N1i / 25B15: Explain the role of the liver

25B15: Exam Report

Explain the role of the liver with respect to the following:

  1. Metabolic role in nutrition (30% of marks)
  2. Other metabolic and excretory functions (30% of marks)
  3. Storage and secretory functions (25% of marks)
  4. Immune functions (15% of marks)

48% of candidates passed this question.

Again, the question breakdown provided a clear structure and expected level of detail for each section.

Given the breadth of the question there was little time for candidates to give much more information other than a list of the roles under each category and a brief qualifying statement.

This is all that was required to score well.

High scoring answers included the following:

  1. An outline of carbohydrates, protein and lipid metabolism in the liver, including descriptions of catabolic and metabolic processes for each.
  2. An explanation of how the liver participates in drug biotransformation (phase 1+2 reactions and production of enzymes), lactate, ammonia, bilirubin and steroid hormone metabolism
  3. Role in nutrient and vitamin storage, blood storage and bile secretion.
  4. Role in phagocytosis, bacterial filtration in portal system and complement production.

N1i / 25B15: Explain the role of the liver

(a) Metabolic role in nutrition

  • Carbohydrates
    • Hepatic Glucostat – maintains normal BGLs
    • Glucose uptake into hepatocytes by GLUT2 transporters
      • Converts glucose → G6P (via glucokinase) so diffusion gradient is maintained for continuous glucose uptake
    • Glycogen synthesis + glycogenolysis
    • Glycolysis for ATP production
    • Gluconeogenesis from non-carbohydrate sources (lactate, pyruvate, glycerol, glucogenic aa’s)
  • Lipids
    • Lipolysis of TAG stores → glycerol & FFA’s
    • Beta oxidation – ATP production during starvation
      • FFA’s → Acetyl CoA → enters TCA cycle
    • Ketogenesis from condensation of excess FFA’s (from beta oxidation)
    • Lipoprotein synthesis as VLDL – transport to peripheral tissues
    • Cholesterol homeostasis via HMG-CoA
      • 80% synthesized cholesterol converted into bile
    • Bile acid production 1L/day – emulsify + absorption of fats, ADEK vitamins
  • Proteins
    • Anabolic
      • Synthesizes 90% of plasma proteins (albumin, clotting factors, α1/2 + βglobulins + transferrin for transport, CRP, angiotensinogen)
    • Catabolic
      • Amino acid degradation for energy production + aa’s recycling
        • By transamination, deamination, decarboxylation

(b) Other metabolic and excretory functions

  • Lactate metabolism → pyruvate via Cori cycle – acid-base balance
  • Ammonia metabolism → urea via Urea cycle
    • Excretes nitrogenous waste due to aa metabolism
  • Bilirubin conjugation with glucuronide by UDP-GT
    • ↑ hydrophilicity → actively excreted into bile
  • Biotransformation of endogenous + exogenous compounds – excretion into urine/ bile
    • Phase I reactions (oxidation, reduction, hydrolysis) – ↑ hydrophilicity of drugs
    • Phase II reactions (conjugation / glucuronidation / sulphation / acetylation) – makes more polar for excretion
  • Inactivation of steroid hormones (androgens, cortisol, aldosterone, T4) via Phase I/II → excretion

c) Storage and secretory functions

  • Storage
    • Metabolic fuel → glycogen (100g) + fat
    • Trace element → iron (as ferritin), copper, zinc, selenium
    • Vitamins → fat-soluble A, D, E, K + B12
    • Blood reservoir → 500mL (15% total blood volume)
  • Secretory
    • Synthesis of 25-hydroxycholecalciferol (calcitriol precursor) from skin cholecalciferol by vitamin D 25-hydroxylase
    • Synthesis of EPO
      • Adults – 10% of EPO (90% by kidneys)
      • Foetus – all EPO
    • Synthesis of thrombopoietin
    • Bile acid production 1L/day – emulsify + absorption of fats, ADEK vitamins

d) Immune functions

  • Complement proteins synthesis (innate immunity)
  • Kupffer cells in hepatic sinusoids
    • Part of RES (reticuloendothelial system)
    • Filters portal circulation by phagocytosis
    • Removes aged RBCs + leucocytes from circulation
    • Destroys bacteria/endotoxins in portal blood
  • Stellate cells → immune signalling

Author: Bonnie Lau