Write a brief note on ammonia intoxication

·        It is the toxicity resulting from hyperammonemia

·        Normal plasma NH₃ concentration =10-80μg/dl.

·        This happen to occur due to

o   Hepatic dysfunction leading to impairment of urea cycle. eg. Cirrhosis of liver, hepatic failure

o   Deficiency of urea cycle enzyme. eg. Carbamoylphosphate synthase deficiency.

·        In this condition brain tissue is mostly affected and there is depression of cerebral activity. In neurons, excess ammonia converts α-ketoglutarate to glutamate and then to glutmine. This causes rapid depletion of α-ketoglutarate leading to suppression of TCA cycle since α-ketoglutarate is a functional component of TCA cycle. Suppression of TCA cycle culminates to ATP depletion which is assumed to be the cause of different signs and symptoms of ammonia intoxication like tremors, slurring of speech, blurring of vision, coma, death.