The Passage of Ammonia Across the Blood-Brain-Barrier and its Relation to Blood pH

Abstract

LD50 doses of 5 ammonium salts of varying pH were injected intravenously into mice. The blood and brain concentrations were measured at certain time intervals following injection. The more alkaline salts contained lower LD50 doses of ammonia N and the lethal blood levals associated with their administration were considerably lower than the blood levels produced by LD50 doses of acid salts. The cerebral ammonia N concentrations were, however, essentially similar for each salt. It is concluded that the pH of the blood regulates the partition of total ammonia between NH3 and NH4. Since the pKbh of ammonium is very nearly 8.9 at 37[degree] C. tne more alkaline salts will tend to increase the concentration of NH3. The latter penetrates the blood brain barrier far more readily than NH4. The toxicity of a given blood level of ammonia may be predicted more accurately if both the arterial concentration and the arterial pH are known.