Bilirubin is a normal, yellow-to-green pigment of bile. Although this biological pigment was long considered a waste product, it has antioxidant properties. About 80-85% result from breakdown of hemoglobin, while the remaining 15-20% result from breakdown of heme-containing proteins such as myoglobin, cytochromes, and catalases, and from maturation defects of erythrocytes in the bone marrow. Usually a small amount of bilirubin is found in the serum. Bilirubin is extremely insoluble in water and circulates in the blood bound to albumin protein. Albumin-bound bilirubin is taken up from the blood by liver cells (hepatocytes) where it is chemically converted by a process called conjugation into an increased water-soluble form. In conjugation, bilirubin undergoes a chemical reaction with a water-soluble compound glucuronic acid which results in the formation of a compound with two glucuronic acid molecules attached to one bilirubin molecule, hence the compound name bilirubin diglucuronide which is generally referred to as conjugated bilirubin 6.

Two Forms of Bilirubin

The two forms of bilirubin in the body are: indirect reacting, lipid- soluble, unconjugated bilirubin, which is protein (albumin) bound; and direct reacting, water-soluble conjugated bilirubin, which circulates freely in the blood until it reaches the liver, where it is conjugated with glucuronide transferase enzyme and then excreted into the bile 2,3,4. Unconjugated bilirubin is lipophilic and thus has a high affinity for brain tissue. Bilirubin encephalopathy is an acquired condition caused by extreme unconjugated hyperbilirubinemia which exceeds the capacity of plasma albumin to bind bilirubin, and thus keep it from crossing the blood-brain barrier 5. In the central nervous system bilirubin may be neurotoxic causing irreversible damage of neurons in the basal ganglia ad cerebellum 4.

200-250 mg of bilirubin is excreted in the bile each day. About 90% of it is excreted in the feces. In the gut, bacteria break bilirubin down into the colorless compound stercobilinogen, which is partially oxidized into stercobilin, the brown compound that colors the stools. About 1% reaches the systemic circulation and is excreted by the kidneys as urobilinogen. The renal excretion increases when the liver is damaged 3.

Bilirubin-associated Disorders

An increase in unconjugated bilirubin is associated with increased destruction of red blood cells (RBCs). An increase in free-flowing bilirubin is frequently associated with liver blockage. Excess bilirubin (hyperbilirubinemia) within cells and tissues causes jaundice, or yellowing of the skin, sclerae and mucous membranes. Hyperbilirubinemia occurs with destruction of red blood cells, diseases affecting metabolism and excretion of bilirubin in the liver, and diseases that cause destruction of the bile duct. The measurement of bilirubin allows evaluation of liver function and hemolytic anemias 1,2.

  1. Sue E. Huether, RN, PhD, Kathryn L. McCance, RN, PhD. Understanding Pathophysiology.
  2. Frances Talaska Fischbach, Marshall Barnett Dunning. A Manual of Laboratory and Diagnostic Tests
  3. Stefan Silbernagl, Agamemnon Despopoulos. Color Atlas of Physiology
  4. Henryk Dancygier. Clinical Hepatology: Principles and Practice of Hepatobiliary Diseases, Volume 1
  5. Larry R. Engelking. Textbook of Veterinary Physiological Chemistry
  6. Howard J. Worman. The Liver Disorders And Hepatitis Sourcebook