Gastrointestinal and Liver Pathology
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Transcript of Gastrointestinal and Liver Pathology
![Page 1: Gastrointestinal and Liver Pathology](https://reader033.fdocuments.us/reader033/viewer/2022061423/55cf9ba3550346d033a6d4f3/html5/thumbnails/1.jpg)
Gastrointestinal and Liver PathologyKristine Krafts, M.D. | October 15-16, 2012
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GI Pathology Outline
• Esophagus• Stomach• Intestine• Liver• Gallbladder• Pancreas
![Page 3: Gastrointestinal and Liver Pathology](https://reader033.fdocuments.us/reader033/viewer/2022061423/55cf9ba3550346d033a6d4f3/html5/thumbnails/3.jpg)
GI Pathology Outline
• Esophagus• Hiatal hernia• Mallory-Weiss syndrome• Barrett esophagus• Carcinoma
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Normal esophageal-gastric junction
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• Dilated portion of stomach protrudes above diaphragm
• Common! Usually asymptomatic.
• Heartburn, reflux esophagitis
• Danger: ulceration, bleeding
Hiatal Hernia
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Sliding (L) and rolling (R) hiatal hernias
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• GE junction tears
• Severe vomiting (chronic alcoholics)
• Symptoms: bleeding, pain, infection
• Treatment: balloon tamponade
• Prognosis: usually heals; sometimes fatal
Mallory-Weiss Syndrome
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Mallory-Weiss tears
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Mallory-Weiss tears
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• Replacement of squamous epithelium by columnar epithelium with goblet cells
• Complication of long-standing reflux esophagitis
• Danger: 30-100x risk of adenocarcinoma
• Treatment: screen for high-grade dysplasia
Barrett Esophagus
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Normal esophagus (L) and Barrett esophagus (R)
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Barrett esophagus
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Barrett esophagus
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Adenocarcinoma• Commonest type in US
• Risk factor: Barrett esophagus
• Distal 1/3 of esophagus
• Symptoms: insidious onset; late obstruction
Squamous cell carcinoma• Commonest type worldwide
• Risk factors: esophagitis, smoking, alcohol, genetics
• Middle 1/3 of esophagus
• Symptoms: insidious onset; late obstruction
Esophageal Carcinoma
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Adenocarcinoma of esophagus
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Squamous cell carcinoma of esophagus
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GI Pathology Outline
• Esophagus• Stomach• Gastritis• Ulcers• Carcinoma
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• Chronic mucosal inflammation
• Symptoms: asymptomatic, or discomfort
• Cause: Helicobacter pylori, autoimmune gastritis
• Danger: intestinal metaplasia
Gastritis
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Chronic gastritis
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Chronic gastritis
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Helicobacter pylori organisms
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Barry Marshall and Robin Warren
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www.giantmicrobes.com
ulcer plush doll: $5.95
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cytokinesfree
radicals
holes
immobilized T-helper
cells
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What happens after infection?
Helicobacter infection
Asymptomatic gastritis
UlcerSymptomatic gastritis
Carcinoma Lymphoma
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• Acute mucosal inflammation (usually transitory)
• Causes include: NSAIDS, alcohol, smoking
• Superficial or full-thickness
• Can lead to erosions
• Asymptomatic or pain, vomiting, hematemesis
Gastritis
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• Erosion of mucosa into submucosa
• Causes: H. pylori, NSAIDs
• Symptoms: epigastric pain
• Danger: bleeding, perforation
Ulcer
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• Bugs hide in mucous and attract inflammatory cells
• Inflammatory cells release toxins but can’t kill bugs easily
• Host causes damage by continual, ineffective immune response!
How does Helicobacter cause ulcers?
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Ulcer
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Intestinal type
• Arises in intestinal metaplasia
• Risk factors: chronic gastritis, bad diet
• Glandular morphology
• Generally asymptomatic
Diffuse type• Arises from gastric glands
• Risk factors undefined
• Signet ring morphology
• Generally asymptomatic
Gastric Carcinoma
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Intestinal-type gastric carcinoma: glands
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Diffuse gastric carcinoma: signet ring cells
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Signet ring cell
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Gastric carcinoma presenting as mass
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Gastric carcinoma presenting as ulcer
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Gastric carcinoma presenting as linitis plastica
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GI Pathology Outline
• Esophagus• Stomach• Intestine• Diverticulosis• Inflammatory bowel disease• Carcinoma
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• Mucosa/submucosa herniates through muscle wall
• Older patients, low fiber diet
• Sigmoid colon
• Asymptomatic unless infected (“diverticulitis”)
Diverticulosis
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Diverticulosis
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Diverticulosis
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Crohn Disease• Anywhere
• Patchy
• Transmural
• Poor response to surgery
• Increased risk of cancer
Ulcerative Colitis• Colon only
• Continuous
• Superficial
• Good response to surgery
• Increased risk of cancer
Inflammatory Bowel Disease
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Crohn disease Ulcerative colitis
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• Common! 50% of people >60.
• Benign glands; may become dysplastic
• More dangerous when:• Large (>1 cm)• Villous architecture• Severely dysplastic
Adenoma
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Tubular adenoma of colon
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Villous adenoma of colon
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Dysplastic (L) vs. normal (R) epithelium
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• Almost always arises in adenomatous polyp
• Diet: low fiber, high fat, lots of refined carbs
• Symptoms: • silent for years• fatigue, weakness, iron-deficiency anemia• occult bleeding, crampy pain
• 5 year prognosis: 4% (stage 4) - 90% (stage 1)
Colon Carcinoma
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Colon carcinoma
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Colon carcinoma
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GI Pathology Outline
• Esophagus• Stomach• Intestine• Liver• Hepatitis• Alcoholic liver disease• Hemochromatosis• Wilson disease• Carcinoma
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• Caused by Hepatitis A, B, or C viruses
• Some cases asymptomatic
• Some cases symptomatic:• Acute (jaundice)• Chronic (may lead to cirrhosis and liver failure)• Fulminant (liver failure)
Viral Hepatitis
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A - picornavirus
B - hepadnavirus
C - flavivirus
D - defective virus
E - calcivirus
Physically
Handicapped
Fellow
Died
Cycling
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Hepatitis A Hepatitis B Hepatitis C
Transmission Fecal-oral Parenteral Parenteral
ChronicHepatitis None 5% >85%
Fulminanthepatitis 0.1% 0.1-1.0% Rare
Carcinoma No Yes Yes
Other stuff 50% of people > 50 are +
Vaccine effective
Most common reason for liver
transplant
Bottom line Benign, self-limited disease
Most recover;small % die
Nasty! Almost 10% die
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Hepatitis B outcomes
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Hepatitis C outcomes
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Acute viral hepatitis
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Chronic viral hepatitis
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Chronic viral hepatitis: ground-glass hepatocytes
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• Yellow skin, eyes due to elevated bilirubin
• Conjugated hyperbilirubinemia• liver excretion (hepatitis)• bile flow (tumor blocking bile duct)
• Unconjugated hyperbilirubinemia• production (hemolytic anemia)• uptake (hepatitis)
Jaundice
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Bilirubin metabolism
and elimination
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Jaundice
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Laboratory Tests
Hepatocyte integritySerum aspartate aminotransferase (AST)
Serum alanine aminotransferase (ALT)
Biliary functionSerum bilirubin (total and direct)
Serum alkaline phosphatase
Hepatocyte functionSerum albumin
Prothrombin time
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• Fibrotic, nodular liver
• Causes: alcoholism, hepatitis
• Leads to portal hypertension and liver failure
• Increased risk of liver carcinoma
Cirrhosis
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Cirrhosis
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Cirrhosis
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• Decreased blood flow through liver
• Biggest cause: cirrhosis
• Symptoms• ascites• venous shunts (varices, hemorrhoids)• congestive splenomegaly• hepatic encephalopathy
Portal Hypertension
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Consequences of portal hypertension
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Esophageal varices
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Caput medusae
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• End point of severe liver disease
• Causes: fulminant hepatitis, cirrhosis, drug overdose
• Symptoms: jaundice, edema, bleeding, hyperammonemia
• Multiple organ-system failure• Hepatic encephalopathy• Hepatorenal syndrome
Liver Failure
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• Hematomas, gingival bleeding
• Jaundiced mucosa
• Glossitis (in alcoholic hepatitis)
• Reduced healing after surgery
Oral Manifestations of Liver Injury
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• 100,000 -200,000 deaths/year
• Effects on liver: steatosis, hepatitis, cirrhosis
• How much do you need to drink?• Short-term ingestion of 8 beers/day
reversible steatosis• Long-term ingestion of 5 beers/day
severe injury
• Beer and binge drinking are risky
Alcoholic Liver Disease
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More youth with irreversible liver disease now
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Alcoholic liver disease
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Alcoholic steatosis
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Alcoholic hepatitis: inflammation and Mallory bodies
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Alcoholic cirrhosis
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• Abstinence: 5ys is 90%
• Continued drinking: 5ys drops to 50-60%
• Causes of death in end-stage alcoholism:• Liver failure• Massive GI bleed• Infection• Hepatorenal syndrome• Hepatocellular carcinoma
Alcoholic Liver Disease
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• Autosomal recessive disease: body iron
• Cause: mutations in hemochromatosis gene (regulates iron absorption)
• Cirrhosis, skin pigmentation, liver carcinoma
• Early detection and treatment (phlebotomy, iron chelators) = normal life expectancy
Hereditary hemochromatosis
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Skin bronzing in hemochromatosis
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• Autosomal recessive disease: body copper
• Cause: mutation in gene regulating copper excretion
• Symptoms: acute and chronic liver disease, neuropsychiatric manifestations, Kayser-Fleisher rings in cornea
• Treatment: copper chelation therapy
Wilson Disease
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Kayser-Fleischer Rings
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• Strongly associated with hepatitis B and C, chronic liver disease, and aflatoxins
• Rapid increase in liver size, worsening ascites, fever and pain
• alpha fetoprotein level
• Median survival 7 months (death from bleeding, liver failure, cachexia)
Hepatocellular Carcinoma
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Hepatocellular carcinoma
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Hepatocellular carcinoma
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• Most common malignancy in the liver
• Usually multiple lesions
• Most common primaries: colon, lung, breast, pancreas, stomach.
Metastatic Carcinoma
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Metastatic carcinoma
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GI Pathology Outline
• Esophagus• Stomach• Intestine• Liver• Gallbladder• Cholelithiasis• Cholecystitis
![Page 89: Gastrointestinal and Liver Pathology](https://reader033.fdocuments.us/reader033/viewer/2022061423/55cf9ba3550346d033a6d4f3/html5/thumbnails/89.jpg)
• Common! (10% of adults in US)
• Cholesterol stones: Female, Fat, Fertile, Forty
• Pigment (bilirubin) stones: Asian countries, hemolytic anemia and biliary infections
• Symptoms: None, or excruciating pain
• Complications: cholecystitis, empyema, perforation, fistula, obstruction, pancreatitis
Cholelithiasis
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Cholesterol gallstones
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Pigmented gallstones
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GI Pathology Outline
• Esophagus• Stomach• Intestine• Liver• Gallbladder• Pancreas• Pancreatitis• Carcinoma
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• Exocrine pancreas• Makes enzymes for digestion• Diseases: Pancreatitis, cystic fibrosis, tumors
• Endocrine pancreas• Makes insulin, glucagon, other hormones• Diseases: Diabetes, tumors
Normal Pancreas
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• Acute inflammation and reversible destruction of pancreas
• Symptoms: abdominal pain radiating to back
• Main causes: alcoholism, gallstones
• Labs: elevated serum amylase and lipase
• Prognosis: Most recover, but 5% die in first week
Acute Pancreatitis
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Cell injury(alcohol)
Obstruction(gallstones)
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• Longstanding, irreversible pancreatic destruction
• Most are alcohol related, some idiopathic
• Symptoms: silent, or bouts of jaundice and pain
• Prognosis: poor (50% mortality over 20 years)
Chronic Pancreatitis
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• 4th leading cause of cancer death in US
• Biggest risk factor: smoking
• Highly invasive
• Silent until late; then pain, jaundice
• Very high mortality: 5ys <5%
Pancreatic Carcinoma
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Pancreatic carcinoma
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Pancreatic carcinoma