Pathology of the Liver and Biliary Tract 3 Metabolic Disorders and Infectious Disease. Shannon Martinson, 2017

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1 Pathology of the Liver and Biliary Tract 3 Metabolic Disorders and Infectious Disease Shannon Martinson,

OUTLINE Normal anatomy & function Hepatobiliary injury and responses Manifestations of hepatic failure Developmental anomalies and miscellaneous lesions Circulatory disturbances Metabolic &

2 OUTLINE Normal anatomy & function Hepatobiliary injury and responses Manifestations of hepatic failure Developmental anomalies and 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 and bile ducts

Copper Accumulation METABOLIC DISTURBANCES Cu is an essential trace element bound to: Metallothionein in hepatocyte lysosomes Ceruloplasmin in blood Biliary excretion critical for Cu homeostasis* Too

3 Copper Accumulation METABOLIC DISTURBANCES Cu is an essential trace element bound to: Metallothionein in hepatocyte lysosomes Ceruloplasmin in blood Biliary excretion critical for Cu homeostasis* Too much Cu reactive O 2 species lipid peroxidation/necrosis of hepatocytes Cu release into blood hemolytic crisis Copper toxicosis may be due to: Dietary excess in ruminants Molybdenum deficiency Hepatic (cholestatic) disease Hereditary disorders

4 Copper Accumulation METABOLIC DISTURBANCES Hemoglobinuric nephrosis Copper Toxicosis in Sheep Diagnosis: Submit fresh liver for copper quantification

Autosomal recessive disease (COMMD1) impaired

terriers, WHW terriers, Labs Increased hepatic

any breed Special stains for copper Diagnosis:

5 Copper Accumulation METABOLIC DISTURBANCES Hereditary Copper Toxicosis Bedlington terriers Autosomal recessive disease (COMMD1) impaired biliary excretion of Cu progressive liver disease with necrosis cirrhosis Similar conditions in other dog breeds Dalmatians, Skye terriers, WHW terriers, Labs Increased hepatic copper may occur secondary to liver disease in any breed Special stains for copper Diagnosis: Submit fresh liver for copper quantification Rhodanine stain Rubeanic acid stain

Accumulation resulting in liver damage =

6 Pigments METABOLIC DISTURBANCES Cholestasis, Dog Hemosiderosis, Pig Bile Cholestasis Hemosiderin Accumulation without liver damage = Hemosiderosis Accumulation resulting in liver damage = Hemochromatosis Parasite hematin Fluke puke Hemochromatosis, Rhinoceros

Fascioloides magna, liver, ox Bile Cholestasis Hemosiderin Accumulation without

7 Pathologic Basis of Veterinary Disease (2006), 4 th ed., Mosby-Elsevier, chapter 8 Pigments METABOLIC DISTURBANCES 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

Hepatosis dietetica NUTRITIONAL DISEASES OF THE LIVER Disease of Pigs

massive necrosis Centrilobular to massive necrosis and hemorrhage Areas

size scattered throughout the liver May have gallbladder edema

8 Hepatosis dietetica NUTRITIONAL DISEASES OF THE LIVER Disease of Pigs Etiology: Vitamin E/Selenium deficiency Hemorrhagic centrilobular to massive necrosis Centrilobular to massive necrosis and hemorrhage Areas of massive necrosis and hemorrhage appear as dark regions of different size scattered throughout the liver May have gallbladder edema Pathologic Basis of Veterinary Disease (2006), 4 th ed., Mosby-Elsevier, chapter 8

9 INFECTIOUS DISEASES OF THE LIVER Portals of entry of organisms Hematogenous Portal vein: from the GIT Hepatic artery: sepsis Umbilical vein: newborns Ascending (via bile ducts) Direct extension Viruses Bacteria Fungi Helminths Protozoa Image: Dr C Legge

INFECTIOUS DISEASES OF THE LIVER VIRAL INFECTIONS Infectious Canine Hepatitis (ICH) Etiology: Canine Adenovirus 1 Clinical Signs: Vomiting Diarrhea

10 INFECTIOUS DISEASES OF THE LIVER VIRAL INFECTIONS Infectious Canine Hepatitis (ICH) Etiology: Canine Adenovirus 1 Clinical Signs: Vomiting Diarrhea Petechiae Hemorrhagic Diathesis Icterus Pathogenesis: Tonsillitis Viremia Targets hepatocytes, endothelial cells and urinary epithelial cells Exposure to urine

turgid, friable, congested liver Paint brush serosal hemorrhages

11 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*

petechia Gall bladder edema* Hemorrhagic renal infarcts Blue eye*

12 Infectious Canine Hepatitis (ICH) Gross Lesions: Enlarged, turgid, friable, congested liver Paint brush serosal hemorrhages Widespread petechia Gall bladder edema* Hemorrhagic renal infarcts Blue eye* INFECTIOUS DISEASES OF THE LIVER VIRAL INFECTIONS Etiology: Canine Adenovirus 1

Large intranuclear inclusion bodies Hepatocytes, Endothelial cells, Kupffer cells

13 Infectious Canine Hepatitis (ICH) Single cell necrosis of hepatocytes INFECTIOUS DISEASES OF THE LIVER VIRAL INFECTIONS Histology: Centrilobular + single cell necrosis Large intranuclear inclusion bodies Hepatocytes, Endothelial cells, Kupffer cells Endothelial damage & hemorrhages Minimal inflammation Eosinophilic intranuclear inclusion bodies

Herpesvirus infections INFECTIOUS DISEASES OF THE LIVER VIRAL INFECTIONS Multifocal hepatic necrosis, IBR, bovine fetus Etiology: Equine herpesvirus-1 (EVR) Bovine herpesvirus-1 (IBR) Canine

14 Herpesvirus infections INFECTIOUS DISEASES OF THE LIVER VIRAL INFECTIONS Multifocal hepatic necrosis, IBR, bovine fetus Etiology: Equine herpesvirus-1 (EVR) Bovine herpesvirus-1 (IBR) Canine herpesvirus-1 Felid herpesvirus-1 (FVR) Suid herpesvirus-1 (Pseudorabies) Infections in neonatal animals and fetuses Gross lesions Small white foci scattered randomly in the liver = multifocal hepatic necrosis

herpesvirus-1 (FVR) Suid herpesvirus-1 (Pseudorabies) Intranuclear inclusion body

15 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) Intranuclear inclusion body Histologic Lesions Multifocal necrosis with minimal inflammation Intranuclear inclusion bodies In hepatocytes

16 INFECTIOUS DISEASES OF THE LIVER VIRAL INFECTIONS Other viruses Pyogranulomatous hepatitis, FIP, Cat Mutated Feline Enteric Coronavirus (FIP) Porcine circovirus 2 Adenoviruses of ruminants Equine infectious anemia Rift valley fever Wesselsbron disease

17 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

Multifocal necrotizing hepatitis Most often occurs in fetuses and neonates

necrophorum Actinobacillus sp Francisella tularensis INFECTIOUS DISEASES OF THE

askjpc.org/wsco/wsc/images/2008/080803-1.

18 Multifocal necrotizing hepatitis Most often occurs in fetuses and neonates Salmonella sp Listeria monocytogenes Campylobacter spp Fusobacterium necrophorum Actinobacillus sp Francisella tularensis INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Listeriosis, Listeria monocytogenes, Chinchilla Campylobacter fetus, lamb Noah s arkive Necrobacillosis, Fusobacterium necrophorum, lamb Tularemia, Francisella tularensis, beaver

Hepatic Granulomas INFECTIOUS DISEASES OF THE

19 Hepatic Granulomas INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Pathologic Basis of Veterinary Disease, 5 th ed., Mosby-Elsevier Tuberculosis, cattle Mycobacterium bovis Mycobacterium avium paratuberculosis Johne s Disease

Liver Abscesses Single or multiple Often follows

necrophorum Trueperella pyogenes Streptococci and

20 Liver Abscesses Single or multiple Often follows chemical rumenitis and TRP in cattle INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Fusobacterium necrophorum, lamb Fusobacterium necrophorum Trueperella pyogenes Streptococci and Staphylococci Corynebacterium pseudotuberculosis Rhodococcus equi Trueperella pyogenes, cow

Liver Abscesses Single or multiple Often follows chemical rumenitis and TRP in cattle INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Sheep, Hepatic abscess, Corynebacterium pseudotuberculosis

21 Liver Abscesses Single or multiple Often follows chemical rumenitis and TRP in cattle INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Sheep, Hepatic abscess, Corynebacterium pseudotuberculosis Fusobacterium necrophorum Trueperella pyogenes Streptococci and Staphylococci Corynebacterium pseudotuberculosis Rhodococcus equi Rhodococcus equi, goat Pathologic Basis of Veterinary Disease, 5 th ed., Mosby-Elsevier

22 Liver Abscesses Sheep, Corynebacterium pseudotuberculosis INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Significance Incidental finding Become encapsulated and sterile Cause fibrous adhesions

Thrombophlebitis Endocarditis Pulmonary aneurysms Lung

23 Liver Abscesses INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Significance Break into vena cava Thrombophlebitis Endocarditis Pulmonary aneurysms Lung abscesses Generalized infection (sepsis) Cornell Veterinary Medicine

Bacillary Hemoglobinuria Cattle & sheep acute and highly fatal Pathogenesis: INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Etiology: Clostridium haemolyticum Liver injury by migrating flukes

24 Bacillary Hemoglobinuria Cattle & sheep acute and highly fatal Pathogenesis: INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Etiology: Clostridium haemolyticum Liver injury by migrating flukes Anaerobic environment Germination of Cl hemolyticum spores (latent in the liver) Release exotoxins Liver necrosis and intravascular hemolysis Hemoglobinuria Lesion Single large area of hepatic necrosis Rapid autolysis Noah s arkive

environment Germination of Cl novyi spores (latent in the liver) Release exotoxins Liver necrosis and Vascular

25 INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Black Disease (Infectious Necrotic Hepatitis) Etiology: Clostridium novyi Sheep, cattle, pigs, horses Pathogenesis: 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 Lesion Multifocal hepatic necrosis Subcutaneous congestion and hemorrhage Noah s arkive

necrotizing hepatitis Necrotizing colitis Pathologic Basis of Veterinary Disease, 5 th ed.

26 INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Tyzzer s Disease Etiology: Clostridium pilliforme Affects: Rodents Immunocompromised or young foals, calves, kittens, puppies Lesions Multifocal necrotizing hepatitis Necrotizing colitis Pathologic Basis of Veterinary Disease, 5 th ed., Mosby-Elsevier Multifocal necrotizing hepatitis, kitten Cl. piliforme Multifocal necrotizing hepatitis, foal. Cl. piliforme

Diagnosis: Difficult to culture * Histology: Bundles of long

27 Tyzzer s Disease INFECTIOUS DISEASES OF THE LIVER BACTERIAL INFECTIONS Etiology: Clostridiumpilliforme Warthin-Starry stain Diagnosis: Difficult to culture * Histology: Bundles of long bacilli in hepatocytes Pathologic Basis of Veterinary Disease, 5 th ed., Mosby-Elsevier

Blastomyces dermatitidis Histoplasma capsulatum Yeasts of Histoplasma in the cytoplasm of

28 INFECTIOUS DISEASES OF THE LIVER MYCOTIC INFECTIONS Mycotic infections may cause: Hemorrhagic infarcts Cattle resulting from mycotic rumenitis Granulomatous hepatitis Blastomyces dermatitidis Histoplasma capsulatum Yeasts of Histoplasma in the cytoplasm of Kupffer cells and macrophages Pathologic Basis of Veterinary Disease (2006), 4 th ed., Mosby-Elsevier.

Nematodes Ascaris suum INFECTIOUS DISEASES

29 Nematodes Ascaris suum INFECTIOUS DISEASES OF THE LIVER PARASITIC INFECTIONS Adults live in the intestine of pigs Larvae migrate through the liver Tunnel hemorrhage eosinophilic infiltration/coagulative necrosis fibrosis Multifocal fibrosis = Milk spots"

30 Nematodes INFECTIOUS DISEASES OF THE LIVER PARASITIC INFECTIONS Dirofiliaria immitis Fatal vena caval (postcaval) syndrome in heavy infections DIC, Intravascular hemolysis, acute hepatic failure Cornell Veterinary Medicine

31 Cestodes INFECTIOUS DISEASES OF THE LIVER PARASITIC INFECTIONS Echinococcus granulosus Hydatosis Adult tapeworm in canid GIT Larval form encysts in viscera sheep,many species Zoonotic people can get hydatid cysts

32 Cestodes INFECTIOUS DISEASES OF THE LIVER PARASITIC INFECTIONS Taenia spp Cysticerosis Adult tapeworm in GIT Larval tapeworms (cysticerci) encysted within tissues or on serosal surfaces Usually incidental Cysticercosis (T. hydatigena), liver, pig Cysticercosis (Taenia sp), liver, pocupine

33 Trematodes INFECTIOUS DISEASES OF THE LIVER PARASITIC INFECTIONS Cholangitis, Fasciola hepatica, liver, cow Fasciola hepatica* Fasciola gigantica Fascioloides magna* Dicrocoelium Opisthorchis Platynosum Fasciola hepatica

migration May activate Clostridial spores if present

obstruction Fibrosing cholangitis (pipestem liver) - F

Veterinary Medicine Migratory tracts, F hepatica, liver,

34 Trematodes INFECTIOUS DISEASES OF THE LIVER PARASITIC INFECTIONS Immature flukes: Hemorrhage/necrosis during migration May activate Clostridial spores if present Adults: Cause mechanical/chemical irritation/physical obstruction Fibrosing cholangitis (pipestem liver) - F hepatica Parenchymal cysts and pigment - F magna Cornell Veterinary Medicine Migratory tracts, F hepatica, liver, sheep Fascioloides magna, liver, caribou Pipestem liver, F hepatica, cow

35 Protozoa Histomoniasis in turkeys* Coccidiosis (rabbits)* Leishmaniasis Toxoplasmosis Neosporosis Amoebiasis INFECTIOUS DISEASES OF THE LIVER PARASITIC INFECTIONS Entamoeba invadens in a reticulated python

36 Protozoa INFECTIOUS DISEASES OF THE LIVER PARASITIC INFECTIONS Histomoniasis Black head Histomonas meleagridis Turkeys > Chickens Typhlitis Target-like areas of Hepatic necrosis Transmitted in the ova of Heterakis gallinarum

37 INFECTIOUS DISEASES OF THE LIVER PARASITIC INFECTIONS Protozoa Hepatic Coccidiosis Eimeria stiedae Disease of rabbits Coccidia live in biliary epithelial cells Proliferative cholangitis

Pathology of the Liver and Biliary Tract 3 Metabolic Disorders and Infectious Disease

Pathology of the Liver and Biliary Tract 3 Metabolic Disorders and Infectious Disease Shannon Martinson, April 2016 http://people.upei.ca/smartinson/ OUTLINE Normal anatomy & function Hepatobiliary Injury