Hepatobiliary System, Pt. 5 Flashcards
Why is the liver a common site of toxic injury?
- receives blood from portal vein and systemic circulation
- biotransformation site
What are the 3 phases of hepatic metabolism?
- fat-soluble toxins are activated by oxidation, reduction, hydrolysis, hydration, or dehalogenation by cytochrome P450
- activated metabolites are conjugated by sulfation, glucuronidation, glutathione, acetylation, or methylation into excretable water-soluble waste
- this new product is moved across the cell membrane and reaches the sinusoids/canaliculi for excretion via urine, bile, or stool
What are the 2 categories of hepatotoxins?
- INTRINSIC - predictable, reproducible, dose-related with an understood mechanism where most are converted into reactive metabolites (acetaminophen)
- IDIOSYNCRATIC - unpredictable, non-reproducible (only occurs in a small %), with an unknown mechanism (diazepam)
What are the 2 most probable mechanisms of idiosyncratic hepatotoxins?
- hypersensitivity related (drug allergy)
- toxic metabolite-dependent
How do acute and chronic hepatotoxicity compare?
ACUTE - zonal to massive necrosis characterized by centrilobular necrosis with hemorrhage (mushroom poisoning in dogs)
CHRONIC - many possible patterns including necrosis, inflammation, lipidosis, cirrhosis, atrophy, etc. (aflatoxicosis in pigs)
What drugs are considered hepatotoxins?
- antibiotics (trimethoprim-sulfonamide)
- anticonvulsants (primidone phenytoin, phenobarbital)
- NSAIDs
- diazepam (cat)
- acetaminophen (cat)
- xylitol (dog)
What plants/environmental toxins are considered hepatotoxins?
- amanitins in dogs from Amanita mushrooms (acute)
- pyrrolizidine alkaloid in ruminants from Senecio plants (chronic)
- aflatoxins in pigs from Aspergillus flavus (chronic)
What kind of effect does amanitin have on the liver?
acute massive hepatic necrosis
- dogs
- bright red
- massive hemorrhage
What is acute hepatic injury typically characterized by histologically?
centrilobular necrosis (central pallor)
What kind of effect does aflatoxin have on the liver?
chronic hepatotoxicity
- rounded edges
- wrinkled texture caused by fibrosis with white tracks
- common in pigs and caused by chronic grazing on non-fatal doses of moldy grain/grass
What kind of effect does primidone have on the liver?
chronic hepatotoxicity
- dogs
- multifocal regenerative nodules
What is commonly seen in blood work and histopathology in xylitol toxicity in dogs?
BW - hypoglycemia, hyperinsulinemia (increased release from pancreas)
HP - acute severe hepatic centrilobular to massive necrosis
- necrosis with inflammatory cells
- loss of chord/plate structure
How does pyrrolizidine alkaloid affect the liver?
chronic hepatotoxicity
- multiple leather-like nodules
- common in horses
What 4 neoplastic lesions are seen in the liver?
- hepatocellular adenomas
- hepatocellular carcinomas
- sarcomas - rare, typically metastatic from hemangiosarcoma
- metastatic lymphoma, hemangiosarcoma, and carcinomas from the pancreas, GI, etc.
Hepatic nodular hyperplasia, dog:
- incidental in older dogs
- pale tan well-demarcated nodule that does not compress surrounding tissue
- contain portal triads in nodule
Hepatocellular adenoma, dog:
- similar to hyperplasia
- well-circumscribed proliferation of neoplastic hepatocytes lacking portal triads
Hepatocellular carcinoma, dog:
- arises from liver
- infiltrative into peripheral tissue
- ability to metastasize
Hemangiosarcoma liver metastasis, dog:
- multifocal hemorrhagic nodules
- endothelial origin
(multifocal suggests metastasis; focal suggests primary)
Hepatic lymphoma:
multifocal white-tan nodules
What 7 species lack gallbladders?
- horses
- cervids
- elephants
- giraffes
- rats
- camelids
- pigeons
How does bile flow in the liver?
- biliary canaliculi
- intrahepatic ductules
- interlobular ducts
- hepatic ducts
- cystic duct of gallbladder
- common bile duct
- duodenum
same direction as lymph and opposite of blood
What is the function of the gallbladder? What are 4 sequels to obstruction?
stores and concentrates bile
- hyperbilirubinemia (post-hepatic icterus)
- cholecystitis
- maldigestion of fats resulting in acholic, white/gray feces (stores enzymes for digestion)
- rupture resulting in acute peritonitis
Normal gallbladder histology:
layers = epithelium + submucosa
What is the structure of normal gallbladder epithelium?
(pseudo)columnar ciliated
What is a common incidental finding in feline gallbladders?
bilobed gallbladder - no clinical significance
What are the 4 most common gallbladder lesions?
- mucocele
- infarction
- cholecystitis (commonly secondary to mucocele or obstruction)
- choleliths
What is gallbladder mucocele? What 3 conditions is it commonly associated with? In what animals is it most common?
dilation of the gallbladder with semisolid mucoid secretions
- decreased gallbladder motility
- bile stasis
- altered bile composition and viscosity
dogs
What is the characteristic ultrasound appearance of gallbladder mucocele?
kiwi appearance due to mucoid secretions forming strands within gallbladder
Gallbladder mucocele, dog:
L = distended lumen
R = thick mucoid contents, thickened wall
What hyperplastic and neoplastic lesions are seen in the gallbladder?
cystic mucinous hyperplasia (no significance)
cholangiocellular (biliary) adenoma or carcinoma
Gallbladder cystic mucinous hyperplasia, dog:
mucoid bubbles/pearls representing proliferation of gallbladder mucosa into finger-like projections
What does gallbladder infarction look like grossly?
diffuse dark red discoloration localized in the gallbladder without liver involvement
Choleliths, pig:
concretions can cause a blockage, leading to jaundice or cholecystitis
Choleangiocellular (biliary) cystadenoma, cat:
cystic lesion that doesn’t grow quickly or metastasize
- not a significant clinical finding
What is the characteristic appearance of cholangiocellular (bile duct) carcinoma?
umbilicated (donut-like) lesions of neoplastic biliary epithelium
- bad prognosis —> affects liver function
