How is calcium regulated?
Total body calcium is determined by the relative balance of calcium absorption and calcium excretion. The average adult diet contains 600–800 mg per day, although calcium supplementation can raise this to 2,000 mg per day. Absorption of this calcium in the small intestine is variable, and is determined by vitamin D levels. Typical absorption is 40–50% of dietary intake. Calcium is excreted in the gas-trointestinal tract and urine. Greater than 90% of calcium filtered by the glomerulus is reabsorbed by the nephron. Since the kidney cannot conserve calcium efficiently enough to compensate for low dietary intake or absorption problems, a negative calcium balance will result.
Calcium in the extracellular fluid is in constant equilib-rium with bone. The relative balance of bone deposition or resorption is determined by parathyroid hormone (PTH) and vitamin D. Vitamin D can be obtained from the diet or synthesized in the liver and skin, with the help of sunlight. Vitamin D is metabolized to the inactive form, 25(OH)D, by the liver, which is then metabolized to the active form, 1,25(OH)2D, by the kidney. Production of 1,25(OH)2D is enhanced by PTH, and possibly by hypocalcemia directly. 1,25(OH)2D stimulates calcium and phosphate absorption in the small intestine and calcium resorption from bone. 1,25(OH)2D also increases renal resorption of filtered calcium.
Hypocalcemia stimulates the parathyroid to secrete PTH. This peptide hormone causes resorption of calcium from bone, increased intestinal absorption of calcium, and increased resorption of filtered calcium in the kidney. PTH is involved in phosphate homeostasis, causing increased renal excretion. PTH excretion will increase in response to increased dietary phosphate because enhanced deposition of calcium and phosphate in bone leads to mild hypocalcemia. PTH also stimulates the production of 1,25(OH)2D.
Parathyroid-related protein (PTHrP) is functionally and structurally similar to PTH. This hormone is produced by numerous cell types, but little, if any, circulates in normal humans. Large tumors can produce enough PTHrP to cause significant blood levels and significant hypercalcemia.
Calcitonin is a peptide hormone that inhibits resorption of calcium from bone and in the kidney. Calcitonin is pro-duced in the thyroid, and its production is stimulated by hypercalcemia. The role of calcitonin in normal physiology is minimal, and there is no adverse outcome when it is absent following total thyroidectomy. Calcitonin is useful as a treatment for severe hypercalcemia.