Calcium homeostasis

Calcium plays a structural role in the body as a component of bones and teeth but also as a biological trigger with roles in enzyme stimulation, neurotransmitter release, exocrine and endocrine simulation, muscle contraction, heartbeat, blood clotting.

Homeostasis aims to closely regulate the plasma concentration of Ca2+ at 2.25-2.75mmol/L and intracellular concentration of 0.1micromol/L (10^-7M). Regulation involves antagonistic hormones: parathyroid hormone (which stimulates ca2+ absorption), calcitonin (reduces osteoclastic activity and reduces reabsorption of intestinal calcium) as well as activated vitamin D3 (important in intestinal calcium absorption).

Extracellular calcium balance is regulated with hormones affecting intestinal absorption and excretion, kidney reabsorption and excretion and bone deposition and resorption. Cellular concentration is regulated by exchanging calcium with the extracellular fluid (Figure 1). body calcium is 1% in ICF, 0.1% in ECF and 99% in bone stores. Most excretion occurs through the feces but 10% is excreted in urine.

Figure 1

1,25-Dihydroxycholecalciferol/1,25 Dihydroxy Vitamin D3 plays an important role in intestinal calcium absorption (Figure 2). 7-Dehydrocholesterol is activated to Vitamin D3 (cholecalciferol) by Uv radiation through the skin. This is activated in the liver to 25-Hydroxycholecalciferol which is then activated in the kidney to 1-25-Dihydroxycholecalciferol (calcitriol). This activation is regulated by parathyroid hormone levels stimulated by low Ca2+ levels.

"To remember, consider that the precursor molecule is a cholesterol and we are talking about calcium regulation. Together these make cholecalciferol. Add on 25-OH in the liver and then 1-OH in the kidneys to result in 1,25-Dihydroxycholecalciferol."
Figure 2

Parathyroid hormone (PTH) is a polypetide hormone secreted by the parathyroid gland chief cells (Figure 3). High plasma Ca2+ has a negative feedback control of PTH production by binding the the Ca sensing receptors in the parathyroid glands. The main action of parathyroid hormone is increasing calcium reabsorption in the intestine by upregulating the production of activated vitamin D3. It can also increase reabsorption of calcium and decrease reabsorption of phosphate in the kidneys. Large or prolonged fall in plasma Ca2+ can cause PTH to stimulate osteoclasts  to resorb bone to release Ca2+ into the circulation.
Figure 3


Calcitonin is a polypeptide hormone produced in the parafollicular cells of the thyroid gland. An increase in Ca2+ has a direct influence on the parafollicular cells to increase calcitonin production. Calcitonin acts to decrease plasma Ca2+. It is a potent inhibitor of bone resorption  by inhibiting osteoclasts and preventing formation of new osteoclasts as opposed to PTH which targets the absorption/excretion of Ca2+. It has relatively weak effects on plasma Ca2+ in adults.

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