Infectious canine hepatitis - histo

Transcription

1 Infectious canine hepatitis - histo Periacinar hepatic necrosis (individual hepatocytes) Large intranuclear inclusion bodies (INIB) Endothelial damage & hemorrhages in other organs Minimal inflammation

2 Herpesvirus infection Lesions Multifocal hepatic necrosis in young animals & fetuses INIB Minimal inflammation Agents Equine herpesvirus 1 -EVR Bovine herpesvirus 1 -BR Canine herpesvirus 1 Pseudorabies Multifocal hepatic necrosis, IBR, bovine fetus Intranuclear inclusion body, equine fetus, EVR

3 Other viruses Rift valley fever Wesselsbron disease Infectious feline peritonitis iti Equine infectious anemia Adenoviruses of ruminants Porcine circovirus 2 (PMWS)

4 Bacterial infections of the liver Morphological patterns (Lesions) Multifocal l necrotizing i hepatitis Abscesses Granulomas Mostly associated with Mycobacteriosis (Tuberculosis) Epithelioid macrophages laden with Mycobacterium avium around a blood vessel, dog Hepatic granulomas, bovine tuberculosis

5 Bacterial infections of the liver Multifocal necrotizing hepatitis Fetuses and neonates Salmonella sp Listeria monocytogenes Campylobacter spp Actinobacillus sp Listeriosis, horse Salmonellosis, cow (paratyphoid nodules)

6 Common complication of chemical rumenitis or traumatic reticulitis Single or multiple Mixed bacterial flora Fusobacterium necrophorum Corynebacterium pseudotuberculosis Archanobacterium pyogenes Streptococci and Staphylococci Rhodococcus equi Liver abscesses

7 Liver abscesses Outcome Incidental finding at abattoir or necropsy Heal, become encapsulated and sterile Cause focal adhesive peritonitis Break into hepatic vein or vena cava thrombophlebitis, endocarditis, pulmonary aneurisms (rupture with profuse bleeding) or abscesses (rupture with endotoxic shock) Generalized infection in young animals Toxemia Liver abscess with rupture into the caudal vena cava, cow

8 Bacillary hemoglobinuria Etiology: Clostridium hemolyticum Following liver injury - migrating liver flukes Anaerobic environment Toxins produced by bacteria produce hepatocellular l necrosis and intravascular hemolysis hemoglobinuria Species affected: Cattle and Sheep Lesion Single large area of necrosis Rapid autolysis Single large area of necrosis due to C. hemolyticum (top). Fascioloides magna migration tracts with black excretory pigment, cow (bottom)

9 Tyzzer's disease Etio: Clostridium piliforme Formerly - Bacillus piliformis Species: Rodents, 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)

10 Other bacterial and mycotic Black disease of sheep (Infectious necrotic hepatitis) Etiology: Clostridium novyi Leptospirosis diseases Dissociation of hepatic cords, leptospirosis, i dog Mycotic infections Hemorrhagic infarcts Granulomatous hepatitis Blastomyces spp & Histoplasma spp Hemorrhagic infarcts, cow Yeasts of Histoplasma Yeasts of Histoplasma in the cytoplasm of Kupffer cells and macrophages

11 Parasitic diseases of liver Nematodes Cestodes Trematodes Protozoa

12 Nematodes Ascaris suum Milk spots" in pig livers Multiple areas of fibrosis following migration of larvae Tunnel forms first hemorrhage eosinophilic infiltration and coagulative necrosis fibrosis Strongylus vulgaris - horses Migration of larvae Associated with perihepatitis filamentosa?? Capillaria hepatica dogs, rodents (adults and eggs in liver) Stephanurus dentatus- pigs Dirofilaria immitis (heartworm) Fatal vena caval syndrome in heavy infections

13 Milk spots in a pig liver Adult forms of Ascaris suum in bile ducts, pig Larval migration, Strongylus vulgaris, horse Dirofilariasis, vena caval syndrome, dog. Large collections of adult Dirofilaria immitis are present in the caudal vena cava.

14 Cestodes Ecchinonoccus granulosus (Hydatidosis) Cysts in multiple species Adults are in carnivores H d tid i i Not that common in Canada Stilesia hepatica Thysanosoma actinoides Cysticercus tenuicollis. Hydatidosis, pig Thysanosoma, sheep Hydatidosis, pig C. tenuicollis, pig

15 Trematodes Species 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 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 liver parenchyma

16 Liver flukes LESIONS: Immature flukes: traumatic lesions during migration (predispose to bacterial infections in the liver) Adults: mechanical and chemical irritation and physical obstruction chronic cholangitis or cholangiohepatitis pipestem liver Black pigment with F. magna Blood loss

17 Protozoa Coccidiosis (rabbits) Leishmaniasis Toxoplasmosis Neopsporosis Histomoniasis in turkeys Proliferative cholangitis, gross (top) and histo (bottom), Eimeria stiedae, rabbit Histomoniasis, turkey

18 Toxic liver injury Common site any toxic substance ingested and absorbed through the GIT goes directly to the liver liver role is biotransformation of various endogenous and exogenous substances for excretion. Product of bioactivation may be more toxic Most agents are predictable, a few are idiosyncratic

19 Classification of hepatotoxic liver Biotransformation injury Stimulation of autoimmunity Stimulation of apoptosis Disruption of calcium homeostasis Canalicular injury Mitochondrial injury

20 Biotransformation Involves cytochrome p450 system Lesions most severe in centrilobular areas Three steps Phase I: Bioactivation to high-energy reactive intermediates Phase II: Conjugation to water soluble metabolites Phase III: Excretion into canaliculi

21 Hepatotoxic agents Numerous (See Tables 8.1 and 8.2 of Gavin & Zachary, 2007) Phytotoxins Mycotoxins Chemicals Some therapeutic agents

22 Blue-green algae Microscopic protists related to bacteria (Microcystis, Anabaena) ) Grows as bloom on lakes and ponds Blooms usually occur in late summer or early fall Microcystin is main preformed toxin Lesions Acute hemorrhagic gastroenteritis Acute centrilobular to massive hepatic necrosis Chronic liver disease in survivors

23 Pyrrolizidine alkaloid poisoning Common genera are Senecio, Crotalaria Amsinki, Tichodesma and Heliotropium Occur worldwide and disease is due to a variety of alkaloids l which h are converted to toxic pyrrolic esters by hepatic cytochrome p450 system. Pigs, cattle, horses, goats and sheep affected Lesions Acute - periacinar necrosis Hepatic veno-occlusive disease Chronic- more common

24 Pyrrolizidine alkaloid poisoning bovine liver Finely nodular liver (minimal parenchymal regeneration) Periportal fibrosis and bile duct hyperplasia Giant hypertrophy of hepatocytes (Megalocytosis) Megalocytes

25 Cycads Contain nontoxic cycasin Deconjugated by intestinal bacteria Bioactivated in liver Lesions similar to those of pyrrolizidine alkaloid poisoning in cattle, sheep and goats

26 Alsike clover Trifolium hybridum found in North America Horses - chronic liver disease Histo Fibrosis, bile duct hyperplasia, portal hepatitis Photodynamic dermatitis NO megalocytosis Toxic principle unknown

27 Mycotoxins Secondary metabolites of fungi Aflatoxins Sporidesmin Phomopsin Poisonous mushrooms

28 Aflatoxins 4 major aflatoxins - B1, B2, 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

29 Aflatoxins Most common in pigs, poultry, cattle and dog Acute intoxication (rare except in dogs & ducklings) Periacinar to massive hepatic lipidosis and necrosis Hemorrhagic diathesis i Ducklings - periportal necrosis Chronic intoxication - more common Severe fatty degeneration Fibrosis Biliary hyperplasia Megalocytosis Aflatoxins are carcinogenic Hepatomas Cholangiocellular tumours

30 Sporidesmin Pithomyces chartarum Found 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) Lesions Acute to chronic cholangiohepatitis Photosensitization in sheep (due to retention of phylloerythrin)

31 Sporidesmin toxicity (facial eczema) in sheep Chronic cholangiohepatitis and bile lakes in sheep with sporidesmin toxicity Bile lakes due to cholestasis