Functions of the liver

This chapter tries to reapproximate the edges of  Section N1(i) from the 2017 CICM Primary Syllabus, which expects nothing less than the trainee "describe the functions of the liver." The objective commanded by this imperative statement is so vast that to address it in a single page would be overambitious even for the notoriously immoderate writer of Deranged Physiology (where "summary" chapters routinely run to 9,000 words). This section of the CICM syllabus really deserves to be split into several smaller sections to make it manageable, and to make it easier for the reader to ignore the parts they view as boring or irrelevant.  The older versions of the syllabus even suggested the section structure by dividing the functions of the liver into "storage, synthetic, metabolic, immunological and excretory". 

In historical exam papers the college has often asked for all of these to be "outlined" or "listed" in the space of a ten-minute SAQ answer:

"Testing breadth of knowledge rather than depth" was apparently the objective of these. What follows is therefore a superficial listing of the functions of the liver, grouped as logically as was afforded by the limitations of the famously logic-averse author. In case the reader values depth of knowledge as much as breadth, they can be referred to Kuntz & Kuntz (2008) who answer the CICM SAQ over about 40 pages of densely packed text.  For a much shorter alternative, the functions of the liver are summarised in a table from this review article by Ozougwu et al (2017) What follows is a similar attempt to squish a massive topic into a tiny space. Links of the main headings point to a chapter where each domain is thoroughly discussed.

  • Storage functions of the liver:
    • Metabolic fuel storage: glycogen (75g, 400kcal) and fat (75g, 600 kcal)
    • Vitamin storage: fat soluble A, D, E and K, as well as B12
    • Trace element storage: iron (as ferritin), copper, sink, selenium
    • Blood reservoir function: contains up to 27% of total blood volume
  • Synthetic functions of the liver:
    • Synthesis of 90% of blood proteins (albumin, clotting factors, complement)
    • Synthesis of regulatory molecules (thrombopoietin, angiotensinogen)
    • Synthesis of nutrients: glucose (gluconeogenesis), ketones, lipids (VLDL), cholesterol, non-essential amino acids
    • Synthesis of bile acids from cholesterol and urea from ammonia
    • Synthesis of bilirubin (by Kupffer cells)
  • Metabolic functions of the liver:
    • Carbohydrate metabolism: conversion to and from glycogen
    • Lipid metabolism: transformation into ketones or triglycerides
    • Protein metabolism: deamination or transamination of amino acids
    • Ammonia metabolism (into urea) and lactate metabolism (into glucose)
  • Immunological functions of the liver:
    • Synthesis of complement proteins (innate immunity)
    • Regulation of protein synthesis to hinder infection (eg. restriction of systemic iron carriage and reduced production of negative acute phase reactants)
    • Filtration of antigens from the blood by Kupffer cells and sinusoidal endothelial cells
  • Excretory functions of the liver:
    • Excrretion of bile acids (though 95% undergo reabsorption)
    • Excretion of cholesterol in the bile (800-1200mg/day)
    • Excretion of conjugated bilirubin in the bile
    • Excretion of some ions (mainly sodium)
    • Biliary excretion of drugs (ceftriaxone, apixaban, digoxin)
    • Biliary excretion of heavy metals (lead, arsenic, mercury, cadmium)

This structure is probably not especially conducive to learning. Consider:  when discussing the storage functions of the liver, one would come across glycogen. Then, when discussing the synthetic function of the liver, one would once again trip over glycogen (which is synthesised in the liver). When thinking about the metabolic functions of the liver, one would inevitably have to mention glycogen as a major source of hepatic glucose. In short, it must have seemed sensible to divide the functions of the liver into storage, synthesis, metabolism, etc, but conceptually it would probably be better to explain it in terms of its functional roles. In that way, everything pertaining to carbohydrate metabolism would be together, and more easily understood. Unfortunately the linked pages follow the old 2017 syllabus item, which asked the trainees to "describe the storage, synthetic, metabolic, immunological and excretory functions of the liver". To rearrange these entries into a more sensible structure is presently beyond the resources of this author. No system is perfect, as many of the things the liver does have multiple functions and there would inevitably be some repetition and overlap, but if the time ever comes, this could be an alternative system:

  • Role in macronutrient metabolism
    • Metabolic fuel storage: glycogen (75g, 400kcal) and fat (75g, 600 kcal)
    • Synthesis of nutrients: glucose (gluconeogenesis), ketones, lipids (VLDL), cholesterol, non-essential amino acids
    • Carbohydrate metabolism: conversion to and from glycogen
    • Lipid metabolism: transformation into ketones or triglycerides
    • Protein metabolism: deamination or transamination of amino acids
  • Role in micronutrient metabolism
    • Vitamin storage: fat soluble A, D, E and K, as well as B12
    • Trace element storage: iron (as ferritin), copper, sink, selenium
  • Role in blood purification and elimination of wastes
    • Metabolism of drugs
    • Elimination of cholesterol  (800-1200mg/day) by synthesis of bile acids from cholesterol (though 95% undergo reabsorption)
    • Elimination of ammonia by synthesis of urea
    • Elimination of heme (synthesis of bilirubin by Kupffer cells) and excretion of conjugated bilirubin in the bile
    • Excretion of some ions (mainly sodium)
    • Biliary excretion of drugs (ceftriaxone, apixaban, digoxin)
    • Biliary excretion of heavy metals (lead, arsenic, mercury, cadmium)
  • Role in electrolyte and acid-base balance
    • Metabolism of lactate
    • Synthesis of albumin (which is the main part of the anion gap)
  • Endocrine functions
    • Activation of vitamin D
    • Conversion of thyroxine (T4) to T3
    • Synthesis and secretion of 90% of blood proteins (albumin, clotting factors, complement)
    • Synthesis of regulatory molecules (eg. angiotensinogen)
  • Haematological functions
    • Blood reservoir function: contains up to 27% of total blood volume
    • Secretion of thrombopoietin
    • Synthesis of clotting factor proteins
  • Immunological functions
    • Synthesis of complement proteins (innate immunity)
    • Regulation of protein synthesis to hinder infection (eg. restriction of systemic iron carriage and reduced production of negative acute phase reactants)
    • Filtration of antigens from the blood by Kupffer cells and sinusoidal endothelial cells

References

Kuntz, Erwin, and Hans-Dieter Kuntz. "Biochemistry and functions of the liver." Hepatology Textbook and Atlas: History· Morphology Biochemistry· Diagnostics Clinic· Therapy (2008): 35-76.

Ozougwu, Jevas C. "Physiology of the liver." International Journal of Research in Pharmacy and Biosciences 4.8 (2017): 13-24.