As bstract. To determine whether chloride-depletion metabolic alkalosis (CDA) can be corrected by provision of chloride without volume expansion or intranephronal redistribution of fluid reabsorption, CDA was produced in Sprague-Dawley rats by peritoneal dialysis against 0.15 M NaHCO3; controls (CON) were dialyzed against Ringer's bicarbonate. Animals were infused with isotonic solutions containing the same Cl and total CO2 (tCO2) concentrations as in postdialysis plasma at rates shown to be associated with slight but stable volume contraction. During the subsequent 6 h, serum Cl and tCO2 concentrations remained stable and normal in CON and corrected towards normal in CDA; urinary chloride excretion was less and bicarbonate excretion greater than those in CON during this period. Micropuncture and microinjection studies were performed in the 3rd h after dialysis. Plasma volumes determined by 1251-albumin were not different. Inulin clearance and fractional chloride excretion were lower (P < 0.05) in CDA. Superficial nephron glomerular filtration rate determined from distal puncture sites was lower (P < 0.02) in CDA (27.9±2.3 nl/min) compared with that in CON (37.9±2.6). segment was less (P < 0.01) in group CDA. Urinary recovery of 36C1 injected into the collecting duct segment was lower (P < 0.01) in CDA (CON 74±3; CDA 34±4%).These data show that CDA can be corrected by the provision of chloride without volume expansion or alterations in the intranephronal distribution of fluid reabsorption. Enhanced chloride reabsorption in the collecting duct segment, and possibly in the distal convoluted tubule, contributes importantly to this correction.

Volume expansion has been considered essential for the correction of chloride-depletion metabolic alkalosis (CDA). To examine the predictions of this hypothesis, rats dialyzed against 0.15 M NaHCO3 to produce CDA and controls, CON, dialyzed against Ringer-f1C03 were infused with either 6% albumin (VE) or 80 mM non-sodium chloride salts (CC) added to 5% dextrose (DX) and studied by micropuncture. CDA was maintained in rats infused with DX. VE expanded plasma volume (25%), maintained glomerular filtration rate (GFR), but did not correct CDA despite increased fractional delivery of total CO2 (tCO2) out of the proximal tubule (36±2%) as compared with VE/CON (24±4%; P < 0.05). In contrast, CC corrected CDA despite volume contraction (-16%) and lower GFR than CC/CON; proximal tCO2 delivery in CC/CDA (29±4%) did not differ from YE/CDA. CC was associated with an increment in tCO2 excretion. The data strongly suggest that maintenance and correction of CDA are primarily dependent upon total body chloride and its influences on intrarenal mechanisms and not on the demands of sodium or fluid homeostasis.

Abstract. We have recently described reduced superficial nephron glomerular filtration rate (SNGFR) in chloride-depletion alkalosis (CDA) without volume depletion. To elucidate the mechanism of this phenomenon, we studied three degrees of increasing severity of CDA (groups CDA-1, 2, and 3) produced by one or two peritoneal dialyzes against 0.15 M NaHCO3 and electrolyte infusions of different Cl and HCO3 content in Sprague-Dawley rats; control rats (CON) were dialyzed against and infused with Ringers-HCO3. Extracellular fluid (ECF) volume was assessed by blood pressure, hematocrit, plasma protein concentration, and '251-albumin space; none of these variables differed among the four groups. Micropuncture of the latest proximal and earliest distal convolutions was carried out. As CDA intensified from CON to CDA-3 (plasma tCO2 25±1 to 43±1 meq/L; P < 0.01), distally determined SNGFR declined progressively (40.9±1.7 to 28.3±1.8 nl/min; P < 0.01), while in early distal tubule fluid, flow rate (8.6±0.7 to 3.4±0.6 nl/min) and Cl concentration (36±2 to 19±3 meq/L) decreased and osmolality (110±5 to 208±12 mosmol/kg) increased (P < 0.01), and, in the loop segment, Cl reabsorption decreased progressively (2,009±112 to 765±128 peq/min; P < 0.01). In early distal tubule fluid, Cl concentration correlated positively This study has been published in abstract form in Clin.

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Correction of chloride-depletion alkalosis (CDA) may involve renal as well as extrarenal mechanisms. To determine the relative contribution of these mechanisms in a rat model of CDA produced by peritoneal dialysis (PD), we studied six groups of anesthetized Sprague-Dawley rats after PD. Groups II-IV and IIa were subjected to functional bilateral nephrectomy, and groups I and Ia were sham-operated. Groups I, Ia, II, and IIa were infused with isotonic fluid containing 70 mM Cl- and 40 mM HCO3-; the infusate in group III was 140 mM Cl- and in group IV, 70 mM neutral PO4 was substituted for Cl-. Groups I and Ia were infused at 0.5 ml . h-1 X 100 g body wt-1 and groups II, IIa, III, and IV at 0.25 ml . h-1 X 100 g-1. After 3 h of infusion, early partial correction with reciprocal changes in plasma Cl (+6.1 +/- 1.9 mmHg) and total CO2 (-6.0 +/- 0.8 meq/liter) occurred (P less than 0.01) only in group I. Hypokalemia (3.1 +/- 0.1 meq/liter) also occurred only in group I. The responses of groups Ia and IIa studied at 5 h were similar to those of groups I and II. These data suggest that the kidney, and not extrarenal mechanisms, is primarily responsible for the correction of CDA during infusion of chloride.