What is the Difference Between Direct and Indirect Bilirubin

The main difference between direct and indirect bilirubin is that direct bilirubin is transported in the blood in free form, whereas indirect bilirubin is transported bound to albumin.

Direct and indirect bilirubin are two bilirubin forms that occur in the blood. Bilirubin is a yellow pigment produced in the hemoglobin breakdown. Also, direct bilirubin is called conjugated bilirubin, while indirect bilirubin is called unconjugated bilirubin. 

Key Areas Covered

1. What is Direct Bilirubin
– Definition, Facts, Importance
2. What is Indirect Bilirubin
– Definition, Facts, Importance
3. Similarities Between Direct and Indirect Bilirubin
– Outline of Common Features
4. Difference Between Direct and Indirect Bilirubin
– Comparison of Key Differences

Key Terms  

Direct Bilirubin, Indirect Bilirubin

What is Direct Bilirubin

Direct or conjugated bilirubin is the water-soluble form of bilirubin processed in the liver. Also, unconjugated bilirubin undergoes chemical reactions in the liver to form conjugated bilirubin. It is conjugated with glucuronic acid. Direct bilirubin is excreted through feces. Importantly, it is a marker of liver function. Therefore, it can be used to diagnose liver and gallbladder diseases.

Figure 1: Bilirubin

What is Indirect Bilirubin

Indirect or unconjugated bilirubin is a fat-soluble pigment, a product of the breakdown of hemoglobin in red blood cells. Also, it is transported to the liver and binds to albumin. Inside the liver, it is metabolized to unconjugated bilirubin. Importantly, indirect bilirubin is not water-soluble and accumulates in the body. However, it is toxic to the body. Jaundice and other symptoms occur in high levels of indirect bilirubin.

Figure 2: Accumulation of Bilirubin in the Liver

Moreover, total bilirubin in the body is the sum of direct and indirect bilirubin. Normal total bilirubin levels of the body are 0.3 to 1.9 mg/dL. Also, the normal direct bilirubin level is 0.3 mg/dL. In addition, the level of normal indirect bilirubin is the difference between total and direct bilirubin.  

Similarities Between Direct and Indirect Bilirubin

• Direct and indirect bilirubin are two bilirubin forms that occur in the blood.
• They are the breakdown products of hemoglobin.

Difference Between Direct and Indirect Bilirubin

Definition

Direct bilirubin is the form of bilirubin that has been conjugated with glucuronic acid and excreted in the bile. In contrast, indirect bilirubin is the difference between total and direct bilirubin.

Significance

Direct bilirubin is the processed, water-soluble form of bilirubin excreted in the urine, while indirect bilirubin is the initial form of bilirubin produced in the breakdown of red blood cells. 

Also Called as

Direct bilirubin is also called conjugated bilirubin, while indirect bilirubin is called unconjugated bilirubin. 

Chemical Composition

Direct bilirubin is water-soluble and less lipid-soluble, while indirect bilirubin is water-insoluble and lipid-soluble. 

Transport in Blood

Direct bilirubin is transported in the blood in the free form, while indirect bilirubin is transported bound to albumin.

Ability to Pass through the Blood-Brain Barrier

Direct bilirubin does not pass through the blood-brain barrier, while indirect bilirubin passes through the blood-brain barrier and causes neurotoxicity. 

Urinary Excretion

Direct bilirubin is excreted in urine, while indirect bilirubin is not excreted in urine. 

Color

Direct bilirubin does not contribute to yellow coloration, while indirect bilirubin is responsible for the yellow color of bruises and jaundice.

Clinical Significance

Direct bilirubin increases in obstructive jaundice and biliary atresia, while indirect bilirubin increases in elevated hemolytic anemia and Gilbert’s syndrome. 

Conclusion

In brief, direct and indirect bilirubin are two bilirubin forms that occur in the blood. Direct or conjugated bilirubin is the processed form of bilirubin and is water-soluble. Also, it is transported in the free form in the blood. Finally, it is excreted in urine. However, it does not contribute to the yellow coloration. In comparison, indirect or unconjugated bilirubin is the water-soluble form of bilirubin formed by the breakdown of hemoglobin. It is transported in the blood bound to albumin. But it is not excreted in urine. Importantly, it causes the yellow coloration. Therefore, the main difference between direct and indirect bilirubin is the method of transportation in blood. 

References:

1. Kalakonda A, Jenkins BA, John S. Physiology, Bilirubin. [Updated 2022 Sep 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. 

Image Courtesy:

1. “Structure of bilirubin” By LHcheM – Own Work (CC-BY SA 3.0) via Commons Wikimedia
2. “Bilirubin pigment in cholestatic liver” By Department of Pathology, Calicut Medical College – Own work (CC-BY SA 4.0) via Commons Wikimedia