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



·         Protective: immunity and detox

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



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)


·   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



Macronutrient concentrations


·   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)


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

·   Transamination (ALT, AST)

·   Uptake and release into circulation as required


·   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



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