Studies on the source and significance of blood ammonia. 3. Effects of altering blood ammonia concentration and hematocrit on the distribution of ammonia.

Approximately three fourths of the ammonia content of whole blood is contained in the red cells and one fourth in the plasma of normal subjects. As shown previously, the ammoniat concentration of erythrocytes is normally about three times that of plasma.' Significant differences from the normal distribution occur, however, in patients with anemia or elevated blood ammonia levels.! Elevations in blood ammonia concentration have been found to be associated with increased ammonia levels of both plasma and erythrocytes. These increments were, however, disproportionately large in plasma and smaller than expected in red cells. The ammonia concentration of erythrocytes often fell to twice that of plasma and in that situation, approximately one half of the ammonia content of whole blood was contained in erythrocytes and the other half in plasma. Two hypotheses were considered to explain this phenomenon, which was observed in both spontaneous and induced elevations of blood ammonia concentration. First, the relatively large increase in plasma ammonia concentration may have reflected the central position of plasma in the absorption, transport, and removal of ammonia."'2' This hypothesis was supported by the finding of disproportionately high ammonia concentrations in the plasma of arterial blood compared to venous blood.' Acceptance of this hypothesis, however, implies that the equilibration of ammonia between plasma and red cells is relatively slow. The alternative explanation assumes that the increment in ammonia is distributed uniformly between plasma and erythrocytes, i.e. independently of the pre-existing erythrocyte :plasma ratio. In anemic patients the ammonia concentration of both plasma and erythrocytes was found to be higher than in non-anemic subjects, and the in-