COPPERCopper is an essential trace element that catalyses various processes in heme synthesis and iron absorption. It acts as a co-factor in the function of cellular enzyme such as Tyrosinase Cytochrome Oxidase, Dopamine-beta-hydroxylase and preoxidases.Copper has interrelationship with elements such as Molybdenum and Sulphur.

Properties:Copper occupies a position between Nickel and Zinc in group 1B of the Periodic table.

Copper exists in three oxidisation states they are: metallic copper (0), cuprous ion (+1, monovalent) and cupric ion (+2, divalent).

Copper is a strong oxidising agent.

Source of Toxicity:Acute toxicity : due toContamination of food and water. Excessive use of copper in agricultural and veterinary practices.Chronicity toxicity:Genetic susceptibility and continuous copper intake.Accidental administration of excessive amounts of soluble copper salts in mineral mixture, rations, etc.

Animals may ingest copper from sprayed foilage, copper containing pesticides such as Bordeaux mixture.

Copper sulphate used indiscriminately for a longer time or in excessive amount may produce toxicity.

Contamination of forages, pasture or soil in the vicinity of mines and also occur from effluents from industries using copper-like dye.

Soils and plants fertilised with used poultry litter or swine manure also possible sources of poisoning..

Factors affecting Toxicity:Species: All species are susceptible. Sheeps are commonly affected. Horses and swine are relatively tolerant to copper. Dogs are more susceptible to copper overload. Poultry are more resistent to copper poisoning.Interaction: Low levels of dietary Molybdenum and sulphate increases toxicity of copper. Deficiency of Manganese, Iron, B-Vitamins can cause copper to accumulate in the body.

Breeds: Some breeds of dog like Bedlington Terrier breeds are highly sensitive to copper toxicosis.

Stress: Stress from any cause contributes to copper imbalance.

Soil: Sandy soil with low pH possesses the greatest potential leaching copper.

Hepatotoxic Substances precipitate copper toxicosis.

Toxicity:Acute or chronic copper poisoning is encountered in most parts of the world.

Minimum safe and toxic concentration of copper in diet of different species.

Class of AnimalCopper Requirements in Total Diet (ppm)Toxic Level in Total Diet (ppm)Dairy CattleBeef CattleSheepSwinePoultryHorse12-1610 (4-15)7-115-66-894010025>250250-800not known

Toxicokinetics:The absorption of copper from GIT depends on: Chemical form of copper, Interaction with other metals.

Mechanism of ToxicityCopper accumulation in liver may occur from any of these three processes:Abnormal absorption

Abnormal storage

Defective excretion

Mechanism of Toxicity Ruminants: Excessive accumulation of copper occurs in hepatic mitochondria and lysosomes. Affects integrity of plasma membranes. Damages lysosomal membrane, leakage of copper and enzymes into the cytosol, Causes cellular degeneration or necrosis and hepatocyte organelle damage.

Inhibits essential metabolic enzymes. Dihydrolipoyl dehydrogenase inhibition of pyrovate dehydrogenase system disturbance the energy metabolism of cell. 3. Liver damage and necrosis releases large amount from the liver into the blood. Increase fragility of membrane leads erythrocyte lysis, Freeing haemoglobin and causing haemolytic crisis. Excess haemoglobin causes clogging of renal tubules leading to renal tubular and glomerular necrosis and production of darkened (gunmetal) kidneys and death.

Swine: copper inhibits absorption of iron from GIT leading to iron deficiency anaemia.

Dogs: Autosomal recessive defect causes increased copper retention in liver hepatic damage. abnormal binding of copper with hepatic metallothionein sequesters copper in hepatic lysosomes prevents normal biliary excretion of copper.

Clinical Signs:Acute Toxicity: Severe gastroenteritis, salivation, reduced feed consumption, colic, diarrhoea, melena, shock, collapse and death. Haemolysis and haemoglobinuria, jaundice and necrosis of liver.

Chronic Toxicity: Anaemia, depression, weakness and trembling, anorexia, thirst, haemoglobinuria, jaundice, dyspnoea, shock, cold extremities, tachycardia and death. In laying hens decreased egg production, diarrhoea and oral mucosal ulcers and vesicles seen.

Post-mortem Findings:Acute copper poisoning : Gastroenteritis with erosions and ulcerations in abomasum.Chronic poisoning : Jaundice ,methaemoglobin. The lesions include pale yellow liver, enlarged pulpy spleen, distended gall bladder with greenish bile and bluish-black kidneys (known as gunmetal kidneys).Microscopic Lesions: Hepatocyte vaculation, periportal fibrosis, renal tubular necrosis and haemoglobin casts in renal tubules and excessive fragmented erythrocytes in spleen.

Diagnosis: History, Clinical signs and lesions , Copper level in the body fluids, faeces and tissues. Acute copper poisoning, there is evidence of blue-green ingesta, elevated faecal (8,000-10,000 ppm) and kidneys (>15 ppm) copper levels. Chronic poisoning, blood and liver copper concentration are elevated during the haemolytic period Changes in laboratory parameters include elevated bilirubin levels, haemoglobinaemia and haemoglobinuria, elevated levels of AST, LDH, SDH and arginase.Differential Diagnosis: Gastroenteritis and leptospirosis as well as Arsenic, Mercury toxicosis and phenothiazine.

Treatment and Management:Specific Therapy:Chelating agents: Penicillamine bind with copper in blood or tissue and promote its removal through the kidney.D-pencillamine:Sheep: 50 mg/kg orally for six days.Dogs: 10-15 mg/kg twice daily by oral route.

Ascorbic Acid: Given with metals has been found to decrease intestinal absorption of copper in dogs. Dogs:500-1000 mg/dayOral dose of ammonium molybdate (0.5-1 mg/kg/day) and sodium sulphate (6-20 mg/kg/day) may be given to combat chronic copper poisoning.Ammonium tetrathiomolybdate (1.7-3.4 mg/day) three treatments on alternate days by I.V. or S.C.Oral Zinc supplementation decreases intestinal absorption of copper. Dogs: 5-10 mg/kg, orally twice daily.

Supportive Therapy:Complications from hepatic encephalopathy and ascites should be treated as they occur.Anti-oxidant therapy with Vitamin E (400-500 mg/kg, orally) has protective affect against hepatic damage in dogs.Symptomatic Therapy should be carried out to alleviate shock and colic pains.Alkalisation of urine helps to decrease renal damage from haemoglobin.

Prevention:Feed samples should be analysed routinely to monitor the copper : molybdenum ratio in the diet.Supplemental feeds which are known to be low in copper should be used whenever possible.Feeding a properly fortified trace mineralised salt is essential to the health and production of the flock.Steps should be taken to remove the hepatotoxic plants from the pasture and forage..

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