1. Total body, intracellular, and extracellular electrolyte and acid-base changes were studied following sodium nitrate-induced potassium and chloride depletion and subsequent selective chloride repletion.2. It was found that potassium and chloride depletion was associated with markedly decreased extracellular Na, K, CI and water content. Intracellular Na increased, intracellular K decreased and there was a large transcellular redistribution of acid, i.e. extracellular alkalosis and intracellular acidosis ensued.3. Selective chloride repletion was associated with return of extracellular pH towards normal. Extracellular K and intracellular parameters showed very little change. Further chloride administration was followed by extracellular acidosis, but extracellular K remained low.4. There was close relationship between extracellular chloride and hydrogen ion concentrations ([CI-]e and [H+]e) and extracellular potassium and intracellular hydrogen ion ([K +]e and [H+]i) but not between any of the other parameters. The close relationship between [H+]e and [CI-]e may be explained by the chemical relationship between [H+]e, Peo 2 , and [HC0 3 -]e and empirical relationships between [Cl-]e and [HC0 3-]e, and Pco, and [HC0 3 -leoThe role of potassium and chloride in the control of extracellular pH (pH e ) and intracellular pH (pH j) is unsettled.Potassium and chloride may be varied independently of each other by initial depletion of potassium and chloride stores with repeated infusions of sodium nitrate and then selective replenishment of chloride. However, analysis of results is clouded by secondary changes of body fluid compartments. When these selective electrolyte depletions are combined with measurement of pl-l, and pHi as well as body fluid constituents, quantitative interrelationships between electrolytes and acid-base parameters may be explored.It was found that the extracellular alkalosis observed after nitrate infusion was due in part to transcellular acid shifts and development of intracellular acidosis, in part to extracellular fluid (ECF) contraction, and in small part to other causes. Intracellular acidosis persisted but extracellular hydrogen ion concentration [H+]e returned to normal when chloride was repleted and potassium was not replaced, suggesting that to a large extent [H+]e is a function of extracellular chloride concentration [Cl"je and intracellular hydrogen ion concentration ([H+]i) of intracellular potassium concentration ([K +]i). The failure of others to find intracellular acidosis during potassium depletion will be discussed.
METHODSThirteen trained, unanaesthetized dogs of both sexes ranging from 12·5 to 27·5 kg were studied in twenty-two experiments. The animals were maintained throughout the experiment on a diet low in Na, K, and CI by feeding 7 g kg-1 day " ! of ground horsemeat which had been washed thoroughly with distilled water and then oven-dried, removing virtually all the sodium, potassium and chloride (Na 26·3 ±2'3, K 45·8 ± 3'5, CII9'0±0'9 J.lEq/g dry weight (average of five det...