All you need to know about bilirubin (and liver function)

A liver function panel always includes tests for bilirubin levels. Let’s review how bilirubin is formed and eliminated from the body, and how it’s measured in a clinical laboratory.

Bilirubin is a waste product produced by the breakdown of red blood cells. Bilirubin is the end-product of heme metabolism; the liver is the site for bilirubin metabolism.

Hemoglobin is broken down into heme, which is converted to biliverdin, and finally into unconjugated bilirubin (which is not water-soluble). In the bloodstream, unconjugated bilirubin binds with serum proteins—most commonly albumin. The unconjugated bilirubin is then taken up by the liver.

In the liver, the unconjugated bilirubin is bound to glucuronide by the enzyme uridine 5’-diphospho-glucuronosyltransferase (UDP) and becomes conjugated bilirubin. Conjugated bilirubin is then excreted in bile.

In the intestines, bacterial enzymes hydrolyze conjugated bilirubin to release free, unconjugated bilirubin, which is reduced to urobilinogen. Urobilinogen, bound to albumin, is then excreted in urine.

In the intestines, some urobilinogen is converted to stercobilinogen and excreted in the stool. Thus, in normal urine, only urobilinogen is present; in normal stool, only stercobilinogen is present.

Cholestatic or obstructive jaundice occurs when liver cells are unable to transport bilirubin through the hepatic-bile capillary membrane because of damage in the liver. Obstructive jaundice can also occur when transport through the biliary tract is blocked because of anatomical obstructions such as gallstones or cancer.

In obstructive jaundice, conjugated bilirubin regurgitates into the blood. Because it is water-soluble, bilirubin is excreted into the urine. This is called choluria, or the presence of bile in the urine.

As well, less conjugated bilirubin is taken up by the intestines in obstructive jaundice. As a result, less stercobilinogen is found in the stool and the stool appears pale.

In the clinical laboratory, conjugated bilirubin is measured as direct bilirubin. If we take the total bilirubin and subtract the direct bilirubin, it provides the concentration of unconjugated bilirubin (also referred to as indirect bilirubin).

This concludes our review of bilirubin metabolism and how it’s measured in the laboratory. For your reference, here are the normal values of bilirubin in adults:

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