CALCIUM PHYSIOLOGY(Source: Sabiston textbook of surgery, 19th edition)

Calcium exists in extracellular plasma in a free ionized state, as well as bound to other molecules. So-called normal plasma levels of total calcium vary among laboratories, but the range of (bound and unbound) calcium is usually between 8.5 and 10.2 mg/dL (2.2 and 2.5 mmol/liter). The biologically inert bound fraction (55% of the total) binds to proteins. Changes in albumin alter total calcium levels significantly because most protein-bound calcium associates with albumin (80%). A small percentage of calcium is associated with other proteins, such as -globulins, or with nonprotein molecules, such as phosphate and citrate. Mathematical formulas correcting for disparate albumin levels (e.g., corrected calcium = 0.8-mg/dL decrease for every 1.0-mg/dL decrease in albumin; [total calcium + 0.025] [40 albumin]) are notoriously inaccurate. Consequently, ionized calcium levels are measured when required. Forty-five percent of the total calcium is biologically active and exists in the ionized form, with a normal level of 4.5 to 5.0 mg/dL. Ionized calcium levels are inversely affected by the pH of blood; a 1-unit rise in pH will decrease the ionized calcium level by 0.36 mmol/liter.12 Accordingly, patients who are hypocalcemic and hyperventilate can enhance their hypocalcemic symptoms, including perioral paresthesia, tingling in the fingers and toes, muscle cramping, and seizures. Levels of calcium are highly modulated through a delicate interplay among PTH, calcitonin, and vitamin D acting on target organs such as bone, kidney, and the gastrointestinal (GI) glands secrete PTH, an 84 amino acid protein, whenever serum calcium levels fall. PTH binds to its peripheral receptors and stimulates osteoclasts to increase bone resorption, to the kidney to increase calcium resorption and renal production of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), and to the intestine to increase absorption of calcium and phosphate. Together, these processes raise the serum calcium level. The recently cloned calcium-sensing receptors (CaSRs) in the parathyroid glands detect changes in calcium levels, which results in a negative feedback loop that decreases PTH production. Calcitonin is a 32amino acid protein secreted by the parafollicular cells of the thyroid gland in response to high calcium levels. Its actions oppose those of PTH. Calcitonin rapidly inhibits bone resorption, thereby leading to a transient decrease in serum calcium levels. Although calcitonin plays a significant homeostatic function in other species, its effects on calcium metabolism in humans is not significant when a person is exposed to chronically elevated calcitonin levels. Accordingly, patients with extensive medullary carcinoma of the thyroid who have extraordinarily high serum calcitonin levels are usually eucalcemic. Vitamin D is ingested or synthesized in precursor form, which then undergoes two hydroxylation steps before becoming biologically active. The first hydroxylation at carbon 25 occurs in the liver and the second hydroxylation at carbon 1 occurs in the kidney in response to increased PTH levels. 1,25(OH)2D3 increases calcium and phosphate resorption from the GI tract and stimulates bone resorption, which raises calcium levels. As a result, patients who are deficient in 1,25(OH)2D3 have an impaired ability to absorb calcium from their GI tract