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  • ACTH Adrenocorticotropin
  • ADHR Autosomal dominant hypophosphatemic rickets
  • AHO Albright hereditary osteodystrophy
  • AIRE Autoimmune regulator
  • BMD Bone mineral density
  • CaSR Extracellular calcium-sensing receptor
  • CGRPCalcitonin gene–related peptide
  • DBP Vitamin D–binding protein
  • DXA Dual-energy x-ray absorptiometry
  • FBHH Familial benign hypocalciuric hypercalcemia
  • FGF23 Fibroblast-derived growth factor 23
  • GALNT3 UDP-N-acetyl-α-D-galactosamine transferase
  • HPT-JT Hyperparathyroidism-jaw tumor
  • HTHormone therapy
  • ICMA Immunochemiluminescent assay
  • IFNInterferon
  • IGF Insulin-like growth factor
  • IL Interleukin
  • IP3 Inositol 1,4,5-triphosphate
  • IRMA Immunoradiometric assay
  • LDL Low-density lipoprotein
  • MCT Medullary carcinoma of thyroid
  • MEN Multiple endocrine neoplasia
  • MEPE Matrix extracellular phosphoglycoprotein
  • NALP5 NACHT leucine-rich-repeat protein 5
  • OPG Osteoprotegerin
  • PHP Pseudohypoparathyroidism
  • PIP2 Phosphatidylinositol 4,5-bisphosphate
  • PPHP Pseudo pseudohypoparathyroidism
  • PTH Parathyroid hormone
  • PTHrP Parathyroid hormone–related protein
  • RANK Receptor activator of nuclear factor kappa B
  • RANKL Receptor activator of nuclear factor kappa-B ligand
  • RARRetinoic acid receptor
  • RBP Retinol-binding protein
  • RXR Retinoid X receptor
  • SERMs Selective estrogen response modulators
  • sFRP Secreted frizzled related protein
  • TNF Tumor necrosis factor
  • TPNTotal parenteral nutrition
  • TRP Tubular reabsorption of phosphate
  • VDR Vitamin D receptor
  • VDRE Vitamin D response element
  • VIP Vasoactive intestinal polypeptide
  • WHI Women's Health Initiative
  • WHO World Health Organization
  • XLH X-linked hypophosphatemia

The calcium ion plays a critical role in intracellular and extracellular events in human physiology. Extracellular calcium levels in humans are tightly regulated within a narrow physiologic range to provide for proper functioning of many tissues: excitation-contraction coupling in the heart and other muscles, synaptic transmission and other functions of the nervous system, platelet aggregation, coagulation, and secretion of hormones and other regulators by exocytosis. The level of intracellular calcium is also tightly controlled, at levels about 10,000-fold lower than extracellular calcium, in order for calcium to serve as an intracellular second messenger in the regulation of cell division, muscle contractility, cell motility, membrane trafficking, and secretion.

It is the concentration of ionized calcium ([Ca0<+]) that is regulated in the extracellular fluid. The ionized calcium concentration averages 1.25 ± 0.07 mmol/L (Table 8–1). However, only about 50% of the total calcium in serum and other extracellular fluids is present in the ionized form. The remainder is bound to albumin (about 40%) or complexed with anions such as phosphate and citrate (about 10%). The protein-bound and complexed fractions of serum calcium are metabolically inert and are not regulated by hormones; only the ionized [Ca2+] serves a regulatory role, and only this fraction is itself regulated by the calciotropic hormones parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D [1,25(OH)2D]. Large increases in the serum concentrations of phosphate or citrate can, however, by mass action, markedly increase the complexed fraction of calcium. For example, massive transfusions of blood, in which citrate is used as an anticoagulant, can reduce the ionized [Ca2+] enough to produce tetany. In addition, because calcium and phosphate circulate at concentrations close to saturation, a substantial rise in the serum concentration of either calcium or phosphate can lead to the precipitation ...

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