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 1,25dihydroxyvitamin 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