Bilirubin

A bilirubin test is used to detect an increased level in the blood. It may be used to help determine the cause of jaundice and/or help diagnose conditions such as liver disease, hemolytic anemia, and blockage of the bile ducts.

Bilirubin is an orange-yellow pigment, a waste product primarily produced by the normal breakdown of heme. Heme is a component of hemoglobin, which is found in red blood cells (RBCs). Bilirubin is ultimately processed by the liver to allow its elimination from the body. Any condition that accelerates the breakdown of RBCs or affects the processing and elimination of bilirubin may cause an elevated blood level.

Two forms of bilirubin can be measured or estimated by laboratory tests:

• Unconjugated bilirubin—when heme is released from hemoglobin, it is converted to unconjugated bilirubin. It is carried by proteins to the liver. Small amounts may be present in the blood.
• Conjugated bilirubin—formed in the liver when sugars are attached (conjugated) to bilirubin. It enters the bile and passes from the liver to the small intestines and is eventually eliminated in the stool. Normally, no conjugated bilirubin is present in the blood.

Usually, a chemical test is used to first measure the total bilirubin level (unconjugated plus conjugated bilirubin). If the total bilirubin level is increased, the laboratory can use a second chemical test to detect water-soluble forms of bilirubin, called "direct" bilirubin. The direct bilirubin test provides an estimate of the amount of conjugated bilirubin present. Subtracting direct bilirubin level from the total bilirubin level helps estimate the "indirect" level of unconjugated bilirubin. The pattern of bilirubin test results can give the healthcare provider information regarding the condition that may be present.

In adults and older children, bilirubin is measured to:

• Diagnose and/or monitor diseases of the liver and bile duct (e.g., cirrhosis, hepatitis, or gallstones)
• Evaluate people with sickle cell disease or other causes of hemolytic anemia; these people may have episodes called crises when excessive RBC destruction increases bilirubin levels.

In newborns with jaundice, bilirubin is used to distinguish the causes of jaundice.

• In both physiologic jaundice of the newborn and hemolytic disease of the newborn, only unconjugated (indirect) bilirubin is increased.
• In much less common cases, damage to the newborn's liver from neonatal hepatitis and biliary atresia will increase conjugated (direct) bilirubin concentrations as well, often providing the first evidence that one of these less common conditions is present.

It is important that an elevated level of bilirubin in a newborn be identified and quickly treated because excessive unconjugated bilirubin damages developing brain cells. The consequences of this damage include mental retardation, learning and developmental disabilities, hearing loss, eye movement problems, and death.

A health practitioner usually orders a bilirubin test in conjunction with other laboratory tests (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase) when someone shows signs of abnormal liver function. A bilirubin level may be ordered when a person:

• Shows evidence of jaundice
• Has a history of drinking excessive amounts of alcohol
• Has suspected drug toxicity
• Has been exposed to hepatitis-causing viruses

Other symptoms that may be present include:

• Dark, amber-colored urine
• Nausea/vomiting
• Abdominal pain and/or swelling
• Fatigue and general malaise that often accompany chronic liver disease

Measuring and monitoring bilirubin in newborns with jaundice is considered standard medical care.

Tests for bilirubin may also be ordered when someone is suspected of having (or known to have) hemolytic anemia as a cause of anemia. In this case, it is often ordered along with other tests used to evaluate hemolysis, such as complete blood count, reticulocyte count, haptoglobin, and LDH.

Adults and children

Increased total bilirubin that is mainly unconjugated (indirect) bilirubin may be a result of:

• Hemolytic or pernicious anemia
• Transfusion reaction
• Cirrhosis
• A relatively common inherited condition called Gilbert syndrome, due to low levels of the enzyme that produces conjugated bilirubin

If conjugated (direct) bilirubin is elevated more than unconjugated (indirect) bilirubin, there typically is a problem associated with decreased elimination of bilirubin by the liver cells. Some conditions that may cause this include:

• Viral hepatitis
• Drug reactions
• Alcoholic liver disease

Conjugated (direct) bilirubin is also elevated more than unconjugated (indirect) bilirubin when there is blockage of the bile ducts. This may occur, for example, with:

• Gallstones present in the bile ducts
• Tumors
• Scarring of the bile ducts

Rare inherited disorders that cause abnormal bilirubin metabolism such as Rotor, Dubin-Johnson, and Crigler-Najjar syndromes, may also cause increased levels of bilirubin.

Low levels of bilirubin are generally not concerning and are not monitored.

Newborns

An elevated bilirubin level in a newborn may be temporary and resolve itself within a few days to two weeks. However, if the bilirubin level is above a critical threshold or increases rapidly, an investigation of the cause is needed so appropriate treatment can be initiated. Increased bilirubin concentrations may result from the accelerated breakdown of red blood cells due to:

• Blood type incompatibility between the mother and her newborn
• Certain congenital infections
• Lack of oxygen (hypoxia) 
• Diseases that can affect the liver

In most of these conditions, only unconjugated (indirect) bilirubin is increased. An elevated conjugated (direct) bilirubin is seen in the rare conditions of biliary atresia and neonatal hepatitis. Biliary atresia requires surgical intervention to prevent liver damage.

Though unconjugated bilirubin may be toxic to brain development in newborns (up to 2-4 weeks of age), it does not pose the same threat to older children and adults. In older children and adults, the "blood-brain barrier" is more developed and prevents bilirubin from gaining access to brain cells. Nevertheless, elevated bilirubin strongly suggests that a medical condition is present that must be evaluated and treated.

Bilirubin is not normally present in the urine. However, conjugated bilirubin is water-soluble and may be eliminated from the body through the urine if it cannot pass into the bile. Measurable bilirubin in the urine usually indicates blockage of liver or bile ducts, hepatitis, or some other form of liver damage and may be detectable early in disease; for this reason, bilirubin testing is integrated into common dipstick testing used for routine urinalysis.

Bilirubin concentrations tend to be slightly higher in males than females. African Americans routinely show lower bilirubin concentrations than non-African Americans. Strenuous exercise may increase bilirubin levels.

Drugs that can decrease total bilirubin include barbiturates, caffeine, penicillin, and high doses of salicylates. The drug atazanavir increases unconjugated (indirect) bilirubin.

Several inherited chronic conditions increase bilirubin levels in the blood and include Gilbert syndrome, Dubin-Johnson syndrome, Rotor syndrome, and Crigler-Najjar syndrome. The first three are usually mild, chronic conditions that can be aggravated under certain conditions but in general cause no significant health problems. For example, Gilbert syndrome is very common; about 1 in every 6 people has this genetic abnormality, but usually people with Gilbert syndrome do not have elevated bilirubin. Crigler-Najjar syndrome is the most serious inherited condition listed; this disorder is relatively rare, and some people with it may die.