Absorption of Calcium and Phosphate

The enteral absorption of calcium and phosphate after birth depends on a number of factors, including the amounts ingested, the types of foods eaten and the level of vitamin D. Under optimal circumstances, the amounts of calcium and phosphate incorporated into the body per kilogram per day following birth are only about one-third of those accumulated in utero. Since the growth of the baby s body mass is faster than the absorption of calcium and phosphate, the infant must normally borrow from and redistribute his existing bone... 

Three hormones serve as the principal regulators of calcium and phosphate homeostasis parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and the steroid vitamin D (Figure 42-2). Vitamin D is a prohormone rather than a true hormone, because it must be further metabolized to gain biologic activity. PTH stimulates the production of the active metabolite of vitamin D, l,25(OH)2D. l,25(OH)2D, on the other hand, suppresses the production of PTH. l,25(OH)2D stimulates the intestinal absorption of calcium and phosphate. l,25(OH)2D and PTH promote both bone formation and resorption in part by stimulating the proliferation and differentiation of osteoblasts and osteoclasts. Both... 

Effect of vitamin D on the intestine 1,25-diOH D3 stimulates intestinal absorption of calcium and phosphate. 1,25-diOH D3 enters the intestinal cell and binds to a cytosolic receptor. The 1,25-diOH D3-receptor complex then moves to the nucleus where it selectively interacts with the cellular DNA. As a result, calcium uptake is enhanced by an increased synthesis of a specific calcium-binding protein. Thus, the mechanism of action of 1,25-diOH D3 is typical of steroid hormones (see p. 238). 

The physiological role of vitamin D is to maintain calcium homeostasis. Phosphate metabolism is also affected. Vitamin D accomplishes its role by enhancing the absorption of calcium and phosphate from tte small intestines, promoting their mobilization from bone, and decreasing their excretion by the kidney. Also involved are parathyroid hormone and edeitonin. 

This active vitamin D metabolite (1,25 dihydroxycholecalciferol) is an important cofactor for intestinal calcium absorption, which involves calbindins (calcium binding proteins) in the intestine and kidney. Calcitriol is produced in the kidneys by the conversion of 25-hydroxycholecalciferol (calcidiol) and its formation is stimulated by a reduction of plasma calcium and/or phosphate and increased production of parathyroid hormone and prolactin (Figure 6.3). Calcitriol also inhibits the release of calcitonin and, together with PTH, increases the absorption of calcium and phosphate from the gastrointestinal tract and the kidneys. Growth hormone, glucocorticoids, estrogens, testosterone, and the thyroid hormones also influence calcium metabolism. 

VITAMIN D DEFICIENCY Vitamin D deficiency is associated with inadequate absorption of calcium and phosphate. The resulting decrease in Ca stimulates PTH secretion, which acts to restore plasma Ca + at the expense of bone. Plasma phosphate concentration will remain low due to the phosphaturic effect of PTH. In children, the failure to mineralize newly formed bone results in rickets, a growth disorder in which the long bones may be bowed due to inadequate calcification. 

V. The Absorption of Calcium and Phosphate 1. Studies in Intact Animals and in Man... 

It is no surprise that the interpretation of some of the early studies, e.g., that by Orr et al. (1923), was that vitamin D increases the absorption of calcium and phosphate. 

Wolhach and Bessey explain rickets as due to deficient absorption of calcium and phosphate and conclude that there is no reason to believe that the cells and matrices concerned in hone growth and maintenance are defective in rickets or are directly acted upon by the vitamin D. ... 

General metabolic significance. Vitamin D stimulates intestinal absorption of calcium and phosphate, renal reabsorption of these ions, deposition and mobilization of minerals in the hard tissue, controlling normal calcium and phosphate blood level by means of these processes. Molecular mechanism of the vitamin D effects most frequently conform to the effect of steroid hormones (induction of protein biosynthesis). 

Vitamin D consists of a group of similar steroid substances, all being metabolized to the active form of vitamin D, calcitriol or l,25(OH)2D3. Vitamin D is necessary for normal absorption of calcium and phosphate from both the intestine and the skeleton. Vitamin D deficiency results in low concentrations of these ions in the extracellular fluid and decreased mineralization of the osteoid in the skeleton. Therefore vitamin D deficiency causes development of rachitis in children and osteomalacia in adults. The circulating levels of calcitriol is influenced by hormonal control. Furthermore, a hormonal control is suggested to work by direct action on the enterocytes. 

Calcitriol increases the intestinal absorption of calcium and phosphate by stimulating the active system for transport of calcium. It also stimulates the synthesis of the calcium-binding protein in the mucosa cells. Calcitriol is more than five times as active as 25(OH)D3 with respect to its effect on the intestinal calcium absorption and more than 100 times as effective as an absorber of Ca ftom the skeleton. The concentration of calcitriol in plasma is about 70 pmol/liter, which is about 1000 times lower than the concentration of 25(OH)D3. 

Both are equally effective In man, and the latter Is often placed In the class of hormones since calciferol Is formed by the action of sunlight on 7-dehydrocholesterol In the skin (Frleden and Llpner, 1971) Vitamin D Increases bone sensitivity to parathyroid hormones and promotes Intestinal absorption of calcium and phosphate ... 

It is generally accepted that a normal secretion of hydrochloric acid by the stomach is necessary for optimal absorption of calcium and phosphate, better absorption being due to a lowering of the pH of the gastrointestinal tract. The presence of hypochlorhydria or achlorhydria therefore exerts an adverse influence upon calcium and phosphate absorption. 

Effects of Vitamin D Deficiency.—The vitamin regulates the absolute and relative absorption of calcium and phosphate solutes from the intestinal tract, and may be regarded as a calcio-kinetic, or calcium-distributing, vitamin. Avitaminosis D is characterised by —... 

Vitamin D is a family of closely related molecules that prevent rickets, a childhood disease characterized by inadequate intestinal absorption and kidney reabsorption of calcium and phosphate. These inadequacies eventually lead to the demineralization of bones. The symptoms of rickets include bowlegs,... 

Human parathyroid hormone (hPTH) is an 84 amino acid polypeptide that functions as a primary regulator of calcium and phosphate metabolism in bones. It stimulates bone formation by osteoblasts, which display high-affinity cell surface receptors for the hormone. PTH also increases intestinal absorption of calcium. 

Monsen, E. R., and Cook, J. D. (1976). Food iron absorption in human subjects. IV. The effects of calcium and phosphate salts on the absorption of nonheme iron. Am.. Clin. Nutr. 29, 1142-1148. 

Calcium and phosphate enter the body from the intestine. The average American diet provides 600-1000 mg of calcium per day, of which approximately 100-250 mg is absorbed. This figure represents net absorption, because both absorption (principally in the duodenum and upper jejunum) and secretion (principally in the ileum) occur. The amount of phosphorus in the American diet is about the same as that of calcium. However, the efficiency of absorption (principally in the jejunum) is greater, ranging from 70% to 90%, depending on intake. In the steady state, renal excretion of calcium and phosphate balances intestinal absorption. In general, over 98% of filtered calcium and 85% of filtered phosphate is reabsorbed by the kidney. The movement of calcium and phosphate across the intestinal and renal epithelia is closely regulated. Intrinsic disease of the intestine (eg, nontropical sprue) or kidney (eg, chronic renal failure) disrupts bone mineral homeostasis. 

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... 

Vitamin D is a precursor for a number of compounds that increase intestinal absorption and decrease renal excretion of calcium and phosphate. Metabolites of vitamin D and their pharmacologic analogs are typically used to increase blood calcium and phosphate levels and to enhance bone mineralization in conditions such as osteodystrophy, rickets, or other situations where people lack adequate amounts of vitamin D. Vitamin D analogs such as calcitriol have also been combined with calcium supplements to help treat postmenopausal osteoporosis,4,9 and to treat bone loss caused by antiinflammatory steroids (glucocorticoids see Chapter 29 28.76 Specific vitamin D-related compounds and their clinical applications are listed in Table 31-5. 

Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption... 

Phosphates are important because they affect the absorption of calcium and other elements. The absorption of inorganic phosphorus depends on the amount of calcium, iron, strontium, and aluminum present in the diet. Chapman and Pugsley (1971) have suggested that a diet containing more phosphorus than calcium is as detrimental as a simple calcium deficiency. The ratio of calcium to phosphorus in bone is 2 to 1. It has been recommended that in early infancy, the ratio should be 1.5 to 1 in older infants, 1.2 to 1 and for adults, 1 to 1. The estimated annual per capita intake in the United States is 1 g Ca and 2.9 g P, thus giving a ratio of 0.35. The danger in raising phosphorus levels is that calcium may become unavailable. 

Q4 The parathyroids produce a peptide hormone, PTH, which controls the level of calcium in the body. A sensor on the surface of the parathyroid cells monitors blood calcium concentration and PTH is secreted in response to a fall in plasma calcium ion concentration. An increase in the level of PTH leads to hypercalcaemia (raised blood calcium) conversely, a reduction in the level of PTH leads to hypocalcaemia. PTH acts on the kidney to reduce reabsorption of phosphate and at the same time to increase reabsorption of calcium. In addition, it promotes the release of calcium and phosphate into the blood by activating osteoclasts, which break down the inorganic matrix of bone. PTH also increases the absorption of calcium by the mucosal cells of the intestine. The latter is a rather slow, indirect action mediated by PTH stimulation of calcitriol secretion by the kidney. 

Actions are complex. Vitamin D promotes the active transport (absorption) of calcium and therefore of phosphate from the gut, to control, with parathormone, the mineralisation of bone and to... 

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. 

SEDA-22, 172) (1,2). However, hypercalcemia has also been reported in a few patients using no more than the recommended doses (3,4). Calcipotriol exerts its effects on systemic calcium homeostasis by increasing intestinal absorption of calcium and probably phosphate. This results in suppression of parathyroid hormone and 1,25-dihydroxycolecalciferol (5). 

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. 

PTH stimulates demineralization of bone and release of calcium and phosphate into the blood by stimulating osteoclast formation and activity, increases small bowel absorption of calcium ion, and acts directly on the kidney to suppress calcium ion excretion in the urine. 

Age is an important determinant of lead metabolism (US EPA 1986), there being a higher absorption from the gastrointestinal tract in infants than in adults. Simultaneous intake of lead, calcium and/or phosphate may reduce the gastrointestinal absorption of lead (Heard and Chamberlain 1984, James etal. 1985). Milk is a major source of both calcium and phosphorus, but it seems to contain several components that counteract the expected effects of calcium and phosphate, and this may lead to an increased (rather than decreased) lead uptake. It is not known which factor might be responsible for the increased lead uptake. 

Vitamin D increases serum calcium and phosphate, with calcitriol d.25rOH], vitamin D) being the major derivative responsible for promoting their intestinal absorption. Calciferol and calcitriol decrease renal excretion of calcium and phosphate. Parathyroid hormone, not vitamin D. acts via cAMP. The cause of Paget s disease is obscure. The answer is (C). 

Vitamin D is required for efficient absorption of calcium and phosphorus in the intestinal trad, and it is also necessary for calcium and phosphorus homeostasis within the body. Deficiency of vitamin D will, therefore, lead to calcium deficiency and will affect processes such as bone formation and egg-shell production. Bone mineralisation is dependent on the maintenance of Gi and phosphate levels. The effect of vitamin D on these processes is mediated by calbindin and is discussed in Section 10.6. Aluminium toxicity is, at least in part, accounted for by disturbance of calcium homeostasis. Aluminium compounds reduce vitamin D-dependent Gi absorption in chicks. They act by reducing the intestinal calbindin concentration (Dunn et al, 1993). 

Essentially alike in all species is the increased loss of calcium and phosphate in the feces as compared with proper controls. The nature of this loss will be discussed in the chapter on absorption. It is a fact that the ability to absorb calcium is of primary importance in the development of rickets in all species. There are, however, some variations from species to species, and these may be usefully mentioned here. 

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