(BQ) Part 2 book Lippincott''s illustrated Q&A review of histology presents the following contents: Liver, biliary system and pancreas; urinary system, female reproductive system and breast, endocrine system, special sense organs, comprehensive review, introduction to histopathology.
Chapter 14 Liver, Biliary System, and Pancreas QUESTIONS Select the single best answer You are asked to discuss the gross and microscopic anatomy of the liver during a pathology conference Classic liver lobules are described as hexagonal prisms that surround which of the following anatomic structures? (A) Bile duct (B) Central vein (C) Hepatic artery (D) Portal triad (E) Portal vein A different visual field from the slide described in Question is examined at the same magnification Identify the structures indicated by the arrows (shown in the image) A liver biopsy is examined at a multiheaded microscope in the pathology department The surgical pathologist asks you questions to assess your understanding of normal liver histology Identify the structure within the circle (shown in the image) (A) Arcuate arteries (B) Hepatic arteries (C) Interlobular arteries (D) Sublobular veins (E) Terminal hepatic venules A neonate born prematurely at 32-weeks’ gestation develops yellow skin and sclera (physiological jaundice) Laboratory studies show elevated serum levels of bilirubin (breakdown product of heme) Inadequate bilirubin clearance by the liver in this neonate was most likely caused by organ immaturity What liver enzyme conjugates serum bilirubin, making it water soluble, for excretion in the bile? (A) Alanine aminotransferase (B) Aspartate transaminase (C) Fatty acyltransferase (D) Galactosyltransferase (E) Glucuronyltransferase (A) Bile duct (B) Central vein (C) Hepatic artery (D) Portal triad (E) Portal vein 190 0002076927.INDD 190 3/19/2014 3:01:25 PM Liver, Biliary System, and Pancreas A 75-year-old man with congestive heart failure complains of increasing shortness of breath On physical examination, the patient has an enlarged and tender liver and swollen legs Increased venous pressure due to right-sided heart failure primarily affects which of the following regions of this patient’s liver? (A) Centrilobular hepatocytes (B) Periportal hepatocytes (C) Intrahepatic bile ducts (D) Extrahepatic bile ducts (E) Portal vein Digital slides of the liver and the biliary system are examined in the histology laboratory The sinusoids within this liver lobule (arrows, shown in the image) receive most of their blood from which of the following sources? 191 (A) Fenestrations (B) Glycogen inclusions (C) Secretory granules (D) Slit-pore diaphragms (E) Stereocilia Your laboratory instructor asks you to discuss endocrine, exocrine, absorptive, and secretory functions of the liver Secreted proteins such as albumin, clotting factors, and nonimmune globulins enter what microscopic cavity before entering the liver sinusoid? (A) Duct of Santorini (B) Duct of Wirsung (C) Rokitansky-Aschoff sinus (D) Space of Disse (E) Space of Mall During a clinical conference, you are asked to discuss iron storage disorders affecting the liver You explain that iron overload can occur due to increased breakdown of erythrocytes (hemolysis) or increased intestinal absorption Name the principal iron storage pigment found in hepatocytes (A) Bilirubin (B) Cytochromes (C) Hemoglobin (D) Hemosiderin (E) Transferrin (A) Arcuate artery (B) Hepatic artery (C) Interlobular artery (D) Portal vein (E) Sublobular vein The arrows on the image provided for Question point to the nuclei of endothelial cells that line the hepatic sinusoids Which of the following cytologic features best characterizes these squamous epithelial cells? 0002076927.INDD 191 10 A 5-year-old girl presents with yellow skin and sclerae The parents believe that she recently swallowed a bottle of acetaminophen tablets A liver biopsy reveals hepatic necrosis Which of the following enzymes metabolized acetaminophen and generated toxic metabolites in the liver of this young patient? (A) Catalase (B) Cytochrome P450 (C) Myeloperoxidase (D) NADPH oxidase (E) Superoxide dismutase 3/19/2014 3:01:27 PM 192 Chapter 14 11 Phagocytic cells in the liver of an experimental animal are studied using carbon particles as a vital marker Five hours after intravenous injection of India ink, the animal is sacrificed and the liver is processed for light microscopy The black cells shown in the image represent Kupffer cells (macrophages) that have internalized carbon In addition to foreign particles, Kupffer cells internalize and degrade which of the following components of portal venous blood? (A) Blood products from the spleen (B) Chylomicrons and lipid micelles from the gastrointestinal tract (C) Endocrine secretions from the pancreas (D) Nutrients from the gastrointestinal tract (E) Toxins from the gastrointestinal tract 12 A 40-year-old woman presents with an 8-month history of generalized itching, weight loss, fatigue, and yellow sclerae Physical examination reveals mild jaundice A liver biopsy discloses bile duct injury and inflammation Which of the following cells forms the lining epithelium of the biliary tree? (A) Cholangiocytes (B) Endothelial cells (C) Hepatic stellate cells (D) Hepatocytes (E) Kupffer cells 13 A 50-year-old malnourished man presents with a 6-month history of night blindness Physical examination reveals corneal ulceration The patient is subsequently diagnosed with vitamin A deficiency Which of the following cells in the liver stores vitamin A as retinyl esters? (A) Cholangiocytes (B) Endothelial cells (C) Hepatic stellate cells (D) Hepatocytes (E) Kupffer cells 0002076927.INDD 192 14 Virtual microscope slides illustrating the liver and the biliary system are examined in the histology laboratory Identify the structure indicated by the arrow (shown in the image) (A) Bile duct (B) Central vein (C) Hepatic artery (D) Interlobular artery (E) Portal vein 15 Injury or inflammation affecting the canal of Herring in the liver lobule is associated with which of the following pathologic changes? (A) Fat droplets within hepatocytes (B) Fibrosis of the common bile duct (C) Gallstones (cholelithiasis) (D) Hypertrophy of smooth muscle in the ampulla of Vater (E) Intrahepatic bile lakes 16 One of your classmates casually mentions that the liver produces about L of bile per day As you attempt to confirm this surprising information through independent study, you learn that cholangiocytes continuously monitor the flow of bile What subcellular organelle is sensitive to the directional flow of bile in the biliary tree? (A) Cilia (B) Flagella (C) Hemidesmosomes (D) Microvilli (E) Stereocilia 3/19/2014 3:01:29 PM Liver, Biliary System, and Pancreas 193 17 A liver biopsy from a 62-year-old alcoholic man discloses regenerative liver nodules surrounded by fibrous scar tissue (histologic features of cirrhosis) The surgical pathologist asks you to comment on the remarkable capacity of the liver to regenerate Hepatic stem cells that contribute to liver regeneration reside in which of the following locations? (A) Canal of Herring (B) Glisson capsule (C) Hepatic sinusoid (D) Space of Disse (E) Space of Mall 18 A 40-year-old woman with a history of indigestion inquires about the location of her gallbladder She also asks for information regarding risk factors for gallstones What normal component of bile is associated with the pathogenesis of gallstones? (A) Bicarbonate (B) Cholesterol (C) Cholic acid (D) Mucin (E) Sodium chloride 19 A 52-year-old woman presents with a 10-month history of upper abdominal pain after fatty meals An ultrasound examination discloses multiple echogenic objects in the gallbladder (gallstones) The gallbladder is removed (cholecystectomy), and the surgical specimen is examined by light microscopy Identify the normal epithelial structures indicated by the arrows (shown in the image) (A) Adventitia (B) Lamina propria (C) Muscularis externa (D) Serosa (E) Submucosa 21 Concentration of bile salts and pigments within the lumen of the gallbladder depends on active transport of Na+ and HCO3−, as well as passive transport of H2O Which of the following proteins facilitates the passive transport of water across the plasma membrane of epithelial cells lining the gallbladder? (A) Aquaporin (B) Cadherin (C) Occludin (D) Perforin (E) Porin 22 Various peritoneal and retroperitoneal organs are examined using virtual microscope slides in the histology laboratory Identify the organ shown in the image (A) Canals of Herring (B) Hepatic ducts (C) Mucosal folds (D) Mucosal glands (E) Submucosal glands 20 The surgical pathologist shows you another gallbladder for comparison (shown in the image) In contrast to other organs in the gastrointestinal system, the wall of the gallbladder lacks which of the following layers? 0002076927.INDD 193 (A) Gallbladder (B) Liver (C) Pancreas (D) Parotid gland (E) Submandibular gland 3/19/2014 3:01:33 PM 194 Chapter 14 23 The organ identified in Question 22 is examined at high magnification Which of the following terms describes the glandular epithelial cells shown in the image? (A) Intercalated duct (B) Interlobular duct (C) Intralobular duct (D) Main pancreatic duct (E) Rokitansky-Aschoff sinus 26 During a small group seminar, you are asked to discuss pancreatic enzymes and their role in the digestion of food Which of the following enzymes catalyzes the conversion of pancreatic proenzymes to active enzymes within the lumen of the duodenum? (A) Alkaline phosphatase (B) Elastase (C) Maltase (D) Phospholipase (E) Trypsin (A) Endocrine (B) Goblet (C) Mucous (D) Paracrine (E) Serous 24 The pancreas delivers an alkaline pH fluid to the duodenum that helps to neutralize the acidity of gastric juice, protect the small intestine, and provide an optimum pH for hydrolytic enzymes present in the lumen What portion of the exocrine pancreas secretes most of this bicarbonate- and sodium-rich alkaline fluid? (A) Intercalated ducts (B) Interlobular ducts (C) Intralobular ducts (D) Pancreatic duct of Santorini (E) Pancreatic duct of Wirsung 25 A group of medical students examine a virtual microscope slide of the pancreas at low magnification Identify the structure indicated by the arrow (shown in the image) 27 The virtual microscope slide described in Question 25 is examined at higher magnification Identify the structure indicated by the arrow (shown in the image) (A) Accessory pancreatic duct (B) Intercalated duct (C) Interlobular duct (D) Intralobular duct (E) Main pancreatic duct 28 A 62-year-old alcoholic presents to the emergency room with hours of severe abdominal pain and vomiting Physical examination discloses exquisite abdominal tenderness Serum levels of amylase and lipase are elevated These laboratory data indicate that this patient has suffered injury to which of the following internal organs? (A) Duodenum (B) Gallbladder (C) Liver (D) Pancreas (E) Stomach 0002076927.INDD 194 3/19/2014 3:01:38 PM Liver, Biliary System, and Pancreas 29 A 69-year-old man is brought to the emergency room in a disoriented state Physical examination reveals an odor of alcohol, as well as jaundice and ascites Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and bilirubin are all elevated Increased serum levels of alkaline phosphatase are an indicator of injury to which of the following tissues/structures? (A) Bile ducts (B) Centrilobular hepatocytes (C) Islets of Langerhans (D) Pancreatic exocrine acini (E) Periportal hepatocytes 0002076927.INDD 195 195 30 A 44-year-old woman comes to the physician with a 6-week history of episodic hunger and fainting spells She is currently seeing a psychiatrist because she is irritable and quarreling with her family Laboratory studies show a serum glucose concentration of 35 mg/dL (normal = 90 mg/dL) A CT scan of the abdomen demonstrates a 1.5-cm mass in the pancreas An EM study of the tumor reveals membrane-bound, dense-core granules These secretory vesicles most likely contain which of the following pancreatic hormones? (A) Glucagon (B) Insulin (C) Pancreatic polypeptide (D) Secretin (E) Somatostatin 3/19/2014 3:01:38 PM 196 Chapter 14 ANSWERS The answer is B: Central vein. The liver is the largest visceral organ in the body It is located in the upper right quadrant of the abdominal cavity, where it is protected by the ribcage The liver arises as a diverticulum of the embryonic foregut It receives blood from two sources: (1) hepatic artery and (2) hepatic portal vein The parenchymal cells of the liver, termed hepatocytes, form plates that are separated by sinusoidal capillaries Blood filters through the sinusoids and is drained by terminal hepatic venules to the inferior vena cava The classic liver lobule is described as a six-sided prism, with portal triads (bile duct, hepatic artery, and portal vein) located at the angles of each lobule The terminal hepatic venule (also referred to as the central vein) is located at the center of each lobule The liver is encapsulated with fibrous connective tissue (Glisson capsule) None of the other structures listed is found at the center of the classic liver lobule Keywords: Liver lobule, hepatocytes The answer is D: Portal triad. The circle shown in the image identifies a portal triad composed of a portal vein, bile duct, and hepatic artery The portal triad is held together by loose connective tissue The portal vein (choice E) is thin walled, and its diameter is much larger than that of the hepatic artery (choice C) The portal vein collects blood from the superior mesenteric and splenic veins It delivers poorly oxygenated, but nutrient-rich, blood to hepatocytes lining the sinusoids Hepatic arteries arise from the celiac trunk—an unpaired branch of the abdominal aorta Two or three layers of smooth muscle surround the hepatic artery/arteriole None of the other choices exhibit histologic features of the hepatic portal triad Keywords: Liver, portal triad The answer is E: Terminal hepatic venules. This image reveals the central veins (terminal hepatic venules) of two adjoining liver lobules (arrows, shown in the image) Hepatic sinusoids (open spaces) can be seen converging on the central veins A portal triad is visible between the veins Central veins collect blood from the hepatic sinusoids They coalesce to form sublobular veins (choice D) that drain to hepatic veins that empty into the inferior vena cava None of the other vessels are found at the center of a liver lobule Keywords: Liver, terminal hepatic venules The answer is E: Glucuronyltransferase. Hepatocyte functions can be classified as (1) metabolic (e.g., gluconeogenesis), (2) synthetic (e.g., secretion of albumin), (3) storage (e.g., iron and triglyceride storage), and (4) excretory (e.g., secretion of bile) One of the c omponents of bile is conjugated bilirubin (a bile pigment) Bilirubin is the end product of hemoglobin degradation It is poorly 0002076927.INDD 196 soluble in the blood In order to be removed from the circulation, bilirubin must be transported into hepatocytes, conjugated with glucuronic acid (to make it water soluble), and then excreted into the bile for elimination Approximately 70% of normal newborns exhibit a transient unconjugated hyperbilirubinemia This “physiological jaundice” is more pronounced in premature infants due to inadequate hepatic clearance of bilirubin related to organ immaturity Fetal bilirubin levels in utero remain low because bilirubin crosses the placenta, where it is conjugated and excreted by the mother’s liver High concentrations of unconjugated bilirubin in a neonate can cause irreversible brain injury (referred to as kernicterus) The other enzymes are unrelated to bilirubin excretion by the liver Keywords: Neonatal jaundice The answer is A: Centrilobular hepatocytes. Patients with right-sided heart failure have pitting edema of the lower extremities and an enlarged and tender liver A generalized increase in venous pressure, typically from chronic right-sided heart failure, results in an increase in the volume of blood in many organs (e.g., liver, spleen, kidneys) The liver is particularly vulnerable to chronic passive congestion because the hepatic veins empty into the vena cava immediately inferior to the heart In patients with chronic passive congestion of the liver, the central veins of the hepatic lobule become dilated Increased venous pressure leads to dilation of the sinusoids and pressure atrophy of centrilobular hepatocytes The other choices are less commonly affected by chronic passive congestion of the liver Keywords: Liver sinusoids, congestive heart failure The answer is D: Portal vein. As mentioned above, the liver has a dual blood supply: The hepatic artery provides oxygen-rich blood, whereas the portal vein provides blood that is nutrient rich, but oxygen poor Both sources of blood (arterial and venous) mix in the hepatic sinusoids Approximately 75% of the blood flowing through the liver is derived from the hepatic portal vein The other 25% of the blood supply is derived from the hepatic artery (choice B) Sublobular veins (choice E) drain to the inferior vena cava None of the other vessels provide a major source of blood to the liver Keywords: Liver, portal vein The answer is A: Fenestrations. Hepatic sinusoids are lined by a discontinuous endothelium that facilitates access of hepatocytes to the blood The endothelial cells exhibit small windows in their cytoplasm (fenestrations) Moreover, the basal lamina of the endothelium is absent over large areas, and there are gaps between adjacent cells Hepatic sinusoids are also lined by resident macrophages (referred to as Kupffer cells) Slit-pore diaphragms (choice D) connect podocyte foot processes in the renal glomerulus, but these structures are not found 3/19/2014 3:01:38 PM Liver, Biliary System, and Pancreas in the liver None of the other cytologic features characterize endothelial cells lining hepatic sinusoids Keywords: Liver sinusoids, fenestrated capillaries The answer is D: Space of Disse. Hepatocytes are separated from vascular endothelial cells and Kupffer cells by a perisinusoidal space (of Disse) This microscopic space provides a location for the exchange of fluid and biomolecules between hepatocytes and blood Microvilli on the hepatocyte basal membrane fill the space of Disse and increase the surface area available for transport (endocytosis and exocytosis) Ducts of Santorini and Wirsung (choices A and B) are found in the pancreas RokitanskyAschoff sinuses (choice C) are deep invaginations of the mucosa in the wall of the gallbladder The space of Mall (choice E) is located between hepatocytes and connective tissue of the portal triads Keywords: Liver, hepatocytes The answer is D: Hemosiderin. The liver stores most of the iron in the body Iron is carried in the blood by transferrin (choice E) Receptors on hepatocytes bind transferrin and transport iron into the cell Intracellular iron is bound by ferritin Hemosiderin is a partially denatured form of ferritin that aggregates easily and is recognized microscopically as yellow-brown granules within the cytoplasm Prussian blue is commonly used to identify iron storage pigments within cells Hereditary hemochromatosis is an abnormality of iron absorption in the small intestine In this genetic disease, iron is stored mostly in the form of hemosiderin, primarily in the liver Bilirubin (choice A) is a product of heme catabolism that may accumulate in liver cells—but does not contain iron Cytochromes are mitochondrial proteins that contain iron, but not store iron within hepatocytes Hemoglobin (choice C) is the iron-containing pigment of RBCs Keywords: Hemosiderosis, hemochromatosis 10 The answer is B: Cytochrome P450. The liver is the principal organ involved in detoxification of foreign substances, including industrial chemicals, pharmaceutical drugs, and bacterial toxins Small doses of acetaminophen (an analgesic) are absorbed from the stomach and small intestine and conjugated in the liver to form nontoxic derivatives In cases of overdose, the normal pathway of acetaminophen metabolism is saturated Excess acetaminophen is then metabolized in the liver via the mixed function oxidase (cytochrome P450) system, yielding oxidative metabolites that cause predictable hepatic necrosis These metabolites initiate lipid peroxidation, which damages the plasma membrane and leads to hepatocyte cell death The toxic dose of acetaminophen after a single acute ingestion is in the range of 150 mg/kg in children and g in adults Drug toxicity should be suspected in all cases of acute hepatitis None of the other enzymes metabolizes acetaminophen to generate reactive oxygen species Keywords: Liver, predictable necrosis 0002076927.INDD 197 197 11 The answer is A: Blood products from the spleen. This image shows a central vein surrounded by sinusoids The scattered black objects represent Kupffer cells that have picked up carbon particles from the circulation Kupffer cells belong to the mononuclear phagocytic system Their cellular processes span the hepatic sinusoids, searching for necrotic debris and foreign material to ingest Most damaged or senescent RBCs are removed from the circulation by macrophages in the spleen; however, Kupffer cells in the liver also serve this function Portal venous blood transports nutrients and toxins from the gastrointestinal tract (choices B, D, and E), as well as endocrine secretions from the pancreas (choice C); however, Kupffer cells not internalize these blood components Keywords: Kupffer cells, hepatic sinusoids 12 The answer is A: Cholangiocytes. The principal excretory product of the liver is bile Bile provides a vehicle for the elimination of cholesterol and bilirubin, and bile salts facilitate the digestion and absorption of dietary fat Hepatocytes excrete bile into small canals (canaliculi) that drain to bile ducts within the portal triads Intrahepatic and extrahepatic bile ducts are lined by cholangiocytes These cuboidal to columnar epithelial cells continuously monitor the composition and flow of bile The patient described in this clinical vignette has an autoimmune disease (primary biliary cirrhosis) that leads to chronic destruction of intrahepatic bile ducts The bile ducts are surrounded by lymphocytes (primarily CD8+ T cells) As a result of this destructive inflammatory process, the small bile ducts all but disappear None of the other cells provides a lining epithelium for the biliary tree Keywords: Primary biliary cirrhosis, cholangiocytes 13 The answer is C: Hepatic stellate cells. Vitamin A is essential for vision, healthy skin, and proper functioning of the immune system Hepatic stellate cells (commonly referred to as Ito cells) store vitamin A These mesenchymal cells are located between hepatocytes and endothelial cells in the perisinusoidal space of Disse They store vitamin A as retinyl esters and secrete retinol bound to retinol-binding protein Retinol is taken up by rods and cones in the retina to form the visual pigment, rhodopsin Another derivative of vitamin A, retinoic acid, helps regulate the differentiation of squamous epithelial cells Vitamin A deficiency causes squamous metaplasia in many tissues In the cornea, it may progress to softening of the tissue (keratomalacia) and corneal ulceration In response to liver injury (e.g., alcoholic hepatitis), hepatic stellate cells (Ito cells) differentiate into myofibroblasts that synthesize collagens Collagen synthesis by Ito cells contributes to hepatic cirrhosis in patients with endstage liver disease Keywords: Night blindness, vitamin A deficiency, hepatic stellate cells 3/19/2014 3:01:38 PM 198 Chapter 14 14 The answer is A: Bile duct. This image shows a portal triad consisting of a portal vein, bile duct, and hepatic artery The arrow points to a bile duct, and the asterisk indicates the lumen of a thin-walled, portal vein (shown in the image) The intrahepatic bile duct is lined by cholangiocytes These columnar epithelial cells are characterized by the presence of apical membrane microvilli, tight intercellular junctions, and a complete basal lamina Their nuclei are located in the basal cytoplasm, suggesting that their apical cytoplasm is specialized for absorption and/or secretion None of the other structures exhibit the distinctive histologic features of intrahepatic bile ducts Keywords: Liver, bile ducts, portal triad 15 The answer is E: Intrahepatic bile lakes. Bile canaliculi join to form canals of Herring within the liver lobule These short canals are lined by both hepatocytes and cholangiocytes Canals of Herring deliver bile to larger ducts in the biliary tree Intrahepatic ducts coalesce to form the hepatic duct, which joins the cystic duct to form the common bile duct The common bile duct joins the second part of the duodenum at the ampulla of Vater Obstruction of the canals of Herring, or the other intrahepatic bile ducts, leads to bile stasis (cholestasis) Cholestasis is characterized by the presence of bile pigment in hepatocytes and the accumulation of bile “lakes” within dilated canaliculi None of the other pathologic changes is associated with injury to the canals of Herring Keywords: Cholestasis 16 The answer is A: Cilia. Bile contains a mixture of cholesterol, conjugated bilirubin, phospholipids, cholic acids, mucins, and electrolytes Bile emulsifies dietary fats to facilitate enzymatic digestion and absorption Bile excretion is stimulated by the release of polypeptide hormones (cholecystokinin, gastrin, and motilin) from enteroendocrine cells in the duodenum Each cholangiocyte contains a primary cilium that features a basal body and a + arrangement of microtubules in the axoneme These nonmotile organelles serve as molecular sensors that continuously monitor the flow of bile Flagella (choice B) are tubulin-based organelles that provide locomotion to sperm Cholangiocytes feature hemidesmosomes (choice C) and microvilli (choice D), but these membrane structures not monitor the flow of bile Stereocilia (choice E) are long microvilli found in the epididymis and inner ear Keywords: Biliary system, cholangiocytes, cilia 17 The answer is A: Canal of Herring. The liver has a remarkable ability to regenerate in response to injury For example, in about 15% of alcoholics, hepatocellular necrosis, fibrosis, and regeneration eventually lead to the formation of fibrous septa surrounding hepatocellular nodules These are the histopathologic features of hepatic 0002076927.INDD 198 cirrhosis A variety of observational and experimental studies suggest that hepatic stem cells line the canals of Herring In response to injury, these multipotent stem cells proliferate and migrate into the liver parenchyma to restore structure and function The space of Disse (choice D) provides a location for communication between hepatocytes and blood The space of Mall (choice E) provides a location for the accumulation and transport of lymph None of the other locations are believed to harbor hepatic stem cells Keywords: Hepatic cirrhosis, alcoholic liver disease 18 The answer is B: Cholesterol. The gallbladder is located in the upper right quadrant of the abdominal cavity on the inferior (visceral) surface of the liver Risk factors for cholesterol stones include female sex, diabetes, pregnancy, and estrogen therapy Solitary, yellow, hard gallstones are associated with bile that is supersaturated with cholesterol During their reproductive years, women are up to three times more likely to develop cholesterol gallstones than men If the bile contains excess cholesterol, it becomes supersaturated and precipitates to form stones In obese women, cholesterol secretion by the liver is increased None of the other components of bile is associated with the pathogenesis of gallstones Keywords: Cholelithiasis, gallbladder 19 The answer is C: Mucosal folds. The mucosa of the gallbladder is lined by a simple columnar epithelium and a lamina propria of loose connective tissue The mucosa of the gallbladder has numerous deep folds that may appear as glands in some tissue sections (shown in the image) The lining epithelium is characterized by the presence of tight junctions, apical membrane microvilli, and lateral membrane plications (interdigitations) Approximately 20% of men and 35% of women are found to have gallstones at autopsy Most complications associated with cholelithiasis are related to obstruction of the biliary tree Stones that obstruct the common bile duct lead to obstructive jaundice, cholangitis, and acute pancreatitis Canals of Herring (choice A), hepatic ducts (choice B), and submucosal glands (choice E) are not found in the gallbladder Mucin-secreting mucosal glands may be seen in the neck of the gallbladder; however, the epithelial structures identified in this image are not composed of mucous cells Keywords: Cholelithiasis, gallbladder 20 The answer is E: Submucosa. The wall of the gallbladder is unusual in that it does not feature a muscularis mucosae or submucosa External to the lamina propria (choice B) is the muscularis externa (choice C) This layer is composed of randomly oriented smooth muscle fibers Contraction of the smooth muscle forces bile through the cystic duct and down the common bile duct to the duodenum Because the gallbladder attaches to 3/19/2014 3:01:38 PM Liver, Biliary System, and Pancreas the inferior surface of the liver, it features both an adventitia and a serosa (choices A and D) Keywords: Gallbladder 21 The answer is A: Aquaporin. The concentration of bile within the lumen of the gallbladder depends on active and passive transport Na/K ATPase in the lateral membrane domain of epithelial cells pumps sodium from the cytoplasm to the lamina propria This energy-dependent process creates a gradient of electrolytes that draws water from the lumen of the gallbladder, through the epithelium, to the lamina propria, for removal by vascular and lymphatic channels This active transport mechanism is supplemented by passive transport of water through special membrane pores These water channels are composed of integral membrane proteins, termed aquaporins Cadherins and occludins (choices B and C) are cell adhesion molecules Perforin (choice D) is a cytotoxic protein that is secreted by killer T lymphocytes Porins (choice E) form channels in the outer membranes of bacteria Keywords: Aquaporins, gallbladder 22 The answer is C: Pancreas. The pancreas is a retroperitoneal organ situated between the second part of the duodenum and the spleen The pancreas is composed of both exocrine and endocrine glandular tissues Lobules of the exocrine pancreas are separated by connective tissue septa Endocrine cells in the pancreas are organized as compact microglands, referred to as islets of Langerhans The image shows four spherical islets surrounded by acini of the exocrine pancreas The pancreas contains millions of islets, primarily in the tail of the pancreas Functional cell types in the islets of Langerhans include alpha (α), beta (β), and delta (δ) cells Each cell type produces a different polypeptide hormone (e.g., insulin, glucagon, or somatostatin) None of the other organs feature islets of Langerhans Keywords: Pancreas, islets of Langerhans 23 The answer is E: Serous. The secretory units of the exocrine pancreas are small berry-shaped structures (acini) that are lined by a simple epithelium of enzyme-secreting serous cells These epithelial cells store zymogen granules in their apical cytoplasm and secrete digestive enzymes that are activated within the lumen of the duodenum The eosinophilia of pancreatic acinar cells reflects stores of zymogen granules in their apical cytoplasm The cells are pyramidal in shape, with a broad basal membrane and a narrow apical membrane that surrounds an intercalated duct Endocrine cells in the pancreas (choice A) are found in the islets of Langerhans Goblet cells (choice B) are unicellular glands found in the respiratory tree and gastrointestinal tract Mucous cells are filled with heavily glycosylated proteins that not stain with H&E Paracrine cells (choice D) signal to neighboring cells Keywords: Pancreas, exocrine glands 0002076927.INDD 199 199 24 The answer is A: Intercalated ducts. Exocrine secretions of the pancreas drain through ducts of various sizes to reach the main pancreatic duct of Wirsung (choice E) or the accessory pancreatic duct of Santorini (choice D) The acinar cells release digestive enzymes into intercalated ducts that originate within the secretory unit Centroacinar cells line the proximal portion of these small ducts Intercalated ducts join to form intralobular (choice C) ducts that coalesce to form larger interlobular (choice B) ducts Proenzymes secreted by the acinar cells are diluted with an alkaline pH fluid that is produced primarily by epithelial cells lining the intercalated ducts Submucosal (Brunner) glands in the proximal part of the duodenum also secrete an alkaline fluid that helps to neutralize the acidity of gastric juice The other pancreatic ducts not contribute as much fluid as intercalated ducts Keywords: Pancreas, intercalated ducts 25 The answer is B: Interlobular duct. The arrow identifies a large pancreatic duct surrounded by dense irregular connective tissue This duct is best described as an interlobular duct, because it is located in connective tissue septa between pancreatic lobules Interlobular ducts are lined by low columnar epithelium, whereas intralobular ducts are lined by cuboidal epithelium Intercalated ducts (choice A) drain pancreatic acini Intralobular ducts (choice C) are located within pancreatic lobules The duct indicated in the image is not large enough to be the main pancreatic duct (choice D) Rokitansky-Aschoff sinuses (choice E) are found in the wall of the gallbladder None of the other structures exhibit the morphologic features of a pancreatic interlobular duct Keywords: Pancreas, exocrine ducts 26 The answer is E: Trypsin. The pancreas secretes about L of fluid per day (about the same volume as the gallbladder) Digestive proenzymes secreted by the pancreas are activated when they reach the lumen of the duodenum Activation is a two-step process First, enteropeptidase in the glycocalyx of the intestinal brush border cleaves pancreatic trypsinogen to form trypsin (a serine protease) Second, trypsin cleaves other pancreatic proenzymes to yield active enzymes for the digestion of food None of the other enzymes activates pancreatic proenzymes within the lumen of the duodenum Keywords: Pancreas, trypsin 27 The answer is D: Intralobular duct. This image shows a particularly large intralobular duct that is surrounded by dense irregular connective tissue The duct is located entirely within a pancreatic lobule The smallest intralobular ducts are about the same diameter as an acinus These ducts become progressively larger as they coalesce to form interlobular ducts None of the other pancreatic ducts exhibit the distinct histologic features of an intralobular duct Keywords: Pancreas, exocrine ducts 3/19/2014 3:01:38 PM 334 Chapter 21 Villous and tubular elements are observed in this polyp Microscopic examination of the stalk further reveals a focus of mucus-producing adenocarcinoma (malignant neoplasm capable of invasion and metastasis) As long as dysplastic foci remain confined to the polyp mucosa, these lesions are almost always cured by surgical resection None of the other choices describe the histopathology of an adenomatous polyp of the colon Keywords: Adenocarcinoma of the colon, adenomatous polyp of the colon 33 The answer is C: There is expansion of the mesangium- forming nodular lesions. The patient’s renal biopsy reveals a prominent increase in the mesangial matrix, forming several nodular lesions These microscopic findings are seen in patients with diabetic glomerulosclerosis PAS reagent stains complex carbohydrates that are conjugated extracellular matrix proteins via nonenzymatic glycosylation—a reaction that occurs at an accelerated rate in diabetics with hyperglycemia Diabetes mellitus, a complex metabolic disease associated with glucosuria and polyuria, is the leading cause of end-stage renal disease in the United States, accounting for a third of all patients with chronic renal failure In patients with diabetic glomerulosclerosis, the renal glomeruli show diffuse mesangial matrix expansion with focal, segmental, and nodular lesions Diabetic glomerulosclerosis eventually results in progressive renal failure None of the other choices describe histopathologic findings evident in this biopsy specimen Keywords: Diabetic nephropathy, diabetes mellitus 34 The answer is A: The cell type of the epithelium has been changed. The patient’s bladder biopsy shows squamous metaplasia of the urothelium In this patient, parasitic infestation of the bladder caused the normal transitional cell epithelium to be replaced by a protective, stratified squamous epithelium Squamous cell carcinoma of the bladder can develop in foci of squamous metaplasia, and a high incidence of bladder cancer is found in countries with endemic schistosomiasis The other choices not reflect squamous metaplasia of the bladder mucosa Keywords: Squamous cell carcinoma of the bladder 35 The answer is C: There is a proliferation of abnormal germ cells. The patient’s testis shows no signs of spermatogenesis (i.e., no signs of haploid male germ cells) but does show large, atypical cells within the seminiferous epithelium Recent studies indicate that these large cells are triploid These atypical cells are confined within the tubular basement membrane and represent an example of carcinoma in situ Half of men with intratubular germ cell neoplasia will develop invasive cancer (e.g., seminoma or embryonal carcinoma) within years Nuclear transcription factors OCT3 and OCT4 are reliable markers for these atypical germ cells None of the other choices 0002076934.INDD 334 describe the histopathologic findings evident in this patient’s testicular biopsy Keywords: Seminoma, testicular cancer 36 The answer is E: Proliferation of epithelial cells. The prostate needle biopsy shows new uncontrolled proliferation of the glandular epithelium (adenocarcinoma) In 1990, prostatic adenocarcinoma became the cancer most frequently diagnosed in American men, surpassing the incidence of lung cancer for the first time It is generally accepted that prostatic intraepithelial neoplasia lesions progress to invasive prostatic adenocarcinoma There is no evidence that prostatic adenocarcinoma originates from hyperplastic nodules seen in patients with nodular prostatic hyperplasia Prostatic adenocarcinomas are commonly multicentric and located in peripheral zones of the prostate gland None of the other choices describe the histopathology of prostate cancer Keywords: Prostate cancer, adenocarcinoma of the prostate 37 The answer is D: Perinuclear halos. Compared to normal cervical epithelial cells (image on left), the patient’s Pap smear (image on right) reveals atypical cells with enlarged nuclei and prominent perinuclear clear spaces These atypical cells are referred to as koilocytes For this Pap smear, the cytology report will note cervical squamous cells with “koilocytotic atypia.” Human papillomavirus (HPV) is a DNA virus that infects a variety of skin and mucosal surfaces to produce wart-like lesions (verrucae and condylomata) In the female reproductive tract, HPV infections are linked to the pathogenesis of cervical cancer The morphologic hallmark of HPV infection is koilocytotic atypia, a term that denotes the presence of sharply demarcated, large perinuclear halos, combined with alterations in the chromatin pattern of squamous epithelial cells These perinuclear halos are filled with replicating virus HPV particles Lewy bodies (choice A) are intracellular aggregates of synuclein protein found in dopaminergic neurons of patient’s with Parkinson disease Nuclear pyknosis (choice B) is hallmark of cell death, in which nuclear chromatin undergoes irreversible clumping and condensation The normal Pap smear shows two cells with pyknotic nuclei (arrows) The patient’s Pap smear does not show cellular aggregates with papillary morphology (choice C) Endocervical cells may undergo squamous metaplasia (choice E), but Pap smears taken from the ectocervix of the adult typically show squamous cell morphology Keywords: Cervix, Pap smear, human papillomavirus 38 The answer is C: There is enlargement and growth of follicular cells. This thyroid biopsy reveals active follicles lined by hyperplastic, tall columnar epithelial cells The colloid appears scalloped at the periphery of the follicle Scalloping represents active uptake of 3/19/2014 3:22:01 PM Introduction to Histopathology thyroglobulin for processing and transport to the systemic circulation Inactive thyroid follicles are typically lined by a low cuboidal epithelium (image on left) These clinicopathologic findings are consistent with hyperthyroidism Graves disease is the most frequent cause of hyperthyroidism in young adults It is an autoimmune disorder characterized by diffuse goiter, hyperthyroidism, and exophthalmos Patients with Graves disease are hyperthyroid due to the presence of stimulating IgG antibodies that bind to the TSH receptor expressed on the plasma membrane of follicular cells Patients note the gradual onset of nonspecific symptoms, such as nervousness, emotional lability, tremor, weakness, and weight loss They are intolerant of heat, seek cooler environments, tend to sweat profusely, and may report heart palpitations None of the other choices describe histopathologic features of hyperthyroidism Keywords: Graves disease, hyperthyroidism 39 The answer is B: Carcinoma in situ. The patient’s breast biopsy reveals intraductal carcinoma in situ (DCIS), which arises in the terminal duct lobular unit, greatly distorting the ducts by its growth (image on right) DCIS carries a 20% to 30% risk of developing invasive carcinoma in the same breast over the ensuing 20 years Atypical ductal hyperplasia (choice A) is a 0002076934.INDD 335 335 component of benign, fibrocystic change of the breast Intraductal papilloma (choice C) is a benign tumor that usually arises in a terminal lactiferous duct and causes nipple discharge Examination of this patient’s breast biopsy at low magnification does not reveal evidence of tumor cells within either blood or lymphatic vessels (choice D) nor does it reveal tumor cells leaving ducts and invading the adjacent stromal connective tissue (choice E) Keywords: Breast cancer, intraductal carcinoma in situ 40 The answer is E: There is increased cellularity of the gland. This thyroid biopsy reveals increased cellularity, with monomorphic cells forming small follicular structures filled with colloid A single, well-circumscribed, thyroid nodule in a young patient most likely represents a follicular adenoma—a benign neoplasm that exhibits follicular differentiation It is the most common tumor of the thyroid and typically presents in euthyroid persons as a solitary “cold” nodule (i.e., a tumor that does not take up radiolabeled iodine) Follicular adenoma is an encapsulated neoplasm in which the cells are arranged in follicles that resemble normal thyroid tissue None of the other choices describe histopathologic features of thyroid neoplasia Keywords: Follicular adenoma of the thyroid 3/19/2014 3:22:01 PM Appendix A Normal Reference Range* Laboratory Test Reference Range Clinical Chemistry Tests (Serum) Alanine aminotransferase (ALT) Male 1–45 IU/L @ 37°C Female 1–30 IU/L @ 37°C Albumin 40–400 IU/L @ 37°C 30–160 IU/L @ 37°C Alpha-1-antitrypsin, total 96–199 mg/dL Ammonia 11–35 μmol/L Amylase