Calcium homeostasis hormonal regulation

A major regulator of bone metabolism and calcium homeostasis, parathyroid hormone (PTH) is stimulated through a decrease in plasma ionised calcium and increases plasma calcium by activating osteoclasts. PTH also increases renal tubular calcium re-absorption as well as intestinal calcium absorption. Synthetic PTH (1-34) has been successfully used for the treatment of osteoporosis, where it leads to substantial increases in bone density and a 60-70% reduction in vertebral fractures. 

In addition to these hormonal regulators, calcium and phosphate themselves, other ions such as sodium and fluoride, and a variety of drugs (bisphosphonates, plicamycin, and diuretics) also alter calcium and phosphate homeostasis. 

PTH works with two other primary hormones— calcitonin and vitamin D—in regulating calcium homeostasis. These three hormones, as well as several other endocrine factors, are all involved in controlling calcium levels for various physiologic needs. How these hormones interact in controlling normal bone formation and resorption is of particular interest to rehabilitation specialists. Regulation of bone mineral homeostasis and the principal hormones involved in this process are presented in the following section. 

Consequently, bone is a rather dynamic tissue that is constantly undergoing changes in mineral content and internal structure. The balance between bone resorption and formation is controlled by the complex interaction of local and systemic factors. In particular, several hormones regulate bone formation and help maintain adequate plasma calcium levels. The primary hormones involved in regulating bone mineral homeostasis are described below. 

The thyroid and parathyroid glands serve a number of vital endocrine functions. The thyroid gland synthesizes and secretes the thyroid hormones T3 and T4. These hormones are important regulators of cellular metabolism and metabolic rate. Thyroid hormones also interact with other hormones to facilitate normal growth and development. The parathyroid glands control calcium homeostasis through the release of PTH. This hormone is crucial... 

Parathyroid hormone (PTH) is an 84-amino acid polypeptide hormone that mediates bone remodeling and is an essential regulator of calcium homeostasis. Prolonged exposure to PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone... 

Figure 30-5. Regulation of calcium homeostasis by the combined action of 1,25-dihydroxy vi ta m in D and parathyroid hormone (PTH). ECF, extracellular fluid.

Under normal conditions each of the two million nephrons of the kidney work in an organized approach to filter, reabsorb, and excrete various solutes and water. The kidney is a primary regulator of sodium and water as well as acid-base homeostasis. The kidney also produces hormones necessary for red blood cell synthesis and calcium homeostasis. Impairment of normal kidney function is often referred to as renal insufficiency. Based on the time course of development, renal insufficiency has historically been divided into two broad categories. Acute renal failure (ARF) refers to the rapid loss of renal function over days to weeks. Chronic kidney disease (CKD)", also called chronic renal insufficiency (CRI) by some, is defined as a progressive loss of function occurring over several months to years, and is characterized by the gradual replacement of normal kidney architecture with interstitial fibrosis. Progressive kidney disease or nephropathy is... 

The vitamin D receptor (VDR/NR1I1) is a member of the superfamily of steroid hormone receptors. It regulates calcium homeostasis, cell proliferation, and differentiation, and exerts immunomodulatory and antimicrobial functions [119]. VDR binds to and mediates the calcemic effects of calcitriol (la,25-dihydroxy vitamin D3) after forming an heterodimer with RXR. la,25-dihydroxyvitamin D3 negatively regulates its own synthesis by repressing the 25-hydroxyvitamin D3 la-hydroxylase (CYP27B1) in a cell-type selective event that involves different combinations of multiple VDR response elements [120, 121]. 

The parathyroid hormone regulates ionic calcium homeostasis in extracellular fluids by a direct action on the skeleton. It also promotes the renal excretion of phosphorus and produces other physiological effects which are not obviously related to its calcemic action. 

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. 

The significance of the enzyme is due to the pleiotropic actions of the active form of vitamin D, la,25-dihydroxyvitamin Dj, which include regulation of calcium homeostasis, control of bone cell differentiation, and modification of immune responses. The la-hydroxylation reaction is rate limiting and hormonally controlled. The expression of the gene is usually tightly regulated (yide supra), but gene defects are... 

FIGURE 61-3 Calcium homeostasis and its regulation by parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D. 

Parathyroid hormone (PTH), vitamin D and calcitonin work in synchrony to regulate calcium homeostasis (not presented in tables). PTH is an 84 amino acid chain secreted by the parathyroid glands in response to low serum calcium. PTH induces bone resorption, which liberates calcium into the bloodstream. These actions are dependent on adequate serum concentrations of 1,25-dihydroxy cholecalciferol (a derivative of vitamin D). Bone resorption is counterregulated by calcitonin, which inhibits osteoclasts (the cells which degrade bone). 

Similarly, approximately 500 to 600 g of phosphate are present, 85% of which Is found in the bone. The normal plasma concentration of calcium Is approximately 4.5 to 5.7 mEq/L, 50% of which Is protein bound. The remainder of the calcium is either complexed to corresponding counterions (46%) or exists in its ionized form (4%). It Is only the ionized form of calcium that is tightly hormonally regulated (varies less than 5-10%) (1,2). Because serum calcium concentrations fluctuate, so do the plasma levels of the hormones associated with calcium homeostasis. Serum phosphorous levels vary with age, diet, and hormonal status. The most common... 

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. 

The concentration of ionized calcium in serum is closely regulated because it has profound effects on the function of nerves and muscles, blood clotting, and hormone secretion. The principal regulators of calcium homeostasis in humans and most terrestrial vertebrates are PTH and the active form of vitamin D, 1,25(0H)2 vitamin D3 (Figure 2). 

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