Pathology of the Liver and Biliary Tract 3 Metabolic ...people.upei.ca › smartinson ›...
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Pathology of the Liver and Biliary Tract – 3 Metabolic Disorders and Infectious Disease
Shannon Martinson, April 2016 http://people.upei.ca/smartinson/
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Normal anatomy & function
Hepatobiliary Injury and responses
Manifestations of hepatic failure
Developmental anomalies & Miscellaneous lesions
Circulatory disturbances
Metabolic & nutritional disturbances
Infectious diseases of the liver (hepatitis)
Toxin-induced liver diseases
Diseases of uncertain cause
Proliferative lesions of the liver
Diseases of the Gallbladder
OUTLINE
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• An essential trace element bound to: • Metallothionein in hepatocyte lysosomes • Ceruloplasmin in blood
• Biliary excretion critical for Cu homeostasis*
• Too much Cu reactive O2 species → lipid peroxidation/necrosis of hepatocytes Cu release into blood hemolytic crisis
METABOLIC DISTURBANCES
Copper Accumulation
http://www.eurowilson.org/rc/org/eurowilson/htm
Copper toxicosis may be due to:
Dietary excess in ruminants
Molybdenum deficiency
Hepatic (cholestatic) disease
Hereditary disorders
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Hemoglobinuric nephrosis
METABOLIC DISTURBANCES
Copper Accumulation Copper Toxicosis in Sheep
Diagnosis: Submit fresh liver for copper quantification
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METABOLIC DISTURBANCES
Copper Accumulation Hereditary Copper Toxicosis
Rhodanine stain Rubeanic acid stain
• Bedlington terriers • Autosomal recessive
disease impaired biliary excretion of Cu progressive liver disease
• Similar conditions in other dog breeds
• Dalmatian, Skye terrier, WHW terrier, Lab
• Increased hepatic copper may occur secondary to liver disease in any breed
Diagnosis: Submit fresh liver for copper quantification
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Bile
• Cholestasis
Hemosiderin
• Accumulation without liver damage = Hemosiderosis
• Accumulation resulting in liver damage = Hemochromatosis
Parasite hematin
• Fluke puke
METABOLIC DISTURBANCES
Pigments
Hemochromatosis, Rhinoceros
http://vet.uga.edu/ivcvm/courses/afip/conf07/wsc23/wsc23_c01_fig02.jpg
Hemosiderosis, Pig Cholestasis, Dog
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Pathologic Basis of Veterinary Disease (2006), 4th ed., Mosby-Elsevier, chapter 8
METABOLIC DISTURBANCES
Pigments Hematin pigment from Fascioloides magna, liver, ox
Bile
• Cholestasis
Hemosiderin
• Accumulation without liver damage = Hemosiderosis
• Accumulation resulting in liver damage = Hemochromatosis
Parasite hematin
• Fluke puke
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Pathologic Basis of Veterinary Disease (2006), 4th ed., Mosby-Elsevier, chapter 8
Areas of massive necrosis and hemorrhage appear as dark regions of different size scattered throughout the liver
NUTRITIONAL DISEASES OF THE LIVER
Hepatosis dietetica
Centrilobular to massive necrosis and hemorrhage
• Disease of Pigs • Vitamin E/Selenium deficiency • Hemorrhagic centrilobular to massive necrosis
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• Viruses
• Bacteria
• Fungi
• Helminths
• Protozoa
INFECTIOUS DISEASES OF THE LIVER
• Hematogenous • Portal vein - from the GIT • Hepatic artery - sepsis • Umbilical vein – newborns
• Ascending (via bile ducts)
• Direct extension
Portals of entry of organisms
Infectious Agents
Image: Dr C Legge
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INFECTIOUS DISEASES OF THE LIVER – VIRAL INFECTIONS
Infectious Canine Hepatitis (ICH) Etiology: Canine Adenovirus 1
Exposure to urine
Tonsillitis
Viremia
Targets hepatocytes, endothelial cells and urinary epithelial cells
Clinical Signs: • Vomiting • Diarrhea • Petechiae • Hemorrhagic Diathesis • Icterus
Pathogenesis:
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INFECTIOUS DISEASES OF THE LIVER – VIRAL INFECTIONS
Infectious Canine Hepatitis (ICH) Etiology: Canine Adenovirus 1
Gross Lesions: • Enlarged, turgid, friable, congested liver • Paint brush serosal hemorrhages • Widespread petechia • Gall bladder edema* • Hemorrhagic renal infarcts • Blue eye*
www.nmda.nmsu.edu/animal-and-plant-protection/veterinary-diagnostic-services https://instruction.cvhs.okstate.edu/AnatomicPathology/images/dx1-14.JPG
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INFECTIOUS DISEASES OF THE LIVER – VIRAL INFECTIONS
Infectious Canine Hepatitis (ICH) Etiology: Canine Adenovirus 1
Gross Lesions: • Enlarged, turgid, friable, congested liver • Paint brush serosal hemorrhages • Widespread petechia • Gall bladder edema* • Hemorrhagic renal infarcts • Blue eye*
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Eosinophilic intranuclear inclusion bodies (arrows)
Histology: • Centrilobular + single cell necrosis
• Large intranuclear inclusion bodies • Hepatocytes, Endothelial cells, Kupffer cells
• Endothelial damage & hemorrhages
• Minimal inflammation
Single cell necrosis of hepatocytes
INFECTIOUS DISEASES OF THE LIVER – VIRAL INFECTIONS
Infectious Canine Hepatitis (ICH)
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Multifocal hepatic necrosis, IBR, bovine fetus
INFECTIOUS DISEASES OF THE LIVER – VIRAL INFECTIONS
Herpesvirus infections
• Occurs in young animals and fetuses
• Gross lesions
• Small white foci scattered randomly in the liver = multifocal hepatic necrosis
Etiology: • Equine herpesvirus-1 (EVR) • Bovine herpesvirus-1 (IBR) • Canine herpesvirus-1 • Felid herpesvirus-1 (FVR) • Suid herpesvirus-1
(Pseudorabies)
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• Histologic Lesions
• Multifocal necrosis with minimal inflammation
• Intranuclear inclusion bodies In hepatocytes
Intranuclear inclusion body (arrow)
INFECTIOUS DISEASES OF THE LIVER – VIRAL INFECTIONS
Herpesvirus infections
Etiology: • Equine herpesvirus-1 (EVR) • Bovine herpesvirus-1 (IBR) • Canine herpesvirus-1 • Felid herpesvirus-1 (FVR) • Suid herpesvirus-1
(Pseudorabies)
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• Mutated Feline Enteric Coronavirus (Feline Infectious Peritonitis)
• Porcine circovirus 2
• Adenoviruses of ruminants
• Equine infectious anemia
• Rift valley fever
• Wesselsbron disease
INFECTIOUS DISEASES OF THE LIVER – VIRAL INFECTIONS
Other viruses Pyogranulomatous hepatitis, FIP, Cat
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INFECTIOUS DISEASES OF THE LIVER – BACTERIAL INFECTIONS
MORPHOLOGIC PATTERNS
Multifocal necrotizing hepatitis
Abscesses
Granulomas
These lesions can look very similar: • Think about species
appropriate differentials! • When mild – lesions look
similar to viral and protozoal infections
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• Salmonella sp • Listeria monocytogenes • Campylobacter spp • Fusobacterium necrophorum • Actinobacillus sp • Francisella tularensis
Necrobacillosis, Fusobacterium necrophorum, lamb
INFECTIOUS DISEASES OF THE LIVER – BACTERIAL INFECTIONS
Multifocal necrotizing hepatitis
• Most often occurs in fetuses and neonates
Noah’s arkive
Tularemia, Francisella tularensis, beaver
Campylobacter fetus, lamb Listeriosis, Listeria monocytogenes, Chinchilla
www.askjpc.org/wsco/wsc/images/2008/080803-1.jpg
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INFECTIOUS DISEASES OF THE LIVER – BACTERIAL INFECTIONS
Fusobacterium necrophorum, lamb
• Fusobacterium necrophorum • Trueperella pyogenes • Streptococci and Staphylococci • Corynebacterium pseudotuberculosis • Rhodococcus equi
Liver Abscesses • Single or multiple • Often follows chemical rumenitis and TRP in cattle
Trueperella pyogenes, cow
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Pathologic Basis of Veterinary Disease , 5thed., Mosby-Elsevier
INFECTIOUS DISEASES OF THE LIVER – BACTERIAL INFECTIONS
• Single or multiple • Often follows chemical rumenitis and TRP in cattle
Rhodococcus equi, goat
Sheep, Hepatic abscess, Corynebacterium pseudotuberculosis
• Fusobacterium necrophorum • Trueperella pyogenes • Streptococci and Staphylococci • Corynebacterium pseudotuberculosis • Rhodococcus equi
Liver Abscesses
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Significance
• Incidental finding
• Become encapsulated and sterile
• Cause fibrous adhesions
INFECTIOUS DISEASES OF THE LIVER – BACTERIAL INFECTIONS
Sheep, Corynebacterium pseudotuberculosis
Liver Abscesses
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Significance
• Break into hepatic vein or vena cava • Thrombophlebitis • Endocarditis • Pulmonary aneurysms • Lung abscesses
• Generalized infection in young
• Rupture and toxemia
INFECTIOUS DISEASES OF THE LIVER – BACTERIAL INFECTIONS
Liver Abscesses
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Pathologic Basis of Veterinary Disease, 5thed., Mosby-Elsevier
INFECTIOUS DISEASES OF THE LIVER – BACTERIAL INFECTIONS
Hepatic Granulomas
Mycobacterium bovis
Tuberculosis, cattle
Johne’s Disease
Mycobacterium avium paratuberculosis
www.askjpc.org/wsco/wsc/images/2010/101003-3.jpg
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Lesion • Single large area of hepatic
necrosis • Rapid autolysis
• Cattle & sheep – acute and highly fatal
• Pathogenesis:
Noah’s arkive
INFECTIOUS DISEASES OF THE LIVER – BACTERIAL INFECTIONS
Bacillary Hemoglobinuria Etiology: Clostridium hemolyticum
Liver injury by migrating flukes
Anaerobic environment
Germination of Cl hemolyticum spores (latent in
the liver)
Release exotoxins
Liver necrosis and
intravascular hemolysis
Hemoglobinuria
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INFECTIOUS DISEASES OF THE LIVER – BACTERIAL INFECTIONS
Black Disease (Infectious Necrotic Hepatitis) Etiology: Clostridium novyi • Sheep, cattle, pigs, horses
• Pathogenesis:
Noah’s arkive
Lesion • Multifocal hepatic necrosis • Subcutaneous congestion and hemorrhage
Liver injury by migrating flukes
Anaerobic environment
Germination of Cl novyi spores
(latent in the liver)
Release exotoxins
Liver necrosis and Vascular
damage
Subcutaneous hemorrhage
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Affects:
• Rodents
• Immunocompromised or young foals, calves, kittens, puppies
Lesions
• Multifocal necrotizing hepatitis
• Necrotizing colitis
Multifocal necrotizing hepatitis, foal. Cl. piliforme
Pathologic Basis of Veterinary Disease, 5thed., Mosby-Elsevier
INFECTIOUS DISEASES OF THE LIVER – BACTERIAL INFECTIONS
Tyzzer’s Disease Etiology: Clostridium pilliforme
Multifocal necrotizing hepatitis, kitten Cl. piliforme
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Warthin-Starry stain
Pathologic Basis of Veterinary Disease, 5thed., Mosby-Elsevier
INFECTIOUS DISEASES OF THE LIVER – BACTERIAL INFECTIONS
Tyzzer’s Disease Clostridiumpilliforme Etiology: Clostridium pilliforme
Diagnosis: • Difficult to culture * • Histology:
• Bundles of long bacilli in hepatocytes
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Yeasts of Histoplasma in the cytoplasm of Kupffer cells and macrophages Pathologic Basis of Veterinary Disease (2006), 4th ed., Mosby-Elsevier.
INFECTIOUS DISEASES OF THE LIVER – MYCOTIC INFECTIONS
• Hemorrhagic infarcts • Cattle – resulting from mycotic rumenitis
• Granulomatous hepatitis • Blastomyces dermatitidis • Histoplasma capsulatum
Mycotic infections may cause:
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• Adults live in the intestine of pigs • Larvae migrate through the liver • Tunnel hemorrhage eosinophilic
infiltration/coagulative necrosis fibrosis • Multifocal fibrosis = “Milk spots"
INFECTIOUS DISEASES OF THE LIVER – PARASITIC INFECTIONS
Nematodes Ascaris suum
Other nematodes that migrate through liver: • Stephanurus dentatus – pigs • Strongylus vulgaris – horse
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INFECTIOUS DISEASES OF THE LIVER – PARASITIC INFECTIONS
Nematodes
• Fatal vena caval (postcaval) syndrome in heavy infections – DIC, Intravascular hemolysis, acute hepatic failure
Dirofiliaria immitis
Cornell Veterinary Medicine
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Cysticercosis ((Taenia sp), liver, pocupine
Adult tapeworm in GIT
Larval tapeworms (cysticerci) encysted within tissues or on serosal surfaces
Usually incidental
INFECTIOUS DISEASES OF THE LIVER – PARASITIC INFECTIONS
Cestodes
Cysticercosis (T. hydatigena), liver, pig
Taenia spp Cysticerosis
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• Adult tapeworm in canid GIT
• Larval form encysts in viscera – sheep,many species
• Zoonotic – people can get hydatid cysts
INFECTIOUS DISEASES OF THE LIVER – PARASITIC INFECTIONS
Cestodes
http://sydney.edu.au/mbi/images/imagebank/hydatliv.jpg
Echinococcus granulosus
Hydatosis
Cestodes with adult form in biliary tract: • Stilesia hepatica • Thysanosoma actinoides
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Cholangitis, Fasciola hepatica, liver, cow
Fasciola hepatica
INFECTIOUS DISEASES OF THE LIVER – PARASITIC INFECTIONS
Trematodes
• Fasciola hepatica* • Fasciola gigantica • Fascioloides magna* • Dicrocoelium • Opisthorchis • Platynosum
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• Immature flukes: Hemorrhage/necrosis during migration
• +/- activate Clostridial spores
• Adults: mechanical/chemical irritation/physical obstruction
• Fibrosing cholangitis (pipestem liver) - F hepatica • Parenchymal cysts and Pigment - F magna
• Blood loss
Pipestem liver, F hepatica, cow
INFECTIOUS DISEASES OF THE LIVER – PARASITIC INFECTIONS
Trematodes
Cornell Veterinary Medicine Migratory tracts, F hepatica, liver, sheep
Fascioloides magna, liver, caribou
Lesions
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• Histomoniasis in turkeys*
• Coccidiosis (rabbits)*
• Leishmaniasis
• Toxoplasmosis
• Neosporosis
INFECTIOUS DISEASES OF THE LIVER – PARASITIC INFECTIONS
Protozoa
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• Turkeys > Chickens
• Typhlitis
• Target-like areas of Hepatic necrosis
• Transmitted in the ova of Heterakis gallinarum
INFECTIOUS DISEASES OF THE LIVER – PARASITIC INFECTIONS
Protozoa
Histomonas meleagridis
Histomoniasis
“Black head”
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INFECTIOUS DISEASES OF THE LIVER – PARASITIC INFECTIONS
Protozoa
Eimeria stiedae
Hepatic Coccidiosis • Coccidia reside in biliary
epithelial cells - rabbits • Proliferative cholangitis
www.askjpc.org/wsco/wsc/images/2008/080403-1
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