Date post: | 07-Apr-2018 |
Category: |
Documents |
Upload: | truongthuy |
View: | 369 times |
Download: | 8 times |
PATHOLOGY OF LIVER & BILIARY TRACT
Enrique Aburto Winter 2015
Lecture 4
Bacterial &
parasitic
infections;
toxin-
induced
liver
diseases
7.2 Bacterial infections of the liver
Multifocal necrotizing/suppurative hepatitis
• Fetuses and neonates • Salmonella sp
• Listeria monocytogenes
• Campylobacter spp
• Actinobacillus sp
Abscesses
Granulomas
Morphological patterns
Multifocal
necrosuppurative
hepatitis, tularemia,
beaver.
Salmonellosis, liver, pig (right, bottom). The necrotic foci
are infiltrated by macrophages (paratyphoid nodules).
Pathologic Basis of Veterinary Disease , 4th ed. Multifocal necrotizing hepatitis, necrobacillosis, sheep
From Noah’s arkive
7.2.1 Liver abscesses
Chemical rumenitis & traumatic reticulitis (cattle)
Single or multiple
Commonly involved agents: • Fusobacterium necrophorum
• Corynebacterium pseudotuberculosis
• Trueperella (Arcanobacterium) pyogenes
• Streptococci and Staphylococci
• Rhodococcus equi
Trueperella pyogenes infection, liver, cow, Rhodococcus equi infection, liver, goat.
Fusobacterium necrophorum infection, liver, lamb.
Pathologic Basis of Veterinary Disease , 5thed., Mosby-Elsevier
Liver abscesses Outcome
• Incidental finding
• Become encapsulated and sterile
• Cause fibrous adhesions
• Break into hepatic vein or vena cava Thrombophlebitis
Endocarditis
Pulmonary aneurisms
Lung abscesses
• Generalized infection in young
• Rupture and toxemia
Liver abscess (A) with rupture into an hepatic vein (v), cow
Vena cava thrombophlebitis (left, T) and pulmonary emboli (right, arrows), secondary to liver abscessation, cow
Pathologic Basis of Veterinary Disease, 5th ed., Mosby-Elsevier
A
V
T
Hepatic granulomas
Mycobacteriosis (Tuberculosis)
Epithelioid macrophages laden with Mycobacterium
avium (M) around a blood vessel (V), dog
Hepatic granulomas, bovine tuberculosis (left, top and bottom)
M
V
Pathologic Basis of Veterinary Disease, 5thed., Mosby-Elsevier
7.2.2 Bacillary hemoglobinuria
Etio: Clostridium hemolyticum
Cattle & sheep
Pathogenesis: Liver injury by migrating flukes
anaerobiosis spore germination
exotoxins liver necrosis / intravascular hemolysis hemoglobinuria
Lesion
• Single large area of necrosis
• Rapid autolysis
Single large area of necrosis due to C. hemolyticum (top).
Focal hepatic necrosis, black disease, sheep (bottom).
7.2.3 Black disease of sheep
Syn: Infectious necrotic hepatitis
Etio: Clostridium novyi
Multifocal necrosis
Subcutaneous congestion
Downloaded from Noah’s arkive
7.2.4 Tyzzer's disease
Etio: Clostridium piliforme
• Rodents,
• Immunocompromised or young foals, calves, kittens, puppies
Lesions
• Multifocal necrotizing hepatitis
• Necrotizing colitis
Diagnosis
• Bundles of long bacilli in hepatocytes
• Silver stain (Warthin-Starry)
Multifocal hepatitis, foal. Cl. piliforme infection
Pathologic Basis of Veterinary Disease, 5thed., Mosby-Elsevier
Tyzzer’s disease (Clostridium piliforme). Liver,
horse. Disseminated gray-white 1- to 2-mm foci of
necrosis and by suppurative inflammation.
Downloaded from Noah’s arkive
B. Tyzzer’s disease (Clostridium piliforme),
liver, foal. Note the haphazard distribution
of filamentous bacteria in the cytoplasm of
hepatocytes (arrow). Giemsa stain.
C. Foal. Clostridium piliforme can be
readily seen with special stains such as
Warthin-Starry (arrows)
Pathologic Basis of Veterinary Disease, 5thed., Mosby-Elsevier
Other bacterial and mycotic diseases
7.2.5 Leptospirosis
7.3 Mycotic hepatitis
• Hemorrhagic infarcts
• Granulomatous hepatitis
• Blastomyces spp
• Histoplasma spp Dissociation of hepatic cords, leptospirosis, dog
Yeasts of Histoplasma in the cytoplasm
of Kupffer cells and macrophages
Pathologic Basis of Veterinary Disease (2006), 4th ed., Mosby-Elsevier. Liver infarcts, mycotic infection, cow
7.4.1 Nematodes Ascaris suum
• “Milk spots" in pigs
• Multifocal fibrosis
• Tunnel hemorrhage eosinophilic infiltration/coagulative necrosis fibrosis
Stephanurus dentatus – pigs
7.4 Parasitic diseases of liver
Milk spots, liver, pig Adult forms of Ascaris suum in bile ducts, pig
Dirofilariasis, vena caval syndrome, dog. Several
adult forms of Dirofilaria immitis are present in the
caudal vena cava. Larval migration, liver, equine
Strongylus vulgaris - horses •Migration of larvae •Associated with perihepatitis filamentosa??
Calodium (Capillaria) hepatica - dogs, rodents (adults and eggs in liver) Dirofilaria immitis (heartworm)
•Fatal vena caval syndrome in heavy infections
Granulomatous hepatitis, Capillaria hepatica,
pen-tail bettong (rat-kangaroo). From Noah’s arkive
7.4.2 Cestodes
Ecchinonoccus granulosus
(Hydatidosis)
• Cysts in multiple species
• Adults in carnivores
• Uncommon in Canada
Stilesia hepatica
Thysanosoma actinoides
Cysticercus tenuicollis.
Hydatidosis, pig
C. tenuicollis (T. hydatigena), liver, pig
Thysanosoma,
sheep
7.4.3 Trematodes
Species • Fasciola hepatica, F. gigantica,
Fascioloides magna and Dicrocoelium - ruminants
• Opisthorchis and Platynosomun - dogs and cats
Most significant • F. hepatica & F. gigantica – in bile
ducts
• Fascioloides magna - cavitations within liver parenchyma
Chronic cholangitis due to Fasciola hepatica, liver, cow.
Fasciola hepatica
Chronic cholangitohepatitis and severe parenchymal fibrosis
due to Fasciola hepatica, liver, ox.
Liver flukes LESIONS:
• Immature flukes: trauma during migration (clostridial infections)
• Adults: mechanical and chemical irritation; physical obstruction
fibrosing cholangitis / hepatitis
pipestem liver
Black pigment with F. magna
Blood loss
Migratory tracts of Fasciola hepatica, liver, sheep
Pipestem liver, Fasciola hepatica, cow
Parenchymal, encapsulated, cavitated lesions , Fascioloides
magna, liver, caribou. Note the black excretory pigment
(hematin) deposited by the fluke.
7.4.4 Protozoa
Coccidiosis (rabbits)
Leishmaniasis
Toxoplasmosis
Neosporosis
Histomoniasis in turkeys
Proliferative cholangitis, gross (top) and histo
(bottom), Eimeria stiedae (arrows), rabbit
Histomoniasis, liver, turkey. Well-defined rounded areas of necrosis
VIII. Toxic-induced liver disease
Liver, most common site of toxic
injury
• Toxic agents GIT liver
• Biotransformation of endogenous and
exogenous substances for excretion.
• Bioactivation more toxic
Most agents are predictable, a few
are idiosyncratic
Lesions:
• Acute: Hydropic degeneration,
steatosis & necrosis, often
centrilobular
• Chronic: Fibrosis, biliary hyperplasia
and nodular regeneration
Diffuse fibrosis and nodular regeneration, primidone toxicity, liver, dog
Centrilobular coagulative necrosis (N), liver, marmoset.
P = normal parenchyma (P), central vein (c)
Images from Noah’s arkive
P
N
c
Classification of hepatotoxic liver
injury
Biotransformation cytochrome p450
system (in centrilobular area)
Stimulation of autoimmunity
Stimulation of apoptosis
Disruption of calcium homeostasis
Canalicular injury
Mitochondrial injury
Hepatotoxic agents
Numerous
• Phytotoxins
• Mycotoxins
• Chemicals
• Some therapeutic
agents
Centrilobular necrosis (red areas), liver, bovine
From Noah’s arkive
8.1 Toxic plants
8.1.1 Pyrrolizidine alkaloid poisoning
Common genera: Senecio and Crotalaria
Worldwide (pigs, cattle, horses, goats & sheep)
Alkaloids cytochrome p450 system pyrrolic esters.
Milk sucklings
Lesions
• Acute - centrilobular necrosis
• Chronic - fibrosis (Hepatic veno-occlusive disease)
• Megalocytosis (antimitotic effects)
Senecio vulgaris (Downloaded from Wikimedia
Commons)
Pyrrolizidine alkaloid poisoning – liver
Giant hypertrophy of hepatocytes (Megalocytosis) (arrow) and hyperplasia of biliary epithelium (arrowhead)
Finely nodular liver (minimal parenchymal regeneration)
Veno-occlusive disease. A reticulin stain reveals the marked
deposition of collagen within the lumen of the central vein.
Robbins and Cotran Pathologic Basis of Disease
(2010), 8th ed., Elsevier, Inc. chaper 18
Pathologic Basis of Veterinary Disease, 4 and 5th eds., Mosby-Elsevier Downloaded from Noah’s arkive
8.1.2 Cycads
Contain nontoxic
glycoside (cycasin)
• Deconjugated by intestinal
bacteria
• Bioactivated in liver
Lesions
• similar to pyrrolizidine
alkaloid poisoning (cattle,
sheep and goats)
Dioon mejiae
Ceratozamia kuesteriana
8.1.3 Alsike clover
Trifolium hybridum in
North America
Horses - chronic liver
disease
Histo
• Portal hepatitis and
fibrosis, bile duct
hyperplasia
• Photodynamic dermatitis
Toxic principle unknown (likely a mycotoxin)
www.omafra.gov.on.ca/english/.../info_alsike_clover.htm
Trifolium hybridum
Alsike clover toxicosis, liver, horse.
Extensive fibrosis (F) and marked
bile duct hyperplasia (arrows)
replacing the liver parenchyma (P)
F
P
Noah’s arkive
8.2 Mycotoxins
Secondary metabolites of fungi
Aflatoxins
Sporidesmin
Phomopsin
Poisonous mushrooms
8.2.1 Aflatoxins
Aspergillus flavus
4 major : B1, B2, G1 & G2
B1 - most common & potent (also a carcinogen)
In mouldy feed
Become toxic in hepatocytes
Occurrence • Warm humid temperatures
• Not a major problem in Canada
Pigs, poultry, cattle and dogs
www.mycolog.com/chapter21.htm
Colonies of Aspergillus flavus (yellow)
and Penicillium (green)
http://w3.vet.cornell.edu/nst/nst.asp
Aflatoxins
Acute intoxication (dogs & ducklings)
• Lipidosis/necrosis - centrilobular to massive
• Ducklings - periportal necrosis
Chronic intoxication • Steatosis
• Fibrosis
• Biliary hyperplasia
• Megalocytosis
Aflatoxins are carcinogenic
Pathologic Basis of Veterinary Disease(2006), 4th ed., Mosby-Elsevier.
Chronic aflatoxicosis, pig. The liver is shrunken
and fibrotic from collapse of areas of massive
necrosis and condensation of the fibrous stroma.
Hepatic steatosis, aflatoxicosis (aflatoxin B1), dog
http://www.askjpc.org/wsco/wsc/images/2011/110303-2.jpg
8.2.2 Sporidesmin
Pithomyces chartarum
Dead rye grass; warm climates (New Zealand & Australia)
Unconjugated sporidesmin in bile toxic to biliary epithelium
Lesions • Cholangiohepatitis and cholestasis
• Atrophy of the left hepatic lobe
• Photosensitization in sheep
http://luirig.altervista.org/schedeit/fo/lolium_perenne.htm
Lolium perenne
www.mycology.adelaide.edu.au/images/pitho1.gif
Conidiophores and conidia of
Pithomyces chartarum
Sporidesmin toxicity in sheep. Locally extensive areas of hepatic fibrosis (* top, left) zonal, diffuse hepatocellular
necrosis on cut surface (bottom left); photosensitization (facial eczema); fibrosis and bile duct hyperplasia (histo).
Images from Noah’s arkive.
8.2.3 Phomopsin • Phomopsis leptostromiformis
• Grows on lupins
• Chronic damage :
Small livers, finely nodular (mitotic inhibition and fibrosis)
Photosensitization
More mycotoxins www.mooseyscountrygarden.com/garden-journal-0...
Lupins
Amanita phalloides
8.2.4 Poisonous mushrooms • Amanita phalloides
• Acute damage:
• Lipidosis, hemorrhage, necrosis (centrilobular to massive )
• Toxic cyclopeptides (amatoxin & phalloidin)
Inhibition of RNA polymerase II function
8.3 Blue-green algae
Microcystis aeruginosa (microalga; cyanobacteria)
Grows as blooms on lakes and ponds
Late summer or early fall
Microcystin (preformed toxin)
Lesions • Acute hemorrhagic gastro-enteritis
• Centrilobular to massive necrosis
• Chronic liver disease in survivors
Microcystis bloom
Light micrograph of Microcystis
http://research.myfwc.com/features/view_article.asp
8.4 Hepatotoxic chemicals
Phosphorus
• Vermin control; rodenticide
• Lipidosis and periportal necrosis
(no metabolic transformation)
Carbon tetrachloride (CCl4)
• Fire extinguishers; refrigerants;
cleaning solvents; pesticide;
anthelmintic
• Centrilobular lipidosis and necrosis
Cresols
• Asphalt shingles; clay pigeons
• Massive hepatic hemorrhage and
necrosis in pigs
Metals (Iron, copper)
• Iron-dextran injection in piglets –
massive hepatic necrosis
CCL4 toxicosis, liver cirrhosis (left*) and acquired
portosystemic shunts (tortuous vascular channels), dog
*
8.5 Hepatotoxic therapeutic drugs
Idiosyncratic reactions in a minority of individuals
Species and individual variation • Trimethoprim-sulfonamide - Doberman pinschers
• Carprofen - Labrador retrievers
• Ivermectin - Collies and Shelties
• Acetaminophen – cats (↓ glucuronyltransferase activity)
• Anticonvulsants (primidone, phenytoin and phenobarbital) – end-stage liver.
• Diazepam – acute hepatic failure in cats
Usually centrilobular hepatocytes; unknown mechanisms
Drug-induced cirrhotic livers, dogs (left top &bottom) and cat (right bottom) due to prolonged primidone therapy. RG =
regenerative nodule, PF = portal fibrosis, BF = bridging fibrosis
Hepatocellular necrosis (N), centrilobular,
acetaminophen toxicosis. P = normal parenchyma
http://w3.vet.cornell.edu/nst/nst.asp
N
N
P
P
RN
PF
BF
BF
Downloaded from Noah’s arkive