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At rest, the intracellular concentration of free calcium ions (Ca2+) is kept at 0.1 μM. During excitation, a transient rise of up to 10 μM elicits contraction in muscle cells (electromechanical coupling) and secretion in glandular cells (electrosecretory coupling).

The cellular content of Ca2+ is in equilibrium with the extracellular Ca2+ concentration (approx. 1000 μM), as is the plasma protein- bound fraction of calcium in blood. Ca2+ may crystallize with phosphate to form hydroxyapatite, the mineral of bone.

Osteoclasts are phagocytes that mobilize Ca2+ by resorption of bone. Slight changes in extracellular Ca2+ concentration can alter organ function: thus, excitability of skeletal muscle increases markedly as Ca2+ is lowered (e.g., in hyperventilation tetany).

Three hormones are available to the body for maintaining a constant extracellular Ca2+ concentration:

• Vitamin D
• Parathormone
• Calcitonin

Vitamin D hormone

Vitamin D hormone is derived from vitamin D (cholecalciferol). Vitamin D can also be produced in the body; it is formed in the skin from dehydrocholesterol during irradiation with UV light. When there is lack of solar radiation, dietary intake becomes essential, cod liver oil being a rich source.

Metabolically active vitamin D hormone results from two successive hydroxylations: in the liver at position 25 (
calcifediol) and in the kidney at position 1 (
calcitriol = vit. D hormone). 1-Hydroxylation depends on the level of calcium homeostasis and is stimulated by parathormone and a fall in plasma levels of Ca2+ or phosphate.

Vit. D hormone promotes enteral absorption and renal reabsorption of Ca2+ and phosphate. As a result of the increased Ca2+ and phosphate concentration in blood, there is an increased tendency for these ions to be deposited in bone in the form of hydroxyapatite crystals. In vit. D deficiency, bone mineralization is inadequate (rickets, osteomalacia).

Therapeutic use of Vitamin D

Therapeutic use aims at replacement. Mostly, vit. D is given:

• in liver disease calcifediol may be indicated
• in renal disease calcitriol

Effectiveness, as well as rate of onset and cessation of action, increase in the order vit. D. < 25-OH-vit. D < 1,25-di-OH-vit. D.

Overdosage may induce hypercalcemia with deposits of calcium salts in tissues (particularly in kidney and blood vessels): calcinosis.

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Parathormone

The polypeptide parathormone is released from the parathyroid glands when plasma Ca2+ level falls.

• It stimulates osteoclasts to increase bone resorption; in the kidneys
• it promotes calcium reabsorption, while phosphate excretion is enhanced

As blood phosphate concentration diminishes, the tendency of calcium to precipitate as bone mineral decreases. By stimulating the formation of vit. D hormone, parathormone has an indirect effect on the enteral uptake of Ca2+ and phosphate. In parathormone deficiency, vitamin D can be used as a substitute that, unlike parathormone, is effective orally.

Calcitonin

The polypeptide calcitonin is secreted by thyroid C-cells during imminent hypercalcemia. It lowers plasma Ca2+ levels by inhibiting osteoclast activity.

Therapeutic use – Its uses include hypercalcemia and osteoporosis. Remarkably, calcitonin injection may produce a sustained analgesic effect that is not restricted to bone pain.

Hypercalcemia

Hypercalcemia can be treated by:

• administering 0.9% NaCl solution plus furosemide (if necessary)
  to increase renal excretion
• the osteoclast inhibitors calcitonin, plicamycin, or clodronate (a bisphosphonate)
  to lower bone calcium mobilization
• the Ca2+ chelators EDTA sodium or sodium citrate
• glucocorticoids