Question 1

A 38-year-old woman comes to the office due to jaundice, nausea, and abdominal discomfort.  Vital signs are within normal limits.  Scleral icterus and hepatomegaly are present.  Laboratory results are as follows:  Anti-smooth muscle antibody titers are elevated.  Which of the following histologic findings is most likely to be seen on biopsy of this patient's liver?

Accepted Answer

This patient with jaundice, hepatomegaly, elevated transaminases, and high anti-smooth muscle antibody titers most likely has autoimmune hepatitis (AIH). AIH occurs most commonly in women with other autoimmune conditions (eg, type 1 diabetes mellitus). It is often asymptomatic but may present with fatigue, weight loss, nausea, and/or signs of acute hepatitis (eg, jaundice, abdominal discomfort). Characteristic laboratory abnormalities include a hepatocellular pattern of liver injury (ie, predominant transaminase elevation with normal alkaline phosphatase and variable bilirubin) and the formation of a variety of autoantibodies, particularly anti-smooth muscle, which is highly specific for AIH. Hypergammaglobulinemia is also typical. The pathogenesis of AIH is incompletely understood but likely involves exposure to an environmental trigger in genetically predisposed patients, leading to regulatory T-cell dysfunction. It ultimately results in loss of self-tolerance, with an immune response against hepatic antigens. This is demonstrated histologically by lymphocyte and plasma cell infiltration of portal and periportal regions of the liver. (Choice A) Chronic hepatitis B is characterized histologically by ground-glass hepatocytes, which result from the accumulation of hepatitis B surface antigen within their cytoplasm, as well as central balloon degeneration, which reflects hepatocytes undergoing apoptosis. (Choice B) Hepatic steatosis (ie, lipid accumulation in the cytoplasm of hepatocytes) and ballooning degeneration most commonly occur in alcohol-induced hepatitis and nonalcoholic fatty liver disease. Elevated anti-smooth muscle antibody titers do not occur. (Choice C) Acetaminophen overdose can lead to hepatic inflammation and necrosis with neutrophilic infiltration (unlike AIH, which is characterized by lymphoplasmocytic infiltrates). Patients often have vomiting, diaphoresis, and confusion. (Choice D) Primary sclerosing cholangitis causes periductal fibrosis and luminal obliteration of the biliary ducts, which can lead to cholestasis. High alkaline phosphatase levels and near-normal aminotransferases are expected. Educational objective: Autoimmune hepatitis results from an immune response against hepatic antigens, leading to a lymphoplasmacytic infiltrate in the portal and periportal regions of the liver. Manifestations include fatigue, weight loss, nausea, and/or signs of acute hepatitis (eg, jaundice, abdominal discomfort). Characteristic laboratory abnormalities include a hepatocellular pattern of liver injury, anti-smooth muscle autoantibodies, and hypergammaglobulinemia.

Question 2

A 32-year-old woman comes to the office due to postprandial abdominal pain and nausea.  The patient has no diarrhea, constipation, bloody stools, or vomiting.  Medical history is significant for rheumatoid arthritis.  The abdomen is mildly tender to palpation at the epigastrium but without distension or hepatosplenomegaly.  Laboratory studies reveal anemia.  A small gastric ulcer is seen during upper endoscopy, and biopsies are negative for Helicobacter pylori.  Biopsies of the duodenum reveal numerous intraepithelial lymphocytes, villous atrophy, and crypt hyperplasia.  Based on these biopsy findings, this patient is at increased risk for developing which of the following conditions later in life?

Accepted Answer

11ec160b_3930_bfc6_9249_67735228708a_MD0001_00 This patient's presentation (abdominal pain, anemia) and biopsy findings are suggestive of celiac disease, an immune-mediated disorder triggered by gluten, a protein found in wheat, barley, and rye. Diarrhea is also common in celiac disease but may be absent. Gliadin, a breakdown product of gluten, is primarily responsible for causing chronic inflammatory changes of the small bowel. Classic histologic findings, which are most prominent in the proximal small bowel (eg, duodenum, proximal jejunum), include intraepithelial lymphocytosis, villous atrophy, and crypt hyperplasia. Chronic lymphocytic recruitment and proliferation within the small-bowel mucosa predisposes to monoclonal T-cell expansion, putting these patients at risk for enteropathy-associated T-cell lymphoma. This small-bowel cancer is usually very aggressive and has a poor prognosis despite chemotherapy. (Choice A) Angiodysplasias are dilated, tortuous veins that develop in the gastrointestinal tract, most commonly in the small bowel and cecum. Risk factors include advanced age, chronic kidney disease, and aortic stenosis. They have no association with celiac disease. (Choice B) In addition to small-bowel lymphoma, celiac disease is a risk factor for small-bowel adenocarcinoma. Unlike ulcerative colitis, familial adenomatous polyposis, and Lynch syndrome, celiac disease does not predispose to colon adenocarcinoma. (Choice C) Portal vein thrombosis can create portal hypertension, predisposing to ascites and varices. This can occur in patients with hypercoagulable conditions such as polycythemia vera, as well as those with cirrhosis and hepatocellular carcinoma. Celiac disease does not predispose to portal vein thrombosis. (Choice D) Pyloric stenosis is a congenital disorder that results from pyloric smooth muscle hypertrophy and typically presents with profuse vomiting in infants. It is not associated with celiac disease. Educational objective: Celiac disease, an immune-mediated disorder triggered by gluten, causes small intestinal intraepithelial lymphocytosis, villous atrophy, and crypt hyperplasia. Monoclonal T-cell expansion can occur in the small-bowel mucosa of patients, leading to enteropathy-associated T-cell lymphoma.

Question 3

A 5-year-old boy is brought to the emergency department due to diarrhea and a low-grade fever.  He attends a day care center where other children developed similar symptoms.  The boy has no known medical problems.  He is up to date with age-appropriate vaccinations.  He has not traveled abroad.  Physical examination shows abdominal tenderness on deep palpation but no rigidity.  Stool is sent for culture, and the patient is diagnosed with Shigella sonnei infection.  The outbreak is reported to public health authorities and is traced to consumption of a potato salad handled by a food worker who recently had a mild diarrheal illness.  Which of the following cells are primarily responsible for uptake of the bacteria that initiated the infection in this boy?

Accepted Answer

Shigellosis is an infectious form of hemorrhagic diarrhea that can be caused by a variety of Shigella species (S dysenteriae, S flexneri, S boydii, S sonnei); shigellosis is most commonly due to S sonnei in industrialized nations (80%). Shigella cannot bind all intestinal cells. Shigella exhibits specificity for the microfold (M) cells at the base of mucosal villi within a Peyer patch region of the ileal mucosa. M cells sample gut lumen contents and transfer antigens to their basal lamina within endosomes. At the base of the cell, macrophages and lymphocytes ready to mount an immune response await within a special pocket (microfold). Shigella penetrates the mucous membrane by passing through M cells via endocytosis. It subsequently lyses the endosome, multiplies, and spreads laterally into other epithelial cells. This results in denuding and ulceration of the mucosa and subsequent leakage of blood, inflammatory elements, and mucus into the intestinal lumen. Patients pass frequent stools mixed with blood and mucus. Stools are frequent and loose due to water absorption inhibition. (Choice A) Endothelial cells form the innermost lining of blood vessels. The Shiga-like toxin of Escherichia coli O157:H7 can cause toxicity to renal endothelial cells, leading to renal insufficiency and uremia. (Choice B) Enteroendocrine cells in the gastrointestinal tract secrete hormones such as somatostatin and cholecystokinin. (Choice C) Goblet cells are responsible for mucus secretion into the gut lumen. Mucus release is increased in inflammatory states; stool will have visible mucus in conditions such as inflammatory diarrhea, giardiasis, and Crohn disease. (Choice E) Paneth cells, which occur in small groups at the base of intestinal crypts, are both phagocytic and secretory, thereby providing first-line immune defense against microorganisms. They secrete lysozyme (an enzyme that dissolves the cell walls of many bacteria) and defensins (polypeptides with antimicrobial properties). (Choice F) In patients with diarrhea, stool is tested for fecal leukocytes (polymorphonuclear cells) when it is unclear whether the etiology is noninflammatory (enterotoxigenic E coli, enteroaggregative E coli, Vibrio cholerae, Clostridium perfringens, Rotavirus) or inflammatory (Shigella, enterohemorrhagic E coli, enteroinvasive E coli, Clostridium difficile, Campylobacter jejuni). Educational objective: Shigellosis is an infectious disease that can be caused by variety of Shigella species; S sonnei is the most common cause of shigellosis in industrialized nations. Shigella invades the gastrointestinal mucosa by gaining access to microfold cells in ileal Peyer patches through endocytosis. Shigella subsequently lyses the endosome and spreads laterally into other epithelial cells, causing cell death and ulceration with hemorrhage and diarrhea.

Question 4

Rats exposed to high concentrations of carbon tetrachloride suffer rapid and extensive liver damage.  Light microscopic examination of affected liver specimens shows fatty change and hepatocyte necrosis.  These changes are the result of:

Accepted Answer

Carbon tetrachloride (CCl₄) causes free radical injury. Like many other toxic substances, CCl₄ is oxidized by the P450 oxidase system in the liver. The result is the formation of the free radical CCl₃, which reacts with structural lipids of cell membranes. The result is lipid degradation and hydrogen peroxide (H₂O₂) formation. This process is called lipid peroxidation. The peroxides go on to form new radicals, continuing the vicious circle of lipid degradation. Carbon tetrachloride cell injury develops rapidly and leads to swelling of the endoplasmic reticulum, destruction of mitochondria, and increased permeability of cell membranes. These processes culminate in hepatocyte necrosis. (Choices A and B) Hypoperfusion and hypoxia lead to tissue ischemia and necrosis. Carbon tetrachloride does not affect tissue oxygenation. (Choice C) Abnormal signal transduction is a mechanism of oncogenesis, as occurs with mutations of the Ras proto-oncogene. This mutation increases cell sensitivity to mitogenic influences. (Choice E) Mitochondrial dysfunction occurs in CCl₄ intoxication as a result of free radical injury. Educational Objective: The P450 microsomal oxidase system plays an important role in detoxification. In carbon tetrachloride poisoning, however, it produces free radicals that start a vicious cycle of hepatic injury.

Question 5

An 81-year-old woman is brought to the emergency department by a neighbor due to abdominal pain.  The pain comes in waves and is associated with nausea and vomiting.  The patient is confused and unable to provide additional information.  Past medical history is unknown, but she comes with a bag containing medications used in type 2 diabetes mellitus, hypercholesterolemia, hypertension, and dementia.  On examination, the patient has a low-grade fever and mild tachycardia.  She appears in distress due to pain.  Mucous membranes are dry, and there is decreased skin turgor.  Abdominal examination shows diffuse tenderness with high-pitched bowel sounds.  Imaging of the abdomen reveals a complete small bowel obstruction.  The patient undergoes laparotomy with extraction of a hard mass obstructing the ileocecal valve.  The cholesterol content of the mass is 85%.  Which of the following radiographic findings is most consistent with this patient's clinical presentation?

Accepted Answer

11ec160b_392f_3923_9249_9fb4b4e12770_MD0001_00 This patient, an older woman with intermittent abdominal pain and a cholesterol-containing mass lodged at the ileocecal valve, has a gallstone ileus. Gallstone ileus is not a true ileus (nonmechanical disruption of intestinal motility) but rather a mechanical obstruction that occurs when a large gallstone (usually >2.5 cm in diameter) erodes into the intestinal lumen through a cholecystoenteric fistula. As the gallstone travels down the intestine, it intermittently obstructs the lumen, causing episodic symptoms. Eventually, the gallstone may come to rest in the ileum, which has the smallest lumen of the intestinal tract. Typical symptoms of gallstone ileus include crampy pain, vomiting, and bloating. Examination will show signs of small bowel obstruction, such as abdominal distension, tenderness, and high-pitched (tinkling) bowel sounds. Abdominal radiographs may reveal dilated bowel loops with air-fluid levels. Careful inspection may also reveal air in the biliary tree (pneumobilia) due to retrograde passage of intestinal gas through the fistula. (Choice B) Bladder distension due to urinary retention is most often associated with underlying prostatic hyperplasia, anticholinergic medication use, and underlying neurologic impairment. (Choice C) Air in the peritoneal cavity is suggestive of bowel perforation. Although the bowel wall is disrupted in gallstone ileus, the cholecystoenteric fistula is usually associated with fibrotic adhesions between the biliary tree and the bowel, and there is no free communication with the peritoneal cavity. (Choice D) Heavily calcified vessels are a sign of chronic atherosclerotic arterial disease. Common intra-abdominal complications in such patients would include intestinal ischemia and abdominal aortic aneurysm. (Choice E) Pancreatic calcifications are suggestive of chronic pancreatitis, which is most commonly seen in alcohol abuse, cystic fibrosis, or outlet obstruction due to tumor, pseudocysts, or recurrent passage of gallstones. (Choice F) Pleural effusion may be seen in a broad range of intra-abdominal conditions, such as pancreatitis, esophageal rupture, or chronic hepatic or renal disease. Educational objective: Gallstone ileus is a mechanical bowel obstruction caused when a large gallstone erodes into the intestinal lumen. Pneumobilia (air in the biliary tract) is a common finding. __________ References: Gallstone ileus: case report and literature review. (http://www.ncbi.nlm.nih.gov/pubmed/24023505)

Question 6

A 35-year-old man is admitted to the hospital with a 2-day history of abdominal pain.  The patient's condition deteriorates throughout the course of hospitalization, and he dies 5 days after admission.  Autopsy reveals chalky white lesions in the mesentery.  Histologic evaluation of the lesions reveals adipose cell destruction and calcium deposition.  Which of the following is the most likely cause of this patient's autopsy findings?

Accepted Answer

This patient with abdominal pain and chalky white mesenteric lesions likely had acute pancreatitis. To prevent autodigestion, most pancreatic digestive enzymes (except for amylase and lipase) are secreted in an inactive form and are activated on arrival in the duodenum. In acute pancreatitis, intrapancreatic activation of enzymes result in acinar cell damage and pancreatic inflammation. The release of lipase and other digestive enzymes from the inflamed pancreas damages nearby adipose cells. Liberated fatty acids bind calcium ions, precipitating as insoluble calcium salts (ie, saponification) that have a chalky white appearance grossly. Microscopically, necrotic adipocytes (ie, anucleate adipocytes with necrotic debris) and blue calcium deposits are seen (compared to a normal pancreas). In mild cases, small areas of fat necrosis may be found within and around the pancreas, along with an edematous and inflamed pancreatic parenchyma. If the inflammatory process continues, acute necrotic pancreatitis develops. This is characterized by parenchymal necrosis and more extensive fat necrosis, which can spread to involve the mesentery, omentum, and other parts of the abdominal cavity (due to widespread lipase activity). Elastase-mediated destruction of blood vessel walls can cause hemorrhage into the necrotic areas (ie, hemorrhagic pancreatitis), and black hemorrhage may be seen grossly. (Choice B) Bacterial peritonitis is characterized by a dull-appearing peritoneal surface with areas of viscous white-yellow suppurative exudate. Microscopic examination of the ascitic fluid shows numerous neutrophils. (Choice C) In celiac disease, gross examination of an involved bowel segment would show normal-appearing serosa and mesentery. (Choice D) Crohn disease often shows mesenteric fat grossly extending around the serosa of an affected intestinal segment (ie, "creeping fat"). The serosa looks dull-gray, edematous, and granular. The mesentery of an involved segment may become fibrotic due to chronic inflammation. (Choice E) With intestinal perforation, a full-thickness defect in the intestinal wall is seen on gross examination. (Choice F) With mesenteric ischemia, gross examination of an affected bowel segment would show dusky red serosa, edema, and hemorrhagic mucosa. Microscopically, areas of coagulative necrosis may be present. Educational objective: In acute pancreatitis, release of lipase and other digestive enzymes causes fat necrosis with precipitation of insoluble calcium salts (ie, saponification), imparting a chalky white gross appearance. Microscopically, necrotic fat cells with calcium deposits are seen. In severe cases, fat necrosis can involve the mesentery, omentum, and other parts of the abdominal cavity.

Question 7

A 23-year-old man is hospitalized with acute pancreatitis that resolves rapidly on fasting.  He has suffered 2 similar episodes during the past 2 years.  A gallbladder ultrasound obtained during a previous episode was normal.  The patient has no other medical problems and takes no medications.  He does not consume alcohol.  Which of the following tests should be considered during the workup of this patient?

Accepted Answer

Gallstones and alcohol use are the most common causes of acute pancreatitis. Gallstones typically affect middle-aged and older patients (particularly women) unless there is a predisposing condition (eg, young patients with sickle cell disease are at increased risk for bilirubin gallstones). This young male patient does not consume alcohol and is unlikely to have gallstones, especially considering the negative results of his prior ultrasound. Thus, one of the following less common causes of acute pancreatitis likely accounts for his condition: High levels of circulating triglycerides lead to increased production of free fatty acids within the pancreatic capillaries by pancreatic lipase. Normally, fatty acids exist in serum bound to albumin. However, if serum triglyceride levels rise to >1000 mg/dL, the concentration of free fatty acids exceeds the binding capacity of albumin and leads to direct injury to the pancreatic acinar cells. Thus, hypertriglyceridemia causes acute pancreatitis via direct tissue toxicity. (Choice A) Decreased serum ceruloplasmin and increased hepatic copper content are diagnostic of Wilson disease. Cirrhosis, central nervous system involvement, and Kayser-Fleischer rings are characteristic findings. Wilson disease does not predispose to acute pancreatitis. (Choice B) Increased serum cholesterol levels predispose to the development of systemic atherosclerosis, putting patients at increased risk for coronary artery disease, peripheral vascular disease, and stroke. In some cases, hypercholesterolemia may increase the risk of cholesterol gallstone formation, but this patient's negative gallbladder ultrasound makes this a less likely cause of his pancreatitis. (Choice C) High concentrations of serum ferritin are found in hemochromatosis. Hemochromatosis can cause cirrhosis, pancreatic fibrosis and subsequent diabetes, cardiomyopathy, and secondary hypogonadism. It does not cause acute pancreatitis. (Choice E) Hyperuricemia can lead to the formation of uric acid renal calculi and urate nephropathy. There is no association with acute pancreatitis. (Choice F) Increased concentrations of oxalate in the urine are associated with intestinal malabsorption syndromes (eg, Crohn disease). Calcium oxalate renal stones may form as a result. Hyperoxaluria is not associated with acute pancreatitis. Educational objective: Eighty percent of acute pancreatitis cases are caused by gallstones and chronic alcoholism. Less common causes account for the other 20%. Inherited or acquired hypertriglyceridemia can cause acute pancreatitis if the serum level of triglycerides exceeds 1000 mg/dL.

Question 8

A 48-year-old woman comes to the office due to heavy menstrual bleeding for the last several months. The patient has monthly menses with 5-6 days of heavy bleeding and passage of large blood clots and increased abdominal cramping. She has no significant medical history and has had 2 vaginal deliveries. Her family history is significant for endometrial cancer in her mother. BMI is 24 kg/m². Vital signs are normal. Pelvic ultrasound shows a uterine mass. The patient undergoes a total abdominal hysterectomy; gross examination of the uterus is shown below: The abnormal region indicated by the arrow is most likely to display which of the following microscopic findings?

Accepted Answer

11ec160b_3926_8687_9249_5fd7503cf310_MD0001_00 This patient with heavy menses and a uterine mass has a uterine leiomyoma, also known as a fibroid. Fibroids are common, benign tumors arising from smooth muscle cells and fibroblasts that can grow in a variety of sizes and locations within the uterine myometrium, resulting in variable clinical presentations. This patient has an intramural fibroid (within the uterine wall), which can increase the endometrial surface area (due to mass effect) and result in heavy menses. Patients with symptomatic uterine fibroids are often treated surgically with a hysterectomy. Grossly, fibroids appear as discrete, yellow-gray tumors with a thin pseudocapsule that separates the fibroid from the normal uterine myometrium. Diagnosis is confirmed with microscopy, which typically reveals monoclonal proliferation of myocytes and fibroblasts because each fibroid arises from a single progenitor smooth muscle cell. Due to their benign nature, fibroid myocytes are uniform in size and shape and have minimal mitotic figures. (Choice A) Patients with cervical cancer are often asymptomatic or have irregular, postcoital spotting rather than heavy menses. Cervical cancer is typically found in the cervical transformation zone (rather than the uterine myometrium) and microscopy shows dysplastic squamocolumnar cells with areas of atypia. (Choice B) Patients with endometriosis typically present with painful menses (ie, dysmenorrhea); however, there are usually endometrial tissue implants outside the uterus rather than an intrauterine mass. Light microscopy typically reveals ectopic endometrial glands and hemosiderin-laden macrophages. (Choice C) Patients with endometrial hyperplasia or cancer typically present with irregular, heavy menses and a thickened endometrium (rather than a mass in the myometrium). Histopathology typically reveals hyperplastic proliferation of irregular endometrial glands. (Choice D) Microscopy of ovarian cancer typically reveals infiltration of the stroma by high-grade serous carcinoma. Ovarian cancer is unlikely in this patient as it typically causes an adnexal mass rather than a solitary intrauterine mass. Educational objective: Uterine leiomyomas (ie, fibroids) are common, benign tumors arising from the uterine myometrium that occur due to monoclonal proliferation of myocytes and fibroblasts. __________ References: Clonality of smooth muscle and fibroblast cell populations isolated from human fibroid and myometrial tissues. (http://www.ncbi.nlm.nih.gov/pubmed/24243625)

Question 9

A 40-year-old man comes to the office with pain on defecation.  The pain is sharp and severe but subsides within minutes of passing the bowel movement.  He often sees spots of bright red blood on the toilet paper.  The patient has chronic constipation and has not taken laxatives or increased his fluid intake to compensate.  He has no fever, night sweats, diarrhea, or unexpected weight loss.  Past medical history is notable for chronic low back pain following a motor vehicle accident, for which he takes a scheduled dose of pain relievers.  The patient has smoked a pack of cigarettes daily for the last 20 years but does not use alcohol or illicit drugs.  He is married and has no outside sexual contacts.  Vital signs are normal.  The abdomen is soft and nontender with no hepatosplenomegaly.  Rectal examination is likely to show a tear at which of the following locations?

Accepted Answer

11ec160b_392d_8b6e_9249_5122a9ae63cd_MD0001_00 This patient has sharp pain and bright red rectal bleeding on defecation, suggesting an anal fissure. Anal fissures are due to stretching of the mucosa and are characterized by longitudinal tears in the anal canal distal to the dentate line (Choice B). Spasm of the sphincter can contribute to the pain and create tension across the wound, leading to a chronic fissure. Most fissures are related to chronic constipation with high anal pressures and passage of hard stools. They can also be seen with frequent diarrhea or anal sexual intercourse. In some cases, the pain may be so severe that patients withhold bowel movements, thereby exacerbating the constipation. The majority of fissures, especially those causing prolonged symptoms, occur at the posterior midline of the anal verge. This is likely due to the relatively poor perfusion of the posterior anal canal, which makes its mucosa sensitive to trauma and slows healing times. Anterior midline fissures are less common, but may occur due to mechanical stresses related to the alignment of muscular fibers in the external sphincter (Choice A). (Choice C) Bilateral anal fissures are uncommon. (Choices D and E) Fissures not at the midline are more likely due to unusual causes (eg, inflammatory bowel disease, malignancy, infection) and may warrant more detailed investigation. Educational objective: Anal fissures are longitudinal tears in the mucosa. They are usually due to passage of hard stool in patients with chronic constipation. Most fissures occur at the posterior midline, likely due to decreased blood flow in this area. Fissures in other areas may be due to less common causes. __________ References: Anorectal conditions: anal fissure and anorectal fistula. (http://www.ncbi.nlm.nih.gov/pubmed/24742084)

Question 10

A 49-year-old man comes to the office for evaluation of a dry cough that occurs mainly at night.  His symptoms have been present on and off for several years, but he has not been previously evaluated.  The patient also reports a frequent sore throat and occasional epigastric discomfort.  He has tried a variety of antihistamines and over-the-counter cough medications without relief.  Past medical history is notable for obesity and diet-controlled type 2 diabetes mellitus.  He does not smoke or drink alcohol.  Cardiopulmonary and abdominal examinations are unremarkable.  Chest x-ray reveals no abnormalities, and pulmonary function testing is normal.  The patient undergoes upper gastrointestinal endoscopy with mucosal biopsies.  Microscopic findings on lower esophageal biopsy are shown in the image below.  This patient is at highest risk of which of the following complications?

Accepted Answer

11ec160b_392e_9ce2_9249_659a2ea180ec_MD0001_00 This patient's persistent dry cough, sore throat, and epigastric discomfort is suggestive of gastroesophageal reflux disease. His esophageal biopsy shows intestinal-type columnar epithelium with goblet cells where a normal esophagus would be lined by stratified squamous epithelium. This finding is diagnostic of Barrett esophagus, which is seen when acidic gastric contents enter the esophagus, causing inflammation and subsequent epithelial necrosis. Sustained epithelial damage promotes metaplastic replacement of the normal stratified squamous epithelium with intestinal-type columnar cells. The transition to columnar epithelium may be seen grossly on endoscopy as tongues of beefy red mucosa extending above the lower esophageal sphincter into areas of normal pale pink squamous mucosa. People with severe and long-standing acid reflux are most prone to Barrett esophagus. This metaplasia is hypothesized to be adaptive at first, as intestinal-type epithelium is more resistant to gastric acid. However, it is a major risk factor for esophageal adenocarcinoma, which typically develops from the metaplastic intestinal epithelium in the distal part of the esophagus. (Choices A and D) The major risk factors for squamous cell carcinoma of the esophagus are cigarette smoking and alcohol use. Achalasia, an esophageal motility disorder caused by the loss of ganglion cells in the lower esophagus, also carries an increased risk of squamous carcinoma. (Choices C and E) Crohn disease can affect the esophagus, typically causing patchy inflammation, erosions, ulcers, strictures, and fistulas. Esophageal varices develop in the context of high portal venous pressure, most often due to alcohol-induced or post-viral liver cirrhosis. These conditions are not associated with Barrett esophagus. Educational objective: Barrett esophagus is a metaplastic condition in which the normal squamous epithelium of the distal esophagus is replaced by intestinal-type columnar epithelium. It occurs most often in longstanding acid reflux and is associated with an increased risk of adenocarcinoma.

Question 11

A 5-month-old boy is being evaluated for poor weight gain since birth.  He is noted to have bulky and greasy stools.  A jejunal biopsy shows the findings seen in the slide below.  Which of the following is the most likely diagnosis?

Accepted Answer

11ec160b_3926_fbb9_9249_3908314eee0c_MD0001_00 The slide above shows normal intestinal mucosal architecture, but the enterocytes contain clear or foamy cytoplasm which is more prominent at the tips of the villi. These findings occur due to accumulation of lipids in the absorptive cells of the intestinal epithelium and are typical of abetalipoproteinemia, a disease caused by impaired formation of apolipoprotein B (apoB)-containing lipoproteins. Dietary lipids are normally processed in small-bowel enterocytes and secreted as chylomicrons; endogenously produced lipids are secreted from liver hepatocytes as very low-density lipoprotein (VLDL). Chylomicron and VLDL particles are synthesized within the endoplasmic reticulum as lipids accumulate around a single apoB molecule. ApoB-100 is found in VLDL, and apoB-48 (a truncated version without the LDL receptor ligand) is present in chylomicrons. During the synthesis of apoB-containing lipoproteins, microsomal triglyceride transfer protein (MTP) functions as a chaperone protein necessary for proper folding of apoB and also participates in the transfer of lipids to newly formed chylomicrons and VLDL particles. Abetalipoproteinemia is most commonly caused by an autosomal recessive, loss-of-function mutation in the MTP gene. It manifests during the first year of life with symptoms of malabsorption (eg, abdominal distention, foul-smelling stool). Laboratory studies show very low plasma triglyceride and cholesterol levels; chylomicrons, VLDLs, and apoB are entirely absent from the blood. Poor lipid absorption causes deficiency of fat-soluble vitamins (particularly vitamin E) and essential fatty acids. This results in red blood cells with abnormal membranes and thorny projections called acanthocytes as well as multiple neurologic abnormalities (eg, progressive ataxia, retinitis pigmentosa). (Choice B) Light microscopy shows atrophy and blunting of the villi in celiac disease. Chronic inflammatory infiltrate of the lamina propria is also present. These features are not seen in the slide above. (Choices C, E, and G) No abnormalities are found on light microscopy of the small intestine in chronic pancreatitis or lactase deficiency. In Zollinger-Ellison syndrome, the small intestine may show ulcerations due to gastrin production by a neuroendocrine tumor (ie, gastrinoma). (Choice D) Light microscopy in Crohn disease shows chronic inflammation of all layers of the intestinal wall and noncaseating granulomas. (Choice F) The characteristic microscopic finding in Whipple disease is distended macrophages in the lamina propria of the small intestine. Macrophages contain PAS-positive and diastase-resistant granules and rod-shaped Tropheryma whipplei bacilli. Educational objective: Abetalipoproteinemia is an inherited inability to synthesize apolipoprotein B, an important component of chylomicrons and very low-density lipoprotein. Lipids absorbed by the small intestine cannot be transported into the circulation and instead accumulate in the intestinal epithelium, resulting in enterocytes with clear or foamy cytoplasm.

Question 12

A 38-year-old woman comes to the hospital with 4 hours of abdominal pain, nausea, and vomiting.  Her pain started in the periumbilical area and is now localized to the right lower quadrant.  Temperature is 38.3 C (101 F).  On examination, the patient has right lower quadrant tenderness with guarding.  An appendectomy is performed, and light microscopy of the appendix shows infiltrating neutrophils in the muscularis propria, consistent with the diagnosis of acute appendicitis.  Further evaluation reveals abnormal islands of small cells, as shown in the image below.  These cells are most likely derived from which of the following sources?

Accepted Answer

The image shows the typical microscopic appearance of a carcinoid tumor. Note the uniformity in shape and size of the cells that comprise the islands. Trabeculae, glands, strands, or sheets of cells may also be formed. Tumor cells have an eosinophilic cytoplasm and oval-to-round stippled nuclei. On electron microscopy, multiple dense-core granules are seen in the cytoplasm; these contain secretory products such as vasoactive molecules (eg, serotonin, bradykinin, histamine) and hormones (eg, gastrin). Carcinoid tumors are malignant transformations of neuroendocrine cells, most commonly located in the gastrointestinal tract (eg, small intestine, rectum, appendix), followed by the bronchopulmonary system. The majority of appendiceal carcinoids have a benign clinical course. They are usually found at the tip of the appendix in asymptomatic patients who have undergone appendectomy for unrelated reasons. Tumors at the base of the appendix may cause obstruction and appendicitis. In rare cases, large tumors will metastasize to the liver, causing carcinoid syndrome (flushing, diarrhea, bronchospasm). (Choice A) Connective tissue can be a source of both benign (fibromas) and malignant (fibrosarcomas) tumors. (Choice B) Abnormal proliferation of hematopoietic cells leads to a variety of myeloid and lymphoid neoplasms. (Choice C) Intestinal epithelial cells (both absorptive and mucus-secreting) can give rise to intestinal adenocarcinomas. (Choice E) Smooth muscle cells give rise to leiomyomas and leiomyosarcomas. (Choice F) Vascular endothelial cells can be a source of benign (hemangioma), intermediate (hemangioendothelioma), and malignant (angiosarcoma) tumors. Educational objective: Carcinoid tumors are composed of islands or sheets of uniform cells with eosinophilic cytoplasm and oval-to-round stippled nuclei. These tumors are often derived from neuroendocrine cells in the gastrointestinal tract. Appendiceal carcinoids typically have a benign course but may cause appendicitis or, rarely, carcinoid syndrome (eg, with liver metastasis). __________ References: Updated population-based review of carcinoid tumors. (http://www.ncbi.nlm.nih.gov/pubmed/15213627) Carcinoid tumor of the appendix: A case report. (http://www.ncbi.nlm.nih.gov/pubmed/26137079) Gastrointestinal neuroendocrine/neuroectodermal tumors. (http://www.ncbi.nlm.nih.gov/pubmed/11993693)

Question 13

A 40-year-old female presented to the physician for evaluation of worsening fatigue.  She has no other medical problems.  She does not use tobacco, alcohol or drugs.  Vital signs are within normal limits.  Physical examination is within normal limits.  Laboratory evaluation shows an alkaline phosphatase level of 180 U/L.  Which of the following should be checked next?

Accepted Answer

Broadly speaking, laboratory tests used in the evaluation of hepatobiliary disease either assess liver functionality (eg, prothrombin time, bilirubin, albumin, cholesterol) or the structural integrity and cellular intactness of the liver (eg, transaminases) or the biliary tract (eg, alkaline phosphatase, γ-glutamyl transferase). Alkaline phosphatase represents a group of enzymes associated with metabolic activity in a number of tissues, including liver, bone, intestine, kidney, placenta, leukocytes, and some neoplasms. Bone and liver are the primary sources of alkaline phosphatase, with threefold elevations considered a relatively nonspecific finding for many liver diseases. To clarify the importance of a moderately elevated alkaline phosphatase, the hepatic γ-glutamyl transpeptidase (GGTP) should be evaluated. γ-glutamyl transpeptidase is an enzyme predominantly present in hepatocytes and biliary epithelia. While it too can be found in various extrahepatic tissues (organs such as kidney, spleen, pancreas, heart, lung, and brain), GGTP is not present to a significant extent in bone. It is therefore particularly useful in determining whether an elevated alkaline phosphatase is of hepatic or bony origin. (Choice A) Measurement of unconjugated bilirubin (especially in contrast to conjugated bilirubin) can be of assistance in distinguishing hemolytic conditions from hepatic dysfunction or bile duct obstruction. This test is not particularly helpful in following up an elevated alkaline phosphatase. (Choice B) Lactate dehydrogenase is a relatively nonspecific test that can be of some assistance in the evaluation of tissue injury or death. It is not the most helpful test in following up an elevated alkaline phosphatase. (Choice C) Serum ammonia levels can be of assistance in determining the extent of liver failure or gastrointestinal bleeding, among other conditions. It is not the most helpful test in following up an elevated alkaline phosphatase. (Choice D) Prothrombin time is of assistance in assessing coagulative ability and liver functionality, especially in the acute setting. It is not the most helpful test in following up an elevated alkaline phosphatase. (Choice F) Aspartate aminotransferase is of assistance in assessing and monitoring hepatic damage. It is not the most helpful test in following up an elevated alkaline phosphatase. Educational Objective: A moderately elevated alkaline phosphatase of unclear etiology should be followed up with γ-glutamyl transpeptidase.

Question 14

A 6-year-old girl is brought to the office due to intermittent abdominal cramps, bloating, and diarrhea for 2 months.  She also has excessive flatulence, which typically occurs after meals.  The patient has had no fever or vomiting.  She eats a well-balanced diet and takes no medications or vitamins.  Vital signs are appropriate for age.  Examination shows a mildly distended abdomen with no hepatosplenomegaly or tenderness.  Laboratory evaluation reveals elevated tissue transglutaminase antibodies.  Which of the following locations should be biopsied to confirm the diagnosis in this patient?

Accepted Answer

11ec160b_3930_4a95_9249_7bb438b5f7f4_MD0001_00 This patient with chronic gastrointestinal symptoms and elevated tissue transglutaminase (TTG) antibodies likely has celiac disease. This chronic, malabsorptive disorder is caused by an immune-mediated reaction to dietary gliadin (the major component of gluten) found in wheat, barley, and rye. In patients with celiac disease, gliadin triggers an inflammatory reaction within the small intestine that leads to the classic symptoms of abdominal pain, distension, flatulence, and diarrhea. Laboratory evaluation usually reveals antibodies against TTG, a crosslinking enzyme that interacts with glutamine-rich proteins (including exogenous gliadin). Endoscopy with biopsy characteristically shows villus atrophy, lymphocytic infiltration of the intraepithelial cells, and crypt hyperplasia. Biopsy of the duodenum and proximal jejunum are most likely to confirm the diagnosis because these areas of the intestine are exposed to the highest concentration of gliadin. (Choice A) Helicobacter pylori infection, which predisposes to gastritis and peptic ulcer disease, can cause abdominal pain (often postprandial) and bloating, and gastric biopsy can confirm the diagnosis. However, elevated TTG antibodies are not associated with H pylori. (Choices C, D, and E) Because celiac disease primarily involves the proximal small bowel, biopsies from the distal jejunum and terminal ileum may be normal in patients with celiac disease and are not recommended; the colon is not affected in celiac disease. Educational objective: Celiac disease is caused by an immune-mediated reaction to gluten and classically leads to chronic gastrointestinal symptoms. Diagnosis is confirmed by elevated tissue transglutaminase IgA antibody levels and duodenal biopsy showing villus flattening, intraepithelial lymphocyte infiltration, and crypt hyperplasia.

Question 15

A 43-year-old man comes to the office due to yellowing of the skin over the past several days.  He has had no fever or abdominal pain and has not traveled recently or received blood transfusions.  The patient has also experienced increased shortness of breath with exercise over the past few months.  He has no other medical conditions and takes no medications.  The patient drinks 1 or 2 glasses of wine on social occasions and does not use tobacco or illicit drugs.  His father died of liver cirrhosis attributed to alcohol use.  On physical examination, expiration is prolonged and there are scattered bilateral wheezes.  Laboratory results show total bilirubin of 4.1 mg/dL and alanine aminotransferase of 90 U/L.  Viral hepatitis serology is negative.  Chest x-ray shows hyperlucency of lung fields and flattening of the diaphragm.  Abdominal ultrasound reveals increased liver span and echogenicity of the liver parenchyma but no masses.  Which of the following is the most likely underlying cause of this patient's symptoms?

Accepted Answer

11ec160b_392c_a10d_9249_eb8c68e20a85_MD0001_00 This patient with signs of liver dysfunction (ie, jaundice, transaminitis) and evidence of emphysema on chest x-ray (eg, hyperlucency, diaphragmatic flattening) likely has alpha-1 antitrypsin deficiency (AATD). Alpha-1 antitrypsin is a serine protease inhibitor that regulates the activity of a number of tissue-destructive proteases, most importantly neutrophil elastase. Deficiency is inherited in an autosomal codominant fashion. AATD leads to unchecked elastase activity in the lungs, resulting in alveolar destruction and lung hyperinflation; the panacinar emphysema tends to favor the basilar lung regions and typically develops prior to age 50. In addition, some patients can develop liver disease due to accumulation of improperly folded alpha-1 antitrypsin proteins in hepatocytes. Liver disease is of greatest concern in the first 2 decades of life, but it can present in any decade. Patients can experience hepatomegaly, hyperbilirubinemia, elevated transaminases, and eventual cirrhosis and end-stage liver disease. Hepatocellular carcinoma may also develop. (Choice A) Autoimmune injury of intrahepatic bile ducts occurs in primary biliary cholangitis (PBC, formerly primary biliary cirrhosis). PBC predominantly affects women and is characterized by positive antimitochondrial antibodies. It is not associated with emphysema. (Choice B) UDP-glucuronosyltransferase is an enzyme that converts unconjugated bilirubin to its conjugated form, and inherited deficiency can exist in varying degrees. Mild deficiency results in benign elevations in unconjugated bilirubin during periods of stress (ie, Gilbert syndrome), while severe deficiency can be fatal during infancy (ie, Crigler-Najjar syndrome type I). (Choice C) Defective epithelial chloride transport occurs in cystic fibrosis. Patients typically develop obstructive lung disease in the form of bronchiectasis and can have pancreatic insufficiency leading to malabsorption. In addition, cirrhosis can sometimes occur. Cystic fibrosis usually presents during childhood; onset of disease manifestations at age >40 would be highly unusual. (Choice D) Defective copper transport resulting in accumulation of intracellular copper occurs in Wilson disease. Patients can develop cirrhosis as well as brain degeneration leading to neurologic (eg, dysarthria, gait abnormalities) and psychiatric (eg, impulsivity) manifestations. (Choice F) Unregulated gastrointestinal iron absorption occurs in hemochromatosis. Patients can develop cirrhosis due to iron overload. The joints (arthritis), pancreas (diabetes mellitus), and heart (cardiomyopathy) are also commonly affected, but lung involvement is not typical. Educational objective: Alpha-1 antitrypsin (AAT) is a serine protease inhibitor that regulates the activity of elastase in the lung. Inherited deficiency of AAT leads to alveolar destruction and panacinar emphysema; in addition, accumulation of improperly folded AAT proteins in hepatocytes can lead to liver dysfunction and cirrhosis in some patients. __________ References: Diagnosis and management of patients with a1-antitrypsin (A1AT) deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/22200689) An update on laboratory diagnosis of liver inherited diseases. (http://www.ncbi.nlm.nih.gov/pubmed/24222913)

Question 16

A 68-year-old woman comes to the emergency department due to shortness of breath, poor appetite, and abdominal distension for the past 3 months.  Her symptoms have progressively worsened, and now she is unable to perform her daily activities.  The patient has a history of coronary artery disease and underwent coronary artery bypass grafting 3 years ago.  She also has myelodysplastic syndrome for which she receives intermittent blood transfusions.  Physical examination shows jugular venous distension, abdominal distension, hepatomegaly, and lower extremity edema.  A representative liver biopsy image is shown in the exhibit. 
 Which of the following is the most likely cause of this patient's liver findings?

Accepted Answer

11ec160b_3929_6cba_9249_3d6f7fc2a024_MD0001_00 This patient's shortness of breath-accompanied by abdominal distension (ascites), hepatomegaly, jugular venous distension, and lower extremity edema-is consistent with right-sided heart failure; her liver biopsy demonstrates evidence of congestive hepatopathy. In congestive hepatopathy, outflow of blood from the hepatic veins is impeded by elevated right atrial and vena caval pressures, which leads to increased hydrostatic pressure in the central veins of the liver. There is consequent seepage of fluid into the surrounding hepatocytes with resulting congestion and hepatic necrosis. The hepatocellular damage favors the centrilobular areas (zone 3) where congestion is most prominent. On microscopy, patchy hemorrhage is seen surrounding the central veins consistent with centrilobular necrosis. These areas of necrosis contrast with the relatively normal-appearing hepatocytes in the periportal regions (zone 1), creating an overall heterogenous appearance sometimes referred to as "nutmeg liver." In addition to signs and symptoms of right-sided heart failure, patients with congestive hepatopathy may have localized right upper quadrant pain (due to stretching of the hepatic capsule), and laboratory results may demonstrate modest elevations in serum bilirubin and transaminases. (Choice A) Autoimmune destruction of intrahepatic biliary ducts occurs in primary biliary cholangitis (formerly primary biliary cirrhosis). Because intrahepatic bile ducts are concentrated in the periportal regions, histopathology demonstrates periductal fibrosis predominantly in those regions. (Choice B) Excessive hepatic deposition of iron most commonly occurs due to hemochromatosis. Patients receiving frequent blood transfusions are also at risk; however, histopathology would demonstrate periportal fibrosis and numerous brown pigments representing iron deposits. Fibrosis favors the periportal regions likely because those hepatocytes are exposed to the highest concentrations of iron-rich blood coming from the portal vein. (Choice C) Histopathology in chronic viral hepatitis (eg, chronic hepatitis C) reveals dense infiltrate of mononuclear inflammatory cells in the periportal regions; there is often gradual development of periportal fibrosis that may eventually bridge to the centrilobular regions. (Choice D) Histopathology of metastatic spread to the liver is unlikely to demonstrate a consistent pattern of lobular necrosis, but it can reveal an abrupt demarcation between normal hepatocellular tissue and the metastatic tumor. Educational objective: Congestive hepatopathy is a common complication of right-sided heart failure. Patchy hemorrhage and necrosis predominantly affect the centrilobular regions (zone 3) where hepatic congestion is most prominent. The centrilobular necrosis, combined with relatively normal-appearing periportal regions (zone 1), creates an overall heterogenous appearance sometimes referred to as "nutmeg liver."

Question 17

A 48-year-old male is admitted to the hospital with severe epigastric abdominal pain and vomiting after an episode of binge-drinking.  Four weeks later, he is found to have a palpable upper abdominal mass and a cystic lesion is visualized on computed tomography scanning (see image below, asterisk marks the lesion).  The inner walls of the lesion are most likely lined with:

Accepted Answer

This CT image shows a pancreatic pseudocyst, a potential complication of pancreatitis. In acute pancreatitis, proteolytic enzymes may disrupt the walls of the pancreatic ducts and cause leakage of pancreatic secretions into the peripancreatic space. This fluid has a high pancreatic enzyme content and induces an inflammatory reaction in the walls of the surrounding organs. Granulation tissue forms, encapsulating the fluid collection and forming a pseudocyst. In contrast to a true cyst with walls lined by epithelial cells, the walls of a pseudocyst consist of granulation tissue and no epithelial lining. Fibrosis, thickening and organization of the walls occur with time. The formation of firm fibrotic pseudocyst walls ("maturation" of the pseudocyst) takes about 4 to 6 weeks following the episode of acute pancreatitis. The most common location for a pseudocyst is in the lesser peritoneal sac, bordered by the stomach, duodenum and transverse colon. The pseudocyst walls are closely adherent to the surrounding hollow organs. The pseudocyst in the CT image above is located in the lesser sac, posterior to the stomach. (Choice A) Glycogen-rich cuboidal epithelium is seen in serous pancreatic neoplasms. (Choice B) Columnar mucinous epithelium is typically found in mucinous cystic neoplasms of the pancreas. (Choice C) Atypical cells forming papillary projections are seen in the papillary variant of pancreatic adenocarcinoma. (Choice E) Endothelial cells are not found in the wall of the pseudocyst. Educational Objective: Pancreatic pseudocyst is a common complication of acute pancreatitis. It is a collection of fluid rich in enzymes and inflammatory debris. Its walls consist of granulation tissue and fibrosis. Unlike true cysts, pseudocysts are not lined by epithelium.

Question 18

A 32-year-old man with mild abdominal discomfort and anorexia admits consuming large amounts of alcohol recently.  He undergoes a liver biopsy, which shows the light microscopy findings seen in the image below.  Which of the following is the most likely cause of this patient's condition?

Accepted Answer

Hepatic steatosis is a nonspecific condition characterized by triglyceride accumulation within the hepatocellular cytoplasm. The pathogenesis of alcohol-induced hepatic steatosis appears related primarily to a decrease in free fatty acid oxidation secondary to excess NADH production by the 2 major alcohol metabolism enzymes, alcohol dehydrogenase and aldehyde dehydrogenase. Contributing pathogenetic factors include impaired lipoprotein assembly and secretion and an increase in peripheral fat catabolism. As seen in the image, fatty tissue that is routinely fixed will microscopically demonstrate cytoplasmic vacuoles as the lipid is dissolved during histologic processing. In frozen sections, lipids can be demonstrated by staining with oil red O or Sudan black. (Choice A) Alcohol-induced hepatic steatosis is associated with increased (not decreased) triglyceride synthesis. (Choice C) Increased peripheral fat (not phospholipid) catabolism is associated with alcohol-induced hepatic steatosis. (Choice D) Impaired (not enhanced) lipoprotein assembly is associated with alcohol-induced hepatic steatosis. (Choice E) Alteration of the hepatic NAD/NADH ratio due to alcohol consumption induces fatty liver through inhibition of gluconeogenesis and fatty acid oxidation. (Choice F) Increased glucose uptake into cells occurs when high insulin levels are circulating; this condition is not associated with hepatic steatosis. Educational objective: The pathogenesis of alcohol-induced hepatic steatosis appears related primarily to a decrease in free fatty acid oxidation secondary to excess NADH production by the 2 major alcohol metabolism enzymes, alcohol dehydrogenase and aldehyde dehydrogenase.

Question 19

A 45-year-old man comes to the emergency department due to sudden-onset vomiting and severe upper abdominal pain that radiates to his back.  The patient's total bilirubin is 0.9 mg/dL, aspartate aminotransferase (AST) is 98 U/L, alanine aminotransferase (ALT) is 32 U/L, and alkaline phosphatase is 98 U/L.  Serum lipase is markedly increased.  Abdominal ultrasound reveals a normal gallbladder and common bile duct.  The diagnosis of acute pancreatitis is made, and a specific etiology is established.  Which of the following additional laboratory findings is most specific for the underlying cause of this patient's pancreatitis?

Accepted Answer

This patient's acute pancreatitis is likely related to chronic alcohol use given his >2 AST:ALT ratio and absence of gallstones on abdominal ultrasound. After gallstones, alcohol use is the second most common cause of acute pancreatitis. Ethanol induces pancreatic secretions with a high protein concentration and low fluid content. These viscous secretions are prone to precipitate and form plugs that can obstruct the lumina of the pancreatic ductules. Alcohol also causes spasms of the sphincter of Oddi and has a direct toxic effect on the acinar cells. Alcohol-related acute pancreatitis is clinically indistinguishable from pancreatitis due to other causes. However, chronic alcohol use causes a number of systemic effects due to both the direct toxic actions of ethanol and alcohol-associated vitamin deficiencies. Even in the absence of anemia, macrocytosis (mean corpuscular volume >100 fL) is often seen and is likely related to poor nutrition (eg, folate deficiency), liver disease, and/or direct toxicity of alcohol on the marrow. (Choice B) In severe acute pancreatitis, necrosis can spread into the retroperitoneal fat, omentum, mesentery, and even beyond the abdominal cavity. Large amounts of calcium bind to the released free fatty acids, forming soaps that are deposited in the areas of necrosis, which may result in hypocalcemia. However, this is a nonspecific finding that can occur with pancreatitis of any etiology, not just alcohol-related pancreatitis. (Choice C) Inflammation in acute pancreatitis may lead to dysfunction of the pancreatic islets with decreased secretion of insulin, resulting in hyperglycemia. This is a nonspecific finding that can occur with pancreatitis of any etiology, not just alcohol-related pancreatitis. (Choice D) Hypernatremia may occur in the setting of severe acute pancreatitis due to large third-space fluid loss (ie, interstitial fluid accumulation) and decreased water intake, causing subsequent hypovolemia and renal sodium retention. This finding is also not specific for alcohol-related pancreatitis. (Choice E) An increased white blood cell count is a nonspecific marker of inflammation and may occur with pancreatitis of any etiology. Educational objective: After gallstones, chronic alcohol use is the second most common cause of acute pancreatitis. Macrocytosis and an AST:ALT ratio >2 are indirect indicators of chronic alcohol consumption. Alcohol-related macrocytosis can occur independently of folate deficiency. __________ References: Pathophysiology of alcoholic pancreatitis: an overview. (http://www.ncbi.nlm.nih.gov/pubmed/17167828) Diagnosis of alcoholic liver disease. (http://www.ncbi.nlm.nih.gov/pubmed/25206273) Traditional markers of excessive alcohol use. (http://www.ncbi.nlm.nih.gov/pubmed/14984240)

Question 20

A 22-year-old Caucasian male presents to the ER with abdominal pain that started around his bellybutton, then moved to the right lower abdominal quadrant.  After initial evaluation, laparotomy is performed, which reveals the following findings (see the slide below).  Which of the following most likely initiated this patient's condition?

Accepted Answer

An inflamed, hyperemic, and edematous appendix is shown above. This macroscopic appearance, along with periumbilical pain that migrates to the right lower quadrant, is classic for acute appendicitis. This condition occurs in all age groups, with peak incidence in children 6-10 years old. The abdominal pain tends to appear in the periumbilical area (visceral pain) and shifts to the right lower quadrant a few hours later. Acute appendicitis is caused by an obstruction of the appendicular lumen. The most common obstructing agents are fecaliths. Obstruction by hyperplastic lymphoid follicles, foreign bodies, nematodes, and carcinoids may also cause acute appendicitis. Retained mucus causes the appendicular wall to distend, which impairs venous outflow. The resulting hypoxia causes ischemia and associated bacterial invasion. Inflammation and edema of the appendicular wall occur, causing further distention. Necrosis of the wall with rupture may follow. In this case, inflammatory fluid and bacterial contents spill into the peritoneal cavity, causing peritonitis. (Choice A) Bacterial infection plays an important role in the pathogenesis of acute appendicitis. It is not, however, the initiating event. (Choice B) Peptic ulceration is implicated in the development of lower intestinal bleeding due to Meckel diverticulum, not acute appendicitis. (Choices D and E) Both venous thrombosis and arterial spasm can cause mesenteric ischemia; however, neither of these factors lead to acute appendicitis. Educational Objective: Obstruction of the lumen of the appendix is the first event in pathogenesis of acute appendicitis. Fecaliths, hyperplastic lymphoid follicles, foreign bodies, or tumors may cause the obstruction. Right lower quadrant abdominal pain, nausea, vomiting, diarrhea, and fever are the typical manifestations of acute appendicitis.

Exam 10: Pathology

Rats exposed to high concentrations of carbon tetrachloride suffer rapid and extensive liver damage. Light microscopic examination of affected liver specimens shows fatty change and hepatocyte necrosis. These changes are the result of:

A 5-month-old boy is being evaluated for poor weight gain since birth. He is noted to have bulky and greasy stools. A jejunal biopsy shows the findings seen in the slide below. Which of the following is the most likely diagnosis?

A 32-year-old man with mild abdominal discomfort and anorexia admits consuming large amounts of alcohol recently. He undergoes a liver biopsy, which shows the light microscopy findings seen in the image below. Which of the following is the most likely cause of this patient's condition?