Bilirubin is formed in the reticuloendothelial cells by the breakdown of hemoglobin. The sequence of events is hemoglobin → hematin → protporphyrin → biliverdin → bilirubin.1 Bilirubin is released from the reticuloendothelial cells into the blood in the free or unconjugated form and travels attached to albumin or αglobulin which keep it in solution. It is not excreted by the kidneys.
The liver converts bilirubin to the water-soluble form by conjugating it with glucuronide, sulfate, or other groups. In this respect the liver handles bilirubin as it does a host of other compounds that it detoxifies or solubilizes by its conjugating mechanisms. Examples are corticosteroids, estrogens, thyroxin, epinephrine, morphine, and iopanoic acid (Telepaque). About 80% of the bilirubin is conjugated with glucuronide, 10% with sulfate, and the rest with other compounds. Glucuronide conjugation is thus the most important, but not the only mechanism for solubilizing bilirubin. Bilirubin conjugates are
Zieve L. Jaundice in Cirrhosis. JAMA. 1965;191(6):475-479. doi:10.1001/jama.1965.03080060049009