Bilirubin:- Part 2 – Conjugated (Direct) Bilirubin, and Conjugated Hyperbilirubinemia
Conjugated (Direct) Bilirubin
Sample for Conjugated (Direct) Bilirubin
- This test is done in the serum of the patient.
- A random sample can be taken.
- This is ideal if the patient has nothing except water 4 to 8 hours before the sample.
- The sample is stable at 4 °C for 3 days.
- Protect the sample from the light because bilirubin is photo-oxidized (photosensitive).
Precautions for Conjugated (Direct) Bilirubin
- Avoid hemolysis and lipemic serum, which will give a false result.
- Avoid drugs that will increase the total bilirubin level like:
- Anabolic steroids.
- Antimalarial drugs.
- Antihypertensive drug-like methyldopa.
- Oral contraceptives.
- Antituberculous drugs like rifampin.
- Medications that will decrease the bilirubin level are:
- Exposure of the sample to sunlight or ultraviolet light may decrease the level.
Pathophysiology of Conjugated (Direct) Bilirubin
- Conjugated hyperbilirubinemia is usually due to hepatocellular injury or cholestasis, intrahepatic or extrahepatic.
- Early diagnosis and management are carried out to prevent complications.
- Bilirubin is yellow to a green pigment of bile derived from the porphyrin structure of hemoglobin.
- Excessive bilirubin within cells and the tissue causes skin jaundice (Icterus) or yellowness.
- Bilirubin estimation is one of the liver function tests.
- Clinically jaundice appears when the bilirubin level exceeds 2 mg/dl.
- Direct bilirubin dissolves in water (water-soluble) and is synthesized in the liver from indirect bilirubin.
- The one-minute van den Berg reaction is called a direct reaction, and the bilirubin reaction is called direct bilirubin or conjugated bilirubin.
- While the bilirubin reacting in 30 minutes (with the help of alcohol) is called indirect or unconjugated bilirubin.
Mechanism of Hyperbilirubinemia:
- Destruction of the RBCs like hemolytic jaundice.
- Diseases affecting the metabolism and excretion of bilirubin in the liver.
- Obstructions like gallstones or pancreatic tumors and certain drugs like:
- Chlorpromazine and phenothiazine derivatives.
- Estrogen hormones.
- Halothane anesthetic drugs.
- It is raised in the hepatic and post-hepatic types of jaundice.
Normal Values of Conjugated (Direct) Bilirubin
- Total bilirubin = 0.3 to 1.0 mg/dL (5.1 to 17.0 mmol/L)
- Direct bilirubin = 0.1 to 0.3 mg/dL (1.0 to 5.1 mmol/L)
- Indirect bilirubin (total bilirubin minus direct bilirubin level) = 0.2–0.7 mg/dL
Another source, Total bilirubin level
|Age||Premature mg/dL||Full-term mg/dL||Adult mg/dL|
|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|
Raised level of direct bilirubin is seen in the following:
- Gallbladder tumors.
- Inflammatory scarring or obstruction of extrahepatic ducts.
- Extensive liver metastasis.
- Dubin-Johnson syndrome.
- Rotor syndrome.
- Drugs may cause cholestasis.
Raised direct and indirect bilirubin is seen in:
- Hepatocellular disease.
- Hepatitis (viral disease).
- Dubon-Johnson syndrome.
Conjugated bilirubin (Direct) <20%:
- Hemolytic diseases.
- Gilbert syndrome.
- Criggler-Najjar syndrome.
Conjugated bilirubin (Direct) 20% to 40%:
- Suggestive of hepatocellular injury (disease).
- Bilirubin metabolism abnormalities like:
- Dubon-Johnson syndrome.
- Rotor’s syndrome.
- It excludes extrahepatic obstruction.
Conjugated bilirubin (Direct) 40% to 60%:
- Hepatocellular injury.
- Extrahepatic obstruction.
Conjugated bilirubin (Direct) >50%:
- It is seen in extrahepatic obstruction.
- 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:
Question 1: At what bilirubin level phototherapy is needed?
When in the infant bilirubin level goes up >15 mg/dL.
Question 2: What is the basic defect in Gilbert's syndrome and Crigler-Najjar syndrome?
The basic defect in Gilbert's syndrome and Crigler-Najjar syndrome, is a deficiency of Glucuronyl transferase enzyme deficiency.
Please see more details on bilirubin Total part 1.