2015A03 Outline the protective and regulatory functions of the liver.

 

List:

·       Protective: immunity and detox

·       Regulatory: macronutrient supply, blood volume, oncotic pressure, coagulation status

 

Protective:

Innate immunity

·  Filter portal blood

·  Kupffer cells: phagocytosis, cytokine secretion (IL-1, IL-6, TNF-α)

·  Synthesises complement (opsonization, lysis, chemotaxis)

·  Synthesises acute phase reactants (CRP activates complement, Ferritin, α1 antitrypsin)

Adaptive immunity

·  Kupffer cells: present antigens to TH cells

·  (Kupffer cells are macrophages lining the sinusoids)

Detoxification

·  Affects toxins and drugs

·  Oral route via portal blood = first pass metabolism. Barrier between gut and rest of body.

·  Other routes via hepatic arterial blood

·  Phase 1 reactions: oxidation, reduction, hydrolysis. By CYP450. Usually inactivates.

·  Phase 2 reactions: glucuronidation, sulfation, acetylation, methylation. Usually solubilizes

·  Large, lipid soluble metabolite -> bile, faeces

·  Small, water soluble metabolite -> urine

 

Regulatory:

Macronutrient concentrations

Carbohydrates:

·  Islet β-cell = glucostat, liver = major effector

·  Constitutive GLUT-2 = free glucose movement

·  Direction of glucose flow controlled by hexokinase activity, not portal blood [glucose]

·  Insulin -> ↑uptake, ↑trapping as G6P (↑hexokinase, glycogenesis, DNL, glycolysis)

·  Glucagon, cortisol, SNS -> ↑release (↓hexokinase, ↑glycogenolysis, gluconeogenesis, lipolysis)

Proteins:

·  Amino acid synthesis (↑insulin:glucagon) and breakdown (↓insulin:glucagon)

·  Transamination (ALT, AST)

·  Uptake and release into circulation as required

Lipids:

·  Glucose -> fatty acid when glucose in excess (↑fatty acid synthase)

·  Fatty acid -> ketones when ↑Acetyl-CoA:OAA ratio

·  Synthesises apolipoproteins

Oncotic pressure

·  Synthesises and recycles albumin. Stable 40g/L

·  Synthesises α and β globulins (not γ-globulin)

·  Regulates plasma oncotic pressure, blood volume

·  Minimizes transudation and oedema

Blood volume

·  Blood reservoir ~450mL

·  ↓Blood vol -> ↑α1 vasoconstriction of sinusoids-> autotransfusion ~200mL

·  ↑Blood vol -> ↓α1 vasoconstriction -> ↑capacitance (up to 1.5L in heart failure)

Red cell mass

·  Synthesises EPO: 10% in adult, near 100% in foetus

·  Degrades EPO

Coagulation status

·  Synthesises all coag proteins except vWF

·  Synthesises anticoag proteins C, S, AT3

·  Synthesises plasminogen

ECF volume

·  Synthesises angiotensinogen (regulate ECF [Na+], ECF water, blood volume via Angiotensin 2, aldosterone)

Calcium homeostasis

·  Activates Vit D -> 25-OH-Vit D

GIT absorption

·  Continuous synthesis of bile

·  Regulation of storage in and release from gallbladder is by CCK

·  Bile = salts + acids + cholesterol + lecithin

·  Transports lipid soluble substances into GIT for excretion

·  Emulsifies dietary lipids, ↑ absorption of lipids and ADEK

 

Addit: Usual classification of functions of the liver:

·       Metabolism: CHO, prot, lipids, ketones, alcohol

·       Excretion: bile, urea

·       Synthesis: plasma proteins, bile, coagulation related factors, bilirubin

·       Storage: glycogen, vitamins, metals

·       Hormonal: synthesis, activation, degradation

·       Haematological: blood reservoir, procoag + anticoag + fibrinolytic

·       Immunological: innate + adaptive

·       Detoxification: toxins and drugs