Phosphate soft tissue calcification

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. 

Patients with advanced renal insufficiency (Ccr less than 30 mL/min) exhibit phosphate retention and some degree of hyperphosphatemia. The retention of phosphate plays a role in causing secondary hyperparathyroidism associated with osteodystrophy and soft-tissue calcification. Calcium acetate, when taken with meals, combines with dietary phosphate to form insoluble calcium phosphate, which is excreted in the feces. 

It appears that increased plasma phosphate concentrations are not directly toxic (Sutters et al 1996). Hypocalcemia and metastatic soft-tissue calcification caused by hyperphosphatemia result from the calcium/phosphate product exceeding that required for precipitation of calcium phosphate in the tissues (Macintire 1997, Sutters et al 1996). 

Parathyroid hormone (PTH) Primary hyperparathyroidism causes hypercalcemia, hypophosphatemia, and increased urinary cAMP hypoparathyroidism causes hypocalcemia and hyperphosphatemia, often with soft-tissue calcification and tetany and convulsions. Binds to cell-surface receptors and activates adenylate cyclase increases bone mineralization and activity of renal lot-hydroxylase in kidney, reabsorption of Ca " " increases and reabsorption of phosphate decreases. 

The major effects of hyperphosphatemia are related to the development of hypocalcemia (caused by phosphate inhibition of renal la-hydroxylase) and its related consequences, as well as vascular and organ damage resulting from the deposition of calcium-phosphate crystals. Extravascular calcification can result in band keratopathy, red eye, pruritus, and periarticular calcification, especially in renal failure patients (see Chap. 44). In addition, soft-tissue calcifications in the conjunctiva, skin, heart, cornea, lung, gastric mucosa, and kidney have been observed, primarily in chronic renal failure patients." Hyperphosphatemia associated with chronic renal disease may result in renal osteodystrophy because of overproduction of parathyroid hormone. This condition is discussed in detail in Chap. 44. 

Parenteral phosphorus supplementation is associated with risks of hyperphosphatemia, metastatic soft tissue deposition of calcium-phosphate product, hypomagnesemia, hypocalcemia, and hyperkalemia or hypernatremia (caused by intravenous phosphorus salt) (Table 49-9). Inappropriate administration of large doses of parenteral phosphorus over relatively short time periods has resulted in symptomatic hypocalcemia and soft-tissue calcification. The rate of infusion and choice of initial dosage should therefore be based on severity of hypophosphatemia, presence of symptoms, and coexistent medical conditions. Patients should be closely monitored with frequent (every 6 hours) serum phosphorus determinations for 48 to 72 hours after starting intravenous therapy. It may be necessary to continue administration of intravenous phosphorus for several days in some patients, while other patients may be able to tolerate an... 

Jowsey J, Balasubramaniam P. 1972. Effect of phosphate supplements on soft-tissue calcification and bone turnover. Clin Sci 42 289-299. 

Intoxication with vitamin D causes weakness, nausea, loss of appetite, headache, abdominal pains, cramps, and diarrhea. More seriously, it also causes hypercalcemia, with plasma concentrations of calcium between 2.75 to 4.5 mmol per L, compared with the normal range of 2.2 to 2.5 mmol per L. At plasma concentrations of calcium above 3.75 mmol per L, vascular smooth muscle may contract abnormally, leading to hypertension and hypertensive encephalopathy. Hypercalciuria may also result in the precipitation of calcium phosphate in the renal tubules and hence the development of urinary calculi. Hypercalcemia can also result in calcinosis - the calcification of soft tissues, including kidneys, heart, lungs, and blood vessels. This is assumed to be the result of increased calcium uptake into tissues in response to excessive plasma concentrations of the vitamin and its metabolites. 

Hypoparathyroidism can result from decreased production of PTH or failure of target organs to respond to PTH. In rare cases, it involves the production of genetically defective PTH. PTH provokes the kidney to conserve calcium and to excrete phosphate. Thus, hypoparathyroidism results in low plasma calcium and high plasma phosphate levels. The disease may result in the calcification of soft tissues because of the high plasma phosphate level. Elevated phosphate levels result in an increased rate of precipitation of calcium and phosphate as the calcium phosphate salt. The disease is treated with oral calcium supplements and phosphate-binding antacids to minimize the absorption of dietary phosphate. 

The relationship between calcium and phosphate metabolism is very complex. The question of the ratio of calcium/phosphate in the diet may be raised when discussing diets needed to support maximal growth or when discussing pathological phenomena, such as h5q)Ocalcemia, osteoporosis, kidney stone formation, and the calcification of soft tissues. A firm groimding in one or two relationships in calcium... 

Derangements in mineral metabolism frequently lead to metastatic calcification of soft tissue. Bone-seeking radionuclides, such as "Relabeled phosphate preparations, are proving particularly useful in detecting extra-skeletal calcification in situations where roentgenographic demonstration is lacking.61... 

Vitamin D Excess (vitamin D toxicosis) causes hypercalciuria and hypercalcemia, leading to urolithiasis and soft-tissue (especially renal) calcification insufficiency causes rickets and osteoporosis. As 1, 25-(0H)2D, increases bone resorption and intestinal and renal Ca " and phosphate absorption other metabolites may have other activities, especially in bone. 

In dystrophic calcifications, the mineralisation occurs without a systemic mineral imbalance as a response to previous cell injury on the microscopic level or any soft tissue damage, including that involved in implantation of medical devices or bioprosthetic heart valves [25], Injury and cell death can cause the release of intracellular phosphate ions and fatty acids into the extracellular environment, where sparingly soluble calcium salts are precipitated in tissues. This type of calcification is particularly common in atherosclerosis and diseases associated with chronic inflammation. 

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