3 - Liver III Flashcards
What is a viral disease of the liver? What is it caused by?
- Herpesvirus infection
o Bovine, equine, canine, and feline herpesvirus-1
What does a herpesvirus infection cause
- *fetal ABORTION or neonatal death
o Will be autolyzed, but can use histo!
o Equine: FRESH (so can see WHITE SPOTS ON LIVER) - Liver: multifocal haptic necrosis
o *eosinophilic intranuclear inclusions!
What is a bacterial disease of the liver in all species (commonly foals)?
- Tyzzer’s disease
- affects neonates in almost all species
o MOST COMMON in foals
What is the cause of Tyzzer’s disease?
- Clostidium piliforme
o Do silver stain!
What does Tyzzer’s disease cause?
- *multifocal haptic necrosis (white spots)
- Colitis
- Sometimes myocarditis
What is the ideal sample type?
- *FRESH for bacteriology
- Samples in formalin and send for histo
What are other bacteria that cause multifocal hepatic necrosis in neonates?
- EHV-1
- Salmonella
- Rhodococcus
- Listeria
- Arcanobacterium pyogenes
- Many others.
Why take frozen samples?
- Need frozen (unfixed) tissues to isolate viruses
- *if see another xick animal, collect a blood sample
Fusobacterium necrophorum: steps due to grain overload
- Grain overload
- Chemical rumenitis and mucosal injury
- Bacteria enter the portal circulation
- Liver necrosis
- Liver abscess
What is the Fusobacterium necrophorum mixed infection usually with?
- Trueperella pyogenes
- Mucor
Liver abscess are usually incidental UNLESS
- Open into central vein or vena cava and cause PULMONARY THROMBOEMBOLISM
- Cause central vein THROMBOSIS and OCCLUSION causing hepatic passive congestion and portal hypertension
What does neonatal umbilical infection cause in a wide variety of animals?
- *causes multifocal hepatic necrosis or abscesses
- *Multiple causes (mixed infections are common)
Neonatal umbilical infection: sheep
- Campylobacter
Neonatal umbilical infection: calves
- T. pyogenes
- F. necroforum
Neonatal umbilical infection: foals
- Rhodococcus equi
*Tuberculosis: caused by and what does it cause
- Caused by Mycobacterium bovis
- causes hepatic granulomas that are CALCIFIED
**Leptospirosis
- From rodents
- *loves the KIDNEY but causes INTRAVASCULAR HEMOLYSIS and HEPATIC necrosis
- *depends on serovar (one can cause abortion)
- **CULTURE THE KIDNEY
Protozoal diseases
- Toxoplasma and neospora can infect liver and cause NECROSIS
Fungal diseases
- Can cause liver GRANULOMAS
- Aspergillus
- Blastomyces
- Coccidioides
- Histoplasma
Ascaris suum and liver
- Larval stages migrate through liver of pigs creating migration tracts
- *tracts heal by fibrosis producing “milk spot liver”
Strongylus in horses and liver
- Produce fibrous tags on capsule=incidental finding
Dirofilarial immitis (vena caval syndrome)
- If large number in vena cava can cause:
o DIC
o intravascular hemolysis
o acute hepatic failure - *blockage leading to severe PASSIVE CONGESTION WITHIN LIVER
Cysticercus cyst on liver (and other organs)
- Food animals and wild herbivores
- Adult stage Taenia is in dogs
Hydatid cyst
- Food animals and wild herbivores
- *much bigger than cysticercus
- Adult stage is Echinococus
Trematodes and the liver
- Fasciola hepatica: biliary system of ruminants
- Fascioloides magna: migrate through the parenchyma of ruminants
- Metorchis: inhabits the bile duct of dogs and cats
Why is the liver a target for toxicity?
- All ingested substances are delivered to liver via portal system
- Liver is metabolically very active (ex. high energy requirement leading to increased susceptibility)
- Anything excreted by kidneys has to be water soluble
a. Liver is primary stie where chemicals are made water soluble (CYP45- enzymes!)
Do toxins cause lesions in all zones within the liver?
- Can cause random and zonal lesion
- *most common pattern of acute liver toxicity is “centrilobular necrosis”
Why is the most common pattern of acute liver toxicity “centrilobular necrosis”?
- Zone with lowest oxygen tension
- Highest concentration of metabolic enzymes
What are the major mechanisms through which toxicity occurs?
- Production of injurious metabolites
- Formation of neoantigens
- Induction of apoptosis
- Injury to cell membranes and activation of proteases
- Disruption of bile secretion
- Mitochondrial damage
Production of injurious metabolites
- Most common mechanism
- Phase I and II enzymes perform action hoping molecules become more water SOLUBLE
- Metabolites act like free radicals or can form adducts with cellular enzymes
- *centrilobular necrosis is commonly seen
Formation of neoantigens (toxins)
- Toxins bind to cellular proteins which are presented on cell surface (macrophages) as NEOANTIGENS
o Attacked by immune cells - *leads to inflammation and cell deat
Induction of apoptosis (toxins): 2 mechanisms
- Directly
- Secondary to activation of apoptotic pathway by immune system (ex. retained bile acids)
Injury to cell membranes and activation of proteases (toxins)
- Net result is increased influx of Ca which activates cellular processes
Disruption of bile secretion (toxin)
- Disrupt bile secreting pumps
Mitochondrial damage (toxins)
- Toxins can effect mitochondrial membranes, enzymes and DNA
- Disrupt ETC
- *result in fatty degeneration or cell death by necrosis or apoptosis
What are the examples of hepatotoxic agents?
- Blue green algae
- Hepatotoxic plants
- Mycotoxins
- Mushroom poisoning
- Copper and iron toxicity
Blue Green Algae: microcystis
- Toxic algae bloom during hot summer on surface of water
- Causes severe CONVULSIONS (neurotoxic) +/- liver damage depending on type of algae
- Usually ACUTE in nature
How do you diagnosis blue green algae toxicity?
- Analysis of stomach content
Pyrrolizidine alkaloid toxicity
- Alkaloid present in plants (ex. Senico, Crotalaria)
- CYP450 metabolism result in toxic metabolites
- Inhibit cell division but NOT DNA synthesis
- **megalocytes (big hepatocytes) histologically
o Can be seen with other things
How do you diagnose pyrrolizidine alkaloid toxicity?
- Usually chronic in nature
- By time lesion and signs develop, very little toxic is left for analysis
- *need to talk to the owner
Alfatoxin
- Mycotoxins: metabolites of fungi
- Food stored at humid conditions allow fungi to proliferate
- *toxicity is similar to Pyrrolizidine Alkaloid
o Chronic and megalocytes
How do you diagnosis aflatoxin?
- Analyze the feed!
Mushroom poisoning
- Acute
- Dogs and cats
- Centrilobular to massive hepatic necrosis
How do you diagnosis mushroom poisoning?
- Finding mushroom in stomach
Copper and iron toxicity
- Usually chronic through FEED
- Cause oxidative damage to liver and necrosis
- *causes INTRAVASCULAR hemolysis
What are the proliferative lesions of the liver?
- Nodular hyperplasia
- Hepatocellular adenoma
- Hepatocellular carcinoma
- Bile duct neoplasia
- Metastatic neoplasms
**Nodular hyperplasia
- Raised nodules on surface of liver of OLD dogs
- NOT significant if DOG is healthy
- NO fibrosis: nodules are yellow, tan or red
- *different from regenerative nodules
Hepatocellular adenoma
- Somewhat large solitary nodule on liver
- *need histology to differentiate from nodular hyperplasia
Hepatocellular carcinoma
- Friable, grey, white or brown masses on surface of liver
- *can metastasize to lung and peritoneum
o Takes a long time
What are the bile duct neoplasms?
- Chollangiocellular adenoma: UNCOMMON
- Chollangiocelllar carcinoma
Chollangiocellular carcinoma - Relatively common in CATS
- UMBILICATED raised lesions (‘depressed centre’)
o Why it is a carcinoma=epithelial origin - Metastasis is very common
Metastatic neoplasm to the liver
- More COMMON than hepatic neoplasia
Equine serum hepatitis (Theiler’s disease)
- Acute centrilobular to massive hepatic necrosis
- Occurs after an injection of a biologic containing equine serum (EQUINE PARVOVIRUS)
- *hepatic failure and hepatic encephalopathy (life threatening!)
What causes bacillary hemoglobinurea in ruminants?
- Clostridium hemolyticum
- (Clostridium novyi type D)
What are the steps of ruminant bacillary hemoglobinurea?
- Clostridial spores are ingested and reside in liver
- Liver injury (fluke migration, liver biopsy) causes HYPOXIA
- Spores germinate and bacteria releases toxins (phospholipase C and beta toxin)
- Acute liver necrosis, hemolytic anemia and hemoglobin urea
What causes infectious necrotic hepatitis (black disease) in ruminants? How is it different from bacillary hemoglobinurea?
- Clostridium novyi type B
- Similar pathogenesis to bacillary hemoglobinurea but NO INTRAVASCULAR HEMOLYSIS
Hepatosis dietetica in pigs
- Acute necrosis and hemorrhage in young, RAPIDLY GROWING pigs
o Centrilobular to massive
What causes hepatosis dietetica in pigs?
- Vitamin E and/or Selenium deficiency
Infectious canine hepatitis, cause and age group
- Canine adenovirus 1
o PREDILECTION FOR ENDOTHELIAL CELLS (systemically sick: diarrhea, vomiting, fever) - *dogs less than 2 years of age (usually unvaccinated)
Infectious canine hepatitis ‘steps’
- Exposure through oral route
- Viremia
- Spread to liver
- *centriolobular hepatic necrosis with intranuclear inclusion bodies
Lymphocytic cholangitis in cats
- Slowly progressive disease of cat >4 years
- UNKNOWN etiology
- Lymphocytic infiltration centered on bile ducts with bile duct HYPERPLASIA and FIBROSIS
What are the disorders of the gallbladder and extrahepatic bile duct?
- Cholelithiasis (gallbladder stones)
- Cholecystitis
- Gall bladder mucocele
- Cystic mucinous hyperplasia
Cholelithiasis (gallbladder stones)
- Bile concretions
- Can block the extrahepatic duct
- EXTRAHEPATIC JAUNDICE
Cholecystitis
- Usually associated with liver disease
- Ascending infection from INTESTINE
- COW: Salmonella Dublin
- DOG: infectious canine hepatitis
- *thickening of wall with EDEMA
Gallbladder mucocele (dogs)
- Gallbladder filled with mucous (dogs)
o Goblet cell hyperplasia
o Surgery to remove it - Can cause biliary obstruction
- *if ruptures=cause severe bile peritonitis
- *NON-SPECIFIC SIGNS OF ILLNESS
Cystic mucinous hyperplasia
- Mucoas thickened with many surface cysts
- *INCIDENTAL FINDING
o But may predispose them to gallbladder mucocele