Regulation of Calcium Balance

The total calcium concentration in extracellular fluid (ECF) is maintained within a narrow range of 8.5-10.5 mg/dl in adult humans, mean of 9.5 mg/dl (approximately 2.5 mM, 5 mEq/liter). In plasma, 35-40% of calcium is bound to macromolecular protein, especially albumin. Approximately 60-65% of plasma calcium is filtered at the glomerulus as ultrafilterable calcium [6]. Of the calcium that is ultrafiltered, about 10% is complexed as the calcium salts of bicarbonate, sulfate, and citrate.

Extracellular calcium homeostasis involves coordinated calcium absorption by the intestine, calcium resorption from bone, and calcium reabsorption by the kidney. The PTH-vitamin D axis plays a key role in calcium homeostasis, acting to normalize ECF calcium concentration. In a state of normal calcium balance, net intestinal calcium absorption and renal calcium excretion are approximately equal. The average adult human ingests 800 mg calcium daily. Approximately 600 mg of calcium is excreted in feces, and 200 mg enters the ECF. This extracellular pool equilibrates with bone calcium pools, and, to a lesser extent, with intracellular calcium pools. The final urine contains approximately 200 mg calcium daily (Fig. 1).

Diet

800mg Ca

Feces

600mg Ca

500mg

wu Urine

1OOOOmg

9800mg

200mg figure 1. Total body calcium balance. Net calcium movement as shown by dark solid arrow.

Feces

600mg Ca

500mg

500mg

Bone

9800mg wu Urine

1OOOOmg

200mg figure 1. Total body calcium balance. Net calcium movement as shown by dark solid arrow.

iPTH

tPTH

^ ^U, Serum Ca w w Concentration

FIGURE 2. Interactions of kidney, intestine, and bone in the regulation of calcium homeostasis.

With a fall in plasma calcium concentration, PTH secretion is stimulated. Parathyroid hormone stimulates renal tubular calcium reabsorption, increases skeletal calcium mobilization, and enhances renal production of 1,25-dihy-droxyvitamin D [l,25-(OH)2D], The increase in serum l,25-(OH)2D concentrations enhances intestinal calcium absorption and decreases renal calcium excretion. l,25-(OH)2D also acts directly on bone cells to stimulate skeletal calcium mobilization (Fig. 2). With occurrence of hypercalcemia, PTH secretion is suppressed, and calcitonin release is stimulated. Consequently, renal calcium excretion increases and skeletal calcium mobilization decreases. A decrease in plasma l,25-(OH)2D concentration, due to the fall in PTH concentration, leads to a decreased absorption of calcium in the intestine and decreased skeletal calcium mobilization (Fig. 2).

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