At rest, the intracellular concentration of free calcium ions (Ca2+) is kept at 0.1 jM (see p. 128 for mechanisms involved). During excitation, a transient rise of up to 10 jM 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 jM), 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 hormone is derived from vitamin D (cholecalciferol). Vitamin D can also be produced in the body; it is formed in the skin from dehydrocholes-terol during irradiation with UV light. When there is lack of solar radiation, dietary intake becomes essential, cod liver oil being a rich source. Metaboli-cally active vitamin D hormone results from two successive hydroxylations: in the liver at position 25 (^ calcifediol) and in the kidney at position 1 (^ calci-triol = vit. D hormone). 1-Hydroxylation depends on the level of calcium homeo-stasis 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 hy-droxyapatite crystals. In vit. D deficiency, bone mineralization is inadequate (rickets, osteomalacia). Therapeutic Lullmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license.
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 hypercal-cemia with deposits of calcium salts in tissues (particularly in kidney and blood vessels): calcinosis.
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.
The polypeptide calcitonin is secreted by thyroid C-cells during imminent hypercalcemia. It lowers plasma Ca2+ levels by inhibiting osteoclast activity. Its uses include hypercalcemia and osteoporosis. Remarkably, calcitonin injection may produce a sustained analgesic effect that is not restricted to bone pain.
Hypercalcemia can be treated by (1) administering 0.9% NaCl solution plus furosemide (if necessary) ^ renal excretion f ; (2) the osteoclast inhibitors calcitonin, plicamycin, or clodro-nate (a bisphosphonate) ^ bone calcium mobilization | ; (3) the Ca2+chela-tors EDTA sodium or sodium citrate; as well as (4) glucocorticoids.
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