• 1. Goggs R, Serrano S, Szladovits B, et al. Clinical investigation of a point-of-care blood ammonia analyzer. Vet Clin Pathol 2008; 37: 198206.

    • Search Google Scholar
    • Export Citation
  • 2. Gerritzen-Bruning MJ, van den Ingh T, Rothuizen J. Diagnostic value of fasting plasma ammonia and bile acid concentrations in the identification of portosystemic shunting in dogs. J Vet Intern Med 2006; 20: 1319.

    • Search Google Scholar
    • Export Citation
  • 3. Strombeck DR, Meyer DJ, Freedland RA. Hyperammonemia due to a urea cycle enzyme deficiency in two dogs. J Am Vet Med Assoc 1975; 166: 11091111.

    • Search Google Scholar
    • Export Citation
  • 4. Zandvliet MM, Rothuizen J. Transient hyperammonemia due to urea cycle enzyme deficiency in Irish Wolfhounds. J Vet Intern Med 2007; 21: 215218.

    • Search Google Scholar
    • Export Citation
  • 5. Center SA, Magne ML. Historical, physical examination, and clinicopathologic features of portosystemic vascular anomalies in the dog and cat. Semin Vet Med Surg (Small Anim) 1990; 5: 8393.

    • Search Google Scholar
    • Export Citation
  • 6. Albrecht J, Dolinska M. Glutamine as a pathogenic factor in hepatic encephalopathy. J Neurosci Res 2001; 65: 15.

  • 7. Prakash R, Mullen KD. Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 2010; 7: 515525.

    • Search Google Scholar
    • Export Citation
  • 8. Lemberg A, Fernández MA. Hepatic encephalopathy, ammonia, glutamate, glutamine and oxidative stress. Ann Hepatol 2009; 8: 95102.

  • 9. Norenberg MD, Martinez-Hernandez A. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res 1979; 161: 303310.

    • Search Google Scholar
    • Export Citation
  • 10. Norenberg MD. The role of astrocytes in hepatic encephalopathy. Neurochem Pathol 1987; 6: 1333.

  • 11. Lockwood AH. Blood ammonia levels and hepatic encephalopathy. Metab Brain Dis 2004; 19: 345349.

  • 12. Lockwood AH, Yap EW, Wong WH. Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy. J Cereb Blood Flow Metab 1991; 11: 337341.

    • Search Google Scholar
    • Export Citation
  • 13. Broome CJ, Walsh VP, Braddock JA. Congenital portosystemic shunts in dogs and cats. N Z Vet J 2004; 52: 154162.

  • 14. Butterworth J, Gregory CR, Aronson LR. Selective alterations of cerebrospinal fluid amino acids in dogs with congenital portosystemic shunts. Metab Brain Dis 1997; 12: 299306.

    • Search Google Scholar
    • Export Citation
  • 15. Holt DE, Washabau RJ, Djali S, et al. Cerebrospinal fluid glutamine, tryptophan, and tryptophan metabolite concentrations in dogs with portosystemic shunts. Am J Vet Res 2002; 63: 11671171.

    • Search Google Scholar
    • Export Citation
  • 16. Meyer HP, Legemate DA, van den Brom W, et al. Improvement of chronic hepatic encephalopathy in dogs by the benzodiazepine-receptor partial inverse agonist sarmazenil, but not by the antagonist flumazenil. Metab Brain Dis 1998; 13: 241251.

    • Search Google Scholar
    • Export Citation
  • 17. Bhatia V, Singh R, Acharya SK. Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut 2006; 55: 98104.

    • Search Google Scholar
    • Export Citation
  • 18. Bernal W, Hall C, Karvellas CJ, et al. Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology 2007; 46: 18441852.

    • Search Google Scholar
    • Export Citation
  • 19. Rothuizen J, van den Ingh TS. Arterial and venous ammonia concentrations in the diagnosis of canine hepato-encephalopathy. Res Vet Sci 1982; 33: 1721.

    • Search Google Scholar
    • Export Citation
  • 20. Torisu S, Washizu M, Hasegawa D, et al. Brain magnetic resonance imaging characteristics in dogs and cats with congenital portosystemic shunts. Vet Radiol Ultrasound 2005; 46: 447451.

    • Search Google Scholar
    • Export Citation
  • 21. Morandi F, Cole RC, Tobias KM, et al. Use of 99mTCO4(−) trans-splenic portal scintigraphy for diagnosis of portosystemic shunts in 28 dogs. Vet Radiol Ultrasound 2005; 46: 153161.

    • Search Google Scholar
    • Export Citation
  • 22. Carrera I, Kircher PR, Meier D, et al. In vivo proton magnetic resonance spectroscopy for the evaluation of hepatic encephalopathy in dogs. Am J Vet Res 2014; 75: 818827.

    • Search Google Scholar
    • Export Citation
  • 23. Lockwood AH, McDonald JM, Reiman RE, et al. The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J Clin Invest 1979; 63: 449460.

    • Search Google Scholar
    • Export Citation
  • 24. Brusilow SW, Koehler RC, Traystman RJ, et al. Astrocyte glutamine synthetase: importance in hyperammonemic syndromes and potential target for therapy. Neurotherapeutics 2010; 7: 452470.

    • Search Google Scholar
    • Export Citation
  • 25. Felipo V, Butterworth RF. Neurobiology of ammonia. Prog Neurobiol 2002; 67: 259279.

  • 26. Braissant O, McLin VA, Cudalbu C. Ammonia toxicity to the brain. J Inherit Metab Dis 2013; 36: 595612.

  • 27. Cagnon L, Braissant O. Hyperammonemia-induced toxicity for the developing central nervous system. Brain Res Rev 2007; 56: 183197.

  • 28. Cudalbu C. In vivo studies of brain metabolism in animal models of hepatic encephalopathy using 1H magnetic resonance spectroscopy. Metab Brain Dis 2013; 28: 167174.

    • Search Google Scholar
    • Export Citation
  • 29. Albrecht J, Zielinska M, Norenberg MD. Glutamine as a mediator of ammonia neurotoxicity: a critical appraisal. Biochem Pharmacol 2010; 80: 13031308.

    • Search Google Scholar
    • Export Citation
  • 30. Brusilow SW, Traystman R. Hepatic encephalopathy. N Engl J Med 1986; 314: 786787.

  • 31. Ong JP, Aggarwal A, Krieger D, et al. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med 2003; 114: 188193.

    • Search Google Scholar
    • Export Citation
  • 32. Or M, Peremans K, Martlé V, et al. Regional cerebral blood flow assessed by single photon emission computed tomography (SPECT) in dogs with congenital portosystemic shunt and hepatic encephalopathy. Vet J 2017; 220: 4042.

    • Search Google Scholar
    • Export Citation
  • 33. Ott P, Larsen FS. Blood-brain barrier permeability to ammonia in liver failure: a critical reappraisal. Neurochem Int 2004; 44: 185198.

    • Search Google Scholar
    • Export Citation
  • 34. Ruland K, Fischer A, Hartmann K. Sensitivity and specificity of fasting ammonia and serum bile acids in the diagnosis of portosystemic shunts in dogs and cats. Vet Clin Pathol 2010; 39: 5764.

    • Search Google Scholar
    • Export Citation

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Ammonia concentrations in arterial blood, venous blood, and cerebrospinal fluid of dogs with and without congenital extrahepatic portosystemic shunts

Matan Or DVM, Phd1, Nausikaa Devriendt DVM2, Adriaan M. Kitshoff DVM3, Kathelijne Peremans DVM, Phd4, Eva Vandermeulen DVM, Phd5, Dominique Paepe DVM, Phd6, Ingeborgh Polis DVM, Phd7, Valentine Martlé DVM, Phd8, and Hilde de Rooster DVM, Phd9
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  • 1 Department of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke 9820, Belgium.
  • | 2 Department of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke 9820, Belgium.
  • | 3 Department of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke 9820, Belgium.
  • | 4 Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke 9820, Belgium.
  • | 5 Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke 9820, Belgium.
  • | 6 Department of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke 9820, Belgium.
  • | 7 Department of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke 9820, Belgium.
  • | 8 Department of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke 9820, Belgium.
  • | 9 Department of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke 9820, Belgium.

Abstract

OBJECTIVE To compare ammonia concentrations in arterial blood, venous blood, and CSF samples of dogs with and without extrahepatic portosystemic shunts (EHPSS).

ANIMALS 19 dogs with congenital EHPSS and 6 healthy control dogs.

PROCEDURES All dogs underwent a physical examination and then were anesthetized for transsplenic portal scintigraphy to confirm the presence or absence of EHPSS. While dogs were anesthetized, arterial and venous blood samples and a CSF sample were simultaneously collected for determination of ammonia concentration, which was measured by use of a portable blood ammonia analyzer (device A) and a nonportable biochemical analyzer (device B). Results were compared between dogs with EHPSS and control dogs.

RESULTS Arterial, venous, and CSF ammonia concentrations for dogs with EHPSS were significantly greater than those for control dogs. For dogs with EHPSS, ammonia concentrations in both arterial and venous blood samples were markedly increased from the reference range. There was a strong positive correlation between arterial and venous ammonia concentrations and between blood (arterial or venous) and CSF ammonia concentrations.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that blood and CSF ammonia concentrations in dogs with EHPSS were greater than those for healthy dogs and were strongly and positively correlated, albeit in a nonlinear manner. This suggested that the permeability of the blood-brain barrier to ammonia may be abnormally increased in dogs with EHPSS, but further investigation of the relationship between blood or CSF ammonia concentration and clinical signs of hepatic encephalopathy or the surgical outcome for dogs with EHPSS is warranted.

Contributor Notes

Dr. Or's present address is Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Address correspondence to Hilde de Rooster (hilde.derooster@ugent.be).