90981 ch 16.qxd 10/9/06 10:14 AM Page 389 CHAPTER 16 Diseases of the Liver and Biliary Tract This chapter begins with a review of the normal anatomy and physiology of the liver and biliary tract Diseases and disorders discussed include cirrhosis, hepatitis, alcoholic and metabolic liver disease, gallstones and other gallbladder disease, and cancers of the liver and biliary tract BACK TO BASICS • Liver Anatomy • Liver Function THE LIVER RESPONSE TO INJURY • Anatomic Patterns of Liver Injury • Functional Patterns of Liver Injury CIRRHOSIS • Anatomic Types of Cirrhosis • The Pathophysiology of Cirrhosis • Clinical Features of Cirrhosis VIRAL HEPATITIS • Clinicopathologic Syndromes • Hepatitis A Virus (HAV) Infection • Hepatitis B Virus (HBV) Infection • Hepatitis C Virus (HCV) Infection • Hepatitis D Virus (HDV) Infection • Hepatitis E Virus (HEV) Infection • The Anatomic Pathology of Hepatitis AUTOIMMUNE HEPATITIS LIVER ABSCESS TOXIC LIVER INJURY ALCOHOLIC LIVER DISEASE • Fatty Liver • Alcoholic Hepatitis • Alcoholic Cirrhosis INHERITED METABOLIC AND PEDIATRIC LIVER DISEASE • Hemochromatosis • Wilson Disease • Hereditary Alpha-1 Antitrypsin Deficiency • Neonatal Cholestasis, Biliary Atresia, and Hepatitis • Reye Syndrome DISEASE OF INTRAHEPATIC BILE DUCTS • Primary Biliary Cirrhosis • Primary Sclerosing Cholangitis CIRCULATORY DISORDERS TUMORS OF THE LIVER • Primary Carcinomas of the Liver • Cholangiocarcinoma DISEASES OF THE GALLBLADDER AND EXTRAHEPATIC BILE DUCTS • Diseases of the Gallbladder • Diseases of Extrahepatic Bile Ducts Learning Objectives After studying this chapter you should be able to: Trace the flow of blood through the liver Name the major functions of the liver Explain the enterohepatic circulation Name the major functional reactions of the liver to injury Explain the difference between conjugated and unconjugated bilirubin Name one cause of unconjugated hyperbilirubinemia and one of conjugated hyperbilirubinemia Define cirrhosis, and name the two most common causes Explain why cirrhosis causes portal hypertension Name two hemodynamic consequences of portal hypertension 10 Outline the main clinical manifestations of cirrhosis 11 Name several clinicopathologic syndromes associated with viral hepatitis 12 Contrast the mode of transmission and clinical course of hepatitis A and hepatitis B infection 389 90981 ch 16.qxd 390 13 14 15 16 17 18 19 10/9/06 10:14 AM Page 390 Part • Diseases of Organ Systems Name the most important epidemiologic fact about hepatitis C, and name the most common serious consequences of hepatitis C infection Name one common acute and one common chronic change induced in the liver by alcohol abuse Explain the difference between primary biliary cirrhosis and sclerosing cholangitis Name the liver condition most commonly associated with hepatocellular carcinoma Name the two major categories of gallstones, and know which is the most common Name several risk factors that favor the formation of gallstones Discuss some of the most common causes of extrahepatic bile duct obstruction Key Terms and Concepts VIRAL HEPATITIS • viral hepatitis • carrier state • chronic viral hepatitis • hepatitis A virus (HAV) • hepatitis B virus (HBV) • hepatitis C virus (HCV) BACK TO BASICS • portal vein • hepatocytes • bile duct • bile • bile acids • bilirubin • unconjugated bilirubin • conjugated bilirubin • jaundice • cholestasis ALCOHOLIC LIVER DISEASE • fatty liver INHERITED METABOLIC AND PEDIATRIC LIVER DISEASE • neonatal cholestasis THE LIVER RESPONSE TO INJURY • hepatitis • cirrhosis • hepatic failure DISEASE OF INTRAHEPATIC BILE DUCTS • primary biliary cirrhosis TUMORS OF THE LIVER • hepatocellular carcinoma CIRRHOSIS • portal cirrhosis • biliary cirrhosis • portal hypertension DISEASES OF THE GALLBLADDER AND EXTRAHEPATIC BILE DUCTS • cholelithiasis • cholecystitis Two of every three deaths are premature; they are related to the loafer’s heart, smoker’s lung and drinker’s liver DR THOMAS J BASSLER, PATHOLOGIST; QUOTED BY JAMES FIXX (1932–1984), IN THE COMPLETE BOOK OF RUNNING (Random House, 1977) BACK TO BASICS The liver regulates the composition of blood by disposing of waste products (bilirubin, for example), converting substances from one form into another (glycogen into glucose and vice versa), secreting substances into the intestines (bile and cholesterol), and producing plasma proteins (albumin, coagulation factors, and others) The anatomy of the liver, portal venous system, and bile ducts is illustrated in Figure 16-1 Nutrients absorbed by the intestine not enter the general circula- tion directly; instead they flow first to the liver via the portal vein The vein gains its name from the fact that the liver is a gate (a portal or doorway) through which blood must pass before entering the general circulation This “gate” effect is unique in human anatomy: venous blood goes from one capillary system (the intestine), is collected into a large vein (portal), and passes through a second capillary system (the liver) before entering the general circulation The liver also receives arterial blood from the hepatic artery, which merges with portal blood before flowing through the hepatic vein into the inferior vena cava 90981 ch 16.qxd 10/9/06 10:14 AM Page 391 Chapter 16 • Diseases of the Liver and Biliary Tract 391 Inferior vena cava Left hepatic vein Right hepatic vein Liver Hepatic duct Cystic duct Hepatic artery Portal vein Common bile duct A Plates of hepatocytes Bile canaliculi Central vein To hepatic vein, then to inferior vena cava Blood mixes in sinusoids Bile duct Portal triad Portal vein from bowel Hepatic artery from aorta B Figure 16-1 The liver, portal venous system, and bile ducts A, The liver and biliary system B, The hepatic lobule Blood flows into the central vein from branches of the portal vein and hepatic artery clustered in portal triads at the edge of the lobule Bile flows in the opposite direction— from the interior of the lobule to bile ducts in the portal triads 90981 ch 16.qxd 392 10/9/06 10:14 AM Page 392 Part • Diseases of Organ Systems The circulation of blood through the intestines and liver is unique in human anatomy: blood from one capillary system, the intestinal, flows into another capillary system, the hepatic, before returning to the heart LIVER ANATOMY Upon entering the portal circulation, blood and freshly absorbed nutrients are brought into close contact with the main functional cells (parenchyma) of the liver (hepatocytes) Liver cells are formed into plates one or two cells thick that are sandwiched between large venous capillaries (hepatic sinusoids) Hepatic sinusoids have no basement membrane and are therefore much more permeable than other capillaries are, so that even large protein and lipid molecules cross freely Venous sinusoid walls contain fixed macrophages known as Kupffer cells, which, unlike other macrophages, not move about but remain in place to filter portal blood The plates of hepatic cells are arranged into a hepatic lobule In the middle of each lobule is a central vein surrounded by hepatocytes The corners of each lobule are defined by several portal triads consisting of 1) a branch of the hepatic artery bringing blood from the aorta, 2) a portal vein carrying blood from the GI tract, and 3) a small bile duct that carries bile out of the liver Blood entering the lobule from the hepatic artery and portal vein flows into venous sinusoids, percolates through hepatic plates, and is collected in the central vein for delivery to the general circulation The liver is a large gland that secretes bile into the intestines Bile is a mixture of metabolic waste and bile acids, which emulsify (make water soluble) dietary fat so it can be absorbed by the intestinal mucosa Bile is excreted by hepatocytes into a network of small intrahepatic bile ducts that carry it out of the liver and into the common bile duct (hepatic duct), which connects to the intestine at the ampulla of Vater in the duodenum A reserve of bile is held in the gallbladder and discharged after meals Figure 16-2 illustrates that much of the bile acid excreted into the intestine is reabsorbed by the small bowel and sent back to the liver for reuse, a process known as the enterohepatic circulation Only a small amount of bile acid finds its way into feces LIVER FUNCTION As is outlined in Table 16-1, the liver has five main functions: 1) detoxification and excretion of metabolic waste, drugs, and hormones; 2) lipid and carbohydrate metabolism; 3) protein synthesis; 4) conjugation and excretion of bilirubin; and 5) synthesis and excretion of bile acids The liver clears blood of endogenous metabolic waste (especially bilirubin and ammonia), chemicals and toxins (especially drugs), and hormones (especially estrogen) It does so by excreting them into bile, as it does with bilirubin, or converting them into something not harmful, as it does by converting ammonia to urea The liver modulates blood glucose concentration by storing glucose as glycogen and reconverts and excretes it on demand Additionally, the liver synthesizes triglycerides and cholesterol and, when necessary, burns fat and excretes the ketones produced by the process Ketones are an acidic by-product of fat metabolism that accounts for the acidosis (ketosis) that occurs when diabetic patients are without insulin and cannot burn glucose, and the liver must burn fat to produce energy (Chapter 17) The liver produces virtually all plasma proteins except antibodies (immunoglobulins), which are made by B lymphocytes of the immune system Plasma protein consists of albumin, alpha and beta globulins—all made by the liver—and gamma globulins (immunoglobulins, or antibodies, made by lymphocytes of the immune system, Chapter 8) The most abundant liver protein is albumin, which forms about three fourths of plasma protein and provides most of the osmotic pressure of plasma (Chapter 5) that holds water in blood Other proteins produced by the liver include clotting factors (Chapter 11) and specialized proteins for fat (and transport of fat, hormones, iron, and other substances The liver excretes bilirubin into bile ducts, which carry it to the bowel Bilirubin is an intensely yellow pigment, most of which is produced in the spleen from the hemoglobin of old red blood cells the spleen has removed from the circulation This new bilirubin is not water soluble and must be attached to a protein for transport to the liver, where it is made water soluble and excreted in bile In the liver, bilirubin is joined (conjugated) to glucuronide to make conjugated bilirubin, which is water soluble and can be excreted in bile Before reaching the liver, the water-insoluble bilirubin is called unconjugated bilirubin Increased blood bilirubin (of either type) causes jaundice (icterus), a yellow discoloration of skin and sclera that is a hallmark of increased blood bilirubin Bacteria in the bowel convert bilirubin into urobilinogen, a compound that gives feces its brown color Patients with jaundice usually have pale stools owing to a lack of urobilinogen However, some urobilinogen is produced directly by the liver, secreted into blood, and 90981 ch 16.qxd 10/9/06 10:14 AM Page 393 Chapter 16 • Diseases of the Liver and Biliary Tract 393 Liver Bile Reabsorption and reexcretion Common bile duct Portal vein Gallbladder Figure 16-2 The enterohepatic circulation Bile acids are secreted into bile, absorbed back into blood by the intestine, and recirculated via the portal vein for remetabolism by the liver Small intestine Feces Table 16-1 Liver Functions Metabolic Task Hepatocyte Actions Detoxification and drug metabolism • Chemical alteration and excretion of hormones and drugs • Production and excretion of urea and other compounds that are less toxic than the parent compound Lipid and carbohydrate metabolism • • • • • • Protein synthesis • Synthesis and secretion into blood of albumin, transport proteins and blood coagulation (clotting) factors Conjugation and excretion of bilirubin • Conjugation of bilirubin with glucuronide and excretion of it into bile ducts Synthesis and excretion of bile acids • Synthesis of bile acids by liver cells and secretion of them into bile ducts Conversion of glucose to glycogen and fat Production of glucose from glycogen and other compounds Secretion of glucose into blood Synthesis and secretion of triglyceride and cholesterol into blood Excretion of cholesterol into bile Production of ketones from fatty acid 90981 ch 16.qxd 394 10/9/06 10:14 AM Page 394 Part • Diseases of Organ Systems excreted into urine, giving urine its faint amber color Jaundiced patients may have dark urine because of increased urobilinogen The liver produces and excretes bile acids Bile acids, the main constituent of bile, emulsify fat like soap does grease, solubilizing it for absorption Bile acids are produced by the liver from cholesterol, and bile acid excretion is the main way by which the body rids itself of cholesterol However, most bile acids and the choles- terol they contain are reabsorbed by the intestinal mucosa and returned to blood (enterohepatic circulation) The enterohepatic circulation is, therefore, very important in cholesterol metabolism Most cholesterol absorbed from the intestine is not from diet but from reabsorption of bile acids New drugs lower blood cholesterol by blocking intestinal absorption of cholesterol Obstruction of bile excretion is referred to as cholestasis ANATOMIC PATTERNS OF LIVER INJURY MAJOR DETERMINANTS OF DISEASE • The metabolic consequences of liver disease are serious and include: – Toxic accumulations of: metabolic waste (especially ammonia and bilirubin) drugs and toxins endogenous hormones (especially estrogen) – Bleeding, associated with a deficiency of coagulation factors – Edema, associated with a deficiency of plasma albumin – Failure to absorb intestinal fat because of a deficiency of bile acids • Viral hepatitis is a common contagious disease • Cirrhosis is the final endpoint for many liver diseases • Portal hypertension is the most important consequence of cirrhosis and can be associated with liver failure and severe hemorrhage • Stones often form in the gallbladder and may pass into and obstruct the bile duct ᭿ ᭿ ᭿ The injury to liver prompts one of four consequences: inflammation, degeneration, necrosis, and fibrosis • Inflammation: Inflammation of the liver is termed hepatitis, most of which is caused by virus infections • Degeneration: Hepatocytes may undergo hydropic (watery) or fatty degeneration (Chapter 2) in response to toxic or autoimmune injury For example, alcohol abuse typically causes fatty degeneration, which can proceed to injury that is more serious if alcohol abuse continues • Necrosis: Liver cells may die as blocks of tissue (infarcts, Chapter 2) or as single cells In some types of diffuse hepatic injuries, such as viral hepatitis and chronic alcohol injury, individual liver cells die one by one, becoming shrunken, dead cells known as Councilman bodies • Fibrosis: Scarring can occur as a result of severe hepatic injury Cirrhosis (discussed in detail below) is a patterned, permanent scarring (fibrosis) of the entire liver from long-standing, severe injury that destroys the normal architecture and replaces it with scar tissue FUNCTIONAL PATTERNS OF LIVER INJURY The Liver Response to Injury The direct metabolic consequences of hepatic injury are: The liver responds remarkably well to injury—it has enormous functional reserve and must suffer a marked decline of capacity before becoming symptomatic However, because normal liver function is so crucial in metabolism, liver disease looms large in human illness Laboratory evaluation of blood is critical in the diagnosis and management of liver disease The nearby Lab Tools box lists and describes the most common lab tests • Jaundice: a yellow discoloration of skin and sclerae (Fig 16-3) caused by an excess of blood bilirubin • Cholestasis: an accumulation of bile acids and cholesterol in blood when there is obstruction of bile flow inside or outside of the liver • Hepatic failure: the loss of hepatic metabolic function severe enough to cause clinical symptoms Each of these consequences may be associated with widespread ill effect on the body 90981 ch 16.qxd 10/9/06 10:14 AM Page 395 Chapter 16 • Diseases of the Liver and Biliary Tract 395 LAB TOOLS Liver Function Tests The most useful laboratory tests for liver function are: • Enzymes: The liver is packed with enzymes In liver disease these enzymes are washed into blood, where they are easily measured Even mild liver-cell injury can cause minor increases in levels of liver enzymes Elevation of lactic dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) suggests hepatic cellular damage Alkaline phosphatase levels also may be increased in liver disease, but they tend to rise highest in bile duct diseases Red blood cells contain some of these enzymes, and in vitro damage (hemolysis) to red cells during specimen collection or handling can cause misleading enzyme level increases • Bilirubin: The liver metabolizes and excretes bilirubin into the bile ducts If hemolytic disease has been excluded, increased levels of blood bilirubin usually indicate at least moderate liver disease or bile duct disease • Proteins: The liver makes albumin and many other plasma proteins Low levels of plasma albumin and blood coagulation factors are characteristic of moderate to serious liver disease • Coagulation tests: The liver makes most of the coagulation proteins (factors), and liver disease can cause abnormal (prolonged) prothrombin time and partial thromboplastin time • Hepatitis virus antigens and antibodies: Each type of hepatitis virus is distinguished by characteristic patterns of virus antigens and antibodies in blood • Autoimmune antibodies: Antimitochondrial antibodies in blood are characteristic of primary biliary cirrhosis; antismooth muscle antibodies are characteristic of chronic autoimmune hepatitis • defective liver functioning (hepatic jaundice), such as occurs with viral hepatitis, drug interference with liver function, or cirrhosis • biliary obstruction (posthepatic jaundice), such as occurs when pancreatic cancer occludes the common bile duct Figure 16-3 Scleral icterus of jaundice Jaundice and Cholestasis Jaundice usually becomes visible when blood bilirubin level is Ͼ2 mg/dL (normal Ͻ1.2 mg/dL) As is illustrated in Figure 16-4, jaundice can be caused by three conditions: • the presence of excessive amounts of bilirubin (prehepatic jaundice), such as accompanies red cell destruction in hemolytic anemia Prehepatic jaundice causes an increase in blood of water-insoluble unconjugated bilirubin The most common serious cause of increased amounts of unconjugated bilirubin in blood is hemolytic anemia, such as sickle cell disease (Chapter 11) Increased unconjugated bilirubin can also occur when there is hepatic malfunction For newborns unconjugated hyperbilirubinemia is especially dangerous, because it is toxic to the underdeveloped brain Because the immature livers of premature infants are unable to conjugate bilirubin effectively, during the first several weeks of life a marked increase of unconjugated bilirubin may cause kernicterus (from German: kern, nucleus, and icterus, jaundice), a severe neurologic condition resulting from toxic deposits of water-insoluble, unconjugated bilirubin in the brain (Chapter 7) However, the most common cause of increased unconjugated bilirubin in blood is Gilbert syndrome (pronounced jeel-bear), a very common and harmless condition associated with a mild increase of unconjugated bilirubin that is the result of a genetic enzyme defi- 90981 ch 16.qxd 396 10/9/06 10:14 AM Page 396 Part • Diseases of Organ Systems Major cause: Red blood cell • Hemolysis Macrophage Hemoglobin Bilirubin Circulating bilirubin A Prehepatic jaundice (unconjugated hyperbilirubinemia) Cirrhosis Metastatic cancer Major causes: • Viral hepatitis • Toxins • Therapeutic drugs • Cirrhosis • Neoplasms B Hepatic jaundice (unconjugated or conjugated hyperbilirubinemia) Bile duct Gallbladder Stones Major causes: Gallstones in bile ducts Pancreatic cancer C Posthepatic jaundice (conjugated hyperbilirubinemia) ciency, which is usually detected accidentally while the patient is being seen for an unrelated illness or when the patient has been fasting for 12 hours or more A similar genetic syndrome causing increased conjugated bilirubin is the Dubin-Johnson syndrome Jaundice associated with hepatic disorders (hepatic jaundice) may cause an increase in blood of either unconjugated or conjugated bilirubin, because interference can occur either before or after conjugation in the liver Jaundice resulting from bile duct obstruction (posthepatic jaundice) is characterized by increased watersoluble, conjugated bilirubin in blood because by the time bilirubin enters hepatic ducts all of it is conjugated, and obstruction forces conjugated bilirubin out of the ducts and into blood Gallstones and pancreatic cancer are the two most common causes of duct obstruction Cholestasis is usually accompanied by jaundice and sometimes by severe pruritus (itching) because of the deposition of bile acids in the skin Cholestasis may result from primary liver disease, drug interference with bile secretion, pregnancy, and a variety of other conditions Because bile is the means by which the body rids itself of excess cholesterol, blood cholesterol levels may become markedly elevated and associated with yellow deposits of cholesterol in skin (xanthomas) Because bile duct epithelium is rich in alkaline phosphatase, a characteristic laboratory finding is marked increase of blood alkaline phosphatase levels, whereas levels of other liver enzymes are usually normal or only mildly increased Hepatic Failure Hepatic failure is the most severe consequence of liver disease—most patients die within a few weeks or months It may follow sudden injury, as in sudden, severe viral hepatitis (fulminant hepatitis), or it may be the result of chronic injury, as with chronic hepatitis or chronic alcoholism About 90% of hepatic function must be destroyed before failure occurs The clinical features of hepatic failure are: • Jaundice because of failure to excrete bilirubin • Ascites because of increased portal pressure and low blood osmotic pressure • Fetor hepaticus, literally “liver breath,” because of an accumulation of volatile waste products such as ammonia Figure 16-4 Three types of jaundice A, Prehepatic jaundice causes increased levels of unconjugated bilirubin in blood B, Hepatic jaundice may be caused by interference with the liver’s ability to conjugate bilirubin or to secrete it after conjugation; increased levels of blood bilirubin may be of either conjugated or unconjugated type C, Posthepatic jaundice is caused by obstruction of bile flow inside or outside of the liver; increased levels of blood bilirubin are of conjugated type 90981 ch 16.qxd 10/9/06 10:14 AM Page 397 Chapter 16 • Diseases of the Liver and Biliary Tract • Hypoalbuminemia because of diminished hepatic production of protein • Hypoglycemia because of lack of liver glycogen stores • Hyperammonemia because of failure of the liver to convert ammonia to urea • Palmar erythema (redness of the palms of the hands), spider angiomata (small skin hemangiomas), testicular atrophy, balding, and gynecomastia (enlarged male breasts) because of increases in blood estrogen from impaired liver metabolism of estrogen • Bleeding disorders because of deficiency of blood clotting factors made by the liver Moreover, kidney and brain function can be seriously impaired by liver failure (A summary of the clinical features of hepatic failure can also be found later in the chapter in Figure 16-10, which appears with the discussion of cirrhosis.) Hepatorenal syndrome is renal failure owing to acute hepatic failure The cause is not completely clear—it appears to result from renal vasoconstriction and low renal blood flow, but the kidney is pathologically normal Hepatic encephalopathy, an especially serious complication of hepatic failure, occurs when accumulated ammonia and other unmetabolized waste products exert a toxic effect on the brain Neurologic signs include rigidity, hyperreflexia, and, rarely, seizures Fatal coma may occur A particularly characteristic sign is asterixis, a rapid extension-flexion motion of the head and extremities that can be demonstrated by testing for “hepatic flap”—the arms are held extended and the hands dorsiflexed A pulsating, flapping, or hand waving motion constitutes a positive test 397 A B Figure 16-5 Cirrhosis A, Normal liver B, Cirrhosis Note the small size of the cirrhotic liver A Cirrhosis Cirrhosis is the final, common end-stage for a variety of chronic liver diseases As is illustrated in Figures 16-5 and 16-6, cirrhosis is a patterned fibrosis of the entire liver characterized pathologically by a three-dimensional web of interconnecting bands of scar tissue, dividing the liver into small nodules separated from one another by dense fibrous tissue, an architecture that makes cirrhotic livers tense and hard Cirrhosis is progressive, irreversible, and incurable Cirrhosis can be classified by cause, such as alcoholic or hepatitic, but regardless of cause there are only two anatomic types of cirrhosis: • portal cirrhosis, caused by diffuse liver cell injury • biliary cirrhosis, caused by chronic disease of the biliary tree B Nodule of hepatocytes Fibrous tissue Figure 16-6 Cirrhosis A, Gross section B, Microscopic study Note the nodular pattern in both specimens The liver is divided into nodules by a web of fibrous (scar) tissue Dark discoloration of some nodules is caused by the accumulation of bile pigment in lobules The cause of cirrhosis in this patient is unknown 90981 ch 16.qxd 398 10/9/06 10:14 AM Page 398 Part • Diseases of Organ Systems In early cases, portal and biliary cirrhosis are easy to distinguish by microscopic examination, but as disease progresses the distinctions disappear In the end the cause of most cases of cirrhosis cannot be determined by study of the liver: clinical findings and history are of paramount importance However, a few rare types of cirrhosis have highly characteristic microscopic findings For example, in hemochromatosis (discussed below), the body is overloaded with iron, much of which is deposited in the liver A second example is hereditary alpha-1 antitrypsin deficiency, which is associated with early emphysema (Chapter 14) and distinctive microscopic findings in the liver Table 16-2 lists the causes of cirrhosis and the microscopic pattern associated with each Cirrhosis is among the top 10 causes of death in the western hemisphere, two thirds of it resulting from alcoholism and chronic viral hepatitis Less common causes are genetic hemochromatosis, and diseases of bile ducts In about one third of cases, the cause is unknown (cryptogenic cirrhosis) ANATOMIC TYPES OF CIRRHOSIS The term portal cirrhosis is assigned to cirrhosis occurring with repeated episodes of liver cell necrosis that are followed by hepatocyte regeneration and growth of fibrous tissue from the area of the portal triad Portal cirrhosis is by far the most common type of cirrhosis Causes and Microscopic Types of Table 16-2 Cirrhosis Cause Microscopic Type Alcohol abuse Portal Chronic viral hepatitis B or C Portal Biliary obstruction Gallstones Cystic fibrosis Biliary Autoimmune disease Primary biliary cirrhosis Sclerosing cholangitis Autoimmune hepatitis Biliary Biliary Portal Inherited metabolic disease Hemochromatosis Alpha-1 antitrypsin deficiency Wilson disease Portal Cryptogenic (unknown) Portal and includes all forms of cirrhosis other than those described immediately below as biliary cirrhosis The majority of portal cirrhosis results from alcoholic liver disease and chronic viral hepatitis Far less common is biliary cirrhosis, which results from chronic inflammation of bile ducts Primary biliary cirrhosis is an autoimmune disease (Chapter 8) of intrahepatic bile ducts Secondary biliary cirrhosis develops as a consequence of prolonged inflammation of bile ducts, usually associated with obstruction of bile flow because of gallstones lodged in the common bile duct Another cause of bile duct inflammation and fibrosis that causes biliary cirrhosis is sclerosing cholangitis, which is associated with chronic ulcerative colitis (Chapter 15) THE PATHOPHYSIOLOGY OF CIRRHOSIS Cirrhosis obstructs free flow of portal blood through the liver and causes portal hypertension; that is, high blood pressure in the portal venous system This obstruction of portal blood flow through the liver diverts (shunts) blood around the liver through alternative (collateral) vessels in the GI tract, spleen, and skin, as is depicted in Figure 16-7 The hemodynamic consequences of portal hypertension are ascites, congestive splenomegaly (Fig 16-8), and various types of prominent veins that result from the shunting of blood around the liver: esophageal varices (see Fig 15-8, Chapter 15), hemorrhoids, and prominent veins radiating outward from the umbilicus, known as caput medusa—literally snake-head—so named because of its likeness to the female serpenthaired monster, Medusa, from Greek mythology Ascites (from Greek, askos, for bag) is an intraperitoneal accumulation of watery (serous) fluid This fluid seeps from portal venules as a result of high portal blood pressure and low blood osmotic pressure caused by low blood albumin owing to low output of albumin by the liver Ascites becomes clinically evident when about 500 ml of intraperitoneal fluid have accumulated; however, as is depicted in Figure 16-9, fluid accumulation may be massive Cirrhosis is always associated with portal hypertension CLINICAL FEATURES OF CIRRHOSIS The clinical features of cirrhosis are summarized in Figure 16-10 and result from four phenomena: • Failure to metabolize estrogen and ammonia Failing hepatic metabolism of estrogen results in high levels 90981 Index 10/12/06 10:19 AM Page 725 Index Page numbers in italics indicate figures Page numbers followed by “t” indicate tables Words in bold indicate diseases or conditions A Abdominal aortic aneurysm, 285 Abdominal obesity, 225 Abortion, 565 Abrasion, 207 Abscess, 44, 313 Absolute risk, relative risk, distinguished, 571 Absorption, 355 Abuse, 217, 366 Accumulated secretions, 340 Accumulation of neutrophils, 42 Acetaminophen, 215 Acetylcholine, 622 Achalasia, 358, 365 Acidosis, 300, 436 Acids, 25 Acne, 177, 663 Acne rosacea, 663 Acne vulgaris, 663 Acoustic neuroma, 642 Acquired immunodeficiency syndrome, 168, 173 infections, 194 pathologic features of, 171 phases of, 170 Acromegaly, 456, 456–457 ACTH adenoma, 457 Actin, 603 Actinic keratoses, 667, 667 Addiction, 217 Addison disease, 473, 474 bronze skin pigmentation, 475 Aden, 88–89 Adenocarcinoma, 89, 348, 366 Adenohypophysis, 450 Adenoma, 88, 455, 670 Adenomatous polyp, 380 Adenomyosis, 556, 557 ADH See Antidiuretic hormone Adhesions, 379 Adrenal cortex, 284, 454 Adrenal gland, 454 Adrenal hyperplasia, 471, 471 Adrenal medulla, 454 chromaffin cells, 454 Adrenergic effect, 620 Adrenocortical adenoma, 469, 469 Adrenocortical atrophy, 469 Adrenocortical hyperplasia, 468 Adrenocortical insufficiency, 472 Adrenogenital syndrome, 471, 471, 472 Adult polycystic disease, 493 Adult respiratory distress syndrome, 338, 338 Adventitia, 272 Afferent arteriole, 480, 483 African trypanosomiasis, 197 Age-related macular degeneration, 692 Agglutinins, 152–152t Agranulocytosis, 249 Agriculture chemicals, 212 Agyria, 624 AIDS See Acquired immunodeficiency syndrome Air pollution, 210 Airflow, 328 Airway hyperreactivity, 332 Aktin, 667 Albinism, 657 Alcohol abuse, 398, 409, 427, 429 cerebellar atrophy, 219 cirrhosis, 410 effects of, 218 fatty liver of, 219 hepatitis, 410 hypoglycemia, 442 liver, 410 Mallory’s alcoholic hyaline, 409 Aldosterone, 274, 454 Alkaline phosphatase, 585 Alkalis, 25 Alleles, 119 Allergens, 153, 159 Allergic alveolitis, 336 Allergic conjunctivitis, 159 Allergic contact dermatitis, 661 eczema, 662 Allergic rhinitis, 330 Allergy, 153, 159 Alopecia, 654 Alopecia areata, 654, 654 Alopecia totalis, 654 Alopecia universalis, 654 Alpha-1 antitrypsin, 123, 333, 412 Alpha-1 antitrypsin deficiency, 123, 412 Alpha-fetoprotein, 106 Alveolar pneumonia, 339, 339 Alveoli, 325 Alzheimer disease, 637, 638 Amblyopia, 682 Amebiasis, 197, 198 Amebic dysentery, 181, 374 Amenorrhea, 456, 555 Amino acids, 357 Aminoaciduria, 485 Amniocentesis, 130 Amniotic fluid, 79, 80, 83 Amphetamines, 220 Ampulla of Vater, 358, 392, 423 Amyloid, 167 Amyloidosis, 167, 167 Amyotrophic lateral sclerosis, 638, 638 ANA See Antinuclear antibodies Anaerobic infection, 47, 177, 191, 359 Anagen phase, 652 Anal fissures, 378 Analgesic nephropathy, 503 Anaphylaxis, 154, 159 Anaplastic carcinoma, 465 Anasarca, 72 Anatomic pathology, defined, Androgenic steroids, 454 Anemia, 240, 242–243, 244, 246–247, 490 Anencephaly, 113–114, 624, 624 Aneurysm, 277, 280, 629 Aneurysmal bone cyst, 594 Angina, 281, 304 Angina pectoris, 229 Angiodysplasia, 370 Angioedema, 661 Angioma, 669, 669 Angioneogenesis, 40, 44, 57, 58, 97, 439 Angiosarcoma, 287, 572 Angiotensin, 274 Angiotensin-converting enzyme, 274 Ankylosing spondylitis, 164, 599, 599 Annular pancreas, 427 Anorexia nervosa, 221 Anti-CCP See Anticyclic citrullinated peptide Anti-HAV antibodies, 403 Anti-phospholipid antibody, 266 Antibiotic sensitivity testing, 200 Antibiotics, discovery of, 184 Antibody, 149, 404, 565 Anticyclic citrullinated peptide, 599 Antidiuretic hormone, 459 Antigen-anti-HBs, 404 Antigen-antibody complex, 152 Antigen exposure, antibody response to, 151 Antigens, 148, 404 Antimicrobial protective mechanisms, 147 Antimicrobial susceptibility, 200 Antimitochondrial antibody, 413 Antinuclear antibodies, 161 Antireagin antibodies, 529–530 Antitreponemal antibody, 529 Aorta misplaced, 317 normal, 280 Aortic aneurysm, thrombus, 280 Aortic insufficiency, 310 Aortic stenosis, 310 Aortic valve disease, 294 725 90981 Index 726 10/12/06 10:19 AM Page 726 Index Apgar score, 134 Aphthous ulcers, 363 Aplastic anemia, 247, 247 Apnea, 283 Apoplexy, 627 Apoproteins, 275 Apoptosis, 24, 29 Appendicitis, 384, 384 Aqueous humor, 679 Arachnoid granulations, 614 Arbovirus encephalitis, 637 Arcus senilis, 685, 686 Arrhythmia, 297 Arteries, 271 Arteriole, 274 Arteriolosclerosis, 277 Arteritis, 286 Arthritis, 162, 310 joint changes in, 597 rheumatoid, 598 Articular cartilage, 595 Asbestos, 210 Asbestosis, 336 Ascariasis, 196 Ascaris species, 196 Ascending cholangitis, 413, 417 Ascites, 72, 396, 398, 400 Aseptic meningitis, 634 Aseptic necrosis, 589 Askos, 398 Aspergillus species, 92, 181 Aspiration pneumonia, 341 Aspirin, 214 Asterixis, 397 Asthma, 331, 332, 349–350 Asthmatic bronchitis, 332, 334 Astigmatism, 684 Astler-Coller staging, 382–382t, 383 Astrocytes, 622 Astrocytoma, 641, 642 Asymptomatic hepatitis, 402 Atelectasis, 330, 331 Atheroma, 277, 278 Atherosclerosis, 277, 281, 298, 303 Atherosclerotic debris, 79 Athletes’ foot, 518 Atom, defined, 15 Atopic dermatitis, 159, 662 Atopy, 159, 332 Atresia, 370 Atrial fibrillation, 298, 300 Atrial flutter, 298 Atrial septal defect, 316 Atrioventricular node, 295 Atrophic gastritis, 247, 368 Atrophy, 28 Auditory nerve, 697 Auricle, 696 Autoimmune antibodies, 162 Autoimmune destruction, 434 Autoimmune disease, 160t Autoimmune hepatitis, 407 Autoimmune reaction, 159 Autoimmune vasculitis, 243 Autoimmunity, 149, 153–154, 159, 309, 494, 655 Autonomic nervous system, 613, 619, 621 Autopsy, Autosomal dominant, 119 Autosomal recessive, 119 Autosomes, 116 Avascular necrosis, 589 Avulsion, 601 Axons, 603, 620 Azoospermia, 517 Azotemia, 487, 490 B B cells, 148–149 See also B lymphocytes B lymphocytes, 45 Bacillary dysentery, 372 Back pain, 601 Bacteria, 47, 177, 181t, 187, 520 See also under specific bacteria Bacterial culture, 200 Bacterial cystitis, 515 Bacterial endocarditis, 312–313, 313 Bacterial enterocolitis, 372, 373 Bacterial pneumonia, 340 Bacterial prostatitis, 520 Balanitis, 517 Balding, 397 Band keratopathy, 686, 686 Band neutrophil, 251 Barbiturates, 220 Barrett esophagus, 366 See also Barrett metaplasia Barrett metaplasia, 31, 358, 366 Barrier effect, 484 Bartholin abscess, 545 Bartholin glands, 538 Bartonella henselae, 252 Basal cell carcinoma, 668, 668, 697 Basal cells, 649 Basal ganglia, 637–638 Basement membrane, 16, 55, 55, 272, 649 Basophils, 36, 38, 236 Becker muscular dystrophy, 606 Bell’s palsy, 643 Bence Jones protein, 253 Bends See Decompression sickness Benign nephrosclerosis, 284, 498, 498–499 Benign tumors, characteristics of, 93t Benzodiazepines, 220 Beriberi, 222 Berry aneurysm, 629 Bicuspid aortic valve, 310 Bile, 392 Bile acids, 394 Bile duct, 391, 392 Biliary atresia, 412, 417 Biliary cirrhosis, 397–398, 413, 413 Biliary obstruction, 395 Biliary tract, 389–421 Bilirubin, 392 Bilirubinuria, 488 Biologic false positives, 530 Biopsy specimen, defined, Birth defects, preventing, 114 Blackheads, 663 Bladder, 480 Bleb, 333 Bleeding/coagulation defects, 490 Bleeding disorders, 260–284, 397 See also under specific disorder lab tests, 262 Bleeding time, 263 Blefaros, 684 Blepharitis, 684 Blindness, 691 Blood, composition of, 237 Blood amylase, laboratory tests for, 430 Blood BUN, 486 Blood cells diseases, 235–260 normal reference ranges, 236t Blood circulation, 272, 316, 392 Blood coagulation, 234–269 Blood corpuscles, 39 Blood flow, disorders of, 65–85 Blood glucose testing, 12 Blood lipid abnormalities, 655 Blood pressure, 66, 282–283t functions, 67 measuring, 282 regulation of, 274 Blood transfusion, 165 Blood typing, 165 Blood urea nitrogen, 485 Blood vessels, 270–292 anatomy of, 273 BMI See Body mass index Body mass index, 224–225t Bone, diseases of, 582–594 Bone anatomy, 584 Bone infarcts, 589 Bone marrow malignancies, 250 Bone tumors, primary, common sites of, 592 Bony callus, 587 Borderline malignant, 561 Borrelia species, 137, 182, 187, 195, 600 Botulism, 193 Bowel obstruction, 362 Bowen disease, 518, 518 Bowman space, 481, 484 Brachial plexus, 619 Brain, 135, 162, 616 arterial blood supply to, 619 functional anatomy of, 617 lymphoma, 642 Brain abscess, 636, 636 Brain edema, 626 Brain herniations, 625 Breast, 303 anatomy, 569 diseases of, 568–581 fibrocystic change, 570 phyllodes tumor, 572 Breathing, rapid, deep, 436 Brittle bone disease, 585 Broad ligament, 538 Broad-spectrum antibiotic therapy, 372 Bronchial dysplasia, 136 Bronchial epithelium, 340 Bronchiectasis, 335 Bronchiole, 325 Bronchiolitis, 137 Bronchitis, 333–334 emphysema, relationship, 334 Bronchogenic carcinoma, 347 types of, 347 Bronchopneumonia, 201, 339 Bronchus, 325 Brush border, 358 90981 Index 10/12/06 10:19 AM Page 727 Index Bruton disease, 167 Budd-Chiari syndrome, 414 Bulimia, 221 Bulla, 333 Bullous pemphigoid, 659 Bundle of HIS, 296 Bunion deformity, 596 Burns, 209 Bursitis, 601 C C-reactive protein, 46, 280 Cachexia, 101 of malignancy, 99 Calcific aortic stenosis, 310, 312 Calcitonin, 465 Calcium stone, renal pelvis, 504 Calculi, 503 Calymmatobacterium granulomatis, 532 Campylobacter species, 164, 189, 372, 599 Canal of Schlemm, 693 Cancellous bone, 583 Cancer See also under specific type causes of, 91 genetic inheritance, 100t treatments, 104t Cancer of bladder, 516 Cancer of breast, 105, 572t, 573, 575, 578 Cancer of cervix, 105, 532, 545, 550, 552, 555, 576 Cancer of colon, 105, 266, 381, 382, 384–385 Astler-Coller staging system, 383 clinical stages, 382t Cancer of esophagus, 366 Cancer of larynx, 330 Cancer of lung, 105–106 smoking, relationship, 217 Cancer of pancreas, 431, 432 Cancer of prostate, 105, 524 Cancer of skin, 652 Cancer of testis, 520 Cancer of thyroid, 465 Cancer of uterus, 557 Candida species, 168, 181, 193, 345–346, 363–364, 545, 568, 654 Candidiasis, 193, 346, 364, 545 Capillaries, 39 Capillary hemangioma, 287, 669 Caput medusa, 398 Carbohydrates, 357 Carbon monoxide poisoning, 210, 210 Carbon particles, 27 Carbon pigment, intracellular accumulation of, 27 Carcinoembryonic antigen, 106, 382, 576 Carcinogenesis, 91 Carcinogenic, 118 Carcinoma, 88, 571–572t Carcinoma in situ, 94, 94, 572 Carcinoma of bladder, 516 Carcinoma of breast, 105, 573, 575, 578 Carcinoma of cervix, 105, 532, 545, 550, 552, 555, 576 Carcinoma of colon, 105, 266, 381, 382, 384–385 Astler-Coller staging system, 383 clinical stages, 382t Carcinoma of esophagus, 366 Carcinoma of kidney Carcinoma of larynx, 330 Carcinoma of liver Carcinoma of lung, 105–106 smoking, relationship, 217 Carcinoma of ovary Carcinoma of pancreas, 431, 432 Carcinoma of prostate, 105, 524 Carcinoma of skin, 652 Carcinoma of stomach, 359 Carcinoma of testis, 520 Carcinoma of thyroid, 465 Carcinoma of uterus, 557 Cardiac chambers, valves, 295 Cardiac output, 273 Cardiac shunt, 315 Cardiac troponin, 307 Cardiac valves, 294 Cardiogenic shock, 81 Cardiomyopathy, 314–315 dilated, 314 Caries, 361 Carotid artery, 631 Carpel tunnel syndrome, 602 Carrier state, 402, 407 Carriers, 184, 242 Caseous necrosis, 30, 341 Cat scratch fever, 252 Catagen phase, 652 Cataract, 439, 686, 687 surgery for, 687 Catecholamines, 274, 454 Cavernous hemangioma, 287, 414 CBC See Complete blood count CEA See Carcinoembryonic antigen Celiac sprue, 374, 659 Cell death, 24 Cell repair, 51–64 Cellular hypersensitivity, 158 Cellular immunity, 45, 158 Central nervous system, 613, 614 Cerebellar tonsillar herniation, pontine hemorrhage secondary, 626 Cerebellum, 613 Cerebral cortex, 637 vascular malformation, 630 Cerebral hemispheres, 613 Cerebral palsy, 136, 624, 624 Cerebrospinal fluid, 614, 615 laboratory examination of, 635 Cerebrovascular accident, 627 Cerebrum, 613, 632 Ceruloplasmin, 412 Cervical cancer, 532 Cervical epithelium, changes with age, 547 Cervical erosion, 548 Cervical intraepithelial neoplasia, 549 Cervical plexus, 619 Cervicitis, 548–549 Cervix, 538, 550t, 552t ectropion, 548 Pap smear, 102, 102, 549, 551, 552–553, 554 squamocolumnar junction, 548 Cestodes, 196 Chagas disease, 197 Chalazion, 684 Chancre, 189, 527, 527 727 Chancroid, 532, 544 Charcot-Bouchard microaneurysms, 630 Charcot joint, 440 Chemical, 92, 275 Chemokines, 41 Chemotaxis, 41 Chest cold, 106–107 Chest pain, 229 Chickenpox, 137 Chimney sweeps’ cancer, 211 Chlamydia, 181, 189–190, 195, 200, 340, 515–516, 530–532, 545, 560, 568, 599, 684 Cholangiocarcinoma, 415, 417 Cholangitis, 416, 416, 417, 417 Cholecystitis Cholelithiasis, 415, 416–417 Cholera, 189, 372 Cholestasis, 396 Cholesteatoma, 699 Cholesterol, 275–276, 279, 357 Cholesterol gallstones, 415, 416 Cholinergics, 620 Cholinesterase, 603, 622 Chondrosarcoma, 593, 593 Choriocarcinoma, 520, 566–567 Chorionic gonadotropin, 542 Choristoma, 139 Choroid, 682, 687 Choroiditis, 687 Christmas disease, 264 Chromosome, 17 subdivisions of, 19 Chronic disease, defined, Chronic non-specific lymphadenitis, 252 Chronic nonbacterial prostatitis, 520 Chronic obstructive pulmonary disease, 332, 349 Cigarette asthma, 349–350 Cigarette smoking, 279, 333, 349 effects of, 201, 216 lung cancer, relationship, 217 Cilia, 20 Ciliary body, 679 Ciliary muscle, 679 Circulating antigen-antibody complexes, 494 Circulation of blood, 272, 316, 392 Circumcision, 511 Cirrhosis, 365, 394, 397, 397, 398–398t, 399–400, 413 CJD See Creutzfeldt-Jacob Disease CK-MB, 307 Classic hemophilia, 124 Clear cell carcinoma, 505 Cleft lip, 361 Cleft palate, 361 Clinical pathology, defined, Clitoris, 537 Clone, 96, 252 Closed-angle glaucoma, 693 Closed fracture, 586 Clostridium, 193 Clostridium botulinum, 186 Clostridium difficile, 193, 372 Clostridium perfringens, 47, 193, 607 Clostridium tetani, 193, 607 Clotting system, 40, 76 CMV See Cytomegalovirus 90981 Index 728 10/12/06 10:19 AM Page 728 Index Coagulation, 30, 75, 78, 260 Coagulation factors, 262 Coagulative necrosis, 30, 30 Coarctation of aorta, 318 Cocaine, 220 Coccidioides species, 188, 346 Coccidioidomycosis, 188, 346 Cochlea, 697 Cold sore, 191, 363, 664, 665 Collecting systems, 480, 510 Colloid, 452, 463 Colon, 380, 381 Colon cancer, 381 Colonic adenoma, 380 dysplastic change in, 381 Colonic adenomas, 380 Comedo, 663 Comminuted fracture, 586 Common bile duct, 392, 423 Common colds, 187 Community-acquired pneumonia, 340 Compensated heart failure, 299 Complement system, 40, 154 Complete blood count, 237 Complete fracture, 586 Complete resolution, 44 Complex hyperplasia, 557 Components of blood, 38t Compression atelectasis, 331, 331 Compression fracture, 586 Concussion, 633 Conductive hearing loss, 699 Condyloma acuminatum, 189, 531, 544, 546, 666 Condyloma lata, 528, 528, 531, 545–546 Cones, 680 Confabulation, 218 Congenital abnormalities, 111, 114–115, 139, 310, 370, 377, 471, 471, 502, 517, 529 Congestive heart failure, 74, 298, 301, 314 Congestive splenomegaly, cirrhosis, 399 Conjugated bilirubin, 392, 396 Conjunctiva, 678, 685 Conjunctivitis, 365, 684 Conn syndrome, 470 Consumptive coagulopathy, 76, 265 Contact dermatitis, 661 Contagion, 184 Contraction atelectasis, 331 Contrecoup injury, 633, 634 Convalescence, 197, 402 Coombs tests, 165–166 COPD See Chronic obstructive pulmonary disease Cor pulmonale, 300, 335, 338 Cornea, 678–679, 682 Corneal dystrophy, 686, 686 Corneal ulcer, 685 Coronary artery atherosclerosis, 298 thrombosis, 304 Coronary occlusion, 281 Coronary sinus, 295 Coronary thrombosis, 304 Coronary vasospasm, 304 Coronary veins, 295 Corpus albicans, 542 Corpus cavernosum, 510 Corpus luteum, 542 Corpus spongiosum, 510 Cortex, 454, 468, 614 Cortical hormones, 474 Cortisol, 454 Corynebacterium diphtheriae, 137, 187 Councilman bodies, 394, 409 Coup-contrecoup injury, 633, 634 Coxsackie A or B, 314 Cradle cap, 658 Cranial nerves, 618 Craniopharyngioma, 455 Creatine kinase, 307, 606 Creatinine, 485–486 Crepitus, 596 Crescentic glomerulonephritis, 496 Cretinism, 463 Creutzfeldt-Jakob disease, 181, 637 Crohn disease, 374, 375, 375t, 376 Croup, 137 Cryptococcosis species, 193, 346, 634 Cryptorchidism, 518, 518 Cryptosporidiosis, 197 Cryptosporidium parvum, 193 CSF See Cerebrospinal fluid Cushing syndrome, 458, 468, 470–471 laboratory diagnosis of, 472 pathogenesis of, 469 Cutaneous lupus erythematosus, 660 Cyanosis, 316 Cystadenocarcinoma, 561 Cystic disease, 493, 561 Cystic fibrosis, 124, 431 laboratory testing for, 139 lungs in, 139 Cystic hyperplasia, 557 Cystic medial degeneration, 285 Cystic serous tumor, ovary, 563 Cysticercosis, 197 Cystitis, 515, 515 Cystocele, 515, 560 Cytogenetic disease, 26, 117, 125, 129 Cytokines, 41, 149 Cytomegalic inclusion disease, 193 Cytomegalovirus, 170, 193, 346 Cytoplasmic organelles, 19 Cytotoxic edema, 626 Cytotoxic hypersensitivity, 156 Cytotoxic T cells, 149, 152, 158 Cytoxicity, 159 D Dacryocystitis, 685 Dandruff, 658 Darkfield microscopy, 527 De Quervain thyroiditis, 464 Deafness, 677–703, 696, 696–703, 698 Decompression sickness, 79 Decreased cough reflex, 340 Deep mycoses, 346 Defective liver processing, 395 Deformations, 111 Degenerative disc disease, 601 Degenerative joint disease, 595 Degranulation, 37 Dehiscence, 61 Dehydration, 71, 371 Delayed hypersensitivity, 158 Delayed immunity, 152 Dementia, 637 Dendrites, 620 Denervation, 605 Deoxyribonucleic acid See DNA Depressants, 220 Dermatitis, 658, 662 Dermatitis herpetiformis, 659 Dermatofibroma, 669, 669 Dermatomyositis, 607 Dermatophytes, 191, 665 Dermatophytosis, 664 Dermis, 651, 665 Dermoid cyst, 564 Desmoid tumors, 608 Detectable, defined, Developmental abnormalities, 111–115 Diabetes, 164, 277, 279, 433–434, 434–435, 654 derivation of word, 434 laboratory diagnosis, 441 long-term complications of, 438 type 1, type 2, compared, 433 Diabetes insipidus, 459 Diabetes mellitus, 12, 433 Diabetic coma, 436, 437 Diabetic glomerulosclerosis, 498 Diabetic nephropathy, 439 Diabetic nephrosclerosis, 439, 439 Diabetic nodular glomerulosclerosis, 439 Diabetic peripheral neuropathy, 605, 643 Diabetic retinopathy, 439, 440, 691 Diabetic ulcer, 656 Diagnosis defined, 11 tests in, usefulness of, 10–12 Dialysis, 486 Diaphysis, 583 Diarrhea, 188, 371 Diastole, 271, 297 Diet, 205–232 Dietary sodium, 283 Differentiated teratoma, 519 Diffuse axonal injury, 633 Diffuse lymphoma, 256 Diffusion capacity, 328 DiGeorge syndrome, 168 Digestive system, 355, 356–357 Dilated capillaries, 42 Dilated cardiomyopathy, 308, 314, 314 Dilutional anemia, 240 Dimorphic fungi, 346 Dioxin, 212 Diphtheria, 137 Diplopia, 17, 682 Direct contact, 184 Discoid lupus erythematosus, 660 Disease defined, Dislocation, 601 Dissecting hematoma, 285 Disseminated intravascular coagulation, 76, 243 Disuse atrophy, 605 Diverticulitis of colon, 377, 379 Diverticulosis of colon, 377, 379 Diverticulum, 377 90981 Index 10/12/06 10:19 AM Page 729 Index DNA, 17, 22, 118 repair system, 91 Dominant genes, 119 Donor plasma, 165 Donor RBCs, 165 Dopamine, 638 Down syndrome, 127, 128 chromosomes in, 126 Droplets, 184 Drug abuse, 220 Dubin-Johnson syndrome, 396 Duchenne muscular dystrophy, 606 Ductal carcinoma, 572–573 Ducts, 423 Duodenum, 358, 368 Dura mater, 614 Dust cells, 328 Dyscrasia, 252 Dysentery, 189, 371 Dysfunctional uterine bleeding, 555 Dysmenorrhea, 555 Dysphagia, 330, 358, 365 Dysplasia, 29, 31, 94–95, 545, 549, 550–551 Dysplastic nevus, 671 Dystrophic calcification, 31 E Ear, 677–703, 698 anatomy of, 696 diseases of, 696–703, 698 Ear lobe, keloid, 61 Early diabetic retinopathy, 691 EBV, 170, 251 Ecchymosis, 75, 76 Echinococcosis, 197 Eclampsia, 568 Ectocervix, 538 Ectoderm, 15 Ectoparasites, 182 Ectopic pancreas, 427 Ectopic pregnancy, 560, 565 fallopian tube, 566 Ectropion, 548 Eczema, 662, 662 Edema, 72, 490 Efferent arteriole, 480, 483 Effusions, 72, 300 Eggs, 197 Ejection fraction, 299 Electrical activity of heart, 296 Electrocardiogram, 297 Embolus, 78–79 Embryo development, critical stages of, 112 Embryonal carcinoma, 519–520 Emergency salt water therapy, 72 Emphysema, 333 bronchitis, relationship, 334 microscopic development, 334 Empyema, 416 cholecystitis with, 416 Enchondroma, 593 End-stage renal disease, 492, 498 Endocardium, 294 Endocervical canal, 538 Endocervical polyp, 548, 548 Endochondral ossification, 583 Endocrine system, 423–424, 448–478, 450 Endoderm, 16 Endometrial adenocarcinoma, 557 Endometrial carcinoma, 559 Endometrial cycle, 542 Endometrial hyperplasia, 556, 558 Endometriosis, 555, 556–557, 560 Endometrium, 538 Endometrioid tumors, 561 Endomyocardial fibrosis, 315 Endoplasmic reticulum, 20 Endosteum, 583 Endothelial cell, 39, 69, 272, 278, 484 Endothelium, 272 Endotoxins, 81, 186 Entamoeba histolytica, 197, 374, 408 Enteritis, 188 Enterobius vermicularis, 196 Enterococcus, 313 Enterocolitis, 372 Enterohepatic circulation, 282, 392, 393, 394 Entropion, 684 Enzymes, 122, 423, 622 Eosinophilia, 36, 38, 47, 196, 236, 251 Ependymal cells, 622 Ependymomas, 641–642 Epicardium, 293 Epidemic typhus, 195 Epidemics, 184, 402 Epidemiology, 100 Epidermal growth factor, 56 Epidermis, 648–673 neoplasms of, 665–677 normal, 650–651 pigmentation, 657 Epidermoid cyst, 665, 666 Epidermolysis bullosa, 659 Epididymis, 511 Epididymitis, 519 Epidural, 627 Epidural hematoma, 627, 628 Epiglottitis, 137 Epinephrine, 454 Epiphyseal growth plate, 583 Epispadias, 517 Epithelial cells, 484, 561 Epithelial hyperplasia, 570 Epithelial malignancy, 94 Epithelium, 16, 556 Epstein-Barr virus, 136–137, 170, 251 Equilibrium, 372 Erectile dysfunction, 517 Erection, 510 Erosions, 367 Eruptive xanthomas, 655 Erysipelas, 191, 664, 664 Erythema migrans, 600 Erythema multiforme, 660 Erythema nodosum, 663 Erythrocyte sedimentation rate, 46, 48 Erythrocytes, 236 Erythrocytosis, 248 Erythropoietin, 236, 248, 480, 483 Escherichia coli, 183, 185, 191, 193, 340–341, 372, 502, 515, 520, 634 Esophageal hiatus, 358 Esophageal varices, 287, 365, 366, 398 ESR See Erythrocyte sedimentation rate Essential hypertension, 283 Essential thrombocythemia, 259 729 Esterase, 487 Estrogen replacement therapy, 543 Ethanol, 217, 220 Etiology, defined, Eunuch, 523 Euploid, 17 Eustachian tube, 697 Euthyroid, 452 Ewing sarcoma of bone, 594 Excess granulation tissue, 61 Exchange transfusion, 135 Excitatory-conduction system, 295 Excretory failure, 400 Exocrine, 423 Exocytosis, 20 Exophthalmos, 459, 684 Expansion defects, 315 Experimental evidence, 348 Exstrophy, 514 External auditory canal, 696 External ear, 696 External hemorrhoids, 371 External hydrocephalus, 626 External respiration, 325 External urethral orifice, 537 Extracellular matrix, 55–56 Extrahepatic biliary obstruction, 418 Extramedullary hematopoiesis, 258 Extraparenchymal, 627 Extravascularly, 76 Extrinsic coagulation pathway, 262 Exudate, 72, 349 Eye anterior segment of, 681 diseases of, 678–695 glaucoma, 694 Eyelid, 678, 685 F Facial nerve, 697 Facies, Down syndrome, 128 Factor V Leiden, 266, 337 Fallopian tube, 538, 539, 566 False negative, False positive, Falx cerebri, 614 Familial hypercholesterolemia, 124 Familial polyposis, 381 Farmer’s lung, 158 Fat necrosis, 31, 569 Fat solubility, 221 Fatigue, 266–267 Fatty heart syndrome, 227 Fatty liver of alcoholism, 219, 409 Faulty meiosis, 129 Fecalith, 384 Female genitalia, 536–580, 538, 540, 544t Femur, osteoarthritis, 596 Ferritin, 27 Fetal alcohol syndrome, 114, 134, 219 Fetal blood circulation, 316 Fetor hepaticus, 396 Fever blister, 363 Fibrillation, ventricular, 298, 309 Fibrinogen, 46 Fibrinous inflammation, 43, 43 Fibroadenoma of breast, 571 Fibrocystic change of breast, 569–570, 570 90981 Index 730 10/12/06 10:19 AM Page 730 Index Fibrocyte migration, 57 Fibroepithelial polyp, 665 Fibroid tumor of uterus, 558 Fibromatosis, 608 Fibromyalgia, 602, 609 Fibrosarcoma, 89, 594, 608 Fibrosis, 44 Fibrous cortical defect of bone, 593 Fibrous dysplasia of bone, 593 Fibrous histiocytoma Fibrous joints, 594 Fibrous repair, 57, 57 Fibrous xanthoma, atypical, 608 Filariasis, 196 Filum, 196 Fimbriated extremity, 538 Fine needle aspiration, 103 Fixed macrophages, 392 Flat bones, 583 Flatworms, 196 Floaters, 689 Fluid balance, disorders of, 65–85 Fluid flow, microcirculation, 69 Foam cells, 279 Focal segmental glomerulosclerosis, 494 Folate, 246 Folic acid, 114, 246 Follicle, 540 Follicle cysts, 560 Follicle stimulating hormone, 458, 540 Follicles, 452 Follicular carcinoma, 465 Follicular lymphoma, 256 Food allergy, 159 Foot drop, 601 Foramen magnum, 618 Foramina of Luschka and Magendie, 614 Forced expiratory volume, 328 Forced vital capacity, 328 Fournier gangrene, 193 Fovea, 682 Fracture, 586 complete, 586 healing of, 588 types of, 587 Frank-Starling curve, 299 Frank-Starling Law, 299 Freckle, 657 Frostbite, 209 Frostnip, 209 Fructosamine, 439 FSH See Follicle stimulating hormone Fulminant hepatic failure, 402 Fulminant hepatitis, 402 Function, defined, Functional disorder, defined, Functioning adenoma, 455–456 Fundus, 358, 538 Fungi, 181, 188 Fusiform, 177, 285 G Gallstones, 415, 427 Gamma globulin, 151 Ganglia, 620, 622 Ganglion cyst, 602, 602 Ganglioneuroma, 643 Gas gangrene, 193, 607 Gastric stress ulcers, 368 Gastrin, 358 Gastrinomas, 442 Gastritis, 189, 367, 367 Gastroenteritis, 372, 490 Gastroesophageal junction, 358 Gastrointestinal bleeding, 359 Gastrointestinal infection, 188 Gastrointestinal tract, 354–388 Gastroschisis, 370 Gaucher disease, 122 Gene inheritance, 17, 111, 117, 120–121, 279 Genetic disease, 117t laboratory diagnosis in, 132 Genetic disorders, 116–132 Genetic enzyme deficiency, 395 –396 Genital herpes, 531 Genital ulcer, 527 Genitalia female, 536–580, 538, 540, 544t male, 509–535, 512 Genitourinary infections, 190 Genotypes, 116, 152 Germ cells, 116, 561 division of, 127 Gestational age, 133 Gestational diabetes, 436, 440 Ghon complex, 342 Ghon tubercle, 342 Giant cell arteritis, 286, 600–601 Giant cell tumor of tendon sheath, 602 Giardia species, 47, 181, 197, 372, 374 Giardiasis, 197, 374 Gigantism, 456 Gilbert syndrome, 395 Gingivitis, 363 Glaucoma, 439, 693, 694, 695, 700 surgery for, 687 Gleason score, 523 Glia, 622 Glioblastoma multiforme, 641, 642 Glioma, 641 Global hypoxia of brain, 632 Global ischemia, 632 Globe, 678–679 internal anatomy of, 680 Glomerular filtrate, 481, 483–484 rate, 484 tubular processing, 485 Glomeruli, 481 Glomerulonephritis, 162, 491, 494–495, 495, 497, 506 Glomerulus, 480, 492 anatomy of, 483 Glucagon, 424 metabolism of, 426 Glucose, 426 production of, 454 Glucose-6-phosphate dehydrogenase deficiency, 242 Glucose tolerance test, 440, 441 Glue ear, 699 Glutamic acid, 118 Gluten-sensitive enteropathy, 374 Glycogen metabolism, 426 Glycogen storage disease, 123 Glycohemoglobin, 439 Glycosuria, 436, 489 Glycosylation, 438 Goblet, 358 Goiter, 459, 463, 463 Golgi apparatus, 20 Gonadotropin-releasing hormone, 540 Gonococcus, 530 Gonorrhea, 189, 530, 531 Gout, 600 Graafian follicle, 540, 560 Graft-versus-host reaction, 165 Gram negative, 177 Gram positive, 177 Gram stain, 177, 180, 199, 531 Granular endoplasmic reticulum, 20 Granulation tissue, 58, 59 Granulocyte, 36, 236, 257 Granulocytosis, 251 Granuloma annulare, 661 Granuloma inguinale, 532, 544 Granulomas, 45, 159 Granulomatous enteritis, 374 Granulomatous inflammation, 45, 45, 335, 341, 344 Granulomatous thyroiditis, 464 Granulosa cells, 539 Granulosatheca cell tumor, 563 Graves disease, 459 Gray matter, 614, 620, 637 Greenstick fracture, 586 Gross examination, defined, Gross hematuria, 487 Growth factors, 56 Growth hormone, 456 Gunshot wound, 208 Gynecomastia, 397 H Haemophilus ducreyi, 532 Haemophilus influenzae, 137, 340, 634 Hallucinogen, 221 Hamartoma, 139, 347 Haploid, 17 Haptens, 149 Hashimoto thyroiditis, 464, 464 Haversian canals, 583 Hay fever, 159 Hazardous materials, 212t HbsAg, 404 HCV-RNA, 406 HDL cholesterol, 275 Healing by first intention, 60 Healing by second intention, 60 Health, defined, Heart anterior view, 294 electrical activity of, 296 Heart block, 298 Heart disease, 292–324 Heart failure, 74, 298, 301 compensated, 299 Heartburn, 31–32, 319–321 Heat cramps, 209 Heat exhaustion, 209 Heat stroke, 210 Heavy chain disease, 151, 253 Heberden nodes, 596 Helicobacter pylori, 47, 189, 367–369, 442 Helminths, 181, 195 90981 Index 10/12/06 10:19 AM Page 731 Index Helper T cells, 152, 160 Hemangioma, 139, 287, 669, 669 Hemarthrosis, 264 Hematemesis, 359, 367 Hematochezia, 359, 371 Hematocrit, 239 Hematologic diseases, 656 Hematomas, 75 subdural, 629 Hematopoiesis, 238 Hematoxylin, 37 Hematuria, 489 Hemochromatosis, 243, 398, 410–411, 411 complications of, 411 primary, 410 secondary, 411 Hemodynamic edema, 337 Hemodynamic pressure, 66 Hemoglobin, 237, 239, 241–242, 439 Hemoglobinopathies, 242 Hemoglobinuria, 489 Hemolysis, 237, 241, 243 Hemolytic anemia, 265 Hemolytic disease of newborn, 137 Hemopericardium, 319 Hemophilia, 124, 264 Hemoptysis, 330 Hemorrhage, 75, 247, 265 Hemorrhagic diathesis, 76, 263 Hemorrhagic gastritis, 367 Hemorrhagic pancreatitis, 427, 429, 429 Hemorrhoids, 287, 370, 371, 378, 398 Hemosiderin, 27 Hemostasis, 260, 261–262, 263 Hemothorax, 349 Hepatic duct, 392 Hepatic encephalopathy, 397, 639 Hepatic failure, 396 Hepatic lobule, 392 Hepatic malfunction, 395 Hepatic sinusoids, 392 Hepatitis, 394, 401–401t, 402, 403, 404, 404–405, 406, 406, 407, 407, 418–419 Hepatocellular carcinoma, 414, 414 Hepatocytes, 392 Hepatorenal syndrome, 397 Hereditary nonpolyposis colorectal carcinoma syndrome, 381 Hereditary polycystic kidney disease, 493 Hereditary spherocytosis, 242 Heritable melanoma syndrome, 671 Hernia, 370 Herniated intervertebral disc, 601, 601 Heroin, 221 Herpes virus infection of genitalia, 136, 190, 363, 531, 544, 699 Herpetiformis, 659 Heterophil antibodies, 137, 251 Heterosexual, 191 Heterozygous, 119 Hiatal hernia, 358, 365 High-grade tumors, 516, 641 Highly sensitive tests, defined, Highly specific tests, defined, Hirschsprung disease, 370 Hirsutism, 654 Histamine, 38, 41 Histoplasma capsulatum, 181, 188, 346 Histoplasmosis, 188, 346 HIV See Human immunodeficiency virus HLA See Human lymphocyte antigens HNPCC See Hereditary nonpolyposis colorectal carcinoma syndrome Hodgkin lymphoma, 255, 256 Homeostasis, 23, 449 Homocysteine, 279 Homoios, 23 Homozygous, 119 Hookworms, 196 Hordeolum, 684 Hormones, 23, 23, 424, 449–450, 523 Horseshoe kidney, 493 Hostile patient, 48 HPV See Human papillomavirus Human immunodeficiency virus, 168, 169, 191, 654 phases of, 170 T lymphocytes in, 169 Human lymphocyte antigens, 149 Human papillomavirus, 189, 518, 531, 544, 546, 549, 551 Humoral immune system, 45, 149 Hunner ulcers, 516 Hyaline arteriolosclerosis, 277, 284, 284, 439 Hydatid disease, 197 Hydatidiform mole, 197, 566, 567 Hydatis, 566 Hydrocele, 518 Hydrocephalus, 626, 626, 627 Hydrochloric acid, 358 Hydrocortisone, 454 Hydrolysis, 357 Hydronephrosis, 500, 502 Hydropericardium, 72 Hydropic change, 26 Hydrops fetalis, 138, 138 Hydrostatic edema, 67, 72 Hydrostatic pressure, 67 Hydrothorax, 72 Hyperacute organ rejection, 164 Hyperaldosteronism, 470–471 Hyperammonemia, 397 Hypercalcemia, 466, 468 Hypercholesterolemia, 124 Hyperchromatism, 93 Hyperemia, 74 Hyperglycemia, 433 Hyperkeratosis, 364 Hyperlipidemia, 492 Hypernephroma, 505 Hyperopia, 683 Hyperosmolar coma, 436 Hyperparathyroidism, 466, 466, 467, 467 Hyperplasia, 28, 29, 557 Hyperplastic arteriolitis, 284 Hyperplastic arteriolosclerosis, 277 Hyperplastic polyp, 380 Hypersensitivity disease, 153, 158, 336 Hypersplenism, 260 Hypertension, 277, 279, 282–283, 288, 398, 399, 400, 490 Hypertensive encephalopathy, 284 Hypertensive retinopathy, 284, 690 Hyperthyroidism, 452, 459, 460–461 Hypertrophic cardiomyopathy, 314 Hypertrophy, 28, 28 731 Hypoalbuminemia, 74, 397, 491 Hypogammaglobulinemia, 253 Hypoglycemia, 397, 442 Hypospadias, 517 Hypothalamus, 450, 451 Hypothermia, 209 Hypothyroidism, 452, 460, 461, 462, 475 Hypovolemic shock, 81 Hypoxia, 300 I Iatrogenic, defined, Iatros, defined, Icterus, 392, 395 Idiopathic, defined, Idiopathic dilated cardiomyopathy, 314 Idiopathic pulmonary fibrosis, 336 Ileitis, 374–375 Ileum, 358 Ileus, 361, 370 Immediate hypersensitivity, 155 Immune cell neoplasms, 670 Immune complex, 154 Immune-complex hypersensitivity, 157 Immune paint, 149, 328 Immune surveillance, 100 Immune system, 144–175, 148, 154, 155–157, 158, 158, 665 sequence of, 150 Immune thrombocytopenic purpura, 264 Immunodeficiency, 153, 167 Immunoglobulins, 45, 151, 168, 497 Impacted fracture, 586 Impaired fasting glucose, 435, 440 Impaired glucose tolerance, 440 Impetigo, 191, 664, 664 Impotence, 517 Inadequate bone marrow red cell production, 245 Incarcerated hernia, 361, 363 Incidence, defined, 10 Increased blood bilirubin, 242 Increased intraocular pressure, 693 Incubation period, 197, 402 Incus, 697 Indicator-dilution principle, 71 Indirect contact, 184 Indivisible, defined, 15 Indoor pollutants, 210 Ineffective RBC production, 260 Inefficient pumping stroke, 298 Infarction, 30, 30, 80, 313, 458 Infection, 182, 243, 247, 335, 342, 404, 500, 567 blood markers of, 403 natural course of, 199 Infectious disease, 176–204 agents of, 178 history of fight against, 183 mortality from, 182t Infectious mononucleosis, 136, 251, 251 Infective endocarditis, 312–313 Infertility, 517, 561, 576 Inflammation, 34–50, 43, 44, 44, 159, 279, 517, 519, 643 chain of events in, 37 laboratory indicators, 47 sequence of events in, 42 90981 Index 732 10/12/06 10:19 AM Page 732 Index Inflammatory bowel disease, 374 Inflammatory carcinoma, 574 Inflammatory cells, 39, 45 Inflammatory edema, 72, 74 Inflammatory events, timing of, 41 Inflammatory exudate, 42 Inflammatory myopathies, 164 Inflammatory response, elements of, 36 Inflammatory state, 224 Influenza, 187, 201 Inguinal hernia, 361, 518 Initial functional disorder, defined, Initial structural disorder, defined, Initiating phase, 499 Injured cells, 42 Insulin, 424, 426 Insulinomas, 442 Interatrial septum, 294 Intermittent claudication, 281 Internal hemorrhoids, 371 Internal hydrocephalus, 626 Internal respiration, 325 Interstitial cystitis, 516 Interstitial fibrosis, 335 Interstitial fluid, 69 Interstitial nephritis, 503 Interstitial pneumonia, 339 Interstitial space, 70 Interstitial tissue, 511 Interventricular septal defect, 294 Intervertebral disc disease, 601 Intestinal bleeding, 266, 360 Intestinal phase malabsorption, 374 Intracardiac mural thrombus, 307 Intracardiac thrombus, 78 Intracranial tumors, 641 Intraductal papilloma, 571 Intraductal papillomatosis, 571 Intramembranous ossification, 583 Intraocular pressure, 680 Intrauterine growth restriction, 134 Intravascular coagulation, 76 Intravenously injected illegal drugs, effects of, 220 Intrinsic coagulation pathway, 262 Intrinsic factor, 247 Introitus, 537–538 Intussusception, 361 Ionizing radiation, 92, 465 Iridocyclitis, 687 Iritis, 687 Iron deficiency anemia, 241, 245–246, 246, 266 Irritable bowel syndrome, 371 Irritant contact dermatitis, 662 Ischemia, 25, 80, 499, 630 Ischemic cardiomyopathy, 307, 314 Ischemic heart disease, 302–303, 308 Ischemic optic neuropathy, 693 Islets of Langerhans, 424 Isosporidiosis, 197 IUGR See Intrauterine growth restriction J Jaundice, 135, 392, 395, 395, 396, 396, 402, 412 Jeel-bear, 395 Jejunum, 358, 370 Jock itch, 518 Joint diseases, 594–602 Joint spurs, 596 Juvenile polyps, 380 Juvenile rheumatoid arthritis, 163, 599 Juxtaglomerular apparatus, 480, 483–484 K Kaposi sarcoma, 287, 656, 670 Karyotype, 116, 125 Keloid, 61, 61, 669 Keratin, 364 Keratinocytes, 649 Keratitis, 685 Keratoacanthoma, 668, 668 Keratoconjunctivitis sicca, 684 Keratoconus, 686 Keratopathy of cornea, 686 Kern, 395 Kernicterus, 135, 138, 395 Ketones, 436 Ketonuria, 436 Kidney, 479–508 anatomy of, 482 cyst of, 493 fatty change in, 27 Kinin system, 41 Klinefelter syndrome, 129–130, 130 Korsakoff psychosis, 218 Krukenberg tumor, 563 Kupffer cells, 39, 392 Kussmaul respiration, 436 Kwashiorkor, 222, 222 Kyphosis, 585 L Labia majora, 537 Labia minora, 537 Labile cells, 21, 52 Laboratory findings, 199 Lacerations, 207, 365 Lacrimal apparatus, 684, 685 Lacrimal glands, 679 Lacrimal sac, 679 Lactation, 456 Lacunae, 583 Lamellar bone, 583 Laminar cortical necrosis of brain, 633, 633 Langerhan cells, 649 Lanugo hairs, 652 Large cell carcinomas, 348 Laryngeal papillomas, 330 LDL cholesterol, 275 Lead toxicity, 212–213, 214 Left circumflex coronary artery, 294 Left coronary artery, 294 Left-heart failure, 299, 299, 300 Left-to-right congenital cardiac shunts, 317 Left-to-right shunt, 315 Left ventricle, 293 Left ventricular dilation, 309 Left ventricular hypertrophy, 309 Legionella pneumophila, 340 Leiomyoma, 558, 608 Leiomyosarcoma, 559, 608 Leishmaniasis, 197 Lentigo, 657, 657 Leprosy, 195 Leptin, 225 Lesion, defined, Leukemia, 139, 249, 252, 260 Leukemoid reaction, 251 Leukocyte esterase, 487 Leukocytes, 36, 236 Leukocytosis, 46, 249 Leukodystrophy, 639 Leukopenia, 47, 248 Leukoplakia, 364, 545 Leukorrhea, 549 Lewy bodies, 638 Leydig cells, 514, 520 LGV See Lymphogranuloma venereum Lichen planus, 660, 660 Lichen sclerosus of vulva, 545–546 Lichen simplex chronicus, 545, 658, 659 Lid lag, 460 Light chain disease, 151, 253 Lines of Zahn, 76 Lipase, 423, 430 Lipids, 275 Lipiduria, 492 Lipofuscin, 27 Lipoid nephrosis, 497 Lipoma, 608, 608, 669 Lipoprotein, 275 Liposarcomas, 608 Liquefactive necrosis, 30 Lissencephaly, 624 Listhesis, 601 Liver, 135, 391 See also Alcohol abuse alcoholic, 410 metastatic carcinoma in, 414 Liver cells adenoma, 414 fatty change in, 27 hydropic change, 26 Liver function, 393t Liver function tests, 395 Liver infarcts, 414 Lobar pneumonia, 339 Lobular carcinoma, 572 Long bones, 583 Lordosis, 585 Lou Gehrig disease, 638, 638 Low birth weight, 133–134 Low blood haptoglobin, 242 Low body temperature, 25 Low-grade tumors, 516 Low-protein edema, formation of, 73 Lower esophageal sphincter, 358 Lower gastrointestinal bleeding, 361 Lower limit of normal, defined, Lower respiratory tract, 325 Lower urinary system, 480, 510, 511 Ludwig angina, 607 Lumbar puncture, 635 Lumbosacral plexus, 619 Lumen, 272 Luminal phase malabsorption, 374 Lung abscess, 341 Lupus erythematosus, 266, 530 Luteal cysts, 561 Luteinizing hormone, 458, 514, 540 Lyme disease, 47, 182, 195 Lymph nodes, malignant lymphoma, 255 Lymphadenitis, 46, 251–252 90981 Index 10/12/06 10:19 AM Page 733 Index Lymphadenopathy, 46, 251 Lymphangiomas, 287 Lymphangitis, 46, 185 Lymphatic system, 46, 98 Lymphedema, 72, 74 Lymphocytes, 38, 45–45t, 149t, 236 Lymphocytes-B cells, 149 Lymphocytic leukemia, 172, 249, 252, 253, 256 Lymphocytosis, 47, 251 Lymphogranuloma venereum, 190, 532, 544 Lymphoid cells, 236, 249 Lymphoma, 89, 172, 249 Lymphopenia, 249 Lysosomes, 20 M M-protein, 253 M-spike, 253 Macrocytic anemia, 246 Macroglobulin, 151 Macrophages, 39, 45, 149 Macular degeneration, 680 Mad cow disease, 181 Mainstream smoke, 210 Major blood groups, 152 Major crossmatch, 165 Major histocompatibility complex, 149 Mala aria, 243 Malabsorption syndrome, 374 Malar “butterfly” rash, 163 Malaria, 181, 195, 197, 243, 245 Male genital system, 509–535, 512 Male urinary tract, 481 Malignancy, 153, 561 clinical hallmark of, 99 grading, 102, 104 staging of, 102 Malignant fibrous histiocytoma, 608 Malignant hypertension, 284, 498 Malignant melanoma, 670–671, 672, 673, 695 Malignant nephrosclerosis, 284, 498 Malignant thrombocythemia, 258–259 Malignant tumors, characteristics of, 93t Malleus, 697 Mallory bodies, 27, 409 Mallory-Weiss syndrome, 365, 365 Mallory’s alcoholic hyaline, 409 Malnutrition, 221 Malrotation defects, 315 Mammography, 573 Mantoux skin test, 342, 345 Marasmus, 222 Marfan syndrome, 124, 125–126 Marie-Strümpell disease, 599 Marijuana, 221 Marked generalized edema, 491 Marrow fat, 79 Mastoiditis, 699 mDNA See Mitochondrial DNA Mean cell hemoglobin, 239 Mean cell volume, 239 Mean deviation, Measles, 136 Measurements, defined, Mechanical bowel obstruction, causes of, 362 Meckel diverticulum, 369, 370 Meconium ileus, 138 Medulla, 454, 468 Medulla oblongata, 613, 618 Medullary carcinoma, 465 Medullary cavity, 583 Medulloblastoma, 642 Megacolon, 370 Megakaryocytes, 236 Megaloblastic anemia, 246 Meiosis, 23, 127 Melanin, 649 Melanocytes, 665 Melanoma, 671 Melasma of pregnancy, 652, 657 Melena, 359, 367, 371 Meleney synergistic bacterial gangrene, 193 Membrane factors, 41 Membrane potential, 622 Membranous glomerulonephritis, 496, 496–497 Memory B cells, 149 Memory T cells, 152, 158 MEN syndromes See Multiple endocrine neoplasia syndromes Meninges, 614 Meningioma, 642, 642 Meningitis, 11, 634 Meningocele, 624 Meningomyelocele, 624 Menorrhagia, 555 Menses, 542 Mesangial cells, 484 Mesentery, 358 Mesoderm, 16 Mesothelioma, 349 Messenger RNA, 17, 19 Metabolic processes, 19 Metabolic rate, 452 Metabolic syndrome, 225, 229 Metachromatic leukodystrophy, 639 Metals, 212 Metaphysis, 583 Metaplasia, 29, 29, 31 Metastasis, 98, 347 by seeding, 99 Metrorrhagia, 555 MHC See Major histocompatibility complex Microbes, 160, 182 Microbial culture, 199 Microcephaly, 624 Microcytic hypochromic, 243 Microglia, 39, 622 Microorganisms, 177 Microscopic examination, defined, Microscopic findings, 494 Microscopic hematuria, 487 Microstaging, 673 Microvascular disease, 439 Microvascular injury, 337 Microvilli, 20, 358 Micturition, 510 Midbrain, 613 Middle ear, 696 Migraine, 700 Miliary tuberculosis, 343 Minimal change glomerulonephritis, 496 Minor blood groups, 153 Minor crossmatch, 165 Minor transfusion reaction, 167 733 Miscarriage, 565 Misplaced aorta, 317 Mitochondria, 18–19 Mitochondrial DNA, 20 Mitosis, 20, 23 Mitotic figures, 93 Mitral valve disease, 294, 312, 313 Mixed tumor, 365 Mixed with stool, 359 Molds, 181 Molecular defenses, 146 Molecular density, 275 Molecular mimicry, 160, 161, 310 Molecularly defective, 242 Molecules, 181 Moles, 566–567, 671 Molluscum contagiosum, 532, 545 Moniliasis, 364 Monoclonal gammopathy, 172, 253 Monoclonal spike, 253 Monocytes, 39, 45, 236 Monogenic, 117 Mononuclear cells, 45 Monosomy, 126 Monostotic, 594 Mons pubis, 537 Morbid obesity, 226 Motor unit, 603, 604 Mucinous cystadenocarcinoma, ovary, 563 Mucinous tumors, 561 Mucosa, 538 Mucosa-associated lymphoid tissue, 328, 359 Multifocal leukoencephalopathy, 637 Multinucleated giant cells, 45 Multiple endocrine neoplasia syndromes, 475 Multiple myeloma, 172, 253, 254, 594 Multiple sclerosis, 164 Mumps, 136, 365 Mural thrombus, 305 Muscle, normal, 605 Muscle wasting, 400 Muscular dystrophy, 606, 606 Musculoskeletal disease, 598t Myasthenia gravis, 260, 607 Mycobacterium avium, 172, 194, 341 Mycobacterium leprae, 195 Mycobacterium tuberculosis, 44, 158, 172, 194, 341–342, 343, 345, 589 Mycoplasma, 515–516, 560 Mycoplasma hominis, 531 Mycoplasma pneumoniae, 243, 340 Mycoplasma species, 181, 200, 340 Mycosis fungoides, 670 Myelin, 616, 639 Myelocytic leukemia, 249, 257, 258, 259 Myelodysplasia, 260 Myelofibrosis, 258, 258, 259 Myelogenous leukemia, 257 Myeloid cells, 236, 249 Myeloid leukemia, 258 Myelophthisis, 247 Myeloproliferative disorder, 248, 257 Myocardial infarct, 281, 304, 305–306, 308, 319 Myocarditis, 162, 310, 314 Myocardium, 297 Myometrium, 538 Myopia, 682 90981 Index 734 10/12/06 10:19 AM Page 734 Index Myosin, 603 Myxedema, 460, 462 Myxomatous degeneration of mitral valve, 309 N Narcotic, 220 Narkosis, 220 Nasolacrimal apparatus, 679 Nasolacrimal duct, 679 Nature of disease, 3–6 Nearsightedness, 683 Necrosis, 24, 47 Necrotizing arteriolitis, 284 Necrotizing enterocolitis, 136, 373 Necrotizing fasciitis, 193 Necrotizing vasculitis, 162, 286 Negative feedback loop, 449, 451 Negative tests results, Neisseria gonorrhoeae, 189, 516, 525, 530–531, 544, 600, 684 Neisseria meningitidis, 634 Nematodes, 196 Neonatal cholestasis, 412, 417 Neonatal hepatitis, 412 Neonatal mortality risk, 133 Neoplasms, 86–109, 518, 561 gross structure of, 92 Nephritic syndrome, 487, 491 Nephrolithiasis, 487, 493, 503, 504 Nephron unit, 481 Nephrosclerosis, 283, 499 Nephrosis, 492 Nephrotic syndrome, 487, 491, 492 Nephrotoxic syndrome, 499 Nerve tracts, 613–614 Nervous system, 612–647, 623 Neural hearing loss, 699 Neural tube defect, 113, 624 Neuroblastoma, 475, 643 Neurocutaneous syndromes, 656 Neuroendocrine cells, 454 Neurofibroma, 643, 670 Neurofibromatosis, 124 Neurofibrosarcoma, 643 Neurogenic atrophy, 605 Neurohypophysis, 450 Neuromuscular apparatus, 604 Neuromuscular junction, 603 Neuron, 614 Neurosyphilis, 529 Neurotransmitter, 622 Neutropenia, 249 Neutrophilia, 47, 251 Neutrophils, 36–37, 236 Nevus, 670 Nevus flammeus, 670 New bone formation, 524 Nicotine, 217 See also Smoking Nitrates, 487 Nitric oxide, 41, 275 Nitrogen, 79 Nodular fasciitis, 608 Nodular goiter, 459, 463 Nodular hyperplasia, 521 Nodular lymphoma, 257 Nodular melanoma, 673, 673 Nodular sclerosis Hodgkin lymphoma, 255 Nodular xanthomas, 655 Non-Hodgkin lymphoma, 255–256 Nonbacterial cystitis, 516 Nonbacterial thrombotic endocarditis, 313 Nonendocrine organs, tissues, 451 Nongonococcal infections, 545 Nongonococcal urethritis, 189, 531 Nonimmune antimicrobial protective mechanisms, 147 Noninfective thrombotic endocarditis, 312 Nonneoplastic diseases, 651–665 Nonossifying fibroma of bone, 593 Nonproliferative fibrocystic change, 570 Nonproliferative retinopathy, 691 Nontoxic goiter, 463 Nontropical sprue, 374 Norepinephrine, 454 Normal birth weight, 133 Normal cell, 16 Normal distribution curve, Norwalk virus, 188, 372 Nosocomial infection, 184, 349 Nosomial infection, 341 Nuclear atypia, malignant neoplasms, 93 Nuclear DNA, 18 Nucleotide bases, 17 Nucleus pulposus, 601 Null cell adenoma, 458 Nummular dermatitis, 662 Nystagmus, 682 O Obesity, 222, 224, 229, 435 Obstruction of small blood vessels, 243 Obstructive chronic bronchitis, 334 Obstructive lung disease, 328–329, 331 Obstructive nephropathy, 500 Obstructive sleep apnea, 283 Occult bleeding, 359 Occult blood test, 360 Occult hematuria, 492 Occult proteinuria, 487, 492 Occupational disease, 211 Occupational toxic exposure, 211t Oligodendrocytes, 622, 639 Oligodendroglioma, 641–642 Oligomenorrhea, 555 Oliguria, 490 Omentum, 358 Omphalocele, 370 Onchocerciasis, 686 Oncogenes, 21, 90 Oncology, 87 Oocyte, 539–540 Open-angle glaucoma, 693 Opportunistic infections, 171 Opportunistic pathogens, 172, 193 Optic disc, 682 Optic nerve, 682 Optic neuritis, 693 Oral contraceptives, 214 Oral herpesvirus, 665 Oral hypoglycemic drugs, 442 Orbit, 678, 679 Organ rejection, 164 Organogenesis, 113 Organophosphates, 212 Orthostatic, 490 Osmolality, 485 Osmosis, 67, 68 Osmotic diuresis, 436 Osmotic edema, 72, 74 Osmotic pressure, 67, 74 Ossicles, 697 Osteitis deformans, 585 Osteoarthritis, 595 cartilage damage in, 596 femur head, 596 Osteoblasts, 583 Osteochondroma, 593, 593 Osteoclastoma, 594 Osteocytes, 583 Osteogenesis imperfecta, 585 Osteogenic sarcoma, 593 Osteomalacia, 587, 589, 591 Osteomyelitis, 587 Osteon, 583 Osteophytes, 596 Osteoporosis, 587, 590 causes, consequences of, 590 Osteosarcoma, 585, 593 Otitis externa, 697 Otitis media, 3, 11, 137, 698, 701 Otosclerosis, 699 Ototoxicity, 699 Ovarian cycle, 542 Ovarian cystic teratoma, 564 Ovarian fibroma, 564 Ovarian hormones, 542 Ovarian ligament, 538 Ovarian stromal cell tumors, 563 Ovarian teratomas, 562 Ovarian tumors, 562, 564t Ovaries, 116, 538, 539, 563 bilateral serous cystadenocarcinoma, 563 cystic serous tumor, 563 endometriosis, 556 mucinous cystadenocarcinoma, 563 Overhydration, 71 Ovulatory bleeding, 555 Oxygen, 273 Oxygen superoxide, 41 Oxytocin, 459 P Paget disease, 574, 585 Palmar erythema, 397 Pancreas, 422–447, 424–425 Pancreatic carcinoma, 432 Pancreatic duct, 423 Pancreatic juice, 426t Pancreatic pseudocyst, 428 Pancreatitis, 427, 428, 429, 431 complications of, 432 laboratory tests, 430 pathogenesis of, 428 Panniculitis, 663 Pannus, 597 Pap smear, 102, 102, 549, 551, 552–553, 554 Papillary carcinomas, 465 Papillary dermis, 651 Papillary transitional cell carcinoma, 516 Papilledema, 626, 690, 692 Papilloma, 93 Papillomavirus, 189, 518, 531, 544, 546, 549, 551 90981 Index 10/12/06 10:19 AM Page 735 Index Paragangliomas, 474 Paraganglionic system, 454 Paraneoplastic syndromes, 101, 106, 348 Paraphimosis, 517 Parasitic disease, 47, 189, 195–196t, 251, 372 Parasitos, 195 Parasympathetic system, 619–620 Parathormone, 453 Parenchyma, 16, 93, 392 Paresis, 529, 529 Parietal epithelial cells, 484 Parkinsonism, 637–638 Partial thromboplastin time, 262 Passive congestion, 74, 414 Passive immunity, 151 Patent ductus arteriosus, 316 Patent foramen ovale, 316 Pathogenesis, defined, Pathologic fracture, 586 Pathologic uterine bleeding, 555 Pathophysiology, defined, Patient compliance, 288 Peau d’orange, 74 Pediatric disease, 110–234 Pedunculated tubular adenomas, colon, 381 Pelvic inflammatory disease, 560 Pelvic relaxation syndrome, 560 Pelvis, 540 Pemphigoid, 659 Pemphigus, 659, 659 Pemphix, 659 Penetrance, 120 Penis, 510 Bowen disease, 518 chancre, 527 Pepsin, 358 Pepsinogen, 358 Peptic ulcer, 189, 367–368, 368 Peptides, 357 Perforated peptic ulcer, stomach, 369 Periapical abscess, 363 Pericardial effusion, 319 Pericarditis, 310, 319, 490 Periodontitis, 363 Periosteum, 583 Peripheral nervous system, 490, 613, 618, 620 Peripheral neuropathy, 440 Peripheral vascular insufficiency, 281 Peristalsis, 355 Peritoneal effusions, 302 Peritonitis, 379 Permanent cells, 54 Pernicious anemia, 247 Persistent chronic inflammation, 45 Persistent proteinuria, 490 Petechiae, 75, 314 Petroleum products, 212 Peyer patches, 359 Peyronie disease, 517–518 Phagocytes, 45 Phagocytosis, 20, 37, 40 Pharyngitis, 330 Phenotype, 116 Pheochromocytoma, 101, 284, 474 Phimosis, 517 Photoaging of skin, 652, 660, 661 Photosensitivity, 652 Phototherapy, 135 Phylaxis, 154 Phyllodes tumor of breast, 571, 572 Physiologic jaundice, 135, 412 Physiologic proteinuria, 490 Pia mater, 614 Pickwickian syndrome, 227 PID See Pelvic inflammatory disease Pigment gallstones, 415 Pigment stones, 416 Pigmented villonodular synovitis, 602 Pinguecula, 683 Pinworm, 196 Pitting, low-protein edema, 73 Pituitary adenoma, 455, 455 Pituitary gland, 451, 456t Pituitary hormones, 452t, 542 Pituitary stalk, 450 Placenta, 134 Placenta accreta, 566 Placenta previa, 566 Plague, 195 Plaque, 304, 363 Plasma, 89, 235 Plasma cell diseases, 39, 252 Plasma cells, 45, 149, 252 Plasma-derived, 40 Plasma lipids, 275 Plasma membrane, 20, 21 Plasma proteins, 40 Plasmodium falciparum, 242, 245 Plasmodium species, 195, 245 Platelet abnormalities, 76 Platelet count, 263 Platelet function analysis, 263 Platelets, 236, 312 Pleomorphic adenoma, 365 Pleural effusion, 302, 349 Pleurisy, 341, 349 Pleuritis, 349 Pnein, 283 Pneumoconiosis, 215, 336 Pneumocystis, 193 Pneumocystis jiroveci, 172, 172, 181, 193, 346, 347 Pneumocystis pneumonia, 346 Pneumocytes, 327 Pneumonia, 339–340, 349 Pneumothorax, 349 Podagra, 600 Point mutation, 118 Poisoning Pollutants, 210 Polyarteritis nodosa, 164, 286 Polycystic disease, 493 Polycystic ovary syndrome, 561 Polycythemia vera, 248, 257, 259 Polydactyly, 114 Polydipsia, 436 Polygenics, 117–118 Polyhydramnios, 624 Polymenorrhea, 555 Polymorphonuclear leukocytes, 37 Polymyalgia rheumatica, 48, 600 Polymyositis, 607, 607 Polyphagia, 436 Polyps, 93 Polyuria, 436 735 Pontine hemorrhage, 626 Portal cirrhosis, 397–398 Portal hypertension, 398, 399, 400 Portal triads, 392 Portal venous system, 390, 391 Positive test results, defined, Postadolescent acne, 663 Posterior descending coronary artery, 294 Postinflammatory pigmentation, 658 Poststreptococcal glomerulonephritis, 494 Postural hypotension, 440 Postural proteinuria, 490 Potassium hydroxide test, 665 Pre-eclampsia, 568 Prehepatic jaundice, 395 Preleukemia, 260 Premalignant conditions, 92, 95, 549 Premature atrial contractions, 298 Premature birth, 134, 140 Premature ventricular contractions, 298 Prenatal specimen collection, genetic diagnosis, 131 Prepuce, 510 Presbus, 683 Presbyopia, 683 Presumably healthy, defined, Pretibial myxedema, 459, 654 Priapism, 518 Priapus, 518 Primary progressive tuberculosis, 342–343 Primary sclerosing cholangitis, 413 Proctitis, 193 Prodromal period, 197 Produces sputum, 333 Progeria, 24 Programmable, 147 Prolactinoma, 456 Proliferative breast disease, 570–571 Proliferative fibrocystic change, 570 Proliferative phase, 542 Proliferative retinopathy, 691 Proliferative synovitis, 597 Propionibacterium acnes, 177, 663 Proprioceptive sense, 613 Proptosis, 684 Prostate, 514 anatomy, 521 nodular hyperplasia of, 522 Prostate-specific antigen, 106, 524 Prostatic adenocarcinoma, 521 Prostatitis, 520 Proteases, 423 Protein, 17, 222, 357 Protein electrophoresis, 253, 254 Protein-energy malnutrition, 222 Protein synthesis, 19, 399 Proteinuria, 486, 490–491 Prothrombin time, 262 Proto-oncogenes, 21, 56, 90, 124 Protozoa, 197, 372 Pseudarthrosis, 587 Pseudofolliculitis barbae, 654 Pseudomembranous colitis, 193, 372 Pseudomonas, 193–194, 340 Psoriasis, 658, 658 Psoriatic arthritis, 600 Pterygium, 684 PTT See Partial thromboplastin time 90981 Index 736 10/12/06 10:19 AM Page 736 Index Pulmonary arteriole, pulmonary hypertension, 338 Pulmonary artery, rechanneled, 79 Pulmonary atresia, 319 Pulmonary congestion, 340 Pulmonary edema, 74, 299–300, 337 Pulmonary hyaline membranes, 135 Pulmonary hypertension, 337, 338 Pulmonary infarct, 337 Pulmonary interstitium, 328 Pulmonary membrane, 328 Pulmonary surfactant, 327 Pulmonary thromboembolism, 79, 337 Pulmonary tuberculosis, 346 Pulmonary valve, 294 Pulmonary valve stenosis, 317 Pupil, 679 Pure cholesterol stones, 415 Purpura, 75 Purulent meningitis, 634 Purulent otitis media, 699 Pyelonephritis, 502–503, 503 Pyloric sphincter, 358 Pylorus, 358 Pyogenic granuloma, 61, 669 Q Qualitative defect, 591 Quantitative defect, 589 R Radial growth phase, 673 Radiant energy spectrum, 215t Radiation, ionizing, 465 Radioactive bone scan, 525 Radioactive iodine uptake, 461 Radon, 210 Rapidly progressive glomerulonephritis, 495 Raynaud phenomenon, 164 RDS See Respiratory distress syndrome Reactant proteins, 46 Reactive arthritis, 599 Reactive hyperplasia, 46, 251 Reactive hypoglycemia, 442 Reactive lymphadenitis, 251 Reactive oxygen compounds, 41 Reagins, 529 Receptors, 123, 149 Recessive genes, 119 Recipient RBC, 165 Recovery from injury, 51–64 Rectocele, 560 Red blood cell antigens, and agglutinins, 152t Red blood cells, 236, 239, 239, 241, 259 Red marrow, 583 Red stroke, 627, 630 Reed-Sternberg cell, 255 Reflux esophagitis, 366 Reflux nephropathy, 500 Refractive disorders, 682, 683 Refractive errors, 682, 687 Refractory anemia, 260 Regeneration, 52, 57 Regional enteritis, 374 Reiter syndrome, 190 Relative risk, absolute risk, distinguished, 571 Renal ablation glomerulopathy, 498, 500 Renal adenocarcinoma, 505 Renal agenesis, 493 Renal cell carcinoma, 505, 506 Renal colic, 493 Renal disease, 284 Renal dysplasia, 493 Renal failure, 486–487, 492, 591 Renal pelvis, 480, 504 Renal tubules, 480, 483 Renin, 274, 480–481, 483–484 Renin-angiotensin-aldosterone system, 300, 469, 484 Renovascular hypertension, 499 Renovascular insufficiency, 281 Reservoir, 184 Resorption atelectasis, 331 Respiration, 325, 436 Respiratory distress syndrome of adults, 135 Respiratory distress syndrome of neonates, 140 Respiratory infections, 187, 330 Respiratory syncytial virus, 136–137 Respiratory system, 324–353, 326 Restrictive disease, 328–329 Restrictive lung disease, 335 Retention polyps, 380 Reticular dermis, 651 Reticulocytes, 239 Retina, 680 in diabetes, 691 in hypertension, 690 normal, 681 Retinal detachment, 689, 689 Retinal occlusive vascular disease, 690 Retinal vascular disease, 690 Retinitis pigmentosa, 692 Retinoblastoma, 100, 695 Retinopathy, 136, 692 background, 691 Retrograde ejaculation, 517 Retroperitoneum, 510 Retropharyngeal abscess, 607 Reye syndrome, 214 Rhabdomyolysis, 607 Rhabdomyoma, 608 Rhabdomyosarcoma, 608 Rheumatic fever, 309–310 Rheumatic heart disease, 309, 311 Rheumatic valvulitis, 310, 312 Rheumatoid arthritis, 163, 596–597, 598, 599 Rheumatoid factor, 163, 597 Rheumatoid nodules, 163, 597, 598 Rheumatoid spondylitis, 599 Rhinovirus, 187 Ribosomal RNA, 17, 19 Ribosomes, 19 Rickets, 222, 591 Rickettsia species, 181, 195, 200, 340 Right atria, 293 Right coronary artery, 294 Right-heart failure, 300 Right middle lobe syndrome, 331 Right-to-left shunts, 315–316 Right ventricle, 293 Right ventricular heart failure, 300 Right ventricular hypertrophy, 317 Ringworm, 518 RNA synthesis, 17, 18, 19 Rocky Mountain spotted fever, 195 Rods, 680 Rosacea, 663 Rotavirus, 188, 372 Rough endoplasmic reticulum, 20 Round ligament, 538 Round window, 697 Roundworms, 196 RSV See Respiratory syncytial virus Rubella, 136 Rule of nines, 208 Ruptured mitral valve chordae tendineae, 309 S Saccharides, 357 Saccular aneurysm, 629, 629 Saddle embolus, 337 Salicylism, 214 Salmonella species, 164, 189, 200, 243, 372 Salmonellosis, 372 Salpingitis, 560, 576 Salt wasting, 472 Salt water therapy, 72 Sarcoidosis, 656 Sarcomas, 88–89, 572, 608 Saturation, 245 Scar development, 44–45, 47, 57, 57 Scarlatina, 191 Scarlet fever, 191 Schistosoma, 196 Schistosomiasis, 182, 196 Schlemm’s canal, 680 Schwann cells, 622 Schwannomas, 643 Sciatica, 601 SCID See Severe combined immunodeficiency Sclera, 678, 685 Scleral icterus of jaundice, 395 Scleroderma, 164, 164, 660 Sclerosing cholangitis, 376–377, 398 Sclerosing panencephalitis, 637 Sclerosis, 164, 164, 277, 639 Scrotum, 513 Seborrheic dermatitis, 658, 658 Seborrheic keratosis, 666, 667 Secondhand smoke, 210 See also Smoking Seeding, 98, 99 Sella turcica, 450 Semen, 513 Semicircular canals, 697 Seminal vesicles, 511 Seminiferous tubules, 511 Seminoma, 519, 520 Semipermeable membrane, 67–68 Sensitive tests, 10 Sensitivity, 307 defined, specificity, distinguished, Sensory hearing, 699 Septal defects, 315 Septic arthritis, 600 Septic shock, 81 Septicemia, 191, 199 Septum, 315 Serologic tests, 530 Seronegative spondyloarthropathies, 164, 599 Serous cystadenocarcinoma, 563 Serous effusions, 162 Serous inflammation, 42 90981 Index 10/12/06 10:19 AM Page 737 Index Serous otitis media, 698 Serous tumors, 561 Sertoli cells, 511 Severe combined immunodeficiency, 168 Sex chromosomes, 116 Sex-linked recessive, 119 Sexually transmitted disease, 189, 525–526t, 544–544t, 576 prevention of, 525 Sheehan syndrome, 458, 458 Shigella species, 164, 189, 200, 372, 599 Shock, 83 stages of, 82 Short bones, 583 Shortness of breath, 266–267 Sialadenitis, 365 Sickle cell disease, 242, 242, 243, 244 Sickle cell trait, 242 Sickness, defined, Sidestream smoke, 210 SIDS See Sudden infant death syndrome Signs, defined, Silicosis, 336 Simple cysts, 493 Simple fracture, 586 Simple hyperplasia, 557 Singer’s nodes See Vocal cord nodules Single gene, 117 Sinoatrial node, 295 Sjögren syndrome, 164, 365, 684 Skeletal muscle, 581–650 Skin, 648–673 neoplasms of, 665–677 normal, 650–651 pigmentation, 657 Skin burns, pathology of, 209 Skin lesions, 162 types of, 653 Skin tag, 665, 665 Skin wart, 666 Skull fracture, 627 SLE See Systemic lupus erythematosus Small bowel, Crohn disease, 376 Small cell carcinomas, 347–348 Small cell lymphocytic lymphoma, 252, 256 Small pulmonary artery, 317 Small vessels, 286, 439 Smoking, 279, 333, 349 effects of, 201, 216 lung cancer, relationship, 217 Smoldering leukemia, 260 Smooth endoplasmic reticulum, 20 Smooth muscle cells, 273, 279 Soft callus, 587 Solar keratosis, 667, 667 Somatic cells, 116, 118 Somatostatin, 358, 424, 426 Somatotropin adenoma, 456 Specificity, defined, Sperm, 514 Spermatic cord, 511 Spermatocele, 518 Spermatocyte, 511 Spermatogenesis, 513 Spermatozoa, 513 Spider angiomas, 652, 670 Spider angiomata, 397 Spider bite, 532–533 Spina bifida, 113, 624 Spinal cord, 618 Spinal curvature, abnormalities of, 585 Spinal nerves, 618 Spine, osteoporosis, 590 Spiral fracture, 586 Spirochetes, 177 Spirography, 329 Spirometry, 328, 333, 335 Spleen, 260 Splenomegaly, 260, 398 Spondylitis, rheumatoid, 599 Spondyloarthropathy, 163–164, 599 Spondylolisthesis, 601 Spondylos, 599, 601 Spongiform encephalitides, 637 Spontaneous subarachnoid hemorrhage, 629 Sporadic goiter, 463 Sprain, 601 Sprue, 374 Squama, 16, 649 Squamocolumnar junction, 538, 546 Squamous cell carcinoma, 16, 348, 364, 366, 544–545, 552, 669, 697 Stable angina, 304 Stable cells, 52 Staghorn calculus, 504 Stalk effect, 455 Standard deviation, Stapes, 697 Staphylococcus species, 26, 43, 177, 185, 191, 193, 340–341, 587, 664 Stasis dermatitis, 287, 660, 661 Statin drugs, 281 Statistical evidence, 347 Status asthmaticus, 332 Stein-Leventhal syndrome, 561 Stem cells, 29, 52–53, 54 Stenosis, 370 Sterile peritonitis, 379 Sternum, chondrosarcoma of, 593 Steroid therapy, 659 Stevens-Johnson syndrome, 660 Still disease, 163 Stimulants, 220 Stokes-Adams seizure, 298 Stomach, peptic ulcer, 368–369 Stones, 415, 416, 504 Stool occult blood test, 360, 382 Strabismus, 682 Strain, 601 Strangulated hernia, 361 Stratum corneum, 649 Streptococcal diseases, 192 Streptococcal pharyngitis, 191, 506 Streptococcus species, 137, 186, 191, 313, 339–340, 634 Stress fracture, 586 Stress ulcers, 367 Striae, 652 Stroke, 281, 288, 627, 631, 644 Stromal dystrophy, 686 Structural disorder, defined, Structure, defined, Sty, 684 Subacute sclerosing panencephalitis, 637 Subarachnoid hemorrhage, 627–628 737 Subarachnoid space, 614 Subconjunctival hemorrhage, 684 Subcutaneous tissue, 651 Subdivisions of chromosome, 17 Subdural hematoma, 627, 628–629 Subendocardial infarct, 305 Subluxation, 601 Sudden infant death syndrome, 137 Sugars, 357 Sunburn, 652 Superficial spreading melanoma, 673 Superficial ulcers, 367 Superior sagittal sinus, 614 Suppressor T cells, 152, 160 Suppurative inflammation, 43 Surface epithelial cells, 538 Suspensory ligaments, 679 Sweat chloride test, 138 Swimmer’s ear, 698 Sympathetic chain, 620 Sympathetic fibers, 620 Sympathetic ophthalmitis, 688 Symptoms, defined, Synapse, 603, 622 Synaptic space, 603, 622 Syndactyly, 114 Synechiae, 688 Synovial joint, 594, 595 Synovial sarcoma, 608 Syphilis, 47, 189, 525, 527–530, 544 condyloma lata of, 528 serologic tests for, 530 Syphilitic aneurysm, 285 Syphilitic aortitis, 309, 528 Syphilitic meningitis, 634–636 Systemic anaphylaxis, 159 Systemic lupus erythematosus, 160, 163, 656, 660 Systemic sclerosis, 164, 164 T T-cell receptor, 152 T cells, 148t–149t, 152, 160 Tabes dorsalis, 529 Tachycardia, 297 Takayasu aortitis, 286 Tapeworms, 196 Tarsal plate, 678 Tartar, 363 TB See Tuberculosis TBG See Thyroxine binding globulin Telangiectasis, 670, 670 Telogen effluvium, 654 Telogen phase, 652 Temporal arteritis, 286, 601 Tendinitis, 602 Tendon, 601 Tenosynovitis, 602 Tentorial herniation, 625 Tentorium, 614 Teras, 114 Teratogen, 114 Teratoid, 114 Teratoma, 562 Terminal ileitis, 374–375 Tertiary hyperparathyroidism, 467 Test results, positive, defined, Test sensitivity, specificity, 11–12 90981 Index 738 10/12/06 10:19 AM Page 738 Index Test usefulness, effect of disease prevalence on, 10 Testicular atrophy, 397 Testicular cancer, 520 Testicular neoplasms, 519 Testis, 116, 511, 513, 518, 518 seminoma, 520 undescended, 518 Testosterone, 511, 513–514 Tests in diagnosis, usefulness of, 8–12 highly sensitive, defined, 10 highly specific, defined, 10 sensitive, 12 Tetanus, 193, 607 Tetraiodothyronine, 452 Tetralogy of Fallot, 317, 318 Thalassemia, 242–243 Thalassemia major, 243 Thalassemia minor, 243 Theca cells, 539 Thromboangiitis obliterans, 286 Thrombocythemia, essential, 259 Thrombocytopenia, 75–76, 264 Thrombocytosis, 259 Thromboembolism, 78–79 Thrombophlebitis, 78, 287 Thrombosis, 265, 304, 304 Thrombotic endocarditis, nonbacterial, 313 Thrombus formation, 76, 77–78, 79, 280 Thrush, 346, 364 Thymic hypoplasia, 168 Thymus, 260 Thyroglobulin, 452 Thyroglossal duct cyst, 114 Thyroid adenoma, 464 Thyroid cancer, 465 Thyroid function, 462t, 654 Thyroid gland, 463 hyperthyroidism, 460 Thyroid hormone, 453 Thyroid-stimulating hormone, 460 Thyroid stimulating hormone adenoma, 458 Thyroid-stimulating immunoglobulin, 459 Thyroiditis, 462–463 Thyrotoxicosis, 459 Thyrotropin-releasing hormone, 450 Thyroxine, 452 Thyroxine binding globulin, 453 TIBC See Total iron binding capacity Tics, 47, 182, 195 Tinnitus, 699 Tissue organization, 17–18 Tobacco smoking, 201, 216, 279, 333, 349 lung cancer, relationship, 217 Tonsillar herniation, 625 Topical steroid therapy, 659 TORCH syndrome, 115, 115 TORCH teratogens, 114 Total blood volume, 71 Total cholesterol, 275 Total iron binding capacity, 245 Total plasma cholesterol, 276 Total red cell mass, measurement of, 248 Toxemia, 568 Toxic epidermal necrolysis, 660 Toxic goiter, 463 Toxic megacolon, 377 Toxoplasma gondii, 193, 687 Toxoplasmosis, 193 Trachoma, 195, 684 Transfer RNA, 17, 19 Transferrin, 245 Transformation zone, 548 Transfusion reaction, 165–166 Transient ischemic attack of brain, 632 Transitional cell carcinoma, 506, 516 Transitional cells, 510 Transitional epithelium, 516 Transmural infarct, 305 Transplant rejection, 164 Transport proteins, 123 Transposition of great vessels, 318 Transudate, 72, 349 Trauma, 207, 643 mortality, U.S., 207 Trematodes, 196 Treponema pallidum, 44, 527–529, 531 Trichina species, 196 Trichinella, 606 Trichinosis, 196, 606 Trichomonas vaginalis, 47, 181, 197, 531, 545 Trichomoniasis, 191, 197, 545 Tricuspid valve, 294 Triglyceride, 275 Trisomy, 127 Tropical diseases, 194 Tropical sprue, 374 True negative, True positive, Trypanosomiasis, 197 Tuberculin skin test, 345 Tuberculosis, 341–342, 343, 344, 346 See also Mycobacterium tuberculosis atypical, 194 natural history of, 343 secondary, 344 Tuboovarian abscess, 560, 560 Tubular adenoma of colon, 380 Tubular epithelium, 483 Tubular necrosis of kidney, 492, 499, 499 Tubular processing, glomerular filtrate, 485 Tubulointerstitial nephritis, 493–494, 500, 500 Tumor cell heterogeneity, 98 Tumor-cell heterogeneity, 97 Tumor doubling time, 96 Tumor growth fraction, 96 Tumor suppressor genes, 21, 91, 124 Tunica albuginea, 518 Tunica vaginalis, 513 Turner syndrome, 130–131, 131, 555 Tuskegee syphilis experiment, 529 Tympanic cavity, 696 Tympanic membrane, 696 Typhoid fever, 189, 372 U Ulcerative colitis, 164, 374, 375, 376 colon in, 376–377 complications of, 378 Crohn disease, 375t Uncompensated failure, 299 Unconjugated bilirubin, 392, 395 Undescended testis, 518, 518 Unstable angina, 304 Upper gastrointestinal bleeding, 359–361 Upper respiratory tract, 187, 325 Upper urinary tract, 480, 510 Urea, 485 Uremia, 487, 490 Ureterovesical junction, 502, 510, 515 Ureterovesical urine reflux, 515 Ureters, 480 Urethral exudate, gonorrhea, 531 Urethritis, 516 Urinalysis, 487, 489 Urinary obstruction, 500, 501, 522 Urinary reflux, 500 Urinary sediment, 489 Urinary space, 484 Urinary tract syndromes, 487, 491t, 492 male, 481 neoplasms of, 505 Urine, 481, 483, 485 dark, 506–507 Urobilinogen, 392 Urolithiasis, 493 Urticaria, 159, 661 Urticarial wheals, 661 Uterine infection, 140 Uterine prolapse, 560 Utero obstruction, urinary flow, 493 Uterosacral ligament, 538 Uterus, 538, 539, 558, 560 Uveal tract, 682, 687, 688 Uveitis, 687, 688 V Vagina, 538, 539 Vaginal speculum, 551 Vaginitis, 545 Valine, 118 Valley fever, 346 Valve disease, 310 Valvular insufficiency, 309, 313 Valvular stenosis, 309 Valvulitis, 310 Varicella-zoster virus, 137 Varicocele, 517–518 Varicose vein, 74 Varix, 365 Vas deferens, 511 Vascular endothelial growth factor, 56 Vascular malformation, 629–630 Vascular resistance, 273 Vasculitis, 286 Vasoactive amines, 41 Vasoconstriction, 273 Vasodilation, 81, 273 Vasogenic edema, 626 Vellus hairs, 652 Ventricles, 614 Ventricular fibrillation, 298, 309 Ventricular septal defect, 316–317, 318 Ventricular tachycardia, 298 Verruca vulgaris, 666, 666 Vertebral body, collapse fracture of, 591 Vertical growth phase, 673 Vestibular neuronitis, 699 Vibrio cholerae, 189, 372 90981 Index 10/12/06 10:19 AM Page 739 Index Villi, 358 Villonodular synovitis, 602 Villous adenoma, 380 Viral encephalitis, 637 Viral hepatitis, 398, 401–402 Viral meningitis, 634 Visceral epithelial cells, 484 Vitamin B12, 246, 246 Vitiligo, 657, 657 Vitreous chamber, 680 Vitreous detachment, 689 Vitreous hemorrhage, 689 Vitreous humor, 680 Vocal cord nodules, 330 Volatile organic compounds, 212 Volume depletion, 436 Volvulus, 361, 370, 370 Vomit, 359 Von Recklinghausen disease, 124, 643, 644 Von Willebrand disease, 264 VSD See Ventricular septal defect Vulvar dysplasia, 546 Vulvar intraepithelial neoplasia, 546 Vulvar squamous dysplasia and malignancy, 546 W Waldenstrom macroglobulinemia, 253 Wart, 191, 531, 666, 666 Waterhouse-Friderichsen syndrome, 472 Weber-Christian disease, 663 Wegener granulomatosis, 286 Wens, 665 Werner syndrome, 24 Wernicke encephalopathy, 218 Western Equine fever, 637 Wheals, urticarial, 661 White blood cells, 36, 236–239 White matter, 616, 622 White stroke, 627, 630, 632 Whiteheads, 663 Whole chromosomes, 117 Whooping cough, 137 Wilson disease, 412 Woven bone, 583 X X chromosome, 122 X-linked agammaglobulinemia, 167 X-linked recessive gene inheritance, 122, 123 X-rays, discovery of, 586 Xanthelasma, 655 Xanthomas, 396, 655 eruptive, 655 fibrous, 608 nodular, 655 Xeroderma pigmentosa, 91 Xerostomia, 365, 684 Xerotica obliterans, balanitis, 517 Y Yeast, 181 Yeast-like fungi, 346 Yellow marrow, 583 Yersinia enterocolitica, 372 Yersinia pestis, 195 Yolk sac carcinoma, 520 Z Z deformity, 597 Zahn, lines of, 76 Zollinger-Ellison syndrome, 369, 442 Zymogens, 423 739 ... people, one of the ducts usually drains only a small part of the pancreas and empties directly into the duodenum The other duct drains most of the pancreas but is often too small for the job, predisposing... pancreatic duct merges with the common bile duct, and together they pass through the head of the pancreas before emptying into the duodenum at the ampulla of Vater The pancreas is exceptional... excretion of bile acids (made from cholesterol) from the liver into the intestine and the reabsorption of most of the bile acids (and their cholesterol) by the intestine for recirculation through the