Experimental Potassium Depletion in Normal Human Subjects. Ii. Renal and Hormonal Factors in the Development of Extracellular Alkalosis During Depletion*

Neurologic findings characteristic of the impending hepatic coma syndrome occur in some cirrhotic patients treated with diuretic agents that may induce potassium losses (1-5). Even when diuretic agents are not employed, hypokalemia may be associated with this syndrome (6-8). Patients demonstrating these signs often improve after treatment with potassium salts. This result of therapy might indicate that potassium deficiency per se is a pathogenetic factor in the impending hepatic coma syndrome (9). Because of the extensive evidence relating abnormalities in nitrogen metabolism to hepatic coma (10), however, it seemed possible that some derangement of nitrogen metabolism might be associated with potassium deficiency.This hypothesis, relating potassium deficiency indirectly to the hepatic coma syndrome by an influence this cation has on ammonium metabolism, provided the rationale for undertaking this investigation. The relation of potassium to ammonium metabolism was studied in patients with cirrhosis of the liver and ascites rendered acutely potassium deficient by a diuretic regimen. The results of these studies demonstrate that metabolism of ammonium by the kidney is altered in potassium-deficient patients and that significant quantities of ammonium may be delivered to the cir-* A preliminary report of this investigation was included in the proceedings of the American Association for Study of Liver Disease, Chicago, 1959 (Gastroenterology 1960, 38, 803).

Section: Discussionsupporting

confidence: 58%

Relation of Acute Potassium Depletion to Renal Ammonium Metabolism in Patients With Cirrhosis*

Baertl¹,

Sancetta²,

Gabuzda³

1963

“…Some of the subjects represented by 0 were mildly alkalotic and were excreting significant amounts of urinary bicarbonate (27) ; the subj ects represented by + were moderately alkalotic and were excreting more than 50 mEq of urinary bicarbonate daily (22) ; the subjects represented by X were given large amounts of desoxycorticosterone after hypokalemia supervened (27 (14,36,37). Such an impairment could differ from that in the presently reported patients only in degree.…”

Section: Methodsmentioning

confidence: 62%

“…servation of potassium, hypokalemia may occur with The results of the present studies indicate that both in (21)(22)(23)(24)(25)(26)(27). Some of the subjects represented by 0 were mildly alkalotic and were excreting significant amounts of urinary bicarbonate (27) ; the subj ects represented by + were moderately alkalotic and were excreting more than 50 mEq of urinary bicarbonate daily (22) ; the subjects represented by X were given large amounts of desoxycorticosterone after hypokalemia supervened (27 (14,36,37).…”

Section: Methodsmentioning

confidence: 78%

“…When dietary potassium is restricted in most normal subjects, the occurrence of hypokalemia is less rapid, despite relatively greater cumulative urinary losses of potassium (21)(22)(23)(24)(25)(26). But in normal subjects, in contrast to the patients studied with RTA, urinary excretion of potassium decreases to less than 40 mEq/day when hypokalemia occurs, even when it occurs rapidly and despite relatively modest negative potassium balance (27). Moreover, when serum potassium concentration is rapidly reduced experimentally by hemodialysis and changes in arterial pH and bicarbonate concentration are prevented, the rate of excretion of urinary potassium varies directly with the serum potassium concentration (28).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Renal potassium wasting in renal tubular acidosis (RTA)

Sebastián¹,

McSherry²,

Morris³

1971

127

A B S T R A C T In two patients with classic renal tubular acidosis (RTA) and in two patients with RTA associated with the Fanconi syndrome, renal potassium wasting persisted despite sustained correction of acidosis:(a) during moderate degrees of hypokalemia, daily urinary excretion of potassium exceeded 80 mEq in each patient; (b) during more severe degrees of hypokalemia, daily urinary excretion of potassium exceeded 40 mEq in two patients and 100 mEq in another. These urinary excretion rates of potassium are more than twice those observed in potassium-depleted normal subjects with even minimal degrees of hypokalemia. The persistence of renal potassium wasting may have resulted in part from hyperaldosteronism, since urinary aldosterone was frankly increased in two patients and was probably abnormally high in the others relative to the degree of their potassium depletion. The hyperaldosteronism persisted despite sustained correction of acidosis, a normal sodium intake, and no reduction in measured plasma volume, and was not associated with hypertension; its cause was not defined. In the two patients with classic RTA, neither renal potassium wasting nor hyperaldosteronism could be explained as a consequence of a gradient restriction on renal H' -Na' exchange because the urinary pH remained greater than, or approximately equal to, the normal arterial pH or considerably greater than the minimal urinary pH attained during acidosis. The findings provide no support for the traditional view that renal potassium wasting in either classic RTA or RTA

“…Most investigators agree, nevertheless, that both hydrogen ion secretion and renal ammonia production are regulated by intracellular pH. Both, for example, are increased in potassium deficiency despite a concomitant metabolic alkalosis (35). Also glutamine oxidation and presumably ammonia production in renal cortical slices and mitochondria is directly related to changes in pH (36).…”

Section: Discussionmentioning

confidence: 99%

Effect of volume expansion on renal citrate and ammonia metabolism in KCl-deficient rats.

Adler¹,

Anderson²,

Fraley³

1975

A B S T R A C T When rats with desoxycorticosterone acetate (DOCA)-induced potassium chloride deficiency are given sodium chloride there is simultaneously a partial correction of metabolic alkalosis and a marked reduction in urinary citrate excretion and renal citrate content. To examine DOCA's role in this phenomenon and to determine how sodium chloride alters renal metabolism, rats were made KC1 deficient using furosemide and a KCl-deficient diet. Renal citrate and ammonia metabolism were then studied after chronic oral sodium chloride administration or acute volume expansion with isotonic mannitol. Although both maneuvers partially corrected metabolic alkalosis, sodium chloride raised serum chloride concentration while mannitol significantly decreased it. Urinary citrate excretion decreased to 10% of control in rats given NaCl and to 50% of control in rats infused with mannitol. The filtered load of citrate was constant or increased indicating increased tubular citrate reabsorption. Renal cortical citrate content also decreased approximately 50%. Renal cortical slices from KCl-deficient rats incubated in low or normal chloride media produced equal amounts of "CO2 from [1,5-"4C]citrate.In addition, urinary ammonia excretion increased by over 300% in both groups. This occurred in the mannitol group despite increased urinary pH and flow rate indicating a rise in renal ammonia production.It seems that neither DOCA nor an increase in serum chloride concentration explains the experimental results. Rather, it appears that volume expansion is responsible for increased renal tubular citrate reabsorption and renal ammonia production. As these renal metabolic This work was previously reported in abstract form: Adler, S., B. Zett, B. Anderson, and D. Fraley. 1974. Role of chloride and volume expansion in regulating renal citrate metabolism. Clin. Res. 22: 654a.