Studies on the origin and significance of blood ammonia. II. The distribution of ammonia in whole blood, plasma and erythrocytes of man.

Most investigators who have studied ammonia metabolism in liver disease have measured the concentration of ammoniat in whole blood.1'° Only a few authors have used the plasma ammonia concentration.ll" Recently, several cation exchange techniques have been developed that measure the ammonia concentration of plasma.1" There are several theoretical advantages to the use of plasma which compensate for the additional step of separating plasma from blood. First, the ammonia concentration remains constant longer and increases more slowly in plasma than in whole blood.` Second, the increments in ammonia concentration of whole blood, which develop on standing, take place almost entirely within erythrocytes.t' Finally, the use of cation exchange resins, which cannot be applied satisfactorily to the measurement of ammonia in whole blood, permits quanti-tation of the preformed or "true" ammonia concentration in plasma,"8 rather than the "alkali-labile" ammonia measured by alkalinization methods which include ammonia derived from the alkaline hydrolysis of nitrogenous components of blood or plasma.'"89 Despite the use of plasma ammonia levels by some investigators and the development of numerous cation exchange methods for the measurement of ammonia in plasma, there are few data in the literature correlating whole blood and plasma ammonia concentrations. Seligson and Hirahara reported that the ammonia concentration of erythrocytes was two or three times as high as plasma and that the ammonia concentration of whole blood was almost twice as high as plasma.8 Humoller and his colleagues, in 21 normal subjects and 12 cirrhotic patients, found the ammonia concentration of * Associate Professor of Medicine. ** Supported in part by a grant from the Stratfield Fund. t Although ammonia exists almost completely as ammonium ion at the pH of normal blood, the term ammonia is used to refer to the total ammonia-ammonium level. t The increments in the ammonia concentration of whole blood which occur after anticoagulation with potassium oxalate or sodium fluoride:' has been shown in unpublished studies in this laboratory to occur almost completely in erythrocytes. Ammonia in blood, plasma, eiythrocytes I CONN erythrocytes to be less than one and one-half times as high as plasma ammonia levels over a wide range of ammonia values.' Jacquez and Parnas and their colleagues reported higher ammonia concentrations in whole blood than in plasma." Ternberg and Hershey, however, found the concentration of ammonia to be similar in whole blood and plasma of eight normal subjects.' The total number of patients with liver disease in which …