Ammonia pathophysiology

Infection, gastrointestinal bleeding or injudicious use of sedatives and diuretics can precipitate hepatic encephalopathy in cirrhotic patients. The pathophysiology is complex but ammonia appears to hold a central role. Derived mainly from the action of colonic urease-containing bacteria, ammonia is... 

The pathophysiology of hepatic encephalopathy is not completely understood but includes an increased sensitivity to dietary proteins. Ammonia concentrations are always increased with acute encephalopathy and usually increased with chronic encephalopathy. A reduction of plasma ammonia is often associated with symptomatic improvement. However, since plasma ammonia concentrations do not correlate with the severity of the encephalopathy, it has been suggested that other factors are involved. It is now recognized that a variety of neurotransmitter systems are dysfunctional in hepatic encephalopathy, but the exact cause for the changes is not known. One important contributor is the endogenous benzodiazepine agonist system, but other abnormalities must be invoked to explain all the findings. ... 

Nath KA, Hostetler MK, Hostetler TH. Pathophysiology of chronic tubulo-interstitial disease in rats. Interactions of dietary acid load, ammonia, and complement component C3. J CUn Invest 1985 76 667-675. 

Ammonia also has deleterious effects on excitatory neurotransmission (Szerb and Butterworth, 1992, review) where effects on both presynaptic and postsynaptic neuronal membranes have been reported. NH + ions, in pathophysiologically relevant concentrations, interfere with excitatory neurotransmission by preventing the action of glutamate at the postsynaptic receptor. In addition, NH depolarizes neurons to a variable degree without consistently changing membrane resistance, probably by reducing K concentrations. 

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