Pathology

Question 0

What is a hepatic adenoma? Associated with? Risks?

Answer 0

Benign epithelial tumor of liver (usually solitary mass)

Strongly associated with oral contraceptive use and anabolic steroids.
(grows with exposure to estrogen)

Risk of rupture and intraperitoneal bleeding (subcapsular tumor), especially during pregnancy.

Question 1

Causes of hemochromatosis? Primary vs. secondary. Increased risk of?

Answer 1

1) Primary: due to mutations in HFE gene (C282Y)
HFE normally detects circulating iron levels
defective key regulatory step in iron regulation of the body – hepatocytes uptake iron in duodenum but only passes iron into blood if there is a need (defective in hemochromatosis)

2) Secondary: due to blood transfusions

Question 2

What is the most common malignant hepatic lesion?

Answer 2

METASTASIS (colon, pancreas, lung, breast = most common)

Question 3

What are the physical hallmarks of cirrhosis? What mediates fibrosis?

Answer 3

bands of fibrosis and regenerative nodules
(surface usually smooth, but becomes nodular!)

TGFbeta from stellate cells (lie beneath the endothelial cells that line the sinusoids of the hepatic plates)

Question 4

What is the most common type of gallstone? What are risk factors for formation?
What is the other type of gallstone? What are risk factors for formation?

Answer 4

Cholesterol stones (yellow, radiolucent) = most common
Risk factors:
- estrogen
- cirrhosis (decreases bile salt production)
- low bile salts, low phosphotidylcholine (decreased cholesterol solubility)
- Crohn disease (bile salts normally recycled/picked up in terminal ileum)

Bilirubin stones (black, radiopaque)
Risk factors:
- extravascular hemolysis (increased bilirubin in bile)
- biliary tract infection (E. coli, Ascaris lumbricoides, Clonorchis sinensis)

Question 5

What do brown pigment stones indicate? Black?

Answer 5

brown pigment stones = radiolucent, most likely in cases of biliary tract infection

black pigment stones = radiopaque, most likely intravascular hemolysis

Question 6

How does infection lead to brown pigment stones?

Answer 6

release of beta-glucuronidase by injured hepatocytes and bacteria

hydrolysis of bilirubin glucuronides increases the amt of unconjugated bilirubin in bile

Question 7

55yo male with dark tan, cardiac arrhythimia, mild hepatomegaly? What chronic disease may develop? Mechanism of damage?

Answer 7

hemochromatosis

Secondary diabetes mellitus “bronze diabetes”
due to damage to islets (pancreas will have bronze color)

Iron accumulation leads to generation of free radicals = damage

Question 8

What is the treatment for porcelain gallbladder? How does it develop?

Answer 8

Cholecystectomy (prophylactic) - due to high rates of gallbladder carcinoma

dystrophic calcification due to chronic cholecystitis

Question 9

What is the hallmark sign of chronic cholecystitis? Sign on PE?

Answer 9

Rokitansky-Aschoff sinus
herniation of gallbladder mucosa into the muscular wall

Murphy sign positive - inspiratory arrest on RUQ palpation due to pain

Question 10

Lymphocytic infiltration and granulomatous destruction of interlobular bile ducts on liver biopsy? Presentation? Associations?

Answer 10

Primary biliary cirrhosis

Presents with symptoms of biliary tract obstruction (increased CB, cholesterol, ALP; jaundice, pruritis, dark urine/light stools, hepatosplenomegaly)

Associated with:

• increased serum mitochondrial antibodies
• other autoimmune conditions

Question 11

Findings in primary sclerosing cholangitis? Associations?

Answer 11

• concentric “onion skin” bile duct fibrosis (both intra- and extra-hepatic bile ducts)
• alternating strictures (affected regions) and dilation (unaffected) leading to “beading” of the ducts

Associated with ulcerative colitis and positive P-ANCA

Question 12

Histological findings of viral hepatitis? Lab findings? Presentation?

Answer 12

Histology:
- diffuse ballooning degeneration (hepatocyte swelling)
- apoptosis of hepatocytes
- mononuclear cell infiltrates
- Councilman bodies (eosinophilic apoptotic hepatocytes)
Seen in both lobules of liver and portal tracts

Lab findings: elevated liver enzymes (ALT > AST)

Presentaiton: jaundice (mixed CB and UCB) with dark urine (CB), fever, malaise, nausea, anorexia

Question 13

20yo with intermittent self-resolving jaundice with high total and direct bilirubin levels? Mechanism? Findings?

Answer 13

Dubin-Johnson syndrome
due to defective bilirubin canalicular transport protein (defective hepatocellular excretion of bilirubin glucuronides)

high direct bilirubin = conjugated bilirubin

usually asymptomatic – liver will be dark/black!
histologically normal, but dense pigment of epinephrine metabolites within lysosomes may be seen

Question 14

Pt with ileal resection – why are pts on total parenteral nutrition at risk for gallstone formation?

Answer 14

• absent enteral stimulation secondary to decreased CCK release = biliary stasis
• in ileal resection, disturbance of enterohepatic bile acid circulation (loss of bile acids)

Question 15

Which hepatitis viruses increase hepatocellular carcinoma risk? Mechanism?

Answer 15

HBV, HCV (also HDV)

HBV integrates its DNA into the host genome to increase HCC risk:

• chronic injury and regenerative hyperplasia increases mt risk
• encoded HBx protein acts as an oncogene

Question 16

30yo pt with progressive exertional dyspnea and elevated liver enzymes? Mechanism? Associated findings on biopsy?

Answer 16

Alpha-1 antitrypsin (A1AT) deficiency
serum protein that reduces tissue damage caused by inflammation by inhibition of neutrophil elastase

Periodic acid-Schiff staining shows reddish-pink intracellular globules of accumulated misfolde, unsecreted A1AT in hepatocytes.

Question 17

Pt with Sjögren’s syndrome, pruritis, increased CB, ALP, AST > ALT? Most common in which demographic?

Answer 17

Primary biliary cirrhosis

autoimmune destruction of the intrahepatic bile ducts and cholestasis = elevated alkaline phosphatase

middle-aged women

Question 18

Liver mass with increased serum AFP level? Risk factors?

Answer 18

Hepatocellular carcinoma

Risk factors:

• chronic hepatitis (HBV - integration into genome; HCV - inflammation)
• cirrhosis (alochol, hemochromatosis, A1ATdef., Wilson disease)
• aflatoxins from Aspergillus (induces p53 mutation)

Question 19

What is Budd-Chiari syndrome? Presentation?

Answer 19

obstruction of hepatic vein
liver infarction that presents with painful hepatomegaly and ascites

biopsy would show centrilobular congestion and fibrosis

Question 20

Pt with esophageal varices, enlarged spleen, normal liver biopsy?

Answer 20

Portal vein thrombosis

normal liver biopsy shows portal HTN is PRE-SINUSOIDAL!
ascites seen in Budd-Chiari uncommon due to pre-sinusoidal obstruction

Question 21

Countries that store moldy grains are at risk for?

Answer 21

Aspergillus and HCC

Aflatoxins induce p53 mutations that increase risk for hepatocellular carcinoma!

Question 22

Copper ring found in eye of pt with chronic hepatitis? Inheritance? Findings and associations? Treatment?

Answer 22

Kayser-Fleischer ring
Wilson disease (autosomal recessive)

Presents in childhood with:

• cirrhosis
• neurologic manifestations – deposits in basal ganglia leading to Huntington-like and Parkinsonian symptoms)
• Kayser-Fleischer rings

Lab values:

• decreased ceruloplasmin
• increased urinary copper and liver copper on biopsy

Increased risk of hepatocellular carcinoma

Treatment: copper chelators (D-penicillamine or trientine)

Question 23

What are the stages of alcoholic liver disease? Hallmarks of each? Most important prognostic determinants?

Answer 23

Alcoholic steatosis (reversible)
Alcoholic hepatitis (reversible)
Alcoholic cirrhosis (irreversible)

Question 24

Histological findings in Reye syndrome? Other findings?

Answer 24

microvesicular steatosis of hepatocytes (without inflammation) – fatty liver

hypoglycemia, vomiting, hepatomegaly, coma

Question 25

Hydatid cysts in liver caused by? Risk if ruptured during removal? Treatment?

Answer 25

Echinococcus granulosus

Anaphylactic shock can result from spilling of cyst contents within the peritoneum.

Treatment: albendazole

Question 26

What is the mechanism of alcohol-induced hepatic steatosis?

Answer 26

decrease in free fatty acid oxidation
secondary to excess NADH production by alcohol dehydrogenase and aldehyde dehydrogenase (the two major alcohol metabolism enzymes)