copper

Question 1

What if copper required for in the body?

Answer 1

• Required-enzymes:
  
  • For Iron metabolism and mitochondrial function
    
    • Multiple-copper oxidases for Iron transport
    • Superoxide dismutase
    • Cytochrome c oxidase

Question 2

What species are most at risk for copper toxicity?

Answer 2

• All species affected
• Sheep most at risk

Question 3

What are sources of copper for ruminants?

Answer 3

• Dietary supplements
• Water
• Disinfectants
• Mineral blocks
• Cu/Mo/S interactions

Question 4

What common practices in cattle raising put animals at risk for copper toxicity?

Answer 4

• Feeding poultry litter
  
  • rations > 100 ppm Cu
• Swine rations > 2000 ppm Cu in weaning diets
• Sheep rations > 15 ppm cu

Question 5

What causes acute copper toxicosis in ruminants? What are the symptoms?

Answer 5

• Causes: Drenches, foot baths
• Symptoms:
  
  • Diarrhea
  • Liver Damage
  • Shock

Question 6

What other toxicities resemble Acute Cu poisoning?

Answer 6

• Arsenic
• Iron
• Selenium

Question 7

Why are sheep so sensitive to chronic Cu toxicosis?

Answer 7

• 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

Question 8

What are the steps in Chronic Cu toxicosis for sheep?

Answer 8

• 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

Question 9

What lesions does Cu toxicosis cause in sheep?

Answer 9

• 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

Question 10

How is Cu toxicosis diagnosed in sheep?

Answer 10

• 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

Question 11

How is Cu toxicosis in sheep treated?

Answer 11

• 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

Question 12

How can Cu toxicosis in sheep be prevented?

Answer 12

• 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

Question 13

What is Canine Copper Storage Disease?

Answer 13

• 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

Question 14

What is Bedlington terrier Cu Toxicosis?

Answer 14

• Described in 1975
• Autodomal recessive mutation in COMMD1
• Well characterized
  
  • Progressive liver disease
  • Clinical state correlates with Cu load

Question 15

What signs of Cu toxicosis do young dogs (<6yrs) exhibit?

Answer 15

• Anorexia
• Vomiting
• Weakness
• Lethargy
• Dehydration
• Polyuria, polydipsia
• Icterus
• Coagulopathy

Question 16

What lesions does Cu toxicosis cause in dogs

Answer 16

• Hepatomegaly or microhepatica
• Prominent cytoplasmic granules in hepatocytes
• Focal hepatitis / focal cirrhosis / chronic, active hepatitis
• Generalized cirrhosis

Question 17

What is the most common cause of chronic hepatitis?

Answer 17

copper

Question 18

How is Canine Copper Storage Disease diagnosed?

Answer 18

• 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

Question 19

What is the normal liver Cu in dogs?

Answer 19

on a dry wt basis 90 - 350 ppm

Question 20

How is Canine Copper Storage Disease treated?

Answer 20

• 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

Question 21

Summary: What does occasional acute copper poisoning do?

Answer 21

Serious GI and hepatic damage

Question 22

Summary: What does Chronic copper poisoning do?

Answer 22

• Chronic icterus / hemoglobinuria / black kidneys in sheep
• Closely associated with Mo and SO₄

Question 23

Summarize the diagnosis and treatment of Canine Copper storage disease?

Answer 23

• Dx: based on C/S, liver Cu, NOT serum
• Tx: based on chelation and mineral competition