Liver Function Tests

Liver Function Tests and Liver Function Overview

Chapter Overview

  • Source: Clinical Biochemistry, 2nd Edition by Nessar Ahmed, Oxford University Press, 2017.

  • Recommended reading for comprehensive revision of liver function tests (LFTs).

Liver Anatomy and Cellular Structure

Components of the Liver

  • Large organ with various cell types:

    • Hepatocytes: Main functional cells.

    • Endothelial cells: Line sinusoids.

    • Ito cells: Store fat and vitamin A.

    • Kupffer cells: Macrophages that filter blood.

    • Pit cells: Natural Killer cells.

Liver Functions

  1. Carbohydrate Metabolism:

    • Glycogen storage and gluconeogenesis to maintain blood glucose levels.

  2. Lipid Metabolism:

    • Synthesis of lipoproteins, cholesterol, and bile.

  3. Protein Metabolism:

    • Produces plasma proteins and urea cycle.

  4. Xenobiotic Metabolism:

    • Detoxification of drugs and toxins.

  5. Hormone Metabolism:

    • Metabolizes steroids and vitamin D.

  6. Vitamin and Glycogen Storage.

  7. Bilirubin Metabolism:

    • Conversion and excretion of bilirubin in bile.

Microvasculature and Blood Flow

Anatomy of Liver Lobule

  • Sinusoids: Fenestrated capillaries allowing exchange with blood.

  • Periportal and Perivenous Zones: Different metabolic functions within the liver lobule.

    • Centripetal flow: Blood flows from portal vein and hepatic artery towards central vein.

Bile Production and Function

  • Bile: Composed of cholesterol, bile acids (taurocholate, glycocholate).

  • Key for lipid digestion.

  • Differences in lipid metabolism between fed and fasted states (e.g., keto-acids produced during starvation).

Urea Synthesis and Protein Turnover

  • Major role in protein metabolism and urea cycle, particularly significant during starvation.

Hepatic Metabolism of Xenobiotics

  • Metabolized by cytochrome P450 enzymes.

  • Converts xenobiotics into water-soluble forms for urinary excretion.

  • Conjugation with polar groups (e.g., glucuronic acid).

Bilirubin Metabolism

Degradation of Red Blood Cells (RBCs)

  1. Old RBCs are removed by splenic macrophages.

  2. Bilirubin: Binds to serum albumin for transport to the liver.

  3. Liver conjugates bilirubin for bile excretion.

  4. Jaundice: Results from ineffective bilirubin disposal.

Liver Diseases

Categories of Liver Diseases

  1. Viral:

    • Includes Hepatitis A-E, Epstein-Barr, Cytomegalovirus.

  2. Metabolic:

    • Examples: Hemochromatosis, biliary tract obstruction.

  3. Vascular:

  4. Parasitic:

    • Schistosomes, liver flukes, etc.

  5. Toxic/Drug Induced:

    • Includes alcohol, other drugs.

  6. Neoplastic:

    • Primary and secondary tumors.

  7. Congenital:

    • Example: Polycystic liver disease.

Cirrhosis

  • Distinct scarring due to repetitive liver insults (e.g., viral infection, drugs).

  • Regeneration possible, but could lead to loss of function and progression to liver failure.

Liver Function Tests (LFTs)

  • LFTs reflect liver function and damage.

Common Tests

  1. Serum aminotransferases (AST, ALT): Indicators of parenchymal damage.

  2. Serum Bilirubin: Indicates cholestasis.

  3. Alkaline Phosphatase and Gamma-Glutamyl Transferase (GGT): Biliary obstruction markers.

  4. Serum Albumin: Indicates synthetic capacity of the liver.

  5. Prothrombin Time (INR): Assesses clotting function.

Aminotransferases Insights

  • ALT/AST ratio: Important for assessing liver damage types.

  • Increased ALT/AST may indicate liver disease (infection, autoimmune conditions, toxins).

  • Rhabdomyolysis may elevate AST/ALT but can be differentiated with specific markers.

Paracetamol Damage

  • Acute poisoning can cause acute liver failure, high AST/ALT.

  • N-acetylcysteine can mitigate damage by replenishing glutathione.

  • Urgent transplant may be necessary in severe cases.

Alkaline Phosphatase Overview

  • Raised levels indicate liver bile obstruction or liver damage.

Gamma-Glutamyl Transferase (GGT)

  • Primary marker for alcohol-induced liver damage.

  • Levels elevated for weeks post-intoxication.

Plasma Proteins Produced by the Liver

  • Albumin: Key osmotic pressure regulator, plays roles in circulation.

  • Also synthesizes metal and vitamin transport proteins (e.g., for vitamin D).

Conclusion

Limitations of LFTs

  • LFTs reflect cellular damage but have limited prognostic value.

  • Requires complementary tests for accurate diagnosis.

  • Emerging imaging technologies offer advanced diagnostic capabilities.

This in-depth note serves as a revision guide for understanding liver functions, structure, diseases, and laboratory evaluations.