What Is Bilirubin?
Bilirubin is a yellow-orange pigment produced as a natural byproduct of the breakdown of haemoglobin - the oxygen-carrying protein found in red blood cells. Your body continuously recycles old or damaged red blood cells, a process that occurs primarily in the spleen and liver. When haemoglobin is broken down, it first forms biliverdin (a green pigment), which is then rapidly converted to bilirubin.
Bilirubin exists in two main forms in the blood:
- Unconjugated (indirect) bilirubin: This is the initial form, produced in the spleen and transported to the liver bound to albumin. It is not water-soluble and cannot be excreted by the kidneys.
- Conjugated (direct) bilirubin: In the liver, bilirubin is "conjugated" - combined with glucuronic acid to make it water-soluble. This conjugated form is then excreted into bile, passes through the bile ducts into the intestines, and is ultimately eliminated in faeces (giving stool its characteristic brown colour). A small amount is reabsorbed and excreted by the kidneys (giving urine its yellow colour).
A total bilirubin test measures the combined amount of both unconjugated and conjugated bilirubin in your blood. When bilirubin accumulates to elevated levels, regardless of the cause, it deposits in the skin and the whites of the eyes, causing the yellow discolouration known as jaundice (or icterus).
Interestingly, bilirubin is not merely a waste product. Research over the past two decades has revealed that bilirubin is a potent antioxidant. Mildly elevated bilirubin levels (as seen in Gilbert's syndrome) are associated with reduced cardiovascular disease risk, lower cancer rates, and protection against oxidative stress-related conditions.
Why Is Bilirubin Tested?
Bilirubin is a core component of the liver function test (LFT) panel and is tested in numerous clinical situations:
- Investigating jaundice: Jaundice is clinically apparent when total bilirubin exceeds approximately 35–50 µmol/L. Bilirubin testing is the first step in determining whether jaundice is pre-hepatic (increased production), hepatic (liver dysfunction), or post-hepatic (bile duct obstruction).
- Liver disease assessment: Elevated bilirubin is a key indicator of liver dysfunction and is included in scoring systems for liver disease severity, such as the Child-Pugh score and the Model for End-Stage Liver Disease (MELD) score.
- Monitoring bile duct obstruction: Gallstones, tumours (pancreatic or bile duct cancer), and strictures that block bile flow cause conjugated bilirubin to accumulate in the blood.
- Haemolytic anaemia diagnosis: Excessive destruction of red blood cells releases large amounts of haemoglobin, overwhelming the liver's capacity to conjugate bilirubin and causing unconjugated bilirubin to rise.
- Neonatal jaundice: Bilirubin monitoring is essential in newborns, where immature liver function can lead to dangerously high unconjugated bilirubin levels that may cause brain damage (kernicterus) if untreated.
- Diagnosing Gilbert's syndrome: A common, benign genetic condition affecting approximately 5–10% of the UK population, causing intermittent mild jaundice due to reduced bilirubin conjugation.
- Pre-surgical assessment: Bilirubin is checked before surgery to ensure adequate liver function.
Normal Bilirubin Ranges
Bilirubin is measured in micromoles per litre (µmol/L) in the UK:
| Measurement | Normal Range (µmol/L) |
|---|---|
| Total bilirubin (adults) | 3–21 µmol/L |
| Conjugated (direct) bilirubin | 0–5 µmol/L |
| Unconjugated (indirect) bilirubin | 3–16 µmol/L |
| Neonates (day 1) | Up to 100 µmol/L |
| Neonates (day 3–5) | Up to 250 µmol/L (physiological jaundice) |
Jaundice becomes clinically visible when total bilirubin exceeds approximately 35–50 µmol/L, though this varies with skin pigmentation. The sclera (whites of the eyes) typically yellow first, followed by the face, trunk, and limbs.
A total bilirubin between 21 and 35 µmol/L is a grey area - mildly elevated, often due to Gilbert's syndrome, and usually benign. However, if accompanied by abnormalities in other liver markers (ALT, AST, ALP, GGT), further investigation is warranted.
What Do High Bilirubin Levels Mean?
Elevated bilirubin (hyperbilirubinaemia) is classified by the predominant type of bilirubin that is raised, which provides important diagnostic information:
Predominantly unconjugated (indirect) hyperbilirubinaemia
- Gilbert's syndrome: By far the most common cause of mildly elevated bilirubin (typically 21–50 µmol/L, occasionally higher). Caused by a genetic reduction in the UGT1A1 enzyme that conjugates bilirubin. Affects 5–10% of the population, is entirely benign, and is often discovered incidentally on routine blood tests. Bilirubin may fluctuate and tends to rise during fasting, stress, illness, or dehydration.
- Haemolytic anaemias: Autoimmune haemolytic anaemia, sickle cell disease, thalassaemia, G6PD deficiency, hereditary spherocytosis, and other haemolytic conditions cause accelerated red blood cell destruction.
- Ineffective erythropoiesis: Conditions such as megaloblastic anaemia (B12/folate deficiency) where red blood cell precursors are destroyed before reaching maturity.
- Large haematoma reabsorption: A significant bruise or internal bleed can transiently raise unconjugated bilirubin as the body reabsorbs the blood.
- Crigler-Najjar syndrome: A rare genetic condition causing severe unconjugated hyperbilirubinaemia due to complete or near-complete absence of UGT1A1 enzyme.
Predominantly conjugated (direct) hyperbilirubinaemia
- Bile duct obstruction: Gallstones, pancreatic head tumours, cholangiocarcinoma, or bile duct strictures prevent conjugated bilirubin from reaching the intestines, causing it to accumulate in the blood. This is associated with pale stools, dark urine, and itching.
- Hepatocellular disease: Hepatitis (viral, autoimmune, alcoholic), cirrhosis, and drug-induced liver injury impair the liver's ability to excrete conjugated bilirubin into bile.
- Primary biliary cholangitis and primary sclerosing cholangitis: Autoimmune conditions affecting the bile ducts.
- Dubin-Johnson syndrome and Rotor syndrome: Rare, benign genetic conditions causing conjugated hyperbilirubinaemia.
- Sepsis: Severe infection can cause cholestatic liver dysfunction.
Mixed hyperbilirubinaemia
Many liver conditions cause both conjugated and unconjugated bilirubin to rise simultaneously - for example, severe hepatitis, cirrhosis, or conditions with both increased production and impaired excretion.
What Do Low Bilirubin Levels Mean?
Low bilirubin is generally not considered clinically significant and is not routinely investigated. However, some research has suggested associations:
- Reduced antioxidant protection: Since bilirubin acts as an antioxidant, very low levels may theoretically offer less protection against oxidative stress. Some epidemiological studies have linked very low bilirubin with increased cardiovascular risk, though this is an area of ongoing research.
- Medications: Certain drugs (phenobarbitone, for example) induce liver enzymes and can lower bilirubin.
- Normal variation: Many healthy people have bilirubin at the lower end of the reference range.
How to Manage Your Bilirubin Levels
Management depends entirely on the cause of the abnormality:
If you have Gilbert's syndrome
- Reassurance: Gilbert's syndrome is benign and requires no treatment. It does not cause liver disease, does not progress, and may actually be protective against cardiovascular disease and certain cancers.
- Stay hydrated: Dehydration can trigger bilirubin spikes.
- Avoid prolonged fasting: Fasting increases bilirubin in Gilbert's syndrome. Regular meals help maintain stable levels.
- Be aware of drug metabolism: Some medications (notably irinotecan, a chemotherapy drug) are metabolised by UGT1A1 and may require dose adjustment in Gilbert's syndrome patients. Always inform your doctor of your diagnosis.
General liver health
- Limit alcohol: Alcohol is a major cause of liver disease and elevated bilirubin.
- Maintain a healthy weight: Obesity increases the risk of NAFLD and gallstones.
- Exercise regularly: Physical activity supports liver health and healthy bile flow.
- Eat a balanced diet: Rich in fruits, vegetables, whole grains, and lean protein.
- Avoid hepatotoxins: Use paracetamol only at recommended doses, avoid recreational drugs, and be cautious with herbal supplements.
If bile duct obstruction is suspected
- Urgent investigation: Obstructive jaundice (conjugated hyperbilirubinaemia with pale stools and dark urine) requires urgent imaging (ultrasound, CT, or MRCP) to identify and relieve the obstruction.
When Should You Get Tested?
Consider having your bilirubin levels checked if you:
- Notice yellowing of the skin or eyes
- Have dark urine or pale stools
- Experience unexplained itching (pruritus)
- Have fatigue, nausea, or abdominal pain
- Consume alcohol regularly
- Take medications that may affect the liver
- Have a family history of liver or blood disorders
- Have previously been told you have Gilbert's syndrome and want to confirm
- Want a comprehensive health screen
Bilirubin is included in standard liver function panels and is part of routine health screening.
Which Lola Health Tests Include Bilirubin?
Bilirubin is included in all Lola Health panels that assess liver function:
- Peak Insights (70 Biomarkers) - Comprehensive panel with full liver function and metabolic markers.
- Vital Check (56 Biomarkers) - Broad health screen including liver enzymes and bilirubin.
- Core Health (45 Biomarkers) - Essential health markers including a complete liver panel.
- Liver Health Blood Test — Focused panel for liver assessment.
All Lola Health tests use a venous blood draw at one of our nationwide partner clinics. Results are reviewed by a doctor and returned within 4 working days.
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