Primary copper poisoning occurs when livestock either ingest or are treated with excessive amounts of copper. Secondary copper poisoning ('toxaemic jaundice') occurs when livestock consume diets with low amounts of copper that under normal circumstances would not cause toxicity. The first circumstance is molybdenum deficiency which occurs especially on lush subterranean clover (Trifolium subterraneum) pastures. This is referred to as phytogenous secondary copper poisoning. Secondly and more commonly, copper toxicity occurs following pyrrolizidine alkaloidosis, exacerbating the sheep's predisposition to accumulating copper in excess of their capacity to excrete it. This is referred to as hepatogenous secondary copper toxicity (Radostits et al.,2007).
It is important to determine the mechanism of copper toxicity in affected flocks to inform future management. In this case a sheep producer near Orange in NSW lost 5% of 3,500 mature composite ewes between lamb marking and weaning in January 2021. The ewes were managed as two separate flocks on properties approximately 10 km apart. One sheep was necropsied on each property. In both cases the cause of death was secondary chronic copper toxicity. One was considered primarily due to phytogenous causes, while the second had liver pathology indicating some hepatogenous contribution.
Ewes at both properties had been grazing abundant subterranean clover (Trifolium subterraneum) dominant pastures for several months prior to recent dry off. Affected ewes had been found dead or were acutely ill, with clinical signs of depression, weakness and recumbency, followed by death. The ewes were generally in good body condition with current vaccination against clostridial diseases and suitable parasite prevention.
The first property was attended on the 13th of January 2021 at time of weaning, following losses of 20 mature ewes from a flock of 1,000. The second property was attended on the 1st of February 2021 at time of shearing, following losses of 150 mature ewes from a flock of 2,500. Dead ewes were not noticed initially because they were difficult to detect in the tall pastures.
A ewe, demonstrating clinical signs of dull mentation, weakness and inability to rise from sternal recumbency, was examined. The ewe was in good body condition, with the only gross abnormality noted being brown to purple tinged mucous membranes. On post-mortem examination subcutaneous and intra-abdominal fat was pale yellow. The liver was diffusely brown. Both kidneys were swollen and black, as shown in Figure 1. The bladder contained brown pigmented urine.
Blood samples were collected from the ewe for haematology and biochemistry. Fixed and fresh samples of the kidney and liver were taken for histopathology and copper level analysis. Pooled faecal samples were taken for faecal egg count (FEC).
A ewe was noticed standing separate to the mob with a dull demeanour. It became recumbent and died several hours later. Post-mortem examination showed the ewe was in fair condition. Mucous membranes were pale purple to brown. The trachea contained coagulated blood in the distal quarter and a small amount of mucus in the cranial portion. The lungs were diffusely brown-tinged. The thyroid glands were mildly enlarged. Intra-abdominal fat was moderately icteric. The liver appeared grossly normal with some possible localised thickening. Kidneys were black and swollen, with loss of normal architecture. The abomasal mucosa was mildly erythematous.
Samples collected from the ewe included fixed samples of liver, kidney, thyroid and lung for histopathology, fresh kidney and liver samples for copper level analysis and a faecal sample for FEC.
The noteworthy haematology and biochemistry results from blood collected at property 1 were: elevated liver enzymes consistent with hepatocellular injury, moderate hyperbilirubinaemia, marked azotaemia, moderate leucocytosis with neutrophilia, mild elevation in creatine kinase and a mildly elevated serum copper concentration.
Liver samples from both properties had evidence of hepatocellular degeneration and necrosis, with hepatocytes and macrophages containing brown pigment indicative of copper accumulation. The sample from property 1 indicated there were minimal chronic changes indicative of exposure to hepatotoxic plants such as pyrrolizidine alkaloids. However, comments regarding the sample collected at property 2 indicated that there were clear changes consistent with exposure to pyrrolizidine alkaloids which may have contributed to the chronic copper toxicosis.
Kidney samples from both properties demonstrated evidence of acute, severe tubular injury and necrosis. The lung sample collected at property 2 indicated multifocal oedema with no other significant findings. The thyroid sample was unremarkable.
Tissue copper levels
Liver and kidney samples from both properties contained markedly elevated copper levels.
|Kidney copper levels||Liver copper levels|
|(0.00 - 0.20 mmol/kg wet weight)||(0.23 - 3.67 mmol/kg wet weight)|
|Property 1||0.82 mmol/L||7.87 mmol/L|
|Property 2||1.09 mmol/L||6.59 mmol/L|
Faecal egg count
Faecal samples from both properties were negative for Strongyle and Nematodirus eggs, tapeworm and coccidia.
Findings from both properties are consistent with an acute haemolytic crisis secondary to chronic copper accumulation.
This case is consistent with chronic secondary copper toxicity. However, histopathological analysis of the liver samples from the two properties differed; the sample from property 1 demonstrated no chronic change associated with hepatotoxic plant exposure, indicating a phytogenous copper toxicity. However, liver samples from property 2 demonstrated karyomegaly of hepatocytes, a change consistent with hepatotoxic plant exposure indicating a hepatogenous component (Gupta, 2019). These histological changes were present without gross pathology; typically, sheep with chronic toxin exposure have a shrunken, fibrotic liver (Abbott, 2018).
Common or European heliotrope (Heliotropium europaeum), blue heliotrope (Heliotropium amplexicaule) and Paterson's curse (Echium plantagineum) contain hepatotoxic pyrrolizidine alkaloids (PA) and are endemic throughout much of the Central Tablelands region of NSW (Gupta, 2019; NSW Department of Primary Industries, 2020). Both properties have well-managed, perennial pastures so it is unlikely that they were exposed to significant quantities of these plants. They were also previously fed hay and grain in a drought lot where exposure to plants containing PA was again unlikely.
The ewes on both properties were grazing subterranean clover (Trifolium subterraneum) dominant pastures in months prior to this event which are typically low in molybdenum and relatively high in copper. Cases of chronic copper toxicity in sheep grazing clover have been described in south-eastern Australia before (Keast 1954, Anon 1956,). Classically, copper accumulates to toxic levels throughout winter and spring when the copper to molybdenum ratio increases. The ratio typically equilibrates during late spring and summer as pastures dry off. However, incidence is sporadic and there is much seasonal variation (Abbott, 2018). Given the higher than average levels of rainfall over the past 12 months in the Central Tablelands, the occurrence of a phytogenous copper toxicity outbreak in summer is conceivable.
Management strategies to prevent further losses in this flock include administering molybdenum and sulphur solutions to decrease the copper load in the liver. This can be done via drenching, spraying solution on feed or provision of lick blocks. Drenching is the most reliable way to provide an adequate dose to every individual, though is more stressful to the sheep. While stress is a recognised catalyst for development of an acute haemolytic crisis in copper poisoned sheep, delaying treatment under the rationale of reducing the associated stress of mustering and treating may be a false economy (Abbott, 2018).
Once a sheep enters the haemolytic phase of toxicity, characterised by sudden release of copper from the liver and acute illness, the prognosis is poor. Thus, focusing on prevention of asymptomatic animals is vital (Osweiler, 2015). The hepatic damage from PA ingestion is irreversible and any stock affected will be predisposed to copper toxicity henceforth (Abbott, 2018). As there is evidence of subclinical PA hepatopathy in this flock, mitigation of potential phytogenous toxicity is even more important.
Long term strategies could involve improving pasture diversity and providing molybdenum supplements to sheep while grazing at-risk pastures. However, care must be taken to not induce a copper deficiency via overzealous molybdenum provision. Research by Minervino et al., (2018) indicates dietary zinc supplementation could be an alternative to this, finding that 300mg/kg dry matter daily is effective in preventing hepatic copper accumulation in sheep grazing copper-rich pastures and is well tolerated.
Outbreaks of acute illness and mortality due to chronic copper toxicity can take producers by surprise, as documented in this case where apparently healthy, mature ewes were affected. Awareness and management strategies are vital to protecting flocks from significant losses.