156. Biliary Tract Disorders

Question 1

Choledocholithiasis

• labs
• sx
• imaging
• tx

Answer 1

conjugated hyperbilirubinemia, high Alk-P

sx: RUQ pain, jaundice
imaging: ULTRASOUND (mrcp, ercp)
tx: fix obstruction w/ endoscopic/radiologic/surgical intervention

Question 2

Primary Biliary Cholangitis

• what is it
• epidemiology
• labs
• histo

Answer 2

slowly progressing liver disease of unknown etiology
F>M
Labs: high alk-p, high GGT, +AMA!!
Histo: bile duct inflammation (around bile duct/portal triad)

Question 3

Newborn Jaundice

• what is normal - why does this happen?
• causes

Answer 3

Normal: bilirubin peaks 4-5 days after birth, because UDP-GT is BIRTH-RELATED - activity turns on and increases following BIRTH

Causes: increased RBC breakdown (hemolysis, hematoma), enterohepatic circulation of bilirubin, medications, breast-milk jaundice, hepatobiliary disease

Question 4

Gilbert’s Syndrome

• what is it
• pathophys
• labs
• when does jaundice develop?

Answer 4

Mildly elevated unconj bili with no clinical consequences
Bili increases during fasting, exertion, infections
PPhys: 7TA’s instead of 6 in TATA box promotor for UDP-GT enzyme = decreased expression (but body well-compensates until stressed)
Labs: normal ALT, AST, Alk-P, Direct Bilirubin (high total bilirubin)

Jaundice develops only if L&R hepatic ducts (or CBD) obstructed - large capacity for regeneration unless pre-existing cirrhosis due to redundancy of metabolic pathways

Question 5

Alcoholic Liver Disease

• labs
• sx
• histo

Answer 5

High AST/ALT, AST:ALT > 2
sx: fatigue, pruritis, jaundice
Histo: steatosis, mallory bodies (inflammation)

Question 6

Sepsis

- pathophys of liver dysfx

Answer 6

Decreased expression of bile salt transporters following infection
downregulation of ATP-dependent canalicular hepatocyte transporters
due to acute phase response: use ATP to make other proteins instead of powering bili and bile acid transporters

Question 7

Intrahepatic Cholestasis of Pregnancy

• cause
• relation to another disease
• what is epistasis?

Answer 7

Polymorphisms of ABCB4/ABC canalicular liver transporters
Heterozygous mutation = subclinical until stressed (pregnancy, birth control)
High serum bile acids = PRURITIS
tx: ursodeoxycholic acid = decreases pruritis, normalizes LFTs, decrease serum bile acid, improve fetal outcomes

PFIC3: same mucation in ABCB4 (MDR3) transporter - but polygenic interactions cause more severe disease
tx: liver transplant

Epistasis: effect of one gene being dependent on presence of 1+ “modifier genes”
Gene-gene interactions: b/w or w/in genes leading to non-additive effects
Mutations have diff effects in combination than individually

Question 8

What do you need to rule out with conjugated hyperbilirubinemia?

Answer 8

OBSTRUCTION!