Bilirubin results from the breakdown of hemoglobin in the RBCs and is a byproduct of hemolysis (i.e., RBC destruction). It is produced by the reticuloendothelial system. Removed from the body by the liver, which excretes it into the bile, bilirubin gives the bile its major pigmentation. Usually, a small amount of bilirubin is found in the serum. A rise in serum bilirubin levels occurs when there is excessive destruction of RBCs or when the liver is unable to excrete the normal amounts of bilirubin produced.

There are two major forms of bilirubin in the body: conjugated bilirubin and unconjugated bilirubin, sometimes termed direct and indirect bilirubin, respectively. Unconjugated bilirubin circulates freely in the blood until it reaches the liver, where it is conjugated with glucuronide transferase and then excreted into the bile. An increase in unconjugated bilirubin is more frequently associated with increased destruction of RBCs (hemolysis) as well as in neonatal jaundice. An increase in free-flowing bilirubin is more likely seen in dysfunction or blockage of the liver. A routine examination measures only the total bilirubin. A normal level of total bilirubin rules out any significant impairment of the excretory function of the liver or excessive hemolysis of red cells. Only when total bilirubin levels are elevated will there be a call for differentiation of the bilirubin levels by conjugated and unconjugated types.

The measurement of bilirubin allows evaluation of liver function and hemolytic anemias. For infants younger than 15 days, a neonatal, or more specifically an unconjugated, bilirubin measurement may be necessary.

Adults:

• Total: 0.3–1.0 mg/dL or 5–17 μmol/L

• Conjugated (direct): 0.0–0.3 mg/dL or 0.0–5.1 μmol/L

• Unconjugated (indirect): 0.2–0.8 mg/dL or 3.4–12 mmol/L

1. Obtain a 5-mL nonhemolyzed sample (red-topped tube) from a fasting patient. Observe standard precautions. Serum is used.

2. Protect the sample from ultraviolet light (sunlight).

3. Avoid air bubbles and unnecessary shaking of the sample during blood collection.

4. If the specimen cannot be examined immediately, store it away from light and in a refrigerator.

1. Total bilirubin elevations accompanied by jaundice may be due to hepatic, obstructive, or hemolytic causes.

   1. Hepatocellular jaundice results from injury or disease of the parenchymal cells of the liver and can be caused by the following conditions:

      1. Viral hepatitis

      2. Cirrhosis

      3. Infectious mononucleosis

      4. Reactions to certain drugs such as chlorpromazine (antipsychotic medication used to treat manic depression or schizophrenia)

   2. Obstructive jaundice is usually the result of obstruction of the common bile or hepatic ducts due to stones or neoplasms. The obstruction produces high conjugated bilirubin levels due to bile regurgitation.

   3. Hemolytic jaundice is due to overproduction of bilirubin resulting from hemolytic processes that produce high levels of unconjugated bilirubin. Hemolytic jaundice can be found in the following conditions:

      1. After blood transfusions, especially those involving many units

      2. Pernicious anemia

      3. Sickle cell anemia

      4. Transfusion reactions (ABO or Rh incompatibility)

      5. Crigler–Najjar syndrome (a severe disease that results from a genetic deficiency of a hepatic enzyme needed for the conjugation of bilirubin)

      6. Erythroblastosis fetalis (see Neonatal Bilirubin, Total and Fractionated [“Baby Bili”])

   4. Miscellaneous diseases:

      1. Dubin–Johnson syndrome (autosomal recessive disorder resulting in an increase in the serum levels of conjugated bilirubin)

      2. Gilbert disease (familial hyperbilirubinemia)

      3. Nelson disease (with acute liver failure)

      4. Pulmonary embolism/infarct

      5. Heart failure

2. Elevated indirect (unconjugated) bilirubin levels occur in the following conditions:

   1. Neonatal jaundice

   2. Hemolytic anemias due to a large hematoma

   3. Trauma in the presence of a large hematoma

   4. Hemorrhagic pulmonary infarcts

   5. Crigler–Najjar syndrome (rare)

   6. Gilbert disease (conjugated hyperbilirubinemia; rare)

3. Elevated direct (conjugated) bilirubin levels occur in the following conditions:

   1. Cancer of the head of the pancreas

   2. Choledocholithiasis

   3. Dubin–Johnson syndrome

Pretest Patient Care

1. Explain test purpose and procedure and relation of results to jaundice.

2. Ensure that the patient is fasting, if possible.

3. Follow guidelines in Chapter 1 for safe, effective, informed pretest care.