Bartter's syndrome: a unifying hypothesis

Abstract

The most proximate defect responsible for the pathogenesis of Bartter's syndrome remains uncertain. Although an abnormality in chloride reabsorption in the thick ascending limb of Henle has been postulated, renal clearance studies performed during oral water loading failed to disclose a reduction in fractional chloride reabsorption. We alternatively postulate that the underlying abnormality may reside in a generalized increase in cell sodium permeability. Elevated levels of cell sodium may secondarily stimulate Na-K-ATPase activity. In the cells of the distal nephron, stimulated Na-K-ATPase would lead to enhanced potassium secretion into the tubular fluid producing the characteristic potassium depletion. In addition, increased cell sodium influx may stimulate a sodium-calcium exchanger. If this process exists in vascular smooth muscle, it may result in reduction of cytosolic calcium activity. This effect and/or chronic potassium depletion may mediate the reduced vascular reactivity characteristic of this syndrome.