What is bilirubin?
When red blood cells reach the end of their 120-day lifespan, they are broken down in the spleen. The haemoglobin releases a yellow pigment called bilirubin. This travels to the liver, gets processed (conjugated), and is excreted in bile into the gut, giving stools their brown colour and contributing to the yellow colour of urine. When this pathway is disrupted at any point, bilirubin builds up in the blood, causing jaundice.
Types of bilirubin in your report
| Test | Normal Range (mg/dL) | What it measures |
|---|---|---|
| Total Bilirubin | 0.2 – 1.2 | All bilirubin combined |
| Direct (Conjugated) | 0.0 – 0.3 | Processed by liver: bile duct problem if high |
| Indirect (Unconjugated) | 0.2 – 0.9 | Pre-liver: haemolysis or Gilbert's if high |
What does HIGH total bilirubin mean?
HIGH Total bilirubin above 1.2 mg/dL
Jaundice (yellow skin/eyes) becomes visible when total bilirubin exceeds 2.5–3 mg/dL. Causes depend on WHICH type is elevated:
High INDIRECT bilirubin: pre-liver causes
High indirect bilirubin
Gilbert's Syndrome (most common: affects 5–10% of people, harmless): mildly elevated indirect bilirubin that fluctuates with fasting, stress or illness. No treatment needed. Haemolytic anaemia: red blood cells being destroyed faster than the liver can process bilirubin. Causes: sickle cell disease, thalassaemia, G6PD deficiency, autoimmune haemolysis. Neonatal jaundice: very common in newborns, immature liver can't process bilirubin fast enough.
High DIRECT bilirubin: liver/bile duct causes
High direct bilirubin
High direct (conjugated) bilirubin means the liver has processed it but can't excrete it: a bile duct blockage or liver cell damage. Causes: gallstones blocking the bile duct (most common surgical cause), viral hepatitis (A, B, E), alcoholic hepatitis, cholestasis of pregnancy, pancreatic cancer compressing the bile duct (painless jaundice in elderly = investigate urgently), primary biliary cholangitis.
Questions to ask your doctor
- Is my bilirubin rise direct or indirect, and what does that narrow it down to?
- Do I need a liver ultrasound to check for gallstones or bile duct dilation?
- Could this be Gilbert's syndrome, a harmless condition?
- Should I test for Hepatitis A, B and E?
Frequently asked questions
Should a borderline Bilirubin result be repeated?
Do Bilirubin results from two different laboratories compare directly?
Does Bilirubin need to be measured fasting?
References
The clinical information on this page is drawn from peer-reviewed sources indexed by the US National Library of Medicine. Links go to the source so you can read it yourself.
- Liver Function Tests. In: StatPearls. Treasure Island (FL): StatPearls Publishing. NCBI Bookshelf NBK482489
References
Sources cited on this page. PubMed links open the original abstract.
- Fevery J. Bilirubin in clinical practice: a review. Liver Int. 2008;28(5):592–605. PMID 18785961 · doi:10.1111/j.1478-3231.2008.01716.x
The bilirubin pathway – from haem to bile
Bilirubin is the yellow breakdown product of haem – the iron-containing group at the centre of haemoglobin. When red blood cells reach the end of their 120-day lifespan, the spleen and liver macrophages destroy them. Haemoglobin is released, and haem is converted to bilirubin. This unconjugated bilirubin is fat-soluble (insoluble in water) and is transported to the liver bound to albumin.
In the liver, hepatocytes conjugate bilirubin with glucuronic acid – making it water-soluble (conjugated bilirubin). Conjugated bilirubin is secreted into bile, stored in the gallbladder, and released into the small intestine where bacteria convert it to urobilinogen. Most urobilinogen is excreted in faeces (giving stool its brown colour); a small amount is reabsorbed and excreted in urine (giving urine its yellow colour). When bilirubin accumulates in blood above approximately 35–50 µmol/L, it deposits in skin and sclerae, causing visible jaundice.
Conjugated versus unconjugated bilirubin – diagnosing the level of problem
The total bilirubin test is usually reported alongside its fractionation into direct (conjugated) and indirect (unconjugated) components. This fractionation is essential for diagnosis:
- Predominantly unconjugated bilirubin (direct fraction below 20% of total):
- Haemolysis – accelerated red cell destruction producing more unconjugated bilirubin than the liver can conjugate
- Gilbert's syndrome – the most common cause of mild isolated unconjugated hyperbilirubinaemia (up to 70 µmol/L). A benign genetic variant (UGT1A1 polymorphism) reducing conjugation efficiency. Bilirubin rises with fasting, illness, or exercise. Liver enzymes and haemolysis markers are normal. No treatment required; reassurance is the only intervention.
- Neonatal physiological jaundice – neonates have immature conjugation machinery and elevated haemoglobin turnover
- Predominantly conjugated bilirubin (direct fraction above 50% of total):
- Hepatocellular disease (hepatitis, cirrhosis) – damaged hepatocytes leak conjugated bilirubin back into blood
- Cholestatic disease (biliary obstruction) – conjugated bilirubin cannot flow into the gut; it accumulates in blood. Pale stools (no pigment reaching gut) and dark urine (conjugated bilirubin excreted by kidney, which normally does not occur) are diagnostic features
- Dubin-Johnson and Rotor syndromes – rare benign inherited conditions of conjugated bilirubin transport
Bilirubin monitoring in clinical practice
Serial bilirubin measurement is used to monitor: progress of obstructive jaundice after ERCP or biliary stent placement; response to phototherapy in neonatal jaundice; disease activity in primary biliary cholangitis (rising bilirubin indicates cirrhosis progression – above 17 µmol/L is a component of the GLOBE score for PBC prognosis); and in sepsis-associated cholestasis, where bilirubin is a component of the SOFA (Sequential Organ Failure Assessment) score used in ICU prognostication.
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