Bilirubin

Bilirubin and Jaundice

Unconjugated hyperbilirubinemia

• Pre-hepatic (acholuric)
• Hepatocellular

Conjugated hyperbilirubinemia

• Hepatocellular
• Intrahepatic obstruction
• Extrahepatic obstruction

Note:

• <20% of bilirubin conjugated = Unconjugated hyperbilirubinemia
• >50% of bilirubin conjugated = Conjugated hyperbilirubinemia

Unconjugated hyperbilirubinemia

Classification:

• Pre-hepatic (acholuric) (vast majority. Secondary to increased bilirubin production
• Hepatocellular. Secondary to reduced hepatocyte uptake of bilirubin.

Cause:

• Haemolysis (must be 2 x normal to be significant) – Rarely causes rise over 70 micromol/L
  • Haemolytic anaemia
  • Erythroblastosis foetalis
  • Kernicterus of prematurity
• Congenital
  • Gilbert’s disease (GD)
  • Crigler-Najjar syndrome (CS)
• Iatrogenic
  • Drugs: Chloramphenicol, gentamicin, pregnanediol
• Physiological
  • Neonatal jaundice and Breast-milk jaundice

Conjugated hyperbilirubinaemia

• Hepatocellular – Diminished hepatocyte function. If severe can be associated with unconjugated hyperbilirubinemia due to total inability to conjugate bilirubin
  • Hepatitis – Viral, toxic, alcoholic, autoimmune
  • Cirrhosis
  • Leptospirosis
  • Drugs
    • Liver parenchymal injury (toxic hepatitis)
    • Halothane, paracetamol, methyldopa, phenytoin, barbiturates, MAOI, Sulphonamides
• Intrahepatic obstruction (Hepatocannalicular disorders)
  • Hepatitis (viral)
  • Cirrhosis (Primary biliary cirrhosis)
  • Intrahepatic cholestasis
  • Drugs
    • Indomethacin, erythromycin
    • Chlorpromazine, isoniazid, flucloxacillin, OCP
  • Congenital
    • Dubin-Johnson
    • Rotor’s syndrome
• Extrahepatic obstruction
  • Calculi, tumour, scar tissue in common bile duct or hepatic excretory duct
  • Gallstones, carcinoma of head of pancreas and lymphoma with extrinsic nodal compression of the porta hepatis are commonest

Serum Bilirubin

• Measures unconjugated and conjugated (Normal range: 6-24 micromol/L)
• Initial result details TOTAL bilirubin measured
• Clinically detectable jaundice
  • Conjugated hyperbilirubinemia – 35 micromol/L
  • Unconjugated hyperbilirubinemia – 45 micromol/L
• Ratio of unconjugated and conjugated helps to determine cause of hyperbilirubinemia
  • Predominantly unconjugated (<20% bilirubin conjugated)
  • Predominantly conjugated (>50% bilirubin conjugated)

Urine Bilirubin

• Ward Test Urine (WTU) or laboratory for may assess urine for Urine bilirubin and Urine urobilinogen
• Urine bilirubin
  • Conjugated bilirubin excreted into GIT is reabsorbed in very small amounts
  • Kidneys filter soluble form and it appears in urine
  • Bilirubin is NOT normally present in urine
  • Urine -dark in colour, usually brown with yellow foam
  • Presence of bilirubin implies Conjugated hyperbilirubinemia
• Urine urobilinogen -
  • Normal: 1-4mg/day (compared to 250mg in stool)
  • Absence of urobilinogen
    • Conjugated – Complete extrahepatic obstruction or Broad spectrum antibiotics destroying intestinal flora
  • Low levels of urobilinogen
    • Unconjugated – Congenital (Crigler-Najjar, Gilbert)
    • Conjugated – Complete extrahepatic obstruction
  • Increased levels
    • Unconjugated – Haemolysis, Highly alkaline urine or Eating bananas up to 48 hours before test