The effect of chronic hypotonic volume expansion on the renal regulation of acid-base equilibrium

Abstract

A B S T R A C T Balance studies have been carried out to evaluate the influence of vasopressin-induced volume expansion on acid-base equilibrium in normal dogs and in dogs with steady-state metabolic acidosis induced by the administration of 5-7 mmoles/kg per day of hydrochloric acid.Hypotonic expansion in dogs with metabolic acidosis (mean plasma bicarbonate concentration 14 mEq/liter) produced a marked increase in renal acid excretion that restored plasma bicarbonate concentration to normal (20-21 mEq/liter) despite continued ingestion of acid.When water was restricted during the vasopressin period, and fluid retention thus prevented, no increase in acid excretion or plasma bicarbonate concentration occurred. From these findings we conclude that hypotonic expansion is a potent stimulus to renal hydrogen ion secretion and greatly facilitates the renal removal of an acid load.Normal dogs subjected to expansion demonstrated no change in net acid excretion or in plasma bicarbonate concentration even in the face of a marked diuresis of sodium and chloride and a reduction in plasma sodium concentration to approximately 110 mEq/liter. The animals did, however, regularly lose potassium, a finding that clearly indicates an acceleration of distal sodiumcation exchange. On the basis of these observations, and the findings in the expanded acidotic dogs, we suggest that in the expanded normal dogs acceleration of sodium-hydrogen exchange was responsible for preventing a bicarbonate diuresis and for stabilizing plasma bicarbonate concentration.These studies clearly demonstrate that chronic hypotonic expansion exerts a major influence on the renal A preliminary report of this work was published in abstract form in: 1971. J. Clin. Invest. 50: 62 a. (Abstr.)

The critical role of the adrenal gland in the renal regulation of acid-base equilibrium during chronic hypotonic expansion. Evidence that chronic hyponatremia is a potent stimulus to aldosterone secretion.

“…Previous studies from this laboratory have indicated that the renal response to HVE causes a striking increase in plasma bicarbonate concentration in animals with chronic HCI acidosis and prevents the anticipated fall in plasma bicarbonate concentration in normal animals (1). In the present study, these effects on acid-base equilibrium were found to be associated temporally with the rise in aldosterone levels.…”

“…2. Note that the data for intact animals used in this figure include not only observations from the present study but also from a previous study of six intact animals treated identically (1). Fig.…”

“…The mean of the values obtained on the 4th and 5th days of vasopressin administration (ADH days 4 and 5) was selected for most comparisons because, as previously noted (1) (1) are included with the present observations. Note that the response of plasma osmolality was similar in both the intact and ADX dogs, but that the response of plasma bicarbonate was markedly different.…”

“…Chronic hypotonic expansion of the body fluids, induced by the prolonged administration of vasopressin and water, produces a marked enhancement of distal hydrogen ion secretion in dogs with HClinduced acidosis (1). The restulting increase in renal acid excretion is enough to restore plasma bicarbonate concentration completely to nonral, even in the face of the continued daily administration of a large acid load.…”

Hyposmolality stimulates apical membrane Na+/H+ exchange and HCO3– absorption in renal thick ascending limb

“…It is likely, therefore, that the transport effects and signaling pathways induced by hyposmolality in the present study are relevant to the response of the MTAL to physiologic decreases in extracellular osmolality in vivo, irrespective of whether those decreases achieve hyposmotic levels (26,41,50). Stimulation of apical membrane Na + /H + exchange activity and HCO 3 -absorption in the MTAL by a fall in osmolality could contribute to the urine acidifying effects of loop-acting diuretics (51,52) and to the increase in urinary net acid excretion that maintains constant the plasma HCO 3 -concentration during hypotonic volume expansion (53). Our findings have additional implications for regulation of sodium balance if hyposmolality stimulates apical Na + /H + exchange activity in other nephron segments such as the proximal tubule, where NHE3 mediates NaCl absorption as well as NaHCO 3 absorption (17,19).…”