Refining the Ammonia Hypothesis Elliot B. Tapper, MD, Z. Gordon Jiang, MD, PhD, Vilas R. Patwardhan, MD  Mayo Clinic Proceedings  Volume 90, Issue 5, Pages 646-658 (May 2015) DOI: 10.1016/j.mayocp.2015.03.003 Copyright © 2015 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 1 The neuropathology of hepatic encephalopathy reflects the interplay of ammonia, glutamine, and inflammation. GABA-A = γ-aminobutyric acid type A; NMDA = N-methyl-d-aspartate receptor. Mayo Clinic Proceedings 2015 90, 646-658DOI: (10.1016/j.mayocp.2015.03.003) Copyright © 2015 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 2 Sources of hyperammonemia and ammonia toxicity: multiorgan mechanisms. Mayo Clinic Proceedings 2015 90, 646-658DOI: (10.1016/j.mayocp.2015.03.003) Copyright © 2015 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 3 Target-based treatment of hepatic encephalopathy suggested by a refined ammonia hypothesis. TIPS = transjugular intrahepatic portosystemic shunt. Mayo Clinic Proceedings 2015 90, 646-658DOI: (10.1016/j.mayocp.2015.03.003) Copyright © 2015 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 4 A physiology-driven protocol for the treatment of hepatic encephalopathy. BID = twice daily; q2 - q4 = every 2-4 hours; TID = 3 times daily; TIPS = transjugular intrahepatic portosystemic shunt. Mayo Clinic Proceedings 2015 90, 646-658DOI: (10.1016/j.mayocp.2015.03.003) Copyright © 2015 Mayo Foundation for Medical Education and Research Terms and Conditions