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
Dipstick Urinalysis Normal Biliary obstruction Hepatic disease Haemolytic disease
Bilirubin Negative Positive Positive Negative
Urobilinogen Positive Negative/ Decreased Negative/ Decreased Increased
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