Robbins and Cotran Review: Cell Injury Flashcards
1 A 17-year-old boy infected with hepatitis A experiences mild nausea for about 1 week and develops very mild scleral icterus. On physical examination, he has minimal right upper quadrant tenderness. Laboratory findings include a serum AST of 68 U/L, ALT of 75 U/L, and total bilirubin of 5.1 mg/dL. The increase in this patient's serum enzyme levels most likely results from which of the following changes in the hepatocytes? □ (A) Autophagy by lysosomes □ (B) Clumping of nuclear chromatin □ (C) Defects in the cell membrane □ (D) Dispersion of ribosomes □ (E) Swelling of the mitochondria
1 (C) Irreversible cell injury is associated with loss of membrane integrity. This allows intracellular enzymes to leak into the serum. All other morphologic changes listed are associated with reversible cell injury, in which the cell membrane remains
intact.
2 A 16-year-old boy sustained blunt trauma to the abdomen when the vehicle he was driving struck a bridge abutment at high speed. Peritoneal lavage shows a hemoperitoneum, and at laparotomy, a small portion of the left lobe of the liver is removed because of the injury. Several weeks later, a CT scan of the abdomen shows that the liver has nearly regained its size before the injury. Which of the following processes best explains this CT scan finding? □ (A) Apoptosis □ (B) Dysplasia □ (C) Fatty change □ (D) Hydropic change □ (E) Hyperplasia □ (F) Hypertrophy □ (G) Metaplasia
2 (E) The liver is one of the few organs in the human body that can partially regenerate. This is a form of compensatoryhyperplasia. The stimuli to hepatocyte mitotic activity cease when the liver has attained its normal size. Apoptosis is singlecell death and frequently occurs with viral hepatitis. Dysplasia is disordered epithelial cell growth that can be premalignant.Fatty change can lead to hepatomegaly; this is not a degenerative process, but is the result of toxic hepatocyte injury.Hydropic change, or cell swelling, does not produce regeneration. Hepatocytes can reenter the cell cycle and proliferate toregenerate the liver; they do not just increase in size.
3 On a routine visit to the physician, an otherwise healthy 51-year-old man has a blood pressure of 150/95 mm Hg. If his hypertension remains untreated for years, which of the following cellular alterations would most likely be seen in his myocardium? □ (A) Atrophy □ (B) Hyperplasia □ (C) Metaplasia □ (D) Hemosiderosis □ (E) Hypertrophy
3 (E) The pressure load on the left ventricle results in an increase in myofilaments in the existing myofibers. The result ofcontinued stress from hypertension is eventual heart failure with decreased contractility, but the cells do not decrease insize. Metaplasia of muscle does not occur, although loss of muscle occurs with aging as myofibers are replaced by fibroustissue and adipose tissue. Hemosiderin deposition in the heart is a pathologic process resulting from increased iron storesin the body.
4 A 72-year-old man died suddenly from congestive heart failure. At autopsy, the heart weighed 580 g and showed marked
left ventricular hypertrophy and minimal coronary arterial atherosclerosis. A serum chemistry panel ordered before death
showed no abnormalities. Which of the following pathologic processes best accounts for the appearance of the aortic
valve seen in the figure?
□ (A) Amyloidosis
□ (B) Dystrophic calcification
□ (C) Lipofuscin deposition
□ (D) Hemosiderosis
□ (E) Fatty change
4 (B) The valve is stenotic because of nodular deposits of calcium. The process is “dystrophic” because calcium
deposition occurs in damaged tissues. The damage in this patient is a result of the wear and tear of aging. Amyloid
deposition in the heart typically occurs within the myocardium and the vessels. The amount of lipofuscin increases within myocardial fibers (not valves) with aging. Hereditary hemochromatosis is a genetic defect in iron absorption that results in extensive myocardial iron deposition (hemosiderosis). Fatty change is uncommonly seen in myocardium, but infiltration offat cells between myofibers can occur.
5 A 69-year-old woman has had transient ischemic attacks for the past 3 months. On physical examination, she has an
audible bruit on auscultation of the neck. A right carotid endarterectomy is performed. The curetted atheromatous plaque
has a grossly yellow-tan, firm appearance. Microscopically, which of the following materials can be found in abundance in
the form of crystals that produce long, cleft-like spaces?
□ (A) Glycogen
□ (B) Lipofuscin
□ (C) Hemosiderin
□ (D) Immunoglobulin
□ (E) Cholesterol
5 (E) Cholesterol is a form of lipid commonly deposited within atheromas in arterial walls, imparting a yellow color to these
plaques. Glycogen is a storage form of carbohydrate seen mainly in liver and muscle. Lipofuscin is a brown pigment that increases with aging in cell cytoplasm, mainly in cardiac myocytes and in hepatocytes. Hemosiderin is a storage form ofiron that appears in tissues of the mononuclear phagocyte system (e.g., marrow, liver, spleen), but can be widelydeposited with hereditary hemochromatosis. Immunoglobulin occasionally may be seen as rounded globules in plasma cells (i.e., Russell bodies).
6 A 38-year-old woman experienced severe abdominal pain with hypotension and shock that led to her death within 36 hours after the onset of the pain. From the gross appearance of the mesentery, seen in the figure at the bottom of theprevious column, which of the following events has most likely occurred? □ (A) Hepatitis B virus infection □ (B) Small intestinal infarction □ (C) Tuberculous lymphadenitis □ (D) Gangrenous cholecystitis □ (E) Acute pancreatitis
6 (E) The focal, chalky white deposits are areas of fat necrosis resulting from the release of pancreatic lipases in a patientwith acute pancreatitis. Viral hepatitis does not cause necrosis in other organs, and hepatocyte necrosis from viral infections occurs mainly by means of apoptosis. Intestinal infarction is a form of coagulative necrosis. Tuberculosis produces caseous necrosis. Gangrenous necrosis is mainly coagulative necrosis, but occurs over an extensive area.
7 In an experiment, cells are subjected to radiant energy in the form of x-rays. This results in cell injury caused by hydrolysis of water. Which of the following cellular enzymes protects the cells from this type of injury? □ (A) Phospholipase □ (A) Phospholipase □ (B) Glutathione peroxidase □ (C) Endonuclease □ (D) Lactate dehydrogenase □ (E) Protease
7 (B) Intracellular mechanisms exist that deal with free radical generation, as can occur with radiant injury from irradiation.Glutathione peroxidase reduces such injury by catalyzing the breakdown of hydrogen peroxide. Phospholipases decrease cellular phospholipids and promote cell membrane injury. Proteases can damage cell membranes and cytoskeletal proteins. Endonucleases damage nuclear chromatin. Lactate dehydrogenase is present in a variety of cells, and its elevation in the serum is an indicator of cell death.
8 A 47-year-old woman has had worsening dyspnea for the past 5 years. A chest CT scan shows panlobular emphysema. Laboratory studies show the PiZZ genotype of α1-antitrypsin (AAT) deficiency. A liver biopsy specimen examined microscopically shows abundant PAS-positive globules within periportal hepatocytes. Which of the following molecular mechanisms is most likely responsible for this finding in the hepatocytes?
□ (A) Excessive hepatic synthesis of AAT
□ (B) Retention of poorly folded AAT in the endoplasmic reticulum
□ (C) Decreased catabolism of AAT in lysosomes
□ (D) Inability to metabolize AAT
□ (E) Impaired dissociation of AAT from chaperones
8 (B) Mutations in the AAT gene give rise to AAT molecules that cannot fold properly. In the PiZZ genotype, both alleles have the mutation. The partially folded molecules accumulate in the endoplasmic reticulum and cannot be secreted. Impaired dissociation of the CFTR protein from chaperones causes many cases of cystic fibrosis. There is no abnormality in the synthesis, catabolism, or metabolism of AAT in patients with AAT deficiency.
9 A 68-year-old woman suddenly lost consciousness; on awakening 1 hour later, she could not speak or move her right arm and leg. Two months later, a head CT scan showed a large cystic area in the left parietal lobe. Which of the following pathologic processes has most likely occurred in the brain? □ (A) Fat necrosis □ (B) Coagulative necrosis □ (C) Apoptosis □ (D) Liquefactive necrosis □ (E) Karyolysis
9 (D) The high lipid content of central nervous system tissues results in liquefactive necrosis as a onsequence of ischemic injury, as in this case of a “stroke.” Fat necrosis is seen in breast and pancreatic tissues. Coagulative necrosis is the typical result of ischemia in most solid organs. Apoptosis affects single cells and typically is not grossly visible. Karyolysis refers to fading away of cell nuclei in dead cells.
10 A 30-year-old man sustains a left femoral fracture in a skiing accident, and his leg is placed in a plaster cast. After the leg has been immobilized for several weeks, the diameter of the left calf has decreased. This change is most likely to result from which of the following alterations in the calf muscles? □ (A) Aplasia □ (B) Hypoplasia □ (C) Atrophy □ (D) Dystrophy □ (E) Hyalinosis
1 0 (C) Reduced workload causes shrinkage of cell size because of loss of cell substance, a process called atrophy. Aplasia refers to lack of embryonic development; hypoplasia describes poor or subnormal development. Dystrophy of muscles refers to inherited disorders of skeletal muscles that lead to muscle weakness and wasting. Hyaline change (hyalinosis) refers to a nonspecific, pink, glassy eosinophilic appearance of cells.
11 An experiment analyzes cells for enzyme activity associated with sustained cellular proliferation. Which of the following cells is most likely to have the highest telomerase activity? □ (A) Endothelial cells □ (B) Germ cells □ (C) Neurons □ (D) Neutrophils □ (E) Erythrocytes
11 (B) Germ cells have the highest telomerase activity, and the telomere length can be stabilized in these cells. This allows testicular germ cells to retain the ability to divide throughout life. Normal somatic cells have no telomerase activity, and telomeres progressively shorten with each cell division until growth arrest occurs.
12 A 32-year-old man experiences “heartburn” and gastric reflux after eating a large meal. After many months of symptoms, he undergoes upper gastrointestinal endoscopy, and a biopsy specimen of the esophageal epithelium is obtained. Which of the following pathologic changes, seen in the figure, has most likely occurred? □ (A) Squamous metaplasia □ (B) Mucosal hypertrophy □ (C) Columnar epithelial metaplasia □ (D) Atrophy of lamina propria □ (E) Goblet cell hyperplasia
12 (C) Inflammation from reflux of gastric acid has resulted in replacement of normal esophageal squamous epithelium by intestinal-type columnar epithelium with goblet cells. Such conversion of one adult cell type to another cell type is called metaplasia. The cells are not significantly increased in size (hypertrophic). The lamina prop
13 On day 28 of her menstrual cycle, a 23-year-old woman experiences onset of menstrual bleeding that lasts for 6 days. She has had regular cycles for many years. Which of the following processes is most likely occurring in the endometrium just before the onset of bleeding? □ (A) Apoptosis □ (B) Caseous necrosis □ (C) Heterophagocytosis □ (D) Atrophy □ (E) Liquefactive necrosis
13 (A) The onset of menstruation is an example of orderly, programmed cell death (apoptosis) through hormonal stimuli. The endometrium breaks down, sloughs off, and then regenerates. Caseous necrosis is typical of granulomatous inflammation, resulting most commonly from mycobacterial infection. Heterophagocytosis is typified by the clearing of an area of necrosis through macrophage ingestion of the necrotic cells. With cellular atrophy, there is often no visible necrosis, but the tissues shrink, something that occurs in the endometrium after menopause. Liquefactive necrosis can occur in any tissue after acute bacterial infection or in the brain after ischemia.
14 In a clinical trial, a chemotherapeutic agent is given to patients with breast cancer metastases. Samples of the cancer cells are obtained and assessed for the presence of death of tumor cells by apoptosis. Mutational inactivation of which of the following products is most likely to render tumor cells resistant to the effects of such an agent? □ (A) BCL-2 □ (B) p53 □ (C) NF-κB □ (D) Cytochrome P-450 □ (E) Granzyme B
14 (B) When DNA damage is induced by chemotherapeutic drugs (or other agents), normal p53 genes trigger the cells to undergo apoptosis. When p53 is inactivated, this pathway of cell death can be blocked, rendering the chemotherapy less effective. BCL-2 and NF-κB activity favor cell survival. Cytochrome P-450 does not affect apoptosis. Granzyme B can trigger apoptosis, but it is found in cytotoxic T cells and not in tumor cells.
15 After the birth of her first child, a 19-year-old woman breastfed the infant for about 1 year. Which of the following processes that occurred in the breast during pregnancy allowed her to breastfeed the infant? □ (A) Stromal hypertrophy □ (B) Lobular hyperplasia □ (C) Epithelial dysplasia □ (D) Intracellular accumulation of fat □ (E) Ductal epithelial metaplasia
1 5 (B) Lobules increase under hormonal influence (mainly progesterone) to provide for normal lactation. The breast stroma plays no role in lactation and may increase with pathologic processes. Epithelial dysplasia denotes disordered growth and maturation of epithelial cells that may progress to cancer. Accumulation of fat within cells is a common manifestation of sublethal cell injury or, uncommonly, of inborn errors in fat metabolism. Epithelial metaplasia in the breast is a pathologic process.
16 A 22-year-old woman has a congenital anemia that has required multiple transfusions of RBCs for many years. On physical examination, she now has no significant findings; however, liver function tests show reduced serum albumin. Which of the following findings would most likely appear in a liver biopsy specimen? □ (A) Steatosis in hepatocytes □ (B) Bilirubin in canaliculi □ (C) Glycogen in hepatocytes □ (D) Amyloid in portal triads □ (E) Hemosiderin in hepatocytes
16 (E) Each unit of blood contains about 250 mg of iron. The body has no mechanism for getting rid of excess iron. About 10 to 20 mg of iron per day is lost with normal desquamation of epithelia; menstruating women lose slightly more. Any excess iron becomes storage iron, or hemosiderin. Over time, hemosiderosis involves more and more tissues of the body,
particularly the liver. Initially, hemosiderin deposits are found in Kupffer cells and other mononuclear phagocytes in the bone marrow, spleen, and lymph nodes. With great excess of iron, liver cells also accumulate iron. Steatosis usually
occurs with ingestion of hepatotoxins, such as alcohol. Bilirubin, a breakdown product of blood, can be excreted in the bile
so that a person does not become jaundiced. Glycogen storage diseases are inherited and present in childhood. Amyloid
is an abnormal protein derived from a variety of precursors, such as immunoglobulin light chains.
17 A 50-year-old man experienced an episode of chest pain 6 hours before his death. A histologic section of left ventricular myocardium taken at autopsy showed a deeply eosinophilic-staining area with loss of nuclei and cross-striations in myocardial fibers. There was no hemorrhage or inflammation. Which of the following conditions most likely produced these
myocardial changes?
□ (A) Viral infection
□ (B) Coronary artery thrombosis
□ (C) Blunt chest trauma
□ (D) Antibodies directed against myocardium
□ (E) Protein-deficient diet
17 (B) The deep eosinophilic staining, loss of nuclei, and loss of cell structure suggest an early ischemic injury, resulting in coagulative necrosis. This finding is typically caused by loss of blood flow. Viral infection could cause necrosis of the myocardium, but this is usually accompanied by an inflammatory infiltrate consisting of lymphocytes and macrophages. Blunt trauma produces hemorrhage. An immunological injury may produce focal cell injury, but not widespread ischemic injury. Lack of protein leads to a catabolic state with gradual decrease in cell size, but it does not cause ischemic changes.
18 A 69-year-old man has had difficulty with urination, including hesitancy and frequency, for the past 5 years. A digital rectal examination reveals that the prostate gland is palpably enlarged to about twice normal size. A transurethral resection of the prostate is performed, and the microscopic appearance of the prostate “chips” obtained is that of nodules of glands with intervening stroma. Which of the following pathologic processes has most likely occurred in the prostate? □ (A) Apoptosis □ (B) Dysplasia □ (C) Fatty change □ (D) Hyperplasia □ (E) Hypertrophy □ (F) Metaplasia
18 (D) Nodular prostatic hyperplasia (also known as benign prostatic hyperplasia [BPH]) is a common condition in older men that results from proliferation of prostatic glands and stroma. The prostate becomes more sensitive to androgenic stimulation with age. This is an example of pathologic hyperplasia. Apoptosis results in a loss of, not an increase in, cells. Dysplasia refers to disordered epithelial cell growth and saturation. Fatty change in hepatocytes may produce hepatomegaly. Although BPH is often called “benign prostatic hypertrophy,” this term is technically incorrect; it is the
number of glands and stromal cells that is increased, rather than the size of existing cells. A change in the glandular
epithelium to squamous epithelium would be an example of metaplasia.
19 A 54-year-old man experienced onset of severe substernal chest pain over 3 hours. An ECG showed changes consistent with an acute myocardial infarction. After thrombolytic therapy with tissue plasminogen activator (t-PA), his serum creatine kinase (CK) level increased. Which of the following events most likely occurred after t-PA therapy? □ (A) Reperfusion injury □ (B) Cellular regeneration □ (C) Chemical injury □ (D) Increased synthesis of CK □ (E) Myofiber atrophy
19 (A) If the existing cell damage is not great after myocardial infarction, the restoration of blood flow can help prevent further damage. The reperfusion of damaged cells results in generation of oxygen-derived free radicals, however, causing a reperfusion injury. The elevation in the CK level is indicative of myocardial cell necrosis because this intracellular enzyme does not leak in large quantities from intact cells. Myocardial fibers do not regenerate to a significant degree, and atrophic fibers would have less enzyme to release. t-PA does not produce a chemical injury; it induces thrombolysis to restore blood flow in blocked coronary arteries.
20 A 33-year-old woman has had increasing lethargy and decreased urine output for the past week. Laboratory studies show serum creatinine level of 4.3 mg/dL and urea nitrogen level of 40 mg/dL. A renal biopsy is performed, and the specimen is examined using electron microscopy. Which of the following morphologic changes most likely suggests a
Robbins & Cotran Review of Pathology Pg. 5diagnosis of acute tubular necrosis?
□ (A) Mitochondrial swelling
□ (B) Plasma membrane blebs
□ (C) Chromatin clumping
□ (D) Nuclear fragmentation
□ (E) Ribosomal disaggregation
20 (D) Loss of the nucleus results in cell death. All other cellular morphologic changes listed represent reversible cellular injury. The plasma membrane and intracellular organelles remain functional unless severe damage causes loss of membrane integrity.
21 A 40-year-old man had undifferentiated carcinoma of the lung. Despite chemotherapy, the man died of widespread metastases. At autopsy, tumors were found in many organs. Histologic examination showed many foci in which individual tumor cells appeared shrunken and deeply eosinophilic. Their nuclei exhibited condensed aggregates of chromatin under
the nuclear membrane. The process affecting these shrunken tumor cells was most likely triggered by the release of which of the following substances into the cytosol?
□ (A) Lipofuscin
□ (B) Cytochrome c
□ (C) Catalase
□ (D) Phospholipase
□ (E) BCL-2
21 (B) This histologic picture is typical of apoptosis produced by chemotherapeutic agents. The release of cytochrome from the mitochondria is a key step in many forms of apoptosis, and it leads to the activation of caspases. BCL-2 is an antiapoptotic protein that prevents cytochrome c release and prevents caspase activation. Lipofuscin is a pigmented residue representing undigested cellular organelles in autophagic vacuoles. Catalase is a scavenger of hydrogen peroxide. Phospholipases are activated during necrosis and cause cell membrane damage.
22 A 70-year-old man died suddenly. At autopsy, multiple tissue sites were sampled for microscopic analysis. Examination of the tissues showed noncrystalline amorphous deposits of calcium salts in gastric mucosa, renal interstitium, and alveolar walls of lungs. Which of the following conditions would most likely explain these findings? □ (A) Chronic hepatitis □ (B) Chronic glomerulonephritis □ (C) Disseminated tuberculosis □ (D) Generalized atherosclerosis □ (E) Normal aging process □ (F) Pulmonary emphysema
B
23 A 63-year-old man has a 2-year history of worsening congestive heart failure. An echocardiogram shows mitral stenosis with left atrial dilation. A thrombus is present in the left atrium. One month later, he experiences left flank pain and notes hematuria. Laboratory testing shows elevated serum AST. Which of the following patterns of tissue injury is most likely to be present? □ (A) Liquefactive necrosis □ (B) Caseous necrosis □ (C) Coagulative necrosis □ (D) Fat necrosis □ (E) Gangrenous necrosis
23 (C) Embolization of the thrombus led to blockage of a renal arterial branch, causing an acute renal infarction in this patient. An ischemic injury to most internal organs produces a pattern of cell death called coagulative necrosis. Liquefactive necrosis occurs after ischemic injury to the brain and is the pattern seen with abscess formation. Caseous necrosis can be seen in various forms of granulomatous inflammation, typified by tuberculosis. Fat necrosis is usually seen in pancreatic and breast tissue. Gangrenous necrosis is a form of coagulative necrosis that usually results from ischemia
and affects limbs.
24 At autopsy, a 40-year-old man has an enlarged (2200 g) liver with a yellow cut surface. The microscopic appearance of this liver is shown in the figure. Before death, the man's total serum cholesterol and triglyceride levels were normal, but he had a decreased serum albumin concentration and increased prothrombin time. Which of the following activities most likely led to these findings? □ (A) Injecting heroin □ (B) Playing basketball □ (C) Drinking beer □ (D) Smoking cigarettes □ (E) Ingesting aspirin
24 (C) The appearance of lipid vacuoles in many of the hepatocytes is characteristic of fatty change (steatosis) of the liver. Abnormalities in lipoprotein metabolism can lead to steatosis. Alcohol is a hepatotoxin that produces hepatic steatosis. Decreased serum albumin levels and increased prothrombin time suggest alcohol-induced hepatocyte damage. Substance abuse with heroin produces few organ-specific pathologic findings. Exercise has little direct effect on hepatic function. Smoking directly damages lung tissue, but has no direct effect on the liver. Aspirin has a significant effect on
platelet function, but not on hepatocytes.
