The liver has 5 main functions:
Synthesis
Storage
Metabolism
Immunological function
Bile (both nutritional and excretory)
Synthesis
90% of plasma proteins (albumin, factors, compliment)
Regulatory proteins (thrombopoetin, angiotensinogen, herceptin)
Nutrients (gluconeogenesis, ketones, non-essential amino acids)
Storage
Energy (glycogen and lipid droplets)
Fat soluble vitamins (ADEK + B12)
Minerals (ferritin, copper)
Blood (25% of total blood volume)
Metabolism
Glucose \(\leftrightarrow\) Glycogen
Triglycerides \(\leftrightarrow\) FFAs \(\to\) ketones
Amino acids \(\to\) ammonia + \(\alpha\)-keto acid
Lactate \(\to\) glucose
Ammonia \(\to\) urea
Phase 1 + phase 2 metabolism of xenobiotics
Immunological
Synthesis of compliment
\(\uparrow\)herceptin \(\to\ \ \downarrow\)ferroportin to deny iron to bacteria
Kuffner cells (liver macrophages) phagocytose opsonised pathogens
IgA and IgG in bile
Excretion (via bile)
Bile acids (95% enterohepatically cycled)
Cholesterol (1g/day)
Conjugated bilirubin
Drugs (ceftriaxone, apixaban, digoxin)
Heavy metals (lead, arsenic)
Composition
95% water, 5% solutes
Organic solutes: bile salts (40mM), cholesterol (4mM), conjugated bilirubin (2mM), lipids, de minimus protein. Bile salts formed from neutralization of bile acids; primary = made by hepatocytes, secondary = made by intestinal bacteria
Inorganic solutes: similar ionic profile to plasma
Formation of bile
95% of bile salts reabsorbed in terminal ileum
Recirculate to hepatocytes and actively transported into bile
H2O follows by osmosis ("bile-salt dependent")
Other substances (conjugated xenobiotics, bilirubin) are also actively excreted, with H2O following by osmosis ("bile-salt independent")
Bile ducts \(\to\) water added
Gall bladder \(\to\) ions + H2O reclaimed, concentrating bile
Functions of bile
Emulsify lipids: \(\uparrow\)SA \(\to \ \uparrow\)lipid absorption + \(\uparrow\)absorption of fat-soluble vitamins
Excrete xenobiotics, cholesterol, bilirubin
Immune functions (IgA and IgG)
Growth factors for enterocytes
Synthesis failure
Hypoalbuminaemia
Thrombocytopenia and macrocytic anaemia
Coagulopathy
Storage failure
Hypoglycaemia
Metabolism failure
Accumulation of lactate
Accumulation of ammonia (hepatic encephalopathy)
Accumulation of drugs normally hepatically conjugated
Accumulation of unconjugated bilirubin
Immunological
Loss of compliment \(\to\) susceptibility to sepsis
Excretion (via bile)
Accumulation of conjugated bilirubin
Accumulation of drugs normally excreted in bile
Sources
Protein deamination: amino acid \(\to\ \ \alpha\)keto acid + ammonia
Purine metabolism in skeletal muscle
Renal ammoniagenesis from glutamate
Distribution
98% ionized and largely ion trapped
Metabolism
Exclusively in liver
Ammonia + CO2 \(\to\) urea
Elimination
Urea mostly excreted renally
~15% enterohepatically cycled (metabolized by flora back to ammonia and returned by first-pass to the liver; lactulose diverts bacterial metabolism)