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 produces bile, which contains bile acids (cholesterol metabolites) and bilirubin.
• Bilirubin is the main pigment in bile.
• Approximately 85% of daily bilirubin comes from haemoglobin breakdown, while the remaining comes from red blood cell precursors and other haem-containing proteins (myoglobin, cytochromes, catalase).
• Aged red blood cells are phagocytised by the reticuloendothelial system to release bilirubin.

Bilirubin Metabolism

• Bilirubin is transported in the blood bound to albumin.
• The liver takes bilirubin into the cells via cell membrane-receptor carriers.
• Inside the liver cells, bilirubin is conjugated with glucuronic acid via the action of uridine diphosphate glucuronyl transferase.
• Conjugated bilirubin is water-soluble and excreted into bile via the bile duct.
• In the small intestine, bilirubin is converted to urobilinogen by intestinal bacteria.
• Most urobilinogen is converted to stercobilin and excreted in the faeces.
• A small amount of urobilinogen is reabsorbed into the bloodstream, transported to the liver, and then excreted into the urine.

Bilirubin Levels and Jaundice

• Normal serum bilirubin levels are in the range of 0.2-1.0 mg/dL (3-17 μmol/L).
• A small proportion, approximately 20% (0.2 mg/dL), is in the conjugated form.
• Clinically significant jaundice occurs when plasma bilirubin levels exceed 50 μmol/L.
• Jaundice is characterized by the yellowish pigmentation of the sclera (whites of the eyes) and skin, due to increased bilirubin concentrations in the blood.
• Jaundice occurs when the rate of bilirubin production exceeds the liver's capacity to process and excrete it.

Causes of Increased Bilirubin in Blood

• Haemolysis/Ineffective erythropoiesis: Increased haemoglobin breakdown products, resulting in high bilirubin levels.
• Hepatic causes: Problems with the liver's ability to conjugate bilirubin, such as defective conjugation systems or insufficient uptake.
• Obstruction of the biliary system: Obstructions prevent conjugated bilirubin from entering the small intestine, causing bilirubin to accumulate in the blood.

Types of Jaundice and Diagnostic Tests

• Pre-hepatic jaundice (haemolytic)
• Hepatic jaundice (hepatocellular damage)
• Post-hepatic jaundice (obstructive)
• Tests for jaundice include urinary urobilinogen and bilirubin levels, as well as stool colour examination, to pinpoint the cause of jaundice.

Familial Causes of Raised Bilirubin

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

Reference Ranges

• Adult: Total bilirubin 0.2-1.0 mg/dL (3-17 µmol/L), Unconjugated 0.2-0.8 mg/dL (3-14 µmol/L), Conjugated 0-0.2 mg/dL (0-3 µmol/L).
• Infant total bilirubin levels vary based on prematurity/full-term and age.

Interpretation of Raised Bilirubin Levels

• Raised bilirubin levels alongside elevated liver enzymes indicate possible liver disease or biliary obstruction.
• Raised bilirubin with normal liver enzymes may indicate causes such as haemolysis, Gilbert's syndrome, Crigler-Najjar syndrome, or chronic liver disease.