Chemical Pathology of the Hepatobiliary System

Structure of the Liver

  • Largest internal organ in the human body (weights 1.2 kg).

  • Composed of 2 lobes: right (larger) and left.

  • Highly vascularized with blood supply from:

    • Hepatic artery (25% oxygenated blood).

    • Portal vein (75% deoxygenated blood).

Significance of Portal Circulation

  • Initial absorption of nutrients, toxins, and pathogens from the intestine.

  • Ensures removal of toxins and pathogens from the bloodstream before systemic circulation.

  • Stores excess nutrients, releasing them to prevent hyperglycemia (e.g., glucose as glycogen).

Liver Cell Types

  • Hepatocytes:

    • Make up 80% of functional mass.

    • Responsible for most liver functions and capable of regeneration.

  • Kupffer cells:

    • Specialized macrophages that destroy pathogens and debris.

  • Hepatic stellate cells:

    • Store Vitamin A and produce collagen, contributing to fibrosis in liver damage.

Functions of the Liver

  • Synthetic Functions:

    • Synthesis of enzymes: ASAT, ALT, LDH, alkaline phosphatase, and others.

    • Synthesis of lipoproteins and plasma proteins (e.g., clotting factors).

    • Bile synthesis, which emulsifies fats.

    • Produces various growth factors and hormones.

  • Metabolic Functions:

    • Protein metabolism, glucose handling (glycolysis, gluconeogenesis, glycogen metabolism).

    • Metabolism of fats and cholesterol.

    • Drug metabolism and detoxification.

Bilirubin Metabolism

  • Result of RBC breakdown (75% from hemoglobin).

  • Bilirubin is transported to the liver for conjugation and excretion in bile.

  • Increased Unconjugated Bilirubin (UCB) causes jaundice; different types include:

    • Prehepatic: Excess production (e.g., hemolytic anemias).

    • Hepatic: Impaired conjugation (e.g., Gilbert's syndrome).

    • Posthepatic: Obstruction of bile flow (e.g., gallstones).

Liver Failure

  • Acute Liver Failure: Rapid onset, life-threatening (common causes: viral hepatitis, overdoses, toxins).

  • Chronic Liver Failure: Gradual progression (common causes: chronic hepatitis, alcohol misuse, cirrhosis).

Liver Function Tests

  • Evaluates liver function: enzymes (AST, ALT, alkaline phosphatase, bilirubin levels).

  • Increased AST and ALT indicate hepatocellular injury; ALT is liver-specific.

  • Alkaline phosphatase elevation suggests cholestasis.

Clinical Enzymology

  • Enzymes can indicate various conditions through levels in plasma.

  • Increased activity can result from tissue injury or increased production, whereas decreased activity may signal deficiencies or enzyme inhibition.

  • Isoenzymes: Different forms found in various tissues; used to pinpoint organ damage (e.g., LDH, CK).

  • LDH patterns can indicate myocardial infarction or other diseases.