Copper Toxicity in Rabbits

• Copper (Cu). (J212.8.w2, J495.42.w4)
  • It was thought that copper sulphate in feed was not properly mixed with other feed ingredients during compounding. Selected feed pellets which were bluish-green in colour contained 447 ppm copper, compared with 22 ppm for a general feed sample. It was possible that individual rabbits were attracted to the copper-rich pellets, or that some batch(s) contained an excess amount of copper. (J212.8.w2)

Clinical signs

• Found dead. (J212.8.w2)
• Weakness and depression, or found dead. (J495.42.w4)
• Blood smears: with Giemsa staining, red blood cells seen to be crenellated and fragmenting, with anisocytosis and rouleaux formations. (J212.8.w2)
  • Indicative of intravascular haemolysis. (J212.8.w2)

Pathological findings

Gross pathology

• General:
  • Pallor of oral mucosa and of internal tissues. (J495.42.w4)
  • In one animal, fresh blood in the abdominal cavity (haemorrhage from ruptured liver). (J212.8.w2)
• Urinary bladder:
  • Contained red-tinged urine. (J495.42.w4)
  • Urine port-wine colour. (J212.8.w2)
• Liver: enlarged, friable, yellow-green colour. (J212.8.w2)
• Spleen: enlarged. (J212.8.w2)
• Renal: kidneys swollen, dark. (J212.8.w2)

Histopathology

• Hepatic:
  • "Kupffer cells had abundant cytoplasm filled with granular, gray-green pigment." Macrophages filled with similar pigment were found in small agreggates. Portal areas tended to contain mononuclean phagocytic cells more commonly than other areas; lymphocytes, plasma cells and neutrophils were also found near these cells. Occasional hepatocytes contained the pigment. Centrilobular vacuolar degeneration of hepatocytes, mild to moderate, was noted. (J495.42.w4)
    • The pigment was shown by the rhodanine technique to be copper. (J495.42.w4)
    • Analysis of liver tissue, following storage in 10% buffered formalin for 16 days, was 4,012 ppm copper, on a wet weight basis. This compares to 30.1, 36.8 and 70.8 ppm for liver from three normal New Zealand white rabbits (reduced to 19.8, 22.5 and 52.0 ppm after storage in formalin for 16 days). The copper content of the fresh liver would probably have been over 6,000 ppm. (J495.42.w4)
  • Mild centrilobular fatty change, hyperplasia of bile ducts and hepatic necrosis. Around portal triads, Kuppfer cells, multinucleate giant cells and hepatocytes containing brownish pigmented granules. (J212.8.w2)
    • The pigment was shown by the rhodanine technique to be copper. (J212.8.w2)
    • Livers contained 532 - 1,250 ppm copper. (J212.8.w2)
• Spleen:
  • Erythrophagocytosis and haemosiderosis. (J212.8.w2)
• Renal:
  • In the cortex, "multifocal ectasia of proximal and distal tubules with flattening of epithelial cells." In the lumina, fine to coarse granular material which was brightly eosinophilic and consistent with haemoglobin. Degeneration of proximal, and less commonly distal, tubules was noted, with focal necrosis. Intracytopasmic haemoglobin-like pigment was present in many cells. (J495.42.w4)
  • Nephrosis; hyaline and granular tubular casts. (J212.8.w2)
    • Kidney contained 12.8 and 16.9 ppm copper. (J212.8.w2)

• Copper toxicity was reported in a single two-year-old New Zealand white rabbit which was found dead by a rabbit grower. (J495.42.w4) 
• Copper toxicity was reported in New Zealand white breeder rabbits. Most affected individuals were lactating or pregnant females, which might have been susceptible to toxicity due to the physiological stresses of lactation and gestation. (J212.8.w2)
• Normal liver copper concentration (wet weight) 8 - 50 ppm. (J212.8.w2)

Diagnosis

• Copper toxicity was diagnosed on the basis of the tissue pallor, red-tinged urine, histopathological findings (excess copper in hepatocytes, haemoglobinuric nephrosis) and the copper level in the liver. (J495.42.w4)
• Note: No reason could be found why this single individual developed copper toxicity. (J495.42.w4)

• Environmental Assessment
• History & Documentation
• Physical Examination of Mammals
• Necropsy of Mammals
• Imaging in Lagomorph Diagnosis and Treatment
• Clinical Pathology of Lagomorphs
• Treatment and Care
• Environmental and Population Management
• Preventative Medicine for Mammals
• Chapter 2 - B36 Field Manual of Wildlife Diseases - Specimen Collection and Preservation
• Chapter 3 - B36 Field Manual of Wildlife Diseases - Specimen shipment
• Appendix A - B36 Field Manual of Wildlife Diseases - Sample specimen history form

• Oryctolagus cuniculus domesticus - Domestic European rabbit