Difference between Conjugated and Unconjugated Bilirubin

Bilirubin is a yellow-coloured pigment and a metabolite of heme. It is formed when the haemoglobin of red blood cells undergoes breakdown (heme degradation). There are two types of bilirubin, conjugated and unconjugated bilirubin.

When the total bilirubin increases above 30 to 35 mmol/l, it leads to the buildup of bilirubin in the tissues. This building up of bilirubin leads to jaundice, a condition causing yellowing skin, sclera and mucous membranes. An increased bilirubin level in the body may indicate a liver condition or damage. Keep reading this blog to learn more about conjugated and unconjugated bilirubin and their differences.

What is Unconjugated Bilirubin?

Unconjugated bilirubin is otherwise also known as indirect bilirubin. 

  1. Unconjugated bilirubin is formed during the breakdown process of heme. 
  2. Unconjugated bilirubin is water-insoluble and is extremely toxic to the body. 
  3. The normal value for unconjugated bilirubin in adults should be in 0.2 to 0.8 mg/dL. If unconjugated bilirubin is present in the body in larger quantities, then it may cause damage to the brain. 
  4. Unconjugated bilirubin is absent in the bile. 
  5. It needs to be converted into conjugated bilirubin so it can be excreted from the body. 
  6. Indirect bilirubin levels can be maintained by 
    1. Staying hydrated
    2. Including lots of fruits and vegetables in the diet 
    3. Avoiding alcohol intake 

High Levels of Unconjugated Bilirubin

High unconjugated bilirubin levels in the plasma refer to unconjugated hyperbilirubinemia. Unconjugated hyperbilirubinemia can also cause jaundice in neonates. Various factors might be responsible for unconjugated hyperbilirubinemia. These include:

  1. An increase in the production of bilirubin or increased haemoglobin degradation.
  2. Impaired hepatic bilirubin uptake.
  3. Reduced or impaired conjugation of bilirubin.
  4. Having inherited disorders like hemolytic anaemia and Gilbert's syndrome.

What is Conjugated Bilirubin?

Conjugated bilirubin is otherwise also known as direct bilirubin. 

  1. Conjugated bilirubin is water soluble and is not toxic to the body.
  2. An adult's normal value of conjugated bilirubin should be between 0.0 to 0.3 mg/dL. 
  3. Since conjugated bilirubin is water soluble, it can be filtered by the kidney.
  4. Conjugate bilirubin is formed when unconjugated bilirubin is conjugated by adding glucuronic acid. 
  5. Normally, conjugated bilirubin is not present in the urine. However, in certain conditions or diseases, it may be seen in the urine. The presence of conjugated bilirubin in the urine will give it a dark cola or tea-like colour (brown). 

High Levels Conjugated Bilirubin Causes

Elevating the conjugated bilirubin level leads to conjugated hyperbilirubinemia. Various causes lead to an increase in the level of conjugated bilirubin. Some of these causes of conjugated hyperbilirubinemia include:

  1. Cholelithiasis
  2. Viral hepatitis  
  3. Liver cirrhosis 
  4. Certain medications and toxins
  5. Sepsis 
  6. Alcohol 
  7. Autoimmune disorders 
  8. Certain metabolic diseases like Gaucher disease, Niemann-Pick disease, etc.

Difference between Conjugated and Unconjugated Bilirubin

Parameter

Unconjugated Bilirubin Conjugated Bilirubin 
Alternative Name Indirect bilirubin Direct bilirubin 

Definition

Unconjugated bilirubin is the end product of heme degradation. Conjugated bilirubin is a conjugated form of unconjugated bilirubin. 

Enzyme catalysis the production

Biliverdin reductase catalyses the production of unconjugated bilirubin.  Uridine diphosphate (UDP) - glucuronyl transferase is the enzyme catalysing the production of conjugated bilirubin. 

Solubility profile 

Insoluble in water  Soluble in water 

Toxicity profile 

It is toxic for the human body It is non-toxic for the human body 

Protein (albumin) carrier 

Unconjugated bilirubin requires binding itself to albumin to move in the bloodstream.  Conjugated bilirubin does not require binding to the protein carrier albumin to move across the bloodstream. 

Molecular weight 

High molecular weight. Hence, it is not filtered by the kidney.  Small molecular weight. Hence, it is filtered by the kidney.

Bile presence 

Not present in the bile  Present in the bile

Key facts

  1. An impairment in bilirubin conjugation can be caused due to hereditary conditions like Gilbert's syndrome and the Crigler-Najjar syndrome type I and II.
  2. Many newborns develop Neonatal hyperbilirubinemia due to breastfeeding. This is because breastfeeding increases the level of unconjugated bilirubin in the baby. This condition is otherwise also called breast milk jaundice or breastfeeding jaundice.

Takeaway

To summarise the differences between conjugated and unconjugated bilirubin:

  1. Bilirubin is a yellow-coloured substance and a metabolite of heme. There are two types of bilirubin, conjugated and unconjugated bilirubin. An increase in the level of bilirubin in the body and its buildup in the tissues may indicate liver condition or damage. 
  2. Building up of bilirubin leads to jaundice. Hence, symptoms like yellowing skin, sclera or a dark urine colour must not be ignored. 

You must immediately consult a doctor if you notice any such symptoms related to high levels of conjugated and unconjugated bilirubin. Our experts will help manage your condition at the right time! So visit HexaHealth to get the best treatment for your conditions!

Frequently Asked Questions

What is the role of bilirubin?

The role of bilirubin in the body includes: 

  1. Bilirubin helps in the excretion of unwanted heme
  2. Bilirubin may help protect against cardiovascular diseases (CVD) by decreasing oxidative stress.

What is conjugated bilirubin?

Conjugated bilirubin or direct bilirubin is a conjugated form of unconjugated bilirubin, produced when unconjugated bilirubin, along with glucuronic acid, gets conjugated by the action of the enzyme uridine diphosphate (UDP) - glucuronyl transferase.

What is unconjugated bilirubin?

Unconjugated bilirubin or indirect bilirubin. Unconjugated bilirubin is produced when biliverdin undergoes reduction by the enzyme biliverdin reductase.

What is the difference between conjugated and unconjugated bilirubin?

There are differences between conjugated and unconjugated bilirubin, like:

  1. Unconjugated bilirubin is insoluble in water, whereas conjugated bilirubin is soluble in water.
  2. Unconjugated bilirubin requires the protein carrier (albumin) to move in the bloodstream, but conjugated bilirubin does not require the protein carrier for its movement across the bloodstream.
  3. Unconjugated bilirubin is toxic for the human body; however, conjugated bilirubin is non-toxic for the human body.

What happens if conjugated and unconjugated bilirubin is raised?

Suppose the levels of conjugated and unconjugated bilirubin are raised. In that case, it might indicate potential damage to the liver, or it might be a sign that the liver functioning is abnormal. Thus leading to a medical condition known as hyperbilirubinemia.

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