Hepatobiliary Flashcards
Milk thistle MOA?
Silymarin is active extract
antioxidant, free radical scavenger, inhibits lipid peroxidation, retards hepatic collagen formation
What are branch chain AAs?
valine
leucine
isoleucine
SAMe MOA?
hepatoprotectice
antioxidant
antiinflammatory
precursor to glutathione
ALT half life in dogs vs cats?
dog: 17-60 h
cat: 3.5 h
Ursodeoxycholic acid MOA?
antiinflammatory immunomodulation antifibrotic promotes choleresis decreases toxic effects of bile acids
zinc MOA
- essential trace mineral
- enhances ureagenesis
- increased glutathione peroxidase activity
- antifibrotic
Histologic lesion most common for drug/toxin hepatopathy?
centrilobular necrosis
How is ammonia produced?
End product of AA, purine, and amine breakdown by bacteria, metabolism of glutamine by enterocytes, and breakdown of urea by bacterial ureases
Ammonia is rapidly converted to ____ in the liver.
urea or glutamine
What does alkalosis cause with HE?
Pushes NH4+ to NH3 which can diffuse into the CNS
T/F: dogs with chronic hepatitis or more likely to have fever and abdominal pain than dogs with active hepatitis
False- acute is painful with fever, chronic more likely to have ascites
T/F: hepatomegaly is more common in acute hepatitis
True
List some mechanisms (pathophys) of hepatocellular injury
tissue hypoxia, lipid peroxidation, intracellular cofactor depletion, intracellular toxin production, cholestatic injury, endotoxic insults, hepatocyte plasma membrane injury
Why are hepatocytes especially susceptible to anoxia?
liver receives a mixture of venous and arterial blood
what does hypoxic damage to the liver lead to?
plasma membrane and cytosolic organelle injury secondary to ATP depletion; free radicals may cause oxidative cellular injury
how does cholestasis injure the liver?
leads to retention of bile acids that directly damages cellular organelles
how do endotoxins damage the liver?
stimulation of inflammatory cells to produce inflammatory mediators (prostaglandins and leukotrienes) that perpetuate inflammation in the liver; TNFalpha plays an important role as well
how does TNFalpha perpetuate hepatitis?
stimulates hepatocyte apoptosis through the Fas-Fas ligand pathway
Name categories and specific diseases causing hepatitis and cholangiohepatitis in dogs and cats
Idiopathic=canine chronic hepatitis, feline cholangitis complex, nonspecific reactive hepatitis
Viral- adenovirus type I, acidophil cell hepatitis, herpesvirus (neonates), FIP
Bacterial- feline cholangitis complex, Lepto, Bartonellosis, Tyzzer’s dz, Salmonellosis, Listeriosis, Tularemia, Brucellosis, Helicobacter, Septicemia, Mycobacteria
Rickettsial- Ehrlichiosis, RMSF
Protozoal- toxo, neospora, leishmania, cytauxzoonosis, hepatozoonosis, coccidiosis
Parasitic- visceral larval migrans, dirofilariasis, liver fluke migration, schistomiasis, echinoccocus cysts
Fungal- Histo, blasto, coccidioides, aspergillosis, phycomycosis
Algal- protothecosis
Hepatotoxins- acetaminophen, aflatoxin, amiodarone, aspirin, azathioprine, azoles, carprofen, diazepam, halothane, methimazole, lomustine, phenobarb, tetracyclines, TMS, xylitol,, zonisamide
What are the two categories of feline cholangitis complex
neutrophilic vs lymphocytic cholangitis
T/F: neutrophilic cholangitis typically appears histologically as neutrophilic infiltration within the wall or lumen of the intrahepatic bile ducts
True
T/F: lymphocytic cholangitis typically appears histologically as neutrophilic infiltration within the wall or lumen of the intrahepatic bile ducts
False- lymphocytic typically is mixed inflammatory infiltrate (lymphocytes +/- plasma cells) within portal areas, associated with varying degrees of fibrosis and bile duct hyperplasia
What can be seen on histopath with chronic neutrophilic hepatitis that is different from acute neutrophilic hepatitis?
varying degrees of fibrosis and bile duct hyperplasia
What underlying conditions can be associated with neutrophilic cholangitis in cats?
IBD, pancreatitis
T/F: liver sampling is preferred over gallbladder bile for C&S in cats with suspect cholangitis?
false- prefer bile
Prognosis for cats with neutrophilic cholangitis? Possible sequelae?
Good prognosis; bile duct obstruction, acute necrotizing pancreatitis, sepsis, MODS
What is the definitive diagnosis for cats with lymphocytic cholangitis? Treatment?
Diagnose using liver biopsy and immunohistochemical staining; tx involved immunosuppressive glucocorticoid therapy
Canine chronic hepatitis is more common in what breeds?
cocker spaniel, bedlington terrier, dalmation, doberman, labrador, standard poodle, westies
T/F: there is evidence that supports an immune mediated process as perpetuating factor for canine chronic hepatitis?
true
what is common on histopath for canine chronic hepatitis?
lymphocytic/plasmacytic inflammation, occasionally neutrophilic, necrosis/apoptosis, evidence of regeneration, fibrosis or hyperplasia of ductal structures
Mainstay of tx for canine chronic hepatitis?
steroids; also other immunomodulatory drugs (ursodeoxycholic acid, metronidazole, azathioprine, cyclosporine)
Prognosis for dogs with chronic hepatitis?
depends on severity- can be excellent with slow progression or poor once cirrhosis develops
What is the role of copper in canine chronic hepatitis?
Unclear; may have elevated copper levels from cholestasis or elevated copper levels may damage hepatocytes; copper chelation has been shown to improve hepatic pathologic findings
Tx for copper induced hepatitis?
D-penicillamine, trientine, reduced dietary copper
Common histopath findings in nonspecific reactive hepatitis?
widespread inflammatory infiltrates (usually lymphocytes/plasma cells) in portal areas and parenchyma in the absence of hepatocellular necrosis
T/F: viral causes of hepatitis carry a fair to good prognosis?
false- it is poor
Pathogen responsible for infectious canine hepatitis?
adenovirus type I- only seen in young, unvaccinated dogs
Histopath findings for canine adenovirus type I?
large3 basophilic to amphophilic intranuclear inclusion bodies within hepatocytes and Kupffer cells (during 1st week of infection)
T/F: when FIP involves the liver, the disease is uniformly fatal
True
Common serovars of Lepto?
icterohaemorrhagiae, canicola, pomona, hardjo, grippotyphosa, bratislava
Which lepto serovars are more likely to have hepatic involvement?
icterohaemorrhagiae and pomona
How often is the liver involved in Lepto infections?
20-35% of cases; most commonly results in acute renal failure
Other organ systems besides liver and kidney that can be affected by Lepto?
uveitis, acute fever, pulmonary hemorrhage
Which hepatic enzyme is affected most severely with Lepto infections?
ALP
Histopath findings in the liver assoc with lepto?
coagulative necrosis, infiltration of lymphocytes and plasma cells
Tx of lepto?
penicillin for leptospiremic stage, doxy for carrier stage (doxy also works for leptospiremic stage)
Peliosis hepatitis and granulomatous hepatitis occur with which type of infectious hepatitis?
Bartonellosis
Preferred method of diagnosis for bartonellosis?
PCR on hepatic biopsy specimens
Tx options for bartonella in dogs?
azithromycin, doxy, enrofloxacin, rifampin
Commonly isolated bacteria in septicemia causing hepatitis?
Staph, Strep, enteric gram - organisms, Clostridium, Fusobacterium, Bacteroides
Possible histopath changes in the liver associated with drugs and toxins?
no changes, cellular swelling, steatosis, necrosis, cholestasis, inflammation, fibrosis
What are the 2 histologic types of cholecystitis in dogs and cats and which is most common?
Neutrophilic cholecystitis (most common) and lymphoplasmacytic follicular cholecystitis
T/F there are no breed predispositions associated with gall bladder disease.
False - Shelties and Cocker Spaniels
What 4 bacterial species are more commonly isolated from dogs or cats with cholecystitis?
E. Coli
Enterococcus sp
Bacteroides sp
Clostridium spp
Bacterial colonization of the bile duct may occur via what 2 mechanisms?
Reflux of duodenal bacteria, or hematogenous spread via the portal vasculature
What are 3 ultrasonographic findings you might expect with cholecystitis in dogs?
Hyper or hypoechoic thickening of the gallbladder wall, distention of the gallbladder and/or cystic duct, echogenic bile
What are the 3 types of necrotizing cholecystitis?
Type 1- areas of necrosis without gallbladder rupture
Type II- acute inflammation with rupture
Type III- chronic inflammation with adhesions and/or fistulae to adjacent organs
T/F -The majority of dogs with necrotizing cholecystitis have had bacterial infection
TRUE
What 4 imaging findings are sensitive indicators of gallbladder rupture?
Presence of echogenic fluid in the gallbladder fossa
Echogenic fluid throughout the abdomen
Echogenic reaction in the pericholecystic region
Radiographic evidence of decreased peritoneal detail
Effusion bilirubin concentration of what compared to serum bilirubin confirms bile peritonitis?
Greater than twice
What is the prognosis for surgical intervention in cholecystitis?
Guarded - high peri operative mortality, long term survival ranged from 61-82%
What are the 2 most common parasites associated with cholecystitis or cholangitis?
Platynosomum concinnum
Ampherimus pseudofelineus
With EHBDO, you would expect the gallbladder and cystic duct to dilate within what time frame and the intrahepatic bile duct to dilate within what time frame?
GB and cystic duct - 24 hours
Intrahepatic duct - 5-7 days
What is the proposed mechanism for development of choleliths in cholecystitis?
Increased gallbladder mucin production and decreased gallbladder motility associated with inflammation
What is the most common composition of choleliths in dogs and cats?
Calcium carbonate and bilirubin pigments
T/F - abdominal ultrasound is the imaging modality of choice to ID choleliths bc radioopaque choleliths are only reported in 24% of dogs and 48% of cats with symptomatic cholelithiasis
False- 48% dogs and 83% cats
List 5 Hepatobiliary disorders associated with EHBDO in dogs and cats
Cholangitis/cholecysitis/choledochitis Gallbladder mucocele Cholelithaisis Neoplasia, cysts Biliary trematode infestation Inspissated bile
List 4 miscellaneous disorders (not pancreatic, duodenal, or hepatobiliary) associated with EHBDO
Regional mass or lymphadopathy
Local peritonitis
Iatrogenic (surgical ligation)
Trauma (stricture/fibrosis)
What has been proposed to be the genetic mechanism of gallbladder mucoceles in Shelties?
Insertion mutation of ABCB4 gene which encodes a protein that translocates phosphotidylcholine from the hepatocyte to the biliary canalicular lumen
What are the expected histopathological findings in a dog with hyperadrenocorticism and a gallbladder mucocele?
Cystic mucinous hyperplasia (in addition to secondary changes such as necrotizing cholecysititis)
What is the hallmark ultrasonographic appearance of a gallbladder mucocele?
Echogenic non-mobile material filling the gallbladder in a stellate or finely striated pattern, often with a hypoechoic rim along the wall
T/F - Bacterial infection of the gallbladder is uncommon in dogs with gallbladder mucocele
True -
T/F Biliary diversion techniques are associated with a worse prognosis and should be avoided
TRUE
What concurrent procedure should be performed at time of cholecystectomy?
Common bile duct must be catheterized and flushed thoroughly to ensure patency
Also submit gallbladder for histopath and aerobic/anaerobic culture and perform liver biopsy
What comprises medical management of a gallbladder mucocele? Is this recommended?
Ursodeoxycholic acid (UCDA) and levothyroxine (reported in 2 dogs, both of whom were hypothyroid), potentially also SAMe, amoxicillin, and omega fatty acids Not recommended due to underlying necrosis of GB wall
List 4 potential benefits of UCDA
Causes choleresis
Immunomodulatory properties
May decrease mucin secretion
May improve gallbladder motility
What is the proposed mechanism regarding gallbladder infarction?
Infarction that may be part of a more generalized hypercoagulable state
T/F - Gallbladder infarction is frequently associated with gallbladder rupture
True - 50% of cases with gallbladder infarction were ruptured at surgery
What histologic findings were reported with gallbladder infarction?
Transmural coagulative necrosis with minimal to absent inflammation
T/F - Bacterial infection is more common in gallbladder infarction than gallbladder mucocele
True - 25% of gallbladder infarction dogs had infection (E.coli or clostridium) vs.
Why is there increased GI ulceration risk with liver failure?
because of decreased gastrin and histamine metabolism and compromised mucosal blood flow caused by potential portal hypertension
what type of PSS is the most commonly reported in dogs and cats?
single extrahepatic, congenital
what is a major contributing factor to worsening hepatic encephalopathy in dogs and cats with PSS and why?
hemorrhage into GI tract, because it acts as a large protein source for more ammonia production
t/f- pica is a common clinical sign reported in PSS patients?
true
what is the major goal of medical therapy for PSS prior to surgery?
decrease production and absorption of ammonia
what type of diet should be recommended for medical management in cases of PSS?
diet high in carbs and low in protein to decrease the building blocks for ammonia production; dairy and vegetable protein sources are less likely to cause worsening of HE compared to meat source proteins
how do abx help in the medical management of PSS?
reduce the number of bacteria available for producing ammonia
what 3 abx concentrate in the GI tract that are recommended for PSS medical management?
metronidazole, neomycin, amoxicillin
how are cathartics useful in PSS medical management?
they increase transit thru the GI tract and trap ammonium ions in the lumen, reducing ammonia absorption
what are the recommended options for fluid therapy since PSS patients often have hypoalbuminemia of chronic disease?
plasma or judicious synthetic colloids (ideally vetstarch >hetastarch)
what are 3 indications for using plasma transfusion for PSS dogs?
support intravascular volume, help maintain COP and provide coag factors
briefly summarize the 2 studies evaluating preoperative anticonvulsant therapy in dogs with PSS
One showed prophylactic anticonvulsants didn’t reduce risk of postop neurologic signs but may have decreased their severity
The other showed using keppra was protective against the development of postop seizures (when starting >24 hrs prior to surgery)
Commonly used anticonvulsants and their doses for mgmt of PSS?
keppra 20 mg/kg PO q 8
phenobarbital 1-3 mg/kg PO q12 hrs
KBr loading dose 100 mg/kg POq6 x 4 doses, then 60-100 mg/kg SID
what is the criteria for determining a safe degree of PSS attenuation during surgery?
increase in portal pressure with temporary complete PSS attenuation of <10 cm H2O
what complication can occur if the portal pressure is >10 cm H2O with complete attenuation of the shunting vessel?
portal hypertension
what 2 devices can be used for gradual PSS occlusion?
ameroid ring constrictor and cellophane band
T/F- intrahepatic PSS are often large and patients may only tolerate partial PSS Ligation?
true; they are at higher risk for portal hypertension with excessive attenuation
what laboratory parameters are most impt to monitor in postop PSS patient?
PCV, TP, glucose, lactate, electrolytes, acid-base
what clinical parameters are recommended to monitor in the postop PSS patient?
HR, RR, temp, ABP, CVP, ECG, UOP, abdominal circumference, intraabdominal pressure, mentation/neuro status
what are the 3 major postop complications associated with PSS patients?
portal hypertension, coagulopathy, neurologic complications
what coagulation parameter has been shown to be increased in patients with PSS compared to healthy dogs?
aPTT
what is the range of reported incidence for dvlpmt of neuro complications in dogs with surgical PSS?
5-12%
reported incidence of cats with surgical PSS correction that develop neurologic signs?
37%, but 56% of them had resolution of neurologic signs
list some possible reasons/mechanisms that animals develop neurologic signs after attenuation of a PSS
- GI hemorrhage from portal hypertension
- abrupt decrease in GABA, aromatic amino acids and endogenous benzodiazepines once shunt has been attenuated
- systemic inflammation and oxidative stress, increased C reactive protein
T/F- there is no scientifically evaluated anticonvulsant therapy protocol for PSS patients and thus no proven benefit of one vs another
true
what is the perioperative mortality rate for extrahepatic PSS repaired using gradual attenuation?
5.5-7.1%
what is assoc with a worse prognosis in dogs with extrahepatic PSS?
lower WBC count and postop complications
mortality rate for dogs with intrahepatic PSS?
12.5%
predictors of short term outcome for dogs with intrahepatic PSS attenuation?
body weight, TP, albumin, and BUN
4 sources of ammonia?
degradation of intestinal protein and urea and colon by urease-producing microorganisms
intrahepatic degradation of AA from diet
enterocyte metabolism of glutamine
muscle catabolism
