Total bilirubin comprises unconjugated, conjugated and delta bilirubin, whereas direct bilirubin comprises conjugated and delta bilirubin.
High levels of total and direct bilirubin are seen with hepatocellular disease or biliary disease (intra- or extra-hepatic).
Delta bilirubin, which is covalently bound to albumin, has a longer half-life in the circulation than the other bilirubins and may cause bilirubin elevation for some time after the others have returned to normal.
Isolated elevation of unconjugated bilirubin (that is, elevated total bilirubin with normal direct bilirubin) occurs when the rate of production exceeds the rate of conjugation. It is seen in Haemolysis and in Megaloblastic anaemia, but the commonest cause is Gilbert's syndrome, in which there is a non-pathological impairment of bilirubin conjugation.
Physiological jaundice in neonates is due to elevated unconjugated bilirubin.
Normal levels of bilirubin may be present in uncomplicated Cirrhosis, early in the course of fulminant liver failure, or with hepatic metastases until the disease is advanced.
Yellow skin colour with normal bilirubin may be due to carotenaemia.