Bilirubin is derived from the haemoglobin of aged or damaged red blood cells. Bilirubin does not contain iron, but is rather a derivative of the heme group. Some part of serum bilirubin is carried in the plasma to the liver, where it is conjugated to form bilirubin di-glucuronide and excreted in the bile. Conjugated bilirubin is also referred “direct bilirubin” because of the fact it reacts directly with the analytical reagent without any solubilising agent. The unconjugated bilirubin is referred to as indirect bilirubin. Total bilirubin includes both the conjugated and unconjugated (free) forms and, if elevated, is usually indicative of liver damage or haemolysis.

Serum bilirubin concentration reflects the ability of hepatocytes to take up, conjugate and secrete bilirubin, so it is a functional marker rather than a marker of cellular integrity as reflected by serum transaminase levels. In the absence of biliary obstruction, total bilirubin is an insensitive measure of liver function; due to the large reserve capacity of the liver for bilirubin processing, considerable hepatic injury must occur before alterations in total bilirubin are detectable. This means that by the time total bilirubin elevates, substantial hepatic injury has occurred. The combination of ALT and bilirubin is used in “Hy’s Law” which states that, in drug-induced liver injury, elevation of both ALT and bilirubin is more indicative of serious liver injury than is elevation in serum enzymes alone.

Serum bilirubin levels are used to rule out clinical conditions:

1. Pre-hepatic:   Haemolytic crisis
2. Hepatic:   Hepatic disease (decreased ability to conjugate and excrete bilirubin), Intrahepatic cholestatic disease
3. Post-hepatic: Bile duct obstruction results in an accumulation of conjugated bilirubin.