submitted by Dr. Gary Farr Last Updated June, 30, 2003
Page: 1
What is it?
The level of calcium in the blood is closely regulated, and wide fluctuations in either direction can be life-threatening. Calcium is a key element in the human body. Not only does it serve as the major constituent for bone, but it is also essential for the normal functioning of all body cells, as it is a mediator for many cell functions. For example, without calcium, blood will not clot. Many of these actions also require adequate supplies of magnesium and phosphorus. A healthy body needs a regular, continuous supply of these elements: about a gram each day for calcium and phosphorus and about one-third as much for magnesium.
Almost all the calcium contained in the body is deposited in bone (about 1.3 kilograms in the normal adult). While this mass provides skeletal support and serves as a reserve from which calcium may be mobilized, it is the remaining 1 percent, dissolved in body fluids, whose concentration is so carefully monitored. In the plasma, calcium exists largely as a dissociated ion (Ca2+) loosely bound to plasma proteins with a small proportion bound more tightly to phosphate and citrate. To insure that calcium levels and distribution are maintained within narrow limits, parathyroid hormone (PTH), calcitonin, and the calciferols (the active metabolites of vitamin D) serve regulatory functions.
The parathyroid glands, usually four in number, are small structures adhering to or even imbedded in the substance of the thyroid gland. It is not surprising, therefore, that they were recognized as distinct endocrine organs rather late in the history of endocrinology, first described by a Swedish anatomist, Ivar Sandström, in 1880. At the beginning of the 20th century, symptoms due to parathyroid deficiency were attributed to the absence of the thyroid since the surgical removal of one was frequently accompanied by the inadvertent removal of the others. In 1909 an American pathologist, William G. MacCallum, recognized that parathyroid deficiency could be mitigated by the injection of calcium salts, and not until 1925 was an active parathyroid extract prepared by a Canadian biochemist, James B. Collip. In 1925 an Austrian surgeon, Felix Mandl, was the first to remove a parathyroid tumour from a patient, and thereafter this and related subjects were extensively explored by the American clinical endocrinologist Fuller Albright.
The parathyroids arise in the embryo from the third and fourth pairs of branchial pouches, bilateral grooves resembling gill slits in the neck of the embryo and reminders of man's evolutionary debt to fishes.
The parathyroids produce only one major hormone, parathyroid hormone (PTH), also called parathormone. Under the microscope the PTH-producing cells, the chief cells, occur in sheets interspersed with areas of fatty tissue. Occasionally the cells are arranged in follicles, similar to but smaller than those present in the thyroid gland. In common with other endocrine glands, the parathyroids synthesize a large prohormone, which is inactive. At the time of secretion the prohormone is split into an inactive fragment and PTH (a polypeptide containing 84 amino acids).
In contrast to the elaborate mechanisms controlling the secretion of other endocrine glands, the major determinant of PTH secretion is the level of ionized calcium in the serum. Should the serum calcium level rise, PTH secretion is inhibited. Conversely, should it fall, PTH levels rise. Magnesium controls PTH secretion in a similar fashion.
The actions of PTH are multiple but they are all geared toward raising the level of ionized calcium in the plasma. Parathormone mobilizes calcium from bone by stimulating the activity of large, bone-dissolving cells called osteoclasts. It acts on the kidney to enhance the reabsorption of calcium by kidney tubules so that excretion of calcium in the urine is reduced. Parathyroid hormone acting in concert with vitamin D metabolites also enhances the absorption of ingested calcium from the bowel, and there is evidence that it provokes the transfer of some calcium from the milk in the breast of a lactating woman into her blood. On the other hand, PTH is a powerful inhibitor of renal tubular reabsorption of phosphate. Finally, an ancillary action of PTH is to assist in the regulation of body acidity by blocking tubular reabsorption of bicarbonate.
Calcitonin was not recognized as a specific hormone until 1962. Calcitonin is a polypeptide containing 32 amino acids. It is synthesized and secreted from cells, termed parafollicular, or C, cells, which lie between the follicles of the thyroid gland. These cells do not have the same embryological origin as do the thyroid follicular cells; they migrate into the substance of the thyroid from a fetal structure called a branchial pouch. Human calcitonin differs considerably from the calcitonin of other species, and physicians take advantage of these differences when they administer salmon calcitonin, which provides a longer lasting, more potent action than does human calcitonin.
The major action of calcitonin is to lower the level of calcium in the blood by sharply inhibiting the ongoing dissolution of calcium from bone. Not unexpectedly, calcitonin secretion is stimulated whenever serum calcium levels rise above the normal range so that, between them, calcitonin and PTH effectively maintain steady calcemia in a normal individual.
Unlike calcitonin, the awareness of vitamin D is relatively ancient. Vitamin D deficiency was first described more than 300 years ago as rickets, but it was not until 1971 that the chemical transformations that make vitamin D biologically active were described. The term vitamin D refers to a family of compounds that are derived from cholesterol. There are two major forms of vitamin D: vitamin D3, found in animal tissues and often referred to as cholecalciferol, and vitamin D2, found in plants and now better known as ergocalciferol. Both of these compounds are inactive precursors of potent metabolites; they fall, therefore, into the category of prohormones. This is true not only for the cholecalciferol found in animal tissues but also for that which is generated in human skin following exposure to ultraviolet light. These precursors are modified during their passage through the liver to a sterol called 25-hydroxycholecalciferol, and then further modifications, modulated by the serum PTH level, occur in the kidney. One of these products, 1,25-dihydroxycholecalciferol (calcitriol), is the most potent derivative of vitamin D. The other, 24,25-dihydroxycholecalciferol, has actions that are not clearly defined at present.
Persons with a vitamin D deficiency suffer from rickets, characterized by soft, poorly calcified bone, along with poor absorption of calcium. Calcitriol or any of its precursors promotes a dramatic increase in the absorption of calcium by the intestine and a prompt repair of the diseased bone. It is generally agreed that the improvement in the bone results from the alleviation of the calcium deficiency; calcium is resorbed, but bone synthesis is not enhanced.
Nutritional Support for the Parathyroid Gland
The following supplements are commonly used in conditions involving calcium metabolism:
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