Definition

Jaundice (icterus) refers to the yellow pigmentation of skin, sclerae and mucosae due to raised plasma bilirubin (>35 mmol/l).

Pathophysiology

Bilirubin is a normal breakdown product of haemoglobin produced in the reticuloendothelial system following destruction of old red blood cells. The resulting unconjugated bilirubin is insoluble and carried to the liver bound to albumin. In the liver, the enzyme uridine diphosphateglucuronyl transferase conjugates this with glucuronic acid into water soluble conjugated bilirubin. This is then secreted into bile canaliculi, and ultimately enters the duodenum. Bilirubin is converted into urobilinogen in the terminal ileum and colon, of which up to 20% is reabsorbed into the portal circulation. This is then either re-excreted back into the bile or excreted by the kidneys into the urine. Increased production, failure of uptake, or conjugation all result in unconjugated bilirubinaemia and jaundice.

Classification

Pre-hepatic: excess unconjugated bilirubin production (from red blood cells) exhausts the liver's capacity to conjugate e.g. haemolytic anaemias (hereditary spherocytosis, sickle-cell disease, hypersplenism).

Hepatic: unconjugated hyperbilirubinaemia due to inborn failure of conjugation (Crigler Najjar syndrome) and inborn failure of bilirubin uptake (Gilbert's syndrome). Hepatocellular causes include cirrhosis, viruses (hepatitis A, B, C, E; Epstein-Barr), autoimmune diseases, drugs (paracetamol, halothane).

Post-hepatic: obstructive conjugated hyperbilirubinaemia may be due to intrahepatic obstruction (primary biliary cirrhosis, some hepatocellular disease) or extrahepatic obstruction (gallstones, carcinoma of the head of pancreas, cholangiocarcinoma, portal lymphadenopathy, and sclerosing cholangitis).

Symptoms

Pain, typically RUQ biliary colic, occurs when there is choledocholithiasis. Dull persistent pain may be present with acute hepatitis or bulky tumours in the liver.