Exocrine Pancreas, Galbladder And Liver Pathology Part Ii

Front 1

Cirrhosis

Back 1

End-stage liver damage characterized by disruption of normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes

Front 2

What mediates fibrosis in cirrhosis?

Back 2

fibrosis is mediated by TGF-β from stellate cells which lie beneath the endothelial cells that line the sinusoids

Front 3

What does portal hypertension in cirrhosis lead to?

Back 3

• Ascities
• Congestive splenomegaly/hypersplenism
• Portosystemic shunts (esophageal varices, hemorrhoids, and caput medusae)
• Hepatorenal syndrome (rapidly developing renal failure secondary to cirrhosis)

Front 4

What does decreased detoxification in cirrhosis lead to?

Back 4

• Mental status changes, asterixis, and eventual coma (due to increased serum ammonia); metabolic, hence reversible
• Gynecomastia, spider angiomata, and palmar erythema due to hyperestrinism
• Jaundice

Front 5

Decreased protein synthesis due to cirrhosis leads to?

Back 5

• Hypoalbuminemia with edema
• Coagulopathy due to decreased synthesis of clotting factors (degree of deficiency is followed by PT)

Front 6

Most common cause of liver disease in the West

Back 6

Alcohol

Front 7

How does alcoholic hepatitis present? (clinical + labs)

Back 7

Presents with painful hepatomegaly and elevated liver enzymes (AST > ALT); may result in death

Front 8

What mediates the damage in alcoholic hepatitis?

Back 8

Acetaldehyde

Front 9

What are the histological findings in alcoholic hepatitis?

Back 9

swelling of hepatocytes with formation of Mallory bodies (damaged cytokeratin filaments), necrosis, and acute inflammation

Front 10

Nonalcoholic fatty liver disease

Back 10

• Fatty change, hepatitis, and/or cirrhosis that develop without exposure to alcohol
• Associated with obesity
• Diagnosis of exclusion; ALT > AST

Front 11

Primary hemochromatosis

Back 11

Due to mutations in HFE gene, usually C282Y (cysteine is replaced by tyrosine at amino acid 282)

Front 12

How does hemochromatosis present?

Back 12

• Late adulthood
• Class triad is cirrhosis, secondary diabetes mellitus, and bronze skin
• Other findings include dilated cardiomyopathy, cardiac arrhythmias and gonadal dysfunction (due to testicular atrophy)

Front 13

Lab findings in hemochromatosis

Back 13

↓ TIBC, ↑ ferritin, ↑ serum iron, ↑ % saturation

Front 14

Findings on liver biopsy in hemochromatosis

Back 14

• Reveals accumulation of brown pigment in hepatocytes
• Prussian blue stain distinguishes iron (blue) from lipofuscin (brown pigment that is by-product from turnover of peroxidized lipids - commonly present in hepatocytes)

Front 15

What is the gene defect in Wilson disease?

Back 15

Autosomal recessive defect (ATP7B gene) in ATP-mediated hepatocyte copper transport

Front 16

Pathophysiology Wilson disease

Back 16

• Defective transport gene results in lack of copper transport into bile and lack of copper incorporation into ceruloplasmin
• Copper builds up in hepatocytes, leaks into serum, and deposits in tissues leading to free radical damage
• Increased risk of hepatocellular carcinoma

Front 17

How does Wilson disease present?

Back 17

• Presents in childhood
• Cirrhosis
• Neurologic manifestations (behavioral changes, dementia, chorea, and Parkinsonian symptoms due to deposition of copper in basal ganglia)
• Kayser-Fleisher rings in the cornea

Front 18

Lab findings in Wilson disease

Back 18

• ↑ urinary copper
• ↑ copper on liver biopsy
• ↓ serum ceruloplasmin

Front 19

Treatment of Wilson disease

Back 19

D-penicillamine (chelates copper)

Front 20

Primary biliary cirrhosis

Back 20

• Autoimmune granulomatous destruction of intrahepatic bile ducts
• Classically arises in women (avg. age 40 yrs)
• Associated with other autoimmune diseases
• Presents with features of obstructive jaundice
• Cirrhosis is late complication

Front 21

Which antibody is present in primary biliary cirrhosis?

Back 21

Antimitochondrial antibody present

Front 22

Primary sclerosing cholangitis

Back 22

• Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts
• Associated with ulcerative colitis (p-ANCA often positive)
• Presents with obstructive jaundice; cirrhosis is a late complication
• Increased risk for cholangiocarcinoma (cancer of bile ducts)

Front 23

How does primary sclerosing cholangitis appear on imaging?

Back 23

• Periductal fibrosis with an 'onion-skin' appearance
• Uninvolved regions are dilated resulting in a "beaded" appearance on contrast imaging

Front 24

Reye Syndrome

Back 24

• Fulminant liver failure and encephalopathy in children with viral illness who take aspirin
• Likely related to mitochondria damage of hepatocytes
• Presents with hypoglycemia, elevated liver enzymes, and nausea with vomiting; may progress to coma and death

Front 25

Hepatic adenoma

Back 25

• Benign tumor of hepatocytes
• Assoc. w/ oral contraceptive use; regresses upon cessation of drug
• Risk of rupture and intraperitoneal bleeding, esp. during pregnancy (high E2 drives growth of tumor)
• Tumors are sub capsular and grow with exposure to estrogen

Front 26

Risk factors for hepatocellular carcinoma

Back 26

• Chronic hepatitis (eg HBV and HCV)
• Cirrhosis (e.g., alcohol, nonalcoholic fatty liver disease, hemocrhomatosis, Wilson disease, and A1AT deficiency)
• Aflatoxins derived from Aspergillus (induce p53 mutations)

Front 27

Serum tumor marker for hepatocellular carcinoma

Back 27

Alpha-fetoprotein

Front 28

How can liver metastases be clinically detected?

Back 28

Hepatomegaly with a nodular free edge of the liver

Front 29

Budd-Chiari syndrome

Back 29

Liver infarction secondary to hepatic vein obstruction (e.g., carcinoma that invades vein); presents with painful hepatomegaly and ascites