Serum and extracellular calcium concentrations in mammals are closely regulated within a narrow physiologic range that is optimal for the many normal cellular functions affected by calcium in many tissues (1,2). More specifically, it is the ionized component of serum calcium that is closely regulated, as it subserves the physiological functions of this divalent cation (Table 3). Ambient calcium is so close to its saturation point in the respect to phosphates that deviations in concentrations of either can cause precipitation. Intracellular calcium, which serves as second messenger in many signal transduction pathways, is also tightly controlled, but at concentrations several orders of magnitude lower than extracellular calcium. Extraskeletal calcium accounts for only 1% of the total body calcium and is primarily sequestered in bone (Table 4-6). The average diet can be considered to contain about 1 gm of calcium, but there are great variations. About 500 mg undergoes net absorption from the diet, and the unabsorbed and secreted components appear in the stool (Table 6-9). Approximately 10,000 mg/day is filtered at the glomerulus and most is reabsorbed by the renal tubules, with only a few hundred milligrams appearing in urine each day (Tables 10 and 11). The skeleton turns over about 250 mg/day of calcium, but there is wide variation. This turnover is attributed to a labile calcium pool near bone surfaces, but it is different to give anatomical assignment to either labile or non-labile calcium compartments. The turnover is mediated by bone-forming osteoblasts and bone resorbing osteoclasts. In disease states, the turnover can be increased (e.g., hyperparathyroidism) or decreased (e.g., hypoparathyroidism) with corresponding changes in blood and urinary calcium. The calcium regulating hormones that control this homeostatic system are PTH and vitamin D, which act at bone, kidney, and GI tract to increase serum calcium and calcitonin, which an correspondingly act to decrease serum calcium (Figure 1).
Table 3. Multiple biological functions of calcium
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Table 4. Distribution of Calcium
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Table 5. Bone Structure (cellular and non-cellular)
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Table 6. Blood Calcium - 10mgs/100 mls(2.5 mmoles/L)
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Table 7. Diet
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Table 8. Calcium Absorption (0.4-1.5 g/d)
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Table 9. Mechanisms of GI Calcium Absorption
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Approximately 50% of the total calcium in serum is ionized, with the rest bound primarily to albumin or complexed with counter-ions, including phosphates (Table 6) (1,2). The ionized calcium concentration averages 1.25 + 0.07 mmol/L and the total serum calcium concentrations range from 8.5 to 10.5 mg/dL. Since ionized calcium has the primary regulatory role, it is in turn the regulated component that maintains homeostasis. This regulation takes place through the complex interactions at their target organs of the primary calcium regulating hormones, parathyroid hormone (PTH), calcitonin (CT), and vitamin D and its metabolites (Tables 4-11). Other hormones participate, notable gonadal steroids.
Table 10. Urinary Calcium
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Table 11. Regulation of Urinary Calcium
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