Hypocalcemia

Excerpt

Calcium homeostasis in the body is a complex interplay between different hormones, regulatory proteins, receptors, and serum chemistries. The main factors that regulate calcium homeostasis in the body are parathyroid hormone (PTH), 1,25(OH)-vitamin D (activated vitamin D or calcitriol), fibroblast growth factor 23 (FGF23), calcitonin, calcium-sensing receptor (CaSR), serum calcium, and serum phosphorus.

Serum calcium concentration is maintained within a very narrow range. Approximately 45% of the body's calcium is bound to plasma proteins, primarily albumin. Approximately 15% is bound to small anions such as phosphate and citrate. And approximately 40% is in the free or ionized state, which is the active state. Most laboratories report total serum calcium concentration, which ranges between 8.5 to 10.5 mg/dL (2.12 to 2.62 mmol/L). Ionized calcium can also be measured, and the normal range is 4.65 to 5.25 mg/dL (1.16 to 1.31 mmol/L). Numbers below this range are considered to be hypocalcemic. Because the majority of body calcium is bound to albumin, total calcium should always be corrected for albumin level before the diagnosis of hypocalcemia is made. There is an approximately 0.8 mg/dL (0.25 mmol/L) drop in serum total calcium concentration for every 1 g/dL (10 g/L) reduction in the serum albumin concentration.

Calcium and phosphorus metabolism are closely linked. The primary hormonal regulators are PTH hormone, produced by the parathyroid glands, and calcitonin, produced by the thyroid C-cells. PTH increases calcium levels by increasing osteoclastic activity, while calcitonin does the opposite and inhibits osteoclasts. There are also many complex feedback loops, including those where calcium and activated vitamin D decrease PTH secretion, while elevated phosphorus levels increase PTH secretion. PTH and activated vitamin D also increase distal renal tubular reabsorption of calcium. PTH, FGF23, and Klotho (a regulatory protein that increases FGF23 activity) decrease serum phosphorus by inhibiting renal phosphorus absorption. Activated vitamin D increases phosphorus absorption from the intestine, renal tubules, and bones.

Disorders of calcium metabolism are encountered relatively frequently in routine clinical practice. Hypocalcemia is not seen as frequently as hypercalcemia is, but it can be potentially life-threatening if not appropriately recognized and promptly treated. Most hypocalcemia causes are acquired, but some are inherited. Clinical presentations can vary from asymptomatic to life-threatening arrhythmias or seizures.