Copper toxicity in a New Zealand dairy herd

Chronic copper toxicity was diagnosed in a Jersey herd in the Waikato region of New Zealand following an investigation into the deaths of six cattle from a herd of 250 dry cows. Clinical signs and post-mortem examination results were consistent with a hepatopathy, and high concentrations of copper in liver and blood samples of clinically affected animals confirmed copper toxicity. Liver copper concentrations and serum gamma-glutamyl transferase activities were both raised in a group of healthy animals sampled at random from the affected herd, indicating an ongoing risk to the remaining cattle; these animals all had serum copper concentrations within normal limits. Serum samples and liver biopsies were also collected and assayed for copper from animals within two other dairy herds on the same farm; combined results from all three herds showed poor correlation between serum and liver copper concentrations.To reduce liver copper concentrations the affected herd was drenched with 0.5 g ammonium molybdate and 1 g sodium sulphate per cow for five days, and the herd was given no supplementary feed or mineral supplements. Liver biopsies were repeated 44 days after the initial biopsies (approximately 1 month after the end of the drenching program); these showed a significant 37.3% decrease in liver copper concentrations (P <0.02). Also there were no further deaths after the start of the drenching program. Since there was no control group it is impossible to quantify the effect of the drenching program in this case, and dietary changes were also made that would have depleted liver copper stores.Historical analysis of the diet was difficult due to poor record keeping, but multiple sources of copper contributed to a long term copper over supplementation of the herd; the biggest source of copper was a mineral supplement. The farmer perceived this herd to have problems with copper deficiency prior to the diagnosis of copper toxicity, so this case demonstrates the importance of monitoring herd copper status regularly. Also the poor correlation between liver and serum copper concentrations in the three herds sampled demonstrates the importance of using liver copper concentration to assess herd copper status.     

Enzootic ataxia and caprine arthritis/encephalitis virus infection in a New England goat herd [corrected

Ataxia was diagnosed in kids from a New England goat herd. Concurrent infection with the caprine arthritis/encephalitis (CAE) virus contributed to the development of hind limb ataxia and weakness in one of the kids. Six kids from this herd had signs of hind limb ataxia and paralysis. Detailed evaluation of 2 of the affected kids revealed low liver and serum copper concentrations and spinal cord demyelination. One kid also had histologic changes in the CNS and lungs, compatible with a diagnosis of CAE. Serum copper concentration was determined in affected goat kids and their dams and was compared with serum copper concentration in clinically normal kids and their dams from the same herd. Serum copper concentration also was measured in dams and kids in a control herd that had no history of ataxia. The mean serum copper concentration in affected kids was 0.125 microgram/ml, compared with 0.45 microgram/ml in unaffected kid herdmates. Kids from the control herd had mean serum copper concentration of 0.6 microgram/ml. Mean serum copper concentration in dams of kids with neurologic signs also was low (0.25 microgram/ml), compared with that (0.5 microgram/ml) in dams of clinically normal kids of the affected herd and that (0.95 microgram/ml) in dams of kids of the control herd. Results of a serologic survey (by use of agar gel immunodiffusion) of the affected herd for CAE indicated that 69.5% of the goats were seropositive. Dietary copper intake was determined to be adequate in this goat herd; therefore, copper deficiency appeared to be conditioned by an interfering substance. However, a search for interfering substances was unrewarding.     

Chronic copper toxicity in a dairy herd

The addition of excessive copper to a commercially prepared dairy ration caused chronic copper toxicity in a dairy herd. A formulation error by a feed company resulted in copper levels of 800 to 1,000 mg/kg in the “as fed concentrate,” amounting to about 400-500 mg copper/kg of the whole ration. Five animals died with typical signs of acute copper toxicity, including intravascular hemolysis and methemoglobinemia. A further 39 cows died on the farm from a combination of debilitation and secondary infectious causes, and 215 were sent to slaughter because of debilitation and poor milk production. The mortality of calves born to dams that had been fed the toxic concentrate was approximately 50%.

We postulate that dairy cows, particularly pregnant cows, may be more susceptible to copper toxicity than other cattle, and suggest reexamination of the presently allowable maximum levels of copper supplementation of diets for dairy cattle.

     

Copper toxicosis in a dairy goat herd

CASE DESCRIPTION: A closed herd of 400 mixed-breed dairy goats was examined because of a decrease in milk production and increase in mortality rate. Nine animals had died within a 1-month period. CLINICAL FINDINGS: Clinical signs were evident only in lactating goats and included anorexia and recumbency. In the most severely affected goats, signs progressed to neurologic abnormalities and death. Serum aspartate aminotransferase activity, gamma-glutamyltransferase activity, and total bilirubin concentration were high in clinically affected does, but no evidence of hemolysis was found. A diagnosis of copper toxicosis was made on the basis of high liver and kidney copper concentrations and histologic evidence of hepatic necrosis. Goats were found to have been fed a mineral mix containing 3,050 ppm copper for 9 months prior to the onset of copper toxicosis. Overall, there was no consistent relationship between serum hepatic enzyme activities, serum copper concentration, and liver copper concentration. TREATMENT AND OUTCOME: Clinically affected goats were treated with penicillamine, ammonium molybdate, sodium thiosulfate, and vitamin E. Penicillamine increased urine copper excretion in treated does versus untreated control animals. An increased incidence of infectious disease was identified in the herd 9 months later. Liver vitamin E concentration was low in 10 of the 12 goats that underwent necropsy. CLINICAL RELEVANCE: Findings suggested that penicillamine may be an effective treatment for goats with copper toxicosis. Production losses months after the diagnosis was made suggested that the intoxication had a prolonged animal welfare and economic impacts.     

Treatment of chronic copper poisoning in dairy sheep with oral ammonium molybdate and sodium sulphate

Four weeks after the introduction of a new ration, a herd of sheep in the Swiss midland area was affected by depression, anorexia, decreased milk production, anemia, hemoglobinuria and frequent recumbency. Seventeen ewes died within a few days. A diagnosis of chronic copper poisoning was based on the results of feed analysis, histopathological findings and the toxicological examination of liver tissue. The remaining sheep were treated with oral ammonium molybdate and sodium sulfate, which together provide an inexpensive alternative to the chelator D-penicillamine.This combination not only prevents further copper intake, but also supports its elimination from the hepatocellular storage compartments. Serum copper levels have been determined to monitor the mobilization of copper following this antidote therapy.     

Minimal herd sample size for determination of blood copper status of cattle

Copper is required by cattle for synthesis of numerous proteins and enzymes. Copper deficiency in cattle results in a variety of signs ranging from weight loss to diarrhea. In the fall of 1984 and 1985, blood samples were collected from 22 cattle herds near Gunnison, Colo. Approximately one third of the herds were classified as copper deficient (ie, mean serum copper concentration less than 0.6 mg/L). The inherent variability of serum copper concentrations within a herd mandates the determination of the minimal number of cattle to be tested to properly assess the blood copper status of a herd. Coefficients of variation for serum copper concentration were used to calculate a minimal sample size, with a 95% confidence interval for each herd. Minimal sample size ranged from 3 to 55 cattle/herd (ie, 1 to 22% of the herd); this finding suggested that the usual procedure of testing 10% of the herd may be inappropriate.     

Copper deficiency in a herd of captive muskoxen.

At necropsy, a mature muskox cow was found to have exceedingly low serum and liver copper concentrations of 4.8 = mumol/L and 0.02 mmol/kg, respectively. Serum copper levels were also low in remaining members of the herd but returned to normal after parenteral treatment with calcium copper edetate.     

Loss of reserves of Cu in liver when Cu supplements are withdrawn from dairy herds in the Waikato region

Abstract

AIM: To monitor the consequences of withdrawing mineral Cu supplements from two dairy herds with initially high concentrations of Cu in liver.

METHODS: Two herds were selected from dairy farms in the Waikato region of New Zealand that participated in an earlier survey of Cu supplementation practices and Cu status of dairy cows. The herds were fed pasture, grass and maize silage, plus palm kernel expeller (PKE) containing 25–30 mg Cu/kg dry matter (DM) fed at 2–4 kg/cow/day. No mineral Cu supplements were supplied from January 2009. Pasture samples were collected for mineral analysis in September 2008 and April 2009. Concentration of Cu in liver biopsies from the same 9–10 cows per herd was measured on three occasions between April 2009 and May 2010.

RESULTS: Pastures on both farms contained 10 mg Cu/kg DM, 0.1–0.5 mg Mo/kg DM and 3.5–4.0 g S/kg DM. The initial herd mean concentrations of Cu in liver were 1,500 (SD 590) and 1,250 (SD 640) μmol Cu/kg fresh tissue. In the absence of mineral Cu supplements, those mean concentrations decreased over 12 months to 705 (SD 370) and 1,120 (SD 560) μmol Cu/kg fresh tissue, respectively. For cows in the first herd, the rate of depletion of liver Cu reserves was influenced by initial concentration of Cu, such that high concentration led to faster loss according to first-order kinetics.

CONCLUSIONS: Mineral Cu supplementation was not necessary over 12 months for two dairy herds with mean concentrations of Cu in liver >1,250 μmol Cu/kg fresh tissue, grazing pastures containing 10 mg Cu/kg DM and concentrations of Mo <1 mg/kg DM. The quantity and particularly the duration of feeding PKE appeared to be a factor in whether or not the herd lost substantial reserves of Cu in liver during the year. However, the Cu status of both herds in this study was more than adequate to support late pregnancy and mating.

CLINICAL REVELANCE: Copper status of the herd should be monitored and on-farm management of Cu nutrition should take into account all sources contributing to daily intake of Cu. Where Cu supplementation has been excessive and there is risk of chronic Cu toxicity, mineral Cu supplements may be withdrawn for a period commensurate with the expected rate of liver Cu depletion.     

Failure of zinc supplementation to prevent severe facial eczema in cattle fed excess copper

CASE HISTORY: A 400-cow dairy unit in the Waikato suffered a severe outbreak of facial eczema (FE) despite consistent zinc supplementation and significantly elevated serum zinc concentrations. CLINICAL FINDINGS: FE prevention had begun in mid-January 2006, via zinc sulphate supplementation in the water. Photosensitisation was reported on 06 April, contemporaneous with a marked increase in the number of Pithomyces chartarum spores in pasture samples. Within 10 days of this first clinical case, 100 affected cows had been dried off, eight of which subsequently died or were culled. Blood samples were collected from ten affected cows; all had serum zinc concentrations >17 micromol/L, and eight had gamma-glutamyl transferase (GGT) activities >200 U/ml, indicating that the photosensitisation was secondary to liver damage, i.e. probably FE. Further investigation identified that this herd had been receiving excess copper supplementation; 4/6 culled cows had liver copper concentrations within or above the marginal range for copper toxicity. DIAGNOSIS: Severe FE despite zinc supplementation that increased serum zinc concentrations above recommended levels. CLINICAL RELEVANCE: As zinc supplementation significantly reduces apparent copper status, copper supplementation is often used to counteract this. Previous excess copper intake may reduce the efficacy of zinc in preventing FE, thus copper intake should be assessed prior to the start of zinc supplementation.     

Suspect copper toxicity in an alpaca

An alpaca presented in lateral recumbency and subsequently died. On necropsy 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.     

Hemoglobinuria in a dairy herd. (A short report)

This paper reports about the occurrence of hemoglobinuria in a herd of grazing dairy cows. Laboratory findings of serum, liver, pasture and soil showed hypocuprosis in this herd. Copper supplementation results in clinical recovery. Possible pathogenetic relations between copper deficiency and hemolytic anaemia are discussed.     

Case study of copper poisoning in a British dairy herd

Following the initial diagnosis of chronic copper poisoning (CCP), the copper (Cu) status of a British dairy herd was investigated. Eight fatal cases of CCP were identified over a 17-month period, from December 1999 to May 2001, involving seven Jersey cows and one Holstein-Friesian; seven cows were dry when CCP occurred. Case diagnostic criteria were necrotising hepatopathy associated with abnormally high liver and kidney Cu concentrations. Analysis of the ration for the high-yielding Jersey cow group revealed about 50 mg Cu/kg dry matter intake (DMI). Risk factors predisposing to fatal CCP were Jersey breed, previous high yield, first two weeks of the dry period and moderately high dietary Cu (greater than 40 mg Cu/kg DMI).     

Failure of zinc supplementation to prevent severe facial eczema in cattle fed excess copper

CASE HISTORY: A 400-cow dairy unit in the Waikato suffered a severe outbreak of facial eczema (FE) despite consistent zinc supplementation and significantly elevated serum zinc concentrations.

CLINICAL FINDINGS: FE prevention had begun in mid-January 2006, via zinc sulphate supplementation in the water. Photosensitisation was reported on 06 April, contemporaneous with a marked increase in the number of Pithomyces chartarum spores in pasture samples. Within 10 days of this first clinical case, 100 affected cows had been dried off, eight of which subsequently died or were culled. Blood samples were collected from ten affected cows; all had serum zinc concentrations >17 µmol/L, and eight had gamma-glutamyl transferase (GGT) activities >200 U/ml, indicating that the photosensitisation was secondary to liver damage, i.e. probably FE. Further investigation identified that this herd had been receiving excess copper supplementation; 4/6 culled cows had liver copper concentrations within or above the marginal range for copper toxicity.

DIAGNOSIS: Severe FE despite zinc supplementation that increased serum zinc concentrations above recommended levels

CLINICAL RELEVANCE: As zinc supplementation significantly reduces apparent copper status, copper supplementation is often used to counteract this. Previous excess copper intake may reduce the efficacy of zinc in preventing FE, thus copper intake should be assessed prior to the start of zinc supplementation.     

Histochemigal Detection of Copper in the Liver from Sheep Chronically Poisoned by Copper

Continued ingestion of copper in excess of the nutritional requirement leads in all animals to its passive accumulation within the tissues, especially the liver. Up to certain levels varying greatly with the species high concentrations of copper in the liver appear to impose no physiological hardship on the animal. Above these levels there may occur a catastrophic liberation of a high proportion of the copper into the blood stream resulting in extensive hemolysis and jaundice usually followed by death. Sheep are more prone to the hemolytic crisis of chronic copper poisoning than other animal species. The hemolytic crisis of chronic copper poisoning is associated with centrolobular necrosis of the liver. The copper concentration in the liver is usually 300 p.p.m. or more (wet tissue) compared with about 50 p.p.m. in normal sheep (Simesen & Møller 1969).     

Using sodium molybdate to treat chronic copper toxicity in dairy cows: A practical approach

Abstract

CASE HISTORY: A Jersey herd of 350 cows and 70 heifers located in the Taranaki region of New Zealand ceased milking in June 2011. Ten cows died during the subsequent 14 days. For at least 9 months, the cows had received palm kernel expeller (PKE) and molasses supplements. Additional Cu supplementation was provided through the water system. Total Cu intake was calculated to be 400?mg/day/cow.

CLINICAL AND PATHOLOGICAL FINDINGS: Half of the cows died suddenly while others presented with anorexia, depression and ataxia, which progressed to recumbency and death after 1 to 3 days. Clinical signs were mild dehydration, cyanosis and firm faeces which were covered in dark blood. Mean concentrations of Cu in liver and kidney in three of the dead cows were 3,900 and 440?µmol/kg fresh weight (FW), respectively. Haemorrhages were observed throughout the alimentary tracts and in muscles, and there were ecchymotic haemorrhages on the epi- and endocardia. The livers were swollen and the gall bladder walls were inflamed.

DIAGNOSIS: High concentrations of Cu in the liver and kidney are characteristic findings of chronic Cu toxicity.

TREATMENT: The remaining herd was fed 200?mg Mo, as sodium molybdate, per cow per day and all Cu supplements were removed including those provided by the water supply. This reduced mean concentrations of Cu in liver from 3,100 to 1,320?µmol/kg FW within 26 days in the five live animals that were biopsied. There were no further deaths.

CLINICAL RELEVANCE: In dairy herds where excessive Cu intakes have resulted in high liver Cu concentrations and caused chronic Cu toxicity, the removal of all Cu supplements and provision of high intakes of Mo (200?mg/cow/day) can markedly reduce liver Cu stores within 4 weeks.     

Safety and effectiveness of cupric oxide particles for increasing liver copper stores in cattle

Five groups of three or four crossbred steers, mean initial liveweight 220 kg, were given a diet of barley and hay ad libitum. Each animal received a single oral dose of 0, 5, 10, 20 or 40 g cupric oxide particles. A dose of 5 g cupric oxide particles increased liver copper stores for about 240 days and higher doses increased liver stores for longer but 40 g was no more effective than 20 g (85 mg kg-1 liveweight). Variation among individuals was marked but the highest liver copper concentration recorded (7.59 mmol kg-1 dry matter) produced no biochemical evidence of copper toxicity. Earlier, cupric oxide particles were separated into three fractions, clumps, short rods and long rods and 5 mg kg-1 liveweight of each fraction given to steers of 173 kg mean liveweight. The form of the particles did not affect either their retention in the alimentary tract or the accumulation of copper in the liver.     

PREVENTION OF OVINE LUPINOSIS BY THE ORAL ADMINISTRATION OF ZINC SULPHATE AND THE EFFECT OF SUCH THERAPY ON LIVER AND PANCREAS ZINC AND LIVER COPPER

Three experiments were carried out using Merino wethers to investigate if oral administration of zinc sulphate would provide protection against the liver damage that occurs in lupinosis. At the same time, the effect of this zinc therapy on liver and pancreas zinc, and liver copper concentrations, was studied.
The zinc therapy caused increases in liver and pancreas zinc concentrations, and a drop in the liver copper concentration. Adminstration of the toxins of Phomopsis leptostromiformis with the zinc increased the magnitude of these changes.
Administration of 0.5 g zinc or greater per day, as zinc sulphate, reduced the liver damage caused by the toxins of P. leptostromiformis. The degree of liver protection provided by the zinc therapy varied both between animals within treatments and between treatments in different experiments. Zinc toxicity was encountered.     

Haemolytic crisis in sheep as a result of chronic exposure to copper

Usually practicing veterinarians and animal keepers have to deal with inadequate supplementation of copper which causes deficiency diseases. However, instead of curing, the consequential intake of copper is likely to cause copper intoxication. Copper poisoning is observed particularly frequently, in sheep--the most sensitive domestic animal to copper toxicity. In most cases, sheep undergo chronic exposure to copper causing liver necrosis and resulting in massive haemolysis, haemoglobinuria and eventually in renal failure. The observed symptoms have an acute character and a set of them is called haemolytic crisis. The pathogenesis, signs and diagnosis of this syndrome are described in this article.     

Sensitivity and specificity of serum copper determination for detection of copper deficiency in feeder calves

OBJECTIVE: To determine the relationship between serum and liver copper concentrations and evaluate serum copper determination for diagnosis of copper deficiency in juvenile beef calves. DESIGN: Cross-sectional study. ANIMALS: 105 juvenile beef calves. PROCEDURE: Copper concentrations were measured in paired liver and serum samples from 6- to 9-month-old beef calves. Regression models that predicted liver copper concentration as a function of serum copper concentration were developed. Sensitivity and specificity of serum copper concentration for detection of low liver copper concentration were determined, using a range of serum copper concentrations as test endpoints. Positive and negative predictive values were calculated. RESULTS: The association between serum and liver copper concentrations was significant; however, regression models accounted for only a small portion of the variation in liver copper concentrations. For a serum copper concentration endpoint of 0.45 microg/g, sensitivity and specificity for detection of low liver copper concentration were 0.53 and 0.89, respectively. Positive and negative predictive values of serum copper concentration for detection of low liver copper concentration ranged from 0.37 to 0.85 and 0.63 to 0.94, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Regression models are inappropriate for predicting copper status as a function of serum copper concentration. Serum copper concentration is fairly specific for detection of low liver copper concentration but only marginally sensitive when serum copper concentration of 0.45 microg/g is used as a test endpoint. The value of serum copper concentration as a diagnostic indicator depends on prevalence of copper deficiency.     

Changes in the concentrations of bile acids in the plasma of sheep with liver damage

The concentration of total plasma bile acids was measured in normal sheep and in sheep in which liver damage was induced by chronic copper poisoning, ligated bile ducts or induced ketosis. All three treatments produced a rise in total bile acid concentration in plasma which was proportional to the degree of hepatic damage seen histologically and which tended to parallel changes in activity of iditol, and glutamate dehydrogenase and aspartate amino-transferase in plasma. Plasma bile acid concentration was a more sensitive method of detecting these types of liver damage than was the measurement of total plasma bilirubin concentration, and could be used to assess alterations in liver function in sheep.