gastrointestinal and liver pathology

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

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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