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Calcium (Ca) is present largely (99%) in the skeleton
as the hydroxyapatite crystal of calcium phosphate [Ca10(PO4)10(OH)2].
Only the 1% to 2% that resides in recently deposited
and rapidly exchangeable surface bone, blood, and extracellular
fluid is readily mobilized. Calcium serves as an inter- and intracellular
messenger and is necessary for neuronal and neuromuscular communication,
muscular contraction, cardiac rhythmicity, enzyme function, clotting,
protein synthesis and secretion, and cellular proliferation. Intracellularly, calcium
is a second messenger that propagates signals that control cellular
activities such as gene transcription, cell division, growth, movement,
and function. Total serum calcium is composed of about 50% ionized
calcium (Ca2+), the physiologically active form,
about 40% calcium bound to albumin and globulins where
it is inert, and 10% is complexed to citrate, lactate,
bicarbonate, phosphate, or sulfate. Systemic acidosis decreases calcium
binding to albumin thus increasing serum Ca2+ levels,
while alkalosis increases calcium binding to albumin and lowers
Ca2+ values.
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Serum Ca2+ levels are maintained within narrow
limits by a complex integration of the plasma membrane Ca2+ sensing
receptor (CaSR); parathyroid hormone (PTH) and its receptor (PTH/PTH-related
protein [PTHrP]-R-PTHR1; calcitonin, the product
of the thyroidal parafollicular (C) cell and its receptor; and the vitamin
D hormone system acting upon the intestinal tract, bone, and kidney
(Fig. 542-1).1-3 As the serum Ca2+ concentration
increases, the CaSR on the chief cell of the parathyroid gland (PTG)
is activated and decreases PTH synthesis and release. Activation
of the CaSR in the distal renal tubule decreases reabsorption of
calcium and increases its urinary excretion. PTH stimulates osteoclastic
bone reabsorption and increases renal tubular synthesis of 1,25
dihydroxyvitamin D3 (calcitriol) and intestinal absorption
of calcium.
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Ca2+ enters cells through transmembrane calcium
channels. Intracellularly, Ca2+ is bound to calbindin
and calmodulin. Ca2+ leaves the cell through adenosine
triphosphate (ATP)-driven Ca2+ pumps and by exchange
for sodium (Na+) through H+-ATPase
and Na+-Ca2+ exchangers. In
the intestinal tract, calcium is absorbed in the duodenum, jejunum,
ileum, and colon through the enterocyte’s calcium transport
protein 1 (TRPV6), whose synthesis is stimulated
by calcitriol. Ca2+ is released from ...