Type of test Blood

Normal findings Adult/elderly/child:

Total bilirubin: 0.3-1.0 mg/dL or 5.1-17 μmol/L (SI units)
 Indirect bilirubin: 0.2-0.8 mg/dL or 3.4-12.0 μmol/L (SI units)
Direct bilirubin: 0.1-0.3 mg/dL or 1.7-5.1 μmol/L (SI units)

Newborn:
 Total bilirubin: 1.0-12.0 mg/dL or 17.1-205 μmol/L (SI units)

Possible critical values

Total bilirubin Adult: > 12 mg/dL , Newborn: > 15 mg/dL

Test explanation and related physiology

 Bile, which is formed in the liver, has many constituents, including bile salts, phospholipids, cholesterol, bicarbonate, water, and bilirubin. Bilirubin metabolism begins with the breakdown of red blood cells (RBCs) in the reticuloendothelial system (Figure 1). Hemoglobin is released from RBCs and broken down to heme and globin molecules. Heme is then catabolized to form biliverdin, which is transformed into bilirubin. This form of bilirubin is called unconjugated (indirect) bilirubin. In the liver, indirect bilirubin is conjugated with a glucuronide, resulting in conjugated (direct) bilirubin. The conjugated bilirubin is then excreted from the liver cells and into the bile ducts and then into the bowel.

Fig1. Bilirubin metabolism and excretion. The spleen, liver, kidneys, and gastrointestinal tract contribute to this process.

Jaundice is the discoloration of body tissues caused by abnormally high blood levels of bilirubin. This yellow discoloration is recognized when the total serum bilirubin exceeds 2.5 mg/dL.

Physiologic jaundice of the newborn occurs if the newborn’s liver is immature and does not have enough conjugating enzymes.

When the jaundice is recognized either clinically or chemically, it is important (for therapy) to differentiate whether it is predominantly caused by unconjugated or conjugated bilirubin. This in turn will help differentiate the etiology of the defect. In general, jaundice caused by hepatocellular dysfunction (e.g., hepatitis) results in elevated levels of unconjugated bilirubin.

Jaundice resulting from extrahepatic obstruction of the bile ducts (e.g., gallstones or tumor blocking the bile ducts) results in elevated conjugated bilirubin levels; this type of jaundice usually can be resolved surgically or endoscopically.

The total serum bilirubin level is the sum of the conjugated (direct) and unconjugated (indirect) bilirubin. These are separated out when fractionation or differentiation of the total bilirubin to its direct and indirect parts is requested from the lab oratory. Normally the unconjugated bilirubin makes up 70% to 85% of the total bilirubin. In patients with jaundice, when more than 50% of the bilirubin is conjugated, it is considered a conjugated hyperbilirubinemia from gallstones, tumors, inflammation, scarring, or obstruction of the extrahepatic ducts. Unconjugated hyperbilirubinemia exists when less than 15% to 20% of the total bilirubin is conjugated. Diseases that typically cause this form of jaundice include accelerated erythrocyte (RBC) hemolysis or hepatitis.

Interfering factors

 • Blood hemolysis and lipemia can produce erroneous results.

* Drugs that may cause increased levels of total bilirubin include allopurinol, anabolic steroids, antibiotics, antimalHelveticas, ascorbic acid, azathioprine, chlorpropamide, cholinergics, codeine, dextran, diuretics, epinephrine, meperidine, methotrexate, methyldopa, monoamine oxidase inhibitors, morphine, nicotinic acid (large doses), oral contraceptives, phenothiazines, quinidine, rifampin, salicylates, steroids, sulfonamides, the ophylline, and vitamin A.

* Drugs that may cause decreased levels of total bilirubin include barbiturates, caffeine, penicillin, and salicylates (large doses).

Procedure and patient care

 • See inside front cover for Routine Blood Testing.

 • Fasting: verify with laboratory

• Blood tube commonly used: red

 • Use a heel puncture for blood collection in infants.

• Prevent hemolysis of blood during phlebotomy.

 • Do not shake the tube; inaccurate test results may occur.

• Protect the blood sample from bright light. Prolonged exposure (> 1 hour) to sunlight or artificial light can reduce bilirubin content.

Abnormal findings

 Increased levels of conjugated (direct) bilirubin

- Gallstones

- Extrahepatic duct obstruction (tumor, inflammation, gallstone, scarring, or surgical trauma)

- Extensive liver metastasis

- Cholestasis from drugs

- Dubin–Johnson syndrome

- Rotor syndrome

Increased levels of unconjugated (indirect) bilirubin

 - Hemolytic disease of the newborn

- Hemolytic jaundice

- Large-volume blood transfusion

- Resolution of a large hematoma

- Hepatitis

- Sepsis

- Neonatal hyperbilirubinemia

- Hemolytic anemia

 - Crigler–Najjar syndrome

- Gilbert syndrome

- Pernicious anemia

 - Cirrhosis

- Transfusion reaction

- Sickle cell anemia