PA24.{1,6} | Bilirubin Metabolism, Jaundice & LFT Interpretation — Summary & Reflection

REFLECT

Before reviewing the summary, write brief answers to these questions in your notebook:

1. A patient has total bilirubin 8.4 mg/dL with indirect fraction 7.1 mg/dL, normal transaminases, urine urobilinogen 4+ but no urine bilirubin. What is the most likely mechanism and two differential diagnoses?

1. You receive a hepatitis B serology report: HBsAg negative, anti-HBs negative, anti-HBc IgM positive, anti-HBc IgG positive. What does this mean clinically, and what should you do next?

1. In Dubin-Johnson syndrome, why is urine bilirubin positive despite normal hepatocyte architecture?

Comparison: Check your answers against the blocks you have just studied. If any answer was incomplete, re-read the relevant block before proceeding to the MCQs.

KEY TAKEAWAYS

Bilirubin metabolism proceeds in three phases: (1) RES production of unconjugated bilirubin (UCB) from haem, bound to albumin; (2) hepatic uptake (OATP1B1/1B3), conjugation (UGT1A1), and canalicular export (MRP2) as conjugated bilirubin (CB); (3) intestinal conversion to urobilinogen/stercobilin with enterohepatic recirculation.

Jaundice classification by mechanism:
- Prehepatic: ↑ UCB, urine bilirubin −, urobilinogen ↑↑, dark stools, normal LFT enzymes.
- Hepatic: mixed bilirubin, urine bilirubin +, transaminases markedly ↑, synthetic markers impaired.
- Posthepatic: ↑ CB, urine bilirubin +++, urobilinogen absent, pale stools, ALP/GGT markedly ↑, pruritus.

Hereditary syndromes: Gilbert + Crigler-Najjar → unconjugated ↑ (UGT1A1 defect); Dubin-Johnson + Rotor → conjugated ↑ (MRP2 / OATP transport defects).

Neonatal jaundice: physiological (UCB from high RBC turnover + immature UGT1A1); treat with phototherapy; kernicterus risk in preterm and haemolytic disease.

LFT patterns: Hepatocellular (↑↑ ALT/AST) vs cholestatic (↑↑ ALP/GGT) vs prehepatic (↑ indirect bilirubin, normal enzymes). Synthetic reserve: albumin (chronic) and PT/INR (acute + chronic).

Hepatitis B serology key rules: (a) HBsAg + = active infection; (b) anti-HBs alone + = vaccination (no anti-HBc); (c) anti-HBs + anti-HBc IgG + = resolved natural infection; (d) anti-HBc IgM alone + = window period; (e) HBsAg + >6 months = chronic. HCV: anti-HCV detects exposure; HCV RNA confirms active replication.