Liver Function Tests Review

Liver Function Tests Overview

Key Biochemical Concepts of the Liver (SFB1004)

  • Central Pathways: Includes urea synthesis, deamination/transamination, and gluconeogenesis.

  • Liver Anatomy: Composed of hepatocytes (main cells) and other cells such as endothelial cells, Ito cells (lipid storing), Kupffer cells (macrophages), and pit cells (Natural Killer cells).

Liver Functions

  • Carbohydrate Metabolism: Maintains blood glucose levels via glycogen and gluconeogenesis.

  • Lipid Metabolism: Involves lipoprotein, cholesterol, and bile synthesis.

  • Protein Metabolism: Involves synthesis of plasma proteins, urea cycle, and transamination processes.

  • Xenobiotic Metabolism: Detoxifies foreign substances.

  • Hormone Synthesis: Includes steroids and vitamin D.

  • Storage: Stores vitamins and glycogen.

  • Bilirubin Metabolism: Involves bile synthesis and excretion.

Liver Structure

  • Liver Lobule: Basic functional unit of the liver.

  • Microvascular Structure: Includes sinusoids (fenestrated capillaries) with significant separation of metabolic processes at periportal (oxidative) and perivenous (reductive) ends.

  • Blood Flow: Centripetal flow dictated by blood vessel organization.

Bile Production and Lipid Metabolism

  • Bile Composition: Includes cholesterol, bile salts (taurocholate and glycocholate).

  • States of Metabolism: Different metabolic processes during fed vs fasted states, including keto-acid production during starvation.

  • Urea Synthesis: Major site for protein turnover in the body; changes during starvation.

Xenobiotic Metabolism

  • Enzymatic Action: Cytochrome P450 enzymes convert polar compounds to water-soluble forms for urinary excretion through conjugation with polar groups (e.g., glucuronic acid).

  • Bilirubin Processing: Product of hemoglobin degradation, conjugated by the liver, essential for elimination; ineffective processing can lead to jaundice.

Red Blood Cell (RBC) Degradation and Liver Role

  • RBC Lifecycle: Old or defective RBCs removed by splenic macrophages; bilirubin transported to the liver.

Liver Disorders Overview

Table of Liver Diseases

  • Viral: Hepatitis A-E, Epstein-Barr, cytomegalovirus, arboviruses, arenaviruses.

  • Metabolic: Hemochromatosis, biliary obstruction (e.g., gallstones), sclerosing cholangitis, biliary atresia.

  • Vascular: Portal vein thrombosis, Budd-Chiari syndrome.

  • Parasitic: Schistosomes, liver flukes, and more.

  • Autoimmune: Autoimmune hepatitis, primary biliary cirrhosis.

  • Miscellaneous: Polycystic liver disease, bacterial infections, and cryptogenic cases.

Cirrhosis

  • Regenerative Ability: The liver can regenerate but repetitive insults lead to scarring and possible loss of function.

  • Progression: Scarring begins as fibrous tissue; severe insults could result in fulminant liver failure.

Liver Function Tests (LFTs)

  • Nature of Tests: LFTs assess liver function indirectly; more accurately termed as liver damage tests.

  • Common Tests:

    • Serum Aminotransferases (AST and ALT): Indicators of parenchymal damage.

    • Serum Bilirubin: Indicates cholestasis.

    • Alkaline Phosphatase (ALP) and GGT: Indicators of biliary obstruction.

    • Serum Albumin: Reflects synthetic capacity.

    • Prothrombin Time (INR): Reflects clotting ability.

    • Serum Virology: Important for comprehensive assessment unless cholestasis is indicated.

Aminotransferases

  • Key Types: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

  • Liver Concentration: Enzyme activity in the liver can be 10,000 times that in the blood under normal conditions.

Interpretation of Aminotransferases

  • AST/ALT Ratio:

    • An AST/ALT ratio > 2 can indicate mitochondrial damage, commonly due to alcohol.

    • Elevated AST/ALT suggests liver disease (viral infection, autoimmune conditions, toxin exposure).

  • Muscle Damage: Conditions like rhabdomyolysis can also elevate AST/ALT levels but are distinguishable by specific markers.

Paracetamol-Induced Liver Damage

  • Toxicity: Acute overdose (around 10g) can lead to acute liver failure (ALF).

  • Mechanism: Conjugation pathways get overwhelmed, resulting in destructive metabolites damaging liver parenchyma.

  • Treatment: N-acetylcysteine infusion can replenish hepatic glutathione; emergency liver transplant may be needed in severe cases.

Alkaline Phosphatase (ALP)

  • Isoenzyme Sources: Liver and bone isoenzymes can both contribute to elevated levels in the blood; differentiation is necessary.

  • Clinical Relevance: Elevated in conditions like cirrhosis and biliary obstruction (e.g., gallstones).

Gamma-Glutamyl Transferase (GGT)

  • Function: A cytosolic enzyme released upon liver parenchyma damage.

  • Alcohol-Related Damage: A primary marker for alcohol-induced hepatic damage.

Plasma Proteins

  • Synthesis: Liver synthesizes approximately 12g of albumin daily; critical for maintaining osmotic pressure in the blood.

  • Transportation: Albumin also carries hydrophobic molecules like fatty acids.

  • Kidney Disease: Loss of albumin in urine due to kidney conditions can increase demand for albumin synthesis by the liver.

Conclusions on Liver Function Tests (LFTs)

  • Utility: While useful, LFTs have limitations and may not provide complete prognostic value alone.

  • Additional Measures Needed: Often require imaging or other tests for comprehensive analysis.

  • Dynamic Circumstances: Test results can reflect transient scenarios that may not persist over time.