Calcium is the most abundant mineral in the body. The total body calcium is between 1.0 and 1.5 kg or 10 and 20 g/kg of body weight in an average-sized adult. Calcium, also the most abundant cation in the body, is 99 percent bound in bone as phosphate and carbonate (mineral apatite), with the remainder in the ECF compartment. The normal daily intake of calcium is 800 to 3000 mg, one-third of which is absorbed primarily in the small bowel via both active (vitamin D-dependent) and passive (concentration-dependent) absorption. Most of the calcium we ingest is found in milk and milk products. Most of this calcium is excreted through the gastrointestinal tract via the stool, with 200 mg or less in the urine.
The gradient between the intravascular and extravascular compartments is highly regulated to maintain a ratio of 10,000:1. The measured serum concentration of calcium ranges from 8.5 to 10.5 mg/dL and is maintained by the function of parathyroid hormone, vitamin D metabolites (1a,25-dihydroxyvitamin D 3, or calcitriol), and calcitonin.
Parathormone (parathyroid hormone, or PTH) is secreted by the parathyroid gland in response to low ionized calcium or magnesium levels. It raises serum calcium primarily by stimulating osteoclasts to increase bone resorption. It secondarily increases serum calcium by both indirect action in the kidney (increases calcium resorption and phosphorus excretion) and in conjunction with calcitriol to increase intestinal absorption. Calcitonin is influenced by elevations in serum calcium, epinephrine, glucagon, and gastrin. Its primary effect is to inhibit the activity of osteoclasts, with a limited secondary effect to potentiate calcium loss through the kidney. Vitamin D can be produced nonenzymatically by ultraviolet irradiation of skin or can be absorbed directly from the gastrointestinal tract. It is hydroxylated first in the liver and again in the kidney to create its more potent form. Upregulation of this process occurs with hypocalcemia or hypophosphatemia.
The intravascular calcium exists as 50 percent bound to plasma proteins, i.e., albumin (4.0 to 4.5 mg/dL), 45 percent free active ions (4.2 to 4.8 mg/dL), and 5 percent nonionized (bound to other substances in plasma and interstitial fluids). A laboratory value reported in meq/L is equal to half the amount in mg/dL; therefore, a value of 4.2 mg/dL = 2.1 meq/L (= 1.05 mosm/L).
Changes in hydrogen concentration result in changes to the ionized calcium concentration. This occurs because calcium binds to the protein in place of hydrogen ions. For example, hyperventilation leads to respiratory alkalosis and an attendant decrease in [H +]. The decreased [H+] causes an increase in protein-bound calcium and a decrease in serum ionized calcium (relative hypocalcemia).
It is the ionized fraction that is physiologic activity. Signs and symptoms of hypocalcemia usually occur when the ionized fraction drops below 3.0 mg/dL, while those associated with hypercalcemia occur with total serum calcium greater than 11 mg/dL.
Various factors affect serum calcium:
1. Serum protein, of which albumin is the major component. On average, 0.8 mg of calcium binds to 1 g of protein. Therefore, total serum [Ca 2+] = ionized [Ca2+] + (0.8 * total protein). A 1-g decrease in albumin results in a 0.8 mg/dL decrease in calcium with no change in ionized fraction.
2. Alkalosis: decrease in ionized fraction with no change in the total serum calcium. Each 0.1 rise in pH lowers ionized [Ca 2+] by about 3 to 8 percent.
3. Acidosis: increase in ionized fraction with no change in the total serum calcium.
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