Compare and contrast the clinical and pathologic findings with ulcerative colitis and Crohn's disease. (<250 words)

Both ulcerative colitis (UC) and Crohn's disease are inflammatory bowel diseases (IBD's) seen more frequently at a younger age (20's), in whites, in females, and within families. Clinically, both can have exacerbations and remissions. There may be diarrhea (bloody with UC) and abdominal pain (more severe with Crohn's). In 10 to 20% of cases, they cannot be easily distinguished. Extraintestinal manifestations of IBD can include migratory polyarthritis, sacroilitis, erythema nodosum, and biliary tract disease.

Pathologically, UC has mucosal and submucosal involvement, beginning in and virtually always involving the rectum, then involving remaining portions of colon in a continuous fashion. A "backwash" ileitis may occur, but no other parts of the GI tract are involved. In severe exacerbations, ulceration can leave only islands of remaining mucosa -- pseudopolyps -- or a toxic megacolon can ensue. Microscopically, the glands show acute and chronic inflammation with loss of goblet cells and crypt abscesses. Colectomy is curative of UC and also is prophylaxis against the common long-term complication of adenocarcinoma.

Crohn's disease can affect any portion of the GI tract, but is most often seen in ileum and colon. Small intestinal involvement can lead to malabsorption with B12 deficiency and disrupted enterohepatic circulation of bile salts. Distribution of the disease is segmental. Involved portions show transmural inflammation, possibly with granulomas. This leads to fissures, fistulae, and adhesions that may required surgical intervention, but this is not curative, as Crohn's can recur in remaining bowel. Adenocarcinoma can occur, but not as often as with UC.

Discuss the clinical, laboratory, and pathologic features of gastric adenocarcinoma. (<250 words)

Gastric adenocarcinoma has been decreasing in incidence in the U.S. for the past 50 years, but it is still common in some places (Japan). Patients may present with epigastric pain, hematemesis, weight loss, and early satiety. Risk factors include blood group A, presence of chronic atrophic gastritis (some with pernicious anemia), adenomatous polyps, smoking, and diet that includes pickled or smoked foods.

Since there are no good early signs and symptoms, few of these lesions in the U.S. are early gastric carcinomas which have not invaded the muscularis and which have a >90% 5-year survival. Instead, most gastric cancers are found at a more extensive stage and the 5-year survival in the U.S. is only about 10%. Grossly, these cancers have two main forms. An exophytic type seen with intestinal metaplasia that microscopically has a glandular configuration with mucin-secreting neoplastic cells. This type occurs more in males and has been decreasing in incidence. A diffuse infiltrative type extensively infiltrates the gastric wall, leading to a linitis plastica pattern with neoplastic signet ring cells that infiltrate singly.

Any of the various types of gastric adenocarcinomas may produce ulcerations, not always distinguishable from benign peptic ulcers, and endoscopic biopsy is essential for diagnosis. These cancers spread most often to surrounding organs or to lymph nodes.

Discuss the clinical and pathologic findings in the GI tract in a patient with viral hepatitis. (<250 words)

(Example 1)

Viral hepatitis may be caused by many different entities, including the hepatitis A, B, C, D, E, and F viruses and Epstein-Barr viruses in healthy children and adults, cytomegalovirus in neonates or immunocompromised patients, and herpes simplex virus in immunocompromised patients. These viruses produce an acute hepatitis more commonly. Some viruses such as HBV and HCV can progress to chronic hepatitis.

Acute viral hepatitis most commonly presents with a history of viral prodrome--low grade fever, malaise, myalgias--followed by other symptoms which may include jaundice, dark urine, and acholic stools. Often the patient does not feel very sick and may be asymptomatic. Laboratory tests would reveal atypical lymphocytes, elevated bilirubin, greatly elevated AST and ALT, slightly elevated alkaline phosphatase, normal albumin, and a normal or prolonged prothrombin time. Pathologically, the liver would show mononuclear inflammation of hepatic lobules and portal tracts with ballooning degeneration and necrosis of hepatocytes.

Chronic viral hepatitis is seen most often with HBV and HCV. With HCV infection the acute phase is often asymptomatic and the disease presents as chronic hepatitis. Clinical symptoms are often similar to acute hepatitis, with jaundice, dark urine, pruritis, and acholic stools. Laboratory studies show an elevated bilirubin, moderately elevated AST and ALT, decreased albumin, and often a prolonged protime. Pathologically, the liver can show either chronic persistent or chronic active hepatitis. Chronic persistent hepatitis involves only portal triads. In chronic active hepatitis, the inflammation involves adjacent hepatocytes, causing a "piecemeal necrosis." Chronic active hepatitis can progress to macronodular cirrhosis with risk for hepatocellular carcinoma.

Discuss the clinical and pathologic findings in the GI tract in a patient with viral hepatitis. (<250 words)

(Example 2)

Hepatitis can be caused by a number of different viruses. Acute viral hepatitis is often due to hepatitis viruses A and B, and occasionally C (HAV, HBV, HCV). With HAV, the infection is only acute and self-limited; this is also often the case with HBV, but HBV can proceed to a chronic hepatitis as well. HCV often presents as a chronic hepatitis, as the acute infection is often subclinical and a majority of HCV infections progress to chronic hepatitis.

Serology is the most helpful laboratory test in diagnosing viral hepatitis and in distinguishing among the possible causes. Anti-HAV-IgM is indicative of acute HAV hepatitis. HBsAg and anti-HBc-IgM are indicative of acute HBV infection, whereas anti-HBs or anti-HBc-IgG in the presence of jaundice or other symptoms of hepatitis would point to a chronic or past HBV infection. Similarly, anti-HCV-IgM implies acute HCV infection, while anti-HCV-IgG suggests a chronic process.

Microscopically or grossly, the viral hepatitises all appear similarly if they are in a corresponding stage of progression. With acute viral hepatitis, edematous hepatic lobules and a lymphoplasmacytic infiltrate could be seen. If the infection progressed to a chronic active hepatitis, piecemeal necrosis might be observed as well as bridging necrosis and fibrosis. Long-standing infection results in cirrhosis characterized microscopically by fibrous septae between portal tracts that divide the regenerating parenchyma into nodules, usually macronodular and larger than 0.5 cm.

Discuss the clinical and pathologic findings in the GI tract in a patient with viral hepatitis. (<250 words)

(Example 3)

Viral hepatitis can be caused by hepatitis viruses A, B, C, D, E, and F. In some instances CMV and EBV can cause hepatitis, but usually in immunosuppressed patients such as newborns or those with AIDS. In the United States, the most common are the hepatitis viruses A - D, with B being the most severe. HAV is transmitted by the fecal-oral route and only exists in the acute form. HBV is transmitted by blood, sexual contact, and vertically through placenta. About 20% of HBV cases will become chronic, with younger patients at increased risk. This chronic state can be as a carrier/transmitter only or it can be in a chronic active state with continually worsening liver pathology. HCV is transmitted by blood, usually with intravenous drug use, though transfusion used to be common. About 50% of these will go on to a chronic state similar to HBV. HDV infection can only occur along with HBV and has the same pattern of transmission.

Acute hepatitis will usually present with jaundice, malaise, markedly increased liver enzymes (AST and ALT), and possibly an increase in alkaline phosphatase. Biopsy may reveal hepatocyte swelling and necrosis and multinucleated hepatocytes. There would also likely be portal mononuclear inflammation and cholestasis.

Chronic hepatitis, due to the same processes as acute, has continued necrosis with fibrosis. Regenerative nodules may form. This process continues with declining liver function and cirrhosis. With decreased liver function and cirrhosis (usually macronodular), extrahepatic manifestations may occur such as portal hypertension, ascites, and hepatic encephalopathy.

Discuss the clinical and pathologic findings in the GI tract in a patient with viral hepatitis. (<250 words)

(Example 4)

There are several different types of viruses that can lead to hepatitis. They are both RNA and DNA viruses; each virus has its own spectrum of detrimental effects. A list of the viruses is as follows:

Hepatitis A - this is an RNA virus that is transmitted by the fecal-oral route. It causes an acute hepatitis with almost no chance of progression to chronic hepatitis. Treatment is with immunoglobulins.

Hepatitis B - this is a DNA virus that is spread by contact with infected blood and/or sexual contact. It is also spread from mother to fetus during birth. The virus causes an acute hepatitis, with a greater probability of becoming chronic. It is also associted with high morbidity from cirrhosis and an increased risk for hepatocellular carcinoma. Immunization is recommended to prevent it.

Hepatitis C - this RNA virus is spread by blood and/or sexual contact. It carries the greatest risk for chronic hepatitis.

Hepatitis D - this RNA virus is seen only with hepatitis B because it requires the presence of hepatitis B for replication. It is spread in the same manner as hepatitis B and causes chronic hepatitis.

Hepatitis E - this RNA virus is spread by the fecal-oral route and is quite rare.

These viruses can cause liver disease, hyperbilirubinemia, cirrhosis and its complications, and can be very serious diseases for the patient.

Discuss the clinical and pathologic findings in the GI tract in a patient with diarrhea. (<250 words)

(Example 1)

The normal volume of stool is about 150cc/day, at a frequency of 3/day to 3/week. Diarrhea is an increased volume of stool (>200cc/day) or increased frequency (>3/day). Large volume, watery stools usually arise from a disease involving the small intestine, whereas small volume, very frequent stools with tenesmus usually arise from a disease in the colon.

Diarrhea may be due to increased fluid secretion in the the bowel due to infections such as V. cholera, E. coli, or Salmonella. Diarrhea may be due to decreased absorption due to a variety of reasons such as: a) infection with Yersinia or Shigella, b) pseudomembranous colitis due to C. dificile, c) ulcerative colitis or Crohn's disease, d) increased osmolality of the lumenal contents due to increased fat, bile acids, or disaccharides, e) shortened bowel due to surgical removal or fistula.

Increased fat, bile acids, and disaccharides in the colon are due to pancreatic enzyme deficiency (possibly secondary to obstruction), terminal ileal disease, or lactase deficiency, respectively. Diarrhea may simply be caused by laxative abuse. Diagnosis and treatment would depend mainly on history and stool examination, including culture. The most important aspect of treatment is fluid and electrolyte replacement.

Discuss the clinical and pathologic findings in the GI tract in a patient with diarrhea. (<250 words)

(Example 2)

Diarrhea, the passage of frequent, loose stools, is caused by anything which inhibits absorption and/or enhances secretion of fluid and electrolytes into the bowel lumen. There are many causes of diarrhea.

Organisms which cause diarrhea include E. coli, Salmonella, Shigella, rotavirus (in children), Norwalk virus, and others. Of particular interest is pseudomembranous colitis caused by overgrowth of Clostridium difficile. The gross appearance of colon would show a hyperemic mucosa with the exudation of yellow-green pseudomembranes which appear plaque-like. These are composed of necrotic material and a primarily PMN exudate. The usual cause is treatment with broad spectrum antibiotics with destruction of the normal flora, allowing C. dificile overgrowth.

Withe the rise of acquired immunodeficiency syndrome cases, an organism which is not a usual pathogen can cause intractable diarrhea -- cryptosporidium. It produces a watery diarrhea that is quite crippling in the patient.

An interesting disease both clinically and pathologically is gluten enteropathy (sprue or celiac disease). An epithelial allergic reaction to the wheat protein gluten causes destruction of the intestinal mucosa with flattening of the villi. This causes a marked reduction in the absorptive ability of the mucosa with malabsorption with diarrhea. Diagnosis is made by recognizing the flattened mucosa on small intestinal biopsy with a return to normal configuration on a gluten-free diet.

Discuss the clinical and pathologic findings in the GI tract in a patient with diarrhea. (<250 words)

(Example 3)

Diarrhea is an increase in solutes and fluid in the GI tract lumen manifesting clinically as increased stool volumes, usually >200cc/day. Classification is small or large volume: small=colon and large=small intestine.

There are many etiologies for diarrhea, such as infectious, inflammatory, increased motility (i.e., decreased transit time), decreased absorptive surface (small bowel resection or ileostomy or decreased functional surface area with celiac sprue), lack of enzymes (either exocrine or brush border), and bile salt (depletion of body pool or lack of a terminal ileum) to name some. Two etiologies are discussed.

Infectious diarrhea can present with blood, PMN's, and bacteria in the stool if invasive -- i.e., Shigella, Salmonella typhi, and invasive E. coli -- or with extremely large volumes of stool secondary to enterotoxins that increase secretion, as with Vibrio cholerae. Viruses such as rotavirus or Norwalk agents are seen in children during winter months in northern climates. Giardia will present as a watery, non-invasive diarrhea with cysts sometimes seen in stool or with a duodenal aspirate, while E. histolytica will present with an invasive, bloody diarrhea.

Celiac sprue secondary to mucosal damage from gluten sensitivity will show atrophic, flattened villi, reversible with a gluten-free diet. The diarrhea is an osmotic as well as mucosal problem as the brush border enzymes and uptake receptors are depleted along with greatly reduced absorptive surface.

Answer by drawing a diagram and explaining in a short paragraph your five favorite hepatic lesions. (<250 words)

There are quite a few hepatic lesions that could be discussed. Here are several:

Macronodular cirrhosis: Viral hepatitis B or viral hepatitis C can, in a chronic form, lead to the appearance of hepatocyte necrosis followed by periportal fibrosis and regeneration. The regenerative nodules are typically >3 mm in size. Cirrhosis leads to portal hypertension. Hypoalbuminemia and coagulopathies from decreased protein synthesis are common

Micronodular cirrhosis: This is most often due to chronic alcoholism. The hepatic injury with necrosis leads to periportal fibrosis and regeneration of hepatocytes in a nodular fashion. The nodules are usually <3 mm in size. Complications of the resultant portal hypertension can include esophageal varices, congestive splenomegaly, and ascites.

Alcoholic hepatitis: The acute liver injury from binge drinking leads to extensive hepatocyte necrosis with fibrosis and acute inflammation. Hepatocytes contain abundant Mallory's alcoholic hyaline (aggregated intermediate filaments). Fatty change is prominent.

Chronic active hepatitis: Most often with hepatitis B or hepatitis C viruses, and almost never with hepatitis A, there can be a continuing infection with destruction of liver lobules. There is "piecemeal" necrosis around the edges of the lobules with extension of chronic inflammatory cells with hepatocyte necrosis into surrounding parenchyma. ALT and AST enzymes continue to be elevated.

Hepatocellular carcinoma: Usually in the background of cirrhosis, hepatocellular carcinoma can arise as a mass lesion, sometimes multifocal, in the liver. The neoplastic hepatocytes often produce alpha-fetoprotein that can be detected in the serum. Necrosis, capsular rupture, and hemoperitoneum are complications.

Hepatic adenoma: This is rare, but most often seen in young women taking oral contraceptives. The adenoma is composed of normal appearing hepatocytes without the usual portal structure or central vein architecture. The mass is usually small.

Fatty liver: Nutritional fatty change is most often due to chronic alcoholism, but can also appear with malabsorption, obesity, diabetes mellitus, or poor diet. Lipoprotein transport is impaired and lipid builds up in hepatocytes and appears as a fatty vacuole.

Chronic passive congestion: With right-sided congestive heart failure, there is increased congestion within the hepatic sinusoids, beginning around the central vein. The liver has a "nutmeg" appearance grossly. If severe, there may be centrilobular necrosis of hepatocytes. If chronic, there may even be fibrosis.

Extrahepatic biliary tract obstruction: Gallstones or neoplasms (such as adenocarcinoma of the head of the pancreas) may obstruct the common bile duct and lead to cholestasis. The direct bilirubin is increased the most, and an increased alkaline phosphatase also suggests extrahepatic obstruction. The patient is icteric.

Metastatic carcinoma: The liver is a common site for metastatic disease, particularly from primary sites in the gastrointestinal tract such as colon, stomach, and pancreas. Usually, multiple nodules of varying size are present which may cause local obstruction to increase the alkaline phosphatase, but not bilirubin.