Mechanism of organ dysfunction in phosphate depletion: a critical role for a rise in cytosolic calcium.
Phosphate depletion (PD) is associated with multiorgan dysfunction. It has been proposed that this phenomenon is due to two metabolic derangements: (a) there is a reduction in ATP content of cells and hence reduced availability of energy-rich phosphate compounds, and (b) there is a decrease in 2,3-diphosphoglycerate in red blood cells, a change that would increase the affinity of hemoglobin to oxygen resulting in tissue hypoxia. Recent studies have demonstrated that PD is associated with a significant elevation in basal levels of cytosolic calcium [Ca2+]i in many cells. This is due to an increased entry into and decreased extrusion of calcium out of cells. This rise in [Ca2+]i plays a major role in organ dysfunction in PD and in the genesis of decreased ATP content of cells.
Massry
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SG
Division of Nephrology, University of Southern California School of Medicine, Los Angeles 90033.
Fadda
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GZ
Perna
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Kiersztejn
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Smogorzewski
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D009102:Multiple Organ Failure / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*
D010710:Phosphates; D002118:Calcium