ABSTRACT
Calcium is a divalent cation that regulates cellular movement, hormone release, enzyme activity, and coagulation. Calcium also plays a role in cell injury and death.1 Ninety-nine percent of total body calcium is located in the bones and teeth. Normally, cytosolic calcium is very low, with a ratio of extracellular to intracellular ionized calcium of 10000:1.2
MEASURING CALCIUM
Normal serum calcium concentration is 8.8-10.3 mg/dl. The molecular weight of calcium is 40; in SI units the normal range is 2.2-2.6 mmol/L (4.4-5.2 mEq/L). Forty percent of serum calcium is protein-bound, primarily to albumin; an additional 10-15% is complexed to serum anions, such as bicarbonate, phosphate, and citrate. The remaining 45% is the physiologically active, ionized fraction.3 Normal ionized calcium is 4.0-5.2 mg/dl (1.0-1.3 mmol/L). Decreases in albumin lower total serum calcium without affecting ionized calcium. Likewise, increases in albumin or dramatic increases in globulins cause meaningless increases in total calcium, while the calcium regulatory mechanism maintains a normal ionized calcium.4,5 Increases in pH enhance calcium binding to albumin, lowering ionized calcium, whereas decreases in pH have the opposite effect. Free fatty acids, either from lipid infusions or endogenous lipolysis, increase calcium binding by albumin, lowering ionized calcium.6 Despite widespread use of formulas to adjust total calcium for albumin and pH, these have been shown to be poor predictors of ionized calcium. In patients where total calcium is borderline or there is suspicion of disordered protein-calcium binding, an ionized calcium should be checked.7,8
NORMAL REGULATION
A complex web of hormones tightly regulates the concentration of serum calcium. Unlike most electrolytes, the regulation of calcium balance begins with control of dietary absorption. In most situations 300-400 mg of dietary calcium is absorbed but since 200 mg is lost in gastrointestinal (GI) secretions, the net daily absorption is only 100-200 mg (Fig. 24.1). When patients are in calcium balance, all of that calcium is excreted in the
urine. Calcium metabolism is under the influence of parathyroid hormone (PTH), calcitriol, calcitonin, estrogen, and testosterone. The effect of estrogen and testosterone are complex, poorly understood, and will not be further discussed (Fig. 24.2).
