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Bilirubin: Levels, Causes and Clinical Meaning

Bilirubin is a yellow-orange pigment produced during the breakdown of red blood cells. Elevated levels may indicate liver or bile duct disorders.

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Things worth knowing about "Bilirubin"

Bilirubin is a yellow-orange pigment produced during the breakdown of red blood cells. Elevated levels may indicate liver or bile duct disorders.

What is Bilirubin?

Bilirubin is a yellow-orange bile pigment produced as a byproduct of the natural breakdown of hemoglobin – the red pigment found in red blood cells (erythrocytes). As old or damaged red blood cells are broken down in the spleen, liver, and bone marrow, hemoglobin is dismantled into its components, one of which is bilirubin. It is then excreted through bile and is responsible for the characteristic brown color of stool.

Forms of Bilirubin

Bilirubin exists in two main forms in the body:

Indirect (unconjugated) bilirubin: This form is produced initially during hemoglobin breakdown and is water-insoluble. It is transported in the bloodstream bound to the protein albumin and is carried to the liver.
Direct (conjugated) bilirubin: In the liver, indirect bilirubin is chemically converted (conjugated) to become water-soluble. In this form, it can be excreted through bile into the intestine.

Normal Values and Measurement

Bilirubin levels are measured in the blood, typically as part of a liver function panel. Reference ranges may vary slightly between laboratories, but typical values are:

Total bilirubin: 0.2 – 1.2 mg/dL
Direct bilirubin: up to 0.25 mg/dL
Indirect bilirubin: up to 0.95 mg/dL

When bilirubin levels in the blood exceed a certain threshold, the pigment deposits in body tissues and causes the visible yellowing of the skin and eyes – a condition known as jaundice (icterus).

Causes of Elevated Bilirubin Levels

Elevated bilirubin (hyperbilirubinemia) can result from various causes, commonly grouped into three categories:

Pre-hepatic Causes (before the liver)

Excessive breakdown of red blood cells (hemolytic anemia)
Blood transfusion reactions
Hereditary conditions such as sickle cell disease or thalassemia

Hepatic Causes (within the liver)

Liver inflammation (hepatitis A, B, or C)
Liver cirrhosis
Fatty liver disease (alcoholic or non-alcoholic)
Gilbert syndrome – a common, harmless genetic condition with mildly elevated bilirubin

Post-hepatic Causes (after the liver)

Gallstones blocking the bile duct
Inflammation of the gallbladder (cholecystitis)
Tumors affecting the bile ducts or pancreas

Low Bilirubin Levels

Abnormally low bilirubin levels are generally not considered clinically significant. However, some research suggests that very low bilirubin levels may be associated with an increased risk of cardiovascular disease or inflammatory conditions, as bilirubin in small amounts may have antioxidant properties.

Bilirubin in Newborns

Newborns frequently have elevated bilirubin levels in the first days of life, a condition known as neonatal jaundice. This is most often harmless and self-limiting, occurring because the immature liver of a newborn cannot process bilirubin quickly enough. In cases of very high levels, phototherapy (treatment with blue light) may be used to break down bilirubin in the skin and prevent potential neurological damage.

Diagnosis and Treatment

Bilirubin is measured through a simple blood test. If levels are elevated, additional liver enzymes (such as ALT, AST, GGT, alkaline phosphatase) and imaging studies such as ultrasound of the liver and bile ducts are usually performed to identify the underlying cause.

Treatment always depends on the underlying condition:

Hepatitis is managed by treating the inflammation (e.g., antiviral medications or lifestyle adjustments).
Gallstones may require surgical removal.
Hemolytic disorders are treated with therapies aimed at reducing excessive red blood cell destruction.

References

Feldman, M., Friedman, L. S., Brandt, L. J. – Sleisenger and Fordtran's Gastrointestinal and Liver Disease. Elsevier, current edition.
Fargo, M. V., Grogan, S. P., Saguil, A. – Evaluation of Jaundice in Adults. American Family Physician, 2017; 95(3):164-168.
World Health Organization (WHO) – Newborn Health: Jaundice. Available at: https://www.who.int (accessed 2024).

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