Liver Functions in Healthy Animals

Learning Outcomes

  • Describe the structure and function of the liver in healthy animals:
    • Recognize the cellular organization of the liver and its relationship to liver function in healthy animals.
    • Explain the synthesis of bile salts and the production of bile.
    • Explain the structure and function of the gallbladder and biliary (duct) system in healthy animals.
    • List the testable liver enzymes and their roles and locations within the liver.
    • Review the various liver metabolic pathways involved in carbohydrate, lipid, and protein metabolism.
    • Discuss key liver enzymes and their roles in the metabolism of carbohydrates, protein, and lipids.

The Liver: Structure and Function

The Lobule & Sinusoids

  • The lobule is the functional unit of the liver, shaped hexagonally.
  • Each lobule consists of cords of hepatocytes:
    • Hepatocytes have:
      • Sinusoidal membranes with microvilli facing the sinusoid.
      • Biliary membranes with tight junctions to adjacent hepatocytes.
  • In hepatic sinusoids, oxygen-rich blood from the hepatic artery mixes with nutrient-rich blood from the portal vein.
  • Portal triads are located at the vertices of the lobules.

Functional Organization of the Liver

  • Divided into three zones (metabolic zonation):
    • Zone 1: Most peripheral, best perfused, access to oxygen-rich blood.
    • Zone 2: Pericentral, intermediate perfusion, great regeneration capacity.
    • Zone 3: Farthest from portal triad, lowest perfusion; contains high concentrations of P450 enzymes crucial for drug metabolism.
  • Endothelial cells of hepatic sinusoids allow fluid and proteins to leak through, maximizing exchange between hepatocytes and blood.

Key Functions of the Liver

  • Digestion Functions:
    • Bile production for fat digestion.
  • Metabolic Functions:
    1. Fat Metabolism:
      • Fatty acid synthesis, lipid transport (VLDLs), and ketogenesis.
    2. Carbohydrate Metabolism:
      • Glycogenesis, gluconeogenesis, glycogenolysis, glucose homoeostasis.
    3. Protein Metabolism:
      • Deamination of amino acids, urea formation, plasma protein synthesis, amino acid conversion.
    4. Detoxification/Excretion:
      • Drugs, hormones, bilirubin elimination.
    5. Storage:
      • Vitamins, minerals, trace elements.

Bile Production and Function

Bile Composition and Synthesis

  • Bile consists of:
    • Water (95%), bile salts, phospholipids, cholesterol, bicarbonate, proteins, bilirubin, and sodium.
  • Bile Salts Synthesis:
    • Synthesized from cholesterol in hepatocytes with cholesterol 7α-hydroxylase as the rate-limiting enzyme.
  • Bile salts promote digestion and excretion of waste (bilirubin, excess cholesterol).

Bile Canaliculi and Gallbladder Function

  • Bile components are secreted into bile canaliculi via active transport.
  • Bile concentrations in the gallbladder through sodium absorption, followed by chloride and water.
  • Gallbladder releases bile into the duodenum for fat digestion.

Carbohydrate Metabolism in the Liver

  • Key Metabolic Processes:
    • Glycogenesis: Conversion of glucose to glycogen for storage, regulated by insulin.
    • Glycogenolysis: Breakdown of glycogen to glucose during fasting.
      • Conversion requires Glucose-6-Phosphatase, specific to liver cells.
    • Gluconeogenesis: Production of glucose from non-carbohydrate sources during fasting.
      • Main precursors: amino acids, glycerol, lactate.

Lipid Metabolism in the Liver

  • Lipogenesis: Synthesis of fatty acids from excess glucose and amino acids, regulated by insulin.
  • Lipolysis: Breakdown of triglycerides into free fatty acids (FFAs) and glycerol, occurring during fasting.
  • Beta-Oxidation: FFA breakdown in mitochondria to produce energy via Acetyl-CoA.
  • Ketone Bodies Formation: During low glucose availability, FFAs are converted into ketones for energy.

Protein and Amino Acid Metabolism

  • Amino acids undergo:
    • Transamination: Transfer of amino groups to produce new amino acids.
    • Deamination: Removal of amino groups, producing ammonia and keto-analogues.
  • Ammonia is converted to urea for excretion due to its toxicity.

Testable Liver Enzymes

  • Important for diagnostic evaluations of liver function:
    • ALT (Alanine Aminotransferase), AST (Aspartate Aminotransferase), LDH (Lactate Dehydrogenase), etc.

Clinical Relevance

  • Accumulation of ammonia due to liver failure can lead to Hepatic Encephalopathy, resulting in neurotoxicity and severe neurological symptoms.