What is Conjugated Bilirubin?
Conjugated bilirubin is the water-soluble form of bilirubin created in hepatocytes through glucuronidation by the enzyme glucuronyltransferase, which allows it to be excreted into bile and ultimately eliminated from the body. 1
Biochemical Formation and Structure
Conjugated bilirubin is produced when unconjugated bilirubin (which is lipophilic and albumin-bound) undergoes hepatic processing in the liver. 1
The conjugation process involves the enzyme UDP-glucuronyltransferase (UGT1A1) in the endoplasmic reticulum of hepatocytes, which attaches glucuronic acid molecules to bilirubin. 2
A single bilirubin molecule reacts with two molecules of glucuronic acid to form bilirubin diglucuronide, the predominant form in bile, though monoconjugated forms also exist. 3, 4
This glucuronidation reaction is energy-producing, releasing approximately -22 kCal/mol, which may serve as a responsive mechanism during hepatic damage. 3
Key Functional Differences from Unconjugated Bilirubin
The critical distinction is that conjugated bilirubin is water-soluble, unlike unconjugated bilirubin, which enables its excretion in urine when blood levels are elevated. 5
Unconjugated bilirubin cannot be directly excreted and requires hepatic processing, whereas conjugated bilirubin can be eliminated through bile and, when elevated in blood, through urine. 1
Only conjugated bilirubin appears in urine because unconjugated bilirubin is bound to albumin and cannot be filtered by the kidneys. 5
Transport and Excretion Mechanisms
After conjugation, bilirubin glucuronides are transported across the hepatocyte canalicular membrane into bile by the transporter MRP2 (multidrug resistance-associated protein 2). 2
A substantial fraction of conjugated bilirubin is also secreted by MRP3 at the sinusoidal membrane back into blood, where it is reuptaken by OATP1B1 and OATP1B3 transporters, creating a liver-blood cycling system. 6
This cycling mechanism explains why conjugated hyperbilirubinemia can persist even after resolution of the underlying cause, as delta bilirubin (albumin-bound conjugated bilirubin) has a 21-day half-life. 5
Clinical Significance of Elevated Conjugated Bilirubin
Conjugated hyperbilirubinemia (where conjugated bilirubin represents >35% of total bilirubin) indicates parenchymal liver disease or biliary obstruction, requiring prompt diagnostic evaluation. 5
Common causes include viral hepatitis, alcohol-induced liver disease, autoimmune hepatitis, primary biliary cholangitis, medication-induced liver injury, and biliary tract obstruction from stones or malignancy. 5
In neonates, conjugated bilirubin >25 μmol/L requires urgent pediatric assessment for possible liver disease, as physiological jaundice in newborns involves unconjugated bilirubin only. 1
Important Laboratory Considerations
Most laboratories report "direct bilirubin," which includes both conjugated bilirubin and delta bilirubin (albumin-bound conjugated bilirubin), not just conjugated bilirubin alone. 5, 1
Delta bilirubin's prolonged half-life can cause persistent hyperbilirubinemia even after the underlying liver disease has resolved, and fractionation may be needed to distinguish these components. 5
In adults with significant liver disease, the conjugated fraction should predominate over unconjugated bilirubin. 1