Jaundice

Background

• Jaundice is yellow discolouration of the body due to excess bilirubin (i.e. hyperbilirubinemia)
• Divided into conjugated (direct) and unconjugated (indirect)

Pathophysiology

• Unconjugated bilirubin is a degradation product of heme, produced by defective or end-of-life erythrocytes
  • Heme is metabolized to biliverdin and then to unconjugated bilirubin in the reticuloendothelial system
• The unconjugated bilirubin is bound to albumin and transported to the liver, where the hepatocytes take it up and conjugate it to glucuronic acid
• Conjugated bilirubin is soluble in bile and excreted into the bile canaliculi, where it proceeds down the bile ducts and is stored in the bile ducts
• Conjugated bilirubin eventually reaches the small bowel through the common bile duct and ampulla of Vater
• Colonic bacteria deconjugate bilirubin and metabolize it into urobilinogen
  • 80% is metabolized into stercolin and excreted in stool
  • 20% is reabsorbed and enters back into enterohepatic circulation
  • Some urobilinogen that is reabsorbed is then excreted in urine, where it oxidizes to urobilin and causes yellowing of urine

Etiologies

• Divided into conjugated hyperbilirubinemia (>50% conjugated) and unconjugated hyperbilirubinemia (<20% conjugated)

Unconjugated Hyperbilirubinemia

• Overproduction: hemolysis, Wilson disease, extravasation, shunt hyperbilirubinemia
• Reduced uptake: portosystemic shunt, drugs, Gilbert syndrome
• Conjugation defect
  • Acquired: neonatal, maternal milk, Lucy-Driscoll, hyperthyroidism, chronic persistent hepatitis, advanced cirrhosis
  • Inherited: Crigler-Najjar syndrome, Gilbert syndrome

Conjugated or Combined Hyperbilirubinemia

• Intrahepatic cholestasis: PBC, PSC, viral hepatitis, progressive familial intrahepatis cholestasis, intrahepatic cholestasis of pregnancy, total parenteral nutrition, post-operative
  • Drugs and toxins: alcoholic hepatitis, corticosteroids, chlorpromazine, some herbal medications, arsenic
  • Infiltrative diseases, including amyloidosis, lymphoma, sarcoidosis, tuberculosis
  • Sickle cell crisis
• Extrahepatic cholestasis: HIV cholangiopathy, choledocholithiasis, tumours, PSC, pancreatitis, strictures
  • Some parasites: Ascaris lumbricoides, liver flukes
• Hepatocellular injury
• Defects in canalicular extretion or sinusoidal re-uptake: Dubin-Johnson syndrome, Rotor syndrome

Clinical Manifestations

• Can be seen in the sclera (scleral icterus) earliest, then skin
• Skin can take on a greenish hue over time, due to accumulation of biliverdin

Differential Diagnosis

• Carotenoderma, yellowing of the skin which spares the sclerae and is caused by excessive intake of carotene-rich foods