30. Liver function and metabolism slides

Liver Function & Metabolism

Overview

• Presented by Dr. Joe Quinn.

Learning Objectives

• Major Liver Functions:

  • List at least four key functions.

• Detoxification Processes:

  • Explain how the liver detoxifies toxins, drugs, and hormones.

• Vitamin Storage:

  • List at least three vitamins stored in the liver.

• Protein Metabolism:

  • Understand protein metabolism and the role of amino acids.

• Hormonal Control:

  • Outline how protein metabolism is regulated hormonally.

• Nitrogen Balance:

  • Indicate how nitrogen balance is measured and conditions affecting it.

• Lipid Metabolism:

  • Discuss lipid types and regulation of blood lipid levels.

  • Understand dyslipidemia and its health implications.

The Liver

Anatomy & Functions

• Largest Organ:

  • Comprises about 2% of total body weight (approximately 1.5 kg).

• Key Functions:

  1. Filtration and storage of blood.

  2. Metabolism of carbohydrates, fats, proteins, hormones, foreign chemicals.

  3. Formation of bile.

  4. Storage of vitamins and iron:

     • Vitamin A: 10 months.

     • Vitamin D: 3-4 months.

     • Vitamin B12: Up to 1 year (but can extend to 4).

  5. Production of coagulation factors.

• Blood Supply:

  • Dual supply via:

    • Hepatic Artery: Carries oxygenated blood.

    • Portal Vein: Transports nutrient-rich blood from the gastrointestinal tract.

  • Blood flows through hepatic sinusoids to the central vein in liver lobule, then to the inferior vena cava via the hepatic vein.

Liver Structure

Functional Unit

• Liver Lobule:

  • Central vein empties into hepatic veins.

  • Composed of hepatocytes.

  • Sinusoids connect central vein with branches of hepatic artery and hepatic portal vein.

  • Bile is secreted into bile canaliculi, which empty into bile ducts.

  • Portal Triad comprises hepatic artery, portal vein, and bile duct.

  • Can store significant blood volumes; normal volume is 10% of total body volume.

• Blood Reservoir:

  • Can store up to 0.5-1 litre of blood in hepatic veins and sinuses during high right atrium pressure (e.g., cardiac failure).

Detoxification & Phagocytosis

Key Processes

• Ammonia Removal:

  • Via urea cycle; urea is excreted by kidneys.

• Ethanol Removal:

  • Alcohol dehydrogenase converts ethanol to acetaldehyde and NADH, which is further converted to acetyl CoA by peripheral tissues (skeletal muscle)

• Drug Metabolism:

  • First-pass effect influences drug activity. Bad problem - aspirin inhibits platelet function, hydrolysed to salicyclic acid

• Hormone Removal:

  • Liver excretes hormones into bile from plasma

• Küppfer Cells:

  • Phagocytic cells in the reticuloendothelial system.

Protein Metabolism

Functionality & Quantities

• Constituents:

  • Makes up 75% of body solids.

  • Diverse functions: structural, immune, transport, muscle contraction, communication, plasma oncotic pressure.

• Daily Requirements:

  • Recommended intake: 30-50g daily (0.75g/kg body weight).

Amino Acids

Categories

• Essential Amino Acids:

  • Threonine (Thr), Lysine (Lys), Methionine (Met), Arginine (Arg), Valine (Val), etc.

• Non-Essential Amino Acids:

  • Glycine (Gly), Alanine (Ala), Serine (Ser), Cysteine (Cys), etc.

• Blood Concentration:

  • Normal range: 35-65 mg/dl; rises post-meal.

  • Excess amino acids are taken up by the liver, will not accumulate in blood or tissue fluids

Amino Acids in Protein Metabolism

Transport Mechanisms

• Amino acids move in/out of cells via facilitated diffusion or active transport.

• Important for maintaining stable plasma concentrations, influenced by hormones (e.g., growth hormone, insulin).

Nitrogen Balance

Measurement & Implications

• Basic Concept:

  • Protein contains ~16% nitrogen.

  • Excretion: 90% via urine, 10% in feces.

• Measurement Formula:

  • Nitrogen in urine + 10% feces x 6.25 = Protein breakdown.

• Types of Nitrogen Balance:

  • Negative: Breakdown exceeds intake (e.g., starvation).

  • Positive: Intake exceeds breakdown (e.g., growth, recovery).

  • Neutral: Equilibrium.

Amino Acid Catabolism

Pathways

• Excess amino acids may be reutilised or degraded.

• Transamination:

  • Transfer of amino groups facilitated by specific enzymes (e.g., aminotransferases).

• Involves amino acids like glutamine as amino group donors.

Starvation and Protein Use

Energy Utilization

• Carbohydrates and fats primarily used for energy; protein reserves tapped in deficiency.

• Degradation can lead to issues like Noma in malnourished individuals.

Hormonal Control of Protein Metabolism

Key Hormones

• Growth Hormone: Increases protein synthesis.

• Insulin: Essential for cellular uptake of amino acids; reduces degradation.

• Glucocorticoids: Enhance protein breakdown, increasing plasma amino acids.

• Testosterone & Oestrogen: Promote protein deposition.

• Thyroxine: Affects metabolic rate, with marginal direct effects on protein metabolism.

Lipids Overview

Functions and Importance

• Energy Source: Provide 30-40% of daily caloric intake.

• Structural Role: Essential for membranes, bile acids, steroid hormones, etc.

• Surfactant Function: Important in lung alveoli integrity.

Liver and Lipid Metabolism

Synthesis and Degradation

• Degradation of fatty acids for energy.

• Synthesis of triglycerides from carbs and proteins; cholesterol and phospholipids from fatty acids.

Lipids Classification

Types of Fatty Acids

• Saturated: No double bonds (fully saturated with hydrogen).

• Monounsaturated: One double bond.

• Polyunsaturated: More than one double bond.

Lipoproteins and Lipid Transport

Mechanisms

• Free Fatty Acids Transport: Released from adipose tissue to other tissues.

• Lipoprotein Structure: Lipid and protein components facilitate transport.

• Types of Lipoproteins:

  • Chylomicrons: Transport dietary fats.

  • VLDLs: Transport triglycerides from liver.

  • LDLs: Main cholesterol carriers.

  • HDLs: Reverse cholesterol transport from tissues to liver.

Triglycerides

Formation and Role

• Formed from glycerol and fatty acids; mainly used for energy.

• Hydrolysed into fatty acids and glycerol for transport and oxidation in tissues.

Phospholipids

Structural and Functional Role

• Synthesized primarily in the liver; essential for membrane structures and function.

Cholesterol

Overview

• Absorbed from diet, synthesized in the liver.

• Vital for cell membranes and hormone production; plasma levels affected by diet and metabolism.

Transport of Lipids

Processes

• Lipids are absorbed and transported through the GIT, entering lymph as chylomicrons post-meal.

Dyslipidaemias

Health Risks

• Abnormalities in lipoprotein metabolism increase cardiovascular disease risks; include various genetic and secondary conditions.

Clinical Significance of Lipid Disorders

Associated Conditions

• Facial xanthomas and other signs indicate lipid disorders, highlighting risks for ischemic heart disease.

Atherosclerosis Development

Mechanism

• Damaged endothelium leads to monocyte and LDL accumulation; foam cell formation progresses to plaque and artery hardening.