The principal organs of the body involved in the maintenance of calcium and phosphate homeostasis are the intestine, bone, and kidney. It is here that the four calcium-regulating hormones, PTH, CT, 1,25(OH)2D3, and FGF23 (a phosphate-regulating hormone) initiate an integrated set of biological responses that results in maintenance of calcium and phosphorus homeostasis. The steroid hormone 1α,25(OH)2D3 is the primary stimulator of the intestinal absorption of both Ca2+ and H2PO4−. The calcium uptake process is regulated according to the needs of the animal. Once the absorbed Ca2+ and H2PO4−/HPO42− from the intestine arrives in the plasma, a delicate hormonally mediated balancing of the concentrations of Ca2+ and H2PO4−/ HPO42− occurs in both the skeleton, between bone accretion and bone mobilization, and in the kidney tubules, between urinary excretion and urinary reabsorption. In the event that the dietary availability of Ca2+ and HPO4−/HPO42− is diminished, the balance is tipped in favor of increased bone mobilization to release small quantities of both Ca2+ and phosphate to meet the stringent requirement of maintaining a constant serum Ca2+ level. Thus, the serum Ca2+ concentration may become elevated by stimulation of intestinal Ca2+ absorption, bone Ca2+ mobilization, or stimulation of the tubular reabsorption of Ca2+ in the kidney.

Conversely, the serum Ca2+ can be lowered by increasing bone formation and inhibiting the renal tubular reabsorption of Ca2+. It is clear that, in the event that there is a dietary shortage of calcium and/or phosphate, the bone is the central organ in calcium and phosphate metabolism, acting as a replacement source to elevate serum calcium and/or phosphate concentrations.

The underlying foundation of the aqueous solubility product, Ksp, for [Ca2+] × [H2PO4−/HPO42−] strictly governs the permissible changes in blood [Ca2+] and blood [H2PO4−/HPO42−]. The value of the Ksp is ~1 × 10⁻⁷ M. Thus, if the Ksp is exceeded in vivo, then the precipitation of the excess calcium and phosphate will likely occur in the kidney and/or heart and arteries. This soft tissue calcification can damage normal tissue by large amorphous calcium deposits or by the formation of kidney stones. As a general rule, when the hormonal regulation of serum calcium is elevated, there is an associated fall in serum phosphate concentrations, or vice versa.

The US Institute of Medicine (2010) Recommended Dietary Allowance (RDA) average daily intakes for calcium vary from 700 mg/day for 1–3 years old to 1,200 mg/day for >70 years of age.

Figure 1 is a schematic diagram illustrating the 24-hr “metabolic balance” of calcium and phosphorus metabolism in a normal adult male. Calcium and phosphorus (as phosphate) are both absorbed into the body primarily in the duodenum and jejunum regions of the intestine. In addition to the ~900 mg/ day calcium ingested from the diet (for this example) ~600 mg is added to the intestinal contents by pancreatic and intestinal secretions. Of the ~1500 mg of total calcium present in the lumen of the intestine, ~850 mg is absorbed by the intestinal epithelial cells and trans ported to the blood compartment, leaving the remaining ~650 mg to be excreted in the feces.

Fig1. Schematic model of calcium and phosphorus metabolism in an adult man having a calcium intake of 900 mg/day and a phosphorus intake of 900 mg/day. All numerical values are milligrams per day. All entries relating to phosphate are calculated as phosphorus, and are enclosed in ovals. Entries related to calcium are enclosed in rectangles.

After the newly absorbed Ca2+ has entered the extracellular pool, it is in constant exchange with the Ca2+ already present in the extracellular and intracellular fluid compartments of the body and in certain compartments of the bone and the kidney’s glomerular filtrate. The entire extracellular pool of 900 mg of Ca2+ turns over approximately 12 times per day. Thus the glomerulus of the kidney filters ~10,000 mg of Ca2+ per day, but the renal tubular reabsorption of this ion is so efficient that under normal circumstances only ~200 mg of Ca2+ appears in the urine. In the event of hypercalcemia, the urinary excretion of Ca2+ rises in a compensatory fashion; however, it rarely exceeds a value of 400–600 mg/day. The renal tubular reabsorption of Ca2+ is stimulated by the separate actions of PTH and 1α,25(OH)2D3 in the distal nephron of the kidney. Also, depending on the ambient temperature, an additional 50–200 mg of Ca2+ may be lost per day through the skin via sweating.

The dynamics of phosphate metabolism are not particularly different from those of calcium. Under normal circumstances, approximately one-third of phosphate in the diet is absorbed by the intestine. Absorption of phosphate is interrelated in a complex fashion with the presence of Ca2+ and can be stimulated by a low-calcium diet and also by 1α,25(OH)2D3. Phosphate in the body is also partitioned among three major pools: the kidney ultrafiltrate, the readily exchangeable fraction of bone, and the intracellular compartments in the various soft tissues.

The major excretory route for phosphate (Figure 1) is through the kidney. The handling of phosphate by the kidney is determined by the rates of glomerular filtration, tubular reabsorption, and possibly tubular secretion. Every day the kidney glomerulus filters some 6000 10,000 mg of phosphorus. A normal 70 kg person, given a diet containing 900 mg of phosphorus, excretes ~600 mg/ day in the urine.

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مواضيع ذات صلة

Leukotrienes in Human Disease

Prostaglandins and Cancer

Sanger Was the First to Determine the Sequence of a Polypeptide

The α-R Groups Determine the Properties of Amino Acids

Properties of the Functional Groups of Amino Acids

Examples of Biological Actions of Prostaglandins

Cyclooxygenase Inhibitors

Prostaglandin H Synthase/ Cyclooxygenase

Phospholipase A2

Overview of Eicosanoid Synthesis

Structure and Nomenclature of Eicosanoids

Water is an Excellent Nucleophile