Revision Resources

Calcium Homeostasis

July 25, 2016

The RCEM Basic Science curriculum states the following as required knowledge with regards to calcium homeostasis:

  • Functions of calcium in health
  • Physiological actions of calcium
  • Transportation of calcium (ionised, complexed, bound)
  • Factors affecting calcium handling: PTH, calcitonin and vitamin D3 and their effects on kidney, bone + small intestine
  • Foodstuffs rich in calcium
  • Sites of calcium transfer along the nephron in health
  • Effect of PTH upon renal calcium handling

Physiological Actions of Calcium

Calcium rich foods include: cheese, milk, yoghurt, fish, some vegetables and nuts.

Calcium is essential for:

  • enzymatic reactions
  • intracellular signalling
  • nerve conduction
  • skeletal, cardiac and smooth muscle contraction
  • the release of neurotransmitters
  • the release of exocrine and endocrine hormones
  • blood clotting
  • bone mineralisation

Transportation of Calcium

Blood calcium levels in the extracellular fluid are kept within a very narrow range to maintain normal physiological processes:

  • 40% of serum calcium is bound to albumin
  • a further 10% is bound to other plasma proteins
  • the rest is in a unbound ionised form

Only unbound ionised calcium is physiologically active.

Renal Handling of Calcium

Only ionised Ca2+ is filtered through the glomerulus.

About 70% is reabsorbed in the proximal tubule by diffusion, Ca2+ activated ATPase and the Ca2+/Na+ antiporter.

About 20-25% is reabsorbed passively in the loop of Henle.

About 5 – 10% is reabsorbed in the DCT against an electrochemical gradient.

Less than 0.5% is reabsorbed in the collecting ducts against an electrochemical gradient.

Hormonal Regulation of Calcium Homeostasis

Calcium homeostasis is primarily controlled by three hormones: parathyroid hormone from the parathyroid gland, vitamin D from the diet and skin, and calcitonin from the thyroid gland.

45_11CalciumHomeostasis_L

Parathyroid Hormone (PTH)

Synthesised by chief cells in the parathyroid gland.

Released in response to:

  • Falling plasma Ca2+ levels
  • Rising plasma PO43- levels (indirectly by its binding to ionised calcium and thereby effective reduction of blood calcium levels)

Release is inhibited by:

  • Normal/rising plasma Ca2+ levels
  • Hypomagnesaemia

Acts to:

  • increase calcium and phosphate resorption from bone (via indirect upregulation of osteoclast activity)
  • increase calcium reabsorption in the distal tubule of the nephron (by activating Ca2+ entry channels in the apical membrane and the Ca2+ ATPase pump on the basolateral membrane)
  • increase phosphate excretion by inhibiting reabsorption in the proximal tubule of the nephron
  • inhibit renal bicarbonate reabsorption stimulating a metabolic acidosis which favours dissociation of calcium from plasma proteins
  • stimulate 1-alpha-hydroxylase in the kidneys to produce activated vitamin D
  • indirectly increase calcium and phosphate absorption in the small intestine (via activated vitamin D)

Calcitonin

Secreted by parafollicular cells in the thyroid gland.

Secreted in response to rising or high plasma Ca2+ levels.

Acts to:

  • Inhibit reabsorption of calcium and phosphate in the kidneys
  • Inhibit osteoclast activity and resorption of calcium and phosphate from bone

Vitamin D (Cholecalciferol)

Absorbed by the small intestine as part of the diet or synthesised from cholesterol in skin.

Cholecalciferol is converted to calcifediol by 25-hydroxylase in the liver, and calcifediol to activated vitamin D (1, 25 – dihydroxycholecalciferol or calcitriol) by 1-alpha-hydroxylase in the kidney.

1-alpha-hydroxylase is stimulated by parathyroid hormone (PTH) and by low plasma PO43-.

Activated vitamin D acts to:

  • increase calcium and phosphate absorption in the small intestine (the main action)
  • increase renal calcium reabsorption (in the distal tubule via activation of a basolateral Ca2+ ATPase pump)
  • increase renal phosphate reabsorption
  • inhibit 1-alpha-hydroxylase activity in the kidneys (negative feedback)
  • affect bone remodelling to bring about the conditions of high calcium and phosphate optimum for bone remineralisation
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