new_n_lost
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this is one topic which has been boggling us all so i m giving a review on the PTH n its effect on Calcium n Phosphate n Vit D interaction.
PTH is a peptide containing 84 amino acids that is secreted by the parathyroid glands after cleavage from preproparathyroid hormone (115 amino acids) to proparathyroid hormone (90 amino acids) to the mature hormone.
PTH has 3 major actions.
1. The first action is to increase renal calcium resorption and phosphate excretion. In the kidney, PTH blocks reabsorption of phosphate in the proximal tubule while promoting calcium reabsorption in the ascending loop of Henle, distal tubule, and collecting tubule.
2. PTH promotes absorption of calcium from the bone in 2 ways. The rapid phase brings about a rise in serum calcium within minutes and appears to occur at the level of the osteoblasts and osteocytes. When PTH binds to receptors on these cells, the osteocytic membrane pumps calcium ions from the bone fluid into the extracellular fluid.
The slow phase of bone resorption occurs over several days and has 2 components. First, osteoclasts are activated to digest formed bone, and second, proliferation of osteoclasts occurs. Interestingly, mature osteoclasts lack PTH membrane receptors; activation and proliferation appear to be stimulated by cytokines released by activated osteoblasts and osteocytes or by differentiation of immature osteoclast precursors that possess PTH and vitamin D receptors.
3. The third major action of PTH is conversion of 25-hydroxyvitamin D to its most active metabolite, 1,25-dihydroxyvitamin D-3 [1,25-(OH)2 D3], by activation of enzyme 1-hydroxylase in the proximal tubules of the kidney.
Negative inhibition of PTH release occurs primarily by direct effect of calcium at the level of the parathyroid gland.1,25-(OH)2 D3 appears to exert a mild inhibitory effect on the parathyroid gland as well.
Phosphate:
The excess ingested phosphate is excreted by the kidneys to maintain phosphate balance. Major sites of regulation of phosphate excretion are the early proximal renal tubule and the distal convoluted tubule. In the proximal tubule, phosphate reabsorption by type 2 sodium phosphate cotransporters is regulated by dietary phosphate, PTH, and vitamin D. High dietary phosphate intake and elevated PTH levels decrease proximal renal tubule phosphate absorption, thus enhancing renal excretion.
Conversely, low dietary phosphate intake, low PTH levels, and high vitamin D levels enhance renal proximal tubule phosphate absorption. To some extent, phosphate regulates its own regulators. High phosphate concentrations in the blood down-regulate the expression of some phosphate transporters, decrease vitamin D production, and increase PTH secretion by the parathyroid gland. Distal tubule phosphate handling is less well understood. PTH increases phosphate absorption in the distal tubule, but the mechanisms by which this occurs are unknown. Renal phosphate excretion can also be increased by the administration of loop diuretics.
Vit D:
Vitamin D-3 (cholecalciferol) is formed in the skin when a cholesterol precursor, 7-dehydroxycholesterol, is exposed to ultraviolet light. Activation occurs when the substance undergoes 25-hydroxylation in the liver and 1-hydroxylation in the kidney. The primary action of 1,25-(OH)2 D3 is to promote gut absorption of calcium by stimulating formation of calcium-binding protein within the intestinal epithelial cells. Vitamin D also promotes intestinal absorption of phosphate ion, although the exact mechanism is unclear. Negatively charged phosphate ion may passively flow through the intestinal cell because of flux of the positively charged calcium ion. In bone, vitamin D may play a synergistic role with PTH in stimulating osteoclast proliferation and bone resorption.
The major function of vitamin D is to increase the efficiency of calcium absorption from the small intestine. maximum calcium absorption occurs at levels of 25-hydroxyvitamin D (25[OH]D) greater than 32 ng/mL. Vitamin D also enhances the absorption of phosphorus from the distal small bowel. Adequate calcium and phosphorus absorption from the intestine is important for proper mineralization of the bone. The second major function of vitamin D is for the maturation of osteoclasts to resorb calcium from the bones.
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