Difference between Direct and Indirect Bilirubin

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Jasmine Grover

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Bilirubin is a yellowish pigment that is formed as a result of the catabolism of haemoglobins.

It is processed in the liver and then excreted in the bile, which helps to digest fats in the small intestine. Bilirubin is mostly found in the liver.

  • Bilirubin is a yellow pigment made when old red blood cells break down.
  • Bilirubin levels in the blood are measured to diagnose various liver and blood disorders. 
  • High bilirubin levels in the blood can cause jaundice causing a yellowing of the skin and eyes.
  • It is formed from the reduction of biliverdin, which is produced when porphyrin rings in haemoglobin are cleaved by oxidation.
  • Its main role is as an antioxidant that protects the brain by neutralizing free superoxide molecules.
  • In the liver, bilirubin is divided into two forms: direct and indirect bilirubin.

Key Terms: Direct bilirubin, indirect bilirubin, blood disorders, porphyrin, haemoglobin, oxidation, direct bilirubin vs indirect bilirubin

Read More: Antibodies and antigens


Direct Bilirubin

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Direct bilirubin is the modified, less toxic form of bilirubin obtained after the conjugation with glucuronic acid.

  • Enzyme glucuronyltransferase is responsible for the conjugation of bilirubin with glucuronic acid.
  • Direct bilirubin is soluble in water and easy to excrete from the body.
  • The total bilirubin in the body is the sum of direct and indirect bilirubin.
  • Direct bilirubin is soluble in water and can be measured in the blood to help diagnose liver and blood disorders. 
  • The normal levels of bilirubin in adults range from 0.3 to 1.9 mg/dL.
  • However, the value of direct bilirubin present is from 0.0 to 0.3 mg/dL

Indirect Bilirubin

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Indirect bilirubin or unconjugated bilirubin is a byproduct of breaking down haemoglobin.

  • It attaches to albumin to transport from blood to the liver
  • But this form of bilirubin is toxic and hence converted to direct bilirubin in the liver.
  • Indirect bilirubin is soluble in lipids and insoluble in water.
  • Symptoms of high indirect bilirubin levels can include yellowing of the skin and eyes (jaundice), fatigue, and abdominal pain.
  • High levels may be caused by conditions like haemolytic anaemia or genetic malfunctioning.

Read More: Red blood cells (RBCs) & white blood cells (WBCs)


Levels of Bilirubin

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Bilirubin is a pigment that is produced when red blood cells break down. While lower levels of bilirubin are not a concern for the human body, higher levels can pose a risk and require medical attention.

  1. Hyperbilirubinemia

Very high levels of bilirubin can cause a condition called hyperbilirubinemia. It includes a buildup of bilirubin in the blood and can cause various health problems. High levels of bilirubin can damage brain tissues and lead to seizures. The reasons for high bilirubin levels include haemolysis, Gilbert’s syndrome, Rotor syndrome, consumption of specific drugs, etc. 

  1. Jaundice

Another disease caused by high levels of bilirubin is jaundice. Jaundice causes the yellowing of the eyes, skin, and mucous membranes. It is caused by several factors, such as gallstones, tumours, and hepatitis.

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Direct vs Indirect Bilirubin

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The differences between direct and indirect bilirubin are as follows - 

Direct Bilirubin Indirect Bilirubin
Direct bilirubin is a conjugated form of bilirubin obtained by the catabolism of haemoglobin. Indirect bilirubin is a direct result of the catabolism of haemoglobin.
Direct Bilirubin is also known as conjugated bilirubin Indirect Bilirubin is also known as unconjugated bilirubin
It is water soluble and can be excreted in the bile It is not water-soluble and cannot be excreted in the bile
Direct bilirubin is formed when bilirubin is processed by the liver Indirect Bilirubin is formed when red blood cells break down
Its elevated levels can be a sign of liver damage or obstruction of the bile ducts Its elevated levels can be a sign of hemolytic anaemia or other conditions that cause excessive destruction of red blood cells
Direct bilirubin does not require any protein carrier for transportation. It transports from blood to the liver by binding to albumin.
The normal range is typically 0.0-0.3 mg/dL The normal range is typically 0.2-0.8 mg/dL

Things to Remember

  1. Bilirubin is a yellowish pigment formed from the breakdown of red blood cells that can accumulate in the blood 
  2. Direct bilirubin is water-soluble and can be excreted in the bile, while indirect bilirubin is not water-soluble and cannot be excreted in the bile. 
  3. Direct bilirubin is formed when bilirubin is processed by the liver and elevated levels can be a sign of liver damage or bile duct obstruction. 
  4. Indirect bilirubin is formed when red blood cells break down. 
  5. Direct bilirubin can be measured directly in a blood test, while indirect bilirubin levels must be calculated by subtracting direct bilirubin from total bilirubin.

Read More: Plasma


Sample Questions

Ques. What causes high bilirubin? (3 marks)

Ans. High bilirubin levels can be caused by various factors, including hemolytic anemia, liver damage or disease, obstruction of the bile ducts, Gilbert's syndrome, Crigler-Najjar syndrome, and certain medications. 

Hemolytic anemia and liver disease are the most common causes of high bilirubin levels, as they result in an increased breakdown of red blood cells and a decreased ability of the liver to process and excrete bilirubin.

Ques. What is the function of bilirubin in the liver? (3 marks)

Ans. In the liver, bilirubin is conjugated with glucuronic acid to form a water-soluble bilirubin glucuronide. 

  • This conjugated bilirubin is then excreted in the bile and eliminated from the body. 
  • The function of bilirubin in the liver is to act as a waste product of the breakdown of red blood cells and to be eliminated from the body through the bile. 
  • Bilirubin has antioxidant properties that help protect the liver from damage caused by free radicals and oxidative stress.

Ques. Which bilirubin is most important? (3 marks)

Ans. Both direct (conjugated) and indirect (unconjugated) bilirubin are important, but elevated levels of indirect bilirubin are typically more clinically significant than elevated levels of direct bilirubin. This is because indirect bilirubin is not water-soluble and cannot be excreted in the bile, leading to the accumulation of bilirubin in the blood and tissues, which can result in jaundice and other complications. Elevated levels of direct bilirubin can also be a sign of liver disease or obstruction of the bile ducts, but they are usually less severe and more easily treatable than elevated levels of indirect bilirubin.

Ques. What is bilirubin, and how is it formed in the body? (5 marks)

Ans. Bilirubin is a yellowish-orange pigment that is formed from the breakdown of heme, a component of hemoglobin found in red blood cells. 

  • When red blood cells reach the end of their lifespan, they are removed from circulation and broken down by macrophages in the spleen, liver, and bone marrow. 
  • The heme component of hemoglobin is converted to bilirubin, which is then released into the bloodstream and transported to the liver. 
  • In the liver, bilirubin is conjugated with glucuronic acid to form a water-soluble bilirubin glucuronide, which is then excreted in the bile and eliminated from the body. 
  • Bilirubin gives urine its yellow color and is responsible for the yellow color of bruises and the yellowing of the skin and eyes in conditions like jaundice.

Ques. What are the causes of hyperbilirubinemia, and what are the associated symptoms? (5 marks)

Ans. Hyperbilirubinemia is a condition characterized by high levels of bilirubin in the blood, which can occur due to various causes. The common causes of hyperbilirubinemia include:

  • Increased breakdown of red blood cells, which can occur due to blood transfusion reactions, sickle cell anemia, or other blood disorders.
  • Damage or disease of the liver, such as hepatitis, cirrhosis, or liver cancer.
  • Blockage of the bile ducts due to gallstones, tumors, or other conditions.
  • Gilbert's syndrome or Crigler-Najjar syndrome, which affect the way the body processes bilirubin.
  • Certain medications, such as rifampin, sulfonamides, and some chemotherapy drugs, can also increase bilirubin levels in some people.

The symptoms of hyperbilirubinemia depend on the underlying cause and the severity of the condition. Common symptoms include:

  • Yellowing of the skin and eyes (jaundice)
  • Dark urine
  • Pale stools
  • Fatigue and weakness
  • Abdominal pain and swelling
  • Nausea and vomiting
  • Itching (pruritus)
  • Fever
  • Weight loss
  • Severe cases of hyperbilirubinemia can cause complications such as liver failure, brain damage, and death.

Ques. What is the relationship between bilirubin and liver disease? (5 marks)

Ans. Bilirubin and liver disease are closely related because the liver is the primary organ responsible for processing bilirubin and eliminating it from the body. 

  • Liver disease can interfere with the normal processing and elimination of bilirubin, leading to a buildup of bilirubin in the blood and tissues, which can result in jaundice and other symptoms.
  • Liver disease can also cause damage to the liver cells, which can impair their ability to produce and secrete bilirubin. 
  • This can result in a decrease in the levels of bilirubin in the blood, a condition known as hypobilirubinemia. 
  • In some cases, liver disease can also cause a mixed pattern of hyperbilirubinemia and hypobilirubinemia.

The relationship between bilirubin and liver disease is complex, and the exact mechanisms that lead to bilirubin-related complications in liver disease are not fully understood. However, measuring bilirubin levels in the blood is an important tool for diagnosing and monitoring liver disease, and treating the underlying liver disease can help improve bilirubin metabolism and elimination.

Ques. What are the normal levels of bilirubin in the blood? (3 marks)

Ans. The normal levels of bilirubin in the blood can vary depending on the laboratory that performs the test and the method used for measuring bilirubin. However, in general, the normal total bilirubin level in the blood is less than 1.2 milligrams per deciliter (mg/dL) for adults.

Within the total bilirubin, there are two types of bilirubin: direct (conjugated) and indirect (unconjugated) bilirubin. The normal levels of direct bilirubin are typically less than 0.3 mg/dL, while the normal levels of indirect bilirubin are less than 0.9 mg/dL.

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