Bilirubin

When bilirubin concentrations in the blood increase it leads to a condition called jaundice (yellowing of the skin and/​or the whites of the eyes). Further testing is often needed to help doctors find out the cause of the high bilirubin. Too much bilirubin may mean that too many red blood cells are being destroyed or liver damage is present.

It is not uncommon to see high unconjugated bilirubin concentrations in newborn babies from the second to the seventh day of life. This transient condition is called physiological jaundice. Bilirubin concentrations rarely peak higher than five times the upper limit of normal. Up to 50% of full-term newborns and an even greater percentage of pre-term babies may have jaundice. The newborn’s liver is not fully mature and is unable to process bilirubin fast enough. Physiological jaundice is not abnormal and resolves within a few days.

Jaundice in a newborn baby is likely to be abnormal if it occurs within the first 24 hours of life. In this situation the newborn’s red blood cells may be being destroyed because of blood incompatibility between the baby and mother, called haemolytic disease of the newborn. Jaundice in a newborn baby that persists longer than 8 – 14 days is also likely to be abnormal. In this situation the jaundice may be caused by abnormal metabolism in the liver or malformation of the bile ducts.

In adults or older children, bilirubin is measured to diagnose and monitor liver diseases such as cirrhosis, hepatitis, or gallstones. Patients with sickle cell disease or other causes of haemolytic anaemia may have episodes where excessive red blood cell destruction takes place, increasing bilirubin concentrations in the blood.

A doctor usually requests a bilirubin test in conjunction with other laboratory tests (this usually includes ALP and ALT) as a group called liver function tests (LFTs). LFTs may be requested when a patient:

• shows evidence of jaundice
• has a history of drinking excessive amounts of alcohol
• has suspected drug toxicity or is taking medications that are metabolised by the liver or that can affect liver function
• has been exposed to hepatitis viruses
• is ill, to determine if the liver is affected and that, if needed, it is safe to give drugs metabolised by the liver

Other signs and symptoms of liver disease that may prompt testing of LFTs include:

• dark, amber-coloured urine
• pale stools
• itching
• nausea and vomiting
• abdominal pain and/​or swelling
• fatigue and general malaise

Adults and children: Bilirubin concentrations can be used to identify liver disease or to monitor the progression of jaundice. Increased total or unconjugated bilirubin may be a result of haemolytic, sickle cell or pernicious anaemias or a transfusion reaction. If conjugated bilirubin is elevated, there may be some kind of blockage of the liver or bile ducts, hepatitis, trauma to the liver, cirrhosis, a drug reaction, or long-term alcohol abuse.

Newborns: Excessive unconjugated bilirubin damages developing brain cells in infants (kernicterus) and may cause mental retardation, hearing loss, speech difficulties or fits. It is important that bilirubin concentrations in newborns do not get too high. When the concentration of unconjugated bilirubin is greater than 15 times the upper limit of normal, special treatment is used to reduce it and prevent kernicterus: phototherapy (exposure of the skin to blue light)and sometimes exchange blood transfusion.

An excessive unconjugated bilirubin concentration may result from the breakdown of red blood cells due to blood typing incompatibility between the mother and her infant. For example, if the mother is Rhesus negative and the foetus inherits the father’s Rhesus positive trait, foetal red blood cells may cross the placenta into the mother’s blood and she may develop antibodies which cross back into the foetus and cause haemolysis of the foetal Rh-positive red blood cells, resulting in excessively elevated unconjugated bilirubin.

Determining conjugated and unconjugated bilirubin concentrations in newborns with jaundice is standard medical care. Malformation of the bile ducts (biliary atresia) obstructs the flow of bile, damaging the liver and causing raised concentrations of conjugated bilirubin. The condition requires early surgical treatment to avoid the need for liver transplantation.

Although unconjugated bilirubin may be toxic to brain development in newborns (up to the age of about 2–4 weeks), high bilirubin concentrations in older children and adults does not pose the same threat. In older children and adults, the ​‘blood-brain barrier’ is more developed and prevents bilirubin from crossing into the brain. Elevated bilirubin in children or adults, however, strongly suggests an underlying disease that must be investigated and treated.

Bilirubin is not normally present in the urine. However, conjugated bilirubin is water-soluble and therefore may be excreted from the body in the urine when concentrations increase in the blood. Its presence in the urine usually indicates blockage of liver or bile ducts, hepatitis or some other liver damage. The most common method for detecting urine bilirubin is using the dipstick test that is part of urinalysis.

Several inherited conditions including Gilbert’s syndrome, Dubin-Johnson syndrome, Rotor’s syndrome, and Crigler-Najjar syndrome can cause a raised bilirubin concentration. Of these four syndromes the rarest, Crigler-Najjar, is the most serious. The first three are usually mild, long-term conditions that can be aggravated under certain conditions, but in general cause no significant health problems. In particular, Gilbert’s syndrome is relatively common (it may affect up to 5% of the population). Gilbert’s causes a small increase in bilirubin, but no clinical problems other than having to be excluded as a reason for mild jaundice. Prolonged fasting or general illness can cause mild jaundice in subjects with Gilbert’s syndrome.