Endocrine System > Thyroid and Parathyroid Glands

Endocrine Control of Calcium and Phosphate Homeostasis

It would be very difficult to name a physiologic process that does not depend, in one way or another, on calcium. It is critical to maintain blood calcium concentrations within a tight normal range. Deviations above or below the normal range frequently lead to serious disease.

Preventing hypercalcemia and hypocalcemia is largely the result of robust endocrine control systems.

Body Distribution of Calcium and Phosphate

There are three major pools of calcium in the body:

As with calcium, the majority of body phosphate (approximately 85%) is present in the mineral phase of bone. The remainder of body phosphate is present in a variety of inorganic and organic compounds distributed within both intracellular and extracellular compartments. Normal blood concentrations of phosphate are very similar to calcium.

Fluxes of Calcium and Phosphate

Maintaining constant concentrations of calcium in blood requires frequent adjustments, which can be described as fluxes of calcium between blood and other body compartments. Three organs participate in supplying calcium to blood and removing it from blood when necessary:

  • The small intestine is the site where dietary calcium is absorbed. Importantly, efficient absorption of calcium in the small intestine is dependent on expression of a calcium-binding protein in epithelial cells.
  • Bone serves as a vast reservoir of calcium. Stimulating net resorption of bone mineral releases calcium and phosphate into blood, and suppressing this effect allows calcium to be deposited in bone.
  • The kidney is critcally important in calcium homeostasis. Under normal blood calcium concentrations, almost all of the calcium that enters glomerular filtrate is reabsorbed from the tubular system back into blood, which preserves blood calcium levels. If tubular reabsorption of calcium decreases, calcium is lost by excretion into urine.

Hormonal Control Systems

Maintaining normal blood calcium and phosphorus concentrations is managed through the concerted action of three hormones that control fluxes of calcium in and out of blood and extracellular fluid:

Parathyroid hormone serves to increase blood concentrations of calcium. Mechanistically, parathyroid hormone preserves blood calcium by several major effects:

Vitamin D acts also to increase blood concentrations of calcium. It is generated through the activity of parathyroid hormone within the kidney. Far and away the most important effect of vitamin D is to facilitate absorption of calcium from the small intestine. In concert with parathyroid hormone, vitamin D also enhances fluxes of calcium out of bone.

Calcitonin is a hormone that functions to reduce blood calcium levels. It is secreted in response to hypercalcemia and has at least two effects:

Although calcitonin has significant calcium-lowing effects in some species, it appears to have a minimal influence on blood calcium levels in humans.

A useful way of looking at how hormones affect tissues to preserve calcium homeostasis is to examine the effects of calcium deprivation and calcium loading. The following table summarizes body responses to conditions that would otherwise lead to serious imbalances in calcium and phosphate levels in blood.

Calcium Deprivation Calcium Loading
Parathyroid hormone Secretion stimulated Secretion inhibited
Vitamin D Production stimulated by increased parathyroid hormone secretion Synthesis suppressed due to low parathyroid hormone secretion
Calcitonin Very low level secretion Secretion stimulated by high blood calcium
Intestinal absorption of calcium Enhanced due to activity of vitamin D on intestinal epithelial cells Low basal uptake
Release of calcium and phosphate from bone Stimulated by increased parathyroid hormone and vitamin D Decreased due to low parathyroid hormone and vitamin D
Renal excretion of calcium Decreased due to enhanced tubular reabsorption stimulated by elevated parathyroid hormone and vitamin D; hypocalcemia also activates calcium sensors in loop of Henle to directly facilitate calcium reabsorption Elevated due to decreased parathyroid hormone-stimulated reabsorption.
Renal excretion of phosphate Strongly stimulated by parathyroid hormone; this phosphaturic activity prevents adverse effects of elevated phosphate from bone resorption Decreased due to hypoparathyroidism
General Response Typically see near normal serum concentrations of calcium and phosphate due to compensatory mechanisms. Long term deprivation leads to bone thining (osteopenia). Low intestinal absorption and enhanced renal excretion guard against development of hypercalcemia.

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