Figure 312

Mechanisms of hypokalemia in Bartter's syndrome and Gitelman's syndrome. A, A defective Na+-K+-2Cl- cotransporter in the thick ascending limb (TAL) of Henle's loop can account for virtually all features of Bartter's syndrome. Since approximately 30% of filtered sodium is reabsorbed by this segment of the nephron, defective sodium reabsorption results in salt wasting and elevated renin and aldosterone levels. The hyperaldostero-nism and increased distal sodium delivery account for the characteristic hypokalemic metabolic alkalosis. Moreover, impaired sodium reabsorption in the TAL results in the hypercalciuria seen in these patients, as approximately 25% of filtered calcium is reabsorbed in this segment in a process coupled to sodium reabsorption. Since potassium levels in the TAL are much lower than levels of sodium or chloride, luminal potassium concentrations are rate limiting for Na+-K+-2Cl- co-transporter activity. Defects in ATP-sensitive potassium channels would be predicted to alter potassium recycling and diminish Na+-K+-2Cl- cotrans-porter activity. Recently, mutations in the gene that encodes for the Na+-K+-2Cl-cotransporter and the ATP-sensitive potassium channel have been described in kindreds with Bartter's syndrome. Because loop diuretics interfere with the Na+-K+-2Cl-cotransporter, surrepititious diuretic abusers have a clinical presentation that is virtually indistinguishable from that of Bartter's syndrome. B, Gitelman's syndrome, which typically presents later in life and is associated with hypomagnesemia and hypocalci-uria, is due to a defect in the gene encoding for the thiazide-sensitive Na+-Cl- cotrans-porter. The mild volume depletion results in more avid sodium and calcium reabsorption by the proximal nephrons.

0 0

Post a comment