Introduction
Calcium and phosphorus are essential nutrients involved in many biological processes. These minerals are the most abundant elements in the body, with 99% of Ca and 80% of P stored in the skeleton as hydroxyapatite, and both play an important role in bone development and mineralization. The calcium and phosphate homeostasis is controlled by shifts of calcium and phosphate among five different compartments. These are,
1. Bone and bone fluids,
2 Extracellular fluids (ECF),
3. Intracellular pool, itself divided into several compartments,
4. Intestinal lumen; and
5. Renal tubular fluid.
The homeostasis between all these five compartments is maintained primarily by three hormones: parathyroid hormone (PTH), calcitonin (CT), and cholecalciferol (Vitamin D3). The parathyroid hormone is secreted by the parathyroid glands. Its main action is to mobilize calcium from bone and increase urinary phosphate excretion. Calcitonin is secreted primarily by cells in the thyroid gland and it inhibits bone resorption. 1,25-Dihydroxycholecal-ciferol is a steroid hormone formed from vitamin D and it increases calcium absorption from the intestine.
The three organs participating in supplying calcium to blood and removing it from the blood when necessary are small intestine, bone, and kidneys. The dietary calcium is absorbed in the small intestine. The efficient absorption of calcium in the small intestine is dependent on expression of a calcium-binding protein in epithelial cells. Bone acts as the main reservoir of calcium. Stimulating net resorption of bone mineral releases calcium and phosphate into blood, and suppressing this effect allows ……….. Content available in book……….Content available in book……….Content available in book……….Content available in book……….Content available in book……….
Calcium
The body contains approximately 1 ½ percent calcium by weight, and almost all of this is located in the skeleton. Most of the calcium is present in the skeleton, but a small amount is present in blood and extracellular fluid. This small amount of calcium plays a vital role in the function of the body, affecting enzyme activity, membrane permeability, and neuromuscular excitability. Plasma calcium is normally at a concentration of around 10 mg/dL (5 mEq/L, 2.5 mmol/L). A fall in serum calcium level may produce tetany and death, while hypercalcemia produces functional disturbances and cardiac effects. The serum calcium level depends on a balance between calcium added from intestinal absorption and bone resorption, and calcium lost from the blood by excretion in urine and feces and deposition in bone salts.
Hormones participating in calcium and phosphorus metabolism
Various hormones are involved in the homeostasis of calcium and phosphorous levels in the blood. These include para-thyroid hormone, Vitamin D and calcitonin (Figure 24.1).
Parathyroid hormone:
The parathyroid glands are four or more small glands, about the size of a grain of rice, located on the posterior surface of the thyroid gland. The primary functional cells of the parathyroid glands are the chief cells. These epithelial cells produce and secrete the parathyroid hormone (PTH). The primary function of this hormone is to maintain the body’s calcium level within a very narrow range. The normal plasma level of intact PTH is 10 to 55 pg/mL. The half-life of PTH is approximately 10 min. Parathyroid hormone regulates serum calcium through its effects on bone, kidney, and the intestine. In bone, PTH enhances the release of calcium. It reduces the reabsorption of phosphate from the proximal tubule of the kidney, which means more phosphate is excreted through the urine. In the intestine, via the kidney, PTH enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. The secretion of parathyroid hormone is regulated at multiple levels. The circulating ionized calcium acts directly on the parathyroid glands in a negative feedback fashion to regulate the secretion of PTH. In other words, when the plasma calcium level is high, PTH secretion is inhibited and the Ca2+ is deposited in the bones; whereas, when the plasma calcium level is low, PTH secretion is increased and Ca2+ is mobilized from the Content available in book……….Content available in book……….Content available in book……….Content available in book……….Content available in book……….Content available in book……….
One more protein in the body that has PTH like activity is parathyroid hormone-related protein (PTHrP). It is structura-lly different from PTH in that it has 140 amino acid residues, compared with 84 in PTH. Both PTH and PTHrP bind to the hPTH/ PTHrP receptor. However, their physiological effects are different. PTHrP has a marked effect on the growth and development of cartilage in utero.
Vitamin D and Hydroxycholecalciferols:
Vitamin D is synthesized from the conversion of the precursor 7-dehydrocholesterol in the skin to vitamin D3 by ultraviolet (UV) B sun-rays. The most accurate way to measure how much vitamin D is in your body is the 25-hydroxy vitamin D blood test. A level of 20 ng/mL to 50 ng/mL is considered adequate for healthy people. A level less than 12 ng/mL indicates vitamin D deficiency. Vitamin D hormone functions to increase serum calcium concentrations through three separate mechanisms,
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3. It increases the synthetic activity of osteoblasts and is necessary for normal calcification of the matrix. Along with this, vitamin D hormone stimulates osteoblasts to produce receptor activator nuclear factor-κB ligand (RANKL). RANKL then stimulates osteoclastogenesis and activates resting osteoclasts for bone resorption. Thus, vitamin D plays a very important role in the remodeling of the bone.
Calcitonin:
Calcitonin is a 32-amino acid linear polypeptide hormone that is produced by the parafollicular cells (commonly known as C-cells) of the thyroid gland. It is involved in regulating levels of calcium and phosphate in the blood. The action of this hormone is opposite to that of parathyroid hormone. This hormone is secreted from thyroid glands in response to a high plasma Ca2+ concentration and its expression is regulated by 1,25(OH)2D3. Receptors for calcitonin are present in bones and the kidneys. It lowers circulating calcium and phosphate levels. It also functions as an inhibitor of bone resorption, thus leading to a decreased plasma Ca2+concentration. It also increases Content available in book……….Content available in book……….Content available in book……….Content available in book……….Content available in book……….Content available in book……….Content available in book……….
It must be noted here that unlike PTH and 1,25-Dihydroxycholecalciferol, the exact physiologic role of calcitonin is uncertain. This is because, it has been observed that after thyroidectomy, bone density and plasma Ca2+ level are normal if the parathyroid glands are working normally. Furthermore, it has been shown that after thyroidectomy, only transient abnormalities of Ca2+ metabolism are observed after the infusion of the Ca2+ load. This may also be explained by secretion of calcitonin from tissues other than the thyroid. However, this hormone has a little long-term effect on the plasma Ca2+ levels.
Conclusion
In the above discussion, we studied the mechanisms by which the three hormones; PTH, vitamin D, and calcitonin regulate the calcium and phosphate levels in our body. PTH increases plasma Ca2+ by mobilizing this ion from bone, increasing Ca2+ reabsorption in the kidney and increasing the formation of 1,25-dihydroxycholecalciferol. Vitamin D (1,25-Dihydroxy-cholecalciferol) increases Ca2+ absorption from the intestine and increases Ca2+ reabsorption in the kidneys. Calcitonin inhibits bone resorption and increases the amount of Ca2+ in the urine.
Periobasics: A Textbook of Periodontics and Implantology
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