The past two decades witnessed tremendous progress in our knowledge of the genetic and biochemical control of mineral metabolism. Clinical application of these discoveries has led to significant and practical improvements in diagnosis and treatment of disordered bone mineral metabolism as well as analysis of bone mass in children and adolescents.
Maintenance of calcium homeostasis is a complex dynamic process involving intestinal calcium absorption and excretion, renal filtration and reabsorption, and skeletal storage and mobilization (Figure 8-1).
The dynamics of calcium homeostasis in a normal adult. In growing children intestinal calcium absorption and skeletal deposition are increased.
Circulating calcium. Only 1% of total body calcium is within extracellular fluid (ECF) and soft tissues. Approximately 50% of total serum calcium is in the ionized form (Ca2+) at normal serum protein concentrations and represents the biologically active component of the total serum calcium concentration. Another 8% to 10% is complexed to organic and inorganic acids (eg, citrate, sulfate, and phosphate); together, the ionized and complexed calcium fractions represent the diffusible portion of circulating calcium. Approximately 40% of serum calcium is protein bound, primarily to albumin (80%) but also to globulins (20%), and is biologically inactive. Protein-bound calcium provides a readily available reserve of calcium should the acute need for increased ionized calcium arise.
Sudden changes in the distribution of calcium between ionized and bound forms may cause symptoms of hypocalcemia. Increases in ECF concentration of anions, such as phosphate, citrate, bicarbonate, or edetic acid, will decrease Ca2+ through chelation. Alkalosis increases the affinity of albumin for calcium and thereby decreases the concentration of Ca2+. By contrast, acidosis decreases the binding of calcium to albumin and increases Ca2+ concentrations.
Hence, physiologically relevant information is best obtained by determination of the Ca2+ concentration, particularly when evaluating patients who have abnormal circulating proteins or acid-base and electrolyte disorders (eg, total serum calcium will be low in a child with decreased serum albumin while the Ca2+ concentration will typically be normal). One widely used algorithm estimates that total serum calcium declines by approximately 0.8 mg/dL for each 1 g/dL decrease in albumin concentration.
The cytoplasmic concentration of Ca2+ affects many intracellular enzymes including adenylate cyclase, guanylate cyclase, troponin C, calmodulin, and protein kinase C. The normal intracellular calcium concentration can fluctuate from roughly 100 nM to greater than 1 µM, due to release from cellular stores or influx from ECF, and is generally less than the concentration in plasma (1 mM). Therefore, only minute amounts of calcium, either released from endoplasmic reticulum or from stimulated influx through calcium channels, are needed to raise the ...