The homeostatic regulation of Pi in blood is primarily controlled by PTH, but several other hormones also exert influences on it. The major sites of regulation are the kidneys and the gut. PTH acts on the renal tubules to inhibit Pi reabsorption, while at the same time enhancing Ca reabsorption. The response of the kidneys to the action of PTH is the primary route of loss of Pi from the body. A secondary route is the small intestine, through which intestinal secretions from glands within the serosa of the intestinal lining remove Pi from the bloodstream to the gut lumen. This route of loss of Pi ions is called endogenous fecal excretion, and the quantity of Pi lost by this route may be almost as great as renal losses over a 24-hour period.
Absorption of an excess of Pi tends to lower the blood Ca ion concentration, which then triggers the secretion of PTH from the parathyroid glands. The role of circulating Pi in the secretion of PTH has been investigated in animal models and in human subjects to establish the connection with high dietary phosphorus intake. As mentioned, the absorption of Pi ions is rapid following a meal, much more so than for calcium ions. When an excess of Pi ions exists in the blood, the Pi concentration increases; this change, in turn, drives down the Ca ion concentration through a mechanism involving ionic binding between the two ions.
The net reduction in the concentration of Ca ions then stimulates the secretion of PTH. In turn, PTH enables the transfer of residual circulating Ca and Pi ions into the bone fluid compartment and into other extravascular compartments of the body. (Some investigators suggest that calcitonin, another calcium-regulating hormone, is involved in the movement of these ions into bone and, hence, in the conservation of calcium after a meal.) The persistently elevated PTH, however, tends to undo calcium conservation in the skeleton because this hormone continuously stimulates the reverse transfer of Ca and Pi ions from bone to blood (Calvo et al. 1990). The net result is that the skeleton loses bone mineral when PTH is elevated, even within the normal range of blood concentration, over extended periods of time. (The actual site of loss of this Ca is the gut, which has a poorly regulated secretion of Ca ions through intestinal glands.) PTH also has other roles in the kidney that, in effect, contribute to Ca retention by the body and to the elimination of Pi via urinary excretion.
PTH is considered the major hormone regulating Pi homeostasis because of its powerful roles in enhancing renal and, possibly, intestinal Pi losses while, at the same time, conserving calcium ions. When PTH is elevated, renal Pi reabsorption is largely inhibited, and similarly, the secretion of Pi ions by intestinal mechanisms is enhanced (although an understanding of this route of Pi loss is less established). PTH also acts on bone tissue to increase the transfer of calcium ions from the bone fluid compartment (BFC) and from the resorption of mineralized bone tissue to the blood plasma to restore the calcium ion concentration. By these same actions of PTH, Pi ions are also indirectly transferred from the BFC and bone to the blood.
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