Flashcards
Liver Toxins
Cards in this deck (34)
- 1AmatoxinsMacrocyclic peptide from Amanita mushroom spp. Dogs most frequently affected, but all species are susceptible.
The bicyclic octapeptides inhibit nuclear RNA pol II which prevents normal transcription and protein synthesis resulting in cell necrosis. - 2CSx, gross and histo path of Amatoxin poisoningFulminant/rapid liver failure, gastroenteritis, hypoglycaemia.
Grossly: massive hepatocellular necrosis, haemorrhages.
Histopath: surviving hepatocytes have vesicular nuclei with chromatic condensation and disintegration of nucleoli - 3—Amanita phalloides (death cap)
- 4Where does Amanita phalloides normally grow?In association with European trees e.g. oaks
- 5Sawfly larval peptidesLophyrotomin
Pergidin
Zootoxins from Australian cattle-poisoning sawfly (Lophyrotoma interrupta). - 6When does sawfly larvae poisoning occur?When cattle ingest larval masses (spp Lophyrotoma interruptus, and L zonalis) at tree bases (usually Eucalyptus melanophloia).
- 7Toxins that cause acute liver necrosisMicrocystins, nodularin (blue-green algae)
Methylazoxymethanol (cycads)
Diterpenoid glycosides (sunflower daisy)
Trematoxin
Furanosesquiterpenes
Macrofungal peptides (Amatoxin)
Sawfly larvae peptides
Aflatoxins (aspergillus flavus) - 8Toxins that cause subacute liver necrosisCylindrospermopsin (from blue green algae)
Aflatoxins - 9AflatoxinsProduced by fungi growing in carb rich substrates (Peanuts, cotton seed, grains).
Includes fungal spp
- Aspergillus flavus
-A parasiticus
-A nomius - 10Species susceptibilityPoultry more than mammals.
Ducklings > turkey poult > chicken.
Dogs> piglet > pregnant sow > calf > cow > sheep - 11Pathogenesis of aflatoxinsAflatoxin metabolised by CYPs and the metabolite binds adenine in nucleic acids which inhibits cell division and hepatocellular regeneration.
Has a carcinogenic effect (as DNA binding causes mutations) and suppresses messenger-RNA synthesis leading to necrosis. - 12Aflatoxin pathologic lesionsLiver: centrilobular necrosis, marked fatty change.
- 13Conditions of aflatoxin poisoning1. Pre-harvest: aflatoxin production in peanuts is promoted by drought and soil temps 26-32C. Insect infestation of peanut pods and cotton seed heads promotes Aspergillus flavus infection.
2. Post-harvest storage: optimal conditions for Aspergillus flavus growth are humid. More likely if water damaged during storage.
The distribution of aflatoxins in feed is not uniform. - 14CSx of aflatoxicosisDepends on the dose. Large doses result in sudden death, low persistent doses resulting in chronic liver failure (jaundice, weight loss or gain).
- 15Post mortum lesions assoc with aflatoxins1. Acute: generalised haemorrhage, severe liver necrosis
2. Subacute: liver necrosis, haemorrhagic gastroenteritis
3. Chronic: fibrosis with megalocytosis, fatty change, biliary retention, biliary ductular hyperplasia, fibrosis. - 16CylindrospermopsinFrom cyanobacteria (algae). A hepatotoxic and nephrotoxic alkaloid.
- 17Sources of cylindrospermopsin1. Cylindrospermopsis raciborskii: most important one, distributed throughout water column (not forming the surface scum).
- 18—Cylindrospermopsis raciborskii
- 19CSx of CylindrospermopsinCattle: weakness progressing to recumbency and death.
Longer clinical course of 3 days. - 20Pathogenesis of cylindrospermopsinPotent inhibitor of mammalian protein synthesis. Targets liver, kidney, heart to cause degeneration and necrosis.
- 21Cylindrospermopsin PM signsGross changes: pale liver, distended gall bladder, +/- jaundice
Histopath changes in liver, kidney, heart - 22Pyrrolizisine alkaloidsMonoesters, non-cyclic diesters and cyclic diesters.
Main target organ is the liver, but also affects the lungs and kidney too. - 23Pathogenesis of pyrrolizidine alkaloidsBioactivation of cytochrome p450 so toxin is converted into toxic pyrrolic metabolites which are electrophilic and form covalent bonds with cell molecules.
Electrophilic metabolites are antimitotic, cause necrosis, and resulting cell loss and inability to replace cells then causing marked fibrosis --> effacement of central veins by collagen --> veno-occlusive disease. - 243 types of pyrrolizidine alkaloid clinical presentation1. Acute exposure of large dose: periacinar zonal necrosis
2. Phasic/seasonal exposure: hepatic atrophy with regenerative nodules with megalocytosis, bile duct hyperplasia.
3. Chronic exposure: fibrotic atrophic livers without nodular regeneration. - 25Factors predisposing to pyrrolizidine alkalosisThey are bitter and unpalatable, so it generally occurs if there is insufficient pasture, hay or bedding is contaminated with PA containing plants, if the silage is contaminated with PA containing plants, or the feed grains is contaminated with PA containing seeds.
- 26Time course of PA toxicosis CSx to developDelayed onset: syndrome onset weeks to months (up to 18 months in cattle) after ingestion. Toxin accumulations in tissues. Sheep and goats are the most resistant as their rumen contains flora able to degrade PA and can more efficiently detoxify PAs in the liver.
- 27Clinical signs of PA toxicosis in orsesHepatotoxcity commoly results in hepatoencephalopathy (walkabout disease). Can be more aggressive than normal.
Compulsive walking or galloping (with skin abrasions on the chest, forelimbs, neck and face), weight loss, slight jaundice, lethargy, muscle tremor, irritability, blindness, head pressing. - 28PA CSx in cattleweight loss, persistent diarrhoea with tenesmus, anorexia, +/- jaundice.
Less commonly may see rectal prolapse, photosensitisation, nervous derangement, haemolysis. - 29PA CSx in sheepWeight loss, jaundice, haemolysis, photosensitisation, ascites
- 30PhomopsinsA mycotoxin, from a fungus that grows on lupin stubble. Cause of subacute or chronic hepatotoxicity with photosensitization, icterus, anorexia.
Grossly: cell degeneration, fatty change, necrosis, atrophic liver, nodular regeneration if discontinuous exposure.
Histo: abnormal mitotic figures, mitotic arrest, bile duct proliferation, pigment accumulation. - 31Pathogenesis of PhomopsinsPhomopsins bind to tubulin and prevent formation of microtubules, causing cytoplasmic microtubular dysfunction in hepatocytes, with marked subcellular/biochemical disruption resulting in accelerated cell death, arrested mitosis and fatty infiltration.
- 32Conditions of phomopsins poisoningGrazing of infected dry lupin stubble in summer/autumn. Contaminated lupin seed may also cause poisoning.
- 33Clinical signs of phomopsinsIn sheep: lethargy, weight loss, jaundice, anaemia, photosensitisation is rare.
Swollen pale liver or a fibrotic liver. - 34Histo path of liver in Lupinosis/phomopsins-necrosis of individual hepatocytes
-many arrested mitotic figures in hepatocytes
-fatty change
-biliary ductular hyperplasia
-fibrosis
-megalocytosis
-lipofuscin in macrophages
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- Veterinary Medicine Flashcards on Liver Toxins , created by Alice Kermond on 24/09/2016.
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- Alice Kermond
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