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Ammonia toxicity: from head to toe?

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Abstract

Ammonia is diffused and transported across all plasma membranes. This entails that hyperammonemia leads to an increase in ammonia in all organs and tissues. It is known that the toxic ramifications of ammonia primarily touch the brain and cause neurological impairment. However, the deleterious effects of ammonia are not specific to the brain, as the direct effect of increased ammonia (change in pH, membrane potential, metabolism) can occur in any type of cell. Therefore, in the setting of chronic liver disease where multi-organ dysfunction is common, the role of ammonia, only as neurotoxin, is challenged. This review provides insights and evidence that increased ammonia can disturb many organ and cell types and hence lead to dysfunction.

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Authors and Affiliations

  1. Department of Gastroenterology, Hepatology and Pathobiology, Cleveland Clinic, Cleveland, OH, USA

    Srinivasan Dasarathy

  2. Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK

    Rajeshwar P. Mookerjee

  3. Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

    Veronika Rackayova

  4. Department of Ophthalmology, Haukeland University Hospital, 5021, Bergen, Norway

    Vinita Rangroo Thrane

  5. Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, USA

    Vinita Rangroo Thrane

  6. Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Dhanvantri Nagar, Pondicherry, India

    Balasubramaniyan Vairappan

  7. Department of Medicine V (Hepatology and Gastroenterology), Aarhus, Denmark

    Peter Ott

  8. Hepato-Neuro Laboratory, CRCHUM, Department of Medicine, Université de Montréal, Montréal, Québec, Canada

    Christopher F. Rose

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  1. Srinivasan Dasarathy
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  2. Rajeshwar P. Mookerjee
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  3. Veronika Rackayova
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  4. Vinita Rangroo Thrane
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  5. Balasubramaniyan Vairappan
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  6. Peter Ott
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  7. Christopher F. Rose
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Correspondence to Christopher F. Rose.

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The authors have no conflicts to disclose. SD supported in part by NIH grants: RO1 DK 83414, R21 AA 022742, UO1 AA021893 and P50 AA024333 8236.

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Dasarathy, S., Mookerjee, R.P., Rackayova, V. et al. Ammonia toxicity: from head to toe?. Metab Brain Dis 32, 529–538 (2017). https://doi.org/10.1007/s11011-016-9938-3

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