Roscoe J M, Goldstein M B, Halperin M L, Wilson D R, Stinebaugh B J
Kidney Int. 1976 Apr;9(4):344-50. doi: 10.1038/ki.1976.40.
The purpose of this study was to clarify the means by which lithium induced a disorder of urine acidification. Rats infused with hydrochloric acid (1 mEq/kg) developed acute metabolic acidosis (blood Ph = 7.32; bicarbonate, 18 mEq/liter) with a urine pH of approximately 5.85. The addition of lithium chloride (4 mEq/kg i.p) caused an increase in the urine pH (6.38) and a further decrease in blood bicarbonate (11.0 mEq/liter). During bicarbonate loading, lithium caused the urine PCO2 to fall significantly (urine minus blood PCO2 decreased from 25.3 +/-2.8 To 14.4 +/- 2.3 mm Hg) These changes were not seen following equimolar i.p. administration of sodium chloride. Similarly, lithium administration depressed bicarbonate reabsorption by 11.1% (from 30.6 to 27.2muEq/ml of GFR) during alkali infusion, while saline caused only a 5% decrease (30.0 to 28.5muEq/ml of GFR). The combination of an increase in urine PCO2 in alkaline urine indicates that lithium produced a defect in distal nephron hydrogen ion secretion. The fall in bicarbonate reabsorption following lithium administration oculd be due to a mild hydrogen ion secretory defect located in the proximal tubule or a severe defect in the distal nephron.
本研究的目的是阐明锂导致尿酸化紊乱的机制。给大鼠输注盐酸（1 mEq/kg）会引发急性代谢性酸中毒（血液pH = 7.32；碳酸氢盐，18 mEq/升），尿液pH约为5.85。添加氯化锂（4 mEq/kg腹腔注射）会使尿液pH升高（6.38），血液碳酸氢盐进一步降低（11.0 mEq/升）。在碳酸氢盐负荷期间，锂使尿液PCO2显著下降（尿液与血液PCO2差值从25.3±2.8降至14.4±2.3 mmHg）。等摩尔腹腔注射氯化钠后未观察到这些变化。同样，在输注碱液期间，锂使碳酸氢盐重吸收降低11.1%（从30.6降至27.2μEq/ml肾小球滤过率），而生理盐水仅使其降低5%（从30.0降至28.5μEq/ml肾小球滤过率）。碱性尿液中尿液PCO2升高表明锂导致远端肾单位氢离子分泌存在缺陷。锂给药后碳酸氢盐重吸收下降可能是由于近端小管存在轻度氢离子分泌缺陷或远端肾单位存在严重缺陷。
