Endocrine Control of Calcium and Phosphate Homeostasis
Professor R. Bowen, Dept of Biomedical Science, Colorado State University, USA.
Hypocalcemia refers to low blood calcium concentration. Clinical signs of this disorder reflect increased neuromuscular excitability and include muscle spasms, tetany and cardiac dysfunction.
Hypercalcemia indicates a concentration of blood calcium higher than normal. The normal concentration of calcium and phosphate in blood and extracellular fluid is near the saturation point; elevations can lead to diffuse precipitation of calcium phosphate in tissues, leading to widespread organ dysfunction and damage.
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:
Intracellular calcium: A large majority of calcium within cells is sequestered in mitochondria and endoplasmic reticulum. Intracellular free calcium concentrations fluctuate greatly, from roughly 100 nM to greater than 1 uM, due to release from cellular stores or influx from extracellular fluid. These fluctuations are integral to calcium's role in intracellular signaling, enzyme activation and muscle contractions.
Calcium in blood and extracellular fluid: Roughly half of the calcium in blood is bound to proteins. The concentration of ionized calcium in this compartment is normally almost invariant at approximately 1 mM, or 10,000 times the basal concentration of free calcium within cells. Also, the concentration of phosphorus in blood is essentially identical to that of calcium.
Bone calcium: A vast majority of body calcium is in bone. Within bone, 99% of the calcium is tied up in the mineral phase, but the remaining 1% is in a pool that can rapidly exchange with extracellular 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.
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.
From Hypertexts for Biomedical Sciences, Endocrine Sysytem, Thyroid and Parathyroid Glands
Reprinted here by permission of Prof R Bowen, March 2007