Transfusion Pathology

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Gastrointestinal and Liver Pathology
Kristine Krafts, M.D. October 27, 2009
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GI Pathology Outline

• Esophagus
• Stomach
• Intestine
• Liver
• Gallbladder
• Pancreas

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GI Pathology Outline

• Esophagus
• Achalasia
• Hiatal hernia
• Mallory-Weiss syndrome
• Varices
• Esophagitis
• Barrett esophagus
• Esophageal carcinoma

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Normal esophageal-gastric junction
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Achalasia

• Lower sphincter cant relax
• Result obstruction, dilatation
• Myenteric plexus ganglion cells ? or gone
• Symptoms dysphagia, regurgitation, aspiration
• Cause unknown
• Danger ? incidence squamous cell carcinoma

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Hiatal Hernia

• Dilated portion of stomach protrudes above
  diaphragm
• Sliding or rolling pattern
• Common! Usually asymptomatic.
• Heartburn, reflux esophagitis
• Danger ulceration, bleeding

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Sliding (L) and rolling (R) hiatal hernias
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Mallory-Weiss Syndrome

• GE junction tears
• Severe vomiting (chronic alcoholics)
• Symptoms bleeding, pain, infection
• Treatment balloon tamponade
• Prognosis usually heals sometimes fatal

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Mallory-Weiss tears
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Mallory-Weiss tears
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Esophageal Varices

• Dilated veins in lower esophagus
• Cause portal hypertension secondary to cirrhosis
• Asymptomatic (until rupture and massive bleed)
• Treatment sclerotherapy or ligation
• Prognosis 30 mortality during first episode
  most will recur within a year

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Esophageal varices
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Esophagitis

• Inflammation of esophageal lining
• Most cases in US due to reflux
• Cause sphincter malfunction, hiatal hernia
• Symptoms heartburn
• Danger bleeding, stricture, Barrett esophagus

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Barrett Esophagus

• Replacement of squamous epithelium by columnar
  epithelium with goblet cells
• Complication of long-standing reflux esophagitis
• Danger 30-100x increased risk of adenocarcinoma
• Treatment Periodically screen for high-grade
  dysplasia

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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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Esophageal Carcinoma

• Adenocarcinoma
• More common than squamous cell CA in US
• Risk factor Barrett esophagus
• Distal 1/3 of esophagus
• Symptoms insidious onset late obstruction

• Squamous cell carcinoma
• More common than adenocarcinoma worldwide
• Risk factors esophagitis, smoking, alcohol,
  genetics
• Middle 1/3 of esophagus
• Symptoms insidious onset late obstruction

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Adenocarcinoma of esophagus
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Adenocarcinoma of esophagus
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GI Pathology Outline

• Esophagus
• Stomach
• Gastritis
• Ulcers
• Gastric carcinoma

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Chronic Gastritis

• Chronic Inflammation in mucosa, leading
  eventually to mucosal atrophy and epithelial
  metaplasia
• Symptoms asymptomatic, or discomfort
• Cause Helicobacter pylori, autoimmune gastritis
• Helicobacter also causes ulcers, gastric
  carcinoma, and MALT lymhoma
• Danger intestinal metaplasia (precancerous)

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Chronic gastritis
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Chronic gastritis
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Helicobacter pylori organisms
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Helicobacter pylori
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TFSS
VacA protein
CagA protein
holes
free radicals
cytokines
immobilized T-helper cells
Type IV Secretion System
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What happens after infection?
Helicobacter infection
Asymptomatic gastritis
Ulcer
Symptomatic gastritis
Carcinoma
Lymphoma
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Acute Gastritis

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

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Ulcer

• Erosion of mucosa into submucosa
• Causes H. pylori, NSAIDs
• Symptoms epigastric pain, bleeding, perforation
• Also can occur after severe physiologic stress
  (trauma, buns, CNS trauma)

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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!

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Ulcer
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Stress ulcers
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Gastric Cancer

• Intestinal type
• Arises in intestinal metaplasia
• Risk factors chronic gastritis, diet (?nitrites,
  ? fruits/vegetables)
• Glandular morphology
• Generally asymptomatic

• Diffuse type
• Arises from gastric glands
• Risk factors undefined
• Signet ring morphology
• Generally asymptomatic

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Helicobacter infection
gastritis
atrophy
intestinal metaplasia
dysplasia
carcinoma
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Intestinal-type gastric carcinoma glands
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Diffuse gastric carcinoma signet ring cells
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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
• Diverticular disease
• Infectious diarrhea
• Inflammatory bowel disease
• Tumors

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Diverticulosis

• Herniation of mucosa/submucosa through muscle
  wall
• Older patients, low fiber diet, increased
  intraluminal pressure
• Sigmoid colon
• Asymptomatic unless infected (diverticulitis)

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Diverticulosis
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Diverticulosis
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Diverticulosis
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Infectious Diarrhea

• Major problem worldwide
• Viral
• Rotavirus (60 of childhood diarrhea in US)
• Calcivirus (older children, adults)
• Bacterial
• Several different organisms
• Differing mechanisms, sources
• Most cause mucosal damage and inflammation some
  cause massive water influx or mucosal ulceration

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Selected causes of bacterial diarrhea
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Hemorrhagic colitis
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Microangiopathic hemolytic anemia
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Pseudomembranous colitis
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Pseudomembranous colitis
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Inflammatory Bowel Disease

• Crohn Disease
• Ileum mostly (but can be anywhere)
• Patchy involvement
• Transmural inflammation, fistulas, strictures
• Granulomas
• Poor response to surgery
• Increased risk for cancer

• Ulcerative Colitis
• Colon only
• Continuous involvement
• Superficial inflammation
• No granulomas
• Good response to surgery
• Increased risk for cancer

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Crohn disease
Ulcerative colitis
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Adenoma

• Common! 50 of people gt60.
• Epithelial proliferation and dysplasia
• Tubular, villous, or tubulovillous
• More dangerous when
• Large (gt1 cm)
• Villous architecture
• Severe dysplasia

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Colon polyp
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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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Colorectal Carcinoma

• Almost always arises in adenomatous polyp
• Peak age 60-70
• Dietary risk factors low fiber, high fat, lots
  of unrefined carbs, not enough vitamins (A, C, E)
• Symptoms
• silent for years
• fatigue, weakness, iron-deficiency anemia
• occult bleeding, crampy pain
• Prognosis 5ys 90 if stage 1, 4 if stage 4

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Colon carcinoma
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Colon carcinoma
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GI Pathology Outline

• Esophagus
• Stomach
• Intestine
• Liver
• Hepatitis (viral, autoimmune, alcoholic)
• Hemochromatosis
• Wilson disease
• Neoplasms of the liver

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Normal liver
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Normal liver
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Patterns of Liver Injury

• Degeneration and intracellular accumulation
• Necrosis and apoptosis
• Regeneration
• Inflammation (hepatitis)
• Fibrosis
• Cirrhosis

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Clinical Syndromes

• Hepatic failure
• Cirrhosis
• Portal hypertension
• Jaundice

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Clinical Syndromes

• Hepatic failure
• Jaundice, edema, hyperammonemia
• Toxin accumulation damages organs
• Coagulopathy leads to bleeding
• Hepatic encephalopathy
• Hepatorenal syndrome

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Clinical Syndromes

• Hepatic failure
• Cirrhosis
• Fibrosis, nodules in liver
• Alcoholism, hepatitis
• Anorexia, weakness, liver failure, liver carcinoma

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Clinical Syndromes

• Hepatic failure
• Cirrhosis
• Portal hypertension
• Ascites
• Portosystemic venous shunts
• Congestive splenomegaly
• Hepatic encephalopathy

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Consequences of portal hypertension

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Clinical Syndromes

• Hepatic failure
• Cirrhosis
• Portal hypertension
• Jaundice
• Elevated bilirubin
• Conjugated (decreased liver excretion of
  bilirubin) or unconjugated (excess production of
  bilirubin)
• Congestive

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Bilirubin metabolism and elimination

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Clinical Consequences of Liver Disease

• Severe liver dysfunction
• Jaundice, cholestasis
• Hypoalbuminemia
• Hyperammonemia
• Hypoglycemia
• Hypogonadism
• Weight loss
• Muscle wasting

• Portal hypertension
• Ascites
• Splenomegaly
• Esophageal varices
• Hemorrhoids
• Caput medusae

• Complications of liver failure
• Coagulopathy
• Hepatic encephalopathy
• Hepatorenal syndrome

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Oral Manifestations of Liver Injury

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

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Laboratory Tests
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Infectious Hepatitis

• Viral hepatitis is the most common liver
  infection
• Asymptomatic
• Acute viral hepatitis (jaundice)
• Chronic viral hepatitis (fatigue may ?
  cirrhosis)
• Fulminant viral hepatitis (massive liver
  necrosis)

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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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Cirrhosis
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Cirrhosis
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Ridiculously Oversimplified Summary
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Hepatitis B outcomes
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Hepatitis C outcomes
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Autoimmune Hepatitis

• FgtgtM
• No viral hepatitis markers
• High titers of autoantibodies (antinuclear,
  anti-smooth muscle, anti-microsomal)
• Associated with other autoimmune diseases
  (rheumatoid arthritis, ulcerative colitis)
• Risk of cirrhosis 5
• Treatment immunosuppressive drugs

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Alcoholic Liver Disease

• Alcohol abuse causes 100,000 -200,000 deaths
  annually (20,000 due to end-stage liver
  cirrhosis)
• Effects on liver steatosis, hepatitis, cirrhosis
• Short-term ingestion of 8 beers/day (7 oz. 80
  proof liquor) leads to reversible steatosis
• Long-term ingestion of 5-6 beers/day leads to
  severe injury
• Beer and binge drinking are risky

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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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Alcoholic Liver Disease Prognosis

• Abstinence 5ys is 90 (if jaundice, ascites, or
  hematemesis have not developed)
• Continued drinking 5ys drops to 50-60
• Causes of death in end-stage alcoholism
• Liver failure
• Massive GI bleed
• Infection
• Hepatorenal syndrome
• Hepatocellular carcinoma

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Hereditary Hemochromatosis

• Autosomal recessive disease ? body iron
• Cause mutations in hemochromatosis gene
  (regulates iron absorption)
• MgtF, 50-60 years old
• Liver cirrhosis, skin pigmentation, diabetes,
  increased risk of hepatocellular carcinoma
• Early detection and treatment (phlebotomy, iron
  chelators) normal life expectancy

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Wilson Disease

• 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
• Diagnosis increased hepatic copper levels,
  decreased serum ceruloplasmin
• Treatment copper chelation therapy

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Kayser-Fleischer Rings
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Biliary Disease

• Secondary biliary cirrhosis
• due to bile obstruction by stones, atresia, tumor
• Primary biliary cirrhosis
• immune-mediated destruction of bile ducts
• women, 40s 50s
• anti-mitochondrial antibodies
• Primary sclerosing cholangitis
• chronic fibrosis of bile ducts
• men, 20s 40s
• associated with ulcerative colitis

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Primary biliary cirrhosis
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Primary sclerosing cholangitis
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Hepatic Adenoma

• Women of childbearing age on oral contraceptives
• Regresses with discontinuation of hormones
• May be mistaken for carcinoma
• May rupture during pregnancy, leading to
  life-threatening intra-abdominal hemorrhage

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Hepatic adenoma
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Hepatic adenoma
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Hepatocellular Carcinoma

• Strongly associated with hepatitis B and C,
  chronic liver disease, and aflatoxins
• Rapid increase in liver size, worsening ascites,
  fever and pain
• Very elevated alpha fetoprotein level
• Median survival 7 months (death from bleeding,
  liver failure, profound cachexia)

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Hepatocellular carcinoma
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Hepatocellular carcinoma
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Metastatic Carcinoma

• The most common malignant tumor in the liver
• Usually multiple lesions
• Most common primaries colon, lung, breast,
  pancreas, stomach.

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Metastatic carcinoma
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GI Pathology Outline

• Esophagus
• Stomach
• Intestine
• Liver
• Gallbladder
• Cholelithiasis
• Cholecystitis

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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

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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
• Pancreatic carcinoma

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Normal Pancreas

• Exocrine pancreas
• Makes enzymes for digestion
• Diseases Pancreatitis, cystic fibrosis, tumors
• Endocrine pancreas
• Makes insulin, glucagon, other stuff
• Diseases Diabetes, tumors

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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
• Complications DIC, ARDS, shock, endotoxemia,
  infection
• Prognosis Most recover 5 mortality in first
  week

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Obstruction (gallstones)
Cell injury (alcohol)
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Chronic Pancreatitis

• Longstanding, irreversible pancreatic destruction
• Most are alcohol related, some idiopathic
• Symptoms silent, or bouts of jaundice and pain
• Diagnosis difficult
• Complications secondary diabetes, malabsorption,
  severe chronic pain
• Prognosis poor (50 mortality over 20 years)

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Pancreatic Adenocarcinoma

• 4th leading cause of cancer death in US
• Risk factor smoking
• Highly invasive
• Silent until late then pain, jaundice
• Very high mortality 5ys lt5

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Pancreatic carcinoma
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Pancreatic carcinoma