Dietary NaCl determines severity of potassium depletion–induced metabolic alkalosis

Abstract

It is uncertain whether, in humans, potassium depletion can cause or sustain metabolic alkalosis of clinically important degree in the absence of coexisting known alkalosis-producing conditions. Previously we found, in normal humans ingesting abundant NaCl, that dietary K+ depletion alone can induce and sustain a small decrease in blood acidity and increase in plasma bicarbonate concentration; we hypothesized that more severe alkalosis was prevented by mitigating mechanisms initiated by renal retention of dietary NaCl that was induced by K+ depletion. To ascertain the acid-base response to dietary K+ depletion under conditions in which the availability of NaCl for retention is greatly limited, in the present study of six normal men we restricted dietary K+ as in the previous study except that intake of NaCl was maintained low (2 to 7 mEq/day, Low NaCl Group) instead of high (126 mEq/day, High NaCl Group). Plasma acid-base composition and renal net-acid excretion (NAE) did not differ significantly between groups during the control period. In the steady state of K+ depletion (days 11 to 15 of K+ restriction), neither plasma K+ concentration (2.9 +/- 0.9 mEq/liter vs. 3.0 +/- 0.1 mEq/liter) nor cumulative K+ deficit (399 +/- 59 mEq vs. 466 +/- 48 mEq) differed significantly between groups. During K+ restriction, persisting metabolic alkalosis developed in both groups, which was more severe in the Low NaCl Group: increment in [HCO3-]p, 7.5 +/- 1.0 mEq/liter versus 2.0 +/- 0.3 mEq/liter, P less than 0.001; decrement in [H+]p, 5.5 +/- 0.6 nEq/liter versus 2.9 +/- 0.4 nEq/liter, P less than 0.003. A significantly more severe alkalosis in the Low NaCl Group was evident at all degrees of K+ deficiency achieved during the course of the 15 days of K+ restriction, and the severity of alkalosis in the Low NaCl Group correlated with the degree of K+ deficiency. During the generation of alkalosis (days 1 to 7 of K+ restriction), NAE increased in the Low NaCl Group whereas it decreased in the High NaCl Group. During the maintenance of alkalosis (days 11 to 15), NAE stabilized in both groups after it returned to values approximating the control values. In both groups, urine Cl- excretion decreased during K+ restriction even though Cl- intake had not been changed, with the result that body Cl- content increased negligibly in the Low NaCl Group (28 +/- 6 mEq) and substantially in the High NaCl Group (355 +/- 64 mEq).(ABSTRACT TRUNCATED AT 400 WORDS)

Potassium depletion increases luminal Na+/H+ exchange and basolateral Na+:CO3=:HCO3- cotransport in rat renal cortex.

“…of 278 nmol/min/mg protein in KD vs. 177 nmol/min/mg protein in C. Influx of 1 mM 22Na' at 5 s (pH. 7.5, pH, 6.0) into BBM vesicles was 34% higher in the KD group compared to C with no difference in equilibrium uptake. The increment in Na+ influx in the KD group was amiloride sensitive, suggesting that Na+/H+ exchange was responsible for the observed differences.…”

“…KD rats gained less weight than C but had higher renal cortical weight. Influx of 1 mM 22Na' at 5 s (pHi 7.5, pHi 6.0, 10% C02, 90% N2) into BLM vesicles was 44% higher in the KD group compared to C with no difference in equilibrium uptake. The increment in Na+ influx in the KD group was DIDS sensitive, suggesting that Na+:CO3 :HCO3 cotransport accounted for the observed differences.…”

“…This adaptive change in HCOj reabsorption has been invoked as a possible mechanism involved in the pathogenesis of systemic metabolic alkalosis in disorders associated with potassium depletion (5). Selective potassium deficiency has been shown to cause metabolic alkalosis in humans (6,7) and in most studies in rats (1-4, 8, 9). In experiments in dogs (10)(11)(12) and rabbits (13), however, potassium deficiency resulted in metabolic acidosis.…”

Adenosine triphosphate citrate lyase mediates hypocitraturia in rats.

“…To address whether intra-or extracellular pH is the key regulator of ATP citrate lyase activity, we examined the effect of chronic K ϩ -deficiency on ATP citrate lyase activity. Rats fed a control diet were compared with rats pair fed a K ϩ -free diet for 7 d. A high sodium, K ϩ -free diet was used to prevent the development of metabolic alkalosis (29). As shown in Table I, rats fed a K ϩ -free diet developed hypokalemia.…”

Treatment of Severe Metabolic Alkalosis with Continuous Renal Replacement Therapy

“…1 The treatment of metabolic alkalosis should aim to reduce the ongoing acid losses from the stomach and reverse the factors that impair renal bicarbonate excretion, namely hypochloremia and hypokalemia. [2][3][4] Gastric acid secretion can be reduced in ZES by proton pump inhibitors (PPI), which inhibit the hydrogen/potassium ATPase on the luminal surface of parietal cells. 5 Chloride repletion with an appropriate cation is necessary to reverse metabolic alkalosis.…”