What are the different types of bilirubin (a yellow compound that occurs in the normal catabolic pathway that breaks down heme in red blood cells)?

From the Guidelines

Bilirubin exists in two main forms: unconjugated and conjugated bilirubin, with total bilirubin representing the sum of both forms. These forms are crucial in understanding liver function and diagnosing various conditions.

Types of Bilirubin

• Unconjugated bilirubin is the insoluble form that is transported to the liver for conversion into soluble conjugated bilirubin, which can then be excreted 1.
• Conjugated bilirubin is the soluble form that is excreted in bile and eventually eliminated in stool.
• Total bilirubin is the sum of both unconjugated and conjugated bilirubin, and elevations in either fraction can lead to an increase in the measured bilirubin concentration 1.

Clinical Significance

• Elevated unconjugated bilirubin typically indicates increased red blood cell breakdown or liver uptake problems, such as in hemolytic anemia or Gilbert’s syndrome 1.
• Elevated conjugated bilirubin usually suggests liver excretion issues or bile duct obstruction, such as in parenchymal liver disease or biliary obstruction 1.
• In the neonatal period, a physiological increase in total bilirubin, which is unconjugated, may be seen, but this can be pathological if high or prolonged 1.

Diagnosis and Management

• Measuring the levels of unconjugated and conjugated bilirubin can help diagnose conditions such as Gilbert’s syndrome, hemolytic anemia, and liver disease 1.
• In cases where the majority of the elevated bilirubin comprises the unconjugated fraction, the cause is virtually always Gilbert’s syndrome, and patients can be reassured 1.
• Referral to a pediatrician for urgent assessment of possible liver disease is essential in neonates and infants with conjugated bilirubin >25 μmol/L 1.

From the Research

Types of Bilirubin

There are several types of bilirubin, including:

• Unconjugated bilirubin: this type of bilirubin is not water-soluble and requires conversion to a water-soluble form for excretion 2
• Conjugated bilirubin: this type of bilirubin is water-soluble and can be excreted in the bile 2
• Delta-bilirubin: this type of bilirubin is covalently bound to albumin and is estimated by subtracting the sum of unconjugated and conjugated bilirubin from the concentration of total bilirubin 2
• Bilirubin-monoglucuronide: this type of bilirubin is a conjugated form of bilirubin that contains one glucuronide molecule 3
• Bilirubin-diglucuronide: this type of bilirubin is a conjugated form of bilirubin that contains two glucuronide molecules 3

Measurement of Bilirubin Types

The different types of bilirubin can be measured using various methods, including:

• Coated thin films to measure unconjugated, conjugated, and total bilirubin 2
• Diazo-based thin films to measure total bilirubin 2
• High-performance liquid chromatography (HPLC) to measure unconjugated bilirubin, bilirubin-monoglucuronide, bilirubin-diglucuronide, and delta-bilirubin 3