ReviewRefining the Ammonia Hypothesis: A Physiology-Driven Approach to the Treatment of Hepatic Encephalopathy
Section snippets
Methods
A search of the representative literature was performed. Articles were collected through a search of MEDLINE/PubMed, Cochrane Database of Systematic Reviews, and Google Scholar and by a manual search of citations within retrieved articles. Search dates spanned October 1, 1948, to December 8, 2014. Search terms included hepatic encephalopathy [MeSH], ammonia hypothesis, brain and ammonia, liver failure and ammonia, acute-on-chronic liver failure and ammonia, cirrhosis and ammonia, portosytemic
Putting it All Together
By focusing on the determinants of ammonia metabolism and neurotoxicity, clinicians may develop an effective multimodal therapeutic strategy for their patients with HE. In patients with cirrhosis and portosystemic shunting, amino acid bypass of the liver in the postabsorptive state and loss of intrinsic hepatic function significantly raise the importance of alternative sites of ammonia metabolism. Namely, the muscle and kidney are critical for maintaining ammonia homeostasis (Figures 1 and 2).
Conclusion
In summary, the ideal therapeutic approach to patients with HE can be guided by a refined ammonia hypothesis. This refined and up-to-date view of the ammonia hypothesis is one that acknowledges the contribution of inflammation to the neurotoxicity of serum ammonia and underscores the importance of multiple organ systems, namely, the gut, kidney, and skeletal muscle, in achieving ammonia homeostasis.
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