Key Difference – Direct vs Indirect Bilirubin
 

Bilirubin is the catabolic product of haemoglobin. Bilirubin exists in two main forms; conjugated and unconjugated bilirubin. The metabolism of bilirubin takes place predominantly in the liver. Bilirubin enters the liver in the unconjugated form and thereby converted to the conjugated form after some metabolic conversions. The conjugated bilirubin is also referred as direct bilirubin, and unconjugated bilirubin is referred to as indirect bilirubin. Direct Bilirubin or the conjugated form of bilirubin is covalently modified bilirubin that has increased solubility. This is due to the conjugation reaction with glucuronic acid, which takes place in the liver. Indirect Bilirubin is the type of bilirubin that is not attached or conjugated to any other chemical compound. Indirect bilirubin is bound to albumin, which is the common carrier protein of bilirubin. The key difference between the Direct and Indirect bilirubin is that direct bilirubin is the bilirubin that is conjugated with glucuronic acid while the indirect bilirubin is not conjugated to the liver and it attaches to the carrier protein albumin.

CONTENTS

1. Overview and Key Difference
2. What is Direct Bilirubin (or Conjugated Bilirubin)
3. What is Indirect Bilirubin (or Unconjugated Bilirubin)
4. Similarities Between Direct and Indirect Bilirubin
5. Side by Side Comparison – Direct vs Indirect Bilirubin in Tabular Form
6. Summary

What is Direct Bilirubin?

Direct bilirubin is covalently modified indirect bilirubin. This covalent modification is done to decrease the toxicity of bilirubin and to increase the solubility of bilirubin. Increasing the solubility of bilirubin makes it easy for the excretion process of bilirubin. The conjugation of bilirubin takes place with glucuronic acid as follows. UDP glucose is used as the starting compound for conjugation of bilirubin with glucuronic acid.

The normal levels of direct bilirubin lie in the range of 0.1 to 0.3 mg/dL or 1.0 to 5.1 mmol/L. If the serum direct bilirubin levels increase above the range, it is referred to as direct hyperbilirubinemia. The immediate causes of this are gallstones, gallbladder tumors, rotor syndrome, Dubin – Johnson syndrome, and certain drugs.

Figure 01: Formation of Direct Bilirubin

Genetic disorders and enzyme deficiencies can also lead to increased direct bilirubin levels in the serum. Direct bilirubin is combined with bile and is sent to the intestines, and is excreted. Although under hyperbilirubinemia conditions, bilirubin is excreted in the urine. Under this circumstance, the urine appears red.

What is Indirect Bilirubin?

Indirect bilirubin or unconjugated bilirubin is the immediate breakdown product of haemoglobin. This is the unmodified type of bilirubin. Under normal conditions, the serum indirect bilirubin levels should be around 0.2 to 0.7 mg/dL or 3.4 to 11.9 mmol/L.

Indirect bilirubin is soluble in lipids. Therefore, it is lipophilic. Indirect bilirubin is insoluble in water, and it is highly hydrophobic. Indirect bilirubin can cross the plasma membrane easily. The toxicity of indirect bilirubin is high, especially to the nervous system. Therefore, indirect bilirubin is converted to a more soluble, non-toxic form which is the conjugated form. Indirect albumin is associated with albumin, which is the main transport protein for bilirubin.

Increased level of indirect bilirubin in serum can be due to the several reasons such as increased RBC hemolysis (Erythroblastosisfetalis), conditions such as sickle cell anaemia, hepatitis, cirrhosis and due to the effect of some drugs etc.

What are the Similarities Between Direct and Indirect Bilirubin?

• Both are forms of bilirubin which are breakdown products of haemoglobin.
• Both function as biochemical compounds for liver tests.
• Increase in both components can lead to hyperbilirubinemia.

What is the Difference Between Direct and Indirect Bilirubin?

Summary – Direct vs Indirect Bilirubin

Direct and indirect bilirubin are the two forms of bilirubin in serum. They are measured as a part of the liver function test. Direct bilirubin is the more soluble, less toxic and is the conjugated form of bilirubin. Direct bilirubin is conjugated with glucuronic acid. Indirect bilirubin is the unconjugated form of bilirubin. It is highly toxic and is less soluble in water. Therefore, it is bound to albumin for transportation purposes. Increased direct and indirect bilirubin levels indicate metabolic disorders and diseases associated with the liver. This is the difference between direct and indirect bilirubin.

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Reference:

1.“Bilirubin -Part 1- Total, Direct and Indirect Bilirubin.” Bilirubin -Part 1- Total, Direct and Indirect Bilirubin | Labpedia.Net. Available here  
2.Indirect and direct bilirubin: origins, properties and metabolism. Available here

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