Liver Functions: Metabolism, Detoxification, Synthesis, Storage, and Immunity

The Liver: Metabolic Hub and Detoxifier

The liver performs >500 functions; key categories:

1. Metabolism

• Carbohydrates: Glycogenolysis, gluconeogenesis, glycolysis, glycogenesis – maintains blood glucose.
• Lipids: β-oxidation, ketogenesis, lipoprotein synthesis (VLDL, HDL), cholesterol synthesis/bile conversion.
• Proteins: Deamination, transamination, urea cycle (ammonia detox), synthesis of most plasma proteins.

2. Detoxification & Biotransformation

• Phase I (CYP450): Oxidation, reduction, hydrolysis – activate/inactivate drugs, toxins, steroids.
• Phase II (Conjugation): Glucuronidation, sulfation, glutathione, methylation, acetylation – increase water solubility for excretion.
• Phase III: Transporters (MDR1, MRP2) pump conjugates into bile/canaliculi.

3. Bile Production & Secretion

• ~500–1000 mL/day: bile salts, cholesterol, phospholipids, bilirubin, proteins.
• Emulsifies fats → enables pancreatic lipase action; absorbs fat-soluble vitamins.
• Enterohepatic circulation: 95% bile salts reabsorbed in ileum.

4. Storage

• Glycogen (~100 g), Vitamins A, D, B12, K, Iron (ferritin), Copper.

5. Synthesis

• Plasma proteins: Albumin (oncotic pressure), clotting factors (I, II, V, VII, IX, X, XI, XII), complement, acute-phase reactants.
• Hormones/precursors: IGF-1, thrombopoietin, hepcidin, angiotensinogen.

6. Immunity

• Kupffer cells (resident macrophages): phagocytose bacteria, endotoxin, debris from portal blood.
• NK cells, lymphocytes; acute-phase response.

7. Heme/Iron Recycling

• Senescant RBCs → bilirubin → conjugated → bile; iron → transferrin → marrow.

8. Cholesterol Homeostasis

• Synthesis (HMG-CoA reductase), conversion to bile acids, LDL receptor clearance, HDL reception (SR-B1).

Liver disease disrupts all these systems – hence multisystem manifestations.