The Existence of Ammonia in Blood in Vivo With Observations on the Significance of the Nh4+–nh3 System *

Abstract

The development of refined methods for determination of blood ammonia in the past 50 years has resulted in a gradual lowering of the reported concentrations in the peripheral venous blood of normal man (1). After extensive work with a microdiffusion technique, Conway and Cooke concluded that the normal in vivo peripheral venous level of the blood ammonia nitrogen in man was operationally zero, but that rapid liberation of ammonia from certain precursors occurred after shedding to produce in vitro values of about 35 Amoles ammonia-nitrogen (NH3-N) per L blood (2). Identical conclusions were reached by Koprowski and Uninski in their work on dog blood (3), using Conway's method. The results of more recent investigations using different techniques (4-7) have indicated that peripheral venous blood does contain significant amounts of ammonia in vivo. This conflict has not been resolved despite frequent use of the Conway method in many investigations of human ammonia metabolism in the past decade.The present experiments were stimulated by the observation that dogs receiving intravenous infusions of ammonium salts excreted measurable amounts of NH8 gas in expired air (8). This ammonia was presumably derived from the dissolved NH. gas which must exist in equilibrium

The Pnh3 of Renal Tubular Cells*

“…Use of either expression implies that only the free base diffuses in appreciable amounts across cell membranes and that diffusion, not active secretion, accounts for the movement of ammonia into both urine and peritubular blood. Values of PNH3 that we have observed are of the same order of magnitude as those observed by Bromberg, Robin, and Forkner (13). As a consequence of our studies on the intravenous infusion of ammonium lactate in dogs we have reached the following conclusions.…”

Renal Ammonia Balance. A Kinetic Treatment

“…The (ammonia) of whole blood has therefore been calculated by multiplying all values for theoretical plasma (ammonia) by a factor representing the ratio of venous whole blood to plasma (ammonia). The value 1.4 has been assigned to this ratio; this is the value furnished in wrhat appears to be the most careful study reported (48), represents the mean o f values arrived at in four recent studies (28,(48)(49)(50), and is in accord with our own observations. Plasma (ammonia) was taken as 0.93 X plasma water (ammonia) (51).…”

The Effect of Induced Hyperammonemia on Renal Ammonia Metabolism*†

“…Ammonia in blood even during extreme hyperammonemia exists primarily in the NH4+ form. The concentration of NH3 represents only a minute fraction of the total blood ammonia concentration (22), and in the present study is obviously of insufficient magnitude to explain the alterations in renal ammonia balance across the renal circulation during ammonium lactate infusion. It would seem likely, therefore, that the renal tubular cells removed significant quantities of NH4+ from the blood during these experiments.…”