Investigation and management of jaundice

Haem molecules are degraded in macrophages to biliverdin and then to bilirubin, which is selectively removed by hepatocytes from sinusoidal blood and conjugated, chiefly with two glucuronic acid moieties. Conjugated bilirubin is excreted into the bile, but in many liver diseases it refluxes back into blood from which some is filtered into and darkens the urine (choluria). In the distal intestine, conjugated bilirubin is deconjugated and reduced to a series of uro- and stercobilinogens that give the normal colour to faeces. Jaundice is the clinical sign of hyperbilirubinaemia and usually indicates disease of the liver or biliary tree. Dark urine and pale stools indicate cholestasis. Stigmata of chronic liver disease do not define the cause of jaundice. Unconjugated hyperbilirubinaemia—presents with raised serum bilirubin levels and normal other liver-related blood tests. Causes include haemolysis and benign inherited unconjugated hyperbilirubinaemia (i.e. Gilbert’s syndrome). Conjugated hyperbilirubinaemia—routine liver-related blood tests cannot alone differentiate between intra- and extrahepatic causes of jaundice although high levels of transferases suggests hepatitis (e.g. viral, autoimmune) or hepatic necrosis (e.g. paracetamol). Alcohol and drug histories are needed in those with both elevated alkaline phosphatase and transferases. Extrahepatic cholestasis should be sought by abdominal ultrasonography to detect a dilated intra- and/or extrahepatic biliary tree (and often also to reveal its cause, e.g. gallstones, tumour). Further investigation depends on the clinical context: (1) likely large bile duct disease—endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiography, and endoscopic ultrasonography; (2) likely intrahepatic cholestasis—autoantibodies, immunoglobulins, and liver biopsy.