COPPER TOXICITY IN CATTLE & SHEEP

Transcription

1 COPPER TOXICITY IN CATTLE & SHEEP

2 The talk out line and its aims 1. Background The role of copper Copper deficiency 2. Copper toxicity Clinical signs Diagnosis Main causes 3. To discuss good practice when supplementing copper

3 Functions of copper An essential trace element Required in enzymes, cofactors, reactive proteins e.g. Caeruloplasmin, cytochrome c oxidase, lysyl oxidases, monoamine oxidases, superoxide dismutases, thiol oxidases, tyrosinase Copper deficiency therefore has many different clinical presentations

4 Cytochrome oxidase Storage Lysyl oxidase Superoxidase dismutase All Tissues Liver Tyrosinase Biliary Excretion Bloodstream; Plasma copper Free copper (Loosely bound to albumin) 10-20% (Suttle 2002) Caeruloplasmin 80-90% (Suttle 2002) Via bile 1-5% Rumen + Intestine 95-99% Excreted in faeces

5 Copper antagonists Molybdenum Sulphur Iron Others eg zinc, manganese Insoluble complexes (mainly copper thiomolybdates) form in the rumen and are excreted

6 Copper deficiency

7 No of Diagnoses Sheep in England and Wales with Copper deficiency(513) between Jan and Dec Total Month

8 No of Diagnoses Cattle in England and Wales with Copper deficiency(513) between Jan and Dec SUCKLER REARING Dairy FINISHER Unknown Month

9 Incidents of copper deficiency recorded by AHVLA ( ) 546 diagnoses in beef suckler cattle 0 in dairy cattle 186 in sheep Many forages in Britain are low in available copper so the risk of copper deficiency on unsupplemented diets is relatively high

10 Copper deficiency - prevention Increase copper intake Increase available copper

11 But All chemicals are potential poisons. It is the dose that differentiates a poison from a remedy (Paracelsus )

12 Copper poisoning syndromes 1) Acute parietal Sudden death, collapse Liver necrosis, nephrosis, pleural and peritoneal effusions 2) Acute oral Depression, colic, shock Dysentery and dark urine (haemoglobinuria) if survive 24 hours Gastrointestinal necrosis, haemorrhages, pleural and peritoneal effusions 3) Chronic

13 Chronic copper poisoning Steady rise in liver copper = accumulation phase Liver pathology Increase in liver enzymes (GLDH, AST, GGT, bile acids) No observable rise in plasma copper until copper poisoning imminent

14 Frequency Liver copper results adult dairy cattle VLA 2000 to June Median Mean 8406 StDev 6484 N Liver copper reference range µmol/kg DM Liver copper µmol/kg DM 50000

15 No of Diagnoses Sheep in England and Wales with Copper toxicity(413) between Jan and Dec Copper poisoning in sheep in England & Wales (2002 to December 12th 2011) Total Month

16 No of Diagnoses Incidents of copper poisoning in cattle recorded by AHVLA by purpose Cattle in England and Wales with Copper toxicity(413) between Jan 2002 and Dec Sheep current UNKNOWN SUCKLER REARING OTHER NONE NA MILK FINISHER Month

17 Clinical signs of copper poisoning Acute milk drop Anorexia Malaise Jaundice Tachycardia Dyspnoea Photosensitisation Recumbency Subnormal temperature Brown or cyanotic membranes Red or brown urine

18 Copper toxicity

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20 Copper toxicity

21 Differential diagnosis The clinical symptoms of copper poisoning can be initially confused with other diseases causing similar signs For example: Leptospirosis post parturient haemoglobinuria rape & kale toxicity (SMCO)

22 Diagnosis of copper poisoning - 1 Clinical signs Autopsy Gross observations eg jaundice, haemorrhages, liver necrosis Histology Subacute hepatic degeneration Nephrosis with pigment granules in the tubule cells

23 Diagnosis of copper poisoning - 2 Laboratory testing Elevated liver copper > µmol/kg DM Elevated kidney copper > µmol/kg DM Elevated kidney iron > µmol/kg DM Elevated plasma copper > 50 µmol / l Elevated AST, GGT, GLDH - subclinical liver degeneration occurs in affected herds Haematology - regenerative anaemia

24 Copper toxicity in an 18mo Lleyn ram (2004) Test Units Ref. Range 16 Sept 18 Sept 20 Sept 04 Oct Urea mmol/l Creatinine mmol/l Copper (p) µmol/l AST U/L NT GGT U/L 0-30 NT GLDH U/L 0-25 NT Bilirubin µmol/l 0-7 NT NT 8.2 NT

25 Toxicity in cattle Defra funded a project to investigate copper toxicity in cattle ( )

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27 Herd Profile: Data for 33 herds Herd size All dairy herds 91 % Holstein / Friesian 9 % Jersey Mortality %

28 age (yrs) Cow Profiles for clinical disease > frequency Dry 28% Milking 57% Clinical signs 0-14 days Average duration 2 days

29 frequency 6 5 Level at which prescription required >800mg 4 nk 3 with chel 2 nil chel mgcu/cow/day

30 VLA survey ; results of forage and TMR analysis No evidence of a severe copper antagonist problem on most of the farms Only 2 of 10 forages analysed investigated contained high concentrations of Mo No forages contained high concentrations of S

31 Conclusions main cause of copper toxicity in dairy cows (VLA survey ) Estimated copper intakes >1000mg /day even in absence of known antagonists problem Haphazard use of multiple supplements

32 Summary of possible causes of copper poisoning in cattle and sheep Excessive supplementation Intended or accidental Incidentally related to production Increased bioavailability and absorption of copper Physical and chemical form of copper Low levels of antagonists Decreased copper excretion Pathology Breed traits Increased susceptibility Concurrent oxidative stress Concurrent liver disease

33 Incidentally related to production Increased appetites and milk yield Copper requirement for milk production is low at 0.05mg copper/kg milk. Most copper required for maintenance and growth Given a constant copper concentration in feeding stuffs increased milk yields have increased copper intakes relative to requirements

34 North Ronaldsay sheep grazing seaweed. This diet raises the need for copper and has selected for a breed that utilises copper efficiently. This breed is therefore prone to copper toxicity when grazing normal pastures. Texels & Suffolks also susceptible &? Lleyns. Photograph courtesy of N. Suttle.

35 Treatment Remove concentrates and feed forage There are no licensed products for the treatment of copper poisoning in food producing animals Ammonium tetrathiomolybdate (ATTM) does not meet the prescribing cascade guidelines (Veterinary medicines: product update. Veterinary Record 2010; 167: ) Restrict use of ATTM to valuable breeding stock and ensure that these do not enter the food chain? Oral molybdate, other oral antagonists (Fe, Zn), sulphate (beware toxicity).

36 Good supplementation practice

37 What do we know? EU regulation 1831/2003 sets out the maximum permitted level (MPL) of copper for ruminating cattle at 35mg/kg feed expressed as 88% DM of complete feed this equates to 40mg/kg DM in total diet Greater levels can only be undertaken by written prescription For sheep the MPL is 15mg/kg & if level of copper exceeds 10 mg/kg a warning is required

38 Responsibility It is the responsibility of the farmer and advisors, that the legal maximum levels as described in 1831/2003 are respected Multiple supplementary copper inputs are common on UK farms Individually each input may not be in excess of MPL but in combination, MPL could be exceeded

39 Considerations. Should we feed less copper in the normal dairy cow where antagonists are not present at significant levels? In other countries supplementation levels are lower

40 Copper: total supplemented level Copper levels supplemental level total Germany 3:1 zinc:cu 13 mg/kg DMI 20 mg/kg DMI Ireland mg/kg DMI mg/kg DMI Spain mg/kg DMI mg/kg DMI NL 15 early 10 late lact mg/kg DMI Canada 12 mg/kg 20 mg/kg DMI USA 12 mg/kg 20 mg/kg DMI source Nutreco

41 Good supplementation practice Confirm need for supplementation Blood analysis, liver analysis, post mortem, (dietary analysis) Follow requirements for prescription when supplementing above Feed Regulations limits Monitor efficacy and safety of supplementation

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43 Thank you for your attention

44 Food safety Liver copper concentrations > 500mg/kg WM trigger potential food safety incidents & are reported to the FSA The copper concentrations of milk are relatively stable at approximately 0.05mg copper/kg milk Livers from cull dairy cows frequently do not reach the human food chain Livers from lambs are potentially the most significant source Overall, copper in animal produce is unlikely to be of human toxicological concern