Liver Cirrhosis

Question 1

What are the two features of the liver damage from cirrhosis?

Answer 1

1) Disruption of normal hepatic parenchyma by bands of fibrosis
2) Regenerative nodules of hepatocytes

Question 2

What mediates the fibrosis in cirrhosis?

Answer 2

TGF-beta from stellate cells

Question 3

What are the clinical features of Cirrhosis?

Answer 3

1) Portal hypertension
- Ascites
- Congestive splenomegaly/ hypersplenism
- Portosystemic shunts (esophageal varices, hemorrhoids, caput medusae)
- Hepatorenal syndrome

2) Decreased detoxification
- Mental status change/Asterixis/Coma (increased ammonia)
- Gynecomastia, spider angiomata, palmar erythema (increased estrogen)
- Jaundice

3) Decreased protein synthesis
- Hypoalbuminemia with edema
- Coagulopathy

Question 4

What are the 3 effects of alcohol on the liver?

Answer 4

1) Fatty liver
2) Alcoholic hepatitis
3) Cirrhosis

Question 5

What is the mechanism, symptoms and path of alcoholic hepatitis?

Answer 5

Etiology: Acetaldehyde (metabolite of alcohol) mediates damage

Symptoms: Painful hepatomegaly, elevated liver enzymes (AST>ALT)

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

Question 6

What is hemochromatosis?

Answer 6

Excess body iron leading to deposition in tissues (hemosiderosis) and organ damage (hemochromatosis).

Question 7

What mediates the tissue damage in hemochromatosis?

Answer 7

Generation of free radicals from excess iron

Question 8

What are the causes of primary and secondary hemochromatosis?

Answer 8

• Primary hemochromatosis: Autosomal recessive defect in iron absorption due to HFE gene, usually C282Y
• Secondary hemochromatosis: Chronic transfusions

Question 9

What is the classic triad of hemochromatosis?

Answer 9

• Cirrhosis
• Secondary diabetes mellitus
• Bronze skin

Question 10

What stain is used to distinguish iron from lipofuscin in a liver biopsy?

Answer 10

Prussian blue stain
- Lipofuscin is a brown pigment that is a by-product from the turnover of peroxidized lipids; commonly present in hepatocytes

Question 11

What is the treatment for hemochromatosis?

Answer 11

Phlebotomy

Question 12

What is Wilson Disease?

Answer 12

Autosomal recessive defect (ATP7B gene) in ATP-mediated hepatocytes copper transport resulting in lack of copper transport into bile and lack of copper incorporation into ceruloplasmin

Question 13

What causes excess copper to damage tissue?

Answer 13

Copper-mediates production of hydroxyl free radicals

Question 14

What are the symptoms of Wilson’s Disease?

Answer 14

• Cirrhosis
• Neurologic manifestations (Parkinson’s symptoms, chorea, dementia, behavioral changes)
• Kayser-Fleisher rings in the cornea

Question 15

What is Primary Biliary Cirrhosis?

Answer 15

Autoimmune granulomatous destruction of intrahepatic bile ducts

Question 16

What are associations with PBC?

Answer 16

• Women in their 40s

- Other autoimmune conditions

Question 17

What is Primary Sclerosing Cholangitis?

Answer 17

Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts

Question 18

What are the pathologic features of PSC

Answer 18

1) Periductal fibrosis with an onion-skin appearance

2) Uninvolved regions are dilated resulting in a “beaded” appearance on contrast

Question 19

What conditions are associated with PSC?

Answer 19

Ulcerative collitis, p-ANCA, increased risk for cholangiocarcinoma

Question 20

What is REYE syndrome?

Answer 20

Fulminant liver failure & Encephalopathy in children with viral illness who take ASPIRIN!!!

Question 21

What are the presenting symptoms of REYE syndrome?

Answer 21

• Hypoglycemia
• Elevated liver enzymes
• Nausea/Vomiting
• Coma, Death

Question 22

What is a hepatic adenoma? Associations? Concern?

Answer 22

• Benign tumor of hepatocytes
• Associated with oral contraception use; regresses with cessation
• Risk of rupture and intraperitoneal bleeding because they are subcapsular; especially during pregnancy with exposure to excess estrogen

Question 23

What are the risk factors for hepatocellular carcinoma?

Answer 23

• HepB, Hep C
• Wilson’s Disease
• Hemochromatosis
• Alcohol
• Alpha-1-Antitrypson deficiency
• Non-fatty liver disease
• Aflatoxins derived from Aspergillus (induces p53 mutations)

Question 24

What complication do we worry about with hepatocellular carcinoma?

Answer 24

-Budd-Chiari syndrome: liver infarction econdary to hepatic vein obstruction. Presents with hepatomegaly and ascites

Question 25

What is the serum marker for HCC?

Answer 25

Alpha-fetoprotein

Question 26

What are the most common sources of liver mets?

Answer 26

Colon, pancreas, lung, breast carcinoma