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| | [[Hepatoxicity, Acute]] | | [[Hepatoxicity, Acute]] |
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| − | ==Chronic hepatoxicity==
| + | [[Hepatoxicity, Chronic]] |
| − | Is associated with the continual ingestion of toxic compounds at low doses over a period of time
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| − | There will be evidence of regeneration and repair of the damaged tissue ie fibrosis and biliary hyperplasia
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| − | ===Ragwort===
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| − | *''Senecio jacobaea''
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| − | *plant toxin ingested over a long period of time
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| − | *livestock
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| − | **cattle and horses are more susceptible than sheep
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| − | **livestock will not normally eat the fresh plant
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| − | **most cases arise in horses and cattle consuming ragwort in hay or silage
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| − | *'''pyrrolizidine alkaloids'''
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| − | **toxic principle converted in the body to the toxic intermediate '''pyrroles''' and their esters
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| − | **cause intitial and continued damage to hepatocytes
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| − | **have an anti-mitotic effect whilst allowing continued synthesis within the cell and its nucleus
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| − | ***causes a marked increase in the size of parenchymal cells, a phenomenon termed ''''megalocytosis''''
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| − | ***these very enlarged hepatocytes can be up to 20 times bigger
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| − | ***the enlarged cells are closely apposed so that the sinusoids may not be evident
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| − | *it is likely that the vascular component of the attempted repair of the chronic damage by fibrosis (really a type of granulation tissue) aids the shunting from the portal triads to the central vein and thereby bypassing the hepatocytes
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| − | *other plant and fungal toxins perform in the same way
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| − | ====Gross====
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| − | *slightly enlarged [[Liver - Anatomy & Physiology|liver]]
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| − | *pale in colour
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| − | *very firm to section
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| − | ====Microscopically====
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| − | *necrosis
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| − | *haemorrhage
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| − | *diffuse fibrosis
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| − | ===Mycotoxins===
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| − | *metabolites of fungi
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| − | *'''Alfatoxins''' produced by ''Aspergillus flavus'' and other species
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| − | *main expression
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| − | **chronic intoxication in livestock following fungal growth on badly stored (moisture) grain
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| − | *isolated toxins
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| − | **B1 - the most potent
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| − | **B2
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| − | **G1
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| − | **G2
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| − | *toxic intermediates bind to cellular nuclei acids and proteins
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| − | **potent toxins, carcinogens, and teratogens (the last two are less important in domestic animals)
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| − | *lesions similar to ragwort poisoning, including the hepatocytic cytomegaly
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| − | ===Copper===
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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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