Disorders of Calcium Balance
Although 98% of total body calcium is in bone, maintenance of a normal extracellular calcium con-centration is critical to homeostasis. Calcium ions are involved in nearly all essential biological func-tions, including muscle contraction, the release of neurotransmitters and hormones, blood coagula-tion, and bone metabolism, and abnormalities in calcium balance can result in profound physiologi-cal derangements.
NORMAL CALCIUM BALANCE
Calcium intake in adults averages 600–800 mg/d. Intestinal absorption of calcium occurs primar-ily in the proximal small bowel but is variable. Calcium is also secreted into the intestinal tract; moreover, this secretion appears to be constant and independent of absorption. Up to 80% of the daily calcium intake is normally lost in feces.
The kidneys are responsible for most cal-cium excretion. Renal calcium excretion averages 100 mg/d but may vary from as low as 50 mg/d to more than 300 mg/d. Normally, 98% of the filterable calcium is reabsorbed. Calcium reabsorption paral-lels that of sodium in the proximal renal tubules and the ascending loop of Henle. In the distal tubules, however, calcium reabsorption is dependent on parathyroid hormone (PTH) secretion, whereas sodium reabsorption is dependent on aldosterone secretion. Increased PTH levels enhance distal calcium reabsorption and thereby decrease urinary calcium excretion.
The normal plasma calcium concentration is 8.5–10.5 mg/dL (2.1–2.6 mmol/L). Approximately 50% is in the free ionized form, 40% is protein bound (mainly to albumin), and 10% is complexed with anions such as citrate and amino acids. The free ionized calcium concentration ([Ca 2+]) is physiologically most important. Plasma [Ca2+] is normally 4.75–5.3 mg/dL (2.38–2.66 mEq/L or 1.19–1.33 mmol/L). Changes in plasma albumin concentration affect total but not ionized calcium concentrations: for each increase or decrease of 1 g/dL in albumin, the total plasma calcium con-centration increases or decreases approximately 0.8–1.0 mg/dL, respectively.Changes in plasma pH directly affect the degree of protein binding and thus ionized calcium con-centration. Ionized calcium increases approximately0.16 mg/dL for each decrease of 0.1 unit in plasma pH and decreases by the same amount for each 0.1 unit increase in pH.
Calcium normally enters ECF by either absorp-tion from the intestinal tract or resorption of bone; only 0.5–1% of calcium in bone is exchangeable with ECF. In contrast, calcium normally leaves the extracellular compartment by (1) deposition into bone, (2) urinary excretion, (3) secretion into the intestinal tract, and (4) sweat formation. Extracel-lular [Ca2+] is closely regulated by three hormones: parathyroid hormone (parathormone, PTH), vita-min D, and calcitonin. These hormones act primar-ily on bone, the distal renal tubules, and the small bowel.
PTHis the most important regulator of plasma[Ca2+]. Decreases in plasma [Ca2+] stimulate PTH secretion, while increases in plasma [Ca2+] inhibit PTH secretion. The calcemic effect of PTH is due tomobilization of calcium from bone, (2) enhance-ment of calcium reabsorption in the distal renal tubules, and (3) an indirect increase in intestinal absorption of calcium via acceleration of 1,25-dihy-droxycholecalciferol synthesis in the kidneys .
Vitamin D exists in several forms in the body,but 1,25-dihydroxycholecalciferol has the most important biological activity. It is the product of the metabolic conversion of (primarily endogenous) cholecalciferol, first by the liver to 25-cholecalcif-erol and then by the kidneys to 1,25-dihydroxycho-lecalciferol. The latter transformation is enhanced by secretion of PTH as well as hypophosphatemia. Vitamin D augments intestinal absorption of cal-cium, facilitates the action of PTH on bone, and appears to augment renal reabsorption of calcium in the distal tubules.
Calcitonin is a polypeptide hormone that issecreted by parafollicular cells in the thyroid gland. Its secretion is stimulated by hypercalcemia and inhibited by hypocalcemia. Calcitonin inhibits bone reabsorption and increases urinary calcium excretion.
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