Pathophysiology of red cell volume.

In the current work, we review three situations where red cell volume changes are important. Red cell apoptosis (eryptosis) accounts for the removal of ageing and damaged erythrocytes from the circulation by macrophages. Amongst other cellular responses, eryptosis is associated with net cytosolic KCl loss and concomitant cell shrinkage. KCl efflux is mediated by activation of Ca(2+)-activated K(+) (Gardos) channels, permitting downhill movement of K(+) and electrically obliged Cl(-) through, as yet, incompletely described pathways. Red cells from patients suffering from sickle cell disease demonstrate progressive dehydration. Osmolyte loss is accounted for by the activation of two separate pathways. KCl cotransport, normally quiescent in red cells from HbA individuals, is activated under deoxygenated conditions and mediates net KCl efflux. Furthermore, intracellular Ca(2+) is elevated, probably as a result of Ca(2+) influx through a deoxygenation induced non-selective cation pathway termed P(sickle). This results in Gardos channel activation coupled indirectly with Cl(-) loss. Finally, a number of red cell stomatocytoses have been described where alterations to erythrocyte volume are the result of increased membrane cation permeability, in particular to Na(+) and K(+). The emerging significance of non-selective cation pathways is common to each of these conditions, and, although differences exist between their properties, particularly with regard to activation and ion selectivity, it is conceivable that they represent activation of closely related pathways. The recent finding that many hereditary stomatocytoses are caused by mutations to band 3 (AE-1) raises the possibility that modifications to this transporter could account for altered cation fluxes under different conditions.