On the mechanism of lithium-induced renal tubular acidosis: Studies in the turtle bladder

Abstract

The mechanism whereby lithium impairs urinary acidification was investigated in vitro with the bladder of the fresh water turtle. The effect of lithium was compared to that of choline or cesium. In the presence of 1% carbon dioxide, lithium (40 mM in the mucosa) failed to alter hydrogen ion secretion. Lithium also caused a significant decrease in sodium transport and in potential difference. Lithium failed to increase the passive loss of hydrogen ions from the mucosal solution, indicating that it does not affect the permeability of the mucosa to hydrogen ions. Bicarbonate secretion also was unchanged in lithium-treated hemibladders. Under open-circuit conditions, lithium caused a significant decrease in potential difference and, hence, caused a significant decrease in hydrogen ion secretion. Restoration of the potential difference, in the presence of lithium, to control levels caused a return of hydrogen ion secretion to the original value. These data demonstrate that in the turtle baldder lithium inhibits hydrogen ion secretion solely by reducing the potential difference and suggest that in vivo lithium causes an acidification defect not by directly inhibiting the hydrogen ion pump or causing a hydrogen ion backleak but by inhibiting sodium transport, thereby decreasing the favorable electric gradient for hydrogen ion secretion.