Gastrointestinal and Liver PathologyKristine Krafts, M.D. | October 15-16, 2012
GI Pathology Outline
• Esophagus• Stomach• Intestine• Liver• Gallbladder• Pancreas
GI Pathology Outline
• Esophagus• Hiatal hernia• Mallory-Weiss syndrome• Barrett esophagus• Carcinoma
Normal esophageal-gastric junction
• Dilated portion of stomach protrudes above diaphragm
• Common! Usually asymptomatic.
• Heartburn, reflux esophagitis
• Danger: ulceration, bleeding
Hiatal Hernia
Sliding (L) and rolling (R) hiatal hernias
• GE junction tears
• Severe vomiting (chronic alcoholics)
• Symptoms: bleeding, pain, infection
• Treatment: balloon tamponade
• Prognosis: usually heals; sometimes fatal
Mallory-Weiss Syndrome
Mallory-Weiss tears
Mallory-Weiss tears
• 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
Normal esophagus (L) and Barrett esophagus (R)
Barrett esophagus
Barrett esophagus
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
Adenocarcinoma of esophagus
Squamous cell carcinoma of esophagus
GI Pathology Outline
• Esophagus• Stomach• Gastritis• Ulcers• Carcinoma
• Chronic mucosal inflammation
• Symptoms: asymptomatic, or discomfort
• Cause: Helicobacter pylori, autoimmune gastritis
• Danger: intestinal metaplasia
Gastritis
Chronic gastritis
Chronic gastritis
Helicobacter pylori organisms
Barry Marshall and Robin Warren
www.giantmicrobes.com
ulcer plush doll: $5.95
cytokinesfree
radicals
holes
immobilized T-helper
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What happens after infection?
Helicobacter infection
Asymptomatic gastritis
UlcerSymptomatic gastritis
Carcinoma Lymphoma
• Acute mucosal inflammation (usually transitory)
• Causes include: NSAIDS, alcohol, smoking
• Superficial or full-thickness
• Can lead to erosions
• Asymptomatic or pain, vomiting, hematemesis
Gastritis
• Erosion of mucosa into submucosa
• Causes: H. pylori, NSAIDs
• Symptoms: epigastric pain
• Danger: bleeding, perforation
Ulcer
• 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?
Ulcer
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
Intestinal-type gastric carcinoma: glands
Diffuse gastric carcinoma: signet ring cells
Signet ring cell
Gastric carcinoma presenting as mass
Gastric carcinoma presenting as ulcer
Gastric carcinoma presenting as linitis plastica
GI Pathology Outline
• Esophagus• Stomach• Intestine• Diverticulosis• Inflammatory bowel disease• Carcinoma
• Mucosa/submucosa herniates through muscle wall
• Older patients, low fiber diet
• Sigmoid colon
• Asymptomatic unless infected (“diverticulitis”)
Diverticulosis
Diverticulosis
Diverticulosis
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
Crohn disease Ulcerative colitis
• Common! 50% of people >60.
• Benign glands; may become dysplastic
• More dangerous when:• Large (>1 cm)• Villous architecture• Severely dysplastic
Adenoma
Tubular adenoma of colon
Villous adenoma of colon
Dysplastic (L) vs. normal (R) epithelium
• 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
Colon carcinoma
Colon carcinoma
GI Pathology Outline
• Esophagus• Stomach• Intestine• Liver• Hepatitis• Alcoholic liver disease• Hemochromatosis• Wilson disease• Carcinoma
• 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
A - picornavirus
B - hepadnavirus
C - flavivirus
D - defective virus
E - calcivirus
Physically
Handicapped
Fellow
Died
Cycling
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
Hepatitis B outcomes
Hepatitis C outcomes
Acute viral hepatitis
Chronic viral hepatitis
Chronic viral hepatitis: ground-glass hepatocytes
• 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
Bilirubin metabolism
and elimination
Jaundice
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
• Fibrotic, nodular liver
• Causes: alcoholism, hepatitis
• Leads to portal hypertension and liver failure
• Increased risk of liver carcinoma
Cirrhosis
Cirrhosis
Cirrhosis
• Decreased blood flow through liver
• Biggest cause: cirrhosis
• Symptoms• ascites• venous shunts (varices, hemorrhoids)• congestive splenomegaly• hepatic encephalopathy
Portal Hypertension
Consequences of portal hypertension
Esophageal varices
Caput medusae
• 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
• Hematomas, gingival bleeding
• Jaundiced mucosa
• Glossitis (in alcoholic hepatitis)
• Reduced healing after surgery
Oral Manifestations of Liver Injury
• 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
More youth with irreversible liver disease now
Alcoholic liver disease
Alcoholic steatosis
Alcoholic hepatitis: inflammation and Mallory bodies
Alcoholic cirrhosis
• 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
• 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
Skin bronzing in hemochromatosis
• 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
Kayser-Fleischer Rings
• 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
Hepatocellular carcinoma
Hepatocellular carcinoma
• Most common malignancy in the liver
• Usually multiple lesions
• Most common primaries: colon, lung, breast, pancreas, stomach.
Metastatic Carcinoma
Metastatic carcinoma
GI Pathology Outline
• Esophagus• Stomach• Intestine• Liver• Gallbladder• Cholelithiasis• Cholecystitis
• 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
Cholesterol gallstones
Pigmented gallstones
GI Pathology Outline
• Esophagus• Stomach• Intestine• Liver• Gallbladder• Pancreas• Pancreatitis• Carcinoma
• Exocrine pancreas• Makes enzymes for digestion• Diseases: Pancreatitis, cystic fibrosis, tumors
• Endocrine pancreas• Makes insulin, glucagon, other hormones• Diseases: Diabetes, tumors
Normal Pancreas
• 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
Cell injury(alcohol)
Obstruction(gallstones)
• 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
• 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
Pancreatic carcinoma
Pancreatic carcinoma
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