Metabolic Brain Disease

, Volume 32, Issue 2, pp 529–538 | Cite as

Ammonia toxicity: from head to toe?

  • Srinivasan Dasarathy
  • Rajeshwar P. Mookerjee
  • Veronika Rackayova
  • Vinita Rangroo Thrane
  • Balasubramaniyan Vairappan
  • Peter Ott
  • Christopher F. RoseEmail author
Original Article


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.


Ammonia Brain Muscle Hepatic encephalopathy Toxicity Liver 


Compliance with ethical standards


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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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Srinivasan Dasarathy
    • 1
  • Rajeshwar P. Mookerjee
    • 2
  • Veronika Rackayova
    • 3
  • Vinita Rangroo Thrane
    • 4
    • 5
  • Balasubramaniyan Vairappan
    • 6
  • Peter Ott
    • 7
  • Christopher F. Rose
    • 8
    Email author
  1. 1.Department of Gastroenterology, Hepatology and PathobiologyCleveland ClinicClevelandUSA
  2. 2.Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free HospitalLondonUK
  3. 3.Laboratory of Functional and Metabolic ImagingEcole Polytechnique Fédérale de Lausanne (EPFL)LausanneSwitzerland
  4. 4.Department of OphthalmologyHaukeland University HospitalBergenNorway
  5. 5.Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of NeurosurgeryUniversity of Rochester Medical CenterRochesterUSA
  6. 6.Department of BiochemistryJawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)PondicherryIndia
  7. 7.Department of Medicine V (Hepatology and Gastroenterology)AarhusDenmark
  8. 8.Hepato-Neuro Laboratory, CRCHUM, Department of MedicineUniversité de MontréalMontréalCanada

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