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

Abstract

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).

Effect of bath and luminal potassium concentration on ammonia production and secretion by mouse proximal tubules perfused in vitro.

“…Although clinical disorders associated with hyperkalemia (19) or hypokalemia (20) may be associated with altered rates of potassium excretion, they generally reflect more chronic changes in plasma potassium concentration and total potassium balance. The results ofthe present studies clearly demonstrate that acute elevation in ambient potassium concentration to levels that may occur in vivo suppresses total ammonia production rates in the proximal tubule perfused in vitro in the presence or absence of glutamine in the luminal perfusion solution, while an acute reduction of the ambient potassium concentration stimulates total ammonia production rates in the absence of luminal L-glutamine.…”

Renal Adaptation to a High Potassium Intake

“…and measurements of renal blood flow during potassium adaptation have not been reported; a definitive conclusion must await further study. Although the renal slice data mitigate against a decrease in renal ammonia production, it is still a tempting speculation in view of the well-documented increase in renal ammonia production that accompanies potassium depletion (4,(21)(22)(23)(24)(25)(26).…”

The effect of uncomplicated potassium depletion on urine acidification

“…These observations are all consistent with an increased rate of ammonia production. Conflict exists regarding the glutaminase activity in the kidneys of potassium-depleted dogs (27,28); however, Gabuzda, Hall, Baertl, and Sancetta have shown by direct techniques in vivo that potassium depletion can increase renal ammonia production in normal dogs and also in humans with cirrhosis (28,29). No direct measurements of renal ammonia production in normal humans have been reported to date.…”