.IV.H.Small bowel diverticula]]
<<tiddler [[17.IV.H.Small bowel diverticula]]>>
![[17.IV.I.Sigmoid colon diverticular disease]]
<<tiddler [[17.IV.I.Sigmoid colon diverticular disease]]>>
![[17.IV.J.Inflammatory bowel disease]]
<<tiddler [[17.IV.J.Inflammatory bowel disease]]>>
![[17.IV.K.Irritable bowel syndrome (IBS)]]
<<tiddler [[17.IV.K.Irritable bowel syndrome (IBS)]]>>
![[17.IV.L.Small bowel malignancy]]
<<tiddler [[17.IV.L.Small bowel malignancy]]>>
![[17.IV.M.Small and large bowel polyps]]
<<tiddler [[17.IV.M.Small and large bowel polyps]]>>
![[17.IV.N.Colon cancer]]
<<tiddler [[17.IV.N.Colon cancer]]>>
![[17.IV.O.Acute appendicitis (Fig. 17-42)]]
<<tiddler [[17.IV.O.Acute appendicitis (Fig. 17-42)]]>>
<html><a name="HC017059"></a> <br><a name="P017095"></a><div class="PA" style="color: black; "><ol type="1"> <li>Bleeding</li><ol type="a"> <li>Internal hemorrhoids (painless)
<blockquote style="color: blue; ">Anorectal bleeding: internal hemorrhoids most common cause</blockquote></li><li>Anorectal cancer</li><li>Infection</li><li>Fissure</li> </ol><li>Pain</li><ol type="a"> <li>Anal fissure</li><li>Thrombosed external hemorrhoids</li> </ol><li>Pruritus (e.g., pinworms)</li><li>Anal fistula (e.g., Crohn's disease)</li> </ol>
</div></html>
![[17.V.A.Signs and symptoms of anorectal disease]]
<<tiddler [[17.V.A.Signs and symptoms of anorectal disease]]>>
![[17.V.B.Disorders]]
<<tiddler [[17.V.B.Disorders]]>>
<html><a name="HC017060"></a> <br><a name="PB017006"></a><div class="BB" style="color: rgb(47, 79, 79); ">In an adult, never assume that blood coating stool is always due to an internal hemorrhoid. Other causes include colorectal and anal cancer; therefore, further investigation is necessary.</div><a name="P017096"></a><div class="PA" style="color: black; "><ol type="1"> <li>Internal hemorrhoids</li><ol type="a"> <li>Dilated superior hemorrhoidal veins in mucosa and submucosa</li><ul> <li>Located above the pectinate line (superior plexus)</li> </ul><li>Causes
<blockquote style="color: blue; ">Internal hemorrhoids: straining at stool; painless bleeding</blockquote></li><ul> <li>(1) Straining at stool (most common)</li><ul> <li>Often associated with constipation, low-fiber diet</li> </ul><li>(2) Pregnancy</li><li>(3) Obesity</li><li>(4) Anal intercourse</li><li>(5) Portal hypertension
<blockquote style="color: blue; ">Internal hemorrhoids: commonly prolapse out of the rectum</blockquote></li> </ul><li>Clinical findings</li><ul> <li>(1) Often prolapse out of the rectum (<span>[[Fig. 17-43|Figure 17-43]]</span>)</li><li>(2) Commonly pass bright red blood with stool</li><ul> <li>(a) Blood coats the stool.</li><li>(b) Painless bleeding</li> </ul><li>(3) Anal pruritus and soiling of underwear
<blockquote style="color: blue; ">Internal hemorrhoids: anal pruritus, soiling of underwear</blockquote></li> </ul><li>Treatment</li><ul> <li>(1) Nonpharmacologic</li><ul> <li>High-fiber diet; warm soaks/sitz baths; avoid prolonged sitting or stooling</li> </ul><li>(2) Pharmacologic</li><ul> <li>(a) Topical hydrocortisone</li><li>(b) Stool softeners</li> </ul> </ul><li>Surgical</li><ul> <li>(1) Rubber-band ligation (best overall), sclerotherapy, infrared photocoagulation</li><li>(2) Hemorrhoidectomy</li><ul> <li>Overall most effective, but most painful</li> </ul> </ul> </ol><li>External hemorrhoids
<blockquote style="color: blue; ">External hemorrhoids: painful thrombosis inferior hemorrhoidal veins</blockquote></li><ol type="a"> <li>Dilated inferior hemorrhoidal veins</li><ul> <li>Located below the pectinate line (inferior plexus)</li> </ul><li>Painful thrombosis</li><li>Causes and treatment</li><ul> <li>See preceding internal hemorrhoid discussion</li> </ul> </ol><li>Rectal prolapse</li><ol type="a"> <li>Intussusception of the rectum through the anus</li><ul> <li>Due to weak rectal support mechanisms</li> </ul><li>Causes in children < 2 years old
<blockquote style="color: blue; ">Rectal prolapse in children < 2 years old: whooping cough, trichuriasis, cystic fibrosis</blockquote></li><ul> <li>(1) Whooping cough</li><li>(2) Trichuriasis</li><li>(3) Common sign of cystic fibrosis</li> </ul><li>Common in the elderly
<blockquote style="color: blue; ">Rectal prolapse in elderly: straining at stool</blockquote></li><ul> <li>Due to straining at stool</li> </ul><li>May occur with heavy squats in power lifters</li> </ol><li>Pilonidal sinus and abscess
<blockquote style="color: blue; ">Pilonidal sinus/abscess: painful mass in deep gluteal fold</blockquote></li><ol type="a"> <li>Excess hair in a deep gluteal fold</li><ul> <li>Becomes traumatically buried into a sinus</li> </ul><li>Painful sacrococcygeal mass with purulent drainage</li><li>Treatment</li><ul> <li>(1) Incision and drainage first episode</li><li>(2) Chronic disease</li><ul> <li>Marsupialization-wide excision and wound left open</li> </ul> </ul> </ol><li>Pruritus ani</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) More common in males than females</li><li>(2) Occurs in 1% to 5% of population
<blockquote style="color: blue; ">Pruritus ani: internal hemorrhoids, diabetes, pinworm</blockquote></li> </ul><li>Numerous causes</li><ul> <li>(1) Anorectal diseases</li><ul> <li>Internal hemorrhoids (common), fissures, anal incontinence, diarrhea, cancer</li> </ul><li>(2) Infections</li><ul> <li>Pinworm, <i>Candida</i>, venereal diseases</li> </ul><li>(3) Local irritants</li><ul> <li>Soap, underwear, obesity, coffee, beer, acidic foods</li> </ul><li>(4) Dermatologic disease</li><ul> <li>Psoriasis, atopic dermatitis</li> </ul><li>(5) Diabetes mellitus</li> </ul> </ol><li>Anorectal fistulas</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Common in all ages</li><li>(2) Associated with constipation</li><li>(3) Pediatric population</li><ul> <li>(a) More common in infants</li><li>(b) Boys > girls</li> </ul><li>(4) Etiology</li><ul> <li>(a) Nonspecific cryptoglandular infection most common
<blockquote style="color: blue; ">Anorectal fistula: Crohn's disease, cryptoglandular infection</blockquote></li><li>(b) Inflammatory bowel disease</li><ul> <li>Crohn's disease > ulcerative colitis</li> </ul><li>(c) Trauma</li><ul> <li>Episiotomy, prostatectomy, anal intercourse</li> </ul><li>(d) Malignancy</li><ul> <li>Anal carcinoma, treatment for anal carcinoma</li> </ul> </ul> </ul><li>Treatment is surgery.</li> </ol><li>Anal fissures</li><ol type="a"> <li>Epidemiology</li><ul> <li>Accounts for >10% of anal complaints</li> </ul><li>Pathophysiology</li><ul> <li>(1) Firm bowel movements</li><ul> <li>Once formed, perpetuated by bowel movements</li> </ul><li>(2) Associated and perpetuated by spasm of the internal sphincter</li> </ul><li>Clinical
<blockquote style="color: blue; ">Anal fissure: most posteriorly located; anal tag marks location</blockquote></li><ul> <li>(1) Posterior (90%) fissure and/or ulcer between anal verge and dentate line</li><ul> <li>Consider Crohn's disease if not in this location</li> </ul><li>(2) Anal tag at anal verge marks its location.</li><li>(3) Prominent proximal papilla</li> </ul><li>Treatment</li><ul> <li>(1) Nitroglycerin ointment</li><li>(2) Botulinum toxin injection of anal sphincter</li><li>(3) Surgery</li> </ul> </ol><li>Anal carcinoma</li><ol type="a"> <li>Basaloid (epidermoid or cloacogenic) carcinoma</li><ul> <li>(1) Most common type
<blockquote style="color: blue; ">Anal carcinoma: basaloid carcinoma most common</blockquote></li><li>(2) Located in the transitional zone above the dentate line</li><li>(3) Female dominant</li><li>(4) Treatment is surgery.</li> </ul><li>Squamous cell carcinoma
<blockquote style="color: blue; ">Anal carcinoma: squamous cancer has HPV 16 and 18 relationship</blockquote></li><ul> <li>(1) Located in the anal canal</li><li>(2) Majority occur in men who have sex with men.</li><ul> <li>HPV 16 and 18 association</li> </ul><li>(3) Treatment is surgery.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC018002"></a> <br><a name="P018001"></a><div class="PA" style="color: black; "><ol type="1"> <li>Bilirubin metabolism (<span>[[Fig. 18-1|Figure 18-1]]</span>)</li><ol type="a"> <li>Unconjugated bilirubin (UCB)
<blockquote style="color: blue; ">UCB: end-product of heme degradation in splenic macrophages</blockquote></li><ul> <li>(1) Senescent RBCs are phagocytosed by splenic macrophages.</li><li>(2) UCB is the end-product of heme degradation.</li><ul> <li>UCB is lipid-soluble (indirect bilirubin).</li> </ul> </ul><li>UCB combines with albumin in the blood.
<blockquote style="color: blue; ">UCB: lipid soluble</blockquote></li><ul> <li>(1) UCB is taken up by hepatocytes.</li><li>(2) UCB is conjugated to glucuronic acid to produce conjugated bilirubin (CB).</li><ul> <li>CB is water soluble (direct bilirubin).</li> </ul> </ul><li>CB is secreted into the intrahepatic bile ducts.
<blockquote style="color: blue; ">CB: glucuronic acid makes bilirubin water soluble</blockquote></li><ul> <li>(1) Temporarily stored in the gallbladder</li><li>(2) Enters the duodenum via the common bile duct</li> </ul><li>Intestinal bacteria convert CB to urobilinogen (UBG).
<blockquote style="color: blue; ">Intestinal bacteria: convert CB → UBG</blockquote></li><ul> <li>(1) UBG is spontaneously oxidized to urobilin.</li><li>(2) Urobilin produces the brown color of stool.
<blockquote style="color: blue; ">UBG: 20% recycled to liver and kidneys</blockquote></li> </ul><li>Approximately 20% of UBG is recycled to the liver (90%) and kidneys (10%).</li><ul> <li>Color of urine is due to urobilin.</li> </ul> </ol><li>Jaundice
<blockquote style="color: blue; ">Urobilin: color of stool and urine</blockquote></li><ol type="a"> <li>Jaundice is due to an increase in UCB and/or CB.</li><ul> <li>(1) Jaundice is first noticed in the sclera (<span>[[Fig. 18-2|Figure 18-2]]</span>).</li><li>(2) Sclera has a high affinity for bilirubin.
<blockquote style="color: blue; ">Viral hepatitis: most common cause of jaundice</blockquote></li> </ul><li>Classification of causes of jaundice is based on the percentage of CB (<span>[[Table 18-1|Table 18-1. CAUSES OF JAUNDICE]]</span>).</li><ul> <li>Percent CB = CB/total bilirubin</li> </ul><li>Common causes of jaundice (<span>[[Box 18-1|BOX 18-1 COMMON CAUSES OF JAUNDICE]]</span>)
<blockquote style="color: blue; ">Gilbert's disease: 2nd most common cause of jaundice; fasting unconjugated hyperbilirubinemia</blockquote></li> </ol> </ol>
</div></html>
<html><a name="HC018003"></a><span>[[Table 18-2|Table 18-2. LIVER FUNCTION TESTS]]</span> <br> <br> </html>
<html><a name="HC018004"></a><span>[[Table 18-3|Table 18-3. SUMMARY OF LABORATORY FINDINGS IN SELECTED LIVER DISORDERS]]</span> <br> <br> </html>
![[18.I.A.Bilirubin metabolism and jaundice]]
<<tiddler [[18.I.A.Bilirubin metabolism and jaundice]]>>
![[18.I.B.Summary of liver function tests (Table 18-2)]]
<<tiddler [[18.I.B.Summary of liver function tests (Table 18-2)]]>>
![[18.I.C.Summary of laboratory findings in selective liver disorders (Table 18-3)]]
<<tiddler [[18.I.C.Summary of laboratory findings in selective liver disorders (Table 18-3)]]>>
<html><a name="HC018006"></a> <br><a name="P018002"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Phases acute hepatitis: prodrome, jaundice, recovery</blockquote>
<ol type="1"> <li>Prodrome</li><ol type="a"> <li>Fever</li><li>Painful hepatomegaly; distaste for alcohol/cigarettes</li><li>Serum transaminases increase steadily.
<blockquote style="color: blue; ">Transaminases: peak before jaundice</blockquote></li><ul> <li>Peak just <i>before</i> jaundice occurs</li> </ul><li>Atypical lymphocytosis</li> </ol><li>Jaundice</li><ol type="a"> <li>Variable finding depending on the type of hepatitis</li><li>Increased urine bilirubin and urine UBG</li> </ol><li>Recovery</li><ul> <li>Jaundice resolves.</li> </ul> </ol>
</div></html>
<html><a name="HC018007"></a> <br><a name="P018003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Lymphocytic infiltrate with destruction of hepatocytes (see <span>[[Fig. 2-9|Figure 2-9]]</span>)</li><ul> <li>Apoptosis of hepatocytes (Councilman bodies; see <span>[[Fig. 1-12|Figure 1-12]]</span>)</li> </ul><li>Persistent inflammation and fibrosis is an unfavorable sign.
<blockquote style="color: blue; ">Hepatitis A: most common viral cause of jaundice</blockquote></li><ul> <li>Sign of chronic hepatitis progressing to postnecrotic cirrhosis</li> </ul> </ol>
</div></html>
<html><a name="HC018008"></a><span>[[Table 18-4|Table 18-4. VIRAL HEPATITIS: TRANSMISSION AND CLINICAL FINDINGS]]</span> <br> <br> </html>
<html><a name="HC018009"></a> <br><a name="P018004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hepatitis A virus (HAV)
<blockquote style="color: blue; ">HAV: anti-HAV-IgM indicates infection; anti-HAV-IgG indicates recovery/vaccination</blockquote></li><ol type="a"> <li>Anti-HAV-IgM indicates active infection.</li><li>Anti-HAV-IgG indicates recovery from infection or vaccination.
<blockquote style="color: blue; ">Extravascular hemolysis: ↑↑ UBG, no UB</blockquote></li><ul> <li>Protective antibody</li> </ul> </ol><li>Hepatitis B virus (HBV) (<span>[[Fig. 18-3|Figure 18-3]]</span> and <span>[[Table 18-5|Table 18-5. SEROLOGIC STUDIES IN HEPATITIS B VIRUS (HBV)]]</span>)</li><ol type="a"> <li>Hepatitis B surface antigen (HBsAg)</li><ul> <li>(1) Appears within 2 to 8 weeks after exposure</li><ul> <li>First marker of infection
<blockquote style="color: blue; ">HBsAg: first antigen to arrive and last one to leave with recovery</blockquote></li> </ul><li>(2) Persists up to 4 months in acute hepatitis</li><ul> <li>HBsAg longer than 6 months defines chronic HBV.</li> </ul> </ul><li>Hepatitis B e antigen (HBeAg) and HBV-DNA
<blockquote style="color: blue; ">HBeAg and HBV-DNA: infective particles</blockquote></li><ul> <li>(1) Infective particles</li><li>(2) Appear <i>after</i> HBsAg and disappear <i>before</i> HBsAg</li> </ul><li>Anti-HBV core antibody IgM (anti-HBc-IgM)</li><ul> <li>(1) Nonprotective antibody</li><ul> <li>Remains positive in acute infections
<blockquote style="color: blue; ">Anti-HBc-IgM: only marker present during window phase</blockquote></li> </ul><li>(2) Persists during "window phase" or "serologic gap"</li><ul> <li>HBsAg, HBV DNA, and HBeAg are absent.</li> </ul><li>(3) Converts entirely to anti-HBc-IgG by 6 months
<blockquote style="color: blue; ">Anti-HBc-IgG: present after 6 months</blockquote></li> </ul><li>Anti-HBV surface antibody (anti-HBs)</li><ul> <li>(1) Protective antibody</li><li>(2) Marker of immunization after HBV vaccination
<blockquote style="color: blue; ">Anti-HBs: protective antibody; immunization or recovery from past infection</blockquote></li> </ul><li>Chronic HBV</li><ul> <li>(1) Persistence of HBsAg longer than 6 months</li><ul> <li>Anti-HBc-IgM converts to anti-HBc-IgG.
<blockquote style="color: blue; ">HBsAg > 6 months defines chronic HBV</blockquote></li> </ul><li>(2) "Healthy" chronic carrier</li><ul> <li>(a) Presence of HBsAg and anti-HBc-IgG</li><li>(b) Absence of DNA and e antigen
<blockquote style="color: blue; ">"Healthy" carrier: HBsAg, anti-HBc-IgG</blockquote></li><li>(c) Still contagious but at a much lower risk</li> </ul><li>(3) Infective chronic carrier
<blockquote style="color: blue; ">Infective carrier: HBsAg, HBeAg, HBV-DNA, anti-HBc-IgG</blockquote></li><ul> <li>(a) Presence of HBsAg, anti-HBc-IgG, and infective particles (DNA and e antigen)</li><li>(b) Increased risk for postnecrotic cirrhosis and hepatocellular carcinoma</li> </ul> </ul> </ol><li>Hepatitis C virus (HCV)</li><ol type="a"> <li>Screen with enzyme immunoassay (EIA)</li><ul> <li>(1) Presence of anti-HCV-IgG indicates active infection or recovery.</li><ul> <li>Sensitivity > 97%</li> </ul><li>(2) It does <i>not</i> differentiate among acute, chronic, or resolved infection.</li><li>(3) It is <i>not</i> a protective antibody.</li> </ul><li>Confirmatory tests
<blockquote style="color: blue; ">HCV testing: screen with EIA; confirm with RIBA and HCV RNA</blockquote></li><ul> <li>(1) Recombinant immunoblot assay (RIBA)</li><ul> <li>(a) Supplemental test if EIA is positive</li><li>(b) More specific but less sensitive than EIA</li> </ul><li>(2) HCV RNA using polymerase chain reaction
<blockquote style="color: blue; ">HCV RNA: gold standard test</blockquote></li><ul> <li>(a) Gold standard test for diagnosing HCV</li><li>(b) Detects virus as early as 1 to 2 weeks after infection</li><li>(c) Used to monitor patients on antiviral therapy</li> </ul><li>(3) Positive RIBA and HCV RNA indicate active infection.</li><li>(4) Positive RIBA and negative HCV RNA indicate recent recovery.</li> </ul> </ol><li>Hepatitis D virus (HDV)</li><ol type="a"> <li>Presence of anti-HDV-IgM or IgG indicates active infection.</li><li>IgG is <i>not</i> a protective antibody.
<blockquote style="color: blue; ">HCV, HDV: no protective antibodies</blockquote></li> </ol><li>Hepatitis E virus (HEV)</li><ol type="a"> <li>Presence of anti-HEV-IgM indicates active infection.</li><li>Anti-HEV-IgG indicates recovery (protective antibody).</li> </ol> </ol>
</div></html>
<html><a name="HC018010"></a><span>[[Box 18-1C|BOX 18-1 COMMON CAUSES OF JAUNDICE]]</span> <br> <br><a name="P018005"></a><div class="PA" style="color: black; "><ol type="1"> <li>CB 20% to 50% (mixed hyperbilirubinemia)</li><ol type="a"> <li>Decreased uptake/conjugation of UCB</li><li>CB gains access to blood via damaged bile ductules.</li> </ol><li>Increased urine UBG and urine bilirubin
<blockquote style="color: blue; ">Viral hepatitis: urine UBG ++, urine bilirubin ++</blockquote></li><ol type="a"> <li>CB is water soluble and is filtered in the kidneys.</li><li>UBG recycled back to inflamed liver is redirected to the kidneys.</li> </ol><li>Increased serum transaminases</li><ol type="a"> <li>Serum ALT is greater than AST.
<blockquote style="color: blue; ">Serum ALT: last enzyme to return to normal</blockquote></li><li>Serum ALT is the last liver enzyme to return to normal.</li> </ol> </ol>
</div><a name="B018001"></a><div class="BT">BOX 18-1 COMMON CAUSES OF JAUNDICE</div><a name="PB018001"></a><div class="BB" style="color: rgb(47, 79, 79); "><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-018-g001.jpg" id=""><br>In this discussion, the symbol (+) is used to indicate degrees of magnitude. <b>Normal bilirubin metabolism</b> (<b>A</b>) shows liver uptake of lipid-soluble unconjugated bilirubin (UCB) and its conjugation with glucuronic acid to produce water-soluble conjugated bilirubin (CB). CB is secreted into the common bile duct (CBD) and is emptied into the bowel. Intestinal bacteria convert CB to urobilinogen (UBG), which spontaneously oxidizes to the pigment urobilin. Urobilin is responsible for the color of stool. A small percentage of UBG is reabsorbed into the blood. Most of it enters the liver (<i>larger arrow</i>) and a small percentage (<i>smaller arrow</i>) enters the urine (UBG). Urobilin is responsible for the color of urine. All of the normal bilirubin in blood is UCB (CB% < 20%) primarily derived from macrophage destruction of senescent RBCs. UCB does <i>not</i> enter urine, because it is attached to albumin in the blood and is lipid, <i>not</i> water, soluble. CB is <i>never</i> a normal finding in urine because it does <i>not</i> have contact with blood in its metabolism.</div><a name="PB018002"></a><div class="BB" style="color: rgb(47, 79, 79); ">In <b>extravascular hemolysis</b> (<b>B</b>) (e.g., hereditary spherocytosis), there is increased macrophage production of UCB causing an increase in serum UCB (++) (CB% < 20%). There is a corresponding increase in uptake and conjugation of UCB, conjugation to CB (++), and conversion of CB in the bowel to UBG (++). This causes darkening of the stool. There is a greater percentage of UBG recycled back to the liver (<i>wider arrow</i>) and urine (<i>wider arrow</i>). The increase in urine UBG (++), darkens the color of urine. Because RBCs contain the enzyme aspartate aminotransferase (AST), hemolysis of RBCs causes an increase in serum AST. Alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) levels are normal.</div><a name="PB018003"></a><div class="BB" style="color: rgb(47, 79, 79); ">In <b>viral hepatitis</b> (<b>C</b>), there is generalized liver dysfunction involving uptake and conjugation of UCB, secretion of CB into bile ducts, and recycling of UBG. Serum UCB is increased (++) owing to a decrease in uptake and conjugation. Serum and urine CB are increased (++) because of liver cell necrosis and disruption of bile ductules between hepatocytes. Urine UBG is increased (++) because UBG is redirected from the liver (<i>smaller arrow</i>) to the kidneys (<i>larger arrow</i>). Because there is an increase in serum UCB and CB, there is a mixed hyperbilirubinemia with a CB% of 20% to 50%. In viral hepatitis, aLT is higher (+++) than AST (++) and there is a slight increase in ALP and GGT (+). In alcoholic hepatitis, AST is greater than ALT, because alcohol damages mitochondria, which is where AST is normally located.</div><a name="PB018004"></a><div class="BB" style="color: rgb(47, 79, 79); ">In <b>obstructive liver disease</b> (<b>D</b>), an increase in serum and urine CB (++) is due to obstruction of intrahepatic or extrahepatic bile flow (stone in the CBD in this case). This causes increased pressure in the intrahepatic bile ductules leading to rupture and egress of CB into sinusoidal blood. There is absence of UBG in the stool (light-colored) and urine. CB% > 50% and there is a marked increase in serum ALP and GGT (+++) and only a slight increase in serum AST and ALT (+).</div></html>
![[18.II.A.Phases of acute viral hepatitis]]
<<tiddler [[18.II.A.Phases of acute viral hepatitis]]>>
![[18.II.B.Microscopic findings in acute viral hepatitis]]
<<tiddler [[18.II.B.Microscopic findings in acute viral hepatitis]]>>
![[18.II.C.Epidemiology of viral hepatitis (Table 18-4)]]
<<tiddler [[18.II.C.Epidemiology of viral hepatitis (Table 18-4)]]>>
![[18.II.D.Serologic studies in viral hepatitis]]
<<tiddler [[18.II.D.Serologic studies in viral hepatitis]]>>
![[18.II.E.Other laboratory test findings (see Box 18-1C)]]
<<tiddler [[18.II.E.Other laboratory test findings (see Box 18-1C)]]>>
<html><a name="HC018012"></a><span>[[Fig. 18-4|Figure 18-4]]</span> <br><span>[[Table 18-6|Table 18-6. INFECTIOUS DISEASES OF THE LIVER]]</span> <br> <br> </html>
<html><a name="HC018013"></a> <br><a name="P018009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Two types</li><ul> <li>(1) Type 1 is the predominant form in the United States and worldwide (80%).
<blockquote style="color: blue; ">Autoimmune hepatitis: type 1 most common in the United States</blockquote></li><li>(2) Type 2 is uncommon in the United States (not discussed).</li> </ul><li>Occurs most often in young women</li><li>Range of presentations</li><ul> <li>(1) Symptomatic with increased transaminases</li><li>(2) Fulminant hepatitis</li><li>(3) Cirrhosis</li> </ul><li>Human leukocyte antigen (HLA) DR3 and DR4 association</li><li>Other autoimmune associations</li><ul> <li>Examples-Hashimoto's thyroiditis, Graves' disease</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Fever</li><li>Jaundice</li><li>Hepatosplenomegaly</li> </ol><li>Laboratory findings for type 1
<blockquote style="color: blue; ">Autoimmune hepatitis: + serum ANA, + anti-smooth muscle antibodies</blockquote></li><ol type="a"> <li>Positive serum antinuclear antibody (ANA) test (>60%)</li><li>Anti-smooth muscle antibodies (>85%)</li><li>Increased serum transaminases</li><li>Decreased serum albumin in severe disease</li><li>Prolonged prothrombin time in severe disease</li> </ol><li>Treatment</li><ol type="a"> <li>Initial treatment with corticosteroids + azathioprine</li><li>Liver transplantation if resistant to therapy</li> </ol> </ol>
</div></html>
<html><a name="HC018014"></a> <br><a name="P018010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Idiopathic</li><li>Associated with congenital infections</li><ul> <li>Example-cytomegalovirus</li> </ul><li>Associated with inborn errors of metabolism
<blockquote style="color: blue; ">Neonatal hepatitis: multifactorial; biopsy shows multinucleated giant cells</blockquote></li><ul> <li>Example-α<sub>1</sub>-antitrypsin deficiency</li> </ul> </ol><li>Biopsy shows multinucleated giant cells.</li><ul> <li>"Giant cell" hepatitis</li> </ul> </ol>
</div></html>
<html><a name="HC018015"></a> <br><a name="P018011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Postinfectious triad:</li><ul> <li>(1) Encephalopathy</li><li>(2) Microvesicular fatty change</li><li>(3) Transaminase elevation</li> </ul><li>Uncommon since the role of aspirin was elucidated</li><li>Usually develops in children < 4 years old
<blockquote style="color: blue; ">Reye syndrome: association with aspirin and infection (chickenpox, influenza)</blockquote></li><ul> <li>Often follows a chickenpox or influenza infection</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Mitochondrial damage (? virus, salicylates)</li><li>Disruption of the urea cycle</li><ul> <li>Increase in serum ammonia</li> </ul><li>Defective β-oxidation of fatty acids</li> </ol><li>Microvesicular fatty change (? salicylate effect)</li><ol type="a"> <li>Small cytoplasmic globules <i>without</i> nuclear displacement</li><li>No inflammatory infiltrate</li> </ol><li>Clinical findings
<blockquote style="color: blue; ">Reye syndrome: encephalopathy, fatty change in liver, ↑ transaminases</blockquote></li><ol type="a"> <li>Initially afebrile, quiet, lethargic, sleepy, and vomiting</li><ul> <li>Hepatomegaly and liver dysfunction present</li> </ul><li>Encephalopathy findings in progression</li><ul> <li>Signs and symptoms related to cerebral edema and increasing pressure
<blockquote style="color: blue; ">Reye syndrome: sleepy but respond → stuporous → obtundation → coma</blockquote></li> </ul><ul> <li>(1) Sleepy but respond; vomiting</li><li>(2) Stuporous, seizures, decorticate rigidity, intact papillary reflexes</li><li>(3) Deepening coma, decerebrate rigidity, fixed pupils</li><li>(4) Coma, loss of deep tendon reflexes, fixed dilated pupils, flaccidity/decerebrate</li><li>(5) Death</li> </ul> </ol><li>Laboratory findings
<blockquote style="color: blue; ">Reye syndrome: ↑ transaminasemia, bilirubin, PT, ammonia; ↓glucose</blockquote></li><ol type="a"> <li>Transaminasemia</li><li>Normal to slight increase in total bilirubin</li><li>Increased serum ammonia and prothrombin time (PT)</li><ul> <li>Levels predict degree of severity</li> </ul><li>Hypoglycemia</li><li>Cerebrospinal fluid usually normal</li> </ol><li>Treatment</li><ol type="a"> <li>Supportive</li><li>Mannitol, glycerol, or hyperventilation to reduce cerebral edema</li> </ol><li>Approximately 25% to 50% mortality rate</li> </ol>
</div></html>
<html><a name="HC018016"></a> <br><a name="P018012"></a><div class="PA" style="color: black; "><ol type="1"> <li>Abnormality in β-oxidation of fatty acids (FAs)
<blockquote style="color: blue; ">Fatty liver of pregnancy: dysfunction in β-oxidation FAs; deliver baby</blockquote></li><li>Fatal to mother and fetus unless the baby is delivered</li> </ol>
</div></html>
<html><a name="HC018017"></a><span macro="tag [[21 Female Reproductive Disorders and Breast Disorders]] [[Chapter 21]]"></span> <br> <br><a name="P018013"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hypertension, proteinuria, dependent pitting edema in third trimester</li><li>Liver cell necrosis around portal triads (zone 1)
<blockquote style="color: blue; ">Preeclampsia: periportal triad liver cell necrosis; HELLP syndrome</blockquote></li><ul> <li>Increased serum transaminases</li> </ul><li>HELLP syndrome</li><ol type="a"> <li><i>H</i>emolytic anemia with schistocytes (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li><li><i>El</i>evated serum transaminases</li><li><i>L</i>ow <i>p</i>latelets</li><ul> <li>Due to disseminated intravascular coagulation (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>)</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC018018"></a> <br><a name="P018014"></a><div class="PA" style="color: black; "><ul> <li>Acute liver failure with encephalopathy within 8 weeks of hepatic dysfunction</li><ol type="1"> <li>Causes
<blockquote style="color: blue; ">Fulminant hepatic failure: viral hepatitis most common overall cause</blockquote></li><ol type="a"> <li>Viral hepatitis (most common overall cause)</li><li>Drugs (e.g., acetaminophen most common cause)</li><li>Reye syndrome</li> </ol><li>Gross and microscopic findings
<blockquote style="color: blue; ">Fulminant hepatitis: acetaminophen most common drug cause</blockquote></li><ol type="a"> <li>Wrinkled capsular surface due to loss of hepatic parenchyma</li><li>Dull red to yellow necrotic parenchyma with blotches of green (bile)</li> </ol><li>Clinical findings</li><ul> <li>Hepatic encephalopathy (see section VII), jaundice</li> </ul><li>Laboratory findings
<blockquote style="color: blue; ">Fulminant hepatic failure: ↓ transaminases, ↑ PT and ammonia</blockquote></li><ol type="a"> <li>Decrease in transaminases</li><ul> <li>Liver parenchyma is destroyed.</li> </ul><li>Increase in PT and ammonia</li> </ol><li>Treatment (refer to section VII, Cirrhosis)</li> </ol> </ul>
</div></html>
![[18.III.A.Summary of important infectious diseases (Table 18-6 and Fig. 18-4)]]
<<tiddler [[18.III.A.Summary of important infectious diseases (Table 18-6 and Fig. 18-4)]]>>
![[18.III.B.Autoimmune hepatitis]]
<<tiddler [[18.III.B.Autoimmune hepatitis]]>>
![[18.III.C.Neonatal hepatitis]]
<<tiddler [[18.III.C.Neonatal hepatitis]]>>
![[18.III.D.Reye syndrome]]
<<tiddler [[18.III.D.Reye syndrome]]>>
![[18.III.E.Acute fatty liver of pregnancy]]
<<tiddler [[18.III.E.Acute fatty liver of pregnancy]]>>
![[18.III.F.Preeclampsia (refer to Chapter 21)]]
<<tiddler [[18.III.F.Preeclampsia (refer to Chapter 21)]]>>
![[18.III.G.Fulminant hepatic failure]]
<<tiddler [[18.III.G.Fulminant hepatic failure]]>>
<html><a name="HC018020"></a> <br><a name="P018016"></a><div class="PA" style="color: black; "><ul> <li>Obstruction of blood flow to the liver (i.e., hepatic artery, portal vein)</li><ol type="1"> <li>Hepatic artery thrombosis with infarction
<blockquote style="color: blue; ">Hepatic artery infarction: uncommon due to dual blood supply</blockquote></li><ol type="a"> <li>Liver infarction is uncommon because of a dual blood supply.</li><ul> <li>Hepatic artery and portal vein tributaries normally empty blood into the sinusoids.</li> </ul><li>Causes</li><ul> <li>(1) Liver transplant rejection
<blockquote style="color: blue; ">Hepatic artery infarction: liver transplant rejection, PAN</blockquote></li><li>(2) Vasculitis due to polyarteritis nodosa (PAN)</li> </ul> </ol><li>Portal vein thrombosis</li><ol type="a"> <li>Causes</li><ul> <li>(1) Pylephlebitis (inflammation of portal vein)</li><ul> <li>(a) Most often due to acute appendicitis</li><li>(b) Air in portal vein from bacterial gas</li> </ul><li>(2) Polycythemia vera</li><li>(3) Hepatocellular carcinoma
<blockquote style="color: blue; ">Portal vein thrombosis: ascites, portal hypertension, no hepatomegaly; air in portal vein</blockquote></li><ul> <li>Tumor invasion of the portal vein</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Portal hypertension, ascites, splenomegaly</li><li>(2) <i>No</i> hepatomegaly</li> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC018021"></a> <br><a name="P018017"></a><div class="PA" style="color: black; "><ul> <li>Intrahepatic obstruction to sinusoidal blood flow</li><ol type="1"> <li>Causes</li><ol type="a"> <li>Cirrhosis (see section VII)
<blockquote style="color: blue; ">Intrahepatic obstruction to blood flow: cirrhosis most common cause</blockquote></li><li>Centrilobular hemorrhagic necrosis</li><li>Peliosis hepatis</li><li>Sickle cell disease (see <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li> </ol><li>Centrilobular hemorrhagic necrosis</li><ol type="a"> <li>Most often due to left-sided heart failure (LHF) and right-sided heart failure (RHF)</li><ul> <li>(1) LHF decreases cardiac output causing hypoperfusion of the liver.
<blockquote style="color: blue; ">Centrilobular necrosis: combined LHF and RHF; "nutmeg" liver</blockquote></li><ul> <li>Causes ischemic necrosis of hepatocytes located around central vein (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li> </ul><li>(2) RHF causes a backup of systemic venous blood into the central veins and sinusoids.</li> </ul><li>Enlarged liver with a mottled red appearance ("nutmeg" liver) (<span>[[Fig. 18-5|Figure 18-5]]</span>)</li><ul> <li>(1) Congestion of central veins and sinusoids</li><li>(2) Necrosis of hepatocytes around the central vein</li> </ul><li>Clinical findings</li><ul> <li>(1) Painful hepatomegaly with or without jaundice</li><li>(2) Increased transaminases caused by ischemic necrosis
<blockquote style="color: blue; ">Centrilobular necrosis: may progress to cardiac cirrhosis</blockquote></li><li>(3) May progress to cardiac cirrhosis</li><ul> <li>Fibrosis around central veins</li> </ul> </ul><li>Treatment</li><ul> <li>Treat heart failure</li> </ul> </ol><li>Peliosis hepatis</li><ol type="a"> <li>Sinusoidal dilation due to blood</li><li>Causes</li><ul> <li>(1) Anabolic steroids
<blockquote style="color: blue; ">Peliosis hepatis: anabolic steroids, <i>Bartonella henselae</i></blockquote></li><li>(2) <i>Bartonella henselae</i> causing bacillary angiomatosis (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)</li><ul> <li>Occurs in AIDS</li> </ul> </ul><li>Potential for intraperitoneal hemorrhage</li> </ol> </ol> </ul>
</div></html>
<html><a name="HC018022"></a> <br><a name="P018018"></a><div class="PA" style="color: black; "><ul> <li>Obstruction of blood flow out of the liver (e.g., hepatic vein)</li><ol type="1"> <li>Causes</li><ol type="a"> <li>Hepatic vein thrombosis</li><li>Veno-occlusive disease</li> </ol><li>Hepatic vein thrombosis</li><ol type="a"> <li>Causes</li><ul> <li>(1) Polycythemia vera
<blockquote style="color: blue; ">Polycythemia vera: most common cause of hepatic vein thrombosis</blockquote></li><ul> <li>Most common cause (up to 40% of cases)</li> </ul><li>(2) Hypercoagulable state (20% of cases)</li><ul> <li>(a) Oral contraceptive pills</li><li>(b) Protein C/S deficiency</li><li>(c) Antiphospholipid syndrome</li> </ul><li>(3) Hepatocellular carcinoma (<5% of cases)</li><ul> <li>Invades hepatic vein</li> </ul> </ul><li>Clinical findings
<blockquote style="color: blue; ">Hepatic vein thrombosis: hepatomegaly, portal hypertension, ascites</blockquote></li><ul> <li>(1) Enlarged, painful liver</li><li>(2) Portal hypertension, ascites, splenomegaly</li><li>(3) High mortality rate</li> </ul><li>Laboratory findings</li><ul> <li>(1) Increased transaminases</li><li>(2) Increased PT</li> </ul><li>Diagnosis</li><ul> <li>(1) Ultrasound with pulsed Doppler first-line test</li><li>(2) MRI</li> </ul><li>Treatment</li><ul> <li>(1) Anticoagulation</li><li>(2) In situ thrombolysis</li><li>(3) Stenting, various shunts</li> </ul><li>Prognosis</li><ul> <li>Approximately 75% mortality rate in first year</li> </ul> </ol><li>Veno-occlusive disease
<blockquote style="color: blue; ">Veno-occlusive disease: complication of bone marrow transplantation</blockquote></li><ol type="a"> <li>Complication of bone marrow transplantation</li><li>Collagen develops around the central veins.</li> </ol> </ol> </ul>
</div></html>
![[18.IV.A.Prehepatic obstruction to blood flow]]
<<tiddler [[18.IV.A.Prehepatic obstruction to blood flow]]>>
![[18.IV.B.Intrahepatic obstruction to blood flow]]
<<tiddler [[18.IV.B.Intrahepatic obstruction to blood flow]]>>
![[18.IV.C.Posthepatic obstruction to blood flow]]
<<tiddler [[18.IV.C.Posthepatic obstruction to blood flow]]>>
![[18.IV.D.Hematobilia]]
<<tiddler [[18.IV.D.Hematobilia]]>>
<html><a name="HC018023"></a> <br><a name="P018019"></a><div class="PA" style="color: black; "><ul> <li>Blood in the bile in patients with trauma to the liver
<blockquote style="color: blue; ">Hematobilia: blood in bile from liver trauma</blockquote></li> </ul>
</div></html>
<html><a name="HC018051"></a> <br><a name="P018052"></a><div class="PA" style="color: black; "><ol type="1"> <li>Choledochal cyst
<blockquote style="color: blue; ">Choledochal cyst: most common biliary tract cyst in children; pain with intermittent jaundice</blockquote></li><ol type="a"> <li>Most common cyst in biliary tract in children younger than 10 years old</li><li>Clinical findings</li><ul> <li>(1) Abdominal pain with persistent or intermittent jaundice</li><li>(2) Increased incidence of cholelithiasis, cholangiocarcinoma, and cirrhosis</li> </ul><li>Diagnosis</li><ul> <li>(1) Ultrasound is screening test of choice</li><li>(2) Endoscopic retrograde cholangiopancreatography (ERCP) or transhepatic cholangiography</li><ul> <li>(a) Useful in identifying intra- and extrahepatic cysts</li><li>(b) Useful in identifying sites of obstruction</li> </ul> </ul><li>Treatment is surgery.
<blockquote style="color: blue; ">Cystic diseases: increased risk for cholangiocarcinoma</blockquote></li> </ol><li>Caroli disease</li><ol type="a"> <li>Autosomal dominant and recessive types</li><li>Segmental dilatation of intrahepatic bile ducts</li><li>Portal tract fibrosis</li><li>Clinical findings</li><ul> <li>(1) Association with polycystic kidney disease
<blockquote style="color: blue; ">Caroli disease: association with juvenile polycystic kidney disease</blockquote></li><ul> <li>Autosomal recessive types in children or autosomal dominant in adults</li> </ul><li>(2) Increased incidence of cholangiocarcinoma</li><li>(3) Increased incidence of the following:</li><ul> <li>Intrahepatic cholelithiasis, cholangitis, hepatic abscesses, portal hypertension</li> </ul> </ul><li>Treatment</li><ul> <li>(1) Surgical resection of an involved lobe</li><li>(2) Liver transplantation</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC018052"></a> <br><a name="P018053"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common malignancy of bile ducts</li><li>Causes of cholangiocarcinoma</li><ol type="a"> <li>Primary sclerosing cholangitis (see section VI)
<blockquote style="color: blue; ">Primary sclerosing cholangitis: most common cause of cholangiocarcinoma</blockquote></li><ul> <li>Most common cause in the United States</li> </ul><li><i>Clonorchis sinensis</i> (Chinese liver fluke)</li><li>Thorotrast (thorium dioxide)</li><li>Choledochal cyst, Caroli disease</li> </ol><li>Locations</li><ol type="a"> <li>Ampulla or common bile duct (most common sites)</li><li>Junction of right/left hepatic duct (Klatskin tumor)</li><li>Intrahepatic</li> </ol><li>Clinical findings</li><ol type="a"> <li>Obstructive jaundice</li><li>Palpable gallbladder (Courvoisier's sign)</li><ul> <li>Only mid-common bile duct or ampulla locations</li> </ul><li>Hepatomegaly</li> </ol><li>Diagnosis</li><ul> <li>Ultrasound, ERCP</li> </ul><li>Treatment is surgery.</li> </ol>
</div></html>
<html><a name="HC018053"></a> <br><a name="PB018010"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Estrogen</b> increases CH stone formation by a number of different mechanisms. Estrogen increases the synthesis of high-density lipoprotein (HDL), which transports cholesterol from peripheral tissue to the liver for excretion in bile. Estrogen also upregulates low-density lipoprotein (LDL) receptor synthesis in hepatocytes and increases HMG-CoA reductase activity, the rate-limiting enzyme in CH synthesis.
<blockquote style="color: blue; ">Estrogen: ↑ HDL and delivery CH to liver; ↑ LDL receptors and HMG-CoA reductase activity</blockquote></div><a name="P018054"></a><div class="PA" style="color: black; "><ol type="1"> <li>Components of bile
<blockquote style="color: blue; ">Bile: bile salts/acid, phospholipid, protein, CB, free CH, electrolytes, biocarbonate</blockquote></li><ol type="a"> <li>Bile salts/acids (∼67%)</li><ul> <li>(1) Hepatic product of cholesterol (CH) metabolism</li><li>(2) Water soluble</li><li>(3) Detergent action renders CH soluble in bile.</li> </ul><li>Phospholipid (22%)</li><ul> <li>(1) Mainly lecithin</li><li>(2) Hydrophobic</li><li>(3) Solubilizes CH in bile</li> </ul><li>Protein (4.5%), free CH (4%), conjugated bilirubin (0.3%)</li><li>Water, electrolytes, bicarbonate</li> </ol><li>Types</li><ol type="a"> <li>Cholesterol stones (75%) (<span>[[Fig. 18-15|Figure 18-15]]</span>)
<blockquote style="color: blue; ">Cholesterol gallstones: most common stone</blockquote></li><ul> <li>(1) Usually stones are of mixed composition.</li><li>(2) Stones contain CH, calcium carbonate, some bilirubin pigment.</li><ul> <li>Can be radiopaque if they contain calcium carbonate</li> </ul><li>(3) Rarely are stones purely CH.</li><li>(4) CH stones are radiolucent.</li> </ul><li>Pigment stones</li><ul> <li>(1) Black pigment stones (<span>[[Fig. 18-16|Figure 18-16]]</span>)
<blockquote style="color: blue; ">Black pigment gallstone: sign of extravascular hemolysis; calcium bilirubinate</blockquote></li><ul> <li>(a) Sign of chronic extravascular hemolytic anemia</li><ul> <li>Examples-sickle cell anemia, hereditary spherocytosis</li> </ul><li>(b) Excess bilirubin in bile produces calcium bilirubinate</li> </ul><li>(2) Brown pigment stones
<blockquote style="color: blue; ">Brown pigment gallstones: sign of CBD infection</blockquote></li><ul> <li>(a) Sign of infection in the common bile duct (CBD)</li><li>(b) Commonly seen in Asians</li> </ul> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Cholesterol stones</li><ul> <li>(1) Supersaturation of bile with cholesterol
<blockquote style="color: blue; ">CH gallstones: ↑ CH in bile, ↓ bile salts and lecithin</blockquote></li><li>(2) Decreased bile salts/acids (refer to <span macro="tag [[17 Gastrointestinal Disorders]] [[Chapter 17]]"></span>) and lecithin</li><ul> <li>Both normally solubilize cholesterol in bile</li> </ul><li>(3) Risk factors</li><ul> <li>(a) Female > 40 years old</li><li>(b) Obesity</li><ul> <li>Cholesterol is increased in bile.
<blockquote style="color: blue; ">CH gallstones: female, fat, forty, fertile</blockquote></li> </ul><li>(c) Use of oral contraceptive pills</li><li>(d) Rapid weight loss; use of lipid-lowering drugs</li><li>(e) Native Americans (e.g., Pima and Navajo Indians)</li> </ul> </ul> </ol><li>Complications associated with stones</li><ol type="a"> <li>Cholecystitis (most common)</li><li>CBD obstruction
<blockquote style="color: blue; ">Stone complications: cholecystitis, CBD obstruction, cancer, acute pancreatitis</blockquote></li><li>Gallbladder cancer</li><li>Acute pancreatitis</li> </ol> </ol>
</div></html>
<html><a name="HC018054"></a> <br><a name="P018055"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>More common in women than in men</li><li>Occurs most often during fifth and sixth decades
<blockquote style="color: blue; ">CH gallstones: ↑ CH in bile, ↓ bile salts and lecithin</blockquote></li><li>High incidence in Native Americans (see above)</li><li>Associated with gallstones in >95% of cases</li> </ol><li>Stages of development of acute cholecystitis</li><ol type="a"> <li>Stage 1</li><ul> <li>(1) Stone lodges in the cystic duct
<blockquote style="color: blue; ">Stage 1: stone lodges in cystic duct; midepigastric colicky pain</blockquote></li><ul> <li>(a) Stimulus of food causes gallbladder (GB) contraction.</li><li>(b) Stone is forced into the cystic duct.</li> </ul><li>(2) Midepigastric colicky pain occurs.</li><ul> <li>Due to GB contraction against obstructed cystic duct</li> </ul><li>(3) Nausea and vomiting <i>without</i> pain relief</li> </ul><li>Stage 2</li><ul> <li>(1) Stone becomes impacted in the cystic duct.
<blockquote style="color: blue; ">Stage 2: stone impacts in cystic duct; pain shift to RUQ; radiation to right scapular shoulder</blockquote></li><li>(2) Mucus accumulates behind the obstruction.</li><li>(3) Chemical irritation of mucosa</li><li>(4) Bacterial overgrowth (no invasion)</li><ul> <li>(a) Most commonly <i>Escherichia coli</i></li><li>(b) Less commonly-<i>Enterococci</i>, <i>Bacteroides fragilis</i>, <i>Clostridium</i> sp</li> </ul><li>(5) Pain shifts to right upper quadrant (RUQ)</li><ul> <li>(a) Dull, continuous aching pain</li><li>(b) Pain radiation to right scapular/shoulder</li> </ul> </ul><li>Stage 3
<blockquote style="color: blue; ">Stage 3: bacterial invasion GB wall; + Murphy sign; subsides if stone falls out</blockquote></li><ul> <li>(1) Bacterial invasion of GB wall</li><li>(2) Localized peritonitis with rebound tenderness</li><li>(3) Positive Murphy sign (see below)</li><li>(4) Absolute neutrophilic leukocytosis</li><li>(5) Attack subsides if the stone falls out of the cystic duct</li><ul> <li>(a) Approximately 90% subside over 37 days</li><li>(b) If not, it perforates (next stage)</li> </ul> </ul><li>Stage 4
<blockquote style="color: blue; ">Stage 4: perforation</blockquote></li><ul> <li>(1) Perforation</li><ul> <li>Wall tension from GB distention compresses lumens of intramural vessels → gangrenous necrosis</li> </ul> </ul> </ol><li>Other causes <i>not</i> associated with stones</li><ol type="a"> <li>AIDS</li><ul> <li>Infection with cytomegalovirus (CMV) or <i>Cryptosporidium</i></li> </ul><li>Severe volume depletion</li> </ol><li>Clinical findings</li><ol type="a"> <li>Fever</li><li>See stages of acute cholecystitis</li><li>Vomiting (75%)</li><li>Radiation of pain to the right scapula/shoulder
<blockquote style="color: blue; ">Pain radiation: right scapula/shoulder</blockquote></li><li>Murphy sign</li><ul> <li>Pain when the GB hits the examiner's finger on patient inspiration</li> </ul><li>Jaundice (25%)</li><ul> <li>(1) Usually indicates CBD stone</li><li>(2) Indication for CBD exploration</li> </ul><li>Palpable gallbladder (15%)</li> </ol><li>Laboratory findings</li><ol type="a"> <li>Absolute neutrophilic leukocytosis with left shift</li><ul> <li>WBC counts > 12,000 cells/mm<sup>3</sup> (>70%)</li> </ul><li>Increased serum AST/ALP</li><li>Increased serum amylase suggests associated pancreatitis</li><li>Increased serum bilirubin > 4 mg/dL unusual</li><ul> <li>Usually indicates stone in CBD</li> </ul> </ol><li>Tests to identify stones</li><ol type="a"> <li>Ultrasound is the preferred initial test (<span>[[Fig. 18-17|Figure 18-17]]</span>)
<blockquote style="color: blue; ">Ultrasound: gold standard for diagnosis</blockquote></li><ul> <li>(1) Gold standard test (>98% sensitivity)</li><li>(2) Detects stones > 12 mm in diameter</li><li>(3) Detects sludge; evaluates GB wall thickness</li><li>(4) <i>Not</i> effective in identifying CBD stones (<30% sensitivity)</li> </ul><li>Plain film</li><ul> <li>Only 20% are radiopaque</li> </ul><li>Hepatobiliary iminodiacetic acid (HIDA) radionuclide scan
<blockquote style="color: blue; ">HIDA scan: identifies stone in cystic duct and CBD</blockquote></li><ul> <li>(1) Identifies stone(s) in cystic duct</li><ul> <li>No visualization of GB</li> </ul><li>(2) No tracer in duodenum</li><ul> <li>Indicates CBD stone</li> </ul> </ul> </ol><li>Indications for CBD exploration</li><ol type="a"> <li>Jaundice
<blockquote style="color: blue; ">Jaundice: indication for CBD exploration</blockquote></li><li>CBD dilatation > 12 mm</li><li>No stones in GB</li><li>Acute pancreatitis</li> </ol><li>Treatment</li><ol type="a"> <li>Cholecystectomy (laparoscope preferred)</li><li>ERCP with sphincterotomy to extract stone in CBD
<blockquote style="color: blue; ">Treatment cholecystitis: surgery via laparoscope</blockquote></li><li>Meperidine for pain</li><ul> <li>(1) Do <i>not</i> use morphine</li><li>(2) Contracts the sphincter of Oddi and worsens pain
<blockquote style="color: blue; ">Pain in cholecystitis: meperidine <i>not</i> morphine</blockquote></li> </ul><li>Piperacillin-tazobactam</li> </ol> </ol>
</div></html>
<html><a name="HC018055"></a> <br><a name="P018056"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Chronic cholecystitis: most common symptomatic disorder of the GB</blockquote>
<ol type="1"> <li>Epidemiology</li><ul> <li>Most common symptomatic disorder of GB</li> </ul><li>Pathogenesis</li><ol type="a"> <li>Cholelithiasis with repeated attacks of minor inflammation</li><li>Chemical inflammation (infection is uncommon)
<blockquote style="color: blue; ">Chronic cholecystitis: chemical inflammation</blockquote></li> </ol><li>Clinical findings</li><ol type="a"> <li>Severe, persistent pain 12 hours postprandially in the evening</li><li>Pain radiates into the right scapular area.</li><li>Recurrent epigastric distress, belching, and bloating</li> </ol><li>Treatment is laparoscopic cholecystectomy.</li> </ol>
</div></html>
<html><a name="HC018056"></a> <br><a name="P018057"></a><div class="PA" style="color: black; "><ol type="1"> <li>Excess cholesterol in bile</li><ol type="a"> <li>Cholesterol deposits in macrophages</li><li>Produces a yellow, speckled mucosal surface
<blockquote style="color: blue; ">Cholesterolosis: excess CH in bile; speckled yellow mucosal surface</blockquote></li> </ol><li><i>No</i> clinical significance</li> </ol>
</div></html>
<html><a name="HC018057"></a> <br><a name="P018058"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Hydrops: chronic obstruction of cystic duct</blockquote>
<ol type="1"> <li>Chronic obstruction of cystic duct</li><li>Distended GB with atrophy of the mucosa/muscle</li><li>Clear secretions</li><li>Treatment is surgery.</li> </ol>
</div></html>
![[18.IX.A.Cystic diseases]]
<<tiddler [[18.IX.A.Cystic diseases]]>>
![[18.IX.B.Cholangiocarcinoma]]
<<tiddler [[18.IX.B.Cholangiocarcinoma]]>>
![[18.IX.C.Gallstones (cholelithiasis)]]
<<tiddler [[18.IX.C.Gallstones (cholelithiasis)]]>>
![[18.IX.D.Acute cholecystitis]]
<<tiddler [[18.IX.D.Acute cholecystitis]]>>
![[18.IX.E.Chronic cholecystitis]]
<<tiddler [[18.IX.E.Chronic cholecystitis]]>>
![[18.IX.F.Cholesterolosis]]
<<tiddler [[18.IX.F.Cholesterolosis]]>>
![[18.IX.G.Hydrops of gallbladder]]
<<tiddler [[18.IX.G.Hydrops of gallbladder]]>>
![[18.IX.H.Gallbladder adenocarcinoma]]
<<tiddler [[18.IX.H.Gallbladder adenocarcinoma]]>>
<html><a name="HC018058"></a> <br><a name="P018059"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Dominant in elderly women</li><li>Poor prognosis</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Cholelithiasis (95% of cases)
<blockquote style="color: blue; ">GB cancer: association with GB stones; porcelain GB</blockquote></li><li>Porcelain gallbladder</li><ul> <li>(1) Gallbladder with dystrophic calcification</li><li>(2) Mandatory removal of GB
<blockquote style="color: blue; ">Porcelain gallbladder: ↑ risk for gallbladder cancer; immediate surgery</blockquote></li><ul> <li>(a) Approximately 50% risk for progression to cancer</li><li>(b) Immediate surgical removal is warranted.</li> </ul> </ul> </ol><li>Treatment is surgery.</li><ol type="a"> <li>Majority have already locally invaded liver or porta hepatis at discovery.</li><li>Five-year survival rate < 2%</li> </ol> </ol>
</div></html>
<html><a name="HC018025"></a> <br><a name="P018021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Risk factors for alcohol-related liver disease (refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>)</li><li>Pathways for alcohol metabolism (refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>)</li><li>Types of liver disease
<blockquote style="color: blue; ">Alcohol liver disease: fatty change, hepatitis, cirrhosis</blockquote></li><ol type="a"> <li>Fatty change is the most common type of disease (see <span>[[Fig. 1-8|Figure 1-8]]</span>).</li><ul> <li>(1) Substrates of alcohol metabolism are used to synthesize liver triglyceride.</li><li>(2) Clinical findings</li><ul> <li>Tender hepatomegaly <i>without</i> fever or neutrophilic leukocytosis</li> </ul><li>(3) Treatment</li><ul> <li>Alcohol rehabilitation</li> </ul> </ul><li>Alcoholic hepatitis</li><ul> <li>(1) Pathogenesis</li><ul> <li>(a) Genetic predisposition is likely.</li><li>(b) Due to acetaldehyde damage to hepatocytes
<blockquote style="color: blue; ">Alcoholic hepatitis: acetaldehyde damages hepatocytes</blockquote></li><li>(c) Stimulation of collagen synthesis around the central vein</li><ul> <li>Perivenular fibrosis</li> </ul> </ul><li>(2) Microscopic findings</li><ul> <li>(a) Fatty change with neutrophil infiltration</li><li>(b) Mallory bodies</li><ul> <li>Damaged cytokeratin intermediate filaments in hepatocytes (see <span>[[Fig. 1-7|Figure 1-7]]</span>)</li> </ul><li>(c) Perivenular fibrosis</li> </ul><li>(3) Clinical findings
<blockquote style="color: blue; ">Alcoholic hepatitis: fatty change, neutrophil infiltration, Mallory bodies</blockquote></li><ul> <li>(a) Painful hepatomegaly</li><li>(b) Fever, neutrophilic leukocytosis, ascites, hepatic encephalopathy</li><li>(c) May progress to alcoholic cirrhosis</li> </ul><li>(4) Laboratory findings</li><ul> <li>(a) Absolute neutrophilic leukocytosis</li><li>(b) Serum aspartate aminotransferase (AST) > alanine aminotransferase (ALT)</li><li>(c) Increased serum alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT)</li><ul> <li>Serum GGT disproportionately increase to ALP (see <span>[[Table 18-2|Table 18-2. LIVER FUNCTION TESTS]]</span>)
<blockquote style="color: blue; ">Alcoholic hepatitis: acetaldehyde damages hepatocytes</blockquote></li> </ul><li>(d) Thrombocytopenia in some cases</li><li>(e) Hypoglycemia in some cases</li> </ul><li>(5) Treatment</li><ul> <li>(a) Mandatory to stop drinking</li><li>(b) Corticosteroids helpful in some cases</li> </ul> </ul><li>Cirrhosis (see section VII)</li> </ol><li>Laboratory findings (refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>; see <span>[[Fig. 6-1|Figure 6-1]]</span>)
<blockquote style="color: blue; ">Intrahepatic fibrosis: methotrexate, amiodarone</blockquote></li> </ol>
</div></html>
![[18.V.A.Alcohol-related disorders]]
<<tiddler [[18.V.A.Alcohol-related disorders]]>>
![[18.V.B.Chemical- and drug-induced liver disease (Table 18-7)]]
<<tiddler [[18.V.B.Chemical- and drug-induced liver disease (Table 18-7)]]>>
<html><a name="HC018026"></a><span>[[Table 18-7|Table 18-7. DRUG AND CHEMICAL-INDUCED LIVER DISEASES]]</span> <br> <br> </html>
<html><a name="HC018028"></a> <br><a name="P018022"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Intrahepatic cholestasis: OCP, anabolic steroids</blockquote>
<ol type="1"> <li>Intrahepatic cholestasis</li><ol type="a"> <li>Blockage of the intrahepatic bile ducts</li><li>Causes</li><ul> <li>(1) Drugs (e.g., oral contraceptive pills [OCPs], anabolic steroids)</li><li>(2) Neonatal hepatitis</li><li>(3) Pregnancy-induced cholestasis (estrogen)</li> </ul> </ol><li>Extrahepatic cholestasis
<blockquote style="color: blue; ">Extrahepatic cholestasis: most commonly caused by a stone in CBD</blockquote></li><ol type="a"> <li>Blockage of common bile duct (CBD)</li><li>Causes</li><ul> <li>(1) Stone usually originating from the gallbladder</li><li>(2) Primary sclerosing cholangitis</li><li>(3) Extrahepatic biliary atresia</li><li>(4) Carcinoma head of pancreas</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC018029"></a> <br><a name="P018023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Enlarged, greenish liver</li><li>Bile ducts distended with bile (<span>[[Fig. 18-6|Figure 18-6]]</span>), bile lakes, bile infarcts</li> </ol>
</div></html>
<html><a name="HC018030"></a> <br><a name="P018024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Jaundice with pruritus</li><ul> <li>Pruritus due to bile salts deposited in skin</li> </ul><li>Malabsorption</li><ul> <li>Bile salts do <i>not</i> enter the small intestine.</li> </ul><li>Cholesterol deposits in skin</li><ol type="a"> <li>Due to cholesterol in bile</li><li>Example-xanthelasma (see <span>[[Fig. 9-2B|Figure 9-2]]</span>)</li> </ol><li>Light-colored stools</li><ul> <li>Due to a lack of urobilin</li> </ul> </ol>
</div></html>
<html><a name="HC018031"></a><span>[[Box 18-1D|BOX 18-1 COMMON CAUSES OF JAUNDICE]]</span> <br> <br><a name="P018025"></a><div class="PA" style="color: black; "><ol type="1"> <li>CB > 50%</li><li>Bilirubinuria</li><li>Absent urine UBG</li><li>Increase in serum ALP and GGT
<blockquote style="color: blue; ">Cholestasis: urine UBG 0, urine bilirubin ++</blockquote></li> </ol>
</div></html>
<html><a name="HC018032"></a> <br><a name="P018026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Due to estrogen inhibition of intrahepatic bile secretion
<blockquote style="color: blue; ">Cholestasis in pregnancy: effect of estrogen on intrahepatic bile secretion</blockquote></li><li><i>Not</i> dangerous to the fetus or mother</li> </ol>
</div></html>
<html><a name="HC018033"></a> <br><a name="P018027"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Extrahepatic biliary atresia: jaundice in newborn</blockquote>
<ol type="1"> <li>Cause of jaundice in newborns</li><li>Inflammatory destruction of all or part of the extrahepatic bile ducts</li><li>Bile duct proliferation in the triads</li><li>Common indication for liver transplantation in a child</li> </ol>
</div></html>
<html><a name="HC018034"></a> <br><a name="P018028"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Obliterative fibrosis of intrahepatic and extrahepatic bile ducts
<blockquote style="color: blue; ">PSC: obliterative fibrosis intrahepatic and extrahepatic bile ducts</blockquote></li><li>Primary disease</li><ul> <li>(1) Genetic predisposition</li><ul> <li>Association with HLA-DR52a (100%) and HLA-Cw7 (86%)</li> </ul><li>(2) Male dominant (70%); usually <45 years old</li><li>(3) Associations</li><ul> <li>(a) Inflammatory bowel disease (70%)
<blockquote style="color: blue; ">PSC: strong association with ulcerative colitis > Crohn's disease</blockquote></li><ul> <li>Ulcerative colitis > Crohn's disease</li> </ul><li>(b) Other sclerosing disorders</li><ul> <li>Retroperitoneal and mediastinal sclerosing fibrosis</li> </ul> </ul><li>(4) Complications
<blockquote style="color: blue; ">PSC: cirrhosis, cholangiocarcinoma</blockquote></li><ul> <li>(a) Cirrhosis</li><li>(b) Cholangiocarcinoma</li> </ul> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Jaundice</li><li>Pruritus</li><ul> <li>Deposition of bile salts/acids in skin</li> </ul><li>Hepatosplenomegaly</li> </ol><li>Laboratory findings</li><ol type="a"> <li>CB > 50%</li><li>Bilirubinuria</li><li>Absent urine UBG</li><li>Increase in serum ALP and GGT</li> </ol><li>Diagnosis</li><ol type="a"> <li>Endoscopic retrograde cholangiopancreatography (ERCP)
<blockquote style="color: blue; ">PSC: ERCP diagnostic; "beading" of bile ducts</blockquote></li><li>Dye study shows narrowing and dilation of bile ducts ("beading")</li> </ol><li>Treatment</li><ol type="a"> <li>Immunosuppressants</li><ul> <li>Corticosteroids, azathioprine, methotrexate</li> </ul><li>Invariably require a liver transplant</li> </ol> </ol>
</div></html>
![[18.VI.A.Types of cholestatic liver disease]]
<<tiddler [[18.VI.A.Types of cholestatic liver disease]]>>
![[18.VI.B.Gross and microscopic]]
<<tiddler [[18.VI.B.Gross and microscopic]]>>
![[18.VI.C.Clinical findings]]
<<tiddler [[18.VI.C.Clinical findings]]>>
![[18.VI.D.Laboratory findings (see Box 18-1D)]]
<<tiddler [[18.VI.D.Laboratory findings (see Box 18-1D)]]>>
![[18.VI.E.Benign intrahepatic cholestasis of pregnancy]]
<<tiddler [[18.VI.E.Benign intrahepatic cholestasis of pregnancy]]>>
![[18.VI.F.Extrahepatic biliary atresia]]
<<tiddler [[18.VI.F.Extrahepatic biliary atresia]]>>
![[18.VI.G.Primary sclerosing cholangitis (PSC)]]
<<tiddler [[18.VI.G.Primary sclerosing cholangitis (PSC)]]>>
<html><a name="HC018036"></a> <br><a name="P018031"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hepatocyte reaction to injury (<span>[[Fig. 18-7|Figure 18-7]]</span>)</li><li>Lack normal liver architecture (<span>[[Fig 18-8|Figure 18-8]]</span>)</li><ul> <li>Lack of portal triads and sinusoids</li> </ul><li>Surrounded by bands of fibrosis</li><li>Compress sinusoids and central veins
<blockquote style="color: blue; ">Regenerative nodules: produce intrasinusoidal hypertension</blockquote></li><ol type="a"> <li>Intrasinusoidal hypertension</li><li>Reduction in the number of functional sinusoids</li><li>Increase in hydrostatic pressure in portal vein</li> </ol> </ol>
</div></html>
<html><a name="HC018037"></a> <br><a name="P018032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Alcoholic liver disease (most common)
<blockquote style="color: blue; ">Alcoholic liver disease: most common cause of cirrhosis</blockquote></li><li>Postnecrotic cirrhosis (HBV, HCV)</li><li>Autoimmune disease</li><ol type="a"> <li>Primary biliary cirrhosis</li><li>Autoimmune hepatitis (see section III)</li> </ol><li>Metabolic diseases</li><ol type="a"> <li>Hemochromatosis</li><li>Wilson's disease</li><li>α<sub>1</sub>-Antitrypsin deficiency</li><li>Galactosemia</li> </ol> </ol>
</div></html>
<html><a name="HC018038"></a> <br><a name="PB018005"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Ammonia</b> derives from metabolism of amino acids and from the release of ammonia from amino acids by bacterial ureases in the bowel. Ammonia (NH<sub>3</sub>) is diffusible and is reabsorbed into the portal vein for delivery to the urea cycle where it is metabolized into urea. Ammonium (NH<sub>4</sub>) is <i>not</i> reabsorbed in the bowel and is excreted in stool. Methods for reducing ammonia in the colon include restriction of protein intake (most cost effective) and the use of oral neomycin, which destroys the colonic bacteria. Oral administration of lactulose results in the release of hydrogen ions, causing NH<sub>3</sub> to be converted to NH<sub>4</sub>, which is excreted in the feces.
<blockquote style="color: blue; ">Ammonia: derives from amino acid metabolism and urease-producing bacteria in bowel</blockquote>
<blockquote style="color: blue; ">↓ Ammonia: ↓ protein intake; antibiotics; lactulose</blockquote></div><a name="PB018006"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Peritoneal fluid analysis</b> is useful in distinguishing ascites of liver origin from ascites of peritoneal origin. The gradient between serum albumin and ascitic fluid albumin (serum albumin - ascitic fluid albumin) is very helpful in making this distinction. A difference > 1.1 g/dL is ascites of liver origin, while a difference < 1.1 g/dL is of peritoneal origin (e.g., peritonitis). Recall that ascites of liver origin is a transudate, which is a protein-poor and cell-poor fluid; hence, the expected difference between serum albumin and ascitic albumin is increased. However, ascitic fluid from peritonitis is an exudate, which is a protein-rich and cell-rich fluid; hence, the difference between serum and ascitic fluid is much less. Peritoneal fluid protein concentration and cell count are also useful. A total peritoneal fluid protein concentration < 2.5 g/dL and WBC count < 300 cells/mm<sup>3</sup> + neutrophils < 25% of the total count is consistent with a transudate, while a concentration > 2.5 g/dL and a WBC count > 300 cells/mm<sup>3</sup> + neutrophils > 25% of the total count indicates an exudate.
<blockquote style="color: blue; ">Ascites-liver vs. peritoneal: serum albumin - ascitic fluid albumin; >1.1 g/dL liver origin, <1.1 g/dL peritoneal origin</blockquote></div><a name="P018033"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hepatic failure</li><ul> <li>End-point of progressive damage to the liver</li><ol type="a"> <li>Multiple coagulation defects</li><ul> <li>(1) Due to inability to synthesize coagulation factors</li><li>(2) Produces a hemorrhagic diathesis</li> </ul><li>Hypoalbuminemia from decreased synthesis of albumin</li><ul> <li>Produces dependent pitting edema and ascites</li> </ul><li>Hepatic encephalopathy
<blockquote style="color: blue; ">Hepatic encephalopathy: reversible metabolic disorder; ↑ false neurotransmitters; ↑ serum ammonia</blockquote></li><ul> <li>(1) Reversible metabolic disorder</li><li>(2) Increase in aromatic amino acids (e.g., phenylalanine, tyrosine, tryptophan)</li><ul> <li>Converted into false neurotransmitters (e.g., γ-aminobutyric acid)</li> </ul><li>(3) Increase in serum ammonia</li><ul> <li>Due to a defective urea cycle that cannot metabolize ammonia</li> </ul><li>(4) Factors precipitating encephalopathy</li><ul> <li>(a) Increased protein (most important)</li><ul> <li>Dietary or blood in gastrointestinal tract; increases bacterial conversion of urea into ammonia</li> </ul><li>(b) Alkalosis keeps ammonia in NH<sub>3</sub> state (see earlier).</li><ul> <li>Diuretics (loop and thiazide) produce metabolic alkalosis.</li> </ul><li>(c) Sedatives
<blockquote style="color: blue; ">Precipitating factors: ↑ protein, alkalosis, sedatives, portasystemic shunts</blockquote></li><li>(d) Portasystemic shunts</li><ul> <li>Shunt ammonia away from the liver, which normally metabolizes ammonia in the urea cycle</li> </ul> </ul><li>(5) Clinical findings</li><ul> <li>(a) Alterations in the mental status
<blockquote style="color: blue; ">Hepatic encephalopathy: alterations mental status, somnolence, asterixis</blockquote></li><li>(b) Somnolence and disordered sleep rhythms</li><li>(c) Asterixis (i.e., inability to sustain posture, flapping tremor)</li><li>(d) Coma and death in late stages</li> </ul><li>(6) Treatment (see ammonia discussion)</li> </ul> </ol> </ul><li>Portal hypertension (PH)</li><ol type="a"> <li>Pathogenesis
<blockquote style="color: blue; ">Portal vein: splenic vein superior mesenteric vein</blockquote></li><ul> <li>(1) Resistance to intrahepatic blood flow due to intrasinusoidal hypertension</li><li>(2) Anastomoses between portal vein tributaries and the arterial system</li> </ul><li>Complications
<blockquote style="color: blue; ">Portal vein hypertension: due to intrasinusoidal hypertension from regenerative nodule compression</blockquote></li><ul> <li>(1) Ascites (see later)</li><li>(2) Congestive splenomegaly</li><ul> <li>(a) Increased hydrostatic pressure in splenic vein</li><li>(b) Hypersplenism with various cytopenias may occur (refer to <span macro="tag [[13 Lymphoid Tissue Disorders]] [[Chapter 13]]"></span>)</li> </ul><li>(3) Esophageal varices (refer to <span macro="tag [[17 Gastrointestinal Disorders]] [[Chapter 17]]"></span>; see <span>[[Fig. 17-9|Figure 17-9]]</span>)</li><li>(4) Hemorrhoids</li><li>(5) Periumbilical venous collaterals (caput medusae)</li> </ul><li>Shunts used in treating PH</li><ul> <li>(1) Portacaval shunt</li><ul> <li>Connects the portal vein with the vena cava</li> </ul><li>(2) Mesocaval shunt</li><ul> <li>Connects the superior mesenteric vein with the portal vein.</li> </ul><li>(3) Splenorenal
<blockquote style="color: blue; ">PH and shunts: shunts that bypass the liver can precipitate encephalopathy</blockquote></li><ul> <li>(a) Most physiologic shunt</li><li>(b) Connects the splenic vein with the renal vein</li><li>(c) Reduces PH and bleeding from varices without bypassing the liver</li> </ul><li>(4) Transjugular intrahepatic portosystemic shunt (TIPS)
<blockquote style="color: blue; ">Splenorenal shunt: does <i>not</i> bypass liver; most physiologic shunt</blockquote></li><ul> <li>(a) Metal stent connects portal vein with hepatic vein.</li><li>(b) Reduces portal vein pressure
<blockquote style="color: blue; ">TIPS: ↓ portal vein pressure; connects portal vein with hepatic vein</blockquote></li><li>(c) Increases risk for encephalopathy</li><li>(d) Used in treatment of acute esophageal bleeds (refer to <span macro="tag [[17 Gastrointestinal Disorders]] [[Chapter 17]]"></span>)</li><li>(e) Used in treating patients awaiting liver transplantation</li> </ul> </ul> </ol><li>Ascites (<span>[[Fig. 18-9|Figure 18-9]]</span>)</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Portal hypertension
<blockquote style="color: blue; ">Ascites: transudate due to alterations in Starling pressures; secondary aldosteronism</blockquote></li><ul> <li>Increase in portal vein hydrostatic pressure</li> </ul><li>(2) Hypoalbuminemia</li><ul> <li>Decreases oncotic pressure</li> </ul><li>(3) Secondary hyperaldosteronism; causes:</li><ul> <li>(a) Decreased cardiac output</li><ul> <li>Activates the renin-angiotensin-aldosterone system (retention of Na<sup>+</sup> and water)</li> </ul><li>(b) Liver is unable to metabolize aldosterone.</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Abdominal distention with a fluid wave</li><li>(2) Increased risk for spontaneous bacterial peritonitis</li> </ul> </ol><li>Hepatorenal syndrome</li><ol type="a"> <li>Reversible renal failure <i>without</i> renal parenchymal disease</li><ul> <li>Creatinine clearance < 40 mL/minute (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)</li> </ul><li>Approximately 20% of people with hepatic failure die of this syndrome.</li><li>Absence of
<blockquote style="color: blue; ">Hepatorenal syndrome: reversible renal failure <i>without</i> parenchymal disease</blockquote></li><ul> <li>(1) Shock</li><li>(2) Volume depletion</li><li>(3) Infection</li><li>(4) Obstructive or parenchymal renal disease</li> </ul><li>Preservation of renal tubular function</li><ul> <li>(1) Random urine Na<sup>+</sup> < 20 mEq/L (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)</li><li>(2) Absence of significant proteinuria (<500 mg/day) or hematuria</li> </ul><li>? Due to decreased renal blood flow</li><ul> <li>Serum blood urea nitrogen and creatinine are increased (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)</li> </ul><li>Treatment</li><ul> <li>(1) Supportive care including dialysis</li><li>(2) Vasopressin analogues</li><li>(3) Vasoconstrictors (e.g., norepinephrine, midodrine)</li><li>(4) Albumin for volume expansion
<blockquote style="color: blue; ">Hepatorenal syndrome: liver transplantation only curative treatment</blockquote></li><li>(5) Liver transplantation is the only curative treatment.</li> </ul><li>Mortality rate > 80%</li> </ol><li>Hyperestrinism in males
<blockquote style="color: blue; ">Hyperestrinism in males: gynecomastia, spider telangiectasia</blockquote></li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Liver cannot degrade estrogen and 17-ketosteroids (e.g., androstenedione).</li><li>(2) Androstenedione is aromatized into estrogen in the adipose cells.</li> </ul><li>Clinical findings</li><ul> <li>(1) Gynecomastia (see <span>[[Fig. 18-9|Figure 18-9]]</span>)</li><li>(2) Spider telangiectasia (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>) (<span>[[Fig. 18-10|Figure 18-10]]</span>)</li><li>(3) Female distribution of hair (see <span>[[Fig. 18-9|Figure 18-9]]</span>)</li> </ul> </ol> </ol>
</div></html>
![[18.VII.A.Regenerative nodules]]
<<tiddler [[18.VII.A.Regenerative nodules]]>>
![[18.VII.B.Causes]]
<<tiddler [[18.VII.B.Causes]]>>
![[18.VII.C.Complications associated with cirrhosis]]
<<tiddler [[18.VII.C.Complications associated with cirrhosis]]>>
![[18.VII.D.Postnecrotic cirrhosis]]
<<tiddler [[18.VII.D.Postnecrotic cirrhosis]]>>
![[18.VII.E.Primary biliary cirrhosis (PBC)]]
<<tiddler [[18.VII.E.Primary biliary cirrhosis (PBC)]]>>
![[18.VII.F.Secondary biliary cirrhosis]]
<<tiddler [[18.VII.F.Secondary biliary cirrhosis]]>>
![[18.VII.G.Hereditary hemochromatosis]]
<<tiddler [[18.VII.G.Hereditary hemochromatosis]]>>
![[18.VII.H.Wilson's disease (hepatolenticular degeneration)]]
<<tiddler [[18.VII.H.Wilson's disease (hepatolenticular degeneration)]]>>
![[18.VII.I.α1-Antitrypsin (AAT) deficiency]]
<<tiddler [[18.VII.I.α1-Antitrypsin (AAT) deficiency]]>>
![[18.VII.J.Laboratory test abnormalities in cirrhosis]]
<<tiddler [[18.VII.J.Laboratory test abnormalities in cirrhosis]]>>
<html><a name="HC018039"></a> <br><a name="P018034"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most often caused by chronic hepatitis due to HBV and HCV
<blockquote style="color: blue; ">Postnecrotic cirrhosis: chronic hepatitis HBV and HCV</blockquote></li><li>Increased incidence of hepatocellular carcinoma</li><ul> <li>Incidence of which virus is most common varies around the world</li> </ul> </ol>
</div></html>
<html><a name="HC018040"></a> <br><a name="P018035"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Granulomatous destruction of bile ducts in portal triads</li><li>Autoimmune disorder
<blockquote style="color: blue; ">PBC: autoimmune destruction of bile ducts in triads</blockquote></li><ul> <li>Association with other autoimmune diseases (e.g., Sjögren's syndrome)</li> </ul><li>Occurs in women (>90%) between 40 and 50 years of age</li><li>Progresses from a chronic inflammatory reaction to cirrhosis with PH
<blockquote style="color: blue; ">PBC: damage to mitochondrial proteins in bile duct epithelium in triads; destruction by CD8 T cells</blockquote></li><li>Increased risk for hepatocellular carcinoma</li> </ol><li>Pathogenesis</li><ol type="a"> <li>? Environmental insult affecting mitochondrial proteins triggering CD8 T-cell destruction of intralobular bile duct epithelium</li><li>Enzyme complex subunit in mitochondrial membrane is the autoantigen recognized by CD8 T cells
<blockquote style="color: blue; ">PBC: antimitochondrial antibodies</blockquote></li><li>Autoantibodies (antimitochondrial antibodies) develop against the mitochondria</li><ul> <li>Do <i>not</i> correlate with disease activity</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Pruritus (20-70%)</li><ul> <li>(1) Unknown etiology (<i>not</i> bile salts in skin)
<blockquote style="color: blue; ">PBC: pruritus before jaundice</blockquote></li><li>(2) Early finding well <i>before</i> jaundice appears</li> </ul><li>Painful hepatosplenomegaly</li><li>Jaundice (60%)</li><ul> <li>Late finding <i>after</i> most of the bile ducts have been destroyed
<blockquote style="color: blue; ">PBC: jaundice is a late finding</blockquote></li> </ul><li>Inflammatory arthropathy (40-70%)</li><li>Xanthelasma (40%)</li><ul> <li>(1) Late finding</li><li>(2) Due to cholesterol in bile</li> </ul><li>Kayser-Fleischer ring in cornea</li><ul> <li>Due to retention of copper</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Antimitochondrial antibodies (AMA; >90%)
<blockquote style="color: blue; ">PBC: ↑ serum ANA, AMA, IgM</blockquote></li><li>Serum ANA positive (50%)</li><li>Increase in serum IgM</li><li>Increased serum ALP and GGT</li><li>Increased serum cholesterol</li><ul> <li>Component of bile</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Budesonide + ursodeoxycholic acid</li><li>Cholestyramine for pruritus</li><li>Liver transplantation</li><ul> <li>Improves survival; 70% survive 10 years</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC018041"></a> <br><a name="P018036"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Secondary biliary cirrhosis: cystic fibrosis</blockquote>
<ol type="1"> <li>Complication of chronic extrahepatic bile duct obstruction</li><ul> <li>Example-cystic fibrosis, where bile is dehydrated (refer to <span macro="tag [[16 Upper and Lower Respiratory Disorders]] [[Chapter 16]]"></span>)</li> </ul><li><i>No</i> increase in serum AMA or IgM</li> </ol>
</div></html>
<html><a name="HC018042"></a> <br><a name="PB018007"></a><div class="BB" style="color: rgb(47, 79, 79); ">The normal function of the <b><i>HFE</i></b> gene product is to facilitate the binding of plasma transferrin (binding protein of iron) with its mucosal cell transferrin receptor so that transferrin can be endocytosed by intestinal cells. The amount of endocytosed transferrin iron determines how much mucosal cell iron is released into the plasma. In hemochromatosis, when there is a mutated <i>HFE</i> gene, mucosal cell transfer of iron to plasma transferrin is always at a maximum resulting in iron overload.</div><a name="PB018008"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Hemosiderosis</b> (secondary hemochromatosis) is caused by multiple blood transfusions (e.g., sickle cell anemia, thalassemia major), alcohol abuse (alcohol increases iron reabsorption), and well water (iron pipes). Iron deposits are more prevalent in macrophages than in parenchymal tissue.
<blockquote style="color: blue; ">Hemosiderosis: acquired iron overload disease</blockquote></div><a name="P018037"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal recessive disorder</li><ul> <li>(1) Linked to short arm of chromosome 6</li><li>(2) HLA-A3 association</li> </ul><li>Most common genetic disorder in North European ancestry</li><li>Male dominant disorder</li><ul> <li>Diagnosis usually made in fifth decade</li> </ul><li>In women, diagnosis usually made 10 to 20 years <i>after</i> menopause</li><ul> <li>Due to menses causing loss of iron</li> </ul> </ol><li>Pathogenesis
<blockquote style="color: blue; ">Hemochromatosis: unrestricted reabsorption of iron</blockquote></li><ol type="a"> <li>Unrestricted reabsorption of iron in the small intestine</li><li>Mutations involving hereditary hemochromatosis gene (<i>HFE</i>)</li><ul> <li>(1) Two missense mutations (<i>C282Y</i> and <i>H63D</i>)
<blockquote style="color: blue; ">Hemochromatosis: missense mutations <i>HFE</i> gene on chromosome 6</blockquote></li><li>(2) There is a 1:10 carrier rate in the population.</li> </ul><li>Iron stimulates the production of hydroxyl free radicals (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>).</li><ul> <li>Free radicals damage tissue and cause fibrosis.
<blockquote style="color: blue; ">Iron initiates synthesis hydroxyl free radicals</blockquote></li> </ul> </ol><li>Iron deposits in multiple organs</li><ul> <li>Liver (target organ), pancreas, heart, joints, skin, pituitary</li> </ul><li>Clinical findings</li><ol type="a"> <li>Cirrhosis (60%)</li><ul> <li>(1) Iron deposits primarily in hepatocytes (<span>[[Fig. 18-11|Figure 18-11]]</span>).</li><li>(2) Increased risk of hepatocellular carcinoma</li> </ul><li>"Bronze diabetes"</li><ul> <li>(1) Type I diabetes mellitus (60%)
<blockquote style="color: blue; ">Hemochromatosis: "bronze diabetes"</blockquote></li><ul> <li>Destruction of β-islet cells</li> </ul><li>(2) Hyperpigmentation (75%)</li><ul> <li>Iron deposits in skin and increases melanin production</li> </ul> </ul><li>Malabsorption
<blockquote style="color: blue; ">Hemochromatosis: malabsorption, restrictive cardiomyopathy, infertility</blockquote></li><ul> <li>Destruction of exocrine pancreas</li> </ul><li>Restrictive cardiomyopathy</li><li>Hypogonadism</li><ul> <li>(1) Amenorrhea in women (25%)</li><li>(2) Testicular atrophy; loss of libido in men (50%)</li> </ul><li>Degenerative joint disease (>40%)</li><ul> <li>Chondrocalcinosis (refer to <span macro="tag [[23 Musculoskeletal and Soft Tissue Disorders]] [[Chapter 23]]"></span>)</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Increased serum iron, percent saturation, and ferritin
<blockquote style="color: blue; ">Hemochromatosis: ↑ serum iron, % saturation, ferritin; ↓ TIBC</blockquote></li><ul> <li>(1) Transferrin saturation is the best screening test.</li><li>(2) Values > 45% indicate further evaluation is necessary.</li><li>(3) Decreased total iron-binding capacity (TIBC)</li><ul> <li>Transferrin synthesis is decreased when iron stores are increased (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>).
<blockquote style="color: blue; ">Hemochromatosis: % saturation best screen</blockquote></li> </ul><li>(4) Serum ferritin is primarily used to follow therapy.</li> </ul><li>Liver biopsy confirmatory test
<blockquote style="color: blue; ">Serum ferritin: used to follow therapy</blockquote></li><li>Decreased serum luteinizing hormone and follicle-stimulating hormone</li> </ol><li>Screening test for relatives</li><ul> <li><i>HFE</i> gene testing for <i>C282Y</i> mutation</li> </ul><li>Treatment</li><ol type="a"> <li>Phlebotomy until serum ferritin < 50 μg/mL, saturation < 30%</li><li>Deferoxamine (iron chelator)</li> </ol><li>Normal life expectancy if no cirrhosis</li> </ol>
</div></html>
<html><a name="HC018043"></a> <br><a name="PB018009"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Ceruloplasmin</b> is an enzyme that is synthesized in the liver. It contains 6 atoms of copper in its structure. Ceruloplasmin is secreted into the plasma where it represents 90% to 95% of the total serum copper concentration. The remaining 5% to 10% of copper is free copper that is loosely bound to albumin. Ceruloplasmin is eventually taken up and degraded by the liver. The copper that was bound to ceruloplasmin is excreted into the bile. The gene defect in Wilson's disease affects a copper transport system that produces a dual defect-decreased incorporation of copper into ceruloplasmin in the liver and decreased excretion of copper into bile. Accumulation of copper in the liver increases the formation of hydroxyl free radicals causing damage to hepatocytes. Liver disease progresses from acute hepatitis to cirrhosis. In a few years, unbound copper is released from the liver into the circulation (increased in blood and urine) where it damages the brain, kidneys, cornea, and other tissues.
<blockquote style="color: blue; ">Ceruloplasmin: enzyme synthesized in the liver that contains copper</blockquote></div><a name="P018038"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal recessive disorder</li><li>Affects men and women equally</li><li>Onset of symptoms from 3 to 40 years of age</li><ul> <li>Usually late childhood</li> </ul><li>Liver disease progresses from acute hepatitis to cirrhosis.</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Gene mutation</li><ul> <li>(1) Defective hepatocyte transport of copper into bile for excretion
<blockquote style="color: blue; ">Wilson's disease: ↓ incorporation copper into ceruloplasmin, ↓ excretion copper into bile</blockquote></li><li>(2) Defective incorporation of copper into ceruloplasmin (binding protein for copper in blood)</li> </ul><li>Unbound copper eventually accumulates in blood.</li><ul> <li>(1) Loosely attached to albumin</li><li>(2) Copper deposits in other tissues cause a toxic effect.</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Kayser-Fleischer ring (∼70%)
<blockquote style="color: blue; ">Kayser-Fleischer ring: excess copper in Descemet's membrane of cornea</blockquote></li><ul> <li>(1) Due to free copper deposits in Descemet's membrane in the cornea (<span>[[Fig. 18-12|Figure 18-12]]</span>)</li><li>(2) <i>Not</i> pathognomonic of Wilson's disease; can be seen in primary biliary cirrhosis</li> </ul><li>Central nervous system disease (>50%)</li><ul> <li>(1) Copper deposits in the putamen</li><ul> <li>Produces a movement disorder resembling parkinsonism</li> </ul><li>(2) Copper deposits in the subthalamic nucleus</li><ul> <li>Produces hemiballismus</li> </ul><li>(3) Copper is toxic to neurons in the cerebral cortex
<blockquote style="color: blue; ">Wilson's disease: lenticular degeneration in CNS; movement disorder; dementia</blockquote></li><ul> <li>Produces dementia</li> </ul> </ul><li>Hepatosplenomegaly (50%)</li><ul> <li>Liver biopsy shows increased copper.</li> </ul><li>Hemolytic anemia
<blockquote style="color: blue; ">Wilson's disease: hemolytic anemia; renal disease</blockquote></li><li>Renal disease</li><ul> <li>Proximal tubule damage produces Fanconi syndrome (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>).</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Decreased total serum copper</li><ul> <li>Due to decreased ceruloplasmin</li> </ul><li>Decreased serum ceruloplasmin
<blockquote style="color: blue; ">Wilson's disease: ↓ total serum copper, ceruloplasmin; ↓ serum/urine free copper</blockquote></li><ul> <li>Useful in diagnosing Wilson's disease in its early stages</li> </ul><li>Increased serum and urine free copper</li><ul> <li>Useful in diagnosing Wilson's disease in the later stages</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Penicillamine (copper chelator)
<blockquote style="color: blue; ">Rx Wilson's disease: penicillamine (copper chelator)</blockquote></li><li>Zinc</li><ul> <li>Inhibits copper reabsorption in intestine</li> </ul><li>Ammonium tetrathiomolybdate</li><ul> <li>(1) Competes for copper reabsorption in bowel</li><li>(2) Increases copper excretion in urine</li> </ul><li>Liver transplantation</li> </ol> </ol>
</div></html>
<html><a name="HC018044"></a> <br><a name="P018039"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal dominant (codominant)</li><li>Pathogenesis</li><ul> <li>(1) Alleles are inherited codominantly (each allele expresses itself).</li><li>(2) Normal allele is M (95% frequency in the United States).</li><ul> <li>MM is normal genotype with AAT in normal range.</li> </ul><li>(3) Deficient variant (decreased AAT) Z allele (1-2% frequency)
<blockquote style="color: blue; ">AAT deficiency: M is the normal allele; Z and S are deficiency variant alleles</blockquote></li><li>(4) Deficient variant (decreased AAT) S allele (2-3% frequency)</li><li>(5) Severe deficiency most commonly occurs in homozygous ZZ variant.</li><ul> <li>(a) Decreased (<15% of normal) AAT levels in serum</li><li>(b) Associated with panacinar emphysema (refer to <span macro="tag [[16 Upper and Lower Respiratory Disorders]] [[Chapter 16]]"></span>)</li><li>(c) Associated with cirrhosis of the liver (see later)</li> </ul><li>(6) Risk of lung disease in heterozygotes (e.g., MZ) is uncertain.</li> </ul><li>Most common cause of cirrhosis in children</li> </ol><li>Children with accumulation of AAT in hepatocytes</li><ol type="a"> <li>In ∼50% of homozygous ZZ patients, AAT is <i>not</i> secreted properly from hepatocytes.</li><li>Pathologic accumulation of AAT in hepatocytes causes liver damage.</li><ul> <li>Periodic acid-Schiff stains show red cytoplasmic granules (<span>[[Fig. 18-13|Figure 18-13]]</span>).</li> </ul><li>Presents as neonatal hepatitis with intrahepatic cholestasis
<blockquote style="color: blue; ">Cirrhosis in AAT deficiency: homozygous ZZ variant; AAT not secreted properly and accumulates in the liver</blockquote></li><li>Hepatitis progresses into cirrhosis.</li><ul> <li>AAT deficiency is the most common cause of cirrhosis in children.</li> </ul><li>Increased risk for hepatocellular carcinoma</li> </ol><li>Treatment for AAT deficiency</li><ol type="a"> <li>Pooled AAT given intravenously</li><li>Liver and lung transplantation</li> </ol> </ol>
</div></html>
<html><a name="HC018045"></a> <br><a name="P018040"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Cirrhosis: ↓ serum BUN, ↑ serum ammonia</blockquote>
<ol type="1"> <li>Decreased serum blood urea nitrogen (BUN) and increased serum ammonia</li><ul> <li>Due to disruption of the urea cycle</li> </ul><li>Fasting hypoglycemia
<blockquote style="color: blue; ">Hypoglycemia in cirrhosis: ↓ gluconeogenesis, ↓ glycogen stores</blockquote></li><ul> <li>Defective gluconeogenesis and decreased glycogen stores (see <span>[[Fig. 6-1|Figure 6-1]]</span>)</li> </ul><li>Chronic respiratory alkalosis</li><ul> <li>Toxic products from hepatic dysfunction overstimulate respiratory center (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li> </ul><li>Lactic acidosis
<blockquote style="color: blue; ">Cirrhosis: lactic acidosis, hyponatremia, hypokalemia</blockquote></li><ul> <li>Liver dysfunction in converting lactic acid to pyruvate (see <span>[[Fig. 6-1|Figure 6-1]]</span>)</li> </ul><li>Hyponatremia (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li><ol type="a"> <li>Decreased cardiac output</li><li>Kidney reabsorbs slightly hypotonic solution (↑ TBNa<sup>+</sup>/↑↑ TBW)</li> </ol><li>Hypokalemia</li><ul> <li>Secondary aldosteronism increases renal exchange of Na<sup>+</sup> for K<sup>+</sup> (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li> </ul><li>Increased PT</li><ul> <li>Decreased synthesis of coagulation factors</li> </ul><li>Hypoalbuminemia</li><ul> <li>Decreased synthesis of albumin
<blockquote style="color: blue; ">Severe liver dysfunction: ↓ serum albumin, ↑ PT</blockquote></li> </ul><li>Hypocalcemia</li><ol type="a"> <li>Hypoalbuminemia decreases the total serum calcium.
<blockquote style="color: blue; ">Hypocalcemia in cirrhosis: ↓ serum albumin, ↓ 25(OH)-vitamin D</blockquote></li><ul> <li>Approximately 40% of the total calcium is calcium bound to albumin.</li> </ul><li>Vitamin D deficiency</li><ul> <li>Decreased liver 25-hydroxylation of vitamin D.</li> </ul> </ol><li>Mild transaminasemia</li><ul> <li>Enzymes are <i>not</i> markedly increased due to the loss of parenchymal cells.</li> </ul> </ol>
</div></html>
<html><a name="HC018047"></a> <br><a name="P018048"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Tumor-like condition</li><li>More common in women than men</li><li>Cause is unknown</li><ul> <li>Probable reaction to injury</li> </ul><li>Usually an incidental finding</li> </ol><li>Gross findings</li><ol type="a"> <li>Poorly encapsulated nodule</li><li>Central depressed stellate scar
<blockquote style="color: blue; ">FNH: central stellate scar with radiating fibrous septae</blockquote></li><ul> <li>Contains large blood vessels</li> </ul><li>Fibrous septae radiate to the periphery.</li> </ol><li>CT scan</li><ul> <li>Hypervascular mass with arteriovenous connections</li> </ul><li>Treatment</li><ul> <li>Leave it alone unless associated with pain</li> </ul> </ol>
</div></html>
<html><a name="HC018048"></a> <br><a name="P018049"></a><div class="PA" style="color: black; "><ol type="1"> <li>Cavernous hemangioma
<blockquote style="color: blue; ">Cavernous hemangioma: most common benign tumor; potential for intraperitoneal hemorrhage</blockquote></li><ol type="a"> <li>Most common benign tumor</li><li>Best diagnosed with enhanced CT scan</li><li>Rare cause of intraperitoneal hemorrhage</li> </ol><li>Liver (hepatic) cell adenoma</li><ol type="a"> <li>Benign tumor of hepatocytes</li><li>Occurs in women more often than men</li><li>Causes</li><ul> <li>(1) OCPs (most common)</li><li>(2) Anabolic steroids</li><li>(3) Von Gierke's glycogenosis</li> </ul><li>Highly vascular tumors
<blockquote style="color: blue; ">Liver cell adenoma: OCPs; intraperitoneal hemorrhage</blockquote></li><ul> <li>(1) Tendency to rupture during pregnancy</li><li>(2) Produce intraperitoneal hemorrhage</li> </ul><li>Tend to regress if off OCP and anabolics</li> </ol><li>Treatment is surgery if symptomatic.</li> </ol>
</div></html>
<html><a name="HC018049"></a> <br><a name="P018050"></a><div class="PA" style="color: black; "><ol type="1"> <li>Metastasis</li><ol type="a"> <li>Most common liver cancer (see <span>[[Fig. 8-2E|Figure 8-2]]</span>)</li><li>Primary cancers of lung (most common), gastrointestinal tract, breast
<blockquote style="color: blue; ">Metastasis: most common liver cancer; lung most common primary site</blockquote></li><li>Multiple nodular masses</li> </ol><li>Hepatocellular carcinoma (HCC)</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Most common primary liver cancer</li><li>(2) Rapidly increasing in the United States due to increase in HCV infection</li><li>(3) Occurs in males more than females</li><ul> <li>Peaks around fifth and sixth decades</li> </ul><li>(4) Causes</li><ul> <li>(a) Postnecrotic cirrhosis due to chronic HBV and HCV
<blockquote style="color: blue; ">HCC: pre-existing HBV or HCV cirrhosis most common risk factor</blockquote></li><li>(b) Alcoholic cirrhosis</li><li>(c) Aflatoxins (from <i>Aspergillus</i> mold in grains and peanuts)</li><li>(d) Hereditary hemochromatosis, Wilson's disease</li><li>(e) PBC, AAT deficiency, tyrosinemia</li> </ul> </ul><li>Pathogenesis</li><ul> <li>(1) Most often associated with pre-existing cirrhosis
<blockquote style="color: blue; ">HCC: pre-existing cirrhosis</blockquote></li><li>(2) Postnecrotic cirrhosis HBV/HCV most common risk factors</li> </ul><li>Gross findings</li><ul> <li>(1) Focal, multifocal, or diffusely infiltrating cancer (<span>[[Fig. 18-14|Figure 18-14]]</span>)</li><ul> <li>With or without pre-existing cirrhosis (usually with pre-existing cirrhosis)</li> </ul><li>(2) Portal and hepatic vein invasion is common.</li> </ul><li>Microscopic findings
<blockquote style="color: blue; ">HCC: bile in neoplastic cells</blockquote></li><ul> <li>Characteristic finding is the presence of bile in neoplastic cells.</li> </ul><li>Clinical findings</li><ul> <li>(1) Over one third are asymptomatic.</li><li>(2) Abdominal pain is a common initial presentation.</li><li>(3) Fever</li><ul> <li>Due to liver cell necrosis</li> </ul><li>(4) Rapid enlargement of the liver in a patient with cirrhosis
<blockquote style="color: blue; ">HCC: pain; ↑ in ascites, fever, blood in ascitic fluid</blockquote></li><ul> <li>Increased ascites; blood present in ascitic fluid</li> </ul> </ul><li>Laboratory findings
<blockquote style="color: blue; ">HCC: ↑ serum AFP; rapidly increasing bloody ascites</blockquote></li><ul> <li>(1) Increased α-fetoprotein (AFP; 70%)</li><ul> <li>Sensitivity 40% to 60%, specificity 80% to 94%</li> </ul><li>(2) Increased serum ALP and GGT</li><ul> <li>Sudden increase is a characteristic finding.</li> </ul><li>(3) Production of ectopic hormones
<blockquote style="color: blue; ">Ectopic hormones: PTH-related protein, insulin-like factor; EPO</blockquote></li><ul> <li>(a) Erythropoietin (EPO; secondary polycythemia)</li><li>(b) Insulin-like factor (hypoglycemia)</li><li>(c) Parathyroid hormone (PTH)-related protein (hypercalcemia)</li> </ul> </ul><li>Lung most common metastatic site</li><li>Diagnosis</li><ul> <li>(1) CT scan and ultrasound localize HCC.</li><li>(2) Angiography shows pooling and increased vascularity.</li> </ul><li>Treatment</li><ul> <li>(1) Surgery (<20% are surgical candidates)</li><li>(2) Liver transplantation</li><li>(3) Radiation and chemotherapy are usually not helpful.</li> </ul><li>Prognosis</li><ul> <li>(1) If unresectable, most die within 6 months.</li><li>(2) If resectable, 5-year survival rate is 30% to 50%.
<blockquote style="color: blue; ">Liver angiosarcoma: exposure to vinyl chloride (plastic pipes)</blockquote></li> </ul> </ol><li>Angiosarcoma</li><ul> <li>Exposure to vinyl chloride (most common cause), arsenic, or thorium dioxide</li> </ul> </ol>
</div></html>
![[18.VIII.A.Focal nodular hyperplasia (FNH)]]
<<tiddler [[18.VIII.A.Focal nodular hyperplasia (FNH)]]>>
![[18.VIII.B.Benign tumors]]
<<tiddler [[18.VIII.B.Benign tumors]]>>
![[18.VIII.C.Malignant tumors]]
<<tiddler [[18.VIII.C.Malignant tumors]]>>
<html><a name="HC018060"></a> <br><a name="P018063"></a><div class="PA" style="color: black; "><ol type="1"> <li>Annular pancreas</li><ol type="a"> <li>Dorsal and ventral buds form a ring around the duodenum.</li><li>Associated with small bowel obstruction</li> </ol><li>Aberrant pancreatic tissue (i.e., heterotopic rest, choristoma)</li><ul> <li>Locations-wall of stomach, duodenum, jejunum, or Meckel diverticulum</li> </ul><li>Major pancreatic duct
<blockquote style="color: blue; ">Major pancreatic duct: empties into terminal part of CBD; stone blocking CBD causes acute pancreatitis</blockquote></li><ol type="a"> <li>Major pancreatic duct and CBD are confluent in their terminal part.</li><ul> <li>Both empty their contents into the duodenum via the ampulla of Vater.</li> </ul><li>Important in the pathogenesis of acute pancreatitis</li><ul> <li>(1) Stone(s) obstruct terminal part of the CBD →</li><li>(2) Increased back-pressure refluxes bile into the major pancreatic duct →</li><li>(3) Bile activates pancreatic proenzymes causing acute pancreatitis</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC018061"></a> <br><a name="PB018011"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Third space fluid</b> is sequestered fluid that is unavailable for maintenance of volume in the vascular compartment (nonfunctional extracellular fluid). In acute pancreatitis, it refers to the peripancreatic collection of fluid that commonly occurs as the pancreas autodigests itself. If conditions improve, the third space fluid gains entry back into the vascular compartment and may cause fluid overload.
<blockquote style="color: blue; ">Third space fluid: fluid unavailable for maintenance of volume in vascular compartment</blockquote></div><a name="PB018012"></a><div class="BB" style="color: rgb(47, 79, 79); ">Admission (first 24 hours): age > 55 years old, WBC count > 16,000 cells/mm<sup>3</sup>, serum glucose > 200 mg/dL, serum LDH > 350 IU/L, serum AST > 250 U/L. Subsequent 48 hours: hematocrit drop > 10% with hydration, serum BUN rise > 5 mg/dL, Pa<span style="font-variant:small-caps;">o</span><sub>2</sub> < 60 mm Hg (respiratory failure), base deficit > 4 mEq/L (metabolic acidosis), calcium < 8 mg/dL, fluid sequestration > 6 L. Prognosis: <3 signs = 0.9% mortality rate; 3-4 signs = 11% to 16% mortality rate; 5-6 signs = 33 to 40% mortality rate; >6 signs = 100% mortality rate.</div><a name="P018064"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>Alcohol abuse and gallstones are the major causes.
<blockquote style="color: blue; ">Alcohol abuse: most common cause of acute pancreatitis</blockquote></li><li>Must be activation of pancreatic proenzymes (inactive enzymes)</li><ul> <li>Activation leads to autodigestion of the pancreas.</li> </ul><li>Mechanisms of activation of proenzymes</li><ul> <li>(1) Obstruction of the main pancreatic duct or terminal CBD</li><ul> <li>(a) Gallstones (see section IX)</li><li>(b) Alcohol thickens ductal secretions.</li><ul> <li>Also increases duct permeability to enzymes</li> </ul> </ul><li>(2) Chemical injury of acinar cells</li><ul> <li>Examples-thiazides, alcohol, triglyceride (>1000 mg/dL)</li> </ul><li>(3) Infectious injury of acinar cells</li><ul> <li>Examples-CMV, mumps, coxsackievirus</li> </ul><li>(4) Mechanical injury of acinar cells</li><ul> <li>Examples-seat belt trauma, posterior penetration of duodenal ulcer
<blockquote style="color: blue; ">Seat belt trauma: most common cause of pancreatitis in children</blockquote></li> </ul><li>(5) Metabolic activation of proenzymes (e.g., hypercalcemia, ischemia, shock)</li> </ul><li>Trypsin is important in the activation of proenzymes.</li><ul> <li>(1) Proteases damage acinar cell structure.</li><li>(2) Lipases and phospholipases produce enzymatic fat necrosis.</li><li>(3) Elastases damage vessel walls and produce hemorrhage (see <span>[[Fig. 1-11H|Figure 1-11]]</span>).</li><li>(4) Activated enzymes also circulate in the blood.</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Fever, nausea, and vomiting</li><li>Severe, boring (knife-like) midepigastric pain with radiation into the back
<blockquote style="color: blue; ">Pancreatitis: pain radiates into the back; described as a knife-like pain</blockquote></li><ul> <li>Radiation into back is due to its retroperitoneal location.</li> </ul><li>Hypovolemic shock</li><ul> <li>Due to third space loss of fluids</li> </ul><li>Hypoxemia
<blockquote style="color: blue; ">Hypoxemia: circulating phospholipase destroys surfactant</blockquote></li><ul> <li>(1) Circulating pancreatic phospholipase destroys surfactant.</li><ul> <li>Loss of surfactant produces atelectasis and intrapulmonary shunting.</li> </ul><li>(2) Acute respiratory distress syndrome (ARDS) may occur.</li> </ul><li>Grey-Turner sign (flank hemorrhage; <span>[[Fig. 18-18|Figure 18-18]]</span>)
<blockquote style="color: blue; ">Grey-Turner sign: flank hemorrhage</blockquote></li><li>Cullen's sign (periumbilical hemorrhage; <span>[[Fig. 18-19|Figure 18-19]]</span>)</li><li>Disseminated intravascular coagulation
<blockquote style="color: blue; ">Cullen's sign: perium- bilical hemorrhage</blockquote></li><ul> <li>Due to activation of prothrombin by trypsin</li> </ul><li>Tetany</li><ul> <li>(1) Hypocalcemia is caused by enzymatic fat necrosis.</li><li>(2) Calcium binds to fatty acids leading to a decrease in ionized calcium.</li> </ul> </ol><li>Complications</li><ol type="a"> <li>Pancreatic necrosis</li><ul> <li>(1) Systemic signs occur earlier than usual.</li><li>(2) Higher fever than usual; sinus tachycardia</li><li>(3) Greater degree of neutrophilic leukocytosis</li><li>(4) Peripancreatic infections occur in 40% to 70% of cases.</li> </ul><li>Pancreatic pseudocyst (20%)</li><ul> <li>(1) Collection of digested pancreatic tissue around pancreas</li><li>(2) Abdominal mass with persistence of serum amylase longer than 10 days</li><ul> <li>Amount of amylase in the fluid surpasses renal clearance of amylase.
<blockquote style="color: blue; ">Persistent increase in serum amylase: consider pancreatic pseudocyst</blockquote></li> </ul><li>(3) Treatment</li><ul> <li>(a) If <5 cm, observe and follow with CT scan.</li><ul> <li>Most resolve without surgical intervention.</li> </ul><li>(b) If >5 cm, percutaneous drainage with CT or ultrasound guidance</li> </ul> </ul><li>Pancreatic abscess</li><ul> <li>(1) Clinical and laboratory findings</li><ul> <li>(a) Abdominal pain</li><li>(b) High fever due to sepsis</li><ul> <li>Usually gram-negative infections such as <i>E. coli</i> or <i>Pseudomonas</i> spp.</li> </ul><li>(c) Neutrophilic leukocytosis</li><li>(d) Persistent hyperamylasemia
<blockquote style="color: blue; ">Pancreatic abscess: higher fever from gram-negative sepsis; ↑ amylase; CT shows bubbles</blockquote></li> </ul><li>(2) Diagnosis</li><ul> <li>(a) CT scan shows multiple radiolucent bubbles in the retroperitoneum.</li><li>(b) CT-guided aspiration of abscess identifies organisms.</li> </ul><li>(3) Treatment</li><ul> <li>(a) Surgical drainage</li><li>(b) Imipenem-cilastin</li> </ul> </ul><li>Pancreatic ascites
<blockquote style="color: blue; ">Pancreatic ascites: leaking pseudocyst</blockquote></li><ul> <li>(1) Usually caused by leaking of a pseudocyst</li><li>(2) Peritoneal fluid has high amylase level.</li><li>(3) Usually resolves spontaneously</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Serum amylase</li><ul> <li>(1) <i>Not</i> specific for pancreatitis</li><li>(2) Also present in salivary glands
<blockquote style="color: blue; ">Amylase: not specific for pancreatitis</blockquote></li><ul> <li>Increased in mumps</li> </ul><li>(3) Amylase in acute pancreatitis</li><ul> <li>(a) Sensitivity 85%, specificity 70%</li><li>(b) Initial increase at 2 to 12 hours; peaks over 12 to 30 hours; returns to normal in 2 to 4 days</li><ul> <li>Increased renal clearance
<blockquote style="color: blue; ">Acute pancreatitis: increased clearance of amylase in urine</blockquote></li> </ul><li>(c) Present in urine for 1 to 14 days</li><li>(d) Persistent increase in serum amylase > 7 days</li><ul> <li>Suggests pancreatic pseudocyst; collection of amylase-rich fluid around pancreas</li> </ul><li>(e) Urine amylase</li><ul> <li>Initial increase over 4 to 8 hours; peaks at 18 to 36 hours; returns to normal over 7 to 10 days</li> </ul> </ul><li>(4) Amylase in chronic pancreatitis</li><ul> <li>(a) Less reliable than in acute disease</li><li>(b) Values either normal, borderline, or slightly increased</li> </ul> </ul><li>Serum lipase</li><ul> <li>(1) More specific for pancreatitis</li><ul> <li>Is <i>not</i> excreted in urine</li> </ul><li>(2) Lipase in acute pancreatitis</li><ul> <li>(a) Sensitivity 80%, specificity 75%
<blockquote style="color: blue; ">Serum lipase: more specific and lasts longer than amylase in acute pancreatitis; excellent screen for acute pancreatitis</blockquote></li><li>(b) Initial increase in 3 to 6 hours; peaks in 12 to 30 hours; returns to normal over 7 to 14 days</li> </ul><li>(3) Lipase in chronic pancreatitis</li><ul> <li><i>Not</i> clinically useful</li> </ul> </ul><li>Serum immunoreactive trypsin</li><ul> <li>(1) Trypsin is specific for the pancreas.</li><li>(2) Excellent newborn screen for cystic fibrosis</li><li>(3) Serum immunoreactive trypsin in acute pancreatitis
<blockquote style="color: blue; ">Serum immunoreactive trypsin: excellent newborn screen for cystic fibrosis</blockquote></li><ul> <li>(a) Sensitivity 95% to 100%</li><li>(b) Increases 5 to 10 times normal</li><li>(c) Remains increased for 4 to 5 days</li> </ul><li>(4) Serum immunoreactive trypsin in chronic pancreatitis</li><ul> <li>Decreased concentration</li> </ul> </ul><li>Neutrophilic leukocytosis</li><li>Hypocalcemia, hyperglycemia (destruction of β-islet cells)</li> </ol><li>Imaging studies</li><ol type="a"> <li>CT scan is the gold standard for pancreatic imaging.
<blockquote style="color: blue; ">CT scan: gold standard for pancreatic imaging</blockquote></li><li>Plain abdominal radiograph</li><ul> <li>(1) Sentinel loop in subjacent duodenum or transverse colon (cut-off sign)</li><ul> <li>Localized ileus, where the bowel does <i>not</i> demonstrate peristalsis</li> </ul><li>(2) Left-sided pleural effusion containing amylase (10% of cases)</li> </ul> </ol><li>Ranson criteria are used to determine prognosis in acute pancreatitis.
<blockquote style="color: blue; ">Plain radiograph: sentinel loop; left-sided pleural effusion</blockquote></li><li>Treatment</li><ol type="a"> <li>NPO until clinically improved</li><li>Crystalloid solutions</li><li>Meperidine or fentanyl for pain</li><li>Nasogastric suction if vomiting severe</li><li>Oxygen</li> </ol> </ol>
</div></html>
<html><a name="HC018062"></a> <br><a name="P018065"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Occurs in men more commonly than women</li><li>Majority are idiopathic.
<blockquote style="color: blue; ">Chronic pancreatitis adults: alcohol abuse most common known cause</blockquote></li><li>Known causes</li><ul> <li>(1) Alcohol abuse is the most common known cause.</li><li>(2) Cystic fibrosis is the most common cause in children.</li><li>(3) Malnutrition is the most common cause in developing countries.
<blockquote style="color: blue; ">Chronic pancreatitis in children: cystic fibrosis most common cause</blockquote></li><li>(4) Autoimmune</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Repeated attacks of acute pancreatitis produce duct obstruction.
<blockquote style="color: blue; ">Chronic pancreatitis in developing countries: malnutrition</blockquote></li><li>Calcified concretions occur as well as dilation of the ducts.</li><ul> <li>Radiographic dyes show a "chain of lakes" appearance in the major duct.</li> </ul> </ol><li>Clinical findings
<blockquote style="color: blue; ">Chronic pancreatitis: dyes show "chain of lakes" in major duct</blockquote></li><ol type="a"> <li>Severe pain radiating into the back</li><li>Malabsorption</li><ul> <li>Indicates >90% exocrine function destroyed</li> </ul><li>Type 1 diabetes mellitus (70%)
<blockquote style="color: blue; ">Chronic pancreatitis: malabsorption, type 1 diabetes mellitus</blockquote></li><ul> <li>Brittle diabetes due to loss of insulin and glucagon</li> </ul><li>Pancreatic pseudocyst</li> </ol><li>Laboratory and radiographic findings</li><ol type="a"> <li>Increased amylase and lipase (neither are reliable)</li><li>Increased serum immunoreactive trypsin</li><li>Tests for pancreatic insufficiency
<blockquote style="color: blue; ">Chronic pancreatitis: CT scan dystrophic calcification</blockquote></li><ul> <li>(1) CT scan of pancreas shows dystrophic calcification (see <span>[[Fig. 1-9|Figure 1-9]]</span>).</li><ul> <li>Sign of chronic pancreatitis</li> </ul><li>(2) Functional tests</li><ul> <li>(a) Secretin stimulation test (requires instrumentation)</li><ul> <li>Tests ability of pancreas to secrete fluids and electrolytes
<blockquote style="color: blue; ">Tests pancreatic insufficiency: secretin stimulation; bentiromide</blockquote></li> </ul><li>(b) Bentiromide test</li><ul> <li>Tests ability of pancreatic chymotrypsin to cleave orally administered bentiromide to para-aminobenzoic acid (measured in urine)</li> </ul> </ul> </ul> </ol><li>Treatment</li><ol type="a"> <li>Abstain from alcohol.</li><li>Addiction is common.</li><ul> <li>Try simple analgesics or NSAIDs</li> </ul><li>Pancreatic enzymes</li><li>Fat-soluble vitamins</li><li>Octreotide for pain if idiopathic</li> </ol><li>Approximately 50% of patients die within 10 years.</li> </ol>
</div></html>
<html><a name="HC018063"></a> <br><a name="PB018013"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Whipple's procedure</b> is an en bloc resection of the pancreatic head and neck (distal pancreas remains to prevent diabetes mellitus) and resection of part of the CBD. In some cases, there is resection of the antrum with vagotomy.</div><a name="P018066"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Slightly more common in men than women</li><li>Incidence rate is stable in men and women.</li><li>Usually occurs in seventh and eighth decades of life</li><li>Adenocarcinoma with varying degrees of differentiation</li><li>Causes</li><ul> <li>(1) Smoking (most common cause)</li><ul> <li>Includes smokeless tobacco
<blockquote style="color: blue; ">Pancreatic carcinoma: smoking most common cause; chronic pancreatitis</blockquote></li> </ul><li>(2) Chronic pancreatitis</li><li>(3) Hereditary pancreatitis</li><li>(4) Diabetes mellitus</li><ul> <li>Particularly in women</li> </ul><li>(5) High saturated fat diet; obesity; cirrhosis</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Association with <i>K-RAS</i> gene mutation</li><li>Mutation of suppressor genes (<i>TP16</i> and <i>TP53</i>)</li> </ol><li>Location</li><ol type="a"> <li>Most occur in the pancreatic head (65% of cases) (<span>[[Fig. 18-20|Figure 18-20]]</span>)</li><ul> <li>Often blocks CBD causing jaundice</li> </ul><li>Remainder occur in the body and tail.</li> </ol><li>Clinical and laboratory findings
<blockquote style="color: blue; ">Carcinoma in head of pancreas: jaundice, light-colored stools, palpable gallbladder</blockquote></li><ol type="a"> <li>Epigastric pain with weight loss (>90%)</li><li>Signs of CBD obstruction (carcinoma of head of pancreas)</li><ul> <li>(1) Jaundice (>90%; CB > 50%)</li><li>(2) Light-colored stools (absent UBG)</li><li>(3) Palpable gallbladder (Courvoisier's sign; 30%)</li> </ul><li>Superficial migratory thrombophlebitis (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>)</li><li>Metastasis to left supraclavicular node (Virchow's node)
<blockquote style="color: blue; ">Pancreatic cancer: metastasis left supraclavicular node</blockquote></li><ul> <li>Also occurs in stomach cancer</li> </ul><li>Periumbilical metastasis (Sister Mary Joseph's sign)</li><ul> <li>Also occurs in stomach cancer
<blockquote style="color: blue; ">Pancreatic cancer: CA19-9 gold standard tumor marker</blockquote></li> </ul><li>Increased CA19-9</li><ul> <li>Gold standard tumor marker</li> </ul> </ol><li>Diagnosis
<blockquote style="color: blue; ">Pancreas carcinoma: CT scan best test</blockquote></li><ol type="a"> <li>Helical CT scan is best test.</li><ul> <li>(1) Shows C sign in cancer of head of pancreas</li><ul> <li>Cancer indents duodenum; looks like the letter C</li> </ul><li>(2) CT guided percutaneous biopsy for diagnosis</li> </ul> </ol><li>Treatment</li><ul> <li>Surgery (Whipple's procedure), radiation, chemotherapy</li> </ul><li>Five-year survival rate is 20%.</li> </ol>
</div></html>
![[18.X.A.Embryologic abnormalities of the pancreas]]
<<tiddler [[18.X.A.Embryologic abnormalities of the pancreas]]>>
![[18.X.B.Acute pancreatitis]]
<<tiddler [[18.X.B.Acute pancreatitis]]>>
![[18.X.C.Chronic pancreatitis]]
<<tiddler [[18.X.C.Chronic pancreatitis]]>>
![[18.X.D.Exocrine pancreatic cancer]]
<<tiddler [[18.X.D.Exocrine pancreatic cancer]]>>
<html><a name="HC019002"></a> <br><a name="P019001"></a><div class="PA" style="color: black; "><ul> <li>Examples-urea, creatinine, uric acid</li> </ul>
</div></html>
<html><a name="HC019003"></a><span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span> <br> <br><a name="P019002"></a><div class="PA" style="color: black; "><ul> <li>Controls the synthesis and excretion of bicarbonate and hydrogen ions</li> </ul>
</div></html>
<html><a name="HC019004"></a> <br><a name="P019003"></a><div class="PA" style="color: black; "><ul> <li>Examples-sodium, glucose, amino acids</li> </ul>
</div></html>
<html><a name="HC019005"></a><span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span> <br> <br><a name="P019004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Controls water by concentrating and diluting urine</li><li>Controls sodium reabsorption in the proximal and distal collecting tubules</li> </ol>
</div></html>
<html><a name="HC019006"></a><span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span> <br> <br><a name="P019005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Angiotensin II (ATII)</li><ol type="a"> <li>Vasoconstricts peripheral resistance arterioles and efferent arterioles</li><li>Stimulates the synthesis and release of aldosterone</li> </ol><li>Renal-derived prostaglandin (PGE<sub>2</sub>)</li><ul> <li>Vasodilates the afferent arterioles</li> </ul> </ol>
</div></html>
<html><a name="HC019007"></a><span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span> <br> <br><a name="P019006"></a><div class="PA" style="color: black; "><ul> <li>Synthesized in the renal cortex by interstitial cells in peritubular capillary bed</li> </ul>
</div></html>
<html><a name="HC019008"></a><span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span> <br> <br><a name="PB019001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Vitamin D</b> promotes bone mineralization by stimulating the release of alkaline phosphatase from osteoblasts. Alkaline phosphatase hydrolyzes pyrophosphate and other inhibitors of calcium-phosphate crystallization.
<blockquote style="color: blue; ">Renal stone: most common upper urinary tract cause of hematuria</blockquote></div><a name="P019007"></a><div class="PA" style="color: black; "><ol type="1"> <li>Second hydroxylation of vitamin D
<blockquote style="color: blue; ">Second hydroxylation of vitamin D: 1-α-hydroxylase in proximal tubule</blockquote></li><ol type="a"> <li>1-α-Hydroxylase is synthesized in the proximal renal tubule cells.</li><li>Converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol.</li> </ol><li>Functions of vitamin D</li><ol type="a"> <li>Increases gastrointestinal reabsorption of calcium and phosphorus</li><li>Promotes bone mineralization; maintains serum calcium level</li><li>Increases monocytic stem cells to become osteoclasts</li> </ol> </ol>
</div></html>
![[19.I.A.Excretes harmful waste products]]
<<tiddler [[19.I.A.Excretes harmful waste products]]>>
![[19.I.B.Maintains acid-base homeostasis (refer to Chapter 4)]]
<<tiddler [[19.I.B.Maintains acid-base homeostasis (refer to Chapter 4)]]>>
![[19.I.C.Reabsorbs essential substances]]
<<tiddler [[19.I.C.Reabsorbs essential substances]]>>
![[19.I.D.Regulates water and sodium metabolism (refer to Chapter 4)]]
<<tiddler [[19.I.D.Regulates water and sodium metabolism (refer to Chapter 4)]]>>
![[19.I.E.Maintains vascular tone (refer to Chapter 4)]]
<<tiddler [[19.I.E.Maintains vascular tone (refer to Chapter 4)]]>>
![[19.I.F.Produces erythropoietin (refer to Chapter 11)]]
<<tiddler [[19.I.F.Produces erythropoietin (refer to Chapter 11)]]>>
![[19.I.G.Maintains calcium homeostasis (refer to Chapter 22)]]
<<tiddler [[19.I.G.Maintains calcium homeostasis (refer to Chapter 22)]]>>
<html><a name="HC019010"></a> <br><a name="P019008"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Infection: most common cause of lower urinary tract hematuria</blockquote>
<ol type="1"> <li>Upper urinary tract (kidneys, ureter) causes of hematuria</li><ol type="a"> <li>Renal stone</li><li>Glomerulonephritis
<blockquote style="color: blue; ">Transitional cell carcinoma bladder: most common noninfectious cause of lower urinary tract hematuria</blockquote></li><ul> <li>Characterized by dysmorphic RBCs (irregular membrane)</li> </ul><li>Renal cell carcinoma</li> </ol><li>Lower urinary tract (bladder, urethra, prostate) causes of hematuria</li><ol type="a"> <li>Infection</li><li>Transitional cell carcinoma
<blockquote style="color: blue; ">Benign prostatic hyperplasia: most common cause of microscopic hematuria in adult males</blockquote></li><ul> <li>Most common cause of gross hematuria in the absence of infection</li> </ul><li>Benign prostatic hyperplasia</li><ul> <li>Most common cause of microscopic hematuria in adult males</li> </ul> </ol><li>Drugs associated with hematuria</li><ol type="a"> <li>Anticoagulants (warfarin, heparin)</li><li>Cyclophosphamide
<blockquote style="color: blue; ">Anticoagulants: most common drugs causing hematuria</blockquote></li><ul> <li>(1) Hemorrhagic cystitis</li><li>(2) Risk factor for transitional cell carcinoma</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC019011"></a> <br><a name="P019009"></a><div class="PA" style="color: black; "><ol type="1"> <li>General</li><ol type="a"> <li>Protein > 150 mg/24 hours or >30 mg/dL (dipstick)</li><li>Persistent proteinuria usually indicates renal disease.
<blockquote style="color: blue; ">Persistent proteinuria: usually indicates intrinsic renal disease</blockquote></li><li>Qualitative tests include dipsticks and sulfosalicylic acid (SSA).</li><ul> <li>(1) Dipsticks are specific for albumin.</li><li>(2) SSA detects albumin and globulins.</li> </ul><li>Quantitative test is a 24-hour urine collection.</li> </ol><li>Types of proteinuria (<span>[[Table 19-1|Table 19-1. TYPES OF PROTEINURIA]]</span>)</li> </ol>
</div></html>
![[19.II.A.Hematuria]]
<<tiddler [[19.II.A.Hematuria]]>>
![[19.II.B.Proteinuria]]
<<tiddler [[19.II.B.Proteinuria]]>>
<html><a name="HC019013"></a> <br><a name="P019010"></a><div class="PA" style="color: black; "><ul> <li>Normal serum BUN is 7 to 18 mg/dL.</li><ol type="1"> <li>End-product of amino acid and pyrimidine metabolism</li><ul> <li>Produced by the liver urea cycle</li><ol type="a"> <li>Filtered in the kidneys</li><ul> <li>(1) Partly reabsorbed in the proximal tubule</li><li>(2) Amount reabsorbed is flow dependent.</li><ul> <li>(a) Decreased glomerular filtration rate, more reabsorbed</li><li>(b) Increased glomerular filtration rate, less reabsorbed</li> </ul> </ul><li>Extrarenal loss with very high serum concentration
<blockquote style="color: blue; ">Urea: some extrarenal loss (e.g., skin) with high serum concentration</blockquote></li><li>Serum levels depend on the following:</li><ul> <li>(1) Glomerular filtration rate (GFR)</li><li>(2) Protein content in the diet</li><li>(3) Proximal tubule reabsorption
<blockquote style="color: blue; ">Congestive heart failure: most common cause of increased serum BUN</blockquote></li><li>(4) Functional status of the urea cycle</li> </ul> </ol> </ul><li>Causes of increased and decreased serum BUN (<span>[[Table 19-2|Table 19-2. CAUSES OF INCREASED AND DECREASED SERUM BUN]]</span>)</li> </ol> </ul>
</div></html>
<html><a name="HC019014"></a> <br><a name="P019011"></a><div class="PA" style="color: black; "><ul> <li>Normal serum creatinine is 0.6 to 1.2 mg/dL.</li><ol type="1"> <li>Metabolic end-product of creatine in muscle</li><ul> <li>Creatine binds phosphate in muscle for ATP synthesis.
<blockquote style="color: blue; ">Creatinine: end-product of creatine metabolism Creatinine: filtered; not reabsorbed or secreted</blockquote></li> </ul><li>Creatinine is filtered in the kidneys and <i>not</i> reabsorbed or secreted.</li><ul> <li>Excellent metabolite for renal clearance testing</li> </ul><li>Serum concentration varies with age and muscle mass.</li><ul> <li>Increased with age, decreased in muscle wasting</li> </ul><li>Increase in serum BUN and creatinine is called azotemia.</li><li>Causes of increased and decreased serum creatinine
<blockquote style="color: blue; ">Creatine supplements: ↑ serum creatinine</blockquote></li><ul> <li>Similar to those for serum BUN</li> </ul> </ol> </ul>
</div></html>
<html><a name="HC019015"></a> <br><a name="P019012"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Azotemia: ↑ serum BUN and creatinine</blockquote>
<ol type="1"> <li>Using normal values, the normal ratio is 15 (<span>[[Fig. 19-1A|Figure 19-1]]</span>).</li><ol type="a"> <li>Creatinine is filtered and is neither reabsorbed nor secreted.</li><li>Urea is filtered and partly reabsorbed in the proximal tubule.
<blockquote style="color: blue; ">Urea: filtered; partly reabsorbed</blockquote></li><li>BUN:Cr ratio depends on changes at several times:</li><ul> <li>(1) Before the kidneys (prerenal)</li><li>(2) Within the kidney parenchyma (renal)</li><li>(3) After the kidneys (postrenal)</li> </ul> </ol><li>Prerenal, renal, and postrenal azotemia</li><ol type="a"> <li>Azotemia refers to an increase in serum BUN and creatinine.</li><li>Prerenal azotemia</li><ul> <li>(1) Caused by a decrease in cardiac output</li><ul> <li>(a) Hypoperfusion of the kidneys decreases GFR.</li><li>(b) There is <i>no</i> intrinsic renal parenchymal disease.</li> </ul><li>(2) Examples-blood loss, congestive heart failure</li><li>(3) Serum BUN:Cr ratio > 15 (<span>[[Fig. 19-1B|Figure 19-1]]</span>)
<blockquote style="color: blue; ">Prerenal azotemia: ↓ cardiac output, ↓ GFR; ratio > 15</blockquote></li><ul> <li>(a) Decreased GFR causes creatinine and urea to back up in blood.</li><ul> <li>Ratio remains unchanged, because of proportionate increase.</li> </ul><li>(b) After filtration, proportionately more urea is reabsorbed back into the blood due to the decreased flow rate (P<sub>O</sub> > P<sub>H</sub>; refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>).</li><ul> <li>All of the creatinine is excreted in the urine.</li> </ul><li>(c) Addition of proportionately more urea to blood increases the ratio to >15.</li><li>(d) Example-serum BUN 80 mg/dL, serum creatinine 4 mg/dL</li><ul> <li>BUN:Cr ratio is 20.</li> </ul> </ul> </ul><li>Renal azotemia (uremia)</li><ul> <li>(1) Caused by parenchymal damage to the kidneys</li><li>(2) Examples-acute tubular necrosis, chronic renal failure</li><li>(3) Serum BUN:Cr ratio ≤15 (<span>[[Fig. 19-1C|Figure 19-1]]</span>).
<blockquote style="color: blue; ">Renal azotemia: intrinsic renal disease; extrarenal loss of urea; ratio ≤ 15</blockquote></li><ul> <li>(a) Decreased GFR causes creatinine and urea to back up in blood; increased extrarenal loss of urea</li><ul> <li>Ratio is already <15 due to extrarenal loss of urea</li> </ul><li>(b) After filtration, both urea and creatinine are lost in the urine.</li><ul> <li>Proximal tubule cells are sloughed off in renal failure.</li> </ul><li>(c) Serum BUN:Cr ratio remains ≤15.</li><li>(d) Example-serum BUN 80 mg/dL, serum creatinine 8 mg/dL</li><ul> <li>BUN:Cr ratio is 10.</li> </ul> </ul> </ul><li>Postrenal azotemia</li><ul> <li>(1) Caused by urinary tract obstruction below the kidneys</li><ul> <li><i>No</i> intrinsic parenchymal disease</li> </ul><li>(2) Examples-prostate hyperplasia; blockage of ureters by stones/cancer</li><li>(3) Serum BUN:Cr ratio > 15 (<span>[[Fig. 19-1D|Figure 19-1]]</span>)</li><ul> <li>(a) Obstruction to urine flow decreases the GFR.</li><li>(b) Backup of urea and creatinine in the blood</li><ul> <li>Proportionate increase at this point; ratio unchanged</li> </ul><li>(c) Increased tubular pressure causes back-diffusion of urea (<i>not</i> creatinine) into blood.
<blockquote style="color: blue; ">Postrenal azotemia: obstruction behind kidneys; initially ratio > 15; ≤15 if obstruction persists</blockquote></li><ul> <li>Disproportionate increase in urea increases ratio to >15.</li> </ul> </ul><li>(4) Persistent obstruction damages tubular epithelium causing renal azotemia (ratio ≤ 15).</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC019016"></a> <br><a name="PB019002"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Elderly patients</b> normally have a decrease in CCr. Therefore, it is important to calculate the dose and dose interval for drugs that are nephrotoxic (e.g., aminoglycosides) in order to avoid precipitating acute renal failure due to nephrotoxic acute tubular necrosis.
<blockquote style="color: blue; ">Nephrotoxic drugs in elderly: most adjust dose and interval for normal ↓ in CCr</blockquote></div><a name="P019013"></a><div class="PA" style="color: black; "><ol type="1"> <li>Correlates with GFR</li><ol type="a"> <li>Annual decrease in CCr of 1 mL/minute after age 50 years
<blockquote style="color: blue; ">CCr: normally decreases with age</blockquote></li><li>Useful in detecting renal dysfunction</li> </ol><li>Creatinine clearance (CCr) formula</li><ol type="a"> <li>Measured CCr = UCr (mg/dL) × V (mL/min) ÷ PCr (mg/dL)</li><ul> <li>(1) V = volume of a 24-hour urine collection in mL/minute, and UCr and PCr are the creatinine concentration of urine and plasma, respectively.</li><li>(2) CCr results are dependent on a correct 24-hour urine collection.</li> </ul><li>Normal adult CCr is 97 to 137 mL/minute.
<blockquote style="color: blue; ">Increased CCr: normal pregnancy, early diabetic glomerulopathy</blockquote></li><ul> <li>(1) In general, CCr < 100 mL/minute is abnormal.</li><li>(2) CCr < 10 mL/minute indicates renal failure.</li> </ul> </ol><li>Causes of increased and decreased CCr (<span>[[Table 19-3|Table 19-3. CAUSES OF INCREASED AND DECREASED CREATININE CLEARANCE (CCr)]]</span>)</li> </ol>
</div></html>
<html><a name="HC019017"></a><span>[[Fig. 19-2|Figure 19-2]]</span> <br><span>[[Table 19-4|Table 19-4. URINALYSIS]]</span> <br> <br><a name="P019014"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Urinalysis: gold standard test to evaluate renal disease</blockquote>
<ul> <li>Gold standard test in the initial workup of renal disease</li> </ul>
</div></html>
![[19.III.A.Serum blood urea nitrogen (BUN)]]
<<tiddler [[19.III.A.Serum blood urea nitrogen (BUN)]]>>
![[19.III.B.Serum creatinine]]
<<tiddler [[19.III.B.Serum creatinine]]>>
![[19.III.C.Serum BUN:creatinine (Cr) ratio]]
<<tiddler [[19.III.C.Serum BUN:creatinine (Cr) ratio]]>>
![[19.III.D.Creatinine clearance (CCr)]]
<<tiddler [[19.III.D.Creatinine clearance (CCr)]]>>
![[19.III.E.Urinalysis (Table 19-4 and Fig. 19-2)]]
<<tiddler [[19.III.E.Urinalysis (Table 19-4 and Fig. 19-2)]]>>
<html><a name="HC019019"></a> <br><a name="PB019003"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Nonsteroidal anti-inflammatory drugs</b> inhibit production of PGE<sub>2</sub>; therefore, intrarenal blood flow is controlled by the efferent arterioles, whose blood flow is maintained by ATII, a vasoconstrictor. This increases the risk of ischemic damage to the medulla.</div><a name="P019016"></a><div class="PA" style="color: black; "><ol type="1"> <li>Renal cortex receives ∼90% of the blood supply.</li><li>Renal medulla is relatively ischemic due to reduced blood supply.
<blockquote style="color: blue; ">Renal medulla: relatively ischemic</blockquote></li><li>Renal vessels are end-arteries.</li><ol type="a"> <li><i>No</i> collateral circulation</li><li>Occlusion of any branch of a renal artery produces infarction.</li> </ol><li>Afferent arterioles</li><ol type="a"> <li>Contain the juxtaglomerular apparatus</li><ul> <li>Produces the enzyme renin
<blockquote style="color: blue; ">Renal PGE<sub>2</sub>: vasodilation afferent arteriole</blockquote></li> </ul><li>Blood flow is controlled by renal-derived PGE<sub>2</sub> (vasodilator).</li><li>Direct blood into the glomerular capillaries</li> </ol><li>Efferent arterioles</li><ol type="a"> <li>Drain the glomerular capillaries</li><li>Blood flow controlled by ATII (vasoconstrictor).
<blockquote style="color: blue; ">ATII: vasoconstrictor of efferent arterioles</blockquote></li><li>Eventually become the peritubular capillaries</li> </ol> </ol>
</div></html>
<html><a name="HC019020"></a><span>[[Fig. 19-3|Figure 19-3]]</span> <br> <br><a name="P019017"></a><div class="PA" style="color: black; "><ol type="1"> <li>Glomerular capillaries contain fenestrated epithelium.</li><ul> <li>Holes in the endothelial surface are important in the filtration process.</li> </ul><li>Glomerular basement membrane (GBM)
<blockquote style="color: blue; ">GBM: size and charge determine protein filtration</blockquote></li><ol type="a"> <li>Composed of type IV collagen</li><li>Size and charge are the primary determinants of protein filtration.</li><ul> <li>(1) Heparan sulfate produces the negative charge of the GBM.</li><li>(2) Cationic proteins of low molecular weight (LMW) are permeable.</li><li>(3) Albumin has a strong negative charge and is <i>not</i> permeable.
<blockquote style="color: blue; ">Albumin: negative charge; repelled by negatively charged GBM</blockquote></li><ul> <li>(a) Loss of the negative charge causes loss of albumin in the urine.</li><li>(b) Called selective proteinuria (e.g., minimal change disease)</li> </ul><li>(4) GBM is permeable to water and LMW (<70,000 daltons) proteins (e.g., amino acids).</li> </ul><li>Causes of GBM thickening</li><ul> <li>(1) Deposition of immunocomplexes</li><ul> <li>Example-membranous glomerulopathy</li> </ul><li>(2) Increased synthesis of type IV collagen</li><ul> <li>Example-diabetes mellitus</li> </ul> </ul> </ol><li>Visceral epithelial cells (VEC)</li><ol type="a"> <li>Primarily responsible for production of the GBM</li><li>Contain podocytes (foot-like processes) and slit pores between the podocytes
<blockquote style="color: blue; ">Fusion of the podocytes: sign of nephrotic syndrome</blockquote></li><ul> <li>Serve as a distal barrier for preventing protein loss in the urine</li> </ul><li>Fusion of the podocytes is present in any cause of the nephrotic syndrome.</li> </ol><li>Mesangial cells</li><ol type="a"> <li>Support the glomerular capillaries</li><li>Can release inflammatory mediators and proliferate</li><ul> <li>Example-IgA glomerulopathy has mesangial immunocomplex deposits.</li> </ul> </ol><li>Parietal epithelial cells</li><ol type="a"> <li>Lining cells of Bowman's capsule
<blockquote style="color: blue; ">Crescents: proliferation of parietal epithelial cells</blockquote></li><li>Proliferation causes "crescents" that encroach upon and destroy the glomerulus.</li> </ol> </ol>
</div></html>
![[19.IV.A.Blood supply of the kidney]]
<<tiddler [[19.IV.A.Blood supply of the kidney]]>>
![[19.IV.B.Structure of the glomerulus (Fig. 19-3)]]
<<tiddler [[19.IV.B.Structure of the glomerulus (Fig. 19-3)]]>>
<html><a name="HC019047"></a> <br><a name="P019049"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common renal disease in essential hypertension</li><li>Pathogenesis</li><ol type="a"> <li>Hyaline arteriolosclerosis of arterioles in the renal cortex.
<blockquote style="color: blue; ">BNS: kidney of essential hypertension; due to hyaline arteriolosclerosis</blockquote></li><li>Causes tubular atrophy, interstitial fibrosis, glomerular sclerosis</li> </ol><li>Small kidneys with a finely granular cortical surface (<span>[[Fig. 19-12|Figure 19-12]]</span>)</li><li>Laboratory findings</li><ol type="a"> <li>Mild proteinuria</li><li>Hematuria (no RBC casts)</li><li>Renal azotemia</li> </ol> </ol>
</div></html>
<html><a name="HC019048"></a> <br><a name="P019050"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Sudden onset of accelerated hypertension</li><ul> <li>(1) May occur in normotensive individuals</li><li>(2) May occur in those with BNS (most common)</li><li>(3) May occur as a complication of various disorders</li> </ul><li>Risk factors</li><ul> <li>(1) Pre-existing BNS (most common)
<blockquote style="color: blue; ">Malignant hypertension: pre-existing BNS most common cause</blockquote></li><li>(2) Hemolytic-uremic syndrome</li><li>(3) Thrombotic thrombocytopenic purpura</li><li>(4) Systemic sclerosis</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Vascular damage to arterioles and small arteries</li><li>Gross and microscopic changes</li><ul> <li>(1) Fibrinoid necrosis and necrotizing arteriolitis and glomerulitis</li><ul> <li>Pinpoint hemorrhages on the cortical surface ("flea-bitten" kidneys)</li> </ul><li>(2) Hyperplastic arteriolosclerosis ("onion skin" lesion; refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>) (<span>[[Fig. 19-13|Figure 19-13]]</span>)</li><ul> <li>Smooth muscle hyperplasia and reduplication of basement membrane</li> </ul> </ul> </ol><li>Clinical findings
<blockquote style="color: blue; ">Malignant hypertension: ≥ 210/120 mm Hg, encephalopathy, renal failure</blockquote></li><ol type="a"> <li>Rapid increase in blood pressure to ≥210/120 mm Hg</li><li>Hypertensive encephalopathy</li><ul> <li>(1) Cerebral edema</li><li>(2) Papilledema</li><ul> <li>Loss of the normal optic nerve disk margin</li> </ul><li>(3) Retinopathy</li><ul> <li>Flame hemorrhages, exudates</li> </ul><li>(4) Potential for an intracerebral bleed</li> </ul><li>Oliguric acute renal failure</li> </ol><li>Laboratory findings</li><ol type="a"> <li>Azotemia with BUN:Cr ratios ≤15</li><li>Hematuria with RBC casts</li><li>Proteinuria
<blockquote style="color: blue; ">Malignant hypertension: IV nitroprusside</blockquote></li> </ol><li>Initial treatment is intravenous sodium nitroprusside.</li> </ol>
</div></html>
<html><a name="HC019049"></a> <br><a name="P019051"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes
<blockquote style="color: blue; ">Renal infarction: embolization most common</blockquote></li><ol type="a"> <li>Embolization from thrombi in the left side of the heart (most common)</li><li>Atheroembolic renal disease</li><li>Vasculitis, particularly polyarteritis nodosa</li> </ol><li>Gross and microscopic appearance</li><ol type="a"> <li>Irregular, wedge-shaped pale infarctions in the cortex</li><li>Old infarcts have a V-shaped appearance due to scar tissue.
<blockquote style="color: blue; ">Renal infarction: hematuria and flank pain</blockquote></li> </ol><li>Sudden onset of flank pain and hematuria</li> </ol>
</div></html>
<html><a name="HC019050"></a> <br><a name="P019052"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Sickle cell trait/disease: hematuria; loss concentration; renal papillary necrosis, APN</blockquote>
<ol type="1"> <li>Occurs with sickle cell trait or disease</li><li>Clinical presentations</li><ol type="a"> <li>Asymptomatic hematuria (most common) (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li><ul> <li>Due to infarctions in the medulla</li> </ul><li>Loss of concentrating ability</li><li>Renal papillary necrosis</li><li>Pyelonephritis</li> </ol> </ol>
</div></html>
<html><a name="HC019051"></a> <br><a name="P019053"></a><div class="PA" style="color: black; "><ol type="1"> <li>Complication of an obstetric emergency</li><ul> <li>Examples-preeclampsia, abruptio placentae</li> </ul><li>Due to DIC limited to the renal cortex</li><ol type="a"> <li>Fibrin clots in arterioles and glomerular capillaries</li><li>Bilateral, diffuse, pale infarct of the renal cortex
<blockquote style="color: blue; ">Diffuse cortical necrosis: anuria followed by ARF in pregnant woman</blockquote></li> </ol><li>Anuria (no urine) in a pregnant woman followed by ARF</li> </ol>
</div></html>
![[19.IX.A.Benign nephrosclerosis (BNS)]]
<<tiddler [[19.IX.A.Benign nephrosclerosis (BNS)]]>>
![[19.IX.B.Malignant hypertension]]
<<tiddler [[19.IX.B.Malignant hypertension]]>>
![[19.IX.C.Renal infarction]]
<<tiddler [[19.IX.C.Renal infarction]]>>
![[19.IX.D.Sickle cell nephropathy]]
<<tiddler [[19.IX.D.Sickle cell nephropathy]]>>
![[19.IX.E.Diffuse cortical necrosis]]
<<tiddler [[19.IX.E.Diffuse cortical necrosis]]>>
<html><a name="HC019022"></a> <br><a name="P019020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common congenital kidney disorder</li><li>Majority (90% of cases) are fused at the lower pole (<span>[[Fig. 19-4|Figure 19-4]]</span>).
<blockquote style="color: blue; ">Horseshoe kidney: association with Turner's syndrome</blockquote></li><ul> <li>Kidney is trapped behind the root of the inferior mesenteric artery.</li> </ul><li>Clinical findings</li><ol type="a"> <li>Increased incidence with Turner's syndrome
<blockquote style="color: blue; ">Renal dysplasia: most common cystic disease in children</blockquote></li><li>Danger of infection and stone formation</li> </ol> </ol>
</div></html>
<html><a name="HC019023"></a><span>[[19-6|Figure 19-6]]</span> <br><span>[[Figs. 19-5|Figure 19-5]]</span> <br><span>[[Table 19-5|Table 19-5. CYSTIC DISEASES OF THE KIDNEYS]]</span> <br> <br></html>
![[19.V.A.Horseshoe kidney]]
<<tiddler [[19.V.A.Horseshoe kidney]]>>
![[19.V.B.Cystic diseases of the kidney (Table 19-5 and Figs. 19-5 and 19-6)]]
<<tiddler [[19.V.B.Cystic diseases of the kidney (Table 19-5 and Figs. 19-5 and 19-6)]]>>
<html><a name="HC019025"></a><span>[[Table 19-6|Table 19-6. NOMENCLATURE AND DESCRIPTION OF GLOMERULAR DISORDERS]]</span> <br> <br><a name="P019024"></a><div class="PA" style="color: black; "><ul> <li>Normal glomerulus (<span>[[Fig. 19-7A|Figure 19-7]]</span>)</li> </ul>
</div></html>
<html><a name="HC019026"></a> <br><a name="P019025"></a><div class="PA" style="color: black; "><ol type="1"> <li>H&E (hematoxylin and eosin) and other special stains</li><ul> <li>Used to help classify the type of glomerular disease</li> </ul><li>Immunofluorescence (IF) stain</li><ol type="a"> <li>Identifies patterns and type of protein deposition</li><li>Linear pattern (<span>[[Fig. 19-7B|Figure 19-7]]</span>)
<blockquote style="color: blue; ">Linear IF: anti-GBM disease (e.g., Goodpasture syndrome)</blockquote></li><ul> <li>(1) It is a characteristic finding in anti-GBM disease.</li><ul> <li>Example-Goodpasture syndrome</li> </ul><li>(2) Antibodies line up against evenly distributed antigens in the GBM.</li><ul> <li>Cannot be detected by electron microscopy</li> </ul> </ul><li>Granular ("lumpy-bumpy") pattern (<span>[[Fig. 19-7C|Figure 19-7]]</span>)
<blockquote style="color: blue; ">Granular pattern: immunocomplex type of glomerulonephritis</blockquote></li><ul> <li>Usually indicates immunocomplex (IC) deposition in the glomerulus</li> </ul> </ol><li>Electron microscopy (EM)</li><ol type="a"> <li>Detects submicroscopic defects in the glomerulus; examples:</li><ul> <li>(1) Fusion of podocytes in the nephrotic syndrome (<span>[[Fig. 19-7D|Figure 19-7]]</span>)</li><li>(2) Damage to visceral epithelial cells</li> </ul><li>Detects the site(s) of IC deposition</li><ul> <li>(1) Deposits are electron-dense (dark color)
<blockquote style="color: blue; ">EM: immunocomplex deposits are electron-dense</blockquote></li><li>(2) Sites are designated</li><ul> <li>(a) Subendothelial (<span>[[Fig. 19-7E|Figure 19-7]]</span>)</li><ul> <li>Trapped between the endothelial cell and GBM</li> </ul><li>(b) Subepithelial (<span>[[Fig. 19-7F|Figure 19-7]]</span>)</li><ul> <li>Passed through the GBM but caught beneath the podocytes</li> </ul><li>(c) Intramembranous</li><ul> <li>Within the GBM</li> </ul><li>(d) Mesangial</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC019027"></a> <br><a name="P019026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Immunocomplexes (type III hypersensitivity)
<blockquote style="color: blue; ">Immunocomplexes: most common mechanism causing glomerulonephritis</blockquote></li><ol type="a"> <li>Circulate and deposit in glomeruli or they develop in situ</li><ul> <li>Example: DNA-anti-DNA complexes in SLE</li> </ul><li>ICs activate the complement system.</li><ul> <li>(1) C5a is produced, which is chemotactic to neutrophils.
<blockquote style="color: blue; ">Immunocomplexes: activate complement → C5a produced → attracts neutrophils</blockquote></li><li>(2) Neutrophils damage the glomeruli.</li><ul> <li>Damage to the glomeruli by neutrophils, which occurs in nephritic types of glomerulonephritis.</li> </ul> </ul> </ol><li>Antibodies directed against GBM antigens</li><ul> <li>Example-Goodpasture syndrome</li> </ul><li>T-cell production of cytokines</li><ol type="a"> <li>Cytokines cause the GBM to lose its negative charge.</li><li>Cytokines damage podocytes causing them to fuse.</li><li>Example-minimal change disease in the nephrotic syndrome</li> </ol> </ol>
</div></html>
<html><a name="HC019028"></a> <br><a name="P019027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Nephritic syndrome</li><li>Nephrotic syndrome</li><li>Chronic glomerulonephritis</li> </ol>
</div></html>
<html><a name="HC019029"></a> <br><a name="P019028"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Nephritic syndrome: neutrophil-related injury to glomeruli</blockquote>
<ol type="1"> <li>Glomerular injury is primarily due to neutrophils.</li><li>Clinical and laboratory findings</li><ol type="a"> <li>Hypertension</li><ul> <li>Due to salt retention</li> </ul><li>Periorbital puffiness</li><ul> <li>(1) Due to salt retention in the loose skin in that area</li><li>(2) In some cases, edema can be more generalized.
<blockquote style="color: blue; ">Pitting edema: does <i>not</i> distinguish nephritic from nephrotic syndrome</blockquote></li><ul> <li>Sodium retention increases plasma hydrostatic pressure.</li> </ul> </ul><li>Oliguria (∼400 mL urine/day)</li><ul> <li>(1) Due to decreased GFR from inflamed glomeruli</li><li>(2) Tubular function is intact.</li> </ul><li>Hematuria</li><ul> <li>(1) Dysmorphic RBCs with irregular membranes (see <span>[[Fig. 19-2A|Figure 19-2]]</span>)</li><li>(2) Due to inflamed glomeruli from IC deposition</li> </ul><li>Neutrophils in the sediment (see <span>[[Fig. 19-2B|Figure 19-2]]</span>)</li><ul> <li>Particularly in IC types</li> </ul><li>RBC casts are a key finding (see <span>[[Fig. 19-2E|Figure 19-2]]</span>).
<blockquote style="color: blue; ">Nephritic syndrome: moderate proteinuria; dysmorphic RBCs, RBC casts</blockquote></li><ul> <li>Occasionally, WBC casts are also present.</li> </ul><li>Proteinuria > 150 mg/day, but <3.5 g/day</li><li>Azotemia with a BUN:Cr ratio > 15</li><ul> <li>Tubular function is intact in acute glomerulonephritis.</li> </ul> </ol><li>Primarily nephritic types of glomerular disease (<span>[[Table 19-7|Table 19-7. PRIMARILY NEPHRITIC TYPES OF GLOMERULAR DISEASE]]</span>; see also <span>[[Fig. 19-7B to H|Figure 19-7]]</span>)</li> </ol>
</div></html>
<html><a name="HC019030"></a> <br><a name="P019029"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Nephrotic syndrome: cytokine injury to podocytes; loss of negative charge on GBM</blockquote>
<ol type="1"> <li>Glomerular injury is due to cytokines <i>not</i> neutrophils.</li><ol type="a"> <li>Cytokines damage podocytes causing them to fuse together.</li><li>Cytokines destroy the negative charge of the GBM.</li> </ol><li>Clinical and laboratory findings</li><ol type="a"> <li>Key finding is proteinuria > 3.5 g/24 hours.
<blockquote style="color: blue; ">Nephrotic syndrome: proteinuria > 3.5 g/24 hours; fatty casts</blockquote></li><li>Generalized pitting edema and ascites</li><ul> <li>(1) Due to hypoalbuminemia</li><ul> <li>Pitting edema in nephritic syndrome is due to sodium retention.</li> </ul><li>(2) Increased risk for developing spontaneous peritonitis (refer to <span macro="tag [[18 Hepatobiliary and Pancreatic Disorders]] [[Chapter 18]]"></span>)</li><ul> <li>Due to <i>Streptococcus pneumoniae</i></li> </ul> </ul><li>Hypertension in some types</li><ul> <li>Due to sodium retention</li> </ul><li>Hypercoagulable state due to loss of antithrombin III</li><ul> <li>Potential for renal vein thrombosis</li> </ul><li>Hypercholesterolemia</li><ul> <li>Hypoalbuminemia increases synthesis of cholesterol (unknown mechanism).</li> </ul><li>Hypogammaglobulinemia</li><ul> <li>Due to the loss of γ-globulins in the urine</li> </ul><li>Fatty casts with maltese crosses and oval fat bodies (see <span>[[Fig. 19-2C|Figure 19-2]]</span>)
<blockquote style="color: blue; ">Nephrotic syndrome: less glomerular inflammation than nephritic syndrome</blockquote></li><ul> <li>Key finding of the nephrotic syndrome</li> </ul> </ol><li>Primarily nephrotic types of glomerular disease (<span>[[Table 19-8|Table 19-8. PRIMARILY NEPHROTIC TYPES OF GLOMERULAR DISEASE]]</span>; see <span>[[Fig. 19-7D, F, and I|Figure 19-7]]</span>)</li> </ol>
</div></html>
<html><a name="HC019031"></a> <br><a name="PB019004"></a><div class="BB" style="color: rgb(47, 79, 79); ">An <b>angiotensin-converting enzyme (ACE) inhibitor</b> is prescribed when microalbuminuria is first detected. It slows the progression of diabetic glomerulopathy and retinopathy in both types of diabetes mellitus. One possible mechanism is by reducing pressure in the glomerular capillaries by decreasing ATII vasoconstriction of the hyalinized efferent arterioles. Angiotensin receptor blockers are also useful, particularly in type 2 diabetes mellitus. These changes are independent of the blood pressure lowering capabilities of both drugs.
<blockquote style="color: blue; ">ACE inhibitor/receptor blockers: slow progression of nephropathy in type 1/type 2 diabetes</blockquote></div><a name="P019030"></a><div class="PA" style="color: black; "><ol type="1"> <li>Diabetic glomerulopathy</li><ul> <li>Nodular glomerulosclerosis (Kimmelstiel-Wilson disease)</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Glomerulopathy occurs in type 1 and 2 diabetes.</li><ul> <li>Occurs more often in type 1 (35-45%) than type 2 diabetes (20%)</li> </ul><li>(2) Most common cause of chronic renal failure in United States
<blockquote style="color: blue; ">Diabetic glomerulopathy: type 1 > type 2 diabetes</blockquote></li><ul> <li>Type 1 > type 2 diabetes mellitus</li> </ul><li>(3) Risk factors</li><ul> <li>(a) Poor glycemic control
<blockquote style="color: blue; ">Diabetic glomerulopathy: poor glycemic control is the most common cause</blockquote></li><li>(b) Hypertension</li><li>(c) Diabetic retinopathy</li><ul> <li>High correlation with coexisting glomerulopathy</li> </ul> </ul> </ul><li>Pathogenesis</li><ul> <li>(1) Nonenzymatic glycosylation (NEG) of the GBM</li><ul> <li>Also affects tubule basement membranes</li> </ul><ul> <li>(a) Glycosylation refers to glucose attaching to amino acids.
<blockquote style="color: blue; ">NEG: ↑ vessel/tubular permeability to protein</blockquote></li><li>(b) Increases vessel and tubular cell permeability to proteins</li> </ul><li>(2) NEG of the afferent and efferent arterioles</li><ul> <li>(a) Produces hyaline arteriolosclerosis (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)</li><li>(b) Involves efferent arterioles <i>before</i> afferent arterioles</li> </ul><li>(3) Osmotic damage to glomerular capillary endothelial cells
<blockquote style="color: blue; ">Osmotic damage: ↑ sorbitol</blockquote></li><ul> <li>(a) Glucose is converted by aldose reductase into sorbitol.</li><li>(b) Sorbitol is osmotically active.</li><li>(c) Water enters the cells causing damage.</li> </ul><li>(4) Hyperfiltration damage to the mesangium
<blockquote style="color: blue; ">Hyaline arteriolosclerosis of efferent arteriole: ↑ GFR producing hyperfiltration injury</blockquote></li><ul> <li>(a) Selective hyaline arteriolosclerosis of efferent arterioles</li><li>(b) Increases the GFR, which damages mesangial cells</li> </ul><li>(5) Diabetic microangiopathy; increased deposition of type IV collagen</li><ul> <li>GBM, tubular cell basement membranes, mesangium</li> </ul> </ul><li>Nonspecific immunofluorescence</li><li>Electron microscope shows fusion of podocytes (see <span>[[Fig. 19-7D|Figure 19-7]]</span>).</li><li>Microscopic findings (see <span>[[Fig. 19-7J|Figure 19-7]]</span>)</li><ul> <li>(1) Afferent and efferent hyaline arteriolosclerosis</li><ul> <li>When the afferent arteriole becomes hyalinized, the GFR decreases.
<blockquote style="color: blue; ">Microangiopathy: ↑ deposition type IV collagen</blockquote></li> </ul><li>(2) Nodular masses develop in the mesangial matrix.</li><ul> <li>Due to increased type IV collagen synthesis and trapped proteins</li> </ul> </ul><li>Clinical and laboratory findings</li><ul> <li>(1) Microalbuminuria
<blockquote style="color: blue; ">Microalbuminuria: first laboratory sign of diabetic glomerulopathy</blockquote></li><ul> <li>(a) Initial laboratory manifestation of diabetic glomerulopathy</li><ul> <li>Usually begins after ∼10 years of poor glycemic control</li> </ul><li>(b) Microalbuminuria dipsticks detect albumin levels in the range of 1.5 to 8 mg/dL.</li> </ul><li>(2) Other renal diseases associated with diabetes mellitus</li><ul> <li>Renal papillary necrosis, acute and chronic pyelonephritis</li> </ul> </ul> </ol> </ul><li>Renal amyloidosis (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>, see <span>[[Figs. 3-6|Figure 3-6]]</span> and <span>[[3-7|Figure 3-7]]</span>)</li><ul> <li>Associated with primary and secondary amyloidosis</li> </ul> </ol>
</div></html>
![[19.VI.A.Terminology of glomerular disease (Table 19-6)]]
<<tiddler [[19.VI.A.Terminology of glomerular disease (Table 19-6)]]>>
![[19.VI.B.Routine studies on biopsy specimens]]
<<tiddler [[19.VI.B.Routine studies on biopsy specimens]]>>
![[19.VI.C.Mechanisms producing glomerular disease]]
<<tiddler [[19.VI.C.Mechanisms producing glomerular disease]]>>
![[19.VI.D.Clinical manifestations of glomerular diseases]]
<<tiddler [[19.VI.D.Clinical manifestations of glomerular diseases]]>>
![[19.VI.E.Nephritic syndrome]]
<<tiddler [[19.VI.E.Nephritic syndrome]]>>
![[19.VI.F.Nephrotic syndrome]]
<<tiddler [[19.VI.F.Nephrotic syndrome]]>>
![[19.VI.G.Systemic diseases with nephrotic syndrome]]
<<tiddler [[19.VI.G.Systemic diseases with nephrotic syndrome]]>>
![[19.VI.H.Hereditary glomerular diseases]]
<<tiddler [[19.VI.H.Hereditary glomerular diseases]]>>
![[19.VI.I.Chronic glomerulonephritis]]
<<tiddler [[19.VI.I.Chronic glomerulonephritis]]>>
<html><a name="HC019032"></a> <br><a name="P019031"></a><div class="PA" style="color: black; "><ol type="1"> <li>Alport's syndrome</li><ol type="a"> <li>Autosomal dominant disease; perhaps X-linked recessive</li><ul> <li>Autoantibodies to type IV collagen in GBM</li> </ul><li><i>No</i> specific immunofluorescence or electron microscopic findings
<blockquote style="color: blue; ">Alport's syndrome: hereditary nephritis, sensorineural hearing loss, ocular defects</blockquote></li><li>Microscopic findings</li><ul> <li>Lipid accumulation in VECs producing foam cells</li> </ul><li>Sensorineural hearing loss and ocular abnormalities</li> </ol><li>Thin basement membrane disease</li><ul> <li>"Benign familial hematuria"</li><ol type="a"> <li>Autosomal dominant disorder</li><li>Extremely thin GBMs
<blockquote style="color: blue; ">Thin basement membrane disease: persistent hematuria</blockquote></li><ul> <li>Normal renal function</li> </ul><li>Mild proteinuria, persistent microscopic hematuria</li> </ol> </ul> </ol>
</div></html>
<html><a name="HC019033"></a> <br><a name="P019032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes in descending order of incidence:</li><ol type="a"> <li>Rapidly progressive glomerulonephritis (RPGN; 90%)
<blockquote style="color: blue; ">RPGN: most common cause of chronic glomerulonephritis</blockquote></li><li>Focal segmental glomerulosclerosis (80%)</li><li>Type I membranoproliferative glomerulonephritis (40%)</li><li>Membranous glomerulopathy (20-30%)</li><li>Type IV diffuse proliferative glomerulonephritis in SLE (20%)</li><li>IgA glomerulopathy (10%)</li> </ol><li>Gross and microscopic findings</li><ol type="a"> <li>Shrunken kidneys</li><li>Glomerular sclerosis and tubular atrophy</li> </ol> </ol>
</div></html>
<html><a name="HC019035"></a> <br><a name="P019034"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Greater than 10% of intensive care unit patients develop acute renal failure (ARF).</li><li>Greater than 40% of hospital ARF is iatrogenic (doctor-induced).</li><li>ARF occurs in 20% of patients with sepsis.</li><li>ARF develops in >50% of patients with septic shock.</li><li>Acute renal failure (ARF)</li><ul> <li>(1) Acute suppression of renal function developing in 24 hours</li><li>(2) Accompanied by anuria or oliguria (∼400 mL/24 hours)
<blockquote style="color: blue; ">ATN: most common cause of ARF</blockquote></li><li>(3) ATN is the most common cause of ARF.</li><ul> <li>Subdivided into ischemic and nephrotoxic types
<blockquote style="color: blue; ">Ischemic ATN: most common type of ATN</blockquote></li> </ul> </ul><li>Other causes of ARF</li><ul> <li>(1) Postrenal obstruction</li><ul> <li>Examples-prostate hyperplasia; invasive cervical cancer</li> </ul><li>(2) Vascular disease</li><ul> <li>Example-malignant hypertension</li> </ul><li>(3) RPGN, drugs, disseminated intravascular coagulation (DIC), urate nephropathy</li> </ul> </ol><li>Ischemic ATN</li><ol type="a"> <li>Most often caused by prerenal azotemia due to hypovolemia
<blockquote style="color: blue; ">Prerenal azotemia: most common cause of ischemic ATN</blockquote></li><li>Ischemia damages endothelial cells.</li><ul> <li>(1) Causes decrease in vasodilators</li><ul> <li>Examples-nitric oxide, PGI<sub>2</sub></li> </ul><li>(2) Increase in vasoconstrictors</li><ul> <li>Example-endothelin</li> </ul><li>(3) Net effect is vasoconstriction of afferent arterioles, which decreases GFR.</li> </ul><li>Ischemia damages tubule cells</li><ul> <li>(1) Causes detachment of tubular cells into the lumen causing obstruction (<span>[[Fig. 19-8|Figure 19-8]]</span>)</li><ul> <li>Produces pigmented renal tubular cell casts (see <span>[[Fig. 19-2G|Figure 19-2]]</span>)
<blockquote style="color: blue; ">Renal tubular cell cast: key cast of ATN</blockquote></li> </ul><li>(2) Casts obstruct the lumen causing an increase in intratubular pressure.</li><ul> <li>(a) Decreases GFR</li><li>(b) Pushes fluid into the interstitium</li><li>(c) Net effect is oliguria.</li> </ul> </ul><li>Sites of tubular damage</li><ul> <li>(1) Straight segment of proximal tubule</li><ul> <li>Part of the nephron most susceptible to hypoxia</li> </ul><li>(2) Medullary segment of the thick ascending limb (TAL)</li><ul> <li>Location of the Na<sup>+</sup>-K<sup>+</sup>-2 Cl<sup>-</sup> cotransporter</li> </ul><li>(3) Tubular basement membranes are disrupted at these sites.</li><ul> <li>Interferes with renal tubular cell regeneration</li> </ul> </ul> </ol><li>Nephrotoxic type</li><ol type="a"> <li>Causes</li><ul> <li>(1) Aminoglycosides most common cause (e.g., gentamicin)
<blockquote style="color: blue; ">Aminoglycosides: most common cause of nephrotoxic ATN</blockquote></li><li>(2) Radiocontrast agents</li><li>(3) Heavy metals (e.g., lead and mercury)</li> </ul><li>Microscopic findings</li><ul> <li>(1) Primarily damages the proximal tubule cells</li><li>(2) Tubular basement membrane is intact.</li> </ul> </ol><li>Clinical and laboratory findings in ATN</li><ol type="a"> <li>Oliguria, in most cases</li><ul> <li>Some cases have polyuria (∼800 mL/24 hours).
<blockquote style="color: blue; ">ATN: renal tubular cell casts</blockquote></li> </ul><li>Pigmented renal tubular cell casts (see <span>[[Fig. 19-2G|Figure 19-2]]</span>)</li><li>Hyperkalemia, increased anion gap metabolic acidosis (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li><li>Increased serum BUN and creatinine (ratio ≤ 15)
<blockquote style="color: blue; ">BUN: creatinine ratio ≤15; hyperkalemia, metabolic acidosis</blockquote></li><li>Hypokalemia (diuresis phase) and infection are common problems</li> </ol><li>Treatment</li><ol type="a"> <li>Treat prerenal azotemia</li><ul> <li>Volume expansion if hypovolemic; increase renal blood flow</li> </ul><li>Low dose dopamine</li><li>Fenoldopam (dopamine α-1-receptor agonist)</li><li>Dialysis</li> </ol><li>Differential diagnosis of oliguria (<span>[[Box 19-1|BOX 19-1 DIFFERENTIAL DIAGNOSIS OF OLIGURIA]]</span>)</li> </ol>
</div></html>
<html><a name="HC019036"></a> <br><a name="PB019005"></a><div class="BB" style="color: rgb(47, 79, 79); ">Patients with disseminated cancers should receive allopurinol, an xanthine oxidase inhibitor, <i>before</i> being treated with chemotherapy. This prevents urate nephropathy (tumor lysis syndrome) and acute renal failure.
<blockquote style="color: blue; ">Prevention of urate nephropathy: allopurinol <i>before</i> aggressive cancer therapy</blockquote></div><a name="P019035"></a><div class="PA" style="color: black; "><ol type="1"> <li>Overview</li><ul> <li>Acute or chronic inflammation of tubules and interstitium</li><ol type="a"> <li>Causes of TIN</li><ul> <li>Acute pyelonephritis (APN; most common)
<blockquote style="color: blue; ">APN: most common cause of TIN</blockquote></li> </ul><li>Drugs</li><li>Infections</li><ul> <li>Examples-legionnaires' disease, leptospirosis</li> </ul><li>SLE, lead poisoning</li><li>Urate nephropathy, multiple myeloma</li> </ol> </ul><li>Acute pyelonephritis</li><ol type="a"> <li>Epidemiology
<blockquote style="color: blue; ">APN: most common cause of TIN</blockquote></li><ul> <li>(1) More common in women than men</li><ul> <li>Women have a short urethra.
<blockquote style="color: blue; ">APN: women > men</blockquote></li> </ul><li>(2) <i>Escherichia coli</i> most common cause</li><ul> <li><i>Enterococcus</i> second in frequency
<blockquote style="color: blue; ">APN: <i>E. coli</i> most common cause</blockquote></li> </ul><li>(3) Risk factors</li><ul> <li>(a) Indwelling urinary catheter</li><li>(b) Urinary tract obstruction</li><li>(c) Medullary sponge kidney</li><li>(d) Diabetes mellitus, pregnancy</li><li>(e) Sickle cell trait/disease</li> </ul> </ul><li>Pathogenesis</li><ul> <li>(1) Vesicoureteral reflux (VUR) with ascending infection (most common)</li><ul> <li>(a) Intravesical portion of the ureter is normally compressed with micturition.</li><ul> <li>Prevents reflux of urine into the ureter(s)</li> </ul><li>(b) In VUR, the intravesical portion of the ureter is <i>not</i> compressed during micturition.
<blockquote style="color: blue; ">VUR: urine refluxes into the ureters during micturition</blockquote></li><ul> <li>Urine refluxes into the ureter(s).</li> </ul><li>(c) Should be corrected by reimplantation of the ureters/stents</li> </ul><li>(2) Ascending infection</li><ul> <li>(a) Most common mechanism for lower and upper UTIs in females
<blockquote style="color: blue; ">Ascending infection: most common mechanism for upper/lower UTIs in females</blockquote></li><li>(b) Distal urethra and vaginal introitus are normally colonized by <i>Escherichia coli.</i></li><li>(c) Organisms ascend into the urethra and bladder.</li><ul> <li>Causes urethritis and cystitis</li> </ul><li>(d) If VUR is present, infected urine ascends to the renal pelvis and renal parenchyma.</li><ul> <li>Causes APN</li> </ul> </ul><li>(3) Hematogenous spread to kidneys</li><ul> <li>(a) Uncommon cause of APN</li><li>(b) Suspect if <i>Staphylococcus aureus</i> is cultured in urine</li> </ul> </ul><li>Gross and microscopic findings</li><ul> <li>(1) Grayish white areas of abscess formation are in the cortex and medulla.</li><li>(2) Microabscess formation occurs in the tubular lumens and interstitium (<span>[[Fig. 19-9|Figure 19-9]]</span>).</li> </ul><li>Clinical findings
<blockquote style="color: blue; ">Findings in APN and <i>not</i> lower UTIs: fever, flank pain, WBC casts in urine</blockquote></li><ul> <li>(1) Spiking fever, flank pain</li><li>(2) Increased frequency of urination</li><li>(3) Painful urination (dysuria)</li> </ul><li>Laboratory findings</li><ul> <li>(1) WBC casts (key finding; see <span>[[Fig. 19-2F|Figure 19-2]]</span>)</li><li>(2) Pyuria, bacteriuria (usually <i>E. coli</i>)</li><li>(3) Hematuria</li> </ul><li>Complications</li><ul> <li>(1) Chronic pyelonephritis</li><li>(2) Perinephric abscess</li><li>(3) Renal papillary necrosis</li><li>(4) Septicemia with endotoxic shock</li> </ul><li>Treatment</li><ul> <li>(1) Ciprofloxacin given orally if uncomplicated</li><li>(2) Ciprofloxacin IV if hospitalized</li><li>(3) Repair VUR</li> </ul> </ol><li>Chronic pyelonephritis (CPN)</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) VUR starting in young girls
<blockquote style="color: blue; ">Causes of CPN: VUR in young girls, chronic hydronephrosis</blockquote></li><li>(2) Lower urinary tract obstruction</li><ul> <li>(a) Produces hydronephrosis</li><li>(b) Examples-prostate hyperplasia, renal stones</li> </ul> </ul><li>Gross and microscopic findings</li><ul> <li>(1) Reflux type of CPN</li><ul> <li>(a) U-shaped cortical scars (<span>[[Fig. 19-10|Figure 19-10]]</span>) overlying a blunt calyx
<blockquote style="color: blue; ">CPN: cortical scars overlie blunt calyces; visible with IVP</blockquote></li><li>(b) Visible with an intravenous pyelogram (IVP)</li> </ul><li>(2) Obstructive type CPN</li><ul> <li>(a) Uniform dilation of the calyces</li><li>(b) Diffuse thinning of cortical tissue</li> </ul><li>(3) Microscopic findings</li><ul> <li>(a) Chronic inflammation
<blockquote style="color: blue; ">CPN: glomerular scarring; tubular atrophy ("thyroidization")</blockquote></li><ul> <li>Secondary scarring of the glomeruli</li> </ul><li>(b) Tubular atrophy</li><ul> <li>Tubules contain eosinophilic material resembling thyroid tissue ("thyroidization").</li> </ul> </ul> </ul><li>Clinical and laboratory findings</li><ul> <li>(1) Usually a history of recurrent APN</li><li>(2) May cause hypertension</li><ul> <li>Reflux nephropathy is a cause of hypertension in children.
<blockquote style="color: blue; ">Reflux nephropathy: hypertension in children</blockquote></li> </ul><li>(3) May cause chronic renal failure (CRF)</li> </ul> </ol><li>Acute drug-induced TIN</li><ol type="a"> <li>Common drug associations
<blockquote style="color: blue; ">Drugs: methicillin, NSAIDs, rifampin, sulfonamides</blockquote></li><ul> <li>(1) Penicillin, particularly methicillin</li><li>(2) Rifampin, sulfonamides</li><li>(3) NSAIDs, diuretics</li> </ul><li>Pathogenesis</li><ul> <li>(1) Combination of type I and type IV hypersensitivity</li><li>(2) Occurs ∼2 weeks after beginning a drug</li> </ul><li>Clinical and laboratory findings
<blockquote style="color: blue; ">Acute drug-induced TIN: abrupt onset fever, oliguria, rash</blockquote></li><ul> <li>(1) Abrupt onset of fever, oliguria, and rash</li><ul> <li>Withdrawal of the drug causes reversal of the disease.</li> </ul><li>(2) Laboratory findings</li><ul> <li>(a) BUN:Cr ratio ≤15</li><li>(b) Eosinophilia and eosinophiluria (highly predictive)</li> </ul> </ul><li>Treatment is to withdraw the drug.</li> </ol><li>Analgesic nephropathy</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Common cause of chronic drug-induced TIN</li><li>(2) More common in women than men</li><li>(3) Usually occurs in patients with chronic pain</li> </ul><li>Pathogenesis</li><ul> <li>(1) Chronic use of acetaminophen plus aspirin for 3 or more years
<blockquote style="color: blue; ">Analgesic nephropathy: acetaminophen + aspirin; renal papillary necrosis</blockquote></li><li>(2) Acetaminophen free radicals damage renal tubules in medulla (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>).</li><li>(3) Aspirin inhibits renal synthesis of PGE<sub>2</sub> leaving ATII unopposed.</li><ul> <li>Decreased blood flow to the renal medulla</li> </ul> </ul><li>Complications</li><ul> <li>(1) Renal papillary necrosis (<span>[[Fig. 19-11|Figure 19-11]]</span>)</li><ul> <li>(a) Sloughing of renal papillae</li><ul> <li>Produces gross hematuria, proteinuria, and colicky flank pain
<blockquote style="color: blue; ">Renal papillary necrosis: "ring defect" on IVP from sloughing of papilla</blockquote></li> </ul><li>(b) An IVP shows a "ring defect" where one or more papillae used to reside.</li><li>(c) Other causes of renal papillary necrosis</li><ul> <li>Diabetes, sickle cell trait/disease, APN</li> </ul> </ul><li>(2) Hypertension, CRF</li><li>(3) Renal pelvic and bladder transitional cell carcinomas</li> </ul> </ol><li>Urate nephropathy</li><ol type="a"> <li>Deposition of urate crystals in the tubules and interstitium</li><li>Causes</li><ul> <li>(1) Massive release of purines (precursor of uric acid)</li><ul> <li>Usually following aggressive treatment of disseminated cancer (e.g., leukemia)</li> </ul><li>(2) Lead poisoning, gout</li> </ul><li>May produce ARF</li> </ol><li>Chronic lead poisoning
<blockquote style="color: blue; ">Chronic Pb poisoning: proximal tubules with nuclear acid-fast inclusions</blockquote></li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Decreases excretion of uric acid (urate nephropathy)</li><ul> <li>Can also decrease uric acid secretion producing gout</li> </ul><li>(2) Direct toxic effect produces TIN</li> </ul><li>Proximal tubule cells contain characteristic nuclear acid-fast inclusions.</li> </ol><li>Multiple myeloma: mechanisms for renal disease</li><ol type="a"> <li>Bence Jones (BJ) proteinuria (refer to <span macro="tag [[13 Lymphoid Tissue Disorders]] [[Chapter 13]]"></span>)</li><ul> <li>(1) BJ protein produces tubular casts.
<blockquote style="color: blue; ">BJ proteinuria: casts with foreign body giant cell reaction</blockquote></li><ul> <li>Light chains are toxic to renal tubular epithelium.</li> </ul><li>(2) Casts obstruct the lumen and incite a foreign body giant cell reaction.</li><ul> <li>Reaction involves tubules and interstitium leading to renal failure.</li> </ul> </ul><li>Nephrocalcinosis (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li><ul> <li>(1) Due to hypercalcemia</li><ul> <li>Metastatic calcification of the basement membrane of collecting tubules</li> </ul><li>(2) Causes polyuria and renal failure</li> </ul><li>Primary amyloidosis producing nephrotic syndrome (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>)</li><ul> <li>Light chains are converted to amyloid (see <span>[[Figs. 3-6|Figure 3-6]]</span> and <span>[[3-7|Figure 3-7]]</span>).</li> </ul> </ol> </ol>
</div><a name="B019001"></a><div class="BT">BOX 19-1 DIFFERENTIAL DIAGNOSIS OF OLIGURIA</div><a name="PB019006"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Oliguria</b> is defined as a urine output < 400 mL/day or <20 mL/hour. The major causes of oliguria include prerenal azotemia (most common cause), acute glomerulonephritis (nephritic type), acute tubular necrosis (renal azotemia), and postrenal azotemia. Laboratory tests that are commonly used in differentiating the types of oliguria include urine osmolality (UOsm), fractional excretion of sodium (FENa<sup>+</sup>), random urine sodium (UNa<sup>+</sup>), and the serum BUN:Cr (blood urea nitrogen/creatinine) ratio (see section III). These tests evaluate tubular function. A UOsm > 500 mOsm/kg indicates good concentrating ability and intact tubular function, but a UOsm < 350 mOsm/kg indicates poor concentrating ability and tubular dysfunction. The FENa<sup>+</sup> represents the amount of sodium excreted in the urine divided by the amount of sodium that is filtered by the kidneys. The calculation is as follows:
where UNa<sup>+</sup> is a random urine sodium, PNa<sup>+</sup> is serum sodium, UCr is random urine creatinine, and PCr is plasma creatinine. Creatinine is used in the formula, because the amount of sodium filtered is dependent on the glomerular filtration rate (GFR), which closely approximates the creatinine clearance (CCr). An FENa<sup>+</sup> < 1% indicates good tubular function and <i>excludes</i> acute tubular necrosis (ATN) as a cause of oliguria. An FENa<sup>+</sup> > 2% indicates tubular dysfunction and is highly predictive of ATN as the cause of oliguria. A random UNa<sup>+</sup> < 20 mEq/L indicates intact tubular function, while a random UNa<sup>+</sup> > 40 mEq/L indicates tubular dysfunction. A serum BUN:Cr ratio > 15 indicates intact tubular function, but a serum BUN:Cr ratio ≤ 15 indicates tubular dysfunction. In prerenal azotemia and acute glomerulonephritis (nephritic type) tubular function is preserved. In order to distinguish the two, the urine sediment examination is most useful. In prerenal azotemia, the urine sediment has <i>no</i> abnormal findings or may have a few hyaline casts. The sediment in acute glomerulonephritis (nephritic type) has hematuria and RBC casts. ATN and postrenal azotemia (long-standing obstruction) both have tubular dysfunction. Postrenal azotemia of short duration has normal tubular function and has laboratory findings similar to prerenal azotemia. In order to distinguish ATN from postrenal azotemia as a cause of tubular dysfunction and oliguria, the urine sediment is most useful. In ATN, the sediment has pigmented renal tubular cell casts, but in postrenal azotemia, the sediment is usually normal. In addition, the patient will likely have a history of a renal stone, benign prostatic hyperplasia, or cervical cancer, which commonly obstructs the ureters where they enter the urinary bladder.</div></html>
![[19.VII.A.Acute tubular necrosis (ATN)]]
<<tiddler [[19.VII.A.Acute tubular necrosis (ATN)]]>>
![[19.VII.B.Tubulointerstitial nephritis (TIN)]]
<<tiddler [[19.VII.B.Tubulointerstitial nephritis (TIN)]]>>
<html><a name="HC019038"></a> <br><a name="P019041"></a><div class="PA" style="color: black; "><ol type="1"> <li>Progressive irreversible azotemia that develops over months to years</li><li>Culminates in end-stage renal disease</li><ol type="a"> <li>Kidneys no longer function well enough to sustain life.</li><li>GFR < 10 mL/minute.</li> </ol><li>Primary causes, in descending order</li><ol type="a"> <li>Diabetic mellitus (37%)</li><li>Hypertension (30%)</li><li>Chronic glomerulonephritis (12%)</li><ul> <li>Particularly due to RPGN and focal segmental glomerulosclerosis</li> </ul><li>Cystic renal disease</li><ul> <li>Renal dysplasia in children, adult polycystic kidney disease</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC019039"></a> <br><a name="P019042"></a><div class="PA" style="color: black; "><ul> <li>Bilateral, small shrunken kidneys</li> </ul>
</div></html>
<html><a name="HC019040"></a> <br><a name="P019043"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">CRF: normocytic anemia; qualitative platelet defect</blockquote>
<ol type="1"> <li>Normocytic anemia with corrected reticulocyte count < 3% (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li><ul> <li>Primarily due to decreased erythropoietin</li> </ul><li>Qualitative platelet defects (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>)</li> </ol>
</div></html>
![[19.VIII.A.Epidemiology and pathogenesis]]
<<tiddler [[19.VIII.A.Epidemiology and pathogenesis]]>>
![[19.VIII.B.Gross appearance]]
<<tiddler [[19.VIII.B.Gross appearance]]>>
![[19.VIII.C.Hematologic findings]]
<<tiddler [[19.VIII.C.Hematologic findings]]>>
![[19.VIII.D.Renal osteodystrophy]]
<<tiddler [[19.VIII.D.Renal osteodystrophy]]>>
![[19.VIII.E.Cardiovascular findings]]
<<tiddler [[19.VIII.E.Cardiovascular findings]]>>
![[19.VIII.F.Miscellaneous findings]]
<<tiddler [[19.VIII.F.Miscellaneous findings]]>>
![[19.VIII.G.Laboratory findings]]
<<tiddler [[19.VIII.G.Laboratory findings]]>>
![[19.VIII.H.Treatment]]
<<tiddler [[19.VIII.H.Treatment]]>>
<html><a name="HC019041"></a> <br><a name="P019044"></a><div class="PA" style="color: black; "><ol type="1"> <li>Osteitis fibrosa cystica</li><ol type="a"> <li>Due to hypovitaminosis D (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>)</li><ul> <li>(1) Causes hypocalcemia, which stimulates production of parathyroid hormone (PTH)</li><li>(2) Called secondary hyperparathyroidism (HPTH) (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li> </ul><li>Secondary HPTH increases bone resorption.
<blockquote style="color: blue; ">Renal osteodystrophy: due to secondary HPTH, osteomalacia, osteoporosis</blockquote></li><ul> <li>(1) Causes cystic lesions in bone (e.g., jaw)</li><li>(2) Hemorrhage into cysts causes a brown discoloration.</li> </ul> </ol><li>Osteomalacia</li><ol type="a"> <li>Decreased mineralization of the organic bone matrix (osteoid)</li><li>In CRF, it is due to hypovitaminosis D.</li><ul> <li>Causes hypocalcemia, leading to decreased bone mineralization</li> </ul><li>Produces fractures and bone pain</li> </ol><li>Osteoporosis (refer to <span macro="tag [[23 Musculoskeletal and Soft Tissue Disorders]] [[Chapter 23]]"></span>)</li><ol type="a"> <li>Loss of organic bone matrix and minerals</li><ul> <li>Causes an overall reduction in bone mass</li> </ul><li>In CRF, it is due to chronic metabolic acidosis.</li><ul> <li>Excess H<sup>+</sup> ions are buffered by bone.</li> </ul><li>Produces fractures and bone pain</li> </ol> </ol>
</div></html>
<html><a name="HC019042"></a> <br><a name="P019045"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hypertension from salt retention
<blockquote style="color: blue; ">CRF: hypertension, pericarditis, CHF, atherosclerosis</blockquote></li><li>Hemorrhagic fibrinous pericarditis</li><li>Congestive heart failure, accelerated atherosclerosis</li> </ol>
</div></html>
<html><a name="HC019043"></a> <br><a name="P019046"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hemorrhagic gastritis</li><li>Uremic frost (urea crystals deposit on skin)</li> </ol>
</div></html>
<html><a name="HC019044"></a> <br><a name="P019047"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acid-base and electrolyte abnormalities</li><ol type="a"> <li>Hyperkalemia and increased anion gap metabolic acidosis (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li><li>Sodium is usually normal <i>except</i> in salt-losing types of CRF.</li> </ol><li>Hypocalcemia; causes:</li><ol type="a"> <li>Hypovitaminosis D</li><ul> <li>(1) Due to decreased synthesis of 1-α-hydroxylase</li><li>(2) Decreased reabsorption of calcium from the small intestine
<blockquote style="color: blue; ">CRF: ↑ anion gap metabolic acidosis; ↑ serum phosphorus/potassium; ↓ serum calcium</blockquote></li> </ul><li>Hyperphosphatemia</li><ul> <li>(1) Due to decreased renal excretion</li><li>(2) Drives calcium into bone and soft tissue</li><ul> <li>Metastatic calcification (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li> </ul> </ul> </ol><li>Normocytic anemia; prolonged bleeding time</li><li>Increased serum cystatin C</li><ol type="a"> <li>Cysteine protease inhibitor produced by all nucleated cells
<blockquote style="color: blue; ">Cystatin C: biomarker of kidney function</blockquote></li><li>Filtered by glomerulus but <i>not</i> secreted</li><li>Less dependent on age, sex, race, and muscle mass than creatinine</li><li>May be superior to creatinine in assessing severity of renal function</li><ul> <li>Biomarker of kidney function</li> </ul> </ol><li>Urinalysis findings</li><ol type="a"> <li>Fixed specific gravity</li><ul> <li>(1) Tubular dysfunction causes lack of concentration and dilution.
<blockquote style="color: blue; ">Free water clearance in CRF: zero</blockquote></li><li>(2) Free water clearance is zero (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>).</li> </ul><li>Waxy/broad casts (see <span>[[Fig. 19-2H|Figure 19-2]]</span>)
<blockquote style="color: blue; ">Waxy casts: sign of CRF</blockquote></li> </ol> </ol>
</div></html>
<html><a name="HC019045"></a> <br><a name="P019048"></a><div class="PA" style="color: black; "><ol type="1"> <li>Nonpharmacologic</li><ol type="a"> <li>Restrict sodium</li><li>Low-protein diet (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>)</li><li>Adjust drug doses to renal clearance</li><li>Kidney transplantation</li> </ol><li>General</li><ol type="a"> <li>ACE inhibitors</li><ul> <li>(1) Reduce proteinuria and disease progression</li><li>(2) Treat hypertension</li> </ul><li>Dialysis</li><li>Erythropoiesis stimulating agents</li><li>Calcium supplementation and vitamin D (calcitriol)</li><ul> <li>Treat renal osteodystrophy</li> </ul><li>Phosphate binder (e.g., sevelamer)</li> </ol> </ol>
</div></html>
<html><a name="HC019053"></a> <br><a name="P019056"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Children usually have congenital malformation.</li><ul> <li>Examples-bladder neck obstruction; urethral valve</li> </ul><li>Adults usually have acquired disease.</li><ul> <li>Examples-stone (most common); prostate hyperplasia</li> </ul> </ol><li>Causes</li><ol type="a"> <li>Renal stone (most common)
<blockquote style="color: blue; ">Hydronephrosis: most common complication of upper urinary tract obstruction</blockquote></li><li>Retroperitoneal fibrosis</li><li>Cervical cancer, benign prostatic hyperplasia</li> </ol><li>Gross findings</li><ol type="a"> <li>Dilated ureter and renal pelvis (<span>[[Fig. 19-14|Figure 19-14]]</span>)</li><li>Compression atrophy of the renal medulla and cortex</li> </ol><li>May produce postrenal azotemia</li><li>Treatment is to relieve the obstruction.</li><ul> <li>Catheter (most often); nephrostomy tube; cystoscopy
<blockquote style="color: blue; ">Renal stone: most common cause of upper urinary tract obstruction</blockquote></li> </ul> </ol>
</div></html>
<html><a name="HC019054"></a> <br><a name="P019057"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Stones occur in males more often than females.</li><li>Incidence is greater during the summer.</li><ul> <li>Insufficient fluid intake</li> </ul> </ol><li>Causes</li><ol type="a"> <li>Hypercalciuria in the absence of hypercalcemia</li><ul> <li>(1) Most common metabolic abnormality</li><li>(2) Due to increased gastrointestinal reabsorption of calcium
<blockquote style="color: blue; ">Hypercalciuria: most common metabolic abnormality causing calcium stones</blockquote></li><ul> <li>Called absorptive hypercalciuria</li> </ul> </ul><li>Decreased urine volume concentrates the urine.</li><ul> <li>Hydration is essential in preventing stone formation.</li> </ul><li>Reduced urine citrate
<blockquote style="color: blue; ">Thiazides: increase reabsorption of calcium out of urine</blockquote></li><ul> <li>Citrate normally chelates calcium.</li> </ul><li>Primary HPTH (10% of cases)</li><li>Diets high in dairy products (contain phosphate) or oxalates</li><li>Urinary infections due to urease producers (e.g., <i>Proteus</i>)</li> </ol><li>Types of renal stones
<blockquote style="color: blue; ">Renal stone: calcium oxalate most common; calcium phosphate</blockquote></li><ol type="a"> <li>Calcium stones (∼80%)</li><ul> <li>(1) Calcium oxalate stone (>50%) is the most common type in adults.</li><ul> <li>Increased incidence in pure vegans and those with Crohn's disease</li> </ul><li>(2) Calcium phosphate stones (10-20%) are the most common type in children.</li><ul> <li>Associated with dairy products and distal renal tubular acidosis</li> </ul> </ul><li>Magnesium ammonium phosphate (MAP)
<blockquote style="color: blue; ">Struvite stone: MAP; urease producers; alkaline urine pH</blockquote></li><ul> <li>(1) "Staghorn calculus" or struvite stone (15%; <span>[[Fig. 19-15|Figure 19-15]]</span>)</li><li>(2) Associated with urease producers (e.g., <i>Proteus</i>)</li><li>(3) Urine is alkaline and smells like ammonia.</li> </ul><li>Uric acid (8%), cystine (3%)</li> </ol><li>Clinical findings</li><ol type="a"> <li>Sudden onset of flank tenderness
<blockquote style="color: blue; ">Renal stone: ipsilateral colicky pain in flank radiating to groin; hematuria</blockquote></li><li>Nausea and vomiting</li><li>Colicky pain radiating into groin</li><li>Patient constantly moving to try to relieve pain</li><li>Gross hematuria may be evident.</li> </ol><li>Laboratory findings</li><ol type="a"> <li>Hematuria</li><li>May find crystals in urine</li><li>Hypercalcemia</li><ul> <li>Consider primary HPTH</li> </ul> </ol><li>Diagnosis</li><ol type="a"> <li>Plain film (kidney-ureter-bladder [KUB])
<blockquote style="color: blue; ">Plain film: 80% stones radiopaque</blockquote></li><ul> <li>Approximately 80% of stones are radiopaque.</li> </ul><li>Unenhanced spiral (helical) CT
<blockquote style="color: blue; ">Spiral CT: best overall sensitivity and specificity; expensive</blockquote></li><ul> <li>Sensitivity 96%, specificity 100%</li> </ul><li>Ultrasound (sensitivity 15%, specificity 90%)</li><li>Strain urine to collect stone</li><ul> <li>(1) Always send for analysis
<blockquote style="color: blue; ">Ultrasound: detects hydronephrosis, not stone</blockquote></li><li>(2) Greater than 50% pass stone within 48 hours.</li><li>(3) Recurrence occurs in ∼50% of patients.
<blockquote style="color: blue; ">Stone prevention: hydration is very important</blockquote></li> </ul> </ol><li>Treatment is tailored to type of stone.</li><ol type="a"> <li>Calcium stone</li><ul> <li>(1) Hydrochlorothiazide
<blockquote style="color: blue; ">Rx for calcium stones: hydrochlorothiazide</blockquote></li><ul> <li>Increases renal tubule reabsorption of calcium (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li> </ul><li>(2) Cellulose phosphate</li><ul> <li>Binds calcium in intestine</li> </ul> </ul><li>Uric acid stone</li><ul> <li>(1) Allopurinol</li><li>(2) Increase urinary pH</li><ul> <li>Makes uric acid soluble in urine</li> </ul> </ul><li>Struvite stone</li><ul> <li>(1) Surgical removal because of size</li><li>(2) Antibiotic to eliminate urease producer</li> </ul><li>Surgical removal</li><ul> <li>(1) Extracorporeal shock wave lithotripsy</li><li>(2) Ureteroscopic stone extraction</li> </ul> </ol> </ol>
</div></html>
![[19.X.A.Hydronephrosis]]
<<tiddler [[19.X.A.Hydronephrosis]]>>
![[19.X.B.Renal stones (urolithiasis)]]
<<tiddler [[19.X.B.Renal stones (urolithiasis)]]>>
<html><a name="HC019056"></a> <br><a name="P019060"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hamartoma composed of blood vessels, smooth muscle, and adipose cells</li><li>Associated with tuberous sclerosis (refer to <span macro="tag [[25 Nervous System and Special Sensory Disorders]] [[Chapter 25]]"></span>)
<blockquote style="color: blue; ">Angiomyolipoma: hamartoma associated with tuberous sclerosis</blockquote></li><ol type="a"> <li>Mental retardation</li><li>Multisystem hamartomas</li> </ol> </ol>
</div></html>
<html><a name="HC019057"></a> <br><a name="P019061"></a><div class="PA" style="color: black; "><ul> <li>Alias Grawitz tumor, clear cell carcinoma, hypernephroma</li><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Sporadic (most common) and hereditary types</li><li>Occurs in men more frequently than women</li><ul> <li>Occurs in the sixth to seventh decades</li> </ul><li>Risk factors</li><ul> <li>(1) Smoking (most common)
<blockquote style="color: blue; ">Renal cell carcinoma: yellow tumor with renal vein invasion</blockquote></li><li>(2) Von Hippel-Lindau disease (VHL)</li><ul> <li>(a) Autosomal dominant</li><li>(b) Chromosome 3 relationship</li><li>(c) Hemangioblastomas of cerebellum and retina</li><li>(d) Bilateral renal cell carcinoma (50-60%)</li> </ul><li>(3) Adult polycystic kidney disease</li><li>(4) Obesity, asbestos exposure, exposure to lead</li><li>(5) Exposure to gasoline and petroleum products</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Cytogenetic abnormalities occur in sporadic and hereditary cancers</li><ul> <li>Translocations with loss of von Hippel-Lindau suppressor gene</li> </ul><li>Cancer derives from proximal tubule cells
<blockquote style="color: blue; ">Renal cell carcinoma: derives from proximal tubule cell</blockquote></li> </ol><li>Gross and microscopic findings</li><ol type="a"> <li>Clear cell carcinoma</li><ul> <li>(1) Most common type (70-80%)</li><li>(2) Most are sporadic.</li><ul> <li>Remainder are associated with VHL.</li> </ul><li>(3) Upper pole mass with cysts and hemorrhage (<span>[[Fig. 19-16|Figure 19-16]]</span>)</li><ul> <li>Tumor is a bright yellow mass larger than 3 cm (75-80%).</li> </ul><li>(4) Composed of clear cells that contain lipid and glycogen (<span>[[Fig. 19-17|Figure 19-17]]</span>)</li><li>(5) Tendency for renal vein invasion (15-20%)
<blockquote style="color: blue; ">Renal cell carcinoma: smoking most common cause</blockquote></li><ul> <li>Yellow tumor may invade inferior vena cava and extend to right side of heart.</li> </ul><li>(6) Metastasis</li><ul> <li>(a) Lungs are the most common site (50-60%)</li><ul> <li>Often hemorrhagic, "cannonball" appearance on radiographs</li> </ul><li>(b) Bone (lytic lesions; 30-40%)</li><li>(c) Regional nodes (15-30%)</li><li>(d) Hemorrhagic nodules in the skin
<blockquote style="color: blue; ">Renal cell carcinoma: invades renal vein; poor prognosis</blockquote></li><ul> <li>Due to increased vascularity in the tumor</li> </ul> </ul> </ul> </ol><li>Clinical findings
<blockquote style="color: blue; ">Triad: hematuria, flank pain, abdominal mass</blockquote></li><ol type="a"> <li>Hematuria (50-60%)</li><li>Abdominal mass (25-45%)</li><li>Flank pain (35-40%)</li><li>Hypertension (20-40%)</li><li>Triad-hematuria, abdominal mass, flank pain (5-10%)</li><li>Weight loss (30-35%)</li><li>Fever (5-15%)</li><li>Left-sided varicocele (2-3%; refer to <span macro="tag [[20 Lower Urinary Tract and Male Reproductive Disorders]] [[Chapter 20]]"></span>)</li><ul> <li>Relates to invasion of left renal vein blocking left spermatic vein drainage</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Elevated erythrocyte sedimentation rate (50-60%)</li><li>Normocytic anemia (20-40%)</li><li>Ectopic secretion of hormones
<blockquote style="color: blue; ">Renal cell carcinoma: ectopic secretion EPO and PTH-related peptide</blockquote></li><ul> <li>(1) Erythropoietin (EPO)</li><ul> <li>Produces secondary polycythemia (4%)</li> </ul><li>(2) PTH-related protein</li><ul> <li>Produces hypercalcemia (3-6%)</li> </ul> </ul> </ol><li>Diagnosis</li><ul> <li>Ultrasound; abdominal CT; MRI</li> </ul><li>Treatment is nephrectomy.</li><li>Prognosis</li><ol type="a"> <li>Characteristically has late metastases</li><ul> <li>May recur 10 to 20 years after the tumor has been removed</li> </ul><li>Average 5-year survival rate is 45% with metastasis.</li><ul> <li>Up to 70% of cases do not have metastasis.</li> </ul><li>Extension into the renal vein or through the renal capsule has a poor prognosis</li><ul> <li>10% to 15% 5-year survival rate</li> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC019058"></a> <br><a name="P019062"></a><div class="PA" style="color: black; "><ol type="1"> <li>Transitional cell carcinoma (TCC)</li><ol type="a"> <li>Most common type</li><ul> <li>Approximately 50% have similar tumors elsewhere in the urinary tract.</li> </ul><li>Risk factors
<blockquote style="color: blue; ">TCC renal pelvis: smoking most common cause</blockquote></li><ul> <li>(1) Smoking (most common)</li><li>(2) Phenacetin abuse</li><li>(3) Aromatic amines (aniline dyes)</li><li>(4) Cyclophosphamide</li> </ul> </ol><li>Squamous cell carcinoma</li><ul> <li>Risk factors include renal stones and chronic infection.</li> </ul> </ol>
</div></html>
<html><a name="HC019059"></a> <br><a name="P019063"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Accounts for ∼5% of childhood cancer</li><li>Most common primary renal tumor in children
<blockquote style="color: blue; ">Wilms' tumor: most common primary renal tumor in children</blockquote></li><li>Occurs between 2 and 5 years of age</li><li>Sporadic type (most common)</li><li>Genetic type</li><ul> <li>(1) Autosomal dominant inheritance (chromosome 11)</li><li>(2) WAGR syndrome</li><ul> <li><i>W</i>ilms' tumor, <i>a</i>niridia (absent iris), <i>g</i>enital abnormalities, <i>r</i>etardation</li> </ul><li>(3) Beckwith-Wiedemann syndrome</li><ul> <li>Wilms' tumor, enlarged body organs, hemihypertrophy of extremities</li> </ul> </ul> </ol><li>Large, necrotic, gray-tan tumor</li><ol type="a"> <li>Derived from mesonephric mesoderm</li><li>Contains abortive glomeruli and tubules, primitive blastemal cells, and rhabdomyoblasts
<blockquote style="color: blue; ">Wilms' tumor: child with unilateral flank mass and hypertension</blockquote></li> </ol><li>Clinical findings</li><ol type="a"> <li>Unilateral palpable mass in a child with hypertension</li><ul> <li>Hypertension due to renin secretion
<blockquote style="color: blue; ">Wilms' tumor: hypertension due to renin secretion</blockquote></li> </ul><li>Lungs are the most common site of metastasis.</li><li>With combined therapies 2-year survival rate is >90%.</li> </ol> </ol>
</div></html>
![[19.XI.A.Angiomyolipoma]]
<<tiddler [[19.XI.A.Angiomyolipoma]]>>
![[19.XI.B.Renal cell carcinoma]]
<<tiddler [[19.XI.B.Renal cell carcinoma]]>>
![[19.XI.C.Renal pelvic cancer]]
<<tiddler [[19.XI.C.Renal pelvic cancer]]>>
![[19.XI.D.Wilms' tumor]]
<<tiddler [[19.XI.D.Wilms' tumor]]>>
<html><a name="HC002002"></a> <br><a name="P002002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Transient and early response to injury</li><li>Involves release of chemical mediators</li><li>Leads to stereotypic vessel and leukocyte responses
<blockquote style="color: blue; ">AI: not synonymous with infection</blockquote></li><li><i>Not</i> a synonym for infection</li> </ol>
</div></html>
![[2.I.A.Definition]]
<<tiddler [[2.I.A.Definition]]>>
![[2.I.B.Cardinal signs of inflammation (Fig. 2-1)]]
<<tiddler [[2.I.B.Cardinal signs of inflammation (Fig. 2-1)]]>>
![[2.I.C.Stimuli for acute inflammation]]
<<tiddler [[2.I.C.Stimuli for acute inflammation]]>>
![[2.I.D.Sequential vascular events]]
<<tiddler [[2.I.D.Sequential vascular events]]>>
![[2.I.E.Sequential cellular events (Fig. 2-2)]]
<<tiddler [[2.I.E.Sequential cellular events (Fig. 2-2)]]>>
![[2.I.F.Chemical mediators (Table 2-1)]]
<<tiddler [[2.I.F.Chemical mediators (Table 2-1)]]>>
![[2.I.G.Types of acute inflammation]]
<<tiddler [[2.I.G.Types of acute inflammation]]>>
![[2.I.H.Role of fever in inflammation]]
<<tiddler [[2.I.H.Role of fever in inflammation]]>>
![[2.I.I.Factors involved in the termination of acute inflammation]]
<<tiddler [[2.I.I.Factors involved in the termination of acute inflammation]]>>
![[2.I.J.Consequences of acute inflammation]]
<<tiddler [[2.I.J.Consequences of acute inflammation]]>>
<html><a name="HC002003"></a><span>[[Fig. 2-1|Figure 2-1]]</span> <br> <br><a name="P002003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Rubor (redness) and calor (heat)</li><ul> <li>Histamine-mediated vasodilation of arterioles</li> </ul><li>Tumor (swelling)</li><ol type="a"> <li>Histamine-mediated increase in permeability of venules</li><li>Synonymous with edema</li><ul> <li>Increased fluid in the interstitial space
<blockquote style="color: blue; ">Rubor, calor, tumor: histamine-mediated</blockquote></li> </ul> </ol><li>Dolor (pain)</li><ul> <li>Prostaglandin (PG) E<sub>2</sub> sensitizes specialized nerve endings to the effects of bradykinin and other pain mediators.</li> </ul><li>Functio laesa (loss of function)</li> </ol>
</div></html>
<html><a name="HC002004"></a> <br><a name="P002004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Infections (e.g., bacterial or viral infection)</li><li>Immune reactions (e.g., reaction to a bee sting)</li><li>Other stimuli</li><ul> <li>Tissue necrosis (e.g., acute myocardial infarction), trauma, radiation, burns, foreign body (e.g., glass, splinter)</li> </ul> </ol>
</div></html>
<html><a name="HC002005"></a> <br><a name="P002005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Vasoconstriction of arterioles</li><ul> <li>Neurogenic reflex that lasts only seconds</li> </ul><li>Vasodilation of arterioles</li><ol type="a"> <li>Histamine and other vasodilators (e.g., nitric oxide) relax vascular smooth muscle, causing increased blood flow.</li><li>Increased blood flow increases hydrostatic pressure.</li> </ol><li>Increased permeability of venules
<blockquote style="color: blue; ">Mast cells: release preformed histamine</blockquote></li><ol type="a"> <li>Histamine and other mediators contract endothelial cells producing endothelial gaps.</li><ul> <li>Tight junctions are simpler in venules than arterioles.</li> </ul><li>A transudate (protein and cell-poor fluid) moves into the interstitial tissue.</li> </ol><li>Swelling of tissue (tumor, edema)</li><ul> <li>Net outflow of fluid surpasses lymphatic ability to remove fluid.</li> </ul><li>Reduced blood flow</li><ul> <li>Decrease in hydrostatic pressure caused by outflow of fluid into the interstitial tissue</li> </ul> </ol>
</div></html>
<html><a name="HC002006"></a><span>[[Fig. 2-2|Figure 2-2]]</span> <br> <br><a name="PB002001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Chronic granulomatous disease (CGD)</b> is an X-linked recessive (XR) disorder (65% of cases) or autosomal recessive disorder (35% of cases). The X-linked type is characterized by deficient NADPH oxidase in the cell membranes of neutrophils and monocytes. The reduced production of <br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-002-i001.jpg" id=""> results in an absent respiratory burst. Catalase-positive organisms that produce H<sub>2</sub>O<sub>2</sub> (e.g., <i>Staphylococcus aureus</i>) are ingested but <i>not</i> killed, because the catalase degrades H<sub>2</sub>O<sub>2</sub>. Myeloperoxidase is present, but HOCl<sup>•</sup> is <i>not</i> synthesized because of the absence of H<sub>2</sub>O<sub>2</sub>. Catalase-negative organisms (e.g., <i>Streptococcus</i> species) are ingested and killed when myeloperoxidase combines H<sub>2</sub>O<sub>2</sub> with Cl to form HOCl<sup>•</sup>. Granulomatous inflammation occurs in tissue, because the neutrophils, which can phagocytose bacteria but not kill most of them, are eventually replaced by cells associated with chronic inflammation, mainly lymphocytes and macrophages. Macrophages fuse together to form multinucleated giant cells. Patients have severe infections involving lungs, skin, visceral organs, and bones. The classic screening test for CGD is the nitroblue tetrazolium (NBT) test. In this test, leukocytes are incubated with a colorless NBT dye, which is converted to a blue color if the respiratory burst is intact. This test has been replaced by a more sensitive test involving oxidation of dihydrorhodamine to fluorescent rhodamine. Bone marrow transplantation is the treatment of choice for the XR type of CGD.</div><a name="PB002002"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Myeloperoxidase (MPO) deficiency</b>, an autosomal recessive disorder, differs from CGD in that both <br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-002-i001.jpg" id=""> and H<sub>2</sub>O<sub>2</sub> are produced (normal respiratory burst). However, the absence of MPO prevents synthesis of HOCl<sup>•</sup>.</div><a name="P002006"></a><div class="PA" style="color: black; "><ul> <li>The events described will emphasize neutrophil events in acute inflammation due to a bacterial infection (e.g., <i>Staphylococcus aureus</i>).
<blockquote style="color: blue; ">Neutrophils: primary leukocytes in acute inflammation</blockquote></li><ol type="1"> <li>Neutrophils are the primary leukocytes in acute inflammation (<span>[[Fig. 2-3|Figure 2-3]]</span>).</li><li>Margination</li><ol type="a"> <li>RBCs aggregate into rouleaux ("stacks of coins") in venules.</li><li>Neutrophils are pushed from the central axial column to the periphery (margination).</li> </ol><li>Rolling</li><ol type="a"> <li>Due to activation of selectin adhesion molecules on the surface of neutrophils and endothelial cells
<blockquote style="color: blue; ">Selectins: responsible for "rolling" of neutrophils</blockquote></li><li>Neutrophils loosely bind to selectins and "roll" along the endothelium.</li> </ol><li>Adhesion</li><ol type="a"> <li>Adhesion molecules firmly bind neutrophils to endothelial cells.</li><ul> <li>(1) Neutrophils in the peripheral blood are subdivided into a circulating pool and a marginating pool (already attached to endothelial cells).</li><li>(2) Normally, ∼50% of peripheral blood neutrophils are in the circulating pool and ∼50% in the marginating pool.</li><li>(3) This distribution can be altered by activating or inactivating neutrophil adhesion molecules (see later).</li> </ul><li>Neutrophil adhesion molecules</li><ul> <li>(1) β<sub>2</sub>-Integrins (CD11a:CD18)
<blockquote style="color: blue; ">β<sub>2</sub>-Integrins: neutrophil adhesion molecules</blockquote></li><li>(2) Adhesion molecule activation is mediated by C5a and leukotriene B<sub>4</sub> (LTB<sub>4</sub>).</li><li>(3) Catecholamines, corticosteroids, and lithium inhibit activation of adhesion molecules.
<blockquote style="color: blue; ">Neutrophil leukocytosis: catecholamines, corticosteroids, lithium</blockquote></li><ul> <li>(a) Peripheral blood neutrophil count (neutrophilic leukocytosis) is increased.</li><li>(b) Normal marginating pool is now part of the circulating pool.</li> </ul><li>(4) Endotoxins enhance activation of adhesion molecules.</li><ul> <li>(a) Peripheral blood neutrophil count (neutropenia) is decreased.</li><li>(b) Normal circulating pool is now part of the marginating pool.
<blockquote style="color: blue; ">Neutropenia: endotoxins</blockquote></li> </ul> </ul><li>Endothelial cell adhesion molecules</li><ul> <li>(1) Intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) bind to integrins on the surface of neutrophils.</li><li>(2) ICAM and VCAM activation is mediated by interleukin 1 (IL-1) and tumor necrosis factor (TNF).</li> </ul><li>Leukocyte adhesion deficiency (LAD)</li><ul> <li>(1) Autosomal recessive disorders</li><li>(2) LAD type 1 is a deficiency of CD11a:CD18.</li><li>(3) LAD type 2 is a deficiency of a selectin that binds neutrophils.</li><li>(4) Clinical findings</li><ul> <li>(a) Delayed separation of the umbilical cord (∼1 month)
<blockquote style="color: blue; ">Delayed separation umbilical cord: selectin or CD11a:CD18 deficiency</blockquote></li><ul> <li>Neutrophil enzymes are important in cord separation.</li> </ul><li>(b) Severe gingivitis, poor wound healing, peripheral blood neutrophilic leukocytosis (loss of marginating pool)</li> </ul> </ul> </ol><li>Transmigration (diapedesis)</li><ol type="a"> <li>Neutrophils dissolve the basement membrane and enter interstitial tissue.</li><li>Fluid rich in proteins and cells (i.e., exudate) accumulates in interstitial tissue.</li><li>Functions of exudate</li><ul> <li>(1) Dilutes bacterial toxins</li><li>(2) Provides opsonins (IgG, C3b) to assist in phagocytosis</li> </ul> </ol><li>Chemotaxis
<blockquote style="color: blue; ">Chemotaxis: directed migration of neutrophils</blockquote></li><ol type="a"> <li>Neutrophils follow chemical gradients that lead to the infection site.</li><li>Chemotactic mediators bind to neutrophil receptors.</li><ul> <li>Mediators include C5a, LTB<sub>4</sub>, bacterial products, and interleukin (IL) 8.</li> </ul><li>Binding causes the release of calcium, which increases neutrophil motility.</li> </ol><li>Phagocytosis</li><ol type="a"> <li>Multistep process, consisting of three steps</li><ul> <li>(1) Opsonization</li><li>(2) Ingestion</li><li>(3) Killing</li> </ul><li>Opsonization</li><ul> <li>(1) Opsonins attach to bacteria (or foreign bodies).
<blockquote style="color: blue; ">Opsonins: IgG and C3b</blockquote></li><ul> <li>(a) Opsonins include IgG, C3b fragment of complement, and other proteins (e.g., C-reactive protein).</li><li>(b) Neutrophils have membrane receptors for IgG and C3b.</li> </ul><li>(2) Opsonization enhances neutrophil recognition and attachment to bacteria.</li><li>(3) Bruton's agammaglobulinemia is an opsonization defect.
<blockquote style="color: blue; ">Bruton's agammaglobulinemia: opsonization defect</blockquote></li> </ul><li>Ingestion</li><ul> <li>(1) Neutrophils engulf (phagocytose) and then trap bacteria in phagocytic vacuoles.</li><li>(2) Primary lysosomes empty hydrolytic enzymes into phagocytic vacuoles producing phagolysosomes.</li><ul> <li>In Chédiak-Higashi syndrome (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>), a defect in microtubule function prevents phagolysosome formation.
<blockquote style="color: blue; ">Chédiak-Higashi syndrome: cannot form phagolysosomes</blockquote></li> </ul> </ul><li>Bacterial killing</li><ul> <li>(1) O<sub>2</sub>-dependent myeloperoxidase (MPO) system (<span>[[Fig. 2-4|Figure 2-4]]</span>)
<blockquote style="color: blue; ">O<sub>2</sub>-dependent MPO system: most potent microbicidal system</blockquote></li><ul> <li>(a) Only present in neutrophils and monocytes (<i>not</i> macrophages)</li><li>(b) Production of superoxide free radicals (<br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-002-i001.jpg" id="">)</li><ul> <li>Reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase converts molecular O<sub>2</sub> to <br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-002-i001.jpg" id="">, which releases energy called the respiratory, or oxidative, burst.</li> </ul><li>(c) Production of peroxide (H<sub>2</sub>O<sub>2</sub>)
<blockquote style="color: blue; ">End-product O<sub>2</sub>-dependent MPO system: bleach</blockquote></li><ul> <li>Superoxide dismutase converts <br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-002-i001.jpg" id=""> to H<sub>2</sub>O<sub>2</sub>, which is neutralized by glutathione peroxidase.</li> </ul><li>(d) Some peroxide is converted to hydroxyl free radicals by iron.</li><li>(e) Production of bleach (HOCl<sup>•</sup>)</li><ul> <li>MPO combines H<sub>2</sub>O<sub>2</sub> with chloride (Cl<sup>-</sup>) to form hypochlorous free radicals (HOCl<sup>•</sup>), which kill bacteria.</li> </ul><li>(f) Chronic granulomatous disease and MPO deficiency are examples of diseases that have a defect in the O<sub>2</sub>-dependent MPO system.
<blockquote style="color: blue; ">Chronic granulomatous disease: absent NADPH oxidase and respiratory burst</blockquote></li><li>(g) Deficiency of NADPH (e.g., glucose-6-phosphate dehydrogenase deficiency) produces a microbicidal defect.
<blockquote style="color: blue; ">MPO deficiency: normal respiratory burst</blockquote></li> </ul><li>(2) O<sub>2</sub>-independent system</li><ul> <li>(a) Refers to bacterial killing from substances located in leukocyte granules</li><li>(b) Examples-lactoferrin (binds iron necessary for bacterial reproduction) and major basic protein (eosinophil product that is cytotoxic to helminths)</li> </ul> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC002007"></a><span>[[Table 2-1|Table 2-1. SOURCES AND FUNCTIONS OF CHEMICAL MEDIATORS]]</span> <br> <br><a name="P002007"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Histamine: most important chemical mediator of acute inflammation</blockquote>
<ol type="1"> <li>They derive from plasma, leukocytes, local tissue, bacterial products.</li><ul> <li>Example-arachidonic acid mediators are released from membrane phospholipids in macrophages, endothelial cells, and platelets (<span>[[Fig. 2-5|Figure 2-5]]</span>).</li> </ul><li>They have short half-lives (e.g., seconds to minutes).
<blockquote style="color: blue; ">Chemical mediators: short half-lives</blockquote></li><li>They may have local and systemic effects.</li><ul> <li>Example-histamine may produce local signs of itching or systemic signs of anaphylaxis.</li> </ul><li>They have diverse functions.</li><ol type="a"> <li>Vasodilation</li><ul> <li>Examples-histamine, nitric oxide, PGI<sub>2</sub></li> </ul><li>Vasoconstriction</li><ul> <li>Example-thromboxane A<sub>2</sub> (TXA<sub>2</sub>)</li> </ul><li>Increase vessel permeability</li><ul> <li>Examples-histamine, bradykinin, LTC<sub>4</sub>-D<sub>4</sub>-E<sub>4</sub>, C3a and C5a (anaphylatoxins)</li> </ul><li>Produce pain</li><ul> <li>Examples-PGE<sub>2</sub>, bradykinin</li> </ul><li>Produce fever</li><ul> <li>Examples-PGE<sub>2</sub>, IL-1, TNF</li> </ul><li>Chemotactic</li><ul> <li>Examples-C5a, LTB<sub>4</sub>, IL-8</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC002008"></a> <br><a name="P002008"></a><div class="PA" style="color: black; "><ul> <li>Location, cause, and duration of inflammation determine the morphology of an inflammatory reaction.</li><ol type="1"> <li>Purulent (suppurative) inflammation</li><ol type="a"> <li>Localized proliferation of pus-forming organisms, such as <i>Staphylococcus aureus</i> (e.g., skin abscess; <span>[[Fig. 2-6|Figure 2-6]]</span>)</li><li><i>S. aureus</i> contains coagulase, which cleaves fibrinogen into fibrin and traps bacteria and neutrophils.
<blockquote style="color: blue; "><i>S. aureus</i> : most common cause of a skin abscess</blockquote></li> </ol><li>Fibrinous inflammation</li><ol type="a"> <li>Due to increased vessel permeability, with deposition of a fibrin-rich exudate</li><li>Often occurs on the serosal lining of the pericardium, peritoneum, or pleura</li><ul> <li>Danger of adhesions</li> </ul><li>Example-fibrinous pericarditis (<span>[[Fig. 2-7|Figure 2-7]]</span>)</li> </ol><li>Serous inflammation</li><ol type="a"> <li>Thin, watery exudate</li><ul> <li>Insufficient amount of fibrinogen to produce fibrin</li> </ul><li>Examples-blister in second-degree burns, viral pleuritis</li> </ol><li>Pseudomembranous inflammation
<blockquote style="color: blue; ">Pseudomembranous inflammation: diphtheria, <i>Clostridium difficile;</i> noninvasive bacteria</blockquote></li><ol type="a"> <li>Bacterial toxin-induced damage of the mucosal lining, producing a shaggy membrane composed of necrotic tissue</li><li>Example-pseudomembranes associated with <i>Clostridium difficile</i> in pseudomembranous colitis (<span>[[Fig. 2-8|Figure 2-8]]</span>)</li><ul> <li><i>Corynebacterium diphtheriae</i> produces a toxin causing pseudomembrane formation in the pharynx and trachea.</li> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC002009"></a> <br><a name="P002009"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Fever is good!</blockquote>
<ol type="1"> <li>Right-shifts oxygen-binding curve</li><ul> <li>More O<sub>2</sub> is available for the O<sub>2</sub>-dependent MPO system.</li> </ul><li>Provides a hostile environment for bacterial and viral reproduction</li> </ol>
</div></html>
<html><a name="HC002010"></a> <br><a name="P002010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Short half-life of inflammatory mediators</li><li>Lipoxins</li><ol type="a"> <li>Anti-inflammatory mediators</li><li>Derive from arachidonic acid metabolites (e.g., LXA<sub>4</sub>, LXB<sub>4</sub>)</li><li>Inhibit transmigration and chemotaxis</li><li>Signal macrophages to phagocytose apoptotic bodies</li> </ol><li>Resolvins</li><ol type="a"> <li>Synthesized from omega-3 fatty acids</li><li>Inhibit production and recruitment of inflammatory cells to the site of inflammation
<blockquote style="color: blue; ">Clearance of neutrophils in AI: apoptosis</blockquote></li> </ol><li>Clearance of neutrophils by apoptosis</li> </ol>
</div></html>
<html><a name="HC002011"></a> <br><a name="P002011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Complete resolution</li><ol type="a"> <li>Occurs with mild injury to cells that have the capacity to enter the cell cycle (e.g., labile and stable cells)</li><li>Examples-first-degree burn, bee sting</li> </ol><li>Tissue destruction and scar formation</li><ol type="a"> <li>Occurs with extensive injury or damage to permanent cells</li><li>Example-third-degree burns</li> </ol><li>Formation of abscesses</li><ul> <li>Example-lung abscess in bronchopneumonia</li> </ul><li>Progression to chronic inflammation</li> </ol>
</div></html>
<html><a name="HC002013"></a> <br><a name="P002020"></a><div class="PA" style="color: black; "><ul> <li>Inflammation of prolonged duration (weeks to years) that most often results from persistence of an injury-causing agent</li> </ul>
</div></html>
<html><a name="HC002014"></a> <br><a name="P002021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Infection
<blockquote style="color: blue; ">Infection: most common cause of chronic inflammation</blockquote></li><ul> <li>Examples-tuberculosis, leprosy, hepatitis C</li> </ul><li>Autoimmune disease</li><ul> <li>Examples-rheumatoid arthritis, systemic lupus erythematosus</li> </ul><li>Sterile agents
<blockquote style="color: blue; ">Monocytes and macrophages: primary leukocytes in chronic inflammation</blockquote></li><ul> <li>Examples-silica, uric acid, silicone in breast implants</li> </ul> </ol>
</div></html>
<html><a name="HC002015"></a> <br><a name="P002022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Cell types</li><ul> <li>Monocytes and macrophages (key cells), lymphocytes and plasma cells, eosinophils (<span>[[Fig. 2-9|Figure 2-9]]</span>)</li> </ul><li>Necrosis</li><ul> <li><i>Not</i> as prominent a feature as in acute inflammation</li> </ul><li>Destruction of parenchyma</li><ul> <li>Loss of functional tissue, with repair by fibrosis</li> </ul><li>Formation of granulation tissue</li><ol type="a"> <li>Highly vascular tissue composed of blood vessels and activated fibroblasts</li><ul> <li>(1) Blood vessels derive from preexisting blood vessels (i.e., angiogenesis)</li><li>(2) Essential for normal wound healing</li><li>(3) Precursor for scar tissue
<blockquote style="color: blue; ">Granulation tissue: converted to scar tissue</blockquote></li> </ul><li>Fibronectin is required for granulation tissue formation.</li><ul> <li>(1) Cell adhesion glycoprotein located in the extracellular matrix (ECM)</li><ul> <li>Binds to collagen, fibrin, and cell surface receptors (e.g., integrins)</li> </ul><li>(2) Chemotactic factor that attracts fibroblasts (synthesize collagen) and endothelial cells (form new blood vessels, angiogenesis)
<blockquote style="color: blue; ">Fibronectin: key adhesion glycoprotein in ECM</blockquote></li><ul> <li>Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF) are important in angiogenesis.</li> </ul> </ul> </ol><li>Comparison of acute and chronic inflammation (<span>[[Table 2-2|Table 2-2. COMPARISON OF ACUTE AND CHRONIC INFLAMMATION]]</span>)</li><li>Granulomatous inflammation</li><ol type="a"> <li>Specialized type of chronic inflammation</li><li>Causes</li><ul> <li>(1) Infections</li><ul> <li>(a) Examples-tuberculosis and systemic fungal infection (e.g., histoplasmosis)</li><li>(b) Usually associated with caseous necrosis (i.e., soft granulomas)</li><ul> <li>Caseation is due to lipid released from the cell wall of dead pathogens.</li> </ul> </ul><li>(2) Noninfectious causes</li><ul> <li>(a) Examples-sarcoidosis and Crohn's disease</li><li>(b) Noncaseating (i.e., hard granulomas)</li> </ul> </ul><li>Morphology</li><ul> <li>(1) Pale, white nodule with or without central caseation</li><li>(2) Usually well-circumscribed (see <span>[[Fig. 1-11G|Figure 1-11]]</span>)
<blockquote style="color: blue; ">Cell types in tuberculous granuloma: macrophages and CD4 helper T cells</blockquote></li><li>(3) Cell types</li><ul> <li>(a) Epithelioid cells (activated macrophages), mononuclear (round cell) infiltrate (CD4 helper T cells, or T<sub>H</sub> cells of the T<sub>H</sub>1 type)
<blockquote style="color: blue; ">Epithelioid cells: macrophages activated by γ-interferon from CD4 T<sub>H</sub> cells</blockquote></li><li>(b) Multinucleated giant cells formed by fusion of epithelioid cells</li><ul> <li>Nuclei usually located at the periphery</li> </ul> </ul><li>(4) TNF-α is important in the formation and maintenance of tuberculous and systemic fungal granulomas.</li><ul> <li>(a) TNF-α and γ-interferon recruit cells for granuloma formation (see later).
<blockquote style="color: blue; ">TNF-α important in formation and maintenance of granulomas</blockquote></li><li>(b) TNF-α inhibitors cause the breakdown of granulomas leading to dissemination of disease.</li> </ul><li>(5) Pathogenesis of a tuberculous granuloma (<span>[[Box 2-1|BOX 2-1 SEQUENCE OF FORMATION OF A TUBERCULOUS GRANULOMA]]</span>)</li> </ul> </ol> </ol>
</div></html>
![[2.II.A.Definition]]
<<tiddler [[2.II.A.Definition]]>>
![[2.II.B.Causes of chronic inflammation]]
<<tiddler [[2.II.B.Causes of chronic inflammation]]>>
![[2.II.C.Morphology]]
<<tiddler [[2.II.C.Morphology]]>>
<html><a name="HC002017"></a> <br><a name="P002025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Parenchymal cell regeneration</li><li>Repair by connective tissue (fibrosis)</li> </ol>
</div></html>
<html><a name="HC002018"></a> <br><a name="P002026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Depends on the ability of cells to replicate</li><ol type="a"> <li>Labile cells (e.g., stem cells in epidermis) and stable cells (e.g., fibroblasts) can replicate (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>).</li><li>Permanent cells <i>cannot</i> replicate.</li><ul> <li>Cardiac and striated muscle are replaced by scar tissue (fibrosis).</li> </ul> </ol><li>Depends on factors that stimulate parenchymal cell division and migration</li><ul> <li>Stimulatory factors include loss of tissue and production of growth factors (<span>[[Table 2-3|Table 2-3. FACTORS INVOLVED IN TISSUE REPAIR]]</span>).</li> </ul><li>Cell cycle (<span>[[Fig. 2-10|Figure 2-10]]</span>)</li><ol type="a"> <li>Phases of the cell cycle</li><ul> <li>(1) G<sub>0</sub> phase</li><ul> <li>Resting phase of stable parenchymal cells</li> </ul><li>(2) G<sub>1</sub> phase
<blockquote style="color: blue; ">G<sub>1</sub> phase: most variable phase in cell cycle</blockquote></li><ul> <li>Synthesis of RNA, protein, organelles, and cyclin D</li> </ul><li>(3) S (synthesis) phase</li><ul> <li>Synthesis of DNA, RNA, protein</li> </ul><li>(4) G<sub>2</sub> phase</li><ul> <li>Synthesis of tubulin, which is necessary for formation of the mitotic spindle</li> </ul><li>(5) M (mitotic) phase</li><ul> <li>Two daughter cells are produced.</li> </ul> </ul><li>Regulation of the G<sub>1</sub> checkpoint (G<sub>1</sub> to S phase)</li><ul> <li>(1) Most critical phase of the cell cycle
<blockquote style="color: blue; ">G<sub>1</sub> to S phase: most critical phase in cell cycle</blockquote></li><li>(2) Control proteins include cyclin-dependent kinase 4 (Cdk4) and cyclin D</li><ul> <li>(a) Growth factors activate nuclear transcribing proto-oncogenes to produce cyclin D and Cdk4.</li><li>(b) Cyclin D binds to Cdk4, forming a complex causing the cell to enter the S phase.</li> </ul><li>(3) <i>RB</i> (retinoblastoma) suppressor gene</li><ul> <li>(a) RB protein product arrests the cell in the G<sub>1</sub> phase.</li><li>(b) Cdk4 phosphorylates the RB protein causing the cell to enter the S phase.
<blockquote style="color: blue; ">Genes controlling G<sub>1</sub> to S phase: <i>RB</i> and <i>TP53</i> suppressor genes</blockquote></li> </ul><li>(4) <i>TP53</i> suppressor gene</li><ul> <li>(a) TP53 protein product arrests the cell in the G<sub>1</sub> phase by inhibiting Cdk4.</li><ul> <li>Prevents RB protein phosphorylation and, if necessary, provides time for repair of DNA in the cell</li> </ul><li>(b) In the event that there is excessive DNA damage, the <i>BAX</i> gene is activated.</li><ul> <li><i>BAX</i> gene inhibits the <i>BCL2</i> antiapoptosis gene (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>) causing release of cytochrome <i>c</i> from the mitochondria and apoptosis of the cell.
<blockquote style="color: blue; "><i>BAX</i> gene: activation by <i>TP53</i> initiates apoptosis</blockquote></li> </ul> </ul> </ul> </ol><li>Restoration to normal</li><ol type="a"> <li>Requires preservation of the basement membrane</li><li>Requires a relatively intact ECM (i.e., collagen, adhesive proteins)</li><ul> <li>Laminin, the key adhesion protein in the basement membrane, interacts with type IV collagen, cell surface receptors, and components in the ECM.
<blockquote style="color: blue; ">Laminin: key adhesion glycoprotein in basement membrane</blockquote></li> </ul> </ol> </ol>
</div></html>
<html><a name="HC002019"></a> <br><a name="PB002003"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Ehlers-Danlos syndrome (EDS)</b> consists of a group of mendelian disorders characterized by defects of type I and type III collagen synthesis and structure. Clinical findings include hypermobile joints, aortic dissection (most common cause of death), bleeding into the skin (ecchymoses), rupture of the bowel, and poor wound healing (<span>[[Fig. 2-11|Figure 2-11]]</span>).</div><a name="P002027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Occurs when injury is severe or persistent</li><ul> <li>Tissue in a third-degree burn <i>cannot</i> be restored to normal owing to loss of skin, basement membrane, and connective tissue infrastructure.</li> </ul><li>Steps in repair</li><ol type="a"> <li>Requires neutrophil transmigration to liquefy injured tissue and then macrophage transmigration to remove the debris</li><li>Requires formation of granulation tissue
<blockquote style="color: blue; ">Granulation tissue: essential for normal connective tissue repair.</blockquote></li><ul> <li>Accumulates in the ECM and eventually produces dense fibrotic tissue (scar)</li> </ul><li>Requires the initial production of type III collagen</li><ul> <li>(1) Collagen is the major fibrous component of connective tissue.</li><li>(2) Tropocollagen, the structural unit of collagen, is a triple helix of α-chains.
<blockquote style="color: blue; ">Lysyl oxidase: cross-links ↑ tensile strength</blockquote></li><ul> <li>(a) Tropocollagen undergoes extensive posttranslational modification.</li><li>(b) Hydroxylation reactions in the rough endoplasmic reticulum convert proline to hydroxyproline and lysine to hydroxylysine.</li><ul> <li>Ascorbic acid is required in these hydroxylation reactions.
<blockquote style="color: blue; ">Ascorbic acid: hydroxylates proline and lysine</blockquote></li> </ul><li>(c) Hydroxyproline residues produce bonds that stabilize the triple helix in the tropocollagen molecule.</li><li>(d) Hydroxylysine residues are oxidized to form an aldehyde residue that produces covalent cross-links at staggered intervals between adjacent tropocollagen molecules.
<blockquote style="color: blue; ">Copper: cofactor in lysyl oxidase</blockquote></li><ul> <li>Lysyl oxidase is a metalloproteinase enzyme containing copper.</li> </ul><li>(e) Cross-linking increases the overall tensile strength of collagen (also elastic tissue).</li><ul> <li>Type I collagen in skin, bone, and tendons has the greatest tensile strength.</li> </ul><li>(f) Cross-linking increases with age.</li><ul> <li>This leads to decreased elasticity of skin, joints, and blood vessels.</li> </ul><li>(g) Decreased cross-linking (e.g., vitamin C deficiency) reduces the tensile strength of collagen.</li><ul> <li>In vitamin C deficiency, the structurally weakened collagen is responsible for a bleeding diathesis (e.g., bleeding into skin and joints) and poor wound healing (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>).
<blockquote style="color: blue; ">EDS: defects in type I and III collagen</blockquote></li> </ul> </ul> </ul><li>Dense scar tissue produced from granulation tissue must be remodeled.</li><ul> <li>(1) Remodeling increases the tensile strength of scar tissue.
<blockquote style="color: blue; ">Zinc: cofactor in collagenase</blockquote></li><li>(2) Metalloproteinases (collagenases) replace type III collagen with type I collagen, increasing tensile strength to approximately 80% of the original.</li> </ul> </ol><li>Primary and secondary intention wound healing (<span>[[Box 2-2|BOX 2-2 WOUND HEALING BY PRIMARY AND SECONDARY INTENTION]]</span>)</li><ol type="a"> <li>Healing by primary intention</li><ul> <li>(1) Approximation of wound edges by sutures</li><li>(2) Used for clean surgical wounds</li> </ul><li>Healing by secondary intention</li><ul> <li>(1) Wound remains open</li><li>(2) Used for gaping or infected wounds</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC002020"></a> <br><a name="P002028"></a><div class="PA" style="color: black; "><ol type="1"> <li>Persistent infection</li><ol type="a"> <li>Most common cause of impaired wound healing
<blockquote style="color: blue; ">Infections: most common cause of impaired wound healing</blockquote></li><li><i>Staphylococcus aureus</i> is the most common pathogen.</li><li>Nosocomial and community-acquired methicillin-resistant <i>Staphylococcus aureus</i> wound infections are increasing.</li><ul> <li>(1) Vancomycin is used for treating nosocomial infections.</li><li>(2) Trimethoprim-sulfamethoxazole is used for treating community acquired infections.</li> </ul> </ol><li>Metabolic disorders</li><ul> <li>Example-diabetes mellitus increases susceptibility to infection by decreasing blood flow to tissue and increasing tissue levels of glucose.</li> </ul><li>Nutritional deficiencies</li><ol type="a"> <li>Decreased protein (e.g., malnutrition)</li><li>Vitamin C deficiency
<blockquote style="color: blue; ">Vitamin C deficiency: ↓ cross-linking of tropocollagen→ ↓ tensile strength</blockquote></li><li>Trace metal deficiency</li><ul> <li>(1) Copper deficiency leads to decreased cross-linking in collagen (also in elastic tissue).</li><li>(2) Zinc deficiency leads to defects in removal of type III collagen in wound remodeling.</li><ul> <li>Type III collagen has decreased tensile strength, which impairs wound healing.</li> </ul> </ul> </ol><li>Glucocorticoids
<blockquote style="color: blue; ">Glucocorticoids: prevent scar formation</blockquote></li><ol type="a"> <li>Interfere with collagen formation and decrease tensile strength</li><li>Useful clinically in preventing excessive scar formation</li><ul> <li>Example-dexamethasone is used along with antibiotics to prevent scar formation in bacterial meningitis.
<blockquote style="color: blue; ">Keloids: excess type III collagen</blockquote></li> </ul> </ol> </ol>
</div><a name="PB002004"></a><div class="BB" style="color: rgb(47, 79, 79); ">Keloids, the raised scars caused by excessive synthesis of type III collagen, are common in blacks and may occur as the result of third-degree burns. Microscopically, keloids appear as irregular, thick collagen bundles that extend beyond the confines of the original injury (<span>[[Fig. 2-12|Figure 2-12]]</span>).</div></html>
<html><a name="HC002021"></a> <br><a name="P002029"></a><div class="PA" style="color: black; "><ol type="1"> <li>Liver</li><ol type="a"> <li>Mild injury (e.g., hepatitis A)</li><ul> <li>(1) Regeneration of hepatocytes</li><li>(2) Restoration to normal is possible if cytoarchitecture is intact.</li> </ul><li>Severe or persistent injury (e.g., hepatitis C)
<blockquote style="color: blue; ">Severe injury liver: regenerative nodules and fibrosis</blockquote></li><ul> <li>(1) Regenerative nodules develop that lack sinusoids and portal triads.</li><li>(2) Increased fibrosis occurs around regenerative nodules (see <span>[[Fig. 18-8|Figure 18-8]]</span>)</li><ul> <li>Potential for cirrhosis</li> </ul> </ul> </ol><li>Lung</li><ol type="a"> <li>Type II pneumocytes are the key repair cells of the lung.
<blockquote style="color: blue; ">Lung injury: type II pneumocyte is repair cell</blockquote></li><li>They replace damaged type I and type II pneumocytes.</li><li>They synthesize surfactant.</li> </ol><li>Brain</li><ol type="a"> <li>Astrocytes proliferate in response to an injury (e.g., brain infarction).
<blockquote style="color: blue; ">Brain injury: proliferation of astrocytes and microglial cells</blockquote></li><ul> <li>This is called gliosis.</li> </ul><li>Microglial cells (macrophages) are scavenger cells that remove debris (e.g., myelin).</li> </ol><li>Peripheral nerve transection</li><ol type="a"> <li>Distal degeneration of the axon (called wallerian degeneration) and myelin sheath</li><li>Proximal axonal degeneration up to the next node of Ranvier</li><li>Macrophages and Schwann cells phagocytose axonal/myelin debris.</li><li>Muscle undergoes atrophy in ∼15 days.</li><li>Nerve cell body undergoes central chromatolysis.</li><ul> <li>(1) Nerve cell body swells.</li><li>(2) Nissl bodies (composed of rough endoplasmic reticulum and free ribosomes) disappear centrally.</li><li>(3) Nucleus is peripheralized.</li> </ul><li>Schwann cells proliferate in the distal stump.
<blockquote style="color: blue; ">Peripheral nerve transection: Schwann cell key cell in reinnervation</blockquote></li><li>Axonal sprouts develop in the proximal stump and extend distally using Schwann cells for guidance.</li><li>Regenerated axon grows 2 to 3 mm/day.</li><li>Axon becomes remyelinated.</li><li>Muscle is eventually reinnervated.</li> </ol><li>Heart</li><ol type="a"> <li>Cardiac muscle is permanent tissue.</li><li>Damaged muscle is replaced by noncontractile scar tissue.</li> </ol> </ol>
</div><a name="B002001"></a><div class="BT">BOX 2-1 SEQUENCE OF FORMATION OF A TUBERCULOUS GRANULOMA</div><a name="PB002005"></a><div class="BB" style="color: rgb(47, 79, 79); "><ul> <li>The tubercle bacillus <i>Mycobacterium tuberculosis</i> undergoes phagocytosis by alveolar macrophages (processing of bacterial antigen).</li><li>Macrophages present antigen to CD4 T cells in association with class II antigen sites.</li><li>Macrophages release interleukin (IL) 12 (stimulates naïve T<sub>H</sub> cells to produce T<sub>H</sub>1 class memory cells) and IL-1 (causes fever; activates T<sub>H</sub>1 cells).</li><li>T<sub>H</sub>1 cells release IL-2 (stimulates T<sub>H</sub>1 proliferation), γ-interferon (activates macrophages to kill tubercle bacillus; epithelioid cells), and migration inhibitory factor (causes macrophages to accumulate).</li><li>Lipids from killed tubercle bacillus lead to caseous necrosis.</li><li>Activated macrophages fuse and become multinucleated giant cells.</li> </ul></div><a name="B002002"></a><div class="BT">BOX 2-2 WOUND HEALING BY PRIMARY AND SECONDARY INTENTION</div><a name="PB002006"></a><div class="BB" style="color: rgb(47, 79, 79); "><ul> <b>Primary Intention</b><li>Day 1: Fibrin clot (hematoma) develops. Neutrophils infiltrate the wound margins. There is increased mitotic activity of basal cells of squamous epithelium in the apposing wound margins.</li><li>Day 2: Squamous cells from apposing basal cell layers migrate under the fibrin clot and seal off the wound after 48 hours. Macrophages emigrate into the wound.</li><li>Day 3: Granulation tissue begins to form. Initial deposition of type III collagen begins but does <i>not</i> bridge the incision site. Macrophages replace neutrophils.</li><li>Days 4-6: Granulation tissue formation peaks, and collagen bridges the incision site.</li><li>Week 2: Collagen compresses blood vessels in fibrous tissue, resulting in reduced blood flow. Tensile strength is ∼10%.</li><li>Month 1: Collagenase remodeling of the wound occurs (breaks peptide bonds), with replacement of type III collagen by type I collagen. Tensile strength increases, reaching ∼80% within 3 months. Scar tissue is devoid of adnexal structures (e.g., hair, sweat glands) and inflammatory cells.</li> </ul>
<ul> <b>Secondary Intention</b><li>Typically, these wounds heal differently from primary intention:</li><li>More intense inflammatory reaction than primary healing</li><li>Increased amount of granulation tissue formation than in primary healing</li><li>Wound contraction caused by increased numbers of myofibroblasts</li> </ul></div></html>
![[2.III.A.Factors involved in tissue repair]]
<<tiddler [[2.III.A.Factors involved in tissue repair]]>>
![[2.III.B.Parenchymal cell regeneration]]
<<tiddler [[2.III.B.Parenchymal cell regeneration]]>>
![[2.III.C.Repair by connective tissue (fibrosis)]]
<<tiddler [[2.III.C.Repair by connective tissue (fibrosis)]]>>
![[2.III.D.Factors that impair healing]]
<<tiddler [[2.III.D.Factors that impair healing]]>>
![[2.III.E.Repair in other tissues]]
<<tiddler [[2.III.E.Repair in other tissues]]>>
<html><a name="HC002023"></a> <br><a name="P002032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acute inflammation (e.g., bacterial infection)</li><ol type="a"> <li>Absolute neutrophilic leukocytosis (<span>[[Fig. 2-13|Figure 2-13]]</span>)</li><ul> <li>(1) Accelerated release of neutrophils from the bone marrow</li><li>(2) Mediated by IL-1 and TNF</li> </ul><li>Left shift</li><ul> <li>Defined as greater than 10% band (stab) neutrophils or the presence of earlier precursors (e.g., metamyelocytes)</li> </ul><li>Toxic granulation</li><ul> <li>Prominence of azurophilic granules (primary lysosomes) in neutrophils</li> </ul><li>Increase in serum IgM
<blockquote style="color: blue; ">IgM: predominant immunoglobulin in acute inflammation</blockquote></li><ul> <li>(1) Peaks in 7 to 10 days</li><li>(2) Isotype switching (μ heavy chain replaced by γ heavy chain) in plasma cells to produce IgG peaks in 12 to 14 days.</li> </ul> </ol><li>Chronic inflammation (e.g., tuberculosis, rheumatoid arthritis)</li><ol type="a"> <li>Absolute monocytosis
<blockquote style="color: blue; ">IgG: predominant immunoglobulin in chronic inflammation</blockquote></li><li>Increase in serum IgG</li> </ol><li><span>[[Table 2-4|Table 2-4. SUMMARY OF LEUKOCYTES]]</span> summarizes cells involved in inflammation (<span>[[Fig. 2-14A to D|Figure 2-14]]</span>).</li><li>Peripheral blood effects of corticosteroid therapy</li><ol type="a"> <li>Absolute neutrophilic leukocytosis</li><ul> <li>Inhibits activation of neutrophil adhesion molecules</li> </ul><li>Lymphopenia</li><ul> <li>(1) Sequesters B and T lymphocytes in lymph nodes</li><li>(2) Signal for apoptosis of lymphocytes
<blockquote style="color: blue; ">Corticosteroid effect in blood: ↑ neutrophils; ↓ lymphocytes and eosinophils</blockquote></li> </ul><li>Eosinopenia</li><ul> <li>Sequesters eosinophils in lymph nodes</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC002024"></a> <br><a name="P002033"></a><div class="PA" style="color: black; "><ul> <li>ESR is the rate (mm/hour) of settling of RBCs in a vertical tube.</li><ol type="1"> <li>ESR is increased in acute and chronic inflammation (e.g., rheumatoid arthritis).</li><li>Plasma factor or RBC factors that promote rouleaux formation increase the ESR (<span>[[Fig. 2-15|Figure 2-15]]</span>).</li><ol type="a"> <li>Increase in fibrinogen (acute-phase reactant) in plasma decreases negative charge in RBCs, promoting rouleaux formation.</li><li>Anemia promotes rouleaux formation.
<blockquote style="color: blue; ">↑ ESR: ↑ fibrinogen, anemia</blockquote></li><ul> <li>Abnormally shaped RBCs (e.g., sickle cells) do <i>not</i> produce rouleaux.</li> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC002025"></a> <br><a name="P002034"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acute-phase reactant</li><li>Clinical usefulness</li><ol type="a"> <li>Sensitive indicator of necrosis associated with acute inflammation
<blockquote style="color: blue; ">CRP: marker of necrosis and disease activity</blockquote></li><ul> <li>CRP is increased in inflammatory (disrupted) atherosclerotic plaques and bacterial infections.</li> </ul><li>Excellent monitor of disease activity (e.g., rheumatoid arthritis)</li> </ol> </ol>
</div></html>
<html><a name="HC002026"></a><span>[[Fig. 2-16|Figure 2-16]]</span> <br> <br><a name="PB002007"></a><div class="BB" style="color: rgb(47, 79, 79); ">Proteins in serum are separated into individual fractions by SPE. Charged proteins placed in a buffered electrolyte solution will migrate toward one or the other electrode when a current is run through the solution. Proteins with the most negative charges (e.g., albumin) migrate to the positive pole, or anode, and those with the most positive charges (e.g., γ-globulins) remain at the negatively charged pole, or cathode. Beginning at the anode, proteins separate into five major peaks on cellulose acetate-albumin, followed by α<sub>1</sub>-, α<sub>2</sub>-, β-, and γ-globulins. The γ-globulins in decreasing order of concentration are IgG, IgA, and IgM (IgD and IgE are in very low concentration).</div><a name=""></a><div class="PA" style="color: black; "><ol type="1"> <li>Acute inflammation (see <span>[[Fig. 2-16A|Figure 2-16]]</span>)</li><ol type="a"> <li>Slight decrease in serum albumin</li><ul> <li>(1) Catabolic effect of inflammation</li><li>(2) Amino acids are used by the liver to synthesize acute phase reactants.
<blockquote style="color: blue; ">SPE acute inflammation: ↓ albumin; no alteration in γ-globulin peak</blockquote></li> </ul><li>Normal γ-globulin peak</li><ul> <li>Serum IgM is increased in acute inflammation; however, it does <i>not</i> alter the configuration of the γ-globulin peak.</li> </ul> </ol><li>Chronic inflammation (see <span>[[Fig. 2-16B|Figure 2-16]]</span>)</li><ol type="a"> <li>Greater decrease in serum albumin than in acute inflammation</li><li>Increase in γ-globulins due to increase in IgG
<blockquote style="color: blue; ">Polyclonal gammopathy: sign of chronic inflammation</blockquote></li><ul> <li>Diffuse increase in the γ-globulin peak is due to many clones of benign plasma cells producing IgG (i.e., polyclonal gammopathy).</li> </ul> </ol> </ol>
</div></html>
![[2.IV.A.Leukocytes]]
<<tiddler [[2.IV.A.Leukocytes]]>>
![[2.IV.B.Erythrocyte sedimentation rate (ESR)]]
<<tiddler [[2.IV.B.Erythrocyte sedimentation rate (ESR)]]>>
![[2.IV.C.C-reactive protein (CRP)]]
<<tiddler [[2.IV.C.C-reactive protein (CRP)]]>>
![[2.IV.D.Serum protein electrophoresis (SPE) in inflammation (Fig. 2-16)]]
<<tiddler [[2.IV.D.Serum protein electrophoresis (SPE) in inflammation (Fig. 2-16)]]>>
<html><a name="HC020002"></a> <br><a name="P020001"></a><div class="PA" style="color: black; "><ul> <li>May be associated with Hirschsprung's disease
<blockquote style="color: blue; ">Congenital megaloureter: association with Hirschsprung's disease</blockquote></li> </ul>
</div></html>
<html><a name="HC020003"></a> <br><a name="P020002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Manifestation of chronic inflammation</li><li>Smooth cysts project from the mucosa into the lumen.</li><ul> <li>Similar findings may be present in the bladder.
<blockquote style="color: blue; ">Ureteritis cystica: risk factor bladder adenocarcinoma</blockquote></li> </ul><li>May undergo glandular metaplasia and predispose to adenocarcinoma</li> </ol>
</div></html>
<html><a name="HC020004"></a> <br><a name="P020003"></a><div class="PA" style="color: black; "><ul> <li>Ureters are the most common site for stones to cause obstruction.</li> </ul>
</div></html>
![[20.I.A.Congenital megaloureter]]
<<tiddler [[20.I.A.Congenital megaloureter]]>>
![[20.I.B.Ureteritis cystica]]
<<tiddler [[20.I.B.Ureteritis cystica]]>>
![[20.I.C.Ureteral stones]]
<<tiddler [[20.I.C.Ureteral stones]]>>
![[20.I.D.Retroperitoneal fibrosis]]
<<tiddler [[20.I.D.Retroperitoneal fibrosis]]>>
![[20.I.E.Ureteral cancers]]
<<tiddler [[20.I.E.Ureteral cancers]]>>
<html><a name="HC020005"></a> <br><a name="P020004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes</li><ol type="a"> <li>Majority are idiopathic.</li><li>Ergot derivatives used in the treatment of migraines</li><li>Association with other sclerosing conditions</li><ul> <li>(1) Primary sclerosing cholangitis</li><li>(2) Sclerosing mediastinitis, Reidel's fibrosing thyroiditis</li> </ul><li>Retroperitoneal malignant lymphoma</li> </ol><li>Complications</li><ol type="a"> <li>Hydronephrosis is the most common complication.
<blockquote style="color: blue; ">Hydronephrosis: most common complication of retroperitoneal fibrosis</blockquote></li><li>May cause right scrotal varicocele (see section V)</li><ul> <li>Blocks the drainage of the right spermatic vein into the vena cava</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC020006"></a> <br><a name="P020005"></a><div class="PA" style="color: black; "><ul> <li>Transitional cell carcinoma (TCC) is the most common cancer.</li> </ul>
<blockquote style="color: blue; ">TCC: most common cancer of ureter</blockquote>
</div></html>
<html><a name="HC020008"></a> <br><a name="P020006"></a><div class="PA" style="color: black; "><ol type="1"> <li>Exstrophy of the bladder (<span>[[Fig. 20-1|Figure 20-1]]</span>)</li><ol type="a"> <li>Developmental failure of the anterior abdominal wall and bladder</li><ul> <li>(1) Bladder mucosa is exposed to the body surface.</li><li>(2) Often associated with epispadias (see section IV)
<blockquote style="color: blue; ">Exstrophy: developmental failure anterior abdominal wall and bladder</blockquote></li> </ul><li>Complications</li><ul> <li>(1) Inflammation predisposes to glandular metaplasia.</li><li>(2) Predisposition for adenocarcinoma of the bladder
<blockquote style="color: blue; ">Exstrophy: risk factor for bladder adenocarcinoma</blockquote></li> </ul> </ol><li>Urachal cyst remnants</li><ol type="a"> <li>Drainage of urine from umbilicus in a newborn; midline urachal cyst</li><li>Predispose to adenocarcinoma of the bladder</li><ul> <li>Most common cause of bladder adenocarcinoma
<blockquote style="color: blue; ">Urachal cyst remnants: most common cause of bladder adenocarcinoma; drainage of urine from umbilicus</blockquote></li> </ul> </ol> </ol>
</div></html>
<html><a name="HC020009"></a> <br><a name="P020007"></a><div class="PA" style="color: black; "><ol type="1"> <li>Risk factors for lower urinary tract (LUT) infection</li><ol type="a"> <li>Female sex</li><ul> <li>(1) Short urethra
<blockquote style="color: blue; ">Indwelling catheters: most common cause sepsis/urinary tract infections in a hospital</blockquote></li><li>(2) Ascending infection (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)</li> </ul><li>Indwelling urinary catheter</li><ul> <li>(1) Most common cause of sepsis in hospitalized patients</li><li>(2) Account for 50% of nosocomial urinary tract infections</li> </ul><li>Sexual intercourse</li><ul> <li>(1) "Honeymoon cystitis" from trauma to the urethra</li><li>(2) Voiding after intercourse reduces the risk for infection</li> </ul><li>Diabetes mellitus, neurogenic bladder
<blockquote style="color: blue; ">Cyclophosphamide: hemorrhagic cystitis; prevented with mesna</blockquote></li><li>Cyclophosphamide</li><ul> <li>(1) Produces hemorrhagic cystitis</li><li>(2) Prevented with mesna</li> </ul><li><i>Schistosoma hematobium</i></li><ul> <li>(1) Transmission</li><ul> <li>(a) Penetration of the skin by the fork-tailed cercariae</li><li>(b) Larvae enter veins in urinary bladder wall.</li><li>(c) Larvae develop into adult worms that deposit eggs.</li><li>(d) Host develops an intense inflammatory response.</li><li>(e) Produce squamous metaplasia of bladder epithelium
<blockquote style="color: blue; "><i>Schistosoma hematobium</i>: egg with large terminal spine</blockquote></li> </ul><li>(2) Eggs have a large terminal spine.</li><li>(3) Treatment is praziquantel.</li> </ul> </ol><li>Causes of acute cystitis</li><ol type="a"> <li><i>Escherichia coli</i>
<blockquote style="color: blue; "><i>E. coli:</i> most common uropathogen; sepsis in hospital</blockquote></li><ul> <li>(1) Most common uropathogen (80-90%)</li><li>(2) Gram-negative rod (<span>[[Fig. 20-2|Figure 20-2]]</span>)</li><li>(3) Most common cause of sepsis in a hospitalized patient</li><li>(4) Treatment is trimethoprim-sulfamethoxazole</li> </ul><li>Adenovirus</li><ul> <li>Causes hemorrhagic cystitis</li> </ul><li><i>Staphylococcus saprophyticus</i>
<blockquote style="color: blue; "><i>S. saprophyticus</i>: LUT in young, sexually active female; coagulase negative</blockquote></li><ul> <li>(1) Causes acute cystitis in young sexually active women</li><ul> <li>Accounts for ∼10% to 20% of LUT infections</li> </ul><li>(2) Coagulase negative</li><li>(3) Treatment is trimethoprim-sulfamethoxazole</li> </ul><li>Acute urethral syndrome in women</li><ul> <li>Female counterpart to nonspecific urethritis (NSU) in men</li> </ul><li><i>Chlamydia trachomatis</i>
<blockquote style="color: blue; "><i>C. trachomatis:</i> most common cause of acute urethral syndrome in women and NSU in men</blockquote></li><ul> <li>(1) Most common cause of acute urethral syndrome</li><li>(2) Identification of <i>Chlamydia</i></li><ul> <li>Polymerase chain reaction (PCR) testing of voided urine</li> </ul><li>(3) Treatment is azithromycin 1 g orally</li> </ul><li>Other pathogens</li><ul> <li><i>Mycoplasma hominis, Ureaplasma urealyticum, Neisseria gonorrhoeae</i>
<blockquote style="color: blue; ">LUT signs: dysuria, ↑ frequency, urgency</blockquote></li> </ul> </ol><li>Clinical findings in LUT infections</li><ol type="a"> <li>Dysuria (painful urination)</li><li>Increased frequency, urgency, nocturia</li><li>Suprapubic discomfort</li><li>Gross hematuria</li> </ol><li>Laboratory findings in LUT infections</li><ol type="a"> <li>Pyuria at or above 10 WBCs per high-power field (HPF) in a centrifuged specimen</li><ul> <li>More than 2 WBCs/HPF in an uncentrifuged specimen</li> </ul><li>Bacteriuria, hematuria</li><li>Positive dipstick for leukocyte esterase and nitrite (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)</li><li>At or above 10<sup>5</sup> colony-forming units (CFUs)/mL
<blockquote style="color: blue; ">≥10<sup>5</sup> CFUs/mL: gold standard for LUT infection</blockquote></li><ul> <li>Gold standard criterion of infection</li> </ul> </ol><li>Asymptomatic bacteriuria in women</li><ol type="a"> <li>Two successive cultures with 10<sup>5</sup> or more CFUs/mL in an asymptomatic patient</li><li>Causes</li><ul> <li>(1) Pregnancy</li><ul> <li>Acute pyelonephritis may occur in 1% to 2% of cases.
<blockquote style="color: blue; ">Asymptomatic bacteriuria: treat pregnant woman with amoxicillin; no treatment for healthy elderly women</blockquote></li> </ul><li>(2) Elderly women in nursing homes</li> </ul><li>Treatment</li><ul> <li>(1) Pregnant women</li><ul> <li>Amoxicillin</li> </ul><li>(2) Asymptomatic, healthy elderly women</li><ul> <li>No treatment necessary</li> </ul> </ul> </ol><li>Sterile pyuria
<blockquote style="color: blue; ">Sterile pyuria: neutrophils in the urine, negative standard culture</blockquote></li><ol type="a"> <li>Neutrophils in the urine and negative standard culture after 24 hours</li><ul> <li>Positive leukocyte esterase, negative nitrite</li> </ul><li>Causes</li><ul> <li>(1) <i>Chlamydia trachomatis</i></li><li>(2) Renal tuberculosis</li><li>(3) Acute tubulointerstitial nephritis (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)</li> </ul> </ol><li>Malacoplakia</li><ol type="a"> <li>Associated with a chronic <i>E. coli</i> infection of the bladder</li><li>Microscopic findings</li><ul> <li>(1) Yellow, raised mucosal plaques</li><li>(2) Foamy macrophages filled with laminated mineralized concretions
<blockquote style="color: blue; ">Malacoplakia: Michaelis-Gutmann bodies</blockquote></li><ul> <li>(a) Called Michaelis-Gutmann bodies</li><li>(b) Defective phagosomes that cannot degrade bacterial products</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC020010"></a> <br><a name="PB020001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Urinary bladder control and incontinence disorders</b>: Relaxation of the detrusor muscle is involved in the storage of urine, while contraction of the muscle is important in emptying the bladder. The sympathetic nervous system relaxes the detrusor muscle and contracts the internal sphincter; hence, it is important in the retention of urine in the bladder. In contradistinction, the parasympathetic nervous system is involved in emptying the bladder. It accomplishes this function by contracting the detrusor muscle and relaxing the internal sphincter muscle. There are four types of urinary incontinence: urge incontinence (40-70% of cases), overflow incontinence, stress incontinence, and functional incontinence. Urge incontinence is caused by overactivity of the detrusor muscle resulting in the production of low volumes of urine. Symptoms include increased urinary frequency, urgency, small volume voids, and nocturia. The most common causes are bladder irritation due to BPH, atrophic urethritis, and infection. Treatment is with anticholinergics, which inhibit parasympathetic stimulation of detrusor contraction. The mechanisms for outflow incontinence are outflow obstruction (e.g., BPH) or detrusor underactivity related to autonomic neuropathy (e.g., diabetes mellitus). Symptoms include dribbling and low urine flow. Treatment involves the use of cholinergic drugs to enhance muscle tone (i.e., increase detrusor contraction) or, if obstruction is the cause (e.g., BPH), α-adrenergic blockers to relax smooth muscles in the bladder neck. The mechanism for stress incontinence is laxity of pelvic floor muscles with a concomitant lack of bladder support. This may be the result of not maintaining the posterior urethrovesical angle of 90-100 degrees or a lack of estrogen; hence, this type of incontinence primarily occurs in women. Symptoms relate to the loss of urine when there is an increase in intra-abdominal pressure (e.g., laughing, cough, sneezing). Treatment is to increase internal sphincter tone with α-adrenergic agonists (contract smooth muscle cells at the bladder neck); using topical estrogen therapy; and encouraging the patient to do Kegel pelvic floor muscle exercises. If these treatments do not control the incontinence, then surgery is the final option. The mechanism for functional incontinence is inability to reach toilet facilities in time. Patients are normally continent; however, if they are taking diuretics or drinking too many caffeinated beverages incontinence may occur.
<blockquote style="color: blue; ">Retain urine: ↑ sympathetic activity-relax detrusor muscle, contract internal sphincter muscle</blockquote>
<blockquote style="color: blue; ">Void urine: ↑ parasympathetic activity-contract detrusor muscle, relax internal sphincter muscle</blockquote></div><a name="P020008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acquired diverticula
<blockquote style="color: blue; ">Acquired bladder diverticula: most common cause is BPH; chronic <i>E. coli</i> infection</blockquote></li><ol type="a"> <li>Most are due to benign prostatic hyperplasia (BPH)</li><li>Causes obstruction of urine outflow and increased intravesical pressure</li><li>Diverticulitis and stone formation are common complications</li> </ol><li>Cystocele</li><ol type="a"> <li>Common in middle-aged to elderly women</li><li>Mechanism</li><ul> <li>(1) Relaxation of pelvic support causes descent of the uterus
<blockquote style="color: blue; ">Cystocele: bladder wall protrudes into vagina</blockquote></li><li>(2) Bladder wall protrudes into the vagina</li><ul> <li>Creates a pouch that collects residual urine</li> </ul> </ul> </ol><li>Cystitis cystica and glandularis
<blockquote style="color: blue; ">Cystitis cystica/glandularis: risk of bladder adenocarcinoma</blockquote></li><ol type="a"> <li>Bladder rendition of ureteritis cystica</li><li>Increased risk for developing bladder adenocarcinoma</li> </ol> </ol>
</div></html>
<html><a name="HC020011"></a> <br><a name="P020009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Bladder papilloma</li><ul> <li>Very uncommon benign tumor</li> </ul><li>Transitional cell carcinoma (TCC)</li><ol type="a"> <li>Epidemiology
<blockquote style="color: blue; ">TCC: most common bladder cancer</blockquote></li><ul> <li>(1) Most common bladder cancer (>95% of cases)</li><li>(2) More common in men than women</li><li>(3) Incidence increases with age.</li><li>(4) Causes</li><ul> <li>(a) Smoking cigarettes (most common cause)</li><ul> <li>Less risk for other tobacco products
<blockquote style="color: blue; ">TCC: most common cause is smoking cigarettes</blockquote></li> </ul><li>(b) Workers in dye, rubber, or leather industries</li><li>(c) Cyclophosphamide</li><li>(d) Arsenic exposure</li><li>(e) Beer consumption</li><ul> <li>Due to nitrosamines in beer</li> </ul><li>(f) <i>Schistosoma hematobium</i>
<blockquote style="color: blue; ">Squamous cell carcinoma of bladder: <i>S. hematobium</i> infection</blockquote></li><ul> <li>70% produce squamous cell carcinoma, 30% TCC</li> </ul> </ul> </ul><li>Pathogenesis</li><ul> <li>(1) Genetic factors</li><ul> <li>(a) Numerous chromosomes implicated</li><li>(b) Genes implicated: <i>TP53</i> and <i>RB</i> suppressor genes; <i>HRAS</i> protooncogene</li><li>(c) Alteration in epidermal derived growth factor receptor</li> </ul><li>(2) Environmental factors (see earlier discussion)
<blockquote style="color: blue; ">TCC: multifocal tumor; recurrences are the rule</blockquote></li><li>(3) Multifocality ("field effect") and recurrence are the rule.</li><ul> <li>(a) Common malignant stem cell abnormality</li><li>(b) Reimplantation of the tumor from another site</li> </ul> </ul><li>Gross and microscopic findings</li><ul> <li>(1) Low-grade cancers</li><ul> <li>Usually papillary and are <i>not</i> usually invasive (<span>[[Fig. 20-3|Figure 20-3]]</span>)</li> </ul><li>(2) High-grade cancers</li><ul> <li>Papillary or flat and are usually invasive</li> </ul><li>(3) Most common sites</li><ul> <li>Lateral or posterior walls at the base of the bladder</li> </ul><li>(4) Significance of blood group antigens (A, B, or H)</li><ul> <li>Better prognosis if the tumor has the antigens</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Painless gross/microscopic hematuria
<blockquote style="color: blue; ">TCC: painless hematuria most common sign</blockquote></li><ul> <li>Most common sign (70-90%)</li> </ul><li>(2) Dysuria, increased frequency of urination</li> </ul><li>Treatment</li><ul> <li>(1) Surgical resection</li><li>(2) Intravesical chemotherapy</li><li>(3) Radiotherapy</li> </ul><li>Prognosis</li><ul> <li>Five-year survival rate for all stages combined is 80%.</li> </ul> </ol><li>Squamous cell carcinoma of the bladder</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Association with <i>Schistosoma hematobium</i></li><ul> <li>Eggs are located in the urinary bladder venous plexus.
<blockquote style="color: blue; ">Bladder squamous cancer: <i>S. hematobium</i></blockquote></li> </ul><li>(2) Common cancer in Egypt</li><li>(3) 70% of cancers are squamous cell carcinoma, 30% are TCC</li> </ul><li>Pathogenesis of squamous cell carcinoma</li><ul> <li>(1) Eggs are surrounded by eosinophils.</li><li>(2) IgE antibodies are attached to the eggs.</li><li>(3) Eosinophils have Fc receptors for IgE.
<blockquote style="color: blue; ">Killing helminth eggs: type II hypersensitivity reaction involving eosinophils</blockquote></li><li>(4) Eosinophils attach to receptors and release major basic protein, which destroys the egg.</li><ul> <li>Type II hypersensitivity reaction</li> </ul><li>(5) Chronic bladder irritation/infection produces squamous metaplasia.</li><ul> <li>Metaplasia can progress to dysplasia and squamous cell carcinoma.</li> </ul> </ul> </ol><li>Causes of adenocarcinoma of the bladder</li><ol type="a"> <li>Urachal remnants (most common cause)</li><li>Cystitis glandularis</li><li>Exstrophy of the bladder</li> </ol><li>Embryonal rhabdomyosarcoma (sarcoma botryoides)</li><ol type="a"> <li>Most common sarcoma in children</li><ul> <li>Accounts for ∼3% of childhood cancer</li> </ul><li>Most common site for boys is urinary system.
<blockquote style="color: blue; ">Embryonal sarcoma: most common sarcoma in children; in boys, protrudes from urethra</blockquote></li><ul> <li>Presents as grape-like masses protruding from the urethral orifice</li> </ul><li>Most common site in girls is the vagina.</li> </ol><li>Cancers invading the bladder
<blockquote style="color: blue; ">Cancers invading bladder: cervical and prostate cancer</blockquote></li><ol type="a"> <li>Invasive cervical cancer and prostate cancer</li><li>Produce obstruction of the urethra and the ureters</li><li>Produce hydronephrosis, postrenal azotemia, and death by renal failure</li> </ol> </ol>
</div></html>
![[20.II.A.Congenital disorders]]
<<tiddler [[20.II.A.Congenital disorders]]>>
![[20.II.B.Acute and chronic cystitis]]
<<tiddler [[20.II.B.Acute and chronic cystitis]]>>
![[20.II.C.Miscellaneous disorders]]
<<tiddler [[20.II.C.Miscellaneous disorders]]>>
![[20.II.D.Bladder tumors]]
<<tiddler [[20.II.D.Bladder tumors]]>>
<html><a name="HC020013"></a> <br><a name="P020013"></a><div class="PA" style="color: black; "><ol type="1"> <li>Chlamydial and gonococcal infections in men and women</li><ul> <li>Urethra is the most common site for these sexually transmitted diseases.
<blockquote style="color: blue; ">STD urethritis: <i>Chlamydia</i> and <i>Neisseria gonorrhoeae</i></blockquote></li> </ul><li>Nonvenereal diseases causing urethritis</li><ol type="a"> <li>Most commonly due to <i>E. coli</i></li><li>Complications</li><ul> <li>(1) Cystitis in women</li><li>(2) Prostatitis in men</li> </ul> </ol><li><i>Chlamydial</i> urethritis is a common component of Reiter's syndrome in men.
<blockquote style="color: blue; ">Reiter's syndrome: <i>Chlamydial</i> urethritis, conjunctivitis, HLA-B27 arthritis</blockquote></li><ol type="a"> <li>Urethritis</li><li>Sterile conjunctivitis</li><li>HLA-B27-associated arthritis (refer to <span macro="tag [[23 Musculoskeletal and Soft Tissue Disorders]] [[Chapter 23]]"></span>)</li> </ol> </ol>
</div></html>
<html><a name="HC020014"></a> <br><a name="P020014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Female dominant disease</li><li>Friable, red painful mass is present at the urethral orifice.</li><li>Chronically inflamed granulation tissue causes bleeding.</li> </ol>
</div></html>
<html><a name="HC020015"></a> <br><a name="P020015"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Urethra: squamous cell carcinoma most common cause</blockquote>
<ul> <li>Most common cancer of the urethra</li> </ul>
</div></html>
![[20.III.A.Infections]]
<<tiddler [[20.III.A.Infections]]>>
![[20.III.B.Urethral caruncle]]
<<tiddler [[20.III.B.Urethral caruncle]]>>
![[20.III.C.Squamous cell carcinoma]]
<<tiddler [[20.III.C.Squamous cell carcinoma]]>>
<html><a name="HC020017"></a> <br><a name="P020016"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hypospadias
<blockquote style="color: blue; ">Hypospadias: abnormal opening on ventral surface of penis</blockquote></li><ol type="a"> <li>Abnormal opening on the ventral surface of the penis (<span>[[Fig. 20-4|Figure 20-4]]</span>)</li><li>Most common malformation of urethral groove</li><li>Risk factors
<blockquote style="color: blue; ">Hypospadias: most common malformation of urethral grove</blockquote></li><ul> <li>(1) Father or previous male sibling had defect</li><li>(2) Monozygotic twins</li><ul> <li>? Insufficient production of human chorionic gonadotropin by single placenta</li> </ul> </ul><li>Frequently associated with ventral curvature of penis</li><ul> <li>Called chordee</li> </ul><li>Pathogenesis
<blockquote style="color: blue; ">Hypospadias: faulty closure urethral folds; androgen dysfunction</blockquote></li><ul> <li>(1) Due to faulty closure of the urethral folds</li><li>(2) Possibly related to abnormal androgen production</li> </ul> </ol><li>Epispadias
<blockquote style="color: blue; ">Epispadias: abnormal opening on dorsal surface of penis; defect of genital tubercle</blockquote></li><ol type="a"> <li>Abnormal opening on the dorsal surface of the penis</li><li>Due to a defect in the genital tubercle</li> </ol> </ol>
</div></html>
<html><a name="HC020018"></a> <br><a name="P020017"></a><div class="PA" style="color: black; "><ol type="1"> <li>Orifice of the prepuce is too small to retract over the head of the penis
<blockquote style="color: blue; ">Phimosis: orifice of prepuce cannot retract over head of penis</blockquote></li><li>Commonly associated with infections</li> </ol>
</div></html>
<html><a name="HC020019"></a> <br><a name="P020018"></a><div class="PA" style="color: black; "><ol type="1"> <li>Infection of the glans and prepuce</li><ol type="a"> <li>Usually occurs in uncircumcised males with poor hygiene
<blockquote style="color: blue; ">Balanoposthitis: infection of glans and prepuce</blockquote></li><li>Accumulation of smegma leads to infection.</li><ul> <li><i>Candida</i>, pyogenic bacteria, and anaerobes</li> </ul> </ol><li>Inflammatory scarring may produce an acquired phimosis.</li> </ol>
</div></html>
<html><a name="HC020020"></a> <br><a name="P020019"></a><div class="PA" style="color: black; "><ol type="1"> <li>Peyronie's disease</li><ol type="a"> <li>Type of fibromatosis (refer to <span macro="tag [[23 Musculoskeletal and Soft Tissue Disorders]] [[Chapter 23]]"></span>)</li><li>Painful contractures of the penis
<blockquote style="color: blue; ">Peyronie's disease: fibromatosis; lateral curvature of penis; infertility</blockquote></li><ul> <li>Causes lateral curvature of the penis</li> </ul><li>May cause infertility</li> </ol><li>Priapism</li><ol type="a"> <li>Persistent and painful erection
<blockquote style="color: blue; ">Priapism: persistent painful erection</blockquote></li><li>Causes include sickle cell disease, penile trauma</li> </ol> </ol>
</div></html>
<html><a name="HC020021"></a> <br><a name="P020020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Bowen's disease</li><ol type="a"> <li>Leukoplakia involving the shaft of the penis and scrotum</li><ul> <li>(1) Patients usually >35 years old</li><li>(2) Association with human papillomavirus (HPV) type 16</li> </ul><li>Precursor for invasive squamous cell carcinoma (∼10% of cases)</li><li>Association with other types of visceral cancer
<blockquote style="color: blue; ">Risk factors for invasive squamous cell carcinoma: Bowen's disease, erythroplasia of Queyrat</blockquote></li> </ol><li>Erythroplasia of Queyrat</li><ol type="a"> <li>Erythroplakia located on the mucosal surface of the glans and prepuce</li><li>HPV type 16 association</li><li>Precursor for invasive squamous cell carcinoma</li> </ol><li>Bowenoid papulosis
<blockquote style="color: blue; ">Bowenoid papulosis: HPV 16; no invasive cancer</blockquote></li><ol type="1"> <li>Multiple pigmented reddish brown papules on the external genitalia</li><li>Association with HPV type 16</li><li>Does <i>not</i> develop into invasive squamous cell carcinoma</li><ul> <li>Only CIS with no predisposition for invasion</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC020022"></a> <br><a name="P020021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common cancer of the penis
<blockquote style="color: blue; ">Penis cancer: squamous cell carcinoma</blockquote></li><ol type="a"> <li>Usually affects men 40 to 70 years old</li><li>Most common sites</li><ul> <li>Glans or mucosal surface of prepuce</li> </ul> </ol><li>HPV type 16, 18 association in two thirds of cases</li><ul> <li>Smoking may act as a cocarcinogen with HPV.</li> </ul><li>Risk factors</li><ol type="a"> <li>Lack of circumcision
<blockquote style="color: blue; ">Circumcision: protects against developing cancer of the penis; HPV 16, 18 relationship</blockquote></li><ul> <li>Greatest risk factor</li> </ul><li>Bowen's disease, erythroplasia of Queyrat</li> </ol><li>Metastasizes to inguinal and iliac nodes</li> </ol>
</div></html>
![[20.IV.A.Malformations of the urethral groove]]
<<tiddler [[20.IV.A.Malformations of the urethral groove]]>>
![[20.IV.B.Phimosis]]
<<tiddler [[20.IV.B.Phimosis]]>>
![[20.IV.C.Balanoposthitis]]
<<tiddler [[20.IV.C.Balanoposthitis]]>>
![[20.IV.D.Miscellaneous disorders]]
<<tiddler [[20.IV.D.Miscellaneous disorders]]>>
![[20.IV.E.Carcinoma in situ (CIS)]]
<<tiddler [[20.IV.E.Carcinoma in situ (CIS)]]>>
![[20.IV.F.Squamous cell carcinoma]]
<<tiddler [[20.IV.F.Squamous cell carcinoma]]>>
<html><a name="HC020049"></a> <br><a name="P020048"></a><div class="PA" style="color: black; "><ol type="1"> <li>Psychogenic</li><ol type="a"> <li>Most common cause of impotence in young men
<blockquote style="color: blue; ">Impotence + preserved NPT: psychogenic cause of impotence</blockquote></li><li>Stress at work, marital conflicts, performance anxiety</li><li>Nocturnal penile tumescence (NPT)</li><ul> <li>(1) Average male has ∼5 erections while sleeping at night.</li><li>(2) NPT is preserved in impotence that is due to psychogenic causes.</li><li>(3) All other causes of impotence have a loss of NPT.</li> </ul> </ol><li>Decreased testosterone</li><ul> <li>Decreased libido (see section VII, Male Hypogonadism)</li> </ul><li>Vascular insufficiency
<blockquote style="color: blue; ">Vascular insufficiency: most common cause impotence men > 50 years old</blockquote></li><ol type="a"> <li>Most common cause of impotence in men > 50 years old</li><li>Example-Leriche syndrome</li><ul> <li>(1) Impotence due to vascular insufficiency</li><li>(2) Aortoiliac atherosclerosis with decreased penal blood flow</li><li>(3) Calf claudication with atrophy</li><li>(4) Diminished femoral pulse</li> </ul> </ol><li>Neurologic disease</li><ol type="a"> <li>Parasympathetic system (S2-S4) is necessary for erection.
<blockquote style="color: blue; ">Parasympathetic for erection: S2-S4</blockquote></li><li>Sympathetic system (T12-L1) is necessary for ejaculation.
<blockquote style="color: blue; ">Sympathetic for ejaculation: T12-L1</blockquote></li><li>Neurogenic causes of impotence</li><ul> <li>(1) Multiple sclerosis</li><li>(2) Autonomic neuropathy due to diabetes mellitus
<blockquote style="color: blue; ">Neurologic causes erectile dysfunction: multiple sclerosis, diabetes mellitus</blockquote></li><li>(3) Radical prostatectomy</li> </ul> </ol><li>Drug effects; examples:</li><ol type="a"> <li>Leuprolide (GnRH agonist)</li><li>Methyldopa, psychotropics</li> </ol><li>Endocrine disease</li><ol type="a"> <li>Diabetes mellitus</li><ul> <li>Autonomic neuropathy + vascular insufficiency
<blockquote style="color: blue; ">Drugs erectile dysfunction: leuprolide, methyldopa, psychotropics</blockquote></li> </ul><li>Primary hypothyroidism</li><ul> <li>Increased prolactin inhibits GnRH release
<blockquote style="color: blue; ">Endocrine disease erectile dysfunction: diabetes, primary hypothyroidism, prolactinoma</blockquote></li> </ul><li>Prolactinoma</li><ul> <li>Prolactin inhibits GnRH release</li> </ul> </ol><li>Penis disorders</li><ol type="a"> <li>Peyronie's disease (fibromatosis)</li><li>Priapism</li> </ol> </ol>
</div></html>
<html><a name="HC020050"></a> <br><a name="P020049"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sildenafil (Viagra)</li><ol type="a"> <li>Most common drug used for the treatment of erectile dysfunction</li><li>Mechanism</li><ul> <li>(1) Inhibits the breakdown of cyclic guanosine monophosphate (cGMP) by type 5 phosphodiesterase
<blockquote style="color: blue; ">Sildenafil: increases cGMP, which causes vasodilation in corpus cavernosum</blockquote></li><li>(2) Increased levels of cGMP cause vasodilation in the corpus cavernosum and the penis.</li> </ul> </ol><li>Yohimbe</li><ul> <li>Herb that produces vasodilatation of vessels
<blockquote style="color: blue; ">Yohimbe: vasodilation</blockquote></li> </ul> </ol>
</div></html>
![[20.IX.A.Causes of erectile dysfunction]]
<<tiddler [[20.IX.A.Causes of erectile dysfunction]]>>
![[20.IX.B.Drugs used in erectile dysfunction]]
<<tiddler [[20.IX.B.Drugs used in erectile dysfunction]]>>
<html><a name="HC020024"></a> <br><a name="P020023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Normal descent of testes</li><ol type="a"> <li>Transabdominal phase
<blockquote style="color: blue; ">Testes transabdominal phase: müllerian inhibitory factor</blockquote></li><ul> <li>(1) Testes descend to lower abdomen or pelvic brim</li><li>(2) Müllerian inhibitory factor (anti-müllerian hormone) is responsible for this phase</li> </ul><li>Inguinoscrotal phase</li><ul> <li>(1) Descent through the inguinal canal into the scrotum</li><li>(2) Androgen- and human chorionic gonadotropin (hCG)-dependent
<blockquote style="color: blue; ">Testis inguinoscrotal phase: androgen- and hCG-dependent</blockquote></li> </ul> </ol><li>Cryptorchidism</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Incomplete or improper descent of the testis into the scrotal sac
<blockquote style="color: blue; ">Cryptorchid testis: incomplete or improper descent of testis into scrotal sac</blockquote></li><li>(2) Most common genitourinary disorder in male children</li><li>(3) Occurs 30% premature and 5% of full-term males</li><li>(4) Associations
<blockquote style="color: blue; ">Cryptorchid testis: most common GU disorder in male children</blockquote></li><ul> <li>Testicular feminization, Kallmann's syndrome, cystic fibrosis</li> </ul><li>(5) Locations</li><ul> <li>(a) Inguinal canal most common site (80%)</li><ul> <li>Palpable mass; majority are unilateral (90%)</li> </ul><li>(b) Intra-abdominal (5-10% of cases)</li> </ul><li>(6) Many will spontaneously descend by 3 months of age</li><ul> <li>(a) Due to combination of androgens and hCG</li><li>(b) Spontaneous descent uncommon after 3 months</li> </ul> </ul><li>Complications if uncorrected</li><ul> <li>(1) Potential for infertility</li><ul> <li>(a) Arrest in germ cell maturation</li><li>(b) Testicular atrophy</li><li>(c) Similar changes occur in the normally descended contralateral testis.</li><li>(d) Greatest risk if intra-abdominal or long duration in inguinal canal</li> </ul><li>(2) Increased risk for developing a seminoma
<blockquote style="color: blue; ">Cryptorchid testis: risk for seminoma and infertility of cryptorchid testis + normally descended testis</blockquote></li><ul> <li>(a) Five- to tenfold increased risk for cancer in cryptorchid testis</li><li>(b) Risk also applies to the normally descended testicle</li> </ul><li>(3) Increased risk for undescended testis to undergo torsion</li> </ul><li>Treatment</li><ul> <li>(1) Orchiopexy as early as 6 months; should be completed by 2 years of age</li><li>(2) Hormonal therapy with hCG produces variable results</li><li>(3) Administration gonadotropin-releasing hormone (GnRH) prior to orchiopexy may improve fertility in adult.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC020025"></a> <br><a name="P020024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Mumps</li><ol type="a"> <li>Infertility is uncommon.</li><li>Most cases are unilateral.</li><li>Orchitis is more likely in an older child or adult.
<blockquote style="color: blue; ">Orchitis: mumps, syphilis, HIV</blockquote></li> </ol><li>Congenital or acquired syphilis</li><li>HIV</li><li>Extension of acute epididymitis</li> </ol>
</div></html>
<html><a name="HC020026"></a> <br><a name="P020025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes</li><ol type="a"> <li>Pathogens in patients < 35 years old</li><ul> <li>(1) <i>Neisseria gonorrhoeae</i></li><li>(2) <i>Chlamydia trachomatis</i></li> </ul><li>Pathogens in patients > 35 years old</li><ul> <li>(1) <i>E. coli</i></li><li>(2) <i>Pseudomonas aeruginosa</i>
<blockquote style="color: blue; ">Epididymitis: <35 years old, consider STD; >35 years old, <i>E. coli, P. aeruginosa</i></blockquote></li> </ul><li>Tuberculosis</li><ul> <li>(1) Begins in the epididymis</li><ul> <li>Spreads to the seminal vesicles, prostate, and testicles</li> </ul><li>(2) Caseating granulomatous inflammation</li> </ul><li>AIDS</li><ul> <li>Association with cytomegalovirus, <i>Toxoplasma</i>, <i>Salmonella</i></li> </ul> </ol><li>Signs and symptoms of acute epididymitis
<blockquote style="color: blue; ">Epididymitis: scrotal pain with radiation into spermatic cord</blockquote></li><ol type="a"> <li>Usually unilateral scrotal pain with radiation into spermatic cord or flank</li><li>Scrotal swelling, epididymal tenderness</li><li>Urethral discharge</li><ul> <li>If it is sexually transmitted</li> </ul><li>Prehn's sign
<blockquote style="color: blue; ">Prehn's sign: elevation of scrotum ↓ pain</blockquote></li><ul> <li>Elevation of the scrotum decreases pain.</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>If <35 years old, ceftriaxone + doxycycline (STD treatment)</li><li>If >35 years old, ciprofloxacin extended release</li> </ol> </ol>
</div></html>
<html><a name="HC020027"></a> <br><a name="P020026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Occurs in 15% to 20% of all males</li><ul> <li>(1) Usually between 15 and 25 years of age</li><li>(2) Rarely occurs after 40 years old</li> </ul><li>Occurs in 40% of infertile males</li><li>Most common cause of left-sided scrotal enlargement in an adult</li><ul> <li>"Bag of worms" appearance (<span>[[Fig. 20-5|Figure 20-5]]</span>)</li> </ul><li>Left spermatic vein drains into the left renal vein</li><ul> <li>(1) Increased resistance to blood flow
<blockquote style="color: blue; ">Varicocele: most often left-sided; spermatic vein empties into left renal vein</blockquote></li><li>(2) Blockage of left renal vein can also produce a varicocele.</li><ul> <li>Examples-renal cell carcinoma invading renal vein; superior mesenteric artery compressing left renal vein
<blockquote style="color: blue; ">Varicocele: smoker with sudden onset of left varicocele; consider renal carcinoma invading renal vein</blockquote></li> </ul> </ul><li>Right spermatic vein drains into the vena cava</li><ul> <li>(1) Blockage of right spermatic vein produces right-sided varicocele.</li><li>(2) Examples-retroperitoneal fibrosis; thrombosis inferior vena cava</li> </ul> </ol><li>Pathogenesis</li><ul> <li>Incompetent valves in left spermatic vein from increased pressure</li> </ul><li>Clinical</li><ol type="a"> <li>Aching pain in scrotum</li><li>Dragging sensation in testicle</li><li>Visible "bag of worms"
<blockquote style="color: blue; ">Varicocele: "bag of worms" appearance</blockquote></li><li>Infertility (controversial)</li><ul> <li>Heat decreases spermatogenesis.</li> </ul> </ol><li>Diagnosis by ultrasound</li><li>Treatment</li><ol type="a"> <li>Varicocelectomy</li><li>Embolization by intervention radiologist</li> </ol> </ol>
</div></html>
<html><a name="HC020028"></a> <br><a name="P020027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Majority occur between 12 and 18 years old.</li><li>Predisposing factors</li><ul> <li>(1) Violent movement or physical trauma
<blockquote style="color: blue; ">Torsion of testicle: violent movement or trauma most common cause</blockquote></li><ul> <li>Most common causes</li> </ul><li>(2) Cryptorchid testis</li><li>(3) Atrophy of testis</li> </ul><li>Twisting of spermatic cord cuts off the venous/arterial blood supply</li><ul> <li>Danger for hemorrhagic infarction of the testicle</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Sudden onset of testicular pain</li><li>Absent cremasteric reflex (key diagnostic finding)
<blockquote style="color: blue; ">Torsion of testicle: absent cremasteric reflex, testis high in inguinal canal</blockquote></li><ul> <li>Stroking the inner thigh with a tongue blade normally causes the scrotum to retract.</li> </ul><li>Testicle is drawn up into the inguinal canal.</li> </ol><li>Diagnosis is by ultrasound.</li><li>Treatment</li><ol type="a"> <li>One third spontaneously remit.</li><li>Surgery is imperative within 12 hours for those that do not remit.</li> </ol> </ol>
</div></html>
<html><a name="HC020029"></a> <br><a name="P020028"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Hydrocele: most common cause of scrotal enlargement</blockquote>
<ol type="1"> <li>Most common cause of scrotal enlargement</li><ol type="a"> <li>Due to a failure of closure of the tunica vaginalis</li><li>Fluid accumulates in serous space between the layers of the tunica vaginalis.</li><li>Invariably associated with an indirect inguinal hernia
<blockquote style="color: blue; ">Hydrocele: persistent tunica vaginalis; inguinal hernia also present</blockquote></li> </ol><li>Diagnosis</li><ul> <li>Ultrasound distinguishes fluid versus a testicular mass causing scrotal enlargement.</li> </ul><li>Other fluid accumulations</li><ol type="a"> <li>Hematocele contains blood.</li><li>Spermatocele contains sperm.</li> </ol><li>Treatment is surgery.</li> </ol>
</div></html>
<html><a name="HC020030"></a> <br><a name="P020029"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common malignancy between ages 15 and 35</li><li>Occurs more often in whites than blacks</li> </ol><li>Types of testicular tumors</li><ol type="a"> <li>Malignant testicular tumors are most often germ cell in origin (95% of cases).</li><li>Benign testicular tumors are usually sex-cord stromal tumors (5% of cases).</li><li>Classification of germ cell tumors</li><ul> <li>(1) 40% are of one cell type
<blockquote style="color: blue; ">Seminoma: most common testicular cancer</blockquote></li><ul> <li>Seminoma is the most common type (40%).</li> </ul><li>(2) 60% are mixtures of two or more patterns.</li><ul> <li>Most common mixture is embryonal carcinoma, teratoma, choriocarcinoma, yolk sac tumor.
<blockquote style="color: blue; ">Testicular cancers: seminomas and nonseminomas</blockquote></li> </ul><li>(3) Best classified as seminomas or nonseminomatous</li> </ul> </ol><li>Risk factors</li><ol type="a"> <li>Cryptorchid testicle
<blockquote style="color: blue; ">Testicular cancer: cryptorchidism most common risk factor</blockquote></li><ul> <li>(1) Overall most common risk factor</li><li>(2) Greatest risk is an intra-abdominal cryptorchid testis.</li> </ul><li>Testicular feminization (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><li>Klinefelter's syndrome (XXY) (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><li>Inguinal hernia, mumps orchitis</li> </ol><li>Clinical finding</li><ul> <li>Unilateral, painless enlargement of the testis
<blockquote style="color: blue; ">Unilateral, painless testicular mass: testicular cancer</blockquote></li> </ul><li>Tumor markers</li><ol type="a"> <li>α-Fetoprotein (AFP)</li><ul> <li>Yolk sac (endodermal sinus) tumor origin</li> </ul><li>Human chorionic gonadotropin (hCG)</li><ul> <li>Choriocarcinoma
<blockquote style="color: blue; ">Testicular cancer markers: AFP, hCG</blockquote></li> </ul><li>Lactate dehydrogenase</li><ul> <li>(1) Nonspecific cancer enzyme</li><li>(2) Degree of elevation correlates with tumor mass</li> </ul> </ol><li>Summary of testicular tumors (<span>[[Table 20-1|Table 20-1. TESTICULAR TUMORS*]]</span> and <span>[[Figs. 20-6|Figure 20-6]]</span> and <span>[[20-7|Figure 20-7]]</span>)</li><li>Diagnosis</li><ol type="a"> <li>Ultrasound
<blockquote style="color: blue; ">Testicular cancer: para-aortic nodes <i>not</i> inguinal nodes</blockquote></li><li>CT scan or MRI of pelvis and abdomen</li><ul> <li>Testicular cancer most often involves para-aortic lymph nodes</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Inguinal orchiectomy</li><li>Adjuvant chemotherapy</li> </ol> </ol>
</div></html>
![[20.V.A.Cryptorchidism]]
<<tiddler [[20.V.A.Cryptorchidism]]>>
![[20.V.B.Orchitis]]
<<tiddler [[20.V.B.Orchitis]]>>
![[20.V.C.Epididymitis]]
<<tiddler [[20.V.C.Epididymitis]]>>
![[20.V.D.Varicocele]]
<<tiddler [[20.V.D.Varicocele]]>>
![[20.V.E.Torsion of the testicle]]
<<tiddler [[20.V.E.Torsion of the testicle]]>>
![[20.V.F.Hydrocele]]
<<tiddler [[20.V.F.Hydrocele]]>>
![[20.V.G.Testicular tumors]]
<<tiddler [[20.V.G.Testicular tumors]]>>
<html><a name="HC020032"></a> <br><a name="P020031"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">DHT: embryologic development of prostate</blockquote>
<ol type="1"> <li>Dihydrotestosterone (DHT) is responsible for developing the prostate.</li><li>Zones of the prostate</li><ol type="a"> <li>Peripheral zone</li><ul> <li>(1) Palpated during a digital rectal examination (DRE)</li><li>(2) Primary site for prostate cancer</li> </ul><li>Transitional zone</li><ul> <li>Primary site for the glandular component of BPH</li> </ul><li>Periurethral zone</li><ul> <li>Primary site for the fibromuscular (stromal) component of BPH</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC020033"></a> <br><a name="P020032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology
<blockquote style="color: blue; ">Prostatitis: chronic > acute</blockquote></li><ol type="a"> <li>Approximately 50% of males develop prostatitis in their lifetime.</li><li>Chronic prostatitis is more common than acute prostatitis.</li><li>Causes</li><ul> <li>(1) Acute prostatitis</li><ul> <li>(a) Intraprostate reflux of urine from the posterior urethra or urinary bladder</li><li>(b) Often associated with acute cystitis</li><li>(c) Young to middle aged adult males
<blockquote style="color: blue; ">Acute prostatitis < 35 years old: consider <i>Chlamydia</i>, <i>Neisseria</i></blockquote></li><li>(d) Pathogens in patients < 35 years old</li><ul> <li>Consider <i>Chlamydia trachomatis</i>, <i>Neisseria gonorrhoeae</i></li> </ul><li>(e) Pathogens in patients > 35 years old</li><ul> <li><i>E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae</i></li> </ul> </ul><li>(2) Chronic prostatitis
<blockquote style="color: blue; ">Chronic prostatitis: majority are abacterial</blockquote></li><ul> <li>(a) Majority are abacterial</li><li>(b) Common in bicycle riders</li><li>(c) Chronic bacterial infection</li><ul> <li>Due to recurrent acute prostatitis</li> </ul> </ul> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Dysuria, urgency, increased frequency</li><li>Fever occurs in acute prostatitis.
<blockquote style="color: blue; ">Chronic prostatitis: can radiate to lower back, perineum, suprapubic area</blockquote></li><li>Lower back, perineal, or suprapubic pain</li><li>Painful/swollen gland on rectal examination</li><li>Hematuria may occur.</li> </ol><li>Fractionated urine culture and examination for WBCs</li><ol type="a"> <li>Specimen collections</li><ul> <li>Some consider this cumbersome and impractical.</li> </ul><ul> <li>(1) First 10 mL is the urethral component.</li><li>(2) Second midstream sample is the bladder component.</li><li>(3) Third specimen at the end of micturition is the prostate component.</li><li>(4) Fourth specimen is secretions milked out after prostate massage.</li><ul> <li>Contraindicated in acute prostatitis</li> </ul> </ul><li>Diagnosis of prostatitis</li><ul> <li>(1) More than 20 WBCs/HPF in the third and fourth samples suggests acute prostatitis.</li><li>(2) Increased bacterial count in third and fourth specimens is confirmatory.</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>If acute prostatitis in men < 35 years old, ceftriaxone + doxycycline (STD treatment)</li><li>If acute prostatitis in men > 35 years old, ciprofloxacin extended release of trimethoprim-sulfamethoxazole</li><li>If chronic bacterial prostatitis, ciprofloxacin</li> </ol> </ol>
</div></html>
<html><a name="HC020034"></a> <br><a name="P020033"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">BPH: most common cause of enlarged prostate in men > 50 years old</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Age-dependent change</li><ul> <li>(1) Majority of men develop BPH as they age.</li><li>(2) Approximately 80% have BPH at 80 years of age.</li> </ul><li>More common in blacks than whites</li><li>Develops in the transitional and periurethral zones
<blockquote style="color: blue; ">BPH: periurethral/transitional zones</blockquote></li><li>DRE has a sensitivity of 50% in detecting BPH.</li><li>Approximately 30% of men with BPH have occult prostate cancer.</li> </ol><li>Pathogenesis</li><ol type="a"> <li>DHT is the primary mediator.
<blockquote style="color: blue; ">DHT: primary mediator for developing BPH; estrogen co-mediator</blockquote></li><ul> <li>Causes hyperplasia of glandular and stromal cells (see Fig. 1-14)</li> </ul><li>Stromal cells are the site of DHT synthesis.</li><li>Estrogen is a co-mediator.</li><ul> <li>Increases the synthesis of androgen receptors</li> </ul> </ol><li>Gross and microscopic findings</li><ol type="a"> <li>Hyperplasia of glandular cells and stromal cells</li><ul> <li>(1) Leads to nodule formation (<span>[[Fig. 20-8|Figure 20-8]]</span>)</li><li>(2) Nodules are yellow-pink and are soft.</li> </ul><li>Glandular hyperplasia develops nodules in the transitional zone.</li><li>Stromal hyperplasia develops nodules in the periurethral zone.</li><ul> <li>Most responsible for obstruction of the urethra</li> </ul> </ol><li>Clinical and laboratory findings</li><ol type="a"> <li>Signs of obstruction
<blockquote style="color: blue; ">Obstructive uropathy: most common complication of BPH; produces bladder diverticula</blockquote></li><ul> <li>(1) Trouble initiating and stopping the urinary stream</li><li>(2) Dribbling, incomplete emptying</li><li>(3) Nocturia, dysuria</li> </ul><li>Hematuria</li><li>Prostate-specific antigen (PSA; see later)</li><ul> <li>(1) Proteolytic enzyme</li><ul> <li>(a) Increases sperm motility</li><li>(b) Maintains seminal secretions in the liquid state</li> </ul><li>(2) PSA is usually normal (0-4 ng/mL) or between 4 and 10 ng/mL (30-50%)
<blockquote style="color: blue; ">BPH: 30% to 50% have ↑ PSA</blockquote></li><ul> <li>Rarely >10 ng/mL</li> </ul> </ul><li>Complications</li><ul> <li>(1) Obstructive uropathy</li><ul> <li>(a) Most common complication</li><li>(b) Postrenal azotemia</li><ul> <li>Potential for progressing to acute renal failure if left untreated</li> </ul><li>(c) Bilateral hydronephrosis
<blockquote style="color: blue; ">BPH: most common cause of bladder diverticula</blockquote></li><li>(d) Bladder diverticula from increased pressure</li><li>(e) Bladder wall smooth muscle hypertrophy</li> </ul><li>(2) Bladder infections due to residual urine</li><li>(3) Prostatic infarcts
<blockquote style="color: blue; ">Prostate infarct: pain on DRE; ↑ PSA</blockquote></li><ul> <li>(a) Pain on DRE</li><li>(b) Enlarged, indurated gland</li><li>(c) Increased PSA values due to infarction</li> </ul><li>(4) <i>No</i> risk for progression into carcinoma
<blockquote style="color: blue; ">BPH is <i>not</i> a risk factor for prostate cancer.</blockquote></li> </ul> </ol><li>Diagnosis</li><ol type="a"> <li>DRE is insensitive test.</li><li>Transrectal ultrasound if nodules palpated or increased PSA (see later discussion)</li> </ol><li>Treatment</li><ol type="a"> <li>Nonpharmacologic</li><ul> <li>Avoid caffeine or any other foods that exacerbate symptoms</li> </ul><li>General</li><ul> <li>(1) Medications</li><ul> <li>(a) α-adrenergic blockers
<blockquote style="color: blue; ">Rx of BPH: α-adrenergic blockers of smooth muscle</blockquote></li><ul> <li>Relax smooth muscle tone in capsule/bladder neck</li> </ul><li>(b) 5α-Reductase inhibitors</li><ul> <li>Block conversion of testosterone to DHT</li> </ul><li>(c) ? Usefulness of saw palmetto; 5α-reductase inhibitor</li> </ul><li>(2) Surgery
<blockquote style="color: blue; ">BPH surgery: TURP</blockquote></li><ul> <li>Transurethral resection of the prostate (TURP) is most commonly used.</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC020035"></a> <br><a name="P020034"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common cancer in adult males
<blockquote style="color: blue; ">Prostate cancer: most common cancer in men</blockquote></li><ul> <li>Second most common cancer-related death in adult males</li> </ul><li>Incidence increases with age</li><ul> <li>(1) Approximately 65% of all prostate cancers are diagnosed inmen ≥ 65 years old.</li><li>(2) Average age of diagnosis is 72 years old.</li> </ul><li>More common in blacks than whites</li><ul> <li>Rare in Asians</li> </ul><li>Usually asymptomatic until advanced</li><li>Peripheral in location
<blockquote style="color: blue; ">Prostate cancer: peripheral in location</blockquote></li><li>Risk factors</li><ul> <li>(1) Advancing age
<blockquote style="color: blue; ">Advancing age: greatest risk factor for prostate cancer</blockquote></li><ul> <li>Most important risk factor</li> </ul><li>(2) First-degree relatives (father and brothers)</li><li>(3) Black men</li><li>(4) Smoking cigarettes, high saturated fat diet</li> </ul> </ol><li>Pathogenesis</li><ul> <li>DHT-dependent
<blockquote style="color: blue; ">Prostate cancer: DHTdependent</blockquote></li> </ul><li>Gross and microscopic findings</li><ol type="a"> <li>Develops in the peripheral zone</li><ul> <li>(1) Palpable by DRE</li><li>(2) Obstructive uropathy is <i>not</i> an early finding.</li> </ul><li>Prostate intraepithelial neoplasia (PIN)</li><ul> <li>(1) Foci of atypia/dysplasia</li><li>(2) May be a precursor lesion for prostate cancer</li> </ul><li>Invasive cancer has a firm, gritty, yellow appearance (<span>[[Fig. 20-9|Figure 20-9]]</span>).</li><li>Hallmarks of malignancy</li><ul> <li>(1) Invasion of the capsule around the prostate</li><li>(2) Blood vessel/lymphatic invasion</li><li>(3) Perineural invasion</li><li>(4) Extension into the seminal vesicles or base of the bladder</li> </ul> </ol><li>Clinical findings in symptomatic prostate cancer
<blockquote style="color: blue; ">Prostate cancer: generally silent until advanced stage</blockquote></li><ol type="a"> <li>Generally silent until advanced stage</li><li>Obstructive uropathy implies extension into the bladder base</li><li>Low back/pelvic pain</li><ul> <li>(1) Portends bony metastases to vertebra and pelvic bones</li><ul> <li>Due to spread via the Batson venous plexus (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>)</li> </ul><li>(2) Alkaline phosphatase is increased.
<blockquote style="color: blue; ">Prostate cancer: osteoblastic metastases; lumbar spine, pelvis</blockquote></li><ul> <li>Due to osteoblastic metastases</li> </ul> </ul><li>Compression of the spinal cord</li> </ol><li>Diagnosis of prostate cancer</li><ol type="a"> <li>DRE negative in 10% of cases.</li><li>Screening</li><ul> <li>(1) DRE/PSA annually beginning at 50 years of age</li><li>(2) PSA is sensitive but <i>not</i> specific for cancer.
<blockquote style="color: blue; ">PSA: more sensitive than specific in prostate cancer</blockquote></li><ul> <li>BPH and prostatic infarcts can increase PSA, lowering its specificity by increasing false positive results.</li> </ul><li>(3) PSA > 10 ng/mL is highly predictive of cancer.</li><ul> <li>70% positive predictive value</li> </ul><li>(4) PSA between 4 and 10 ng/mL is a gray zone.</li><ul> <li>Overlap between early cancer and BPH</li> </ul><li>(5) Other more sensitive methods of reporting PSA</li><ul> <li>(a) Measurement of free versus bound forms of circulating PSA</li><ul> <li>Increased free levels are seen in BPH, while increased bound levels are seen in prostate cancer.
<blockquote style="color: blue; ">PSA: ↑ free PSA consider BPH; ↑ bound PSA consider prostate cancer</blockquote></li> </ul><li>(b) PSA doubling time</li><ul> <li>The shorter the doubling time, the more aggressive the tumor</li> </ul><li>(c) Rate of change of PSA values with time (PSA velocity)</li><ul> <li>Yearly PSA velocity > 0.75 ng/mL increases likelihood of developing prostate cancer if total serum PSA is normal.</li> </ul><li>(d) Age-adjustment of total serum PSA (controversial)</li><li>(e) Ratio between serum PSA and volume of the prostate gland (prostate density)</li> </ul> </ul> </ol><li>Spread of prostate cancer</li><ol type="a"> <li>Perineural invasion</li><li>Lymphatic spread to regional lymph nodes</li><li>Hematogenous spread</li><ul> <li>(1) Bone is the most common extranodal site (see Fig. 8-9)</li><ul> <li>In descending order-lumbar spine, proximal femur, and pelvis</li> </ul><li>(2) Lungs and liver</li> </ul> </ol><li>Diagnosis</li><ol type="a"> <li>Transrectal needle core biopsies of prostate; indications:
<blockquote style="color: blue; ">Diagnosis prostate cancer: transrectal needle core biopsies</blockquote></li><ul> <li>(1) Abnormal PSA value (see earlier)</li><li>(2) Abnormal DRE</li><li>(3) Previous diagnosis of atypia or carcinoma in situ</li> </ul> </ol><li>Imaging</li><ol type="a"> <li>Radionuclide bone scan</li><ul> <li>Evaluate bone metastasis</li> </ul><li>CT scan, MRI, transrectal ultrasound</li><ul> <li>Evaluate extent of disease</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Early disease</li><ul> <li>Surgery, external beam radiation, radioactive seed implants</li> </ul><li>Advanced disease</li><ul> <li>Hormonal therapy, chemotherapy, radiation, or combination</li> </ul> </ol><li>Prognosis
<blockquote style="color: blue; ">Prognosis: markedly improved because of early detection and improved treatment</blockquote></li><ol type="a"> <li>Dramatic increase in survival due to early detection and improved therapy</li><li>Five-year survival rate for all stages is almost 99%.</li><li>Ten-year relative survival rate is 91%.</li><li>Fifteen-year relative survival rate is 76%.</li> </ol> </ol>
</div></html>
![[20.VI.A.Clinical anatomy]]
<<tiddler [[20.VI.A.Clinical anatomy]]>>
![[20.VI.B.Acute/chronic prostatitis]]
<<tiddler [[20.VI.B.Acute/chronic prostatitis]]>>
![[20.VI.C.Benign prostatic hyperplasia (BPH)]]
<<tiddler [[20.VI.C.Benign prostatic hyperplasia (BPH)]]>>
![[20.VI.D.Prostate cancer]]
<<tiddler [[20.VI.D.Prostate cancer]]>>
<html><a name="HC020037"></a> <br><a name="P020039"></a><div class="PA" style="color: black; "><ol type="1"> <li>Follicle-stimulating hormone (FSH)</li><ol type="a"> <li>Stimulates spermatogenesis in the seminiferous tubules</li><li>Negative feedback relationship with inhibin
<blockquote style="color: blue; ">FSH: stimulates spermatogenesis</blockquote></li><ul> <li>(1) Inhibin is synthesized in Sertoli cells in seminiferous tubules.</li><li>(2) Decreased inhibin causes an increase in FSH.</li> </ul> </ol><li>Luteinizing hormone (LH)
<blockquote style="color: blue; ">LH: stimulates testosterone synthesis in Leydig cells</blockquote></li><ol type="a"> <li>Stimulates testosterone synthesis in the Leydig cells.</li><li>Testosterone has a negative feedback with LH.</li><ul> <li>Decreased testosterone causes an increase in LH.</li> </ul> </ol><li>Testosterone</li><ol type="a"> <li>Maintains male secondary sex characteristics</li><li>Enhances spermatogenesis in the seminiferous tubules
<blockquote style="color: blue; ">Testosterone: enhance spermatogenesis, libido</blockquote></li><li>Increases libido (sexual desire)</li><li>Decreased testosterone causes male hypogonadism and infertility.</li> </ol><li>Sex hormone-binding globulin (SHBG or androgen-binding globulin)</li><ol type="a"> <li>Binding protein for testosterone and estrogen</li><ul> <li>(1) In both men and women, SHBG is mainly synthesized in the liver.</li><li>(2) In men, the Sertoli cells also synthesize SHBG.
<blockquote style="color: blue; ">SHBG: synthesized in Sertoli cells and liver</blockquote></li><li>(3) Estrogen increases synthesis of SHBG in the liver.</li><li>(4) Androgens, insulin, obesity, and hypothyroidism all cause decreased synthesis of SHBG.</li> </ul><li>SHBG has a higher binding affinity for testosterone than estrogen.</li><ul> <li>"Estrogen amplifier"</li> </ul><ul> <li>(1) Increased SHBG decreases free testosterone levels.
<blockquote style="color: blue; ">↑ SHBG causes ↓ free testosterone</blockquote></li><li>(2) Decreased SHBG increases free testosterone levels.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC020038"></a> <br><a name="P020040"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">↓ SHBG causes ↑ free testosterone</blockquote>
<ol type="1"> <li>Decreased production of testosterone</li><ul> <li>Examples-hypopituitarism, Leydig cell dysfunction</li> </ul><li>Resistance to testosterone</li><ul> <li>Example-androgen receptor deficiency in testicular feminization</li> </ul> </ol>
</div></html>
<html><a name="HC020039"></a> <br><a name="PB020002"></a><div class="BB" style="color: rgb(47, 79, 79); ">Testosterone, per se, does <i>not</i> have any role in producing an erection (parasympathetic response) or ejaculation (sympathetic response). However, decreased testosterone decreases libido, which decreases psychic desire.
<blockquote style="color: blue; ">↓ Testosterone causes ↓ libido</blockquote></div><a name="P020041"></a><div class="PA" style="color: black; "><ol type="1"> <li>Impotence
<blockquote style="color: blue; ">Impotence: most common manifestation of male hypogonadism</blockquote></li><ol type="a"> <li>Most common manifestation</li><li>Failure to sustain an erection during attempted intercourse or during intercourse</li> </ol><li>Loss of male secondary sex characteristics</li><ol type="a"> <li>Estrogen activity is unopposed.</li><li>Findings include female hair distribution, gynecomastia</li> </ol><li>Osteoporosis
<blockquote style="color: blue; ">Hypogonadism: impotence, female secondary sex characteristics, osteoporosis</blockquote></li><ul> <li>Testosterone normally inhibits osteoclastic activity and increases osteoblastic activity.</li> </ul><li>Infertility</li><ul> <li>Decreased spermatogenesis</li> </ul> </ol>
</div></html>
<html><a name="HC020040"></a> <br><a name="P020042"></a><div class="PA" style="color: black; "><ol type="1"> <li>Primary hypogonadism</li><ul> <li>Due to Leydig cell dysfunction</li><ol type="a"> <li>LH is increased.</li><ul> <li>Loss of negative feedback imposed by testosterone</li> </ul><li>Hypergonadotropic (increased LH) hypogonadism
<blockquote style="color: blue; ">Primary hypogonadism: ↑ LH, ↓ testosterone</blockquote></li> </ol> </ul><li>Secondary hypogonadism</li><ul> <li>Due to hypothalamic/pituitary dysfunction</li><ol type="a"> <li>Decreased LH</li><li>Hypogonadotropic (decreased LH) hypogonadism
<blockquote style="color: blue; ">Secondary hypogonadism: ↓ LH, ↓ testosterone</blockquote></li> </ol> </ul> </ol>
</div></html>
<html><a name="HC020041"></a> <br><a name="P020043"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes</li><ol type="a"> <li>Chronic alcoholic liver disease</li><ul> <li>Inhibits binding of LH to Leydig cells (? mechanism)</li> </ul><li>Chronic renal failure</li><ul> <li>Toxins have a direct toxic effect on Leydig cell</li> </ul><li>Irradiation, orchitis, trauma
<blockquote style="color: blue; ">Primary hypogonadism, Leydig cell dysfunction: alcohol, renal failure, orchitis, radiation</blockquote></li> </ol><li>Laboratory findings in Leydig cell dysfunction</li><ol type="a"> <li>Decreased testosterone</li><ul> <li>Due to destruction of Leydig cells</li> </ul><li>Increased LH</li><ul> <li>Due to decreased testosterone</li> </ul><li>Decreased sperm count</li><ul> <li>Due to testosterone deficiency
<blockquote style="color: blue; ">Primary hypogonadism, Leydig cell dysfunction: ↓ testosterone, sperm count; ↑ LH; normal FSH</blockquote></li> </ul><li>Normal FSH</li><ul> <li>Inhibin is present in Sertoli cells.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC020042"></a> <br><a name="P020044"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes</li><ul> <li>Same causes as Leydig cell dysfunction</li> </ul><li>Laboratory findings</li><ol type="a"> <li>Decreased testosterone</li><ul> <li>Due to destruction of Leydig cells</li> </ul><li>Increased LH</li><ul> <li>Due to decreased testosterone</li> </ul><li>Decreased sperm count
<blockquote style="color: blue; ">Primary hypogonadism Leydig cell + seminiferous tubule dysfunction: ↓ testosterone, sperm count; ↑ LH; ↑ FSH</blockquote></li><ul> <li>Due to testosterone deficiency and seminiferous tubule dysfunction</li> </ul><li>Increased FSH</li><ul> <li>Due to decrease in inhibin</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC020043"></a> <br><a name="P020045"></a><div class="PA" style="color: black; "><ol type="1"> <li>Constitutional delay in puberty</li><ul> <li>A testicular volume > 4 mL indicates puberty has begun.</li> </ul><li>Kallmann's syndrome
<blockquote style="color: blue; ">Secondary hypogonadism causes: constitutional, Kallmann's syndrome, hypopituitarism</blockquote></li><ol type="a"> <li>Autosomal dominant disorder</li><li>Maldevelopment of the olfactory bulbs and GnRH-producing cells</li><li>Clinical findings</li><ul> <li>(1) Delayed puberty</li><li>(2) Anosmia, color blindness</li> </ul><li>Laboratory findings</li><ul> <li>Decreased FSH, LH, testosterone, and sperm count</li> </ul> </ol><li>Hypopituitarism (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li><ol type="a"> <li>Causes</li><ul> <li>(1) Craniopharyngioma in children
<blockquote style="color: blue; ">Secondary hypogonadism Kallmann's syndrome/hypopituitarism: ↓ testosterone, sperm count; ↓ LH; ↓ FSH</blockquote></li><li>(2) Nonfunctioning pituitary adenoma in adults</li> </ul><li>Laboratory findings</li><ul> <li>Decreased FSH, LH, testosterone, and sperm count</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC020044"></a><span>[[Table 20-2|Table 20-2. SUMMARY OF CAUSES OF MALE HYPOGONADISM]]</span> <br> <br> </html>
![[20.VII.A.Normal male reproductive physiology]]
<<tiddler [[20.VII.A.Normal male reproductive physiology]]>>
![[20.VII.B.Pathogenesis of male hypogonadism]]
<<tiddler [[20.VII.B.Pathogenesis of male hypogonadism]]>>
![[20.VII.C.Clinical presentations]]
<<tiddler [[20.VII.C.Clinical presentations]]>>
![[20.VII.D.Classification of male hypogonadism]]
<<tiddler [[20.VII.D.Classification of male hypogonadism]]>>
![[20.VII.E.Primary hypogonadism: Leydig cell dysfunction]]
<<tiddler [[20.VII.E.Primary hypogonadism: Leydig cell dysfunction]]>>
![[20.VII.F.Primary hypogonadism: Leydig cell and seminiferous tubule dysfunction]]
<<tiddler [[20.VII.F.Primary hypogonadism: Leydig cell and seminiferous tubule dysfunction]]>>
![[20.VII.G.Causes of secondary hypogonadism]]
<<tiddler [[20.VII.G.Causes of secondary hypogonadism]]>>
![[20.VII.H.Summary of causes of male hypogonadism (Table 20-2)]]
<<tiddler [[20.VII.H.Summary of causes of male hypogonadism (Table 20-2)]]>>
<html><a name="HC020046"></a> <br><a name="P020046"></a><div class="PA" style="color: black; "><ol type="1"> <li>Decreased sperm count</li><ol type="a"> <li>Primary testicular dysfunction</li><ul> <li>(1) Leydig cell dysfunction (refer to section VII)</li><li>(2) Seminiferous tubule dysfunction
<blockquote style="color: blue; ">Seminiferous tubule dysfunction: accounts for ∼90% of cases of male infertility</blockquote></li><ul> <li>(a) Causes</li><ul> <li>Varicocele (refer to section V), Klinefelter's syndrome (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>), orchitis</li> </ul><li>(b) Normal testosterone and LH</li><ul> <li>Leydig cells are intact.</li> </ul><li>(c) Decreased sperm count</li><ul> <li>Loss of seminiferous tubules and decreased testosterone</li> </ul><li>(d) Increased FSH</li><ul> <li>Inhibin is decreased.</li> </ul> </ul> </ul><li>Secondary hypogonadism</li><ul> <li>Pituitary and hypothalamic dysfunction (refer to section VII)
<blockquote style="color: blue; ">End-organ dysfunction: obstruction of vas deferens</blockquote></li> </ul> </ol><li>End-organ dysfunction</li><ol type="a"> <li>Causes</li><ul> <li>(1) Obstruction of vas deferens</li><li>(2) Disorders involving accessory sex organs or ejaculation</li> </ul><li>Normal testosterone, FSH, LH, prolactin</li><li>Sperm count variable</li> </ol> </ol>
</div></html>
<html><a name="HC020047"></a> <br><a name="P020047"></a><div class="PA" style="color: black; "><ol type="1"> <li>Semen analysis
<blockquote style="color: blue; ">Semen analysis: gold standard test for infertility</blockquote></li><ol type="a"> <li>Gold standard test for infertility</li><li>Components of semen</li><ul> <li>(1) Spermatozoa derive from the seminiferous tubules.</li><li>(2) Coagulant derives from the seminal vesicles.</li><li>(3) Enzymes to liquefy semen derive from the prostate gland.</li> </ul><li>Components evaluated in a standard semen analysis</li><ul> <li>(1) Volume</li><ul> <li>Volume does <i>not</i> correlate with the number of sperm.</li> </ul><li>(2) Sperm count</li><ul> <li>Normal is 20 to 150 million sperm/mL.</li> </ul><li>(3) Sperm morphology</li><ul> <li>Morphology is very abnormal in reconnections of a vasectomy.</li> </ul><li>(4) Sperm motility</li> </ul> </ol><li>Serum gonadotropins, testosterone, prolactin</li> </ol>
</div></html>
![[20.VIII.A.Epidemiology and pathogenesis]]
<<tiddler [[20.VIII.A.Epidemiology and pathogenesis]]>>
![[20.VIII.B.Laboratory tests for male infertility]]
<<tiddler [[20.VIII.B.Laboratory tests for male infertility]]>>
![[21.I.A.21.I.Sexually Transmitted Diseases and Other Genital Infections]]
<<tiddler [[21.I.A.21.I.Sexually Transmitted Diseases and Other Genital Infections]]>>
<html><a name="HC021003"></a> <br><a name="P021002"></a><div class="PA" style="color: black; "><ul> <li>Most often caused by <i>Neisseria gonorrhoeae</i></li> </ul>
</div></html>
<html><a name="HC021004"></a> <br><a name="P021003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Lichen sclerosis (<span>[[Fig. 21-2|Figure 21-2]]</span>)</li><ol type="a"> <li>Usually occurs in postmenopausal women
<blockquote style="color: blue; ">Lichen sclerosis: thin epidermis; parchment-like skin</blockquote></li><li>Thinning of the epidermis</li><ul> <li>Parchment-like appearance of skin</li> </ul><li>Small risk for developing squamous cell carcinoma</li> </ol><li>Lichen simplex chronicus</li><ol type="a"> <li>White plaque-like lesion (leukoplakia)
<blockquote style="color: blue; ">Lichen simplex: leukoplakia (hyperplasia)</blockquote></li><ul> <li>Due to squamous cell hyperplasia</li> </ul><li>Small risk for developing squamous cell carcinoma</li> </ol> </ol>
</div></html>
<html><a name="HC021005"></a> <br><a name="P021004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Papillary hidradenoma
<blockquote style="color: blue; ">Papillary hidradenoma: painful apocrine gland tumor</blockquote></li><ol type="a"> <li>Benign tumor of the apocrine sweat gland</li><li>Painful nodule on the labia majora</li> </ol><li>Vulvar intraepithelial neoplasia (VIN)</li><ol type="a"> <li>Dysplasia ranges from mild to carcinoma in situ</li><li>Strong human papillomavirus (HPV) type 16 association
<blockquote style="color: blue; ">VIN: HPV 16 association</blockquote></li><li>Precursor for developing squamous cell carcinoma</li> </ol><li>Squamous cell carcinoma</li><ol type="a"> <li>Most common cancer</li><li>Risk factors</li><ul> <li>(1) HPV type 16</li><li>(2) Smoking cigarettes</li><li>(3) Immunodeficiency (e.g., AIDS)</li> </ul><li>Metastasize first to the inguinal nodes</li> </ol><li>Extramammary Paget's disease</li><ol type="a"> <li>Red, crusted vulvar lesion</li><li>Intraepithelial adenocarcinoma
<blockquote style="color: blue; ">Extramammary Paget's disease: intraepithelial adenocarcinoma; PAS positive</blockquote></li><ul> <li>(1) Tumor derives from primitive epithelial progenitor cells.</li><li>(2) Malignant Paget's cells contain mucin (<span>[[Fig. 21-3|Figure 21-3]]</span>).</li><ul> <li>Mucin is periodic acid-Schiff (PAS) positive.</li> </ul><li>(3) Spreads along the epithelium</li><ul> <li>Rarely invades the dermis</li> </ul> </ul> </ol><li>Malignant melanoma</li><ol type="a"> <li>Melanoma cells are histologically similar to Paget's cells.</li><li>Unlike Paget's cells, melanoma cells are PAS negative.
<blockquote style="color: blue; ">Melanoma: PAS negative</blockquote></li> </ol> </ol>
</div></html>
![[21.II.A.Bartholin gland abscess]]
<<tiddler [[21.II.A.Bartholin gland abscess]]>>
![[21.II.B.Non-neoplastic dermatoses]]
<<tiddler [[21.II.B.Non-neoplastic dermatoses]]>>
![[21.II.C.Benign and malignant tumors]]
<<tiddler [[21.II.C.Benign and malignant tumors]]>>
<html><a name="HC021007"></a> <br><a name="P021008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Absence of the upper vagina and uterus
<blockquote style="color: blue; ">RKH syndrome: absence of upper vagina/uterus</blockquote></li><li>Anatomic cause of primary amenorrhea</li> </ol>
</div></html>
<html><a name="HC021008"></a> <br><a name="P021009"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Gartner's cyst: wolffian duct remnant</blockquote>
<ol type="1"> <li>Remnant of the wolffian (mesonephric) duct</li><li>Presents as a cyst on the lateral wall of the vagina</li> </ol>
</div></html>
<html><a name="HC021009"></a> <br><a name="P021010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Rhabdomyoma</li><ol type="a"> <li>Benign tumor of skeletal muscle</li><li>Other locations are the tongue and heart.</li> </ol><li>Embryonal rhabdomyosarcoma
<blockquote style="color: blue; ">Embryonal rhabdomyosarcoma: grape-like mass protruding from vagina</blockquote></li><ol type="a"> <li>Occurs in girls < 5 years old</li><li>Necrotic, grape-like mass protrudes from the vagina (<span>[[Fig. 21-4|Figure 21-4]]</span>).</li> </ol><li>Clear cell adenocarcinoma of the vagina (<span>[[Fig. 21-5|Figure 21-5]]</span>)</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Occurs in women with intrauterine exposure to diethylstilbestrol (DES)</li><ul> <li>DES was used to prevent a threatened abortion.</li> </ul><li>(2) DES inhibits müllerian differentiation.
<blockquote style="color: blue; ">DES: inhibits müllerian differentiation</blockquote></li><ul> <li>Müllerian structures: tubes, uterus, cervix, upper third of vagina</li> </ul><li>(3) Vaginal adenosis</li><ul> <li>(a) Remnants of müllerian glands</li><ul> <li>Produces red, superficial ulcerations in the upper portion of the vagina
<blockquote style="color: blue; ">Vaginal adenosis: red, superficial ulcerations</blockquote></li> </ul><li>(b) Precursor lesion for clear cell adenocarcinoma
<blockquote style="color: blue; ">Clear cell adenocarcinoma of vagina/cervix: associated with DES exposure; adenosis precursor lesion</blockquote></li> </ul><li>(4) Small risk for developing the cancer (1:1000)</li><li>(5) Cancer may involve upper vagina or cervix.</li> </ul><li>Other DES abnormalities</li><ul> <li>(1) Abnormally shaped uterus that thwarts implantation</li><li>(2) Cervical incompetence
<blockquote style="color: blue; ">Other DES abnormalities: incompetent cervix; abnormal uterine shape</blockquote></li><ul> <li>Common cause of recurrent abortions</li> </ul> </ul> </ol><li>Vaginal squamous cell carcinoma</li><ol type="a"> <li>Primary squamous cell carcinoma has an HPV type 16 association.</li><li>Most cancers are an extension of a cervical squamous cancer into the vagina.</li> </ol> </ol>
</div></html>
![[21.III.A.Rokitansky-Kuster-Hauser (RKH) syndrome]]
<<tiddler [[21.III.A.Rokitansky-Kuster-Hauser (RKH) syndrome]]>>
![[21.III.B.Gartner's duct cyst]]
<<tiddler [[21.III.B.Gartner's duct cyst]]>>
![[21.III.C.Benign and malignant tumors]]
<<tiddler [[21.III.C.Benign and malignant tumors]]>>
<html><a name="HC021011"></a> <br><a name="P021011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Cervix includes the endocervix + exocervix</li><ul> <li>The exocervix begins at the cervical os.</li> </ul><li>Exocervix is normally lined by squamous epithelium.</li><li>Endocervical glands are normally lined by mucus-secreting columnar cells.</li><li>Endocervical epithelium normally migrates down to the exocervix.</li><ol type="a"> <li>Exposure to the acid pH of the vagina produces squamous metaplasia.</li><li>The area undergoing metaplasia is called the transformation zone.</li><ul> <li>(1) This zone is where squamous dysplasia and cancer develop.
<blockquote style="color: blue; ">Transformation zone: site where squamous dysplasia and cancer develop</blockquote></li><li>(2) It must be sampled when performing a cervical Papanicolaou (Pap) smear.</li> </ul><li>Metaplastic squamous cells block endocervical gland orifices.</li><ul> <li>(1) Obstruction of outflow of mucus produces nabothian cysts (see <span>[[Fig. 21-17|Figure 21-17]]</span>).</li><li>(2) Nabothian cysts are a normal finding in adult women.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021012"></a> <br><a name="P021012"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Accounts for 20% to 25% of patients presenting with vaginal discharge</li><li>Can be found in any sexually active woman</li><li>Subdivided into acute and chronic cervicitis</li> </ol><li>Acute cervicitis</li><ol type="a"> <li>Acute inflammation is normally present in the transformation zone.</li><li>Pathologic acute cervicitis; causative agents:</li><ul> <li><i>Chlamydia trachomatis, N. gonorrhoeae, Trichomonas vaginalis, Candida</i>, herpes simplex virus (HSV-2), HPV</li> </ul><li>Clinical findings</li><ul> <li>(1) Vaginal discharge (most common)
<blockquote style="color: blue; ">Acute cervicitis: vaginal discharge most common complaint</blockquote></li><li>(2) Pelvic pain</li><li>(3) Dyspareunia</li><li>(4) Painful on palpation</li><li>(5) Bleeds easily when obtaining cultures</li><li>(6) Cervical os is erythematous and may be covered by an exudate.</li> </ul><li>Diagnosis</li><ul> <li>(1) DNA probe for <i>Chlamydi</i>a and <i>Neisseria gonorrhoeae</i></li><ul> <li>These organisms account for >50% of acute cervicitis.
<blockquote style="color: blue; ">Acute cervicitis: <i>C. trachomatis</i> and <i>N. gonorrhoeae</i> > 50% of cases</blockquote></li> </ul><li>(2) Wet mount for <i>Trichomonas</i></li><li>(3) Obtain a cervical Pap smear</li> </ul><li>Treatment</li><ul> <li>(1) If culture or DNA probe positive, treat with appropriate antibiotic.</li><li>(2) If culture negative, cryosurgery is an option.</li><li>(3) Advise safe sex with the use of condoms</li> </ul> </ol><li>Chronic cervicitis</li><ul> <li>Occurs when acute cervicitis persists</li> </ul><li>Follicular cervicitis
<blockquote style="color: blue; ">Follicular cervicitis: caused by <i>C. trachomatis</i></blockquote></li><ol type="a"> <li>Caused by <i>C. trachomatis</i></li><li>Pronounced lymphoid infiltrate with germinal centers</li><li><i>Chlamydia</i> infects metaplastic squamous cells.</li><ul> <li>(1) Cells contain vacuoles with red inclusions (reticulate bodies).
<blockquote style="color: blue; ">Reticulate bodies: produce elementary bodies, the infective particle of <i>Chlamydia</i></blockquote></li><li>(2) Reticulate bodies develop into elementary bodies, which are infective particles.</li> </ul><li>Cervicitis is the primary source for conjunctivitis and pneumonia in newborns.</li> </ol> </ol>
</div></html>
<html><a name="HC021013"></a> <br><a name="PB021001"></a><div class="BB" style="color: rgb(47, 79, 79); ">Because the transformation zone is the site for squamous dysplasia and squamous cancer, it must be adequately sampled. The presence of metaplastic squamous cells or mucus-secreting columnar cells indicates proper sampling. Absence of these cells means that the Pap smear must be repeated.
<blockquote style="color: blue; ">Superficial squamous cells: adequate estrogen</blockquote></div><a name="P021013"></a><div class="PA" style="color: black; "><ol type="1"> <li>Purpose</li><ol type="a"> <li>Screening test to rule out squamous dysplasia and cancer
<blockquote style="color: blue; ">Cervical Pap smear: screen for dysplasia/cancer, evaluates hormonal status</blockquote></li><li>To evaluate the hormone status of the patient</li> </ol><li>Sample sites</li><ul> <li>Vagina, exocervix, transformation zone</li> </ul><li>Interpretation of the Pap smear</li><ol type="a"> <li>Superficial squamous cells indicate adequate estrogen.
<blockquote style="color: blue; ">Intermediate squamous cells: adequate progesterone</blockquote></li><li>Intermediate squamous cells indicate adequate progesterone.</li><li>Parabasal cells indicate a lack of estrogen and progesterone.</li><li>Normal nonpregnant adult woman
<blockquote style="color: blue; ">Parabasal cells: lack of estrogen and progesterone</blockquote></li><ul> <li>70% superficial squamous cells, 30% intermediate squamous cells</li> </ul><li>Pregnant woman</li><ul> <li>100% intermediate squamous cells from progesterone effect</li> </ul><li>Elderly woman with lack of estrogen and progesterone</li><ul> <li>Atrophic smear with parabasal cells and inflammation</li> </ul><li>Woman with continuous exposure to estrogen without progesterone</li><ul> <li>100% superficial squamous cells</li> </ul> </ol> </ol>
</div></html>
![[21.IV.A.Clinical anatomy and histology]]
<<tiddler [[21.IV.A.Clinical anatomy and histology]]>>
![[21.IV.B.Acute and chronic cervicitis]]
<<tiddler [[21.IV.B.Acute and chronic cervicitis]]>>
![[21.IV.C.Cervical Pap smear]]
<<tiddler [[21.IV.C.Cervical Pap smear]]>>
![[21.IV.D.Cervical (endocervical) polyp]]
<<tiddler [[21.IV.D.Cervical (endocervical) polyp]]>>
![[21.IV.E.Cervical intraepithelial neoplasia (CIN)]]
<<tiddler [[21.IV.E.Cervical intraepithelial neoplasia (CIN)]]>>
![[21.IV.F.Cervical cancer]]
<<tiddler [[21.IV.F.Cervical cancer]]>>
<html><a name="HC021014"></a> <br><a name="P021014"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Cervical polyp: non-neoplastic</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Non-neoplastic polyp that protrudes from the cervical os</li><li>Arises from the endocervix, <i>not</i> the cervix</li><li>Most commonly present in perimenopausal women and multigravida women</li><li>Most commonly occur between 30 and 50 years of age</li><li><i>Not</i> precancerous</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Essentially unknown</li><li>Inflammation, trauma, pregnancy have been implicated.</li> </ol><li>Clinical findings
<blockquote style="color: blue; ">Cervical polyp: postcoital bleeding; vaginal discharge</blockquote></li><ol type="a"> <li>Postcoital bleeding</li><li>Vaginal discharge</li> </ol><li>Treatment is surgical excision.</li> </ol>
</div></html>
<html><a name="HC021015"></a> <br><a name="P021015"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology
<blockquote style="color: blue; ">CIN: most cases associated with HPV; smoking is risk factor</blockquote></li><ol type="a"> <li>Majority of cases are associated with HPV.</li><ul> <li>(1) Low risk-types 6, 11</li><li>(2) High risk-types 16, 18</li><li>(3) HPV produces koilocytosis in squamous cells (<span>[[Fig. 21-6|Figure 21-6]]</span>).</li><ul> <li>Clear halo containing a wrinkled, pyknotic nucleus
<blockquote style="color: blue; ">Koilocytosis: HPV effect in squamous cells</blockquote></li> </ul> </ul><li>Peak incidence is 35 years of age.</li><li>False negative rate on detecting dysplasia on a cervical Pap smear is ∼40%.</li><li>Risk factors</li><ul> <li>(1) Early age of onset of sexual intercourse</li><li>(2) Multiple, high-risk partners</li><li>(3) High-risk types of HPV in a biopsy</li><li>(4) Smoking, oral contraceptive pills (OCPs)</li><li>(5) Immunodeficiency</li> </ul> </ol><li>Classification of CIN
<blockquote style="color: blue; ">Cervical dysplasia: precursor for squamous cancer</blockquote></li><ol type="a"> <li>CIN I</li><ul> <li>Mild dysplasia involving the lower third of the epithelium</li> </ul><li>CIN II</li><ul> <li>Moderate dysplasia involving the lower two thirds of the epithelium</li> </ul><li>CIN III (see Fig. 1-17)</li><ul> <li>Severe dysplasia to carcinoma in situ (CIS) involving the full thickness of the epithelium</li> </ul> </ol><li>Progression from CIN I to CIN III is <i>not</i> inevitable.</li><ol type="a"> <li>Reversal to normal is more likely in CIN I.</li><li>Requires ∼10 years to progress from CIN I to CIN III</li><li>Requires ∼10 years to progress from CIN III to invasive cancer</li><ul> <li>Average age for cervical cancer is ∼45 years old.</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Dysplasia is <i>not</i> usually visible to naked eye; colposcopy is required.</li><ul> <li>Occasionally, flat to warty appearing condyloma acuminata are visible.</li> </ul><li>Colposcopy findings, after application of acetic acid:</li><ul> <li>Acetowhite areas with punctation, mosaic pattern, or abnormal vascularity</li> </ul> </ol><li>Treatment</li><ul> <li>Electrocoagulation, cryotherapy, laser ablation, local surgery (conization)</li> </ul> </ol>
</div></html>
<html><a name="HC021016"></a> <br><a name="P021016"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Least common gynecologic cancer
<blockquote style="color: blue; ">Cervical cancer: least common gynecologic cancer; importance of Pap smear</blockquote></li><ul> <li>Due to early detection of CIN with Pap smears</li> </ul><li>Higher incidence in developing countries</li><li>In U.S. population incidence in descending order:</li><ul> <li>Hispanic, black, white</li> </ul><li>Majority are squamous cell carcinoma (75-80% of cases).</li><ul> <li>Small cell cancer and adenocarcinoma are less common types.</li> </ul><li>Cause and risk factors</li><ul> <li>Same as those listed for CIN</li> </ul> </ol><li>Clinical findings (<span>[[Figs. 21-7|Figure 21-7]]</span> and <span>[[21-8|Figure 21-8]]</span>)</li><ol type="a"> <li>Abnormal vaginal bleeding (most common)
<blockquote style="color: blue; ">Cervical cancer: abnormal vaginal bleeding most common sign</blockquote></li><ul> <li>Usually postcoital</li> </ul><li>Malodorous discharge</li><li>Postcoital bleeding</li> </ol><li>Cancer characteristics</li><ol type="a"> <li>Extends down into the vagina</li><li>Extends out into the lateral wall of the cervix and vagina</li><li>Infiltrates the bladder wall and obstructs the ureters</li><ul> <li>Postrenal azotemia leading to renal failure is a common cause of death.
<blockquote style="color: blue; ">Cervical cancer: renal failure is a common cause of death.</blockquote></li> </ul><li>Distant metastases (e.g., lungs)</li> </ol><li>Treatment of invasive cancer</li><ol type="a"> <li>Surgery, radiation, or both</li><li>Chemotherapy in selected cases</li> </ol><li>Prognosis</li><ul> <li>The 1- and 5-year relative survival rates are 88% and 72%, respectively.</li> </ul> </ol>
</div></html>
<html><a name="HC021051"></a> <br><a name="P021069"></a><div class="PA" style="color: black; "><ol type="1"> <li>Fetal surface (<span>[[Fig. 21-26A|Figure 21-26]]</span>)</li><ol type="a"> <li>Entirely covered by the chorionic plate
<blockquote style="color: blue; ">Fetal surface: chorionic plate</blockquote></li><li>Chorionic villi vessels converge with the umbilical cord.</li><li>Chorion is covered by the amnion.</li> </ol><li>Maternal surface (<span>[[Fig. 21-26B|Figure 21-26]]</span>)
<blockquote style="color: blue; ">Maternal surface: cotyledons</blockquote></li><ul> <li>Contains cotyledons covered by a layer of decidua basalis</li> </ul><li>Chorionic villus/umbilical cord</li><ol type="a"> <li>Chorionic villi project in the intervillous space (<span>[[Fig. 21-27|Figure 21-27]]</span>).
<blockquote style="color: blue; ">Chorionic villi: extract O<sub>2</sub> from maternal blood</blockquote></li><ul> <li>(1) Space contains maternal blood from which oxygen is extracted.</li><li>(2) Spiral arteries from the uterus empty into the space.</li> </ul><li>Chorionic villi are lined by trophoblastic tissue.
<blockquote style="color: blue; ">Trophoblast: lines villi; syncytiotrophoblast (synthesizes hCG, HPL) and cytotrophoblast</blockquote></li><ul> <li>(1) Outside layer is composed of syncytiotrophoblast.</li><ul> <li>(a) Synthesizes hCG (see earlier discussion)</li><li>(b) Synthesizes human placental lactogen (HPL)</li><ul> <li>Directly correlates with placental mass and has anti-insulin activity
<blockquote style="color: blue; ">HPL: directly correlates with placental mass, anti-insulin activity</blockquote></li> </ul> </ul><li>(2) Inside layer is composed of cytotrophoblast.</li> </ul><li>Chorionic villus vessels coalesce to form the umbilical vein.</li><li>Umbilical cord</li><ul> <li>(1) Contains one umbilical vein and two umbilical arteries
<blockquote style="color: blue; ">Umbilical cord: 2 arteries, 1 vein; umbilical vein has most O<sub>2</sub></blockquote></li><ul> <li>Umbilical vein contains oxygenated blood.</li> </ul><li>(2) Single umbilical artery</li><ul> <li>(a) Increased incidence of congenital anomalies (20% of cases)</li><li>(b) Defects-cardiovascular; trisomy 18; esophageal atresia</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC021052"></a> <br><a name="P021070"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most are due to ascending bacterial infections</li><ul> <li>(1) Complication of premature rupture of membranes</li><ul> <li>If culture is negative for group B streptococcus, treat prophylactically with IV ampicillin + IV erythromycin followed by amoxicillin + erythromycin by mouth
<blockquote style="color: blue; ">Placenta infections: group B streptococcus most common</blockquote></li> </ul><li>(2) Group B streptococcus is common pathogen.</li><ul> <li>If culture is positive during labor, treat with penicillin G or ampicillin IV.</li> </ul><li>(3) Other pathogens-<i>B. fragilis, Prevotella bivius</i>, group A streptococcus</li> </ul><li>Congenital infections (e.g., cytomegalovirus, syphilis)</li> </ol><li>Funisitis and placentitis</li><ul> <li>Infection of the umbilical cord and placenta, respectively</li> </ul><li>Chorioamnionitis
<blockquote style="color: blue; ">Chorioamnionitis: infection fetal membranes; danger neonatal sepsis/meningitis</blockquote></li><ol type="a"> <li>Infection of the fetal membranes</li><li>Danger of neonatal sepsis and meningitis</li><li>Treatment</li><ul> <li>Cefoxitin; ticarcillin-clavulanate</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021053"></a> <br><a name="P021071"></a><div class="PA" style="color: black; "><ol type="1"> <li>Placenta previa (<span>[[Fig. 21-28|Figure 21-28]]</span>)
<blockquote style="color: blue; ">Placenta previa: implantation over cervical os; previous C-section risk factor</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Implantation over cervical os</li><li>(2) Previous cesarean section is a risk factor (approaches 10%).</li> </ul><li>Clinical findings</li><ul> <li>(1) Presents with painless vaginal bleeding
<blockquote style="color: blue; ">Placenta previa: painless vaginal bleeding</blockquote></li><ul> <li>Usually in second or third trimester</li> </ul><li>(2) Uterus soft and nontender</li><li>(3) Fetal distress usually not present.</li> </ul><li>Diagnosis</li><ul> <li>(1) Pelvic examination should <i>not</i> be performed.
<blockquote style="color: blue; ">Placenta previa: do not perform pelvic exam; diagnose by ultrasound</blockquote></li><li>(2) Transabdominal ultrasound localizes placenta.</li><li>(3) Transvaginal ultrasound confirms placenta previa.</li> </ul><li>Treatment</li><ul> <li>(1) Careful observation of fetus and mother</li><li>(2) Delivery by cesarean section</li> </ul> </ol><li>Abruptio placentae (<span>[[Fig. 21-29|Figure 21-29]]</span>)
<blockquote style="color: blue; ">Abruptio placentae: retroplacental clot</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Premature separation of placenta due to formation of a retroplacental clot</li><ul> <li>(a) Separates the placenta from the implantation site</li><li>(b) Most common cause of late pregnancy bleeding
<blockquote style="color: blue; ">Abruptio placentae: most common cause of late pregnancy bleeding</blockquote></li><li>(c) Occurs in 1:830 pregnancies</li> </ul><li>(2) Fetal mortality rate is 20% to 40%.</li><li>(3) Risk factors</li><ul> <li>(a) Hypertension (greatest risk factor; 40-50% of cases)
<blockquote style="color: blue; ">Abruptio placentae: hypertension greatest risk factor</blockquote></li><li>(b) Smoking cigarettes</li><li>(c) Cocaine addiction; advanced maternal age</li><li>(d) Trauma; chorioamnionitis</li><li>(e) Premature rupture of membranes</li><li>(f) Previous abruptio placentae</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Painful uterine bleeding</li><ul> <li>Concealed (20%) or vaginal bleeding (80%)</li> </ul><li>(2) Forceful uterine contractions (∼15%) or signs of preterm labor
<blockquote style="color: blue; ">Abruptio placentae triad: painful vaginal bleeding, tetanic contractions, fetal compromise</blockquote></li><li>(3) Evidence of fetal distress is usually present.</li> </ul><li>Diagnosis</li><ul> <li>(1) Pelvic examination should <i>not</i> be done.</li><li>(2) Ultrasound</li> </ul><li>Treatment</li><ul> <li>(1) Fetal heart monitoring</li><li>(2) Monitor maternal hemodynamic status</li><li>(3) Deliver baby</li> </ul> </ol><li>Placenta accreta</li><ol type="a"> <li>Direct implantation into muscle <i>without</i> intervening decidua
<blockquote style="color: blue; ">Placenta accreta: implantation into muscle; danger of hemorrhage at delivery</blockquote></li><ul> <li>Occurs in 1:2500 pregnancies</li> </ul><li>Great risk for hemorrhage during delivery</li><li>Commonly requires surgery to control bleeding</li><ul> <li>Hysterectomy is often necessary.</li> </ul> </ol><li>Velamentous insertion</li><ol type="a"> <li>Umbilical cord inserts away from the placental edge.</li><ul> <li>Vessels pass to the placenta through the membranes between the amnion and the chorion.
<blockquote style="color: blue; ">Velamentous insertion: cord inserts away from placental edge; danger of tearing vessels</blockquote></li> </ul><li>Increased risk for hemorrhage if vessels are torn</li><li>Can be diagnosed by ultrasound</li><li>Often delivered by cesarean section to avoid vessel tear</li> </ol><li>Accessory lobes
<blockquote style="color: blue; ">Accessory lobe: increased risk for hemorrhage if detached</blockquote></li><ul> <li>Increased risk for hemorrhage if they are detached</li> </ul><li>Enlarged placenta</li><ol type="a"> <li>Diabetes mellitus</li><li>Rh hemolytic disease of newborn (HDN)
<blockquote style="color: blue; ">Enlarged placenta: Rh HDN, congenital syphilis, diabetes mellitus</blockquote></li><li>Congenital syphilis</li> </ol><li>Twin placentas (<span>[[Fig. 21-30|Figure 21-30]]</span>)</li><ol type="a"> <li>Monochorionic types are associated with identical twins.
<blockquote style="color: blue; ">Monochorionic twin placentas: identical twins, single fertilized egg</blockquote></li><ul> <li>(1) Identical twins derive from a single fertilized egg.</li><li>(2) Monoamniotic with a single amniotic sac (<span>[[Fig. 21-30A|Figure 21-30]]</span>)</li><ul> <li>Type for Siamese twins or tangling of umbilical cords</li> </ul><li>(3) Diamniotic with separate amniotic sacs (<span>[[Fig. 21-30B|Figure 21-30]]</span>)</li><li>(4) Fetal-to-fetal transfusion can occur in either type.</li> </ul><li>Dichorionic placentas
<blockquote style="color: blue; ">Dichorionic twin placentas: identical or fraternal (separate fertilized eggs)</blockquote></li><ul> <li>(1) Can be identical or fraternal twins</li><ul> <li>Fraternal twins occur when separate eggs are fertilized.</li> </ul><li>(2) Placentas can be diamniotic (<span>[[Fig. 21-30C|Figure 21-30]]</span>) or separated (<span>[[Fig. 21-30D|Figure 21-30]]</span>).</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021054"></a> <br><a name="P021072"></a><div class="PA" style="color: black; "><ul> <li>Toxemia of pregnancy</li><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Usually occurs in the third trimester (24th to 25th weeks)
<blockquote style="color: blue; ">Preeclampsia: usually occurs during third trimester</blockquote></li><li>Occurs in ∼6% of primigravidas and ∼7% of multigravidas</li><li>Risk factors</li><ul> <li>(1) More common in women < 20 years of age and >35 years of age</li><li>(2) History of previous preeclampsia</li><li>(3) Positive family history</li><li>(4) Multiple gestations</li><li>(5) Blacks</li><li>(6) Thrombocytosis; obesity</li> </ul><li>May be associated with hydatidiform moles (see later discussion)</li><ul> <li>(1) Complete mole, 2%</li><li>(2) Partial mole, 5%</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Abnormal placentation</li><ul> <li>(1) Causes mechanical or functional obstruction of the spiral arteries</li><li>(2) Abnormal trophoblastic tissue invades the spiral arteries.
<blockquote style="color: blue; ">Preeclampsia: placental hypoperfusion; vasoconstriction overrides vasodilation</blockquote></li> </ul><li>Imbalance favoring vasoconstrictors over vasodilators</li><ul> <li>(1) Normal vasodilators are decreased.</li><ul> <li>Examples-PGE<sub>2</sub>, nitric oxide</li> </ul><li>(2) Vasoconstrictors are increased.</li><ul> <li>(a) Examples-thromboxane A<sub>2</sub>, angiotensin II</li><li>(b) Increased sensitivity to the effect of angiotensin II</li> </ul><li>(3) Increase in various growth factors (e.g., vascular growth factor)</li> </ul><li>Net effect is placental hypoperfusion.</li> </ol><li>Pathologic findings
<blockquote style="color: blue; ">Preeclampsia: premature aging of placenta; placental infarctions</blockquote></li><ol type="a"> <li>Premature aging of the placenta</li><li>Multiple placental infarctions</li><li>Spiral arteries show intimal atherosclerosis.</li> </ol><li>Clinical and laboratory findings
<blockquote style="color: blue; ">Preeclampsia: hypertension, proteinuria, pitting edema</blockquote></li><ol type="a"> <li>Hypertension (increased vasoconstrictors)</li><ul> <li>Ranges from just below 140/90 mm Hg to >160/110 mm Hg</li> </ul><li>Proteinuria in nephrotic range (>3.5 g/24 hours)</li><ul> <li>Usually >5 g/24 hour urine collection</li> </ul><li>Dependent pitting edema</li><ul> <li>Due to loss of albumin in the urine</li> </ul><li>Weight gain > 4 pounds/week</li><ul> <li>Due to retention of sodium</li> </ul><li>Generalized seizures</li><ul> <li>(1) Preeclampsia + seizures is called eclampsia.</li><li>(2) Magnesium sulfate is used for treatment.</li> </ul><li>Renal disease</li><ul> <li>(1) Swollen endothelial cells in the glomerular capillaries</li><li>(2) Produces oliguria</li> </ul><li>Liver disease</li><ul> <li>(1) Right upper quadrant pain and hepatomegaly</li><li>(2) Periportal necrosis with increased transaminases</li> </ul><li>HELLP syndrome (refer to <span macro="tag [[18 Hepatobiliary and Pancreatic Disorders]] [[Chapter 18]]"></span>)</li><ul> <li>Hemolytic anemia and disseminated intravascular coagulation
<blockquote style="color: blue; ">Rx preeclampsia: delivery is treatment of choice; magnesium sulfate for seizures</blockquote></li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Delivery is the treatment of choice and the only cure for the disease.</li><li>Magnesium sulfate is given for seizures.</li> </ol> </ol> </ul>
</div></html>
<html><a name="HC021055"></a> <br><a name="P021073"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hydatidiform moles
<blockquote style="color: blue; ">Hydatidiform mole: benign tumor of chorionic villus</blockquote></li><ol type="a"> <li>Benign tumors of the chorionic villus</li><ul> <li>Complete and partial moles</li> </ul><li>More common at the extremes of age</li><li>Occurs in 1:1200 pregnancies in the United States</li><ul> <li>Occurs in 1:200 pregnancies in Indonesia</li> </ul><li>Complete mole is the most common type.</li><ul> <li>(1) The entire placenta is neoplastic.</li><li>(2) Dilated, swollen villi without fetal blood vessels (<span>[[Fig. 21-31|Figure 21-31]]</span>)
<blockquote style="color: blue; ">Complete mole: whole placenta is neoplastic; no embryo; 46,XX (both male Xs)</blockquote></li><li>(3) <i>No</i> embryo is present.</li><li>(4) 46,XX (90% of cases)</li><ul> <li>(a) Both chromosomes are of male origin.</li><li>(b) Egg is fertilized by two haploid spermatozoa with X chromosomes.</li> </ul><li>(5) Increased risk for developing choriocarcinoma (20% chance)</li><li>(6) Clinical findings</li><ul> <li>(a) Painless vaginal bleeding in fourth or fifth month of pregnancy</li><li>(b) Severe vomiting</li><li>(c) Preeclampsia is present in 2% of patients.
<blockquote style="color: blue; ">Complete mole: ultrasound with "snowstorm" appearance; too large for gastrointestinal age</blockquote></li><li>(d) Uterus is too large for gestational age.</li><li>(e) Increased hCG for the gestational age</li><li>(f) "Snowstorm appearance" with ultrasound (<span>[[Fig. 21-32|Figure 21-32]]</span>)</li> </ul><li>(7) Treatment</li><ul> <li>(a) Dilation and curettage</li><ul> <li>Must remove all material</li> </ul><li>(b) Follow patient with hCG levels</li><ul> <li>Should go down to zero</li> </ul> </ul> </ul><li>Partial mole</li><ul> <li>(1) Not all villi are neoplastic or dilated.
<blockquote style="color: blue; ">Partial mole: part of placenta neoplastic; embryo present; 69 chromosomes</blockquote></li><li>(2) Normal embryo is present (no chromosome abnormality).</li><ul> <li>(a) Triploid (69,XY)</li><li>(b) Egg with 23,X is fertilized by a 23,X and a 23,Y sperm.</li> </ul><li>(3) Preeclampsia in 5% of patients</li><li>(4) Low risk (2-3%) risk for developing a choriocarcinoma</li> </ul> </ol><li>Choriocarcinoma</li><ol type="a"> <li>Malignant tumor composed of syncytiotrophoblast and cytotrophoblast
<blockquote style="color: blue; ">Choriocarcinoma: malignancy of trophoblastic tissue; no chorionic villi</blockquote></li><ul> <li>Chorionic villi are <i>not</i> present.</li> </ul><li>Risk factors</li><ul> <li>(1) Complete mole (50% of cases)</li><li>(2) Spontaneous abortion (25% of cases)
<blockquote style="color: blue; ">Choriocarcinoma: complete mole (50%); spontaneous abortion (25%); normal pregnancy (25%)</blockquote></li><li>(3) Normal pregnancy (25% of cases)</li> </ul><li>Common sites of metastasis</li><ul> <li>(1) Lungs and vagina</li><li>(2) Lesions are hemorrhagic.</li> </ul><li>Excellent response to chemotherapy (methotrexate); low mortality rate</li><ul> <li>Good response does <i>not</i> apply to non-gestationally derived cancer.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021056"></a> <br><a name="P021074"></a><div class="PA" style="color: black; "><ol type="1"> <li>Composition</li><ol type="a"> <li>Predominantly fetal urine</li><li>High salt content causes ferning when dried on a slide.
<blockquote style="color: blue; ">Amniotic fluid: high salt content causing ferning when dried on glass slide</blockquote></li><ul> <li>Excellent sign of premature rupture of the amniotic sac</li> </ul><li>Swallowed and recycled by the fetus</li><li>Polyhydramnios
<blockquote style="color: blue; ">Polyhydramnios: TE fistula, duodenal atresia, maternal diabetes (fetal polyuria)</blockquote></li><ul> <li>(1) Excessive amniotic fluid</li><li>(2) Causes</li><ul> <li>(a) Tracheoesophageal (TE) fistula (refer to <span macro="tag [[17 Gastrointestinal Disorders]] [[Chapter 17]]"></span>)</li><li>(b) Duodenal atresia (refer to <span macro="tag [[17 Gastrointestinal Disorders]] [[Chapter 17]]"></span>)</li><li>(c) Maternal diabetes (20%)</li><ul> <li>Maternal hyperglycemia → fetal hyperglycemia → fetal polyuria</li> </ul> </ul> </ul><li>Oligohydramnios
<blockquote style="color: blue; ">Oligohydramnios: juvenile polycystic kidney disease</blockquote></li><ul> <li>(1) Decreased amount of amniotic fluid</li><li>(2) Causes</li><ul> <li>(a) Juvenile polycystic kidney disease (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)</li><li>(b) Fetal genitourinary obstruction</li><li>(c) Uteroplacental insufficiency</li><li>(d) Premature rupture of membranes</li> </ul> </ul> </ol><li>α-Fetoprotein (AFP) in pregnancy</li><ol type="a"> <li>Increased maternal AFP
<blockquote style="color: blue; ">Increased AFP in pregnancy: open neural tube defect</blockquote></li><ul> <li>(1) Open neural tube defect</li><li>(2) Related to folate deficiency</li><li>(3) Folate stores should be adequate <i>before</i> pregnancy.</li><ul> <li>Neural tube is already developed by the end of the first month of gestation.</li> </ul> </ul><li>Decreased maternal AFP</li><ul> <li>Down syndrome</li> </ul> </ol><li>Lecithin/sphingomyelin (L:S) ratio</li><ol type="a"> <li>Lecithin</li><ul> <li>(1) Synthesized by type II pneumocytes</li><li>(2) Decreases alveolar surface tension to prevent atelectasis</li> </ul><li>L:S ratio greater than 2 in amniotic fluid indicates adequate surfactant.
<blockquote style="color: blue; ">L:S ratio > 2: adequate surfactant</blockquote></li><li>Cortisol and thyroxine increase surfactant synthesis.</li><ul> <li>Maternal administration of glucocorticoids increases surfactant synthesis if babies must be delivered before term.</li> </ul><li>Insulin inhibits surfactant synthesis.</li> </ol> </ol>
</div></html>
<html><a name="HC021057"></a> <br><a name="P021075"></a><div class="PA" style="color: black; "><ol type="1"> <li>Derived from the fetal adrenal gland, placenta, and maternal liver
<blockquote style="color: blue; ">Estriol: derived from fetal adrenal gland, placenta, maternal liver</blockquote></li><ol type="a"> <li>Fetal zone of the adrenal cortex</li><ul> <li>(1) Converts pregnenolone synthesized in the placenta to DHEA-sulfate</li><li>(2) Fetal zone is absent in anencephaly (absent brain).</li> </ul><li>Fetal liver</li><ul> <li>DHEA-sulfate is 16-hydroxylated to 16-OH-DHEA-sulfate.</li> </ul><li>Maternal placenta</li><ul> <li>(1) Placental sulfatase cleaves off the sulfate from 16-OH-DHEA-sulfate.</li><li>(2) 16-OH-DHEA is converted by aromatase to free unbound estriol.</li> </ul><li>Maternal liver</li><ul> <li>(1) Free estriol is conjugated to estriol sulfate and estriol glucosiduronate.</li><li>(2) Both compounds are excreted in maternal urine and bile.</li> </ul> </ol><li>Decreased levels of estriol
<blockquote style="color: blue; ">Decreased estriol: fetal-maternal-placental dysfunction</blockquote></li><ul> <li>Sign of fetal-maternal-placental dysfunction</li> </ul><li>Down syndrome triad</li><ol type="a"> <li>Decreased urine estriol
<blockquote style="color: blue; ">Down syndrome triad:↓ urine estriol, serum AFP; ↑ serum hCG</blockquote></li><li>Decreased serum AFP</li><li>Increased serum β-hCG</li> </ol> </ol>
</div></html>
![[21.IX.A.Placental anatomy]]
<<tiddler [[21.IX.A.Placental anatomy]]>>
![[21.IX.B.Placental infections]]
<<tiddler [[21.IX.B.Placental infections]]>>
![[21.IX.C.Selected placental abnormalities]]
<<tiddler [[21.IX.C.Selected placental abnormalities]]>>
![[21.IX.D.Preeclampsia/eclampsia]]
<<tiddler [[21.IX.D.Preeclampsia/eclampsia]]>>
![[21.IX.E.Gestational trophoblastic neoplasms]]
<<tiddler [[21.IX.E.Gestational trophoblastic neoplasms]]>>
![[21.IX.F.Amniotic fluid]]
<<tiddler [[21.IX.F.Amniotic fluid]]>>
![[21.IX.G.Urine estriol in pregnancy]]
<<tiddler [[21.IX.G.Urine estriol in pregnancy]]>>
<html><a name="HC021018"></a> <br><a name="P021020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Breast budding (thelarche)</li><li>Growth spurt</li><li>Pubic hair
<blockquote style="color: blue; ">Sequence to menarche: breast budding, growth spurt, pubic hair, axillary hair, menarche</blockquote></li><li>Axillary hair</li><li>Menarche</li><ol type="a"> <li>Mean age of 12.8 years</li><li>Anovulatory cycles for 1-1.5 years</li> </ol> </ol>
</div></html>
<html><a name="HC021019"></a> <br><a name="PB021002"></a><div class="BB" style="color: rgb(47, 79, 79); ">In fertility workups, endometrial biopsies are commonly performed on day 21 to see if ovulation has occurred. Presence of secretory endometrium on day 21 confirms that ovulation has occurred.</div><a name="P021021"></a><div class="PA" style="color: black; "><ul> <li>Synthesis of sex hormones in the ovary (<span>[[Fig. 21-9|Figure 21-9]]</span>)</li><ol type="1"> <li>Proliferative (follicular) phase (<span>[[Fig. 21-10|Figure 21-10]]</span>)
<blockquote style="color: blue; ">Proliferative phase: estrogen-mediated; most variable phase</blockquote></li><ol type="a"> <li>Estrogen-mediated proliferation of glands</li><ul> <li><i>Most</i> variable phase of the cycle</li> </ul><li>Estrogen surge occurs 24 to 36 hours prior to ovulation.</li><ul> <li>(1) Stimulates luteinizing hormone (LH) release</li><ul> <li>Positive feedback</li> </ul><li>(2) Stimulates follicle-stimulating hormone (FSH) release</li><ul> <li>(a) Positive feedback on FSH and LH</li><li>(b) Serum LH > FSH; greatest positive feedback on LH
<blockquote style="color: blue; ">Ovulation: estrogen surge → LH surge → ovulation</blockquote></li> </ul><li>(3) LH surge initiates ovulation.</li> </ul> </ol><li>Ovulation</li><ol type="a"> <li>Occurs between days 14 and 16</li><li>Ovulation indicators</li><ul> <li>(1) Increase in body temperature</li><ul> <li>Effect of progesterone</li> </ul><li>(2) Subnuclear vacuoles in endometrial cells (<span>[[Fig. 21-11|Figure 21-11]]</span>)</li><li>(3) Mittelschmerz
<blockquote style="color: blue; ">Subnuclear vacuoles: sign of ovulation</blockquote></li><ul> <li>Peritoneal irritation from blood from the ruptured follicle</li> </ul> </ul> </ol><li>Secretory phase (see <span>[[Fig. 21-10|Figure 21-10]]</span>)</li><ol type="a"> <li>Progesterone-mediated</li><ul> <li><i>Least</i> variable phase of the cycle
<blockquote style="color: blue; ">Secretory phase: progesterone-mediated; least variable phase</blockquote></li> </ul><li>Increased gland tortuosity and secretion</li><li>Edema of stromal cells</li><li>Changes occurring after fertilization</li><ul> <li>(1) Fertilization usually occurs in the ampullary portion of the fallopian tube.</li><li>(2) Fertilized egg spends 3 days in the fallopian tube.</li><li>(3) Fertilized egg spends 2 days in the uterine cavity.
<blockquote style="color: blue; ">Arias-Stella phenomenon: exaggerated secretory phase that occurs in pregnancy</blockquote></li><ul> <li>Implants in the endometrial mucosa on day 21</li> </ul><li>(4) An exaggerated secretory phase occurs in pregnancy.</li><ul> <li>Called the Arias-Stella phenomenon</li> </ul> </ul> </ol><li>Menses</li><ol type="a"> <li>Initiated by drop-off in serum levels of estrogen and progesterone
<blockquote style="color: blue; ">Menses: drop in hormones initiates apoptosis</blockquote></li><ul> <li>(1) Signal for the endometrial cells to undergo apoptosis</li><li>(2) Newborn baby girls commonly have vaginal bleeding.</li><ul> <li>Due to sudden drop of maternal hormones with delivery
<blockquote style="color: blue; ">Newborn girls: may have vaginal bleeding</blockquote></li> </ul> </ul><li>Plasmin prevents menstrual blood from clotting.</li><ul> <li>Excess clotting is a sign of menorrhagia.</li> </ul> </ol><li>Functions of FSH</li><ol type="a"> <li>Prepares the follicle of the month</li><li>Increases aromatase synthesis in the granulosa cells
<blockquote style="color: blue; ">FSH: prepares follicle, aromatase synthesis, LH receptor synthesis</blockquote></li><li>Increases the synthesis of LH receptors</li> </ol><li>Functions of LH</li><ol type="a"> <li>LH in the proliferative phase</li><ul> <li>(1) Increases the synthesis of 17-ketosteroids (KS) in the theca interna (see <span>[[Fig. 21-9|Figure 21-9]]</span>)</li><ul> <li>17-KS are dehydroepiandrosterone (DHEA) and androstenedione.</li> </ul><li>(2) DHEA is converted to androstenedione.
<blockquote style="color: blue; ">LH proliferative phase: synthesize testosterone for conversion by aromatase into estradiol</blockquote></li><li>(3) An oxidoreductase converts androstenedione to testosterone.</li><li>(4) Testosterone enters granulosa cells and is aromatized to estradiol.</li> </ul><li>LH surge is induced by a sudden increase in estrogen.</li><ul> <li>Ovulation occurs when LH > FSH.</li> </ul><li>LH in the secretory phase (see <span>[[Fig. 21-9|Figure 21-9]]</span>)</li><ul> <li>Theca interna primarily synthesizes 17-hydroxyprogesterone (17-OH-progesterone).
<blockquote style="color: blue; ">LH secretory phase: synthesize 17-OH-progesterone</blockquote></li> </ul> </ol><li>Hormone changes in pregnancy</li><ol type="a"> <li>Human chorionic gonadotropin (hCG)
<blockquote style="color: blue; ">hCG: LH analogue</blockquote></li><ul> <li>(1) Synthesized in the syncytiotrophoblast lining the chorionic villus</li><li>(2) Acts as an LH analogue by maintaining the corpus luteum of pregnancy.
<blockquote style="color: blue; ">hCG: maintains corpus luteum of pregnancy for 8-10 weeks</blockquote></li><li>(3) Corpus luteum synthesizes progesterone for ∼8 to 10 weeks.</li> </ul><li>Corpus luteum involutes after ∼8 to 10 weeks.</li><ul> <li>(1) Placenta synthesizes progesterone for the remainder of the pregnancy.</li><li>(2) Spontaneous abortion may occur if placental production of progesterone is inadequate.</li> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC021020"></a> <br><a name="P021022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Mixture of estrogen + progestins (progesterone)</li><ol type="a"> <li>Baseline levels of estrogen prevent the midcycle estrogen surge.</li><ul> <li>Prevents the LH surge and ovulation
<blockquote style="color: blue; ">OCP: prevents LH surge and ovulation; progestins cause gland atrophy</blockquote></li> </ul><li>Progestins arrest the proliferative phase and cause gland atrophy.</li><li>Progestins inhibit LH, which also prevents the LH surge.</li> </ol><li>OCPs render the cervical mucus hostile to sperm.</li><li>OCPs alter fallopian tube motility.</li> </ol>
</div></html>
<html><a name="HC021021"></a> <br><a name="P021023"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Estradiol: estrogen of a nonpregnant woman</blockquote>
<ol type="1"> <li>Estradiol</li><ol type="a"> <li>Primary estrogen in nonpregnant women</li><li>Derived from aromatization of testosterone in granulosa cells</li> </ol><li>Estrone
<blockquote style="color: blue; ">Estrone: estrogen of a postmenopausal woman</blockquote></li><ol type="a"> <li>Weak estrogen produced during menopause</li><li>Derived from adipose cell aromatization of androstenedione</li><ul> <li>Androstenedione is synthesized in the adrenal cortex.
<blockquote style="color: blue; ">Estrone: androstenedione from adrenal converted by aromatase to estrone</blockquote></li> </ul> </ol><li>Estriol</li><ol type="a"> <li>End-product of estradiol metabolism</li><li>Primary estrogen of pregnancy</li><ul> <li>Derives from fetal adrenal, placenta, and maternal liver (refer section IX)
<blockquote style="color: blue; ">Estriol: estrogen of pregnancy</blockquote></li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021022"></a> <br><a name="P021024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Androstenedione</li><ul> <li>Equal derivation from ovaries and adrenal cortex</li> </ul><li>DHEA</li><ol type="a"> <li>Mainly synthesized in the adrenal cortex (80%)</li><li>Remainder is synthesized in the ovaries.</li> </ol><li>DHEA-sulfate
<blockquote style="color: blue; ">DHEA-sulfate: almost exclusively synthesized in adrenal cortex</blockquote></li><ul> <li>Almost exclusively synthesized in the adrenal cortex</li> </ul><li>Testosterone
<blockquote style="color: blue; ">Testosterone: ovary and adrenals</blockquote></li><ol type="a"> <li>Derived from conversion of androstenedione to testosterone</li><li>Testosterone is synthesized in the ovaries and adrenal glands.</li><ul> <li>Testosterone is peripherally converted to dehydroxytestosterone.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021023"></a><span>[[Fig. 21-12|Figure 21-12]]</span> <br> <br><a name="P021025"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">SHBG: synthesized in liver</blockquote>
<ol type="1"> <li>Binding protein for testosterone and estrogen (refer to <span macro="tag [[20 Lower Urinary Tract and Male Reproductive Disorders]] [[Chapter 20]]"></span>)</li><ol type="a"> <li>In both men and women, SHBG is primarily synthesized in the liver.</li><li>Estrogen increases synthesis of SHBG in the liver.</li><li>Androgens, obesity, hypothyroidism all decrease the synthesis of SHBG.
<blockquote style="color: blue; ">SHBG: higher binding affinity for testosterone than for estrogen</blockquote></li> </ol><li>SHBG has a greater binding affinity for testosterone than estrogen.</li><ol type="a"> <li>Increased SHBG decreases free testosterone (FT) levels.</li><li>Decreased SHBG increases FT levels.
<blockquote style="color: blue; ">SHBG: ↑ SHBG, ↓ FT; ↓ SHBG, ↑ FT</blockquote></li><ul> <li>Common cause of hirsutism in women (see later discussion)</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021024"></a> <br><a name="P021026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Plasma volume and RBC mass</li><ol type="a"> <li>Both are increased</li><ul> <li>Increase in plasma volume > increase in RBC mass.</li> </ul><li>Causes a 1-g/dL drop in hemoglobin (Hb) (dilutional effect)
<blockquote style="color: blue; ">Pregnancy: ↑ RBC mass/↑↑ plasma volume = ↓ Hb and RBC count (dilutional effect)</blockquote></li><li>Increases glomerular filtration rate (GFR)</li><ul> <li>(1) Creatinine clearance (CCr) is increased.</li><li>(2) Increased clearance of urea and creatinine</li><ul> <li>Serum levels are at the lower limit of normal.
<blockquote style="color: blue; ">Pregnancy: ↑↑ plasma volume causes ↑ GFR and CCr</blockquote></li> </ul><li>(3) Increases pressure to pump blood into the maternal lake in the placenta</li> </ul> </ol><li>Respiratory alkalosis</li><ol type="a"> <li>Effect of estrogen and progesterone stimulating respiratory center</li><li>Decrease in Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> causes a corresponding increase in Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>.
<blockquote style="color: blue; ">Pregnancy: respiratory alkalosis; estrogen/progesterone stimulation of respiratory center</blockquote></li> </ol><li>Increased serum thyroxine (T<sub>4</sub>) and cortisol</li><ol type="a"> <li>Estrogen stimulates synthesis of thyroid-binding globulin and transcortin.</li><li>Increased binding proteins increases total thyroxine and cortisol.</li><li>Metabolically active free hormone levels are normal (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>).</li><ul> <li><i>No</i> clinical signs of overactivity
<blockquote style="color: blue; ">Pregnancy: ↑ serum T<sub>4</sub>/cortisol; due to increase in binding proteins</blockquote></li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021025"></a> <br><a name="P021027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Defined as no menses for 1 year after age 40
<blockquote style="color: blue; ">Menopause: no menses for 1 year after age 40</blockquote></li><li>Causes</li><ul> <li>(1) Physiologic</li><ul> <li>(a) Waxing and waning of estrogen levels</li><ul> <li>Due to decreased ovarian function</li> </ul><li>(b) Depletion of granulosa and thecal cells</li><li>(c) Lack of response to gonadotropins</li><li>(d) Increased LH stimulates androgen production in stromal cells</li> </ul><li>(2) Surgical removal/radiation of ovaries</li><li>(3) Turner's syndrome (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><li>(4) Family history of early menopause</li><li>(5) Left-handedness</li> </ul><li>Average age of menopause is 51 years old.</li><ul> <li>(1) Age at which it occurs is genetically determined.</li><li>(2) Smokers reach menopause earlier than nonsmokers.</li><li>(3) Onset of perimenopause is mid- to late 40s</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Secondary amenorrhea</li><li>Hot flushes, night sweats
<blockquote style="color: blue; ">Menopause: hot flushes, night sweats, mood swings</blockquote></li><li>Atrophic vaginitis</li><ul> <li>Pruritus, burning, bleeding, dyspareunia</li> </ul><li>Mood swings, anxiety, depression, insomnia</li><li>Decreased libido</li><li>Urinary incontinence (refer to <span macro="tag [[20 Lower Urinary Tract and Male Reproductive Disorders]] [[Chapter 20]]"></span>)</li><li>Headaches, tiredness, lethargy</li><li>Osteoporosis (refer to <span macro="tag [[23 Musculoskeletal and Soft Tissue Disorders]] [[Chapter 23]]"></span>)</li><ul> <li>Increased risk for vertebral and Colles fractures</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Increase in FSH and LH
<blockquote style="color: blue; ">Menopause: ↑ FSH best marker; absence of menses for 12 months</blockquote></li><ul> <li>(1) Due to drop in estrogen and progesterone, respectively</li><li>(2) Serum FSH is the best marker.</li> </ul><li>Decreased serum estradiol</li><li>Serum FSH is the best marker.</li> </ol><li>Treatment</li><ol type="a"> <li>Estrogen replacement if symptomatic</li><li>Progestin added if uterus is still present</li><ul> <li>Prevent endometrial adenocarcinoma</li> </ul><li>Risks of long-term combined therapy</li><ul> <li>(1) Thromboembolism</li><li>(2) Coronary heart disease, stroke</li><li>(3) Slight risk for breast cancer</li><li>(4) Increased risk for dementia in women ≥ 65 years old</li><ul> <li>Applies also if only taking estrogen</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC021026"></a> <br><a name="P021028"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>Hirsutism is excess hair in normal hair-bearing areas (<span>[[Fig. 21-13|Figure 21-13]]</span>).</li><ul> <li>Virilization is hirsutism + male secondary sex characteristics.
<blockquote style="color: blue; ">Hirsutism: excess hair in normal hair-bearing areas</blockquote></li> </ul><li>Male secondary sex characteristics</li><ul> <li>(1) Increased muscle mass
<blockquote style="color: blue; ">Virilization: hirsutism + male secondary sex characteristics</blockquote></li><li>(2) Acne</li><li>(3) Enlarged clitoris (clitoromegaly) (<span>[[Fig. 21-14|Figure 21-14]]</span>)</li><ul> <li>Most important finding</li> </ul> </ul><li>Both conditions are due to increased androgens of ovarian or adrenal origin
<blockquote style="color: blue; ">Hirsutism and virilization: hyperandrogenicity of ovarian, adrenal, or drug origin</blockquote></li><ul> <li>(1) Ovarian origin-testosterone (free testosterone; sometimes total) is primarily increased</li><li>(2) Adrenal origin-DHEA-sulfate and testosterone increased</li> </ul><li>Causes</li><ul> <li>(1) Polycystic ovary syndrome (see later discussion; 75%)
<blockquote style="color: blue; ">Hirsutism: polycystic ovary syndrome most common cause</blockquote></li><li>(2) Idiopathic (5-15%)</li><li>(3) Adrenogenital syndrome (1-8%; refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li><li>(4) Insulin resistance syndrome (3-4%; see section VIII)</li><li>(5) Drugs (<1%)</li><ul> <li>Examples-androgenic progestins, phenytoin, cyclosporin, minoxidil</li> </ul><li>(6) Ovarian tumor (<1%; see section VIII)</li><ul> <li>Leydig cell tumor, Sertoli-Leydig cell tumor</li> </ul><li>(7) Adrenal tumor (<1%)</li><ul> <li>Adenoma/carcinoma producing Cushing's syndrome</li> </ul><li>(8) Obesity</li><ul> <li>Decreased SHBG causes an increase in free testosterone.</li> </ul><li>(9) Hypothyroidism</li> </ul> </ol><li>Polycystic ovary syndrome (POS)
<blockquote style="color: blue; ">Hirsutism, ovarian cause: ↑ testosterone</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Occurs in 3% of adolescents and adults
<blockquote style="color: blue; ">Hirsutism, adrenal cause: ↑ DHEA-S, testosterone</blockquote></li><li>(2) Symptoms begin around menarche.</li><li>(3) Increased risk of endometrial cancer</li><li>(4) Increased pituitary synthesis of LH and decreased synthesis of FSH
<blockquote style="color: blue; ">POS: increased risk for endometrial cancer</blockquote></li><ul> <li>(a) Increased LH increases androgen synthesis.</li><ul> <li>Hirsutism occurs more often than virilization.</li> </ul><li>(b) Androgens are aromatized to estrogen in the adipose cells.
<blockquote style="color: blue; ">POS: ↑ estrogen and androgens</blockquote></li><ul> <li>Increased estrogen increases risk for endometrial carcinoma.</li> </ul><li>(c) Increased estrogen has a positive feedback on LH and negative feedback on FSH.</li><li>(d) Suppression of FSH causes follicle degeneration.</li><li>(e) Fluid accumulation produces subcortical cysts that enlarge the ovaries (<span>[[Figs. 21-15|Figure 21-15]]</span> and <span>[[21-16|Figure 21-16]]</span>).</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Menstrual irregularities
<blockquote style="color: blue; ">POS: oligomenorrhea most common complaint</blockquote></li><ul> <li>Oligomenorrhea is the most common complaint.</li> </ul><li>(2) Hirsutism, infertility, obesity (40-50%)</li> </ul><li>Laboratory findings
<blockquote style="color: blue; ">POS: ↑ LH, ↓ FSH; LH:FSH ratio > 2</blockquote></li><ul> <li>(1) LH:FSH ratio > 2</li><li>(2) Increased serum testosterone (free and total) and androstenedione</li><li>(3) Increased serum estrogen</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Weight reduction in obese women</li><li>Low-dose OCPs or medroxyprogesterone
<blockquote style="color: blue; ">Rx of POS: low-dose OCPs or medroxyprogesterone</blockquote></li><ul> <li>Suppress ovarian steroidogenesis and LH</li> </ul><li>Spironolactone if OCPs unacceptable</li><ul> <li>Block androgen receptors on hair follicle</li> </ul><li>LH-releasing hormone analogues</li><ul> <li>Inhibit ovarian androgen production</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021027"></a> <br><a name="P021029"></a><div class="PA" style="color: black; "><ol type="1"> <li>Menorrhagia</li><ol type="a"> <li>Loss of blood > 80 mL per period
<blockquote style="color: blue; ">Menorrhagia: loss > 80 mL per period</blockquote></li><li>Menorrhagia likely if:</li><ul> <li>(1) Staining of sheets at night with heavy protection</li><li>(2) Excessive passage of clots</li><ul> <li>Indicates plasmin does <i>not</i> have enough time to dissolve clot</li> </ul> </ul> </ol><li>Dysmenorrhea</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Painful menses</li><li>(2) Approximately 50% of women have dysmenorrhea.</li><ul> <li>Approximately 10% are incapacitated for 1 to 3 days.</li> </ul><li>(3) Primary type</li><ul> <li>(a) Only occurs in ovulatory cycles
<blockquote style="color: blue; ">Primary dysmenorrhea: due to PGF<sub>2</sub><sub>α</sub>; increases uterine contractions</blockquote></li><li>(b) Due to increased prostaglandin F<sub>2</sub><sub>α</sub> (PGF<sub>2</sub><sub>α</sub>)</li><li>(c) Increases uterine contractions</li> </ul><li>(4) Secondary type
<blockquote style="color: blue; ">Secondary dysmenorrhea: endometriosis most common cause</blockquote></li><ul> <li>(a) Endometriosis (most common)</li><li>(b) Adenomyosis</li><li>(c) Leiomyomas</li><li>(d) Cervical stenosis</li> </ul> </ul><li>Treatment</li><ul> <li>(1) Primary type</li><ul> <li>Nonsteroidals; OCP; nifedipine; magnesium sulfate</li> </ul><li>(2) Secondary type</li><ul> <li>Treat the underlying disease</li> </ul> </ul> </ol><li>Dysfunctional uterine bleeding (DUB)</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Abnormal uterine bleeding <i>unrelated</i> to an anatomic cause
<blockquote style="color: blue; ">DUB: abnormal bleeding unrelated to an anatomic cause</blockquote></li><li>(2) Diagnosis of exclusion.</li><li>(3) Types of abnormal bleeding in DUB</li><ul> <li>(a) Menorrhagia</li><li>(b) Hypomenorrhea</li><ul> <li>Decreased amount of bleeding during normal cycle</li> </ul><li>(c) Metrorrhagia</li><ul> <li>Excessive flow and duration at irregular intervals</li> </ul><li>(d) Menometrorrhagia</li><ul> <li>Combination of menorrhagia and metrorrhagia</li> </ul><li>(e) Oligomenorrhea</li><ul> <li>Intervals > 35 days</li> </ul><li>(f) Polymenorrhea</li><ul> <li>Intervals < 21 days</li> </ul> </ul><li>(4) Most cases are postmenarchal and perimenopausal (most common).
<blockquote style="color: blue; ">DUB: occurs most often after menarche and in perimenopausal period</blockquote></li><ul> <li>Majority of these are anovulatory DUB.</li> </ul><li>(5) Overall, ∼90% of abnormal bleeding is caused by anovulation.</li><li>(6) During reproductive age, <10% of abnormal bleeding results from anovulation.</li> </ul><li>Anovulatory DUB</li><ul> <li>(1) Occurs at the extremes of reproductive life
<blockquote style="color: blue; ">Anovulatory DUB: most common type of DUB; excessive estrogen stimulation</blockquote></li><ul> <li>(a) Menarche to age 20 years</li><li>(b) Perimenopausal period</li> </ul><li>(2) Excessive estrogen stimulation relative to progesterone</li><ul> <li>(a) Absent secretory phase of the cycle</li><li>(b) Produces endometrial hyperplasia and excessive bleeding</li> </ul><li>(3) Treatment</li><ul> <li>OCPs; progestational agents</li> </ul> </ul><li>Inadequate luteal phase</li><ul> <li>(1) Ovulatory type of DUB
<blockquote style="color: blue; ">Ovulatory DUB: inadequate luteal phase; ↓ progesterone</blockquote></li><li>(2) Inadequate maturation of the corpus luteum</li><ul> <li>(a) Inadequate synthesis of progesterone</li><ul> <li>Delay in development of the secretory phase</li> </ul><li>(b) Decreased serum 17-hydroxyprogesterone</li><ul> <li>Blood drawn 7 days after ovulation: progesterone should be <14 pg/mL.</li> </ul><li>(c) Implicated in infertility and recurrent pregnancy loss</li> </ul><li>(3) Treatment</li><ul> <li>(a) If follicle size is normal (ultrasound), progesterone supplementation</li><li>(b) If follicle size is inadequate, clomiphene sulfate is recommended.</li> </ul> </ul><li>Irregular shedding of the endometrium</li><ul> <li>(1) Ovulatory type of DUB
<blockquote style="color: blue; ">Ovulatory DUB: irregular shedding of endometrium; persistent luteal phase</blockquote></li><li>(2) Persistent luteal phase with continued secretion of progesterone</li><li>(3) Mixture of proliferative and secretory glands in the menstrual effluent</li><li>(4) Treatment</li><ul> <li>OCP; medroxyprogesterone acetate</li> </ul> </ul> </ol><li>Causes of abnormal bleeding by age (<span>[[Table 21-2|Table 21-2. CAUSES OF ABNORMAL BLEEDING BY AGE]]</span>)</li> </ol>
</div></html>
<html><a name="HC021028"></a> <br><a name="P021030"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Primary amenorrhea</li><ul> <li>(1) Absence of menses by 16 years of age
<blockquote style="color: blue; ">Primary amenorrhea: most cases due to constitutional delay</blockquote></li><li>(2) Most cases are due to constitutional delay.</li><ul> <li>Family history of delayed onset of menses</li> </ul> </ul><li>Secondary amenorrhea</li><ul> <li>(1) Absence of menses for 3 months</li><li>(2) Most cases are due to pregnancy.
<blockquote style="color: blue; ">Secondary amenorrhea: most cases due to pregnancy</blockquote></li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Hypothalamic or pituitary disorder</li><ul> <li>(1) Decreased synthesis of FSH and LH</li><ul> <li>(a) Decreased synthesis of estrogen and progesterone</li><li>(b) Hypogonadotropic (↓ FSH and LH) hypogonadism</li> </ul><li>(2) <i>No</i> withdrawal bleeding after receiving progesterone</li><ul> <li>Endometrial mucosa is <i>not</i> estrogen-stimulated.
<blockquote style="color: blue; ">Hypothalamic/pituitary cause: ↓ FSH, LH, estrogen</blockquote></li> </ul><li>(3) Examples</li><ul> <li>(a) Hypopituitarism, prolactinoma (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li><li>(b) Anorexia nervosa (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>)</li> </ul> </ul><li>Ovarian disorder</li><ul> <li>(1) Decreased synthesis of estrogen and progesterone</li><ul> <li>(a) Increase in serum FSH and LH, respectively</li><li>(b) Hypergonadotropic (FSH and LH) hypogonadism
<blockquote style="color: blue; ">Ovarian cause: ↑ FSH, LH; ↓ estrogen</blockquote></li> </ul><li>(2) <i>No</i> withdrawal bleeding after receiving progesterone</li><ul> <li>Endometrial mucosa is <i>not</i> estrogen-stimulated.
<blockquote style="color: blue; ">Primary amenorrhea + poor female secondary sex characteristics: probable Turner's syndrome</blockquote></li> </ul><li>(3) Examples</li><ul> <li>(a) Turner's syndrome (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><li>(b) Surgical removal of ovaries</li> </ul> </ul><li>End-organ defect</li><ul> <li>(1) Prevents the normal egress of blood</li><ul> <li>More likely cause of primary amenorrhea</li> </ul><li>(2) Normal levels of FSH, LH, estrogen, and progesterone</li><li>(3) <i>No</i> withdrawal bleeding after receiving progesterone
<blockquote style="color: blue; ">End organ defect: normal FSH, LH, estrogen</blockquote></li><li>(4) Examples</li><ul> <li>(a) Imperforate hymen, Rokitansky-Kuster-Hauser syndrome</li><li>(b) Asherman syndrome
<blockquote style="color: blue; ">Asherman syndrome: removal of stratum basalis by curettage</blockquote></li><ul> <li>Removal of stratum basalis owing to repeated curettage</li> </ul> </ul> </ul><li>Summary of amenorrhea (<span>[[Table 21-3|Table 21-3. DIFFERENTIAL DIAGNOSIS OF AMENORRHEA]]</span>)</li> </ol> </ol>
</div></html>
![[21.V.A.Sequence to menarche]]
<<tiddler [[21.V.A.Sequence to menarche]]>>
![[21.V.B.Summary of the normal menstrual cycle]]
<<tiddler [[21.V.B.Summary of the normal menstrual cycle]]>>
![[21.V.C.Oral contraceptive pills (OCPs)]]
<<tiddler [[21.V.C.Oral contraceptive pills (OCPs)]]>>
![[21.V.D.Sources and types of estrogen]]
<<tiddler [[21.V.D.Sources and types of estrogen]]>>
![[21.V.E.Sources and types of androgens]]
<<tiddler [[21.V.E.Sources and types of androgens]]>>
![[21.V.F.Sex hormone-binding globulin (SHBG) (Fig. 21-12)]]
<<tiddler [[21.V.F.Sex hormone-binding globulin (SHBG) (Fig. 21-12)]]>>
![[21.V.G.Normal changes in pregnancy]]
<<tiddler [[21.V.G.Normal changes in pregnancy]]>>
![[21.V.H.Menopause]]
<<tiddler [[21.V.H.Menopause]]>>
![[21.V.I.Hirsutism and virilization]]
<<tiddler [[21.V.I.Hirsutism and virilization]]>>
![[21.V.J.Menstrual dysfunction]]
<<tiddler [[21.V.J.Menstrual dysfunction]]>>
![[21.V.K.Amenorrhea]]
<<tiddler [[21.V.K.Amenorrhea]]>>
<html><a name="HC021030"></a> <br><a name="P021041"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Uterine infection following delivery (vaginal/cesarean section) or abortion
<blockquote style="color: blue; ">Acute endometritis: uterine infection following delivery or abortion</blockquote></li><li>Rate of postpartum endometritis is 1% to 8%.</li><li>Most common genital tract infection following delivery</li><li>More common in preterm deliveries</li> </ol><li>Acute endometritis</li><ol type="a"> <li>Most often due to bacterial infection following delivery or miscarriage
<blockquote style="color: blue; ">Acute endometritis: group B streptococcus common pathogen</blockquote></li><li>Group B streptococcus <i>(Streptococcus agalactiae)</i> is a common pathogen.</li><li>Other pathogens-group A streptococcus, <i>Staphylococcus aureus, Bacteroides fragilis, C. trachomatis, N. gonorrhoeae, Escherichia coli</i></li><li>Clinical findings</li><ul> <li>(1) Fever</li><li>(2) Uterine tenderness</li><li>(3) Purulent or foul vaginal discharge (lochia)</li><li>(4) Abdominal pain</li> </ul><li>Treatment</li><ul> <li>Cefoxitin; ticarcillin-clavulanate; ampicillin-sulbactam</li> </ul> </ol><li>Chronic endometritis
<blockquote style="color: blue; ">Intrauterine device: <i>Actinomyces</i> infection</blockquote></li><ol type="a"> <li>Causes</li><ul> <li>(1) Retained placenta</li><li>(2) Gonorrhea, intrauterine device <i>(Actinomyces israelii)</i>
<blockquote style="color: blue; ">Chronic endometritis: presence of plasma cells in biopsy</blockquote></li> </ul><li>Key histologic finding is the presence of plasma cells.</li><li>Treatment (see earlier discussion)</li> </ol> </ol>
</div></html>
<html><a name="HC021031"></a> <br><a name="P021042"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Invagination of the stratum basalis into the myometrium (<span>[[Fig. 21-17|Figure 21-17]]</span>)</li><ul> <li>(1) Glands and stroma thicken myometrial tissue.
<blockquote style="color: blue; ">Adenomyosis: glands and stroma in myometrium</blockquote></li><li>(2) Produces uterine enlargement</li> </ul><li>Highest incidence in women in mid- to late 40s</li><li>Common finding in hysterectomy specimens</li> </ol><li>Clinical findings</li><ul> <li>Menorrhagia, dysmenorrhea, pelvic pain</li> </ul><li>Definitive diagnosis with myometrial biopsy</li><li>Treatment is hysterectomy.</li> </ol>
</div></html>
<html><a name="HC021032"></a> <br><a name="PB021003"></a><div class="BB" style="color: rgb(47, 79, 79); ">The <b>rectal pouch of Douglas</b> is anterior to the rectum and posterior to the uterus. It is the most dependent portion of the female pelvis. It can be palpated by digital rectal examination. It is a common site to collect blood (e.g., ruptured tubal pregnancy), malignant cells (e.g., seeding by ovarian cancer), endometrial implants, and pus (e.g., pelvic inflammatory disease).
<blockquote style="color: blue; ">Rectal pouch of Douglas: site for collection of blood, malignant cells, pus, endometrial implants</blockquote></div><a name="P021043"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Endometriosis: functioning glands and stroma outside the confines of the uterus</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Functioning glands and stroma are located <i>outside</i> the uterus (<span>[[Fig. 21-18|Figure 21-18]]</span>).</li><ul> <li>Cyclic bleeding of gland and stromal implants</li> </ul><li>Prevalence is highest in women with dysmenorrhea (40-60%)</li><li>Average age at time of diagnosis is 25 to 29 years old.</li><li>Multifactorial inheritance has been implicated.
<blockquote style="color: blue; ">Endometriosis: reverse menses most common cause; coelomic metaplasia; vascular/lymphatic spread</blockquote></li><ul> <li>Approximately 7% occurrence rate in first-degree female relatives</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Reverse menses through fallopian tubes (most common)</li><ul> <li>Implantation of viable endometrial cells</li> </ul><li>Coelomic metaplasia</li><li>Vascular or lymphatic spread
<blockquote style="color: blue; ">Endometriosis: ovaries most common site of implantation</blockquote></li> </ol><li>Common sites</li><ul> <li>Ovaries (most common), rectal pouch, fallopian tubes, intestine</li> </ul><li>Clinical findings</li><ol type="a"> <li>Dysmenorrhea (most common)</li><li>Abnormal bleeding</li><ul> <li>Premenstrual spotting, menorrhagia</li> </ul><li>Painful stooling during menses</li><ul> <li>Implants located in rectal pouch</li> </ul><li>Intestinal obstruction and bleeding during menses</li><li>Increased risk for ectopic pregnancy</li><li>Infertility, dyspareunia
<blockquote style="color: blue; ">Endometriosis triad: dysmenorrhea, dyspareunia, infertility</blockquote></li><li>Enlargement of ovaries</li><ul> <li>Blood-filled cysts</li> </ul> </ol><li>Diagnosis</li><ol type="a"> <li>Laparoscopy useful for diagnosis and treatment</li><ul> <li>Implants have a "powder burn" appearance
<blockquote style="color: blue; ">Endometriosis: laparoscopy useful for diagnosis and treatment</blockquote></li> </ul><li>Increased serum cancer antigen 125 (CA125)</li><ul> <li>(1) Excellent sensitivity but poor specificity (increased false positive results)</li><ul> <li>It is a cancer antigen that is also increased in surface derived ovarian cancers and other gynecologic disorders.</li> </ul><li>(2) More useful in excluding endometriosis when it returns negative</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Combination oral contraceptives</li><li>Progestins (e.g., medroxyprogesterone acetate)</li><li>Gonadotropin-releasing hormone agonists</li><li>Laparoscopic removal of implants</li> </ol> </ol>
</div></html>
<html><a name="HC021033"></a><span>[[Fig. 21-19|Figure 21-19]]</span> <br> <br><a name="P021044"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Benign polyp that enlarges with estrogen stimulation</li><li>Does <i>not</i> progress to endometrial carcinoma</li><li>Can protrude through the cervix into the vagina</li> </ol><li>Clinical findings
<blockquote style="color: blue; ">Endometrial polyp: common cause of menorrhagia; no risk for endometrial cancer</blockquote></li><ol type="a"> <li>Common cause of menorrhagia in 20- to 40-year-old age bracket</li><li>Spotting between menstrual periods or after menopause</li> </ol><li>Diagnosis</li><ol type="a"> <li>Vaginal ultrasound</li><li>Dilation and curettage (D&C)</li> </ol><li>Treatment</li><ol type="a"> <li>Dilation and curettage</li><li>Hysteroscopy</li> </ol> </ol>
</div></html>
<html><a name="HC021034"></a> <br><a name="P021045"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>Prolonged estrogen stimulation
<blockquote style="color: blue; ">Endometrial hyperplasia: prolonged estrogen stimulation</blockquote></li><li>Risk factors</li><ul> <li>(1) Early menarche or late menopause</li><li>(2) Nulliparity</li><li>(3) Obesity</li><ul> <li>Increased aromatization of androgens to estrogen</li> </ul><li>(4) Polycystic ovary syndrome</li><li>(5) Taking estrogen without progesterone</li><li>(6) Anovulatory menstrual cycles</li><li>(7) Hereditary nonpolyposis colon cancer (Lynch syndrome; refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>)</li> </ul><li>Classification</li><ul> <li>(1) Simple hyperplasia (<span>[[Fig. 21-20|Figure 21-20]]</span>)</li><ul> <li>(a) Increased number of cystically dilated glands</li><li>(b) <i>No</i> glandular crowding</li> </ul><li>(2) Complex hyperplasia</li><ul> <li>(a) Increased number of dilated glands with branching</li><li>(b) Glandular crowding
<blockquote style="color: blue; ">Endometrial hyperplasia: atypical hyperplasia greatest risk for endometrial cancer</blockquote></li> </ul><li>(3) Atypical hyperplasia</li><ul> <li>(a) Glandular crowding and dysplastic epithelium</li><li>(b) Greatest risk for endometrial cancer</li> </ul> </ul><li>High rate of spontaneous regression</li> </ol><li>Clinical findings</li><ol type="a"> <li>Menorrhagia, metrorrhagia, menometrorrhagia</li><li>Postmenopausal bleeding
<blockquote style="color: blue; ">Endometrial hyperplasia: postmenopausal bleeding</blockquote></li> </ol><li>Diagnosis</li><ul> <li>Endometrial biopsy</li> </ul><li>Treatment</li><ol type="a"> <li>OCPs</li><li>Medroxyprogesterone acetate</li><li>Hysterectomy if atypia is present</li> </ol> </ol>
</div></html>
<html><a name="HC021035"></a> <br><a name="P021046"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>Most common gynecologic tumor</li><li>Median age at onset, 60 years old
<blockquote style="color: blue; ">Endometrial carcinoma: most common gynecologic cancer; best prognosis</blockquote></li><li>Prolonged estrogen stimulation</li><ul> <li>Same risk factors as endometrial hyperplasia</li> </ul><li>OCPs decrease risk.</li><ul> <li>Due to antiestrogen effect of progestins
<blockquote style="color: blue; ">OCPs: ↓ risk for endometrial cancer</blockquote></li> </ul><li>Increased risk for breast cancer</li><li>Types of endometrial cancer</li><ul> <li>(1) Well-differentiated adenocarcinoma</li><ul> <li>(a) Most common type</li><li>(b) Adenoacanthoma</li><ul> <li>Contains foci of benign squamous tissue (no prognostic significance)</li> </ul><li>(c) Adenosquamous carcinoma</li><ul> <li>Contain foci of malignant squamous cancer (worse prognosis)</li> </ul> </ul><li>(2) Papillary adenocarcinoma</li><ul> <li>Highly aggressive cancer</li> </ul> </ul> </ol><li>Cancer characteristics</li><ol type="a"> <li>Spreads down into the endocervix</li><li>Spreads out into the uterine wall (<span>[[Fig. 21-21|Figure 21-21]]</span>)</li><li>Lungs are the most common site of metastasis</li> </ol><li>Clinical findings</li><ul> <li>Postmenopausal bleeding (90%)
<blockquote style="color: blue; ">Endometrial cancer: postmenopausal bleeding most common finding</blockquote></li> </ul><li>Diagnosis</li><ul> <li>Endometrial biopsy</li> </ul><li>Treatment</li><ul> <li>Surgery, radiation, hormones (tamoxifen), or chemotherapy depending on stage</li> </ul> </ol>
</div></html>
<html><a name="HC021036"></a> <br><a name="P021047"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Benign smooth muscle tumor (<span>[[Fig. 21-22|Figure 21-22]]</span>)
<blockquote style="color: blue; ">Leiomyoma: most common benign connective tissue tumor in women</blockquote></li><li>Most frequently diagnosed gynecologic tumor</li><li>Occurs in 20% to 50% of women > 30 years old</li><li>More common in blacks than whites</li><li>Estrogen-sensitive tumors</li><ul> <li>May become larger during pregnancy</li> </ul> </ol><li>Tumor characteristics</li><ol type="a"> <li>Commonly undergo the following:</li><ul> <li>(1) Degeneration</li><li>(2) Dystrophic calcification</li><li>(3) Hyalinization</li><ul> <li>Reason for the term "fibroids"</li> </ul> </ul><li>They rarely transform into leiomyosarcomas (<1%).</li> </ol><li>Clinical findings</li><ol type="a"> <li>Menorrhagia (when located in submucosa)</li><li>Obstructive delivery
<blockquote style="color: blue; ">Clinical: menorrhagia; obstructive delivery</blockquote></li><li>Cramping during menses</li><li>Pressure on colon (constipation)</li><li>Pressure on bladder</li><ul> <li>Increased frequency, urgency, incontinence</li> </ul> </ol><li>Diagnosis</li><ol type="a"> <li>Transabdominal or transvaginal ultrasound</li><li>MRI</li> </ol><li>Treatment</li><ol type="a"> <li>Myotomy if women want to preserve fertility</li><li>Hysterectomy</li> </ol> </ol>
</div></html>
<html><a name="HC021037"></a> <br><a name="P021048"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common sarcoma of the uterus
<blockquote style="color: blue; ">Leiomyosarcoma: most common sarcoma of uterus</blockquote></li><li>Tumor characteristics</li><ul> <li>Numerous atypical mitoses and foci of necrosis</li> </ul><li>Treatment is surgery.</li> </ol>
</div></html>
<html><a name="HC021038"></a> <br><a name="P021049"></a><div class="PA" style="color: black; "><ol type="1"> <li>Endometrial adenocarcinoma + malignant mesenchymal (stromal) tumor</li><ol type="a"> <li>Primarily occur in postmenopausal women</li><li>Bulky, necrotic tumors that often protrude through the cervical os</li> </ol><li>Mesenchymal component may include muscle, cartilage, and bone.
<blockquote style="color: blue; ">Carcinosarcoma: association with previous irradiation</blockquote></li><li>Strong association with previous irradiation</li><li>Poor prognosis</li><li>Treatment is surgery.</li> </ol>
</div></html>
![[21.VI.A.Endometritis]]
<<tiddler [[21.VI.A.Endometritis]]>>
![[21.VI.B.Adenomyosis]]
<<tiddler [[21.VI.B.Adenomyosis]]>>
![[21.VI.C.Endometriosis]]
<<tiddler [[21.VI.C.Endometriosis]]>>
![[21.VI.D.Endometrial polyp (Fig. 21-19)]]
<<tiddler [[21.VI.D.Endometrial polyp (Fig. 21-19)]]>>
![[21.VI.E.Endometrial hyperplasia]]
<<tiddler [[21.VI.E.Endometrial hyperplasia]]>>
![[21.VI.F.Endometrial carcinoma]]
<<tiddler [[21.VI.F.Endometrial carcinoma]]>>
![[21.VI.G.Leiomyoma ("fibroids")]]
<<tiddler [[21.VI.G.Leiomyoma ("fibroids")]]>>
![[21.VI.H.Leiomyosarcoma]]
<<tiddler [[21.VI.H.Leiomyosarcoma]]>>
![[21.VI.I.Malignant mixed müllerian tumors (carcinosarcomas)]]
<<tiddler [[21.VI.I.Malignant mixed müllerian tumors (carcinosarcomas)]]>>
<html><a name="HC021040"></a> <br><a name="P021056"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Hydatid cysts: cystic müllerian remnant; may undergo torsion</blockquote>
<ol type="1"> <li>Cystic müllerian remnants</li><li>Most often located around the fimbriated end of the tube</li><li>May undergo torsion (>25%), causing abdominal pain</li><li>Treatment is surgical removal (laparoscope).</li> </ol>
</div></html>
<html><a name="HC021041"></a> <br><a name="P021057"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Diagnosed in 2% to 5% of women in STD clinics</li><li>Most common cause of female infertility and ectopic pregnancy
<blockquote style="color: blue; ">PID: most common cause of female infertility and ectopic pregnancy</blockquote></li><li>Risk factors</li><ul> <li>(1) Multiple sexual partners</li><li>(2) Vaginal douching</li><li>(3) Previous episodes of PID</li><li>(4) Unprotected sex</li> </ul><li>Most but not all cases of PID are STDs.</li><li>Causes of PID</li><ul> <li>(1) Most often due to <i>N. gonorrhoeae</i> or <i>C. trachomatis</i></li><ul> <li>Coexisting infection in 45% of cases</li> </ul><li>(2) Other pathogens (<i>not</i> STD)
<blockquote style="color: blue; ">PID: most common cause is <i>N. gonorrhoeae</i> and <i>C. trachomatis</i>; both present in 45% of cases</blockquote></li><ul> <li><i>B. fragilis</i>, streptococci, <i>Clostridium perfringens, Mycobacteria tuberculosis</i>, cytomegalovirus (CMV)</li> </ul> </ul> </ol><li>Gross findings</li><ol type="a"> <li>Fallopian tubes are filled with pus (<span>[[Fig. 21-23|Figure 21-23]]</span>).</li><li>Most common cause of hydrosalpinx</li><ul> <li>Pus resorbs, leaving a clear fluid distending the tube.</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Fever usually >38.3°C (101°F)</li><li>Lower abdominal pain
<blockquote style="color: blue; ">PID: cervical motion, adnexal, uterine tenderness highly predictive of PID</blockquote></li><li>Cervical motion, adnexal, uterine tenderness on pelvic examination</li><li>Abnormal uterine bleeding; vaginal discharge</li><li>Mucopurulent discharge in cervical os</li><li>Right upper quadrant pain (5%)</li><ul> <li>Perihepatitis (Fitz-Hughes-Curtis syndrome; see <span>[[Table 21-1|Table 21-1. SEXUALLY TRANSMITTED DISEASES AND OTHER GENITAL INFECTIONS]]</span>)</li> </ul> </ol><li>Diagnosis</li><ol type="a"> <li>Finding of cervical motion tenderness and adnexal tenderness</li><li>Culture of cervical discharge</li><li>Laparoscopy</li><li>Transvaginal ultrasound; MRI (best sensitivity and specificity)
<blockquote style="color: blue; ">Rx PID: ceftriaxone (for <i>N. gonorrhoeae</i>) + doxycycline (for <i>C. trachomatis</i>)</blockquote></li> </ol><li>Treatment</li><ol type="a"> <li>Empiric treatment with uterine, adnexal, and cervical motion tenderness</li><li>Ceftriaxone + doxycycline (covers both <i>N. gonorrhoeae</i> and <i>C. trachomatis</i>)</li> </ol> </ol>
</div></html>
<html><a name="HC021042"></a> <br><a name="P021058"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">SIN: tubal diverticulosis</blockquote>
<ol type="1"> <li>Invagination of the mucosa into the muscle ("tubal diverticulosis")</li><ol type="a"> <li>Produces nodules in the tube that narrow the lumen</li><li>Probably a postinfectious reaction (e.g., previous <i>C. trachomatis</i> infection)</li> </ol><li>Complications</li><ul> <li>Infertility, ectopic pregnancy</li> </ul><li>Diagnose with hysterosalpingography</li><ul> <li>Beading appearance in areas of constriction</li> </ul> </ol>
</div></html>
<html><a name="HC021043"></a> <br><a name="P021059"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>Implantation of a fetus outside the normal uterine location</li><li>Occurs in 1% to 2% of pregnancies</li><li>Accounts for 13% of maternal deaths</li><li>Risk factors</li><ul> <li>(1) Scarring from previous PID (most common cause)
<blockquote style="color: blue; ">EP: most common cause is previous PID</blockquote></li><li>(2) Endometriosis</li><li>(3) Altered tubal motility, SIN</li><li>(4) Progestin-only pill; previous tubal ligation</li> </ul><li>Sites of implantation</li><ul> <li>(1) Majority occur within the tubes (<span>[[Fig. 21-24|Figure 21-24]]</span>)</li><ul> <li>Most are in the broad ampullary portion below the fimbriae.</li> </ul><li>(2) Ovaries, abdominal cavity</li> </ul> </ol><li>Clinical findings
<blockquote style="color: blue; ">EP: classic triad-vaginal bleeding, pelvic pain, adnexal mass</blockquote></li><ol type="a"> <li>Sudden onset of lower abdominal pain and tenderness (95%)</li><ul> <li>Usually ∼6 weeks after a previous normal menstrual period</li> </ul><li>Adnexal tenderness (87-99%)</li><li>Peritoneal signs (rebound tenderness; >70%)</li><li>Abnormal uterine bleeding (75%)</li><li>Hypovolemic shock (intraperitoneal bleeding; 2-17%)</li> </ol><li>Complications</li><ol type="a"> <li>Rupture with intra-abdominal bleed
<blockquote style="color: blue; ">EP: most common cause of death in early pregnancy</blockquote></li><ul> <li>Most common cause of death in early pregnancy</li> </ul><li>Most common cause of hematosalpinx</li><ul> <li>Blood in the tube</li> </ul> </ol><li>Diagnosis
<blockquote style="color: blue; ">EP: most common cause of hematosalpinx</blockquote></li><ol type="a"> <li>β-hCG is the best screening test.</li><ul> <li>(1) Urine screen is usually sensitive enough.</li><li>(2) Serum test is used if the urine screen is negative.</li><li>(3) Positive test does <i>not</i> prove that an ectopic pregnancy is present.</li> </ul><li>Vaginal ultrasound is the confirmatory test.</li><ul> <li>Check for an amniotic sac.</li> </ul><li>Laparoscopy is used in equivocal cases.</li> </ol><li>Treatment</li><ol type="a"> <li>Methotrexate if stable and no hemorrhage</li><li>Conservative surgery; salpingectomy</li> </ol> </ol>
</div></html>
![[21.VII.A.Hydatid cysts of Morgagni]]
<<tiddler [[21.VII.A.Hydatid cysts of Morgagni]]>>
![[21.VII.B.Pelvic inflammatory disease (PID)]]
<<tiddler [[21.VII.B.Pelvic inflammatory disease (PID)]]>>
![[21.VII.C.Salpingitis isthmica nodosa (SIN)]]
<<tiddler [[21.VII.C.Salpingitis isthmica nodosa (SIN)]]>>
![[21.VII.D.Ectopic pregnancy (EP)]]
<<tiddler [[21.VII.D.Ectopic pregnancy (EP)]]>>
<html><a name="HC021045"></a> <br><a name="P021062"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common ovarian mass
<blockquote style="color: blue; ">Follicular cyst: most common ovarian mass; non-neoplastic</blockquote></li><li>Non-neoplastic cyst</li><ul> <li>Accumulation of fluid in a follicle or previously ruptured follicle</li> </ul><li>Rupture produces sterile peritonitis with pain.</li><li>Most regress spontaneously.</li><li>Ultrasound is the best screening test.</li><li>Surgical removal if symptomatic</li> </ol>
</div></html>
<html><a name="HC021046"></a> <br><a name="P021063"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common ovarian mass in pregnancy
<blockquote style="color: blue; ">Corpus luteum cyst: most common ovarian mass in pregnancy; non-neoplastic</blockquote></li><li>Non-neoplastic cyst</li><ol type="a"> <li>Accumulation of fluid in the corpus luteum during pregnancy</li><li>May be confused with an amniotic sac</li><li>Most regress spontaneously.</li> </ol><li>Surgical removal if symptomatic</li> </ol>
</div></html>
<html><a name="HC021047"></a> <br><a name="P021064"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Oophoritis: complication of mumps or PID</blockquote>
<ul> <li>May be a complication of mumps or pelvic inflammatory disease</li> </ul>
</div></html>
<html><a name="HC021048"></a> <br><a name="P021065"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Occurs primarily in obese postmenopausal women</li><ul> <li>Causes bilateral ovarian enlargement</li> </ul><li>Hypercellular ovarian stroma</li><ul> <li>(1) Vacuolated (luteinized) stromal hilar cells are present</li><ul> <li>Synthesize excess androgens</li> </ul><li>(2) May cause hirsutism or virilization</li> </ul> </ol><li>Clinical findings
<blockquote style="color: blue; ">Stromal hyperthecosis: hirsutism/virilization, hypertension, insulin resistance (metabolic syndrome)</blockquote></li><ol type="a"> <li>Hirsutism or virilization</li><li>Association with acanthosis nigricans and insulin resistance</li><li>Hypertension</li> </ol><li>Treatment is oophorectomy.</li> </ol>
</div></html>
<html><a name="HC021049"></a> <br><a name="P021066"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>Tumors are more likely benign in women < 45 years of age.</li><ul> <li>(1) Risk increases with age.</li><li>(2) Median age of presentation is 61 years of age.</li><li>(3) Peaks in the late 70s</li><li>(4) Approximately 60% present with advanced disease.
<blockquote style="color: blue; ">Ovarian cancer: risk increases with age</blockquote></li> </ul><li>Risk factors</li><ul> <li>(1) Nulliparity</li><ul> <li>(a) Increased number of ovulatory cycles increases risk.</li><li>(b) Increased risk for surface-derived ovarian tumors
<blockquote style="color: blue; ">Ovarian cancer: genetic factors; excess estrogen exposure</blockquote></li> </ul><li>(2) Genetic factors</li><ul> <li>(a) Mutations of <i>BRCA1</i> and <i>BRCA2</i> suppressor genes</li><li>(b) Lynch syndrome (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>)</li><li>(c) Turner's syndrome (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><ul> <li>Increased risk for dysgerminoma</li> </ul><li>(d) Peutz-Jeghers syndrome (refer to <span macro="tag [[17 Gastrointestinal Disorders]] [[Chapter 17]]"></span>)</li><ul> <li>Increased incidence of sex cord tumors with annular tubules</li> </ul> </ul><li>(3) History of breast cancer
<blockquote style="color: blue; ">OCPs/pregnancy: ↓ risk for surface-derived ovarian cancers</blockquote></li><li>(4) Postmenopausal estrogen therapy; obesity (increased estrogen)</li><li>(5) OCPs/pregnancy decrease risk for surface-derived ovarian cancers.</li><ul> <li>Decreased number of ovulatory cycles
<blockquote style="color: blue; ">Surface-derived tumors: most common group of ovarian tumors</blockquote></li> </ul> </ul> </ol><li>Classification of ovarian tumors (<span>[[Table 21-4|Table 21-4. CLASSIFICATION OF OVARIAN TUMORS]]</span> and <span>[[Fig. 21-25|Figure 21-25]]</span>)</li><ol type="a"> <li>Surface-derived tumors</li><ul> <li>(1) Account for 65% to 70% of ovarian tumors</li><li>(2) Derive from coelomic epithelium</li><li>(3) Account for the greatest number of malignant ovarian tumors</li><li>(4) Malignant tumors commonly seed the omentum (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>).</li> </ul><li>Germ cell tumors
<blockquote style="color: blue; ">Malignant surface-derived cancers: commonly seed the abdominal cavity</blockquote></li><ul> <li>(1) Account for 15% to 20% of ovarian tumors</li><li>(2) Cancers are similar to those seen in the testicle (refer to <span macro="tag [[20 Lower Urinary Tract and Male Reproductive Disorders]] [[Chapter 20]]"></span>).</li><li>(3) A relatively small number of tumors are malignant.</li> </ul><li>Sex cord stromal tumors
<blockquote style="color: blue; ">Germ cell tumors: teratoma and dysgerminoma most common benign and malignant, respectively</blockquote></li><ul> <li>(1) Account for 3% to 5% of ovarian tumors</li><li>(2) Derive from stromal cells</li><li>(3) May be hormone-producing</li><li>(4) Majority of tumors are benign.
<blockquote style="color: blue; ">Sex cord stromal tumors: hormone producing tumors; most are benign</blockquote></li> </ul><li>Metastasis</li><ul> <li>(1) Accounts for 5% of ovarian tumors</li><li>(2) Common primary cancers metastasizing to ovaries</li><ul> <li>Breast, stomach (e.g., Krukenberg tumors)</li> </ul> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Abdominal enlargement due to fluid (most common sign)
<blockquote style="color: blue; ">Ovarian cancer: abdominal enlargement due to fluid most common sign</blockquote></li><ul> <li>(1) Malignant ascites most often due to seeding</li><li>(2) Signs of malignant ascites due to seeding
<blockquote style="color: blue; ">Serous cystadenocarcinoma: most common ovarian cancer; bilaterality; psammoma bodies</blockquote></li><ul> <li>(a) Induration in the rectal pouch on digital rectal examination</li><li>(b) Intestinal obstruction with colicky pain
<blockquote style="color: blue; ">Ovarian cancer: palpable ovaries in postmenopausal women is cancer until proved otherwise</blockquote></li> </ul> </ul><li>Palpable ovarian mass in a postmenopausal woman</li><ul> <li>Ovaries should <i>not</i> be palpable in menopausal women.</li> </ul><li>Malignant pleural effusion</li><ul> <li>Common site for ovarian cancer metastasis</li> </ul><li>Cystic teratomas undergo torsion leading to infarction.</li><ul> <li>Radiographs show calcification from bone or teeth (see <span>[[Fig. 8-3|Figure 8-3]]</span>).
<blockquote style="color: blue; ">Sex cord stromal tumors: ↑ estrogen/androgens</blockquote></li> </ul><li>Signs of hyperestrinism from estrogen-secreting tumors</li><ul> <li>(1) Bleeding from endometrial hyperplasia/cancer</li><li>(2) 100% superficial squamous cells in a cervical Pap smear</li> </ul><li>Hirsutism or virilization from androgen-secreting tumors</li> </ol><li>Tumor markers</li><ol type="a"> <li>Increased serum cancer antigen 125 (CA125)</li><li>Only increased in surface-derived malignant tumors
<blockquote style="color: blue; ">Surface-derived tumors: ↑ CA125</blockquote></li> </ol><li>Treatment</li><ul> <li>Surgery, chemotherapy, occasionally radiation</li> </ul><li>Prognosis</li><ol type="a"> <li>Better prognosis if <65 years old</li><li>Overall 1- and 5-year relative survival rates for ovarian cancer are 75% and 45%, respectively.</li> </ol> </ol>
</div></html>
![[21.VIII.A.Follicular cyst]]
<<tiddler [[21.VIII.A.Follicular cyst]]>>
![[21.VIII.B.Corpus luteum cyst]]
<<tiddler [[21.VIII.B.Corpus luteum cyst]]>>
![[21.VIII.C.Oophoritis]]
<<tiddler [[21.VIII.C.Oophoritis]]>>
![[21.VIII.D.Stromal hyperthecosis]]
<<tiddler [[21.VIII.D.Stromal hyperthecosis]]>>
![[21.VIII.E.Ovarian tumors]]
<<tiddler [[21.VIII.E.Ovarian tumors]]>>
<html><a name="HC021059"></a> <br><a name="P021082"></a><div class="PA" style="color: black; "><ol type="1"> <li>High-density locations of breast tissue</li><ol type="a"> <li>Upper outer quadrant
<blockquote style="color: blue; ">Upper outer quadrant: most common location for cancer</blockquote></li><ul> <li>Underscores why cancer is most commonly located in this quadrant</li> </ul><li>Beneath the nipple</li> </ol><li>Hormone effects during menstrual cycle</li><ol type="a"> <li>Estrogen</li><ul> <li>Stimulates ductal and alveolar growth</li> </ul><li>Progesterone</li><ul> <li>Stimulates alveolar differentiation</li> </ul> </ol><li>Hormone effects in lactation</li><ol type="a"> <li>Prolactin</li><ul> <li>Stimulates and maintains lactogenesis</li> </ul><li>Oxytocin</li><ul> <li>(1) Released by suckling reflex</li><li>(2) Expulsion of milk into ducts</li> </ul> </ol><li>Lymph nodes</li><ol type="a"> <li>Outer quadrant cancers
<blockquote style="color: blue; ">Outer quadrant cancer: axillary node involvement</blockquote></li><ul> <li>Drain to the axillary lymph nodes
<blockquote style="color: blue; ">Inner quadrant cancer: internal mammary node involvement</blockquote></li> </ul><li>Inner quadrant cancers</li><ul> <li>Drain to the internal mammary nodes</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021060"></a><span>[[Fig. 21-33|Figure 21-33]]</span> <br> <br> </html>
![[21.X.A.Clinical anatomy]]
<<tiddler [[21.X.A.Clinical anatomy]]>>
![[21.X.B.Locations for breast lesions (Fig. 21-33)]]
<<tiddler [[21.X.B.Locations for breast lesions (Fig. 21-33)]]>>
![[21.X.C.Nipple discharges]]
<<tiddler [[21.X.C.Nipple discharges]]>>
![[21.X.D.Breast pain]]
<<tiddler [[21.X.D.Breast pain]]>>
![[21.X.E.Fibrocystic change (FCC)]]
<<tiddler [[21.X.E.Fibrocystic change (FCC)]]>>
![[21.X.F.Inflammation]]
<<tiddler [[21.X.F.Inflammation]]>>
![[21.X.G.Benign breast tumors]]
<<tiddler [[21.X.G.Benign breast tumors]]>>
![[21.X.H.Breast cancer]]
<<tiddler [[21.X.H.Breast cancer]]>>
![[21.X.I.Gynecomastia]]
<<tiddler [[21.X.I.Gynecomastia]]>>
![[21.X.J.Breast cancer in men]]
<<tiddler [[21.X.J.Breast cancer in men]]>>
<html><a name="HC021061"></a> <br><a name="P021083"></a><div class="PA" style="color: black; "><ol type="1"> <li>Galactorrhea; causes other than lactation:
<blockquote style="color: blue; ">Galactorrhea: mechanical stimulation of nipple most common physiologic cause</blockquote></li><ol type="a"> <li>Mechanical stimulation of the nipple</li><ul> <li>(1) Prolonged sucking of nipple</li><li>(2) Sexual intercourse</li><li>(3) Most common physiologic cause of galactorrhea
<blockquote style="color: blue; ">Prolactinoma: most common pathologic cause of galactorrhea</blockquote></li> </ul><li>Prolactinoma (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li><ul> <li>Most common pathologic cause of galactorrhea (<span>[[Fig. 21-34|Figure 21-34]]</span>)</li> </ul><li>Primary hypothyroidism (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li><ul> <li>(1) Most common nonpituitary endocrine disease causing galactorrhea
<blockquote style="color: blue; ">Galactorrhea: primary hypothyroidism; ↑ TRH stimulates prolactin release</blockquote></li><li>(2) Decreased serum thyroxine increases thyrotropin-releasing factor (TRF).</li><ul> <li>TRF stimulates prolactin.</li> </ul> </ul><li>Drugs
<blockquote style="color: blue; ">Galactorrhea: drugs very common cause</blockquote></li><ul> <li>Examples-OCPs, phenothiazines, methyldopa, H<sub>2</sub>-receptor blockers, anxiolytics</li> </ul> </ol><li>Bloody nipple discharge
<blockquote style="color: blue; ">Bloody discharge: intraductal papilloma; ductal cancer</blockquote></li><ul> <li>Intraductal papilloma, ductal cancer</li> </ul><li>Purulent nipple discharge</li><ol type="a"> <li>Acute mastitis due to <i>Staphylococcus aureus</i></li><li>Usually occurs during lactation or breast-feeding</li><li>Treatment</li><ul> <li>(1) If not methicillin resistant, dicloxacillin or cephalexin</li><li>(2) If methicillin resistant, trimethoprim-sulfamethoxazole
<blockquote style="color: blue; ">Purulent discharge: acute mastitis during breast feeding</blockquote></li> </ul> </ol><li>Greenish brown nipple discharge</li><ul> <li>Mammary duct ectasia (plasma cell mastitis)</li> </ul> </ol>
</div></html>
<html><a name="HC021062"></a> <br><a name="P021084"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common cause is fibrocystic change
<blockquote style="color: blue; ">Breast pain: most common cause is fibrocystic change</blockquote></li><li>Mondor's disease</li><ol type="a"> <li>Superficial thrombophlebitis of veins overlying the breast</li><li>Presents as a palpable, painful cord</li> </ol> </ol>
</div></html>
<html><a name="HC021063"></a> <br><a name="P021085"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology and pathogenesis</li><ol type="a"> <li>Most common painful breast mass in women < 50 years old
<blockquote style="color: blue; ">FCC: most common breast mass in women < 50 years old</blockquote></li><li>Occurs in >50% of women in the reproductive period of life</li><li>Distortion of normal cyclic breast changes</li> </ol><li>Small and large cysts (<span>[[Fig. 21-35|Figure 21-35]]</span>)
<blockquote style="color: blue; ">Cysts and fibrosis: "lumpy bumpy" feeling on breast examination</blockquote></li><ol type="a"> <li>Some cysts have hemorrhage into the cyst fluid.</li><ul> <li>Called "blue-domed" cysts</li> </ul><li>Vary in size with the menstrual cycle</li><li><i>No</i> malignant potential</li><li>May have to surgically remove if recurrent</li> </ol><li>Fibrosis</li><ul> <li><i>No</i> malignant potential</li> </ul><li>Sclerosing adenosis</li><ol type="a"> <li>Proliferation of small ductules/acini in the lobule</li><ul> <li>Pattern is often confused with infiltrating ductal cancer.
<blockquote style="color: blue; ">Sclerosing adenosis: often contain microcalcifications seen on mammogram</blockquote></li> </ul><li>Often contain microcalcifications</li> </ol><li>Ductal hyperplasia</li><ol type="a"> <li>Ducts are estrogen-sensitive.</li><li>Pathologic findings</li><ul> <li>(1) Papillary proliferation is called papillomatosis.</li><li>(2) Apocrine metaplasia refers to the presence of large, pink-staining cells.
<blockquote style="color: blue; ">Atypical ductal hyperplasia: increased risk for breast cancer</blockquote></li><li>(3) Atypical ductal hyperplasia</li><ul> <li>Increased risk for developing cancer, because it is due to excess estrogen stimulation</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC021064"></a> <br><a name="P021086"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acute mastitis (see earlier discussion)</li><li>Mammary duct ectasia (plasma cell mastitis)</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Affects 25% of women in menopause</li><li>(2) Main ducts fill up with debris.
<blockquote style="color: blue; ">Mammary duct ectasia: common in menopause; greenish brown nipple discharge</blockquote></li><ul> <li>(a) Causes dilation, rupture, and inflammation</li><li>(b) Greenish brown nipple discharge</li> </ul><li>(3) May produce skin and nipple retraction simulating cancer</li><li>(4) <i>No</i> increased risk for breast cancer</li> </ul><li>Treatment</li><ul> <li>(1) Antibiotics if infection is present</li><li>(2) Surgical removal of blocked duct</li> </ul> </ol><li>Traumatic fat necrosis</li><ol type="a"> <li>Trauma to breast tissue</li><li>Microscopic findings</li><ul> <li>(1) Lipid-laden macrophages with foreign body giant cells</li><li>(2) Fibrosis, dystrophic calcification
<blockquote style="color: blue; ">Traumatic fat necrosis: usually painless indurated mass; associated with trauma to breast tissue</blockquote></li> </ul><li>Painless, indurated mass</li><ul> <li>Painful in acute stage</li> </ul><li>May produce skin retraction simulating cancer</li> </ol><li>Silicone breast implant</li><ol type="a"> <li>Polymer of silica, oxygen, and hydrogen</li><li>Silicone gel can leak or the implant can rupture
<blockquote style="color: blue; ">Silicone breast implant rupture: foreign body giant cell reaction</blockquote></li><ul> <li>(1) Produces foreign body giant cells and chronic inflammation</li><li>(2) Association with autoimmune disease is <i>not</i> proved.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021065"></a> <br><a name="P021087"></a><div class="PA" style="color: black; "><ol type="1"> <li>Fibroadenoma</li><ol type="a"> <li>Epidemiology
<blockquote style="color: blue; ">Fibroadenoma: most common breast tumor women < 40 years old</blockquote></li><ul> <li>(1) Most common breast tumor in women < 35 years old</li><li>(2) Most commonly diagnosed breast tumor</li><li>(3) Develop in 50% of women who receive cyclosporine after renal transplantation</li><li>(4) Discrete movable, painless or painful mass (<span>[[Fig. 21-36|Figure 21-36]]</span>).</li><ul> <li>Multiple lesions may be present (10-15%).
<blockquote style="color: blue; ">Fibroadenoma: commonly develop in women taking cyclosporine</blockquote></li> </ul><li>(5) Benign tumor derived from the stroma</li><ul> <li>(a) Stroma proliferates and compresses the ducts (<span>[[Fig. 21-37|Figure 21-37]]</span>).</li><li>(b) Duct epithelium is <i>not</i> neoplastic.
<blockquote style="color: blue; ">Fibroadenoma: benign tumor derived from stroma</blockquote></li> </ul><li>(6) Increases in size during pregnancy</li><ul> <li>Estrogen-sensitive</li> </ul><li>(7) May spontaneously disappear or involute during menopause</li><li>(8) Do <i>not</i> progress into cancer; however, breast cancer may secondarily develop within duct epithelial cells as a separate event (3%)</li> </ul><li>Diagnosis</li><ul> <li>Fine needle or core needle biopsy</li> </ul><li>Treatment</li><ul> <li>(1) Surgical removal</li><li>(2) Cryoablation</li> </ul> </ol><li>Phyllodes tumor</li><ol type="a"> <li>Bulky tumor derived from stromal cells</li><li>Most often benign but can be malignant in some cases</li><ul> <li>Hypercellular stroma with mitoses are signs of malignancy.
<blockquote style="color: blue; ">Phyllodes tumor: benign, borderline, or malignant; depends on stromal cellularity</blockquote></li> </ul><li>Lobulated tumor with cystic spaces containing leaf-like extensions</li><ul> <li>Often reach massive size</li> </ul><li>Treat by wide excision.</li> </ol><li>Intraductal papilloma</li><ol type="a"> <li>Most common cause of bloody nipple discharge in women < 50 years old
<blockquote style="color: blue; ">Intraductal papilloma: most common cause of bloody nipple discharge in women < 50 years old</blockquote></li><li>Develop in the lactiferous ducts or sinuses</li><li>No increased risk for cancer</li><li>Surgically remove the duct or sinus.</li> </ol> </ol>
</div></html>
<html><a name="HC021066"></a> <br><a name="PB021004"></a><div class="BB" style="color: rgb(47, 79, 79); ">A <b>winged scapula</b> may occur due to damage of the long thoracic nerve. There is also a danger for developing lymphedema
<blockquote style="color: blue; ">Winged scapula: damage to long thoracic nerve</blockquote></div><a name="P021088"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common cancer in adult women (1:8 lifetime risk)
<blockquote style="color: blue; ">Breast cancer: most common cancer in women</blockquote></li><ul> <li>(1) Mean age is 64 years old.</li><li>(2) Risk increases with age.</li> </ul><li>Most common breast mass in women > 50 years old</li><li>Slightly decreasing in incidence due to early detection and treatment</li><li>Second most common cancer-producing death in women</li><ul> <li>It is also the second most common cancer producing death in adults (includes men and women as a group).</li> </ul> </ol><li>Risk factors
<blockquote style="color: blue; ">Breast cancer risk: prolonged estrogen stimulation, genetically susceptible background</blockquote></li><ol type="a"> <li>Common denominators for increased risk of cancer</li><ul> <li>(1) Prolonged estrogen stimulation</li><li>(2) Genetically susceptible background</li> </ul><li>Family history and genetics</li><ul> <li>(1) Increased risk if breast cancer involves first-generation relatives</li><ul> <li>Mother, sister</li> </ul><li>(2) Genetic basis is involved in <10% of cases (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>).
<blockquote style="color: blue; ">Genetic basis: <10%</blockquote></li><ul> <li>(a) Autosomal dominant <i>BRCA1</i> and <i>BRCA2</i> association</li><ul> <li>Breasts or ovaries are frequently prophylactically removed.</li> </ul><li>(b) Li-Fraumeni multicancer syndrome</li><ul> <li>Inactivation of <i>TP53</i> suppressor gene</li> </ul> </ul><li>(3) Other gene relationships</li><ul> <li><i>RAS</i> oncogene, <i>ERBB2, RB</i> suppressor gene</li> </ul> </ul><li>Prolonged estrogen stimulation</li><ul> <li>(1) Early menarche/late menopause</li><li>(2) Nulliparity</li><li>(3) Postmenopausal obesity</li><ul> <li>Aromatization of androstenedione to estrone</li> </ul><li>(4) Hormone replacement therapy</li> </ul><li>Atypical ductal hyperplasia</li><li>Endometrial cancer, ionizing radiation, smoking cigarettes
<blockquote style="color: blue; ">Risk factors: unopposed estrogen; recent use of OCPs</blockquote></li><li>High breast density (determined by mammogram)</li><li>Recent use of OCPs; obesity after menopause</li><li>Use of postmenopausal hormone therapy (estrogen and progestin therapy)</li> </ol><li>Factors that decrease the risk for breast cancer
<blockquote style="color: blue; ">Factors reducing risk: breast-feeding; exercise; healthy body weight</blockquote></li><ol type="a"> <li>Breast-feeding</li><li>Moderate or vigorous physical training</li><li>Healthy body weight</li> </ol><li>Clinical findings
<blockquote style="color: blue; ">Clinical: painless mass; skin/nipple retraction</blockquote></li><ol type="a"> <li>Painless mass in the breast</li><ul> <li>Usually in the upper outer quadrant</li> </ul><li>Skin or nipple retraction</li><li>Painless axillary lymphadenopathy</li><li>Hepatomegaly; bone pain if metastasis has occurred</li> </ol><li>Mammography
<blockquote style="color: blue; ">Mammography: detect nonpalpable masses</blockquote></li><ol type="a"> <li>Primarily a screening test</li><ul> <li>Detects nonpalpable breast masses (detects 80-90%)</li> </ul><li>Does <i>not</i> distinguish benign from malignant lesions
<blockquote style="color: blue; ">Initial management of breast mass: fine needle aspiration</blockquote></li><li>Screening usually starts annually at age 40; earlier if patient is high risk</li><li>Identifies microcalcifications (<span>[[Fig. 21-38|Figure 21-38]]</span>) and spiculated masses with or without microcalcifications (30-50%)</li><ul> <li>(1) Most often occur in ductal carcinoma in situ (DCIS) and sclerosing adenosis
<blockquote style="color: blue; ">Microcalcifications: DCIS, sclerosing adenosis</blockquote></li><li>(2) Microcalcification pattern suggesting malignancy</li><ul> <li>Five or more tightly clustered microcalcifications that are punctate, microlinear, or branching</li> </ul> </ul> </ol><li>Types of breast cancer (<span>[[Table 21-5|Table 21-5. TYPES OF BREAST CANCER]]</span> and <span>[[Fig. 21-39|Figure 21-39]]</span>)</li><li>Natural history, treatment, and prognosis</li><ol type="a"> <li>Spread first by lymphatics and then hematogenously</li><ul> <li>(1) Outer quadrant cancer spreads to axillary nodes.</li><li>(2) Inner quadrant cancers spread to internal mammary nodes.</li> </ul><li>Extranodal metastasis</li><ul> <li>(1) Common sites of metastasis
<blockquote style="color: blue; ">Breast cancer: most common cancer metastatic to lungs and bone</blockquote></li><ul> <li>Lungs, bone, liver, brain, ovaries</li> </ul><li>(2) May metastasize 10 to 15 years after treatment</li><li>(3) Pain in bone metastasis is relieved with radiation.</li> </ul><li>Staging</li><ul> <li>(1) Extranodal metastasis has greater significance than nodal metastasis (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)
<blockquote style="color: blue; ">Breast cancer: extranodal spread has greater significance than nodal metastasis alone</blockquote></li><li>(2) Sentinel node biopsy</li><ul> <li>(a) Sampling of the initial node that drains the tumor
<blockquote style="color: blue; ">Sentinel node: initial node draining the tumor</blockquote></li><li>(b) If negative for metastasis, the other nodes in that group are usually negative.</li><li>(c) If positive for metastasis, there is a one-third chance that other nodes in that group have metastases.</li> </ul> </ul><li>Estrogen and progesterone receptor assays (ERA and PRA, respectively)</li><ul> <li>(1) Most often positive in postmenopausal women
<blockquote style="color: blue; ">ERA-PRA receptor assays: positive assay confers better prognosis</blockquote></li><li>(2) Clinical significance</li><ul> <li>(a) Confers an overall better prognosis</li><li>(b) Candidate for antiestrogen therapy with tamoxifen or raloxifene</li> </ul> </ul><li>Other tests performed on tissue</li><ul> <li>(1) S phase fraction</li><ul> <li>Above 5% is poor prognosis.</li> </ul><li>(2) DNA ploidy</li><ul> <li>Diploid tumor is better than an aneuploid tumor.</li> </ul><li>(3) <i>ERBB2</i> oncogene status
<blockquote style="color: blue; "><i>ERBB2</i> oncogene: if positive in breast tissue, poor prognosis</blockquote></li><ul> <li>Poor prognosis if amplification (multiple copies) is present (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>).</li> </ul> </ul><li>Treatment for high-risk patients <i>without</i> breast cancer</li><ul> <li>Treatment with tamoxifen or raloxifene reduces risk.</li> </ul><li>Surgical procedures</li><ul> <li>(1) Modified radical mastectomy; includes:</li><ul> <li>(a) Nipple/areolar complex</li><li>(b) All breast tissue</li><li>(c) Pectoralis minor</li><li>(d) Level I and II axillary lymph nodes in continuity</li><ul> <li>Level I nodes are inferior to the pectoralis minor muscle; level II nodes are beneath the pectoralis minor.</li> </ul><li>(e) Level III nodes if level I and II nodes are grossly involved</li><ul> <li>Level III nodes are medial and superior to the pectoralis minor.</li> </ul> </ul><li>(2) Breast conservation therapy
<blockquote style="color: blue; ">Breast conservation therapy has similar survival rate as modified radical mastectomy</blockquote></li><ul> <li>(a) Lumpectomy with microscopically free margins</li><li>(b) Sentinel node biopsy (preferable) or removal of level I and II axillary nodes</li><li>(c) Breast irradiation</li> </ul> </ul><li>Prognosis</li><ul> <li>(1) The 5-year relative survival rate for localized breast cancer (no node involvement) is 98%.</li><li>(2) The 5-year relative survival rate for breast cancer with nodal involvement is 84%.</li><li>(3) The 5-year relative survival rate for breast cancer with distant spread is 27%.</li><li>(4) Survival rate at 5 years for all stages combined is 89%.</li><li>(5) Survival rate at 10 years for all stages combined is 80%.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC021067"></a> <br><a name="P021089"></a><div class="PA" style="color: black; "><ol type="1"> <li>Benign glandular proliferation in the male breast due to estrogen
<blockquote style="color: blue; ">Gynecomastia: benign glandular proliferation of male breast tissue</blockquote></li><ol type="a"> <li>Subareolar mass (see <span>[[Fig. 18-9|Figure 18-9]]</span>)</li><li>More often unilateral than bilateral</li><li>Due to increased estrogen stimulation</li><ul> <li>(1) Increase in estrogen</li><li>(2) Decrease in androgens (leaves estrogen unopposed)</li><li>(3) Defect in androgen receptors (leaves estrogen unopposed)</li> </ul><li>Source of estrogen
<blockquote style="color: blue; ">Estrogen sources: peripheral aromatization of androgens; Leydig cells in testis</blockquote></li><ul> <li>(1) Peripheral aromatization (85%)</li><ul> <li>(a) Testosterone to estradiol</li><li>(b) Androstenedione to estrone</li> </ul><li>(2) Leydig cells (15%)</li> </ul> </ol><li>Physiologic gynecomastia
<blockquote style="color: blue; ">Gynecomastia: normal in newborn, adolescence, elderly</blockquote></li><ol type="a"> <li>Normal in the following:</li><ul> <li>(1) Newborn (60-90%)</li><li>(2) Puberty (peaks at ages 13-14 years)</li><li>(3) Elderly (occurs between 50-80 years of age)</li> </ul><li>In general, surgery is <i>not</i> indicated.</li> </ol><li>Pathologic gynecomastia
<blockquote style="color: blue; ">Gynecomastia: most common pathologic cause is cirrhosis (hyperestrinism)</blockquote></li><ol type="a"> <li>Cirrhosis</li><ul> <li>(1) Inability to metabolize estrogen</li><li>(2) Inability to metabolize 17-ketosteroids</li><ul> <li>Peripherally aromatized to estrone</li> </ul> </ul><li>Genetic diseases
<blockquote style="color: blue; ">Genetic causes: Klinefelter's syndrome, testicular feminization</blockquote></li><ul> <li>(1) Klinefelter's syndrome (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><ul> <li>Increased aromatization of androgens to estrogens in Leydig cells</li> </ul><li>(2) Testicular feminization (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><ul> <li>Decreased androgen receptor synthesis</li> </ul> </ul><li>Drugs
<blockquote style="color: blue; ">Drug causes: spironolactone, ketoconazole, DES, digoxin, flutamide, leuprolide</blockquote></li><ul> <li>(1) Drug displacement of estrogen from SHBG</li><ul> <li>Spironolactone, ketoconazole</li> </ul><li>(2) Drugs with estrogen activity</li><ul> <li>Diethylstilbestrol, digoxin (activates estrogen receptors)</li> </ul><li>(3) Drugs that block androgen receptors</li><ul> <li>Spironolactone, flutamide</li> </ul><li>(4) Drugs that decrease androgen production</li><ul> <li>Leuprolide</li> </ul> </ul><li>Cancer
<blockquote style="color: blue; ">Cancer causes: choriocarcinoma</blockquote></li><ul> <li>Choriocarcinoma of testis producing hCG (LH analogue)</li> </ul><li>Disorders with decreased androgen production</li><ul> <li>(1) Primary hypogonadism</li><ul> <li>Leydig cell dysfunction (refer to <span macro="tag [[20 Lower Urinary Tract and Male Reproductive Disorders]] [[Chapter 20]]"></span>)</li> </ul><li>(2) Secondary hypogonadism</li><ul> <li>Pituitary/hypothalamic dysfunction (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC021068"></a> <br><a name="P021090"></a><div class="PA" style="color: black; "><ol type="1"> <li>Risk factors
<blockquote style="color: blue; ">Breast cancer in men: Klinefelter's; inactivation of <i>BRCA2</i> suppressor gene</blockquote></li><ol type="a"> <li>Inactivation of <i>BRCA2</i> suppressor gene</li><li>Klinefelter's syndrome</li> </ol><li>Usually have a poor prognosis</li> </ol>
</div></html>
<html><a name="HC022002"></a> <br><a name="P022001"></a><div class="PA" style="color: black; "><ol type="1"> <li>Control an increase or decrease in hormone production
<blockquote style="color: blue; ">Negative feedback: ↑ calcium, ↓ PTH; ↓ calcium, ↑ PTH</blockquote></li><li>Example-increased calcium decreases parathyroid hormone (PTH).</li> </ol>
</div></html>
<html><a name="HC022003"></a> <br><a name="P022002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Evaluate hypofunctioning disorders</li><ul> <li>Example-adrenocorticotropic hormone (ACTH) stimulation test is used in the workup of hypocortisolism.
<blockquote style="color: blue; ">Endocrine gland hypofunction: use stimulation tests</blockquote></li> </ul><li>Causes of hypofunction</li><ol type="a"> <li>Autoimmune destruction</li><ul> <li>Examples-Addison's disease, Hashimoto's thyroiditis
<blockquote style="color: blue; ">Endocrine gland hypofunction: most common cause is autoimmune disease</blockquote></li> </ul><li>Infarction</li><ul> <li>Example-Sheehan's postpartum necrosis, Waterhouse-Friderichsen syndrome</li> </ul><li>Decreased hormone stimulation</li><ul> <li>Example-decreased thyroid-stimulating hormone in hypopituitarism</li> </ul><li>Enzyme deficiency, infection, neoplasia, congenital disorder</li> </ol> </ol>
</div></html>
<html><a name="HC022004"></a> <br><a name="P022003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Evaluate hyperfunctioning disorders
<blockquote style="color: blue; ">Endocrine gland hyperfunction: use suppression tests</blockquote></li><ul> <li>Example-dexamethasone suppression test evaluates hypercortisolism.</li> </ul><li>Most hyperfunctioning disorders <i>cannot</i> be suppressed.</li><ul> <li>Notable <i>exceptions</i> are prolactinoma and pituitary Cushing syndrome.
<blockquote style="color: blue; ">Endocrine gland hyperfunction: pituitary Cushing syndrome and prolactinoma can suppress</blockquote></li> </ul><li>Causes of hyperfunction</li><ul> <li>Adenoma, acute inflammation, hyperplasia, cancer</li> </ul> </ol>
</div></html>
![[22.I.A.Negative feedback loops]]
<<tiddler [[22.I.A.Negative feedback loops]]>>
![[22.I.B.Stimulation tests]]
<<tiddler [[22.I.B.Stimulation tests]]>>
![[22.I.C.Suppression tests]]
<<tiddler [[22.I.C.Suppression tests]]>>
<html><a name="HC022006"></a> <br><a name="P022004"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Endocrine gland hyperfunction: most common cause is a benign adenoma</blockquote>
<ol type="1"> <li>Pituitary adenoma (see section IV)</li><ul> <li>Most common tumor affecting the hypothalamus</li> </ul><li>Craniopharyngioma (see section IV)</li><li>Midline hamartoma</li><ul> <li><i>Not</i> a neoplasm</li> </ul><li>Langerhans histiocytosis (refer to <span macro="tag [[13 Lymphoid Tissue Disorders]] [[Chapter 13]]"></span>)</li> </ol>
</div></html>
<html><a name="HC022007"></a> <br><a name="P022005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sarcoidosis (refer to <span macro="tag [[16 Upper and Lower Respiratory Disorders]] [[Chapter 16]]"></span>)</li><ul> <li>Produces granulomatous inflammation</li> </ul><li>Meningitis (refer to <span macro="tag [[25 Nervous System and Special Sensory Disorders]] [[Chapter 25]]"></span>)</li> </ol>
</div></html>
<html><a name="HC022008"></a> <br><a name="PB022001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>"True" precocious puberty</b> implies a central nervous system (CNS) origin for the disorder, but pseudo-precocious puberty implies a peripheral cause (e.g., adrenogenital syndrome). True precocious puberty in boys is the onset of puberty <i>before</i> 9 years of age. The most common cause is a midline hamartoma in the hypothalamus. True precocious puberty in girls is the onset of puberty <i>before</i> 8 years of age. In most cases, it is idiopathic and less likely to be caused by a midline hamartoma.
<blockquote style="color: blue; ">Precocious puberty: true if CNS origin, pseudo if peripheral cause</blockquote></div><a name="P022006"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Hypothalamic dysfunction: secondary hypopituitarism, CDI, ↑ prolactin; precocious puberty, visual field defects, mass effects (hydrocephalus)</blockquote>
<ol type="1"> <li>Secondary hypopituitarism</li><ul> <li><i>No</i> releasing hormones to stimulate the anterior pituitary</li> </ul><li>Central diabetes inspidus (CDI)</li><ul> <li>Antidiuretic hormone (ADH) is synthesized in the hypothalamus.</li> </ul><li>Hyperprolactinemia</li><ul> <li>Loss of dopamine inhibition causes galactorrhea.</li> </ul><li>Precocious puberty</li><ul> <li>Most common cause in boys is a midline hamartoma.</li> </ul><li>Visual field disturbances</li><ul> <li>Usually bitemporal hemianopia</li> </ul><li>Mass effects</li><ul> <li>Produces obstructive hydrocephalus (refer to <span macro="tag [[25 Nervous System and Special Sensory Disorders]] [[Chapter 25]]"></span>)</li> </ul><li>Growth disorders</li><ul> <li>Dwarfism in children</li> </ul><li>Kallmann's syndrome (refer to <span macro="tag [[20 Lower Urinary Tract and Male Reproductive Disorders]] [[Chapter 20]]"></span>)</li> </ol>
</div></html>
![[22.II.A.Tumors altering hypothalamic function]]
<<tiddler [[22.II.A.Tumors altering hypothalamic function]]>>
![[22.II.B.Inflammatory disorders altering hypothalamic function]]
<<tiddler [[22.II.B.Inflammatory disorders altering hypothalamic function]]>>
![[22.II.C.Clinical findings of hypothalamic dysfunction]]
<<tiddler [[22.II.C.Clinical findings of hypothalamic dysfunction]]>>
<html><a name="HC022010"></a> <br><a name="P022007"></a><div class="PA" style="color: black; "><ol type="1"> <li>Midline location above the quadrigeminal plate
<blockquote style="color: blue; ">Pineal gland: midline above quadrigeminal plate</blockquote></li><li>Site for melatonin production</li><ol type="a"> <li>Superior cervical sympathetic ganglia stimulates receptors on pinealocytes.</li><ul> <li>Causes release of melatonin into spinal fluid and blood</li> </ul><li>Melatonin functions
<blockquote style="color: blue; ">Melatonin: chemical messenger of darkness</blockquote></li><ul> <li>(1) Important in sleep/moods and circadian rhythms</li><ul> <li>Released at night</li> </ul><li>(2) Used in the treatment of sleep and mood disorders</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC022011"></a> <br><a name="P022008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Dystrophic calcification of the pineal gland begins in childhood.
<blockquote style="color: blue; ">Pineal gland: commonly undergoes dystrophic calcification</blockquote></li><ol type="a"> <li>Useful in showing shifts due to mass lesions in the brain</li><li>Approximately 80% are calcified between 70 and 80 years old.</li> </ol><li>Pineal tumors</li><ol type="a"> <li>Majority are germ cell tumors resembling seminomas.
<blockquote style="color: blue; ">Pineal gland: majority are germ cell tumors</blockquote></li><li>Minority of tumors are teratomas.</li> </ol> </ol>
</div></html>
<html><a name="HC022012"></a> <br><a name="P022009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Visual disturbances</li><ul> <li>Paralysis of upward conjugate gaze (Parinaud's syndrome; see <span>[[Fig. 25-5|Figure 25-5]]</span>)
<blockquote style="color: blue; ">Pineal gland tumors: paralysis of upward gaze ("setting sun" sign)</blockquote></li> </ul><li>Obstructive hydrocephalus</li><ul> <li>Due to compression of the aqueduct of Sylvius in the third ventricle</li> </ul> </ol>
</div></html>
![[22.III.A.Clinical anatomy]]
<<tiddler [[22.III.A.Clinical anatomy]]>>
![[22.III.B.Disorders]]
<<tiddler [[22.III.B.Disorders]]>>
![[22.III.C.Clinical findings]]
<<tiddler [[22.III.C.Clinical findings]]>>
<html><a name="HC022014"></a> <br><a name="PB022002"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Rathke's pouch</b> is an ectodermal derivative derived from the oral cavity. It develops into the anterior lobe of the pituitary gland.</div><a name="PB022003"></a><div class="BB" style="color: rgb(47, 79, 79); ">The <b>pituitary gland</b> doubles in size during pregnancy due to synthesis of prolactin. Prolactin release is inhibited by estrogen and progesterone during pregnancy.</div><a name="P022010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Partial or complete loss of secretion of one or more hormones</li><ul> <li>Infarctions of the pituitary invariably lead to panhypopituitarism
<blockquote style="color: blue; ">Pituitary infarction: invariably produces panhypopituitarism</blockquote></li> </ul><li>Increased incidence of vascular or cerebrovascular disease</li><li>Types of pituitary dysfunction</li><ul> <li>(1) Primary hypopituitarism (pituitary dysfunction)</li><ul> <li>Approximately 75% of the gland must be destroyed.</li> </ul><li>(2) Secondary hypopituitarism (hypothalamic dysfunction)</li><ul> <li>Decreased hypothalamic releasing factors</li> </ul> </ul> </ol><li>Causes of hypopituitarism</li><ol type="a"> <li>Nonfunctioning (null) pituitary adenoma (<span>[[Fig. 22-1|Figure 22-1]]</span>)
<blockquote style="color: blue; ">Hypopituitarism in adults: most common cause is nonfunctioning adenoma</blockquote></li><ul> <li>(1) Most common cause</li><li>(2) Microadenoma < 10 mm; macroadenoma > 10 mm</li><li>(3) Association with multiple endocrine neoplasia (MEN) I syndrome
<blockquote style="color: blue; ">MEN I: pituitary adenoma, hyperparathyroidism, pancreatic tumor</blockquote></li><li>(4) MEN I syndrome findings include pituitary adenoma, hyperparathyroidism, pancreatic tumor (Zollinger-Ellison syndrome or insulinoma).</li> </ul><li>Craniopharyngioma</li><ul> <li>(1) Most common cause of hypopituitarism in children
<blockquote style="color: blue; ">Hypopituitarism in children: most common cause is craniopharyngioma</blockquote></li><li>(2) Benign pituitary tumor derived from Rathke's pouch remnants</li><li>(3) Located <i>above</i> the sella turcica
<blockquote style="color: blue; ">Rathke's pouch: develops anterior pituitary</blockquote></li><ul> <li>Extends into sella turcica and destroys the gland</li> </ul><li>(4) Cystic tumor with hemorrhage and calcification</li><li>(5) Commonly causes bitemporal hemianopia</li><li>(6) May produce central diabetes insipidus</li> </ul><li>Sheehan's postpartum necrosis</li><ul> <li>(1) Hypovolemic shock (e.g., blood loss) causes infarction.
<blockquote style="color: blue; ">Sheehan's postpartum necrosis: sudden cessation of lactation; pituitary infarction secondary to shock</blockquote></li><li>(2) Sudden cessation of lactation due to loss of prolactin</li><ul> <li>Eventual development of hypopituitarism</li> </ul> </ul><li>Pituitary apoplexy</li><ul> <li>(1) Term "apoplexy" refers to a sudden onset of neurologic dysfunction</li><li>(2) Most often due to hemorrhage/infarction of preexisting pituitary adenoma</li><li>(3) Predisposing factors</li><ul> <li>Trauma, pregnancy (Sheehan's postpartum necrosis, a nontumorous cause), treatment of a prolactinoma with bromocriptine</li> </ul><li>(4) Clinical findings; sudden onset of</li><ul> <li>(a) Headache, mental status dysfunction, visual disturbances</li><li>(b) Hormone dysfunction
<blockquote style="color: blue; ">Pituitary apoplexy: hemorrhage into preexisting adenoma</blockquote></li> </ul> </ul><li>Sickle cell anemia</li><ul> <li>Pituitary infarction from vascular occlusion by irreversibly sickled cells</li> </ul><li>Lymphocytic hypophysitis</li><ul> <li>(1) Female dominant autoimmune destruction of the pituitary gland</li><li>(2) Occurs during or after pregnancy
<blockquote style="color: blue; ">Lymphocytic hypophysitis: autoimmune destruction; occurs during or after pregnancy</blockquote></li> </ul><li>Empty sella syndrome</li><ul> <li>(1) Epidemiology</li><ul> <li>(a) Radiologic studies show an empty sella turcica.</li><li>(b) Primary and secondary types</li> </ul><li>(2) Primary type
<blockquote style="color: blue; ">Empty sella syndrome: subarachnoid space extends into sella; ↑ CSF pressure compresses gland</blockquote></li><ul> <li>(a) Anatomic defect above pituitary</li><li>(b) Subarachnoid space extends into sella turcica and fills up with cerebrospinal fluid (CSF).</li><li>(c) Increase in pressure on the pituitary gland causes it to flatten out.</li><li>(d) Often associated with women who are obese and have high blood pressure
<blockquote style="color: blue; ">Empty sella syndrome: obese with hypertension</blockquote></li> </ul><li>(3) Secondary type</li><ul> <li>Regression in size due to radiation, trauma, surgery</li> </ul> </ul><li>Hypothalamic dysfunction (see section II)</li> </ol><li>Clinical and laboratory findings of pituitary hypofunction (<span>[[Table 22-1|Table 22-1. CLINICAL FINDINGS IN HYPOPITUITARISM]]</span> and <span>[[Fig. 22-2|Figure 22-2]]</span>)</li><li>Diagnosis</li><ol type="a"> <li>CT scan or MRI (better test) of sella turcica</li><li>Stimulation tests for the various deficiencies</li> </ol><li>Treatment</li><ol type="a"> <li>Surgery for tumors (usually transsphenoidal)</li><li>Hormone replacement for deficiencies</li> </ol> </ol>
</div></html>
<html><a name="HC022015"></a> <br><a name="P022011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Normal function of posterior pituitary</li><ol type="a"> <li>Stores ADH</li><ul> <li>(1) Controls total body water</li><li>(2) Presence of ADH produces concentration of urine.</li><li>(3) Absence of ADH produces dilution of urine.
<blockquote style="color: blue; ">Posterior pituitary: storage of ADH and release of oxytocin</blockquote></li> </ul><li>Releases oxytocin</li><ul> <li>Produces milk ejection and uterine contractions</li> </ul> </ol><li>Refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span> for discussion of diabetes insipidus</li> </ol>
</div></html>
<html><a name="HC022016"></a> <br><a name="P022012"></a><div class="PA" style="color: black; "><ol type="1"> <li>Prolactinoma</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Benign adenoma
<blockquote style="color: blue; ">Prolactinoma: most common pituitary tumor</blockquote></li><li>(2) Overall most common pituitary tumor (35%)</li><li>(3) Secrete growth hormone as well in 7% of cases</li> </ul><li>Clinical and laboratory findings
<blockquote style="color: blue; ">Prolactinoma: secondary amenorrhea + galactorrhea</blockquote></li><ul> <li>(1) Women</li><ul> <li>(a) Secondary amenorrhea</li><ul> <li>Prolactin inhibits gonadotropin-releasing hormone (GnRH).</li> </ul><li>(b) Galactorrhea (see <span>[[Fig. 21-34|Figure 21-34]]</span>)</li> </ul><li>(2) Men</li><ul> <li>(a) Impotence
<blockquote style="color: blue; ">Prolactinoma in men: impotence due to loss of libido; headache</blockquote></li><ul> <li>Loss of libido due to decrease in testosterone</li> </ul><li>(b) Headache</li><ul> <li>Tumors tend to be larger than in women.</li> </ul><li>(c) <i>Not</i> enough estrogen-dependent breast tissue to produce galactorrhea</li> </ul><li>(3) Serum prolactin level is usually >200 ng/mL.</li><li>(4) Decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH)</li><ul> <li>Due to decreased GnRH</li> </ul> </ul><li>Other causes of galactorrhea (refer to <span macro="tag [[21 Female Reproductive Disorders and Breast Disorders]] [[Chapter 21]]"></span>)</li><li>Treatment
<blockquote style="color: blue; ">Rx prolactinoma: dopamine analogues; surgery</blockquote></li><ul> <li>(1) Dopamine analogues (e.g., cabergoline)</li><ul> <li>(a) Tumor does respond to suppression.</li><ul> <li>Shrinks in <50% of cases</li> </ul><li>(b) Restores gonadal function in 70% to 90% of cases</li> </ul><li>(2) Surgery if macroadenomas</li> </ul> </ol><li>Growth hormone (GH) adenoma</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Accounts for 20% of all pituitary adenomas</li><li>(2) Functions of GH
<blockquote style="color: blue; ">GH: gluconeogenesis; ↑ amino acid uptake in muscle; stimulate IGF-1 in liver</blockquote></li><ul> <li>(a) Stimulates liver synthesis/release of insulin growth factor (IGF)-1</li><li>(b) Stimulates gluconeogenesis and amino acid uptake in muscle</li><li>(c) Negative feedback relationship with glucose and IGF-1</li><li>(d) Antinatriuretic action (retains sodium)</li> </ul><li>(3) Functions of IGF-1
<blockquote style="color: blue; ">IGF-1: stimulates bone, cartilage, soft tissue growth</blockquote></li><ul> <li>Stimulates growth of bone (linear and lateral), cartilage, soft tissue</li> </ul> </ul><li>Clinical and laboratory findings</li><ul> <li>(1) Children develop gigantism.
<blockquote style="color: blue; ">Gigantism: ↑ linear/lateral bone growth in children; epiphyses <i>not</i> fused</blockquote></li><ul> <li>(a) Due to increased linear bone growth (epiphyses have not fused)</li><li>(b) Lateral bone growth also increased</li> </ul><li>(2) Adults develop acromegaly (<span>[[Fig. 22-3|Figure 22-3]]</span>)</li><ul> <li>(a) Increased lateral bone growth (e.g., hands, feet, jaw)
<blockquote style="color: blue; ">Acromegaly: ↑ lateral bone growth only (epiphyses not fused), organomegaly, hyperglycemia</blockquote></li><ul> <li><i>No</i> linear growth because epiphyses are fused</li> </ul><li>(b) Prominent jaw</li><ul> <li>Spacing between the teeth</li> </ul><li>(c) Frontal bossing</li><ul> <li>Enlarged frontal sinus increases the hat size.
<blockquote style="color: blue; ">Acromegaly: comparing old versus new photograph is valuable diagnostic tool</blockquote></li> </ul><li>(d) Macroglossia, cardiomyopathy (cause of death)</li> </ul><li>(3) Increased GH and IGF-1 (more sensitive test than GH)</li><ul> <li>Hormones are <i>not</i> suppressed by glucose administration.</li> </ul><li>(4) Hyperglycemia</li><ul> <li>Due to increase in gluconeogenesis</li> </ul><li>(5) Hypertension
<blockquote style="color: blue; ">Acromegaly: heart failure from cardiomyopathy is a common cause of death</blockquote></li><ul> <li>Sodium retention related to increased GH and insulin (hyperglycemia increases its release)</li> </ul><li>(6) Visceral organomegaly with dysfunction</li><ul> <li>Heart, liver, kidneys, thyroid</li> </ul><li>(7) Muscle weakness (myopathy); cardiomyopathy</li><li>(8) Headache and visual field defects</li><ul> <li>Enlarged sella turcica</li> </ul> </ul><li>Diagnosis</li><ul> <li>(1) Imaging with CT scan, MRI (best study)</li><li>(2) Suppression tests</li> </ul><li>Treatment</li><ul> <li>(1) Transsphenoidal surgery</li><li>(2) If surgery does not correct</li><ul> <li>Somatostatin and dopamine analogues; GH receptor antagonists</li> </ul> </ul> </ol><li>Syndrome of inappropriate ADH (SIADH)</li><ul> <li>Refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span> for complete discussion of SIADH</li> </ul> </ol>
</div></html>
![[22.IV.A.Anterior pituitary hypofunction]]
<<tiddler [[22.IV.A.Anterior pituitary hypofunction]]>>
![[22.IV.B.Posterior pituitary hypofunction]]
<<tiddler [[22.IV.B.Posterior pituitary hypofunction]]>>
![[22.IV.C.Pituitary hyperfunction disorders]]
<<tiddler [[22.IV.C.Pituitary hyperfunction disorders]]>>
<html><a name="HC022046"></a> <br><a name="P022060"></a><div class="PA" style="color: black; "><ol type="1"> <li>Affects 5% to 7% of population in the United States</li><ul> <li>Increased in Native Americans (35% of Pima Indians)</li> </ul><li>Leading cause in the United States for
<blockquote style="color: blue; ">DM most common cause of blindness, peripheral neuropathy, chronic renal failure, below-knee amputation</blockquote></li><ol type="a"> <li>Legal blindness</li><li>Peripheral neuropathy</li><li>Chronic renal failure</li><li>Below-the-knee amputation</li> </ol><li>Incidence increases with age.</li> </ol>
</div></html>
<html><a name="HC022047"></a> <br><a name="P022061"></a><div class="PA" style="color: black; "><ol type="1"> <li>Type 1 and type 2 diabetes mellitus (<span>[[Table 22-11|Table 22-11. COMPARISON BETWEEN TYPE 1 AND TYPE 2 DIABETES MELLITUS]]</span>)</li><li>Secondary causes</li><ol type="a"> <li>Pancreatic disease</li><ul> <li>Examples-cystic fibrosis, chronic pancreatitis</li> </ul><li>Drugs</li><ul> <li>Examples-glucocorticoids, pentamidine, thiazides, α-interferon</li> </ul><li>Endocrine disease</li><ul> <li>Examples-pheochromocytoma, glucagonoma, Cushing syndrome</li> </ul><li>Genetic disease</li><ul> <li>Examples-hemochromatosis, syndrome X (metabolic syndrome), maturity onset diabetes of the young (MODY)</li> </ul><li>Insulin-receptor deficiency</li><ul> <li>Acanthosis nigricans is a phenotypic marker.</li> </ul><li>Infections</li><ul> <li>Examples-mumps, cytomegalovirus (AIDS patients)</li> </ul> </ol><li>Impaired glucose tolerance (IGT)</li><li>Gestational diabetes mellitus (GDM)</li><li>Maturity onset diabetes of the young (MODY)</li><ol type="a"> <li>Autosomal dominant (AD) inheritance</li><ul> <li>(1) Various subtypes</li><li>(2) Mutations of transcription factor genes (e.g., glucokinase gene)
<blockquote style="color: blue; ">MODY: AD inheritance; not obese; impaired glucose-induced secretion of insulin</blockquote></li> </ul><li>Patients < 25 years old and are <i>not</i> obese.</li><li>Mild to severe hyperglycemia</li><ul> <li>Impaired glucose-induced secretion of insulin release</li> </ul><li>Resistance to ketosis</li><li>May progress into type 2 diabetes mellitus</li><li>Treatment varies with regard to oral hypoglycemic agents or insulin.</li> </ol><li>Metabolic syndrome</li><ol type="a"> <li>May affect as high as 25% of the U.S. population</li><li>Insulin resistance syndrome
<blockquote style="color: blue; ">Metabolic syndrome: insulin resistance exacerbated by obesity</blockquote></li><ul> <li>(1) Genetic defect causes insulin resistance that is exacerbated by obesity.</li><li>(2) Commonly associated with polycystic ovary syndrome in women</li><li>(3) May be associated with acanthosis nigricans (refer to <span macro="tag [[24 Skin Disorders]] [[Chapter 24]]"></span>)
<blockquote style="color: blue; ">Associations: acanthosis nigricans; Alzheimer's disease</blockquote></li><li>(4) Increased risk for developing Alzheimer's disease (refer to <span macro="tag [[25 Nervous System and Special Sensory Disorders]] [[Chapter 25]]"></span>)</li> </ul><li>Clinical and laboratory findings</li><ul> <li>(1) Hyperinsulinemia; leads to
<blockquote style="color: blue; ">Hyperinsulinemia: ↑ VLDL, hypertension, CAD; ↓HDL-CH</blockquote></li><ul> <li>(a) Increased synthesis of very low-density lipoprotein (VLDL; hypertriglyceridemia)</li><ul> <li>Serum triglyceride ≥ 150 mg/dL</li> </ul><li>(b) Hypertension (≥130/85 mm Hg)</li><ul> <li>Increased insulin increases sodium retention by the renal tubules.</li> </ul><li>(c) Coronary artery disease (CAD)</li><ul> <li>Increased insulin damages endothelial cells.</li> </ul> </ul><li>(2) Obesity exacerbates insulin resistance.</li><ul> <li>Increased adipose downregulates insulin receptor synthesis.</li> </ul><li>(3) Definition for obesity in metabolic syndrome</li><ul> <li>(a) Abdominal waistline girth in men > 40 inches (102 cm)</li><li>(b) Abdominal waistline girth in women > 35 inches (88 cm)</li> </ul><li>(4) Serum high-density lipoprotein cholesterol (HDL-CH) < 40 mg/dL in men and <50 mg/dL in women</li><li>(5) Fasting serum glucose ≥ 110 mg/dL</li> </ul><li>Treatment</li><ul> <li>(1) Statin drugs to lower lipids</li><li>(2) Treat hypertension</li><ul> <li>Angiotensin-converting enzyme (ACE) inhibitors or diuretics</li> </ul><li>(3) Correct insulin resistance with weight loss.</li><li>(4) Correct insulin resistance with drugs.</li><ul> <li>? Metformin, thiazolidinediones</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC022048"></a><span>[[Table 22-12|Table 22-12. COMPLICATIONS OF DIABETES MELLITUS]]</span> <br> <br><a name="P022062"></a><div class="PA" style="color: black; "><ol type="1"> <li>Poor glycemic control</li><ol type="a"> <li>Hyperglycemia is the key factor that produces organ damage.
<blockquote style="color: blue; ">Good glycemic control prevents complications of diabetes.</blockquote></li><li>Glucose control reduces onset and severity of complications.</li><ul> <li>Complications are related to retinopathy, neuropathy, and nephropathy in descending order.</li> </ul> </ol><li>Nonenzymatic glycosylation (NEG)
<blockquote style="color: blue; ">NEG: Hb<sub>A1c,</sub> hyaline arteriolosclerosis, glomerulopathy</blockquote></li><ol type="a"> <li>Glucose combines with amino groups in proteins.</li><li>Produces advanced glycosylation products</li><ul> <li>(1) Increased vessel permeability to protein</li><li>(2) Increased atherogenesis</li> </ul><li>Role in diabetes</li><ul> <li>(1) Production of glycosylated Hb<sub>A1c</sub></li><li>(2) Hyaline arteriolosclerosis (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)</li><li>(3) Diabetic glomerulopathy (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)</li><li>(4) Ischemic heart disease, strokes, peripheral vascular disease</li> </ul> </ol><li>Osmotic damage</li><ol type="a"> <li>Aldose reductase
<blockquote style="color: blue; ">Aldose reductase: converts glucose to sorbitol; osmotic damage</blockquote></li><ul> <li>(1) Converts glucose to sorbitol</li><li>(2) Sorbitol draws water into tissue causing damage.</li> </ul><li>Role in diabetes mellitus</li><ul> <li>(1) Formation of cataracts</li><li>(2) Peripheral neuropathy</li><ul> <li>(a) Osmotic damage of Schwann cells produces demyelination and sensorimotor peripheral neuropathy</li><li>(b) Peripheral neuropathy leads to neuropathic pressure ulcers (<span>[[Fig. 22-26|Figure 22-26]]</span>).</li><ul> <li>Patient cannot feel pain.</li> </ul> </ul><li>(3) Retinopathy</li><ul> <li>Osmotic damage to pericytes produces microaneurysms of retinal vessels (<span>[[Fig. 22-27|Figure 22-27]]</span>).
<blockquote style="color: blue; ">Osmotic damage: cataracts, peripheral neuropathy, retinopathy</blockquote></li> </ul> </ul> </ol><li>Diabetic microangiopathy</li><ol type="a"> <li>Increased synthesis of type IV collagen in basement membranes and mesangium</li><li>Important in diabetic glomerulopathy (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)
<blockquote style="color: blue; ">Microangiopathy: diabetic glomerular disease</blockquote></li> </ol> </ol>
</div></html>
<html><a name="HC022049"></a> <br><a name="PB022006"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>General treatment for type 1 diabetes. Split dose insulin mixtures:</b> split doses of regular insulin + neutral protamine hagedorn (NPH) twice daily (morning [<span style="font-variant:small-caps;">am</span>] and evening [<span style="font-variant:small-caps;">pm</span>]). <b>Intensive insulin therapy</b> involves three injections, including regular insulin + NPH in the <span style="font-variant:small-caps;">am</span>; regular insulin to cover <span style="font-variant:small-caps;">pm</span> dinner; and NPH at bedtime. <b>Long-acting insulin</b> may be used for maintaining a basal level throughout the day plus insulin lispro (peaks at 13 hours) to cover each meal. <b>Pramlintide</b> is a synthetic analogue of human amylin, which is a hormone normally secreted along with insulin by β-islet cells. It can be used as adjunctive treatment in type 1 or 2 diabetics who inject insulin at meal time. An <b>insulin pump</b> allows continuous infusion of insulin throughout the day at preset levels. It is also possible to program doses of insulin as needed at meal times. In patients on a split dose insulin regimen, a problem may occur in evaluating the cause of an increased early morning glucose level. To sort out the cause of the hyperglycemia, a 3 <span style="font-variant:small-caps;">am</span> glucose is useful. If both the 3 <span style="font-variant:small-caps;">am</span> and 7 <span style="font-variant:small-caps;">am</span> glucose levels are increased, more NPH insulin is required at dinner or bedtime (called the waning effect). If the 3<span style="font-variant:small-caps;">am</span> glucose is decreased and the 7 <span style="font-variant:small-caps;">am</span> glucose is increased, then less NPH insulin should be given at dinner or bedtime. This phenomenon (called Somogyi effect) is caused by the rebound release of counterregulatory hormones (e.g., glucagon, catecholamines) in response to the hypoglycemia at 3 <span style="font-variant:small-caps;">am</span>. If the 3 <span style="font-variant:small-caps;">am</span> glucose is normal but the 7 <span style="font-variant:small-caps;">am</span> glucose is increased, this is called the dawn effect. It is caused by the release of growth hormone at 5 <span style="font-variant:small-caps;">am</span>. Growth hormone is gluconeogenic; hence, it has an anti-insulin effect. Dividing the NPH dose between dinner and bedtime usually corrects this problem. If the lunch time glucose is high, then more regular insulin should be given in the <span style="font-variant:small-caps;">am</span>. If the glucose is increased at dinner time, then more NPH should be given at breakfast.</div><a name="PB022007"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>General principles in treatment of DKA.</b> Volume replacement is the most important initial step in management of DKA because of the tremendous loss of water and sodium in the urine by osmotic diuresis. Patients are frequently in hypovolemic shock. Volume replacement with crystalloids is best accomplished with 0.9% normal saline until the volume deficit is corrected and the patient is stabile with regard to blood pressure and mental status. At this point, the infusion is switched to 5% dextrose in 0.45% saline and insulin therapy is initiated. Serum glucose, electrolytes, arterial blood gases, and serum ketones should all be closely monitored throughout treatment. Particular concerns related to treatment with insulin include hypophosphatemia (phosphate goes along with glucose into the cell) and hypokalemia (lost in the urine by osmotic diuresis). It should be understood that the hyperkalemia that one initially sees in DKA is most often related to a transcellular shift of potassium moving out of the cell as hydrogen ions move in for buffering (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>). Total body potassium is in fact decreased in DKA, because it is lost along with sodium in the urine by osmotic diuresis. Hence, when the pH is restored to normal and there is no transcellular shift, the physician often finds a very low serum potassium. Severe hypokalemia or hypophosphatemia can cause respiratory paralysis; hence, monitoring potassium and phosphorus levels is very important once insulin therapy is initiated.</div><a name="PB022008"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>General principles in treatment of type 2 diabetes mellitus.</b> Oral hypoglycemic agents are most often used in treatment, because most patients are <i>not</i> insulin deficient. The primary mechanism of action (MOA) of <b>metformin</b> is to decrease hepatic output of glucose. Because metformin, a biguanide, does <i>not</i> produce hypoglycemia, it is a preferred drug for most patients. Side effects include diarrhea and lactic acidosis. <b>Sulfonylureas</b> (e.g., glyburide, glipizide) increase pancreatic secretion of insulin. They are a common cause of hypoglycemia in a type 2 diabetic. <b>Acarbose</b> and <b>miglitol</b> inhibit α-glucosidase. In this regard, they work by competitively inhibiting pancreatic amylase and small intestinal glucosidases from breaking down glucose in the bowel, hence decreasing glucose reabsorption after eating. Side effects include flatulence and diarrhea. <b>Pioglitazone</b> and <b>rosiglitazone</b> (thiazolidinediones) increase insulin sensitivity. They accomplish this by decreasing peripheral insulin resistance, increasing glucose disposal, and decreasing hepatic glucose production. Side effects include hepatotoxicity with an increase in serum transaminases. <b>Repaglinide</b> and <b>nateglinide</b> (meglitinides) acutely increase pancreatic insulin secretion as their MOA. Hypoglycemia may occur as a side effect. <b>Exenatide</b> is a synthetic peptide that stimulates release of insulin from pancreatic β-islet cells. Combinations of oral hypoglycemic drugs are commonly used if one drug does <i>not</i> produce adequate glycemic control. If oral hypoglycemic agents alone or in combination are still ineffective in glycemic control, then insulin is utilized.</div><a name="P022063"></a><div class="PA" style="color: black; "><ol type="1"> <li>Insulin-induced hypoglycemia</li><ol type="a"> <li>Most common complication</li><li>Produces irreversible brain damage by destroying neurons
<blockquote style="color: blue; ">Insulin-induced hypoglycemia: most common complication of diabetes</blockquote></li><li>Clinical findings</li><ul> <li>(1) Sympathetic nervous system signs</li><ul> <li>Sweating, tachycardia, palpitations, and tremulousness</li> </ul><li>(2) Parasympathetic nervous system signs</li><ul> <li>Nausea and hunger</li> </ul><li>(3) Focal neurologic deficits, mental confusion, coma</li> </ul> </ol><li>Diabetic ketoacidosis (DKA; <span>[[Fig. 22-28|Figure 22-28]]</span>)
<blockquote style="color: blue; ">DKA: complication of type 1 DM</blockquote></li><ol type="a"> <li>Complication of type 1 diabetes</li><li>Precipitated by medical illness or omission of insulin</li><li>Produces severe volume depletion and coma</li><ul> <li>Volume depletion due to loss of sodium and water with osmotic diuresis</li> </ul><li>Mechanisms for hyperglycemia
<blockquote style="color: blue; ">Gluconeogenesis: most important mechanism of hyperglycemia in diabetic ketoacidosis</blockquote></li><ul> <li>(1) Increased gluconeogenesis</li><ul> <li>(a) Due to increase in glucagon and epinephrine</li><li>(b) Most important mechanism of hyperglycemia</li> </ul><li>(2) Increased glycogenolysis in the liver</li> </ul><li>Mechanism for ketone bodies</li><ul> <li>(1) Increased lipolysis with release of fatty acids</li><ul> <li><i>No</i> inhibition of hormone-sensitive lipase</li> </ul><li>(2) Increased β-oxidation of fatty acids increases production of acetyl CoA.</li><ul> <li><i>No</i> malonyl Co-A to inhibit carnitine acyltransferase, the rate-limiting enzyme of β-oxidation</li> </ul><li>(3) Acetyl CoA is converted by the liver to ketone bodies.
<blockquote style="color: blue; ">Ketoacids: synthesized from acetyl CoA derived from β-oxidation of fatty acids</blockquote></li><ul> <li>Acetone (fruity odor), acetoacetic and β-hydroxybutyric acid</li> </ul> </ul><li>Mechanism for hypertriglyceridemia</li><ul> <li>(1) Lack of insulin decreases capillary lipoprotein lipase activity in peripheral blood.</li><li>(2) Accumulation of chylomicrons and VLDL in the blood
<blockquote style="color: blue; ">Hypertriglyceridemia: ↓ capillary lipoprotein lipase activity; ↓ hydrolysis of chylomicrons and VLDL</blockquote></li><ul> <li>Type V hyperlipoproteinemia (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)</li> </ul><li>(3) May precipitate acute pancreatitis and eruptive xanthomas in the skin</li><ul> <li>Called the hyperchylomicronemia syndrome</li> </ul> </ul><li>Laboratory findings</li><ul> <li>(1) Hyperglycemia</li><ul> <li>Glucose ranges from 250 to 1000 mg/dL.</li> </ul><li>(2) Increased Hb<sub>A1c</sub>≥ 6%</li><li>(3) Dilutional hyponatremia (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li><ul> <li>(a) Glucose overrides sodium in controlling the osmotic gradient.</li><li>(b) Water shifts out of the intracellular fluid compartment into the extracellular fluid compartment.</li> </ul><li>(4) Hyperkalemia (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)
<blockquote style="color: blue; ">DKA electrolytes: ↓ serum sodium, bicarbonate (metabolic acidosis); ↑ serum potassium, anion gap</blockquote></li><ul> <li>Transcellular shift as excess H<sup>+</sup> ions enter cells in exchange of potassium</li> </ul><li>(5) Increased anion gap metabolic acidosis (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li><ul> <li>Due to ketoacidosis and lactic acidosis</li> </ul><li>(6) Prerenal azotemia (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)</li><ul> <li>Due to volume depletion</li> </ul> </ul><li>Mortality rate in DKA is 5% to 10%.
<blockquote style="color: blue; ">Hyperomolar nonketotic coma: complication of type 2 DM</blockquote></li> </ol><li>Hyperosmolar nonketotic coma (see <span>[[Table 22-11|Table 22-11. COMPARISON BETWEEN TYPE 1 AND TYPE 2 DIABETES MELLITUS]]</span>)</li><ol type="a"> <li>Complication of type 2 diabetes</li><li>Increased mortality rate (20-50%)</li><ul> <li>Patients are older and usually have underlying cardiac and renal problems.</li> </ul> </ol> </ol>
</div></html>
![[22.IX.A.Epidemiology]]
<<tiddler [[22.IX.A.Epidemiology]]>>
![[22.IX.B.Classification]]
<<tiddler [[22.IX.B.Classification]]>>
![[22.IX.C.Pathologic processes and complications in diabetes mellitus (Table 22-12)]]
<<tiddler [[22.IX.C.Pathologic processes and complications in diabetes mellitus (Table 22-12)]]>>
![[22.IX.D.Clinical findings]]
<<tiddler [[22.IX.D.Clinical findings]]>>
![[22.IX.E.Laboratory diagnosis]]
<<tiddler [[22.IX.E.Laboratory diagnosis]]>>
![[22.IX.F.Impaired glucose tolerance (IGT)]]
<<tiddler [[22.IX.F.Impaired glucose tolerance (IGT)]]>>
![[22.IX.G.Gestational diabetes (GDM)]]
<<tiddler [[22.IX.G.Gestational diabetes (GDM)]]>>
<html><a name="HC022050"></a> <br><a name="P022064"></a><div class="PA" style="color: black; "><ol type="1"> <li>Criteria</li><ol type="a"> <li>Random plasma glucose ≥ 200 mg/dL plus classic symptoms</li><li>Fasting plasma glucose ≥ 126 mg/dL</li><ul> <li>Set for high sensitivity</li> </ul><li>Two-hour glucose level after 75-g glucose challengeis ≥200 mg/dL.</li><li>One of the preceding three criteria must be present on a subsequent day to confirm the diagnosis of diabetes.</li> </ol><li>Glycosylated hemoglobin (Hb<sub>A1c</sub>)
<blockquote style="color: blue; ">Hb<sub>A1c</sub>: marker of long-term glycemic control</blockquote></li><ol type="a"> <li>Evaluates long-term glycemic control</li><li>Represents the mean glucose value for the preceding 8 to 12 weeks</li><li>Test is currently <i>not</i> used to diagnose diabetes.</li><li>Goal in therapy is <7% (some use 6.5%).</li> </ol><li>Fructosamine</li><ul> <li>Reflects glycemic control for the preceding 2 weeks</li> </ul> </ol>
</div></html>
<html><a name="HC022051"></a> <br><a name="P022065"></a><div class="PA" style="color: black; "><ol type="1"> <li>Patient has hyperglycemia that is nondiagnostic of diabetes.</li><ol type="a"> <li>Fasting glucose > 110 mg/dL, but <126 mg/dL</li><li>Two-hour glucose > 140 mg/dL, but <200 mg/dL after 75-g oral glucose tolerance test</li> </ol><li>Pathogenesis
<blockquote style="color: blue; ">IGT: prediabetic state; insulin resistance</blockquote></li><ul> <li>Prediabetic state with insulin resistance</li> </ul><li>Increased risk for macrovascular disease and neuropathy
<blockquote style="color: blue; ">GDM: anti-insulin effect of HPL, cortisol, progesterone</blockquote></li><li>Approximately 30% develop type 2 diabetes within 10 years.</li><li>Treatment is to exercise regularly and to reduce sugar intake.</li> </ol>
</div></html>
<html><a name="HC022052"></a> <br><a name="P022066"></a><div class="PA" style="color: black; "><ol type="1"> <li>Glucose intolerance develops during pregnancy.</li><ol type="a"> <li>Anti-insulin effect of human placental lactogen (HPL), cortisol, and progesterone</li><li>Increased risk for GDM in future pregnancies</li> </ol><li>Screening</li><ol type="a"> <li>All pregnant women are screened between 24 and 28 weeks' gestation.</li><li>50-g glucose challenge followed by 1-hour glucose level</li><ul> <li>Above 140 mg/dL is a positive screen.</li> </ul><li>Positive screen is confirmed with a 3-hour oral glucose tolerance test.</li> </ol><li>Newborn risks</li><ol type="a"> <li>Macrosomia
<blockquote style="color: blue; ">Macrosomia: ↑ insulin causes ↑ in adipose and muscle</blockquote></li><ul> <li>(1) Hyperglycemia in the fetus causes release of insulin.</li><li>(2) Insulin increases fat stored in adipose tissue.</li><li>(3) Insulin increases muscle mass by increasing amino acid uptake in muscle.</li> </ul><li>Respiratory distress syndrome (RDS)
<blockquote style="color: blue; ">RDS: ↑ insulin inhibits fetal surfactant production</blockquote></li><ul> <li>Insulin inhibits fetal surfactant production.</li> </ul><li>Increased risk for open neural tube defects</li><li>Neonatal hypoglycemia</li><ul> <li>High insulin levels at birth drives glucose into the hypoglycemic range (give newborn glucose after birth).
<blockquote style="color: blue; ">Neonatal hypoglycemia: ↑ insulin drives glucose into hypoglycemic range; give newborn glucose at birth</blockquote></li> </ul> </ol><li>Maternal risk</li><ul> <li>Diabetes may develop at a later date (>50% of cases).</li> </ul><li>If patients cannot keep their blood glucose in control by diet alone, then insulin is recommended.</li> </ol>
</div></html>
<html><a name="HC022018"></a> <br><a name="P022016"></a><div class="PA" style="color: black; "><ol type="1"> <li>Trapping of iodide is thyroid-stimulating hormone (TSH)-mediated.</li><li>Oxidation of iodides to iodine is peroxidase-mediated.</li><li>Organification</li><ol type="a"> <li>Iodine is incorporated into tyrosine to form MIT (monoiodotyrosine) and DIT (diiodotyrosine).</li><li>It is TSH-mediated.</li> </ol><li>Coupling of MIT with DIT produces triiodothyronine (T<sub>3</sub>).
<blockquote style="color: blue; ">Thyroid hormone: iodide attached to tyrosine</blockquote></li><li>Coupling of DIT with DIT produces thyroxine (T<sub>4</sub>).</li><li>Hormones are stored as colloid.</li><li>Proteolysis of colloid by lysosomal proteases is TSH-mediated.
<blockquote style="color: blue; ">TSH: mediates trapping, organification, and proteolysis</blockquote></li><li>T<sub>4</sub> and T<sub>3</sub> bind to thyroid-binding globulin (TBG).</li><ul> <li>One third of TBG binding sites are normally occupied.</li> </ul><li>Free T<sub>4</sub> (FT<sub>4</sub>) is peripherally converted to free T<sub>3</sub> (FT<sub>3</sub>) by an outer ring deiodinase.</li><ol type="a"> <li>FT<sub>3</sub> is a metabolically active hormone.
<blockquote style="color: blue; ">FT<sub>4</sub>: prohormone; rendered metabolically active by outer ring deiodinase (FT<sub>3</sub>)</blockquote></li><li>FT<sub>4</sub> is considered a prohormone.</li><li>FT<sub>4</sub> and FT<sub>3</sub> have a negative feedback relationship with TSH.</li><ul> <li>(1) An increase in FT<sub>4</sub>/FT<sub>3</sub> should produce a decrease in TSH.
<blockquote style="color: blue; ">FT<sub>4</sub>/FT<sub>3</sub>: negative feedback with TSH</blockquote></li><li>(2) A decrease in FT<sub>4</sub>/FT<sub>3</sub> should produce an increase in TSH.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC022019"></a> <br><a name="P022017"></a><div class="PA" style="color: black; "><ol type="1"> <li>Control of total energy expenditure</li><li>Growth and maturation of tissue</li><li>Turnover of hormones and vitamins</li><li>Cell regeneration</li> </ol>
</div></html>
<html><a name="HC022020"></a> <br><a name="P022018"></a><div class="PA" style="color: black; "><ol type="1"> <li>Total serum T<sub>4</sub> (<span>[[Fig. 22-4A|Figure 22-4]]</span>)</li><ol type="a"> <li>Represents T<sub>4</sub> bound to TBG and free (unbound) T<sub>4</sub> (FT<sub>4</sub>)
<blockquote style="color: blue; ">Total serum T<sub>4</sub>: T<sub>4</sub> bound to TBG + FT<sub>4</sub></blockquote></li><ul> <li>Note: the values used in the schematic do <i>not</i> represent true values for each of the components.</li> </ul><ul> <li>(1) <span>[[Figure 22-2A|Figure 22-2]]</span> shows one third of TBG binding sites on two TBGs occupied by T<sub>4</sub>.</li><ul> <li>Total of 6 T<sub>4</sub> bound to TBG</li> </ul><li>(2) There are 4 FT<sub>4</sub>.</li><li>(3) The total serum T<sub>4</sub> is 10.</li><li>(4) TSH is normal, because FT<sub>4</sub> is normal.</li> </ul><li>Increase in TBG synthesis increases total serum T<sub>4</sub> (<span>[[Fig. 22-4B|Figure 22-4]]</span>).</li><ul> <li>(1) Estrogen increases the synthesis of TBG.
<blockquote style="color: blue; ">Estrogen: ↑ TBG which ↑ total serum T<sub>4</sub> but <i>not</i> FT<sub>4</sub></blockquote></li><ul> <li>Pregnancy, oral contraceptive pill, hormone replacement</li> </ul><li>(2) Extra TBG automatically has one third of its binding sites occupied by T<sub>4</sub>.</li><ul> <li>Total of 9 T<sub>4</sub> bound to TBG</li> </ul><li>(3) The 3 T<sub>4</sub> used to bind to the extra TBG are replaced by 3 T<sub>4</sub> released from the thyroid gland.</li><li>(4) FT<sub>4</sub> remains normal (4).</li><li>(5) Total serum T<sub>4</sub> is increased (9 + 4 = 13).</li><li>(6) TSH is normal, because FT<sub>4</sub> is normal.</li><li>(7) <i>No</i> signs of thyrotoxicosis are present.</li> </ul><li>Decrease in TBG synthesis decreases total serum T<sub>4</sub>.</li><ul> <li>(1) Causes of a decreased TBG
<blockquote style="color: blue; ">↓TBG: ↓ total serum T<sub>4</sub> but <i>not</i> FT<sub>4</sub></blockquote></li><ul> <li>Anabolic steroids, nephrotic syndrome (urinary loss)</li> </ul><li>(2) Total serum T<sub>4</sub> is decreased.</li><li>(3) FT<sub>4</sub> and TSH remain normal.</li><li>(4) <i>No</i> signs of hypothyroidism
<blockquote style="color: blue; ">Alterations in TBG: alter total serum T<sub>4</sub>; no effect on FT<sub>4</sub> and TSH</blockquote></li> </ul><li>Normal TBG with increase or decrease in total serum T<sub>4</sub></li><ul> <li>(1) Increase or decrease in FT<sub>4</sub> must be present.</li><li>(2) Increased FT<sub>4</sub>-Graves' disease, thyroiditis</li><li>(3) Decreased FT<sub>4</sub>-hypothyroidism</li> </ul> </ol><li>Serum TSH</li><ol type="a"> <li>Best overall screening test for thyroid dysfunction
<blockquote style="color: blue; ">Serum TSH: best screening test for thyroid dysfunction</blockquote></li><li>Increased TSH</li><ul> <li>Primary hypothyroidism</li> </ul><li>Decreased TSH</li><ul> <li>(1) Thyrotoxicosis (e.g., Graves' disease)</li><li>(2) Hypopituitarism/hypothalamic dysfunction</li><ul> <li>Causes secondary/tertiary hypothyroidism, respectively</li> </ul> </ul> </ol><li><sup>131</sup>I radioactive uptake</li><ol type="a"> <li>Evaluates synthetic activity of the thyroid gland
<blockquote style="color: blue; "><sup>131</sup>I uptake: evaluates synthetic activity of thyroid gland</blockquote></li><ul> <li>Iodide is used to synthesize thyroid hormone.</li> </ul><li>Increased uptake indicates increased synthesis of T<sub>4</sub>.</li><ul> <li>Examples-Graves' disease, toxic nodular goiter
<blockquote style="color: blue; ">↑ <sup>131</sup>I uptake: increased synthesis of thyroid hormone; Graves' disease</blockquote></li> </ul><li>Decreased uptake of <sup>131</sup>I</li><ul> <li>(1) Inactivity of the gland</li><ul> <li>Example-patient taking thyroid hormone</li> </ul><li>(2) Inflammation of the gland</li><ul> <li>Example-acute/subacute/chronic thyroiditis
<blockquote style="color: blue; ">↓ <sup>131</sup>I uptake: thyroiditis; patient taking excess thyroid hormone</blockquote></li> </ul> </ul><li>Evaluates functional status of thyroid nodules</li><ul> <li>(1) Decreased uptake in a nodule</li><ul> <li>"Cold" nodule-cyst, adenoma, cancer (<span>[[Fig. 22-5|Figure 22-5]]</span>)
<blockquote style="color: blue; ">Cold nodule: ↓ <sup>131</sup>I uptake</blockquote></li> </ul><li>(2) Increased uptake in a nodule</li><ul> <li>"Hot" nodule-toxic nodular goiter
<blockquote style="color: blue; ">Hot nodule: ↑ <sup>131</sup>I uptake</blockquote></li> </ul> </ul> </ol><li>Thyroglobulin</li><ul> <li>Marker for thyroid cancer</li> </ul> </ol>
</div></html>
<html><a name="HC022021"></a> <br><a name="P022019"></a><div class="PA" style="color: black; "><ol type="1"> <li>Failed descent of thyroid anlage from the base of the tongue
<blockquote style="color: blue; ">Mass at base of the tongue: lingual thyroid</blockquote></li><ul> <li>Usually represents all of the thyroid tissue</li> </ul><li>Clinical findings</li><ol type="a"> <li>Dysphagia for solids</li><li>Mass lesion</li> </ol><li><sup>131</sup>I scan locates the lesion</li><ul> <li>Also identifies any other thyroid tissue that is present</li> </ul><li>Treatment</li><ol type="a"> <li>Suppression with thyroxine</li><ul> <li>Lingual thyroids are usually hypofunctional.</li> </ul><li>Ablation with radioactive iodine</li><li>Surgery if obstructive</li> </ol> </ol>
</div></html>
<html><a name="HC022022"></a> <br><a name="P022020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Cystic midline mass that is close to or within the hyoid bone (<span>[[Fig. 22-6|Figure 22-6]]</span>)
<blockquote style="color: blue; ">Thyroglossal duct cyst: cystic midline mass</blockquote></li><li>Surgery with removal of the proximal duct and hyoid bone</li> </ol>
</div></html>
<html><a name="HC022023"></a> <br><a name="P022021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acute thyroiditis
<blockquote style="color: blue; ">Branchial cleft cyst: located in the anterolateral neck</blockquote></li><ol type="a"> <li>Bacterial infection (e.g., <i>Staphylococcus aureus</i>)</li><li>Clinical findings</li><ul> <li>(1) Fever</li><li>(2) Tender gland with painful cervical adenopathy
<blockquote style="color: blue; ">Acute thyroiditis: thyrotoxicosis; ↓ <sup>131</sup>I uptake</blockquote></li><li>(3) Initial thyrotoxicosis from gland destruction</li><ul> <li>Increased serum T<sub>4</sub>, decreased serum TSH</li> </ul><li>(4) Permanent hypothyroidism is uncommon.</li> </ul><li>Decreased <sup>131</sup>I uptake</li><li>Treatment</li><ul> <li>Penicillin or ampicillin</li> </ul> </ol><li>Subacute granulomatous thyroiditis</li><ol type="a"> <li>Viral infection (e.g., coxsackievirus, mumps)</li><li>Occurs most often in women 40 to 50 years old</li><li>Granulomatous inflammation with multinucleated giant cells</li><li>Clinical findings</li><ul> <li>(1) Most common cause of a painful thyroid gland
<blockquote style="color: blue; ">Subacute granulomatous thyroiditis: most common cause of painful thyroid; virus induced; no adenopathy</blockquote></li><li>(2) Often preceded by an upper respiratory infection</li><li>(3) Cervical adenopathy is <i>not</i> prominent.</li><li>(4) Initial thyrotoxicosis from gland destruction</li><ul> <li>Increased serum T<sub>4</sub>, decreased serum TSH</li> </ul><li>(5) Permanent hypothyroidism is uncommon.</li> </ul><li>Decreased <sup>131</sup>I uptake</li><li>Self-limited; does <i>not</i> require treatment</li> </ol><li>Hashimoto's thyroiditis</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Autoimmune thyroiditis
<blockquote style="color: blue; ">Hashimoto's thyroiditis: autoimmune thyroiditis</blockquote></li><li>(2) Incidence increases with age</li><li>(3) More common in women than men</li><li>(4) Human leukocyte antigen (HLA)-Dr3 and -Dr5 associations</li><li>(5) Increased incidence in:</li><ul> <li>Turner's syndrome, Down syndrome, Klinefelter's syndrome</li> </ul><li>(6) Increased incidence of other autoimmune diseases (e.g., pernicious anemia)</li> </ul><li>Pathogenesis</li><ul> <li>(1) Cytotoxic T cells destroy parenchyma (type IV hypersensitivity).</li><ul> <li>Initial thyrotoxicosis, eventual hypothyroidism</li> </ul><li>(2) Blocking IgG autoantibodies against the TSH receptor</li><ul> <li>Decrease hormone synthesis; type II hypersensitivity
<blockquote style="color: blue; ">Hashimoto's thyroiditis: type IV (mainly) and type II hypersensitivity</blockquote></li> </ul><li>(3) Antimicrosomal and thyroglobulin antibodies</li><ul> <li>Develop as a <i>result</i> of gland injury; no causal role</li> </ul> </ul><li>Gross and microscopic</li><ul> <li>(1) Enlarged, gray gland</li><li>(2) Lymphocytic infiltrate with prominent germinal follicles (<span>[[Fig. 22-7|Figure 22-7]]</span>)</li> </ul><li>Clinical findings</li><ul> <li>(1) Most common cause of primary hypothyroidism
<blockquote style="color: blue; ">Hashimoto's thyroiditis: most common cause of hypothyroidism</blockquote></li><li>(2) Initial thyrotoxicosis from gland destruction</li><ul> <li>Known as <i>hashitoxicosis</i></li> </ul><li>(3) Signs of hypothyroidism (see later discussion)</li><li>(4) Risk factor for primary B-cell malignant lymphoma of the thyroid</li> </ul> </ol><li>Reidel's thyroiditis</li><ol type="a"> <li>Fibrous tissue replacement of the gland</li><li>Extension of fibrosis into surrounding tissue
<blockquote style="color: blue; ">Reidel's thyroiditis: fibrous tissue replacement of gland and surrounding tissue</blockquote></li><ul> <li>Can produce tracheal obstruction</li> </ul><li>Associated with other sclerosing conditions</li><ul> <li>Example-sclerosing mediastinitis</li> </ul><li>Hypothyroidism may occur.</li><li>Treatment</li><ul> <li>(1) Initial treatment with corticosteroids</li><li>(2) Tamoxifen</li><ul> <li>First-line therapy or if corticosteroids are unsuccessful
<blockquote style="color: blue; ">Subacute painless lymphocytic thyroiditis: develops post partum; progression to hypothyroidism</blockquote></li> </ul><li>(3) Surgery</li> </ul> </ol><li>Subacute painless lymphocytic thyroiditis</li><ol type="a"> <li>Autoimmune disease that develops post partum</li><li>Gland lacks germinal follicles.</li><li>Clinical findings</li><ul> <li>(1) Abrupt onset of thyrotoxicosis due to gland destruction</li><li>(2) Gland is slightly enlarged and painless.</li><li>(3) Progresses to primary hypothyroidism in 40% to 50% of cases</li><li>(4) Antimicrosomal antibodies (50-80%)</li> </ul><li>Treatment</li><ul> <li>Levothyroxine in the hypothyroid stage</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC022024"></a> <br><a name="P022022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Reduced secretion of thyroid hormone
<blockquote style="color: blue; ">Hypothyroidism: hypometabolic</blockquote></li><ol type="a"> <li>Patients are hypometabolic.</li><li>Decrease in the basal metabolic rate</li> </ol><li>Causes</li><ol type="a"> <li>Hashimoto's thyroiditis (90% of cases)</li><li>Subacute painless lymphocytic thyroiditis</li><li>Hypopituitarism, iodine deficiency, enzyme deficiency</li><li>Drugs</li><ul> <li>Amiodarone, lithium, sulfonamides, phenylbutazone</li> </ul><li>Hypothalamic dysfunction/hypopituitarism (see sections II and IV, respectively)</li><li>Congenital (see later discussion)</li> </ol><li>Cretinism</li><ol type="a"> <li>Hypothyroidism in infancy or early childhood
<blockquote style="color: blue; ">Brain: requires thyroxine for maturation</blockquote></li><li>Brain requires thyroxine for its maturation.</li><li>Causes</li><ul> <li>(1) Maternal hypothyroidism
<blockquote style="color: blue; ">Cretinism: most often caused by maternal hypothyroidism before fetal thyroid is developed</blockquote></li><ul> <li><i>Before</i> the fetal thyroid is developed</li> </ul><li>(2) Enzyme or iodine deficiency</li> </ul><li>Clinical findings</li><ul> <li>(1) Severe mental retardation</li><li>(2) Increased weight and short stature
<blockquote style="color: blue; ">Cretinism: severe mental retardation</blockquote></li><ul> <li>Pituitary dwarfism-decreased weight and short stature</li> </ul> </ul><li>Treatment is thyroid hormone replacement.</li> </ol><li>Clinical findings in adult hypothyroidism</li><ol type="a"> <li>Proximal muscle myopathy</li><ul> <li>(1) Very common finding</li><li>(2) Increased serum creatine kinase
<blockquote style="color: blue; ">Hashimoto's thyroiditis: muscle weakness common complaint; weight gain; dry, brittle hair</blockquote></li> </ul><li>Weight gain</li><ul> <li>Due to hypometabolic state with retention of water and salt</li> </ul><li>Dry and brittle hair; loss of outer one-third of eyebrow</li><li>Bradycardia (slow heart rate)</li><li>Coarse yellow skin</li><ul> <li>Yellow skin due to less conversion of β-carotenes into retinoic acid</li> </ul><li>Periorbital puffiness, hoarse voice
<blockquote style="color: blue; ">Hashimoto's thyroiditis: periorbital puffiness, hoarse voice; signs of myxedema</blockquote></li><ul> <li>(1) Both of these are due to myxedema (<span>[[Fig. 22-8|Figure 22-8]]</span>)</li><li>(2) Increased hyaluronic acid and chondroitin sulfate in interstitial tissue</li><li>(3) Nonpitting edema</li> </ul><li>Fatigue, cold intolerance, constipation
<blockquote style="color: blue; ">Hashimoto's thyroiditis: cold intolerance, constipation</blockquote></li><li>Menstrual irregularities</li><ul> <li>Most often menorrhagia</li> </ul><li>Diastolic hypertension</li><ul> <li>Due to retention of sodium and water
<blockquote style="color: blue; ">Hashimoto's thyroiditis: hypertension from sodium retention; delayed reflexes</blockquote></li> </ul><li>Congestive (dilated) cardiomyopathy with biventricular heart failure</li><li>Atherosclerotic coronary artery disease</li><li>Delayed recovery of Achilles reflex, mental slowness, dementia</li> </ol><li>Laboratory findings</li><ol type="a"> <li>Decreased serum T<sub>4</sub>, increased serum TSH
<blockquote style="color: blue; ">Primary hypothyroidism: ↓ serum T<sub>4</sub>/FT<sub>4</sub>; ↑ serum TSH, cholesterol</blockquote></li><li>Antimicrosomal, antiperoxidase, and antithyroglobulin antibodies</li><ul> <li>Present in Hashimoto's thyroiditis</li> </ul><li>Hypercholesterolemia</li><ul> <li>Due to decreased synthesis of low-density lipoprotein (LDL) receptors</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Levothyroxine in small increments every 6-8 weeks</li><li>Bring serum TSH into the normal range (euthyroid state)</li> </ol><li>Myxedema coma</li><ol type="a"> <li>Causes</li><ul> <li>(1) Idiopathic; cold exposure</li><li>(2) Use of sedatives/opiates</li><li>(3) Acute illness</li> </ul><li>Clinical findings
<blockquote style="color: blue; ">Myxedema coma: stupor, hypothermia, hypoventilation; IV levothyroxine, corticosteroids</blockquote></li><ul> <li>(1) Progressive stupor</li><li>(2) Hypothermia</li><li>(3) Bradycardia; hypoventilation</li><li>(4) Hypoglycemia, hypocortisolism, SIADH</li> </ul><li>Treatment</li><ul> <li>(1) Ventilatory support</li><li>(2) Treat hypothermia</li><li>(3) IV levothyroxine</li><li>(4) High doses of corticosteroids</li> </ul><li>Mortality rate is 20% to 50%.</li> </ol> </ol>
</div></html>
<html><a name="HC022025"></a> <br><a name="P022023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Classification</li><ol type="a"> <li>Thyrotoxicosis</li><ul> <li>Describes hormone excess regardless of cause
<blockquote style="color: blue; ">Thyrotoxicosis: hormone excess from any cause</blockquote></li> </ul><li>Hyperthyroidism</li><ul> <li>(1) Describes hormone excess due to increased synthesis
<blockquote style="color: blue; ">Hyperthyroidism: thyrotoxicosis due to excess synthesis of thyroid hormone</blockquote></li><li>(2) Examples-Graves' disease, toxic nodular goiter</li> </ul> </ol><li>Patients are hypermetabolic.</li><ul> <li>Increase in the basal metabolic rate
<blockquote style="color: blue; ">Graves' disease: most common cause of hyperthyroidism and thyrotoxicosis</blockquote></li> </ul><li>Graves' disease</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Most common cause of hyperthyroidism and thyrotoxicosis</li><li>(2) Female dominant autoimmune disease</li><li>(3) HLA-B8 and HLA-Dr3 association</li> </ul><li>Pathogenesis</li><ul> <li>(1) T cells induce specific B cells to produce IgG antibodies against the TSH-receptor</li><ul> <li>(a) Stimulating type of antibody as opposed to a blocking antibody
<blockquote style="color: blue; ">Graves' disease: anti-TSH receptor antibody, type II hypersensitivity</blockquote></li><li>(b) Type II hypersensitivity reaction</li> </ul><li>(2) Antimicrosomal and thyroglobulin antibodies are present.</li><li>(3) Inciting events that may initiate onset of the disease</li><ul> <li>Infection, withdrawal of steroids, iodide excess, post partum</li> </ul> </ul><li>Symmetrical, nontender thyromegaly</li><ul> <li>(1) Scant colloid</li><li>(2) Papillary infolding of the glands</li> </ul><li>Clinical features unique to Graves' disease
<blockquote style="color: blue; ">Unique to Graves': exophthalmos, pretibial myxedema, thyroid acropachy</blockquote></li><ul> <li>(1) Infiltrative ophthalmopathy (exophthalmos; 50%)</li><ul> <li>(a) Proptosis and muscle weakness of the eye (<span>[[Figs. 22-9|Figure 22-9]]</span> and <span>[[22-10|Figure 22-10]]</span>)</li><li>(b) Due to adipose and glycosaminoglycans deposited in orbital tissue
<blockquote style="color: blue; ">Transient hyperthyroidism in fetus</blockquote></li><li>(c) IgG-TSH receptor antibodies can cross placenta and produce transient hyperthyroidism in fetus</li> </ul><li>(2) Pretibial myxedema (1-2%; <span>[[Fig. 22-11|Figure 22-11]]</span>)</li><ul> <li>Due to excess glycosaminoglycans in the dermis</li> </ul><li>(3) Thyroid acropachy</li><ul> <li>(a) Digital swelling and clubbing of fingers</li><li>(b) Nails separate from nail bed (lifted up)</li><li>(c) Exophthalmos and pretibial myxedema usually present
<blockquote style="color: blue; ">Thyroid acropathy: digital swelling and clubbing</blockquote></li> </ul> </ul> </ol><li>Graves' disease in the elderly (apathetic hyperthyroidism)</li><ol type="a"> <li>Cardiac abnormalities</li><ul> <li>Atrial fibrillation, congestive heart failure
<blockquote style="color: blue; ">Graves' disease in elderly: cardiac and muscle findings predominate; apathetic appearing</blockquote></li> </ul><li>Muscle weakness, apathy</li><li>Thyromegaly</li> </ol><li>Toxic multinodular goiter (Plummer's disease)
<blockquote style="color: blue; ">Toxic multinodular goiter: one or more nodules in a multinodular goiter becomes TSH-independent</blockquote></li><ol type="a"> <li>One or more nodules in a multinodular goiter become TSH-independent.</li><li>See "hot" nodules with <sup>131</sup>I scan</li><li>Distinctions from Graves' disease</li><ul> <li><i>Lack</i> exophthalmos and pretibial myxedema</li> </ul><li>Treatment is surgery.</li> </ol><li>Clinical findings in all causes of thyrotoxicosis</li><ol type="a"> <li>Constitutional signs</li><ul> <li>(1) Weight loss (good appetite)</li><li>(2) Fine tremor of the hands
<blockquote style="color: blue; ">Thyrotoxicosis: weight loss with a good appetite; heat intolerance; diarrhea</blockquote></li><li>(3) Heat intolerance, diarrhea, anxiety</li><li>(4) Menstrual irregularities</li><ul> <li>Usually oligomenorrhea
<blockquote style="color: blue; ">Thyrotoxicosis: oligomenorrhea; lid stare; sinus tachycardia; systolic hypertension; brisk reflexes</blockquote></li> </ul><li>(5) Lid stare</li><ul> <li>Due to increased sympathetic stimulation of eyelid muscles</li> </ul> </ul><li>Cardiac findings</li><ul> <li>(1) Sinus tachycardia (>90 beats/min)</li><li>(2) Increased risk for atrial fibrillation
<blockquote style="color: blue; ">Atrial fibrillation: always order a TSH test to rule out hyperthyroidism</blockquote></li><li>(3) Systolic hypertension, high-output heart failure</li><ul> <li>(a) Thyroid hormone increases β-receptor synthesis in the heart.</li><li>(b) Excess hormone increases inotropic and chronotropic effect on the heart.</li> </ul> </ul><li>Brisk reflexes, osteoporosis (increased bone turnover)</li> </ol><li>Laboratory findings</li><ol type="a"> <li>Increased serum T<sub>4</sub>, decreased serum TSH
<blockquote style="color: blue; ">Graves' hyperthyroidism: ↑ serum T<sub>4</sub>/FT<sub>4</sub>, ↑ <sup>131</sup>I uptake, ↓ serum TSH</blockquote></li><li>Increased <sup>131</sup>I uptake</li><ul> <li>Graves' disease and toxic multinodular goiter</li> </ul><li>Decreased <sup>131</sup>I uptake</li><ul> <li>Thyroiditis, patient taking excess thyroid hormone
<blockquote style="color: blue; ">Thyrotoxicosis: ↑ glucose, calcium, lymphocytes; ↓ cholesterol</blockquote></li> </ul><li>Hyperglycemia</li><ul> <li>Increased glycogenolysis</li> </ul><li>Hypocholesterolemia</li><ul> <li>Increased LDL receptor synthesis</li> </ul><li>Hypercalcemia</li><ul> <li>Increased bone turnover</li> </ul><li>Absolute lymphocytosis</li> </ol><li>Treatment of Graves' disease
<blockquote style="color: blue; ">Treatment for Graves' disease: β-blockers, thionamides</blockquote></li><ol type="a"> <li>β-Blockers decrease adrenergic effects.</li><li>Thionamides decrease hormone synthesis.</li><li>Ablative <sup>131</sup>I therapy in 1 year if above regimen does not work</li> </ol><li>Thyroid storm</li><ol type="a"> <li>Causes</li><ul> <li>(1) Inadequately treated patients with Graves' disease undergo surgery.</li><li>(2) Infection; trauma</li><li>(3) Iodine; pregnancy</li> </ul><li>Clinical findings
<blockquote style="color: blue; ">Thyroid storm: tachyarrhythmias, hyperpyrexia, coma, shock</blockquote></li><ul> <li>(1) Tachyarrhythmias</li><li>(2) Hyperpyrexia</li><li>(3) Shock</li><ul> <li>Volume depletion from vomiting</li> </ul><li>(4) Coma</li> </ul><li>Treatment</li><ul> <li>(1) Inhibit hormone synthesis</li><ul> <li>(a) Propylthiouracil</li><li>(b) Iodide</li> </ul><li>(2) Sympathetic blockade with β-blockers</li><li>(3) Hydrocortisone</li><li>(4) Cooling blanket</li> </ul> </ol><li>Euthyroid sick syndrome (ESS)</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Abnormalities in serum T<sub>3</sub> and T<sub>4</sub> but gland function appears normal
<blockquote style="color: blue; ">ESS: serum T<sub>3</sub> and T<sub>4</sub> abnormalities; normal gland function</blockquote></li><li>(2) Associated with:</li><ul> <li>Malignancy, heart failure, chronic renal failure, sepsis, myocardial infarction</li> </ul><li>(3) Laboratory test alterations usually return to normal with resolution of the illness.</li> </ul><li>Pathogenesis</li><ul> <li>(1) Normally, a peripheral tissue outer ring deiodinase converts T<sub>4</sub> into metabolically active T<sub>3</sub>.</li><li>(2) In ESS, outer ring deiodinase is blocked and inner ring deiodinase converts T<sub>4</sub> into inactive reverse T<sub>3</sub>.
<blockquote style="color: blue; ">ESS: block in outer ring deiodinase conversion of T<sub>4</sub> to T<sub>3</sub>; T<sub>4</sub> converted to inactive reverse T<sub>3</sub></blockquote></li><ul> <li>There are also abnormalities in thyroid-binding globulin.</li> </ul><li>(3) Most common variant of ESS</li><ul> <li>(a) Normal/decreased serum T<sub>4</sub>
<blockquote style="color: blue; ">ESS: ↓ serum T<sub>3</sub> and ↑ reverse T<sub>3</sub></blockquote></li><li>(b) Decreased serum T<sub>3</sub></li><li>(c) Normal/decreased serum TSH</li><li>(d) Increased serum reverse T<sub>3</sub></li> </ul> </ul><li>Treatment</li><ul> <li>Varies from no treatment to levothyroxine during the time of the illness</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC022026"></a><span>[[Table 22-2|Table 22-2. LABORATORY FINDINGS IN THYROID DISEASE]]</span> <br> <br> </html>
<html><a name="HC022027"></a> <br><a name="P022024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Thyroid enlargement from excess colloid (<span>[[Fig. 22-12|Figure 22-12]]</span>)
<blockquote style="color: blue; ">Goiter: thyroid enlargement</blockquote></li><li>Types of goiter</li><ol type="a"> <li>Endemic type</li><ul> <li>Due to iodide deficiency (most common)</li> </ul><li>Sporadic type; causes include:</li><ul> <li>Goitrogens (e.g., cabbage), enzyme deficiency, puberty, pregnancy</li> </ul> </ol><li>Pathogenesis
<blockquote style="color: blue; ">Nontoxic goiter: absolute or relative deficiency of thyroid hormone</blockquote></li><ol type="a"> <li>Absolute or relative deficiency of thyroid hormone</li><li>Hyperplasia/hypertrophy</li><ul> <li>Attempt to increase hormone synthesis</li> </ul><li>Hyperplasia/hypertrophy is followed by gland involution.
<blockquote style="color: blue; ">Nontoxic goiter: hyperplasia/hypertrophy followed by involution; initially diffuse then nodular</blockquote></li><ul> <li>Failure of gland to sustain synthesis</li> </ul><li>Initial diffuse thyromegaly is followed by multinodular goiter (<span>[[Fig. 22-13|Figure 22-13]]</span>)</li> </ol><li>Complications</li><ol type="a"> <li>Hemorrhage into cyst</li><ul> <li>Produces sudden, painful, gland enlargement</li> </ul><li>Compression of jugular vein causing neck congestion</li><ul> <li>Called Pemberton's sign</li> </ul><li>Primary hypothyroidism</li><li>Toxic nodular goiter
<blockquote style="color: blue; ">Toxic nodular goiter: one or more nodules become TSH-independent</blockquote></li><ul> <li>One or more nodules become TSH-independent; "hot" nodule.</li> </ul><li>Hoarseness (compresses laryngeal nerve)</li><li>Dyspnea (compresses trachea)</li> </ol><li>Treatment</li><ol type="a"> <li>Levothyroxine reduces gland size and achieves the euthyroid state.</li><li>Surgery if compressive symptoms persist</li> </ol> </ol>
</div></html>
<html><a name="HC022028"></a> <br><a name="P022025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Majority are cold nodules (95%).</li><li>Causes in adult women
<blockquote style="color: blue; ">Solitary nodule in a woman: majority are benign; 15% malignant</blockquote></li><ul> <li>(1) Majority are cysts in a goiter (60%) or a follicular adenoma (25%).</li><li>(2) Approximately 15% are malignant.</li><li>(3) Approximately 85% to 90% of solitary nodules are euthyroid.
<blockquote style="color: blue; ">Solitary nodule in man/child: more likely to be malignant</blockquote></li> </ul><li>Causes in adult men and children</li><ul> <li>Similar to women, but there is a greater chance of malignancy</li> </ul><li>Prior history of radiation to head and neck
<blockquote style="color: blue; ">Solitary nodule with history of radiation exposure: more likely to be malignant (40%)</blockquote></li><ul> <li>Nodule is more likely to be malignant (40% of cases).</li> </ul> </ol><li>Diagnosis</li><ol type="a"> <li>Fine needle aspiration (FNA) most important initial step
<blockquote style="color: blue; ">First step in management of solitary thyroid nodule: fine needle aspiration</blockquote></li><li>Thyroid hormone studies</li> </ol><li>Treatment</li><ol type="a"> <li>Depends on the FNA result</li><li>If malignant, surgical removal</li><li>If benign and asymptomatic, periodic follow-up</li> </ol> </ol>
</div></html>
<html><a name="HC022029"></a> <br><a name="P022026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Follicular adenoma
<blockquote style="color: blue; ">Follicular adenoma: most common benign thyroid tumor</blockquote></li><ol type="a"> <li>Most common benign tumor</li><ul> <li>Surrounded by a complete capsule</li> </ul><li>Presents as a solitary "cold" nodule (see <span>[[Fig. 22-5|Figure 22-5]]</span>)</li><li>Approximately 10% progress into a follicular carcinoma.</li> </ol><li>Papillary adenocarcinoma</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Most common endocrine cancer</li><li>(2) Papillary adenocarcinoma most common thyroid cancer (>75%)</li><li>(3) More common in women than men (3:1)</li><ul> <li>Usually occur in second and third decades
<blockquote style="color: blue; ">Papillary carcinoma: most common endocrine cancer</blockquote></li> </ul><li>(4) Associated with radiation exposure</li> </ul><li>Gross and microscopic findings</li><ul> <li>(1) Usually multifocal</li><li>(2) Papillary fronds intermixed with follicles
<blockquote style="color: blue; ">Papillary carcinoma: most common thyroid cancer; psammoma bodies</blockquote></li><li>(3) Psammoma bodies (35-45% of cases)</li><ul> <li>Dystrophically calcified cancer cells (<span>[[Fig. 22-14|Figure 22-14]]</span>)</li> </ul><li>(4) Empty-appearing nuclei</li><ul> <li>Called Orphan Annie nuclei</li> </ul><li>(5) Lymphatic invasion
<blockquote style="color: blue; ">Papillary carcinoma: lymphatic invasion</blockquote></li> </ul><li>Metastasize to cervical nodes, lung</li><li>Diagnose with FNA</li><li>Treatment</li><ul> <li>(1) Usually subtotal or near total thyroidectomy with sampling of cervical nodes</li><li>(2) Followed in a few weeks by radiotherapy with <sup>131</sup>I</li><li>(3) Suppressive therapy with thyroid hormone</li><ul> <li>Tumor is TSH dependent.</li> </ul> </ul><li>Five-year survival rate > 95%</li> </ol><li>Follicular carcinoma
<blockquote style="color: blue; ">Follicular carcinoma: most common thyroid cancer presenting as a solitary cold nodule</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Most common thyroid cancer presenting as a solitary cold nodule</li><li>(2) Female dominant cancer</li> </ul><li>Gross and microscopic findings</li><ul> <li>(1) Encapsulated or invasive</li><li>(2) Neoplastic follicles invade blood vessels.
<blockquote style="color: blue; ">Follicular carcinoma: hematogenous rather than lymphatic spread</blockquote></li><li>(3) Lymph node metastasis is uncommon.</li> </ul><li>Metastasize to lung and bone</li><li>Treatment</li><ul> <li>Similar to papillary cancer</li> </ul><li>Five-year survival rate ∼80%.</li> </ol><li>Medullary carcinoma</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Types</li><ul> <li>(a) Sporadic (80% of cases)</li><li>(b) Familial (20% of cases)</li> </ul><li>(2) Familial type</li><ul> <li>(a) Associated with autosomal dominant MEN IIa/IIb</li><li>(b) MEN IIa syndrome
<blockquote style="color: blue; ">MEN IIa: medullary carcinoma, HPTH, pheochromocytoma</blockquote></li><ul> <li>Medullary carcinoma, hyperparathyroidism (HPTH), pheochromocytoma</li> </ul><li>(c) MEN IIb (III) syndrome</li><ul> <li>Medullary carcinoma, mucosal neuromas (lips/tongue), pheochromocytoma
<blockquote style="color: blue; ">MEN IIb (III): medullary carcinoma, mucosal neuromas lips/tongue, pheochromocytoma</blockquote></li> </ul> </ul><li>(3) Familial type has a better prognosis than sporadic type.</li><li>(4) Ectopic hormones</li><ul> <li>ACTH, which can produce Cushing syndrome</li> </ul> </ul><li>Pathogenesis</li><ul> <li>(1) Tumors derive from parafollicular C cells.
<blockquote style="color: blue; ">Medullary carcinoma: derives from C cells; calcitonin is tumor marker</blockquote></li><li>(2) C cells synthesize calcitonin.</li><ul> <li>(a) Tumor marker</li><li>(b) May produce hypocalcemia
<blockquote style="color: blue; ">Medullary carcinoma: calcitonin converted into amyloid</blockquote></li><li>(c) Converted into amyloid</li> </ul><li>(3) C-cell hyperplasia is a precursor lesion.</li><ul> <li>Calcitonin levels increase with infusion of pentagastrin.</li> </ul> </ul><li>Diagnosis</li><ul> <li>(1) FNA</li><li>(2) Serum calcitonin</li> </ul><li>Treatment</li><ul> <li>(1) Total thyroidectomy</li><li>(2) Genetic screening for familial cases</li><ul> <li>(a) Detection of mutation of <i>RET</i> proto-oncogene</li><li>(b) Thyroidectomy is performed if patient is a gene carrier.</li> </ul> </ul> </ol><li>Primary B-cell malignant lymphoma
<blockquote style="color: blue; ">Primary B-cell lymphoma: most often derives from Hashimoto's thyroiditis</blockquote></li><ul> <li>Most often develop from Hashimoto's thyroiditis</li> </ul><li>Anaplastic thyroid cancer</li><ol type="a"> <li>Most often occurs in elderly women</li><li>Risk factors</li><ul> <li>Multinodular goiter, history of follicular cancer</li> </ul><li>Rapidly aggressive and uniformly fatal
<blockquote style="color: blue; ">Anaplastic thyroid cancer: rapidly aggressive; uniformally fatal</blockquote></li><li>Treatment</li><ul> <li>(1) Palliative surgery; often compresses trachea</li><li>(2) Irradiation or chemotherapy</li> </ul><li>Five-year survival rate is 5%.</li> </ol> </ol>
</div></html>
![[22.V.A.Steps in thyroid hormone synthesis]]
<<tiddler [[22.V.A.Steps in thyroid hormone synthesis]]>>
![[22.V.B.Functions of thyroid hormone]]
<<tiddler [[22.V.B.Functions of thyroid hormone]]>>
![[22.V.C.Thyroid function tests]]
<<tiddler [[22.V.C.Thyroid function tests]]>>
![[22.V.D.Lingual thyroid]]
<<tiddler [[22.V.D.Lingual thyroid]]>>
![[22.V.E.Thyroglossal duct cyst]]
<<tiddler [[22.V.E.Thyroglossal duct cyst]]>>
![[22.V.F.Thyroiditis]]
<<tiddler [[22.V.F.Thyroiditis]]>>
![[22.V.G.Hypothyroidism]]
<<tiddler [[22.V.G.Hypothyroidism]]>>
![[22.V.H.Thyroid hormone excess]]
<<tiddler [[22.V.H.Thyroid hormone excess]]>>
![[22.V.I.Summary of laboratory findings in thyroid disorders (Table 22-2)]]
<<tiddler [[22.V.I.Summary of laboratory findings in thyroid disorders (Table 22-2)]]>>
![[22.V.J.Nontoxic goiter]]
<<tiddler [[22.V.J.Nontoxic goiter]]>>
![[22.V.K.Solitary thyroid nodule]]
<<tiddler [[22.V.K.Solitary thyroid nodule]]>>
![[22.V.L.Benign and malignant tumors]]
<<tiddler [[22.V.L.Benign and malignant tumors]]>>
<html><a name="HC022031"></a> <br><a name="P022038"></a><div class="PA" style="color: black; "><ol type="1"> <li>Superior and inferior parathyroid glands
<blockquote style="color: blue; ">Superior and inferior parathyroids: derive from 4th and 3rd pharyngeal pouch, respectively</blockquote></li><ul> <li>Derive from fourth pharyngeal pouch and third pharyngeal pouch, respectively</li> </ul><li>PTH</li><ol type="a"> <li>Increases calcium reabsorption in the early distal tubule</li><li>Decreases bicarbonate reclamation in the proximal tubule
<blockquote style="color: blue; ">PTH: ↑ renal calcium reabsorption; ↓ renal phosphorus, bicarbonate reabsorption</blockquote></li><li>Decreases phosphorus reabsorption in the proximal tubule</li><li>Maintains ionized calcium level in blood</li><ul> <li>Increases bone resorption and renal reabsorption of calcium</li> </ul><li>Increases synthesis of 1-α-hydroxylase in proximal renal tubule
<blockquote style="color: blue; ">PTH: hypocalcemia/hyperphosphatemia ↑ PTH; hypercalcemia/hypophosphatemia ↓ PTH</blockquote></li><ul> <li>(1) Increases synthesis of 1, 25-(OH)<sub>2</sub>D (dihydroxycholecalciferol; calcitriol)</li><li>(2) Inhibits 24-hydroxylase in proximal tubule, which normally converts 25-hydroxycholecalciferol synthesized in the liver to inactive 24,25-(OH)<sub>2</sub>D.</li> </ul><li>Stimulated by hypocalcemia and hyperphosphatemia</li><li>Suppressed by hypercalcemia and hypophosphatemia</li> </ol><li>Role of vitamin D in calcium metabolism (see <span>[[Fig. 7-3|Figure 7-3]]</span>)</li><ol type="a"> <li>Preformed vitamin D in the diet consists of cholecalciferol (fish) and ergocalciferol (plants).</li><li>Endogenous synthesis of vitamin D in the skin occurs by photoconversion of 7-dehydrocholesterol via sunlight to vitamin D<sub>3</sub> (cholecalciferol).
<blockquote style="color: blue; ">Sunlight: major source of vitamin D</blockquote></li><li>Reabsorption of vitamin D occurs in the small intestine.</li><li>Liver hydroxylation of precursor vitamin D to 25-hydroxyvitamin D (25-(OH)D; calcidiol)</li><ul> <li>Occurs in the cytochrome P-450 system.
<blockquote style="color: blue; ">Liver: 25-hydroxylase converts cholecalciferol to 25-(OH)D (calcidiol)</blockquote></li> </ul><li>25-(OH)D is secreted into the blood and bound to a protein for delivery to the proximal tubules of the kidneys.</li><li>Kidney hydroxylation of 25-(OH)D by 1α-hydroxylase produces 1,25-(OH)<sub>2</sub>-D (active form of vitamin D; calcitriol).
<blockquote style="color: blue; ">Kidney: 1α-hydroxylase converts 25-(OH)D to 1,25-(OH)<sub>2</sub>D (calcitriol)</blockquote></li><ul> <li>If PTH is decreased, 1α-hydroxylase is decreased, and 24-hydroxylase in the proximal tubule converts 25-(OH)D to metabolically inactive 24,25-(OH)<sub>2</sub>D.</li> </ul><li>Calcitriol attaches to nuclear receptors in target tissues.</li><li>Functions of calcitriol</li><ul> <li>(1) Increased calcium reabsorption in duodenum
<blockquote style="color: blue; ">Calcitriol: ↑ calcium/phosphorus reabsorption in bowel; ↑ osteoclast production</blockquote></li><li>(2) Increased phosphorus reabsorption in jejunum and ileum</li><li>(3) Increases bone resorption</li><ul> <li>Induces monocytic stem cells to become osteoclasts</li> </ul> </ul><li>Feedback control of calcitriol is calcium-mediated.</li><ul> <li>(1) Decreased serum calcium: PTH → synthesis of 1α-hydroxylase → synthesis 1,25-(OH)<sub>2</sub>-D and via inhibition of 24-hydroxylase → ↓ synthesis of metabolically inactive 24,25-(OH)<sub>2</sub>D.
<blockquote style="color: blue; ">Calcitriol feedback: hypocalcemia increases synthesis, hypercalcemia decreases synthesis</blockquote></li><li>(2) Increased serum calcium: ↓ PTH → ↓ synthesis of 1α-hydroxylase → ↓ synthesis 1,25-(OH)<sub>2</sub>-D and via activation of 24-hydroxylase → synthesis of metabolically inactive 24,25-(OH)<sub>2</sub>D.</li> </ul> </ol><li>Total serum calcium
<blockquote style="color: blue; ">Total serum calcium: calcium bound + calcium free (ionized)</blockquote></li><ol type="a"> <li>Components of the total serum calcium (<span>[[Fig. 22-15A|Figure 22-15]]</span>)</li><ul> <li>(1) Calcium bound to albumin (40%) and phosphorus and citrate (13%)</li><ul> <li>(a) Albumin has the most acidic amino acids.</li><li>(b) At a normal pH of 7.4, ∼40% of the acidic groups are COO<sup>-</sup> and can bind to positively charged calcium.</li> </ul><li>(2) Free, ionized calcium (47%)</li><ul> <li>Metabolically active fraction has a negative feedback with PTH.</li> </ul> </ul><li>Hypoalbuminemia (<span>[[Fig. 22-15B|Figure 22-15]]</span>)</li><ul> <li>(1) Decreased total serum calcium</li><ul> <li>Due to a decrease in calcium bound to albumin</li> </ul><li>(2) Normal free ionized level, normal PTH
<blockquote style="color: blue; ">Hypoalbuminemia: ↓ total serum calcium, normal ionized calcium and PTH</blockquote></li><li>(3) <i>No</i> evidence of tetany</li> </ul><li>Effect of respiratory or metabolic alkalosis (<span>[[Fig. 22-15C|Figure 22-15]]</span>)</li><ul> <li>(1) Increases negative charges on albumin</li><ul> <li>(a) Due to fewer hydrogen ions on the COOH groups of acidic amino acids</li><ul> <li>Change of COOH groups to COO<sup>-</sup></li> </ul><li>(b) Extra negative charges bind some of the ionized calcium (arrows in schematic).</li> </ul><li>(2) Total serum calcium remains normal.
<blockquote style="color: blue; ">Alkalosis: normal total serum calcium; decreased ionized calcium, increased PTH; tetany</blockquote></li><li>(3) Decreased ionized calcium, increased PTH</li><li>(4) Patient develops tetany.</li><ul> <li>Although serum PTH is in equilibrium with ionized calcium, it cannot keep pace with the binding of ionized calcium to the negative charges on albumin; hence, tetany occurs.</li> </ul> </ul><li>Tetany is due to a decreased ionized calcium level.</li><ul> <li>(1) Causes partial depolarization of nerves and muscle</li><ul> <li>(a) Lowers the threshold potential (E<sub>t</sub>)</li><ul> <li>Comes closer to the resting membrane potential (E<sub>m</sub>)
<blockquote style="color: blue; ">Tetany: E<sub>t</sub> comes close to E<sub>m</sub>; initiates action potential</blockquote></li> </ul><li>(b) A smaller stimulus is required to initiate an action potential.</li> </ul><li>(2) Clinical findings of tetany</li><ul> <li>(a) Carpopedal spasm</li><ul> <li>Thumb flexes into the palm.
<blockquote style="color: blue; ">Tetany: thumb adduct into palm; facial twitching after tapping facial nerve</blockquote></li> </ul><li>(b) Chvostek's sign</li><ul> <li>Facial twitch after tapping the facial nerve</li> </ul> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC022032"></a> <br><a name="P022039"></a><div class="PA" style="color: black; "><ul> <li>Hypofunction of the parathyroid glands leads to hypocalcemia.
<blockquote style="color: blue; ">Hypoparathyroidism: autoimmune hypoparathyroidism most common cause</blockquote></li><ol type="1"> <li>Causes</li><ol type="a"> <li>Autoimmune hypoparathyroidism (most common cause)</li><li>Previous thyroid surgery</li><ul> <li><i>Not</i> common in current day surgery</li> </ul><li>DiGeorge syndrome
<blockquote style="color: blue; ">DiGeorge syndrome: failure of descent of 3rd/4th pharyngeal pouches; absent parathyroids and thymus</blockquote></li><ul> <li>(1) Failure of descent of third and fourth pharyngeal pouches</li><ul> <li>Absence of parathyroid glands</li> </ul><li>(2) Absent thymus (pure T-cell deficiency)</li> </ul><li>Hypomagnesemia</li><ul> <li>(1) Magnesium is a cofactor for adenylate cyclase.
<blockquote style="color: blue; ">Hypomagnesemia: most common pathologic cause of hypocalcemia in the hospital</blockquote></li><ul> <li>Cyclic adenosine monophosphate (cAMP) is required for PTH activation.</li> </ul><li>(2) Causes of hypomagnesemia</li><ul> <li>Diarrhea, aminoglycosides, diuretics, alcoholism
<blockquote style="color: blue; ">Hypomagnesemia: diarrhea, aminoglycosides, diuretics, alcohol</blockquote></li> </ul> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Tetany</li><li>Calcification of basal ganglia</li><ul> <li>(1) Due to metastatic calcification</li><li>(2) Increased phosphorus drives calcium into the brain tissue.
<blockquote style="color: blue; ">Hypoparathyroidism: ↓ serum calcium, PTH; ↑ serum phosphorus</blockquote></li> </ul><li>Cataracts, <i>Candida</i> infections (? cause)</li> </ol><li>Laboratory findings</li><ul> <li>Hypocalcemia, hyperphosphatemia, decreased PTH</li> </ul><li>Other causes of hypocalcemia (<span>[[Table 22-3|Table 22-3. OTHER CAUSES OF HYPOCALCEMIA]]</span> and <span>[[Fig. 22-16|Figure 22-16]]</span>)</li><li>Treatment</li><ol type="a"> <li>Calcium and vitamin D<sub>3</sub> (calcitriol)
<blockquote style="color: blue; ">Chronic renal failure: most common cause of hypocalcemia; causes hypovitaminosis D</blockquote></li><li>Teriparatide (recombinant PTH) may be used in near future.</li> </ol> </ol> </ul>
</div></html>
<html><a name="HC022033"></a> <br><a name="P022040"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common nonmalignant cause of hypercalcemia</li><li>Occurs most frequently in postmenopausal women</li><li>Asymptomatic in >50% of patients</li><li>Association with MEN I and MEN IIa
<blockquote style="color: blue; ">Primary HPTH: MEN I, IIa association</blockquote></li><li>Causes
<blockquote style="color: blue; ">Most common cause of primary HPTH: benign adenoma</blockquote></li><ul> <li>(1) Adenoma (∼80% of cases; <span>[[Fig. 22-17|Figure 22-17]]</span>)</li><ul> <li>(a) Usually a single adenoma</li><li>(b) Sheets of chief cells with <i>no</i> intervening adipose</li><li>(c) Remainder of the gland plus all other glands show atrophy.</li><ul> <li>Hypercalcemia suppresses PTH produced from normal tissue.</li> </ul><li>(d) Right inferior parathyroid gland is most often involved.</li> </ul><li>(2) Primary hyperplasia (∼20% of cases)</li><ul> <li>(a) All four glands are involved.
<blockquote style="color: blue; ">Primary hyperplasia: all 4 glands involved</blockquote></li><li>(b) Usually a chief cell hyperplasia</li><li>(c) Clear cell hyperplasia (wasserhelle cell hyperplasia)</li><ul> <li>Associated with markedly increased serum calcium levels</li> </ul> </ul><li>(3) Carcinoma (uncommon)</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Renal</li><ul> <li>(1) Calcium stones</li><ul> <li>Most common presentation.
<blockquote style="color: blue; ">Primary HPTH: renal stones most common presentation</blockquote></li> </ul><li>(2) Nephrocalcinosis (refer to <span macro="tag [[01 Cell Injury]] [[Chapters 1]]"></span> and <span macro="tag [[19 Kidney Disorders]] [[19]]"></span>)</li><ul> <li>Causes polyuria and renal failure</li> </ul> </ul><li>Gastrointestinal</li><ul> <li>(1) Peptic ulcer disease (PUD)
<blockquote style="color: blue; ">Primary HPTH: PUD; acute pancreatitis</blockquote></li><ul> <li>Calcium stimulates gastrin, which increases gastric acid.</li> </ul><li>(2) Acute pancreatitis</li><ul> <li>Calcium activates phospholipase.</li> </ul><li>(3) Constipation</li> </ul><li>Bone and joints</li><ul> <li>(1) Osteitis fibrosa cystica
<blockquote style="color: blue; ">Primary HPTH: osteitis fibrosa cystica; subperiosteal bone resorption; osteoporosis; pseudogout</blockquote></li><ul> <li>(a) Cystic and hemorrhagic bone lesion</li><ul> <li>Caused by increased osteoclastic activity</li> </ul><li>(b) Commonly involves the jaw</li> </ul><li>(2) Radiographic findings</li><ul> <li>(a) Subperiosteal bone resorption of phalanges (<span>[[Fig. 22-18|Figure 22-18]]</span>) and tooth sockets</li><li>(b) "Salt and pepper" appearance of the skull</li> </ul><li>(3) Osteoporosis</li><li>(4) Chondrocalcinosis (pseudogout)</li> </ul><li>Diastolic hypertension
<blockquote style="color: blue; ">Primary HPTH: diastolic hypertension</blockquote></li><ul> <li>Due to hypercalcemia</li> </ul><li>Eyes</li><ul> <li>(1) Band keratopathy in the limbus of the eye</li><li>(2) Due to metastatic calcification</li> </ul><li>Central nervous system</li><ul> <li>Myriad of different findings-psychosis, confusion, anxiety, coma
<blockquote style="color: blue; ">Primary HPTH: "stones, bones, abdominal groans, and psychic moans"</blockquote></li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Increased serum PTH, increased calcium, decreased phosphorus
<blockquote style="color: blue; ">Intact serum PTH (iPTH): best initial screen for primary HPTH</blockquote></li><ul> <li>(1) Intact serum PTH is best initial screening test</li><li>(2) Distinguishes it from hypercalcemia related to malignancy</li> </ul><li>Normal anion gap metabolic acidosis</li><ul> <li>(1) Due to decreased proximal tubule reclamation of bicarbonate</li><li>(2) Type II renal tubular acidosis (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li> </ul><li>Chloride:phosphorus ratio > 33
<blockquote style="color: blue; ">Primary HPTH: ↑ serum calcium/PTH; ↓ serum phosphorus/bicarbonate; chloride/phosphorus ratio > 33; ↑ serum calcitriol</blockquote></li><ul> <li>Ratio < 29:1 <i>excludes</i> primary HPTH.</li> </ul><li>Increased serum 1,25-(OH)<sub>2</sub>D</li><ul> <li>PTH increases synthesis of 1α-hydroxylase in proximal renal tubule</li> </ul><li>Electrocardiogram shows shortening of QT interval.</li> </ol><li>Localization of adenoma</li><ul> <li>Technetium-99m-sestamibi radionuclide scan</li> </ul><li>Treatment</li><ol type="a"> <li>Surgical removal of the adenoma</li><li>Treatment of hypercalcemia</li><ul> <li>(1) IV hydration with normal saline followed by IV furosemide</li><ul> <li>Most common therapy</li> </ul><li>(2) Bisphosphonates</li><li>(3) Cinacalcet directly lowers PTH levels</li><ul> <li>Increases the calcium-sensing receptor to extracellular calcium</li> </ul> </ul> </ol><li>Other causes of hypercalcemia (<span>[[Table 22-4|Table 22-4. OTHER CAUSES OF HYPERCALCEMIA]]</span>)</li><ol type="a"> <li>Primary HPTH and the hypercalcemia of malignancy (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>) account for ∼80% of all cases of hypercalcemia.
<blockquote style="color: blue; ">Primary HPTH vs. malignancy: ↑ PTH in former, ↓ PTH in latter</blockquote></li><li>The primary differentiating feature between the above two diagnoses is serum PTH.</li><ul> <li>(1) Serum PTH is increased in primary HPTH.
<blockquote style="color: blue; ">Malignancy: most common cause of hypercalcemia in the hospital</blockquote></li><li>(2) Serum PTH is decreased in hypercalcemia of malignancy.</li> </ul><li>Hypercalcemia in pregnancy can produce hypocalcemia in fetus.</li><ul> <li>Suppression of PTH in the fetus</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC022034"></a> <br><a name="P022041"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Secondary HPTH: compensation for hypocalcemia</blockquote>
<ol type="1"> <li>Hyperplasia of all four parathyroid glands</li><ol type="a"> <li>Compensation for hypocalcemia</li><li>Example-hypovitaminosis D due to renal failure and malabsorption</li> </ol><li>Decreased calcium, increased PTH</li><li>May develop tertiary hyperparathyroidism</li><ol type="a"> <li>Glands become autonomous regardless of calcium level.</li><li>May bring serum calcium into a normal or increased range</li> </ol> </ol>
</div></html>
<html><a name="HC022035"></a><span>[[Fig. 22-19|Figure 22-19]]</span> <br> <br> </html>
<html><a name="HC022036"></a> <br><a name="P022042"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes of hypophosphatemia (<span>[[Table 22-5|Table 22-5. CAUSES OF HYPOPHOSPHATEMIA]]</span>)
<blockquote style="color: blue; ">Insulin therapy: danger of developing hypophosphatemia</blockquote></li><li>Clinical findings in hypophosphatemia</li><ol type="a"> <li>Muscle weakness</li><ul> <li>(1) Decreased synthesis of adenosine triphosphate (ATP) causes muscle weakness.</li><li>(2) Muscle paralysis and rhabdomyolysis may occur.
<blockquote style="color: blue; ">Hypophosphatemia: alkalosis most common cause</blockquote></li> </ul><li>RBC hemolysis</li><ul> <li>RBCs require ATP to maintain pumps and membrane integrity.</li> </ul><li>Osteomalacia (soft bones)</li><ul> <li>Phosphorus is required to mineralize bone (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>).</li> </ul> </ol><li>Causes of hyperphosphatemia (<span>[[Table 22-6|Table 22-6. CAUSES OF HYPERPHOSPHATEMIA]]</span>)
<blockquote style="color: blue; ">Hyperphosphatemia: most common cause is renal failure</blockquote></li><li>Clinical findings in hyperphosphatemia</li><ol type="a"> <li>Metastatic calcification</li><ul> <li>Excess phosphorus drives calcium into normal tissue</li> </ul><li>Hypovitaminosis D</li><ul> <li>Hyperphosphatemia inhibits the synthesis of 1α-hydroxylase.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC022037"></a><span>[[Table 22-7|Table 22-4. OTHER CAUSES OF HYPERCALCEMIA]]</span> <br> <br></html>
![[22.VI.A.Clinical anatomy and physiology]]
<<tiddler [[22.VI.A.Clinical anatomy and physiology]]>>
![[22.VI.B.Hypoparathyroidism]]
<<tiddler [[22.VI.B.Hypoparathyroidism]]>>
![[22.VI.C.Primary hyperparathyroidism (HPTH)]]
<<tiddler [[22.VI.C.Primary hyperparathyroidism (HPTH)]]>>
![[22.VI.D.Secondary hyperparathyroidism]]
<<tiddler [[22.VI.D.Secondary hyperparathyroidism]]>>
![[22.VI.E.Schematic summarizing serum PTH and calcium relationships (Fig. 22-19)]]
<<tiddler [[22.VI.E.Schematic summarizing serum PTH and calcium relationships (Fig. 22-19)]]>>
![[22.VI.F.Phosphorus disorders]]
<<tiddler [[22.VI.F.Phosphorus disorders]]>>
![[22.VI.G.Summary table integrating calcium, phosphorus, 25-(OH)D, 1,25-(OH)D, and PTH in calcium and phosphorus disorders (Table 22-7)]]
<<tiddler [[22.VI.G.Summary table integrating calcium, phosphorus, 25-(OH)D, 1,25-(OH)D, and PTH in calcium and phosphorus disorders (Table 22-7)]]>>
<html><a name="HC022039"></a><span>[[Fig. 22-20|Figure 22-20]]</span> <br> <br><a name="P022049"></a><div class="PA" style="color: black; "><ol type="1"> <li>Zona glomerulosa produces mineralocorticoids (e.g., aldosterone).</li><ul> <li>Angiotensin II activates 18-hydroxylase, which converts corticosterone to aldosterone.</li> </ul><li>Zona fasciculata produces glucocorticoids.</li><ul> <li>11-Deoxycortisol and cortisol are 17-hydroxycorticoids (17-OH).</li> </ul><li>Zona reticularis produces sex hormones.</li><ol type="a"> <li>17-Ketosteroids (17-KS)</li><ul> <li>Dehydroepiandrosterone (DHEA) and androstenedione
<blockquote style="color: blue; ">Peripheral tissue sites: skin, testis, prostate, seminal vesicles, epididymis, liver</blockquote></li> </ul><li>Testosterone</li><ul> <li>Converted to dihydrotestosterone (DHT) by 5α-reductase in peripheral tissue sites</li> </ul> </ol> </ol>
</div></html>
![[22.VII.A.Adrenal cortex hormones (Fig. 22-20)]]
<<tiddler [[22.VII.A.Adrenal cortex hormones (Fig. 22-20)]]>>
![[22.VII.B.Adrenal medulla]]
<<tiddler [[22.VII.B.Adrenal medulla]]>>
![[22.VII.C.Adrenocortical hypofunction (primary hypocortisolism)]]
<<tiddler [[22.VII.C.Adrenocortical hypofunction (primary hypocortisolism)]]>>
![[22.VII.D.Adrenocortical hyperfunction]]
<<tiddler [[22.VII.D.Adrenocortical hyperfunction]]>>
![[22.VII.E.Adrenal medulla hyperfunction]]
<<tiddler [[22.VII.E.Adrenal medulla hyperfunction]]>>
<html><a name="HC022040"></a> <br><a name="P022050"></a><div class="PA" style="color: black; "><ol type="1"> <li>Neural crest origin</li><li>Produces catecholamines
<blockquote style="color: blue; ">Adrenal medulla: produce catecholamines</blockquote></li><ul> <li>Epinephrine (EPI) and norepinephrine (NOR)</li> </ul><li>Metabolic products of EPI and NOR
<blockquote style="color: blue; ">Metabolic end-products of EPI/NOR: metanephrines, VMA</blockquote></li><ul> <li>Metanephrine and vanillylmandelic acid (VMA)</li> </ul><li>Metabolic product of dopamine is homovanillic acid (HVA).</li> </ol>
</div></html>
<html><a name="HC022041"></a> <br><a name="PB022004"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Aldosterone</b> enhances the exchange of sodium for potassium in the kidneys. Hence, its deficiency leads to a hypertonic loss of sodium in the urine (hyponatremia) and retention of potassium (hyperkalemia). Aldosterone also enhances the proton pump. Deficiency leads to retention of protons and metabolic acidosis (normal anion gap type).</div><a name="P022051"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acute adrenocortical insufficiency</li><ol type="a"> <li>Causes</li><ul> <li>(1) Abrupt withdrawal of corticosteroids
<blockquote style="color: blue; ">Abrupt withdrawal of corticosteroids: most common cause of acute adrenocortical insufficiency</blockquote></li><li>(2) Waterhouse-Friderichsen syndrome (see later discussion)</li><li>(3) Anticoagulation therapy</li> </ul><li>Waterhouse-Friderichsen syndrome</li><ul> <li>(1) Usually associated with septicemia from <i>Neisseria meningitidis</i></li><li>(2) Patients develop endotoxic shock.
<blockquote style="color: blue; ">Waterhouse-Friderichsen syndrome: <i>N. meningitidis</i> sepsis → DIC → bilateral adrenal hemorrhage</blockquote></li><ul> <li>Release of tissue thromboplastin causes disseminated intravascular coagulation (DIC).</li> </ul><li>(3) Bilateral adrenal hemorrhage</li><ul> <li>Fibrin clots in vessels cause hemorrhagic infarction.</li> </ul> </ul> </ol><li>Chronic adrenal insufficiency (Addison's disease)
<blockquote style="color: blue; ">Autoimmune disease: most common cause of Addison's disease in U.S.</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Causes</li><ul> <li>(a) Autoimmune destruction</li><ul> <li>Most common cause (80% of cases)</li> </ul><li>(b) Miliary tuberculosis (15% of cases/histoplasmosis)
<blockquote style="color: blue; ">Miliary TB: most common cause of Addison's disease in developing countries</blockquote></li><li>(c) Adrenogenital syndrome (see later discussion)</li><li>(d) Metastasis</li><ul> <li>Most often from a primary lung cancer
<blockquote style="color: blue; ">Most common cause of Addison's disease in children: adrenogenital syndrome</blockquote></li> </ul><li>(e) AIDS (30% of patients)</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Weakness and hypotension</li><ul> <li>Due to sodium loss from mineralocorticoid and glucocorticoid deficiency</li> </ul><li>(2) Diffuse hyperpigmentation (<span>[[Fig. 22-21|Figure 22-21]]</span>)
<blockquote style="color: blue; ">Addison's disease: diffuse hyperpigmentation; hypotension, weakness</blockquote></li><ul> <li>(a) Increased plasma ACTH stimulates melanocytes.</li><li>(b) Buccal mucosa, skin, skin creases</li> </ul> </ul><li>Laboratory findings</li><ul> <li>(1) Short and prolonged ACTH stimulation test
<blockquote style="color: blue; ">Metyrapone test: ↓ cortisol → ↑ ACTH → ↓ 11-deoxycortisol</blockquote></li><ul> <li><i>No</i> increase in cortisol or 17-OH</li> </ul><li>(2) Metyrapone test (<span>[[Fig. 22-22|Figure 22-22]]</span>)</li><ul> <li>Increased ACTH but <i>no</i> increase in 11-deoxycortisol</li> </ul><li>(3) Increased plasma ACTH
<blockquote style="color: blue; ">Addison's disease: ↓ serum sodium, cortisol, bicarbonate; ↑ serum potassium, ACTH</blockquote></li><li>(4) Electrolyte findings (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li><ul> <li>Hyponatremia, hyperkalemia, and metabolic acidosis</li> </ul><li>(5) Fasting hypoglycemia
<blockquote style="color: blue; ">Addison's disease: hypoglycemia, eosinophilia, lymphocytosis, neutropenia</blockquote></li><ul> <li>Due to decrease in cortisol (cortisol is gluconeogenic)</li> </ul><li>(6) Eosinophilia, lymphocytosis, and neutropenia</li><ul> <li>Due to decrease in cortisol (refer to <span macro="tag [[12 White Blood Cell Disorders]] [[Chapter 12]]"></span>)</li> </ul> </ul><li>Treatment</li><ul> <li>Glucocorticoid and mineralocorticoid replacement</li> </ul> </ol><li>Adrenogenital syndrome (congenital adrenal hyperplasia)
<blockquote style="color: blue; ">↑ 17-KS, testosterone, DHT: ambiguous genitalia females; precocious puberty males and females</blockquote></li><ol type="a"> <li>Autosomal recessive disorders</li><ul> <li>Use <span>[[Figure 22-20|Figure 22-20]]</span> to understand changes in steroid synthesis</li> </ul><li>Enzyme deficiency causes hypocortisolism and corresponding increase in ACTH.</li><ul> <li>(1) Increase in ACTH</li><ul> <li>Causes adrenocortical hyperplasia and diffuse skin pigmentation</li> </ul><li>(2) Increase in 17-KS, testosterone, and DHT; causes:
<blockquote style="color: blue; ">Newborn with ambiguous genitalia: first step is to determine genetic sex with chromosome analysis</blockquote></li><ul> <li>(a) Ambiguous genitalia in females (<span>[[Fig. 22-23|Figure 22-23]]</span>)</li><ul> <li>Primarily due to DHT; first step is to check the genetic sex of the newborn with a chromosome analysis</li> </ul><li>(b) Precocious puberty may develop in males and females.</li><ul> <li>In girls, excess androgens are aromatized in peripheral tissue to estrogen.</li> </ul><li>(c) Girls experience irregular menses and infertility as adults.</li><li>(d) Both sexes have rapid growth in childhood, but early fusion of epiphyses.</li><ul> <li>Majority have short stature as adults.
<blockquote style="color: blue; ">↓ 17-KS, testosterone, DHT: delayed menarche and secondary sex characteristics; males develop pseudohermaphroditism</blockquote></li> </ul> </ul><li>(3) Decrease in 17-KS, testosterone, and DHT causes hypogonadism in both sexes.</li><ul> <li>(a) Females have delay in menarche and development of secondary sex characteristics; recall that female hormones come from androgens.</li><li>(b) Males develop pseudohermaphroditism.</li><ul> <li>Male external genitalia development requires DHT (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>).
<blockquote style="color: blue; ">↑ Mineralocorticoids: sodium retention with hypertension</blockquote></li> </ul> </ul><li>(4) Increase in mineralocorticoids</li><ul> <li>Causes sodium retention leading to hypertension</li> </ul><li>(5) Decrease in mineralocorticoids; causes:</li><ul> <li>(a) Sodium loss (hyponatremia), hyperkalemia
<blockquote style="color: blue; ">↓ Mineralocorticoids: sodium losers with hypotension</blockquote></li><li>(b) Hypotension and possible hypovolemic shock</li> </ul> </ul><li>Substrates proximal to the enzyme block increase
<blockquote style="color: blue; ">Classic 21-OHase deficiency: most common cause of adrenogenital syndrome</blockquote></li><li>Substrates distal to the enzyme block decrease</li><li>Classic 21-hydroxylase (OHase) deficiency</li><ul> <li>(1) Most common enzyme deficiency (90-95% of cases)</li><li>(2) Increase in 17-KS, testosterone, and DHT
<blockquote style="color: blue; ">Classic 21-OHase deficiency: impaired cortisol and mineralocorticoid production (salt loser); ↑ androgens</blockquote></li><li>(3) Decrease in mineralocorticoids (salt losers)</li><li>(4) Decrease in 17-OH</li><li>(5) Increase in 17-hydroxyprogesterone</li> </ul><li>Nonclassic 21-hydroxylase deficiency</li><ul> <li>(1) Impaired cortisol production but normal mineralocorticoid production (not sodium wasting)
<blockquote style="color: blue; ">Nonclassic 21-OHase deficiency: impaired cortisol synthesis only; virilization</blockquote></li><li>(2) Ambiguous genitalia in females and virilization; precocious puberty in boys</li> </ul><li>11-Hydroxylase deficiency</li><ul> <li>(1) Increase in 17-KS, testosterone, and DHT</li><li>(2) Increase in mineralocorticoids (11-deoxycorticosterone); salt retainers
<blockquote style="color: blue; ">11-OHase deficiency: impaired cortisol + mineralocorticoid excess (salt retainer); ↑ androgens</blockquote></li><li>(3) Increase in 17-OH (11-deoxycortisol is proximal to the block)</li><li>(4) Increase in 17-hydroxyprogesterone</li> </ul><li>17-Hydroxylase deficiency</li><ul> <li>(1) Decrease in 17-KS, 17-OH, 17-hydroxyprogesterone, testosterone, and DHT</li><li>(2) Increase in mineralocorticoids (salt retainers)</li> </ul><li>Diagnosis of adrenogenital syndrome
<blockquote style="color: blue; ">17-OHase deficiency: impaired cortisol and androgens; ↑ mineralocorticoid production</blockquote></li><ul> <li>(1) Serum 17-OH progesterone is an excellent screening test</li><ul> <li>(a) Increased in 21- and 11-OHase deficiency</li><li>(b) Decreased in 17-OHase deficiency</li><li>(c) Can measure prenatally with chorionic villous sampling
<blockquote style="color: blue; ">17-OH progesterone: excellent screening test; ↑ 21- and 11-OHase deficiency; ↓ 17-OHase deficiency</blockquote></li><li>(d) Screening test in most but not all states on newborns</li> </ul><li>(2) Urine for 17-hydroxycorticoids and 17-ketosteroids</li> </ul><li>Treatment</li><ul> <li>(1) Glucocorticoids</li><li>(2) Mineralocorticoids (21-OHase deficiency)</li><li>(3) Estrogen or testosterone at time of puberty</li> </ul><li>Summary of adrenogenital syndrome (<span>[[Table 22-8|Table 22-8. SUMMARY OF ADRENOGENITAL SYNDROMES]]</span>)</li> </ol> </ol>
</div></html>
<html><a name="HC022042"></a> <br><a name="PB022005"></a><div class="BB" style="color: rgb(47, 79, 79); ">In <b>primary hyperaldosteronism</b>, there is increased exchange of sodium (hypernatremia) for potassium (hypokalemia). Sodium exchanges with hydrogen ions when potassium is depleted, causing a loss of hydrogen ions in the urine and a corresponding increase in bicarbonate reabsorption (metabolic alkalosis). Hypernatremia increases plasma volume, which increases renal blood flow and inhibits plasma renin activity. Chronic retention of sodium produces hypertension. Hypokalemia produces muscle weakness.
<blockquote style="color: blue; ">Primary hyperaldosteronism: hypertension, hypernatremia, hypokalemia, metabolic alkalosis</blockquote></div><a name="P022052"></a><div class="PA" style="color: black; "><ol type="1"> <li>Cushing syndrome</li><ol type="a"> <li>Causes</li><ul> <li>(1) Prolonged corticosteroid therapy
<blockquote style="color: blue; ">Cushing syndrome: most common cause is corticosteroid therapy (iatrogenic)</blockquote></li><ul> <li>Most common cause</li> </ul><li>(2) Pituitary Cushing syndrome (Cushing disease)</li><ul> <li>(a) 60% of cases</li><li>(b) Due to a pituitary adenoma
<blockquote style="color: blue; ">Cushing syndrome: pituitary Cushing most common pathologic cause</blockquote></li><li>(c) Increased ACTH and cortisol</li> </ul><li>(3) Adrenal Cushing syndrome
<blockquote style="color: blue; ">Pituitary Cushing: ↑ ACTH, ↑ cortisol</blockquote></li><ul> <li>(a) 25% of cases</li><li>(b) Most often due to an adenoma</li><li>(c) Markedly decreased ACTH and increased cortisol
<blockquote style="color: blue; ">Adrenal Cushing: ↓ ACTH, ↑ cortisol</blockquote></li> </ul><li>(4) Ectopic Cushing syndrome
<blockquote style="color: blue; ">Ectopic Cushing: ↑↑ ACTH, ↑ cortisol</blockquote></li><ul> <li>(a) 15% of cases</li><li>(b) Usually small cell carcinoma of lung; less commonly thymus, thyroid</li><ul> <li>Ectopic ACTH production</li> </ul><li>(c) Markedly increased ACTH and cortisol</li> </ul> </ul><li>Clinical findings
<blockquote style="color: blue; ">Cushing syndrome: truncal obesity, thin extremities, purple stria</blockquote></li><ul> <li>(1) Weight gain</li><ul> <li>(a) Due to hyperinsulinism from hyperglycemia</li><ul> <li>Insulin increases storage of fat (triglyceride) in adipose; also has mineralocorticoid effects and retains sodium</li> </ul><li>(b) Fat deposition in face ("moon facies"), upper back ("buffalo hump"), and trunk (truncal obesity) (<span>[[Fig. 22-24|Figure 22-24]]</span>)</li> </ul><li>(2) Muscle weakness</li><ul> <li>(a) Cortisol breaks down muscles in the extremities (thin extremities).</li><li>(b) Muscles supply amino acids (e.g., alanine) for gluconeogenesis.</li> </ul><li>(3) Diastolic hypertension
<blockquote style="color: blue; ">Hypercortisolism: thin extremities, purple stria</blockquote></li><ul> <li>(a) Due to increase in weak mineralocorticoids and glucocorticoids</li><li>(b) Aldosterone is <i>not</i> increased (requires angiotensin II)
<blockquote style="color: blue; ">Hyperinsulinemia: truncal obesity</blockquote></li> </ul><li>(4) Hirsutism</li><ul> <li>Due to increased androgens</li> </ul><li>(5) Purple abdominal stria</li><ul> <li>Cortisol weakens collagen, causing rupture of blood vessels in stretch marks.
<blockquote style="color: blue; ">Cushing: hypertension; hirsutism</blockquote></li> </ul><li>(6) Osteoporosis</li><ul> <li>Hypercortisolism causes increased breakdown of bone.
<blockquote style="color: blue; ">Screening tests: ↑ urine free cortisol; no suppression of cortisol with low dose of dexamethasone</blockquote></li> </ul> </ul><li>Laboratory findings</li><ul> <li>(1) Increased urine for free cortisol</li><ul> <li>Very high positive and negative predictive value</li> </ul><li>(2) Low-dose dexamethasone (cortisol analogue) suppression test</li><ul> <li><i>Cannot</i> suppress cortisol in all types
<blockquote style="color: blue; ">Pituitary Cushing syndrome: suppression of cortisol by high-dose dexamethasone</blockquote></li> </ul><li>(3) High-dose dexamethasone suppression test</li><ul> <li>Can suppress cortisol in pituitary Cushing syndrome but <i>not</i> the other types</li> </ul><li>(4) Hyperglycemia</li><ul> <li>(a) Cortisol enhances gluconeogenesis.
<blockquote style="color: blue; ">Cushing: hyperglycemia; hypokalemia; metabolic alkalosis</blockquote></li><li>(b) Stimulates the release of insulin</li> </ul><li>(5) Hypokalemic metabolic alkalosis</li><ul> <li>Due to increased weak mineralocorticoids</li> </ul> </ul><li>Nelson's syndrome</li><ul> <li>(1) Bilateral adrenalectomy causes enlargement of a preexisting pituitary adenoma.</li><ul> <li>Sudden drop in cortisol causes an increase in synthesis of ACTH.</li> </ul><li>(2) Clinical findings of headache and diffuse hyperpigmentation
<blockquote style="color: blue; ">Nelson's syndrome: bilateral adrenalectomy causes enlargement of preexisting pituitary adenoma</blockquote></li> </ul><li>Summary of Cushing syndrome (<span>[[Table 22-9|Table 22-9. SUMMARY OF PITUITARY, ADRENAL, AND ECTOPIC CUSHING SYNDROME (CS)]]</span>)</li> </ol><li>Hyperaldosteronism</li><ol type="a"> <li>Primary aldosteronism (Conn's syndrome; refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span> for full discussion)</li><ul> <li>(1) Most often due to a benign adenoma in the zona glomerulosa</li><li>(2) Clinical findings</li><ul> <li>(a) Diastolic hypertension</li><li>(b) Muscle weakness, tetany (from metabolic alkalosis)</li> </ul><li>(3) Laboratory findings (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>; see <span>[[Fig. 4-8|Figure 4-8]]</span>)</li><ul> <li>(a) Hypernatremia, hypokalemia, metabolic alkalosis</li><li>(b) Decreased plasma renin activity</li> </ul> </ul><li>Secondary aldosteronism
<blockquote style="color: blue; ">Secondary aldosteronism: compensation for ↓cardiac output; activation of RAA system</blockquote></li><ul> <li>(1) Compensatory reaction related to a decrease in cardiac output</li><li>(2) Decreased renal blood flow activates the renin-angiotensin-aldosterone (RAA) system.</li><li>(3) Plasma renin activity is increased.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC022043"></a> <br><a name="P022053"></a><div class="PA" style="color: black; "><ul> <li>Increased production of catecholamines causes hypertension.</li><ol type="1"> <li>Pheochromocytoma</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Unilateral (∼90% of cases)</li><li>(2) Benign adenoma (∼90% of cases)</li><li>(3) Arises in the adrenal medulla (∼90% of cases)</li><ul> <li>Other sites-bladder, organ of Zuckerkandl near the bifurcation of the aorta, posterior mediastinum
<blockquote style="color: blue; ">Pheochromocytoma: majority benign, unilateral, arise in adrenal medulla</blockquote></li> </ul><li>(4) <i>N</i>-methyltransferase converts NOR to EPI (<span>[[Fig. 22-25|Figure 22-25]]</span>).</li><ul> <li>(a) Adrenal medulla and the organ of Zuckerkandl contain the enzyme.</li><ul> <li>Pheochromocytoma produces NOR and EPI.</li> </ul><li>(b) Other sites lack the enzyme.</li><ul> <li>Pheochromocytoma produces only NOR.</li> </ul> </ul><li>(5) Associations
<blockquote style="color: blue; ">Associations: neurofibromatosis; MEN IIa/IIb; von Hippel-Lindau disease</blockquote></li><ul> <li>(a) Neurofibromatosis (5% in type 1; refer to <span macro="tag [[25 Nervous System and Special Sensory Disorders]] [[Chapter 25]]"></span>)</li><li>(b) MEN IIa and IIb (MEN III)</li><ul> <li>Mutation in RET protooncogene</li> </ul><li>(c) Von Hippel-Lindau disease (often bilateral tumors)</li><ul> <li>Mutation in VHL gene</li> </ul> </ul> </ul><li>Tumor characteristics</li><ul> <li>Brown, hemorrhagic, and often necrotic</li> </ul><li>Clinical findings
<blockquote style="color: blue; ">Unique findings: palpitations, paroxysmal hypertension, anxiety, drenching sweats, headache</blockquote></li><ul> <li>(1) Diastolic hypertension</li><ul> <li>(a) Sustained (55%)</li><li>(b) Paroxysmal bursts (45%)</li><ul> <li><i>N</i>ot present in essential hypertension</li> </ul> </ul><li>(2) Pounding headache (80%)</li><li>(3) Palpitations (70%)</li><ul> <li>(a) With or without tachycardia</li><li>(b) Palpitations are <i>not</i> present in essential hypertension.</li> </ul><li>(4) Drenching sweats (hyperhidrosis; 70%)</li><ul> <li>(a) Correlates with paroxysms of hypertension</li><li>(b) Hyperhidrosis is <i>not</i> present in essential hypertension.</li> </ul><li>(5) Anxiety</li><ul> <li>(a) Correlates with paroxysms of hypertension</li><li>(b) Anxiety is <i>not</i> present in essential hypertension.</li> </ul><li>(6) Chest pain from subendocardial ischemia
<blockquote style="color: blue; ">Pheochromocytoma: orthostatic hypotension, chest pain, ileus</blockquote></li><li>(7) Orthostatic hypotension</li><ul> <li>Plasma volume is reduced owing to vasoconstriction of arterioles/venules</li> </ul><li>(8) Ileus</li><ul> <li>Catecholamines inhibit peristalsis.</li> </ul> </ul><li>Laboratory findings</li><ul> <li>(1) Increased plasma free metanephrines
<blockquote style="color: blue; ">Diagnosis: plasma free metanephrines best screen</blockquote></li><ul> <li>Best test to screen and confirm pheochromocytoma</li> </ul><li>(2) Increased plasma normetanephrine</li><li>(3) Increased 24-hour urine for metanephrine (100% sensitivity)
<blockquote style="color: blue; ">Urine tests: 24-hour collection for metanephrine (best test), VMA</blockquote></li><li>(4) Increased 24-hour urine for VMA</li><li>(5) Lack of suppression of plasma norepinephrine with clonidine</li><li>(6) Hyperglycemia</li><ul> <li>Increased glycogenolysis and gluconeogenesis
<blockquote style="color: blue; ">Pheochromocytoma: hyperglycemia, neutrophilic leukocytosis</blockquote></li> </ul><li>(7) Neutrophilic leukocytosis</li><ul> <li>Inhibition of neutrophil adhesion molecules (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>)</li> </ul> </ul><li>Treatment is surgery.</li><ul> <li>(1) Preoperative stabilization</li><ul> <li>(a) Phenoxybenzamine</li><li>(b) β-Blocker</li><li>(c) Metyrosine (catecholamine synthesis inhibitor)</li><li>(d) Liberal fluid and salt intake</li> </ul><li>(2) Preoperative or intraoperative hypertensive crisis</li><ul> <li>Phentolamine or nitroprusside in concert with a β-adrenergic blocker</li> </ul> </ul> </ol><li>Neuroblastoma
<blockquote style="color: blue; ">Neuroblastoma: malignant tumor postganglionic sympathetic neurons</blockquote></li><ol type="a"> <li>Malignant tumor</li><ul> <li>(1) Neoplasm of postganglionic sympathetic neurons</li><li>(2) Most often occurs in children < 5 years old</li><ul> <li>(a) Third most common cancer</li><li>(b) Mean age of onset 18 months
<blockquote style="color: blue; ">Neuroblastoma: childhood tumor and cause of hypertension</blockquote></li> </ul><li>(3) Primarily located in the adrenal medulla</li><ul> <li>Occasionally located in the posterior mediastinum (paraspinal)</li> </ul><li>(4) Amplification of <i>N-MYC</i> oncogene (nuclear transcriber)</li><li>(5) Opsoclonus-myoclonus syndrome
<blockquote style="color: blue; ">Opsoclonus-myoclonus syndrome: paraneoplastic syndrome; myoclonic jerk; chaotic eye movements</blockquote></li><ul> <li>(a) Paraneoplastic syndrome</li><li>(b) Myoclonic jerks of extremities</li><li>(c) Chaotic eye movements in all directions</li><li>(d) Associated with neuroblastoma in 20% to 50% of cases</li> </ul> </ul><li>Commonly metastasize to skin and bones</li><ul> <li>Approximately 70% have metastases at the time of diagnosis.</li> </ul><li>Prognosis depends on age.</li><ul> <li>Children < 1 year old have a good prognosis.</li> </ul><li>"Small cell" tumor</li><ul> <li>(1) Composed of malignant neuroblasts
<blockquote style="color: blue; ">Neuroblastoma: "small cell" tumor; neurosecretory granules</blockquote></li><li>(2) Presence of Homer-Wright rosettes</li><ul> <li>Neuroblasts are located around a central space.</li> </ul><li>(3) Electron microscopy shows neurosecretory granules.</li> </ul><li>Clinical and laboratory findings
<blockquote style="color: blue; ">Neuroblastoma: child with abdominal mass + hypertension</blockquote></li><ul> <li>(1) Palpable abdominal mass</li><li>(2) Diastolic hypertension</li><li>(3) Increased urine VMA and HVA (90-95% sensitivity)</li> </ul><li>Diagnosis</li><ul> <li>(1) Urine collections for VMA and HVA</li><li>(2) Imaging studies</li><ul> <li>(a) Body scan with <sup>131</sup>I-MIBG (metaiodobenzylguanidine)</li><ul> <li>Malignant cells pick up the radioactive material.</li> </ul><li>(b) Bone scans to detect lytic lesions</li> </ul> </ul><li>Treatment</li><ul> <li>(1) Depends on age, stage of disease</li><li>(2) Surgery; irradiation; multiagent chemotherapy
<blockquote style="color: blue; ">Insulinoma: ↑ serum insulin; ↑ C-peptide</blockquote></li> </ul><li>Prognosis</li><ul> <li>(1) Overall survival is 40%.
<blockquote style="color: blue; ">Patient injecting excess insulin: ↑ serum insulin; ↓C-peptide</blockquote></li><li>(2) Children < 1 year old have 90% cure rate.</li> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC022044"></a><span>[[Table 22-10|Table 22-10. SUMMARY OF ISLET CELL TUMORS]]</span> <br> <br></html>
![[22.VIII.A.Islet Cell Tumors (Table 22-10)]]
<<tiddler [[22.VIII.A.Islet Cell Tumors (Table 22-10)]]>>
<html><a name="HC022054"></a> <br><a name="P022070"></a><div class="PA" style="color: black; "><ol type="1"> <li>Autosomal recessive</li><li>Mean age of onset is 12 years old.</li><li>No HLA relationship</li><li>Clinical findings
<blockquote style="color: blue; ">Type I: Addison's disease, primary hypoparathyroidism, mucocutaneous candidiasis</blockquote></li><ol type="a"> <li>Addison's disease</li><li>Primary hypoparathyroidism</li><li>Mucocutaneous candidiasis</li> </ol> </ol>
</div></html>
<html><a name="HC022055"></a> <br><a name="P022071"></a><div class="PA" style="color: black; "><ol type="1"> <li>Autosomal dominant</li><li>Mean age of onset is 24 years old.</li><li>HLA-DR3 and -DR4</li><li>Clinical findings
<blockquote style="color: blue; ">Type II: Addison's disease, Hashimoto's thyroiditis, type 1 diabetes mellitus</blockquote></li><ol type="a"> <li>Addison's disease</li><li>Hashimoto's thyroiditis</li><li>Type 1 diabetes mellitus</li> </ol> </ol>
</div></html>
![[22.X.A.Type I polyglandular syndrome]]
<<tiddler [[22.X.A.Type I polyglandular syndrome]]>>
![[22.X.B.Type II polyglandular syndrome]]
<<tiddler [[22.X.B.Type II polyglandular syndrome]]>>
<html><a name="HC022057"></a> <br><a name="P022072"></a><div class="PA" style="color: black; "><ol type="1"> <li>Difficult to arrive at a consensus for a cut-off point</li><li>Ranges have been anywhere from 40 to 70 mg/dL (normal fasting 70-110 mg/dL)</li><li>Reasonable cut-off point is <50 mg/dL.</li> </ol>
</div></html>
<html><a name="HC022058"></a> <br><a name="PB022009"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Idiopathic postprandial syndrome (IPS):</b> This syndrome is characterized by the presence of adrenergic symptoms <i>without</i> demonstrable evidence of hypoglycemia. Patients also complain of lack of energy, mental dullness, and inability to concentrate. Symptoms usually disappear if mixed carbohydrate-protein meals are eaten at frequent intervals.</div><a name="P022073"></a><div class="PA" style="color: black; "><ol type="1"> <li>Reactive type of hypoglycemia
<blockquote style="color: blue; ">Hypoglycemia: subdivided into fed state and fasting state</blockquote></li><li>Causes</li><ol type="a"> <li>Insulin treatment in type 1 diabetes</li><ul> <li>(1) Most common cause</li><li>(2) Sulfonylurea-related hypoglycemia is less common.
<blockquote style="color: blue; ">Reactive hypoglycemia: excess insulin most common cause; adrenergic symptoms</blockquote></li> </ul><li>IGT or type 2 diabetes</li><ul> <li>Excessive amount of insulin is released for the glucose absorbed.</li> </ul> </ol><li>Develop adrenergic symptoms ∼1 to 5 hours after eating:</li><ol type="a"> <li>Sweating, trembling, anxiety</li><li>Palpitations, tachycardia, mydriasis</li><li>Numbness and tingling</li> </ol><li>Treatment</li><ol type="a"> <li>Carbohydrate intake (grape juice, candy)</li><li>Glucagon IM injection</li> </ol> </ol>
</div></html>
<html><a name="HC022059"></a> <br><a name="PB022010"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Carnitine</b> is required for the synthesis of carnitine acyltransferase (CAT). CAT is the rate-limiting reaction of β-oxidation of fatty acids, which are an important source of energy in the fasting and starvation states for muscle tissue. Any excess of acetyl CoA, the end-product of β-oxidation, is used by the liver to synthesize ketone bodies. Ketone bodies are used for energy by muscle in the fasting state and by the brain in starvation. Therefore, in carnitine deficiency, a decrease in CAT significantly reduces the amount of fatty acids and ketone bodies as sources of energy. This leaves glucose as the only fuel available for all tissues to use for energy, which results in hypoglycemia.</div><a name="P022074"></a><div class="PA" style="color: black; "><ol type="1"> <li>Fasting state hypoglycemia
<blockquote style="color: blue; ">Fasting hypoglycemia: alcohol excess; insulinoma; cirrhosis</blockquote></li><li>Causes</li><ol type="a"> <li>Alcohol (see <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>)</li><ul> <li>(1) Increased nicotinamide adenine dinucleotide (NADH) converts pyruvate to lactate.</li><ul> <li>Less pyruvate for gluconeogenesis
<blockquote style="color: blue; ">Alcohol excess: ↓ glycogen stores; ↓ gluconeogenesis (pyruvate converted to lactate)</blockquote></li> </ul><li>(2) Decreased glycogen stores in severe liver disease</li> </ul><li>Renal failure</li><ul> <li>Kidney is a site of gluconeogenesis.</li> </ul><li>Malnutrition</li><li>Chronic liver disease</li><ul> <li>Decreased gluconeogenesis, glycogen depletion</li> </ul><li>Insulinoma, hypopituitarism (decreased GH and cortisol)</li><li>Ketotic hypoglycemia in childhood
<blockquote style="color: blue; ">Fasting hypoglycemia children: look for inborn errors of metabolism</blockquote></li><ul> <li>(1) Most common cause of hypoglycemia from 18 months to mid-childhood</li><li>(2) Multiple etiologies</li><ul> <li>(a) Maple syrup urine disease, galactosemia, hereditary fructose intolerance, von Gierke's glycogen storage disease (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><li>(b) Carnitine deficiency</li> </ul> </ul> </ol><li>Neuroglycopenic symptoms
<blockquote style="color: blue; ">Neuroglycopenia: dizziness, mental status changes, motor disturbances</blockquote></li><ol type="a"> <li>Dizziness, confusion, headache, inability to concentrate</li><li>Motor disturbances, seizures, visual disturbances, coma</li> </ol><li>Diagnosis
<blockquote style="color: blue; ">Diagnosis: prolonged fast; satisfy Whipple's triad</blockquote></li><ol type="a"> <li>Prolonged fast</li><li>Must satisfy Whipple's triad:</li><ul> <li>(1) Symptoms occur.</li><li>(2) Hypoglycemia is demonstrated.</li><li>(3) Symptoms are relieved by glucose.</li> </ul> </ol> </ol>
</div></html>
![[22.XI.A.Definition]]
<<tiddler [[22.XI.A.Definition]]>>
![[22.XI.B.Fed state hypoglycemia]]
<<tiddler [[22.XI.B.Fed state hypoglycemia]]>>
![[22.XI.C.Fasting type of hypoglycemia]]
<<tiddler [[22.XI.C.Fasting type of hypoglycemia]]>>
<html><a name="HC023002"></a> <br><a name="P023001"></a><div class="PA" style="color: black; "><ol type="1"> <li>Autosomal dominant (AD)</li><li>Defective synthesis of type I collagen
<blockquote style="color: blue; ">Osteogenesis imperfecta: AD; defect in synthesis type 1 collagen</blockquote></li><li>Clinical findings</li><ol type="a"> <li>Pathologic fractures at birth</li><li>Blue sclera (<span>[[Fig. 23-1|Figure 23-1]]</span>)
<blockquote style="color: blue; ">Blue sclera: reflection of underlying choroidal veins</blockquote></li><li>Deafness in some patients</li> </ol><li>Treatment</li><ul> <li>Bisphosphonates to increase bone mineralization</li> </ul> </ol>
</div></html>
<html><a name="HC023003"></a> <br><a name="P023002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Autosomal dominant</li><li>Pathogenesis</li><ol type="a"> <li>Mutation in fibroblast growth factor receptor gene
<blockquote style="color: blue; ">Achondroplasia: AD; mutation in fibroblast growth factor receptor gene</blockquote></li><ul> <li>Gene mutations increase with paternal age</li> </ul><li>Impaired proliferation of cartilage at the growth plate</li> </ol><li>Clinical findings</li><ol type="a"> <li>Normal-sized head and vertebral column
<blockquote style="color: blue; ">Achondroplasia: normal head/axial skeleton; short arms/legs</blockquote></li><li>Shortened arms and legs</li><li>Normal growth hormone and insulin growth factor-1 levels</li> </ol><li>No treatment</li> </ol>
</div></html>
![[23.I.A.Osteogenesis imperfecta ("brittle bone" disease)]]
<<tiddler [[23.I.A.Osteogenesis imperfecta ("brittle bone" disease)]]>>
![[23.I.B.Achondroplasia]]
<<tiddler [[23.I.B.Achondroplasia]]>>
![[23.I.C.Osteopetrosis ("marble bone" disease)]]
<<tiddler [[23.I.C.Osteopetrosis ("marble bone" disease)]]>>
![[23.I.D.Osteomyelitis]]
<<tiddler [[23.I.D.Osteomyelitis]]>>
![[23.I.E.Osteoporosis]]
<<tiddler [[23.I.E.Osteoporosis]]>>
![[23.I.F.Aseptic (avascular) necrosis of bone]]
<<tiddler [[23.I.F.Aseptic (avascular) necrosis of bone]]>>
![[23.I.G.Osteochondritis dissecans]]
<<tiddler [[23.I.G.Osteochondritis dissecans]]>>
![[23.I.H.Osgood-Schlatter disease]]
<<tiddler [[23.I.H.Osgood-Schlatter disease]]>>
![[23.I.I.Paget's disease of bone (osteitis deformans)]]
<<tiddler [[23.I.I.Paget's disease of bone (osteitis deformans)]]>>
![[23.I.J.Fibrous dysplasia]]
<<tiddler [[23.I.J.Fibrous dysplasia]]>>
![[23.I.K.Neoplastic disorders of bone]]
<<tiddler [[23.I.K.Neoplastic disorders of bone]]>>
<html><a name="HC023004"></a> <br><a name="P023003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Autosomal recessive (severe)</li><ul> <li>Autosomal dominant (less severe)</li> </ul><li>Pathogenesis</li><ol type="a"> <li>Deficiency osteoclasts</li><li>Normal balance of osteoblasts making bone and osteoclasts breaking down bone is disrupted favoring increased bone formation.
<blockquote style="color: blue; ">Osteopetrosis: deficiency of osteoclasts; "too much bone"</blockquote></li><li>Overgrowth and sclerosis of cortical bone ("too much bone")</li> </ol><li>Clinical findings
<blockquote style="color: blue; ">Osteopetrosis: pathologic fractures; visual/hearing loss</blockquote></li><ol type="a"> <li>Pathologic fractures</li><li>Anemia</li><ul> <li>Replacement of marrow cavity</li> </ul><li>Cranial nerve compression</li><ul> <li>Visual and hearing loss</li> </ul> </ol><li>No treatment</li> </ol>
</div></html>
<html><a name="HC023005"></a> <br><a name="P023004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Osteomyelitis in children and adults
<blockquote style="color: blue; ">Osteomyelitis: usually hematogenous spread to bone; metaphysis most common site</blockquote></li><ol type="a"> <li>Most commonly due to sepsis with subsequent spread to bone</li><li>Metaphysis is the most common site.</li><ul> <li>Favors the tibia and fibula in children</li> </ul><li>Most often due to <i>Staphylococcus aureus</i> (90% of cases)
<blockquote style="color: blue; "><i>Staphylococcus aureus:</i> most common pathogen causing osteomyelitis</blockquote></li><ul> <li>Other pathogens: <i>Streptococcus pyogenes</i>, <i>Haemophilus influenzae</i></li> </ul> </ol><li>Osteomyelitis in sickle cell disease (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)
<blockquote style="color: blue; "><i>Salmonella paratyphi</i>: osteomyelitis in sickle cell disease</blockquote></li><ul> <li>Most often due to <i>Salmonella paratyphi</i></li> </ul><li>Tuberculous osteomyelitis
<blockquote style="color: blue; ">Tuberculous osteomyelitis: commonly involves vertebral column (Pott's disease)</blockquote></li><ol type="a"> <li>Hematogenous spread from a primary lung focus</li><li>Targets vertebral column (Pott's disease)</li> </ol><li><i>Pseudomonas aeruginosa</i> osteomyelitis</li><ul> <li>Most often due to puncture of foot through rubber footwear</li> </ul><li>Neutrophils enzymatically destroy bone (<span>[[Fig. 23-2|Figure 23-2]]</span>).
<blockquote style="color: blue; "><i>P. aeruginosa</i> osteomyelitis: puncture of foot through rubber footwear</blockquote></li><ol type="a"> <li>Devitalized bone is called sequestra.</li><li>Chronic disease produces reactive bone formation in periosteum.</li><ul> <li>Called involucrum</li> </ul><li>Draining sinus tracts to the skin surface often occur.
<blockquote style="color: blue; ">Sequestra: devitalized bone</blockquote></li><ul> <li>Danger of squamous cell carcinoma developing at orifice of sinus tract
<blockquote style="color: blue; ">Involucrum: reactive bone formation in periosteum</blockquote></li> </ul> </ol><li>Clinical findings</li><ul> <li>Fever, bone pain
<blockquote style="color: blue; ">Draining sinuses: danger of squamous cancer</blockquote></li> </ul><li>Diagnosis</li><ol type="a"> <li>Bone biopsy for culture</li><li>Imaging studies: CT scan or MRI</li> </ol><li>Treatment</li><ol type="a"> <li>Surgical débridement</li><li><i>Staphylococcus aureus</i>: vancomycin + ceftazidime</li><li><i>Salmonella paratyphi</i> (sickle cell): ciprofloxacin</li> </ol> </ol>
</div></html>
<html><a name="HC023006"></a> <br><a name="P023005"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Osteoporosis: most common metabolic abnormality of bone</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common metabolic abnormality of bone</li><li>Loss of both organic bone matrix and minerals</li><ul> <li>(1) Decreased bone mass and density</li><ul> <li>Radiograph shows osteopenia (washed out appearance).
<blockquote style="color: blue; ">Osteoporosis: loss of mineralized bone + organic bone matrix (osteoid)</blockquote></li> </ul><li>(2) Decreased thickness of cortical and trabecular bone</li> </ul><li>More common in women than men</li><ul> <li>Men have greater bone mass to begin with; takes longer to develop osteoporosis</li> </ul><li>Osteoporosis-related fractures: 50% in women > 65 years old
<blockquote style="color: blue; ">Osteoporosis: more common in women than men</blockquote></li><li>Osteoporosis-related fractures: 20% in men > 65 years old</li><li>Classification</li><ul> <li>(1) Primary</li><ul> <li>(a) Most common type (80% women, 60% men)</li><li>(b) Idiopathic type in children and young adults</li><li>(c) Postmenopausal type (most common)</li><li>(d) Senile type in men and women</li> </ul><li>(2) Secondary
<blockquote style="color: blue; ">Secondary causes: ↑ cortisol, heparin, hypogonadism, malnutrition, space travel</blockquote></li><ul> <li>(a) Underlying disease (e.g., hypercortisolism)</li><li>(b) Drugs (e.g., heparin)</li><li>(c) Hypogonadism (e.g., hypopituitarism)</li><li>(d) Malnutrition (e.g., anorexia nervosa)</li><li>(e) Space travel</li><ul> <li>Lack of gravity reduces bone stress.</li> </ul> </ul> </ul> </ol><li>Postmenopausal osteoporosis
<blockquote style="color: blue; ">Estrogen: inhibits production of osteoclasts; enhances osteoblasts</blockquote></li><ol type="a"> <li>Due to estrogen deficiency</li><ul> <li>(1) Increased resorption of bone by osteoclasts
<blockquote style="color: blue; ">↓ Estrogen: ↑ osteoclastic activity, ↓ osteoblastic activity</blockquote></li><li>(2) Decreased formation of bone by osteoblasts</li> </ul><li>Clinical findings</li><ul> <li>(1) Compression fractures of vertebral bodies (<span>[[Fig. 23-3|Figure 23-3]]</span>)
<blockquote style="color: blue; ">Postmenopausal osteoporosis: compression vertebral fractures most common</blockquote></li><ul> <li>Most common fracture</li> </ul><li>(2) Colles' fracture of distal radius</li><li>(3) Dowager's hump (<span>[[Fig. 23-4|Figure 23-4]]</span>)</li> </ul><li>Dual-photon absorptiometry</li><ul> <li>Noninvasive test that evaluates bone density
<blockquote style="color: blue; ">Diagnosis osteoporosis: dual photon absorptiometry</blockquote></li> </ul><li>Prevention</li><ul> <li>(1) Role of estrogen replacement is being reevaluated.</li><li>(2) Calcium and vitamin D supplements</li><li>(3) Stop smoking (inhibits osteoblast activity)
<blockquote style="color: blue; ">Prevention: weight-bearing exercises; calcium, vitamin D; stop smoking</blockquote></li><li>(4) Weight-bearing exercise</li><ul> <li>(a) Weight lifting; vigorous walking</li><li>(b) Excludes swimming, which decreases bone stress</li> </ul> </ul><li>Treatment
<blockquote style="color: blue; ">Rx for osteoporosis: bisphosphonates first-line drug</blockquote></li><ul> <li>(1) Bisphosphonates inhibit bone resorption.</li><ul> <li>First-line treatment</li> </ul><li>(2) Calcitonin inhibits osteoclasts.</li> </ul> </ol><li>Senile osteoporosis</li><ul> <li>Decreased ability of osteoblasts to divide and produce osteoid</li> </ul> </ol>
</div></html>
<html><a name="HC023007"></a> <br><a name="P023006"></a><div class="PA" style="color: black; "><ol type="1"> <li>Disruption of microcirculation causes bone infarctions.</li><ol type="a"> <li>The term "avascular" is sometimes used because the problem involves the blood supply to the bone.
<blockquote style="color: blue; ">Aseptic necrosis: disruption of microcirculation causes bone infarctions</blockquote></li><li>Causes</li><ul> <li>(1) Corticosteroids (35%)
<blockquote style="color: blue; ">Aseptic necrosis: most common metabolic abnormality of bone</blockquote></li><li>(2) Alcohol (22%)</li><li>(3) Other causes (43%)</li><ul> <li>(a) Idiopathic</li><li>(b) Fractures</li> </ul> </ul><li>Sites of aseptic necrosis
<blockquote style="color: blue; ">Aseptic necrosis: femoral head most common site</blockquote></li><ul> <li>(1) Femoral head and condyle</li><li>(2) Humeral head
<blockquote style="color: blue; ">Aseptic necrosis: corticosteroids most common cause</blockquote></li><li>(3) Scaphoid (navicular) and lunate bones in wrist</li><li>(4) Talus bone</li><ul> <li>Located between the calcaneus and the tibia and fibula</li> </ul> </ul><li>Femoral head aseptic necrosis</li><ul> <li>(1) Fracture in elderly persons</li><ul> <li>(a) Pertrochanteric fracture (<span>[[Fig. 23-5A|Figure 23-5]]</span>) is extracapsular and does <i>not</i> compromise blood supply to the femoral head; hence, no aseptic necrosis.
<blockquote style="color: blue; ">Aseptic necrosis: subcapsular fracture disrupts blood supply</blockquote></li><li>(b) Subcapsular fracture (<span>[[Fig. 23-5B|Figure 23-5]]</span>) disrupts blood supply (retinacular arteries from medial circumflex femoral artery); hence, aseptic necrosis occurs.</li> </ul><li>(2) Sickle cell disease (due to vasoocclusive disease; refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li><li>(3) Long-term use of corticosteroids</li> </ul><li>Scaphoid bone
<blockquote style="color: blue; ">Scaphoid bone: most common wrist bone fractured; susceptible to aseptic necrosis</blockquote></li><ul> <li>(1) Located on the thumb side of the wrist</li><li>(2) Most common bone in the wrist that is fractured</li><li>(3) Normally has a poor blood supply</li> </ul><li>Digits</li><ul> <li>Dactylitis in sickle cell anemia (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Asymptomatic
<blockquote style="color: blue; ">Aseptic necrosis: localized pain</blockquote></li><li>Localized pain exacerbated by movement</li><li>Functional limitation of activity</li> </ol><li>Bone shows increased density on radiographs (<span>[[Fig. 23-6|Figure 23-6]]</span>).</li><ol type="a"> <li>Magnetic resonance imaging</li><ul> <li>(1) Early finding-margin of low signal and inner border of high signal produce a "double line sign."
<blockquote style="color: blue; ">Aseptic necrosis: MRI most sensitive early test for aseptic necrosis</blockquote></li><li>(2) Most sensitive test (75-100%) for early detection of aseptic necrosis</li> </ul><li>CT scan</li><ul> <li>Shows central necrosis and area of collapse before regular x-ray</li> </ul><li>Bone scan</li><ul> <li>(1) Early-shows no uptake (cold area; sensitivity 70%)</li><li>(2) Later-increased uptake (result of bone remodeling)</li> </ul><li>X-ray study</li><ul> <li>(1) Most insensitive test in early phases</li><li>(2) Early-may show osteopenia (radiolucency)</li><li>(3) Later-flattening, collapsed bone</li> </ul><li>Treatment
<blockquote style="color: blue; ">Osteochondrosis: aseptic necrosis of ossification centers</blockquote></li><ul> <li>Core decompression; bone graft; joint replacement</li> </ul> </ol><li>Osteochondrosis</li><ol type="a"> <li>Aseptic necrosis of ossification centers in children</li><li>Legg-Calvé-Perthes disease
<blockquote style="color: blue; ">Legg-Calvé-Perthes disease: aseptic necrosis of femoral head ossification center</blockquote></li><ul> <li>(1) Aseptic necrosis involving the femoral head ossification center</li><li>(2) Occurs most often in boys 3 to 10 years of age</li><li>(3) Presents with pain in the knee or a limp</li><li>(4) Secondary osteoarthritis is common.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC023008"></a> <br><a name="P023007"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Osteochondritis dissecans: variant of osteochondrosis limited to articular epiphysis</blockquote>
<ol type="1"> <li>Variant of osteochondrosis limited to the articular epiphysis</li><ol type="a"> <li>Articular epiphyses fail as a result of compression.</li><li>Trauma is the primary insult.</li><li>Ischemia is a secondary injury.
<blockquote style="color: blue; ">Osteochondritis dissecans: trauma primary insult; ischemia secondary injury</blockquote></li><li>Portion of cartilage and underlying subchondral bone separates.</li> </ol><li>Occurs between 10 and 50 years of age</li><li>No sex predilection</li><li>Most common joint is knee.
<blockquote style="color: blue; ">Osteochondritis dissecans: distal femur most common site</blockquote></li><ol type="a"> <li>Lateral surface of the medial femoral condyle is the most frequent site.</li><li>Cartilage may become detached.</li> </ol><li>Other sites</li><ol type="a"> <li>Capitellum of humerus</li><li>Dome of talus bone in foot</li><li>Shoulder, hip, elbow</li> </ol><li>Clinical findings</li><ol type="a"> <li>Localized pain, stiffness, swelling</li><li>Locking of joint by loose body</li><li>Tenderness at site of lesion</li> </ol><li>Complication</li><ul> <li>Osteoarthritis
<blockquote style="color: blue; ">Osteochondritis dissecans: osteoarthritis late complication</blockquote></li> </ul><li>Diagnosis</li><ol type="a"> <li>Imaging studies used depend on the site involved.</li><li>X-ray; spiral (helical CT); MRI</li> </ol><li>Treatment</li><ol type="a"> <li>Ice after exercise</li><li>NSAIDs for pain</li><li>Immobilization</li><li>Arthroscopic surgery</li> </ol> </ol>
</div></html>
<html><a name="HC023009"></a> <br><a name="P023008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Affects physically active boys 11 to 15 years of age</li><li>Painful swelling of tibial tuberosity
<blockquote style="color: blue; ">Osgood-Schlatter disease: painful swelling tibial tuberosity in boys</blockquote></li><ul> <li>Inflammation of proximal tibial apophysis at insertion of patellar tendon</li> </ul><li>Clinical findings</li><ol type="a"> <li>Pain aggravated by</li><ul> <li>(1) Squatting</li><li>(2) Walking upstairs</li><li>(3) Extending knee with resistance</li> </ul><li>Permanent knobby-appearing knees
<blockquote style="color: blue; ">Osgood-Schlatter disease: permanent knobby-appearing knees</blockquote></li> </ol><li><i>No</i> effect on bone growth</li><li>Treatment</li><ol type="a"> <li>Ice after exercise</li><li>NSAIDs for pain</li><li>Knee splint 2 to 4 weeks in resistant cases</li> </ol> </ol>
</div></html>
<html><a name="HC023010"></a> <br><a name="P023009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Primarily occurs in men > 50 years of age
<blockquote style="color: blue; ">Paget's disease: primarily occurs in men > 50 years old; ? viral etiology</blockquote></li><li>Cause unknown (? virus-slow virus, respiratory syncytial virus)</li><li>Targets the pelvis, skull (enlarged), and femur</li> </ol><li>Pathogenesis
<blockquote style="color: blue; ">Paget's disease: osteoclastic phase followed by an osteoblastic phase</blockquote></li><ol type="a"> <li>Early phase of osteoclastic resorption of bone</li><ul> <li>Causes shaggy-appearing lytic lesions</li> </ul><li>Late phase of increased osteoblastic bone formation</li><ul> <li>(1) Markedly increased serum alkaline phosphatase
<blockquote style="color: blue; ">Paget's disease: ↑ alkaline phosphatase in osteoblastic phase</blockquote></li><li>(2) Production of thick, weak bone (mosaic bone; <span>[[Fig. 23-7|Figure 23-7]]</span>)</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Bone pain is the most common complaint.
<blockquote style="color: blue; ">Paget's disease: weak, thick, vascular bone</blockquote></li><li>Headaches, hearing loss if it affects skull</li><li>Increased hat size with skull involvement</li> </ol><li>Complications</li><ol type="a"> <li>Pathologic fractures</li><li>Risk for developing osteogenic sarcomas</li><li>Risk for developing high-output heart failure (refer to <span macro="tag [[10 Heart Disorders]] [[Chapter 10]]"></span>)
<blockquote style="color: blue; ">Complications: fractures, osteogenic sarcoma, high-output heart failure</blockquote></li><ul> <li>Due to arteriovenous connections in vascular bone</li> </ul> </ol><li>Diagnosis</li><ol type="a"> <li>Radiographs show thickened bone with shaggy areas of radiolucency.</li><li>Markedly increased serum alkaline phosphatase with normal serum calcium and phosphorus</li> </ol><li>Treatment</li><ol type="a"> <li>Bisphosphonates</li><li>Calcitonin</li> </ol> </ol>
</div></html>
<html><a name="HC023011"></a> <br><a name="P023010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Skeletal developmental anomaly
<blockquote style="color: blue; ">Fibrous dysplasia: defect in osteoblastic differentiation and maturation</blockquote></li><ol type="a"> <li>Defect in bone-forming mesenchyme with replacement of medullary bone by fibrous tissue</li><ul> <li>Defect in osteoblastic differentiation and maturation
<blockquote style="color: blue; ">Fibrous dysplasia: medullary bone replaced by fibrous tissue with cyst formation</blockquote></li> </ul><li>Cysts may develop in the fibrous tissue matrix that manifests as a defect in osteoblastic differentiation and maturation.</li> </ol><li>May involve single (monostotic; 70-80%) or multiple bones (polyostotic)</li><li>No sex predilection</li><li>Occurs between 10 and 30 years of age</li><li>Most common locations</li><ol type="a"> <li>Ribs (28%)
<blockquote style="color: blue; ">Fibrous dysplasia: ribs most common site</blockquote></li><li>Femur (23%)</li><li>Tibia or craniofacial bones (10-25%)</li><ul> <li>In craniofacial bone, it produces cherubism</li> </ul><li>Humerus, vertebra</li> </ol><li>Polyostotic bone involvement is associated with Albright's syndrome.
<blockquote style="color: blue; ">Albright's syndrome: polyostotic bone involvement; café au lait spots; precocious puberty</blockquote></li><ol type="a"> <li>Café au lait spots on skin</li><li>Precocious sexual development</li> </ol><li>Clinical findings</li><ol type="a"> <li>Pain overlying the bone</li><li>Swelling of bone</li> </ol><li>Complications
<blockquote style="color: blue; ">Complications: pathologic fracture, osteogenic sarcoma, fibrosarcoma</blockquote></li><ol type="a"> <li>Risk for a pathologic fracture</li><li>Malignant degeneration in <1%</li><ul> <li>(1) Osteogenic sarcoma</li><li>(2) Fibrosarcoma</li> </ul> </ol><li>Diagnose with imaging studies.</li><li>Treatment is surgery.</li> </ol>
</div></html>
<html><a name="HC023012"></a> <br><a name="P023011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Metastasis is the most common malignancy of bone (see Figs. 8-7A to D).
<blockquote style="color: blue; ">Metastasis: most common bone malignancy</blockquote></li><ul> <li>Breast cancer is the most common primary site.</li> </ul><li>Primary malignant tumors of bone, in descending order of frequency</li><ul> <li>Multiple myeloma, osteogenic sarcoma, chondrosarcoma, Ewing's sarcoma</li> </ul><li>Treatment for primary bone tumors is surgery.
<blockquote style="color: blue; ">Osteochondroma: most common benign bone tumor</blockquote></li><li>Summary of bone tumors (<span>[[Table 23-1|Table 23-1. TUMORS OF BONE]]</span>; see <span>[[Fig. 8-1F|Figure 8-1]]</span>)</li> </ol>
</div></html>
<html><a name="HC023014"></a> <br><a name="P023019"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Giant cell tumor: epiphysis distal femur, proximal tibia</blockquote>
<ol type="1"> <li>Routine studies</li><ul> <li>WBC count and differential, crystal analysis, mucin clot, culture, Gram stain</li> </ul><li>Crystal identification</li><ol type="a"> <li>Monosodium urate (MSU)
<blockquote style="color: blue; ">MSU crystals: negative birefringence (yellow when parallel to slow ray)</blockquote></li><ul> <li>(1) Needle-shaped (monoclinic) crystal</li><li>(2) Special polarization shows negative birefringence.</li><ul> <li>Crystal is yellow when parallel to the slow ray (<span>[[Fig. 23-8|Figure 23-8]]</span>).</li> </ul> </ul><li>Calcium pyrophosphate
<blockquote style="color: blue; ">Calcium pyrophosphate: positive birefringence (blue when parallel to slow ray)</blockquote></li><ul> <li>(1) Monoclinic-like or triclinic (rhomboid) crystals</li><li>(2) Special polarization shows positive birefringence.</li><ul> <li>Crystal is blue when parallel to the slow ray.</li> </ul> </ul><li>Mucin clot</li><ul> <li>(1) Evaluates joint viscosity</li><li>(2) Acid added to synovial clots hyaluronic acid</li><ul> <li>Hyaluronic acid is the normal joint lubricant</li> </ul><li>(3) Poor clot formation reflects decreased hyaluronic acid</li><ul> <li>Sign of joint inflammation</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC023015"></a> <br><a name="P023020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Group I
<blockquote style="color: blue; ">Group I: noninflammatory; osteoarthritis, neuropathic joint</blockquote></li><ol type="a"> <li>Noninflammatory</li><li>Examples-osteoarthritis, neuropathic joint</li> </ol><li>Group II
<blockquote style="color: blue; ">Group II: inflammatory; rheumatoid arthritis, gout</blockquote></li><ol type="a"> <li>Inflammatory</li><li>Examples-rheumatoid arthritis, gout</li> </ol><li>Group III
<blockquote style="color: blue; ">Group III: septic; Lyme disease, disseminated gonococcemia</blockquote></li><ol type="a"> <li>Septic</li><li>Examples-Lyme disease, disseminated gonococcemia</li> </ol><li>Group IV
<blockquote style="color: blue; ">Group IV: hemorrhage; trauma, hemophilia</blockquote></li><ol type="a"> <li>Hemorrhagic</li><li>Examples-trauma, hemophilia A and B</li> </ol> </ol>
</div></html>
<html><a name="HC023016"></a> <br><a name="P023021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Arthralgia is a general term for joint pain.</li><li>Arthritis connotes pain associated with joint swelling, tenderness, warmth</li><li>Morning stiffness
<blockquote style="color: blue; ">Morning stiffness: RA, SLE, polymyalgia rheumatica</blockquote></li><ol type="a"> <li>Pain in the joints that lasts >30 minutes</li><li>Characteristic finding in</li><ul> <li>(1) Rheumatoid arthritis (RA)</li><li>(2) Polymyalgia rheumatica</li><li>(3) Systemic lupus erythematosus (SLE)</li> </ul> </ol><li>Abnormal joint mobility</li><ol type="a"> <li>Due to damage to ligaments/joint capsule</li><li>Example-tear of anterior cruciate ligament</li> </ol><li>Swelling of the joint (effusion)
<blockquote style="color: blue; ">Joint effusion: blood, exudate</blockquote></li><ol type="a"> <li>Due to due increased joint fluid</li><li>Examples-exudate, blood</li> </ol><li>Redness and warmth of the joint</li><ol type="a"> <li>Sign of acute inflammation
<blockquote style="color: blue; ">Hot joint: acute inflammation; septic arthritis</blockquote></li><li>Example-septic arthritis</li> </ol><li>Joint crepitus with motion</li><ol type="a"> <li>Crackling feeling when moving a joint
<blockquote style="color: blue; ">Joint crepitus: crackling feeling; osteoarthritis</blockquote></li><li>Example-osteoarthritis</li> </ol> </ol>
</div></html>
<html><a name="HC023017"></a> <br><a name="PB023001"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Ochronosis (alkaptonuria)</b> is an autosomal recessive (AR) disease caused by deficiency of homogentisic acid oxidase and accumulation of homogentisic acid (urine turns black when oxidized). Homogentisic acid deposits in the intervertebral disks, causing osteoarthritis and other systemic findings.
<blockquote style="color: blue; ">Alkaptonuria: homogentistic acid deposits in intervertebral disks; black color</blockquote></div><a name="P023022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology
<blockquote style="color: blue; ">Osteoarthritis: most common disabling joint disease</blockquote></li><ol type="a"> <li>Noninflammatory joint disease</li><li>No sex predilection</li><li>Almost universal >65 years of age</li><li>Secondary causes</li><ul> <li>(1) Legg-Calvé-Perthes disease</li><li>(2) Osteochondritis dissecans</li><li>(3) Obesity, trauma, neuropathic joint</li><li>(4) Meniscus injuries, hemochromatosis</li> </ul><li>Common sites</li><ul> <li>(1) Femoral head, knee
<blockquote style="color: blue; ">OA: femoral head, knee, cervical/lumbar vertebrae, hands</blockquote></li><li>(2) Cervical and lumbar vertebrae</li><li>(3) Hands (usually genetic)</li> </ul><li>Less common sites</li><ul> <li>(1) Shoulder</li><li>(2) Elbow</li><li>(3) Feet with exception of first metatarsophalangeal joint
<blockquote style="color: blue; ">Ochronosis: AR; deficiency homogentisic acid; osteoarthritis</blockquote></li><ul> <li>Site for bunion formation</li> </ul> </ul> </ol><li>Progressive degeneration of articular cartilage</li><ol type="a"> <li>Primarily targets weight-bearing joints</li><li>Components of articular cartilage
<blockquote style="color: blue; ">Articular cartilage: proteoglycans, type II collagen</blockquote></li><ul> <li>(1) Proteoglycans that provide elasticity</li><li>(2) Type II collagen that provides tensile strength</li> </ul><li>Cytokines activate metalloproteinases
<blockquote style="color: blue; ">OA: wearing down of articular cartilage; bone rubs on bone</blockquote></li><ul> <li>Causes degradation of proteoglycans and collagen</li> </ul><li>Joint findings (<span>[[Fig. 23-9|Figure 23-9]]</span>)</li><ul> <li>(1) Erosion and clefts in articular cartilage</li><li>(2) Reactive bone formation at joint margins (osteophytes)
<blockquote style="color: blue; ">OA: osteophytes at joint margins</blockquote></li><ul> <li>Causes a slight increase in serum alkaline phosphatase</li> </ul><li>(3) Subchondral cysts
<blockquote style="color: blue; ">OA: clefts, subchondral cysts</blockquote></li><li>(4) Bone eventually rubs on bone.</li><ul> <li>Produces dense, sclerotic bone</li> </ul><li>(5) <i>No</i> ankylosis (fusion) of the joint
<blockquote style="color: blue; ">OA: no fusion of the joint</blockquote></li><li>(6) Joint mice</li><ul> <li>Fragments of articular cartilage that break free into the joint space</li> </ul> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Pain is the most common complaint</li><ul> <li>(1) Osteophytes irritating synovial lining; bone rubbing on bone
<blockquote style="color: blue; ">OA: pain most common complaint</blockquote></li><li>(2) Hip OA may refer pain to the groin</li> </ul><li>Joint stiffness after inactivity</li><ul> <li>(1) Waking up in morning</li><li>(2) After sitting
<blockquote style="color: blue; ">OA: joint stiffness after inactivity</blockquote></li><li>(3) Aggravated by activity</li> </ul><li>Hand involvement (<span>[[Fig. 23-10|Figure 23-10]]</span>)</li><ul> <li>(1) Enlargement of distal interphalangeal joints (DIPs)</li><ul> <li>Called Heberden's nodes (osteophytes)
<blockquote style="color: blue; ">OA fingers: Heberden's nodes; DIP joint enlargement/pain</blockquote></li> </ul><li>(2) Enlargement of proximal interphalangeal joints (PIPs)</li><ul> <li>Called Bouchard's nodes (osteophytes)</li> </ul> </ul><li>Pain with passive motion of the joint
<blockquote style="color: blue; ">OA fingers: Bouchard's nodes; PIP joint enlargement/pain</blockquote></li><ul> <li>Due to secondary synovitis</li> </ul><li>Vertebral findings</li><ul> <li>Degenerative disk disease and compressive neuropathies</li> </ul> </ol><li>Diagnosis
<blockquote style="color: blue; ">OA vertebral column: cervical/lumbar; degenerative disk disease, compressive neuropathies</blockquote></li><ul> <li>Imaging studies</li> </ul><li>Treatment</li><ol type="a"> <li>Heat; decrease weight bearing; range of motion exercises</li><li>Use of a cane</li><li>Analgesics (NSAIDs, acetaminophen)</li><li>Viscosupplementation</li><ul> <li>Oral chondroitin sulfate, glucosamine</li> </ul><li>Joint replacement</li> </ol> </ol>
</div></html>
<html><a name="HC023018"></a> <br><a name="P023023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Noninflammatory joint disease</li><li>Secondary to a neurologic disease</li><ul> <li>Loss of proprioception and deep sensation leading to recurrent trauma
<blockquote style="color: blue; ">Neuropathic joint: loss of proprioception, deep sensation leading to recurrent trauma</blockquote></li> </ul><li>Causes</li><ol type="a"> <li>Diabetes mellitus (15%)</li><ul> <li>Primarily affects the tarsometatarsal joint</li> </ul><li>Syringomyelia (20-25%)
<blockquote style="color: blue; ">Common causes: diabetes, syringomyelia, tabes dorsalis</blockquote></li><ul> <li>Primarily affects the shoulder, elbow, wrist joints</li> </ul><li>Tabes dorsalis (10-20%)</li><ul> <li>Primarily affects the hip, knee, ankle joints</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Immobilization</li><li>Pneumatic walking braces</li> </ol> </ol>
</div></html>
<html><a name="HC023019"></a> <br><a name="P023024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Occurs more often in women 30 to 50 years of age</li><li>HLA-DR4 association</li><li>? Initial inciting agents</li><ul> <li>Epstein-Barr virus, parvovirus, human herpesvirus 6, <i>Mycoplasma</i>
<blockquote style="color: blue; ">RA: B cells produce RF, an IgM antibody with specificity against Fc portion of IgG</blockquote></li> </ul> </ol><li>Pathogenesis of joint disease is unclear; key points:</li><ol type="a"> <li>B and T cells are activated leading to damage of synovial cells</li><li>Synovial cells express an antigen that triggers B cells to produce rheumatoid factor (RF).</li><li>RF is an IgM autoantibody that has specificity for the Fc portion of IgG.
<blockquote style="color: blue; ">RA: RF combines with IgG to produce immunocomplexes that activate the complement system</blockquote></li><li>RF and IgG join together to form immunocomplexes (type III hypersensitivity).</li><li>Immunocomplexes activate the complement system to produce C5a, a chemotactic agent for neutrophils and other leukocytes to enter the joint space.</li><li>Chronic synovitis and pannus formation eventually occur (<span>[[Fig. 23-11|Figure 23-11]]</span>).</li><li>Pannus is granulation tissue that is formed within the synovial tissue by fibroblasts and inflammatory cells (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>).
<blockquote style="color: blue; ">Pannus (granulation tissue): releases cytokines that destroy articular cartilage</blockquote></li><li>Pannus proliferates and releases cytokines that eventually destroy the articular cartilage leading to fusion of the joint by scar tissue (called ankylosis).
<blockquote style="color: blue; ">Repair by fibrosis causes fusion of the joint (ankylosis)</blockquote></li> </ol><li>Clinical findings</li><ol type="a"> <li>Symmetric involvement of second/third metacarpophalangeal (MCP) and PIP joints</li><ul> <li>(1) Produces ulnar deviation, morning stiffness (<span>[[Fig. 23-12|Figure 23-12]]</span>)</li><li>(2) Swan neck deformity
<blockquote style="color: blue; ">RA hand: involves MCP and PIP joints; bilateral ulnar deviation</blockquote></li><ul> <li>(a) Flexion of DIP joint</li><li>(b) Extension of PIP joint</li> </ul><li>(3) Boutonnière deformity</li><ul> <li>(a) Extension of DIP joint</li><li>(b) Flexion of PIP joint</li> </ul><li>(4) Other joints commonly involved</li><ul> <li>(a) Knees, cervical spine, hips</li><li>(b) Shoulders, elbows</li> </ul> </ul><li>Lung disease
<blockquote style="color: blue; ">RA lung: interstitial fibrosis, effusions</blockquote></li><ul> <li>Chronic pleuritis with effusions, interstitial fibrosis</li> </ul><li>Hematologic disease</li><ul> <li>(1) Anemia of chronic disease (ACD)
<blockquote style="color: blue; ">RA blood: ACD, AIHA, Felty's syndrome (autoimmune neutropenia, splenomegaly)</blockquote></li><li>(2) Felty's syndrome</li><ul> <li>Autoimmune neutropenia and splenomegaly</li> </ul><li>(3) Autoimmune hemolytic anemia (AIHA)</li> </ul><li>Carpal tunnel syndrome (see section V)</li><ul> <li>Entrapment of median nerve under transverse carpal ligament</li> </ul><li>Cervical spine</li><ul> <li>(1) Entire cervical spine is frequently involved
<blockquote style="color: blue; ">RA cervical spine: subluxation atlantoaxial joint; cord/vertebral artery compression</blockquote></li><li>(2) Subluxation of atlantoaxial joint particularly dangerous</li><ul> <li>(a) Possible compression of spinal cord</li><li>(b) Possible compression of vertebral artery causing stroke</li> </ul> </ul><li>Rheumatoid nodules
<blockquote style="color: blue; ">Caplan syndrome: rheumatoid nodules in lung plus pneumoconiosis</blockquote></li><ul> <li>(1) Extensor surface of the forearm, lungs</li><li>(2) Fibrinoid necrosis present in center of nodule (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li><li>(3) Correlates with very high titers of RF</li> </ul><li>Cardiovascular disease</li><ul> <li>(1) Fibrinous pericarditis</li><li>(2) Aortitis
<blockquote style="color: blue; ">RA cardiovascular: pericarditis, aortitis, vasculitis</blockquote></li><li>(3) Immunocomplex vasculitis</li><ul> <li>(a) Located around the ankles</li><li>(b) Correlates with high RF titers</li> </ul> </ul><li>Popliteal (Baker's) cyst behind the knee joint</li><ul> <li>(1) Outpouching of synovial sack into the posterior joint space due to increased intra-articular pressure
<blockquote style="color: blue; ">Baker's cyst: outpouching of posterior joint space in knee</blockquote></li><li>(2) Sometimes ruptures and dissects into the calf</li><ul> <li>Frequently misdiagnosed as deep venous thrombosis (DVT)</li> </ul><li>(3) Sometimes confused with popliteal artery aneurysm</li><ul> <li>Ultrasound easily makes the distinction.</li> </ul> </ul> </ol><li>Laboratory findings in RA</li><ol type="a"> <li>Positive serum antinuclear antibody (ANA) test (30%)</li><li>Positive serum RF (70-90%)</li><li>Normal to increased serum C3
<blockquote style="color: blue; ">RA lab: + serum RF, ANA</blockquote></li><li>Decreased synovial C3</li><li>Increased serum total protein</li><ul> <li>(1) Due to increase in γ-globulins (IgG) in chronic inflammation</li><li>(2) Polyclonal gammopathy on serum protein electrophoresis (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>)</li> </ul> </ol><li>Diagnosis</li><ul> <li>Laboratory tests are listed in previous section.</li> </ul><li>Treatment</li><ol type="a"> <li>Physical therapy emphasizing movement of joints</li><ul> <li>Swimming pool exercises are very useful.</li> </ul><li>Initial treatment with NSAIDS</li><li>Early treatment with disease-modifying drugs</li><ul> <li>(1) Minimizes long-term joint damage</li><li>(2) Methotrexate (most commonly used agent)</li><li>(3) Cyclosporine; corticosteroids; hydroxychloroquine; gold compounds</li><li>(4) Tumor necrosis factor (TNF)-α blockers effective if disease-modifying drugs ineffective</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC023020"></a> <br><a name="P023025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Female dominant autoimmune disease
<blockquote style="color: blue; ">Sjögren's syndrome: destruction minor salivary glands and lacrimal glands</blockquote></li><li>Pathogenesis</li><ul> <li>Autoimmune destruction of minor salivary glands and lacrimal glands</li> </ul><li>Clinical findings</li><ol type="a"> <li>Rheumatoid arthritis</li><li>Keratoconjunctivitis sicca</li><ul> <li>(1) Dry eyes described as "sand in my eyes"</li><li>(2) Due to autoimmune destruction of lacrimal glands</li> </ul><li>Xerostomia or dry mouth</li><ul> <li>(1) Autoimmune destruction of minor salivary glands</li><ul> <li>"Doctor, I can't swallow dry crackers."
<blockquote style="color: blue; ">Sjögren's syndrome: dry eyes; dry mouth</blockquote></li> </ul><li>(2) Dental caries</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Positive serum ANA in most cases</li><li>Positive serum RF (90%)</li><li>Anti-SS-A antibodies (Ro; 70-95%)</li><li>Anti-SS-B antibodies (La; 60-90%)</li> </ol><li>Confirm with lip biopsy</li><ul> <li>Must demonstrate lymphoid destruction of minor salivary glands
<blockquote style="color: blue; ">Lab: + serum ANA, RF, anti-SS-A/anti-SS-B; lip biopsy confirms</blockquote></li> </ul><li>Treatment</li><ol type="a"> <li>Artificial tears</li><li>Pilocarpine or cyclosporine eye drops</li><li>Cevimeline (cholinergic agent with muscarinic agonist activity</li><ul> <li>Used for dry mouth</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC023021"></a> <br><a name="P023026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Occurs in children < 16 years of age</li><li>More common in girls
<blockquote style="color: blue; ">JRA: RF is usually negative</blockquote></li><li>RF is usually absent.</li> </ol><li>Still's disease (20% of cases)</li><ol type="a"> <li>Commonly presents as an "infectious disease"</li><li>Fever, rash, polyarthritis
<blockquote style="color: blue; ">JRA, Still's disease: fever, rash, polyarthritis</blockquote></li><li>Generalized lymphadenopathy</li><li>Neutrophilic leukocytosis</li> </ol><li>Polyarticular JRA (40% of cases)
<blockquote style="color: blue; ">JRA, polyarticular: disabling arthritis predominates</blockquote></li><ul> <li>Disabling arthritis predominates.</li> </ul><li>Pauciarticular JRA (40% of cases)</li><ol type="a"> <li>Arthritis limited to a few joints.
<blockquote style="color: blue; ">JRA, pauciarticular: limited arthritis; uveitis and potential for blindness</blockquote></li><li>Uveitis with the potential for blindness</li> </ol> </ol>
</div></html>
<html><a name="HC023022"></a> <br><a name="P023027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Occurs more often in men > 30 years of age (95%)</li><li>Uncommon in women before menopause (5%)
<blockquote style="color: blue; ">Gout: male dominant disease</blockquote></li><li>Primary gout arises from inborn errors of metabolism involving purine metabolism.</li><ul> <li>Example-deficiency of hypoxanthine-guanine phosphoryltransferase (HGPRT) in Lesch-Nyhan syndrome (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li> </ul><li>Secondary causes are more common causes of gout.
<blockquote style="color: blue; ">Gout: most cases due to underexcretion of uric acid</blockquote></li><ul> <li>(1) Underexcretion of uric acid in kidneys (80-90%)</li><ul> <li>Examples-lead poisoning; alcoholism; diets rich in red meat, seafood, beer</li> </ul><li>(2) Overproduction of uric acid (increased nucleated cell turnover; 10-20%)</li><ul> <li>Examples-treating leukemia; psoriasis</li> </ul> </ul><li>Clinical conditions commonly associated with gout</li><ul> <li>(1) Urate nephropathy, renal stones (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)
<blockquote style="color: blue; ">Gout associations: urate nephropathy, renal stones, hypertension, artery disease, Pb poisoning</blockquote></li><li>(2) Hypertension, coronary artery disease</li><li>(3) Lead poisoning</li><ul> <li>Produces interstitial nephritis, which interferes with uric acid excretion</li> </ul> </ul> </ol><li>Recurrent acute attacks of gout are the rule.</li><ol type="a"> <li>Most commonly involve the first metatarsophalangeal joint (called podagra)</li><li>Often precipitated by dietary indiscretions, illness, exercise, emotional stress
<blockquote style="color: blue; ">Acute gout: 1st metatarsophalangeal joint most often involved</blockquote></li><li>Free uric acid crystals in the synovial fluid are proinflammatory.</li><ul> <li>(1) Activate synovial cells, leukocytes, and the complement cascade, the latter releasing C5a, which attracts neutrophils into the joint producing acute inflammation</li><ul> <li>Neutrophils also phagocytose uric acid crystals.
<blockquote style="color: blue; ">Acute gout: free uric acid crystals responsible for initiating the attack</blockquote></li> </ul><li>(2) Another common site for acute gout is the extensor tenosynovium on the dorsum of the midfoot</li> </ul><li>Clinical findings acute gout</li><ul> <li>(1) Sudden onset of severe pain in the big toe</li><li>(2) Joint is hot, red, and swollen (<span>[[Fig. 23-13|Figure 23-13]]</span>).</li><li>(3) Fever, tachycardia, and other constitutional signs</li> </ul><li>Laboratory findings</li><ul> <li>(1) Hyperuricemia</li><ul> <li>(a) Increased serum uric acid > 7 mg/dL in men</li><li>(b) Increased serum uric acid > 6 mg/dL in women</li> </ul><li>(2) Absolute neutrophilic leukocytosis
<blockquote style="color: blue; ">Acute gout: must confirm with joint aspiration; hyperuricemia does <i>not</i> define gout</blockquote></li><li>(3) Joint aspiration is confirmatory.</li><ul> <li>Negatively birefringent MSU crystals</li> </ul> </ul> </ol><li>Chronic gout</li><ol type="a"> <li>Chronic gout is likely to occur if gout is poorly controlled.
<blockquote style="color: blue; ">Tophus: MSU deposits in soft tissue around the joint</blockquote></li><li>Uric acid crystals accumulate in the joint and produce a tophus.</li><ul> <li>(1) Due to MSU crystals leaking into the soft tissue around the joint (<span>[[Fig. 23-14|Figure 23-14]]</span>)</li><li>(2) MSU excites a brisk granulomatous reaction in the periarticular tissue.</li><ul> <li>Microscopic sections reveal numerous multinucleated giant cells within which are MSU crystals that polarize.</li> </ul> </ul><li>Tophi destroy subjacent bone causing erosive arthritis.</li> </ol><li>Treatment</li><ol type="a"> <li>Modify diet to eliminate diets high in purine.
<blockquote style="color: blue; ">Nonpharmacologic Rx of gout: eliminate high-purine diet; moderation in alcohol intake</blockquote></li><li>Moderation in alcohol intake (refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>)</li><li>Drugs</li><ul> <li>(1) Treatment for acute gouty arthritis
<blockquote style="color: blue; ">Pharmacologic Rx of acute gout: NSAIDs or colchicine</blockquote></li><ul> <li>(a) NSAIDs or colchicine</li><li>(b) Corticosteroids if intolerant to above drugs</li> </ul><li>(2) Chronic treatment to prevent acute gout</li><ul> <li>(a) Goal is to normalize serum uric acid.
<blockquote style="color: blue; ">Drugs to prevent gout: uricosuric agents for underexcretors; allopurinol for overproducers</blockquote></li><li>(b) Uricosuric agents for underexcretors (e.g., probenecid)</li><ul> <li>If 24-hour urine collection of uric acid < 700 mg</li> </ul><li>(c) Allopurinol (xanthine oxidase inhibitor) for overproducers</li><ul> <li>If 24-hour urine collection of uric acid > 900 mg</li> </ul> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC023023"></a> <br><a name="P023028"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Deposition of calcium pyrophosphate in tissues
<blockquote style="color: blue; ">CPPD disease: deposition of calcium pyrophosphate in tissues</blockquote></li><ul> <li>(1) Deposition in cartilage (called chondrocalcinosis)</li><li>(2) Less commonly in tendons, ligaments, synovial tissue, bursa</li> </ul><li>Incidence of CPPD increases in the presence of:
<blockquote style="color: blue; ">CPPD disease: ↑ with hemochromatosis, hemosiderosis, primary HPTH</blockquote></li><ul> <li>(1) Hemochromatosis, hemosiderosis</li><ul> <li>(a) Pyrophosphate inhibitor is increased in these diseases.</li><li>(b) Causes an increase in inorganic pyrophosphate concentration</li> </ul><li>(2) Primary hyperparathyroidism (HPTH)</li><ul> <li>Increase in calcium is responsible.</li> </ul> </ul><li>Four variants are associated with the disease.</li><li>Most common variant is osteoarthritis (OA).</li><ul> <li>(1) Most common in elderly population</li><ul> <li>Present in 50% of patients who are 85 years old</li> </ul><li>(2) Degenerative arthritis with symptoms similar to OA</li><li>(3) Most common joint involved is the knee.
<blockquote style="color: blue; ">CPPD OA variant: knee most common joint; chondrocalcinosis present</blockquote></li><li>(4) Calcium pyrophosphate crystals deposit in articular cartilage (usually knee).</li><ul> <li>(a) Crystals produce linear deposits in articular cartilage (<span>[[Fig. 23-15|Figure 23-15]]</span>).</li><li>(b) Called chondrocalcinosis when it deposits in articular cartilage
<blockquote style="color: blue; ">Chondrocalcinosis: linear deposits of calcium pyrophosphate in articular cartilage</blockquote></li> </ul><li>(5) Crystals phagocytosed by neutrophils show positive birefringence.</li><li>(6) Treatment</li><ul> <li>NSAIDs; colchicine; arthroscopic surgery</li> </ul> </ul> </ol> </ol>
</div></html>
![[23.II.A.Synovial fluid (SF) analysis]]
<<tiddler [[23.II.A.Synovial fluid (SF) analysis]]>>
![[23.II.B.Classification of joint disorders]]
<<tiddler [[23.II.B.Classification of joint disorders]]>>
![[23.II.C.Signs and symptoms of joint disease]]
<<tiddler [[23.II.C.Signs and symptoms of joint disease]]>>
![[23.II.D.Osteoarthritis (OA)]]
<<tiddler [[23.II.D.Osteoarthritis (OA)]]>>
![[23.II.E.Neuropathic arthropathy (Charcot's joint)]]
<<tiddler [[23.II.E.Neuropathic arthropathy (Charcot's joint)]]>>
![[23.II.F.Rheumatoid arthritis (RA)]]
<<tiddler [[23.II.F.Rheumatoid arthritis (RA)]]>>
![[23.II.G.Sjögren's syndrome (SS)]]
<<tiddler [[23.II.G.Sjögren's syndrome (SS)]]>>
![[23.II.H.Juvenile rheumatoid arthritis (JRA)]]
<<tiddler [[23.II.H.Juvenile rheumatoid arthritis (JRA)]]>>
![[23.II.I.Gouty arthritis]]
<<tiddler [[23.II.I.Gouty arthritis]]>>
![[23.II.J.Calcium pyrophosphate dihydrate deposition (CPPD) disease]]
<<tiddler [[23.II.J.Calcium pyrophosphate dihydrate deposition (CPPD) disease]]>>
![[23.II.K.Seronegative spondyloarthropathies (spondyloarthritis)]]
<<tiddler [[23.II.K.Seronegative spondyloarthropathies (spondyloarthritis)]]>>
![[23.II.L.Septic arthritis]]
<<tiddler [[23.II.L.Septic arthritis]]>>
<html><a name="HC023024"></a> <br><a name="P023029"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Seronegative: RF negative arthritis</blockquote>
<ol type="1"> <li>Characteristics</li><ol type="a"> <li>Rheumatoid factor (RF) negative (meaning of seronegative)</li><li>Involve the axial skeleton (spondylitis)
<blockquote style="color: blue; ">Key points: - RF; + HLA-B27; male; sacroiliitis; spondylitis</blockquote></li><li>Individuals HLA-B27 positive</li><li>Male dominant</li><li>Sacroiliitis with or without peripheral arthritis</li> </ol><li>Types of spondyloarthropathy</li><ol type="a"> <li>Ankylosing spondylitis</li><li>Reiter's syndrome</li><li>Psoriasis</li><li>Enteropathic</li><ul> <li>Associated with ulcerative colitis, shigellosis</li> </ul> </ol><li>Ankylosing spondylitis (AS)</li><ol type="a"> <li>Initially targets sacroiliac joint in young men</li><ul> <li>Bilateral sacroiliitis with morning stiffness
<blockquote style="color: blue; ">AS: begins with sacroiliitis</blockquote></li> </ul><li>Eventually involves the vertebral column (<span>[[Fig. 23-16|Figure 23-16]]</span>)</li><ul> <li>(1) Fusion of vertebrae ("bamboo spine") causes forward curvature (kyphosis; <span>[[Fig. 23-17|Figure 23-17]]</span>).</li><li>(2) Kyphosis interferes with chest wall movement.</li><ul> <li>(a) Nonpulmonary restrictive lung disease
<blockquote style="color: blue; ">AS: over time develop fusion of vertebrae ("bamboo spine")</blockquote></li><li>(b) Schober test evaluates degree of restriction to forward bending.</li> </ul> </ul><li>Aortitis with aortic regurgitation</li><li>Anterior uveitis (20%)</li><ul> <li>(1) Blurry vision</li><li>(2) Potential for blindness
<blockquote style="color: blue; ">AS: aortitis; uveitis with potential for blindness</blockquote></li> </ul><li>Treatment</li><ul> <li>(1) NSAIDs</li><li>(2) Disease-modifying agents</li><ul> <li>Methotrexate, cyclosporine, corticosteroids</li> </ul><li>(3) TNF-α inhibitors</li><ul> <li>Extremely effective in slowing down progression of the disease</li> </ul> </ul> </ol><li>Reiter's syndrome
<blockquote style="color: blue; ">Reiter's syndrome: <i>C. trachomatis</i> urethritis, arthritis, conjunctivitis</blockquote></li><ol type="a"> <li>Urethritis due to <i>Chlamydia trachomatis</i></li><li>Arthritis and Achilles tendon periostitis
<blockquote style="color: blue; ">Reiter's syndrome: Achilles tendon periostitis is diagnostic sign</blockquote></li><ul> <li>Achilles tendon periostitis is a confirmatory radiologic sign.</li> </ul><li>Conjunctivitis (noninfectious)</li> </ol><li>Psoriatic arthritis</li><ol type="a"> <li>Sausage-shaped DIP joints (finger or toe)</li><li>Radiographs show erosive joint disease.
<blockquote style="color: blue; ">Psoriatic arthritis: sausage-shaped DIP joints; "pencil-in-cup" deformity</blockquote></li><ul> <li>"Pencil-in-cup" deformity (<span>[[Fig. 23-18|Figure 23-18]]</span>)</li> </ul><li>Extensive nail pitting</li> </ol> </ol>
</div></html>
<html><a name="HC023025"></a> <br><a name="P023030"></a><div class="PA" style="color: black; "><ol type="1"> <li><i>Staphylococcus aureus</i></li><ol type="a"> <li>Most common nongonococcal cause of septic arthritis</li><li>Treatment</li><ul> <li>Nafcillin + cephalosporin (third generation)</li> </ul> </ol><li><i>Neisseria gonorrhoeae</i>
<blockquote style="color: blue; "><i>Neisseria gonorrhoeae</i>: most common cause of septic arthritis in urban populations</blockquote></li><ol type="a"> <li>Most common cause of septic arthritis in urban populations</li><li>May produce disseminated gonococcemia</li><ul> <li>(1) More common in young women</li><ul> <li>Deficiency of C6-C9 predisposes to dissemination
<blockquote style="color: blue; ">Disseminated gonococcemia: septic arthritis, tenosynovitis, dermatitis</blockquote></li> </ul><li>(2) Septic arthritis (knee)</li><li>(3) Tenosynovitis (wrists and ankles)</li><li>(4) Dermatitis (pustules on wrists or ankles)</li><li>(5) Treatment is ceftriaxone.</li> </ul> </ol><li>Lyme disease
<blockquote style="color: blue; "><i>Borrelia burgdorferi</i>: gram-negative spirochete; cause of Lyme disease</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Transmitted by bite of <i>Ixodes</i> tick; <i>Borrelia burgdorferi</i> (spirochete)</li><li>(2) White-tailed deer is a reservoir for the organism.
<blockquote style="color: blue; ">Lyme disease: vector <i>Ixodes</i> tick; reservoir white-tailed deer</blockquote></li> </ul><li>Early disease</li><ul> <li>(1) Erythema chronicum migrans develops at tick bite site (<span>[[Fig. 23-19|Figure 23-19]]</span>).</li><li>(2) Red, expanding lesion with concentric circles ("bull's-eye" lesion)
<blockquote style="color: blue; ">Erythema chronicum migrans: pathognomonic of Lyme disease</blockquote></li><li>(3) Pathognomonic lesion of Lyme disease</li> </ul><li>Late disease</li><ul> <li>(1) Disabling arthritis (usually involves the knee)</li><li>(2) Bilateral Bell's palsy
<blockquote style="color: blue; ">Lyme disease: disabling arthritis, Bell's palsy, myocarditis</blockquote></li><ul> <li>Highly predictive of Lyme disease</li> </ul><li>(3) Myocarditis and pericarditis</li> </ul><li>Diagnosis</li><ul> <li>(1) ELISA (enzyme-linked immunosorbent assay) testing first as screen (highly sensitive</li><li>(2) Western blot assay for equivocal or positive ELISA test</li><ul> <li>High specificity (94-96%)</li> </ul><li>(3) PCR (polymerase chain reaction) test is also available</li> </ul><li>Treatment</li><ul> <li>(1) Adults-doxycycline or amoxicillin or erythromycin or ceftriaxone</li><li>(2) Child-amoxicillin</li> </ul><li>Babesiosis
<blockquote style="color: blue; ">Babesiosis: tick-transmitted hemolytic anemia</blockquote></li><ul> <li>(1) Intraerythrocytic protozoal disease due to <i>Babesia microti</i></li><li>(2) Secondary infection transmitted by <i>Ixodes</i></li><ul> <li>Often presents concurrently with Lyme disease</li> </ul><li>(3) Fever, headache, hemolytic anemia</li><li>(4) Diagnosis</li><ul> <li>(a) Wright- or Giemsa-stained peripheral smear to look for organisms</li><li>(b) Serologic testing</li> </ul><li>(5) Treatment</li><ul> <li>Atovaquone + azithromycin</li> </ul> </ul> </ol><li>Septic arthritis and tendinitis due to cat/dog bite
<blockquote style="color: blue; "><i>Pasteurella multocida</i>: septic arthritis/tendinitis due to cat/dog bite</blockquote></li><ol type="a"> <li>Causal agent is <i>Pasteurella multocida</i>.</li><li>Most common infection secondary to animal injury</li><li>Types of infection</li><ul> <li>(1) Cellulitis (most common)</li><li>(2) Septic arthritis/tendinitis</li><li>(3) Osteomyelitis</li><li>(4) Endocarditis, meningitis</li> </ul><li>Rapid onset of infection at the bite site (usually within 24 hours)</li><li>Treatment</li><ul> <li>Amoxicillin-clavulanate</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC023027"></a> <br><a name="P023043"></a><div class="PA" style="color: black; "><ol type="1"> <li>Innervation of the muscle determines fiber type.</li><li>Type I fibers
<blockquote style="color: blue; ">Type I: slow-twitch (red); rich in mitochondria, oxidative enzymes, poor in ATPase enzymes</blockquote></li><ol type="a"> <li>Slow-twitch (red) fibers</li><ul> <li>(1) Slow contraction but repetitive</li><li>(2) Do <i>not</i> fatigue easily</li><li>(3) Example-long muscles in the back</li> </ul><li>Rich in mitochondria, myoglobin, and oxidative enzymes</li><li>Weak in ATPase enzymes</li> </ol><li>Type II fibers</li><ol type="a"> <li>Fast-twitch (white) fibers
<blockquote style="color: blue; ">Type II: fast-twitch (white); poor in mitochondria, oxidative enzymes; rich in ATPase enzymes</blockquote></li><ul> <li>(1) Fast contraction, but fatigue easily</li><li>(2) Specialized for fine, skilled movement</li><li>(3) Examples-extraocular muscles, some muscles in the hand</li> </ul><li>Poor in mitochondria, myoglobin, oxidative enzymes</li><li>Rich in ATPase enzymes</li> </ol> </ol>
</div></html>
<html><a name="HC023028"></a> <br><a name="P023044"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Muscle weakness: motor neuron, neuromuscular synapse, muscle dysfunction</blockquote>
<ol type="1"> <li>Pathogenesis of muscle weakness</li><ol type="a"> <li>Abnormality in the motor neuron pathways</li><ul> <li>Example-poliomyelitis</li> </ul><li>Abnormality in the neuromuscular synapse</li><ul> <li>Example-myasthenia gravis</li> </ul><li>Abnormality in muscle</li><ul> <li>Example-muscular dystrophy</li> </ul> </ol><li>Neurogenic atrophy
<blockquote style="color: blue; ">Neurogenic atrophy: motor neuron or axon degenerates</blockquote></li><ol type="a"> <li>Motor neuron or its axon degenerates.</li><li>Produces atrophy of type I and II fibers</li> </ol><li><i>Trichinella spiralis</i> infection</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Causative agent <i>Trichinella spiralis</i> (nematode)</li><li>(2) Transmission</li><ul> <li>(a) Eating raw or poorly cooked pork containing the encysted larvae in muscle</li><li>(b) Common on pig farms where pigs are fed uncooked garbage
<blockquote style="color: blue; ">Trichinosis: <i>Trichinella spiralis</i> (nematode); from eating encysted larvae in pig muscle</blockquote></li><li>(c) Bear and seal meat are other sources</li><li>(d) Larva excyst and develop into adult worms within small intestine mucosa.</li><li>(e) Eggs hatch within the adult female worm.</li><li>(f) Larvae are released into the blood stream.</li><li>(g) Larvae encyst in striated muscle.
<blockquote style="color: blue; ">Trichinosis: calcified larvae visible on x-ray</blockquote></li><ul> <li>Commonly undergo dystrophic calcification; visible on x-ray</li> </ul><li>(h) Larvae die if deposited in other sites.</li> </ul> </ul><li>Trichinosis</li><ul> <li>(1) Muscle pain</li><li>(2) Periorbital edema (larva)</li><li>(3) Splinter hemorrhages in nails
<blockquote style="color: blue; ">Trichinosis: muscle pain, periorbital edema, splinter hemorrhages</blockquote></li><li>(4) Complications</li><ul> <li>Myocarditis, encephalitis</li> </ul><li>(5) Diagnosis</li><ul> <li>Pronounced eosinophilia; muscle biopsy
<blockquote style="color: blue; ">Trichinosis: pronounced eosinophilia</blockquote></li> </ul><li>(6) Treatment is albendazole.</li> </ul> </ol><li>Invasive infections due to group A streptococcus</li><ol type="a"> <li>Types of invasive infections</li><ul> <li>(1) Necrotizing fasciitis
<blockquote style="color: blue; ">Invasive group A streptococcus: necrotizing fasciitis, myositis, STSS</blockquote></li><li>(2) Myositis</li><li>(3) Streptococcal toxic shock syndrome (STSS)</li> </ul><li>Related to various toxins produced by the streptococcus</li><ul> <li>(1) Pyrogenic exotoxin A</li><ul> <li>Superantigen associated with STSS
<blockquote style="color: blue; ">Invasive group A streptococcus: exotoxin A (superantigen), exotoxin B (protease)</blockquote></li> </ul><li>(2) Exotoxin B</li><ul> <li>Protease that destroys tissue associated with necrotizing fasciitis</li> </ul> </ul><li>Treatment</li><ul> <li>(1) Intravenous penicillin G + clindamycin</li><li>(2) Intravenous immunoglobulin</li> </ul><li>Death rates range from 20% to 100%.</li> </ol><li>Duchenne's muscular dystrophy (DMD)</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) X-linked recessive (XR)</li><li>(2) Incidence 1:3500 male births</li> </ul><li>Pathogenesis</li><ul> <li>(1) Absence of dystrophin
<blockquote style="color: blue; ">DMD: XR; absence of dystrophin</blockquote></li><ul> <li>(a) Dystrophin normally anchors actin to membrane glycoprotein.</li><li>(b) Becker's type has deficiency/defective dystrophin.</li> </ul><li>(2) Most common childhood muscular dystrophy</li><li>(3) Progressive degeneration of type I and II fibers</li><li>(4) Fibrosis and infiltration of muscle tissue by fatty tissue
<blockquote style="color: blue; ">DMD: pseudohypertrophy of calf muscles</blockquote></li><ul> <li>Produces pseudohypertrophy of calf muscles (<span>[[Fig. 23-20A|Figure 23-20]]</span>)</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Symptoms occur between 2 and 5 years of age.</li><li>(2) Weakness and wasting of pelvic muscles
<blockquote style="color: blue; ">DMD: waddling gait due to weakness of pelvic muscles</blockquote></li><ul> <li>(a) Child places hands on the knees for help in standing (Gower's maneuver; <span>[[Fig. 23-20B|Figure 23-20]]</span>).</li><li>(b) Waddling gait (duck-like)</li> </ul><li>(3) Cardiac involvement may be present.</li><li>(4) Death usually occurs by 20 years of age.</li> </ul><li>Laboratory findings</li><ul> <li>(1) Serum creatine kinase (CK) is increased at birth.
<blockquote style="color: blue; ">DMD: ↑ serum CK at birth; ↓as muscles degenerate</blockquote></li><ul> <li>Progressively declines as muscle degenerates</li> </ul><li>(2) Female carriers have increased levels of serum CK.</li> </ul><li>Diagnosis</li><ul> <li>(1) Muscle biopsy</li><li>(2) DNA testing available (Western blot)</li><ul> <li>Diagnosed prenatally via chorionic villous sampling</li> </ul> </ul><li>Treatment</li><ul> <li>Corticosteroids improve muscle strength and function.</li> </ul> </ol><li>Myotonic dystrophy (MD)</li><ol type="a"> <li>Epidemiology and pathogenesis
<blockquote style="color: blue; ">MD: most common adult muscular dystrophy; CTG trinucleotide repeat</blockquote></li><ul> <li>(1) Autosomal dominant</li><li>(2) Most common adult muscular dystrophy</li><li>(3) Trinucleotide repeat (CTG) disorder (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><li>(4) Selective atrophy of type I fibers</li> </ul><li>Clinical findings (<span>[[Fig. 23-21|Figure 23-21]]</span>)
<blockquote style="color: blue; ">Myotonia: inability to relax muscles</blockquote></li><ul> <li>(1) Facial muscle weakness</li><ul> <li>Sagging face; problem in closing the mouth</li> </ul><li>(2) Percussion and grip myotonia</li><ul> <li>Inability to relax muscles (sustained grip)</li> </ul><li>(3) Frontal balding; cataracts
<blockquote style="color: blue; ">MD: sagging face; frontal balding; cataracts; testicular atrophy; cardiac involvement</blockquote></li><li>(4) Testicular atrophy; glucose intolerance</li><li>(5) Cardiac involvement (conduction defects)</li> </ul><li>Increased serum CK</li><li>No specific treatment</li> </ol><li>Myasthenia gravis (MG)</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Afflicts men in sixth and seventh decades of life</li><li>(2) Afflicts women in second and third decades of life</li> </ul><li>Pathogenesis</li><ul> <li>(1) Autonomic disorder of postsynaptic neuromuscular transmission</li><li>(2) Autoantibody against acetylcholine receptors
<blockquote style="color: blue; ">MG: autoantibodies against ACh receptors; synthesized in thymus</blockquote></li><ul> <li>(a) Type II hypersensitivity reaction</li><li>(b) Antibodies inhibit or destroy the receptors.</li><li>(c) Decrease in functional ACh receptors</li> </ul><li>(3) Antibody is synthesized in the thymus.</li><ul> <li>Thymic hyperplasia with germinal follicles (85% of cases)</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Fluctuating muscle weakness</li><ul> <li>Worsened with exercise, improved with rest</li> </ul><li>(2) Ptosis is the most common initial finding (<span>[[Fig. 23-22|Figure 23-22]]</span>).
<blockquote style="color: blue; ">MG: ptosis, diplopia common initial finding</blockquote></li><ul> <li>Diplopia is due to eye muscle weakness.</li> </ul><li>(3) Weakness in proximal muscles, diaphragm, neck extension (85%)</li><li>(4) Dysphagia for solids and liquids
<blockquote style="color: blue; ">MG: oropharyngeal dysphagia for solids/liquids</blockquote></li><ul> <li>Occurs in the upper esophagus (striated muscle)</li> </ul><li>(5) Normal reflexes, sensation, and coordination</li><li>(6) Increased risk for developing a thymoma (15%)</li> </ul><li>Diagnosis</li><ul> <li>(1) Tensilon (edrophonium) test
<blockquote style="color: blue; ">Tensilon: inhibits acetylcholinesterase</blockquote></li><ul> <li>(a) Inhibits acetylcholinesterase</li><li>(b) Increase in acetylcholine reverses muscle weakness</li> </ul><li>(2) Single-fiber electromyography (abnormal in 95% of MG)</li> </ul><li>Treatment</li><ul> <li>(1) Avoid certain medications</li><ul> <li>β-Blockers; aminoglycosides; quinolone antibiotics; class 1 antiarrhythmics</li> </ul><li>(2) Pyridostigmine (acetylcholinesterase inhibitor)</li><li>(3) Immunosuppressive drugs</li><ul> <li>Corticosteroids; azathioprine; mycophenolate mofetil; cyclosporine</li> </ul><li>(4) Plasmapheresis (short-term treatment; removes antibodies)</li><li>(5) Thymectomy (removes site for antibody production)</li> </ul> </ol> </ol>
</div></html>
![[23.III.A.Muscle fibers]]
<<tiddler [[23.III.A.Muscle fibers]]>>
![[23.III.B.Muscle disorders]]
<<tiddler [[23.III.B.Muscle disorders]]>>
<html><a name="HC023030"></a> <br><a name="P023048"></a><div class="PA" style="color: black; "><ol type="1"> <li>Non-neoplastic, proliferative connective tissue disorder</li><li>Fibrous tissue infiltrates tissue (usually muscle).</li><li>Dupuytren's contracture (<span>[[Fig. 23-23|Figure 23-23]]</span>)
<blockquote style="color: blue; ">Dupuytren's contracture: fibromatosis palmar fascia</blockquote></li><ol type="a"> <li>Fibromatosis involving palmar fascia</li><li>Causes contraction of single or multiple fingers</li><li>Associated with alcoholism</li> </ol><li>Desmoid tumor</li><ol type="a"> <li>Fibromatosis of the anterior abdominal wall in women
<blockquote style="color: blue; ">Liposarcoma: most common adult sarcoma</blockquote></li><li>Associated with previous trauma
<blockquote style="color: blue; ">Unhappy triad: damage to medial meniscus, medial collateral ligament, anterior cruciate ligament</blockquote></li><li>Associated with Gardner's polyposis syndrome</li> </ol> </ol>
</div></html>
<html><a name="HC023031"></a><span>[[21-4|Figure 21-4]]</span> <br><span>[[Figs. 8-1B|Figure 8-1]]</span> <br><span>[[Table 23-2|Table 23-2. SOFT TISSUE TUMORS]]</span> <br> <br> </html>
![[23.IV.A.Fibromatosis]]
<<tiddler [[23.IV.A.Fibromatosis]]>>
![[23.IV.B.Selected soft tissue tumors (Table 23-2; see also Figs. 8-1B and 21-4)]]
<<tiddler [[23.IV.B.Selected soft tissue tumors (Table 23-2; see also Figs. 8-1B and 21-4)]]>>
<html><a name="HC023032"></a><span>[[Fig. 23-24A to D|Figure 23-24]]</span> <br><span>[[Table 23-3|Table 23-3. SELECTED ORTHOPEDIC DISORDERS]]</span> <br> <br></html>
![[23.V.A.Selected Orthopedic Disorders (Table 23-3 and Fig. 23-24A to D)]]
<<tiddler [[23.V.A.Selected Orthopedic Disorders (Table 23-3 and Fig. 23-24A to D)]]>>
<html><a name="HC024002"></a> <br><a name="P024001"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidermis</li><ol type="a"> <li>Stratum basalis
<blockquote style="color: blue; ">Stratum basalis: stem cells for division</blockquote></li><ul> <li>(1) Actively dividing stem cells along the basement membrane</li><li>(2) Mitoses should be limited to this area.</li> </ul><li>Stratum spinosum</li><ul> <li>Contains prominent desmosome attachments</li> </ul><li>Stratum granulosum</li><ul> <li>Granular layer with keratohyaline granules</li> </ul><li>Stratum corneum</li><ul> <li>(1) Anucleate cells with keratin
<blockquote style="color: blue; ">Stratum corneum: site for superficial dermatophyte infections</blockquote></li><li>(2) Site for superficial dermatophyte infections</li> </ul> </ol><li>Dermis</li><ol type="a"> <li>Papillary</li><ul> <li>Loose connective tissue beneath the epidermis</li> </ul><li>Reticular</li><ul> <li>Dense dermal collagen</li> </ul> </ol><li>Melanocytes
<blockquote style="color: blue; ">Melanocytes: neural crest origin</blockquote></li><ol type="a"> <li>Derived from neural crest cells</li><li>Located in stratum basalis</li><ul> <li>Dendritic processes extend between keratinocytes.</li> </ul><li>Melanin is synthesized in membrane-bound melanosomes.
<blockquote style="color: blue; ">Melanin: synthesized from tyrosine; synthesized in melanosomes</blockquote></li><ul> <li>(1) Tyrosinase converts tyrosine to 3,4-dihydroxyphenylalanine (DOPA).</li><li>(2) DOPA is converted to melanin.</li><li>(3) Melanosomes are transferred by dendritic processes to keratinocytes.
<blockquote style="color: blue; ">Melanosomes: transferred by dendritic processes to keratinocytes</blockquote></li> </ul><li>Skin color</li><ul> <li>(1) Number of melanocytes is essentially the <i>same</i> in all races.</li><li>(2) Melanin is degraded more rapidly in whites than in blacks.</li><li>(3) In whites, melanosomes are concentrated in the basal layer.</li><li>(4) In blacks, melanosomes are present throughout all layers.
<blockquote style="color: blue; ">Blacks: melanosomes in all layers; melanocytes larger/more dendritic processes</blockquote></li><ul> <li>Melanocytes are larger and have more dendritic processes.</li> </ul> </ul><li>Sunlight and adrenocorticotropic hormone stimulate melanin synthesis.</li> </ol> </ol>
</div></html>
<html><a name="HC024003"></a><span>[[Table 24-1|Table 24-1. COMMON TERMS IN DERMATOLOGY]]</span> <br> <br> </html>
![[24.I.A.Normal skin histology]]
<<tiddler [[24.I.A.Normal skin histology]]>>
![[24.I.B.Common terms used in dermatology (Table 24-1)]]
<<tiddler [[24.I.B.Common terms used in dermatology (Table 24-1)]]>>
<html><a name="HC024005"></a> <br><a name="P024002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Caused by human papillomavirus (HPV; DNA virus)
<blockquote style="color: blue; ">Common wart: HPV</blockquote></li><li>Common sites are the fingers and soles.</li><li>Verrucous papular lesions covered by scales (<span>[[Fig. 24-1A|Figure 24-1]]</span>)</li><li>Treatment</li><ol type="a"> <li>Physical therapy-e.g., cryotherapy with liquid nitrogen</li><li>Chemotherapy-e.g., salicylic acid, trichloroacetic acid</li><li>Biologic therapeutic agent-imiquimod (induces cytokines)</li> </ol> </ol>
</div></html>
<html><a name="HC024006"></a> <br><a name="P024003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Caused by a poxvirus (DNA virus)
<blockquote style="color: blue; ">Molluscum contagiosum: poxvirus; umbilicated lesions with viral particles</blockquote></li><li>Bowl-shaped lesions with central depression filled with keratin (<span>[[Fig. 24-1B|Figure 24-1]]</span>)</li><ul> <li>Depression contains viral particles called molluscum bodies.</li> </ul><li>Transmission</li><ol type="a"> <li>Can be sexually transmitted in adults (common in AIDS)
<blockquote style="color: blue; ">Molluscum contagiosum: common in AIDS</blockquote></li><li>Self-inoculation by scratching the infective viral particles out of the crater</li> </ol><li>Treatment</li><ol type="a"> <li>Spontaneous remission occurs in 6 to 9 months if immunocompetent.</li><ul> <li>Cell-mediated immunity</li> </ul><li>Cryotherapy
<blockquote style="color: blue; ">Rubeola: regular measles</blockquote></li> </ol> </ol>
</div></html>
<html><a name="HC024007"></a> <br><a name="P024004"></a><div class="PA" style="color: black; "><ol type="1"> <li>RNA paramyxovirus</li><li>Vaccination has reduced the incidence of rubeola.
<blockquote style="color: blue; ">Prodrome 3 Cs: <i>c</i>ough, <i>c</i>oryza, <i>c</i>onjunctivitis</blockquote></li><li>Prodrome</li><ul> <li>Fever, cough, coryza (runny nose), conjunctivitis</li> </ul><li>Koplik spots develop on the buccal mucosa.</li><ul> <li>Koplik spots are white spots overlying an erythematous base (<span>[[Fig. 24-1C|Figure 24-1]]</span>).
<blockquote style="color: blue; ">Rubeola: rash after Koplik spots disappear</blockquote></li> </ul><li>Maculopapular rash develops <i>after</i> Koplik spots disappear (<span>[[Fig. 24-1D|Figure 24-1]]</span>).</li><ol type="a"> <li>Cytotoxic T cell damage of endothelial cells containing the virus</li><li>Typically begins on the head and then to the trunk and extremities</li><li>Tends to become confluent on face and trunk but discrete on extremities</li> </ol><li>Complications
<blockquote style="color: blue; ">Rubeola: giant cell pneumonia; acute appendicitis (children); otitis media</blockquote></li><ol type="a"> <li>Giant cell pneumonia</li><ul> <li>Warthin-Finkeldey multinucleated giant cells</li> </ul><li>Acute appendicitis in children</li><li>Otitis media</li><li>Encephalitis</li><ul> <li>Before immunization, encephalitis was a common cause of death in measles.</li> </ul><li><i>Not</i> teratogenic</li> </ol><li>Prevented through vaccinations</li> </ol>
</div></html>
<html><a name="HC024008"></a> <br><a name="P024005"></a><div class="PA" style="color: black; "><ol type="1"> <li>RNA togavirus</li><ul> <li>Produces "3-day measles"</li> </ul><li>Vaccination has reduced the incidence of rubella.</li><li>Forchheimer's spots (see <span>[[Fig. 21-1E|Figure 21-1]]</span>)</li><ol type="a"> <li>Dusky red spots that develop on posterior soft/hard palate</li><li>Develop at beginning of the rash.</li> </ol><li>Maculopapular rash lasts 3 days (see <span>[[Fig. 21-1F|Figure 21-1]]</span>).
<blockquote style="color: blue; ">Rubella: maculopapular rash with discrete lesion; not confluent; fades in 3 days</blockquote></li><ol type="a"> <li>Pinkish, red maculopapular eruption</li><li>Begins first at hairline and rapidly spreads cephalocaudally</li><li>Unlike rubeola, the macules and papules are discrete and do <i>not</i> become confluent.</li><li>Fades in 3 days</li> </ol><li>Painful postauricular lymphadenopathy (characteristic)
<blockquote style="color: blue; ">Rubella: painful postauricular lymphadenopathy</blockquote></li><li>Polyarthritis is common in adults.</li><li>Infection during first trimester may produce congenital anomalies (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>).</li><li>Prevent through vaccination
<blockquote style="color: blue; ">Rubella: teratogenic</blockquote></li> </ol>
</div></html>
<html><a name="HC024009"></a> <br><a name="PB024001"></a><div class="BB" style="color: rgb(47, 79, 79); ">Other disorders caused by parvovirus B19 include pure red blood cell aplasia and aplastic anemia in chronic hemolytic diseases (e.g., hereditary spherocytosis) and chronic arthritis. Pregnant mothers exposed to a child with the infection may abort the fetus.</div><a name="P024006"></a><div class="PA" style="color: black; "><ol type="1"> <li>Caused by parvovirus B19 (DNA virus)</li><li>Most often occurs in school age children</li><ul> <li>Often occurs in epidemics</li> </ul><li>Confluent net-like erythema type of rash
<blockquote style="color: blue; ">Erythema infectiosum: parvovirus; slapped face appearance</blockquote></li><ol type="a"> <li>Begins on the cheeks ("slapped face" appearance; <span>[[Fig. 24-1G|Figure 24-1]]</span>)</li><li>Extends to the trunk and proximal extremities</li> </ol><li>Polyarthritis is common in adults.
<blockquote style="color: blue; ">Polyarthritis in adults: rubella and parvovirus</blockquote></li> </ol>
</div></html>
<html><a name="HC024010"></a> <br><a name="P024007"></a><div class="PA" style="color: black; "><ol type="1"> <li>Caused by human herpesvirus 6 (DNA virus)
<blockquote style="color: blue; ">Roseola: HHV-6; most common viral exanthem children < 2 years old</blockquote></li><li>Most common viral exanthem in children < 2 years old</li><li>Erythematous macules develop on soft palate 48 hours <i>before</i> rash.</li><li>Maculopapular rash occurs abruptly after 3 to 7 days of high fever (<span>[[Fig. 24-1H|Figure 24-1]]</span>).
<blockquote style="color: blue; ">Roseola: common cause of febrile convulsions</blockquote></li><li>High fever may precipitate a febrile convulsion.</li> </ol>
</div></html>
<html><a name="HC024011"></a> <br><a name="P024008"></a><div class="PA" style="color: black; "><ol type="1"> <li>DNA herpesvirus</li><ul> <li>Remains latent in cranial and thoracic sensory ganglia</li> </ul><li>Varicella (chickenpox)</li><ol type="a"> <li>Predominantly a childhood disease
<blockquote style="color: blue; ">Varicella: predominantly a childhood disease</blockquote></li><ul> <li>(1) Approximately 90% of cases occur in those <10 years of age.</li><li>(2) Peaks in spring months</li> </ul><li>Incubation 2 to 3 weeks</li><li>Patient is infectious 1 week <i>before</i> the rash appears.</li><ul> <li>Infectious an additional 4 to 5 days until vesicles become crusted
<blockquote style="color: blue; ">Infectious: week before rash; week after rash until vesicles become crusted</blockquote></li> </ul><li>Pruritic rash progresses from macules, to vesicles, to pustules (<span>[[Fig. 24-1I|Figure 24-1]]</span>).</li><ul> <li>(1) All stages of development are simultaneously present.</li><li>(2) Lesions are most prominent on the trunk.</li><ul> <li>(a) Also involves extremities (including palms and soles), mucous membranes in mouth, conjunctiva
<blockquote style="color: blue; ">Varicella: macules, vesicles, pustules</blockquote></li><li>(b) Vesicles are often umbilicated (depressed center) and hemorrhagic.</li> </ul> </ul><li>Positive Tzanck test similar to herpes simplex virus (refer to <span macro="tag [[21 Female Reproductive Disorders and Breast Disorders]] [[Chapter 21]]"></span>)</li><li>Complications</li><ul> <li>(1) Association with Reye syndrome
<blockquote style="color: blue; ">Complications: children-Reye syndrome, cerebellitis; adult-pneumonia, encephalitis, hepatitis</blockquote></li><li>(2) Pneumonia, self-limited cerebellitis</li><li>(3) In adults-hepatitis, pneumonia, encephalitis</li><ul> <li>Treated with acyclovir</li> </ul> </ul><li>Treatment</li><ul> <li>(1) Prevention with immunization</li><li>(2) Antihistamine; oatmeal bath; calamine lotion</li> </ul> </ol><li>Herpes zoster (shingles)</li><ol type="a"> <li>Occurs in 10% to 20% of people in their lifetime.</li><li>Incidence increases with age.
<blockquote style="color: blue; ">Herpes zoster: incidence increases with age; cancer; immunocompromised state</blockquote></li><li>Incidence increased in patients with cancer and AIDS</li><li>Prodrome of radicular pain and itching <i>before</i> rash occurs</li><li>Eruption characterized by groups of vesicles on an erythematous base</li><ul> <li>(1) Rash follows sensory dermatomes in the distribution of cranial nerves or spinal nerves (<span>[[Fig. 24-1J|Figure 24-1]]</span>).
<blockquote style="color: blue; ">Herpes zoster: painful vesicles/pustules follow sensory dermatomes</blockquote></li><li>(2) Like varicella, pustules form that rupture, causing crusting and weeping.</li> </ul><li>Treatment</li><ul> <li>(1) Prevention with previous immunization for varicella</li><li>(2) Prevention with zoster vaccine</li><ul> <li>Greater than 50% reduction in infection</li> </ul><li>(3) Analgesics commensurate with amount of pain</li><li>(4) Immunocompromised patients are often treated with acyclovir, valacyclovir, or famiciclovir.</li><ul> <li>Best started <i>before</i> the rash has erupted</li> </ul> </ul> </ol> </ol>
</div></html>
![[24.II.A.Common warts]]
<<tiddler [[24.II.A.Common warts]]>>
![[24.II.B.Molluscum contagiosum]]
<<tiddler [[24.II.B.Molluscum contagiosum]]>>
![[24.II.C.Rubeola (measles)]]
<<tiddler [[24.II.C.Rubeola (measles)]]>>
![[24.II.D.Rubella (German measles)]]
<<tiddler [[24.II.D.Rubella (German measles)]]>>
![[24.II.E.Erythema infectiosum (fifth disease)]]
<<tiddler [[24.II.E.Erythema infectiosum (fifth disease)]]>>
![[24.II.F.Roseola infantum]]
<<tiddler [[24.II.F.Roseola infantum]]>>
![[24.II.G.Disorders caused by varicella-zoster virus]]
<<tiddler [[24.II.G.Disorders caused by varicella-zoster virus]]>>
<html><a name="HC024013"></a> <br><a name="P024010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Gram-positive coccus (<span>[[Fig. 24-2A|Figure 24-2]]</span>)
<blockquote style="color: blue; "><i>S. aureus</i>: gram-positive coccus in clumps</blockquote></li><li>Toxic shock syndrome</li><ol type="a"> <li>Production of toxic shock syndrome toxin (TSST)
<blockquote style="color: blue; ">TSST: produces desquamating sunburn-like rash</blockquote></li><ul> <li>Superantigen that stimulates release of cytokines</li> </ul><li>Usually occurs in tampon-using menstruating women</li><li>Clinical findings</li><ul> <li>(1) Fever, hypotension</li><li>(2) Desquamating, sunburn-like rash</li> </ul> </ol><li>Other infections</li><ol type="a"> <li>Skin abscess (see <span>[[Fig. 2-6|Figure 2-6]]</span>)</li><ul> <li>Treatment: trimethoprim-sulfamethoxazole (TMP-SMX; community acquired)</li> </ul><li>Hidradenitis suppurativa</li><ul> <li>(1) Chronic condition characterized by:</li><ul> <li>(a) Swollen, painful, inflamed apocrine glands usually in the axillae and groin</li><li>(b) Infection can also involve adjacent subcutaneous tissue and fascia.</li><li>(c) Hallmark is the presence of sinus tracts.</li> </ul><li>(2) Must aspirate and culture pus</li><li>(3) Difficult to treat; may require surgery
<blockquote style="color: blue; "><i>S. aureus</i> infections: abscess, postsurgical wound infection; hidradenitis; impetigo</blockquote></li> </ul><li>Postsurgical wound infection (most common pathogen)</li><ul> <li>(1) If not septic, treat with TMP-SMX double strength.</li><li>(2) If septic, treat with IV vancomycin.</li> </ul><li>Impetigo</li><ul> <li>(1) Most often caused by <i>Staphylococcus aureus</i></li><ul> <li><i>Streptococcus pyogenes</i> second most common cause</li> </ul><li>(2) Rash usually begins on the face (<span>[[Fig. 24-2B|Figure 24-2]]</span>).</li><ul> <li>Vesicles and pustules rupture to form honey-colored, crusted lesions.</li> </ul><li>(3) Bullae commonly occur.</li><li>(4) Treatment</li><ul> <li>Mupirocin ointment + dicloxacillin (or oxacillin, amoxicillin-clavulanate, azithromycin)</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC024014"></a> <br><a name="P024011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Gram-positive coccus (<span>[[Fig. 24-2C|Figure 24-2]]</span>)
<blockquote style="color: blue; "><i>S. pyogenes</i>: gram-positive coccus in chains</blockquote></li><li>Scarlet fever</li><ol type="a"> <li>Particular strains of <i>S. pyogenes</i> produce an erythrogenic toxin.</li><li>Patients are febrile and have a sore throat due to streptococcal pharyngitis.</li><li>An erythematous rash develops that involves the skin and tongue.
<blockquote style="color: blue; ">Scarlet fever: erythrogenic toxin; erythematous sandpapery rash that desquamates</blockquote></li><ul> <li>(1) It initially occurs on the face and neck before spreading to other parts of the body.</li><li>(2) It spares the mouth producing conspicuous circumoral pallor.</li><li>(3) It has a sandpapery feeling.</li><li>(4) The tongue is covered by a white exudate studded with prominent red papillae.</li><li>(5) The rash begins to fade after 6 days and desquamation (peeling) begins, which may last up to 10 days.</li><li>(6) The white exudate on the tongue disappears; tongue is beefy red, hence the term "strawberry tongue."
<blockquote style="color: blue; ">Scarlet fever: ↑ risk poststreptococcal glomerulonephritis, rheumatic fever</blockquote></li> </ul><li>Increased risk for developing poststreptococcal glomerulonephritis (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>) and rheumatic fever (refer to <span macro="tag [[10 Heart Disorders]] [[Chapter 10]]"></span>)</li><li>Treatment is penicillin V.</li> </ol><li>Erysipelas</li><ol type="a"> <li>Type of cellulitis</li><ul> <li>(1) Border is raised and surface appears like an orange peel (see <span>[[Fig. 2-1|Figure 2-1]]</span>).</li><li>(2) Skin surface is hot and bright red (rubor of acute inflammation).
<blockquote style="color: blue; ">Erysipelas: cellulitis with raised borders</blockquote></li> </ul><li>Commonly occurs on the face and lower extremities</li><li>Patient feels ill and is febrile.</li><li>Treatment is IV penicillin G if on extremities; vancomycin if on the face</li> </ol> </ol>
</div></html>
<html><a name="HC024015"></a> <br><a name="P024012"></a><div class="PA" style="color: black; "><ol type="1"> <li>Caused by <i>Mycobacterium leprae</i></li><ul> <li>Grows in footpads of mice and armadillos; <i>cannot</i> be cultured</li> </ul><li>Tuberculoid type
<blockquote style="color: blue; ">Tuberculoid: granuloma; intact cellular immunity; + lepromin skin test</blockquote></li><ol type="a"> <li>Granulomas present</li><ul> <li>Very few acid-fast bacteria are present in the granulomas.</li> </ul><li>Positive lepromin skin test</li><ul> <li>Indicates intact cellular immunity</li> </ul><li>Localized skin lesions with nerve involvement</li><ul> <li>(1) Autoamputation of digits
<blockquote style="color: blue; ">Tuberculoid: digital autoamputation; hypopigmented skin</blockquote></li><li>(2) Anesthetic macules with hypopigmentation (<span>[[Fig. 24-2D|Figure 24-2]]</span>)</li> </ul><li>Treatment</li><ul> <li>Dapsone + rifampin</li> </ul> </ol><li>Lepromatous type
<blockquote style="color: blue; ">Lepromatous: organisms present; impaired cellular immunity; - lepromin skin test</blockquote></li><ol type="a"> <li>Absence of granulomas</li><ul> <li>(1) Numerous bacteria are present in foamy macrophages.</li><li>(2) Macrophages are located under a subepidermal zone free of organisms.</li><ul> <li>Called the Grenz zone</li> </ul> </ul><li>Negative lepromin skin test</li><ul> <li>Indicates a lack of cellular immunity
<blockquote style="color: blue; ">Lepromatous: leonine facies</blockquote></li> </ul><li>Nodular lesions produce the classic leonine facies (<span>[[Fig. 24-2E|Figure 24-2]]</span>).</li><li>Treatment</li><ul> <li>Dapsone + rifampin + clofazimine</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC024016"></a> <br><a name="P024013"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Acne vulgaris: chronic inflammation of pilosebaceous unit</blockquote>
<ol type="1"> <li>Chronic inflammation of the pilosebaceous unit</li><li>Most common disease seen by dermatologists</li><li>Begins at an early age (9-11 years old)</li><li>Increases in severity in teenage years</li><li>Clinical lesions</li><ul> <li>Inflammatory papules, pustules, nodules, cysts</li> </ul><li>Noninflamed comedones
<blockquote style="color: blue; ">Comedones: open ("blackhead"), closed ("whitehead")</blockquote></li><ol type="a"> <li>Plugging of the outlet of a hair follicle by keratin debris</li><li>Open comedone is called a "blackhead."</li><li>Closed comedone is called a "whitehead."</li> </ol><li>Inflammatory type</li><ol type="a"> <li>Abnormal keratinization of the follicular epithelium
<blockquote style="color: blue; ">Acne vulgaris: androgen receptors located on sebaceous glands</blockquote></li><li>Increased sebum production (androgen-dependent)</li><li>Bacterial lipase <i>(Propionibacterium acnes)</i> produces irritating fatty acids.</li><ul> <li>Produces the inflammatory reaction (<span>[[Fig. 24-2F|Figure 24-2]]</span>)
<blockquote style="color: blue; ">Acne vulgaris: <i>Propionibacterium acnes</i> produces lipase</blockquote></li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Topical agents-e.g., topical retinoid + benzoyl peroxide</li><li>Systemic antibiotics-e.g., tetracycline (first choice); erythromycin</li><li>Systemic retinoids-isotretinoin (decreases follicular keratinization, sebum production, bacterial count)</li><li>Hormonal therapy-oral contraceptives (women; reduce free testosterone levels); antiandrogens (spironolactone)</li> </ol> </ol>
</div></html>
![[24.III.A.Staphylococcus aureus skin infections]]
<<tiddler [[24.III.A.Staphylococcus aureus skin infections]]>>
![[24.III.B.Streptococcus pyogenes skin infections]]
<<tiddler [[24.III.B.Streptococcus pyogenes skin infections]]>>
![[24.III.C.Leprosy]]
<<tiddler [[24.III.C.Leprosy]]>>
![[24.III.D.Acne vulgaris]]
<<tiddler [[24.III.D.Acne vulgaris]]>>
<html><a name="HC024018"></a> <br><a name="PB024002"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Wood's lamp and potassium hydroxide (KOH)-treated skin scrapings</b> from lesions are commonly used for diagnosis of the dermatophytoses. Wood's lamp (ultraviolet A light) detects fluorescent metabolites produced by organisms (e.g., fungi, some bacteria). KOH preparations identify yeasts and hyphae in the stratum corneum or hair shafts (<span>[[Fig. 24-3A|Figure 24-3]]</span>).
<blockquote style="color: blue; ">Wood's lamp: detects fluorescent fungal metabolites</blockquote></div><a name="P024015"></a><div class="PA" style="color: black; "><ol type="1"> <li>Fungi confined to the stratum corneum or its adnexal structures
<blockquote style="color: blue; ">Superficial dermatophytes: live in stratum corneum</blockquote></li><ol type="a"> <li>Incidence increases in warm, humid climates.</li><li>Most infections present with a scaling rash.</li><li>Tinea actually means "worm" in Latin, but is applied to describe superficial fungal infections.</li><ul> <li>(1) Tinea is followed by a word that qualifies its location (e.g., capitis, pedis, corporis)</li><li>(2) Most common infections in decreasing order-tinea pedis (foot), tinea unguim (nail), tinea versicolor (describes color variation rather than location), tinea cruris (groin)</li> </ul> </ol><li>Tinea capitis</li><ol type="a"> <li>Superficial fungal infection of scalp</li><li>Pathogens</li><ul> <li>(1) Most often caused by <i>Trichophyton tonsurans</i>
<blockquote style="color: blue; "><i>T. tonsurans:</i> most common cause in blacks; - Wood's lamp</blockquote></li><ul> <li>(a) Infects the inner hair shaft</li><li>(b) Negative Wood's lamp</li><li>(c) Predominant type present in blacks</li> </ul><li>(2) <i>Microsporum canis</i> and <i>Microsporum audouinii</i>
<blockquote style="color: blue; "><i>M. canis/audouinii:</i> most common cause in whites; + Wood's lamp</blockquote></li><ul> <li>(a) Former type is associated with exposure to dogs.</li><li>(b) Both infect the outer hair shaft.</li><li>(c) Positive Wood's lamp</li><li>(d) Predominant pathogens in whites
<blockquote style="color: blue; ">Tinea capitis: oral terbinafine; topical imidazoles do not work</blockquote></li> </ul> </ul><li>Circular or ring-shaped patches of hair loss (alopecia)</li><ul> <li>Black dot is present where hair breaks off (<span>[[Fig. 24-3B|Figure 24-3]]</span>).</li> </ul><li>Treatment is oral terbinafine.
<blockquote style="color: blue; "><i>T. rubrum:</i> most common cause of all other tineas (except versicolor)</blockquote></li> </ol><li>Other infections are most often caused by <i>Trichophyton rubrum</i>.</li><ol type="a"> <li>Tinea corporis (body surface) (<span>[[Fig. 24-3C|Figure 24-3]]</span>)</li><ul> <li>(1) Sometimes called "ringworm"</li><li>(2) May have history of exposure to cat or dog</li><li>(3) One or more lesions may be present.
<blockquote style="color: blue; ">Tinea corporis: annular; outer border raised/scaly; central clearing</blockquote></li><li>(4) Typically are annular with an elevated red, scaly border</li><ul> <li>Tendency for central clearing</li> </ul><li>(5) Treatment uses topical agents (e.g., miconazole, clotrimazole).</li><ul> <li>Can use oral terbinafine as an alternative</li> </ul> </ul><li>Tinea pedis ("athlete's foot")
<blockquote style="color: blue; ">Tinea pedis: most common tinea infection; sweating important cause</blockquote></li><ul> <li>(1) Most common site for infection</li><li>(2) Most common in patient with sweaty feet</li><li>(3) Macerated scaling rash between the toes</li><li>(4) Elderly people have diffuse plantar scaling</li><ul> <li>"Moccasin" appearance</li> </ul><li>(5) Treatment is with topical agents (e.g., miconazole, clotrimazole).</li><ul> <li>Can use oral terbinafine as an alternative</li> </ul> </ul><li>Tinea cruris (groin; "jock itch") (<span>[[Fig. 24-3D|Figure 24-3]]</span>)
<blockquote style="color: blue; ">Tinea cruris: sweat is important in pathogenesis</blockquote></li><ul> <li>(1) Frequently also have tinea pedis</li><li>(2) Both are areas for excessive sweating.</li><li>(3) Rash is <i>not</i> annular but has elevated, scaly borders.</li><li>(4) Scrotum is involved.</li><li>(5) Treatment uses topical agents (e.g., miconazole, clotrimazole).</li><ul> <li>Can use oral terbinafine as an alternative</li> </ul> </ul><li>Tinea unguium (nail; onychomycosis)</li><ul> <li>(1) Second most common superficial dermatophyte infection
<blockquote style="color: blue; ">Onychomycosis: raised, discolored nail; nail plate white, thick, crumbly</blockquote></li><li>(2) <i>T. rubrum</i> (most common) and <i>T. mentagrophytes</i> most common dermatophytes</li><li>(3) Nail is raised and nail plate is white, thick, and crumbly.</li><li>(4) Nail is frequently discolored.</li><li>(5) Treatment
<blockquote style="color: blue; ">Rx onychomycosis: oral terbinafine</blockquote></li><ul> <li>(a) Topical agents do not work.</li><li>(b) Oral therapy with terbinafine (best) or itraconazole</li> </ul> </ul> </ol><li>Tinea versicolor</li><ol type="a"> <li>Tinea with alteration with skin pigmentation
<blockquote style="color: blue; ">Tinea versicolor: alteration in skin pigmentation; hypopigmentation or hyperpigmentation</blockquote></li><ul> <li>(1) Hypopigmented type is due to decrease in melanin synthesis.</li><li>(2) Hyperpigmented type is due to an enlargement of melanosomes.</li> </ul><li>Wood's lamp accentuates the color variation in skin.</li><li>Caused by <i>Malassezia furfur</i></li><ul> <li>(1) In hypopigmented type, fungus-derived acids inhibit tyrosinase in melanocytes from synthesizing melanin.</li><li>(2) In hyperpigmented type, fungus induces enlargement of melanosomes in melanocytes along the basal cell layer.
<blockquote style="color: blue; "><i>M. furfur:</i> tinea versicolor; "spaghetti" and "meatballs" KOH appearance</blockquote></li> </ul><li>Affected skin does <i>not</i> tan ("white spots"); normal skin does (<span>[[Fig. 24-3E|Figure 24-3]]</span>).</li><ul> <li>Lesions become hyperpigmented and scaly in winter months.</li> </ul><li>KOH findings (<span>[[Fig. 24-3F|Figure 24-3]]</span>)</li><ul> <li>(1) Hypopigmented/hyperpigmented areas have the organism.</li><li>(2) Short hyphae have the appearance of "spaghetti."</li><li>(3) Yeasts have the appearance of "meatballs."</li> </ul><li>Treatment</li><ul> <li>(1) Topical selenium sulfide</li><li>(2) Oral ketoconazole (best treatment)</li> </ul> </ol><li>Infections caused by <i>Candida albicans</i></li><ol type="a"> <li>Intertrigo</li><ul> <li>(1) Erythematous rash in body folds</li><ul> <li>KOH shows pseudohyphae and yeast (see <span>[[Fig. 21-1A|Figure 21-1]]</span>).</li> </ul><li>(2) Examples-rash under pendulous breasts, diaper rash
<blockquote style="color: blue; "><i>Candida</i> skin infections: intertrigo; diaper rash; onychomycosis</blockquote></li><li>(3) Treatment is topical agents (e.g., miconazole, clotrimazole)</li> </ul><li>Onychomycosis</li><ul> <li>(1) Nail infection</li><li>(2) Treatment</li><ul> <li>(a) Topical-amphotericin B, clotrimazole, econazole</li><li>(b) Oral ketoconazole</li> </ul> </ul> </ol><li>Seborrheic dermatitis (dandruff)</li><ol type="a"> <li>Affects 3% to 5% of population</li><li>Caused by <i>M. furfur</i></li><li>Common associations
<blockquote style="color: blue; ">Seborrheic dermatitis: dandruff; <i>M. furfur</i></blockquote></li><ul> <li>(1) Parkinson's disease</li><li>(2) AIDS and AIDS-related complex</li> </ul><li>Scaly, yellowish, greasy dermatitis (<span>[[Fig. 24-3G|Figure 24-3]]</span>)</li><li>Locations</li><ul> <li>(1) Scalp (dandruff), eyebrows, and nasal creases
<blockquote style="color: blue; ">Seborrheic dermatitis: called cradle cap in newborns</blockquote></li><li>(2) Called cradle cap in newborns</li> </ul><li>Treatment</li><ul> <li>Shampoo-selenium sulfide, zinc pyrithione; may need higher prescription doses of these over-the-counter shampoos</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC024019"></a> <br><a name="P024016"></a><div class="PA" style="color: black; "><ol type="1"> <li>Caused by <i>Sporothrix schenckii</i>
<blockquote style="color: blue; ">Sporotrichosis: subcutaneous mycosis; <i>Sporothrix schenckii</i></blockquote></li><ol type="a"> <li>Subcutaneous mycotic infection</li><li>Dimorphic fungus</li><ul> <li>Mold in soil, yeast in tissue
<blockquote style="color: blue; ">Sporotrichosis: traumatic implantation</blockquote></li> </ul> </ol><li>Traumatic implantation of fungus</li><ol type="a"> <li>Rose gardening</li><li>Sphagnum peat moss for packing material</li><li>Splinters from carpentry work</li><li>Landscapers; berry-pickers</li> </ol><li>Lymphocutaneous disease
<blockquote style="color: blue; ">Sporotrichosis: chain of suppurating lymphocutaneous nodules</blockquote></li><ul> <li>Chain of suppurating lymphocutaneous nodules (<span>[[Fig. 24-3H|Figure 24-3]]</span>)</li> </ul><li>Treatment</li><ol type="a"> <li>Oral itraconazole</li><li>Saturated solution of potassium iodide (SSKI)</li><ul> <li>Poorly tolerated; not the treatment of choice</li> </ul> </ol> </ol>
</div></html>
![[24.IV.A.Superficial mycoses (dermatophytoses)]]
<<tiddler [[24.IV.A.Superficial mycoses (dermatophytoses)]]>>
![[24.IV.B.Sporotrichosis]]
<<tiddler [[24.IV.B.Sporotrichosis]]>>
<html><a name="HC024042"></a> <br><a name="P024039"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Ichthyosis vulgaris: most common inherited skin disorder; ↑ stratum corneum</blockquote>
<ol type="1"> <li>Autosomal dominant</li><ul> <li>Most common inherited skin disorder</li> </ul><li>Defect in keratinization</li><ol type="a"> <li>Causes increased thickness of the stratum corneum</li><li>Absent stratum granulosum</li> </ol><li>Hyperkeratotic, dry skin</li><ul> <li>Involves palms, soles, and extensor areas</li> </ul> </ol>
</div></html>
<html><a name="HC024043"></a> <br><a name="P024040"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common cause of dry skin and pruritus in the elderly
<blockquote style="color: blue; ">Xerosis: most common cause of dried skin and pruritus in elderly</blockquote></li><ul> <li>Due to a decrease in skin lipids</li> </ul><li>Other age-related changes in elderly</li><ol type="a"> <li>Decreased number of hair follicles, sweat glands</li><li>Decrease in thickness of epidermis
<blockquote style="color: blue; ">Skin changes elderly: ↓ hair follicles, sweat glands, skin thickness</blockquote></li><li>Decreased dermal collagen/elastic tissue</li><li>Decreased subcutaneous fat</li><ul> <li>Example-over dorsum of hands</li> </ul><li>Increased cross-linking of collagen and elastic tissue
<blockquote style="color: blue; ">Skin changes in elderly: ↓ dermal collagen/elastic tissue but ↑ cross-linking</blockquote></li> </ol> </ol>
</div></html>
<html><a name="HC024044"></a> <br><a name="P024041"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common photodermatitis
<blockquote style="color: blue; ">PLE: most common photodermatitis</blockquote></li><li>Affects ∼10% of population</li><li>Positive family history</li><ul> <li>Very common in Native Americans</li> </ul><li>More common in women than men</li><li>More common in blacks than whites
<blockquote style="color: blue; ">PLE: common in Native Americans</blockquote></li><li>Rash has a rapid onset after sun exposure (<span>[[Fig. 24-8A|Figure 24-8]]</span>).</li><ol type="a"> <li>Erythematous macules, papules, plaques, or vesicles/bullae</li><li>Rash is pruritic and sometimes painful.</li><li><i>Not</i> related to drugs
<blockquote style="color: blue; ">PLE: rash occurs abruptly after sun exposure</blockquote></li> </ol><li>Treatment</li><ol type="a"> <li>Broad-spectrum high-potency sunscreen against UVA and UVB</li><ul> <li>Often vitamin E is added to the mixture or given as oral supplement.
<blockquote style="color: blue; ">PLE: rash begins with sun exposure</blockquote></li> </ul><li>Topical corticosteroids</li> </ol> </ol>
</div></html>
<html><a name="HC024045"></a> <br><a name="P024042"></a><div class="PA" style="color: black; "><ol type="1"> <li>Group of inflammatory dermatoses</li><ul> <li>Characterized by pruritus
<blockquote style="color: blue; ">Eczema: group of inflammatory dermatoses</blockquote></li> </ul><li>Acute eczema</li><ul> <li>Weeping, erythematous rash with vesicles</li> </ul><li>Chronic eczema
<blockquote style="color: blue; ">Eczema: acute weep; chronic dry</blockquote></li><ul> <li>Dry, thickened skin (hyperkeratosis) caused by continual scratching</li> </ul><li>Atopic dermatitis</li><ol type="a"> <li>Type I IgE-mediated hypersensitivity reaction</li><li>Dermatitis in children
<blockquote style="color: blue; ">Atopic dermatitis: type I IgE-mediated hypersensitivity</blockquote></li><ul> <li>Dry skin and eczema on cheeks and extensor and flexural surfaces (<span>[[Fig. 24-8B and C|Figure 24-8]]</span>)</li> </ul><li>Dermatitis in adults</li><ul> <li>Dry skin and eczema on hands, eyelids, elbows, and knees</li> </ul> </ol><li>Contact dermatitis</li><ol type="a"> <li>Allergic contact dermatitis
<blockquote style="color: blue; ">Contact dermatitis: type IV hypersensitivity; poison ivy, nickel in earrings</blockquote></li><ul> <li>(1) Type IV hypersensitivity reaction</li><li>(2) Examples-poison ivy (<span>[[Fig. 24-8D|Figure 24-8]]</span>), nickel in jewelry</li> </ul><li>Irritant contact dermatitis</li><ul> <li>Skin reaction to an irritant (e.g., laundry detergent)</li> </ul><li>Contact photodermatitis</li><ul> <li>(1) Ultraviolet light reacts with drugs that have a photosensitizing effect.
<blockquote style="color: blue; ">Tetracycline: drug with photosensitizing effect</blockquote></li><li>(2) Example-tetracycline</li> </ul> </ol><li>General treatment</li><ol type="a"> <li>Avoid drugs, irritants that produce a rash</li><li>Apply moistening agents (emollients) to skin</li><li>Topical corticosteroids</li><ul> <li>(1) Only low-potency hydrocortisone for the face</li><li>(2) Higher potency corticosteroids for other sites</li><ul> <li>(a) High-potency-clobetasol propionate, fluocinonide</li><li>(b) Medium-potency-clobetasone butyrate; triamcinolone</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC024046"></a> <br><a name="P024043"></a><div class="PA" style="color: black; "><ol type="1"> <li>Chronic cutaneous lupus erythematosus (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>)</li><ol type="a"> <li>Associated with atrophy of the epidermis</li><li>DNA-anti-DNA immunocomplex deposition in the basement membrane
<blockquote style="color: blue; ">Lupus skin involvement: immunocomplexes along basement membrane</blockquote></li><ul> <li>(1) Degeneration of basal cells and hair shafts (alopecia)</li><li>(2) Positive immunofluorescent (IF) band test</li><ul> <li>IF shows immunocomplexes deposited along the basement membrane.</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Erythematous maculopapular eruption</li><ul> <li>Usually over malar eminences and bridge of nose ("butterfly" rash) (see <span>[[Fig. 3-2A|Figure 3-2]]</span>)</li> </ul><li>(2) Skin lesions are exacerbated by UV light.</li> </ul><li>Antimalarials remain cornerstone of treatment.</li> </ol><li>Pemphigus vulgaris (PV)</li><ol type="a"> <li>IgG antibodies against intercellular attachment sites (desmosomes) between keratinocytes
<blockquote style="color: blue; ">PV: IgG antibodies against desmosomes between keratinocytes</blockquote></li><ul> <li>Type II hypersensitivity reaction</li> </ul><li>Vesicles and bullae develop on skin and oral mucosa.</li><li>Intraepithelial vesicles are located <i>above</i> the basal layer (suprabasal; <span>[[Fig. 24-8E|Figure 24-8]]</span>).
<blockquote style="color: blue; ">PV: intraepithelial vesicles; + Nikolsky sign; basal cells resemble tombstones</blockquote></li><ul> <li>(1) Basal cells resemble a row of tombstones.</li><li>(2) Acantholysis of keratinocytes in the vesicle fluid</li><li>(3) Positive Nikolsky sign</li><ul> <li>Outer epidermis separates from basal layer with minimal pressure</li> </ul> </ul><li>Treatment</li><ul> <li>Corticosteroids and other immunosuppressive agents (e.g., methotrexate, azathioprine)</li> </ul> </ol><li>Bullous pemphigoid
<blockquote style="color: blue; ">Bullous pemphigoid: IgG antibodies against basement membrane</blockquote></li><ol type="a"> <li>IgG antibodies against the basement membrane</li><ul> <li>Type II hypersensitivity reaction</li> </ul><li>Vesicles are subepidermal (<span>[[Fig. 24-8F|Figure 24-8]]</span>).
<blockquote style="color: blue; ">Bullous pemphigoid: subepidermal vesicles; - Nikolsky sign</blockquote></li><ul> <li>(1) Develop on the skin and oral mucosa (<span>[[Fig. 24-8G|Figure 24-8]]</span>)</li><li>(2) <i>No</i> acantholytic cells in vesicle fluid</li><li>(3) Negative Nikolsky sign</li> </ul><li>Disease usually subsides after months or years.
<blockquote style="color: blue; ">PV and bullous pemphigoid: type II hypersensitivity reactions</blockquote></li><li>May requires systemic corticosteroid in resistant cases</li> </ol><li>Dermatitis herpetiformis (DH; see <span>[[Fig. 17-19|Figure 17-19]]</span>)</li><ol type="a"> <li>IgA-anti-IgA complexes deposit at the tips of the dermal papillae.</li><ul> <li>Produces subepidermal vesicles with neutrophils
<blockquote style="color: blue; ">DH: associated with celiac disease; subepidermal vesicles with neutrophils</blockquote></li> </ul><li>Strongly correlated with celiac disease</li><ul> <li>Increase in antireticulin and endomysial antibodies</li> </ul><li>Treatment</li><ul> <li>(1) Gluten-free diet</li><li>(2) Dapsone or sulfapyridine</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC024047"></a> <br><a name="P024044"></a><div class="PA" style="color: black; "><ol type="1"> <li>Intensely pruritic, scaly, violaceous, flat-topped papules (<span>[[Fig. 24-8H|Figure 24-8]]</span>)
<blockquote style="color: blue; ">LP: pruritic; violaceous, flat-topped papules</blockquote></li><ol type="a"> <li>Fine white reticular pattern on the surface (called Wickham's striae)</li><li>Commonly located on the wrists, ankles</li><li>Nails are commonly dystrophic.</li><li>Lesions develop in areas of scratching (Koebner's phenomenon)</li> </ol><li>Women more commonly affected than men
<blockquote style="color: blue; ">LP: oral mucosa commonly involved; Wickham's striae</blockquote></li><li>Oral mucosa is often involved (50% of cases).</li><ol type="a"> <li>Produces a fine, white, net-like lesion (Wickham's striae)</li><li>Slight risk of developing squamous cell carcinoma</li> </ol><li>Association with hepatitis C
<blockquote style="color: blue; ">LP: associated with hepatitis C</blockquote></li><li>Treatment</li><ol type="a"> <li>Topical high-potency corticosteroids</li><li>Antihistamines (for pruritus)</li><li>Systemic corticosteroids</li><li>Retinoids</li><li>Cyclosporine in resistant cases</li> </ol> </ol>
</div></html>
<html><a name="HC024048"></a> <br><a name="P024045"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Afflicts 1% to 3% of the world population</li><li>Strong human leukocyte antigen (HLA) relationship
<blockquote style="color: blue; ">Psoriasis: strong HLA relationship</blockquote></li><li>Peak age at onset is bimodal.</li><ul> <li>Adolescents and 60 years of age</li> </ul><li>No gender difference</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Unregulated proliferation (hyperplasia) of keratinocytes
<blockquote style="color: blue; ">Psoriasis: unregulated proliferation of keratinocytes</blockquote></li><ul> <li>(1) Genetic factors involved (30% of cases)</li><li>(2) Aggravating factors</li><ul> <li>(a) Streptococcal pharyngitis
<blockquote style="color: blue; ">Psoriasis: commonly preceded by streptococcal pharyngitis</blockquote></li><li>(b) HIV</li><ul> <li>Sudden onset of psoriasis is highly suspicious for HIV</li> </ul><li>(c) Drugs: lithium, β-blockers, NSAIDs</li><li>(d) Scratching the skin (Koebner's phenomenon)</li> </ul> </ul><li>Microcirculatory changes in superficial papillary dermis</li> </ol><li>Well-demarcated, flat, elevated salmon-colored plaques (<span>[[Fig. 24-8I|Figure 24-8]]</span>)
<blockquote style="color: blue; ">Psoriasis: erythematous plaques with silver scales</blockquote></li><ol type="a"> <li>Covered by adherent white to silver-colored scales</li><ul> <li>Pinpoint areas of bleeding occur when scales are scraped off.</li> </ul><li>Rash commonly develops in areas of trauma (elbows, lower back).
<blockquote style="color: blue; ">Psoriasis: rash in areas of trauma (i.e., elbows); pitting of nails</blockquote></li><ul> <li>Called Koebner's phenomenon</li> </ul> </ol><li>Pitting of the nails (<span>[[Fig. 24-8J|Figure 24-8]]</span>)</li><li>Microscopic findings</li><ol type="a"> <li>Hyperkeratosis and parakeratosis</li><li>Elongation of rete pegs</li><ul> <li>Downward extensions of basal layer</li> </ul><li>Extension of the papillary dermis close to the surface epithelium</li><ul> <li>Blood vessels in dermis rupture when scales are picked off (Auspitz sign).</li> </ul><li>Neutrophil collections in the stratum corneum
<blockquote style="color: blue; ">Psoriasis: Munro microabscesses in stratum corneum: Auspitz sign</blockquote></li><ul> <li>Called Munro microabscesses</li> </ul> </ol><li>Treatment modalities</li><ol type="a"> <li>Topical high-potency corticosteroids</li><li>Topical calcipotriene (vitamin D analogue)</li><li>Ultraviolet light A plus psoralen applied to plaques</li><li>Ultraviolet light B plus coal tar applied to plaques</li><li>Retinoids</li><li>Systemic treatment</li><ul> <li>Methotrexate, cyclosporine</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC024049"></a> <br><a name="P024046"></a><div class="PA" style="color: black; "><ol type="1"> <li>Initially presents as a single, large, oval, scaly, rose-colored plaque on the trunk</li><ol type="a"> <li>Called the "herald patch"</li><li>Frequently misdiagnosed as tinea corporis ("ringworm")
<blockquote style="color: blue; ">Pityriasis rosea: herald patch (plaque) followed by rash in "Christmas tree" distribution</blockquote></li> </ol><li>Days or weeks later, a papular eruption develops on the trunk (<span>[[Fig. 24-8K|Figure 24-8]]</span>).</li><ol type="a"> <li>Rash follows the lines of cleavage ("Christmas tree" distribution).</li><li>Lesions tend to be pruritic.</li><li>Rash remits spontaneously in 2 to 10 weeks.</li> </ol><li>Antihistamines control pruritus; UV light therapy hastens resolution.</li> </ol>
</div></html>
<html><a name="HC024050"></a> <br><a name="P024047"></a><div class="PA" style="color: black; "><ol type="1"> <li>Immunologic reaction of skin</li><li>Triggered by:
<blockquote style="color: blue; ">EM: triggered by infection (<i>Mycoplasma</i>, HSV), drugs</blockquote></li><ol type="a"> <li>Infection</li><ul> <li><i>Mycoplasma pneumoniae,</i> herpes simplex virus (HSV; primary agent if recurrent EM occurs)</li> </ul><li>Drugs</li><ul> <li>Sulfonamides, penicillin, barbiturates, phenytoin
<blockquote style="color: blue; ">EM: rash has targetoid appearance; palmar involvement</blockquote></li> </ul> </ol><li>Vesicles and bullae have a "targetoid" appearance (<span>[[Fig. 24-8L|Figure 24-8]]</span>).</li><ul> <li>Located on the palms, soles, and extensor surfaces</li> </ul><li>Stevens-Johnson syndrome</li><ol type="a"> <li>EM that involves the skin and mucous membranes
<blockquote style="color: blue; ">EM: Stevens-Johnson syndrome involves skin and mucous membranes</blockquote></li><li>Can be fatal</li> </ol><li>Treatment</li><ol type="a"> <li>Treat with systemic corticosteroids</li><li>Treat triggering infection</li><li>Discontinue drug</li> </ol> </ol>
</div></html>
<html><a name="HC024051"></a> <br><a name="P024048"></a><div class="PA" style="color: black; "><ol type="1"> <li>Inflammatory lesion of subcutaneous fat (panniculitis)</li><li>More common in women than men
<blockquote style="color: blue; ">EN: panniculitis involving anterior portion of shins</blockquote></li><li>Raised, erythematous, painful nodules</li><ul> <li>Usually located on the anterior portion of the shins (<span>[[Fig. 24-8M|Figure 24-8]]</span>)</li> </ul><li>Common associations
<blockquote style="color: blue; ">EN: systemic fungal infections, TB, leprosy, sarcoid, pregnancy, OCPs</blockquote></li><ol type="a"> <li>Coccidioidomycosis, histoplasmosis</li><li>Tuberculosis, leprosy</li><li>Streptococcal pharyngitis</li><li><i>Yersinia</i> enterocolitis</li><li>Sarcoidosis, ulcerative colitis</li><li>Pregnancy, OCPs</li> </ol><li>Treatment</li><ol type="a"> <li>Identify and treat precipitating causes.</li><li>NSAIDs</li><li>Systemic corticosteroids if severe</li> </ol> </ol>
</div></html>
<html><a name="HC024052"></a> <br><a name="P024049"></a><div class="PA" style="color: black; "><ol type="1"> <li>Chronic inflammatory dermal disorder</li><ul> <li>Unknown etiology</li> </ul><li>Occurs in children and adults</li><ul> <li>Female predominance</li> </ul><li>Begin as erythematous papules</li><ul> <li>Papules evolve into annular plaques (<span>[[Fig. 24-8N|Figure 24-8]]</span>).</li> </ul><li>Occur on the dorsum of the hands and feet</li><ul> <li>Disseminated type may be associated with diabetes mellitus.
<blockquote style="color: blue; ">Granuloma annulare: association with diabetes mellitus</blockquote></li> </ul><li>Spontaneously resolve within 2 years</li><ul> <li>Recurrence in 40% of cases</li> </ul><li>Treatment</li><ol type="a"> <li>High-potency topical corticosteroids</li><li>Intralesional injection of corticosteroids</li> </ol> </ol>
</div></html>
<html><a name="HC024053"></a> <br><a name="P024050"></a><div class="PA" style="color: black; "><ol type="1"> <li>Genetic or acquired disease involving porphyrin metabolism
<blockquote style="color: blue; ">PCT: deficiency uroporphyrinogen decarboxylase; association with HCV, alcohol abuse</blockquote></li><li>Deficiency of uroporphyrinogen decarboxylase</li><ol type="a"> <li>Urine is wine-red color on voiding.</li><li>Uroporphyrin I is increased in urine.</li> </ol><li>Precipitating factors</li><ol type="a"> <li>Hepatitis C (HCV)</li><li>Excessive alcohol intake</li><li>OCPs</li><li>Iron</li> </ol><li>Clinical findings
<blockquote style="color: blue; ">Precipitating factors: HCV, alcohol abuse, OCPs, iron</blockquote></li><ol type="a"> <li>Photosensitive bullous skin lesions</li><ul> <li>(1) Caused by porphyrin metabolites deposited in the skin</li><li>(2) Patients avoid light.</li> </ul><li>Hyperpigmentation, fragile skin, hypertrichosis</li> </ol><li>Treatment</li><ol type="a"> <li>Avoid alcohol, OCPs</li><li>Phlebotomy (decrease iron)</li><li>Chloroquine</li> </ol> </ol>
</div></html>
<html><a name="HC024054"></a> <br><a name="P024051"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pruritic elevations of the skin
<blockquote style="color: blue; ">Urticaria: mast cell release of histamine</blockquote></li><ol type="a"> <li>Most often due to mast cell release of histamine</li><li>Type I IgE-mediated reactions associated with certain exposure:</li><ul> <li>(1) Certain foods (e.g., peanuts)</li><li>(2) Insect bites (e.g., fire ant)</li><li>(3) Drugs (e.g., penicillin, morphine, aspirin, laxative)</li><li>(4) Emotional stress</li><li>(5) Hepatitis B (part of serum sickness prodrome)</li><ul> <li>This is a type III hypersensitivity reaction.</li> </ul> </ul> </ol><li>Dermatographism (<span>[[Fig. 24-8O|Figure 24-8]]</span>)
<blockquote style="color: blue; ">Urticaria: may exhibit dermatographism</blockquote></li><ul> <li>Urticaria develops in areas of mechanical pressure on skin.</li> </ul><li>Treatment</li><ol type="a"> <li>Discontinue offending drug.</li><li>Avoid aspirin and other NSAIDs.</li><li>Antihistamines</li><li>Tricyclic drugs (e.g., doxepin)</li><li>Systemic steroids</li> </ol> </ol>
</div></html>
<html><a name="HC024055"></a> <br><a name="P024052"></a><div class="PA" style="color: black; "><ol type="1"> <li>Tiny, bright red papules (<span>[[Fig. 24-8P|Figure 24-8]]</span>)</li><ul> <li>Turn brown with time
<blockquote style="color: blue; ">Cherry angiomas: bright red papules; invariably present in elderly</blockquote></li> </ul><li>Invariably occur in all individuals > 30 years old.</li><li>No treatment is required.</li> </ol>
</div></html>
<html><a name="HC024056"></a> <br><a name="P024053"></a><div class="PA" style="color: black; "><ol type="1"> <li>Inflammatory reaction of the pilosebaceous units of facial skin
<blockquote style="color: blue; ">Acne rosacea: causal relationship with mite (<i>Demodex folliculorum</i>)</blockquote></li><ul> <li>Causal relationship with a mite (<i>Demodex folliculorum</i>)</li> </ul><li>Pustules and flushing of the cheeks (<span>[[Fig. 24-8Q|Figure 24-8]]</span>)</li><ul> <li>Exacerbated by drinking alcohol, stress, eating spicy foods</li> </ul><li>Sebaceous gland hyperplasia (<span>[[Fig. 24-8Q|Figure 24-8]]</span>)</li><ul> <li>Produces enlargement of the nose (rhinophyma)
<blockquote style="color: blue; ">Acne rosacea: pustules and flushing of cheeks; rhinophyma</blockquote></li> </ul><li>Treatment</li><ol type="a"> <li>Topical metronidazole gel</li><li>Systemic treatment</li><ul> <li>(1) Isotretinoin</li><li>(2) Tetracycline</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC024057"></a> <br><a name="P024054"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Ulcerative cutaneous condition often associated with systemic disease (>50%)
<blockquote style="color: blue; ">Pyoderma gangrenosum: ulcerative cutaneous disease associated with systemic disease</blockquote></li><li>Systemic disease associations</li><ul> <li>(1) Ulcerative colitis/Crohn's disease</li><li>(2) Myeloproliferative disease (MPD); monoclonal gammopathy</li><li>(3) Seronegative spondyloarthropathy
<blockquote style="color: blue; ">Pyoderma gangrenosum: ulcerative colitis/Crohn's disease; MPD; RA</blockquote></li><li>(4) Rheumatoid arthritis (RA)</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Probable dysregulation of immune system</li><li>Neutrophil dysfunction often present</li><li>Trauma may initiate the event (called pathergy).
<blockquote style="color: blue; ">Pyoderma gangrenosum: dysregulation of immune system</blockquote></li> </ol><li>Clinical findings</li><ol type="a"> <li>Small red pustule/papule that ulcerates and enlarges (<span>[[Fig. 24-8R|Figure 24-8]]</span>)</li><ul> <li>(1) Reminiscent of a brown recluse spider bite</li><li>(2) Single or multiple ulcers</li> </ul><li>Violaceous border overhangs ulcer crater.</li> </ol><li>Diagnosis</li><ol type="a"> <li>Culture to rule out secondary infection</li><li>Biopsy</li> </ol><li>Treatment</li><ol type="a"> <li>Topical-high-potency corticosteroids</li><li>Systemic-corticosteroids; tumor necrosis factor-α inhibitors, cyclosporine</li> </ol> </ol>
</div></html>
![[24.IX.A.Ichthyosis vulgaris]]
<<tiddler [[24.IX.A.Ichthyosis vulgaris]]>>
![[24.IX.B.Xerosis]]
<<tiddler [[24.IX.B.Xerosis]]>>
![[24.IX.C.Polymorphous light eruption (PLE)]]
<<tiddler [[24.IX.C.Polymorphous light eruption (PLE)]]>>
![[24.IX.D.Eczema]]
<<tiddler [[24.IX.D.Eczema]]>>
![[24.IX.E.Autoimmune skin disorders]]
<<tiddler [[24.IX.E.Autoimmune skin disorders]]>>
![[24.IX.F.Lichen planus (LP)]]
<<tiddler [[24.IX.F.Lichen planus (LP)]]>>
![[24.IX.G.Psoriasis]]
<<tiddler [[24.IX.G.Psoriasis]]>>
![[24.IX.H.Pityriasis rosea]]
<<tiddler [[24.IX.H.Pityriasis rosea]]>>
![[24.IX.I.Erythema multiforme (EM)]]
<<tiddler [[24.IX.I.Erythema multiforme (EM)]]>>
![[24.IX.J.Erythema nodosum (EN)]]
<<tiddler [[24.IX.J.Erythema nodosum (EN)]]>>
![[24.IX.K.Granuloma annulare]]
<<tiddler [[24.IX.K.Granuloma annulare]]>>
![[24.IX.L.Porphyria cutanea tarda (PCT)]]
<<tiddler [[24.IX.L.Porphyria cutanea tarda (PCT)]]>>
![[24.IX.M.Urticaria]]
<<tiddler [[24.IX.M.Urticaria]]>>
![[24.IX.N.Cherry angiomas]]
<<tiddler [[24.IX.N.Cherry angiomas]]>>
![[24.IX.O.Acne rosacea]]
<<tiddler [[24.IX.O.Acne rosacea]]>>
![[24.IX.P.Pyoderma gangrenosum]]
<<tiddler [[24.IX.P.Pyoderma gangrenosum]]>>
<html><a name="HC024021"></a> <br><a name="P024018"></a><div class="PA" style="color: black; "><ol type="1"> <li>Caused by <i>Ancyclostoma braziliense</i> (dog and cat hookworm; nematode)</li><ol type="a"> <li>Transmission</li><ul> <li>(1) Dogs and cats are the definitive host.
<blockquote style="color: blue; ">Cutaneous larva migrans: dog/cat hookworm (<i>Ancyclostoma</i>)</blockquote></li><ul> <li>Sexually mature host that can mate and lay eggs</li> </ul><li>(2) Larvae evolve in sand/soil from eggs passed in the feces.</li><li>(3) Larvae penetrate the skin in children/adults (intermediate hosts).</li> </ul><li>Cutaneous larva migrans (creeping eruption)
<blockquote style="color: blue; ">Cutaneous larva migrans: larvae penetrate skin; serpiginous tunnels</blockquote></li><ul> <li>(1) Larvae penetrate the skin.</li><ul> <li>(a) Commonly contracted while playing in sand</li><li>(b) Cover sandboxes so dogs/cat do not use them as litter boxes.</li> </ul><li>(2) Produce serpiginous tunnels in the skin (<span>[[Fig. 24-4A|Figure 24-4]]</span>)</li><ul> <li>Causes intense pruritus and scratching and eosinophilia</li> </ul><li>(3) Treatment is ivermectin.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC024022"></a> <br><a name="P024019"></a><div class="PA" style="color: black; "><ol type="1"> <li>Chiggers
<blockquote style="color: blue; ">Chigger: small, red mite</blockquote></li><ol type="a"> <li>Small, red to orange-colored mite</li><li>Produces a pruritic dermatitis
<blockquote style="color: blue; ">Chigger: intensely pruritic, red papular/urticarial/vesicular rash</blockquote></li><ul> <li>(1) Bright red papular, urticarial, or vesicular rash</li><li>(2) Favor the legs and areas of tight-fitting clothing</li> </ul><li>Treatment</li><ul> <li>Topical antipruritic agents (crotamiton and calamine lotion)</li> </ul> </ol><li>Human itch mite (<i>Sarcoptes scabiei</i> var. <i>hominis</i>)</li><ol type="a"> <li>Adult females bore into the stratum corneum.
<blockquote style="color: blue; ">Human itch mite: <i>Sarcoptes scabiei</i>; females burrow between fingers</blockquote></li><ul> <li>(1) Burrows are visible as dark lines between the fingers, at the wrists, on the nipples, or on the scrotum.</li><li>(2) Females lay eggs at the end of the tunnel.
<blockquote style="color: blue; ">Human itch mite: eggs cause pruritus</blockquote></li><ul> <li>Eggs are responsible for the intensely pruritic lesion.</li> </ul> </ul><li>Adults</li><ul> <li>(1) Disease limited to the webs between the fingers (<span>[[Fig. 24-4B|Figure 24-4]]</span>), intertriginous areas</li><li>(2) Spares the soles, palms, face and head
<blockquote style="color: blue; ">Human itch mite infants: no burrows; rash on palms, soles, face</blockquote></li> </ul><li>Infants</li><ul> <li>(1) <i>No</i> burrows are present.</li><li>(2) Pruritic rash occurs on the palms, soles, face or head.</li> </ul><li>Treatment is permethrin cream.</li> </ol> </ol>
</div></html>
<html><a name="HC024023"></a> <br><a name="P024020"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Head louse: <i>Pediculus humanis capitis;</i> lay eggs ("nits") on hair shafts</blockquote>
<ol type="1"> <li><i>Pediculus humanis capitis</i> (head louse)</li><ol type="a"> <li>Adults lay eggs ("nits") on hair shafts (<span>[[Fig. 24-4C|Figure 24-4]]</span>).</li><li>Itching of the scalp</li><li>Treatment</li><ul> <li>(1) Permethrin (kills newly hatched lice)
<blockquote style="color: blue; ">Body louse: <i>Pediculus hominis corporis;</i> adults live on skin and breed in clothing</blockquote></li><li>(2) Followed by lindane (Kwell), if the initial treatment is unsuccessful</li> </ul> </ol><li><i>Pediculus humanis corporis</i> (body louse)</li><ol type="a"> <li>Adults live on the surface of the skin and breed in the clothing.</li><li>Skin lesions are papular and produce intense itching (<span>[[Fig. 24-4D|Figure 24-4]]</span>).</li><li>Treat the clothing, <i>not</i> the patient.
<blockquote style="color: blue; ">Body louse: treat clothing <i>not</i> the patient</blockquote></li><ul> <li>Treat clothing with malathion or DDT powder or discard clothes</li> </ul> </ol><li><i>Phthirus pubis</i> (pubic louse, crabs)
<blockquote style="color: blue; "><i>Phthirus pubis:</i> louse; pubic hairs</blockquote></li><ol type="a"> <li>Adults live in the pubic hairs</li><ul> <li>Looks like a crab</li> </ul><li>Treatment is permethrin or malathion.</li> </ol> </ol>
</div></html>
<html><a name="HC024024"></a> <br><a name="P024021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Common bedbug is <i>Cimex lectularius</i>
<blockquote style="color: blue; ">Bedbug: <i>Cimex lectularius;</i> commonly infest dwellings; feed on human blood</blockquote></li><li>Commonly completely infest dwellings (houses, motels)</li><li>Feed on human blood</li><ol type="a"> <li>Active just before dawn</li><li>Attracted by warmth and CO<sub>2</sub></li> </ol><li>Skin lesions</li><ol type="a"> <li>Intensely pruritic red papules/wheals</li><li>Allergic reaction to anesthetic in saliva</li> </ol><li>Treatment</li><ul> <li>Exterminators use permethrin.</li> </ul> </ol>
</div></html>
![[24.V.A.Cutaneous larva migrans]]
<<tiddler [[24.V.A.Cutaneous larva migrans]]>>
![[24.V.B.Arthropod disorders: mites]]
<<tiddler [[24.V.B.Arthropod disorders: mites]]>>
![[24.V.C.Arthropod disorders: lice]]
<<tiddler [[24.V.C.Arthropod disorders: lice]]>>
![[24.V.D.Arthropod disorders: bedbug]]
<<tiddler [[24.V.D.Arthropod disorders: bedbug]]>>
<html><a name="HC024026"></a> <br><a name="P024023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Common finding in elderly individuals
<blockquote style="color: blue; ">Solar lentigo: common in elderly; "liver spots"; ↑ melanocytes</blockquote></li><li>Brown, macules located on sun-exposed areas ("liver spots") (<span>[[Fig. 24-5A|Figure 24-5]]</span>)</li><ol type="a"> <li>Increased number of melanocytes</li><li>In contradistinction, freckles have a normal number of melanocytes but an increase in melanosomes.
<blockquote style="color: blue; ">Freckles: normal number of melanocytes with increase in melanosomes</blockquote></li> </ol><li><i>Not</i> precancerous</li><li>No treatment</li> </ol>
</div></html>
<html><a name="HC024027"></a> <br><a name="P024024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Common in blacks</li><li>Autoimmune destruction of melanocytes
<blockquote style="color: blue; ">Vitiligo: autoimmune destruction of melanocytes</blockquote></li><ol type="a"> <li>Causes localized to extensive areas of skin depigmentation (<span>[[Fig. 24-5B|Figure 24-5]]</span>).</li><li>In contradistinction, albinism is due to a deficiency of tyrosinase leading to absence of melanin in melanocytes.
<blockquote style="color: blue; ">Albinism: deficiency of tyrosinase; absent melanin in melanocytes</blockquote></li> </ol><li>Often associated with other autoimmune conditions</li><ul> <li>Examples-Hashimoto's thyroiditis, hypoparathyroidism</li> </ul> </ol>
</div></html>
<html><a name="HC024028"></a> <br><a name="P024025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Macular, hyperpigmented lesions on the forehead and cheeks (<span>[[Fig. 24-5C|Figure 24-5]]</span>)</li><li>Female predominance; exacerbated (melanocytes produce more melanin) by:</li><ol type="a"> <li>Oral contraceptives (OCP)
<blockquote style="color: blue; ">Melasma: malar hyperpigmentation pregnancy/OCP</blockquote></li><li>Pregnancy ("pregnancy mask")</li><li>Sunlight</li> </ol><li>Treatment</li><ul> <li>Application of hydroquinone (bleaching agent) to skin</li> </ul> </ol>
</div></html>
<html><a name="HC024029"></a> <br><a name="P024026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Neoplastic melanocytic disorder</li><li>Whites have an average of 15 to 40 nevi on their skin.</li><li>Frequently contain hair
<blockquote style="color: blue; ">Nevus cells: modified melanocytes</blockquote></li><li>Benign tumor of neural crest-derived nevus cells</li><ul> <li>Nevus cells are modified melanocytes.</li> </ul><li>Begins in early childhood as junctional nevus (<span>[[Fig. 24-5D|Figure 24-5]]</span>)</li><ol type="a"> <li>Pigmented macular (flat) lesion</li><li>Nests of nevus cells occur along the basal cell layer.</li> </ol><li>Junctional nevus develops into a compound nevus.</li><ol type="a"> <li>Usually occurs in children and adolescents
<blockquote style="color: blue; ">Junctional nevus: most common nevus in children</blockquote></li><li>Nevus cells extend into the superficial dermis.</li><ul> <li>Junctional and intradermal components are present.</li> </ul><li>Pigmented lesion with a papillomatous surface (<span>[[Fig. 24-5E|Figure 24-5]]</span>)</li> </ol><li>Intradermal nevus
<blockquote style="color: blue; ">Intradermal nevus: most common nevus in adults</blockquote></li><ul> <li>Develop when a compound nevus loses its junctional component (<span>[[Fig. 24-5F|Figure 24-5]]</span>)</li> </ul><li>Dysplastic nevus (atypical mole)</li><ol type="a"> <li>May arise sporadically</li><ul> <li>(1) Controversial on whether they may develop into a malignant melanoma
<blockquote style="color: blue; ">Dysplastic nevus syndrome: majority develop malignant melanoma</blockquote></li><li>(2) Usually >6 mm; variegated in color with an erythematous background; irregular borders</li> </ul><li>May be associated with the dysplastic nevus syndrome (<span>[[Fig. 24-5G|Figure 24-5]]</span>)</li><ul> <li>(1) Autosomal dominant syndrome with >100 nevi on the skin</li><li>(2) Dysplastic nevi in this syndrome can develop into malignant melanomas.</li><ul> <li>Virtually all members in the family with this syndrome will develop melanomas.</li> </ul><li>(3) All patients require a yearly dermatologic examination.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC024030"></a> <br><a name="P024027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology
<blockquote style="color: blue; ">Melanoma: leading cause of death due to skin cancer</blockquote></li><ol type="a"> <li>Malignant tumor of melanocytes</li><li>Most rapidly increasing cancer worldwide</li><ul> <li>More common in whites than blacks
<blockquote style="color: blue; ">Melanoma: most rapidly increasing cancer worldwide</blockquote></li> </ul> </ol><li>Leading cause of death due to skin cancer</li><li>Median age at diagnosis is 53 years.</li><li>Risk factors</li><ol type="a"> <li>Exposure to excessive sunlight (UVA and UVB) at an early age</li><ul> <li>Single most important risk factor
<blockquote style="color: blue; ">Malignant melanoma: exposure to excessive sunlight at early age most significant risk factor</blockquote></li> </ul><li>History of a family member with melanoma</li><li>Use of tanning booths</li><li>Dysplastic nevus syndrome</li><li>History of melanoma in first- or second-degree relative</li><li>Xeroderma pigmentosum (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>)
<blockquote style="color: blue; ">Radial growth phase: initial phase of invasion; spread laterally in papillary dermis; no metastatic potential</blockquote></li> </ol><li>Radial growth phase</li><ol type="a"> <li>Initial phase of invasion</li><li>Melanocytes proliferate</li><ul> <li>(1) Laterally within the epidermis</li><li>(2) Along the dermoepidermal junction</li><li>(3) Within the papillary dermis
<blockquote style="color: blue; ">Vertical growth phase: final phase of invasion; penetrate reticular dermis; metastatic potential</blockquote></li> </ul><li><i>No</i> metastatic potential in this phase</li> </ol><li>Vertical growth phase</li><ol type="a"> <li>Final phase of invasion</li><li>Malignant cells penetrate the underlying reticular dermis.
<blockquote style="color: blue; ">ABCD signs of melanoma: <i>a</i>symmetry; <i>b</i>orders irregular; <i>c</i>olor changes; <i>d</i>iameter increased</blockquote></li><li>Potential for metastasis</li> </ol><li>Types of malignant melanoma</li><ol type="a"> <li>Superficial spreading melanoma (<span>[[Fig. 24-5H|Figure 24-5]]</span>)</li><ul> <li>(1) Most common type (70% of cases)
<blockquote style="color: blue; ">Superficial spreading melanoma: most common type of malignant melanoma</blockquote></li><li>(2) Develops on lower extremities, arms, and upper back</li> </ul><li>Lentigo maligna melanoma (4-10% of cases)</li><ul> <li>(1) Common in the elderly population</li><li>(2) Extension of lentigo maligna (intraepidermal lesion) into the dermis
<blockquote style="color: blue; ">Lentigo maligna melanoma: elderly; occurs on face; least likely to have vertical phase</blockquote></li><li>(3) Occurs on parts of the face most exposed to the sun (<span>[[Fig. 24-5I|Figure 24-5]]</span>)</li><li>(4) <i>Least</i> likely to have a vertical phase</li> </ul><li>Nodular melanoma (15-30% of cases)</li><ul> <li>(1) <i>No</i> radial growth phase</li><li>(2) Can be found in any sun-exposed area</li><ul> <li>Most often the trunk</li> </ul><li>(3) No radial phase only vertical phase
<blockquote style="color: blue; ">Nodular melanoma: no radial phase only vertical phase</blockquote></li><li>(4) Poor prognosis</li> </ul><li>Acral lentiginous melanoma (2-8% of cases)</li><ul> <li>(1) <i>Not</i> related to sun exposure
<blockquote style="color: blue; ">Acral lentiginous melanoma: not UV related; palms/soles; Asians and blacks</blockquote></li><li>(2) Located on the palm, sole, or beneath the nail (<span>[[Fig. 24-5J|Figure 24-5]]</span>)</li><ul> <li>Often confused with a subungual hematoma</li> </ul><li>(3) Most often occurs in Asians and blacks</li><li>(4) Poor prognosis</li> </ul> </ol><li>Depth of invasion best determines biologic behavior.
<blockquote style="color: blue; ">Prognosis in malignant melanoma: depth of invasion most important</blockquote></li><li>ABCD criteria for malignancy (<span>[[Fig. 24-5K|Figure 24-5]]</span>)</li><ol type="a"> <li>Asymmetry of shape</li><li>Border irregularity</li><li>Color variation</li><li>Diameter > 6 mm</li> </ol><li>Prevention</li><ol type="a"> <li>Sunscreen > 15 SPF (controversial)
<blockquote style="color: blue; ">Melanoma prevention: sunscreen > 15 SPF</blockquote></li><ul> <li>Prevention for UVA and UVB light</li> </ul><li>Protective clothing</li> </ol><li>Treatment</li><ol type="a"> <li>Excision of entire lesion and surrounding normal tissue</li><ul> <li>Sentinel lymph node biopsy to determine stage</li> </ul><li>More extensive disease</li><ul> <li>Immunotherapy; irradiation</li> </ul> </ol> </ol>
</div></html>
![[24.VI.A.Solar lentigo]]
<<tiddler [[24.VI.A.Solar lentigo]]>>
![[24.VI.B.Vitiligo]]
<<tiddler [[24.VI.B.Vitiligo]]>>
![[24.VI.C.Melasma]]
<<tiddler [[24.VI.C.Melasma]]>>
![[24.VI.D.Nevocellular nevus (mole)]]
<<tiddler [[24.VI.D.Nevocellular nevus (mole)]]>>
![[24.VI.E.Malignant melanoma]]
<<tiddler [[24.VI.E.Malignant melanoma]]>>
<html><a name="HC024032"></a> <br><a name="P024029"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology
<blockquote style="color: blue; ">Seborrheic keratosis: most common benign tumor in older people</blockquote></li><ol type="a"> <li>Most common benign tumor in older people</li><li>Occurs in individuals > 50 years of age</li> </ol><li>Benign pigmented epidermal tumor (<span>[[Fig. 24-6A|Figure 24-6]]</span>)</li><ol type="a"> <li>Coin-like, macular to raised verrucoid lesion with "stuck-on" appearance</li><li>Extremities and shoulders most common sites</li><li>Occur commonly on the face in elderly patients</li> </ol><li>Leser-Trélat sign (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>)
<blockquote style="color: blue; ">Leser-Trélat sign: phenotypic marker for stomach adenocarcinoma</blockquote></li><ol type="a"> <li>Rapid increase in number of keratoses</li><li>Phenotypic marker for stomach adenocarcinoma</li> </ol><li>Treatment</li><ol type="a"> <li>Cryotherapy</li><li>Curettage</li><li>Shave biopsy/excision</li> </ol> </ol>
</div></html>
<html><a name="HC024033"></a> <br><a name="P024030"></a><div class="PA" style="color: black; "><ol type="1"> <li>Velvety, pigmented skin lesion
<blockquote style="color: blue; ">AN: velvety pigmented lesion; common in axilla</blockquote></li><li>Commonly located in the axilla (<span>[[Fig. 24-6B|Figure 24-6]]</span>)</li><ol type="a"> <li>Other sites-neck, axilla, groin, under breasts</li> </ol><li>Pathogenesis</li><ul> <li>Excess insulin noted in many cases</li> </ul><li>Associations</li><ol type="a"> <li>Metabolic syndrome (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li><ul> <li>Obesity association important because of insulin resistance (down-regulation of insulin receptors)
<blockquote style="color: blue; ">AN associations: metabolic syndrome; insulin receptor deficiency; POS; stomach cancer</blockquote></li> </ul><li>Insulin receptor deficiency</li><li>Polycystic ovary syndrome (POS; refer to <span macro="tag [[21 Female Reproductive Disorders and Breast Disorders]] [[Chapter 21]]"></span>)</li><li>Phenotypic marker for gastric cancer (refer to <span macro="tag [[08 Neoplasia]] [[Chapters 8]]"></span> and <span macro="tag [[17 Gastrointestinal Disorders]] [[17]]"></span>)</li><li>Multiple endocrine neoplasia syndrome IIb</li> </ol><li>Treatment</li><ol type="a"> <li>Treating underlying condition causes some regression</li><li>Topical tretinoin</li> </ol> </ol>
</div></html>
![[24.VII.A.Seborrheic keratosis]]
<<tiddler [[24.VII.A.Seborrheic keratosis]]>>
![[24.VII.B.Acanthosis nigricans (AN)]]
<<tiddler [[24.VII.B.Acanthosis nigricans (AN)]]>>
![[24.VII.C.Keratoacanthoma (KA)]]
<<tiddler [[24.VII.C.Keratoacanthoma (KA)]]>>
![[24.VII.D.Benign epidermal cysts]]
<<tiddler [[24.VII.D.Benign epidermal cysts]]>>
![[24.VII.E.Fibroepithelial polyp (tag)]]
<<tiddler [[24.VII.E.Fibroepithelial polyp (tag)]]>>
<html><a name="HC024034"></a> <br><a name="P024031"></a><div class="PA" style="color: black; "><ol type="1"> <li>Male predominance
<blockquote style="color: blue; ">KA: benign tumor that histologically mimics squamous cancer</blockquote></li><li>Rapidly growing, benign crateriform tumor with a central keratin plug (<span>[[Fig. 24-6C|Figure 24-6]]</span>)</li><ol type="a"> <li>Grows within 4 to 6 weeks
<blockquote style="color: blue; ">KA: appears within 4-6 weeks; disappears within 6 months</blockquote></li><li>Develops in sun-exposed areas</li><li>Mimics a well-differentiated squamous cell carcinoma</li> </ol><li>Regresses spontaneously with scarring usually within 6 months</li><li>Excision is recommended.</li> </ol>
</div></html>
<html><a name="HC024035"></a> <br><a name="P024032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidermal inclusion cysts (follicular cyst)
<blockquote style="color: blue; ">Epidermal inclusion cyst: derives from epidermis of hair follicle</blockquote></li><ol type="a"> <li>Derived from the epidermis of the hair follicle (<span>[[Fig. 24-6D|Figure 24-6]]</span>)</li><li>Locations</li><ul> <li>Face, base of ears, and trunk</li> </ul><li>Cyst wall composed of normal epidermis that produces keratin
<blockquote style="color: blue; ">Locations: face, base of ears, trunk</blockquote></li><ul> <li>Keratin intermixed with lipid-rich debris</li> </ul><li>Spontaneous inflammation and rupture may occur.</li><li>Treatment</li><ul> <li>None required; surgical excision if necessary</li> </ul> </ol><li>Pilar cyst (wen)</li><ol type="a"> <li>Derived from hair root sheaths
<blockquote style="color: blue; ">Pilar cyst: derives from hair root sheaths</blockquote></li><li>Located on the scalp and face (<span>[[Fig. 24-6E|Figure 24-6]]</span>)</li><li>Cyst wall lacks stratum granulosum.
<blockquote style="color: blue; ">Pilar cyst: located on scalp and face</blockquote></li><ul> <li>Keratin has a laminated appearance.</li> </ul><li>Spontaneous inflammation and rupture may occur.</li><li>Treatment</li><ul> <li>Usually none required; surgical excision if necessary</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC024036"></a> <br><a name="P024033"></a><div class="PA" style="color: black; "><ol type="1"> <li>Flesh-colored soft tag of skin attached to the body by a narrow stalk (<span>[[Fig. 24-6F|Figure 24-6]]</span>)</li><li>Common finding in the elderly
<blockquote style="color: blue; ">Fibroepithelial tag: flesh-colored tag of skin with a stalk; common in elderly</blockquote></li><li>Locations</li><ul> <li>Neck, upper chest, upper back</li> </ul><li>Treatment</li><ul> <li>None required; excise if necessary</li> </ul> </ol>
</div></html>
<html><a name="HC024038"></a><span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span> <br> <br><a name="P024035"></a><div class="PA" style="color: black; "><ol type="1"> <li>Associated with prolonged ultraviolet light exposure
<blockquote style="color: blue; ">Actinic (solar) keratosis: squamous dysplasia; precursor for squamous cancer</blockquote></li><li>Precursor (squamous dysplasia) of squamous cell carcinoma</li><ul> <li>Squamous cancer occurs in 2% to 5% of cases.</li> </ul><li>Hyperkeratotic, pearly gray-white appearance
<blockquote style="color: blue; ">Actinic (solar) keratosis: lesions recur after being scraped off.</blockquote></li><ol type="a"> <li>Occurs on face, back of neck, dorsum of hands/forearms (<span>[[Fig. 24-7A|Figure 24-7]]</span>)</li><li>Commonly recurs when scraped off</li> </ol><li>Treatment</li><ol type="a"> <li>Protection of skin with sunscreen</li><li>Topical therapy-5-fluorouracil</li><li>Cryotherapy</li> </ol> </ol>
</div></html>
<html><a name="HC024039"></a> <br><a name="P024036"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">BCC: most common malignant skin tumor</blockquote>
<ol type="1"> <li>Caused by chronic exposure to ultraviolet light</li><li>Raised papule or nodule with a central crater (<span>[[Fig. 24-7B|Figure 24-7]]</span>)</li><ul> <li>Sides of the crater are surfaced by telangiectatic vessels.</li> </ul><li>Occurs in sun-exposed areas
<blockquote style="color: blue; ">BCC: invade but do not metastasize</blockquote></li><ol type="a"> <li>Inner canthus of the eye, upper lip</li><li>Very general rule of thumb is that BCCs favor upper lip and higher.</li> </ol><li>Locally aggressive, infiltrating cancer that does <i>not</i> metastasize</li><ol type="a"> <li>Tumor is stromal dependent, hence precluding metastasis.</li><li>Arises from the basal cell layer of the epidermis</li><li>Multifocal in origin</li><ul> <li>This makes it difficult to get free margins after surgery
<blockquote style="color: blue; ">BCC: arise from basal cell layer</blockquote></li> </ul><li>Cords of basophilic-staining basal cells infiltrate the underlying dermis (<span>[[Fig. 24-7C|Figure 24-7]]</span>).</li> </ol><li>Diagnosis</li><ul> <li>Punch biopsy or shave biopsy</li> </ul><li>Treatment</li><ol type="a"> <li>Varies with location and size of the cancer</li><li>Options include topical 5-fluorouracil, cryotherapy, curettage and electrodesiccation, surgical excision, radiation (usually in elderly).</li> </ol> </ol>
</div></html>
<html><a name="HC024040"></a> <br><a name="P024037"></a><div class="PA" style="color: black; "><ol type="1"> <li>Risk factors</li><ol type="a"> <li>Excessive exposure to ultraviolet light (most common)
<blockquote style="color: blue; ">SCC: excessive exposure to UV light; actinic keratosis; scar tissue</blockquote></li><li>Actinic (solar) keratosis</li><li>Arsenic exposure</li><li>Scar tissue in a third-degree burn
<blockquote style="color: blue; ">SCC: most common cancer complicating immunosuppressive therapy</blockquote></li><li>Orifice of chronically draining sinus tract</li><li>Immunosuppressive therapy</li> </ol><li>Scaly to nodular lesions</li><ol type="a"> <li>Nodules are often ulcerated.</li><li>Majority occur in sun-exposed areas of the body.</li><ul> <li>(1) Examples-ears (<span>[[Fig. 24-7D|Figure 24-7]]</span>), lower lip (see <span>[[Fig. 17-7|Figure 17-7]]</span>), dorsum of the hands</li><li>(2) Very general rule of thumb is that SCCs favor lower lip.
<blockquote style="color: blue; ">SCCs favor lower lip; BCCs favor upper lip</blockquote></li> </ul><li>Usually well differentiated</li><ul> <li>Minimal risk for metastasis</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Varies with location and size of the cancer</li><li>Options include topical 5-fluorouracil, cryotherapy, curettage and electrodesiccation, surgical excision, radiation (usually in elderly).</li> </ol> </ol>
</div></html>
![[24.VIII.A.Actinic (solar) keratosis (refer to Chapter 8)]]
<<tiddler [[24.VIII.A.Actinic (solar) keratosis (refer to Chapter 8)]]>>
![[24.VIII.B.Basal cell carcinoma (BCC)]]
<<tiddler [[24.VIII.B.Basal cell carcinoma (BCC)]]>>
![[24.VIII.C.Squamous cell carcinoma (SCC)]]
<<tiddler [[24.VIII.C.Squamous cell carcinoma (SCC)]]>>
<html><a name="HC024059"></a> <br><a name="P024056"></a><div class="PA" style="color: black; "><ol type="1"> <li>Self-limited benign eruption of unknown cause
<blockquote style="color: blue; ">Erythema toxicum: 30-70% newborns; self-limited</blockquote></li><ol type="a"> <li>Occurs in 30% to 70% of full-term newborns (<i>not</i> premature newborns)</li><li>Lasts 2 to 3 weeks</li> </ol><li>Erythematous papules, macules, and pustules (<span>[[Fig. 24-9A|Figure 24-9]]</span>)</li><li>Locations</li><ul> <li>All sites <i>except</i> palms and soles
<blockquote style="color: blue; ">Sebaceous hyperplasia: yellow-white papules on face; self-limited</blockquote></li> </ul> </ol>
</div></html>
<html><a name="HC024060"></a> <br><a name="P024057"></a><div class="PA" style="color: black; "><ol type="1"> <li>Profuse yellow-white papules</li><ol type="a"> <li>Hyperplastic sebaceous glands</li><li>Disappear in first weeks of life</li> </ol><li>Locations</li><ul> <li>Forehead, nose (<span>[[Fig. 24-9B|Figure 24-9]]</span>), upper lip, cheeks</li> </ul> </ol>
</div></html>
<html><a name="HC024061"></a> <br><a name="P024058"></a><div class="PA" style="color: black; "><ol type="1"> <li>Superficial epidermal inclusion cysts</li><ul> <li>Pearly white papules contain laminated keratin material.
<blockquote style="color: blue; ">Milia: superficial epidermal inclusion cysts; pearly white papules</blockquote></li> </ul><li>Location in neonates</li><ul> <li>Face (<span>[[Fig. 24-9C|Figure 24-9]]</span>), gingiva, midline of palate and gingiva (called Epstein's pearls)</li> </ul><li>Exfoliate spontaneously or can be unroofed with fine needle
<blockquote style="color: blue; ">Milia: called Epstein's pearls when in mouth</blockquote></li> </ol>
</div></html>
<html><a name="HC024062"></a> <br><a name="P024059"></a><div class="PA" style="color: black; "><ol type="1"> <li>Miliaria crystallina
<blockquote style="color: blue; ">Miliaria crystallina: pinpoint clear vesicles; sweat in occluded sweat glands</blockquote></li><ol type="a"> <li>Pinpoint clear vesicles on skin</li><li>Retention of sweat in occluded eccrine sweat glands</li><li>May suddenly erupt in profusion over large areas of the body (<span>[[Fig. 24-9D|Figure 24-9]]</span>)</li><li>Often associated in warm, humid conditions or fever</li><li>Responds dramatically to cooling the patient and removal of excess clothing</li> </ol><li>Miliaria rubra ("prickly heat")
<blockquote style="color: blue; ">Miliaria rubra: prickly heat; erythematous papulovesicles</blockquote></li><ol type="a"> <li>Retention of sweat in occluded eccrine glands</li><li>Erythematous, minute papulovesicles that impart a prickly sensation (<span>[[Fig. 24-9E|Figure 24-9]]</span>)</li><li>Like miliaria crystallina, it responds dramatically to cooling</li> </ol> </ol>
</div></html>
<html><a name="HC024063"></a> <br><a name="P024060"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Both types of miliaria respond to cooling</blockquote>
<ol type="1"> <li>Bluish black to slate gray spots
<blockquote style="color: blue; ">Mongolian spot: bluish black to gray spot; dark-skinned babies</blockquote></li><li>Usually occur in dark-skinned babies</li><li>Locations</li><ol type="a"> <li>Buttocks (<span>[[Fig. 24-9F|Figure 24-9]]</span>), back, shoulders, legs</li> </ol><li>Disappears in the preschool years
<blockquote style="color: blue; ">Mongolian spot: disappears in preschool years</blockquote></li> </ol>
</div></html>
![[24.X.A.Erythema toxicum]]
<<tiddler [[24.X.A.Erythema toxicum]]>>
![[24.X.B.Sebaceous hyperplasia]]
<<tiddler [[24.X.B.Sebaceous hyperplasia]]>>
![[24.X.C.Milia]]
<<tiddler [[24.X.C.Milia]]>>
![[24.X.D.Miliaria]]
<<tiddler [[24.X.D.Miliaria]]>>
![[24.X.E.Mongolian spot]]
<<tiddler [[24.X.E.Mongolian spot]]>>
<html><a name="HC024065"></a> <br><a name="P024062"></a><div class="PA" style="color: black; "><ol type="1"> <li>Anagen phase
<blockquote style="color: blue; ">Anagen phase: new hair shaft; hair length determined</blockquote></li><ol type="a"> <li>Development of new shaft of hair comes from hair bulb.</li><li>Hair length is determined in this stage.</li><li>Growth stops at end of this phase.</li> </ol><li>Telogen phase
<blockquote style="color: blue; ">Telogen phase: resting phase; loss of hair</blockquote></li><ol type="a"> <li>Resting phase</li><li>Matrix portion shrivels and hair within the follicle is shed.</li><li>New matrix is formed at the bottom of the follicle.</li><li>Cycle repeats itself.</li> </ol><li>Length of each phase varies in the body.</li><ul> <li>Scalp hair-anagen phase 6 years, telogen phase 4 months</li> </ul><li>Hair growth is usually asynchronous; for scalp hair:</li><ol type="a"> <li>At any one time, ∼80% is in anagen phase; ∼10% to 20% is in telogen phase.</li><li>Only a small percentage of hair is lost at any point in time.</li> </ol><li>Estrogen effect on hair growth
<blockquote style="color: blue; ">Estrogen: causes synchronous hair growth; risk for massive hair loss</blockquote></li><ol type="a"> <li>Causes synchronous hair growth</li><li>All the hairs enter the resting phase at once.</li> </ol> </ol>
</div></html>
<html><a name="HC024066"></a> <br><a name="P024063"></a><div class="PA" style="color: black; "><ol type="1"> <li>Post partum</li><ul> <li>Most common cause</li> </ul><li>Oral contraceptive pills
<blockquote style="color: blue; ">Massive hair loss: postpartum; OCPs; stress; radiation/chemotherapy</blockquote></li><li>Stress</li><li>Radiation/chemotherapy</li><ul> <li>Inhibition of anagen phase when cells in the hair bulb are dividing</li> </ul> </ol>
</div></html>
<html><a name="HC024067"></a> <br><a name="P024064"></a><div class="PA" style="color: black; "><ol type="1"> <li>Affects both sexes equally</li><li>Onset most commonly in young adults</li><li>Cause is not known.</li><ol type="a"> <li>May have an autoimmune association in some cases</li><ul> <li>Hashimoto's thyroiditis, pernicious anemia</li> </ul><li>Family history in 20% to 25% of patients</li> </ol><li>Clinical findings
<blockquote style="color: blue; ">Alopecia areata: hairs in areas of hair loss have appearance of exclamation marks</blockquote></li><ol type="a"> <li>Well-circumscribed, round to oval patches of hair loss</li><ul> <li>Hair loss may occur on scalp, beard, eyebrows, eyelashes.</li> </ul><li>Hairs have the appearance of exclamation marks (<span>[[Fig. 24-10A|Figure 24-10]]</span>).</li><li>Hair loss occurs over a period of weeks.</li><li>Regrowth of hair occurs over several months.</li><li>May recur in up to one third of cases</li> </ol><li>Treatment</li><ol type="a"> <li>Topical-clobetasol</li><li>Intralesional triamcinolone</li><li>Systemic corticosteroids</li><li>Psoralen + UVA, immunotherapy</li> </ol> </ol>
</div></html>
<html><a name="HC024068"></a> <br><a name="P024065"></a><div class="PA" style="color: black; "><ol type="1"> <li>Nail anatomy (<span>[[Fig. 24-10B|Figure 24-10]]</span>)
<blockquote style="color: blue; ">Nail anatomy: lunula, nail plate, nail matrix</blockquote></li><ol type="a"> <li>Lunula</li><ul> <li>(1) White half-moon-shaped area proximal to the cuticle</li><li>(2) Underlying nail bed is partially keratinized, which produces the white color.</li> </ul><li>Nail plate</li><ul> <li>Attached to the nail bed <i>except</i> distally where it separates from the hyponychium</li> </ul><li>Nail matrix</li><ul> <li>(1) Underneath the cuticle (eponychium)</li><li>(2) Germinative zone where the nail plate originates</li> </ul> </ol><li>Nail disorders
<blockquote style="color: blue; ">Psoriasis: nail pitting</blockquote></li><ol type="a"> <li>Psoriasis (see <span>[[Fig. 24-8J|Figure 24-8]]</span>)</li><ul> <li>Greater than 80% have nail pitting.
<blockquote style="color: blue; ">Iron deficiency: koilonychia (spoon nails)</blockquote></li> </ul><li>Iron deficiency</li><ul> <li>Koilonychia (spoon nails; see <span>[[Fig. 11-10|Figure 11-10]]</span>)</li> </ul><li>Subacute infective endocarditis and trichinosis
<blockquote style="color: blue; ">Splinter hemorrhages: subacute infective endocarditis; trichinosis</blockquote></li><ul> <li>Splinter hemorrhages in nails (see <span>[[Fig. 10-21|Figure 10-21]]</span>)</li> </ul><li>Mees lines
<blockquote style="color: blue; ">Mees lines: transverse white lines; arsenic poisoning; systemic illness</blockquote></li><ul> <li>(1) Sign of arsenic poisoning and systemic illness of any kind</li><li>(2) Transverse white lines in the nail plate (<span>[[Fig. 24-10C|Figure 24-10]]</span>)</li><ul> <li>Extend proximally until they are pared off</li> </ul> </ul><li>Beau's lines
<blockquote style="color: blue; ">Beau's lines: transverse grooves parallel to lunula; infections</blockquote></li><ul> <li>(1) Transverse grooves or depressions parallel to lunula (<span>[[Fig. 24-10D|Figure 24-10]]</span>)</li><li>(2) Caused by conditions that cause the nail to grow slowly</li><ul> <li>Examples-infections, nutritional disorders, hypothyroidism</li> </ul> </ul><li>Subungual hematoma
<blockquote style="color: blue; ">Subungual hematoma: blood clot under nail plate; confused with acral lentiginous melanoma</blockquote></li><ul> <li>(1) Blood clot under the nail plate due to trauma</li><li>(2) Often confused with acral lentiginous melanoma</li> </ul> </ol> </ol>
</div></html>
![[24.XI.A.Phases of hair growth in succession]]
<<tiddler [[24.XI.A.Phases of hair growth in succession]]>>
![[24.XI.B.Massive hair loss]]
<<tiddler [[24.XI.B.Massive hair loss]]>>
![[24.XI.C.Alopecia areata]]
<<tiddler [[24.XI.C.Alopecia areata]]>>
![[24.XI.D.Nail disorders]]
<<tiddler [[24.XI.D.Nail disorders]]>>
<html><a name="HC025002"></a> <br><a name="PB025001"></a><div class="BB" style="color: rgb(47, 79, 79); ">A patient with <b>head trauma</b> is purposely hyperventilated to produce respiratory alkalosis, which causes cerebral vessel constriction. This decreases the risk of increased vessel permeability and cerebral edema. Respiratory acidosis and hypoxemia cause vasodilation of cerebral vessels, which increases cerebral vessel permeability, resulting in cerebral edema. Both conditions cause increased activity of the K<sup>+</sup> channels in smooth muscle cells → produces hyperpolarization → relaxes smooth muscle cells (↓ intracellular calcium) producing vasodilation with increased vessel permeability.
<blockquote style="color: blue; ">Respiratory acidosis, hypoxemia: ↑ cerebral vessel permeability; enhance cerebral edema</blockquote></div><a name="P025001"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Cerebral edema: intracellular and extracellular types</blockquote>
<ol type="1"> <li>Subdivided into intracellular and extracellular types (<span>[[Fig. 25-1|Figure 25-1]]</span>)</li><li>Intracellular edema
<blockquote style="color: blue; ">Intracellular: ↓ serum Na<sup>+</sup> (SIADH); dysfunctional Na<sup>+</sup>/K<sup>+</sup>-ATPase pump (global hypoxia)</blockquote></li><ol type="a"> <li>Water moves into cells.</li><li>Causes</li><ul> <li>(1) Dysfunctional Na<sup>+</sup>/K<sup>+</sup>-ATPase pump (e.g., global hypoxia)</li><li>(2) Hyponatremia causing osmotic shift (e.g., syndrome of inappropriate antidiuretic hormone, SIADH)</li> </ul> </ol><li>Extracellular edema
<blockquote style="color: blue; ">Extracellular: ↑ vessel permeability; meningitis, metastasis</blockquote></li><ol type="a"> <li>Due to increased vessel permeability (vasogenic)</li><li>Causes</li><ul> <li>(1) Acute inflammation (e.g., meningitis, encephalitis)</li><li>(2) Metastasis, trauma, lead poisoning</li> </ul> </ol><li>Produces signs of increased intracranial pressure (intracranial hypertension)</li><ol type="a"> <li>Papilledema
<blockquote style="color: blue; ">Papilledema: sign of cerebral edema</blockquote></li><ul> <li>Swelling of the optic disk (<span>[[Fig. 25-2|Figure 25-2]]</span>)</li> </ul><li>Headache, projectile vomiting <i>without</i> nausea</li><li>Sinus bradycardia, hypertension</li><li>Potential for herniation (see below)</li> </ol> </ol>
</div></html>
<html><a name="HC025003"></a> <br><a name="P025002"></a><div class="PA" style="color: black; "><ul> <li>Benign intracranial hypertension
<blockquote style="color: blue; ">Intracranial hypertension: papilledema, bradycardia, projectile vomiting, hypertension</blockquote></li><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Increased intracranial pressure</li><ul> <li>Papilledema is present
<blockquote style="color: blue; ">Pseudotumor cerebri: ↑ intracranial pressure <i>without</i> evidence of tumor or obstruction</blockquote></li> </ul><li>Absence of tumor and obstruction to cerebrospinal fluid (CSF) flow</li><li><i>No</i> mental status alterations as one would see with cerebral edema</li><li><i>No</i> focal neurologic signs</li><li>Most commonly seen in obese women of childbearing age
<blockquote style="color: blue; ">Pseudotumor cerebri: most common in young obese women</blockquote></li><li>Other risk factors</li><ul> <li>(1) All-trans-retinoic acid used in treating acute promyelocytic leukemia (refer to <span macro="tag [[12 White Blood Cell Disorders]] [[Chapter 12]]"></span>)</li><li>(2) Hypothyroidism; Cushing disease</li><li>(3) Isotretinoin in treating acne; tamoxifen</li> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Decreased CSF resorption in arachnoid granulations
<blockquote style="color: blue; ">Pseudotumor cerebri: ↓ CSF resorption in arachnoid granulations</blockquote></li><li>Eventual equilibration occurs with inflow and outflow.</li> </ol><li>Clinical findings</li><ol type="a"> <li>Headache</li><li>Rhythmic sound heard in one or both ears
<blockquote style="color: blue; ">Pseudotumor cerebri: headache, blurry vision, diplopia</blockquote></li><li>Diplopia; blurry vision</li> </ol><li>Diagnosis</li><ol type="a"> <li>MRI shows flattening of the posterior globe (100% positive predictive value)</li><li>Increased CSF pressure</li><ul> <li>Usually >300 mm H<sub>2</sub>O (normal, 70-180 mm H<sub>2</sub>O)</li> </ul><li>Decreased CSF protein</li> </ol><li>Treatment</li><ol type="a"> <li>Medical</li><ul> <li>Carbonic anhydrase inhibitor or systemic corticosteroids if visual disturbances (lowers CSF pressure)</li> </ul><li>Surgery</li><ul> <li>(1) Lumboperitoneal shunt</li><li>(2) Optic nerve sheath fenestration (regresses papilledema in the eye)</li> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC025004"></a> <br><a name="P025003"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Cerebral herniation: complication of intracranial hypertension</blockquote>
<ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Complication of increased intracranial pressure</li><li>Portions of the brain become displaced (<span>[[Fig. 25-3|Figure 25-3]]</span>).</li><ul> <li>(1) Openings of dural partitions</li><li>(2) Openings of the skull</li> </ul> </ol><li>Subfalcine herniation
<blockquote style="color: blue; ">Subfalcine herniation: compression of ACA</blockquote></li><ol type="a"> <li>Cingulate gyrus herniates under the falx cerebri.</li><li>Causes compression of the anterior cerebral artery (ACA)</li> </ol><li>Uncal herniation
<blockquote style="color: blue; ">Uncal herniation: compression CN III, PCA, parasympathetic fibers</blockquote></li><ol type="a"> <li>Medial portion of temporal lobe herniates through the tentorium cerebelli.</li><li>Complications</li><ul> <li>(1) Compression of the midbrain</li><ul> <li>Produces Duret's hemorrhages</li> </ul><li>(2) Compression of oculomotor nerve</li><ul> <li>(a) Eye is deviated down and out.
<blockquote style="color: blue; ">Uncal herniation: eye deviated down and out; mydriasis</blockquote></li><li>(b) Pupil is mydriatic (dilated).</li><ul> <li>Compression of parasympathetic postganglionic fibers</li> </ul> </ul><li>(3) Compression of posterior cerebral artery (PCA)</li><ul> <li>Causes hemorrhagic infarction of occipital lobe</li> </ul> </ul> </ol><li>Tonsillar herniation
<blockquote style="color: blue; ">Tonsillar herniation: coning of cerebellar tonsils; cardiorespiratory arrest</blockquote></li><ol type="a"> <li>Cerebellar tonsils herniate into the foramen magnum.</li><li>Causes "coning" of the cerebellar tonsils (<span>[[Fig. 25-4|Figure 25-4]]</span>)</li><li>Produces cardiorespiratory arrest</li> </ol> </ol>
</div></html>
![[25.I.A.Cerebral edema]]
<<tiddler [[25.I.A.Cerebral edema]]>>
![[25.I.B.Pseudotumor cerebri]]
<<tiddler [[25.I.B.Pseudotumor cerebri]]>>
![[25.I.C.Cerebral herniation]]
<<tiddler [[25.I.C.Cerebral herniation]]>>
![[25.I.D.Hydrocephalus]]
<<tiddler [[25.I.D.Hydrocephalus]]>>
<html><a name="HC025005"></a> <br><a name="B025001"></a><div class="BT">BOX 25-1 CEREBROSPINAL FLUID (CSF) ANALYSIS</div><a name="PB025002"></a><div class="BB" style="color: rgb(47, 79, 79); ">CSF derives from the choroid plexus in the ventricles and enters the subarachnoid space. It cushions the brain and spinal cord and transmits chemicals to reach other parts of the brain. CSF is reabsorbed by the arachnoid granulations and drained into dural venous sinuses, which eventually drain into the jugular vein.</div><a name="PB025003"></a><div class="BB" style="color: rgb(47, 79, 79); ">CSF normally is clear and colorless. <b>Turbidity</b> may be caused by an increase in protein, cells, microbial pathogens, or a combination of all three elements. <b>Bloody CSF</b> from spinal taps is most commonly iatrogenic but can also represent a pathologic hemorrhage into the subarachnoid space (e.g., ruptured berry aneurysm, intracerebral bleed near the surface of the brain or ventricles). If the bloody tap is iatrogenic, the supranate should be clear after centrifugation, particularly in the last tube collected in the spinal tap. In pathologic bleeds, there are sequential color changes that occur. CSF colors after centrifugation may be pink- or orange-tinged. A pink color is due to oxyhemoglobin (oxyHb) from ruptured red blood cells. It first occurs 2-4 hours post-bleed, peaks in 24-36 hours, and subsides in 4-8 days. A yellow to orange color (xanthochromia) is due to oxyHb breakdown into bilirubin. It first appears 12 hours post-bleed, peaks in 2-4 days, and subsides in 2-4 weeks. <b>CSF protein</b> normally is 15-45 mg/dL. CSF prealbumin and albumin derive from plasma; therefore, increased levels of these proteins must be due to increased capillary permeability (e.g., acute inflammation). <b>CSF gamma (γ) globulins</b> derive from the synthesis of IgG by plasma cells within the central nervous system (CNS). In a CSF electrophoresis, CSF γ-globulins account for <12% of the total protein. An increase in CSF IgG is due to either increased synthesis of IgG in the CNS (e.g., multiple sclerosis) or an increase in capillary vessel permeability in acute inflammation (e.g., meningitis). It is clinically important to make this distinction. A <b>CSF IgG index</b> (calculated with a formula) is useful in distinguishing acute inflammation from demyelinating diseases, the most common CNS disease producing an increase in IgG. An increase in the CSF IgG index correlates with a CNS origin of the IgG, and a decreased index indicates
acute inflammation. <b>Routine CSF electrophoresis</b> quantitates the amount of γ-globulins that are present when CSF protein is increased. <b>High-resolution CSF electrophoresis</b>, however, is most useful in detecting demyelinating disease, of which multiple sclerosis is the most common cause. Other demyelinating diseases include neurosyphilis and Guillain-Barré syndrome. High-resolution detects <b>oligoclonal bands</b> in the γ-globulin region (see <span>[[Fig. 25-27D|Figure 25-27]]</span>). These are discrete, discontinuous bands originating from single clones of immunocompetent B cells. Another test for demyelinating disease is <b>myelin basic protein (MBP),</b> a protein that is normally present in myelin. An increased CSF MBP occurs with active demyelinating disease. CSF MBP is decreased when a demyelinating disease is in remission.</div><a name="PB025004"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>CSF glucose</b> does <i>not</i> have the same concentration as serum glucose. A normal value for CSF glucose is 50-75 mg/dL, but a normal value in serum glucose is 70-110 mg/dL. A rough estimate of what the CSF glucose should be is to multiply a serum sample value obtained 30-90 minutes <i>before</i> the lumbar puncture by 0.66. For example, if the serum glucose is 100 mg/dL, then the CSF glucose should be around 66 mg/dL. A decreased CSF glucose (hypoglycorrhachia) is defined as a glucose level < 40 mg/dL. It implies that there has been increased uptake of glucose by cellular elements in the CSF (e.g., neutrophils in acute bacterial meningitis, malignant cells) or a defect in the glucose carrier system (frequently occurs in bacterial/fungal meningitis). CSF glucose is usually normal in viral meningitis, neurosyphilis, demyelinating disease, and a cerebral abscess. Exceptions in which viral infections of the CNS produce a decreased CSF glucose include infections associated with mumps, herpes simplex, and the lymphocytic choriomeningitis virus. <b>CSF chloride</b> is usually greater than the serum chloride (limited usefulness). The <b>CSF white blood cell count</b> normally is 0-5 mononuclear cells/mm<sup>3</sup>. Neutrophils are <i>never</i> normal in the CSF. An increased CSF WBC count is most often due to meningitis caused by microbial pathogens. Bacterial meningitis usually has a predominance of neutrophils, while viral meningitis initially has a neutrophil response in the first 24 hours that changes to a predominantly lymphocytic response in 2-3 days. Fungal meningitis is characterized by a predominance of lymphocytes and monocytes. A parasitic meningitis usually has a mixed inflammatory infiltrate (eosinophils suggest a helminth infection). A <b>Gram stain</b> is useful for detecting bacteria (75-80% sensitivity) in the sediment after ultracentrifugation of the CSF. Other tests include culture, India ink for <i>Cryptococcus neoformans</i> (sensitivity is 50%), antigen detection (sensitivity depends on the pathogen; specificity is 96-100%), enzyme immunoassay (96-100% sensitivity/specificity), and polymerase chain reaction studies that detect DNA (sensitivity 94%, specificity 96%).</div><a name="P025004"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Hydrocephalus: enlargement of ventricles</blockquote>
<ul> <li>Increase in the CSF volume causes enlargement of the ventricles.</li><ol type="1"> <li>Production and movement of CSF</li><ol type="a"> <li>Produced by the choroid plexus in the ventricles
<blockquote style="color: blue; ">CSF: produced by choroid plexus; reabsorbed by arachnoid granulations</blockquote></li><li>Exits fourth ventricle through foramina and enters subarachnoid space</li><li>Reabsorbed by the arachnoid granulations into the dural venous sinuses</li><li>CSF analysis (<span>[[Box 25-1|BOX 25-1 CEREBROSPINAL FLUID (CSF) ANALYSIS]]</span>)</li> </ol><li>Communicating (nonobstructive) hydrocephalus</li><ol type="a"> <li>Open communication between ventricles and subarachnoid space</li><li>Causes
<blockquote style="color: blue; ">Communicating hydrocephalus: ↑ production CSF; ↓ reabsorption CSF</blockquote></li><ul> <li>(1) Increased CSF production</li><ul> <li>Example-choroid plexus papilloma</li> </ul><li>(2) Obstruction in reabsorption of CSF by arachnoid granulations</li><ul> <li>Examples-postmeningitic scarring, tumor</li> </ul> </ul> </ol><li>Noncommunicating (obstructive) hydrocephalus
<blockquote style="color: blue; ">Noncommunicating hydrocephalus: obstruction CSF outflow into ventricles</blockquote></li><ol type="a"> <li>Obstruction of CSF flow out of the ventricles</li><li>Causes</li><ul> <li>(1) Stricture of the aqueduct of Sylvius</li><ul> <li>(a) Most common cause in newborns
<blockquote style="color: blue; ">Blockage aqueduct of Sylvius: most common cause of hydrocephalus in newborns</blockquote></li><li>(b) Paralysis of upward gaze (Parinaud's syndrome; <span>[[Fig. 25-5|Figure 25-5]]</span>)</li> </ul><li>(2) Tumor in the fourth ventricle</li><ul> <li>Examples-ependymoma, medulloblastoma</li> </ul><li>(3) Scarring at the base of the brain</li><ul> <li>Example-tuberculous meningitis</li> </ul><li>(4) Colloid cyst in the third ventricle</li><li>(5) Developmental disorders (see section II)</li> </ul> </ol><li>Clinical findings
<blockquote style="color: blue; ">Hydrocephalus children: ventricles dilate and enlarge head circumference</blockquote></li><ol type="a"> <li>Newborns</li><ul> <li>Ventricles dilate and enlarge the head circumference (see <span>[[Fig. 25-5|Figure 25-5]]</span>).</li> </ul><li>Adults
<blockquote style="color: blue; ">Hydrocephalus adults: no increase in head size; dementia, gait disturbance, urinary incontinence</blockquote></li><ul> <li>Ventricles enlarged but <i>no</i> increase in head circumference</li> </ul> </ol><li>Hydrocephalus ex vacuo</li><ol type="a"> <li>Dilated appearance of the ventricles when the brain mass is decreased</li><li>Example-Alzheimer's disease</li> </ol><li>Normal pressure hydrocephalus
<blockquote style="color: blue; ">Hydrocephalus ex vacuo: dilated ventricles secondary to brain atrophy</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Dilated ventricles + symptom complex of:</li><ul> <li>(a) Wide-based gait</li><li>(b) Urinary incontinence</li><li>(c) Dementia</li> </ul><li>(2) Dilated ventricles but normal CSF pressure
<blockquote style="color: blue; ">Normal pressure hydrocephalus: dilated ventricles + triad-dementia, urinary incontinence, wide-based gait</blockquote></li><li>(3) Accounts for 5% of dementia cases</li><li>(4) Potentially reversible cause of dementia</li> </ul><li>Causes</li><ul> <li>(1) Idiopathic (50%)</li><li>(2) Secondary causes
<blockquote style="color: blue; ">Normal pressure hydrocephalus: potentially reversible cause of dementia with shunting</blockquote></li><ul> <li>(a) Prior subarachnoid hemorrhage</li><li>(b) Prior intracranial surgery</li><li>(c) Prior trauma</li> </ul> </ul><li>Pathogenesis</li><ul> <li>(1) Increased subarachnoid space volume</li><li>(2) Ventricular dilation is out of proportion to sulcal atrophy ("ventriculomegaly")</li><li>(3) Wide-based gait and urinary incontinence due to stretching of sacral motor fibers near the dilated ventricle
<blockquote style="color: blue; ">Wide-based gait/urinary incontinence: stretching of sacral motor fibers</blockquote></li><li>(4) Dementia due to stretching of limbic fibers near the dilated ventricle
<blockquote style="color: blue; ">Dementia: stretching of the limbic fibers</blockquote></li> </ul><li>Diagnosis</li><ul> <li>(1) MRI documents ventriculomegaly and sulcal atrophy.</li><li>(2) Large volume of CSF is removed at lumbar puncture.</li><ul> <li>Symptoms improve with removal of the fluid.</li> </ul> </ul><li>Treatment</li><ul> <li>Ventriculoperitoneal or ventriculoatrial shunting</li> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC025007"></a> <br><a name="P025011"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Neural tube defects: failure of fusion of lateral folds of neural plate; ↑ AFP</blockquote>
<ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Failure of fusion of the lateral folds of the neural plate</li><li>Rupture of a previously closed neural tube</li> </ol><li>Maternal findings
<blockquote style="color: blue; ">Maternal folate level must be adequate <i>before</i> pregnancy</blockquote></li><ul> <li>Increased maternal α-fetoprotein (AFP) in serum or amniotic fluid</li> </ul><li>Anencephaly
<blockquote style="color: blue; ">Anencephaly: absence of brain; maternal polyhydramnios</blockquote></li><ol type="a"> <li>Complete absence of brain (<span>[[Fig. 25-6|Figure 25-6]]</span>)</li><li>Frog-like appearance</li><li>Maternal polyhydramnios</li> </ol><li>Spina bifida occulta (<span>[[Fig. 25-7A|Figure 25-7]]</span>)
<blockquote style="color: blue; ">Spina bifida occulta: dimple/tuft of hair overlying L5-S1</blockquote></li><ol type="a"> <li>Defect in closure of the posterior vertebral arch</li><li>Dimple or tuft of hair in the skin overlying L5-S1</li> </ol><li>Meningocele (<span>[[Fig. 25-7B|Figure 25-7]]</span>)
<blockquote style="color: blue; ">Meningocele: cystic mass with meninges</blockquote></li><ol type="a"> <li>Spina bifida with cystic mass containing meninges</li><li>Most common in lumbosacral region</li> </ol><li>Meningomyelocele (<span>[[Fig. 25-7C|Figure 25-7]]</span>)
<blockquote style="color: blue; ">Meningomyelocele: cystic mass with meninges and spinal cord</blockquote></li><ol type="a"> <li>Spina bifida with cystic mass containing meninges and spinal cord</li><li>Most common in lumbosacral region</li> </ol> </ol>
</div></html>
<html><a name="HC025008"></a> <br><a name="P025012"></a><div class="PA" style="color: black; "><ol type="1"> <li>Caudal extension of medulla and cerebellar vermis through foramen magnum
<blockquote style="color: blue; ">Arnold-Chiari: caudal extension medulla/cerebellar vermis through foramen; hydrocephalus; meningomyelocele; syringomyelia</blockquote></li><li>Noncommunicating hydrocephalus</li><li>Platybasia (flattening of base of skull)</li><li>Associations:</li><ol type="a"> <li>Meningomyelocele</li><li>Syringomyelia</li> </ol><li>Treatment</li><ul> <li>Decompression surgery</li> </ul> </ol>
</div></html>
<html><a name="HC025009"></a> <br><a name="P025013"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Dandy-Walker: partial/complete absence of cerebellar vermis; cystic dilation of 4th ventricle; hydrocephalus</blockquote>
<ol type="1"> <li>Partial or complete absence of the cerebellar vermis</li><li>Cystic dilation of fourth ventricle</li><li>Noncommunicating hydrocephalus</li><li>Treatment</li><ul> <li>Shunt to treat hydrocephalus</li> </ul> </ol>
</div></html>
<html><a name="HC025010"></a> <br><a name="P025014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Degenerative disease of spinal cord
<blockquote style="color: blue; ">Syringomyelia: degenerative disease of spinal cord; usually cervical cord</blockquote></li><ol type="a"> <li>Symptoms appear in the third and fourth decades.</li><li>Fluid-filled cavity (syrinx) within the cervical spinal cord (<span>[[Fig. 25-8|Figure 25-8]]</span>)</li><li>Produces cervical cord enlargement</li><li>Cavity expands and causes degeneration of spinal tracts.
<blockquote style="color: blue; ">Syringomyelia: cervical cord enlargment; fluid-filled cavity</blockquote></li> </ol><li>Associated with Arnold-Chiari malformation</li><li>Pathogenesis</li><ol type="a"> <li>Obstruction of outflow from fourth ventricle</li><li>Birth injury</li> </ol><li>Clinical findings
<blockquote style="color: blue; ">Syringomyelia: ↓ pain/temperature sensation in hands; loss intrinsic muscles of hand</blockquote></li><ol type="a"> <li>Disruption of the crossed lateral spinothalamic tracts</li><ul> <li>(1) Loss of pain and temperature sensation in the hands</li><ul> <li>Tactile sense preserved</li> </ul><li>(2) Patient can burn hands <i>without</i> being aware of the burn.</li> </ul><li>Destruction of anterior horn cells</li><ul> <li>(1) Atrophy of intrinsic muscles of the hands</li><li>(2) Often confused with amyotrophic lateral sclerosis (ALS)</li><ul> <li><i>No</i> sensory changes in ALS</li> </ul> </ul><li>Charcot joint shoulder, elbow, wrist</li> </ol><li>Diagnosis
<blockquote style="color: blue; ">Syringomyelia: MRI shows cervical enlargement and cavity</blockquote></li><ul> <li>MRI shows enlarged cervical cord and cystic cavity.</li> </ul><li>Treatment</li><ul> <li>Drainage of syrinx slows progression.</li> </ul> </ol>
</div></html>
![[25.II.A.Neural tube defects]]
<<tiddler [[25.II.A.Neural tube defects]]>>
![[25.II.B.Arnold-Chiari malformation]]
<<tiddler [[25.II.B.Arnold-Chiari malformation]]>>
![[25.II.C.Dandy-Walker malformation]]
<<tiddler [[25.II.C.Dandy-Walker malformation]]>>
![[25.II.D.Syringomyelia]]
<<tiddler [[25.II.D.Syringomyelia]]>>
![[25.II.E.Phakomatoses (neurocutaneous syndromes)]]
<<tiddler [[25.II.E.Phakomatoses (neurocutaneous syndromes)]]>>
<html><a name="HC025011"></a> <br><a name="P025015"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Phakomatosis: neurocutaneous syndromes</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Neurocutaneous syndromes</li><li>Disordered growth of ectodermal tissue</li><li>Malformations or tumors of the CNS</li><li>Includes the following in descending order of incidence:</li><ul> <li>Neurofibromatosis, tuberous sclerosis, Sturge-Weber syndrome</li> </ul> </ol><li>Neurofibromatosis (NF)</li><ol type="a"> <li>Autosomal dominant (AD) disorder with incomplete penetrance
<blockquote style="color: blue; ">NF: AD; incomplete penetrance</blockquote></li><li>No gender predominance</li><li>Type 1 (NF1; most common) and type 2 (NF2) variants</li><ul> <li>(1) NF1-mutation on chromosome 17 coding for neurofibromin</li><li>(2) NF2-mutation on chromosome 22 coding for merlin</li><li>(3) Both proteins act as tumor suppressors.</li> </ul><li>NF1 (peripheral type) associated with:</li><ul> <li>(1) Café au lait coffee-colored macules (<span>[[Fig. 25-9|Figure 25-9]]</span>)
<blockquote style="color: blue; ">Both types: café au lait macules; neurofibromas</blockquote></li><ul> <li>(a) Occur in both types</li><li>(b) Occur in 100% of children <i>before</i> 2 years of age</li> </ul><li>(2) Optic gliomas (2-5%); astrocytomas
<blockquote style="color: blue; ">NF1: optic gliomas; Lisch nodules; axillary/inguinal freckling</blockquote></li><li>(3) Lisch nodules (>90%)</li><ul> <li>Hamartoma of the iris</li> </ul><li>(4) Axillary and inguinal freckling (70%)</li><li>(5) Mild scoliosis</li><li>(6) Pigmented plexiform neurofibromas (<i>not</i> in NF2)</li><ul> <li>May progress into neurofibrosarcoma involving large nerves</li> </ul><li>(7) Pigmented cutaneous/subcutaneous neurofibromas</li><ul> <li>(a) Occur in both types</li><li>(b) Occur anywhere on the body except palms, soles</li><li>(c) Appear in late adolescence and increase in size with age</li><li>(d) Focal or diffuse
<blockquote style="color: blue; ">NF1 tumor associations: pheochromocytoma; Wilms' tumor; CML (juvenile)</blockquote></li> </ul><li>(8) Tumor associations</li><ul> <li>(a) Pheochromocytoma; Wilms' tumor</li><ul> <li>Both produce hypertension.</li> </ul><li>(b) Juvenile chronic myelogenous leukemia (CML)</li> </ul><li>(9) Neurodevelopment problems (30-40%)</li> </ul><li>NF2 (central type); associated with:
<blockquote style="color: blue; ">NF2: bilateral acoustic neuromas; juvenile cataracts; meningiomas</blockquote></li><ul> <li>(1) Bilateral acoustic neuromas (schwannoma; >90%)</li><ul> <li>(a) Cranial nerve (CN) VIII tumor</li><li>(b) Benign tumor</li><li>(c) Sensorineural hearing loss; tinnitus</li> </ul><li>(2) Meningiomas</li><li>(3) Spinal schwannomas</li><li>(4) Juvenile cataracts (∼80%)</li> </ul><li>Genetic testing available for both types</li><li>Treatment is mainly surgical.</li> </ol><li>Tuberous sclerosis</li><ol type="a"> <li>AD disorder</li><li>Second most common phakomatosis after neurofibromatosis</li><li>Mental retardation and seizures (infantile spasms) beginning in infancy
<blockquote style="color: blue; ">Tuberous sclerosis: AD; mental retardation; hamartomas in brain, kidneys</blockquote></li><li>Angiofibromas (adenoma sebaceum) on the face (<span>[[Fig. 25-10|Figure 25-10]]</span>)</li><li>Hypopigmented skin lesions ("ash leaf" lesions; <span>[[Fig. 25-11|Figure 25-11]]</span>)</li><ul> <li>(1) Best identified with Wood's lamp</li><li>(2) Occur in >80% of cases
<blockquote style="color: blue; ">Triad: seizures, mental retardation, angiofibromas, ash leaf lesions</blockquote></li> </ul><li>Hamartomatous lesions</li><ul> <li>(1) Astrocyte proliferations in subependyma</li><ul> <li>Look like "candlestick drippings" in the ventricles</li> </ul><li>(2) Angiomyolipomas in the kidneys (80%)</li> </ul><li>Rhabdomyoma in the heart (50-60%)
<blockquote style="color: blue; ">Rhabdomyoma of heart: highly predictive of tuberous sclerosis</blockquote></li><ul> <li>Almost 100% predictive of tuberous sclerosis</li> </ul> </ol><li>Sturge-Weber syndrome (SWS; refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>; see <span>[[Fig. 9-9D|Figure 9-9]]</span>)
<blockquote style="color: blue; ">SWS: vascular malformation of face; ipsilateral arteriovenous malformation in meninges in some patients</blockquote></li><ol type="a"> <li>Somatic mosaicism or sporadic</li><li>Vascular malformation on the face</li><ul> <li>In a trigeminal nerve distribution</li> </ul><li>Some patients have ipsilateral arteriovenous malformation in the meninges.</li> </ol> </ol>
</div></html>
<html><a name="HC025013"></a> <br><a name="P025019"></a><div class="PA" style="color: black; "><ol type="1"> <li>Permanent damage to small blood vessels and the surface of the brain</li><li>Most often secondary to an acceleration-deceleration injury</li><li>Coup injuries occur at the <i>site</i> of impact (<span>[[Fig. 25-12|Figure 25-12]]</span>).
<blockquote style="color: blue; ">Coup injuries: site of impact</blockquote></li><li>Contrecoup injuries occur <i>opposite</i> the site of impact.
<blockquote style="color: blue; ">Contrecoup injuries: opposite site of impact</blockquote></li><ul> <li>Common sites are at the tips of the frontal and temporal lobes.</li> </ul> </ol>
</div></html>
<html><a name="HC025014"></a> <br><a name="P025020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Occurs in 1% to 2% of head injuries</li><li>Arterial bleed creates a blood-filled space between the bone and dura (<span>[[Fig. 25-13A and B|Figure 25-13]]</span>).</li><li>Caused by a fracture of the temporoparietal bone
<blockquote style="color: blue; ">Epidural hematoma: temporoparietal skull fracture; tear of middle meningeal artery</blockquote></li><ul> <li>(1) Causes-hammer; baseball bat; any focused blow to head</li><li>(2) Severance of the middle meningeal artery</li><li>(3) Vessel lies between the dura and inner table of bone.</li> </ul> </ol><li>Some patients have lucid interval after trauma followed later by neurologic deterioration.</li><li>Intracranial pressure increases, leading to herniation and death.</li><li>Diagnosis</li><ol type="a"> <li>Head CT scan is the imaging test of choice.
<blockquote style="color: blue; ">CT scan: imaging test of choice</blockquote></li><li>Hematoma rarely crosses the suture line due to firm attachment of dura at these sites.</li> </ol><li>Treatment consists of creating burr holes to relieve pressure.</li> </ol>
</div></html>
<html><a name="HC025015"></a> <br><a name="P025021"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Subdural hematoma: venous bleed between dura and arachnoid membranes</blockquote>
<ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Venous bleeding between the dura and arachnoid membranes</li><li>Causes</li><ul> <li>(1) Most often the result of blunt trauma</li><ul> <li>Examples-car accident, baseball bat
<blockquote style="color: blue; ">Subdural hematoma: most often caused by trauma; increased risk with cerebral atrophy</blockquote></li> </ul><li>(2) Other causes</li><ul> <li>(a) Medical anticoagulation</li><li>(b) Hemophilia</li><li>(c) Child abuse; shaken baby syndrome</li><li>(d) Spontaneous</li> </ul><li>(3) Risk factors</li><ul> <li>(a) Elderly patients and alcoholic with atrophy of brain</li><li>(b) Loss of brain mass leads to excess traction on the inflexible bridging veins</li> </ul> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Tearing of bridging veins between brain and dural sinuses (<span>[[Fig. 25-13C and D|Figure 25-13]]</span>)
<blockquote style="color: blue; ">Subdural hematoma: tear of bridging veins producing venous blood clot</blockquote></li><li>Slowly enlarging blood clot covers the convexity of the brain.</li> </ol><li>Clinical findings</li><ol type="a"> <li>Fluctuating levels of consciousness</li><li>Herniation and death may occur.</li><li>Chronic subdural hematomas may produce dementia.</li> </ol><li>CT scan is best imaging study
<blockquote style="color: blue; ">CT scan: imaging test of choice</blockquote></li><li>Treatment consists of creating burr holes to relieve pressure.</li> </ol>
</div></html>
![[25.III.A.Cerebral contusion]]
<<tiddler [[25.III.A.Cerebral contusion]]>>
![[25.III.B.Acute epidural hematoma]]
<<tiddler [[25.III.B.Acute epidural hematoma]]>>
![[25.III.C.Subdural hematoma]]
<<tiddler [[25.III.C.Subdural hematoma]]>>
<html><a name="HC025017"></a> <br><a name="PB025005"></a><div class="BB" style="color: rgb(47, 79, 79); ">Repeated episodes of <b>hypoglycemia</b> have the same effects on the brain as does global hypoxic injury. Hypoglycemia most commonly occurs in type 1 diabetes mellitus.</div><a name="P025026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes of global hypoxic injury (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li><ol type="a"> <li>Cardiac arrest</li><li>Hypovolemic shock; septic shock</li><li>Chronic carbon monoxide (CO) poisoning
<blockquote style="color: blue; ">Global hypoxic injury: hypotensive episodes; chronic CO poisoning</blockquote></li> </ol><li>Complications
<blockquote style="color: blue; ">Complications: cerebral atrophy; watershed infarcts; stroke</blockquote></li><ol type="a"> <li>Cerebral atrophy (see <span>[[Fig. 1-10A|Figure 1-10]]</span>)</li><ul> <li>(1) Due to apoptosis of neurons in layers 3, 5, and 6 of the cerebral cortex</li><ul> <li>Produces laminar necrosis</li> </ul><li>(2) Neurons are the most susceptible cell to hypoxic injury.</li><li>(3) Neurons undergo apoptosis ("red" neurons; <span>[[Fig. 25-14|Figure 25-14]]</span>).
<blockquote style="color: blue; ">Red neurons: apoptotic neuron</blockquote></li> </ul><li>Watershed infarcts (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>; see <span>[[Fig. 1-4|Figure 1-4]]</span>)</li><ul> <li>(1) Occur at the junctions of arterial territories
<blockquote style="color: blue; ">Hypoglycemia: ∼effect on brain as global hypoxia</blockquote></li><li>(2) Example-junction between the anterior and middle cerebral arteries</li> </ul><li>Cerebrovascular accident (e.g., stroke)</li> </ol> </ol>
</div></html>
<html><a name="HC025018"></a> <br><a name="P025027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Increased incidence with age
<blockquote style="color: blue; ">Strokes: ↑ incidence with age</blockquote></li><li>Peak incidence is between 80 and 84 years of age.</li><li>More common in men than women</li><li>Types of strokes</li><ul> <li>(1) Ischemic (70-80%)</li><ul> <li>(a) Atherosclerotic</li><ul> <li>Most common type</li> </ul><li>(b) Embolic</li> </ul><li>(2) Intracerebral hemorrhage</li><li>(3) Subarachnoid hemorrhage</li><li>(4) Lacunar stroke</li> </ul> </ol><li>Atherosclerotic (thrombotic) stroke</li><ol type="a"> <li>Most common overall type of stroke
<blockquote style="color: blue; ">Atherosclerotic stroke: most common overall stroke; ischemic type of stroke</blockquote></li><ul> <li>Ischemic type of stroke due to thrombosis</li> </ul><li>Usually pale infarcts (liquefactive necrosis)</li><ul> <li>(1) Platelet thrombus develops over a disrupted plaque. Sites:
<blockquote style="color: blue; ">Atherosclerotic stroke: pale infarction extending to periphery of cerebral cortex</blockquote></li><ul> <li>(a) Middle cerebral artery (MCA)</li><li>(b) Internal carotid artery near the bifurcation</li> </ul><li>(2) Reperfusion does <i>not</i> usually occur.</li><ul> <li>Hemorrhagic infarction develops if reperfusion occurs.</li> </ul> </ul><li>Most occur in the distribution of the MCA.
<blockquote style="color: blue; ">Atherosclerotic stroke: most occur in MCA distribution</blockquote></li><li>Gross and microscopic findings</li><ul> <li>(1) Wedge-shaped area of pale infarction</li><ul> <li>Develops at the <i>periphery</i> of the cerebral cortex (<span>[[Fig. 25-15|Figure 25-15]]</span>)</li> </ul><li>(2) Swelling of the brain occurs.</li><ul> <li>(a) Loss of demarcation between gray and white mater</li><li>(b) Myelin begins to break down.</li> </ul><li>(3) Gliosis is the reaction to injury.
<blockquote style="color: blue; ">Atherosclerotic stroke: infarction with liquefactive (<i>not</i> coagulative) necrosis</blockquote></li><ul> <li>(a) Astrocytes proliferate at the margins of the infarct.</li><li>(b) Microglial cells (macrophages) remove lipid debris.</li> </ul><li>(4) Cystic area develops after 10 days to 3 weeks.</li><ul> <li>Example of liquefactive necrosis</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Most atherosclerotic strokes are preceded by transient ischemic attacks (TIAs).
<blockquote style="color: blue; ">TIA: transient neurologic deficit lasting <24 hours; microembolization of plaque material</blockquote></li><ul> <li>(a) Transient neurologic deficits last <24 hours.</li><ul> <li>Visual loss, paresthesias, hemiparesis, loss of speech</li> </ul><li>(b) Usually caused by microembolization of plaque material</li> </ul><li>(2) Deficits that do <i>not</i> resolve within 24 hours are called strokes.</li><li>(3) Amaurosis fugax</li><ul> <li>Temporary loss of vision due to embolization of atherosclerotic material to bifurcation of retinal arteries; called Hollenhorst plaque (<span>[[Fig. 25-16|Figure 25-16]]</span>)</li> </ul><li>(4) Treatment of TIA</li><ul> <li>Aspirin; clopidogrel; ticlopidine
<blockquote style="color: blue; ">Amaurosis fugax: temporary loss of vision; embolic material trapped at bifurcation of retinal vessels</blockquote></li> </ul><li>(5) Strokes involving the MCA</li><ul> <li>(a) Contralateral hemiparesis and sensory loss in the face and upper extremity</li><li>(b) Expressive aphasia</li><ul> <li>If Broca's area is involved in the dominant (left) hemisphere</li> </ul><li>(c) Visual field defects</li><li>(d) Head and eyes deviate <i>toward</i> the side of the lesion.
<blockquote style="color: blue; ">MCA stroke: contralateral paresis/sensory loss in face/upper extremity; head/eyes deviate to side of lesion</blockquote></li> </ul><li>(6) Strokes involving anterior cerebral artery (ACA)</li><ul> <li>Contralateral hemiparesis and sensory loss in the lower extremity</li><li>ACA stroke: contralateral paresis/sensory loss in lower extremity
<blockquote style="color: blue; ">ACA stroke: contralateral paresis/sensory loss in lower extremity</blockquote></li> </ul><li>(7) Strokes involving vertebrobasilar arterial system</li><ul> <li>(a) Vertigo, ataxia</li><li>(b) Ipsilateral sensory loss in face</li><li>(c) Contralateral hemiparesis and sensory loss in the trunk and limbs</li> </ul> </ul><li>Prevention of atherosclerotic strokes</li><ul> <li>Aspirin; clopidogrel if allergic to aspirin</li> </ul> </ol><li>Embolic (hemorrhagic) stroke
<blockquote style="color: blue; ">Embolic stroke: ischemic type of stroke due to embolization</blockquote></li><ol type="a"> <li>Ischemic type of stroke due to embolization</li><li>Source of emboli</li><ul> <li>Most often originate from the left side of the heart (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>)</li> </ul><li>Produces a hemorrhagic infarction
<blockquote style="color: blue; ">Embolic stroke: hemorrhagic infarction extending to periphery of cerebral cortex</blockquote></li><ul> <li>(1) Most occur in the distribution of the MCA (<span>[[Fig. 25-17|Figure 25-17]]</span>).</li><li>(2) Vessel reperfusion after lysis of embolic material produces hemorrhage.</li> </ul> </ol><li>Intracerebral hemorrhage
<blockquote style="color: blue; ">Intracerebral hemorrhage: complication of hypertension; rupture of aneurysm</blockquote></li><ol type="a"> <li>Most often due to stress imposed on vessels by hypertension</li><ul> <li>(1) Branches of lenticulostriate vessels develop Charcot-Bouchard macroaneurysms.</li><li>(2) Rupture of aneurysms produces intracerebral hemorrhage (hematoma).
<blockquote style="color: blue; ">Rx hypertension reduces the incidence of stroke by more than 40%.</blockquote></li><ul> <li>Intracerebral hematoma pushes the brain parenchyma aside (<span>[[Fig. 25-18|Figure 25-18]]</span>).
<blockquote style="color: blue; ">Intracerebral hemorrhage: basal ganglia most common location</blockquote></li> </ul> </ul><li>Common sites of hemorrhage</li><ul> <li>(1) Basal ganglia (35-50% occur in the putamen)</li><li>(2) Thalamus (10%)</li><li>(3) Pons and cerebellar hemispheres (10%)</li> </ul> </ol><li>Subarachnoid hemorrhage</li><ol type="a"> <li>Causes</li><ul> <li>(1) Majority are secondary to rupture of a congenital berry aneurysm.
<blockquote style="color: blue; ">Subarachnoid hemorrhage: rupture of congenital berry aneurysm</blockquote></li><li>(2) Bleeding from an arteriovenous malformation is a less common cause.</li> </ul><li>Congenital berry aneurysm</li><ul> <li>(1) May develop from normal hemodynamic stress or hypertension</li><li>(2) Most develop at junctions of communicating branches with main cerebral artery (<span>[[Fig. 25-19|Figure 25-19]]</span>).</li><ul> <li>(a) Junction lacks internal elastic lamina and smooth muscle.
<blockquote style="color: blue; ">Berry aneurysms: junction of communicating branch with main cerebral artery</blockquote></li><li>(b) Most common site for berry aneurysm is junction with ACA.</li> </ul><li>(3) Rupture releases blood into the subarachnoid space.</li><ul> <li>Blood covers the surface of the brain (<span>[[Fig. 25-20|Figure 25-20]]</span>).</li> </ul><li>(4) Blood in the CSF is broken down into bilirubin pigment.</li><ul> <li>Imparts a yellow color to CSF called xanthochromia (see <span>[[Box 25-1|BOX 25-1 CEREBROSPINAL FLUID (CSF) ANALYSIS]]</span>)</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Sudden onset of severe occipital headache
<blockquote style="color: blue; ">Subarachnoid hemorrhage: severe occipital headache; described as "worst headache ever"</blockquote></li><ul> <li>(a) Described as "worst headache ever"</li><li>(b) Nuchal rigidity is present.</li> </ul><li>(2) About 50% of patients die soon after the hemorrhage.</li><li>(3) Complications</li><ul> <li>(a) Further hemorrhage</li><li>(b) Hydrocephalus</li><ul> <li>Blockage of arachnoid granulations; block foramina</li> </ul><li>(c) Permanent neurologic deficits</li> </ul> </ul> </ol><li>Lacunar infarcts
<blockquote style="color: blue; ">Lacunar strokes: microinfarction < 1 cm</blockquote></li><ol type="a"> <li>Cystic areas of microinfarction < 1 cm in diameter (<span>[[Fig. 25-21|Figure 25-21]]</span>)</li><li>Caused by hyaline arteriolosclerosis
<blockquote style="color: blue; ">Lacunar strokes: hyaline arteriolosclerosis due to hypertension/diabetes</blockquote></li><ul> <li>Secondary to either hypertension (most common) or diabetes mellitus</li> </ul><li>Stroke syndromes</li><ul> <li>(1) Pure motor strokes with or without dysarthria</li><ul> <li>Occur if the posterior limb of the internal capsule is involved</li> </ul><li>(2) Pure sensory strokes</li><ul> <li>Occur if the thalamus is involved</li> </ul> </ul> </ol><li>Diagnosis</li><ol type="a"> <li>CT scan without contrast
<blockquote style="color: blue; ">Diagnosis of strokes: CT without contrast best test</blockquote></li><ul> <li>(1) Overall best imaging technique</li><li>(2) Distinguishes hemorrhage from nonhemorrhagic strokes</li> </ul><li>MRI is most useful for identification of posterior fossa infarcts.</li> </ol><li>Treatment</li><ol type="a"> <li>Acute treatment</li><ul> <li>(1) Depends on the type of stroke and elapsed time to arrival at a hospital</li><li>(2) Thrombolytic therapy in thromboembolic strokes</li><ul> <li>(a) Depends on the time interval of symptoms (<3 hours is ideal)</li><li>(b) Usually <i>not</i> implemented if stroke is hemorrhagic</li> </ul><li>(3) In some cases, intracerebral hemorrhages can be evacuated.</li> </ul><li>Chronic treatment</li><ul> <li>(1) Antiplatelet treatment (e.g., aspirin, clopidogrel)</li><li>(2) Warfarin for embolic types of strokes</li><li>(3) Treat risk factors for strokes (e.g., hypertension, diabetes)</li> </ul> </ol> </ol>
</div></html>
![[25.IV.A.Global hypoxic injury]]
<<tiddler [[25.IV.A.Global hypoxic injury]]>>
![[25.IV.B.Strokes]]
<<tiddler [[25.IV.B.Strokes]]>>
<html><a name="HC025044"></a> <br><a name="P025069"></a><div class="PA" style="color: black; "><ol type="1"> <li>Primary brain tumors in adults</li><ol type="a"> <li>Approximately 70% occur above the tentorium cerebelli.</li><li>In order of decreasing frequency:
<blockquote style="color: blue; ">Most common primary CNS tumor in adults: glioblastoma multiforme</blockquote></li><ul> <li>Glioblastoma multiforme, meningioma, ependymoma</li> </ul> </ol><li>Primary brain tumors in children</li><ol type="a"> <li>Second most common cancer in children</li><li>Approximately 70% occur <i>below</i> the tentorium cerebelli.</li><li>In order of decreasing frequency:
<blockquote style="color: blue; ">Childhood tumors: cystic astrocytoma and medulloblastoma, both in cerebellum</blockquote></li><ul> <li>Cystic cerebellar astrocytoma, medulloblastoma, brainstem glioma</li> </ul> </ol><li>Risk factors</li><ul> <li>Turcot's syndrome, neurofibromatosis, cigarette smoking</li> </ul><li>General clinical findings</li><ol type="a"> <li>Headache (20% initially, 60% later)
<blockquote style="color: blue; ">Clinical: headache, seizures, intracranial hypertension</blockquote></li><ul> <li>(1) Tend to be worse during the night; wakes person up</li><li>(2) Accompanied by nausea and vomiting</li> </ul><li>Seizures (>30%)</li><li>Symptoms/signs of intracranial hypertension (see section I)</li> </ol><li>Imaging studies</li><ol type="a"> <li>MRI with gadolinium enhancement</li><li>CT scan useful if calcium or hemorrhage is present</li><li>Functional MRI for lesions in vital areas</li><li>PET</li> </ol><li>Treatment modalities</li><ul> <li>Surgery, irradiation, chemotherapy</li> </ul> </ol>
</div></html>
<html><a name="HC025045"></a> <br><a name="P025070"></a><div class="PA" style="color: black; "><ol type="1"> <li>Accounts for about 70% of all neuroglial tumors</li><ol type="a"> <li>Usually involves frontal lobe in adults
<blockquote style="color: blue; ">Astrocytoma: most common neuroglial tumor</blockquote></li><li>Usually involves the cerebellum in children</li><li>Grades I and II are low-grade cancers.</li><li>Grades III and IV are high-grade cancers.</li> </ol><li>Glioblastoma multiforme (GBM)</li><ol type="a"> <li>High-grade astrocytoma</li><ul> <li>(1) May arise de novo</li><li>(2) May arise from dedifferentiation of a low-grade astrocytoma</li> </ul><li>Hemorrhagic tumor (<span>[[Fig. 25-35A|Figure 25-35]]</span>)
<blockquote style="color: blue; ">GBM: grade IV astrocytoma; often crosses corpus callosum; hemorrhagic/cystic</blockquote></li><ul> <li>(1) Multifocal areas of necrosis and cystic degeneration</li><li>(2) Commonly cross the corpus callosum</li> </ul><li>May seed the neuraxis via the CSF</li><ul> <li>Rarely metastasize outside the CNS</li> </ul><li>Generally poor prognosis</li> </ol> </ol>
</div></html>
<html><a name="HC025046"></a> <br><a name="P025071"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most common benign brain tumor in adults
<blockquote style="color: blue; ">Meningioma: most common benign brain tumor in adults</blockquote></li><ul> <li>Female predominance (tumors have estrogen receptors)</li> </ul><li>Derived from arachnoidal cells</li><ul> <li>Locations-parasagittal location, olfactory groove, lesser wing of sphenoid</li> </ul><li>Associated with neurofibromatosis, history of radiation</li><li>Gross and microscopic findings (<span>[[Fig. 25-35B and C|Figure 25-35]]</span>)
<blockquote style="color: blue; ">Meningioma: female predominance; psammoma bodies</blockquote></li><ol type="a"> <li>Firm tumors</li><ul> <li>(1) May indent <i>(not invade)</i> the surface of brain</li><li>(2) Often infiltrate overlying bone</li><ul> <li>Causes increased bone density</li> </ul> </ul><li>Swirling masses of meningothelial cells encompass psammoma bodies (calcified bodies).</li> </ol><li>Common cause of new-onset focal seizures
<blockquote style="color: blue; ">Ependymoma: fourth ventricle in children; cauda equina in adults</blockquote></li> </ol>
</div></html>
![[25.IX.A.Epidemiology]]
<<tiddler [[25.IX.A.Epidemiology]]>>
![[25.IX.B.Astrocytoma]]
<<tiddler [[25.IX.B.Astrocytoma]]>>
![[25.IX.C.Meningioma]]
<<tiddler [[25.IX.C.Meningioma]]>>
![[25.IX.D.Ependymoma]]
<<tiddler [[25.IX.D.Ependymoma]]>>
![[25.IX.E.Medulloblastoma]]
<<tiddler [[25.IX.E.Medulloblastoma]]>>
![[25.IX.F.Oligodendroglioma]]
<<tiddler [[25.IX.F.Oligodendroglioma]]>>
![[25.IX.G.CNS lymphoma]]
<<tiddler [[25.IX.G.CNS lymphoma]]>>
![[25.IX.H.Metastasis]]
<<tiddler [[25.IX.H.Metastasis]]>>
<html><a name="HC025047"></a> <br><a name="P025072"></a><div class="PA" style="color: black; "><ol type="1"> <li>Benign tumor derived from ependymal cells (<span>[[Fig. 25-35D|Figure 25-35]]</span>)</li><li>Arises in cauda equina in adults</li><li>Arises in fourth ventricle in children</li> </ol>
</div></html>
<html><a name="HC025048"></a> <br><a name="P025073"></a><div class="PA" style="color: black; "><ol type="1"> <li>Malignant small cell tumor</li><ul> <li>Primarily occurs in children
<blockquote style="color: blue; ">Medulloblastoma: small cell tumor of cerebellum</blockquote></li> </ul><li>Arises from the external granular cell layer of the cerebellum (<span>[[Fig. 25-35E|Figure 25-35]]</span>)</li><li>Often seeds the neuraxis and invades the fourth ventricle</li> </ol>
</div></html>
<html><a name="HC025049"></a> <br><a name="P025074"></a><div class="PA" style="color: black; "><ol type="1"> <li>Benign tumor derived from oligodendrocytes</li><ul> <li>Primarily occurs in adults</li> </ul><li>Frontal lobe tumor that frequently calcifies
<blockquote style="color: blue; ">Oligodendroglioma: frontal lobe calcifications in an adult</blockquote></li> </ol>
</div></html>
<html><a name="HC025050"></a> <br><a name="P025075"></a><div class="PA" style="color: black; "><ol type="1"> <li>Majority are metastatic high-grade B-cell non-Hodgkin's lymphomas.</li><li>Primary CNS lymphomas
<blockquote style="color: blue; ">Primary CNS lymphoma: occurs in AIDS; EBV-mediated cancer</blockquote></li><ol type="a"> <li>Most often associated with AIDS</li><li>Epstein-Barr virus (EBV)-mediated B-cell lymphomas</li><li>Rapidly increasing due to the increase in AIDS</li> </ol> </ol>
</div></html>
<html><a name="HC025051"></a> <br><a name="P025076"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Most common brain malignancy</blockquote>
<ol type="1"> <li>Most common brain malignancy: metastasis (<span>[[Fig. 25-35F|Figure 25-35]]</span>)</li><li>In order of decreasing frequency:</li><ul> <li>Lung, breast, skin (melanoma), kidney, gastrointestinal tract</li> </ul> </ol>
</div></html>
<html><a name="HC025020"></a> <br><a name="P025036"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hematogenous spread (most common)</li><li>Traumatic implantation</li><li>Local extension from nearby infection</li><li>Ascent of peripheral nerve</li> </ol>
</div></html>
<html><a name="HC025021"></a> <br><a name="P025037"></a><div class="PA" style="color: black; "><ol type="1"> <li>Inflammation of pia mater covering the brain (<span>[[Fig. 25-22|Figure 25-22]]</span>)
<blockquote style="color: blue; ">Meningitis: inflammation of pia mater</blockquote></li><li>Usually due to hematogenous spread; mechanism for bacterial meningitis:
<blockquote style="color: blue; ">Bacterial meningitis: majority of organisms originate in nasopharynx</blockquote></li><ol type="a"> <li>Adherence of bacteria to mucosa of nasopharynx</li><li>Bacteremia</li><li>Translocation through blood-brain barrier (BBB)</li><ul> <li>Involves bacterial lysins</li> </ul><li>Bacteria in subarachnoid space attract neutrophils.</li><li>Acute meningitis</li> </ol><li>Risk factors in children</li><ol type="a"> <li>Undernutrition; otitis media</li><li>Pneumonia; immunodeficiency</li><li>Viral infection; sickle cell disease</li><li>Craniofacial abnormality</li> </ol><li>Viral meningitis
<blockquote style="color: blue; ">Viral meningitis: most often transmitted by fecal-oral route</blockquote></li><ol type="a"> <li>Most transmitted by fecal-oral route</li><li>Respiratory route less common</li> </ol><li>Clinical findings in meningitis
<blockquote style="color: blue; ">Meningitis: nuchal rigidity</blockquote></li><ul> <li>Fever, nuchal rigidity, headache</li> </ul><li>Complications of meningitis</li><ol type="a"> <li>Seizures; focal neurologic deficits</li><li>Cranial nerve palsies</li><li>Sensorineural hearing loss</li><li>Communicating and noncommunicating hydrocephalus</li> </ol><li>Laboratory findings in viral meningitis (<span>[[Table 25-1|Table 25-1. CEREBROSPINAL FLUID (CSF) FINDINGS IN VIRAL, BACTERIAL, AND FUNGAL MENINGITIS]]</span>; see also <span>[[Box 25-1|BOX 25-1 CEREBROSPINAL FLUID (CSF) ANALYSIS]]</span>)
<blockquote style="color: blue; ">Meningitis: ↑ CSF protein (viral, bacterial, fungal); ↓ CSF glucose (bacterial, fungal)</blockquote></li><ol type="a"> <li>Increased CSF protein</li><ul> <li>Due to increased vessel permeability</li> </ul><li>Increased total CSF leukocyte count</li><ul> <li>Initially neutrophils but converts to lymphocytes in 24 hours</li> </ul><li>Normal CSF glucose</li> </ol><li>Laboratory findings in bacterial meningitis (see <span>[[Table 25-1|Table 25-1. CEREBROSPINAL FLUID (CSF) FINDINGS IN VIRAL, BACTERIAL, AND FUNGAL MENINGITIS]]</span> and <span>[[Box 25-1|BOX 25-1 CEREBROSPINAL FLUID (CSF) ANALYSIS]]</span>)</li><ol type="a"> <li>Increased CSF protein</li><li>Increased total CSF leukocyte count</li><li>Decreased CSF glucose</li> </ol> </ol>
</div></html>
<html><a name="HC025022"></a> <br><a name="P025038"></a><div class="PA" style="color: black; "><ol type="1"> <li>Inflammation of the brain
<blockquote style="color: blue; ">Encephalitis: inflammation of brain; headache; drowsiness; coma</blockquote></li><li>Clinical findings</li><ol type="a"> <li>Fever, headache</li><li>Impaired mental status, drowsiness</li> </ol> </ol>
</div></html>
![[25.V.A.Pathogenesis]]
<<tiddler [[25.V.A.Pathogenesis]]>>
![[25.V.B.Meningitis]]
<<tiddler [[25.V.B.Meningitis]]>>
![[25.V.C.Encephalitis]]
<<tiddler [[25.V.C.Encephalitis]]>>
![[25.V.D.Cerebral abscess]]
<<tiddler [[25.V.D.Cerebral abscess]]>>
![[25.V.E.Viral CNS infections (Tables 25-2 and 25-3 and Figs. 25-24 and 25-25)]]
<<tiddler [[25.V.E.Viral CNS infections (Tables 25-2 and 25-3 and Figs. 25-24 and 25-25)]]>>
![[25.V.F.Bacterial CNS infections (Table 25-4)]]
<<tiddler [[25.V.F.Bacterial CNS infections (Table 25-4)]]>>
![[25.V.G.Fungal and parasitic CNS infections (Table 25-5 and Fig. 25-26)]]
<<tiddler [[25.V.G.Fungal and parasitic CNS infections (Table 25-5 and Fig. 25-26)]]>>
<html><a name="HC025023"></a> <br><a name="P025039"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Cerebral abscess: hematogenous; contiguous spread</blockquote>
<ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Spread from an adjacent focus of infection (e.g., sinuses)</li><li>Hematogenous spread (e.g., infective endocarditis)</li> </ol><li>Single or multiple lesions (<span>[[Fig. 25-23|Figure 25-23]]</span>)</li> </ol>
</div></html>
<html><a name="HC025024"></a><span>[[25-25|Figure 25-25]]</span> <br><span>[[Figs. 25-24|Figure 25-24]]</span> <br><span>[[25-3|Table 25-3. SLOW VIRUS DISEASES OF THE CENTRAL NERVOUS SYSTEM]]</span> <br><span>[[Tables 25-2|Table 25-2. VIRAL INFECTIONS OF THE CENTRAL NERVOUS SYSTEM]]</span> <br> <br> </html>
<html><a name="HC025025"></a><span>[[Table 25-4|Table 25-4. BACTERIAL INFECTIONS OF THE CENTRAL NERVOUS SYSTEM]]</span> <br> <br> </html>
<html><a name="HC025026"></a><span>[[Fig. 25-26|Figure 25-26]]</span> <br><span>[[Table 25-5|Table 25-5. FUNGAL AND PARASITIC INFECTIONS OF THE CENTRAL NERVOUS SYSTEM]]</span> <br> <br></html>
<html><a name="HC025028"></a> <br><a name="P025044"></a><div class="PA" style="color: black; "><ol type="1"> <li>Destruction of normal myelin</li><ul> <li>Example-multiple sclerosis</li> </ul><li>Production of abnormal myelin</li><ul> <li>Example-leukodystrophy</li> </ul><li>Destruction of oligodendrocytes</li><ul> <li>Examples-multiple sclerosis, slow virus infections</li> </ul> </ol>
</div></html>
<html><a name="HC025029"></a> <br><a name="P025045"></a><div class="PA" style="color: black; "><ol type="1"> <li>Multiple sclerosis (MS)
<blockquote style="color: blue; ">MS: most common demyelinating disease</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Most common demyelinating disease</li><li>(2) Most common debilitating disease among young adults</li><li>(3) Female predominance</li><ul> <li>Occurs most often in women 20 to 40 years of age</li> </ul> </ul><li>Many subtypes</li><li>Pathogenesis
<blockquote style="color: blue; ">MS: CD4 T cells react against self antigens in myelin sheath; cytokines activate macrophages that destroy myelin</blockquote></li><ul> <li>(1) Autoimmune disease initiated by:</li><ul> <li>(a) Genetic factors (e.g., HLA-DR2)
<blockquote style="color: blue; ">MS: genetic factors and environmental triggers</blockquote></li><li>(b) Environmental triggers</li><ul> <li>Microbial pathogens (e.g., Epstein-Barr virus, human herpes virus 6, <i>Chlamydophilia pneumoniae</i>), vitamin D, sun exposure</li> </ul> </ul><li>(2) Environmental trigger activates helper T cells whose antigen-specific receptors recognize CNS myelin basic protein (other antigens as well) as an antigen.</li><li>(3) T cells release cytokines that activate macrophages, which also release cytokines (e.g., tumor necrosis factor-α) that destroy the myelin sheath as well as oligodendrocytes that synthesize myelin (type IV hypersensitivity).</li><li>(4) Antibodies directed against the myelin sheath and oligodendrocytes may also be involved (type II hypersensitivity).</li> </ul><li>Gross and microscopic findings</li><ul> <li>(1) Demyelinating plaques occur in white mater of brain/spinal cord (<span>[[Fig. 25-27A and B|Figure 25-27]]</span>).</li><ul> <li>White mater looks like gray mater in areas of demyelination.
<blockquote style="color: blue; ">Demyelinating plaques: white mater looks like gray mater</blockquote></li> </ul><li>(2) Inflammatory infiltrate in plaques is composed predominantly of CD4 T cells and microglial cells with phagocytosed lipid.</li> </ul><li>Clinical findings</li><ul> <li>(1) Episodic course punctuated by acute relapses and remissions (80-90%)</li><li>(2) Sensory dysfunction</li><ul> <li>(a) Paresthesias
<blockquote style="color: blue; ">Sensory dysfunction: paresthesias; loss pain/temperature/vibratory sensation</blockquote></li><li>(b) Loss of pain/temperature sensation</li><li>(c) Loss of vibratory sensation</li> </ul><li>(3) Upper motor neuron (UMN) dysfunction
<blockquote style="color: blue; ">UMN dysfunction: spasticity; ↑ DTRs; muscle spasm; Babinski; weakness</blockquote></li><ul> <li>(a) Spasticity</li><li>(b) Increased deep tendon reflexes (DTRs)</li><li>(c) Muscle spasms</li><li>(d) Extensor plantar response (Babinski)</li><li>(e) Weakness</li><ul> <li>Shoulder abduction; finger extension; foot dorsiflexion; hip/knee flexion</li> </ul> </ul><li>(4) Autonomic dysfunction
<blockquote style="color: blue; ">Autonomic dysfunction: urge incontinence; sexual dysfunction; bowel motility dysfunction</blockquote></li><ul> <li>(a) Urge incontinence</li><ul> <li>Hyperactive detrusor muscle (refer to <span macro="tag [[20 Lower Urinary Tract and Male Reproductive Disorders]] [[Chapter 20]]"></span>)</li> </ul><li>(b) Sexual dysfunction</li><li>(c) Bowel motility problems</li> </ul><li>(5) Optic neuritis</li><ul> <li>(a) Inflammation of the optic nerve
<blockquote style="color: blue; ">MS: blurry vision due to optic neuritis; MS most common cause</blockquote></li><ul> <li>MS is the most common cause of optic neuritis.</li> </ul><li>(b) Blurry vision or sudden loss of vision</li> </ul><li>(6) Cerebellar ataxia</li><li>(7) Scanning speech (sound drunk)
<blockquote style="color: blue; ">SIN: scanning speech, intention tremor, nystagmus</blockquote></li><li>(8) Intention tremor, nystagmus</li><li>(9) Bilateral internuclear ophthalmoplegia (INO; <span>[[Fig. 25-27C|Figure 25-27]]</span>)</li><ul> <li>Demyelination of medial longitudinal fasciculus (MLF)
<blockquote style="color: blue; ">Bilateral INO: pathognomonic for MS; demyelination of MLF</blockquote></li> </ul><li>(10) Flexion of the neck produces an electrical sensation down the spine.</li> </ul><li>Laboratory findings (see <span>[[Box 25-1|BOX 25-1 CEREBROSPINAL FLUID (CSF) ANALYSIS]]</span>)</li><ul> <li>(1) Increased CSF leukocyte count
<blockquote style="color: blue; ">Lab: ↑ CSF lymphs, CSF protein, CSF MBP; normal CSF glucose</blockquote></li><ul> <li>Primarily CD4 T lymphocytes</li> </ul><li>(2) Increased CSF protein</li><ul> <li>Primarily an increase in γ-globulins</li> </ul><li>(3) Increased CSF myelin basic protein</li><ul> <li>Indicates active disease</li> </ul><li>(4) Normal CSF glucose</li><li>(5) High-resolution electrophoresis shows oligoclonal bands.
<blockquote style="color: blue; ">Oligoclonal bands in high-resolution electrophoresis: sign of demyelination</blockquote></li><ul> <li>(a) Discrete bands of protein in the γ-globulin region (<span>[[Fig. 25-27D|Figure 25-27]]</span>)</li><li>(b) Sign of demyelination</li> </ul><li>(6) MRI is extremely sensitive in detecting demyelinating plaques (<span>[[Fig. 25-27E|Figure 25-27]]</span>).</li> </ul><li>Diagnosis</li><ul> <li>(1) Spinal tap (see earlier text and <span>[[Box 25-1|BOX 25-1 CEREBROSPINAL FLUID (CSF) ANALYSIS]]</span>)</li><li>(2) MRI with gadolinium (most sensitive test)</li> </ul><li>Treatment</li><ul> <li>(1) Acute relapse</li><ul> <li>High dose methylprednisolone</li> </ul><li>(2) Chronic</li><ul> <li>(a) Disease modifying drugs-e.g., interferon-beta</li><li>(b) Monoclonal antibody-natalizumab</li><li>(c) Cytotoxic-cyclophosphamide; methotrexate; azathioprine</li> </ul> </ul><li>Prognosis</li><ul> <li>(1) Varies with the type of disease</li><li>(2) On average, ∼70% of patients with MS are alive 25 years after their diagnosis.</li> </ul> </ol><li>Central pontine myelinolysis (CPM; <span>[[Fig. 25-28|Figure 25-28]]</span>)</li><ol type="a"> <li>Most often occurs in alcoholics who have hyponatremia
<blockquote style="color: blue; ">CPM: due to rapid IV correction of hyponatremia</blockquote></li><li>Rapid intravenous correction causes demyelination in the basis pontis.</li><li>Treatment is supportive.</li> </ol><li>Viral infections with direct infection of oligodendrocytes</li><ul> <li>Examples-subacute sclerosing panencephalitis, progressive multifocal leukoencephalopathy</li> </ul> </ol>
</div></html>
<html><a name="HC025030"></a> <br><a name="P025046"></a><div class="PA" style="color: black; "><ul> <li>Leukodystrophies are inborn errors of metabolism.</li> </ul>
<ol type="1"> <li>Adrenoleukodystrophy</li><ol type="a"> <li>X-linked recessive (XR) disorder
<blockquote style="color: blue; ">Adrenoleukodystrophy: XR; peroxisomal enzyme deficiency in β-oxidation of FAs</blockquote></li><li>Enzyme deficiency in β-oxidation of fatty acids (FAs) in peroxisomes</li><ul> <li>Results in accumulation of long-chain fatty acids</li> </ul><li>Causes generalized loss of myelin in the brain and adrenal insufficiency</li> </ol><li>Metachromatic leukodystrophy
<blockquote style="color: blue; ">Metachromatic leukodystrophy: LSD; deficiency arylsulfatase A</blockquote></li><ol type="a"> <li>Autosomal recessive disorder</li><ul> <li>Lysosomal storage disease (LSD)</li> </ul><li>Deficiency of arylsulfatase A</li><ul> <li>Results in accumulation of sulfatides</li> </ul> </ol><li>Krabbe's disease</li><ol type="a"> <li>Autosomal recessive disorder</li><ul> <li>LSD
<blockquote style="color: blue; ">Krabbe's disease: LSD; deficiency galactocerebroside β-galactocerebrosidase</blockquote></li> </ul><li>Galactocerebroside β-galactocerebrosidase deficiency</li><ul> <li>Leads to accumulation of galactocerebroside</li> </ul><li>Brain shows large, multinucleated, histiocytic cells (globoid cells).</li> </ol> </ol>
</div></html>
![[25.VI.A.Pathogenesis]]
<<tiddler [[25.VI.A.Pathogenesis]]>>
![[25.VI.B.Acquired disorders]]
<<tiddler [[25.VI.B.Acquired disorders]]>>
![[25.VI.C.Hereditary disorders]]
<<tiddler [[25.VI.C.Hereditary disorders]]>>
<html><a name="HC025032"></a> <br><a name="P025053"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology
<blockquote style="color: blue; ">AD: most common overall cause of dementia</blockquote></li><ol type="a"> <li>Most common cause of dementia (50-75% of all cases)</li><ul> <li>(1) Sporadic late onset type of AD (most common)
<blockquote style="color: blue; ">AD: sporadic late onset type most common type</blockquote></li><li>(2) Sporadic early onset type of AD (before age 65)</li><ul> <li>Related to apolipoprotein gene E, allele ≥4</li> </ul><li>(3) Familial early onset type of AD (<1% of cases)</li><ul> <li>(a) Mutations of amyloid precursor protein (APP) on chromosome 21</li><li>(b) Mutations in presenilin 1 on chromosome 14</li><li>(c) Mutations in presenilin 2 on chromosome 1</li> </ul> </ul><li>Prevalence increases with age.
<blockquote style="color: blue; ">AD: prevalence increases with age</blockquote></li><ul> <li>(1) It is <1% in the 60- to 64-year-old age group.</li><li>(2) It is 40% to 50% by the age of 95.</li> </ul><li>Trisomy 21 (Down syndrome) has a strong association with AD.</li><ul> <li>By 40 years of age, most Down syndrome patients have AD.</li> </ul> </ol><li>Role of β-amyloid (Aβ) protein in causing AD
<blockquote style="color: blue; ">AD: ↑ Aβ → neurotoxic</blockquote></li><ol type="a"> <li>Aβ is neurotoxic and damages neurons in the following sites:</li><ul> <li>(1) Medial temporal lobe structures</li><li>(2) Frontal cortex, especially the entorhinal cortex and hippocampus</li> </ul><li>Pivotal role of activated glycogen synthase kinase-3β (GSK) in neurotoxicity of Aβ</li><ul> <li>(1) Activation of GSK causes phosphorylation of Aβ, which in turn, produces:</li><ul> <li>(a) Neuronal and synaptic dysfunction</li><li>(b) Signaling for neuronal apoptosis</li> </ul><li>(2) Phosphorylated Aβ also has a positive feedback on GSK; hence, keeping the cycle of neurotoxicity in motion
<blockquote style="color: blue; ">Activated GSK-3β: phosphorylates Aβ → neurotoxic</blockquote></li><li>(3) Initial activation of GSK has been traced to dysfunction within the Wnt (Wingless integration pathway), which is a family of genes normally involved in:</li><ul> <li>(a) Neuronal development during embryogenesis</li><li>(b) Normal neuronal function</li> </ul><li>(4) Normally, the Wnt signaling pathway inactivates GSK, hence preventing phosphorylation of Aβ and its harmful effect on neurons.</li><li>(5) However, if the Wnt signaling pathway is dysfunctional, GSK remains activated leading to phosphorylation of Aβ and its neurotoxic effects (e.g., apoptosis of neurons).
<blockquote style="color: blue; ">Aβ: can be converted into amyloid; deposits in cerebral vessels</blockquote></li> </ul><li>Aβ also deposits in the wall of cerebral vessels.</li><ul> <li>Important in producing amyloid angiopathy (see later text)</li> </ul><li>Aβ stains positive with Congo red and has apple-green birefringence with polarization (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>).</li><li>Aβ is a metabolic product of APP.
<blockquote style="color: blue; ">Aβ: metabolic product of APP; coded for on chromosome 21</blockquote></li><ul> <li>(1) APP is normally coded for on chromosome 21.</li><li>(2) Defects in metabolism of APP by secretases cause an increase in Aβ.</li><li>(3) α-Secretases cleave APP into fragments that <i>cannot</i> produce Aβ.
<blockquote style="color: blue; ">Secretases: β-secretases followed by γ-secretases cleave APP to produce Aβ</blockquote></li><li>(4) β-Secretases followed by γ-secretases cleave APP into fragments that are converted to Aβ.</li><li>(5) In the sporadic early onset type of AD, apolipoprotein gene E, allele ≥4 codes for a product that cannot eliminate Aβ from the brain leading to early onset of neurotoxicity.
<blockquote style="color: blue; ">Insulin degrading enzyme: involved in clearance of Aβ</blockquote></li> </ul><li>Insulin degrading enzyme</li><ul> <li>(1) Involved in the clearance of Aβ</li><li>(2) Insulin resistance syndromes (type 2 diabetes; metabolic syndrome) have increased risk for AD, because increased insulin lowers insulin degrading enzyme, which increases Aβ.
<blockquote style="color: blue; ">Apo gene E, allele ε4: sporadic early onset AD</blockquote></li> </ul> </ol><li>Role of tau protein in AD</li><ol type="a"> <li>Normal function is to maintain microtubules in neurons.</li><ul> <li>Assembles and supports scaffolding important in neuron structure and function</li> </ul><li>Activated GSK enhances hyperphosphorylation of tau protein.
<blockquote style="color: blue; ">Activated GSK-3β: hyperphosphorylates tau protein</blockquote></li><ul> <li>(1) This process causes the protein to change shape and cluster into fibers.</li><li>(2) Fibers appear as neurofibrillary (NF) tangles (twisted fibers) in the cytoplasm.</li><ul> <li>Best visualized with silver stains (<span>[[Fig. 25-29|Figure 25-29]]</span>)
<blockquote style="color: blue; ">NF tangle: hyperphosphorylated tau protein in neuron</blockquote></li> </ul><li>(3) NF tangles produce neuronal dysfunction including death of the neuron.</li><li>(4) Pin 1 enzyme (prolyl isomerase) normally strips excess phosphate molecules from NF, restoring it to its original shape; however, in some cases of AD, this enzyme is absent or dysfunctional.
<blockquote style="color: blue; ">PIN 1 enzyme: dephosphorylates hyperphosphorylated tau protein; deficient in some cases of AD</blockquote></li> </ul> </ol><li>Gross and microscopic findings</li><ol type="a"> <li>Cerebral atrophy with dilation of ventricles (hydrocephalus ex vacuo)</li><ul> <li>(1) Due to loss of neurons in the temporal, frontal, and parietal lobes</li><li>(2) Occipital lobe is usually spared.</li> </ul><li>Presence of NF tangles in the cytoplasm of neurons</li><ul> <li>(1) Best visualized with silver stains (see <span>[[Fig. 25-29|Figure 25-29]]</span>)</li><li>(2) They may occur in other disorders.</li><ul> <li>Elderly patients <i>without</i> dementia, Huntington's disease, Niemann-Pick disease
<blockquote style="color: blue; ">AD: ↑ density of NF tangles and senile (neuritic) plaques in the brain</blockquote></li> </ul> </ul><li>Senile (neuritic) plaques</li><ul> <li>(1) Core of Aβ surrounded by neuronal cell processes containing tau protein, microglial cells, and astrocytes (<span>[[Fig. 25-30|Figure 25-30]]</span>)</li><ul> <li>Located in the gray mater.
<blockquote style="color: blue; ">Senile (neuritic) plaques: core of Aβ surrounded by neuronal cell processes with tau protein</blockquote></li> </ul><li>(2) Aβ stains with Congo red (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>).</li><li>(3) Best visualized with silver stains</li><li>(4) Are also normally present in the brains of elderly people</li> </ul><li>Amyloid angiopathy</li><ul> <li>(1) Aβ is present in cerebral vessels.</li><li>(2) Causes weakening of vessels with increased risk for hemorrhage
<blockquote style="color: blue; ">Amyloid angiopathy: risk for cerebral hemorrhage</blockquote></li> </ul><li>Confirmation of Alzheimer's disease</li><ul> <li>(1) Requires postmortem examination of the brain</li><li>(2) Must be widespread presence of NF tangles and senile plaques
<blockquote style="color: blue; ">Confirmation of AD: must be made at autopsy</blockquote></li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Prominent early sign is the decline in short-term memory.</li><li>Another early sign is loss of smell.</li><ul> <li>Dysfunction in entorhinal cortex</li> </ul><li>Patients with mild to moderate disease have only cognitive defects.</li><li>Additional deficits accumulate, including changes in behavior, judgment, language, and abstract thought.
<blockquote style="color: blue; ">AD: prominent early sign is decline in short-term memory</blockquote></li><li>Even later in the course, functional deficits manifest in the patient not being able to care for themselves.</li><li><i>No</i> focal neurologic deficits are present early in the disease.</li><li>Patients usually die of an infection.</li><ul> <li>Example-intercurrent bronchopneumonia</li> </ul> </ol><li>Presumptive diagnosis is made with mental status testing; tests for:
<blockquote style="color: blue; ">AD: presumptive diagnosis with mental status testing; rule out all other causes of dementia</blockquote></li><ol type="a"> <li>Orientation</li><li>Attention</li><li>Verbal recall</li><li>Language</li><li>Visual-spatial skills</li> </ol><li>Positron emission tomography (PET) is useful the differential diagnosis of dementia.</li><li>Treatment</li><ol type="a"> <li>Cholinesterase inhibitors</li><ul> <li>Increase synaptic transmission</li> </ul><li>Memantine (blocks glutamate receptors)</li> </ol> </ol>
</div></html>
<html><a name="HC025033"></a> <br><a name="P025054"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology
<blockquote style="color: blue; ">Parkinsonism: alteration in dopaminergic pathways involved in voluntary muscle movement</blockquote></li><ol type="a"> <li>Group of disorders that alter dopaminergic pathways involved in voluntary muscle movement</li><ul> <li>(1) Striatal system is involved in voluntary muscle movement.</li><ul> <li>Substantia nigra, caudate, putamen, globus pallidus, subthalamus, thalamus</li> </ul><li>(2) Dopamine is the principal neurotransmitter in the nigrostriatal tract.</li><ul> <li>Connects the substantia nigra with the caudate and putamen
<blockquote style="color: blue; ">Dopamine: principal neurotransmitter in nigrostriatal tract</blockquote></li> </ul> </ul><li>Incidence increases with age.</li><li>Idiopathic Parkinson's disease is the most common type (see below).</li><li>Other causes of parkinsonism</li><ul> <li>(1) Encephalitis, ischemia</li><li>(2) Chronic carbon monoxide poisoning</li><ul> <li>Causes necrosis of globus pallidus</li> </ul><li>(3) Wilson's disease</li><li>(4) Addiction to MPTP, a derivative of meperidine</li><ul> <li>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</li> </ul><li>(5) Antipsychotic drugs (e.g., phenothiazines)</li> </ul> </ol><li>Idiopathic Parkinson's disease
<blockquote style="color: blue; ">Idiopathic Parkinson's disease: most common cause of parkinsonism</blockquote></li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Occurs between 45 and 65 years of age</li><li>(2) Distribution is equal in men and women.</li><li>(3) Most cases are sporadic.</li> </ul><li>Pathophysiology
<blockquote style="color: blue; ">Idiopathic Parkinson's disease: depigmentation substantia nigra neurons; ↓ dopamine</blockquote></li><ul> <li>(1) Degeneration/depigmentation of neurons in substantia nigra (<span>[[Fig. 25-31|Figure 25-31]]</span>)</li><li>(2) Causes deficiency of dopamine</li><li>(3) Neurons contain intracytoplasmic, eosinophilic bodies called Lewy bodies.</li><ul> <li>Ubiquinated damaged neurofilaments (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Muscle rigidity</li><ul> <li>(a) Slowness of voluntary muscle movement (bradykinesia)
<blockquote style="color: blue; ">Clinical: rigidity, resting tremor, bradykinesia</blockquote></li><li>(b) Cogwheel rigidity on physical examination</li> </ul><li>(2) Resting tremor</li><ul> <li>(a) "Pill rolling" between thumb and index fingers</li><li>(b) Illegible handwriting</li> </ul><li>(3) Expressionless face ("poker face"), stooped posture
<blockquote style="color: blue; ">Idiopathic Parkinsonism: expressionless face; blepharospasm; seborrheic dermatitis</blockquote></li><li>(4) Difficulty in initiating first step; shuffling gait</li><li>(5) Blepharospasm; postural instability</li><li>(6) Commonly have severe seborrheic dermatitis (refer to <span macro="tag [[24 Skin Disorders]] [[Chapter 24]]"></span>)</li><li>(7) Dementia in some cases</li> </ul> </ol><li>Treatment</li><ol type="a"> <li>Avoid drugs that worsen parkinsonism-neuroleptics, antiemetics, monoamine oxidase (MAO) inhibitors</li><li>Levodopa-transformed into dopamine</li><li>Carbidopa, benserazide-dopa decarboxylase inhibitors</li><li>Bromocriptine, pergolide-dopamine agonists</li><li>Selegiline, rasagiline-inhibit monoamine oxidase-B, which inhibits breakdown of dopamine</li><li>Specialized surgical procedures</li> </ol> </ol>
</div></html>
<html><a name="HC025034"></a> <br><a name="P025055"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal dominant disease
<blockquote style="color: blue; ">HD: AD; trinucleotide repeat disorder</blockquote></li><li>Trinucleotide repeat disorder (CAG) involving chromosome 4 (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)</li><li>Delayed appearance of symptoms until 30 to 40 years of age</li><li>No gender dominance</li> </ol><li>Atrophy/loss of striatal neurons
<blockquote style="color: blue; ">HD: atrophy of caudate nucleus, putamen, globus pallidus</blockquote></li><ul> <li>Caudate, putamen, globus pallidus (<span>[[Fig. 25-32|Figure 25-32]]</span>)</li> </ul><li>Clinical findings</li><ol type="a"> <li>Chorea</li><ul> <li>(1) Irregular, rapid, nonstereotyped involuntary movements</li><li>(2) Called choreoathetosis if it has a writhing quality
<blockquote style="color: blue; ">HD: chorea; oculomotor abnormalities</blockquote></li> </ul><li>Oculomotor abnormalities</li><li>Parkinsonism in later stages</li><li>Depression</li> </ol><li>Diagnosis</li><ol type="a"> <li>Genetic testing is available</li><li>Imaging studies (CT, MRI)</li><ul> <li>Atrophy of caudate and putamen</li> </ul> </ol><li>Treatment is supportive.</li> </ol>
</div></html>
<html><a name="HC025035"></a> <br><a name="P025056"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal recessive (AR) disease</li><ul> <li>(1) Trinucleotide repeat disorder (GAA)</li><li>(2) Frataxin deficiency</li><ul> <li>(a) Leads to impaired mitochondrial iron homeostasis</li><li>(b) Cells are more prone to apoptosis.
<blockquote style="color: blue; ">Friedreich's ataxia: AR; trinucleotide repeat disorder; deficiency frataxin</blockquote></li> </ul> </ul><li>Most common neurodegenerative hereditary ataxic disorder</li><li>Sites of degeneration</li><ul> <li>(1) Dorsal root ganglia</li><li>(2) Posterior columns
<blockquote style="color: blue; ">Degeneration sites: dorsal root ganglia; posterior/spinocerebellar/corticospinal tracts</blockquote></li><li>(3) Spinocerebellar tract</li><li>(4) Lateral corticospinal tracts</li><li>(5) Large sensory peripheral neurons</li> </ul><li>Hypertrophic cardiomyopathy
<blockquote style="color: blue; ">Friedreich's ataxia: hypertrophic cardiomyopathy; type 1 diabetes mellitus</blockquote></li><li>Type 1 diabetes mellitus (10%)</li> </ol><li>Clinical findings</li><ol type="a"> <li>Progressive gait ataxia</li><li>Loss of deep tendon reflexes</li><ul> <li>Initially at the ankles</li> </ul><li>Loss of vibratory sensation and proprioception</li><li>Muscle weakness in the legs</li> </ol><li>Diagnosis</li><ol type="a"> <li>Gene testing is available.</li><li>Imaging (MRI) shows spinal cord atrophy.</li> </ol><li>Treatment is supportive.</li> </ol>
</div></html>
![[25.VII.A.Alzheimer's disease (AD)]]
<<tiddler [[25.VII.A.Alzheimer's disease (AD)]]>>
![[25.VII.B.Parkinsonism]]
<<tiddler [[25.VII.B.Parkinsonism]]>>
![[25.VII.C.Huntington's disease (HD)]]
<<tiddler [[25.VII.C.Huntington's disease (HD)]]>>
![[25.VII.D.Friedreich's ataxia]]
<<tiddler [[25.VII.D.Friedreich's ataxia]]>>
![[25.VII.E.Lou Gehrig's disease (amyotrophic lateral sclerosis [ALS])]]
<<tiddler [[25.VII.E.Lou Gehrig's disease (amyotrophic lateral sclerosis [ALS])]]>>
![[25.VII.F.Werdnig-Hoffmann disease]]
<<tiddler [[25.VII.F.Werdnig-Hoffmann disease]]>>
<html><a name="HC025036"></a> <br><a name="P025057"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Degenerative disease involving upper and lower motor neurons</li><li>Symptoms usually appear between 40 and 60 years of age.</li><li>Most cases are sporadic (90-95%).</li><li>Familial cases involve mutations on chromosome 21.</li><ul> <li>(1) Defective superoxide dismutase 1</li><li>(2) Produces superoxide free radical injury of neurons
<blockquote style="color: blue; ">ALS: degeneration of LMN and UMN; atrophy of intrinsic muscles of hand (first LMN sign)</blockquote></li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Upper motor neuron (UMN) signs</li><ul> <li>Spasticity, Babinski's sign</li> </ul><li>Lower motor neuron (LMN) signs</li><ul> <li>(1) Muscle weakness</li><ul> <li>Begins with atrophy of intrinsic muscles of the hands</li> </ul><li>(2) Eventual paralysis of respiratory muscles
<blockquote style="color: blue; ">ALS: no sensory changes; bowel and bladder function intact</blockquote></li> </ul><li>No sensory changes</li><li>Preservation of bowel and bladder function</li> </ol><li>Diagnosis</li><ul> <li>Electromyography and nerve conduction studies</li> </ul><li>Treatment</li><ul> <li>Riluzole (glutamate antagonist)</li> </ul><li>Average survival time is 3 to 5 years.</li> </ol>
</div></html>
<html><a name="HC025037"></a> <br><a name="P025058"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Werdnig-Hoffmann disease: LMN disease in children</blockquote>
<ul> <li>Lower motor neuron disease that occurs in children</li> </ul>
</div></html>
<html><a name="HC025039"></a><span macro="tag [[18 Hepatobiliary and Pancreatic Disorders]] [[Chapter 18]]"></span> <br> <br><a name="P025063"></a><div class="PA" style="color: black; "><ol type="1"> <li>Autosomal recessive disease</li><ol type="a"> <li>Defect in copper excretion in bile</li><li>Defect incorporation of copper into ceruloplasmin</li><li>Leads to liver cirrhosis and excess free copper in blood</li> </ol><li>CNS findings
<blockquote style="color: blue; ">Wilson's disease: cystic degeneration of putamen</blockquote></li><ol type="a"> <li>Atrophy and cavitation of basal ganglia, particularly globus pallidus and putamen (<span>[[Fig. 25-33|Figure 25-33]]</span>)
<blockquote style="color: blue; ">Lenticular nucleus-putamen and globus pallidus in the basal ganglia</blockquote></li><li>Signs of parkinsonism, chorea, and dementia</li> </ol> </ol>
</div></html>
<html><a name="HC025040"></a> <br><a name="P025064"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Autosomal dominant disorder</li><li>Defect in porphyrin metabolism</li><ul> <li>(1) Deficiency of uroporphyrinogen synthase (porphobilinogen deaminase)</li><li>(2) Proximal increase in porphobilinogen (PBG) and δ-aminolevulinic acid (ALA)</li><li>(3) Urine is <i>colorless</i> when first voided.
<blockquote style="color: blue; ">AIP: urine colorless when first voided; exposure to light produces color</blockquote></li><ul> <li>(a) Exposure to light causes oxidation of PBG to porphobilin producing port-wine color.</li><li>(b) Classic "window-sill test"</li> </ul><li>(4) Heme has a negative feedback relationship with ALA synthase.</li><ul> <li>ALA synthase is the rate-limiting enzyme of porphyrin metabolism.</li> </ul><li>(5) Decreasing heme precipitates porphyric attacks by increasing porphyrin synthesis.</li><ul> <li>Example-drugs enhancing liver cytochrome P-450 system (e.g., alcohol)</li> </ul> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Neurologic dysfunction
<blockquote style="color: blue; ">AIP: deficiency uroporphyrinogen synthase; "bellyful of scars"; peripheral neuropathy; dementia</blockquote></li><ul> <li>(1) Recurrent bouts of severe abdominal pain simulating acute abdomen</li><li>(2) Often mistaken for a surgical abdomen</li><ul> <li>Patient has "bellyful of scars."</li> </ul> </ul><li>Psychosis</li><li>Peripheral neuropathy</li><li>Dementia</li> </ol><li>Diagnosis</li><ul> <li>Enzyme assay in RBCs</li> </ul><li>Treatment
<blockquote style="color: blue; ">Rx AIP: carbohydrate loading inhibits ALA synthase</blockquote></li><ol type="a"> <li>Avoid drugs that precipitate attacks</li><li>Carbohydrate loading with glucose</li><ul> <li>Inhibits ALA synthase</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC025041"></a><span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span> <br> <br><a name="P025065"></a><div class="PA" style="color: black; "><ol type="1"> <li>Subacute combined degeneration of the spinal cord</li><ul> <li>Posterior column and lateral corticospinal tract demyelination
<blockquote style="color: blue; ">Vitamin B<sub>12</sub> deficiency: subacute combined degeneration; dementia</blockquote></li> </ul><li>Dementia, peripheral neuropathy</li> </ol>
</div></html>
<html><a name="HC025042"></a> <br><a name="P025066"></a><div class="PA" style="color: black; "><ol type="1"> <li>Cortical and cerebellar atrophy</li><li>Central pontine myelinolysis (see <span>[[Fig. 25-28|Figure 25-28]]</span>)</li><li>Wernicke-Korsakoff syndrome</li><ol type="a"> <li>Most often due to thiamine deficiency (refer to <span macro="tag [[07 Nutritional Disorders]] [[Chapter 7]]"></span>)
<blockquote style="color: blue; ">Wernicke-Korsakoff syndrome: hemorrhage in mamillary bodies</blockquote></li><li>Gross and microscopic findings</li><ul> <li>(1) Hemorrhages with hemosiderin deposits</li><ul> <li>Mamillary bodies, wall of the third and fourth ventricles (<span>[[Fig. 25-34|Figure 25-34]]</span>)</li> </ul><li>(2) Neuronal loss, gliosis, vessel hemorrhage
<blockquote style="color: blue; ">Wernicke's encephalopathy: confusion, ataxia, nystagmus, ophthalmoplegia</blockquote></li> </ul><li>Wernicke's encephalopathy; reversible findings:</li><ul> <li>Confusion, ataxia, nystagmus, ophthalmoplegia (eye muscle weakness)</li> </ul><li>Korsakoff's psychosis</li><ul> <li>(1) Advanced irreversible stage of Wernicke's encephalopathy</li><ul> <li>Targets the limbic system</li> </ul><li>(2) Anterograde amnesia (inability to form new memories)</li><li>(3) Retrograde amnesia (inability to recall old memories)</li><li>(4) Confabulation</li><li>(5) Hallucinations
<blockquote style="color: blue; ">Alcoholics receiving IV infusion with glucose: supplement IV with thiamine to prevent acute Wernicke's encephalopathy</blockquote></li> </ul> </ol><li>Treatment</li><ul> <li>Thiamine supplementation</li> </ul> </ol>
</div></html>
![[25.VIII.A.Wilson's disease (refer to Chapter 18)]]
<<tiddler [[25.VIII.A.Wilson's disease (refer to Chapter 18)]]>>
![[25.VIII.B.Acute intermittent porphyria (AIP)]]
<<tiddler [[25.VIII.B.Acute intermittent porphyria (AIP)]]>>
![[25.VIII.C.Vitamin B12 deficiency (refer to Chapter 11)]]
<<tiddler [[25.VIII.C.Vitamin B12 deficiency (refer to Chapter 11)]]>>
![[25.VIII.D.CNS findings associated with alcohol abuse]]
<<tiddler [[25.VIII.D.CNS findings associated with alcohol abuse]]>>
<html><a name="HC025053"></a> <br><a name="P025078"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Sensory changes: demyelination-paresthesias; "glove and stocking" distribution</blockquote>
<ol type="1"> <li>Associated with demyelination and axonal degeneration</li><ol type="a"> <li>Demyelination is often segmental.</li><ul> <li>Sensory changes (e.g., paresthesias), often in a "glove and stocking" distribution</li> </ul><li>Axonal degeneration
<blockquote style="color: blue; ">Motor changes: axon degeneration-muscle fasciculations, atrophy</blockquote></li><ul> <li>Muscle fasciculations leading to muscle atrophy</li> </ul> </ol><li>Charcot-Marie-Tooth (CMT) disease</li><ol type="a"> <li>Most common hereditary neuropathy
<blockquote style="color: blue; ">CMT: most common hereditary neuropathy</blockquote></li><ul> <li>Autosomal dominant disease</li> </ul><li>Peroneal nerve neuropathy
<blockquote style="color: blue; ">CMT: lower legs have "inverted bottle" appearance</blockquote></li><ul> <li>(1) Causes atrophy of muscles of lower legs</li><li>(2) Legs have an "inverted bottle" appearance.</li> </ul><li>Treatment is supportive.</li> </ol><li>Guillain-Barré syndrome (GBS)</li><ol type="a"> <li>Epidemiology
<blockquote style="color: blue; ">GBS: most common acute peripheral neuropathy</blockquote></li><ul> <li>(1) Most common acute peripheral neuropathy</li><li>(2) Most common cause of acute flaccid paralysis</li><li>(3) Predominantly motor involvement</li><li>(4) Variants can be motor and sensory</li><li>(5) Autoimmune demyelination syndrome</li><ul> <li>(a) Involves nerve roots and peripheral nerves</li><li>(b) Common preceding infections
<blockquote style="color: blue; ">Preceding infections: <i>M. pneumoniae, C. jejuni</i>, viruses</blockquote></li><ul> <li><i>Mycoplasma pneumoniae</i> pneumonia, <i>Campylobacter jejuni</i> enteritis, viral infection (HIV, EBV, cytomegalovirus, influenza)</li> </ul> </ul> </ul><li>Rapidly progressive ascending motor weakness</li><ul> <li>(1) Less commonly descending motor weakness</li><li>(2) Usually starts in proximal muscles and eventually includes distal muscles</li><li>(3) Danger of respiratory muscle paralysis and death
<blockquote style="color: blue; ">GBS causes ascending paralysis.</blockquote></li> </ul><li>Depressed or absent deep tendon reflexes in arms and legs</li><li>"Glove and stocking" paresthesias/anesthesia</li><li>Laboratory findings (see <span>[[Box 25-1|BOX 25-1 CEREBROSPINAL FLUID (CSF) ANALYSIS]]</span>)</li><ul> <li>(1) Increased CSF protein</li><ul> <li>Oligoclonal bands present on high-resolution electrophoresis</li> </ul><li>(2) CSF glucose, cell count normal</li> </ul><li>Diagnosis</li><ul> <li>(1) Spinal tap with increased CSF protein</li><li>(2) Electromyography and nerve conduction studies</li> </ul><li>Treatment
<blockquote style="color: blue; ">Rx GBS: IV immunoglobulin or plasma exchange</blockquote></li><ul> <li>(1) Infusion IV immunoglobulin or plasma exchange</li><li>(2) Mechanical ventilation if required</li> </ul><li>Prognosis</li><ul> <li>(1) Mortality 5% to 10%</li><li>(2) Full motor recovery 60%</li><li>(3) Residual weakness 15%</li> </ul> </ol><li>Diabetes mellitus (DM)
<blockquote style="color: blue; ">DM: most common cause of peripheral neuropathy</blockquote></li><ol type="a"> <li>Most common cause of peripheral neuropathy</li><li>Due to osmotic damage of Schwann cells (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li> </ol><li>Toxin-associated neuropathies</li><ul> <li>Alcohol, heavy metals, diphtheria</li> </ul><li>Idiopathic Bell's palsy</li><ol type="a"> <li>Lower motor neuron palsy causing unilateral facial paralysis
<blockquote style="color: blue; ">Idiopathic Bell's palsy: facial muscle paralysis due to inflammation of CN VII</blockquote></li><li>Inflammatory reaction of facial nerve (CN VII)</li><ul> <li>Near the stylomastoid foramen or in the bony facial canal</li> </ul><li>May be associated with herpes simplex virus (HSV, most common), HIV, sarcoidosis, Lyme disease, pregnancy
<blockquote style="color: blue; ">Idiopathic Bell's palsy: HSV most common association</blockquote></li><ul> <li>Often bilateral in Lyme disease</li> </ul><li>Clinical findings in LMN disease (<span>[[Figs. 25-36|Figure 25-36]]</span> and <span>[[25-37|Figure 25-37]]</span>)</li><ul> <li>(1) Ipsilateral upper and lower face involvement
<blockquote style="color: blue; ">LMN Bell's palsy: ipsilateral weakness upper/lower face</blockquote></li><li>(2) Drooping of the corner of the mouth</li><li>(3) Difficulty speaking</li><li>(4) Inability to close the eye</li><li>(5) Hyperacusis in some cases
<blockquote style="color: blue; ">UMN Bell's palsy: contralateral weakness lower face; sparing of upper face</blockquote></li> </ul><li>Clinical findings in UMN disease (see <span>[[Fig. 25-37|Figure 25-37]]</span>)</li><ul> <li>(1) Contralateral lower face involvement</li><li>(2) Contralateral sparing of the upper face</li> </ul> </ol><li>Drugs producing peripheral neuropathy
<blockquote style="color: blue; ">Drugs: vincristine, hydralazine, phenytoin</blockquote></li><ul> <li>Examples-vincristine, hydralazine, phenytoin</li> </ul><li>Vitamin deficiencies producing peripheral neuropathy</li><ul> <li>Examples-deficiency of thiamine, vitamin B<sub>12</sub>, pyridoxine
<blockquote style="color: blue; ">Vitamin deficiencies: thiamine, pyridoxine, vitamin B<sub>12</sub></blockquote></li> </ul><li>Treatment of peripheral neuropathies; reduce nerve pain:</li><ol type="a"> <li>Antiseizure medications-gabapentin, carbamazepine, phenytoin</li><li>Lidocaine patch</li><li>Tricyclic antidepressants-amitriptyline, nortriptyline</li> </ol> </ol>
</div></html>
<html><a name="HC025054"></a> <br><a name="P025079"></a><div class="PA" style="color: black; "><ol type="1"> <li>Benign tumor derived from Schwann cells</li><ol type="a"> <li>CN V (trigeminal) and VIII (acoustic) may be involved.
<blockquote style="color: blue; ">Schwannoma: benign tumor of Schwann cells</blockquote></li><li>Spinal nerve roots, peripheral nerves may be involved.</li> </ol><li>Acoustic neuroma</li><ol type="a"> <li>Schwannoma of CN VIII
<blockquote style="color: blue; ">Acoustic neuroma: schwannoma of CN VIII</blockquote></li><li>Majority are located in the cerebellopontine angle.</li><ul> <li>(1) Encapsulated tumors</li><li>(2) Usually unilateral</li><li>(3) Microscopic view shows alternating dark and light areas (<span>[[Fig. 25-38|Figure 25-38]]</span>).</li> </ul><li>Clinical findings</li><ul> <li>(1) Associated with neurofibromatosis (NF2)</li><ul> <li>Usually bilateral tumors</li> </ul><li>(2) Tinnitus (ringing in the ears)
<blockquote style="color: blue; ">Acoustic neuroma: tinnitus and sensorineural hearing loss</blockquote></li><li>(3) Sensorineural deafness</li><li>(4) Sensory changes in CN V distribution</li><ul> <li>Due to tumor impingement on CN V</li> </ul> </ul><li>Treatment is surgery.</li> </ol> </ol>
</div></html>
<html><a name="HC025055"></a><span>[[Fig. 25-39|Figure 25-39]]</span> <br><span>[[Table 25-6|Table 25-6. SELECTED NERVE INJURIES]]</span> <br> <br></html>
![[25.X.A.Peripheral neuropathies]]
<<tiddler [[25.X.A.Peripheral neuropathies]]>>
![[25.X.B.Schwannoma (neurilemoma)]]
<<tiddler [[25.X.B.Schwannoma (neurilemoma)]]>>
![[25.X.C.Selected peripheral nerve injuries (Table 25-6 and Fig. 25-39)]]
<<tiddler [[25.X.C.Selected peripheral nerve injuries (Table 25-6 and Fig. 25-39)]]>>
<html><a name="HC025056"></a><span>[[Fig. 25-40|Figure 25-40]]</span> <br><span>[[Table 25-7|Table 25-7. SELECTED EYE DISORDERS]]</span> <br> <br> </html>
![[25.XI.A.Selected Eye Disorders (Table 25-7 and Fig. 25-40)]]
<<tiddler [[25.XI.A.Selected Eye Disorders (Table 25-7 and Fig. 25-40)]]>>
<html><a name="HC025057"></a><span>[[25-42|Figure 25-42]]</span> <br><span>[[Figs. 25-41|Figure 25-41]]</span> <br><span>[[Table 25-8|Table 25-8. SELECTED EAR DISORDERS]]</span> <br> <br></html>
![[25.XII.A.Selected Ear Disorders (Table 25-8 and Figs. 25-41 and 25-42)]]
<<tiddler [[25.XII.A.Selected Ear Disorders (Table 25-8 and Figs. 25-41 and 25-42)]]>>
<html><a name="HC003001a"></a> <br><span>[[Table 3-1|Table 3-1. TYPES OF IMMUNE CELLS]]</span> <br></html>
<html><a name="HC003002"></a> <br><a name="P003001"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Innate immunity: first defense against pathogens</blockquote>
<ol type="1"> <li>Nonspecific defense system against microbial pathogens</li><li>Does <i>not</i> confer long-lasting immunity against pathogens</li><li>Types of effector cells</li><ol type="a"> <li>Phagocytic cells (e.g., neutrophils, macrophages)</li><li>Natural killer (NK) cells</li><li>Dendritic cells</li><li>Microglial cells (macrophage of the central nervous system)</li><li>Eosinophils, mast cells</li><li>Mucosal epithelial cells, endothelial cells</li> </ol><li>Toll-like receptors (TLRs) in innate immunity
<blockquote style="color: blue; ">Natural killer cells: large granular lymphocytes in peripheral blood</blockquote></li><ol type="a"> <li>TLRs are membrane proteins located on the above effector cells.</li><li>TLRs recognize non-self antigens (molecules) commonly shared by pathogens.
<blockquote style="color: blue; ">TLRs: recognize non-self antigens on pathogens</blockquote></li><ul> <li>(1) Called pathogen-associated molecular patterns (PAMPs)</li><li>(2) Examples of PAMPs</li><ul> <li>(a) Endotoxin in gram-negative bacteria</li><li>(b) Peptidoglycan in gram-positive bacteria</li> </ul> </ul><li>PAMPs are <i>not</i> present on normal host effector cells.</li><li>Interaction of TLRs on effector cells with PAMPs</li><ul> <li>(1) Initiates intracellular transmission of activating signals to nuclear factor (NF)κβ</li><ul> <li>NFκβ is the "master switch" to the nucleus.
<blockquote style="color: blue; ">NFκβ: "master switch" to the nucleus</blockquote></li> </ul><li>(2) Genes are encoded for mediator production.</li><li>(3) Mediators are released into the serum or spinal fluid.</li><li>(4) Innate immunity mediators</li><ul> <li>(a) Nitric oxide</li><li>(b) Cytokines (tumor necrosis factor, interleukin 1)</li><li>(c) Adhesion molecules for neutrophils (e.g., selectins)</li><li>(d) Reactive oxygen species (e.g., peroxide)</li><li>(e) Antimicrobial peptides</li><li>(f) Chemokines</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC003003"></a> <br><a name="P003002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Antigen-dependent activation and expansion of lymphocytes</li><li>B lymphocytes produce antibodies (i.e., humoral immune response).</li><ol type="a"> <li>IgM synthesis begins at birth.</li><ul> <li>Presence of IgM at birth may indicate congenital infection (e.g., cytomegalovirus).</li> </ul><li>IgG synthesis begins at ∼2 months.</li><ul> <li>Presence of IgG at birth is maternally derived IgG.
<blockquote style="color: blue; ">IgM and IgG synthesis: begin after birth</blockquote></li> </ul> </ol><li>T cells are involved in cell-mediated immune responses.</li> </ol>
</div></html>
![[3.I.A.Cells of the immune system]]
<<tiddler [[3.I.A.Cells of the immune system]]>>
![[3.I.B.Innate (natural, nonspecific) immunity]]
<<tiddler [[3.I.B.Innate (natural, nonspecific) immunity]]>>
![[3.I.C.Acquired (specific) immunity]]
<<tiddler [[3.I.C.Acquired (specific) immunity]]>>
<html><a name="HC003005"></a> <br><a name="P003003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Known collectively as the human leukocyte antigen (HLA) system</li><li>Located on short arm of chromosome 6</li><li>Gene products are coded for on different loci (see later).</li><li>Gene products are membrane-associated glycoproteins.</li><ul> <li>Located on all nucleated cells with the <i>exception</i> of mature RBCs</li> </ul><li>HLA genes and their subtypes are transmitted to children from their parents.</li> </ol>
</div></html>
<html><a name="HC003006"></a> <br><a name="P003004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Coded by HLA-A, -B, and -C genes</li><li>Recognized by CD8 T cells and natural killer cells</li><ul> <li>Altered class I antigens (e.g., virus-infected cell) lead to destruction of the cell.</li> </ul> </ol>
</div></html>
<html><a name="HC003007"></a> <br><a name="P003005"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">APCs: B cells, macrophages, dendritic cells</blockquote>
<ol type="1"> <li>Coded by HLA-DP, -DQ, and -DR genes</li><li>Present on antigen-presenting cells (APCs)</li><ul> <li>B cells, macrophages, dendritic cells</li> </ul><li>Recognized by CD4 T cells</li> </ol>
</div></html>
<html><a name="HC003008"></a> <br><a name="P003006"></a><div class="PA" style="color: black; "><ol type="1"> <li>HLA-B27 with ankylosing spondylitis
<blockquote style="color: blue; ">HLA-B27: ankylosing spondylitis</blockquote></li><li>HLA-DR2 with multiple sclerosis</li><li>HLA-DR3 and -DR4 with type 1 diabetes mellitus</li> </ol>
</div></html>
<html><a name="HC003009"></a> <br><a name="P003007"></a><div class="PA" style="color: black; "><ol type="1"> <li>Transplantation workup</li><ul> <li>Close matches of HLA-A, -B, and -D loci in both the donor and graft recipient increase the chance of graft survival.</li> </ul><li>Determining disease risk</li><ul> <li>Example-HLA-B27-positive individuals have an increased risk of ankylosing spondylitis.</li> </ul> </ol>
</div></html>
![[3.II.A.Overview]]
<<tiddler [[3.II.A.Overview]]>>
![[3.II.B.Class I antigens]]
<<tiddler [[3.II.B.Class I antigens]]>>
![[3.II.C.Class II antigens]]
<<tiddler [[3.II.C.Class II antigens]]>>
![[3.II.D.HLA association with disease]]
<<tiddler [[3.II.D.HLA association with disease]]>>
![[3.II.E.Applications of HLA testing]]
<<tiddler [[3.II.E.Applications of HLA testing]]>>
<html><a name="HC003011"></a> <br><a name="PB003001"></a><div class="BB" style="color: rgb(47, 79, 79); ">Desensitization therapy involves repeated injections of increasingly greater amounts of allergen, resulting in production of IgG antibodies that attach to allergens and prevent them from binding to mast cells.</div><a name="P003008"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Type I hypersensitivity: IgE activation of mast cells</blockquote>
<ul> <li>IgE antibody-mediated activation of mast cells (effector cells) produces an inflammatory reaction.</li><ol type="1"> <li>IgE antibody production (sensitization)</li><ol type="a"> <li>Allergens (e.g., pollen, drugs) are first processed by APCs (macrophages or dendritic cells).</li><li>APCs interact with CD4 T<sub>H</sub>2 cells, causing interleukins (ILs) to stimulate B-cell maturation.</li><li>IL-4 causes plasma cells to switch from IgM to IgE synthesis.</li><li>IL-5 stimulates the production and activation of eosinophils.</li> </ol><li>Mast cell activation (re-exposure)
<blockquote style="color: blue; ">Mast cell activation: allergens cross-link allergen-specific antibodies</blockquote></li><ol type="a"> <li>Allergen-specific IgE antibodies are bound to mast cells.</li><li>Allergens cross-link IgE antibodies specific for the allergen on mast cell membranes.</li><li>IgE triggering causes mast cell release of preformed mediators.</li><ul> <li>(1) Early phase reaction with release of histamine, chemotactic factors for eosinophils, proteases</li><li>(2) Produces tissue swelling and bronchoconstriction</li> </ul><li>Late phase reaction</li><ul> <li>(1) Mast cells synthesize and release prostaglandins and leukotrienes.
<blockquote style="color: blue; ">Mast cells: early and late phase reactions</blockquote></li><li>(2) Enhances and prolongs acute inflammatory reaction</li> </ul> </ol><li>Tests used to evaluate type I hypersensitivity</li><ol type="a"> <li>Scratch test (best overall sensitivity)</li><ul> <li>Positive response is a histamine-mediated wheal-and-flare reaction after introduction of an allergen into the skin.</li> </ul><li>Radioimmunosorbent test
<blockquote style="color: blue; ">Anaphylactic shock: potentially fatal type I hypersensitivity reaction</blockquote></li><ul> <li>Detects specific IgE antibodies in serum that are against specific allergens</li> </ul> </ol><li>Clinical examples of type I hypersensitivity (<span>[[Table 3-2|Table 3-2. HYPERSENSITIVITY REACTIONS]]</span>)</li> </ol> </ul>
</div></html>
<html><a name="HC003012"></a> <br><a name="P003009"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Type II hypersensitivity: antibody-dependent cytotoxic reactions</blockquote>
<ul> <li>Antibody-dependent cytotoxic reactions</li><ol type="1"> <li>Complement-dependent reactions</li><ol type="a"> <li>Lysis (IgM-mediated)</li><ul> <li>(1) Antibody (IgM) directed against antigen on the cell membrane activates the complement system, leading to lysis of the cell by the membrane attack complex.</li><li>(2) Example-IgM types of cold immune hemolytic anemias (refer to <span macro="tag [[13 Lymphoid Tissue Disorders]] [[Chapter 13]]"></span>)</li><li>(3) Example-transfusion of group A blood (contains anti-B-IgM antibodies) into a group B individual (refer to <span macro="tag [[15 Immunohematology Disorders]] [[Chapter 15]]"></span>)</li> </ul><li>Lysis (IgG-mediated)</li><ul> <li>(1) IgG attaches to basement membrane/matrix → activates complement system → C5a is produced (chemotactic factor) → recruitment of neutrophils/monocytes to the activation site → release of enzymes, reactive oxygen species → damage to tissue</li><li>(2) Example-Goodpasture's syndrome with IgG antibodies directed against pulmonary and glomerular capillary basement membranes (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)</li><li>(3) Example-acute rheumatic fever with IgG antibodies directed against antigens in heart, skin, brain, subcutaneous tissue, joints (refer to <span macro="tag [[10 Heart Disorders]] [[Chapter 10]]"></span>)</li> </ul><li>Phagocytosis</li><ul> <li>(1) Fixed macrophages (e.g., in spleen) phagocytose hematopoietic cells (e.g., RBCs) coated by IgG antibodies or complement (C3b).</li><li>(2) Example-warm (IgG) immune hemolytic anemia (refer to <span macro="tag [[13 Lymphoid Tissue Disorders]] [[Chapter 13]]"></span>)</li><li>(3) Example-ABO hemolytic disease of the newborn (refer to <span macro="tag [[15 Immunohematology Disorders]] [[Chapter 15]]"></span>)</li><ul> <li>Group O mother has anti-A,B-IgG antibodies that cross the placenta and attach to fetal blood group A or B red blood cells.</li> </ul> </ul> </ol><li>Complement-independent reactions</li><ol type="a"> <li>Antibody (IgG)-dependent cell-mediated cytotoxicity</li><ul> <li>(1) Cells are coated by IgG → leukocytes (neutrophils, monocyte, NK cells) bind to IgG → activated cells release inflammatory mediators causing lysis of the cells</li><li>(2) Example-killing virus-infected cells or tumor cells</li> </ul><li>Antibody (IgE)-dependent cell-mediated cytotoxicity</li><ul> <li>Helminth in tissue is coated by IgE antibodies → eosinophil IgE receptors attach to the IgE → eosinophils release major basic protein, which kills the helminth
<blockquote style="color: blue; ">Myasthenia gravis, Graves' disease: antibodies against receptors; type II HSR</blockquote></li> </ul><li>IgG autoantibodies directed against cell surface receptors → impair function of the receptor (e.g., anti-acetylcholine receptor antibodies in myasthenia gravis) or stimulate function (e.g., anti-thyroid-stimulating hormone receptor antibodies in Graves' disease)</li> </ol><li>Tests used to evaluate type II hypersensitivity</li><ol type="a"> <li>Direct Coombs' test detects IgG and C3b attached to RBCs.</li><li>Indirect Coombs' test detects antibodies (e.g., anti-D) in serum.</li> </ol><li>Clinical examples of type II hypersensitivity (see <span>[[Table 3-2|Table 3-2. HYPERSENSITIVITY REACTIONS]]</span>)</li> </ol> </ul>
</div></html>
<html><a name="HC003013"></a> <br><a name="P003010"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Type III hypersensitivity: complement activation by circulating antigen-antibody complexes</blockquote>
<ul> <li>Activation of the complement system by circulating antigen-antibody complexes (e.g., DNA-anti-DNA complexes)</li><ol type="1"> <li>First exposure to antigen</li><ul> <li>Synthesis of antibodies</li> </ul><li>Second exposure to antigen</li><ol type="a"> <li>Deposition of antigen-antibody complexes</li><li>Complement activation, producing C5a, which attracts neutrophils that damage tissue</li> </ol><li>Arthus reaction</li><ol type="a"> <li>Localized immunocomplex reaction</li><li>Example-farmer's lung from exposure to thermophilic actinomycetes, or antigens, in air</li> </ol><li>Test used to evaluate type III hypersensitivity
<blockquote style="color: blue; ">Antibody-mediated hypersensitivity reactions: types I, II, and III</blockquote></li><ol type="a"> <li>Immunofluorescent staining of tissue biopsies</li><li>Example-glomeruli in glomerulonephritis</li> </ol><li>Clinical examples of type III hypersensitivity (see <span>[[Table 3-2|Table 3-2. HYPERSENSITIVITY REACTIONS]]</span>)</li> </ol> </ul>
</div></html>
<html><a name="HC003014"></a> <br><a name="P003011"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Type IV hypersensitivity: cellular immunity</blockquote>
<ul> <li>Antibody-independent T cell-mediated reactions (cellular-mediated immunity, CMI)</li><ol type="1"> <li>Functions of CMI</li><ol type="a"> <li>Control of infections caused by viruses, fungi, helminths, mycobacteria, intracellular bacterial pathogens</li><li>Graft rejection</li><li>Tumor surveillance</li> </ol><li>Types of reactions</li><ol type="a"> <li>Delayed reaction hypersensitivity (DRH)
<blockquote style="color: blue; ">DRH: CD4 cells interact with macrophages; TB granuloma</blockquote></li><ul> <li>CD4 cells interact with macrophages (APCs with MHC class II antigens), resulting in cytokine injury to tissue (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>).</li> </ul><li>Cell-mediated cytotoxicity</li><ul> <li>(1) CD8 T cells interact with altered MHC class I antigens on neoplastic, virus-infected, or donor graft cells, causing cell lysis.
<blockquote style="color: blue; ">CD8 T cell mediated: altered class I antigens; contact dermatitis</blockquote></li><li>(2) Contact dermatitis</li><ul> <li>CD8 T cells attack antigens in skin (e.g., poison ivy, nickel).</li> </ul> </ul> </ol><li>Test used to evaluate type IV hypersensitivity</li><ol type="a"> <li>Patch test to confirm contact dermatitis</li><ul> <li>Example-suspected allergen (e.g., nickel) placed on an adhesive patch is applied to the skin to see if a skin reaction occurs.</li> </ul><li>Skin reaction to <i>Candida</i></li><li>Quantitative count of T cells</li><li>Various mitogenic assays</li> </ol><li>Clinical examples of type IV hypersensitivity (see <span>[[Table 3-2|Table 3-2. HYPERSENSITIVITY REACTIONS]]</span>)</li> </ol> </ul>
</div></html>
![[3.III.A.Type I (immediate) hypersensitivity]]
<<tiddler [[3.III.A.Type I (immediate) hypersensitivity]]>>
![[3.III.B.Type II (cytotoxic) hypersensitivity]]
<<tiddler [[3.III.B.Type II (cytotoxic) hypersensitivity]]>>
![[3.III.C.Type III (immunocomplex) hypersensitivity]]
<<tiddler [[3.III.C.Type III (immunocomplex) hypersensitivity]]>>
![[3.III.D.Type IV hypersensitivity]]
<<tiddler [[3.III.D.Type IV hypersensitivity]]>>
<html><a name="HC003016"></a> <br><a name="P003012"></a><div class="PA" style="color: black; "><ol type="1"> <li>ABO blood group compatibility between recipients and donors
<blockquote style="color: blue; ">ABO blood group compatibility: most important requirement for successful transplantation</blockquote></li><li>Absence of preformed anti-HLA cytotoxic antibodies in recipients</li><ul> <li>People must have previous exposure to blood products to develop anti-HLA cytotoxic antibodies.</li> </ul><li>Close matches of HLA-A, -B, and -D loci between recipients and donors</li><li>Chance of a sibling in a family having another sibling with a 0, 1, or 2 haplotype match is illustrated in <span>[[Figure 3-1|Figure 3-1]]</span>.</li> </ol>
</div></html>
<html><a name="HC003017"></a> <br><a name="PB003002"></a><div class="BB" style="color: rgb(47, 79, 79); ">The fetus is an allograft that is <i>not</i> rejected by the mother. Trophoblastic tissue may prevent maternal T cells from entering fetus.</div><a name="P003013"></a><div class="PA" style="color: black; "><ol type="1"> <li>Autograft (i.e., self to self)
<blockquote style="color: blue; ">Autograft: best survival rate</blockquote></li><ul> <li>Associated with the best survival rate</li> </ul><li>Syngeneic graft (isograft)</li><ul> <li>Between identical twins</li> </ul><li>Allograft</li><ul> <li>Between genetically different individuals of the same species</li> </ul><li>Xenograft
<blockquote style="color: blue; ">Fetus: allograft not rejected by mother</blockquote></li><ol type="a"> <li>Between two species</li><li>Example-transplant of heart valve from pig to human</li> </ol> </ol>
</div></html>
<html><a name="HC003018"></a> <br><a name="PB003003"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Acute rejection</b> is potentially reversible with immunosuppressive agents, such as cyclosporine (blocks CD<sup>4</sup> T-cell release of IL-2), OKT<sup>3</sup> (monoclonal antibody against T-cell antigen recognition site), and corticosteroids (lymphotoxic). Immunosuppressive therapy is associated with an increased risk of cervical squamous cell cancer, malignant lymphoma, and squamous cell carcinoma of the skin (most common cancer).</div><a name="P003014"></a><div class="PA" style="color: black; "><ul> <li>Transplantation rejection involves a humoral or cell-mediated host response against MHC antigens in the donor graft.</li><ol type="1"> <li>Hyperacute rejection</li><ol type="a"> <li>Irreversible reaction occurs within minutes.
<blockquote style="color: blue; ">Hyperacute rejection: irreversible; type II hypersensitivity reaction</blockquote></li><li>Pathogenesis</li><ul> <li>(1) ABO incompatibility or action of preformed anti-HLA antibodies in the recipient directed against donor antigens in vascular endothelium</li><li>(2) Type II hypersensitivity reaction</li> </ul><li>Pathologic finding</li><ul> <li>Vessel thrombosis</li> </ul><li>Example-blood group A person receives a blood group B heart.</li> </ol><li>Acute rejection</li><ol type="a"> <li>Most common transplant rejection</li><li>Reversible reaction that occurs within days to weeks</li><ul> <li>(1) Type IV cell-mediated hypersensitivity</li><ul> <li>(a) Host CD4 T cells release cytokines, resulting in activation of host macrophages, proliferation of CD8 T cells, and destruction of donor graft cells.</li><li>(b) Extensive interstitial round cell lymphocytic infiltrate in the graft, edema, and endothelial cell injury</li> </ul><li>(2) Antibody-mediated type II hypersensitivity reaction
<blockquote style="color: blue; ">Acute rejection: most common type; type IV and type II hypersensitivity</blockquote></li><ul> <li>(a) Cytokines from CD4 T cells promote B-cell differentiation into plasma cells, producing anti-HLA antibodies that attack vessels in the donor graft.</li><li>(b) Vasculitis with intravascular thrombosis in recent grafts</li><li>(c) Intimal thickening with obliteration of vessel lumens in older grafts</li> </ul> </ul> </ol><li>Chronic rejection
<blockquote style="color: blue; ">Chronic rejection: irreversible</blockquote></li><ol type="a"> <li>Irreversible reaction that occurs over months to years</li><li>Pathogenesis</li><ul> <li>(1) Not well characterized
<blockquote style="color: blue; ">Immunosuppressive therapy: danger of squamous cell carcinoma</blockquote></li><li>(2) Involves continued vascular injury with ischemia to tissue</li> </ul><li>Blood vessel damage with intimal thickening and fibrosis</li> </ol> </ol> </ul>
</div></html>
<html><a name="HC003019"></a> <br><a name="P003015"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes</li><ol type="a"> <li>Potential complication in bone marrow (85% of cases) and liver transplants</li><li>Potential complication in blood transfusions given to patients with a T-cell immunodeficiency and newborns</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Donor cytotoxic T cells recognize host tissue as foreign</li><li>Proliferate in host tissue and produce severe organ damage</li> </ol><li>Clinical findings
<blockquote style="color: blue; ">GVH reaction: jaundice, diarrhea, dermatitis</blockquote></li><ol type="a"> <li>Bile duct necrosis (jaundice)</li><li>Gastrointestinal mucosa ulceration (bloody diarrhea)</li><li>Dermatitis</li> </ol><li>Treatment</li><ol type="a"> <li>Treat with anti-thymocyte globulin or monoclonal antibodies <i>before</i> grafting</li><li>Cyclosporine reduces the severity of the reaction.</li> </ol> </ol>
</div></html>
<html><a name="HC003020"></a><span>[[Table 3-3|Table 3-3. SOME TYPES OF TRANSPLANTS]]</span> <br> <br><a name="P003016"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Corneal transplants: best allograft survival rate</blockquote>
</div></html>
![[3.IV.A.Factors enhancing graft viability]]
<<tiddler [[3.IV.A.Factors enhancing graft viability]]>>
![[3.IV.B.Types of grafts]]
<<tiddler [[3.IV.B.Types of grafts]]>>
![[3.IV.C.Types of rejection]]
<<tiddler [[3.IV.C.Types of rejection]]>>
![[3.IV.D.Graft-versus-host (GVH) reaction]]
<<tiddler [[3.IV.D.Graft-versus-host (GVH) reaction]]>>
![[3.IV.E.Types of transplants (Table 3-3)]]
<<tiddler [[3.IV.E.Types of transplants (Table 3-3)]]>>
<html><a name="HC003022"></a> <br><a name="P003019"></a><div class="PA" style="color: black; "><ol type="1"> <li>Release of normally sequestered antigens (e.g., sperm)</li><li>Imbalance favoring CD4 T helper cells over CD8 T suppressor cells</li><li>Sharing of antigens between host and pathogen (mimicry)</li><ul> <li>Example-group A streptococcus antigens are similar to antigens in the human heart and other tissues in rheumatic fever.</li> </ul><li>Alteration of self-antigens by drugs or by a pathogen</li><ol type="a"> <li>Drug example-methyldopa alters Rh antigens on the surface of RBCs</li><li>Pathogen example-coxsackievirus alters β-islet cells</li> </ol><li>Abnormal immune response genes on chromosome 6 (Ir genes)</li><li>Polyclonal activation of B lymphocytes</li><ul> <li>Polyclonal activators include Epstein-Barr virus, cytomegalovirus, endotoxins</li> </ul> </ol>
</div></html>
![[3.V.A.Mechanisms of autoimmunity]]
<<tiddler [[3.V.A.Mechanisms of autoimmunity]]>>
![[3.V.B.Classification of autoimmunity]]
<<tiddler [[3.V.B.Classification of autoimmunity]]>>
![[3.V.C.Laboratory evaluation of autoimmune disease]]
<<tiddler [[3.V.C.Laboratory evaluation of autoimmune disease]]>>
![[3.V.D.Systemic lupus erythematosus]]
<<tiddler [[3.V.D.Systemic lupus erythematosus]]>>
![[3.V.E.Systemic sclerosis (scleroderma)]]
<<tiddler [[3.V.E.Systemic sclerosis (scleroderma)]]>>
![[3.V.F.Dermatomyositis (DM; with skin involvement) and polymyositis (PM; no skin involvement)]]
<<tiddler [[3.V.F.Dermatomyositis (DM; with skin involvement) and polymyositis (PM; no skin involvement)]]>>
![[3.V.G.Mixed connective tissue disease (MCTD)]]
<<tiddler [[3.V.G.Mixed connective tissue disease (MCTD)]]>>
<html><a name="HC003023"></a> <br><a name="P003020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Organ-specific disorders
<blockquote style="color: blue; ">Organ-specific disorders: Addison's disease, pernicious anemia</blockquote></li><ol type="a"> <li>Addison's disease</li><ul> <li>Immune destruction of the adrenal cortex (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li> </ul><li>Pernicious anemia</li><ul> <li>Immune destruction of parietal cells in the stomach (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)</li> </ul><li>Hashimoto's thyroiditis</li><ul> <li>Immune destruction of the thyroid (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li> </ul> </ol><li>Systemic examples
<blockquote style="color: blue; ">Systemic autoimmune disorders: SLE, rheumatoid arthritis</blockquote></li><ol type="a"> <li>Systemic lupus erythematosus (SLE; see later)</li><li>Rheumatoid arthritis (refer to <span macro="tag [[23 Musculoskeletal and Soft Tissue Disorders]] [[Chapter 23]]"></span>)</li><li>Systemic sclerosis (see later)</li> </ol> </ol>
</div></html>
<html><a name="HC003024"></a> <br><a name="P003021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Serum antinuclear antibody (ANA) test
<blockquote style="color: blue; ">Serum ANA: antibodies against DNA, histones, acidic proteins, nucleoli</blockquote></li><ol type="a"> <li>Most useful screening test for autoimmune diseases</li><li>Antinuclear antibodies are directed against various nuclear antigens.</li><ul> <li>(1) DNA</li><ul> <li>Anti-double-stranded (ds) antibodies present in SLE patients who have renal disease
<blockquote style="color: blue; ">Anti-dsDNA: SLE with glomerulonephritis</blockquote></li> </ul><li>(2) Histones</li><ul> <li>Antihistone antibodies present in drug-induced lupus</li> </ul><li>(3) Acidic proteins</li><ul> <li>(a) Anti-Smith (Sm) present in SLE</li><li>(b) Anti-ribonucleoprotein antibodies present in systemic sclerosis</li> </ul><li>(4) Nucleolar antigens</li><ul> <li>Anti-nucleolar antibodies present in systemic sclerosis</li> </ul> </ul><li>Serum ANA is a fluorescent antibody test.</li><ul> <li>(1) Provides a pattern of immunofluorescence</li><ul> <li>(a) Patterns include speckled, homogeneous, nucleolar, and rim</li><li>(b) Rim pattern correlates with anti-dsDNA antibodies and the presence of renal disease in SLE
<blockquote style="color: blue; ">Rim pattern: associated with anti-dsDNA antibodies</blockquote></li> </ul><li>(2) Provides a titer of the antibody</li> </ul> </ol><li>Specific antibody tests</li><ol type="a"> <li>Utilized in documenting organ-specific autoimmune diseases</li><li>Example-antibodies directed against the proton pump in parietal cells in pernicious anemia</li> </ol><li>Summary of autoantibodies in <span>[[Table 3-4|Table 3-4. AUTOANTIBODIES IN AUTOIMMUNE DISEASE]]</span></li> </ol>
</div></html>
<html><a name="HC003025"></a> <br><a name="PB003004"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Anticardiolipin antibodies</b> may produce a false positive syphilis serologic test by cross-reacting with cardiolipin in the rapid plasma reagin (RPR) and venereal disease research laboratory (VDRL) tests.</div><a name="P003022"></a><div class="PA" style="color: black; "><ul> <li>Connective tissue disease that mainly affects the blood, joints, skin, and kidneys</li><ol type="1"> <li>Occurs predominantly in women of childbearing age</li><li>Pathogenesis</li><ol type="a"> <li>Genetic</li><ul> <li>(1) There is an increased risk for developing SLE in family members.</li><li>(2) Genetic links appear to be located on chromosome 6.
<blockquote style="color: blue; ">SLE: genetic + environmental factors</blockquote></li> </ul><li>Environmental factors are important in exacerbating SLE or triggering its initial onset.</li><ul> <li>(1) Examples</li><ul> <li>(a) Infectious agents (viruses, bacteria)</li><li>(b) Ultraviolet light</li><li>(c) Estrogen</li><li>(d) Medications</li><li>(e) Extreme stress</li> </ul><li>(2) These factors cause destruction of cells leading to antibodies directed against various nuclear antigens (see earlier).</li><li>(3) Autoantibodies are present many years before the diagnosis of SLE, indicating that cell damage occurs prior to onset of symptoms.</li> </ul><li>An allele of STAT4 is associated with increased risk for developing SLE (also rheumatoid arthritis).</li><ul> <li>(1) STAT4 is part of a family of transcription factors.</li><li>(2) Protein products of STAT4 are essential for mediating responses to IL-12 in lymphocytes and in regulating the differentiation of T helper cells.</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Hematologic</li><ul> <li>Autoimmune hemolytic anemia, thrombocytopenia, leukopenia</li> </ul><li>Lymphatic</li><ul> <li>(1) Generalized painful lymphadenopathy</li><li>(2) Splenomegaly</li> </ul><li>Musculoskeletal</li><ul> <li>Small-joint inflammation (e.g., hands) with absence of joint deformity</li> </ul><li>Skin</li><ul> <li>(1) Immunocomplex deposition along basement membrane</li><ul> <li>Produces liquefactive degeneration</li> </ul><li>(2) Malar butterfly rash (<span>[[Fig. 3-2A|Figure 3-2]]</span>)</li> </ul><li>Renal</li><ul> <li>Diffuse proliferative glomerulonephritis (most common glomerulonephritis)</li> </ul><li>Cardiovascular
<blockquote style="color: blue; ">Most common cardiac finding in SLE: fibrinous pericarditis with effusion</blockquote></li><ul> <li>(1) Fibrinous pericarditis with or without effusion</li><li>(2) Libman-Sacks endocarditis (sterile vegetations on mitral valve; 18% of cases)</li> </ul><li>Respiratory</li><ul> <li>(1) Interstitial fibrosis of lungs</li><li>(2) Pleural effusion with friction rub</li> </ul><li>Pregnancy-related</li><ul> <li>(1) Complete heart block in newborns</li><ul> <li>Caused by IgG anti-SS-A (Ro) antibodies crossing the placenta</li> </ul><li>(2) Recurrent spontaneous abortions</li><ul> <li>Caused by antiphospholipid antibodies (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>)</li> </ul> </ul> </ol><li>Drug-induced lupus erythematosus</li><ol type="a"> <li>Associated drugs</li><ul> <li>Procainamide, hydralazine
<blockquote style="color: blue; ">Procainamide: most common drug associated with drug-induced lupus</blockquote></li> </ul><li>Features that distinguish drug-induced lupus from SLE</li><ul> <li>(1) Antihistone antibodies</li><li>(2) Low incidence of renal and CNS involvement
<blockquote style="color: blue; ">Drug-induced lupus: antihistone antibodies</blockquote></li><li>(3) Disappearance of symptoms when the drug is discontinued</li> </ul> </ol><li>Laboratory testing for SLE</li><ol type="a"> <li>Serum antinuclear antibody (ANA)
<blockquote style="color: blue; ">Screen for SLE: serum ANA</blockquote></li><ul> <li>(1) Serum ANA is the best screening test for SLE (sensitivity 99%).</li><ul> <li>False negative test results (have SLE but test is negative) are uncommon.</li> </ul><li>(2) Specificity of serum ANA is only 80%.</li><ul> <li>False positive results due to other autoimmune diseases (e.g., systemic sclerosis)</li> </ul> </ul><li>Anti-dsDNA antibodies and anti-Sm antibodies</li><ul> <li>(1) Tests used to confirm the diagnosis of SLE</li><ul> <li>They have high specificity for diagnosing SLE (i.e., few false positive results)</li> </ul><li>(2) Specificity for anti-dsDNA is 99% and 100% for anti-Sm.
<blockquote style="color: blue; ">Confirm SLE: anti-dsDNA and anti-Sm antibodies</blockquote></li> </ul><li>Anti-Ro antibodies are positive in 25% to 50% of cases.</li><li>Antiphospholipid antibodies (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>)</li><ul> <li>(1) Lupus anticoagulant and anticardiolipin antibodies</li><li>(2) Damage vessel endothelium, producing vessel thrombosis</li><li>(3) Increased incidence of strokes and recurrent spontaneous abortions</li> </ul><li>Lupus erythematosus (LE) cell
<blockquote style="color: blue; ">LE cell: neutrophil with phagocytosed, altered DNA</blockquote></li><ul> <li>(1) Neutrophil containing phagocytosed altered DNA</li><li>(2) Sensitivity 76% and specificity 97%</li> </ul><li>Serum complement</li><ul> <li>Usually decreased because of activation of complement system by immunocomplexes</li> </ul><li>Immunofluorescence testing</li><ul> <li>(1) Immunocomplexes at the dermal-epidermal junction in skin biopsies</li><ul> <li>Immunofluorescent studies identify complexes in a band-like distribution along the dermal-epidermal junction (called <i>band test</i>).</li> </ul><li>(2) Immunofluorescence studies of kidney biopsies to identify glomerulonephritis.</li> </ul> </ol><li>Prognosis</li><ol type="a"> <li>Improved survival due to advances in diagnosis and treatment (see later)</li><ul> <li>Over 90% now survive for 10 years or more</li> </ul><li>Most common cause of death is infection due to immunosuppression.</li> </ol> </ol> </ul>
</div><a name="PB003005"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Treatment for SLE</b> depends on the organ systems that are involved. Joint pain and serositis are generally controlled with NSAIDs. Treatment modalities used for cutaneous disease include topical corticosteroids, antimalarial agents, sunscreen, and immunosuppressive drugs (e.g., methotrexate or azathioprine). Renal disease is treated with cyclophosphamide. Autoimmune hemolytic anemia and thrombocytopenia are initially treated with corticosteroids; other drugs or splenectomy may be required if corticosteroids are ineffective. Tumor necrosis factor-α inhibitors are also being used in treating SLE; however, there is a danger for disseminated infections (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>).</div></html>
<html><a name="HC003026"></a> <br><a name="P003023"></a><div class="PA" style="color: black; "><ul> <li>Excessive production of collagen that primarily targets the skin (scleroderma), gastrointestinal tract, lungs, and kidneys
<blockquote style="color: blue; ">Systemic sclerosis: excess collagen deposition, digital vasculitis</blockquote></li><ol type="1"> <li>Occurs predominantly in women of childbearing age</li><li>Pathogenesis</li><ol type="a"> <li>Small-vessel endothelial cell damage produces blood vessel fibrosis and ischemic injury.</li><li>T-cell release of cytokines results in excessive collagen synthesis.</li><li>Stimulatory autoantibodies against platelet-derived growth factor</li> </ol><li>Clinical findings</li><ol type="a"> <li>Raynaud's phenomenon (<span>[[Fig. 3-2B|Figure 3-2]]</span>; refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)
<blockquote style="color: blue; ">Raynaud's phenomenon: most common initial sign of systemic sclerosis</blockquote></li><ul> <li>(1) Sequential color changes (white to blue to red) caused by digital vessel vasculitis and fibrosis</li><ul> <li>Most common initial complaint (70% of cases)</li> </ul><li>(2) Tapered fingers often with digital infarcts (<span>[[Fig. 3-2C|Figure 3-2]]</span>)</li> </ul><li>Skin</li><ul> <li>(1) Skin atrophy and tissue swelling beginning in the fingers and extending proximally</li><li>(2) Parchment-like appearance</li><li>(3) Extensive dystrophic calcification in subcutaneous tissue</li><li>(4) Tightened facial features (e.g., radial furrowing around the lips) (<span>[[Fig. 3-2D|Figure 3-2]]</span>)</li> </ul><li>Gastrointestinal</li><ul> <li>(1) Dysphagia for solids and liquids</li><ul> <li>(a) No peristalsis in the lower two thirds of the esophagus (smooth muscle replaced by collagen)</li><li>(b) Lower esophageal sphincter relaxation with reflux</li> </ul><li>(2) Small bowel</li><ul> <li>(a) Loss of villi (malabsorption)</li><li>(b) Wide-mouthed diverticula (bacterial overgrowth)</li><li>(c) Dysmotility (cramps and diarrhea)</li> </ul> </ul><li>Respiratory
<blockquote style="color: blue; ">Systemic sclerosis: respiratory failure most common cause of death</blockquote></li><ul> <li>(1) Interstitial fibrosis</li><li>(2) Respiratory failure (most common cause of death)</li> </ul><li>Renal</li><ul> <li>(1) Vasculitis involving arterioles (i.e., hyperplastic arteriolosclerosis) and glomeruli</li><li>(2) Infarctions, malignant hypertension</li> </ul> </ol><li>Laboratory findings in systemic sclerosis</li><ol type="a"> <li>Serum ANA is positive in 70% to 90% of cases.</li><li>Anti-topoisomerase antibody is positive in 30% of cases.</li><ul> <li>Extractable nuclear antibody to Scl 70.
<blockquote style="color: blue; ">Systemic sclerosis: anti-topoisomerase antibodies</blockquote></li> </ul> </ol><li>CREST syndrome</li><ul> <li>Limited sclerosis</li><ol type="a"> <li>Clinical findings</li><ul> <li>(1) C-calcification, centromere antibody</li><li>(2) R-Raynaud's phenomenon (see <span>[[Fig. 3-2B|Figure 3-2]]</span>)</li><li>(3) E-Esophageal dysmotility</li><li>(4) S-sclerodactyly (i.e., tapered, claw-like fingers; see <span>[[Fig. 3-2C|Figure 3-2]]</span>)</li><li>(5) T-telangiectasias (i.e., multiple punctate blood vessel dilations)
<blockquote style="color: blue; ">CREST syndrome = <i>c</i>alcinosis, <i>R</i>aynaud's phenomenon, <i>e</i>sophageal dysfunction, sclerodactyly, <i>t</i>elangiectasia</blockquote></li> </ul><li>Laboratory findings</li><ul> <li>Anticentromere antibodies in 50% to 90% of cases</li> </ul> </ol> </ul><li>Treatment</li><ul> <li><span style="font-variant:small-caps;">d</span>-Penicillamine; recombinant human relaxin</li> </ul> </ol> </ul>
</div></html>
<html><a name="HC003027"></a> <br><a name="P003024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Occurs predominantly in women 40 to 60 years of age</li><li>Associated with risk of malignant neoplasms (15-20% of cases), particularly lung cancer</li><li>Pathogenesis</li><ol type="a"> <li>DM is associated with antibody-mediated damage.</li><li>PM is associated with T cell-mediated damage.</li> </ol><li>Clinical findings</li><ol type="a"> <li>Muscle pain and atrophy</li><ul> <li>Shoulders are commonly involved.
<blockquote style="color: blue; ">DM/PM: heliotrope eyes; Gottron's patches</blockquote></li> </ul><li>Heliotrope eyelids or "raccoon eyes" (purple-red eyelid discoloration; <span>[[Fig. 3-2E|Figure 3-2]]</span>)</li><li>Purple papules over the knuckles and proximal interphalangeal joints (see <span>[[Fig 3-2F|Figure 3-2]]</span>)</li><ul> <li>Called Gottron's patches</li> </ul> </ol><li>Laboratory findings</li><ol type="a"> <li>Serum ANA is positive in <30% of cases.
<blockquote style="color: blue; ">DM/PM: ↑ serum creatine kinase</blockquote></li><li>Increased serum creatine kinase</li><li>Muscle biopsy shows a lymphocytic infiltrate.</li> </ol> </ol>
</div></html>
<html><a name="HC003028"></a> <br><a name="P003025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Signs and symptoms similar to SLE, systemic sclerosis, and PM
<blockquote style="color: blue; ">MCTD: anti-ribonucleoprotein antibodies</blockquote></li><li>Renal disease is uncommon.</li><li>Anti-ribonucleoprotein antibodies are positive in almost 100% of cases.</li> </ol>
</div></html>
<html><a name="HC003030"></a> <br><a name="P003028"></a><div class="PA" style="color: black; "><ol type="1"> <li>Prematurity</li><li>Autoimmune diseases (e.g., systemic lupus erythematosus)</li><li>Lymphoproliferative disorders (e.g., malignant lymphoma)</li><li>Infections (e.g., human immunodeficiency virus, HIV)</li><li>Immunosuppressive drugs (e.g., corticosteroids)</li> </ol>
</div></html>
<html><a name="HC003031"></a><span>[[Table 3-5|Table 3-5. CONGENITAL IMMUNODEFICIENCY DISORDERS]]</span> <br> <br><a name="P003029"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">IgA deficiency: most common congenital immunodeficiency</blockquote>
<ol type="1"> <li>B-cell disorders</li><ul> <li>Recurrent encapsulated bacterial infections (e.g., <i>Streptococcus pneumoniae</i>)</li> </ul><li>T-cell disorders</li><ul> <li>Recurrent infections caused by intracellular pathogens (fungi, viruses, protozoa)</li> </ul><li>Combined B- and T-cell disorders</li> </ol>
</div></html>
<html><a name="HC003032"></a> <br><a name="P003030"></a><div class="PA" style="color: black; "><ol type="1"> <li>Modes of transmission
<blockquote style="color: blue; ">AIDS: most common acquired immunodeficiency disease worldwide</blockquote></li><ol type="a"> <li>Sexual transmission (∼75% of cases)</li><ul> <li>(1) Man-to-man transmission by anal intercourse is the most common cause in the United States.</li><li>(2) Heterosexual transmission is the most common cause in developing countries.
<blockquote style="color: blue; ">AIDS: most common cause of death due to infection worldwide</blockquote></li><li>(3) Virus enters blood vessels or dendritic cells in areas of mucosal injury.</li> </ul><li>Intravenous drug abuse</li><ul> <li>Rate of HIV infection is markedly increasing in female sex partners of male intravenous drug abusers.</li> </ul><li>Other modes of transmission</li><ul> <li>(1) Vertical transmission</li><ul> <li>(a) Transplacental route, blood contamination during delivery, breast-feeding</li><li>(b) Most pediatric cases of AIDS are due to transmission of virus from mother to child.
<blockquote style="color: blue; ">Pediatric AIDS: most due to vertical transmission</blockquote></li> </ul><li>(2) Accidental needlestick</li><ul> <li>(a) Risk per accident is 0.3%.</li><li>(b) Most common mode of infection in health care workers</li> </ul><li>(3) Blood products
<blockquote style="color: blue; ">Risk per unit of blood is 1 per 2 million units of blood transfused.</blockquote></li> </ul><li>Body fluids containing HIV</li><ul> <li>(1) Blood, semen, breast milk</li><li>(2) Virus <i>cannot</i> enter intact skin or mucosa.</li> </ul> </ol><li>Etiology</li><ol type="a"> <li>RNA retrovirus</li><li>HIV-1 is the most common cause in the United States.</li><li>HIV-2 is the most common cause in developing countries.</li> </ol><li>Pathogenesis</li><ol type="a"> <li>HIV envelope protein (gp120) attaches to the CD4 molecule of T cells.</li><li>HIV infects CD4 T cells, causing direct cytotoxicity.
<blockquote style="color: blue; ">HIV: cytotoxic to CD4 T cells; loss of cell-mediated immunity</blockquote></li><li>Infection of non-T cells</li><ul> <li>(1) Can infect monocytes and macrophages in tissue (e.g., lung, brain)</li><li>(2) Can infect dendritic cells in mucosal tissue</li><ul> <li>Dendritic cells transfer virus to B-cell germinal follicles.</li> </ul><li>(3) Macrophages and dendritic cells are reservoirs for virus.</li><ul> <li>Loss of cell-mediated immunity</li> </ul> </ul><li>Reverse transcriptase</li><ul> <li>(1) Converts viral RNA into proviral double-stranded DNA</li><li>(2) DNA is integrated into the host DNA.</li> </ul> </ol><li>HIV and AIDS testing (<span>[[Table 3-6|Table 3-6. LABORATORY TESTS USED IN HIV AND AIDS]]</span>)
<blockquote style="color: blue; ">Anti-gp120: detected in ELISA test screen</blockquote></li><li>Clinical findings</li><ol type="a"> <li>Acute phase
<blockquote style="color: blue; ">Western blot: confirms HIV</blockquote></li><ul> <li>Mononucleosis-like syndrome 3 to 6 weeks after infection</li> </ul><li>Latent (chronic) phase</li><ul> <li>(1) Asymptomatic period 2 to 10 years after infection</li><li>(2) CD4 T-cell count greater than 500 cells/mm<sup>3</sup></li><li>(3) Viral replication occurs in dendritic cells (reservoir cells) in germinal follicles of lymph nodes.</li><ul> <li>Cytotoxic T cells control but do <i>not</i> clear HIV reservoirs.
<blockquote style="color: blue; ">Reservoir cell for HIV: follicular dendritic cells in lymph nodes</blockquote></li> </ul> </ul><li>Early symptomatic phase</li><ul> <li>(1) CD4 T-cell count 200 to 500 cells/mm<sup>3</sup></li><li>(2) Generalized lymphadenopathy</li><li>(3) Non-AIDS-defining infections, including hairy leukoplakia, or Epstein-Barr virus (EBV)-caused glossitis, oral candidiasis</li><li>(4) Fever, weight loss, diarrhea</li><li>Most common CNS fungal infection in AIDS: cryptococcosis
<blockquote style="color: blue; ">Most common malignancy in AIDS: Kaposi's sarcoma</blockquote></li> </ul><li>AIDS (<span>[[Table 3-7|Table 3-8. COMPLEMENT DISORDERS]]</span>)</li><ul> <li>(1) Criteria</li><ul> <li>HIV-positive with CD4 T-cell count of 200 cells/mm<sup>3</sup> or less or an AIDS-defining condition</li> </ul><li>(2) Most common AIDS-defining infections</li><ul> <li><i>Pneumocystis jiroveci</i> pneumonia (<span>[[Fig. 3-3|Figure 3-3]]</span>), systemic candidiasis</li> </ul><li>(3) AIDS-defining malignancies
<blockquote style="color: blue; ">CMV: most common cause of blindness in AIDS</blockquote></li><ul> <li>Kaposi's sarcoma (<span>[[Fig. 3-4|Figure 3-4]]</span>), Burkitt's lymphoma (EBV), primary CNS lymphoma (EBV)</li> </ul><li>(4) Causes of death
<blockquote style="color: blue; ">Death in AIDS: disseminated infection</blockquote></li><ul> <li>Disseminated infections (cytomegalovirus, <i>Mycobacterium avium</i> complex)</li> </ul> </ul><li>Immunologic abnormalities</li><ul> <li>(1) Lymphopenia (low CD4 T-cell count)</li><li>(2) Cutaneous anergy (defect in cell-mediated immunity)</li><li>(3) Hypergammaglobulinemia (due to polyclonal B-cell stimulation by EBV)</li><li>(4) CD4:CD8 ratio < 1</li> </ul><li>CD4 count and risk for certain diseases</li><ul> <li>(1) 700 to 1500: normal</li><li>(2) 200 to 500: oral thrush, herpes zoster (shingles), hairy leukoplakia</li><li>(3) 100 to 200: <i>Pneumocystis jiroveci</i> pneumonia, dementia</li><li>(4) Below 100: toxoplasmosis, cryptococcosis, cryptosporidiosis</li><li>(5) Below 50: CMV retinitis, <i>Mycobacterium avium</i> complex, progressive multifocal leukoencephalopathy, primary central nervous system lymphoma</li> </ul> </ol><li>Pregnant women with AIDS</li><ul> <li>Treatment with a reverse transcriptase inhibitor reduces transmission to newborns to less than 8%.</li> </ul> </ol>
</div></html>
<html><a name="HC003033"></a> <br><a name="P003031"></a><div class="PA" style="color: black; "><ol type="1"> <li>Overview</li><ol type="a"> <li>Synthesized in the liver</li><li>Augment natural host immune defense</li><ul> <li>Acute phase reactant (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>)</li> </ul><li>Circulate as inactive proteins</li><ul> <li>(1) Activated by IgM, IgG-antigen complexes, endotoxin</li><ul> <li>Complement: only cleavage products are functional</li> </ul><li>(2) Only complement cleavage products are functional.</li> </ul><li>Functions complement cleavage products</li><ul> <li>(1) C3a, C5a (anaphylatoxins)
<blockquote style="color: blue; ">C3a, C5a: anaphylatoxins</blockquote></li><ul> <li>Stimulate mast cell release of histamine</li> </ul><li>(2) C3b
<blockquote style="color: blue; ">C3b: opsonization</blockquote></li><ul> <li>Opsonization</li> </ul><li>(3) C5a
<blockquote style="color: blue; ">C5a: activate neutrophil adhesion molecules; chemotaxis</blockquote></li><ul> <li>(a) Activation of neutrophil adhesion molecules</li><li>(b) Neutrophil chemotaxis</li> </ul><li>(4) C5-C9 (membrane attack complex, MAC)
<blockquote style="color: blue; ">C5-C9: cell lysis</blockquote></li><ul> <li>Cell lysis</li> </ul> </ul> </ol><li>Complement pathways (<span>[[Fig. 3-5|Figure 3-5]]</span>)</li><ol type="a"> <li>Classic pathway</li><ul> <li>(1) Contains complement components C1, C4, C2</li><li>(2) C1 esterase inhibitor</li><ul> <li>(a) Inactivates the protease activity of C1</li><ul> <li>Protease normally cleaves C2 and C4 to produce C4b2b complex (C3 convertase)</li> </ul><li>(b) Inhibitor is deficient in hereditary angioedema
<blockquote style="color: blue; ">Hereditary angioedema: deficiency C1 esterase inhibitor</blockquote></li> </ul> </ul><li>Alternative pathway</li><ul> <li>Contains complement components factor B, properdin, factor D</li> </ul><li>Membrane attack complex (C5-C9)</li><ul> <li>Final common pathway for both the classic and alternative pathways.</li> </ul><li>Decay accelerating factor (DAF)</li><ul> <li>(1) Present on cell membranes</li><li>(2) Enhances degradation of C3 convertase and C5 convertase</li><li>(3) Protects the cell against MAC destruction</li><li>(4) Deficient in paroxysmal nocturnal hemoglobinuria (PNH) (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>)
<blockquote style="color: blue; ">DAF: deficient in PNH</blockquote></li> </ul> </ol><li>Testing of the complement system</li><ol type="a"> <li>Total hemolytic complement assay (CH<sub>50</sub>)</li><ul> <li>Tests functional ability of both complement systems</li> </ul><li>Tests indicating activation of classic system
<blockquote style="color: blue; ">Classical pathway activation: decreased C4, C3; normal factor B</blockquote></li><ul> <li>(1) Decreased C4, C3</li><li>(2) Normal factor B</li> </ul><li>Tests indicating activation of alternative system
<blockquote style="color: blue; ">Alternative pathway activation: decreased factor B, C3; normal C4</blockquote></li><ul> <li>(1) Decreased factor B, C3</li><li>(2) Normal C4</li> </ul><li>Tests indicating activation of both systems</li><ul> <li>Decreased C4, factor B, C3</li> </ul> </ol><li>Summary of complement disorders (<span>[[Table 3-8|Table 3-8. COMPLEMENT DISORDERS]]</span>)</li> </ol>
</div></html>
![[3.VI.A.Risk factors for immune disorders]]
<<tiddler [[3.VI.A.Risk factors for immune disorders]]>>
![[3.VI.B.Congenital immunodeficiency disorders (Table 3-5)]]
<<tiddler [[3.VI.B.Congenital immunodeficiency disorders (Table 3-5)]]>>
![[3.VI.C.Acquired immunodeficiency syndrome]]
<<tiddler [[3.VI.C.Acquired immunodeficiency syndrome]]>>
![[3.VI.D.Complement system disorders]]
<<tiddler [[3.VI.D.Complement system disorders]]>>
<html><a name="HC003035"></a> <br><a name="P003035"></a><div class="PA" style="color: black; "><ol type="1"> <li>Fibrillar protein that forms deposits in interstitial tissue, resulting in organ dysfunction</li><li>Characteristics</li><ol type="a"> <li>Linear, nonbranching filaments in a β-pleated sheet</li><li>Apple green-colored birefringence in polarized light with Congo red stain of tissue (<span>[[Fig. 3-6|Figure 3-6]]</span>)
<blockquote style="color: blue; ">Amyloid: apple green birefringence in polarized light</blockquote></li><li>Eosinophilic staining with H&E (hematoxylin and eosin) stain (<span>[[Fig. 3-7|Figure 3-7]]</span>)</li><li>Derived from various proteins</li> </ol><li>Major types of amyloid proteins</li><ol type="a"> <li>Amyloid light (AL) chain</li><ul> <li>Derived from light chains (e.g., Bence Jones protein)</li> </ul><li>Amyloid-associated (AA)</li><ul> <li>Derived from serum-associated amyloid, an acute phase reactant (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>)
<blockquote style="color: blue; ">β-Amyloid is associated with Alzheimer's disease in Down syndrome.</blockquote></li> </ul><li>β-Amyloid (Aβ)</li><ul> <li>Derived from amyloid precursor protein (protein product of chromosome 21)</li> </ul> </ol> </ol>
</div></html>
![[3.VII.A.Amyloid]]
<<tiddler [[3.VII.A.Amyloid]]>>
![[3.VII.B.Types of amyloidosis (Table 3-9)]]
<<tiddler [[3.VII.B.Types of amyloidosis (Table 3-9)]]>>
![[3.VII.C.Pathogenesis]]
<<tiddler [[3.VII.C.Pathogenesis]]>>
![[3.VII.D.Techniques used to diagnose amyloidosis]]
<<tiddler [[3.VII.D.Techniques used to diagnose amyloidosis]]>>
<html><a name="HC003036"></a><span>[[Table 3-9|Table 3-9. COMMON TYPES OF AMYLOIDOSIS AND ASSOCIATED CLINICAL FINDINGS]]</span> <br> <br><a name="P003036"></a><div class="PA" style="color: black; "><ol type="1"> <li>Systemic</li><ol type="a"> <li>Similar tissue involvement in both primary and secondary types</li><li>Primary amyloidosis</li><ul> <li>(1) AL amyloid disposition</li><li>(2) Associated with multiple myeloma (30% of cases)</li> </ul><li>Secondary (reactive)</li><ul> <li>(1) AA amyloid</li><li>(2) Associated with chronic inflammation (e.g., rheumatoid arthritis, tuberculosis)</li> </ul> </ol><li>Localized</li><ol type="a"> <li>Confined to a single organ (e.g., brain)</li><li>Alzheimer's disease</li><ul> <li>(1) Aβ</li><li>(2) Most common cause of dementia</li> </ul> </ol><li>Hereditary</li><ul> <li>Autosomal recessive disorder involving AA amyloid (e.g., familial Mediterranean fever)</li> </ul> </ol>
</div></html>
<html><a name="HC003037"></a> <br><a name="P003037"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Amyloid: abnormal folding of protein</blockquote>
<ul> <li>Abnormal folding of normal or mutant proteins</li> </ul>
</div></html>
<html><a name="HC003038"></a> <br><a name="P003038"></a><div class="PA" style="color: black; "><ol type="1"> <li>Immunoelectrophoresis (to detect light chains) in primary amyloidosis</li><li>Tissue biopsy (e.g., adipose, rectum)</li> </ol>
</div></html>
<html><a name="HC004002"></a> <br><a name="P004001"></a><div class="PA" style="color: black; "><ol type="1"> <li>Total body water (TBW) is ∼60% of the body weight in kg (<span>[[Fig. 4-1|Figure 4-1]]</span>).</li><ol type="a"> <li>TBW distribution</li><ul> <li>(1) Intracellular fluid (ICF) compartment</li><ul> <li>Equals ∼40% of body weight in kg</li> </ul><li>(2) Extracellular fluid (ECF) compartment</li><ul> <li>Equals ∼20% of body weight in kg</li> </ul><li>(3) ECF is subdivided into the interstitial and vascular compartments.
<blockquote style="color: blue; ">Compartment sizes: ICF > ECF; interstitial > vascular</blockquote></li> </ul><li>Sodium (Na<sup>+</sup>) is the major ECF cation.</li><ul> <li>Chloride (Cl<sup>-</sup>) major anion</li> </ul><li>Potassium (K<sup>+</sup>) is the major ICF cation.</li><ul> <li>Phosphate (PO<sub>4</sub><sup>2-</sup>) major cation.
<blockquote style="color: blue; ">Na<sup>+</sup>, K<sup>+</sup>: major ECF and ICF cations, respectively</blockquote></li> </ul> </ol><li>Plasma osmolality (POsm)</li><ol type="a"> <li>Osmolality is the number of solutes in plasma (i.e., tonicity of ECF).</li><ul> <li>(1) Isotonic state = normal POsm</li><li>(2) Hypotonic state = decreased POsm</li><li>(3) Hypertonic state = increased POsm</li> </ul><li>POsm = 2 (serum Na<sup>+</sup>) + serum glucose/18 + serum blood urea nitrogen (BUN)/2.8 = 275-295 mOsm/kg</li><ul> <li>POsm roughly correlates with the serum Na<sup>+</sup> concentration.</li> </ul><li>Urea diffuses freely between ECF and ICF.</li><ul> <li>(1) Nephrologists frequently use the term effective osmolality (EOsm).</li><ul> <li>Excludes urea from the calculation, because it does not affect the osmotic gradient
<blockquote style="color: blue; ">EOsm = 2 (serum Na<sup>+</sup>) + serum glucose/18</blockquote></li> </ul><li>(2) EOsm = 2 (serum Na<sup>+</sup>) + serum glucose/18</li> </ul> </ol><li>Na<sup>+</sup> and glucose are limited to the ECF (impermeant solutes).</li><ol type="a"> <li>Changes in their concentration produce an osmotic gradient.</li><ul> <li>(1) Water shifts between the ECF and ICF compartments by osmosis.
<blockquote style="color: blue; ">Osmosis: H<sub>2</sub>O moves between ECF and ICF; controlled by serum Na<sup>+</sup></blockquote></li><li>(2) Water moves from a low to a high solute concentration.</li><li>(3) Water shifts do not occur with alterations in urea concentration.</li><ul> <li>Urea is a permeant solute and diffuses between the ECF and ICF.</li> </ul> </ul><li>Hyponatremia (decreased POsm) causes water to shift from ECF to ICF (<span>[[Fig. 4-2A|Figure 4-2]]</span>).</li><li>Hypernatremia and hyperglycemia (increased POsm) cause water to shift from ICF to ECF (<span>[[Fig. 4-2B|Figure 4-2]]</span>).</li> </ol> </ol>
</div></html>
<html><a name="HC004003"></a> <br><a name="PB004001"></a><div class="BB" style="color: rgb(47, 79, 79); ">Fluid movement across a capillary/venule wall into the interstitial space is driven by Starling pressures (not osmosis). The net direction of fluid movement depends on which Starling pressure is dominant. An increase in plasma hydrostatic pressure or a decrease in plasma oncotic pressure (i.e., serum albumin) causes fluid to diffuse out of capillaries and venules and into the interstitial space, resulting in dependent pitting edema and body cavity effusions.</div><a name="PB004002"></a><div class="BB" style="color: rgb(47, 79, 79); ">Normal (isotonic) saline (0.9%) approximates plasma tonicity (POsm). It is infused in patients to maintain the blood pressure when there is a significant loss of sodium-containing fluid (e.g., blood loss, diarrhea, sweat). As expected, some of the normal saline enters the interstitial compartment and some remains in the vascular compartment, the latter being responsible for the increase in blood pressure. Other solutions that are used that are more expensive include Ringer's lactate and 5% albumin (remains in the vascular compartment).</div><a name="PB004003"></a><div class="BB" style="color: rgb(47, 79, 79); ">In an alcoholic, rapid intravenous fluid correction of hyponatremia with saline may result in central pontine myelinolysis (see <span>[[Fig. 25-28|Figure 25-28]]</span>), an irreversible demyelinating disorder. However, as a general rule, all intravenous replacement of sodium-containing fluids should be given slowly over the first 24 hours regardless of the cause of the underlying serum sodium imbalance.</div><a name="PB004004"></a><div class="BB" style="color: rgb(47, 79, 79); ">In these pitting edema states, the cardiac output is decreased, which causes the release of catecholamines, activation of the renin-angiotensin-aldosterone system, stimulation of ADH release, and increased renal retention of Na<sup>+</sup>. The kidney reabsorbs a slightly hypotonic, Na<sup>+</sup>-containing fluid (↑TBNa<sup>+</sup>/↑↑TBW). Because these pitting edema states have alterations in Starling pressures, the Na<sup>+</sup>-containing fluid is redirected into the interstitial space, causing pitting edema and body cavity effusions. Unfortunately, the cardiac output remains decreased, until the cause of the decreased cardiac output is corrected.</div><a name="P004002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Serum Na<sup>+</sup> concentration (mEq/L) reflects the ratio of total body Na<sup>+</sup> (TBNa<sup>+</sup>) to total body water (TBW).</li><ol type="a"> <li>Serum Na<sup>+</sup> ∼ TBNa<sup>+</sup>/TBW
<blockquote style="color: blue; ">Serum Na<sup>+</sup> ∼ TBNa<sup>+</sup>/TBW</blockquote></li><ul> <li>TBNa<sup>+</sup> is the sum total of all the ECF Na<sup>+</sup> (vascular space and interstitial space); unlike serum Na<sup>+</sup>, which is the amount of Na<sup>+</sup> in a liter of serum/plasma in the vascular compartment.</li> </ul><li>Evaluation of TBNa<sup>+</sup> status</li><ul> <li>(1) Decreased TBNa<sup>+</sup> produces signs of volume depletion.</li><ul> <li>(a) Dry mucous membranes (<span>[[Fig. 4-3|Figure 4-3]]</span>)</li><li>(b) Decreased skin turgor (i.e., skin tenting when the skin is pinched)</li><li>(c) Drop in blood pressure and increase in pulse when sitting up from a supine position (i.e., positive tilt test)
<blockquote style="color: blue; ">↓ TBNa<sup>+</sup>: signs of volume depletion</blockquote></li> </ul><li>(2) Increased TBNa<sup>+</sup> may produce body cavity effusions (e.g., ascites) and dependent pitting edema (<span>[[Fig. 4-4|Figure 4-4]]</span>).</li><ul> <li>(a) Dependent pitting edema is due to an excess of Na<sup>+</sup>-containing fluid in the interstitial space (>2-3 liters).</li><ul> <li>Due to the low protein content in edema fluid, fluid obeys the law of gravity and moves to the most dependent portion of the body (e.g., ankles, if the person is standing).</li> </ul><li>(b) An alteration in Starling pressures must be present to produce pitting edema and body effusions.
<blockquote style="color: blue; ">↑↑ TBNa<sup>+</sup>: pitting edema, body cavity effusions</blockquote>
<blockquote style="color: blue; ">Starling pressure alterations: control water movement in ECF compartment</blockquote></li> </ul><li>(3) An increase in TBNa<sup>+</sup> increases plasma hydrostatic pressure.</li><ul> <li>Due to an increase in plasma volume</li> </ul><li>(4) An increase in TBNa<sup>+</sup> increases the weight of the patient.</li><ul> <li>The most common cause of an increase in weight in a hospitalized patient is an increase in TBNa<sup>+</sup>.
<blockquote style="color: blue; ">↑ Weight of patient in hospital: ↑TBNa<sup>+</sup></blockquote></li> </ul><li>(5) Normal TBNa<sup>+</sup> is associated with normal skin turgor and hydration.</li> </ul> </ol><li>Isotonic fluid disorders (<span>[[Table 4-1|Table 4-1. ISOTONIC AND HYPOTONIC DISORDERS]]</span>)</li><ol type="a"> <li>Isotonic loss of fluid
<blockquote style="color: blue; ">Isotonic loss: ↓TBNa<sup>+</sup>/↓TBW; loss whole blood, secretory diarrhea (e.g., cholera)</blockquote></li><ul> <li>(1) Isotonic net loss of Na<sup>+</sup> and H<sub>2</sub>O (↓TBNa<sup>+</sup>/↓TBW)</li><li>(2) POsm and serum Na<sup>+</sup> are normal.</li><ul> <li>The arrows represent the magnitude of change in TBNa<sup>+</sup> and TBW.</li> </ul><li>(3) There is no osmotic gradient or fluid shift between ECF and ICF.
<blockquote style="color: blue; ">Isotonic gain: ↑TBNa<sup>+</sup>/↑TBW; excessive infusion isotonic saline</blockquote></li><ul> <li>ECF volume contracts; however, the ICF volume remains normal.</li> </ul><li>(4) Signs of volume depletion are present.</li><li>(5) Examples include adult diarrhea, loss of whole blood.</li> </ul><li>Isotonic gain of fluid</li><ul> <li>(1) Isotonic net gain of Na<sup>+</sup> and H<sub>2</sub>O (↑TBNa<sup>+</sup>/↑TBW)</li><li>(2) POsm and serum Na<sup>+</sup> are normal.</li><li>(3) There is no osmotic gradient or fluid shift between ECF and ICF.</li><ul> <li>ECF volume expands; however, the ICF volume remains normal.</li> </ul><li>(4) Pitting edema and body cavity effusions may be present.</li><li>(5) Example is excessive infusion of isotonic saline.
<blockquote style="color: blue; ">Isotonic loss or gain: serum Na<sup>+</sup> normal</blockquote></li> </ul> </ol><li>Hypotonic fluid disorders (see <span>[[Table 4-1|Table 4-1. ISOTONIC AND HYPOTONIC DISORDERS]]</span>)</li><ol type="a"> <li>Hyponatremia (decreased POsm) is always present.
<blockquote style="color: blue; ">Hypotonic disorders: hyponatremia always present; ICF expansion</blockquote></li><ul> <li>(1) Osmotic gradient is present.</li><li>(2) Water shifts to the ICF compartment (expands).</li> </ul><li>Hypertonic loss of Na<sup>+</sup>
<blockquote style="color: blue; ">Gain in fluid: ECF always expands</blockquote></li><ul> <li>(1) Net loss of Na<sup>+</sup> in excess of water (↓↓TBNa<sup>+</sup>/↓TBW)</li><li>(2) POsm and serum Na<sup>+</sup> are decreased
<blockquote style="color: blue; ">Loss in fluid: ECF always contracts</blockquote></li><li>(3) ECF volume contracts and ICF volume expands.</li><li>(4) Signs of volume depletion are present.</li><li>(5) Examples-causes of increased renal loss of Na<sup>+</sup> include loop diuretic, Addison's disease, 21-hydroxylase deficiency
<blockquote style="color: blue; ">Hypertonic loss: ↓↓TBNa<sup>+</sup>/↓TBW; loop diuretic, Addison's disease, 21-hydroxylase deficiency</blockquote></li> </ul><li>Gain of pure water
<blockquote style="color: blue; ">Central pontine myelinolysis: rapid correction of hyponatremia with saline</blockquote></li><ul> <li>(1) Net gain in only water (TBNa<sup>+</sup>/↑↑TBW)</li><li>(2) Decreased POsm and serum Na<sup>+</sup></li><li>(3) Expansion of ECF and ICF volumes</li><li>(4) Normal skin turgor
<blockquote style="color: blue; ">Hypotonic gain of water: TBNa<sup>+</sup>/↑↑TBW; SIADH</blockquote></li><li>(5) Examples-syndrome of inappropriate secretion of antidiuretic hormone (syndrome of inappropriate antidiuretic hormone [SIADH], e.g., small cell carcinoma of the lung), compulsive water drinking</li> </ul><li>Hypotonic gain of Na<sup>+</sup></li><ul> <li>(1) Net gain in H<sub>2</sub>O in excess of Na<sup>+</sup> (↑TBNa<sup>+</sup>/↑↑TBW)</li><li>(2) Decreased POsm and serum Na<sup>+</sup></li><li>(3) Expansion of the ECF and ICF volumes</li><li>(4) Caused by pitting edema states with Starling pressure alterations</li><ul> <li>(a) Right-sided heart failure with increase in venous hydrostatic pressure</li><li>(b) Cirrhosis and nephrotic syndrome with decrease in plasma oncotic pressure
<blockquote style="color: blue; ">Hypotonic gain water + Na<sup>+</sup>: ↑TBNa<sup>+</sup>/↑↑TBW</blockquote></li> </ul> </ul> </ol><li>Hypertonic fluid disorders (<span>[[Table 4-2|Table 4-2. HYPERTONIC DISORDERS]]</span>)
<blockquote style="color: blue; ">Pitting edema states: right-side heart failure, cirrhosis, nephrotic syndrome; cardiac output decreased</blockquote>
<blockquote style="color: blue; ">Hypertonic disorder: hypernatremia or hyperglycemia; ICF contraction</blockquote></li><ol type="a"> <li>Increased POsm is most often due to hypernatremia or hyperglycemia.</li><ul> <li>(1) Osmotic gradient is present.</li><li>(2) Water shifts from the ICF (contracts) to the ECF.</li> </ul><li>Hypotonic loss of Na<sup>+</sup></li><ul> <li>(1) Net loss of H<sub>2</sub>O in excess of Na<sup>+</sup> (↓TBNa<sup>+</sup>/↓↓TBW)</li><li>(2) POsm and serum Na<sup>+</sup> increased</li><li>(3) Contraction of the ECF and ICF volumes</li><li>(4) Signs of volume depletion
<blockquote style="color: blue; ">Hypotonic loss Na<sup>+</sup> + water: ↓TBNa<sup>+</sup>/↓↓TBW; osmotic diuresis, sweating</blockquote></li><li>(5) Examples-sweating, osmotic diuresis (e.g., glucosuria)</li> </ul><li>Loss of pure water</li><ul> <li>(1) Net loss of only H<sub>2</sub>O (TBNa<sup>+</sup>/↓↓TBW)</li><li>(2) POsm and serum Na<sup>+</sup> increased</li><li>(3) Contraction of the ECF and ICF volumes</li><ul> <li>ECF contraction is mild, because there has been no loss of Na<sup>+</sup>.</li> </ul><li>(4) Normal skin turgor</li><li>(5) Examples
<blockquote style="color: blue; ">Hypotonic loss of water: TBNa<sup>+</sup>/↓↓TBW; diabetes insipidus; insensible water loss</blockquote></li><ul> <li>(a) Diabetes insipidus, due to loss of antidiuretic hormone (ADH) or refractoriness to ADH</li><li>(b) Insensible water loss (e.g., fever)</li><ul> <li>Water evaporates from the warm skin surface.</li> </ul> </ul> </ul><li>Hypertonic gain of Na<sup>+</sup></li><ul> <li>(1) Net gain in Na<sup>+</sup> in excess of H<sub>2</sub>O (↑↑TBNa<sup>+</sup>/↑TBW)</li><li>(2) POsm and serum Na<sup>+</sup> increase.</li><li>(3) ECF volume expands and ICF volume contracts.</li><li>(4) Pitting edema and body cavity effusions may be present.
<blockquote style="color: blue; ">Hypertonic gain: ↑↑TBNa<sup>+</sup>/↑TBW; excess NaHCO<sub>3</sub>, infusion Na<sup>+</sup>- containing antibiotic</blockquote></li><li>(5) Examples include infusion of NaHCO<sub>3</sub> or Na<sup>+</sup>-containing antibiotics.</li> </ul><li>Hypertonic state due to hyperglycemia</li><ul> <li>Examples-diabetic ketoacidosis (DKA), hyperosmolar nonketotic coma</li> </ul><ul> <li>(1) Water shifts from the ICF to the ECF compartment.</li><ul> <li>(a) Dilutional effect on serum Na<sup>+</sup> causes hyponatremia.</li><li>(b) Increased POsm (due to hyperglycemia) and hyponatremia (dilutional)</li><li>(c) Water does not remain in the ECF, because glucose in urine acts as an osmotic diuretic causing loss of water and Na<sup>+</sup>.</li> </ul><li>(2) Signs of volume depletion
<blockquote style="color: blue; ">Diabetic ketoacidosis: hypertonic state with dilutional hyponatremia; osmotic diuresis</blockquote></li><ul> <li>Glucosuria produces a hypotonic loss of water and Na<sup>+</sup> (osmotic diuresis), causing signs of volume depletion.</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC004004"></a><span>[[Box 4-1|BOX 4-1 VOLUME CONTROL]]</span> <br> <br> </html>
<html><a name="HC004005"></a> <br><a name="PB004005"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Carbonic anhydrase inhibitors</b> (e.g., acetazolamide) lower the renal threshold for reclaiming HCO<sub>3</sub><sup>-</sup>. HCO<sub>3</sub><sup>-</sup> combines with Na<sup>+</sup> to form NaHCO<sub>3</sub>, which is excreted, hence acting as a proximal tubule diuretic. Loss of HCO<sub>3</sub><sup>-</sup> produces metabolic acidosis (see later).</div><a name="PB004006"></a><div class="BB" style="color: rgb(47, 79, 79); ">In <b>heavy metal poisoning</b> with lead or mercury, the proximal tubule cells undergo coagulation necrosis, which produces a nephrotoxic acute tubular necrosis (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>). All of the normal proximal renal tubule functions are destroyed resulting in a loss of sodium (hyponatremia), glucose (hypoglycemia), uric acid (hypouricemia), phosphorus (hypophosphatemia), amino acids, bicarbonate (type II proximal renal tubular acidosis), and urea in the urine. This is called the Fanconi syndrome.</div><a name="PB004007"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Loop diuretics</b> (e.g., furosemide) are the mainstay for the treatment of congestive heart failure and hypercalcemia. They decrease TBNa<sup>+</sup> and TBW (see above) and also decrease reabsorption of Ca<sup>2+</sup> by the Na<sup>+</sup>-K<sup>+</sup>-2 Cl<sup>-</sup> cotransporter. The drug attaches to the Cl<sup>-</sup> binding site of the cotransporter, which not only inhibits reabsorption of Na<sup>+</sup>, K<sup>+</sup>, and Cl<sup>-</sup> but also impairs the generation of fH<sub>2</sub>O. The electrolytes are lost in the urine as obligated water. Because the normal dilution process is impaired, patients must be warned against consuming excess amounts of water. Loop diuretics also result in a hypertonic loss of Na<sup>+</sup> in the urine (see above) which, along with impaired dilution, may produce hyponatremia. Additional electrolyte abnormalities include hypokalemia and metabolic alkalosis (see later).</div><a name="PB004008"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Thiazides</b> in addition to being a diuretic are the mainstay for the treatment of hypertension in blacks and the elderly. Both patient populations have renal retention of Na<sup>+</sup> as the primary cause of the hypertension (refer to <span macro="tag [[08 Neoplasia]] [[Chapter 8]]"></span>). Thiazides are also used in the treatment of hypercalciuria in Ca<sup>2+</sup> renal stone formers (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>). The drug attaches to the Cl<sup>-</sup> site and inhibits Na<sup>+</sup> and Cl<sup>-</sup> reabsorption. This leaves the Na<sup>+</sup> channel open for Ca<sup>2+</sup> reabsorption.</div><a name="PB004009"></a><div class="BB" style="color: rgb(47, 79, 79); ">Hyponatremia may occur due to a hypertonic loss of sodium (see earlier) in the urine. Additional electrolyte abnormalities include hypokalemia and metabolic alkalosis (see later). Hypercalcemia may also be a complication; however, this is uncommon and is more likely to occur if the patient has primary hyperparathyroidism with an increase in PTH.</div><a name="PB004010"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Amiloride</b> and <b>triamterene</b> are diuretics with K<sup>+</sup>-sparing effect. They bind to the luminal membrane Na<sup>+</sup> channels, hence inhibiting Na<sup>+</sup> reabsorption and K<sup>+</sup> excretion.</div><a name="PB004011"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Spironolactone</b> is a diuretic with a K<sup>+</sup>-sparing effect. It inhibits aldosterone, which results in a loss of Na<sup>+</sup> in the urine (see <span>[[Fig. 4-8A|Figure 4-8]]</span>) and retention of K<sup>+</sup> in the blood (K<sup>+</sup>-sparer). Hyperkalemia may occur in some cases. H<sup>+</sup> is retained, which produces metabolic acidosis in some cases (see <span>[[Fig. 4-9|Figure 4-9]]</span>).</div><a name="PB004012"></a><div class="BB" style="color: rgb(47, 79, 79); ">An <b>angiotensin converting enzyme (ACE) inhibitor</b> is important in the treatment of congestive heart failure. Inhibition of the enzyme causes a decrease in angiotensin II (ATII) and aldosterone. ATII is normally a vasoconstrictor of peripheral resistance arterioles, which increases afterload (resistance the heart must contract against). Aldosterone normally reabsorbs sodium and increases preload (volume in the left ventricle). Therefore, an ACE inhibitor decreases both afterload and preload. The inhibition of aldosterone is short-lived and is frequently counterbalanced by the use of spironolactone.</div><a name="P004003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Proximal renal tubule</li><ol type="a"> <li>Primary site for Na<sup>+</sup> reabsorption
<blockquote style="color: blue; ">Proximal tubule: reabsorb Na<sup>+</sup>, reclaim HCO<sub>3</sub><sup>-</sup></blockquote></li><ul> <li>(1) Na<sup>+</sup> reabsorption is increased when cardiac output is decreased.</li><ul> <li>(a) ↓ EABV→ ↑ FF → P<sub>O</sub> > P<sub>H</sub>
<blockquote style="color: blue; ">↓ EABV → ↓ FF → P<sub>O</sub> > P<sub>H</sub></blockquote></li><li>(b) Examples-congestive heart failure, cirrhosis, hypovolemia
<blockquote style="color: blue; ">↑ EABV → ↓ FF → P<sub>H</sub> > P<sub>O</sub></blockquote></li> </ul><li>(2) Na<sup>+</sup> reabsorption is decreased when cardiac output is increased.</li><ul> <li>(a) ↑EABV→↓ FF → P<sub>H</sub> > P<sub>O</sub></li><li>(b) Examples-mineralocorticoid excess, isotonic gain in fluid</li> </ul> </ul><li>Primary site for reclamation of bicarbonate (HCO<sub>3</sub><sup>-</sup>; <span>[[Fig. 4-5|Figure 4-5]]</span>)</li><ul> <li>Mechanism for reabsorbing some of the filtered HCO<sub>3</sub><sup>-</sup> back into the blood</li> </ul><ul> <li>(1) Hydrogen ions (H<sup>+</sup>) in tubular cells are exchanged for Na<sup>+</sup> in the urine.</li><li>(2) H<sup>+</sup> combines with filtered HCO<sub>3</sub><sup>-</sup> to form H<sub>2</sub>CO<sub>3</sub> in the brush border of the proximal tubules.</li><li>(3) Carbonic anhydrase (c.a.) dissociates H<sub>2</sub>CO<sub>3</sub> to H<sub>2</sub>O and CO<sub>2</sub></li><ul> <li>CO<sub>2</sub> and H<sub>2</sub>O are reabsorbed into proximal renal tubular cells.</li> </ul><li>(4) H<sub>2</sub>CO<sub>3</sub> is re-formed in the proximal renal tubular cells.</li><ul> <li>H<sub>2</sub>CO<sub>3</sub> dissociates into H<sup>+</sup> and HCO<sub>3</sub><sup>-</sup>.</li> </ul><li>(5) HCO<sub>3</sub><sup>-</sup> is reabsorbed into the blood.</li><li>(6) An Na<sup>+</sup>/K<sup>+</sup>-ATPase pump moves Na<sup>+</sup> into the blood.</li> </ul><li>Clinical effect of lowering renal threshold for reclaiming HCO<sub>3</sub><sup>-</sup></li><ul> <li>(1) Example-normal threshold is lowered from the normal of 24 mEq/L to 15 mEq/L.</li><li>(2) This results in loss of more of the filtered HCO<sub>3</sub><sup>-</sup> than normal.</li><ul> <li>(a) Urine pH > 5.5 (alkalinizing effect of increased HCO<sub>3</sub><sup>-</sup>)</li><li>(b) Urine loss of HCO<sub>3</sub><sup>-</sup> occurs until serum HCO<sub>3</sub><sup>-</sup> matches the renal threshold.</li> </ul> </ul><li>Clinical effect of raising renal threshold for reclaiming HCO<sub>3</sub><sup>-</sup>
<blockquote style="color: blue; ">Carbonic anhydrase inhibitor: causes proximal renal tubular acidosis</blockquote></li><ul> <li>(1) Example-volume depletion associated with vomiting</li><li>(2) Increased threshold means that proportionately more of the filtered HCO<sub>3</sub><sup>-</sup> is reclaimed.</li><ul> <li>Increased reclamation of HCO<sub>3</sub><sup>-</sup> is the most important factor contributing to the increase in serum HCO<sub>3</sub><sup>-</sup> that defines metabolic alkalosis (see later).</li> </ul> </ul> </ol><li>Thick ascending limb (TAL; medullary segment)
<blockquote style="color: blue; ">Heavy metal poisoning: produces Fanconi syndrome</blockquote></li><ol type="a"> <li>Primary function is to generate free water (fH<sub>2</sub>O)</li><ul> <li>Secondary function is to reabsorb calcium (Ca<sup>2+</sup>)</li> </ul><li>Generation of fH<sub>2</sub>O primarily occurs in the active Na<sup>+</sup>-K<sup>+</sup>-2 Cl<sup>-</sup> cotransporter (<span>[[Fig. 4-6|Figure 4-6]]</span>)</li><li>Water proximal to the cotransporter is obligated (o).</li><ul> <li>(1) Water is normally bound to Na<sup>+</sup> (oNa<sup>+</sup>), K<sup>+</sup> (oK<sup>+</sup>), and Cl<sup>-</sup> (oCl<sup>-</sup>).</li><li>(2) Obligated water must accompany every Na<sup>+</sup>, K<sup>+</sup>, or Cl<sup>-</sup> excreted in urine.
<blockquote style="color: blue; ">Na<sup>+</sup>-K<sup>+</sup>-2 Cl- cotransporter: generates free water</blockquote></li><li>(3) Obligated water cannot be reabsorbed by ADH, only fH<sub>2</sub>O.</li> </ul><li>Cotransporter separates oH<sub>2</sub>O from Na<sup>+</sup>, K<sup>+</sup>, and Cl<sup>-</sup>.</li><ul> <li>(1) Water left behind in the urine is fH<sub>2</sub>O.</li><ul> <li>(a) fH<sub>2</sub>O is entirely free of electrolytes.</li><li>(b) Reabsorption of fH<sub>2</sub>O concentrates the urine.</li><li>(c) Loss of fH<sub>2</sub>O in the urine dilutes urine.</li> </ul><li>(2) Urine Osm (UOsm) is ∼150 mOsm/kg distal to the TAL medullary segment.</li> </ul><li>A Na<sup>+</sup>/K<sup>+</sup>-ATPase pump moves reabsorbed Na<sup>+</sup> into the interstitium.</li><li>Reabsorbed Cl<sup>-</sup> and K<sup>+</sup> diffuse through channels into the interstitium.</li><li>Ca<sup>2+</sup> is also reabsorbed by the cotransporter.</li><li>Cl<sup>-</sup> binding site in Na<sup>+</sup>-K<sup>+</sup>-2 Cl<sup>-</sup> cotransporter is inhibited by loop diuretics.
<blockquote style="color: blue; ">Cl<sup>-</sup> binding site in Na<sup>+</sup>-K<sup>+</sup>-2 Cl<sup>-</sup> cotransporter: inhibited by loop diuretics Loop diuretic: hyponatremia, hypokalemia, metabolic alkalosis</blockquote></li> </ol><li>Na<sup>+</sup>-Cl<sup>-</sup> cotransporter in the early distal tubule</li><ol type="a"> <li>Function is to reabsorb Na<sup>+</sup> and Ca<sup>2+</sup>.</li><li>Na<sup>+</sup> and Ca<sup>2+</sup> share the same site for reabsorption (<span>[[Fig. 4-7|Figure 4-7]]</span>).</li><ul> <li>Parathyroid hormone (PTH)-enhanced Ca<sup>2+</sup> reabsorption</li> </ul><li>Na<sup>+</sup>/K<sup>+</sup>-ATPase pump moves Na<sup>+</sup> into the blood.</li><ul> <li>Cl<sup>-</sup> diffuses through a channel into the blood.</li> </ul><li>Thiazides inhibit the Cl<sup>-</sup> site in the Na<sup>+</sup>-Cl<sup>-</sup> cotransporter.
<blockquote style="color: blue; ">Thiazides: inhibit Cl<sup>-</sup> site in Na<sup>+</sup>-Cl<sup>-</sup> cotransporter</blockquote>
<blockquote style="color: blue; ">Thiazide diuretic: hyponatremia, hypokalemia, metabolic alkalosis, hypercalcemia</blockquote></li> </ol><li>Na<sup>+</sup> and K<sup>+</sup> channels in the late distal tubule and collecting ducts</li><ol type="a"> <li>Aldosterone-enhanced pump functions to reabsorb Na<sup>+</sup> and excrete K<sup>+</sup>.</li><li>Na<sup>+</sup> diffuses into the cell (<span>[[Fig. 4-8A|Figure 4-8]]</span>).</li><li>K<sup>+</sup> diffuses out of the cell to maintain electroneutrality.</li><ul> <li>Primary site for K<sup>+</sup> excretion</li> </ul><li>Na<sup>+</sup>/K<sup>+</sup>-ATPase pump moves Na<sup>+</sup> into the blood.</li><li>Effect of K<sup>+</sup> depletion (hypokalemia, <span>[[Fig. 4-8B|Figure 4-8]]</span>)</li><ul> <li>(1) Hydrogen (H<sup>+</sup>) ions are excreted into the lumen in exchange for Na<sup>+</sup>.</li><li>(2) HCO<sub>3</sub><sup>-</sup> is reabsorbed into the ECF causing metabolic alkalosis.
<blockquote style="color: blue; ">Hypokalemia: increased risk for metabolic alkalosis</blockquote></li> </ul><li>Effect of increased distal delivery of Na<sup>+</sup> from loop/thiazide diuretics acting proximal to this channel
<blockquote style="color: blue; ">Amiloride and triamterene: diuretics with K<sup>+</sup>-sparing effect</blockquote></li><ul> <li>(1) Augmented Na<sup>+</sup> reabsorption and K<sup>+</sup> excretion</li><li>(2) May produce hypokalemia, if K<sup>+</sup> supplements are not taken</li><li>(3) May produce metabolic alkalosis if H<sup>+</sup> exchanges with Na<sup>+</sup> (see earlier)</li> </ul> </ol><li>H<sup>+</sup>/K<sup>+</sup>-ATPase pump (<span>[[Fig. 4-9|Figure 4-9]]</span>)</li><ol type="a"> <li>Located in the collecting tubule; primary site for excretion of H<sup>+</sup> ions</li><li>H<sup>+</sup> ions are secreted into the lumen and K<sup>+</sup> is reabsorbed.</li><li>H<sup>+</sup> combines with HPO<sub>4</sub><sup>2-</sup> to produce NaH<sub>2</sub>PO<sub>4</sub> (titratable acidity).</li><li>H<sup>+</sup> also combines with NH<sub>3</sub> and Cl<sup>-</sup> to produce NH<sub>4</sub>Cl.</li><ul> <li>Most effective way of removing excess H<sup>+</sup> ions</li> </ul><li>Both titratable acid and NH<sub>4</sub>Cl acidify the urine.</li><li>HCO<sub>3</sub><sup>-</sup> is synthesized and reabsorbed into the ECF.</li><ul> <li>Primary site for regenerating (synthesizing) HCO<sub>3</sub><sup>-</sup></li> </ul> </ol><li>Electrolyte changes in Addison's disease (also refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)
<blockquote style="color: blue; ">Spironolactone: aldosterone inhibitor; K<sup>+</sup> sparer</blockquote></li><ol type="a"> <li>Most often due to autoimmune destruction of the adrenal cortex</li><li>Pathogenesis of electrolyte abnormalities</li><ul> <li>Deficiency of aldosterone and other mineralocorticoids</li> </ul><li>Clinical findings</li><ul> <li>(1) Hyponatremia and hyperkalemia</li><ul> <li>(a) Due to inhibition of Na<sup>+</sup> reabsorption and K<sup>+</sup> excretion (see <span>[[Fig. 4-8A|Figure 4-8]]</span>)</li><li>(b) Hypertonic loss of Na<sup>+</sup> in the urine</li><ul> <li>Signs of volume depletion</li> </ul> </ul><li>(2) Retention of H<sup>+</sup> ions, which produces metabolic acidosis</li><ul> <li>Due to dysfunction of the H<sup>+</sup>/K<sup>+</sup>-ATPase pump (see <span>[[Fig. 4-9|Figure 4-9]]</span>)
<blockquote style="color: blue; ">Addison's disease: hyponatremia, hyperkalemia, metabolic acidosis</blockquote></li> </ul> </ul> </ol><li>Primary aldosteronism (Conn's syndrome; also refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li><ol type="a"> <li>Epidemiology</li><ul> <li>Benign adenoma arising in the zona glomerulosa</li> </ul><li>Pathogenesis of electrolyte abnormalities</li><ul> <li>(1) Enhanced activity of aldosterone channels and pumps (see <span>[[Fig. 4-8A|Figure 4-8]]</span>)</li><ul> <li>Increased Na<sup>+</sup> reabsorption and H<sup>+</sup> and K<sup>+</sup> excretion</li> </ul><li>(2) Increased reabsorption of Na<sup>+</sup> causes hypernatremia.</li><li>(3) Increased excretion of K<sup>+</sup> causes hypokalemia.
<blockquote style="color: blue; ">Primary aldosteronism: hypernatremia, hypokalemia, metabolic alkalosis</blockquote></li><ul> <li>Hypokalemia produces severe muscle weakness (see later).</li> </ul><li>(4) Increased excretion of H<sup>+</sup> (see <span>[[Fig. 4-8B|Figure 4-8]]</span>)</li><ul> <li>Causes increased synthesis and reabsorption of HCO<sub>3</sub><sup>-</sup> (metabolic alkalosis)</li> </ul> </ul><li>Effect of excess Na<sup>+</sup> in the ECF</li><ul> <li>(1) Increases plasma volume</li><ul> <li>(a) Increases stroke volume, which increases systolic blood pressure</li><li>(b) Increases peritubular capillary hydrostatic pressure (P<sub>H</sub>)</li><ul> <li>Prevents the proximal tubule from reabsorbing Na<sup>+</sup></li> </ul> </ul><li>(2) Increases renal blood flow</li><ul> <li>Inhibits the renin-angiotensin-aldosterone system causing a decrease in plasma renin activity (PRA)
<blockquote style="color: blue; ">Primary aldosteronism: low plasma renin type of hypertension</blockquote></li> </ul><li>(3) Excess Na<sup>+</sup> enters smooth muscle cells of peripheral resistance arterioles.</li><ul> <li>(a) Na<sup>+</sup> opens up Ca<sup>2+</sup> channels causing vasoconstriction of smooth muscle cells.</li><li>(b) Increased total peripheral resistance increases the diastolic blood pressure.</li> </ul> </ul><li>Summary of clinical findings</li><ul> <li>(1) Hypertension</li><ul> <li>Due to retention of Na<sup>+</sup> (refer to <span macro="tag [[09 Vascular Disorders]] [[Chapter 9]]"></span>)</li> </ul><li>(2) Polyuria and muscle weakness</li><ul> <li>Complication of hypokalemia (see later)</li> </ul><li>(3) Hypernatremia, hypokalemia, metabolic alkalosis</li><li>(4) Decreased PRA</li><li>(5) Absence of pitting edema and effusions
<blockquote style="color: blue; ">Primary aldosteronism: absence of pitting edema</blockquote></li><ul> <li>(a) Due to excessive loss of Na<sup>+</sup> in the urine from inhibition of proximal reabsorption of Na<sup>+</sup> (called the escape mechanism)</li><li>(b) Although TBNa<sup>+</sup> is increased, the amount of Na<sup>+</sup>-containing fluid in the interstitial space is not enough to produce pitting edema.</li> </ul> </ul><li>Treatment is surgery.</li> </ol><li>Bartter's syndrome</li><ol type="a"> <li>Epidemiology</li><ul> <li>Majority of cases occur in children</li> </ul><li>Pathogenesis</li><ul> <li>(1) Renal defect in Cl<sup>-</sup> reabsorption in the Na<sup>+</sup>-K<sup>+</sup>-2 Cl<sup>-</sup> cotransporter</li><ul> <li>Similar to the mechanism of a loop diuretic</li> </ul><li>(2) Loss of Na<sup>+</sup>, K<sup>+</sup>, and Cl<sup>-</sup> ions in the urine</li><ul> <li>Hypertonic loss of Na<sup>+</sup> causes hyponatremia.</li> </ul><li>(3) Augmented exchange of Na<sup>+</sup> and excretion of K<sup>+</sup> in distal/collecting tubules</li><ul> <li>Causes hypokalemia and metabolic alkalosis (see earlier)</li> </ul><li>(4) Hypokalemia stimulates increased prostaglandin synthesis in the kidneys</li><ul> <li>(a) Stimulates hyperplasia of the juxtaglomerular apparatus</li><li>(b) Increased renin causes hyperaldosteronism.</li> </ul> </ul><li>Clinical findings
<blockquote style="color: blue; ">Bartter's syndrome: normotensive</blockquote></li><ul> <li>(1) Patients are normotensive (not hypertensive).</li><ul> <li>Due to vasodilation of peripheral resistance arterioles by prostaglandin
<blockquote style="color: blue; ">Bartter's syndrome: hypokalemia, metabolic alkalosis; ↑ aldosterone and PRA</blockquote></li> </ul><li>(2) Muscle weakness due to hypokalemia</li><li>(3) Increased PRA</li><ul> <li>Decreased PRA in primary aldosteronism.</li> </ul> </ul><li>Treatment</li><ul> <li>(1) K<sup>+</sup>-sparing diuretic</li><ul> <li>Corrects K<sup>+</sup> loss</li> </ul><li>(2) Nonsteroidal anti-inflammatory drug</li><ul> <li>Decreases prostaglandin synthesis</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC004006"></a> <br><a name="PB004013"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Demeclocycline</b> is often used when a patient has a small cell carcinoma of the lung. The drug inhibits the effect of ADH on the collecting tubules (acquired nephrogenic diabetes insipidus), causing loss of fH<sub>2</sub>O in the urine. It is unnecessary to restrict water while the patient is taking the drug.</div><a name="P004004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Normal dilution</li><ol type="a"> <li>UOsm in the late distal tubule/collecting ducts is ∼150 mOsm/kg.</li><ul> <li>(1) Most of the water is fH<sub>2</sub>O.</li><li>(2) Small amount of water is obligated water (oH<sub>2</sub>O) accompanying solute</li> </ul><li>Decreased POsm inhibits ADH release from the posterior pituitary.</li><ul> <li>Absence of ADH results in a loss of fH<sub>2</sub>O in the urine.</li> </ul><li>Positive free water clearance (CH<sub>2</sub>O)</li><ul> <li>(1) CH<sub>2</sub>O = V - COsm</li><ul> <li>V is the volume of urine in mL/min and COsm is obligated water.</li> </ul><li>(2) COsm = UOsm × V/POsm
<blockquote style="color: blue; ">+CH<sub>2</sub>O: indicates dilution; absence of ADH</blockquote></li><li>(3) Positive CH<sub>2</sub>O indicates dilution.</li><ul> <li>Loss of fH<sub>2</sub>O is greater than obligated water.</li> </ul><li>(4) Example-urine volume 10 mL, POsm 250 mOsm/kg, UOsm 150 mOsm/kg</li><ul> <li>COsm = 150 × 10/250 = 6 mL, CH<sub>2</sub>O = 10 - 6 = 4 mL</li> </ul> </ul><li>Syndrome of inappropriate ADH (SIADH; also refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li><ul> <li>(1) Epidemiology</li><ul> <li>(a) Ectopic production of ADH</li><ul> <li>Small cell carcinoma of lung is the most common cause of SIADH.
<blockquote style="color: blue; ">SIADH: small cell carcinoma of lung most common cause</blockquote></li> </ul><li>(b) Drugs that enhance ADH effect</li><ul> <li>Chlorpropamide, cyclophosphamide, phenothiazines, narcotics</li> </ul><li>(c) CNS injury, lung infections (e.g., TB)</li><li>(d) Accounts for nearly 50% of hyponatremia in hospitalized patients</li> </ul><li>(2) Pathophysiology of electrolyte abnormalities</li><ul> <li>(a) Urine is always concentrated, because ADH is always present.</li><ul> <li>Negative CH<sub>2</sub>O; UOsm is greater than POsm
<blockquote style="color: blue; ">SIADH: serum Na<sup>+</sup> < 120 mEq/L; dilution disorder</blockquote></li> </ul><li>(b) Hypotonic gain of water produces a dilutional hyponatremia (see section IB).</li><li>(c) Increased plasma volume increases peritubular capillary hydrostatic pressure (P<sub>H</sub>).
<blockquote style="color: blue; ">Serum Na<sup>+</sup> is usually < 120 mEq/L (136-145 mEq/L).</blockquote></li><ul> <li>Decreased proximal tubular cell reabsorption of Na<sup>+</sup> with random urine Na<sup>+</sup> > 40 mEq/L</li> </ul> </ul><li>(3) Clinical findings</li><ul> <li>(a) Mental status abnormalities from cerebral edema</li><li>(b) Mild SIADH treated by restricting water.</li><li>(c) Acute SIADH treated by combination of slow intravenous drip of hypertonic saline and intravenous furosemide.
<blockquote style="color: blue; ">Treatment of SIADH: restrict water</blockquote></li> </ul> </ul> </ol><li>Normal concentration</li><ol type="a"> <li>Increased POsm stimulates ADH synthesis and release.</li><li>ADH reabsorbs fH<sub>2</sub>O and concentrates the urine.
<blockquote style="color: blue; ">-CH<sub>2</sub> O: concentration; presence of ADH</blockquote></li><li>Negative CH<sub>2</sub>O clearance</li><ul> <li>(1) fH<sub>2</sub>O is reabsorbed back into the blood.
<blockquote style="color: blue; ">0CH<sub>2</sub> O: chronic renal failure; no concentration or dilution</blockquote></li><ul> <li>Loss of obligated water is greater than fH<sub>2</sub>O.</li> </ul><li>(2) Example-urine volume 10 mL, POsm 300 mOsm/kg, UOsm 900 mOsm/kg</li><ul> <li>COsm = 900 × 10/300 = 30 mL, CH<sub>2</sub>O = 10 - 30 = -20 mL</li> </ul> </ul><li>Electrolyte abnormalities in diabetes insipidus (also refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li><ul> <li>(1) Epidemiology</li><ul> <li>(a) Central diabetes insipidus (CDI) is absence of ADH.</li><ul> <li>Causes-CNS trauma and tumors</li> </ul><li>(b) Nephrogenic diabetes insipidus (NDI) is refractoriness to ADH.</li><ul> <li>Causes-drugs (e.g., demeclocycline, lithium) and hypokalemia (see later)</li> </ul> </ul><li>(2) Pathogenesis of electrolyte abnormalities</li><ul> <li>(a) Urine is always diluted and never concentrated.</li><ul> <li>Continual loss of fH<sub>2</sub>O</li> </ul><li>(b) Positive CH<sub>2</sub>O
<blockquote style="color: blue; ">CDI and NDI: hypernatremia, polyuria; concentration disorder</blockquote></li> </ul><li>(3) Clinical and laboratory findings</li><ul> <li>(a) Increased thirst and polyuria</li><li>(b) Hypernatremia due to a loss of water (TBNa<sup>+</sup>/↓↓TBW).
<blockquote style="color: blue; ">CDI: desmopressin ↑UOsm (concentration); NDI: desmopressin no significant ↑ in UOsm</blockquote></li><li>(c) POsm > 295 mOsm/kg and UOsm < 500 mOsm/kg</li> </ul><li>(4) Treatment</li><ul> <li>(a) CDI is treated with desmopressin acetate.</li><li>(b) NDI is treated with thiazides.</li><ul> <li>Volume depletion decreases polyuria.</li> </ul> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC004007"></a> <br><a name="P004005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Functions of potassium</li><ol type="a"> <li>Regulation of neuromuscular excitability and muscle contraction</li><li>Regulation of insulin secretion</li><ul> <li>(1) Hypokalemia inhibits insulin secretion.</li><li>(2) Hyperkalemia stimulates insulin secretion.</li> </ul> </ol><li>Control of potassium</li><ol type="a"> <li>Aldosterone</li><ul> <li>(1) Increases the excretion of K<sup>+</sup> and H<sup>+</sup> in the late distal and collecting tubules (see <span>[[Fig. 4-8A|Figure 4-8]]</span>)</li><li>(2) Increases reabsorption of K<sup>+</sup> by the H<sup>+</sup>/K<sup>+</sup>-ATPase pump in the collecting tubules (see <span>[[Fig. 4-9|Figure 4-9]]</span>)</li> </ul><li>Arterial pH
<blockquote style="color: blue; ">pH changes: may cause shift of K<sup>+</sup> into or out of ICF</blockquote></li><ul> <li>(1) In general, alkalosis causes H<sup>+</sup> to move out of cells and K<sup>+</sup> into cells (<span>[[Fig. 4-10A|Figure 4-10]]</span>).</li><ul> <li>Potential for hypokalemia</li> </ul><li>(2) In general, acidosis causes H<sup>+</sup> to move into cells (for buffering) and K<sup>+</sup> out of cells (<span>[[Fig. 4-10B|Figure 4-10]]</span>).</li><ul> <li>Potential for hyperkalemia
<blockquote style="color: blue; ">Insulin, β<sub>2</sub>-agonist (e.g., albuterol): may shift K<sup>+</sup> into cell; hypokalemia Digitalis, β-blocker, succinylcholine: may shift K<sup>+</sup> out of the cell; hyperkalemia Loop and thiazide diuretics: most common cause of hypokalemia</blockquote></li> </ul><li>(3) Exception-in diarrhea, there is a loss of K<sup>+</sup> and HCO<sub>3</sub><sup>-</sup> in the stool, the former producing hypokalemia and the latter metabolic acidosis.</li> </ul> </ol><li>Hypokalemia (serum K<sup>+</sup> < 3.5 mEq/L)</li><ol type="a"> <li>Causes of hypokalemia (<span>[[Table 4-3|Table 4-3. CAUSES OF HYPOKALEMIA]]</span>)</li><li>Clinical findings</li><ul> <li>(1) Muscle weakness</li><ul> <li>Due to changes in the intracellular/extracellular K<sup>+</sup> membrane potential</li> </ul><li>(2) U waves on an electrocardiogram (ECG; <span>[[Fig. 4-11|Figure 4-11]]</span>)</li><li>(3) Polyuria
<blockquote style="color: blue; ">Hypokalemia: ECG shows U wave</blockquote></li><ul> <li>(a) Collecting tubules are refractory to ADH (i.e., nephrogenic diabetes insipidus).</li><li>(b) Tubule cells become distended with fluid (called vacuolar nephropathy).</li> </ul><li>(4) Rhabdomyolysis</li><ul> <li>Hypokalemia inhibits insulin, which decreases muscle glycogenesis, leading to rhabdomyolysis.
<blockquote style="color: blue; ">Renal failure: most common cause of hyperkalemia</blockquote></li> </ul> </ul> </ol><li>Hyperkalemia (serum K<sup>+</sup> > 5 mEq/L)</li><ol type="a"> <li>Causes (<span>[[Table 4-4|Table 4-4. CAUSES OF HYPERKALEMIA]]</span>)</li><li>Clinical findings</li><ul> <li>(1) Ventricular arrhythmias
<blockquote style="color: blue; ">Pseudohyperkalemia: RBC hemolysis from difficult venipuncture</blockquote></li><ul> <li>Severe hyperkalemia (e.g., 7-8 mEq/L) causes the heart to stop in diastole.</li> </ul><li>(2) Peaked T waves on an ECG (<span>[[Fig. 4-12|Figure 4-12]]</span>)
<blockquote style="color: blue; ">Hyperkalemia: ECG shows peaked T waves</blockquote></li><ul> <li>Due to accelerated repolarization of cardiac muscle</li> </ul><li>(3) Muscle weakness</li><ul> <li>Hyperkalemia partially depolarizes the cell membrane which interferes with membrane excitability.</li> </ul> </ul> </ol> </ol>
</div><a name="B004001"></a><div class="BT">BOX 4-1 VOLUME CONTROL</div><a name="PB004014"></a><div class="BB" style="color: rgb(47, 79, 79); ">Protection of the intravascular volume is paramount to normal survival. Maintenance of the extracellular fluid (ECF) volume involves the integration of factors that (1) control thirst (e.g., increased POsm and angiotensin II [ATII]), (2) activate the renin-angiotensin-aldosterone (RAA) system (e.g., reduced renal blood flow, sympathetic nervous system stimulation), (3) stimulate the baroreceptors in the arterial circulation (e.g., decreased effective arterial blood volume), (4) increase free water reabsorption to concentrate the urine (e.g., antidiuretic hormone), and (5) increase renal reabsorption of Na<sup>+</sup> and water.</div><a name="PB004015"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Effective Arterial Blood Volume</b></div><a name="PB004016"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Effective arterial blood volume (EABV)</b> is a conceptual term that refers to that portion of the ECF that is in the vascular space. In most instances, it correlates directly with the ECF volume and TBNa<sup>+</sup> status of the individual (i.e., ↓ EABV // ↓ ECF/↓ TBNa<sup>+</sup> or ↑ EABV // ↑ ECF/↑ TBNa<sup>+</sup>). However, in edema states, where there is an alteration in Starling pressures (e.g., right-sided heart failure), the redistribution of fluid (a transudate) from the intravascular compartment into the interstitial fluid compartment increases the total ECF volume at the expense of reducing the venous return of blood to the right side of the heart, reducing cardiac output, and reducing EABV (↓ EABV // ↑ ECF/↑ TBNa<sup>+</sup>). Hence, an increase in total ECF volume does not always correlate with an increase in the EABV.</div><a name="PB004017"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Baroreceptors and the Renin-Angiotensin-Aldosterone System</b></div><a name="PB004018"></a><div class="BB" style="color: rgb(47, 79, 79); ">Control of the EABV is monitored by the pressure impacting upon the high pressure arterial baroreceptors located in the aortic arch and carotid sinus, and the flow of blood to the renal arteries. When the baroreceptors are activated by a decreased EABV, signals are sent to the medulla to increase sympathetic tone leading to release of catecholamines resulting in vasoconstriction of peripheral resistance arterioles (increases diastolic blood pressure), venoconstriction (increases venous return to the heart), increases heart rate (chronotropic effect), and increases cardiac contractility (inotropic effect). Signals are also sent to the supraoptic and paraventricular nuclei in the hypothalamus to synthesize and release antidiuretic hormone (ADH, vasopressin), the latter from nerve endings located in the posterior pituitary. ADH enhances the reabsorption of free water (fH<sub>2</sub>O; water without electrolytes) from the collecting tubules in the kidneys and is a potent vasoconstrictor of the peripheral resistance vessels. Finally, the RAA system is activated owing to reduced blood flow to the juxtaglomerular (JG) apparatus located in the afferent arterioles and by direct sympathetic stimulation of the JG apparatus with subsequent release of the enzyme renin. Renin initiates the following reaction sequence: it cleaves renin substrate (angiotensinogen) into <b>angiotensin I</b> (ATI), which is converted by pulmonary <b>angiotensin converting enzyme</b> (ACE) into <b>angiotensin II</b> (ATII). ATII has a threefold function:
<ol type="1"> <li>Vasoconstriction of peripheral resistance arterioles</li><li>Stimulation of aldosterone synthesis and release from the zona glomerulosa (increases Na<sup>+</sup> reabsorption in exchange for potassium ions [K<sup>+</sup>] and hydrogen ions [H<sup>+</sup>])</li><li>Direct stimulation of the thirst center in the brain</li> </ol></div><a name="PB004019"></a><div class="BB" style="color: rgb(47, 79, 79); ">All of these events are an attempt to increase the EABV before medical intervention.</div><a name="PB004020"></a><div class="BB" style="color: rgb(47, 79, 79); ">In contradistinction, when there is an increase in EABV, there are many counterregulatory mechanisms that come into play to eliminate the excess fluid prior to medical intervention. An increase in EABV is associated with a corresponding increase in cardiac output. This stretches the arterial baroreceptors, which triggers cessation of sympathetic outflow from the medulla. This, in turn, leads to inhibition of ADH synthesis and release, vasodilation of peripheral resistance arterioles, decreased cardiac contraction, inhibition of the RAA system, and decreased renal retention of Na<sup>+</sup> and water. Other counterregulatory factors also come into play including <b>atrial natriuretic peptide</b> (ANP), <b>prostaglandin E<sub>2</sub></b>, and <b>brain natriuretic peptide (BNP)</b>. ANP is released from the left and right atria in response to atrial distention (e.g., left- and/or right-sided heart failure). ANP has multiple functions including (1) suppression of ADH release, (2) inhibition of the effect of ATII on stimulating thirst and aldosterone secretion, (3) vasodilation of the peripheral resistance vessels, (4) direct inhibition of Na<sup>+</sup> reabsorption in the kidneys (diuretic effect), and (5) suppression of renin release. Prostaglandin E<sub>2</sub> (1) inhibits ADH, (2) blocks Na<sup>+</sup> reabsorption in the kidneys, and (3) is a potent intrarenal vasodilator that offsets the vasoconstrictive effects of ATII and the catecholamines. BNP increases in the blood when the right and/or left ventricles are volume overloaded (e.g., left- and/or right-sided heart failure).</div><a name="PB004021"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Renal Mechanisms in Volume Regulation</b></div><a name="PB004022"></a><div class="BB" style="color: rgb(47, 79, 79); ">The response of the kidney to volume alterations is closely integrated with many of the events previously described. The reabsorption of solutes from the proximal tubules is dependent on the <b>filtration fraction</b> (FF) in the glomerulus in concert with Starling pressures that are operative in the peritubular capillaries. The FF is the fraction of the <b>renal plasma flow</b> (RPF) that is filtered across the glomerular capillaries into the tubular lumen. It is calculated by dividing the <b>glomerular filtration rate</b> (GFR) by the RPF (FF = GFR ÷ RPF). Normally, the FF is ∼20%, with the remaining 80% of the RPF entering the efferent arterioles, which divide to form the intricate peritubular capillary microcirculation. Because prostaglandin E<sub>2</sub>, a vasodilator, controls the afferent arteriolar blood flow into the glomerulus and ATII, a vasoconstrictor, monitors the efferent arteriolar blood flow leaving the glomerulus, the FF is significantly affected by alterations in their concentrations. Starling pressures in the peritubular capillaries determine how much of the fluid from the proximal tubule is reabsorbed back into the ECF compartment. A low peritubular capillary hydrostatic pressure (P<sub>H</sub>) coupled with a high oncotic pressure (P<sub>O</sub>) is responsible for enhancing the reabsorption of solutes from the tubular lumen into the tubular cell out into the lateral intercellular space, and into the peritubular capillary (A). This occurs when the EABV is decreased (e.g., ECF volume depletion, or hypovolemia). A high P<sub>H</sub> coupled with a low P<sub>O</sub> results in the loss of solutes in the urine in conditions when the EABV is increased (B; e.g., ECF volume overload, or hypervolemia). When hypovolemia is present in the ECF, the EABV is reduced and the FF is increased (↑FF = ↓GFR ÷ ↓↓RPF), hence increasing the filtered load of Na<sup>+</sup> and other solutes. The P<sub>H</sub> is decreased and the P<sub>O</sub> is increased, resulting in the reabsorption of the filtered Na<sup>+</sup> plus other solutes into the ECF compartment (e.g., urea) in isosmotic proportions. The above mechanism is so effective that a <b>random urine Na</b><sup>+</sup> (UNa<sup>+</sup>) measurement is usually < 20 mEq/L and is often 0 when hypovolemia is extreme. In the presence of an increased EABV, or hypervolemia, the FF is decreased (↓FF = ↑GFR ÷ ↑↑RPF), the filtered load of Na<sup>+</sup> and other solutes is decreased, the P<sub>H</sub> is increased and the P<sub>O</sub> is decreased, hence favoring loss of the filtered Na<sup>+</sup> plus other solutes (e.g., urea, uric acid) in the urine (random UNa<sup>+</sup> > 20 mEq/L).<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g011.jpg" id="">
</div></html>
![[4.I.A.Body fluid compartments]]
<<tiddler [[4.I.A.Body fluid compartments]]>>
![[4.I.B.Isotonic, hypotonic, and hypertonic disorders]]
<<tiddler [[4.I.B.Isotonic, hypotonic, and hypertonic disorders]]>>
![[4.I.C.Volume control (Box 4-1)]]
<<tiddler [[4.I.C.Volume control (Box 4-1)]]>>
![[4.I.D.Correlation of nephron cotransporters and pumps with electrolyte disorders]]
<<tiddler [[4.I.D.Correlation of nephron cotransporters and pumps with electrolyte disorders]]>>
![[4.I.E.Dilution and concentration of urine]]
<<tiddler [[4.I.E.Dilution and concentration of urine]]>>
![[4.I.F.Potassium (K+) disorders]]
<<tiddler [[4.I.F.Potassium (K+) disorders]]>>
<html><a name="HC004009"></a> <br><a name="PB004023"></a><div class="BB" style="color: rgb(47, 79, 79); ">Compensation refers to respiratory and renal mechanisms that bring the arterial pH close to but not into the normal pH range (7.35-7.45). In primary respiratory acidosis and alkalosis, compensation is metabolic alkalosis and metabolic acidosis, respectively. In primary metabolic acidosis and alkalosis, compensation is respiratory alkalosis and respiratory acidosis, respectively. When the expected compensation remains in the normal range, an uncompensated disorder is present. If compensation moves outside the normal range but does not bring pH into the normal range, a partially compensated disorder is present. When compensation brings the pH into the normal range, full compensation is present, which rarely occurs.</div><a name="P004018"></a><div class="PA" style="color: black; "><ol type="1"> <li>Respiratory acidosis</li><ol type="a"> <li>Causes of respiratory acidosis (<span>[[Table 4-5|Table 4-5. CAUSES OF RESPIRATORY ACIDOSIS AND ALKALOSIS]]</span>)
<blockquote style="color: blue; ">Chronic bronchitis due to smoking: common cause of respiratory acidosis</blockquote></li><li>Pathogenesis</li><ul> <li>(1) Alveolar hypoventilation with retention of CO<sub>2</sub></li><li>(2) Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg
<blockquote style="color: blue; ">Respiratory acidosis: Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg</blockquote></li><ul> <li>↓ pH ∼ ↑ HCO<sub>3</sub><sup>-</sup>/↑↑P<span style="font-variant:small-caps;">co</span><sub>2</sub></li> </ul> </ul><li>Metabolic alkalosis is compensation</li><ul> <li>(1) Serum HCO<sub>3</sub><sup>-</sup> ≤ 30 mEq/L in acute respiratory acidosis</li><li>(2) Serum HCO<sub>3</sub><sup>-</sup> > 30 mEq/L (indicates renal compensation) in chronic respiratory acidosis
<blockquote style="color: blue; ">Full compensation: rarely occurs</blockquote></li> </ul><li>Calculation of expected compensation in acute respiratory acidosis
<blockquote style="color: blue; ">Formulas: help recognize single versus multiple acid-base disorders</blockquote></li><ul> <li>(1) Sometimes calculations help in identifying whether there is more than one primary acid-base disorder in a patient (called a mixed disorder; see later).</li><li>(2) If the calculated expected compensation closely approximates the measured compensation, a single primary disorder is present.</li><li>(3) If there is an obvious disparity between calculated expected compensation and measured compensation, another primary disorder is also present.</li><li>(4) In acute respiratory acidosis, expected HCO<sub>3</sub><sup>-</sup> compensation = 0.1 × ΔP<span style="font-variant:small-caps;">co</span><sub>2</sub> (difference from normal of 40 mm Hg)</li><li>(5) Example-pH 7.2, P<span style="font-variant:small-caps;">co</span><sub>2</sub> 74 mm Hg, HCO<sub>3</sub><sup>-</sup> 27 mEq/L</li><ul> <li>(a) Expected HCO<sub>3</sub><sup>-</sup> compensation = 0.1 × (74 - 40) = 3.4 mEq/L increase above normal</li><li>(b) Expected HCO<sub>3</sub><sup>-</sup> compensation = 24 mEq/L (mean HCO<sub>3</sub><sup>-</sup>) + 3.4 = 27. 4 mEq/L</li><ul> <li>Note that measured and expected calculated HCO<sub>3</sub><sup>-</sup> values are similar; therefore, a single disorder is present.</li> </ul> </ul> </ul><li>Calculation of expected compensation in chronic respiratory acidosis</li><ul> <li>(1) Expected HCO<sub>3</sub><sup>-</sup> compensation = 0.4 × ΔP<span style="font-variant:small-caps;">co</span><sub>2</sub></li><li>(2) Example-pH 7.34, P<span style="font-variant:small-caps;">co</span><sub>2</sub> 60 mm Hg, HCO<sub>3</sub><sup>-</sup> 32 mEq/L</li><ul> <li>(a) Expected HCO<sub>3</sub><sup>-</sup> compensation = 0.4 × (60 - 40) = 8 mEq/L increase above normal</li><li>(b) Expected HCO<sub>3</sub><sup>-</sup> compensation = 24 + 8 = 32 mEq/L</li><ul> <li>Note that measured and expected calculated HCO<sub>3</sub><sup>-</sup> values are similar; therefore, a single disorder is present.</li> </ul> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Somnolence</li><li>(2) Cerebral edema (vasodilation of cerebral vessels)</li> </ul> </ol><li>Respiratory alkalosis</li><ol type="a"> <li>Causes of respiratory alkalosis (see <span>[[Table 4-5|Table 4-5. CAUSES OF RESPIRATORY ACIDOSIS AND ALKALOSIS]]</span>)
<blockquote style="color: blue; ">Anxiety: most common cause of respiratory alkalosis</blockquote></li><li>Pathogenesis</li><ul> <li>(1) Alveolar hyperventilation with elimination of CO<sub>2</sub></li><li>(2) Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> < 33 mm Hg
<blockquote style="color: blue; ">Respiratory alkalosis: Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> < 33 mm Hg</blockquote></li><ul> <li>↑ pH ∼ ↓ HCO<sub>3</sub><sup>-</sup>/↓↓ P<span style="font-variant:small-caps;">co</span><sub>2</sub></li> </ul> </ul><li>Metabolic acidosis is compensation.</li><ul> <li>(1) Serum HCO<sub>3</sub><sup>-</sup> ≥ 18 mEq/L in acute respiratory alkalosis</li><li>(2) Serum HCO<sub>3</sub><sup>-</sup> < 18 mEq/L but > 12 mEq/L (indicates renal compensation) in chronic respiratory alkalosis</li> </ul><li>Calculation of expected compensation in acute respiratory alkalosis</li><ul> <li>(1) Expected HCO<sub>3</sub><sup>-</sup> compensation = 0.2 × ΔPa<span style="font-variant:small-caps;">co</span><sub>2</sub> (difference from normal of 40 mm Hg)</li><li>(2) Example: pH 7.56, Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> 24 mm Hg, HCO<sub>3</sub><sup>-</sup> 21 mEq/L</li><ul> <li>(a) Expected HCO<sub>3</sub><sup>-</sup> compensation = 0.2 × (40 - 24) = 3.2 mEq/L less than the normal</li><li>(b) Expected HCO<sub>3</sub><sup>-</sup> compensation = 24 mEq/L (mean HCO<sub>3</sub><sup>-</sup>) - 3.2 = 20.8 mEq/L</li><ul> <li>Note that measured and expected calculated HCO<sub>3</sub><sup>-</sup> values are similar; therefore, a single disorder is present.</li> </ul> </ul> </ul><li>Calculation of expected compensation in chronic respiratory alkalosis</li><ul> <li>(1) Expected HCO<sub>3</sub><sup>-</sup> = 0.5 × ΔPa<span style="font-variant:small-caps;">co</span><sub>2</sub></li><li>(2) Example: pH 7.47, Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> 18 mm Hg, HCO<sub>3</sub><sup>-</sup> 13 mEq/L</li><ul> <li>(a) Expected HCO<sub>3</sub><sup>-</sup> compensation = 0.5 × (40 - 18) = 11 mEq/L less than the normal</li><li>(b) Expected HCO<sub>3</sub><sup>-</sup> compensation = 24 - 11 = 13 mEq/L</li><ul> <li>Note that measured and expected calculated HCO<sub>3</sub><sup>-</sup> values are similar; therefore, a single disorder is present.</li> </ul> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Light-headedness and confusion</li><li>(2) Signs of tetany
<blockquote style="color: blue; ">Tetany: commonly occurs in acute respiratory alkalosis</blockquote></li><ul> <li>(a) Thumb adduction into the palm (carpopedal spasm)</li><li>(b) Perioral twitching when the facial nerve is tapped (Chvostek sign)</li><li>(c) Perioral numbness and tingling</li> </ul> </ul> </ol> </ol>
</div><a name="PB004024"></a><div class="BB" style="color: rgb(47, 79, 79); ">Alkalosis increases the number of negative charges on albumin (more COO<sup>-</sup> groups on acidic amino acids). Therefore, calcium is displaced from the ionized calcium fraction and is bound to albumin, causing a decrease in ionized calcium levels and signs of tetany (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>).</div></html>
![[4.II.A.Primary alterations in arterial Pco2 (Paco2 = 33-45 mm Hg)]]
<<tiddler [[4.II.A.Primary alterations in arterial Pco2 (Paco2 = 33-45 mm Hg)]]>>
![[4.II.B.Primary alterations in HCO3- (22-28 mEq/L)]]
<<tiddler [[4.II.B.Primary alterations in HCO3- (22-28 mEq/L)]]>>
![[4.II.C.Mixed acid-base disorders]]
<<tiddler [[4.II.C.Mixed acid-base disorders]]>>
![[4.II.D.Selected electrolyte profiles (Table 4-9)]]
<<tiddler [[4.II.D.Selected electrolyte profiles (Table 4-9)]]>>
![[4.II.E.Selected arterial blood gas profiles (Table 4-10)]]
<<tiddler [[4.II.E.Selected arterial blood gas profiles (Table 4-10)]]>>
<html><a name="HC004010"></a> <br><a name="PB004025"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Calculation of the osmolal gap</b> is useful in evaluating causes of an increased AG metabolic acidosis. The plasma osmolality (POsm) is calculated as follows: POsm = 2 (serum Na<sup>+</sup>) + serum glucose/18 + serum blood urea nitrogen/2.8 + serum ethanol (mg/dL)/4.6 (if the patient is drinking ethanol) and is then subtracted from the measured POsm. A difference of <10 mOsm/kg is normal. A difference of >10 mOsm/kg is highly suspicious for methanol or ethylene glycol poisoning.</div><a name="P004019"></a><div class="PA" style="color: black; "><ul> <li>Applies to venous and arterial bicarbonate</li><ol type="1"> <li>Metabolic acidosis</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Serum HCO<sub>3</sub><sup>-</sup> < 22 mEq/L
<blockquote style="color: blue; ">Metabolic acidosis: HCO<sub>3</sub><sup>-</sup> < 22 mEq/L</blockquote></li><ul> <li>↓ pH ∼ ↓↓ HCO<sub>3</sub><sup>-</sup>/↓ P<span style="font-variant:small-caps;">co</span><sub>2</sub></li> </ul><li>(2) Addition of an acid (increased AG type)</li><li>(3) Loss of HCO<sub>3</sub><sup>-</sup> or inability to synthesize HCO<sub>3</sub><sup>-</sup> (normal AG type)</li> </ul><li>Respiratory alkalosis is compensation.</li><li>Calculation of the expected compensation in metabolic acidosis (either type)</li><ul> <li>(1) Expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> = 1.2 × ΔHCO<sub>3</sub><sup>-</sup> +/- 2</li><ul> <li>ΔHCO<sub>3</sub><sup>-</sup> is measured HCO<sub>3</sub><sup>-</sup> subtracted from the mean HCO<sub>3</sub><sup>-</sup> of 24 mEq/L.</li> </ul><li>(2) Example: pH 7.27, Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> 27 mm Hg, HCO<sub>3</sub><sup>-</sup> 12 mEq/L</li><ul> <li>(a) Expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> compensation = 1.2 × (24 - 12) = 14.4 mm Hg less than the normal</li><li>(b) Expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> = 40 (mean Pa<span style="font-variant:small-caps;">co</span><sub>2</sub>) - 14.4 = 25.6 mm Hg (23.6-27.6)</li><ul> <li>Note that measured Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> is within the calculated range; therefore, only a single disorder is present.</li> </ul> </ul> </ul><li>Increased anion gap (AG) type</li><ul> <li>(1) Formula for calculating anion gap:</li><ul> <li>(a) AG = serum Na<sup>+</sup> - (serum Cl<sup>-</sup> + serum HCO<sub>3</sub><sup>-</sup>) = 12 mEq ± 2, where the 12 mEq/L represent the anions that are <i>not</i> accounted for in the formula (e.g., phosphate, albumin, sulfate).</li><li>(b) Therefore, if the AG is greater than 12 mEq/L ± 2, there must be additional anions present that should not be there (e.g., lactate, salicylate, acetoacetate, β-hydroxybutyrate anions).</li> </ul><li>(2) In increased AG metabolic acidosis, excess H<sup>+</sup> ions of an acid (e.g., lactic acid) are buffered by HCO<sub>3</sub><sup>-</sup>, which decreases the serum HCO<sub>3</sub><sup>-</sup>.</li><li>(3) HCO<sub>3</sub><sup>-</sup> loss due to buffering is counterbalanced by the anions of the acid (e.g., lactate anions), which maintains electroneutrality.
<blockquote style="color: blue; ">↑ AG metabolic acidosis: anions of acid replace buffered HCO<sub>3</sub><sup>-</sup></blockquote></li><ul> <li>Example-for every HCO<sub>3</sub><sup>-</sup> ion that is lost, there is a lactate anion to replace it.
<blockquote style="color: blue; ">Lactic acidosis: most common ↑ AG metabolic acidosis; e.g., anaerobic glycolysis in shock</blockquote></li> </ul><li>(4) Example-serum Na<sup>+</sup> 130 mEq/L (135-147), serum Cl<sup>-</sup> 88 mEq/L (95-105), serum HCO<sub>3</sub><sup>-</sup> 10 mEq/L (22-28)</li><ul> <li>AG = 130 - (88 + 10) = 32 mEq/L (12 mEq/L ± 2).</li> </ul><li>(5) Causes of increased AG metabolic acidosis (<span>[[Table 4-6|Table 4-6. CAUSES OF INCREASED ANION GAP METABOLIC ACIDOSIS]]</span>)</li> </ul><li>Normal AG metabolic acidosis</li><ul> <li>(1) Due to a loss of HCO<sub>3</sub><sup>-</sup> or an inability to synthesize (regenerate) or reclaim HCO<sub>3</sub><sup>-</sup> in the kidneys</li><li>(2) Cl<sup>-</sup> anions increase to counterbalance the loss of HCO<sub>3</sub><sup>-</sup> anions in order to maintain electroneutrality.</li><ul> <li>Produces a hyperchloremic normal AG metabolic acidosis
<blockquote style="color: blue; ">Normal AG metabolic acidosis: Cl<sup>-</sup> anions replace HCO<sub>3</sub><sup>-</sup></blockquote></li> </ul><li>(3) Example-serum Na<sup>+</sup> 136 mEq/L, serum Cl<sup>-</sup> 110 mEq/L, serum HCO<sub>3</sub><sup>-</sup> 14 mEq/L</li><ul> <li>(a) AG = 136 - (110 + 14) = 12 mEq/L.</li><li>(b) Drop of 10 mEq/L of HCO<sub>3</sub><sup>-</sup> from normal (24 - 14 = 10) is counterbalanced by a gain of 10 mEq/L of Cl<sup>-</sup> ions (100 + 10 = 110), hence the term hyperchloremic normal AG metabolic acidosis.</li> </ul><li>(4) Causes of normal AG metabolic acidosis (<span>[[Table 4-7|Table 4-7. CAUSES OF NORMAL ANION GAP METABOLIC ACIDOSIS]]</span>)</li> </ul><li>Clinical findings</li><ul> <li>(1) Hyperventilation (Kussmaul breathing)</li><li>(2) Warm shock</li><ul> <li>Acidosis vasodilates peripheral resistance arterioles.</li> </ul><li>(3) Osteoporosis</li><ul> <li>Bone buffers excess H<sup>+</sup> ions.</li> </ul> </ul> </ol><li>Metabolic alkalosis</li><ol type="a"> <li>Causes of metabolic alkalosis (<span>[[Table 4-8|Table 4-8. CAUSES OF METABOLIC ALKALOSIS]]</span>)
<blockquote style="color: blue; ">Loop and thiazide diuretics: most common cause of metabolic alkalosis</blockquote></li><li>Pathogenesis</li><ul> <li>(1) Due to a loss of H<sup>+</sup> ions or a gain in HCO<sub>3</sub><sup>-</sup></li><li>(2) Serum HCO<sub>3</sub><sup>-</sup> > 28 mEq/L</li><ul> <li>pH ∼ ↑↑ HCO<sub>3</sub><sup>-</sup>/↑P<span style="font-variant:small-caps;">co</span><sub>2</sub>
<blockquote style="color: blue; ">Metabolic alkalosis: HCO<sub>3</sub><sup>-</sup> > 28 mEq/L</blockquote></li> </ul> </ul><li>Respiratory acidosis is compensation.</li><li>Calculation of expected compensation in metabolic alkalosis</li><ul> <li>(1) Expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> = 0.7 × ΔHCO<sub>3</sub><sup>-</sup> ± 2</li><li>(2) Example: pH 7.58, Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> 49 mm Hg, HCO<sub>3</sub><sup>-</sup> 39 mEq/L</li><ul> <li>(a) Expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> compensation = 0.7 × (39 - 24) = 10.5 greater than the normal</li><li>(b) Expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> compensation = 40 + 10.5 = 50.5 mm Hg (48.5-52.5)</li><ul> <li>Note that measured Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> is within the calculated range; therefore, only a single disorder is present.</li> </ul> </ul> </ul><li>Clinical findings</li><ul> <li>(1) Increased risk for ventricular arrhythmias</li><li>(2) Metabolic alkalosis left-shifts the oxygen-binding curve and its compensation, respiratory acidosis, decreases arterial P<span style="font-variant:small-caps;">o</span><sub>2</sub> causing hypoxia in cardiac muscle, which precipitates ventricular arrhythmias.</li> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC004011"></a> <br><a name="P004020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Blend of two or more primary acid-base disorders occurring at the same time</li><li>Clues that suggest a mixed disorder
<blockquote style="color: blue; ">Clues for mixed disorder: normal pH; extreme change in pH</blockquote></li><ol type="a"> <li>Presence of a normal pH due to a combination of a primary acidosis and a primary alkalosis</li><ul> <li>(1) Salicylate intoxication, particularly in adults
<blockquote style="color: blue; ">Salicylate intoxication: often mixture of primary metabolic acidosis and primary respiratory alkalosis; normal pH</blockquote></li><ul> <li>(a) Salicylic acid produces a primary metabolic acidosis.</li><li>(b) Salicylates overstimulate the respiratory center causing primary respiratory alkalosis.</li> </ul><li>(2) Patient with chronic bronchitis who is taking a loop diuretic</li><ul> <li>(a) Chronic bronchitis produces a primary respiratory acidosis.</li><li>(b) Loop diuretics produce a primary metabolic alkalosis.</li> </ul> </ul><li>Extreme acidemia due to a primary metabolic acidosis plus a primary respiratory acidosis</li><ul> <li>Example-cardiorespiratory arrest with primary respiratory acidosis (no ventilation) and primary metabolic acidosis (lactic acidosis from hypoxia)</li> </ul> </ol><li>Examples of how formulas help to identify a mixed disorder</li><ol type="a"> <li>pH 7.26, Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> 38 mm Hg, HCO<sub>3</sub><sup>-</sup> 17 mEq/L</li><ul> <li>(1) Presumptive diagnosis: metabolic acidosis (HCO<sub>3</sub><sup>-</sup> < 22 mEq/L) without compensation (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> in normal range)</li><li>(2) Formula for calculating expected compensation in metabolic acidosis</li><ul> <li>(a) Expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> = 1.2 × ΔHCO<sub>3</sub><sup>-</sup> ± 2</li><li>(b) Expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> = 1.2 × (24 - 17) = 8.4 mm Hg less than the normal value</li><li>(c) Expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> = 40 (mean Pa<span style="font-variant:small-caps;">co</span><sub>2</sub>) - 8.4 = 31.6 (29.6-33.6)</li><li>(d) The measured Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> is 38 mm Hg, which is higher than it should be, indicating that a respiratory acidosis (retention of CO<sub>2</sub>) must also be present as a primary disorder.</li> </ul> </ul><li>pH 7.38, Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> 70 mm Hg, HCO<sub>3</sub><sup>-</sup> 41 mEq/L</li><ul> <li>(1) Presumptive diagnosis: mixed disorder (because the pH is normal) with chronic respiratory acidosis (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg, HCO<sub>3</sub><sup>-</sup> > 30 mEq/L) and primary metabolic alkalosis (HCO<sub>3</sub><sup>-</sup> > 28 mEq/L)</li><li>(2) Using either the formula for metabolic alkalosis or chronic respiratory acidosis will prove the presence of a mixed disorder.</li><li>(3) Using the chronic respiratory acidosis formula (expected HCO<sub>3</sub><sup>-</sup> = 0.4 × ΔPa<span style="font-variant:small-caps;">co</span><sub>2</sub>)</li><ul> <li>(a) Expected HCO<sub>3</sub><sup>-</sup> compensation = 0.4 × (70 - 40) = 12 mEq/L increase above normal</li><li>(b) Expected HCO<sub>3</sub><sup>-</sup> compensation = 24 + 12 = 36 mEq/L</li><li>(c) Measured HCO<sub>3</sub><sup>-</sup> is 41 mEq/L, which is higher than the expected compensation indicating the presence of an additional primary metabolic alkalosis (more HCO<sub>3</sub><sup>-</sup> than there should be for compensation).</li> </ul><li>(4) Using the metabolic alkalosis formula (expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> = 0.7 × ΔHCO<sub>3</sub><sup>-</sup> ± 2)</li><ul> <li>(a) Expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> = 0.7 × (41 - 24) = 11.9 mm Hg increase from the normal</li><li>(b) Expected Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> = 40 + 11.9 = 51.9 mm Hg (49.9-53.9)</li><li>(c) The measured Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> is 70 mm Hg, which is much higher than it should be indicating the presence of an additional primary respiratory acidosis.</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC004012"></a><span>[[Table 4-9|Table 4-9. SELECTED ELECTROLYTE PROFILES]]</span> <br> <br><a name="P004021"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">pH defines what is the primary disorder versus what is the compensation.</blockquote>
</div></html>
<html><a name="HC004013"></a><span>[[Table 4-10|Table 4-10. SELECTED ARTERIAL BLOOD GAS PROFILES]]</span> <br> <br></html>
<html><a name="HC004015"></a> <br><a name="P004023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Transudate
<blockquote style="color: blue; ">Transudate: protein-poor and cell-poor fluid</blockquote></li><ol type="a"> <li>Protein-poor (<3 g/dL) and cell-poor fluid</li><li>Produces dependent pitting edema and body cavity effusions
<blockquote style="color: blue; ">Pitting edema: transudate; ↑ hydrostatic pressure and/or ↓ oncotic pressure</blockquote></li><li>Associated with an alteration in Starling pressures (see section IB1)</li> </ol><li>Exudate
<blockquote style="color: blue; ">Exudate: protein-rich and cell-rich fluid</blockquote></li><ol type="a"> <li>Protein-rich (>3 g/dL) and cell-rich (e.g., neutrophils) fluid</li><li>Produces swelling of tissue but no pitting edema</li> </ol><li>Lymphedema</li><ol type="a"> <li>Protein-rich fluid</li><li>Nonpitting edema</li> </ol><li>Glycosaminoglycans</li><ol type="a"> <li>Increase in hyaluronic acid and chondroitin sulfate</li><li>Nonpitting edema called myxedema</li> </ol> </ol>
</div></html>
<html><a name="HC004016"></a> <br><a name="P004024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Alteration in Starling pressure</li><ol type="a"> <li>Produces a transudate</li><li>Clinical examples of increased vascular hydrostatic pressure</li><ul> <li>(1) Pulmonary edema in left-sided heart failure</li><li>(2) Peripheral pitting edema in right-sided heart failure (see <span>[[Fig. 4-4|Figure 4-4]]</span>)</li><li>(3) Portal hypertension in cirrhosis producing ascites (see <span>[[Fig. 18-9|Figure 18-9]]</span>)</li> </ul><li>Clinical examples of decreased vascular plasma oncotic pressure (hypoalbuminemia)</li><ul> <li>(1) Malnutrition with decreased protein intake (see <span>[[Fig. 7-1|Figure 7-1]]</span>, left)</li><li>(2) Cirrhosis with decreased synthesis of albumin</li><li>(3) Nephrotic syndrome with increased loss of protein in urine (>3.5 g/24 hours)</li><li>(4) Malabsorption with decreased reabsorption of protein
<blockquote style="color: blue; ">Pitting edema: right-sided heart failure due to ↑ hydrostatic pressure; cirrhosis due to ↓ oncotic pressure</blockquote></li> </ul><li>Renal retention of sodium and water</li><ul> <li>(1) Increases hydrostatic pressure (increased plasma volume)</li><li>(2) Decreases oncotic pressure (dilutional effect on albumin)</li><li>(3) Examples-acute renal failure, glomerulonephritis</li> </ul> </ol><li>Increased vascular permeability</li><ol type="a"> <li>Produces an exudate</li><li>Example-acute inflammation (e.g., tissue swelling following a bee sting)</li> </ol><li>Lymphatic obstruction</li><ol type="a"> <li>Produces lymphedema</li><li>Examples</li><ul> <li>(1) Lymphedema following modified radical mastectomy and radiation (see <span>[[Fig. 9-8|Figure 9-8]]</span>)
<blockquote style="color: blue; ">Lymphedema: lymphatic obstruction after modified radical mastectomy and radiation</blockquote></li><li>(2) Filariasis due to Wuchereria bancrofti</li><li>(3) Scrotal and vulvar lymphedema due to lymphogranuloma venereum</li><li>(4) Breast lymphedema (inflammatory carcinoma) due to blockage of subcutaneous lymphatics by malignant cells (see <span>[[Fig. 21-39F|Figure 21-39]]</span>)</li> </ul> </ol><li>Increased synthesis of extracellular matrix components (e.g., glycosaminoglycans)</li><ol type="a"> <li>T-cell cytokines stimulate fibroblasts to synthesize glycosaminoglycans.</li><li>Example-pretibial myxedema and exophthalmos in Graves' disease (see <span>[[Fig. 22-11|Figure 22-11]]</span>)</li> </ol> </ol>
</div></html>
![[4.III.A.Types of edema fluid]]
<<tiddler [[4.III.A.Types of edema fluid]]>>
![[4.III.B.Pathophysiology of edema]]
<<tiddler [[4.III.B.Pathophysiology of edema]]>>
<html><a name="HC004018"></a> <br><a name="P004026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Endothelial cell injury
<blockquote style="color: blue; ">Endothelial cell injury: arterial thrombi</blockquote></li><ul> <li>Due to turbulent blood flow at arterial bifurcations or overlying atherosclerotic plaques; cigarette smoke</li> </ul><li>Stasis of blood flow
<blockquote style="color: blue; ">Stasis of blood flow: venous thrombi</blockquote></li><ul> <li>Sluggish blood flow due to prolonged bed rest or sitting (e.g., long airplane flight)</li> </ul><li>Hypercoagulability</li><ol type="a"> <li>Activation of coagulation system</li><li>Causes of hypercoagulability</li><ul> <li>(1) Hereditary or acquired factor deficiencies (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>)</li><ul> <li>Example-hereditary antithrombin III deficiency or acquired deficiency due to oral contraceptives</li> </ul><li>(2) Antiphospholipid syndrome (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>)</li><ul> <li>Due to lupus anticoagulant and/or anticardiolipin antibodies</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC004019"></a> <br><a name="P004027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Venous thrombi</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Stasis</li><ul> <li>(a) Procoagulants (e.g., tissue thromboplastin) released from damaged endothelium cause localized activation of the coagulation system.</li><li>(b) Fibrin is produced, which forms a mesh around RBCs, platelets, and white blood cells in the stagnant blood within the vessel to produce a thrombus.</li> </ul><li>(2) Hypercoagulable state</li> </ul><li>Sites</li><ul> <li>(1) Deep vein in the lower extremity below the knee
<blockquote style="color: blue; ">Most common site for venous thrombosis: deep vein in lower extremity below the knee</blockquote></li><li>(2) Other sites</li><ul> <li>Superficial saphenous, hepatic, and renal veins; dural sinuses</li> </ul> </ul><li>Composition</li><ul> <li>(1) Adherent, occlusive, dark red fibrin clot (see previous)</li><ul> <li>Contains entrapped RBCs (primary component), white blood cells, and platelets
<blockquote style="color: blue; ">Composition venous thrombus: entrapped RBCs, platelets, white blood cells</blockquote></li> </ul><li>(2) In the lower extremities, they propagate (extend) toward the heart.</li><ul> <li>Danger of pulmonary artery embolization once they reach the femoral vein</li> </ul> </ul><li>Anticoagulants heparin and warfarin prevent formation of venous thrombi (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>).</li><ul> <li>(1) Anticoagulants do not dissolve the thrombus; they only prevent further formation of a thrombus.</li><li>(2) The fibrinolytic system (plasmin) is responsible for dissolution of the thrombus.
<blockquote style="color: blue; ">Heparin and warfarin: anticoagulants that prevent venous thrombosis</blockquote></li> </ul> </ol><li>Arterial thrombi</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Endothelial cell injury due to turbulent blood flow</li><ul> <li>Platelets adhere to areas of injury.</li> </ul><li>(2) Hypercoagulable state</li> </ul><li>Sites</li><ul> <li>(1) Elastic and muscular arteries</li><li>(2) Majority of thrombi overlie disrupted atherosclerotic plaques</li><ul> <li>Example-coronary artery thrombosis (<span>[[Fig. 4-13|Figure 4-13]]</span>)</li> </ul> </ul><li>Composition of thrombi in muscular arteries and aortic branches
<blockquote style="color: blue; ">Composition of arterial thrombus: fibrin clot composed of platelets</blockquote></li><ul> <li>(1) Adherent, usually occlusive, gray-white fibrin clot composed of platelets</li><li>(2) Aspirin and other inhibitors of platelet aggregation prevent formation of these thrombi (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>).
<blockquote style="color: blue; ">Aspirin: prevents formation of arterial thrombi</blockquote></li> </ul><li>Composition of thrombi in the heart chambers and aorta</li><ul> <li>(1) Laminated thrombi with alternating pale and red areas (lines of Zahn)</li><ul> <li>(a) Pale areas are composed of platelets held together by fibrin.</li><li>(b) Red areas are composed predominantly of RBCs held together by fibrin.</li><li>(c) Mixed type of thrombus
<blockquote style="color: blue; ">Mixed thrombus: prevented by aspirin along with anticoagulant therapy</blockquote></li> </ul><li>(2) Examples of thrombi in the heart chambers</li><ul> <li>(a) Thrombus in left ventricle due to a transmural myocardial infarction (mural thrombus)</li><li>(b) Thrombus in left atrium in patients with mitral stenosis complicated by atrial fibrillation</li> </ul><li>(3) Thrombi in the aorta usually develop in aneurysms.</li><ul> <li>Example-abdominal aortic aneurysm (see <span>[[Fig. 9-4|Figure 9-4]]</span>)</li> </ul><li>(4) Aspirin along with anticoagulant therapy helps to prevent these types of mixed thrombi.</li> </ul><li>Clinical findings in arterial thrombosis</li><ul> <li>(1) Infarction (e.g., acute myocardial infarction, stroke)</li><li>(2) Embolization</li> </ul> </ol><li>Postmortem clot</li><ol type="a"> <li>Fibrin clot of plasma (resembles chicken fat) without entrapped cells</li><li>It is not attached to the vessel wall.</li> </ol> </ol>
</div></html>
![[4.IV.A.Pathogenesis of thrombi]]
<<tiddler [[4.IV.A.Pathogenesis of thrombi]]>>
![[4.IV.B.Types of thrombi]]
<<tiddler [[4.IV.B.Types of thrombi]]>>
<html><a name="HC004021"></a><span macro="tag [[16 Upper and Lower Respiratory Disorders]] [[Chapter 16]]"></span> <br> <br><a name="P004030"></a><div class="PA" style="color: black; "><ol type="1"> <li>Site of origin</li><ol type="a"> <li>Majority originate from the femoral vein (extension of deep vein thrombus).
<blockquote style="color: blue; ">Pulmonary thromboembolism: majority originate in femoral veins</blockquote></li><li>Others originate from the pelvic veins or vena cava.</li> </ol><li>Clinical findings</li><ol type="a"> <li>Sudden death</li><ul> <li>Due to a saddle embolus occluding the major pulmonary artery branches (see <span>[[Fig. 16-15|Figure 16-15]]</span>)</li> </ul><li>Pulmonary infarction</li><ul> <li>(1) Small thromboemboli occlude medium-sized or small pulmonary arteries (see <span>[[Fig. 1-11C|Figure 1-11]]</span>).</li><li>(2) Less than 10% of thromboemboli produce infarction.</li><ul> <li>Due to dual blood supply of the lungs: pulmonary artery, bronchial artery (refer to <span macro="tag [[16 Upper and Lower Respiratory Disorders]] [[Chapter 16]]"></span>)
<blockquote style="color: blue; ">Pulmonary infarction uncommon: due to dual blood supply-pulmonary arteries, bronchial arteries</blockquote></li> </ul> </ul><li>Paradoxic embolism</li><ul> <li>Venous thromboembolus passes through an atrial septal defect into the systemic circulation.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC004022"></a> <br><a name="P004031"></a><div class="PA" style="color: black; "><ul> <li>Emboli traveling in the arterial system</li><ol type="1"> <li>Causes of systemic embolism</li><ol type="a"> <li>Thrombi from the left side of the heart (80% of cases)
<blockquote style="color: blue; ">Systemic embolism: majority originate in left side of heart</blockquote></li><ul> <li>(1) Mural thrombus in left ventricle following acute myocardial infarction</li><li>(2) Thrombus in the left atrium in mitral stenosis</li><ul> <li>Atrial fibrillation predisposes to atrial clot formation and embolization.</li> </ul> </ul><li>Atrial myxoma, vegetations from aortic or mitral valve</li> </ol><li>Sites of embolism</li><ol type="a"> <li>Lower extremities (most common)</li><li>Brain (via the middle cerebral artery)</li><li>Small bowel (via the superior mesenteric artery)</li><li>Spleen and kidneys</li> </ol><li>Clinical findings</li><ol type="a"> <li>Pale infarctions in the digits, spleen, and kidneys</li><li>Hemorrhagic infarctions in the brain and small bowel (see <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>)</li> </ol> </ol> </ul>
</div></html>
<html><a name="HC004023"></a> <br><a name="P004032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Causes</li><ol type="a"> <li>Most often due to traumatic fracture of the long bones (e.g., femur) or pelvis
<blockquote style="color: blue; ">Fat embolism: fracture of long bones</blockquote></li><li>Other causes include trauma to fat-laden tissues (liposuction), fatty liver.</li> </ol><li>Pathogenesis</li><ol type="a"> <li>Microglobules of fat from the bone marrow gain access to the microvasculature.</li><li>Microglobules eventually obstruct the microvasculature in the brain, lungs, kidneys, and other sites.</li><ul> <li>Produces ischemia and hemorrhage</li> </ul><li>Fatty acids derived from breakdown of the microglobules damage vessel endothelium.</li><ul> <li>Platelet thrombi develop in areas of endothelial injury.</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Symptoms begin 24 to 72 hours after trauma.</li><li>Restlessness, delirium, coma</li><li>Dyspnea, tachypnea</li><ul> <li>(1) Fat microglobules in pulmonary capillaries cause hypoxemia.
<blockquote style="color: blue; ">Fat embolism: dyspnea, petechia over chest/upper extremities</blockquote></li><li>(2) Massive perfusion defect</li> </ul><li>Petechiae commonly develop over the chest and upper extremities.</li><ul> <li>Due to thrombocytopenia from platelet adhesion to microglobules of fat</li> </ul><li>Death results in less than 10% of cases.</li> </ol><li>Diagnosis</li><ol type="a"> <li>Usually a clinical diagnosis based on above findings</li><li>Search for fat globules in urine, pulmonary alveolar lavage, spinal fluid</li> </ol><li>Treatment is supportive</li><ul> <li>Maintain good arterial oxygenation</li> </ul> </ol>
</div></html>
<html><a name="HC004024"></a> <br><a name="P004033"></a><div class="PA" style="color: black; "><ol type="1"> <li>Occurs during labor or immediately post-partum</li><li>Pathogenesis</li><ol type="a"> <li>Tears in placental membranes or uterine veins</li><li>Infusion of amniotic fluid into the maternal circulation</li><ul> <li>Leads to cardiorespiratory collapse (? anaphylactic reaction to fetal antigens) and disseminated intravascular coagulation (procoagulants in AF)</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Abrupt onset of dyspnea, cyanosis, hypotension, and bleeding
<blockquote style="color: blue; ">Amniotic fluid embolism: abrupt onset dyspnea, hypotension, bleeding (DIC)</blockquote></li><ul> <li>(1) Dyspnea is due to pulmonary edema or acute respiratory distress syndrome.</li><li>(2) Bleeding is due to disseminated intravascular coagulation (DIC).</li> </ul><li>Diagnosis is most often confirmed at autopsy.</li><ul> <li>Fetal squamous cells are present in the pulmonary vessels.</li> </ul><li>Maternal mortality rate varies from 60% to 80%.</li><ul> <li>Most women who survive have permanent neurologic impairment.</li> </ul> </ol><li>Treatment is supportive.</li> </ol>
</div></html>
<html><a name="HC004025"></a> <br><a name="P004034"></a><div class="PA" style="color: black; "><ol type="1"> <li>Form of gas embolism</li><li>Scuba and deep sea diving is the most common cause.</li><li>Pathogenesis</li><ol type="a"> <li>Atmospheric pressure increases by 1 for every 33 feet of descent into water.</li><li>Nitrogen gas is forced out of the alveoli and dissolves in blood and tissues.</li><li>Rapid ascent causes nitrogen to expand and form gas bubbles in tissue and vessel lumens.
<blockquote style="color: blue; ">Decompression sickness: nitrogen gas bubbles occlude vessel lumens</blockquote></li> </ol><li>Clinical findings</li><ol type="a"> <li>Pain develops in joints, muscles, and bones.</li><ul> <li>Called "the bends"</li> </ul><li>Pneumothorax (refer to <span macro="tag [[16 Upper and Lower Respiratory Disorders]] [[Chapter 16]]"></span>)</li><ul> <li>(1) Complication of a sudden rise to the surface</li><li>(2) Due to rupture of a preexisting subpleural or intrapleural bleb</li><li>(3) Causes dyspnea and pleuritic chest pain</li> </ul><li>Pulmonary embolus</li><ul> <li>(1) Pressure on the veins in the lower extremities produces stasis and thrombus formation.</li><li>(2) Pulmonary thromboembolism occurs
<blockquote style="color: blue; ">Pneumothorax, pulmonary embolism, aseptic necrosis: complications of scuba diving</blockquote></li><li>(3) Causes dyspnea and pleuritic chest pain</li> </ul><li>Chronic changes</li><ul> <li>Aseptic necrosis in bones (femur, tibia, humerus) from bone infarctions</li> </ul> </ol><li>Treatment</li><ul> <li>Recompression (nitrogen forced back into tissue) followed by slow decompression</li> </ul> </ol>
</div></html>
![[4.V.A.Pulmonary thromboembolism (refer to Chapter 16)]]
<<tiddler [[4.V.A.Pulmonary thromboembolism (refer to Chapter 16)]]>>
![[4.V.B.Systemic embolism]]
<<tiddler [[4.V.B.Systemic embolism]]>>
![[4.V.C.Fat embolism]]
<<tiddler [[4.V.C.Fat embolism]]>>
![[4.V.D.Amniotic fluid (AF) embolism]]
<<tiddler [[4.V.D.Amniotic fluid (AF) embolism]]>>
![[4.V.E.Decompression sickness]]
<<tiddler [[4.V.E.Decompression sickness]]>>
<html><a name="HC004027"></a> <br><a name="P004036"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hypovolemic shock
<blockquote style="color: blue; ">Hypovolemic shock: most often caused by blood loss</blockquote></li><ol type="a"> <li>Due to excessive fluid loss (e.g., blood, sweat)</li><li>Hemorrhage</li><ul> <li>(1) Loss of greater than 20% of blood volume (∼1000 mL) results in shock.</li><li>(2) No initial effect on hemoglobin and hematocrit concentration</li><ul> <li>(a) Absolute neutrophilic leukocytosis is the first hematologic sign.</li><li>(b) Infusion of 0.9% saline immediately uncovers the RBC deficit.</li> </ul><li>(3) Plasma is replaced first with fluid from the interstitial space.</li><ul> <li>Uncovers the RBC deficit within hours to days</li> </ul><li>(4) RBC response in the bone marrow begins in 5 to 7 days.</li> </ul><li>Pathophysiology of hypovolemic shock</li><ul> <li>(1) Decreased cardiac output (CO)</li><ul> <li>Due to decreased volume of blood</li> </ul><li>(2) Decreased left ventricular end-diastolic pressure (LVEDP)</li><li>(3) Increased peripheral vascular resistance (PVR)</li><ul> <li>Due to vasoconstriction of arterioles from catecholamines, ADH, and angiotensin II, which are released in response to the decreased CO</li> </ul><li>(4) Decreased mixed venous oxygen content (MVO<sub>2</sub>)</li><ul> <li>(a) Best indicator of tissue hypoxia
<blockquote style="color: blue; ">MVO<sub>2</sub>: best indicator of tissue hypoxia</blockquote></li><li>(b) Measured in the right side of the heart with a Swan-Ganz catheter</li><li>(c) Indicates the degree of extraction of O<sub>2</sub> from the blood delivered to tissue</li><li>(d) In hypovolemic shock, decreased blood flow through the microcirculation leads to increased extraction of O<sub>2</sub> from the blood and a decreased MVO<sub>2</sub>.
<blockquote style="color: blue; ">Hypovolemic shock: ↓CO, ↓LVEDP, ↑PVR, ↓MVO<sub>2</sub></blockquote></li> </ul> </ul><li>Clinical findings in hypovolemic shock</li><ul> <li>(1) Cold, clammy skin due to vasoconstriction of skin vessels</li><li>(2) Hypotension; rapid, weak pulse (compensatory response to decreased CO)</li> </ul> </ol><li>Cardiogenic shock</li><ol type="a"> <li>Most commonly caused by an acute myocardial infarction
<blockquote style="color: blue; ">Cardiogenic shock: most often caused by acute myocardial infarction</blockquote></li><li>Pathophysiology of cardiogenic shock</li><ul> <li>(1) Decreased CO</li><ul> <li>Due to decreased force of contraction in the left ventricle</li> </ul><li>(2) Increased LVEDP</li><ul> <li>Blood accumulates in the left ventricle.</li> </ul><li>(3) Increased PVR</li><ul> <li>Same mechanism as in hypovolemic shock</li> </ul><li>(4) Decreased MVO<sub>2</sub></li><ul> <li>Same mechanism as in hypovolemic shock</li> </ul> </ul><li>Clinical findings in cardiogenic shock</li><ul> <li>Chest pain followed by signs similar to hypovolemic shock</li> </ul> </ol><li>Septic shock
<blockquote style="color: blue; ">Cardiogenic shock: ↓CO, ↑LVEDP, ↑PVR, ↓MVO<sub>2</sub></blockquote></li><ol type="a"> <li>Septicemia is most commonly due to gram-negative pathogens (e.g., Escherichia coli).</li><li>Pathogenesis
<blockquote style="color: blue; ">Septic shock: most often caused by sepsis due to <i>E. coli</i></blockquote></li><ul> <li>(1) Endotoxins damage endothelial cells.</li><ul> <li>Causes the release of vasodilators such as nitric oxide and prostaglandin I<sub>2</sub></li> </ul><li>(2) Endotoxins activate the alternative complement pathway.</li><ul> <li>Anaphylatoxins (C3a and C5a) are produced, which stimulate mast cell release of histamine (vasodilator)</li> </ul><li>(3) Interleukin 1 and tumor necrosis factor (TNF) are released from macrophages.</li><ul> <li>(a) Activate neutrophil adhesion molecules, causing neutrophil adherence to pulmonary capillaries</li><li>(b) Circulating neutrophil pool becomes part of the marginating neutrophil pool (refer to <span macro="tag [[02 Inflammation and Repair]] [[Chapter 2]]"></span>).</li><li>(c) High levels of TNF contribute to the vascular leakage syndrome.</li><ul> <li>Important in the pathophysiology of acute respiratory distress syndrome</li> </ul> </ul> </ul><li>Pathophysiology of septic shock</li><ul> <li>(1) Initial increase in CO</li><ul> <li>Due to rapid blood flow through dilated peripheral resistance arterioles, causing increased return of blood to the heart</li> </ul><li>(2) Decreased LVEDP</li><ul> <li>Due to neutrophil transmigration through the pulmonary capillaries into alveoli producing noncardiogenic pulmonary edema</li> </ul><li>(3) Decreased PVR</li><ul> <li>Due to vasodilation of peripheral resistance arterioles</li> </ul><li>(4) Increased MVO<sub>2</sub></li><ul> <li>Tissues are unable to extract O<sub>2</sub>, because of the increased blood flow.
<blockquote style="color: blue; ">Septic shock (initial phase): ↑CO, ↓LVEDP, ↓PVR, ↑MVO<sub>2</sub></blockquote></li> </ul> </ul><li>Clinical findings in septic shock</li><ul> <li>(1) Warm skin, due to vasodilation of skin vessels</li><li>(2) Bounding pulse, due to increased CO</li><li>(3) Acute respiratory distress syndrome</li><ul> <li>Due to neutrophil transmigration into alveoli</li> </ul><li>(4) Disseminated intravascular coagulation</li><ul> <li>Due to activation of the intrinsic and extrinsic coagulation system</li> </ul> </ul> </ol><li>Summary of pathophysiologic findings in shock (<span>[[Table 4-11|Table 4-11. SUMMARY OF PATHOPHYSIOLOGIC FINDINGS IN HYPOVOLEMIC, CARDIOGENIC, AND SEPTIC SHOCK]]</span>)</li> </ol>
</div></html>
<html><a name="HC004028"></a> <br><a name="P004037"></a><div class="PA" style="color: black; "><ol type="1"> <li>Ischemic acute tubular necrosis</li><ul> <li>Coagulation necrosis of proximal tubule cells and cells in the thick ascending limb</li> </ul><li>Multiorgan dysfunction
<blockquote style="color: blue; ">Multiorgan dysfunction: most common cause of death in shock</blockquote></li><ul> <li>Most common cause of death</li> </ul><li>Lactic acidosis due to tissue hypoxia</li> </ol>
</div></html>
![[4.VI.A.Types of shock]]
<<tiddler [[4.VI.A.Types of shock]]>>
![[4.VI.B.Complications associated with shock]]
<<tiddler [[4.VI.B.Complications associated with shock]]>>
<html><a name="HC005002"></a> <br><a name="PB005001"></a><div class="BB" style="color: rgb(47, 79, 79); ">In both <b>sickle cell trait</b> and <b>sickle cell disease</b>, a missense mutation occurs when adenine replaces thymidine, causing valine to replace glutamic acid in the sixth position of the β-globin chain. As a result, RBCs spontaneously sickle in the peripheral blood if the amount of sickle hemoglobin is greater than 60%.</div><a name="P005002"></a><div class="PA" style="color: black; "><ul> <li>Mutation involving a change in a single nucleotide base within a gene</li><ol type="1"> <li>Silent mutation (<span>[[Fig. 5-1A|Figure 5-1]]</span>)</li><ul> <li>Altered DNA codes for the <i>same</i> amino acid without changing the phenotypic effect</li> </ul><li>Missense mutation (<span>[[Fig. 5-1B|Figure 5-1]]</span>)
<blockquote style="color: blue; ">Missense mutation: sickle cell disease/trait</blockquote></li><ul> <li>Altered DNA codes for a <i>different</i> amino acid, which changes the phenotypic effect
<blockquote style="color: blue; ">β-Thalassemia major: nonsense mutation with stop codon</blockquote></li> </ul><li>Nonsense mutation (<span>[[Fig. 5-1C|Figure 5-1]]</span>)</li><ul> <li>Altered DNA codes for a stop codon that causes premature termination of protein synthesis</li> </ul> </ol> </ul>
</div><a name="PB005002"></a><div class="BB" style="color: rgb(47, 79, 79); ">In <b>β-thalassemia major</b>, a nonsense mutation produces a stop codon that causes premature termination of DNA transcription of the β-globin chain. Consequently, there is no synthesis of hemoglobin A (α<sub>2</sub>β<sub>2</sub>), resulting in a microcytic anemia.</div></html>
<html><a name="HC005003"></a> <br><a name="P005003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Insertion or deletion of one or more nucleotides shifts the reading frame of the DNA strand
<blockquote style="color: blue; ">Frameshift mutation: Tay-Sachs disease</blockquote></li><li>Example-in Tay-Sachs disease, a four-base insertion results in an altered DNA code leading to formation of a stop codon leading to decreased synthesis of hexosaminidase (<span>[[Fig. 5-2|Figure 5-2]]</span>).</li> </ol>
</div></html>
<html><a name="HC005004"></a> <br><a name="P005004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Errors in DNA replication</li><ul> <li>Cause amplification of a sequence of three nucleotides (e.g., CAG), which disrupts gene function</li> </ul><li>Associated with anticipation
<blockquote style="color: blue; ">Anticipation: additional trinucleotide repeats increase disease severity in future generations</blockquote></li><ol type="a"> <li>Increasing severity of clinical disease in each successive generation</li><li>Caused by the addition of more trinucleotide sequences during gametogenesis</li><li>Female carriers may be symptomatic</li><ul> <li>Occurs if they have more paternally (than maternally) derived X chromosomes with trinucleotide repeats</li> </ul><li>Examples-fragile X syndrome, Huntington's disease, Friedreich's ataxia, myotonic dystrophy</li> </ol> </ol>
</div></html>
![[5.I.A.Point mutations]]
<<tiddler [[5.I.A.Point mutations]]>>
![[5.I.B.Frameshift mutation]]
<<tiddler [[5.I.B.Frameshift mutation]]>>
![[5.I.C.Trinucleotide repeat disorders]]
<<tiddler [[5.I.C.Trinucleotide repeat disorders]]>>
<html><a name="HC005006"></a> <br><a name="PB005003"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Cystic fibrosis (CF)</b> is an AR disorder with a carrier rate of 1/25. To calculate the prevalence of CF in the population, the number of couples at risk of having a child with CF (1/25 × 1/25, or 1/625) is multiplied by the chance of having a child with CF (1/4). Prevalence of CF = 1/625 × 1/4, or 1/2500. Note how it is possible to calculate the carrier rate if given the prevalence of the disease by dividing 1/2500 by 4 to get the number of couples at risk and then taking the square root of 1/625 to get the carrier rate of 1/25.</div><a name="PB005004"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Phenylketonuria</b> (PKU, see <span>[[Fig. 5-4|Figure 5-4]]</span>) is characterized by a deficiency of phenylalanine hydroxylase, causing an increase in the substrate phenylalanine and a decrease in the product tyrosine. In individuals with PKU, phenylalanine is further metabolized into neurotoxic phenylketones and acids that produce mental retardation and urine with a musty odor.</div><a name="P005006"></a><div class="PA" style="color: black; "><ol type="1"> <li>Inheritance pattern (<span>[[Fig. 5-3|Figure 5-3]]</span>)
<blockquote style="color: blue; ">Most common type of mendelian disorder: autosomal recessive</blockquote></li><ol type="a"> <li>Individuals must be homozygous for the mutant recessive gene (aa) to express the disorder.</li><li>Homozygotes are symptomatic early in life.</li><li>Heterozygous individuals (Aa) are asymptomatic carriers.</li><ul> <li>The dominant gene (A) overrides the mutant recessive gene (a).</li> </ul><li>Both parents must be heterozygous to transmit the disorder.
<blockquote style="color: blue; ">AR inheritance: both parents must have mutant gene.</blockquote></li><ul> <li>Example-Aa × Aa → AA, Aa, Aa, aa (25% without disorder; 50% asymptomatic carriers; 25% with disorder)</li> </ul> </ol><li>AR protein defects (<span>[[Table 5-1|Table 5-1. PROTEIN DEFECTS ASSOCIATED WITH SELECTED MENDELIAN DISORDERS]]</span>)
<blockquote style="color: blue; ">Most AR disorders involve enzyme deficiencies.</blockquote></li><li>Inborn errors of metabolism (<span>[[Figs. 5-4|Figure 5-4]]</span> to <span>[[5-7|Figure 5-7]]</span> and <span>[[Table 5-2|Table 5-3. SELECTED LYSOSOMAL STORAGE DISORDERS]]</span>)</li><ol type="a"> <li>Most metabolic disorders are due to an enzyme deficiency.</li><li>Substrate and intermediates proximal to the enzyme block increase.</li><li>Intermediates and the end-product distal to the enzyme block decrease.</li><li>Glycogenoses
<blockquote style="color: blue; ">PKU: ↑phenylalanine, ↓ tyrosine</blockquote></li><ul> <li>(1) Pathogenesis</li><ul> <li>(a) Increase in glycogen synthesis (e.g., von Gierke's disease)
<blockquote style="color: blue; ">Von Gierke's disease: glucose-6-phosphatase deficiency (gluconeogenic enzyme)</blockquote></li><li>(b) Inhibition of glycogenolysis (e.g., debranching enzyme deficiency)</li><li>(c) Increase in normal or structurally abnormal glycogen</li> </ul><li>(2) Clinical findings</li><ul> <li>(a) Organ dysfunction (e.g., restrictive heart disease, Pompe's disease).</li><li>(b) Fasting hypoglycemia</li><ul> <li>Decrease in gluconeogenesis (e.g., glucose-6-phosphatase deficiency, von Gierke's disease) or liver glycogenolysis (e.g., liver phosphorylase deficiency)</li> </ul> </ul> </ul><li>Lysosomal storage diseases (<span>[[Table 5-3|Table 5-3. SELECTED LYSOSOMAL STORAGE DISORDERS]]</span> and <span>[[Figs. 5-8|Figure 5-8]]</span> and <span>[[5-9|Figure 5-9]]</span>)</li><ul> <li>Enzyme deficiencies lead to accumulation of undigested substrates (e.g., glycosaminoglycans, sphingolipids) in lysosomes
<blockquote style="color: blue; ">Most common AR disorder: hemochromatosis</blockquote></li> </ul> </ol><li>Other AR disorders</li><ul> <li>Hematochromatosis, 21-hydroxylase deficiency, Wilson's disease, thalassemia</li> </ul> </ol>
</div></html>
<html><a name="HC005007"></a> <br><a name="P005007"></a><div class="PA" style="color: black; "><ol type="1"> <li>Inheritance pattern</li><ol type="a"> <li>One dominant mutant gene (A) is required to express the disorder.
<blockquote style="color: blue; ">AD inheritance: heterozygotes with dominant mutant gene express disease</blockquote></li><ul> <li>(1) Heterozygotes (Aa) express the disorder.</li><li>(2) Homozygotes (AA) are often spontaneously aborted.</li><li>(3) Example-Aa × aa → Aa, Aa, aa, aa (50% with disorder; 50% without disorder)</li> </ul><li>Some disorders arise by new mutations involving either an egg or a sperm.</li> </ol><li>AD protein defects (see <span>[[Table 5-1|Table 5-1. PROTEIN DEFECTS ASSOCIATED WITH SELECTED MENDELIAN DISORDERS]]</span>)</li><ul> <li>Enzyme deficiencies are relatively uncommon.</li> </ul><li>Characteristics</li><ol type="a"> <li>Delayed manifestations of disease</li><ul> <li>(1) Symptoms and signs may <i>not</i> occur early in life.</li><li>(2) Example-in adult polycystic kidney disease, cysts are <i>not</i> present at birth.</li> </ul><li>Penetrance</li><ul> <li>(1) Complete penetrance (<span>[[Fig. 5-10A|Figure 5-10]]</span>)</li><ul> <li>All individuals with the mutant gene express the disorder (e.g., familial polyposis).</li> </ul><li>(2) Reduced penetrance (<span>[[Fig. 5-10B|Figure 5-10]]</span>)
<blockquote style="color: blue; ">Reduced penetrance: individual with mutant gene does <i>not</i> express the disease; transmits to children</blockquote></li><ul> <li>(a) Individuals with the mutant gene are phenotypically normal.</li><li>(b) They transmit the disorder to their offspring (e.g., Marfan syndrome; see <span>[[Fig. 9-6A|Figure 9-6]]</span>).</li> </ul> </ul><li>Variable expressivity</li><ul> <li>All individuals with the mutant gene express the disorder but at different levels of severity.</li> </ul> </ol><li>Other AD disorders
<blockquote style="color: blue; ">Most common AD disorder: von Willebrand disease</blockquote></li><ul> <li>Huntington's disease, osteogenesis imperfecta, achondroplasia, tuberous sclerosis</li> </ul> </ol>
</div></html>
<html><a name="HC005008"></a> <br><a name="P005008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Inheritance pattern (<span>[[Fig. 5-11|Figure 5-11]]</span>)</li><ol type="a"> <li>Males must have the mutant recessive gene on the X chromosome to express the disorder.</li><li>Affected males (XY) transmit the mutant gene to all of their daughters.</li><ul> <li>(1) Males are homozygous for the mutant gene.</li><li>(2) Example-<u>X</u>Y × XX → <u>X</u>X, <u>X</u>X, XY, XY</li><li>(3) Daughters (<u>X</u>X) are usually asymptomatic carriers.</li> </ul><li>Asymptomatic female carriers (<u>X</u> mutant gene) transmit the disorder to 50% of their male offspring.</li><ul> <li>Example-<u>X</u>X × XY → <u>X</u>X, XX, <u>X</u>Y, XY
<blockquote style="color: blue; ">XR inheritance: asymptomatic female carrier transmits mutant gene to 50% of sons</blockquote></li> </ul><li>In rare cases, female carriers can be symptomatic.</li><ul> <li>(1) Maternally derived X chromosomes (without the mutant gene) are preferentially inactivated.</li><ul> <li>Only paternally derived X chromosomes with the mutant gene remain.</li> </ul><li>(2) Offspring of a symptomatic male and asymptomatic female carrier</li><ul> <li>Example-<u>X</u>X × <u>X</u>Y → <u>X</u>X, <u>X</u>X, <u>X</u>Y, XY</li> </ul> </ul><li>Some XR disorders may arise as new mutations.</li> </ol><li>XR protein defects (see <span>[[Table 5-1|Table 5-1. PROTEIN DEFECTS ASSOCIATED WITH SELECTED MENDELIAN DISORDERS]]</span>)</li><ul> <li>Enzymes are the most common type of protein affected in XR disorders.</li> </ul><li>Fragile X syndrome</li><ol type="a"> <li>Trinucleotide repeat disorder</li><li>Clinical findings</li><ul> <li>(1) Mental retardation</li><ul> <li>(a) Most common mendelian disorder that causes mental retardation
<blockquote style="color: blue; ">Most common X-linked disorder: fragile X syndrome</blockquote></li><li>(b) 50% of female carriers may develop mental retardation.</li> </ul><li>(2) Phenotypic changes</li><ul> <li>Long face, large mandible, everted ears</li> </ul><li>(3) Macro-orchidism (enlarged testes) at puberty</li><li>(4) Diagnosis</li><ul> <li>(a) DNA analysis to identify trinucleotide repeats (best test)</li><li>(b) Fragile X chromosome study</li> </ul> </ul> </ol><li>Lesch-Nyhan syndrome</li><ol type="a"> <li>Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)</li><ul> <li>Normally involved in salvaging the purines hypoxanthine and guanine</li> </ul><li>Clinical findings</li><ul> <li>Mental retardation, hyperuricemia, self-mutilation</li> </ul> </ol><li>Other XR disorders</li><ul> <li>Testicular feminization, chronic granulomatous disease, Bruton's agammaglobulinemia</li> </ul> </ol>
</div></html>
<html><a name="HC005009"></a> <br><a name="P005009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Inheritance pattern</li><ul> <li>Same as XR <i>except</i> the dominant mutant gene causes disease in males and females (<span>[[Fig. 5-12|Figure 5-12]]</span>)
<blockquote style="color: blue; ">XD inheritance: female carriers are symptomatic</blockquote></li> </ul><li>Vitamin D-resistant rickets</li><ol type="a"> <li>Defect in renal and gastrointestinal reabsorption of phosphate</li><li>Causes defective bone mineralization (i.e., osteomalacia)</li> </ol><li>Alport's syndrome</li><ul> <li>Hereditary glomerulonephritis with nerve deafness</li> </ul> </ol>
</div></html>
![[5.II.A.Autosomal recessive (AR) disorders]]
<<tiddler [[5.II.A.Autosomal recessive (AR) disorders]]>>
![[5.II.B.Autosomal dominant (AD) disorders]]
<<tiddler [[5.II.B.Autosomal dominant (AD) disorders]]>>
![[5.II.C.X-linked recessive (XR) disorders]]
<<tiddler [[5.II.C.X-linked recessive (XR) disorders]]>>
![[5.II.D.X-linked dominant (XD) disorders]]
<<tiddler [[5.II.D.X-linked dominant (XD) disorders]]>>
<html><a name="HC005011"></a> <br><a name="P005023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Most human cells are diploid (46 chromosomes).</li><ol type="a"> <li>Autosomes: 22 pairs</li><li>Sex chromosomes (XX in females and XY in males): 1 pair</li> </ol><li>Gametes, the products of meiosis, are haploid (23 chromosomes).</li><li>Lyon hypothesis</li><ol type="a"> <li>In females, one of the two X chromosomes is randomly inactivated.
<blockquote style="color: blue; ">Barr body: inactivated</blockquote></li><ul> <li>Inactivation occurs in the embryonic period of development.</li> </ul><li>The inactivated X chromosome is called a Barr body.</li><ul> <li>(1) The Barr body is attached to the nuclear membrane of cells.
<blockquote style="color: blue; ">Barr body: attached to nuclear membrane</blockquote></li><li>(2) They are visible in squamous cells obtained by scraping the buccal mucosa.</li> </ul><li>Normal females have one Barr body, and normal males have none.
<blockquote style="color: blue; ">Number of Barr bodies = number of X chromosomes - 1</blockquote></li><li>Inactivation accounts for the parental derivation of the X chromosomes in females.</li><ul> <li>∼50% of X chromosomes are paternal and ∼50% are maternal.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC005012"></a> <br><a name="PB005005"></a><div class="BB" style="color: rgb(47, 79, 79); ">In one type of <b>Down syndrome</b>, the mother of an affected child has 45 (not 46) chromosomes because of a robertsonian translocation between the long arms of chromosomes 21 and 14. This produces one long chromosome (14;21). The mother also has one chromosome 14 and one chromosome 21. The father has the normal 46 chromosomes. The affected child has 46 chromosomes with three functional 21 chromosomes including chromosome (14;21) and chromosome 21 from the mother and chromosome 14 and chromosome 21 from the father (<span>[[Fig. 5-14|Figure 5-14]]</span>).</div><a name="P005024"></a><div class="PA" style="color: black; "><ul> <li>Numeric or structural abnormalities of autosomes or sex chromosomes</li><ol type="1"> <li>Nondisjunction</li><ol type="a"> <li>Unequal separation of chromosomes in the first phase of meiosis
<blockquote style="color: blue; ">Nondisjunction: unequal separation of chromosomes in meiosis</blockquote></li><li>Results in 22 or 24 chromosomes in the egg or sperm</li> </ol><li>Examples-Turner's syndrome (22 + 23 = 45 chromosomes), Down syndrome (24 + 23 = 47 chromosomes, trisomy; <span>[[Fig. 5-13|Figure 5-13]]</span>)</li><li>Mosaicism</li><ol type="a"> <li>Nondisjunction of chromosomes during mitotic division in the early embryonic period
<blockquote style="color: blue; ">Mosaicism: nondisjunction in mitosis</blockquote></li><li>Two chromosomally different cell lines are derived from a single fertilized egg.</li><li>Most often involves sex chromosomes (e.g., Turner's syndrome)</li> </ol><li>Translocation</li><ol type="a"> <li>Transfer of chromosome parts between nonhomologous chromosomes</li><li>Balanced translocation</li><ul> <li>Translocated fragment is functional.</li> </ul><li>Robertsonian translocation</li><ul> <li>Balanced translocation between two acrocentric chromosomes (e.g., chromosomes 14 and 21)</li> </ul> </ol><li>Deletion</li><ol type="a"> <li>Loss of a portion of a chromosome</li><li>Cri du chat syndrome
<blockquote style="color: blue; ">Cri du chat syndrome: deletion short arm chromosome 5</blockquote></li><ul> <li>(1) Loss of the short arm of chromosome 5</li><li>(2) Clinical findings</li><ul> <li>Mental retardation, cat-like cry, ventricular septal defect</li> </ul> </ul> </ol> </ol> </ul>
</div></html>
<html><a name="HC005013"></a> <br><a name="P005025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Down syndrome
<blockquote style="color: blue; ">Down syndrome: most cases due to nondisjunction</blockquote></li><ol type="a"> <li>Causes</li><ul> <li>(1) Nondisjunction (95% of cases, trisomy 21)</li><li>(2) Robertsonian translocation (4% of cases)</li><li>(3) Mosaicism (1% of cases)</li> </ul> </ol><li>Risk factors</li><ol type="a"> <li>Increased maternal age is a risk factor.
<blockquote style="color: blue; ">Advanced maternal age: increased risk for bearing offspring with trisomy syndromes</blockquote></li><li>Occurs in 1 in 25 live births in women over 45 years of age</li><li>Clinical findings</li><ul> <li>(1) General</li><ul> <li>(a) Most common genetic cause of mental retardation
<blockquote style="color: blue; ">Most common genetic cause of mental retardation: Down syndrome</blockquote></li><li>(b) Epicanthic folds, flat facial profile, macroglossia (<span>[[Fig. 5-15A|Figure 5-15]]</span>)</li><li>(c) Simian crease (<span>[[Fig. 5-15B|Figure 5-15]]</span>)</li> </ul><li>(2) Combined atrial and ventricular septal defects (cushion defects)</li><ul> <li>Major factor affecting survival in early childhood</li> </ul><li>(3) Increased risk of Hirschsprung's disease and duodenal atresia
<blockquote style="color: blue; ">Down syndrome: duodenal atresia, Hirschsprung's</blockquote></li><li>(4) Increased risk of leukemia</li><ul> <li>Acute lymphoblastic leukemia most commonly</li> </ul><li>(5) Alzheimer's disease by 35 years of age in most cases
<blockquote style="color: blue; ">Down syndrome: Alzheimer's disease at young age</blockquote></li><ul> <li>Major factor affecting survival in older individuals</li> </ul><li>(6) Sterility in all males</li><li>(7) Females have a 50% chance of having a child with Down syndrome.</li> </ul> </ol><li>Edwards' syndrome
<blockquote style="color: blue; ">Edward's syndrome: trisomy 18</blockquote></li><ol type="a"> <li>Trisomy 18</li><li>Clinical findings</li><ul> <li>(1) Mental retardation</li><li>(2) Clenched hands with overlapping fingers</li><li>(3) Ventricular septal defect (VSD)</li><li>(4) Early death</li> </ul> </ol><li>Patau's syndrome
<blockquote style="color: blue; ">Patau's syndrome: trisomy 13</blockquote></li><ol type="a"> <li>Trisomy 13</li><li>Clinical findings</li><ul> <li>(1) Mental retardation</li><li>(2) Cleft lip and palate</li><li>(3) Polydactyly, VSD, cystic kidneys</li><li>(4) Early death</li> </ul> </ol> </ol>
</div></html>
![[5.III.A.General considerations]]
<<tiddler [[5.III.A.General considerations]]>>
![[5.III.B.Chromosomal alterations]]
<<tiddler [[5.III.B.Chromosomal alterations]]>>
![[5.III.C.Disorders involving autosomes]]
<<tiddler [[5.III.C.Disorders involving autosomes]]>>
![[5.III.D.Disorders involving sex chromosomes]]
<<tiddler [[5.III.D.Disorders involving sex chromosomes]]>>
<html><a name="HC005014"></a> <br><a name="P005026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Turner's syndrome</li><ol type="a"> <li>Causes</li><ul> <li>(1) Nondisjunction</li><ul> <li>45,X karyotype (∼60% of cases)
<blockquote style="color: blue; ">Turner's syndrome: 45,X karyotype</blockquote></li> </ul><li>(2) Mosaicism</li><ul> <li>45,X/46,XX karyotype (∼40% of cases)</li> </ul> </ul><li>Clinical and laboratory findings</li><ul> <li>(1) Short stature</li><ul> <li>(a) Cardinal finding</li><li>(b) Normal growth hormone and insulin-like growth factor</li> </ul><li>(2) Lymphedema in hands and feet in infancy</li><ul> <li>Webbed neck is caused by dilated lymphatic channels (cystic hygroma) (<span>[[Fig. 5-16|Figure 5-16]]</span>).
<blockquote style="color: blue; ">Webbed neck: cystic hygroma</blockquote></li> </ul><li>(3) Preductal coarctation and bicuspid aortic valve</li><li>(4) Streak gonads</li><ul> <li>(a) Ovaries replaced by fibrous stroma</li><li>(b) Ovaries devoid of oocytes by 2 years of age
<blockquote style="color: blue; ">Turner's syndrome: "menopause before menarche"</blockquote></li><ul> <li>All patients with a 45,X karyotype are infertile.</li> </ul><li>(c) Increased risk for developing ovarian dysgerminoma</li> </ul><li>(5) Primary amenorrhea with delayed sexual maturation
<blockquote style="color: blue; ">Most common genetic cause of primary amenorrhea: Turner's syndrome</blockquote></li><ul> <li>(a) Decreased estradiol and progesterone</li><li>(b) Increased follicle-stimulating hormone (FSH) and luteinizing hormone (LH)</li> </ul><li>(6) Normal intelligence, horseshoe kidney, hypothyroidism</li><li>(7) No Barr bodies</li> </ul> </ol><li>Klinefelter's syndrome</li><ol type="a"> <li>Cause</li><ul> <li>(1) Nondisjunction</li><li>(2) XXY karyotype</li> </ul><li>Clinical and laboratory findings (<span>[[Fig. 5-17|Figure 5-17]]</span>)</li><ul> <li>(1) Female secondary sex characteristics at puberty</li><ul> <li>(a) Persistent gynecomastia</li><li>(b) Soft skin</li><li>(c) Female hair distribution</li> </ul><li>(2) Delayed sexual maturation (hypogonadism)</li><ul> <li>(a) Testicular atrophy (decreased testicular volume)</li><li>(b) Fibrosis of seminiferous tubules</li><ul> <li>Absence of spermatogenesis (azoospermia); loss of Sertoli cells</li> </ul><li>(c) Leydig cell hyperplasia</li> </ul><li>(3) Disproportionately long legs, learning disabilities
<blockquote style="color: blue; ">Klinefelter's syndrome: ↓ testosterone and inhibin; ↑LH and FSH, respectively</blockquote></li><li>(4) Decreased inhibin (loss of Sertoli cells)</li><ul> <li>(a) Causes increased FSH (loss of negative feedback with inhibin)</li><li>(b) Increased FSH causes increased synthesis of aromatase in Leydig cells.</li> </ul><li>(5) Decreased testosterone</li><ul> <li>(a) Aromatase converts testosterone to estradiol; estradiol causes feminization.</li><li>(b) Increased LH (loss of negative feedback with testosterone)</li> </ul><li>(6) One Barr body</li> </ul> </ol><li>XYY syndrome
<blockquote style="color: blue; ">XYY syndrome: paternal nondysjunction; aggressive behavior</blockquote></li><ol type="a"> <li>Caused by paternal nondisjunction</li><li>Associated with aggressive (sometimes criminal) behavior</li><li>Normal gonadal function</li> </ol> </ol>
</div></html>
<html><a name="HC005016"></a> <br><a name="P005031"></a><div class="PA" style="color: black; "><ol type="1"> <li>Combination of multiple minor gene mutations plus environmental factors
<blockquote style="color: blue; ">Polygenic disorders are more common than mendelian and chromosomal disorders.</blockquote></li><li>Examples of multifactorial inheritance</li><ol type="a"> <li>Open neural tube defects</li><ul> <li>Associated with decreased maternal folate levels</li> </ul><li>Type 2 diabetes mellitus</li><ul> <li>Associated with obesity, which downregulates insulin receptor synthesis</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC005017"></a><span>[[Fig. 5-18|Figure 5-18]]</span> <br> <br><a name="P005032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Function of mitochondrial DNA</li><ul> <li>Codes for enzymes involved in mitochondrial oxidative phosphorylation reactions
<blockquote style="color: blue; ">Mitochondrial DNA disorders: associated with maternal inheritance; ova have mutant gene</blockquote></li> </ul><li>Inheritance pattern</li><ol type="a"> <li>Affected females transmit the mutant gene to all their children.</li><ul> <li>Ova contain mitochondria with the mutant gene.</li> </ul><li>Affected males do <i>not</i> transmit the mutant gene to any of their children.</li><ul> <li>Sperm lose their mitochondria during fertilization.</li> </ul> </ol><li>Examples-Leber's hereditary optic neuropathy, myoclonic epilepsy</li> </ol>
</div></html>
<html><a name="HC005018"></a> <br><a name="P005033"></a><div class="PA" style="color: black; "><ol type="1"> <li>Inheritance pattern</li><ol type="a"> <li>Inheritance depends on whether the mutant gene is of maternal or paternal origin.
<blockquote style="color: blue; ">Genomic imprinting: inheritance depends whether mutant gene of maternal or paternal origin</blockquote></li><li>Examples-Prader-Willi syndrome and Angelman syndrome</li> </ol><li>Pathogenesis (<span>[[Fig. 5-19|Figure 5-19]]</span>)</li><ol type="a"> <li>Normal changes in maternal chromosome 15 during gametogenesis</li><ul> <li>(1) Prader-Willi gene is inactivated by methylation (imprinted).</li><li>(2) Angelman gene is demethylated (activated).</li> </ul><li>Normal changes in paternal chromosome 15 during gametogenesis</li><ul> <li>(1) Prader-Willi gene is demethylated (activated).</li><li>(2) Angelman gene is imprinted (inactivated).</li> </ul><li>Microdeletion of the entire gene site on paternal chromosome 15</li><ul> <li>(1) Causes Prader-Willi syndrome
<blockquote style="color: blue; ">Prader-Willi syndrome: microdeletion on paternal chromosome 15</blockquote></li><li>(2) Complete loss of Prader-Willi gene activity</li><ul> <li>(a) Loss of activated Prader-Willi gene on paternal chromosome 15</li><li>(b) Inactivated Prader-Willi gene on maternal chromosome 15</li> </ul> </ul><li>Microdeletion of the entire gene site on maternal chromosome 15</li><ul> <li>(1) Causes Angelman syndrome</li><li>(2) Complete loss of Angelman gene activity
<blockquote style="color: blue; ">Angelman syndrome: microdeletion on maternal chromosome 15</blockquote></li><ul> <li>(a) Loss of activated Angelman gene on maternal chromosome 15</li><li>(b) Inactivated Angelman gene on paternal chromosome 15</li> </ul> </ul> </ol><li>Clinical findings in Prader-Willi syndrome</li><ol type="a"> <li>Mental retardation, short stature, hypotonia at birth</li><li>Obesity (tendency to overeat), hypogonadism</li> </ol><li>Clinical findings in Angelman syndrome</li><ol type="a"> <li>Mental retardation</li><li>Wide-based gait (resembles a marionette)</li><li>Inappropriate laughter ("happy puppet" syndrome)</li> </ol> </ol>
</div></html>
![[5.IV.A.Multifactorial (polygenic) inheritance]]
<<tiddler [[5.IV.A.Multifactorial (polygenic) inheritance]]>>
![[5.IV.B.Mitochondrial DNA disorders (Fig. 5-18)]]
<<tiddler [[5.IV.B.Mitochondrial DNA disorders (Fig. 5-18)]]>>
![[5.IV.C.Genomic imprinting]]
<<tiddler [[5.IV.C.Genomic imprinting]]>>
<html><a name="HC005040"></a> <br><a name="P005055"></a><div class="PA" style="color: black; "><ol type="1"> <li>Stochastic theory</li><ol type="a"> <li>Cumulative injury to cell membranes and DNA due to free radical injury</li><li>Increased cross-linking of proteins</li><ul> <li>Decreases elasticity</li> </ul><li>Accumulation of errors in protein synthesis adversely affects cellular function.</li> </ol><li>Programmed</li><ul> <li>Apoptosis genes are programmed to kill cells at a set time.</li> </ul> </ol>
</div></html>
![[5.IX.A.Theories]]
<<tiddler [[5.IX.A.Theories]]>>
![[5.IX.B.Age-dependent changes]]
<<tiddler [[5.IX.B.Age-dependent changes]]>>
![[5.IX.C.Age-related changes]]
<<tiddler [[5.IX.C.Age-related changes]]>>
<html><a name="HC005041"></a> <br><a name="P005056"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Age-dependent: inevitable with age; e.g., ↓ GFR, prostate hyperplasia</blockquote>
<ul> <li>Refers to changes that are inevitable with age (<span>[[Table 5-6|Table 5-6. AGE-DEPENDENT CHANGES]]</span>)</li> </ul>
</div></html>
<html><a name="HC005042"></a> <br><a name="P005057"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Age-related: common but <i>not</i> inevitable with age; e.g., Alzheimer's disease, systolic hypertension</blockquote>
<ul> <li>Refers to changes that have a greater incidence with age but are <i>not</i> inevitable (<span>[[Table 5-7|Table 5-7. AGE-RELATED CHANGES]]</span>)</li> </ul>
</div></html>
<html><a name="HC005020"></a> <br><a name="P005036"></a><div class="PA" style="color: black; "><ol type="1"> <li>Absence of the Y chromosome</li><ol type="a"> <li>Germinal tissue differentiates into ovaries.</li><li>Wolffian (mesonephric) duct structures undergo apoptosis.</li> </ol><li>Presence of the Y chromosome
<blockquote style="color: blue; ">Y chromosome: determines the genetic sex of an individual</blockquote></li><ol type="a"> <li>Germinal tissue differentiates into testes.</li><li>Müllerian inhibitory factor (MIF) causes müllerian tissue to undergo apoptosis.</li><ul> <li>MIF is synthesized in the Sertoli cells.</li> </ul><li>Function of fetal testosterone</li><ul> <li>(1) Develops the wolffian duct structures</li><li>(2) Epididymis, seminal vesicles, vas deferens</li> </ul><li>5α-Reductase converts testosterone to dihydrotestosterone (DHT).</li><li>Functions of fetal DHT</li><ul> <li>(1) Develops the prostate gland</li><li>(2) Develops the external male genitalia</li><ul> <li>Genitalia is phenotypically female <i>before</i> DHT is produced.</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC005021"></a> <br><a name="P005037"></a><div class="PA" style="color: black; "><ol type="1"> <li>Fetus has both male and female gonads.</li><li>Karyotype is usually 46,XX.</li> </ol>
</div></html>
<html><a name="HC005022"></a> <br><a name="P005038"></a><div class="PA" style="color: black; "><ol type="1"> <li>Phenotype and genotype do <i>not</i> match.</li><li>Male pseudohermaphrodite</li><ol type="a"> <li>Genotypic male (XY with testes)</li><li>Phenotypic female</li><li>Example-testicular feminization
<blockquote style="color: blue; ">Testicular feminization: most common cause of male pseudohermaphroditism</blockquote></li> </ol><li>Female pseudohermaphrodite</li><ol type="a"> <li>Genotypic female (XX with ovaries)</li><li>Phenotypic male</li><li>Example-virilization in adrenogenital syndrome</li> </ol> </ol>
</div></html>
<html><a name="HC005023"></a><span>[[Fig. 5-20|Figure 5-20]]</span> <br> <br><a name="P005039"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Testicular feminization: defective androgen receptors</blockquote>
<ol type="1"> <li>XR disorder with a defective androgen receptor</li><ul> <li>Fetal DHT and testosterone are unable to function without a receptor.</li> </ul><li>Clinical and laboratory findings</li><ol type="a"> <li>Testicles are present in the inguinal canal or abdominal cavity.</li><li>Müllerian structures are absent because MIF is present.</li><ul> <li>Absence of fallopian tubes, uterus, cervix, upper vagina</li> </ul><li>Male accessory structures are absent.</li><ul> <li><i>No</i> testosterone effect on the wolffian duct structures</li> </ul><li>External genitalia remain female.</li><ul> <li>(1) <i>No</i> DHT effect
<blockquote style="color: blue; ">Testicular feminization: vagina ends as blind pouch</blockquote></li><li>(2) Vagina ends as a blind pouch.</li> </ul><li>Hormone levels</li><ul> <li>(1) Normal male levels of testosterone and DHT</li><li>(2) Slightly increased luteinizing hormone levels</li><li>(3) Slightly increased serum estradiol levels</li><ul> <li>Estrogen activity is unopposed, because estrogen receptors are present.</li> </ul> </ul> </ol><li>Majority of patients are reared female.</li> </ol>
</div></html>
![[5.V.A.Normal sex differentiation]]
<<tiddler [[5.V.A.Normal sex differentiation]]>>
![[5.V.B.True hermaphrodite]]
<<tiddler [[5.V.B.True hermaphrodite]]>>
![[5.V.C.Pseudohermaphrodite]]
<<tiddler [[5.V.C.Pseudohermaphrodite]]>>
![[5.V.D.Testicular feminization (androgen insensitivity syndrome) (Fig. 5-20)]]
<<tiddler [[5.V.D.Testicular feminization (androgen insensitivity syndrome) (Fig. 5-20)]]>>
<html><a name="HC005025"></a> <br><a name="PB005006"></a><div class="BB" style="color: rgb(47, 79, 79); ">Oligohydramnios (decreased amniotic fluid) from decreased production of fetal urine (e.g., renal agenesis, cystic disease of the kidneys) restricts fetal movement in the uterine cavity. As a result, newborns have flat facial features (Potter's facies), underdevelopment of the chest wall, and clubfeet.</div><a name="P005043"></a><div class="PA" style="color: black; "><ol type="1"> <li>Malformations
<blockquote style="color: blue; ">Malformation: disturbance in morphogenesis in embryonic period</blockquote></li><ol type="a"> <li>Disturbances in the morphogenesis (development) of an organ</li><li>Occur between the third and ninth weeks of embryogenesis</li><ul> <li>Most susceptible period is fourth to fifth weeks.</li> </ul><li>Causes</li><ul> <li>Multifactorial (e.g., drugs, infection)
<blockquote style="color: blue; ">Malformation: open neural tube defect, cleft lip/palate</blockquote></li> </ul><li>Examples-open neural tube defects (see <span>[[Figs. 25-6|Figure 25-6]]</span> and <span>[[25-7|Figure 25-7]]</span>), congenital heart disease, cleft lip/palate (see <span>[[Fig. 17-1|Figure 17-1]]</span>)</li> </ol><li>Deformations</li><ol type="a"> <li>Extrinsic disturbances in fetal development
<blockquote style="color: blue; ">Deformation: extrinsic disturbance in fetal development</blockquote></li><li>Occur between the ninth week and term after fetal organs have developed</li><li>Most often due to restricted movement in uterine cavity</li><ul> <li>Examples-oligohydramnios, uterus with leiomyomas, twin pregnancies
<blockquote style="color: blue; ">Deformation: oligohydramnios causing Potter's facies, clubfeet</blockquote></li> </ul> </ol><li>Agenesis</li><ol type="a"> <li>Complete absence of an organ resulting from absence of the anlage (primordial tissue)</li><li>Example-renal agenesis</li> </ol><li>Aplasia</li><ol type="a"> <li>Anlage is present but <i>never</i> develops.</li><li>Example-lung aplasia with tissue containing rudimentary ducts and connective tissue</li> </ol><li>Hypoplasia</li><ol type="a"> <li>Anlage develops incompletely, but the tissue is histologically normal.</li><li>Example-microcephaly</li> </ol><li>Atresia</li><ol type="a"> <li>Incomplete formation of a lumen</li><li>Example-duodenal atresia (see <span>[[Fig. 17-22|Figure 17-22]]</span>)</li> </ol> </ol>
</div></html>
<html><a name="HC005026"></a> <br><a name="P005044"></a><div class="PA" style="color: black; "><ol type="1"> <li>Majority are unknown</li><li>Multifactorial</li><ul> <li>Combination of genetic and environmental factors</li> </ul><li>Environmental factors
<blockquote style="color: blue; ">Congenital anomalies: genetic + environmental factors</blockquote></li><ol type="a"> <li>Maternal disorders</li><ul> <li>(1) Diabetes mellitus</li><ul> <li>(a) Increased risk of neural tube defects and congenital heart disease</li><li>(b) Maternal hyperglycemia causes fetal macrosomia.
<blockquote style="color: blue; ">Maternal diabetes: macrosomia-hyperinsulinemia ↑ muscle mass and fat</blockquote></li><ul> <li>Hyperinsulinemia in the fetus increases muscle mass and stores of fat in the adipose tissue.</li> </ul> </ul><li>(2) Systemic lupus erythematosus</li><ul> <li>Newborn may develop congenital heart block if the mother has anti-Ro antibodies.</li> </ul><li>(3) Hypothyroidism</li><ul> <li>Newborn may develop cretinism.</li> </ul> </ul><li>Drugs and chemicals (<span>[[Table 5-4|Table 5-4. TERATOGENS ASSOCIATED WITH CONGENITAL DEFECTS]]</span>; <span>[[Fig. 5-21|Figure 5-21]]</span>)
<blockquote style="color: blue; ">Alcohol: most common teratogen (fetal alcohol syndrome)</blockquote></li><li>Congenital infections (<span>[[Table 5-5|Table 5-5. CONGENITAL INFECTIONS ASSOCIATED WITH CONGENITAL DEFECTS]]</span>)</li><ul> <li>(1) Newborn has an increase in cord blood IgM.</li><ul> <li>IgM normally is <i>not</i> synthesized in the fetus unless there is a congenital infection.
<blockquote style="color: blue; ">Most common pathogen causing a congenital infection: cytomegalovirus</blockquote></li> </ul><li>(2) Vertical transmission; routes of transmission:</li><ul> <li>(a) Transplacental (most common route)
<blockquote style="color: blue; ">TORCH syndrome = <i>t</i>oxoplasmosis, <i>o</i>ther agents, <i>r</i>ubella, <i>c</i>ytomegalovirus, <i>h</i>erpes simplex virus</blockquote></li><li>(b) Birth canal</li><li>(c) Breast-feeding</li> </ul> </ul><li>Ionizing radiation</li> </ol> </ol>
</div></html>
<html><a name="HC005027"></a> <br><a name="P005045"></a><div class="PA" style="color: black; "><ol type="1"> <li>Timing of teratogenic insult</li><ol type="a"> <li>Malformations occur during the embryonic period (between third and ninth weeks).</li><li>Deformations occur during the fetal period (ninth week to term).</li> </ol><li>Alterations during key steps in morphogenesis
<blockquote style="color: blue; ">Retinoic acid in pregnancy: disrupts <i>HOX</i> gene function (craniofacial, CNS, cardiovascular defects)</blockquote></li><ol type="a"> <li>Mutations may occur in genes normally involved in morphogenesis.</li><ul> <li>Example-mutations of the <i>HOX</i> gene alter development of craniofacial structures.</li> </ul><li>Alterations in cell proliferation, migration, and apoptosis</li> </ol> </ol>
</div><a name="PB005007"></a><div class="BB" style="color: rgb(47, 79, 79); ">Pregnant women should <i>not</i> be treated for acne with retinoic acid. Retinoic acid disrupts the function of the <i>HOX</i> gene, leading to craniofacial, central nervous system, and cardiovascular defects.</div></html>
![[5.VI.A.Types of errors in morphogenesis]]
<<tiddler [[5.VI.A.Types of errors in morphogenesis]]>>
![[5.VI.B.Causes of congenital anomalies]]
<<tiddler [[5.VI.B.Causes of congenital anomalies]]>>
![[5.VI.C.Pathogenesis of congenital anomalies]]
<<tiddler [[5.VI.C.Pathogenesis of congenital anomalies]]>>
<html><a name="HC005029"></a> <br><a name="P005046"></a><div class="PA" style="color: black; "><ol type="1"> <li>Birth of a dead child</li><li>Most often caused by an abruptio placentae
<blockquote style="color: blue; ">Stillbirth: most often caused by abruptio placentae</blockquote></li><ul> <li>Premature separation of the placenta because of a retroplacental blood clot</li> </ul><li>Other causes</li><ul> <li>Maternal diabetes, infection, Rh hemolytic disease of newborn</li> </ul> </ol>
</div></html>
<html><a name="HC005030"></a> <br><a name="P005047"></a><div class="PA" style="color: black; "><ol type="1"> <li>Termination of a pregnancy <i>before</i> 20 weeks</li><li>Most common complication in early pregnancy</li><li>Most often caused by a fetal karyotypic abnormality</li><ul> <li>Usually trisomy 16 in ∼50% of cases
<blockquote style="color: blue; ">Spontaneous abortion: frequently caused by trisomy 16</blockquote></li> </ul><li>Predisposing factors</li><ol type="a"> <li>Advanced maternal age</li><li>Infections (e.g., <i>Streptococcus agalactiae, Listeria monocytogenes</i>)</li><li>Tobacco, alcohol use</li> </ol> </ol>
</div></html>
<html><a name="HC005031"></a> <br><a name="P005048"></a><div class="PA" style="color: black; "><ul> <li>Sudden and unexpected death of an apparently healthy infant from 1 month to 1 year of age</li><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Most common cause of death of an infant younger than 1 year old in developed countries
<blockquote style="color: blue; ">SIDS: majority of deaths occur before age 6 months</blockquote></li><li>Most deaths occur between 2 and 4 months of age.</li><ul> <li>90% occur in infants under 6 months</li> </ul><li>Death usually occurs during sleep.</li> </ol><li>Pathogenesis</li><ol type="a"> <li>No single cause</li><li>Maternal risk factors</li><ul> <li>Examples-smoking, young age</li> </ul><li>Infant risk factors</li><ul> <li>Examples-prematurity, sleeping prone, neural developmental delay, brainstem defect increasing risk for not being able to be aroused from slow wave sleep</li> </ul> </ol><li>Autopsy findings</li><ol type="a"> <li>Nonspecific signs of tissue hypoxia are present.</li><li>Thickened pulmonary arteries</li><li>Petechiae on the pleura and epicardium</li><li>Microscopic changes of hypoxia in the brainstem (e.g., arcuate nucleus)</li> </ol> </ol> </ul>
</div></html>
<html><a name="HC005032"></a> <br><a name="P005049"></a><div class="PA" style="color: black; "><ol type="1"> <li>Newborn classification based on weight and gestational age</li><ol type="a"> <li>Appropriate for gestational age (AGA)</li><li>Small for gestational age (SGA)</li><ul> <li>Highest mortality rate</li> </ul><li>Large for gestational age (LGA)
<blockquote style="color: blue; ">LGA: most often due to maternal diabetes</blockquote></li><ul> <li>Usually due to maternal diabetes mellitus</li> </ul> </ol><li>Prematurity</li><ol type="a"> <li>Gestational age less than 37 weeks</li><ul> <li>Usually weigh less than 2500 g</li> </ul><li>Most common cause of neonatal death and morbidity
<blockquote style="color: blue; ">Prematurity: most common cause neonatal death/morbidity</blockquote></li><li>Risk factors</li><ul> <li>(1) Premature rupture of membranes</li><li>(2) Chorioamnionitis (e.g., <i>Streptococcus agalactiae</i>)</li><li>(3) Placental abnormalities</li><li>(4) Twin pregnancies</li> </ul><li>Complications</li><ul> <li>(1) Respiratory distress syndrome (RDS, decreased surfactant)</li><li>(2) Necrotizing enterocolitis (intestinal ischemia)</li><li>(3) Intraventricular hemorrhage</li> </ul> </ol><li>IUGR usually occurs in SGA infants.
<blockquote style="color: blue; ">IUGR: maternal factors most often responsible in SGA infants</blockquote></li><ul> <li>Defined as <10% of predicted fetal weight for gestational age</li><ol type="a"> <li>Maternal factors</li><ul> <li>(1) Most common cause of IUGR in SGA infants</li><li>(2) Examples-preeclampsia, poor nutrition, drug addiction, alcoholism, smoking</li> </ul><li>Fetal causes</li><ul> <li>(1) Chromosomal disorders, congenital malformations, congenital infections</li><li>(2) Symmetric growth retardation</li><ul> <li>Affects all organ systems equally</li> </ul> </ul><li>Placental causes</li><ul> <li>(1) Abruptio placentae, placental infarction</li><li>(2) Asymmetric growth retardation</li><ul> <li>Example-the brain is spared relative to visceral organs such as the liver.</li> </ul> </ul><li>Ultrasonography is a common initial step in the workup of IUGR.</li><li>About 85% of IUGR infants have oligohydramnios.
<blockquote style="color: blue; ">IUGR: often have oligohydramnios</blockquote></li><ul> <li>(1) Blood flow from peripheral organs (kidneys) is diverted to the brain.</li><li>(2) Renal perfusion and urinary flow rates are reduced in IUGR infants.</li> </ul> </ol> </ul> </ol>
</div></html>
<html><a name="HC005033"></a> <br><a name="P005050"></a><div class="PA" style="color: black; "><ol type="1"> <li>First 4 weeks of life</li><li>Majority of deaths in childhood occur during this period.</li><li>Common causes of death include RDS and congenital anomalies.</li> </ol>
</div></html>
![[5.VII.A.Stillbirth]]
<<tiddler [[5.VII.A.Stillbirth]]>>
![[5.VII.B.Spontaneous abortion (miscarriage)]]
<<tiddler [[5.VII.B.Spontaneous abortion (miscarriage)]]>>
![[5.VII.C.Sudden infant death syndrome (SIDS)]]
<<tiddler [[5.VII.C.Sudden infant death syndrome (SIDS)]]>>
![[5.VII.D.Prematurity and intrauterine growth retardation (IUGR)]]
<<tiddler [[5.VII.D.Prematurity and intrauterine growth retardation (IUGR)]]>>
![[5.VII.E.Neonatal period]]
<<tiddler [[5.VII.E.Neonatal period]]>>
<html><a name="HC005035"></a> <br><a name="P005051"></a><div class="PA" style="color: black; "><ul> <li>Used to identify prenatal genetic defects</li> </ul>
</div></html>
<html><a name="HC005036"></a> <br><a name="P005052"></a><div class="PA" style="color: black; "><ul> <li>Used to rule out neural tube defects</li> </ul>
</div></html>
<html><a name="HC005037"></a> <br><a name="P005053"></a><div class="PA" style="color: black; "><ol type="1"> <li>α-Fetoprotein (AFP)
<blockquote style="color: blue; ">Open neural tube defect: folate deficiency prior to conception; ↑ AFP</blockquote></li><ol type="a"> <li>Increased in neural tube defects</li><li>Causally related to folate deficiency prior to conception</li> </ol><li>Human chorionic gonadotropin (hCG)</li><ul> <li>Levels vary with gestational age.</li> </ul><li>Urine for unconjugated estriol</li><ul> <li>Excellent marker of fetal, placental, or maternal dysfunction</li> </ul><li>Triple marker findings in Down syndrome
<blockquote style="color: blue; ">Triple marker for Down syndrome: ↓ AFP, ↑ hCG, ↓ urine estriol</blockquote></li><ol type="a"> <li>AFP decreased</li><li>hCG increased</li><li>Urine estriol decreased</li> </ol> </ol>
</div></html>
<html><a name="HC005038"></a> <br><a name="P005054"></a><div class="PA" style="color: black; "><ol type="1"> <li>Chromosome karyotyping</li><ul> <li>Identifies numeric and structural abnormalities</li> </ul><li>DNA polymerase chain reaction</li><ul> <li>Amplifies DNA fragments harboring abnormal gene loci</li> </ul><li>Restriction fragment length polymorphism (RFLP)</li><ul> <li>Identifies abnormal gene when the exact site is unknown</li> </ul> </ol>
</div></html>
![[5.VIII.A.Amniocentesis]]
<<tiddler [[5.VIII.A.Amniocentesis]]>>
![[5.VIII.B.Ultrasound]]
<<tiddler [[5.VIII.B.Ultrasound]]>>
![[5.VIII.C.Maternal triple marker screen]]
<<tiddler [[5.VIII.C.Maternal triple marker screen]]>>
![[5.VIII.D.Genetic analysis]]
<<tiddler [[5.VIII.D.Genetic analysis]]>>
<html><a name="HC006002"></a> <br><a name="P006002"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Smoking: most important preventable cause of disease and death in United States</blockquote>
<ol type="1"> <li>Tobacco is the leading cause of premature death in the United States.</li><li>The rate of cigarette smoking is increasing in females and decreasing in males.</li><li>Chemical components of tobacco</li><ol type="a"> <li>Nicotine</li><ul> <li>(1) Rapidly absorbed</li><li>(2) Most addictive chemical in tobacco smoke</li><li>(3) Cotinine is the most important metabolite of nicotine.
<blockquote style="color: blue; ">Cotinine: metabolite of nicotine; used for screening</blockquote></li><ul> <li>Screening test in blood or urine for detecting nicotine</li> </ul> </ul><li>Polycyclic hydrocarbons are the primary carcinogens.</li> </ol><li>Smokeless tobacco (e.g., chewing tobacco)</li><ol type="a"> <li>Can cause nicotine addiction and cancer</li><li>Risk for squamous cell cancer of buccal mucosa and gums</li> </ol><li>Passive (secondhand) smoke inhalation</li><ol type="a"> <li>Greatest impact on children</li><ul> <li>(1) Increased risk of respiratory and middle ear infections</li><li>(2) Exacerbates asthma</li> </ul><li>Increased risk for lung cancer and coronary artery disease</li> </ol><li>Systemic effects associated with tobacco use (<span>[[Table 6-1|Table 6-1. SYSTEMIC EFFECTS ASSOCIATED WITH TOBACCO USE]]</span>)</li><li>Beneficial effects of smoking cessation</li><ol type="a"> <li>Live longer, regardless of age, than those who continue to smoke</li><ul> <li>If cessation <i>before</i> age 50, reduction in risk of dying in next 15 years is cut in half compared with those who continue to smoke.</li> </ul><li>Lower risk for cardiovascular disease</li><ul> <li>Approaches nonsmoker after 15 years
<blockquote style="color: blue; ">Nicotine patch: effective in treating ulcerative colitis</blockquote></li> </ul><li>Lower risk for lung cancer</li><ul> <li>Approaches nonsmoker after 15 years</li> </ul><li>Lower risk for stroke</li><ul> <li>Approaches nonsmoker after 5 to 15 years</li> </ul><li>Other benefits</li><ul> <li>(1) Reduced risk for cancers of the mouth, larynx, esophagus, pancreas, kidney, and urinary bladder</li><li>(2) Improved pulmonary function regardless of severity of the disease</li><li>(3) Reduced risk for pneumonia, influenza, and bronchitis</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC006003"></a> <br><a name="P006003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Alcohol metabolism</li><ol type="a"> <li>Absorption occurs in the stomach (25%)</li><li>Metabolism occurs in the stomach and liver</li><ul> <li>Alcohol dehydrogenase is the rate-limiting enzyme.
<blockquote style="color: blue; ">Alcohol metabolism: ↑ NADH is key to lab abnormalities</blockquote></li> </ul><li>Important products of alcohol metabolism (<span>[[Fig. 6-1|Figure 6-1]]</span>)</li><ul> <li>(1) Reduced nicotinamide adenine dinucleotide (NADH)</li><ul> <li>(a) Causes conversion of pyruvate to lactate</li><li>(b) Causes conversion of acetoacetate to β-hydroxybutyrate</li><li>(c) Causes conversion of dihydroxyacetone phosphate to glycerol 3-phosphate</li> </ul><li>(2) Acetyl coenzyme A (acetyl CoA)</li><ul> <li>(a) Used to synthesize fatty acids for triglyceride synthesis</li><li>(b) Used to synthesize ketoacids</li> </ul> </ul><li>Alcohol induction of the cytochrome P-450 enzyme system</li><ul> <li>Increases alcohol metabolism, which increases the tolerance for alcohol</li> </ul><li>Legal blood alcohol limit for driving</li><ul> <li>Ranges from 80 to 100 mg/dL</li> </ul> </ol><li>Risk factors for alcohol-related disease</li><ol type="a"> <li>Amount</li><li>Duration</li><li>Female sex
<blockquote style="color: blue; ">Women: less gastric alcohol dehydrogenase than men</blockquote></li><ul> <li>(1) Decreased gastric alcohol dehydrogenase levels</li><ul> <li>Causes higher alcohol levels in women than in men, even after drinking the same amount of alcohol</li> </ul><li>(2) Genetic susceptibility</li> </ul> </ol><li>Systemic effects associated with alcohol abuse (<span>[[Table 6-2|Table 6-2. SYSTEMIC EFFECTS ASSOCIATED WITH ALCOHOL ABUSE]]</span>)
<blockquote style="color: blue; ">Alcohol abuse: most common cause of thiamine deficiency</blockquote></li><li>Laboratory findings in alcohol abuse</li><ol type="a"> <li>Fasting hypoglycemia</li><ul> <li>Excess NADH causes pyruvate (substrate for gluconeogenesis) to convert to lactate.</li> </ul><li>Increased anion gap metabolic acidosis</li><ul> <li>(1) Lactic acidosis</li><li>(2) β-Hydroxybutyric ketoacidosis</li><ul> <li>(a) Excess acetyl CoA is converted to β-hydroxybutyrate.</li><li>(b) <i>Not</i> detected with urine dipstick or blood test for ketone bodies
<blockquote style="color: blue; ">↑ Anion gap metabolic acidosis in alcohol abuse: lactic acid, β-hydroxybutyric acid</blockquote></li> </ul> </ul><li>Other findings</li><ul> <li>(1) Hyperuricemia (potential for developing gout)</li><ul> <li>Lactic acid and β-hydroxybutyric acid compete with uric acid for excretion in the proximal tubules.</li> </ul><li>(2) Hypertriglyceridemia</li><ul> <li>Increased production of glycerol 3-phosphate, the key substrate for triglyceride synthesis in the liver</li> </ul><li>(3) Serum aspartate aminotransferase (AST) greater than serum alanine aminotransferase (ALT) in liver disease (90% sensitivity, 75% specificity)</li><ul> <li>Alcohol is a mitochondrial toxin that causes release of AST, which is located in the mitochondria.
<blockquote style="color: blue; ">Alcohol liver disease: AST > ALT; ↑ GGT</blockquote></li> </ul><li>(4) Increased serum γ-glutamyltransferase (GGT; 75% sensitivity, 90% specificity)</li><ul> <li>Alcohol induces hyperplasia of the smooth endoplasmic reticulum causing increased synthesis of GGT.</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC006004"></a> <br><a name="P006004"></a><div class="PA" style="color: black; "><ul> <li>Sedatives, stimulants, hallucinogens (<span>[[Table 6-3|Table 6-3. SELECTED DRUGS OF ABUSE AND THEIR EFFECTS]]</span>)</li><ol type="1"> <li>CNS effects of long-term drug abuse</li><ol type="a"> <li>Damage to neurotransmitter receptor sites</li><li>Cerebral atrophy (e.g., alcohol)</li> </ol><li>Complications of intravenous drug use (IVDU)</li><ol type="a"> <li>Hepatitis B
<blockquote style="color: blue; ">Hepatitis B: most common systemic complication of IVDU</blockquote></li><li>HIV</li><li>Infective endocarditis (tricuspid/aortic valves)</li><ul> <li>Caused by <i>Staphylococcus aureus</i></li> </ul><li>Tetanus</li><ul> <li>Complication of "skin popping" using a dirty needle</li> </ul> </ol> </ol> </ul>
</div></html>
![[6.I.A.Tobacco use]]
<<tiddler [[6.I.A.Tobacco use]]>>
![[6.I.B.Alcohol abuse]]
<<tiddler [[6.I.B.Alcohol abuse]]>>
![[6.I.C.Other drugs of abuse]]
<<tiddler [[6.I.C.Other drugs of abuse]]>>
![[6.I.D.Adverse effects of therapeutic drug use (Table 6-4)]]
<<tiddler [[6.I.D.Adverse effects of therapeutic drug use (Table 6-4)]]>>
![[6.I.E.Injuries caused by environmental chemicals (Table 6-5)]]
<<tiddler [[6.I.E.Injuries caused by environmental chemicals (Table 6-5)]]>>
![[6.I.F.Injuries caused by arthropods and reptiles (Table 6-6 and Fig. 6-2)]]
<<tiddler [[6.I.F.Injuries caused by arthropods and reptiles (Table 6-6 and Fig. 6-2)]]>>
<html><a name="HC006005"></a><span>[[Table 6-4|Table 6-4. ADVERSE REACTIONS ASSOCIATED WITH THERAPEUTIC DRUG USE]]</span> <br> <br><a name="P006005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Acetaminophen</li><ol type="a"> <li>Conversion to free radicals in the liver</li><li>May result in damage to the liver (e.g., fulminant hepatitis)</li><li>May result in damage to the kidneys (e.g., renal papillary necrosis)</li> </ol><li>Aspirin (acetylsalicylic acid) overdose</li><ol type="a"> <li>General symptoms</li><ul> <li>Tinnitus, vertigo, change in mental status (confusion, seizures), tachypnea</li> </ul><li>Acid-base disorders</li><ul> <li>(1) Respiratory alkalosis may occur initially (within 12-24 hours).</li><ul> <li>(a) Due to direct stimulation of the respiratory center</li><li>(b) Respiratory acidosis may occur as a late finding.</li> </ul><li>(2) Shift to metabolic acidosis with an increased anion gap</li><ul> <li>Occurs more often in children</li> </ul><li>(3) Mixed primary respiratory alkalosis and metabolic acidosis</li><ul> <li>Occurs more often in adults
<blockquote style="color: blue; ">Salicylate poisoning: danger of hyperthermia</blockquote></li> </ul> </ul><li>Hyperthermia</li><ul> <li>(1) Salicylates damage the inner mitochondrial membrane.</li><li>(2) Oxidative energy is released as heat, <i>not</i> as adenosine triphosphate.</li> </ul><li>Hemorrhagic gastritis, fulminant hepatitis
<blockquote style="color: blue; ">Both acetaminophen and aspirin cause fulminant hepatitis.</blockquote></li> </ol><li>Disorders associated with exogenous estrogen <i>without</i> progestin</li><ol type="a"> <li>Cancer (adenocarcinoma)</li><ul> <li>Endometrium, breast</li> </ul><li>Venous thromboembolism</li><ul> <li>(1) Estrogen decreases synthesis of antithrombin III (ATIII).</li><ul> <li>ATIII normally neutralizes activated coagulation factors.
<blockquote style="color: blue; ">Unopposed estrogen: thrombogenic, carcinogenic, cholestasis</blockquote></li> </ul><li>(2) Estrogen increases synthesis of factors I (fibrinogen), V, and VIII.</li> </ul><li>Intrahepatic cholestasis with jaundice</li><li>Cardiovascular effects</li><ul> <li>Myocardial infarction (MI), stroke</li> </ul> </ol><li>Disorders associated with oral contraceptives</li><ul> <li>Contain estrogen and progestin</li><ol type="a"> <li>Cancer</li><ul> <li>(1) Breast (adenocarcinoma)</li><li>(2) Cervix (squamous cell carcinoma)</li> </ul><li>Venous thromboembolism
<blockquote style="color: blue; ">Oral contraceptives: ↓ risk for endometrial and ovarian cancer (only surface type)</blockquote></li><ul> <li>Similar pathogenesis to estrogen without progestin</li> </ul><li>Folate deficiency</li><ul> <li>Decreases jejunal reabsorption of folate</li> </ul><li>Hypertension</li><ul> <li>Due to increased synthesis of angiotensinogen
<blockquote style="color: blue; ">Oral contraceptives: most common cause of hypertension in young women</blockquote></li> </ul><li>Hepatic adenoma</li><ul> <li>Risk of intraperitoneal hemorrhage</li> </ul><li>Intrahepatic cholestasis with jaundice</li><li>Cholesterol gallstones</li><ul> <li>Estrogen increases cholesterol excretion in bile.</li> </ul> </ol> </ul> </ol>
</div></html>
<html><a name="HC006006"></a><span>[[Table 6-5|Table 6-5. ENVIRONMENTAL CHEMICALS AND ASSOCIATED TOXIC EFFECTS]]</span> <br> <br> </html>
<html><a name="HC006007"></a><span>[[Fig. 6-2|Figure 6-2]]</span> <br><span>[[Table 6-6|Table 6-6. INJURIES CAUSED BY ARTHROPODS AND REPTILES]]</span> <br> <br><a name="P006006"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Bee/wasp/hornet sting: most common cause of death due to a venomous bite</blockquote>
</div></html>
<html><a name="HC006009"></a> <br><a name="P006008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Types of skin wounds</li><ol type="a"> <li>Contusion (bruise)</li><ul> <li>Blunt force injury to blood vessels with subsequent escape of blood into tissue</li> </ul><li>Abrasion</li><ul> <li>Superficial excoriation of the epidermis</li> </ul><li>Laceration</li><ul> <li>Jagged tear with intact bridging blood vessels, nerves, and connective tissue</li> </ul> </ol><li>Incision</li><ul> <li>Wound with sharp margins with severed bridging blood vessels</li><ol type="a"> <li>Gunshot wounds</li><ul> <li>(1) Contact wounds</li><li>(2) Stellate-shaped</li> </ul><li>Contain soot and gunpowder (fouling)
<blockquote style="color: blue; ">Contact gunshot wound: fouling</blockquote></li><li>Intermediate-range wounds</li><ul> <li>Powder tattooing (stippling) of the skin around the entrance site
<blockquote style="color: blue; ">Intermediate range wound powder tattooing</blockquote></li> </ul><li>Long-range wounds</li><ul> <li><i>No</i> powder tattooing</li> </ul><li>Exit wounds</li><ul> <li>Typically larger and more irregular than entrance wounds</li> </ul> </ol> </ul><li>Motor vehicle collisions
<blockquote style="color: blue; ">Motor vehicle collisions: most common cause of accidental death in people ages 1 to 39 years</blockquote></li><ol type="a"> <li>Frequently cause mechanical injury</li><li>Frequently alcohol-related</li> </ol><li>Shaken baby syndrome</li><ol type="a"> <li>More than 50% of deaths in child abuse are due to this syndrome.</li><li>Majority are <1 year old</li><li>Characteristic signs</li><ul> <li>(1) Retinal hemorrhages</li><li>(2) Multiple fractures of long bones
<blockquote style="color: blue; ">Shaken baby syndrome: retinal hemorrhages</blockquote></li><li>(3) Subdural hematomas</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC006010"></a> <br><a name="P006009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Burns</li><ol type="a"> <li>First-degree</li><ul> <li>(1) Painful partial-thickness burns (e.g., sunburn)</li><li>(2) Heal without scarring</li> </ul><li>Second-degree</li><ul> <li>(1) Painful partial-thickness burns</li><li>(2) Damage to entire epidermis</li><li>(3) Blister formation</li><li>(4) Usually heal without scarring
<blockquote style="color: blue; ">First- and second-degree burns: no permanent scarring</blockquote></li> </ul><li>Third-degree</li><ul> <li>(1) Painless full-thickness burns</li><li>(2) Extensive necrosis of epidermis and adnexa</li><li>(3) Scarring is inevitable.</li><ul> <li>(a) Keloids (exaggerated scars) commonly occur.</li><li>(b) Potential for developing squamous cell carcinoma</li> </ul><li>(4) Healing of epithelial surface</li><ul> <li>Proliferation of residual epithelium located at burn margins and lining adnexal structures</li> </ul> </ul><li>Complications</li><ul> <li>(1) Infection</li><ul> <li>Sepsis due to <i>Pseudomonas aeruginosa</i> is the most common cause of death in burn patients.
<blockquote style="color: blue; ">Most common cause of death in burn patients: sepsis caused by <i>Pseudomonas aeruginosa</i></blockquote></li> </ul><li>(2) Curling's ulcers (stomach)</li> </ul> </ol><li>Minor heat syndromes</li><ol type="a"> <li>Heat edema</li><ul> <li>(1) Mild swelling of feet, ankles, and hands</li><li>(2) Cutaneous vasodilation with pooling of blood in gravity-dependent extremities</li><li>(3) Occurs in the elderly nonacclimatized individuals; healthy travelers coming from cold to hot environment</li><li>(4) Self-limited</li> </ul><li>Heat cramps (<span>[[Table 6-7|Table 6-7. HEAT INJURIES*]]</span>)</li><ul> <li>(1) Painful, involuntary spasmodic contractions of muscle</li><ul> <li>(a) Usually starts in calves but may progress to other muscle groups</li><li>(b) Due to deficiency of sodium, potassium, and fluids in muscle fibers</li> </ul><li>(2) May occur in individuals sweating profusely without proper fluid replacement</li><li>(3) Treatment</li><ul> <li>Commercially available electrolyte solution drinks</li> </ul> </ul><li>Heat exhaustion (see <span>[[Table 6-7|Table 6-7. HEAT INJURIES*]]</span>)</li><ul> <li>(1) Significant volume depletion (salt and water depletion) with or without increase in body temperature</li><ul> <li>(a) Orthostatic hypotension, dizziness, headache, nausea/vomiting</li><li>(b) Core temperature variable; normal to 40°C (104°F)</li><li>(c) No anhidrosis (absence of sweating); normal mental status examination
<blockquote style="color: blue; ">Heat exhaustion: ≤ 40°C (<104°F); no anhidrosis/no mental status changes</blockquote></li> </ul><li>(2) Laboratory studies</li><ul> <li>(a) Hemoconcentration (e.g., ↑ hemoglobin/hematocrit)</li><li>(b) Variable serum Na<sup>+</sup> depending on previous intake</li><ul> <li>Hypernatremia (no intake), normal, or hyponatremia (patient drank water without electrolytes)</li> </ul> </ul><li>(3) Treatment</li><ul> <li>(a) Intravenous volume and electrolyte replacement</li><li>(b) May progress to heat stroke if not treated promptly</li> </ul> </ul> </ol><li>Major heat syndrome: heat stroke (see <span>[[Table 6-7|Table 6-7. HEAT INJURIES*]]</span>)</li><ol type="a"> <li>Similar presentation as heat exhaustion, except the following</li><ul> <li>(1) Core body temperature > 40°C (104°F)</li><li>(2) Anhidrosis; mental status (e.g., do not know time, date) and CNS dysfunction (e.g., ataxia, cerebral edema, seizures)</li> </ul><li>Treatment</li><ul> <li>(1) High-flow O<sub>2</sub>; intravenous fluids (normal saline, Ringer's lactate)</li><li>(2) Rapid cooling to < 40°C (104°F)
<blockquote style="color: blue; ">Heat stroke: > 40° C (>104° F), anhidrosis (absence of sweating), impaired consciousness</blockquote></li> </ul> </ol><li>Frostbite</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Localized tissue injury caused by direct damage (e.g., ice crystallization in cells)</li><li>(2) Indirect damage (e.g., vasodilation, thrombosis)</li> </ul><li>Clinical findings</li><ul> <li>(1) Loss of pain sensation or burning/tingling sensation</li><li>(2) Discoloration of the skin; waxy appearance; cold to the touch</li><li>(3) Left untreated, skin gradually darkens (becomes completely black) and blisters</li> </ul><li>Treatment principles</li><ul> <li>(1) Pre-thaw: stabilize core body temperature; rehydration</li><li>(2) Thaw: immerse in circulating water 37°C to 40°C; ibuprofen</li><li>(3) Post-thaw: dry and elevate body part</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC006011"></a> <br><a name="P006010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Produced by alternating current (AC) and direct current (DC)</li><ol type="a"> <li>AC is more dangerous than DC.
<blockquote style="color: blue; ">AC more dangerous than DC</blockquote></li><li>AC produces tetanic contractions.</li><li>DC produces a single shock.</li><li>Wet skin decreases resistance, which increases current.</li><li>Dry skin increases resistance, which decreases current.</li><li>Tissue damage increases with increased voltage and duration of exposure.</li><li>Current moving from the left arm to the right leg</li><ul> <li>(1) Most dangerous route, because it affects the heart</li><li>(2) Death results from cardiorespiratory arrest.</li> </ul> </ol><li>Lightning injury</li><ol type="a"> <li>100 to 200 deaths/year</li><li>Hair on end; buzzing</li><li>Mortality rate 30% with direct strike</li> </ol> </ol>
</div></html>
<html><a name="HC006012"></a> <br><a name="P006011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Common cause of death in children from 1 to 14 years of age</li><li>Terminology</li><ol type="a"> <li>Drowning refers to death by suffocation from immersion in liquid.</li><li>Near drowning is defined as survival following asphyxia secondary to submersion.</li><li>Diving reflex occurs in water that is colder than 20°C (70°F).</li><ul> <li>(1) Bradycardia</li><li>(2) Peripheral vasoconstriction</li><ul> <li>Shunts blood to more vital areas.</li> </ul><li>(3) Blood shifting</li><ul> <li>Shift to thoracic cavity to prevent lung collapse</li> </ul><li>(4) Allows both conscious and unconscious person to survive longer without O<sub>2</sub></li> </ul><li>Wet drowning
<blockquote style="color: blue; ">Most common drowning: wet drowning</blockquote></li><ul> <li>(1) ∼90% of cases</li><li>(2) Initial laryngospasm on contact with water followed by relaxation and aspiration of water</li> </ul><li>Dry drowning is characterized by intense laryngospasm <i>without</i> aspiration.</li> </ol><li>Pathophysiology</li><ol type="a"> <li>Lung aspiration of fresh water (90% of cases)</li><ul> <li>(1) Due to its hypotonicity, water is reabsorbed from the alveoli into the pulmonary circulation.</li><li>(2) Plasma is diluted causing hemolysis of RBCs (hemoglobinuria), hyponatremia, hyperkalemia.</li><li>(3) Electrolyte abnormalities precipitate ventricular fibrillation.</li><ul> <li>Most common cause of death</li> </ul><li>(4) Hemoglobinuria can produce acute renal failure.</li> </ul><li>Lung aspiration of salt water (10% of cases)</li><ul> <li>(1) Salt water is more isotonic to blood (no RBC hemolysis).</li><li>(2) Cause of death is asphyxia from pulmonary edema.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC006013"></a> <br><a name="P006012"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">High altitude: O<sub>2</sub> concentration 21%, ↓ atmospheric pressure</blockquote>
<ol type="1"> <li>General</li><ol type="a"> <li>O<sub>2</sub> concentration 21%</li><li>Decreased barometric pressure</li><li>Hypoxemic stimulus to chemoreceptors increases the respiratory rate producing respiratory alkalosis.</li><ul> <li>Decrease in Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> causes a corresponding increase in Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>.</li> </ul><li>Respiratory alkalosis activates glycolysis.</li><ul> <li>(1) Increased synthesis of 2,3-bisphosphoglycerate
<blockquote style="color: blue; ">High altitude: respiratory alkalosis; right-shifted OBC</blockquote></li><li>(2) Right-shifts O<sub>2</sub>-binding curve (OBC)</li><ul> <li>Increases release of O<sub>2</sub> to tissue</li> </ul> </ul> </ol><li>Acute mountain sickness</li><ol type="a"> <li>Usually occurs at above 8000 feet (2440 m) elevation</li><li>Risk factors</li><ul> <li>(1) Increased rate of ascent</li><li>(2) Extreme altitude</li> </ul><li>Clinical findings</li><ul> <li>(1) Headache (most common)</li><li>(2) Fatigue, dizziness, anorexia, insomnia</li><li>(3) Acute pulmonary edema</li><ul> <li>Noncardiogenic (exudate)</li> </ul><li>(4) Acute cerebral edema</li><ul> <li>Ataxia, stupor, coma</li> </ul> </ul><li>Treatment</li><ul> <li>Immediate descent (if severe complications)</li> </ul> </ol> </ol>
</div></html>
![[6.II.A.Mechanical injury]]
<<tiddler [[6.II.A.Mechanical injury]]>>
![[6.II.B.Thermal injury]]
<<tiddler [[6.II.B.Thermal injury]]>>
![[6.II.C.Electrical injury]]
<<tiddler [[6.II.C.Electrical injury]]>>
![[6.II.D.Drowning]]
<<tiddler [[6.II.D.Drowning]]>>
![[6.II.E.High altitude injury]]
<<tiddler [[6.II.E.High altitude injury]]>>
<html><a name="HC006015"></a> <br><a name="P006014"></a><div class="PA" style="color: black; "><ul> <li>Examples-x-rays, γ-rays</li><ol type="1"> <li>Pathophysiology</li><ol type="a"> <li>Injury correlates with type of radiation, cumulative dose, and amount of surface area exposed.
<blockquote style="color: blue; ">Ionizing radiation: damage to DNA</blockquote></li><li>Direct or indirect DNA injury occurs via formation of hydroxyl free radicals.</li> </ol><li>Tissue susceptibility</li><ol type="a"> <li>Most radiosensitive tissues (highest mitotic activity)</li><ul> <li>(1) Lymphoid tissue (most sensitive)
<blockquote style="color: blue; ">Lymphoid tissue: most sensitive to radiation</blockquote></li><li>(2) Bone marrow</li><li>(3) Mucosa of gastrointestinal tract, germinal tissue</li> </ul><li>Least radiosensitive tissues</li><ul> <li>(1) Bone (least sensitive)
<blockquote style="color: blue; ">Bone: least sensitive tissue to radiation</blockquote></li><li>(2) Brain, muscle, skin</li> </ul> </ol><li>Radiation effects in different tissues</li><ol type="a"> <li>Hematopoietic</li><ul> <li>(1) Lymphopenia (first change)</li><li>(2) Thrombocytopenia
<blockquote style="color: blue; ">Total body radiation: lymphopenia first hematologic sign</blockquote></li><li>(3) Bone marrow hypoplasia</li> </ul><li>Vascular</li><ul> <li>(1) Thrombosis (early), fibrosis (late)</li><li>(2) Ischemic damage</li> </ul><li>Epidermal</li><ul> <li>(1) Acute effects are erythema, edema, blistering.</li><li>(2) Chronic effect is radiodermatitis.</li><ul> <li>Potential for squamous cell carcinoma</li> </ul> </ul><li>Gastrointestinal</li><ul> <li>(1) Acute effect is diarrhea.</li><li>(2) Chronic effects are adhesions with potential for bowel obstruction.</li> </ul> </ol><li>Cancers caused by radiation</li><ol type="a"> <li>Acute leukemia (most common)
<blockquote style="color: blue; ">Acute leukemia: most frequent type of cancer caused by radiation</blockquote></li><li>Papillary carcinoma of the thyroid</li><li>Osteogenic sarcoma</li> </ol> </ol> </ul>
</div></html>
<html><a name="HC006016"></a> <br><a name="P006015"></a><div class="PA" style="color: black; "><ol type="1"> <li>Ultraviolet light B (UVB) is most damaging</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Pyrimidine dimers distort the DNA helix (see <span>[[Fig. 8-4|Figure 8-4]]</span>).
<blockquote style="color: blue; ">UVB: increase in pyrimidine dimers distorts DNA helix</blockquote></li><li>(2) Inactivation of the <i>TP53</i> suppressor gene</li><li>(3) Activation of the <i>RAS</i> oncogene</li> </ul><li>General effects</li><ul> <li>(1) Sunburn</li><li>(2) Actinic (solar) keratosis (see <span>[[Fig. 24-7A|Figure 24-7]]</span>)</li><ul> <li>Precursor of squamous cell carcinoma (2-5% of cases)</li> </ul><li>(3) Corneal burns from skiing</li> </ul><li>Cancers</li><ul> <li>(1) Basal cell carcinoma (most common) (see <span>[[Fig. 24-7B|Figure 24-7]]</span>)
<blockquote style="color: blue; ">Basal cell carcinoma: most common UVB light-related skin cancer</blockquote></li><li>(2) Squamous cell carcinoma (see <span>[[Fig. 24-7D|Figure 24-7]]</span>), malignant melanoma (see <span>[[Fig. 24-5H|Figure 24-5]]</span>)</li> </ul> </ol><li>Effects of other types of radiation</li><ol type="a"> <li>Laser radiation</li><ul> <li>Third-degree burns</li> </ul><li>Microwave radiation</li><ul> <li>Skin burns, cataracts, sterility</li> </ul><li>Infrared radiation</li><ul> <li>Skin burns, cataracts</li> </ul> </ol> </ol>
</div></html>
![[6.III.A.Ionizing radiation injury]]
<<tiddler [[6.III.A.Ionizing radiation injury]]>>
![[6.III.B.Nonionizing radiation]]
<<tiddler [[6.III.B.Nonionizing radiation]]>>
<html><a name="HC007002"></a> <br><a name="P007001"></a><div class="PA" style="color: black; "><ol type="1"> <li>Optimal dietary intake of nutrients that under ordinary conditions will keep the general population in good health</li><li>Varies with sex, age, body weight, diet, and physiologic status</li> </ol>
</div></html>
<html><a name="HC007003"></a> <br><a name="P007002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Factors influencing DEE</li><ol type="a"> <li>Basal metabolic rate (BMR)</li><li>Thermic effect of food</li><li>Physical activity</li> </ol><li>BMR
<blockquote style="color: blue; ">BMR: most important factor in determining daily energy expenditure</blockquote></li><ol type="a"> <li>Accounts for ∼60% of DEE</li><li>Energy consumption involved in normal body functions</li><ul> <li>Examples-cardiac function, maintaining ion pumps</li> </ul><li>Body weight is the most important factor determining BMR.</li><li>Thyroid function alters the BMR.</li><ul> <li>BMR is increased or decreased in hyperthyroidism and hypothyroidism, respectively.
<blockquote style="color: blue; ">BMR: ↓ hypothyroidism, ↑ hyperthyroidisim</blockquote></li> </ul> </ol><li>Thermic effect of foods</li><ul> <li>Energy used in digestion, absorption, and distribution of nutrients</li> </ul><li>Degree of physical activity</li> </ol>
</div></html>
![[7.I.A.Recommended dietary allowance (RDA)]]
<<tiddler [[7.I.A.Recommended dietary allowance (RDA)]]>>
![[7.I.B.Daily energy expenditure (DEE)]]
<<tiddler [[7.I.B.Daily energy expenditure (DEE)]]>>
<html><a name="HC007005"></a> <br><a name="P007003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Glucose</li><ol type="a"> <li>Stored primarily as glycogen in liver and muscle</li><li>RBCs use only glucose for energy.</li><li>Complete oxidation produces 4 kcal/g.</li> </ol><li>Enzymatic digestion
<blockquote style="color: blue; ">Carbohydrate digestion: begins in the mouth; 4 kcal/g</blockquote></li><ol type="a"> <li>Begins in the mouth (amylase)</li><li>Pancreatic amylase</li><ul> <li>In chronic pancreatitis, carbohydrates are <i>not</i> malabsorbed due to predigestion by salivary amylase.</li> </ul><li>Brush border intestinal enzymes (disaccharidases)</li><ul> <li>(1) Hydrolyze lactose (galactose + glucose), maltose (glucose + glucose), and sucrose (fructose + glucose)
<blockquote style="color: blue; ">Disaccharidases: produce glucose, galactose, fructose</blockquote></li><li>(2) Disaccharidases produce glucose, galactose, and fructose.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC007006"></a> <br><a name="P007004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Amino acids are substrates for gluconeogenesis.
<blockquote style="color: blue; ">Amino acids: substrates for gluconeogenesis</blockquote></li><ol type="a"> <li>Transaminases remove amine groups to form corresponding α-ketoacid.</li><li>Examples-alanine becomes pyruvate, aspartate becomes oxaloacetic acid</li> </ol><li>Digestion</li><ol type="a"> <li>Begins in the stomach (pepsin and acid)
<blockquote style="color: blue; ">Protein digestion: begins in the stomach; pepsin and acid</blockquote></li><li>Pancreatic proteases (e.g., trypsin) and peptidases release amino acids.</li> </ol><li>Complete oxidation produces 4 kcal/g.</li> </ol>
</div></html>
<html><a name="HC007007"></a> <br><a name="P007005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Triglycerides</li><ol type="a"> <li>Major dietary lipids</li><li>Major source of energy for cells <i>except</i> RBCs and brain</li> </ol><li>Essential fatty acids (FAs)
<blockquote style="color: blue; ">Essential FAs: linolenic, linoleic acids</blockquote></li><ol type="a"> <li>Linolenic acid (ω-3) is cardioprotective.</li><li>Linoleic acid (ω-6) is required for synthesis of arachidonic acid.</li><li>Deficiency of essential fatty acids</li><ul> <li>(1) Scaly dermatitis, hair loss</li><li>(2) Poor wound healing</li> </ul> </ol><li>Digestion of dietary triglyceride (TG)</li><ol type="a"> <li>Occurs primarily in the small intestine
<blockquote style="color: blue; ">Fat digestion: begins in the small intestine</blockquote></li><ul> <li>(1) Hydrolyzed by pancreatic lipase</li><ul> <li>Produces monoglycerides (MGs) and FAs</li> </ul><li>(2) Bile salts/acid produce micelles to enhance reabsorption by villi.
<blockquote style="color: blue; ">Fat digestion: pancreas → bile salts/acids → intestinal cells</blockquote></li><ul> <li>Contain MGs, FAs, fat-soluble vitamins, and cholesterol esters</li> </ul><li>(3) Intestinal cells resynthesize TG and package it into chylomicrons, which enter the blood.</li><ul> <li>Formation and secretion of chylomicrons requires apolipoprotein B48.</li> </ul> </ul><li>Complete oxidation produces 9 kcal/g.</li> </ol> </ol>
</div></html>
![[7.II.A.Carbohydrates]]
<<tiddler [[7.II.A.Carbohydrates]]>>
![[7.II.B.Proteins]]
<<tiddler [[7.II.B.Proteins]]>>
![[7.II.C.Fats]]
<<tiddler [[7.II.C.Fats]]>>
<html><a name="HC007009"></a> <br><a name="P007006"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Inadequate protein intake
<blockquote style="color: blue; ">Kwashiorkor: inadequate protein intake</blockquote></li><li>Adequate caloric intake consisting mainly of carbohydrates</li><li>Protein in liver and other organs (i.e., visceral protein) is decreased.</li><li>Muscle protein (i.e., somatic protein) is relatively unchanged.</li> </ol><li>Clinical findings (<span>[[Fig. 7-1|Figure 7-1]]</span>, left)</li><ol type="a"> <li>Pitting edema and ascites
<blockquote style="color: blue; ">Pitting edema is characteristic of kwashiorkor</blockquote></li><ul> <li>Caused by hypoalbuminemia and loss of plasma oncotic pressure</li> </ul><li>Fatty liver
<blockquote style="color: blue; ">Kwashiorkor: fatty liver; ↓ apoB synthesis</blockquote></li><ul> <li>(1) Caused by decreased synthesis of apolipoproteins</li><li>(2) Apolipoprotein B-100 is required for assembly and secretion of very low density lipoproteins (VLDLs) in the liver.</li> </ul><li>Diarrhea</li><ul> <li>Caused by loss of the brush border enzymes and parasitic infections</li> </ul><li>Anemia and defects in cell-mediated immunity (CMI)</li> </ol> </ol>
</div></html>
<html><a name="HC007010"></a> <br><a name="P007007"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Marasmus: total calorie deprivation</blockquote>
<ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Dietary deficiency of both protein and calories</li><li>Decrease in somatic protein (muscle protein)</li> </ol><li>Clinical findings (see <span>[[Fig. 7-1|Figure 7-1]]</span>, right)</li><ol type="a"> <li>Extreme muscle wasting ("broomstick extremities")
<blockquote style="color: blue; ">Extreme muscle wasting is common in marasmus.</blockquote></li><ul> <li>(1) Breakdown of muscle protein for energy</li><li>(2) Loss of subcutaneous fat</li> </ul><li>Growth retardation; anemia; defects in CMI</li> </ol> </ol>
</div></html>
![[7.III.A.Kwashiorkor]]
<<tiddler [[7.III.A.Kwashiorkor]]>>
![[7.III.B.Marasmus]]
<<tiddler [[7.III.B.Marasmus]]>>
<html><a name="HC007012"></a> <br><a name="P007010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Self-induced starvation leading to PEM (<span>[[Fig. 7-2|Figure 7-2]]</span>)</li><li>Distorted body image
<blockquote style="color: blue; ">Anorexia nervosa: distorted body image</blockquote></li> </ol><li>Clinical findings</li><ol type="a"> <li>Secondary amenorrhea</li><ul> <li>(1) Decreased gonadotropin-releasing hormone</li><ul> <li>Caused by excessive loss of body fat and weight
<blockquote style="color: blue; ">Anorexia nervosa: secondary amenorrhea; osteoporosis</blockquote></li> </ul><li>(2) Decreased serum gonadotropins produces hypoestrinism.</li> </ul><li>Osteoporosis</li><ul> <li>(1) Caused by hypoestrinism</li><ul> <li>Estrogen normally enhances osteoblastic activity and inhibits osteoclastic activity.</li> </ul><li>(2) Lack of estrogen leads to decreased osteoblastic activity and increased osteoclastic activity.</li> </ul><li>Increased lanugo (fine, downy hair)</li><li>Increased hormones associated with stress (e.g., cortisol, growth hormone)</li><li>Most common cause of death is ventricular arrhythmia
<blockquote style="color: blue; ">Most common cause of death in anorexia nervosa: ventricular arrhythmia</blockquote></li> </ol> </ol>
</div></html>
<html><a name="HC007013"></a> <br><a name="P007011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ul> <li>Bingeing with self-induced vomiting</li> </ul><li>Clinical findings</li><ol type="a"> <li>Complications of vomiting</li><ul> <li>(1) Acid injury to tooth enamel</li><li>(2) Hypokalemia and metabolic alkalosis
<blockquote style="color: blue; ">Vomiting in bulimia nervosa: produces hypokalemic metabolic alkalosis</blockquote></li> </ul><li>Ventricular arrhythmia is the most common cause of death.</li> </ol> </ol>
</div></html>
<html><a name="HC007014"></a> <br><a name="P007012"></a><div class="PA" style="color: black; "><ol type="1"> <li>Body mass index (BMI) ≥ 30 kg/m<sup>2</sup> (normal, 18.5-24.9 kg/m<sup>2</sup>)</li><ol type="a"> <li>BMI = weight (kg)/height (m<sup>2</sup>)
<blockquote style="color: blue; ">BMI: weight (kg)/height (m<sup>2</sup>)</blockquote></li><li>Other factors than body weight</li><ul> <li>(1) Excess fat in the waist and flanks is more important than an excess in the thighs and buttocks.</li><li>(2) Excess visceral fat in the abdominal cavity has greater significance than excess subcutaneous fat.
<blockquote style="color: blue; ">Obesity: abdominal visceral fat most important</blockquote></li><ul> <li>Magnetic resonance imaging is used to access the amount of visceral fat.</li> </ul> </ul> </ol><li>Pathogenesis</li><ol type="a"> <li>Genetic factors account for 50% to 80% of cases.</li><ul> <li>Examples-defects in the leptin gene, syndrome X (obesity, hypertension, diabetes)</li> </ul><li>Acquired causes</li><ul> <li>(1) Endocrine disorders-hypothyroidism, Cushing syndrome</li><li>(2) Hypothalamic lesions, menopause</li> </ul><li>Leptin</li><ul> <li>(1) Leptin is a hormone.
<blockquote style="color: blue; ">Leptin: hormone; maintains energy balance (intake and output)</blockquote></li><ul> <li>(a) Secreted by adipose tissue</li><li>(b) Maintains energy balance (intake and output)</li> </ul><li>(2) Leptin increases when adipose stores are adequate.
<blockquote style="color: blue; ">3500 calorie excess = 1 pound</blockquote></li><ul> <li>(a) Decreases food intake (inhibits satiety center)</li><li>(b) Increases energy expenditure (stimulates β-oxidation of fatty acids)</li> </ul><li>(3) Leptin decreases when adipose stores are inadequate.</li><ul> <li>(a) Increases food intake (stimulates the satiety center)</li><li>(b) Decreases energy expenditure (inhibits β-oxidation of fatty acids)</li> </ul><li>(4) Obesity related to leptin dysfunction may be caused by the following:
<blockquote style="color: blue; ">Leptin gene: often defective in obesity</blockquote></li><ul> <li>(a) Resistance to leptin effects</li><li>(b) Mutations resulting in inhibition of leptin release</li> </ul> </ul> </ol><li>Clinical findings (<span>[[Table 7-1|Table 7-1. CLINICAL FINDINGS ASSOCIATED WITH OBESITY]]</span>)
<blockquote style="color: blue; ">Obesity: ↑ adipose causes ↓ synthesis insulin receptors</blockquote></li> </ol>
</div></html>
![[7.IV.A.Anorexia nervosa]]
<<tiddler [[7.IV.A.Anorexia nervosa]]>>
![[7.IV.B.Bulimia nervosa]]
<<tiddler [[7.IV.B.Bulimia nervosa]]>>
![[7.IV.C.Obesity]]
<<tiddler [[7.IV.C.Obesity]]>>
<html><a name="HC007042"></a> <br><a name="P007040"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Sodium restriction: hypertension, heart failure, chronic liver/kidney disease</blockquote>
<ol type="1"> <li>Reduces blood pressure</li><li>Nonpharmacologic treatment</li><ol type="a"> <li>Essential hypertension</li><li>Congestive heart failure</li><li>Chronic renal disease</li><li>Cirrhosis</li> </ol> </ol>
</div></html>
<html><a name="HC007043"></a> <br><a name="P007041"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Protein-restricted diet: chronic renal failure, cirrhosis</blockquote>
<ul> <li>Reduces the formation of urea and ammonia</li><ol type="1"> <li>Chronic renal disease</li><ul> <li>Decreases urea load</li> </ul><li>Cirrhosis of liver</li><ol type="a"> <li>Dysfunctional urea cycle cannot metabolize ammonia.</li><li>Increased ammonia produces hepatic encephalopathy.</li> </ol> </ol> </ul>
</div></html>
![[7.IX.A.Sodium restriction]]
<<tiddler [[7.IX.A.Sodium restriction]]>>
![[7.IX.B.Protein-restricted diets]]
<<tiddler [[7.IX.B.Protein-restricted diets]]>>
<html><a name="HC007016"></a> <br><a name="P007014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Retinol</li><ol type="a"> <li>Derived from dietary β-carotenes and retinol esters</li><ul> <li>(1) Increased β-carotenes in the diet cause the skin to turn yellow.
<blockquote style="color: blue; ">β-carotenemia: yellow skin, white sclera</blockquote></li><li>(2) The sclera remains white, unlike in jaundice, in which the sclera is yellow.</li> </ul><li>Main transport and storage form of vitamin A</li> </ol><li>Retinal
<blockquote style="color: blue; ">Vitamin A: vision, cell differentiation, growth/reproduction</blockquote></li><ol type="a"> <li>Product of the oxidation of retinol</li><li>Component of the visual pigment rhodopsin</li> </ol><li>Sources of vitamin A</li><ol type="a"> <li>Preformed vitamin A in liver egg yolk, butter, and milk</li><li>β-Carotenes in dark-green and yellow vegetables</li> </ol><li>Functions of vitamin A
<blockquote style="color: blue; ">Night blindness: first sign of vitamin A deficiency</blockquote></li><ol type="a"> <li>Normal vision in reduced light</li><li>Potentiating differentiation of mucus-secreting epithelium</li><li>Stimulating the immune system</li><li>Growth and reproduction</li> </ol><li>Clinical uses of vitamin A</li><ol type="a"> <li>Treatment of acne (e.g., isotretinoin)
<blockquote style="color: blue; ">Vitamin A in treatment: acne, acute promyelocytic leukemia</blockquote></li><li>Treatment of acute promyelocytic leukemia (refer to <span macro="tag [[12 White Blood Cell Disorders]] [[Chapter 12]]"></span>)</li> </ol><li>Causes of deficiency</li><ol type="a"> <li>Diets lacking sufficient yellow and green vegetables</li><li>Fat malabsorption (e.g., celiac disease)</li> </ol><li>Causes of toxicity</li><ol type="a"> <li>Consumption of bear liver
<blockquote style="color: blue; ">Vitamin A toxicity: consumption of bear liver</blockquote></li><li>Megadoses of vitamin A</li><li>Treatment with isotretinoin</li> </ol> </ol>
</div></html>
<html><a name="HC007017"></a> <br><a name="P007015"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sources of vitamin D</li><ol type="a"> <li>Fish oil, egg yolk, liver</li><li>Fortified milk</li> </ol><li>Metabolism (<span>[[Fig. 7-3|Figure 7-3]]</span>)</li><ol type="a"> <li>Preformed vitamin D in the diet consists of cholecalciferol (fish) and ergocalciferol (plants).</li><li>Endogenous synthesis of vitamin D in the skin occurs by photoconversion of 7-dehydrocholesterol via sunlight.
<blockquote style="color: blue; ">Sunlight: major source of vitamin D</blockquote></li><li>Reabsorption occurs in the small intestine.</li><li>Liver hydroxylation to 25-hydroxyvitamin D (25-OH-D; calcidiol) occurs in the cytochrome P-450 system.
<blockquote style="color: blue; ">Vitamin D: liver and kidney hydroxylation</blockquote></li><li>Kidney hydroxylation by 1-α-hydroxylase produces 1,25-(OH)<sub>2</sub>-D (active form of vitamin D; calcitriol).</li><li>Calcitriol attaches to nuclear receptors in target tissues.</li> </ol><li>Functions
<blockquote style="color: blue; ">Vitamin D: bone mineralization; maintain serum calcium and phosphorus</blockquote></li><ol type="a"> <li>Maintenance of serum calcium and phosphorus</li><ul> <li>Increases reabsorption of calcium and phosphorus from the intestine</li> </ul><li>Required for mineralization of epiphyseal cartilage and osteoid matrix</li><ul> <li>(1) Receptor located on osteoblasts</li><li>(2) Stimulates release of alkaline phosphatase</li><li>(3) Alkaline phosphatase dephosphorylates pyrophosphate, which normally inhibits bone mineralization.</li> </ul><li>Stimulates macrophage stem cell conversion into osteoclasts</li> </ol><li>Causes of deficiency</li><ol type="a"> <li>Renal failure
<blockquote style="color: blue; ">Renal failure: most common cause of vitamin D deficiency</blockquote></li><ul> <li>Decrease in 1-α-hydroxylation</li> </ul><li>Inadequate exposure to sunlight</li><ul> <li>Decreased synthesis from 7-dehydrocholesterol</li> </ul><li>Fat malabsorption</li><ul> <li>Decreased reabsorption of vitamin D</li> </ul><li>Chronic liver disease</li><ul> <li>Decreased synthesis of 25-(OH)-D</li> </ul><li>Enzyme induction of the cytochrome P-450 enzyme system (e.g., alcohol)</li><ul> <li>Increased metabolism of 25-(OH)-D into inactive metabolite</li> </ul> </ol><li>Megadoses may cause toxicity.</li> </ol>
</div></html>
<html><a name="HC007018"></a> <br><a name="P007016"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sources</li><ul> <li>Nuts (almonds, seeds), green leafy vegetables, olives, vegetable oil, wheat germ</li> </ul><li>Serves as an antioxidant
<blockquote style="color: blue; ">Vitamin E: cell membrane antioxidant</blockquote></li><ol type="a"> <li>Protects cell membranes from lipid peroxidation from free radicals</li><li>Prevents oxidation of low-density lipoprotein to a free radical form</li> </ol><li>Deficiency is uncommon; may occur in a few disorders:
<blockquote style="color: blue; ">Vitamin E toxicity: ↓ synthesis vitamin K-dependent coagulation factors</blockquote></li><ol type="a"> <li>Fat malabsorption in children with cystic fibrosis</li><li>Abetalipoproteinemia</li> </ol><li>Megadoses may cause toxicity.</li> </ol>
</div></html>
<html><a name="HC007019"></a> <br><a name="P007017"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sources</li><ul> <li>Derived from endogenous bacteria (most common source), dark green vegetables</li> </ul><li>Activated by the liver microsomal enzyme epoxide reductase
<blockquote style="color: blue; ">Vitamin K: majority synthesized by colonic bacteria</blockquote></li><ul> <li>Anticoagulant effect of coumarin derivatives results from the inhibition of epoxide reductase.</li> </ul><li>Function (also refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>)</li><ol type="a"> <li>γ-Carboxylates glutamate residues in vitamin K-dependent procoagulants and anticoagulants (proteins C and S)</li><ul> <li>(1) Procoagulants include factors II (prothrombin), VII, IX, X.
<blockquote style="color: blue; ">Vitamin K: <b>γ</b>-carboxylates II, VII, IX, X</blockquote></li><li>(2) Procoagulants are nonfunctional.</li> </ul><li>γ-Carboxylation allows vitamin K-dependent procoagulants to bind to calcium in fibrin clot formation.</li> </ol><li>Causes of deficiency</li><ol type="a"> <li>Use of broad-spectrum antibiotics
<blockquote style="color: blue; ">Broad-spectrum antibiotics: most common cause of vitamin K deficiency in a hospital</blockquote></li><ul> <li>Destroy bacterial synthesis of vitamin K</li> </ul><li>Newborns</li><ul> <li>(1) Lack bacterial colonization of the bowel</li><li>(2) Must receive vitamin K at birth
<blockquote style="color: blue; ">Newborns: require vitamin K injection</blockquote></li><ul> <li>(a) Prevents hemorrhagic disease of the newborn</li><li>(b) Breast milk is deficient in vitamin K.</li> </ul> </ul><li>Coumarin derivatives/cirrhosis
<blockquote style="color: blue; ">Rat poison contains coumarin derivatives.</blockquote></li><ul> <li>Decreases epoxide reductase activation of vitamin K</li> </ul><li>Fat malabsorption</li><ul> <li>Decreased intestinal reabsorption of vitamin K</li> </ul> </ol><li>Toxicity caused by excessive intake of vitamin K is uncommon.</li> </ol>
</div></html>
<html><a name="HC007020"></a> <br><a name="P007018"></a><div class="PA" style="color: black; "><ul> <li><span>[[Table 7-2|Table 7-2. FAT-SOLUBLE VITAMINS: CLINICAL FINDINGS IN DEFICIENCY AND TOXICITY]]</span> summarizes clinical findings and toxicities of all fat-soluble vitamins (<span>[[Fig. 7-4A-C|Figure 7-4]]</span>).</li> </ul>
</div></html>
![[7.V.A.Vitamin A]]
<<tiddler [[7.V.A.Vitamin A]]>>
![[7.V.B.Vitamin D]]
<<tiddler [[7.V.B.Vitamin D]]>>
![[7.V.C.Vitamin E]]
<<tiddler [[7.V.C.Vitamin E]]>>
![[7.V.D.Vitamin K]]
<<tiddler [[7.V.D.Vitamin K]]>>
![[7.V.E.Summary]]
<<tiddler [[7.V.E.Summary]]>>
<html><a name="HC007022"></a> <br><a name="P007020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sources
<blockquote style="color: blue; ">Thiamine: present in outer shell and seed of grain</blockquote></li><ol type="a"> <li>Liver; eggs; whole grain cereal, rice, wheat</li><li>Outer layers of grain and the seed</li><ul> <li>Removal of the outer grain in the refining process (white rice, white bread) significantly lowers thiamine content.</li> </ul> </ol><li>Function
<blockquote style="color: blue; ">Thiamine: important in ATP synthesis</blockquote></li><ol type="a"> <li>Cofactor in biochemical reactions that produce adenosine triphosphate (ATP)</li><li>Example-pyruvate dehydrogenase-catalyzed conversion of pyruvate to acetyl CoA</li> </ol><li>Causes of deficiency
<blockquote style="color: blue; ">Chronic alcoholism: most common cause of thiamine deficiency in the United States</blockquote></li><ol type="a"> <li>Chronic alcoholism (in the United States)</li><li>Diet of nonenriched rice (in developing countries)</li> </ol> </ol>
</div></html>
<html><a name="HC007023"></a> <br><a name="P007021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sources</li><ul> <li>Liver, dairy products, nuts, green leafy vegetables, soybeans</li> </ul><li>Active forms include flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN).
<blockquote style="color: blue; ">Riboflavin: FAD and FMN in citric acid cycle</blockquote></li><ul> <li>Located in the citric acid cycle</li> </ul><li>Deficiency is caused by severe malnourishment.</li> </ol>
</div></html>
<html><a name="HC007024"></a> <br><a name="P007022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sources</li><ul> <li>Most animal products, fruits and vegetables, and seeds</li> </ul><li>Functions
<blockquote style="color: blue; ">Niacin: NAD and NADP cofactors</blockquote></li><ol type="a"> <li>Active forms of niacin</li><ul> <li>(1) Oxidized nicotinamide adenine dinucleotide (NAD)</li><li>(2) Oxidized nicotinamide adenine dinucleotide phosphate (NADP)</li> </ul><li>NAD and NADP are cofactors in oxidation-reduction reactions.</li> </ol><li>Causes of deficiency (pellagra)
<blockquote style="color: blue; ">Corn-based diets: deficient in tryptophan and niacin</blockquote></li><ol type="a"> <li>Diets deficient in niacin</li><ul> <li>(1) Corn-based diets</li><li>(2) Corn is deficient in tryptophan and niacin.</li> </ul><li>Deficiency of tryptophan</li><ul> <li>(1) Tryptophan is used to synthesize niacin.
<blockquote style="color: blue; ">Tryptophan: used to synthesize niacin</blockquote></li><li>(2) Causes of tryptophan deficiency</li><ul> <li>(a) Diets deficient in tryptophan
<blockquote style="color: blue; ">Trytophan deficiency: Hartnup disease, carcinoid syndrome</blockquote></li><li>(b) Hartnup disease</li><ul> <li>Inborn error of metabolism with inability to reabsorb tryptophan in the small bowel and kidneys</li> </ul><li>(c) Carcinoid syndrome</li><ul> <li>Tryptophan is used up in synthesizing serotonin.
<blockquote style="color: blue; ">Three Ds of pellagra: dermatitis, diarrhea, dementia</blockquote></li> </ul> </ul> </ul> </ol><li>Excessive intake of niacin</li><ol type="a"> <li>Leads to flushing caused by vasodilation</li><ul> <li>Adverse effect of nicotinic acid, a lipid-lowering drug</li> </ul><li>Intrahepatic cholestasis</li> </ol> </ol>
</div></html>
<html><a name="HC007025"></a> <br><a name="P007023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Sources</li><ul> <li>Meats, fish, seeds, wheat germ, and whole-grain flour
<blockquote style="color: blue; ">Pyridoxine: heme synthesis, transamination, neurotransmitters</blockquote></li> </ul><li>Functions</li><ul> <li>Required for transamination, heme synthesis, and neurotransmitter synthesis</li> </ul><li>Causes of deficiency
<blockquote style="color: blue; ">Isoniazid therapy: most common cause pyridoxine deficiency</blockquote></li><ol type="a"> <li>Isoniazid (used in treating tuberculosis)</li><li>Goat milk, chronic alcoholism</li> </ol> </ol>
</div></html>
<html><a name="HC007026"></a><span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span> <br> <br><a name="P007024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Present only in animal products (eggs, meat, dairy products)
<blockquote style="color: blue; ">Vitamin B<sub>12</sub>: only in animal products</blockquote></li><li>Requires intrinsic factor for reabsorption in the terminal ileum</li><li>Functions</li><ol type="a"> <li>DNA synthesis
<blockquote style="color: blue; ">Vitamin B<sub>12</sub>: DNA synthesis; odd-chain fatty acid synthesis</blockquote></li><li>Propionate (odd-chain fatty acid) metabolism</li> </ol><li>Causes of deficiency</li><ol type="a"> <li>Strict vegan diet</li><li>Pernicious anemia
<blockquote style="color: blue; ">Pernicious anemia: most common cause of vitamin B<sub>12</sub> deficiency</blockquote></li><li>Terminal ileal disease (e.g., Crohn's disease), bacterial overgrowth</li> </ol> </ol>
</div></html>
<html><a name="HC007027"></a><span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span> <br> <br><a name="P007025"></a><div class="PA" style="color: black; "><ol type="1"> <li>Present in most foods
<blockquote style="color: blue; ">Folic acid: DNA synthesis</blockquote></li><li>Function</li><ul> <li>DNA synthesis</li> </ul><li>Causes of deficiency
<blockquote style="color: blue; ">Goat milk: lacks folate and pyridoxine</blockquote></li><ol type="a"> <li>Dietary deficiency</li><ul> <li>Elderly individuals, goat milk</li> </ul><li>Drugs
<blockquote style="color: blue; ">Alcohol excess: most common cause folate deficiency</blockquote></li><ul> <li>Alcohol, methotrexate, phenytoin, oral contraceptives, trimethoprim, 5-fluorouracil</li> </ul><li>Malabsorption, overutilization (e.g., pregnancy)</li> </ol> </ol>
</div></html>
<html><a name="HC007028"></a> <br><a name="P007026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Present in most foods</li><li>Function</li><ol type="a"> <li>Cofactor in carboxylase reactions</li><li>Example-pyruvate carboxylase-catalyzed conversion of pyruvate to oxaloacetate</li> </ol><li>Causes of deficiency</li><ol type="a"> <li>Eating raw eggs (avidin binds biotin)</li><li>Taking antibiotics
<blockquote style="color: blue; ">Biotin deficiency: eating raw eggs</blockquote></li> </ol> </ol>
</div></html>
<html><a name="HC007029"></a> <br><a name="P007027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Functions</li><ol type="a"> <li>Hydroxylation of lysine and proline residues in collagen synthesis
<blockquote style="color: blue; ">Ascorbic acid: collagen synthesis, antioxidant, reducing agent</blockquote></li><ul> <li>(1) Deficiency leads to collagen with reduced tensile strength.</li><li>(2) Hydroxylation sites are anchors for cross-linking of tropocollagens.</li> </ul><li>Antioxidant activity</li><ul> <li>(1) Regenerates vitamin E and reduces oxidation of low-density lipoprotein</li><li>(2) Best vitamin to neutralize hydroxyl free radicals</li> </ul><li>Reduces nonheme iron (3 valence) from plants to the ferrous (2 valence) state for reabsorption in the duodenum</li><ul> <li>Deficiency may produce iron deficiency (microcytic anemia).</li> </ul><li>Keeps tetrahydrofolate (FH<sub>4</sub>) in its reduced form</li><ul> <li>Deficiency may produce folate deficiency (macrocytic anemia).</li> </ul><li>Cofactor in the conversion of dopamine to norepinephrine in catecholamine synthesis
<blockquote style="color: blue; ">Ascorbic acid: cofactor conversion dopamine to norepinephrine</blockquote></li> </ol><li>Causes of deficiency</li><ol type="a"> <li>Diets lacking fruits and vegetables</li><li>Cigarette smoking</li><ul> <li>Used up in neutralizing free radicals in cigarette smoke
<blockquote style="color: blue; ">Scurvy: deficiency of ascorbic acid</blockquote></li> </ul> </ol><li>Excess intake (hypervitaminosis C) may lead to the formation of renal calculi composed of uric acid.</li> </ol>
</div></html>
<html><a name="HC007030"></a> <br><a name="P007028"></a><div class="PA" style="color: black; "><ul> <li><span>[[Table 7-3|Table 7-3. WATER-SOLUBLE VITAMINS: CLINICAL FINDINGS IN DEFICIENCY]]</span> summarizes the clinical findings in the water-soluble vitamin deficiencies (<span>[[Fig. 7-5A-D|Figure 7-5]]</span>).</li> </ul>
</div></html>
![[7.VI.A.Thiamine (vitamin B1)]]
<<tiddler [[7.VI.A.Thiamine (vitamin B1)]]>>
![[7.VI.B.Riboflavin (vitamin B2)]]
<<tiddler [[7.VI.B.Riboflavin (vitamin B2)]]>>
![[7.VI.C.Niacin (vitamin B3, nicotinic acid)]]
<<tiddler [[7.VI.C.Niacin (vitamin B3, nicotinic acid)]]>>
![[7.VI.D.Pyridoxine (vitamin B6)]]
<<tiddler [[7.VI.D.Pyridoxine (vitamin B6)]]>>
![[7.VI.E.Cobalamin (vitamin B12) (refer to Chapter 11)]]
<<tiddler [[7.VI.E.Cobalamin (vitamin B12) (refer to Chapter 11)]]>>
![[7.VI.F.Folic acid (refer to Chapter 11)]]
<<tiddler [[7.VI.F.Folic acid (refer to Chapter 11)]]>>
![[7.VI.G.Biotin]]
<<tiddler [[7.VI.G.Biotin]]>>
![[7.VI.H.Ascorbic acid (vitamin C)]]
<<tiddler [[7.VI.H.Ascorbic acid (vitamin C)]]>>
![[7.VI.I.Summary]]
<<tiddler [[7.VI.I.Summary]]>>
<html><a name="HC007032"></a> <br><a name="P007032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Functions</li><ol type="a"> <li>Cofactor for metalloenzymes (e.g., collagenase in wound remodeling)</li><li>Growth and spermatogenesis in children</li> </ol><li>Causes of zinc deficiency</li><ol type="a"> <li>Alcoholism, diabetes mellitus, chronic diarrhea</li><li>Acrodermatitis enteropathica</li><ul> <li>(1) Autosomal recessive disease</li><li>(2) Dermatitis, growth retardation, decreased spermatogenesis, poor wound healing</li> </ul> </ol><li>Clinical findings in zinc deficiency (<span>[[Table 7-4|Table 7-4. TRACE METALS: CLINICAL FINDINGS IN DEFICIENCY]]</span>)
<blockquote style="color: blue; ">Zinc deficiency: poor wound healing, dysgeusia, perioral rash</blockquote></li> </ol>
</div></html>
<html><a name="HC007033"></a> <br><a name="P007033"></a><div class="PA" style="color: black; "><ol type="1"> <li>Functions as a cofactor</li><ol type="a"> <li>Ferroxidase (binds iron to transferrin)</li><li>Lysyl oxidase (cross-linking of collagen and elastic tissue)</li><li>Tyrosinase (melanin synthesis)</li> </ol><li>Copper deficiency</li><ul> <li>Most often due to total parenteral nutrition (TPN)</li> </ul><li>Clinical findings in copper deficiency (see <span>[[Table 7-4|Table 7-4. TRACE METALS: CLINICAL FINDINGS IN DEFICIENCY]]</span>)</li><li>Copper excess, Wilson's disease
<blockquote style="color: blue; ">Copper excess: Wilson's disease</blockquote></li><ol type="a"> <li>Autosomal recessive disease</li><li>Defect in eliminating copper into bile</li><li>Defect in incorporating copper into ceruloplasmin (binding protein for copper)</li><li>Chronic liver disease, Kayser-Fleischer ring in cornea, basal ganglia degeneration</li> </ol> </ol>
</div></html>
<html><a name="HC007034"></a> <br><a name="P007034"></a><div class="PA" style="color: black; "><ol type="1"> <li>Function</li><ul> <li>Synthesis of thyroid hormone</li> </ul><li>Iodine deficiency</li><ul> <li>Most often due to inadequate intake of iodized table salt</li> </ul><li>Clinical findings in iodide deficiency (see <span>[[Table 7-4|Table 7-4. TRACE METALS: CLINICAL FINDINGS IN DEFICIENCY]]</span>)
<blockquote style="color: blue; ">Iodide deficiency: multinodular goiter</blockquote></li> </ol>
</div></html>
<html><a name="HC007035"></a> <br><a name="P007035"></a><div class="PA" style="color: black; "><ol type="1"> <li>Functions</li><ol type="a"> <li>Component of glucose tolerance factor (maintains a normal glucose)</li><li>Cofactor for insulin that facilitates binding of glucose to adipose and muscle
<blockquote style="color: blue; ">Chromium: useful in diabetics</blockquote></li> </ol><li>Chromium deficiency</li><ul> <li>Most often due to TPN</li> </ul><li>Clinical findings in chromium deficiency (see <span>[[Table 7-4|Table 7-4. TRACE METALS: CLINICAL FINDINGS IN DEFICIENCY]]</span>)</li> </ol>
</div></html>
<html><a name="HC007036"></a> <br><a name="P007036"></a><div class="PA" style="color: black; "><ol type="1"> <li>Component of glutathione peroxidase</li><ul> <li>Antioxidant that converts peroxide to water using reduced glutathione (GSH)
<blockquote style="color: blue; ">Selenium: antioxidant</blockquote></li> </ul><li>Selenium deficiency</li><ul> <li>Most often due to TPN</li> </ul><li>Clinical findings in selenium deficiency (see <span>[[Table 7-4|Table 7-4. TRACE METALS: CLINICAL FINDINGS IN DEFICIENCY]]</span>)</li> </ol>
</div></html>
<html><a name="HC007037"></a> <br><a name="P007037"></a><div class="PA" style="color: black; "><ol type="1"> <li>Function</li><ul> <li>Component of calcium hydroxyapatite in bone and teeth</li> </ul><li>Fluoride deficiency
<blockquote style="color: blue; ">Fluoride: component of calcium hydroxyapatite</blockquote></li><ul> <li>Most often due to inadequate intake of fluoridated water</li> </ul><li>Fluoride excess</li><ol type="a"> <li>Chalky deposits on the teeth</li><li>Calcification of ligaments</li><li>Increased risk for bone fractures
<blockquote style="color: blue; ">Fluoride deficiency: dental caries</blockquote></li> </ol><li>Clinical findings in fluoride deficiency (see <span>[[Table 7-4|Table 7-4. TRACE METALS: CLINICAL FINDINGS IN DEFICIENCY]]</span>)</li> </ol>
</div></html>
![[7.VII.A.Zinc]]
<<tiddler [[7.VII.A.Zinc]]>>
![[7.VII.B.Copper]]
<<tiddler [[7.VII.B.Copper]]>>
![[7.VII.C.Iodine]]
<<tiddler [[7.VII.C.Iodine]]>>
![[7.VII.D.Chromium]]
<<tiddler [[7.VII.D.Chromium]]>>
![[7.VII.E.Selenium]]
<<tiddler [[7.VII.E.Selenium]]>>
![[7.VII.F.Fluoride]]
<<tiddler [[7.VII.F.Fluoride]]>>
<html><a name="HC007039"></a> <br><a name="P007038"></a><div class="PA" style="color: black; "><ol type="1"> <li>Insoluble fiber
<blockquote style="color: blue; ">Fiber types: insoluble, soluble</blockquote></li><ol type="a"> <li>Nonfermentable</li><ul> <li>Examples-wheat bran, wheat germ</li> </ul><li>Absorbs water</li><li>Binds potential carcinogens</li><ul> <li>(1) Lithocholic acid</li><ul> <li>(a) Only bile acid that is <i>not</i> reabsorbed in the terminal ileum</li><li>(b) May have causative role in producing colorectal cancer</li> </ul><li>(2) Estrogen</li><ul> <li>Unopposed increase in estrogen increases risk for endometrial and breast cancer.</li> </ul> </ul><li>Stool eliminated faster</li> </ol><li>Soluble fiber
<blockquote style="color: blue; ">Soluble fiber: lowers cholesterol</blockquote></li><ol type="a"> <li>Fermentable</li><ul> <li>Examples-oat bran, psyllium seeds, fruits</li> </ul><li>Decreases serum cholesterol</li><li>Increases fecal bacterial mass</li> </ol><li>Benefits of increased fiber</li><ol type="a"> <li>Reduces deconjugation of estrogen delivered in bile</li><ul> <li>Decreases reabsorption of estrogen, which decreases risk for estrogen-related cancers</li> </ul><li>Decreases risk for developing diverticulosis by preventing constipation</li><li>May reduce the risk for developing colorectal and estrogen-related cancers</li><li>Decreases risk for developing heart disease</li><ul> <li>Decreases cholesterol
<blockquote style="color: blue; ">Fiber: ↓ risk for sigmoid diverticulosis, certain cancers, heart disease</blockquote></li> </ul> </ol> </ol>
</div></html>
<html><a name="HC007040"></a> <br><a name="P007039"></a><div class="PA" style="color: black; "><ul> <li>20 to 30 g of fiber/day</li> </ul>
</div></html>
![[7.VIII.A.Types/function]]
<<tiddler [[7.VIII.A.Types/function]]>>
![[7.VIII.B.Recommendation for fiber in diet]]
<<tiddler [[7.VIII.B.Recommendation for fiber in diet]]>>
<html><a name="HC008002"></a> <br><a name="P008001"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Benign tumors: epithelial or connective tissue origin</blockquote>
<ol type="1"> <li>Suffix "oma" generally indicates a benign tumor.</li><li>Benign tumors of epithelial origin</li><ol type="a"> <li>Arise from ectoderm or endoderm
<blockquote style="color: blue; ">Epothelial tissue origin: ectoderm, endoderm</blockquote></li><li>Example-tubular adenoma (adenomatous polyp) arising from glands in the colon (<span>[[Fig. 8-1A|Figure 8-1]]</span>; see <span>[[Fig. 17-37|Figure 17-37]]</span>)</li> </ol><li>Benign tumors of connective tissue origin arise from mesoderm.
<blockquote style="color: blue; ">Connective tissue origin: mesoderm</blockquote></li><ul> <li>Example-lipoma from adipose (<span>[[Fig. 8-1B|Figure 8-1]]</span>)</li> </ul><li>Tumors that are usually benign</li><ol type="a"> <li>Mixed tumors</li><ul> <li>(1) Neoplastic cells have two different morphologic patterns but derive from the same germ cell layer.</li><li>(2) Example-pleomorphic adenoma of the parotid gland</li> </ul><li>Teratomas</li><ul> <li>(1) Tumors that derive from more than one germ cell layer
<blockquote style="color: blue; ">Teratoma: derives from ectoderm, endoderm, mesoderm</blockquote></li><ul> <li>Contain tissue derived from ectoderm, endoderm, and mesoderm (<span>[[Fig. 8-1C|Figure 8-1]]</span>)</li> </ul><li>(2) Sites</li><ul> <li>Ovaries, testes, anterior mediastinum, and pineal gland</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC008003"></a> <br><a name="P008002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Carcinomas
<blockquote style="color: blue; ">Carcinomas: derive from squamous, glandular (adenocarcinoma), transitional epithelium</blockquote></li><ol type="a"> <li>Derive from epithelial tissue-squamous, glandular, transitional</li><li>Sites of squamous cell carcinoma (<span>[[Fig. 8-1D|Figure 8-1]]</span>)</li><ul> <li>Oropharynx, larynx, upper/middle esophagus, lung, cervix, skin</li> </ul><li>Sites of adenocarcinoma (glandular epithelium; <span>[[Fig. 8-1E|Figure 8-1]]</span>)</li><ul> <li>Lung, distal esophagus to rectum, pancreas, liver, breast, endometrium, ovaries, kidneys, prostate</li> </ul><li>Sites of transitional cell carcinoma</li><ul> <li>Urinary bladder, ureter, renal pelvis</li> </ul> </ol><li>Sarcomas
<blockquote style="color: blue; ">Sarcomas: derive from connective tissue</blockquote></li><ol type="a"> <li>Derive from connective tissue</li><li>Example-osteogenic sarcoma in bone (<span>[[Fig. 8-1F|Figure 8-1]]</span>)</li> </ol> </ol>
</div></html>
<html><a name="HC008004"></a> <br><a name="P008003"></a><div class="PA" style="color: black; "><ol type="1"> <li>Hamartoma
<blockquote style="color: blue; ">Hamartoma: non-neoplastic overgrowth of tissue</blockquote></li><ol type="a"> <li>Non-neoplastic overgrowth of disorganized tissue indigenous to a particular site</li><li>Examples-bronchial hamartoma (contains cartilage), Peutz-Jeghers polyp</li> </ol><li>Choristoma (heterotopic rest)
<blockquote style="color: blue; ">Choristoma: normal tissue where it should <i>not</i> be</blockquote></li><ol type="a"> <li>Non-neoplastic normal tissue in a foreign location</li><li>Examples-pancreatic tissue in the stomach wall; parietal cells in Meckel diverticulum</li> </ol> </ol>
</div></html>
![[8.I.A.Benign tumors]]
<<tiddler [[8.I.A.Benign tumors]]>>
![[8.I.B.Malignant tumors (cancer)]]
<<tiddler [[8.I.B.Malignant tumors (cancer)]]>>
![[8.I.C.Tumor-like conditions]]
<<tiddler [[8.I.C.Tumor-like conditions]]>>
<html><a name="HC008006"></a> <br><a name="P008004"></a><div class="PA" style="color: black; "><ol type="1"> <li>Parenchyma
<blockquote style="color: blue; ">Parenchyma: neoplastic component</blockquote></li><ul> <li>Neoplastic component that determines the tumor's biologic behavior</li> </ul><li>Stroma</li><ol type="a"> <li>Non-neoplastic supportive tissue</li><li>Most infiltrating carcinomas induce production of a dense, fibrous stroma</li> </ol> </ol>
</div></html>
<html><a name="HC008007"></a> <br><a name="P008005"></a><div class="PA" style="color: black; "><ol type="1"> <li>Benign tumors</li><ul> <li>Usually well differentiated (resemble parent tissue)</li> </ul><li>Malignant tumors</li><ol type="a"> <li>Well differentiated or low grade
<blockquote style="color: blue; ">Grade of cancer: does the cancer resemble its parent tissue or not?</blockquote></li><ul> <li>(1) Resemble parent tissue</li><li>(2) Example-produce keratin pearls or glandular lumens with secretions (see <span>[[Fig. 8-1D and E|Figure 8-1]]</span>)</li> </ul><li>Poorly differentiated, high grade, or anaplastic</li><ul> <li>No differentiating features</li> </ul><li>Intermediate grade</li><ul> <li>Features are between low- and high-grade cancer.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC008008"></a> <br><a name="P008006"></a><div class="PA" style="color: black; "><ol type="1"> <li>Benign tumors</li><ol type="a"> <li>Nuclear/cytoplasmic ratio is close to normal.</li><li>Mitoses have normal mitotic spindles.
<blockquote style="color: blue; ">Malignant tumors: ↑ nuclear/cytoplasmic ratio; abnormal mitotic spindles</blockquote></li><li>Nuclear/cytoplasmic ratio is increased, and nucleoli are prominent.</li><li>Mitoses have normal and atypical mitotic spindles.</li> </ol> </ol>
</div></html>
<html><a name="HC008009"></a> <br><a name="P008007"></a><div class="PA" style="color: black; "><ol type="1"> <li>Benign tumors usually have a slow growth rate.</li><li>Malignant tumors have a variable growth rate.</li><ol type="a"> <li>Correlates with the degree of differentiation</li><li>Anaplastic (high-grade) cancers have an increased growth rate.</li> </ol><li>Thirty doubling times are required for a tumor to be clinically evident.
<blockquote style="color: blue; ">Malignant tumors: 30 doubling times before detected</blockquote></li><ul> <li>Equivalent to 10<sup>9</sup> cells, 1 g of tissue, volume of 1 mL</li> </ul><li>Malignant cells in the cell cycle are primarily targeted by chemotherapy.</li><ol type="a"> <li>DNA is exposed and is susceptible to damage by drugs and radiation causing the cells to die.</li><li>Loss of the cells causes more cancer cells to go into the cell cycle; hence debulking the tumor as these cells also get destroyed.</li> </ol> </ol>
</div></html>
<html><a name="HC008010"></a> <br><a name="PB008001"></a><div class="BB" style="color: rgb(47, 79, 79); ">The <b>monoclonal origin</b> of neoplasms has been shown by studying glucose-6-phosphate dehydrogenase (G6PD) isoenzymes A and B in selected neoplasms (e.g., leiomyoma of the uterus). All the neoplastic smooth muscle cells in uterine leiomyomas have either the A or the B G6PD isoenzyme. Non-neoplastic smooth muscle proliferations in the uterus (e.g., pregnant uterus) have some cells with the A isoenzyme and others with the B isoenzyme, indicating their polyclonal origin.</div><a name="P008008"></a><div class="PA" style="color: black; "><ol type="1"> <li>Benign and malignant tumors derive from a single precursor cell.
<blockquote style="color: blue; ">Benign and malignant tumors: monoclonal</blockquote></li><li>Non-neoplastic proliferations derive from multiple cells (polyclonal).</li> </ol>
</div></html>
<html><a name="HC008011"></a> <br><a name="P008009"></a><div class="PA" style="color: black; "><ol type="1"> <li>Telomerase function</li><ol type="a"> <li>Preserves length of telomeres</li><ul> <li>Sequences of nontranscribed DNA at the ends of chromosomes</li> </ul><li>Prevents gene loss after multiple cell divisions</li> </ol><li>Benign tumors have normal telomerase activity.</li><li>Malignant tumors have upregulation of telomerase activity.
<blockquote style="color: blue; ">Malignant tumors: upregulation telomerase activity</blockquote></li><ul> <li>They do <i>not</i> lose genetic material after multiple cell divisions.</li> </ul> </ol>
</div></html>
<html><a name="HC008012"></a> <br><a name="P008010"></a><div class="PA" style="color: black; "><ol type="1"> <li>Benign tumors</li><ol type="a"> <li>They do <i>not</i> invade.</li><li>They are usually enclosed by a fibrous capsule.</li><ul> <li>Exception-uterine leiomyomas do <i>not</i> have a fibrous tissue capsule.</li> </ul> </ol><li>Malignant tumors invade tissue.
<blockquote style="color: blue; ">Basal cell carcinomas of the skin: invade tissue but do <i>not</i> metastasize</blockquote></li><li>Some tissues resist invasion.</li><ul> <li>Examples-mature cartilage, elastic tissue in arteries</li> </ul><li>Sequence of invasion by malignant tumors
<blockquote style="color: blue; ">Invasion: second most important criterion for malignancy</blockquote></li><ol type="a"> <li>Loss of intercellular adherence</li><ul> <li>E-cadherin (intercellular adhesion agent) is <i>not</i> produced.</li> </ul><li>Cell invasion occurs.
<blockquote style="color: blue; ">Resist invasion: cartilage, elastic tissue</blockquote></li><ul> <li>(1) Cell receptors attach to laminin (glycoprotein in the basement membrane).</li><li>(2) Cells release type IV collagenase (metalloproteinase containing zinc).
<blockquote style="color: blue; ">Loss of intercellular aherence → cell invasion</blockquote></li><ul> <li>Dissolves the basement membrane</li> </ul><li>(3) Cell receptors attach to fibronectin in the extracellular matrix.</li><li>(4) Cells produce cytokines (stimulate locomotion) and proteases (dissolve connective tissue).</li><li>(5) Cells produce factors that stimulate angiogenesis.</li><ul> <li>Secrete vascular endothelial growth factor and basic fibroblast growth factor</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC008013"></a> <br><a name="PB008002"></a><div class="BB" style="color: rgb(47, 79, 79); ">Regional lymph nodes are the first line of defense against the spread of a carcinoma. However, if the nodal architecture is destroyed, malignant cells enter the efferent lymphatics, which empty into the bloodstream. In the bloodstream, malignant cells metastasize to distant organ sites (e.g., liver, lungs, bone).</div><a name="PB008003"></a><div class="BB" style="color: rgb(47, 79, 79); ">Some carcinomas have both lymphatic and hematogenous spread. Renal cell carcinomas commonly invade the renal vein, where the tumor has the potential for extending into the vena cava to as far as the right side of the heart. Hepatocellular carcinomas invade the portal and hepatic veins. Tumor obstruction of either vein produces portal hypertension, splenomegaly, and ascites.</div><a name="P008011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Benign tumors do <i>not</i> metastasize.</li><li>Malignant tumors metastasize.</li><li>Pathways of dissemination</li><ol type="a"> <li>Lymphatic spread to lymph nodes</li><ul> <li>Usual mechanism of dissemination of carcinomas
<blockquote style="color: blue; ">Extranodal metastasis (e.g., liver) has greater prognostic significance than nodal metastasis.</blockquote></li> </ul><li>Hematogenous spread
<blockquote style="color: blue; ">Lymph nodes: first line of defense in carcinomas</blockquote></li><ul> <li>(1) Usual mechanism of dissemination for sarcomas</li><li>(2) Cells entering the portal vein metastasize to the liver.</li><li>(3) Cells entering the vena cava metastasize to the lungs.</li> </ul><li>Seeding
<blockquote style="color: blue; ">Routes of metastasis: lymphatic, hematogenous, seeding of body cavities</blockquote></li><ul> <li>Malignant cells exfoliate from a surface and implant and invade tissue in a body cavity.</li> </ul><ul> <li>(1) Primary surface-derived ovarian cancers (e.g., serous cystadenocarcinoma) commonly seed the omentum.
<blockquote style="color: blue; ">Seeding: common with surface-derived ovarian cancers</blockquote></li><li>(2) Peripherally located lung cancers commonly seed the parietal and visceral pleurae.</li><li>(3) Glioblastoma multiforme commonly seeds the cerebrospinal fluid causing spread to the brain and spinal cord.</li> </ul> </ol><li>Bone metastasis
<blockquote style="color: blue; ">Bone metastasis: vertebra most common site; paravertebral venous plexus</blockquote></li><ol type="a"> <li>Vertebral column</li><ul> <li>(1) Most common metastatic site in bone (<span>[[Fig. 8-2A|Figure 8-2]]</span>)</li><li>(2) Due to the Batson paravertebral venous plexus</li><ul> <li>It has connections with the vena cava and the vertebral bodies.</li> </ul> </ul><li>Osteoblastic metastases
<blockquote style="color: blue; ">Osteoblastic metastasis: ↑ serum alkaline phosphatase</blockquote></li><ul> <li>(1) Increased serum alkaline phosphatase indicates reactive bone formation (<span>[[Fig. 8-2B|Figure 8-2]]</span>).</li><li>(2) Radiodensities are seen on radiographs (e.g., prostate cancer; <span>[[Fig. 8-2C|Figure 8-2]]</span>).</li> </ul><li>Osteolytic metastases</li><ul> <li>(1) Radiolucencies are seen on radiographs (e.g., lung cancer; <span>[[Fig. 8-2D|Figure 8-2]]</span>).</li><li>(2) Pathogenesis</li><ul> <li>(a) Tumor may produce substances that locally activate osteoclasts producing lytic lesions.</li><ul> <li>Example-prostaglandin E<sub>2</sub>, interleukin 1</li> </ul><li>(b) Tumor produces parathyroid hormone (PTH)-related protein; no lytic lesions due to generalized increase in osteoclast activity
<blockquote style="color: blue; ">Osteolytic metastasis: potential for hypercalcemia, pathologic fractures</blockquote></li><ul> <li>Examples-squamous cell carcinoma in the lung, renal cell carcinoma</li> </ul> </ul><li>(3) Potential consequences of osteolytic metastases
<blockquote style="color: blue; ">Bone metastasis: osteoblastic (radiodense) or osteolytic (radiolucent).</blockquote></li><ul> <li>(a) Pathologic fractures</li><li>(b) Hypercalcemia</li> </ul> </ul><li>Pain in bone metastasis is treated with local radiation therapy.</li> </ol><li>Metastasis is often more common than a primary cancer in:</li><ol type="a"> <li>Lymph nodes (e.g., metastatic breast and lung cancer)
<blockquote style="color: blue; ">Lymph node: most common tissue metastasized to</blockquote></li><li>Lungs (e.g., metastatic breast cancer)</li><li>Liver (e.g., metastatic lung cancer) (<span>[[Fig. 8-2E|Figure 8-2]]</span>)</li><li>Bone (e.g., metastatic breast cancer)</li><li>Brain (e.g., metastatic lung cancer)</li> </ol> </ol>
</div></html>
![[8.II.A.Components of benign and malignant tumors]]
<<tiddler [[8.II.A.Components of benign and malignant tumors]]>>
![[8.II.B.Differentiation]]
<<tiddler [[8.II.B.Differentiation]]>>
![[8.II.C.Nuclear features]]
<<tiddler [[8.II.C.Nuclear features]]>>
![[8.II.D.Growth rate]]
<<tiddler [[8.II.D.Growth rate]]>>
![[8.II.E.Monoclonality]]
<<tiddler [[8.II.E.Monoclonality]]>>
![[8.II.F.Telomerase activity]]
<<tiddler [[8.II.F.Telomerase activity]]>>
![[8.II.G.Local invasion]]
<<tiddler [[8.II.G.Local invasion]]>>
![[8.II.H.Metastasis]]
<<tiddler [[8.II.H.Metastasis]]>>
<html><a name="HC008015"></a> <br><a name="P008014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Cancer is the second most common cause of death in the United States.
<blockquote style="color: blue; ">Cancer: 2nd most common cause death in US</blockquote></li><li>Causes</li><ol type="a"> <li>External factors</li><ul> <li>Tobacco, alcohol, chemicals, radiation, pathogens</li> </ul><li>Internal factors</li><ul> <li>Hormones, immune conditions, inherited mutations</li> </ul> </ol><li>Risk for developing cancer increases with age.</li><ul> <li>More than 75% of cancers are in persons 55 and older.</li> </ul><li>Lifetime risk</li><ol type="a"> <li>Probability that a person will develop or die from cancer</li><li>In the United States, men have slightly less than 1 in 2 lifetime risk
<blockquote style="color: blue; ">Lifetime risk for cancer: men > women</blockquote></li><li>In the United States, women have a little more than 1 in 3 lifetime risk</li> </ol><li>Relative risk</li><ol type="a"> <li>Measure of the strength of a relationship between risk factors and a particular cancer</li><li>Compares risk of developing cancer in individuals at risk with those that are not</li><ul> <li>(1) Compares risk for cancer in male smokers versus nonsmokers</li><li>(2) Male smokers have 23 times greater risk than male nonsmokers; relative risk is 23.</li><li>(3) Women with a history of breast cancer in a first-degree relative (mother, sister, daughter) have a two times greater risk for developing breast cancer (relative risk is 2).</li> </ul> </ol><li>Relative survival rates</li><ol type="a"> <li>Refers to percentage of cancer patients alive after a period of time (usually 5 years) relative to persons without cancer</li><li>Should be interpreted with caution, because some cancers commonly recur after 5 years.</li><ul> <li>Examples-breast, kidney</li> </ul> </ol><li>Blacks
<blockquote style="color: blue; ">Blacks: greatest overall risk for cancer</blockquote></li><ol type="a"> <li>Greatest risk for cancer and cancer-related deaths of any other racial group or ethnicity</li><li>Applies to almost all cancers <i>except</i> malignant melanoma</li> </ol><li>Hispanics and Asians</li><ol type="a"> <li>Lower incidence rates for all cancers combined than whites</li><li>Exceptions are for cancers associated with infections-cervix (human papillomavirus), liver (hepatitis B and C), stomach (<i>Helicobacter pylori</i>)</li> </ol><li>Native Americans</li><ul> <li>Highest incidence and cancer-related deaths due to kidney cancer than all racial and ethnic populations.</li> </ul> </ol>
</div></html>
<html><a name="HC008016"></a> <br><a name="P008015"></a><div class="PA" style="color: black; "><ol type="1"> <li>Cancers in children</li><ol type="a"> <li>Second most common cause of death in children (accidents most common cause)
<blockquote style="color: blue; ">Most common cancer in children: acute lymphoblastic leukemia</blockquote></li><li>Acute lymphoblastic leukemia (∼33%), central nervous system (CNS) tumors (∼21%), neuroblastoma (∼7%), Wilms' tumor (∼5%)</li><ul> <li>These are <i>not</i> common tumors in adults.</li> </ul> </ol><li>Cancers in men (in decreasing order)
<blockquote style="color: blue; ">Cancer in men: prostate, lung, colorectal Cancer in women: breast, lung, colorectal</blockquote></li><ul> <li>Prostate, lung, colorectal</li> </ul><li>Cancers in women (in decreasing order)</li><ul> <li>Breast, lung, colorectal</li> </ul><li>Gynecologic cancers (in descending order)
<blockquote style="color: blue; ">Gynecologic cancer: endometrium, ovary, cervical</blockquote></li><ol type="a"> <li>Endometrium</li><li>Ovarian</li><li>Cervical</li><ul> <li>Least common due to cervical Pap smears detecting dysplasia</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC008017"></a> <br><a name="P008016"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Most common cause of cancer death in adults: lung cancer</blockquote>
<ol type="1"> <li>Cancer-related deaths in men (in decreasing order)</li><ul> <li>Lung, prostate, colorectal</li> </ul><li>Cancer-related deaths in women (in decreasing order)</li><ul> <li>Lung, breast, colorectal</li> </ul><li>Gynecologic cancer-related deaths (in descending order)</li><ol type="a"> <li>Endometrium</li><li>Ovary</li><li>Cervix</li> </ol> </ol>
</div></html>
![[8.III.A.General]]
<<tiddler [[8.III.A.General]]>>
![[8.III.B.Cancer incidence]]
<<tiddler [[8.III.B.Cancer incidence]]>>
![[8.III.C.Cancer-related deaths]]
<<tiddler [[8.III.C.Cancer-related deaths]]>>
![[8.III.D.Cancer and heredity]]
<<tiddler [[8.III.D.Cancer and heredity]]>>
![[8.III.E.Cancer and geography]]
<<tiddler [[8.III.E.Cancer and geography]]>>
![[8.III.F.Acquired preneoplastic disorders (Table 8-2)]]
<<tiddler [[8.III.F.Acquired preneoplastic disorders (Table 8-2)]]>>
![[8.III.G.Prevention modalities in cancer]]
<<tiddler [[8.III.G.Prevention modalities in cancer]]>>
<html><a name="HC008018"></a> <br><a name="P008017"></a><div class="PA" style="color: black; "><ol type="1"> <li>Inherited predisposition to cancer accounts for 5% of all cancers.</li><li>Categories of inherited cancers (<span>[[Table 8-1|Table 8-1. SELECTED INHERITED CANCER SYNDROMES]]</span> and <span>[[Fig. 8-3|Figure 8-3]]</span>)</li><ol type="a"> <li>Autosomal dominant cancer syndromes</li><li>Autosomal recessive disorders involving DNA repair</li><li>Familial cancers</li> </ol> </ol>
</div></html>
<html><a name="HC008019"></a> <br><a name="P008018"></a><div class="PA" style="color: black; "><ol type="1"> <li>Worldwide</li><ul> <li>Malignant melanoma is increasing at the most rapid rate of all cancers.
<blockquote style="color: blue; ">Malignant melanoma: most rapidly increasing cancer</blockquote></li> </ul><li>China</li><ul> <li>Nasopharyngeal carcinoma secondary to Epstein-Barr virus (EBV)</li> </ul><li>Japan</li><ul> <li>Stomach adenocarcinoma due to smoked foods</li> </ul><li>Southeast Asia</li><ul> <li>Hepatocellular carcinoma due to hepatitis B virus plus aflatoxins (produced by <i>Aspergillus</i>) in food</li> </ul><li>Africa</li><ul> <li>Burkitt's lymphoma due to EBV and Kaposi's sarcoma due to human herpesvirus 8</li> </ul> </ol>
</div></html>
<html><a name="HC008020"></a><span>[[Table 8-2|Table 8-2. ACQUIRED PRENEOPLASTIC DISORDERS*]]</span> <br> <br><a name="P008019"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Actinic (solar) keratosis: precursor of squamous cell carcinoma</blockquote>
</div></html>
<html><a name="HC008021"></a> <br><a name="P008020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Lifestyle modifications</li><ol type="a"> <li>Stop smoking cigarettes-the most important factor (refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>)
<blockquote style="color: blue; ">Cessation of smoking is most important factor in decreasing risk for cancer.</blockquote></li><li>Increase fiber/decrease dietary saturated animal fat</li><ul> <li>Decreases risk for colorectal cancer</li> </ul><li>Reduce alcohol intake (refer to <span macro="tag [[06 Environmental Pathology]] [[Chapter 6]]"></span>)</li><li>Reduce weight</li><ul> <li>(1) Increased adipose tissue increases aromatase conversion of androgens to estrogen.</li><li>(2) Increased estrogen increases risk for endometrial and breast cancer.</li> </ul> </ol><li>Immunization</li><ol type="a"> <li>Hepatitis B (HBV) vaccination
<blockquote style="color: blue; ">HBV immunization: ↓ risk for hepatocellular carcinoma</blockquote></li><ul> <li>Immunization decreases the risk for hepatocellular carcinoma due to hepatitis B-induced postnecrotic cirrhosis.</li> </ul><li>Human papillomavirus (HPV) immunization
<blockquote style="color: blue; ">Human papillomavirus immunization: ↓ risk for cervical cancer</blockquote></li><ul> <li>Decreases the risk for developing cervical squamous cancer</li> </ul> </ol><li>Screening procedures</li><ol type="a"> <li>Cervical Papanicolaou (Pap) smears</li><ul> <li>(1) Decreases risk for cervical cancer
<blockquote style="color: blue; ">Cervical cancer is the least common gynecologic cancer in the United States.</blockquote></li><li>(2) Pap smear detects cervical dysplasia, which can be surgically removed.</li><ul> <li>(a) Detection of low-grade dysplasia-sensitivity ∼70%, specificity 75%</li><li>(b) Detection of high-grade dysplasia-sensitivity 75%, specificity 95%
<blockquote style="color: blue; ">Cervical Pap smear: most responsible for ↓ incidence/mortality rate for cervical cancer</blockquote></li> </ul> </ul><li>Colonoscopy</li><ul> <li>Detects and removes polyps that are precancerous</li> </ul><li>Mammography</li><ul> <li>Detects nonpalpable breast masses</li> </ul><li>Prostate-specific antigen (PSA)
<blockquote style="color: blue; ">PSA: more sensitive than specific</blockquote></li><ul> <li>(1) Detects prostate cancer</li><li>(2) Lacks specificity (increased false positive results)</li><ul> <li>PSA may be increased in prostate hyperplasia</li> </ul> </ul> </ol><li>Treatment of conditions that predispose to cancer
<blockquote style="color: blue; ">Rx <i>H. pylori</i> infection: ↓ risk for developing gastric lymphoma/adenocarcinoma</blockquote></li><ol type="a"> <li>Treatment of <i>Helicobacter pylori</i> infections</li><ul> <li>Decreases risk for developing malignant lymphoma and adenocarcinoma of the stomach</li> </ul><li>Treatment of gastroesophageal reflux disease (GERD)
<blockquote style="color: blue; ">Rx GERD: ↓ risk for distal adenocarcinoma of esophagus</blockquote></li><ul> <li>Decreases the risk for developing distal adenocarcinoma arising from Barrett's esophagus</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC008023"></a> <br><a name="P008023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Point mutations are the most common type of mutation.
<blockquote style="color: blue; ">Point mutations: most common type of mutation in cancer</blockquote></li><li>Balanced translocations</li><li>Other mutations</li><ul> <li>Deletion, gene amplification (multiple copies of a gene), overexpression (increase in baseline gene activity)</li> </ul> </ol>
</div></html>
<html><a name="HC008024"></a> <br><a name="P008024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Proto-oncogenes
<blockquote style="color: blue; ">Proto-oncogenes: involved in normal growth and repair</blockquote></li><ol type="a"> <li>Involved in normal growth and repair</li><li>Functions of proto-oncogene protein products</li><ul> <li>Growth factors, growth factor receptors, signal transducers, nuclear transcribers</li> </ul><li>Mutations cause sustained activity of the genes (<span>[[Table 8-3|Table 8-3. SOME PROTO-ONCOGENES AND THEIR FUNCTIONS, MUTATIONS, AND ASSOCIATED CANCERS]]</span>)</li> </ol><li>Suppressor genes (anti-oncogenes)
<blockquote style="color: blue; ">Suppressor genes: protect against unregulated cell growth</blockquote></li><ol type="a"> <li>Protect against unregulated cell growth</li><li>Control G<sub>1</sub> to S phase of the cell cycle and nuclear transcription</li><li>Mutations cause unregulated cell proliferation (<span>[[Table 8-4|Table 8-4. SOME TUMOR SUPPRESSOR GENES, THEIR FUNCTIONS, AND ASSOCIATED CANCERS]]</span>).</li> </ol><li>Antiapoptosis genes; <i>BCL2</i> family of genes
<blockquote style="color: blue; "><i>BCL2</i> gene family: antiapoptosis genes</blockquote></li><ol type="a"> <li>Protein products prevent cytochrome <i>c</i> from leaving mitochondria.</li><ul> <li>Cytochrome <i>c</i> in the cytosol activates caspases initiating apoptosis.</li> </ul><li>Mutation causes increased gene activity (e.g., overexpression), which prevents apoptosis; e.g., B-cell follicular lymphoma.</li><ul> <li>(1) <i>BCL2</i> gene family (chromosome 18) produces gene products that prevent mitochondrial leakage of cytochrome <i>c</i> (signal for apoptosis).</li><li>(2) Translocation t(14;18) causes overexpression of the BCL2 protein product.</li><ul> <li>Prevents apoptosis of B lymphocytes causing B-cell follicular lymphoma</li> </ul> </ul> </ol><li>Apoptosis genes</li><ol type="a"> <li>Regulate programmed cell death</li><li>Example-<i>BAX</i> apoptosis gene
<blockquote style="color: blue; "><i>BAX</i> gene: apoptosis gene</blockquote></li><ul> <li>(1) Activated by a <i>TP53</i> suppressor gene product if DNA damage is excessive</li><li>(2) BAX protein product inactivates the <i>BCL2</i> antiapoptosis gene.</li><li>(3) Mutation inactivating <i>TP53</i> suppressor gene renders the <i>BAX</i> gene inoperative, which prevents apoptosis.</li> </ul> </ol><li>DNA repair genes (see <span>[[Tables 8-1|Table 8-1. SELECTED INHERITED CANCER SYNDROMES]]</span> and <span>[[8-4|Table 8-4. SOME TUMOR SUPPRESSOR GENES, THEIR FUNCTIONS, AND ASSOCIATED CANCERS]]</span>)
<blockquote style="color: blue; ">Repair genes: correct errors in nucleotide pairing; excise pyrimidine dimers</blockquote></li><ol type="a"> <li>Examples of DNA repair</li><ul> <li>(1) Mismatch repair genes produce proteins that correct errors in nucleotide pairing.</li><li>(2) Nucleotide excision repair pathway excises pyrimidine dimers in ultraviolet light (UV)-damaged skin (<span>[[Fig. 8-4|Figure 8-4]]</span>).
<blockquote style="color: blue; ">Enzymes involved in dimer excision: endonuclease, exonuclease, ligase</blockquote></li> </ul><li>Effect of mutations involving DNA repair genes</li><ul> <li>Allows cells with nonlethal damage to proliferate, which increases the risk for cancer</li> </ul> </ol> </ol>
</div></html>
![[8.IV.A.Types of gene mutations]]
<<tiddler [[8.IV.A.Types of gene mutations]]>>
![[8.IV.B.Genes involved in cancer]]
<<tiddler [[8.IV.B.Genes involved in cancer]]>>
<html><a name="HC008026"></a><span>[[Table 8-5|Table 8-5. CHEMICAL CARCINOGENS]]</span> <br> <br><a name="P008025"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Tobacco is the agent most responsible for cancer and cancer deaths in the United States.</blockquote>
<ol type="1"> <li>Polycyclic hydrocarbons in tobacco smoke</li><ul> <li>Most common group of carcinogens in the United States</li> </ul><li>Mechanisms</li><ol type="a"> <li>Direct-acting carcinogens</li><ul> <li>Contain electron-deficient atoms that react with electron-rich atoms in DNA (e.g., alkylating agents)</li> </ul><li>Indirect-acting carcinogens</li><ul> <li>Activated by the liver cytochrome P-450 system (e.g., polycyclic hydrocarbons)</li> </ul> </ol><li>Sequence of chemical carcinogenesis
<blockquote style="color: blue; ">Chemical carcinogenesis: initiation → promotion → progression</blockquote></li><ol type="a"> <li>Initiation</li><ul> <li>Irreversible mutation</li> </ul><li>Promotion</li><ul> <li>Promoters (e.g., estrogen) stimulate mutated cells to enter the cell cycle.</li> </ul><li>Progression</li><ul> <li>(1) Development of tumor heterogeneity</li><li>(2) Examples-production of cells that invade or metastasize</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC008027"></a> <br><a name="P008026"></a><div class="PA" style="color: black; "><ol type="1"> <li>Viruses (<span>[[Table 8-6|Table 8-6. ONCOGENIC RNA AND DNA VIRUSES]]</span>)</li><li>Bacteria</li><ul> <li>Examples-stomach cancer and low-grade malignant lymphoma due to <i>Helicobacter pylori</i></li> </ul><li>Parasites</li><ol type="a"> <li><i>Schistosoma hematobium</i></li><ul> <li>Squamous cell carcinoma of the urinary bladder</li> </ul><li><i>Clonorchis sinensis</i> and <i>Opisthorchis viverrini</i>
<blockquote style="color: blue; ">Pathogens and cancer: viruses > bacteria > parasites</blockquote></li><ul> <li>Cholangiocarcinoma of the bile ducts</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC008028"></a> <br><a name="P008027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Ionizing radiation-induced cancers</li><ol type="a"> <li>Mechanism</li><ul> <li>Hydroxyl free radical injury to DNA</li> </ul><li>Examples
<blockquote style="color: blue; ">Leukemia: most common cancer due to ionizing radiation</blockquote></li><ul> <li>(1) Acute myelogenous or chronic myelogenous leukemia</li><ul> <li>Increased risk of leukemia in radiologists and individuals exposed to radiation in nuclear reactors</li> </ul><li>(2) Papillary thyroid carcinoma</li><li>(3) Lung, breast, and bone cancers</li><li>(4) Liver angiosarcoma</li><ul> <li>Due to radioactive thorium dioxide used to visualize the arterial tree</li> </ul> </ul> </ol><li>UV light-induced cancers</li><ol type="a"> <li>Mechanism
<blockquote style="color: blue; ">Basal cell carcinoma: most common cancer due to excessive UV light exposure</blockquote></li><ul> <li>Formation of pyrimidine dimers, which distort DNA (see <span>[[Fig. 8-4|Figure 8-4]]</span>)</li> </ul><li>Basal cell carcinoma (see <span>[[Fig. 24-7B|Figure 24-7]]</span>), squamous cell carcinoma (see <span>[[Fig. 24-7D|Figure 24-7]]</span>), malignant melanoma (see <span>[[Fig. 24-5H|Figure 24-5]]</span>)</li> </ol> </ol>
</div></html>
![[8.V.A.Chemical carcinogens (Table 8-5)]]
<<tiddler [[8.V.A.Chemical carcinogens (Table 8-5)]]>>
![[8.V.B.Microbes]]
<<tiddler [[8.V.B.Microbes]]>>
![[8.V.C.Radiation]]
<<tiddler [[8.V.C.Radiation]]>>
![[8.V.D.Physical injury]]
<<tiddler [[8.V.D.Physical injury]]>>
<html><a name="HC008029"></a> <br><a name="P008028"></a><div class="PA" style="color: black; "><ol type="1"> <li>Squamous cell carcinoma may develop in third-degree burn scars.</li><li>Squamous cell carcinoma may develop at the orifices of chronically draining sinuses (e.g., chronic osteomyelitis).</li> </ol>
</div></html>
<html><a name="HC008031"></a> <br><a name="P008030"></a><div class="PA" style="color: black; "><ol type="1"> <li>Humoral immunity</li><ul> <li>Involves antibodies and complement</li> </ul><li>Type IV cellular immunity</li><ol type="a"> <li>Efficient mechanism for killing cancer cells
<blockquote style="color: blue; ">Cytotoxic CD8 T cells: most effective host defense against cancer</blockquote></li><li>Cytotoxic CD8 T cells</li><ul> <li>Recognize altered class I antigens on neoplastic cells and destroy them</li> </ul> </ol><li>Natural killer cells</li><ul> <li>Direct killing and indirect killing through type II hypersensitivity</li> </ul><li>Macrophages</li><ul> <li>Activated by γ-interferon</li> </ul> </ol>
</div></html>
<html><a name="HC008032"></a> <br><a name="P008031"></a><div class="PA" style="color: black; "><ol type="1"> <li>Grading criteria</li><ol type="a"> <li>Degree of differentiation (e.g., low, intermediate, or high grade)</li><li>Nuclear features, invasiveness</li> </ol><li>Staging criteria
<blockquote style="color: blue; ">↓ Prognosis: M > N > T</blockquote></li><ol type="a"> <li>Most important prognostic factor</li><li>TNM system</li><ul> <li>(1) Progresses from the least to the most important prognostic factor</li><li>(2) T refers to tumor size.</li><ul> <li>≥ 2 cm correlates with metastatic ability.</li> </ul><li>(3) N refers to whether lymph nodes are involved.</li><li>(4) M refers to extranodal metastases (e.g., liver, lung).</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC008033"></a> <br><a name="P008032"></a><div class="PA" style="color: black; "><ol type="1"> <li>Cachexia (wasting disease)</li><ol type="a"> <li>Generalized catabolic reaction</li><ul> <li>Anorexia, muscle wasting, loss of subcutaneous fat, fatigue
<blockquote style="color: blue; ">Cachexia: TNF-α pivotal role</blockquote></li> </ul><li>Mechanism</li><ul> <li>(1) Chronic low levels of tumor necrosis factor-α (called cachectin)</li><li>(2) Secreted from host macrophages and cancer cells</li><li>(3) Suppresses appetite center in hypothalamus</li><li>(4) Stimulus for apoptosis of cells</li> </ul> </ol><li>Anemia</li><ol type="a"> <li>Anemia of chronic disease
<blockquote style="color: blue; ">Anemia of chronic disease: most common anemia in cancer</blockquote></li><li>Iron deficiency</li><ul> <li>Due to gastrointestinal blood loss (e.g., colorectal cancer)</li> </ul><li>Macrocytic anemia</li><ul> <li>Due to folate deficiency from rapid tumor growth</li> </ul><li>Myelophthisic anemia</li><ul> <li>(1) Anemia related to metastasis to bone</li><li>(2) Immature hematopoietic elements in peripheral blood (i.e., leukoerythroblastic smear) (see <span>[[Fig. 12-1|Figure 12-1]]</span>)</li><ul> <li>(a) Nucleated red blood cells, immature neutrophils (e.g., myeloblasts, metamyelocytes) in peripheral blood</li><li>(b) Tear drop red blood cells indicate myelofibrosis secondary to bone metastasis</li> </ul> </ul> </ol><li>Hemostasis abnormalities
<blockquote style="color: blue; ">Hemostasis: thrombogenic</blockquote></li><ol type="a"> <li>Increased risk for vessel thrombosis</li><ul> <li>(1) Due to thrombocytosis, increased synthesis of coagulation factors (e.g., fibrinogen, factors V and VIII)
<blockquote style="color: blue; ">Gram-negative sepsis: most common cause of death in cancer</blockquote></li><li>(2) Release of procoagulants from cancer cells (e.g., pancreatic carcinoma)</li> </ul><li>Disseminated intravascular coagulation</li><ul> <li>Due to release of tissue thromboplastin from cancer cells</li> </ul> </ol><li>Fever
<blockquote style="color: blue; ">Hypercalcemia: most common paraneoplastic syndrome</blockquote></li><ol type="a"> <li>Usually due to infection</li><li>Example-gram-negative sepsis from <i>Escherichia coli</i> or <i>Pseudomonas aeruginosa</i></li> </ol><li>Paraneoplastic syndromes
<blockquote style="color: blue; ">Acanthosis nigricans: may be associated with stomach cancer</blockquote></li><ol type="a"> <li>Distant effects of a tumor that are unrelated to metastasis</li><ul> <li>May predate the onset of metastasis</li> </ul><li>Occur in 10% to 15% of cancer patients
<blockquote style="color: blue; ">Signs of ectopic hormone production: hypercalcemia, hyponatremia, hypercortisolism, polycythemia</blockquote></li><li>Involve multiple organ systems and mimic metastatic disease (<span>[[Table 8-7|Table 8-9. TUMOR MARKERS AND ASSOCIATED CANCERS]]</span>; <span>[[Fig. 8-5|Figure 8-5]]</span>)</li><li>May involve ectopic secretion of hormone (<span>[[Table 8-8|Table 8-8. PARANEOPLASTIC SYNDROME ENDOCRINOPATHIES]]</span>)</li> </ol> </ol>
</div></html>
![[8.VI.A.Host defense against cancer]]
<<tiddler [[8.VI.A.Host defense against cancer]]>>
![[8.VI.B.Grading and staging of cancer]]
<<tiddler [[8.VI.B.Grading and staging of cancer]]>>
![[8.VI.C.Cancer effects on the host]]
<<tiddler [[8.VI.C.Cancer effects on the host]]>>
![[8.VI.D.Tumor markers (biomarkers)]]
<<tiddler [[8.VI.D.Tumor markers (biomarkers)]]>>
<html><a name="HC008034"></a> <br><a name="P008033"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Hormone tumor marker: calcitonin (medullary carcinoma of thyroid)</blockquote>
<ol type="1"> <li>Biologic markers (<span>[[Table 8-9|Table 8-9. TUMOR MARKERS AND ASSOCIATED CANCERS]]</span>)</li><ul> <li>Include hormones, enzymes, oncofetal antigens, glycoproteins</li> </ul><li>Identify tumors</li><li>Estimate tumor burden</li><li>Detect recurrence</li><li>Indicator of tumor response to treatment</li> </ol>
</div></html>
<html><a name="HC009002"></a> <br><a name="PB009001"></a><div class="BB" style="color: rgb(47, 79, 79); ">The intensity of <b>treatment to lower cholesterol</b> is directly related to the degree of risk for CHD. The LDL cholesterol goal < 100 mg/dL (some studies suggest <70 mg/dL) if the patient has known coronary heart disease, which invariably requires the use of hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitors. For persons without CHD, the LDL cholesterol goal is subdivided into those with a 0-1 risk factor (goal < 160 mg/dL) or those with multiple (2+) risk factors (goal < 130 mg/dL). The risk factors include age (male ≥ 45 years, female ≥ 55 years); family history of premature CHD (e.g., family member with myocardial infarction before 55 years of age); LDL > 160 mg/dL; current cigarette smoking; blood pressure ≥ 140/90 mg/dL (or on antihypertensive medicine); and HDL < 40 mg/dL (if ≥60 mg/dL, subtract 1).</div><a name="P009001"></a><div class="PA" style="color: black; "><ol type="1"> <li>Chylomicron (<span>[[Fig. 9-1A|Figure 9-1]]</span>)</li><ol type="a"> <li>Transports diet-derived triglyceride (TG) in the blood</li><li>Composition</li><ul> <li>(1) Protein (2%)</li><li>(2) TG (87%)</li><li>(3) Cholesterol (CH; 3%)</li><li>(4) Phospholipid (8%)
<blockquote style="color: blue; ">Chylomicron: diet-derived triglyceride</blockquote></li> </ul><li>Synthesized in intestinal epithelium</li><ul> <li>(1) Requires apolipoprotein (apo) B-48 for assembly and secretion</li><li>(2) Nascent chylomicrons in the circulation obtain apo CII and apo E from high density lipoprotein (HDL)</li> </ul><li>Absent during fasting
<blockquote style="color: blue; ">Chylomicrons: absent during fasting</blockquote></li><li>If increased, it forms a creamy supranate.</li><ul> <li>(1) Test tube must be left upright in a refrigerator overnight.
<blockquote style="color: blue; ">Chylomicrons: turbid supranate</blockquote></li><li>(2) Chylomicron floats on top of plasma because it has very little protein (low density).</li> </ul><li>Source of fatty acids and glycerol</li><ul> <li>Used to synthesize TG in the liver and adipose</li> </ul><li>Hydrolysis by capillary lipoprotein lipase (CPL) leaves a chylomicron remnant.</li><ul> <li>Chylomicron remnants are removed by apo E receptors in the liver.</li> </ul> </ol><li>Very low density lipoprotein (VLDL) (<span>[[Fig. 9-1B|Figure 9-1]]</span>)
<blockquote style="color: blue; ">VLDL: liver-derived triglyceride</blockquote></li><ol type="a"> <li>Transports liver-synthesized TG in the blood</li><ul> <li>Requires apolipoprotein B-100 for assembly and secretion</li> </ul><li>Composition</li><ul> <li>(1) Protein (9%)</li><li>(2) TG (55%)</li><li>(3) CH (17%)</li><li>(4) Phospholipid (19%)</li> </ul><li>Source of fatty acids and glycerol</li><ul> <li>(1) Used to synthesize TG in the adipose tissue
<blockquote style="color: blue; ">Hypertriglyceridemia: causes turbidity in plasma</blockquote></li><li>(2) Hydrolysis by CPL produces intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL).
<blockquote style="color: blue; ">VLDL → IDL → LDL</blockquote></li><li>(3) Some of the IDL is removed from blood by apo E receptors in the liver.</li> </ul><li>Cholesterol ester transport protein (CETP)</li><ul> <li>(1) Transfers CH from HDL to VLDL</li><li>(2) Transfers TG from VLDL to HDL</li><li>(3) An increase in VLDL always causes a decrease in HDL-CH.</li> </ul><li>If increased, it forms a creamy infranate.</li><ul> <li>Note that the protein is greater in VLDL than in chylomicrons, so it sinks rather than floats in plasma.</li> </ul><li>TG levels</li><ul> <li>(1) Optimal level < 150 mg/dL</li><li>(2) Borderline high level 150 to 199 mg/dL</li><li>(3) High level 200 to 499 mg/dL</li><li>(4) Very high level > 500 mg/dL</li> </ul> </ol><li>Low-density lipoprotein (LDL) (see <span>[[Fig. 9-1B|Figure 9-1]]</span>)</li><ol type="a"> <li>Transports cholesterol in the blood</li><li>Derives from continued hydrolysis of IDL by CPL</li><li>Removed from blood by LDL receptors in peripheral tissue
<blockquote style="color: blue; ">LDL: transports cholesterol</blockquote></li><li>Composition</li><ul> <li>(1) Protein (22%)</li><li>(2) TG (10%)</li><li>(3) CH (47%)</li><li>(4) Phospholipid (21%)</li> </ul><li>Calculated LDL = CH - HDL - TG/5
<blockquote style="color: blue; ">LDL = CH - HDL - TG/5</blockquote></li><ul> <li>(1) Presence of chylomicrons falsely lowers calculated LDL by increasing diet-derived triglyceride; hence, fasting is required for an accurate calculated LDL.</li><li>(2) To reduce the chance for a falsely low calculated LDL, LDL is directly measured if the serum TG > 400 mg/dL.</li> </ul><li>Functions of cholesterol</li><ul> <li>(1) Component of the cell membrane</li><li>(2) Synthesis of vitamin D, adrenal cortex hormones, bile salts and acids</li> </ul><li>Ranges of LDL</li><ul> <li>(1) Optimal level < 100 mg/dL.</li><ul> <li>Risk for coronary heart disease (CHD) markedly reduced</li> </ul><li>(2) Near optimal level is 100 to 129 mg/dL.</li><li>(3) Borderline high level is 130 to 159 mg/dL.</li><li>(4) High level is 160 to 189 mg/dL.</li><li>(5) Very high level > 190 mg/dL.</li><ul> <li>Greatest risk for CHD</li> </ul> </ul><li>Fasting is <i>not</i> required for an accurate serum CH.
<blockquote style="color: blue; ">Serum CH: fasting not required</blockquote></li><ul> <li>Note that the CH content in chylomicrons is <3%; hence, fasting does <i>not</i> have a medically significant effect on the serum level.</li> </ul> </ol><li>High-density lipoprotein (HDL) (see <span>[[Fig. 9-1B|Figure 9-1]]</span>)
<blockquote style="color: blue; ">HDL: "good CH"</blockquote></li><ol type="a"> <li>"Good cholesterol"</li><ul> <li>Increased by exercise, wine, estrogen</li> </ul><li>Composition</li><ul> <li>(1) Protein (50%)</li><li>(2) TG (3%; unless VLDL is increased)</li><li>(3) CH (20%)</li><li>(4) Phospholipid (27%)</li> </ul><li>Synthesized by the liver and small intestine</li><li>Functions of HDL
<blockquote style="color: blue; ">HDL: source of apolipoproteins</blockquote></li><ul> <li>(1) Source of apolipoproteins for other lipoprotein fractions</li><li>(2) Removes cholesterol from atherosclerotic plaques
<blockquote style="color: blue; ">HDL: removes cholesterol from plaques for disposal in the liver</blockquote></li><ul> <li>(a) Delivers CH from peripheral tissue to the liver</li><li>(b) CH is either excreted into bile or converted into bile acids/salts.</li> </ul> </ul><li>Measured in the laboratory as HDL-CH</li><ul> <li>(1) Inverse association of levels of HDL-CH and incidence and prevalence of CHD</li><li>(2) Decreased if VLDL is increased (see earlier)</li><li>(3) Ranges of HDL-CH</li><ul> <li>(a) High level (optimal) ≥60 g/dL</li><li>(b) Low level (suboptimal) < 40 mg/dL</li> </ul><li>(4) Fasting is <i>not</i> required for an accurate serum HDL-CH.</li><ul> <li>Same reason as for serum CH.
<blockquote style="color: blue; ">↑ VLDL causes ↓ HDL</blockquote></li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC009003"></a> <br><a name="PB009002"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Nonpharmacologic treatment</b> includes dietary modification, increasing activity with aerobic exercises, and cessation of smoking. Dietary modification consists of a low CH, low fat diet (fat intake < 30% of total caloric intake); polyunsaturated fat up to 10% of total calories; monounsaturated fat up to 20% of total calories; saturated fat < 7% of total calories; no more than 200 mg/day of CH; and dietary fiber 20 to 30 g/day. Pharmacologic treatment consists of the use of HMG-CoA reductase inhibitors ("statins"; most effective); nicotinic acid (least expensive lipid-lowering agent; also decreases TG, and increases HDL greater than other drugs); bile salt sequestrants; and cholesterol absorption inhibitors.</div><a name="PB009003"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Nonpharmacologic treatment</b> is to reduce alcohol intake and carbohydrate intake. Increase intake of omega-3 fatty acids from fish, flaxseed oil, or other sources (up to 3 g/day). <b>Pharmacologic therapy</b> consists of nicotinic acid or fibric acid derivatives.</div><a name="P009002"></a><div class="PA" style="color: black; "><ol type="1"> <li>Type I hyperlipoproteinemia</li><ol type="a"> <li>Epidemiology</li><ul> <li>(1) Autosomal recessive</li><li>(2) Rare childhood disease</li> </ul><li>Pathogenesis (see <span>[[Fig. 9-1A and B|Figure 9-1]]</span>)
<blockquote style="color: blue; ">Type I: ↓ CPL or ↓ apo CII</blockquote></li><ul> <li>(1) Deficiency of CPL <i>or</i></li><li>(2) Deficiency of apo CII</li> </ul><li>Clinical findings</li><ul> <li>(1) Chylomicrons are primarily increased in early childhood.</li><li>(2) VLDL increases later in life.</li><li>(3) Presents with acute pancreatitis</li><ul> <li>Pancreatic vessels filled with chylomicrons rupture.</li> </ul> </ul><li>Laboratory findings</li><ul> <li>(1) Increase in serum TG > 1000 mg/dL (primarily chylomicrons)</li><li>(2) Turbid supranate (chylomicrons) and clear infranate (early childhood)</li><li>(3) Normal (usual case) to moderately increased serum CH</li> </ul> </ol><li>Type II hyperlipoproteinemia</li><ol type="a"> <li>Laboratory findings</li><ul> <li>(1) Serum LDL > 190 mg/dL</li><li>(2) Serum CH > 260 mg/dL</li><ul> <li>(a) Serum TG < 300 mg/dL (called type IIa)</li><li>(b) Serum TG > 300 mg/dL (called type IIb)</li> </ul> </ul><li>Pathogenesis</li><ul> <li>Decreased synthesis of LDL receptors (see <span>[[Fig. 9-1B|Figure 9-1]]</span>)
<blockquote style="color: blue; ">Type II hyperlipoproteinemia: ↑ LDL due to ↓ LDL receptors</blockquote></li> </ul><li>Acquired causes of hypercholesterolemia</li><ul> <li>(1) Primary hypothyroidism</li><ul> <li>Decrease in LDL receptor synthesis or function</li> </ul><li>(2) Nephrotic syndrome</li><ul> <li>Increase in LDL correlates with the degree of hypoalbuminemia</li> </ul><li>(3) Extrahepatic cholestasis (obstruction of bile)</li><ul> <li>Bile contains CH for excretion</li> </ul> </ul><li>Familial hypercholesterolemia</li><ul> <li>(1) Autosomal dominant (AD) disorder</li><li>(2) Deficiency of LDL receptors</li><li>(3) Clinical findings</li><ul> <li>(a) Premature coronary artery disease and stroke</li><li>(b) Tendon xanthomas (<span>[[Fig. 9-2A|Figure 9-2]]</span>)
<blockquote style="color: blue; ">Achilles tendon xanthoma: pathognomonic for familial hypercholesterolemia</blockquote></li><ul> <li>Cholesterol deposit located over tendons (e.g., Achilles) and extensor surfaces of joints</li> </ul><li>(c) Xanthelasma (<span>[[Fig. 9-2B|Figure 9-2]]</span>)</li><ul> <li>Yellow, raised plaque on the eyelid</li> </ul> </ul> </ul><li>Polygenic hypercholesterolemia (type IIa)</li><ul> <li>(1) Most common hereditary cause (85% of cases)</li><li>(2) Multifactorial (polygenic) inheritance</li><li>(3) Alteration in regulation of LDL levels</li><li>(4) Normal serum TG</li> </ul><li>Familial combined hypercholesterolemia (type IIb)</li><ul> <li>(1) AD inheritance.</li><li>(2) Serum CH and TG begin to increase around puberty.</li><li>(3) Associated with metabolic syndrome (refer to <span macro="tag [[22 Endocrine Disorders]] [[Chapter 22]]"></span>)</li><li>(4) Increase in CH and TG and decrease in HDL</li> </ul> </ol><li>Type III hyperlipoproteinemia</li><ol type="a"> <li>Laboratory findings</li><ul> <li>(1) Serum CH and TG > 300 mg/dL</li><li>(2) Serum CH 250 to 500 mg/dL</li><li>(3) LDL < 190 mg/dL</li> </ul><li>Familial dysbetalipoproteinemia ("remnant disease")
<blockquote style="color: blue; ">Type III hyperlipoproteinemia: deficiency apo E; ↑ remnants</blockquote></li><ul> <li>(1) AD inheritance</li><li>(2) Deficiency of apo E (see <span>[[Fig. 9-1B|Figure 9-1]]</span>)</li><li>(3) Decreased liver uptake of chylomicron remnants and IDL</li> </ul><li>Clinical findings</li><ul> <li>(1) Palmar xanthomas in flexor creases (<span>[[Fig. 9-2C|Figure 9-2]]</span>)
<blockquote style="color: blue; ">Type III: palmar xanthomas</blockquote></li><li>(2) Increased risk for coronary artery disease</li><li>(3) Increased risk for peripheral vascular disease (unlike type II disorders)</li> </ul><li>Laboratory findings</li><ul> <li>(1) Serum CH and TG > 300 mg/dL</li><li>(2) Serum CH 250 to 500 mg/dL</li><li>(3) LDL < 190 mg/dL</li><li>(4) Confirm diagnosis with ultracentrifugation to identify remnants</li><ul> <li>Lipoprotein electrophoresis and identification of apo E gene defect are other studies that can be used.</li> </ul> </ul><li>Treatment</li><ul> <li>Fibric acid derivatives</li> </ul> </ol><li>Type IV hyperlipoproteinemia</li><ol type="a"> <li>Laboratory findings</li><ul> <li>(1) Serum TG > 300 mg/dL</li><li>(2) Serum CH 250 to 500 mg/dL</li><li>(3) Serum LDL < 190 mg/dL</li><li>(4) Turbid infranate after refrigeration</li> </ul><li>Increase in VLDL
<blockquote style="color: blue; ">Type IV hyperlipoproteinemia: ↑ VLDL; most common lipid disorder</blockquote></li><ul> <li>Due to increase in synthesis or decrease in catabolism (see <span>[[Fig. 9-1B|Figure 9-1]]</span>)</li> </ul><li>Acquired causes of hypertriglyceridemia</li><ul> <li>(1) Excess alcohol intake
<blockquote style="color: blue; ">Type IV hyperlipoproteinemia: most common cause is alcohol excess</blockquote></li><li>(2) Oral contraceptives</li><ul> <li>Estrogen increases synthesis of VLDL</li> </ul><li>(3) Diabetes mellitus</li><ul> <li>Decreased muscle and adipose CLP</li> </ul><li>(4) Chronic renal failure</li><ul> <li>Increased synthesis of VLDL</li> </ul><li>(5) Thiazides, β-blockers</li><ul> <li>Possible inhibition of CPL</li> </ul> </ul><li>Familial hypertriglyceridemia</li><ul> <li>(1) Autosomal dominant disorder</li><li>(2) Clinical findings</li><ul> <li>(a) Eruptive xanthomas (<span>[[Fig. 9-2D|Figure 9-2]]</span>)
<blockquote style="color: blue; ">Type IV: eruptive xanthomas</blockquote></li><ul> <li>Yellow, papular lesions</li> </ul><li>(b) Increased risk for coronary artery and peripheral vascular disease</li> </ul> </ul> </ol><li>Type V hyperlipoproteinemia
<blockquote style="color: blue; ">Type IV Rx: ↓ carbohydrate and alcohol intake</blockquote></li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Increase in chylomicrons and VLDL</li><li>(2) Due to decreased activation and release of CPL (see <span>[[Fig. 9-1A and B|Figure 9-1]]</span>)</li> </ul><li>Familial hypercholesterolemia (type IV) + exacerbating disorder</li><ul> <li>Exacerbating disorders-diabetic ketoacidosis (DKA; most common), alcohol</li> </ul><li>Increased serum TG > 1000 mg/dL; normal CH and LDL</li><li>Turbid plasma
<blockquote style="color: blue; ">Type V hyperlipoproteinemia: ↑ VLDL + chylomicrons</blockquote></li><ul> <li>(1) Supranate after refrigeration, due to increased chylomicrons</li><li>(2) Infranate after refrigeration, due to increased VLDL</li> </ul><li>Hyperchylomicronemia syndrome
<blockquote style="color: blue; ">Type V: hyperchylo-micronemia syndrome</blockquote></li><ul> <li>(1) Eruptive xanthomas</li><li>(2) Increased incidence of acute pancreatitis</li><li>(3) Lipemia retinalis</li><ul> <li>Retinal vessels look like milk; blurry vision</li> </ul><li>(4) Dyspnea and hypoxemia</li><ul> <li>Impaired gas exchange in pulmonary capillaries</li> </ul><li>(5) Hepatosplenomegaly</li><li>(6) Increase in serum TG (usually >1000 mg/dL)</li><li>(7) Normal serum CH and LDL</li><li>(8) Turbid supranate and infranate after refrigeration</li> </ul><li>Treatment</li><ul> <li>(1) Treat exacerbating disorder (e.g., DKA)</li><li>(2) Nicotinic acid or fibric acid derivatives</li> </ul> </ol><li>Apolipoprotein B deficiency (abetalipoproteinemia)</li><ol type="a"> <li>Autosomal recessive</li><li>Deficiency of apolipoprotein B-48 and B-100
<blockquote style="color: blue; ">Apo B deficiency: ↓ chylomicrons, VLDL, LDL</blockquote></li><ul> <li>(1) Deficiency of chylomicrons, VLDL, and LDL</li><li>(2) Decrease in serum CH and TG</li> </ul><li>Clinical findings</li><ul> <li>(1) Malabsorption</li><ul> <li>(a) Chylomicrons accumulate in villi and prevent reabsorption of micelles.</li><li>(b) Marked decrease in vitamin E</li> </ul><li>(2) Ataxia (spinocerebellar degeneration), hemolytic anemia with thorny RBCs (acanthocytes) related to vitamin E deficiency.</li> </ul><li>Treatment</li><ul> <li>Vitamin E</li> </ul> </ol> </ol>
</div></html>
![[9.I.A.Lipoprotein fractions]]
<<tiddler [[9.I.A.Lipoprotein fractions]]>>
![[9.I.B.Lipoprotein disorders]]
<<tiddler [[9.I.B.Lipoprotein disorders]]>>
<html><a name="HC009005"></a> <br><a name="P009006"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Medial calcification: dystrophic calcification in muscular arteries</blockquote>
<ol type="1"> <li>Dystrophic calcification in the wall of muscular arteries</li><ul> <li>Examples-calcification in uterine and radial arteries</li> </ul><li>No clinical consequence unless associated with atherosclerosis</li> </ol>
</div></html>
![[9.II.A.Medial calcification]]
<<tiddler [[9.II.A.Medial calcification]]>>
![[9.II.B.Atherosclerosis]]
<<tiddler [[9.II.B.Atherosclerosis]]>>
![[9.II.C.Arteriolosclerosis]]
<<tiddler [[9.II.C.Arteriolosclerosis]]>>
<html><a name="HC009006"></a> <br><a name="PB009004"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Serum C-reactive peptide</b> (CRP) is increased in patients with disrupted (inflammatory) plaques. Plaques may rupture and produce vessel thrombosis, which leads to acute myocardial infarction (MI). CRP may be a stronger predictor of cardiovascular events than LDL.</div><a name="P009007"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Atherosclerosis: endothelial cell injury; platelets/macrophages pivotal roles</blockquote>
<ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Endothelial cell damage of muscular and elastic arteries</li><li>Causes of endothelial cell injury</li><ul> <li>Hypertension, smoking tobacco, homocysteine, LDL</li> </ul><li>Cell response to endothelial injury</li><ul> <li>(1) Macrophages and platelets adhere to damaged endothelium.</li><li>(2) Released cytokines cause hyperplasia of medial smooth muscle cells.</li><li>(3) Smooth muscle cells migrate to the tunica intima.</li><li>(4) Cholesterol enters smooth muscle cells and macrophages (called foam cells).</li><li>(5) Smooth muscle cells release cytokines that produce extracellular matrix.</li><ul> <li>Matrix components include collagen, proteoglycans, and elastin.</li> </ul> </ul><li>Development of fibrous cap (plaque)
<blockquote style="color: blue; ">Fibrous cap: pathognomonic lesion of atherosclerosis</blockquote></li><ul> <li>(1) Components of fibrous cap</li><ul> <li>Smooth muscle, foam cells, inflammatory cells, extracellular matrix</li> </ul><li>(2) Fibrous cap overlies a necrotic center.</li><ul> <li>Cellular debris, cholesterol crystals (slit-like spaces), foam cells</li> </ul><li>(3) Disrupted plaques may extrude underlying necrotic material leading to vessel thrombosis (see <span>[[Fig. 4-13|Figure 4-13]]</span>).
<blockquote style="color: blue; ">C-reactive protein: excellent marker of disrupted fibrous plaques</blockquote></li><li>(4) Fibrous plaque becomes dystrophically calcified and ulcerated.</li> </ul> </ol><li>Sites for atherosclerosis (descending order)
<blockquote style="color: blue; ">Abdominal aorta: most common site for atherosclerosis; no vasa vasorum</blockquote></li><ol type="a"> <li>Abdominal aorta</li><li>Coronary artery</li><li>Popliteal artery</li><li>Internal carotid artery</li> </ol><li>Complications of atherosclerosis</li><ol type="a"> <li>Vessel weakness (e.g., abdominal aortic aneurysm)</li><li>Vessel thrombosis</li><ul> <li>(1) Acute MI (coronary artery)</li><li>(2) Stroke (internal carotid artery, middle cerebral artery)</li><li>(3) Small bowel infarction (superior mesenteric artery)</li> </ul><li>Hypertension</li><ul> <li>Renal artery atherosclerosis may activate the renin-angiotensin-aldosterone system.</li> </ul><li>Peripheral vascular disease</li><ul> <li>(1) Increased risk of gangrene</li><li>(2) Pain in the buttocks and when walking (claudication)</li> </ul><li>Cerebral atrophy</li><ul> <li>Atherosclerosis may involve circle of Willis vessels or internal carotid artery.
<blockquote style="color: blue; ">Complications of atherosclerosis: aneurysms, thrombosis, ischemia</blockquote></li> </ul> </ol> </ol>
</div></html>
<html><a name="HC009007"></a> <br><a name="P009008"></a><div class="PA" style="color: black; "><ul> <li>Hardening of arterioles</li><ol type="1"> <li>Hyaline arteriolosclerosis</li><ol type="a"> <li>Pathogenesis</li><ul> <li>Increased protein is deposited in the vessel wall and occludes the lumen (<span>[[Fig. 9-3|Figure 9-3]]</span>).</li> </ul><li>Associated conditions</li><ul> <li>(1) Diabetes mellitus</li><ul> <li>(a) Due to nonenzymatic glycosylation of proteins in the basement membrane</li><li>(b) Basement membrane leaks protein into the vessel wall.</li> </ul><li>(2) Hypertension</li><ul> <li>Increased intraluminal pressure pushes plasma proteins into the vessel wall.
<blockquote style="color: blue; ">Hyaline arteriolosclerosis: diabetes mellitus, hypertension</blockquote></li> </ul> </ul> </ol><li>Hyperplastic arteriolosclerosis</li><ol type="a"> <li>Pathogenesis</li><ul> <li>(1) Renal arteriole effect caused by an acute increase in blood pressure.</li><ul> <li>Example-malignant hypertension</li> </ul><li>(2) Smooth muscle cell hyperplasia and basement membrane duplication</li> </ul><li>Arterioles have an "onion skin" appearance (see <span>[[Fig. 19-13|Figure 19-13]]</span>).</li> </ol> </ol> </ul>
</div></html>
<html><a name="HC009009"></a> <br><a name="P009010"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Abdominal aortic aneurysm: most common aneurysm in men > 55 years of age</blockquote>
<ol type="1"> <li>Usually located below the renal artery orifices</li><li>Pathogenesis</li><ol type="a"> <li>Atherosclerosis weakens vessel wall</li><ul> <li>(1) Vessel wall stress increases with vessel diameter.</li><li>(2) Lumen fills with atheromatous debris and blood clots (<span>[[Fig. 9-4|Figure 9-4]]</span>).</li> </ul><li>Familial factors, structural defects in connective tissue, no vasa vasorum</li> </ol><li>Clinical findings
<blockquote style="color: blue; ">Rupture triad: left flank pain, hypotension, pulsatile mass</blockquote></li><ol type="a"> <li>Usually asymptomatic</li><li>Rupture is the most common complication.</li><ul> <li>(1) Severe left flank pain is followed by hypotension from blood loss in the retroperitoneum.</li><li>(2) A pulsatile mass can be palpated.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC009010"></a> <br><a name="P009011"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Vessel wall weakening due to an infection</li><ul> <li>Does <i>not</i> have to be fungal</li> </ul><li>Fungi that invade vessels
<blockquote style="color: blue; ">Fungal vessel invaders: <i>Aspergillus, Candida, Mucor</i></blockquote></li><ul> <li><i>Aspergillus, Candida, Mucor</i></li> </ul><li>Bacteria that invade vessels</li><ul> <li><i>Bacteroides fragilis, Pseudomonas aeruginosa, Salmonella</i> species</li> </ul> </ol><li>Clinical findings
<blockquote style="color: blue; ">Bacterial vessel invaders: <i>B. fragilis, P. aeruginosa, Salmonella</i></blockquote></li><ol type="a"> <li>Thrombosis with or without infarction</li><li>Rupture</li> </ol> </ol>
</div></html>
<html><a name="HC009011"></a> <br><a name="P009012"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Defect at the junction of communicating branches with main cerebral vessels (see <span>[[Fig. 25-19|Figure 25-19]]</span>)</li><ul> <li>Vessel lacks an internal elastic lamina and smooth muscle.</li> </ul><li>Risk factors for developing the aneurysm</li><ul> <li>(1) Normal hemodynamic stress</li><li>(2) Presence of hypertension of any cause</li><li>(3) Coarctation of the aorta
<blockquote style="color: blue; ">CNS berry aneurysms: junction communicating branch with main vessel</blockquote></li> </ul><li>Rupture releases blood into the subarachnoid space.</li> </ol><li>Clinical findings</li><ol type="a"> <li>Sudden onset of severe occipital headache</li><ul> <li>Described as the "worst headache I have ever had"</li> </ul><li>Nuchal rigidity from irritation of the meninges</li><li>Complications</li><ul> <li>(1) Death may occur shortly after the bleed.</li><li>(2) Rebleed, hydrocephalus, neurologic deficits</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC009012"></a> <br><a name="PB009005"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Aortic regurgitation</b> is a problem in closing the aortic valve. Because the aortic valve closes in diastole, the murmur occurs in early diastole as blood leaks back into the ventricle. The increase in left ventricular end-diastolic volume results in an increase in stroke volume (increased systolic pressure). Blood rapidly draining back into the left ventricle produces a drop in the diastolic pressure. The wide pulse pressure (difference between the systolic and diastolic pressure) is manifested by a hyperdynamic circulation (e.g., pulsating uvula, bounding pulses). Excessive blood dripping back onto the anterior mitral valve leaflet produces another diastolic murmur called the Austin Flint murmur. This finding indicates the need for aortic valve replacement.</div><a name="P009013"></a><div class="PA" style="color: black; "><ol type="1"> <li>Complication of tertiary syphilis due to <i>Treponema pallidum</i> (spirochete)</li><ul> <li>Usually occurs in men 40 to 55 years of age</li> </ul><li>Pathogenesis
<blockquote style="color: blue; ">Aortic arch aneurysm: tertiary syphilis; vasa vasorum vasculitis</blockquote></li><ol type="a"> <li><i>T. pallidum</i> infects the vasa vasorum of the ascending and transverse portions of aortic arch (<span>[[Fig. 9-5|Figure 9-5]]</span>).</li><ul> <li>(1) Vasculitis is called endarteritis obliterans.</li><li>(2) Characteristic plasma cell infiltrate is present in the vessel wall.</li> </ul><li>Vessel ischemia of the medial tissue leads to dilation of the aorta and aortic valve ring.</li> </ol><li>Clinical findings</li><ol type="a"> <li>Aortic valve regurgitation
<blockquote style="color: blue; ">Syphilitic aneurysm: produces aortic regurgitation; bounding pulses</blockquote></li><li>Brassy cough</li><ul> <li>Left recurrent laryngeal nerve is stretched by the aneurysm.</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC009013"></a> <br><a name="PB009006"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Marfan syndrome</b> is an autosomal dominant disorder resulting in the production of weak elastic tissue due to a defect in synthesizing fibrillin (missense mutation). Cardiovascular abnormalities dominate. Dilation of the ascending aorta may progress to aortic dissection or aortic regurgitation. Mitral valve prolapse is the most common valvular defect and is often associated with conduction defects causing sudden death. Skeletal defects include hypermobile joints, eunuchoid proportions (lower body length > upper body length, arm span > height), and arachnodactyly (spider hands; <span>[[Fig. 9-6A|Figure 9-6]]</span>). Dislocation of the lens is another finding, because the suspensory ligament holding the lens is composed of elastic tissue.</div><a name="P009014"></a><div class="PA" style="color: black; "><ol type="1"> <li>Epidemiology</li><ol type="a"> <li>Men with a mean age of 40 to 60 years with antecedent hypertension</li><ul> <li>Most common group</li> </ul><li>Young patients with a connective tissue disorder</li><ul> <li>Examples-Marfan syndrome, Ehlers-Danlos syndrome (EDS)
<blockquote style="color: blue; ">Most common cause of death in Marfan syndrome and EDS: aortic dissection</blockquote></li> </ul> </ol><li>Pathogenesis
<blockquote style="color: blue; ">Aortic dissection: cystic medial degeneration</blockquote></li><ol type="a"> <li>Cystic medial degeneration (CMD)</li><ul> <li>(1) Elastic tissue fragmentation</li><li>(2) Matrix material collects in areas of fragmentation in the tunica media.</li> </ul><li>Risk factors for CMD</li><ul> <li>(1) Increase in wall stress</li><ul> <li>Hypertension, pregnancy (increased plasma volume), coarctation</li> </ul><li>(2) Defects in connective tissue</li><ul> <li>Marfan syndrome (defect in elastic tissue), EDS (defect in collagen)</li> </ul> </ul><li>Intimal tear</li><ul> <li>(1) Due to hypertension or underlying structural weakness in the media</li><li>(2) Usually occurs within 10 cm of the aortic valve (<span>[[Fig. 9-6B|Figure 9-6]]</span>)</li><li>(3) Blood dissects under arterial pressure through areas of weakness.</li><li>(4) Blood dissects proximally and/or distally (<span>[[Fig. 9-6C|Figure 9-6]]</span>).</li> </ul> </ol><li>Clinical findings
<blockquote style="color: blue; ">Aortic dissection: pain radiates into the back; absent pulse</blockquote></li><ol type="a"> <li>Acute onset of severe retrosternal chest pain radiating to the back</li><li>Aortic valve regurgitation</li><ul> <li>(1) Due to aortic valve ring dilation</li><li>(2) A radiograph or echocardiogram shows widening of the aortic valve root (<span>[[Fig. 9-6D|Figure 9-6]]</span>).</li> </ul><li>Loss of the upper extremity pulse</li><ul> <li>Due to compression of the subclavian artery</li> </ul><li>Rupture
<blockquote style="color: blue; ">Aortic dissection: cardiac tamponade most common cause of death</blockquote></li><ul> <li>Usually into the pericardial sac, pleural cavity, or peritoneal cavity</li> </ul> </ol> </ol>
</div></html>
![[9.III.A.Abdominal aortic aneurysm]]
<<tiddler [[9.III.A.Abdominal aortic aneurysm]]>>
![[9.III.B.Mycotic aneurysm]]
<<tiddler [[9.III.B.Mycotic aneurysm]]>>
![[9.III.C.Berry aneurysm of cerebral arteries]]
<<tiddler [[9.III.C.Berry aneurysm of cerebral arteries]]>>
![[9.III.D.Syphilitic aneurysm]]
<<tiddler [[9.III.D.Syphilitic aneurysm]]>>
![[9.III.E.Aortic dissection]]
<<tiddler [[9.III.E.Aortic dissection]]>>
<html><a name="HC009015"></a> <br><a name="P009019"></a><div class="PA" style="color: black; "><ol type="1"> <li>Superficial veins drain blood into the deep veins via penetrating branches.</li><li>Valves prevent reversal of blood flow into the superficial system.</li><li>Deep veins direct blood back to the heart.</li> </ol>
</div></html>
<html><a name="HC009016"></a> <br><a name="P009020"></a><div class="PA" style="color: black; "><ol type="1"> <li>Abnormally distended, lengthened, and tortuous veins</li><li>Locations</li><ol type="a"> <li>Superficial saphenous veins (most common site)</li><li>Distal esophagus (due to portal hypertension)</li><li>Anorectal region (e.g., hemorrhoids)</li><li>Left scrotal sac (e.g., varicocele)</li> </ol><li>Superficial varicosities; causes:
<blockquote style="color: blue; ">Superficial varicosities: valve incompetence</blockquote></li><ol type="a"> <li>Valve incompetence of perforator branches with reversal of blood flow from high-pressure deep venous system into superficial system</li><ul> <li>Exacerbated by pregnancy, prolonged standing, obesity, oral contraceptives, advanced age</li> </ul><li>Familial tendency</li><li>Secondary to deep venous thrombosis</li><ul> <li>Retrograde blood flow through perforating branches into the superficial system</li> </ul><li>Treatment</li><ul> <li>(1) Nonpharmacologic</li><ul> <li>Graded compression stockings</li> </ul><li>(2) Chronic treatment</li><ul> <li>(a) Compression sclerotherapy</li><li>(b) Ligation and stripping</li><li>(c) Endovenous obliteration using radiofrequency (diathermy) or laser</li> </ul> </ul> </ol> </ol>
</div></html>
<html><a name="HC009017"></a> <br><a name="P009021"></a><div class="PA" style="color: black; "><ol type="1"> <li>Thrombosis of a vein <i>without</i> inflammation</li><li>Causes
<blockquote style="color: blue; ">Phlebothrombosis: stasis of blood flow most common cause</blockquote></li><ol type="a"> <li>Stasis of blood flow</li><li>Hypercoagulability (e.g., antithrombin III deficiency)</li> </ol><li>Location</li><ol type="a"> <li>Most often occurs in the deep vein of the calf</li><li>Less common sites include portal vein, hepatic vein, dural sinuses.</li> </ol><li>Clinical findings associated with deep vein thrombosis</li><ol type="a"> <li>General findings</li><ul> <li>(1) Swelling</li><li>(2) Pain on dorsiflexion of foot (Homans' sign) and compression of the calf</li><li>(3) Pitting edema distal to the thrombosis (increased hydrostatic pressure)</li> </ul><li>Pulmonary thromboembolism</li><ul> <li>Occurs when the thrombus extends into the femoral vein</li> </ul><li>Deep venous insufficiency</li><ul> <li>(1) Stasis dermatitis (<span>[[Fig. 9-7|Figure 9-7]]</span>)
<blockquote style="color: blue; ">Stasis dermatitis: sign of DVT</blockquote></li><ul> <li>(a) Orange discoloration (hemosiderin) and ischemic ulcers (poor O<sub>2</sub> perfusion) around the ankles</li><li>(b) Caused by rupture of the penetrating branches</li><ul> <li>Due to back-up of pressure (retrograde blood flow) from chronic deep vein insufficiency (related to deep vein thromboses [DVTs], trauma, pregnancy)</li> </ul><li>(c) Treatment</li><ul> <li>Topical high potency corticosteroids; antibiotics if infection is present</li> </ul> </ul><li>(2) Varicosities develop in the superficial system</li><ul> <li>Due to retrograde blood flow into the superficial system from the blocked deep vein thrombosis</li> </ul> </ul><li>Diagnosis of DVT</li><ul> <li>Compression venous ultrasonography + serum <span style="font-variant:small-caps;">d</span>-dimer assay (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>)</li> </ul><li>Treatment of DVT</li><ul> <li>(1) Low-molecular-weight heparin</li><li>(2) Compression stockings</li><li>(3) Long-term treatment (3-6 months) to prevent recurrent DVTs-warfarin therapy</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC009018"></a> <br><a name="P009022"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pain and tenderness along the course of a superficial vein
<blockquote style="color: blue; ">Thrombophlebitis: pain and tenderness overlying the vein</blockquote></li><li>Association with occult DVT in 20% of cases</li><li>Pathogenesis</li><ol type="a"> <li>Intravenous cannulation of veins</li><li>Infection (<i>Staphylococcus aureus</i>)</li><li>Carcinoma of the pancreatic head</li><ul> <li>(1) Produces superficial migratory thrombophlebitis</li><li>(2) Due to the release of thrombogenic substances by the cancer</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Tender and palpable cord</li><li>Erythema and edema of the overlying skin and subcutaneous tissue</li> </ol><li>Treatment</li><ol type="a"> <li>Warm, moist compresses</li><li>NSAIDs</li> </ol> </ol>
</div></html>
<html><a name="HC009019"></a> <br><a name="P009023"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Extrinsic compression of the superior vena cava
<blockquote style="color: blue; ">SVC syndrome: compression of SVC by primary lung cancer</blockquote></li><li>Due to a primary lung cancer (90% of cases)</li><ul> <li>Usually a small cell carcinoma of the lung</li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>"Puffiness" and blue to purple discoloration of the face, arms, and shoulders (see <span>[[Fig. 16-34|Figure 16-34]]</span>)</li><li>Retinal hemorrhage, stroke</li> </ol><li>Treatment</li><ul> <li>Radiation; stent to bypass obstruction</li> </ul> </ol>
</div></html>
<html><a name="HC009020"></a> <br><a name="P009024"></a><div class="PA" style="color: black; "><ol type="1"> <li>Pathogenesis</li><ol type="a"> <li>Compression of the neurovascular compartment in the neck</li><li>Causes</li><ul> <li>Cervical rib, spastic anterior scalene muscles, or positional change in the neck and arms
<blockquote style="color: blue; ">Thoracic outlet syndrome: common among weight lifters; tight scalenus muscles</blockquote></li> </ul> </ol><li>Clinical findings</li><ol type="a"> <li>Vascular signs (e.g., arm "falls asleep" while person is sleeping)</li><li>Nerve root signs (e.g., numbness, paresthesias)</li><li>Positive Adson test</li><ul> <li>Pulse disappears when the arm is outstretched and the patient looks to the side of the outstretched arm.</li> </ul> </ol><li>Treatment</li><ul> <li>Manipulation therapy; home exercise</li> </ul> </ol>
</div></html>
![[9.IV.A.Saphenous venous system]]
<<tiddler [[9.IV.A.Saphenous venous system]]>>
![[9.IV.B.Varicose veins]]
<<tiddler [[9.IV.B.Varicose veins]]>>
![[9.IV.C.Phlebothrombosis]]
<<tiddler [[9.IV.C.Phlebothrombosis]]>>
![[9.IV.D.Thrombophlebitis]]
<<tiddler [[9.IV.D.Thrombophlebitis]]>>
![[9.IV.E.Superior vena cava (SVC) syndrome]]
<<tiddler [[9.IV.E.Superior vena cava (SVC) syndrome]]>>
![[9.IV.F.Thoracic outlet syndrome]]
<<tiddler [[9.IV.F.Thoracic outlet syndrome]]>>
<html><a name="HC009022"></a> <br><a name="P009026"></a><div class="PA" style="color: black; "><ul> <li>Lymphatic vessels have incomplete basement membranes, which predisposes them to infection and tumor invasion.</li> </ul>
</div></html>
<html><a name="HC009023"></a> <br><a name="P009027"></a><div class="PA" style="color: black; "><ol type="1"> <li>Inflammation of lymphatics ("red streak")</li><li>Usually due to cellulitis caused by <i>Streptococcus pyogenes</i>
<blockquote style="color: blue; ">Acute lymphangitis: <i>Streptococcus pyogenes</i> cellulitis</blockquote></li> </ol>
</div></html>
<html><a name="HC009024"></a> <br><a name="P009028"></a><div class="PA" style="color: black; "><ul> <li>Sporotrichosis (refer to <span macro="tag [[24 Skin Disorders]] [[Chapter 24]]"></span>)</li> </ul>
</div></html>
<html><a name="HC009025"></a> <br><a name="P009029"></a><div class="PA" style="color: black; "><ol type="1"> <li>Collection of lymphatic fluid in interstitial tissue or body cavities</li><li>Obstructive lymphedema</li><ol type="a"> <li>Radiation damage following radical mastectomy (<span>[[Fig. 9-8|Figure 9-8]]</span>)</li><li>Complex decongestive therapy</li><ul> <li>Leg elevation, limb massage, pneumatic leg compression</li> </ul> </ol><li>Turner's syndrome (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>)
<blockquote style="color: blue; ">Turner's webbed neck: lymphatic abnormality</blockquote></li><ol type="a"> <li>Lymphedema of hands and feet in newborns caused by defective lymphatics</li><li>Dilated lymphatic channels in the neck (cystic hygroma) produce webbed neck (see <span>[[Fig. 5-16|Figure 5-16]]</span>).</li> </ol><li>Chylous effusions (e.g., pleural cavity)</li><ol type="a"> <li>Contain chylomicrons with triglyceride plus mature lymphocytes</li><li>Damage to thoracic duct</li><ul> <li>Causes include malignant lymphoma, trauma</li> </ul> </ol> </ol>
</div></html>
![[9.V.A.Structure of lymphatic vessels]]
<<tiddler [[9.V.A.Structure of lymphatic vessels]]>>
![[9.V.B.Acute lymphangitis]]
<<tiddler [[9.V.B.Acute lymphangitis]]>>
![[9.V.C.Nodular lymphangitis]]
<<tiddler [[9.V.C.Nodular lymphangitis]]>>
![[9.V.D.Lymphedema]]
<<tiddler [[9.V.D.Lymphedema]]>>
<html><a name="HC009027"></a> <br><a name="P009031"></a><div class="PA" style="color: black; "><ul> <li>Most tumors derive from small vessels or arteriovenous anastomoses in glomus bodies.</li> </ul>
</div></html>
<html><a name="HC009028"></a><span>[[Fig. 9-9|Figure 9-9]]</span> <br><span>[[Table 9-1|Table 9-1. VASCULAR TUMORS AND TUMOR-LIKE CONDITIONS]]</span> <br> <br><a name="P009032"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Bacillary angiomatosis: <i>Bartonella henselae</i>; common in AIDS</blockquote>
</div></html>
![[9.VI.A.Tumors]]
<<tiddler [[9.VI.A.Tumors]]>>
![[9.VI.B.Vessel tumors and tumor-like conditions (Table 9-1 and Fig. 9-9)]]
<<tiddler [[9.VI.B.Vessel tumors and tumor-like conditions (Table 9-1 and Fig. 9-9)]]>>
<html><a name="HC009030"></a> <br><a name="P009034"></a><div class="PA" style="color: black; "><ol type="1"> <li>Type III hypersensitivity (immunocomplex)</li><ul> <li>Example-Henoch-Schönlein purpura</li> </ul><li>Type II hypersensitivity (antigen-antibody)</li><ul> <li>Example-Goodpasture syndrome (anti-basement membrane antibodies)</li> </ul><li>Antineutrophil cytoplasmic antibodies (ANCA)
<blockquote style="color: blue; ">ANCA: antibodies against components of neutrophils</blockquote></li><ol type="a"> <li>Activate neutrophils causing release of their enzymes and free radicals resulting in vessel damage</li><li>c-ANCA type</li><ul> <li>(1) Antibodies are directed against proteinase 3 in cytoplasmic granules.</li><li>(2) Example-Wegener's granulomatosis</li> </ul><li>p-ANCA type</li><ul> <li>(1) Antibodies are directed against myeloperoxidase.</li><li>(2) Examples-microscopic polyangiitis, Churg-Strauss syndrome</li> </ul><li>Direct invasion by all classes of microbial pathogens</li> </ol> </ol>
</div></html>
<html><a name="HC009031"></a> <br><a name="PB009007"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Purpura</b> due to thrombocytopenia or vessel instability (e.g., scurvy) is <i>not</i> palpable, because acute inflammation is <i>not</i> involved.</div><a name="P009035"></a><div class="PA" style="color: black; "><ol type="1"> <li>Small vessel vasculitis
<blockquote style="color: blue; ">Small vessel vasculitis: palpable purpura</blockquote></li><ol type="a"> <li>Called leukocytoclastic venulitis or hypersensitivity vasculitis</li><li>Gross appearance</li><ul> <li>(1) Skin overlying the vasculitis is hemorrhagic, raised, and painful to palpation.</li><ul> <li>Called palpable purpura ("tumor" of acute inflammation)</li> </ul><li>(2) Examples-Henoch-Schönlein purpura, microscopic polyangiitis</li> </ul><li>Microscopic appearance</li><ul> <li>Vessel is disrupted and contains a neutrophilic infiltrate associated with nuclear debris and fibrinoid necrosis.</li> </ul> </ol><li>Medium-sized vessel vasculitis
<blockquote style="color: blue; ">Medium-sized vessel vasculitis: thrombosis, aneurysm formation</blockquote></li><ol type="a"> <li>Muscular artery vasculitis</li><li>Presents with vessel thrombosis and infarction or aneurysms</li><li>Examples-polyarteritis nodosa, Kawasaki disease</li> </ol><li>Large vessel vasculitis
<blockquote style="color: blue; ">Large vessel vasculitis: absent pulse, stroke</blockquote></li><ol type="a"> <li>Elastic artery vasculitis</li><li>Presents with loss of a pulse or stroke</li><li>Examples-Takayasu arteritis, giant cell (temporal arteritis)</li> </ol><li>Summary table of vasculitides (<span>[[Table 9-2|Table 9-2. VASCULITIC DISORDERS: ELASTIC ARTERY, MUSCULAR ARTERY, AND SMALL VESSEL]]</span> and <span>[[Fig. 9-10|Figure 9-10]]</span>)</li> </ol>
</div></html>
![[9.VII.A.Pathogenesis]]
<<tiddler [[9.VII.A.Pathogenesis]]>>
![[9.VII.B.Clinical findings]]
<<tiddler [[9.VII.B.Clinical findings]]>>
<html><a name="HC009033"></a> <br><a name="P009037"></a><div class="PA" style="color: black; "><ol type="1"> <li>Normal</li><ul> <li><120 mm Hg systolic and <80 mm Hg diastolic</li> </ul><li>Pre-hypertension</li><ul> <li>120 to 139 mm Hg systolic or 80 to 89 mm Hg diastolic</li> </ul><li>Stage 1 hypertension</li><ul> <li>140 to 159 mm Hg systolic or 90 to 99 mm Hg diastolic</li> </ul><li>Stage 2 hypertension</li><ul> <li>≥160 mm Hg systolic or ≥100 mm Hg</li> </ul> </ol>
</div></html>
<html><a name="HC009034"></a> <br><a name="PB009008"></a><div class="BB" style="color: rgb(47, 79, 79); ">Factors that contract arteriole smooth muscle cells causing vasoconstriction include α-adrenergic stimuli, catecholamines, angiotensin II, vasopressin, and increased total body sodium.</div><a name="P009038"></a><div class="PA" style="color: black; "><ol type="1"> <li>Systolic blood pressure</li><ol type="a"> <li>Correlates with stroke volume</li><li>Determination of stroke volume:
<blockquote style="color: blue; ">Systolic blood pressure: correlates with stroke volume</blockquote></li><ul> <li>(1) Blood volume (equates with sodium homeostasis)</li><li>(2) Force of contraction</li><li>(3) Heart rate</li> </ul> </ol><li>Diastolic blood pressure</li><ol type="a"> <li>Determination of diastolic blood pressure
<blockquote style="color: blue; ">Diastolic blood pressure: correlates with tonicity of TPR arterioles</blockquote></li><ul> <li>(1) Volume of blood in the arteries while the heart is filling in diastole</li><ul> <li>Depends on the vascular tone of the peripheral resistance arterioles</li> </ul><li>(2) Elastic recoil of the aorta</li> </ul><li>Role of the total peripheral resistance (TPR) arterioles</li><ul> <li>(1) Abbreviated Poiseuille's equation</li><ul> <li>TPR = viscosity of blood/(radius of arteriole)<sup>4</sup></li> </ul><li>(2) Vasodilation decreases TPR</li><ul> <li>(a) Decreases diastolic blood pressure</li><li>(b) Increases venous return to the heart</li><li>(c) Vasodilators</li><ul> <li>Nitric oxide, prostaglandin I<sub>2</sub>, histamine, β-blockers, and calcium-channel blockers</li> </ul> </ul><li>(3) Vasoconstriction increases TPR.</li><ul> <li>Increases diastolic blood pressure</li> </ul> </ul> </ol><li>Role of sodium in hypertension
<blockquote style="color: blue; ">Pathogenesis hypertension: renal retention of sodium commonly involved</blockquote></li><ol type="a"> <li>Excess sodium increases plasma volume.</li><ul> <li>Increases stroke volume and systolic blood pressure</li> </ul><li>Excess sodium produces vasoconstriction of TPR arterioles</li><ul> <li>(1) Sodium enters arteriole smooth muscle cells and opens calcium channels, causing vasoconstriction.</li><li>(2) Increases diastolic blood pressure</li> </ul> </ol> </ol>
</div></html>
<html><a name="HC009035"></a> <br><a name="PB009009"></a><div class="BB" style="color: rgb(47, 79, 79); ">Reduced renal sodium excretion is the primary mechanism of essential hypertension in blacks and the elderly. Increased plasma volume suppresses renin release from the juxtaglomerular apparatus (low renin hypertension).</div><a name="P009039"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Most common type of hypertension: essential hypertension</blockquote>
<ol type="1"> <li>Accounts for 95% of cases of hypertension</li><li>Pathogenesis</li><ol type="a"> <li>Genetic factors reduce renal sodium excretion.</li><li>Unknown factors cause vasoconstriction of arterioles.</li><li>Obesity, stress</li> </ol> </ol>
</div></html>
<html><a name="HC009036"></a> <br><a name="P009040"></a><div class="PA" style="color: black; "><ol type="1"> <li>Accounts for 5% of cases of hypertension</li><li>Renovascular hypertension
<blockquote style="color: blue; ">Renovascular hypertension: most common cause of secondary hypertension</blockquote></li><ol type="a"> <li>Causes</li><ul> <li>(1) Elderly men</li><ul> <li>Atherosclerotic plaque partially blocks blood flow at the renal artery orifice (<span>[[Fig. 9-11|Figure 9-11]]</span>).</li> </ul><li>(2) Young to middle-aged women
<blockquote style="color: blue; ">Renovascular hypertension: atherosclerosis in men; fibromuscular hyperplasia in women</blockquote></li><ul> <li>Fibromuscular hyperplasia occurs in multifocal areas of the renal artery (<span>[[Fig. 9-12|Figure 9-12]]</span>).</li> </ul> </ul><li>Pathogenesis</li><ul> <li>(1) Decreased renal arterial blood flow activates the renin-angiotensin-aldosterone (RAA) system.
<blockquote style="color: blue; ">Renovascular hypertension: activation of RAA system</blockquote></li><li>(2) Angiotensin II vasoconstricts TPR arterioles.</li><li>(3) Aldosterone increases sodium retention.</li> </ul><li>Clinical findings</li><ul> <li>(1) Severe, uncontrollable hypertension</li><li>(2) Increased plasma renin activity (PRA)</li><li>(3) Involved kidney has increased PRA in the renal vein.
<blockquote style="color: blue; ">PRA: ↑ in involved kidney; ↓ in unaffected kidney</blockquote></li><li>(4) Uninvolved kidney has decreased PRA.</li><ul> <li>Increased plasma volume due to aldosterone excess suppresses RAA system in normal kidney.</li> </ul><li>(5) Epigastric bruit</li><ul> <li>Sound is due to turbulence of blood flow through the narrow renal artery.</li> </ul><li>(6) Angiography
<blockquote style="color: blue; ">Fibromuscular hyperplasia: "beaded" appearance of renal artery</blockquote></li><ul> <li>(a) Involved kidney shows diminished size (atrophy) and delayed emptying.</li><li>(b) Renal artery has "beaded" appearance in fibromuscular hyperplasia.</li> </ul> </ul><li>Other causes of secondary hypertension (<span>[[Table 9-3|Table 9-3. CAUSES OF SECONDARY HYPERTENSION]]</span>)</li> </ol> </ol>
</div></html>
<html><a name="HC009037"></a><span>[[Box 9-1|BOX 9-1 HYPERTENSIVE RETINOPATHY]]</span> <br><span>[[Table 9-4|Table 9-4. COMPLICATIONS OF HYPERTENSION]]</span> <br> <br><a name="P009041"></a><div class="PA" style="color: black; "><blockquote style="color: blue; ">Complications descending order: acute MI, stroke, renal failure</blockquote>
</div><a name="PB009010"></a><div class="BB" style="color: rgb(47, 79, 79); "><b>Nonpharmacologic treatment</b> of hypertension includes weight loss (most important), limited alcohol intake, aerobic exercise (30 min/day), reduced sodium intake (<1 mmol/day or <2.3 g/day), adequate potassium intake (>3500 mg/day), cessation of smoking, and a cholesterol lowering diet. For pre-hypertension, the lifestyle modifications listed above are recommended to bring the blood pressure under 130/80 mm Hg. For stage 1 hypertension, diuretics are preferred for initial therapy. More selective therapy is used if different disorders are present (e.g., congestive heart failure or diabetes-ACE inhibitor). For stage 2 hypertension, two drug combinations are required (e.g., diuretic + angiotensin II inhibitor). For pregnant women with hypertension (>130/80 mm Hg), the following drugs can be used: methyldopa, hydralazine, labetalol, or atenolol.</div><a name="PB009011"></a><div class="BB" style="color: rgb(47, 79, 79); ">Control of hypertension has its greatest benefit in reducing the incidence of strokes; however, it also significantly reduces the risk for developing CHD and renal disease.</div><a name="B009001"></a><div class="BT">BOX 9-1 HYPERTENSIVE RETINOPATHY</div><a name="PB009012"></a><div class="BB" style="color: rgb(47, 79, 79); "><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-009-g001.jpg" id=""><br>The sequence of events in hypertensive retinopathy involves focal spasm of the arterioles followed by progressive sclerosis and narrowing of the arterioles, leading eventually to flame hemorrhages from rupture of the vessels, formation of exudates (soft and hard), and papilledema (swelling of the optic disk). Normal arteriole walls are transparent; hence, the column of blood is visible and the light reflex is narrow. Sclerotic changes in the vessels are first described as "copper wiring," since blood is still visible through the vessel wall. The light reflex becomes wider. When the vessel wall is thickened enough to prevent visualization of the blood, the light reflects back from the vessel wall to produce a "silver wiring" effect. In some cases, no blood is visible in portions of the vessel. Because arterioles cross over the veins (normal ratio of arteriole to venous diameters is 3:4), as arterioles thicken they create a depression in the wall of the venule, which is called an arteriovenous (AV) nicking defect. The distal vein becomes slightly distended owing to the backup of blood. More advanced nicking literally cuts off the blood flow, and the veins appear to end abruptly. Hemorrhages in the retina are usually the result of rupture of microaneurysms that develop from increased pressure on the arterioles. Grayish-white exudates that are soft, like cotton wool, are due to microinfarctions, whereas exudates that have clear margins (hard exudates) are due to leakage of protein from increased vessel permeability. A brief summary of the Keith-Wagener-Barker classification of hypertensive retinopathy follows:
<ul> <li>Grade I: focal narrowing of the arterioles, mild AV nicking</li><li>Grade II: arteriole narrowing, copper wiring present, AV nicking more accentuated</li><li>Grade III: arteriole narrowing, silver wiring present, hemorrhages, soft and hard exudates, disappearance of the vein under the arteriole, disk normal</li><li>Grade IV: arterioles are fine fibrous cords; same as grade III except papilledema is present</li> </ul></div></html>
![[9.VIII.A.Classification]]
<<tiddler [[9.VIII.A.Classification]]>>
![[9.VIII.B.Pathophysiology of hypertension]]
<<tiddler [[9.VIII.B.Pathophysiology of hypertension]]>>
![[9.VIII.C.Essential hypertension]]
<<tiddler [[9.VIII.C.Essential hypertension]]>>
![[9.VIII.D.Secondary hypertension]]
<<tiddler [[9.VIII.D.Secondary hypertension]]>>
![[9.VIII.E.Complications of hypertension (Table 9-4 and Box 9-1)]]
<<tiddler [[9.VIII.E.Complications of hypertension (Table 9-4 and Box 9-1)]]>>
Go to tiddler: <<gotoTiddler search>>
/%<<toggleSideBar "Toggle right sidebar" "Toggle list of tags" hide>>%/
<<upload http://goljanpathology.tiddlyspot.com/store.cgi index.html . . goljanpathology>>
<html><a title="Save this site to a local file on your computer" href='http://goljanpathology.tiddlyspot.com/download' class='button'>Download</a></html> <html> </html>
<html><span class='button' onclick="refreshAll()" style="cursor:pointer">Refresh page</span></html>
<<tiddler OptionsPanel>>
*Saving notes/annotations only works when you have downloaded a local copy of the book to your hard drive (see [[Local copy]])
----
Edit mode:
*In edit mode, you can highlight and annotate sections
*To enable edit mode, click {{button{edit mode}}} in the top menu: it should change to {{button{edit mode •}}}
*To enter edit mode for a particular section, click {{button{edit+}}} under the heading or in the toolbar
*The top menu will display the number of edited but unsaved sections. To save changes to all sections, click {{button{save changes}}} in the dropdown menu there, or in the {{{options}}} menu (a new backup will be saved as well, see below)
*Edit mode is __''powerful''__: if you're not careful, you can delete content. In case of any accidents while editing, try the following:
**first try undoing ({{{Ctrl-Z}}})
**click {{button{cancel}}} or press {{{ESC}}} to revert to the last version of the section
**exit the book without saving, to lose any changes and reset to the most previous version of the book file
**use a previous backup of the book file (see below)
**sync to a fresh version of the section by clicking {{button{reload}}} in the toolbar of a section (need to be online for this to work)
----
Creating links:
*To insert a link to a section/figure/table/box inside the book or an external link, use the following format:
*{{{[[link location]]}}} or {{{[[link text|link location]]}}}
*the first version will display {{{link location}}} as the {{{link text}}}
*in the second version, the {{{link text}}} is explicitly specified
*{{{link location}}} does not have to be perfect: {{{[[1.I. Tissue Hypoxia]], [[1.I .Tissue hypoxia]], [[1.i. tissue hypoxia]]}}}, etc will all open [[1.I. Tissue Hypoxia]]
//example//: to link to Figure 1-1:
*{{{[[Ventilation-perfusion defects|Figure 1-1]]}}} → [[Ventilation-perfusion defects|Figure 1-1]]
*or: {{{[[Figure 1-1]]}}} → [[Figure 1-1]]
//example//: to link to a note:
*{{{[[note title]]}}} → [[note title]]
*If the note exists, clicking the link opens it. Otherwise, clicking the link opens a new note in edit mode.
*@@placing double brackets around //[[any text]]//, //anywhere// will create a link to a note with the title of the bracketed text@@
//example//: to link to {{{http://en.wikipedia.org/wiki/Ventilation/perfusion_ratio}}} :
*{{{[[V/Q ratio|http://en.wikipedia.org/wiki/Ventilation/perfusion_ratio]]}}}
*[[V/Q ratio|http://en.wikipedia.org/wiki/Ventilation/perfusion_ratio]]
----
*see [[Information]]
/***
|Name|AutoTaggerPlugin|
|Source|http://www.TiddlyTools.com/#AutoTaggerPlugin|
|Documentation|http://www.TiddlyTools.com/#AutoTaggerPluginInfo|
|Version|1.7.1|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|Tag tiddlers with date, author, etc. and/or scan the tiddler for any tags that are embedded in the content|
~AutoTagger ''automatically generates tag values for all newly created or edited tiddlers''
!!!!!Documentation
> see [[AutoTaggerPluginInfo]]
!!!!!Configuration
<<<
|<<option chkAutoTagAuthor>> add 'created by' author tag //(when a tiddler is first created)//||
|<<option chkAutoTagEditor>> add 'edited by' author tag //(when a tiddler is updated)//||
|<<option chkAutoTagDate>> add 'creation date' tag, using date format:|<<option txtAutoTagFormat>>|
|<<option chkAutoTagModDate>> add 'modification date' tag, using date format:|<<option txtAutoTagModFormat>>|
|<<option chkAutoTagNewTags>> add default tag(s) when creating new tiddlers:|<<option txtAutoTagNewTags>>|
|<<option chkAutoTagDefault>> add default tag(s) when saving tiddlers that are not otherwise tagged:|<<option txtAutoTagDefault>>|
|<<option chkAutoTagTrigger>> scan tiddler content for matching tags when tagged with:|<<option txtAutoTagTrigger>>|
|<<option chkAutoTagAliases>> replace 'aliased' tags using definitions contained in:|<<option txtAutoTagAliases>>|
|borderless|k
<<<
!!!!!Revisions
<<<
2008.03.29 [1.7.1] in displayTiddler(), get title from tiddler object (if needed).<br>Fixes errors caused when calling function passes a tiddler *object* instead of a tiddler *title*
2008.03.27 [1.7.0] added aliasing (using [[AutoTaggerAliases]] definition)
2008.03.11 [*.*.*] plugin size reduction - moved documentation to [[AutoTaggerPluginInfo]]
2007.10.18 [1.6.0] hijack displayTiddler() to add option to use default tags when creating new tiddlers (preloads tag edit field). Based on requests from RA and DavidWinfield.
| Please see [[AutoTaggerPluginInfo]] for previous revision details |
2005.08.15 [1.0.0] Initial Release
<<<
!!!!!Code
***/
//{{{
version.extensions.AutoTaggerPlugin= {major: 1, minor: 7, revision: 1, date: new Date(2008,3,29)};
var co=config.options; // shorthand temp variable
if (co.chkAutoTagDate==undefined) co.chkAutoTagDate=false;
if (co.chkAutoTagModDate==undefined) co.chkAutoTagModDate=false;
if (co.chkAutoTagEditor==undefined) co.chkAutoTagEditor=false;
if (co.chkAutoTagAuthor==undefined) co.chkAutoTagAuthor=false;
if (co.chkAutoTagTrigger==undefined) co.chkAutoTagTrigger=false;
if (co.txtAutoTagTrigger==undefined) co.txtAutoTagTrigger="auto";
if (co.chkAutoTagDefault==undefined) co.chkAutoTagDefault=false;
if (co.txtAutoTagDefault==undefined) co.txtAutoTagDefault="untagged";
if (co.txtAutoTagFormat==undefined) co.txtAutoTagFormat="YYYY.0MM.0DD";
if (co.txtAutoTagModFormat==undefined) co.txtAutoTagModFormat="YYYY.0MM.0DD";
if (co.chkAutoTagNewTags==undefined) co.chkAutoTagNewTags=false;
if (co.txtAutoTagNewTags==undefined) co.txtAutoTagNewTags="";
if (co.chkAutoTagAliases==undefined) co.chkAutoTagAliases=true;
if (co.txtAutoTagAliases==undefined) co.txtAutoTagAliases="AutoTaggerAliases";
// hijack displayTiddler()
Story.prototype.autotagger_displayTiddler=Story.prototype.displayTiddler;
Story.prototype.displayTiddler=function(srcElement,tiddler,template,animate,unused,customFields,toggle)
{
var title=(tiddler instanceof Tiddler)?tiddler.title:tiddler;
this.autotagger_displayTiddler.apply(this,arguments);
if (!config.options.chkAutoTagNewTags) return; // IF add new tags is enabled
if (!story.isDirty(title)) return; // AND tiddler is being edited
if (store.tiddlerExists(title)) return; // AND tiddler doesn't exist
var newtags=config.options.txtAutoTagNewTags.readBracketedList(); // get new tags
for (var t=0; t<newtags.length; t++)
story.setTiddlerTag(title,newtags[t],+1); // preload tag edit field
}
// hijack saveTiddler()
TiddlyWiki.prototype.autotagger_SaveTiddler=TiddlyWiki.prototype.saveTiddler;
TiddlyWiki.prototype.saveTiddler=function(title,newTitle,newBody,modifier,modified,tags,fields)
{
var co=config.options; // shorthand temp variable
var newTags = [];
if (tags) newTags = (typeof tags == "string") ? tags.readBracketedList() : tags;
var txt=store.getTiddlerText(config.options.txtAutoTagAliases,'')
if (config.options.chkAutoTagAliases && txt.length) {
// replace tag aliases with one or more other tags
var list=txt.split('\n');
var map={};
for (var i=0; i<list.length; i++)
map[list[i].split('=')[0]]=list[i].split('=')[1].readBracketedList();
for (var a in map) if (newTags.contains(a)) {
newTags.splice(newTags.indexOf(a),1); // remove alias
for (var i=0; i<map[a].length; i++) // add replacements
newTags.pushUnique(map[a][i]);
}
}
var now=new Date().formatString(co.txtAutoTagFormat);
if (co.chkAutoTagDate && (store.getTiddler(title)==undefined))
if (newTitle!=now) newTags.pushUnique(now); // created date - don't add to journals
if (co.chkAutoTagAuthor && (store.getTiddler(title)==undefined))
newTags.pushUnique(co.txtUserName); // creator
if (co.chkAutoTagEditor && store.getTiddler(title))
newTags.pushUnique(co.txtUserName); // modifier
if (co.chkAutoTagModDate && store.getTiddler(title))
newTags.pushUnique(new Date().formatString(co.txtAutoTagModFormat)); // modified
var allTags = store.getTags(); // scan content for tags
if (co.chkAutoTagTrigger && co.txtAutoTagTrigger.length && newTags.contains(co.txtAutoTagTrigger))
for (var t=0; t<allTags.length; t++) {
if (allTags[t][0]=='systemConfig') continue; // don't add 'systemConfig'
if ((newBody.indexOf(allTags[t][0])!=-1) || (newTitle.indexOf(allTags[t][0])!=-1))
newTags.pushUnique(allTags[t][0]); // autotag
}
for (var t=0; t<newTags.length; t++)
newTags[t]=String.encodeTiddlyLink(newTags[t]); // add brackets around tags
if (!newTags.length && co.chkAutoTagDefault && co.txtAutoTagDefault.length)
newTags.push(co.txtAutoTagDefault); // untagged - add default tag
arguments[5]=newTags.join(" ");
return this.autotagger_SaveTiddler.apply(this,arguments);
}
//}}}
/***
|Name|AutoTaggerPlugin|
|Source|http://www.TiddlyTools.com/#AutoTaggerPlugin|
|Documentation|http://www.TiddlyTools.com/#AutoTaggerPluginInfo|
|Version|1.7.1|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|documentation for AutoTaggerPlugin|
~AutoTagger ''automatically generates tag values for all newly created or edited tiddlers''
!!!!!Usage
<<<
Whenever you //create a new tiddler//, ~AutoTagger can add various tags for you:
* original author
* creation date
* default tag(s) (pre-loaded into tiddler editor)
* default tag(s) (when saving tiddlers that are not otherwise tagged)
Whenever you //edit an existing tiddler//, ~AutoTagger can add various tags for you:
* most recent author
* modification date
* default tag(s) (when saving tiddlers that are not otherwise tagged)
If you enter ''//auto//'' as a tiddler tag value, ~AutoTagger ''scans the tiddler content'' (including title) for text that matches any existing tags, and ''automatically adds any embedded tags that it finds''.
You can also create a tiddler that defines a set of [[AutoTaggerAliases]] to ''replace a single tag with one or more alternative tags''. The alias definitions use this format:
{{{
aliastag=tag1 tag2 tag3...
aliastag=tag4 tag5 tag6...
etc.
}}}
Notes:
* After the new tags have been added to the tiddler, they are treated just as if you had entered them by hand and can be edited to make any changes you want.
* As long as the "auto" tag is still present on a tiddler, ~AutoTagger will re-scan that tiddler's content each time it is edited. If you DO edit the generated tags, you can remove the "auto" tag from the tiddler to prevent it from being re-scanned when you press 'done' to finish editing. If you have set the "auto" tag on a tiddler, and then add several tags to your document, those tags will ''not'' be automatically added to the tiddler until you actually edit that tiddler and press 'done' to trigger an AutoTagger scan. The special-purpose ''"systemConfig" tag is never added automatically, even if matched in the tiddler content'', since this tag should be added manually to ensure it is always used appropriately.
*@@display:inline;Normally, aliases are removed and replaced by the indicated alternatives defined in the [[AutoTaggerAliases]] configuration. To retain an original alias tag (in addition to it's substitutes), include it in it's set of substitutes, like this:
{{{
aliastag=aliasgtag tag1 tag2 tag3...
}}}
@@
*@@display:inline;Alias definitions are processed in the order they occur in [[AutoTaggerAliases]]. If a given alias definition includes another alias that occurs after it in the configuration, the second alias will be replaced when it's definition is processed.
{{{
aliastag=tag1 anotheraliastag tag2...
anotheraliastag=tag3 tag4...
}}}
which results in: {{{tag1 tag2 tag3 tag4}}}
@@
<<<
!!!!!Configuration
<<<
|<<option chkAutoTagAuthor>> add 'created by' author tag //(when a tiddler is first created)//||
|{{{<<option chkAutoTagAuthor>>}}}||
|<<option chkAutoTagEditor>> add 'edited by' author tag //(when a tiddler is updated)//||
|{{{<<option chkAutoTagEditor>>}}}||
|<<option chkAutoTagDate>> add 'creation date' tag, using date format:|<<option txtAutoTagFormat>>|
|{{{<<option chkAutoTagDate>>}}}|{{{<<option txtAutoTagFormat>>}}}|
|<<option chkAutoTagModDate>> add 'modification date' tag, using date format:|<<option txtAutoTagModFormat>>|
|{{{<<option chkAutoTagModDate>>}}}|{{{<<option txtAutoTagModFormat>>}}}|
|<<option chkAutoTagNewTags>> add default tag(s) when creating new tiddlers:|<<option txtAutoTagNewTags>>|
|{{{<<option chkAutoTagNewTags>>}}}|{{{<<option txtAutoTagNewTags>>}}}|
|<<option chkAutoTagDefault>> add default tag(s) when saving tiddlers that are not otherwise tagged:|<<option txtAutoTagDefault>>|
|{{{<<option chkAutoTagDefault>>}}}|{{{<<option txtAutoTagDefault>>}}}|
|<<option chkAutoTagTrigger>> scan tiddler content for matching tags when tagged with:|<<option txtAutoTagTrigger>>|
|{{{<<option chkAutoTagTrigger>>}}}|{{{<<option txtAutoTagTrigger>>}}}|
|<<option chkAutoTagAliases>> replace 'aliased' tags using definitions contained in:|<<option txtAutoTagAliases>>|
|{{{<<option chkAutoTagAliases>>}}}|{{{<<option txtAutoTagAliases>>}}}|
|borderless|k
<<<
!!!!!Revisions
<<<
2008.03.29 1.7.1 in displayTiddler(), get title from tiddler object (if needed). Fixes errors caused when calling function passes a tiddler *object* instead of a tiddler *title*
2008.03.27 1.7.0 added aliasing (using [[AutoTaggerAliases]] definition)
2008.03.11 [*.*.*] plugin size reduction - moved documentation to [[AutoTaggerPluginInfo]]
2007.10.18 1.6.0 hijack displayTiddler() to add option to use default tags when creating new tiddlers (preloads tag edit field). Based on requests from RA and DavidWinfield.
2007.06.28 1.5.1 in hijack of saveChanges(), use apply() to allow additional params (such as "fields") to be correctly passed through to the core
2007.03.14 1.5.0 added support for tagging tiddlers with modification date
2007.01.20 1.4.1 don't add create date tag to dated journal tiddlers (based on request from ConalElliot)
2006.12.10 1.4.0 added option to use default tag value when no tags are specified
2006.08.29 1.3.3 use newTags.contains() instead of newTags.find() to check for 'auto' tag
2006.06.15 1.3.2 hijack TiddlyWiki.prototype.saveTiddler instead of store.saveTiddler. Permits other plugins to also hijack the function (thanks to Simon Baird for finding this!)
2006.05.31 1.3.1 Re-assemble tags into a space-separated string (use encodeTiddlyLink to add {{{[[...]]}}} as needed) before passing it on to core (or other hijacked function)
2005.10.09 1.3.0 Added 'edited by' tagging. Combined documentation and code into a single tiddler
2005.08.16 1.2.0 Added optional scanning for tags in tiddler content (based on suggestion from Jacques Turbé)
2005.08.15 1.1.0 Added 'created by' tag generation (based on suggestion from Elise Springer). Renamed from DateTag to AutoTagger
2005.08.15 1.0.0 Initial Release
<<<
List of boxes:
<<tagging>>
<html><a name="B001001"></a><a name="PB001014"></a><div style="margin-top: 5px; "><b>Enzymes</b> are protein catalysts of biologic origin that increase the rate of chemical reactions without themselves being consumed or structurally altered. <b>Isoenzymes</b> (isozymes) are multiple forms of the same enzyme that differ in stereotypical, biochemical, and immunologic properties (e.g., lactate dehydrogenase isoenzymes L<sub>1</sub>-L<sub>5</sub>; creatine kinase isoenzymes MM, MB, and BB). Measurement of individual isoenzymes is frequently more specific in identifying a disease than is total enzyme activity (e.g., CK-MB isoenzyme in identifying an acute myocardial infarction). <b>Isoforms</b> are subtypes of the individual isoenzymes (e.g., CK-MM isoforms).</div><a name="PB001015"></a><div style="margin-top: 5px; ">Enzymes distribute in cell membranes (e.g., alkaline phosphatase), endoplasmic reticulum (e.g., γ-glutamyltransferase), lysosomes (e.g., muramidase), zymogen (e.g., amylase), cytoplasm (e.g., alanine aminotransferase, a transaminase), and mitochondria (e.g., aspartate aminotransferase, a transaminase).</div><a name="PB001016"></a><div style="margin-top: 5px; ">Factors influencing the release of enzymes into body fluids include disruption or damage to the cell membrane (e.g., alanine aminotransferase, CK), increased synthesis owing to regeneration of injured cells (e.g., alkaline phosphatase), and enzyme induction in the smooth endoplasmic reticulum by drugs (e.g., alcohol and its effect on increasing γ-glutamyltransferase synthesis).</div><a name="PB001017"></a><div style="margin-top: 5px; ">The amount of enzyme released into body fluids depends on the amount of tissue injury, the rate of diffusion out of the damaged cell, and the overall rate of catabolism or clearance of the enzyme. The following table lists important enzymes that are increased in tissue injury.</div><div title="TI001001" id="TI001001"><table class="SCtable"><tbody><tr class="TH"><td align="CENTER" valign="BOTTOM"><b>Enzyme</b></td><td align="CENTER" valign="BOTTOM"><b>Diagnostic Use</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aspartate aminotransferase (AST) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Marker of diffuse liver cell necrosis (e.g., viral hepatitis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mitochondrial enzyme preferentially increased in alcohol-induced liver disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alanine aminotransferase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Marker of diffuse liver cell necrosis (e.g., viral hepatitis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> More specific for liver cell necrosis than AST </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Creatine kinase MB </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Isoenzyme increased in acute myocardial infarction or myocarditis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Amylase and lipase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Marker enzymes for acute pancreatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lipase more specific than amylase for pancreatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Amylase also increased in salivary gland inflammation (e.g., mumps) </td></tr></tbody></table><a name=""></a>
</div></html>
<html><a name="B010001"></a><a name="PB010003"></a><div style="margin-top: 5px; "><b>Valve Locations for Auscultation</b></div><a name="PB010004"></a><div style="margin-top: 5px; ">Locations where heart sounds are best heard do <i>not</i> always correlate with their anatomic location. The mitral valve (MV) is best heard at the apex; the tricuspid valve (TV) at the left parasternal border; the pulmonary valve (PV) at the left second and third intercostal spaces (ICS); and the aortic valve (AV) at the left sternal border for regurgitation murmurs and right second ICS for ejection murmurs.</div><a name="PB010005"></a><div style="margin-top: 5px; "><b>Cardiac Cycle Relationships with Heart Sounds</b></div><a name="PB010006"></a><div style="margin-top: 5px; ">The P wave represents atrial depolarization; the PR interval atrioventricular conduction time; the QRS ventricular depolarization; and the T wave ventricular repolarization, or recovery. The S<sub>1</sub> heart sound occurs at the same time as the QRS complex and marks the beginning of systole, while the S<sub>2</sub> heart sound occurs after the T wave and marks the beginning of diastole.</div><a name="PB010007"></a><div style="margin-top: 5px; "><b>Heart Sounds</b></div><a name="PB010008"></a><div style="margin-top: 5px; ">The <b>S<sub>1</sub> heart sound</b> corresponds with closure of the MV and TV during systole. The MV closes <i>before</i> the TV. It is best heard at the apex and corresponds with the carotid/radial pulse. The <b>S<sub>2</sub> heart sound</b> is caused by closure of the AV and PV and marks the beginning of diastole. It is best heard at the left second or third ICS. The aortic component (A<sub>2</sub>) normally precedes the pulmonary component (P<sub>2</sub>). Unlike the S<sub>1</sub> heart sound, the S<sub>2</sub> splits on inspiration. As the diaphragm descends, it causes a further decrease in negative intrathoracic pressure, which increases the flow of blood out of the vena cava into the right side of the heart. This causes flattening of the jugular neck veins. The excess amount of blood in the right side of the heart delays closure of the PV causing P<sub>2</sub> to separate away from A<sub>2</sub> (see schematic). This physiologic split is best heard over the PV area. A<sub>2</sub> and P<sub>2</sub> become a single sound on expiration as intrathoracic pressure becomes less negative. An <b>accentuated A<sub>2</sub></b> is heard in essential hypertension (increased pressure causes it to snap shut), while an <b>accentuated P<sub>2</sub></b> is heard in pulmonary hypertension.<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-010-g001.jpg" id=""></div><a name="PB010009"></a><div style="margin-top: 5px; ">An <b>S<sub>3</sub> heart sound</b> (see schematic) is the most clinically significant extra heart sound. It is a normal finding in children and young adults, where it reflects a more energetic expansion and filling of the left ventricle. However, it is considered a pathologic finding after 40 years of age. It is thought to be due to a sudden rush of blood entering a volume overloaded left or right ventricle. It is best heard at the apex with the patient in the left lateral decubitus position. It commonly occurs with regurgitant types of murmurs involving any of the valves. It is the first cardiac sign of congestive heart failure, where increased ventricular volume stretches the MV or TV ring causing volume overload from mitral/tricuspid regurgitation. An S<sub>3</sub> heart sound produces a ventricular gallop. An <b>S<sub>4</sub> heart sound</b> (see schematic) coincides with atrial contraction in late diastole and the a wave in the jugular venous pulse (JVP; see below). It is <i>never</i> a normal finding and is due to increased resistance to ventricular filling (decreased compliance) following a vigorous atrial contraction. It is heard best at the apex. Causes of decreased ventricular compliance include concentric ventricular hypertrophy (left/right) and a volume overloaded ventricle (no more room to expand). An S<sub>4</sub> heart sound and the a wave of a JVP are absent in atrial fibrillation. Presence of an S<sub>4</sub> heart sound produces an atrial gallop. Presence of an S<sub>3</sub> and S<sub>4</sub> heart sound is called a summation gallop (see schematic) and sounds like a galloping horse.<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-010-g002.jpg" id=""></div><a name="PB010010"></a><div style="margin-top: 5px; "><b>Heart Murmurs</b></div><a name="PB010011"></a><div style="margin-top: 5px; ">Heart murmurs may occur in systole and diastole. They may be caused by structural valve disease (e.g., damage due to rheumatic fever) or stretching of the valve ring (e.g., volume overload in left- or right-sided heart failure). Murmurs due to stretching of valve rings are often called functional murmurs. Murmurs often radiate. For example, AV stenosis radiates into the neck and MV regurgitation radiates into the axilla. They are graded 1 to 6 in terms of their intensity. Grade 1 and 2 murmurs are very hard to hear, while grade 3 murmurs are easy to hear. Grade 4 to 6 murmurs are often accompanied by a palpable precordial thrill. Grade 6 murmurs are audible without a stethoscope. Murmurs and abnormal heart sounds (e.g., S<sub>3</sub> and S<sub>4</sub> heart sounds) change their intensity with respirations. Right-sided murmurs and abnormal heart sounds have increased intensity when the patient takes a deep inspiration and holds the breath for 3 to 5 seconds. This is due to the increase in negative intrathoracic pressure drawing blood out of the venous system into the right side of the heart, hence accentuating the murmur and abnormal heart sound. In contradistinction, left-sided heart murmurs and abnormal heart sounds do <i>not</i> change their intensity with deep inspiration. <b>Continuous murmurs</b> occur through systole and diastole. The most common cause of a continuous murmur in children is a cervical venous hum. A patent ductus arteriosus also produces a continuous murmur. <b>Innocent murmurs</b> occur in children from 3 to 7 years old. They are usually grade 2 systolic murmurs that are caused by increased blood flow through the PV. They are best heard in the PV area, and as expected, their intensity increases with deep, held inspiration. <b>Stenosis murmurs</b> occur when there is a problem in opening the valves. Because the AV and PV normally open in systole, AV and PV stenosis occur in systole. They produce an ejection type murmur (schematic A), which has a diamond-shaped configuration. The MV and TV normally open in diastole; hence, the murmurs of MV and TV stenosis are heard in diastole. MV stenosis is accompanied by an opening snap (schematic B), which occurs when the thickened valve is forced open by a forceful atrial contraction. An opening snap is usually absent in TV stenosis. <b>Regurgitant (insufficiency) murmurs</b> occur when there is a problem in closing a valve. Because the MV and TV normally close in systole, these murmurs occur in systole. They are even-intensity pansystolic murmurs (schematic C) that often obliterate the S<sub>1</sub> and S<sub>2</sub> heart sounds. AV and PV regurgitant murmurs occur in diastole immediately after the S<sub>2</sub> heart sound (schematic D).<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-010-g003.jpg" id=""></div><a name="PB010012"></a><div style="margin-top: 5px; "><b>Jugular Venous Pulses (JVPs)</b></div><a name="PB010013"></a><div style="margin-top: 5px; "><b>Normal JVPs</b> (see schematic) have three positive waves (a, c, v) and two negative waves (x, y). The <b>a wave</b> is a positive wave due to atrial contraction in late diastole. It occurs after the P wave in an electrocardiogram. It disappears in atrial fibrillation. A <b>giant a wave</b> occurs when there is restricted filling of the right side of the heart (e.g., TV stenosis, pulmonary hypertension, right ventricular hypertrophy). The <b>c wave</b> is a positive wave due to right ventricular contraction in systole causing bulging of the TV into the right atrium producing increased pressure in the atrium and jugular vein. It correlates with the S<sub>1</sub> heart sound and the upstroke of the carotid pulse. The <b>x wave</b> is a large negative wave occupying most of systole. It is due to downward displacement of the TV when blood is ejected out of the RV into the pulmonary artery. The <b>v wave</b> is a positive wave that correlates with right atrial filling in systole when the TV is closed. The peak of the v wave marks the end of systole and beginning of diastole. A <b>giant c-v wave</b> occurs in TV regurgitation as blood refluxes back into the right atrium during systole. The <b>y wave</b> is a negative wave occupying most of diastole. It is due to opening of the TV with rapid flow of blood into the right ventricle in diastole.<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-010-g004.jpg" id=""></div></html>
<html><a name="B016001"></a><a name="PB016004"></a><div style="margin-top: 5px; ">Foreign material localizes to different portions of the lung, depending on the position of the patient. In the standing or sitting position, material localizes in the posterobasal segment of the right lower lobe; in the supine position, the superior segment of the right lower lobe; and in the right-sided position, the right middle lobe or the posterior segment of the right upper lobe. The most common aspiration site is the superior segment of the right lower lobe.<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-016-g002.jpg" id=""></div></html>
<html><a name="B018001"></a><a name="PB018001"></a><div style="margin-top: 5px; "><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-018-g001.jpg" id=""><br>In this discussion, the symbol (+) is used to indicate degrees of magnitude. <b>Normal bilirubin metabolism</b> (<b>A</b>) shows liver uptake of lipid-soluble unconjugated bilirubin (UCB) and its conjugation with glucuronic acid to produce water-soluble conjugated bilirubin (CB). CB is secreted into the common bile duct (CBD) and is emptied into the bowel. Intestinal bacteria convert CB to urobilinogen (UBG), which spontaneously oxidizes to the pigment urobilin. Urobilin is responsible for the color of stool. A small percentage of UBG is reabsorbed into the blood. Most of it enters the liver (<i>larger arrow</i>) and a small percentage (<i>smaller arrow</i>) enters the urine (UBG). Urobilin is responsible for the color of urine. All of the normal bilirubin in blood is UCB (CB% < 20%) primarily derived from macrophage destruction of senescent RBCs. UCB does <i>not</i> enter urine, because it is attached to albumin in the blood and is lipid, <i>not</i> water, soluble. CB is <i>never</i> a normal finding in urine because it does <i>not</i> have contact with blood in its metabolism.</div><a name="PB018002"></a><div style="margin-top: 5px; ">In <b>extravascular hemolysis</b> (<b>B</b>) (e.g., hereditary spherocytosis), there is increased macrophage production of UCB causing an increase in serum UCB (++) (CB% < 20%). There is a corresponding increase in uptake and conjugation of UCB, conjugation to CB (++), and conversion of CB in the bowel to UBG (++). This causes darkening of the stool. There is a greater percentage of UBG recycled back to the liver (<i>wider arrow</i>) and urine (<i>wider arrow</i>). The increase in urine UBG (++), darkens the color of urine. Because RBCs contain the enzyme aspartate aminotransferase (AST), hemolysis of RBCs causes an increase in serum AST. Alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) levels are normal.</div><a name="PB018003"></a><div style="margin-top: 5px; ">In <b>viral hepatitis</b> (<b>C</b>), there is generalized liver dysfunction involving uptake and conjugation of UCB, secretion of CB into bile ducts, and recycling of UBG. Serum UCB is increased (++) owing to a decrease in uptake and conjugation. Serum and urine CB are increased (++) because of liver cell necrosis and disruption of bile ductules between hepatocytes. Urine UBG is increased (++) because UBG is redirected from the liver (<i>smaller arrow</i>) to the kidneys (<i>larger arrow</i>). Because there is an increase in serum UCB and CB, there is a mixed hyperbilirubinemia with a CB% of 20% to 50%. In viral hepatitis, aLT is higher (+++) than AST (++) and there is a slight increase in ALP and GGT (+). In alcoholic hepatitis, AST is greater than ALT, because alcohol damages mitochondria, which is where AST is normally located.</div><a name="PB018004"></a><div style="margin-top: 5px; ">In <b>obstructive liver disease</b> (<b>D</b>), an increase in serum and urine CB (++) is due to obstruction of intrahepatic or extrahepatic bile flow (stone in the CBD in this case). This causes increased pressure in the intrahepatic bile ductules leading to rupture and egress of CB into sinusoidal blood. There is absence of UBG in the stool (light-colored) and urine. CB% > 50% and there is a marked increase in serum ALP and GGT (+++) and only a slight increase in serum AST and ALT (+).</div></html>
<html><a name="B019001"></a><a name="PB019006"></a><div style="margin-top: 5px; "><b>Oliguria</b> is defined as a urine output < 400 mL/day or <20 mL/hour. The major causes of oliguria include prerenal azotemia (most common cause), acute glomerulonephritis (nephritic type), acute tubular necrosis (renal azotemia), and postrenal azotemia. Laboratory tests that are commonly used in differentiating the types of oliguria include urine osmolality (UOsm), fractional excretion of sodium (FENa<sup>+</sup>), random urine sodium (UNa<sup>+</sup>), and the serum BUN:Cr (blood urea nitrogen/creatinine) ratio (see section III). These tests evaluate tubular function. A UOsm > 500 mOsm/kg indicates good concentrating ability and intact tubular function, but a UOsm < 350 mOsm/kg indicates poor concentrating ability and tubular dysfunction. The FENa<sup>+</sup> represents the amount of sodium excreted in the urine divided by the amount of sodium that is filtered by the kidneys. The calculation is as follows:
where UNa<sup>+</sup> is a random urine sodium, PNa<sup>+</sup> is serum sodium, UCr is random urine creatinine, and PCr is plasma creatinine. Creatinine is used in the formula, because the amount of sodium filtered is dependent on the glomerular filtration rate (GFR), which closely approximates the creatinine clearance (CCr). An FENa<sup>+</sup> < 1% indicates good tubular function and <i>excludes</i> acute tubular necrosis (ATN) as a cause of oliguria. An FENa<sup>+</sup> > 2% indicates tubular dysfunction and is highly predictive of ATN as the cause of oliguria. A random UNa<sup>+</sup> < 20 mEq/L indicates intact tubular function, while a random UNa<sup>+</sup> > 40 mEq/L indicates tubular dysfunction. A serum BUN:Cr ratio > 15 indicates intact tubular function, but a serum BUN:Cr ratio ≤ 15 indicates tubular dysfunction. In prerenal azotemia and acute glomerulonephritis (nephritic type) tubular function is preserved. In order to distinguish the two, the urine sediment examination is most useful. In prerenal azotemia, the urine sediment has <i>no</i> abnormal findings or may have a few hyaline casts. The sediment in acute glomerulonephritis (nephritic type) has hematuria and RBC casts. ATN and postrenal azotemia (long-standing obstruction) both have tubular dysfunction. Postrenal azotemia of short duration has normal tubular function and has laboratory findings similar to prerenal azotemia. In order to distinguish ATN from postrenal azotemia as a cause of tubular dysfunction and oliguria, the urine sediment is most useful. In ATN, the sediment has pigmented renal tubular cell casts, but in postrenal azotemia, the sediment is usually normal. In addition, the patient will likely have a history of a renal stone, benign prostatic hyperplasia, or cervical cancer, which commonly obstructs the ureters where they enter the urinary bladder.</div><div title="TI019001" id="TI019001"><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>Disorder</b></td><td align="LEFT" valign="BOTTOM"><b>FENa<sup>+</sup> %</b></td><td align="LEFT" valign="BOTTOM"><b>BUN:Cr</b></td><td align="LEFT" valign="BOTTOM"><b>UNa<sup>+</sup></b></td><td align="LEFT" valign="BOTTOM"><b>UOsm</b></td><td align="LEFT" valign="BOTTOM"><b>Urinalysis</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prerenal azotemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <1 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >15 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <20 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >500 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal sediment or hyaline casts </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute glomerulonephritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <1 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >15 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <20 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >500 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> RBC casts, hematuria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute tubular necrosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >2 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ≤15 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >40 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <350 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal tubular cell casts </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Postrenal azotemia (prolonged obstruction) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >2 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ≤15 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >40 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <350 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal sediment </td></tr></tbody></table><a name=""></a>
</div></html>
<html><a name="B002001"></a><a name="PB002005"></a><div style="margin-top: 5px; "><ul> <li>The tubercle bacillus <i>Mycobacterium tuberculosis</i> undergoes phagocytosis by alveolar macrophages (processing of bacterial antigen).</li><li>Macrophages present antigen to CD4 T cells in association with class II antigen sites.</li><li>Macrophages release interleukin (IL) 12 (stimulates naïve T<sub>H</sub> cells to produce T<sub>H</sub>1 class memory cells) and IL-1 (causes fever; activates T<sub>H</sub>1 cells).</li><li>T<sub>H</sub>1 cells release IL-2 (stimulates T<sub>H</sub>1 proliferation), γ-interferon (activates macrophages to kill tubercle bacillus; epithelioid cells), and migration inhibitory factor (causes macrophages to accumulate).</li><li>Lipids from killed tubercle bacillus lead to caseous necrosis.</li><li>Activated macrophages fuse and become multinucleated giant cells.</li> </ul></div></html>
<html><a name="B002002"></a><a name="PB002006"></a><div style="margin-top: 5px; "><ul> <b>Primary Intention</b><li>Day 1: Fibrin clot (hematoma) develops. Neutrophils infiltrate the wound margins. There is increased mitotic activity of basal cells of squamous epithelium in the apposing wound margins.</li><li>Day 2: Squamous cells from apposing basal cell layers migrate under the fibrin clot and seal off the wound after 48 hours. Macrophages emigrate into the wound.</li><li>Day 3: Granulation tissue begins to form. Initial deposition of type III collagen begins but does <i>not</i> bridge the incision site. Macrophages replace neutrophils.</li><li>Days 4-6: Granulation tissue formation peaks, and collagen bridges the incision site.</li><li>Week 2: Collagen compresses blood vessels in fibrous tissue, resulting in reduced blood flow. Tensile strength is ∼10%.</li><li>Month 1: Collagenase remodeling of the wound occurs (breaks peptide bonds), with replacement of type III collagen by type I collagen. Tensile strength increases, reaching ∼80% within 3 months. Scar tissue is devoid of adnexal structures (e.g., hair, sweat glands) and inflammatory cells.</li> </ul>
<ul> <b>Secondary Intention</b><li>Typically, these wounds heal differently from primary intention:</li><li>More intense inflammatory reaction than primary healing</li><li>Increased amount of granulation tissue formation than in primary healing</li><li>Wound contraction caused by increased numbers of myofibroblasts</li> </ul></div></html>
<html><a name="B025001"></a><a name="PB025002"></a><div style="margin-top: 5px; ">CSF derives from the choroid plexus in the ventricles and enters the subarachnoid space. It cushions the brain and spinal cord and transmits chemicals to reach other parts of the brain. CSF is reabsorbed by the arachnoid granulations and drained into dural venous sinuses, which eventually drain into the jugular vein.</div><a name="PB025003"></a><div style="margin-top: 5px; ">CSF normally is clear and colorless. <b>Turbidity</b> may be caused by an increase in protein, cells, microbial pathogens, or a combination of all three elements. <b>Bloody CSF</b> from spinal taps is most commonly iatrogenic but can also represent a pathologic hemorrhage into the subarachnoid space (e.g., ruptured berry aneurysm, intracerebral bleed near the surface of the brain or ventricles). If the bloody tap is iatrogenic, the supranate should be clear after centrifugation, particularly in the last tube collected in the spinal tap. In pathologic bleeds, there are sequential color changes that occur. CSF colors after centrifugation may be pink- or orange-tinged. A pink color is due to oxyhemoglobin (oxyHb) from ruptured red blood cells. It first occurs 2-4 hours post-bleed, peaks in 24-36 hours, and subsides in 4-8 days. A yellow to orange color (xanthochromia) is due to oxyHb breakdown into bilirubin. It first appears 12 hours post-bleed, peaks in 2-4 days, and subsides in 2-4 weeks. <b>CSF protein</b> normally is 15-45 mg/dL. CSF prealbumin and albumin derive from plasma; therefore, increased levels of these proteins must be due to increased capillary permeability (e.g., acute inflammation). <b>CSF gamma (γ) globulins</b> derive from the synthesis of IgG by plasma cells within the central nervous system (CNS). In a CSF electrophoresis, CSF γ-globulins account for <12% of the total protein. An increase in CSF IgG is due to either increased synthesis of IgG in the CNS (e.g., multiple sclerosis) or an increase in capillary vessel permeability in acute inflammation (e.g., meningitis). It is clinically important to make this distinction. A <b>CSF IgG index</b> (calculated with a formula) is useful in distinguishing acute inflammation from demyelinating diseases, the most common CNS disease producing an increase in IgG. An increase in the CSF IgG index correlates with a CNS origin of the IgG, and a decreased index indicates
acute inflammation. <b>Routine CSF electrophoresis</b> quantitates the amount of γ-globulins that are present when CSF protein is increased. <b>High-resolution CSF electrophoresis</b>, however, is most useful in detecting demyelinating disease, of which multiple sclerosis is the most common cause. Other demyelinating diseases include neurosyphilis and Guillain-Barré syndrome. High-resolution detects <b>oligoclonal bands</b> in the γ-globulin region (see <span>[[Fig. 25-27D|Figure 25-27]]</span>). These are discrete, discontinuous bands originating from single clones of immunocompetent B cells. Another test for demyelinating disease is <b>myelin basic protein (MBP),</b> a protein that is normally present in myelin. An increased CSF MBP occurs with active demyelinating disease. CSF MBP is decreased when a demyelinating disease is in remission.</div><a name="PB025004"></a><div style="margin-top: 5px; "><b>CSF glucose</b> does <i>not</i> have the same concentration as serum glucose. A normal value for CSF glucose is 50-75 mg/dL, but a normal value in serum glucose is 70-110 mg/dL. A rough estimate of what the CSF glucose should be is to multiply a serum sample value obtained 30-90 minutes <i>before</i> the lumbar puncture by 0.66. For example, if the serum glucose is 100 mg/dL, then the CSF glucose should be around 66 mg/dL. A decreased CSF glucose (hypoglycorrhachia) is defined as a glucose level < 40 mg/dL. It implies that there has been increased uptake of glucose by cellular elements in the CSF (e.g., neutrophils in acute bacterial meningitis, malignant cells) or a defect in the glucose carrier system (frequently occurs in bacterial/fungal meningitis). CSF glucose is usually normal in viral meningitis, neurosyphilis, demyelinating disease, and a cerebral abscess. Exceptions in which viral infections of the CNS produce a decreased CSF glucose include infections associated with mumps, herpes simplex, and the lymphocytic choriomeningitis virus. <b>CSF chloride</b> is usually greater than the serum chloride (limited usefulness). The <b>CSF white blood cell count</b> normally is 0-5 mononuclear cells/mm<sup>3</sup>. Neutrophils are <i>never</i> normal in the CSF. An increased CSF WBC count is most often due to meningitis caused by microbial pathogens. Bacterial meningitis usually has a predominance of neutrophils, while viral meningitis initially has a neutrophil response in the first 24 hours that changes to a predominantly lymphocytic response in 2-3 days. Fungal meningitis is characterized by a predominance of lymphocytes and monocytes. A parasitic meningitis usually has a mixed inflammatory infiltrate (eosinophils suggest a helminth infection). A <b>Gram stain</b> is useful for detecting bacteria (75-80% sensitivity) in the sediment after ultracentrifugation of the CSF. Other tests include culture, India ink for <i>Cryptococcus neoformans</i> (sensitivity is 50%), antigen detection (sensitivity depends on the pathogen; specificity is 96-100%), enzyme immunoassay (96-100% sensitivity/specificity), and polymerase chain reaction studies that detect DNA (sensitivity 94%, specificity 96%).</div></html>
<html><a name="B004001"></a><a name="PB004014"></a><div style="margin-top: 5px; ">Protection of the intravascular volume is paramount to normal survival. Maintenance of the extracellular fluid (ECF) volume involves the integration of factors that (1) control thirst (e.g., increased POsm and angiotensin II [ATII]), (2) activate the renin-angiotensin-aldosterone (RAA) system (e.g., reduced renal blood flow, sympathetic nervous system stimulation), (3) stimulate the baroreceptors in the arterial circulation (e.g., decreased effective arterial blood volume), (4) increase free water reabsorption to concentrate the urine (e.g., antidiuretic hormone), and (5) increase renal reabsorption of Na<sup>+</sup> and water.</div><a name="PB004015"></a><div style="margin-top: 5px; "><b>Effective Arterial Blood Volume</b></div><a name="PB004016"></a><div style="margin-top: 5px; "><b>Effective arterial blood volume (EABV)</b> is a conceptual term that refers to that portion of the ECF that is in the vascular space. In most instances, it correlates directly with the ECF volume and TBNa<sup>+</sup> status of the individual (i.e., ↓ EABV // ↓ ECF/↓ TBNa<sup>+</sup> or ↑ EABV // ↑ ECF/↑ TBNa<sup>+</sup>). However, in edema states, where there is an alteration in Starling pressures (e.g., right-sided heart failure), the redistribution of fluid (a transudate) from the intravascular compartment into the interstitial fluid compartment increases the total ECF volume at the expense of reducing the venous return of blood to the right side of the heart, reducing cardiac output, and reducing EABV (↓ EABV // ↑ ECF/↑ TBNa<sup>+</sup>). Hence, an increase in total ECF volume does not always correlate with an increase in the EABV.</div><a name="PB004017"></a><div style="margin-top: 5px; "><b>Baroreceptors and the Renin-Angiotensin-Aldosterone System</b></div><a name="PB004018"></a><div style="margin-top: 5px; ">Control of the EABV is monitored by the pressure impacting upon the high pressure arterial baroreceptors located in the aortic arch and carotid sinus, and the flow of blood to the renal arteries. When the baroreceptors are activated by a decreased EABV, signals are sent to the medulla to increase sympathetic tone leading to release of catecholamines resulting in vasoconstriction of peripheral resistance arterioles (increases diastolic blood pressure), venoconstriction (increases venous return to the heart), increases heart rate (chronotropic effect), and increases cardiac contractility (inotropic effect). Signals are also sent to the supraoptic and paraventricular nuclei in the hypothalamus to synthesize and release antidiuretic hormone (ADH, vasopressin), the latter from nerve endings located in the posterior pituitary. ADH enhances the reabsorption of free water (fH<sub>2</sub>O; water without electrolytes) from the collecting tubules in the kidneys and is a potent vasoconstrictor of the peripheral resistance vessels. Finally, the RAA system is activated owing to reduced blood flow to the juxtaglomerular (JG) apparatus located in the afferent arterioles and by direct sympathetic stimulation of the JG apparatus with subsequent release of the enzyme renin. Renin initiates the following reaction sequence: it cleaves renin substrate (angiotensinogen) into <b>angiotensin I</b> (ATI), which is converted by pulmonary <b>angiotensin converting enzyme</b> (ACE) into <b>angiotensin II</b> (ATII). ATII has a threefold function:
<ol type="1"> <li>Vasoconstriction of peripheral resistance arterioles</li><li>Stimulation of aldosterone synthesis and release from the zona glomerulosa (increases Na<sup>+</sup> reabsorption in exchange for potassium ions [K<sup>+</sup>] and hydrogen ions [H<sup>+</sup>])</li><li>Direct stimulation of the thirst center in the brain</li> </ol></div><a name="PB004019"></a><div style="margin-top: 5px; ">All of these events are an attempt to increase the EABV before medical intervention.</div><a name="PB004020"></a><div style="margin-top: 5px; ">In contradistinction, when there is an increase in EABV, there are many counterregulatory mechanisms that come into play to eliminate the excess fluid prior to medical intervention. An increase in EABV is associated with a corresponding increase in cardiac output. This stretches the arterial baroreceptors, which triggers cessation of sympathetic outflow from the medulla. This, in turn, leads to inhibition of ADH synthesis and release, vasodilation of peripheral resistance arterioles, decreased cardiac contraction, inhibition of the RAA system, and decreased renal retention of Na<sup>+</sup> and water. Other counterregulatory factors also come into play including <b>atrial natriuretic peptide</b> (ANP), <b>prostaglandin E<sub>2</sub></b>, and <b>brain natriuretic peptide (BNP)</b>. ANP is released from the left and right atria in response to atrial distention (e.g., left- and/or right-sided heart failure). ANP has multiple functions including (1) suppression of ADH release, (2) inhibition of the effect of ATII on stimulating thirst and aldosterone secretion, (3) vasodilation of the peripheral resistance vessels, (4) direct inhibition of Na<sup>+</sup> reabsorption in the kidneys (diuretic effect), and (5) suppression of renin release. Prostaglandin E<sub>2</sub> (1) inhibits ADH, (2) blocks Na<sup>+</sup> reabsorption in the kidneys, and (3) is a potent intrarenal vasodilator that offsets the vasoconstrictive effects of ATII and the catecholamines. BNP increases in the blood when the right and/or left ventricles are volume overloaded (e.g., left- and/or right-sided heart failure).</div><a name="PB004021"></a><div style="margin-top: 5px; "><b>Renal Mechanisms in Volume Regulation</b></div><a name="PB004022"></a><div style="margin-top: 5px; ">The response of the kidney to volume alterations is closely integrated with many of the events previously described. The reabsorption of solutes from the proximal tubules is dependent on the <b>filtration fraction</b> (FF) in the glomerulus in concert with Starling pressures that are operative in the peritubular capillaries. The FF is the fraction of the <b>renal plasma flow</b> (RPF) that is filtered across the glomerular capillaries into the tubular lumen. It is calculated by dividing the <b>glomerular filtration rate</b> (GFR) by the RPF (FF = GFR ÷ RPF). Normally, the FF is ∼20%, with the remaining 80% of the RPF entering the efferent arterioles, which divide to form the intricate peritubular capillary microcirculation. Because prostaglandin E<sub>2</sub>, a vasodilator, controls the afferent arteriolar blood flow into the glomerulus and ATII, a vasoconstrictor, monitors the efferent arteriolar blood flow leaving the glomerulus, the FF is significantly affected by alterations in their concentrations. Starling pressures in the peritubular capillaries determine how much of the fluid from the proximal tubule is reabsorbed back into the ECF compartment. A low peritubular capillary hydrostatic pressure (P<sub>H</sub>) coupled with a high oncotic pressure (P<sub>O</sub>) is responsible for enhancing the reabsorption of solutes from the tubular lumen into the tubular cell out into the lateral intercellular space, and into the peritubular capillary (A). This occurs when the EABV is decreased (e.g., ECF volume depletion, or hypovolemia). A high P<sub>H</sub> coupled with a low P<sub>O</sub> results in the loss of solutes in the urine in conditions when the EABV is increased (B; e.g., ECF volume overload, or hypervolemia). When hypovolemia is present in the ECF, the EABV is reduced and the FF is increased (↑FF = ↓GFR ÷ ↓↓RPF), hence increasing the filtered load of Na<sup>+</sup> and other solutes. The P<sub>H</sub> is decreased and the P<sub>O</sub> is increased, resulting in the reabsorption of the filtered Na<sup>+</sup> plus other solutes into the ECF compartment (e.g., urea) in isosmotic proportions. The above mechanism is so effective that a <b>random urine Na</b><sup>+</sup> (UNa<sup>+</sup>) measurement is usually < 20 mEq/L and is often 0 when hypovolemia is extreme. In the presence of an increased EABV, or hypervolemia, the FF is decreased (↓FF = ↑GFR ÷ ↑↑RPF), the filtered load of Na<sup>+</sup> and other solutes is decreased, the P<sub>H</sub> is increased and the P<sub>O</sub> is decreased, hence favoring loss of the filtered Na<sup>+</sup> plus other solutes (e.g., urea, uric acid) in the urine (random UNa<sup>+</sup> > 20 mEq/L).<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g011.jpg" id="">
</div></html>
<html><a name="B009001"></a><a name="PB009012"></a><div style="margin-top: 5px; "><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-009-g001.jpg" id=""><br>The sequence of events in hypertensive retinopathy involves focal spasm of the arterioles followed by progressive sclerosis and narrowing of the arterioles, leading eventually to flame hemorrhages from rupture of the vessels, formation of exudates (soft and hard), and papilledema (swelling of the optic disk). Normal arteriole walls are transparent; hence, the column of blood is visible and the light reflex is narrow. Sclerotic changes in the vessels are first described as "copper wiring," since blood is still visible through the vessel wall. The light reflex becomes wider. When the vessel wall is thickened enough to prevent visualization of the blood, the light reflects back from the vessel wall to produce a "silver wiring" effect. In some cases, no blood is visible in portions of the vessel. Because arterioles cross over the veins (normal ratio of arteriole to venous diameters is 3:4), as arterioles thicken they create a depression in the wall of the venule, which is called an arteriovenous (AV) nicking defect. The distal vein becomes slightly distended owing to the backup of blood. More advanced nicking literally cuts off the blood flow, and the veins appear to end abruptly. Hemorrhages in the retina are usually the result of rupture of microaneurysms that develop from increased pressure on the arterioles. Grayish-white exudates that are soft, like cotton wool, are due to microinfarctions, whereas exudates that have clear margins (hard exudates) are due to leakage of protein from increased vessel permeability. A brief summary of the Keith-Wagener-Barker classification of hypertensive retinopathy follows:
<ul> <li>Grade I: focal narrowing of the arterioles, mild AV nicking</li><li>Grade II: arteriole narrowing, copper wiring present, AV nicking more accentuated</li><li>Grade III: arteriole narrowing, silver wiring present, hemorrhages, soft and hard exudates, disappearance of the vein under the arteriole, disk normal</li><li>Grade IV: arterioles are fine fibrous cords; same as grade III except papilledema is present</li> </ul></div></html>
<<tag [[01 Cell Injury]]>>
<<tag [[02 Inflammation and Repair]]>>
<<tag [[03 Immunopathology]]>>
<<tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]]>>
<<tag [[05 Genetic and Developmental Disorders]]>>
<<tag [[06 Environmental Pathology]]>>
<<tag [[07 Nutritional Disorders]]>>
<<tag [[08 Neoplasia]]>>
<<tag [[09 Vascular Disorders]]>>
<<tag [[10 Heart Disorders]]>>
<<tag [[11 Red Blood Cell Disorders]]>>
<<tag [[12 White Blood Cell Disorders]]>>
<<tag [[13 Lymphoid Tissue Disorders]]>>
<<tag [[14 Hemostasis Disorders]]>>
<<tag [[15 Immunohematology Disorders]]>>
<<tag [[16 Upper and Lower Respiratory Disorders]]>>
<<tag [[17 Gastrointestinal Disorders]]>>
<<tag [[18 Hepatobiliary and Pancreatic Disorders]]>>
<<tag [[19 Kidney Disorders]]>>
<<tag [[20 Lower Urinary Tract and Male Reproductive Disorders]]>>
<<tag [[21 Female Reproductive Disorders and Breast Disorders]]>>
<<tag [[22 Endocrine Disorders]]>>
<<tag [[23 Musculoskeletal and Soft Tissue Disorders]]>>
<<tag [[24 Skin Disorders]]>>
<<tag [[25 Nervous System and Special Sensory Disorders]]>>
/***
|Name:|CloseOnCancel+Plugin|
|Description:|Closes the tiddler if you click new tiddler then cancel. Default behaviour is to leave it open.|
|@@modified@@|@@AXS,03/2011: the original plugin closes the tiddler whether you click cancel OR ok on the confirm dialog. This version closes on cancel only if the @@|
|Version:|3.0.1 ($Rev: 3861 $)|
|Date:|$Date: 2008-03-08 10:53:09 +1000 (Sat, 08 Mar 2008) $|
|Source:|http://mptw.tiddlyspot.com/#CloseOnCancelPlugin|
|Author:|Simon Baird <simon.baird@gmail.com>|
|License:|http://mptw.tiddlyspot.com/#TheBSDLicense|
***/
//{{{
merge(config.commands.cancelTiddler,{
handler_mptw_orig_closeUnsaved: config.commands.cancelTiddler.handler,
handler: function(event,src,title) {
this.handler_mptw_orig_closeUnsaved(event,src,title);
if (!store.tiddlerExists(title)){
//if we're here then it's a new tiddler (not checking for shadow tiddlers
if(!story.isDirty(title)){
//if we're here, the user pressed 'ok' in the confirm dialog in the previous handler
story.closeTiddler(title,true);
}
}
return false;
}
});
//}}}
/***
|Name|CollapseTiddlersPlugin|
|Source|http://www.TiddlyTools.com/#CollapseTiddlersPlugin|
|Version|2.0.0|
|Author|Eric Shulman|
|OriginalAuthor|Bradley Meck - http://gensoft.revhost.net/Collapse.html|
|License|unknown|
|~CoreVersion|2.1|
|Type|plugin|
|Requires|CollapsedTemplate|
|Description|show/hide content of a tiddler while leaving tiddler title visible|
This plugin provides commands to quickly switch a rendered tiddler between its current ViewTemplate display and a minimal display (title and toolbar) defined by a separate CollapsedTemplate.
!!!Usage
<<<
In [[ToolbarCommands::ViewToolbar|ToolbarCommands]], add:
{{{
collapseTiddler collapseOthers
}}}
you can also embed the following macros in tiddler content:
*{{{<<collapseAll>>}}} - adds 'collapse all' command that applies CollapsedTemplate to each displayed tiddler
*{{{<<expandAll>>}}} - adds 'expand all' command that re-applies ViewTemplate (or equivalent custom template) to each displayed tiddler
*{{{<<foldFirst>>}}} - immediately apply CollapsedTemplate to a given tiddler, as soon as it is displayed.
<<<
!!!Revisions
<<<
2009.05.04 [2.0.0] standardized documentation and added version #
2008.10.05 collapseAll() and expandAll(): added "return false" to button handlers to prevent IE page transition
2008.03.06 refactored all code for size reduction, readability, and I18N/L10N-readiness. Also added 'folded' flag to tiddler elements (for use by other plugins that need to know if tiddler is folded (e.g., [[SinglePageModePlugin]]
2007.10.11 moved [[FoldFirst]] inline script and converted to {{{<<foldFirst>>}}} macro
2007.12.09 suspend/resume SinglePageMode (SPM/TPM/BPM) when folding/unfolding tiddlers
2007.05.06 add "return false" at the end of each command handler to prevent IE 'page transition' problem.
2007.03.30 add a shadow definition for CollapsedTemplate. Tweak ViewTemplate shadow so "fold/unfold" and "focus" toolbar items automatically appear when using default templates. Remove error check for "CollapsedTemplate" existence, since shadow version will now always work as a fallback.
2006.02.24 added fallback to "CollapsedTemplate" if "WebCollapsedTemplate" is not found
2006.02.06 added check for 'readOnly' flag to use alternative "WebCollapsedTemplate"
<<<
!!!Code
***/
//{{{
version.extensions.CollapseTiddlersPlugin= {major: 2, minor: 0, revision: 0, date: new Date(2009,5,4)};
config.shadowTiddlers.CollapsedTemplate=
"<!--{{{-->\
<div class='toolbar' macro='toolbar expandTiddler collapseOthers closeTiddler closeOthers +editTiddler permalink references jump'></div>\
<div class='title' macro='view title'></div>\
<!--}}}-->";
// automatically tweak shadow ViewTemplate to add "collapseTiddler collapseOthers" commands
config.shadowTiddlers.ViewTemplate=config.shadowTiddlers.ViewTemplate.replace(/closeTiddler/,"collapseTiddler collapseOthers closeTiddler");
config.commands.collapseTiddler = {
text: "fold",
tooltip: "Collapse this tiddler",
collapsedTemplate: "CollapsedTemplate",
webCollapsedTemplate: "WebCollapsedTemplate",
handler: function(event,src,title) {
var e = story.findContainingTiddler(src); if (!e) return false;
// don't fold tiddlers that are being edited!
if(story.isDirty(e.getAttribute("tiddler"))) return false;
var t=config.commands.collapseTiddler.getCollapsedTemplate();
config.commands.collapseTiddler.saveTemplate(e);
config.commands.collapseTiddler.display(title,t);
e.setAttribute("folded","true");
return false;
},
getCollapsedTemplate: function() {
if (readOnly&&store.tiddlerExists(this.webCollapsedTemplate))
return this.webCollapsedTemplate;
else
return this.collapsedTemplate
},
saveTemplate: function(e) {
if (e.getAttribute("savedTemplate")==undefined)
e.setAttribute("savedTemplate",e.getAttribute("template"));
},
// fold/unfold tiddler with suspend/resume of single/top/bottom-of-page mode
display: function(title,t) {
var opt=config.options;
var saveSPM=opt.chkSinglePageMode; opt.chkSinglePageMode=false;
var saveTPM=opt.chkTopOfPageMode; opt.chkTopOfPageMode=false;
var saveBPM=opt.chkBottomOfPageMode; opt.chkBottomOfPageMode=false;
story.displayTiddler(null,title,t);
opt.chkBottomOfPageMode=saveBPM;
opt.chkTopOfPageMode=saveTPM;
opt.chkSinglePageMode=saveSPM;
}
}
config.commands.expandTiddler = {
text: "unfold",
tooltip: "Expand this tiddler",
handler: function(event,src,title) {
var e = story.findContainingTiddler(src); if (!e) return false;
var t = e.getAttribute("savedTemplate");
config.commands.collapseTiddler.display(title,t);
e.setAttribute("folded","false");
return false;
}
}
config.macros.collapseAll = {
text: "collapse all",
tooltip: "Collapse all tiddlers",
handler: function(place,macroName,params,wikifier,paramString,tiddler){
createTiddlyButton(place,this.text,this.tooltip,function(){
story.forEachTiddler(function(title,tiddler){
if(story.isDirty(title)) return;
var t=config.commands.collapseTiddler.getCollapsedTemplate();
config.commands.collapseTiddler.saveTemplate(tiddler);
config.commands.collapseTiddler.display(title,t);
tiddler.folded=true;
});
return false;
})
}
}
config.macros.expandAll = {
text: "expand all",
tooltip: "Expand all tiddlers",
handler: function(place,macroName,params,wikifier,paramString,tiddler){
createTiddlyButton(place,this.text,this.tooltip,function(){
story.forEachTiddler(function(title,tiddler){
var t=config.commands.collapseTiddler.getCollapsedTemplate();
if(tiddler.getAttribute("template")!=t) return; // re-display only if collapsed
var t=tiddler.getAttribute("savedTemplate");
config.commands.collapseTiddler.display(title,t);
tiddler.folded=false;
});
return false;
})
}
}
config.macros.collapseOthers = {
text: "focus",
tooltip: "Expand this tiddler and collapse all others",
handler: function(place,macroName,params,wikifier,paramString,tiddler) {
var e = story.findContainingTiddler(place); if (!e) return false;
story.forEachTiddler(function(title,tiddler) {
if(story.isDirty(title)) return;
var t=config.commands.collapseTiddler.getCollapsedTemplate();
if (e==tiddler) t=e.getAttribute("savedTemplate");
config.commands.collapseTiddler.saveTemplate(tiddler);
config.commands.collapseTiddler.display(title,t);
tiddler.folded=(e!=tiddler);
})
return false;
}
}
config.commands.collapseOthers = {
text: "focus",
tooltip: "Expand this tiddler and collapse all others",
handler: function(event,src,title) {
var e = story.findContainingTiddler(src); if (!e) return false;
story.forEachTiddler(function(title,tiddler) {
if(story.isDirty(title)) return;
var t=config.commands.collapseTiddler.getCollapsedTemplate();
if (e==tiddler) t=e.getAttribute("savedTemplate");
config.commands.collapseTiddler.saveTemplate(tiddler);
config.commands.collapseTiddler.display(title,t);
tiddler.folded=(e!=tiddler);
})
return false;
}
}
// {{{<<foldFirst>>}}} macro forces tiddler to be folded when *initially* displayed.
// Subsequent re-render does NOT re-fold tiddler, but closing/re-opening tiddler DOES cause it to fold first again.
config.macros.foldFirst = {
handler: function(place,macroName,params,wikifier,paramString,tiddler){
var e=story.findContainingTiddler(place);
if (e.getAttribute("foldedFirst")=="true") return; // already been folded once
var title=e.getAttribute("tiddler")
var t=config.commands.collapseTiddler.getCollapsedTemplate();
config.commands.collapseTiddler.saveTemplate(e);
config.commands.collapseTiddler.display(title,t);
e.setAttribute("folded","true");
e.setAttribute("foldedFirst","true"); // only when tiddler is first rendered
return false;
}
}
//}}}
<!--{{{-->
<!--
|Name|CollapsedTemplate|
|Source|http://www.TiddlyTools.com/#CollapsedTemplate|
|Version||
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|template|
|Requires|ToolbarCommands|
|Description|alternative to ViewTemplate, used by CollapseTiddlersPlugin to display tiddler when 'folded'|
-->
<span class='title' macro='view title'></span>
<span style="float:right;" class='toolbar' macro='toolbar [[ToolbarCommands::CollapsedToolbar]]'></span>
<div class='tagClear'></div>
<!--}}}-->
Background: #fff
Foreground: #000
PrimaryPale: #8cf
PrimaryLight: #18f
PrimaryMid: #04b
PrimaryDark: #014
SecondaryPale: #ffc
SecondaryLight: #fe8
SecondaryMid: #db4
SecondaryDark: #841
TertiaryPale: #eee
TertiaryLight: #ccc
TertiaryMid: #999
TertiaryDark: #666
Error: #f88
<<paletteView [[ColorPalette]]>>
/***
|Name|CommentPluginInfo|
|Source|http://www.TiddlyTools.com/#CommentPlugin|
|Documentation|http://www.TiddlyTools.com/#CommentPluginInfo|
|Version|2.9.3|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|Documentation|
|Description|Documentation for CommentPlugin|
!!!!!Usage
<<<
syntax:
{{{
<<comment TiddlerName overwrite reverse marker:... tags format dateformat>>
}}}
where:
*''~TiddlerName'' //(optional)//<br>specifies the 'target' tiddler into which comments will be written. If you use the keyword, //{{{"here"}}}// (or omit all parameters), the current tiddler is used by default. The ~TiddlerName can also include special //substitution markers// to construct a unique target title by dynamically inserting values, where:
**%tiddler%=containing tiddler title,
**%UTC%=UTC timestamp (YYYYMMMDD.HHMMSSMMM),
**%random%=random decimal number (.123456789),
**%who%=current TiddlyWiki username,
**%subject%=comment subject text.
*''overwrite'' //(optional)//<br>Normally, comments are //added// to a target tiddler if it already exists. However, if you use the ''overwrite'' keyword, the new comment text //''completely replaces the previous contents of an existing tiddler''//.
*''reverse'' //(optional)//<br>By default, new comments are added to the target tiddler //following// any existing comments. When ''reverse'' is used, new comments are inserted //before// existing comments, resulting in a reverse-chronological display (i.e, newest comments shown first).
*''marker:...'' //(optional)//<br>specifies an alternative //substitution marker// within the target tiddler (see below).
*''tags'' //(optional)//<br>adds specified space-separated tags to the target tiddler whenever a comment is written. Note that the list of tags should be enclosed in "..." so that it is processed as a single parameter.
*''format'' //(optional)//<br>specifies a custom output format that overrides the default format defined in {{{config.macros.comment.fmt}}} (see Configuration, below), using the following //substitution markers//:
**%tiddler%=containing tiddler title,
**%UTC%=UTC timestamp (YYYYMMMDD.HHMMSSMMM),
**%when%=formatted date/time,
**%who%=username,
**%subject%=subject,
**%message%=comment body text.
*''dateformat'' //(optional)//<br>specifies a custom date/timestamp output to be inserted in place of {{{%when%}} in the comment output format above. Overrides the default format defined in {{{config.macros.comment.datefmt}}} (see Configuration, below).
To indicate the location within the target tiddler where new comments are to be inserted, embed {{{/%comment%/}}} as a //substitution marker// //within that target tiddler's source//. Each new comment is inserted immediately preceding the marker, resulting in a time-ordered sequence of comments. If no marker is present, new comments are appended to the end of the tiddler. To insert comments from different forms into separate locations in the //same target tiddler//, you can use the ''marker:...'' parameter to specify alternative marker text (e.g., use "marker:note" or "marker:memo" to specify {{{/%note%/}}} or {{{/%memo%/}}} instead of {{{/%comment%/}}})
<<<
!!!!!Configuration
<<<
To configure the behavior and formats used by [[CommentPlugin]], //''place one or more of the following javascript statements in a tiddler tagged with<<tag systemConfig>>''//: //(note: the default values for each setting are shown)//
{{{
config.macros.comment.reverse=false;
}}}
>when set to {{{true}}}, all new comments are inserted //following// the comment marker instead of preceding it, resulting in a reverse chronological display order. If no comment marker is present in the target tiddler source, the 'reverse' option is ignored and new comments are always appended to the end of the tiddler.
{{{
config.macros.comment.fmt="__''%subject%''__\n^^posted by %who% on %when%^^\n<<<\n%message%\n<<<\n";
}}}
>defines the comment output format to be inserted into the tiddler, where: %when%=date/time, %who%=username, %subject%=subject, and %message% is the body of the comment. //Note: if you omit %subject% from the output format, the subject input field on the comment form will be automatically suppressed. Similarly, omitting %message% from the output format suppresses the message input field. This can be useful when using the {{{<<comment>>}}} macro to create simple activity logs that only require a short, one-line subject rather than entering extended message content.//
{{{
config.macros.comment.datefmt="DDD, MMM DDth, YYYY at hh12:0mm:0ss am";
}}}
>defines the date/timestamp output used within the comment format above.
{{{
config.macros.comment.tags="";
}}}
>defines an optional space-separated, list of tags to be added to the target tiddler whenever a comment is written. This is most useful when the target tiddler is different from the tiddler containing the {{{<<comment>>}}} macro, to make it easy to locate that tiddler later on.
Note: as of revision 2.0.0, direct dependency on [[NestedSlidersPlugin]], [[MoveablePanelPlugin]], [[InlineJavascriptPlugin]] and [[ToggleSliders]] has been eliminated. As a result, the comment form and generated comment output are no longer automatically contained within sliders and the "view all/close all" command is not automatically included. To recreate the previous output format and comment interface, use the following syntax in the tiddler in which you want to place your comments:
{{{
+++^40em^[add a note]...
<<moveablePanel>>add a note
----
<<comment here "" "+++!!!!![%when% (%who%): %subject%]>...\n%message%\n===\n">>===
| <<tiddler ToggleSliders with: here "view all" "close all">>
}}}
<<<
!!!!!Revisions
<<<
2009.04.10 2.9.3 invoke autoSaveChanges() after adding a comment
2009.03.09 2.9.2 added marker:... macro parameter
2009.03.08 2.9.1 fix handling of nosubject/nomessage when macro param specifies output format
2008.05.17 2.9.0 optional 'overwrite' param replaces existing comment when stored as separate tiddler
2008.04.21 2.8.0 replaced use of %n markers with special 'named' markers: %tiddler%, %UTC%, %random%, %who%, %when%, %subject% and %message% to avoid conflict with TW core processing of tiddler content. Also, added support for 'reverse' macro param.
2008.04.17 2.7.0 added support for constructing target by inserting UTC timestamp, random number, username and/or subject text into target tiddler title
2008.04.15 2.6.0 added support for custom format and dateformat parameters to override global default formats
2008.04.15 2.5.1 make sure tiddlers are displayed before attempting to refresh them
2008.04.15 2.5.0 refresh tiddler containing comment macro after adding new comment to target tiddler (if different)
2008.04.14 2.4.0 added optional tag list parameter for tagging the target tiddler when comments are written
2008.04.14 2.3.0 if %2 (subject) or %3 (message) are omitted from format string, suppress display and validation of corresponding form elements.
2008.04.13 2.2.0 added optional ~TiddlerName param to specify target tiddler for writing comments
2008.04.10 2.1.0 converted from inline script to plugin
2008.04.05 2.0.0 removed dependencies on NestedSlidersPlugin, MoveablePanelPlugin, ToggleSliders
2007.10.24 1.2.0 added config.options.txtCommentDateFormat
2007.07.05 1.1.0 added 'view all/close all' toolbar item plus code cleanup
2007.06.28 1.0.2 added tiddler.fields to saveTiddler() call (preserves custom fields)
2007.05.26 1.0.1 added support for optional 'reverse' keyword.
2006.04.20 1.0.0 initial release
<<<
<<tiddler Chapters>>
<<tag TABLE Tables>>
<<tag BOX Boxes>>
<<tag FIGURE Figures>>
/***
|Name|DisableWikiLinksPlugin|
|Source|http://www.TiddlyTools.com/#DisableWikiLinksPlugin|
|Version|1.6.0|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|selectively disable TiddlyWiki's automatic ~WikiWord linking behavior|
This plugin allows you to disable TiddlyWiki's automatic ~WikiWord linking behavior, so that WikiWords embedded in tiddler content will be rendered as regular text, instead of being automatically converted to tiddler links. To create a tiddler link when automatic linking is disabled, you must enclose the link text within {{{[[...]]}}}.
!!!!!Usage
<<<
You can block automatic WikiWord linking behavior for any specific tiddler by ''tagging it with<<tag excludeWikiWords>>'' (see configuration below) or, check a plugin option to disable automatic WikiWord links to non-existing tiddler titles, while still linking WikiWords that correspond to existing tiddlers titles or shadow tiddler titles. You can also block specific selected WikiWords from being automatically linked by listing them in [[DisableWikiLinksList]] (see configuration below), separated by whitespace. This tiddler is optional and, when present, causes the listed words to always be excluded, even if automatic linking of other WikiWords is being permitted.
Note: WikiWords contained in default ''shadow'' tiddlers will be automatically linked unless you select an additional checkbox option lets you disable these automatic links as well, though this is not recommended, since it can make it more difficult to access some TiddlyWiki standard default content (such as AdvancedOptions or SideBarTabs)
<<<
!!!!!Configuration
<<<
<<option chkDisableWikiLinks>> Disable ALL automatic WikiWord tiddler links
<<option chkAllowLinksFromShadowTiddlers>> ... except for WikiWords //contained in// shadow tiddlers
<<option chkDisableNonExistingWikiLinks>> Disable automatic WikiWord links for non-existing tiddlers
Disable automatic WikiWord links for words listed in: <<option txtDisableWikiLinksList>>
Disable automatic WikiWord links for tiddlers tagged with: <<option txtDisableWikiLinksTag>>
<<<
!!!!!Revisions
<<<
2008.07.22 [1.6.0] hijack tiddler changed() method to filter disabled wiki words from internal links[] array (so they won't appear in the missing tiddlers list)
2007.06.09 [1.5.0] added configurable txtDisableWikiLinksTag (default value: "excludeWikiWords") to allows selective disabling of automatic WikiWord links for any tiddler tagged with that value.
2006.12.31 [1.4.0] in formatter, test for chkDisableNonExistingWikiLinks
2006.12.09 [1.3.0] in formatter, test for excluded wiki words specified in DisableWikiLinksList
2006.12.09 [1.2.2] fix logic in autoLinkWikiWords() (was allowing links TO shadow tiddlers, even when chkDisableWikiLinks is TRUE).
2006.12.09 [1.2.1] revised logic for handling links in shadow content
2006.12.08 [1.2.0] added hijack of Tiddler.prototype.autoLinkWikiWords so regular (non-bracketed) WikiWords won't be added to the missing list
2006.05.24 [1.1.0] added option to NOT bypass automatic wikiword links when displaying default shadow content (default is to auto-link shadow content)
2006.02.05 [1.0.1] wrapped wikifier hijack in init function to eliminate globals and avoid FireFox 1.5.0.1 crash bug when referencing globals
2005.12.09 [1.0.0] initial release
<<<
!!!!!Code
***/
//{{{
version.extensions.DisableWikiLinksPlugin= {major: 1, minor: 6, revision: 0, date: new Date(2008,7,22)};
if (config.options.chkDisableNonExistingWikiLinks==undefined) config.options.chkDisableNonExistingWikiLinks= false;
if (config.options.chkDisableWikiLinks==undefined) config.options.chkDisableWikiLinks=false;
if (config.options.txtDisableWikiLinksList==undefined) config.options.txtDisableWikiLinksList="DisableWikiLinksList";
if (config.options.chkAllowLinksFromShadowTiddlers==undefined) config.options.chkAllowLinksFromShadowTiddlers=true;
if (config.options.txtDisableWikiLinksTag==undefined) config.options.txtDisableWikiLinksTag="excludeWikiWords";
// find the formatter for wikiLink and replace handler with 'pass-thru' rendering
initDisableWikiLinksFormatter();
function initDisableWikiLinksFormatter() {
for (var i=0; i<config.formatters.length && config.formatters[i].name!="wikiLink"; i++);
config.formatters[i].coreHandler=config.formatters[i].handler;
config.formatters[i].handler=function(w) {
// supress any leading "~" (if present)
var skip=(w.matchText.substr(0,1)==config.textPrimitives.unWikiLink)?1:0;
var title=w.matchText.substr(skip);
var exists=store.tiddlerExists(title);
var inShadow=w.tiddler && store.isShadowTiddler(w.tiddler.title);
// check for excluded Tiddler
if (w.tiddler && w.tiddler.isTagged(config.options.txtDisableWikiLinksTag))
{ w.outputText(w.output,w.matchStart+skip,w.nextMatch); return; }
// check for specific excluded wiki words
var t=store.getTiddlerText(config.options.txtDisableWikiLinksList);
if (t && t.length && t.indexOf(w.matchText)!=-1)
{ w.outputText(w.output,w.matchStart+skip,w.nextMatch); return; }
// if not disabling links from shadows (default setting)
if (config.options.chkAllowLinksFromShadowTiddlers && inShadow)
return this.coreHandler(w);
// check for non-existing non-shadow tiddler
if (config.options.chkDisableNonExistingWikiLinks && !exists)
{ w.outputText(w.output,w.matchStart+skip,w.nextMatch); return; }
// if not enabled, just do standard WikiWord link formatting
if (!config.options.chkDisableWikiLinks)
return this.coreHandler(w);
// just return text without linking
w.outputText(w.output,w.matchStart+skip,w.nextMatch)
}
}
Tiddler.prototype.coreAutoLinkWikiWords = Tiddler.prototype.autoLinkWikiWords;
Tiddler.prototype.autoLinkWikiWords = function()
{
// if all automatic links are not disabled, just return results from core function
if (!config.options.chkDisableWikiLinks)
return this.coreAutoLinkWikiWords.apply(this,arguments);
return false;
}
Tiddler.prototype.disableWikiLinks_changed = Tiddler.prototype.changed;
Tiddler.prototype.changed = function()
{
this.disableWikiLinks_changed.apply(this,arguments);
// remove excluded wiki words from links array
var t=store.getTiddlerText(config.options.txtDisableWikiLinksList,"").readBracketedList();
if (t.length) for (var i=0; i<t.length; i++)
if (this.links.contains(t[i]))
this.links.splice(this.links.indexOf(t[i]),1);
};
//}}}
/***
|Name|DiscussionPluginInfo|
|Source|http://www.TiddlyTools.com/#DiscussionPlugin|
|Documentation|http://www.TiddlyTools.com/#DiscussionPluginInfo|
|Version|1.5.7|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|Documentation|
|Description|Documentation for DiscussionPlugin|
!!!!!Usage
<<<
syntax:
{{{
<<discussion listformat reverse tags commentformat dateformat>>
}}}
where:
*''listformat'' //(optional)//<br>specifies the display format for each item in the summary list. //Note: when specifying additional macro parameters, you can use a blank value (e.g., {{{""}}}) as a 'placeholder' to allow the default item format to be used.//
*''reverse'' //(optional)//<br>by default, the comments in the discussion summary list are shown in date/time order, with the oldest item listed first. The ''reverse'' keyword, when present, indicates the display order should be inverted so that the most recent item is listed first.
*''tags'' //(optional)//<br>specifies one or more space-separated tags to add to the target tiddler whenever a comment is written. Note that the list of tags should be enclosed in "..." so that it is processed as a single parameter. If you do not want tags added to the individual comment tiddlers, use a blank value (e.g., {{{""}}}) as a 'placeholder'. Regardless of the tags that are specified, a tag of "comment" is always added to each target tiddler. This is required in order to locate the tiddler when generating the dicussion summary list.
*''commentformat'' //(optional)//<br>specifies a custom output format to be used when inserting comments into the target tiddler, where: %when%=formatted date/timestamp, %who%=username, %subject%=comment subject text, and %message% is the body of the comment. When present, this parameter overrides the default output format defined via {{{config.macros.comment.fmt}}}. See the ''Configuration'' section below and in [[CommentPluginInfo]] for additional details.
*''dateformat'' //(optional)//<br>specifies a custom date/timestamp output used within the comment format above. When present, this parameter overrides the default date/timestamp format defined via {{{config.macros.comment.datefmt}}}. See the ''Configuration'' section below and in [[CommentPluginInfo]] for additional details.
<<<
!!!!!Configuration
<<<
[[DiscussionPlugin]] can automatically modify the default shadow [[ViewTemplate]] so that all tiddlers will be rendered with two tabs: "Page", and "Discussion". The "Page" tab displays the regular tiddler content, while the "Discussion" tab displays the summary list of comments as well as an input form to enter new comments. You can enable/disable this action by setting/clearing the following checkbox:
><<option chkDiscussionTemplate>> Automatically modify default shadow [[ViewTemplate]]
>usage: {{{<<option chkDiscussionTemplate>>}}}
>^^(or place {{{config.options.chkDiscussionTemplate=true;}}} in a tiddler tagged with "systemConfig")^^
Note: //''You must reload your document for changes to this option to take effect.''// In addition, this option is only applied to the shadow [[ViewTemplate]]. If you are using a custom [[ViewTemplate]], you will need to manually alter that template to add the Page and Discussion tab display (see below)
<<<
!!!!!Using tags to add discussion tabs to individual tiddlers
<<<
When your document is loaded, DiscussionPlugin automatically creates a shadow DiscussionViewTemplate that is copy of the current ViewTemplate, with the discussion tab syntax automatically installed. If TiddlyTools' TaggedTemplateTweak is also installed in your document then, rather than using the checkbox option to add discussion tabs to //every// tiddler in your document, you can selectively tag individual tiddlers with "discussion" to add the discussion tabs to only those specific tiddlers.
Conversely, if you enable the checkbox option to modify the default ViewTemplate, you can selectively tag individual tiddlers with "noDiscussion" to apply a shadow NoDiscussionViewTemplate that will use an unmodified version of the current ViewTemplate, thereby preventing the discussion tabs from appearing on those specific tiddlers.
<<<
!!!!!Using a customized [[ViewTemplate]]
<<<
To enable the discussion tab display when using a custom [[ViewTemplate]], you should edit that template and change this line:
{{{
<div class='viewer' macro='view text wikified'></div>
}}}
to:
{{{
<div class='viewer' macro='tabs txtDiscussionTab
Page Page CurrentTiddler Discussion Discussion DiscussionTiddler'></div>
}}}
>[[CurrentTiddler]] and [[DiscussionTiddler]] are special shadow tiddlers defined by the plugin. [[CurrentTiddler]] enables the {{{<<tabs>>}}} macro used in the [[ViewTemplate]] to display the content for the current tiddler within a tab, while [[DiscussionTiddler]] simply invokes the default {{{<<discussion>>}}} macro without any extra parameters in order to render the corresponding discussion summary list and comment input form. You can modify the these shadow definitions to add macro parameters or other custom content that will automatically appear in the discussion tab when each tiddler is rendered.
Note: if you are using a custom [[ViewTemplate]], you should also manually create custom versions of DiscussionViewTemplate and NoDiscussionViewTemplate as well, so that you can use the tagging method described above to selectively display discussion tabs for tiddlers that also apply your custom-defined templates.
<<<
!!!!!Plugin customization settings
<<<
To configure the global defaults used by [[DiscussionPlugin]], you can place one or more of the following javascript statements in a tiddler tagged with <<tag systemConfig>>: //(note: the default values for each setting are shown)//
{{{
config.macros.discussion.listfmt="#<<slider [[]] [[%tiddler%]] [[%subject%]] [[posted by %who% on %when%]]>>\n";
}}}
>defines the output format for each item in the discussion summary list, where: %tiddler%=tiddler title of the individual comment tiddler, %subject%=subject text, %who%=username, and %when% is the formatted date/time of the comment. These values are automatically stored in each comment tiddler by using a //hidden slice table//, so that this information can be easily retrieved when generating the summary list output.
{{{
config.macros.discussion.reverse=false;
}}}
>when set to {{{true}}}, the discussion summary list is displayed in a reverse chronological order.
{{{
config.macros.discussion.titlefmt="_%UTC%%random%";
}}}
>When comments are entered, they are written into separate target tiddlers whose titles are constructed by appending a generated suffix to the title of the tiddler containing the {{{<<discussion>>}}} macro. By default, this suffix contains the current UTC timestamp (e.g., YYYYMMDD.HHMMSSMMM) plus a randomly generated number (e.g., .123456789) to ensure that all target tiddlers have unique titles while also associating each comment with the specific discussion summary. The suffix is specified by using //substitution markers//, where: %UTC%=the UTC timestamp, %random%=a random decimal number, %who%=username, and %subject% is the subject text entered into the comment form.
{{{
config.macros.discussion.tags="comment excludeLists";
}}}
>Target tiddlers are automatically tagged with "comment" so that the {{{<<discussion>>}}} macro can locate them when generating the summary list. To reduce 'information clutter', target tiddlers are also tagged with "excludeLists" so that they don't automatically appear in the list of tiddlers shown in the sidebar tabs. You can use this setting to specify an optional space-separated list of tags to be added to the target tiddler whenever a comment is written. You can use a blank value (e.g., {{{""}}} if you do not want to add any extra tags to the target tiddler. However, as noted above, regardless of the specified tags, target tiddlers will still be tagged with "comment" in order to ensure that the {{{<<discussion>>}}} macro includes them in the summary list.
{{{
config.macros.discussion.commentfmt="^^posted by %who% on %when%^^\n<<<\n%message%\n<<<\n";
}}}
>defines the comment output format to be inserted into the target tiddler, where: %when%=date/timestamp, %who%=username, %subject%=subject, and %message% is the body of the comment. //Note: if you omit %subject% from the output format, the subject input field on the comment form will be automatically suppressed. Similarly, omitting %message% from the output format suppresses the message input field. This can be useful when using the {{{<<comment>>}}} macro to create simple activity logs that only require a short, one-line subject rather than entering extended message content.//
{{{
config.macros.comment.datefmt="DDD, MMM DDth, YYYY at hh12:0mm:0ss am";
}}}
>defines the date/timestamp output used within the comment format above.
<<<
!!!!!Revisions
<<<
2009.01.04 1.5.7 in customized ViewTemplate, corrected 'tabs' macro to avoid error when viewing shadow tiddlers
2008.10.31 1.5.6 added optional 'after' param to countComments() so 'new postings' count can be displayed (using customized DiscussionViewTemplate
2008.10.30 1.5.5 added comment count to discussion tab. See countComments() function.
2008.05.15 1.5.0 added automatic creation of shadows for DiscussionViewTemplate and NoDiscussionViewTemplate
2008.04.21 1.4.0 replaced use of %n markers with special 'named' markers: %tiddler%, %UTC%, %random%, %who%, %when%, %subject% and %message% to avoid conflict with TW core processing of tiddler content.
2008.04.17 1.3.0 added ability to customize generated 'comment tiddler' titles by using substitution parameters.
2008.04.17 1.2.0 added ability to customize generated 'comment tiddler' titles by using substitution parameters.
2008.04.15 1.1.1 in currentTiddler.handler(), prevent infinite recursion by removing {{{<<currentTiddler>>}}} from content being wikified.
2008.04.15 1.1.0 added parameters for reverse, listformat, tags, commentformat, dateformat
2008.04.14 1.0.0 initial prototype
<<<
/***
|!''Name:''|!''E''asily ''A''daptable ''S''ource ''E''ditor|
|''Description:''|this framework allows you to easily create commands that work on the current tiddler text selection in edit mode|
|''Version:''|0.1.0|
|''Date:''|13/01/2007|
|''Source:''|http://yann.perrin.googlepages.com/twkd.html#E.A.S.E|
|''Author:''|[[Yann Perrin|YannPerrin]]|
|''License:''|[[BSD open source license]]|
|''~CoreVersion:''|2.x|
|''Browser:''|Firefox 1.0.4+; Firefox 1.5; InternetExplorer 6.0|
***/
////Messages Definition
//{{{
config.messages.Ease = {
noselection:"nothing selected",
asktitle:"enter the new tiddler title",
exists:" already exists, please enter another title",
askForTagsLabel:"enter the new tiddler tags",
tiddlercreated:" tiddler created"
}
//}}}
////
//{{{
if (!window.TWkd) window.TWkd={context:{}};
if (!TWkd.Ease)
TWkd.Ease = function (text,tooltip){
this.text = text;
this.tooltip = tooltip;
this.modes = [];
this.addMode = function(modeDefinition) {this.modes.push(modeDefinition);};
this.handler = function(event,src,title) {
TWkd.context.command = this;
TWkd.context.selection=this.getSelection(title);
if (this.modes.length==1) {
this.modes[0].operation();
}
else {
var popup = Popup.create(src);
if(popup) {
for (var i=0; i<this.modes.length; i++) {
createTiddlyButton(createTiddlyElement(popup,"li"), this.modes[i].name, this.modes[i].tooltip, this.OperateFromButton, null, 'id'+i, null);
}
Popup.show(popup,false);
event.cancelBubble = true;
if (event.stopPropagation) event.stopPropagation();
return false;
}
}
};
};
TWkd.Ease.prototype.OperateFromButton = function(e){
var commandMode=this.getAttribute('Id').replace('id','');
TWkd.context.command.modes[commandMode].operation();
};
TWkd.Ease.prototype.getTiddlerEditField = function(title,field){
/*var tiddler = document.getElementById(story.idPrefix + title);
if(tiddler != null){
var children = tiddler.getElementsByTagName("*")
var e = null;
for (var t=0; t<children.length; t++){
var c = children[t];
if(c.tagName.toLowerCase() == "input" || c.tagName.toLowerCase() == "textarea"){
if(!e) {e = c;}
if(c.getAttribute("edit") == field){e = c;}
}
}
if(e){return e;}
}
*/
return jQuery('.editor').eq(1).find('iframe').contents().find('#xEditingArea>iframe').contents().find('body');
} // closes getTiddlerEditField function definition
TWkd.Ease.prototype.getSelection = function(title,quiet) {
var tiddlerTextArea = this.getTiddlerEditField(title,"text");
var result = {};
if (document.selection != null && tiddlerTextArea.selectionStart == null) {
tiddlerTextArea.focus();
var range = document.selection.createRange();
var bookmark = range.getBookmark();
var contents = tiddlerTextArea.value;
var originalContents = contents;
var marker = "##SELECTION_MARKER_" + Math.random() + "##";
while(contents.indexOf(marker) != -1) {
marker = "##SELECTION_MARKER_" + Math.random() + "##";
}
var selection = range.text;
range.text = marker + range.text + marker;
contents = tiddlerTextArea.value;
result.start = contents.indexOf(marker);
contents = contents.replace(marker, "");
result.end = contents.indexOf(marker);
tiddlerTextArea.value = originalContents;
range.moveToBookmark(bookmark);
range.select();
}
else {
result.start=tiddlerTextArea.selectionStart;
result.end=tiddlerTextArea.selectionEnd;
}
result.content=tiddlerTextArea.value.substring(result.start,result.end);
result.source=title;
if (!result.content&&!quiet) displayMessage(config.messages.Ease.noselection);
return(result);
}//closes getSelection function definition
// replace selection or insert new content
TWkd.Ease.prototype.putInPlace=function(content,workplace) {
var tiddlerText = this.getTiddlerEditField(workplace.source,"text");
tiddlerText.value = tiddlerText.value.substring(0,workplace.start)+content+tiddlerText.value.substring(workplace.end);
}
// asking for title
TWkd.Ease.prototype.askForTitle = function(suggestion) {
if (!suggestion)
suggestion = "";
var newtitle;
while (!newtitle||store.tiddlerExists(newtitle))
{
if (store.tiddlerExists(newtitle))
displayMessage(newtitle+config.messages.Ease.exists);
newtitle = prompt(config.messages.Ease.asktitle,suggestion);
if (newtitle==null)
{
displayMessage(config.messages.Ease.titlecancel);
return(false);
}
}
return(newtitle);
}//closes askForTitle function definition
// creation of a new tiddler
TWkd.Ease.prototype.newTWkdLibTiddler = function(title,content,from,askForTags){
var tiddler = new Tiddler();
tiddler.title = title;
tiddler.modifier = config.options.txtUserName;
tiddler.text = content;
(from) ? tiddler.tags = [from] : tiddler.tags=[];
if (askForTags)
tiddler.tags = prompt(config.messages.Ease.askForTagsLabel,'[['+from+']]').readBracketedList();
store.addTiddler(tiddler);
//store.notifyAll();
displayMessage(title+config.messages.Ease.tiddlercreated);
}
if (!TWkd.Mode)
TWkd.Mode = function (name,tooltip,ask,operation) {
this.name = name;
this.tooltip = tooltip;
this.ask = ask;
this.operation = operation;
};
//}}}
/***
|''Name:''|EasyEdit+Plugin|
|''Description:''|Lite and extensible Wysiwyg editor for TiddlyWiki.|
|''Version:''|1.3.3|
|''Date:''|Dec 21,2007|
|''Source:''|http://visualtw.ouvaton.org/VisualTW.html|
|''Author:''|Pascal Collin|
|@@modified@@|AXS,03/2011 for supoort of more browsers|
|''License:''|[[BSD open source license|License]]|
|''~CoreVersion:''|2.1.0|
|''Browser:''|Firefox 2.0; InternetExplorer 6.0|
!Demo
*On the plugin [[homepage|http://visualtw.ouvaton.org/VisualTW.html]], see [[WysiwygDemo]] and use the {{{write}}} button.
!Installation
#import the plugin,
#save and reload,
#use the <<toolbar easyEdit>> button in the tiddler's toolbar (in default ViewTemplate) or add {{{easyEdit}}} command in your own toolbar.
! Useful Addons
*[[HTMLFormattingPlugin|http://www.tiddlytools.com/#HTMLFormattingPlugin]] to embed wiki syntax in html tiddlers.<<br>>//__Tips__ : When this plugin is installed, you can use anchor syntax to link tiddlers in wysiwyg mode (example : #example). Anchors are converted back and from wiki syntax when editing.//
*[[TaggedTemplateTweak|http://www.TiddlyTools.com/#TaggedTemplateTweak]] to use alternative ViewTemplate/EditTemplate for tiddler's tagged with specific tag values.
!Configuration
|Buttons in the toolbar (empty = all).<<br>>//Example : bold,underline,separator,forecolor//<<br>>The buttons will appear in this order.| <<option txtEasyEditorButtons>>|
|EasyEditor default height | <<option txtEasyEditorHeight>>|
|Stylesheet applied to the edited richtext |[[StyleSheet]]|
|Template called by the {{{write}}} button |[[EasyEdit+Template]]|
!How to extend EasyEditor
*To add your own buttons, add some code like the following in a systemConfig tagged tiddler (//use the prompt attribute only if there is a parameter//) :
**{{{EditorToolbar.buttons.heading = {label:"H", toolTip : "Set heading level", prompt: "Enter heading level"};}}}
**{{{EditorToolbar.buttonsList +=",heading";}}}
*To get the list of all possible commands, see the documentation of the [[Gecko built-in rich text editor|http://developer.mozilla.org/en/docs/Midas]] or the [[IE command identifiers|http://msdn2.microsoft.com/en-us/library/ms533049.aspx]].
*To go further in customization, see [[Link button|EasyEditPlugin-LinkButton]] as an example.
!Code
***/
//{{{
var geckoEditor={};
var IEeditor={};
config.options.txtEasyEditorHeight = config.options.txtEasyEditorHeight ? config.options.txtEasyEditorHeight : "500px";
config.options.txtEasyEditorButtons = config.options.txtEasyEditorButtons ? config.options.txtEasyEditorButtons : "";
// TW2.1.x compatibility
config.browser.isGecko = config.browser.isGecko ? config.browser.isGecko : (config.userAgent.indexOf("gecko") != -1);
config.macros.annotations = config.macros.annotations ? config.macros.annotations : {handler : function() {}}
// EASYEDITOR MACRO
config.macros.easyEdit = {
handler : function(place,macroName,params,wikifier,paramString,tiddler) {
var prms = paramString.parseParams(null, null, true);
var field = params[0];
var height = config.options.txtEasyEditorHeight;
var inline=params.contains('inline');
tiddler= getParam(prms, "tiddler") ? store.getTiddler(getParam(prms, "tiddler")) : tiddler;
editor = field ? new easyEditor(tiddler,field,place,height) : null;
},
gather: function(element){
var iframes = element.getElementsByTagName("iframe");
if (iframes.length!=1) return null
var text = "<html>"+iframes[0].contentWindow.document.body.innerHTML+"</html>";
text = config.browser.isGecko ? geckoEditor.postProcessor(text) : (config.browser.isIE ? IEeditor.postProcessor(text) : text);
return text;
}
}
// EASYEDITOR CLASS
function easyEditor(tiddler,field,place,height) {
this.tiddler = tiddler;
this.field = field;
//this.browser = config.browser.isSafari? safariEditor : (config.browser.isGecko ? geckoEditor : (config.browser.isIE ? IEeditor : null));
this.browser = config.browser.isGecko ? geckoEditor : (config.browser.isIE ? IEeditor : null);
this.wrapper = createTiddlyElement(place,"div",null,"easyEditor");
this.wrapper.setAttribute("easyEdit",this.field);
this.iframe = createTiddlyElement(null,"iframe");
this.browser.setupFrame(this.iframe,height,contextualCallback(this,this.onload));
this.wrapper.appendChild(this.iframe);
}
easyEditor.prototype.onload = function(){
this.editor = this.iframe.contentWindow;
this.doc = this.editor.document;
if (!this.browser.isDocReady(this.doc)) return null;
if (!this.tiddler.isReadOnly() && this.doc.designMode.toLowerCase()!="on") {
this.doc.designMode = "on";
if (this.browser.reloadOnDesignMode) return false; // IE fire readystatechange after designMode change
}
var internalCSS = store.getTiddlerText("StyleSheet");
setStylesheet(internalCSS,"StyleSheet",this.doc);
/*
var internalCSS = store.getTiddlerText("EasyEditDocStyleSheet");
setStylesheet(internalCSS,"EasyEditDocStyleSheet",this.doc);
*/
//this.browser.initContent(this.doc,store.getValue(this.tiddler,this.field)); //replaced by following line (AS,03/2011)
this.initContent(this.iframe,store.getValue(this.tiddler,this.field));
var barElement=createTiddlyElement(null,"div",null,"easyEditorToolBar");
this.wrapper.insertBefore(barElement,this.wrapper.firstChild);
this.toolbar = new EditorToolbar(this.doc,barElement,this.editor);
this.browser.plugEvents(this.doc,contextualCallback(this,this.scheduleButtonsRefresh));
this.editor.focus();
}
easyEditor.SimplePreProcessoror = function(text) {
var re = /^<html>(.*)<\/html>$/m;
var htmlValue = re.exec(text);
var value = (htmlValue && (htmlValue.length>0)) ? htmlValue[1] : text;
return value;
}
easyEditor.prototype.scheduleButtonsRefresh=function() { //doesn't refresh buttons state when rough typing
if (this.nextUpdate) window.clearTimeout(this.nextUpdate);
this.nextUpdate = window.setTimeout(contextualCallback(this.toolbar,EditorToolbar.onUpdateButton),easyEditor.buttonDelay);
}
easyEditor.buttonDelay = 200;
//++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
//new functions added by AS 03/2011 for support of more browsers:
easyEditor.prototype.initContent=function(iframe,content){
jQuery(iframe).contents().find('body').attr('edit','text');
jQuery(iframe).attr('id','EasyEditiframe');
//var tempDiv=jQuery('<div></div>')[0];
//wikify(content,tempDiv);//good effort, but no cigar BECAUSE the CONTENT is screwed up after saving
jQuery(iframe).contents().find('body').append(content);
config.macros.SCImagePrefix.handler(null,null,null,null,null,this.tiddler.title);
}
//++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
// TOOLBAR CLASS
function EditorToolbar(target,parent,window){
this.target = target;
this.window=window;
this.elements={};
var tbody=createTiddlyElement(createTiddlyElement(parent,"table"),"tbody");
var row = createTiddlyElement(tbody,"tr");
var buttons = (config.options.txtEasyEditorButtons ? config.options.txtEasyEditorButtons : EditorToolbar.buttonsList).split(",");
for(var i = 0; i < buttons.length; i++){
var temp=buttons[i].split('|');
var n = temp[0]; //command
var l= temp[1] ? temp[1] : null ; //label
var t= temp[2] ? temp[2] : null ; //tooltip
var p= temp[3] ? temp[3] : null ; //parameter
var r= temp[4] ? temp[4] : null ; //prompt text
var c= temp[5] ? temp[5] : null ; //css styling
var button = EditorToolbar.buttons[n] ? EditorToolbar.buttons[n] : null ;
if (button) {
if (button.separator){createTiddlyElement(row,"td",null,"separator").innerHTML+=" ";}
else if (button.textlabel){createTiddlyElement(row,"td",null,"textlabel",button.text);}
else if (button.linebreak){row = createTiddlyElement(tbody,"tr");}
else {
var cell=createTiddlyElement(row,"td",null,n+"Button");
if (button.onCreate) button.onCreate.call(this, cell,n,l,t,p,r,c);
else EditorToolbar.createButton.call(this, cell,n,l,t,p,r,c);
}
} else if (document.queryCommandSupported(n)){
var cell=createTiddlyElement(row,"td",null,n+"Button");
EditorToolbar.createButton.call(this, cell,n,l,t,p,r,c);
}
}
}
EditorToolbar.createButton = function(place,n,l,t,p,r,c){
//console.log('creating toolbar button ->n:'+n+', l:'+l+', t:'+t+', p:'+p+', r:'+r+', c:'+c)
this.elements[n] = createTiddlyButton(place,l?l:EditorToolbar.buttons[n].label,t?t:EditorToolbar.buttons[n].toolTip,contextualCallback(this,EditorToolbar.onCommand(n,p,r)),"button");
cssString='';
if(EditorToolbar.buttons[n] && EditorToolbar.buttons[n].css) cssString=EditorToolbar.buttons[n].css;
cssString= c ? cssString+c : cssString; //user-provided styles override the built-in style
//console.log(cssString);
setStylesheet('.'+n+'Button .button {'+cssString+'}');
}
EditorToolbar.onCommand = function(n,p,r){
var button = EditorToolbar.buttons[n]?EditorToolbar.buttons[n]:null;
return function(){
var parameter = false;
if (p){parameter=p;}
else if (button.prompt||r) {
var parameter = this.target.queryCommandValue(n);
parameter = prompt(r?r:button.prompt,parameter);
}
if (parameter != null) {
this.target.execCommand(n, false, parameter);
EditorToolbar.onUpdateButton.call(this);
}
return false;
}
}
EditorToolbar.getCommandState = function(target,name){
try {return target.queryCommandState(name)}
catch(e){return false}
}
EditorToolbar.onRefreshButton = function (name){
if (EditorToolbar.getCommandState(this.target,name)) addClass(this.elements[name].parentNode,"buttonON");
else removeClass(this.elements[name].parentNode,"buttonON");
this.window.focus();
}
EditorToolbar.onUpdateButton = function(){
for (b in this.elements)
if (EditorToolbar.buttons[b].onRefresh) EditorToolbar.buttons[b].onRefresh.call(this,b);
else EditorToolbar.onRefreshButton.call(this,b);
}
EditorToolbar.buttons = {
linebreak : {linebreak : true},
separator : {separator : true},
bold : {label:"B", toolTip : "Bold", css:'font-weight:bold'},
italic : {label:"I", toolTip : "Italic", css:'font-style:italic;padding-right:0.65em'},
underline : {label:"U", toolTip : "Underline",css:'text-decoration:underline'},
strikethrough : {label:"S", toolTip : "Strikethrough",css:'text-decoration:line-through'},
insertunorderedlist : {label:"\u25CF", toolTip : "Unordered list",css:'margin-left:0.7em'},
insertorderedlist : {label:"1.", toolTip : "Ordered list"},
justifyleft : {label:"[\u2261", toolTip : "Align left", css:'padding-left:0.1em'},
justifyright : {label:"\u2261]", toolTip : "Align right",css:'padding-right:0.1em'},
justifycenter : {label:"\u2261", toolTip : "Align center"},
justifyfull : {label:"[\u2261]", toolTip : "Justify",css:'padding-left:0.1em;padding-right:0.1em'},
removeformat : {label:"\u00F8", toolTip : "Remove format"},
fontsize : {label:"\u00B1", toolTip : "Set font size", prompt: "Enter font size"},
forecolor : {label:"C", toolTip : "Set font color", prompt: "Enter font color (e.g. yellow,red,etc)"},
fontname : {label:"F", toolTip : "Set font name", prompt: "Enter font name",css:'font-family:serif'},
heading : {label:"H", toolTip : "Set heading level", prompt: "Enter heading level (example : h1, h2, ...)"},
indent : {label:"\u2192[", toolTip : "Indent paragraph",css:'padding-left:0.1em;padding-right:0.1em'},
outdent : {label:"[\u2190", toolTip : "Outdent paragraph",css:'padding-left:0.1em;padding-right:0.1em'},
inserthorizontalrule : {label:"\u2014", toolTip : "Insert an horizontal rule"},
insertimage : {label:"\u263C", toolTip : "Insert image", prompt: "Enter image url"}
}
EditorToolbar.buttonsList = "bold,italic,underline,strikethrough,separator,increasefontsize,decreasefontsize,fontsize,forecolor,fontname,separator,removeformat,separator,insertparagraph,insertunorderedlist,insertorderedlist,separator,justifyleft,justifyright,justifycenter,justifyfull,indent,outdent,separator,heading,separator,inserthorizontalrule,insertimage";
if (config.browser.isGecko) {
EditorToolbar.buttons.increasefontsize = {onCreate : EditorToolbar.createButton, label:"A", toolTip : "Increase font size"};
EditorToolbar.buttons.decreasefontsize = {onCreate : EditorToolbar.createButton, label:"A", toolTip : "Decrease font size"};
EditorToolbar.buttons.insertparagraph = {label:"P", toolTip : "Format as paragraph"};
}
// GECKO (FIREFOX, ...) BROWSER SPECIFIC METHODS
geckoEditor.setupFrame = function(iframe,height,callback) {
iframe.setAttribute("style","width: 100%; height:" + height);
iframe.addEventListener("load",callback,true);
}
geckoEditor.plugEvents = function(doc,onchange){
doc.addEventListener("keyup", onchange, true);
doc.addEventListener("keydown", onchange, true);
doc.addEventListener("click", onchange, true);
}
geckoEditor.postProcessor = function(text){return text};
geckoEditor.preProcessor = function(text){return easyEditor.SimplePreProcessoror(text)}
geckoEditor.isDocReady = function() {return true;}
geckoEditor.reloadOnDesignMode=false;
geckoEditor.initContent = function(doc,content){
if (content) doc.execCommand("insertHTML",false,geckoEditor.preProcessor(content));
}
// INTERNET EXPLORER BROWSER SPECIFIC METHODS
IEeditor.setupFrame = function(iframe,height,callback) {
iframe.width="99%"; //IE displays the iframe at the bottom if 100%. CSS layout problem ? I don't know. To be studied...
iframe.height=height.toString();
iframe.attachEvent("onreadystatechange",callback);
}
IEeditor.plugEvents = function(doc,onchange){
doc.attachEvent("onkeyup", onchange);
doc.attachEvent("onkeydown", onchange);
doc.attachEvent("onclick", onchange);
}
IEeditor.isDocReady = function(doc){
if (doc.readyState!="complete") return false;
if (!doc.body) return false;
return (doc && doc.getElementsByTagName && doc.getElementsByTagName("head") && doc.getElementsByTagName("head").length>0);
}
IEeditor.postProcessor = function(text){return text};
IEeditor.preProcessor = function(text){return easyEditor.SimplePreProcessoror(text)}
IEeditor.reloadOnDesignMode=true;
IEeditor.initContent = function(doc,content){
if (content) doc.body.innerHTML=IEeditor.preProcessor(content);
}
function contextualCallback(obj,func){
return function(){return func.call(obj)}
}
Story.prototype.previousGatherSaveEasyEdit = Story.prototype.previousGatherSaveEasyEdit ? Story.prototype.previousGatherSaveEasyEdit : Story.prototype.gatherSaveFields; // to avoid looping if this line is called several times
Story.prototype.gatherSaveFields = function(e,fields){
if(e && e.getAttribute) {
var f = e.getAttribute("easyEdit");
if(f){
var newVal = config.macros.easyEdit.gather(e);
if (newVal) fields[f] = newVal;
}
this.previousGatherSaveEasyEdit(e, fields);
}
}
config.commands.easyEdit={
text: "edit+",
tooltip: "annotate this section",
readOnlyText: "view",
readOnlyTooltip: "View the source of this tiddler",
handler : function(event,src,title) {
clearMessage();
var tiddlerElem = document.getElementById(story.idPrefix + title);
var fields = tiddlerElem.getAttribute("tiddlyFields");
story.displayTiddler(null,title,"EasyEdit+Template",false,null,fields);
return false;
}
}
config.shadowTiddlers.EasyEditToolBarStyleSheet = "/*{{{*/\n";
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar {font-size:0.8em}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".editor iframe {border:1px solid #DDD}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar td{border:1px solid #888; padding:2px 1px 2px 1px; vertical-align:middle}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar td.separator{border:0}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .button{border:0;color:#444}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .button:hover{background-color:transparent}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .button:active{background-color:transparent}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .buttonON{background-color:#EEE}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar {margin:0.25em 0}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet +="/*}}}*/";
store.addNotification("EasyEditToolBarStyleSheet", refreshStyles);
config.shadowTiddlers.EasyEditDocStyleSheet = "/*{{{*/\n \n/*}}}*/";
if (config.annotations) config.annotations.EasyEditDocStyleSheet = "This stylesheet is applied when editing a text with the wysiwyg easyEditor";
//}}}
/***
!Link button add-on
***/
//{{{
EditorToolbar.createLinkButton = function(place,name) {
this.elements[name] = createTiddlyButton(place,EditorToolbar.buttons[name].label,EditorToolbar.buttons[name].toolTip,contextualCallback(this,EditorToolbar.onInputLink()),"button");
}
EditorToolbar.onInputLink = function() {
return function(){
var browser = config.browser.isGecko ? geckoEditor : (config.browser.isIE ? IEeditor : null);
var value = browser ? browser.getLink(this.target) : "";
value = prompt(EditorToolbar.buttons["createlink"].prompt,value);
if (value) browser.doLink(this.target,value);
else if (value=="") this.target.execCommand("unlink", false, value);
EditorToolbar.onUpdateButton.call(this);
return false;
}
}
EditorToolbar.buttonsList += ",separator,createlink";
EditorToolbar.buttons.createlink = {onCreate : EditorToolbar.createLinkButton, label:"L", toolTip : "Set link", prompt: "Enter link url"};
geckoEditor.getLink=function(doc){
var range=doc.defaultView.getSelection().getRangeAt(0);
var container = range.commonAncestorContainer;
var node = (container.nodeType==3) ? container.parentNode : range.startContainer.childNodes[range.startOffset];
if (node && node.tagName=="A") {
var r=doc.createRange();
r.selectNode(node);
doc.defaultView.getSelection().addRange(r);
return (node.getAttribute("tiddler") ? "#"+node.getAttribute("tiddler") : node.href);
}
else return (container.nodeType==3 ? "#"+container.textContent.substr(range.startOffset, range.endOffset-range.startOffset).replace(/ $/,"") : "");
}
geckoEditor.doLink=function(doc,link){ // store tiddler in a temporary attribute to avoid url encoding of tiddler's name
var pin = "href"+Math.random().toString().substr(3);
doc.execCommand("createlink", false, pin);
var isTiddler=(link.charAt(0)=="#");
var node = doc.defaultView.getSelection().getRangeAt(0).commonAncestorContainer;
var links= (node.nodeType!=3) ? node.getElementsByTagName("a") : [node.parentNode];
for (var cpt=0;cpt<links.length;cpt++)
if (links[cpt].href==pin){
links[cpt].href=isTiddler ? "javascript:;" : link;
links[cpt].setAttribute("tiddler",isTiddler ? link.substr(1) : "");
}
}
geckoEditor.beforeLinkPostProcessor = geckoEditor.beforelinkPostProcessor ? geckoEditor.beforelinkPostProcessor : geckoEditor.postProcessor;
geckoEditor.postProcessor = function(text){
return geckoEditor.beforeLinkPostProcessor(text).replace(/<a tiddler="([^"]*)" href="javascript:;">(.*?)(?:<\/a>)/gi,"[[$2|$1]]").replace(/<a tiddler="" href="/gi,'<a href="');
}
geckoEditor.beforeLinkPreProcessor = geckoEditor.beforeLinkPreProcessor ? geckoEditor.beforeLinkPreProcessor : geckoEditor.preProcessor
geckoEditor.preProcessor = function(text){
return geckoEditor.beforeLinkPreProcessor(text).replace(/\[\[([^|\]]*)\|([^\]]*)]]/g,'<a tiddler="$2" href="javascript:;">$1</a>');
}
IEeditor.getLink=function(doc){
var node=doc.selection.createRange().parentElement();
if (node.tagName=="A") return node.href;
else return (doc.selection.type=="Text"? "#"+doc.selection.createRange().text.replace(/ $/,"") :"");
}
IEeditor.doLink=function(doc,link){
doc.execCommand("createlink", false, link);
}
IEeditor.beforeLinkPreProcessor = IEeditor.beforeLinkPreProcessor ? IEeditor.beforeLinkPreProcessor : IEeditor.preProcessor
IEeditor.preProcessor = function(text){
return IEeditor.beforeLinkPreProcessor(text).replace(/\[\[([^|\]]*)\|([^\]]*)]]/g,'<a ref="#$2">$1</a>');
}
IEeditor.beforeLinkPostProcessor = IEeditor.beforelinkPostProcessor ? IEeditor.beforelinkPostProcessor : IEeditor.postProcessor;
IEeditor.postProcessor = function(text){
return IEeditor.beforeLinkPostProcessor(text).replace(/<a href="#([^>]*)">([^<]*)<\/a>/gi,"[[$2|$1]]");
}
IEeditor.beforeLinkInitContent = IEeditor.beforeLinkInitContent ? IEeditor.beforeLinkInitContent : IEeditor.initContent;
IEeditor.initContent = function(doc,content){
IEeditor.beforeLinkInitContent(doc,content);
var links=doc.body.getElementsByTagName("A");
for (var cpt=0; cpt<links.length; cpt++) {
links[cpt].href=links[cpt].ref; //to avoid IE conversion of relative URLs to absolute
links[cpt].removeAttribute("ref");
}
}
config.shadowTiddlers.EasyEditToolBarStyleSheet += "\n/*{{{*/\n.easyEditorToolBar .createlinkButton .button {color:blue;text-decoration:underline;}\n/*}}}*/";
config.shadowTiddlers.EasyEditDocStyleSheet += "\n/*{{{*/\na {color:#0044BB;font-weight:bold}\n/*}}}*/";
//}}}
/***
!Modifications to detection of changes in tiddlers
Currently,story.gatherSaveFields(tiddler,fields) will return {{{<html></html>}}} on a fresh EasyEdit+ tiddler. This is handled as a 'changed' or 'dirty' tiddler. Here, I hijack story.hasChanges(title) to first detect whether the text is 'just' {{{<html></html>}}}. If it is,
***/
//{{{
//}}}
//{{{
//EditorToolbar.buttons.hilitecolor = {label:"C", toolTip : "Highlight", prompt: "Enter background color"};
//EditorToolbar.buttonsList +=",hilitecolor";
//config.shadowTiddlers.EasyEditToolBarStyleSheet += "\n/*{{{*/\n.easyEditorToolBar .hilitecolorButton .button {background-color:red;color:white;}\n/*}}}*/";
config.commands.easyEditNote=jQuery.extend(true, {}, config.commands.easyEdit);
config.commands.easyEditNote.handler=function (event, src, title) {
clearMessage();
var tiddlerElem = document.getElementById(story.idPrefix + title);
var fields = tiddlerElem.getAttribute("tiddlyFields");
story.displayTiddler(null,title,"NOTESEditTemplate",false,null,fields);
return false;
}
//}}}
<!--{{{-->
<span macro="showWhenThisExists"><span macro="hideWhenTagged NOTES">
<span class='title' macro='view title'></span>
</span></span>
<span macro="showWhenTagged NOTES">
<div class='editor' macro='edit title'></div>
</span>
<span macro="hideWhenThisExists">
<div class='editor' macro='edit title'></div>
</span>
<span macro="showWhenTagged NOTES">
<div class='toolbar' macro='toolbar deleteTiddler'></div>
</span>
<div class='toolbar' macro='toolbar [[ToolbarCommands::EditToolbar]]'></div>
<span macro="showWhen config.options.txtUserName==config.options.adminUserName">
<div class='toolbar' macro='toolbar switchEditMode'></div>
</span>
<div macro='annotations'></div>
<div class='editor' macro='easyEdit text'></div>
<div class='editor' macro='edit tags' style="display:none;"></div>
<!--}}}-->
/*{{{*/
body {color:#444; font-size:0.75em;line-height:1.4em;font-family:arial,helvetica;margin : 0.5em; padding : 0;}
html {border:0}
a, a:link, a:visited, a:active {text-decoration:none;color:#BB4400;font-weight:bold}
ul, ol {margin-left:0.5em;padding-left:1.5em;}
/*}}}*/
/***
|''Name:''|EasyEditPlugin|
|''Description:''|Lite and extensible Wysiwyg editor for TiddlyWiki.|
|''Version:''|1.3.3|
|''Date:''|Dec 21,2007|
|''Source:''|http://visualtw.ouvaton.org/VisualTW.html|
|''Author:''|Pascal Collin|
|''License:''|[[BSD open source license|License]]|
|''~CoreVersion:''|2.1.0|
|''Browser:''|Firefox 2.0; InternetExplorer 6.0|
!Demo
*On the plugin [[homepage|http://visualtw.ouvaton.org/VisualTW.html]], see [[WysiwygDemo]] and use the {{{write}}} button.
!Installation
#import the plugin,
#save and reload,
#use the <<toolbar easyEdit>> button in the tiddler's toolbar (in default ViewTemplate) or add {{{easyEdit}}} command in your own toolbar.
! Useful Addons
*[[HTMLFormattingPlugin|http://www.tiddlytools.com/#HTMLFormattingPlugin]] to embed wiki syntax in html tiddlers.<<br>>//__Tips__ : When this plugin is installed, you can use anchor syntax to link tiddlers in wysiwyg mode (example : #example). Anchors are converted back and from wiki syntax when editing.//
*[[TaggedTemplateTweak|http://www.TiddlyTools.com/#TaggedTemplateTweak]] to use alternative ViewTemplate/EditTemplate for tiddler's tagged with specific tag values.
!Configuration
|Buttons in the toolbar (empty = all).<<br>>//Example : bold,underline,separator,forecolor//<<br>>The buttons will appear in this order.| <<option txtEasyEditorButtons>>|
|EasyEditor default height | <<option txtEasyEditorHeight>>|
|Stylesheet applied to the edited richtext |[[EasyEditDocStyleSheet]]|
|Template called by the {{{write}}} button |[[EasyEditTemplate]]|
!How to extend EasyEditor
*To add your own buttons, add some code like the following in a systemConfig tagged tiddler (//use the prompt attribute only if there is a parameter//) :
**{{{EditorToolbar.buttons.heading = {label:"H", toolTip : "Set heading level", prompt: "Enter heading level"};}}}
**{{{EditorToolbar.buttonsList +=",heading";}}}
*To get the list of all possible commands, see the documentation of the [[Gecko built-in rich text editor|http://developer.mozilla.org/en/docs/Midas]] or the [[IE command identifiers|http://msdn2.microsoft.com/en-us/library/ms533049.aspx]].
*To go further in customization, see [[Link button|EasyEditPlugin-LinkButton]] as an example.
!Code
***/
//{{{
var geckoEditor={};
var IEeditor={};
config.options.txtEasyEditorHeight = config.options.txtEasyEditorHeight ? config.options.txtEasyEditorHeight : "500px";
config.options.txtEasyEditorButtons = config.options.txtEasyEditorButtons ? config.options.txtEasyEditorButtons : "";
// TW2.1.x compatibility
config.browser.isGecko = config.browser.isGecko ? config.browser.isGecko : (config.userAgent.indexOf("gecko") != -1);
config.macros.annotations = config.macros.annotations ? config.macros.annotations : {handler : function() {}}
// EASYEDITOR MACRO
config.macros.easyEdit = {
handler : function(place,macroName,params,wikifier,paramString,tiddler) {
var field = params[0];
var height = params[1] ? params[1] : config.options.txtEasyEditorHeight;
editor = field ? new easyEditor(tiddler,field,place,height) : null;
},
gather: function(element){
var iframes = element.getElementsByTagName("iframe");
if (iframes.length!=1) return null
var text = "<html>"+iframes[0].contentWindow.document.body.innerHTML+"</html>";
text = config.browser.isGecko ? geckoEditor.postProcessor(text) : (config.browser.isIE ? IEeditor.postProcessor(text) : text);
return text;
}
}
// EASYEDITOR CLASS
function easyEditor(tiddler,field,place,height) {
this.tiddler = tiddler;
this.field = field;
this.browser = config.browser.isGecko ? geckoEditor : (config.browser.isIE ? IEeditor : null);
this.wrapper = createTiddlyElement(place,"div",null,"easyEditor");
this.wrapper.setAttribute("easyEdit",this.field);
this.iframe = createTiddlyElement(null,"iframe");
this.browser.setupFrame(this.iframe,height,contextualCallback(this,this.onload));
this.wrapper.appendChild(this.iframe);
}
easyEditor.prototype.onload = function(){
this.editor = this.iframe.contentWindow;
this.doc = this.editor.document;
if (!this.browser.isDocReady(this.doc)) return null;
if (!this.tiddler.isReadOnly() && this.doc.designMode.toLowerCase()!="on") {
this.doc.designMode = "on";
if (this.browser.reloadOnDesignMode) return false; // IE fire readystatechange after designMode change
}
var internalCSS = store.getTiddlerText("EasyEditDocStyleSheet");
setStylesheet(internalCSS,"EasyEditDocStyleSheet",this.doc);
this.browser.initContent(this.doc,store.getValue(this.tiddler,this.field));
var barElement=createTiddlyElement(null,"div",null,"easyEditorToolBar");
this.wrapper.insertBefore(barElement,this.wrapper.firstChild);
this.toolbar = new EditorToolbar(this.doc,barElement,this.editor);
this.browser.plugEvents(this.doc,contextualCallback(this,this.scheduleButtonsRefresh));
this.editor.focus();
}
easyEditor.SimplePreProcessoror = function(text) {
var re = /^<html>(.*)<\/html>$/m;
var htmlValue = re.exec(text);
var value = (htmlValue && (htmlValue.length>0)) ? htmlValue[1] : text;
return value;
}
easyEditor.prototype.scheduleButtonsRefresh=function() { //doesn't refresh buttons state when rough typing
if (this.nextUpdate) window.clearTimeout(this.nextUpdate);
this.nextUpdate = window.setTimeout(contextualCallback(this.toolbar,EditorToolbar.onUpdateButton),easyEditor.buttonDelay);
}
easyEditor.buttonDelay = 200;
// TOOLBAR CLASS
function EditorToolbar(target,parent,window){
this.target = target;
this.window=window;
this.elements={};
var row = createTiddlyElement(createTiddlyElement(createTiddlyElement(parent,"table"),"tbody"),"tr");
var buttons = (config.options.txtEasyEditorButtons ? config.options.txtEasyEditorButtons : EditorToolbar.buttonsList).split(",");
for(var cpt = 0; cpt < buttons.length; cpt++){
var b = buttons[cpt];
var button = EditorToolbar.buttons[b];
if (button) {
if (button.separator)
createTiddlyElement(row,"td",null,"separator").innerHTML+=" ";
else {
var cell=createTiddlyElement(row,"td",null,b+"Button");
if (button.onCreate) button.onCreate.call(this, cell, b);
else EditorToolbar.createButton.call(this, cell, b);
}
}
}
}
EditorToolbar.createButton = function(place,name){
this.elements[name] = createTiddlyButton(place,EditorToolbar.buttons[name].label,EditorToolbar.buttons[name].toolTip,contextualCallback(this,EditorToolbar.onCommand(name)),"button");
}
EditorToolbar.onCommand = function(name){
var button = EditorToolbar.buttons[name];
return function(){
var parameter = false;
if (button.prompt) {
var parameter = this.target.queryCommandValue(name);
parameter = prompt(button.prompt,parameter);
}
if (parameter != null) {
this.target.execCommand(name, false, parameter);
EditorToolbar.onUpdateButton.call(this);
}
return false;
}
}
EditorToolbar.getCommandState = function(target,name){
try {return target.queryCommandState(name)}
catch(e){return false}
}
EditorToolbar.onRefreshButton = function (name){
if (EditorToolbar.getCommandState(this.target,name)) addClass(this.elements[name].parentNode,"buttonON");
else removeClass(this.elements[name].parentNode,"buttonON");
this.window.focus();
}
EditorToolbar.onUpdateButton = function(){
for (b in this.elements)
if (EditorToolbar.buttons[b].onRefresh) EditorToolbar.buttons[b].onRefresh.call(this,b);
else EditorToolbar.onRefreshButton.call(this,b);
}
EditorToolbar.buttons = {
separator : {separator : true},
bold : {label:"B", toolTip : "Bold"},
italic : {label:"I", toolTip : "Italic"},
underline : {label:"U", toolTip : "Underline"},
strikethrough : {label:"S", toolTip : "Strikethrough"},
insertunorderedlist : {label:"\u25CF", toolTip : "Unordered list"},
insertorderedlist : {label:"1.", toolTip : "Ordered list"},
justifyleft : {label:"[\u2261", toolTip : "Align left"},
justifyright : {label:"\u2261]", toolTip : "Align right"},
justifycenter : {label:"\u2261", toolTip : "Align center"},
justifyfull : {label:"[\u2261]", toolTip : "Justify"},
removeformat : {label:"\u00F8", toolTip : "Remove format"},
fontsize : {label:"\u00B1", toolTip : "Set font size", prompt: "Enter font size"},
forecolor : {label:"C", toolTip : "Set font color", prompt: "Enter font color"},
fontname : {label:"F", toolTip : "Set font name", prompt: "Enter font name"},
heading : {label:"H", toolTip : "Set heading level", prompt: "Enter heading level (example : h1, h2, ...)"},
indent : {label:"\u2192[", toolTip : "Indent paragraph"},
outdent : {label:"[\u2190", toolTip : "Outdent paragraph"},
inserthorizontalrule : {label:"\u2014", toolTip : "Insert an horizontal rule"},
insertimage : {label:"\u263C", toolTip : "Insert image", prompt: "Enter image url"}
}
EditorToolbar.buttonsList = "bold,italic,underline,strikethrough,separator,increasefontsize,decreasefontsize,fontsize,forecolor,fontname,separator,removeformat,separator,insertparagraph,insertunorderedlist,insertorderedlist,separator,justifyleft,justifyright,justifycenter,justifyfull,indent,outdent,separator,heading,separator,inserthorizontalrule,insertimage";
if (config.browser.isGecko) {
EditorToolbar.buttons.increasefontsize = {onCreate : EditorToolbar.createButton, label:"A", toolTip : "Increase font size"};
EditorToolbar.buttons.decreasefontsize = {onCreate : EditorToolbar.createButton, label:"A", toolTip : "Decrease font size"};
EditorToolbar.buttons.insertparagraph = {label:"P", toolTip : "Format as paragraph"};
}
// GECKO (FIREFOX, ...) BROWSER SPECIFIC METHODS
geckoEditor.setupFrame = function(iframe,height,callback) {
iframe.setAttribute("style","width: 100%; height:" + height);
iframe.addEventListener("load",callback,true);
}
geckoEditor.plugEvents = function(doc,onchange){
doc.addEventListener("keyup", onchange, true);
doc.addEventListener("keydown", onchange, true);
doc.addEventListener("click", onchange, true);
}
geckoEditor.postProcessor = function(text){return text};
geckoEditor.preProcessor = function(text){return easyEditor.SimplePreProcessoror(text)}
geckoEditor.isDocReady = function() {return true;}
geckoEditor.reloadOnDesignMode=false;
geckoEditor.initContent = function(doc,content){
if (content) doc.execCommand("insertHTML",false,geckoEditor.preProcessor(content));
}
// INTERNET EXPLORER BROWSER SPECIFIC METHODS
IEeditor.setupFrame = function(iframe,height,callback) {
iframe.width="99%"; //IE displays the iframe at the bottom if 100%. CSS layout problem ? I don't know. To be studied...
iframe.height=height.toString();
iframe.attachEvent("onreadystatechange",callback);
}
IEeditor.plugEvents = function(doc,onchange){
doc.attachEvent("onkeyup", onchange);
doc.attachEvent("onkeydown", onchange);
doc.attachEvent("onclick", onchange);
}
IEeditor.isDocReady = function(doc){
if (doc.readyState!="complete") return false;
if (!doc.body) return false;
return (doc && doc.getElementsByTagName && doc.getElementsByTagName("head") && doc.getElementsByTagName("head").length>0);
}
IEeditor.postProcessor = function(text){return text};
IEeditor.preProcessor = function(text){return easyEditor.SimplePreProcessoror(text)}
IEeditor.reloadOnDesignMode=true;
IEeditor.initContent = function(doc,content){
if (content) doc.body.innerHTML=IEeditor.preProcessor(content);
}
function contextualCallback(obj,func){
return function(){return func.call(obj)}
}
Story.prototype.previousGatherSaveEasyEdit = Story.prototype.previousGatherSaveEasyEdit ? Story.prototype.previousGatherSaveEasyEdit : Story.prototype.gatherSaveFields; // to avoid looping if this line is called several times
Story.prototype.gatherSaveFields = function(e,fields){
if(e && e.getAttribute) {
var f = e.getAttribute("easyEdit");
if(f){
var newVal = config.macros.easyEdit.gather(e);
if (newVal) fields[f] = newVal;
}
this.previousGatherSaveEasyEdit(e, fields);
}
}
config.commands.easyEdit={
text: "write",
tooltip: "Edit this tiddler in wysiwyg mode",
readOnlyText: "view",
readOnlyTooltip: "View the source of this tiddler",
handler : function(event,src,title) {
clearMessage();
var tiddlerElem = document.getElementById(story.idPrefix + title);
var fields = tiddlerElem.getAttribute("tiddlyFields");
story.displayTiddler(null,title,"EasyEditTemplate",false,null,fields);
return false;
}
}
config.shadowTiddlers.ViewTemplate = config.shadowTiddlers.ViewTemplate.replace(/\+editTiddler/,"+editTiddler easyEdit");
config.shadowTiddlers.EasyEditTemplate = config.shadowTiddlers.EditTemplate.replace(/macro='edit text'/,"macro='easyEdit text'");
config.shadowTiddlers.EasyEditToolBarStyleSheet = "/*{{{*/\n";
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar {font-size:0.8em}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".editor iframe {border:1px solid #DDD}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar td{border:1px solid #888; padding:2px 1px 2px 1px; vertical-align:middle}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar td.separator{border:0}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .button{border:0;color:#444}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .buttonON{background-color:#EEE}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar {margin:0.25em 0}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .boldButton {font-weight:bold}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .italicButton .button {font-style:italic;padding-right:0.65em}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .underlineButton .button {text-decoration:underline}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .strikeButton .button {text-decoration:line-through}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .unorderedListButton {margin-left:0.7em}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .justifyleftButton .button {padding-left:0.1em}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .justifyrightButton .button {padding-right:0.1em}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .justifyfullButton .button, .easyEditorToolBar .indentButton .button, .easyEditorToolBar .outdentButton .button {padding-left:0.1em;padding-right:0.1em}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .increasefontsizeButton .button {padding-left:0.15em;padding-right:0.15em; font-size:1.3em; line-height:0.75em}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .decreasefontsizeButton .button {padding-left:0.4em;padding-right:0.4em; font-size:0.8em;}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .forecolorButton .button {color:red;}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet += ".easyEditorToolBar .fontnameButton .button {font-family:serif}\n" ;
config.shadowTiddlers.EasyEditToolBarStyleSheet +="/*}}}*/";
store.addNotification("EasyEditToolBarStyleSheet", refreshStyles);
config.shadowTiddlers.EasyEditDocStyleSheet = "/*{{{*/\n \n/*}}}*/";
if (config.annotations) config.annotations.EasyEditDocStyleSheet = "This stylesheet is applied when editing a text with the wysiwyg easyEditor";
//}}}
/***
!Link button add-on
***/
//{{{
EditorToolbar.createLinkButton = function(place,name) {
this.elements[name] = createTiddlyButton(place,EditorToolbar.buttons[name].label,EditorToolbar.buttons[name].toolTip,contextualCallback(this,EditorToolbar.onInputLink()),"button");
}
EditorToolbar.onInputLink = function() {
return function(){
var browser = config.browser.isGecko ? geckoEditor : (config.browser.isIE ? IEeditor : null);
var value = browser ? browser.getLink(this.target) : "";
value = prompt(EditorToolbar.buttons["createlink"].prompt,value);
if (value) browser.doLink(this.target,value);
else if (value=="") this.target.execCommand("unlink", false, value);
EditorToolbar.onUpdateButton.call(this);
return false;
}
}
EditorToolbar.buttonsList += ",separator,createlink";
EditorToolbar.buttons.createlink = {onCreate : EditorToolbar.createLinkButton, label:"L", toolTip : "Set link", prompt: "Enter link url"};
geckoEditor.getLink=function(doc){
var range=doc.defaultView.getSelection().getRangeAt(0);
var container = range.commonAncestorContainer;
var node = (container.nodeType==3) ? container.parentNode : range.startContainer.childNodes[range.startOffset];
if (node && node.tagName=="A") {
var r=doc.createRange();
r.selectNode(node);
doc.defaultView.getSelection().addRange(r);
return (node.getAttribute("tiddler") ? "#"+node.getAttribute("tiddler") : node.href);
}
else return (container.nodeType==3 ? "#"+container.textContent.substr(range.startOffset, range.endOffset-range.startOffset).replace(/ $/,"") : "");
}
geckoEditor.doLink=function(doc,link){ // store tiddler in a temporary attribute to avoid url encoding of tiddler's name
var pin = "href"+Math.random().toString().substr(3);
doc.execCommand("createlink", false, pin);
var isTiddler=(link.charAt(0)=="#");
var node = doc.defaultView.getSelection().getRangeAt(0).commonAncestorContainer;
var links= (node.nodeType!=3) ? node.getElementsByTagName("a") : [node.parentNode];
for (var cpt=0;cpt<links.length;cpt++)
if (links[cpt].href==pin){
links[cpt].href=isTiddler ? "javascript:;" : link;
links[cpt].setAttribute("tiddler",isTiddler ? link.substr(1) : "");
}
}
geckoEditor.beforeLinkPostProcessor = geckoEditor.beforelinkPostProcessor ? geckoEditor.beforelinkPostProcessor : geckoEditor.postProcessor;
geckoEditor.postProcessor = function(text){
return geckoEditor.beforeLinkPostProcessor(text).replace(/<a tiddler="([^"]*)" href="javascript:;">(.*?)(?:<\/a>)/gi,"[[$2|$1]]").replace(/<a tiddler="" href="/gi,'<a href="');
}
geckoEditor.beforeLinkPreProcessor = geckoEditor.beforeLinkPreProcessor ? geckoEditor.beforeLinkPreProcessor : geckoEditor.preProcessor
geckoEditor.preProcessor = function(text){
return geckoEditor.beforeLinkPreProcessor(text).replace(/\[\[([^|\]]*)\|([^\]]*)]]/g,'<a tiddler="$2" href="javascript:;">$1</a>');
}
IEeditor.getLink=function(doc){
var node=doc.selection.createRange().parentElement();
if (node.tagName=="A") return node.href;
else return (doc.selection.type=="Text"? "#"+doc.selection.createRange().text.replace(/ $/,"") :"");
}
IEeditor.doLink=function(doc,link){
doc.execCommand("createlink", false, link);
}
IEeditor.beforeLinkPreProcessor = IEeditor.beforeLinkPreProcessor ? IEeditor.beforeLinkPreProcessor : IEeditor.preProcessor
IEeditor.preProcessor = function(text){
return IEeditor.beforeLinkPreProcessor(text).replace(/\[\[([^|\]]*)\|([^\]]*)]]/g,'<a ref="#$2">$1</a>');
}
IEeditor.beforeLinkPostProcessor = IEeditor.beforelinkPostProcessor ? IEeditor.beforelinkPostProcessor : IEeditor.postProcessor;
IEeditor.postProcessor = function(text){
return IEeditor.beforeLinkPostProcessor(text).replace(/<a href="#([^>]*)">([^<]*)<\/a>/gi,"[[$2|$1]]");
}
IEeditor.beforeLinkInitContent = IEeditor.beforeLinkInitContent ? IEeditor.beforeLinkInitContent : IEeditor.initContent;
IEeditor.initContent = function(doc,content){
IEeditor.beforeLinkInitContent(doc,content);
var links=doc.body.getElementsByTagName("A");
for (var cpt=0; cpt<links.length; cpt++) {
links[cpt].href=links[cpt].ref; //to avoid IE conversion of relative URLs to absolute
links[cpt].removeAttribute("ref");
}
}
config.shadowTiddlers.EasyEditToolBarStyleSheet += "\n/*{{{*/\n.easyEditorToolBar .createlinkButton .button {color:blue;text-decoration:underline;}\n/*}}}*/";
config.shadowTiddlers.EasyEditDocStyleSheet += "\n/*{{{*/\na {color:#0044BB;font-weight:bold}\n/*}}}*/";
//}}}
/***
|Name|EditSectionPlugin|
|Source|http://www.TiddlyTools.com/#EditSectionPlugin|
|Documentation|http://www.TiddlyTools.com/#EditSectionPlugin|
|Version|1.5.1|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|invoke popup 'section editor' for specified section of a tiddler|
!!!!!Usage
<<<
{{{
<<editSection TiddlerName##sectionname label tooltip>>
}}}
where:
* ''~TiddlerName##sectionname'' specifies the tiddler and section you want to edit.
** If you omit the "##sectionname" portion (i.e., only enter "~TiddlerName"), the entire content of the indicated tiddler is edited.
** If you omit the "~TiddlerName" portion (i.e., only enter "##sectionname"), the current containing tiddler (if any) is assumed.
** Changing the section name in the popup editor //renames// that section within the tiddler.
** Changing the tiddler title in the popup editor //copies// that section to another tiddler.
** If the indicated tiddler and/or section does not yet exist, it will be created when you press 'save'.
* ''label'' and ''tooltip'' (both //optional//) specify the link label and mouseover help text for the 'edit section' command link.
Note: when a document is viewed in 'readOnly' mode, the macro is bypassed and a command link is not rendered.
<<<
!!!!!Sample
<<<
This is a sample section for you to try
<<<
!!!!!Example
<<<
{{{
<<editSection ##Sample>>
}}}
<<editSection ##Sample>>
<<<
!!!!!Configuration
<<<
To customize and/or translate the HTML form layout used to render the section editor, edit the [[EditSectionTemplate]] shadow tiddler.
<<<
!!!!!Revisions
<<<
2011.01.09 1.5.1 in handler(), don't render command link if document is readOnly
2010.12.24 1.5.0 replace use of core Popups with custom panel handling (bypass core interactions and errors)
2010.11.07 1.4.0 in popup(), render HTML form from EditSectionTemplate, and then applyHtmlMacros() to render wiki-syntax macro-generated form elements (e.g., {{{<<option>>, <<select>>}}}, etc.). Also, refactored form init/save handling to add customization 'hooks'
2010.10.25 1.3.0 added support for editing complete tiddlers using "~TiddlerName" syntax (omit "##sectionname")
2010.07.15 1.2.0 added confirmation when section rename will overwrite other section
2010.07.13 1.1.1 added 'dirty flag' confirmation to popup handling to avoid discarding unsaved changes
2010.07.11 1.1.0 fixed handling for creating new sections in existing tiddlers. Copied StickyPopupPlugin to eliminate dependency. Added Popup.showHere()
2010.05.24 1.0.2 in save(), escape regexp chars in section titles (e.g. "!SectionNameWith?InIt")
2009.09.07 1.0.1 documentation/code cleanup
2009.09.01 1.0.0 initial release
<<<
!!!!!Code
***/
//{{{
version.extensions.EditSectionPlugin= {major: 1, minor: 5, revision: 1, date: new Date(2011,1,9)};
config.macros.editSection = {
label: 'edit section...',
tip: 'edit %0',
sectionfmt: '{{hidden{\n!%0\n%1\n!end\n}}}',
sectionerr: 'Invalid tiddler/section name: %0',
newtiddlertxt: '',
discardmsg: 'Discard unsaved changes for %0%1%2?',
overwritemsg: '%0##%2 already exists. Choose OK to overwrite it',
template: 'EditSectionTemplate',
init: function() {
// SHADOW PAYLOAD FOR EditSectionTemplate FORM DEFINITION
config.shadowTiddlers[this.template]
=store.getTiddlerText('EditSectionPlugin##HTML','');
// CLOSE PANELS IF CLICK on other than POPUP OR EDITOR PANEL
addEvent(document,'click',function(ev) {
var p=resolveTarget(ev||window.event);
while (p) {
if (hasClass(p,'editSectionPanel')) break;
if (hasClass(p,'popup')) break;
p=p.parentNode;
}
if (!p) config.macros.editSection.removeAllPanels();
return true;
});
// HIJACK QuickEditPlugin's getField() to support use with editSectionPanel
if (config.quickEdit) {
config.quickEdit.getTiddlerField=config.quickEdit.getField;
config.quickEdit.getField=function(where) {
var e=where; while(e) { if (hasClass(e,'editSectionPanel')) break; e=e.parentNode; }
return e?e.getElementsByTagName('textarea')[0]:this.getTiddlerField(where);
}
}
},
handler: function(place,macroName,params,wikifier,paramString,tiddler) {
if (readOnly) return;
var here=story.findContainingTiddler(place);
var tid=params[0];
var label=params[1]||this.label.format([tid]);
var tip=params[2]||this.tip.format([tid]);
var btn=createTiddlyButton(place,label,tip,this.click);
btn.setAttribute('tid',tid);
},
processed: function(ev) {
ev.cancelBubble=true;
if(ev.stopPropagation)ev.stopPropagation();
return false;
},
click: function(ev,template,initForm,saveForm) {
var parts=this.getAttribute('tid').split('##');
var title=parts[0]; var section=parts[1];
var here=story.findContainingTiddler(this);
if (!title&&here) title=here.getAttribute('tiddler');
if (!title) return false;
return config.macros.editSection.createPanel(this,ev,title,section,template,initForm,saveForm);
},
createPanel: function(here,ev,title,section,template,initForm,saveForm) {
if (!this.removeAllPanels()) return this.processed(ev);
var p=createTiddlyElement(document.body,"ol","popup","popup smallform editSectionPanel");
p.root=here;
p.setAttribute('dirty',null);
p.setAttribute('message',this.discardmsg.format([title,section?'##':'',section]));
p.innerHTML=store.getRecursiveTiddlerText(template||this.template,'',10);
applyHtmlMacros(p,store.getTiddler(title));
var f=p.getElementsByTagName('form')[0];
this.initPanel(p,here,f,title,section,initForm,saveForm);
this.showPanel(p,here,ev);
return this.processed(ev);
},
initPanel: function(p,here,f,title,section,initForm,saveForm) {
f.panel=p;
f.title.value=title;
f.section.value=section;
f.newsection.value=title+(section?'##'+section:'');
f.content.value=store.getTiddlerText(f.newsection.value,'');
if (version.extensions.TextAreaPlugin) new window.TextAreaResizer(f.content);
f.initForm=initForm;
f.saveForm=saveForm;
if (f.initForm) f.initForm(here,f,title,section);
},
showPanel: function(p,here,ev) {
var x=ev.pageX; var y=ev.pageY;
if (config.browser.isIE) { x=ev.clientX+findScrollX(); y=ev.clientY+findScrollY(); }
var winw=findWindowWidth();
var scrollw=winw-document.body.offsetWidth;
if(p.offsetWidth>winw*0.75) p.style.width=winw*0.75 + "px";
if(x+p.offsetWidth>winw-scrollw-1) x=winw-p.offsetWidth-scrollw-1;
var s=p.style; s.left=x+'px'; s.top=y+'px'; s.display='block';
if(config.options.chkAnimate && anim) anim.startAnimating(new Scroller(p));
else window.scrollTo(0,ensureVisible(p));
},
removePanel: function(p) {
if (!p || p.getAttribute('dirty')!='true' || confirm(p.getAttribute('message')))
{ if (p) removeNode(p); return true; }
return false;
},
removeAllPanels: function() {
var ok=true;
jQuery('.editSectionPanel').each(function(index){
var f=this.getElementsByTagName('form')[0];
f.content.blur(); // force onchange (sets 'dirty' flag as needed)
ok=config.macros.editSection.removePanel(this);
return true;
});
return ok; // FALSE if panels remain
},
changed: function(here,ev) {
here.form.panel.setAttribute('dirty','true');
return this.processed(ev);
},
cancel: function(here,ev) {
this.removePanel(here.form.panel);
return this.processed(ev);
},
save: function(here,ev) {
var f=here.form;
// GET TARGET TITLE/SECTION
var tid=f.newsection.value;
var parts=tid.split('##');
var title=parts[0];
var section=parts[1];
var where=here.form.panel.root;
if (!title) title=story.findContainingTiddler(where).getAttribute('tiddler');
if (!title) {
displayMessage(this.sectionerr.format([f.newsection.value]));
f.newsection.focus(); f.newsection.select(); return false;
}
// GET (or CREATE) TIDDLER
var t=store.getTiddler(title);
var who =t&&config.options.chkForceMinorUpdate?t.modifier:config.options.txtUserName;
var when=t&&config.options.chkForceMinorUpdate?t.modified:new Date();
if (!t) {
t=new Tiddler(); t.text=store.getTiddlerText(title,'');
if (section&&!t.text.length) t.text=this.newtiddlertxt.format([title,section]);
}
// GET NEW CONTENT FROM FORM CONTROLS (DEFAULT = TEXT CONTENT ONLY)
var txt=f.saveForm?f.saveForm(where,f):f.content.value;
// CHECK FOR TIDDLER OVERWRITE
if (!section && title!=f.title.value && store.tiddlerExists(title)) {
if (!confirm(config.messages.overwriteWarning.format([title])))
{ f.newsection.focus(); f.newsection.select(); return this.processed(ev); }
}
// ADD/REVISE/RENAME SECTION CONTENT (if any)
if (section) {
// GET SECTION VALUES
var oldsection=f.section.value;
var oldval=store.getTiddlerText(title+'##'+oldsection); // previous section value
var newval=txt; // revised section value
var existingval=store.getTiddlerText(title+'##'+section); // existing section value
// REVISE TIDDLER TEXT
var txt=t.text; // default tiddler text = unchanged
var pattern=new RegExp('(.*!{1,6})'+oldsection.escapeRegExp()+'\\n'
+(oldval||'').escapeRegExp()+'((?:\\n!{1,6}|$).*)');
var altpattern=this.sectionfmt.format([oldsection,oldval||'']);
if (section!=oldsection && existingval) { // rename overwrites another section...
if (!confirm(this.overwritemsg.format([title,section])))
return this.processed(ev);
txt=txt.replace(altpattern,''); // REMOVE old section (auto-generated)
txt=txt.replace(pattern,'$2'); // REMOVE old section (generic format)
// TARGET new section name and value
pattern=new RegExp('(.*!{1,6})'+section.escapeRegExp()+'\\n'
+existingval.escapeRegExp()+'((?:\\n!{1,6}|$).*)');
oldval=existingval;
}
if (typeof oldval=="string") // section exists... update/rename it
txt=txt.replace(pattern,'$1'+section+'\n'+newval+'$2');
else // otherwise, append a new section to end of tiddler
txt=txt+this.sectionfmt.format([section,newval]);
}
// SAVE TIDDLER
store.saveTiddler(title,title,txt,who,when,t.tags,t.fields);
story.refreshTiddler(title,null,true);
f.panel.setAttribute('dirty',null);
this.removePanel(f.panel);
return this.processed(ev);
}
}
//}}}
/***
//{{{
!HTML
<!--{{{-->
<!--
|Name|EditSectionTemplate|
|Source||
|Version||
|Author||
|License|http://www.TiddlyTools.com/#LegalStatements|
|Type|template|
|Requires|EditSectionPlugin|
|Description|popup editor form template used by EditSectionPlugin|
-->
<form action='javascript:;' style="white-space:nowrap">
<input type="hidden" name="title" value="">
<input type="hidden" name="section" value="">
<input type="text" name="newsection" value="" autocomplete="off" style="width:73%"
onchange="return config.macros.editSection.changed(this,event);">
<input type=button value="save" style="width:12%"
onclick="return config.macros.editSection.save(this,event)">
<input type=button value="cancel" style="width:12%"
onclick="return config.macros.editSection.cancel(this,event)">
<div macro="tiddler QuickEditToolbar"></div>
<textarea name="content" rows="15" cols="80" autocomplete="off"
onchange="return config.macros.editSection.changed(this,event)"></textarea>
</form>
<!--}}}-->
!end
//}}}
***/
<!--{{{-->
<span class='editor' macro='edit title'></span>
<span macro="showWhen config.options.txtUserName==config.options.adminUserName"><span class='toolbar' macro='toolbar deleteTiddler'></span></span><span class='toolbar' macro='toolbar [[ToolbarCommands::EditToolbar]]'></span>
<div macro='annotations'></div>
<div class='editor' macro='edit text'></div>
<div class='editor' macro='edit tags'></div><div class='editorFooter'><span macro='message views.editor.tagPrompt'></span><span macro='tagChooser excludeLists'></span></div>
<!--}}}-->
/***
|Name|ExportTiddlersPlugin|
|Source|http://www.TiddlyTools.com/#ExportTiddlersPlugin|
|Documentation|http://www.TiddlyTools.com/#ExportTiddlersPluginInfo|
|Version|2.9.6|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|interactively select/export tiddlers to a separate file|
!!!!!Documentation
>see [[ExportTiddlersPluginInfo]]
!!!!!Inline control panel (live):
><<exportTiddlers inline>>
!!!!!Revisions
<<<
2011.02.14 2.9.6 fix OSX error: use picker.file.path
2010.02.25 2.9.5 added merge checkbox option and improved 'merge' status message
|please see [[ExportTiddlersPluginInfo]] for additional revision details|
2005.10.09 0.0.0 development started
<<<
!!!!!Code
***/
//{{{
// version
version.extensions.ExportTiddlersPlugin= {major: 2, minor: 9, revision: 6, date: new Date(2011,2,14)};
// default shadow definition
config.shadowTiddlers.ExportTiddlers='<<exportTiddlers inline>>';
// add 'export' backstage task (following built-in import task)
if (config.tasks) { // TW2.2 or above
config.tasks.exportTask = {
text:'export',
tooltip:'Export selected tiddlers to another file',
content:'<<exportTiddlers inline>>'
}
config.backstageTasks.splice(config.backstageTasks.indexOf('importTask')+1,0,'exportTask');
}
config.macros.exportTiddlers = {
$: function(id) { return document.getElementById(id); }, // abbreviation
label: 'export tiddlers',
prompt: 'Copy selected tiddlers to an export document',
okmsg: '%0 tiddler%1 written to %2',
failmsg: 'An error occurred while creating %1',
overwriteprompt: '%0\ncontains %1 tiddler%2 that will be discarded or replaced',
mergestatus: '%0 tiddler%1 added, %2 tiddler%3 updated, %4 tiddler%5 unchanged',
statusmsg: '%0 tiddler%1 - %2 selected for export',
newdefault: 'export.html',
datetimefmt: '0MM/0DD/YYYY 0hh:0mm:0ss', // for 'filter date/time' edit fields
type_TW: "tw", type_PS: "ps", type_TX: "tx", type_CS: "cs", type_NF: "nf", // file type tokens
type_map: { // maps type param to token values
tiddlywiki:"tw", tw:"tw", wiki: "tw",
purestore: "ps", ps:"ps", store:"ps",
plaintext: "tx", tx:"tx", text: "tx",
comma: "cs", cs:"cs", csv: "cs",
newsfeed: "nf", nf:"nf", xml: "nf", rss:"nf"
},
handler: function(place,macroName,params) {
if (params[0]!='inline')
{ createTiddlyButton(place,this.label,this.prompt,this.togglePanel); return; }
var panel=this.createPanel(place);
panel.style.position='static';
panel.style.display='block';
},
createPanel: function(place) {
var panel=this.$('exportPanel');
if (panel) { panel.parentNode.removeChild(panel); }
setStylesheet(store.getTiddlerText('ExportTiddlersPlugin##css',''),'exportTiddlers');
panel=createTiddlyElement(place,'span','exportPanel',null,null)
panel.innerHTML=store.getTiddlerText('ExportTiddlersPlugin##html','');
this.initFilter();
this.refreshList(0);
var fn=this.$('exportFilename');
if (window.location.protocol=='file:' && !fn.value.length) {
// get new target path/filename
var newPath=getLocalPath(window.location.href);
var slashpos=newPath.lastIndexOf('/'); if (slashpos==-1) slashpos=newPath.lastIndexOf('\\');
if (slashpos!=-1) newPath=newPath.substr(0,slashpos+1); // trim filename
fn.value=newPath+this.newdefault;
}
return panel;
},
togglePanel: function(e) { var e=e||window.event;
var cme=config.macros.exportTiddlers; // abbrev
var parent=resolveTarget(e).parentNode;
var panel=cme.$('exportPanel');
if (panel==undefined || panel.parentNode!=parent)
panel=cme.createPanel(parent);
var isOpen=panel.style.display=='block';
if(config.options.chkAnimate)
anim.startAnimating(new Slider(panel,!isOpen,e.shiftKey || e.altKey,'none'));
else
panel.style.display=isOpen?'none':'block' ;
if (panel.style.display!='none') {
cme.refreshList(0);
cme.$('exportFilename').focus();
cme.$('exportFilename').select();
}
e.cancelBubble = true; if (e.stopPropagation) e.stopPropagation(); return(false);
},
process: function(which) { // process panel control interactions
var theList=this.$('exportList'); if (!theList) return false;
var count = 0;
var total = store.getTiddlers('title').length;
switch (which.id) {
case 'exportFilter':
count=this.filterExportList();
var panel=this.$('exportFilterPanel');
if (count==-1) { panel.style.display='block'; break; }
this.$('exportStart').disabled=(count==0);
this.$('exportDelete').disabled=(count==0);
this.displayStatus(count,total);
if (count==0) { alert('No tiddlers were selected'); panel.style.display='block'; }
break;
case 'exportStart':
this.go();
break;
case 'exportDelete':
this.deleteTiddlers();
break;
case 'exportHideFilter':
case 'exportToggleFilter':
var panel=this.$('exportFilterPanel')
panel.style.display=(panel.style.display=='block')?'none':'block';
break;
case 'exportSelectChanges':
var lastmod=new Date(document.lastModified);
for (var t = 0; t < theList.options.length; t++) {
if (theList.options[t].value=='') continue;
var tiddler=store.getTiddler(theList.options[t].value); if (!tiddler) continue;
theList.options[t].selected=(tiddler.modified>lastmod);
count += (tiddler.modified>lastmod)?1:0;
}
this.$('exportStart').disabled=(count==0);
this.$('exportDelete').disabled=(count==0);
this.displayStatus(count,total);
if (count==0) alert('There are no unsaved changes');
break;
case 'exportSelectAll':
for (var t = 0; t < theList.options.length; t++) {
if (theList.options[t].value=='') continue;
theList.options[t].selected=true;
count += 1;
}
this.$('exportStart').disabled=(count==0);
this.$('exportDelete').disabled=(count==0);
this.displayStatus(count,count);
break;
case 'exportSelectOpened':
for (var t=0; t<theList.options.length; t++) theList.options[t].selected=false;
var tiddlerDisplay=this.$('tiddlerDisplay');
for (var t=0; t<tiddlerDisplay.childNodes.length;t++) {
var tiddler=tiddlerDisplay.childNodes[t].id.substr(7);
for (var i=0; i<theList.options.length; i++) {
if (theList.options[i].value!=tiddler) continue;
theList.options[i].selected=true; count++; break;
}
}
this.$('exportStart').disabled=(count==0);
this.$('exportDelete').disabled=(count==0);
this.displayStatus(count,total);
if (count==0) alert('There are no tiddlers currently opened');
break;
case 'exportSelectRelated':
// recursively build list of related tiddlers
function getRelatedTiddlers(tid,tids) {
var t=store.getTiddler(tid); if (!t || tids.contains(tid)) return tids;
tids.push(t.title);
if (!t.linksUpdated) t.changed();
for (var i=0; i<t.links.length; i++)
if (t.links[i]!=tid) tids=getRelatedTiddlers(t.links[i],tids);
return tids;
}
// for all currently selected tiddlers, gather up the related tiddlers (including self) and select them as well
var tids=[];
for (var i=0; i<theList.options.length; i++)
if (theList.options[i].selected) tids=getRelatedTiddlers(theList.options[i].value,tids);
// select related tiddlers (includes original selected tiddlers)
for (var i=0; i<theList.options.length; i++)
theList.options[i].selected=tids.contains(theList.options[i].value);
this.displayStatus(tids.length,total);
break;
case 'exportListSmaller': // decrease current listbox size
var min=5;
theList.size-=(theList.size>min)?1:0;
break;
case 'exportListLarger': // increase current listbox size
var max=(theList.options.length>25)?theList.options.length:25;
theList.size+=(theList.size<max)?1:0;
break;
case 'exportClose':
this.$('exportPanel').style.display='none';
break;
}
return false;
},
displayStatus: function(count,total) {
var txt=this.statusmsg.format([total,total!=1?'s':'',!count?'none':count==total?'all':count]);
clearMessage(); displayMessage(txt);
return txt;
},
refreshList: function(selectedIndex) {
var theList = this.$('exportList'); if (!theList) return;
// get the sort order
var sort;
if (!selectedIndex) selectedIndex=0;
if (selectedIndex==0) sort='modified';
if (selectedIndex==1) sort='title';
if (selectedIndex==2) sort='modified';
if (selectedIndex==3) sort='modifier';
if (selectedIndex==4) sort='tags';
// unselect headings and count number of tiddlers actually selected
var count=0;
for (var t=5; t < theList.options.length; t++) {
if (!theList.options[t].selected) continue;
if (theList.options[t].value!='')
count++;
else { // if heading is selected, deselect it, and then select and count all in section
theList.options[t].selected=false;
for ( t++; t<theList.options.length && theList.options[t].value!=''; t++) {
theList.options[t].selected=true;
count++;
}
}
}
// disable 'export' and 'delete' buttons if no tiddlers selected
this.$('exportStart').disabled=(count==0);
this.$('exportDelete').disabled=(count==0);
// show selection count
var tiddlers = store.getTiddlers('title');
if (theList.options.length) this.displayStatus(count,tiddlers.length);
// if a [command] item, reload list... otherwise, no further refresh needed
if (selectedIndex>4) return;
// clear current list contents
while (theList.length > 0) { theList.options[0] = null; }
// add heading and control items to list
var i=0;
var indent=String.fromCharCode(160)+String.fromCharCode(160);
theList.options[i++]=
new Option(tiddlers.length+' tiddlers in document', '',false,false);
theList.options[i++]=
new Option(((sort=='title' )?'>':indent)+' [by title]', '',false,false);
theList.options[i++]=
new Option(((sort=='modified')?'>':indent)+' [by date]', '',false,false);
theList.options[i++]=
new Option(((sort=='modifier')?'>':indent)+' [by author]', '',false,false);
theList.options[i++]=
new Option(((sort=='tags' )?'>':indent)+' [by tags]', '',false,false);
// output the tiddler list
switch(sort) {
case 'title':
for(var t = 0; t < tiddlers.length; t++)
theList.options[i++] = new Option(tiddlers[t].title,tiddlers[t].title,false,false);
break;
case 'modifier':
case 'modified':
var tiddlers = store.getTiddlers(sort);
// sort descending for newest date first
tiddlers.sort(function (a,b) {if(a[sort] == b[sort]) return(0); else return (a[sort] > b[sort]) ? -1 : +1; });
var lastSection = '';
for(var t = 0; t < tiddlers.length; t++) {
var tiddler = tiddlers[t];
var theSection = '';
if (sort=='modified') theSection=tiddler.modified.toLocaleDateString();
if (sort=='modifier') theSection=tiddler.modifier;
if (theSection != lastSection) {
theList.options[i++] = new Option(theSection,'',false,false);
lastSection = theSection;
}
theList.options[i++] = new Option(indent+indent+tiddler.title,tiddler.title,false,false);
}
break;
case 'tags':
var theTitles = {}; // all tiddler titles, hash indexed by tag value
var theTags = new Array();
for(var t=0; t<tiddlers.length; t++) {
var title=tiddlers[t].title;
var tags=tiddlers[t].tags;
if (!tags || !tags.length) {
if (theTitles['untagged']==undefined) { theTags.push('untagged'); theTitles['untagged']=new Array(); }
theTitles['untagged'].push(title);
}
else for(var s=0; s<tags.length; s++) {
if (theTitles[tags[s]]==undefined) { theTags.push(tags[s]); theTitles[tags[s]]=new Array(); }
theTitles[tags[s]].push(title);
}
}
theTags.sort();
for(var tagindex=0; tagindex<theTags.length; tagindex++) {
var theTag=theTags[tagindex];
theList.options[i++]=new Option(theTag,'',false,false);
for(var t=0; t<theTitles[theTag].length; t++)
theList.options[i++]=new Option(indent+indent+theTitles[theTag][t],theTitles[theTag][t],false,false);
}
break;
}
theList.selectedIndex=selectedIndex; // select current control item
this.$('exportStart').disabled=true;
this.$('exportDelete').disabled=true;
this.displayStatus(0,tiddlers.length);
},
askForFilename: function(here) {
var msg=here.title; // use tooltip as dialog box message
var path=getLocalPath(document.location.href);
var slashpos=path.lastIndexOf('/'); if (slashpos==-1) slashpos=path.lastIndexOf('\\');
if (slashpos!=-1) path = path.substr(0,slashpos+1); // remove filename from path, leave the trailing slash
var filetype=this.$('exportFormat').value.toLowerCase();
var defext='html';
if (filetype==this.type_TX) defext='txt';
if (filetype==this.type_CS) defext='csv';
if (filetype==this.type_NF) defext='xml';
var file=this.newdefault.replace(/html$/,defext);
var result='';
if(window.Components) { // moz
try {
netscape.security.PrivilegeManager.enablePrivilege('UniversalXPConnect');
var nsIFilePicker = window.Components.interfaces.nsIFilePicker;
var picker = Components.classes['@mozilla.org/filepicker;1'].createInstance(nsIFilePicker);
picker.init(window, msg, nsIFilePicker.modeSave);
var thispath = Components.classes['@mozilla.org/file/local;1'].createInstance(Components.interfaces.nsILocalFile);
thispath.initWithPath(path);
picker.displayDirectory=thispath;
picker.defaultExtension=defext;
picker.defaultString=file;
picker.appendFilters(nsIFilePicker.filterAll|nsIFilePicker.filterText|nsIFilePicker.filterHTML);
if (picker.show()!=nsIFilePicker.returnCancel) var result=picker.file.path;
}
catch(e) { alert('error during local file access: '+e.toString()) }
}
else { // IE
try { // XPSP2 IE only
var s = new ActiveXObject('UserAccounts.CommonDialog');
s.Filter='All files|*.*|Text files|*.txt|HTML files|*.htm;*.html|XML files|*.xml|';
s.FilterIndex=defext=='txt'?2:'html'?3:'xml'?4:1;
s.InitialDir=path;
s.FileName=file;
if (s.showOpen()) var result=s.FileName;
}
catch(e) { // fallback
var result=prompt(msg,path+file);
}
}
return result;
},
initFilter: function() {
this.$('exportFilterStart').checked=false; this.$('exportStartDate').value='';
this.$('exportFilterEnd').checked=false; this.$('exportEndDate').value='';
this.$('exportFilterTags').checked=false; this.$('exportTags').value='';
this.$('exportFilterText').checked=false; this.$('exportText').value='';
this.showFilterFields();
},
showFilterFields: function(which) {
var show=this.$('exportFilterStart').checked;
this.$('exportFilterStartBy').style.display=show?'block':'none';
this.$('exportStartDate').style.display=show?'block':'none';
var val=this.$('exportFilterStartBy').value;
this.$('exportStartDate').value
=this.getFilterDate(val,'exportStartDate').formatString(this.datetimefmt);
if (which && (which.id=='exportFilterStartBy') && (val=='other'))
this.$('exportStartDate').focus();
var show=this.$('exportFilterEnd').checked;
this.$('exportFilterEndBy').style.display=show?'block':'none';
this.$('exportEndDate').style.display=show?'block':'none';
var val=this.$('exportFilterEndBy').value;
this.$('exportEndDate').value
=this.getFilterDate(val,'exportEndDate').formatString(this.datetimefmt);
if (which && (which.id=='exportFilterEndBy') && (val=='other'))
this.$('exportEndDate').focus();
var show=this.$('exportFilterTags').checked;
this.$('exportTags').style.display=show?'block':'none';
var show=this.$('exportFilterText').checked;
this.$('exportText').style.display=show?'block':'none';
},
getFilterDate: function(val,id) {
var result=0;
switch (val) {
case 'file':
result=new Date(document.lastModified);
break;
case 'other':
result=new Date(this.$(id).value);
break;
default: // today=0, yesterday=1, one week=7, two weeks=14, a month=31
var now=new Date(); var tz=now.getTimezoneOffset()*60000; now-=tz;
var oneday=86400000;
if (id=='exportStartDate')
result=new Date((Math.floor(now/oneday)-val)*oneday+tz);
else
result=new Date((Math.floor(now/oneday)-val+1)*oneday+tz-1);
break;
}
return result;
},
filterExportList: function() {
var theList = this.$('exportList'); if (!theList) return -1;
var filterStart=this.$('exportFilterStart').checked;
var val=this.$('exportFilterStartBy').value;
var startDate=config.macros.exportTiddlers.getFilterDate(val,'exportStartDate');
var filterEnd=this.$('exportFilterEnd').checked;
var val=this.$('exportFilterEndBy').value;
var endDate=config.macros.exportTiddlers.getFilterDate(val,'exportEndDate');
var filterTags=this.$('exportFilterTags').checked;
var tags=this.$('exportTags').value;
var filterText=this.$('exportFilterText').checked;
var text=this.$('exportText').value;
if (!(filterStart||filterEnd||filterTags||filterText)) {
alert('Please set the selection filter');
this.$('exportFilterPanel').style.display='block';
return -1;
}
if (filterStart&&filterEnd&&(startDate>endDate)) {
var msg='starting date/time:\n'
msg+=startDate.toLocaleString()+'\n';
msg+='is later than ending date/time:\n'
msg+=endDate.toLocaleString()
alert(msg);
return -1;
}
// if filter by tags, get list of matching tiddlers
// use getMatchingTiddlers() (if MatchTagsPlugin is installed) for full boolean expressions
// otherwise use getTaggedTiddlers() for simple tag matching
if (filterTags) {
var fn=store.getMatchingTiddlers||store.getTaggedTiddlers;
var t=fn.apply(store,[tags]);
var tagged=[];
for (var i=0; i<t.length; i++) tagged.push(t[i].title);
}
// scan list and select tiddlers that match all applicable criteria
var total=0;
var count=0;
for (var i=0; i<theList.options.length; i++) {
// get item, skip non-tiddler list items (section headings)
var opt=theList.options[i]; if (opt.value=='') continue;
// get tiddler, skip missing tiddlers (this should NOT happen)
var tiddler=store.getTiddler(opt.value); if (!tiddler) continue;
var sel=true;
if ( (filterStart && tiddler.modified<startDate)
|| (filterEnd && tiddler.modified>endDate)
|| (filterTags && !tagged.contains(tiddler.title))
|| (filterText && (tiddler.text.indexOf(text)==-1) && (tiddler.title.indexOf(text)==-1)))
sel=false;
opt.selected=sel;
count+=sel?1:0;
total++;
}
return count;
},
deleteTiddlers: function() {
var list=this.$('exportList'); if (!list) return;
var tids=[];
for (i=0;i<list.length;i++)
if (list.options[i].selected && list.options[i].value.length)
tids.push(list.options[i].value);
if (!confirm('Are you sure you want to delete these tiddlers:\n\n'+tids.join(', '))) return;
store.suspendNotifications();
for (t=0;t<tids.length;t++) {
var tid=store.getTiddler(tids[t]); if (!tid) continue;
var msg="'"+tid.title+"' is tagged with 'systemConfig'.\n\n";
msg+='Removing this tiddler may cause unexpected results. Are you sure?'
if (tid.tags.contains('systemConfig') && !confirm(msg)) continue;
store.removeTiddler(tid.title);
story.closeTiddler(tid.title);
}
store.resumeNotifications();
alert(tids.length+' tiddlers deleted');
this.refreshList(0); // reload listbox
store.notifyAll(); // update page display
},
go: function() {
if (window.location.protocol!='file:') // make sure we are local
{ displayMessage(config.messages.notFileUrlError); return; }
// get selected tidders, target filename, target type, and notes
var list=this.$('exportList'); if (!list) return;
var tids=[]; for (var i=0; i<list.options.length; i++) {
var opt=list.options[i]; if (!opt.selected||!opt.value.length) continue;
var tid=store.getTiddler(opt.value); if (!tid) continue;
tids.push(tid);
}
if (!tids.length) return; // no tiddlers selected
var target=this.$('exportFilename').value.trim();
if (!target.length) {
displayMessage('A local target path/filename is required',target);
return;
}
var merge=this.$('exportMerge').checked;
var filetype=this.$('exportFormat').value.toLowerCase();
var notes=this.$('exportNotes').value.replace(/\n/g,'<br>');
var total={val:0};
var out=this.assembleFile(target,filetype,tids,notes,total,merge);
if (!total.val) return; // cancelled file overwrite
var link='file:///'+target.replace(/\\/g,'/');
var samefile=link==decodeURIComponent(window.location.href);
var p=getLocalPath(document.location.href);
if (samefile) {
if (config.options.chkSaveBackups) { var t=loadOriginal(p);if(t)saveBackup(p,t); }
if (config.options.chkGenerateAnRssFeed && saveRss instanceof Function) saveRss(p);
}
var ok=saveFile(target,out);
displayMessage((ok?this.okmsg:this.failmsg).format([total.val,total.val!=1?'s':'',target]),link);
},
plainTextHeader:
'Source:\n\t%0\n'
+'Title:\n\t%1\n'
+'Subtitle:\n\t%2\n'
+'Created:\n\t%3 by %4\n'
+'Application:\n\tTiddlyWiki %5 / %6 %7\n\n',
plainTextTiddler:
'- - - - - - - - - - - - - - -\n'
+'| title: %0\n'
+'| created: %1\n'
+'| modified: %2\n'
+'| edited by: %3\n'
+'| tags: %4\n'
+'- - - - - - - - - - - - - - -\n'
+'%5\n',
plainTextFooter:
'',
newsFeedHeader:
'<'+'?xml version="1.0"?'+'>\n'
+'<rss version="2.0">\n'
+'<channel>\n'
+'<title>%1</title>\n'
+'<link>%0</link>\n'
+'<description>%2</description>\n'
+'<language>en-us</language>\n'
+'<copyright>Copyright '+(new Date().getFullYear())+' %4</copyright>\n'
+'<pubDate>%3</pubDate>\n'
+'<lastBuildDate>%3</lastBuildDate>\n'
+'<docs>http://blogs.law.harvard.edu/tech/rss</docs>\n'
+'<generator>TiddlyWiki %5 / %6 %7</generator>\n',
newsFeedTiddler:
'\n%0\n',
newsFeedFooter:
'</channel></rss>',
pureStoreHeader:
'<html><body>'
+'<style type="text/css">'
+' #storeArea {display:block;margin:1em;}'
+' #storeArea div {padding:0.5em;margin:1em;border:2px solid black;height:10em;overflow:auto;}'
+' #pureStoreHeading {width:100%;text-align:left;background-color:#eeeeee;padding:1em;}'
+'</style>'
+'<div id="pureStoreHeading">'
+' TiddlyWiki "PureStore" export file<br>'
+' Source'+': <b>%0</b><br>'
+' Title: <b>%1</b><br>'
+' Subtitle: <b>%2</b><br>'
+' Created: <b>%3</b> by <b>%4</b><br>'
+' TiddlyWiki %5 / %6 %7<br>'
+' Notes:<hr><pre>%8</pre>'
+'</div>'
+'<div id="storeArea">',
pureStoreTiddler:
'%0\n%1',
pureStoreFooter:
'</div><!--POST-BODY-START-->\n<!--POST-BODY-END--></body></html>',
assembleFile: function(target,filetype,tids,notes,total,merge) {
var revised='';
var now = new Date().toLocaleString();
var src=convertUnicodeToUTF8(document.location.href);
var title = convertUnicodeToUTF8(wikifyPlain('SiteTitle').htmlEncode());
var subtitle = convertUnicodeToUTF8(wikifyPlain('SiteSubtitle').htmlEncode());
var user = convertUnicodeToUTF8(config.options.txtUserName.htmlEncode());
var twver = version.major+'.'+version.minor+'.'+version.revision;
var v=version.extensions.ExportTiddlersPlugin; var pver = v.major+'.'+v.minor+'.'+v.revision;
var headerargs=[src,title,subtitle,now,user,twver,'ExportTiddlersPlugin',pver,notes];
switch (filetype) {
case this.type_TX: // plain text
var header=this.plainTextHeader.format(headerargs);
var footer=this.plainTextFooter;
break;
case this.type_CS: // comma-separated
var fields={};
for (var i=0; i<tids.length; i++) for (var f in tids[i].fields) fields[f]=f;
var names=['title','created','modified','modifier','tags','text'];
for (var f in fields) names.push(f);
var header=names.join(',')+'\n';
var footer='';
break;
case this.type_NF: // news feed (XML)
headerargs[0]=store.getTiddlerText('SiteUrl','');
var header=this.newsFeedHeader.format(headerargs);
var footer=this.newsFeedFooter;
break;
case this.type_PS: // PureStore (no code)
var header=this.pureStoreHeader.format(headerargs);
var footer=this.pureStoreFooter;
break;
case this.type_TW: // full TiddlyWiki
default:
var currPath=getLocalPath(window.location.href);
var original=loadFile(currPath);
if (!original) { displayMessage(config.messages.cantSaveError); return; }
var posDiv = locateStoreArea(original);
if (!posDiv) { displayMessage(config.messages.invalidFileError.format([currPath])); return; }
var header = original.substr(0,posDiv[0]+startSaveArea.length)+'\n';
var footer = '\n'+original.substr(posDiv[1]);
break;
}
var out=this.getData(target,filetype,tids,fields,merge);
var revised = header+convertUnicodeToUTF8(out.join('\n'))+footer;
// if full TW, insert page title and language attr, and reset all MARKUP blocks...
if (filetype==this.type_TW) {
var newSiteTitle=convertUnicodeToUTF8(getPageTitle()).htmlEncode();
revised=revised.replaceChunk('<title'+'>','</title'+'>',' ' + newSiteTitle + ' ');
revised=updateLanguageAttribute(revised);
var titles=[]; for (var i=0; i<tids.length; i++) titles.push(tids[i].title);
revised=updateMarkupBlock(revised,'PRE-HEAD',
titles.contains('MarkupPreHead')? 'MarkupPreHead' :null);
revised=updateMarkupBlock(revised,'POST-HEAD',
titles.contains('MarkupPostHead')?'MarkupPostHead':null);
revised=updateMarkupBlock(revised,'PRE-BODY',
titles.contains('MarkupPreBody')? 'MarkupPreBody' :null);
revised=updateMarkupBlock(revised,'POST-SCRIPT',
titles.contains('MarkupPostBody')?'MarkupPostBody':null);
}
total.val=out.length;
return revised;
},
getData: function(target,filetype,tids,fields,merge) {
// output selected tiddlers and gather list of titles (for use with merge)
var out=[]; var titles=[];
var url=store.getTiddlerText('SiteUrl','');
for (var i=0; i<tids.length; i++) {
out.push(this.formatItem(store,filetype,tids[i],url,fields));
titles.push(tids[i].title);
}
// if TW or PureStore format, ask to merge with existing tiddlers (if any)
if (filetype==this.type_TW || filetype==this.type_PS) {
var txt=loadFile(target);
if (txt && txt.length) {
var remoteStore=new TiddlyWiki();
if (version.major+version.minor*.1+version.revision*.01<2.52) txt=convertUTF8ToUnicode(txt);
if (remoteStore.importTiddlyWiki(txt)) {
var existing=remoteStore.getTiddlers('title');
var msg=this.overwriteprompt.format([target,existing.length,existing.length!=1?'s':'']);
if (merge) {
var added=titles.length; var updated=0; var kept=0;
for (var i=0; i<existing.length; i++)
if (titles.contains(existing[i].title)) {
added--; updated++;
} else {
out.push(this.formatItem(remoteStore,filetype,existing[i],url));
kept++;
}
displayMessage(this.mergestatus.format(
[added,added!=1?'s':'',updated,updated!=1?'s':'',kept,kept!=1?'s':'',]));
}
else if (!confirm(msg)) out=[]; // empty the list = don't write file
}
}
}
return out;
},
formatItem: function(s,f,t,u,fields) {
if (f==this.type_TW)
var r=s.getSaver().externalizeTiddler(s,t);
if (f==this.type_PS)
var r=this.pureStoreTiddler.format([t.title,s.getSaver().externalizeTiddler(s,t)]);
if (f==this.type_NF)
var r=this.newsFeedTiddler.format([t.saveToRss(u)]);
if (f==this.type_TX)
var r=this.plainTextTiddler.format([t.title, t.created.toLocaleString(), t.modified.toLocaleString(),
t.modifier, String.encodeTiddlyLinkList(t.tags), t.text]);
if (f==this.type_CS) {
function toCSV(t) { return '"'+t.replace(/"/g,'""')+'"'; } // always encode CSV
var out=[ toCSV(t.title), toCSV(t.created.toLocaleString()), toCSV(t.modified.toLocaleString()),
toCSV(t.modifier), toCSV(String.encodeTiddlyLinkList(t.tags)), toCSV(t.text) ];
for (var f in fields) out.push(toCSV(t.fields[f]||''));
var r=out.join(',');
}
return r||"";
}
}
//}}}
/***
!!!Control panel CSS
//{{{
!css
#exportPanel {
display: none; position:absolute; z-index:12; width:35em; right:105%; top:6em;
background-color: #eee; color:#000; font-size: 8pt; line-height:110%;
border:1px solid black; border-bottom-width: 3px; border-right-width: 3px;
padding: 0.5em; margin:0em; -moz-border-radius:1em;-webkit-border-radius:1em;
}
#exportPanel a, #exportPanel td a { color:#009; display:inline; margin:0px; padding:1px; }
#exportPanel table {
width:100%; border:0px; padding:0px; margin:0px;
font-size:8pt; line-height:110%; background:transparent;
}
#exportPanel tr { border:0px;padding:0px;margin:0px; background:transparent; }
#exportPanel td { color:#000; border:0px;padding:0px;margin:0px; background:transparent; }
#exportPanel select { width:98%;margin:0px;font-size:8pt;line-height:110%;}
#exportPanel input { width:98%;padding:0px;margin:0px;font-size:8pt;line-height:110%; }
#exportPanel textarea { width:98%;padding:0px;margin:0px;overflow:auto;font-size:8pt; }
#exportPanel .box {
border:1px solid black; padding:3px; margin-bottom:5px;
background:#f8f8f8; -moz-border-radius:5px;-webkit-border-radius:5px; }
#exportPanel .topline { border-top:2px solid black; padding-top:3px; margin-bottom:5px; }
#exportPanel .rad { width:auto;border:0 }
#exportPanel .chk { width:auto;border:0 }
#exportPanel .btn { width:auto; }
#exportPanel .btn1 { width:98%; }
#exportPanel .btn2 { width:48%; }
#exportPanel .btn3 { width:32%; }
#exportPanel .btn4 { width:24%; }
#exportPanel .btn5 { width:19%; }
!end
//}}}
!!!Control panel HTML
//{{{
!html
<!-- target path/file -->
<div>
<div style="float:right;padding-right:.5em">
<input type="checkbox" style="width:auto" id="exportMerge" CHECKED
title="combine selected tiddlers with existing tiddlers (if any) in export file"> merge
</div>
export to:<br>
<input type="text" id="exportFilename" size=40 style="width:93%"><input
type="button" id="exportBrowse" value="..." title="select or enter a local folder/file..." style="width:5%"
onclick="var fn=config.macros.exportTiddlers.askForFilename(this); if (fn.length) this.previousSibling.value=fn; ">
</div>
<!-- output format -->
<div>
format:
<select id="exportFormat" size=1>
<option value="TW">TiddlyWiki HTML document (includes core code)</option>
<option value="PS">TiddlyWiki "PureStore" HTML file (tiddler data only)</option>
<option value="TX">TiddlyWiki plain text TXT file (tiddler source listing)</option>
<option value="CS">Comma-Separated Value (CSV) data file</option>
<option value="NF">RSS NewsFeed XML file</option>
</select>
</div>
<!-- notes -->
<div>
notes:<br>
<textarea id="exportNotes" rows=3 cols=40 style="height:4em;margin-bottom:5px;" onfocus="this.select()"></textarea>
</div>
<!-- list of tiddlers -->
<table><tr align="left"><td>
select:
<a href="JavaScript:;" id="exportSelectAll"
onclick="return config.macros.exportTiddlers.process(this)" title="select all tiddlers">
all </a>
<a href="JavaScript:;" id="exportSelectChanges"
onclick="return config.macros.exportTiddlers.process(this)" title="select tiddlers changed since last save">
changes </a>
<a href="JavaScript:;" id="exportSelectOpened"
onclick="return config.macros.exportTiddlers.process(this)" title="select tiddlers currently being displayed">
opened </a>
<a href="JavaScript:;" id="exportSelectRelated"
onclick="return config.macros.exportTiddlers.process(this)" title="select tiddlers related to the currently selected tiddlers">
related </a>
<a href="JavaScript:;" id="exportToggleFilter"
onclick="return config.macros.exportTiddlers.process(this)" title="show/hide selection filter">
filter </a>
</td><td align="right">
<a href="JavaScript:;" id="exportListSmaller"
onclick="return config.macros.exportTiddlers.process(this)" title="reduce list size">
– </a>
<a href="JavaScript:;" id="exportListLarger"
onclick="return config.macros.exportTiddlers.process(this)" title="increase list size">
+ </a>
</td></tr></table>
<select id="exportList" multiple size="10" style="margin-bottom:5px;"
onchange="config.macros.exportTiddlers.refreshList(this.selectedIndex)">
</select><br>
<!-- selection filter -->
<div id="exportFilterPanel" style="display:none">
<table><tr align="left"><td>
selection filter
</td><td align="right">
<a href="JavaScript:;" id="exportHideFilter"
onclick="return config.macros.exportTiddlers.process(this)" title="hide selection filter">hide</a>
</td></tr></table>
<div class="box">
<input type="checkbox" class="chk" id="exportFilterStart" value="1"
onclick="config.macros.exportTiddlers.showFilterFields(this)"> starting date/time<br>
<table cellpadding="0" cellspacing="0"><tr valign="center"><td width="50%">
<select size=1 id="exportFilterStartBy"
onchange="config.macros.exportTiddlers.showFilterFields(this);">
<option value="0">today</option>
<option value="1">yesterday</option>
<option value="7">a week ago</option>
<option value="30">a month ago</option>
<option value="file">file date</option>
<option value="other">other (mm/dd/yyyy hh:mm)</option>
</select>
</td><td width="50%">
<input type="text" id="exportStartDate" onfocus="this.select()"
onchange="config.macros.exportTiddlers.$('exportFilterStartBy').value='other';">
</td></tr></table>
<input type="checkbox" class="chk" id="exportFilterEnd" value="1"
onclick="config.macros.exportTiddlers.showFilterFields(this)"> ending date/time<br>
<table cellpadding="0" cellspacing="0"><tr valign="center"><td width="50%">
<select size=1 id="exportFilterEndBy"
onchange="config.macros.exportTiddlers.showFilterFields(this);">
<option value="0">today</option>
<option value="1">yesterday</option>
<option value="7">a week ago</option>
<option value="30">a month ago</option>
<option value="file">file date</option>
<option value="other">other (mm/dd/yyyy hh:mm)</option>
</select>
</td><td width="50%">
<input type="text" id="exportEndDate" onfocus="this.select()"
onchange="config.macros.exportTiddlers.$('exportFilterEndBy').value='other';">
</td></tr></table>
<input type="checkbox" class="chk" id=exportFilterTags value="1"
onclick="config.macros.exportTiddlers.showFilterFields(this)"> match tags<br>
<input type="text" id="exportTags" onfocus="this.select()">
<input type="checkbox" class="chk" id=exportFilterText value="1"
onclick="config.macros.exportTiddlers.showFilterFields(this)"> match titles/tiddler text<br>
<input type="text" id="exportText" onfocus="this.select()">
</div> <!--box-->
</div> <!--panel-->
<!-- action buttons -->
<div style="text-align:center">
<input type=button class="btn4" onclick="config.macros.exportTiddlers.process(this)"
id="exportFilter" value="apply filter">
<input type=button class="btn4" onclick="config.macros.exportTiddlers.process(this)"
id="exportStart" value="export tiddlers">
<input type=button class="btn4" onclick="config.macros.exportTiddlers.process(this)"
id="exportDelete" value="delete tiddlers">
<input type=button class="btn4" onclick="config.macros.exportTiddlers.process(this)"
id="exportClose" value="close">
</div><!--center-->
!end
//}}}
***/
/***
|Name|ExportTiddlersPluginInfo|
|Source|http://www.TiddlyTools.com/#ExportTiddlersPlugin|
|Documentation|http://www.TiddlyTools.com/#ExportTiddlersPluginInfo|
|Version|2.9.5|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|Documentation for ExportTiddlersPlugin|
interactively select and extract tiddlers from your ~TiddlyWiki document, and write them into another file, using one of several different file formats:
* ~TiddlyWiki - a complete, stand-alone, standard TiddlyWiki HTML document
* ~PureStore - a small HTML archive file containing tiddler data only (no core code)
* ~PlainText - a simple TXT text file with tiddler source listings
* Comma - a "Comma Separated Value" data/spreadsheet file
* ~NewsFeed - an XML-format file that can be published for RSS syndication.
!!!!!Usage
<<<
{{{
<<exportTiddlers>> (sidebar menu item)
<<exportTiddlers inline>> (embedded control panel)
}}}
Inline control panel (live):
<<exportTiddlers inline>>
Optional "special tiddlers" used by this plugin:
* SiteUrl<br>URL for official server-published version of document being viewed (used in XML export). Default: //none//
<<<
!!!!!Revisions
<<<
2010.02.25 2.9.5 added merge checkbox option and improved 'merge' status message
2009.09.12 2.9.4 fixed 'return false' to prevent IE page transitions
2009.07.06 2.9.3 moved HTML to section for size reduction
2009.07.03 2.9.2 TW252 fixup: don't call convertUTF8ToUnicode() for local loadFile() I/O
2009.04.30 2.9.1 custom fields in CSV output
2009.04.19 2.9.0 added CSV format
2009.02.26 2.8.5 use macro-specific definition of $() function abbreviation (avoids conflict with JQuery)
2008.09.29 2.8.4 in getData(), convert existing TW file from UTF8 to Unicode before merging to correct handling of international characters and symbols.
2008.09.26 2.8.3 in go(), if rewriting *current* file and chkSaveBackups and/or chkGenerateAnRssFeed is enabled, then write a backup file or RSS feed, respectively.
2008.09.24 2.8.2 in assembleFile(), make sure that markup block is updated if corresponding Markup* tiddler is exported.
2008.09.19 2.8.1 in formatItem(), removed unnecessary convertUnicodeToUTF8() (was causing double-conversion!)
2008.09.11 2.8.0 extensive code cleanup: moved all global functions inside macro object. Re-wrote file generator and I/O to support TiddlyWiki, PlainText, PureStore, and NewsFeed file formats. Replaced inline 'match tags' code with use of getMatchingTiddlers() from [[MatchTagsPlugin]] (if installed), with fallback to core getTaggedTiddlers() otherwise.
2008.05.27 2.7.0 added ability to 'merge' with existing export file. Also, revised 'matchTags' functionality to be more robust and more efficient
2008.05.12 2.6.1 automatically add 'export' task to backstage (moved from BackstageTweaks)
2008.03.10 2.6.0 added "delete tiddlers" button
2007.12.04 *.*.* update for TW2.3.0: replaced deprecated core functions, regexps, and macros
2007.11.10 2.5.1 removed debugging alert messages from promptForExportFilename()
2007.10.31 2.5.0 code reduction: removed incomplete/unused interface and supporting functions for exporting directly to http, https or ftp servers. Plugin now supports exporting to local file only. Also, updated TW document output to generate TW2.2 compatible file format.
2007.10.30 2.4.2 added automatic shadow tiddler definition for [[ExportTiddlers]]
2007.07.16 2.4.1 in exportTWHeader(), reset HTML source 'markup' so installed markup is NOT copied to new file.
2007.06.30 2.4.0 added "select related tiddlers" feature. Recursively scans the tiddler links[] info to find all tiddlers referenced by any of the currently selected tiddler, and then selects them all (including the original tiddlers).
2007.04.19 2.3.0 in exportData(), pass SiteURL value as param to saveToRss(). Fixes 'undefined' appearing in tiddler link in XML output. Also, in refreshExportList(), added 'sort by tags'. Also, added 'group select'... selecting a heading (date,author,tag) auto-selects all tiddlers in that group.
2007.03.02 2.2.6 in onClickExportButton(), when selecting open tiddlers for TW2.2, look for "storyDisplay" with fallback to "tiddlerDisplay" for TW2.1 or earlier
2007.03.01 2.2.5 removed hijack of store.saveChanges()
2006.11.08 2.2.4 added promptForExportFilename() and replaced type="file" control with edit field + browse button ("...").
2006.10.12 2.2.3 in exportDIVFooter(), write POST-BODY-START/END markers for compatibility with TW2.1 core file format.
2006.05.11 2.2.2 in createExportPanel, removed call to addNotification() to reduce unneeded feedback messages and increase overall document performance.
2006.05.02 2.2.1 Use displayMessage() to show number of selected tiddlers instead of updating listbox 'header' item after each selection. Prevents awkward 'scroll-to-top' behavior that made multi-select via ctrl-click nearly impossible.
2006.04.29 2.2.0 New features: free-form "Notes" text inserted in the header of PureStore files.
2006.03.29 2.1.3 added calls to convertUnicodeToUTF8() for generated output, so it better handles international characters.
2006.02.12 2.1.2 more FF1501 bug fixes.
2006.02.04 2.1.1 added var to unintended globals to avoids FireFox1501 crash bug
2006.02.02 2.1.0 Added support for output of complete TiddlyWiki documents
2006.01.21 2.0.1 Defer initial panel creation and only register a notification function when panel first is created
in saveChanges 'hijack', create panel as needed. Note: if window.event is not available to identify the click location, the export panel is positioned relative to the 'tiddlerDisplay' element of the TW document.
2005.12.27 2.0.0 Update for TW2.0.
2005.12.24 0.9.5 Minor adjustments to CSS to force correct link colors regardless of TW stylesheet selection
2005.12.16 0.9.4 Dynamically create/remove exportPanel so only one instance exists at a time
2005.11.15 0.9.2 added non-Ajax post to bypass cross-domain security restrictions.
2005.11.08 0.9.1 moved HTML, CSS and control initialization into exportInit() function and call from macro handler instead of at load time.
2005.10.28 0.9.0 added 'select opened tiddlers' feature. Based on a suggestion by Geoff Slocock
2005.10.24 0.8.3 Corrected hijack of 'save changes' when using http:
2005.10.18 0.8.2 added AJAX functions
2005.10.18 0.8.1 Corrected timezone handling and error checking/reporting when filtering tiddlers. More style tweaks, minor text changes and some assorted layout cleanup.
2005.10.17 0.8.0 First pre-release.
2005.10.16 0.7.0 filter by tags
2005.10.15 0.6.0 filter by title/text
2005.10.14 0.5.0 export to local file (DIV or XML)
2005.10.14 0.4.0 filter by start/end date
2005.10.13 0.3.0 panel interaction
2005.10.11 0.2.0 panel layout
2005.10.10 0.1.0 code framework
2005.10.09 0.0.0 development started
<<<
/***
|Name|ExternalTiddlersPlugin|
|Source|http://www.TiddlyTools.com/#ExternalTiddlersPlugin|
|Documentation|http://www.TiddlyTools.com/#ExternalTiddlersPluginInfo|
|Version|1.3.2|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Requires|TemporaryTiddlersPlugin, SectionLinksPlugin (optional, recommended)|
|Description|retrieve and wikify content from external files or remote URLs|
This plugin extends the {{{<<tiddler>>}}} macro syntax so you can retrieve and wikify content directly from external files or remote URLs. You can also define alternative "fallback" sources to provide basic "import on demand" handling by automatically creating/importing tiddler content from external sources when the specified ~TiddlerName does not already exist in your document.
!!!!!Documentation
>see [[ExternalTiddlersPluginInfo]]
!!!!!Configuration
<<<
<<option chkExternalTiddlersImport>> automatically create/import tiddlers when using external fallback references
{{{usage: <<option chkExternalTiddlersImport>>}}}
<<option chkExternalTiddlersQuiet>> don't display messages when adding tiddlers ("quiet mode")
{{{usage: <<option chkExternalTiddlersQuiet>>}}}
<<option chkExternalTiddlersTemporary>> tag retrieved tiddlers as 'temporary'(requires [[TemporaryTiddlersPlugin]])
{{{usage: <<option chkExternalTiddlersTemporary>>}}}
tag retrieved tiddlers with: <<option txtExternalTiddlersTags>>
{{{usage: <<option txtExternalTiddlersTags>>}}}
__password-protected server settings //(optional, if needed)//:__
>username: <<option txtRemoteUsername>> password: <<option txtRemotePassword>>
>{{{usage: <<option txtRemoteUsername>> <<option txtRemotePassword>>}}}
>''note: these settings are also used by [[LoadTiddlersPlugin]] and [[ImportTiddlersPlugin]]''
<<<
!!!!!Revisions
<<<
2011.02.08 1.3.2 fixed parsing of external links to allow retrieval of tiddler sections from remote files. NOTE: //requires SectionLinksPlugin v1.4.1 or above//). Also, calls to saveTiddler() use config.defaultCustomFields for TiddlySpace compatibility.
|please see [[ExternalTiddlersPluginInfo]] for additional revision details|
2007.11.25 1.0.0 initial release - moved from CoreTweaks
<<<
!!!!!Code
***/
//{{{
version.extensions.ExternalTiddlersPlugin= {major: 1, minor: 3, revision: 2, date: new Date(2011,2,8)};
// optional automatic import/create for missing tiddlers
if (config.options.chkExternalTiddlersImport==undefined) config.options.chkExternalTiddlersImport=true;
if (config.options.chkExternalTiddlersTemporary==undefined) config.options.chkExternalTiddlersTemporary=true;
if (config.options.chkExternalTiddlersQuiet==undefined) config.options.chkExternalTiddlersQuiet=false;
if (config.options.txtExternalTiddlersTags==undefined) config.options.txtExternalTiddlersTags="external";
if (config.options.txtRemoteUsername==undefined) config.options.txtRemoteUsername="";
if (config.options.txtRemotePassword==undefined) config.options.txtRemotePassword="";
config.macros.tiddler.externalTiddlers_handler = config.macros.tiddler.handler;
config.macros.tiddler.handler = function(place,macroName,params,wikifier,paramString,tiddler)
{
params = paramString.parseParams("name",null,true,false,true);
var names = params[0]["name"];
var list = names[0];
var items = list.split("|");
var className = names[1] ? names[1] : null;
var args = params[0]["with"];
// UTILITY FUNCTIONS
function extract(text,tids) { // get tiddler source content from plain text or TW doc
if (!text || !tids || !tids.length) return text; // no text or no tiddler list... return text as-is
var remoteStore=new TiddlyWiki();
if (!remoteStore.importTiddlyWiki(text)) return text; // not a TW document... return text as-is
var out=[]; for (var t=0;t<tids.length;t++)
{ var txt=remoteStore.getTiddlerText(tids[t]); if (txt) out.push(txt); }
return out.join("\n");
}
function substitute(text,args) { // replace "substitution markers" ($1-$9) with macro param values (if any)
if (!text || !args || !args.length) return text;
var n=args.length; if (n>9) n=9;
for(var i=0; i<n; i++) { var re=new RegExp("\\$" + (i + 1),"mg"); text=text.replace(re,args[i]); }
return text;
}
function addTiddler(src,text,tids) { // extract tiddler(s) from text and create local copy
if (!config.options.chkExternalTiddlersImport) return; // not enabled... do nothing
if (!text || !tids || !tids.length) return; // no text or no tiddler list... do nothing
var remoteStore=new TiddlyWiki();
if (!remoteStore.importTiddlyWiki(text)) // not a TW document... create a single tiddler from text
makeTiddler(src,text,tids[0]);
else // TW document with "permaview-like" suffix... copy tiddler(s) from remote store
for (var t=0;t<tids.length;t++)
insertTiddler(src,remoteStore.getTiddler(tids[t]));
return;
}
function makeTiddler(src,text,title) { // create a new tiddler object from text
var who=config.options.txtUserName; var when=new Date();
var msg="/%\n\nThis tiddler was automatically created using ExternalTiddlersPlugin\n";
msg+="by %0 on %1\nsource: %2\n\n%/";
var tags=config.options.txtExternalTiddlersTags.readBracketedList();
if (config.options.chkExternalTiddlersTemporary) tags.pushUnique(config.options.txtTemporaryTag);
store.saveTiddler(null,title,msg.format([who,when,src])+text,who,when,tags,config.defaultCustomFields);
if (!config.options.chkExternalTiddlersQuiet) displayMessage("Created new tiddler '"+title+"' from text file "+src);
}
function insertTiddler(src,t) { // import a single tiddler object into the current document store
if (!t) return;
var who=config.options.txtUserName; var when=new Date();
var msg="/%\n\nThis tiddler was automatically imported using ExternalTiddlersPlugin\n";
msg+="by %0 on %1\nsource: %2\n\n%/";
var newtags=new Array().concat(t.tags,config.options.txtExternalTiddlersTags.readBracketedList());
if (config.options.chkExternalTiddlersTemporary) newtags.push(config.options.txtTemporaryTag);
store.saveTiddler(null,t.title,msg.format([who,when,src])+t.text,t.modifier,t.modified,newtags,
merge(t.fields,config.defaultCustomFields,true));
if (!config.options.chkExternalTiddlersQuiet) displayMessage("Imported tiddler '"+t.title+"' from "+src);
}
function getGUID() // create a Globally Unique ID (for async reference to DOM elements)
{ return new Date().getTime()+Math.random().toString(); }
// loop through "|"-separated list of alternative tiddler/file/URL references until successful
var fallback="";
for (var i=0; i<items.length; i++) { var src=items[i];
// if tiddler (or shadow) exists, replace reference list with current source name and apply core handler
if (store.getTiddlerText(src)) {
arguments[2][0]=src; // params[] array
var p=arguments[4].split(list); arguments[4]=p[0]+src+p[1]; // paramString
this.externalTiddlers_handler.apply(this,arguments);
break; // stop processing alternatives
}
// tiddler doesn't exist, and not an external file/URL reference... skip it
if (!config.formatterHelpers.isExternalLink(src)) {
if (!fallback.length) fallback=src; // title to use when importing external tiddler
continue;
}
// separate 'permaview' list of tiddlers (if any) from file/URL (i.e., '#name name name..." suffix)
var p=src.split("#"); src=p.shift(); var tids=p.join('#').readBracketedList(false);
// if reference is to a remotely hosted document or the current document is remotely hosted...
if (src.substr(0,4)=="http" || document.location.protocol.substr(0,4)=="http") {
if (src.substr(0,4)!="http") // fixup URL for relative remote references
{ var h=document.location.href; src=h.substr(0,h.lastIndexOf("/")+1)+src; }
var wrapper = createTiddlyElement(place,"span",getGUID(),className); // create placeholder for async rendering
var callback=function(success,params,text,src,xhr) { // ASYNC CALLBACK
if (!success) { displayMessage(xhr.status); return; } // couldn't read remote file... report the error
if (params.fallback.length)
addTiddler(params.url,text,params.tids.length?params.tids:[params.fallback]); // import tiddler
var wrapper=document.getElementById(params.id); if (!wrapper) return;
wikify(substitute(extract(text,params.tids),params.args),wrapper); // ASYNC RENDER
};
var callbackparams={ url:src, id:wrapper.id, args:args, tids:tids, fallback:fallback } // ASYNC PARAMS
var name=config.options.txtRemoteUsername; // optional value
var pass=config.options.txtRemotePassword; // optional value
var x=doHttp("GET",src,null,null,name,pass,callback,callbackparams,null)
if (typeof(x)=="string") // couldn't start XMLHttpRequest... report error
{ displayMessage("error: cannot access "+src); displayMessage(x); }
break; // can't tell if async read will succeed.... stop processing alternatives anyway.
}
else { // read file from local filesystem
var text=loadFile(getLocalPath(src));
if (!text) { // couldn't load file... fixup path for relative reference and retry...
var h=document.location.href;
var text=loadFile(getLocalPath(decodeURIComponent(h.substr(0,h.lastIndexOf("/")+1)))+src);
}
if (text) { // test it again... if file was loaded OK, render it in a class wrapper
if (fallback.length) // create new tiddler using primary source name (if any)
addTiddler(src,text,tids.length?tids:[fallback]);
var wrapper=createTiddlyElement(place,"span",null,className);
wikify(substitute(extract(text,tids),args),wrapper); // render
break; // stop processing alternatives
}
}
}
};
//}}}
|Name|ExternalTiddlersPluginInfo|
|Source|http://www.TiddlyTools.com/#ExternalTiddlersPlugin|
|Documentation|http://www.TiddlyTools.com/#ExternalTiddlersPluginInfo|
|Version|1.3.2|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|documentation for ExternalTiddlersPlugin|
This plugin extends the {{{<<tiddler>>}}} macro syntax so you can retrieve and wikify content directly from external files or remote URLs. You can also define alternative "fallback" sources to provide basic "import on demand" handling by automatically creating/importing tiddler content from external sources when the specified ~TiddlerName does not already exist in your document.
!!!!!Configuration
>see ExternalTiddlersPlugin
!!!!!Usage
<<<
The standard TiddlyWiki core syntax for the {{{<<tiddler>>}}} macro is:
>{{{<<tiddler TiddlerName with: param param param ...>>}}}
where the optional {{{with: param param param...}}} values are used to replace any corresponding "substitution markers" ($1 to $9) that may be embedded in the referenced tiddler content.
This plugin allows the {{{<<tiddler>>}}} macro to ''use external file/URL references in place of the usual ~TiddlerName parameter'', so that you can render wiki-formatted source content retrieved from an external file/URL reference (as determined by the core's isExternalLink() test function), ''//as if// it had come from a tiddler in the current document''. The external file/URL can be either ''a relative or absolute reference'' and can contain ''"plain text" or a full TiddlyWiki document''. When using a TiddlyWiki document, you must specify which tiddlers should be included in the output by appending a permaview-like suffix to the file or URL reference, e.g.:
>{{{<<tiddler "myfile.txt" with: param param param...>>}}}
>or
>{{{<<tiddler "myfile.html#TiddlerName TiddlerName..." with: param param param...>>}}}
>or
>{{{<<tiddler "http://www.TiddlyWiki.com/index.html#HelloThere" with: param param param...>>}}}
If the plugin-enhanced {{{<<tiddler>>}}} macro is unable to retrieve the external content -- perhaps because the file doesn't exist or doesn't contain the requested tiddler(s), or cross-domain security blocked file access, or the network/server "timed out", etc., -- then it produces no output (i.e., just as when the standard {{{<<tiddler>>}}} macro is given a ~TiddlerName does not exist in the current document.)
<<<
!!!!!Using alternative "fallback" references
<<<
In addition to using external file/URL references in place of the usual ~TiddlerName, the plugin also allows you to use a ''fallback list'' consisting of a combination of alternative sources: tiddlers, local files, and/or URL references, each separated by "|". The first reference in a fallback list is the "primary source"; the remaining references are "fallback sources". The plugin will attempt to retrieve content from each fallback source until one is successfully retrieved or all alternatives have been tried.
For example, if you create a tiddler called [[HelloThere]], as well as a remotely-hosted TW document containing a published tiddler, also called [[HelloThere]], then you can write:
>{{{<<tiddler [[HelloThere|http://www.TiddlyWiki.com/#HelloThere]]>>}}}
When [[HelloThere]] is present in the local document, it is processed in the normal manner. However, if you delete the local [[HelloThere]] tiddler, the plugin will attempt to retrieve the [[HelloThere]] tiddler from the indicated remote URL.
Please note: although you can list any number of alternative sources, in whatever order you prefer, retrieval from a remote URL occurs asynchronously via XMLHttpRequest() processing. As a consequence, there can be ''no more than one remote URL reference in the fallback list'', and any alternatives that follow a remote URL reference will not be processed.
<<<
!!!!!Automatically import/create missing tiddlers
<<<
When content is retrieved from an external fallback source, the plugin can automatically import/create tiddler(s) containing that content into your document, allowing you to display, modify, save and/or search for text in that tiddler from within your own document, without needing to retrieve it again from the external source.
If no local ~TiddlerName(s) are specified in the fallback list (i.e., only direct file/URL references are present), then a tiddler will NOT be created, so that each time you render the tiddler display the external source will be re-read in order to render the most recently saved external file content. To illustrate using the example from above:
> {{{<<tiddler [[HelloThere|http://www.TiddlyWiki.com/#HelloThere]]>>}}}
will automatically create a locally-stored [[HelloThere]] tiddler, so that the external source is only accessed the first time the content is rendered, while:
> {{{<<tiddler [[http://www.TiddlyWiki.com/#HelloThere]]>>}}}
will re-load the content from the external source each time the display is rendered.
For easy identification, any tiddlers that are automatically created/imported are tagged with <<tag external>> (or other custom-defined tag values). These tiddlers can also be automatically tagged with <<tag temporary>> for use with [[TemporaryTiddlersPlugin]], which will skip over those tiddlers when saving changes to your document so that when you reload the document, the temporary tiddlers will no longer be present and will be retrieved anew from the external source, on demand, when (or if) they are needed. Important reminder: ''If you modify a temporary tiddler and want to retain it in your local document, be sure to remove the <<tag temporary>> tag from the tiddler before saving.''
<<<
!!!!!~XMLHttpRequest: performance and security issues
<<<
This plugin uses asynchronous XMLHttpRequest() processing to access external content directly from URLs hosted on remote web servers. However, ''cross-domain access from one remote domain to another using XMLHttpRequest() processing is generally restricted for security reasons''. As a result, URL references between server-hosted documents will not work unless those documents are located within the same domain. In order to ensure that external content included in server-hosted documents will be displayed as intended, you should ''always use either a relative path/file reference or an http: reference located on the same domain as the published document.'' for any document you intend to publish.
Note: Some hosting providers, such as http://www.TiddlySpot.com/ offer ''"proxy" services that may allow you to bypass the security restrictions'' for certain designated remote web sites. Consult your hosting service for information regarding their proxy arrangments (if any).
<<<
!!!!!Revisions
<<<
2011.02.08 1.3.2 fixed parsing of external links to allow retrieval of tiddler sections from remote files. NOTE: //requires SectionLinksPlugin v1.4.1 or above//). Also, calls to saveTiddler() use config.defaultCustomFields for TiddlySpace compatibility.
2008.10.27 1.3.1 in insertTiddler(), fixed Safari bug by replacing static Array.concat(...) with new Array().concat(...)
2008.01.08 [*.*.*] plugin size reduction: documentation moved to ExternalTiddlersPluginInfo
2008.01.03 1.3.0 use lower-level doHttp() instead loadRemoteFile() so that optional username/password values can be used in XMLHttpRequest
2007.12.22 1.2.2 in handler(), when reading from local file with relative path fixup, use decodeURIComponent() instead of decodeURI
2007.11.30 1.2.1 lots of code/documentation cleanup. renamed option cookies. changed auto tag value to "external".
2007.11.27 1.2.0 added support for automatically importing external tiddlers
2007.11.26 1.1.1 improved XMLHttpRequest() error reporting for cross-domain security issues
2007.11.26 1.1.0 added support for multiple alternative fallback references
2007.11.25 1.0.0 initial release - moved from CoreTweaks
<<<
List of figures:
<<tagging>>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f001.jpg" class="SCImage"><div> Ventilation (V)-perfusion (Q) defects. <b>A,</b> Schematic showing normal ventilation and perfusion; <b>B,</b> schematic showing ventilation defect; <b>C,</b> schematic of perfusion defect. See text for discussion. P<span class="overbar">v</span>CO<sub>2</sub>, partial pressure of carbon dioxide in mixed venous blood; P<span class="overbar">v</span>O<sub>2</sub>, partial pressure of oxygen in mixed venous blood. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. Philadelphia, Mosby Elsevier, 2008, p 76, Fig. 3-5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f010.jpg" class="SCImage"><div> <b>A</b>, Atrophy of the brain. Note the narrow gyri and widened sulci. The meninges have been stripped from the right half of the brain. <b>B,</b> Pancreas in a patient with cystic fibrosis showing dilated ducts filled with thickened eosinophilic material. The ducts are surrounded with fibrous tissue. <b>C,</b> Left ventricular hypertrophy, showing the thickened free left ventricular wall (right side) and the thickened interventricular septum. The right ventricle wall (left side) is of normal thickness. <b>D,</b> Benign prostatic hyperplasia. The prostatic glands show infolding into the glandular spaces. <b>E,</b> Barrett's esophagus showing an extensive area of glandular metaplasia with numerous goblet cells. A small section of squamous epithelium remains on the right. <b>F,</b> Section of bronchus from a smoker showing focal squamous metaplasia (<i>long arrow</i>). Normal ciliated, pseudostratified columnar epithelium is present on the right (<i>short arrow</i>). <b>G,</b> Squamous dysplasia of the cervix, a precursor of squamous cell carcinoma. There is a lack of orientation of the squamous cells throughout the upper two thirds of the epithelium. Many of the nuclei are enlarged (<i>arrows</i>), are hyperchromatic, and have irregular nuclear margins. <i>(<b>A</b> from Kumar V, Abbas A, Fausto N, Mitchell, R: Robbins Basic Pathology, 8th ed. Philadelphia, WB Saunders, 2007, p 5, Fig. 1-4; <b>B, D,</b> and <b>E</b> from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, pp 169, 249, 111, Figs. 9-6, 12-32, 6-26, respectively; <b>C</b> and <b>G</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, pp 561, 1075, Figs. 12-3A; 22-19C, respectively; <b>F</b> from Corrin B: Pathology of the Lungs. London, Churchill Livingstone, 2000, p 460, Fig. 13.1.1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f011.jpg" class="SCImage"><div> <b>A,</b> Acute myocardial infarction (MI) showing coagulation necrosis. This section of myocardial tissue is from a 3-day-old acute MI. The outlines of the myocardial fibers are intact; however, they lack nuclei and cross-striations. A neutrophilic infiltrate is present between some of the dead fibers. <b>B,</b> Acute MI showing a pale infarction of the posterior wall of the left ventricle (bottom left). <b>C,</b> Hemorrhagic infarction of lung. There is a roughly wedge-shaped area of hemorrhage extending to the pleural surface. The arrow shows an embolus in one of the pulmonary artery tributaries. <b>D,</b> Dry gangrene involves the first four toes. The dark black areas of gangrene are bordered by light-colored, parchment-like skin. <b>E,</b> Cerebral infarction showing liquefactive necrosis of the cerebral cortex leaving a large cystic cavity. <b>F,</b> Wet gangrene of the leg. Note the pus at the closing edges of the below-the-knee amputation site. <b>G,</b> Caseous granuloma showing a central area of acellular, necrotic material (<i>asterisk</i>) surrounded by activated macrophages (epithelioid cells), lymphocytes, and multiple multinucleated Langhans-type giant cells. <b>H,</b> Enzymatic fat necrosis in acute pancreatitis. Dark areas of hemorrhage are present in the head of the pancreas (left side), and focal areas of pale fat necrosis (<i>arrow</i>) are present in the peripancreatic fat. <i>(<b>A</b> from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, 375, Fig. 17-15; <b>B</b> from Damjanov I, Linder J: Anderson's Pathology, 10th ed. St. Louis, Mosby, 1996, p 374, Fig. 17-13; <b>C, E, G,</b> and <b>H</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, pp 138, 1365, 83, 943, Figs. 4-19A, 28-16, 2-33, 19-5, respectively; <b>D</b> from Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 18, Fig. 1-24; <</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f012.jpg" class="SCImage"><div> Apoptosis in viral hepatitis. The arrow shows a shrunken eosinophilic staining cell with pyknotic nucleus within a clear space. <i>(From Damjanov I: Pathophysiology. Philadelphia, Saunders Elsevier, 2009, p 301, Fig. 8.22.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f002.jpg" class="SCImage"><div> Oxygen-binding curve (OBC). Note that at the Po<sub>2</sub> in the tissue (ranges from 20 to 50 mm Hg) a left-shifted OBC still has an O<sub>2</sub> saturation (Sao<sub>2</sub>) of 80% (only released 20% of its O<sub>2</sub> to tissue), a normal-shifted OBC has an Sao<sub>2</sub> of 50% (only released 50% of its O<sub>2</sub> to tissue), and a right-shifted curve has an Sao<sub>2</sub> of 20% (released 80% of its O<sub>2</sub> to tissue). 2,3-Bisphosphoglycerate (BPG) improves O<sub>2</sub> delivery to tissue by stabilizing the hemoglobin (Hb) in the taut form, which decreases O<sub>2</sub> affinity, hence facilitating the movement of O<sub>2</sub> from Hb into tissue by diffusion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f003.jpg" class="SCImage"><div> Oxidative phosphorylation. See text for discussion. <i>(From Pelley J, Goljan E: Rapid Review Biochemistry, 2nd ed. St. Louis, Mosby, 2007, p 81, Fig. 5-8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f004.jpg" class="SCImage"><div> Watershed infarction showing a wedge-shaped hemorrhagic infarction at the junction of the anterior and middle cerebral arteries. <i>(From Damjanov I, Linder J: Anderson's Pathology, 10th ed. St. Louis, Mosby, 1996, p 375, Fig. 17-16.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f005.jpg" class="SCImage"><div> Hyperplasia of smooth endoplasmic reticulum (<i>2</i>) and damaged mitochondria (megamitochondria, <i>1</i>) in alcoholic liver disease. <i>(From MacSween R, Burt A, Portmann B, et al: Pathology of the Liver, 4th ed. London, Churchill Livingstone, 2002, p 288, Fig. 6-20.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f006.jpg" class="SCImage"><div> Chédiak-Higashi neutrophil (<i>arrow</i>) and lymphocytes with giant granules. See text for discussion. <i>(From McPherson R, Pincus M: Henry's Clinical Diagnosis and Management by Laboratory Methods, 21st ed. Philadelphia, WB Saunders, 2007, p 551, Fig. 32-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f007.jpg" class="SCImage"><div> Mallory bodies. Hyaline (eosinophilic) inclusions (<i>arrow</i>) are present in the cytosol of hepatocytes. Many of the hepatocytes have vacuoles containing triglyceride. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 34, Fig. 1-34A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f008.jpg" class="SCImage"><div> Fatty change of the liver. Vacuoles containing triglyceride are noted in most of the hepatocytes. The nucleus is displaced to the periphery. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 36, Fig. 1-36B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-001-f009.jpg" class="SCImage"><div> Radiograph showing multiple dystrophic calcifications in the pancreas in a patient with chronic pancreatitis. <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 155, Fig. 4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f001.jpg" class="SCImage"><div> Left ventricular hypertrophy. The heart in the middle has a normal thickness of the left ventricle (LV). The heart on the left (<b>A</b>) has concentric hypertrophy of the LV, while the heart on the right (<b>B</b>) has eccentric hypertrophy of the LV. <i>(Reproduced with permission from Edwards WD: Cardiac anatomy and examination of cardiac specimens. In Emmanouilides GC, Riemenschneider TA, Allen HD, Gutgesell HP [eds]: Moss and Adams Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adults, 5th ed. Philadelphia, Williams & Wilkins, 1995, p 86.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f010.jpg" class="SCImage"><div> Fetal circulation. See text for discussion. <i>(From Moore NA, Roy WA: Rapid Review Gross and Developmental Anatomy, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 56, Fig. 2-23.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f011.jpg" class="SCImage"><div> Cyanotic congenital heart disease. This patient with a ventricular septal defect that eventually showed reversed shunting (Eisenmenger syndrome) has cyanosis and clubbing of the nails. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 93, Fig. 14-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f012.jpg" class="SCImage"><div> <b>A,</b> Ventricular septal defect (VSD). Refer to the text for discussion. <b>B,</b> Atrial septal defect (ASD). See text for discussion. <b>C,</b> Patent ductus arteriosus (PDA). See text for discussion. <b>D,</b> Tetralogy of Fallot. Refer to the text for discussion. <b>E,</b> Complete transposition of the great vessels. See text for discussion. <b>F,</b> Postductal coarctation. See text for discussion. Ao, aorta; AV, aortic valve; DA, ductus arteriosus; IVC, inferior vena cava; LA, left atrium; LV, left ventricle; LVH, left ventricular hypertrophy; MV, mitral valve; PA, pulmonary artery; PH, pulmonary hypertension; PV, pulmonary valve; RA, right atrium; RV, right ventricle; RVH, right ventricular hypertrophy; SVC, superior vena cava; TV, tricuspid valve. <i>(<b>B, C, E,</b> and <b>F</b> from Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998</i>.)</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f013.jpg" class="SCImage"><div> Acute rheumatic fever. Uniform, verrucoid-appearing sterile vegetations appear along the line of closure of the mitral valve. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 13, Fig. 1-22.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f014.jpg" class="SCImage"><div> Mitral stenosis. Refer to the text for discussion. Ao, aorta; AV, aortic valve; IVC, inferior vena cava; LA, left atrium; LV, left ventricle; LVH, left ventricular hypertrophy; MV, mitral valve; PA, pulmonary artery; PH, pulmonary hypertension; PV, pulmonary valve; RA, right atrium; RV, right ventricle; RVH, right ventricular hypertrophy; SVC, superior vena cava; TV, tricuspid valve.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f015.jpg" class="SCImage"><div> Mitral regurgitation. See text for discussion. Ao, aorta; AV, aortic valve; IVC, inferior vena cava; LA, left atrium; LV, left ventricle; LVH, left ventricular hypertrophy; MV, mitral valve; PA, pulmonary artery; PH, pulmonary hypertension; PV, pulmonary valve; RA, right atrium; RV, right ventricle; SVC, superior vena cava; TV, tricuspid valve. <i>(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f016.jpg" class="SCImage"><div> Mitral valve prolapse. The <i>arrow</i> shows prolapse of the posterior mitral leaflet into the left atrium. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 592, Fig. 12-23.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f017.jpg" class="SCImage"><div> Aortic stenosis. The superior view shows a bicuspid aortic valve with severe stenosis due to fibrocalcific involvement of the two valve cusps. <i>(From Silver MD, Gotlieb AI, Schoen FJ: Cardiovascular Pathology, 3rd ed. London, Churchill Livingstone, 2001, p 424, Fig. 13.26B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f018.jpg" class="SCImage"><div> Aortic stenosis. See text for discussion. Ao, aorta; AV, aortic valve; IVC, inferior vena cava; LA, left atrium; LV, left ventricle; LVH, left ventricular hypertrophy; MV, mitral valve; PA, pulmonary artery; PH, pulmonary hypertension; PMI, point of maximal impulse; PV, pulmonary valve; RA, right atrium; RV, right ventricle; SVC, superior vena cava; TV, tricuspid valve. <i>(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f019.jpg" class="SCImage"><div> Aortic regurgitation. See text for discussion. Ao, aorta; AV, aortic valve; IVC, inferior vena cava; LA, left atrium; LV, left ventricle; LVH, left ventricular hypertrophy; MV, mitral valve; PA, pulmonary artery; PV, pulmonary valve; RA, right atrium; RV, right ventricle; SVC, superior vena cava; TV, tricuspid valve. <i>(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f002.jpg" class="SCImage"><div> Chest frontal radiograph showing pulmonary edema. Note the fluffy alveolar infiltrates throughout both lung fields. <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 596, Fig. 84-2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f020.jpg" class="SCImage"><div> Acute bacterial endocarditis. Large, friable, and irregular vegetation (<i>arrow</i>) is present on the margin of the mitral valve. Smaller vegetations are present along the line of closure of the valve. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 11, Fig. 1-16.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f021.jpg" class="SCImage"><div> Splinter hemorrhages in the nail bed. Note the longitudinal red hemorrhages in the nail bed. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 147, Fig. 8-10.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f022.jpg" class="SCImage"><div> Myocarditis. The biopsy shows a lymphocytic infiltrate with dissolution of myocardial fibers. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 15, Fig. 1-28.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f023.jpg" class="SCImage"><div> Hemopericardium. Note the "water bottle" configuration of the blood in the pericardial cavity. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 52, Fig. 2-82.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f024.jpg" class="SCImage"><div> Posteroanterior chest radiograph showing a pericardial effusion. Note the loss of the usual heart borders and the "water bottle" configuration similar to that seen in the hemopericardium in <xref xref="F010023" type="FIGURE">Fig. 10-23</xref>. <i>(Courtesy of Sven Paulin, MD.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f025.jpg" class="SCImage"><div> Dilated cardiomyopathy. Note the global enlargement of the heart and the dilated ventricle on the right and atrium on the left. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 17, Fig. 1-35.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f026.jpg" class="SCImage"><div> Schematic of hypertrophic cardiomyopathy. Refer to the text for discussion. Ao, aorta; AV, aortic valve; IVC, inferior vena cava; IVS, interventricular septum; LA, left atrium; LV, left ventricle; LVH, left ventricular hypertrophy; MV, mitral valve; PA, pulmonary artery; PV, pulmonary valve; RA, right atrium; RV, right ventricle; SVC, superior vena cava; TV, tricuspid valve.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f027.jpg" class="SCImage"><div> Hypertrophic cardiomyopathy. The heart (<b>A</b>) shows asymmetric hypertrophy of the interventricular septum (<i>black arrow</i>) with marked narrowing of the outflow tract. The histologic section of the conduction system in the septum (<b>B</b>) shows aberrant myofibers. <i>(<b>A</b> from Schoen FJ: Interventional and Surgical Cardiovascular Pathology: Clinical Correlations and Basic Principles. Philadelphia, Saunders, 1989; <b>B</b> from Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 413, Fig. 11-25.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f028.jpg" class="SCImage"><div> Cardiac myxoma in the left atrium. Note the large red mass in the left atrium. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 27, Fig. 1-65A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f003.jpg" class="SCImage"><div> Distention of internal jugular vein: The patient has right-sided heart failure. <i>(From <a href="http://courses.cvcc.vccs.edu/WisemanDljugular_vein_distention.htm" target="_blank">http://courses.cvcc.vccs.edu/WisemanDljugular_vein_distention.htm</a>.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f004.jpg" class="SCImage"><div> Electrocardiogram with ST segment depression. Tracing A is the patient at rest with 1 representing the PQ junction (baseline reference); 2, the J point, where the QRS complex joins the ST segment; and 3, the ST segment 80 msec from the PQ point. Tracing B shows the amount of ST segment depression measured 80 msec past the J point is 4 mm. <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 481, Fig. 70-2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f005.jpg" class="SCImage"><div> Acute myocardial infarction (day 7) in the posterior wall of the left ventricle. The yellow area (<i>arrow</i>) is surrounded by a rim of dark, red granulation tissue. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 22, Fig. 1-47.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f006.jpg" class="SCImage"><div> Acute myocardial infarction with rupture of the free wall of the left ventricle (<i>arrow</i>). This rupture is unusual in that it occurred 3 weeks after an acute myocardial infarction. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 35, Fig. 2-30.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f007.jpg" class="SCImage"><div> Left ventricular aneurysm. The bulging aneurysm has a thin wall of scar tissue. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 24, Fig. 1-58.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f008.jpg" class="SCImage"><div> Cardiac enzymes used in the diagnosis of an acute myocardial infarction. CK-MB, creatine kinase MB; LDH, lactate dehydrogenase. See text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-010-f009.jpg" class="SCImage"><div> Electrocardiogram showing an acute anterior myocardial infarction. There is ST segment elevation in lead 1 (<i>solid arrow</i>), aVL, and V<sub>1</sub> to V<sub>6</sub> and Q waves (<i>interrupted arrow</i>) in leads V<sub>1</sub> to V<sub>4</sub>. <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 502, Fig. 72-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f001.jpg" class="SCImage"><div> Peripheral blood reticulocytes with supravital stain (new methylene blue). Red blood cells with thread-like material in the cytosol represent residual RNA filaments and protein (<i>arrow</i>). <i>(From Hoffbrand AV: Color Atlas: Clinical Hematology, 3rd ed. St. Louis, Mosby, 2000, Fig. 1-43B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f010.jpg" class="SCImage"><div> Koilonychia. Note the spoon shape of the nail bed. <i>(From Savin JAA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, p 118, Fig. 4.60.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f011.jpg" class="SCImage"><div> Peripheral blood smear in iron deficiency anemia. The enlarged central area of pallor in the red blood cell (<i>arrows</i>) indicates a decrease in hemoglobin synthesis, which is characteristic of the microcytic anemias. The mean corpuscular hemoglobin concentration is decreased. <i>(From Wickramasinghe SE, McCullough J: Blood and Bone Marrow Pathology. Philadelphia, Churchill Livingstone, 2003, Fig. 11-6.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f012.jpg" class="SCImage"><div> Gene deletions in α-thalassemia in the black population (<b>A</b>) and Asian population (<b>B</b>). Four α-genes are involved in α-globin chain synthesis. The black population type is associated with a loss of one gene on each chromosome (<i>trans</i> configuration: α/-α/-; schematic A). In the Asian type, there is a loss of both genes on the same chromosome (<i>cis</i> configuration: -/-α/α, B). <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 158, Fig. 5-11.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f013.jpg" class="SCImage"><div> Ringed sideroblasts in a bone marrow aspirate. Dark blue iron granules around the nucleus of developing normoblasts (<i>arrows</i>) represent iron trapped within mitochondria and indicate a defect in mitochondrial heme synthesis. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 431, Fig. 10-27.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f014.jpg" class="SCImage"><div> Peripheral blood with coarse basophilic stippling of red blood cells in lead poisoning. Note the mature red blood cell containing numerous dots representing ribosomes (<i>arrow</i>). Lead denatures ribonuclease; hence, the ribosomes persist in the cytoplasm. <i>(From Naeim F: Atlas of Bone Marrow and Blood Pathology. Philadelphia, WB Saunders, 2001, p 27, Fig. 2-22M.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f015.jpg" class="SCImage"><div> Abdominal radiograph showing numerous metallic foci representing lead chips. <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 310, Fig. 6.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f016.jpg" class="SCImage"><div> Bone radiograph showing densities (lead deposits; <i>arrows</i>) in the epiphysis of the distal femur and proximal tibia. <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 310, Fig. 5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f017.jpg" class="SCImage"><div> Megaloblasts in a bone marrow aspirate. Note the open chromatin pattern and enlarged nuclei of red blood cell and white blood cell precursors indicating a lack of nuclear maturation. <i>(From Goldman L, Ausiello, D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 1239, Fig. 170-4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f018.jpg" class="SCImage"><div> Vitamin B<sub>12</sub> and folate in DNA metabolism. See text for discussion. dTMP, deoxythymidine monophosphate; dUMP, deoxyuridine monophosphate; FH<sub>2</sub>, dihydrofolate; FH<sub>4</sub>, tetrahydrofolate; FU, fluorouracil; MTX, methotrexate; TMP, trimethoprim. <i>(From Pelley J, Goljan EF: Rapid Review: Biochemistry. St. Louis, Mosby, 2004, Fig. 4-3.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f019.jpg" class="SCImage"><div> Odd-chain fatty acid metabolism. See text for discussion. <i>(From Pelley J, Goljan E: Rapid Review Biochemistry, 2nd ed. Philadelphia, Mosby, 2007, p 117, Fig. 7-4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f002.jpg" class="SCImage"><div> Correction of the reticulocyte count for degree of anemia. Note that the normal reticulocyte count is 3% when 3 reticulocytes (pale blue RBCs) are expressed as a percentage of 100 RBCs (red blood cells) in the microscopic field. However, the same 3 reticulocytes account for 10% of the RBCs in the patient with anemia, who has only 30 RBCs in the microscopic field. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 146, Fig. 5-3.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f020.jpg" class="SCImage"><div> Subacute combined degeneration of the thoracic cervical cord. Note the pale areas of demyelination in the posterior columns and the lateral corticospinal tracts. <i>(From Wickramasinghe SN, McCullough J: Blood and Bone Marrow Pathology. London, Churchill Livingstone, 2003, p 237, Fig. 12-10B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f021.jpg" class="SCImage"><div> Peripheral blood in megaloblastic anemia showing a hypersegmented neutrophil (<i>solid arrow</i>) with nine lobes. Neutrophils normally have less than five nuclear segments. Hypersegmented neutrophils are excellent markers of folate and vitamin B<sub>12</sub> deficiency. The enlarged, egg-shaped red blood cells (macro-ovalocytes; <i>interrupted arrow</i>) characteristic of macrocytic anemias are associated with problems in DNA maturation. <i>(From Naeim F: Atlas of Bone Marrow and Blood Pathology. Philadelphia, WB Saunders, 2001, p 180, Fig. 14-10B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f022.jpg" class="SCImage"><div> Round macrocytes and target cells in chronic alcoholism. Note the round macrocytes with target cell formation (<i>arrows</i>). <i>(From Wickramasinghe SN, McCullough J: Blood and Bone Marrow Pathology. London, Churchill Livingstone, 2003, Fig. 6-2F.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f023.jpg" class="SCImage"><div> Bone marrow biopsy in aplastic anemia. The biopsy shows a marrow largely replaced by adipose cells. Scattered lymphocytes are present in between adipose cells. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, Fig. 13-27B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f024.jpg" class="SCImage"><div> Extravascular (<b>A</b>) and intravascular (<b>B</b>) hemolysis of red blood cells. See text for discussion. <i>(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998, Fig. 12-2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f025.jpg" class="SCImage"><div> Peripheral blood with spherocytes in hereditary spherocytosis. Numerous, round, dense red blood cells without central areas of pallor represent spherocytes (<i>arrows</i>). The mean corpuscular hemoglobin concentration is increased. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 75, Fig. 5-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f026.jpg" class="SCImage"><div> Peripheral blood with elliptocytes. In hereditary elliptocytosis, elliptocytes constitute more than 25% of the red blood cells, as in this smear. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, Fig. 5-8A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f027.jpg" class="SCImage"><div> Peripheral blood with sickle cells (<i>interrupted arrows</i>) and target cells, showing the dense, boat-shaped sickle cells. Cells with a bull's-eye appearance are target cells (<i>solid arrows</i>), which have excess RBC membrane that bulges in the center of the cell. <i>(From Hoffbrand AV: Color Atlas: Clinical Hematology, 3rd ed. St. Louis, Mosby, 2000, p 103, Fig. 5-85A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f028.jpg" class="SCImage"><div> Peripheral blood with sickle cells and Howell-Jolly bodies. The three dense boat-shaped sickle cells and the two cells containing a single dark, round inclusion (<i>arrows</i>) represent nuclear remnants. Howell-Jolly bodies in sickle cell disease indicate splenic dysfunction. <i>(From Henry JB: Clinical Diagnosis and Management by Laboratory Methods, 20th ed. Philadelphia, WB Saunders, 2001, Fig. 26-2A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f029.jpg" class="SCImage"><div> Pentose phosphate pathway. The enzyme glucose-6-phosphate dehydrogenase catalyzes the irreversible reaction that converts glucose-6-phosphate to 6-phosphogluconate. NADPH (reduced form of nicotinamide adenine dinucleotide phosphate [NADP]) is produced in this reaction and reduces oxidized glutathione (GSSG) to glutathione (GSH), which neutralizes peroxide and converts it to water. <i>(From Goljan EF: Pathology: Saunders Text and Review Series. Philadelphia, WB Saunders, 1998, Fig. 12-10.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f003.jpg" class="SCImage"><div> Polychromasia. The <i>arrow</i> depicts a blue discolored red blood cell without a central area of pallor. <i>(From Naeim F: Atlas of Bone Marrow and Blood Pathology. Philadelphia, WB Saunders, 2001, Fig. 1-15A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f030.jpg" class="SCImage"><div> Peripheral blood smear with a bite cell and inset showing Heinz bodies in glucose-6-phosphate dehydrogenase deficiency. The <i>arrow</i> shows a bite cell with part of the red blood cell membrane removed. The <i>inset</i> shows a peripheral blood smear with a supravital stain visualizing punctate inclusions representing denatured hemoglobin (Heinz bodies). <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, Fig. 13-8; inset from Wickramasinghe SN, McCullough J: Blood and Bone Marrow Pathology. London, Churchill Livingstone, 2003, Fig. 8-8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f031.jpg" class="SCImage"><div> Schematic of pyruvate kinase reaction. See text for discussion. BPG, bisphosphoglycerate. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 183, Fig. 5-26.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f032.jpg" class="SCImage"><div> Peripheral blood smear in pyruvate kinase deficiency. The <i>arrow</i> shows one of many red blood cells with thorny projections (echinocytes) extending from the red blood cell membrane. <i>(From Wickramasinghe SN, McCullough J: Blood and Bone Marrow Pathology. London, Churchill Livingstone, 2003, Fig. 8-10.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f033.jpg" class="SCImage"><div> Schematic of the direct Coombs' test (<b>A</b>) and indirect Coombs' test (<b>B</b>). <b>A,</b> In the direct Coombs' test, red blood cells (RBCs) sensitized with IgG antibodies (or C3b) are agglutinated when Coombs' reagent (rabbit anti-IgG antibody) is added to the test tube. <b>B,</b> In the indirect Coombs' test, IgG antibodies (e.g., anti-D) in the serum must first bind to blood group type O test RBCs added to the test tube. Addition of Coombs' reagent causes the sensitized type O test RBCs to agglutinate, indicating that IgG antibodies are present in the serum. The specificity of the antibodies (e.g., anti-D IgG antibodies) is determined by other tests performed in the blood bank. <i>(From Goljan EF: Pathology: Saunders Text and Review Series. Philadelphia, WB Saunders, 1998, p 289, Fig. 12-11.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f034.jpg" class="SCImage"><div> Red blood cell agglutination in a patient with a cold (IgM) immune hemolytic anemia. <i>(Courtesy of Jean Schafer.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f035.jpg" class="SCImage"><div> Fragmented red blood cells, or schistocytes (<i>arrows</i>), in the peripheral blood. Note their helmet shapes. <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 1174, Fig. 161-10.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f036.jpg" class="SCImage"><div> <i>Plasmodium falciparum</i> ring forms in RBCs. This RBC has two ring forms. Multiple infestation of an RBC is characteristic of <i>P. falciparum</i> malaria. <i>(From Hoffbrand AV: Color Atlas: Clinical Hematology, 3rd ed. St. Louis, Mosby, 2000, p 315, Fig. 18-4C.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f004.jpg" class="SCImage"><div> Skull radiograph showing "hair-on-end" due to expansion of the bone marrow cavity from accelerated erythropoiesis (e.g., severe hemolysis in sickle cell disease). <i>(From Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 49, Fig. 97.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f005.jpg" class="SCImage"><div> Classification of anemia using mean corpuscular volume (MCV). An intrinsic RBC defect indicates a structural or biochemical flaw in the RBCs. An extrinsic RBC defect indicates that the RBCs are structurally normal, but that other factors cause the anemia. G6PD, glucose-6-phosphate dehydrogenase.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f006.jpg" class="SCImage"><div> Normal peripheral blood smear showing RBCs. The RBCs are uniform in size, and the central areas of pallor are slightly less than half the total diameter of an RBC. The four dark objects (<i>arrows</i>) outside the RBCs are platelets. <i>(From Hoffbrand AV: Color Atlas: Clinical Hematology, 3rd ed. St. Louis, Mosby, 2000, p 22, Fig. 1-62.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f007.jpg" class="SCImage"><div> Iron studies in normal people (<b>A</b>) and those with iron deficiency (<b>B</b>), anemia of chronic disease (<b>C</b>), and iron-overload diseases (<b>D</b>). See text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f008.jpg" class="SCImage"><div> Hemoglobin electrophoresis in various hemoglobinopathies. See text for discussion. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 159, Fig. 5-12.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-011-f009.jpg" class="SCImage"><div> Pathophysiology of microcytic anemias. See text for discussion. ALA, aminolevulinic acid.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-012-f001.jpg" class="SCImage"><div> Leukoerythroblastic reaction. The <i>solid arrow</i> shows a tear drop RBC. Immature myeloid cells are also present in a nucleated RBC (<i>interrupted arrow</i>). <i>(From Naeim F: Atlas of Bone Marrow and Blood Pathology. Philadelphia, WB Saunders, 2001, Fig. 4-10B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-012-f010.jpg" class="SCImage"><div> Peripheral blood in hairy cell leukemia. Clusters of neoplastic cells show dense chromatin and cytoplasmic projections. <i>(From Naeim F: Atlas of Bone Marrow and Blood Pathology. Philadelphia, WB Saunders, 2001, Fig. 8-20A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-012-f002.jpg" class="SCImage"><div> Normal morphology of eosinophil (<b>A</b>), basophil (<b>B</b>), lymphocyte (<b>C</b>), and monocyte (<b>D</b>). The cytoplasm of an eosinophil (<b>A</b>) is packed with reddish-orange granules that do <i>not</i> cover the nucleus. The cytoplasm of a basophil (<b>B</b>) is packed with large purplish black granules that cover the usually bilobed nucleus. The cytoplasm of a small lymphocyte (<b>C</b>) is scant and surrounds a nucleus that is usually round (sometimes indented) and contains condensed nuclear chromatin. The cytoplasm of a monocyte (<b>D</b>) is grayish blue and contains many fine azurophilic granules and one or more clear vacuoles. The nucleus is large, eccentrically located, and either round, kidney- or horseshoe-shaped (monocyte in the picture), or lobulated. <i>(From Wickramasinghe SE, McCullough J: Blood and Bone Marrow Pathology. London, Churchill Livingstone, 2003, Fig. 1-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-012-f003.jpg" class="SCImage"><div> Peripheral blood with atypical lymphocytes. The lymphocytes are large and have abundant blue-gray cytoplasm. Nuclei are irregular and have dark chromatin with inconspicuous nucleoli. <i>(From Naeim F: Atlas of Bone Marrow and Blood Pathology. Philadelphia, WB Saunders, 2001, Fig. 13-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-012-f004.jpg" class="SCImage"><div> Schematic showing RBC count, RBC mass, plasma volume (PV), erythropoietin (EPO) concentration, and O<sub>2</sub> saturation (Sa<span style="font-variant:small-caps;">o</span><sub>2</sub>) in polycythemia and the normal (N) state: normal (<b>A</b>), relative polycythemia (<b>B</b>), appropriate absolute polycythemia (<b>C</b>), inappropriate absolute polycythemia due to ectopic production of EPO (<b>D</b>), polycythemia vera (<b>E</b>). See text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-012-f005.jpg" class="SCImage"><div> Peripheral blood in chronic myelogenous leukemia. Marked leukocytosis shows neutrophils at different stages of development (segmented and band neutrophils, metamyelocytes, and myelocytes). The cell in the center (<i>arrow</i>) depicts a basophil with dark granules in the cytosol and overlying the nucleus. Basophilia is prominent in chronic myeloproliferative diseases. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 80, Fig. 5-26.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-012-f006.jpg" class="SCImage"><div> Bone marrow with myelofibrosis: The bone marrow is replaced by fibrous tissue and the spicules are sclerotic. <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 1125, Fig. 177-6.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-012-f007.jpg" class="SCImage"><div> Peripheral blood with promyelocyte filled with Auer rods in acute promyelocytic leukemia. The neoplastic promyelocyte has numerous splinter-shaped inclusions in the cytoplasm (<i>arrow</i>) representing Auer rods. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 79, Fig. 5-21.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-012-f008.jpg" class="SCImage"><div> Peripheral blood in acute lymphoblastic leukemia. Lymphoblasts show condensed nuclear chromatin, small nucleoli, and scant cytoplasm. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, Fig. 14-5A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-012-f009.jpg" class="SCImage"><div> Peripheral blood in chronic lymphocytic leukemia. Note the increased number of lymphocytes with dense nuclear chromatin and scant cytoplasmic borders. The lymphocytes are extremely fragile and produce characteristic "smudge" cells (<i>arrows</i>) during preparation of a slide. <i>(From Hoffbrand AV: Color Atlas: Clinical Hematology, 3rd ed. St. Louis, Mosby, 2000, p 179, Fig. 10-11.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f001.jpg" class="SCImage"><div> Lymph node cortex, light micrograph (×132). The <i>white asterisk</i> shows a germinal follicle containing B cells; the <i>solid arrow</i> shows the paracortex containing T cells; and the <i>interrupted arrow</i> shows the subcapsular sinus where histiocytes are located. <i>(From Gartner L, Hiatt J: Color Textbook of Histology, 3rd ed. Philadelphia, WB Saunders, 2001, p 292, Fig. 12-8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f010.jpg" class="SCImage"><div> Urticaria pigmentosum. Note the numerous red-brown, round to oval macules and papules that are distributed over the trunk. These lesions are pruritic as a result of the release of histamine from the dermal mast cells. The lesions gradually darken over time because of increased melanin pigmentation. <i>(Courtesy of R.A. Marsden, MD, St. George's Hospital, London.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f011.jpg" class="SCImage"><div> Serum protein electrophoresis (SPE) showing a schematic of a monoclonal gammopathy. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 284, Fig. 9-1C.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f012.jpg" class="SCImage"><div> Malignant plasma cells in multiple myeloma. The majority of malignant plasma cells show a dark blue cytoplasm, peripherally located nuclei, and perinuclear clearing. Occasional cells have vacuoles containing immunoglobulin. <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 1430, Fig. 198-4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f013.jpg" class="SCImage"><div> Radiograph of a skull showing multiple "punched out" lytic lesions in multiple myeloma. When these lesions are located in other areas, such as the ribs, pathologic fractures frequently occur. <i>(From Damjanov I, Linder J: Anderson's Pathology, 10th ed. St. Louis, Mosby, 1996, p 1105, Fig. 41-61.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f014.jpg" class="SCImage"><div> Gaucher's disease. Note the fibrillary appearance of the cytoplasm in the macrophages (<i>arrow</i>). <i>(From Naeim F: Atlas of Bone Marrow and Blood Pathology. Philadelphia, WB Saunders, 2001, p 157, Fig. 11-14B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f015.jpg" class="SCImage"><div> Niemann-Pick disease. Note the soap bubble appearance of the cytoplasm in the macrophages (<i>arrow</i>). <i>(From Naeim F: Atlas of Bone Marrow and Blood Pathology. Philadelphia, WB Saunders, 2001, p 159, Fig. 11-17B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f002.jpg" class="SCImage"><div> Sites of pathologic processes in lymph nodes. Some lymphoid disorders initially localize in the germinal follicles, where B cells are located; others localize in the paracortex, where T cells are located. Mixed B- and T-cell reactions also may occur. Histiocytic disorders involve the sinuses.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f003.jpg" class="SCImage"><div> Patient with cervical lymph node. Painful nodes are usually inflammatory, while painless nodes are usually malignant. <i>(From Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 41, Fig. 81.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f004.jpg" class="SCImage"><div> Burkitt's lymphoma. The node is completely effaced with a monomorphic infiltrate of lymphocytes. Interspersed are clear spaces with reactive histiocytes containing phagocytic debris. At low power the node has a "starry sky" appearance, with the stars represented by the reactive histiocytes. This type of lymphoma is associated with a t(8;14) translocation. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1955, Fig. 21-103.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f005.jpg" class="SCImage"><div> Follicular lymphoma. Note the nodular aggregates that are present throughout the lymph node. Unlike germinal centers, these nodules are composed of a monomorphic infiltrate of lymphoma cells. This type of lymphoma is associated with the t(14;18) translocation leading to overexpression of the BCL-2 protein product (antiapoptosis gene). <i>(Courtesy of Dr. Robert W. McKenna, Department of Pathology, University of Texas Southwestern Medical School, Dallas, Texas.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f006.jpg" class="SCImage"><div> Classic Reed-Sternberg (RS) cell. The large, multilobed cell with prominent nucleoli is surrounded by a halo of clear nucleoplasm. Classic RS cells are more easily found in mixed-cellularity Hodgkin's lymphoma than in lymphocyte-predominant and nodular-sclerosing Hodgkin's lymphoma. <i>(From Damjanov I, Linder J: Anderson's Pathology, 10th ed. St. Louis, Mosby, 1996, p 1145, Fig. 42-47A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f007.jpg" class="SCImage"><div> Nodular-sclerosing Hodgkin's lymphoma. The lymphoid nodule is encased by fibrous tissue. Note the spaces in the nodule within which are Reed-Sternberg variants called lacunar cells. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1924, Fig. 21-56.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f008.jpg" class="SCImage"><div> Electron micrograph showing racket shaped Birbeck granules in a histiocyte. (Courtesy of William Meek, Professor and Vice Chairman of Anatomy and Cell Biology, Oklahoma State University, Center for Health Sciences, Tulsa, Oklahoma.)</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-013-f009.jpg" class="SCImage"><div> Child with Letterer-Siwe disease (Langerhans histiocytosis). Note the eczematous type rash over the body surface due to malignant histiocytes infiltrating the skin and dermis. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1249, Fig. 25-18A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-014-f001.jpg" class="SCImage"><div> Coagulation cascade. Both the extrinsic and intrinsic coagulation systems use the final common pathway for the formation of a fibrin clot. a, activated; HMWK, high-molecular-weight kininogen; PF3, platelet factor 3.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-014-f002.jpg" class="SCImage"><div> Small vessel hemostasis response to injury. See the text for discussion. TXA<sub>2</sub>, thromboxane A<sub>2</sub>; vWD, von Willebrand disease; vWF, von Willebrand factor.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-014-f003.jpg" class="SCImage"><div> Prothrombin time (PT) and partial thromboplastin time (PTT). See the text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-014-f004.jpg" class="SCImage"><div> Petechiae in idiopathic thrombocytopenic purpura showing pinpoint hemorrhages, a sign of platelet dysfunction, in the skin over the thorax and shoulders. When touched, petechiae do not blanch with pressure. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, Fig. 10-10.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-014-f005.jpg" class="SCImage"><div> Senile purpura showing the large, irregular areas of hemorrhage on the backs of both hands. This benign condition primarily occurs in body areas that are frequently traumatized. It is due to the normal vessel instability that is associated with aging. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, Fig. 10-112.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-015-f001.jpg" class="SCImage"><div> Possible children phenotypes if father is BO and mother is AO. See text for discussion. <i>(Adapted from Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-015-f002.jpg" class="SCImage"><div> Forward and back type to identify ABO blood groups. Forward type identifies the blood group antigen by reacting anti-A and anti-B against patient RBCs. Back type identifies the natural antibodies in the patient serum by reacting A RBCs and B RBCs against the patient serum. Refer to the text for discussion of the blood groups and their natural antibodies.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-015-f003.jpg" class="SCImage"><div> Possible Rh phenotypes in children if the father is cde/CDE and the mother is cDE/CDE. See text for discussion. <i>(Adapted from Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-015-f004.jpg" class="SCImage"><div> ABO and Rh hemolytic disease of the newborn. See text for discussion. <i>(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998, Fig. 14-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-015-f005.jpg" class="SCImage"><div> Cross section of the brain of a newborn with kernicterus. <i>Arrows</i> depict yellow bilirubin pigment deposited in the basal ganglia. Bilirubin is toxic to neurons and produces long-term neurologic sequelae. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 487, Fig. 10-16.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f001.jpg" class="SCImage"><div> Spirometry showing normal lung volumes and capacities and forced expiratory volume at 1 second (FEV<sub>1 sec</sub>) and forced vital capacity (FVC) findings in a normal person (A), a person with restrictive lung disease (B), and a person with obstructive lung disease (C). ERV, expiratory reserve volume; FRC, functional residual capacity; RV, residual volume; TLC, total lung capacity; TV, tidal volume; VC, vital capacity. <i>(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998, p 229, Fig. 11-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f010.jpg" class="SCImage"><div> <b>A,</b> Parainfluenza virus producing laryngotracheobronchitis. Frontal radiograph showing narrowing of the trachea (<i>arrows</i>) producing the classic steeple sign. <b>B,</b> Cytomegalovirus. The enlarged nuclei of many of the type I pneumocytes contain large inclusions (basophilic staining with hematoxylin and eosin stain) surrounded by a clear halo. <b>C,</b> Tonsillitis due to <i>Corynebacterium diphtheriae</i>. Note the gray, pseudomembrane covering the tonsils. <b>D,</b> <i>Cryptococcus neoformans</i>. The yeast form produces a clear capsule around a central faint nucleus. <b>E,</b> <i>Aspergillus fumigatus</i>. Lung biopsy stained with Gomori methenamine-silver shows septated hyphae and fruiting body (<i>inset</i>). <b>F,</b> <i>Coccidioides immitis</i>. Note the spherules containing endospores (<i>arrow</i>). <b>G,</b> <i>Histoplasma capsulatum</i>. Laminated granuloma at the lung periphery produces puckering of the pleural surface. <b>H,</b> <i>Histoplasma capsulatum</i>. Alveolar macrophage contains intracellular yeast forms. <b>I,</b> <i>Blastomyces dermatidis</i>. Note the yeast forms with broad-based buds (<i>arrow</i>). <i>(<b>A</b> from Pretorius ES, Solomon JA: Radiology Secrets, 2nd ed. St. Louis, Mosby, 2006, p 464, Fig. 57-4; <b>B</b> from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 56, Fig. 4-24; <b>C</b> courtesy of Franklin H. Top, Department of Hygiene and Preventive Medicine, State University of Iowa College of Medicine, Iowa City, Iowa, and Parke, Davis & Company's Therapeutic Notes; <b>D</b> and <b>F</b> from Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, pp 127, 126, Figs. 5-92, 5-91 on right, respectively; <b>E</b>, <b>G</b>, <b>I</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, pp 400, 754, 755, Figs. 8-49B, 15-37, 15-39A, respectively; <b>H</b> from Murray PR, Shea YR: Medical </i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f011.jpg" class="SCImage"><div> Primary tuberculosis. Note the tan-yellow subpleural granuloma with caseation necrosis and the tan-yellow area of caseation necrosis in the hilar lymph node in the mid-lung field. The two of these together is called a Ghon complex. The inset shows an acid-fast stain with numerous <i>Mycobacterium tuberculosis</i> organisms. <i>(The gross picture of primary tuberculosis is from Klatt, E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 197, Fig. 8-4; inset from Hoffbrand AV: Color Atlas: Clinical Hematology, 3rd ed. St. Louis, Mosby, 2000, p 136, Fig. 7-85B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f012.jpg" class="SCImage"><div> Reactivation tuberculosis. The apices of both lungs show gray-white areas of caseation necrosis and multiple areas of cavitation. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 386, Fig. 8-32.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f013.jpg" class="SCImage"><div> Lung abscess. Note the large abscess spanning the right upper and lower lobes. It is filled with necrotic material. <i>(From Corrin B: Pathology of the Lungs. London, Churchill Livingstone, 2000, p 172, Fig. 5.5.16.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f014.jpg" class="SCImage"><div> Lung abscess. The chest computed tomographic scan shows an abscess in the right lower lobe with an air-fluid level. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 121, Fig. 5-74.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f015.jpg" class="SCImage"><div> Saddle embolus occluding the main branches of the pulmonary artery. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 57, Fig. 4-26.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f016.jpg" class="SCImage"><div> Radionuclide perfusion scan in the lung. The radionuclide scan shows multiple perfusion defects in both lungs (<i>arrows</i>) due to multiple pulmonary emboli. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. Philadelphia, Mosby, 2003, Fig. 4-49.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f017.jpg" class="SCImage"><div> Cor pulmonale. Note the increased ventricular volume and hypertrophied muscle of the right ventricle (<i>arrow</i>). The patient had pulmonary hypertension.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f018.jpg" class="SCImage"><div> Coal worker's pneumoconiosis. Note the heavy anthracotic pigment deposition in the fibrotic tissue. Subjacent alveoli are dilated. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 113, Fig. 5-48.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f019.jpg" class="SCImage"><div> Silicosis. Note the nodular fibrotic mass in the lung. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 113, Fig. 5-49.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f002.jpg" class="SCImage"><div> Flow-volume loop. See text for discussion. PEF, peak expiratory flow; RV, residual volume; TLC, total lung capacity; VC, vital capacity. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 71, Fig. 3-3.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f020.jpg" class="SCImage"><div> Asbestos body. The straight, golden-brown, beaded asbestos body represents an asbestos fiber coated by iron and protein. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 65, Fig. 4-51B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f021.jpg" class="SCImage"><div> Malignant mesothelioma encases the lung and invades locally into the lung parenchyma. <i>(From Corrin B: Pathology of the Lungs. London, Churchill Livingstone, 2000, p 619, Fig. 14.8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f022.jpg" class="SCImage"><div> Sarcoid granuloma showing pink-staining epithelioid cells and foreign body type of multinucleated giant cells. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 738, Fig. 15-23.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f023.jpg" class="SCImage"><div> Types of emphysema. <b>A</b> The schematic shows a normal distal airway, including a terminal bronchiole (TB) leading into the respiratory unit consisting of a respiratory bronchiole (RB), alveolar duct (AD), and alveoli (ALV). Elastic fibers apply radial traction to keep these airways open. <b>B</b> Centriacinar (centrilobular) emphysema is characterized by trapping of air in the respiratory bronchioles. Note how the elastic fibers of the distal TB are destroyed, causing obstruction to airflow. This causes the trapped air to distend the RBs, whose elastic tissue support is destroyed. <b>C</b> Panacinar emphysema is characterized by trapping of air in the entire respiratory unit behind the collapsed TB.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f024.jpg" class="SCImage"><div> Centriacinar (centrilobular emphysema). The enlarged spaces in the lung parenchyma are air-filled respiratory bronchioles that have lost their elastic tissue support. <i>(Reproduced by permission of the late Professor B.E. Heard, Brompton, UK.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f025.jpg" class="SCImage"><div> Panacinar emphysema. The enlarged spaces in the lung parenchyma are air-filled respiratory bronchioles, alveolar ducts, and alveoli that have lost their elastic tissue support. <i>(Reproduced by permission of the late Professor B.E. Heard, Brompton, UK.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f026.jpg" class="SCImage"><div> Chest radiograph in emphysema showing a vertically oriented heart (<i>arrow</i>) and depressed diaphragm. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 186, Fig. 4-94.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f027.jpg" class="SCImage"><div> Bronchiectasis showing dilated airways filled with pus. <i>(From Corrin B: Pathology of the Lungs. London, Churchill Livingstone, 1999, p 85, Fig. 3-5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f028.jpg" class="SCImage"><div> Computed tomographic scan showing bronchiectasis in both lungs. Note the dilated cystic to saccular appearing airways. <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 633, Fig. 90-2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f029.jpg" class="SCImage"><div> Schematic showing defect in cystic fibrosis transmembrane regulator (CFTR) in cystic fibrosis (CF) in sweat glands (<b>A</b>) and epithelial cells (<b>B</b>). See text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f003.jpg" class="SCImage"><div> Flow-volume loops in normal person, obstructive disorder (A), restrictive disorder (B). See text for discussion. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 72, Fig. 3-4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f030.jpg" class="SCImage"><div> <b>A</b> Sputum cytology in squamous cell carcinoma. Note the orange-staining, keratinized squamous carcinoma cells with irregular, hyperchromatic nuclei (<i>arrow</i>). <b>B</b> Fine needle aspirate of a lymph node with metastatic small cell carcinoma of lung. Note the cluster of cells with hyperchromatic nuclei and scant cytoplasm. <b>C</b> Primary lung cancer arising in a central bronchus and extending into the lumen. Note that the lumen is obstructed by gray-white tumor causing distal bronchiectasis (<i>solid arrow</i>) and obstructive pneumonia (<i>interrupted arrow</i>). <b>D</b> Chest radiograph of bronchogenic carcinoma presenting as a central right hilar mass (<i>arrow</i>). <b>E</b> Peripheral adenocarcinoma with scar retracting the pleural surface (scar carcinoma). The black pigment is anthracotic pigment. <b>F</b> Chest radiograph of bronchogenic carcinoma presenting as a mass in the periphery of the right upper lobe (<i>arrow</i>). <i>(<b>A</b> and <b>B</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 760, Figs. 15-43A, 15-43B, respectively; <b>C</b> and <b>E</b> from Corrin B: Pathology of the Lungs. London, Churchill Livingstone, 1999, pp 463, 472, Figs. 13-1.5, 13-1.13B, respectively; <b>D</b> and <b>F</b> from Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, pp 90, 89, Figs. 13-7, 13-6, respectively.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f031.jpg" class="SCImage"><div> Metastatic renal cell carcinoma showing multiple nodular lesions scattered throughout the lung parenchyma. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 766, Fig. 15-47.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f032.jpg" class="SCImage"><div> Chest radiograph showing multiple metastatic nodules throughout both lung fields. <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 600, Fig. 84-9.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f033.jpg" class="SCImage"><div> Horner's syndrome in right eye. Note the mild lid lag and miotic pupil when compared to the left eye. <i>(Courtesy of Shannath Merbs, MD, The Wilmer Ophthalmological Institute, Johns Hopkins University.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f034.jpg" class="SCImage"><div> Superior vena caval syndrome. Note distention of the veins over the front of the chest. <i>(From Corrin B: Pathology of the Lungs. London, Churchill Livingstone, 1999, p 464, Fig. 13-1-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f035.jpg" class="SCImage"><div> Frontal chest radiograph showing a right pleural effusion. Note the blunting of the right costophrenic angle and obscuration of the right hemidiaphragm. <i>(From Pretorius ES, Solomon JA: Radiology Secrets, 2nd ed. St. Louis, Mosby, 2006, p 539, Fig. 66-2A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f036.jpg" class="SCImage"><div> Left tension pneumothorax. Note the margin of the lung in the left pleural cavity and the tracheal deviation to the right (<i>arrow</i>). <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 601, Fig. 84-11.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f004.jpg" class="SCImage"><div> Nasal polyp. Note the gray-white mass in the left nasal cavity. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 312, Fig. 11-24.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f005.jpg" class="SCImage"><div> Laryngeal squamous cell carcinoma involving the right vocal cord (<i>arrow</i>). <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 47, Fig. 3-16.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f006.jpg" class="SCImage"><div> Electron micrograph of a type II pneumocyte showing a lamellar body (<i>arrow</i>) containing surfactant. <i>(From Corrin B: Pathology of the Lungs. London, Churchill Livingstone, 1999, p 15, Fig. 1-26.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f007.jpg" class="SCImage"><div> Neonatal respiratory distress syndrome. Some of the dilated respiratory bronchioles and alveolar ducts are lined with a fibrin-rich membrane (hyaline membrane) (<i>arrow</i>). The subjacent alveoli are collapsed. <i>(From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 128, Fig. 5-25.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f008.jpg" class="SCImage"><div> Chest radiograph in respiratory distress syndrome. Note the fine, uniform granularity distributed throughout both lungs ("ground glass" appearance). <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 380, Fig. 2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-016-f009.jpg" class="SCImage"><div> <b>A</b> Gram stain of <i>Streptococcus pneumoniae</i>. The sputum stain shows numerous lancet-shaped diplococci with the tapered ends pointing to each other. A few neutrophils contain phagocytosed bacteria. <b>B</b> Bronchopneumonia showing patchy areas of consolidation (<i>arrows</i>) representing collections of neutrophils in the alveoli and bronchi. <b>C</b> Lobar pneumonia. The lower lobe is uniformally consolidated. <b>D</b> Posteroanterior radiograph of a right lower lobe pneumococcal pneumonia. Note the alveolar consolidation and the visible border of the right ventricle indicating that the middle lobe is <i>not</i> involved. <i>(<b>A</b> from Henry JB: Clinical Diagnosis and Management by Laboratory Methods, 20th ed. Philadelphia, WB Saunders, 2001, Plate 50-1; <b>B</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 749, Fig. 15-33; <b>C</b> from Corrin B: Pathology of the Lungs. London, Churchill Livingstone, 2000, p 162, Fig. 5.2.5; <b>D</b> from Kliegman RM, Jenson HB, Behrman RE, Stanton BF: Nelson Textbook of Pediatrics, 18th ed. Philadelphia, Saunders Elsevier, 2007, p 1798, Fig. 397-2A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f001.jpg" class="SCImage"><div> Cleft palate. Note the defect in the palate (<i>arrow</i>). <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 68, Fig. 10-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f010.jpg" class="SCImage"><div> Barium study of the esophagus in achalasia. Note dilated esophagus ending in a narrowed esophagogastric junction ("birds-beak" appearance) (<i>arrow</i>). <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 106, Fig. 16-6.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f011.jpg" class="SCImage"><div> Distal adenocarcinoma of the esophagus. Note the raised lesion at the junction of the distal esophagus and proximal stomach (<i>arrow</i>). <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 109, Fig. 16-12 [right].)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f012.jpg" class="SCImage"><div> Midesophagus squamous cell carcinoma. Note the elevated round nodular mass with a central area of ulceration. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 626, Fig. 11-14C.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f013.jpg" class="SCImage"><div> Silver stain showing <i>Helicobacter pylori</i> organisms in the mucus layer lining the gastric epithelial cells. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 815, Fig. 17-15.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f014.jpg" class="SCImage"><div> Chronic atrophic gastritis of the distal stomach secondary to <i>Helicobacter pylori</i>. The <i>arrow</i> shows clear spaces in the mucosal epithelium representing goblet cells, which are normally present in the intestine. Note the heavy lymphocytic infiltrate throughout all layers of the stomach. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 815, Fig. 17-14.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f015.jpg" class="SCImage"><div> Plain abdominal radiograph in a supine patient with a perforated peptic ulcer. Note the presence of air under both diaphragms. <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 1015, Fig. 142-3.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f016.jpg" class="SCImage"><div> Gastric adenocarcinoma showing an irregular ulcer crater with piling up of the mucosa around the ulcer. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 825, Fig. 17-26.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f017.jpg" class="SCImage"><div> Diffuse type of gastric adenocarcinoma with signet-ring carcinoma cells (<i>arrows</i>). Mucin produced by the cancer cells pushes the nucleus to the periphery. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 825, Fig. 17-27B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f018.jpg" class="SCImage"><div> <b>A,</b> <i>Clostridium</i> species. Gram-positive rods. <b>B,</b> Cryptosporidiosis. Note the small round oocysts of <i>Cryptosporidium parvum</i> lining the luminal surface of the small intestine. <b>C,</b> <i>Entamoeba histolytica</i> trophozoites showing erythrophagocytosis (<i>arrow</i>). <b>D,</b> <i>Giardia lamblia</i> with two nuclei and flagella. <b>E,</b> Embryonated eggs of <i>Enterobius vermicularis</i>. <b>F,</b> <i>Strongyloides stercoralis</i>. Larvae in stool sample. <i>(<b>A</b> and <b>F</b> from Murray PR, Shea YR: Medical Microbiology, 2nd ed. St. Louis, Mosby, 2002, pp 402, 887, Figs. 40-1, 84-9, respectively; <b>B</b> from Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 175, Fig. 7-69; <b>C</b> and <b>D</b> from Henry JB: Clinical Diagnosis and Management by Laboratory Methods, 20th ed. Philadelphia, WB Saunders, 2001, Plate 55-7C, Plate 55-8C, respectively; <b>E</b> from Hart P, Shears CT: Color Atlas of Medical Microbiology. St. Louis, Mosby, 1996, p 271, Fig. 446.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f019.jpg" class="SCImage"><div> Dermatitis herpetiformis showing vesicles with erythema on the extensor surface of the forearm. Presence of this lesion has a strong association with underlying celiac disease. <i>(From Savin JAA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, p 92, Fig. 3.25.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f002.jpg" class="SCImage"><div> <b>A</b> Exudative tonsillitis. Note the gray-white pus in the tonsillar crypts (<i>arrow</i>). <b>B</b> Hairy leukoplakia along the lateral border of the tongue. It is a glossitis due to Epstein-Barr virus and is a pre-AIDS-defining lesion. <b>C</b> Herpes simplex type 1. Note the clusters of vesicles around the vermilion border of the upper and lower lips. <b>D</b> Actinomycosis. Note the colony of <i>Actinomyces</i> (sulfur granule) surrounded by an inflammatory infiltrate. <b>E</b> Notched teeth in congenital syphilis. <b>F</b> Oral thrush. Note the extensive white "curd-like" plaque that can be wiped off leaving an erythematous base. <i>(<b>A</b> courtesy of Edward L. Applebaum, MD, Department of Otolaryngology, University of Illinois, Urbana, Illinois; <b>B</b> from Lookingbill D, Marks J: Principles of Dermatology, 3rd ed. Philadelphia, WB Saunders, 2000, p 338, Fig. 23-7; <b>C</b> from Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 333, Fig. 12-10; <b>D</b> from Corrin B: Pathology of the Lungs. London, Churchill Livingstone, 2000, p 195, Fig. 5.3.15; <b>E</b> from Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 11, Fig. 21; <b>F</b> from Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 65, Fig. 10-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f020.jpg" class="SCImage"><div> Celiac disease showing atrophy of the villi, lengthening of the crypts, and a heavy chronic inflammatory infiltrate in the lamina propria. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 128, Fig. 7-25A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f021.jpg" class="SCImage"><div> Radiograph showing small bowel obstruction. Multiple air-fluid levels are present (<i>arrows</i>) in dilated small bowel. There is absence of air distal to the obstruction. <i>(From Katz DS: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 117, Fig. 25-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f022.jpg" class="SCImage"><div> Plain film of the abdomen showing a dilated stomach and duodenal bulb ("double bubble" sign) in a patient with duodenal atresia. <i>(From Pretorius ES, Solomon JA: Radiology Secrets, 2nd ed. St. Louis, Mosby, 2006, p 467, Fig. 58-2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f023.jpg" class="SCImage"><div> Schematic of intussusception and volvulus. See text for discussion. <i>(From Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 605, Fig. 15-26.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f024.jpg" class="SCImage"><div> Schematic of direct inguinal hernia. See text for discussion. <i>(From Moore NA, Roy WA: Rapid Review Gross and Developmental Anatomy, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 69, Fig. 3-5 A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f025.jpg" class="SCImage"><div> Schematic of indirect inguinal hernia. See text for discussion. <i>(From Moore NA, Roy WA: Rapid Review Gross and Developmental Anatomy, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 69, Fig. 3-5B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f026.jpg" class="SCImage"><div> Hemorrhagic infarction of small bowel, showing the diffuse dark discoloration of the small bowel. Arrow shows a thrombosed superior mesenteric artery attached to the aorta. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 124, Fig. 7-8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f027.jpg" class="SCImage"><div> Single contrast barium enema showing "thumb-printing" of the colonic mucosa (<i>arrows</i>) in the region of the splenic flexure in ischemic colitis. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 202, Fig. 26-9.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f028.jpg" class="SCImage"><div> Colonoscopic view of the cecum showing an area of mucosal bleeding from a ruptured telangiectatic vessel in angiodysplasia. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 202, Fig. 26-8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f029.jpg" class="SCImage"><div> Meckel diverticulum located on the antimesenteric side of the small intestine. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 830, Fig. 17-31.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f003.jpg" class="SCImage"><div> Apthous ulcer. Note the ulcerated surface on the lip covered by a shaggy gray exudate. <i>(From Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 35, Fig. 69.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f030.jpg" class="SCImage"><div> Gross section of sigmoid colon showing pulsion diverticula with fecal material (fecaliths). <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 183, Fig. 7-94.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f031.jpg" class="SCImage"><div> Sigmoid diverticulosis viewed on barium enema. Multiple diverticula sacs (<i>arrows</i>) are outlined by the double-contrast barium technique. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 382, Fig. 8-110.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f032.jpg" class="SCImage"><div> Ulcerative colitis. The colon shows diffuse ulceration of the mucosal surface and residual islands of inflamed mucosa (pseudopolyps). <i>(From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 271, Fig. 10-10A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f033.jpg" class="SCImage"><div> Ulcerative colitis. Note the linear ulcers and islands of residual mucosa called pseudopolyps. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 179, Fig. 7-81.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f034.jpg" class="SCImage"><div> Crohn's disease, showing a resection of the terminal ileum with attached cecum and appendix; the appendix is to the left. The thickened terminal ileal wall causes the narrowing (<i>arrow</i>) at the junction of the ileum and the cecum. The ileal mucosa has a cobblestone appearance due to linear ulcerations (aphthous ulcers) that cut into the underlying submucosa. <i>(From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 271, Fig. 10-10B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f035.jpg" class="SCImage"><div> Crohn's disease. Note the inflammatory infiltrate in the muscle layer of the large intestine with occasional multinucleated giant cells (<i>arrow</i>) representing a granuloma. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 134, Fig. 7-41.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f036.jpg" class="SCImage"><div> Carcinoid tumor (CT) of the vermiform appendix. Note the yellow mass in the wall of the appendix (<i>arrow</i>). The lumen contains fecaliths (F). <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 196, Fig. 25-20.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f037.jpg" class="SCImage"><div> Tubular adenoma. The head of the stalked polyp has a lobulated, mushroom-like appearance. <i>Arrow</i> points to the stalk. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 138, Fig. 7-55.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f038.jpg" class="SCImage"><div> Villous adenoma. Note the large cauliflower-like mass in the rectosigmoid. These tumors secrete mucus rich in potassium and protein. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 803, Fig. 11-197A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f039.jpg" class="SCImage"><div> Familial polyposis. Note the numerous small, sessile polyps. These were present in the entire large bowel. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 802, Fig. 11-195.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f004.jpg" class="SCImage"><div> Peutz-Jeghers syndrome. Note the melanin pigmentation on the lips. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 334, Fig. 12-12.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f040.jpg" class="SCImage"><div> Adenocarcinoma of the sigmoid colon. Resection of the rectosigmoid shows an annular and ulcerating growth, causing a stricture. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 139, Fig. 7-61.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f041.jpg" class="SCImage"><div> Spot radiograph from a single contrast phase of a double contrast barium enema showing an adenocarcinoma of the rectum with circumferential narrowing of the lumen ("apple core" lesion). <i>(From Pretorius ES, Solomon JA. Radiology Secrets, 2nd ed. St. Louis, Mosby, 2006, p 125, Fig. 15-9.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f042.jpg" class="SCImage"><div> Acute appendicitis showing erythema and vascular congestion of the serosal surface of the appendix. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 131, Fig. 7-30.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f043.jpg" class="SCImage"><div> Prolapsed internal hemorrhoids. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier,2006, p 510, Fig. 17-33.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f005.jpg" class="SCImage"><div> Leukoplakia of the tongue with invasive squamous cell carcinoma. Discrete raised white patches are evident on both sides of the tongue. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 362, Fig. 8-28.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f006.jpg" class="SCImage"><div> Erythroplakia. Note the raised erythematous area (<i>arrow</i>) on the palate. <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 1451, Fig. 200-2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f007.jpg" class="SCImage"><div> Squamous cell carcinoma of the lower lip. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 67, Fig. 10-5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f008.jpg" class="SCImage"><div> Tracheoesophageal fistula. The proximal esophagus ends blindly, and the distal esophagus arises from the trachea. The stomach is distended with air owing to communication of the esophagus with the trachea.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-017-f009.jpg" class="SCImage"><div> Esophageal varices, showing many linear-oriented dilated and tortuous veins in the submucosa of the distal esophagus. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 110, Fig. 6-23A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f001.jpg" class="SCImage"><div> Bilirubin metabolism. Refer to the text for discussion. RBC, red blood cell; UGT, uridine glucuronosyltransferase.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f010.jpg" class="SCImage"><div> Spider angioma (telangiectasia) showing a single central arteriole and numerous radiating capillaries. <i>(From Gitlin M, Strauss R: Atlas of Clinical Hepatology. Philadelphia, WB Saunders, 1995, p 3, Fig. 1.4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f011.jpg" class="SCImage"><div> Liver biopsy stained with Prussian blue in a patient with hereditary hemochromatosis. The hepatocytes are filled with blue iron granules. This is an early stage before parenchymal damage and fibrosis develop. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 910, Fig. 18-28.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f012.jpg" class="SCImage"><div> Kayser-Fleischer ring. The <i>arrow</i> depicts deposition of a copper-colored pigment in Descemet's membrane in the cornea. <i>(From Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, p 151, Fig. 8-15.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f013.jpg" class="SCImage"><div> α<sub>1</sub>-Antitrypsin deficiency. The globules are periodic acid-Schiff positive. <i>(From MacSween R, Burt A, Portmann B, et al: Pathology of the Liver, 4th ed. London, Churchill Livingstone, 2002, p 176, Fig. 4-21.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f014.jpg" class="SCImage"><div> Hepatocellular carcinoma. Multiple large, hemorrhagic tumor masses are present in the liver (<i>arrows</i>). There is also diffuse infiltration of tumor blending in with the remaining liver. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 161, Fig. 8-70.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f015.jpg" class="SCImage"><div> Yellow cholesterol stones with centers containing entrapped bile pigments. The wall of the gallbladder is scarred. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 930, Fig. 18-50.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f016.jpg" class="SCImage"><div> Black pigmented stones. These types of stones are usually a sign of a chronic extravascular hemolytic anemia where there is an increase in calcium bilirubinate in bile. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 931, Fig. 18-51.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f017.jpg" class="SCImage"><div> Ultrasound showing gallstones (<i>arrow</i>). <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 1158, Fig. 159-5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f018.jpg" class="SCImage"><div> Grey-Turner sign. Note the purplish discoloration in the loins due to tracking of hemorrhagic necrotic pancreatic material along the retroperitoneal planes. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 162, Fig. 22-5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f019.jpg" class="SCImage"><div> Cullen's sign. Note the hemorrhagic discoloration around the umbilicus. It is due to tracking of hemorrhagic necrotic pancreatic tissue around the falciform and umbilical ligaments. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 162, Fig. 22-4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f002.jpg" class="SCImage"><div> Scleral icterus. Note the yellowish discoloration of the sclera. <i>(From Savin J, Hunter JA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, Fig. 6.28.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f020.jpg" class="SCImage"><div> Pancreatic adenocarcinoma. Yellow tumor has extensively replaced the pancreas. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 226, Fig. 9-14.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f003.jpg" class="SCImage"><div> Serologic markers in hepatitis B. Anti-HBc, anti-HBV core antigen; anti-HBe, anti-HBV e antigen; anti-HBs, anti-HBV surface antibody; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; IgG, immunoglobulin G; IgM, immunoglobulin M.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f004.jpg" class="SCImage"><div> Hydatid cyst. A single cyst in the liver shows numerous daughter cysts containing larval forms. <i>(From MacSween R, Burt A, Portmann B, et al: Pathology of the Liver, 4th ed. London, Churchill Livingstone, 2002, p 388, Fig. 8-35.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f005.jpg" class="SCImage"><div> Centrilobular hemorrhagic necrosis ("nutmeg" liver). The liver has a mottled cut surface. Dark areas represent congested central veins and sinusoids. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 146, Fig. 8-8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f006.jpg" class="SCImage"><div> Cholestasis. Note the dilated bile ductules filled with yellowish-green bile. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 199, Fig. 8-11.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f007.jpg" class="SCImage"><div> Alcoholic cirrhosis, showing diffuse micronodular surface of the liver. The regenerative nodules are surrounded by collagen. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 154, Fig. 8-42.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f008.jpg" class="SCImage"><div> Micronodular cirrhosis with regenerative nodules (red) surrounded by dense binds of fibrous tissue (blue). <i>(From MacSween R, Burt A, Portmann B, et al: Pathology of the Liver, 4th ed. London, Churchill Livingstone, 2002, p 599, Fig. 13-20.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-018-f009.jpg" class="SCImage"><div> Patient with cirrhosis. Note abdominal distention due to ascites. Signs of hyperestrinism include gynecomastia and a female distribution of hair (hair does not extend to umbilicus). <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 133, Fig. 20-2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f001.jpg" class="SCImage"><div> Blood urea nitrogen (BUN) and creatinine (Cr) ratios in normal persons (<b>A</b>), and in prerenal (<b>B</b>), renal (<b>C</b>), and postrenal azotemia (<b>D</b>). See text for discussion.<i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 102, Fig. 4-15.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f010.jpg" class="SCImage"><div> Chronic pyelonephritis. The renal cortex shows deep U-shaped scars. Sections through this scar would have revealed a blunt calyx. <i>(From Kern WF, Silva FG, Kern W [eds]: Atlas of Renal Pathology. Philadelphia, WB Saunders, 1999, p 149, Fig. 13-16.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f011.jpg" class="SCImage"><div> Analgesic nephropathy showing multiple brownish necrotic papillae (<i>arrows</i>). <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1003, Fig. 20-45.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f012.jpg" class="SCImage"><div> Benign nephrosclerosis showing a finely granular cortical surface due to atrophy of tubules, glomerular sclerosis, and interstitial fibrosis in the renal cortex. <i>(From Kern WF, Silva FG, Laszik ZG, et al [eds]: Atlas of Renal Pathology. Philadelphia, WB Saunders, 1999, p 166, Fig. 14-10.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f013.jpg" class="SCImage"><div> Malignant hypertension. A feature of malignant hypertension is hyperplastic arteriolosclerosis due to smooth muscle hyperplasia and basement membrane reduplication giving the vessel an "onion skin" appearance. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelpha, WB Saunders, 2006, p 7, Fig. 1-17.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f014.jpg" class="SCImage"><div> Hydronephrosis of the kidney. There is marked dilation of the renal pelvis and calyces with thinning of the overlying cortex and medulla due to compression atrophy. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1013, Fig. 20-56.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f015.jpg" class="SCImage"><div> Staghorn calculi. Note the staghorn calculi in the renal calyces and the renal pelvis. <i>(From Kern WF, Silva FG, Laszik ZG, et al [eds]: Atlas of Renal Pathology. Philadelphia, WB Saunders, 1999, p 155, Fig. 13-30.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f016.jpg" class="SCImage"><div> Renal cell carcinoma. The large, yellow upper pole mass with multifocal areas of hemorrhage extends into the renal pelvis. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 234, Fig. 11-79.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f017.jpg" class="SCImage"><div> Renal cell carcinoma: This microscopic section of a renal cell carcinoma shows cells with a clear cytoplasm. <i>(From Kern WF, Silva FG, Laszik ZG, et al [eds]: Atlas of Renal Pathology. Philadelphia, WB Saunders, 1999, p 281, Fig. 23-5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f002.jpg" class="SCImage"><div> <b>A,</b> Dysmorphic RBCs. This phase-contrast microscopy of urine sediment shows dysmorphic RBCs (<i>arrows</i>) with protrusions from the RBC membrane related to damage from glomerular inflammation. They are a sign of hematuria of glomerular origin. <b>B,</b> Sediment with neutrophils. The <i>arrow</i> points to a bilobed neutrophil. <b>C,</b> Oval fat body under polarization showing classic Maltese crosses. The Maltese crosses are due to cholesterol, which is always increased in the nephrotic syndrome. <b>D,</b> Hyaline casts. The <i>arrows</i> show two hyaline casts that are acellular and have smooth borders. <b>E,</b> RBC cast in the urine. Note the cylindrical cast composed of red-staining cells. <b>F,</b> White blood cell cast. The cast is filled with multilobed cells (<i>arrow</i>) representing neutrophils. These casts are seen in acute pyelonephritis and acute drug-induced tubulointerstitial nephritis. <b>G,</b> Renal tubular cell cast. The cast has numerous renal tubular cells with round nuclei (<i>arrows</i>). These casts are a sign of acute tubular necrosis. <b>H,</b> Waxy/broad cast in the urine sediment. The diameter of the cast is increased due to tubular atrophy. It has a refractile quality, with distinct margins. <i>Arrows</i> show degenerating renal tubular cells. <i>(<b>A</b> and <b>E</b> from Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 276, Figs. 6.10, 6.11, respectively; <b>B, C, D, F, G,</b> and <b>H</b> from Henry JB: Clinical Diagnosis and Management by Laboratory Methods, 20th ed. Philadelphia, WB Saunders, 2001, Plates 18-4, 18-12, 18-13A, 18-17, 18-11, 18-14, respectively.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f003.jpg" class="SCImage"><div> Schematic of a normal glomerulus. See text for discussion. <i>(Modified and reproduced with permission from Striker LJ, Olson JL, Striker GL: The Renal Biopsy, 2nd ed. Philadelphia, WB Saunders, 1990.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f004.jpg" class="SCImage"><div> Horseshoe kidney. Note that the lower poles of the kidneys are fused. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 211, Fig. 11-3.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f005.jpg" class="SCImage"><div> Renal dysplasia. Note the multicystic deformed kidney and dilated ureter. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 213, Fig. 11-11.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f006.jpg" class="SCImage"><div> Adult polycystic kidney disease. There is complete effacement of normal kidney architecture by cysts within the cortex and medulla of both kidneys. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 212, Fig. 11-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f007.jpg" class="SCImage"><div> <b>A,</b> Normal glomerulus. <b>B,</b> Linear immunofluorescence. The uninterrupted smooth immunofluorescence along the glomerular basement membrane is caused by deposition of IgG antibodies directed against the membrane (e.g., Goodpasture syndrome). <b>C,</b> Granular immunofluorescence. Granular irregular deposits in the capillaries are caused by immunocomplex deposition (e.g., poststreptococcal glomerulonephritis). <b>D,</b> Fusion of the podocytes. <i>Arrow</i> shows fusion of the podocytes. This finding occurs in all glomerular diseases that present with the nephrotic syndrome (e.g., minimal change disease). <b>E,</b> Subendothelial immunocomplex deposits viewed with electron microscopy. The band of electron-dense material extends around the glomerular basement membrane and hugs the interface of the membrane with the capillary lumen. The <i>arrow</i> points to immune deposits directly beneath the nucleus of the endothelial cell. A thin rim of normal basement membrane (light gray) separates the deposits from the epithelial side of the membrane. The patient had diffuse proliferative glomerulonephritis due to systemic lupus erythematosus. <b>F,</b> Subepithelial immunocomplex deposits viewed with electron microscopy. <i>Arrows</i> point to electron-dense deposits directly beneath the visceral epithelial cells in a patient with poststreptococcal glomerulonephritis. The normal basement membrane has a light gray appearance. <b>G,</b> Poststreptococcal diffuse proliferative glomerulonephritis. The glomerulus is hypercellular due to an increase in neutrophils and mesangial cells. <b>H,</b> Crescentic glomerulonephritis. <i>Arrows</i> point to a proliferation of parietal epithelial cells in Bowman's capsule, occupying approximately 50% of the entire urinary space. The cells encase and compress the glomerular tuft. <b>I,</b> Diffuse membranous glomerulopathy. The H&E (hematoxylin and eosin)-stained biopsy shows glomerular basement membranes that are uniformly</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f008.jpg" class="SCImage"><div> Acute tubular necrosis. Coagulation necrosis of proximal renal tubule cells (<i>arrows</i>) is evident with some detachment from the basement membrane. This will form renal tubular cell casts. <i>(From Kern WF, Silva FG, Laszik ZG, et al [eds]: Atlas of Renal Pathology. Philadelphia, WB Saunders, 1999, p 129, Fig. 12-3.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-019-f009.jpg" class="SCImage"><div> Acute pyelonephritis showing a neutrophil-dominant infiltrate in the tubular lumens (<i>arrow</i>) and interstitium. The neutrophils in the lumens are molded into white blood cell (WBC) casts, which are passed in the urine along with free neutrophils and bacteria (pyuria). <i>(From Kern WF, Silva FG, Laszik ZG, et al [eds]: Atlas of Renal Pathology. Philadelphia, WB Saunders, 1999, p 149, Fig. 13-15B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f001.jpg" class="SCImage"><div> Signs of acute inflammation. The patient has erysipelas of the face due to group A streptococcus. Signs of acute inflammation that are present in the photograph include redness (rubor) and swelling (tumor). The infection is associated with warm skin (calor) and pain (dolor). <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 37, Fig. 1-106.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f010.jpg" class="SCImage"><div> Cell cycle. Refer to the description in the text. <i>(From Burns ER, Cave MD: Rapid Review: Histology and Cell Biology. St. Louis, Mosby, 2004, p 36, Fig. 3-5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f011.jpg" class="SCImage"><div> Ehlers-Danlos syndrome. The patient shows extreme hyperelasticity of the skin. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 150, Fig. 3-112.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f012.jpg" class="SCImage"><div> Keloid formation. The patient shows a raised, thickened scar over the dorsum of the hand. <i>(From Lookingbill D, Marks J: Principles of Dermatology, 3rd ed. Philadelphia, WB Saunders, 2000, p 115, Fig. 8-5A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f013.jpg" class="SCImage"><div> Absolute leukocytosis with left shift. Arrows point to band (stab) neutrophils, which exhibit prominence of the azurophilic granules (toxic granulation). Vacuoles in the cytoplasm represent phagolysosomes. <i>(From Hoffbrand AV: Color Atlas: Clinical Hematology, 3rd ed. St. Louis, Mosby, 2000, p 115, Fig. 7-11A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f014.jpg" class="SCImage"><div> <b>A,</b> Macrophage. Note the phagocytic debris in the cytosol. <b>B,</b> Lymphocyte. Note the large nucleus and scant cytoplasm. <b>C,</b> Plasma cell. Note the extensive rough endoplasmic reticulum and globules of immunoglobulin in the cytosol. <b>D,</b> Eosinophil. Note the crystalline material in the cytosol that becomes Charcot-Leyden crystals in sputum of asthmatics. <i>(<b>A, B, C, D</b> courtesy of William Meek, Ph.D., Professor and Vice Chairman of Anatomy and Cell Biology, Oklahoma State University, Center for Health Sciences, Tulsa, Oklahoma.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f015.jpg" class="SCImage"><div> Rouleaux formation. The arrows show red blood cells stacked like coins. <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders/Elsevier, 2008, p 1175, Fig. 161-19.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f016.jpg" class="SCImage"><div> Serum protein electrophoresis in acute inflammation (<b>A</b>) and chronic inflammation (<b>B</b>). Refer to the text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f002.jpg" class="SCImage"><div> Neutrophil events in acute inflammation. See text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f003.jpg" class="SCImage"><div> Acute inflammation. Histologic section of lung in bronchopneumonia showing sheets of neutrophils with multilobed nuclei. <i>(From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 182, Fig. 8-8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f004.jpg" class="SCImage"><div> Oxygen-dependent myeloperoxidase system. A series of biochemical reactions occurs in the phagolysosome, resulting in the production of hypochlorous free radicals (bleach; HOCl<sup>•</sup>) that destroy bacteria. Fe<sup>2+</sup>, reduced iron; GSH, reduced glutathione; G6-P, glucose 6-phosphate; GSSG, oxidized glutathione; H<sub>2</sub>O<sub>2</sub>, peroxide; MPO, myeloperoxidase; NADP, oxidized form of nicotinamide adenine dinucleotide phosphate; NADPH, reduced nicotinamide adenine dinucleotide phosphate; OH<sup>•</sup>, hydroxyl free radical; 6PG, 6-phosphogluconate; SOD, superoxide dismutase.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f005.jpg" class="SCImage"><div> Arachidonic acid metabolism. Arachidonic acid is released from membrane phospholipids. It is converted into prostaglandins (PGs), thromboxane A<sub>2</sub> (TXA<sub>2</sub>), and leukotrienes (LTs). See text for further discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f006.jpg" class="SCImage"><div> Purulent (suppurative) inflammation. The photograph shows a skin abscess (furuncle) due to <i>Staphylococcus aureus</i>. Abscesses are pus-filled nodules located in the dermis. Note the multiple draining sinus tracts filled with pus. <i>(From Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 33, Fig. 66.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f007.jpg" class="SCImage"><div> Fibrinous inflammation. The surface of the heart is covered by a shaggy, fibrinous exudate. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 25, Fig. 1-59.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f008.jpg" class="SCImage"><div> Pseudomembranous inflammation. There is necrosis and a yellow exudate covering the mucosal surface of the colon due to a toxin produced by <i>Clostridium difficile</i>. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 202, Fig. 26-10.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-002-f009.jpg" class="SCImage"><div> Chronic inflammation. This tissue shows an infiltrate of predominantly lymphocytes and plasma cells (cells with eccentric nucleus and perinuclear clearing). <i>(From Gitlin M, Strauss R: Atlas of Clinical Hepatology. Philadelphia, WB Saunders, 1995, p 59, Fig. 5-11.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-020-f001.jpg" class="SCImage"><div> Exstrophy of the bladder. Red mucosa of the urinary bladder is seen protruding through the defect in the anterior abdominal wall. <i>(Courtesy of Dr. Roger D. Smith, Cincinnati, Ohio, and GRIPE.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-020-f002.jpg" class="SCImage"><div> Gram stain of <i>Escherichia coli</i>: Note the gram-negative rods. <i>(From McPherson R, Pincus M: Henry's Clinical Diagnosis and Management by Laboratory Methods, 21st ed. Philadelphia, Saunders, 2006, Fig. 56-14.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-020-f003.jpg" class="SCImage"><div> Transitional cell carcinoma of urinary bladder. The <i>arrow</i> shows a papillary exophytic mass arising from the mucosal surface of the bladder. The red lesion in the prostate gland is an infarction. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1328, Fig. 17-175.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-020-f004.jpg" class="SCImage"><div> Hypospadias. The <i>arrow</i> shows the urethral opening on the ventral surface of the penis. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 211, Fig. 11-6.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-020-f005.jpg" class="SCImage"><div> Varicocele in the left scrotal sac. Note the "bag of worms" appearance. See text for the discussion. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 545, Fig. 18-27.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-020-f006.jpg" class="SCImage"><div> Seminoma of the testicle showing the scrotal mass (<b>A</b>) and the excised mass (<b>B</b>). Note the tumor replaces most of the testicle. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 307, Fig. 38-8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-020-f007.jpg" class="SCImage"><div> Microscopic section of a seminoma. Note the large tumor cells with fibrous septa infiltrated by numerous lymphocytes. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1421, Fig. 18-57.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-020-f008.jpg" class="SCImage"><div> Benign prostatic hyperplasia. The gross section of prostate shows yellow periurethral nodular masses, causing narrowing of the lumen of the urethra. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 249, Fig. 12-31.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-020-f009.jpg" class="SCImage"><div> Prostate cancer. The <i>arrow</i> points to a triangular area of prostate cancer located at the periphery of the gland. The remainder of the gland has a normal, spongy appearance. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1052, Fig. 21-34.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f001.jpg" class="SCImage"><div> Genital infections. <b>A,</b> <i>Candida</i>. <i>Bottom arrow</i> shows elongated yeasts (pseudohyphae), <i>top arrow</i> shows yeasts. <b>B,</b> <i>Gardnerella vaginalis</i>. Superficial squamous cells are covered by granular material representing bacterial organisms attached to the surface. <b>C,</b> Herpes type 2. <i>Arrows</i> show ulcerated, red lesions on the shaft of the penis. <b>D,</b> Herpes type 2. Biopsy showing a multinucleated squamous cell with smudged, "ground glass" nuclei with intranuclear inclusions (<i>arrow</i>). <b>E,</b> Human papillomavirus. Numerous keratotic papillary processes are present on the surface of the labia. These are called venereal warts or condylomata acuminata. <b>F,</b> <i>Neisseria gonorrhoeae</i>. Neutrophils (<i>arrow</i>) show numerous, phagocytosed gram-negative diplococci. <b>G,</b> <i>Treponema pallidum</i>. Note the well-demarcated primary chancre just distal to the glans penis. <b>H,</b> <i>Treponema pallidum</i>. Note the characteristic palmar papules and plaques of secondary syphilis. <b>I</b>, <i>Treponema pallidum</i>. Note the flat, plaque-like lesions (<i>arrows</i>) of condyloma latum. <b>J,</b> <i>Trichomonas vaginalis</i>. Note the numerous pear-shaped, flagellated organisms (<i>arrows</i>). <i>(<b>A</b> and <b>D</b> from Atkinson BF: Atlas of Diagnostic Cytopathology. Philadelphia, WB Saunders, 1992, pp 76, 78, and 80, Figs. 2-49B, 2-55, and 2-63, respectively; <b>B</b> and <b>E</b> from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, pp 261 and 260, Figs. 13-10B and 13-8, respectively; <b>C</b> from Bouloux P-M: Self-Assessment Picture Tests: Medicine, Vol 1. St. Louis, Mosby, 1996, p 17, Fig. 33; <b>F</b> from Greer I, Cameron IT, Kitchener HC, Prentice A: Mosby's Color Atlas and Text of Obstetrics and Gynecology. St. Louis, Mosby, 2000, p 274, Fig. 10-50; <b>G</b> from Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 537, Fig.</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f010.jpg" class="SCImage"><div> Menstrual cycle. See text for discussion. FSH, follicle-stimulating hormone; LH, luteinizing hormone. <i>(From Brown TA: Rapid Review Physiology. St. Louis, Mosby, 2007, p 99, Fig. 3-15.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f011.jpg" class="SCImage"><div> Subnuclear vacuoles (<i>arrows</i>) containing mucin push the nuclei of the endometrial cells toward the apex of the cell. Eventually the mucin passes the nucleus and enters the lumen marking the beginning of the secretory phase. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1081, Fig. 21-5B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f012.jpg" class="SCImage"><div> Schematic of sex hormone-binding globulin (SHBG). See text for discussion. FT, free testosterone. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 366, Fig. 10-11.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f013.jpg" class="SCImage"><div> Hirsutism. <b>A,</b> This woman has excess hair above the lip and on the chin. <b>B,</b> A woman with a male distribution of hair from the mons pubis to the umbilicus. <i>(<b>A</b> from Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 369, Fig. 10-12; <b>B</b> from Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 47, Fig. 93.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f014.jpg" class="SCImage"><div> Clitoromegaly. Note the elongation of the clitoris, which is the gold standard sign of virilization. <i>(From Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 4, Fig. 7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f015.jpg" class="SCImage"><div> Polycystic ovary syndrome showing an enlarged ovary with multiple subcortical cysts. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 262, Fig. 13-17A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f016.jpg" class="SCImage"><div> Polycystic ovary syndrome showing an ultrasound with an enlarged ovary demonstrating multiple subcortical cysts (<i>arrows</i>). <i>(From Pretorius ES, Solomon JA: Radiology Secrets, 2nd ed. St. Louis, Mosby, 2006, p 204, Fig. 24-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f017.jpg" class="SCImage"><div> Adenomyosis. The <i>solid arrow</i> shows an area of hemorrhage surrounded by irregularly thickened endometrial stroma. The <i>interrupted arrow</i> shows a nabothian cyst in the endocervical canal. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1578, Fig. 19-123.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f018.jpg" class="SCImage"><div> Endometriosis implants on a loop of intestine. Note the serosal surface has multiple areas of hemorrhage with a "powder burn" appearance. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 126, Fig. 7-17.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f019.jpg" class="SCImage"><div> Endometrial polyp. Note hemorrhagic polyp arising from the endometrial mucosa. It is a common cause of uterine bleeding. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1082, Fig. 22-27C.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f002.jpg" class="SCImage"><div> Lichen sclerosis. The vulva shows a parchment-like appearance (<i>arrow</i>). <i>(From Savin JAA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, p 124, Fig. 4.81.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f020.jpg" class="SCImage"><div> Simple hyperplasia of endometrial glands showing cystic dilation and focal areas of glandular outpouching. There is no gland crowding or stratification of the epithelial lining. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1086, Fig. 22-31A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f021.jpg" class="SCImage"><div> Endometrial carcinoma showing necrotic tumor filling the uterine cavity and extending completely through the uterine wall and into the endocervical canal. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1586, Fig. 19-136B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f022.jpg" class="SCImage"><div> Leiomyomas. In sagittal section, multiple well-circumscribed, gray-white nodules (leiomyomas) are dispersed throughout the myometrium. Submucosal leiomyomas are a common cause of uterine bleeding. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 271, Fig. 13-49.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f023.jpg" class="SCImage"><div> Pelvic inflammatory disease. Note the pus filling the lumen of the fallopian tube. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1638, Fig. 19-192B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f024.jpg" class="SCImage"><div> Ruptured ectopic tubal pregnancy showing marked hemorrhage (hematosalpinx) and an embryo (<i>arrow</i>) in the center of the clot material. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1639, Fig. 19-198.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f025.jpg" class="SCImage"><div> Schematic showing the derivation of primary ovarian tumors. <i>(From Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 729, Fig. 19-16.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f026.jpg" class="SCImage"><div> Normal placenta, showing the fetal side (<b>A</b>) and the maternal side (<b>B</b>). See text for discussion. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 326, Fig. 13-108.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f027.jpg" class="SCImage"><div> Chorionic villi. The outer layer of the villus is covered by two layers of cells called the trophoblast (<i>arrowheads</i>). The outer layer of the trophoblast is lined by syncytiotrophoblast, while the inner layer is lined by cytotrophoblast. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 326, Fig. 13-109.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f028.jpg" class="SCImage"><div> Schematic of placenta praevia. Note how the placenta is implanted over the cervical os. <i>(From Greer I, Cameron IT, Kitchener HC, Prentice A: Mosby's Color Atlas and Text of Obstetrics and Gynecology. St. Louis, Mosby, 2000, p 184, Fig. 7-28.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f029.jpg" class="SCImage"><div> Abruptio placentae. Note the retroplacental blood clot that separated the placenta from its implantation site. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 327, Fig. 13-112.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f003.jpg" class="SCImage"><div> Extramammary Paget's disease. Large, pink-staining, malignant Paget's cells (<i>arrows</i>) are disposed singly and in clusters within the epidermis. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1492, Fig. 19-17B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f030.jpg" class="SCImage"><div> Twin placentas. See text for description. <i>(Redrawn from Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998, Fig. 18-2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f031.jpg" class="SCImage"><div> Complete hydatidiform mole. The enlarged and edematous villi are interconnected by thin cord-like structures. No fetus is present. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 290, Fig. 13-111A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f032.jpg" class="SCImage"><div> Ultrasound of a complete hydatidiform mole showing the classic "snowstorm" appearance. No fetus is present. <i>(From Greer I, Cameron IT, Kitchener HC, Prentice A: Mosby's Color Atlas and Text of Obstetrics and Gynecology. St. Louis, Mosby, 2000, p 94, Fig. 4-22.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f033.jpg" class="SCImage"><div> Locations for breast lesions. See text for discussion. <i>(Redrawn from Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998, Fig. 18-3.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f034.jpg" class="SCImage"><div> Galactorrhea in a patient with a prolactinoma. <i>(From Mansel R, Bundred N: Color Atlas of Breast Disease. St. Louis, Mosby, 1995.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f035.jpg" class="SCImage"><div> Fibrocystic change. The microscopic section shows cystic spaces surrounded by a dense fibrous stroma. The large cyst at the top has eosinophilic staining cells exhibiting apocrine metaplasia. The smaller cysts (<i>arrows</i>) show extensive ductal hyperplasia with a sieve-like pattern. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1780, Fig. 20-30.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f036.jpg" class="SCImage"><div> Fibroadenoma. Note the bulging gray-white surface of this benign stromal tumor. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p. 298, Fig. 14-3.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f037.jpg" class="SCImage"><div> Fibroadenoma: A microscopic section shows compressed, elongated ducts surrounded by neoplastic stromal tissue. <i>(From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 405, Fig. 16-5B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f038.jpg" class="SCImage"><div> Mammogram with microcalcifications. The biopsy in this patient shows breast cancer. <i>(From Pretorius ES, Solomon JA: Radiology Secrets, 2nd ed. St. Louis, Mosby, 2006, p 43, Fig. 6-5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f039.jpg" class="SCImage"><div> <b>A</b>, Ductal carcinoma in situ (DCIS) showing dilated ducts lined by layers of neoplastic cells. Central areas of necrosis (comedo pattern) are present, some of which contain microcalcifications (<i>arrow</i>). <b>B</b>, Lobular carcinoma in situ showing complete replacement and expansion of a lobule by a monomorphic population of cells. <b>C</b>, Infiltrating ductal carcinoma showing a stellate-shaped scar (<i>arrow</i>) in the fat tissue of the breast. <b>D</b>, Mammogram showing a large irregular spicular mass lesion, which on biopsy showed an infiltrating ductal carcinoma. <b>E,</b> Paget's disease of the breast showing an erythematous rash around the nipple. <b>F</b>, Inflammatory carcinoma of the right breast. Note the dimpled appearance of the breast (peau d'orange) and retraction of the skin. <i>(<b>A</b> and <b>B</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, pp 1139, 1142, Figs. 23-16B, 23-20, respectively; <b>C</b> from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 304, Fig. 14-14A; <b>D</b> and <b>F</b> from Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 33, Figs. 6-22, 6-23, respectively; <b>E</b> from Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 468, Fig. 16-13.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f004.jpg" class="SCImage"><div> Embryonal rhabdomyosarcoma of vagina. Note the bloody, necrotic mass protruding out of the vagina. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 266, Fig. 13-29.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f005.jpg" class="SCImage"><div> Clear cell carcinoma of the vagina. Note the clear, vacuolated cells with ill-defined glandular spaces. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 295, Fig. 13-12.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f006.jpg" class="SCImage"><div> Koilocytosis caused by human papillomavirus. The squamous cells have wrinkled pyknotic nuclei surrounded by a clear halo. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 1530, Fig. 19-74.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f007.jpg" class="SCImage"><div> Squamous cell carcinoma of the cervix. Note the bleeding and ulceration in the cervical os. <i>(Courtesy of Dr. Hector Rodriguez-Martinez, Mexico City.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f008.jpg" class="SCImage"><div> Squamous cell carcinoma of cervix with extension down into the vagina, wall of the urinary bladder (<i>solid arrow</i>) and wall of the rectum (<i>interrupted arrow</i>). <i>(Courtesy of Dr. Hector Rodriguez-Martinez, Mexico City.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-021-f009.jpg" class="SCImage"><div> Synthesis of sex hormones in the ovaries. Luteinizing hormone is responsible for stimulation of hormone synthesis in the theca interna surrounding the developing follicle. Follicle-stimulating hormone increases the synthesis of aromatase in granulosa cells. Aromatase converts testosterone to estradiol. <i>(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998, Fig. 18-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f001.jpg" class="SCImage"><div> Pituitary adenoma. The <i>interrupted arrow</i> shows a well-circumscribed mass that has almost completely replaced the pituitary gland. A thin rim of sella turcica is present at the base of the tumor. The <i>solid arrow</i> shows the optic nerve and its proximity to the sella turcica. <i>(From Burger PC, Scheithauer BW, Vogel KS: Surgical Pathology of the Nervous System, 4th ed. London, Churchill Livingstone, 2002, p 444, Fig. 9-20.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f010.jpg" class="SCImage"><div> Severe exophthalmos in Graves' disease. Note the proptosis of the eye, increased vascularity of the conjunctiva, and the enlarged lacrimal gland. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 232, Fig. 10-35.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f011.jpg" class="SCImage"><div> Pretibial myxedema in Graves' disease. Note the thickened area of erythema involving the pretibial area and dorsum of the foot. <i>(Courtesy of R.A. Marsden, MD, St. George's Hospital, Lodon.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f012.jpg" class="SCImage"><div> Patient with a multinodular goiter. Note the diffuse enlargement of the lower anterior neck. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 199, Fig. 9-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f013.jpg" class="SCImage"><div> Gross of multinodular goiter. Note the diffusely enlarged gland with numerous cystic nodules filled with excess colloid. Hemorrhage has occurred into many of the cysts. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 268, Fig. 33-3.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f014.jpg" class="SCImage"><div> Papillary carcinoma of thyroid showing branching papillae and blue concretions (<i>arrows</i>) representing psammoma bodies. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 534, Fig. 9-37A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f015.jpg" class="SCImage"><div> Total serum calcium in a normal individual (<b>A</b>), individual with hypoalbuminemia (<b>B</b>), and individual with alkalosis (<b>C</b>). Refer to the text for discussion. PTH, parathyroid hormone.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f016.jpg" class="SCImage"><div> Pseudohypoparathyroidism. Note the short fourth and fifth digits, producing the classic "knuckle-knuckle-dimple-dimple" sign. <i>(From Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 3. London, Mosby-Wolfe, 1997, p 14, Fig. 27.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f017.jpg" class="SCImage"><div> Parathyroid adenoma in primary hyperparathyroidism. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 597, Fig. 10-2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f018.jpg" class="SCImage"><div> Hand in primary hyperparathyroidism. The radiograph shows a concavity at the radial aspect of the middle phalanges of the index and middle fingers (<i>arrows</i>). <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 309, Fig. 3.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f019.jpg" class="SCImage"><div> Schematic showing serum calcium and serum PTH in different disorders. The center square with the shaded areas represent the normal serum calcium and PTH. Area A describes primary hypoparathyroidism (↓ serum calcium, ↓ serum PTH); area B represents hypoalbuminemia (↓ serum calcium, normal serum PTH); area C represents secondary hyperparathyroidism (↓ serum calcium, ↑ serum PTH); D represents respiratory alkalosis (normal serum calcium, serum PTH); E represents primary hyperparathyroidism (↑ serum calcium, ↑ serum PTH); and F represents hypercalcemia associated with malignancy (↑ serum calcium, ↓ serum PTH). PTH, parathyroid hormone.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f002.jpg" class="SCImage"><div> Schematic of the metyrapone test: a normal response (<b>A</b>) and the response expected in hypopituitarism (<b>B</b>). See text for discussion. ACTH, adrenocorticotropic hormone.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f020.jpg" class="SCImage"><div> Adrenocortical hormone synthesis. The zona glomerulosa produces mineralocorticoids (e.g., aldosterone), the zona fasciculata produces glucocorticoids (e.g., cortisol), and the zona reticularis produces sex hormones (e.g., testosterone). The 17-hydroxycorticoids (17-OH) are 11-deoxycortisol and cortisol. The 17-ketosteroids (17-KS, weak androgens) are dehydroepiandrosterone and androstenedione. Testosterone is converted to dihydrotestosterone (DHT) by 5α-reductase in extra-adrenal tissue.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f021.jpg" class="SCImage"><div> Addison's disease. Note the increased melanin pigmentation of the buccal mucosa. <i>(From Savin JAA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, p 1105, Fig. 4.44.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f022.jpg" class="SCImage"><div> Schematic of the metyrapone test in Addison's disease. Metyrapone blocks 11-hydroxylase in the adrenal gland. This further decreases cortisol leading to a marked increase in adrenocorticotropic hormone (ACTH) due to a loss of negative feedback. However, the increase in ACTH does <i>not</i> increase the synthesis of 11-deoxycortisol in the adrenal cortex, which is destroyed in Addison's disease.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f023.jpg" class="SCImage"><div> Newborn girl with ambiguous genitalia. Note the enlarged clitoris and the partially fused labia majora suggesting the presence of a scrotum. <i>(Courtesy of Patrick C. Walsh, MD, Johns Hopkins School of Medicine.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f024.jpg" class="SCImage"><div> Patient with Cushing syndrome, showing "moon facies," truncal obesity, and purple abdominal striae. <i>(From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 426.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f025.jpg" class="SCImage"><div> Schematic of catecholamine synthesis and degradation. Note the role of tyrosine in the synthesis of catecholamines. Catecholamines are important neurotransmitters and are involved in cardiac contraction, vasoconstriction, and gastrointestinal motility. BH<sub>2</sub>, dihydrobiopterin; BH<sub>4</sub>, tetrahydrobiopterin; COMT, catechol-<i>O</i>-methyltransferase; HVA, homovanillic acid; MAO, monoamine oxidase; VMA, vanillylmandelic acid. <i>(From Pelley J, Goljan E: Rapid Review Biochemistry, 2nd ed. St. Louis, Mosby, 2007, p 144, Fig. 8-6.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f026.jpg" class="SCImage"><div> Neuropathic pressure ulcers. Note the areas of ulcerations over the pressure points on the plantar surfaces of both feet. The patient had no sensation for pain in these areas due to a peripheral neuropathy. This emphasizes the importance for checking pain sensation of the feet in all diabetic patients. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 641, Fig. 20-72.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f027.jpg" class="SCImage"><div> Diabetic retinopathy. The retina shows tiny dots representing retinal hemorrhages from ruptured microaneurysms and retinal exudates (sharply defined white areas). <i>(From Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 2858, Fig. 449-15.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f028.jpg" class="SCImage"><div> Metabolic changes in diabetic ketoacidosis (DKA). Refer to the text for discussion. VLDL, very low-density lipoprotein. <i>(From Pelley J, Goljan EF: Rapid Review: Biochemistry. St. Louis, Mosby, 2004, p 176, Fig. 9-5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f003.jpg" class="SCImage"><div> Acromegaly showing the patient before development of the tumor (<i>left</i>) and after development of the tumor (<i>right</i>). Note the coarse facial features and enlargement of the jaw and lips. <i>(From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 407.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f004.jpg" class="SCImage"><div> Schematic of total serum thyroxine (T<sub>4</sub>) in a normal individual (<b>A</b>) and an individual with an increase in thyroid-binding globulin (TBG) (<b>B</b>). The actual numbers do not represent the true concentration of T<sub>4</sub> and free T<sub>4</sub> (FT<sub>4</sub>). The bars represent TBG and the circles are T<sub>4</sub> bound to TBG and T<sub>4</sub> that is free (FT<sub>4</sub>). FT<sub>4</sub> normally has a negative feedback with thyroid-stimulating hormone (TSH). Refer to the text for a complete discussion. <i>(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998, Fig. 19-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f005.jpg" class="SCImage"><div> Nuclear scan of thyroid showing "cold" nodules (lack of uptake or radioactive iodine) in both lobes of the thyroid (<i>arrows</i>). <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 531, Fig. 2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f006.jpg" class="SCImage"><div> Patient with a midline thyroglossal duct cyst. <i>(From Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 52, Fig. 103.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f007.jpg" class="SCImage"><div> Microscopic section of Hashimoto's thyroiditis. Note the prominent germinal follicle and heavy infiltrate of lymphocytes throughout the gland with destruction of the thyroid follicles. <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 522, Fig. 9-10.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f008.jpg" class="SCImage"><div> Primary hypothyroidism in a patient with Hashimoto's thyroiditis. The patient has a puffy face, particularly around the eyes, and coarse hair. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 325, Fig. 7-72.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-022-f009.jpg" class="SCImage"><div> Graves' disease. The patient has exophthalmos and a diffuse enlargement of the thyroid gland (goiter). <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 323, Fig. 7-61.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f001.jpg" class="SCImage"><div> Osteogenesis imperfecta. Note the faint blue tint of the sclera representing the reflection of the underlying choroidal veins. <i>(From Mir MA: Atlas of Clinical Diagnosis. London, Saunders, 1995.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f010.jpg" class="SCImage"><div> Osteoarthritis. Both the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints in both hands show protuberances along their lateral margins representing osteophyte formation in the joints. The DIP protuberances are called Heberden's nodes and the PIP protuberances are called Bouchard's nodes. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 636, Fig. 20-59.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f011.jpg" class="SCImage"><div> Schematic of rheumatoid arthritis in a joint. See text for description. <i>(From Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 820, Fig. 7-18 on the left.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f012.jpg" class="SCImage"><div> Patient with rheumatoid arthritis showing bilateral ulnar deviation of the hands and prominent swelling of the second and third metacarpophalangeal joints. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 121, Fig. 3-3.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f013.jpg" class="SCImage"><div> Acute gouty arthritis involving the left big toe. Note the erythema and swelling of the joint. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 634, Fig. 20-55.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f014.jpg" class="SCImage"><div> Tophi involving the soft tissue around the joints in both hands. The white material represents crystals of monosodium urate. <i>(From Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 55, Fig. 109.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f015.jpg" class="SCImage"><div> Chondrocalcinosis (pseudogout). The radiograph shows linear calcifications in the fibrocartilage in the knee joint (<i>arrow</i>) in a patient with the osteoarthritis variant of calcium pyrophosphate deposition. <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 278, Fig. 10.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f016.jpg" class="SCImage"><div> Man with ankylosing spondylitis. The patient cannot bend forward owing to fusion of the vertebra. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, Fig. 3-48.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f017.jpg" class="SCImage"><div> Radiograph showing fused vertebra ("bamboo" spine) in ankylosing spondylitis. <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 277, Fig. 7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f018.jpg" class="SCImage"><div> Radiograph of the hand in psoriatic arthritis. The distal interphalangeal joint of the middle finger shows the classic "pencil-in-cup" deformity (<i>arrows</i>). The metallic foreign body in the soft tissue was an incidental finding. <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 276, Fig. 6.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f019.jpg" class="SCImage"><div> Erythema chronicum migrans in a patient with Lyme disease. Raised central area is the site of the tick bite. Concentric area of erythema surrounds the bite site. <i>(From Lookingbill D, Marks J: Principles of Dermatology, 3rd ed. Philadelphia, WB Saunders, 2000, p 269, Fig. 17-5A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f002.jpg" class="SCImage"><div> Chronic osteomyelitis. The <i>solid arrow</i> points to necrotic bone in the center of a draining abscess (sequestrum). The <i>interrupted arrow</i> is a rim of new bone formation (involucrum). <i>(From Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 810, Fig. 21-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f020.jpg" class="SCImage"><div> Duchenne's muscular dystrophy (DMD). <b>A,</b> Pseudohypertrophy of the calf. <b>B,</b> A child with DMD performing the Gower's maneuver. <i>(From Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, p 269, Figs. 14-10 and 14-12.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f021.jpg" class="SCImage"><div> Myotonic dystrophy. The patient shows frontal balding, drooping of the eyelids, sagging of the facial muscles, and atrophy of the sternocleidomastoid muscles. <i>(From Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, p 272, Fig. 14-16.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f022.jpg" class="SCImage"><div> Patient with myasthenia gravis showing ptosis of the left eye (<b>A</b>) followed by opening of the eye (<b>B</b>) after intravenous injection of Tensilon. <i>(From Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, p 263, Fig. 14-5A and B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f023.jpg" class="SCImage"><div> Dupuytren's contractures in the hand. The <i>arrows</i> show thickening of the palmar fascia producing cords that cause the fingers to have a hook-like deformity. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 40, Fig. 7-4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f024.jpg" class="SCImage"><div> <b>A,</b> Radiograph showing a Colles fracture. Note the fracture lines (<i>arrows</i>) in the distal radius and the styloid process of the ulna. <b>B,</b> Ganglion cyst on the dorsum of the wrist. <b>C,</b> Magnetic resonance image of a normal knee joint and its structures. <b>D,</b> Patient with scoliosis. The patient has lateral curvature of the spine with increased convexity to the right. There is obvious scapular asymmetry in the upright position. <i>(<b>A</b> from Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 440, Fig. 9; <b>B</b> from Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 171, Fig. 8-74; <b>C</b> from Moore NA, Roy WA: Rapid Review Gross and Developmental Anatomy, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 148, Fig. 5-6; <b>D</b> from Zitelli B: Atlas of Pediatric Physical Diagnosis, 3rd ed. St. Louis, Mosby, 1997.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f003.jpg" class="SCImage"><div> Osteoporosis of vertebral column. The vertebral body on the right shows decreased bone mass caused by compression fractures when compared with a normal vertebral body on the left. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1284, Fig. 26-12.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f004.jpg" class="SCImage"><div> Elderly woman with osteoporosis showing the classic Dowager's hump. <i>(From Seidel HM, Ball JW, Danis JE, Benedict GW: Mosby's Guide to Physical Examination, 6th ed. St. Louis, Mosby Elsevier, 2006, p 756, Fig. 21-78.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f005.jpg" class="SCImage"><div> Schematic showing a pertrochanteric fracture (<b>A</b>) and a subcapital fracture (<b>B</b>). See text for discussion. <i>(From Moore NA, Roy WA: Rapid Review Gross and Developmental Anatomy, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 147, Fig. 5-4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f006.jpg" class="SCImage"><div> Radiograph showing avascular necrosis of the femoral head. The <i>interrupted circle</i> highlights an area of increased bone density within which is a fracture site (<i>arrow</i>). <i>(From Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 2144, Fig. 24-8A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f007.jpg" class="SCImage"><div> Radiograph of the humerus in Paget's disease. Note the cortical thickening of the bone and the ragged appearing lytic areas throughout the bone matrix. <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 311, Fig. 1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f008.jpg" class="SCImage"><div> Synovial fluid with special polarization. Special red filter causes the background to be red. Crystals are aligned parallel to the slow ray (axis) of the compensator (<i>arrow</i>). If the crystal is yellow when parallel to the slow ray, as in this figure, the crystal demonstrates negative birefringence. If the crystal is blue when parallel to the slow ray, the crystal demonstrates positive birefringence. <i>(From Henry JB: Clinical Diagnosis and Management by Laboratory Methods, 20th ed. Philadelphia, WB Saunders, 2001, Plate 19-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-023-f009.jpg" class="SCImage"><div> Schematic of osteoarthritis in a joint. See text for description. <i>(From Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 820, Fig. 7-18 on the right.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-024-f001.jpg" class="SCImage"><div> Viral infections. <b>A,</b> Verruca vulgaris (common wart) on the fingers, showing scaling, verrucous papules with interrupted skin lines. <b>B,</b> Molluscum contagiosum, showing small bowl-shaped lesions with central areas of depression (umbilication). <b>C,</b> Rubeola (regular measles). Note the Koplik spots on the buccal mucosa. <b>D,</b> Rubeola. A macular rash begins on the face and neck and then becomes maculopapular (this patient) and spreads to the trunk and extremities in irregular confluent patches. <b>E,</b> Rubella. Note the red Forchheimer spots on the soft and hard palate. <b>F,</b> Rubella. Note the fine pinkish red maculopapular rash. The lesions remain discrete and do not become confluent as they do in rubeola. <b>G,</b> Erythema infectiosum. Note the "slapped face" appearance. <b>H,</b> Roseola infantum. Note the maculopapular rash, which normally blanches with pressure. There are subtle peripheral halos due to vasoconstriction around some of the lesions. <b>I,</b> Varicella. Note the vesicles and pustules surrounded by an erythematous base. The lesions are at different stages of development. <b>J,</b> Herpes zoster (shingles). Note the erythematous vesicular rash with the characteristic "band" distribution, which starts from the midline and extends to the lateral trunk. <i>(<b>A</b> from Lookingbill D, Marks J: Principles of Dermatology, 3rd ed. Philadelphia, WB Saunders, 2000, p 68, Fig. 6-1A; <b>B</b> and <b>G</b> from Savin JA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, pp 79 and 6, Figs. 2-47 and 1-10, respectively; <b>C</b> from Centers for Disease Control and Prevention Web site-Public Health Image Library. Image #4500. Available at <a href="http://phil.cdc.gov/phil/details.asp" target="_blank">http://phil.cdc.gov/phil/details.asp</a>; <b>D</b> from Zitelli B: Atlas of Pediatric Physical Diagnosis, 3rd ed. St. Louis, Mosby, 1997; <b>E</b> from Eisen D, Lynch DP: The </i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-024-f010.jpg" class="SCImage"><div> <b>A,</b> Alopecia areata. Note the area of baldness and the short hairs that have the appearance of exclamation marks. <b>B,</b> Nail anatomy. See text for discussion. <b>C,</b> Mees bands. Note the transverse white lines in the nail plate that extend proximally until they are pared off. <b>D,</b> Beau's lines. Note the transverse grooves or depressions that are oriented parallel to the lunula. <i>(<b>A</b> from Savin JA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, p 96, Fig. 4.5; <b>B</b> and <b>C</b> from Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, pp 140 and 146, Figs. 8-3 and 8-7, respectively; <b>D</b> from Callen JP, Paller AS, Greer KE, Swinyer LJ: Color Atlas of Dermatology, 2nd ed. Philadelphia, WB Saunders, 2000.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-024-f002.jpg" class="SCImage"><div> Bacterial infections. <b>A,</b> Gram stain of <i>Staphylococcus aureus</i>. Note the gram-positive cocci, some of which are forming clusters. <b>B,</b> Impetigo of the face showing "honey-colored" crusts overlying an erythematous base. <b>C,</b> Gram stain of <i>Streptococcus pyogenes</i>. Note the gram-positive cocci in chains. <b>D,</b> Tuberculoid leprosy. Note the hypopigmented macule, an early finding in tuberculoid leprosy. <b>E,</b> Lepromatous leprosy. Note the nodular lesions on the face giving the patient a leonine facies. <b>F,</b> Acne vulgaris. Note the severe facial acne with inflamed papules and cystic lesions. <i>(<b>A</b> from McPherson R, Pincus M: Henry's Clinical Diagnosis and Management by Laboratory Methods, 21st ed. Philadelphia, WB Saunders, 2007, p 1018, Fig. 56-2; <b>B</b> from Lookingbill D, Marks J: Principles of Dermatology, 3rd ed. Philadelphia, WB Saunders, 2000, pp 217 and 213, Figs. 13-9 and 13-4A, respectively; <b>C</b> from Murray PR, Shea YR: Medical Microbiology, 2nd ed. St. Louis, Mosby, 2002, p 238, Fig. 23-1; <b>D</b> from Cohen J: Infectious Disease, 2nd ed. St. Louis, Mosby, 2003; <b>E</b> and <b>F</b> from Savin JA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, pp 23 and 135, Figs. 1-48 and 5-20, respectively.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-024-f003.jpg" class="SCImage"><div> <b>A,</b> Potassium hydroxide (KOH) preparation of skin scrapings showing hyphae and yeasts. <b>B,</b> Tinea capitis due to <i>Trichophyton tonsurans</i>. Note the area of alopecia (hair loss) with black dots representing broken off hairs and scaling of the skin. <b>C,</b> Tinea corporis showing annular lesions with erythematous margins and clear centers. <b>D,</b> Tinea cruris. Note the scaly, erythematous rash in the groin. <b>E,</b> Tinea versicolor showing skin with pink-tan patches (hyperpigmentation) intermixed with normal skin. The hyperpigmented lesions should be scraped for a KOH preparation. <b>F,</b> <i>Malassezia furfur</i>. Note the classic spaghetti (hyphae) and meatball (yeasts) morphologic appearance. <b>G,</b> Seborrheic dermatitis. Note the erythematous, greasy scaling rash in the nasolabial fold. It is caused by <i>M. furfur</i>. <b>H,</b> Lymphocutaneous sporotrichosis showing a linear array of suppurating subcutaneous nodules. <i>(<b>A</b> and <b>B</b> from Goldstein BG: Practical Dermatology, 2nd ed. St. Louis, Mosby, 1997, pp 24, 97, Fig. 3-2 and Fig. 10-1, respectively; <b>C</b> from Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 97, Fig. 2-57; <b>D</b> and <b>G</b> from Savin JA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, pp 123 and 9, Figs. 4.78 and 1.17, respectively; <b>E</b> from Lookingbill D, Marks J: Principles of Dermatology, 3rd ed. Philadelphia, WB Saunders, 2000, p 227, Fig. 14-2; <b>F</b> from Midgley G, Clayton Y, Hay RJ: Diagnosis in Color: Medical Mycology. London, Mosby-Wolfe, 1997, p 73, Fig. 93; <b>H</b> from Murray PR, Shea YR: Medical Microbiology, 2nd ed. St. Louis, Mosby, 2002, p 163, Fig. 43-14.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-024-f004.jpg" class="SCImage"><div> <b>A,</b> Cutaneous larva migrans. Note irregular, erythematous tracts beneath the skin surface. <b>B,</b> Scabies. Note the erythematous area in the web between the fingers. The <i>arrows</i> show raised burrows. <b>C,</b> <i>Pediculus capitis</i>. Note the white nits (eggs) attached to the hair shafts. <b>D,</b> <i>Pediculus corporis</i>. Note the numerous erythematous papules over the back of this homeless person. <b>E,</b> <i>Phthirus pubis</i>. Note the crab-like appearance of the louse. <i>(<b>A</b> and <b>B</b> courtesy of R.A. Marsden, MD, St. George's Hospital, London; <b>C</b> from Kliegman RM, Jenson HB, Behrman RE, Stanton BF: Nelson's Textbook of Pediatrics, 18th ed. Philadelphia, Saunders Elsevier, 2007, p 2758, Fig. 667-6; <b>D</b> from Savin JA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, p 214, Fig. 9.3; <b>E</b> from Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 399, Fig. 16-90 right.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-024-f005.jpg" class="SCImage"><div> <b>A,</b> Solar lentigo. Note the numerous brown macules on the dorsum of the hand. <b>B,</b> Vitiligo. Note the patchy depigmentation of the skin. <b>C,</b> Melasma. Note the facial hyperpigmentation in this pregnant woman. <b>D,</b> Junctional nevus. Note the oval, uniformally pigmented macular lesion. <b>E,</b> Compound nevus. Note the pigmented lesion with the slightly papillomatous appearing surface. <b>F,</b> Intradermal nevus. Note the raised, pigmented lesion with the papillomatous appearing surface. <b>G,</b> Dysplastic nevus syndrome. Note the numerous pigmented lesions over the back and neck. The inset shows a dysplastic nevus that is >6 mm in diameter and shows variable pigmentation. <b>H,</b> Superficial spreading malignant melanoma. The lesion on the patient's forearm is black, is multinodular, and has an irregular border with areas of pale gray discoloration. <b>I,</b> Lentigo maligna melanoma. Note that the facial lesion shows asymmetry, border irregularity, color variation, and a diameter >6 mm. <b>J,</b> Acral lentiginous malignant melanoma. Note the pigmented lesion under the nail that has spread to involve the proximal nail bed. <b>K,</b> ABCD changes in malignant melanoma. See text for discussion. <i>(<b>A</b> and <b>I</b> from Lookingbill D, Marks J: Principles of Dermatology, 3rd ed. Philadelphia, WB Saunders, 2000, p 94, Figs. 7-2 and 7-4B, respectively; <b>B</b> courtesy of The Honickman Collection of Medical Images in memory of Elaine Garfinkel and The Jefferson Clinical Images Collection [through the generosity of JMB, AKR, LKB and DA]; <b>C, D, E,</b> and <b>F</b> from Habif T: Clinical Dermatology, 4th ed. St. Louis, Mosby, 2004; <b>G</b> from Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 854, Fig. 22-20C; <b>H</b> from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 327, Fig. 15-57A; <b>J</b> from Savin JA, Hunter JAA, Hepbu</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-024-f006.jpg" class="SCImage"><div> <b>A,</b> Seborrheic keratosis. Note the numerous raised, pigmented lesions with a verrucoid surface. These lesions appeared suddenly (Leser-Trélat sign) in this patient indicating a possible underlying gastric adenocarcinoma. In most cases, they are a common lesion in the elderly population where they frequently occur on the face and axilla. <b>B,</b> Acanthosis nigricans. Note the pigmented verrucoid lesion in the axilla. Like the Leser-Trélat sign, these lesions may be associated with an underlying gastric adenocarcinoma or other disorders. <b>C,</b> Keratoacanthoma. Note the crateriform tumor with a central keratin plug. This looks very similar to a basal cell carcinoma; however, it appears rapidly and spontaneously resolves, unlike a basal cell carcinoma. A biopsy settles the issue. <b>D,</b> Epidermoid cyst. Note the dome-shaped lesion near the hairline on the neck. It has two openings on the surface. <b>E,</b> Pilar cyst. Note the dome-shaped swelling on the scalp. <b>F,</b> Fibroepithelial tag. Note the flesh-colored pedunculated lesion attached to the body by a narrow stalk. These are common lesions in the elderly. <i>(<b>A</b> from Kumar V, Cotran RS, Robbins SL: Robbins Basic Pathology, 7th ed. Philadelphia, Saunders, 2003, p 799, Fig. 22-13A; <b>B</b> and <b>C</b> from Lookingbill D, Marks J: Principles of Dermatology, 3rd ed. Philadelphia, WB Saunders, 2000, pp 350 and 83, Figs. 25-5 and 6-12, respectively; <b>D</b> courtesy of R.A. Marsden, MD, St. George's Hospital, London; <b>E</b> courtesy of A. du Vivier, MD, King's College Hospital, London; <b>F</b> from Habif T: Clinical Dermatology, 4th ed. St. Louis, Mosby, 2004.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-024-f007.jpg" class="SCImage"><div> <b>A,</b> Actinic (solar) keratosis. Note the pearly gray-white hyperkeratotic lesion (<i>arrow</i>) on the hand. The other lesions (<i>circles</i>) are good examples of solar lentigo. Both of these lesions are common in the elderly population and are located in sun-exposed areas. <b>B,</b> Basal cell carcinoma. Note the ulcerated nodular mass on the inner aspect of the nose. This is a particularly common site for this cancer that invades but does <i>not</i> metastasize. <b>C,</b> Basal cell carcinoma. This microscopic section shows multifocal nests of basophilic staining cells with peripheral palisading. This section does not show a connection with the basal cell layer of skin; however, these tumors arise from multifocal locations and extend into the dermis. <b>D,</b> Squamous cell carcinoma. Note the nodular, hyperkeratotic lesion occurring on the ear. This is a common site for this cancer in the elderly population. <i>Arrow</i> shows metastasis to a lymph node. <i>(<b>A</b> courtesy of R.A. Marsden, MD, St. George's Hospital, London; <b>B</b> from Savin JA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, p 104, Fig. 4-27; <b>C</b> from Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 137, Fig. 4-60; <b>D</b> from Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 851, Fig. 22-17.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-024-f008.jpg" class="SCImage"><div> <b>A,</b> Polymorphous light eruption. Note the erythematous papules and vesicles on the sun-exposed skin. <b>B,</b> Atopic dermatitis. Note the erythematous, scaling rash on the cheeks and chin of this infant. Also note the scaling rash on the scalp, which is cradle cap (seborrheic dermatitis). <b>C,</b> Atopic dermatitis. Note the erythematous, scaling rash with thickening of the skin (lichenification) from constant scratching in the elbow flexure. <b>D,</b> Poison ivy. Note the acute eczematous rash with vesicle formation. <b>E,</b> Schematic of a suprabasal vesicle (e.g., pemphigus vulgaris). See text for discussion. <b>F,</b> Schematic of a subepidermal vesicle (e.g., bullous pemphigoid). See text for discussion. <b>G,</b> Bullous pemphigoid. Note the tense bullae. <b>H,</b> Lichen planus. Note the flat-topped violaceous papules. <b>I,</b> Psoriasis: The elbow shows a flat, salmon-colored plaque covered by white to silver-colored scales. <b>J,</b> Nail pitting in psoriasis. The nails show pitting and separation of the distal nail plate (onycholysis). <b>K,</b> Pityriasis rosea. Note the erythematous, scaly papules and plaques following the lines of cleavage of the skin ("Christmas tree" distribution). The initial herald patch was present in the left supraclavicular region. <b>L,</b> Erythema multiforme. The palms show the classic target lesions with three zones of color. <b>M,</b> Erythema nodosum. Note the raised, erythematous nodular lesions on the anterior shins. This is commonly associated with coccidioidomycosis. <b>N,</b> Granuloma annulare. Note the erythematous, annular plaque on the dorsum of the hands. There is an increased association of this skin lesion with diabetes mellitus. <b>O,</b> Urticaria. One of the manifestations of urticaria is dermatographism. In this case, there is swelling with the word HIVE. <b>P,</b> Cherry angiomas. Note the red, papular lesions on the chest. These are extremely common in the elderly population. <b>Q,</b></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-024-f009.jpg" class="SCImage"><div> <b>A,</b> Erythema toxicum. Note the yellow-white papules and pustules with a surrounding erythematous flare over the chest and arms of this newborn. <b>B,</b> Sebaceous gland hyperplasia. Note the yellow papules on the nose of the newborn. <b>C,</b> Milia. Note the white papules on the face of the newborn. <b>D,</b> Miliaria crystallina. Note the clear vesicles on the skin of the newborn. <b>E,</b> Miliaria rubra. Note the erythematous maculopapular rash on the face of the newborn. <b>F,</b> Mongolian spot. Note the area of black discoloration above the crease of the buttocks in the newborn. <i>(<b>A</b>, <b>B</b>, and <b>D</b> from Kliegman RM, Jenson HB, Behrman RE, Stanton BF: Nelson's Textbook of Pediatrics, 18th ed. Philadelphia, Saunders Elsevier, 2007, pp 2662, 2661, 2725, Figs. 646-3, 646-1, 660-1, respectively; <b>C</b> from Seidel HM, Ball JW, Danis JE, Benedict GW: Mosby's Guide to Physical Examination, 6th ed. St. Louis, Mosby Elsevier, 2006, p 199, Fig. 8-25; <b>E</b> from Habif T: Clinical Dermatology, 4th ed. St. Louis, Mosby, 2004; <b>F</b> from Lemmi FO, Lemmi CAE: Physical Assessment Findings CD-ROM, Philadelphia, WB Saunders, 2000.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f001.jpg" class="SCImage"><div> Cerebral edema. Note the widening and flattening of the gyri and the narrowing of the sulci. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 449, Fig. 19-11.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f010.jpg" class="SCImage"><div> Adenoma sebaceum (angiofibromas) in tuberous sclerosis. Note the reddish brown papules on the nose, cheeks, and chin. <i>(Courtesy of R.A. Marsden, MD, St. George's Hospital, London.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f011.jpg" class="SCImage"><div> Shagreen patch in tuberous sclerosis. Note the irregular area of white skin (leukoderma) with the typical ash-leaf pattern of a shagreen patch. <i>(From Lookingbill DP, Marks JG: Principles of Dermatology, 3rd ed. Philadelphia, Saunders, 2000, p 234, Fig. 14-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f012.jpg" class="SCImage"><div> Brain contusion. The contrecoup injury involves the frontal and temporal lobes (<i>left arrows</i>), while the coup lesion (site of impact) involves the cerebellum (<i>right arrow</i>). <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 403, Fig. 9-6.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f013.jpg" class="SCImage"><div> <b>A,</b> Schematic of epidural hematoma and subdural hematoma. <b>B,</b> Epidural hematoma. Note the blood is located on top of the dura (<i>arrow</i>). <b>C,</b> Subdural hematoma. The reflected dura shows the outer membrane of an organized venous clot covering the convexity of the brain. <i>(<b>A</b> from Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 871, Fig. 23-13A; <b>B</b> courtesy of Dr. Raymond D. Adams, Massachusetts General Hospital, Boston; <b>C</b> from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 405, Fig. 19-20.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f014.jpg" class="SCImage"><div> Red neurons. Note the brightly eosinophilic staining cells with the pyknotic nuclei within spaces representing apoptotic neurons. <i>(From Burger PC, Scheithauer BW, Vogel KS: Surgical Pathology of the Nervous System, 4th ed. London, Churchill Livingstone, 2002, p 415, Fig. 7-34.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f015.jpg" class="SCImage"><div> Atherosclerotic stroke showing necrotic areas at the periphery of the cerebral cortex in the distribution of the middle cerebral artery. <i>Arrows</i> are located at the line of demarcation between normal and infarcted tissue. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 408, Fig. 19-25A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f016.jpg" class="SCImage"><div> Cholesterol embolus to retinal artery. Note the yellow embolus trapped at the bifurcation of the retinal artery (<i>arrow</i>). This produces a sudden, painless loss of vision ("curtain coming down") followed in a variable period of time by restoration of vision ("curtain coming up") as the embolus dislodges. This is called amaurosis fugax. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 271, Fig. 10-113.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f017.jpg" class="SCImage"><div> Embolic stroke showing a wedge-shaped hemorrhagic infarction (<i>arrow</i>) along the periphery of the cerebral cortex in the distribution of the middle cerebral artery. It is hemorrhagic because blood flow was reestablished when the embolus dislodged and converted a pale infarct to a hemorrhagic infarct. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 408, Fig. 19-25B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f018.jpg" class="SCImage"><div> Intracerebral hemorrhage, showing a large blood clot within the basal ganglia area of the brain. <i>(From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 506, Fig. 21-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f019.jpg" class="SCImage"><div> Schematic of locations of berry aneurysms in the circle of Willis. See text for discussion. <i>(From Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 867, Fig. 23-9.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f002.jpg" class="SCImage"><div> Optic disk with papilledema showing loss of the disk margin and hard exudates (white streaks). <i>(From Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, p 160, Fig. 9-4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f020.jpg" class="SCImage"><div> Subarachnoid hemorrhage. Note the presence of blood covering the surface of the brain. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 470, Fig. 19-77.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f021.jpg" class="SCImage"><div> Lacunar infarcts. The <i>arrows</i> show multiple small cystic spaces (liquefactive necrosis) that are most prominent in the basal ganglia. Sections under these lesions showed hyaline arteriolosclerosis. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 408, Fig. 19-28.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f022.jpg" class="SCImage"><div> Bacterial meningitis showing engorged blood vessels and a creamy exudate covering the surface of the pia mater. <i>(From Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, p 196, Fig. 11-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f023.jpg" class="SCImage"><div> Cerebral abscess showing a cystic mass lined by necrotic, purulent material. <i>(From Burger PC, Scheithauer BW, Vogel KS: Surgical Pathology of the Nervous System, 4th ed. London, Churchill Livingstone, 2002, p 121, Fig. 3-17.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f024.jpg" class="SCImage"><div> <b>A,</b> Congenital cytomegalovirus encephalitis. The <i>arrows</i> show many chalky periventricular calcifications (dystrophic calcification). <b>B,</b> Herpes simplex encephalitis. The basal view shows hemorrhagic necrosis of the right temporal lobe. Cerebral edema is also present. <b>C,</b> HIV encephalitis. Note the numerous multinucleated microglial cells, which is a characteristic finding in HIV encephalitis, the cause of AIDS dementia. <b>D,</b> Rabies. The Purkinje cells have intracytoplasmic, eosinophilic inclusions (<i>arrows</i>) called Negri bodies. <i>(<b>A</b> and <b>C</b> from Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, pp 476, 477, Figs. 19-94, 19-97, respectively; <b>B</b> from Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, p 208, Fig. 11-15; <b>D</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1375, Fig. 28-25.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f025.jpg" class="SCImage"><div> Spongiform encephalopathy in Creutzfeldt-Jakob disease showing classic "bubbles and holes" of the neuropil cell bodies. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 412, Fig. 19-41.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f026.jpg" class="SCImage"><div> <b>A,</b> <i>Cryptococcus</i>. India ink preparation showing large capsules surrounding budding yeast cells. <b>B,</b> <i>Mucor</i> species (zygomycosis). Note the broad, aseptate hyphae that have wide-angled branching. <b>C,</b> Neurocysticercosis. Note the multiple cysts located between the gray and white mater. <b>D,</b> Toxoplasmosis. Note the cyst (<i>arrow</i>) filled with bradyzoites. <b>E,</b> Toxoplasmosis. The computed tomographic scan shows multiple enhancing lesions. Toxoplasmosis is the most common space-occupying lesion in the brain in AIDS. It can be confused with primary central nervous system lymphoma. <i>(<b>A</b> and <b>B</b> from Murray PR, Shea YR: Medical Microbiology, 2nd ed. St. Louis, Mosby, 2002, pp 787, 794, Figs. 75-8, 75-18, respectively; <b>C</b> from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 411, Fig. 19-38; <b>D</b> from Burger PC, Scheithauer BW, Vogel KS: Surgical Pathology of the Nervous System, 4th ed. London, Churchill Livingstone, 2002, p 143, Fig. 3-78; <b>E</b> from Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, p 216, Fig. 11-23.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f027.jpg" class="SCImage"><div> <b>A,</b> Multiple sclerosis, gross appearance. The brain shows multiple areas of demyelinated white mater (<i>arrows</i> pointing to gray-brown plaques). <b>B,</b> Multiple sclerosis, gross appearance. Note the periventricular location for the demyelinating plaques. <b>C,</b> Bilateral internuclear ophthalmoplegia in multiple sclerosis. When the patient is asked to look right, the right eye moves to the right and exhibits jerk nystagmus, while the left eye remains stationary. When the patient is asked to look left, the left eye moves to the left and shows jerk nystagmus, while the right eye remains stationary. These findings are due to bilateral demyelination of the medial longitudinal fasciculus. <b>D,</b> High-resolution electrophoresis of spinal fluid showing oligoclonal bands (<i>arrows</i>). Oligoclonal bands indicate the presence of demyelination. <b>E,</b> Magnetic resonance image showing extensive demyelination (white areas). <i>(<b>A</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1383, Fig. 28-32; <b>B</b> from Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 480, Fig. 19-105; <b>C, D,</b> and <b>E</b> from Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, pp 183, 187, 188, Figs. 10-8, 10-14, 10-17, respectively.</i>)</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f028.jpg" class="SCImage"><div> Central pontine myelinolysis. Note the central area of demyelination in the pons. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 413, Fig. 19-45.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f029.jpg" class="SCImage"><div> Neurofibrillary tangle. The stain shows a neuron with neurofilaments (<i>arrow</i>) composed of hyperphosphorylated tau protein. These are present in Alzheimer's disease. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 481, Fig. 19-110.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f003.jpg" class="SCImage"><div> Brain herniations. See text for discussion. <i>(Adapted from Fishman RA: Brain edema. N Engl J Med 1975; 293: 706 in Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 862, Fig. 23-4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f030.jpg" class="SCImage"><div> Senile plaque (<i>arrow</i>) shows an eosinophilic center with peripherally located distended neuronal processes (neurites). Like neurofibrillary tangles, these are present in Alzheimer's disease. <i>(From Burger PC, Scheithauer BW, Vogel KS: Surgical Pathology of the Nervous System, 4th ed. London, Churchill Livingstone, 2002, p 428, Fig. 8-9.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f031.jpg" class="SCImage"><div> Substantia nigra in Parkinson disease. <b>A,</b> The pigmentation in the substantia nigra of the midbrain is markedly diminished, when compared to the normal amount of pigmentation (<b>B</b>). <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 419, Fig. 19-67.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f032.jpg" class="SCImage"><div> Huntington's disease. The coronal section (<b>B</b>) shows atrophy of the caudate, putamen, and globus pallidus when compared with a normal coronal section (<b>A</b>). <i>(From Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, p 156, Fig. 8-19A and B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f033.jpg" class="SCImage"><div> Wilson's disease. Note cavitary necrosis of the putamen on both sides of the brain. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 413, Fig. 19-43.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f034.jpg" class="SCImage"><div> Wernicke's encephalopathy showing hemorrhage and discoloration of mamillary bodies and the wall of the third ventricle. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 413, Fig. 19-43.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f035.jpg" class="SCImage"><div> <b>A,</b> Glioblastoma multiforme showing hemorrhage and necrosis in the brain parenchyma and spreading into the adjacent hemisphere via the corpus callosum. <b>B,</b> Meningioma. Note the parasagittal multilobular tumor that is attached to the overlying dura. The tumor compresses the underlying surface of the brain. <b>C,</b> Meningioma. Note the swirling meningothelial cells and numerous basophilic staining psammoma bodies. <b>D,</b> Ependymoma of fourth ventricle. Note the hemorrhagic mass filling and expanding the fourth ventricle. <b>E,</b> Medulloblastoma. In the cerebellum there is a centrally located hemorrhagic tumor with necrosis that has almost compressed shut the fourth ventricle. <b>F,</b> Brain metastasis. The magnetic resonance image shows multiple nodular enhancing masses of varying sizes representing metastases from a breast cancer. <i>(<b>A</b> from Damjanov I, Linder J: Anderson's Pathology, 10th ed. St. Louis, Mosby, 1996, p 2750, Fig. 77-120; <b>B</b> and <b>C</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1409, Fig. 28-48A and 28-48B, respectively; <b>D</b> from Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 487, Fig. 19-127; <b>E</b> from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 424, Fig. 19-82; <b>F</b> from Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 349, Fig. 1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f036.jpg" class="SCImage"><div> Right-sided Bell's palsy showing inability to fully close the eye (<b>A</b>) and drooping of the corner of the mouth (<b>B</b>). <i>(From Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, p 77, Fig. 4-24A and B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f037.jpg" class="SCImage"><div> Schematic of lower and upper motor neuron Bell's palsy. See text for discussion. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 677, Fig. 21-16.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f038.jpg" class="SCImage"><div> Acoustic neuroma showing spindle-shaped cells with alternating dark and light areas. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 432, Fig. 19-107.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f039.jpg" class="SCImage"><div> <b>A,</b> Ulnar nerve injury. Note the claw hand due to an opposed action of the long flexors and extensors of the fingers. The ink markings show the distribution of impaired sensation. <b>B,</b> Radial nerve injury. Note the wrist drop. The ink markings show the distribution of impaired sensation. <b>C,</b> Effect of carpal tunnel syndrome on the median nerve. See text for discussion. <b>D,</b> <i>Arrows</i> show atrophy of thenar eminence. <b>E,</b> Common peroneal nerve injury. Note the foot drop. The ink markings show the distribution of impaired sensation. <b>F,</b> Erb-Duchenne palsy. Note how the arm is internally rotated and the forearm pronated producing a "waiter's tip" deformity. The ink markings show the distribution of impaired sensation of the outer side of the upper arm. <i>(<b>A, B, E,</b> and <b>F</b> from Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, pp 337, 334, 338, 332, Figs. 42.8, 42.4, 42.9, 42.2, respectively; <b>C</b> from Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 2008, Fig. 285-5; <b>D</b> from Perkin GD: Mosby's Color Atlas and Text of Neurology. St. Louis, Mosby, 2002, p 224, Fig. 12.10A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f004.jpg" class="SCImage"><div> Cerebellar coning. Note the notching in the cerebellar tonsils (<i>arrows</i>) due to downward displacement of the cerebellar tonsils through the foramen magnum. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 312, Fig. 39-2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f040.jpg" class="SCImage"><div> <b>A,</b> Arcus senilis. Note the gray-white ring around the perimeter of the cornea. <b>B,</b> Bacterial conjunctivitis. Note the conjunctival hemorrhage and pus. <b>C,</b> Herpes simplex virus keratoconjunctivitis. The special stain highlights the dendritic ulcers associated with this infection. <b>D,</b> Stye. Note the swelling, erythema, and pus from this infection of the lower eyelid. <b>E,</b> Chalazion. Note the swelling of the eyelid and absence of pus and conjunctival irritation, which distinguishes a chalazion from a stye. <b>F,</b> Orbital fracture. Note the periorbital swelling and ecchymoses giving the appearance of "raccoon" eyes. <b>G,</b> Pinguecula. Note the yellow-white conjunctival tissue on the temporal side of the conjunctiva. It extends to the junction of the cornea and sclera but it does <i>not</i> extend onto the cornea, unlike a pterygium. <b>H,</b> Central retinal artery occlusion. Note the generalized pallor of the optic disk and narrowed arteries. There is a cherry red spot on the macula, which is to the right of the optic disk. There is no boxcar segmentation in the retinal veins. <b>I,</b> Central retinal vein occlusion. Note the numerous flame hemorrhages in the retina as well as swelling of the optic disk. <b>J,</b> Schematic of the eye. Aqueous humor is produced by the ciliary body from which it flows into the anterior chamber and then out through a spongy tissue at the front of the eye called the trabecular meshwork into a drainage canal (<i>circle</i>). Glaucoma is an increase in aqueous pressure. In open-angle glaucoma, fluid cannot flow effectively through the trabecular meshwork. In acute angle-closure glaucoma there is narrowing of the anterior chamber caused by forward displacement of the ciliary body (<i>arrow</i>). <b>K,</b> Optic nerve atrophy showing a pale optic disk. <b>L,</b> Macular degeneration. Note the yellow-white deposits (drusen) in the macula. <b>M,</b> Cytomegalovirus retinitis in AIDS. Note the nu</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f041.jpg" class="SCImage"><div> Otitis media. Note the bulging, erythematous tympanic membrane. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 314, Fig. 11-29.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f042.jpg" class="SCImage"><div> Otitis externa. Note the inflammatory exudate in the external canal. <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 314, Fig. 11-26.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f005.jpg" class="SCImage"><div> Hydrocephalus and Parinaud's syndrome. Note the increased head circumference and paralysis of upward gaze in this newborn with stenosis of the aqueduct of Sylvius. (<i>Courtesy of Dr. Albert Biglan, Children's Hospital of Pittsburgh.</i>)</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f006.jpg" class="SCImage"><div> Anencephaly showing absence of the brain and opening of the spinal canal. (<i>From Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 126, Fig. 5-23B</i>.)</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f007.jpg" class="SCImage"><div> Types of spina bifida: spina bifida occulta (<b>A</b>), meningocele (<b>B</b>), meningomyelocele (<b>C</b>). <i>(From Moore NA, Roy WA: Rapid Review Gross and Developmental Anatomy, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 12, Fig. 1-13.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f008.jpg" class="SCImage"><div> Syringomyelia. Note the collapsed cystic cavity (syrinx) in the center of the cervical spinal cord. <i>(From Burger PC, Scheithauer BW, Vogel KS: Surgical Pathology of the Nervous System, 4th ed. London, Churchill Livingstone, 2002, p 554, Fig. 11-70.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-025-f009.jpg" class="SCImage"><div> Neurofibromatosis showing café-au-lait macule (<i>arrow</i>) and numerous pigmented, pedunculated neurofibromas. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 104, Fig. 2-86.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-003-f001.jpg" class="SCImage"><div> Chance of a sibling with haplotype A<sub>2</sub>B<sub>2</sub>C<sub>2</sub>D<sub>2</sub>/A<sub>4</sub>B<sub>4</sub>C<sub>4</sub>D<sub>4</sub> having a 0-, 1-, or 2-haplotype match in a family where the father is haplotype A<sub>3</sub>B<sub>3</sub>C<sub>3</sub>D<sub>3</sub>/A<sub>4</sub>B<sub>4</sub>C<sub>4</sub>D<sub>4</sub> and the mother is haplotype A<sub>1</sub>B<sub>1</sub>C<sub>1</sub>D<sub>1</sub>/ A<sub>3</sub>B<sub>3</sub>C<sub>3</sub>D<sub>3</sub>. Note that there is a 25% chance for a 2-haplotype match (A<sub>2</sub>B<sub>2</sub>C<sub>2</sub>D<sub>2</sub>/A<sub>4</sub>B<sub>4</sub>C<sub>4</sub>D<sub>4</sub>), a 25% chance for a 0-haplotype match (A<sub>1</sub>B<sub>1</sub>C<sub>1</sub>D<sub>1</sub>/A<sub>3</sub>B<sub>3</sub>C<sub>3</sub>D<sub>3</sub>), and a 50% chance of a 1-haplotype match (A<sub>2</sub>B<sub>2</sub>C<sub>2</sub>D<sub>2</sub>/A<sub>3</sub>B<sub>3</sub>C<sub>3</sub>D<sub>3</sub>) or (A<sub>1</sub>B<sub>1</sub>C<sub>1</sub>D<sub>1</sub>/A<sub>4</sub>B<sub>4</sub>C<sub>4</sub>D<sub>4</sub>). Using a parent as a transplant donor is considered a 1-haplotype match. An identical 2-haplotype is rarely achieved owing to crossing over between the individual loci during meiosis when homologous chromosomes line up close to each other. <i>(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998, p 63, Fig. 4-2.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-003-f002.jpg" class="SCImage"><div> <b>A,</b> Malar rash in systemic lupus erythematosus showing the butterfly-wing distribution. <b>B,</b> Raynaud's phenomenon: Raynaud's phenomenon in systemic sclerosis is due to a digital vasculitis. The usual color changes are white (this patient) to blue to red. It is one of the first signs of systemic sclerosis. <b>C,</b> Systemic sclerosis. The skin is erythematous and tightly bound. The fingertips are tapered (called sclerodactyly) and have digital infarcts (<i>arrows</i>) due to fibrosis of the digital vessels. <b>D,</b> Systemic sclerosis. Note the thinned lips and characteristic radial furrowing around the mouth giving a pursed-lip appearance. This is due to increased deposition of collagen in the subcutaneous tissue. There are also dilatations of small vessels (telangiectasia) on the face. <b>E,</b> Dermatomyositis. Note the characteristic purple papules overlying the knuckles and proximal and distal interphalangeal joints. <b>F,</b> Dermatomyositis. Note the characteristic swelling and red-mauve discoloration below the eyes. <i>(<b>A</b> from Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, Fig. 3-77; <b>B</b> from Savin JA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, p 205, Fig. 8.43; <b>C, D,</b> and <b>F</b> courtesy of R.A. Marsden, MD, St. George's Hospital, London; <b>E</b> from Firestein G, Budd RC, Harris ED, Jr: Kelley's Textbook of Rheumatology, 8th ed. Philadelphia, WB Saunders, 2008, Fig. 47-9.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-003-f003.jpg" class="SCImage"><div> <i>Pneumocystis jiroveci</i> pneumonia. This silver-impregnated cytologic smear prepared from bronchial washings in an HIV-positive patient contains numerous <i>P. jiroveci</i> cysts. Some cysts look like crushed ping-pong balls. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 56, Fig. 4-22B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-003-f004.jpg" class="SCImage"><div> Kaposi's sarcoma in HIV. Skin lesions are raised, red, and nonpruritic. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, Fig. 1-48.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-003-f005.jpg" class="SCImage"><div> Complement cascade. Refer to the text for discussion. DAF, decay accelerating factor; MAC, membrane attack complex.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-003-f006.jpg" class="SCImage"><div> Amyloidosis: This Congo red-stained section of glomerulus and tubules reveals apple-green birefringence under polarized light in areas with amyloid deposition. <i>(From Kern WF, Silva FG, Laszik ZG, et al: Atlas of Renal Pathology. Philadelphia, Saunders, 1999, p 225, Fig. 19-17.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-003-f007.jpg" class="SCImage"><div> Amyloidosis: This hematoxylin and eosin-stained slide of a glomerulus shows eosinophilic acellular amyloid material in the glomerular tuft and capillary walls. <i>(From Kern WF, Silva FG, Laszik ZG, et al: Atlas of Renal Pathology. Philadelphia, Saunders, 1999, p 225, Fig. 19-20.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f001.jpg" class="SCImage"><div> Body fluid compartments. See text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f010.jpg" class="SCImage"><div> Potassium (K<sup>+</sup>) shifts related to alkalosis (<b>A</b>) and acidosis (<b>B</b>). See text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f011.jpg" class="SCImage"><div> Electrocardiogram showing hypokalemia. A positive wave after the T wave is called a U wave (<i>arrow</i>). U waves are a sign of hypokalemia. <i>(From Goldman L, Bennet JC: Cecil Textbook of Medicine, 21st ed. Philadelphia, Saunders, 1999, Fig 102-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f012.jpg" class="SCImage"><div> Electrocardiogram showing hyperkalemia. Arrows show peaked T waves, which are a sign of hyperkalemia. <i>(From Goldman L, Bennet JC: Cecil Textbook of Medicine, 21st ed. Philadelphia, Saunders, 1999, Fig 102-8A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f013.jpg" class="SCImage"><div> Coronary artery thrombosis. In this specially stained cross-section of a coronary artery, collagen is blue and the thrombus is red. The red thrombus in the vessel lumen is composed of platelets held together by fibrin. Directly beneath the thrombus is a fibrous plaque, which stains blue. Beneath the plaque is necrotic atheromatous debris. The circle shows disruption of the fibrous plaque with cholesterol crystals extending through the wall to the lumen. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 21, Fig. 1-44.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f002.jpg" class="SCImage"><div> Osmotic shifts in hyponatremia (<b>A</b>) and hypernatremia or hyperglycemia (<b>B</b>). See text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f003.jpg" class="SCImage"><div> Patient with signs of volume depletion. The mucosal surface of the tongue is dry. Additional findings on examination were hypotension, tachycardia, and decreased skin turgor. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, Fig. 7-90.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f004.jpg" class="SCImage"><div> Dependent pitting edema showing depressions in the skin around the ankle. Pitting edema is due to an increase in vascular hydrostatic pressure or a decrease in vascular oncotic pressure (hypoalbuminemia). <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, Fig. 5-8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f005.jpg" class="SCImage"><div> Reclamation of bicarbonate in the proximal tubule. See text for description. c.a., carbonic anhydrase. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 32, Fig. 2-5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f006.jpg" class="SCImage"><div> Sodium, potassium, chloride cotransporter in the medullary segment of the thick ascending limb. See text for description. ATP, adenosine triphosphate; f, free; o, obligated. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 34, Fig. 2-6.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f007.jpg" class="SCImage"><div> Sodium-chloride cotransporter in the early distal tubule. See text for description. ATP, adenosine triphosphate. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 35, Fig. 2-7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f008.jpg" class="SCImage"><div> Sodium-potassium channels (<b>A</b>) and sodium-hydrogen ion channels (<b>B</b>) in the late distal and collecting duct. See text for description. ATP, adenosine triphosphate. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 36, Fig. 2-8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-004-f009.jpg" class="SCImage"><div> H<sup>+</sup>/K<sup>+</sup>-ATPase pump in the collecting tubule. See text for description. ATP, adenosine triphosphate. <i>(From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby Elsevier, 2008, p 37, Fig. 2-9.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f001.jpg" class="SCImage"><div> Point mutations: silent mutation (<i>A</i>), missense mutation (<i>B</i>), nonsense mutation (<i>C</i>). See text for discussion. <i>(From Pelley JW, Goljan E: Rapid Review Biochemistry, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 190, Fig. 10-11.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f010.jpg" class="SCImage"><div> Pedigrees showing complete and reduced penetrance in an autosomal dominant disorder. Complete penetrance (<b>A</b>) means that all individuals with the mutant gene express the disorder. Reduced penetrance (<b>B</b>) means that an individual has the mutant gene but does <i>not</i> express the disorder (<i>arrow</i>). The unaffected father has transmitted the disorder to his son.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f011.jpg" class="SCImage"><div> Pedigree of an X-linked recessive disorder. The affected male transmits the mutant gene on the X chromosome to both of his daughters and none of his sons. Both daughters are asymptomatic heterozygous carriers of the mutant gene. The daughter with four children has transmitted the mutant gene to 50% of her sons.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f012.jpg" class="SCImage"><div> Pedigree of an X-linked dominant disorder. In these rare disorders, female carriers and males with the mutant dominant gene express the disorder. The distribution is similar to that of X-linked recessive disorders, <i>except</i> that carrier females are symptomatic.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f013.jpg" class="SCImage"><div> Pathogenesis of trisomy 21 by nondisjunction in Down syndrome. See text for discussion. <i>(From Goljan EF: Star Series: Pathology. Philadelphia, WB Saunders, 1998, p 133, Fig. 7-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f014.jpg" class="SCImage"><div> Robertsonian translocation. See text for description.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f015.jpg" class="SCImage"><div> Down syndrome. The facial profile (<b>A</b>) shows a short stature and a small head with small nose and ears. The hand (<b>B</b>) shows a single palmar (simian) crease. (<i>From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, Figs. 7-168 and 7-172.</i>)</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f016.jpg" class="SCImage"><div> Turner's syndrome is characterized by a webbed neck. Other findings include short stature, primary amenorrhea, and delayed secondary sex characteristics (e.g., underdeveloped breasts). (<i>From Bouloux P-M: Self-Assessment Picture Tests: Medicine, Vol. 1. St. Louis, Mosby, 1996, p 45.</i>)</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f017.jpg" class="SCImage"><div> Klinefelter's syndrome is characterized by female secondary sex characteristics, including gynecomastia (breast development) and a female distribution of pubic hair. The legs are disproportionately long. (<i>From Bouloux P-M: Self-Assessment Picture Tests: Medicine, Vol. 1. St. Louis, Mosby, 1996, p 82.</i>)</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f018.jpg" class="SCImage"><div> Pedigree showing transmission of mitochondrial DNA. Affected females transmit the disorder to all their children, whereas affected males do not.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f019.jpg" class="SCImage"><div> Genetics of Angelman and Prader-Willi syndromes. See text for discussion. <i>(From Kumar V, Abbas AK, Fausto N, Mitchell RN: Robbins Basic Pathology, 8th ed. Philadelphia, Saunders Elsevier, 2007, p 251, Fig. 7-18.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f002.jpg" class="SCImage"><div> Frameshift mutation. See text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f020.jpg" class="SCImage"><div> Testicular feminization. The patient is genotypically male, but phenotypically female. The vagina ended as a blind pouch. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 321, Fig. 7-55.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f021.jpg" class="SCImage"><div> Fetal alcohol syndrome. Note the wide-spread eyes, inner epicanthal folds, short nose, hirsute forehead, and thin upper lip. <i>(From Zitelli: B: Atlas of Pediatric Physical Diagnosis, 3rd ed. St. Louis, Mosby, 1997.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f003.jpg" class="SCImage"><div> Pedigree of an autosomal recessive disorder. Both parents must have the mutant gene to transmit the disorder to their children. On average, 25% of the children of heterozygous parents are normal, 50% are asymptomatic heterozygous carriers, and 25% have the disorder.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f004.jpg" class="SCImage"><div> Alkaptonuria. In alkaptonuria, there is a deficiency of homogentisic oxidase with proximal accumulation of homogentisic acid, which turns black upon oxidation. <i>(From Pelley JW, Goljan E: Rapid Review Biochemistry, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 139, Fig. 8-4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f005.jpg" class="SCImage"><div> Galactosemia: See <xref xref="T005002" type="TABLE">Table 5-2</xref> for information. GALT, galactose-1-phosphate uridyltransferase; P, phosphate; UDP, uridine diphosphate. <i>(From Pelley JW, Goljan E: Rapid Review Biochemistry, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 104, Fig. 6-10.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f006.jpg" class="SCImage"><div> Hereditary fructose intolerance. See <xref xref="T005002" type="TABLE">Table 5-2</xref> for information. DHAP, dihydroxyacetone phosphate; P, phosphate. <i>(From Pelley JW, Goljan E: Rapid Review Biochemistry, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 104, Fig. 6-11.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f007.jpg" class="SCImage"><div> Homocystinuria. See text for discussion. CH<sub>3</sub>, methyl group. <i>(From Pelley JW, Goljan E: Rapid Review Biochemistry, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 143, Fig. 8-5.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f008.jpg" class="SCImage"><div> Sphingolipid degeneration. See <xref xref="T005003" type="TABLE">Table 5-3</xref> for discussion of selected sphingolipidoses. (<i>From Pelley JW, Goljan E: Rapid Review Biochemistry, 2nd ed. St. Louis, Mosby Elsevier, 2007, p 104, Fig. 6-11.</i>)</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-005-f009.jpg" class="SCImage"><div> Hurler syndrome. Note the coarse facial features and short neck. (<i>From Seidel HM, Ball JW, Danis JE, Benedict GW: Mosby's Guide to Physical Examination, 6th ed. St. Louis, Mosby Elsevier, 2006, p 273, Fig. 10-26</i>.)</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-006-f001.jpg" class="SCImage"><div> Alcohol metabolism. See text for discussion. DHAP, dihydroxyacetone phosphate; NAD<sup>+</sup>, nicotinamide adenine dinucleotide; NADH, reduced nicotinamide adenine dinucleotide; βOHB, β-hydroxybutyric acid; TG, triglyceride. <i>(From Pelley JW, Goljan EF: Rapid Review Biochemistry, 2nd ed. St. Louis, Mosby, 2007, p 172, Fig. 9-6.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-006-f002.jpg" class="SCImage"><div> <b>A,</b> Black widow spider. Note the glossy black color and the characteristic ventral red hourglass abdominal marking. <b>B,</b> Brown recluse spider. Note the yellow-brown body and violin-shaped dark brown marking on the dorsal surface of the spider. <b>C,</b> Scorpion. <i>Centruroides</i> species are the most poisonous scorpions in the United States. <i>(<b>A</b> from Goldstein BG: Practical Dermatology, 2nd ed. St. Louis, Mosby, 1997, p 69, Fig. 6-11; <b>B,</b> courtesy of Professor H. Schenone, from Peters W: A Colour Atlas of Arthropods in Clinical Medicine. London, Wolfe, 1992; <b>C,</b> courtesy of Dr. J.C. Cockendolpher, from Peters W: A Colour Atlas of Arthropods in Clinical Medicine. London, Wolfe, 1992.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-007-f001.jpg" class="SCImage"><div> Kwashiorkor and marasmus. <i>Left,</i> Child with kwashiorkor, showing dependent pitting edema involving the lower legs. <i>Right,</i> Child with marasmus, showing "broomstick" extremities with loss of muscle mass and subcutaneous tissue. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 343, Fig. 7-138.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-007-f002.jpg" class="SCImage"><div> Anorexia nervosa. Note the loss of muscle and subcutaneous tissue consistent with total calorie deprivation. <i>(From Forbes C, Jackson W: Color Atlas and Text of Clinical Medicine, 2nd ed. St. Louis, Mosby, 2003, p 344, Fig. 7-141.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-007-f003.jpg" class="SCImage"><div> Vitamin D metabolism. See text for discussion.</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-007-f004.jpg" class="SCImage"><div> <b>A,</b> Squamous metaplasia of conjunctiva (Bitot's spot) in vitamin A deficiency. Note the raised white area on the conjunctiva (<i>arrow</i>) encroaching on the cornea. <b>B,</b> Follicular hyperkeratosis in vitamin A deficiency. Note the "goose-bump" appearance of the raised, hyperkeratotic lesions. <b>C,</b> Child with rickets. Note the bow legs. <i>(<b>A</b> reprinted with permission from Oomen HAPC: Vitamin A deficiency, xerophthalmia and blindness. Nutr Rev 1974;32:161-166, Wiley-Blackwell; <b>B</b> from Morgan SL, Weinsier RL: Fundamentals of Clinical Nutrition, 2nd ed. St. Louis, Mosby, 1998; <b>C</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 8th ed. Philadelphia, WB Saunders, 2007, p 455, Fig. 8-21.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-007-f005.jpg" class="SCImage"><div> <b>A,</b> Pellagra. Note the areas of irregular hyperpigmented skin. <b>B,</b> Perifollicular hemorrhage in vitamin C deficiency. The areas of hemorrhage surround hair follicles. <b>C,</b> Corkscrew hairs in vitamin C deficiency. Note the coiled hairs lying within plugged follicles. <b>D,</b> Gums showing the effects of scurvy. The swelling, inflammation, and bleeding of the gingival papillae are prominent. <i>(<b>A</b> and <b>D</b> from Morgan SL, Weinsier RL: Fundamentals of Clinical Nutrition, 2nd ed. St. Louis, Mosby, 1998; <b>B</b> from Callen JP, Paller AS, Greer KE, Swinyer LJ: Color Atlas of Dermatology, 2nd ed. Philadelphia, WB Saunders, 2000; <b>C</b> from Savin JA, Hunter JAA, Hepbum NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, p 85, Fig. 3-8.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-008-f001.jpg" class="SCImage"><div> <b>A,</b> Tubular adenoma (adenomatous polyp) of the colon. Note the fibrovascular stalk (<i>arrow</i>) lined by normal colonic mucosa and a branching head surfaced by dysplastic (blue-staining) epithelial glands. <b>B,</b> Lipoma showing a well-circumscribed yellow tumor. <b>C,</b> Cystic teratoma of the ovary, showing the cystic nature of the tumor. Hair is present, and a tooth is visible (<i>arrow</i>). <b>D,</b> Squamous cell carcinoma. The many well-differentiated foci of eosinophilic-staining neoplastic cells produce keratin in layers (keratin pearls). <b>E,</b> Adenocarcinoma. Irregular glands infiltrate the stroma. The nuclei lining the gland lumens are cuboidal and contain nuclei with hyperchromatic nuclear chromatin. Many of the gland lumens contain secretory material (<i>arrow</i>). <b>F,</b> Osteogenic sarcoma of the distal femur. The light-colored mass of tumor in the metaphysis abuts the epiphyseal plate (<i>arrow</i>) and has spread laterally out through the cortex and into the surrounding tissue. <i>(<b>A</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 860, Fig. 17-57A; <b>B</b> and <b>C</b> from Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, pp 77, 79, Figs. 4-7, 4-11, respectively; <b>D</b> from Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 302, Fig. 13-35; <b>E</b> and <b>F</b> from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, pp 139, 369, Figs. 7-59, 17-35B, respectively.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-008-f002.jpg" class="SCImage"><div> <b>A,</b> Radionuclide scan. Radionuclide uptake is increased throughout the skeleton, with a very heavy uptake in the vertebral column. The patient had a primary breast cancer, which is the most common cancer metastatic to bone. <b>B,</b> Prostate cancer metastatic to the vertebral column. Multiple white foci of metastatic prostate cancer produce an osteoblastic response in the bone. <b>C,</b> Radiograph showing osteoblastic metastases. Note the increased density of bone in the lower lumbar vertebra and pelvic bone in metastatic prostate cancer. <b>D,</b> Radiograph showing osteolytic lesions. Note the radiolucent areas in the midshaft of the femur (<i>arrow</i>) in metastatic breast cancer. <b>E,</b> Metastasis to the liver. The liver contains multiple nodules that have a depressed central area ("umbilicated") and stellate-shaped borders. <i>(<b>A</b> from Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 70, Fig. 140; <b>B</b> from Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1052, Fig. 21-35; <b>C</b> from Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 3. London, Mosby-Wolfe, 1997, p 11, Fig. 21; <b>D</b> from Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 2187, Fig. 24-92; <b>E</b> from Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 303, Fig. 11-18.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-008-f003.jpg" class="SCImage"><div> Xeroderma pigmentosum. Note the numerous hyperpigmented lesions, nodular and scaly growths on the face. Many of these lesions are precancerous or ultraviolet light-related cancers. <i>(Courtesy of R.A. Marsden, MD, St. George's Hospital, London.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-008-f004.jpg" class="SCImage"><div> Excision-repair mechanism. <i>(From McKee PH, Calonje E, Granter SR: Pathology of the Skin with Clinical Correlations, 3rd ed. St. Louis, Elsevier Mosby, 2005, p 1228, Fig. 22.193.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-008-f005.jpg" class="SCImage"><div> Hypertrophic osteoarthropathy with finger clubbing. Note the bulbous swelling of the connective tissue in the terminal phalanxes. <i>(From Grieg JD: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 57, Fig. 8.33.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f001.jpg" class="SCImage"><div> Schematics of lipid metabolism and hyperlipoproteinemias. <b>A,</b> Chylomicron metabolism. See text for discussion. <b>B,</b> VLDL, IDL, LDL, HDL metabolism. See text for discussion. CETP, cholesterol ester transport protein; CH, cholesterol; CPL, capillary lipoprotein lipase; HDL, high density lipoprotein; IDL, intermediate density lipoprotein; LDL, low density lipoprotein; TG, triglyceride; VLDL, very low density lipoprotein. <i>(From Pelley J, Goljan E: Rapid Review Biochemistry, 2nd ed. Philadelphia, Mosby, 2007, pp 126, 127, Figs. 7-8, 7-9, respectively.</i>)</div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f010.jpg" class="SCImage"><div> <b>A,</b> Mesenteric angiogram in polyarteritis nodosa. Note the numerous small aneurysms (<i>arrows</i>) in the medium-sized vessels. <b>B,</b> Kawasaki disease: Note the desquamation of the skin of the toes, which is a characteristic skin finding in this disease. <b>C,</b> Raynaud's phenomenon. Note the extreme pallor of the digits in both hands in this patient with systemic lupus erythematosus. <b>D,</b> Saddle nose deformity in Wegener's granulomatosis. Note the concavity (<i>arrow</i>) below the bridge of the nose having the appearance of a saddle. <b>E,</b> Henoch-Schönlein purpura. Multiple erythematous, raised, palpable lesions around the ankles show areas of hemorrhage into the skin overlying areas of immunocomplex vasculitis involving small vessels. <b>F</b>, Rocky Mountain spotted fever. The palm shows a few petechial lesions in this patient with a history of a tick bite. <i>(<b>A</b> from Goldman L, Ausiello D: Cecil's Textbook of Medicine, 23rd ed. Philadelphia, Saunders Elsevier, 2008, p 2054, Fig. 291-2A; <b>B</b> courtesy of J. Ross, MD, Lewisham Hospital, London; <b>C</b> from Savin JA, Hunter JAA, Hepburn NC: Diagnosis in Color: Skin Signs in Clinical Medicine. London, Mosby-Wolfe, 1997, p 205, Fig. 8.43; <b>D</b> and <b>E</b> from Bouloux P-M: Self-Assessment Picture Tests: Medicine, Vol. 3. London, Mosby-Wolfe, 1996, pp 47 and 66, Figs. 92 and 75, respectively; <b>F</b> courtesy of Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f011.jpg" class="SCImage"><div> Angiogram showing right renal artery stenosis with post-stenotic dilation (<i>arrow</i>). <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 184, Fig. 7.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f012.jpg" class="SCImage"><div> Angiogram showing bilateral renal artery fibromuscular hyperplasia. Note the beading effect in both vessels. <i>(From Katz D, Math K, Groskin S: Radiology Secrets. Philadelphia, Hanley & Belfus, 1998, p 180, Fig. 27.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f002.jpg" class="SCImage"><div> <b>A,</b> Achilles tendon xanthoma. Note the slightly yellow nodular lesions at the distal end of the Achilles tendon. <b>B,</b> Xanthelasma. Yellow, raised lesions are noted on the lower left eyelid. <b>C,</b> Palmar xanthomas. Note the yellow macules on the palm that are accentuated in the creases. <b>D,</b> Eruptive xanthomas. Note the numerous small yellow papular lesions distributed over the buttocks. <i>(<b>A</b> courtesy of A.F. Lant, MD, and J. Dequeker, MD, London; <b>B</b> from Yanoff M, Duker J: Ophthalmology, 3rd ed. St. Louis, Mosby, 2009, Fig. 12-9-18; <b>C</b> and <b>D</b> courtesy of R.A. Marsden, MD, St George's Hospital, London.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f003.jpg" class="SCImage"><div> Hyaline arteriolosclerosis. The arrow depicts eosinophilic material representing protein that has leaked through the basement membrane and deposited in the wall of an arteriole. Other neighboring arterioles demonstrate similar changes. <i>(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 32, Fig. 2-1A.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f004.jpg" class="SCImage"><div> Abdominal aortic aneurysm. The aneurysmal dilation of the aorta is just above the bifurcation of the aorta. The probe is located at the rupture site. The lumen is filled with atherosclerotic debris and clot material. Ulcerated atheromatous plaques are proximal and distal to the aneurysm. <i>(From Kumar V, Fausto N, Abbas A: Robbins and Cotran's Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 531, Fig. 11-19B.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f005.jpg" class="SCImage"><div> Syphilitic aortitis. Note the dilated aortic valve root and the irregular intimal wrinkling ("tree barking") due to scarring in the wall of the aorta. The inset shows a silver stain with spirochetes. <i>(From Klatt E: Robbins and Cotran's Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 9, Figs. 1-22 [gross picture] and 1-24 [spirochete inset].)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f006.jpg" class="SCImage"><div> <b>A,</b> Marfan syndrome. Note the arachnodactyly ("spider" fingers) in both hands. <b>B,</b> Aortic dissection. The aortic valve (AV) is bicuspid. A large, irregular tear in the intima (AD) of the aorta shows clot material beneath the surface. <b>C,</b> Type A (proximal) and type B (distal) aortic dissection. Note that the proximal type can be limited to the arch or involve the arch and distal aorta, while type B (distal) spares the proximal aorta and primarily involves the distal aorta. <b>D,</b> Radiograph of an aortic dissection. The <i>arrows</i> show widening of the aortic valve root. <i>(<b>A</b> from Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 1, Fig. 2; <b>B</b> from Grieg JD, Garden JO: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 102, Fig. 15-4; <b>C</b> from Braunwald E, Zipes DP, Libby P, Bonow RO [eds]: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed. Philadelphia, Saunders, 2004, p 1416; <b>D</b> from Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 3. London, Mosby-Wolfe, 1997, p 2, Fig. 4.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f007.jpg" class="SCImage"><div> Stasis dermatitis. Note bilateral hemorrhage and ulceration of the skin over the medial malleoli (<i>arrows</i>). <i>(From Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, p 442, Fig. 15-1.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f008.jpg" class="SCImage"><div> Lymphedema. Note the swelling of the entire arm. The patient had a modified radical mastectomy followed by radiation. <i>(From Grieg JD, Garden JO: Color Atlas of Surgical Diagnosis. London, Mosby-Wolfe, 1996, p 36, Fig. 6-29.)</i></div></html>
<html><img src="9780323068628/Images_9780323068628/M9780323068628-009-f009.jpg" class="SCImage"><div> <b>A,</b> Bacillary angiomatosis. Note the nodular red mass and satellite lesions at the periphery. <b>B,</b> Capillary hemangioma. Note the raised, red lesion above the right eyelid in this child. <b>C,</b> Hereditary telangiectasia. Note the telangiectasias scattered over the dorsal surface of the tongue. <b>D,</b> Sturge-Weber syndrome. Note the nevus flammeus ("birthmark") on the left side of the face in the distribution of cranial nerve V (trigeminal). <i>(<b>A</b> courtesy of Richard Johnson, MD, Beth Isreal Deaconess Medical Center, Boston; <b>B</b> from Habif T: Clinical Dermatology, 4th ed. St. Louis, Mosby, 2004; <b>C</b> and <b>D</b> from Swartz MH: Textbook of Physical Diagnosis, 5th ed. Philadelphia, Saunders Elsevier, 2006, pp 333, 770, Figs. 12-11, 24-8, respectively.)</i></div></html>
/***
|Name|FoldHeadings+Plugin|
|@@modified:@@|AXS,03/2011: to include an "edit" button on the side that will open the current section for editing. This is highly custom and specific to goljanpathology.tiddlyspot.com, where 'L2wrapper'-tagged tiddlers are Level 2 wrappers (meaning they are tiddlers that transclude Level 3 tiddlers, which is where the actual book content lives). Therefore, the edit button created opens up for editing the Level 3 tiddler that is transcluded under the current heading.|
|Source|http://www.TiddlyTools.com/#FoldHeadingsPlugin|
|Version|1.1.2|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|automatically turn headings into slider-like panels that can be folded/unfolded with a single click|
This plugin defines a macro that automatically converts heading-formatted content into sliders that let you expand/collapse their content by clicking on individual headings.
!!!!!Usage
<<<
{{{
<<foldHeadings opened|closed tag tag tag...>>
}}}
where: ''opened'' or ''closed'' is a keyword indicating the initial state of the sections (default: opened), and ''tag tag tag...'' is an optional list of tags to match, so that the foldable effect is only applied to tiddlers that contain one (or more) of the indicated tags.
When you place the macro in a tiddler, any heading-formatted content (i.e, "!" through "!!!!!") in that tiddler will automatically become //'fold-able'//, allowing you to expand/collapse the content that follows each heading simply by clicking on that heading. Each content section begins with the first element following a heading, and continues until either another heading is found or the end of the tiddler is reached. For example:
{{{
<<foldHeadings closed>>
}}}
is embedded in ''this'' tiddler in order to make all the headings it contains 'fold-able'. Note that the macro has been placed at the //end// of the tiddler because it only operates on *rendered* content. Thus, only headings that //precede// it in the same tiddler will become fold-able, as any headings that //follow// it are not actually rendered until //after// the macro has been processed.
You can further limit the effect of the macro within the tiddler by surrounding several headings in a "CSS class wrapper" ("""{{classname{...}}}""") or other containing DOM element (e.g., """@@display:inline;...@@""") and then embedding the {{{<<foldHeadings>>}}} macro inside that container (at the end)... only those headings that are also within that container will be made fold-able, instead of converting ''all'' the headings in that tiddler.
Conversely, if you want the fold-able ability to apply to the headings in //all// tiddlers, ''without having to alter //any// of those individual tiddlers'', you can add the macro to the end of your [[ViewTemplate]], so that it will be invoked after the content in each tiddler has been rendered, causing all headings they contain to automatically become fold-able. For example:
{{{
<span macro="foldHeadings closed"></span>
}}}
You can also limit this effect to selected tiddlers by specifying one or more tags as additional macro parameters. For example:
{{{
<span macro="foldHeadings closed systemConfig"></span>
}}}
is only applied to headings contained in //plugin tiddlers// (i.e., tiddlers tagged with <<tag systemConfig>>), while headings in other tiddlers remain unaffected by the macro, even though it is embedded in the common [[ViewTemplate]] definition.
<<<
!!!!!Revisions
<<<
2009.11.30 [1.1.2] corrected CSS 'text-weight' to 'font-weight'
2009.01.06 [1.1.1] removed hijack of scrollToSection() (see [[SectionLinksPlugin]] for equivalent code)
2008.11.17 [1.1.0] added hijack of 'scrollToSection()' function (see [[CoreTweaks]] and http://trac.tiddlywiki.org/ticket/784)
2007.12.06 [1.0.2] fix handling for empty sections when checking for sliderPanel/floatingPanel
2007.12.02 [1.0.1] fix handling when content following a heading is already a sliderPanel/floatingPanel
2007.12.01 [1.0.0] initial release
<<<
!!!!!Code
***/
//{{{
version.extensions.FoldHeadingsPlusPlugin= {major: 1, minor: 1, revision: 2, date: new Date(2009,11,30)};
config.macros.foldHeadingsPlus = {
guideText: "opened|closed className",
showtip: "click to show '%0'",
hidetip: "click to hide '%0'",
showlabel: " [more...]",
hidelabel: " [x]",
html: "<span style='font-weight:normal;font-size:80%;' class='TiddlyLinkExisting'>%0 </span>",
handler: function(place,macroName,params) {
var show=params[0] && params.shift().toLowerCase()!="closed";
if (params.length) { // if filtering by tag(s)
var here=story.findContainingTiddler(place);
if (here) var tid=store.getTiddler(here.getAttribute("tiddler"));
if (!tid || !tid.tags.containsAny(params)) return; // in a tiddler and not tagged... do nothing...
}
var elems=place.parentNode.getElementsByTagName("*");
var heads=[]; for (var i=0; i<elems.length; i++) { // get non-foldable heading elements
var n=elems[i].nodeName; var foldable=hasClass(elems[i],"foldable");
if ((n=="H1"||n=="H2"||n=="H3"||n=="H4"||n=="H5")&&!foldable)
heads.push(elems[i]);
}
for (var i=0; i<heads.length; i++) { var h=heads[i]; // for each heading element...
// find start/end of section content (up to next heading or end of content)
var start=end=h.nextSibling; while (end && end.nextSibling) {
var n=end.nextSibling.nodeName.toUpperCase();
if (n=="H1"||n=="H2"||n=="H3"||n=="H4"||n=="H5") break;
end=end.nextSibling;
}
if (start && hasClass(start,"sliderPanel")||hasClass(start,"floatingPanel")) continue; // heading is already a slider!
var span=createTiddlyElement(null,"span",null,"sliderPanel"); // create container
span.style.display=show?"inline":"none"; // set initial display state
h.parentNode.insertBefore(span,start); // and insert it following the heading element
// move section elements into container...
var e=start; while (e) { var next=e.nextSibling; span.insertBefore(e,null); if (e==end) break; e=next; }
// set heading label/tip/cursor...
h.title=(show?this.hidetip:this.showtip).format([h.textContent])
h.innerHTML=h.innerHTML+this.html.format([show?this.hidelabel:this.showlabel]);
h.style.cursor='pointer';
addClass(h,"foldable"); // so we know it been done (and to add extra styles)
/*added by AS 03,2011 */
h.style.display='inline-block';
h.style.width="100%";
jQuery(h).wrap('<div style="display:block;"></div>');
if(config.options.chkEditMode)
jQuery(span).prepend('<span class="button" style="float:right;cursor:pointer;" onclick="story.displayTiddler(this,\''+h.firstChild.textContent+'\',\'EasyEdit+Template\')">edit+</span>');
/*end add */
h.onclick=function() {
/* changed this.nextSibling -> this.parentNode.nextSibling */
var panel=this.parentNode.nextSibling; var show=panel.style.display=="none";
// update panel display state
if (config.options.chkAnimate) anim.startAnimating(new Slider(panel,show));
else panel.style.display = show?"inline":"none";
// update heading label/tip
this.removeChild(this.firstChild.nextSibling); // remove existing label
var fh=config.macros.foldHeadingsPlus; // abbreviation for readability...
this.title=(show?fh.hidetip:fh.showtip).format([this.textContent])
this.innerHTML=this.innerHTML+fh.html.format([show?fh.hidelabel:fh.showlabel]);
}
}
}
}
if (story.scrollToSection) {
Story.prototype.foldheadingsPlus_scrollToSection=Story.prototype.scrollToSection;
Story.prototype.scrollToSection=function(title,section) {
var e=this.foldheadingsPlus_scrollToSection.apply(this,arguments);
// if scrolling to a folded section heading, click to expand it
if (e && hasClass(e,'foldable') && e.nextSibling.style.display=='none') e.onclick();
}
}
//}}}
// //<<foldHeadings closed>>
/***
|Name|FontSizePlugin|
|Created by|SaqImtiaz|
|@@modified:@@|AXS,03/2011: changed the styling of the created buttons|
|Location|http://tw.lewcid.org/#FontSizePlugin|
|Version|1.0|
|Requires|~TW2.x|
!Description:
Resize tiddler text on the fly. The text size is remembered between sessions by use of a cookie.
You can customize the maximum and minimum allowed sizes.
(only affects tiddler content text, not any other text)
Also, you can load a TW file with a font-size specified in the url.
Eg: http://tw.lewcid.org/#font:110
!Demo:
Try using the font-size buttons in the sidebar, or in the MainMenu above.
!Installation:
Copy the contents of this tiddler to your TW, tag with systemConfig, save and reload your TW.
Then put {{{<<fontSize "font-size:">>}}} in your SideBarOptions tiddler, or anywhere else that you might like.
!Usage
{{{<<fontSize>>}}} results in <<fontSize>>
{{{<<fontSize font-size: >>}}} results in <<fontSize font-size:>>
!Customizing:
The buttons and prefix text are wrapped in a span with class fontResizer, for easy css styling.
To change the default font-size, and the maximum and minimum font-size allowed, edit the config.fontSize.settings section of the code below.
!Notes:
This plugin assumes that the initial font-size is 100% and then increases or decreases the size by 10%. This stepsize of 10% can also be customized.
!History:
*27-07-06, version 1.0 : prevented double clicks from triggering editing of containing tiddler.
*25-07-06, version 0.9
!Code
***/
//{{{
config.fontSize={};
//configuration settings
config.fontSize.settings =
{
defaultSize : 100, // all sizes in %
maxSize : 130,
minSize : 40,
stepSize : 10
};
//startup code
var fontSettings = config.fontSize.settings;
if (!config.options.txtFontSize)
{config.options.txtFontSize = fontSettings.defaultSize;
saveOptionCookie("txtFontSize");}
setStylesheet(".tiddler .viewer {font-size:"+config.options.txtFontSize+"%;}\n","fontResizerStyles");
//macro
config.macros.fontSize={};
config.macros.fontSize.handler = function (place,macroName,params,wikifier,paramString,tiddler)
{
var sp = createTiddlyElement(place,"span",null,"fontResizer");
sp.ondblclick=this.onDblClick;
if (params[0])
createTiddlyText(sp,params[0]);
createTiddlyButton(sp," – ","decrease font-size",this.decFont);
createTiddlyButton(sp," = ","reset font-size",this.resetFont);
createTiddlyButton(sp," + ","increase font-size",this.incFont);
}
config.macros.fontSize.onDblClick = function (e)
{
if (!e) var e = window.event;
e.cancelBubble = true;
if (e.stopPropagation) e.stopPropagation();
return false;
}
config.macros.fontSize.setFont = function ()
{
saveOptionCookie("txtFontSize");
setStylesheet(".tiddler .viewer {font-size:"+config.options.txtFontSize+"%;}\n","fontResizerStyles");
}
config.macros.fontSize.incFont=function()
{
if (config.options.txtFontSize < fontSettings.maxSize)
config.options.txtFontSize = (config.options.txtFontSize*1)+fontSettings.stepSize;
config.macros.fontSize.setFont();
}
config.macros.fontSize.decFont=function()
{
if (config.options.txtFontSize > fontSettings.minSize)
config.options.txtFontSize = (config.options.txtFontSize*1) - fontSettings.stepSize;
config.macros.fontSize.setFont();
}
config.macros.fontSize.resetFont=function()
{
config.options.txtFontSize=fontSettings.defaultSize;
config.macros.fontSize.setFont();
}
config.paramifiers.font =
{
onstart: function(v)
{
config.options.txtFontSize = v;
config.macros.fontSize.setFont();
}
};
//}}}
/***
|Name|GotoPlugin|
|Source|http://www.TiddlyTools.com/#GotoPlugin|
|Documentation|http://www.TiddlyTools.com/#GotoPluginInfo|
|Version|1.9.2|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|view any tiddler by entering it's title - displays list of possible matches|
''View a tiddler by typing its title and pressing //enter//.'' As you type, a list of possible matches is displayed. You can scroll-and-click (or use arrows+enter) to select/view a tiddler, or press escape to close the listbox to resume typing. When the listbox is not displayed, pressing //escape// clears the current input.
!!!Documentation
>see [[GotoPluginInfo]]
!!!Configuration
<<<
*Match titles only after {{twochar{<<option txtIncrementalSearchMin>>}}} or more characters are entered.<br>Use down-arrow to start matching with shorter input. //Note: This option value is also set/used by [[SearchOptionsPlugin]]//.
*To set the maximum height of the listbox, you can create a tiddler tagged with <<tag systemConfig>>, containing:
//{{{
config.macros.gotoTiddler.listMaxSize=10; // change this number
//}}}
<<<
!!!Revisions
<<<
2009.05.22 [1.9.2] use reverseLookup() for IncludePlugin
|please see [[GotoPluginInfo]] for additional revision details|
2006.05.05 [0.0.0] started
<<<
!!!Code
***/
//{{{
version.extensions.GotoPlugin= {major: 1, minor: 9, revision: 2, date: new Date(2009,5,22)};
// automatically tweak shadow SideBarOptions to add <<gotoTiddler>> macro above <<search>>
config.shadowTiddlers.SideBarOptions=config.shadowTiddlers.SideBarOptions.replace(/<<search>>/,"{{button{goto}}}\n<<gotoTiddler>><<search>>");
if (config.options.txtIncrementalSearchMin===undefined) config.options.txtIncrementalSearchMin=3;
config.macros.gotoTiddler= {
listMaxSize: 10,
listHeading: 'Found %0 matching title%1...',
searchItem: "Search for '%0'...",
handler:
function(place,macroName,params,wikifier,paramString,tiddler) {
var quiet =params.contains("quiet");
var showlist =params.contains("showlist");
var search =params.contains("search");
params = paramString.parseParams("anon",null,true,false,false);
var instyle =getParam(params,"inputstyle","");
var liststyle =getParam(params,"liststyle","");
var filter =getParam(params,"filter","");
var html=this.html;
var keyevent=window.event?"onkeydown":"onkeypress"; // IE event fixup for ESC handling
html=html.replace(/%keyevent%/g,keyevent);
html=html.replace(/%search%/g,search);
html=html.replace(/%quiet%/g,quiet);
html=html.replace(/%showlist%/g,showlist);
html=html.replace(/%display%/g,showlist?'block':'none');
html=html.replace(/%position%/g,showlist?'static':'absolute');
html=html.replace(/%instyle%/g,instyle);
html=html.replace(/%liststyle%/g,liststyle);
html=html.replace(/%filter%/g,filter);
if (config.browser.isIE) html=this.IEtableFixup.format([html]);
var span=createTiddlyElement(place,'span');
span.innerHTML=html; var form=span.getElementsByTagName("form")[0];
if (showlist) this.fillList(form.list,'',filter,search,0);
},
html:
'<form onsubmit="return false" style="display:inline;margin:0;padding:0">\
<input name=gotoTiddler type=text autocomplete="off" accesskey="G" style="%instyle%"\
title="Enter title text... ENTER=goto, SHIFT-ENTER=search for text, DOWN=select from list"\
onfocus="this.select(); this.setAttribute(\'accesskey\',\'G\');"\
%keyevent%="return config.macros.gotoTiddler.inputEscKeyHandler(event,this,this.form.list,%search%,%showlist%);"\
onkeyup="return config.macros.gotoTiddler.inputKeyHandler(event,this,%quiet%,%search%,%showlist%);">\
<select name=list style="display:%display%;position:%position%;%liststyle%"\
onchange="if (!this.selectedIndex) this.selectedIndex=1;"\
onblur="this.style.display=%showlist%?\'block\':\'none\';"\
%keyevent%="return config.macros.gotoTiddler.selectKeyHandler(event,this,this.form.gotoTiddler,%showlist%);"\
onclick="return config.macros.gotoTiddler.processItem(this.value,this.form.gotoTiddler,this,%showlist%);">\
</select><input name="filter" type="hidden" value="%filter%">\
</form>',
IEtableFixup:
"<table style='width:100%;display:inline;padding:0;margin:0;border:0;'>\
<tr style='padding:0;margin:0;border:0;'><td style='padding:0;margin:0;border:0;'>\
%0</td></tr></table>",
getItems:
function(list,val,filter) {
if (!list.cache || !list.cache.length || val.length<=config.options.txtIncrementalSearchMin) {
// starting new search, fetch and cache list of tiddlers/shadows/tags
list.cache=new Array();
if (filter.length) {
var fn=store.getMatchingTiddlers||store.getTaggedTiddlers;
var tiddlers=store.sortTiddlers(fn.apply(store,[filter]),'title');
} else
var tiddlers=store.reverseLookup('tags','excludeLists');
for(var t=0; t<tiddlers.length; t++) list.cache.push(tiddlers[t].title);
if (!filter.length) {
for (var t in config.shadowTiddlers) list.cache.pushUnique(t);
var tags=store.getTags();
for(var t=0; t<tags.length; t++) list.cache.pushUnique(tags[t][0]);
}
}
var found = [];
var match=val.toLowerCase();
for(var i=0; i<list.cache.length; i++)
if (list.cache[i].toLowerCase().indexOf(match)!=-1) found.push(list.cache[i]);
return found;
},
getItemSuffix:
function(t) {
if (store.tiddlerExists(t)) return ""; // tiddler
if (store.isShadowTiddler(t)) return " (shadow)"; // shadow
return " (tag)"; // tag
},
fillList:
function(list,val,filter,search,key) {
if (list.style.display=="none") return; // not visible... do nothing!
var indent='\xa0\xa0\xa0';
var found = this.getItems(list,val,filter); // find matching items...
found.sort(); // alpha by title
while (list.length > 0) list.options[0]=null; // clear list
var hdr=this.listHeading.format([found.length,found.length==1?"":"s"]);
list.options[0]=new Option(hdr,"",false,false);
for (var t=0; t<found.length; t++) list.options[list.length]=
new Option(indent+found[t]+this.getItemSuffix(found[t]),found[t],false,false);
if (search)
list.options[list.length]=new Option(this.searchItem.format([val]),"*",false,false);
list.size=(list.length<this.listMaxSize?list.length:this.listMaxSize); // resize list...
list.selectedIndex=key==38?list.length-1:key==40?1:0;
},
keyProcessed:
function(ev) { // utility function
ev.cancelBubble=true; // IE4+
try{event.keyCode=0;}catch(e){}; // IE5
if (window.event) ev.returnValue=false; // IE6
if (ev.preventDefault) ev.preventDefault(); // moz/opera/konqueror
if (ev.stopPropagation) ev.stopPropagation(); // all
return false;
},
inputEscKeyHandler:
function(event,here,list,search,showlist) {
if (event.keyCode==27) {
if (showlist) { // clear input, reset list
here.value=here.defaultValue;
this.fillList(list,'',here.form.filter.value,search,0);
}
else if (list.style.display=="none") // clear input
here.value=here.defaultValue;
else list.style.display="none"; // hide list
return this.keyProcessed(event);
}
return true; // key bubbles up
},
inputKeyHandler:
function(event,here,quiet,search,showlist) {
var key=event.keyCode;
var list=here.form.list;
var filter=here.form.filter;
// non-printing chars bubble up, except for a few:
if (key<48) switch(key) {
// backspace=8, enter=13, space=32, up=38, down=40, delete=46
case 8: case 13: case 32: case 38: case 40: case 46: break; default: return true;
}
// blank input... if down/enter... fall through (list all)... else, and hide or reset list
if (!here.value.length && !(key==40 || key==13)) {
if (showlist) this.fillList(here.form.list,'',here.form.filter.value,search,0);
else list.style.display="none";
return this.keyProcessed(event);
}
// hide list if quiet, or below input minimum (and not showlist)
list.style.display=(!showlist&&(quiet||here.value.length<config.options.txtIncrementalSearchMin))?'none':'block';
// non-blank input... enter=show/create tiddler, SHIFT-enter=search for text
if (key==13 && here.value.length) return this.processItem(event.shiftKey?'*':here.value,here,list,showlist);
// up or down key, or enter with blank input... shows and moves to list...
if (key==38 || key==40 || key==13) { list.style.display="block"; list.focus(); }
this.fillList(list,here.value,filter.value,search,key);
return true; // key bubbles up
},
selectKeyHandler:
function(event,list,editfield,showlist) {
if (event.keyCode==27) // escape... hide list, move to edit field
{ editfield.focus(); list.style.display=showlist?'block':'none'; return this.keyProcessed(event); }
if (event.keyCode==13 && list.value.length) // enter... view selected item
{ this.processItem(list.value,editfield,list,showlist); return this.keyProcessed(event); }
return true; // key bubbles up
},
processItem:
function(title,here,list,showlist) {
if (!title.length) return;
list.style.display=showlist?'block':'none';
if (title=="*") { story.search(here.value); return false; } // do full-text search
if (!showlist) here.value=title;
story.displayTiddler(null,title); // show selected tiddler
return false;
}
}
//}}}
/***
|Name|GotoPluginInfo|
|Source|http://www.TiddlyTools.com/#GotoPlugin|
|Documentation|http://www.TiddlyTools.com/#GotoPluginInfo|
|Version|1.9.2|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|Documentation for GotoPlugin|
''View a tiddler by typing its title and pressing //enter//.'' As you type, a list of possible matches is displayed. You can scroll-and-click (or use arrows+enter) to select/view a tiddler, or press escape to close the listbox to resume typing. When the listbox is not displayed, pressing //escape// clears the current input.
!!!!!Usage/Examples
<<<
syntax: {{{<<gotoTiddler quiet search inputstyle:... liststyle:... filter:...>>}}}
All parameters are optional.
* ''quiet'' (//keyword//)<br>list will not be automatically display as each character is typed. Use //down// or //enter// to view the list.
* ''showlist'' (//keyword//)<br>list will always be displayed, inline, directly below the input field.
* ''search'' (//keyword//)<br>adds an extra 'command item' to the list that can be used to invoke a full-text search using the entered value. This can be especially useful when no matching tiddler titles have been found.
* ''inputstyle:'' and ''liststyle:''<br>are CSS declarations that modify the default input and listbox styles, respectively. Note: the CSS styles must be surrounded by ({{{"..."}}} or {{{'...'}}}) or ({{{[[...]]}}}) (e.g., {{{liststyle:"border:1px dotted blue;color:green;..."}}}.
* ''filter:''<br>is a single tag value (or a boolean tag expression if MatchTagsPlugin is installed), and is used to limit the search to only those tiddlers matching the indicated tag or tag expression (e.g., {{{<<gotoTiddler filter:"faq or help">>}}})
{{{<<gotoTiddler>>}}}
<<gotoTiddler>>
{{{<<gotoTiddler search>>}}}
<<gotoTiddler search>>
{{{<<gotoTiddler showlist filter:"pluginInfo" liststyle:"height:10em;width:auto;">>}}}
<<gotoTiddler showlist filter:"pluginInfo" liststyle:"height:10em;width:auto;">>
<<<
!!!!!Configuration
<<<
*Match titles only after {{twochar{<<option txtIncrementalSearchMin>>}}} or more characters are entered.<br>Use down-arrow to start matching with shorter input. //Note: This option value is also set/used by [[SearchOptionsPlugin]]//.
*To set the maximum height of the listbox, you can create a tiddler tagged with <<tag systemConfig>>, containing:
//{{{
config.macros.gotoTiddler.listMaxSize=10; // change this number
//}}}
<<<
!!!!!Revisions
<<<
2009.05.22 1.9.2 use reverseLookup() for IncludePlugin
2009.04.12 1.9.1 support multiple instances with different filters by using per-element tiddler cache instead of shared static cache
2009.04.05 1.9.0 added 'showlist' parameter for inline display with listbox always visible.
2009.03.23 1.8.0 added txtIncrementalSearchMin (default=3). Avoids fetching long lists. Use down arrow to force search with short input.
2008.12.15 1.7.1 up arrow from input field now moves to end of droplist (search for input). Also, shift+enter cam now be used to quickly invoke search for text.
2008.10.16 1.7.0 in macro handler(), changed to use //named// params instead of positional params, and added optional "filter:" param for tag filtering. Removed 'insert' handling (now provided by [[QuickEditPlugin]]).
2008.10.02 1.6.1 for IE, wrap controls in a table. Corrects placement of listbox so it is below input field.
2008.10.02 1.6.0 added 'search' param for optional "Search for:" item that invokes full text search (especially useful when no title matches are found)
2008.02.17 1.5.0 ENTER key always displays tiddler based on current input regardless of whether input matches any existing tiddler
2007.10.31 1.4.3 removed extra trailing comma on last property of config.macros.gotoTiddler object. This fixes an error under InternetExplorer that was introduced 6 days ago... sure, I should have found it sooner, but... WHY DON'T PEOPLE TELL ME WHEN THINGS ARE BROKEN!!!!
2007.10.25 1.4.2 added onclick handler for input field, so that clicking in field hides the listbox.
2007.10.25 1.4.1 re-wrote getItems() to cache list of tiddlers/shadows/tags and use case-folded simple text match instead of regular expression to find matching tiddlers. This *vastly* reduces processing overhead between keystrokes, especially for documents with many (>1000) tiddlers. Also, removed local definition of replaceSelection(), now supported directly by the TW2.2+ core, as well as via backward-compatible plugin
2007.04.25 1.4.0 renamed macro from "goto" to "gotoTiddler". This was necessary to avoid a fatal syntax error in Opera (and other browsers) that require strict adherence to ECMAScript 1.5 standards which defines the identifier "goto" as "reserved for FUTURE USE"... *sigh*
2007.04.21 1.3.2 in html definition, removed DIV around droplist (see 1.2.6 below). It created more layout problems then it solved. :-(
2007.04.01 1.3.1 in processItem(), ensure that correct textarea field is found by checking for edit=="text" attribute
2007.03.30 1.3.0 tweak SideBarOptions shadow to automatically add {{{<<goto>>}}} when using default sidebar content
2007.03.30 1.2.6 in html definition, added DIV around droplist to fix IE problem where list appears next to input field instead of below it.
2007.03.28 1.2.5 in processItem(), set focus to text area before setting selection (needed for IE to get correct selection 'range')
2007.03.28 1.2.4 added prompt for 'pretty text' when inserting a link into tiddler content
2007.03.28 1.2.3 added local copy of core replaceSelection() and modified for different replace logic
2007.03.27 1.2.2 in processItem(), use story.getTiddlerField() to retrieve textarea control
2007.03.26 1.2.1 in html, use either 'onkeydown' (IE) or 'onkeypress' (Moz) event to process <esc> key sooner, to prevent <esc> from 'bubbling up' to the tiddler (which will close the current editor).
2007.03.26 1.2.0 added support for optional "insert" keyword param.
2006.05.10 1.1.2 when filling listbox, set selection to 'heading' item... auto-select first tiddler title when down/enter moves focus into listbox
2006.05.08 1.1.1 added accesskey ("G") to input field html (also set when field gets focus). Also, inputKeyHandler() skips non-printing/non-editing keys.
2006.05.08 1.1.0 added heading to listbox for better feedback (also avoids problems with 1-line droplist)
2006.05.07 1.0.0 list matches against tiddlers/shadows/tags. input field auto-completion... 1st enter=complete matching input (or show list)... 2nd enter=view tiddler. "quiet" param controls when listbox appears. handling for enter (13), escape(27), and down(40) keys. Change 'ondblclick' to 'onclick' to avoid unintended triggering of tiddler editor). Shadow titles inserted into list instead of appended to the end.
2006.05.05 0.0.0 started
<<<
/***
|Name|HTMLFormattingPlugin|
|Source|http://www.TiddlyTools.com/#HTMLFormattingPlugin|
|Documentation|http://www.TiddlyTools.com/#HTMLFormattingPluginInfo|
|Version|2.4.1|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|embed wiki syntax formatting inside of HTML content|
The ~HTMLFormatting plugin allows you to ''mix wiki-style formatting syntax within HTML formatted content'' by extending the action of the standard TiddlyWiki formatting handler.
!!!!!Documentation
>see [[HTMLFormattingPluginInfo]]
!!!!!Configuration
<<<
Use {{{<hide linebreaks>}}} within HTML content to wiki-style rendering of line breaks. To //always// omit all line breaks from the rendered output, you can set this option:
><<option chkHTMLHideLinebreaks>> ignore all line breaks
which can also be 'hard coded' into your document by adding the following to a tiddler, tagged with <<tag systemConfig>>
>{{{config.options.chkHTMLHideLinebreaks=true;}}}
<<<
!!!!!Revisions
<<<
2010.05.07 2.4.1 added chkHTMLHideLinebreaks option
| see [[HTMLFormattingPluginInfo]] for additional revision details |
2005.06.26 1.0.0 Initial Release (as code adaptation - pre-dates TiddlyWiki plugin architecture!!)
<<<
!!!!!Code
***/
//{{{
version.extensions.HTMLFormattingPlugin= {major: 2, minor: 4, revision: 1, date: new Date(2010,5,7)};
// find the formatter for HTML and replace the handler
initHTMLFormatter();
function initHTMLFormatter()
{
for (var i=0; i<config.formatters.length && config.formatters[i].name!="html"; i++);
if (i<config.formatters.length) config.formatters[i].handler=function(w) {
if (!this.lookaheadRegExp) // fixup for TW2.0.x
this.lookaheadRegExp = new RegExp(this.lookahead,"mg");
this.lookaheadRegExp.lastIndex = w.matchStart;
var lookaheadMatch = this.lookaheadRegExp.exec(w.source)
if(lookaheadMatch && lookaheadMatch.index == w.matchStart) {
var html=lookaheadMatch[1];
// if <nowiki> is present, just let browser handle it!
if (html.indexOf('<nowiki>')!=-1)
createTiddlyElement(w.output,"span").innerHTML=html;
else {
// if <hide linebreaks> is present, or chkHTMLHideLinebreaks is set
// suppress wiki-style literal handling of newlines
if (config.options.chkHTMLHideLinebreaks||(html.indexOf('<hide linebreaks>')!=-1))
html=html.replace(/\n/g,' ');
// remove all \r's added by IE textarea and mask newlines and macro brackets
html=html.replace(/\r/g,'').replace(/\n/g,'\\n').replace(/<</g,'%%(').replace(/>>/g,')%%');
// create span, let browser parse HTML
var e=createTiddlyElement(w.output,"span"); e.innerHTML=html;
// then re-render text nodes as wiki-formatted content
wikifyTextNodes(e,w);
}
w.nextMatch = this.lookaheadRegExp.lastIndex; // continue parsing
}
}
}
// wikify #text nodes that remain after HTML content is processed (pre-order recursion)
function wikifyTextNodes(theNode,w)
{
function unmask(s) { return s.replace(/\%%\(/g,'<<').replace(/\)\%%/g,'>>').replace(/\\n/g,'\n'); }
switch (theNode.nodeName.toLowerCase()) {
case 'style': case 'option': case 'select':
theNode.innerHTML=unmask(theNode.innerHTML);
break;
case 'textarea':
theNode.value=unmask(theNode.value);
break;
case '#text':
var txt=unmask(theNode.nodeValue);
var newNode=createTiddlyElement(null,"span");
theNode.parentNode.replaceChild(newNode,theNode);
wikify(txt,newNode,highlightHack,w.tiddler);
break;
default:
for (var i=0;i<theNode.childNodes.length;i++)
wikifyTextNodes(theNode.childNodes.item(i),w); // recursion
break;
}
}
//}}}
|Name|HTMLFormattingPluginInfo|
|Source|http://www.TiddlyTools.com/#HTMLFormattingPlugin|
|Documentation|http://www.TiddlyTools.com/#HTMLFormattingPluginInfo|
|Version|2.4.1|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|documentation for HTMLFormattingPlugin|
The ~HTMLFormatting plugin allows you to freely ''mix wiki-style formatting syntax within HTML formatted content'' by extending the action of the standard TiddlyWiki formatting handler.
!!!!!Usage
<<<
The shorthand Wiki-style formatting syntax of ~TiddlyWiki is very convenient and enables most content to be reasonably well presented. However, there are times when tried-and-true HTML formatting syntax allows more more precise control of the content display.
When a tiddler is about to be displayed, ~TiddlyWiki looks for tiddler content contained within {{{<html>}}} and {{{</html>}}} markers. When present, the TiddlyWiki core simply passes this content directly to the browser's internal "rendering engine" to process as ~HTML-formatted content. However, TiddlyWiki does not also process the HTML source content for any embedded wiki-formatting syntax it may contain. This means that while you can use HTML formatted content, you cannot mix wiki-formatted content within the HTML formatting.
This plugin extends the TiddlyWiki core processing so that, after the HTML formatting has been processed, all the pieces of text occuring within the HTML block are then processed one piece at a time, so that normal wiki-style formatting can be applied to the individual text pieces.
Note: To bypass this extended processing for a specific section of HTML content, embed ''{{{<nowiki>}}}'' //anywhere// inside the {{{<html>...</html>}}} delimiters, and wiki formatting will not be applied to that content.
<<<
!!!!!Line breaks
<<<
One major difference between Wiki formatting and HTML formatting is how "line breaks" are processed. Wiki formatting treats all line breaks as literal content to be displayed //as-is//. However, because HTML normally ignores line breaks and actually processes them as simple "word separators" instead, many people who write HTML include extra line breaks in their documents, just to make the "source code" easier to read.
Even though you can use HTML tags within your tiddler content, the default treatment for line breaks still follows the Wiki-style rule (i.e., all new lines are displayed as-is). When adding HTML content to a tiddler (especially if you cut-and-paste it from another web page), you should take care to avoid adding extra line breaks to the text.
If removing all the extra line breaks from your HTML content would be a big hassle, you can quickly //override the default Wiki-style line break rule// so that the line breaks use the standard HTML rules, by placing ''{{{<hide linebreaks>}}}'' //anywhere// within the HTML content. This automatically converts all line breaks to spaces before rendering the content, so that the literal line breaks will be processed as simple word-breaks instead.
Alternatively, if you //always// want to omit all line breaks from the rendered output, you can set this option:
><<option chkHTMLHideLinebreaks>> ignore all line breaks
which can also be 'hard coded' into your document by adding the following to a tiddler, tagged with <<tag systemConfig>>
>{{{config.options.chkHTMLHideLinebreaks=true;}}}
Note: this does //not// alter the actual tiddler content that is stored in the document, just the manner in which it is displayed. Any line breaks contained in the tiddler will still be there when you edit its content. Also, to include a literal line break when the ''<{{{hide linebreaks}}}>'' tag is present, you will need to use a ''<{{{br}}}>'' or ''<{{{p}}}>'' HTML tag instead of simply typing a line break.
<<<
!!!!!How it works
<<<
The TW core support for HTML does not let you put ANY wiki-style syntax (including TW macros) *inside* the {{{<html>...</html>}}} block. Everything between {{{<html>}}} and {{{</html>}}} is handed to the browser for processing and that is it.
However, not all wiki syntax can be safely passed through the browser's parser. Specifically, any TW macros inside the HTML will get 'eaten' by the browser since the macro brackets, {{{<<...>>}}} use the "<" and ">" that normally delimit the HTML/XML syntax recognized by the browser's parser.
Similarly, you can't use InlineJavascript within the HTML because the {{{<script>...</script>}}} syntax will also be consumed by the browser and there will be nothing left to process afterward. Note: unfortunately, even though the browser removes the {{{<script>...</script>}}} sequence, it doesn't actually execute the embedded javascript code that it removes, so any scripts contained inside of <html> blocks in TW are currently being ignored. :-(
As a work-around to allow TW *macros* (but not inline scripts) to exist inside of <html> formatted blocks of content, the plugin first converts the {{{<<}}} and {{{>>}}} into "%%(" and ")%%", making them "indigestible" so they can pass unchanged through the belly of the beast (the browser's HTML parser).
After the browser has done its job, the wiki syntax sequences (including the "undigested" macros) are contained in #text nodes in the browser-generated DOM elements. The plugin then recursively locates and processes each #text node, converts the %%( and )%% back into {{{<<}}} and {{{>>}}}, passes the result to wikify() for further rendering of the wiki-formatted syntax into a containing SPAN that replaces the previous #text node. At the end of this process, none of the encoded %%( and )%% sequences remain in the rendered tiddler output.
<<<
!!!!!Revisions
<<<
2010.05.07 2.4.1 added chkHTMLHideLinebreaks option
2009.01.05 2.4.0 in wikifyTextNodes(), pass w.highlightRegExp and w.tiddler to wikify() so that search term highlighting and tiddler-relative macro processing will work
2008.10.02 2.3.0 added use of {{{<nowiki>}}} marker to bypass all wikification inside a specific HTML block
2008.09.19 2.2.0 in wikifyTextNodes(), don't wikify the contents of STYLE nodes (thanks to MorrisGray for bug report)
2008.04.26 [*.*.*] plugin size reduction: more documentation moved to HTMLFormattingInfo
2008.01.08 [*.*.*] plugin size reduction: documentation moved to HTMLFormattingInfo
2007.12.04 [*.*.*] update for TW2.3.0: replaced deprecated core functions, regexps, and macros
2007.06.14 2.1.5 in formatter, removed call to e.normalize(). Creates an INFINITE RECURSION error in Safari!!!!
2006.09.10 2.1.4 update formatter for 2.1 compatibility (use this.lookaheadRegExp instead of temp variable)
2006.05.28 2.1.3 in wikifyTextNodes(), decode the *value* of TEXTAREA nodes, but don't wikify() its children. (thanks to "ayj" for bug report)
2006.02.19 2.1.2 in wikifyTextNodes(), put SPAN element into tiddler DOM (replacing text node), BEFORE wikifying the text content. This ensures that the 'place' passed to any macros is correctly defined when the macro is evaluated, so that calls to story.findContainingTiddler(place) will work as expected. (Thanks for bug report from GeoffSlocock)
2006.02.05 2.1.1 wrapped wikifier hijack in init function to eliminate globals and avoid FireFox 1.5.0.1 crash bug when referencing globals
2005.12.01 2.1.0 don't wikify #TEXT nodes inside SELECT and TEXTAREA elements
2005.11.06 2.0.1 code cleanup
2005.10.31 2.0.0 replaced hijack wikify() with hijack config.formatters["html"] and simplified recursive WikifyTextNodes() code
2005.10.09 1.0.2 combined documentation and code into a single tiddler
2005.08.05 1.0.1 moved HTML and CSS definitions into plugin code instead of using separate tiddlers
2005.07.26 1.0.1 Re-released as a plugin. Added <{{{html}}}>...</{{{nohtml}}}> and <{{{hide newlines}}}> handling
2005.06.26 1.0.0 Initial Release (as code adaptation - pre-dates TiddlyWiki plugin architecture!!)
<<<
/***
|Name:|HideWhen+Plugin|
|Description:|Allows conditional inclusion/exclusion in templates|
|Version:|3.1 ($Rev: 3919 $)|
|Date:|$Date: 2008-03-13 02:03:12 +1000 (Thu, 13 Mar 2008) $|
|Source:|http://mptw.tiddlyspot.com/#HideWhenPlugin|
|Author:|Simon Baird <simon.baird@gmail.com>|
|@@modified:@@|AXS,03/2011: added hide/show WhenThisExists to test if the current tiddler exists|
|License:|http://mptw.tiddlyspot.com/#TheBSDLicense|
For use in ViewTemplate and EditTemplate. Example usage:
{{{<div macro="showWhenTagged Task">[[TaskToolbar]]</div>}}}
{{{<div macro="showWhen tiddler.modifier == 'BartSimpson'"><img src="bart.gif"/></div>}}}
***/
//{{{
window.hideWhenLastTest = false;
window.removeElementWhen = function(test,place) {
window.hideWhenLastTest = test;
if (test) {
removeChildren(place);
place.parentNode.removeChild(place);
}
};
merge(config.macros,{
hideWhen: { handler: function(place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( eval(paramString), place);
}},
showWhen: { handler: function(place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( !eval(paramString), place);
}},
hideWhenTagged: { handler: function (place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( tiddler.tags.containsAll(params), place);
}},
showWhenTagged: { handler: function (place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( !tiddler.tags.containsAll(params), place);
}},
hideWhenTaggedAny: { handler: function (place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( tiddler.tags.containsAny(params), place);
}},
showWhenTaggedAny: { handler: function (place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( !tiddler.tags.containsAny(params), place);
}},
hideWhenTaggedAll: { handler: function (place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( tiddler.tags.containsAll(params), place);
}},
showWhenTaggedAll: { handler: function (place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( !tiddler.tags.containsAll(params), place);
}},
hideWhenExists: { handler: function(place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( store.tiddlerExists(params[0]) || store.isShadowTiddler(params[0]), place);
}},
showWhenExists: { handler: function(place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( !(store.tiddlerExists(params[0]) || store.isShadowTiddler(params[0])), place);
}},
hideWhenThisExists: { handler: function(place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( store.tiddlerExists(tiddler.title) || store.isShadowTiddler(tiddler.title), place);
}},
showWhenThisExists: { handler: function(place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( !(store.tiddlerExists(tiddler.title) || store.isShadowTiddler(tiddler.title)), place);
}},
hideWhenTitleIs: { handler: function(place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( tiddler.title == params[0], place);
}},
showWhenTitleIs: { handler: function(place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( tiddler.title != params[0], place);
}},
'else': { handler: function(place,macroName,params,wikifier,paramString,tiddler) {
removeElementWhen( !window.hideWhenLastTest, place);
}}
});
//}}}
/%<<top>><<closeAll>><<renameButton c 'Close all tiddlers'>>
<<toggleSideBar '' '' hide>><<renameButton '>' >>
<<jump j '' top>>
<<saveChanges>><<renameButton s 'Save TiddlyWiki'>>
<<newTiddler>><<renameButton n>>%/
/***
|Name|ImportTiddlersPluginInfo|
|Source|http://www.TiddlyTools.com/#ImportTiddlersPlugin|
|Documentation|http://www.TiddlyTools.com/#ImportTiddlersPluginInfo|
|Version|4.6.0|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|documentation for ImportTiddlersPlugin|
Combine tiddlers from any two TiddlyWiki documents. An interactive control panel lets you pick a source document and import selected tiddlers, with prompting for skip, rename, merge or replace actions when importing tiddlers that match existing titles. Generates a detailed report of import 'history' in ImportedTiddlers.
!!!!!Usage
<<<
{{{<<importTiddlers>>}}} or {{{<<importTiddlers core>>}}}
invokes the built-in importTiddlers macro (TW2.1.x+). If installed in documents using TW2.0.x or earlier, fallback is to use 'link' display (see below)
{{{<<importTiddlers link label tooltip>>}}}
The ''link'' keyword creates an "import tiddlers" link that when clicked to show/hide import control panel. ''label'' and ''tooltip'' are optional text parameters (enclosed in quotes or {{{[[...]]}}}, and allow you to override the default display text for the link and the mouseover help text, respectively.
{{{<<importTiddlers inline>>}}}
creates import control panel directly in tiddler content
<<importTiddlers inline>>
Enter a document URL or press "..." to select a TiddlyWiki file to import, and then press ''[open]''. //Note: There may be a delay before the list of tiddlers appears.// Use the ''[-]'', ''[+]'', or ''[=]'' links to adjust the listbox size so you can view more (or less) tiddler titles at one time.
Select one or more titles from the listbox. Use CTRL-click or SHIFT-click to select/deselect individual titles. Click on ''all'', ''new'', ''changes'', or ''differences'' to automatically select a subset of tiddlers from the list, based on a comparison of the two documents:
*''all'' selects ALL tiddlers from the import source document, even if they have not been changed.
*''new'' selects only tiddlers that are found in the import source document, but do not yet exist in the destination document
*''changes'' selects only tiddlers that exist in both documents but that are newer in the source document
*''differences'' selects all new and existing tiddlers that are different from the destination document (even if destination tiddler is newer)
Press ''[import]'' to begin copying tiddlers to the current document. If an 'inbound' tiddler matches one that already exists in the document, the import process pauses and the tiddler title is displayed in an input field, along with four push buttons: ''skip'', ''rename'', ''merge'' and ''replace''.
* to bypass importing the tiddler, press ''skip''
* to give the inbound tiddler a different name, so that both the old and new tiddlers will exist when the import is done, enter a new title in the input field and press ''rename''
* to combine the content from both tiddlers into a single tiddler so you can then edit it later to eliminate unwanted content, press ''merge''
* to overwrite the existing tiddler with the imported one (discarding the previous content), press ''[replace]''
''Import Report History''
Whenever tiddlers are imported, a report is generated into a tiddler named [[ImportedTiddlers]], recording when the latest import was performed, the number of tiddlers successfully imported, from what location, and by whom, as well as a list of the tiddlers that were processed. When more tiddlers are imported at a later time, a new report is //added// to the existing [[ImportedTiddlers]], above the previous report (i.e., at the top of the tiddler), so that a history of imports is maintained. If this record is not desired, you can delete [[ImportedTiddlers]] at any time.
Note: You can prevent a report from being generated for any given import activity by clearing the "create a report" checkbox before pressing the ''import'' button
<<<
!!!!!Installation Notes
<<<
* As of 6/27/2007, support for TW2.1.x and earlier have been moved to [[ImportTiddlersPluginPatch]]. ''//Only install the patch plugin when using TW2.1.x or earlier.//''
<<<
!!!!!Revisions
<<<
2009.10.06 4.6.0 added createTiddlerFromFile (import text files)
2009.09.27 4.5.5 in readTiddlersFromCSV(), strip \r from input and fixed handling for quoted values
2009.09.12 4.5.4 fixed 'return false' to prevent IE page transition. Also, moved html/css definitions to separate sections
2009.08.23 4.5.3 in importTiddlers(), add 'file:///' to local server.host sync field only if not already present in URL
2009.08.20 4.5.2 only use SiteURL/SiteProxy values if control panel value has not yet been set
2009.07.03 4.5.1 fixups for TW252: doHttp() doesn't return XHR and convertUTF8ToUnicode() not needed for local I/O
2009.05.04 4.5.0 import from CSV-formatted files
2009.03.04 4.4.2 in createImportPanel(), init option checkboxes so display matches internal state variables
2009.02.26 4.4.1 use macro-specific definition of $() function abbreviation (avoids conflict with JQuery)
2008.09.30 4.4.0 added fallback definition of merge() for use with TW2.0.x and TW1.2.x
2008.08.12 4.3.3 rewrite backstage and shadow tiddler definitions for easier customization
2008.08.05 4.3.2 rewrote loadRemoteFile() to eliminate use of platform-specific fileExists() function
2008.06.29 4.3.1 More layout/animation work for simpler sequential interaction. Code reduction/cleanup
2008.06.28 4.3.0 HTML and CSS cleanup and tweaks to layout. Added animation to panels
2008.06.22 4.2.0 For FireFox, use HTML with separate text+button control instead of type='file' control
2008.06.05 4.1.0 in filterByHash(), added support for boolean tag expressions using getMatchingTiddlers() (defined by MatchTagsPlugin)
2008.05.12 4.0.2 automatically tweak the backstage "import" task to add the ImportTiddlers control panel
2008.04.30 4.0.1 trim #... suffix for loading files/URLs in IE
2008.04.30 4.0.0 added source filtering (using URL paramifiers). Also, abbreviations for code-size reduction.
2008.04.13 3.9.0 added 'apply to all' checkbox for collision processing
2008.03.26 3.8.0 added support for selecting pre-defined systemServer URLs
2008.03.25 3.7.0 added support for setting 'server' fields on imported tiddlers (for later synchronizing of changes)
2008.01.03 3.6.0 in loadRemoteFile(), use lower-level doHttp() instead of loadRemoteFile() in order to support username/password access to remote server
2007.10.30 3.5.6 update [[ImportTiddlers]] shadow tiddler definition to include "inline" link
2007.06.27 3.5.5 added missing 'fields' params to saveTiddler() calls. Fixes problem where importing tiddlers would lose the custom fields. Also, moved functions for TW2.1.x to [[ImportTiddlersPluginPatch2.1.x]].
2007.06.25 3.5.4 added calls to store.suspendNotifications() and store.resumeNotifications(). Eliminates redisplay processing overhead DURING import activities
2007.04.29 3.5.3 in refreshImportList() when inbound tiddlers are loaded, change "close" button to "done", and disable certain controls to creates a modal condition, so that actions that reload tiddlers cannot be performed unless "done" is first pressed to end the mode..
2007.04.28 3.5.2 in handler(), added param support for custom link label/prompt
2007.04.19 3.5.1 in readTiddlersFromHTML(), for TW2.2 and above, use importTiddlyWiki() (new core functionality) to get tiddlers from remote file content. Also, copied updated TW21Loader.prototype.internalizeTiddler() definition from TW2.2b5 so plugin can read tiddlers from TW2.2+ even when running under TW2.1.x
2007.03.22 3.5.0 in refreshImportList(), add handling for 'select section' when a heading is selected. Makes it really easy to import by tag or date!
2007.03.21 3.4.0 split loadTiddlers functionality into separate plugin (see [[LoadTiddlersPlugin]])
2007.03.20 3.3.1 tweak to previous change to allow relative file references via http: (bypasses getLocalPath() so remote URL will be used)
2007.03.20 3.3.0 added support for local, relative file references: in loadRemoteFile(), check for fileExists(). If not found, prepend relative path and retry.
2007.02.24 3.2.1 re-labeled control panel "open" button to "load"
2007.02.09 3.2.0 loadTiddlers: added support for "noReload" tag (prevents overwriting existing tiddler, even if inbound tiddler is newer)
2007.02.08 3.1.3 loadTiddlers: added missing code and documentation for "newTags" handling (a feature change from long, long ago that somehow got lost!)
2006.11.14 3.1.2 fix macro handler parameter declaration (double-pasted param list corrupts IE)
2006.11.13 3.1.1 use apply() method to invoke hijacked core handler
2006.11.13 3.1.0 hijack built-in importTiddlers.handler() to co-exist with plugin interface. If no params or 'core' keyword, display core interface. "link" param embeds "import tiddlers" link that shows floating panel when clicked.
2006.10.12 3.0.8 in readTiddlersFromHTML(), fallback to find end of store area by matching "/body" when POST-BODY-START is not present (backward compatibility for older documents)
2006.09.10 3.0.7 in readTiddlersFromHTML(), find end of store area by matching "POST-BODY-START" instead of "/body"
2006.08.16 3.0.6 Use higher-level store.saveTiddler() instead of store.addTiddler() to avoid conflicts with adaptations that hijack low-level tiddler handling. in CreateImportPanel(), removed "refresh listbox after every tiddler change".
2006.07.29 3.0.5 added noChangeMsg to loadTiddlers processing. if not 'quiet' mode, reports skipped tiddlers.
2006.04.18 3.0.4 in loadTiddlers.handler, fixed parsing of "prompt:" param. Also, corrected parameters mismatch in loadTiddlers() callback function definition (order of params was wrong, resulting in filters NOT being applied)
2006.04.12 3.0.3 moved many display messages to macro properties for easier L10N translations via 'lingo' definitions.
2006.04.12 3.0.2 more work on 'core candidate' code. Proposed API now defines "loadRemoteFile()" for XMLHttpRequest processing with built in fallback for handling local filesystem access, and readTiddlersFromHTML() to process the resulting source HTML content.
2006.04.04 3.0.1 in refreshImportList(), when using [by tags], tiddlers without tags are now included in a new "untagged" psuedo-tag list section
2006.04.04 3.0.0 Separate non-interactive {{{<<importTiddlers...>>}}} macro functionality for incorporation into TW2.1 core and renamed as {{{<<loadTiddlers>>}}} macro. New parameters for loadTiddlers: ''label:text'' and ''prompt:text'' for link creation, ''ask'' for filename/URL, ''tag:text'' for filtering, "confirm" for accept/reject of individual inbound tiddlers. Removed support for "importReplace/importPublic" tags and "force" param (unused feature).
2006.03.30 2.9.1 when extracting store area from remote URL, look for "</body>" instead of "</body>\n</html>" so it will match even if the "\n" is absent from the source.
2006.03.30 2.9.0 added optional 'force' macro param. When present, autoImportTiddlers() bypasses the checks for importPublic and importReplace. Based on a request from Tom Otvos.
2006.03.28 2.8.1 in loadImportFile(), added checks to see if 'netscape' and 'x.overrideMimeType()' are defined (not in IE). Also, when extracting store area, look for "</body>\n</html>" and omit extra content that may have been added to the end of the file.
2006.02.21 2.8.0 added support for "tiddler:TiddlerName" filtering parameter in auto-import processing
2006.02.21 2.7.1 Clean up layout problems with IE. (Use tables for alignment instead of SPANs styled with float:left and float:right)
2006.02.21 2.7.0 Added "local file" and "web server" radio buttons. Default remote URL uses value from [[SiteURL]]. Also, added 'proxy' option, using value from [[SiteProxy]] as prefix to permit cross-domain document access via server-side scripting.
2006.02.17 2.6.0 Removed "differences only" listbox display mode, replaced with selection filter 'presets': all/new/changes/differences. fixed init of "add new tags" checkbox
2006.02.16 2.5.4 added checkbox options to control "import remote tags" and "keep existing tags" behavior, in addition to existing "add new tags" functionality.
2006.02.14 2.5.3 FF1501 corrected unintended global 't' (loop index) in importReport() and autoImportTiddlers()
2006.02.10 2.5.2 corrected unintended global variable in importReport().
2006.02.05 2.5.1 moved globals from window.* to config.macros.importTiddlers.* to avoid FireFox 1.5.0.1 crash bug when referencing globals
2006.01.18 2.5.0 added checkbox for "create a report". Default is to create/update the ImportedTiddlers report.
2006.01.15 2.4.1 added "importPublic" tag and inverted default so that auto sharing is NOT done unless tagged with importPublic
2006.01.15 2.4.0 Added support for tagging tiddlers with importSkip, importReplace, and/or importPrivate to enable/disable overwriting or sharing with others when using auto-import macro syntax. Defaults: don't overwrite existing tiddlers, and allow your tiddlers to be auto-imported by others.
2006.01.15 2.3.2 Added "ask" parameter to confirm each tiddler before importing (for use with auto-importing)
2006.01.15 2.3.1 Strip TW core scripts from import source content and load just the storeArea into the hidden IFRAME to prevent imported document's core code from being invoked. Also, when importing local documents, use convertUTF8ToUnicode() to support international characters sets.
2006.01.12 2.3.0 Reorganized code to use callback function for loading import files to support event-driven I/O via an ASYNCHRONOUS XMLHttpRequest instead of waiting for remote hosts to respond to URL requests. Added non-interactive 'batch' mode, using macro parameters to specify source path/file or URL, and select tiddlers to import. Improved messages and added optional 'quiet' switch for batch mode to eliminate //most// feedback.
2006.01.11 2.2.0 Added "[by tags]" to list of tiddlers, based on code submitted by BradleyMeck
2006.01.08 2.1.0 IMPORT FROM ANYWHERE!!! re-write getImportedTiddlers() logic to either read a local file (using local I/O), OR... read a remote file, using a combination of XML and an iframe to permit cross-domain reading of DOM elements. Adapted from example code and techniques courtesy of Jonny LeRoy.
2006.01.06 2.0.2 When refreshing list contents, fixed check for tiddlerExists() when "show differences only" is selected, so that imported tiddlers that don't exist in the current file will be recognized as differences and included in the list.
2006.01.04 2.0.1 When "show differences only" is NOT checked, import all tiddlers that have been selected even when they have a matching title and date.
2005.12.27 2.0.0 Update for TW2.0
Defer initial panel creation and only register a notification function when panel first is created
2005.12.22 1.3.1 tweak formatting in importReport() and add 'discard report' link to output
2005.12.03 1.3.0 Dynamically create/remove importPanel as needed to ensure only one instance of interface elements exists, even if there are multiple instances of macro embedding. Also, dynamically create/recreate importFrame each time an external TW document is loaded for importation (reduces DOM overhead and ensures a 'fresh' frame for each document)
2005.11.29 1.2.1 fixed formatting of 'detail info' in importReport()
2005.11.11 1.2.0 added 'inline' param to embed controls in a tiddler
2005.11.09 1.1.0 only load HTML and CSS the first time the macro handler is called. Allows for redundant placement of the macro without creating multiple instances of controls with the same ID's.
2005.10.25 1.0.5 fixed typo in importReport() that prevented reports from being generated
2005.10.09 1.0.4 combined documentation with plugin code instead of using separate tiddlers
2005.08.05 1.0.3 moved CSS and HTML definitions into plugin code instead of using separate tiddlers
2005.07.27 1.0.2 core update 1.2.29: custom overlayStyleSheet() replaced with new core setStylesheet()
2005.07.23 1.0.1 added parameter checks and corrected addNotification() usage
2005.07.20 1.0.0 Initial Release
<<<
Saving:
*Saving notes/annotations only works on a local copy of the book (see [[Local copy]])
Edit mode:
*see [[Annotating]]
Backups:
*By default, every time you save the book, a new backup is saved in the same folder. Previous backups are left in the folder as well.
*To disable backups __for the current session__, uncheck here: {{button{<<option chkSaveBackups>>}}} or in the {{{options}}} menu
*Regardless of your selection above, the next time you open the book, backups will be enabled again.
Margin notes:
*The @@color:blue;blue text@@ corresponds to the margin notes found in the paperback version of the book. Some of these blockquotes may be //slightly// misplaced relative to the content, but are mostly in the correct locations.
@@font-size:10pt;Copyright:
*All book content is copyrighted and owned by Elsevier Inc. It is displayed here strictly for non-profit, educational purposes. Distribution is prohibited. A studentconsult.com account is required to use this content.@@
/***
|Name|InlineJavascriptPlugin|
|Source|http://www.TiddlyTools.com/#InlineJavascriptPlugin|
|Documentation|http://www.TiddlyTools.com/#InlineJavascriptPluginInfo|
|Version|1.9.6|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|Insert Javascript executable code directly into your tiddler content.|
''Call directly into TW core utility routines, define new functions, calculate values, add dynamically-generated TiddlyWiki-formatted output'' into tiddler content, or perform any other programmatic actions each time the tiddler is rendered.
!!!!!Documentation
>see [[InlineJavascriptPluginInfo]]
!!!!!Revisions
<<<
2010.12.15 1.9.6 allow (but ignore) type="..." syntax
|please see [[InlineJavascriptPluginInfo]] for additional revision details|
2005.11.08 1.0.0 initial release
<<<
!!!!!Code
***/
//{{{
version.extensions.InlineJavascriptPlugin= {major: 1, minor: 9, revision: 6, date: new Date(2010,12,15)};
config.formatters.push( {
name: "inlineJavascript",
match: "\\<script",
lookahead: "\\<script(?: type=\\\"[^\\\"]*\\\")?(?: src=\\\"([^\\\"]*)\\\")?(?: label=\\\"([^\\\"]*)\\\")?(?: title=\\\"([^\\\"]*)\\\")?(?: key=\\\"([^\\\"]*)\\\")?( show)?\\>((?:.|\\n)*?)\\</script\\>",
handler: function(w) {
var lookaheadRegExp = new RegExp(this.lookahead,"mg");
lookaheadRegExp.lastIndex = w.matchStart;
var lookaheadMatch = lookaheadRegExp.exec(w.source)
if(lookaheadMatch && lookaheadMatch.index == w.matchStart) {
var src=lookaheadMatch[1];
var label=lookaheadMatch[2];
var tip=lookaheadMatch[3];
var key=lookaheadMatch[4];
var show=lookaheadMatch[5];
var code=lookaheadMatch[6];
if (src) { // external script library
var script = document.createElement("script"); script.src = src;
document.body.appendChild(script); document.body.removeChild(script);
}
if (code) { // inline code
if (show) // display source in tiddler
wikify("{{{\n"+lookaheadMatch[0]+"\n}}}\n",w.output);
if (label) { // create 'onclick' command link
var link=createTiddlyElement(w.output,"a",null,"button",wikifyPlainText(label));
var fixup=code.replace(/document.write\s*\(/gi,'place.bufferedHTML+=(');
link.code="function _out(place,tiddler){"+fixup+"\n};_out(this,this.tiddler);"
link.tiddler=w.tiddler;
link.onclick=function(){
this.bufferedHTML="";
try{ var r=eval(this.code);
if(this.bufferedHTML.length || (typeof(r)==="string")&&r.length)
var s=this.parentNode.insertBefore(document.createElement("span"),this.nextSibling);
if(this.bufferedHTML.length)
s.innerHTML=this.bufferedHTML;
if((typeof(r)==="string")&&r.length) {
wikify(r,s,null,this.tiddler);
return false;
} else return r!==undefined?r:false;
} catch(e){alert(e.description||e.toString());return false;}
};
link.setAttribute("title",tip||"");
var URIcode='javascript:void(eval(decodeURIComponent(%22(function(){try{';
URIcode+=encodeURIComponent(encodeURIComponent(code.replace(/\n/g,' ')));
URIcode+='}catch(e){alert(e.description||e.toString())}})()%22)))';
link.setAttribute("href",URIcode);
link.style.cursor="pointer";
if (key) link.accessKey=key.substr(0,1); // single character only
}
else { // run script immediately
var fixup=code.replace(/document.write\s*\(/gi,'place.innerHTML+=(');
var c="function _out(place,tiddler){"+fixup+"\n};_out(w.output,w.tiddler);";
try { var out=eval(c); }
catch(e) { out=e.description?e.description:e.toString(); }
if (out && out.length) wikify(out,w.output,w.highlightRegExp,w.tiddler);
}
}
w.nextMatch = lookaheadMatch.index + lookaheadMatch[0].length;
}
}
} )
//}}}
// // Backward-compatibility for TW2.1.x and earlier
//{{{
if (typeof(wikifyPlainText)=="undefined") window.wikifyPlainText=function(text,limit,tiddler) {
if(limit > 0) text = text.substr(0,limit);
var wikifier = new Wikifier(text,formatter,null,tiddler);
return wikifier.wikifyPlain();
}
//}}}
// // GLOBAL FUNCTION: $(...) -- 'shorthand' convenience syntax for document.getElementById()
//{{{
if (typeof($)=='undefined') { function $(id) { return document.getElementById(id.replace(/^#/,'')); } }
//}}}
/***
|Name|InlineJavascriptPluginInfo|
|Source|http://www.TiddlyTools.com/#InlineJavascriptPlugin|
|Documentation|http://www.TiddlyTools.com/#InlineJavascriptPluginInfo|
|Version|1.9.6|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|Documentation for InlineJavascriptPlugin|
''Call directly into TW core utility routines, define new functions, calculate values, add dynamically-generated TiddlyWiki-formatted output'' into tiddler content, or perform any other programmatic actions each time the tiddler is rendered.
!!!!!Usage
<<<
This plugin adds wiki syntax for surrounding tiddler content with {{{<script>}}} and {{{</script>}}} markers, so that it can be recognized as embedded javascript code. When a tiddler is rendered, the plugin automatically invokes any embedded scripts, which can be used to construct and return dynamically-generated output that is inserted into the tiddler content.
{{{
<script type="..." src="..." label="..." title="..." key="..." show>
/* javascript code goes here... */
</script>
}}}
All parameters are //optional//. When the ''show'' keyword is used, the plugin will also include the script source code in the output that it displays in the tiddler. This is helpful when creating examples for documentation purposes (such as used in this tiddler!)
__''Deferred execution from an 'onClick' link''__
<script label="click here" title="mouseover tooltip text" key="X" show>
/* javascript code goes here... */
alert('you clicked on the link!');
</script>
By including a {{{label="..."}}} parameter in the initial {{{<script>}}} marker, the plugin will create a link to an 'onclick' script that will only be executed when that specific link is clicked, rather than running the script each time the tiddler is rendered. You may also include a {{{title="..."}}} parameter to specify the 'tooltip' text that will appear whenever the mouse is moved over the onClick link text, and a {{{key="X"}}} parameter to specify an //access key// (which must be a //single// letter or numeric digit only).
__''Loading scripts from external source files''__
<script src="URL" show>
/* optional javascript code goes here... */
</script>You can also load javascript directly from an external source URL, by including a src="..." parameter in the initial {{{<script>}}} marker (e.g., {{{<script src="demo.js"></script>}}}). This is particularly useful when incorporating third-party javascript libraries for use in custom extensions and plugins. The 'foreign' javascript code remains isolated in a separate file that can be easily replaced whenever an updated library file becomes available.
In addition to loading the javascript from the external file, you can also use this feature to invoke javascript code contained within the {{{<script>...</script>}}} markers. This code is invoked //after// the external script file has been processed, and can make immediate use of the functions and/or global variables defined by the external script file.
>Note: To ensure that your javascript functions are always available when needed, you should load the libraries from a tiddler that is rendered as soon as your TiddlyWiki document is opened, such as MainMenu. For example: put your {{{<script src="..."></script>}}} syntax into a separate 'library' tiddler (e.g., LoadScripts), and then add {{{<<tiddler LoadScripts>>}}} to MainMenu so that the library is loaded before any other tiddlers that rely upon the functions it defines.
>
>Normally, loading external javascript in this way does not produce any direct output, and should not have any impact on the appearance of your MainMenu. However, if your LoadScripts tiddler contains notes or other visible content, you can suppress this output by using 'inline CSS' in the MainMenu, like this: {{{@@display:none;<<tiddler LoadScripts>>@@}}}
<<<
!!!!!Creating dynamic tiddler content and accessing the ~TiddlyWiki DOM
<<<
An important difference between TiddlyWiki inline scripting and conventional embedded javascript techniques for web pages is the method used to produce output that is dynamically inserted into the document: in a typical web document, you use the {{{document.write()}}} (or {{{document.writeln()}}}) function to output text sequences (often containing HTML tags) that are then rendered when the entire document is first loaded into the browser window.
However, in a ~TiddlyWiki document, tiddlers (and other DOM elements) are created, deleted, and rendered "on-the-fly", so writing directly to the global 'document' object does not produce the results you want (i.e., replacing the embedded script within the tiddler content), and instead will //completely replace the entire ~TiddlyWiki document in your browser window (which is clearly not a good thing!)//. In order to allow scripts to use {{{document.write()}}}, the plugin automatically converts and buffers all HTML output so it can be safely inserted into your tiddler content, immediately following the script.
''Note that {{{document.write()}}} can only be used to output "pure HTML" syntax. To produce //wiki-formatted// output, your script should instead return a text value containing the desired wiki-syntax content'', which will then be automatically rendered immediately following the script. If returning a text value is not sufficient for your needs, the plugin also provides an automatically-defined variable, 'place', that gives the script code ''direct access to the //containing DOM element//'' into which the tiddler output is being rendered. You can use this variable to ''perform direct DOM manipulations'' that can, for example:
* generate wiki-formatted output using {{{wikify("...content...",place)}}}
* vary the script's actions based upon the DOM element in which it is embedded
* access 'tiddler-relative' DOM information using {{{story.findContainingTiddler(place)}}}
Note:
''When using an 'onclick' script, the 'place' element actually refers to the onclick //link text// itself, instead of the containing DOM element.'' This permits you to directly reference or modify the link text to reflect any 'stateful' conditions that might set by the script. To refer to the containing DOM element from within an 'onclick' script, you can use "place.parentNode" instead.
<<<
!!!!!Instant "bookmarklets"
<<<
You can also use an 'onclick' link to define a "bookmarklet": a small piece of javascript that can be ''invoked directly from the browser without having to be defined within the current document.'' This allows you to create 'stand-alone' commands that can be applied to virtually ANY TiddlyWiki document... even remotely-hosted documents that have been written by others!! To create a bookmarklet, simply define an 'onclick' script and then grab the resulting link text and drag-and-drop it onto your browser's toolbar (or right-click and use the 'bookmark this link' command to add it to the browser's menu).
Notes:
*When writing scripts intended for use as bookmarklets, due to the ~URI-encoding required by the browser, ''you cannot not use ANY double-quotes (") within the bookmarklet script code.''
*All comments embedded in the bookmarklet script must ''use the fully-delimited {{{/* ... */}}} comment syntax,'' rather than the shorter {{{//}}} comment syntax.
*Most importantly, because bookmarklets are invoked directly from the browser interface and are not embedded within the TiddlyWiki document, there is NO containing 'place' DOM element surrounding the script. As a result, ''you cannot use a bookmarklet to generate dynamic output in your document,'' and using {{{document.write()}}} or returning wiki-syntax text or making reference to the 'place' DOM element will halt the script and report a "Reference Error" when that bookmarklet is invoked.
Please see [[InstantBookmarklets]] for many examples of 'onclick' scripts that can also be used as bookmarklets.
<<<
!!!!!Special reserved function name
<<<
The plugin 'wraps' all inline javascript code inside a function, {{{_out()}}}, so that any return value you provide can be correctly handled by the plugin and inserted into the tiddler. To avoid unpredictable results (and possibly fatal execution errors), this function should never be redefined or called from ''within'' your script code.
<<<
!!!!!$(...) 'shorthand' function
<<<
As described by Dustin Diaz [[here|http://www.dustindiaz.com/top-ten-javascript/]], the plugin defines a 'shorthand' function that allows you to write:
{{{
$(id)
}}}
in place of the normal standard javascript syntax:
{{{
document.getElementById(id)
}}}
This function is provided merely as a convenience for javascript coders that may be familiar with this abbreviation, in order to allow them to save a few bytes when writing their own inline script code.
<<<
!!!!!Examples
<<<
simple dynamic output:
><script show>
document.write("The current date/time is: "+(new Date())+"<br>");
return "link to current user: [["+config.options.txtUserName+"]]\n";
</script>
dynamic output using 'place' to get size information for current tiddler:
><script show>
if (!window.story) window.story=window;
var title=story.findContainingTiddler(place).getAttribute("tiddler");
var size=store.getTiddlerText(title).length;
return title+" is using "+size+" bytes";
</script>
dynamic output from an 'onclick' script, using {{{document.write()}}} and/or {{{return "..."}}}
><script label="click here" show>
document.write("<br>The current date/time is: "+(new Date())+"<br>");
return "link to current user: [["+config.options.txtUserName+"]]\n";
</script>
creating an 'onclick' button/link that accesses the link text AND the containing tiddler:
><script label="click here" title="clicking this link will show an 'alert' box" key="H" show>
if (!window.story) window.story=window;
var txt=place.firstChild.data;
var tid=story.findContainingTiddler(place).getAttribute('tiddler');
alert('Hello World!\nlinktext='+txt+'\ntiddler='+tid);
</script>
dynamically setting onclick link text based on stateful information:
>{{block{
{{{
<script label="click here">
/* toggle "txtSomething" value */
var on=(config.txtSomething=="ON");
place.innerHTML=on?"enable":"disable";
config.txtSomething=on?"OFF":"ON";
return "\nThe current value is: "+config.txtSomething;
</script><script>
/* initialize onclick link text based on current "txtSomething" value */
var on=(config.txtSomething=="ON");
place.lastChild.previousSibling.innerHTML=on?"disable":"enable";
</script>
}}}
<script label="click here">
/* toggle "txtSomething" value */
var on=(config.txtSomething=="ON");
place.innerHTML=on?"enable":"disable";
config.txtSomething=on?"OFF":"ON";
return "\nThe current value is: "+config.txtSomething;
</script><script>
/* initialize onclick link text based on current "txtSomething" value */
var on=(config.txtSomething=="ON");
place.lastChild.innerHTML=on?"enable":"disable";
</script>
}}}
loading a script from a source url:
>http://www.TiddlyTools.com/demo.js contains:
>>{{{function inlineJavascriptDemo() { alert('Hello from demo.js!!') } }}}
>>{{{displayMessage('InlineJavascriptPlugin: demo.js has been loaded');}}}
>note: When using this example on your local system, you will need to download the external script file from the above URL and install it into the same directory as your document.
>
><script src="demo.js" show>
return "inlineJavascriptDemo() function has been defined"
</script>
><script label="click to invoke inlineJavascriptDemo()" key="D" show>
inlineJavascriptDemo();
</script>
<<<
!!!!!Revisions
<<<
2010.12.15 1.9.6 allow (but ignore) type="..." syntax
2009.04.11 1.9.5 pass current tiddler object into wrapper code so it can be referenced from within 'onclick' scripts
2009.02.26 1.9.4 in $(), handle leading '#' on ID for compatibility with JQuery syntax
2008.06.11 1.9.3 added $(...) function as 'shorthand' for document.getElementById()
2008.03.03 1.9.2 corrected fallback declaration of wikifyPlainText() (fixes Safari "parse error")
2008.02.23 1.9.1 in onclick function, use string instead of array for 'bufferedHTML' (fixes IE errors)
2008.02.21 1.9.0 output from 'onclick' scripts (return value or document.write() calls) are now buffered and rendered into into a span following the script. Also, added default 'return false' handling if no return value provided (prevents HREF from being triggered -- return TRUE to allow HREF to be processed). Thanks to Xavier Verges for suggestion and preliminary code.
2008.02.14 1.8.1 added backward-compatibility for use of wikifyPlainText() in TW2.1.3 and earlier
2008.01.08 [*.*.*] plugin size reduction: documentation moved to ...Info tiddler
2007.12.28 1.8.0 added support for key="X" syntax to specify custom access key definitions
2007.12.15 1.7.0 autogenerate URI encoded HREF on links for onclick scripts. Drag links to browser toolbar to create bookmarklets. IMPORTANT NOTE: place is NOT defined when scripts are used as bookmarklets. In addition, double-quotes will cause syntax errors. Thanks to PaulReiber for debugging and brainstorming.
2007.11.26 1.6.2 when converting "document.write()" function calls in inline code, allow whitespace between "write" and "(" so that "document.write ( foobar )" is properly converted.
2007.11.16 1.6.1 when rendering "onclick scripts", pass label text through wikifyPlainText() to parse any embedded wiki-syntax to enable use of HTML entities or even TW macros to generate dynamic label text.
2007.02.19 1.6.0 added support for title="..." to specify mouseover tooltip when using an onclick (label="...") script
2006.10.16 1.5.2 add newline before closing '}' in 'function out_' wrapper. Fixes error caused when last line of script is a comment.
2006.06.01 1.5.1 when calling wikify() on script return value, pass hightlightRegExp and tiddler params so macros that rely on these values can render properly
2006.04.19 1.5.0 added 'show' parameter to force display of javascript source code in tiddler output
2006.01.05 1.4.0 added support 'onclick' scripts. When label="..." param is present, a button/link is created using the indicated label text, and the script is only executed when the button/link is clicked. 'place' value is set to match the clicked button/link element.
2005.12.13 1.3.1 when catching eval error in IE, e.description contains the error text, instead of e.toString(). Fixed error reporting so IE shows the correct response text. Based on a suggestion by UdoBorkowski
2005.11.09 1.3.0 for 'inline' scripts (i.e., not scripts loaded with src="..."), automatically replace calls to 'document.write()' with 'place.innerHTML+=' so script output is directed into tiddler content. Based on a suggestion by BradleyMeck
2005.11.08 1.2.0 handle loading of javascript from an external URL via src="..." syntax
2005.11.08 1.1.0 pass 'place' param into scripts to provide direct DOM access
2005.11.08 1.0.0 initial release
<<<
/***
|''Name:''|LoadRemoteFileThroughProxy (previous LoadRemoteFileHijack)|
|''Description:''|When the TiddlyWiki file is located on the web (view over http) the content of [[SiteProxy]] tiddler is added in front of the file url. If [[SiteProxy]] does not exist "/proxy/" is added. |
|''Version:''|1.1.0|
|''Date:''|mar 17, 2007|
|''Source:''|http://tiddlywiki.bidix.info/#LoadRemoteFileHijack|
|''Author:''|BidiX (BidiX (at) bidix (dot) info)|
|''License:''|[[BSD open source license|http://tiddlywiki.bidix.info/#%5B%5BBSD%20open%20source%20license%5D%5D ]]|
|''~CoreVersion:''|2.2.0|
***/
//{{{
version.extensions.LoadRemoteFileThroughProxy = {
major: 1, minor: 1, revision: 0,
date: new Date("mar 17, 2007"),
source: "http://tiddlywiki.bidix.info/#LoadRemoteFileThroughProxy"};
if (!window.bidix) window.bidix = {}; // bidix namespace
if (!bidix.core) bidix.core = {};
bidix.core.loadRemoteFile = loadRemoteFile;
loadRemoteFile = function(url,callback,params)
{
if ((document.location.toString().substr(0,4) == "http") && (url.substr(0,4) == "http")){
url = store.getTiddlerText("SiteProxy", "/proxy/") + url;
}
return bidix.core.loadRemoteFile(url,callback,params);
}
//}}}
/***
|Name|LoadTiddlersPlugin|
|Source|http://www.TiddlyTools.com/#LoadTiddlersPlugin|
|Documentation|http://www.TiddlyTools.com/#LoadTiddlersPluginInfo|
|Version|3.9.0|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|macro for automated updates or one-click installations of tiddlers from remote sources|
!!!!!Documentation
>see [[LoadTiddlersPluginInfo]]
!!!!!Configuration
<<<
<<option chkLoadTiddlersShowReport>>after loading tiddlers, automatically display [[ImportedTiddlers]] (if created)
__password-protected server settings //(optional, if needed)//:__
>username: <<option txtRemoteUsername>> password: <<option txtRemotePassword>>
>{{{usage: <<option txtRemoteUsername>> <<option txtRemotePassword>>}}}
>''note: these settings are also used by [[ExternalTiddlersPlugin]] and [[ImportTiddlersPlugin]]''
<<<
!!!!!Revisions
<<<
2010.08.11 3.9.0 added 'autosave' optional param
|please see [[LoadTiddlersPluginInfo]] for additional revision details|
2005.07.20 1.0.0 Initial Release
<<<
!!!!!Code
***/
//{{{
version.extensions.LoadTiddlersPlugin= {major: 3, minor: 9, revision: 0, date: new Date(2010,8,11)};
if (config.options.chkLoadTiddlersShowReport===undefined)
config.options.chkLoadTiddlersShowReport=true;
config.macros.loadTiddlers = {
label: '',
tip: "add/update tiddlers from '%0'",
lockedTag: 'noReload', // if existing tiddler has this tag value, don't overwrite it, even if inbound tiddler is newer
askMsg: 'Please enter a local path/filename or a remote URL',
openMsg: 'Opening %0',
openErrMsg: 'Could not open %0 - error=%1',
readMsg: 'Read %0 bytes from %1',
foundMsg: 'Found %0 tiddlers in %1',
nochangeMsg: "'%0' is up-to-date... skipped.",
lockedMsg: "'%0' is tagged '%1'... skipped.",
skippedMsg: 'skipped (cancelled by user)',
loadedMsg: 'Loaded %0 of %1 tiddlers from %2',
reportTitle: 'ImportedTiddlers',
warning: "Warning!! Processing '%0' as a systemConfig (plugin) tiddler may produce unexpected results! Press OK to proceed.",
autosaveMsg: 'Save current document? Press OK to proceed.',
handler: function(place,macroName,params) {
var label=(params[0] && params[0].substr(0,6)=='label:')?params.shift().substr(6):this.label;
var tip=(params[0] && params[0].substr(0,7)=='prompt:')?params.shift().substr(7):this.tip;
var filter='updates';
if (params[0] && (params[0]=='all' || params[0]=='new' || params[0]=='changes' || params[0]=='updates'
|| params[0].substr(0,8)=='tiddler:' || params[0].substr(0,4)=='tag:'))
filter=params.shift();
var src=params.shift(); if (!src || !src.length) return; // filename is required
var quiet=(params[0]=='quiet'); if (quiet) params.shift();
var ask=(params[0]=='confirm'); if (ask) params.shift();
var force=(params[0]=='force'); if (force) params.shift();
var init=(params[0]=='init'); if (init) params.shift();
var nodirty=(params[0]=='nodirty'); if (nodirty) params.shift();
var norefresh=(params[0]=='norefresh'); if (norefresh) params.shift();
var noreport=(params[0]=='noreport'); if (noreport) params.shift();
var autosave=(params[0]=='autosave'); if (autosave) params.shift();
this.newTags=[]; if (params[0]) this.newTags=params; // any remaining params are used as 'autotags'
var flags={quiet:quiet, ask:ask, filter:filter, force:force, init:init,
nodirty:nodirty, norefresh:norefresh, noreport:noreport, autosave:autosave};
if (label.trim().length) { // CLICKABLE LINK
createTiddlyButton(place,
label.format([src.replace(/%20/g,' ')]),
tip.format([src.replace(/%20/g,' ')]),
function() {
var cml=config.macros.loadTiddlers;
cml.loadFile(src,cml.doImport,flags);
return false;
})
}
else // IMMEDIATE IMPORT
this.loadFile(src,this.doImport,flags);
},
loadFile: function(src,callback,params) {
var quiet=params.quiet;
if (src=='ask') src=prompt(this.askMsg);
if (src==undefined || !src.length) return null; // filename is required
if (!quiet) clearMessage();
if (!quiet) displayMessage(this.openMsg.format([src.replace(/%20/g,' ')]));
// if working locally and src is not a URL, read from local filesystem
if (document.location.protocol=='file:' && src.substr(0,5)!='http:' && src.substr(0,5)!='file:') {
var txt=loadFile(src);
if (!txt) { // file didn't load, might be relative path.. try fixup
var pathPrefix=document.location.href; // get current document path and trim off filename
var slashpos=pathPrefix.lastIndexOf('/'); if (slashpos==-1) slashpos=pathPrefix.lastIndexOf('\\');
if (slashpos!=-1 && slashpos!=pathPrefix.length-1) pathPrefix=pathPrefix.substr(0,slashpos+1);
src=pathPrefix+src;
if (pathPrefix.substr(0,5)!='http:') src=getLocalPath(src);
var txt=loadFile(src);
}
if (!txt) { // file still didn't load, report error
if (!quiet) displayMessage(this.openErrMsg.format([src.replace(/%20/g,' '),'(unknown)']));
} else {
if (!quiet) displayMessage(this.readMsg.format([txt.length,src.replace(/%20/g,' ')]));
if (version.major+version.minor*.1+version.revision*.01!=2.52)
txt=convertUTF8ToUnicode(txt);
if (callback) callback(true,params,txt,src,null);
}
} else { // use XMLHttpRequest
doHttp('GET',src,null,null,config.options.txtRemoteUsername,config.options.txtRemotePassword,callback,params,null);
}
},
readTiddlersFromHTML: function(html) {
// for TW2.2+
if (TiddlyWiki.prototype.importTiddlyWiki!=undefined) {
var remoteStore=new TiddlyWiki();
remoteStore.importTiddlyWiki(html);
return remoteStore.getTiddlers('title');
}
},
readTiddlersFromCSV: function(CSV) {
var remoteStore=new TiddlyWiki();
// GET NAMES
var lines=CSV.replace(/\r/g,'').split('\n');
var names=lines.shift().replace(/"/g,'').split(',');
CSV=lines.join('\n');
// ENCODE commas and newlines within quoted values
var comma='!~comma~!'; var commaRE=new RegExp(comma,'g');
var newline='!~newline~!'; var newlineRE=new RegExp(newline,'g');
CSV=CSV.replace(/"([^"]*?)"/g,
function(x){ return x.replace(/\,/g,comma).replace(/\n/g,newline); });
// PARSE lines
var lines=CSV.split('\n');
for (var i=0; i<lines.length; i++) { if (!lines[i].length) continue;
var values=lines[i].split(',');
// DECODE commas, newlines, and doubled-quotes, and remove enclosing quotes (if any)
for (var v=0; v<values.length; v++)
values[v]=values[v].replace(commaRE,',').replace(newlineRE,'\n')
.replace(/^"|"$/g,'').replace(/""/g,'"');
// EXTRACT tiddler values
var title=''; var text=''; var tags=[]; var fields={};
var created=null; var when=new Date(); var who=config.options.txtUserName;
for (var v=0; v<values.length; v++) { var val=values[v];
if (names[v]) switch(names[v].toLowerCase()) {
case 'title': title=val.replace(/\[\]\|/g,'_'); break;
case 'created': created=new Date(val); break;
case 'modified':when=new Date(val); break;
case 'modifier':who=val; break;
case 'text': text=val; break;
case 'tags': tags=val.readBracketedList(); break;
default: fields[names[v].toLowerCase()]=val; break;
}
}
// CREATE tiddler in temporary store
if (title.length)
remoteStore.saveTiddler(title,title,text,who,when,tags,fields,true,created||when);
}
return remoteStore.getTiddlers('title');
},
createTiddlerFromFile: function(src,txt) {
var t=new Tiddler();
var pos=src.lastIndexOf("/"); if (pos==-1) pos=src.lastIndexOf("\\");
t.title=pos==-1?src:src.substr(pos+1);
t.text=txt;
t.created=t.modified=new Date();
t.modifier=config.options.txtUserName;
if (src.substr(src.length-3,3)=='.js') t.tags=['systemConfig'];
return [t];
},
doImport: function(status,params,html,src,xhr) {
var cml=config.macros.loadTiddlers; // abbrev
src=src.split('?')[0]; // strip off "?nocache=..."
if (!status) {
displayMessage(cml.openErrMsg.format([src.replace(/%20/g,' '),xhr.status]));
return false;
}
var quiet=params.quiet;
var ask=params.ask;
var filter=params.filter;
var force=params.force;
var init=params.init;
var nodirty=params.nodirty;
var norefresh=params.norefresh;
var noreport=params.noreport;
var autosave=params.autosave;
var tiddlers = cml.readTiddlersFromHTML(html);
if (!tiddlers||!tiddlers.length) tiddlers=cml.readTiddlersFromCSV(html);
if (!tiddlers||!tiddlers.length) tiddlers=cml.createTiddlerFromFile(src,html);
var count=tiddlers?tiddlers.length:0;
if (!quiet) displayMessage(cml.foundMsg.format([count,src.replace(/%20/g,' ')]));
var wasDirty=store.isDirty();
store.suspendNotifications();
var count=0;
if (tiddlers) for (var t=0;t<tiddlers.length;t++) {
var inbound = tiddlers[t];
var theExisting = store.getTiddler(inbound.title);
if (inbound.title==cml.reportTitle)
continue; // skip 'ImportedTiddlers' history from the other document...
if (theExisting && theExisting.tags.contains(cml.lockedTag)) {
if (!quiet) displayMessage(cml.lockedMsg.format([theExisting.title,cml.lockedTag]));
continue; // skip existing tiddler if tagged with 'noReload'
}
// apply the all/new/changes/updates filter (if any)
if (filter && filter!='all') {
if ((filter=='new') && theExisting) // skip existing tiddlers
continue;
if ((filter=='changes') && !theExisting) // skip new tiddlers
continue;
if ((filter.substr(0,4)=='tag:') && inbound.tags.indexOf(filter.substr(4))==-1) // must match specific tag value
continue;
if ((filter.substr(0,8)=='tiddler:') && inbound.title!=filter.substr(8)) // must match specific tiddler name
continue;
if (!force && store.tiddlerExists(inbound.title) && ((theExisting.modified.getTime()-inbound.modified.getTime())>=0)) {
var msg=cml.nochangeMsg;
if (!quiet&&msg.length) displayMessage(msg.format([inbound.title]));
continue;
}
}
// get confirmation if required
var msg=(theExisting?'Update':'Add')+" tiddler '"+inbound.title+"'\n"
+'from '+src.replace(/%20/g,' ')+'\n\nOK to proceed?';
if (ask && !confirm(msg))
{ tiddlers[t].status=cml.skippedMsg; continue; }
// DO IT!
var tags=new Array().concat(inbound.tags,cml.newTags);
store.saveTiddler(inbound.title, inbound.title, inbound.text, inbound.modifier,
inbound.modified, tags, inbound.fields, true, inbound.created);
// force creation date to imported value - needed for TW2.1.3 or earlier
store.fetchTiddler(inbound.title).created = inbound.created;
tiddlers[t].status=theExisting?'updated':'added'
if (init && tags.contains('systemConfig') && !tags.contains('systemConfigDisable')) {
var ok=true;
if (ask||!quiet) ok=confirm(cml.warning.format([inbound.title]))
if (ok) { // run the plugin
try { window.eval(inbound.text); tiddlers[t].status+=' (plugin initialized)'; }
catch(ex) { displayMessage(config.messages.pluginError.format([exceptionText(ex)])); }
}
}
count++;
}
store.resumeNotifications();
if (count) {
// set/clear 'unsaved changes' flag, refresh page display, and generate a report
store.setDirty(wasDirty||!nodirty);
if (!norefresh) {
story.forEachTiddler(function(t,e){
if(!story.isDirty(t))story.refreshTiddler(t,null,true)
});
store.notifyAll();
}
if (!noreport) cml.report(src,tiddlers,count,quiet);
}
if (!quiet||count) // force msg if tiddlers were loaded
displayMessage(cml.loadedMsg.format([count,tiddlers.length,src.replace(/%20/g,' ')]));
if (count && autosave && (!ask||confirm(cml.autosaveMsg))) saveChanges();
},
showReport: true,
report: function(src,tiddlers,count,quiet) {
var cml=config.macros.loadTiddlers; // abbrev
// format the new report content
var newText = 'On '+(new Date()).toLocaleString()+', ';
newText += config.options.txtUserName+' loaded '+count+' tiddlers ';
newText += 'from\n[['+src+'|'+src+']]:\n';
newText += '<<<\n';
for (var t=0; t<tiddlers.length; t++)
if (tiddlers[t].status)
newText += '#[['+tiddlers[t].title+']] - '+tiddlers[t].status+'\n';
newText += '<<<\n';
var title=cml.reportTitle;
var currText='';
var t=store.getTiddler(title);
if (t) currText=(t.text.length?'\n----\n':'')+t.text;
store.saveTiddler(title, title, newText+currText,
config.options.txtUserName, new Date(), t?t.tags:null, t?t.fields:null);
if (!quiet) {
if (config.options.chkLoadTiddlersShowReport)
story.displayTiddler(null,title);
story.refreshTiddler(title,null,true);
}
}
}
//}}}
/***
|Name|LoadTiddlersPluginInfo|
|Source|http://www.TiddlyTools.com/#LoadTiddlersPlugin|
|Documentation|http://www.TiddlyTools.com/#LoadTiddlersPluginInfo|
|Version|3.9.0|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|documentation for LoadTiddlersPlugin|
!!!!!Usage
<<<
{{{
<<loadTiddlers label:... prompt:... filter source
quiet confirm force init nodirty norefresh noreport autosave
tag tag tag...>>
}}}
*''label:...'' and ''prompt:...''<br>link and tooltip text to trigger the load tiddler processing. If a label is NOT provided, then no link is created and the loadTiddlers function is performed whenever the containing tiddler is rendered.
*''filter'' (optional keyword)<br>determines which tiddlers will be automatically selected for importing. Use one of the following:
**''all''<br>ALL tiddlers from the import source document, even if they have not been changed.
**''new''<br>only tiddlers that are found in the import source document, but do not yet exist in the destination document
**''changes''<br>only tiddlers that exist in both documents for which the import source tiddler is newer than the existing tiddler
**''updates''<br>both ''new'' and ''changes'' (this is the default action when none is specified)
**''tiddler:TiddlerName''<br>only the specified tiddler is retrieved
**''tag:value''<br>only the tiddlers tagged with the indicated value.
*''source'' (required)<br>is the location of the imported document. It can be either a local document path/filename in whatever format your system requires, or a remote web location (starting with "http://" or "https://"). Use the special keyword, ''ask'', to prompt for a source location whenever the macro is invoked
*''quiet'' (optional)<br>supresses all status message during the import processing. Note: if any tiddlers are actually imported, a final message will still be displayed, even when 'quiet' is specified. This ensures that changes to your document cannot occur without any visible indication at all.
*''confirm'' (optional)<br>adds interactive confirmation for each inbound tiddler, so that you can manually bypass any tiddlers that you do not want to import. Note: this flag also adds confirmation when using the ''autosave'' option (see below).
*''init'' (optional)<br>invokes tiddlers tagged with <<tag systemConfig>> as plugins as soon as they are imported, without requiring a save-and-reload action first. For safety, you will be asked to confirm each imported plugin, so that you can manually bypass any that you do not want to invoke. Note, however, that those tiddlers are still //imported// and saved with your document and will still take effect the next time you save-and-reload the document.
*''force'' (optional)<br>imports all matching tiddlers, even if unchanged
*''noreport'' (optional)<br>suppress generation of [[ImportedTiddlers]] report
*''nodirty'' (optional)<br>loads tiddlers without marking the document as 'dirty' (i.e., needing to be saved)
*''norefresh'' (optional)<br>prevents automatic re-rendering of the page after tiddlers are loaded
*''autosave'' (optional)<br>automatically saves the document if tiddlers have been loaded
*''tag tag tag...'' (optional)<br>any remaining parameters are used as tag values to be added to each imported tiddler (i.e., "tag-on-import")
Note: if a tiddler in the current document is tagged with<<tag noReload>> then it ''will not be overwritten, even if the inbound tiddler has been selected'' by the filtering process. This allows you to make local changes to imported tiddlers while ensuring that those changes won't be lost due to automatic tiddler updates retrieved from the import source document.
<<<
!!!!!Examples
<<<
{{{<<loadTiddlers "label:load tiddlers from %0" example.html confirm temporary>>}}}
<<loadTiddlers "label:load tiddlers from %0" example.html confirm temporary>>
{{{<<loadTiddlers "label:load tiddlers from %0 plus AUTOSAVE" example.html confirm norefresh autosave>>}}}
<<loadTiddlers "label:load tiddlers from %0" example.html confirm norefresh autosave>>
<<<
!!!!!Configuration
<<<
<<option chkLoadTiddlersShowReport>>after loading tiddlers, automatically display [[ImportedTiddlers]] (if created)
__password-protected server settings //(optional, if needed)//:__
>username: <<option txtRemoteUsername>> password: <<option txtRemotePassword>>
>{{{usage: <<option txtRemoteUsername>> <<option txtRemotePassword>>}}}
>''note: these settings are also used by [[ExternalTiddlersPlugin]] and [[ImportTiddlersPlugin]]''
<<<
!!!!!Revisions
<<<
2010.08.11 3.9.0 added 'autosave' optional param
2009.10.08 3.8.1 removed switchTheme() from doImport()... causes an INFINITE cycle of imports!
2009.10.06 3.8.0 added createTiddlerFromFile (import text files)
2009.10.04 3.7.8 in doImport(), call switchTheme() after loading tiddlers
2009.09.27 3.7.7 in readTiddlersFromCSV(), strip \r from input and fixed handling for quoted values
2009.09.01 3.7.6 added config.options.chkLoadTiddlersShowReport (default=true)
2009.09.01 3.7.6 added config.options.chkLoadTiddlersShowReport (default=true)
2009.08.30 3.7.5 in doImport(), check status and report error, if any
2009.08.29 3.7.4 in handler(), added 'return false' in button function (fixes IE page transition)
2009.08.19 3.7.3 in doImport(), fixed 'init' handling
2009.08.16 3.7.2 in doImport(), corrected check for tiddlers returned by readTiddlersFromHTML();
2009.07.03 3.7.1 fixups for TW252: doHttp() doesn't return XHR and convertUTF8ToUnicode() not needed for local I/O
2009.05.04 3.7.0 read CSV file format
2008.11.14 3.6.4 in loadFile(), force use of XMLHttpRequest if not viewing a local document (supports use of relative file references when online)
2008.10.27 3.6.3 in doImport(), fixed Safari bug by replacing static Array.concat(...) with new Array().concat(...)
2008.08.05 3.6.2 rewrote loadFile() to eliminate use of platform-specific fileExists() test
2008.08.03 3.6.1 in handler(), changed variable 'prompt' to 'tip' to avoid conflict with prompt() function
2008.01.07 3.6.0 added 'init' option to automatically invoke plugin tiddlers as soon as they are loaded (without needing save/reload)
2008.01.03 3.5.0 in loadFile(), use lower-level doHttp() instead of loadRemoteFile() in order to support username/password access to remote server
2007.12.04 *.*.* update for TW2.3.0: replaced deprecated core functions, regexps, and macros
2007.06.27 3.4.8 added missing 'fields' params to saveTiddler() call. Fixes problem where importing tiddlers would lose the custom fields.
2007.06.25 3.4.7 add calls to store.suspendNotifications() and store.resumeNotifications() to eliminate redisplay overhead DURING import activities.
2007.05.27 3.4.6 in handler(), loadRemoteFile() and doImport(), added 'noreport' flag to suppress generation of ImportedTiddlers
2007.05.27 3.4.5 in handler(), initialize 'newTags' to [] (empty array) instead of null... fixes fatal error when loading tiddler without autotagging.
2007.04.22 3.4.4 in readTiddlersFromHTML(), for TW2.2 and above, use importTiddlyWiki() (new core functionality) to get tiddlers from remote file content. Also, copied updated TW21Loader.prototype.internalizeTiddler() definition from TW2.2b5 so plugin can read tiddlers from TW2.2+ even when running under TW2.1.x
2007.04.05 3.4.3 in doImport(), changed this.readTiddlersFromHTML(html) to config.macros.loadTiddlers.readTiddlersFromHTML(html).
2007.03.26 3.4.2 renamed import() to doImport() to fix IE load-time error ("identifier expected"). "import" is a reserved word in some browsers...
2007.03.22 3.4.1 code cleanup: moved all functions inside object def'n, re-wrote report function
2007.03.21 3.4.0 split ImportTiddlersPlugin and LoadTiddlersPlugin into separate plugins
|please see [[ImportTiddlersPluginInfo]] for additional revision details|
2005.07.20 1.0.0 Initial Release
<<<
Saving notes/annotations only works on a local copy of the book.
Local copy:
*This content (one file,~5MB) can be saved locally by clicking "download" below. The content can be used offline. You will however need to be online to see the figures. When offline, the captions will be displayed without the figures.
*[[download|http://goljanpathology.tiddlyspot.com/download]]
To save annotations/notes:
* If you use a browser other than Firefox (such as Safari or Chrome), you will need to [[click here|http://www.tiddlywiki.com/TiddlySaver.jar]] and save the //~TiddlySaver.jar// file @@//to the
same folder//@@ as your main book file. (~TiddlySaver.jar is a Java applet that allows you to save changes in various browsers (Safari,Chrome) that don't support saving changes to local files.)
* You will need to agree to the various safety warnings when you try to save your annotated book file (e.g. allow //~TiddlySaver.jar// to run/load - it is digitally signed and safe)
/***
|Name|LooseLinksPlugin|
|Source|http://www.TiddlyTools.com/#LooseLinksPlugin|
|Documentation|http://www.TiddlyTools.com/#LooseLinksPlugin|
|Version|1.1.2|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|case-folded/space-folded wiki words|
!!!!!Documentation
<<<
This plugin extends the TiddlyWiki core handling for tiddler links to permit use of non-WikiWord variations of mixed-case and/or added/omitted spaces within double-bracketed text with titles of //existing// tiddlers, using a 'loose' (case-folded/space-folded) comparison. This allows text that occurs in normal prose to be more easily linked to tiddler titles by using double-brackets without the full 'pretty link' syntax. For example:
{{{
[[CoreTweaks]], [[coreTweaks]], [[core tweaks]],
[[CORE TWEAKS]], [[CoRe TwEaKs]], [[coreTWEAKS]]
}}}
>[[CoreTweaks]], [[coreTweaks]], [[core tweaks]],
>[[CORE TWEAKS]], [[CoRe TwEaKs]], [[coreTWEAKS]]
<<<
!!!!!Configuration
<<<
<<option chkLooseLinks>> Allow case-folded and/or space-folded text to link to existing tiddler titles
"""<<option chkLooseLinks>>"""
<<<
!!!!!Revisions
<<<
2009.08.14 [1.1.2] corrected call to addNotification()
2009.08.14 [1.1.1] code cleanup
2009.08.02 [1.1.0] big performance rewrite: use cached LooseLinksMap[] instead of scanning each time
2009.01.06 [1.0.0] converted to stand-alone plugin
2008.10.14 [0.0.0] initial release (as [[CoreTweaks]] #664 - http://trac.tiddlywiki.org/ticket/664)
<<<
!!!!!Code
***/
//{{{
version.extensions.LooseLinksPlugin={major:1, minor:1, revision:2, date: new Date(2009,8,15)};
if (!config.options.chkLooseLinks)
config.options.chkLooseLinks=false; // default to standard
if (window.caseFold_createTiddlyLink===undefined) { // only once
window.caseFold_createTiddlyLink = window.createTiddlyLink;
window.createTiddlyLink = function(place,title,includeText,className) {
var btn=window.caseFold_createTiddlyLink.apply(this,arguments); // create core link
if (!config.options.chkLooseLinks) return btn;
if (store.getTiddlerText(title)) return btn; // matching tiddler (or shadow) exists
var tid=window.getLooseLinksMap()[title.toLowerCase().replace(/\s/g,'')];
if (tid) {
var i=getTiddlyLinkInfo(tid,className);
btn.setAttribute('tiddlyLink',tid);
btn.title=i.subTitle;
btn.className=i.classes;
}
return btn;
}
}
window.getLooseLinksMap=function(title) {
if (!config.options.chkLooseLinks) return {}; // disable
if (!config.looseLinksMap) { // init/cache on demand
config.looseLinksMap={};
store.forEachTiddler(function(title,tiddler){
config.looseLinksMap[title.toLowerCase().replace(/\s/g,'')]=title;
});
}
if (title) config.looseLinksMap[title.toLowerCase().replace(/\s/g,'')]=title; // update
return config.looseLinksMap;
}
store.addNotification(null,window.getLooseLinksMap); // notify
//}}}
<html> </html><<tag CHAPTERS contents>> <<tag NOTES [[notes]] [[click to view list of all notes]]>> <<newEasyEdit
label:"new note"
prompt:"create a new note"
text:""
title:"new note"
focus:"title"
template:"EasyEdit+Template"
>> <<tiddler ShowPopup with: OptionsMenu [[options]] [[save/edit options]] button auto sticky>> <<tiddler ShowPopup with: Search [[search]] [[Search]] button auto sticky>> <<unsavedChanges command "There %1 %0 unsaved section%2" "view a list of unsaved changes">>
/%
the original contents button:<<tiddler ShowPopup with: ContentsMenu [[contents]] [[Open Table of Contents]] button auto sticky>>
%/
<!--{{{-->
<script> // See StorySaverPlugin for more info
if (window.coreTweaks_getParameters==undefined) {
window.coreTweaks_getParameters=window.getParameters;
window.getParameters=function() {
var p=window.coreTweaks_getParameters.apply(this,arguments);
if (!p) {
var cookies = document.cookie.split("; ");
for (var c=0; c<cookies.length; c++) {
var name=cookies[c].split("=")[0]; var value=cookies[c].split("=")[1];
if (name=="txtSavedStory" && value.length) p=unescape(value);
}
}
return p;
}
}
</script>
<!--}}}-->
<!--{{{-->
<script type="text/javascript" src="fckeditor/fckeditor.js"></script>
<!--}}}-->
<style type="text/css">#contentWrapper {display:none;}</style><div id="SplashScreen" style="border: 3px solid #ccc; display: block; text-align: center; width: 320px; margin: 100px auto; padding: 50px; color:#000; font-size: 28px; font-family:Tahoma; background-color:#eee;"><b>Rapid Review: Pathology</b> is loading<blink> ...</blink><br><br><span style="font-size: 14px; color:red;">Requires a modern browser with Javascript enabled<br>(Safari or Chrome recommended) </span></div>
/***
|Name|MatchTagsPlugin|
|Source|http://www.TiddlyTools.com/#MatchTagsPlugin|
|Documentation|http://www.TiddlyTools.com/#MatchTagsPluginInfo|
|Version|2.0.5|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|'tag matching' with full boolean expressions (AND, OR, NOT, and nested parentheses)|
!!!!!Documentation
> see [[MatchTagsPluginInfo]]
!!!!!Revisions
<<<
2011.01.23 2.0.5 fix core tweak for TW262+: adjust code in config.filters['tag'] instead of filterTiddlers()
2010.08.11 2.0.4 in getMatchingTiddlers(), fixed sorting for descending order (e.g, "-created")
| please see [[MatchTagsPluginInfo]] for additional revision details |
2008.02.28 1.0.0 initial release
<<<
!!!!!Code
***/
//{{{
version.extensions.MatchTagsPlugin= {major: 2, minor: 0, revision: 5, date: new Date(2011,23,11)};
// store.getMatchingTiddlers() processes boolean expressions for tag matching
// sortfield (optional) sets sort order for tiddlers - default=title
// tiddlers (optional) use alternative set of tiddlers (instead of current store)
TiddlyWiki.prototype.getMatchingTiddlers = function(tagexpr,sortfield,tiddlers) {
var debug=config.options.chkDebug; // abbreviation
var cmm=config.macros.matchTags; // abbreviation
var r=[]; // results are an array of tiddlers
var tids=tiddlers||store.getTiddlers();
if (tids && sortfield) tids=store.sortTiddlers(tids,sortfield);
if (debug) displayMessage(cmm.msg1.format([tids.length]));
// try simple lookup to quickly find single tags or tags that
// contain boolean operators as literals, e.g. "foo and bar"
for (var t=0; t<tids.length; t++)
if (tids[t].isTagged(tagexpr)) r.pushUnique(tids[t]);
if (r.length) {
if (debug) displayMessage(cmm.msg4.format([r.length,tagexpr]));
return r;
}
// convert expression into javascript code with regexp tests,
// so that "tag1 AND ( tag2 OR NOT tag3 )" becomes
// "/\~tag1\~/.test(...) && ( /\~tag2\~/.test(...) || ! /\~tag3\~/.test(...) )"
// normalize whitespace, tokenize operators, delimit with "~"
var c=tagexpr.trim(); // remove leading/trailing spaces
c = c.replace(/\s+/ig," "); // reduce multiple spaces to single spaces
c = c.replace(/\(\s?/ig,"~(~"); // open parens
c = c.replace(/\s?\)/ig,"~)~"); // close parens
c = c.replace(/(\s|~)?&&(\s|~)?/ig,"~&&~"); // &&
c = c.replace(/(\s|~)AND(\s|~)/ig,"~&&~"); // AND
c = c.replace(/(\s|~)?\|\|(\s|~)?/ig,"~||~"); // ||
c = c.replace(/(\s|~)OR(\s|~)/ig,"~||~"); // OR
c = c.replace(/(\s|~)?!(\s|~)?/ig,"~!~"); // !
c = c.replace(/(^|~|\s)NOT(\s|~)/ig,"~!~"); // NOT
c = c.replace(/(^|~|\s)NOT~\(/ig,"~!~("); // NOT(
// change tag terms to regexp tests
var terms=c.split("~"); for (var i=0; i<terms.length; i++) { var t=terms[i];
if (/(&&)|(\|\|)|[!\(\)]/.test(t) || t=="") continue; // skip operators/parens/spaces
if (t==config.macros.matchTags.untaggedKeyword)
terms[i]="tiddlertags=='~~'"; // 'untagged' tiddlers
else
terms[i]="/\\~"+t+"\\~/.test(tiddlertags)";
}
c=terms.join(" ");
if (debug) { displayMessage(cmm.msg2.format([tagexpr])); displayMessage(cmm.msg3.format([c])); }
// scan tiddlers for matches
for (var t=0; t<tids.length; t++) {
// assemble tags from tiddler into string "~tag1~tag2~tag3~"
var tiddlertags = "~"+tids[t].tags.join("~")+"~";
try { if(eval(c)) r.push(tids[t]); } // test tags
catch(e) { // error in test
displayMessage(cmm.msg2.format([tagexpr]));
displayMessage(cmm.msg3.format([c]));
displayMessage(e.toString());
break; // skip remaining tiddlers
}
}
if (debug) displayMessage(cmm.msg4.format([r.length,tagexpr]));
return r;
}
//}}}
//{{{
config.macros.matchTags = {
msg1: "scanning %0 input tiddlers",
msg2: "looking for '%0'",
msg3: "using expression: '%0'",
msg4: "found %0 tiddlers matching '%1'",
noMatch: "no matching tiddlers",
untaggedKeyword: "-",
untaggedLabel: "no tags",
untaggedPrompt: "show tiddlers with no tags",
defTiddler: "MatchingTiddlers",
defTags: "",
defFormat: "[[%0]]",
defSeparator: "\n",
reportHeading: "Found %0 tiddlers tagged with: '{{{%1}}}'\n----\n",
handler: function(place,macroName,params,wikifier,paramString,tiddler) {
var mode=params[0]?params[0].toLowerCase():'';
if (mode=="inline")
params.shift();
if (mode=="report" || mode=="panel") {
params.shift();
var target=params.shift()||this.defTiddler;
}
if (mode=="popup") {
params.shift();
if (params[0]&¶ms[0].substr(0,6)=="label:") var label=params.shift().substr(6);
if (params[0]&¶ms[0].substr(0,7)=="prompt:") var prompt=params.shift().substr(7);
} else {
var fmt=(params.shift()||this.defFormat).unescapeLineBreaks();
var sep=(params.shift()||this.defSeparator).unescapeLineBreaks();
}
var sortBy="+title";
if (params[0]&¶ms[0].substr(0,5)=="sort:") sortBy=params.shift().substr(5);
var expr = params.join(" ");
if (mode!="panel" && (!expr||!expr.trim().length)) return;
if (expr==this.untaggedKeyword)
{ var label=this.untaggedLabel; var prompt=this.untaggedPrompt };
switch (mode) {
case "popup": this.createPopup(place,label,expr,prompt,sortBy); break;
case "panel": this.createPanel(place,expr,fmt,sep,sortBy,target); break;
case "report": this.createReport(target,this.defTags,expr,fmt,sep,sortBy); break;
case "inline": default: this.createInline(place,expr,fmt,sep,sortBy); break;
}
},
formatList: function(tids,fmt,sep) {
var out=[];
for (var i=0; i<tids.length; i++) { var t=tids[i];
var title=t.title;
var who=t.modifier;
var when=t.modified.toLocaleString();
var text=t.text;
var first=t.text.split("\n")[0];
var desc=store.getTiddlerSlice(t.title,"description");
desc=desc||store.getTiddlerSlice(t.title,"Description");
desc=desc||store.getTiddlerText(t.title+"##description");
desc=desc||store.getTiddlerText(t.title+"##Description");
var tags=t.tags.length?'[['+t.tags.join(']] [[')+']]':'';
out.push(fmt.format([title,who,when,text,first,desc,tags]));
}
return out.join(sep);
},
createInline: function(place,expr,fmt,sep,sortBy) {
wikify(this.formatList(store.sortTiddlers(store.getMatchingTiddlers(expr),sortBy),fmt,sep),place);
},
createPopup: function(place,label,expr,prompt,sortBy) {
var btn=createTiddlyButton(place,
(label||expr).format([expr]),
(prompt||config.views.wikified.tag.tooltip).format([expr]),
function(ev){ return config.macros.matchTags.showPopup(this,ev||window.event); });
btn.setAttribute("sortBy",sortBy);
btn.setAttribute("expr",expr);
},
showPopup: function(here,ev) {
var p=Popup.create(here); if (!p) return false;
var tids=store.getMatchingTiddlers(here.getAttribute("expr"));
store.sortTiddlers(tids,here.getAttribute("sortBy"));
var list=[]; for (var t=0; t<tids.length; t++) list.push(tids[t].title);
if (!list.length) createTiddlyText(p,this.noMatch);
else {
var b=createTiddlyButton(createTiddlyElement(p,"li"),
config.views.wikified.tag.openAllText,
config.views.wikified.tag.openAllTooltip,
function() {
var list=this.getAttribute("list").readBracketedList();
story.displayTiddlers(null,tids);
});
b.setAttribute("list","[["+list.join("]] [[")+"]]");
createTiddlyElement(p,"hr");
}
var out=this.formatList(tids," [[%0]] ","\n"); wikify(out,p);
Popup.show();
ev.cancelBubble=true;
if(ev.stopPropagation) ev.stopPropagation();
return false;
},
createReport: function(target,tags,expr,fmt,sep,sortBy) {
var tids=store.sortTiddlers(store.getMatchingTiddlers(expr),sortBy);
if (!tids.length) { displayMessage('no matches for: '+expr); return false; }
var msg=config.messages.overwriteWarning.format([target]);
if (store.tiddlerExists(target) && !confirm(msg)) return false;
var out=this.reportHeading.format([tids.length,expr])
out+=this.formatList(tids,fmt,sep);
store.saveTiddler(target,target,out,config.options.txtUserName,new Date(),tags,{});
story.closeTiddler(target); story.displayTiddler(null,target);
},
createPanel: function(place,expr,fmt,sep,sortBy,tid) {
var s=createTiddlyElement(place,"span"); s.innerHTML=store.getTiddlerText("MatchTagsPlugin##html");
var f=s.getElementsByTagName("form")[0];
f.expr.value=expr; f.fmt.value=fmt; f.sep.value=sep.escapeLineBreaks();
f.tid.value=tid; f.tags.value=this.defTags;
}
};
//}}}
/***
//{{{
!html
<form style='display:inline;white-space:nowrap'>
<input type='text' name='expr' style='width:50%' title='tag expression'><!--
--><input type='text' name='fmt' style='width:10%' title='list item format'><!--
--><input type='text' name='sep' style='width:5%' title='list item separator'><!--
--><input type='text' name='tid' style='width:12%' title='target tiddler title'><!--
--><input type='text' name='tags' style='width:10%' title='target tiddler tags'><!--
--><input type='button' name='go' style='width:8%' value='go' onclick="
var expr=this.form.expr.value;
if (!expr.length) { alert('Enter a boolean tag expression'); return false; }
var fmt=this.form.fmt.value;
if (!fmt.length) { alert('Enter the list item output format'); return false; }
var sep=this.form.sep.value.unescapeLineBreaks();
var tid=this.form.tid.value;
if (!tid.length) { alert('Enter a target tiddler title'); return false; }
var tags=this.form.tags.value;
config.macros.matchTags.createReport(tid,tags,expr,fmt,sep,'title');
return false;">
</form>
!end
//}}}
***/
//{{{
// SHADOW TIDDLER for displaying default panel input form
config.shadowTiddlers.MatchTags="<<matchTags panel>>";
//}}}
//{{{
// TWEAK core filterTiddlers() or config.filters['tag'] (in TW262+)
// to use getMatchingTiddlers instead getTaggedTiddlers
// for enhanced boolean matching in [tag[...]] syntax
var TW262=config.filters && config.filters['tag']; // detect TW262+
var fname=TW262?"config.filters['tag']":"TiddlyWiki.prototype.filterTiddlers";
var code=eval(fname).toString().replace(/getTaggedTiddlers/g,'getMatchingTiddlers');
eval(fname+'='+code);
//}}}
//{{{
// REDEFINE core handler for enhanced boolean matching in tag:"..." paramifier
// use filterTiddlers() instead of getTaggedTiddlers() to get list of tiddlers.
config.paramifiers.tag = {
onstart: function(v) {
var tagged = store.filterTiddlers("[tag["+v+"]]");
story.displayTiddlers(null,tagged,null,false,null);
}
};
//}}}
/***
|Name|MatchTagsPluginInfo|
|Source|http://www.TiddlyTools.com/#MatchTagsPlugin|
|Documentation|http://www.TiddlyTools.com/#MatchTagsPluginInfo|
|Version|2.0.5|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|documentation for MatchTagsPlugin|
!!!!!Usage
<<<
This plugin extends the {{{[tag[tagname]]}}} macro parameter syntax used by the TiddlyWiki core {{{<<list>>}}} macro so that, instead of a simple tagname value, you can specify a complex combination of tagname values using a //boolean expression// containing AND, OR, and NOT operators, enclosed in nested parentheses if needed.
{{{
<<list filter "[tag[expression]]">>
}}}
In addition, the plugin defines a new macro, {{{<<matchTags ...>>}}} that can be used instead of the core {{{<<list>>}}} macro to output a list of matching tiddlers //using a custom 'item format' and 'separator'//. You can also use this macro to create a command link that displays the matching tiddlers within a popup list, similar to the standard {{{<<tag tagName>>}}} macro, but matching a combination of tag values rather than a single tag value.
{{{
<<matchTags inline "format" "separator" sort:fieldname tag expression>>
<<matchTags popup "label:..." "prompt:..." sort:fieldname tag expression>>
<<matchTags report TiddlerName "format" "separator" sort:fieldname tag expression>>
<<matchTags panel Tiddlername "format" "separator" sort:fieldname tag expression>>
}}}
where:
* ''inline'', ''report'', ''panel'', and ''popup''<br>are keywords that indicate the type of output that the macro should produce:
** ''inline'' //(default)// - displays a list of matching tiddlers embedded directly in tiddler content
** ''popup'' - embeds a command button that, when clicked, lists matching tiddlers in a ~TiddlyWiki popup display
** ''report'' - generates a list of matching tiddler in a separate [[MatchingTiddlers]] report tiddler
** ''panel'' - displays an interactive form for generating a [[MatchingTiddlers]] report
* ''format''<br>defines the wiki-syntax for rendering list items. The following //substitution markers// can be used to insert tiddler-specific information for each matched tiddler:
** {{{%0}}} - title
** {{{%1}}} - modifier (author)
** {{{%2}}} - modified (date of last change)
** {{{%3}}} - text (all tiddler content)
** {{{%4}}} - firstline (tiddler content up to the first newline)
** {{{%5}}} - description (tiddler slice or section content named "description" or "Description")
** {{{%6}}} - tags (space-separated, bracketed list)
* ''separator''<br>defines the wiki-syntax to use //between// each matching title (e.g., ", " creates a comma-separated list, while "\n" displays one tiddler per line).
* ''sort:fieldname'' (optional)<br>specifies the sort order for the resulting list of tiddlers. You can specify any tiddler field name (standard or custom-defined). Standard tiddler fieldnames include: //title, created, modified, modifier//. If not specified, tiddlers are sorted by title. You can prefix the fieldname with "+" or "-" to indicate ascending or descending order, respectively.
* ''tag expression''<br>the remaining parameter(s) are joined together to define the boolean expression to be matched.
When using the ''popup'' option, there are two additional (and optional) parameters you can specify:
* ''"label:..."''(optional)<br> indicates the text for the popup command link. The default is to display the specified tag expression itself.
* ''"prompt:..."'' (optional)<br>indicates the mouseover 'tooltip' for the popup command link.
When using the ''report'' or ''panel'' option, an additional parameter may be provided:
* ''~TiddlerName''<br>specifies the target tiddler into which the output will be generated (default: [[MatchingTiddlers]])
Notes:
*A tag expression can use any combination of text operators: ''AND'', ''OR'', ''NOT'' (or their equivalent javascript operators: ''&&'', ''||'', ''!''), contained in nested parentheses as needed.
*Operators should be delimited by spaces or parentheses.
*Before matching, leading/trailing spaces are automatically trimmed and multiple spaces are reduced to single spaces.
*Tag values containing embedded spaces do //not// have to be enclosed in {{{[[...]]}}}.
*Tag values that contain boolean operators as ''literal text'' (e.g., {{{"foo and bar"}}} or {{{"foo && bar"}}} cannot be used within a compound boolean expression, but //can// be matched if specified by themselves, without any other tag values or operators.
*To match tiddlers that are untagged, use "-" as a special tag value within the expression.
*You can match "wildcard" tags by using //regular expression// (i.e., "text pattern") syntax within a tag value, e.g. {{{[Tt]agvalue.*}}}
<<<
!!!!!Examples:
<<<
display a popup list:
{{{
<<matchTags popup sample OR (settings AND systemConfig)>>
}}}
><<matchTags popup sample OR (settings AND systemConfig)>>
display a popup list with custom label:
{{{
<<matchTags popup "label:samples and settings" sample OR (settings AND systemConfig)>>
}}}
><<matchTags popup "label:samples and settings" sample OR (settings AND systemConfig)>>
display a popup list of untagged tiddlers:
{{{
<<matchTags popup ->>
}}}
><<matchTags popup ->>
generate a report using interactive form control panel
{{{
<<matchTags panel "MatchingTiddlers" "[[%0]]" "\n" sample OR (settings AND systemConfig)>>
}}}
>{{smallform{<<matchTags panel "MatchingTiddlers" "[[%0]]" "\n" sample OR (settings AND systemConfig)>>}}}
comma-separated list:
{{{
<<matchTags "[[%0]]" ", " sample OR (settings AND systemConfig)>>
}}}
><<matchTags "[[%0]]" ", " sample OR (settings AND systemConfig)>>
numbered list (sorted by modification date, most recent first):
{{{
<<matchTags "#[[%0]] (%2)<br>^^%5^^" "\n" sort:-modified sample OR (settings AND systemConfig)>>
}}}
><<matchTags "#[[%0]] (%2)<br>^^%5^^" "\n" sort:-modified sample OR (settings AND systemConfig)>>
bullet-item list (using the TiddlyWiki core {{{<<list filter ...>>}}} macro):
//(Note: when using the core {{{<<list>>}}} macro, you should always enclose the entire tag filter parameter within quotes)//
{{{
<<list filter "[tag[sample OR (settings AND systemConfig)]]">>
}}}
><<list filter "[tag[sample OR (settings AND systemConfig)]]">>
<<<
!!!!!Revisions
<<<
2011.01.22 2.0.5 fix core tweak for TW262+: adjust code in config.filters['tag'] instead of filterTiddlers()
2010.08.11 2.0.4 in getMatchingTiddlers(), fixed sorting for descending order (e.g, "-created")
2010.03.02 2.0.3 added %6 format (tags)
2010.03.01 2.0.2 in formatList(), don't automatically put '[[' and ']]' around title (%0) in formatted output
2009.08.29 2.0.1 added support for {{{config.macros.matchTags.defTags}}} to auto-tag [[MatchingTiddlers]] output
2008.09.04 2.0.0 added "report" and "panel" options to generate formatted results and store in a tiddler. Also, added config.macros.matchTags.formatList(place,fmt,sep) API to return formatted output for use with other plugins/scripts
2008.09.01 1.9.2 fixed return value from popup button handler so IE doesn't attempt to leave the page
2008.08.31 1.9.1 improved expression conversion handling to permit use of regular expressions for "wildcard" matching within tag values
2008.06.12 1.9.0 added support for formatted output of: title, who, when, text, firstline, description (slice or section)
2008.06.05 1.8.0 in getMatchingTiddlers(), added optional sortfield and tiddlers params to support use of alternative set of tiddlers instead of using current store content (provides filtering support for ImportTiddlersPlugin)
2008.06.04 1.7.1 in getMatchingTiddlers(), reworked conversion of expression for more robust parsing of whitespace, parentheses and javascript operators and allow use of "-" (untagged) //within// expressions
2008.05.19 1.7.0 in getMatchingTiddlers(), use reverseLookup() instead of forEachTiddler() to permit access to tiddlers included via [[IncludePlugin|http://tiddlywiki.abego-software.de/#IncludePlugin]]
2008.05.17 1.6.0 in getMatchingTiddlers(), rewrote expression conversion to handle tags with spaces tag values that are substrings of other tag values.
2008.05.16 1.5.0 added special case using "-" to find UNTAGGED tiddlers
2008.05.15 1.4.0 added "popup" output option
2008.05.14 1.3.4 instead of hijacking getTaggedTiddlers(), added tweak of filterTiddlers() prototype to replace getTaggedTiddlers() with getMatchingTiddler() so that core use of getTaggedTiddlers() does not perform boolean processing of tiddler titles such as [[To Be or not To Be]]. Also, improved "filter error" messages in getMatchingTiddlers() to report tag expression in addition to actual eval error.
2008.04.25 1.3.3 in getTaggedTiddlers(), fixed handling for "not" embedded within a tag
2008.04.21 1.3.2 in getTaggedTiddlers(), fixed handling for initial "NOT" and "NOT(expr)" syntax
2008.04.20 1.3.1 in getTaggedTiddlers(), corrected check for boolean expression to avoid excess processing of tags containing spaces. Also, improved handling for non-existing tags that contain text of existing tags
2008.04.19 1.3.0 in filterTiddlers(), use getTaggedTiddlers() instead of matchTags(), and then hijack getTaggedTiddlers() to add matchTags() handling
2008.04.19 [*.*.*] plugin size reduction: moved documentation to [[MatchTagsPluginInfo]]
2008.03.25 1.2.0 added optional "sort:fieldname" parameter
2008.03.20 1.1.2 in handler(), replace 'encodeTiddlyLink' with explicit [[...]] brackets to ensure that one-word tiddler titles are properly rendered as TiddlyLinks
2008.02.29 1.1.1 in matchTags(), added handling to skip remaining tiddlers if expression has an error
2008.02.29 1.1.0 refactored to define store.matchTags() and extend store.filterTiddlers()
2008.02.28 1.0.0 initial release
<<<
/%
!info
|Name|NextTiddler|
|Source|http://www.TiddlyTools.com/#NextTiddler|
|Version|2.0.0|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|transclusion|
|Description|create a link to close the current tiddler and open another in its place|
Usage:
<<<
{{{
<<tiddler NextTiddler with: NextTiddlerTitle linktext>>
}}}
<<<
Example
<<<
{{{<<tiddler NextTiddler with: About "About TiddlyTools">>}}}
<<tiddler NextTiddler with: About "About TiddlyTools">>
<<<
!end
!show
[[$2|$1]]<<tiddler {{
place.lastChild.onclick=function() {
var here=story.findContainingTiddler(this);
story.displayTiddler(here,"$1"); // open next
//story.closeTiddler(here.getAttribute('tiddler')); // close self
}
'';}}>>
!end
%/<<tiddler {{'NextTiddler##'+('$1'=='$'+'1'?'info':'show')}} with: [[$1]] [[$2]]>>
/%
!info
|Name|OpenTiddlers|
|Source|http://www.TiddlyTools.com/#OpenTiddlers|
|Version|2.0.0|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|transclusion|
|Description|command link to open multiple tiddlers with a single click|
Usage:
<<<
in tiddler content:
{{{
<<tiddler OpenTiddlers with: label
"tiddler tiddler [[tiddler with spaces]] tiddler..." template>>
}}}
note: ''template'' is optional and defaults to ViewTemplate
<<<
!end
!show
<html><nowiki><a href='javascript:;' onclick='
var tidlist="$2";
if ("$3"!="$"+"3") var template="$3";
story.displayTiddlers(story.findContainingTiddler(place),tidlist.readBracketedList(),template);
return false;
'>$1</a></html>
!end
%/<<tiddler {{'OpenTiddlers##'+("$1"=='$'+'1'?'info':'show')}}
with: [[$1]] {{"$2"}} [[$3]]>>
@@color:darkGray;text-align:justify;{{buttonBlock{<<saveChanges "save changes" "save the book file">>}}}
save backup? <<option chkSaveBackups>>
----
<script>
editModeButtonCallback=function(rootel){
config.options.chkEditMode=!config.options.chkEditMode;
place.innerHTML=config.options.chkEditMode? 'edit mode •' : 'edit mode';
jQuery(rootel).click();
story.refreshAllTiddlers();
}
rootel=Popup.stack[0].root;
createTiddlyButton(place,(config.options.chkEditMode? 'edit mode •' : 'edit mode'),'enable/disable edit mode',function(){editModeButtonCallback(rootel)});
</script>
----
/%username for signing your notes and annotated book sections:%/username:
<<option txtUserName>>
----
<<permaview>>/%Permanent link to open sections. Bookmark appears in address bar%/
----
font size: <<fontSize>>
----
[[Local copy]]
[[Tips]]
[[More information|Information]]
[[Annotating]]
<!--{{{-->
<span style="display:none;" macro="tiddler ToggleRightSidebar with: '.'"></span>
<div style="z-index:4500;position:relative;">
<div class='header' macro="gradient vert #18f #04b">
<span class='siteTitle' refresh='content' tiddler='SiteTitle'></span>
<span class='siteSubtitle' refresh='content' tiddler='SiteSubtitle'></span>
</div>
<div class='topMenu'>
<div style="display:inline" refresh='content' tiddler='MainMenu'></div>
<div style="display:inline;float:right;" refresh='content' tiddler="SubMenu"></div>
</div>
</div>
<div id="fixedMenu" class='topMenu' style="z-index:4499;position:fixed; top:0px; width:100%;">
<div style="display:inline" refresh='content' tiddler='MainMenu'></div>
<div style="display:inline;float:right;" refresh='content' tiddler="SubMenu"></div>
</div>
<div id='sidebar'>
<!-- <div id='sidebarOptions' refresh='content' tiddler='SideBarOptions'></div> -->
<div id='sidebarTabs' refresh='content' force='true' tiddler='SideBarTabs'></div>
</div>
<div id='displayArea'>
<div id='messageArea'></div>
<div id='tiddlerDisplay'></div>
</div>
<!--}}}-->
/***
|''Name''|PaletteViewMacro|
|''Version''|0.2|
|''Author''|FND|
|''Source''|[[FND's DevPad|http://devpad.tiddlyspot.com/#PaletteViewMacro]]|
|''License''|[[Creative Commons Attribution-ShareAlike 3.0 License|http://creativecommons.org/licenses/by-sa/3.0/]]|
|''~CoreVersion''|2.1|
|''Type''|macro|
|''Requires''|N/A|
|''Overrides''|N/A|
|''Description''|Displays color palettes.|
!Notes
There is also [[ViewPalettePlugin|http://simon.tiddlyspot.com/#ViewPalettePlugin]], which currently does not work with TiddlyWiki v2.2 though.
!Usage
{{{
<<paletteView [tiddler name]>>
}}}
!!Example
<<paletteView [[ColorPalette]]>>
!Revision History
!!v0.1 (2007-11-18)
* initial release
!!v0.2 (2007-11-20)
* limited processing to slices containing [[actual color values|http://www.w3.org/TR/CSS21/syndata.html#color-units]]
* changed fallback value to the tiddler the macro is called from (instead of using [[ColorPalette]])
!To Do
* selection list for all available palettes (tag-based)
* parameter for custom table class
* customizable column order
* documentation (e.g. using from within [[ViewTemplate]])
!Code
***/
//{{{
config.macros.paletteView = {};
config.macros.paletteView.handler = function(place, macroName, params, wikifier, paramString, tiddler) {
var title = params[0] || tiddler.title;
//var palettes = store.getTaggedTiddlers(params[0]); // DEBUG: yet to be implemented
var colors = store.calcAllSlices(title);
var labels = [];
for(var c in colors) {
if(this.isColor(colors[c])) {
labels.push(c);
}
}
if(labels.length > 0) {
var output = "|!Sample|!Value|!Name|h\n";
for(var i = 0; i < labels.length; i++) {
output += "|padding:0 4em;background-color:" + colors[labels[i]] + "; |"
+ "{{{" + colors[labels[i]] + "}}}|"
+ "[[" + labels[i] + "|" + title + "]]|\n";
}
wikify(output, place);
}
};
config.macros.paletteView.isColor = function(s) {
var colors = ["Black", "Green", "Silver", "Lime", "Gray", "Olive", "White", "Yellow",
"Maroon", "Navy", "Red", "Blue", "Purple", "Teal", "Fuchsia", "Aqua", "Orange"];
var match = s.match(/^#[0-9A-F]{3}$|^#[0-9A-F]{6}$|^RGB\([\d,\s]{5,}\)$/i);
if(match) return true;
if(colors.contains(s)) return true;
return false;
};
//}}}
/***
|''Name:''|PasswordOptionPlugin|
|''Description:''|Extends TiddlyWiki options with non encrypted password option.|
|''Version:''|1.0.2|
|''Date:''|Apr 19, 2007|
|''Source:''|http://tiddlywiki.bidix.info/#PasswordOptionPlugin|
|''Author:''|BidiX (BidiX (at) bidix (dot) info)|
|''License:''|[[BSD open source license|http://tiddlywiki.bidix.info/#%5B%5BBSD%20open%20source%20license%5D%5D ]]|
|''~CoreVersion:''|2.2.0 (Beta 5)|
***/
//{{{
version.extensions.PasswordOptionPlugin = {
major: 1, minor: 0, revision: 2,
date: new Date("Apr 19, 2007"),
source: 'http://tiddlywiki.bidix.info/#PasswordOptionPlugin',
author: 'BidiX (BidiX (at) bidix (dot) info',
license: '[[BSD open source license|http://tiddlywiki.bidix.info/#%5B%5BBSD%20open%20source%20license%5D%5D]]',
coreVersion: '2.2.0 (Beta 5)'
};
config.macros.option.passwordCheckboxLabel = "Save this password on this computer";
config.macros.option.passwordInputType = "password"; // password | text
setStylesheet(".pasOptionInput {width: 11em;}\n","passwordInputTypeStyle");
merge(config.macros.option.types, {
'pas': {
elementType: "input",
valueField: "value",
eventName: "onkeyup",
className: "pasOptionInput",
typeValue: config.macros.option.passwordInputType,
create: function(place,type,opt,className,desc) {
// password field
config.macros.option.genericCreate(place,'pas',opt,className,desc);
// checkbox linked with this password "save this password on this computer"
config.macros.option.genericCreate(place,'chk','chk'+opt,className,desc);
// text savePasswordCheckboxLabel
place.appendChild(document.createTextNode(config.macros.option.passwordCheckboxLabel));
},
onChange: config.macros.option.genericOnChange
}
});
merge(config.optionHandlers['chk'], {
get: function(name) {
// is there an option linked with this chk ?
var opt = name.substr(3);
if (config.options[opt])
saveOptionCookie(opt);
return config.options[name] ? "true" : "false";
}
});
merge(config.optionHandlers, {
'pas': {
get: function(name) {
if (config.options["chk"+name]) {
return encodeCookie(config.options[name].toString());
} else {
return "";
}
},
set: function(name,value) {config.options[name] = decodeCookie(value);}
}
});
// need to reload options to load passwordOptions
loadOptionsCookie();
/*
if (!config.options['pasPassword'])
config.options['pasPassword'] = '';
merge(config.optionsDesc,{
pasPassword: "Test password"
});
*/
//}}}
/%
!info
|Name|QuickSearchPopup|
|Source|http://www.TiddlyTools.com/#QuickSearchPopup|
|Version|2.0.0|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|transclusion|
|Requires|SearchOptionsPlugin, StickyPopupPlugin|
|Description|popup list of tiddlers containing text matching specified text or current tiddler title|
Usage
<<<
{{{
<<tiddler QuickSearchPopup>>
<<tiddler QuickSearchPopup with: "searchtext" "label">>
}}}
*''searchtext'' (optional, default=current tiddler title)
*''label'' (optional) text for popup command link
*''tip'' (optional) tooltip for popup command link
<<<
Example
<<<
{{{<<tiddler QuickSearchPopup with: {{tiddler.title}} "click me">>}}}
<<tiddler QuickSearchPopup##show with: {{tiddler.title}} "click me">>
<<<
!end
!show
<html><nowiki><a href="javascript:;" title="$3"
onmouseover="var t='$1';
this.title=t.length?('list tiddlers containing text: \''+t+'\''):'disabled: no text to match';
"
onclick="var t='$1'; if (!t.length) return;
var p=Popup.create(this); if (!p) return;
addClass(p,'sticky');
var d=createTiddlyElement(p,'div');
d.style.whiteSpace='normal';
d.style.width='auto';
d.style.padding='2px';
wikify('\<\<search [['+t+']] report=summary+list [[$2\n----\n]]\>\>',d);
Popup.show();
event.cancelBubble = true;
if (event.stopPropagation) event.stopPropagation();
return(false);
">$2</a></html>
!end
%/<<tiddler {{var src='QuickSearchPopup'; src+(tiddler&&tiddler.title==src?'##info':'##show')}}
with: {{'$1'!='$'+'1'?'$1':(story.findContainingTiddler(place)||place).getAttribute('tiddler')||'';}}
{{'$2'!='$'+'2'?'$2':'see also'}}
{{'$3'!='$'+'3'?'$3':'list tiddlers containing matching text'}}
>>
/***
|Name|RearrangeTiddlersPlugin|
|Source|http://www.TiddlyTools.com/#RearrangeTiddlersPlugin|
|Version|2.0.0|
|Author|Eric Shulman|
|OriginalAuthor|Joe Raii|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|drag tiddlers by title to re-order story column display|
adapted from: http://www.cs.utexas.edu/~joeraii/dragn/#Draggable
changes by ELS:
* hijack refreshTiddler() instead of overridding createTiddler()
* find title element by className instead of elementID
* set cursor style via code instead of stylesheet
* set tooltip help text
* set tiddler "position:relative" when starting drag event, restore saved value when drag ends
* update 2006.08.07: use getElementsByTagName("*") to find title element, even when it is 'buried' deep in tiddler DOM elements (due to custom template usage)
* update 2007.03.01: use apply() to invoke hijacked core function
* update 2008.01.13: only hijack core function once. (allows for dynamic loading of plugin via bookmarklet)
* update 2008.10.19: added onclick popup menu with 'move to top' and 'move to bottom' commands
* update 2010.11.30: use story.getTiddler()
***/
//{{{
if (Story.prototype.rearrangeTiddlersHijack_refreshTiddler===undefined) {
Story.prototype.rearrangeTiddlersHijack_refreshTiddler = Story.prototype.refreshTiddler;
Story.prototype.refreshTiddler = function(title,template)
{
this.rearrangeTiddlersHijack_refreshTiddler.apply(this,arguments);
var theTiddler = this.getTiddler(title); if (!theTiddler) return;
var theHandle;
var children=theTiddler.getElementsByTagName("*");
for (var i=0; i<children.length; i++) if (hasClass(children[i],"title")) { theHandle=children[i]; break; }
if (!theHandle) return theTiddler;
Drag.init(theHandle, theTiddler, 0, 0, null, null);
theHandle.style.cursor="move";
theHandle.title="drag title to re-arrange tiddlers, click for more options..."
theTiddler.onDrag = function(x,y,myElem) {
if (this.style.position!="relative")
{ this.savedstyle=this.style.position; this.style.position="relative"; }
y = myElem.offsetTop;
var next = myElem.nextSibling;
var prev = myElem.previousSibling;
if (next && y + myElem.offsetHeight > next.offsetTop + next.offsetHeight/2) {
myElem.parentNode.removeChild(myElem);
next.parentNode.insertBefore(myElem, next.nextSibling);//elems[pos+1]);
myElem.style["top"] = -next.offsetHeight/2+"px";
}
if (prev && y < prev.offsetTop + prev.offsetHeight/2) {
myElem.parentNode.removeChild(myElem);
prev.parentNode.insertBefore(myElem, prev);
myElem.style["top"] = prev.offsetHeight/2+"px";
}
};
theTiddler.onDragEnd = function(x,y,myElem) {
myElem.style["top"] = "0px";
if (this.savedstyle!=undefined)
this.style.position=this.savedstyle;
};
theHandle.onclick=function(ev) {
ev=ev||window.event;
var p=Popup.create(this); if (!p) return;
var b=createTiddlyButton(createTiddlyElement(p,"li"),
"\u25B2 move to top of column ","move this tiddler to the top of the story column",
function() {
var t=story.getTiddler(this.getAttribute("tid"));
t.parentNode.insertBefore(t,t.parentNode.firstChild); // move to top of column
window.scrollTo(0,ensureVisible(t));
return false;
});
b.setAttribute("tid",title);
var b=createTiddlyButton(createTiddlyElement(p,"li"),
"\u25BC move to bottom of column ","move this tiddler to the bottom of the story column",
function() {
var t=story.getTiddler(this.getAttribute("tid"));
t.parentNode.insertBefore(t,null); // move to bottom of column
window.scrollTo(0,ensureVisible(t));
return false;
});
b.setAttribute("tid",title);
Popup.show();
ev.cancelBubble=true; if (ev.stopPropagation) ev.stopPropagation(); return(false);
};
return theTiddler;
}
}
/**************************************************
* dom-drag.js
* 09.25.2001
* www.youngpup.net
**************************************************
* 10.28.2001 - fixed minor bug where events
* sometimes fired off the handle, not the root.
**************************************************/
var Drag = {
obj:null,
init:
function(o, oRoot, minX, maxX, minY, maxY) {
o.onmousedown = Drag.start;
o.root = oRoot && oRoot != null ? oRoot : o ;
if (isNaN(parseInt(o.root.style.left))) o.root.style.left="0px";
if (isNaN(parseInt(o.root.style.top))) o.root.style.top="0px";
o.minX = typeof minX != 'undefined' ? minX : null;
o.minY = typeof minY != 'undefined' ? minY : null;
o.maxX = typeof maxX != 'undefined' ? maxX : null;
o.maxY = typeof maxY != 'undefined' ? maxY : null;
o.root.onDragStart = new Function();
o.root.onDragEnd = new Function();
o.root.onDrag = new Function();
},
start:
function(e) {
var o = Drag.obj = this;
e = Drag.fixE(e);
var y = parseInt(o.root.style.top);
var x = parseInt(o.root.style.left);
o.root.onDragStart(x, y, Drag.obj.root);
o.lastMouseX = e.clientX;
o.lastMouseY = e.clientY;
if (o.minX != null) o.minMouseX = e.clientX - x + o.minX;
if (o.maxX != null) o.maxMouseX = o.minMouseX + o.maxX - o.minX;
if (o.minY != null) o.minMouseY = e.clientY - y + o.minY;
if (o.maxY != null) o.maxMouseY = o.minMouseY + o.maxY - o.minY;
document.onmousemove = Drag.drag;
document.onmouseup = Drag.end;
Drag.obj.root.style["z-index"] = "10";
return false;
},
drag:
function(e) {
e = Drag.fixE(e);
var o = Drag.obj;
var ey = e.clientY;
var ex = e.clientX;
var y = parseInt(o.root.style.top);
var x = parseInt(o.root.style.left);
var nx, ny;
if (o.minX != null) ex = Math.max(ex, o.minMouseX);
if (o.maxX != null) ex = Math.min(ex, o.maxMouseX);
if (o.minY != null) ey = Math.max(ey, o.minMouseY);
if (o.maxY != null) ey = Math.min(ey, o.maxMouseY);
nx = x + (ex - o.lastMouseX);
ny = y + (ey - o.lastMouseY);
Drag.obj.root.style["left"] = nx + "px";
Drag.obj.root.style["top"] = ny + "px";
Drag.obj.lastMouseX = ex;
Drag.obj.lastMouseY = ey;
Drag.obj.root.onDrag(nx, ny, Drag.obj.root);
return false;
},
end:
function() {
document.onmousemove = null;
document.onmouseup = null;
Drag.obj.root.style["z-index"] = "0";
Drag.obj.root.onDragEnd(parseInt(Drag.obj.root.style["left"]), parseInt(Drag.obj.root.style["top"]), Drag.obj.root);
Drag.obj = null;
},
fixE:
function(e) {
if (typeof e == 'undefined') e = window.event;
if (typeof e.layerX == 'undefined') e.layerX = e.offsetX;
if (typeof e.layerY == 'undefined') e.layerY = e.offsetY;
return e;
}
};
//}}}
<<search>> <<option chkSearchTitles>>titles <<option chkSearchText>>text /%<<option chkSearchOpenTiddlers>>only in open sections%/
/***
|Name|SearchOptionsPlugin|
|Source|http://www.TiddlyTools.com/#SearchOptionsPlugin|
|Documentation|http://www.TiddlyTools.com/#SearchOptionsPluginInfo|
|Version|3.0.7|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|extend core search function with additional user-configurable options|
Adds extra options to core search function including selecting which data items to search, enabling/disabling incremental key-by-key searches, and generating a ''list of matching tiddlers'' instead of immediately displaying all matches. This plugin also adds syntax for rendering 'search links' within tiddler content to embed one-click searches using pre-defined 'hard-coded' search terms.
!!!!!Documentation
>see [[SearchOptionsPluginInfo]]
!!!!!Configuration
<<<
Search in:
<<option chkSearchTitles>> titles <<option chkSearchText>> text <<option chkSearchTags>> tags <<option chkSearchFields>> fields <<option chkSearchShadows>> shadows
<<option chkSearchHighlight>> Highlight matching text in displayed tiddlers
<<option chkSearchList>> Show list of matches
<<option chkSearchListTiddler>> Write list to [[SearchResults]] tiddler
<<option chkSearchTitlesFirst>> Show title matches first
<<option chkSearchByDate>> Sort matching tiddlers by modification date (most recent first)
<<option chkSearchResultsOptions>> Include {{{options...}}} slider in "search again" form
<<option chkIncrementalSearch>> Incremental key-by-key search: {{twochar{<<option txtIncrementalSearchMin>>}}} or more characters, {{threechar{<<option txtIncrementalSearchDelay>>}}} msec delay
<<option chkSearchOpenTiddlers>> Search only in tiddlers that are currently displayed
<<option chkSearchExcludeTags>> Exclude tiddlers tagged with: <<option txtSearchExcludeTags>>
<<<
!!!!!Revisions
<<<
2010.05.03 3.0.8 added chkSearchResultsOptions to allow/omit the "options..." slider from the "search again" form
|please see [[SearchOptionsPluginInfo]] for additional revision details|
2005.10.18 1.0.0 Initial Release
<<<
!!!!!Code
***/
//{{{
version.extensions.SearchOptionsPlugin= {major: 3, minor: 0, revision: 8, date: new Date(2010,5,3)};
var defaults={
chkSearchTitles: true,
chkSearchText: true,
chkSearchTags: true,
chkSearchFields: true,
chkSearchTitlesFirst: true,
chkSearchList: true,
chkSearchHighlight: true,
chkSearchListTiddler: false,
chkSearchByDate: false,
chkIncrementalSearch: true,
chkSearchShadows: true,
chkSearchOpenTiddlers: false,
chkSearchResultsOptions:true,
chkSearchExcludeTags: true,
txtSearchExcludeTags: 'excludeSearch',
txtIncrementalSearchDelay: 500,
txtIncrementalSearchMin: 3
}; for (var id in defaults) if (config.options[id]===undefined)
config.options[id]=defaults[id];
if (config.macros.search.reportTitle==undefined)
config.macros.search.reportTitle="SearchResults"; // note: not a cookie!
config.macros.search.label+="\xa0"; // a little bit of space just because it looks better
//}}}
// // searchLink: {{{[search[text to find]] OR [search[text to display|text to find]]}}}
//{{{
config.formatters.push( {
name: "searchLink",
match: "\\[search\\[",
lookaheadRegExp: /\[search\[(.*?)(?:\|(.*?))?\]\]/mg,
prompt: "search for: '%0'",
handler: function(w)
{
this.lookaheadRegExp.lastIndex = w.matchStart;
var lookaheadMatch = this.lookaheadRegExp.exec(w.source);
if(lookaheadMatch && lookaheadMatch.index == w.matchStart) {
var label=lookaheadMatch[1];
var text=lookaheadMatch[2]||label;
var prompt=this.prompt.format([text]);
var btn=createTiddlyButton(w.output,label,prompt,
function(){story.search(this.getAttribute("searchText"))},"searchLink");
btn.setAttribute("searchText",text);
w.nextMatch = this.lookaheadRegExp.lastIndex;
}
}
});
//}}}
// // incremental search uses option settings instead of hard-coded delay and minimum input values
//{{{
var fn=config.macros.search.onKeyPress;
fn=fn.toString().replace(/500/g, "config.options.txtIncrementalSearchDelay||500");
fn=fn.toString().replace(/> 2/g, ">=(config.options.txtIncrementalSearchMin||3)");
eval("config.macros.search.onKeyPress="+fn);
//}}}
// // REPLACE story.search() for option to "show search results in a list"
//{{{
Story.prototype.search = function(text,useCaseSensitive,useRegExp)
{
var co=config.options; // abbrev
var re=new RegExp(useRegExp ? text : text.escapeRegExp(),useCaseSensitive ? "mg" : "img");
if (config.options.chkSearchHighlight) highlightHack=re;
var matches = store.search(re,co.chkSearchByDate?"modified":"title","");
if (co.chkSearchByDate) matches=matches.reverse(); // most recent first
var q = useRegExp ? "/" : "'";
clearMessage();
if (!matches.length) {
if (co.chkSearchListTiddler) discardSearchResults();
displayMessage(config.macros.search.failureMsg.format([q+text+q]));
} else {
if (co.chkSearchList||co.chkSearchListTiddler)
reportSearchResults(text,matches);
else {
var titles = []; for(var t=0; t<matches.length; t++) titles.push(matches[t].title);
this.closeAllTiddlers(); story.displayTiddlers(null,titles);
displayMessage(config.macros.search.successMsg.format([matches.length, q+text+q]));
}
}
highlightHack = null;
}
//}}}
// // REPLACE store.search() for enhanced searching/sorting options
//{{{
TiddlyWiki.prototype.search = function(searchRegExp,sortField,excludeTag,match)
{
var co=config.options; // abbrev
var tids = this.reverseLookup("tags",excludeTag,!!match,sortField);
var opened=[]; story.forEachTiddler(function(tid,elem){opened.push(tid);});
// eliminate tiddlers tagged with excluded tags
if (co.chkSearchExcludeTags&&co.txtSearchExcludeTags.length) {
var ex=co.txtSearchExcludeTags.readBracketedList();
var temp=[]; for(var t=tids.length-1; t>=0; t--)
if (!tids[t].tags.containsAny(ex)) temp.push(tids[t]);
tids=temp;
}
// scan for matching titles first...
var results = [];
if (co.chkSearchTitles) {
for(var t=0; t<tids.length; t++) {
if (co.chkSearchOpenTiddlers && !opened.contains(tids[t].title)) continue;
if(tids[t].title.search(searchRegExp)!=-1) results.push(tids[t]);
}
if (co.chkSearchShadows)
for (var t in config.shadowTiddlers) {
if (co.chkSearchOpenTiddlers && !opened.contains(t)) continue;
if ((t.search(searchRegExp)!=-1) && !store.tiddlerExists(t))
results.push((new Tiddler()).assign(t,config.shadowTiddlers[t]));
}
}
// then scan for matching text, tags, or field data
for(var t=0; t<tids.length; t++) {
if (co.chkSearchOpenTiddlers && !opened.contains(tids[t].title)) continue;
if (co.chkSearchText && tids[t].text.search(searchRegExp)!=-1)
results.pushUnique(tids[t]);
if (co.chkSearchTags && tids[t].tags.join(" ").search(searchRegExp)!=-1)
results.pushUnique(tids[t]);
if (co.chkSearchFields && store.forEachField!=undefined)
store.forEachField(tids[t],
function(tid,field,val) {
if (val.search(searchRegExp)!=-1) results.pushUnique(tids[t]);
},
true); // extended fields only
}
// then check for matching text in shadows
if (co.chkSearchShadows)
for (var t in config.shadowTiddlers) {
if (co.chkSearchOpenTiddlers && !opened.contains(t)) continue;
if ((config.shadowTiddlers[t].search(searchRegExp)!=-1) && !store.tiddlerExists(t))
results.pushUnique((new Tiddler()).assign(t,config.shadowTiddlers[t]));
}
// if not 'titles first', or sorting by modification date,
// re-sort results to so titles, text, tag and field matches are mixed together
if(!sortField) sortField = "title";
var bySortField=function(a,b){
if(a[sortField]==b[sortField])return(0);else return(a[sortField]<b[sortField])?-1:+1;
}
if (!co.chkSearchTitlesFirst || co.chkSearchByDate) results.sort(bySortField);
return results;
}
//}}}
// // HIJACK core {{{<<search>>}}} macro to add "report" and "simple inline" output
//{{{
config.macros.search.SOP_handler=config.macros.search.handler;
config.macros.search.handler = function(place,macroName,params)
{
// if "report", use SearchOptionsPlugin report generator for inline output
if (params[1]&¶ms[1].substr(0,6)=="report") {
var keyword=params[0];
var options=params[1].split("=")[1]; // split "report=option+option+..."
var heading=params[2]?params[2].unescapeLineBreaks():"";
var matches=store.search(new RegExp(keyword.escapeRegExp(),"img"),"title","excludeSearch");
if (matches.length) wikify(heading+window.formatSearchResults(keyword,matches,options),place);
} else if (params[1]) {
var keyword=params[0];
var heading=params[1]?params[1].unescapeLineBreaks():"";
var seperator=params[2]?params[2].unescapeLineBreaks():", ";
var matches=store.search(new RegExp(keyword.escapeRegExp(),"img"),"title","excludeSearch");
if (matches.length) {
var out=[];
for (var m=0; m<matches.length; m++) out.push("[["+matches[m].title+"]]");
wikify(heading+out.join(seperator),place);
}
} else
config.macros.search.SOP_handler.apply(this,arguments);
};
//}}}
// // SearchResults panel handling
//{{{
setStylesheet(".searchResults { padding:1em 1em 0 1em; }","searchResults"); // matches std tiddler padding
config.macros.search.createPanel=function(text,matches,body) {
function getByClass(e,c) { var d=e.getElementsByTagName("div");
for (var i=0;i<d.length;i++) if (hasClass(d[i],c)) return d[i]; }
var panel=createTiddlyElement(null,"div","searchPanel","searchPanel");
this.renderPanel(panel,text,matches,body);
var oldpanel=document.getElementById("searchPanel");
if (!oldpanel) { // insert new panel just above tiddlers
var da=document.getElementById("displayArea");
da.insertBefore(panel,da.firstChild);
} else { // if panel exists
var oldwrap=getByClass(oldpanel,"searchResults");
var newwrap=getByClass(panel,"searchResults");
// if no prior content, just insert new content
if (!oldwrap) oldpanel.insertBefore(newwrap,null);
else { // swap search results content but leave containing panel intact
oldwrap.style.display='block'; // unfold wrapper if needed
var i=oldwrap.getElementsByTagName("input")[0]; // get input field
if (i) { var pos=this.getCursorPos(i); i.onblur=null; } // get cursor pos, ignore blur
oldpanel.replaceChild(newwrap,oldwrap);
panel=oldpanel; // use existing panel
}
}
this.showPanel(true,pos);
return panel;
}
config.macros.search.renderPanel=function(panel,text,matches,body) {
var wrap=createTiddlyElement(panel,"div",null,"searchResults");
wrap.onmouseover = function(e){ addClass(this,"selected"); }
wrap.onmouseout = function(e){ removeClass(this,"selected"); }
// create toolbar: "open all", "fold/unfold", "close"
var tb=createTiddlyElement(wrap,"div",null,"toolbar");
var b=createTiddlyButton(tb, "open all", "open all matching tiddlers", function() {
story.displayTiddlers(null,this.getAttribute("list").readBracketedList()); return false; },"button");
var list=""; for(var t=0;t<matches.length;t++) list+='[['+matches[t].title+']] ';
b.setAttribute("list",list);
var b=createTiddlyButton(tb, "fold", "toggle display of search results", function() {
config.macros.search.foldPanel(this); return false; },"button");
var b=createTiddlyButton(tb, "close", "dismiss search results", function() {
config.macros.search.showPanel(false); return false; },"button");
createTiddlyText(createTiddlyElement(wrap,"div",null,"title"),"Search for: "+text); // title
wikify(body,createTiddlyElement(wrap,"div",null,"viewer")); // report
return panel;
}
config.macros.search.showPanel=function(show,pos) {
var panel=document.getElementById("searchPanel");
var i=panel.getElementsByTagName("input")[0];
i.onfocus=show?function(){config.macros.search.stayFocused(true);}:null;
i.onblur=show?function(){config.macros.search.stayFocused(false);}:null;
if (show && panel.style.display=="block") { // if shown, grab focus, restore cursor
if (i&&this.stayFocused()) { i.focus(); this.setCursorPos(i,pos); }
return;
}
if(!config.options.chkAnimate) {
panel.style.display=show?"block":"none";
if (!show) { removeChildren(panel); config.macros.search.stayFocused(false); }
} else {
var s=new Slider(panel,show,false,show?"none":"children");
s.callback=function(e,p){e.style.overflow="visible";}
anim.startAnimating(s);
}
return panel;
}
config.macros.search.foldPanel=function(button) {
var d=document.getElementById("searchPanel").getElementsByTagName("div");
for (var i=0;i<d.length;i++) if (hasClass(d[i],"viewer")) var v=d[i]; if (!v) return;
var show=v.style.display=="none";
if(!config.options.chkAnimate)
v.style.display=show?"block":"none";
else {
var s=new Slider(v,show,false,"none");
s.callback=function(e,p){e.style.overflow="visible";}
anim.startAnimating(s);
}
button.innerHTML=show?"fold":"unfold";
return false;
}
config.macros.search.stayFocused=function(keep) { // TRUE/FALSE=set value, no args=get value
if (keep===undefined) return this.keepReportInFocus;
this.keepReportInFocus=keep;
return keep
}
config.macros.search.getCursorPos=function(i) {
var s=0; var e=0; if (!i) return { start:s, end:e };
try {
if (i.setSelectionRange) // FF
{ s=i.selectionStart; e=i.selectionEnd; }
if (document.selection && document.selection.createRange) { // IE
var r=document.selection.createRange().duplicate();
var len=r.text.length; s=0-r.moveStart('character',-100000); e=s+len;
}
}catch(e){};
return { start:s, end:e };
}
config.macros.search.setCursorPos=function(i,pos) {
if (!i||!pos) return; var s=pos.start; var e=pos.end;
if (i.setSelectionRange) //FF
i.setSelectionRange(s,e);
if (i.createTextRange) // IE
{ var r=i.createTextRange(); r.collapse(true); r.moveStart("character",s); r.select(); }
}
//}}}
// // SearchResults report generation
// note: these functions are defined globally, so they can be more easily redefined to customize report formats//
//{{{
if (!window.reportSearchResults) window.reportSearchResults=function(text,matches)
{
var cms=config.macros.search; // abbrev
var body=window.formatSearchResults(text,matches);
if (!config.options.chkSearchListTiddler) // show #searchResults panel
window.scrollTo(0,ensureVisible(cms.createPanel(text,matches,body)));
else { // write [[SearchResults]] tiddler
var title=cms.reportTitle;
var who=config.options.txtUserName;
var when=new Date();
var tags="excludeLists excludeSearch temporary";
var tid=store.getTiddler(title); if (!tid) tid=new Tiddler();
tid.set(title,body,who,when,tags);
store.addTiddler(tid);
story.closeTiddler(title);
story.displayTiddler(null,title);
}
}
if (!window.formatSearchResults) window.formatSearchResults=function(text,matches,opt)
{
var body='';
var title=config.macros.search.reportTitle
var q = config.options.chkRegExpSearch ? "/" : "'";
if (!opt) var opt="all";
var parts=opt.split("+");
for (var i=0; i<parts.length; i++) { var p=parts[i].toLowerCase();
if (p=="again"||p=="all") body+=window.formatSearchResults_again(text,matches);
if (p=="summary"||p=="all") body+=window.formatSearchResults_summary(text,matches);
if (p=="list"||p=="all") body+=window.formatSearchResults_list(text,matches);
if (p=="buttons"||p=="all") body+=window.formatSearchResults_buttons(text,matches);
}
return body;
}
if (!window.formatSearchResults_again) window.formatSearchResults_again=function(text,matches)
{
var title=config.macros.search.reportTitle
var body='';
// search again
body+='{{span{<<search "'+text.replace(/"/g,'"')+'">> /%\n';
body+='%/<html><input type="button" value="search again"';
body+=' onclick="var t=this.parentNode.parentNode.getElementsByTagName(\'input\')[0];';
body+=' config.macros.search.doSearch(t); return false;">';
if (!config.options.chkSearchResultsOptions) { // omit "options..."
body+='</html>}}}\n\n';
return body;
}
body+=' <a href="javascript:;" onclick="';
body+=' var e=this.parentNode.nextSibling;';
body+=' var show=e.style.display!=\'block\';';
body+=' if(!config.options.chkAnimate) e.style.display=show?\'block\':\'none\';';
body+=' else anim.startAnimating(new Slider(e,show,false,\'none\'));';
body+=' return false;">options...</a>';
body+='</html>@@display:none;border-left:1px dotted;margin-left:1em;padding:0;padding-left:.5em;font-size:90%;/%\n';
body+=' %/<<option chkSearchTitles>>titles /%\n';
body+=' %/<<option chkSearchText>>text /%\n';
body+=' %/<<option chkSearchTags>>tags /%\n';
body+=' %/<<option chkSearchFields>>fields /%\n';
body+=' %/<<option chkSearchShadows>>shadows\n';
body+=' <<option chkCaseSensitiveSearch>>case-sensitive /%\n';
body+=' %/<<option chkRegExpSearch>>text patterns /%\n';
body+=' %/<<option chkSearchByDate>>sorted by date\n';
body+=' <<option chkSearchHighlight>> highlight matching text in displayed tiddlers\n';
body+=' <<option chkIncrementalSearch>>incremental key-by-key search: /%\n';
body+=' %/{{twochar{<<option txtIncrementalSearchMin>>}}} or more characters, /%\n';
body+=' %/{{threechar{<<option txtIncrementalSearchDelay>>}}} msec delay\n';
body+=' <<option chkSearchOpenTiddlers>> search only in tiddlers that are currently displayed\n';
body+=' <<option chkSearchExcludeTags>>exclude tiddlers tagged with:\n';
body+=' {{editor{<<option txtSearchExcludeTags>>}}}/%\n';
body+='%/@@}}}\n\n';
return body;
}
if (!window.formatSearchResults_summary) window.formatSearchResults_summary=function(text,matches)
{
// summary: nn tiddlers found matching '...', options used
var body='';
var co=config.options; // abbrev
var title=config.macros.search.reportTitle
var q = co.chkRegExpSearch ? "/" : "'";
body+="''"+config.macros.search.successMsg.format([matches.length,q+"{{{"+text+"}}}"+q])+"''\n";
var opts=[];
if (co.chkSearchTitles) opts.push("titles");
if (co.chkSearchText) opts.push("text");
if (co.chkSearchTags) opts.push("tags");
if (co.chkSearchFields) opts.push("fields");
if (co.chkSearchShadows) opts.push("shadows");
if (co.chkSearchOpenTiddlers) body+="^^//search limited to displayed tiddlers only//^^\n";
body+="~~ searched in "+opts.join(" + ")+"~~\n";
body+=(co.chkCaseSensitiveSearch||co.chkRegExpSearch?"^^ using ":"")
+(co.chkCaseSensitiveSearch?"case-sensitive ":"")
+(co.chkRegExpSearch?"pattern ":"")
+(co.chkCaseSensitiveSearch||co.chkRegExpSearch?"matching^^\n":"");
return body;
}
if (!window.formatSearchResults_list) window.formatSearchResults_list=function(text,matches)
{
// bullet list of links to matching tiddlers
var body='';
var co=config.options; // abbrev
var pattern=co.chkRegExpSearch?text:text.escapeRegExp();
var sensitive=co.chkCaseSensitiveSearch?"mg":"img";
var link='{{tiddlyLinkExisting{<html><nowiki><a href="javascript:;" onclick="'
+'if(config.options.chkSearchHighlight)'
+' highlightHack=new RegExp(\x27'+pattern+'\x27.escapeRegExp(),\x27'+sensitive+'\x27);'
+'story.displayTiddler(null,\x27%0\x27);'
+'highlightHack = null; return false;'
+'" title="%2">%1</a></html>}}}';
for(var t=0;t<matches.length;t++) {
body+="* ";
if (co.chkSearchByDate)
body+=matches[t].modified.formatString('YYYY.0MM.0DD 0hh:0mm')+" ";
var title=matches[t].title;
var fixup=title.replace(/'/g,"\\x27").replace(/"/g,"\\x22");
var tid=store.getTiddler(title);
var tip=tid?tid.getSubtitle():''; tip=tip.replace(/"/g,""");
body+=link.format([fixup,title,tip])+'\n';
}
return body;
}
if (!window.formatSearchResults_buttons) window.formatSearchResults_buttons=function(text,matches)
{
// embed buttons only if writing SearchResults to tiddler
if (!config.options.chkSearchListTiddler) return "";
// "open all" button
var title=config.macros.search.reportTitle;
var body="";
body+="@@diplay:block;<html><input type=\"button\" href=\"javascript:;\" "
+"onclick=\"story.displayTiddlers(null,[";
for(var t=0;t<matches.length;t++)
body+="'"+matches[t].title.replace(/\'/mg,"\\'")+"'"+((t<matches.length-1)?", ":"");
body+="],1);\" accesskey=\"O\" value=\"open all matching tiddlers\"></html> ";
// "discard SearchResults" button
body+="<html><input type=\"button\" href=\"javascript:;\" "
+"onclick=\"discardSearchResults()\" value=\"discard "+title+"\"></html>";
body+="@@\n";
return body;
}
if (!window.discardSearchResults) window.discardSearchResults=function()
{
// remove the tiddler
story.closeTiddler(config.macros.search.reportTitle);
store.deleteTiddler(config.macros.search.reportTitle);
store.notify(config.macros.search.reportTitle,true);
}
//}}}
/***
|Name|SearchOptionsPluginInfo|
|Source|http://www.TiddlyTools.com/#SearchOptionsPlugin|
|Documentation|http://www.TiddlyTools.com/#SearchOptionsPluginInfo|
|Version|3.0.8|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|Documentation for SearchOptionsPlugin|
Extend core search function with additional user-configurable options including selecting which data items to search, enabling/disabling incremental key-by-key searches, and generating a ''list of matching tiddler'' instead of immediately displaying all matches. This plugin also adds syntax for rendering 'search links' within tiddler content to embed one-click searches using pre-defined 'hard-coded' search terms.
!!!!!Search link Syntax
<<<
To insert a 'search link' into tiddler content, you can write:
{{{
[search[text to find]]
}}}
or
{{{
[search[text to display|text to find]]
}}}
Clicking on the resulting search link will trigger the search functionality, just as if the specified 'text to find' had been entered into the standard search input field usually displayed in the document sidebar.
<<<
!!!!!Inline output: search macro syntax
<<<
Alternatively, to embed search results lists directly into your tiddler content, you can use:
{{{
<<search "text" report>> (report is a literal keyword)
<<search "text" "heading" "separator">> (simple inline generator)
}}}
<<<
!!!!!Inline output examples:
<<<
*+++*[<<search "wood">>]>...
<<search "wood">>
===
*+++*[<<search "wood" "/%%/">>]>...
<<search "wood" "/%%/">>
===
*+++*[<<search "wood" "See also: ">>]>...
<<search "wood" "See also: ">>
===
*+++*[<<search "wood" "See also:\n*" "\n*">>]>...
<<search "wood" "See also:\n*" "\n*">>
===
*+++*[<<search "wood" report=list "See also:">>]>...
<<search "wood" report=list "See Also:" >>
===
*+++*[<<search "wood" report>>]>...
<<search "wood" report>>
===
*+++*[<<search "wood" report=>>]>...
<<search "wood" report=>>
===
*+++*[<<search "wood" report=all>>]>...
<<search "wood" report=all>>
===
*+++*[<<search "wood" report=summary+buttons+again+list>>]>...
<<search "wood" report=summary+buttons+again+list>>
===
*+++*[<<search "wood" report=summary+again>>]>...
<<search "wood" report=summary+again>>
===
*+++*[<<search "wood" report=summary>>]>...
<<search "wood" report=summary>>
===
<<<
!!!!!Configuration
<<<
Search in:
<<option chkSearchTitles>> titles <<option chkSearchText>> text <<option chkSearchTags>> tags <<option chkSearchFields>> fields <<option chkSearchShadows>> shadows
{{{<<option chkSearchTitles>> <<option chkSearchText>> <<option chkSearchTags>>}}}
{{{<<option chkSearchFields>> <<option chkSearchShadows>>}}}
<<option chkSearchHighlight>> Highlight matching text in displayed tiddlers {{{<<option chkSearchHighlight>>}}}
<<option chkSearchList>> Show list of matches {{{<<option chkSearchList>>}}}
<<option chkSearchListTiddler>> Write list to [[SearchResults]] tiddler {{{<<option chkSearchListTiddler>>}}}
<<option chkSearchTitlesFirst>> Show title matches first {{{<<option chkSearchTitlesFirst>>}}}
<<option chkSearchByDate>> Sort matching tiddlers by date {{{<<option chkSearchByDate>>}}}
<<option chkSearchResultsOptions>> Include {{{options...}}} slider in "search again" form
<<option chkIncrementalSearch>> Incremental key-by-key search: {{twochar{<<option txtIncrementalSearchMin>>}}} or more characters, {{threechar{<<option txtIncrementalSearchDelay>>}}} msec delay
{{{<<option chkSearchIncremental>> <<option txtSearchIncrementalMin>> <<option txtSearchIncrementalDelay>>}}}
<<option chkSearchOpenTiddlers>> Search only in tiddlers that are currently displayed {{{<<option chkSearchOpenTiddlers>>}}}
<<option chkSearchExcludeTags>> Exclude tiddlers tagged with: <<option txtSearchExcludeTags>>
{{{<<option chkSearchExcludeTags>>}}} {{{<<option txtSearchExcludeTags>>}}}
<<<
!!!!!Revisions
<<<
2010.05.03 3.0.8 added chkSearchResultsOptions to allow/omit the "options..." slider from the "search again" form
2010.02.25 3.0.7 in formatSearchResults_list, added declaration of local 'co' variable
2009.09.22 3.0.6 in TiddlyWiki.prototype.search, added 'match' param for core compatibility
2009.01.16 3.0.5 added chkSearchOpenTiddlers option to limit searches to displayed tiddlers only
2009.01.15 3.0.4 in formatSearchResults_list(), corrected link generation to properly handle single-quotes and double-quotes in tiddler titles
2009.01.09 3.0.3 added chkSearchHighlight to optionally disable highlighting of matched text
2009.01.05 3.0.2 in formatSearchResults_list(), set/clear 'highlightHack' via HTML links so that search term will be highlighted when displaying tiddlers.
2008.10.14 3.0.1 changed panel class from "tiddler" to "searchPanel" and added style definition for "searchPanel". Fixes ticket #771 (in IE, links from search results were reporting errors due to "fake" tiddler class wrapper)
2008.10.02 3.0.0 added optional list of tags to use for excluding tiddler from searches (default="excludeLists").
2008.09.24 2.9.9 performance improvment to reportSearchResults(): when rendering a real SearchResults tiddler, store.notify() isn't needed since the results tiddler is always explicitly closed and redrawn each time.
2008.09.20 2.9.8 corrected createPanel() and renderPanel() so toolbar will be correctly shown/hidden on mouseover/mouseout.
2008.09.19 2.9.7 fixes to panel handling for IE, Safari, and others. Changed panel id to #searchPanel and added .searchResults CSS class wrapper around panel content. Fixed fold/unfold handling.
2008.09.18 2.9.6 refactored panel handling code, added 'fold/unfold' panel toolbar command, added dynamic 'title' (shows search term), added txtIncrementalSearchMin option
2008.09.17 2.9.5 added focus and cursor handling for 'search again' field in #searchResults DIV report so that an incremental key-by-key search doesn't interfere with continuous typing into the field.
2008.09.17 2.9.4 fix 'flicker' when updating #searchResults DIV by wikify()ing to an 'offscreen' DIV and then using replaceChild() instead of using removeChildren() followed by wikify()
2008.09.16 2.9.3 changed report layout, added "search again" and collapsible 'options' section with incremental search checkbox and "txtIncrementalSearchDelay" timer tweak to onKeyPress()
2008.08.25 2.9.2 added animation to search results DIV. Also, the #searchResults DOM element is only auto-created if it does not exist ... and when closed, the DIV is simply hidden rather than removed. This allows custom placement of search results report in the PageTemplate definition.
2008.08.23 2.9.1 story column search results uses {{{<<moveablePanel>>}}}
2008.08.22 2.9.0 default is now to show search results at top of story column, similar to FND's SimpleSearchPlugin display, with an option to generate SearchResults tiddler as before. Also changed 'chkSearchIncremental' to 'chkIncrementalSearch' to match core option variable
2008.08.12 2.8.2 change default for chkSearchByDate back to FALSE, and adjusted "list" and "again" output formats (minor tweaks requested by PhilWhitehouse for use on TiddlyWiki.com)
2008.08.11 2.8.1 changed defaults for chkSearchTitlesFirst, chkSearchList and chkSearchShadows to TRUE to enable enhanced search results output as soon as plugin is installed.
2008.06.21 2.8.0 added extended syntax for {{{<<search "text" report heading>> and <<search "text" "heading" "seperator">>}}}
2008.05.03 2.7.1 in searchLink formatter handler(), use separate setAttribute() call instead of passing attribs to createTiddlyButton(). Avoids conflict with errant code in TiddlerNotesPlugin (v2.1 26/10/07)
2008.04.29 2.7.0 added searchLink formatter (syntax: {{{[search[text]]}}} or {{{[search[display|text]]}}})
2008.04.08 2.6.2 don't automatically add options to AdvancedOptions shadow tiddler
2007.02.17 2.6.1 added redefinition of config.macros.search.onKeyPress() to restore check to bypass key-by-key searching (i.e., when chkSearchIncremental==false), which had been unintentionally removed with v2.6.0
2007.02.13 2.6.0 remove redefinition of config.macros.search.handler since core now includes handling for ENTER key.
2007.02.08 2.5.1 include 'temporary' tag when creating SearchResults (for use with TemporaryTiddlersPlugin)
2007.01.29 2.5.0 added support for "sort results by date". Default is to sort alphabetically (standard). When sorted by dates, most recent changes are shown first
2006.10.10 2.4.0 added support for "search in tiddler data" (tiddler.fields) Default is to search extended data.
2006.04.06 2.3.0 added support for "search in shadow tiddlers". Default is *not* to search in the shadows (i.e. standard TW behavior). Note: if a shadow tiddler has a 'real' counterpart, only the real tiddler is searched, since the shadow is inaccessible for viewing/editing.
2006.02.03 2.2.1 rewrite timeout clearing code and blank search text handling to match 2.0.4 core release changes. note that core no longer permits "blank=all" searches, so neither does this plugin. To search for all, use "." with text patterns enabled.
2006.02.02 2.2.0 in search.handler(), KeyHandler() function clears 'left over' timeout when search input is < 3 chars. Prevents searching on shorter text when shortened by rapid backspaces (<500msec)
2006.02.01 2.1.9 in Story.prototype.search(), correct inverted logic for using/not using regular expressions when searching
also, blank search text now presents "No search text. Continue anyway?" confirm() message box, so search on blank can still be processed if desired by user.
2006.02.01 2.1.8 in doSearch(), added alert/return if search text is blank
2006.01.20 2.1.7 fixed setting of config.macros.search.reportTitle so that Tweaks can override it.
2006.01.19 2.1.6 improved SearchResults formatting, added a "search again" form to the report (based on a suggestion from MorrisGray)
define results report title using config.macros.search.reportTitle instead of hard-coding the tiddler title
2006.01.18 2.1.5 Created separate functions for reportSearchResults(text,matches) and discardSearchResults(), so that other developers can create alternative report generators.
2006.01.17 2.1.4 Use regExp.search() instead of regExp.test() to scan for matches. Correctd the problem where only half the matching tiddlers (the odd-numbered ones) were being reported.
2006.01.15 2.1.3 Added information (date/time, username, search options used) to SearchResults output
2006.01.10 2.1.2 use displayTiddlers() to render matched tiddlers. This lets you display multiple matching tiddlers, even if SinglePageModePlugin is enabled.
2006.01.08 2.1.1 corrected invalid variable reference, "txt.value" to "text" in story.search()
2006.01.08 2.1.0 re-write to match new store.search(), store.search.handler() and story.search() functions.
2005.12.30 2.0.0 Upgraded to TW2.0. When rendering SearchResults tiddler, closeTiddler() first to ensure display is refreshed.
2005.12.26 1.4.0 added option to search for matching text in tiddler tags
2005.12.21 1.3.7 use \\ to 'escape' single quotes in tiddler titles when generating "Open all matching tiddlers" link. Also, added access key: "O", to trigger "open all" link. Based on a suggestion by UdoBorkowski.
2005.12.18 1.3.6 call displayMessage() AFTER showing matching tiddlers so message is not cleared too soon
2005.12.17 1.3.5 if no matches found, just display message and delete any existing SearchResults tiddler.
2005.12.17 1.3.4 use {/%%/{/%%/{ and }/%%/}/%%/} to 'escape' display text in SearchResults tiddler to ensure that formatting contained in search string is not rendered. Based on a suggestion by UdoBorkowski.
2005.12.14 1.3.3 tag SearchResults tiddler with 'excludeSearch' so it won't list itself in subsequent searches. Based on a suggestion by UdoBorkowski.
2005.12.14 1.3.2 added "open all matching tiddlers..." link to search results output. Based on a suggestion by UdoBorkowski.
2005.12.10 1.3.1 added "discard search results" link to end of search list tiddler output for quick self-removal of 'SearchResults' tiddler.
2005.12.01 1.3.0 added chkSearchIncremental to enable/disable 'incremental' searching (i.e., search after each keystroke) (default is ENABLED).
added handling for Enter key so it can be used to start a search. Based on a suggestion by LyallPearce
2005.11.25 1.2.1 renamed from SearchTitleOrTextPlugin to SearchOptionsPlugin
2005.11.25 1.2.0 added chkSearchList option. Based on a suggestion by RodneyGomes
2005.10.19 1.1.0 added chkSearchTitlesFirst option. Based on a suggestion by ChristianHauck
2005.10.18 1.0.0 Initial Release. Based on a suggestion by LyallPearce.
<<<
/%
!info
|Name|ShowPopup|
|Source|http://www.TiddlyTools.com/#ShowPopup|
|Version|1.2.0|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|transclusion|
|Description|display tiddler content in a TiddlyWiki popup panel|
Usage:
<<<
{{{
<<tiddler ShowPopup with: TiddlerName label tooltip buttonClass width popupClass>>
}}}
where:
*''~TiddlerName''<br>title of the tiddler to be displayed
*''label''<br>text for the command link
*''tooltip''<br>mouseover help text for the link
*''buttonClass''<br>CSS classname applied to the command text (default=button)
*''width''<br>width of the popup (using CSS measurements, default=auto)
*''popupClass''<br>CSS classname applied to the popup panel (default=none).<br>Use 'sticky' for persistent popups (see StickyPopupPlugin)
<<<
Example:
<<<
{{{
<<tiddler ShowPopup with: ShowPopup [[Try this]] [[show this tiddler in a popup]]>>
}}}
<<tiddler ShowPopup with: ShowPopup [[Try this]] [[show this tiddler in a popup]]>>
<<<
!end
!show
<html><hide linebreaks>
<a href="javascript:;" class="$4" title="$3" onclick="
var p=Popup.create(this); if(!p)return;
p.className+='$6'!='$'+'6'?' $6':'';
var d=createTiddlyElement(p,'div');
var s=d.style;
s.whiteSpace='normal';
s.width='$5'!='$'+'5'?'$5':'auto';
s.padding='2px';
wikify(store.getTiddlerText('$1',''),d);
Popup.show();
event.cancelBubble=true;
if(event.stopPropagation)event.stopPropagation();
return(false);
">$2</a></html>
!end
%/<<tiddler {{'ShowPopup##'+('$1'=='$'+'1'?'info':'show')}} with: [[$1]] [[$2]] [[$3]] [[$4]] [[$5]] [[$6]]>>
/***
|Name|SinglePageModePluginInfo|
|Source|http://www.TiddlyTools.com/#SinglePageModePlugin|
|Documentation|http://www.TiddlyTools.com/#SinglePageModePluginInfo|
|Version|2.9.6|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|Documentation for SinglePageModePlugin|
Normally, as you click on the links in TiddlyWiki, more and more tiddlers are displayed on the page. The order of this tiddler display depends upon when and where you have clicked. Some people like this non-linear method of reading the document, while others have reported that when many tiddlers have been opened, it can get somewhat confusing. SinglePageModePlugin allows you to configure TiddlyWiki to navigate more like a traditional multipage web site with only one item displayed at a time.
!!!!!Usage
<<<
When the plugin is enabled, only one tiddler will be displayed at a time and the browser window's titlebar is updated to include the current tiddler title. The browser's location URL is also updated with a 'permalink' for the current tiddler so that it is easier to create a browser 'bookmark' for the current tiddler. Alternatively, even when displaying multiple tiddlers //is// permitted, you can still reduce the potential for confusion by forcing tiddlers to always open at the top (or bottom) of the page instead of being displayed following the tiddler containing the link that was clicked.
<<<
!!!!!Configuration
<<<
<<option chkSinglePageMode>> Display one tiddler at a time
><<option chkSinglePagePermalink>> Automatically permalink current tiddler
><<option chkSinglePageKeepFoldedTiddlers>> Don't close tiddlers that are folded
><<option chkSinglePageKeepEditedTiddlers>> Don't close tiddlers that are being edited
<<option chkTopOfPageMode>> Open tiddlers at the top of the page
<<option chkBottomOfPageMode>> Open tiddlers at the bottom of the page
<<option chkSinglePageAutoScroll>> Automatically scroll tiddler into view (if needed)
Notes:
* {{block{
The "display one tiddler at a time" option can also be //temporarily// set/reset by including a 'paramifier' in the document URL: {{{#SPM:true}}} or {{{#SPM:false}}}. You can also use {{{SPM:expression}}}, where 'expression' is any javascript statement that evaluates to true or false. This allows you to create hard-coded links in other documents that can selectively enable/disable the use of this option based on various programmatic conditions, such as the current username. For example, using
{{{#SPM:config.options.txtUserName!="SomeName"}}}
enables 'one tiddler at a time' display for all users //other than// "~SomeName")}}}
* If more than one display mode is selected, 'one at a time' display takes precedence over both 'top' and 'bottom' settings, and if 'one at a time' setting is not used, 'top of page' takes precedence over 'bottom of page'.
* When using Apple's Safari browser, automatically setting the permalink causes an error and is disabled.
<<<
!!!!!Revisions
<<<
2008.10.17 2.9.6 changed chkSinglePageAutoScroll default to false
2008.06.12 2.9.5 corrected 'scroll to top of page' logic in auto-scroll handling
2008.06.11 2.9.4 added chkSinglePageKeepEditedTiddlers option
2008.06.05 2.9.3 in displayTiddler(), bypass single/top/bottom mode handling if startingUp. Allows multiple tiddlers to be displayed during startup processing (e.g., #story:DefaultTiddlers), even if single/top/bottom mode is enabled.
2008.04.18 2.9.2 in displayTiddler() and checkLastURL(), handling for Unicode in tiddler titles (remove explicit conversion between Unicode and UTF, as this is apparently done automatically by encode/decodeURIComponent, resulting in double-encoding!
2008.04.08 2.9.1 don't automatically add options to AdvancedOptions shadow tiddler
2008.04.02 2.9.0 in displayTiddler(), when single-page mode is in use and a tiddler is being edited, ask for permission to save-and-close that tiddler, instead of just leaving it open.
2008.03.29 2.8.3 in displayTiddler(), get title from tiddler object (if needed). Fixes errors caused when calling function passes a tiddler *object* instead of a tiddler *title*
2008.03.14 2.8.2 in displayTiddler(), if editing specified tiddler, just move it to top/bottom of story *without* re-rendering (prevents discard of partial edits).
2008.03.06 2.8.1 in paramifier handler, start 'checkURL' timer if chkSinglePageMode is enabled
2008.03.06 2.8.0 added option, {{{config.options.chkSinglePageKeepFoldedTiddlers}}}, so folded tiddlers won't be closed when using single-page mode. Also, in checkURL(), if hash is a ''permaview'' (e.g., "#foo bar baz"), then display multiple tiddlers rather than attempting to display "foo bar baz" as a single tiddler
2008.03.05 2.7.0 added support for "SPM:" URL paramifier
2008.03.01 2.6.0 in hijack of displayTiddler(), added 'title' argument to closeAllTiddlers() so that target tiddler isn't closed-and-reopened if it was already displayed. Also, added config.options.chkSinglePageAutoScrolloption to bypass automatic 'scroll into view' logic (note: core still does it's own ensureVisible() handling)
2007.12.22 2.5.3 in checkLastURL(), use decodeURIComponent() instead of decodeURI so that tiddler titles with commas (and/or other punctuation) are correctly handled.
2007.10.26 2.5.2 documentation cleanup
2007.10.08 2.5.1 in displayTiddler(), when using single-page or top-of-page mode, scrollTo(0,0) to ensure that page header is in view.
2007.09.13 2.5.0 for TPM/BPM modes, don't force tiddler to redisplay if already shown. Allows transition between view/edit or collapsed/view templates, without repositioning displayed tiddler.
2007.09.12 2.4.0 added option to disable automatic permalink feature. Also, Safari is now excluded from permalinking action to avoid bug where tiddlers don't display after hash is updated.
2007.03.03 2.3.1 fix typo when adding BPM option to AdvancedOptions (prevented checkbox from appearing)
2007.03.03 2.3.0 added support for BottomOfPageMode (BPM) based on request from DaveGarbutt
2007.02.06 2.2.3 in Story.prototype.displayTiddler(), use convertUnicodeToUTF8() for correct I18N string handling when creating URL hash string from tiddler title (based on bug report from BidiX)
2007.01.08 2.2.2 use apply() to invoke hijacked core functions
2006.07.04 2.2.1 in hijack for displayTiddlers(), suspend TPM as well as SPM so that DefaultTiddlers displays in the correct order.
2006.06.01 2.2.0 added chkTopOfPageMode (TPM) handling
2006.02.04 2.1.1 moved global variable declarations to config.* to avoid FireFox 1.5.0.1 crash bug when assigning to globals
2005.12.27 2.1.0 hijack displayTiddlers() so that SPM can be suspended during startup while displaying the DefaultTiddlers (or #hash list). Also, corrected initialization for undefined SPM flag to "false", so default behavior is to display multiple tiddlers
2005.12.27 2.0.0 Update for TW2.0
2005.11.24 1.1.2 When the back and forward buttons are used, the page now changes to match the URL. Based on code added by Clint Checketts
2005.10.14 1.1.1 permalink creation now calls encodeTiddlyLink() to handle tiddler titles with spaces in them
2005.10.14 1.1.0 added automatic setting of window title and location bar ('auto-permalink'). feature suggestion by David Dickens.
2005.10.09 1.0.1 combined documentation and code in a single tiddler
2005.08.15 1.0.0 Initial Release
<<<
Goljan. non-linear. 2010. 3rd ed. @@color:yellow;background-color:red;
This application is still in DEVELOPMENT. Check back for updates@@
/***
|Name|Snapshot+Plugin|
|Source|http://www.TiddlyTools.com/#SnapshotPlugin|
|Documentation|http://www.TiddlyTools.com/#SnapshotPluginInfo|
|Version|1.4.3|
|Author|Eric Shulman|
|@@modified@@|AXS,03/2011: modified/added (can't remember which) config.commands.snapshotPrintHere to automatically open a new snapshot window for that tiddler
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|save or print HTML+CSS image of rendered document content|
This plugin provides a macro as well as tiddler toolbar commands to create a file or browser window containing the //rendered// CSS-and-HTML that is currently being displayed for selected elements of the current document.
!!!!!Documentation
>see [[SnapshotPluginInfo]]
!!!!!Configuration
<<<
<<option chkSnapshotHTMLOnly>> output HTML only (omit CSS)
<<<
!!!!!Revisions
<<<
2011.02.14 1.4.3 fix OSX error: use picker.file.path
2011.01.03 1.4.2 added snapshotSaveViewer toolbar command
2010.12.15 1.4.1 added 'snapshot' class to wrapper
|please see [[SnapshotPluginInfo]] for additional revision details|
2008.04.21 1.0.0 initial release - derived from [[NewDocumentPlugin]] with many improvements...
<<<
!!!!!Code
***/
//{{{
version.extensions.SnapshotPlugin= {major: 1, minor: 4, revision: 3, date: new Date(2011,2,14)};
if (config.options.chkSnapshotHTMLOnly===undefined)
config.options.chkSnapshotHTMLOnly=false;
config.macros.snapshot = {
snapLabel: "save a snapshot",
printLabel: "print a snapshot",
snapPrompt: "save an HTML image",
printPrompt: "print an HTML image",
hereID: "here",
viewerID: "viewer",
storyID: "story",
allID: "all",
askID: "ask",
askTiddlerID: "askTiddler",
askDOMID: "askDOM",
askMsg: "select an element...",
hereItem: "tiddler: '%0'",
viewerItem: "tiddler: '%0' (content only)",
storyItem: "story column (one file)",
storyFilesItem: "story column (multiple files)",
allItem: "entire document",
tiddlerItem: "select a tiddler...",
IDItem: "select a DOM element by ID...",
HTMLItem: "[%0] output HTML only (omit CSS)",
fileMsg: "select or enter a target path/filename",
defaultFilename: "snapshot.html",
okmsg: "snapshot written to %0",
failmsg: "An error occurred while creating %0",
handler: function(place,macroName,params,wikifier,paramString,tiddler) {
var printing=params[0]&¶ms[0]=="print"; if (printing) params.shift();
params = paramString.parseParams("anon",null,true,false,false);
var id=getParam(params,"id","here");
var label=getParam(params,"label",printing?this.printLabel:this.snapLabel);
var prompt=getParam(params,"prompt",printing?this.printPrompt:this.snapPrompt);
var btn=createTiddlyButton(place,label,prompt, function(ev){
this.setAttribute("snapID",this.getAttribute("startID"));
config.macros.snapshot.go(this,ev)
});
btn.setAttribute("startID",id);
btn.setAttribute("snapID",id);
btn.setAttribute("printing",printing?"true":"false");
btn.setAttribute("HTMLOnly",config.options.chkSnapshotHTMLOnly?"true":"false");
},
go: function(here,ev) {
var cms=config.macros.snapshot; // abbreviation
var id=here.getAttribute("snapID");
var printing=here.getAttribute("printing")=="true";
var HTMLOnly=here.getAttribute("HTMLOnly")=="true";
if (id==cms.askID||id==cms.askTiddlerID||id==cms.askDOMID) {
cms.askForID(here,ev);
} else if (id==cms.storyID) {
story.forEachTiddler(function(t,e) {
var out=cms.getsnap(e,e.id,printing,HTMLOnly);
if (printing) cms.printsnap(out);
else cms.savesnap(out,e.getAttribute('tiddler')+'.html');
});
} else {
if (id==cms.allID) id="contentWrapper";
var snapElem=document.getElementById(id);
if (id==cms.hereID || id==cms.viewerID)
var snapElem=story.findContainingTiddler(here);
if (snapElem && hasClass(snapElem,"tiddler") && (id==cms.viewerID || HTMLOnly)) {
// find viewer class element within tiddler element
var nodes=snapElem.getElementsByTagName("*");
for (var i=0; i<nodes.length; i++)
if (hasClass(nodes[i],"viewer")) { snapElem=nodes[i]; break; }
}
if (!snapElem) // not in a tiddler or no viewer element or unknown ID
{ e.cancelBubble=true; if(e.stopPropagation)e.stopPropagation(); return(false); }
// write or print snapshot
var out=cms.getsnap(snapElem,id,printing,HTMLOnly);
if (printing) cms.printsnap(out); else cms.savesnap(out);
}
return false;
},
askForID: function(here,ev) {
var ev = ev ? ev : window.event;
var cms=config.macros.snapshot; // abbreviation
var id=here.getAttribute("snapID");
var indent='\xa0\xa0\xa0\xa0';
var p=Popup.create(here); if (!p) return false; p.className+=' sticky smallform';
var s=createTiddlyElement(p,'select'); s.button=here;
if (id==cms.askID) {
s.options[s.length]=new Option(cms.askMsg,cms.askID);
var tid=story.findContainingTiddler(here);
if(tid) {
var title=tid.getAttribute("tiddler");
if (here.getAttribute("HTMLOnly")!="true")
s.options[s.length]=new Option(indent+cms.hereItem.format([title]),cms.hereID);
s.options[s.length]=new Option(indent+cms.viewerItem.format([title]),cms.viewerID);
}
s.options[s.length]=new Option(indent+cms.tiddlerItem,cms.askTiddlerID);
s.options[s.length]=new Option(indent+cms.IDItem,cms.askDOMID);
s.options[s.length]=new Option(indent+cms.storyItem,"tiddlerDisplay");
s.options[s.length]=new Option(indent+cms.storyFilesItem,cms.storyID);
s.options[s.length]=new Option(indent+cms.allItem,"contentWrapper");
}
if (id==cms.askDOMID) {
s.options[s.length]=new Option(cms.IDItem,cms.askDOMID);
var elems=document.getElementsByTagName("*");
var ids=[];
for (var i=0;i<elems.length;i++)
if (elems[i].id.length && elems[i].className!="animationContainer")
ids.push(elems[i].id);
ids.sort();
for (var i=0;i<ids.length;i++) s.options[s.length]=new Option(indent+ids[i],ids[i]);
}
if (id==cms.askTiddlerID) {
s.options[s.length]=new Option(cms.tiddlerItem,cms.askTiddlerID);
var elems=document.getElementsByTagName("div");
var ids=[];
for (var i=0;i<elems.length;i++) { var id=elems[i].id;
if (id.length && id.substr(0,story.idPrefix.length)==story.idPrefix && id!="tiddlerDisplay")
ids.push(id);
}
ids.sort();
for (var i=0;i<ids.length;i++) s.options[s.length]=new Option(indent+ids[i].substr(story.idPrefix.length),ids[i]);
}
s.options[s.length]=new Option(cms.HTMLItem.format([here.getAttribute("HTMLOnly")=="true"?"\u221a":"_"]),cms.HTMLItem);
s.onchange=function(ev){
var ev = ev ? ev : window.event;
var cms=config.macros.snapshot; // abbreviation
var here=this.button;
if (this.value==cms.HTMLItem) {
config.options.chkSnapshotHTMLOnly=!config.options.chkSnapshotHTMLOnly;
here.setAttribute("HTMLOnly",config.options.chkSnapshotHTMLOnly?"true":"false");
config.macros.option.propagateOption("chkSnapshotHTMLOnly","checked",
config.options.chkSnapshotHTMLOnly,"input");
} else
here.setAttribute("snapID",this.value);
config.macros.snapshot.go(here,ev);
return false;
};
Popup.show();
ev.cancelBubble=true;
if(ev.stopPropagation)ev.stopPropagation();
return false;
},
getpath: function() {
// get current path
var path=getLocalPath(window.location.href);
var slashpos=path.lastIndexOf("/");
if (slashpos==-1) slashpos=path.lastIndexOf("\\");
if (slashpos!=-1) path=path.substr(0,slashpos+1); // trim filename
return path;
},
getsnap: function(snapElem,id,printing,HTMLOnly) {
var cms=config.macros.snapshot; // abbreviation
var out='<head><meta http-equiv="Content-Type" content="text/html;charset=utf-8" />';
if (printing)
out+='<base href="file:///'+cms.getpath().replace(/\\/g,'/')+'"></base>\n';
if (!HTMLOnly) {
var styles=document.getElementsByTagName('style');
var fmt='<style>\n/* stylesheet=%0 */\n%1\n\n</style>\n';
for(var i=0; i < styles.length; i++)
out+=fmt.format([styles[i].getAttribute('id'),styles[i].innerHTML]);
}
out+='</head>\n';
var elems=snapElem.getElementsByTagName('input');
for (var i=0; i<elems.length; i++) { var e=elems[i];
if (e.type=='text') e.defaultValue=e.value;
if (e.type=='checkbox') e.defaultChecked=e.checked;
if (e.type=='radiobutton') e.defaultChecked=e.checked;
}
var elems=snapElem.getElementsByTagName('textarea');
for (var i=0; i<elems.length; i++) elems[i].defaultValue=elems[i].value;
var fmt='<body>\n\n<div class="snapshot %0">%1</div>\n\n</body>\n';
out+=fmt.format([(id==cms.viewerID?'tiddler viewer':''),snapElem.innerHTML]);
return '<html>\n'+out+'</html>';
},
printsnap: function(out) {
var win=window.open("","_blank","");
win.document.open();
win.document.writeln(out);
win.document.close();
win.focus(); // bring to front
//win.print(); // trigger print dialog //edited by AS Feb27,2011
},
savesnap: function(out,target) {
var cms=config.macros.snapshot; // abbreviation
// make sure we are local
if (window.location.protocol!="file:")
{ alert(config.messages.notFileUrlError); return; }
var target=target||cms.askForFilename(cms.fileMsg,cms.getpath(),cms.defaultFilename);
if (!target) return; // cancelled by user
// if specified file does not include a path, assemble fully qualified path and filename
var slashpos=target.lastIndexOf("/"); if (slashpos==-1) slashpos=target.lastIndexOf("\\");
if (slashpos==-1) {
var h=document.location.href;
var cwd=getLocalPath(decodeURIComponent(h.substr(0,h.lastIndexOf('/')+1)));
target=cwd+target;
}
var link="file:///"+target.replace(/\\/g,'/'); // link for message text
var ok=saveFile(target,convertUnicodeToUTF8(out));
var msg=ok?cms.okmsg.format([target]):cms.failmsg.format([target]);
displayMessage(msg,link);
},
askForFilename: function(msg,path,file) {
if(window.Components) { // moz
try {
netscape.security.PrivilegeManager.enablePrivilege('UniversalXPConnect');
var nsIFilePicker = window.Components.interfaces.nsIFilePicker;
var picker = Components.classes['@mozilla.org/filepicker;1'].createInstance(nsIFilePicker);
picker.init(window, msg, nsIFilePicker.modeSave);
var thispath = Components.classes['@mozilla.org/file/local;1'].createInstance(Components.interfaces.nsILocalFile);
thispath.initWithPath(path);
picker.displayDirectory=thispath;
picker.defaultExtension='html';
picker.defaultString=file;
picker.appendFilters(nsIFilePicker.filterAll|nsIFilePicker.filterText|nsIFilePicker.filterHTML);
if (picker.show()!=nsIFilePicker.returnCancel) var result=picker.file.path;
}
catch(e) { alert('error during local file access: '+e.toString()) }
}
else { // IE
try { // XP/Vista only
var s = new ActiveXObject('UserAccounts.CommonDialog');
s.Filter='All files|*.*|Text files|*.txt|HTML files|*.htm;*.html|';
s.FilterIndex=3; // default to HTML files;
s.InitialDir=path;
s.FileName=file;
if (s.showOpen()) var result=s.FileName;
}
catch(e) { var result=prompt(msg,path+file); } // fallback for non-XP IE
}
return result;
}
};
//}}}
// // TOOLBAR DEFINITIONS
//{{{
config.commands.snapshotSave = {
text: "snap",
tooltip: config.macros.snapshot.snapPrompt,
handler: function(ev,src,title) {
src.setAttribute("snapID","ask");
src.setAttribute("printing","false");
src.setAttribute("HTMLOnly",config.options.chkSnapshotHTMLOnly?"true":"false");
config.macros.snapshot.go(src,ev);
return false;
}
};
config.commands.snapshotSaveViewer = {
text: "snap",
tooltip: config.macros.snapshot.snapPrompt,
handler: function(ev,src,title) {
src.setAttribute("snapID","viewer");
src.setAttribute("printing","false");
src.setAttribute("HTMLOnly",config.options.chkSnapshotHTMLOnly?"true":"false");
config.macros.snapshot.go(src,ev);
return false;
}
};
config.commands.snapshotPrint = {
text: "print",
tooltip: config.macros.snapshot.printPrompt,
handler: function(ev,src,title) {
src.setAttribute("snapID","ask");
src.setAttribute("printing","true");
src.setAttribute("HTMLOnly",config.options.chkSnapshotHTMLOnly?"true":"false");
config.macros.snapshot.go(src,ev);
return false;
}
};
config.commands.snapshotPrintHere = {
text: "print",
tooltip: config.macros.snapshot.printPrompt,
handler: function(ev,src,title) {
src.setAttribute("snapID","here");
src.setAttribute("printing","true");
src.setAttribute("HTMLOnly",config.options.chkSnapshotHTMLOnly?"true":"false");
config.macros.snapshot.go(src,ev);
return false;
}
};
config.commands.snapshotPrintViewer = {
text: "print",
tooltip: config.macros.snapshot.printPrompt,
handler: function(ev,src,title) {
src.setAttribute("snapID","viewer");
src.setAttribute("printing","true");
src.setAttribute("HTMLOnly",config.options.chkSnapshotHTMLOnly?"true":"false");
config.macros.snapshot.go(src,ev);
return false;
}
};
//}}}
// // COPIED FROM [[StickyPopupPlugin]] TO ELIMINATE PLUGIN DEPENDENCY
//{{{
if (config.options.chkStickyPopups==undefined) config.options.chkStickyPopups=false;
Popup.stickyPopup_onDocumentClick = function(ev)
{
// if click is in a sticky popup, ignore it so popup will remain visible
var e = ev ? ev : window.event; var target = resolveTarget(e);
var p=target; while (p) {
if (hasClass(p,"popup") && (hasClass(p,"sticky")||config.options.chkStickyPopups)) break;
else p=p.parentNode;
}
if (!p) // not in sticky popup (or sticky popups disabled)... use normal click handling
Popup.onDocumentClick(ev);
return true;
};
try{removeEvent(document,"click",Popup.onDocumentClick);}catch(e){};
try{addEvent(document,"click",Popup.stickyPopup_onDocumentClick);}catch(e){};
//}}}
/***
|Name|SnapshotPluginInfo|
|Source|http://www.TiddlyTools.com/#SnapshotPlugin|
|Documentation|http://www.TiddlyTools.com/#SnapshotPluginInfo|
|Version|1.4.2|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|Documentation for SnapshotPlugin|
This plugin provides a macro as well as tiddler toolbar commands that creates a file or opens a new browser window containing the //rendered// HTML and CSS style definitions that are being displayed for selected elements of the current document.
!!!!!Usage:
<<<
As a macro embedded in tiddler content:
{{{
<<snapshot print label:text prompt:text id:elementID|here|viewer|story|all|ask>
}}}
where:
*''print'' //(optional)//<br>when present, causes the snapshot output to be directed to a new browser tab/window instead of saving it to a file. In addition, the print dialog for that tab/window is automatically invoked.
*''label'' //(optional)//<br>is the text to be displayed for the command link generated by the macro
*''prompt'' //(optional)//<br>is the 'tool tip' message displayed when you mouseover the command link
*''id:...'' //(optional)//<br>specifies the document element to be captured, and can be one of:
**''elementID''<br>is a specific DOM element ID, such as "displayArea", "mainMenu", "contentWrapper", etc.
**''here''<br>the containing tiddler in which the macro (or toolbar command) occurs, including the tiddler title and subtitle (date/time/author) information.
**''viewer''<br>same as ''here'', but omits the tiddler title, subtitle and toolbar elements (i.e., it includes //only// the content of the tiddler)
**''story''<br>selects all currently displayed tiddlers (i.e., the 'story column')
**''all''<br>selects the entire document contents, including page header, main menu and sidebar displays
**''ask''<br>when the snapshot command link is clicked, a droplist is displayed so you can choose from several pre-defined elements: "current tiddler", "story column", or "entire document", or "DOM element ID..." When DOM element ID is chosen, the droplist is refreshed to show the individual ID's for all currently rendered DOM elements (at least, the ones that have ID's). For any given DOM element ID, only the portions of the document that are contained //within// the specified DOM element will be transcribed to the resulting snapshot or print output.
//''NOTE: when no parameters are specified, the macro creates a snapshot file using the containing tiddler as the default element.'' (e.g., equivalent to {{{<<snapshot id:here>>}}}//
The snapshot/print functions can also be embedded as tiddler toolbar commands in [[ViewTemplate]]:
{{{
<span class='toolbar' macro='toolbar snapshotSave'></span>
<span class='toolbar' macro='toolbar snapshotSaveViewer'></span>
<span class='toolbar' macro='toolbar snapshotPrint'></span>
<span class='toolbar' macro='toolbar snapshotPrintViewer'></span>
}}}
* By default, the toolbar commands use the "id:ask" option to display a droplist of elements to select from. The "...Viewer" form of each command bypasses the droplist and automatically selects the current tiddler viewer area for saving/printing.
Please note that, although the snapshot/print that is created using the HTML+CSS of the displayed content, ''there is NO javascript code'' written into the snapshot. As a result, the snapshot only ''reproduces the //appearance// of the displayed content, allowing you to //view// or //print// the result'', but does not permit you to interact with it in other ways.
For example, even simple processing (such as mouseover highlighting) will not function from the snapshot. You can't click a TiddlyLink to open other tiddlers, because A) there is no code that handles the click and B) there is no underlying 'storeArea' (and core code) to retrieve and render anything! You also can't use ANY command links, since these also require javascript code (and the core) to operate.
__''Custom CSS for printing''__
There can be differences in the appearance of snapshot output when rendered on different devices (e.g. screen vs. printer). Although these differences are typically very minor, it is sometimes necessary to define alternative CSS styles to account for the differences in device characteristics, such as font metrics, page sizes, resolutions, etc. You can use the {{{@@media}}} wrapper within your custom StyleSheet CSS to define printer-specific formatting:
{{{
@media print {
...
}
}}}
The plugin places the snapshot output within a custom CSS class wrapper, using the classname, "{{{.snapshot}}}". This enables you to define and apply custom formatting rules to 'fine tune' the appearance of the snapshot output, regardless of the intended output device. For example, the following rule will override and hide tiddler borders and background colors when displaying and/or printing snapshots.
{{{
.snapshot .viewer { border:0 !important; background-color:none !important; }
}}}
<<<
!!!!!Examples:
<<<
{{{<<snapshot>>}}}: <<snapshot>>
{{{<<snapshot id:mainMenu>>}}}: <<snapshot id:mainMenu>>
{{{<<snapshot print id:story>>}}}: <<snapshot print id:story>>
{{{<<snapshot print id:ask>>}}}: <<snapshot print id:ask>>
{{{<<snapshot print noCSS id:viewer>>}}}: <<snapshot print noCSS id:viewer>>
<<<
!!!!!Configuration
<<<
<<option chkSnapshotHTMLOnly>> output HTML only (omit CSS)
<<<
!!!!!Revisions
<<<
2011.01.03 1.4.2 added snapshotSaveViewer toolbar command
2010.12.15 1.4.1 added 'snapshot' class to wrapper
2010.11.20 1.4.0 added snapshotPrintViewer toolbar command
2009.10.12 1.3.0 added multi-file story snapshot
2009.09.25 1.2.1 in getSnap(), added META tag to set UTF-8 encoding for I18N support
2009.06.04 1.2.0 added handling in getSnap() so current form input values are shown in snapshots
2008.05.16 1.1.1 added try..catch around addEvent/removeEvent calls to avoid error in Opera
2008.04.28 1.1.0 removed 'viewerHTML' from 'ask' droplist and replaced with toggle for "output HTML only". Removed 'noCSS' parameter and replaced with config.options.chkSnapshotHTMLOnly global option. Added "select a tiddler..." to 'ask' droplist
2008.04.24 1.0.1 in saveSnap(), convert output from Unicode to UTF before passing to saveFile(). Fixes "unknown name" error in IE's file.Write() function.
2008.04.21 1.0.0 initial release - derived from [[NewDocumentPlugin]] with many improvements, including: "ask for ID" using droplist of available DOM elements, use "<base href=...>" for correctly resolving image references, wrap 'viewer only' output in class="tiddler viewer" for proper application of inherited CSS styles, snapshotSave and snapshotPrint tiddler toolbar command definitions, and more...
__Excerpted revisions from [[NewDocumentPlugin]] (obsolete)__
2008.04.20 1.8.0 added support for 'noCSS' and 'viewer' params for alternative snapshot output
2007.03.30 1.7.0 added support for "print" param as alternative for "snap". When "print" is used, the filename is ignored and ouput is directed to another browser tab/window, where the print dialog is then automatically triggered.
2007.03.30 1.6.1 added support for "here" keyword for current tiddler elementID and "prompt:text" param for specifying tooltip text
2006.10.18 1.5.0 new optional param for 'snap'... specify alternative DOM element ID (default is still "contentWrapper"). Based on a suggestion from Xavier Verges.
2006.03.09 1.2.0 added special "snap" filter parameter to generate and write "snapshot" files containing static HTML+CSS for currently rendered document.
2006.02.03 1.0.0 Created.
<<<
/***
''Inspired by [[TiddlyPom|http://www.warwick.ac.uk/~tuspam/tiddlypom.html]]''
|Name|SplashScreenPlugin|
|Created by|SaqImtiaz|
|Location|http://tw.lewcid.org/#SplashScreenPlugin|
|Version|0.21 |
|Requires|~TW2.08+|
!Description:
Provides a simple splash screen that is visible while the TW is loading.
!Installation
Copy the source text of this tiddler to your TW in a new tiddler, tag it with systemConfig and save and reload. The SplashScreen will now be installed and will be visible the next time you reload your TW.
!Customizing
Once the SplashScreen has been installed and you have reloaded your TW, the splash screen html will be present in the MarkupPreHead tiddler. You can edit it and customize to your needs.
!History
* 20-07-06 : version 0.21, modified to hide contentWrapper while SplashScreen is displayed.
* 26-06-06 : version 0.2, first release
!Code
***/
//{{{
window.old_lewcid_splash_restart=window.restart;
window.restart = function()
{ if (document.getElementById("SplashScreen"))
document.getElementById("SplashScreen").style.display = "none";
if (document.getElementById("contentWrapper"))
document.getElementById("contentWrapper").style.display = "block";
window.old_lewcid_splash_restart();
if (splashScreenInstall)
{if(config.options.chkAutoSave)
{saveChanges();}
displayMessage("TW SplashScreen has been installed, please save and refresh your TW.");
}
}
var oldText = store.getTiddlerText("MarkupPreHead");
if (oldText.indexOf("SplashScreen")==-1)
{var siteTitle = store.getTiddlerText("SiteTitle");
var splasher='\n\n<style type="text/css">#contentWrapper {display:none;}</style><div id="SplashScreen" style="border: 3px solid #ccc; display: block; text-align: center; width: 320px; margin: 100px auto; padding: 50px; color:#000; font-size: 28px; font-family:Tahoma; background-color:#eee;"><b>'+siteTitle +'</b> is loading<blink> ...</blink><br><br><span style="font-size: 14px; color:red;">Requires Javascript.</span></div>';
if (! store.tiddlerExists("MarkupPreHead"))
{var myTiddler = store.createTiddler("MarkupPreHead");}
else
{var myTiddler = store.getTiddler("MarkupPreHead");}
myTiddler.set(myTiddler.title,oldText+splasher,config.options.txtUserName,null,null);
store.setDirty(true);
var splashScreenInstall = true;
}
//}}}
/***
|Name|StickyPopupPlugin|
|Source|http://www.TiddlyTools.com/#StickyPopupPlugin|
|Version|1.0.1|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|allow mouse interactions inside popups without automatically closing them|
Usually, when a TW popup is displayed, it is automatically closed whenever a click occurs //anywhere// in the document, either //inside// or //outside// the popup itself. This plugin makes popups persistent (a.k.a, "sticky"), allowing you to perform multiple mouse interactions on content //inside// the popup (e.g., entering form fields, opening links, selecting text, etc.), remaining visible until you click //outside// the popup or perform an action that opens another popup (only one popup can be displayed at any given time).
!!!!!Configuration
<<<
You can cause popups to behave in a persistent ("sticky") manner simply by selecting the option checkbox below. The selected popup display behavior will be applied to ALL popups in the document automatically.
><<option chkStickyPopups>> make all popups "sticky"
>{{{usage: <<option chkStickyPopups>>}}}
<<<
!!!!!Usage
<<<
If you are developing your own plugins or inline scripts that create popups programmatically using the core function:
{{{
Popup.create(this)
}}}
you can provide additional parameters that specify the desired CSS classname(s) to assign to the popup DOM element. The default class when none is specified is simply "popup". To create a //sticky// popup, simply enter a custom class combination like this:
{{{
Popup.create(this,null,"sticky popup")
}}}
<<<
!!!!!Revisions
<<<
2008.05.16 [1.0.1] added try..catch around addEvent/removeEvent calls to avoid error in Opera
2007.11.25 [1.0.0] initial release - moved from [[CoreTweaks]]
<<<
!!!!!Code
***/
//{{{
version.extensions.StickyPopupPlugin= {major: 1, minor: 0, revision: 1, date: new Date(2008,5,16)};
if (config.options.chkStickyPopups==undefined) config.options.chkStickyPopups=false;
Popup.stickyPopup_onDocumentClick = function(ev)
{
// if click is in a sticky popup, ignore it so popup will remain visible
var e = ev ? ev : window.event; var target = resolveTarget(e);
var p=target; while (p) {
if (hasClass(p,"popup") && (hasClass(p,"sticky")||config.options.chkStickyPopups)) break;
else p=p.parentNode;
}
if (!p) // not in sticky popup (or sticky popups disabled)... use normal click handling
Popup.onDocumentClick(ev);
return true;
};
try{removeEvent(document,"click",Popup.onDocumentClick);}catch(e){};
try{addEvent(document,"click",Popup.stickyPopup_onDocumentClick);}catch(e){};
//}}}
/***
|Name|StorySaverPlugin|
|Source|http://www.TiddlyTools.com/#StorySaverPlugin|
|Documentation|http://www.TiddlyTools.com/#StorySaverPluginInfo|
|Version|1.8.3|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Requires|MarkupPostBody|
|Description|documentation for [[StorySaverPlugin]]|
Automatically saves a list of currently viewed tiddlers (the "story") in a local cookie, {{{txtSavedStory}}} and then opens those tiddlers when the document is subsequently reloaded, allowing you to quickly resume working with the document from the same place you left off!! The plugin also defines {{{<<saveStory>>}}} and {{{<<openStory>>}}} macros that allow you to quickly save/re-display stories stored in tiddlers, using simple, one-click command links or droplists.
!!!!!Usage
<<<
If a document URL does not contain a paramifier (i.e., a "#..." suffix), then the saved story cookie (if any) will be used //as if// it had been entered as a permaview (e.g., a "#tiddler tiddler tiddler..." suffix on the URL), bypassing the [[DefaultTiddlers]] definition. This behavior is automatically applied whenever the plugin is installed in your document. You can enable/disable the automatic cookie-based StorySaver feature by using the checkbox below:
><<option chkSaveStory>> enable StorySaverPlugin
>//usage:// {{{<<option chkSaveStory>>}}}
You can also temporarily //bypass// the redisplay of a saved story ''without disabling the StorySaver cookie'' by including a trailing "#" at the end of the document URL. This will cause your document to be loaded into the browser without displaying //any// initial tiddlers at all. Alternatively, you can enter {{{#story:storyname}}} on the end of the URL (e.g., {{{#story:DefaultTiddlers}}}) to display any specific saved story, regardless of the value of the cookie-based saved story.
__''saveStory macro:''__
The {{{<<saveStory>>}}} macro lets you write the list of currently viewed tiddlers to a specified tiddler name (e.g., DefaultTiddlers, MyFavorites, etc.). Tiddlers containing saved stories are automatically tagged with <<tag story>>, so that they can be recognized by the {{{<<storyViewer>>}}} macro (see [[StoryViewerPlugin]]). The syntax for the {{{<<saveStory>>}}} macro is:
{{{
<<saveStory storyname label tooltip tag tag tag...>>
}}}
*''storyname''<br>is the target tiddler in which to save the current story. If you use the keyword, ''ask'', in place of the tiddlername, you will be prompted to enter a tiddler title when saving the story (default: DefaultTiddlers).
*''label'' and ''tooltip''<br>are the link text and mouseover guide-text
*''tag tag tag...'' (optional)<br>are extra tags that are added when saving a story tiddler (in addition to the default<<tag story>>tag).
__''openStory macro:''__
To redisplay a saved story, the {{{<<openStory>>}}} macro can be used to embed either a droplist of all saved stories, or a link for a specified story. Selecting from the droplist or clicking the link opens the corresponding set of tiddlers.
{{{
<<openStory list tagValue>>
<<openStory popup label tooltip tagValue>>
<<openStory storyname label tooltip fold>>
}}}
*''list''<br>shows a droplist of all saved stories, plus additional commands/viewing options. Selecting a story opens the corresponding tiddlers.
*''popup''<br>shows a popup display containing a list of all saved stories, plus additional commands/viewing options. Selecting a story opens the corresponding tiddlers. ''label'' and ''tooltip'' are optional and provide alternative display text and mouseover help text, respectively.
*''storyname''<br>is a tiddler containing a saved story. //Note: You can also use a tag value as a storyname, in which case the story view will be composed of all tiddlers tagged with the specified tag value.//
*''label''<br>is the command link text (default: "open story: %0", where %0 is replaced by the storyname).
*''tooltip''<br>is the command mouseover guide-text (default: "open the set of tiddlers listed in: '%0'"),
*''tagValue'' (optional, default='story')<br>specifies an alternative tag value to match when listing story tiddlers. Note: if MatchTagsPlugin is installed, you can also use a compound //boolean tag expression//, enclosed within doubled square brackets.
*''fold''<br>If this optional keyword is present, the story tiddlers are initially 'folded' using [[CollapsedTemplate]] instead of the usual [[ViewTemplate]] (see [[CollapseTiddlersPlugin]]).
__''excludeStory tag:''__
Any tiddlers tagged with<<tag excludeStory>>will be automatically omitted when creating new story tiddlers with {{{<<saveStory>>}}}. Similarly, if a tiddler that is part of a saved story is tagged with<<tag excludeStory>>, it will not be displayed when that story is opened via {{{<<openStory>>}}}.
__''PermaView command link enhancement:''__
In order to further aide in saving/restoring the list of tiddlers currently being viewed, the core {{{<<permaview>>}}} command has been enhanced, so its link value always includes the current story view tiddler list as a paramifier in the URL. This let you quickly use the browser's right-click menu directly on the permalink command text to "bookmark this link...". Depending upon your system, you may also be able to drag the 'permaview' link directly from the page and drop it onto your desktop to create an instant permaview-bearing URL shortcut icon.
<<<
!!!!!Examples
<<<
*{{{<<saveStory TestStory "save a test story">>}}}<br>{{smallform{<<saveStory TestStory "save a test story">>}}}
*{{{<<openStory TestStory>>}}}<br><<openStory TestStory>>
*{{{<<openStory list>>}}}<br>{{smallform{<<openStory list>>}}}
*{{{<<openStory popup label tooltip>>}}}<br>{{smallform{<<openStory popup>>}}}
<<<
!!!!!Configuration
<<<
<<option chkSaveStory>> use automatic story cookie (reopens tiddlers on startup)
<<option chkStoryAllowAdd>>include 'add a story' command in droplist/popup
<<option chkStoryFold>>fold story tiddlers when opening a story (see [[CollapseTiddlersPlugin]])
<<option chkStoryClose>>close other tiddlers when opening a story
<<option chkStoryTop>>open story tiddlers at top of column
<<option chkStoryBottom>>open story tiddlers at bottom of column
<<<
!!!!!Revisions
<<<
2009.10.20 1.8.3 fix handling for 'add' item in popup menu
2009.08.29 1.8.2 added 'return false' to all button handlers to fix IE page-transition error
2009.08.23 1.8.1 fixed 'excludeStory' handling for links to missing tiddlers
2009.08.20 1.8.0 added 'excludeStory' tag handling
2009.07.27 1.7.1 corrected test for {{{chkStoryAllowAdd}}} when rendering //list// output
2009.07.27 1.7.0 added options: {{{chkStoryAllowAdd=true}}}, {{{chkStoryTop=true}}}, and {{{chkStoryBottom=false}}}. Also, autoscroll to first tiddler in story
2009.07.26 1.6.0 added optional 'extratags' param to {{{<<saveStory>>}}} and 'tagfilter' to {{{<<openStory>>}}}
2009.07.06 1.5.1 in setTiddler(), use pushUnique() to avoid double 'story' tag
2009.04.24 1.5.0 added optional 'fold' param to {{{<<openStory StoryName ...>>}}} macro
2008.09.07 1.4.3 added removeCookie() function for compatibility with [[CookieManagerPlugin]]
2008.07.11 1.4.2 in confirmExit(), corrected bracketing for titles containing spaces
2008.03.10 [*.*.*] plugin size reduction: documentation moved to [[StorySaverPluginInfo]]
2008.01.01 1.4.1 sort list of stories alphabetically
2008.01.01 1.4.0 added popup option
2007.12.31 1.3.1 instead of readBracketedList(), use internal tiddler.links[] to retrieve story list from tiddler content. Allows more flexible formatting of story tiddler content: anything content that is not a tiddler link is automatically filtered out of the list.
2007.10.23 1.3.0 split {{{<<storyViewer>>}}} macro definition into stand-alone [[StoryViewerPlugin]] to allow separate installation of story saving vs. story viewing features.
2007.10.21 1.2.0 added {{{<<openStory>>}}} and {{{<<storyViewer>>}}} macros.
2007.10.20 1.1.0 in setTiddler(), automatically add "story" tag to saved story tiddlers
2007.10.18 1.0.1 added default initialization for chkSaveStory option value. Also, in setTiddler(), call displayTiddler() after saving story to ensure that altered tiddler is shown to the user.
2007.10.05 1.0.0 initial release. Moved [[SetDefaultTiddlers]] inline script and rewrote as a {{{<<saveStory>>}}} macro. Moved permaview "mouseover HREF" enhancement from [[CoreTweaks]].
<<<
/***
|Name|StoryViewerPluginInfo|
|Source|http://www.TiddlyTools.com/#StoryViewerPlugin|
|Documentation|http://www.TiddlyTools.com/#StoryViewerPluginInfo|
|Version|1.3.4|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|documentation for StoryViewerPlugin|
The {{{<<storyViewer>>}}} macro allows you to quickly ''display //and// navigate between a set of tiddlers'', using a droplist of titles and/or individual "first/previous/next/last" buttons/text links. It also provides a "slideshow" feature that permits you to ''present one tiddler at a time with a countdown timer to automatically advance to the next tiddler'' after a specified number of seconds.
!!!!!Usage
<<<
{{{
<<storyViewer storyname|tagvalue list buttonoption prompt:...>>
<<storyViewer storyname|tagvalue first|previous|here|next|last>>
<<storyViewer storyname|tagvalue links>>
<<storyViewer storyname|tagvalue timer:nnn autostart close|fold>>
}}}
where:
* ''storyname'' or ''tagvalue''<br>specifies a "saved story": a set of tiddler titles, defined by matching a specified tag, or by creating a tiddler tagged with <<tag story>>, containing a space-separated list of titles. ''You can use the {{{<<saveStory>>}}} macro (see [[StorySaverPlugin]]) to automatically create stories using the titles of the tiddlers that are currently being viewed.'' If you omit the storyname/tagname parameter, the plugin will attempt to identify a suitable story by locating the current tiddler title within a saved story tiddler. The story view controls are not displayed unless the current tiddler title is explicitly found in at least one saved story.
** Note: if [[MatchTagsPlugin]] is installed, you can use a compound //boolean tag expression//, enclosed within doubled square brackets. This allows you to generate sets of stories based on complex combinations of tags, rather than matching just one tag value.
* ''list''<br>displays a droplist of tiddlers for the specified story, along with previous/next pushbuttons on either side of the list. You can also specify an //optional// parameter to indicate which buttons will appear when using the droplist display:
** ''allbuttons''<br>displays buttons for first/last as well as previous/next.
** ''nobuttons''<br>displays the droplist without any buttons
** ''onlybuttons''<br>hides the droplist and shows just the buttons
* ''first'' or ''previous'' or ''here'' or ''next'' or ''last''<br>displays an individual link to the indicated tiddler within the story. The next/previous links are automatically calculated relative to the current tiddler. ''here'' displays the current tiddler title.
* ''links''<br>displays the set of first, previous, here, next and last links with just one convenient macro invocation, allowing you to quickly and easily embed story navigation links into any tiddler content.
* ''timer:nnn''<br>displays an automatic countdown 'slideshow' timer, where ''nnn'' is the number of seconds between slides. Click on the timer to start the countdown. The countdown is paused when hovering over the timer. Click a //running// timer to immediately advance to the next tiddler in the story. Optional slideshow parameters:
** ''autostart''<br>automatically starts the countdown without an initial click.
** ''close'' or ''fold''<br>close or fold (see [[CollapseTiddlerPlugin]]) the current tiddler when the next tiddler in the story is opened. The default is to simply display the next tiddler following the current one.
<<<
!!!!!Examples
<<<
{{smallform{
{{{
<<storyViewer MenuDefinitions list nobuttons>>
}}}
><<storyViewer MenuDefinitions list nobuttons>> //uses "saved story" tiddler//
{{{
<<storyViewer pluginInfo>>
}}}
><<storyViewer pluginInfo>>
{{{
<<storyViewer pluginInfo list allbuttons prompt:"TiddlyTools menu definitions...">>
}}}
><<storyViewer pluginInfo list allbuttons prompt:"TiddlyTools menu definitions...">>
{{{
<<storyViewer pluginInfo first>>
<<storyViewer pluginInfo previous>>
<<storyViewer pluginInfo next>>
<<storyViewer pluginInfo last>>
}}}
><<storyViewer pluginInfo first>>
><<storyViewer pluginInfo previous>>
><<storyViewer pluginInfo next>>
><<storyViewer pluginInfo last>>
{{{
<<storyViewer pluginInfo previous label:"back">>
<<storyViewer pluginInfo next label:"forward">>
}}}
><<storyViewer pluginInfo previous label:"back">>
><<storyViewer pluginInfo next label:"forward">>
{{{
<<storyViewer pluginInfo links>>
}}}
><<storyViewer pluginInfo links>>
{{{
<<storyViewer pluginInfo timer:20 fold>>
}}}
><<storyViewer pluginInfo timer:20 fold>>
}}}
<<<
!!!!!Revisions
<<<
2011.01.24 1.3.4 in droplist onchange handler, don't clear slideshow 'started' flag (allows slideshow to continue after manual navigation)
2011.01.12 1.3.3 added config.macros.storyViewer.started (controls 'autostart' for automatic presentation of multiple pages)
2011.01.11 1.3.2 use pushbutton instead of text to display slideshow timer
2011.01.11 1.3.1 code and documentation cleanup
2011.01.10 1.3.0 added slideshow (params= timer:nnn, autostart, close/fold). Added custom prompt for droplist (param= prompt:"text"). Added support for [[MatchTagsPlugin]]
2008.06.05 1.2.0 added custom story paramifier to extract story titles from tiddler links instead of using parseParams. Permits use of links from any tiddler as a story, even if it contains wiki-syntax formatting in addition to list of tiddler titles
2008.03.10 *.*.* plugin size reduction: documentation moved to [[StoryViewerPluginInfo]]
2007.12.31 1.1.0 instead of readBracketedList(), use internal tiddler.links[] to retrieve story list from tiddler content. Allows more flexible formatting of story tiddler content.
2007.12.04 *.*.* update for TW2.3.0: replaced deprecated core functions, regexps, and macros
2007.10.23 1.0.0 Initial release, split {{{<<storyViewer>>}}} macro definition from [[StorySaverPlugin]] to allow separate installation of story saving vs. story viewing features.
<<<
//{{{
/*
what it's for: defines the changeFigDir macro which takes a named parameter 'prefix' and prefixes it to the images (defined by <img> tag not [img] format). This is useful when the image hosting changes and a new URL is required.
This macro is highly specific to goljanpathology.tiddlyspot.com, as you can see below by the definitions of ISBN imgID, etc. In particular, the current tiddler must have an image ID defined by it's "id" attribute. This image ID is used to construct an image filename and attach it to the src attribute of the figure contained in the tiddler.
*/
config.options.txtSCFigurePrefix='http://axs.x10.mx';
config.macros.SCImagePrefix={
label: 'change figure directory',
handler: function(place,macroName,params,wikifier,paramString,tiddler) {
jQuery(story.getTiddler(tiddler.title)).find('img .SCimage').each(function(){
this.src=config.options.txtSCFigurePrefix+this.src;
});
}
}
//}}}
/*{{{*/
.tagged{
clear:right;
}
.tagged * {
text-align:right;
display: inline;
font-weight:normal;
font-size: 95%;
}
.tagged .button {
font-size: 95%;
}
.header .siteTitle {
color: white;
}
.fixed {
position:fixed;
}
#backstageToolbar{
color: red;
}
/* give tiddlers 3d style border and explicit background */
.tiddler {
background: [[ColorPalette::Background]];
border-right: 1px black solid;
border-bottom: 1px black solid;
padding: 0.7em;
margin-bottom: 1em;
}
#fixedMenu{
background-color: rgba(0,68,187,.3);
padding-top: 2px;
padding-bottom: 2px;
}
#fixedMenu .button {
background-color: rgba(0,68,187,.9);
color: white;
}
#fixedMenu .button:hover{
background-color: [[ColorPalette::SecondaryLight]];
color:[[ColorPalette::PrimaryDark]];
}
.topMenu br {
display: none;
}
.topMenu {
background: [[ColorPalette::PrimaryMid]];
color:white ;
padding: 3px 0px 3px 0px;
}
.topMenu .button, .topMenu .tiddlyLink, .topMenu a {
padding-left: 3px;
padding-right: 3px;
color: white;
font-size: 115%;
}
.topMenu .button:hover, .topMenu .tiddlyLink:hover {
color: [[ColorPalette::PrimaryMid]];
}
#messageArea {z-index:10000}
#backstageButton .button{font-size: 8pt;}
#backstageButton {z-index: 5000}
#backstageArea{z-index: 4999}
#backstage{z-index: 4998}
.alignright {
text-align: right;
}
.tiddler{
font-size:12pt;
}
.sectionTOC{
font-size:10pt;
}
.popup{
font-size:12pt;
background-color:#FFFFFF;
color:#000000;
}
.PA blockquote{
border:0px;
}
.viewer blockquote{
border: 0px;
padding: 0;
margin: 0;
text-align: right;
}
.PA {
color:#000000;
background-color:#FFFFFF;
}
.PA > ul{
padding-left:20px;
}
.PA ol{
padding-left:20px;
margin-left:0px;
}
.PA ol[type="1"]>ul{
padding-left:0em;
}
.PA ol[type="a"] ul{
list-style-type:none;
text-indent:-1.5em;
padding-left:1.5em;
margin-left:0px;
}
table.SCtable {
empty-cells:hide;
border-collapse:separate;
border-spacing:0px;
border:1px solid darkGray;
margin-top:20px;
background-color:#FFFFFF;
color:#000000;
}
table.SCtable *{
border:0px
}
table.SCtable .inline{
border-top: 1px solid darkGray;
padding-right:10px;
padding-left:10px;
}
table.SCtable .TH td{
background-color:lightGrey;
padding-left:10px;
}
.snapshot{
background-color:white;
}
.snapshot .toolbar,.snapshot .tagged,.snapshot .tagging,.snapshot .sectionTOC {
display:none;
}
/* a contrasting background so I can see where one tiddler ends and the other begins */
body{
background: [[ColorPalette::TertiaryLight]];
}
.header a {
color: [[ColorPalette::PrimaryMid]];
}
.header {
padding: 1em 1em 0;
font-weight:bold;
}
.header .siteSubtitle {
color: [[ColorPalette::PrimaryPale]];
}
/* prefer monospace for editing */
.editor textarea {
font-family: 'Consolas' monospace;
}
/* to clear the buttons above the title */
.editor {
margin-top: 2px;
display:inline;
width:55%
}
.editor input {
display:inline;
width:55%;
}
/* sexy tiddler titles */
.title {
font-size: 110%;
color: [[ColorPalette::PrimaryMid]];
font-family: 'Trebuchet MS' sans-serif;
display:inline;
}
/* more subtle tiddler subtitle */
.subtitle {
padding:0px;
margin:0px;
padding-left:0.5em;
font-size: 90%;
color: [[ColorPalette::TertiaryMid]];
}
.subtitle .tiddlyLink {
color: [[ColorPalette::TertiaryMid]];
}
/* don't want any background color for headings */
h1,h2,h3,h4,h5,h6 {
background: [[ColorPalette::Background]];
color: [[ColorPalette::Foreground]];
}
h1{ font-size:108%; }
h2{ font-size:106%; }
h3{ font-size:104%; }
h4{ font-size:102%; }
h5{ font-size:100%; }
/* make options slider look nicer */
#sidebarOptions .sliderPanel {
border:solid 1px [[ColorPalette::PrimaryLight]];
}
/* the borders look wrong with the body background */
#sidebar .button {
border-style: none;
}
/* displays the list of a tiddler's tags horizontally. used in ViewTemplate */
.tagging {
float:right;
}
.tagging li.listTitle {
display:none;
}
/*
.tagging li {
display: inline;
}
.tagging ul {
margin:0px; padding:0px;
}
*/
/* this means you can put line breaks in SidebarOptions for readability */
#sidebarOptions br {
display:none;
}
/* undo the above in OptionsPanel */
#sidebarOptions .sliderPanel br {
display:inline;
}
/* horizontal main menu stuff */
#displayArea {
margin: 1em;
}
/* make it print a little cleaner */
@media print {
.topMenu {
display: none ! important;
}
/* not sure if we need all the importants */
.tiddler {
border-style: none ! important;
margin:0px ! important;
padding:0px ! important;
padding-bottom:2em ! important;
}
.tagglyTagging .button, .tagglyTagging .hidebutton {
display: none ! important;
}
.header {
visibility: hidden ! important;
}
.tagglyTagged .quickopentag, .tagged .quickopentag {
border-style: none ! important;
}
.quickopentag a.button, .miniTag {
display: none ! important;
}
}
.toolbar {
display:inline;
float:right;
}
.toolbar .command_closeTiddler,
.selected .toolbar .command_closeTiddler,
.toolbar .command_collapseTiddler,
.selected .toolbar .command_collapseTiddler,
.toolbar .command_expandTiddler,
.selected .toolbar .command_expandTiddler{
color: [[ColorPalette::PrimaryMid]];
font-weight:bold;
}
.selected .toolbar .command_closeTiddler:hover,
.selected .toolbar .command_collapseTiddler:hover,
.selected .toolbar .command_expandTiddler:hover{
color: [[ColorPalette::PrimaryMid]];
font-weight:bold;
}
.button{
font-size:12pt;
-moz-border-radius: 3px;
border-radius: 3px;
}
.buttonBlock {
display:inline-block;
margin-top:1px;
margin-bottom:1px;
}
.alignright {
text-align:right;
float:right;
clear:right;
}
/*}}}*/
<<toolbar top>><<jump view [[Jump to an open section]]>><<toolbar bottom>><html> </html> <<expandAllsymbol>><<collapseAllsymbol>><<closeAllsymbol>> <html> </html>
List of tables:
<<tagging>>
|>|bgcolor:#4c4c4c;@@color(#ccc):''3 tiddlers found matching /{{{memorizeiframe}}}/''@@|bgcolor:#4c4c4c; @@color:#ffffc8; Ver: <<version>>@@ |
|>|>|bgcolor:#999;color:#000;<<search>> <<option chkSearchTitles>> Titles <<option chkSearchText>> Text <<option chkSearchTags>>Tags <<option chkHoldSearches>> Hold |
|bgcolor:#4c4c4c; |bgcolor:#4c4c4c; ''Titles'' |bgcolor:#4c4c4c; ''Size'' |bgcolor:#4c4c4c; ''Tags'' |bgcolor:#4c4c4c; ''Modified'' |h
| 1|[[MemorizeIframe]]| 1133|iframe,killbookmark,memorize|2010.08.05|
| 2|[[MemorizeTables]]| 298|frmttable,memorize,tab|2008.10.11|
| 3|[[TutorialExperiment]]| 172|experimental,tab|2008.06.28|
|sortable|k
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TERM</b></td><td align="LEFT" valign="BOTTOM"><b>DEFINITION</b></td><td align="LEFT" valign="BOTTOM"><b>CONTRIBUTING FACTORS</b></td><td align="LEFT" valign="BOTTOM"><b>SIGNIFICANCE</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pao<sub>2</sub> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pressure keeping O<sub>2</sub> dissolved in the plasma of arterial blood (0.003 × Pao<sub>2</sub>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Percentage of O<sub>2</sub> in inspired air, atmospheric pressure, normal O<sub>2</sub> exchange in lungs </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Reduced in hypoxemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Driving force for movement of O<sub>2</sub> from capillaries into tissue by diffusion </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sao<sub>2</sub> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Average percentage of O<sub>2</sub> bound to Hb </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pao<sub>2</sub> and valence of heme iron in each of the four heme groups </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sao<sub>2</sub> < 80% produces cyanosis of skin and mucous membranes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fe<sup>2+</sup> binds to O<sub>2</sub>; Fe<sup>3+</sup> does not </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> O<sub>2</sub> content </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Total amount of O<sub>2</sub> carried in blood </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hb concentration in RBCs (most important factor), Pao<sub>2</sub>, Sao<sub>2</sub> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hb is the most important carrier of O<sub>2</sub> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hb concentration determines total amount of O<sub>2</sub> delivered to tissue </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> </td></tr></tbody></table><a name=""></a> <br>Fe<sup>2+</sup>, ferrous iron; Fe<sup>3+</sup>, ferric iron; Hb, hemoglobin; O<sub>2</sub>, oxygen; Pao<sub>2</sub>, partial pressure of arterial oxygen; Sao<sub>2,</sub> arterial oxygen saturation.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>SUBSTANCE</b></td><td align="LEFT" valign="BOTTOM"><b>CLINICAL SIGNIFICANCE</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Endogenous Accumulations</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bilirubin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Kernicterus (see <span>[[Fig. 15-5|Figure 15-5]]</span>): fat-soluble unconjugated bilirubin derived from Rh hemolytic disease of newborn; bilirubin enters basal ganglia nuclei of brain, causing permanent damage. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cholesterol </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Xanthelasma (see <span>[[Fig. 9-2B|Figure 9-2]]</span>): yellow plaque on eyelid; cholesterol in macrophages </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Atherosclerosis (see <span>[[Fig. 9-4|Figure 9-4]]</span>): cholesterol-laden smooth muscle cells and macrophages (i.e., foam cells); components of fibrofatty plaques </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glycogen </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diabetes mellitus: increased glycogen in proximal renal tubule cells (cells are insensitive to insulin and become overloaded with glycogen) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Von Gierke's glycogenosis: deficiency of glucose-6-phosphatase; glycogen excess in hepatocytes and renal tubular cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hematin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Melena: when blood is exposed to gastric acid, Hb is converted to a black pigment called hematin, which is responsible for black, tarry stools called melena, a sign of an upper GI bleed. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemosiderin and ferritin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Iron overload disorders (e.g., hemochromatosis; see <span>[[Fig. 18-11|Figure 18-11]]</span>): excess hemosiderin (breakdown product of ferritin) deposition in parenchymal cells, leading to FR damage and organ dysfunction (e.g., cirrhosis); increase in serum ferritin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pulmonary congestion: in left-sided heart failure there is pulmonary hemorrhage with phagocytosis of RBCs by alveolar macrophages. Hemosiderin is the breakdown product of RBC degradation in the macrophage (called "heart failure" cells). Responsible for rusty-colored sputum. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Iron deficiency (see <span>[[Fig. 11-11|Figure 11-11]]</span>): decrease in ferritin and hemosiderin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anemia of chronic disease: increase in ferritin and hemosiderin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Melanin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Addison's disease (see <span>[[Fig. 22-21|Figure 22-21]]</span>): destruction of the adrenal cortex; hypocortisolism leads to an increase in ACTH (melanocyte-stimulating properties) causing excess synthesis of melanin and diffuse pigmentation of the skin and mucosal membranes. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protein </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Amyloid (see <span>[[Figs. 3-6|Figure 3-6]]</span>, <span>[[3-7|Figure 3-7]]</span>): derives from different proteins (e.g., light chains, amyloid precursor protein). Stains red with Congo red and when polarized has apple green birefringence. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Triglyceride </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fatty liver (see <span>[[Fig. 1-8|Figure 1-8]]</span>): triglyceride in hepatocytes pushes the nucleus to the periphery. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Exogenous Accumulations</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anthracotic pigment (see <span>[[Fig. 16-18|Figure 16-18]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Coal worker's pneumoconiosis: phagocytosis of black anthracotic pigment (coal dust) by alveolar macrophages ("dust cells") </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lead </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lead poisoning: lead deposits in nuclei of proximal renal tubular cells (acid-fast inclusion) contribute to nephrotoxic changes in the proximal tubule. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>ACTH, adrenocorticotropic hormone; FR, free radical; GI, gastrointestinal.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CLASSIFICATION</b></td><td align="LEFT" valign="BOTTOM"><b>CAUSES</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Blood loss </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastrointestinal loss </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Meckel's diverticulum (older children) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> PUD (most common cause in adult men) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastritis (e.g., NSAID) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hookworm infestation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Polyps/colorectal cancer (most common cause in adults > 50 years of age); positive stool for blood </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Menorrhagia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause in women < 50 years of age </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased utilization </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pregnancy/lactation </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Daily iron requirement in pregnancy is 3.4 mg and 2.5-3 mg in lactation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Net loss of 500 mg of iron if <i>not</i> on iron supplements </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infants/children </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Iron required for tissue growth and expansion of blood volume </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased intake </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prematurity </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of iron each day fetus is not in utero </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Blood loss from phlebotomy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infants/children </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of iron deficiency in young children </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Elderly </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Restricted diets with little meat (lack of heme iron) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased absorption </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Celiac sprue<br>Post-gastric surgery </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absence of villous surface in the duodenum<br>Rapid transit; absent acid, which helps in iron reabsorption </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Microangiopathic hemolytic anemia<br>PNH </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic loss of Hb in urine leads to iron deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>Hb, hemoglobin; PNH, paroxysmal nocturnal hemoglobinuria; PUD, peptic ulcer disease.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TEST</b></td><td align="LEFT" valign="BOTTOM"><b>IRON DEFICIENCY</b></td><td align="LEFT" valign="BOTTOM"><b>ANEMIA OF CHRONIC DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>α-THAL/β-THAL MINOR</b></td><td align="LEFT" valign="BOTTOM"><b>LEAD POISONING</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> MCV </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum iron </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> TIBC </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Percent saturation </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum ferritin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> RDW </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> RBC count </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hb electrophoresis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> α-Thal trait: normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> - </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ringed sideroblasts </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> None </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> None </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> None </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Coarse basophilic stippling </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> None </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> None </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> None </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> </td></tr></tbody></table><a name=""></a> <br>Hb, hemoglobin; MCV, mean corpuscular volume; RDW, red blood cell distribution width; Thal, thalassemia; TIBC, total iron-binding capacity.
</html>
<html><sub>12</sub> DEFICIENCY<table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CLASSIFICATION</b></td><td align="LEFT" valign="BOTTOM"><b>CAUSES</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased intake </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pure vegan diet </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Breast-fed infants of pure vegans may develop deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malnutrition </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May occur in elderly patients </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malabsorption </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ Intrinsic factor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autoimmune destruction of parietal cells (i.e., pernicious anemia) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ Gastric acid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cannot activate pepsinogen to release vitamin B<sub>12</sub> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ Intestinal reabsorption </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Crohn's disease or celiac disease involving terminal ileum (destruction of absorptive cells) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bacterial overgrowth (bacterial utilization of available vitamin B<sub>12</sub>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fish tapeworm </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic pancreatitis (cannot cleave off R-binder) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased utilization </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pregnancy/lactation </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Deficiency is more likely in a pure vegan </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CLASSIFICATION</b></td><td align="LEFT" valign="BOTTOM"><b>CAUSES</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased intake </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malnutrition </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased intake most common cause of folate deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infants/elderly </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic alcoholics </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Goat milk </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malabsorption </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Celiac disease<br>Bacterial overgrowth </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Deficiency usually occurs in association with other vitamin deficiencies (fat and water soluble) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drug inhibition </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 5-Fluorouracil </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibits thymidylate synthase </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Methotrexate, trimethoprim-sulfamethoxazole </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibit dihydrofolate reductase </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Phenytoin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibits intestinal conjugase </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oral contraceptives, alcohol </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibit uptake of monoglutamate in jejunum </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alcohol also inhibits the release of folate from the liver. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased utilization </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pregnancy/lactation </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased utilization of folate in DNA synthesis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Disseminated malignancy </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Severe hemolytic anemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr></tbody></table><a name=""></a>
</html>
<html><sub>12</sub> AND FOLATE DEFICIENCIES<table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>LABORATORY/CLINICAL FINDING</b></td><td align="LEFT" valign="BOTTOM"><b>PERNICIOUS ANEMIA</b></td><td align="LEFT" valign="BOTTOM"><b>OTHER VITAMIN B<sub>12</sub> DEFICIENCIES</b></td><td align="LEFT" valign="BOTTOM"><b>FOLATE DEFICIENCY</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Achlorhydria </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autoantibodies </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic atrophic gastritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastric carcinoma risk </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> None </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> None </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypersegmented neutrophils </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mean corpuscular volume </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neurologic disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> None </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pancytopenia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Plasma homocysteine </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum gastrin level </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urine methylmalonic acid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CLASSIFICATION</b></td><td align="LEFT" valign="BOTTOM"><b>EXAMPLES AND DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Idiopathic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Approximately 50-70% of cases are idiopathic </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drugs </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common known cause of aplastic anemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dose-related causes are usually reversible (e.g., alkylating agents) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Idiosyncratic reactions are frequently irreversible (e.g., chloramphenicol) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chemical agents </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Toxic chemicals in industry and agriculture (e.g., benzene, insecticides-DDT, parathion) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infection </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May involve all hematopoietic cell lines (pancytopenia) or erythroid cell line alone (pure RBC aplasia) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Examples-EBV; CMV; parvovirus; non-A, non-B hepatitis, HCV </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Physical agents </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Whole-body ionizing radiation (therapeutic or nuclear accident) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Miscellaneous </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thymoma (may be associated with pure RBC aplasia) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Paroxysmal nocturnal hemoglobinuria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>CMV, cytomegalovirus; EBV, Epstein-Barr virus; HCV, hepatitis C.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE OF IMMUNE HEMOLYTIC ANEMIA</b></td><td align="LEFT" valign="BOTTOM"><b>EXAMPLES</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> Autoimmune </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Warm antibodies (IgG) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary or idiopathic (no underlying cause) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secondary (e.g., SLE) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cold antibodies (IgM) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary or idiopathic </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secondary </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mycoplasma pneumoniae (anti-I antibodies) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infectious mononucleosis (anti-i antibodies) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic lymphocytic leukemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Warm and cold immune hemolytic anemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drug-induced </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drug adsorption (e.g., penicillin): IgG antibody directed against the drug attached to the RBC membrane </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Immunocomplex (e.g., quinidine): drug-IgM immunocomplex deposits on the RBC causing intravascular hemolysis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autoantibody induction (e.g., α-methyldopa): drug alters Rh antigens on RBCs causing synthesis of autoantibodies against Rh antigens </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alloimmune </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemolytic transfusion reaction (refer to <span macro="tag [[15 Immunohematology Disorders]] [[Chapter 15]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ABO hemolytic disease of newborn (refer to <span macro="tag [[15 Immunohematology Disorders]] [[Chapter 15]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rh hemolytic disease of newborn (refer to <span macro="tag [[15 Immunohematology Disorders]] [[Chapter 15]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>SLE, systemic lupus erythematosus.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPES</b></td><td align="LEFT" valign="BOTTOM"><b>EXAMPLES</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> Microangiopathic </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelet thrombi </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemolytic uremic syndrome (refer <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thrombotic thrombocytopenic purpura (refer <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fibrin thrombi </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Disseminated intravascular coagulation (refer <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HELLP syndrome: H, hemolytic anemia; EL, elevated transaminases; LP, low platelets; associated with preeclampsia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macroangiopathic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aortic stenosis (most common cause) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prosthetic heart valves </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>ANEMIA</b></td><td align="LEFT" valign="BOTTOM"><b>PATHOGENESIS</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>Reticulocytosis < 3%</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute blood loss </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of whole blood </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Initial Hb and Hct normal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infusion of normal saline uncovers anemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Signs of volume depletion (e.g., absolute neutrophilic leukocytosis) commonly present; positive tilt test (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Early iron deficiency </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased iron stores </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normocytic <i>before</i> microcytic </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Iron studies abnormal (↓ serum ferritin) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Early ACD </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Iron trapped in macrophages by hepcidin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normocytic <i>before</i> microcytic<br>Iron studies abnormal (↑ serum ferritin) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aplastic anemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Suppression or deficiency of myeloid stem cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pancytopenia<br>Hypocellular marrow </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic renal failure </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Deficiency of EPO </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Presence of burr cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>Reticulocytosis ≥ 3%</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hereditary spherocytosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> AD disorder<br>Defect in ankyrin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased osmotic fragility<br>Treat with splenectomy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hereditary elliptocytosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> AD disorder<br>Defect in spectrin and band 4.1 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Elliptocytes > 25% </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Paroxysmal nocturnal hemoglobinuria </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of anchor for DAF in myeloid stem cell<br>Complement destruction of hematopoietic cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pancytopenia<br>Positive sugar water test (screen) and acidified serum test (confirmatory test) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Detect defect on hematopoietic cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sickle cell anemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> AR disorder </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HbAS: HbA 55-60%; HbS 40-45% </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Valine substitution for glutamic acid β-globin chain </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HbSS: HbS 90-95%; HbF 5-10%; no HbA </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> G6PD deficiency </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> XR disorder<br>Deficiency GSH causes oxidant damage to Hb and RBC membrane<br>Intravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Heinz body preparation: screen during active hemolysis<br>Enzyme assay: confirmatory test when hemolysis subsides </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pyruvate kinase deficiency </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> AR disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ 2,3-BPG right shifts OBC </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ ATP synthesis<br>Extravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dehydrated RBCs with thorny projections (echinocytes) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute blood loss </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of whole blood </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ Hb, Hct, RBC count </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Reticulocytosis 5-7 days </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Warm AIHA </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IgG with or without C3b </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Positive direct Coombs' test </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> SLE most common cause </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cold AIHA </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IgM with C3b </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Association with <i>Mycoplasma pneumoniae</i>; EBV </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extravascular or intravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Positive direct Coombs' test </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drug-induced immune hemolytic anemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drug hapten: penicillin<br>Extravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Positive direct Coombs' test </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Immunocomplex: quinidine Intravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autoantibody: methyldopa Extravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alloimmune hemolytic anemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antibodies against foreign RBC antigens </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemolytic transfusion reaction<br>ABO and Rh HDN </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Positive direct Coombs' test </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Micro- and macroangiopathic hemolytic anemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mechanical destruction of RBCs with formation of schistocytes<br>Intravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Calcific aortic stenosis most common cause<br>Chronic hemoglobinuria causes iron deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malaria </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmitted by female <i>Anopheles</i> mosquito<br>Intravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rupture of RBCs corresponds with fever </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>ACD, anemia of chronic disease; AD, autosomal dominant; AIHA, autoimmune hemolytic anemia; AR, autosomal recessive; ATP, adenosine triphosphate; BPG, bisphosphoglycerate; DAF, decay accelerating factor; EBV, Epstein-Barr virus; EPO, erythropoietin; G6PD, glucose-6-phosphate dehydrogenase; GSH, glutathione; Hb, hemoglobin; HbAS, sickle cell trait; HbSS, homozygous for sickle cell disease; Hct, hematocrit; OBC, oxygen-binding curve; Rh HDN, Rhesus hemolytic disease of the newborn; SLE, systemic lupus erythematosus; XR, X-linked recessive.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>POLYCYTHEMIA</b></td><td align="LEFT" valign="BOTTOM"><b>RBC MASS</b></td><td align="LEFT" valign="BOTTOM"><b>PLASMA VOLUME</b></td><td align="LEFT" valign="BOTTOM"><b>Sa<span style="font-variant:small-caps;">o</span><sub>2</sub></b></td><td align="LEFT" valign="BOTTOM"><b>EPO</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Polycythemia vera </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Appropriate polycythemia (e.g., COPD, cyanotic congenital heart disease) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inappropriate polycythemia: ectopic EPO e.g., renal cell carcinoma) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Relative polycythemia (e.g., volume depletion) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> </td></tr></tbody></table><a name=""></a> <br>COPD, chronic obstructive pulmonary disease; EPO, erythropoietin; Sa<span style="font-variant:small-caps;">o</span><sub>2</sub>, oxygen saturation.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CLASS</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> M0: Minimally differentiated AML </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No Auer rods </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> M1: AML without differentiation: 20% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rare Auer rods </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> M2: AML with maturation </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common type (30-40% of cases). </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Auer rods present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 15-59-year-old age bracket </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> M3: Acute promyelocytic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Numerous Auer rods </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> DIC is invariably present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> t(15;17) translocation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Abnormal retinoic acid metabolism: high doses of all-trans-retinoic acid may induce remission by maturing cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> M4: Acute myelomonocytic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Auer rods uncommon </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> M5: Acute monocytic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No Auer rods </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gum infiltration </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> M6: Acute erythroleukemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bizarre, multinucleated erythroblasts </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Myeloblasts present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> M7: Acute megakaryocytic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Myelofibrosis in bone marrow </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased incidence in Down syndrome in children < 3 years old </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>DIC, disseminated intravascular coagulation.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>LEUKEMIA</b></td><td align="LEFT" valign="BOTTOM"><b>DESCRIPTION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute lymphoblastic (early pre-B type) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common leukemia in children<br>Newborn to 14 years old </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CALLA (CD10) and TdT positive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> t(12;21) offers a good prognosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic lymphocytic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Virgin B-cell leukemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Patients > 60 years old </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause generalized lymphadenopathy in same age bracket </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypogammaglobulinemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adult T cell </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HTLV-1 association </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Leukemic cells CD4 positive and TdT negative </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Skin infiltration </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lytic bone lesions with hypercalcemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hairy cell </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> B cell leukemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cytoplasmic projections </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> TRAP stain positive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Splenomegaly (site of proliferation neoplastic cells) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absence of lymphadenopathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pancytopenia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dramatic response to purine nucleosides </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>CALLA, common acute lymphoblastic leukemia antigen; HTLV, human T-cell leukemia; TdT, terminal deoxynucleotidyl transferase; TRAP, tartrate-resistant acid phosphatase.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE</b></td><td align="LEFT" valign="BOTTOM"><b>EPIDEMIOLOGY</b></td><td align="LEFT" valign="BOTTOM"><b>DESCRIPTION/IMMUNOPHENOTYPE</b></td><td align="LEFT" valign="BOTTOM"><b>CLINICAL FINDINGS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Burkitt's lymphoma (see <span>[[Fig. 13-4|Figure 13-4]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 30% of children with NHL </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> EBV relationship with t(8;14)<br>"Starry sky" appearance with neoplastic B cells (dark of night) and reactive histiocytes with phagocytic debris (stars) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>American type</i>: GI tract, para-aortic nodes<br><i>African type</i>: jaw<br>Bone marrow involvement<br>Leukemic phase common </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diffuse large B-cell lymphoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 50% of adults with NHL; elderly and childhood populations </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Derives from germinal center </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Localized disease with extranodal involvement: GI tract, brain (EBV association with AIDS) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extranodal marginal zone lymphoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Association with <i>Helicobacter pylori</i> gastritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Derives from MALT </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Low-grade malignant lymphoma of the stomach </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Follicular lymphoma (see <span>[[Fig. 13-5|Figure 13-5]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 40% of adults with NHL; elderly patients </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Derives from germinal center t(14;18) causing overexpression of <i>BCL2</i> antiapoptosis gene </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Generalized lymphadenopathy<br>Bone marrow involvement </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small lymphocytic lymphoma (SLL) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Patients usually >60 years of age </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neoplasm of small, mature B lymphocytes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Generalized lymphadenopathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> SLL if confined to lymph nodes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CLL if leukemic phase is present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> </td></tr></tbody></table><a name=""></a> <br>CLL, chronic lymphocytic leukemia; EBV, Epstein-Barr virus; GI, gastrointestinal; MALT, mucosa-associated lymphoid tissue; NHL, non-Hodgkin's lymphoma.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE</b></td><td align="LEFT" valign="BOTTOM"><b>EPIDEMIOLOGY</b></td><td align="LEFT" valign="BOTTOM"><b>CLINICAL FINDINGS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lymphocyte predominant </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 5% of cases<br>Occurs mainly in males </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Asymptomatic young male with cervical or supraclavicular nodal enlargement </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Difficult to find classic RS cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> L and H variants present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Best survival statistics </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nodular sclerosing (see <span>[[Fig. 13-7|Figure 13-7]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 60% of cases<br>Occurs mainly in females </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Usually involves anterior mediastinal nodes (seen on chest x-ray) and either cervical or supraclavicular nodes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> RS cells infrequent </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lacunar cells present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Collagen separates nodular areas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mixed cellularity </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 30% of cases </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> RS cells numerous; mononuclear variants </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Men >. 50 years of age </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ Eosinophils, plasma cells, histiocytes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Strong Epstein-Barr virus association </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lymphocyte depletion </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 5% of cases </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most aggressive HL </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Men > 50 years of age </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> RS cells frequent </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Poorest survival statistics </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>RS, Reed-Sternberg.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> MGUS </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common monoclonal gammopathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small IgG M spike in elderly patients </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Plasma cells < 3% in bone marrow </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No BJ protein </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for developing multiple myeloma, Waldenstrom's macroglobulinemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Solitary skeletal plasmacytoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bone sites: vertebra, ribs, pelvis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Slight increase in monoclonal protein </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No plasmablasts in bone marrow </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No BJ protein </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 75% develop multiple myeloma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extramedullary plasmacytoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sites: upper respiratory tract (nasopharynx, sinuses, larynx) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Slight increase in monoclonal protein </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absence of malignant plasma cells in the bone marrow </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absence of BJ protein </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small percentage may develop multiple myeloma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lymphoplasmacytic lymphoma (Waldenström's macroglobulinemia) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neoplastic lymphoplasmacytoid B cells<br>Elderly male-dominant disease<br>Main risk factor is MGUS </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> M spike with IgM </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> BJ protein is present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Generalized lymphadenopathy (not present in myeloma) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anemia and bone marrow (no lytic lesions like myeloma), liver, and spleen involvement </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hyperviscosity syndrome due to increased IgM: retinal hemorrhages, strokes, platelet aggregation defects; plasmapheresis important to remove IgM </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Median survival, 5 years </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Heavy-chain diseases </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> M protein heavy chain <i>without</i> light chains </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absence of BJ protein </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> α-Heavy-chain disease: neoplastic infiltration of the jejunum, leading to malabsorption or localized upper respiratory tract disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> γ-Heavy-chain disease: presents as a lymphoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> μ-Heavy-chain disease: often associated with chronic lymphocytic leukemia or lymphoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>BJ, Bence Jones; MGUS, monoclonal gammopathy of undetermined significance.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CAUSE</b></td><td align="LEFT" valign="BOTTOM"><b>NATURE OF DEFECT</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aspirin or NSAIDs </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelet aggregation defect </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal platelet count </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibition of platelet COX, which ultimately inhibits synthesis of TXA<sub>2</sub> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bernard-Soulier syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelet adhesion defect<br>Autosomal recessive disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thrombocytopenia, giant platelets<br>Lifelong bleeding problem </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent GpIb platelet receptors for vWF </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glanzmann's disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelet aggregation defect </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lifelong bleeding problem </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal recessive disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent GpIIb-IIIa fibrinogen receptors </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent thrombosthenin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal failure </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelet aggregation defect<br>Inhibition of platelet phospholipid by toxic products </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Reversed with dialysis and desmopressin acetate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Scurvy </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vascular defect<br>Caused by vitamin C deficiency </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May cause ecchymoses and hemarthroses </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Defective collagen resulting from poor cross-linking </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thrombocytopenia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased platelet number </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased bleeding time when platelet count < 90,000 cells/mm<sup>3</sup> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Von Willebrand disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelet adhesion defect<br>Autosomal dominant disorder </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Combined platelet and coagulation factor disorder </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent or defective vWF </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased VIII:c </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>COX, cyclooxygenase; TXA<sub>2</sub>, thromboxane A<sub>2</sub>; vWF, von Willebrand factor.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute idiopathic thrombocytopenic purpura (ITP) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause thrombocytopenia in children 2-6 years of age<br>IgG antibodies directed against GpIIb-IIIa receptors (type II reaction) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Abrupt onset 1-3 weeks after a viral infection. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present with epistaxis, easy bruising, petechiae </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absence of lymphadenopathy and splenomegaly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i> varies with the platelet count </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Responds well to corticosteroids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic ITP </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of thrombocytopenia in adults </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common in women 20-40 years of age </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IgG antibodies directed against GpIIb-IIIa receptors (type II reaction) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insidious onset </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Often resistant to steroids and requires splenectomy; IV γ-globulin temporarily stops serious bleeding (IgG blocks macrophage Fc receptors) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Newborn infants of mothers with ITP may have transient thrombocytopenia due to transplacental passage of IgG antibodies </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secondary causes: SLE, HIV, lymphoproliferative diseases </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neonatal alloimmune thrombocytopenia (NAIT) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Accounts for 20% of cases of thrombocytopenia in neonates<br>Feto-maternal incompatibility for platelet specific antigens (e.g., Pl<sup>A1</sup>); Pl<sup>A1</sup> is absent from the 2% of population </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pl<sup>A1</sup>-negative mother develops IgG antibodies during pregnancy or from a previous pregnancy or transfusion </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transplacental passage of IgG antibodies targets fetal Pl<sup>A1</sup> positive platelets leading to macrophage destruction of platelets (type II hypersensitivity) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May produce petechial hemorrhages in first few days of life or CNS hemorrhages in severe cases </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Post-transfusion purpura </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primarily occurs in multiparous women </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Patient receiving blood has antibodies against Pl<sup>A1</sup> or other platelet antigens that are present on donor platelets </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Severe thrombocytopenia with destruction of donor and patient platelets occurs 7-10 days after a blood transfusion </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Heparin-induced thrombocytopenia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of thrombocytopenia in hospitalized patients </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macrophage removal of platelets surfaced by IgG antibody directed against heparin attached to PF4 (type II hypersensitivity) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs 5-14 days after Rx; must stop heparin; release of PF4 (anti-heparin factor) after platelet destruction may result in vessel thrombosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thrombotic thrombocytopenic purpura (TTP) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs in adult females<br>Acquired or genetic deficiency in vWF-cleaving metalloprotease in endothelial cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increase in circulating multimers of vWF increases platelet adhesion to areas of endothelial injury at arteriole-capillary junctions </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelets are consumed owing to production of platelet thrombi in areas of injury (<i>not</i> DIC) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Enhanced by other factors that damage endothelial cells (e.g., ticlopidine, clopidogrel, cyclosporine, oral contraceptives; hypertension, postpartum) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical pentad: fever, thrombocytopenia, renal failure, microangiopathic hemolytic anemia with schistocytes (damage by platelet thrombi), CNS deficits </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: plasma exchange; corticosteroids; vincristine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mortality rate, 10-20% </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemolytic uremic syndrome (HUS) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primarily occurs in children < 10 years old </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most often caused by endothelial damage at arteriole-capillary junction due to Shiga-like toxin of O157:H7 serotype of <i>E. coli</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Organisms proliferate in undercooked beef </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May also be caused by drugs and other infections (e.g., <i>Shigella, Salmonella</i>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical findings similar to TTP; however, CNS findings are less frequent </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bloody diarrhea in 75% of cases </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Triad: thrombocytopenia, acute renal failure, microangiopathic hemolytic anemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: plasma exchange transfusions; corticosteroids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mortality rate, 3-5% </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>DIC, disseminated intravascular coagulation; PF4, platelet factor 4; Rx, treatment; SLE, systemic lupus erythematosus; vWF, von Willebrand factor
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>PLATELET COUNT</b></td><td align="LEFT" valign="BOTTOM"><b>BLEEDING TIME</b></td><td align="LEFT" valign="BOTTOM"><b>PT</b></td><td align="LEFT" valign="BOTTOM"><b>PTT</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thrombocytopenia ITP, TTP, HUS </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Von Willebrand disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemophilia A </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> DIC </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary fibrinolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aspirin or NSAIDs </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Warfarin or heparin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> </td></tr></tbody></table><a name=""></a> <br>DIC, disseminated intravascular coagulation; HUS; hemolytic uremic syndrome; ITP, idiopathic thrombocytopenic purpura; PT, prothrombin time; PTT, partial thromboplastin time; TTP, thrombotic thrombocytopenic purpura.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>COMPONENT</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Packed RBCs </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Purpose: increase O<sub>2</sub> transport to tissues </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Packed RBCs have less volume and a higher Hct than whole blood </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Each unit of packed RBCs should raise the Hb by 1 g/dL and the Hct by 3%; lack of an increment implies a hemolytic transfusion reaction or continued blood loss in the patient </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Yersinia enterocolitica</i>, a pathogen that thrives on iron, is the most common contaminant of stored blood </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelets </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Purpose: stop medically significant bleeding related to thrombocytopenia or qualitative platelet defects (e.g., aspirin) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelets have HLA antigens and ABO antigens on their surface; however, they lack Rh antigens </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Each unit of platelets should raise the platelet count by 5000-10,000 cells/mm<sup>3</sup> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fresh frozen plasma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Purpose: treatment of multiple coagulation deficiencies (e.g., DIC, cirrhosis) or treatment of warfarin over-anticoagulation if bleeding is life-threatening </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cryoprecipitate </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Purpose: treatment of coagulation factor deficiencies involving fibrinogen and factor VIII (e.g., DIC) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cryoprecipitate contains fibrinogen, factor VIII, and factor XIII </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Desmopressin acetate is used instead of cryoprecipitate in treating mild hemophilia A and von Willebrand disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>DIC, disseminated intravascular coagulation; Hb, hemoglobin; Hct, hematocrit.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>SYMPTOM</b></td><td align="LEFT" valign="BOTTOM"><b>CAUSES/DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dyspnea </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Difficulty with breathing </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Due to stimulation of J receptors causing decrease in full inspiration </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased compliance (e.g., interstitial fibrosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased airway resistance (e.g., chronic bronchitis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chest bellows disease (e.g., obesity, kyphoscoliosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Interstitial inflammation/fluid accumulation (e.g., left-sided heart failure) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cough </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cough receptors: located at bifurcations in airways, larynx, distal esophagus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cough with a normal chest x-ray </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Postnasal discharge is the most common cause </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nocturnal cough with: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> GERD: due to acid reflux in tracheobronchial tree at night </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchial asthma: due to bronchoconstriction </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Productive cough with: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic bronchitis: due to smoking cigarettes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Typical bacterial pneumonia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchiectasis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drugs causing cough: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ACE inhibitors: inhibit degradation of bradykinin; causes mucosal swelling and irritation in tracheobronchial tree </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aspirin: causes an increase in LT C-D-E<sub>4</sub> (bronchoconstrictors) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemoptysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Coughing up blood-tinged sputum </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mechanisms: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Parenchymal necrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchial and/or pulmonary vessel damage </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic bronchitis (most common cause) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pneumonia, bronchogenic carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> TB, bronchiectasis, aspergilloma (fungus living in a cavitary lesion) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>ACE, angiotensin-converting enzyme; GERD, gastroesophageal reflux disease; LT, leukotriene; TB, tuberculosis.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>SIGN</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <b>Tachypnea</b> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal respiratory rate: 14-20 breaths per minute (bpm) in adults; up to 44 bpm in children </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tachypnea: rapid shallow breathing (>20 bpm) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: restrictive lung disease; pleuritic chest pain; pulmonary embolus with infarction (key finding) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Chest Palpation</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tracheal shift </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Due to large changes in pleural fluid volume </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pressure in contralateral lung: large tension pneumothorax, large pleural effusion </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased volume in ipsilateral lung: large spontaneous pneumothorax, resorption atelectasis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vocal tactile fremitus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Palpable thrill (vibration) transmitted through chest when patient says "E" or "1, 2, 3" or "99" </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Decreased</i> vocal tactile fremitus with emphysema or asthma, with increased AP diameter from an increase in total lung capacity </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Absent</i> vocal tactile fremitus with atelectasis (collapse of airways); fluid (effusion); air (pneumothorax) in pleural space </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Increased</i> tactile fremitus (sound travels well through consolidations) with alveolar consolidation (e.g., lobar pneumonia) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Percussion </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Dull</i> percussion with pleural effusion; lung consolidation; atelectasis (no air in the alveoli) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Hyperresonant</i> percussion with pneumothorax; asthma; emphysema </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Lung Sounds</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> General breath sounds </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Origin for normal breath sounds: trachea </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mechanism: air velocity and turbulence induce vibrations in airway walls </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sites modifying breath sound: terminal airway and alveolar disease modify breath sounds; sounds heard with the stethoscope are produced in more central (hilar) regions and are altered in intensity and tonal quality as they pass through pulmonary tissue to the periphery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Site for normal airway resistance: segmental bronchi (turbulent air flow) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Site for laminar air flow: begins at the terminal bronchioles-"small airway" </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Parallel branching: increases cross-sectional area of airways; converts turbulent into laminar air flow </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Effects of inflammation of small airways (e.g., asthma, chronic bronchitis): air trapping, wheezing, increased airway resistance </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tubular breath sounds </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sound like blowing air through a tube </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tracheal breath sound: normal sound over lateral neck or suprasternal notch </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchial breath sounds: always an abnormal sound </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loud, high-pitched sound with a peculiar hollow or tubular quality </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Expiratory sounds longer than inspiratory </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Significance: consolidation (e.g., lobar/bronchopneumonia) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mechanism: bronchi must be patent and partially collapsed </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-016-g001.jpg" id=""> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with an "air bronchogram": air-filled bronchi silhouetted against airless consolidated parenchyma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vesicular breath sounds </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal breath sounds: tracheal sounds that are modified (filtered) in alveoli </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sites: most lung fields <i>except</i> trachea and central bronchi </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inspiratory-to-expiratory ratio is 3:1 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present in: normal lungs; chronic bronchitis; emphysema </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diminished in: emphysema and asthma due to increased AP diameter </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent in: pneumothorax; atelectasis; effusion </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchovesicular breath sounds </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal breath sounds heard over main bronchi<br>Abnormal if heard in lung periphery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inspiratory and expiratory breath sounds are equal in length </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adventitial sounds </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extra sounds that are normally absent in respiratory cycle </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Crackles </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Crackles: usually inspiratory </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Early and midinspiratory crackles: due to secretions in proximal large to medium-sized airways (e.g., chronic bronchitis); clear with coughing </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Late inspiratory crackles: due to reopening of distal airways partially occluded by increased interstitial pressure (e.g., interstitial fluid-pus, transudate in CHF); do <i>not</i> clear with coughing; vary from fine to coarse </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: pulmonary edema; lobar pneumonia; interstitial fibrosis (e.g., sarcoidosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wheezing </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wheezing: high-pitched musical sound usually heard in expiration; sometimes inspiration and expiration; expiration longer than inspiration </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: inflammation segmental bronchi, small airways (e.g., asthma, chronic bronchitis); pulmonary edema constricting airway (called cardiac asthma); pulmonary infarction (release of TXA<sub>2</sub> from platelets in embolus causes bronchoconstriction) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rhonchi </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rhonchi: low-pitched snoring sound heard during inspiration or expiration; due to secretions in large airways (bronchus, trachea); usually clear with coughing; common in chronic bronchitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inspiratory stridor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inspiratory stridor: high-pitched inspiratory sound; sign of upper airway obstruction </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: epiglottitis (<i>Haemophilus influenzae</i>); croup (parainfluenza virus) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inspiratory and expiratory stridor: sign of fixed upper airway obstruction (e.g., from cancer) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pleural friction rub </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pleural friction rub: two inflamed surfaces (pleural and parietal) rubbing against each other </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Timing: end of inspiration and early part of expiration </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Disappears: large effusion is present (separates inflamed surfaces); holding breath (continues with pericardial friction rub) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: pleuritis due to cancer, infarction, pneumonia, serositis (SLE) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Grunting in newborns </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Grunting in newborns: always abnormal after 24 hours; common finding in RDS </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmitted voice sounds </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchophony (sound of bronchi) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal lung: spoken syllables or numbers (e.g., 99) are <i>indistinctly heard</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alveolar consolidation: syllables/numbers heard louder and more distinctly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Whispered pectoriloquy (Latin for "voice of chest"): clear and intelligible words (e.g., patient whispering "1, 2, 3") </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Egophony (Greek for "voice of goat"): patient saying "E" sounds like "A" </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>AP, anteroposterior; bpm, breaths per minute; CHF, congestive heart failure; RDS, respiratory distress syndrome; SLE, systemic lupus erythematosus; TXA<sub>2</sub>, thromboxane A<sub>2</sub>.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>PARAMETER</b></td><td align="LEFT" valign="BOTTOM"><b>RESTRICTIVE</b></td><td align="LEFT" valign="BOTTOM"><b>OBSTRUCTIVE</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Total lung capacity </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Residual volume </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> FEV<sub>1 sec</sub> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> FVC </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> FEV<sub>1 sec</sub>/FVC </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal to increased </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pa<span style="font-variant:small-caps;">o</span><sub>2</sub> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <span style="font-variant:small-caps;">a</span>-a gradient </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br><span style="font-variant:small-caps;">a</span>-a, alveolar-arterial; FEV, forced expiratory volume; FVC, forced vital capacity.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>PATHOGEN</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Viruses</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rhinovirus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of the common cold </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmitted by hand to eye-nose contact </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Other causes of colds-coronaviruses, adenoviruses, influenza C virus, coxsackievirus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Coxsackievirus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute chest syndrome: fever with pleuritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> RSV </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common viral cause of atypical pneumonia and bronchiolitis (wheezing) in children; otitis media in older children </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs in late fall and winter </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rapid diagnosis with antigen detection in nasopharyngeal wash </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Passive immunization: palivizumab (monoclonal antibody) reduces hospitalization rates </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Parainfluenza (see <span>[[Fig. 16-10A|Figure 16-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of croup (laryngotracheobronchitis) in infants </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inspiratory stridor (upper airway obstruction) due to submucosal edema in trachea; brassy cough; signs of respiratory distress </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anterior x-ray of neck shows "steeple sign," representing mucosal edema in the trachea (site of obstruction) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchiolitis in infants </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: cold water humidifiers and aerosolized racemic epinephrine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CMV (see <span>[[Fig. 16-10B|Figure 16-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common pneumonia in immunocompromised hosts (e.g., bone marrow transplants, AIDS) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Enlarged alveolar macrophages/pneumocytes, contain basophilic intranuclear inclusions surrounded by a halo </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Influenzavirus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type A viruses are most often involved </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemagglutinins bind virus to cell receptors in the nasal passages </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neuraminidase dissolves mucus and facilitates release of viral particles </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Influenza A: worldwide epidemics; pneumonia may be complicated by a superimposed bacterial pneumonia (usually <i>Staphylococcus aureus</i>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Influenza B: causes major outbreaks </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antigen drift: minor mutation; does <i>not</i> require new vaccine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antigen shift: major mutation in hemagglutinin or neuraminidase; new vaccine required </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical: fever, headache, cough, myalgias, chest pain </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vaccination: mandatory for people > 65 years old, people with chronic illnesses </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: neuraminidase inhibitors zanamivir, oseltamivir </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associations: Reye syndrome with salicylate ingestion; Guillain-Barré syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rubeola </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fever, cough, conjunctivitis, and excessive nasal mucus production </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Koplik spots in the mouth <i>precede</i> onset of the rash </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Warthin-Finkeldey multinucleated giant cells are a characteristic finding </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> SARS </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infects lower respiratory tract and then spreads systemically </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> First transmitted to humans through contact with masked palm civets (China) and then from human-to-human contact through respiratory secretions (e.g., hospitals, families) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Develop severe respiratory infection </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnose with viral detection by PCR assay or detection of antibodies </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hantavirus pulmonary syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmission: inhalation of urine/feces from deer mice in Southwestern United States </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pulmonary syndrome: ARDS, hemorrhage, renal failure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: detect viral RNA in lung tissue </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No effective treatment </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> High mortality rate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Bacteria</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Chlamydia</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Chlamydophilia pneumoniae</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Second most common cause of atypical pneumonia<br>Seroepidemiologic association with coronary artery disease<br><i>Treatment</i>: doxycycline </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Chlamydia trachomatis</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Newborn pneumonia (passage through birth canal)<br>Afebrile, staccato cough (choppy cough), conjunctivitis, wheezing<br><i>Treatment</i>: erythromycin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Mycoplasma</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of atypical pneumonia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>M. pneumoniae</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common in adolescents and military recruits (closed spaces) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insidious onset with low-grade fever </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complications: bullous myringitis, cold autoimmune hemolytic anemia due to anti-I-IgM antibodies. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: erythromycin; azithromycin; clarithromycin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cold agglutinins in blood </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Coxiella burnetii</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Usually transmitted without a vector </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted by dairy farmers, veterinarians </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with the birthing process of infected sheep, cattle, and goats, and handling of milk or excrement </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Atypical pneumonia, myocarditis, granulomatous hepatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: doxycycline </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Streptococcus pneumoniae</i> (see <span>[[Fig. 16-9A|Figure 16-9]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive lancet-shaped diplococcus<br>Most common cause of typical community-acquired pneumonia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rapid onset, productive cough, signs of consolidation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urine antigen test excellent screen </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: penicillin G; amoxicillin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Staphylococcus aureus</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive cocci in clumps </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Yellow sputum </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Commonly superimposed on influenza pneumonia and measles pneumonia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Major lung pathogen in cystic fibrosis and IV drug abusers </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemorrhagic pulmonary edema, abscess formation, and tension pneumatocysts (intrapleural blebs), which may rupture and produce a tension pneumothorax. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: TMP-SMX </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Corynebacterium diphtheriae</i> (see <span>[[Fig. 16-10C|Figure 16-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive rod<br>Toxin inhibits protein synthesis by ADP-ribosylation of elongation factor 2 involved in protein synthesis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Toxin also impairs β-oxidation of fatty acids in the heart </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Toxin-induced pseudomembranous inflammation produces shaggy gray membranes in the oropharynx and trachea; toxic myocarditis (death) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: erythromycin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Bacillus anthracis</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive rod </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Habitat: soil </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Capsule inhibits phagocytosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Exotoxins: edema factor (activates adenylate cyclase); lethal factor (inhibits a signal transduction protein involved in cell division); protective antigen (assists entry of above toxins into cells) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmission: direct contact with animal skins or products (most commonly sheep and cattle) and entry of the organisms through abrasions or cuts; inhalation (use in germ warfare) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cutaneous anthrax (90-95% of cases): occurs through direct contact with infected or contaminated animal products; resembles insect bite but eventually swells to form a black scab, or eschar, with a central area of necrosis ("malignant pustule"); if untreated, death occurs in 20% of patients </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pulmonary anthrax: "first sign of the disease is death"; inhalation of spores present in contaminated hides or germ warfare; necrotizing pneumonia, meningitis, pronounced splenomegaly, and dissemination throughout the rest of the body </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prevention: vaccine available for high-risk patients; e.g., veterinarians, soldiers entering developing countries </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ciprofloxacin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Actinomyces israeli</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive filamentous bacteria; strict anaerobe; normal flora in tonsils and adenoids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces draining sinuses in the jaw, chest cavity, and abdomen; pus contains sulfur granules (yellow specks) that contain the bacteria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ampicillin or penicillin G </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Nocardia asteroides</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive filamentous bacteria; strict aerobe; partially acid-fast </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces granulomatous microabscesses in the lungs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Frequently disseminates to the CNS and kidneys </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: TMP-SMX </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Bordetella pertussis</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative rod </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pili attach to cilia in upper respiratory tract; toxin stimulates adenylate cyclase, which catalyzes the addition of ADP-ribose to the inhibitory subunit of the G protein complex; toxin also produces absolute lymphocytosis (normal-appearing lymphocytes) often in leukemoid reaction range </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces whooping cough, transmitted by droplet infection </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Catarrhal phase: lasts 1-2 weeks; mild coughing, rhinorrhea, conjunctivitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Paroxysmal coughing phase: lasts 2-5 weeks; characteristic 4-5 coughs in succession on expiration followed by an inspiratory whoop; absolute lymphocytosis (20,000-50,000 cells/mm<sup>3</sup>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Convalescence phase: lasts 1-2 weeks; slow decline in coughing and lymphocytosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complications: hemorrhage into skin, conjunctiva, bronchus, brain from coughing; otitis media; meningoencephalitis (10%); rectal prolapse from coughing; pneumonia (most common cause of death in children < 3 years old; children < 1 year old have no protection from mother's immunoglobulins) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: nasopharyngeal swabs using special cough plate; direct immuno-fluorescence of swab material </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: erythromycin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Haemophilus influenzae</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative rod </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common cause of sinusitis, otitis media, conjunctivitis ("pinkeye") </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inspiratory stridor may be due to acute epiglottitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Swelling of epiglottis produces "thumbprint sign" on lateral x-ray of the neck </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common bacterial cause of acute exacerbation of COPD </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: cefotaxime; ceftriaxone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Moraxella catarrhalis</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative diplococcus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common cause of typical pneumonia, especially in the elderly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Second most common pathogen causing acute exacerbation of COPD </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common cause of chronic bronchitis, sinusitis, otitis media </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: amoxicillin-clavulanate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Pseudomonas aeruginosa</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Green sputum (pyocyanin) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Water-loving bacteria most often transmitted by respirators </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of nosocomial pneumonia and death due to pneumonia in cystic fibrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pneumonia often associated with infarction due to vessel invasion </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: antipseudomonal beta-lactam + aminoglycoside + antipseudomonal quinolone or macrolide </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Klebsiella pneumoniae</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative fat rod surrounded by a mucoid capsule </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common gram-negative organism causing lobar pneumonia and typical pneumonia in elderly patients in nursing homes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common cause of pneumonia in alcoholics; however, <i>S. pneumoniae</i> is still the most common pneumonia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Atypical pneumonia associated with blood-tinged, thick, mucoid sputum </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lobar consolidation and abscess formation are common </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ceftriaxone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Legionella pneumophila</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative rod (requires IF stain or Dieterle silver stain to identify in tissue) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antigens can also be detected in urine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Water-loving bacterium (water coolers; mists in produce section of grocery stores; outdoor restaurants in summer; rain forests in zoos) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Risk factors: alcoholic, smoker, immunosuppression </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pneumonia associated with high fever, dry cough, flu-like symptoms </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May produce tubulointerstitial disease with destruction of the JG apparatus leading to hyporeninemic hypoaldosteronism (type IV renal tubular acidosis-hyponatremia, hyperkalemia, metabolic acidosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urine antigen test excellent screen </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: fluoroquinolone; azithromycin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Yersinia pestis</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative rod </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cause of plague </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmitted by bite of rat flea; primary reservoir for bacteria are ground squirrels in the Southwest </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Also transmitted person-to-person by droplet infection </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macrophages cannot kill bacteria due to protection by V and W antigens </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Three types of disease: bubonic (most common), pneumonic (transmitted by aerosol), septicemic </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bubonic type: bite by rat flea that has recently bitten an infected ground squirrel; infected lymph nodes enlarge (usually in the groin), mat together, and drain to the surface (buboes) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pneumonic type: gentamicin + doxycycline </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bubonic type: gentamicin or streptomycin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Systemic Fungi</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Cryptococcus neoformans</i> (see <span>[[Fig. 16-10D|Figure 16-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Budding yeast with narrow-based buds; surrounded by a thick capsule. Found in pigeon excreta (around buildings, outside office windows, under bridges) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary lung disease (40%): granulomatous inflammation with caseation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: fluconazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Aspergillus fumigatus</i> (see <span>[[Fig. 16-10E|Figure 16-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fruiting body and narrow-angled (<45 degrees), branching septate hyphae </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aspergilloma: fungus ball (visible on x-ray) that develops in a preexisting cavity in the lung (e.g., old TB site); cause of massive hemoptysis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Allergic bronchopulmonary aspergillosis: type I and type III hypersensitivity reactions; IgE levels increased; eosinophilia. Intense inflammation of airways and mucus plugs in terminal bronchioles. Repeated attacks may lead to bronchiectasis and interstitial lung disease; treatment with corticosteroids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vessel invader with hemorrhagic infarctions and a necrotizing bronchopneumonia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: voriconazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Mucor species</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wide-angled hyphae (>45 degrees) without septa </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical settings: diabetes, immunosuppressed patients </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vessel invader and produces hemorrhagic infarcts in the lung </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Invades the frontal lobes in patients with diabetic ketoacidosis (rhinocerebral mucormycosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: amphotericin B </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Coccidioides immitis</i> (see <span>[[Fig. 16-10F|Figure 16-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Spherules with endospores in tissues </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted by inhaling arthrospores in dust while living or passing through arid desert areas in the Southwest (valley fever); increased after earthquakes (increased dust) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Flu-like symptoms and erythema nodosum (painful nodules on lower legs; inflammation of subcutaneous fat) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Granulomatous inflammation with caseous necrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: usually self-limited; if severe: itraconazole or fluconazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Histoplasma capsulatum</i> (see <span>[[Fig. 16-10G, H|Figure 16-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common systemic fungal infection </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Endemic in Ohio and central Mississippi river valleys </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhalation of microconidia in dust contaminated with excreta from bats (increased incidence in cave explorers, spelunkers), starlings, or chickens (common in chicken farmers) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Granulomatous inflammation with caseous necrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Yeast forms are present in macrophages </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Simulates TB lung disease; produces coin lesions, consolidations, miliary spread, and cavitation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Marked dystrophic calcification of granulomas; most common cause of multiple calcifications in the spleen </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: usually self-limited; if severe, itraconazole or amphotericin B </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Blastomyces dermatitidis</i> (see <span>[[Fig. 16-10I|Figure 16-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Yeasts have broad-based buds and nuclei </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs in Great Lakes region, central, and southeastern United States </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Male dominant disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces skin and lung disease; skin lesions simulate squamous cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Granulomatous inflammation with caseous necrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: itraconazole or amphotericin B </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Pneumocystis jiroveci</i> (see <span>[[Fig. 3-3|Figure 3-3]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cysts and trophozoites present; cysts attach to type I pneumocytes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primarily an opportunistic infection; occurs when CD4 count < 200 cells/mm<sup>3</sup>. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common initial AIDS-defining infection </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Patients develop fever, dyspnea, and severe hypoxemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diffuse intra-alveolar foamy exudates with cup-shaped cysts best visualized with silver or Giemsa stains </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chest x-ray shows diffuse alveolar and interstitial infiltrates </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: TMP-SMX given prophylactically when CD4 counts < 200 cells/mm<sup>3</sup> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>ARDS, acute respiratory distress syndrome; CMV, cytomegalovirus; COPD, chronic obstructive pulmonary disease; IF, immunofluorescent; JG, juxtaglomerular; PCR, polymerase chain reaction; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; TB, tuberculosis; TMP-SMX, trimethoprim-sulfamethoxazole.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>PARAMETER</b></td><td align="LEFT" valign="BOTTOM"><b>EMPHYSEMA</b></td><td align="LEFT" valign="BOTTOM"><b>CHRONIC BRONCHITIS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pa<span style="font-variant:small-caps;">o</span><sub>2</sub> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal to decreased </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> pH </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal to increased </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cyanosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Habitus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stocky </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cor pulmonale </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rare </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Onset of hypoxemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Late </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Early </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Onset of dyspnea </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Early </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Late </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE OF TUMOR OR DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>LOCATION IN LUNG</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma (see <span>[[Fig. 16-30E and F|Figure 16-30]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> More common in women<br>Some types are associated with cigarette smoking </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Scar carcinomas: develop in scars (e.g., old tuberculous granuloma); no relationship to smoking </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchioloalveolar carcinoma: derives from Clara cells (nonciliated epithelium); malignant cells spread along alveolar walls (look like pegs); radiologically mimic lobar pneumonia; no relationship to smoking </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Squamous cell carcinoma (see <span>[[Fig. 16-30A|Figure 16-30]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Central </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> More common in men<br>Strong association with cigarette smoking<br>Tend to cavitate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May ectopically secrete PTH-related protein (peptide) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small cell carcinoma (see <span>[[Fig. 16-30B|Figure 16-30]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Central </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> More common in men<br>Strong association with cigarette smoking </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Arise from neuroendocrine cells (Kulchitsky cells) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rapidly growing cancer that metastasizes early </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May ectopically secrete ADH or ACTH </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Large cell carcinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Undifferentiated cancer that metastasizes early; no relationship to smoking </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchial carcinoid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Central </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Low-grade cancer of neuroendocrine origin; no association with smoking; present at a mean age of 55 years old; most common primary lung tumor in children; ∼ 20% locally metastasize; present with hemoptysis (most common), cough, carcinoid syndrome (<1%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Carcinoma metastatic to the lung (see <span>[[Figs. 16-31|Figure 16-31]]</span> and <span>[[16-32|Figure 16-32]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Multifocal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> More common than primary cancer<br>Sites of metastasis: parenchyma (most common), pleura/pleural space, endobronchial mucosa, lymphatics (causes dyspnea) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchial hamartoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral (90%) Central (10%) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Non-neoplastic proliferation of cartilage and adipose tissue<br>Appears as solitary "coin" lesion on chest radiograph; popcorn calcifications </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>ACTH, adrenocorticotropic hormone; ADH, antidiuretic hormone; PTH, parathyroid hormone.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>COMPONENT</b></td><td align="LEFT" valign="BOTTOM"><b>TRANSUDATE</b></td><td align="LEFT" valign="BOTTOM"><b>EXUDATE</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> PF protein/serum protein </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <0.5 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >0.5 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> PF LDH/serum LDH </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <0.6 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >0.6 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> PF LDH </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <200 U/L </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >200 U/L </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>LDH, lactate dehydrogenase; PF, pleural fluid.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>INFECTION</b></td><td align="LEFT" valign="BOTTOM"><b>PATHOGEN</b></td><td align="LEFT" valign="BOTTOM"><b>FEATURES</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>Viral</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Exudative tonsillitis (see <span>[[Fig. 17-2A|Figure 17-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Viruses: most cases </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Culture is necessary to differentiate bacterial versus viral infection </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hairy leukoplakia (see <span>[[Fig. 17-2B|Figure 17-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> EBV </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glossitis associated with bilateral white excrescences on lateral border of tongue </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pre-AIDS-defining lesion (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Herpes labialis (see <span>[[Fig. 17-2C|Figure 17-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HSV type 1 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Recurrent vesicular lesions on the lips (virus remains dormant in cranial sensory ganglia) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Reactivated by stress, sunlight, and menses </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: oral acyclovir, valacyclovir, famciclovir; topical acyclovir, penciclovir </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mumps </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Paramyxovirus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bilateral parotitis (70%) with increased serum amylase </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complications: meningoencephalitis, unilateral orchitis or oophoritis, pancreatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Herpangina </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Coxsackievirus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs in children </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Multiple vesicles or ulcers on soft palate and pharynx surrounded by erythema </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hand-foot-mouth disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Coxsackievirus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs in young children </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vesicles located in mouth and distal extremities </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>Bacterial</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cervicofacial actinomycosis (see <span>[[Fig. 17-2D|Figure 17-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Actinomyces israelii</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Draining sinus tract from facial or cervical area"Sulfur granules" in pus; contain gram-positive, branching filamentous bacteria; anaerobe </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Often follows after extraction of an abscessed tooth </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ampicillin, penicillin G </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diphtheria (see <span>[[Fig. 16-10C|Figure 16-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Corynebacterium diphtheriae</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Toxin produces "shaggy" gray pseudomembrane in posterior pharynx and upper airways </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: erythromycin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peritonsillar abscess </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Streptococcus pyogenes</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Uvula deviates to contralateral side; "hot potato" voice; foul-smelling breath </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complication due to tonsillitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: surgical drainage of pus; penicillin G or V; add clindamycin for serious invasive infections </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ludwig's angina </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Aerobic/anaerobic Streptococcus, Eikenella corrodens</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cellulitis involving the submaxillary and sublingual space; follows fascial planes and may spread into pharynx, carotid sheath, superior mediastinum<br>Causes: dental extraction (most common), trauma to floor of mouth </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: surgical drainage; clindamycin + metronidazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pharyngitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>S. pyogenes</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with tonsillitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Potential for acute rheumatic fever and glomerulonephritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: penicillin V </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Scarlet fever </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>S. pyogenes</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pharyngitis, tonsillitis, glossitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Erythrogenic toxin produces rash on skin and tongue (initially white and then strawberry colored) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for glomerulonephritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nephritogenic strains pose no risk for acute rheumatic fever </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: penicillin G or V </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sialadenitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Staphylococcus aureus</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bacterial inflammation of major salivary gland<br>Secondary to a calculus, which obstructs the duct in postoperative patients </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: oxacillin, nafcillin if methicillin susceptible; TMP/SMX if community-acquired methicillin resistant; vancomycin if methicillin resistant in hospital </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Congenital syphilis (see <span>[[Fig. 17-2E|Figure 17-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treponema pallidum</i> (spirochete) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Abnormalities involving incisors (tapered like a peg) and molar teeth (resemble mulberries)<br><i>Treatment</i>: aqueous crystalline penicillin G </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>Fungal</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oral thrush (see <span>[[Fig. 17-2F|Figure 17-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Candida albicans</i> (yeast) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May occur in neonates, immunocompromised patients (common pre-AIDS-defining lesion), diabetes mellitus, and following antibiotic therapy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: fluconazole, itraconazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>EBV, Epstein-Barr virus; HSV, herpes simplex virus; TMP/SMX, trimethoprim-sulfamethoxazole.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>FEATURE</b></td><td align="LEFT" valign="BOTTOM"><b>GASTRIC ULCERS</b></td><td align="LEFT" valign="BOTTOM"><b>DUODENAL ULCERS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Percentage of ulcer cases </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 25% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 75% </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Epidemiology </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Male/female ratio 1:1 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Male/female ratio 2:1 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Smoking does <i>not</i> cause PUD but delays healing </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Risk increased with MEN I<br>Increased risk in cirrhosis, COPD, renal failure, hyperparathyroidism </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Helicobacter pylori</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ∼ 80% of cases </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 90-95% of cases </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pathogenesis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Defective mucosal barrier due to <i>H. pylori</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Defective mucosal barrier due to <i>H. pylori</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mucosal ischemia (reduced PGE), bile reflux, delayed gastric emptying </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased acid production (increased parietal cell mass) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> BAO and MAO normal to decreased </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> BAO and MAO both increased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Location </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Single ulcer on lesser curvature of antrum (same location for cancer) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Single ulcer on anterior portion of first part of duodenum followed by single ulcer on posterior portion (danger of perforation into pancreas and pancreatitis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complications (see <span>[[Fig. 17-15|Figure 17-15]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bleeding (most commonly in left gastric artery)<br>Perforation </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bleeding (most commonly in gastroduodenal artery)<br>Perforation (air under diaphragm, pain radiates to left or right shoulder) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastric outlet obstruction, pancreatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical findings </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Epigastric pain exacerbated by eating </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Epigastric pain relieved by eating </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Endoscopy: 90-95% accuracy; must biopsy gastric ulcers (1-4% malignant) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Endoscopy: 90-95% accuracy; no need to biopsy because never malignant </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Upper GI barium study: identify 70-80% PUD </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Upper GI barium study: identify 70-80% PUD </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Treatment </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nonpharmacologic: stop smoking; avoid NSAIDs and alcohol; avoid foods causing symptoms<br>Pharmacologic: eradication of <i>H. pylori</i>; H<sub>2</sub> receptor antagonists; proton pump inhibitors; antacids<br>Surgery for resistant cases uncommon: ulcer removal with antrectomy or hemigastrectomy without vagotomy </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nonpharmacologic: stop smoking; avoid NSAIDs and alcohol; avoid foods causing symptoms<br>Pharmacologic: eradication of <i>H. pylori</i>; H<sub>2</sub> receptor antagonists; proton pump inhibitors; antacids<br>Surgery for resistant cases uncommon: highly selective vagotomy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>BAO, basal acid output; COPD, chronic obstructive pulmonary disease; GI, gastrointestinal; MAO, maximal acid output; MEN, multiple endocrine neoplasia; PGE, prostaglandin E; PUD, peptic ulcer disease.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE</b></td><td align="LEFT" valign="BOTTOM"><b>CHARACTERISTICS</b></td><td align="LEFT" valign="BOTTOM"><b>CAUSES</b></td><td align="LEFT" valign="BOTTOM"><b>SCREENING TESTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Invasive </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pathogens invade enterocytes<br>Low-volume diarrhea </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Shigella</i> spp.<br><i>Campylobacter jejuni</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fecal smear for leukocytes: positive in most cases </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diarrhea with blood and leukocytes (i.e., dysentery) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Entamoeba histolytica</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Order stool culture and stool for O&P </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secretory </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of isotonic fluid<br>High-volume diarrhea<br>Mechanisms:<br> Laxatives<br> Enterotoxins stimulate Cl<sup>-</sup> channels regulated by cAMP and cGMP<br> Serotonin increases bowel motility<br>No inflammation in bowel mucosa </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Laxatives: danger of melanosis coli (black bowel syndrome) with use of phenanthracene laxatives<br>Production of enterotoxins:<br> <i>Vibrio cholerae</i><br> Enterotoxigenic <i>E. coli</i><br>Increased serotonin: carcinoid syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fecal smear for leukocytes: negative<br>Increased 5-HIAA: carcinoid syndrome<br>Stool osmotic gap < 50 mOsm/kg </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osmotic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osmotically active substance is drawing hypotonic salt solution out of bowel<br>High-volume diarrhea<br>No inflammation in bowel mucosa </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Disaccharidase deficiency<br>"Stunned gut" in giardiasis<br>Ingestion of poorly absorbable solutes (e.g., magnesium sulfate laxatives) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fecal smear for leukocytes: negative<br>Stool osmotic gap > 100 mOsm/kg </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> </td></tr></tbody></table><a name=""></a> <br>cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; HIAA, hydroxyindoleacetic acid; O&P, ova and parasites.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>PATHOGEN</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Viruses</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cytomegalovirus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common cause of diarrhea in AIDS when CD4 T<sub>H</sub> cell count < 50-100 cells/mm<sup>3</sup> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ganciclovir </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Norwalk virus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of adult gastroenteritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nausea, vomiting, diarrhea that resolves in 12-24 hours </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occasionally can be fatal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fecal-oral transmission </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common infection on cruise ships </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: supportive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rotavirus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of childhood diarrhea; particularly occurs in winter months<br>Fecal-oral transmission </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Damages ion transport pump in small intestine; secretory diarrhea </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rotazyme test on stool establishes diagnosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rotavirus vaccine highly effective in prevention; oral vaccine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: oral hydration; nitazoxanide </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Bacteria</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Bacillus cereus</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive rod </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Food poisoning with preformed toxin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with reheated fried rice or tacos </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Self-limited </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Campylobacter jejuni</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Curved or S-shaped gram-negative rod </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Animal reservoirs: cattle, chicken, puppies (common source for children) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmission fecal-oral via contaminated water, poultry, or unpasteurized milk </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common food-borne illness and invasive enterocolitis in United States </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Invasive and secretory enterocolitis: dysentery (bloody diarrhea) with crypt abscesses and ulcers resembling ulcerative colitis; high fever and cramping abdominal pain; organisms in stool with blood and leukocytes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complications: Guillain-Barré syndrome (antibodies cross-react with neurons); hemolytic uremic syndrome; HLA-B27 positive seronegative spondyloarthropathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: azithromycin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Clostridium botulinum</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive rod </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adult food poisoning with preformed toxin (blocks release of acetylcholine release in presynaptic terminal of neuromuscular junction in autonomic nervous system; causes descending paralysis, mydriasis, dry mouth </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: trivalent antitoxin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infant food poisoning often contracted by eating spores in honey (lack protective bacteria); floppy baby with constipation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Clostridium difficile</i> (see <span>[[Figs. 2-8|Figure 2-8]]</span> and <span>[[17-18A|Figure 17-18]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive rod<br>Associated with pseudomembranous colitis; the most common cause of nosocomial diarrhea; secretory type of diarrhea </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normally present in 3% of people; carrier rate increases to >20% in hospitalized patients (related to contact with spores in environment and fecal-oral contamination) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antibiotic-induced in 65-90% of cases; antibiotics (e.g., ampicillin, quinolones, clindamycin) cause overgrowth of toxin-producing <i>C. difficile</i> in colon; toxins A and B release proinflammatory mediators and cytokines that attract neutrophils and stimulate excess fluid secretion (watery diarrhea) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pseudomembrane covers colon mucosa; composed of cellular debris, leukocytes, fibrin, and mucin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Person-to-person induced in 30% of cases </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nonspecific lab findings: neutrophilic leukocytosis with left shift; fecal leukocytes; and, decreased serum albumin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cytotoxin assay of stool has greater specificity (75-100%) than culture of stool (75-80%) for securing the diagnosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: metronidazole; vancomycin produces resistant strains </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Escherichia coli</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative rod </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ETEC: certain strains produce toxin that activate adenylate or guanylate cyclase, causing secretory diarrhea (traveler's diarrhea; accounts for 60% of cases); other causes include <i>Campylobacter</i>, <i>Salmonella</i>, <i>Shigella</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: levofloxacin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> STEC (O157:H7 serotype): contracted by eating undercooked beef </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces hemolytic uremic syndrome (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antibiotics <i>not</i> recommended; may enhance toxin release </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Mycobacterium avium-intracellulare complex (MAC)</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acid-fast rods<br>Causes diarrhea with malabsorption in AIDS (CD4 count < 50 cells/mm<sup>3</sup>)<br>Foamy macrophages in lamina propria simulate Whipple's disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Mycobacterium tuberculosis</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acid-fast organisms swallowed from primary focus in lung </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Invade Peyer's patches </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Circumferential spread in lymphatics leads to stricture formation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Salmonella</i> species </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative rod </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pathogenic <i>Salmonella: S. typhi, S. paratyphi, S. enteritidis</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Animal reservoirs: turtles, hamsters, lizards </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Salmonella enteritidis</i> enterocolitis: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Second most common food-borne illness in United States; contracted by eating raw or undercooked egg products, raw milk and milk products, and poultry or drinking contaminated water </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ciprofloxacin or levofloxacin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Typhoid fever caused by <i>S. typhi</i>: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Week 1: invades Peyer's patches and produces sepsis (blood culture best for diagnosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Week 2: diarrhea (positive stool culture); classic triad of bradycardia, neutropenia, splenomegaly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: treat if symptomatic with fluoroquinolone; antibiotics do <i>not</i> shorten the illness and may increase frequency of carrier states </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic carrier state due to gallbladder disease: cholecystectomy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Shigella dysenteriae and Shigella sonnei</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative rod </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No animal reservoirs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Highly infectious; children in day care centers; mental institutions </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mucosal ulceration, pseudomembranous inflammation in rectosigmoid, dysentery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Association with HLA-B27 positive seronegative spondyloarthropathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: treat if symptomatic with fluoroquinolone or azithromycin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Staphylococcus aureus</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive coccus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Food poisoning with preformed toxin; culture food, <i>not</i> stool </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastroenteritis occurs in 1-6 hours after eating </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Self-limited </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Vibrio cholerae</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative comma-shaped rod </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Enterotoxin stimulates adenylate cyclase in small bowel </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted from drinking contaminated water or eating contaminated seafood, especially crustacea </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: fluid replacement; glucose and sodium required in oral supplements (cotransport system for reabsorption); doxycycline or fluoroquinolone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Yersinia enterocolitica</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative coccobacillus with bipolar staining </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Enterocolitis in children; mesenteric lymphadenitis (granulomatous microabscesses) that simulates acute appendicitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Association with HLA-B27 positive seronegative spondyloarthropathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: TMP-SMX </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Protozoa</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Balantidium coli</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protozoan (ciliate); largest protozoan<br>Transmitted by ingestion of cysts in food or water </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces colonic ulcers with bloody diarrhea </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: tetracycline </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Cryptosporidium parvum</i> (see <span>[[Fig. 17-18B|Figure 17-18]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protozoan (sporozoa) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmitted by ingestion of oocysts in food or water </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Responsible for outbreaks of diarrhea in water supply (e.g., Milwaukee, Wisconsin) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of diarrhea in AIDS </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: stool antigen test (sensitivity/specificity 98%); oocysts partially acid-fast </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i> if immunocompetent: nitazoxanide (less responsive to drug if immunodeficient) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Cyclospora, Microsporidia, Isospora belli</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protozoa (sporozoa)<br>Fecal-oral transmission </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> All are common pathogens in AIDS diarrhea </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Cyclospora</i> can contaminate raspberries </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Microsporidia</i> spores <i>not</i> partially acid-fast </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Cyclospora</i> oocysts partially acid-fast </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Isospora</i> oocysts partially acid-fast </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: <i>Cyclospora</i>: TMP-SMX double strength; <i>Microsporidia</i>: albendazole; </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Isospora</i>: TMP-SMX double strength </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Entamoeba histolytica</i> (see <span>[[Fig. 17-18C|Figure 17-18]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protozoa (amoeba) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmitted by ingestion of cysts in food and water </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cysts are nonmotile and are present in formed stool; trophozoites are motile and are present in diarrhea </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces dysentery (bloody diarrhea); cysts excyst in the cecum and become trophozoites in the cecum; trophozoites release powerful histolytic agents that produce flask-shaped ulcers; trophozoites can penetrate portal vein tributaries and drain to the liver to produce a liver abscess ("anchovy paste" abscess); trophozoites can penetrate hepatic vein tributaries and produce systemic disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Trophozoites characteristically phagocytose red blood cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: stool antigen test (sensitivity/specificity 100%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: metronidazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Giardia lamblia</i> (see <span>[[Fig. 17-18D|Figure 17-18]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protozoa (flagellate)<br>Most common protozoal cause of diarrhea in United States </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmitted by ingestion of cysts in food and water </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common in day care centers, mental hospitals, hikers, water supplies (chlorination does <i>not</i> kill the cysts), men who have sex with men (anal-oral contact), IgA deficiency, common variable immunodeficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces acute and chronic diarrhea with malabsorption (cysts in formed stool; trophozoites in loose stools)<br>Diagnosis: stool antigen test (sensitivity/specificity 100%)<i>Treatment</i>: tinidazole or nitazoxanide </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces acute and chronic diarrhea with malabsorption (cysts in formed stool; trophozoites in loose stools) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: stool antigen test (sensitivity/specificity 100%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: tinidazole or nitazoxanide </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Helminths</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Anisakis simplex</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intestinal nematode </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmission: eating raw fish dishes (i.e., sushi, sashimi); eating pickled herring </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Larvae penetrate gastric and intestinal mucosa </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produce cramping abdominal pain; epigastric distress with nausea, vomiting, and diarrhea within a few hours after eating </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: endoscopy; IgE antibody test </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: removal by endoscope or surgery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Enterobius vermicularis</i> (see <span>[[Fig. 17-18E|Figure 17-18]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intestinal nematode<br>Most common helminth in the United States </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmission: ingestion of eggs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Eggs deposited in anus by adult worms cause pruritus ani </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Other infections: urethritis in girls; acute appendicitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>No</i> eosinophilia because adult worms are <i>not</i> invasive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: albendazole or mebendazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Trichuris trichiura</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intestinal nematode (whipworm) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmitted by ingestion of eggs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces diarrhea; can produce rectal prolapse in children </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: stool for ova and parasites; eosinophilia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: albendazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Ascaris lumbricoides</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intestinal nematode </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Largest intestinal nematode </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmitted by ingestion of eggs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Larval phase through lungs: cough, pneumonitis, eosinophilia (invasion of tissue) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bowel obstruction in adult phase; no eosinophilia (no invasion of tissue) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: albendazole and mebendazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Necator americanus</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intestinal nematode (hookworm) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adults attach to villi, resulting in blood loss and iron deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: albendazole or mebendazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Strongyloides stercoralis</i> (see <span>[[Fig. 17-18F|Figure 17-18]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intestinal nematode </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmission: filariform larvae in soil penetrate the feet → larval phase through the lungs → swallowed and molt into adults that enter the intestinal mucosa and lay eggs → eggs hatch into rhabditiform larvae which enter the intestinal lumen and are passed in the stool → develop into filariform larvae (infective form) in the soil </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autoinfection may occur if filariform larvae in the intestine penetrate the mucosa and migrate to the lungs to repeat the cycle </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> In immunocompromised patients (e.g., AIDS), massive reinfection occurs with dissemination throughout the body </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces abdominal pain and diarrhea </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ivermectin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Diphyllobothrium latum</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intestinal cestode (tapeworm) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmission: ingest larvae in lake trout (Great Lakes) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produce diarrhea with or without vitamin B<sub>12</sub> deficiency; preferential uptake of vitamin B<sub>12</sub> by the worm </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: eggs in the stool </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: praziquantel </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>ETEC, enterotoxigenic <i>Escherichia coli</i>; STEC, Shiga toxin <i>E. coli</i>; TMP-SMX, trimethoprim-sulfamethoxazole.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>HERNIA</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Direct (see <span>[[Fig. 17-24|Figure 17-24]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Single layer of transversalis is stretched in the floor of the triangle of Hesselbach </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Medial border of triangle is rectus sheath, lateral border is inferior epigastric artery, inferior border is inguinal ligament </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hernia bulges through floor of triangle of Hesselbach; bulge disappears when patient reclines. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small bowel cannot enter scrotal sac; therefore, there is no obstruction or incarceration </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: sutured mesh covering inguinal canal and Hesselbach's triangle </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Indirect (see <span>[[Fig. 17-25|Figure 17-25]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common hernia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pathogenesis in children: persistence of peritoneal connection between inguinal canal and tunica vaginalis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pathogenesis in adults: protrusion of new peritoneal process into inguinal canal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small bowel passes through internal inguinal ring and may enter scrotal sac </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bowel directly hits the examining finger within the inguinal canal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complications: entrapped in inguinal canal (incarceration) or strangulated obstruction (hemorrhagic infarction) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> In children: high ligation of hernia sac at the level of the internal inguinal ring + tightening of the internal inguinal ring </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> In adults: sutured mesh covering inguinal canal and Hesselbach's triangle </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Femoral </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common in women </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bulge located below inguinal ligament </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Highest rate of incarceration of small bowel </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: transversalis fascia and conjoined tendon are sutured to Cooper's ligament </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Umbilical </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common hernia in adults with ascites, pregnancy, or obesity </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common hernia in black newborns </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peritoneal protrusion extends into a fascial defect containing remnants of umbilical cord </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Majority close spontaneously by the second year </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Incarceration more likely in adults than children </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: surgery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ventral </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hernia develops in weakened area of previous surgical excision </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Obesity most common cause </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>FEATURE</b></td><td align="LEFT" valign="BOTTOM"><b>ULCERATIVE COLITIS (UC)</b></td><td align="LEFT" valign="BOTTOM"><b>CROHN'S DISEASE (CD)</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Epidemiology </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> More common in whites than blacks<br>No sex predilection </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> More common in whites than blacks, in Jews than non-Jews </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs between 14 and 38 years of age </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No sex predilection </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lower incidence in smokers and other nicotine users<br>Lower incidence if previous appendectomy <20 years old </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Smoking is a risk factor<br>Majority (>75%) of cases occur between 11 and 35 years of age </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mucosal and submucosal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmural </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Location </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mainly rectum (usually begins in this location)<br>Extends continuously into left colon (may involve entire colon)<br>Does <i>not</i> involve other areas of GI tract </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Terminal ileum alone (30% of cases), ileum and colon (50% of cases), colon alone (20% of cases) (see <span>[[Fig. 17-34|Figure 17-34]]</span>)<br>Involves other areas of GI tract (mouth to anus) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gross features </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inflammatory pseudopolyps (see <span>[[Figs. 17-32|Figure 17-32]]</span> and <span>[[17-33|Figure 17-33]]</span>)<br>Areas of friable, bloody residual mucosa<br>Ulceration and hemorrhage </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thick bowel wall and narrow lumen (leads to obstruction)<br>Aphthous ulcers in bowel (early sign)<br>Skip lesions, strictures, fistulas<br>Deep linear ulcers with cobblestone pattern<br>Fat creeping around serosa </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Microscopic features </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ulcers and crypt abscesses containing neutrophils<br>Dysplasia or cancer may be present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Noncaseating granulomas (60% of cases), lymphoid aggregates (see <span>[[Fig. 17-35|Figure 17-35]]</span>)<br>Dysplasia or cancer less likely </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical findings </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Recurrent left-sided abdominal cramping with bloody diarrhea and mucus<br>Fever, tenesmus, weight loss<br>Extragastrointestinal: primary sclerosing cholangitis (UC > CD), erythema nodosum, iritis/uveitis (CD > UC), pyoderma gangrenosum, HLA-B27 positive arthritis.<br>p-ANCA antibodies > 45% of cases </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Recurrent right lower quadrant colicky pain (obstruction) with diarrhea<br>Bleeding occurs only with colon or anal involvement (fistulas; abscesses)<br>Apthous ulcers in mouth<br>Extragastrointestinal: erythema nodosum, sacroiliitis (HLA-B27 association), pyoderma gangrenosum, iritis (CD > UC), primary sclerosing cholangitis (UC > CD) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Radiography </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> "Lead pipe" appearance in chronic disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> "String" sign in terminal ileum from luminal narrowing by inflammation, fistulas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complications </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Toxic megacolon (hypotonic and distended bowel)<br>Adenocarcinoma: greatest risks are pancolitis, early onset, duration of disease > 10 years) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fistulas, obstruction, colon cancer (UC > CD)<br>Calcium oxalate renal calculi (increased reabsorption of oxalate through inflamed mucosa) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malabsorption due to bile salt deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macrocytic anemia due to vitamin B<sub>12</sub> deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Treatment </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sulfasalazine or mesalamine (5-ASA active metabolite; O<sub>2</sub> free radical scavenger; inhibits lipoxygenase pathway in arachidonic acid metabolism)<br>Corticosteroids for severe disease (systemically or enemas)<br>Nicotine patch<br>Immunosuppressants: azathioprine or cyclosporine<br>Surgery: colectomy with ileostomy usually cures </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sulfasalazine or mesalamine (5-ASA; oral salicylate)<br>Corticosteroids for moderate to severe disease<br>Steroid analogues that target areas of GI tract (e.g., budesonide)<br>Immunosuppressants: azathioprine or cyclosporine<br>Metronidazole for colonic fistulas<br>TNF inhibitors for enterocutaneous fistulas<br>Surgery for obstruction, fistulas, toxic megacolon, refractory disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>ASA, aminosalicylic acid; GI, gastrointestinal; TNF, tumor necrosis factor.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE OF HYPERBILIRUBINEMIA</b></td><td align="LEFT" valign="BOTTOM"><b>URINE BILIRUBIN</b></td><td align="LEFT" valign="BOTTOM"><b>URINE UBG</b></td><td align="LEFT" valign="BOTTOM"><b>EXAMPLES OF DISORDERS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> UCB < 20% </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased production of UCB </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extravascular hemolytic anemias: e.g., spherocytosis, Rh and ABO HDN, warm AIHA </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased uptake or conjugation of UCB </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gilbert's syndrome (familial nonhemolytic jaundice): common AR or AD defect (depends on the type of mutation); occurs in >5% of population); second most common jaundice (hepatitis most common); most common hereditary cause of jaundice; males > females; impaired glucuronyl transferase activity (70-75% decrease in activity); jaundice occurs with fasting or increase in alcohol or phenobarbital intake; serum UCB rarely >5 mg/dL; all other liver function tests are normal; liver biopsy <i>not</i> necessary; no treatment required </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Crigler-Najjar syndromes: genetic disorders with decreased to absent glucuronyl transferase enzyme; type with no enzymes is incompatible with life (liver transplantation necessary) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Physiologic jaundice of newborn: begins on day 3 of life; caused by normal macrophage destruction of fetal RBCs and inability of newborn liver to handle excess load </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Breast milk jaundice: due to pregnane-3α,20α-diol; does <i>not</i> require treatment </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> Mixed </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CB 20-50% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Viral hepatitis: defect in uptake, conjugation of UCB, and secretion of CB </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Obstructive </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CB > 50% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased intrahepatic bile flow </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drug-induced (e.g., OCP) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary biliary cirrhosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dubin-Johnson syndrome: AR disorder in secretion into intrahepatic bile ducts; black pigment in hepatocytes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rotor's syndrome: AR disorder similar to Dubin-Johnson syndrome but without black pigment in hepatocytes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased extrahepatic bile flow </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gallstone in common bile duct </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Carcinoma of head of pancreas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> </td></tr></tbody></table><a name=""></a> <br>AD, autosomal dominant; AIHA, autoimmune hemolytic anemia; AR, autosomal recessive; CB, conjugated bilirubin; HDN, hemolytic disease of newborn; OCP, oral contraceptive pill; UBG, urobilinogen; UCB, unconjugated bilirubin.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TEST</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Liver Cell Necrosis</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum alanine transaminase (ALT) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Specific enzyme for liver cell necrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present in the cytosol </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ALT > AST: viral hepatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum aspartate transaminase (AST) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present in mitochondria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alcohol damages mitochondria: AST > ALT indicates alcoholic hepatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Cholestasis</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum γ-glutamyltransferase (GGT) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intra- or extrahepatic obstruction to bile flow </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Induction of cytochrome P-450 system (e.g., alcohol): increases GGT </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum alkaline phosphatase (ALP) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal GGT and increased ALP: source of ALP other than liver (e.g., osteoblastic activity in bone) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased GGT and ALP: liver cholestasis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Bilirubin Excretion</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CB < 20% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Unconjugated hyperbilirubinemia: e.g., extravascular hemolytic anemias </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CB 20-50% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mixed hyperbilirubinemia (e.g., viral hepatitis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CB > 50% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Conjugated hyperbilirubinemia (e.g., liver cholestasis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urine bilirubin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bilirubinuria: viral hepatitis, intra- or extrahepatic obstruction of bile ducts </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urine UBG </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased urine UBG: extravascular hemolytic anemias, viral hepatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent urine UBG: liver cholestasis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Hepatocyte Function</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum albumin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Albumin is synthesized by the liver </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypoalbuminemia: severe liver disease (e.g., cirrhosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prothrombin time (PT) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Majority of coagulation factors are synthesized in the liver </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased PT: severe liver disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Blood urea nitrogen (BUN) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urea cycle is present in the liver </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased serum BUN: cirrhosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum ammonia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ammonia is metabolized in the urea cycle in the liver </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Derives from large bowel and amino acid degradation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased serum ammonia: cirrhosis, Reye syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Immune Function</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum IgM </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased in primary biliary cirrhosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antimitochondrial antibody </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary biliary cirrhosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-smooth muscle antibody </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autoimmune hepatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antinuclear antibody (ANA) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autoimmune hepatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Tumor Marker</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> α-Fetoprotein (AFP) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatocellular carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>CB, conjugated bilirubin; UBG, urobilinogen.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>% CB</b></td><td align="LEFT" valign="BOTTOM"><b>AST</b></td><td align="LEFT" valign="BOTTOM"><b>ALT</b></td><td align="LEFT" valign="BOTTOM"><b>ALP</b></td><td align="LEFT" valign="BOTTOM"><b>GGT</b></td><td align="LEFT" valign="BOTTOM"><b>UB</b></td><td align="LEFT" valign="BOTTOM"><b>URINE UBG</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Viral hepatitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 20-50% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑↑↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alcoholic hepatitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 20-50% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cholestasis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >50% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extravascular hemolysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <20% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑<br>RBCs </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="8"> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="8"> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="8"> </td></tr></tbody></table><a name=""></a> <br><i>Arrows</i> represent degree of magnitude.<br>ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CB, conjugated bilirubin; GGT, γ-glutamyltransferase; UB, urine bilirubin; UBG, urobilinogen.<br>From Goljan EF, Sloka KI: Rapid Review Laboratory Testing in Clinical Medicine. St. Louis, Mosby, 2008, Table 9-20, p 312.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>VIRUS</b></td><td align="LEFT" valign="BOTTOM"><b>TRANSMISSION</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatitis A (HAV) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fecal-oral </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infectious hepatitis<br>Incubation 15-50 days (average 30 days) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Accounts for 37% of acute hepatitis in U.S. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most preventable infection in travelers </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased incidence in children/employees in day care centers, prisons, travelers to developing countries, males who have sex with males (anal intercourse), parents adopting children from other countries </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical: jaundice > 70%; fever; nausea/vomiting; abdominal pain </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Majority recover; no carrier state; no chronic hepatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serology: see text </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Passive immunization: immunoglobulin (passive transfer of antibodies) for pre-exposure prophylaxis and postexposure prophylaxis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Active immunization: protective antibodies in 1 month </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatitis B (HBV) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Parenteral, orally, sexual, vertical (pregnancy, breast feeding) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Incubation 30-180 days<br>Primarily spread via blood (IVDA) and sexually<br>Accounts for 45% of acute hepatitis in U.S.<br>Clinical: variable fever; profound malaise; painful hepatomegaly (87%); serum sickness prodrome (15-20%): immunocomplex disease (HBsAg + antibody); vasculitis (PAN), urticaria, polyarthritis, membranous glomerulopathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Recovery in >90% of immunocompetent patients; 1-2% develop chronic hepatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Newborns and immunodeficient patients more likely to develop chronic hepatitis (>90%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complications: fulminant hepatitis <1% especially if coinfected with hepatitis D; hepatocellular carcinoma secondary to postnecrotic cirrhosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serology: see text </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prevention: immunization with recombinant vaccine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i> of chronic hepatitis: pegylated IFN-α; nucleoside analogues that block viral replication (e.g., lamivudine; entecavir); liver transplant </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatitis C (HCV) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Parenteral, sexual </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Incubation 2-26 weeks (average, 6-7 weeks) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common blood-borne infection in the U.S. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Accounts for 18% of acute hepatitis in U.S. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common main indication for liver transplantation in U.S. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most cases due to IVDA (60%); hemophiliacs transfused before 1987 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Post-transfusion hepatitis rare due to screening </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Maternal-fetal transmission is infrequent (estimated 5%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical: mild hepatitis (70-80% subclinical); jaundice uncommon (80% anicteric) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic hepatitis in >70% of cases </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Other clinical associations: type I MPGN, alcohol excess, PCT, lichen planus, B cell lymphoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complications: hepatocellular carcinoma secondary to postnecrotic cirrhosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prevention: no preventive vaccine available </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: early treatment of acute infection with pegylated IFN-α may prevent chronic infection; pegylated IFN-α also used in treating chronic HCV; liver transplant </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatitis D (HDV) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Parenteral, sexual </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Incomplete RNA virus that requires HBsAg to replicate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Accounts for <1% of acute hepatitis in U.S. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic state less likely with coinfection (HBV and HDV exposure at same time) than superinfection (HBV carrier exposed to blood containing HBV and HDV) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic infection develops in 60-85% of people infected </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serology: see text </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prevention: immunization with recombinant vaccine for HBV </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatitis E </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fecal-oral (water-borne) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs in developing countries<br>Only produces acute hepatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fulminant hepatitis may develop in pregnant women </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>HBsAg, surface antigen; IFN, interferon; IVDA, intravenous drug abuse; MPGN, membranoproliferative glomerulonephritis; PAN, polyarteritis nodosa; PCT, porphyria cutanea tarda.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>HBsAg</b></td><td align="LEFT" valign="BOTTOM"><b>HBeAg HBV DNA</b></td><td align="LEFT" valign="BOTTOM"><b>Anti-HBc-IgM</b></td><td align="LEFT" valign="BOTTOM"><b>Anti-HBc-IgG</b></td><td align="LEFT" valign="BOTTOM"><b>Anti-HBs</b></td><td align="LEFT" valign="BOTTOM"><b>INTERPRETATION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Earliest phase of acute HBV </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute infection </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Window phase, or serologic gap </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Recovered from HBV </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Immunized </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> "Healthy" carrier </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> + </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> - </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infective carrier </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="6"> </td></tr></tbody></table><a name=""></a> <br>Anti-HBc, core antibody; anti-HBs, surface antibody; HBeAg, e antigen; HBsAg, surface antigen.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>PATHOGEN(S)</b></td><td align="LEFT" valign="BOTTOM"><b>CHARACTERISTICS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ascending cholangitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Escherichia coli</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inflammation of bile ducts (cholangitis) from concurrent biliary infection and duct obstruction (e.g., stone) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Life-threatening disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Triad of fever, jaundice, RUQ pain </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of multiple liver abscesses </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: decompression and drainage; piperacillin-tazobactam </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Liver abscess </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Escherichia coli</i>, <i>Bacteroides fragilis</i>, <i>Streptococcus faecalis</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Majority are in the right lobe; majority are solitary<br>Causes: ascending cholangitis (most common); intra-abdominal infection (e.g., spread via the portal vein, diverticulitis, bowel perforation); direct extension (e.g., empyema of gallbladder, subphrenic abscess); hematogenous spread (e.g., bacterial endocarditis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical: spiking, intermittent fever; RUQ or right costovertebral angle tenderness; jaundice is uncommon </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: ultrasound (least expensive); CT scan </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: percutaneous drainage; metronidazole + ceftriaxone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Granulomatous hepatitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Mycobacterium tuberculosis</i>, <i>Histoplasma capsulatum</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sign of miliary spread (refer to <span macro="tag [[16 Upper and Lower Respiratory Disorders]] [[Chapter 16]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Spontaneous peritonitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Escherichia coli</i> in adults, <i>Streptococcus pneumoniae</i> in children </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Develops in ascites (e.g., cirrhosis, nephrotic syndrome)<br><i>Treatment</i>: cefotaxime </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Leptospirosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Leptospira interrogans</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative; tightly wound spirochetes; crook at the end resembles a shepherd's staff </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Reservoirs: rats, dogs (most common); spirochetes excreted in urine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmission: swimming in contaminated water (ponds on farms); farmers, miners, people who work with sewage </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Biphasic disease (Weil's disease): </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Septicemic phase: fever, jaundice, hemorrhagic diathesis, renal failure (interstitial nephritis), conjunctivitis and photophobia, meningitis; phase terminated by the appearance of antibodies (beginning of immune phase) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Immune phase: presence of numerous organisms in the urine; urine best examined by darkfield microscopy to confirm the diagnosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: penicillin G </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Amebiasis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Entamoeba histolytica</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protozoan (ameba) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of a liver abscess worldwide (<i>not</i> in the United States) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Usually produces a right lobe abscess (refer to <span macro="tag [[17 Gastrointestinal Disorders]] [[Chapter 17]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: metronidazole followed by paromomycin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clonorchiasis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Clonorchis sinensis</i> (Chinese liver fluke) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intestinal fluke (trematode) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nonschistosomal life cycle: egg (human) → ciliated miracidial larva → infects snail (1st intermediate host) → produce fork-tailed cercarial larvae → infect a 2nd intermediate host (fish in clonorchiasis) → form infective metacercariae → man ingests the 2nd intermediate host → develops disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted by ingesting encysted larvae in fish; larvae enter CBD and become adults. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May produce cholangiocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: praziquantel </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Schistosomiasis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Schistosoma mansoni</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fluke (trematode) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Schistosomal life cycle: egg (human) → ciliated miracidial larva → infects snail (1st intermediate host) → produce fork-tailed cercarial larvae → penetrate skin in human → produce disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Schistosoma mansoni</i>: larvae in the superior mesenteric vein enter into the portal vein, where they develop into adult worms that deposit eggs to which the host develops an inflammatory response marked by concentric fibrosis ("pipestem cirrhosis") in the vessel wall </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complications of cirrhosis: portal hypertension, ascites, esophageal varices </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: praziquantel </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Echinococcosis (see <span>[[Fig. 18-4|Figure 18-4]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Echinococcus granulosus</i> (sheepherder's disease) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intestinal tapeworm (cestode)<br>Single or multiple cysts containing larval forms; cysts can be in the liver (most common site), lungs, and brain </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Eggs develop into a larval form only; larval form only develops into an adult, which can lay eggs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infected sheep is intermediate host (larval form in liver cyst); dog that eats the sheep liver is the definitive host (larva develops into adults, which produce eggs); human who eats the eggs from the dog becomes the intermediate host (eggs develop into larvae, which penetrate the bowel and enter the liver to produce the hydatid cyst) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Can be contracted by children eating grass contaminated with dog excreta </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inner germinal layer of hydatid cysts has protoscolices (larva) in brood capsules </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rupture of cysts can produce anaphylaxis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: percutaneous drainage + albendazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>CBD, common bile duct; RUQ, right upper quadrant.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>CAUSE</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Tumors</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Angiosarcoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vinyl chloride, arsenic, thorium dioxide (radioactive contrast material) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cholangiocarcinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thorium dioxide </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatocellular carcinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vinyl chloride, aflatoxin (due to <i>Aspergillus</i> mold) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Liver cell adenoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oral contraceptive pills </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Other Liver Diseases</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute hepatitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Isoniazid (caused by toxic metabolite), halothane, acetaminophen, methyldopa </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cholestasis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oral contraceptive pills (OCPs; estrogen interferes with intrahepatic bile secretion), anabolic steroids (same mechanism as OCPs) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fatty change </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Amiodarone (resembles alcoholic hepatitis; Mallory bodies and progression to cirrhosis), methotrexate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fibrosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Methotrexate, retinoic acid, amiodarone </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE</b></td><td align="LEFT" valign="BOTTOM"><b>DEFINITION</b></td><td align="LEFT" valign="BOTTOM"><b>CAUSES</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Functional </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protein < 2 g/24 hr </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fever, exercise, congestive heart failure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Not</i> associated with renal disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Orthostatic (postural): occurs with standing and is absent in the recumbent state; urine protein is absent in the first morning void; <i>no</i> progression to renal disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Overflow </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protein loss is variable </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Multiple myeloma with BJ proteinuria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> LMW proteinuria </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemoglobinuria: e.g., intravascular hemolysis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Amount filtered > tubular reabsorption </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Myoglobinuria: crush injuries, McArdle's glycogenosis (deficient muscle phosphorylase); increase in serum creatine kinase </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glomerular </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nephritic syndrome: protein > 150 mg/24 hr, but <3.5 g/24 hr<br>Nephrotic syndrome: protein > 3.5 g/24 hr </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Damage of GBM: nonselective proteinuria with loss of albumin and globulins; example is post-streptococcal glomerulonephritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of negative charge on GBM: selective proteinuria with loss of albumin and <i>not</i> globulins; example is minimal change disease (lipoid nephrosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tubular </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protein < 2 g/24 hr<br>Defect in proximal tubule reabsorption of LMW proteins (e.g., amino acids at normal filtered loads </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Heavy metal poisoning: e.g., lead and mercury poisoning<br>Fanconi syndrome: inability to reabsorb glucose, amino acids, uric acid, phosphate, and bicarbonate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hartnup disease: defect in reabsorption of neutral amino acids (e.g., tryptophan) in the gastrointestinal tract and kidneys </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>BJ, Bence Jones protein; GBM, glomerular basement membrane; LMW, low molecular weight.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CAUSE</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Increased Serum BUN</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased cardiac output </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CHF, shock (e.g., hemorrhage)<br>↓ Cardiac output → ↓ GFR → ↑ proximal tubule reabsorption of urea → ↑ serum BUN </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased protein intake </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> High-protein diet, blood in gastrointestinal tract </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ Amino acid degradation → ↑ serum BUN </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased tissue catabolism </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Third-degree burns, postoperative state </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ Amino acid degradation → ↑ serum BUN </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute glomerulonephritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Poststreptococcal glomerulonephritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ GFR → ↑ serum BUN </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute or chronic renal failure </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute tubular necrosis, diabetic glomerulopathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ GFR → ↑ serum BUN </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Postrenal disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urinary tract obstruction (e.g., urinary stone, BPH) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ GFR back-diffusion of urea →↑ serum BUN </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Decreased Serum BUN</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased plasma volume </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal pregnancy, SIADH </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ Plasma volume → ↑ GFR → ↓ serum BUN </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased urea synthesis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cirrhosis, Reye syndrome, fulminant liver failure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dysfunctional urea cycle → ↓ serum BUN </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased protein intake </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Kwashiorkor (↑ CHO is protein sparer), starvation gluconeogenesis in kidneys </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ Amino acid degradation → ↓ serum BUN </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>BPH, benign prostatic hyperplasia; BUN, blood urea nitrogen; CHF, congestive heart failure; CHO, carbohydrate; GFR, glomerular filtration rate; SIADH, syndrome of inappropriate antidiuretic hormone.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CAUSE</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Increased CCr</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal pregnancy </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal increase in plasma volume causes an increase in the GFR leading to an increase in CCr; highest at the end of the first trimester </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Early diabetic glomerulopathy </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Efferent arteriole becomes constricted due to hyaline arterioloclerosis causing an increase in the GFR and CCr </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased GFR damages the glomerulus (hyperfiltration injury) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Decreased CCr</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Elderly people </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> GFR normally decreases with age causing a corresponding decrease in the CCr; danger when using nephrotoxic drugs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute and chronic renal disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ARF due to acute tubular necrosis, CRF due to diabetic glomerulopathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>ARF, acute renal failure; CRF, chronic renal failure; GFR, glomerular filtration rate.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>COMPONENTS</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>General Examination</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Color </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dark yellow: concentrated urine, bilirubinuria, ↑ UBG, vitamins </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Red or pink: hematuria, hemoglobinuria, myoglobinuria, drugs (e.g., phenazopyridine, a urinary anesthetic), porphyria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Smoky-colored urine: acid pH urine converts Hb to hematin; common finding in nephritic type of glomerulonephritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Black urine after exposure to light: alkaptonuria (AR disease with deficiency of homogentisate oxidase) with an increase in homogentisic acid in the urine; turns black when exposed to light </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clarity </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cloudy urine with alkaline pH: normal finding most often due to phosphates </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cloudy urine with acid pH: normal finding most often due to uric acid </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Other: bacteria, WBCs, Hb, myoglobin also decrease clarity </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Specific gravity </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Evaluates urine concentration and dilution </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Specific gravity > 1.023 (UOsm 900 mOsm/kg) indicates urine concentration and <i>excludes</i> intrinsic renal disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypotonic urine has a specific gravity <1.015 (∼ UOsm 220 mOsm/kg) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> UOsm is the best indicator of urine concentration/dilution </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fixed specific gravity (1.008-1.010): correlates with UOsm; lack of concentration and dilution (e.g., chronic renal failure) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Chemical Dipsticks</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> pH </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Determined by diet and acid-base status of the patient; pure vegan usually has alkaline pH (citrate converted into bicarbonate); meat eater usually has acid pH (organic acids in meat) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alkaline pH + smell of ammonia: urease-producing pathogen (e.g., <i>Proteus</i>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protein </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Detects albumin (<i>not</i> globulins) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> SSA: detects albumin and globulins (e.g., BJ protein) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Albuminuria: reagent strip and SSA have the <i>same</i> results </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> BJ protein: SSA <i>greater than</i> reagent strip result; always confirm BJ protein with urine immunoelectrophoresis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glucose </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Specific for glucose; will not detect fructose or other sugars </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Detect glucose in urine as low as 30 mg/dL </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ Serum glucose + glucosuria: diabetes mellitus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal serum glucose + glucosuria: normal pregnancy (normally have a low renal threshold for glucose), benign glucosuria (low renal threshold for glucose) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Microalbuminuria dipsticks: more sensitive than standard dipstick; sensitive to 1.5-8 mg/dL; microalbuminuria is the first sign of diabetic nephropathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ketones </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Detects acetone, acetoacetic acid (<i>not</i> β-OHB); nitroprusside in the test system only reacts with AcAc and acetone, <i>not</i> β-OHB. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ketonuria: DKA, starvation, ketogenic diets, pregnancy (normal finding), isopropyl alcohol poisoning </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bilirubin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Detects conjugated (water-soluble) bilirubin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bilirubinuria: viral hepatitis, obstructive jaundice </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urobilinogen </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal to have trace amounts (normal urine color is due to urobilin) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent urine UBG, ↑ urine bilirubin: obstructive jaundice </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ Urine UBG, absent urine bilirubin: extravascular hemolytic anemia (e.g., hereditary spherocytosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ Urine UBG, ↑ urine bilirubin: hepatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Blood </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Detects RBCs, Hb, and myoglobin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hematuria: e.g., renal stone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemoglobinuria: e.g., intravascular hemolytic anemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Myoglobinuria: e.g., crush injuries; ↑ serum creatine kinase </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nitrites </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Detects nitrites produced by nitrate reducing uropathogens (e.g., <i>E. coli</i>); test sensitivity and specificity is 30% and 90%, respectively; requires ∼ 4 hr for nitrate reducing uropathogens to convert nitrates to nitrites and patients with UTI frequently have increased frequency of urination, which explains the tests poor sensitivity </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Leukocyte esterase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Detects esterase in neutrophils (pyuria); ∼ 80% sensitivity<br>Infections: urethritis, cystitis, pyelonephritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sterile pyuria (neutrophils present but <i>negative standard urine culture</i>): <i>Chlamydia trachomatis</i> urethritis, tuberculosis, drug-induced interstitial nephritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Sediment</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bacteria: usually a sign of a urinary tract infection </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Red blood cells (hematuria): renal stone, cancer (bladder, renal), glomerulonephritis; hematuria is >2-3 RBCs per HPF </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dysmorphic RBCs: indicates hematuria of glomerular origin (see <span>[[Fig. 19-2A|Figure 19-2]]</span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neutrophils (pyuria; see <span>[[Fig. 19-2B|Figure 19-2]]</span>): urinary tract infection, sterile pyuria; pyuria refers to ≥10 WBCs/HPF in a centrifuged specimen or ≥5 WBCs/HPF in an uncentrifuged specimen </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oval fat bodies (see <span>[[Fig. 19-2C|Figure 19-2]]</span>): renal tubular cells with lipid (nephrotic syndrome) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Casts </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Casts are formed in tubular lumens in the kidney; they are composed of a protein matrix (Tamm-Horsfall protein) within which are entrapped cells, debris, or protein leaking through the glomeruli; their presence proves a renal origin of the disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hyaline cast (see <span>[[Fig. 19-2D|Figure 19-2]]</span>): acellular, ghost-like cast containing protein; no significance in the absence of proteinuria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> RBC cast (see <span>[[Fig. 19-2E|Figure 19-2]]</span>): nephritic type of glomerulonephritis (e.g., post-streptococcal glomerulonephritis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> WBC cast (see <span>[[Fig. 19-2F|Figure 19-2]]</span>): acute pyelonephritis, acute tubulointerstitial nephritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal tubular cell cast (see <span>[[Fig. 19-2G|Figure 19-2]]</span>): acute tubular necrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fatty cast: contains lipid (e.g., cholesterol); sign of nephrotic syndrome (e.g., lipoid nephrosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Waxy (broad) cast (see <span>[[Fig. 19-2H|Figure 19-2]]</span>): refractile, acellular cast; sign of chronic renal failure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Crystals </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Calcium oxalate: pure vegan diet, ethylene glycol poisoning, calcium oxalate stone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Uric acid: hyperuricemia associated with gout or massive destruction of cells after chemotherapy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Triple phosphate: may be a sign of urinary tract infection due to urease producing uropathogens (e.g., <i>Proteus</i> species) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cystine: hexagonal crystal seen in cystinuria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>AcAc, acetoacetic acid; AR, autosomal recessive; BJ, Bence Jones; DKA, diabetic ketoacidosis; Hb, hemoglobin; HPF, high-powered field; β-OHB, hydroxybutyric acid; SSA, sulfosalicylic acid; UBG, urobilinogen; UTI, urinary tract infection.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CYSTIC DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal dysplasia (see <span>[[Fig. 19-5|Figure 19-5]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cystic disease in children </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No inheritance pattern </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Abnormal development of one or both kidneys; abnormal structures persist in the kidneys (e.g., cartilage, immature collecting ductules). </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present as an enlarged, irregular, cystic, unilateral (bilateral) flank mass </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bilateral dysplastic kidneys may lead to renal failure; accounts for ∼ 20% of cases of CRF in children </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Juvenile polycystic kidney disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> AR inheritance </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bilateral cystic disease; cysts in the cortex and medulla </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cysts also occur in the liver </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Association with congenital hepatic fibrosis leading to portal hypertension </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Enlarged kidneys at birth; most serious types are incompatible with life </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Maternal oligohydramnios (decreased amniotic fluid); newborns have Potter's facies, a deformation due to oligohydramnios; findings include low-set ears, parrot beak nose, and lung hypoplasia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adult polycystic kidney disease (see <span>[[Fig. 19-6|Figure 19-6]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> AD inheritance; defect on chromosome 16<br>Bilateral cystic disease develops by 20-25 years of age; bilaterally palpable kidneys; cysts involve all parts of the nephron in the cortex and medulla </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cysts are present in the liver (50%), pancreas (10%), spleen (5%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypertension (>80% of cases); associated with stroke due to rupture of intracranial berry aneurysms (aneurysms in 10-30% of cases), intracerebral hemorrhage, lacunar infarcts </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CRF begins at age 40-60; due to destruction of kidneys by slowly expanding cysts; accounts for ∼ 10% of cases of CRF; it is the most common cause of death </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Other associations: sigmoid diverticulosis, hematuria, mitral valve prolapse, slight risk for developing renal cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Treatment: renal transplantation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Medullary sponge kidney </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No inheritance pattern<br>Most commonly discovered with an IVP; striations are present in the papillary ducts of the medulla ("Swiss-cheese" appearance); multiple cysts of the collecting ducts are present in the medulla </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Recurrent UTIs, hematuria, and renal stones </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acquired polycystic kidney disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause is renal dialysis; occurs in ∼ 50% of patients on long-term dialysis<br>Tubules are obstructed by interstitial fibrosis or oxalate crystals </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small risk for developing renal cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Simple retention cysts </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common adult renal cyst<br>Derived from tubular obstruction </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May produce hematuria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Requires needle aspiration to distinguish it from renal cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>AD, autosomal dominant; AR, autosomal recessive; CRF, chronic renal failure; IVP, intravenous pyelogram; UTIs, urinary tract infections.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TERM</b></td><td align="LEFT" valign="BOTTOM"><b>DESCRIPTION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Focal glomerulonephritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Only a few glomeruli are abnormal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diffuse glomerulonephritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> All glomeruli are abnormal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Proliferative glomerulonephritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >100 nuclei in affected glomeruli </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Membranous glomerulopathy </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thick GBM, no proliferative change </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Membranoproliferative glomerulonephritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thick GBM, hypercellular glomeruli </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Focal segmental glomerulosclerosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fibrosis involving only a segment of the involved glomerulus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Crescentic glomerulonephritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Proliferation of parietal epithelial cells around glomerulus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary glomerular disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Involves only glomeruli and no other target organs (e.g., minimal change disease) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secondary glomerular disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Involves glomeruli and other target organs (e.g., SLE) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>GBM, glomerular basement membrane; SLE, systemic lupus erythematosus.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>GLOMERULAR DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>CLINICOPATHOLOGIC FINDINGS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IgA glomerulopathy (Berger's disease) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common nephropathy; majority are nephritic (5% nephrotic)<br>Affects children and adults </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased mucosal synthesis and decreased clearance of IgA; increased serum IgA (50%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Focal proliferative glomerulopathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mesangial IgA IC deposits with granular IF; ICs activate alternative complement pathway </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Overlapping features with HSP may occur </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Episodic bouts of hematuria (microscopic or gross) usually following an upper respiratory infection; hypertension </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Slow progression to CRF (40-50%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroids decrease proteinuria; treat hypertension </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Post-streptococcal glomerulonephritis (see <span>[[Fig. 19-7C, F, and G|Figure 19-7]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common type of postinfectious GN<br>Usually follows group A streptococcal infection of skin (e.g., scarlet fever) or pharynx<br>Subepithelial IC deposits with granular IF; ICs activate alternative complement pathway </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diffuse proliferative pattern with neutrophil infiltration </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hematuria 1-3 weeks following group A streptococcal infection by a nephritogenic strain (never produces acute rheumatic fever); periorbital edema (sodium retention); edema can occasionally be more extensive but is related to sodium retention <i>no</i>t hypoalbuminemia; hypertension (usually transient; sometimes severe) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased anti-DNase B titers; ASO is degraded by oil in the skin and is <i>not</i> increased; streptozyme test is positive (can detect anti-DNase B, ASO, anti-AH, and anti-NAD antibodies) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Usually resolves; CRF is uncommon </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: supportive; penicillin G or V if cultures are positive for <i>Streptococcus pyogenes</i>; treat hypertension </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diffuse proliferative glomerulonephritis (SLE) (see <span>[[Fig. 19-7C and E|Figure 19-7]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diffuse proliferative GN is most common subtype of glomerular disease in SLE; other types can have a nephrotic presentation<br>Subendothelial IC deposits with granular IF; DNA-anti-DNA ICs activate classical complement pathway </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> "Wire looping" of capillaries (corresponds with subendothelial ICs); neutrophil infiltration with hyaline thrombi in capillary lumens </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Kidneys are major target organ in SLE (∼ 90%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum ANA test usually has a rim pattern, which corresponds with the presence of anti-dsDNA antibodies </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Evolves into CRF in most cases; common cause of death in SLE </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroids + cyclophosphamide </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rapidly progressive crescentic glomerulonephritis (see <span>[[Fig. 19-7B and H|Figure 19-7]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical syndrome that may be primary or secondary type of glomerular disease<br>Rapid loss of renal function progresses to ARF over days to weeks; very poor prognosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May or may not be associated with crescent formation (crescentic GN) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical associations: Goodpasture's syndrome, microscopic polyarteritis (p-ANCA), Wegener's granulomatosis (c-ANCA) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Goodpasture syndrome: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Male dominant disease; 80% HLA-BR2 positive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-basement membrane antibodies against collagen in glomerular and pulmonary capillaries </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Linear IF; EM has <i>no</i> electron-dense deposits; crescentic GN (accounts for 5% of all cases) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Begins with hemoptysis and ends with renal failure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: plasma exchange; immunosuppressive therapy with corticosteroids and cyclophosphamide; renal transplantation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>AH, antihyaluronidase; ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic antibody; ARF, acute renal failure; ASO, antistreptolysin O; CRF, chronic renal failure; ds, double-stranded; EM, electron microscopy; GN, glomerulonephritis; HSP, Henoch-Schönlein purpura; IC, immunocomplex; IF, immunofluorescence; NAD, nicotinamide adenine dinucleotidase; SLE, systemic lupus erythematosus.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>GLOMERULAR DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>CLINICOPATHOLOGIC FINDINGS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Minimal change disease (lipoid nephrosis) (see <span>[[Fig. 19-7D|Figure 19-7]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of nephrotic syndrome in children; more common in girls than boys; occurs in ∼ 15% of adults with nephrotic syndrome<br>T-cell cytokines cause the GBM to lose its negative charge; selective proteinuria (albumin <i>not</i> globulins) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secondary causes: Hodgkin's lymphoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Structurally normal glomeruli; positive fat stains in glomerulus and tubules </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Negative IF; EM shows fusion of podocytes and <i>no</i> deposits </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Often preceded by respiratory infection or routine immunization </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Usually normotensive (90%), unlike other types of nephrotic syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: children respond well to steroid therapy; CRF is rare </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Focal segmental glomerulosclerosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary or secondary disease; secondary causes-HIV (most common glomerular disease) and intravenous heroin abuse </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Negative IF; EM focal damage of VECs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nonselective proteinuria, microscopic hematuria (60-80%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypertension early (20%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Poor prognosis; commonly progresses to CRF </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroids (only 15-20% response) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diffuse membranous glomerulopathy (see <span>[[Fig. 19-7I|Figure 19-7]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of nephrotic syndrome in adults<br>Primary and secondary types; secondary causes: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drugs: e.g., captopril, gold therapy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infections: HBV, <i>Plasmodium malariae</i>, syphilis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignancy: carcinomas, Hodgkin's lymphoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autoimmune disease: SLE (nephrotic presentation) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diffuse thickening of membranes; silver stains show "spike and dome" pattern beneath VECs (subepithelial deposits) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Subepithelial ICs with granular IF </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroids may slow progression </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type I MPGN </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common type of MPGN; nephrotic presentation (60%); some cases have a nephritic presentation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with HBV, HCV (more common), or cryoglobulinemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Subendothelial ICs with granular IF; ICs activate classical and alternative complement pathways; EM shows tram tracks caused by splitting of the GBM by an ingrowth of mesangium </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypertension (35%); majority have hematuria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Majority progress to CRF </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: response to corticosteroids <i>not</i> established </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type II MPGN </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with the C3 nephritic factor (C3NeF), an autoantibody that binds to C3 convertase (C3bBb); prevents degradation of C3 convertase causing sustained activation of C3 resulting in very low C3 levels </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diffuse intramembranous deposits ("dense deposit disease"); EM shows tram tracks </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypertension (35%); majority have hematuria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Majority progress to CRF </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: response to corticosteroids <i>not</i> established </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>CRF, chronic renal failure; EM, electron microscopy; GBM, glomerular basement membrane; HBV, hepatitis B; HCV, hepatitis C; ICs, immunocomplexes; IF, immunofluorescence; MPGN, membranoproliferative glomerulonephritis; SLE, systemic lupus erythematosus; VECs, visceral epithelial cells.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>MEDIATOR</b></td><td align="LEFT" valign="BOTTOM"><b>SOURCE(S)</b></td><td align="LEFT" valign="BOTTOM"><b>FUNCTION(S)</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> Arachidonic acid metabolites </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prostaglandins </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macrophages, endothelial cells, platelets<br>PGH<sub>2</sub>: major precursor of PGs and thromboxanes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> PGE<sub>2</sub>: vasodilation, pain, fever<br>PGI<sub>2</sub>: vasodilation; inhibition of platelet aggregation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thromboxane A<sub>2</sub> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelets<br>Converted from PGH<sub>2</sub> by thromboxane synthase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vasoconstriction, platelet aggregation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Leukotrienes (LTs) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Leukocytes<br>Converted from arachidonic acid by lipoxygenase-mediated hydroxylation </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> LTB<sub>4</sub>: chemotaxis and activation of neutrophil adhesion molecules<br>LTC<sub>4</sub>, LTD<sub>4</sub>, LTE<sub>4</sub>: vasoconstriction, increased venular permeability, bronchoconstriction </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Zileuton inhibits 5-lipoxygenase: ↓ synthesis LTB<sub>4</sub>, LTC<sub>4</sub>, LTD<sub>4</sub>, LTE<sub>4</sub> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Montelukast leukotriene receptor antagonist: ↓ synthesis LTC<sub>4</sub>, LTD<sub>4</sub>, LTE<sub>4</sub> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bradykinin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Product of kinin system activation by activated factor XII </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vasodilation, increased venular permeability, pain </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chemokines </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Leukocytes, endothelial cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Activate neutrophil chemotaxis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complement </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Synthesized in liver (acute phase reactant) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> C3a, C5a (anaphylatoxins): stimulate mast cell release of histamine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> C3b: opsonization </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> C5a: activation of neutrophil adhesion molecules, chemotaxis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> C5-C9 (membrane attack complex): cell lysis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> Cytokines </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IL-1, TNF </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macrophages (main source), monocytes, dendritic cells, endothelial cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Initiate PGE<sub>2</sub> synthesis in anterior hypothalamus, leading to production of fever<br>Activate endothelial cell adhesion molecules </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increase liver synthesis of acute-phase reactants, such as ferritin, coagulation factors (e.g., fibrinogen), and C-reactive protein </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increase release of neutrophils from bone marrow (neutrophil leukocytosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> TNF is a promoter of apoptosis (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IL-6 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increase liver synthesis of acute phase reactants </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IL-8 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chemotaxis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Histamine </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mast cells (primary cell), platelets, enterochromaffin cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vasodilation, increased venular permeability </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nitric oxide (NO) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macrophages, endothelial cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vasodilation, bactericidal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Free radical gas released during conversion of arginine to citrulline by NO synthase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serotonin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelets </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vasodilation, increased venular permeability, increases collagen synthesis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>IL, interleukin; PG, prostaglandin; TNF, tumor necrosis factor.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>FEATURE</b></td><td align="LEFT" valign="BOTTOM"><b>ACUTE INFLAMMATION</b></td><td align="LEFT" valign="BOTTOM"><b>CHRONIC INFLAMMATION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pathogenesis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Microbial pathogens, trauma, burns </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Persistent acute inflammation, foreign bodies (e.g., silicone, glass), autoimmune disease, certain types of infection (e.g., tuberculosis, leprosy) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary cells involved </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neutrophils </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Monocytes/macrophages (key cells), B and T lymphocytes, plasma cells, fibroblasts </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary mediators </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Histamine (key mediator), prostaglandins, leukotrienes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cytokines (e.g., IL-1), growth factors </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Necrosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Less prominent </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Scar tissue </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Onset </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Immediate </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Delayed </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Duration </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Few days </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Weeks, months, years </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Outcome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complete resolution, progression to chronic inflammation, abscess formation </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Scar tissue formation, disability, amyloidosis (refer to <span macro="tag [[03 Immunopathology]] [[Chapter 3]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Main immunoglobulin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IgM </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IgG </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum protein electrophoresis effect </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mild hypoalbuminemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Polyclonal gammopathy; greater degree of hypoalbuminemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral blood leukocyte response </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neutrophilic leukocytosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Monocytosis </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>FACTOR</b></td><td align="LEFT" valign="BOTTOM"><b>FUNCTION(S)</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Growth Factors</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vascular endothelial cell growth factor (VEGF) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stimulates angiogenesis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Basic fibroblast growth factor (BFGF) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stimulates angiogenesis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Epidermal growth factor (EGF) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stimulates keratinocyte migration </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stimulates granulation tissue formation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelet-derived growth factor (PDGF) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stimulates proliferation of smooth muscle, fibroblasts, endothelial cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transforming growth factor-β (TGF-β) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chemotactic for macrophages, lymphocytes, fibroblasts </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Hormones</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insulin growth factor-1 (IGF-1) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stimulates synthesis of collagen </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Promotes keratinocyte migration </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Interleukins (IL)</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IL-1 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chemotactic for neutrophils </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stimulates synthesis of metalloproteinases (i.e., trace metal containing enzymes) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stimulates synthesis and release of acute phase reactants from the liver </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CELL</b></td><td align="LEFT" valign="BOTTOM"><b>CHARACTERISTICS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neutrophil (see <span>[[Fig. 2-13|Figure 2-13]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Key cell in acute inflammation. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Receptors for IgG and C3b: important in phagocytosis of opsonized bacteria. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bone marrow neutrophil pools </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mitotic pool: myeloblasts, promyelocytes, myelocytes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Post-mitotic pool: metamyelocytes, band neutrophils (stabs), segmented neutrophils </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral blood neutrophil pools </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Marginating pool: adherent to the endothelium; account for ∼ 50% of peripheral blood pool </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Circulating pool: measured in complete blood cell count (CBC); account for ∼ 50% of peripheral blood pool </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes neutrophilic leukocytosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infections (e.g., acute appendicitis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sterile inflammation with necrosis (e.g., acute myocardial infarction) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drugs inhibiting neutrophil adhesion molecules: corticosteroids, catecholamines, lithium </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Monocytes and macrophages (see <span>[[Figs. 2-14A|Figure 2-14]]</span>; <span>[[12-2D|Figure 12-2]]</span>): </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Key cells in chronic inflammation<br>Receptors for IgG and C3b </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Monocytes become macrophages: fixed (e.g., macrophages in red pulp), wandering (e.g., alveolar macrophages) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Functions: phagocytosis, process antigen, enhance host immunologic response (secrete cytokines like IL-1, TNF) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes of monocytosis: chronic inflammation, autoimmune disease, malignancy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> B cells and T cells (see <span>[[Figs. 2-14B|Figure 2-14]]</span>; <span>[[12-2C|Figure 12-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral blood lymphocyte count: T cells 60-70%, B cells 10-20% of the total<br>B cell function: become plasma cells when antigenically stimulated </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> T cell functions: cellular immunity (type IV HSR), cytokines regulate B cells, defense against intracellular pathogens (e.g., tuberculosis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes of B/T lymphocytosis: viral infections </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Plasma cells (see <span>[[Fig. 2-14C|Figure 2-14]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antibody producing cells derived from B cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Morphology: well-developed rough endoplasmic reticulum (site of protein synthesis). Bright blue cytoplasmic staining with Wright-Giemsa. Nucleus eccentrically located and has perinuclear clearing. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mast cells and basophils (see <span>[[Fig. 12-2B|Figure 12-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Release mediators in acute inflammation and allergic reactions (type I HSR)<br>Receptors for IgE </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Early release reaction: release of preformed mediators (i.e., histamine, chemotactic factors, proteases) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Late phase reaction: new synthesis and release of PGs and LTs, which enhance and prolong the acute inflammatory process. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Eosinophils (see <span>[[Figs. 2-14D|Figure 2-14]]</span>, <span>[[12-2A|Figure 12-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Receptors for IgE<br>Red granules contain crystalline material; become Charcot-Leyden crystals in the sputum of asthmatics. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Preformed chemical mediators in granules </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Major basic protein (MBP) kills invasive helminths. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Histaminase neutralizes histamine. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Arylsulfatase neutralizes leukotrienes. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Functions </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Modulate type I HSR by neutralizing histamine and leukotrienes<br> Destruction of invasive helminths: IgE receptors interact with IgE coating the surface of invasive helminths→ antibody dependent cytotoxicity reaction (type II HSR) causes the release of MBP→ kills helminth </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Destruction of invasive helminths: IgE receptors interact with IgE coating the surface of invasive helminths→ antibody dependent cytotoxicity reaction (type II HSR) causes the release of MBP→ kills helminth </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes of eosinophilia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type I HSR reactions: allergic rhinitis, bronchial asthma. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Invasive helminthic infections <i>excluding</i> pinworms and adult worms in ascariasis, which are not invasive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>HSR, hypersensitivity reaction; IL, interleukin; LT, leukotriene; PG, prostaglandin; TNF, tumor necrosis factor.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TUMOR</b></td><td align="LEFT" valign="BOTTOM"><b>AGE (YEARS)</b></td><td align="LEFT" valign="BOTTOM"><b>MORPHOLOGIC/CLINICAL FINDINGS</b></td><td align="LEFT" valign="BOTTOM"><b>TUMOR MARKER(S)</b></td><td align="LEFT" valign="BOTTOM"><b>PROGNOSIS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Seminoma (see <span>[[Figs. 20-6|Figure 20-6]]</span> and <span>[[20-7|Figure 20-7]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 30-35; >65 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common germ cell tumor (40%)<br>Gray tumor <i>without</i> hemorrhage or necrosis. Large cells with centrally located nucleus containing prominent nucleoli. Lymphocytic infiltrate </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ hCG in 10% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Excellent<br>Extremely radiosensitive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metastasis: lymphatic (para-aortic lymph nodes) <i>before</i> hematogenous (lungs) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Spermatocytic variant occurs in older individuals and rarely metastasizes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Embryonal carcinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 20-25 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bulky tumor with hemorrhage and necrosis. Other tumor types often present<br>Metastasis: hematogenous before lymphatic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ AFP and/or hCG in 90% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intermediate<br>Less radiosensitive than seminomas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Yolk sac (endodermal sinus) tumor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common testicular tumor in children < 4 years old </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Characteristic Schiller-Duval bodies resemble primitive glomeruli </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ AFP in all cases </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Good </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Choriocarcinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 20-30 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most commonly mixed with other tumor types<br>Contains trophoblastic tissue (syncytiotrophoblast and cytotrophoblast) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ hCG in all cases </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Poor<br>Most aggressive tumor; hematogenous spread to lungs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May produce gynecomastia (hCG is an LH analogue) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Teratoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Affects males of all ages </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contains derivatives from ectoderm, endoderm, mesoderm<br>Mixed with embryonal carcinoma (teratocarcinoma) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ AFP and/or hCG in 50% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Good<br>Usually benign in children and malignant in adults (usually squamous cell carcinoma) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant lymphoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common testicular cancer in men > 60 years of age </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secondary involvement of both testes by diffuse large cell lymphoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> None </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Poor </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> </td></tr></tbody></table><a name=""></a> <br>* Listed in order of prognosis.<br>AFP, α-fetoprotein; hCG, human chorionic gonadotropin; LH, luteinizing hormone.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DYSFUNCTION</b></td><td align="CENTER" valign="BOTTOM"><b>TESTOSTERONE</b></td><td align="CENTER" valign="BOTTOM"><b>SPERM COUNT</b></td><td align="CENTER" valign="BOTTOM"><b>LH</b></td><td align="CENTER" valign="BOTTOM"><b>FSH</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> <b>Primary</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Leydig dysfunction </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> N </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Seminiferous tubule dysfunction </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Leydig cell and seminiferous tubule dysfunction </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> <b>Secondary</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypopituitarism </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> </td></tr></tbody></table><a name=""></a> <br>FSH, follicle-stimulating hormone; LH, luteinizing hormone; N, normal.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>PATHOGEN</b></td><td align="LEFT" valign="BOTTOM"><b>DESCRIPTION AND TREATMENT</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Calymmatobacterium granulomatis</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> STD; gram-negative coccobacillus that causes granuloma inguinale </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Organism phagocytized by macrophages (Donovan bodies) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Creeping, raised sore that heals by scarring; no lymphadenopathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: doxycycline or trimethoprim-sulfamethoxazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Candida albicans</i> (see <span>[[Fig. 21-1A|Figure 21-1]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Yeasts and pseudohyphae (elongated yeasts); part of normal vaginal flora </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Second most common vaginitis in the United States </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Risk factors: diabetes, antibiotics, pregnancy, OCP </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pruritic vaginitis with a white discharge and fiery red mucosa </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: fluconazole (single dose) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Chlamydia trachomatis</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> STD; often coexists with <i>Neisseria gonorrhoeae</i> (45% of cases) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Incubation period 7-12 days after exposure; red inclusions (reticulate bodies) in infected metaplastic squamous cells; reticulate bodies divide to form elementary bodies, which are the infective bodies producing infection </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infections in males: NSU (sterile pyuria), epididymitis, proctitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infections in females: urethritis (sterile pyuria), cervicitis, PID, perihepatitis (FHC syndrome-scar tissue between peritoneum and surface of liver from pus from PID), proctitis, Bartholin gland abscess </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infections in newborns: conjunctivitis (ophthalmia neonatorum), pneumonia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> DNA probe test for quick diagnosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: azithromycin 1 g (single dose); doxycycline </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>C. trachomatis</i> subspecies </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> STD; lymphogranuloma venereum </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Papules with no ulceration; inguinal lymphadenitis with granulomatous microabscesses and draining sinuses </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lymphedema of scrotum or vulva; women also may develop rectal strictures </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: doxycycline </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Gardnerella vaginalis</i> (see <span>[[Fig. 21-1B|Figure 21-1]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative rod that causes bacterial vaginosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common vaginitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malodorous vaginal discharge; vaginal pH > 4.5 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Organisms adhere to squamous cells producing "clue cells" </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased incidence of preterm delivery and low-birth-weight newborns </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: metronidazole; same treatment in pregnancy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Haemophilus ducreyi</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> STD; gram-negative rod that causes chancroid </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Male dominant disease (10:1); high incidence of HIV </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Incubation 4-7 days </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Painful genital and perianal ulcers with suppurative inguinal nodes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis with Gram stain ("school of fish" appearance) and culture </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ceftriaxone or azithromycin 1 g (single dose) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HSV-2 (see <span>[[Fig. 21-1C and D|Figure 21-1]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> STD; virus remains latent in sensory ganglia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Recurrent vesicles that ulcerate; locations-penis, vulva, cervix, perianal area </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tzanck preparation: scrapings removed from the base of an ulcer; see multinucleated squamous cells with eosinophilic intranuclear inclusions </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pregnancy: if virus is shedding, baby is delivered by cesarean section </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: acyclovir (decreases recurrences) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HPV (see <span>[[Fig. 21-1E|Figure 21-1]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> STD; types 6 and 11 (90%; low risk types) associated with condyloma acuminata (venereal warts); fernlike or flat lesions in genital area (e.g., penis, vulva, cervix, perianal) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common overall STD; 80% of sexually active women will have acquired HPV by age 50 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Types 16 and 18 (high risk types) associated with dysplasia and squamous cancer </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Virus produces koilocytic change in squamous epithelium </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cells have wrinkled pyknotic nuclei surrounded by a clear halo </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Approximately 90% spontaneously clear within 2 years (most within 8 months); older women will more often have persistent disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vaccine decreases risk for developing cervical cancer </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: topical podophyllin; α-IFN injection; imiquimod cream </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Neisseria gonorrhoeae</i> (see <span>[[Fig. 21-1F|Figure 21-1]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> STD; gram-negative diplococcus that infects glandular or transitional epithelium; symptoms appear 2-7 days after sexual exposure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infection sites similar to <i>C. trachomatis</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complications: ectopic pregnancy, male sterility, disseminated gonococcemia (C6-C9 deficiency risk factor), septic arthritis, FHC syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Disseminated gonococcemia: septic arthritis (knee), tenosynovitis (hands, feet), pustules (hands, feet); more common in women than men </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> DNA probe test for quick diagnosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ceftriaxone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treponema pallidum</i> (see <span>[[Fig. 21-1G, H, and I|Figure 21-1]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> STD; gram-negative spirochete that causes syphilis<br>Primary syphilis: solitary painless, indurated chancre; locations-penis, labia, mouth </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secondary syphilis: maculopapular rash on trunk, palms, soles; generalized lymphadenopathy; condylomata lata, which are flat lesions in same area as condylomata acuminata; alopecia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tertiary syphilis: neurosyphilis, aortitis, gummas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Congenital syphilis (refer to <span macro="tag [[05 Genetic and Developmental Disorders]] [[Chapter 5]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nonspecific screening tests: RPR or VDRL; titers decrease after treatment </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Confirmatory treponemal test: FTA-ABS; positive with or without treatment </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Jarisch-Herxheimer reaction: intensification of rash in primary or secondary syphilis may occur due to proteins released from dead organisms after treatment with penicillin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: penicillin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Trichomonas vaginalis</i> (see <span>[[Fig. 21-1J|Figure 21-1]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> STD; flagellated protozoan with jerky motility </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces vaginitis, cervicitis, and urethritis; strawberry-colored cervix and fiery red vaginal mucosa; greenish, frothy discharge </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: metronidazole (both partners) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>FHC, Fitz-Hugh-Curtis; FTA-ABS, fluorescent treponeme antibody-absorption test; HPV, human papillomavirus; HSV, herpes simplex virus; IFN, interferon; NSU, nonspecific urethritis; OCP, oral contraceptive pill; PCR, polymerase chain reaction; PID, pelvic inflammatory disease; RPR, rapid plasma reagin; STD, sexually transmitted disease; VDRL, Venereal Disease Research Laboratory.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>AGE BRACKET</b></td><td align="LEFT" valign="BOTTOM"><b>CAUSES OF BLEEDING</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prepubertal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vulvovaginitis: poor hygiene, infection (e.g., gonorrhea), sexual abuse, foreign bodies </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Embryonal rhabdomyosarcoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Menarche to 20 years </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anovulatory DUB (most common cause) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Von Willebrand's disease (refer to <span macro="tag [[14 Hemostasis Disorders]] [[Chapter 14]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 20-40 years </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pregnancy and its complications (most common cause) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ovulatory types of DUB </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> PID, hypothyroidism, submucosal leiomyomas, adenomyosis, endometrial polyp, endometriosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ≥40 years </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anovulatory DUB (most common cause in perimenopausal period) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Endometrial hyperplasia/cancer (most common cause in menopause) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>DUB, dysfunctional uterine bleeding; PID, pelvic inflammatory disease.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>FSH/LH</b></td><td align="LEFT" valign="BOTTOM"><b>ESTROGEN</b></td><td align="LEFT" valign="BOTTOM"><b>EXAMPLES</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypothalamic/pituitary disorder </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypopituitarism </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anorexia nervosa, prolactinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ovarian disorder </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Turner's syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> End-organ defect </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Imperforate hymen, Asherman syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Constitutional delay </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Family history of delayed onset of menses </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> </td></tr></tbody></table><a name=""></a> <br>FSH, follicle-stimulating hormone; LH, luteinizing hormone; N, normal.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TUMOR</b></td><td align="LEFT" valign="BOTTOM"><b>CHARACTERISTICS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Surface-Derived Tumors</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serous tumors </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common group of primary benign and malignant tumors </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common group of tumors that can be bilateral </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cysts are lined by ciliated cells (similar to fallopian tube) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serous cystadenoma (benign; most common benign ovarian tumor); serous cystadenocarcinoma has psammoma bodies (dystrophically calcified tumor cells); most common malignant tumor that is bilateral </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mucinous tumors </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cysts lined by mucus-secreting cells (similar to endocervix) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Large, multiloculated tumors </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Seeding produces pseudomyxoma peritonei </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mucinous cystadenoma (benign); may be associated with Brenner tumors; mucinous cystadenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Endometrioid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant tumors associated with endometrial carcinoma (15-30% of cases); tumor resembles endometrial carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Commonly bilateral </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Brenner tumor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Usually benign </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contain Walthard's rests (transitional-like epithelium) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Germ Cell Tumors</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cystic teratoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Usually benign; less than 1% become malignant (usually squamous cancer) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common benign germ cell tumor </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ectodermal differentiation (hair, sebaceous glands, teeth) most prominent </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most of these derivatives are found in a nipple-like structure in the cyst wall called Rokitansky tubercle </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Immature malignant types contain mature and immature components (e.g., muscle, neuroepithelium) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Struma ovarii type has functioning thyroid tissue </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dysgerminoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common malignant germ cell tumor; characteristic increase in serum LDH; same histologic picture as seminoma of testis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with streak gonads of Turner syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Yolk sac tumor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant tumor; most common ovarian cancer in girls < 4 years old </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contain Schiller-Duval bodies (resemble yolk sac) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased α-fetoprotein </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Sex-Cord Stromal Tumors</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thecoma-fibroma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Benign tumor associated with Meigs' syndrome (ascites, right-sided pleural effusion); regression of effusions follows removal of tumor </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Commonly calcify </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Granulosa-theca cell tumor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Low-grade malignant tumor </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Feminizing tumor (produces estrogen) that contains Call-Exner bodies </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sertoli-Leydig cell </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Benign masculinizing tumor (produces androgens) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pure Leydig cell tumors contain cells with crystals of Reinke </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gonadoblastoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant tumor with mixture of germ cell tumor (dysgerminoma) and sex-cord stromal tumor; associated with abnormal sexual development in 80% of cases </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Commonly calcify </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Tumors Metastatic to Ovary</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Krukenberg tumor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May affect both ovaries; contains signet-ring cells from hematogenous spread of a gastric cancer </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>LDH, lactate dehydrogenase.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Noninvasive</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ductal carcinoma in situ (DCIS) (see <span>[[Fig. 21-39A|Figure 21-39]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nonpalpable<br>Patterns: cribriform (sieve-like), comedo (necrotic center) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Commonly contain microcalcifications; cannot be detected by mammogram unless microcalcifications are present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> One third eventually invade </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Treated with "lumpectomy" </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lobular carcinoma in situ (see <span>[[Fig. 21-39B|Figure 21-39]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nonpalpable; virtually always an incidental finding in a breast biopsy for other reasons; cannot be identified by mammography </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lobules distended with bland neoplastic cells; one third eventually invade; usually estrogen and progesterone receptor positive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased incidence of cancer in the opposite breast (50-75%); does <i>not</i> have to be a lobular cancer </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Invasive</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infiltrating ductal carcinoma (see <span>[[Fig. 21-39C and D|Figure 21-39]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stellate morphology, indurated, gray-white tumor<br>One third have amplification of <i>ERBB2</i> oncogene </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gritty on cut section </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Induration caused by reactive fibroplasia (desmoplasia) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Paget's disease of nipple (see <span>[[Fig. 21-39E|Figure 21-39]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Extension of DCIS into lactiferous ducts and skin of nipple producing a rash with or without nipple retraction </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Paget's cells are present </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Palpable mass present in 50-60% </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Medullary carcinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with <i>BRCA1</i> mutations </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bulky, soft tumor with large cells and lymphoid infiltrate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Majority are estrogen and progesterone receptor negative </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inflammatory carcinoma (see <span>[[Fig. 21-39F|Figure 21-39]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Erythematous breast with dimpling like an orange (peau d'orange) due to fixed opening of the sweat glands, which cannot expand with lymphedema </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Plugs of tumor blocking lumen of dermal lymphatics cause localized lymphedema </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Very poor prognosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Combination chemotherapy followed by surgery and irradiation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Invasive lobular carcinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neoplastic cells arranged in linear fashion or form concentric circles (bull's-eye appearance) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tubular carcinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Develops in terminal ductules </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased incidence of cancer in opposite breast (10-40%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Colloid (mucinous) carcinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Usually occurs in elderly women </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neoplastic cells are surrounded by extracellular mucin </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TROPHIC HORMONE DEFICIENCY</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gonadotropins (FSH, LH) (see <span>[[Fig. 22-2A and B|Figure 22-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Children have delayed puberty<br>Adult females have secondary amenorrhea; produces osteoporosis, hot flashes (lack of estrogen), decreased libido </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Males have impotence, due to decreased libido from decreased testosterone (refer to <span macro="tag [[20 Lower Urinary Tract and Male Reproductive Disorders]] [[Chapter 20]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> GnRH stimulation test: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>No</i> significant increase of FSH/LH in hypopituitarism </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Eventual increase of FSH/LH in hypothalamic disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metyrapone test: stimulation test of pituitary ACTH reserve; metyrapone inhibits adrenal 11-hydroxylase, which causes a decrease in cortisol and a corresponding increase in plasma ACTH (pituitary) and 11-deoxycortisol (adrenal), which is proximal to the enzyme block; in hypopituitarism, neither ACTH or 11-deoxycortisol are increased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Growth hormone (GH) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased GH decreases synthesis and release of IGF-1 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Children have growth delay: delayed fusion of epiphyses; bone growth does <i>not</i> match the age of the child </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adults have hypoglycemia: decreased gluconeogenesis; loss of muscle mass; increased adipose around waist </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Arginine and sleep stimulation tests: <i>no</i> increase in GH or IGF-1; normally, GH and IGF-1 are released at 5 am </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thyroid-stimulating hormone (TSH) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secondary hypothyroidism: decreased serum T<sub>4</sub> and TSH<br>Cold intolerance, constipation, weakness </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>No</i> increase in TSH after TRF stimulation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adrenocorticotropic hormone (ACTH) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secondary hypocortisolism: decreased ACTH and cortisol<br>Hypoglycemia: decreased gluconeogenesis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hyponatremia: mild SIADH (loss of inhibitory effect of cortisol on ADH) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Weakness, fatigue </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Short ACTH stimulation test: <i>no</i> increase in serum cortisol over decreased baseline levels </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prolonged ACTH stimulation test: eventual increase in cortisol over the decreased baseline value once the adrenal gland is restimulated </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metyrapone test: no increase in ACTH or 11-deoxycorticosterone (see above gonadotropin discussion) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>ADH, antidiuretic hormone; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; IGF, insulin growth factor; LH, luteinizing hormone; SIADH, syndrome of inappropriate antidiuretic hormone; T<sub>4</sub>, thyroxine; TRF, thyrotropin-releasing factor.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TUMOR</b></td><td align="LEFT" valign="BOTTOM"><b>DESCRIPTION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glucagonoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant tumor of α-islet cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical: hyperglycemia, rash (necrolytic migratory erythema) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: surgery; octreotide (somatostatin analogue) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insulinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Benign tumor of β-islet cells; most common islet cell tumor; approximately 80% have MEN I syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical: fasting hypoglycemia causing mental status abnormalities </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Laboratory: fasting hypoglycemia; increase in serum insulin and C-peptide, which is an endogenous marker of insulin produced in β-islet cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: surgery is the treatment of choice; streptozotocin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Surreptitious injection of insulin: fasting hypoglycemia, increased insulin, <i>decreased</i> C-peptide </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Somatostatinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant tumor of α-islet cells; somatostatin is an inhibitory hormone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibition of gastrin causes achlorhydria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibition of cholecystokinin causes cholelithiasis and steatorrhea </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibition of gastric inhibitory peptide causes diabetes mellitus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibition of secretin causes steatorrhea </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: surgery; streptozotocin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> VIPoma (pancreatic cholera) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant tumor with excessive secretion of vasoactive intestinal peptide (VIP)<br>Clinical: secretory diarrhea, achlorhydria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Laboratory: hypokalemia, normal anion gap metabolic acidosis (loss of bicarbonate in stool) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: surgery; octreotide (somatostatin analogue) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Zollinger-Ellison (refer to <span macro="tag [[17 Gastrointestinal Disorders]] [[Chapter 17]]"></span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant islet cell tumor that secretes gastrin producing hyperacidity; MEN I association (20-30% of cases) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical: peptic ulceration, diarrhea, maldigestion of food </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Laboratory: serum gastrin >1000 pg/mL </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: proton inhibitors; surgery; octreotide (somatostatin analogue) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>MEN, multiple endocrine neoplasia.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CHARACTERISTIC</b></td><td align="LEFT" valign="BOTTOM"><b>TYPE 1</b></td><td align="LEFT" valign="BOTTOM"><b>TYPE 2</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prevalence </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 5-10% </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 90-95% </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Age at onset </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <30 years </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >40 years </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Speed of onset </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rapid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insidious </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Body habitus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Usually thin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Usually obese (80% of cases) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Genetics </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Family history uncommon </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Family history common </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Environmental factors required for expression </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No HLA association<br>Increased in Native Americans and in blacks </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HLA-DR3 and HLA-DR4 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associations </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Other autoimmune diseases: Graves' disease, Hashimoto's thyroiditis, pernicious anemia, Addison's disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No autoimmune associations </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pathogenesis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lack of insulin<br>Pancreas devoid of β-islet cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Relative deficiency of insulin; early stages have hyperinsulinemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insulitis: T-cell cytokine destruction (type IV HSR) and autoantibodies against β-islet cells and insulin (type II HSR) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insulin resistance related to receptor and postreceptor problems<br>Decreased insulin receptors: downregulation by increased adipose </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Triggers for destruction-e.g., viruses<br>Autoantibodies to islet cells (>80%) and insulin (>50%) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Postreceptor defects: most important factor; examples-tyrosine kinase defects, GLUT-4 abnormalities<br>Fibrotic β-islet cells contain amyloid </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No autoantibodies </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical findings </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Polyuria, polydipsia, polyphagia, weight loss </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insidious onset of symptoms<br>Recurrent blurry vision: alteration in lens refraction from sorbitol </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Recurrent infections: bacterial, <i>Candida</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Target organ disease: nephropathy, retinopathy, neuropathy, coronary artery disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Reactive hypoglycemia: too much insulin is released for a glucose load (early finding) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for Alzheimer's disease (refer to <span macro="tag [[25 Nervous System and Special Sensory Disorders]] [[Chapter 25]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ketoacidosis (hyperglycemia, coma; production of ketone bodies); lactic acidosis from shock </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HNKC: enough insulin to prevent ketoacidosis but <i>not</i> enough to prevent hyperglycemia<br>Lactic acidosis may occur due to shock </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Treatment </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insulin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Weight loss: upregulates insulin receptor synthesis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oral hypoglycemic agents; may require insulin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>GLUT, glucose transport unit; HLA, human leukocyte antigen; HNKC, hyperosmolar nonketotic coma; HSR, hypersensitivity reaction.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>COMPLICATION CATEGORY</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Atherosclerotic disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased incidence of strokes, CAD, and peripheral vascular disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute MI is the most common cause of death </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gangrene of the lower extremities; diabetes is the most common cause of nontraumatic amputation of the lower extremity </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal disorders (see <span>[[Fig. 19-7J|Figure 19-7]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal failure due to nodular glomerulosclerosis (refer to <span macro="tag [[19 Kidney Disorders]] [[Chapter 19]]"></span>)<br>Renal papillary necrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ocular disorders (see <span>[[Fig. 22-27|Figure 22-27]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for cataracts and glaucoma<br>Retinopathy (15%): </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Nonproliferative</i>: microaneurysm formation; flame hemorrhages; exudates </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Proliferative</i>: formation of new vessels (neovascularization); increased risk for retinal detachment and blindness; annual ophthalmologic examination is mandatory (photocoagulate microaneurysms) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral nerve disorders (see <span>[[Fig. 22-26|Figure 22-26]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diabetes mellitus is the most common cause of peripheral neuropathy in the United States; occurs in 70-80% </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sensory: paresthesias; patients complain of burning feet; ↓ pinprick sensation; ↓ proprioception (ataxia) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Motor dysfunction: muscle weakness; ↓ deep tendon reflexes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neuropathy is the most important risk factor for pressure ulcers on the bottom of the feet (patient cannot feel pain) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i> for neuropathy: duloxetine (selective serotonin and norepinephrine reuptake inhibitor); topical capsaicin; amitriptyline </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autonomic nervous system disorders </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autonomic neuropathy: gastroparesis (delayed emptying of stomach); impotence; neurogenic bladder; orthostatic hypotension </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i> for gastroparesis: prokinetic agents (e.g., metoclopramide) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cranial nerve (CN) disorders </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diabetes is the most common cause of multiple cranial nerve palsies<br>Cranial nerves most often involved: CN III, IV, and VI </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infectious disorders </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urinary tract infections </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Candida</i> infections: e.g., vulvovaginitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant external otitis due to <i>Pseudomonas aeruginosa</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rhinocerebral mucormycosis: <i>Mucor</i> extends from the frontal sinuses to the frontal lobes, producing infarction (vessel invader) and abscesses </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cutaneous infections: usually <i>Staphylococcus aureus</i> abscesses </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Skin disorders </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Necrobiosis lipoidica diabeticorum: well-demarcated yellow plaques over the anterior surface of the legs/dorsum of ankles </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lipoatrophy: atrophy at insulin injection sites due to impure insulin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lipohypertrophy: increased fat synthesis at insulin injection sites </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Joint disorders </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neuropathic joint: related to lack of sensation; bone or joint deformity from repeated trauma (refer to <span macro="tag [[23 Musculoskeletal and Soft Tissue Disorders]] [[Chapter 23]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>CAD, coronary artery disease; MI, myocardial infarction.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="CENTER" valign="BOTTOM"><b>SERUM T<sub>4</sub></b></td><td align="CENTER" valign="BOTTOM"><b>FREE T<sub>4</sub></b></td><td align="CENTER" valign="BOTTOM"><b>SERUM TSH</b></td><td align="CENTER" valign="BOTTOM"><b><sup>131</sup>I UPTAKE</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Graves' disease </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Patient taking excess hormone </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Initial phase of thyroiditis </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary hypothyroidism </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↔ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secondary hypothyroidism (hypopituitarism) </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↔ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased TBG (e.g., excess estrogen) </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↔ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased TBG (e.g., anabolic steroids) </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> N </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↔ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> </td></tr></tbody></table><a name=""></a> <br>N, normal; T<sub>4</sub>, thyroxine; TBG, thyroid-binding globulin; TSH, thyroid-stimulating hormone; ↔, not indicated.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute pancreatitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Calcium is bound to fatty acids in enzymatic fat necrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Poor prognostic sign </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypovitaminosis D </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lack of sunlight: decreased photoconversion of cholesterol to (nonrenal) vitamin D<sub>3</sub> (cholecalciferol) in the skin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malabsorption (e.g., celiac disease): ↓ reabsorption of fat-soluble vitamin D; ↓ synthesis of 25-(OH)D; ↓ serum calcium causes ↑ serum PTH, which ↑ synthesis of 1,25-(OH)<sub>2</sub>D even though there is a ↓ 25-(OH)D (more enzyme than normal for the conversion); serum phosphorus is usually normal because of the opposing effects of an ↑ serum PTH (phosphaturic effect) and ↑ 1,25-(OH)<sub>2</sub>D, increases bowel reabsorption of phosphorus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cirrhosis: decreased synthesis of 25-(OH)D; similar findings to malabsorption regarding calcium, phosphorus, PTH, and 1,25-(OH)<sub>2</sub>D </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drugs enhancing cytochrome system (e.g., alcohol, phenytoin): increased metabolism of 25-(OH)D into an inactive metabolite; hence, ↓ 25-(OH)D → ↓ 1,25-(OH)<sub>2</sub>D </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic renal failure: ↓ synthesis of 1,25-(OH)<sub>2</sub>D (↓ 1α-hydroxylation); 25-(OH)D normal or slightly ↓; ↓ serum calcium, ↑ serum phosphorus, ↑ serum PTH </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vitamin D-dependent rickets </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Autosomal recessive type I:</i> absent 1α-hydroxylase, so ↓ 1,25-(OH)<sub>2</sub>D; normal 25-(OH)D, ↓ serum calcium, normal to ↓ serum phosphorus, ↑ serum PTH </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Treatment: calcitriol </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Autosomal recessive type II:</i> absent receptors for calcitriol, so calcitriol cannot function properly; ↑ 1,25-(OH)<sub>2</sub>D, normal 25-(OH)D, ↓ serum calcium, normal to ↓ serum phosphorus, ↑ serum PTH </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pseudohypoparathyroidism (see <span>[[Fig. 22-16|Figure 22-16]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal dominant disease<br>End-organ resistance to PTH (includes its ability to synthesize 1α-hydroxylase in the proximal tubule) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mental retardation, basal ganglia calcification, short fourth and fifth metacarpals ("knuckle-knuckle-dimple-dimple" sign) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypocalcemia, normal to ↑ PTH; normal 25-(OH)D, ↓ 1,25-(OH)<sub>2</sub>D </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>25-(OH)D, calcidiol; 1,25-(OH)<sub>2</sub>D, calcitriol; PTH, parathyroid hormone.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypervitaminosis D </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased calcium reabsorption in the jejunum and kidneys </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignancy-induced </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mechanisms: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bone metastasis with local activation of osteoclasts (most common): produces lytic lesions in bone; ↓ serum PTH; normal 25-(OH)D, ↓ 1,25-(OH)<sub>2</sub>D (↓ PTH, therefore no 1α-hydroxylase) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ectopic secretion of a PTH-related protein (squamous cell carcinoma of lung, renal cell carcinoma): generalized activation of osteoclasts <i>without</i> producing lytic lesions in bone; uses the same receptor site as PTH to perform its functions; ↓ serum PTH; normal 25-(OH)D, ↓ 1,25-(OH)<sub>2</sub>D (no 1α-hydroxylase) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Multiple myeloma: localized increased secretion of osteoclast-activating factor (IL-1) by malignant plasma cells; produces lytic lesions in bone; ↓ serum PTH; normal 25-(OH)D, ↓ 1,25-(OH)<sub>2</sub>D (no 1α-hydroxylase) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Familial hypocalciuric hypercalcemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal dominant with 100% penetrance </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mutation causing altered set-point for calcium-sensing receptor on renal tubule and parathyroid gland; normal to slightly increased serum PTH but very low urinary calcium levels (increased in primary hyperparathyroidism) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sarcoidosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mechanism: macrophages in granulomas synthesize 1α-hydroxylase, causing hypervitaminosis D </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thiazides </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mechanism: volume depletion increases renal tubule reabsorption of calcium; always consider a possible underlying parathyroid adenoma (order serum intact PTH) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>IL, interleukin; 25-(OH)D, calcidiol; 1,25-(OH)<sub>2</sub>D, calcitriol; PTH, parathyroid hormone.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypovitaminosis D (extrarenal causes) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased reabsorption of phosphorus from the small intestine and kidneys </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insulin Rx in DKA </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased uptake of glucose into cells requires phosphorus for phosphorylation (traps glucose in the cell) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary HPTH </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased PTH decreases phosphorus reabsorption in the proximal tubules </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> PTH-related peptide </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Uses same receptor as PTH; decreases phosphorus reabsorption in the proximal tubules </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Respiratory/metabolic alkalosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alkalosis activates phosphofructokinase, the rate-limiting reaction of glycolysis, causing increased phosphorylation of glucose; most common cause of hypophosphatemia in the hospital </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vitamin D-resistant rickets </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> X-linked dominant disorder </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Defect in renal and gastrointestinal reabsorption of phosphorus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>DKA, diabetic ketoacidosis; HPTH, hyperparathyroidism; PTH, parathyroid hormone; Rx, treatment.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER/CONDITION</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic renal failure (most common cause) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased excretion of phosphorus as titratable acid </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal child </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Children require increased serum phosphorus to drive calcium into bone for mineralization </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary hypoparathyroidism </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased excretion of phosphorus as titratable acid </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pseudohypoparathyroidism </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal dominant disease (see <span>[[Table 22-3|Table 22-3. OTHER CAUSES OF HYPOCALCEMIA]]</span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> End-organ resistance to PTH (includes its ability to synthesize 1α-hydroxylase in the proximal tubule) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>PTH, parathyroid hormone.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>LABORATORY MEASUREMENT</b></td><td align="CENTER" valign="BOTTOM"><b>21-OHASE DEFICIENCY</b></td><td align="CENTER" valign="BOTTOM"><b>11-OHASE DEFICIENCY</b></td><td align="CENTER" valign="BOTTOM"><b>17-OHASE DEFICIENCY</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 17-Ketosteroids </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 17-Hydroxyprogesterone </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 17-Hydroxycorticoids </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mineralocorticoids </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="CENTER" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> </td></tr></tbody></table><a name=""></a> <br>OHase, hydroxylase.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>LABORATORY TEST</b></td><td align="LEFT" valign="BOTTOM"><b>PITUITARY CS</b></td><td align="LEFT" valign="BOTTOM"><b>ADRENAL CS</b></td><td align="LEFT" valign="BOTTOM"><b>ECTOPIC CS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Serum cortisol </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urine free cortisol </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Low-dose dexamethasone </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cortisol <i>not</i> suppressed </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cortisol <i>not</i> suppressed </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cortisol <i>not</i> suppressed </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> High-dose dexamethasone </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cortisol suppressed </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cortisol <i>not</i> suppressed </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cortisol <i>not</i> suppressed </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Plasma adrenocorticotropic hormone (ACTH) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> "Normal"* to ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Markedly ↑ </td></tr></tbody></table><a name=""></a> <br>*"Normal": a plasma ACTH in the normal range is <i>not</i> normal in the presence of an increase in serum cortisol.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TUMOR TYPE</b></td><td align="LEFT" valign="BOTTOM"><b>EPIDEMIOLOGY</b></td><td align="LEFT" valign="BOTTOM"><b>PRIMARY LOCATION</b></td><td align="LEFT" valign="BOTTOM"><b>CHARACTERISTICS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> <b>Benign</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osteochondroma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Males, 10-30 yr<br>Solitary or multiple </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metaphysis of distal femur </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Outgrowth of bone (exostosis) capped by benign cartilage<br>Most common benign tumor </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Enchondroma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Equal distribution, 20-50 yr<br>Solitary or multiple </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Medullary location<br>Small tubular bones in hands and feet </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Multiple enchondromas<br>Risk for chondrosarcoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osteoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Males, any age </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Facial bones </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with Gardner's polyposis syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osteoid osteoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Males, 10-20 yr </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cortex of proximal femur </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Radiographic finding: radiolucent focus surrounded by sclerotic bone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nocturnal pain relieved by aspirin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osteoblastoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Males, 10-20 yr </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vertebra </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Similar to osteoid osteoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Giant cell tumor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Females, 20-40 yr </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Epiphysis of distal femur or proximal tibia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Reactive multinucleated giant cells resemble osteoclasts </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neoplastic mononuclear cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> <b>Malignant</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chondrosarcoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Males, 30-60 yr </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pelvic bones, proximal femur </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Grade determines biologic behavior </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metastasizes to lungs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osteogenic sarcoma (see <span>[[Fig. 8-1F|Figure 8-1]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Males, 10-25yr<br>Risk factors: Paget's disease, familial retinoblastoma, irradiation, fibrous dysplasia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metaphysis of distal femur, proximal tibia<br>Most common primary bone cancer (some authors say multiple myeloma) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant osteoid<br>Radiographic findings: "sun-burst" appearance (spiculated pattern from calcified malignant osteoid)<br>"Codman's triangle" (tumor lifting the periosteum)<br>Metastasizes to lungs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ewing's sarcoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Males, 10-20yr </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pelvic girdle, diaphysis and metaphysis of proximal femur or rib </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small, round cell tumor<br>Radiographic finding: "onionskin" appearance around bone (periosteal reaction) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Possible fever and anemia </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TUMOR TYPE</b></td><td align="LEFT" valign="BOTTOM"><b>LOCATION</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENT</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lipoma (see <span>[[Fig. 8-1B|Figure 8-1]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Trunk, neck, proximal extremities </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common benign soft tissue tumor<br>Arises in subcutaneous tissue </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>No</i> clinical significance </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Liposarcoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thigh, retroperitoneum </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common adult sarcoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lipoblasts identified with fat stains </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fibrosarcoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thigh, upper limb </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May arise after irradiation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dermatofibroma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lower extremities </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Benign, nonencapsulated proliferation of spindle cells confined to the dermis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Red nodule that umbilicates (has a central dimple) when squeezed </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant fibrous histiocytoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Retroperitoneum, thigh </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with radiation therapy and scarring </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rhabdomyoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Heart, also tongue and vagina </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Benign heart tumor associated with tuberous sclerosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Embryonal rhabdomyosarcoma (see <span>[[Fig. 21-4|Figure 21-4]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Penis and vagina </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common sarcoma in children<br>Grape-like, necrotic mass protrudes from penis or vagina </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Leiomyoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Uterus, stomach </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most commonly located in uterus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common benign tumor in gastrointestinal tract </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Leiomyosarcoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastrointestinal tract, uterus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common sarcoma of gastrointestinal tract and uterus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neurofibrosarcoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Major nerve trunks </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with neurofibromatosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Synovial sarcoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Around joints </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Does not arise from synovial cells in joints but from mesenchymal cells around joints </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Biphasic pattern: epithelial cells forming glands + intervening spindle cells </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Colles' fracture (see <span>[[Fig. 23-24A|Figure 23-24]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common fracture when falling on outstretched hand </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fracture of distal radius with or without fracture of ulnar styloid </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rotator cuff tear </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Components: tendon insertions of supraspinatus, infraspinatus, teres minor, subscapularis muscles </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pain/weakness with active shoulder abduction </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: arthrography; MRI </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: physical therapy; arthroscopic surgery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tennis elbow </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: racquet sports, repetitive use of a hammer or screwdriver </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pain where extensor muscle tendons insert near the lateral epicondyle (lateral epicondylitis); pain when gripping something </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: NSAIDs; rest; local injection with corticosteroids; localized pressure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Golfer's elbow </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pain where the flexor muscle tendons insert near the medial epicondyle (medial epicondylitis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pain duplicated by flexing hand muscles and supinating the arm (arm wrestling movement) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: NSAIDs; rest; local injection with corticosteroids; localized pressure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> DeQuervain's tenosynovitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic stenosing tenosynovitis of the first dorsal compartment of the wrist; overuse of the hands and wrist; first dorsal compartment has abductor pollicis longus and extensor pollicis brevis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Excessive friction thickens tendon sheath causing stenosis of the osseofibrous tunnel </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pain on the ulnar aspect of the wrist aggravated by moving the thumb </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Finkelstein's test: patient puts thumb in the palm, closes fist, tilt hand toward little finger (ulnar deviation); pain occurs in first dorsal compartment </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroid injection; spica splint </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ganglion (synovial) cyst (see <span>[[Fig. 23-24B|Figure 23-24]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bulge on the dorsum of the wrist when the wrist is flexed<br>More common in women than in men </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cyst communicates with synovial sheaths on the dorsum of the wrist </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: aspiration; excision by arthroscopy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Compartment syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increase of pressure in a confined space (fascial compartment); pressure reduces perfusion, which may cause ischemic contractures of the muscle(s) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common locations anterior and posterior compartments in the leg; forearm muscle compartment </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 5 Ps: <i>p</i>ain, <i>p</i>aresthesias, <i>p</i>allor, <i>p</i>aralysis, <i>p</i>ulselessness </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Risk factors: fractures, injuries to arteries/soft tissue; excessive use of the muscles (cyclists; arm wrestlers) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Volkmann's ischemic contracture: displaced supracondylar fracture of distal humerus causing compression of brachial artery and median nerve; forearm muscles (superficial and deep flexor muscles) may undergo contracture; although most of the muscles are innervated by the median nerve, the flexor carpi ulnaris is innervated by the ulnar nerve </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: measure pressures </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: fasciotomy if pressure cannot be relieved with supportive therapy (ice packs) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Carpal tunnel syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Entrapment syndrome of the median nerve in the transverse carpal ligament of the wrist </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: rheumatoid arthritis and pregnancy most common causes; obesity, excessive use of hands, acromegaly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pain, numbness, or paresthesias in the thumb, index finger, 2nd finger, 3rd finger, and the radial side of 4th finger; thenar atrophy produces "ape hand" appearance </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: nerve conduction; electromyography </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Phalen's maneuver</i>: gently flexing of the wrist as far as possible and holding this position reproduces the findings within 1 minute </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Tinel's sign</i>: light tapping over the transverse carpal ligament produces numbness and tingling in the median nerve </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: wrist splint at night; corticosteroid injection; surgery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intervertebral disk disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Degeneration of fibrocartilage/nucleus pulposus; ruptured disk material may herniate posteriorly and compress the nerve root and/or spinal cord </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Radicular pain; leg pain aggravated by straight leg raising </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Herniation of L3-L4 disk: loss of knee jerk (femoral nerve L2-L4) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Herniation of L4-L5 disk: no loss of reflexes (ankle and knee reflexes intact) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Herniation of L5-S1 disk: loss of ankle reflex (tibial nerve L4-S3) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: physical therapy; traction; surgery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Knee joint injuries (see <span>[[Fig. 23-24C|Figure 23-24]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Valgus injury: angulation away from the midline<br>Laterally originating force is applied to the knee (e.g., clipping injury in football) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Varus injury: angulation toward the midline </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Medially originating force is applied to the knee </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> McMurray test: meniscus injuries </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anterior and posterior draw test: cruciate injuries </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> "Unhappy triad": most common internal derangement of knee joint </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Valgus injury; damage to medial meniscus, medial collateral ligament, anterior cruciate ligament </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: physical therapy; arthroscopic surgery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Scoliosis (see <span>[[Fig. 23-24D|Figure 23-24]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lateral curvature of the spine (S- or C-shaped on x-ray) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Congenital, idiopathic, related to another disease (e.g., cerebral palsy) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Idiopathic type: usually affects adolescent girls between 10 and 16 years of age; usually a right thoracic curve; forward bending causes a paraspinous prominence on the right from a hump in the ribs due to a rotational component of the vertebra </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: bracing; surgery </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TERM</b></td><td align="LEFT" valign="BOTTOM"><b>DEFINITION</b></td><td align="LEFT" valign="BOTTOM"><b>EXAMPLE</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>Macroscopic</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macule </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pigmented or erythematous flat lesion on epidermis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tinea versicolor </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Papule </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peaked or dome-shaped surface elevation < 5 mm in diameter </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acne vulgaris </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nodule </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Elevated, dome-shaped lesion > 5 mm in diameter </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Basal cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Plaque </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Flattened, elevated area on epidermis > 5 mm in diameter </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Psoriasis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vesicle </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fluid-filled blister < 5 mm in diameter </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Varicella (chickenpox) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bulla </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fluid-filled blister > 5 mm in diameter </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bullous pemphigoid </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pustule </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fluid-filled blister with inflammatory cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Impetigo </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wheal (hive) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Edematous, transient papule or plaque caused by infiltration of dermis by fluid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urticaria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Scales </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Excessive number of dead keratinocytes produced by abnormal keratinization </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Seborrheic dermatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>Microscopic</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hyperkeratosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased thickness of stratum corneum produces scaly appearance of skin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Psoriasis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Parakeratosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Persistence of nuclei in stratum corneum layer </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Psoriasis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Papillomatosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Spire-like projections from surface of skin or downward into papillary dermis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Verruca vulgaris </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acantholysis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of cohesion between keratinocytes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pemphigus vulgaris </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CSF FEATURE</b></td><td align="LEFT" valign="BOTTOM"><b>BACTERIAL/FUNGAL</b></td><td align="LEFT" valign="BOTTOM"><b>VIRAL</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Total cell count </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 1000-20,000 cells/mm<sup>3</sup> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <1000 cells/mm<sup>3</sup> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Differential count </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >90% neutrophils (>80%) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> First 24-48 hours, neutrophils, then switches to lymphocytes/monocytes after 48 hours </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CSF glucose </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased (<40 mg/dL) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal: exceptions-mumps, herpes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CSF protein </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased (>50 mg/dL) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram stain </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Frequently positive (60-90%) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Negative </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Culture positive (65-90%) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>VIRUS</b></td><td align="LEFT" valign="BOTTOM"><b>DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Arboviruses </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Encephalitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mosquitoes are the vector </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wild birds are the reservoir for the virus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> West Nile virus: crows and other birds have spread the disease from New York to the West Coast </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Encephalitis can be fatal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Coxsackievirus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Meningitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Enterovirus: most common cause of viral meningitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Viral meningitis peaks in late summer and early autumn </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cytomegalovirus (see <span>[[Fig. 25-24A|Figure 25-24]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Encephalitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common viral CNS infection in AIDS<br>Primarily intranuclear basophilic inclusions </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Periventricular calcification in newborns </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ganciclovir + foscarnet; or valganciclovir </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Herpes simplex virus type 1 (see <span>[[Fig. 25-24B|Figure 25-24]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Meningitis and encephalitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes hemorrhagic necrosis of temporal lobes<br><i>Treatment</i>: IV acyclovir </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HIV (see <span>[[Fig. 25-24C|Figure 25-24]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Encephalitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of AIDS dementia<br>Microglial cells fuse to form multinucleated cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lymphocytic choriomeningitis Meningitis and encephalitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Endemic in the mouse population<br>Transmission: food or water contaminated with mouse urine/feces<br>Meningoencephalitis: combination of nuchal rigidity and mental status abnormalities (encephalitis) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CSF findings: increased protein, lymphocyte infiltrate, normal to decreased glucose </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Poliovirus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Encephalitis and myelitis-spinal cord </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Destroys upper and lower motor neurons<br>Causes muscle paralysis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Post-polio syndrome: occurs in ∼ 50% of people with previous poliomyelitis; usually occurs 15-30 years after original infection; increased muscular weakness/pain in muscle groups already affected; excessive fatigue </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rabies virus (see <span>[[Fig. 25-24D|Figure 25-24]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Encephalitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most often transmitted by raccoon bite (40% of cases)<br>Other vectors are dog, skunk, bat, and coyote </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Viral receptor is acetylcholine receptor </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Initially replicates at site of the bite; moves by axonal transport to the CNS; after CNS replication, it migrates to the saliva </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Animal transmits virus when in the agitated state (encephalitis stage) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Incubation period 10-90 days </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prodrome: fever, paresthesias in and around the wound site </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hydrophobia: due to spasms of throat muscles when swallowing </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Followed by flaccid paralysis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Encephalitis: death of neurons; eosinophilic intracytoplasmic inclusions called Negri bodies; seizures, coma, death </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: wash wound site (quaternary ammonium compound); give passive immunization (immune globulin) mostly into wound site (where virus initially replicates); give active immunization (human diploid vaccine) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Universally fatal if <i>not</i> treated </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Creutzfeldt-Jakob disease (see <span>[[Fig. 25-25|Figure 25-25]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Unconventional slow virus encephalitis due to prions (proteinaceous material devoid of RNA or DNA); noninfectious prion protein normally found on surface of neurons (function unknown) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transmitted by corneal transplantation, contact with human brain, use of improperly sterilized cortical electrodes, or ingestion of tissues from cattle with bovine spongiform encephalopathy ("mad cow" disease) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Brain has "bubble and holes" spongiform change in cerebral cortex </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Death usually occurs within 1 year </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Progressive multifocal leukoencephalopathy </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Conventional slow virus encephalitis due to papovavirus<br>Intranuclear inclusion in oligodendrocytes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs in AIDS when CD<sup>4</sup> T<sub>H</sub> count < 50 cells/mm<sup>3</sup> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Subacute sclerosing panencephalitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Conventional slow virus encephalitis associated with rubeola (measles) virus<br>Intranuclear inclusions in neurons and oligodendrocytes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Death usually occurs within 1-2 years </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>BACTERIUM</b></td><td align="LEFT" valign="BOTTOM"><b>DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Group B streptococcus (<i>Streptococcus agalactiae</i>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neonatal meningitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive coccus<br>Most common cause of neonatal meningitis (49%)<br>Spreads from a focus of infection in maternal vagina<br><i>Empiric treatment</i> (culture negative): ampicillin + cefotaxime </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Specific treatment</i>: penicillin G or ampicillin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Escherichia coli</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neonatal meningitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative rod<br>Second most common cause of neonatal meningitis (18%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Empiric treatment</i> (culture negative): ampicillin + cefotaxime </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Specific treatment</i>: ceftazidime + gentamicin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Listeria monocytogenes</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neonatal meningitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive rod with tumbling motility; actin rockets help organism to move from cell to cell </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pathogen found in soft cheese, hot dogs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Empiric treatment</i> (culture negative): ampicillin + cefotaxime </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Specific treatment</i>: ampicillin ± gentamicin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Neisseria meningitidis</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Meningitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-negative diplococcus; locates in posterior nasopharynx<br>Most common cause of meningitis in those between 1 month and 18 years of age </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ceftriaxone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prophylaxis for people in close contact: ciprofloxacin or rifampin or ceftriaxone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Streptococcus pneumoniae</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Meningitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gram-positive diplococcus<br>Most common cause of meningitis in patients > 18 years of age (some authors say <i>N. meningitidis</i> is the most common and <i>S. pneumoniae</i> the 2nd most common) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: penicillin G or ampicillin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Mycobacterium tuberculosis</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Meningitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complication of primary tuberculosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Involves base of brain </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vasculitis (infarction) and scarring (hydrocephalus) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: isoniazid, rifampin, ethambutol, pyrazinamide, dexamethasone (prevent scarring) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treponema pallidum</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Meningitis, encephalitis, myelitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Spirochete<br>Types of neurosyphilis: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Meningovascular: vasculitis causing strokes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> General paresis: dementia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tabes dorsalis: involves posterior root ganglia and posterior column; causes ataxia, loss of vibration sensation, absent deep tendon reflexes, Argyll-Robertson pupil (pupils accommodate but do <i>not</i> react) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: penicillin G (difficult to treat) </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>FUNGUS/PARASITE</b></td><td align="LEFT" valign="BOTTOM"><b>DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Cryptococcus neoformans</i> (see <span>[[Fig. 25-25A|Figure 25-25]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Meningitis and encephalitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs in immunocompromised host<br>Most common fungal CNS infection in AIDS<br>Budding yeasts visible with India ink </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: fluconazole non-AIDS, amphotericin + flucytosine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Mucor</i> species (see <span>[[Fig. 25-25B|Figure 25-25]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Frontal lobe abscess </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs in diabetic ketoacidosis; spreads from frontal sinuses<br><i>Treatment</i>: amphotericin B </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Naegleria fowleri</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Meningoencephalitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protozoa (amoeba) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Involves frontal lobes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted by swimming in freshwater lakes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: amphotericin B </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Trypanosoma gambiense</i>/<i>rhodesiense</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Encephalitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protozoa (hemoflagellate)<br>Transmission: bite of an infected tsetse fly (<i>Glossina</i>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Trypanosomes invade the blood and lymphatics early in the disease; initial drainage into the posterior cervical nodes produces lymphadenopathy (Winterbottom's sign); encephalitis occurs in later stages </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diffuse encephalitis: somnolence ("sleeping sickness") due to the release of sleep mediators by the organisms </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Trypanosomes are capable of antigen variation (cyclical fever spike) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Starvation is the most common cause of death </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: trypanosomes in blood, CSF; serologic tests; characteristic increase in IgM early in the disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: pentamidine early in the disease; melarsoprol in encephalitis stage </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Taenia solium</i> (see <span>[[Fig. 25-25C|Figure 25-25]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cysticercosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Helminth (tapeworm; cestode); pig transmitted disease<br>Patient (intermediate host) ingests food or water containing eggs; eggs develop into larval forms (cysticerci) that invade brain, producing calcified cysts causing seizures; hydrocephalus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: albendazole + dexamethasone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Toxoplasma gondii</i> (see <span>[[Fig. 25-25D and E|Figure 25-25]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Encephalitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Protozoa (sporozoan)<br>Most common CNS space-occupying lesion in AIDS; ring-enhancing lesions on CT </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Congenital toxoplasmosis produces basal ganglia calcification </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: pyrimethamine + sulfadiazine + folinic acid (leucovorin) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>AIDS, acquired immunodeficiency syndrome; CNS, central nervous system; CT, computed tomography.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>INJURY</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ulnar nerve (C8-T1) (see <span>[[Fig. 25-39A|Figure 25-39]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fracture of medial epicondyle of the humerus<br>Injury produces a "claw hand" (loss of interosseous muscles) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Radial nerve (C5-T1) (see <span>[[Fig. 25-39B|Figure 25-39]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Midshaft fractures of humerus<br>Draping the arm over a park bench (called "Saturday night palsy") </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Injury produces wrist drop </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Axillary nerve (C5-6) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fracture of surgical neck of humerus; anterior dislocation of the shoulder joint (may also injure the axillary artery) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cannot abduct the arm to horizontal position or hold the horizontal position when a downward force is applied to the arm (paralysis of deltoid muscle) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Median nerve (C6-T1) (see <span>[[Fig. 25-39C and D|Figure 25-39]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most commonly due to entrapment in the transverse carpal ligament of the wrist or between the bellies of the pronator teres muscle<br>Rheumatoid arthritis and pregnancy two most common causes; also overuse of hands and wrist (e.g., in barbers), amyloidosis, hypothyroidism, supracondylar fracture of humerus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clinical: nocturnal pain; pain, numbness, or paresthesias in the thumb, index finger, third finger, and radial side of fourth finger; thenar atrophy produces an "ape" hand" appearance and difficulty in opposing the thumb with the 5th finger </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tinel's sign: pain reproduced by tapping over the median nerve </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Phalen's sign: pain reproduced with forced flexion of the wrist for 1 minute </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diagnosis: nerve conduction studies; electromyography to rule out muscle degeneration related to nerve compression </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common peroneal nerve (L4-S2) (see <span>[[Fig. 25-39E|Figure 25-39]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common peripheral neuropathy; lead poisoning; fractured neck of the fibula; cast tightness<br>Motor deficits: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of foot eversion due to weakening of the peroneus longus and brevis muscles </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of foot dorsiflexion due to weakening of the tibialis anterior muscle produces "slapping gait" or "high-stepping gait" like a horse </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of toe extension due to weakening of the extensor digitorum longus and hallucis longus muscles </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Combined effect of all the above produces an equinovarus deformity, where there is plantar flexion with foot drop and inversion of the foot </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sensory deficits involve the anterolateral aspect of the leg and dorsum of the foot </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of the ankle jerk reflex </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Erb-Duchenne palsy (see <span>[[Fig. 25-39F|Figure 25-39]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Brachial plexus lesion involving C5 and C6<br>"Waiter's tip deformity" </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>EYE DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Arcus senilis (see <span>[[Fig. 25-40A|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most often occurs in elderly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gray-opaque ring at the corneal margin (periphery of cornea) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cholesterol deposits in corneal stroma; may indicate hypercholesterolemia if patient is <50 years old and a smoker </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ophthalmia neonatorum </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Conjunctivitis in newborn </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pathogens: <i>Neisseria gonorrhoeae</i> (first week; 2-4 days), <i>Chlamydia trachomatis</i> (second week; 3-10 days) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>N. gonorrhoeae</i>: ceftriaxone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>C. trachomatis</i>: erythromycin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Erythromycin eye drops (chemical irritation) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bacterial conjunctivitis (see <span>[[Fig. 25-40B|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Purulent conjunctivitis; pain but <i>no</i> blurry vision<br>Pathogens: <i>Staphylococcus aureus</i> (most common), <i>Streptococcus pneumoniae, Haemophilus influenzae</i> (<i>H. aegyptius,</i> pink eye) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: gatifloxacin ophthalmic solution </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Viral conjunctivitis (see <span>[[Fig. 25-40C|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Watery exudates </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenovirus: viral cause of pink eye, preauricular lymphadenopathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No treatment </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HSV-1: keratoconjunctivitis with dendritic ulcers noted with fluorescein staining </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: trifluridine ophthalmic </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Allergic conjunctivitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Seasonal itching of eyes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: antihistamine ophthalmic solutions; olopatadine (mast cell stabilizer) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Acanthamoeba</i> infection </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Severe keratoconjunctivitis in patients who do not clean their contact lenses properly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: propamidine + polymyxin/neomycin/gramicidin ophthalmic </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stye (see <span>[[Fig. 25-40D|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infection of eyelid most commonly due to <i>S. aureus</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: hot packs + dicloxacillin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chalazion (see <span>[[Fig. 25-40E|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Granulomatous inflammation involving the meibomian gland in the eyelid; usually disappear on their own within 2 months </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: if do not disappear; intralesional corticosteroid injection or surgical removal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Orbital cellulitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Periorbital redness and swelling that is often secondary to sinusitis (e.g., ethmoiditis in children) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pathogens: <i>S. pneumoniae, H. influenzae</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fever, proptosis (eye bulges out), periorbital swelling, ophthalmoplegia (eye movement impaired), normal retinal examination </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: nafcillin + ceftriaxone + metronidazole </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Orbital fracture (see <span>[[Fig. 25-40F|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most often associated with blunt trauma to the eye that produces an orbital floor fracture </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Often associated with edema and ecchymoses of the eyelids and periorbital region ("raccoon" eyes) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vertical diplopia, prolapse of orbital contents into the maxillary sinus (sunken eye), damage to infraorbital nerve may occur in severe fractures </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: varies according to degree of severity </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pterygium </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Raised, triangular encroachment of thickened conjunctiva on the nasal side of the conjunctiva; may grow onto cornea </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Due to excessive exposure to wind, sun, and sand </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: surgical removal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pinguecula (see <span>[[Fig. 25-40G|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Yellow-white conjunctival degeneration at the junction of cornea and sclera on the temporal side of the conjunctiva </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Does not grow onto the cornea like a pterygium does </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Usually requires no treatment </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Optic neuritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inflammation of optic nerve </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: multiple sclerosis (most common), methanol poisoning </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Blurry vision or loss of vision, may cause optic atrophy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Central retinal artery occlusion (see <span>[[Fig. 25-40H|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: embolization of plaque material from ipsilateral carotid or ophthalmic artery; giant cell temporal arteritis involving the ophthalmic artery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sudden, painless, complete loss of vision in one eye, pallor of optic disk due to narrowed arteries, "boxcar" segmentation of blood in retinal veins, cherry red macula </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: acetazolamide to lower intraocular pressure; carbogen (CO<sub>2</sub> dilates + O<sub>2</sub>); hyperbaric O<sub>2</sub> therapy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Central retinal vein occlusion (see <span>[[Fig. 25-40I|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: hypercoagulable state (e.g., polycythemia vera) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sudden, painless, unilateral loss of vision, swelling of optic disk, engorged retinal veins with hemorrhage ("blood and thunder" appearance) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: intravitreal injections; laser photocoagulation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glaucoma (see <span>[[Fig. 25-40J|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased intraocular pressure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Chronic open angle type:</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased rate of aqueous outflow into the canal of Schlemm; bilateral aching eyes; pathologic cupping of optic disks; night blindness and gradual loss of peripheral vision leading to tunnel vision and blindness </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: 1st: β-blockers (e.g., timolol; decrease rate of flow into eye); 2nd: prostaglandins, α-adrenergic agonists, pilocarpine, carbonic anhydrase inhibitors; if drugs fail, laser trabeculoplasty </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Acute angle-closure type:</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Due to narrowing of anterior chamber angle, precipitated by mydriatic agent, uveitis, lens dislocation; severe pain associated with photophobia and blurry vision; red eye with a steamy cornea; pupil fixed and nonreactive to light </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: pilocarpine + systemic carbonic anhydrase inhibitor to lower pressure to allow for laser surgery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Optic nerve atrophy (see <span>[[Fig. 25-40K|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pale optic disk </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most commonly due to optic neuritis or glaucoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No effective treatment </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Uveitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inflammation of uveal tract (iris, ciliary body, choroid) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: sarcoidosis, ulcerative colitis, ankylosing spondylitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pain with blurry vision, miotic pupil, circumcorneal ciliary body vascular congestion, normal intraocular pressure, adhesions between iris and anterior lens capsule </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroids (oral or topical), atropine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macular degeneration (see <span>[[Fig. 25-40L|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of permanent visual loss in the elderly. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Disruption of Bruch's membrane in the retina </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Dry type</i>: thinning of retina and formation of yellowish white deposits called drusen </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Wet type</i>: extension of dry type; vessels under retina hemorrhage causing retinal cells to die, creating blind spots or distorted central vision </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antioxidants may decrease risk </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: antiangiogenics (drugs that block vascular growth factors); insertion of special intraocular lens </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CMV retinitis (see <span>[[Fig. 25-40M|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of blindness in AIDS; usually occurs when CD4 T helper cell count < 50 cells/μL </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cotton-wool exudates and retinal hemorrhages </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: oral, IV, intraocular ganciclovir or foscarnet </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cataracts (see <span>[[Fig. 25-40N|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Opacity in the lens </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: advanced age (most common), diabetes mellitus (osmotic damage), infection (e.g., rubella), corticosteroids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common in congenital infections (e.g., CMV, rubella) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: cataract extraction </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant tumors (see <span>[[Fig. 25-40O|Figure 25-40]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Retinoblastoma in children ("white eye reflex") </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant melanoma in adults </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: enucleation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>CMV, cytomegalovirus; HSV, herpes simplex virus.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>EAR DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>DESCRIPTION AND COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Meniere's disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased endolymph in inner ear and loss of cochlear hairs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dizziness, vertigo, tinnitus, sensorineural hearing loss </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: hydrochlorothiazide + triamterene; surgery in resistant cases </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sensorineural defect </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Weber test: lateralizes to normal ear (contralateral ear is affected) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rinne test: air conduction > bone conduction in both normal and affected ear </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Presbycusis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of sensorineural hearing loss in elderly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Due to degeneration of cochlear hairs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: amplification devices; cochlear implants </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Otosclerosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of conduction deafness in elderly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Due to fusion of middle ear ossicles </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Other causes of conduction defects: impacted cerumen in outer ear canal; otitis media </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: amplification devices; surgery </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Conduction defect </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Weber test: lateralizes to affected ear </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rinne test: bone conduction > air conduction </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Otitis media (see <span>[[Fig. 25-41|Figure 25-41]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause of conduction deafness in children<br>Most commonly due to <i>Streptococcus pneumoniae</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Other causes: <i>Haemophilus influenzae</i>, <i>Moraxella catarrhalis</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: antipyrine and benzocaine ear drops for pain; controversy regarding antibiotics-those that use antibiotics usually use amoxicillin-clavulanate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> External otitis (see <span>[[Fig. 25-42|Figure 25-42]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inflammation of outer ear canal<br>"Swimmer's ear": due to <i>Pseudomonas aeruginosa</i>, <i>Staphylococcus aureus</i>, <i>Aspergillus</i> species </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: ear drops-polymyxin B + neomycin + hydrocortisone + selenium sulfide shampoo </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant external otitis: severe infection of outer ear canal in patients with diabetes mellitus; <i>Pseudomonas aeruginosa</i> most common cause </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: imipenem-cilastatin </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CELL TYPE</b></td><td align="LEFT" valign="BOTTOM"><b>DERIVATION</b></td><td align="LEFT" valign="BOTTOM"><b>LOCATION</b></td><td align="LEFT" valign="BOTTOM"><b>FUNCTION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> T cells<br> CD4 (helper)<br> CD8 (cytotoxic/suppressor) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bone marrow lymphocyte stem cells mature in thymus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral blood and bone marrow, thymus, paracortex of lymph nodes, Peyer's patches </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CD<sup>4</sup> cells: secrete cytokines (IL-2 → proliferation of CD<sup>4</sup>/CD8 T cells; IFN-γ → activation of macrophages); help B cells become antibody-producing plasma cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CD8 cells: kill virus-infected, neoplastic, and donor graft cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> B cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bone marrow stem cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral blood and bone marrow, germinal follicles in lymph nodes, Peyer's patches </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Differentiate into plasma cells that produce immunoglobulins to kill encapsulated bacteria (e.g., <i>Streptococcus pneumoniae</i>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Act as APCs that interact with CD<sup>4</sup> cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Natural killer cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bone marrow stem cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral blood (large granular lymphocytes) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Kill virus-infected and neoplastic cells<br>Release IFN-γ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macrophages </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Conversion of monocytes into macrophages in connective tissue </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Connective tissue; organs (e.g., alveolar macrophages, lymph node sinuses) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Involved in phagocytosis and cytokine production<br>Act as APCs to T cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dendritic cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bone marrow stem cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Skin (Langerhans' cells), germinal follicles </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Act as APCs to T cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> </td></tr></tbody></table><a name=""></a> <br>APC, antigen-presenting cell; IFN, interferon; IL, interleukin.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>REACTION</b></td><td align="LEFT" valign="BOTTOM"><b>PATHOGENESIS</b></td><td align="LEFT" valign="BOTTOM"><b>EXAMPLES</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type I </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IgE-dependent activation of mast cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Atopic disorders: hay fever, eczema, hives, asthma, reaction to bee sting<br>Drug hypersensitivity: penicillin rash or anaphylaxis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type II </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antibody-dependent reaction </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complement-dependent reactions </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lysis (IgM mediated): ABO mismatch, cold immune hemolytic anemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lysis (IgG mediated): Goodpasture's syndrome, PA </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Phagocytosis: warm (IgG) autoimmune hemolytic anemia, ABO and Rh hemolytic disease of newborn, ITP </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complement-independent reactions </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antibody (IgG)-dependent cell-mediated cytotoxicity: natural killer cell destruction of neoplastic and virus-infected cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antibody (IgE)-dependent cell-mediated cytotoxicity: eosinophil destruction of helminths </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antibodies directed against cell surface receptors: myasthenia gravis, Graves' disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type III </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Deposition of antigen-antibody complexes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Systemic lupus erythematosus (DNA-anti-DNA)<br>Serum sickness (horse antithymocyte globulin-antibody)<br>Poststreptococcal glomerulonephritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type IV </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antibody-independent T cell-mediated reactions </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Delayed type: tuberculous granuloma; PPD reaction, MS<br>Cell-mediated cytotoxicity: killing of tumor cells and virus-infected cells; contact dermatitis (e.g., poison ivy, nickel) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>ITP, idiopathic thrombocytopenic purpura; MS, multiple sclerosis; PA, pernicious anemia; PPD, purified protein derivative
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE OF TRANSPLANT</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cornea </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Best allograft survival rate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Danger of transmission of Creutzfeldt-Jakob disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Kidney </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Better survival with kidney from living donor than from cadaver </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bone marrow </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Graft contains pluripotential cells that repopulate host stem cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Host assumes donor ABO group </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Danger of graft-versus-host reaction and cytomegalovirus infection </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>AUTOANTIBODIES</b></td><td align="LEFT" valign="BOTTOM"><b>DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>TEST SENSITIVITY (%)</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-acetylcholine receptor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Myasthenia gravis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >85 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-basement membrane </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Goodpasture's syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >90 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anticentromere </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CREST syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 50-90 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antiendomysial IgA </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Celiac disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 95 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antigliadin IgA </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Celiac disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 80 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antihistone </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drug-induced lupus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 90-95 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-insulin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type 1 diabetes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 50 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-islet cell </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 75-80 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-intrinsic factor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pernicious anemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 60 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-parietal cell </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 90 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antimicrosomal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hashimoto's thyroiditis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 97 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-Smith (Sm) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Systemic lupus erythematosus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 30 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-SS-A (Ro) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sjögren's syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 70-95 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Systemic lupus erythematosus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 25-50 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-SS-B (La) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sjögren's syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 60-90 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antithyroglobulin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hashimoto's thyroiditis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 85 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-tissue transglutaminase IgA </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Celiac disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 98 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-topoisomerase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Systemic sclerosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 30 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antimitochondrial </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary biliary cirrhosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 90-100 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antimyeloperoxidase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Microscopic polyangiitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 80 (p-ANCA) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antinuclear </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Systemic lupus erythematosus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 99 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Systemic sclerosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 70-90 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dermatomyositis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <30 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antiproteinase 3 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wegener's granulomatosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >90 (c-ANCA) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-ribonucleoprotein </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> MCTD </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 85 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anti-TSH receptor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Graves' disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 85 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>c-ANCA, cytoplasmic antineutrophil cytoplasmic antibody; CREST, calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, telangiectasia; MCTD, mixed connective tissue disease; p-ANCA, perinuclear antineutrophilic cytoplasmic antibody.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISEASE</b></td><td align="LEFT" valign="BOTTOM"><b>DEFECT(S)</b></td><td align="LEFT" valign="BOTTOM"><b>CLINICAL FEATURES</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>B-Cell Disorders</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bruton's agammaglobulinemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Failure of pre-B cells to become mature B cells<br>Mutated tyrosine kinase<br>X-linked recessive disorder </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> SP infections<br>Maternal antibodies protective from birth to age 6 months<br>↓ Immunoglobulins </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IgA deficiency </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Failure of IgA B cells to mature into plasma cells </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> SP infections; giardiasis<br>Anaphylaxis if exposed to blood products that contain IgA<br>↓ IgA and secretory IgA </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common variable immunodeficiency </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Defect in B-cell maturation to plasma cells<br>Adult immunodeficiency disorder </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sinopulmonary infections (90-100%), GI infections (e.g., <i>Giardia</i>), pneumonia, autoimmune disease (ITP, AIHA), malignancy (25%) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common pathogens: <i>Actinomyces israeli</i>, <i>Streptococcus pneumoniae</i>, <i>Haemophilus influenzae</i>; chronic infections-<i>Staphylococcus aureus, Pseudomonas aeruginosa</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ Immunoglobulins </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>T-Cell Disorder</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> DiGeorge syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Failure of third and fourth pharyngeal pouches to develop </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypoparathyroidism (tetany); absent thymic shadow on radiograph; PCP </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thymus and parathyroid glands fail to develop </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Danger of GVH reaction </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>Combined B- and T-Cell Disorders</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Severe combined immunodeficiency (SCID) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenosine deaminase deficiency (15%); autosomal recessive disorder; adenine toxic to B and T cells; ↓ deoxynucleoide triphosphate precursors for DNA synthesis<br>Other disorders: stem cell defect </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Defective CMI<br>↓ Immunoglobulins<br>Treatment: gene therapy, bone marrow transplant (patients with SCID do <i>not</i> reject allografts) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wiskott-Aldrich syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Progressive deletion of B and T cells<br>X-linked recessive disorder </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Symptom triad: eczema, thrombocytopenia, SP infections<br>Associated risk of malignant lymphoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Defective CMI </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ IgM, normal IgG, ↑ IgA and IgE </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ataxia-telangiectasia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mutation in DNA repair enzymes<br>Thymic hypoplasia<br>Autosomal recessive disorder </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cerebellar ataxia, telangiectasias of eyes and skin<br>↑ Risk of lymphoma and/or leukemia; adenocarcinoma<br>↑ Serum α-fetoprotein<br>↓ IgA 50-80%, ↓ IgE, IgM low molecular weight variety, ↓ IgG2 or total IgG; ↓ T cell function </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>AIHA, autoimmune hemolytic anemia; CMI, cell-mediated immunity; GI, gastrointestinal; GVH, graft-versus-host; ITP, idiopathic thrombocytopenic purpura; PCP, <i>Pneumocystis jiroveci</i> pneumonia; SP, sinopulmonary.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TEST</b></td><td align="LEFT" valign="BOTTOM"><b>USE</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ELISA </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Screening test </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Detects anti-gp120 antibodies </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sensitivity ∼ 100% </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Positive within 3-5 weeks; all in 3 months </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Western blot </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Confirmatory test </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Used if ELISA is positive or indeterminate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Positive test: presence of p24 antigen and gp41 antibodies and either gp120 or gp160 antibodies </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Specificity ∼ 100% </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> p24 antigen </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Indicator of active viral replication<br>Present before anti-gp120 antibodies </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Positive prior to seroconversion and when AIDS is diagnosed (two distinct peaks) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CD4 T-cell count </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Monitoring immune status </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Useful in determining when to initiate HIV treatment and when to administer prophylaxis against opportunistic infections </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HIV viral load </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Detection of actively dividing virus<br>Marker of disease progression </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most sensitive test for diagnosis of acute HIV before seroconversion </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>AIDS, acquired immunodeficiency syndrome; ELISA, enzyme-linked immunosorbent assay; HIV, human immunodeficiency virus.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hereditary angioedema </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal dominant disorder with deficiency of C1 esterase inhibitor </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Continued C1 activation decreases C2 and C4 and increases their cleavage products, which have anaphylatoxic activity </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal C3 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Swelling of face and oropharynx </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> C2 deficiency </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common complement deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Association with septicemia (usually <i>Streptococcus pneumoniae</i>) and lupus-like syndrome in children </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> C6-C9 deficiency </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased susceptibility to disseminated <i>Neisseria gonorrhoeae</i> or <i>N. meningitidis</i> infections </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Paroxysmal nocturnal hemoglobinuria </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acquired stem cell disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Defect in molecule anchoring decay accelerating factor (DAF), which normally degrades C3 and C5 convertase on hematopoietic cell membranes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complement-mediated intravascular lysis of red blood cells (hemoglobinuria), platelets, and neutrophils </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE OF AMYLOIDOSIS</b></td><td align="LEFT" valign="BOTTOM"><b>CLINICAL FINDINGS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary and secondary </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nephrotic syndrome, renal failure (common cause of death) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Arrhythmia, heart failure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macroglossia, malabsorption </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatosplenomegaly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Carpal tunnel syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Senile cerebral </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dementia (Alzheimer's type) caused by toxic Aβ deposits in neurons </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Amyloid precursor protein coded by chromosome 21 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with Down syndrome </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>COMPARTMENT ALTERATION</b></td><td align="LEFT" valign="BOTTOM"><b>POsm/Na<sup>+</sup></b></td><td align="LEFT" valign="BOTTOM"><b>ECF VOLUME</b></td><td align="LEFT" valign="BOTTOM"><b>ICF VOLUME</b></td><td align="LEFT" valign="BOTTOM"><b>CONDITIONS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal ECF and ICF volume<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g001.jpg" id=""> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal hydration </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Isotonic net loss Na<sup>+</sup> + H<sub>2</sub>O<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g002.jpg" id=""> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal<br>↓TBNa<sup>+</sup>/↓TBW </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adult diarrhea<br>Loss whole blood </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Isotonic net gain Na<sup>+</sup> + H<sub>2</sub>O<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g003.jpg" id=""> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal<br>↑ TBNa<sup>+</sup>/↑ TBW </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Expanded </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Excessive isotonic saline </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Net loss Na<sup>+</sup> in excess of H<sub>2</sub>O<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g004.jpg" id=""> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased<br>↓↓TBNa<sup>+</sup>/↓TBW </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Expanded </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loop diuretics<br>Addison's disease<br>21-Hydroxylase deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Net gain in only water<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g005.jpg" id=""> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased<br>TBNa<sup>+</sup>/↑↑ TBW </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Expanded </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Expanded </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> SIADH<br>Compulsive water drinker </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Net gain in H<sub>2</sub>O in excess of Na<sup>+</sup><br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g006.jpg" id=""> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased<br>↑ TBNa<sup>+</sup>/↑↑ TBW </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Expanded<br>Starling pressure alteration </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Expanded </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Right-sided heart failure<br>Cirrhosis<br>Nephrotic syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> </td></tr></tbody></table><a name=""></a> <br>ECF, extracellular fluid; ICF, intracellular fluid; POsm, plasma osmolality; SIADH, syndrome of inappropriate antidiuretic hormone; TB total body; TBW total body water.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>pH</b></td><td align="LEFT" valign="BOTTOM"><b>Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> (mm HG)</b></td><td align="LEFT" valign="BOTTOM"><b>HCO<sub>3</sub><sup>-</sup> (mEq/L)</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.35-7.45 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 33-45 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 22-28 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal ranges </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.00 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 52 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 13 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mixed disorder (extreme acidemia): primary metabolic acidosis (HCO<sub>3</sub><sup>-</sup>< 22 mEq/L), primary respiratory acidosis (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Example</i>: cardiorespiratory arrest </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.20 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 74 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 28 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute respiratory acidosis, uncompensated (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg, HCO<sub>3</sub><sup>-</sup> < 30 mEq/L) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Example</i>: CNS respiratory center depression (e.g., barbiturate poisoning) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.33 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 60 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 31 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic respiratory acidosis with partially compensated metabolic alkalosis (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg, HCO<sub>3</sub><sup>-</sup> > 30 mEq/L) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Examples</i>: chronic bronchitis, cystic fibrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.28 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 28 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 12 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metabolic acidosis with partially compensated respiratory alkalosis (HCO<sub>3</sub><sup>-</sup> < 22 mEq/L, Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> < 33 mm Hg) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Examples</i>: disorders associated with increased and normal anion gap metabolic acidosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.42 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 22 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 14 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mixed disorder (normal pH): primary metabolic acidosis (HCO<sub>3</sub><sup>-</sup> < 22 mEq/L), primary respiratory alkalosis (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> < 33 mm Hg) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Examples</i>: salicylate poisoning, septic shock </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.50 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 47 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 35 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metabolic alkalosis with partially compensated respiratory acidosis (HCO<sub>3</sub><sup>-</sup> > 28 mEq/L, Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Causes</i>: loop/thiazide diuretics, vomiting, mineralocorticoid excess </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.56 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 24 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 21 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute respiratory alkalosis with partially compensated metabolic acidosis (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> < 33 mm Hg, HCO<sub>3</sub><sup>-</sup> < 22 mEq/L) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Causes</i>: anxiety, pulmonary embolus, normal pregnancy </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE OF SHOCK</b></td><td align="LEFT" valign="BOTTOM"><b>CO</b></td><td align="LEFT" valign="BOTTOM"><b>PVR</b></td><td align="LEFT" valign="BOTTOM"><b>LVEDP</b></td><td align="LEFT" valign="BOTTOM"><b>MVO<sub>2</sub></b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypovolemic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cardiogenic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Endotoxic (septic) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↓ </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ↑ </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> </td></tr></tbody></table><a name=""></a> <br>CO, cardiac output; LVEDP, left ventricular end-diastolic pressure; MVO<sub>2</sub>, mixed venous oxygen content; PVR, peripheral vascular resistance.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>COMPARTMENT ALTERATION</b></td><td align="LEFT" valign="BOTTOM"><b>POsm/Na<sup>+</sup></b></td><td align="LEFT" valign="BOTTOM"><b>ECF VOLUME</b></td><td align="LEFT" valign="BOTTOM"><b>ICF VOLUME</b></td><td align="LEFT" valign="BOTTOM"><b>CONDITIONS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Net loss of H<sub>2</sub>O in excess of Na<sup>+</sup><br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g007.jpg" id=""> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased<br>↓TBNa<sup>+</sup>/↓↓TBW </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osmotic diuresis: glucose<br>Sweating </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Net loss of only water<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g008.jpg" id=""> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased<br>TBNa<sup>+</sup>/↓↓TBW </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted (mild) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insensible water loss: fever<br>Diabetes insipidus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Net gain in Na+ in excess of H<sub>2</sub>O<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g009.jpg" id=""> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased<br>↑↑ TBNa<sup>+</sup>/↑ TBW </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Expanded </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infusion of a Na<sup>+</sup>-containing antibiotic<br>Infusion of NaHCO<sub>3</sub> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hyperglycemia<br><br><img valign="absmiddle" border="0" src="9780323068628/Images_9780323068628/M9780323068628-004-g010.jpg" id=""> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased<br>↑ Glucose<br>↓ Na<sup>+</sup> (dilutional effect) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Contracted </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diabetic ketoacidosis<br>Hyperosmolar nonketotic coma (type 2 diabetes) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> </td></tr></tbody></table><a name=""></a> <br>ECF, extracellular fluid; ICF, intracellular fluid; POsm, plasma osmolality; TB, total body; TBW total body water.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>PATHOGENESIS</b></td><td align="LEFT" valign="BOTTOM"><b>CAUSES</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased intake </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs in elderly patients, those with eating disorders </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transcellular shift (intracellular) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alkalosis (intracellular shift of K<sup>+</sup>)<br>Drugs enhancing Na<sup>+</sup>/K<sup>+</sup>-ATPase pump: insulin, β<sub>2</sub>-agonists (e.g., albuterol) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastrointestinal loss </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diarrhea (∼30 mEq/L in stool) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Laxatives </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vomiting (∼5 mEq/L in gastric juice) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal loss </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loop and thiazide diuretics (most common cause): excessive exchange of Na<sup>+</sup> for K<sup>+</sup> in late distal and collecting tubules </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osmotic diuresis: glucosuria </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mineralocorticoid excess: primary aldosteronism, 11-hydroxylase deficiency, Cushing syndrome (excessive exchange of Na<sup>+</sup> for K<sup>+</sup> in late distal and collecting tubules), glycyrrhizic acid (licorice, chewing tobacco), secondary aldosteronism (cirrhosis, congestive heart failure, nephrotic syndrome; decreased cardiac output decreases blood flow and activates renin-angiotensin-aldosterone system) </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>PATHOGENESIS</b></td><td align="LEFT" valign="BOTTOM"><b>CAUSES</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tissue breakdown </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Iatrogenic (e.g., venipuncture); pseudohyperkalemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rhabdomyolysis (rupture of muscle) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased intake </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased intake of salt substitute </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infusion of old blood </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> K<sup>+</sup>-containing antibiotics </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transcellular shift (extracellular) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acidosis<br>Drugs inhibiting Na<sup>+</sup>/K<sup>+</sup>-ATPase pump: β-blocker (e.g., propranolol), digitalis toxicity, succinylcholine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased renal excretion </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal disease: renal failure (most common cause), interstitial nephritis (legionnaires' disease; lead poisoning) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mineralocorticoid deficiency: Addison's disease, 21-hydroxylase deficiency, hyporeninemic hypoaldosteronism (destruction of juxtaglomerular apparatus) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drugs: spironolactone (inhibits aldosterone); triamterene, amiloride (inhibit Na<sup>+</sup> channels) </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>ANATOMIC SITE</b></td><td align="LEFT" valign="BOTTOM"><b>RESPIRATORY ACIDOSIS</b></td><td align="LEFT" valign="BOTTOM"><b>RESPIRATORY ALKALOSIS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CNS respiratory center </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Depression of center: trauma, barbiturates </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Overstimulation: anxiety, high altitude, normal pregnancy (estrogen/progesterone effect), salicylate poisoning, endotoxic (septic) shock, cirrhosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Upper airway </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Obstruction: acute epiglottitis (<i>Haemophilus influenzae</i>), croup (parainfluenza virus) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Muscles respiration </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Paralysis: ALS, phrenic nerve injury, Guillain-Barré syndrome, poliomyelitis, hypokalemia, hypophosphatemia (↓ ATP) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rib fracture: hyperventilation from pain </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lungs </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Obstructive disease: chronic bronchitis, cystic fibrosis<br>Other: pulmonary edema, ARDS, RDS, severe bronchial asthma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Restrictive disease: sarcoidosis, asbestosis<br>Others: pulmonary embolus, mild bronchial asthma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>ALS, amyotrophic lateral sclerosis; ARDS, acute respiratory distress syndrome; ATP, adenosine triphosphate; RDS, respiratory distress syndrome.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CAUSES</b></td><td align="LEFT" valign="BOTTOM"><b>PATHOGENESIS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lactic acidosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common type </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Any cause of tissue hypoxia with concomitant anaerobic glycolysis: e.g., shock, CN poisoning, CO poisoning, severe hypoxemia (Pao<sub>2</sub> < 35 mm Hg), CHF, severe anemia (Hb < 6 g/dL) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alcoholism: pyruvate is converted to lactate from the excess of NADH in alcohol metabolism. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Liver disease: liver normally converts lactate to pyruvate. Liver disease (e.g., hepatitis, cirrhosis) causes lactate to accumulate in the blood. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drugs: e.g., phenformin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ketoacidosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diabetic ketoacidosis (type 1 diabetes mellitus): accumulation of AcAc and β-OHB </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alcoholism: acetyl CoA in alcohol metabolism is converted to ketoacids. Increase in NADH causes AcAc to convert to β-OHB, which is <i>not</i> detected with standard tests for ketone bodies. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Starvation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal failure </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Retention of organic acids: e.g., sulfuric and phosphoric acids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Salicylate poisoning </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Salicylic acid is an acid. It is also a mitochondrial toxin that uncouples oxidative phosphorylation leading to tissue hypoxia and lactic acidosis. In some cases, excess salicylate overstimulates the CNS respiratory center producing a primary respiratory alkalosis. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ethylene glycol poisoning </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ethylene glycol is in antifreeze. It is converted to glycolic and oxalic acid by alcohol dehydrogenase. Oxalate anions combine with calcium to produce calcium oxalate crystals that obstruct the renal tubules causing renal failure. IV infusion of ethanol decreases the metabolism of ethylene glycol, because alcohol dehydrogenase is preferentially metabolizing alcohol. Unmetabolized ethylene glycol is removed by hemodialysis. Another treatment is the use of 4-methylpyrazole, which inhibits alcohol dehydrogenase. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osmolal gap > 10 mOsm/kg. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Methyl alcohol poisoning </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Methyl alcohol is present in windshield washer fluid, Sterno, and solvents for paints. It is converted into formic acid by alcohol dehydrogenase. Formic acid damages the optic nerve causing optic neuritis and the potential for permanent blindness. IV infusion of ethanol decreases the metabolism of methyl alcohol, because alcohol dehydrogenase is preferentially metabolizing alcohol. Another treatment is the use of 4-methylpyrazole, which inhibits alcohol dehydrogenase. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osmolal gap > 10 mOsm/kg. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>AcAc, acetoacetate; β-OHB, β-hydroxybutyrate; CHF, congestive heart failure; CN, cyanide; CO, carbon monoxide; Hb, hemoglobin; IV, intravenous; NADH, reduced form of nicotinamide adenine dinucleotide.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CAUSE</b></td><td align="LEFT" valign="BOTTOM"><b>PATHOGENESIS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diarrhea </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common cause in children </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of HCO<sub>3</sub><sup>-</sup> in stool: HCO<sub>3</sub><sup>-</sup> is secreted from the pancreas to alkalinize the gastric meal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cholestyramine </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Binds HCO<sub>3</sub><sup>-</sup> as well as bile salts, vitamins, and some drugs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drainage of bile or pancreatic secretions </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bile and pancreatic secretions contain large amounts of HCO<sub>3</sub><sup>-</sup> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type I distal renal tubular acidosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inability to regenerate HCO<sub>3</sub><sup>-</sup> in the H<sup>+</sup>/K<sup>+</sup>-ATPase pump in the collecting tubules. Excess H<sup>+</sup> ions in the blood combine with Cl<sup>-</sup> anions. Hypokalemia is severe. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inability to secrete H<sup>+</sup> ions decreases titratable acidity and NH<sub>4</sub>Cl causing the urine pH to be > 5.5. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: amphotericin, light chains in multiple myeloma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rx: oral administration of HCO<sub>3</sub><sup>-</sup> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type II proximal renal tubular acidosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal threshold for reclaiming HCO<sub>3</sub><sup>-</sup> is lowered from a normal of ∼ 24 mEq/L to ∼ 15 mEq/L </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urine pH is initially > 5.5 due to loss of filtered HCO<sub>3</sub><sup>-</sup> in the urine. When the serum HCO<sub>3</sub><sup>-</sup> is equal to the renal threshold, the proximal tubules reclaim HCO<sub>3</sub><sup>-</sup> causing the urine pH to drop to < 5.5. Hypokalemia may occur due to K<sup>+</sup> binding to HCO<sub>3</sub><sup>-</sup>. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: carbonic anhydrase inhibitors (most common cause), primary hyperparathyroidism (PTH, ↓ proximal tubule HCO<sub>3</sub><sup>-</sup> reclamation), proximal tubule nephrotoxic drugs/chemicals (e.g., aminoglycosides, heavy metals). </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rx: thiazides to produce volume depletion, which increases the renal threshold for reclaiming HCO<sub>3</sub><sup>-</sup> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type IV renal tubular acidosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Due to destruction of the JG apparatus: e.g., hyaline arteriolosclerosis of afferent arterioles in DM, acute or chronic tubulointerstitial inflammation (e.g., legionnaires' disease) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces hyporeninemic hypoaldosteronism </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Only RTA with hyperkalemia: due to hypoaldosteronism </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>DM, diabetes mellitus; JG, juxtaglomerular; PTH, parathyroid hormone; RTA, renal tubular acidosis; Rx, treatment.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CAUSE</b></td><td align="LEFT" valign="BOTTOM"><b>PATHOGENESIS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vomiting </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of hydrochloric acid. For every H<sup>+</sup> ion lost in the vomitus there is a corresponding HCO<sub>3</sub><sup>-</sup> in the blood. This causes metabolic alkalosis; however, it is filtered by the kidney and must be reclaimed in order to maintain the increase in serum HCO<sub>3</sub><sup>-</sup>. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Volume depletion from excessive vomiting increases proximal tubule reclamation of HCO<sub>3</sub><sup>-</sup> (renal threshold for reclaiming HCO<sub>3</sub><sup>-</sup> is increased). </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Correction of volume depletion with 0.9% normal saline corrects the alkalosis (chloride-responsive), because the renal threshold returns to normal and the excess filtered HCO<sub>3</sub><sup>-</sup> is lost in the urine. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mineralocorticoid excess </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gain in HCO<sub>3</sub><sup>-</sup> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Enhanced function of aldosterone-mediated Na<sup>+</sup>-H<sup>+</sup> channels in the late distal and collecting ducts increases the synthesis of HCO<sub>3</sub><sup>-</sup> leading to metabolic alkalosis (see <span>[[Fig. 4-8|Figure 4-8]]</span>); infusion of 0.9% normal saline does <i>not</i> correct the metabolic alkalosis (chloride-resistant). </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Causes: primary aldosteronism, 11-hydroxylase deficiency, Cushing syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thiazide and loop diuretics </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gain in HCO<sub>3</sub><sup>-</sup> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Block in Na<sup>+</sup> reabsorption leads to augmented late distal and collecting tubule reabsorption of Na<sup>+</sup> and excretion of H<sup>+</sup>, the latter increasing synthesis of HCO<sub>3</sub><sup>-</sup>, leading to metabolic alkalosis (see <span>[[Fig. 4-8|Figure 4-8]]</span>); volume depletion also increases the proximal tubule reclamation of HCO<sub>3</sub><sup>-</sup>, which maintains the metabolic alkalosis. </td></tr></tbody></table><a name=""></a>
</html>
<html>
Table 4-10.
SELECTED ARTERIAL BLOOD GAS PROFILES<table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>SERUM NA<sup>+</sup> (mEq/L)</b></td><td align="LEFT" valign="BOTTOM"><b>SERUM K<sup>+</sup> (mEq/L)</b></td><td align="LEFT" valign="BOTTOM"><b>SERUM Cl<sup>-</sup> (mEq/L)</b></td><td align="LEFT" valign="BOTTOM"><b>SERUM HCO<sub>3</sub><sup>-</sup> (mEq/L)</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 136-145 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 3.5-5.0 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 95-105 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 22-28 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal ranges </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 118 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 3.0 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 84 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 22 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> SIADH: dilutional effect of excess water on all electrolytes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 128 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 5.9 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 96 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 20 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Addison's disease: lack of aldosterone causes loss of Na<sup>+</sup> (hyponatremia), retention of K<sup>+</sup> (hyperkalemia), and decreased synthesis of HCO<sub>3</sub><sup>-</sup> (metabolic acidosis; see <span>[[Fig. 4-8|Figure 4-8]]</span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 130 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 2.9 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 80 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 36 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vomiting: loss of Na<sup>+</sup> and K<sup>+</sup> in vomitus (hyponatremia, hypokalemia); volume depletion causes increased reclamation of HCO<sub>3</sub><sup>-</sup> in proximal tubule (metabolic alkalosis; see <span>[[Fig. 4-5|Figure 4-5]]</span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loop and thiazide diuretics: hypertonic loss Na<sup>+</sup> in urine (hypernatremia); augmented exchange of Na<sup>+</sup> for K<sup>+</sup> (hypokalemia) and increased regeneration of HCO<sub>3</sub><sup>-</sup> (metabolic alkalosis, see <span>[[Fig. 4-8|Figure 4-8]]</span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 152 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 2.8 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 110 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 33 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mineralocorticoid excess: primary aldosteronism; augmented exchange of Na<sup>+</sup> for K<sup>+</sup> (hypernatremia, hypokalemia), and increased synthesis of HCO<sub>3</sub><sup>-</sup> (metabolic alkalosis, see <span>[[Fig. 4-8|Figure 4-8]]</span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="5"> </td></tr><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>pH</b></td><td align="LEFT" valign="BOTTOM"><b>Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> (mm HG)</b></td><td align="LEFT" valign="BOTTOM"><b>HCO<sub>3</sub><sup>-</sup> (mEq/L)</b></td><td align="LEFT" valign="BOTTOM"><b>DISCUSSION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.35-7.45 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 33-45 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 22-28 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal ranges </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.00 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 52 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 13 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mixed disorder (extreme acidemia): primary metabolic acidosis (HCO<sub>3</sub><sup>-</sup>< 22 mEq/L), primary respiratory acidosis (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Example</i>: cardiorespiratory arrest </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.20 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 74 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 28 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute respiratory acidosis, uncompensated (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg, HCO<sub>3</sub><sup>-</sup> < 30 mEq/L) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Example</i>: CNS respiratory center depression (e.g., barbiturate poisoning) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.33 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 60 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 31 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic respiratory acidosis with partially compensated metabolic alkalosis (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg, HCO<sub>3</sub><sup>-</sup> > 30 mEq/L) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Examples</i>: chronic bronchitis, cystic fibrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.28 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 28 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 12 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metabolic acidosis with partially compensated respiratory alkalosis (HCO<sub>3</sub><sup>-</sup> < 22 mEq/L, Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> < 33 mm Hg) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Examples</i>: disorders associated with increased and normal anion gap metabolic acidosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.42 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 22 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 14 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mixed disorder (normal pH): primary metabolic acidosis (HCO<sub>3</sub><sup>-</sup> < 22 mEq/L), primary respiratory alkalosis (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> < 33 mm Hg) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Examples</i>: salicylate poisoning, septic shock </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.50 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 47 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 35 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metabolic alkalosis with partially compensated respiratory acidosis (HCO<sub>3</sub><sup>-</sup> > 28 mEq/L, Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> > 45 mm Hg) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Causes</i>: loop/thiazide diuretics, vomiting, mineralocorticoid excess </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 7.56 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 24 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 21 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute respiratory alkalosis with partially compensated metabolic acidosis (Pa<span style="font-variant:small-caps;">co</span><sub>2</sub> < 33 mm Hg, HCO<sub>3</sub><sup>-</sup> < 22 mEq/L) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Causes</i>: anxiety, pulmonary embolus, normal pregnancy </td></tr></tbody></table><a name=""></a> <br>SIADH, syndrome of inappropriate antidiuretic hormone.
<a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>PROTEIN TYPE</b></td><td align="LEFT" valign="BOTTOM"><b>SPECIFIC PROTEIN</b></td><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>INHERITANCE PATTERN</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Enzyme </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> C1 esterase inhibitor deficiency<br>Glucose-6-phosphate dehydrogenase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hereditary angioedema<br>Glucose-6-phosphate dehydrogenase deficiency </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal dominant<br>X-linked recessive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Structural </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sickle hemoglobin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sickle cell disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal recessive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ankyrin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hereditary spherocytosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal dominant </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dystrophin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Duchenne's muscular dystrophy </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> X-linked recessive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transport </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cystic fibrosis transmembrane regulator </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cystic fibrosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal recessive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Receptor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Low-density lipoprotein receptor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Familial hypercholesterolemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal dominant </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Growth regulating </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neurofibromin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neurofibromatosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal dominant </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemostasis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Factor VIII </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemophilia A </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> X-linked recessive </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>DEFICIENT ENZYME</b></td><td align="LEFT" valign="BOTTOM"><b>ACCUMULATED SUBSTRATE</b></td><td align="LEFT" valign="BOTTOM"><b>CLINICAL FINDINGS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gaucher's disease (adult type) (see <span>[[Fig. 13-14|Figure 13-14]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glucocerebrosidase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glucocerebroside </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatosplenomegaly; fibrillar-appearing macrophages in liver, spleen, and bone marrow </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hurler's syndrome (see <span>[[Fig. 5-9|Figure 5-9]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> α-<span style="font-variant:small-caps;">l</span>-Iduronidase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dermatan and heparan sulfate </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mental retardation, coarse facial features, short neck, corneal clouding, coronary artery disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> X-linked recessive form (Hunter's syndrome) is milder </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Niemann-Pick disease (see <span>[[Fig. 13-15|Figure 13-15]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sphingomyelinase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sphingomyelin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mental retardation, hepatosplenomegaly, foamy macrophages </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tay-Sachs disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hexosaminidase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> GM<sub>2</sub> ganglioside </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mental retardation, muscle weakness, cherry-red macula, blindness </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TERATOGEN</b></td><td align="LEFT" valign="BOTTOM"><b>DEFECT</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alcohol (see <span>[[Fig. 5-21|Figure 5-21]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mental retardation (leading cause in Western Hemisphere), microcephaly, VSD, ASD, attention deficit, diagnostic facial features (thinning of upper lip, flattening of grove between nose and upper lip, small eye openings) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cocaine </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Microcephaly, low birth weight, renal agenesis, congenital heart disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> DES </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vaginal and/or cervical clear cell carcinoma, müllerian defects </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Phenytoin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nail and distal phalanx hypoplasia, cleft lip and/or palate, neuroblastoma, bleeding (vitamin K deficiency) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Isotretinoin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hearing defects, missing ear lobes, visual impairment, facial dysmorphism, mental retardation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thalidomide </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Amelia (absent limbs), phocomelia (seal-like limbs), deafness </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tobacco </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IUGR, low birth weight </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Valproate </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neural tube defects (valproate is a folate antagonist), autism </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Warfarin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nasal hypoplasia, agenesis corpus callosum, fetal bleeding and death </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>ASD, atrial septal defect; DES, diethylstilbestrol; IUGR, intrauterine growth retardation; VSD, ventricular septal defect.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>INFECTION</b></td><td align="LEFT" valign="BOTTOM"><b>TRANSMISSION</b></td><td align="LEFT" valign="BOTTOM"><b>CLINICAL FINDINGS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cytomegalovirus (see <span>[[Fig. 25-24A|Figure 25-24]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transplacental </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Deafness, IUGR, CNS calcification (periventricular)<br>Culture urine (best fluid to culture), urine cytologic findings: intranuclear inclusions </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Herpes simplex type 2 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Birth canal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> IUGR, vesicular lesions or scarring, keratoconjunctivitis, microcephaly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rubella </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transplacental </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Deafness (sensorineural), PDA, cataract, thrombocytopenia ("blueberry muffin" rash), hepatomegaly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Syphilis (see <span>[[Fig. 17-2E|Figure 17-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transplacental </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Occurs after 20 weeks' gestation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatitis, saddle nose, blindness, peg teeth </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Toxoplasmosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transplacental </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Blindness (chorioretinitis), deafness (sensorineural), CNS calcification (basal ganglia), IUGR, hydrocephalus, hepatosplenomegaly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pregnant woman should avoid cat litter, raw meat </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Varicella </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transplacental </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Limb defects, mental retardation, blindness (chorioretinitis), cataracts, skin scars </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HIV </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transplacental, birth canal, breast feeding </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oral thrush, recurrent bacterial infections, intracranial calcification, failure to thrive </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>IUGR, intrauterine growth retardation; PDA, patent ductus arteriosus.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>SYSTEM</b></td><td align="LEFT" valign="BOTTOM"><b>DESCRIPTION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Auditory </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Presbycusis: sensorineural hearing loss, particularly at high frequency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Otosclerosis: fusion of ear ossicles producing conductive hearing loss </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cardiovascular </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loss of elasticity in aorta (increases systolic pressure) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Central nervous </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cerebral atrophy with mild forgetfulness </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Impaired sleep patterns such as insomnia, early wakening </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased dopaminergic synthesis: parkinsonian-like gait </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Female reproductive </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Breast and vulvar atrophy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased estrogen and progesterone: FSH and LH, respectively </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastrointestinal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased gastric acidity: predisposes to <i>Helicobacter pylori</i> infection </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased colonic motility: constipation predisposing to diverticulosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> General </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased body fat: decreased number insulin receptors (glucose intolerance) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Immune </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased skin response to antigens (called anergy) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Male reproductive </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prostate hyperplasia: predisposes to urinary retention </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prostate cancer </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Musculoskeletal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osteoarthritis in weight-bearing joints </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased GFR: increased risk of drug toxicity from slow clearance of drugs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Respiratory </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mild obstructive pattern in pulmonary function tests: e.g., increased TLC </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mild hypoxemia and increased A-a gradient </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Skin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased skin elasticity due to increased cross-bridging of collagen </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Senile purpura over the dorsum of the hands and lower legs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Visual </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cataracts: visual impairment, increased risk for falls </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Presbyopia: inability to focus on near objects </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br><span style="font-variant:small-caps;">a</span>-a, alveolar-arterial; FSH, follicle-stimulating hormone; GFR, glomerular filtration rate; LH, luteinizing hormone; TLC, total lung capacity.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>SYSTEM</b></td><td align="LEFT" valign="BOTTOM"><b>DESCRIPTION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cardiovascular </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Atherosclerosis: increased risk for coronary artery disease, peripheral vascular disease, strokes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aortic stenosis: most common valvular abnormality in the elderly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Systolic hypertension: due to loss of aortic elasticity </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Central nervous </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alzheimer's disease: most common cause of dementia in people older than 65 years </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Parkinson's disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Subdural hematomas: due to falls </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Endocrine </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type 2 diabetes mellitus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Female reproductive </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased incidence of cancers of the breast, endometrium, ovary </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastrointestinal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased incidence of colorectal cancer </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Immune </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> MGUS: most common cause of monoclonal gammopathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Musculoskeletal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osteoporosis: vertebral column in females and femoral head in males </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal/lower urinary tract </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renovascular hypertension secondary to atherosclerosis<br>Urinary incontinence </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Respiratory </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pneumonia: usually <i>Streptococcus pneumoniae</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary lung cancer: particularly in smokers </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Skin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> UVB-induced cancers: e.g., basal cell carcinoma (most common) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Actinic (solar) keratosis: precursor for squamous cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pressure sores: pressure on capillaries is the most important risk factor </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Visual </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macular degeneration: most common cause of blindness in the elderly </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>MGUS, monoclonal gammopathy of undetermined significance; UVB, ultraviolet light B.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>SYSTEM</b></td><td align="LEFT" valign="BOTTOM"><b>EFFECTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cardiovascular </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> AMI </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sudden cardiac death </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral vascular disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypertension </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Central nervous </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Strokes: intracerebral bleeding, subarachnoid hemorrhage </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastrointestinal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for oropharyngeal cancer: squamous cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for upper, midesophageal cancer: squamous cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for stomach cancer: adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastroesophageal reflux disease: decreases tone of LES </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Delayed healing of peptic ulcers </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for pancreatic cancer: adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> General </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Low birth weight in newborns, IUGR </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neutrophilic leukocytosis: decreased activation of neutrophil adhesion molecules </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased concentration of ascorbic acid (used up in neutralizing hydroxyl free radicals) and β-carotenes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Genitourinary </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for cervical cancer: squamous cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ? Decreased free testosterone in males (↑ sex-hormone binding globulin) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased estrogen in females (early menopause) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for kidney cancer: renal cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for urinary bladder cancer: transitional cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hematologic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for acute myelogenous leukemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Integument </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased facial wrinkling </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Musculoskeletal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osteoporosis: due to decreased estrogen in females and decreased free testosterone in males </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Respiratory </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for laryngeal cancer: squamous cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic obstructive pulmonary disease: chronic bronchitis, emphysema </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for lung cancer: squamous cell carcinoma, small cell carcinoma, some types of adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Special senses </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased sense of smell and taste </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Blindness: macular degeneration </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cataracts </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>AMI, acute myocardial infarction; IUGR, intrauterine growth retardation; LES, lower esophageal sphincter.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>SYSTEM</b></td><td align="LEFT" valign="BOTTOM"><b>EFFECTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cardiovascular </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dilated cardiomyopathy: due to thiamine deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypertension: vasopressor effects due to increase in catecholamines </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Central nervous system </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CNS depressant: particularly cerebral cortex and limbic system </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wernicke's syndrome: confusion, ataxia, nystagmus due to thiamine deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Korsakoff's psychosis: memory deficits due to thiamine deficiency </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cerebellar atrophy: due to loss of Purkinje cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cerebral atrophy: due to loss of neurons </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Central pontine myelinolysis: due to rapid intravenous fluid correction of hyponatremia in an alcoholic </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gastrointestinal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oropharyngeal and upper to midesophageal cancer: squamous cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute hemorrhagic gastritis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mallory-Weiss syndrome: tear of distal esophagus due to retching </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Boerhaave's syndrome: rupture of distal esophagus due to retching </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Esophageal varices: caused by portal vein hypertension in alcoholic cirrhosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute and chronic pancreatitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> General </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fetal alcohol syndrome: mental retardation, microcephaly, atrial septal and ventricular septal defects </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Genitourinary </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Testicular atrophy: decreased testosterone, decreased spermatogenesis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased risk for spontaneous abortion </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hematopoietic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Folate deficiency: decreased reabsorption in jejunum; macrocytic anemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acquired sideroblastic anemia: microcytic anemia due to defect in heme synthesis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Anemia chronic disease: most common anemia in alcoholics </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatobiliary </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fatty liver, alcoholic hepatitis, cirrhosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatocellular carcinoma: preexisting cirrhosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Integument </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Porphyria cutanea tarda: photosensitive bullous skin lesions </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Musculoskeletal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rhabdomyolysis: direct alcohol effect on muscle </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral nervous system </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Peripheral neuropathy: due to thiamine deficiency </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DRUG</b></td><td align="LEFT" valign="BOTTOM"><b>DESCRIPTION</b></td><td align="LEFT" valign="BOTTOM"><b>TOXIC EFFECTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cocaine </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Stimulant </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mydriasis, tachycardia, hypertension </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated risk of AMI, CNS infarction, perforation of nasal septum (intranasal use) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Heroin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Opiate </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Miotic pupils, noncardiogenic pulmonary edema (frothing from mouth), focal segmental glomerulosclerosis (nephrotic syndrome) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Granulomatous reactions in skin and lungs from material used to "cut" (dilute) drug </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Marijuana <i>(Cannabis)</i>* </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> THC-containing psychoactive stimulant </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Red conjunctivae, euphoria, delayed reaction time </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> MPTP </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> By-product of synthesis of meperidine </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Irreversible Parkinson's disease: cytotoxic to neurons in nigrostriatal dopaminergic pathways </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>*Used medically to decrease nausea and vomiting associated with chemotherapy and to decrease intraocular pressure in glaucoma.<br>AMI, myocardial infarction; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; THC, Δ9-tetrahydrocannabinol.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>REACTION</b></td><td align="LEFT" valign="BOTTOM"><b>DRUG(S)</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Blood Dyscrasias</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aplastic anemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chloramphenicol, alkylating agents </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemolytic anemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Penicillin, methyldopa, quinidine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Macrocytic anemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Methotrexate (most common), phenytoin, oral contraceptives, 5-fluorouracil </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Platelet dysfunction </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aspirin, other NSAIDs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thrombocytopenia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Heparin (most common cause in hospital), quinidine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Cardiac</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dilated cardiomyopathy </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Doxorubicin, daunorubicin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Central Nervous System</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tinnitus, vertigo </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Salicylates </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Cutaneous</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Angioedema </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ACE inhibitors (↑ bradykinin) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Maculopapular rash </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Penicillin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Photosensitive rash </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tetracycline </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Urticaria </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Penicillin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Gastrointestinal</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemorrhagic gastritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Iron, salicylates </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Hepatic</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cholestasis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oral contraceptives, estrogen, anabolic steroids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fatty change </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Amiodarone, tetracycline, methotrexate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatic adenoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oral contraceptives, anabolic steroids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Liver necrosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acetaminophen (most common), isoniazid, salicylates, halothane, iron </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Pulmonary</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Asthma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aspirin, other NSAIDs </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Interstitial fibrosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bleomycin, busulfan, nitrofurantoin, methotrexate </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> <b>Systemic</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drug-induced lupus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Procainamide, hydralazine </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>ACE, angiotensin-converting enzyme.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CHEMICAL</b></td><td align="LEFT" valign="BOTTOM"><b>SOURCE</b></td><td align="LEFT" valign="BOTTOM"><b>TOXIC EFFECTS/TREATMENT</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Arsenic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pesticides, contaminated ground water </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibits enzymes that require lipoic acid as a cofactor (e.g., pyruvate dehydrogenase) causing increased conversion of pyruvate to lactate. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Severe headaches, abdominal pain, diarrhea, delirium, convulsions, transverse bands in nails (Mees lines), death. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Squamous cell carcinoma of skin, liver angiosarcoma, lung cancer </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: chelating agents:succimer (2,3-dimercaptosuccinic acid) or dimercaprol (BAL) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Asbestos (refer to <span macro="tag [[16 Upper and Lower Respiratory Disorders]] [[Chapter 16]]"></span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insulation, roofing material </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary lung cancer, mesothelioma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Benzene </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Solvent </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute leukemia, aplastic anemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Carbon monoxide (CO) (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Automobile exhaust, house fires, generators </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Headache (first sign), cherry-red skin, coma<br>↓ O<sub>2</sub> saturation, normal Pa<span style="font-variant:small-caps;">o</span><sub>2</sub>; lactic acidosis (due to hypoxia)<br><i>Treatment</i>: O<sub>2</sub> via nonbreather mask or endotracheal tube (100% O<sub>2</sub>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cyanide (CN) (refer to <span macro="tag [[01 Cell Injury]] [[Chapter 1]]"></span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> House fires </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Odor of bitter almonds; coma, seizures, heart dysfunction, metabolic acidosis (serum lactate >10 mmol/L), due to inhibition of cytochrome oxidase in ETC and subsequent shift to anaerobic glycolysis as only ATP source </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: amyl nitrite (produces metHb which combines with CN to form cyanmetHb) followed by thiosulfate (CN converted to thiocyanate) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ethylene glycol (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antifreeze<br>End-product: oxalic acid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased anion gap metabolic acidosis<br>Acute renal failure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: IV infusion of ethanol or 4-methylpyrazole (see <span>[[Table 4-6|Table 4-6. CAUSES OF INCREASED ANION GAP METABOLIC ACIDOSIS]]</span> for discussion) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Isopropyl alcohol </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rubbing alcohol </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fruity odor to breath (acetone); can progress into deep coma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> End-product: acetone </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Does <i>not</i> produce increased anion gap like ethanol, methanol, ethylene glycol but does increase osmolal gap (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: hemodialysis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lead (refer to <span macro="tag [[11 Red Blood Cell Disorders]] [[Chapter 11]]"></span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lead-based paint, batteries, metal casting </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Microcytic anemia with coarse basophilic stippling, nephrotoxicity in proximal tubule </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: chelating agents: succimer, dimercaprol (BAL), EDTA </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mercury </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fish most important source </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diarrhea, constricted visual fields, nephrotoxicity in proximal tubule, tachycardia, hyperhidrosis (↑ sweating), peripheral neuropathy, hypertension </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: chelating agents: succimer, penicillamine, or dimercaprol (BAL) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Methanol (refer to <span macro="tag [[04 Water, Electrolyte, Acid-Base, and Hemodynamic Disorders]] [[Chapter 4]]"></span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Windshield-washer fluid<br>End-product: formic acid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased anion gap metabolic acidosis<br>Blindness due to optic atrophy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: IV infusion of ethanol or 4-methylpyrazole (see <span>[[Table 4-6|Table 4-6. CAUSES OF INCREASED ANION GAP METABOLIC ACIDOSIS]]</span> for discussion) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Organophosphates </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pesticides </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Salivation, lacrimation, urinary/fecal incontinence, diaphoresis, blurred vision, hypotension, bradycardia, muscle fasiculations </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased serum and RBC cholinesterase levels </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: atropine; pralidoxime has also been used </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Polyvinyl chloride </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Plastics industry </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Liver angiosarcoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>ATP, adenosine triphosphate; BAL, British anti-lewisite; EDTA, ethylenediamine-tetraacetic acid; ETC, electron transport chain.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>AGENT</b></td><td align="LEFT" valign="BOTTOM"><b>VENOM</b></td><td align="LEFT" valign="BOTTOM"><b>TOXIC EFFECTS/TREATMENT</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Coral snake (elapid) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neurotoxin: binds to presynaptic nerve terminals and acetylcholine </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Snake has "red on yellow" bands (red and yellow kill a fellow); "red on black" is a harmless scarlet king snake (red and black friend of jack) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Toxic effects: paralysis (diplopia, respiratory muscles), fixed and contracted pupils; death by respiratory failure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: elapid antivenin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rattlesnake, copperhead, water moccasin (crotalids) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Venom cytohemoneurotoxic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Toxic effects: local edema/pain with progressive development of ecchymoses and bleeding into tissue, shock, DIC<br><i>Treatment</i>: avoid tourniquets and suction/incision kits; constriction bands above bite to reduce venous/lymphatic flow but maintain pulse; sheep antivenin (equine discontinued) with monospecific antibodies. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Latrodectus</i> (black widow spider) (see <span>[[Fig. 6-2A|Figure 6-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Latrotoxin (acts through Ca<sup>2+</sup>-mediated channels to cause release of acetylcholine and norepinephrine from nerve terminals) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Painful bite followed by increasing local pain; small erythematous macule develops within an hour which develops into a "target" lesion with a pale center surrounded by erythema; severe muscle cramps/spasms develop in trunk, thighs, and abdomen, the latter simulating an acute abdomen; hypertension may occur. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: supportive; <i>Latrodectus</i> antivenom is available </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Loxosceles</i> (brown recluse spider) (see <span>[[Fig. 6-2B|Figure 6-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Necrotoxins </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Initially painless bite; painful reddish blister in several hours that develops a bluish discoloration in 24 hours; extensive skin necrosis occurs over next 3-4 days, with eschar formation by the end of the first week; may become infected; surgical débridement may be necessary. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: supportive measures; antibiotics if necessary </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Scorpion (see <span>[[Fig. 6-2C|Figure 6-2]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neurotoxin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Poisonous species in southwestern U.S. deserts (<i>Centruroides</i> sp.) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Toxic effects: initially has painful sting followed by numbness, hypertension, ascending motor paralysis leading to death. May cause acute pancreatitis. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: supportive; antivenom (goat serum) only with severe toxicity </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bees, wasps, hornets </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Histamine and other components </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> As a group, they are the most common cause of death due to a venomous bite in the United States. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Reactions range from localized erythema and swelling to an anaphylactic reaction (dyspnea, wheezing, inspiratory stridor [laryngeal swelling], shock, death) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: epinephrine 0.3-0.5 mL of 1:1000 concentration intramuscularly in adults; 0.01 mg/kg in children; long-term management: insect sting kit with premeasured epinephrine; skin desensitization </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fire ants </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insoluble alkaloid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Swarm when provoked and attack in great numbers; painful bites with papules becoming sterile pustules in several hours; necrosis, scarring, secondary infection can occur; death may occur in some cases. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: local wound care; desensitization is available </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>DIC, disseminated intravascular coagulation.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TYPE OF INJURY</b></td><td align="LEFT" valign="BOTTOM"><b>BODY TEMPERATURE</b></td><td align="LEFT" valign="BOTTOM"><b>SKIN</b></td><td align="LEFT" valign="BOTTOM"><b>MENTAL STATUS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Heat cramps </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 37°C (98.6°F) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Moist and cool </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Heat exhaustion </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ≤40°C (104°F) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sweating </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Normal </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Heat stroke </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> >40°C (>104°F) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dry (anhidrosis) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Impaired consciousness<br>CNS dysfunction </td></tr></tbody></table><a name=""></a> <br>*Heat injury is exacerbated by high humidity.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CLINICAL FINDING</b></td><td align="LEFT" valign="BOTTOM"><b>COMMENTS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cancer </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased incidence of estrogen-related cancers (e.g., endometrial, breast) because of increased aromatization of androgens to estrogens in adipose tissue </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cholelithiasis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased incidence of cholecystitis and cholesterol stones: bile is supersaturated with cholesterol </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diabetes mellitus, type 2 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased adipose downregulates insulin receptor synthesis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hyperinsulinemia increases adipose stores </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Weight reduction upregulates insulin receptor synthesis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatomegaly </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fatty change accompanied by liver cell injury and repair by fibrosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypertension </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hyperinsulinemia increases sodium retention, leading to increase in plasma volume </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Left ventricular hypertrophy and stroke complicate hypertension </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypertriglyceridemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypertriglyceridemia decreases serum high-density lipoprotein levels, increasing risk of coronary artery disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased low-density lipoprotein levels </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypercholesterolemia predisposes to coronary artery disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Obstructive sleep apnea </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Weight of adipose tissue compresses upper airways causing respiratory acidosis and hypoxemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Potential for developing cor pulmonale (pulmonary hypertension and right ventricular hypertrophy) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osteoarthritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Degenerative arthritis in weight-bearing joints (e.g., femoral heads) </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>VITAMIN</b></td><td align="LEFT" valign="BOTTOM"><b>EFFECTS OF DEFICIENCY</b></td><td align="LEFT" valign="BOTTOM"><b>EFFECTS OF TOXICITY</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> A </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Impaired night vision, blindness (squamous metaplasia of corneal epithelium; see <span>[[Fig. 7-4A|Figure 7-4]]</span>)<br>Follicular hyperkeratosis (loss of sebaceous gland function; see <span>[[Fig. 7-4B|Figure 7-4]]</span>), pneumonia, growth retardation, renal calculi </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Papilledema and seizures (due to an increase in intracranial pressure), hepatitis, bone pain (due to periosteal proliferation) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> D </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pathologic fractures, excess osteoid, bow legs (see <span>[[Fig. 7-4C|Figure 7-4]]</span>)<br>Children: rickets; craniotabes (soft skull bones); rachitic rosary (defective mineralization and overgrowth of epiphyseal cartilage in ribs) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypercalcemia with metastatic calcification, renal calculi </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adults: called osteomalacia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Continuous muscle contraction (tetany) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> E </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemolytic anemia (damage to RBC membrane)<br>Peripheral neuropathy, degeneration of posterior column (poor joint sensation) and spinocerebellar tract (ataxia) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Decreased synthesis of vitamin K-dependent procoagulant factors; synergistic effect with warfarin anticoagulation </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> K </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Newborns: hemorrhagic disease of newborn (CNS bleeding, ecchymoses)<br>Adults: gastrointestinal bleeding, ecchymoses; prolonged prothrombin time and partial thromboplastin time </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hemolytic anemia and jaundice in newborns if mother receives excess vitamin K </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>VITAMIN</b></td><td align="LEFT" valign="BOTTOM"><b>EFFECTS OF DEFICIENCY</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thiamine (vitamin B<sub>1</sub>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dry beriberi: peripheral neuropathy (demyelination) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wernicke's syndrome: ataxia, confusion, nystagmus, mamillary body hemorrhage </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Korsakoff's syndrome: antegrade and retrograde amnesia; demyelination in limbic system </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wet beriberi: congestive cardiomyopathy with biventricular failure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Riboflavin (vitamin B<sub>2</sub>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Corneal neovascularization, glossitis, cheilosis (cracked lips), angular stomatitis (fissuring at angles of mouth) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Niacin (vitamin B<sub>3</sub>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pellagra: diarrhea, dermatitis (hyperpigmentation in sun-exposed areas; see <span>[[Fig. 7-5A|Figure 7-5]]</span>), dementia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pyridoxine (vitamin B<sub>6</sub>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sideroblastic anemia (microcytic anemia with ringed sideroblasts; see <span>[[Fig. 11-13|Figure 11-13]]</span>), convulsions, peripheral neuropathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cobalamin (vitamin B<sub>12</sub>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Megaloblastic anemia, neurologic disease (posterior column and lateral corticospinal tract demyelination), glossitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Folic acid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Megaloblastic anemia, with <i>no</i> neurologic disease (unlike vitamin B<sub>12</sub>), glossitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Biotin </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dermatitis, alopecia, lactic acidosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Ascorbic acid (vitamin C) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Weak capillaries and venules, skin ecchymoses, perifollicular hemorrhage (ring of hemorrhage around hair follicles; see <span>[[Fig. 7-5B|Figure 7-5]]</span>), corkscrew hairs (see <span>[[Fig. 7-5C|Figure 7-5]]</span>), hemarthrosis, bleeding gums (see <span>[[Fig. 7-5D|Figure 7-5]]</span>), anemia (combined iron and folate deficiency) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Loosened teeth, glossitis, poor wound healing </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TRACE METAL</b></td><td align="LEFT" valign="BOTTOM"><b>EFFECTS OF DEFICIENCY</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chromium </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metabolic: impaired glucose tolerance, peripheral neuropathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Copper </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Blood: microcytic anemia (cofactor in ferroxidase) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vessels: aortic dissection (weak elastic tissue) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metabolic: poor wound healing (cofactor in lysyl oxidase) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fluoride </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Teeth: dental caries </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Iodide </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thyroid: thyroid enlargement (goiter), hypothyroidism </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Selenium </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Muscle: muscle pain and weakness, dilated cardiomyopathy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Zinc </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Metabolic: poor wound healing (cofactor in collagenase) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Mouth: dysgeusia (cannot taste), anosmia (cannot smell), perioral rash </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Children: hypogonadism, growth retardation </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CATEGORY</b></td><td align="LEFT" valign="BOTTOM"><b>CANCER</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal dominant cancer syndromes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <b>Retinoblastoma:</b> malignancy of eye in children; 40% are inherited; point mutation inactivates <i>RB</i> suppressor gene on chromosome 13; one gene inactivated in germ cells, remaining gene inactivated after birth (two-hit theory); predisposition for osteogenic sarcoma in adolescence </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <b>Familial adenomatous polyposis:</b> development of colorectal cancer from malignant transformation of polyps by age 50; inactivation of <i>APC</i> suppressor gene </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <b>Li-Fraumeni syndrome:</b> increased risk for sarcomas, leukemia, carcinomas (e.g., breast) before age 50; inactivation of <i>TP53</i> suppressor gene </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <b>Hereditary nonpolyposis colon cancer (Lynch syndrome):</b> increased risk for colorectal cancers <i>without</i> previous polyps; inactivation of DNA mismatch repair genes; cannot correct errors in nucleotide pairing; characteristic finding is alteration in microsatellite nucleotide sequences (normally do not change in cells) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <b><i>BRCA<sub>1</sub></i></b> and <b><i>BRCA<sub>2</sub></i></b> <b>genes:</b> inactivation of genes increases risk for developing breast and ovarian cancer </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Autosomal recessive syndromes with defects in DNA repair (see <span>[[Fig. 8-3|Figure 8-3]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <b>Xeroderma pigmentosum:</b> increased risk for developing skin cancers due to ultraviolet light (cross-links adjacent pyrimidine producing pyrimidine dimers); examples include basal cell carcinoma, squamous cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <b>Chromosome instability syndromes:</b> chromosomes susceptible to damage by ionizing radiation and drugs; predisposition to cancers (e.g., leukemia, lymphoma); disorders include Fanconi anemia, ataxia telangiectasia, Bloom syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Familial cancer syndromes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> No defined pattern of inheritance, but cancers (e.g., breast, ovary, colon) develop with increased frequency in families; sometimes involves <i>BRCA1</i> and <i>BRCA2</i> genes </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>PRECURSOR LESION</b></td><td align="LEFT" valign="BOTTOM"><b>CANCER</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Actinic (solar) keratosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Squamous cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Atypical hyperplasia of ductal epithelium of breast </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic irritation at sinus orifice, third-degree burn scars </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Squamous cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic ulcerative colitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Complete hydatidiform mole </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Choriocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dysplastic nevus </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant melanoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Endometrial hyperplasia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glandular metaplasia of esophagus (Barrett's esophagus) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glandular metaplasia of stomach (<i>Helicobacter pylori</i>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Myelodysplastic syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute leukemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Regenerative nodules in cirrhosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Scar tissue in lung </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Squamous dysplasia of oropharynx, larynx, bronchus, cervix </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Squamous cell carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Tubular adenoma of colon </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vaginal adenosis (diethylstilbestrol exposure) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Villous adenoma of rectum </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma </td></tr></tbody></table><a name=""></a> <br>*Metaplastic and hyperplastic cells become dysplastic <i>before</i> progressing to cancer.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>PROTO-ONCOGENE</b></td><td align="LEFT" valign="BOTTOM"><b>FUNCTION</b></td><td align="LEFT" valign="BOTTOM"><b>MUTATION</b></td><td align="LEFT" valign="BOTTOM"><b>CANCER</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>ABL</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nonreceptor tyrosine kinase activity </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Translocation t(9;22) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic myelogenous leukemia (chromosome 22 is Philadelphia chromosome) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>HER</i> (<i>ERBB2</i>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Receptor synthesis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Amplification </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Breast carcinoma (marker of aggressiveness) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>MYC</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nuclear transcription </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Translocation t(8;14) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Burkitt's lymphoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>N-MYC</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nuclear transcription </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Amplification </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neuroblastoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>RAS</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Guanosine triphosphate signal transduction </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Point mutation </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Leukemia; lung, colon, pancreatic carcinomas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>RET</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Receptor synthesis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Point mutation </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Multiple endocrine neoplasia IIa/IIb syndromes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>SIS</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Growth factor synthesis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Overexpression </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Osteogenic sarcoma, astrocytoma </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>GENE</b></td><td align="LEFT" valign="BOTTOM"><b>FUNCTION</b></td><td align="LEFT" valign="BOTTOM"><b>ASSOCIATED CANCERS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>APC</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prevents nuclear transcription (degrades catenin, an activator of nuclear transcription) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Familial polyposis (colorectal carcinoma) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>BRCA1</i>/<i>BRCA2</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Regulates DNA repair </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Breast, ovary, prostate carcinomas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>RB</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibits G<sub>1</sub> to S phase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Retinoblastoma, osteogenic sarcoma, breast carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>TGF</i>-β </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibits G<sub>1</sub> to S phase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pancreatic and colorectal carcinomas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>TP53</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Inhibits G<sub>1</sub> to S phase </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lung, colon, breast carcinomas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Repairs DNA, activates <i>BAX</i> gene (initiates apoptosis) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Li-Fraumeni syndrome: breast carcinoma, brain tumors, leukemia, sarcomas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>VHL</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Regulates nuclear transcription </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Von Hippel-Lindau syndrome: cerebellar hemangioblastoma, retinal angioma, renal cell carcinoma (bilateral), pheochromocytoma (bilateral) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>WT1</i> </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Regulates nuclear transcription </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wilms' tumor </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br><i>APC</i>, adenomatous polyposis coli; <i>BRCA</i>, breast cancer; <i>RB</i>, retinoblastoma; <i>TGF-</i>β, transforming growth factor β; <i>VHL</i>, von Hippel-Lindau; <i>WT</i>, Wilms' tumor.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>CARCINOGEN</b></td><td align="LEFT" valign="BOTTOM"><b>ASSOCIATED CANCER</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aflatoxin (from <i>Aspergillus</i>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatocellular carcinoma in association with hepatitis B virus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alcohol </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Squamous cell carcinoma of oropharynx and upper/middle esophagus; pancreatic and hepatocellular carcinomas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Alkylating agents </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant lymphoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Arsenic </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Squamous cell carcinoma of skin, lung cancer, liver angiosarcoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Asbestos </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchogenic carcinoma, pleural mesothelioma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Benzene </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute leukemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Beryllium </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchogenic carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chromium </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchogenic carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cyclophosphamide </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transitional cell carcinoma of urinary bladder </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Diethylstilbestrol </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Clear cell carcinoma of vagina/cervix </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> β-Naphthylamine (aniline dyes) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transitional cell carcinoma of urinary bladder </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nickel </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchogenic carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oral contraceptives </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Breast, cervical carcinomas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Polycyclic hydrocarbons </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Squamous cell carcinoma: oral cavity, midesophagus, larynx, lung </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adenocarcinoma: distal esophagus, pancreas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Transitional cell carcinoma: urinary bladder, renal pelvis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Polyvinyl chloride </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Liver angiosarcoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Silica </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bronchogenic carcinoma </td></tr></tbody></table><a name=""></a>
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>VIRUS</b></td><td align="LEFT" valign="BOTTOM"><b>MECHANISM</b></td><td align="LEFT" valign="BOTTOM"><b>ASSOCIATED CANCER</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>RNA Viruses</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HCV </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Produces postnecrotic cirrhosis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatocellular carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HTLV-1 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Activates <i>TAX g</i>ene, stimulates polyclonal T-cell proliferation, inhibits <i>TP53</i> suppressor gene </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> T-cell leukemia and lymphoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> <b>DNA Viruses</b> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> EBV </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Promotes polyclonal B-cell proliferation, which increases risk for t(8;14) translocation </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Burkitt's lymphoma, CNS lymphoma in AIDS, mixed cellularity Hodgkin's lymphoma, nasopharyngeal carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HBV </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Activates proto-oncogenes, inactivates <i>TP53</i> suppressor gene </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatocellular carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HHV-8 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acts via cytokines released from HIV and HSV </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Kaposi's sarcoma in AIDS </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> HPV types 16 and 18 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Type 16 (∼ 50% of cancers): E6 gene product inhibits <i>TP53</i> suppressor gene<br>Type 18 (∼ 10% of cancers): E7 gene product inhibits <i>RB</i> suppressor gene </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Squamous cell carcinoma of vulva, vagina, cervix, anus (associated with anal intercourse), larynx, oropharynx </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>EBV, Epstein-Barr virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HHV, human herpesvirus; HPV, human papillomavirus; HSV, herpes simplex virus; HTLV, human T-cell lymphotropic virus.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>ASSOCIATED CANCER</b></td><td align="LEFT" valign="BOTTOM"><b>ECTOPIC HORMONE</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cushing syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small cell carcinoma of lung, medullary carcinoma of thyroid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> ACTH </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Gynecomastia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Choriocarcinoma (testis) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> hCG </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypercalcemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal cell carcinoma, primary squamous cell carcinoma of lung, breast carcinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> PTH-related protein<br>Calcitriol (vitamin D) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant lymphomas (contain 1α-hydroxylase) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypocalcemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Medullary carcinoma of thyroid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Calcitonin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypoglycemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatocellular carcinoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Insulin-like factor </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hyponatremia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small cell carcinoma of lung </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Antidiuretic hormone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Secondary polycythemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal cell and hepatocellular carcinomas </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Erythropoietin </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="3"> </td></tr></tbody></table><a name=""></a> <br>ACTH, adrenocorticotropic hormone; hCG, human chorionic gonadotropin; PTH, parathyroid hormone.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TUMOR MARKER</b></td><td align="LEFT" valign="BOTTOM"><b>ASSOCIATED CANCER</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> AFP </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hepatocellular carcinoma, yolk sac tumor (endodermal sinus tumor) of ovary or testis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bence Jones protein </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Multiple myeloma, Waldenström's macroglobulinemia (represent light chains in urine) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CA 15-3 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Breast carcinoma </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CA 19-9 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pancreatic, colorectal carcinomas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CA 125 </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Surface-derived ovarian cancer (e.g., serous cystadenocarcinoma; helpful in distinguishing benign from malignant tumors) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CEA </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Colorectal and pancreatic carcinomas (monitor for recurrences) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> LDH </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant lymphoma (prognostic factor for response to standard therapy) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> PSA </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Prostate carcinoma (also increased in prostate hyperplasia) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>AFP, α-fetoprotein; CEA, carcinoembryonic antigen; LDH, lactate dehydrogenase; PSA, prostate-specific antigen.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>TUMOR/CONDITION</b></td><td align="LEFT" valign="BOTTOM"><b>CLINICAL FINDINGS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Angiomyolipoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Kidney hamartoma, composed of blood vessels, muscle, and mature adipose tissue </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Association with tuberous sclerosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Angiosarcoma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Liver angiosarcoma associated with exposure to polyvinyl chloride, arsenic, thorium dioxide </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Bacillary angiomatosis (see <span>[[Fig. 9-9A|Figure 9-9]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Benign capillary proliferation involving skin and visceral organs in AIDS patients </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Simulates Kaposi's sarcoma in AIDS </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Caused by <i>Bartonella henselae</i>, a gram-negative bacillus </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Capillary hemangioma (see <span>[[Fig. 9-9B|Figure 9-9]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Facial lesion in newborns that regresses with age </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cavernous hemangioma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most common benign tumor of liver and spleen </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> May rupture if large </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cystic hygroma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lymphangioma in the neck associated with Turner's syndrome </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Glomus tumor </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Derive from arteriovenous shunts in glomus bodies </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Painful red subungual nodule in a digit </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hereditary telangiectasia (AD) (see <span>[[Fig. 9-9C|Figure 9-9]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Dilated vessels on skin and mucous membranes in mouth and gastrointestinal tract </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Chronic iron deficiency anemia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Kaposi's sarcoma (see <span>[[Fig. 3-4|Figure 3-4]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant tumor arising from endothelial cells or primitive mesenchymal cells </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with human herpesvirus type 8 </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Raised, red-purple discoloration that progresses from a flat lesion to a plaque to a nodule that ulcerates </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Common sites include skin (most common site), mouth, and gastrointestinal tract </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lymphangiosarcoma (see <span>[[Fig. 9-8|Figure 9-8]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignancy of lymphatic vessels </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Arises out of long-standing chronic lymphedema (e.g., after modified radical mastectomy) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pyogenic granuloma </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vascular, red pedunculated mass that ulcerates and bleeds easily </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Post-traumatic or associated with pregnancy (relation to estrogen); usually regress postpartum </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Spider telangiectasia (see <span>[[Fig. 18-10|Figure 18-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Arteriovenous fistula (disappears when compressed) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Associated with hyperestrinism (e.g., cirrhosis, pregnancy) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Sturge-Weber syndrome (see <span>[[Fig. 9-9D|Figure 9-9]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Nevus flammeus ("birthmark") on the face in distribution of ophthalmic branch of cranial nerve V (trigeminal) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Some cases show ipsilateral malformation of pia mater vessels overlying occipital and parietal lobes </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Von Hippel-Lindau syndrome (AD) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cavernous hemangiomas in cerebellum and retina </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased incidence of pheochromocytoma and bilateral renal cell carcinomas </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>AD, autosomal dominant.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>DISORDER</b></td><td align="LEFT" valign="BOTTOM"><b>VASCULITIS</b></td><td align="LEFT" valign="BOTTOM"><b>EPIDEMIOLOGY/ETIOLOGY</b></td><td align="LEFT" valign="BOTTOM"><b>CLINICAL/LABORATORY FINDINGS/TREATMENT</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Takayasu arteritis ("pulseless disease") </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Granulomatous large vessel vasculitis involving aortic arch vessels </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Young Asian women and children </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Absent upper extremity pulse<br>Discrepancy in blood pressure between arms > 10 mm Hg<br>Visual defects, stroke </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Giant cell (temporal) arteritis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Granulomatous large vessel vasculitis involving superficial temporal and ophthalmic arteries. </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adults > 50 years of age </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Temporal headache, jaw claudication (pain when chewing stretches inflamed artery)<br>Blindness on ipsilateral side<br>Polymyalgia rheumatica (muscle and joint pain; normal serum creatine kinase) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Increased ESR </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Polyarteritis nodosa (see <span>[[Fig. 9-10A|Figure 9-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Necrotizing medium-sized vessel vasculitis involving renal, coronary, mesenteric arteries (spares pulmonary arteries) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Middle-aged men<br>Association with HBsAg (30%) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vessels at all stages of acute and chronic inflammation<br>Focal vasculitis produces aneurysms (detected with angiography)<br>Organ infarction in kidneys (renal failure), heart (acute MI), bowels (bloody diarrhea), skin (ischemic ulcer), testicle (testicular pain) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Angiography and biopsy of lesions confirm the diagnosis. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Kawasaki disease (see <span>[[Fig. 9-10B|Figure 9-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Necrotizing medium-sized vessel vasculitis involving coronary arteries (e.g., thrombosis, aneurysms) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Children < 5 years of age<br>Boys > girls<br>Cause unknown (probably infectious)<br>Children of Asian descent have highest incidence </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Fever, erythema and edema of hands and feet convalescing with desquamated rash; cervical adenopathy; oral erythema and cracking of the lips<br>Abnormal ECG (e.g., acute MI) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Surpassed acute rheumatic heart disease as most common acquired heart disease in children </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: intravenous immunoglobulin; aspirin; corticosteroids contraindicated (danger of vessel rupture) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thromboangiitis obliterans (Buerger's disease) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Medium-sized vessel vasculitis with digital vessel thrombosis and damage to neurovascular compartment </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Men 25-50 years of age who smoke cigarettes<br>Middle East, Far East, Asia has highest prevalence </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Resting pain on the forefoot is characteristic, with possible ischemic ulcers or gangrene of foot/toes; upper limb ischemia (40% to 50% of patients) with ulceration and gangrene; Raynaud's phenomenon. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: smoking cessation essential; intravenous iloprost (prostaglandin analogue) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Raynaud's disease </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Medium-sized vessel vasculitis involving digital vessels in fingers and toes; also tip of nose and ears in some cases </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Young women<br>Exaggerated vasomotor response to cold or stress </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Paroxysmal digital color changes (white-blue-red sequence)<br>Ulceration and gangrene in chronic cases<br><i>Treatment</i>: avoid cold temperatures (gloves); calcium channel blockers (e.g., nifedipine) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Raynaud's phenomenon (see <span>[[Fig. 9-10C|Figure 9-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Medium-sized vessel vasculitis involving digital vessels in fingers and toes; also tip of nose and ears in some cases </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adult men and women<br>Secondary to other diseases (e.g., systemic sclerosis, CREST syndrome, SLE) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Systemic sclerosis and CREST syndrome (see <a title="Go here now" href="/content/bookcontent.cfm?xrefID=P0047#P0047" type="PAGE">page 47</a>): digital vasculitis with vessel fibrosis, dystrophic calcification, ulceration, gangrene<br><i>Treatment</i>: see above </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Wegener's granulomatosis (see <span>[[Fig. 9-10D|Figure 9-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Necrotizing medium and small-sized vessel vasculitis involving lung (infarctions, renal vessels) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Childhood to middle age </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Necrotizing granulomas in skin, upper respiratory tract (nasopharynx-saddle nose deformity, chronic sinusitis, collapse of trachea), lower respiratory tract (cavitating nodular lesions)<br>Necrotizing vasculitis in lungs (infarction, hemoptysis), kidneys (crescentic glomerulonephritis) c-ANCA antibodies (>90% of cases) correlate erratically with therapy </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroids, cyclo-phosphamide </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 3 Cs: c-ANCA, corticosteroids, cyclophosphamide </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Microscopic polyangiitis </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small vessel vasculitis involving skin, lung, brain, GI tract, and postcapillary venules and glomerular capillaries </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Children and adults<br>Precipitated by drugs (e.g., penicillin), infections (e.g., streptococci), immune disorders (e.g., SLE) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Vessels at same stage of inflammation<br>Palpable purpura, glomerulonephritis<br>p-ANCA antibodies (>80% of cases) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Churg-Strauss syndrome </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small vessel vasculitis involving skin, lung, heart vessels </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Children and adults </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Allergic rhinitis, asthma<br>p-ANCA antibodies (70% of cases), eosinophilia </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Henoch-Schönlein purpura (see <span>[[Fig. 9-10E|Figure 9-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small vessel vasculitis involving skin, GI, renal, joint vessels </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Children and young adults<br>Males > females<br>Most common vasculitis in children<br>IgA-anti-IgA immunocomplexes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Often follows a viral URI, group A streptococcal pharyngeal infection-pathogens may act as an antigen trigger that causes antibody formation leading to immunocomplex formation<br>Palpable purpura of buttocks and lower extremities </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Polyarthritis (80%), nephropathy (80%), GI bleeding </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Recurrence may occur in one third of cases </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Most have spontaneous recovery in 4 months without therapy. </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> <i>Treatment</i>: corticosteroids mainly used if severe GI disease or renal disease </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cryoglobulinemia </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small vessel vasculitis involving skin, GI tract, renal vessels<br>Different types of cryoglobulinemia (mixed, monoclonal, polyclonal) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adults<br>Association with HCV, type I MPGN, multiple myeloma (monoclonal type) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cryoglobulins: immunoglobulins that gel at cold temperatures<br>Palpable purpura, acral cyanosis of nose and ears and Raynaud's phenomenon (reverses when in warm room); glomerulonephritis; arthritis; abdominal pain </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Infectious vasculitis (see <span>[[Fig. 9-10F|Figure 9-10]]</span>) </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Small vessel vasculitis involving skin vessels </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Children and adults<br>Involves all microbial pathogens </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Rocky Mountain spotted fever: tick transmission of <i>Rickettsia rickettsiae</i><br>Organisms invade endothelial cells producing vasculitis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Petechiae on palms spread to trunk </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Disseminated meningococcemia due to <i>Neisseria meningitides</i> </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Capillary thrombosis produces hemorrhage into skin and confluent ecchymoses </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="4"> </td></tr></tbody></table><a name=""></a> <br>c-ANCA, cytoplasmic antineutrophil cytoplasmic antibodies; ECG, electrocardiogram; ESR, erythrocyte sedimentation rate; GI, gastrointestinal; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; MI, myocardial infarction; MPGN, membranoproliferative glomerulonephritis; p-ANCA, perinuclear antineutrophil cytoplasmic antibodies; SLE, systemic lupus erythematosus; URI, upper respiratory infection.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>SYSTEM OR SOURCE</b></td><td align="LEFT" valign="BOTTOM"><b>DESCRIPTION</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Adrenal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cushing syndrome: increased mineralocorticoids </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pheochromocytoma: increased catecholamines </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Neuroblastoma: increased catecholamines </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> 11-Hydroxylase deficiency: increased mineralocorticoids (i.e., deoxycorticosterone) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary aldosteronism (Conn's syndrome): increased aldosterone </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Aorta </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Postductal coarctation: activation of RAA system </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Elderly: systolic hypertension due to decreased elasticity of the aorta </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> CNS </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intracranial hypertension: release of catecholamines </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Drugs </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Oral contraceptive: increased synthesis of angiotensinogen; most common cause of hypertension in young women </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cocaine: increased sympathetic activity </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Parathyroid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Primary hyperparathyroidism: calcium increases peripheral resistance arteriole smooth muscle cell contraction </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Pregnancy </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Preeclampsia: increased angiotensin II </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renovascular disease: atherosclerosis (elderly men), fibromuscular hyperplasia (women) </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal parenchymal disease: e.g., diabetic nephropathy, adult polycystic kidney disease, glomerulonephritis; retention of sodium </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Thyroid </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Graves' disease: systolic hypertension from increased cardiac contraction </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypothyroidism: diastolic hypertension due to retention of sodium </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP" colspan="2"> </td></tr></tbody></table><a name=""></a> <br>RAA, renin-angiotensin-aldosterone.
</html>
<html><table class="SCtable"><tbody><tr class="TH"><td align="LEFT" valign="BOTTOM"><b>SYSTEM</b></td><td align="LEFT" valign="BOTTOM"><b>COMPLICATIONS</b></td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Cardiovascular </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Left ventricular hypertrophy: most common overall complication </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Acute myocardial infarction: most common cause of death </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Atherosclerosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Central nervous </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Intracerebral hematoma: due to rupture of Charcot-Bouchard aneurysms </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Berry aneurysm: rupture produces a subarachnoid hemorrhage </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Lacunar infarcts: small infarcts due to hyaline arteriolosclerosis </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Renal </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Benign nephrosclerosis: kidney disease of hypertension; due to hyaline arteriolosclerosis; atrophy of tubules and sclerosis of glomeruli; progresses to renal failure </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"></td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Malignant hypertension: rapid increase in blood pressure accompanied by renal failure and cerebral edema </td></tr><tr class="TR"><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Eyes </td><td class="inline" bgcolor="FFFFFF" align="LEFT" valign="TOP"> Hypertensive retinopathy: arteriovenous nicking, hemorrhage of retinal vessels, exudates (increased vessel permeability, retinal infarction), papilledema </td></tr></tbody></table><a name=""></a>
</html>
/***
|Name|TableOfContentsPlugin|
|Source|http://www.TiddlyTools.com/#TableOfContentsPlugin|
|Documentation|http://www.TiddlyTools.com/#TableOfContentsPluginInfo|
|Version|2.4.3|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|replace the standard tabbed contents list with a scrolling listbox|
When there are many tiddlers in a document, the standard 'tabbed list of tiddlers' in the right-hand sidebar can become very long, occupying a lot of page space and requiring a lot scrolling in order to locate and select a tiddler. The TableOfContentsPlugin addresses this problem by replacing the standard tabbed list display with a single listbox/droplist control that uses a very small amount of page space, regardless of the number of tiddlers in the document.
!!!!!Documentation
>see [[TableOfContentsPluginInfo]]
!!!!!Configuration
<<option chkTOCShow>> display table of contents listbox
<<option chkTOCIncludeHidden>> include tiddlers tagged with <<tag excludeLists>> in listbox
listbox shows <<option txtTOCListSize>> lines, sorted by <<option txtTOCSortBy>>
!!!!!Revisions
<<<
2008.04.09 [2.4.3] restored config.options.chkTOCShow and onClickTOCMenu() handler
|please see [[TableOfContentsPluginInfo]] for additional revision details|
2005.06.13 [1.0.0] Initial Release (as adaptation - predates TiddlyWiki plugin architecture!!)
<<<
!!!!!Code
***/
//{{{
version.extensions.TableOfContentsPlugin= {major: 2, minor: 4, revision: 3, date: new Date(2008,4,9)};
//}}}
// // 1.2.x compatibility
//{{{
if (!window.story) window.story=window;
if (!store.getTiddler) store.getTiddler=function(title){return store.tiddlers[title]}
if (!store.addTiddler) store.addTiddler=function(tiddler){store.tiddlers[tiddler.title]=tiddler}
if (!store.deleteTiddler) store.deleteTiddler=function(title){delete store.tiddlers[title]}
//}}}
//{{{
// define defaults for cookie-based option values
if (config.options.txtTOCSortBy==undefined) config.options.txtTOCSortBy="modified";
if (config.options.txtTOCListSize==undefined) config.options.txtTOCListSize=19;
if (config.options.chkTOCShow==undefined) config.options.chkTOCShow=true;
if (config.options.chkTOCIncludeHidden==undefined) config.options.chkTOCIncludeHidden=false;
// define macro "tableOfContents" to render controls
config.macros.tableOfContents = { label: "contents" };
config.macros.tableOfContents.cmdMax=8; // index of maximum command item
config.macros.tableOfContents.css = '\
.TOC { padding:0.5em 1em 0.5em 1em; }\
.TOC a { padding:0em 0.25em 0em 0.25em; color:inherit; }\
.TOCList { width: 100%; font-size:8pt; margin:0em; }\
';
config.macros.tableOfContents.html = '\
<div style="text-align:right">\
<span style="float:left">\
<a href="JavaScript:;" id="TOCMenu" style="padding: 0em;"\
onclick="onClickTOCMenu(this)" title="show/hide table of contents">%label%</a>\
</span>\
<a href="JavaScript:;" id="TOCSmaller" style="display:inline"\
onclick="resizeTOC(this)" title="reduce list size">–</a>\
<a href="JavaScript:;" id="TOCLarger"style="display:inline"\
onclick="resizeTOC(this)" title="increase list size">+</a>\
<a href="JavaScript:;" id="TOCMaximize"style="display:inline"\
onclick="resizeTOC(this)" title="maximize/restore list size">=</a>\
</div>\
';
config.macros.tableOfContents.handler = function(place,macroName,params) {
var parsedParams = new Array();
parsedParams['label']=this.label;
parsedParams['inline']=false;
while (params.length>0) {
if (params[0]=="label:none") parsedParams['label']="";
else if (params[0].substr(0,6)=="label:") parsedParams['label']=params[0].substr(6);
if (params[0].substr(0,7)=="prompt:") parsedParams['prompt']=params[0].substr(7);
if (params[0].substr(0,8)=="padding:")parsedParams['padding']=params[0].substr(8);
if (params[0].substr(0,7)=="margin:") parsedParams['margin']=params[0].substr(7);
if (params[0].substr(0,5)=="sort:") parsedParams['sortby']=params[0].substr(5);
if (params[0].substr(0,5)=="date:") parsedParams['date']=params[0].substr(5);
if ((params[0]=="size:auto")||(params[0]=="size:0")) parsedParams['autosize']=true;
else if (params[0] && (params[0].substr(0,5)=="size:")) parsedParams['requestedSize']=params[0].substr(5);
if (params[0].substr(0,6)=="width:") parsedParams['width']=params[0].substr(6);
if (params[0]=="hidelist") parsedParams['hidelist']=true;
if (params[0]=="inline") parsedParams['inline']=true;
if (params[0]=="-title") parsedParams['hide_title']=true;
if (params[0]=="-date") parsedParams['hide_date']=true;
if (params[0]=="-author") parsedParams['hide_author']=true;
if (params[0]=="-creator") parsedParams['hide_creator']=true;
if (params[0]=="-tags") parsedParams['hide_tags']=true;
if (params[0]=="-missing") parsedParams['hide_missing']=true;
if (params[0]=="-orphans") parsedParams['hide_orphans']=true;
if (params[0]=="-shadows") parsedParams['hide_shadows']=true;
params.shift();
}
setStylesheet(config.macros.tableOfContents.css,"tableOfContents");
var newTOC=createTiddlyElement(place,parsedParams['inline']?"span":"div",null,"TOC",null)
if (parsedParams['margin']) { newTOC.style.margin=parsedParams['margin']; }
if (parsedParams['padding']) { newTOC.style.padding=parsedParams['padding']; }
if (parsedParams['label']!="") newTOC.innerHTML=config.macros.tableOfContents.html.replace(/%label%/,parsedParams['label']);
var newTOCList=createTOCList(newTOC,parsedParams)
refreshTOCList(newTOCList);
store.addNotification(null,reloadTOCLists); // reload listbox after every tiddler change
}
// IE needs explicit global scoping for functions/vars called from browser events
window.onChangeTOCList=onChangeTOCList;
window.onClickTOCList=onClickTOCList;
window.onDblClickTOCList=onDblClickTOCList;
window.reloadTOCLists=reloadTOCLists;
window.refreshTOCList=refreshTOCList;
window.onClickTOCMenu=onClickTOCMenu;
window.resizeTOC=resizeTOC;
function createTOCList(place,params) {
var list = createTiddlyElement(place,"select",null,"TOCList",params['prompt'])
list.params=params;
list.onchange=onChangeTOCList;
list.onclick=onClickTOCList;
list.ondblclick=onDblClickTOCList;
list.onkeyup=onKeyUpTOCList;
list.style.display=config.options.chkTOCShow ? "block" : "none" ;
list.sortBy=config.options.txtTOCSortBy;
list.dateFormat="DD MMM YYYY";
list.requestedSize=config.options.txtTOCListSize;
list.expandall=false;
list.cmdMax=config.macros.tableOfContents.cmdMax;
if (params['hide_title']) list.cmdMax--;
if (params['hide_date']) list.cmdMax--;
if (params['hide_author']) list.cmdMax--;
if (params['hide_creator']) list.cmdMax--;
if (params['hide_tags']) list.cmdMax--;
if (params['hide_missing']) list.cmdMax--;
if (params['hide_orphans']) list.cmdMax--;
if (params['hide_shadows']) list.cmdMax--;
if (params['sortby']) { list.sortBy=params['sortby']; list.noSortCookie=true; }
if (params['date']) { list.dateFormat=params['date']; }
if (params['autosize']) { list.autosize=true; list.noSizeCookie=true; }
if (params['requestedSize']){ list.requestedSize=params['requestedSize']; list.noSizeCookie=true; }
if (params['width']) { list.style.width=params['width']; }
if (params['hidelist']) { list.style.display ="none" ; list.noShowCookie=true; }
if (params['expandall']) { list.expandall=true; }
return list;
}
function onChangeTOCList() {
var thisTiddler=this.options[this.selectedIndex].value;
if ((this.size==1)&&(thisTiddler!='')&&(this.selectedIndex>this.cmdMax))
story.displayTiddler(null,thisTiddler,1);
refreshTOCList(this);
return false;
}
function onClickTOCList(e) {
if (!e) var e = window.event;
if (this.size==1) return; // don't toggle display for droplist
if (e.shiftKey) { this.expandall=!this.expandall; refreshTOCList(this);}
e.cancelBubble = true; if (e.stopPropagation) e.stopPropagation();
return true;
}
function onDblClickTOCList(e) {
if (!e) var e = window.event;
var thisTiddler=this.options[this.selectedIndex].value;
if ((thisTiddler!='')&&(this.selectedIndex>this.cmdMax))
story.displayTiddler(null,thisTiddler,1);
e.cancelBubble = true; if (e.stopPropagation) e.stopPropagation();
return false;
}
function onKeyUpTOCList(e) {
if (!e) var e = window.event;
if (e.keyCode!=13) return true;
var thisTiddler=this.options[this.selectedIndex].value;
if ((thisTiddler!='')&&(this.selectedIndex>this.cmdMax))
story.displayTiddler(null,thisTiddler,1);
e.cancelBubble = true; if (e.stopPropagation) e.stopPropagation();
return false;
}
function reloadTOCLists() {
var all=document.all? document.all.tags("select") : document.getElementsByTagName("select");
for (var i=0; i<all.length; i++)
if (all[i].className=="TOCList")
{ all[i].selectedIndex=-1; refreshTOCList(all[i]); }
}
function refreshTOCList(list) {
var selectedIndex = list.selectedIndex;
if (selectedIndex==-1) selectedIndex=0;
var sortBy = list.sortBy;
var showHidden = config.options.chkTOCIncludeHidden && !(config.options.chkHttpReadOnly && readOnly);
if (selectedIndex==0) sortBy=list.sortBy; // "nnn tiddlers" heading - use previous sort order
else if (selectedIndex<=list.cmdMax)sortBy=list.value;
else { if (list.options[list.selectedIndex].value=='') expandTOC(list); return; }
list.sortBy = sortBy; // save current sort order
if (!list.noSortCookie) { config.options.txtTOCSortBy=sortBy; saveOptionCookie("txtTOCSortBy"); }
// get the list of tiddlers
var tiddlers = [];
switch (sortBy) {
case "missing": tiddlers=store.getMissingLinks(); break;
case "tags": tiddlers=store.getTags(); break;
case "orphans": tiddlers=store.getOrphans(); break;
case "shadows": for (var t in config.shadowTiddlers) tiddlers.push(t); tiddlers.sort(); break;
default: tiddlers=store.getTiddlers(sortBy=='creator'?'modifier':sortBy,showHidden?'':'excludeLists'); break;
}
// clear current listbox contents
while (list.length > 0) { list.options[0] = null; }
list.saved=null;
// add heading and control items to list
var i=0;
var theHeading=tiddlers.length+' tiddlers:';
if (sortBy=='missing') theHeading=tiddlers.length+' missing tiddlers:';
if (sortBy=='orphans') theHeading=tiddlers.length+' orphaned tiddlers:';
if (sortBy=='tags') theHeading=tiddlers.length+' tags:';
if (sortBy=='shadows') theHeading=tiddlers.length+' shadow tiddlers:';
var indent=String.fromCharCode(160)+String.fromCharCode(160);
var sel=">";
list.options[i++]=new Option(theHeading,'');
function headerOpt(txt,val) { return new Option(((sortBy==val)?sel:indent)+' ['+txt+']',val); }
if (!list.params['hide_title']) list.options[i++]=headerOpt('by title','title');
if (!list.params['hide_date']) list.options[i++]=headerOpt('by date','modified');
if (!list.params['hide_author']) list.options[i++]=headerOpt('by author','modifier');
if (!list.params['hide_creator']) list.options[i++]=headerOpt('by creator','creator');
if (!list.params['hide_tags']) list.options[i++]=headerOpt('by tags','tags');
if (!list.params['hide_missing']) list.options[i++]=headerOpt('missing','missing');
if (!list.params['hide_orphans']) list.options[i++]=headerOpt('orphans','orphans');
if (!list.params['hide_shadows']) list.options[i++]=headerOpt('shadows','shadows');
// output the tiddler list
switch(sortBy) {
case "title":
for (var t = 0; t < tiddlers.length; t++)
list.options[i++] = new Option(tiddlers[t].title,tiddlers[t].title);
break;
case "modified":
case "modifier":
case "creator":
if (sortBy=="modified") tiddlers.reverse(); // show newest first
if (sortBy=="creator") { // sort by custom field with fallback value
tiddlers.sort(function (a,b) {
var v1=a.fields.creator||a.modifier;
var v2=b.fields.creator||b.modifier;
return (v1==v2)?0:(v1>v2?1:-1);
});
}
var lastSection = "";
for (var t = 0; t < tiddlers.length; t++){
var tiddler = tiddlers[t];
var theSection = "";
var m=tiddler.modified;
if (sortBy=="modified") theSection=m.getFullYear()+'.'+(m.getMonth()+1)+'.'+m.getDate();
if (sortBy=="modifier") theSection = tiddler.modifier;
if (sortBy=="creator") theSection=tiddler.fields['creator']||tiddler.modifier;
if (theSection != lastSection) {
lastSection = theSection;
if (sortBy=="modified") theSection = m.formatString(list.dateFormat);
list.options[i++] = new Option('+ '+theSection,"");
}
list.options[i++] = new Option(indent+indent+tiddler.title,tiddler.title);
}
expandTOC(list);
break;
case "tags":
// tagged tiddlers, by tag
var tagcount=0;
var lastTag = null;
for (var t = 0; t < tiddlers.length; t++) { // actually a list of tags, not tiddlers...
var theTag = tiddlers[t][0]; var tid=store.getTiddler(theTag);
if (tid && tid.isTagged('excludeLists')) continue; // skip excluded tags
var temp = store.getTaggedTiddlers(theTag);
var tagged=[]; for (var q=0; q<temp.length; q++) // hide excluded tiddlers
if (!temp[q].isTagged('excludeLists')) tagged.push(temp[q]);
if (tagged.length) { tagcount++;
list.options[i++]=new Option('+ '+theTag+" ("+tagged.length+")","");
for(var r=0; r<tagged.length; r++)
list.options[i++]=
new Option(indent+indent+tagged[r].title,tagged[r].title);
}
}
// count untagged tiddlers
var temp = store.getTiddlers("title");
var c=0; for (var r=0; r<temp.length;r++) if (!temp[r].tags.length) c++;
// create 'pseudo-tag' listing untagged tiddlers (if any)
if (c>0) {
list.options[i++] = new Option("+ untagged ("+c+")","");
for (var r=0; r<temp.length;r++) if (!temp[r].tags.length)
list.options[i++] = new
Option(indent+indent+temp[r].title,temp[r].title);
}
list.options[0].text=tagcount+' tags:';
expandTOC(list);
break;
case "missing": case "orphans": case "shadows":
for (var t = 0; t < tiddlers.length; t++)
list.options[i++] = new Option(tiddlers[t],tiddlers[t]);
break;
}
list.selectedIndex=selectedIndex; // select current control item
list.size = (list.autosize)?list.options.length:list.requestedSize;
}
// show/hide branch of TOCList based on current selection
function expandTOC(list) {
var selectedIndex = list.selectedIndex;
if (selectedIndex==-1) selectedIndex=0;
var sortBy = list.sortBy;
// don't collapse/expand list for alpha-sorted "flatlist" TOC contents
// or list control items
if ((sortBy=="title")||(sortBy=="missing")||(sortBy=="orphans")||(sortBy=="shadows")) return;
if ((selectedIndex>0)&&(selectedIndex<=list.cmdMax)) return;
// get current selected text/value and cache the
// complete list. Then clear the current list contents
var theText = list.options[selectedIndex].text;
var theValue = list.options[selectedIndex].value;
if (!list.saved) {
list.saved=new Array();
for (var i=0;i<list.length;i++) list.saved[i]=list.options[i];
}
while (list.length > 0) { list.options[0] = null; }
// put back heading items until item text matches current selected heading
var i=0;
for (var t=0; t<list.saved.length; t++) {
var opt=list.saved[t];
if (list.expandall||(opt.value=='')||(i<=list.cmdMax)) list.options[i++] = opt;
if (opt.text==theText) break;
}
selectedIndex=i-1; // this is the NEW index of the current selected heading
// put back items with value!='' until value==''
for ( t++; t<list.saved.length; t++) {
var opt=list.saved[t];
if (list.expandall||opt.value!='') list.options[i++] = opt;
if (opt.value=='') break;
}
// put back remaining items with value==''
for ( ; t<list.saved.length; t++) {
var opt=list.saved[t];
if (list.expandall||opt.value=='') list.options[i++] = opt;
}
list.selectedIndex = selectedIndex;
list.size = (list.autosize)?list.options.length:list.requestedSize;
}
// these functions process clicks on the 'control links' that are displayed above the listbox
function getTOCListFromButton(which) {
var list = null;
switch (which.id) {
case 'TOCMenu':
var theSiblings = which.parentNode.parentNode.parentNode.childNodes;
var thePlace=which.parentNode.parentNode.parentNode.parentNode.parentNode.id;
break;
case 'TOCSmaller': case 'TOCLarger': case 'TOCMaximize':
var theSiblings = which.parentNode.parentNode.childNodes;
var thePlace=which.parentNode.parentNode.parentNode.parentNode.id;
break;
}
for (var k=0; k<theSiblings.length; k++)
if (theSiblings[k].className=="TOCList") { list=theSiblings[k]; break; }
return list;
}
function onClickTOCMenu(which) {
var list=getTOCListFromButton(which); if (!list) return;
var opening = list.style.display=="none";
if(config.options.chkAnimate) anim.startAnimating(new Slider(list,opening,false,"none"));
else list.style.display = opening ? "block" : "none" ;
if (!list.noShowCookie) { config.options.chkTOCShow = opening; saveOptionCookie("chkTOCShow"); }
return(false);
}
function resizeTOC(which) {
var list=getTOCListFromButton(which); if (!list) return;
var size = list.size;
if (list.style.display=="none") // make sure list is visible
if(config.options.chkAnimate) anim.startAnimating(new Slider(list,true,false,"none"));
else list.style.display = "block" ;
switch (which.id) {
case 'TOCSmaller': // decrease current listbox size
if (list.autosize) { list.autosize=false; size=config.options.txtTOCListSize; }
if (size==1) break;
size -= 1; // shrink by one line
list.requestedSize = list.size = size;
break;
case 'TOCLarger': // increase current listbox size
if (list.autosize) { list.autosize=false; size=config.options.txtTOCListSize; }
if (size>=list.options.length) break;
size += 1; // grow by one line
list.requestedSize = list.size = size;
break;
case 'TOCMaximize': // toggle autosize
list.autosize = (list.size!=list.options.length);
list.size = (list.autosize)?list.options.length:list.requestedSize;
break;
}
if (!list.noSizeCookie && !list.autosize)
{ config.options.txtTOCListSize=size; saveOptionCookie("txtTOCListSize"); }
}
//}}}
|Name|TableOfContentsPluginInfo|
|Source|http://www.TiddlyTools.com/#TableOfContentsPlugin|
|Documentation|http://www.TiddlyTools.com/#TableOfContentsPluginInfo|
|Version|2.4.3|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|documentation for TableOfContentsPlugin|
When there are many tiddlers in a document, the standard 'tabbed list of tiddlers' in the right-hand sidebar can become very long, occupying a lot of page space and requiring a lot scrolling in order to locate and select a tiddler. This plugin replaces the standard tabs with a listbox/droplist control that uses a very small amount of page space, regardless of the number of tiddlers in the document.
!!!!!Usage
<<<
{{{
<<tableOfContents label:... sort:... date:... size:...
width:... padding:... margin:... prompt:... inline hidelist
-title -date -author -creator -tags -missing -orphans -shadows
}}}
*''label:text'' (default="contents")<br>the text that appears above the listbox.
*''sort:fieldtype''<br>sets the initial display order for items in the listbox. 'fieldtype' is one of: ''title, modified, modifier, creator, tags, missing, orphans,'' or ''shadows''.
*''date:format''<br>format for dates in listbox display, using TiddlyWiki date formatting (e.g. "DDD, MMM DD YYY")
*''size:nnn'' (default=1)<br>the initial number of lines to display in the listbox. If size=1, a droplist is created, otherwise a fixed-size listbox is created. You can use "size:0" or "size:auto" to display a varible-height listbox that automatically adjusts to fit the current list contents without scrolling.
*''width:...'' (default=100%)<br>the width of the listbox/droplist, using CSS units cm, px, em, or %. You can also use a ".TOCList" custom CSS class definition to override the built-in CSS declarations for the listbox.
*''padding:...''<br>sets listbox CSS padding style
*''margin:...''<br>sets listbox CSS margin style
*''prompt:...''<br>sets non-selectable prompt text that is displayed as the first line of the listbox //(note: this feature is not supported by the listbox control on all browsers)//. Let's you include a short text message (such as "select a tiddler"), even when displaying a compact single-line droplist.
*''inline''<br>By default, the listbox is rendered inside a {{{<div>}}} element. This keyword causes the plugin to use a {{{<span>}}} instead, allowing for more flexible 'inline' placement when embedded within other content.
*''hidelist''<br>when present, only the listbox label and size controls will be appear when first displayed. Clicking the label toggles the listbox display.
*''-title, -date, -author, -creator, -tags, -missing, -orphans, -shadows''<br>Omits the indicated list command item and corresponding listbox content.
Select (or double-click) a title from the listbox to open a tiddler, or select a 'command' items to set the order and type of tiddlers that are shown in the list:
*''[by title]''<br>displays all tiddlers in the document in alphanumeric order
*''[by date/author/creator/tags]''<br>displays indented sections, sorted accordingly, with headings (indicated by a '+') that can be expanded, one at a time, to view the list of tiddlers in that section. You can also ''shift-click'' on a section heading expand/collapse all sections at once.
*''[missing]''<br>displays tiddlers that have been referenced within the document but do not yet exist.
*''[orphans]''<br>displays tiddlers that do exist in the document but have not been referenced by a link from anywhere else within the document.
*''[shadows]''<br>displays special default/fallback tiddlers that are used by TiddlyWiki to configure built-in features and add-on macros/extensions.
The ''size of the listbox can be adjusted'' so you can view more (or less) tiddler titles at one time. Select ''[-]'' to reduce the size by one line, ''[+]'' to increase the size by one line, or ''[=]'' to autosize the list to fit the current contents (toggles on/off). //Note: If the listbox is reduced to a single line, it displayed as a droplist instead of a fixed-sized listbox.// You can ''show/hide the entire listbox'' by selecting the "contents" label that appears above the listbox.
<<<
!!!!!Configuration
<<option chkTOCShow>> display table of contents listbox
<<option chkTOCIncludeHidden>> include tiddlers tagged with <<tag excludeLists>> in listbox
listbox shows <<option txtTOCListSize>> lines, sorted by <<option txtTOCSortBy>>
!!!!!Parameters
<<<
<<<
!!!!!Examples
<<<
{{{<<tableOfContents "label:all tiddlers" sort:title width:40% size:1>>}}}
<<tableOfContents "label:all tiddlers" sort:title width:40% size:1>>
{{{<<tableOfContents "label:by date" sort:modified size:1 width:40%>>}}}
<<tableOfContents "label:by date" sort:modified size:1 width:40%>>
{{{<<tableOfContents "label:tagged tiddlers" sort:tags size:1 width:40%>>}}}
<<tableOfContents "label:tagged tiddlers" sort:tags size:1 width:40%>>
{{{<<tableOfContents "label:shadow tiddlers" sort:shadows size:1 width:40%>>}}}
<<tableOfContents "label:shadow tiddlers" sort:shadows size:1 width:40%>>
<<<
!!!!!Revisions
<<<
2008.04.09 2.4.3 restored config.options.chkTOCShow and onClickTOCMenu() handler
2008.04.07 2.4.2 added "Configuration" section and removed config.options.chkTOCShow and onClickTOCMenu() handler
2008.01.08 [*.*.*] plugin size reduction: documentation moved to ...Info tiddler
2007.12.25 2.4.1 code cleanup and performance improvements
2007.12.25 2.4.0 renamed 'system' section to 'shadows' (and no longer list plugins, etc. in that section). Also, added 'by creator' sort order (with fallback to 'modifier' if 'creator' custom field is undefined). Thanks to RA for suggestion and code tweaks.
2007.12.04 [*.*.*] update for TW2.3.0: replaced deprecated core functions, regexps, and macros
2007.03.22 2.3.2 in refreshTOCLists(), when sorting by date, use convertToLocalYYYYMMDDHHMM() instead of formatString() to compare dates for 'section headings' and only use formatString() when actually generating the section heading date display. Improves performance significantly for date sorted listbox, especially in documents with hundreds of tiddlers. Suggestion by AndreasHoefler.
2007.03.21 2.3.1 in refreshTOCLists(), only get list of 'select' elements, instead of scanning through all elements (saves significant time during refresh events. Suggestion by AndreasHoefler.
2006.11.27 2.3.0 added ability to omit sections from listbox via macro params (e.g., "-date -tags", etc.). Based on request from DavidWinfield.
2006.05.21 2.2.7 added onkeyup handling for enter key (=view selected tiddler, equivalent to double-click)
2006.02.14 2.2.6 FF1501 fix: add 'var r' and 'var k' to unintended global variable declarations in refreshTOCList() and getTOCListFromButton(). Thanks for report from AndreasHoefler.
2006.02.04 2.2.5 add 'var' to unintended global variable declarations to avoid FireFox 1.5.0.1 crash bug when assigning to globals
2005.12.21 2.2.2 in onClickTOCList() and onDblClickTOCList(), prevent mouse events from 'bubbling' up to other handlers
2005.10.30 2.2.1 in refreshTOCList(), fixed calculation of "showHidden" to check for 'readOnly' (i.e., "via HTTP") flag. Based on a report from LyallPearce
2005.10.30 2.2.0 hide tiddlers tagged with 'excludeLists' (with option to override, i.e., "include hidden tiddlers")
2005.10.09 2.1.0 combined documentation and code in a single tiddler
added click toggle for expand-all vs. show-one-branch
2005.08.07 2.0.0 major re-write to not use static ID values for listbox controls, so that multiple macro instances can exist without corrupting each other or the DOM. Moved HTML and CSS definitions into plugin code instead of using separate tiddlers. Added macro parameters for label, sort, date, size, width, hidelist and showtabs
2005.08.03 1.0.3 added "showtabs" optional parameter
2005.07.27 1.0.2 core update 1.2.29: custom overlayStyleSheet() replaced with new core setStylesheet(). Added show/hide toggle (click on 'contents' link)
2005.07.23 1.0.1 added parameter checks and corrected addNotification() usage
2005.07.20 1.0.0 Initial Release
<<<
/***
|Name|TaggedTemplateTweak+|
|@@Modified@@| AXS, 03/2011: to include support for DEFAULT_NEW_TEMPLATE and to use template field when provided|
|Source|http://www.TiddlyTools.com/#TaggedTemplateTweak|
|Documentation|http://www.TiddlyTools.com/#TaggedTemplateTweakInfo|
|Version|1.6.1|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|use alternative ViewTemplate/EditTemplate for specific tiddlers|
This plugin extends the core function, story.chooseTemplateForTiddler(), so that any given tiddler can be viewed and/or edited using alternatives to the standard tiddler templates.
!!!!!Documentation
*@@MODIFIED BY AXS: Defaults to DEFAULT_NEW_TEMPLATE for tiddlers that don't exist. This template must be defined somewhere in a tiddler tagged {{{systemConfig}}} with the lines:
**{{{config.tiddlerTemplates[#]="TemplateName";}}}
**{{{DEFAULT_NEW_TEMPLATE=#;}}}
**where "TemplateName" is the name of the tiddler with the corresponding template, and {{{#}}} is an integer of your choosing;
*also: added a few lines of code so that when the "template" field is defined in a tiddler this has the final say on which template to use. Need some error-handling for cases when the "template" field is defined, but the actual template doesn't exist.
*see [[TaggedTemplateTweakInfo]]
!!!!!Revisions
<<<
2009.09.02 [1.6.1] apply field-based template (if any) *before* tag-based template
| please see [[TaggedTemplateTweakInfo]] for previous revision details |
2007.06.11 [1.0.0] initial release
<<<
!!!!!Code
***/
//{{{
version.extensions.TaggedTemplateTweak= {major: 1, minor: 6, revision: 1, date: new Date(2009,9,2)};
if (!config.options.txtTemplateTweakFieldname)
config.options.txtTemplateTweakFieldname='template';
Story.prototype.taggedTemplate_chooseTemplateForTiddler = Story.prototype.chooseTemplateForTiddler
Story.prototype.chooseTemplateForTiddler = function(title,template)
{
// get core template and split into theme and template name
var coreTemplate=this.taggedTemplate_chooseTemplateForTiddler.apply(this,arguments);
// following 4 lines added by AXS, 03/2011: if the template is defined by the caller, then use that template! if the tiddler doesn't exist, use the default new template. if it exists, check its template field and use that template
// (note: no error-checking yet for cases when the template defined in the template field doesn't exist.
if(template) return coreTemplate;
var tiddler=store.getTiddler(title);
if (!tiddler) return config.tiddlerTemplates[DEFAULT_NEW_TEMPLATE]; // tiddler doesn't exist... use default new template
if(store.getValue(title,'template')) return store.getValue('NOTES','template'); // if "template" field is defined, use this template
var theme=""; var template=coreTemplate;
var parts=template.split(config.textPrimitives.sectionSeparator);
if (parts[1]) { theme=parts[0]; template=parts[1]; }
else theme=config.options.txtTheme||""; // if theme is not specified
theme+=config.textPrimitives.sectionSeparator;
// look for template using title as prefix
if (!store.getTaggedTiddlers(title).length) { // if tiddler is not a tag
if (store.getTiddlerText(theme+title+template))
{ return theme+title+template; } // theme##TitleTemplate
if (store.getTiddlerText(title+template))
{ return title+template; } // TitleTemplate
}
// look for templates using custom field value as prefix
var v=store.getValue(title,config.options.txtTemplateTweakFieldname);
if (store.getTiddlerText(theme+v+template))
{ return theme+v+template; } // theme##valueTemplate
if (store.getTiddlerText(v+template))
{ return v+template; } // valueTemplate
// look for template using tags as prefix
for (i=0; i<tiddler.tags.length; i++) {
var t=tiddler.tags[i]+template; // add tag prefix to template
var c=t.substr(0,1).toUpperCase()+t.substr(1); // capitalized for WikiWord title
if (store.getTiddlerText(theme+t)) { return theme+t; } // theme##tagTemplate
if (store.getTiddlerText(theme+c)) { return theme+c; } // theme##TagTemplate
if (store.getTiddlerText(t)) { return t; } // tagTemplate
if (store.getTiddlerText(c)) { return c; } // TagTemplate
}
// no match... use core result
return coreTemplate;
}
//}}}
/***
|Name|TaggedTemplateTweakInfo|
|Source|http://www.TiddlyTools.com/#TaggedTemplateTweak|
|Documentation|http://www.TiddlyTools.com/#TaggedTemplateTweakInfo|
|Version|1.6.1|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|documentation|
|Description|Documentation for TaggedTemplateTweak|
This plugin extends the core function, story.chooseTemplateForTiddler(), so that any given tiddler can be viewed and/or edited using alternatives to the standard tiddler templates. To select alternative templates, a 'template prefix' is determined by using the tiddler's title or matching a tag value or using a value stored in a custom tiddler field.
!!!!!Usage
<<<
*The plugin first attempts to use the tiddler's //title// as a prefix added to the standard TiddlyWiki template titles, [[ViewTemplate]] and [[EditTemplate]] (i.e., ''TiddlerNameViewTemplate'' and ''TiddlerNameEditTemplate''). This allows you to associate a custom template with a specific tiddler, without needing to add any special tags or custom field values to that individual tiddler.
*You can also define a tiddler's template prefix by using a //custom tiddler field// named 'template'. If no corresponding template was found using the tiddler's title, then the tiddler's 'template' field value, if present, will be used as a prefix (e.g., if template='SomeThing', then [[SomeThingViewTemplate]] will be applied).
*If no template is found using the either the title or 'template' field, then each of the tiddler's tags is tried as a template prefix, until a corresponding template, if any, is found. For example, any tiddlers that are tagged with ''<<tag media>>'' could find alternative templates named [[mediaViewTemplate]] and [[mediaEditTemplate]].
*If you using a systemTheme, the plugin will also tries adding the currently selected theme name (specified by {{{config.options.txtTheme}}}) to the template name (e.g. ''[[SomeTheme##MediaViewTemplate]]'') so that the alternative template definitions can be contained as //sections// within a single systemTheme tiddler.
*Lastly, if no alternative template is found at all, the standard [[ViewTemplate]] or [[EditTemplate]] definition as determined by the TiddlyWiki core handler is used.
Notes:
*You can redefine the //name// of the custom field used to store the template prefix. For example, to use the name of a TiddlyWeb server-side 'bag' as a prefix (so that tiddlers from separate bags can have different appearances), add the following to a tiddler tagged with<<tag systemConfig>>:{{block{
{{{
config.options.txtTemplateTweakFieldname='server.bag'; // use TiddlyWeb bag name as prefix
}}}
}}}
*To permit use of templates that have proper WikiWord tiddler titles (e.g., [[MediaViewTemplate]] and [[MediaEditTemplate]]), the plugin also attempts to use a capitalized form of the tag value (e.g., ''Media'') as a prefix. //This capitalization is for comparison purposes only and will not alter the actual tag values that are stored in the tiddler.//
<<<
!!!!!Examples
<<<
|Sample tiddler| tag | view template | edit template |
|[[MediaSample - QuickTime]]| <<tag media>> | [[MediaViewTemplate]] | [[MediaEditTemplate]] |
|[[MediaSample - Windows]]| <<tag media>> | [[MediaViewTemplate]] | [[MediaEditTemplate]] |
|[[CDSample]]| <<tag CD>> | [[CDViewTemplate]] | [[CDEditTemplate]] |
|<<newTiddler label:"create new task..." title:SampleTask tag:task text:"Type some text and then press DONE to view the task controls">> | <<tag task>> | [[TaskViewTemplate]] | [[EditTemplate]] |
//(note: if these samples are not present in your document, please visit// http://www.TiddlyTools.com/ //to view these sample tiddlers on-line)//
<<<
!!!!!Revisions
<<<
2009.09.02 1.6.1 apply field-based template (if any) *before* tag-based template
2009.07.31 1.6.0 added support for using custom field value as prefix
2009.05.04 1.5.2 check for tiddler exist *after* title-as-prefix (allows shadow tiddlers to use custom templates)
2009.01.06 1.5.1 reversed logic so that title-as-prefix takes precedence over tag-matched prefix
2008.12.18 1.5.0 added handling for using tiddler //title// as prefix (e.g., {{{SomeTiddlerViewTemplate}}})
2008.08.29 1.4.1 corrected handling for tiddlers with no matching tagged template when non-default theme is in effect (e.g., use "MyTheme##ViewTemplate").
2008.05.15 1.4.0 support use of *shadow* tagged templates (e.g., [[DiscussionViewTemplate]] created by [[DiscussionPlugin]])
2008.05.10 1.3.0 corrected handling for determining core template when using theme with sections
2008.05.01 1.2.5 added support for tagged templates stored as sections in a theme
2008.04.01 1.2.0 added support for using systemTheme section-based template definitions (requested by Phil Hawksworth)
2008.01.22 [*.*.*] plugin size reduction - documentation moved to [[TaggedTemplateTweakInfo]]
2007.06.23 1.1.0 re-written to use automatic 'tag prefix' search instead of hard coded check for each tag. Allows new custom tags to be used without requiring code changes to this plugin.
2007.06.11 1.0.0 initial release
<<<
/***
|''Name:''|TagsTreePlugin|
|''Description:''|Displays tags hierachy as a tree of tagged tiddlers.<br>Can be used to create dynamic outline navigation.|
|''Version:''|1.0.1|
|''Date:''|Jan 04,2008|
|''Source:''|http://visualtw.ouvaton.org/VisualTW.html|
|''Author:''|Pascal Collin|
|''License:''|[[BSD open source license|License]]|
|''~CoreVersion:''|2.1.0|
|''Browser:''|Firefox 2.0; InternetExplorer 6.0|
!Demo
On the plugin [[homepage|http://visualtw.ouvaton.org/VisualTW.html]] :
*Try to tag some <<newTiddler>> with a tag displayed in the menu and edit MainMenu.
*Look at some tags like [[Plugins]] or [[menu]].
!Installation
#import the plugin,
#save and reload,
#optionally, edit TagsTreeStyleSheet.
! Usage
{{{<<tagsTree>>}}} macro accepts the following //optional// parameters.
|!#|!parameter|!description|!by default|
|1|{{{root}}}|Uses {{{root}}} tag as tree root|- In a //tiddler// content or template : uses the tiddler as root tag.<br>- In the //page// content or template (by ex MainMenu) : displays all untagged tags.|
|2|{{{excludeTag}}}|Excludes all such tagged tiddlers from the tree|Uses default excludeLists tag|
|3|{{{level}}}|Expands nodes until level {{{level}}}.<br>Value {{{0}}} hides expand/collapse buttons.|Nodes are collapsed on first level|
|4|{{{depth}}}|Hierachy depth|6 levels depth (H1 to H6 header styles)|
|5|{{{sortField}}}|Alternate sort field. By example : "index".|Sorts tags and tiddlers alphabetically (on their title)|
|6|{{{labelField}}}|Alertnate label field. By example : "label".|Displays tiddler's title|
!Useful addons
*[[FieldsEditorPlugin]] : //create//, //edit//, //view// and //delete// commands in toolbar <<toolbar fields>>.
*[[TaggerPlugin]] : Provides a drop down listing current tiddler tags, and allowing toggling of tags.
!Advanced Users
You can change the global defaults for TagsTreePlugin, like default {{{level}}} value or level styles, by editing or overriding the first config.macros.tagsTree attributes below.
!Code
***/
//{{{
config.macros.tagsTree = {
expand : "+",
collapse : "–",
depth : 6,
level : 1,
sortField : "",
labelField : "",
styles : ["h1","h2","h3","h4","h5","h6"],
trees : {}
}
config.macros.tagsTree.handler = function(place,macroName,params,wikifier,paramString,tiddler)
{
var root = params[0] ? params[0] : (tiddler ? tiddler.title : null);
var excludeTag = params[1] ? params[1] : "excludeTagsTree";
var level = params[2] ? params[2] : config.macros.tagsTree.level;
var depth = params[3] ? params[3] : config.macros.tagsTree.depth;
var sortField = params[4] ? params[4] : config.macros.tagsTree.sortField;
var labelField = params[5] ? params[5] : config.macros.tagsTree.labelField;
var showButtons = (level>0);
var id = config.macros.tagsTree.getId(place);
if (config.macros.tagsTree.trees[id]==undefined) config.macros.tagsTree.trees[id]={};
config.macros.tagsTree.createSubTree(place,id,root,excludeTag,[],level>0 ? level : 1,depth, sortField, labelField,showButtons);
}
config.macros.tagsTree.createSubTree = function(place, id, root, excludeTag, ancestors, level, depth, sortField, labelField,showButtons){
var childNodes = root ? this.getChildNodes(root, ancestors) : this.getRootTags(excludeTag);
var isOpen = (level>0) || (!showButtons);
if (root && this.trees[id][root]!=undefined) isOpen = this.trees[id][root];
if (root && ancestors.length) {
var t = store.getTiddler(root);
if (childNodes.length && depth>0) {
var wrapper = createTiddlyElement(place , this.styles[Math.min(Math.max(ancestors.length,1),6)-1],null,"branch");
if (showButtons) {
b = createTiddlyButton(wrapper, isOpen ? config.macros.tagsTree.collapse : config.macros.tagsTree.expand, null, config.macros.tagsTree.onClick);
b.setAttribute("treeId",id);
b.setAttribute("tiddler",root);
}
createTiddlyText(createTiddlyLink(wrapper, root),t&&labelField ? t.fields[labelField] ? t.fields[labelField] : root : root);
}
else
createTiddlyText(createTiddlyLink(place, root,false,"leaf"),t&&labelField ? t.fields[labelField] ? t.fields[labelField] : root : root);
}
if (childNodes.length && depth) {
var d = createTiddlyElement(place,"div",null,"subtree");
d.style.display= isOpen ? "block" : "none";
if (sortField)
childNodes.sort(function(a, b){
var fa=a.fields[sortField];
var fb=b.fields[sortField];
return (fa==undefined && fb==undefined) ? a.title < b.title ? -1 : a.title > b.title ? 1 : 0 : (fa==undefined && fb!=undefined) ? 1 :(fa!=undefined && fb==undefined) ? -1 : fa < fb ? -1 : fa > fb ? 1 : 0;
})
for (var cpt=0; cpt<childNodes.length; cpt++)
this.createSubTree(d, id, childNodes[cpt].title, excludeTag, ancestors.concat(root), level-1, depth-1, sortField, labelField, showButtons);
}
}
config.macros.tagsTree.onClick = function(e){
var id = this.getAttribute("treeId");
var tiddler = this.getAttribute("tiddler");
var n = this.parentNode.nextSibling;
var isOpen = n.style.display != "none";
if(config.options.chkAnimate && anim && typeof Slider == "function")
anim.startAnimating(new Slider(n,!isOpen,null,"none"));
else
n.style.display = isOpen ? "none" : "block";
this.firstChild.nodeValue = isOpen ? config.macros.tagsTree.expand : config.macros.tagsTree.collapse;
config.macros.tagsTree.trees[id][tiddler]=!isOpen;
return false;
}
config.macros.tagsTree.getChildNodes = function(root ,ancestors){
var childs = store.getTaggedTiddlers(root);
var result = new Array();
for (var cpt=0; cpt<childs.length; cpt++)
if (childs[cpt].title!=root && ancestors.indexOf(childs[cpt].title)==-1) result.push(childs[cpt]);
return result;
}
config.macros.tagsTree.getRootTags = function(excludeTag){
var tags = store.getTags(excludeTag);
tags.sort(function(a,b) {return a[0].toLowerCase() < b[0].toLowerCase() ? -1 : (a[0].toLowerCase() == b[0].toLowerCase() ? 0 : +1);});
var result = new Array();
for (var cpt=0; cpt<tags.length; cpt++) {
var t = store.getTiddler(tags[cpt][0]);
if (!t || t.tags.length==0) result.push(t ? t : {title:tags[cpt][0],fields:{}});
}
return result;
}
config.macros.tagsTree.getId = function(element){
while (!element.id && element.parentNode) element=element.parentNode;
return element.id ? element.id : "<html>";
}
config.shadowTiddlers.TagsTreeStyleSheet = "/*{{{*/\n";
config.shadowTiddlers.TagsTreeStyleSheet +=".leaf, .subtree {display:block; margin-left : 0.5em}\n";
config.shadowTiddlers.TagsTreeStyleSheet +=".subtree {margin-bottom:0.5em}\n";
config.shadowTiddlers.TagsTreeStyleSheet +="#mainMenu {text-align:left}\n";
config.shadowTiddlers.TagsTreeStyleSheet +=".branch .button {border:1px solid #DDD; color:#AAA;font-size:9px;padding:0 2px;margin-right:0.3em;vertical-align:middle;text-align:center;}\n";
config.shadowTiddlers.TagsTreeStyleSheet +="/*}}}*/";
store.addNotification("TagsTreeStyleSheet", refreshStyles);
config.shadowTiddlers.MainMenu="<<tagsTree>>"
config.shadowTiddlers.PageTemplate = config.shadowTiddlers.PageTemplate.replace(/id='mainMenu' refresh='content' /,"id='mainMenu' refresh='content' force='true' ")
//}}}
/***
|Name|TemporaryTiddlersPlugin|
|Source|http://www.TiddlyTools.com/#TemporaryTiddlersPlugin|
|Version|1.1.2|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|blocks tiddlers tagged with "temporary" from being saved into the TW file|
!!!!!Usage
<<<
When the TW document is saved (either to local disk or remote URL), any tiddlers tagged with "temporary" will be skipped over, so that they are not written to the file. To keep a temporary tiddler, simply edit it and remove the tag before saving the file. This feature can be combined with various plugins that can automatically create new tiddlers, such as [[SearchOptionsPlugin]] ([[SearchResults]]) and [[ImportTiddlersPlugin]] ([[ImportedTiddlers]]) so that these transient results are not retained when you save you document.
You can also use this tag with the {{{<<loadTiddlers>>}}} macro and the //auto-tagging// features provided by [[ImportTiddlersPlugin]], so that each time you open your document, you can automatically retrieve an up-to-date set of common tiddlers that are stored in another document (either local or via remote URL), without those tiddlers being retained when you save your document.
<<<
!!!!!Configuration
<<<
When saving the document:
<<option chkTemporaryQuiet>> Suppress reporting of individual temporary tiddlers that have not been saved
<<option chkTemporaryKeep>> Keep temporary tiddlers (i.e., ignore the 'temporary' tag)
Enter a tag value to use when marking tiddlers as temporary: <<option txtTemporaryTag>>
<<<
!!!!!Revisions
<<<
2008.11.14 [1.1.2] added "nnn temporary tiddlers not saved" summary message
2008.04.08 [1.1.1] don't automatically add configuration options to AdvancedOptions tiddler
2008.03.01 [1.1.0] added support for recognizing 'temporary' flag stored as a tiddler *field* (as an optional alternative to using a tag)
2007.02.08 [1.0.0] initial release
<<<
!!!!!Code
***/
//{{{
version.extensions.TemporaryTiddlersPlugin= {major: 1, minor: 1, revision: 2, date: new Date(2008,11,14)};
// configuration defaults
if (config.options.chkTemporaryKeep ==undefined) config.options.chkTemporaryKeep =false;
if (config.options.chkTemporaryQuiet==undefined) config.options.chkTemporaryQuiet=true;
if (config.options.txtTemporaryTag==undefined) config.options.txtTemporaryTag="temporary";
// lingo
config.messages.TemporaryWarning = "'%0' ...temporary tiddler";
config.messages.TemporarySummary = "%0 temporary tiddlers will not be saved";
// core override
SaverBase.prototype.externalize = function(store)
{
var results=[]; var totaltemps=0;
var tiddlers=store.getTiddlers("title");
for (var t=0; t<tiddlers.length; t++) {
if (config.options.chkTemporaryKeep||!(tiddlers[t].fields['temporary']||tiddlers[t].isTagged(config.options.txtTemporaryTag)))
results.push(this.externalizeTiddler(store, tiddlers[t]));
else {
if (!config.options.chkTemporaryQuiet) // notify user that tiddler won't be saved
displayMessage(config.messages.TemporaryWarning.format([tiddlers[t].title]));
totaltemps++;
}
}
if (totaltemps) displayMessage(config.messages.TemporarySummary.format([totaltemps]));
return results.join("\n");
}
//}}}
/***
|Name|TiddlerTweakerPlugin|
|Source|http://www.TiddlyTools.com/#TiddlerTweakerPlugin|
|Version|2.4.5|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|select multiple tiddlers and modify author, created, modified and/or tag values|
~TiddlerTweaker is a 'power tool' for TiddlyWiki authors. Select multiple tiddlers from a listbox and 'bulk modify' the creator, author, created, modified and/or tag values of those tiddlers using a compact set of form fields. The values you enter into the fields simultaneously overwrite the existing values in all tiddlers you have selected.
!!!!!Usage
<<<
{{{<<tiddlerTweaker>>}}}
{{smallform{<<tiddlerTweaker>>}}}
By default, any tags you enter into the TiddlerTweaker will //replace// the existing tags in all the tiddlers you have selected. However, you can also use TiddlerTweaker to quickly filter specified tags from the selected tiddlers, while leaving any other tags assigned to those tiddlers unchanged:
>Any tag preceded by a '+' (plus) or '-' (minus), will be added or removed from the existing tags //instead of replacing the entire tag definition// of each tiddler (e.g., enter '-excludeLists' to remove that tag from all selected tiddlers. When using this syntax, care should be taken to ensure that //every// tag is preceded by '+' or '-', to avoid inadvertently overwriting any other existing tags on the selected tiddlers. (note: the '+' or '-' prefix on each tag value is NOT part of the tag value, and is only used by TiddlerTweaker to control how that tag value is processed)
Important Notes:
* TiddlerTweaker is a 'power user' tool that can make changes to many tiddlers at once. ''You should always have a recent backup of your document (or 'save changes' just *before* tweaking the tiddlers), just in case you accidentally 'shoot yourself in the foot'.''
* The date and author information on any tiddlers you tweak will ONLY be updated if the corresponding checkboxes have been selected. As a general rule, after using TiddlerTweaker, always ''//remember to save your document//'' when you are done, even though the tiddler timeline tab may not show any recently modified tiddlers.
* Selecting and updating all tiddlers in a document can take a while. Your browser may warn about an 'unresponsive script'. Usually, if you allow it to continue, it should complete the processing... eventually. Nonetheless, be sure to save your work before you begin tweaking lots of tiddlers, just in case something does get stuck.
<<<
!!!!!Revisions
<<<
2011.01.21 2.4.5 auto-selection: use "-" for untagged tiddlers. Also, added 'opened', 'invert'
2009.09.15 2.4.4 added 'edit' button. moved html definition to separate section
2009.09.13 2.4.3 in settiddlers(), convert backslashed chars (\n\b\s\t) in replacement text
2009.06.26 2.4.2 only add brackets around tags containing spaces
2009.06.22 2.4.1 in setFields(), add brackets around all tags shown tweaker edit field
2009.03.30 2.4.0 added 'sort by modifier'
2009.01.22 2.3.0 added support for text pattern find/replace
2008.10.27 2.2.3 in setTiddlers(), fixed Safari bug by replacing static Array.concat(...) with new Array().concat(...)
2008.09.07 2.2.2 added removeCookie() function for compatibility with [[CookieManagerPlugin]]
2008.05.12 2.2.1 replace built-in backstage tweak task with tiddler tweaker control panel (moved from BackstageTweaks)
2008.01.13 2.2.0 added 'auto-selection' links: all, changed, tags, title, text
2007.12.26 2.1.0 added support for managing 'creator' custom field (see [[CoreTweaks]])
2007.11.01 2.0.3 added config.options.txtTweakerSortBy for cookie-based persistence of list display order preference setting.
2007.09.28 2.0.2 in settiddlers() and deltiddlers(), added suspend/resume notification handling (improves performance when operating on multiple tiddlers)
2007.08.03 2.0.1 added shadow definition for [[TiddlerTweaker]] tiddler for use as parameter references with {{{<<tiddler>>, <<slider>> or <<tabs>>}}} macros.
2007.08.03 2.0.0 converted from inline script
2006.01.01 1.0.0 initial release
<<<
!!!!!Code
***/
//{{{
version.extensions.TiddlerTweakerPlugin= {major: 2, minor: 4, revision: 5, date: new Date(2011,1,21)};
// shadow tiddler
config.shadowTiddlers.TiddlerTweaker='<<tiddlerTweaker>>';
// defaults
if (config.options.txtTweakerSortBy==undefined) config.options.txtTweakerSortBy='modified';
// backstage task
if (config.tasks) { // for TW2.2b3 or above
config.tasks.tweak.tooltip='review/modify tiddler internals: dates, authors, tags, etc.';
config.tasks.tweak.content='{{smallform small groupbox{<<tiddlerTweaker>>}}}';
}
// if removeCookie() function is not defined by TW core, define it here.
if (window.removeCookie===undefined) {
window.removeCookie=function(name) {
document.cookie = name+'=; expires=Thu, 01-Jan-1970 00:00:01 UTC; path=/;';
}
}
config.macros.tiddlerTweaker = {
handler: function(place,macroName,params,wikifier,paramString,tiddler) {
var span=createTiddlyElement(place,'span');
span.innerHTML=store.getTiddlerText('TiddlerTweakerPlugin##html');
this.init(span.getElementsByTagName('form')[0],config.options.txtTweakerSortBy);
},
init: function(f,sortby) { // set form controls
if (!f) return; // form might not be rendered yet...
while (f.list.options[0]) f.list.options[0]=null; // empty the list
var tids=store.getTiddlers(sortby);
if (sortby=='size') // descending order
tids.sort(function(a,b) {return a.text.length > b.text.length ? -1 : (a.text.length == b.text.length ? 0 : +1);});
var who='';
for (i=0; i<tids.length; i++) { var t=tids[i];
var label=t.title; var value=t.title;
switch (sortby) {
case 'modified':
case 'created':
var t=tids[tids.length-i-1]; // reverse order
var when=t[sortby].formatString('YY.0MM.0DD 0hh:0mm ');
label=when+t.title;
value=t.title;
break;
case 'size':
label='['+t.text.length+'] '+label;
break;
case 'modifier':
case 'creator':
if (who!=t[sortby]) {
who=t[sortby];
f.list.options[f.list.length]=new Option('by '+who+':','',false,false);
}
label='\xa0\xa0\xa0'+label; // indent
break;
}
f.list.options[f.list.length]=new Option(label,value,false,false);
}
f.title.value=f.who.value=f.creator.value=f.tags.value='';
f.cm.value=f.cd.value=f.cy.value=f.ch.value=f.cn.value='';
f.mm.value=f.md.value=f.my.value=f.mh.value=f.mn.value='';
f.stats.disabled=f.set.disabled=f.del.disabled=f.edit.disabled=f.display.disabled=true;
f.settitle.disabled=false;
config.options.txtTweakerSortBy=sortby;
f.sortby.value=sortby; // sync droplist
if (sortby!='modified') saveOptionCookie('txtTweakerSortBy');
else removeCookie('txtTweakerSortBy');
},
enablefields: function(here) { // enables/disables inputs based on #items selected
var f=here.form; var list=f.list;
var c=0; for (i=0;i<list.length;i++) if (list.options[i].selected) c++;
if (c>1) f.title.disabled=true;
if (c>1) f.settitle.checked=false;
f.set.disabled=(c==0);
f.del.disabled=(c==0);
f.edit.disabled=(c==0);
f.display.disabled=(c==0);
f.settitle.disabled=(c>1);
f.stats.disabled=(c==0);
var msg=(c==0)?'select tiddlers':(c+' tiddler'+(c!=1?'s':'')+' selected');
here.previousSibling.firstChild.firstChild.nextSibling.innerHTML=msg;
if (c) clearMessage(); else displayMessage('no tiddlers selected');
},
setfields: function(here) { // set fields from first selected tiddler
var f=here.form;
if (!here.value.length) {
f.title.value=f.who.value=f.creator.value=f.tags.value='';
f.cm.value=f.cd.value=f.cy.value=f.ch.value=f.cn.value='';
f.mm.value=f.md.value=f.my.value=f.mh.value=f.mn.value='';
return;
}
var tid=store.getTiddler(here.value); if (!tid) return;
f.title.value=tid.title;
f.who.value=tid.modifier;
f.creator.value=tid.fields['creator']||''; // custom field - might not exist
f.tags.value=tid.tags.map(function(t){return String.encodeTiddlyLink(t)}).join(' ');
var c=tid.created; var m=tid.modified;
f.cm.value=c.getMonth()+1;
f.cd.value=c.getDate();
f.cy.value=c.getFullYear();
f.ch.value=c.getHours();
f.cn.value=c.getMinutes();
f.mm.value=m.getMonth()+1;
f.md.value=m.getDate();
f.my.value=m.getFullYear();
f.mh.value=m.getHours();
f.mn.value=m.getMinutes();
},
selecttiddlers: function(here,callback) {
var f=here; while (f&&f.nodeName.toLowerCase()!='form')f=f.parentNode;
for (var t=f.list.options.length-1; t>=0; t--)
f.list.options[t].selected=callback(f.list.options[t]);
config.macros.tiddlerTweaker.enablefields(f.list);
return false;
},
settiddlers: function(here) {
var f=here.form; var list=f.list;
var tids=[];
for (i=0;i<list.length;i++) if (list.options[i].selected) tids.push(list.options[i].value);
if (!tids.length) { alert('please select at least one tiddler'); return; }
var cdate=new Date(f.cy.value,f.cm.value-1,f.cd.value,f.ch.value,f.cn.value);
var mdate=new Date(f.my.value,f.mm.value-1,f.md.value,f.mh.value,f.mn.value);
if (tids.length>1 && !confirm('Are you sure you want to update these tiddlers:\n\n'+tids.join(', '))) return;
store.suspendNotifications();
for (t=0;t<tids.length;t++) {
var tid=store.getTiddler(tids[t]); if (!tid) continue;
var title=!f.settitle.checked?tid.title:f.title.value;
var who=!f.setwho.checked?tid.modifier:f.who.value;
var text=tid.text;
if (f.replacetext.checked) {
var r=f.replacement.value.replace(/\\t/mg,'\t').unescapeLineBreaks();
text=text.replace(new RegExp(f.pattern.value,'mg'),r);
}
var tags=tid.tags;
if (f.settags.checked) {
var intags=f.tags.value.readBracketedList();
var addtags=[]; var deltags=[]; var reptags=[];
for (i=0;i<intags.length;i++) {
if (intags[i].substr(0,1)=='+')
addtags.push(intags[i].substr(1));
else if (intags[i].substr(0,1)=='-')
deltags.push(intags[i].substr(1));
else
reptags.push(intags[i]);
}
if (reptags.length)
tags=reptags;
if (addtags.length)
tags=new Array().concat(tags,addtags);
if (deltags.length)
for (i=0;i<deltags.length;i++)
{ var pos=tags.indexOf(deltags[i]); if (pos!=-1) tags.splice(pos,1); }
}
if (!f.setcdate.checked) cdate=tid.created;
if (!f.setmdate.checked) mdate=tid.modified;
store.saveTiddler(tid.title,title,text,who,mdate,tags,tid.fields);
if (f.setcreator.checked) store.setValue(tid.title,'creator',f.creator.value); // set creator
if (f.setcdate.checked) tid.assign(null,null,null,null,null,cdate); // set create date
}
store.resumeNotifications();
this.init(f,f.sortby.value);
},
displaytiddlers: function(here,edit) {
var f=here.form; var list=f.list;
var tids=[];
for (i=0; i<list.length;i++) if (list.options[i].selected) tids.push(list.options[i].value);
if (!tids.length) { alert('please select at least one tiddler'); return; }
story.displayTiddlers(story.findContainingTiddler(f),tids,edit?DEFAULT_EDIT_TEMPLATE:null);
},
deltiddlers: function(here) {
var f=here.form; var list=f.list;
var tids=[];
for (i=0;i<list.length;i++) if (list.options[i].selected) tids.push(list.options[i].value);
if (!tids.length) { alert('please select at least one tiddler'); return; }
if (!confirm('Are you sure you want to delete these tiddlers:\n\n'+tids.join(', '))) return;
store.suspendNotifications();
for (t=0;t<tids.length;t++) {
var tid=store.getTiddler(tids[t]); if (!tid) continue;
if (tid.tags.contains('systemConfig')) {
var msg=tid.title+' is tagged with systemConfig.'
+'\n\nRemoving this tiddler may cause unexpected results. Are you sure?';
if (!confirm(msg)) continue;
}
store.removeTiddler(tid.title);
story.closeTiddler(tid.title);
}
store.resumeNotifications();
this.init(f,f.sortby.value);
},
stats: function(here) {
var f=here.form; var list=f.list; var tids=[]; var out=''; var tot=0;
var target=f.nextSibling;
for (i=0;i<list.length;i++) if (list.options[i].selected) tids.push(list.options[i].value);
if (!tids.length) { alert('please select at least one tiddler'); return; }
for (t=0;t<tids.length;t++) {
var tid=store.getTiddler(tids[t]); if (!tid) continue;
out+='[['+tid.title+']] '+tid.text.length+'\n'; tot+=tid.text.length;
}
var avg=tot/tids.length;
out=tot+' bytes in '+tids.length+' selected tiddlers ('+avg+' bytes/tiddler)\n<<<\n'+out+'<<<\n';
removeChildren(target);
target.innerHTML="<hr><font size=-2><a href='javascript:;' style='float:right' "
+"onclick='this.parentNode.parentNode.style.display=\"none\"'>close</a></font>";
wikify(out,target);
target.style.display='block';
}
};
//}}}
/***
//{{{
!html
<style>
.tiddlerTweaker table,
.tiddlerTweaker table tr,
.tiddlerTweaker table td
{ padding:0;margin:0;border:0;white-space:nowrap; }
</style><form class='tiddlerTweaker'><!--
--><table style="width:100%"><tr valign="top"><!--
--><td style="text-align:center;width:99%;"><!--
--><font size=-2><div style="text-align:left;"><span style="float:right"><!--
--> <a href="javascript:;"
title="select all tiddlers"
onclick="return config.macros.tiddlerTweaker.selecttiddlers(this,function(opt){
return opt.value.length;
});">all</a><!--
--> <a href="javascript:;"
title="select tiddlers currently displayed in the story column"
onclick="return config.macros.tiddlerTweaker.selecttiddlers(this,function(opt){
return story.getTiddler(opt.value);
});">opened</a><!--
--> <a href="javascript:;"
title="select tiddlers that are new/changed since the last file save"
onclick="var lastmod=new Date(document.lastModified);
return config.macros.tiddlerTweaker.selecttiddlers(this,function(opt){
var tid=store.getTiddler(opt.value);
return tid&&tid.modified>lastmod;
});
">changed</a><!--
--> <a href="javascript:;"
title="select tiddlers with at least one matching tag"
onclick="var t=prompt('Enter space-separated tags (match one or more). Use \x22-\x22 to match untagged tiddlers');
if (!t||!t.length) return false;
var tags=t.readBracketedList();
return config.macros.tiddlerTweaker.selecttiddlers(this,function(opt){
var tid=store.getTiddler(opt.value);
return tid&&tags[0]=='-'?!tid.tags.length:tid.tags.containsAny(tags);
});
">tags</a><!--
--> <a href="javascript:;"
title="select tiddlers whose titles include matching text"
onclick="var t=prompt('Enter a title (or portion of a title) to match');
if (!t||!t.length) return false;
return config.macros.tiddlerTweaker.selecttiddlers(this,function(opt){
return opt.value.indexOf(t)!=-1;
});
">titles</a><!--
--> <a href="javascript:;"
title="select tiddlers containing matching text"
onclick="var t=prompt('Enter tiddler text (content) to match');
if (!t||!t.length) return false;
return config.macros.tiddlerTweaker.selecttiddlers(this,function(opt){
var tt=store.getTiddlerText(opt.value,'');
return tt.indexOf(t)!=-1;
});
">text</a><!--
--> <a href="javascript:;"
title="reverse selection of all list items"
onclick="return config.macros.tiddlerTweaker.selecttiddlers(this,function(opt){
return !opt.selected;
});">invert</a><!--
--></span><span>select tiddlers</span><!--
--></div><!--
--></font><select multiple name=list size="11" style="width:99.99%"
title="use click, shift-click and/or ctrl-click to select multiple tiddler titles"
onclick="config.macros.tiddlerTweaker.enablefields(this)"
onchange="config.macros.tiddlerTweaker.setfields(this)"><!--
--></select><br><!--
-->show<input type=text size=1 value="11"
onchange="this.form.list.size=this.value; this.form.list.multiple=(this.value>1);"><!--
-->by<!--
--><select name=sortby size=1
onchange="config.macros.tiddlerTweaker.init(this.form,this.value)"><!--
--><option value="title">title</option><!--
--><option value="size">size</option><!--
--><option value="modified">modified</option><!--
--><option value="created">created</option><!--
--><option value="modifier">modifier</option><!--
--></select><!--
--><input type="button" value="refresh"
onclick="config.macros.tiddlerTweaker.init(this.form,this.form.sortby.value)"<!--
--> <input type="button" name="stats" disabled value="totals..."
onclick="config.macros.tiddlerTweaker.stats(this)"><!--
--></td><td style="width:1%"><!--
--><div style="text-align:left"><font size=-2> modify values</font></div><!--
--><table style="width:100%;"><tr><!--
--><td style="padding:1px"><!--
--><input type=checkbox name=settitle unchecked
title="allow changes to tiddler title (rename tiddler)"
onclick="this.form.title.disabled=!this.checked">title<!--
--></td><td style="padding:1px"><!--
--><input type=text name=title size=35 style="width:98%" disabled><!--
--></td></tr><tr><td style="padding:1px"><!--
--><input type=checkbox name=setcreator unchecked
title="allow changes to tiddler creator"
onclick="this.form.creator.disabled=!this.checked">created by<!--
--></td><td style="padding:1px;"><!--
--><input type=text name=creator size=35 style="width:98%" disabled><!--
--></td></tr><tr><td style="padding:1px"><!--
--><input type=checkbox name=setwho unchecked
title="allow changes to tiddler author"
onclick="this.form.who.disabled=!this.checked">modified by<!--
--></td><td style="padding:1px"><!--
--><input type=text name=who size=35 style="width:98%" disabled><!--
--></td></tr><tr><td style="padding:1px"><!--
--><input type=checkbox name=setcdate unchecked
title="allow changes to created date"
onclick="var f=this.form;
f.cm.disabled=f.cd.disabled=f.cy.disabled=f.ch.disabled=f.cn.disabled=!this.checked"><!--
-->created on<!--
--></td><td style="padding:1px"><!--
--><input type=text name=cm size=2 style="width:2em;padding:0;text-align:center" disabled><!--
--> / <input type=text name=cd size=2 style="width:2em;padding:0;text-align:center" disabled><!--
--> / <input type=text name=cy size=4 style="width:3em;padding:0;text-align:center" disabled><!--
--> at <input type=text name=ch size=2 style="width:2em;padding:0;text-align:center" disabled><!--
--> : <input type=text name=cn size=2 style="width:2em;padding:0;text-align:center" disabled><!--
--></td></tr><tr><td style="padding:1px"><!--
--><input type=checkbox name=setmdate unchecked
title="allow changes to modified date"
onclick="var f=this.form;
f.mm.disabled=f.md.disabled=f.my.disabled=f.mh.disabled=f.mn.disabled=!this.checked"><!--
-->modified on<!--
--></td><td style="padding:1px"><!--
--><input type=text name=mm size=2 style="width:2em;padding:0;text-align:center" disabled><!--
--> / <input type=text name=md size=2 style="width:2em;padding:0;text-align:center" disabled><!--
--> / <input type=text name=my size=4 style="width:3em;padding:0;text-align:center" disabled><!--
--> at <input type=text name=mh size=2 style="width:2em;padding:0;text-align:center" disabled><!--
--> : <input type=text name=mn size=2 style="width:2em;padding:0;text-align:center" disabled><!--
--></td></tr><tr><td style="padding:1px"><!--
--><input type=checkbox name=replacetext unchecked
title="find/replace matching text"
onclick="this.form.pattern.disabled=this.form.replacement.disabled=!this.checked">replace text<!--
--></td><td style="padding:1px"><!--
--><input type=text name=pattern size=15 value="" style="width:40%" disabled
title="enter TEXT PATTERN (regular expression)"> with<!--
--><input type=text name=replacement size=15 value="" style="width:40%" disabled
title="enter REPLACEMENT TEXT"><!--
--></td></tr><tr><td style="padding:1px"><!--
--><input type=checkbox name=settags checked
title="allow changes to tiddler tags"
onclick="this.form.tags.disabled=!this.checked">tags<!--
--></td><td style="padding:1px"><!--
--><input type=text name=tags size=35 value="" style="width:98%"
title="enter new tags or use '+tag' and '-tag' to add/remove tags from existing tags"><!--
--></td></tr></table><!--
--><div style="text-align:center"><!--
--><nobr><input type=button name=display disabled style="width:24%" value="display"
title="show selected tiddlers"
onclick="config.macros.tiddlerTweaker.displaytiddlers(this,false)"><!--
--> <input type=button name=edit disabled style="width:23%" value="edit"
title="edit selected tiddlers"
onclick="config.macros.tiddlerTweaker.displaytiddlers(this,true)"><!--
--> <input type=button name=del disabled style="width:24%" value="delete"
title="remove selected tiddlers"
onclick="config.macros.tiddlerTweaker.deltiddlers(this)"><!--
--> <input type=button name=set disabled style="width:24%" value="update"
title="update selected tiddlers"
onclick="config.macros.tiddlerTweaker.settiddlers(this)"></nobr><!--
--></div><!--
--></td></tr></table><!--
--></form><span style="display:none"><!--content replaced by tiddler "stats"--></span>
!end
//}}}
***/
*Double-click on a collapsed section to expand it
*Click on section title and drag to rearrange sections
*The {{{view}}} menu shows all open sections
*To enable edit mode, click {{button{edit mode}}} in the {{{options}}} menu
*To increase text size, use the {{{font size}}} options in the the {{{options}}} menu
*Use {{button{link}}} (in the toolbar) and {{button{permaview}}} (in the {{{options}}} menu) to create different permanent links to book content
*See [[Annotating]] for tips on editing content and adding notes
/%
!info
|Name|ToggleRightSidebar|
|Source|http://www.TiddlyTools.com/#ToggleRightSidebar|
|Version|2.0.0|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|transclusion|
|Description|show/hide right sidebar (SideBarOptions)|
Usage
<<<
{{{
<<tiddler ToggleRightSidebar>>
<<tiddler ToggleRightSidebar with: label tooltip>>
}}}
Try it: <<tiddler ToggleRightSidebar##show
with: {{config.options.chkShowRightSidebar?'►':'◄'}}>>
<<<
Configuration:
<<<
copy/paste the following settings into a tiddler tagged with <<tag systemConfig>> and then modify the values to suit your preferences:
{{{
config.options.chkShowRightSidebar=false;
config.options.txtToggleRightSideBarLabelShow="◄";
config.options.txtToggleRightSideBarLabelHide="►";
}}}
<<<
!end
!show
<<tiddler {{
var co=config.options;
if (co.chkShowRightSidebar===undefined) co.chkShowRightSidebar=true;
var sb=document.getElementById('sidebar');
var da=document.getElementById('displayArea');
if (sb) {
sb.style.display=co.chkShowRightSidebar?'block':'none';
da.style.marginRight=co.chkShowRightSidebar?'':'1em';
}
'';}}>><html><nowiki><a href='javascript:;' title="$2"
onmouseover="
this.href='javascript:void(eval(decodeURIComponent(%22(function(){try{('
+encodeURIComponent(encodeURIComponent(this.onclick))
+')()}catch(e){alert(e.description?e.description:e.toString())}})()%22)))';"
onclick="
var co=config.options;
var opt='chkShowRightSidebar';
var show=co[opt]=!co[opt];
var sb=document.getElementById('sidebar');
var da=document.getElementById('displayArea');
if (sb) {
sb.style.display=show?'block':'none';
da.style.marginRight=show?'':'1em';
}
saveOptionCookie(opt);
var labelShow=co.txtToggleRightSideBarLabelShow||'◄';
var labelHide=co.txtToggleRightSideBarLabelHide||'►';
if (this.innerHTML==labelShow||this.innerHTML==labelHide)
this.innerHTML=show?labelHide:labelShow;
this.title=(show?'hide':'show')+' right sidebar';
var sm=document.getElementById('storyMenu');
if (sm) config.refreshers.content(sm);
return false;
">$1</a></html>
!end
%/<<tiddler {{
var src='ToggleRightSidebar';
src+(tiddler&&tiddler.title==src?'##info':'##show');
}} with: {{
var co=config.options;
var labelShow=co.txtToggleRightSideBarLabelShow||'◄';
var labelHide=co.txtToggleRightSideBarLabelHide||'►';
'$1'!='$'+'1'?'$1':(co.chkShowRightSidebar?labelHide:labelShow);
}} {{
var tip=(config.options.chkShowRightSidebar?'hide':'show')+' right sidebar';
'$2'!='$'+'2'?'$2':tip;
}}>>
/***
|Name|ToggleSideBarMacro|
|Created by|SaqImtiaz|
|Location|http://tw.lewcid.org/#ToggleSideBarMacro|
|Version|1.0|
|Requires|~TW2.x|
!Description:
Provides a button for toggling visibility of the SideBar. You can choose whether the SideBar should initially be hidden or displayed.
!Demo
<<toggleSideBar "Toggle Sidebar">>
!Usage:
{{{<<toggleSideBar>>}}} <<toggleSideBar>>
additional options:
{{{<<toggleSideBar label tooltip show/hide>>}}} where:
label = custom label for the button,
tooltip = custom tooltip for the button,
show/hide = use one or the other, determines whether the sidebar is shown at first or not.
(default is to show the sidebar)
You can add it to your tiddler toolbar, your MainMenu, or where you like really.
If you are using a horizontal MainMenu and want the button to be right aligned, put the following in your StyleSheet:
{{{ .HideSideBarButton {float:right;} }}}
!History
*23-07-06: version 1.0: completely rewritten, now works with custom stylesheets too, and easier to customize start behaviour.
*20-07-06: version 0.11
*27-04-06: version 0.1: working.
!Code
***/
//{{{
config.macros.toggleSideBar={};
config.macros.toggleSideBar.settings={
styleHide : "#sidebar { display: none;}\n"+"#contentWrapper #displayArea { margin-right: 1em;}\n"+"",
styleShow : " ",
arrow1: "«",
arrow2: "»"
};
config.macros.toggleSideBar.handler=function (place,macroName,params,wikifier,paramString,tiddler)
{
var tooltip= params[1]||'toggle sidebar';
var mode = (params[2] && params[2]=="hide")? "hide":"show";
var arrow = (mode == "hide")? this.settings.arrow1:this.settings.arrow2;
var label= (params[0]&¶ms[0]!='.')?params[0]+" "+arrow:arrow;
var theBtn = createTiddlyButton(place,label,tooltip,this.onToggleSideBar,"button HideSideBarButton");
if (mode == "hide")
{
(document.getElementById("sidebar")).setAttribute("toggle","hide");
setStylesheet(this.settings.styleHide,"ToggleSideBarStyles");
}
};
config.macros.toggleSideBar.onToggleSideBar = function(){
var sidebar = document.getElementById("sidebar");
var settings = config.macros.toggleSideBar.settings;
if (sidebar.getAttribute("toggle")=='hide')
{
setStylesheet(settings.styleShow,"ToggleSideBarStyles");
sidebar.setAttribute("toggle","show");
this.firstChild.data= (this.firstChild.data).replace(settings.arrow1,settings.arrow2);
}
else
{
setStylesheet(settings.styleHide,"ToggleSideBarStyles");
sidebar.setAttribute("toggle","hide");
this.firstChild.data= (this.firstChild.data).replace(settings.arrow2,settings.arrow1);
}
return false;
}
setStylesheet(".HideSideBarButton .button {font-weight:bold; padding: 0 5px;}\n","ToggleSideBarButtonStyles");
//}}}
|~ViewToolbar|permalink snapshotPrintHere collapseOthers closeOthers collapseTiddler closeTiddler|
|~EditOptions|easyEdit reload|
|~AdminOptions|fields references editHtml editTiddler|
|~EditToolbar|saveTiddler -cancelTiddler|
|~adminViewToolbar|permalink snapshotPrintHere collapseOthers closeOthers collapseTiddler closeTiddler > fields references|
|~adminViewToolbarEditMode|easyEdit reload permalink snapshotPrintHere collapseOthers closeOthers collapseTiddler closeTiddler > fields references editHtml editTiddler|
|~adminEditToolbar|saveTiddler -cancelTiddler deleteTiddler|
|~userViewToolbar|permalink snapshotPrintHere collapseOthers closeOthers collapseTiddler closeTiddler|
|~userViewToolbarEditMode|easyEdit reload permalink snapshotPrintHere collapseOthers closeOthers collapseTiddler closeTiddler|
|~userEditToolbar|saveTiddler -cancelTiddler|
|~CollapsedToolbar|closeOthers +expandTiddler closeTiddler|
|~NotesToolbar|easyEditNote permalink snapshotPrintHere collapseOthers closeOthers collapseTiddler closeTiddler|
| tiddlyspot password:|<<option pasUploadPassword>>|
| site management:|<<upload http://goljanpathology.tiddlyspot.com/store.cgi index.html . . goljanpathology>>//(requires tiddlyspot password)//<br>[[control panel|http://goljanpathology.tiddlyspot.com/controlpanel]], [[download (go offline)|http://goljanpathology.tiddlyspot.com/download]]|
| links:|[[tiddlyspot.com|http://tiddlyspot.com/]], [[FAQs|http://faq.tiddlyspot.com/]], [[blog|http://tiddlyspot.blogspot.com/]], email [[support|mailto:support@tiddlyspot.com]] & [[feedback|mailto:feedback@tiddlyspot.com]], [[donate|http://tiddlyspot.com/?page=donate]]|
/***
Description: Contains the stuff you need to use Tiddlyspot
Note, you also need UploadPlugin, PasswordOptionPlugin and LoadRemoteFileThroughProxy
from http://tiddlywiki.bidix.info for a complete working Tiddlyspot site.
***/
//{{{
// edit this if you are migrating sites or retrofitting an existing TW
config.tiddlyspotSiteId = 'goljanpathology';
// make it so you can by default see edit controls via http
config.options.chkHttpReadOnly = false;
window.readOnly = false; // make sure of it (for tw 2.2)
window.showBackstage = true; // show backstage too
// disable autosave in d3
if (window.location.protocol != "file:")
config.options.chkGTDLazyAutoSave = false;
// tweak shadow tiddlers to add upload button, password entry box etc
with (config.shadowTiddlers) {
SiteUrl = 'http://'+config.tiddlyspotSiteId+'.tiddlyspot.com';
SideBarOptions = SideBarOptions.replace(/(<<saveChanges>>)/,"$1<<tiddler TspotSidebar>>");
OptionsPanel = OptionsPanel.replace(/^/,"<<tiddler TspotOptions>>");
DefaultTiddlers = DefaultTiddlers.replace(/^/,"[[WelcomeToTiddlyspot]] ");
MainMenu = MainMenu.replace(/^/,"[[WelcomeToTiddlyspot]] ");
}
// create some shadow tiddler content
merge(config.shadowTiddlers,{
'TspotOptions':[
"tiddlyspot password:",
"<<option pasUploadPassword>>",
""
].join("\n"),
'TspotControls':[
"| tiddlyspot password:|<<option pasUploadPassword>>|",
"| site management:|<<upload http://" + config.tiddlyspotSiteId + ".tiddlyspot.com/store.cgi index.html . . " + config.tiddlyspotSiteId + ">>//(requires tiddlyspot password)//<br>[[control panel|http://" + config.tiddlyspotSiteId + ".tiddlyspot.com/controlpanel]], [[download (go offline)|http://" + config.tiddlyspotSiteId + ".tiddlyspot.com/download]]|",
"| links:|[[tiddlyspot.com|http://tiddlyspot.com/]], [[FAQs|http://faq.tiddlyspot.com/]], [[blog|http://tiddlyspot.blogspot.com/]], email [[support|mailto:support@tiddlyspot.com]] & [[feedback|mailto:feedback@tiddlyspot.com]], [[donate|http://tiddlyspot.com/?page=donate]]|"
].join("\n"),
'WelcomeToTiddlyspot':[
"This document is a ~TiddlyWiki from tiddlyspot.com. A ~TiddlyWiki is an electronic notebook that is great for managing todo lists, personal information, and all sorts of things.",
"",
"@@font-weight:bold;font-size:1.3em;color:#444; //What now?// @@ Before you can save any changes, you need to enter your password in the form below. Then configure privacy and other site settings at your [[control panel|http://" + config.tiddlyspotSiteId + ".tiddlyspot.com/controlpanel]] (your control panel username is //" + config.tiddlyspotSiteId + "//).",
"<<tiddler TspotControls>>",
"See also GettingStarted.",
"",
"@@font-weight:bold;font-size:1.3em;color:#444; //Working online// @@ You can edit this ~TiddlyWiki right now, and save your changes using the \"save to web\" button in the column on the right.",
"",
"@@font-weight:bold;font-size:1.3em;color:#444; //Working offline// @@ A fully functioning copy of this ~TiddlyWiki can be saved onto your hard drive or USB stick. You can make changes and save them locally without being connected to the Internet. When you're ready to sync up again, just click \"upload\" and your ~TiddlyWiki will be saved back to tiddlyspot.com.",
"",
"@@font-weight:bold;font-size:1.3em;color:#444; //Help!// @@ Find out more about ~TiddlyWiki at [[TiddlyWiki.com|http://tiddlywiki.com]]. Also visit [[TiddlyWiki.org|http://tiddlywiki.org]] for documentation on learning and using ~TiddlyWiki. New users are especially welcome on the [[TiddlyWiki mailing list|http://groups.google.com/group/TiddlyWiki]], which is an excellent place to ask questions and get help. If you have a tiddlyspot related problem email [[tiddlyspot support|mailto:support@tiddlyspot.com]].",
"",
"@@font-weight:bold;font-size:1.3em;color:#444; //Enjoy :)// @@ We hope you like using your tiddlyspot.com site. Please email [[feedback@tiddlyspot.com|mailto:feedback@tiddlyspot.com]] with any comments or suggestions."
].join("\n"),
'TspotSidebar':[
"<<upload http://" + config.tiddlyspotSiteId + ".tiddlyspot.com/store.cgi index.html . . " + config.tiddlyspotSiteId + ">><html><a href='http://" + config.tiddlyspotSiteId + ".tiddlyspot.com/download' class='button'>download</a></html>"
].join("\n")
});
//}}}
<<upload http://goljanpathology.tiddlyspot.com/store.cgi index.html . . goljanpathology>><html><a href='http://goljanpathology.tiddlyspot.com/download' class='button'>download</a></html>
/***
|Name|UnsavedChanges+Plugin|
|Source|http://www.TiddlyTools.com/#UnsavedChangesPlugin|
|Version|3.3.4|
|Author|Eric Shulman|
|License|http://www.TiddlyTools.com/#LegalStatements|
|~CoreVersion|2.1|
|Type|plugin|
|Description|show droplist of tiddlers that have changed since the last time the document was saved|
Display a list of tiddlers that have been changed since the last time the document was saved. The list includes all new/modified tiddlers as well as those changed with "minor edits" enabled and any tiddlers that you import during the session, regardless of their modification date.
!!!!!Usage
<<<
{{{
<<unsavedChanges panel>> or <<unsavedChanges>>
}}}
{{indent{
the ''panel'' keyword displays a 'control panel' interface containing a droplist of unsaved tiddlers and a 'goto' button, along with a command link to 'save changes'. Depending upon what other plugins are installed, several additional elements will also be displayed: When [[NestedSlidersPlugin]] is installed, the entire control panel is contained within a ''SLIDER''. When [[LoadTiddlersPlugin]] is installed, a ''REVERT'' button is added. When [[SaveAsPlugin]] is installed, a ''SAVE AS'' link is added. When [[UploadPlugin]] is installed, an ''UPLOAD'' (or ''save to web'') link is added. When [[TrashPlugin]] is installed and there are tiddlers tagged with<<tag Trash>>, an ''EMPTY TRASH'' link is added.
}}}
{{{
<<unsavedChanges list separator>>
}}}
{{indent{
the ''list'' keyword displays a simple space-separated list of unsaved tiddlers without any other command links. You can specify an optional ''separator'' value that can be used in place of the default space character. For example, you can specify {{{"<br>"}}} as the separator in order to display each link, one per line.
}}}
{{{
<<unsavedChanges command label tip>>
}}}
{{indent{
the ''command'' keyword displays a single 'command link' that, when clicked, displays a ~TiddlyWiki popup containing the list of unsaved tiddlers, the 'save changes' command and, depending upon what other plugins are installed, additional commands for 'save as', 'upload', and 'empty trash' (similar to the panel display described above).
You can specify optional ''label'' and ''tip'' parameters in the macro to customize the command link text and tooltip. The default label for the command link is: "There %1 %0 unsaved tiddler%2...", where:
* %0 is automatically replaced with the number of unsaved changes
* %1 is either "is" (if changes=1) or "are" (if changes>1)
* %2 is either blank (if changes=1) or "s" (if changes>1)
resulting in the text: //"there is 1 unsaved tiddler...", "There are 2 unsaved tiddlers...", etc.//
}}}
<<<
!!!!!Examples
<<<
^^//note: the following examples will not display any output unless you have already created/modified tiddlers in the current document.//^^
{{{<<unsavedChanges>>}}}
<<unsavedChanges>>
----
{{{<<unsavedChanges command>>}}}
<<unsavedChanges command>>
----
{{{<<unsavedChanges list>>}}}
<<unsavedChanges list>>
----
{{{<<unsavedChanges list "<br>">>}}}
<<unsavedChanges list "<br>">>
<<<
!!!!!Revisions
<<<
2010.12.05 3.3.4 display 'save as...' command even if readOnly
2009.03.02 3.3.3 fix handling for titles that contain HTML special chars (lt,gt,quot,amp)
2008.09.02 3.3.2 cleanup popup list output generation and added timestamps/sizes to popup display
2008.08.23 3.3.1 added optional custom 'label' and 'tip' params to 'command' mode and defined default values for mode, label, tip, and separator as object properties for I18N/L10N-readiness.
2008.08.21 3.3.0 complete re-write of rendering and refresh processing to support multiple instances and automatic self-refresh (no longer depends upon core refresh notifications)
2008.08.21 3.2.0 added 'command' option for link+popup as alternative to 'control panel' interface
2008.04.22 3.1.2 use SaveAsPlugin instead of obsolete NewDocumentPlugin to add "save as" link
2007.12.22 3.1.1 hijack removeTiddler() instead of low-level deleteTiddler() to correct tracking and refresh handling issues. in saveTiddler(), check for 'tiddler rename' (title!=newtitle) and adjust list accordingly.
2007.12.21 3.1.0 added support for {{{<<unsavedChanges list separator>>}}} usage to unsaved tiddlers as a simple list of links, embedded in tiddler content (e.g., [[MainMenu]])
2007.12.20 3.0.0 rewrite to track ALL changed tiddlers, including imports and minor edits, regardless of saved modification dates. Also, rewrote display logic to directly refresh macro output instead of triggering a page refresh. The entire process is MUCH more efficient now.
2007.08.02 2.0.0 converted from inline script
2007.01.01 1.0.0 initial release
<<<
!!!!!Code
***/
//{{{
version.extensions.UnsavedChangesPlugin= {major: 3, minor: 3, revision: 4, date: new Date(2010,12,5)};
config.macros.unsavedChanges = {
changed: [], // list of currently unsaved tiddler titles
defMode: "panel",
defSep: " ",
defLabel: "There %1 %0 unsaved tiddler%2",
defTip: "view a list of unsaved tiddler changes",
handler: function(place,macroName,params,wikifier,paramString,tiddler) {
var wrapper=createTiddlyElement(place,"span",null,"unsavedChanges");
wrapper.setAttribute("mode",params[0]||this.defMode);
wrapper.setAttribute("sep",params[1]||this.defSep); // for 'list' mode
wrapper.setAttribute("label",params[1]||this.defLabel); // for 'command' mode
wrapper.setAttribute("tip",params[2]||this.defTip); // for 'command' mode
this.render(wrapper);
},
render: function(wrapper) {
removeChildren(wrapper); // make sure its empty
if (!this.changed.length) return; // no changes = no output
switch (wrapper.getAttribute("mode")) {
case "command": this.command(wrapper); break;
case "list": this.list(wrapper); break;
case "panel": default: this.panel(wrapper); break;
}
},
refresh: function() {
var wrappers=document.getElementsByTagName("span");
for (var w=0; w<wrappers.length; w++)
if (hasClass(wrappers[w],"unsavedChanges"))
this.render(wrappers[w]);
},
list: function(place) { // show simple list of unsaved tiddlers
wikify("[["+this.changed.join("]]"+place.getAttribute("sep")+"[[")+"]]",place);
},
command: function(place) { // show command link with popup list
var c=this.changed.length;
var txt=place.getAttribute("label").format([c,c==1?'is':'are',c==1?'':'s']);
var tip=place.getAttribute("tip");
var action=function(ev) { if (!ev) var ev=window.event;
var p=Popup.create(this); if (!p) return false;
var d=createTiddlyElement(p,"div");
d.style.whiteSpace="normal"; d.style.width="auto"; d.style.padding="2px";
// gather pretty links for changed tiddlers
var list=[]; var item=" [[%1 - %0 (%2 bytes)|%0]] ";
for (var i=config.macros.unsavedChanges.changed.length-1; i>=0; i--) {
var tid=store.getTiddler(config.macros.unsavedChanges.changed[i]);
if (!tid) continue;
var when=tid.modified.formatString('YYYY.0MM.0DD 0hh:0mm:0ss');
list.push(item.format([tid.title,when,tid.text.length]));
}
wikify("@@white-space:nowrap;"+list.join("<br>")+"@@",d);
var t="\n----\n";
t+="@@white-space:nowrap;display:block;text-align:center; ";
if (!readOnly) {
t+="<<saveChanges>>";
t+=config.macros.saveAs?" | <<saveAs>>":"";
t+=config.macros.upload?" | <<upload>>":"";
t+=(config.macros.emptyTrash&&store.getTaggedTiddlers("Trash").length)?" | <<emptyTrash>>":"";
} else {
t+=config.macros.saveAs?"<<saveAs>>":"";
}
t+=" @@";
wikify(t,d);
Popup.show();
ev.cancelBubble=true; if(ev.stopPropagation)ev.stopPropagation();
return(false);
}
createTiddlyButton(place,txt,tip,action,"button");
},
panel: function(place) { // show composite droplist+buttons+commands
// gather changed tiddlers (in reverse order by date - most recent first)
var tids=[]; for (var i=this.changed.length-1; i>=0; i--)
{ var t=store.getTiddler(this.changed[i]); if (t) tids.push(t); }
tids.sort(function(a,b){return a.modified<b.modified?-1:(a.modified==b.modified?0:1);});
// generate droplist items
var list=[]; var item='<option value="%0">%1 - %0 (%2 bytes)</option>';
for (var i=tids.length-1; i>=0; i--) {
var when=tids[i].modified.formatString('YYYY.0MM.0DD 0hh:0mm:0ss');
list.push(item.format([tids[i].title.htmlEncode(),when,tids[i].text.length]));
}
// display droplist, buttons, and command links
var out=''; var c=this.changed.length;
var NSP=config.formatters.findByField("name","nestedSliders");
var summary=this.defLabel.format([c,c==1?'is':'are',c==1?'':'s'])
out+=NSP?'+++(unsaved)['+summary+'|'+this.defTip+']...':(summary+"\n");
out+='<html><form style="display:inline"><!--\
--><select size="1" name="list" \
title="select a tiddler to view" \
onchange="var v=this.value; if (v.length) story.displayTiddler(null,v);"><!--\
-->'+list.join('')+'<!--\
--></select><!--\
--><input type="button" value="goto" onclick="this.form.list.onchange();">';
if (config.macros.loadTiddlers) {
out+='<input type="button" value="revert" \
title="import the last saved version of this tiddler" \
onclick="var v=this.form.list.value; if (!v.length) return; \
var t=\'<\'+\'<loadTiddlers [[tiddler:\'+v+\']] \'; \
t+=document.location.href; \
t+=\' confirm force noreport>\'+\'>\'; \
var e=document.getElementById(\'executeRevert\'); \
if (e) e.parentNode.removeChild(e); \
e=document.createElement(\'span\'); \
e.id=\'executeRevert\'; \
wikify(t,e);">';
}
out+='</form></html>';
out+='\n{{small nowrap{';
if (!readOnly) {
out+="<<saveChanges>>";
out+=config.macros.saveAs?" | <<saveAs>>":"";
out+=config.macros.upload?" | <<upload>>":"";
out+=(config.macros.emptyTrash&&store.getTaggedTiddlers("Trash").length)?" | <<emptyTrash>>":"";
} else {
out+=config.macros.saveAs?"<<saveAs>>":"";
}
out+='}}}';
out+=NSP?'===':'';
wikify(out,place);
}
};
// hijack store.saveTiddler() to track changes to tiddlers
if (store.showUnsaved_saveTiddler==undefined) {
store.showUnsaved_saveTiddler=store.saveTiddler;
store.saveTiddler=function(title,newtitle) {
if (title!=newtitle) {
var i=config.macros.unsavedChanges.changed.indexOf(title);
if (i!=-1) config.macros.unsavedChanges.changed.splice(i,1); // remove old from list
}
var i=config.macros.unsavedChanges.changed.indexOf(newtitle);
if (i!=-1) config.macros.unsavedChanges.changed.splice(i,1); // remove new title from list
config.macros.unsavedChanges.changed.push(newtitle); // add new title to END of list
var t=this.showUnsaved_saveTiddler.apply(this,arguments);
if (!this.notificationLevel) config.macros.unsavedChanges.refresh();
return t;
}
}
// hijack store.removeTiddler() to track changes to tiddlers
if (store.showUnsaved_removeTiddler==undefined) {
store.showUnsaved_removeTiddler=store.removeTiddler;
store.removeTiddler=function(title) {
var i=config.macros.unsavedChanges.changed.indexOf(title);
if (i!=-1) config.macros.unsavedChanges.changed.splice(i,1); // remove from list
this.showUnsaved_removeTiddler.apply(this,arguments);
if (!this.notificationLevel) config.macros.unsavedChanges.refresh();
}
}
// hijack store.setDirty() function to reset change list after file save
// note: do NOT hijack the prototype function. This hijack should only be applied to
// the main 'store' instance only (i.e., don't refresh when loading temporary store
// as part of ImportTiddlers processing)
if (store.showUnsaved_setDirty==undefined) {
store.showUnsaved_setDirty=store.setDirty;
store.setDirty = function(flag) {
var refresh=this.isDirty() && !flag; // 'dirty' to 'clean', force a refresh...
this.showUnsaved_setDirty.apply(this,arguments); // but change the flag first.
if (refresh) {
config.macros.unsavedChanges.changed=[]; // clear changed list
config.macros.unsavedChanges.refresh();
}
}
}
//}}}
| !date | !user | !location | !storeUrl | !uploadDir | !toFilename | !backupdir | !origin |
| 17/03/2011 18:24:00 | user | [[2010GoljanPathology_TiddlyWiki.html|file:///Users/AS/Sites/SCmobile/2010GoljanPathology_TiddlyWiki.html]] | [[store.cgi|http://goljanpathology.tiddlyspot.com/store.cgi]] | . | [[index.html | http://goljanpathology.tiddlyspot.com/index.html]] | . | ok |
| 18/03/2011 01:44:00 | user | [[2010GoljanPathology_TiddlyWiki.html|file:///Users/AS/Sites/SCmobile/2010GoljanPathology_TiddlyWiki.html]] | [[store.cgi|http://goljanpathology.tiddlyspot.com/store.cgi]] | . | [[index.html | http://goljanpathology.tiddlyspot.com/index.html]] | . |
| 18/03/2011 02:02:09 | user | [[2010GoljanPathology_TiddlyWiki.html|file:///Users/AS/Sites/SCmobile/2010GoljanPathology_TiddlyWiki.html]] | [[store.cgi|http://goljanpathology.tiddlyspot.com/store.cgi]] | . | [[index.html | http://goljanpathology.tiddlyspot.com/index.html]] | . | ok |
| 18/03/2011 02:10:27 | user | [[2010GoljanPathology_TiddlyWiki.html|file:///Users/AS/Sites/SCmobile/2010GoljanPathology_TiddlyWiki.html]] | [[store.cgi|http://goljanpathology.tiddlyspot.com/store.cgi]] | . | [[index.html | http://goljanpathology.tiddlyspot.com/index.html]] | . | ok |
| 28/03/2011 00:34:58 | admin | [[2010GoljanPathology_TiddlyWiki.html|file:///Users/AS/Sites/SCmobile/2010GoljanPathology_TiddlyWiki.html]] | [[store.cgi|http://goljanpathology.tiddlyspot.com/store.cgi]] | . | [[index.html | http://goljanpathology.tiddlyspot.com/index.html]] | . |
| 24/05/2011 17:49:42 | admin | [[/|http://goljanpathology.tiddlyspot.com/#Chapters]] | [[store.cgi|http://goljanpathology.tiddlyspot.com/store.cgi]] | . | [[index.html | http://goljanpathology.tiddlyspot.com/index.html]] | . |
| 24/05/2011 18:42:05 | admin | [[/|http://goljanpathology.tiddlyspot.com/#Contents]] | [[store.cgi|http://goljanpathology.tiddlyspot.com/store.cgi]] | . | [[index.html | http://goljanpathology.tiddlyspot.com/index.html]] | . |
| 24/05/2011 18:43:53 | admin | [[/|http://goljanpathology.tiddlyspot.com/#Contents]] | [[store.cgi|http://goljanpathology.tiddlyspot.com/store.cgi]] | . | [[index.html | http://goljanpathology.tiddlyspot.com/index.html]] | . |
| 24/05/2011 18:43:55 | admin | [[/|http://goljanpathology.tiddlyspot.com/#Contents]] | [[store.cgi|http://goljanpathology.tiddlyspot.com/store.cgi]] | . | [[index.html | http://goljanpathology.tiddlyspot.com/index.html]] | . |
| 10/09/2011 12:59:40 | admin | [[/|http://goljanpathology.tiddlyspot.com/]] | [[store.cgi|http://goljanpathology.tiddlyspot.com/store.cgi]] | . | [[index.html | http://goljanpathology.tiddlyspot.com/index.html]] | . |
/***
|''Name:''|UploadPlugin|
|''Description:''|Save to web a TiddlyWiki|
|''Version:''|4.1.3|
|''Date:''|Feb 24, 2008|
|''Source:''|http://tiddlywiki.bidix.info/#UploadPlugin|
|''Documentation:''|http://tiddlywiki.bidix.info/#UploadPluginDoc|
|''Author:''|BidiX (BidiX (at) bidix (dot) info)|
|''License:''|[[BSD open source license|http://tiddlywiki.bidix.info/#%5B%5BBSD%20open%20source%20license%5D%5D ]]|
|''~CoreVersion:''|2.2.0|
|''Requires:''|PasswordOptionPlugin|
***/
//{{{
version.extensions.UploadPlugin = {
major: 4, minor: 1, revision: 3,
date: new Date("Feb 24, 2008"),
source: 'http://tiddlywiki.bidix.info/#UploadPlugin',
author: 'BidiX (BidiX (at) bidix (dot) info',
coreVersion: '2.2.0'
};
//
// Environment
//
if (!window.bidix) window.bidix = {}; // bidix namespace
bidix.debugMode = false; // true to activate both in Plugin and UploadService
//
// Upload Macro
//
config.macros.upload = {
// default values
defaultBackupDir: '', //no backup
defaultStoreScript: "store.php",
defaultToFilename: "index.html",
defaultUploadDir: ".",
authenticateUser: true // UploadService Authenticate User
};
config.macros.upload.label = {
promptOption: "Save and Upload this TiddlyWiki with UploadOptions",
promptParamMacro: "Save and Upload this TiddlyWiki in %0",
saveLabel: "save to web",
saveToDisk: "save to disk",
uploadLabel: "upload"
};
config.macros.upload.messages = {
noStoreUrl: "No store URL in parmeters or options",
usernameOrPasswordMissing: "Username or password missing"
};
config.macros.upload.handler = function(place,macroName,params) {
if (readOnly)
return;
var label;
if (document.location.toString().substr(0,4) == "http")
label = this.label.saveLabel;
else
label = this.label.uploadLabel;
var prompt;
if (params[0]) {
prompt = this.label.promptParamMacro.toString().format([this.destFile(params[0],
(params[1] ? params[1]:bidix.basename(window.location.toString())), params[3])]);
} else {
prompt = this.label.promptOption;
}
createTiddlyButton(place, label, prompt, function() {config.macros.upload.action(params);}, null, null, this.accessKey);
};
config.macros.upload.action = function(params)
{
// for missing macro parameter set value from options
if (!params) params = {};
var storeUrl = params[0] ? params[0] : config.options.txtUploadStoreUrl;
var toFilename = params[1] ? params[1] : config.options.txtUploadFilename;
var backupDir = params[2] ? params[2] : config.options.txtUploadBackupDir;
var uploadDir = params[3] ? params[3] : config.options.txtUploadDir;
var username = params[4] ? params[4] : config.options.txtUploadUserName;
var password = config.options.pasUploadPassword; // for security reason no password as macro parameter
// for still missing parameter set default value
if ((!storeUrl) && (document.location.toString().substr(0,4) == "http"))
storeUrl = bidix.dirname(document.location.toString())+'/'+config.macros.upload.defaultStoreScript;
if (storeUrl.substr(0,4) != "http")
storeUrl = bidix.dirname(document.location.toString()) +'/'+ storeUrl;
if (!toFilename)
toFilename = bidix.basename(window.location.toString());
if (!toFilename)
toFilename = config.macros.upload.defaultToFilename;
if (!uploadDir)
uploadDir = config.macros.upload.defaultUploadDir;
if (!backupDir)
backupDir = config.macros.upload.defaultBackupDir;
// report error if still missing
if (!storeUrl) {
alert(config.macros.upload.messages.noStoreUrl);
clearMessage();
return false;
}
if (config.macros.upload.authenticateUser && (!username || !password)) {
alert(config.macros.upload.messages.usernameOrPasswordMissing);
clearMessage();
return false;
}
bidix.upload.uploadChanges(false,null,storeUrl, toFilename, uploadDir, backupDir, username, password);
return false;
};
config.macros.upload.destFile = function(storeUrl, toFilename, uploadDir)
{
if (!storeUrl)
return null;
var dest = bidix.dirname(storeUrl);
if (uploadDir && uploadDir != '.')
dest = dest + '/' + uploadDir;
dest = dest + '/' + toFilename;
return dest;
};
//
// uploadOptions Macro
//
config.macros.uploadOptions = {
handler: function(place,macroName,params) {
var wizard = new Wizard();
wizard.createWizard(place,this.wizardTitle);
wizard.addStep(this.step1Title,this.step1Html);
var markList = wizard.getElement("markList");
var listWrapper = document.createElement("div");
markList.parentNode.insertBefore(listWrapper,markList);
wizard.setValue("listWrapper",listWrapper);
this.refreshOptions(listWrapper,false);
var uploadCaption;
if (document.location.toString().substr(0,4) == "http")
uploadCaption = config.macros.upload.label.saveLabel;
else
uploadCaption = config.macros.upload.label.uploadLabel;
wizard.setButtons([
{caption: uploadCaption, tooltip: config.macros.upload.label.promptOption,
onClick: config.macros.upload.action},
{caption: this.cancelButton, tooltip: this.cancelButtonPrompt, onClick: this.onCancel}
]);
},
options: [
"txtUploadUserName",
"pasUploadPassword",
"txtUploadStoreUrl",
"txtUploadDir",
"txtUploadFilename",
"txtUploadBackupDir",
"chkUploadLog",
"txtUploadLogMaxLine"
],
refreshOptions: function(listWrapper) {
var opts = [];
for(i=0; i<this.options.length; i++) {
var opt = {};
opts.push();
opt.option = "";
n = this.options[i];
opt.name = n;
opt.lowlight = !config.optionsDesc[n];
opt.description = opt.lowlight ? this.unknownDescription : config.optionsDesc[n];
opts.push(opt);
}
var listview = ListView.create(listWrapper,opts,this.listViewTemplate);
for(n=0; n<opts.length; n++) {
var type = opts[n].name.substr(0,3);
var h = config.macros.option.types[type];
if (h && h.create) {
h.create(opts[n].colElements['option'],type,opts[n].name,opts[n].name,"no");
}
}
},
onCancel: function(e)
{
backstage.switchTab(null);
return false;
},
wizardTitle: "Upload with options",
step1Title: "These options are saved in cookies in your browser",
step1Html: "<input type='hidden' name='markList'></input><br>",
cancelButton: "Cancel",
cancelButtonPrompt: "Cancel prompt",
listViewTemplate: {
columns: [
{name: 'Description', field: 'description', title: "Description", type: 'WikiText'},
{name: 'Option', field: 'option', title: "Option", type: 'String'},
{name: 'Name', field: 'name', title: "Name", type: 'String'}
],
rowClasses: [
{className: 'lowlight', field: 'lowlight'}
]}
};
//
// upload functions
//
if (!bidix.upload) bidix.upload = {};
if (!bidix.upload.messages) bidix.upload.messages = {
//from saving
invalidFileError: "The original file '%0' does not appear to be a valid TiddlyWiki",
backupSaved: "Backup saved",
backupFailed: "Failed to upload backup file",
rssSaved: "RSS feed uploaded",
rssFailed: "Failed to upload RSS feed file",
emptySaved: "Empty template uploaded",
emptyFailed: "Failed to upload empty template file",
mainSaved: "Main TiddlyWiki file uploaded",
mainFailed: "Failed to upload main TiddlyWiki file. Your changes have not been saved",
//specific upload
loadOriginalHttpPostError: "Can't get original file",
aboutToSaveOnHttpPost: 'About to upload on %0 ...',
storePhpNotFound: "The store script '%0' was not found."
};
bidix.upload.uploadChanges = function(onlyIfDirty,tiddlers,storeUrl,toFilename,uploadDir,backupDir,username,password)
{
var callback = function(status,uploadParams,original,url,xhr) {
if (!status) {
displayMessage(bidix.upload.messages.loadOriginalHttpPostError);
return;
}
if (bidix.debugMode)
alert(original.substr(0,500)+"\n...");
// Locate the storeArea div's
var posDiv = locateStoreArea(original);
if((posDiv[0] == -1) || (posDiv[1] == -1)) {
alert(config.messages.invalidFileError.format([localPath]));
return;
}
bidix.upload.uploadRss(uploadParams,original,posDiv);
};
if(onlyIfDirty && !store.isDirty())
return;
clearMessage();
// save on localdisk ?
if (document.location.toString().substr(0,4) == "file") {
var path = document.location.toString();
var localPath = getLocalPath(path);
saveChanges();
}
// get original
var uploadParams = new Array(storeUrl,toFilename,uploadDir,backupDir,username,password);
var originalPath = document.location.toString();
// If url is a directory : add index.html
if (originalPath.charAt(originalPath.length-1) == "/")
originalPath = originalPath + "index.html";
var dest = config.macros.upload.destFile(storeUrl,toFilename,uploadDir);
var log = new bidix.UploadLog();
log.startUpload(storeUrl, dest, uploadDir, backupDir);
displayMessage(bidix.upload.messages.aboutToSaveOnHttpPost.format([dest]));
if (bidix.debugMode)
alert("about to execute Http - GET on "+originalPath);
var r = doHttp("GET",originalPath,null,null,username,password,callback,uploadParams,null);
if (typeof r == "string")
displayMessage(r);
return r;
};
bidix.upload.uploadRss = function(uploadParams,original,posDiv)
{
var callback = function(status,params,responseText,url,xhr) {
if(status) {
var destfile = responseText.substring(responseText.indexOf("destfile:")+9,responseText.indexOf("\n", responseText.indexOf("destfile:")));
displayMessage(bidix.upload.messages.rssSaved,bidix.dirname(url)+'/'+destfile);
bidix.upload.uploadMain(params[0],params[1],params[2]);
} else {
displayMessage(bidix.upload.messages.rssFailed);
}
};
// do uploadRss
if(config.options.chkGenerateAnRssFeed) {
var rssPath = uploadParams[1].substr(0,uploadParams[1].lastIndexOf(".")) + ".xml";
var rssUploadParams = new Array(uploadParams[0],rssPath,uploadParams[2],'',uploadParams[4],uploadParams[5]);
var rssString = generateRss();
// no UnicodeToUTF8 conversion needed when location is "file" !!!
if (document.location.toString().substr(0,4) != "file")
rssString = convertUnicodeToUTF8(rssString);
bidix.upload.httpUpload(rssUploadParams,rssString,callback,Array(uploadParams,original,posDiv));
} else {
bidix.upload.uploadMain(uploadParams,original,posDiv);
}
};
bidix.upload.uploadMain = function(uploadParams,original,posDiv)
{
var callback = function(status,params,responseText,url,xhr) {
var log = new bidix.UploadLog();
if(status) {
// if backupDir specified
if ((params[3]) && (responseText.indexOf("backupfile:") > -1)) {
var backupfile = responseText.substring(responseText.indexOf("backupfile:")+11,responseText.indexOf("\n", responseText.indexOf("backupfile:")));
displayMessage(bidix.upload.messages.backupSaved,bidix.dirname(url)+'/'+backupfile);
}
var destfile = responseText.substring(responseText.indexOf("destfile:")+9,responseText.indexOf("\n", responseText.indexOf("destfile:")));
displayMessage(bidix.upload.messages.mainSaved,bidix.dirname(url)+'/'+destfile);
store.setDirty(false);
log.endUpload("ok");
} else {
alert(bidix.upload.messages.mainFailed);
displayMessage(bidix.upload.messages.mainFailed);
log.endUpload("failed");
}
};
// do uploadMain
var revised = bidix.upload.updateOriginal(original,posDiv);
bidix.upload.httpUpload(uploadParams,revised,callback,uploadParams);
};
bidix.upload.httpUpload = function(uploadParams,data,callback,params)
{
var localCallback = function(status,params,responseText,url,xhr) {
url = (url.indexOf("nocache=") < 0 ? url : url.substring(0,url.indexOf("nocache=")-1));
if (xhr.status == 404)
alert(bidix.upload.messages.storePhpNotFound.format([url]));
if ((bidix.debugMode) || (responseText.indexOf("Debug mode") >= 0 )) {
alert(responseText);
if (responseText.indexOf("Debug mode") >= 0 )
responseText = responseText.substring(responseText.indexOf("\n\n")+2);
} else if (responseText.charAt(0) != '0')
alert(responseText);
if (responseText.charAt(0) != '0')
status = null;
callback(status,params,responseText,url,xhr);
};
// do httpUpload
var boundary = "---------------------------"+"AaB03x";
var uploadFormName = "UploadPlugin";
// compose headers data
var sheader = "";
sheader += "--" + boundary + "\r\nContent-disposition: form-data; name=\"";
sheader += uploadFormName +"\"\r\n\r\n";
sheader += "backupDir="+uploadParams[3] +
";user=" + uploadParams[4] +
";password=" + uploadParams[5] +
";uploaddir=" + uploadParams[2];
if (bidix.debugMode)
sheader += ";debug=1";
sheader += ";;\r\n";
sheader += "\r\n" + "--" + boundary + "\r\n";
sheader += "Content-disposition: form-data; name=\"userfile\"; filename=\""+uploadParams[1]+"\"\r\n";
sheader += "Content-Type: text/html;charset=UTF-8" + "\r\n";
sheader += "Content-Length: " + data.length + "\r\n\r\n";
// compose trailer data
var strailer = new String();
strailer = "\r\n--" + boundary + "--\r\n";
data = sheader + data + strailer;
if (bidix.debugMode) alert("about to execute Http - POST on "+uploadParams[0]+"\n with \n"+data.substr(0,500)+ " ... ");
var r = doHttp("POST",uploadParams[0],data,"multipart/form-data; ;charset=UTF-8; boundary="+boundary,uploadParams[4],uploadParams[5],localCallback,params,null);
if (typeof r == "string")
displayMessage(r);
return r;
};
// same as Saving's updateOriginal but without convertUnicodeToUTF8 calls
bidix.upload.updateOriginal = function(original, posDiv)
{
if (!posDiv)
posDiv = locateStoreArea(original);
if((posDiv[0] == -1) || (posDiv[1] == -1)) {
alert(config.messages.invalidFileError.format([localPath]));
return;
}
var revised = original.substr(0,posDiv[0] + startSaveArea.length) + "\n" +
store.allTiddlersAsHtml() + "\n" +
original.substr(posDiv[1]);
var newSiteTitle = getPageTitle().htmlEncode();
revised = revised.replaceChunk("<title"+">","</title"+">"," " + newSiteTitle + " ");
revised = updateMarkupBlock(revised,"PRE-HEAD","MarkupPreHead");
revised = updateMarkupBlock(revised,"POST-HEAD","MarkupPostHead");
revised = updateMarkupBlock(revised,"PRE-BODY","MarkupPreBody");
revised = updateMarkupBlock(revised,"POST-SCRIPT","MarkupPostBody");
return revised;
};
//
// UploadLog
//
// config.options.chkUploadLog :
// false : no logging
// true : logging
// config.options.txtUploadLogMaxLine :
// -1 : no limit
// 0 : no Log lines but UploadLog is still in place
// n : the last n lines are only kept
// NaN : no limit (-1)
bidix.UploadLog = function() {
if (!config.options.chkUploadLog)
return; // this.tiddler = null
this.tiddler = store.getTiddler("UploadLog");
if (!this.tiddler) {
this.tiddler = new Tiddler();
this.tiddler.title = "UploadLog";
this.tiddler.text = "| !date | !user | !location | !storeUrl | !uploadDir | !toFilename | !backupdir | !origin |";
this.tiddler.created = new Date();
this.tiddler.modifier = config.options.txtUserName;
this.tiddler.modified = new Date();
store.addTiddler(this.tiddler);
}
return this;
};
bidix.UploadLog.prototype.addText = function(text) {
if (!this.tiddler)
return;
// retrieve maxLine when we need it
var maxLine = parseInt(config.options.txtUploadLogMaxLine,10);
if (isNaN(maxLine))
maxLine = -1;
// add text
if (maxLine != 0)
this.tiddler.text = this.tiddler.text + text;
// Trunck to maxLine
if (maxLine >= 0) {
var textArray = this.tiddler.text.split('\n');
if (textArray.length > maxLine + 1)
textArray.splice(1,textArray.length-1-maxLine);
this.tiddler.text = textArray.join('\n');
}
// update tiddler fields
this.tiddler.modifier = config.options.txtUserName;
this.tiddler.modified = new Date();
store.addTiddler(this.tiddler);
// refresh and notifiy for immediate update
story.refreshTiddler(this.tiddler.title);
store.notify(this.tiddler.title, true);
};
bidix.UploadLog.prototype.startUpload = function(storeUrl, toFilename, uploadDir, backupDir) {
if (!this.tiddler)
return;
var now = new Date();
var text = "\n| ";
var filename = bidix.basename(document.location.toString());
if (!filename) filename = '/';
text += now.formatString("0DD/0MM/YYYY 0hh:0mm:0ss") +" | ";
text += config.options.txtUserName + " | ";
text += "[["+filename+"|"+location + "]] |";
text += " [[" + bidix.basename(storeUrl) + "|" + storeUrl + "]] | ";
text += uploadDir + " | ";
text += "[[" + bidix.basename(toFilename) + " | " +toFilename + "]] | ";
text += backupDir + " |";
this.addText(text);
};
bidix.UploadLog.prototype.endUpload = function(status) {
if (!this.tiddler)
return;
this.addText(" "+status+" |");
};
//
// Utilities
//
bidix.checkPlugin = function(plugin, major, minor, revision) {
var ext = version.extensions[plugin];
if (!
(ext &&
((ext.major > major) ||
((ext.major == major) && (ext.minor > minor)) ||
((ext.major == major) && (ext.minor == minor) && (ext.revision >= revision))))) {
// write error in PluginManager
if (pluginInfo)
pluginInfo.log.push("Requires " + plugin + " " + major + "." + minor + "." + revision);
eval(plugin); // generate an error : "Error: ReferenceError: xxxx is not defined"
}
};
bidix.dirname = function(filePath) {
if (!filePath)
return;
var lastpos;
if ((lastpos = filePath.lastIndexOf("/")) != -1) {
return filePath.substring(0, lastpos);
} else {
return filePath.substring(0, filePath.lastIndexOf("\\"));
}
};
bidix.basename = function(filePath) {
if (!filePath)
return;
var lastpos;
if ((lastpos = filePath.lastIndexOf("#")) != -1)
filePath = filePath.substring(0, lastpos);
if ((lastpos = filePath.lastIndexOf("/")) != -1) {
return filePath.substring(lastpos + 1);
} else
return filePath.substring(filePath.lastIndexOf("\\")+1);
};
bidix.initOption = function(name,value) {
if (!config.options[name])
config.options[name] = value;
};
//
// Initializations
//
// require PasswordOptionPlugin 1.0.1 or better
bidix.checkPlugin("PasswordOptionPlugin", 1, 0, 1);
// styleSheet
setStylesheet('.txtUploadStoreUrl, .txtUploadBackupDir, .txtUploadDir {width: 22em;}',"uploadPluginStyles");
//optionsDesc
merge(config.optionsDesc,{
txtUploadStoreUrl: "Url of the UploadService script (default: store.php)",
txtUploadFilename: "Filename of the uploaded file (default: in index.html)",
txtUploadDir: "Relative Directory where to store the file (default: . (downloadService directory))",
txtUploadBackupDir: "Relative Directory where to backup the file. If empty no backup. (default: ''(empty))",
txtUploadUserName: "Upload Username",
pasUploadPassword: "Upload Password",
chkUploadLog: "do Logging in UploadLog (default: true)",
txtUploadLogMaxLine: "Maximum of lines in UploadLog (default: 10)"
});
// Options Initializations
bidix.initOption('txtUploadStoreUrl','');
bidix.initOption('txtUploadFilename','');
bidix.initOption('txtUploadDir','');
bidix.initOption('txtUploadBackupDir','');
bidix.initOption('txtUploadUserName','');
bidix.initOption('pasUploadPassword','');
bidix.initOption('chkUploadLog',true);
bidix.initOption('txtUploadLogMaxLine','10');
// Backstage
merge(config.tasks,{
uploadOptions: {text: "upload", tooltip: "Change UploadOptions and Upload", content: '<<uploadOptions>>'}
});
config.backstageTasks.push("uploadOptions");
//}}}
<!--{{{-->
<div>
<span class='title' macro='view title'></span>
<span class='toolbar' macro='toolbar [[ToolbarCommands::ViewToolbar]]'></span>
<span macro="showWhen config.options.chkEditMode==true">
<span macro="hideWhenTagged NOTES">
<span class='toolbar' macro='toolbar reload'></span>
</span>
<span macro='showWhenTaggedAny CONTENT FIGURE TABLE BOX NOTES'>
<span class='toolbar' macro='toolbar easyEdit'></span>
</span>
</span>
</div>
<span macro="showWhen config.options.txtUserName==config.options.adminUserName">
<div class='toolbar alignright' macro='toolbar [[ToolbarCommands::AdminOptions]]'></div>
</span>
<span macro="showWhenTaggedAny L2wrapper CONTENT NOTES 'Getting started'">
<div class='tagged' macro='tags'></div>
</span>
<div class='viewer' macro='view text wikified'></div>
<div class='tagClear'></div>
<span macro="foldHeadingsPlus closed"></span>
<span macro="SCImagePrefix"></span>
<!-- <div class='toolbar' macro='collapseOthers'></div> this will collapse all other tiddlers when opening a new tiddler -->
<!--}}}-->
!Field Search
With the Field Search you can restrict your search to certain fields of a tiddler, e.g only search the tags or only the titles. The general form is //fieldname//'':''//textToSearch// (e.g. {{{title:intro}}}). In addition one-character shortcuts are also supported for the standard fields {{{title}}}, {{{text}}} and {{{tags}}}:
|!What you want|!What you type|!Example|
|Search ''titles only''|start word with ''!''|{{{!jonny}}} (shortcut for {{{title:jonny}}})|
|Search ''contents/text only''|start word with ''%''|{{{%football}}} (shortcut for {{{text:football}}})|
|Search ''tags only''|start word with ''#''|{{{#Plugin}}} (shortcut for {{{tags:Plugin}}})|
Using this feature you may also search the extended fields ("Metadata") introduced with TiddlyWiki 2.1, e.g. use {{{priority:1}}} to find all tiddlers with the priority field set to "1".
You may search a word in more than one field. E.g. {{{!#Plugin}}} (or {{{title:tags:Plugin}}} in the "long form") finds tiddlers containing "Plugin" either in the title or in the tags (but does not look for "Plugin" in the text).
!Boolean Search
The Boolean Search is useful when searching for multiple words.
|!What you want|!What you type|!Example|
|''All words'' must exist|List of words|{{{jonny jeremy}}} (or {{{jonny and jeremy}}})|
|''At least one word'' must exist|Separate words by ''or''|{{{jonny or jeremy}}}|
|A word ''must not exist''|Start word with ''-''|{{{-jonny}}} (or {{{not jonny}}})|
''Note:'' When you specify two words, separated with a space, YourSearch finds all tiddlers that contain both words, but not necessarily next to each other. If you want to find a sequence of word, e.g. '{{{John Brown}}}', you need to put the words into quotes. I.e. you type: {{{"john brown"}}}.
Using parenthesis you may change the default "left to right" evaluation of the boolean search. E.g. {{{not (jonny or jeremy)}}} finds all tiddlers that contain neither "jonny" nor "jeremy. In contrast to this {{{not jonny or jeremy}}} (i.e. without parenthesis) finds all tiddlers that either don't contain "jonny" or that contain "jeremy".
!'Exact Word' Search
By default a search result all matches that 'contain' the searched text. E.g. if you search for {{{Task}}} you will get all tiddlers containing 'Task', but also '~CompletedTask', '~TaskForce' etc.
If you only want to get the tiddlers that contain 'exactly the word' you need to prefix it with a '='. E.g. typing '=Task' will find the tiddlers that contain the word 'Task', ignoring words that just contain 'Task' as a substring.
!~CaseSensitiveSearch and ~RegExpSearch
The standard search options ~CaseSensitiveSearch and ~RegExpSearch are fully supported by YourSearch. However when ''~RegExpSearch'' is on Filtered and Boolean Search are disabled.
In addition you may do a "regular expression" search even with the ''~RegExpSearch'' set to false by directly entering the regular expression into the search field, framed with {{{/.../}}}.
Example: {{{/m[ae][iy]er/}}} will find all tiddlers that contain either "maier", "mayer", "meier" or "meyer".
!~JavaScript Expression Filtering
If you are familiar with JavaScript programming and know some TiddlyWiki internals you may also use JavaScript expression for the search. Just enter a JavaScript boolean expression into the search field, framed with {{{ { ... } }}}. In the code refer to the variable tiddler and evaluate to {{{true}}} when the given tiddler should be included in the result.
Example: {{{ { tiddler.modified > new Date("Jul 4, 2005")} }}} returns all tiddler modified after July 4th, 2005.
!Combined Search
You are free to combine the various search options.
''Examples''
|!What you type|!Result|
|{{{!jonny !jeremy -%football}}}|all tiddlers with both {{{jonny}}} and {{{jeremy}}} in its titles, but no {{{football}}} in content.|
|{{{#=Task}}}|All tiddlers tagged with 'Task' (the exact word). Tags named '~CompletedTask', '~TaskForce' etc. are not considered.|
!Access Keys
You are encouraged to use the access keys (also called "shortcut" keys) for the most frequently used operations. For quick reference these shortcuts are also mentioned in the tooltip for the various buttons etc.
|!Key|!Operation|
|{{{Alt-F}}}|''The most important keystroke'': It moves the cursor to the search input field so you can directly start typing your query. Pressing {{{Alt-F}}} will also display the previous search result. This way you can quickly display multiple tiddlers using "Press {{{Alt-F}}}. Select tiddler." sequences.|
|{{{ESC}}}|Closes the [[YourSearch Result]]. When the [[YourSearch Result]] is already closed and the cursor is in the search input field the field's content is cleared so you start a new query.|
|{{{Alt-1}}}, {{{Alt-2}}},... |Pressing these keys opens the first, second etc. tiddler from the result list.|
|{{{Alt-O}}}|Opens all found tiddlers.|
|{{{Alt-P}}}|Toggles the 'Preview Text' mode.|
|{{{Alt-'<'}}}, {{{Alt-'>'}}}|Displays the previous or next page in the [[YourSearch Result]].|
|{{{Return}}}|When you have turned off the 'as you type' search mode pressing the {{{Return}}} key actually starts the search (as does pressing the 'search' button).|
//If some of these shortcuts don't work for you check your browser if you have other extensions installed that already "use" these shortcuts.//
<!--{{{-->
<span class='yourSearchNumber' macro='foundTiddler number'></span>
<span class='yourSearchTitle' macro='foundTiddler title'/></span> -
<span macro='foundTiddler field includeURL'/></span> -
<span class='yourSearchTags' macro='foundTiddler field tags 50'/></span>
<span macro="yourSearch if previewText"><div class='yourSearchText' macro='foundTiddler field text 250'/></div></span>
<!--}}}-->
/***
|''Name:''|YourSearchPlugin|
|''Version:''|2.1.5 (2010-02-16)|
|''Source:''|http://tiddlywiki.abego-software.de/#YourSearchPlugin|
|''Author:''|UdoBorkowski (ub [at] abego-software [dot] de)|
|''Licence:''|[[BSD open source license (abego Software)|http://www.abego-software.de/legal/apl-v10.html]]|
|''Copyright:''|© 2005-2010 [[abego Software|http://www.abego-software.de]]|
|''~CoreVersion:''|2.1.0|
|''Community:''|[[del.icio.us|http://del.icio.us/post?url=http://tiddlywiki.abego-software.de/index.html%23YourSearchPlugin]]|
|''Browser:''|Firefox 1.0.4+; Firefox 1.5; ~InternetExplorer 6.0|
!About YourSearch
YourSearch gives you a bunch of new features to simplify and speed up your daily searches in TiddlyWiki. It seamlessly integrates into the standard TiddlyWiki search: just start typing into the 'search' field and explore!
For more information see [[Help|YourSearch Help]].
!Compatibility
This plugin requires TiddlyWiki 2.1.
Check the [[archive|http://tiddlywiki.abego-software.de/archive]] for ~YourSearchPlugins supporting older versions of TiddlyWiki.
!Source Code
***/
/***
This plugin's source code is compressed (and hidden). Use this [[link|http://tiddlywiki.abego-software.de/archive/YourSearchPlugin/Plugin-YourSearch-src.2.1.5.js]] to get the readable source code.
***/
///%
if(!version.extensions.YourSearchPlugin){version.extensions.YourSearchPlugin={major:2,minor:1,revision:5,source:"http://tiddlywiki.abego-software.de/#YourSearchPlugin",licence:"[[BSD open source license (abego Software)|http://www.abego-software.de/legal/apl-v10.html]]",copyright:"Copyright (c) abego Software GmbH, 2005-2010 (www.abego-software.de)"};if(!window.abego){window.abego={};}if(!Array.forEach){Array.forEach=function(_1,_2,_3){for(var i=0,_4=_1.length;i<_4;i++){_2.call(_3,_1[i],i,_1);}};Array.prototype.forEach=function(_5,_6){for(var i=0,_7=this.length;i<_7;i++){_5.call(_6,this[i],i,this);}};}abego.toInt=function(s,_8){if(!s){return _8;}var n=parseInt(s);return (n==NaN)?_8:n;};abego.createEllipsis=function(_9){var e=createTiddlyElement(_9,"span");e.innerHTML="…";};abego.shallowCopy=function(_a){if(!_a){return _a;}var _b={};for(var n in _a){_b[n]=_a[n];}return _b;};abego.copyOptions=function(_c){return !_c?{}:abego.shallowCopy(_c);};abego.countStrings=function(_d,s){if(!s){return 0;}var _e=s.length;var n=0;var _f=0;while(1){var i=_d.indexOf(s,_f);if(i<0){return n;}n++;_f=i+_e;}return n;};abego.getBracedText=function(_10,_11,_12){if(!_11){_11=0;}var re=/\{([^\}]*)\}/gm;re.lastIndex=_11;var m=re.exec(_10);if(m){var s=m[1];var _13=abego.countStrings(s,"{");if(!_13){if(_12){_12.lastIndex=re.lastIndex;}return s;}var len=_10.length;for(var i=re.lastIndex;i<len&&_13;i++){var c=_10.charAt(i);if(c=="{"){_13++;}else{if(c=="}"){_13--;}}}if(!_13){if(_12){_12.lastIndex=i-1;}return _10.substring(m.index+1,i-1);}}};abego.select=function(_14,_15,_16,_17){if(!_17){_17=[];}_14.forEach(function(t){if(_15.call(_16,t)){_17.push(t);}});return _17;};abego.consumeEvent=function(e){if(e.stopPropagation){e.stopPropagation();}if(e.preventDefault){e.preventDefault();}e.cancelBubble=true;e.returnValue=true;};abego.TiddlerFilterTerm=function(_18,_19){if(!_19){_19={};}var _1a=_18;if(!_19.textIsRegExp){_1a=_18.escapeRegExp();if(_19.fullWordMatch){_1a="\\b"+_1a+"\\b";}}var _1b=new RegExp(_1a,"m"+(_19.caseSensitive?"":"i"));this.tester=new abego.MultiFieldRegExpTester(_1b,_19.fields,_19.withExtendedFields);};abego.TiddlerFilterTerm.prototype.test=function(_1c){return this.tester.test(_1c);};abego.parseNewTiddlerCommandLine=function(s){var m=/(.*?)\.(?:\s+|$)([^#]*)(#.*)?/.exec(s);if(!m){m=/([^#]*)()(#.*)?/.exec(s);}if(m){var r;if(m[3]){var s2=m[3].replace(/#/g,"");r=s2.parseParams("tag");}else{r=[[]];}var _1d=m[2]?m[2].trim():"";r.push({name:"text",value:_1d});r[0].text=[_1d];return {title:m[1].trim(),params:r};}else{return {title:s.trim(),params:[[]]};}};abego.parseTiddlerFilterTerm=function(_1e,_1f,_20){var re=/\s*(?:(?:\{([^\}]*)\})|(?:(=)|([#%!])|(?:(\w+)\s*\:(?!\/\/))|(?:(?:("(?:(?:\\")|[^"])+")|(?:\/((?:(?:\\\/)|[^\/])+)\/)|(\w+\:\/\/[^\s]+)|([^\s\)\-\"]+)))))/mg;var _21={"!":"title","%":"text","#":"tags"};var _22={};var _23;re.lastIndex=_1f;while(1){var i=re.lastIndex;var m=re.exec(_1e);if(!m||m.index!=i){throw "Word or String literal expected";}if(m[1]){var _24={};var _25=abego.getBracedText(_1e,0,_24);if(!_25){throw "Invalid {...} syntax";}var f=Function("tiddler","return ("+_25+");");return {func:f,lastIndex:_24.lastIndex,markRE:null};}if(m[2]){_23=true;}else{if(m[3]){_22[_21[m[3]]]=1;}else{if(m[4]){_22[m[4]]=1;}else{var _26=m[6];var _27=m[5]?window.eval(m[5]):m[6]?m[6]:m[7]?m[7]:m[8];var _20=abego.copyOptions(_20);_20.fullWordMatch=_23;_20.textIsRegExp=_26;var _28=[];for(var n in _22){_28.push(n);}if(_28.length==0){_20.fields=_20.defaultFields;}else{_20.fields=_28;_20.withExtendedFields=false;}var _29=new abego.TiddlerFilterTerm(_27,_20);var _2a=_26?_27:_27.escapeRegExp();if(_2a&&_23){_2a="\\b"+_2a+"\\b";}return {func:function(_2b){return _29.test(_2b);},lastIndex:re.lastIndex,markRE:_2a?"(?:"+_2a+")":null};}}}}};abego.BoolExp=function(s,_2c,_2d){this.s=s;var _2e=_2d&&_2d.defaultOperationIs_OR;var _2f=/\s*(?:(\-|not)|(\())/gi;var _30=/\s*\)/g;var _31=/\s*(?:(and|\&\&)|(or|\|\|))/gi;var _32=/\s*[^\)\s]/g;var _33=/\s*(\-|not)?(\s*\()?/gi;var _34;var _35=function(_36){_33.lastIndex=_36;var m=_33.exec(s);var _37;var _38;if(m&&m.index==_36){_36+=m[0].length;_37=m[1];if(m[2]){var e=_34(_36);_30.lastIndex=e.lastIndex;if(!_30.exec(s)){throw "Missing ')'";}_38={func:e.func,lastIndex:_30.lastIndex,markRE:e.markRE};}}if(!_38){_38=_2c(s,_36,_2d);}if(_37){_38.func=(function(f){return function(_39){return !f(_39);};})(_38.func);_38.markRE=null;}return _38;};_34=function(_3a){var _3b=_35(_3a);while(1){var l=_3b.lastIndex;_31.lastIndex=l;var m=_31.exec(s);var _3c;var _3d;if(m&&m.index==l){_3c=!m[1];_3d=_35(_31.lastIndex);}else{try{_3d=_35(l);}catch(e){return _3b;}_3c=_2e;}_3b.func=(function(_3e,_3f,_40){return _40?function(_41){return _3e(_41)||_3f(_41);}:function(_42){return _3e(_42)&&_3f(_42);};})(_3b.func,_3d.func,_3c);_3b.lastIndex=_3d.lastIndex;if(!_3b.markRE){_3b.markRE=_3d.markRE;}else{if(_3d.markRE){_3b.markRE=_3b.markRE+"|"+_3d.markRE;}}}};var _43=_34(0);this.evalFunc=_43.func;if(_43.markRE){this.markRegExp=new RegExp(_43.markRE,_2d.caseSensitive?"mg":"img");}};abego.BoolExp.prototype.exec=function(){return this.evalFunc.apply(this,arguments);};abego.BoolExp.prototype.getMarkRegExp=function(){return this.markRegExp;};abego.BoolExp.prototype.toString=function(){return this.s;};abego.MultiFieldRegExpTester=function(re,_44,_45){this.re=re;this.fields=_44?_44:["title","text","tags"];this.withExtendedFields=_45;};abego.MultiFieldRegExpTester.prototype.test=function(_46){var re=this.re;for(var i=0;i<this.fields.length;i++){var s=store.getValue(_46,this.fields[i]);if(typeof s=="string"&&re.test(s)){return this.fields[i];}}if(this.withExtendedFields){return store.forEachField(_46,function(_47,_48,_49){return typeof _49=="string"&&re.test(_49)?_48:null;},true);}return null;};abego.TiddlerQuery=function(_4a,_4b,_4c,_4d,_4e){if(_4c){this.regExp=new RegExp(_4a,_4b?"mg":"img");this.tester=new abego.MultiFieldRegExpTester(this.regExp,_4d,_4e);}else{this.expr=new abego.BoolExp(_4a,abego.parseTiddlerFilterTerm,{defaultFields:_4d,caseSensitive:_4b,withExtendedFields:_4e});}this.getQueryText=function(){return _4a;};this.getUseRegExp=function(){return _4c;};this.getCaseSensitive=function(){return _4b;};this.getDefaultFields=function(){return _4d;};this.getWithExtendedFields=function(){return _4e;};};abego.TiddlerQuery.prototype.test=function(_4f){if(!_4f){return false;}if(this.regExp){return this.tester.test(_4f);}return this.expr.exec(_4f);};abego.TiddlerQuery.prototype.filter=function(_50){return abego.select(_50,this.test,this);};abego.TiddlerQuery.prototype.getMarkRegExp=function(){if(this.regExp){return "".search(this.regExp)>=0?null:this.regExp;}return this.expr.getMarkRegExp();};abego.TiddlerQuery.prototype.toString=function(){return (this.regExp?this.regExp:this.expr).toString();};abego.PageWiseRenderer=function(){this.firstIndexOnPage=0;};merge(abego.PageWiseRenderer.prototype,{setItems:function(_51){this.items=_51;this.setFirstIndexOnPage(0);},getMaxPagesInNavigation:function(){return 10;},getItemsCount:function(_52){return this.items?this.items.length:0;},getCurrentPageIndex:function(){return Math.floor(this.firstIndexOnPage/this.getItemsPerPage());},getLastPageIndex:function(){return Math.floor((this.getItemsCount()-1)/this.getItemsPerPage());},setFirstIndexOnPage:function(_53){this.firstIndexOnPage=Math.min(Math.max(0,_53),this.getItemsCount()-1);},getFirstIndexOnPage:function(){this.firstIndexOnPage=Math.floor(this.firstIndexOnPage/this.getItemsPerPage())*this.getItemsPerPage();return this.firstIndexOnPage;},getLastIndexOnPage:function(){return Math.min(this.getFirstIndexOnPage()+this.getItemsPerPage()-1,this.getItemsCount()-1);},onPageChanged:function(_54,_55){},renderPage:function(_56){if(_56.beginRendering){_56.beginRendering(this);}try{if(this.getItemsCount()){var _57=this.getLastIndexOnPage();var _58=-1;for(var i=this.getFirstIndexOnPage();i<=_57;i++){_58++;_56.render(this,this.items[i],i,_58);}}}finally{if(_56.endRendering){_56.endRendering(this);}}},addPageNavigation:function(_59){if(!this.getItemsCount()){return;}var _5a=this;var _5b=function(e){if(!e){var e=window.event;}abego.consumeEvent(e);var _5c=abego.toInt(this.getAttribute("page"),0);var _5d=_5a.getCurrentPageIndex();if(_5c==_5d){return;}var _5e=_5c*_5a.getItemsPerPage();_5a.setFirstIndexOnPage(_5e);_5a.onPageChanged(_5c,_5d);};var _5f;var _60=this.getCurrentPageIndex();var _61=this.getLastPageIndex();if(_60>0){_5f=createTiddlyButton(_59,"Previous","Go to previous page (Shortcut: Alt-'<')",_5b,"prev");_5f.setAttribute("page",(_60-1).toString());_5f.setAttribute("accessKey","<");}for(var i=-this.getMaxPagesInNavigation();i<this.getMaxPagesInNavigation();i++){var _62=_60+i;if(_62<0){continue;}if(_62>_61){break;}var _63=(i+_60+1).toString();var _64=_62==_60?"currentPage":"otherPage";_5f=createTiddlyButton(_59,_63,"Go to page %0".format([_63]),_5b,_64);_5f.setAttribute("page",(_62).toString());}if(_60<_61){_5f=createTiddlyButton(_59,"Next","Go to next page (Shortcut: Alt-'>')",_5b,"next");_5f.setAttribute("page",(_60+1).toString());_5f.setAttribute("accessKey",">");}}});abego.LimitedTextRenderer=function(){var _65=40;var _66=4;var _67=function(_68,_69,_6a){var n=_68.length;if(n==0){_68.push({start:_69,end:_6a});return;}var i=0;for(;i<n;i++){var _6b=_68[i];if(_6b.start<=_6a&&_69<=_6b.end){var r;var _6c=i+1;for(;_6c<n;_6c++){r=_68[_6c];if(r.start>_6a||_69>_6b.end){break;}}var _6d=_69;var _6e=_6a;for(var j=i;j<_6c;j++){r=_68[j];_6d=Math.min(_6d,r.start);_6e=Math.max(_6e,r.end);}_68.splice(i,_6c-i,{start:_6d,end:_6e});return;}if(_6b.start>_6a){break;}}_68.splice(i,0,{start:_69,end:_6a});};var _6f=function(_70){var _71=0;for(var i=0;i<_70.length;i++){var _72=_70[i];_71+=_72.end-_72.start;}return _71;};var _73=function(c){return (c>="a"&&c<="z")||(c>="A"&&c<="Z")||c=="_";};var _74=function(s,_75){if(!_73(s[_75])){return null;}for(var i=_75-1;i>=0&&_73(s[i]);i--){}var _76=i+1;var n=s.length;for(i=_75+1;i<n&&_73(s[i]);i++){}return {start:_76,end:i};};var _77=function(s,_78,_79){var _7a;if(_79){_7a=_74(s,_78);}else{if(_78<=0){return _78;}_7a=_74(s,_78-1);}if(!_7a){return _78;}if(_79){if(_7a.start>=_78-_66){return _7a.start;}if(_7a.end<=_78+_66){return _7a.end;}}else{if(_7a.end<=_78+_66){return _7a.end;}if(_7a.start>=_78-_66){return _7a.start;}}return _78;};var _7b=function(s,_7c){var _7d=[];if(_7c){var _7e=0;var n=s.length;var _7f=0;do{_7c.lastIndex=_7e;var _80=_7c.exec(s);if(_80){if(_7e<_80.index){var t=s.substring(_7e,_80.index);_7d.push({text:t});}_7d.push({text:_80[0],isMatch:true});_7e=_80.index+_80[0].length;}else{_7d.push({text:s.substr(_7e)});break;}}while(true);}else{_7d.push({text:s});}return _7d;};var _81=function(_82){var _83=0;for(var i=0;i<_82.length;i++){if(_82[i].isMatch){_83++;}}return _83;};var _84=function(s,_85,_86,_87,_88){var _89=Math.max(Math.floor(_88/(_87+1)),_65);var _8a=Math.max(_89-(_86-_85),0);var _8b=Math.min(Math.floor(_86+_8a/3),s.length);var _8c=Math.max(_8b-_89,0);_8c=_77(s,_8c,true);_8b=_77(s,_8b,false);return {start:_8c,end:_8b};};var _8d=function(_8e,s,_8f){var _90=[];var _91=_81(_8e);var pos=0;for(var i=0;i<_8e.length;i++){var t=_8e[i];var _92=t.text;if(t.isMatch){var _93=_84(s,pos,pos+_92.length,_91,_8f);_67(_90,_93.start,_93.end);}pos+=_92.length;}return _90;};var _94=function(s,_95,_96){var _97=_96-_6f(_95);while(_97>0){if(_95.length==0){_67(_95,0,_77(s,_96,false));return;}else{var _98=_95[0];var _99;var _9a;if(_98.start==0){_99=_98.end;if(_95.length>1){_9a=_95[1].start;}else{_67(_95,_99,_77(s,_99+_97,false));return;}}else{_99=0;_9a=_98.start;}var _9b=Math.min(_9a,_99+_97);_67(_95,_99,_9b);_97-=(_9b-_99);}}};var _9c=function(_9d,s,_9e,_9f,_a0){if(_9f.length==0){return;}var _a1=function(_a2,s,_a3,_a4,_a5){var t;var _a6;var pos=0;var i=0;var _a7=0;for(;i<_a3.length;i++){t=_a3[i];_a6=t.text;if(_a4<pos+_a6.length){_a7=_a4-pos;break;}pos+=_a6.length;}var _a8=_a5-_a4;for(;i<_a3.length&&_a8>0;i++){t=_a3[i];_a6=t.text.substr(_a7);_a7=0;if(_a6.length>_a8){_a6=_a6.substr(0,_a8);}if(t.isMatch){createTiddlyElement(_a2,"span",null,"marked",_a6);}else{createTiddlyText(_a2,_a6);}_a8-=_a6.length;}if(_a5<s.length){abego.createEllipsis(_a2);}};if(_9f[0].start>0){abego.createEllipsis(_9d);}var _a9=_a0;for(var i=0;i<_9f.length&&_a9>0;i++){var _aa=_9f[i];var len=Math.min(_aa.end-_aa.start,_a9);_a1(_9d,s,_9e,_aa.start,_aa.start+len);_a9-=len;}};this.render=function(_ab,s,_ac,_ad){if(s.length<_ac){_ac=s.length;}var _ae=_7b(s,_ad);var _af=_8d(_ae,s,_ac);_94(s,_af,_ac);_9c(_ab,s,_ae,_af,_ac);};};(function(){function _b0(msg){alert(msg);throw msg;};if(version.major<2||(version.major==2&&version.minor<1)){_b0("YourSearchPlugin requires TiddlyWiki 2.1 or newer.\n\nCheck the archive for YourSearch plugins\nsupporting older versions of TiddlyWiki.\n\nArchive: http://tiddlywiki.abego-software.de/archive");}abego.YourSearch={};var _b1;var _b2;var _b3=function(_b4){_b1=_b4;};var _b5=function(){return _b1?_b1:[];};var _b6=function(){return _b1?_b1.length:0;};var _b7=4;var _b8=10;var _b9=2;var _ba=function(s,re){var m=s.match(re);return m?m.length:0;};var _bb=function(_bc,_bd){var _be=_bd.getMarkRegExp();if(!_be){return 1;}var _bf=_bc.title.match(_be);var _c0=_bf?_bf.length:0;var _c1=_ba(_bc.getTags(),_be);var _c2=_bf?_bf.join("").length:0;var _c3=_bc.title.length>0?_c2/_bc.title.length:0;var _c4=_c0*_b7+_c1*_b9+_c3*_b8+1;return _c4;};var _c5=function(_c6,_c7,_c8,_c9,_ca,_cb){_b2=null;var _cc=_c6.reverseLookup("tags",_cb,false);try{var _cd=[];if(config.options.chkSearchInTitle){_cd.push("title");}if(config.options.chkSearchInText){_cd.push("text");}if(config.options.chkSearchInTags){_cd.push("tags");}_b2=new abego.TiddlerQuery(_c7,_c8,_c9,_cd,config.options.chkSearchExtendedFields);}catch(e){return [];}var _ce=_b2.filter(_cc);var _cf=abego.YourSearch.getRankFunction();for(var i=0;i<_ce.length;i++){var _d0=_ce[i];var _d1=_cf(_d0,_b2);_d0.searchRank=_d1;}if(!_ca){_ca="title";}var _d2=function(a,b){var _d3=a.searchRank-b.searchRank;if(_d3==0){if(a[_ca]==b[_ca]){return (0);}else{return (a[_ca]<b[_ca])?-1:+1;}}else{return (_d3>0)?-1:+1;}};_ce.sort(_d2);return _ce;};var _d4=80;var _d5=50;var _d6=250;var _d7=50;var _d8=25;var _d9=10;var _da="yourSearchResult";var _db="yourSearchResultItems";var _dc;var _dd;var _de;var _df;var _e0;var _e1=function(){if(version.extensions.YourSearchPlugin.styleSheetInited){return;}version.extensions.YourSearchPlugin.styleSheetInited=true;setStylesheet(store.getTiddlerText("YourSearchStyleSheet"),"yourSearch");};var _e2=function(){return _dd!=null&&_dd.parentNode==document.body;};var _e3=function(){if(_e2()){document.body.removeChild(_dd);}};var _e4=function(e){_e3();var _e5=this.getAttribute("tiddlyLink");if(_e5){var _e6=this.getAttribute("withHilite");var _e7=highlightHack;if(_e6&&_e6=="true"&&_b2){highlightHack=_b2.getMarkRegExp();}story.displayTiddler(this,_e5);highlightHack=_e7;}return (false);};var _e8=function(){if(!_de){return;}var _e9=_de;var _ea=findPosX(_e9);var _eb=findPosY(_e9);var _ec=_e9.offsetHeight;var _ed=_ea;var _ee=_eb+_ec;var _ef=findWindowWidth();if(_ef<_dd.offsetWidth){_dd.style.width=(_ef-100)+"px";_ef=findWindowWidth();}var _f0=_dd.offsetWidth;if(_ed+_f0>_ef){_ed=_ef-_f0-30;}if(_ed<0){_ed=0;}_dd.style.left=_ed+"px";_dd.style.top=_ee+"px";_dd.style.display="block";};var _f1=function(){if(_dd){window.scrollTo(0,ensureVisible(_dd));}if(_de){window.scrollTo(0,ensureVisible(_de));}};var _f2=function(){_e8();_f1();};var _f3;var _f4;var _f5=new abego.PageWiseRenderer();var _f6=function(_f7){this.itemHtml=store.getTiddlerText("YourSearchItemTemplate");if(!this.itemHtml){_b0("YourSearchItemTemplate not found");}this.place=document.getElementById(_db);if(!this.place){this.place=createTiddlyElement(_f7,"div",_db);}};merge(_f6.prototype,{render:function(_f8,_f9,_fa,_fb){_f3=_fb;_f4=_f9;var _fc=createTiddlyElement(this.place,"div",null,"yourSearchItem");_fc.innerHTML=this.itemHtml;applyHtmlMacros(_fc,null);refreshElements(_fc,null);},endRendering:function(_fd){_f4=null;}});var _fe=function(){if(!_dd||!_de){return;}var _ff=store.getTiddlerText("YourSearchResultTemplate");if(!_ff){_ff="<b>Tiddler YourSearchResultTemplate not found</b>";}_dd.innerHTML=_ff;applyHtmlMacros(_dd,null);refreshElements(_dd,null);var _100=new _f6(_dd);_f5.renderPage(_100);_f2();};_f5.getItemsPerPage=function(){var n=(config.options.chkPreviewText)?abego.toInt(config.options.txtItemsPerPageWithPreview,_d9):abego.toInt(config.options.txtItemsPerPage,_d8);return (n>0)?n:1;};_f5.onPageChanged=function(){_fe();};var _101=function(){if(_de==null||!config.options.chkUseYourSearch){return;}if((_de.value==_dc)&&_dc&&!_e2()){if(_dd&&(_dd.parentNode!=document.body)){document.body.appendChild(_dd);_f2();}else{abego.YourSearch.onShowResult(true);}}};var _102=function(){_e3();_dd=null;_dc=null;};var _103=function(self,e){while(e!=null){if(self==e){return true;}e=e.parentNode;}return false;};var _104=function(e){if(e.target==_de){return;}if(e.target==_df){return;}if(_dd&&_103(_dd,e.target)){return;}_e3();};var _105=function(e){if(e.keyCode==27){_e3();}};addEvent(document,"click",_104);addEvent(document,"keyup",_105);var _106=function(text,_107,_108){_dc=text;_b3(_c5(store,text,_107,_108,"title","excludeSearch"));abego.YourSearch.onShowResult();};var _109=function(_10a,_10b,_10c,_10d,_10e,_10f){_e1();_dc="";var _110=null;var _111=function(txt){if(config.options.chkUseYourSearch){_106(txt.value,config.options.chkCaseSensitiveSearch,config.options.chkRegExpSearch);}else{story.search(txt.value,config.options.chkCaseSensitiveSearch,config.options.chkRegExpSearch);}_dc=txt.value;};var _112=function(e){_111(_de);return false;};var _113=function(e){if(!e){var e=window.event;}_de=this;switch(e.keyCode){case 13:if(e.ctrlKey&&_e0&&_e2()){_e0.onclick.apply(_e0,[e]);}else{_111(this);}break;case 27:if(_e2()){_e3();}else{this.value="";clearMessage();}break;}if(String.fromCharCode(e.keyCode)==this.accessKey||e.altKey){_101();}if(this.value.length<3&&_110){clearTimeout(_110);}if(this.value.length>2){if(this.value!=_dc){if(!config.options.chkUseYourSearch||config.options.chkSearchAsYouType){if(_110){clearTimeout(_110);}var txt=this;_110=setTimeout(function(){_111(txt);},500);}}else{if(_110){clearTimeout(_110);}}}if(this.value.length==0){_e3();}};var _114=function(e){this.select();clearMessage();_101();};var args=_10e.parseParams("list",null,true);var _115=getFlag(args,"buttonAtRight");var _116=getParam(args,"sizeTextbox",this.sizeTextbox);var btn;if(!_115){btn=createTiddlyButton(_10a,this.label,this.prompt,_112);}var txt=createTiddlyElement(null,"input",null,"txtOptionInput searchField",null);if(_10c[0]){txt.value=_10c[0];}txt.onkeyup=_113;txt.onfocus=_114;txt.setAttribute("size",_116);txt.setAttribute("accessKey",this.accessKey);txt.setAttribute("autocomplete","off");if(config.browser.isSafari){txt.setAttribute("type","search");txt.setAttribute("results","5");}else{txt.setAttribute("type","text");}if(_10a){_10a.appendChild(txt);}if(_115){btn=createTiddlyButton(_10a,this.label,this.prompt,_112);}_de=txt;_df=btn;};var _117=function(){_e3();var _118=_b5();var n=_118.length;if(n){var _119=[];for(var i=0;i<n;i++){_119.push(_118[i].title);}story.displayTiddlers(null,_119);}};var _11a=function(_11b,_11c,_11d,_11e){invokeMacro(_11b,"option",_11c,_11d,_11e);var elem=_11b.lastChild;var _11f=elem.onclick;elem.onclick=function(e){var _120=_11f.apply(this,arguments);_fe();return _120;};return elem;};var _121=function(s){var _122=["''","{{{","}}}","//","<<<","/***","***/"];var _123="";for(var i=0;i<_122.length;i++){if(i!=0){_123+="|";}_123+="("+_122[i].escapeRegExp()+")";}return s.replace(new RegExp(_123,"mg"),"").trim();};var _124=function(){var i=_f3;return (i>=0&&i<=9)?(i<9?(i+1):0):-1;};var _125=new abego.LimitedTextRenderer();var _126=function(_127,s,_128){_125.render(_127,s,_128,_b2.getMarkRegExp());};var _129=TiddlyWiki.prototype.saveTiddler;TiddlyWiki.prototype.saveTiddler=function(_12a,_12b,_12c,_12d,_12e,tags,_12f){_129.apply(this,arguments);_102();};var _130=TiddlyWiki.prototype.removeTiddler;TiddlyWiki.prototype.removeTiddler=function(_131){_130.apply(this,arguments);_102();};config.macros.yourSearch={label:"yourSearch",prompt:"Gives access to the current/last YourSearch result",handler:function(_132,_133,_134,_135,_136,_137){if(_134.length==0){return;}var name=_134[0];var func=config.macros.yourSearch.funcs[name];if(func){func(_132,_133,_134,_135,_136,_137);}},tests:{"true":function(){return true;},"false":function(){return false;},"found":function(){return _b6()>0;},"previewText":function(){return config.options.chkPreviewText;}},funcs:{itemRange:function(_138){if(_b6()){var _139=_f5.getLastIndexOnPage();var s="%0 - %1".format([_f5.getFirstIndexOnPage()+1,_139+1]);createTiddlyText(_138,s);}},count:function(_13a){createTiddlyText(_13a,_b6().toString());},query:function(_13b){if(_b2){createTiddlyText(_13b,_b2.toString());}},version:function(_13c){var t="YourSearch %0.%1.%2".format([version.extensions.YourSearchPlugin.major,version.extensions.YourSearchPlugin.minor,version.extensions.YourSearchPlugin.revision]);var e=createTiddlyElement(_13c,"a");e.setAttribute("href","http://tiddlywiki.abego-software.de/#YourSearchPlugin");e.innerHTML="<font color=\"black\" face=\"Arial, Helvetica, sans-serif\">"+t+"<font>";},copyright:function(_13d){var e=createTiddlyElement(_13d,"a");e.setAttribute("href","http://www.abego-software.de");e.innerHTML="<font color=\"black\" face=\"Arial, Helvetica, sans-serif\">© 2005-2008 <b><font color=\"red\">abego</font></b> Software<font>";},newTiddlerButton:function(_13e){if(_b2){var r=abego.parseNewTiddlerCommandLine(_b2.getQueryText());var btn=config.macros.newTiddler.createNewTiddlerButton(_13e,r.title,r.params,"new tiddler","Create a new tiddler based on search text. (Shortcut: Ctrl-Enter; Separators: '.', '#')",null,"text");var _13f=btn.onclick;btn.onclick=function(){_e3();_13f.apply(this,arguments);};_e0=btn;}},linkButton:function(_140,_141,_142,_143,_144,_145){if(_142<2){return;}var _146=_142[1];var text=_142<3?_146:_142[2];var _147=_142<4?text:_142[3];var _148=_142<5?null:_142[4];var btn=createTiddlyButton(_140,text,_147,_e4,null,null,_148);btn.setAttribute("tiddlyLink",_146);},closeButton:function(_149,_14a,_14b,_14c,_14d,_14e){var _14f=createTiddlyButton(_149,"close","Close the Search Results (Shortcut: ESC)",_e3);},openAllButton:function(_150,_151,_152,_153,_154,_155){var n=_b6();if(n==0){return;}var _156=n==1?"open tiddler":"open all %0 tiddlers".format([n]);var _157=createTiddlyButton(_150,_156,"Open all found tiddlers (Shortcut: Alt-O)",_117);_157.setAttribute("accessKey","O");},naviBar:function(_158,_159,_15a,_15b,_15c,_15d){_f5.addPageNavigation(_158);},"if":function(_15e,_15f,_160,_161,_162,_163){if(_160.length<2){return;}var _164=_160[1];var _165=(_164=="not");if(_165){if(_160.length<3){return;}_164=_160[2];}var test=config.macros.yourSearch.tests[_164];var _166=false;try{if(test){_166=test(_15e,_15f,_160,_161,_162,_163)!=_165;}else{_166=(!eval(_164))==_165;}}catch(ex){}if(!_166){_15e.style.display="none";}},chkPreviewText:function(_167,_168,_169,_16a,_16b,_16c){var _16d=_169.slice(1).join(" ");var elem=_11a(_167,"chkPreviewText",_16a,_16c);elem.setAttribute("accessKey","P");elem.title="Show text preview of found tiddlers (Shortcut: Alt-P)";return elem;}}};config.macros.foundTiddler={label:"foundTiddler",prompt:"Provides information on the tiddler currently processed on the YourSearch result page",handler:function(_16e,_16f,_170,_171,_172,_173){var name=_170[0];var func=config.macros.foundTiddler.funcs[name];if(func){func(_16e,_16f,_170,_171,_172,_173);}},funcs:{title:function(_174,_175,_176,_177,_178,_179){if(!_f4){return;}var _17a=_124();var _17b=_17a>=0?"Open tiddler (Shortcut: Alt-%0)".format([_17a.toString()]):"Open tiddler";var btn=createTiddlyButton(_174,null,_17b,_e4,null);btn.setAttribute("tiddlyLink",_f4.title);btn.setAttribute("withHilite","true");_126(btn,_f4.title,_d4);if(_17a>=0){btn.setAttribute("accessKey",_17a.toString());}},tags:function(_17c,_17d,_17e,_17f,_180,_181){if(!_f4){return;}_126(_17c,_f4.getTags(),_d5);},text:function(_182,_183,_184,_185,_186,_187){if(!_f4){return;}_126(_182,_121(_f4.text),_d6);},field:function(_188,_189,_18a,_18b,_18c,_18d){if(!_f4){return;}var name=_18a[1];var len=_18a.length>2?abego.toInt(_18a[2],_d7):_d7;var v=store.getValue(_f4,name);if(v){_126(_188,_121(v),len);}},number:function(_18e,_18f,_190,_191,_192,_193){var _194=_124();if(_194>=0){var text="%0)".format([_194.toString()]);createTiddlyElement(_18e,"span",null,"shortcutNumber",text);}}}};var opts={chkUseYourSearch:true,chkPreviewText:true,chkSearchAsYouType:true,chkSearchInTitle:true,chkSearchInText:true,chkSearchInTags:true,chkSearchExtendedFields:true,txtItemsPerPage:_d8,txtItemsPerPageWithPreview:_d9};for(var n in opts){if(config.options[n]==undefined){config.options[n]=opts[n];}}config.shadowTiddlers.AdvancedOptions+="\n<<option chkUseYourSearch>> Use 'Your Search' //([[more options|YourSearch Options]]) ([[help|YourSearch Help]])// ";config.shadowTiddlers["YourSearch Help"]="!Field Search\nWith the Field Search you can restrict your search to certain fields of a tiddler, e.g"+" only search the tags or only the titles. The general form is //fieldname//'':''//textToSearch// (e."+"g. {{{title:intro}}}). In addition one-character shortcuts are also supported for the standard field"+"s {{{title}}}, {{{text}}} and {{{tags}}}:\n|!What you want|!What you type|!Example|\n|Search ''titles "+"only''|start word with ''!''|{{{!jonny}}} (shortcut for {{{title:jonny}}})|\n|Search ''contents/text "+"only''|start word with ''%''|{{{%football}}} (shortcut for {{{text:football}}})|\n|Search ''tags only"+"''|start word with ''#''|{{{#Plugin}}} (shortcut for {{{tags:Plugin}}})|\n\nUsing this feature you may"+" also search the extended fields (\"Metadata\") introduced with TiddlyWiki 2.1, e.g. use {{{priority:1"+"}}} to find all tiddlers with the priority field set to \"1\".\n\nYou may search a word in more than one"+" field. E.g. {{{!#Plugin}}} (or {{{title:tags:Plugin}}} in the \"long form\") finds tiddlers containin"+"g \"Plugin\" either in the title or in the tags (but does not look for \"Plugin\" in the text). \n\n!Boole"+"an Search\nThe Boolean Search is useful when searching for multiple words.\n|!What you want|!What you "+"type|!Example|\n|''All words'' must exist|List of words|{{{jonny jeremy}}} (or {{{jonny and jeremy}}}"+")|\n|''At least one word'' must exist|Separate words by ''or''|{{{jonny or jeremy}}}|\n|A word ''must "+"not exist''|Start word with ''-''|{{{-jonny}}} (or {{{not jonny}}})|\n\n''Note:'' When you specify two"+" words, separated with a space, YourSearch finds all tiddlers that contain both words, but not neces"+"sarily next to each other. If you want to find a sequence of word, e.g. '{{{John Brown}}}', you need"+" to put the words into quotes. I.e. you type: {{{\"john brown\"}}}.\n\nUsing parenthesis you may change "+"the default \"left to right\" evaluation of the boolean search. E.g. {{{not (jonny or jeremy)}}} finds"+" all tiddlers that contain neither \"jonny\" nor \"jeremy. In contrast to this {{{not jonny or jeremy}}"+"} (i.e. without parenthesis) finds all tiddlers that either don't contain \"jonny\" or that contain \"j"+"eremy\".\n\n!'Exact Word' Search\nBy default a search result all matches that 'contain' the searched tex"+"t. E.g. if you search for {{{Task}}} you will get all tiddlers containing 'Task', but also '~Complet"+"edTask', '~TaskForce' etc.\n\nIf you only want to get the tiddlers that contain 'exactly the word' you"+" need to prefix it with a '='. E.g. typing '=Task' will find the tiddlers that contain the word 'Tas"+"k', ignoring words that just contain 'Task' as a substring.\n\n!~CaseSensitiveSearch and ~RegExpSearch"+"\nThe standard search options ~CaseSensitiveSearch and ~RegExpSearch are fully supported by YourSearc"+"h. However when ''~RegExpSearch'' is on Filtered and Boolean Search are disabled.\n\nIn addition you m"+"ay do a \"regular expression\" search even with the ''~RegExpSearch'' set to false by directly enterin"+"g the regular expression into the search field, framed with {{{/.../}}}. \n\nExample: {{{/m[ae][iy]er/"+"}}} will find all tiddlers that contain either \"maier\", \"mayer\", \"meier\" or \"meyer\".\n\n!~JavaScript E"+"xpression Filtering\nIf you are familiar with JavaScript programming and know some TiddlyWiki interna"+"ls you may also use JavaScript expression for the search. Just enter a JavaScript boolean expression"+" into the search field, framed with {{{ { ... } }}}. In the code refer to the variable tiddler and e"+"valuate to {{{true}}} when the given tiddler should be included in the result. \n\nExample: {{{ { tidd"+"ler.modified > new Date(\"Jul 4, 2005\")} }}} returns all tiddler modified after July 4th, 2005.\n\n!Com"+"bined Search\nYou are free to combine the various search options. \n\n''Examples''\n|!What you type|!Res"+"ult|\n|{{{!jonny !jeremy -%football}}}|all tiddlers with both {{{jonny}}} and {{{jeremy}}} in its tit"+"les, but no {{{football}}} in content.|\n|{{{#=Task}}}|All tiddlers tagged with 'Task' (the exact wor"+"d). Tags named '~CompletedTask', '~TaskForce' etc. are not considered.|\n\n!Access Keys\nYou are encour"+"aged to use the access keys (also called \"shortcut\" keys) for the most frequently used operations. F"+"or quick reference these shortcuts are also mentioned in the tooltip for the various buttons etc.\n\n|"+"!Key|!Operation|\n|{{{Alt-F}}}|''The most important keystroke'': It moves the cursor to the search in"+"put field so you can directly start typing your query. Pressing {{{Alt-F}}} will also display the pr"+"evious search result. This way you can quickly display multiple tiddlers using \"Press {{{Alt-F}}}. S"+"elect tiddler.\" sequences.|\n|{{{ESC}}}|Closes the [[YourSearch Result]]. When the [[YourSearch Resul"+"t]] is already closed and the cursor is in the search input field the field's content is cleared so "+"you start a new query.|\n|{{{Alt-1}}}, {{{Alt-2}}},... |Pressing these keys opens the first, second e"+"tc. tiddler from the result list.|\n|{{{Alt-O}}}|Opens all found tiddlers.|\n|{{{Alt-P}}}|Toggles the "+"'Preview Text' mode.|\n|{{{Alt-'<'}}}, {{{Alt-'>'}}}|Displays the previous or next page in the [[Your"+"Search Result]].|\n|{{{Return}}}|When you have turned off the 'as you type' search mode pressing the "+"{{{Return}}} key actually starts the search (as does pressing the 'search' button).|\n\n//If some of t"+"hese shortcuts don't work for you check your browser if you have other extensions installed that alr"+"eady \"use\" these shortcuts.//";config.shadowTiddlers["YourSearch Options"]="|>|!YourSearch Options|\n|>|<<option chkUseYourSearch>> Use 'Your Search'|\n|!|<<option chkPreviewText"+">> Show Text Preview|\n|!|<<option chkSearchAsYouType>> 'Search As You Type' Mode (No RETURN required"+" to start search)|\n|!|Default Search Filter:<<option chkSearchInTitle>>Title ('!') <<option chk"+"SearchInText>>Text ('%') <<option chkSearchInTags>>Tags ('#') <<option chkSearchExtendedFiel"+"ds>>Extended Fields<html><br><font size=\"-2\">The fields of a tiddlers that are searched when you don"+"'t explicitly specify a filter in the search text <br>(Explictly specify fields using one or more '!"+"', '%', '#' or 'fieldname:' prefix before the word/text to find).</font></html>|\n|!|Number of items "+"on search result page: <<option txtItemsPerPage>>|\n|!|Number of items on search result page with pre"+"view text: <<option txtItemsPerPageWithPreview>>|\n";config.shadowTiddlers["YourSearchStyleSheet"]="/***\n!~YourSearchResult Stylesheet\n***/\n/*{{{*/\n.yourSearchResult {\n\tposition: absolute;\n\twidth: 800"+"px;\n\n\tpadding: 0.2em;\n\tlist-style: none;\n\tmargin: 0;\n\n\tbackground: #ffd;\n\tborder: 1px solid DarkGra"+"y;\n}\n\n/*}}}*/\n/***\n!!Summary Section\n***/\n/*{{{*/\n.yourSearchResult .summary {\n\tborder-bottom-width:"+" thin;\n\tborder-bottom-style: solid;\n\tborder-bottom-color: #999999;\n\tpadding-bottom: 4px;\n}\n\n.yourSea"+"rchRange, .yourSearchCount, .yourSearchQuery {\n\tfont-weight: bold;\n}\n\n.yourSearchResult .summary ."+"button {\n\tfont-size: 10px;\n\n\tpadding-left: 0.3em;\n\tpadding-right: 0.3em;\n}\n\n.yourSearchResult .summa"+"ry .chkBoxLabel {\n\tfont-size: 10px;\n\n\tpadding-right: 0.3em;\n}\n\n/*}}}*/\n/***\n!!Items Area\n***/\n/*{{{*"+"/\n.yourSearchResult .marked {\n\tbackground: none;\n\tfont-weight: bold;\n}\n\n.yourSearchItem {\n\tmargin-to"+"p: 2px;\n}\n\n.yourSearchNumber {\n\tcolor: #808080;\n}\n\n\n.yourSearchTags {\n\tcolor: #008000;\n}\n\n.yourSearc"+"hText {\n\tcolor: #808080;\n\tmargin-bottom: 6px;\n}\n\n/*}}}*/\n/***\n!!Footer\n***/\n/*{{{*/\n.yourSearchFoote"+"r {\n\tmargin-top: 8px;\n\tborder-top-width: thin;\n\tborder-top-style: solid;\n\tborder-top-color: #999999;"+"\n}\n\n.yourSearchFooter a:hover{\n\tbackground: none;\n\tcolor: none;\n}\n/*}}}*/\n/***\n!!Navigation Bar\n***/"+"\n/*{{{*/\n.yourSearchNaviBar a {\n\tfont-size: 16px;\n\tmargin-left: 4px;\n\tmargin-right: 4px;\n\tcolor: bla"+"ck;\n\ttext-decoration: underline;\n}\n\n.yourSearchNaviBar a:hover {\n\tbackground-color: none;\n}\n\n.yourSe"+"archNaviBar .prev {\n\tfont-weight: bold;\n\tcolor: blue;\n}\n\n.yourSearchNaviBar .currentPage {\n\tcolor: #"+"FF0000;\n\tfont-weight: bold;\n\ttext-decoration: none;\n}\n\n.yourSearchNaviBar .next {\n\tfont-weight: bold"+";\n\tcolor: blue;\n}\n/*}}}*/\n";config.shadowTiddlers["YourSearchResultTemplate"]="<!--\n{{{\n-->\n<span macro=\"yourSearch if found\">\n<!-- The Summary Header ============================"+"================ -->\n<table class=\"summary\" border=\"0\" width=\"100%\" cellspacing=\"0\" cellpadding=\"0\">"+"<tbody>\n <tr>\n\t<td align=\"left\">\n\t\tYourSearch Result <span class=\"yourSearchRange\" macro=\"yourSearc"+"h itemRange\"></span>\n\t\t of <span class=\"yourSearchCount\" macro=\"yourSearch count\"></span>\n"+"\t\tfor <span class=\"yourSearchQuery\" macro=\"yourSearch query\"></span>\n\t</td>\n\t<td class=\"yourSea"+"rchButtons\" align=\"right\">\n\t\t<span macro=\"yourSearch chkPreviewText\"></span><span class=\"chkBoxLabel"+"\">preview text</span>\n\t\t<span macro=\"yourSearch newTiddlerButton\"></span>\n\t\t<span macro=\"yourSearch openAllButton\"></span>\n\t\t<span macro=\"yourSearch lin"+"kButton 'YourSearch Options' options 'Configure YourSearch'\"></span>\n\t\t<span macro=\"yourSearch linkB"+"utton 'YourSearch Help' help 'Get help how to use YourSearch'\"></span>\n\t\t<span macro=\"yourSearch clo"+"seButton\"></span>\n\t</td>\n </tr>\n</tbody></table>\n\n<!-- The List of Found Tiddlers ================="+"=========================== -->\n<div id=\"yourSearchResultItems\" itemsPerPage=\"25\" itemsPerPageWithPr"+"eview=\"10\"></div>\n\n<!-- The Footer (with the Navigation) ==========================================="+"= -->\n<table class=\"yourSearchFooter\" border=\"0\" width=\"100%\" cellspacing=\"0\" cellpadding=\"0\"><tbody"+">\n <tr>\n\t<td align=\"left\">\n\t\tResult page: <span class=\"yourSearchNaviBar\" macro=\"yourSearch naviBar"+"\"></span>\n\t</td>\n\t<td align=\"right\"><span macro=\"yourSearch version\"></span>, <span macro=\"yourSearc"+"h copyright\"></span>\n\t</td>\n </tr>\n</tbody></table>\n<!-- end of the 'tiddlers found' case ========="+"================================== -->\n</span>\n\n\n<!-- The \"No tiddlers found\" case ================="+"========================== -->\n<span macro=\"yourSearch if not found\">\n<table class=\"summary\" border="+"\"0\" width=\"100%\" cellspacing=\"0\" cellpadding=\"0\"><tbody>\n <tr>\n\t<td align=\"left\">\n\t\tYourSearch Resu"+"lt: No tiddlers found for <span class=\"yourSearchQuery\" macro=\"yourSearch query\"></span>.\n\t</td>\n\t<t"+"d class=\"yourSearchButtons\" align=\"right\">\n\t\t<span macro=\"yourSearch newTiddlerButton\"></span>\n\t\t<span macro=\"yourSearch linkButton 'YourSearch Options'"+" options 'Configure YourSearch'\"></span>\n\t\t<span macro=\"yourSearch linkButton 'YourSearch Help' help"+" 'Get help how to use YourSearch'\"></span>\n\t\t<span macro=\"yourSearch closeButton\"></span>\n\t</td>\n <"+"/tr>\n</tbody></table>\n</span>\n\n\n<!--\n}}}\n-->\n";config.shadowTiddlers["YourSearchItemTemplate"]="<!--\n{{{\n-->\n<span class='yourSearchNumber' macro='foundTiddler number'></span>\n<span class='yourSea"+"rchTitle' macro='foundTiddler title'/></span> - \n<span class='yourSearchTags' macro='found"+"Tiddler field tags 50'/></span>\n<span macro=\"yourSearch if previewText\"><div class='yourSearchText' macro='fo"+"undTiddler field text 250'/></div></span>\n<!--\n}}}\n-->";config.shadowTiddlers["YourSearch"]="<<tiddler [[YourSearch Help]]>>";config.shadowTiddlers["YourSearch Result"]="The popup-like window displaying the result of a YourSearch query.";config.macros.search.handler=_109;var _195=function(){if(config.macros.search.handler!=_109){alert("Message from YourSearchPlugin:\n\n\nAnother plugin has disabled the 'Your Search' features.\n\n\nYou may "+"disable the other plugin or change the load order of \nthe plugins (by changing the names of the tidd"+"lers)\nto enable the 'Your Search' features.");}};setTimeout(_195,5000);abego.YourSearch.getStandardRankFunction=function(){return _bb;};abego.YourSearch.getRankFunction=function(){return abego.YourSearch.getStandardRankFunction();};abego.YourSearch.getCurrentTiddler=function(){return _f4;};abego.YourSearch.closeResult=function(){_e3();};abego.YourSearch.getFoundTiddlers=function(){return _b1;};abego.YourSearch.getQuery=function(){return _b2;};abego.YourSearch.onShowResult=function(_196){highlightHack=_b2?_b2.getMarkRegExp():null;if(!_196){_f5.setItems(_b5());}if(!_dd){_dd=createTiddlyElement(document.body,"div",_da,"yourSearchResult");}else{if(_dd.parentNode!=document.body){document.body.appendChild(_dd);}}_fe();highlightHack=null;};})();}
//%/
/***
|!''Name:''|!easyFormat|
|''Description:''|the format command format selection according to your choice|
|''Version:''|0.1.0|
|''Date:''|13/01/2007|
|''Source:''|[[TWkd|http://yann.perrin.googlepages.com/twkd.html#easyFormat]]|
|''Author:''|[[Yann Perrin|YannPerrin]]|
|''License:''|[[BSD open source license]]|
|''~CoreVersion:''|2.x|
|''Browser:''|Firefox 1.0.4+; Firefox 1.5; InternetExplorer 6.0|
|''Requires:''|@@color:red;''E.A.S.E''@@|
***/
//{{{
config.commands.format = new TWkd.Ease('Format','format selection accordingly to chosen mode');
config.commands.format.addMode({
name:'Bold',
tooltip:'turns selection into bold text',
operation:function(){
config.commands.format.putInPlace("''"+TWkd.context.selection.content+"''",TWkd.context.selection);
}
});
config.commands.format.addMode({
name:'Italic',
tooltip:'turns selection into italic text',
operation:function(){
config.commands.format.putInPlace("//"+TWkd.context.selection.content+"//",TWkd.context.selection);
}
});
config.commands.format.addMode({
name:'Underlined',
tooltip:'turns selection into underlined text',
operation:function(){
config.commands.format.putInPlace("__"+TWkd.context.selection.content+"__",TWkd.context.selection);
}
});
config.commands.format.addMode({
name:'Strikethrough',
tooltip:'turns selection into striked text',
operation:function(){
config.commands.format.putInPlace("--"+TWkd.context.selection.content+"--",TWkd.context.selection);
}
});
config.commands.format.addMode({
name:'Superscript',
tooltip:'turns selection into superscript',
operation:function(){
config.commands.format.putInPlace("^^"+TWkd.context.selection.content+"^^",TWkd.context.selection);
}
});
config.commands.format.addMode({
name:'Subscript',
tooltip:'turns selection into subscript',
operation:function(){
config.commands.format.putInPlace("~~"+TWkd.context.selection.content+"~~",TWkd.context.selection);
}
});
config.commands.format.addMode({
name:'Highlight',
tooltip:'highlight selection',
operation:function(){
config.commands.format.putInPlace("@@"+TWkd.context.selection.content+"@@",TWkd.context.selection);
}
});
//}}}
//{{{
/*
*what it's for: I needed to customize newTiddler macro to correctly open up a tiddler with the template EasyEdit+Template. This plugin defines the newEasyEdit macro, which can be called with an EasyEdit+ template using the standard call structure of the newTiddler macro.
*requirements: this plugin requires EasyEdit+ and an EasyEdit+ template (an edit template with the easyEdit macro invoked)
*/
config.macros.newEasyEdit=jQuery.extend(true, {}, config.macros.newTiddler);
config.macros.newEasyEdit.onClickNewTiddler=function(){
Popup.remove() //in the calling element was in a popup
var title = this.getAttribute("newTitle");
var params = this.getAttribute("params");
var tags = params ? params.split("|") : [];
var focus = this.getAttribute("newFocus");
var template = this.getAttribute("newTemplate");
var customFields = this.getAttribute("customFields");
if(!customFields && !store.isShadowTiddler(title))
customFields = String.encodeHashMap(config.defaultCustomFields);
story.displayTiddler(null,title,template,false,null,null);
var tiddlerElem = story.getTiddler(title);
if(customFields)
story.addCustomFields(tiddlerElem,customFields);
var text = this.getAttribute("newText");
if(typeof text == "string" && story.getTiddlerField(title,"text"))
var EEiframe=jQuery(tiddlerElem).find('#EasyEditiframe')
jQuery(EEiframe).contents().find('body').empty()
jQuery(EEiframe).contents().find('body').append(text)
for(var t=0;t<tags.length;t++)
story.setTiddlerTag(title,tags[t],+1);
story.focusTiddler(title,focus);
return false;
};
//}}}
//{{{
/*
defines a "reload" command, which fetches the current tiddler from a remote source (defined by config.options.txtReloadURL) using the LoadTiddlers plugin. This is used in goljanpathology.tiddlyspot.com to reload sections that have been screwed up by the user when annotating.
*/
config.options.txtReloadURL="http://goljanpathology.tiddlyspot.com";
config.commands.reload = {
type: "popup",
text: "reload",
tooltip: "sync to a fresh version of this section (undo all annotations)",
handlePopup: function(popup, title) {
wikify('Click below to get a fresh\n version of this section,\n undoing all annotations:\n',popup);
wikify('<<loadTiddlers "label:reload from server" "prompt:import a fresh version of this section from '+config.options.txtReloadURL+', undoing all annotations" "tiddler:'+title+'" '+config.options.txtReloadURL+' force noreport>>',popup);
}
}
//}}}
<<options>>
<<loadTiddlers "label:reload" "prompt:import a fresh version of this section from the site" "tiddler:1.I.A.Hypoxia" http://goljanpathology.tiddlyspot.com force noreport>>
<<saveChanges save "tooltip">>
<<tiddler tiddlyimporttest.txt#[[01 Cell Injury]]>>
<<tiddler ShowPopupAbove with: [[BOX 1-1 CLINICAL ENZYMOLOGY]] [[Try this]] [[show this tiddler in a popup]] [[button]]>>
<<tag CHAPTERS>>
<<tag story>>
[[ASplugin]]
<html>▬̟</html>
<html>▬̳</html>
<html>heavy minus sign: ❎</html>
<html>✕̬</html>
<html>✕͝</html>
<html>✕̬</html>
<html>❎</html>
<html>✕̬</html>
<html>✕̬</html>
<html>✕̬</html>
<html>✕̬</html>
<html>✕⃞</html>
<<storyViewer CHAPTERS>>
<<snapshot print id:ask>>
<html><a href="javascript:;">SubMenu</a></html>
<html><a href="javascript:;" title="SubMenu - AS, February 26, 2011 9:11:00 PM EST" class="tiddlyLink tiddlyLinkExisting" refresh="link" tiddlylink="SubMenu">SubMenu</a>
<script>createTiddlyText(createTiddlyLink(jQuery('<div></div>')[0],'SubMenu',true),'SubMenu' );</script></html><script>createTiddlyText(createTiddlyLink(jQuery('<div></div>')[0],'SubMenu',true),'SubMenu' );</script>
<<tag [[01 Cell Injury]] [[Chapter 1]]>>
<<tiddler ShowPopup with: [[BOX 1-1 CLINICAL ENZYMOLOGY]] [[Try this]] [[show this tiddler in a popup]] [[button]]>>
<html><span macro="tiddler ShowPopup with: [[Figure 1-1]] [[this is a popup]] [[show this tiddler in a popup]] [[button]]"></span></html>
<<tagging [[01 Cell Injury]]>>
<<relatedTiddlers CHAPTERS>>
//{{{
config.options.txtEasyEditorButtons='removeformat,separator,separator,bold,italic,underline,strikethrough,separator,fontname,fontsize,separator,separator,separator,justifyleft,justifycenter,justifyright,justifyfull,separator,separator,separator,insertparagraph,insertunorderedlist,insertorderedlist,inserthorizontalrule,separator,separator,forecolor';
//config.options.txtEasyEditorButtons='hilitecolor|hightlight|this is a tooltip|yellow';
//}}}
//{{{
//===========================================================================================
//disable edit mode by default (can change this option in SubMenu)
config.options.chkEditMode=false;
//===========================================================================================
//modifications to backstage area:
config.tasks.myTab2 = {
text: "functions",
tooltip: "various special functions",
content: "<<tiddler ASbackstage>>"
};
config.backstageTasks.push("myTab2");
config.messages.backstage.prompt="CAUTION: If you don't know what these things do, don't mess around!";
config.messages.backstage.open.text=' ';
config.messages.backstage.close.text=' ';
//===========================================================================================
//by default, the username is "user", only "admin" is allowed to administer and make certain changes
defaultusername="user";
config.options.adminUserName="admin";
config.options.txtUserName=defaultusername;
// the username is switched to adminUserName when the backstage button is clicked to eliminate the need for logging in,
// then switched back to the default after clicking the backstage hide buttn:
// MAKE SURE TO COMMENT THIS OUT WHEN PUBLISHING/DEPLOYING!!!
//hijack the backstage.show() and .hide() functions to switch username to admin and back again:
/*
backstage.show_old=backstage.show;
backstage.show=function(){
this.show_old.apply(this,arguments);
config.options.txtUserName=config.options.adminUserName;
};
backstage.hide_old=backstage.hide;
backstage.hide=function(){
this.hide_old.apply(this,arguments);
config.options.txtUserName=defaultusername;
};
*/
//===========================================================================================
co=config.options; //why didn't i think of this sooner?
config.options.chkSliderSearchPanel=false;
config.options.chkBackstage=false;
config.options["chkShowRightSidebar"]=false;
config.options.chkSaveBackups=true;
config.options["txtTweakerSortBy"]="created";
// set various search options
config.options.chkIncrementalSearch=false;
config.options["chkSearchAsYouType"]=false;
config.options["chkSearchAsYouType"]= false;
config.options["chkSearchByDate"]= false;
config.options["chkSearchExcludeTags"]= true;
config.options["chkSearchExtendedFields"]= false;
config.options["chkSearchFields"]= false;
config.options["chkSearchHighlight"]= true;
config.options["chkSearchInTags"]= false;
config.options["chkSearchInText"]= true;
config.options["chkSearchInTitle"]= true;
config.options["chkSearchList"]= true;
config.options["chkSearchListTiddler"]= true;
config.options["chkSearchOpenTiddlers"]= false;
config.options["chkSearchResultsOptions"]= false;
config.options["chkSearchShadows"]= false;
config.options["chkSearchTags"]= false;
config.options["chkSearchText"]= true;
config.options["chkSearchTitles"]= true;
config.options["chkSearchTitlesFirst"]= true;
config.options["chkUseYourSearch"]=false;
// set various story options
config.options["chkStoryAllowAdd"]= false;
config.options["chkStoryBottom"]= false;
config.options["chkStoryClose"]= true;
config.options["chkStoryFold"]= true;
config.options["chkStoryTop"]= true;
config.options["chkSaveStory"]= false;
config.options.txtFCKCustomConfigScript="fckeditor/editor/fckEditorCustomConfig.js";
config.animDuration=200; //animation duration in ms
config.options.chkDisableNonExistingWikiLinks=true; //disable linking to noncreated tiddlers
config.options.chkDisableWikiLinks=true;
config.options.chkAutoTagNewTags=true;
config.options.txtAutoTagNewTags="NOTES";
config.tiddlerTemplates[5]="EasyEdit+Template";DEFAULT_NEW_TEMPLATE=5; //specify default new template, used in TaggedTemplateTweak+
co.chkLooseLinks=true;
co.chkInsertTabs=true;
//==========================================================================================
// change default messages:
cm=config.macros;
cc=config.commands;
config.views.wikified.defaultText=""; // default text for new tiddlers
config.messages.overwriteWarning="A section named '%0' already exists. Choose OK to overwrite it";
config.messages.undefinedTiddlerToolTip="'%0' doesn't exist yet";
cm.permaview.prompt="Link to an URL that retrieves all the currently displayed sections";
cc.cancelTiddler.tooltip="undo changes";
cc.saveTiddler.tooltip="save changes";
cc.deleteTiddler.tooltip="delete this section";
cm.tagging.label="found %1:";
cm.tagging.labelNotTag="none found";
cm.tagging.tooltip="list of sections tagged with '$0'";
cm.search.prompt="search this file";
cm.search.failureMsg="nothing found matching %0";
cm.search.successMsg="%0 sections found matching %1";
config.messages.TemporaryWarning="'%0' ...temporary section";
config.messages.TemporarySummary="%0 temporary sections (such as search results) will not be saved";
config.commands.permalink.text="link";
//==========================================================================================
//make a couple of new macros
config.commands.closeTiddler.text="✕";
config.commands.closeOthers.text="✖";
//config.commands.collapseTiddler.text='▬';
config.commands.collapseTiddler.text='—';
//config.commands.collapseOthers.text='▬̳'
config.commands.collapseOthers.text='▬';
config.commands.expandTiddler.text='❑';
config.commands.editTiddler.text="✍";
config.macros.closeAll.label='✕ Close All';
config.macros.expandAll.text='▢ Expand All';
config.macros.collapseAll.text='▬ Collapse All';
config.commands.expandTiddler.tooltip="Expand this section"
config.commands.closeTiddler.tooltip="Close this section";
config.commands.collapseTiddler.tooltip="Collapse this section";
config.commands.collapseOthers.tooltip="Expand this section and collapse all others";
config.commands.closeOthers.tooltip="Close all other sections";
config.commands.permalink.tooltip="Permanent link to this section";
config.commands.snapshotPrintHere.tooltip="Open this section in a new window for printing";
config.macros.closeAll.prompt="Close all loaded sections";
config.macros.closeAllsymbol=jQuery.extend({},config.macros.closeAll);
config.macros.closeAllsymbol.label='✕';
config.macros.expandAll.tooltip="Expand all loaded sections";
config.macros.expandAllsymbol=jQuery.extend({},config.macros.expandAll);
config.macros.expandAllsymbol.text='❑'
config.macros.collapseAll.tooltip="Collapse all loaded sections";
config.macros.collapseAllsymbol=jQuery.extend({},config.macros.collapseAll);
config.macros.collapseAllsymbol.text='—';
config.commands.bottom={};
config.commands.bottom.handler=function(){
scrollTo(0,document.height);
};
config.commands.bottom.text="↓";
config.commands.bottom.tooltip="jump to bottom";
config.commands.top={}
config.commands.top.handler=function(){
scrollTo(0,0);
};
config.commands.top.text="↑";
config.commands.top.tooltip="jump to top";
//===========================================================================================
//change the way that the position is calculated to use jQuery's offset property, which gives the position relative to the document
findPosX_old=findPosX;
findPosY_old=findPosY;
/*
findPosX=function(el){
try{return jQuery(el).offset().left;}
catch(err){return findPosX_old(el);}
}
*/
findPosY=function(el){
try{return jQuery(el).offset().top}
catch(err){return findPosY_old(el)}
}
//===========================================================================================
//jump macro, adapted from HoverMenu plugin
config.macros.jump= {};
config.macros.jump.handler = function (place,macroName,params,wikifier,paramString,tiddler)
{
var label = (params[0] && params[0]!=".")? params[0]: 'jump';
var tooltip = (params[1] && params[1]!=".")? params[1]: 'jump to an open tiddler';
var top = (params[2] && params[2]=='top') ? true: false;
var btn =createTiddlyButton(place,label,tooltip,this.onclick);
if (top==true)
btn.setAttribute("top","true")
}
config.macros.jump.onclick = function(e)
{
if (!e) var e = window.event;
var theTarget = resolveTarget(e);
var top = theTarget.getAttribute("top");
var popup = Popup.create(this);
if(popup)
{
if(top=="true")
{createTiddlyButton(createTiddlyElement(popup,"li"),'Top ↑','Top of TW',config.macros.jump.top);
createTiddlyElement(popup,"hr");}
story.forEachTiddler(function(title,element) {
createTiddlyLink(createTiddlyElement(popup,"li"),title,true);
});
}
Popup.show(popup,false);
e.cancelBubble = true;
if (e.stopPropagation) e.stopPropagation();
return false;
}
config.macros.jump.top = function()
{
window.scrollTo(0,0);
}
//===========================================================================================
//change onclickTag() to make a new TAG button...also change some of the default text in the buttons:
config.views.wikified.tag.openAllText="open all";
config.views.wikified.tag.openAllTooltip="Open all of these sections"
config.views.wikified.tag.openTag="open %0";
config.views.wikified.tag.tooltip="Show sections tagged with '%0'";
function onClickTag(ev) {
var e = ev || window.event;
var popup = Popup.create(this);
addClass(popup,"taggedTiddlerList");
var tag = this.getAttribute("tag");
var title = this.getAttribute("tiddler");
if(popup && tag) {
var tagged = tag.indexOf("[")==-1 ? store.getTaggedTiddlers(tag) : store.filterTiddlers(tag);
var sortby = this.getAttribute("sortby");
if(sortby&&sortby.length) {
store.sortTiddlers(tagged,sortby);
}
var titles = [];
var li,r;
for(r=0;r<tagged.length;r++) {
//if(tagged[r].title != title)//this line is supposed to exclude the current tiddler from being displayed in the drop-down list, but let's leave it
titles.push(tagged[r].title);
}
if(titles.length==0){story.displayTiddler(this,tag); return false;};
var lingo = config.views.wikified.tag;
var h = createTiddlyLink(createTiddlyElement(popup,"li"),tag,false);
createTiddlyText(h,lingo.openTag.format([tag]));
if(titles.length > 0) {
createTiddlyElement(createTiddlyElement(popup,"li",null,"listBreak"),"div");
//sectionLI=createTiddlyElement(popup,"li",null,null,'tagging: ');
//createTiddlyElement(createTiddlyElement(popup,"li",null,"listBreak"),"div");
for(r=0; r<titles.length; r++) {
//newlink=createTiddlyLink(createTiddlyElement(popup,"li"),' ',false);
//create a Tag button with the "tag" being the title of the found tiddlers
createTagButton(createTiddlyElement(popup,"li"), titles[r], null, titles[r], config.views.wikified.tag.tooltip.format([titles[r]]))
}
createTiddlyElement(createTiddlyElement(popup,"li",null,"listBreak"),"div");
var openAll = createTiddlyButton(createTiddlyElement(popup,"li"),lingo.openAllText.format([tag]),lingo.openAllTooltip,onClickTagOpenAll);
openAll.setAttribute("tag",tag);
openAll.setAttribute("sortby",sortby);
} else {
//createTiddlyElement(popup,"li",null,"disabled",lingo.popupNone.format([tag]));
}
Popup.show();
e.cancelBubble = true;
if(e.stopPropagation) e.stopPropagation();
return false;
}
}
//===========================================================================================
//hijack onClickTagOpenAll() to collapse all tiddlers that are opened this way
onClickTagOpenAll_old=onClickTagOpenAll;
onClickTagOpenAll=function(){
var tiddlers = store.getTaggedTiddlers(this.getAttribute("tag"));
var t=config.commands.collapseTiddler.getCollapsedTemplate();
onClickTagOpenAll_old.apply(this,arguments);
for(i=0;i<tiddlers.length;i++){
var title=tiddlers[i].title;
var e=jQuery('div[tiddler=\"'+title+'\"] .toolbar')[0];
config.commands.collapseTiddler.display(title,t);
e.setAttribute("folded","true");
}
return false;
};
//===========================================================================================
//remove/disable core TW definition list formatter
var f=config.formatters[config.formatters.findByField("name","list")];
f.match="^(?:[\\*#]+)";
f.lookaheadRegExp=/^(?:(?:(\*)|(#))+)/mg;
//===========================================================================================
config.commands.switchEditMode={
handler : function(event,src,title){
var newTitle = story.saveTiddler(title)
if(newTitle)
story.displayTiddler(null,newTitle,DEFAULT_EDIT_TEMPLATE);
return false;
},
text : "✍",
tooltip : "switch edit mode"}
//===========================================================================================
//}}}