As clinical and experimental knowledge of ammonia metabolism increases, the relationship between increased concentrations of ammonia in the blood and the clinical state of "hepatic coma" becomes apparent. The occurrence of significantly increased concentrations of ammonia in the blood of patients with "hepatic coma" and the clearing of the sensorium that follows a reduction of the blood ammonia concentration both indicate that ammonia intoxication is an important factor in the production of hepatic encephalopathies. Further confirmation of an etiologic role of ammonia in "hepatic coma" is to be found in the fact that this syndrome can be reproduced in both experimental animals and human subjects by increasing the blood ammonia, either by the administration of ammonium salts or by the feeding of high-protein diets or urea. In patients who have had vascular shunting procedures done for portal hypertension, or in patients in whom chronic liver disease is associated with gastrointestinal
NAJARIAN JS, HARPER HA, McCORKLE HJ. Recognition and Treatment of Alterations in Ammonia Metabolism. AMA Arch Surg. 1959;79(4):621–629. doi:10.1001/archsurg.1959.04320100087016
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