Vitamin D (Calcitriol)
Bioactive vitamin D or calcitriol is a steroid hormone that has long been known for The major inducer of 1-alpha-hydroxylase is parathyroid hormone; it is also. de calcitriol podría disminuir la reserva intercambiable de calcio independiente de la The relationship between PTH and serum calcium is a sig- moidal curve. Objective. To review the inter-relationships between calcium, phosphorus, PTH and calcitriol are the main regulators of calcium homeostasis.
These interactions allow conservation of calcium in the extracellular fluid ECF volume by renal tubular reabsorption, increased intestinal transport of calcium from the diet, and internal redistribution of calcium from bone. The skeleton serves as a major supply of calcium and phosphorus when intestinal absorption and renal reabsorption are inadequate to maintain the normal serum calcium concentrations. Bone calcium mobilization is important in the acute regulation of blood calcium.
Calcium and phosphorus can be mobilized from readily available calcium phosphate in the bone ECF compartment, but these stores are rapidly depleted. The osteoblast is critical in limiting the distribution of calcium and phosphate between bone and ECF, as exchangeable bone water is separated from ECF water by the combined membranes of osteoblasts lining bone surfaces.
For greater or prolonged release of calcium from bone, osteoclastic bone resorption must be activated. Osteoclasts secrete acid and proteases that result in the dissolution of the mineralized matrix of bone and thus mobilize calcium and phosphorus.
The extracellular iCa concentration is the fraction of total calcium that is actively regulated. When blood calcium concentration falls, PTH secretion is stimulated. PTH exerts direct effects on bone and kidney and indirect effects on the intestine through calcitriol.
Calcitriol, in turn, increases calcium absorption from the intestine. Calcitriol participates with PTH to stimulate osteoclastic bone resorption. Calcitriol is necessary for differentiation of osteoclasts from precursor mononuclear cells. At high pharmacologic doses, calcitriol can stimulate bone without PTH following actions on osteoblasts that subsequently liberate one or more factors that activate osteoclastic bone resorption.
PTH increases osteoclast number and stimulates osteoclast function to increase bone resorption and the release of calcium from bone to blood.
Calcitriol also induces renal transport mechanisms activated by PTH that increase tubular reabsorption of calcium from the glomerular filtrate, thus preventing calcium loss in urine. In addition, calcitriol exerts important inhibition of parathyroid gland PTG gene transcription for the synthesis of PTH. Vitamin D Compounds Vitamin D is a prohormone 5 that undergoes a two-step bioactivation to calcitriol as the most biologically active metabolite Figure 1.
PTH & Vit D Physiology - Basic Science - Orthobullets
It has been widely viewed that vitamin D2 and vitamin D3 are equipotent in people. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. The vitamin D receptor binds several forms of cholecalciferol. Its affinity for 1,dihydroxycholecalciferol is roughly times that for hydroxycholecalciferol, which explains their relative biological potencies.
Physiological Effects of Vitamin D Vitamin D is well known as a hormone involved in mineral metabolism and bone growth. Its most dramatic effect is to facilitate intestinal absorption of calcium, although it also stimulates absorption of phosphate and magnesium ions. In the absence of vitamin D, dietary calcium is not absorbed at all efficiently. Vitamin D stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood.
The best-studied of these calcium transporters is calbindin, an intracellular protein that ferries calcium across the intestinal epithelial cell. Numerous effects of vitamin D on bone have been demonstrated. As a transcriptional regulator of bone matrix proteins, it induces the expression of osteocalcin and suppresses synthesis of type I collagen.
In cell cultures, vitamin D stimulates differentiation of osteoclasts. However, studies of humans and animals with vitamin D deficiency or mutations in the vitamin D receptor suggest that these effects are perhaps not of major physiologic importance, and that the crutial effect of vitamin D on bone is to provide the proper balance of calcium and phosphorus to support mineralization. It turns out that vitamin D receptors are present in most if not all cells in the body.
Additionally, experiments using cultured cells have demonstrated that vitamin D has potent effects on the growth and differentiation of many types of cells.
These findings suggest that vitamin D has physiologic effects much broader that a role in mineral homeostasis and bone function. As one example, many immune cells not only express vitamin D receptors, but are capable of synthesizing active vitamin D, and deficiency in vitamin D has been associated with increased incidence of autoimmune disease and susceptibility to disease.
Calcitriol - Frequestly Ased Questions
Disease States Vitamin D deficiency: The classical manifestations of vitamin D deficiency is rickets, which is seen in children and results in bony deformaties including bowed long bones.
Deficiency in adults leads to the disease osteomalacia.
Both rickets and osteomalacia reflect impaired mineralization of newly synthesized bone matrix, and usually result from a combination of inadequate exposure to sunlight and decreased dietary intake of vitamin D. Vitamin D deficiency or insufficiency occurs in several other situations, which you might predict based on the synthetic pathway described above: Genetic defects in the vitamin D receptor: Severe liver or kidney disease: Insufficient exposure to sunlight: Elderly people that stay inside and have poor diets often have at least subclinical deficiency.
Ironically, it appears that hypovitaminosis D is very common in some of the most sunny countries in the world - the cause of this problem is the cultural dictate that women be heavily veiled when outside in public. Sunscreens, especially those with SPF ratings greater than 8, effectively block synthesis of vitamin D in the skin. However, people that use such sunscreens religiously live in industrial countries where many foods are supplemented with vitamin D, and vitamin D deficiency is thereby averted by dietary intake.
Excessive exposure to sunlight does not lead to overproduction of vitamin D. Vitamin D toxicity is inevitably the result of overdosing on vitamin D supplements.