27-29 Bilirubin

Bilirubin: total, direct and indirect; jaundice, Gilbert syndrome, haemolysis, liver disease and bile duct obstruction.

Bilirubin is a yellow pigment formed when old red blood cells are broken down. In the blood it first circulates as unconjugated (indirect) bilirubin, bound to albumin. The liver takes it up and makes it water-soluble by conjugation, producing conjugated (direct) bilirubin, which is excreted in bile. In the gut bacteria convert it to urobilinogen, which colours the stool brown. When bilirubin accumulates, the skin and eyes turn yellow: jaundice, usually visible above about 40–50 µmol/L.

Liver function testsJaundiceGilbert syndrome

Total bilirubin≈ 3–21 µmol/L (0.2–1.2 mg/dL)

Direct (conjugated)< 5 µmol/L (< 0.3 mg/dL)

Indirecttotal − direct

Conversionmg/dL × 17.1 = µmol/L

Figure 1. The bilirubin pathway and where the main causes of raised bilirubin act.

Raised unconjugated (indirect) bilirubin

Gilbert syndrome — a common, harmless inherited reduction of bilirubin conjugation. Bilirubin rises mildly with fasting, illness or stress, while the other liver tests are normal.
Haemolysis — increased red cell breakdown (haemolytic anaemias, transfusion reactions, large bruises), often with anaemia and raised LDH
Newborn jaundice; some medicines

Raised conjugated (direct) bilirubin

Liver diseases: viral, alcoholic or autoimmune hepatitis, cirrhosis, drug-induced liver injury
Bile duct obstruction: gallstones, tumours of the pancreas or bile ducts, strictures, primary biliary or sclerosing cholangitis
Signs: dark urine, pale stools, itching

Seek urgent care

if jaundice appears together with fever and chills, severe abdominal pain, confusion, drowsiness or bleeding, or if a baby develops jaundice in the first day of life or it is worsening.

Planned evaluation

Any new jaundice or unexplained raised bilirubin should be assessed, with direct and indirect fractions, liver enzymes, a blood count and an ultrasound. Isolated mildly raised indirect bilirubin with normal other tests usually means Gilbert syndrome and needs no treatment.

References

Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18–35. doi:10.1038/ajg.2016.517
MedlinePlus. Bilirubin blood test. U.S. National Library of Medicine. medlineplus.gov/ency/article/003479.htm

This article is for general information and does not replace a consultation with a doctor. Laboratory results must be interpreted by a physician together with symptoms and other tests.

Published on 30 April 2024