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− | ==Hepatotoxicity==
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− | *sheep are very susceptible
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− | **they have poor ability to excrete copper in the bile
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− | *copper accumulates in hepatocytes until it reaches a critical level
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− | **the hepatocytes die and release the copper into the blood
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− | **causes haemolysis of the red blood cells
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− | *this haemolysis further damages the hepatocytes
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− | **releases even more copper
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− | ====Predisposing factors====
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− | *contamination of foodstuffs and pasture with copper
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− | *any damage to the biliary system as in ragwort poisoning
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− | *pastures low in molybdenum
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− | **increases the availability of dietary copper
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− | **molybdenum combines with copper to form insoluble complexes in the gut
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− | ====Gross====
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− | *carcass
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− | **jaundiced
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− | **reddish
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− | *[[Liver - Anatomy & Physiology|liver]]
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− | **swollen
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− | **soft
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− | **orange in colour
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− | *[[Urinary System - Anatomy & Physiology#Upper Urinary Tract|kidneys]]
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− | **deep red
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− | **red urine due to haemoglobinuria
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− | ====Microscopically====
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− | *periacinar hepatic necrosis and profuse bile due to haemolysis and cholestasis
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− | *copper can be demonstrated with special stain - rhodanine
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− | ====Genetic inheritance====
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− | *Bedlington and West Highland White Terriers
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− | *copper toxicosis susceptibility
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− | *inherited as autosomal defect
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− | *copper levels can be very high in the [[Liver - Anatomy & Physiology|livers]] of these animals
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− | *there is no haemolytic crisis
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− | =====Clinical=====
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− | *ill thrift
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− | *progressive neurological signs due to [[Liver - Anatomy & Physiology|liver]] failure
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− | =====Gross=====
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− | *[[Liver - Anatomy & Physiology|liver]] is small and fibrosed
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− | *jaundice is not a consistent feature
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− | == Copper and liver disease ==
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| *Copper – cofactor for enzymes (lysyl oxidase), electron transport proteins (cytochrome c oxidase) and antioxidant molecules (superoxide dismutase). | | *Copper – cofactor for enzymes (lysyl oxidase), electron transport proteins (cytochrome c oxidase) and antioxidant molecules (superoxide dismutase). |
− | *Primarily absorbed through the [[Small Intestine - Anatomy & Physiology|small intestine]] and [[Monogastric Stomach - Anatomy & Physiology|stomach]] (upper small intestine in the dog). | + | *Primarily absorbed through the [[Small Intestine Overview - Anatomy & Physiology|small intestine]] and [[Monogastric Stomach - Anatomy & Physiology|stomach]] (upper small intestine in the dog). |
| *Enterocyte regulation of absorption – metallothionein and a copper transport protein – ATPase7A. | | *Enterocyte regulation of absorption – metallothionein and a copper transport protein – ATPase7A. |
| *Metallothionein is a low molecular wt cytoplasmic protein, in all tissues; expression in response to heavy metals, various hormones and stress. metallothionein in cytoplasm of enterocytes leads to absorption of copper. | | *Metallothionein is a low molecular wt cytoplasmic protein, in all tissues; expression in response to heavy metals, various hormones and stress. metallothionein in cytoplasm of enterocytes leads to absorption of copper. |
| *ATPase7A – transmembrane copper transporter in a number of cell types. | | *ATPase7A – transmembrane copper transporter in a number of cell types. |
− | *Defective in people with Menke’s disease – the animal model is the mottled mouse – results in faulty transport of copper out of the cell –leads to copper accumulation in enterocytes. [[Liver - Anatomy & Physiology|Liver]] and brain that have little of the transporter experience copper deficiency. | + | *Defective in people with Menke’s disease – the animal model is the mottled mouse – results in faulty transport of copper out of the cell –leads to copper accumulation in enterocytes. [[Liver - Anatomy & Physiology|Liver]] and brain that have little of the transporter experience [[Copper Deficiency|copper deficiency]]. |
− | *Chronic diet XS of copper leads to accumulation in the [[Liver - Anatomy & Physiology|liver]] . | + | *[[Copper Toxicity|Chronic diet excess of copper]] leads to accumulation in the [[Liver - Anatomy & Physiology|liver]] . |
| *Serum copper – in 2 pools | | *Serum copper – in 2 pools |
| **Exchangeable pool – loosely bound to carrier molecules; 80% of it bound to transcuperin, the rest bound to albumin. | | **Exchangeable pool – loosely bound to carrier molecules; 80% of it bound to transcuperin, the rest bound to albumin. |
| **Other pool – tightly bound to carrier molecules. | | **Other pool – tightly bound to carrier molecules. |
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− | | + | [[Category:Minerals]] |
− | [[Category:Hepatotoxicity,_Chronic]][[Category:Sheep]] | |
− | [[Category:To_Do_-_Clinical]]
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