Vitamin calcium uptake

Calcium is the major mineral component of bone and normal repair and remodelling of bone is reliant on an adequate supply of this mineral. Calcium uptake in the gut, loss through the kidneys and turnover within the body are controlled by hormones, notably PTH and 1,25 dihydroxy cholecalciferol (1,25 DHCC or 1,25 dihydroxy vitamin D3 or calcitriol). Refer to Figure 8.12 for a summary of the involvement of PTH and vitamin D3 in controlling plasma calcium concentration. These two major hormones have complementary actions to raise plasma calcium concentration by promoting uptake in the gut, reabsorption in the nephron and bone resorption. Other hormones such as thyroxine, sex steroids and glucocorticoids (e.g. cortisol) influence the distribution of calcium. 

Vitamin D (calciferol) Produced in skin by action of ultraviolet Controls calcium uptake into the body and... 

Vitamin D3, also called cholecalciferol, is normally formed in the skin from 7-dehydrocholesterol in a photochemical reaction driven by the UV component of sunlight (Fig. 10-20). Vitamin D3 is not itself biologically active, but it is converted by enzymes in the liver and kidney to 1,25-dihydroxycholecalciferol, a hormone that regulates calcium uptake in the intestine and calcium levels in kidney and bone. Deficiency of vitamin D... 

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). 

Vitamin D Cholecalciferol Ergocalciferol 1,25-Dihydroxy- cholecalciferol Calcium uptake 1 i... 

Vitamin D (cholecalciferol ergocalciferol) has its active form as 1,25-dihydroxylchole-calciferol. It is responsible for calcium uptake, and a deficiency of the vitamin results in rickets (in children) and osteomalacia (in adults). The symptoms of both syndromes are soft, pliable bones. High levels of vitamin D are toxic. 

Vitamin D3 is a precursor of the hormone 1,25-dihy-droxyvitamin D3. Vitamin D3 is essential for normal calcium and phosphorus metabolism. It is formed from 7-dehydrocholesterol by ultraviolet photolysis in the skin. Insufficient exposure to sunlight and absence of vitamin D3 in the diet leads to rickets, a condition characterized by weak, malformed bones. Vitamin D3 is inactive, but it is converted into an active compound by two hydroxylation reactions that occur in different organs. The first hydroxylation occurs in the liver, which produces 25-hydroxyvita-min D3, abbreviated 25(OH)D3 the second hydroxylation occurs in the kidney and gives rise to the active product 1,25-dihydroxy vitamin D3 24,25 (OH)2D3 (fig. 24.13). The hydroxylation at position 1 that occurs in the kidney is stimulated by parathyroid hormone (PTH), which is secreted from the parathyroid gland in response to low circulating levels of calcium. In the presence of adequate calcium, 25(OH)D3 is converted into an inactive metabolite, 24,25 (OH)2D3. The active derivative of vitamin D3 is considered a hormone because it is transported from the kidneys to target cells, where it binds to nuclear receptors that are analogous to those of typical steroid hormones. l,25(OH)2D3 stimulates calcium transport by intestinal cells and increases calcium uptake by osteoblasts (precursors of bone cells). 

Although bone is not considered a major calcium sensing organ in humans, the cells of bone tissue control over 99% of the human body s calcium content. The principal calcium sensors that regulate bone calcium uptake and release are in the parathyroid glands. Bone function is also modified by vitamin D and by calcium transport in the kidney and intestine. These indirect mechanisms of controlling bone calcium metabolism are beyond the scope of our considerations here. In spite of processing... 

Q13 Osteomalacia and osteoporosis are complications of celiac disease. The mineral in bone is mainly calcium phosphate a supply of calcium is therefore needed for bone growth and replacement. Calcium is absorbed by active mechanisms in the duodenum and jejunum, facilitated by a metabolite of vitamin D. It is also passively absorbed in the ileum and specific calcium binding proteins are present in the intestinal epithelial cells. Loss of absorptive cells and calcium binding proteins markedly decreases calcium uptake and limits its availability for bone growth and repair. 

With the isolated perfused duodenum, there is a rapid increase in calcium transport in response to the addition of calcitriol to the perfusion medium. Isolated enterocytes and osteoblasts also show a rapid increase in calcium uptake in response to calcitriol. It is not associated with changes in mRNA or protein synthesis, but seems to be because of recruitment of membrane calcium transport proteins from intracellular vesicles to the cell surface. It is inhibited by the antimicrotubule compound colchicine. It can only be demonstrated in tissues from animals that are adequately supplied with vitamin D in vitamin D-deficient animals, the increase in intestinal calcium absorption occurs only more slowly, together with the induction of calbindin. 

Early studies showed that, after the administration of [ H]cholecalciferol or ergocalciferol to vitamin D-deficient animals, there is marked accumulation of [ H] calcitriol in the nuclei of intestinal mucosal cells. Physiological doses of vitamin D cause an increase in the intestinal absorption of calcium in deficient animals the response is faster after the administration of calcidiol and faster stUl after calcitriol. There are two separate responses of intestinal mucosal cells to calcitriol a rapid increase in calcium uptake that is due to recruitment of calcium transporters to the cell surface (Section 3.3.2) and a later response from the induction of a calcium binding protein, calbindin-D. 

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. 

When there is adequate sunlight, no dietary source of the vitamin is required. Indeed, an argument can be made that the calciferols are not normal components of the diet. In the United States, it is added to milk, other dairy products, and dairy substitutes. Fish is about the only natural food source. Cholecal-ciferol is produced in the body from endogenously synthesized 7-dehydrocholecalciferol (Fig. 8.10). Consistent with a hormone model, excess amounts of cholecalcdferol can result in excess calcium uptake from the intestinal tract, leading to calcification of soft tissues. 

PTH also acts to increase absorption of calcium ion by the small intestine. It does this indirectly by promoting the formation of active vitamin D in the kidney. PTH acts on the final, rate-limiting step in vitamin D synthesis, the formation of 1,25-dihydroxycholecalciferol in the kidney. If PTH is low, formation of the inactive derivative, 24,25-dihydroxycholecalciferol, is stimulated instead. Vitamin D acts on intracellular receptors in the small intestine to increase transcription of genes encoding calcium uptake systems, to up-regulate their expression. 

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. 

Some drugs, for example anticonvulsants phenytoin, phenobarbital and corticosteroids can lead to osteomalacia and rickets by depressing vitamin D dependent calcium uptake in the intestine. 

The several forms of vitamin D play a major role in the regulation of calcium and phosphorus metabolism. One of the most important of these compounds, vitamin D3 (cholecalciferol), is formed from cholesterol by the action of ultraviolet radiation from the Sun. Vitamin Dg is further processed in the body to form hydroxylated derivatives, which are the metabolically active form of this vitamin (Figure 8.30). The presence of vitamin Dg leads to increased synthesis of a Ga -binding protein, which increases the absorption of dietary calcium in the intestines. This process results in calcium uptake by the bones. 

Meador J (2006) Rationale and procedures for using the tissue-residue approach for toxicity assessment and determination of tissue, water, and sediment quality guidehnes for aquatic organisms. Human Ecol Risk Assess 12 1018-1073 Peakall DB (1969) Effect of DDT on calcium uptake and vitamin D metabohsm in birds. Nature 224 1219-1220... 

The K. is the site of synthesis of Erythropoietin (see) and Renin (see). Renin is synthesized in the juxtaglomerular cells it releases Angiotensin (see), which in turn stimulates the release of aldosterone by the adrenal cortex. 25-Hydroxycholecalciferol (produced in the liver from vitamin D3 or cholecalci-ferol) is converted by the kidney into 1,25-dihydroxy-cholecalciferol, which promotes calcium uptake by the intestine and calcium mobilization in bone. 

A number of factors have been suspected in calcium transport ionic exchange, a calcium sensitive ATPase, a calcium binding protein, vitamin D, parathormone, cortisone. Calcium uptake is depressed by sodium and enhanced if one-third of the sodium is replaced by mannitol. It appears that sodium is not required for calcium uptake or transepithelial transfer. The intestinal brush border contains a calcium-sensitive magnesium dependent ATPase. In contrast to the K, Na" ATPase, the enzyme is not inhibited by ouabain. Vitamin D induces its appearance. The exact role of the ATPase remains unresolved. 

The claimed health-promoting activities exerted by bifidobacteria are numerous, and include establishment of a healthy microbiota in preterm infants, cholesterol reduction, lactose intolerance, prevention of infectious diarrhea, prevention of cancer, protection against infectious diseases, modulation of mucosal barrier function, amino acid and vitamin production, inhibition of nitrate reduction, stimulation of calcium uptake by enterocytes, short-chain fatty acid production, stimulation of intestinal epithelia through induction of anti-inflammatory c5dokine interleukin (IL)-IO and junctional adhesion molecules. ... 

In all of these actions, the role of calcitriol seems to be the induction or maintenance of synthesis of calcium-binding proteins, and the effects are secondary to increased calcium uptake into the target cells. Several of these actions are also modulated by vitamin A as discussed in section 11.2.3.2, vitamin A (RXR) receptors form heterodimers with calcitriol receptors, so that both vitamins are required together for some actions. 

The amount of each element required in daily dietary intake varies with the individual bioavailabihty of the mineral nutrient. BioavailabiUty depends both on body need as deterrnined by absorption and excretion patterns of the element and by general solubiUty, and on the absence of substances that may cause formation of iasoluble products, eg, calcium phosphate, Ca2(P0 2- some cases, additional requirements exist either for transport of substances or for uptake or binding. For example, calcium-binding proteias are iavolved ia calcium transport an intrinsic factor is needed for vitamin cobalt,... 

Parathyroidectomy is a treatment of last resort for sHPT, but should be considered in patients with persistently elevated iPTH levels above 800 pg/mL (800 ng/L) that is refractory to medical therapy to lower serum calcium and/or phosphorus levels.39 A portion or all of the parathyroid tissue may be removed, and in some cases a portion of the parathyroid tissue may be transplanted into another site, usually the forearm. Bone turnover can be disrupted in patients undergoing parathyroidectomy whereby bone production outweighs bone resorption. The syndrome, known as hungry bone syndrome, is characterized by excessive uptake of calcium, phosphorus, and magnesium for bone production, leading to hypocalcemia, hypophosphatemia, and hypomagnesemia. Serum ionized calcium levels should be monitored frequently (every 4 to 6 hours for the first 48 to 72 hours) in patients receiving a parathyroidectomy. Calcium supplementation is usually necessary, administered IV initially, then orally (with vitamin D supplementation) once normal calcium levels are attained for several weeks to months after the procedure. 

There are four parathyroid glands, which are situated behind the thyroid. They produce parathyroid hormone (PTH), a peptide which interacts with vitamin D to control the level of calcium in the blood. PTH stimulates release of calcium from bone and increases the uptake of calcium by the kidney tubules from the glomerular hltrate. 

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