Liver Functions & Diagnosis

Liver Function

Overview

  • Course: MMSC436-636

  • Instructor: Dr. Sam Biswas

Liver Structure

  • Blood Supply

    • Portal Vein: Contributes 80% of blood supply.

    • Hepatic Artery: Contributes 20% of blood supply.

  • Venous Drainage

    • Right and left hepatic veins.

Liver Cell Structure

  • Liver Cells: Composed of cords (lamina) and contain:

    • Hepatic Sinusoids: Where blood flows and exchanges occur.

    • Central Vein: Collects blood from sinusoids.

    • Bile Ducts: Transport bile to gallbladder.

Biochemical Functions of the Liver

Hepatic Excretory Function

  • Urea Synthesis: Conversion of ammonia to urea.

  • Excretion of Ammonia: Toxic byproduct of protein metabolism.

  • Gluconeogenesis: Conversion of alanine and pyruvate to glucose.

  • Glycogen Management: Synthesis, storage, and breakdown.

Hepatic Synthetic Function

  • Protein Synthesis:

    • Plasma Proteins: Albumin, transthyretin, immunoglobulins, ceruloplasmin, α1-antitrypsin, α-fetoprotein.

    • Coagulation Proteins: Essential for blood clotting.

Hepatic Metabolic Function

  • Ammonia Metabolism: Detoxification of ammonia.

  • Xenobiotic Metabolism: Breaking down drugs and toxins.

Lipid Synthesis

  • Lipoproteins, Triglycerides, Cholesterol: Synthesis and regulation.

  • Bile Acids and Ketones: Produced from lipid metabolism.

Albumin

  • Normal Level: 3.5 - 5.5 g/dL.

  • Function: Maintains oncotic pressure; if low, can lead to edema (fluid accumulation in tissues).

  • Role in Edema: Decreased albumin levels lead to hypotonic conditions, causing fluid to shift from blood vessels to tissue spaces.

Bilirubin Metabolism

Overview

  • Production: From breakdown of senescent red blood cells (hemoglobin to heme to bilirubin).

  • Transport: Bilirubin binds to albumin for transport to liver.

  • Conjugation: In liver, bilirubin binds with glucuronic acid to form water-soluble conjugated bilirubin.

Pathway of Bilirubin

  1. Production: Heme → Biliverdin → Bilirubin.

  2. Transport to Liver: Bilirubin-albumin complex enters liver.

  3. Conjugation in Liver: With UDP-glucuronic acid to form conjugated bilirubin.

  4. Excretion into Bile: Bile carries conjugated bilirubin to intestines.

  5. Metabolism in Gut: Converted to urobilinogen by bacteria.

Types of Bilirubin

  • Unconjugated (Indirect): Water insoluble; bound to albumin.

  • Conjugated (Direct): Water soluble; excreted in urine.

Jaundice

  • Definition: Yellowing of skin, sclera, and mucous membranes due to elevated bilirubin levels.

  • Classifications:

    • Prehepatic: Due to excessive hemolysis.

    • Hepatic: Liver disease or dysfunction.

    • Posthepatic: Obstruction of bile flow (gallstones or tumors).

Liver Diseases

Cirrhosis

  • Description: Scar tissue replaces healthy liver tissue, impeding function.

  • Common Causes: Chronic alcoholism, viral hepatitis (B, C).

Drug- and Alcohol-Related Disorders

  • Statistics: Drug-induced liver disease accounts for 1/3 to 1/2 of acute liver failure cases.

  • Types of Alcoholic Liver Disease:

    • Fatty Liver: Mild; reversible with cessation.

    • Alcoholic Hepatitis: Indicates liver damage.

    • Alcoholic Cirrhosis: Severe damage; poor prognosis.

Definitions

  • Jaundice: Yellow discoloration due to high bilirubin.

  • Kernicterus: Brain damage from high bilirubin in infants.

  • Conjugated Bilirubin: Water soluble; indicates liver processing ability.

  • Unconjugated Bilirubin: Water insoluble; byproduct of hemoglobin breakdown.

Hyperbilirubinemia

Causes

  • Prehepatic: Increased hemolysis.

  • Hepatic: Transport or conjugation failure.

  • Posthepatic: Bile duct obstruction.

Neonatal Jaundice

  • Benign Jaundice: Common, resolves without treatment.

  • Pathologic Jaundice: Abnormal, persistent; requires medical intervention.

    • Common Causes: Hemolytic disease, infections.

Measurement of Bilirubin

  • Bilirubin Types: Direct (conjugated, water soluble) and Indirect (unconjugated, water insoluble).

  • Methods: Use of diazotized sulfanilic acid, colorimetric tests.

  • Reference Ranges in Serum:

    • Conjugated: 0-0.2 mg/dL.

    • Unconjugated: 0.2-0.8 mg/dL.

    • Total: 0.2-1.0 mg/dL.

Assessment of Liver Function

Enzymes

  • Aminotransferases (ALT and AST): Indicators of hepatocyte injury.

  • Liver Function Tests: Measure bilirubin levels, assess enzyme levels.

Hepatitis

  • Causes: Viral, drug-induced, autoimmune, toxins.

  • Types: A, B, C, D, E with various transmission routes and impacts.

Bile Production

  • Components: Bile acids, cholesterol, pigments.

  • Production: 3L daily; principal pigment - bilirubin.

Urobilinogen Formation

  • From bilirubin metabolism by gut bacteria, indicates liver function and health.