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Calcium Homeostasis Notes

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Calcium Homeostasis The extracellular calcium concentration is regulated by three hormones that act on calcium metabolism in bone tissue, digestive tract and kidneys. These are parathyroid hormone (PTH), calcitriol (1,25dihydroxyvitamin D) and calcitonin. 99% of calcium in the body is stored in the bone as extracellular matrix. The concentration of calcium in the ECF has an impact on many bodily activities. Calcium is regulated through a balance between intestinal absorption and renal excretion of calcium, and bone uptake and release.

1. Calcitriol Vitamin D3 or cholecalciferol is produced in the skin by conversion of 7-dehydrocholesterol via UV light. Vitamin D3 is mostly bound to vitamin D-binding globulin in the blood. It is transported to the liver where it is hydroxylated. It is then hydroxylated further in the kidneys to form calcitriol. Calcitriol binds to intracellular receptors in cells that transport calcium, such as epithelial cells in the intestine, kidneys, udder and shell gland, as well as cells in the muscle, bone and endocrine glands. The hormone receptor complex induces the formation of calcium binding proteins. The rate of calcium transport is directly proportional to the quantity of these proteins. Therefore as they increase, so does calcium uptake from the gut. Many signals regulate the renal formation of calcitriol. The most important stimulator is parathyroid hormone (PTH). Calcitriol production is also inhibited by hypercalcemia and hyperphosphatemia.

2. PTH Parathyroid hormone is produced by the chief cells in the parathyroid glands. Its overall effect is to increase the ECF concentration of calcium and prevent hypocalcemia. Parathyroid secretion is regulated by negative feedback. PTH secretion increases in response to a decline in ECF calcium concentration and decreases in response to a rise. Information of calcium ECF concentration is conveyed to the parathyroid glands via calcium receptors in the cell membrane. The receptors are coupled to a G protein that controls the exocytosis of PTH-containing vesicles. Binding of PTH to receptors in target cells increases the intracellular cAMP concentration. This effects certain enzymes and transport mechanisms, increasing reabsorption of bone tissue, renal reabsorption of calcium and formation of calcitriol. The effect of PTH on calcium mobilisation from bone has a rapid and a slow phase. The rapid phase results from activation of already existing bone cells, particularly osteocytes and also osteoblasts. The slow phase results from proliferation of osteoclasts, followed by increased osteoclastic reabsorption of bone. The effect of PTH on osteoclasts is regulated via paracrine mediators produced by neighbouring osteocytes and osteoblasts.

3. Calcitonin

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