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INTRODUCTION

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ACTH Adrenocorticotropin hormone
ADHR Autosomal dominant hypophosphatemic rickets
AHO Albright hereditary osteodystrophy
AIRE Autoimmune regulator
BMD Bone mineral density
CaSR Extracellular calcium-sensing receptor
CGRP Calcitonin gene–related peptide
DBP Vitamin D–binding protein
DXA Dual-energy x-ray absorptiometry
FGF23 Fibroblast-derived growth factor 23
FHH Familial hypocalciuric hypercalcemia
GALNT3 UDP-N-acetyl-α-D-galactosamine transferase
HPT-JT Hyperparathyroidism-jaw tumor
HT Hormone therapy
ICMA Immunochemiluminescent assay
IFN Interferon
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 Pseudopseudohypoparathyroidism
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
RAR Retinoic acid receptor
RBP Retinol-binding protein
RET Rearranged during transfection
RXR Retinoid X receptor
SERMs Selective estrogen response modulators
sFRP Secreted frizzled related protein
TNF Tumor necrosis factor
TPN Total 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

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CELLULAR AND EXTRACELLULAR CALCIUM METABOLISM

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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.

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It is the concentration of ionized calcium ([Ca2+]) 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 whole blood, in which citrate is used as an anticoagulant, can reduce the ionized [Ca2+] enough to produce tetany. In addition, because calcium and ...

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