From the Guidelines
Except in the neonatal period, the majority of measurable bilirubin should be conjugated, even in individuals with significant liver disease. This is based on the guidelines on the management of abnormal liver blood tests published in the journal Gut in 2018 1.
Key Points
- Bilirubin exists in two forms: unconjugated and conjugated, with the latter being the predominant form in most cases outside of the neonatal period.
- The liver converts unconjugated bilirubin into conjugated bilirubin for excretion, and any elevation in total bilirubin can be due to increases in either fraction.
- In adults and children beyond the neonatal period, conjugated bilirubin typically makes up the majority of total bilirubin, as stated in the guidelines 1.
Clinical Implications
- The distinction between unconjugated and conjugated hyperbilirubinemia is crucial for diagnosing the underlying cause of elevated bilirubin levels.
- Unconjugated hyperbilirubinemia is often associated with hemolysis or impaired conjugation, such as in Gilbert’s syndrome, whereas conjugated hyperbilirubinemia suggests parenchymal liver disease or biliary obstruction 1.
- In clinical practice, understanding the predominant form of bilirubin can guide further diagnostic workup and management, emphasizing the importance of differentiating between unconjugated and conjugated bilirubin.
From the Research
Bilirubin Conjugation
- Bilirubin is taken up from blood into hepatocytes by sinosuidal membrane transporters and then excreted into bile through the bile canalicular membrane mainly as bilirubin glucuronides 2.
- In the liver, bilirubin is conjugated with UDP-glucuronate, making it water-soluble diglucuronide 3.
- The conjugation of bilirubin with glucuronic acid is an energy-consuming reaction, with an energy change of -22 kCal/mol per molecule 3.
Unconjugated vs Conjugated Bilirubin
- Unconjugated bilirubin may accumulate in plasma and be taken up by other lipid-containing tissues, collagen, and brain tissue if the rate of production is excessive or an infant's capacity to conjugate and excrete the pigment is deficient 4.
- Conjugated bilirubin, on the other hand, is excreted into bile by multidrug resistance-associated protein 2 (MRP2) 2.
- There is no direct evidence to suggest that most bilirubin is conjugated, but the process of conjugation is an important step in the metabolism and excretion of bilirubin 2, 3.
Clinical Relevance
- Hyperbilirubinemia can cause damage to the central nervous system, including kernicterus and bilirubin encephalopathy 4, 5.
- The management of neonatal hyperbilirubinemia includes phototherapy, exchange transfusion, and stimulation of liver conjugating enzymes 4, 5.
- Understanding the molecular mechanism of hepatocyte bilirubin transport and its clinical relevance is important for the development of new treatments for hyperbilirubinemia 2.