The last two decades have seen great progress in our knowledge and understanding of the genetic and biochemical control of mineral metabolism. Moreover, our understanding of vitamin D action continues to extend well beyond the conventional roles in bone and mineral metabolism and now includes functions as a transcriptional regulator of immune function.
Clinical application of these discoveries has led to significant and practical improvements in diagnosis and treatment of disorders of mineral metabolism and analysis of bone mass in children and adolescents.
The 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 6-1).
The dynamics of calcium homeostasis in a normal adult. In growing children intestinal calcium absorption and skeletal deposition are increased.
Only 1% of the total body calcium is within extracellular fluids 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%). The protein-bound calcium is not biologically active but provides a readily available reserve of calcium should the need for increased ionized calcium arise acutely.
Sudden changes in the distribution of calcium between ionized and bound Ca2+ may cause symptoms of hypocalcemia. Increases in the extracellular fluid concentration of anions, such as phosphate, citrate, bicarbonate, or edetic acid, will chelate calcium and decrease ionized calcium. 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.
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 disorders1 (eg, total serum calcium will be low in a child with decreased serum albumin while the concentration of Ca2+ 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 is about 0.1 mmol/L, or about ten-thousandth the concentration in plasma. Therefore, only minute amounts of calcium, either released ...