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Gastrointestinal and Liver Pathology

Kristine 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

Hiatal Hernia

Dilated portion of stomach protrudes

above diaphragm
Common! Usually asymptomatic.
Heartburn, reflux esophagitis Danger: ulceration, bleeding

Sliding (L) and rolling (R) hiatal hernias

Mallory-Weiss Syndrome
GE junction tears Severe vomiting (chronic alcoholics)

Symptoms: bleeding, pain, infection


Treatment: balloon tamponade Prognosis: usually heals; sometimes fatal

Mallory-Weiss tears

Mallory-Weiss tears

Barrett Esophagus

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

Normal esophagus (L) and Barrett esophagus (R)

Barrett esophagus

Barrett esophagus

Esophageal Carcinoma
Adenocarcinoma
Commonest type in US Risk factor: Barrett

Squamous cell carcinoma


Commonest type worldwide Risk factors: esophagitis,

esophagus
Distal 1/3 of esophagus Symptoms: insidious onset;

smoking, alcohol, genetics


Middle 1/3 of esophagus Symptoms: insidious onset;

late obstruction

late obstruction

Adenocarcinoma of esophagus

Squamous cell carcinoma of esophagus

GI Pathology Outline
Esophagus Stomach Gastritis Ulcers Carcinoma

Gastritis

Chronic mucosal inflammation Symptoms: asymptomatic, or discomfort Cause: Helicobacter pylori, autoimmune gastritis Danger: intestinal metaplasia

Chronic gastritis

Chronic gastritis

Helicobacter pylori organisms

Barry Marshall and Robin Warren

ulcer plush doll: $5.95


www.giantmicrobes.com

holes free radicals cytokines immobilized T-helper cells

What happens after infection?


Helicobacter infection

Asymptomatic gastritis

Symptomatic Ulcer gastritis

Carcinoma Lymphoma

Gastritis
Acute mucosal inflammation (usually transitory)
Causes include: NSAIDS, alcohol, smoking Superficial or full-thickness Can lead to erosions Asymptomatic or pain, vomiting, hematemesis

Ulcer

Erosion of mucosa into submucosa Causes: H. pylori, NSAIDs Symptoms: epigastric pain Danger: bleeding, perforation

How does Helicobacter cause ulcers?


Bugs hide in mucous
and attract inflammatory cells

Inflammatory cells
release toxins but cant kill bugs easily

Host causes damage


by continual, ineffective immune response!

Ulcer

Gastric Carcinoma
Intestinal type
Arises in intestinal
metaplasia

Diffuse type
Arises from gastric glands Risk factors undefined

Risk factors: chronic


gastritis, bad diet

Signet ring morphology


Generally asymptomatic

Glandular morphology
Generally asymptomatic

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

Diverticulosis
Mucosa/submucosa herniates through

muscle wall
Older patients, low fiber diet Sigmoid colon Asymptomatic unless infected

(diverticulitis)

Diverticulosis

Diverticulosis

Inflammatory Bowel Disease


Crohn Disease
Anywhere Patchy Transmural Poor response to surgery

Ulcerative Colitis
Colon only Continuous Superficial Good response to surgery

Increased risk of cancer

Increased risk of cancer

Crohn disease

Ulcerative colitis

Adenoma

Common! 50% of people >60. Benign glands; may become dysplastic

More dangerous when:


Large (>1 cm) Villous architecture Severely dysplastic

Tubular adenoma of colon

Villous adenoma of colon

Dysplastic (L) vs. normal (R) epithelium

Colon Carcinoma
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

GI Pathology Outline
Esophagus Stomach Intestine

Liver
Hepatitis Alcoholic liver disease

Hemochromatosis
Wilson disease Carcinoma

Viral Hepatitis

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)

A - picornavirus
B - hepadnavirus C - flavivirus D - defective virus E - calcivirus

Physically
Handicapped Fellow Died Cycling

Hepatitis A Transmission Chronic Hepatitis Fulminant hepatitis Carcinoma Other stuff Bottom line Fecal-oral None

Hepatitis B Parenteral 5%

Hepatitis C Parenteral >85%

0.1%
No 50% of people > 50 are + Benign, selflimited disease

0.1-1.0%
Yes

Rare
Yes

Most common Vaccine reason for liver effective transplant Most recover; Nasty! Almost small % die 10% die

Hepatitis B outcomes

Hepatitis C outcomes

Acute viral hepatitis

Chronic viral hepatitis

Chronic viral hepatitis: ground-glass hepatocytes

Jaundice
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)

Bilirubin metabolism and elimination

Jaundice

Laboratory Tests
Serum aspartate aminotransferase (AST)

Hepatocyte integrity
Serum alanine aminotransferase (ALT) Serum bilirubin (total and direct)

Biliary function
Serum alkaline phosphatase Serum albumin

Hepatocyte function
Prothrombin time

Cirrhosis

Fibrotic, nodular liver Causes: alcoholism, hepatitis Leads to portal hypertension and liver failure Increased risk of liver carcinoma

Cirrhosis

Cirrhosis

Portal Hypertension
Decreased blood flow through liver Biggest cause: cirrhosis Symptoms ascites

venous shunts (varices, hemorrhoids)


congestive splenomegaly hepatic encephalopathy

Consequences of portal hypertension

Esophageal varices

Caput medusae

Liver Failure
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

Oral Manifestations of Liver Injury

Hematomas, gingival bleeding Jaundiced mucosa Glossitis (in alcoholic hepatitis) Reduced healing after surgery

Alcoholic Liver Disease


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

More youth with irreversible liver disease now

Alcoholic liver disease

Alcoholic steatosis

Alcoholic hepatitis: inflammation and Mallory bodies

Alcoholic cirrhosis

Alcoholic Liver Disease


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

Hereditary hemochromatosis
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

Skin bronzing in hemochromatosis

Wilson Disease
Autosomal recessive disease: body copper
Cause: mutation in gene regulating copper

excretion
Symptoms: acute and chronic liver disease,

neuropsychiatric manifestations, KayserFleisher rings in cornea


Treatment: copper chelation therapy

Kayser-Fleischer Rings

Hepatocellular Carcinoma
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

Metastatic Carcinoma

Most common malignancy in the liver Usually multiple lesions Most common primaries: colon, lung,

breast, pancreas, stomach.

Metastatic carcinoma

GI Pathology Outline
Esophagus Stomach Intestine

Liver
Gallbladder Cholelithiasis

Cholecystitis

Cholelithiasis
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

Cholesterol gallstones

Pigmented gallstones

GI Pathology Outline
Esophagus Stomach Intestine

Liver
Gallbladder Pancreas

Pancreatitis
Carcinoma

Normal Pancreas
Exocrine pancreas Makes enzymes for digestion Diseases: Pancreatitis, cystic fibrosis, tumors Endocrine pancreas Makes insulin, glucagon, other hormones Diseases: Diabetes, tumors

Acute Pancreatitis
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

Obstruction (gallstones)

Cell injury (alcohol)

Chronic Pancreatitis

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)

Pancreatic Carcinoma

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

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