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Bilirubin, Total

SI UNITS (recommended)

CONVENTIONAL UNITS

(TBil – Total Bilirubin – Combined Direct + Indirect Bilirubin)

Synonyms

  • Total bilirubin
  • TBil
  • Serum bilirubin
  • Conjugated + unconjugated bilirubin
  • Direct + indirect bilirubin
  • Total serum bile pigments

Units of Measurement

  • mmol/L
  • µmol/L
  • mg/dL
  • mg/100 mL
  • mg%
  • mg/L
  • µg/mL

Description

Total bilirubin measures the sum of:

  1. Unconjugated (indirect) bilirubin
    • Water-insoluble
    • Bound to albumin
    • Formed from hemoglobin breakdown
  2. Conjugated (direct) bilirubin
    • Water-soluble
    • Formed in liver via UGT1A1 enzyme
    • Excreted into bile

Total bilirubin reflects:

  • Hemolysis
  • Liver conjugation ability
  • Bile excretion

It is one of the most important liver function parameters.

Physiological Production

Daily bilirubin production:

  • 80–85% from senescent RBC breakdown
  • 10–15% from ineffective erythropoiesis
  • <5% from muscle/myoglobin/heme enzymes

Hepatocytes conjugate bilirubin with glucuronic acid → excretion into bile.

Clinical Significance

Elevated Total Bilirubin

1. Pre-hepatic (Hemolytic) Causes

↑ production → unconjugated bilirubin predominant

  • Hemolytic anemias
  • Autoimmune hemolysis
  • G6PD deficiency
  • Sickle cell disease
  • Thalassemia
  • Ineffective erythropoiesis (B12/folate deficiency)

2. Hepatic Causes

Both direct & indirect may rise

  • Viral hepatitis
  • Alcoholic hepatitis
  • NASH / NAFLD
  • Drug-induced liver injury (DILI)
  • Cirrhosis
  • Wilson disease
  • Crigler–Najjar (UGT1A1 deficiency)

3. Post-hepatic (Obstructive) Causes

Direct bilirubin predominant

  • Gallstones
  • Biliary strictures
  • Pancreatic cancer
  • Primary sclerosing cholangitis
  • Primary biliary cholangitis
  • Cholestasis of pregnancy

4. Neonatal Hyperbilirubinemia

  • Physiologic jaundice
  • Breastfeeding jaundice
  • UGT1A1 immaturity
  • Hemolytic disease of newborn (HDN)
  • Biliary atresia → direct bilirubin elevation

Low Total Bilirubin

Not significant clinically.
Rarely seen in:

  • Severe oxidative stress
  • Certain medications
  • Hypoalbuminemia

Reference Intervals

(Tietz 8E + IFCC + AASLD + Mayo/ARUP)

Adults

  • 0.3 – 1.2 mg/dL
  • 5 – 21 µmol/L

Neonates

  • Day 1: < 6 mg/dL
  • Day 2: < 8 mg/dL
  • Day 3–5: < 12 mg/dL
  • 15 mg/dL → concerning

  • Direct bilirubin > 1 mg/dL → always abnormal

Clinically Significant Levels

  • > 2–3 mg/dL → visible jaundice
  • > 20–25 mg/dL (neonates) → risk of kernicterus
  • > 30 mg/dL (adults) → severe hepatobiliary disease

Unit Meanings

UnitExplanation
mmol/Lmillimole per liter
µmol/Lmicromole per liter
mg/dLmilligram per deciliter
mg%mg per 100 mL
mg/100 mLidentical to mg%
mg/Lmilligram per liter
µg/mLmicrogram per milliliter

Diagnostic Uses

1. Jaundice Evaluation

Differentiate:

  • Hemolysis (indirect)
  • Hepatocellular disease (mixed)
  • Obstruction (direct)

2. Liver Function Assessment

Part of:

  • LFT panel
  • Cirrhosis monitoring
  • Viral hepatitis management
  • Drug hepatotoxicity evaluation

3. Neonatal Hyperbilirubinemia

Essential for:

  • Phototherapy decisions
  • Exchange transfusion threshold
  • Early detection of biliary atresia (direct bilirubin)

4. Hemolysis Workup

Indirect bilirubin rises before anemia develops.

Analytical Notes

  • Light-sensitive → protect sample from light.
  • Lipemia may slightly increase results.
  • Hemolysis does not affect bilirubin significantly.
  • Use serum or heparinized plasma.
  • Methods: Jendrassik–Grof diazo reaction (gold standard).

Clinical Pearls

  • Direct vs indirect bilirubin pattern is key to diagnosis.
  • Isolated unconjugated elevation → hemolysis, Gilbert syndrome.
  • Predominant direct bilirubin elevation → cholestasis/obstruction.
  • Very high bilirubin with AST/ALT <200 → consider sepsis-related cholestasis.
  • Kernicterus risk increases dramatically when unconjugated bilirubin >20 mg/dL in neonates.

Interesting Fact

Because bilirubin is an antioxidant, very mild elevation (e.g., Gilbert syndrome) may be protective against cardiovascular disease.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Bilirubin & Liver Function.
  2. IFCC Bilirubin Standardization.
  3. AASLD Guidelines - Jaundice & Cholestatic Disease.
  4. Mayo Clinic Laboratories - Total Bilirubin.
  5. ARUP Consult - Hyperbilirubinemia Diagnosis.
  6. MedlinePlus / NIH - Bilirubin Testing.
  7. Neonatal Jaundice Guidelines - AAP & Pediatric Hepatology Texts.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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