Parathyroid hormone phosphate levels

Although it is being found that vitamin D metaboUtes play a role ia many different biological functions, metaboHsm primarily occurs to maintain the calcium homeostasis of the body. When calcium semm levels fall below the normal range, 1 a,25-dihydroxy-vitainin is made when calcium levels are at or above this level, 24,25-dihydroxycholecalciferol is made, and 1 a-hydroxylase activity is discontiaued. The calcium homeostasis mechanism iavolves a hypocalcemic stimulus, which iaduces the secretion of parathyroid hormone. This causes phosphate diuresis ia the kidney, which stimulates the 1 a-hydroxylase activity and causes the hydroxylation of 25-hydroxy-vitamin D to 1 a,25-dihydroxycholecalciferol. Parathyroid hormone and 1,25-dihydroxycholecalciferol act at the bone site cooperatively to stimulate calcium mobilization from the bone (see Hormones). Calcium blood levels are also iafluenced by the effects of the metaboUte on intestinal absorption and renal resorption. 

Check parathyroid hormone (PTH), vitamin D and precursors, magnesium, and phosphate levels ° Pharmacological causes of decreased ionized calcium may include excess infusions of citrate, EDTA, lactate, fluoride poisoning, foscarnet, cinacalcet, bisphosphates, or unrelated increase in serum phosphate or decrease in serum magnesium levels... 

High phosphate diets cause decreased Ca absorption, secondary hyperparathyroidism, accelerated bone resorption and soft tissue calcification in some animals, but not in normal humans. Although phosphates may decrease Ca absorption in man at very high (> 2000 mg/day) Ca intakes, they do not do so at more moderate Ca levels and enhance Ca absorption at very low levels (< 500 mg/day). Phosphates increase renal tubular reabsorption and net retention of Ca. At low Ca intakes, phosphates stimulate parathyroid hormone (PTH) secretion without causing net bone resorption. 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Enzyme induction properties Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D. Rifampin and isoniazid have been reported to alter vitamin D metabolism. In some cases, reduced levels of circulating 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D have been accompanied by reduced serum calcium and phosphate, and elevated parathyroid hormone. 

Calcitonin is a polypeptide hormone which (along with parathyroid hormone and the vitamin D derivative, 1,25-dihydroxycholecalciferol) plays a central role in regulating serum ionized calcium (Ca +) and inorganic phosphate (P,) levels. The adult human body contains up to 2 kg of calcium, of which 98% is present in the skeleton (i.e. bone). Up to 85% of the 1kg of phosphorus present in the body is also found in the skeleton (the so-called mineral fraction of bone is largely composed of Ca3 (P04)2 which acts as a body reservoir for both calcium and phosphorus). Calcium concentrations in human serum approximate to O.lmg/ml and are regulated very tightly (serum phosphate levels are more variable). 

Parathyroid hormone is a single-chain polypeptide of 84 amino acids which is produced in the parathyroid glands. It increases serum calcium and decreases serum phosphate. In bone it promotes resorption of calcium. It indirectly increases osteoclastic activity by promoting the action of osteoblasts. It has been shown that in low doses PTH may even increase bone formation without stimulating bone resorption. In the kidney PTH increases resorption of calcium and it increases excretion of phosphate. An other important activity in the kidney is the enhanced synthesis of 1,25-dihydroxyvitamin D. An increased serum calcium level inhibits PTH secretion and increased serum phosphate decreases free serum calcium and thus stimulates PTH secretion. 

Osteomalacia is the condition in which bone becomes demineralised due to deficiency of vitamin D. In this condition parathyroid hormone (PTH) acts on the bone to maintain serum calcium, resulting in demineralisation. Serum calcium is usually normal or slightly low alkaline phosphatase levels are high, reflecting excessive osteoblast activity, and serum phosphate falls as an effect of PTH on the kidney. The same condition in children results in defects in long bone formation, and is termed rickets. 

Mechanism of Action An antibiotic that forms complexes with DNA, inhibiting DNA-directed RNA synthesis. May inhibit parathyroid hormone effect on osteoclasts and inhibit bone resorption. TherapeuticEffect Lowers serum calcium and phosphate levels. Blocks hypercalcemic action of vitamin Dand action of parathyroid hormone. Decreases serum calcium. 

Regulation of 25-hydroxycholecalciferol 1-hydroxylase 1,25-diOH D3 is the most potent vitamin D metabolite. Its formation is tightly i regulated by the level of plasma phosphate and calcium ions (Figure 28.24). 25-Hydroxycholecalciferol1 -hydroxylase activity is I increased directly by low plasma phosphate or indirectly by bw I plasma calcium, which triggers the release of parathyroid hormone I... 

The more classical Itinehoii of parathyroid hormone is concerned with its control of the maintenance of constant circulating calcium levels. Its action is on 11) Ihe kidney, where it increases the phosphate in the urine. (2) the skeletal system, where it causes calcium resorplion from bone, and t3l the digestive system, where it accelerates (stimulates) calcium absorption into the hitskI The hormone and gland exhibit characteristics of feedback control when the concentration of calcium tons in the blood falls, the secretion of the hormone increases, and when their concentration rises, the secretion of hormone decreases... 

The major location of calcium in the body is in the skeleton, which contains more than 90% of the body calcium as phosphate and carbonate. Bone resorption and formation keeps this calcium in dynamic equilibrium with ionized and complexed calcium in blood, cellular fluids and membranes. Homeostasis is mainly regulated by the parathyroid hormone and vitamin D which lead to increased blood calcium levels, and by a thyroid hormone, calcitonin, which controls the plasma calcium concentration J5 Increasing the concentration of calcitonin decreases the blood calcium level, hence injections of calcitonin are used to treat severe hyperalcaemia arising from hyperparathyroidism, vitamin D intoxication or the injection of too high a level of parathyroid extract. High levels of calcitonin also decrease resorption of calcium from bone. Hypocalcaemia stimulates parathyroid activity, leading to increased release of calcium from bone, reduction in urinary excretion of calcium and increased absorption of calcium from the intestine. Urinary excretion of phosphate is enhanced. 

Brown, EM, Fuleihan, Ge-H, Chen, CJ and Kifor, O, 1990, A comparison of the effects of divalent and trivalent cations on parathyroid hormone release, 3, 5 -cyclic-adenosine monophosphate accumulation, and the levels of inositol phosphates in bovine parathyroid cells, Endocrinology 127 1064-1071... 

Know the effects of parathyroid hormone, calcitonin, and vitamin D in controlling calcium and phosphate metabolism. Know what controls the levels of such hormones in the bloodstream. 

Calcitonin is a 32-amino-acid polypeptide hormone that was hrst purihed in 1962 by Copp and Cheney (121). It was originally thought as a product from parathyroid glands, but later it was discovered to be made by the C cells of the thyroid gland. Calcitonin participates in calcium and phosphorus metabolism, lowers plasma calcium and phosphate levels, and it has been used as a drug for bone and mineral disorders for a long time. 

Calcium is essential for the normal growth and development of the body, especially (in the form of calcium phosphate) of the bones and teeth. Its level in the blood is regulated by the opposing actions of the thyroid hormone calcitonin, and the parathyroid hormone parathormone. Its uptake from food is enhanced by vitamin D (calciferol). Forms of calcium used therapeutically include the folinic acid supplement calcium foiinate, and the mineral supplements calcium bicarbonate, calcium carbonate, calcium gluconate and calcium lactate. 

PTH Parathyroid hormone an 84-amino acid polypeptide hormone that is synthesized in the parathyroid gland and is secreted in response to low blood Ca levels. PTH acts to increase the Ca + concentration in the blood by stimulating osteoclast formation and activity, thus releasing bone calcium and phosphate into the blood. 

A. Increased levels of blood phosphate ion interact with sensors on the membrane of parathyroid cells to stimulate parathyroid hormone... 

B. Hyperparathyroidism is the likely cause of all of the patient s symptoms. Increased parathyroid hormone leads to bone demineralization, increased calcium uptake from the intestine, increased blood levels of calcium, decreased calcium ion excretion by the kidney, and increased phosphate excretion in the urine. Increased blood calcium levels caused renal stones, while bone demineralization progressed to osteopenia. The patient s intake of calcium and vitamin D are not excessive. Calcitonin acts to decrease bone demineralization. Muscle weakness and depression reflect the widespread role of calcium ion in many physiologic processes. 

C. The major action of vitamin D is to increase absorption of calcium from the small intestine. Deficiency of the vitamin leads to low blood calcium levels, stimulation of parathyroid hormone secretion, and acting synergistically, promotion of bone demineralization. Renal excretion of calcium is decreased by hypocalcemia but elevated parathyroid hormone levels promote renal excretion of phosphate, to prevent excessive accumulation of this product of bone demineralization. Although lack of exercise decreases bone density, it does not lead to rickets if vitamin D is sufficient. 

The capacity of the tubules to reabsorb or secrete a substance is subject to several variables. Thus, the expansion of extracellular fluid volume inhibits the reabsorption of sodium, bicarbonate, and phosphate and depresses the secretion of PAH. The tubular reabsorption of phosphate is inhibited by increased circulating levels of parathyroid hormone. The reabsorption of phosphate and bicarbonate by the tubules is directly related to the glomerular filtration rate. The reabsorption of bicarbonate by the tubule is also directly related to the pC02 level. 

In addition to an increase in serum urea and creatinine levels, uric acid and inorganic phosphate levels also increase in chronic renal failure. The increase in serum inorganic phosphate leads to deposition of calcium phosphate in bones, causing hypocalcemia. In the early stages of chronic renal failure, calcium levels are restored by the stimulation of parathyroid hormone. However, as the renal disease progresses, the ability of the kidney to hydroxylate vitamin D and thus convert it to the active form decreases, thereby affecting the uptake of calcium by the gut and thus perpetuating hypocalcemia. Serum alkaline phosphatase levels increase due to disordered bone metabolism. Loss of bicarbonate is seen in some patients with increased parathyroid hormone activity. 

Features of lithium-induced hyperparathyroidism include a) a low urinary calcium excretion and the absence of nephrolithiasis b) normal urinary cyclic adenosine monophosphate excretion and c) normal plasma inorganic phosphate [30]. In lithium-induced hypercalcemia, a higher frequency of conduction defects has been noted [42]. Lithium also inhibits parathyroid hormone-mediated renal reabsorption of Ca and Mg and blunts parathyroid hormone-mediated phos-phaturia [43]. Lithium interferes with the formation of renal cyclic adenosine monophosphate, which is regulated by parathyroid hormone. Levels of minary cy-... 

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