Fig. 2.

Inter-organ trafficking of ammonia under normal physiological conditions. Ammonia produced principally from protein digestion in the gastrointestinal tract or in part from glutamine via glutaminase in the kidney is removed in the liver as urea by periportal hepatocytes or as glutamine by perivenous hepatocytes. Ammonia is transported to the brain and to skeletal muscle where the sole mechanism for ammonia removal is via glutamine synthesis. In severe liver disease, hepatic ammonia removal capacity is decreased and skeletal muscle takes over as the major ammonia-removing organ. This pathway may be compromised by muscle wasting (sarcopenia) in cirrhosis