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Calcium is the key component that mediates muscle contraction; exocrine, endocrine, and neurocrine secretion; cell growth; and the transport and secretion of fluids and electrolytes. There are approximately 1300 g of calcium in a 70-kg adult, 99% of which is in the bones and teeth. The kidneys are the major organ responsible for regulating calcium between 4.5 and 5 mEq/L. Calcium is abundant in milk and milk products, is poorly absorbed by the intestine, and is excreted primarily in the feces and urine. Circulating calcium exists in three forms: bound to plasma proteins (primarily albumin) and not filtered by glomerular capillaries (40%); ionized, physiologically active, filtered at the glomerular membrane, and maintained at a concentration of 2.0 to 2.5 mEq/L (50%); and nonionized and chelated with phosphate, sulfate, and citrate (10%). Because changes in pH alter the fraction of calcium that is bound to albumin, the level of ionized calcium can change without alteration of total calcium. Most filtered calcium is reabsorbed in the proximal tubule, the thick ascending limb of the loop of Henle, and the distal tubule.
Because of calcium's importance in virtually all cellular functions, its intracellular and extracellular concentrations are tightly controlled. Energy is expended to pump intracellular calcium out of the cytosol into the sacroplasmic reticulum or ECF. As with potassium, during shock and depletion of intracellular energy, calcium accumulates within cells and has been postulated to facilitate cell death.
The concentration of serum proteins is an important determinant
of calcium ion concentration. Ionized calcium can be measured directly with the
use of calcium-specific electrodes. When ionized calcium cannot be measured, the
approximate amount of calcium bound to protein is given by the following equation:
Protein-bound calcium (%) = 0.8 × Albumin (g/L)
+ 0.2 × Globulin (g/L) + 3
Within minutes of a slight decrease in extracellular calcium concentration, the parathyroid glands release parathyroid hormone, which increases calcium reabsorption in the thick ascending limb and distal tubule, decreasing calcium excretion. Excision of the parathyroid glands eliminates parathyroid hormone secretion, which can significantly disrupt calcium homeostasis.
Calcitonin, produced in the thyroid gland, decreases renal reabsorption of calcium acutely but has little effect on chronic calcium homeostasis. Surgical removal of the thyroid gland eliminates calcitonin without changing extracellular calcium ion concentration.
Bone acts as the body's major reservoir of calcium. When the parathyroid gland releases parathyroid hormone in response to decreased calcium levels, bone reabsorption is favored, and calcium is released. Vitamin D increases absorption of calcium from the gastrointestinal tract, and its action is potentiated by parathyroid hormone.
Hypercalcemia is associated with many disease processes and has
many signs and symptoms. Mild to moderate hypercalcemia (11 to 14 mg/100 mL) often
has no symptoms, but when levels reach 15 mg/100 mL, clinical changes become more
common. Hypercalcemia produces changes primarily in the central nervous system (e.g.,
mental status changes), the gastrointestinal tract (e.g., vomiting), the kidneys
(e.g., polyuria, renal calculi, oliguric renal failure), and the heart (e.g., cardiac
conduction disturbances). Today, hypercalcemia is most commonly diagnosed in asymptomatic
patients, whereas clinical features previously were the earliest manifestations.
Potential causes of hypercalcemia include thiazide diuretic therapy, malignancy,
or parathyroid hormone adenoma. Treatment
Causes | Mechanisms |
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Parathyroid related | Primary hyperparathyroidism, including solitary adenomas and multiple endocrine neoplasias; lithium therapy; familial hypocalciuric hypercalcemia |
Vitamin D related | Vitamin D intoxication; idiopathic hypercalcemia of infancy; increase in 1,25 (OH)2 D; sarcoidosis and other granulomatous diseases |
Associated with high bone turnover | Hyperthyroidism, immobilization, thiazides, vitamin A intoxication |
Malignancy related, including associated with renal failure | Solid tumors with metastasis, solid tumors with humoral mediators of hypercalcemia, and hematologic malignancies, severe secondary hyperparathyroidism, aluminum intoxication, milk-alkali syndrome |
Adapted from Potts JT: Diseases of the parathyroid gland and other hyper- and hypocalcemic disorders. In Isselbacher KJ, Braunwald E, Wilson JD, et al (eds): Harrison's Principles of Internal Medicine, 13th ed. New York, McGraw-Hill, 1995, p 2151. |
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