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Precautions

  1. Avoid hemolysis.
  2. Avoid shaking of the tube that may lead to inaccurate results.
  3. Do not expose the tube to light. Exposure to light like the sun or even artificial light may decrease the value.
  4. If there is a delay in the test then keep the sample away from the light and refrigerate it.

Purpose of the test (Indications)

  1. For the diagnosis of jaundice.
  2. To differentiate different types of jaundice.
  3. For the follow-up of a patient with treatment.
  4. To assess the progress of the disease.
  5. This test is done to evaluate the liver functions.
  6. This is done in a patient with hemolytic anemia in adults.
  7. It is also done to evaluate the hemolytic anemia in the newborn.

Pathophysiology

  1. Raised Bilirubin is the indicator of liver dysfunction.
  2. Basically, this is the end product of Hemoglobin metabolism.
  3. Bilirubin is one component of bile which is transported from liver and stored in the gallbladder and from there delivered to the intestine.
  4. Bile is formed in the liver and it consists of Bile salts, phospholipids, cholesterol, bicarbonate, bilirubin and water.
  5. Further metabolism of bilirubin takes place in the intestine.
  6. Most of it is metabolized in the intestine and excreted in feces.
  7. The increased amount of the bilirubin causes the yellow color of the skin and conjunctiva ( Jaundice ).
  8. The bilirubin which is not conjugated to the liver, attach to albumin (carrying protein )is called Indirect bilirubin.
  9. The bilirubin conjugate with the glucuronic acid. This process takes place in the liver and gives rise to conjugated or direct bilirubin. Now conjugated bilirubin is no more bound to protein.

 

  1. Direct bilirubin + Indirect bilirubin = Total bilirubin.
  2. Indirect bilirubin  is calculated as follows: 
  3. Indirect bilirubin = Total bilirubin – direct bilirubin
    1. Hemoglobin from RBC is released and form Heme and Globin.
    2. Heme is metabolized to Biliverdin and this is transformed into bilirubin.

  1. Jaundice appears when the bilirubin level is above 2.5 mg/dl.
  2. In the newborn when the liver can not conjugate bilirubin and if the level increases then this indirect bilirubin can cross the blood-brain barrier and leads to toxic injury to the brain and called Kernicterus.
  3. If bilirubin level exceeds 15 mg/dl then immediately start the treatment to avoid the brain damage.
  4. While physiologic jaundice appears after 3 to 4 days and subsidies itself.

Normal adult values

Another source Total bilirubin level

Age Premature  mg/dL Full-term   mg/dL Adult   mg/dL
Cord blood <2 mg <2.0  
0 to 1 day <8.0 1.4 to 8.7  
1 to 2 days <12.0 3.4 to 11.5  
3 to 5 days <16.0 1.5 to 12.0  
5 days to 60 years     0.3 to 1.2
60 to 90 year     0.2 to 1.1
>90 year     0.2 to 0.9

Physiologic jaundice of the newborn:

Bilirubin above 15 mg /dl in newborn needs immediate treatment.

Raised Bilirubin level is seen in:

  1. Some infections, such as an infected gallbladder, or cholecystitis.
  2. Some inherited diseases, such as Gilbert’s syndrome. Although jaundice may occur in some people with Gilbert’s syndrome, the condition is not harmful.
  3. Diseases that cause liver damage, such as hepatitis, cirrhosis, or mononucleosis.
  4. Diseases that cause blockage of the bile ducts, such as gallstones or cancer of the pancreas.
  5. Rapid destruction of red blood cells in the blood, such as from sickle cell disease or an allergic reaction to blood received during a transfusion (called a transfusion reaction).
  6. Medicines that may increase bilirubin levels. This includes many antibiotics, some types of birth control pills, indomethacin (Indocin), phenytoin (Dilantin), diazepam (Valium), and flurazepam (Dalmane).

Decreased Bilirubin level is seen in:

  1. Medicines that may decrease bilirubin levels. This includes vitamin C (ascorbic acid), phenobarbital, and theophylline.

Bilirubin levels that may require treatment in a full-term, healthy baby:

  1. 24 hours or younger infant need treatment when bilirubin level is More than 10 mg/dL or more than 170 mmol/L.
  2. 25 to 48 hours infant need treatment when bilirubin is more than 15 mg/dL or more than 255 mmol/L.
  3. 49 to 72 hours infant needs treatment when bilirubin is more than 18 mg/dL or more than 305 mmol/L
  4. Older than 72 hours of infant needs treatment when the bilirubin level is more than 20 mg/dL or more than 340 mmol/L

Causes of direct hyperbilirubinemia:

Causes of Indirect hyperbilirubinemia:

Types of jaundice may be of following types.

  1. Pre-hepatic jaundice. The etiology is before the liver like increased hemolysis of RBC.
  2. Hepatic jaundice. Now the causes are in the liver like hepatitis.
  3. Post-hepatic jaundice. Where the cause is after the liver like gallstone, cancers and these are the obstructive type of jaundice.

Table showing the Different type of Jaundice and their causes

Type of Jaundice Causes Pathophysiology

Unconjugated

hyperbilirubinemia

Extravascular hemolysis Heme is converted to unconjugated bilirubin
 

Right heart failure and Cirrhosis

There is a defect in the delivery of unconjugated bilirubin to liver
 

Hypothyroidism and Crigler-Najjar syndrome

There is a defect in the conjugation of bilirubin in the hepatocytes
 

Drugs like Rifampicin  and Gilbert syndrome

There is a defect in the uptake of unconjugated bilirubin into hepatocytes

Conjugated 

hyperbilirubinemia

Mechanical obstruction by tumors, stones or strictures, and primary biliary cirrhosis

There is a defect in the flow of conjugated bilirubin through canaliculi and bile ducts. Called cholestatic jaundice.
 

Drugs like estrogen and cyclosporine

Dubin-Johnson syndrome

Pregnancy

There is a defect in the transmembrane secretion of conjugated bilirubin into the canaliculus. This is also called hepatocellular jaundice 

  Sepsis Like above

Possible References Used

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