Calcium, absorption reabsorption renal

Vitamin D hormone is derived from vitamin D (cholecalciferol). Vitamin D can also be produced in the body it is formed in the skin from dehydrocholesterol during irradiation with UV light. When there is lack of solar radiation, dietary intake becomes essential, cod liver oil being a rich source. Metaboli-cally active vitamin D hormone results from two successive hydroxylations in the liver at position 25 ( calcifediol) and in the kidney at position 1 ( calci-triol = vit. D hormone). 1-Hydroxylation depends on the level of calcium homeostasis and is stimulated by parathormone and a fall in plasma levels of Ca or phosphate. Vit D hormone promotes enteral absorption and renal reabsorption of Ca and phosphate. As a result of the increased Ca + and phosphate concentration in blood, there is an increased tendency for these ions to be deposited in bone in the form of hydroxyapatite crystals. In vit D deficiency, bone mineralization is inadequate (rickets, osteomalacia). Therapeutic Liillmann, Color Atlas of Pharmacology... 

Cholecalciferol Regulate gene transcription via the vitamin D receptor Stimulate intestinal calcium absorption, bone resorption, renal calcium and phosphate reabsorption decrease parathyroid hormone (PTH) promote innate immunity inhibit adaptive immunity Osteoporosis, osteomalacia, renal failure, malabsorption Hypercalcemia, hypercalciuria the vitamin D preparations have much longer half-life than the metabolites and analogs... 

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

Q7 Calcium is present in both intracellular fluid (ICF) and ECF, but the concentration in the ECF is twice as high as that in the ICF. Calcium is found in both ionized and bound forms, and Ca2+ homeostasis is mainly controlled by parathyroid hormone, which increases absorption of calcium in the intestine and reabsorption in the nephron. Calcitonin also affects ECF calcium concentration by promoting renal excretion when there is an excess of calcium in the body. The normal kidney filters and reabsorbs most of the filtered calcium however, in renal disease this is reduced and blood calcium decreases. Calcium and phosphate imbalance can occur in patients with renal failure, leading to osteomalacia (defective mineralization of bone). Osteomalacia is mainly due to reduced production of 1,25-dihydroxycholecalciferol, an active form of vitamin D metabolized in the kidney. Deficiency of 1,25-dihydroxycholecalciferol reduces the absorption of calcium salts by the intestine. 

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." ... 

Calcium homeostasis is modulated by hormones (Fig. 2). Parathyroid hormone (PTH) is the most important calcium regulator. It is a hormone of 84 amino acids, and is secreted from the parathyroid glands in response to a low unbound plasma calcium. PTH causes bone resorption and promotes calcium reabsorption in the renal tubules, preventing loss in the urine. 1,25-dihydroxycholecalciferol (1.23 DHCC) maintains intestinal calcium absorption. This sterol hormone is formed from vitamin D (cholecalciferol). following hydroxylation in the liver (at carbon-25) and kidney (at carbon-1). However.hydroxylation in the kidney is PTH dependent.andsoeven (he absorption of calcium from the gut relies (albeit indirectly) on PTH. 

PTH is a polypeptide hormone that regulates plasma Ca +by affecting bone formation/resorption, renal Ca excretion/reabsorption, and calcitriol synthesis (thereby indirectly regulating G1 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. 

H5 ocalcemia is treated with PTH replacement that corrects the calcium deficit by promoting calcium absorption from the GI tract, promotes calcium reabsorption from the renal tubules, and activates Vitamin D. Calcitriol is a vitamin D analogue that promotes calcium absorption from the GI tract and secretion of calcium of bone to the bloodstream. 

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). 

Calcium homeostasis is maintained by hormonal regulation of the intestina absorption and renal reabsorption. During growth and lactation, body calcium requirements increase and the efficiency of calcium absorption can increase more than 60% compared with the adult steady-state conditions. With age and loss of estrogen stimulation this adaptive ability is blunted. 

Calcium (Ca ) Parathyroid hormone Calcitonin Magnesium (helps in calcium metabolism and intestinal absorption) Intestinal absorption Renal reabsorption Renal excretion... 

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. 

When calcium absorption is chronically low, because of low intakes, poor bioavailability, or conditions that impair intestinal absorption, there is a decrease in the serum ionized calcium concentration. This in turn stimulates the release of PTH, which returns serum calcium to normal by increasing renal calcium reabsorption, stimulating the renal production of 1,25(0H)2D3, and inducing bone reabsorption. The result of long-term calcium deficiency is accelerated bone loss in older individuals or the inability to fully achieve peak bone mass in younger individuals. 

A major regulator of Pi is PTH, whose role has been fairly well uncovered. PTH increases bone resorption of Pi (and calcium ions), it blocks renal tubular Pi reabsorption following glomerular filtration (whereas PTH favors calcium reabsorption), and it enhances intestinal Pi absorption (and calcium absorption) via the vitamin D hormone, l,25(OH)2 vitamin D. Other hormones have more modest effects on serum Pi concentration. 

The kidney is also sensitive to lead exposure, with kidney failure resulting from long-term exposure to toxic levels of lead. Furthermore, toxic levels of lead inhibit other functions of the kidney aside from the primary function of urine production. The nephron of a kidney, which is that portion where blood filtering and urine production takes place, is sensitive to lead. It is well known that the active form of vitamin is produced in the proximal tubules of the nephron. Decreased levels of vitamin D3 in the body results in decreased calcium absorption by the gut, and ultimately affect the strength of bones in a lead-exposed body. Increased levels of lead in blood can lead to protein-lead complexes in the nephron tubules. Gout may be a symptom of such toxicity due to increased reabsorption of uric acid into the bloodstream. Typical measures of renal failure (e.g., blood urea nitrogen, creatine) are elevated as a consequence of lead-induced renal failure. 

Parathyroid hormone, a polypeptide of 83 amino acid residues, mol wt 9500, is produced by the parathyroid glands. Release of PTH is activated by a decrease of blood Ca " to below normal levels. PTH increases blood Ca " concentration by increasing resorption of bone, renal reabsorption of calcium, and absorption of calcium from the intestine. A cAMP mechanism is also involved in the action of PTH. Parathyroid hormone induces formation of 1-hydroxylase in the kidney, requited in formation of the active metabolite of vitamin D (see Vitamins, vitamin d). 

Hydroxy vitamin D pools ia the blood and is transported on DBF to the kidney, where further hydroxylation takes place at C-1 or C-24 ia response to calcium levels. l-Hydroxylation occurs primarily ia the kidney mitochondria and is cataly2ed by a mixed-function monooxygenase with a specific cytochrome P-450 (52,179,180). 1 a- and 24-Hydroxylation of 25-hydroxycholecalciferol has also been shown to take place ia the placenta of pregnant mammals and ia bone cells, as well as ia the epidermis. Low phosphate levels also stimulate 1,25-dihydtoxycholecalciferol production, which ia turn stimulates intestinal calcium as well as phosphoms absorption. It also mobilizes these minerals from bone and decreases their kidney excretion. Together with PTH, calcitriol also stimulates renal reabsorption of the calcium and phosphoms by the proximal tubules (51,141,181—183). 

Two renal responses are unique to the thiazide and thiazidehke diuretics. With these compounds, Na+ excretion is increased, while Ca++ excretion is decreased, primarily and directly because of increased distal Ca++ reabsorption, secondarily and indirectly because of a compensatory elevation of proximal solute absorption, making this class of diuretics useful in treating hypercal-ciuria. This effect, which may not be evident upon initial administration of the drug, is particularly benehcial in individuals who are prone to calcium stone formation. 

Approximately two thirds of all renal stones contain calcium phosphate or calcium oxalate. Many patients with such stones exhibit a renal defect in calcium reabsorption that causes hypercalciuria. This can be treated with thiazide diuretics, which enhance calcium reabsorption in the distal convoluted tubule and thus reduce the urinary calcium concentration. Salt intake must be reduced in this setting, as excess dietary NaCl will overwhelm the hypocalciuric effect of thiazides. Calcium stones may also be caused by increased intestinal absorption of calcium, or they may be idiopathic. In these situations, thiazides are also effective, but should be used as adjunctive therapy with decreased calcium intake and other measures. 

It is now well established that l,25-(OH)2D3 is the active hormonal form of vitamin D3 [32], The production of l,25-(OH)2D3 in the kidney is regulated by dietary calcium and phosphate and also by changes in serum calcium and parathyroid hormone, which clearly highlight the hormonal nature of this compound. Functionally, the three classical actions of l,25-(OH)2D3 are to stimulate intestinal calcium and independently phosphate absorption, the mobilization of calcium from bone, and increase renal reabsorption of calcium. The focus of this review will be to explore the most recent concepts of vitamin D in regard to its metabolism and physiology, and with respect to the medicinal applications of vitamin D3 metabolites and analogues. 

The principal physiological role of vitamin D is in the maintenance of the plasma concentration of calcium. Calcitriol acts to increase intestinal absorption of calcium, to reduce its excretion by increasing reabsorption in the distal renal tubule, and to mobilize the mineral from bone - of the 25 mol of calcium in the adult body, 99% is in bone. The daily intake of calcium is around 25 mmol, and intestinal secretions add an additional 7 mmol to the intestinal contents 10 to 14 mmol of this is normally absorbed, with 18 to 22 mmol excreted in feces. Bone turnover accounts for exchange of 10 mmol of calcium between bone and plasma daily. The kidneys filter some 240 mmol of calcium daily, almost all of which is reabsorbed urinary excretion of calcium is about 3 to 7 mmol per day. 

As a consequence of the blockade of the Na, K, 2Cr-cotransporter, the diuresis produced by furosemide (frusemide) results in increased urinary excretion of sodium, potassium, chloride, calcium and magnesium ions. The losses of sodium, potassium and chloride are approximately 1750, 600 and 2150 mmol, respectively, after i.m. administration of furosemide (frusemide) at 1 mg/kg. Although these electrolyte losses are substantial, they are largely replaced (within the 24 h period following furosemide (frusemide) administration) by enhanced renal reabsorption as well increased ion absorption from the intestinal tract. In addition to this primary action, furosemide (frusemide) may have a lesser inhibitory effect on other chloride ion transporters and the drug can also inhibit carbonic anhydrase activity (Martinez-Maldonado Cordova 1990, Rose 1989,1991, Wilcox 1991). Finally, some of the renal and extrarenal effects of furosemide (frusemide) appear to be mediated through increased prostaglandin production. 

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