Calcium is one of the most abundant and important minerals in the body. It is essential for skeletal integrity, and in its physiologically active form is responsible for cellular depolarization, muscle excitation/contraction, neurotransmitter release, hormonal secretion, and the function of both leukocytes and platelets.

Ninety-nine percent of body calcium is stored in bone. Of the <1% present in the circulation, 40% is bound to proteins such as albumin, 12% is complexed with anions such as phosphate and citrate, and 48% is ionized.¹ Serum calcium levels measure ionized, complexed, and protein-bound calcium. Ionized calcium is the physiologically active form. Since approximately half of serum calcium is bound to albumin, the serum calcium level may need to be adjusted for alterations in the albumin level. For every 1 g/dL decrease in serum albumin, “true” serum calcium may be estimated by adding 0.8 mg/dL.²

Alternatively, ionized calcium levels are widely available.

Parathyroid hormone (PTH), vitamin D, and calcitonin interact to regulate ionized calcium in a narrow range by controlling intestinal absorption, renal excretion, and skeletal distribution (Fig. 84-1). Ionized calcium levels are sensed by the calcium-sensing receptor (CaSR) on the cell surface of parathyroid cells. When ionized calcium falls, PTH is secreted. If levels are elevated, PTH secretion is suppressed. PTH in turn promotes bone resorption and increases calcium reabsorption in the kidney. As bone resorption occurs, ionized calcium and phosphorus are released into the circulation. In the kidney, PTH stimulates renal reabsorption of calcium and excretion of phosphorus. It also facilitates conversion of 25-hydroxyvitamin D to the active form, 1,25(OH)₂D, which promotes transepithelial transport of calcium and phosphorus in the intestine and the kidney.³

Calcitonin is a hormone released by the thyroid gland which plays a more subdued role in calcium homeostasis. In response to hypercalcemia, calcitonin is released and inhibits osteoclast-mediated bone resorption and renal and intestinal reabsorption of calcium.⁴

HYPOCALCEMIA

Hypocalcemia is defined as serum calcium <9 mg/dL. Major etiologies (Table 84-1) are hypoparathyroidism and vitamin D deficiency. Hypoparathyroidism leads to insufficient PTH release to stimulate release of calcium from bone and renal and intestinal preservation of calcium. It can be congenital or acquired. Magnesium is essential for PTH secretion and activation of PTH receptors. Low levels of magnesium may lead to functional hypoparathyroidism and hypocalcemia. Interestingly, high levels of magnesium (as in parenteral administration) may inhibit PTH release and also lead to hypocalcemia.³ Vitamin D deficiency or resistance can lead to hypocalcemia as well as difficulty converting vitamin D to the active form, 1,25(OH)₂D. Pseudohypoparathyroidism, characterized by resistance to the effects of PTH, may also lead to hypocalcemia, along with elevated levels of PTH and phosphorus. Additional etiologies are massive transfusion of citrated blood, phosphate enema toxicity, pancreatitis, and sepsis.