Bilirubin is formed by the breakdown of red blood cells in the body. The liver helps to excrete it. High levels of bilirubin can lead to jaundice.
This disorder is easily recognizable due to a yellowing of the skin and eyes.
High bilirubin levels can occur in adults, but the disorder is more common in newborn infants. This is because it takes some time after birth for an infant to start efficiently metabolizing bilirubin and excreting it in their stool.
The approximate normal range of bilirubin in the blood serum is:
- 1.2 milligrams per deciliter (mg/dL) for adults
- 1 mg/dL for children under 18 years of age
The skin normally becomes yellow once levels reach between 2 and 3 mg/dL.
Any person who experiences yellowing of the skin or eyes should see their doctor. It may be a sign of a serious condition.
A high level of bilirubin in the blood is known as hyperbilirubinemia.
High bilirubin levels can cause jaundice. Jaundice makes the skin and the whites of the eyes appear yellow, due to the brown and yellow bilirubin in the blood.
There are several reasons for a rise in bilirubin levels outside the newborn period.
These causes can occur before, during, or after the production of bilirubin.
What is bilirubin?
The breakdown of red blood cells (RBCs) in the body produces bilirubin. The bilirubin travels to the liver and is stored in the bile duct. The body ultimately expels bilirubin in stools.
Bilirubin is brown and yellow in color, and it is this pigment that makes feces brown.
The RBCs have a lifespan of around 120 days and renew continually. RBCs contain hemoglobin, which helps transport oxygen around the body, and it is this that gets broken down into bilirubin and other substances. The bilirubin is carried to the liver by albumin, a simple protein.
Once in the liver, bilirubin becomes "conjugated." This means it is water-soluble and can be excreted.
Unconjugated bilirubin is toxic, but conjugated bilirubin is usually not, because it can be removed from the body, as long as nothing is interfering with its removal.
Before reaching the liver
Some conditions cause bilirubin levels to be high before it reaches the liver.
This is the pre-hepatic or "pre-liver" phase, and it can be caused by hemolytic anemia and the reabsorption of internal pools of blood by the body. Hemolytic anemia occurs when too many red blood cells are broken down before the end of their natural life cycle.
In the liver
If the liver is not working properly, it may be unable to make bilirubin water-soluble. This may result in too much bilirubin building up in the liver.
- viruses, such as hepatitis A
- alcoholic liver disease
- some medicine overdoses, including acetaminophen
- autoimmunity, where a disorder of the immune system causes it to attack the cells of the body rather than those that cause disease
After leaving the liver
Once the bilirubin has left the liver, levels may be high because the bilirubin is unable to leave the body.
This may be a result of blockage in one of the other organs that assist excretion, such as gallstones in the gallbladder. This is called the post-hepatic phase.
Other causes include:
Blood tests can measure bilirubin levels. While there is a urine test for bilirubin, it is less accurate and often falsely positive.
If a routine urine test detects bilirubin, a doctor will look at blood serum tests to confirm the results and identify any damage to the liver.
Other tests include:
- further blood tests to assess liver function and test for hepatitis, if indicated
- a physical exam, where a doctor may feel the abdominal area to see if the liver is enlarged or tender.
- imaging tests to visualize the liver. These might include ultrasound, computerized X-ray with a CT scan, or high-powered images with an MRI scan.
- an endoscopy is sometimes carried out to look at the ducts in which the bile travels to the gut.
- a liver biopsy is sometimes needed, although this is uncommon. In this procedure, a small sample of liver tissue is sent to a lab for evaluation.
Treatment depends on the underlying cause of the high bilirubin. If the cause is known, bilirubin might be removed through treatment or lifestyle changes, such as avoiding alcohol.
Gilbert's syndrome is a mild form of high bilirubin. The levels go up and down because the process of removing it from the body is slowed down.
The fluctuation is rarely enough to cause the skin to yellow, but some people may experience symptoms such as stomach pain or fatigue.
Gilbert's syndrome is often discovered when a blood test is done for some other reason.
There is a gene linked to Gilbert's syndrome that shows family patterns of heredity. This gene codes for an enzyme that enables the liver to convert bilirubin to its conjugated form. The absence of this gene in Gilbert's syndrome means this enzyme does not work.
Newborns with high levels of bilirubin have a condition that doctors call neonatal hyperbilirubinemia, or jaundice in neonates.
The Merck Manual states that almost half of all newborns have visible jaundice in the first week after birth.
In adults, bacteria in the gut break down the conjugated bilirubin to create urobilin, and this is excreted in feces. In neonates, the liver takes several days to start adequately processing bilirubin.
The seriousness and medical significance of elevated bilirubin will depend on the cause. The age of the infant, as well as whether they were born premature, is also a factor. In a healthy infant, born at full term, bilirubin levels tend to cause concern when they exceed around 18 mg/dL.
For premature infants, the earlier the delivery occurs in the gestation period, the lower the threshold at which health professionals consider bilirubin levels to be excessive.
High bilirubin levels can be toxic to nerves and cause brain damage.
Most jaundice in infants is not severe, and the symptoms resolve naturally. Prolonged jaundice is more common in infants who are breast-feeding. This type of jaundice is usually not harmful but needs close monitoring.
The neonatal doctor might recommend seeing a lactation consultant among other treatments if they give a jaundice diagnosis.
Some infants receive phototherapy, where a physician exposes the baby to a special kind of blue-green light. This is a standard treatment, in which the light converts the bilirubin to a different form that the liver and kidneys can remove.