What if copper required for in the body?
- Required-enzymes:
- For Iron metabolism and mitochondrial function
- Multiple-copper oxidases for Iron transport
- Superoxide dismutase
- Cytochrome c oxidase
- For Iron metabolism and mitochondrial function
What species are most at risk for copper toxicity?
- All species affected
- Sheep most at risk
What are sources of copper for ruminants?
- Dietary supplements
- Water
- Disinfectants
- Mineral blocks
- Cu/Mo/S interactions
What common practices in cattle raising put animals at risk for copper toxicity?
- Feeding poultry litter
- rations > 100 ppm Cu
- Swine rations > 2000 ppm Cu in weaning diets
- Sheep rations > 15 ppm cu
What causes acute copper toxicosis in ruminants? What are the symptoms?
- Causes: Drenches, foot baths
- Symptoms:
- Diarrhea
- Liver Damage
- Shock
What other toxicities resemble Acute Cu poisoning?
- Arsenic
- Iron
- Selenium
Why are sheep so sensitive to chronic Cu toxicosis?
- Sheep are sensitive to elevated feed levels
- >15 ppm Cu predisposes to Cu accumulation
- Sheep have low G-6-PD activity (erythrocyte health)
- highly sensitive to Cu induced hemolysis
What are the steps in Chronic Cu toxicosis for sheep?
- Accumulation phase:
- Over weeks to months
- Cu stored in liver (lysozymes)
- No clinical effects except slight decrease in rate of gain
- Acute Hemolytic Crisis:
- After release of Cu from the liver (stress trigger)
- Animals are depressed, anorectic, weak, hemoglobinuria, icteric
- oxidative stress
What lesions does Cu toxicosis cause in sheep?
- Icterus (mucous membranes, body fat)
- Yellow friable liver
- Dark to black kidneys
- Gun metal blue kidneys - Hb nephrosis
- Dark and red serum and urine
- Methemaglobinemia
- from oxidative effect of free Cu
How is Cu toxicosis diagnosed in sheep?
- Hx, Clinical signs
- Gross lesions - icterus and black kidneys
- Liver >150 ppm Cu wet wt (20-100)
- Kidney > 15 ppm Cu wet wt (4-10)
- Serum >1.5 - 2 ppm Cu
- Cu and Mo in feed - other rations
- Cu from all sources is ADDITIVE
How is Cu toxicosis in sheep treated?
- Individual animal - very guarded prognosis
- D penicillamine (52 mg/kg/day)
- increases Cu excretion
- Supportive care
- Prognosis depends on kidney function
- TTM (tetrathiomolybdate) used in UK, not approved or commercially available in the US
- Flock:
- Eliminate sources of Cu
- Na molybdate (100 mg/hd/day) in feed for 3 weeks (10lbs of a 2% premix/ton)
- Not as a drench, too much stress
- Ground gypsum (calcium sulfate) 5 lb/ton of feed for 3 weeks
- ZnO at 100-200 ppm reduces Cu absorption
How can Cu toxicosis in sheep be prevented?
- Producer + feed supplier education
- Use only supplement formulated for Sheep
- Cattle products have too much copper
- Evaluate Cu, Mo, and S in diet
- Grain, forages, minerals, water, mineral blocks
What is Canine Copper Storage Disease?
- Familial, associated with specific breeds
- West highland White
- Dalmatian
- Doberman
- Labrador
- Chronic accumulation, first noted in young adults
- Manifest as chronic hepatopathy and/or acute icterus
- Associated with reduced liver function
What is Bedlington terrier Cu Toxicosis?
- Described in 1975
- Autodomal recessive mutation in COMMD1
- Well characterized
- Progressive liver disease
- Clinical state correlates with Cu load
What signs of Cu toxicosis do young dogs (<6yrs) exhibit?
- Anorexia
- Vomiting
- Weakness
- Lethargy
- Dehydration
- Polyuria, polydipsia
- Icterus
- Coagulopathy
What lesions does Cu toxicosis cause in dogs
- Hepatomegaly or microhepatica
- Prominent cytoplasmic granules in hepatocytes
- Focal hepatitis / focal cirrhosis / chronic, active hepatitis
- Generalized cirrhosis
What is the most common cause of chronic hepatitis?
copper
How is Canine Copper Storage Disease diagnosed?
- Breed - Bedlington terrier, West highland white, Skye terrier
- autosomal recessive abnormal biliary excretion
- Lesions:
- Liver biopsy + Cu concentration usually of greater than 1500 ppm on a dry weight basis and frequently over 2000 ppm
- Increased ALT occurs late and reflects hepatocellular injury
- Also elevated GGT, bilirubin, PT, anemia
- Generally no increase in serum Cu in affected dogs
What is the normal liver Cu in dogs?
on a dry wt basis 90 - 350 ppm
How is Canine Copper Storage Disease treated?
- Penicillamine (Cuprimine®)
- Chronic administration 10-15 mg/kg PO q 12h
- Zinc supplements
- Glucocorticoids for lysosomal stabilization in acute disease
- Ascorbic acid, 500- 1000 mg/day to enhance urinary excretion of Cu
- 2, 3, 2 - tetramine (15 mg/kg PO q12h) has been used as a chelator for Cu in Bedlington terriers
- Vit E (200 - 600 IU q24h) for oxidative liver damage
Summary: What does occasional acute copper poisoning do?
Serious GI and hepatic damage
Summary: What does Chronic copper poisoning do?
- Chronic icterus / hemoglobinuria / black kidneys in sheep
- Closely associated with Mo and SO4
Summarize the diagnosis and treatment of Canine Copper storage disease?
- Dx: based on C/S, liver Cu, NOT serum
- Tx: based on chelation and mineral competition
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Intro to Toxicology24
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Introduction to Metals80
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Rodenticides60
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At home poisonings79
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Op/Carbamates/pyrethrins30
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Malicious poisoning0
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Toxicosis Patient management18
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Bovine Nitrate Poisoning13
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Sulfur-Associated Polioenephalomalacia9
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NPN & Ammoniated Feeds15
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Mycotoxins46
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Gossypol9
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selenium24
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copper23
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Molybdenum & Zinc15
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Ionophores & B-agonist35
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Sodium ion Toxicosis11
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Exam 2 Objectives0
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Decontamination of Poisoned patients5
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Toxic Gases50
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Drinking Water26
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LA Toxic Plants29
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Blue Green Algae12
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SA Toxic Plants0
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Venoms and Poisons0
