Liver Function Tests: Plasma Bilirubin

Liver Function Tests: Plasma Bilirubin

• Bilirubin is a breakdown product of haemoglobin, a component of red blood cells.
• The liver synthesizes bile, containing bile acids (derived from cholesterol) and bilirubin.
• Bilirubin is the principal pigment in bile.
• Approximately 85% of daily bilirubin is formed from the breakdown of haemoglobin.
• The remaining bilirubin comes from erythrocyte precursors and the breakdown of haem-containing proteins (like myoglobin, cytochromes, and catalase).
• Aged red blood cells are phagocytosed by the reticuloendothelial system, releasing haemoglobin, which is broken down into bilirubin.
• Normal serum bilirubin levels range from 0.2-1.0 mg/dL (3-17 µmol/L).
• Only a small proportion (around 0.2 mg/dL, or 1/5th of the total) is in conjugated form.
• The majority of bilirubin (~90%) is excreted in the faeces as urobilinogen, which is converted to stercobilin. A small amount (about ~10%) is filtered by the kidney and excreted in the urine.

Bilirubin Metabolism

• Bilirubin, initially unconjugated, is transported in the blood bound to albumin.
• In the liver, unconjugated bilirubin is taken up by hepatocytes.
• Inside the hepatocytes, the bilirubin is conjugated to glucuronic acid, making it water-soluble.
• Conjugated bilirubin is secreted into the bile canaliculi, then transported to the small intestine.
• In the small intestine, bacteria metabolize conjugated bilirubin to urobilinogen.
• A portion of urobilinogen is reabsorbed into the portal circulation and returned to the liver.
• Most urobilinogen is eliminated in the faeces as stercobilin.

Clinical Significance

• Elevated plasma bilirubin levels (>50 µmol/L) can lead to jaundice.
• Jaundice is characterized by yellowish pigmentation of the sclera (whites of the eyes) and skin.
• Elevated bilirubin levels are caused by an imbalance between bilirubin production and removal.
• Causes of increased bilirubin include haemolysis, ineffective erythropoiesis, liver dysfunction, and biliary obstruction.

Interpretation of Elevated Bilirubin Levels

• Elevated bilirubin levels with elevated liver enzymes suggest liver disease or biliary obstruction.
• Elevated bilirubin with normal liver enzymes may indicate conditions like haemolysis, Gilbert's syndrome, or Crigler-Najjar syndrome.

Bilirubin Summary

• Bilirubin originates from red blood cell breakdown and certain haemoglobin-containing proteins.
• It's primarily transported bound to albumin, most in unconjugated form, unable to pass through filter membranes.
• In the liver, bilirubin is conjugated, becoming water-soluble and able to be excreted via bile duct.
• In the small intestine, it's metabolized by bacteria to urobilinogen, then to stercobilin, mainly excreted in faeces.

Reference Ranges (Adult)

• Total bilirubin: 0.2-1.0 mg/dL (3-17 µmol/L)
• Unconjugated bilirubin: 0.2-0.8 mg/dL (3-14 µmol/L)
• Conjugated bilirubin: 0-0.2 mg/dL (0-3 µmol/L)

Reference Ranges (Infant)

• Reference ranges for total bilirubin are provided in mg/dL (specific ranges vary by age, and if premature or full-term).

Types of Jaundice

• Haemolytic: Pre-hepatic. Caused by increased red blood cell destruction.
• Hepatic: Hepatocellular. Caused by liver dysfunction.
• Obstructive: Post-hepatic. Caused by bile duct blockage.

Familial Causes of Raised Bilirubin

• Gilbert's syndrome: Reduced bilirubin uptake by liver cells.
• Crigler-Najjar syndrome: Impaired bilirubin conjugation.
• Dubin-Johnson syndrome: Defective secretion of conjugated bilirubin.