Hypocalcemia calcium absorption

Hypomagnesemia, often associated with hypocalcemia, is frequently encountered in heavy users of alcohol. Alcoholism sometimes is ascribed lo impaired inleslinal calcium absorption... 

Vitamin D-binding protein and its associated vitamin are lost in nephrotic urine. Biochemical abnormalities in nephrotic patients (children and adults) include hypocalcemia, both total (protein-bound) and ionized hypocalciuria, reduced intestinal calcium absorption and negative calcium balance reduced plasma 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol and, surprisingly, also 1,25-dihydroxycholecalciferol and blunted response to parathormon (PTH) administration and increased PTH levels. Clinically, both osteomalacia and hyperparathyroidism have been described in nephrotic patients, more commonly in children than in adults, but bone biopsies are commonly normal, and clinically significant bone disease is very rare in nephrotic subjects. There is, however, evidence that patients with renal failure accompanied by nephrotic range proteinuria may be particularly prone to develop renal osteodystrophy. 

Thus, a complex relationship exists among serum Ca + and phosphate, PTH, and vitamin D and its metabolites. Release of PTH in response to low serum Ca + directly mobilizes calcium from bone and increases synthesis of 1, 25-(0H)2D, which in turn mobilizes skeletal Ca + and causes increased intestinal calcium absorption. These effects raise the serum Ca level sufficiently to reduce PTH secretion. The effect of PTH on the kidneys occurs within minutes, whereas the effects of PTH on bone and (indirectly) on intestine take hours and days, respectively. An increase in serum phosphate acts in a way qualitatively similar to that of hypocalcemia to release PTH, increase excretion of phosphate in the proximal tubules, and decrease intestinal phosphate absorption. These events are mediated predominantly by the decrease in serum calcium that accompanies a rise in phosphate concentration. In addition, phosphate may inhibit 25-(OH)D-la-hydroxylase. 

The actions of thyrocalcitonin on the alimentary tract do not appear to be of major significance. Aliapoulios and Munson (Al) found that administration of the hormone to rats produced the expected hypocalcemia, even when the entire gastrointestinal tract had been removed. Clearly, changes in calcium absorption or fecal loss cannot be relevant to the immediate drop in plasma calcium level. However, previous fasting, or the administration of a low-calcium diet for some days, appears to sensitize the rat to the effects of thyrocalcitonin (H4, Kl). 

Hypocalcemia can result from inadequate dietary intake, decreased fractional calcium absorption (as seen with increasing age), or enhanced calcium excretion. To restore calcium homeostasis after hypocalcemia, PTH concentrations rise, and vitamin D metabolism increases to enhance intestinal calcium absorption (see Fig. 88-3), renal calcium reabsorption, and bone resorption. Fracture risk is greatest with low calcium intake and low fractional calcium absorption." ... 

BY PTH Even modest reductions of serum Ca stimulate PTH secretion. Acutely, the regulation of tubular Ca reabsorption by PTH suffices to maintain plasma Ca homeostasis. With more prolonged hypocalcemia, renal la-hydroxylase is stimulated this enhances the synthesis and release of calcitriol, which directly stimulates intestinal calcium absorption (Figure 61-3). Finally, PTH and the resulting increase in calcitriol also stimulate Ca release from bone. 

Mineral balance Hypocalcemia, hypomagnesemia, and a moderate reduction in 25-hydroxycholecalciferol have been attributed to omeprazole in a 67-year-old man, confirmed by rechallenge [62" ], and hypocalcemia in a 50-year-old woman [63" ]. Despite these and other case reports, suggesting interference by proton pump inhibitors with calcium absorption, two randomized, controlled, crossover trials in healthy volunteers and postmenopausal women showed no effect of esomeprazole or omeprazole on calcium absorption [64 , 65 ]. Other mechanisms (for example, increased excretion) should therefore be sought for hypocalcemia and an increased risk of osteoporotic fractures. 

Zaya NE, Woodson G. Proton pump inhibitor suppression of calcium absorption presenting as respiratory distress in a patient with bilateral laryngeal paralysis and hypocalcemia. Ear Nose Throat J 2010 89 78-80. 

If vitamin D has no effect on calcium absorption, it does affect calcium mobilization and thereby restores plasma concentrations of calcium. This finding explains why vitamin D deficiency was associated with hypocalcemia. The effect on the bone seems to require a synergetic action of vitamin D and parathormone. The 1,25-hydroxylated derivative seems to be the major active compound causing calcium release from the bone. The 25-hydroxyl derivative has, however, been shown to be active as well. Finally, vitamin D increases renal proximal tubular reabsorption of phosphate in normal and vitamin D deficient animals. Consequently phosphate excretion is decreased. Inasmuch as this effect occurs in parathyroidectomized animals, the effect of vitamin D or its metabolites must be direct. Again, the active metabolites are the 25 and 1,25-hydroxy derivatives. A calcium binding protein has been isolated from the kidney cortex, but its role in renal reabsorption is not known. 

Vitamin D deficiency in young children causes rickets. As a child becomes vitamin D deficient, this results in a decrease in the efficiency of intestinal calcium absorption. There is a decline in blood-ionized calcium, which causes the parathyroid glands to produce and secrete more parathyroid hormone (PTH). PTH tries to conserve calcium by enhancing tubular reabsorption of calcium in the kidney. However, in the face of developing hypocalcemia, which could disturb neuromuscular function and a wide variety of metabolic and cellular processes, the body calls upon l,25(OH)2D and PTH to mobilize stem cells to become functional osteoclasts, which, in turn, mobilize calcium from the skeleton. In addition, PTH causes a loss of phosphorus into the urine causing hypophosphatemia. Thus, in early vitamin D deficiency the serum calcium is normal it is the low serum phosphorus that causes the extracellular CaXP04 to be too low for normal mineralization of... 

Magnesium ion is essential for normal Ca " and K" metaboHsm. In acute experimental magnesium deficiency in humans, hypocalcemia occurs despite adequate calcium intake and absorption and despite normal renal and parathyroid functions. Negative K" balance is also observed. AH biochemical and clinical abnormaHties disappear upon restoration of adequate amounts of magnesium to the diet (64). 

Hypocalcemia directly increases PTH synthesis and release and inhibits calcitonin release. PTH in turn restores plasma calcium by initially stimulating transport of free or labile calcium from bone into the blood. PTH also increases renal 1,25-dihydroxycholecalciferol (1,25-(0H)2D3) production, which is the most active form of D3. 1,25-(0H)2D3 induces enterocyte differentiation in the intestine, which in turn results in increased absorption of calcium. Finally, during long periods of hypocalcemia, PTH can mobilize more stable calcium deep in the hydroxyapatite of bone by activating deep osteoclasts. 

Vitamin D analogs Calcifediol (Calderol) Calcitriol (Rocaltrol) Dihydrotachysterol (DHT, Hytakerol) Ergocalciferol (Calciferol, Drisdol) Generally enhance bone formation by increasing the absorption and retention of calcium and phosphate in the body useful in treating disorders caused by vitamin D deficiency, including hypocalcemia, hypophosphatemia, rickets, and osteomalacia... 

The metabolism of phosphorus (P) is largely related to that of calcium (Ca). The Ca P ratio in the diet affects the absorption and excretion of these elements (Harper 1969). Any increase in serum phosphorus results in a decrease of serum calcium by mechanisms which are still unknown. For example, increased serum phosphorus levels and decreased serum calcium levels are seen in uremia (renal retention of phosphorus), hypoparathyroidism, hypocalcemia (decreased serum calcium levels), and hyperphosphatemia (increased serum phosphorus levels), and the reverse is seen in hypercalcemia (increased serum calcium levels) and hyperparathyroidism. Hypophosphatemia (low serum phosphorus levels) is seen in ricketts (vitamin D deficiency) (Harper 1969 Tietz 1970). 

In patients with renal failure, the occurrence of conditioned zinc deficiency may be the result of a mixture of factors, which at present are ill defined. If 1,25-dihydroxycholecalciferol plays a role in the intestinal absorption of zinc, an impairment in its formation by the diseased kidney would be expected to result in malabsorption of zinc. It seems likely that plasma and soft tissue concentrations of zinc may be "protected in some individuals with renal failure by the dissolution of bone which occurs as a result of increased parathyroid activity in response to low serum calcium. In experimental animals, calcium deficiency has been shown to cause release of zinc from bone. In some patients who are successfully treated for hyperphosphatemia and hypocalcemia, the plama zinc concentration may be expected to decline because of the deposition of zinc along with calcium in bone. Thus, in the latter group in particular, a diet low in protein and high in refined cereal products and fat would be expected to contribute to a conditioned deficiency of zinc. Such a diet would be low in zinc. The patients reported by Mansouri et al. (37), who were treated with a diet containing 20-30 g of protein daily and who had low plasma concentrations of zinc, appear to represent such a clinical instance. Presumably the patients of Halsted and Smith (38) were similarly restricted in dietary protein. In other patients with renal failure whose dietary protein was not restricted, plasma zinc concentration were not decreased. Patients on dialysis had even higher levels, particularly... 

Acute symptomatic hypocalcemia may be seen in hospitalized patients for various reasons. Rapid remineralization of bone after surgery for primary hyperparathyroidism (hungry bone syndrome), treatment for hyperthyroidism, or treatment for hematological malignancy may result in hypocalcemia. Acute hemorrhagic or edematous pancreatitis is frequently complicated by hypocalcemia. Vitamin D deficiency may also be associated with hypocalcemia because of impaired intestinal absorption of calcium and skeletal resistance to PTH. Osteomalacia and rickets are discussed in a later section of this chapter. 

Osteitis fibrosa (hyperparathyroid bone disease) is the most common high-turnover bone disease. This disorder is caused by the high concentrations of serum PTH in secondary hyperparathyroidism. Secondary hyperparathyroidism is a consequence of the hypocalcemia associated with hyperphosphatemia and l,25(OH)2D deficiency. Hyperphosphatemia is a result of the kidneys inability to excrete phosphate. l,25(OH)2D deficiency results from the inability of the kidneys to synthesize l,25(OH)2 because of decreased renal mass and suppression of 25(OH)D-la-hydroxylase activity by high concentrations of phosphate. Deficiency of l,25(OH)2D leads to reduced intestinal absorption of calcium and reduced inhibition of PTH secretion by l,25(OH)2D. Skeletal resistance to PTH also contributes to the hypocalcemia and secondary hyperparathyroidism. 

Milhaud et al. (Mil), using intact rats, found that the prolonged hypocalcemia induced by repeated injections of thyrocalcitonin resulted in significantly increased absorption and retention of dietary calcium they also noted a reduction in the endogenous and total fecal calcium. These findings have largely been confirmed by Wase et al. (W2), who... 

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