#Functions of the liver

#Outline the functions of the liver

#Immune functions

• Kuppfer cells
  • microorganisms ingested via the gut travel through the portal vein to the liver where they are phagocytosed by Kuppfer cells
  • Kuppfer cells can initiate an inflammatory response
• Synthesis of complement, CRP, acute phase reactants (e.g. fibronectin), and cytokines
• Immunoglobulins (IgG/IgA) are secreted in bile

#Reservoir for blood

The liver can release 250ml of blood into the venous circulation in response to sympathetic-mediated portal venous vasoconstriction.

#Synthetic functions

Synthesises 90% of all proteins which are secreted into circulation, for example:

• Albumin
  • predominant determinant of oncotic pressure
  • also has various immunomodulatory properties
• Globulins
  • alpha1 - e.g. alpha1 antitrypsin
  • alpha2 - e.g. alpha2 macroglobulin
  • beta - e.g. beta2 microglobulin
  • NB gamma globulins (immunoglobulins) are NOT made in the liver
• Clotting factors: all except factors III (tissue factor), IV (calcium), VIII and vWF
• Immunoligical proteins: complement, CRP, cytokines, acute phase proteins
• Liver enzymes

#Exocrine functions

• 1L bile is produced per day, which is concentrated to 200ml in the gallbladder
• Contains bile salts which emulsif dietary lipids into small droplets that are penetrated by pancreatic lipase, allowing absorption of fats and fat soluble vitamins (A, D, E, K)
• Bile salts reabsorbed in terminal ileum and recirculated to the liver

#Endocrine functions

• Hormone secretion
  • angiotensinogen
  • thrombopoietin
  • IGF-1
• Hormone activation
  • T4 converted to T3, or inactive rT3
  • 25-hydroxylation of vitamin D
• Hormone inactivation
  • many - ADH, aldosterone, insulin

#Metabolic functions

• Carbohydrates
  • contains glycogen
  • glycogen synthesis - mainly from lactate/pyruvate
  • glycogenolysis and gluconeogenesis → glucose production
  • glycolysis → produces CO2 + water + ATP
• Lipids
  • beta oxidation of free fatty acids → acetyl CoA → energy
  • triglyceride and cholesterol synthesis from excess glucose
    • LDL/VLDL/HDL synthesised form triglycerides and cholesterol
  • ketone synthesis from free fatty acids and acetyl CoA
• Proteins
  • deamination of amino acids
    • to ketoacids
    • to ammonia, which is converted to urea or glutamine in hepatocytes
  • ketoacids
    • used to synthesise other amino acids
    • used as an energy source
• Drugs/toxins
  • Phase I - modification by oxidation, reduction, or hydrolysis
  • Phase II - conjugation
  • Phase III - excretion into bile
  • Phase I and II reactions generally increase water solubility and increase renal excretion

#Storage functions

The liver stores various important compounds such as iron, copper, and fat soluble vitamins (A, D, E, K).