Metastatic calcification

Chronic hypercalcemia (i.e., hyperparathyroidism) is associated with metastatic calcification, nephrolithiasis, and chronic renal insufficiency. 

The heart may be enlarged with left ventricular hypertrophy, particularly in cases which have exhibited hypertension during life. Metastatic calcification of the valves and of the myocardium may be present, explaining no doubt the cardiac murmurs which may have been detected clinically in such cases. Occasionally, medullary proliferation of large arteries and, in the smaller arteries, fragmentation of the intimal elastic lamina has been reported, in one case with impregnation with calcium salts. Local calcification of the media of the middle cerebral artery has been described. 

Hypercalcaemia and hyperphosphatemia may lead to metastatic calcification. The-kidney, arteries, muscles and gastric mucosa are mainly involved. 

A fatal case of hypervitaminosis A involved a premature neonate who died after having ingested 30 000 micrograms RE/day (90 000 lU/day), that is 60 times the recommended intake of vitamin A, for 11 days. On autopsy the skeleton showed marked alterations of endochondral bone formation. There was also evidence of accelerated resorption of bone, hypercalcemia, and metastatic calcification of the skin, soft tissues, and organs (59). 

Some individuals develop hypertension in response to vitamin D, which in some of them may be directly related to hypercalcemia and which may be reversible when renal function is normalized (12). Metastatic calcification is observed in various tissues (13), but arterial calcification is the most usual. In some patients undergoing dialysis, calcification of the blood vessels has been so extensive that cannulation could not be performed (14). 

In patients with pancreatitis associated with hypercalcemia of unclear origin, vitamin D poisoning can be responsible, especially when episodes are recurrent (41). Metastatic calcification of the pancreatic ducts has also been reported (42,43). 

Vitamin D Hypertension Hypercalcemia Metastatic calcification Bone demineralization Renal calcinosis and kidney failure... 

Hypervitaminosis D apparently cannot arise from excessive exposure to sunlight but only occurs following inge.s-tion of large quantities of synthetic vitamin D for months The amount necessary has been estimated at 50,000 units or more in a person with normal parathyroid function. The mechanism may involve formation of excessive amounts of the vitamin D metabolite 25-OHD. Toxicity involves derangements of calcium metabolism, resulting in hypercalcemia and metastatic calcification of soft tissue. Most problems result from the hypercalcemia, which typically causes muscular weakness, anorexia, nausea, vomiting, and depression of the central nervous system (which can result in coma and death). In addition, deposition of calcium salts in the kidneys (nephrocalcinosis) and the tubules (nephrolithiasis)... 

Hypervitaminosis A and D have also been associated with bone abnormalities. Vitamin D can cause resorption of calcium from bone. Chronic vitamin D intoxication may result in increased mineralization on bone and metastatic calcifications including joints, periarticular, and the kidney. Excessive vitamin D intake can cause demineralization of bone resulting in multiple fractures from very slight trauma. 

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... 

J. S. Duthie, H. P. Solanki, M. Knshnamurthy, et al. Milk-alkali syndrome with metastatic calcification. American Journal of Medicine 99, 102 (1995). 

Finally, intravenous phosphate may rapidly reduce ionized calcium concentrations through the formation of insoluble calcium-phosphate salts. However, intravenous phosphate is extremely hazardous because extraskeletal precipitation of calcium-phosphate may result in metastatic calcification, hypotension, acute renal failure, or death. Therefore intravenous phosphates should be reserved for the extraordinary patient with severe hypercalcemia and concomitant hypophosphatemia. Oral phosphorus is not used chronically for the treatment of hypercalcemia because calcium-phosphate crystals may precipitate in the kidneys or other major organs when the calcium-phosphorus product is > 50 to 60 mg /dL . Serum calcium, phosphorus, and creatinine should be monitored closely. Oral phosphorus treatment is only indicated when there is concomitant hypophosphatemia (<2 mg/dL). 

Because phosphorus is excreted renally, hyperphosphatemia is common in ARF. Like potassium, large amounts of phosphorus are released into the circulation secondary to tissue breakdown during ARF. Control of hyperphosphatemia is important because as the calcium-phosphorus product (serum calcium in milligrams per deciliter multiplied by serum phosphorus in milligrams per deciliter) exceeds 55, the risk of developing metastatic calcification increases (see Chap. 44). Conversely, with initiation of dialysis, particularly CRRT, patients must be monitored for dialysis-induced hypophosphatemia. 

Osteoporosis and osteitis fibrosa cystica Metastatic calcifications vi. Neurologic changes Secondary hyperparathyroidism a. Etiology... 

Although all cases of renal insufficiency may lead to moderate hyperplasia of the parathyroid associated with mild signs of demineralization of the skeleton, only in those cases in which slow and progressive destruction of the renal parenchyma occurs does renal osteitis fibrosa cystica generalisata (a disease resembling von Recklinghausen s disease) develop. In these advanced cases, metastatic calcification in soft tissue may also be found. Renal biopsy may prove useful in the differential diagnosis of primary and secondary hyperparathyroidism. 

---