AMMONIUM SALT APPLICATION ON HEPATIC ENCEPHALOPATHY (HE) SUBJECTS Aníbal Tornés Blanco
Aug 13, 2015
Thesis Statement
Application of Ammonium Salts has shown to arouse brain tissue in Hepatic Encephalopathy (HE) through a 2nd absorption pathway as therapy for brain function re-establishment along:
Rifaximin and Lactulose treatment.
Hepatic Encephalopathy (HE)
Neurodegenerative diminishment of Brain Functions.
Toxic-Metabolic Encephalopathy. “When the free radicals of these toxics reach soft tissues such as the
brain, the Central Nervous System (CNS) may decay to a comatose state” (Fereneci et al. 1998)
Liver Malfunction Hepatitis – Inflammation of liver cells. Cirrhosis – Loss of liver cells and scarring.
Alcohol , Hepatitis B and C
Ammonia Concentration Hypothesis
“Ammonia depends upon the place from where it is withdrawn, and peripheral veins may not express the amount of ammonia concentration in all the blood in the body” (Bessman, et al. 1954-1955) and (Webster et al.1955)
HE Pathogenesis effect in brain matter
Grey Matter – More axons and Neuron Synapses with High Myelin consistency.
White Matter – Lack of Myelin consistency and works as Axon connectors.
Ammonia to blame?
Grey Matter Density Loss
Subpanel A
Cirrhotic without HE
Subpanel B
Cirrhotic with minimal HE
Subpanel C
Cirrhotic & recurring HE
White Matter Density Loss
Subpanel D
Cirrhotic without HE
Subpanel E
Cirrhotic & minimal HE
Subpanel F
Cirrhotic & recurring HE
Journal of Hepatology, 2011 vol.55 I 564-573
Compared to Healthy Population (51)
(Guevara et al. 2011)
VBM Contrast Conclusions
“Neurotoxins produced during HE from the liver are the complication factors behind the brain tissue density deterioration” (Guevara et al. 2010)
Rifaximin & Lactulose Treatment
Rifaximin Stands out from other antibiotics, Limits harmful bacteria
gut from forming due to negligible plasma level compliance.
Lactulose, Disaccharide that aims to
reduce blood pH, drawing ammonia out of the body.
Conclusion
“Ammonium Salts have the capacity to cross the blood brain barrier and influence directly the blood pH” (Warren, 1957)
References
1. Ferenci P, Lockwood A, Mullen K, Tater R, Weissenborn K, Blei A, et al. Hepatic encephalopathy – definition, nomenclature, diagnosis and quantification: final report of the Working Party at the 11th World Congress of Gastroenterology, Vienna, 1998. Hepatology 2002;35:716–721.
2. ADAMS, R. D, and FOLEY, J. M. (I953), 'Metabolic and Toxic Diseases of the Nervous System,' Vol. XXXII, The Williams & Wilkins Co., Baltimore, U.S.A
3. WEBSTER, L. T. Jr., and DAVIDSON, C. S. (1956), J. din. Invest., 35, I9I. 4. Hahn, M, Massen, O., Nencki, M. et al. Diebeck'sche fistel zwischen der untern
hohlvene und der pfortader und ihre folgen fur den organismus. Arch Exp Pathol Pharmacol. 1893; 32: 161–210
5. Shawcross DI, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, Taylor NJ, Auzinger G,Bernal W, Wendon JA. 2011. Infection and Systemic Inflammation, not Ammonia, are Associated with Grade 3/4 Hepatic Encephalopathy, but not Mortality in Cirrhosis. Journal of Hepatology 54(4):640 649. doi:10.1016/j.jhep.2010.07.045
References
6. Guevara M, Baccaro M, Gómez , Anson B, Frisoni G, Testa C, Torre A, Molinuevo J, Rami L,Pereira G, Urtasun Sotil E et al. Cerebral magnetic resonance imaging reveals marked abnormalities of brain tissue density in patients with cirrhosis without overt hepatic encephalopathy. Journal of Hepatology 55(3):564 573. doi.org:10.1016/j.jhep.2010.12.008
7. Bass N, Mullen K, Sanyal A, Poordad F, Neff G, Leevy C, Sigal S, Sheikh M, Beavers K,Frederick T et al. 2010. Rifaximin Treatment in Hepatic Encephalopathy. The New England Journal of Medicine 362(12):1071 1081. doi.org:10.1056/NEJM
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Glasgow Coma Scale (GCS)
Assesment for conscious state.
Lowest Possible is 3 – Deep Coma or Death Highest Possible is 15 – Fully awake
1 2 3 4 5 6
Eye response No Response Response to pain Response to voice Responds Spontaneously
N/A N/A
Verbal Response
No Response Incomprehensive Sounds
Unintelligent Words Confused, disoriented Normal conversation
N/A
Motor Response
No Response Response to pain Decerebrate Response
Response to pain Decortícate Response
Withdraws to stimulu and Flexion
Localizes painful stimuli
Obeys Commands