Pathology of the Hepatobiliary System #5 Flashcards
Toxic Hepatic Disease
* Liver is common site of ______ injury
* Blood from the ___ vein and ________ circulation
* ___________ site
* General aspects
* Intrinsic (predictable) vs idiosyncratic (unpredictable) hepatotoxins
- Liver is common site of toxic injury
- Blood from the portal vein and systemic circulation
- Biotransformation site
- General aspects
- Intrinsic (predictable) vs idiosyncratic (unpredictable) hepatotoxins
Describe biotransformation.
There are 3 phases.
Phase 1:
- mediated by _________ ______ enzymes
- chemicals are bioactivated to a very ______ energy reactive intermediate molecule.
Phase 2:
- molecules undergo different processes and are __________.
- form a _____ soluble metabolite which can be ______ by the body.
Phase 3:
- _________ process
- translocation of molecule from cell ________ into ________ (in bet. hepatocytes).
There are 3 phases.
Phase 1:
- mediated by cytochrome p450 enzymes
- chemicals are bioactivated to a very high energy reactive intermediate molecule.
Phase 2:
- molecules undergo different processes and are conjugated.
- form a water soluble metabolite which can be excreted by the body.
Phase 3:
- elimination process
- translocation of molecule from cell membrane into caniliculi (in bet. hepatocytes).
This is how drug or xenobiotic is metabolized and biotransformed in the liver.
List the intrinsic hepatotoxins.
- Dose-related
- lower dose, less clinical signs and vice versa - Predictable
- Reproducible
- if we see this in an animal, you can do an experiment in lab animals and see the same effect. - Underlying mechanism understood
- Majority are converted to reactive metabolites
- E.g. acetaminophen
- This is one type of NSAID.
- a higher concentration in animals and humans –> toxic injury b/c lover has to metabolize this drug and if you take too much –> damage
- cats are especially sensitive.
List the idiosyncratic hepatotoxins
- Not necessarily dose-related
- Unpredictable
- Occur in a small percentage of exposed individuals
- Unknown mechanism
- Hypersensitivity related (drug allergy)
- Toxic metabolite-dependent
- E.g. diazepam
- some cats are sensitive to this drug –> can cause unpredictable effect
Acute hepatotoxicity
* Gross: ______ to _____ necrosis
* Histopathology: often characterized by ________ necrosis with ____________
- this is the most common sign
* Example: _______ poisoning in dogs
- xylitol poisoning is another example.
- Why is this not chronic? B/c they get acute hepatotoxicity and die.
zonal, massive, centrilobular, hemorrhage, Mushroom
Chronic hepatotoxicity
* Gross and histopathology: many ________, including ?
* Example: ________ in pigs
- loaded? animal may not die, but this will happen for awhile –> decreased liver function, fibrosis, cerrosis, etc.
patterns
necrosis, inflammation, lipidosis, cirrhosis, atrophy, etc.
aflatoxicosis
List some drugs that are hepatotoxins.
Drugs:
* Antibiotics (e.g. trimethoprim-sulfonamide)
* Anticonvulsant drug (e.g. primidone, phenytoin, and phenobarbital in dogs)
* NSAIDS
* Diazepam (cat)
* Acetaminophem (cat)
* Xylitol (dog)
List some plants or environmental toxins that are hepatotoxins
Plants or environmental toxins:
* Amanitins in dogs(in mushroom Amanita)
* Pyrrolizidine alkaloid in ruminants (in plants like Senecio genera)
- ruminants or sometimes horses are exposed.
- can be found in the field
- chronic hepatotoxicity
fibrosis, cerrosis in the liver b/c you eat grass —> small amt of toxins every day that accumulate over a longer period of time
* Aflatoxin in pigs (in fungus Aspergillus flavus)
- this is a pathogen but can also be found in environment as well. if gran is exposed to aspergillus, there is aflatoxin in grain potentially. if fed for longer period of time –> chronic
Is the color normal? Why?
Acute massive hepatic necrosis in a dog with Amanitin poisoning
No, it is too red. Bright red. Diffuse –> massive necrosis with hemorrhage. The entire liver is dead, which is why it is diffusely dead.
Acute toxic hepatic injury is often characterized by centrilobular necrosis
Centrilobular Necrosis, Zonal Hepatocellular Injury, Liver, Pig.
Centrilobular region is pale = necrosis
Chronic hepatic aflatoxicosis, Pig.
Color is normal, rounded edges, texture is different. Wrinkly why? Scar tissue aka fibrosis = White tracks
this is from chronic grazing
Chronic primidone toxicity in a dog
Nodular regeneration, not neoplastic, but these are regenerative b/c too much damage to the liver.
Primidone is an anticonvulsant medication.
People should still monitor liver enzyme while on these meds
Xylitol Toxicity in Dogs
* Found in ?
* Blood work: ______ and _________
* Histopathology: acute severe hepatic _______ to _______ necrosis
Xylitol Toxicity in Dogs
* Found in gums, baked goods, toiletry products (e.g., facial care products, toothpastes, lip balm) and some medications etc.
* Blood work: hypoglycemia and hyperinsulinemia
* Histopathology: acute severe hepatic centrilobular to massive necrosis
Pyrrolizidine alkaloid toxicosis
Chronic Pyrrolizidine Hepatotoxicity in a Horse
This is a close up of the liver.
Many nodules, leathery in appearance
Grazing on plants containing pyrrolizidine alkaloid.
Hyperplastic and Neoplastic Lesions
Hyperplastic
1. Nodular hyperplasia
- incidental in ___, not seen in many other species
Neoplastic (if not hyperplastic, could be neoplastic).
1. Hepatocellular _________
2. Hepatocellular _________
3. Sarcomas
- Rare; except for ________ in dogs which is often metastatic
4. Metastatic
- E.g.?
Hyperplastic and Neoplastic Lesions
Hyperplastic
* Nodular hyperplasia
- incidental in dogs, not seen in many other species
Neoplastic (if not hyperplastic, could be neoplastic).
* Hepatocellular adenomas
* Hepatocellular carcinomas
* Sarcomas
* Rare; except for hemangiosarcoma in dogs which is often metastatic
* Metastatic
* Lymphoma, hemangiosarcoma, carcinomas (from pancreas,
gastrointestinal tracts, etc.)
Hepatic Nodular Hyperplasia, Liver, Dog.
incidnetal finding in a dog, probably not clinically significant
Hepatocellular adenoma, Liver, Dog
Well circumscribed nodule, composed of proliferatin hepatocytes.
Histologically will bale to tell the difference between nodule and hyperplasia.
Hepatocellular carcinoma, Liver, Dog.
Carcinomas can metastatize! problem!
not well circumscribed -> metabolized to peripheral tissue
- on histo can see increased mitotic figures, atypical cells, etc.
Hemangiosarcoma, Metastases, Liver, Dog.
Metastatic cancer
can tell this is metastatic b/c it is multifocal. with a primary tumor you usually see a solitary tumor.
Hemangiosarcoma is a metaplasia of endothelium, and every organ has endothelium.
As a general rule = single site
Mutliple site = metastatc; need to go find primary lesion whichis iehter in spleen or right orical which is where we typically see hemangiosarcoma
Hepatic Lymphoma, Liver.
Multifocal white nodules.
Gross exam: nodules are pale tan in color–> round cell tumor indicative or mast cell tumor
Which species do not have a gallbladder?
Species that don’t have gallbladder: horses, cervids, elephants, giraffes, rats, camelids, pigeons
How does bile flow?
- Bile flows in same direction as _____ and _______ direction of blood
- Biliary canaliculi → Intrahepatic ductules → Interlobular ducts → Hepatic ducts → Hepatic duct + cystic duct of gallbladder → Common bile duct → duodenum
- Bile flows in same direction as lymph and opposite direction of blood
Species without gallbladder can have stones in these ducts.
Stones are secretions or precipitates in these tracts.
not gallbladder that produces stones, just precipitants from these tract
