Hepatic copper concentration was elevated. Copper toxicity in the camelid is difficult to diagnose, since the classical ..... Puls R. Mineral Levels in Animal Health.
Suspect copper toxicity in an alpaca James L. Carmalt, Keith E. Baptiste, Barry Blakley An alpaca presented in lateral recumbency and subsequently died. On necropsy Abstract examination the liver showed severe, widespread, periacinar hepatocellular necrosis, staining positive to a rhodamine stain for copper. Hepatic copper concentration was elevated. Copper toxicity in the camelid is difficult to diagnose, since the classical hemolytic crisis is not observed.
Resume Suspicion d'intoxication au cuivre chez un alpaca. Un alpaca present6 en etat de d6cubitus lateral est mort par la suite. A la n6cropsie, le foie presentait une necrose hepatocellulaire periacineuse etendue et severe, se colorant positivement par une rhodamine servant a detecter le cuivre. La concentration en cuivre du foie etait elevee. La toxicite du cuivre chez les camelides est difficile a diagnostiquer puisque la crise hemolytique classique n'est pas observee. (Traduit par Docteur Andre Blouin) Can Vet J 2001;42:554-556
A 10-year-old, 65-kg, female alpaca was presented for acute anorexia and recumbency. Vaccinations against Clostridium perfringens types C and D and C. tetani were current. The alpaca and the rest of the 15-animal herd had been dewormed every other month with ivermectin. The herd had been fed a commercial pelleted ration for 4 y. The alpaca had not eaten this ration the previous day, but it had continued to graze, eat its alfalfa hay ration, and drink normally. It continued to pass urine and feces normally. Early the next morning, the alpaca was reluctant to come to the feeders and, soon, was in lateral recumbency and unresponsive. A veterinarian attended, gave 5 mL of procaine
penicillin (Ethacillin; rogar/STB, London, Ontario), IM, and referred the animal to the Western College of Veterinary Medicine (WCVM) for further evaluation. No other animals in the herd showed behavioral or clinical signs of disease. On presentation, the alpaca was in lateral recumbency, unresponsive, and severely dyspneic (17 breaths/ min); its temperature was within normal limits (37.9°C; reference range, 37.5°C to 38.8°C). Thoracic auscultation at this time revealed slightly increased lung sounds bilaterally. The alpaca was bradycardic (56 beats/min; reference range, 60 to 80 beats/min), but the rhythm was normal. Mucous membranes were dark purple and gut motility was reduced. Thoracic ultrasound was performed due to the increased lung sounds and was unremarkable (no areas of consolidation, increased pleural fluid, or adhesions). Peritoneal fluid, obtained by abdominocentesis, was also normal. Blood was submitted for a complete blood cell count, and serum biochemical and venous blood gas analysis. Results showed neutrophilia (25.9 X Department of Large Animal Clinical Sciences (Carmalt, Baptiste), Department of Veterinary Biomedical Sciences (Blakley), Westem College of Veterinary Medicine, 52 Campus
Drive, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B4. Address correspondence to Dr. Carmalt. Reprints will not be available from the authors. 554
109 cells/L; reference range, 2.0 to 13.3 X 109/L) (1), lymphopenia (0.58 X 109 cellsAL; reference range, 2.1 to 6.8 X 109/L), and hyperfibrinogenemia (7 g/L; reference range, 1 to 5 g/L) (2). Also present were a hyperglycemia (16.2 mmol/L; reference range, 4.3 to 8.5 mmol/L) and a mild increase in gammaglutamyltransferase (GGT) (29 U/L; reference range, 3 to 28 U/L). Sorbitol dehydrogenase (SDH) and aspartate transaminase (AST) values, 5.7 U/L and 332 U/L, respectively, were within reference ranges (0 to 15 U/L and 128 to 450 U/L, respectively). The only abnormality present on venous blood gas analysis was a low PvO2 (32.9 mmHg). An IV catheter was placed in the right jugular vein and lactated Ringer's solution administered at a rate of 6 mL/min. Flunixin meglumine (Banamine; ScheringPlough, Pointe Claire, Quebec), 50 mg, IV, and oxytetracycline (Liquamycin LP; rogar/STB), 500 mg, IV, were administered in the interim period, as an infectious or traumatic disorder of the central nervous system (CNS) was tentatively suspected. Oxygen was administered via an indwelling nasal catheter at a flow rate of 15 L/min; this raised the venous pO2 to 349.2 mmHg with no significant improvement in respiratory effort or in the color of the mucous membranes. The following morning, the alpaca was hypothermic (36.5°C), dyspneic, and breath holding, and displayed an expiratory grunt and openmouthed breathing. The neck was in an opisthotonic position. Occasional movements of the head and legs could be elicited in response to stimuli. A lumbosacral cerebrospinal tap was performed and 1.5 mL of clear colorless fluid was recovered. The nucleated cell count was normal (0.001 x 109 cells/L; reference range 0.001 to 0.015 X 109/L), but protein and the erythrocyte count were elevated (1.54 g/L; reference range 0.2 to 0.5 g/L and 3 X 106/L; reference range, 0 x 106/L, respectively) (3). The elevated erythrocyte levels were most likely due to contamination during collection. Later in the morning, the alpaca experienced several tonic/clonic convulsions and died. The body was submitted for necropsy. On gross examination, the carcass was in adequate body condition with abundant fat stores. The subcapsular Can Vet J Volume 42, July 2001
surface of the liver showed numerous pale foci, which later, on histological examination, proved to be centrilobular necrosis. Other histological abnormalities included severe widespread, acute to subacute, periacinar hepatocellular necrosis, sinusoidal dilatation, congestion, periacinar lipofuscinosis, and moderate numbers of infiltrated neutrophils. There was marked pigment deposition. The heart had patchy interstitial edema and occasional patches of acute contraction band necrosis. The brain was examined for rabies virus by using an avidin-biotin complex peroxidase and found to be negative. The liver was tested for copper (Cu) 640.5 mg/kg DM (reference range 87.5 to 350 mg/kg DM; toxic concentration 875 to 1400 mg/kg DM) (4), iron 271.25 mg/kg (reference range, 245 to 700 mg/kg), magnesium 595 mg/kg (reference range 392 to 630 mg/kg), zinc 133 mg/kg (reference range, 70 to 315 mg/kg), manganese 6.3 mg/kg (reference range, 7 to 14 mg/kg), and molybdenum (Mo) 6.16 mg/kg (reference range for sheep 1.50 to 6.0 mg/kg). The only significant findings were the high level of liver Cu and high normal level of Mo. Rhodamine staining for Cu was strongly positive in the periacinar regions of the liver. The role of other hepatotoxins associated with the elevated Cu levels in this animal were considered, despite the presence of hepatic lesions typical of Cu toxicity. For example, aflatoxins and pyrrolizidine alkaloids would have produced differing patterns of hepatic necrosis. The tissue levels of iron were normal. The gastrointestinal element of selenium toxicosis was not present, and the absence of histological abnormalities in the kidney helped to rule out lupinosis as a possible hepatotoxin. The ingestion of other poisonous plants is unlikely, despite pasture grazing, due to the feeding of concentrates and alfalfa hay. Retrospectively, the most likely source of Cu in this alpaca was from a 14% commercial pelleted feed containing Cu in a concentration of 18 mg/kg DM with no added Mo, according to the label. Independent analysis (Norwest Laboratories, Winnipeg, Manitoba) of samples taken from the manufacturing plant and 2 samples from the ration consumed by the alpaca revealed Cu levels to be 21.9, 22.6, and 29.3 mg/kg DM, respectively. The forage portion of the diet had been analyzed for its nutritional content but not for Cu or Mo concentrations; however, usual values for the latter are 1 to 4 mg/kg DM (4). Copper toxicity in the camelid, but not in the alpaca, is being reported more frequently. To the authors' knowledge, this is the first reported case of suspected Cu poisoning in the alpaca. Given the severe widespread periacinar hepatic necrosis associated with Cu deposition combined with the lack of other clinical, biochemical, hematological, or postmortem findings, the most likely cause of death was hepatoencephalopathy due to liver failure with Cu as a contributory factor. Camelids, in particular the llama, behave much like sheep with respect to low Cu: deficiencies have been noted to cause flaccid hindlimb paralysis, hypotonia, and hyporeflexia in both the alpaca and the llama (5). In sheep, if the ratios of Cu:Mo exceed 10:1, signs of Cu poisoning typically appear. These include anorexia, weakness, hemoglobinuria, hemoglobinemia, and icterus. Can Vet J Volume 42, July 2001
However, this acute hemolytic crisis has not been described in the llama (6). The lack of these classical signs in the llama makes diagnosing Cu toxicity a challenge. However, nonspecific signs reported in this species include acute anorexia, depression, poor responsiveness, labored breathing, recumbency, and hypothermia (8); all of which were noted in this case. The interaction between Mo and Cu is highly species variable. In the cow, there is significant interaction, whereas, in the pig, there is none at all. The role of Mo in the alpaca is not known and may not be significant. Information regarding the normal hepatic Mo concentrations in the alpaca could not be found, despite an intensive literature search, and the Mo concentrations presented are for the sheep. Tolerance to dietary Cu varies widely among different species (6). Copper toxicity can be the result of a dietary formulation error, mineral imbalance (Cu:Mo ratio), environmental contamination, or abnormal storage and/or excretion (7). Copper poisoning is a complex problem involving many factors, where poisoning can occur on 'nontoxic' dietary intake (8). Copper poisoning has been reported in 4 llamas in a zoological herd (7); it was traced to a high Cu level in the ration (36 mg/kg DM), low Mo level (2.2 mg/kg DM), and a Cu:Mo ratio of 16.6:1. The sensitivity of the camelid to dietary Cu appears similar to that of the sheep, where toxic effects can be appreciated in feed levels above 11 mg/kg DM (9). In this case, despite the label Cu concentration of 18 mg/kg in the commercial pelleted feed, independent analysis revealed concentrations of 21.9 to 29.3 mg/kg DM. Since Mo is not checked for or added by the manufacturer, Cu poisoning from this feed is possible. In the report of Cu toxicity in llamas (7), elevated serum levels of AST, SDH, and GGT were noted. The lack of markedly elevated liver enzymes in this case is puzzling, given the postmortem findings. It has been assumed empirically that these liver enzymes behave similarly in camelids as in other species, but the diagnostic value has not been determined (3). Given that the halflife of these liver enzymes ranges from 3 d to 2 wk, it may be that the liver changes in this case were very acute. In retrospect, serial evaluations of serum liver enzymes after presentation may have shown rising enzyme levels. Liver Cu concentrations in juvenile llamas (6 animals) and adults (5 animals) has been reported (10), noting ranges of 6.7 to 330.0 mg/kg DM and 10 to 36 mg/kg DM, respectively. Other workers (7) found that hepatic Cu levels in adult llama had greater variation, with 4 adults ranging from 340 to 890 mg/kg DM. Toxic hepatic concentrations of Cu in the camelid have been reported (4) occurring from 875 to 1400 mg/kg DM, but this does not differentiate the camel, llama, alpaca, or guanaco. A hepatic Cu concentration of 640.5 mg/kg DM, while significantly above the normal range, is not as high as those previously reported. Liver Cu concentrations vary, where the greater concentration is found in the caudate lobe as compared with other parts (8). It is unknown where the liver sample in this case was taken at postmortem, but Cu levels may have been higher in other parts of the liver. In other species, end stage Cu 555
toxicity results in a sudden release of liver Cu, leading to an acute hemolytic crisis. During this time, serum Cu rises and eventually kidney levels also rise. Since a hemolytic crisis was not observed in this case, or documented in the camelid, the serum Cu may be unreliable. The diagnostic value of this test has also been questioned in other species (6). The normal and toxic levels of Cu and Mo in the alpaca's hepatic tissue, as well as the degree of their interaction, is not known. The liver Cu levels found in the alpaca presented suggest that adults retain Cu at different rates and the interrelationship between Cu, Mo, and sulphur may be more important in the pathogenesis of the disease than the actual levels of Cu. It appears that more work is needed to accurately ascertain the levels at which Cu toxicity and clinical signs are seen in the various species of camelid. In the authors' opinion, an elevated liver Cu concentration of 640.5 mg/kg in this alpaca contributed to cvi its death.
References 1. Hajduk P. Haematological reference values for alpacas. Aust Vet J 1992;69:89-90. 2. Fowler ME, Zinkl JG. Reference ranges for hematologic and serum biochemical values in llamas (Lama glama). Am J Vet Res 1989;50:2049-2053. 3. Garry F. Clinical pathology of llamas. In Johnson LW, ed. Vet Clin North Am Food Anim Pract 1989;5(l):55-69. 4. Puls R. Mineral Levels in Animal Health. 2nd ed. British Columbia: Sherpa Int, 1994:83-109. 5. Andrews AH, Cox A. Suspected nutritional deficiency causing anaemia in llamas (Lama glama). Vet Rec 1997;140:153-154. 6. Smith BP. Large Animal Internal Medicine. 2nd ed. Sydney: Mosby. 1996:1904-1905. 7. Junge RE, Thomberg L. Copper poisoning in four llamas. J Am Vet Med Assoc 1989;195:987-989. 8. Radostits OM, Blood DC, Gay CC. Veterinary Medicine. 8th ed. London: Balliere Tindall, 1994:1495-1499. 9. Martin BJ, Dysko RC, Chrisp CE, Ringler DH. Copper poisoning in sheep. Lab Anim Sci 1988;38:734-736. 10. Ashton DG, Jones DM, Lewis G, Cinderey RN. Some preliminary studies on blood and liver copper levels in ungulates at Whipsnade. Erkrankungen der zootiere. Berlin: Akademie-Verlag, 1979:21, 35-144.
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* Moberg GP, Mench JA, eds. The Biology of Animal Stress: Basic Principles and Implications for Animal Welfare. CABI Publishing, Oxford, 2001, 380 pp, ISBN
* LeGood G, ed. Veterinary Ethics: An Introduction. Continuum Publishing, London, 2000, 218 pp, ISBN 08264-4784-8.
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* World Health Organization. Foodborne Disease: A focus for health education. World Health Organization, Geneva, 2001, 198 pp, ISBN 92-4-156196-3, US$55.80.
* World Health Organization. Evaluation of Certain Veterinary Drug Residues in Food. World Health Organization, Geneva, 2000, 102 pp, ISBN 92-4-1208937, US$18.00. * Macpherson CNL, Meslin FX, Wandeler Al, eds. Dogs, Zoonoses and Public Health. CABI Publishing, Oxford, 2001, 350 pp. ISBN 0-85199-436-9, $US1 10.00.
* Phillips CJC. Principles of Cattle Production. CABI Publishing, Oxford, 2001, 280 pp, ISBN 0-85199-296-X,
$US40.00. * Grandin T, ed. Livestock Handling and Transport, 2nd ed. CABI Publishing, Oxford, 2001, 464 pp, ISBN 0-85199409-1, $US110.00.
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* Catanzaro TE. Promoting the Human-Animal Bond in Veterinary Practice. Iowa State University Press, Ames, 2001, 260 pp, ISBN 0-8138-0382-9, US$36.95. * Lindsay SR. Applied Dog Behavior and Training, Vol. 2: Etiology and Assessment of Behavior Problems. Iowa State University Press, Ames, 2001, 304 pp, ISBN 08138-2868-6, US$44.95.
* Baggot JD. The Physiological Basis of Veterinary Clinical Pharmacology. Iowa State University Press, Ames, 2001, 294 pp, ISBN 0-632-05744-0, US$72.95.
* Bush AO, Fernandez JC, Esch GW, Seed JR. Parasitism: The Diversity and Ecology of Animal Parasites. Cambridge University Press, New York, 2001, 576 pp, ISBN 0-521-66278-X, US$130.00 (hardcover), US$49.95 (softcover).
Can Vet J Volume 42, July 2001
