Hemolytic Crisis in a Dog with Copper-Associated Chronic Hepatitis
DOI:
https://doi.org/10.22456/1679-9216.97546Abstract
Background: Copper is an essential micronutrient for the body to function properly. However, although it is a vital element, an excess of copper in the body is extremely toxic. Copper toxicity has been reported mainly in sheep. In dogs, clinicopathological signs of toxicity are characterized by chronic liver failure. This means that the hemolytic crisis so common in sheep is a condition rarely associated with toxicity in dogs, so there are very few descriptions of this condition in the veterinary literature. The purpose of this report is to describe a case of hemolytic crisis in a dog with copper-associated chronic hepatitis.
Case: A medium-sized 6-year-old bitch was brought to the Veterinary Hospital of the Federal University of Santa Maria, with clinical presentation of apathy, anorexia and red urine. A physical examination revealed mildly jaundiced mucosa and dark brown urine. A urinalysis indicated the presence of protein, bilirubin and occult blood. The blood count revealed hypochromic macrocytic anemia, leukocytosis due to left shift neutrophilia and thrombocytopenia. Serum biochemistry showed elevated levels of alanine aminotransferase and alkaline phosphatase. The animal was given a blood transfusion due to the severity of her anemia, but her clinical condition worsened and she died, whereupon her body was sent for necropsy. This necropsy revealed conspicuous signs of jaundice, splenomegaly and altered liver and kidney color. The liver was brownish, with its natural surface firm and slightly irregular. The kidneys were diffusely blackened. The urine was dark brown. Fragments of different organs were collected, fixed in 10% buffered formalin solution, routinely processed for histopathology and stained with hematoxylin and eosin. A histological dissection of the liver showed the hepatic lobes dissected by fibrosis, forming islands of hepatocytes and numerous lymphocytes and plasmocytes. Brown granular pigment was observed in periportal hepatocytes. Perls Prussian blue and rubeanic acid staining techniques were performed to characterize this pigment. Most of the pigment reacted strongly to rubeanic acid and but not to Perls’ Prussian blue, thus characterizing it as copper. Random hepatic necrosis was visible. The kidneys contained hemoglobin and necrotic epithelial cells obstructing the renal tubules. Based on the clinical and anatomopathological aspects, a diagnosis of hemolytic crisis due to copper-associated chronic hepatitis was established.
Discussion: The most accepted mechanism to explain the occurrence of hemolysis is that copper long stored in hepatocytes is massively released into the bloodstream due to some stressful condition. When too much copper circulates in the bloodstream it inhibits enzymes that act on the energy metabolism of red blood cells, thereby lowering the synthesis of energy and nucleotides needed for glutathione activity, and causing hemoglobin to transform into methemoglobin. In the case reported here, copper toxicosis presumably originated from the animal’s diet since, according to the literature, the periportal distribution of copper revealed during histology suggests that the event resulted from excessive copper intake or was secondary to previous cholestatic liver injury. This paper describes a case of hemolytic crisis in a dog with copper-associated chronic hepatitis and, emphasizes the importance of including copper toxicity as a differential diagnosis for dogs presenting hemolytic crisis, in order to assist veterinarians in managing their patients.
Downloads
References
Asano R. & Hokari S. 1985. The effect of copper on intact cattle erythrocytes. Journal of Pharmacology and Therapeutics. 8: 157-164.
Bexfield N.H., Andres-Abdo C., Scase T.J., Constantino-Casas F. & Watson P.J. 2011. Chronic hepatitis in the english springer spaniel: clinical presentation, histological description and outcome. Veterinary Record. 169: 415.
Cedeño Y., López-Alonso M. & Miranda M. 2016. Hepatic concentrations of copper and other metals in dogs with and without chronic hepatitis. Journal of Small Animal Practice. 57: 703-709.
Cullen J.M. & Brown D.L. 2012. Hepatobiliary System and Exocrine pancreas. In: Zachary J.F. & Mc Gavin M.D. (Eds). Pathologic Basis of Veterinary Disease. 5th edn. St. Louis: Elsevier, pp.405-457.
Cullen J.M. & Stalker M.J. 2016. Liver and Biliary System. In: Maxie M.G. (Ed). Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th edn. St. Louis: Elsevier, pp.258-352.
Dirksen K., Spee B., Penning L.C., van den Ingh T.S.G.A.M., Burgener I.A., Watson A.L., Koerkamp M.G., Rothuizen J., Van Steenbeek F.G. & Fieten H. 2017. Gene expression patterns in the progression of canine copper-associated chronic hepatitis. Plos One. 12: 1-19.
Fighera R.A. & Graça D.L. 2016. Sistema Hematopoiético. In: Santos R.L. & Alessi A.C. (Eds). Patologia Veterinária. 2.ed. Rio de Janeiro: Roca, pp.311-406.
Fuentealba I., Haywood S. & Trafford J. 1989. Variations in the intralobular distribution of copper in the livers of copper-loaded rats in the relation to the pathogenesis of copper storage diseases. Journal of Comparative Pathology. 100: 1-11.
Hoffmann G., Van den Ingh., Bode P. & Rothuizen J. 2006. Copper-associated chronic hepatitis in Labrador Retrievers. Journal of Veterinary Internal Medicine. 20: 856-861.
Lang P.A., Schenck M., Nicolay J.P., Becker J.U., Kempe D.S., Lupescu A., Koka S., Eisele K., Klar B.A., , Rübben H., Schmid K.W., Mann K., Hildenbrand S., Hefter H., Huber S.M., Wieder T., Erhardt A., Häussinger D., Gulbins E. & Lang F. 2007. Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide. Nature Medicine. 13: 164-170.
Lemos R.A.A., Rangel J.M.R., Osório A.L.A.R., Moraes S.S., Nakazato L., Salvador S.C. & Martins S. 1997. Alterações clínicas, patológicos e laboratoriais na intoxicação crônica por cobre em ovinos. Ciência Rural. 27: 457-463.
Miguel M.P., Souza M.A., Cunha P.H.J., Costa G.L. & Abud L.J. 2013. Intoxicação crônica por cobre em ovinos: conduta para o diagnóstico conclusivo. Arquivo Brasileiro de Medicina Veterinária e Zootecnia. 65: 364-368.
Minervino A.H.H., Barrêto Júnior R.A., Ferreira R.N.F., Rodrigues F.A.M.L., Headley S.A., Mori C.S. & Ortolani E.L. 2009. Clinical observations of cattle and buffalos with experimentally induced chronic copper poisoning. Research in Veterinary Science. 87: 473-478.
Peters R. & Walshe J.M. 1966. Studies on the toxicity of copper. The toxic action of copper in vivo and in vitro. Proceedings of the Royal Society of London B. 166: 273-284.
Thornburg L.P. 2000. A perspective on copper and liver disease in the dog. Journal of Veterinary Diagnostic Investigation. 12: 101-110.
Walshe J.M. 2013. The acute haemolytic syndrome in Wilson’s disease – a review of 22 patients. Quarterly Journal of Medicine. 106: 1003-1008.
Watson A.D.J., Middleton D.J. & Ilkiw J.E. 1983. Copper storage disease with in travascular haemolysis in a Bedlington terrier. Australian Veterinary Journal. 60: 305-307.
Wijmenga C. & Klomp L.W.J. 2004. Molecular regulation of copper excretion in the liver. Proceedings of the Nutrition Society. 63: 31-39.
Xie J.J. & Wu Z.Y. 2017. Wilson’s Disease in China. Neuroscience Bulletin. 33: 323-330.
Published
How to Cite
Issue
Section
License
This journal provides open access to all of its content on the principle that making research freely available to the public supports a greater global exchange of knowledge. Such access is associated with increased readership and increased citation of an author's work. For more information on this approach, see the Public Knowledge Project and Directory of Open Access Journals.
We define open access journals as journals that use a funding model that does not charge readers or their institutions for access. From the BOAI definition of "open access" we take the right of users to "read, download, copy, distribute, print, search, or link to the full texts of these articles" as mandatory for a journal to be included in the directory.
La Red y Portal Iberoamericano de Revistas Científicas de Veterinaria de Libre Acceso reúne a las principales publicaciones científicas editadas en España, Portugal, Latino América y otros países del ámbito latino