AMMONIUM SALT APPLICATION ON HEPATIC ENCEPHALOPATHY (HE) SUBJECTS

Aníbal Tornés Blanco

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

Ammonium Carbonate (NH4)2CO3

Ammonium Salt family.

Ammonia NH3

Produced by protein decomposition.

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“Ammonia depends upon the place from where it is withdrawn, and peripheral veins may not express the amount of ammonia concentration in all the blood in the body” (Bessman, et al. 1954-1955) and (Webster et al.1955)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)

Ammonium Carbonate on Sharks

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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Questions

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