Metabolic Brain Disease

, Volume 20, Issue 3, pp 169–179 | Cite as

Ammonia and Hepatic Encephalopathy: The More Things Change, the More They Remain the Same

  • D. L. Shawcross
  • S. W. M. Olde Damink
  • R. F. Butterworth
  • R. JalanEmail author


Ammonia is thought to be central in the pathogenesis of hepatic encephalopathy and has been of importance to generations dating back to the early Egyptians. Hippocrates 2500 years ago described ‘encephalopathy’ simply translated as ‘inside head suffering.’ Over 1500 papers have been written on hepatic encephalopathy since 1966, but only a minority of these actually refer to the original observation of hepatic encephalopathy and the link with ammonia made by Marcel Nencki and Ivan Pavlov in 1893 with very little acknowledgement being made to the early landmark studies which described the importance of the muscle and kidneys in maintaining ammonia homeostasis as well as the liver and gut. Furthermore, infection was recognized as being an important modulator of brain function by the ancient Greek physicians and philosophers. This review focuses upon the original experiments of Nencki and Pavlov and describes how they fit into what we understand about the pathophysiology and treatment of hepatic encephalopathy today.


Ammonia hepatic encephalopathy nitrogen metabolism history of medicine 



hepatic encephalopathy


portacaval shunt


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • D. L. Shawcross
    • 1
  • S. W. M. Olde Damink
    • 2
  • R. F. Butterworth
    • 3
  • R. Jalan
    • 1
    • 4
    Email author
  1. 1.Liver Failure GroupInstitute of HepatologyLondonUnited Kingdom
  2. 2.Department of Surgery, Academic HospitalMaastricht UniversityThe Netherlands
  3. 3.Neuroscience Research UnitHôpital Saint-Luc (CHUM)MontréalCanada
  4. 4.Liver Failure GroupInstitute of HepatologyLondonUnited Kingdom

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