Bilirubin and Jaundice

Unconjugated hyperbilirubinaemia

• Pre-hepatic (acholuric)
• Hepatocellular

Conjugated hyperbilirubinaemia

• Hepatocellular
• Intrahepatic obstruction
• Extrahepatic obstruction

Note:

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

Unconjugated hyperbilirubinaemia

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
  • pernicious of prematurity
• Congenital
  • Gilbert 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 (hepatic canalicular disorders)
  • Hepatitis (viral)
  • Cirrhosis (Primary biliary cirrhosis)
  • Intrahepatic cholestasis
  • Drugs
    • indomethacin, erythromycin
    • chlorpromazine, isoniazid, flucloxacillin, OCP
  • Congenital
    • Dubin–Johnson syndrome
    • Rotor 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 hyperbilirubinaemia – 35 micromol/L
  • Unconjugated hyperbilirubinaemia – 45 micromol/L
• Ratio of unconjugated and conjugated helps to determine cause of hyperbilirubinaemia
  • 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 syndrome, Gilbert syndrome)
  • Conjugated – Complete extrahepatic obstruction
• Increased levels
  • Unconjugated – haemolysis, highly alkaline urine or eating bananas up to 48 hours before test