Infectious canine hepatitis - histo

Periacinar hepaticPeriacinar hepatic necrosis (individual hepatocytes)p y )Large intranuclear inclusion bodies (INIB)( )Endothelial damage & hemorrhages in other gorgansMinimal inflammation

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

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)

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

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)

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

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

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)

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)

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

Parasitic diseases of liverParasitic diseases of liver

NematodesNematodesCestodesT t dTrematodesProtozoa

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

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

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

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

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

ProtozoaC ( )Coccidiosis (rabbits)LeishmaniasisToxoplasmosisNeopsporosisHistomoniasis in turkeys Proliferative cholangitis, gross (top)

and histo (bottom), Eimeria stiedae, rabbit

Histomoniasis, turkey

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

Classification of hepatotoxic liver i jinjury

BiotransformationBiotransformationStimulation of autoimmunitySti l ti f t iStimulation of apoptosisDisruption of calcium homeostasisCanalicular injuryMitochondrial injuryMitochondrial injury

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

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

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

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

Pyrrolizidine alkaloid poisoning – bovine liver

Finely nodular liver (minimal parenchymal regeneration) Periportal fibrosis and bile duct hyperplasia

Giant hypertrophy of hepatocytes (Megalocytosis) Megalocytes

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

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

MycotoxinsMycotoxins

Secondary metabolites of fungiSecondary metabolites of fungiAflatoxinsSporidesminSporidesminPhomopsinPoisonous mushroomsPoisonous mushrooms

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

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

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)

Sporidesmin toxicity (facial eczema) in sheep

Chronic cholangiohepatitis and bile lakes in sheep with sporidesmin toxicity Bile lakes due to cholestasis