Conjugated (Direct) Bilirubin

Sample for Conjugated (Direct) Bilirubin

1. This test is done in the serum of the patient.
2. A random sample can be taken.
   1. This is ideal if the patient has nothing except water 4 to 8 hours before the sample.
3. The sample is stable at 4 °C for 3 days.
4. Protect the sample from the light because bilirubin is photo-oxidized (photosensitive).

Precautions for Conjugated (Direct) Bilirubin

1. Avoid hemolysis and lipemic serum, which will give a false result.
2. Avoid drugs that will increase the total bilirubin level like:
   1. Anabolic steroids.
   2. Antibiotics.
   3. Antimalarial drugs.
   4. Chlorpropamide.
   5. Methotrexate.
   6. Antihypertensive drug-like methyldopa.
   7. Oral contraceptives.
   8. Antituberculous drugs like rifampin.
3. Medications that will decrease the bilirubin level are:
   1. Penicillin.
   2. Caffeine.
   3. Barbiturates.
4. Exposure of the sample to sunlight or ultraviolet light may decrease the level.

Pathophysiology of Conjugated (Direct) Bilirubin

1. Conjugated hyperbilirubinemia is usually due to hepatocellular injury or cholestasis, intrahepatic or extrahepatic.
   1. Early diagnosis and management are carried out to prevent complications.
2. Bilirubin is yellow to a green pigment of bile derived from the porphyrin structure of hemoglobin.
   1. Excessive bilirubin within cells and the tissue causes skin jaundice (Icterus) or yellowness.
3. Bilirubin estimation is one of the liver function tests.
4. Clinically jaundice appears when the bilirubin level exceeds 2 mg/dl.

4.  Direct bilirubin dissolves in water (water-soluble) and is synthesized in the liver from indirect bilirubin.
5. The one-minute van den Berg reaction is called a direct reaction, and the bilirubin reaction is called direct bilirubin or conjugated bilirubin.
6. While the bilirubin reacting in 30 minutes (with the help of alcohol)  is called indirect or unconjugated bilirubin.

Mechanism of Hyperbilirubinemia:

1. Destruction of the RBCs like hemolytic jaundice.
2. Diseases affecting the metabolism and excretion of bilirubin in the liver.
3. Obstructions like gallstones or pancreatic tumors and certain drugs like:
   1. Chlorpromazine and phenothiazine derivatives.
   2. Estrogen hormones.
   3. Halothane anesthetic drugs.
4. It is raised in the hepatic and post-hepatic types of jaundice.

Normal Values of Conjugated (Direct) Bilirubin

1. Total bilirubin  = 0.3 to 1.0 mg/dL  (5.1 to 17.0 mmol/L)
2. Direct bilirubin   =  0.1 to 0.3 mg/dL  (1.0 to 5.1 mmol/L)
3. Indirect bilirubin (total bilirubin minus direct bilirubin level) = 0.2–0.7 mg/dL

Another source, Total bilirubin level

Raised level of direct bilirubin is seen in the following:

1. Gallstones.
2. Gallbladder tumors.
3. Inflammatory scarring or obstruction of extrahepatic ducts.
4. Extensive liver metastasis.
5. Dubin-Johnson syndrome.
6. Rotor syndrome.
7. Drugs may cause cholestasis.

Raised direct and indirect bilirubin is seen in:

1. Hepatocellular disease.
2. Hepatitis (viral disease).
3. Cirrhosis.
4. Dubon-Johnson syndrome.

Conjugated bilirubin (Direct) <20%:

1. Hemolytic diseases.
2. Gilbert syndrome.
3. Criggler-Najjar syndrome.

Conjugated bilirubin (Direct) 20% to 40%:

1. Suggestive of hepatocellular injury (disease).
2. Bilirubin metabolism abnormalities like:
   1. Dubon-Johnson syndrome.
   2. Rotor’s syndrome.
3. It excludes extrahepatic obstruction.

Conjugated bilirubin (Direct) 40% to 60%:

1. Hepatocellular injury.
2. Extrahepatic obstruction.

Conjugated bilirubin (Direct) >50%:

1. It is seen in extrahepatic obstruction.
2. It excludes hepatocellular injury.

Bilirubin differential diagnosis:

The panic value that needs action are:

• Total bilirubin infants >15 mg/dL will require phototherapy.
• Total bilirubin in infants >20 mg/dL requires a blood transfusion.
• Untreated infants will get kernicterus which may lead to permanent brain damage.

Questions and answers:

Please see more details on bilirubin Total part 1.