Jaundice

Question 1

Normal handling of bilirubin

Answer 1

• Breakdown of RBCs - Heme
• becomes biliverdin via heme oxygenase
• becomes unconjugated bilirubin via biliverdin reductase
• transported to liver
• conjugation w glucuronic acid via UDP-glucuronyl transferase
• excretion of conjugated bilirubin into bile canliculi by MDR2 efflux pumps
• post hepatic modification of bilirubin (deconjugated by β-glucuronidase or degraded to uro/stercobilin)

Question 2

Causes of hyperbilirubinemia (3)

Answer 2

1. Pre-hepatic/Hemolytic - overproduction of bilirubin
   - eg hemolytic anemia
2. Hepatic/Hepatocellular - impaired liver cell uptake, conjugation, excretion of bilirubin
   - widespread hepatocellular disease - hepatitis, cirrhosis
   - Gilbert syndrome, Crigler-Najjar syndrome
   - physiologic jaundice of newborn (enzyme immaturity)
   - Dubin-Johnson syndrome, Rotor syndrome
3. Post-hepatic/Obstructive - obstruction to outflow of bile, cholestatic
   - gallstones
   - carcinomas of head of pancreas, bile duct, ampulla of Vater
   - extrahepatic biliary atresia

Question 3

Classification of hyperbilirubinemia

Answer 3

1. Predominantly unconjugated (pre-hepatic, hepatic)
   - uptake & conjugation affected
   - unconjugated - insoluble in water - complexed to albumin in blood - cannot be excreted in urine, can cross BBB (kernicterus in young children)
2. Predominantly conjugated (hepatic, post-hepatic)
   - excretion affected
   - conjugated - water soluble, only loosely bound to albumin in blood - excreted in urine, cannot cross BBB

Question 4

Clinical features of pre-hepatic jaundice

Answer 4

• jaundice - unconjugated - lemon yellow
• dark stools (stercobilin), normal urine (not filtered into urine)
• no pruritus (no bile accumulation)
• anemia w reticulocytosis, splenomegaly
• LFT- normal ALT, AST, alkaline phosphatase, GGT, liver proteins

Question 5

Clinical features of hepatic jaundice

Answer 5

• jaundice - conjugated - orange tint
• normal stools, tea coloured urine
• anorexia, hepatic tenderness, spleen normal/enlarged
• LFT - raised ALT & AST (AST>ALT - toxins, ALT>AST - viral), raised alkaline phosphatase & GGT, reduced liver proteins (chronic renal failure)

Question 6

Clinical features of post-hepatic jaundice

Answer 6

• jaundice - conjugated - greenish tinge
• pale stools (no bile pigment), dark urine (bilirubinuria, no urobilin)
• pruritus & scratch marks (bile accumulation)
• enlarged gall bladder
• LFT - ALT & AST mildly elevated, alkaline phosphatase & GGT raised, liver proteins normal