Jaundice - Differential

• Becomes clinically evident at 2 mg/dL, and is best seen in sclerae and under tongue

• Bilirubin metabolism:
  • Unconjugated form is not soluble in water
  • Binding to albumin allows for transport to liver, where  glucuronidation occurs
  • Conjugated bilirubin is excreted into the biliary tree and GI tract, where it is metabolized by gut flora into urobilinogen/stercobilinogen/stercobilin, which gives stool its brown color
• Unconjugated hyperbilirubinemia:
  • Given that it is not soluble in water, does not appear in urine (per Dr. Verghese, G6PD deficiency and spherocytosis were once termed “congential acholuric jaundice,” and were in part diagnosed based on lack of bilirubin in urine)
  • Causes:
    • Hemolysis
    • Impaired hepatic uptake (Gilbert’s, drugs)
    • Impaired conjugation (Crigler-Najjar)
• Conjugated hyperbilirubinemia:
  • Characterized by bilirubinuria and pale stools (bilirubin unavailable for gut flora to metabolize)
  • Causes:
    • Impaired excretion: Dubin-Johnson, Rotor
    • Hepatocellular injury/intrahepatic obstruction: viral, EtOH, drugs, PBC, PSC, TPN, autoimmune, Wilson’s, A1AT, HHC, infiltrative disease
    • Extrahepatic obstruction: choledocholithiasis, malignancy, PSC, HIV cholangiopathy

(Christopher Woo MD, 1/28/11)