Infectious canine hepatitis - histopeople.upei.ca/lopez/Liver_lecture_4_Final_2009_ppt.pdf ·...
Transcript of Infectious canine hepatitis - histopeople.upei.ca/lopez/Liver_lecture_4_Final_2009_ppt.pdf ·...
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Infectious canine hepatitis - histo
Periacinar hepaticPeriacinar hepatic necrosis (individual hepatocytes)p y )Large intranuclear inclusion bodies (INIB)( )Endothelial damage & hemorrhages in other gorgansMinimal inflammation
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Herpesvirus infection
Lesions• Multifocal hepatic necrosis
in young animals & fetuses • INIBINIB• Minimal inflammation
Agents• Equine herpesvirus 1 -EVR • Bovine herpesvirus 1 -BR• Canine herpesvirus 1
Multifocal hepatic necrosis, IBR, bovine fetus
p• Pseudorabies
Intranuclear inclusion body, equine fetus, EVR
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Other virusesOther viruses
Rift valley feverRift valley feverWesselsbron diseaseI f ti f li it itiInfectious feline peritonitisEquine infectious anemiaAdenoviruses of ruminantsPorcine circovirus 2 (PMWS)Porcine circovirus 2 (PMWS)
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Bacterial infections of the liver
M ltif l ti i h titi
Morphological patterns (Lesions)
Multifocal necrotizing hepatitis AbscessesGranulomasMostly associated with Mycobacteriosis (Tuberculosis)
Epithelioid macrophages laden withEpithelioid macrophages laden with Mycobacterium avium around a blood vessel, dog
Hepatic granulomas, bovine tuberculosis
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Bacterial infections of the liver
Multifocal necrotizing hepatitisMultifocal necrotizing hepatitis • Fetuses and neonates • Salmonella sp• Listeria monocytogenes• Campylobacter spp• Actinobacillus sp
Listeriosis horse Salmonellosis cowListeriosis, horse Salmonellosis, cow(paratyphoid nodules)
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Liver abscessesCommon complication of chemical rumenitis or traumatic reticulitisSingle or multipleMixed bacterial floraMixed bacterial flora
• Fusobacterium necrophorum• Corynebacterium
pseudotuberculosisA h b t i• Archanobacterium pyogenes
• Streptococci and Staphylococci
• Rhodococcus equi
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Liver abscesses
Outcome• Incidental finding at abattoir or• Incidental finding at abattoir or
necropsy• Heal, become encapsulated and
sterile• Cause focal adhesive peritonitis• Break into hepatic vein or vena
cava thrombophlebitis, endocarditis pulmonaryendocarditis, pulmonary aneurisms (rupture with profuse bleeding) or abscesses (rupture with endotoxic shock)
• Generalized infection in young• Generalized infection in young animals
• Toxemia Liver abscess with ruptureinto the caudal vena cava cowinto the caudal vena cava, cow
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Bacillary hemoglobinuriaEtiology: Clostridium hemolyticum • Following liver injury -Following liver injury
migrating liver flukes• Anaerobic environment• Toxins produced by bacteria
d h t ll lproduce hepatocellular necrosis and intravascular hemolysis hemoglobinuria
Species affected: p• Cattle and Sheep
Lesion• Single large area of necrosisg g• Rapid autolysis
Single large area of necrosis due to C. hemolyticum (top).Fascioloides magna migration tracts with black excretory
pigment, cow (bottom)
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Tyzzer's disease
Etio: Clostridium piliformeFormerly Bacillus piliformisFormerly - Bacillus piliformis
Species: • Rodents, • Immunocompromised or• Immunocompromised or
young animals (Foals, calves, kittens, puppies)
Lesions• Multifocal necrotic hepatitis• Colitis
Diagnosis• Bundles of large, long bacilli in
hepatocytes• Silver stain (Warthin-Starry)
Tyzzer’s disease: filamentous bacteria in hepatocytes(Giemsa), also demonstrated with silver stain (right)
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Other bacterial and mycotic diseasesdiseases
Black disease of sheep (Infectious necrotic Dissociation of hepatic
d l t i i d(hepatitis)Etiology: Clostridium novyi
cords, leptospirosis, dog
Leptospirosis
M ti i f tiHemorrhagic infarcts, cow
Mycotic infections• Hemorrhagic infarcts• Granulomatous hepatitis• Granulomatous hepatitis
Blastomyces spp & Histoplasma spp
Yeasts of HistoplasmaYeasts of Histoplasmain the cytoplasm of Kupffer cells and
macrophages
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Parasitic diseases of liverParasitic diseases of liver
NematodesNematodesCestodesT t dTrematodesProtozoa
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NematodesNematodesAscaris suum• “Milk spots" in pig livers• Multiple areas of fibrosis following migration of larvae • Tunnel forms first hemorrhage eosinophilic infiltration and
coagulative necrosis fibrosiscoagulative necrosis fibrosisStrongylus vulgaris - horses• Migration of larvae• Associated with perihepatitis filamentosa??• Associated with perihepatitis filamentosa??
Capillaria hepatica dogs, rodents (adults and eggs in liver)Stephanurus dentatus pigsStephanurus dentatus- pigsDirofilaria immitis (heartworm)• Fatal vena caval syndrome in heavy infections
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Milk spots in a pig liver Adult forms of Ascaris suum in bile ducts, pig
Dirofilariasis, vena caval syndrome, dog. Large collections of adult Dirofilaria immitis are present in the
caudal vena cava. Larval migration, Strongylus vulgaris, horse
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CestodesEcchinonoccus granulosusEcchinonoccus granulosus (Hydatidosis)• Cysts in multiple species
Ad lt i i H d tid i i• Adults are in carnivores• Not that common in
Canada
Hydatidosis, pig
Stilesia hepaticaThysanosoma actinoidesCysticercus tenuicollis.y
Hydatidosis, pigThysanosoma,
sheep
C. tenuicollis, pig
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TrematodesSpecies
• Fasciola hepatica, F. gigantica, Fascioloides magna and Dicrocoelium spp. - ruminants
• Opisthorchis spp. and Platynosomun spp. - dogs and cats
Life cycle• Requires a snail in which larvae• Requires a snail in which larvae
develop into cercaria• Cercaria leave the snail, encyst
and become metacercaria• Infective to the definitive host
Most significant• Fasciola hepatica & F. gigantica -
bile ducts • Fascioloides magna - cysts within
li hliver parenchyma
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Liver flukesLESIONS:• Immature flukes: traumatic
lesions during migration (predispose to bacterial(predispose to bacterial infections in the liver)
• Adults: mechanical and chemical irritation and physical obstruction
chronic cholangitis or cholangiohepatitispipestem liverBlack pigment with FBlack pigment with F. magna
Blood loss
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ProtozoaC ( )Coccidiosis (rabbits)LeishmaniasisToxoplasmosisNeopsporosisHistomoniasis in turkeys Proliferative cholangitis, gross (top)
and histo (bottom), Eimeria stiedae, rabbit
Histomoniasis, turkey
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Toxic liver injuryToxic liver injury
Common siteCommon site • any toxic substance ingested and absorbed
through the GIT goes directly to the liverthrough the GIT goes directly to the liver• liver role is biotransformation of various
endogenous and exogenous substances forendogenous and exogenous substances for excretion.
• Product of bioactivation may be more toxicyMost agents are predictable, a few are idiosyncraticidiosyncratic
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Classification of hepatotoxic liver i jinjury
BiotransformationBiotransformationStimulation of autoimmunitySti l ti f t iStimulation of apoptosisDisruption of calcium homeostasisCanalicular injuryMitochondrial injuryMitochondrial injury
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BiotransformationBiotransformation
Involves cytochrome p450 systemInvolves cytochrome p450 systemLesions most severe in centrilobular areasareasThree steps• Phase I: Bioactivation to high-energy reactivePhase I: Bioactivation to high energy reactive
intermediates• Phase II: Conjugation to water soluble j g
metabolites• Phase III: Excretion into canaliculi
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Hepatotoxic agentsHepatotoxic agents
NumerousNumerous(See Tables 8.1 and 8.2 of Gavin & Zachary,
2007)2007)• Phytotoxins• Mycotoxins• Mycotoxins• Chemicals• Some therapeutic agents• Some therapeutic agents
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Blue-green algaeBlue green algaeMicroscopic protists related to b i (Mi ti A b )bacteria (Microcystis, Anabaena) Grows as bloom on lakes and pondsBl ll i l tBlooms usually occur in late summer or early fallMicrocystin is main preformed toxintoxinLesions• Acute hemorrhagic gastro-
enteritis• Acute centrilobular to massive
hepatic necrosis• Chronic liver disease in survivors
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Pyrrolizidine alkaloid poisoningPyrrolizidine alkaloid poisoning
Common genera are Senecio, Crotalaria g ,Amsinki, Tichodesma and HeliotropiumOccur worldwide and disease is due to a variety
f lk l id hi h d i liof alkaloids which are converted to toxic pyrrolic esters by hepatic cytochrome p450 system. Pigs cattle horses goats and sheep affectedPigs, cattle, horses, goats and sheep affectedLesions• Acute - periacinar necrosisAcute periacinar necrosis• Hepatic veno-occlusive disease• Chronic- more common
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Pyrrolizidine alkaloid poisoning – bovine liver
Finely nodular liver (minimal parenchymal regeneration) Periportal fibrosis and bile duct hyperplasia
Giant hypertrophy of hepatocytes (Megalocytosis) Megalocytes
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Cycads
Contain nontoxicContain nontoxic cycasin• Deconjugated by
intestinal bacteria• Bioactivated in liver
Lesions• similar to those of
pyrrolizidine alkaloidpyrrolizidine alkaloid poisoning in cattle, sheep and goats
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Alsike cloverAlsike clover
Trifolium hybridum found yin North AmericaHorses - chronic liver didiseaseHisto• Fibrosis, bile ductFibrosis, bile duct
hyperplasia, portal hepatitis• Photodynamic dermatitis• NO megalocytosis• NO megalocytosis
Toxic principle unknown
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MycotoxinsMycotoxins
Secondary metabolites of fungiSecondary metabolites of fungiAflatoxinsSporidesminSporidesminPhomopsinPoisonous mushroomsPoisonous mushrooms
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AflatoxinsAflatoxins4 major aflatoxins - B1, B2 G1 & G2B2, G1 & G2. B1 is the most common and potent (carcinogen)Ingested in mouldy feed (corn, peanuts, cottonseed)
Converted to toxic intermediates in hepatocytes Occurrence• Warm humid temperatures • Not a major problem in
Canada
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AflatoxinsAflatoxinsMost common in pigs, poultry, cattle and dog
Acute intoxication (rare except in dogs & ducklings)• Periacinar to massive hepatic lipidosis and necrosis
H h i di h i• Hemorrhagic diathesis• Ducklings - periportal necrosis
Chronic intoxication - more commonS f tt d ti• Severe fatty degeneration
• Fibrosis• Biliary hyperplasia• Megalocytosis• Megalocytosis
Aflatoxins are carcinogenic• Hepatomas• Cholangiocellular tumours• Cholangiocellular tumours
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Sporidesminp
Pithomyces chartarumFound on dead rye grass in warm climates (New Zealand & Australia) Liver pathology due to excretion of unconjugated sporidesmin in bile (Toxic to bile duct epithelium)
L iLesions• Acute to chronic cholangiohepatitis• Photosensitization in sheep
(due to retention of phylloerythrin)
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Sporidesmin toxicity (facial eczema) in sheep
Chronic cholangiohepatitis and bile lakes in sheep with sporidesmin toxicity Bile lakes due to cholestasis