Studies on the Origin and Significance of Blood Ammonia

Resurgence of interest in ammonia metabolism in liver disease has resulted in extensive use of the blood ammonia determination as a clinical and investigative tool. Almost all methods for the determination of ammonia in blood are based on the liberation of ammonia by alkalinization, diffusion of the ammonia into an acid medium, followed by titrimetric or colorimetric quantitation. Although widely used, these measurements have been accepted with reservations for several reasons. First, a wide variation in the normal range of blood ammonia concentration has been reported from various laboratories."5 These may be attributed to technical differences in degree of alkalinization, "'8 duration of diffusion,8'e'9 interval between the shedding of blood and its analysis,""' temperature1' l" and other factors. Secondly, there has been controversy over whether free ammonia actually exists in the circulating blood of normal individuals. Conway observed a sharp rise in the blood ammonia concentration immediately after shedding and concluded that the circulating blood of normal individuals does not contain free ammonia.' Some investigators have confirmed this observatione9'1 but others, using the same or different methods, have been unable to do so.' 7''l Although it appears that free ammonia does exist in blood in low concentrations,19'f one must assume that the blood ammonia levels, as measured by some, if not all, of these different techniques, are artifactually high or low. The recent observation that different commercial brands and concentrations of heparin contain variable amounts of ammonia which may artifactually affect the blood ammonia level,' has led to investigations of the effect of other anticoagulants. Use of anticoagulants such as heparin, potassium oxalate and sodium fluoride, which are themselves ammonia-free, may affect the blood ammonia determination to different degrees.-' These