Exam 3 - Canine Liver Disease Flashcards
what is the first question you should ask yourself if your patient is showing clinical signs commonly seen in hepatic disease?
is the liver actually diseased
what if your patient has non-specific signs that may or may not reflect hepatic disease? how will you differentiate hepatopathy with vague signs from non-hepatic disease with vague signs?
CLIN PATH!!!!!!!!!!
why can you not expect to see abnormalities in all the panel tests in a patient with significant hepatic disease?
disruption of one hepatic function doesn’t necessitate the disruption of another
T/F: sometimes there are no laboratory changes seen despite major hepatic disease
true
T/F: cholestasis indicates that there is a blocked bile duct when ALP is elevated on the chemistry panel
false - it can be caused by bile duct obstruction from intra-hepatic & extra-hepatic obstruction, but ALP can also be elevated due to drugs (corticosteroids, phenobarbital, primidone)
what are some reasons for ALP to be elevated in a dog?
canine ALP can be elevated due to hepatic disease, extrahepatic biliary obstruction, & endogenous/exogenous steroids
T/F: any increase in ALP in a cat indicates significant disease
true
why may ALP be elevated in a cat?
significant hepatic disease, diabetes mellitus, & hyperthyroidism
what is probably the most common sign seen in animals with hepatic disease?
anorexia
what lab abnormality can sometimes be responsible for CNS signs & mimic encephalopathy?
hypoglycemia
T/F: PU/PD is relatively common in severe hepatic insufficiency, such as animals with portosystemic shunts
true
ascites may be due to ________ or _________ or both
hypoalbuminemia
portal hypertension
what is the classic presentation of an animal with encephalopathy?
animal eats something & starts acting weird 1-3 hours later (CNS signs)
why may we see coagulopathy in animals with hepatic disease?
the liver is where coagulation factors are produced - also easy to cause DIC in organs with slow sinusoidal blood flow
ALT is a very sensitive test of what?
hepatocellular membrane integrity
T/F: normal ALT/ALP eliminates the possibility of hepatic disease
false
T/F: ALT & ALP activities are specific for certain hepatic disorders & you can tell what hepatic disease is occurring based on these values
FALSE - not specific!!!!!!
if you are convinced that there is hepatobiliary disease in your patient, what would be a good way to differentiate between hepatocellular icterus from extrahepatic biliary tract obstruction?
do an abdominal ultrasound looking for evidence of obstruction
T/F: when trying to answer the first question on whether your patient’s liver is diseased, at least one of the diagnostic tests run (chemistry/radiographs/ultrasound/liver function tests) will almost always be abnormal
true
what is the second question you should ask after deciding if the patient’s liver is diseased?
is the hepatic disease clinically important - need to see if the hepatic disease is the CAUSE of the animal’s illness (primary hepatic disease) or if it is the result of the animal’s illness (hepatic disease secondary to other problems)
what is the most common radiographic pattern seen in dogs & cats with hepatic disease? is it helpful?
symmetric hepatomegaly - doesn’t help when trying to determine if the liver disease is important because both primary & clinically insignificant secondary disease may have it
what are some clinical signs associated with liver disease?
anorexia, weight loss, vomiting, PU/PD, ascites, icterus, encephalopathy, & coagulopathy
what are your liver enzyme markers for hepatocellular damage? what are your enzyme markers of cholestasis?
hepatocellular damage - ALT & AST
cholestasis - ALP & GGT
T/F: severe increases in ALT indicates there is irreversible liver damage
false
where is ALT found in the body?
primarily found in the cytosol of hepatocytes making it virtually liver specific
when is ALT released by the liver? can drugs affect this enzyme level?
with increased membrane permeability or hepatocellular necrosis
yes - corticosteroids & phenobarbital can cause mild increases
what are 2 examples of ALT elevations that indicate the need for further investigation?
severely or persistently elevated!!!
single value is >3x the upper limit of normal
value is 2x greater than the upper limit of the reference interval for 4 weeks
T/F: ALT can be increased due to both primary or secondary liver injury
true
what are examples of drugs that can cause elevation of ALT in dogs?
corticosteroids & phenobarbital
what are some examples of primary hepatopathies causing increased ALT?
inflammatory, neoplasia, infectious, trauma, hyperplastic nodules, & vascular issue
what are some examples of secondary hepatopathies causing increased ALT?
endocrine problem, inflammatory disease, hypoxia, & metabolic issue
why is AST less liver specific than ALT as a marker of hepatocellular damage?
it is found in the cytosol & mitochondria of hepatocytes (I think muscle cells too) - can be increased with myopathies!!!
T/F: increases in AST parallel those of ALT which explains why corticosteroids & phenobarbital can cause mild increases in both
true
what are the 2 main isoforms of the non-specific ALP gene?
liver & bone!!!!
what is the intestinal ALP gene that is clinically important to consider in dogs?
glucocorticoid induced isoform of ALP
where is ALP found in the body?
it is bound to the membranes of the hepatocytes that form the bile canaliculi & sinusoids
what is ALP a sensitive marker for? is it liver specific?
cholestasis - both intrahepatic & extrahepatic disease
not liver specific
T/F: increases in serum ALP may not be clinically significant in dogs
true
what are some examples of why the bone isoform of ALP may cause increased serum levels?
growth, osteolytic disease, hyperparathyroidism, & idiopathic
what are some examples of why the steroid isoform of ALP may cause increased serum levels?
iatrogenic
hyperadrenocorticism
what are some examples of why the liver isoform of ALP may cause increased serum levels?
hepatic parenchymal disease - nodular hyperplasia, vacuolar hepatopathy, toxicity, chronic hepatitis, & neoplasia
biliary tract disease
extra-hepatic disease
increases in GGT parallel increases in what other enzyme?
ALP
what is GGT a sensitive marker of?
cholestasis
what induces GGT release?
corticosteroids
where is GGT found in the body?
bound to the membrane of the hepatocytes that form the bile canaliculi & bile ducts
also produced by extra-hepatic tissues
after answering whether the liver is diseased, what 2 questions should you consider next?
- is the liver disease clinically important?
- are there any obvious extra-hepatic causes?
what clinical pathology findings may indicate liver dysfunction on a chemistry panel?
decreases in - albumin, cholesterol, glucose, & BUN
increases in - bilirubin
T/F: dogs with severe hepatic disease can have normal liver function tests
true
what tests can you use to evaluate liver function?
preprandial & postprandial serum bile acids
serum ammonia
what are abdominal rads useful for when working up liver disease?
assessing hepatic size
looking for masses
looking for extra-hepatic disease
what is an abdominal ultrasound useful for when working up liver disease?
evaluating the hepatic parenchyma & biliary tract
looking for extra-hepatic disease
T/F: dogs with liver disease can have normal ultrasound evaluations
true
what is the final question you should consider when approaching a liver disease case?
should you biopsy the liver
what does hepatic cytology not allow you to do?
can’t assess hepatocellular architecture
T/F: some liver diseases can be diagnosed based off of a liver FNA/cytology
true
what are 3 possible indications for hepatic biopsy?
- persistently increased serum ALT activities - greater than 2X the upper limit of the reference interval for 4 weeks or more
- evidence of hepatic dysfunction
- hepatic masses
what do you need to do prior to doing a liver biopsy?
assess hemostasis!!!
platelet count
BMBT
coagulation panel
a hepatic biopsy gives you a ___________ diagnosis but not necessarily an ________ diagnosis
histomorphological
etiological
what is the least invasive method of performing a hepatic biopsy? what are the disadvantages to this method?
needle biopsy
small biopsy specimens & not possible to observe hemorrhage
what is the most invasive method of performing a liver biopsy? what are the advantages? disadvantages?
surgical biopsy
advantages - direct visualization of the liver, can observe the liver for hemorrhage, simple to perform, & adequate biopsy specimens
disadvantages - invasive, more expensive
what are the limitations of hepatic biopsies?
invasive - risk of hemorrhage
expensive
susceptible to sampling variation
how do you make the most out of a liver biopsy?
collect adequately sized specimens
collect several biopsies - 5 to 7 for laparoscopic & 3 to 4 for needle/surgical
culture liver and/or bile
keep a frozen sample for copper quantification
what are 3 examples of pre-hepatic icterus in dogs?
hemolysis!!!
primary IMHA
secondary IMHA - babesia, neoplasia
non-immune mediated - onion toxicity
what are 4 examples of hepatic icterus in dogs?
- chronic hepatitis
- toxins - acetaminophen, diazepam, phenols, tetracycline, etc
- neoplasia - lymphoma, hepatocellular tumors
- cholangiohepatitis
what are 4 examples of post-hepatic icterus in dogs?
obstruction
pancreatitis
gall bladder mucocele
biliary rupture
what are the 4 most common causes of icterus in the dog?
- immune-mediated hemolytic anemia
- acute liver injury
- extrahepatic bile duct obstruction
- chronic hepatitis/cirrhosis
when an icteric patient presents, what is the first question to consider? where do you go from there?
is the patient anemic or not!
if anemic - explore causes
if not anemic - abdominal ultrasound
what is the most common histological lesion of the canine liver? why? what would you expect to see on the chemistry panel?
vacuolar hepatopathy - can be caused by endogenous/exogenous glucocorticoids (often cause not apparent)
ALP much higher than ALT!!
why does vacuolar hepatopathy provide limited clinical significance?
it really only indicates the possibility of corticosteroid excess
can progress to hepatocellular carcinoma in scottish terriers
what lesion is seen in this photo of an FNA from a dog’s liver?
vacuolar hepatopathy from glycogen deposition
what are some examples of toxins/drugs that can cause acute liver injury?
sago palm, xylitol, acetaminophen, phenobarbital, sulfa drugs, carprofen
what is the general goal in treating a patient with acute liver disease?
identify the cause & prevent further exposure
treat underlying conditions if possible - prevent/reduce exposure, use antitoxins, & treat infectious agents
supportive care if indicated
what antidotes are used for amanita toxicity?
silymarin or penicillin G
what antidote is used for acetaminophen toxicity?
n-acetylcysteine
what are the general categories of causes of primary hepatitis in dogs?
- idiopathic
- copper-associated
- lobular dissecting
- eosinophilic
- granulomatous
why are reasons why copper may accumulate in the liver in copper-associated chronic hepatitis? why does too much copper cause problems?
- defect in copper metabolism
- cholestasis
- excess dietary copper
liver is the principal recipient of copper & free copper ions lead to the formation of hydroxyl radicals
what dog breed is at risk for copper-hepatopathy? why?
bedlington terrier
autosomal recessive - deletion in the COMMD1 gene that encodes a copper exporter leading to massive centrilobular copper accumulation that occurs with resulting necrosis
what are some potential causes of granulomatous hepatitis?
fungal disease
schistosomiasis
bartonellosis
mycobacteria
what is seen in this photo? what kind of hepatopathy does it cause?
canine schistosomiasis - granulomatous hepatitis
T/F: most toxins & drugs cause acute liver injury rather than chronic hepatitis
true
what is a viral cause of liver disease in dogs?
canine adenovirus-1
tends to cause acute disease
T/F: autoimmune liver diseases are suspected to be the cause of chronic hepatitis in certain dog breeds but not proven
true
what dog breeds are associated with the belief of autoimmunity playing a role in liver disease?
dobermans
english springer spaniels
cocker spaniels
why are dogs with copper associated chronic hepatitis often subclinical?
copper accumulation occurs before hepatic lesions do & the liver has a large functional reserve capacity
what are the earliest & most consistent lab values observed in dogs with copper associated chronic hepatitis?
increased ALT & ALP
increased bile acids & ammonia are relatively insensitive
how is copper associated chronic hepatitis diagnosed?
freeze a specimen of the liver in a metal free plastic container - avoid sampling regenerative nodules
need a minimum of 50mg (wet weight) of tissue - 1cm, 14G tru-cut biopsy
submit sample for copper quantification
when do you chelate in a dog with copper associated chronic hepatitis? how long do you chelate?
if the hepatic copper content is > 1,500 ppm
the hepatic copper content is > 750 ppm if the copper is centrilobular in distribution
copper staining suggests primary copper accumulation
if initial copper is <1,000 ppm, 6 months
if copper is >1,500 ppm, at least 10 months
what are the most common side effects seen with d-penicillamine?
gi side effects
more serious idiosyncratic reactions also possible
what medication can you not give alongside d-penicillamine when treating a dog with copper hepatopathy?
zinc
what is the purpose of giving zinc to a dog with copper hepatopathy? what do blood levels of zinc indicate?
reduces the absorption of copper
70 ug/dL is normal
200-300 ug/dL reduces copper absorption
1,000 ug/dL causes hemolysis
why do you need to check zinc blood levels when using it to treat copper hepatopathy?
too much zinc causes hemolysis
what is the purpose of modifying a patients diet for treating copper hepatopathy?
used to prevent recurrence in dogs that have undergone chelation - commercial copper restricted & zinc supplemented diets
hepatic copper could be normalized in 50% of subclinical labs managed with diet alone
what are the detrimental effects of using glucocorticoids to treat idiopathic chronic hepatitis?
vacuolar hepatopathy
increases oxidative stress
what are the benefits of using pred for treating idiopathic chronic hepatitis?
decreased inflammation in some dogs & improved survival seen in some retrospective studies
what are the benefits of using cyclosporine for chronic idiopathic hepatitis? what dosing is used?
alternative to using pred - 5 mg/kg/day PO
can still track liver enzyme activities
why is the liver susceptible to oxidative injury?
plays a large role in the metabolism of drugs & toxins
its location between the splanchnic & systemic circulations
large resident pool of macrophages
what are some indications for using SAMe in a dog or cat?
acute liver injury in either dog or cat
canine chronic hepatitis
feline hepatic lipidosis
what is the purpose of using SAMe for patients with liver disease?
precursor of glutathione - dosed at 20 mg/kg daily on an empty stomach
antioxidant
anti-inflammatory properties
modulates apoptosis
what is silymarin? what are the benefits in using it for a patient with liver disease?
mixture of 7 flavanolignans extracted from the milk thistle plant
antioxidant, anti-inflammatory, anti-fibrotic, & choleretic
why is denamarin prescribed alongside lomustine chemotherapy?
lomustine damages the liver - so dogs treated with it commonly have elevations in their liver enzymes
use of denamarin (SAMe & silyphos) reduces these changes & dogs treated with denamarin were more likely to finish their chemotherapy
what are some indications for using silymarin in a dog or cat? what dose is used?
acute injury in dogs & cats - especially amanita toxicity
possibly chronic hepatitis in dogs
3-6 mg/kg PO daily
why are some possible indications for using vitamin E for a patient with liver disease? what is the dosing used?
acute livery injury in dogs & cats
chronic hepatitis in dogs
feline hepatic lipidosis
15 IU/kg PO daily ideally given with food
T/F: there is no clinical evidence supporting the use of vitamin E in dogs & cats with hepatic disease
true
what is the purpose of prescribing vitamin E for a patient?
acts as an antioxidant - protects phospholipids from oxidative injury by scavenging free radicals
what is the most biologically active form of vitamin E?
a-tocopherol
what are the potential benefits of using ursodeoxycholic acid?
displacement of hydrophobic bile acids
inhibition of hepatocyte apoptosis
choleresis
immunomodulatory effects
what are the suggested uses of ursodeoxycholic acid? what is the dosing used?
cholestatic liver disease in dogs & cats - feline cholangitis & non-obstructed gall bladder mucocele
possibly chronic hepatitis in dogs
10-15 mg/kg PO daily
T/F: a patient prescribed ursodeoxycholic acid will have changes seen on their serum bile acid testing
false - not known to have a big effect
T/F: ursodeoxycholic acid is known to may occasionally cause diarrhea
true
what are the factors involved in the pathogenesis of hepatic encephalopathy?
- ammonia
- manganese
- aromatic amino acids
- oxidative stress
- neurosteroids
- inflammation
how does the decreased metabolism of ammonia lead to hepatic encephalopathy in a patient with liver disease?
the urea cycle in the liver is decreased & the liver receives 85% of the body’s ammonia from portal circulation
with the decreased metabolism, the body doesn’t excrete ammonia appropriately, & there is a build up of ammonia in systemic circulation which causes the signs seen in hepatic encephalopathy
in this photo, this cat has what signs indicating hepatic encephalopathy?
copper colored irises
what are the clinical signs associated with hepatic encephalopathy in dogs?
lethargy, altered behavior, obtundation, ataxia, seizures, ptyalism, head pressing, vomiting, & vision loss
what are the clinical signs associated with hepatic encephalopathy in cats?
copper colored irises
ptyalism
what are some putative precipitating factors of hepatic encephalopathy?
SIRS, hyponatremia, hypokalemia, alkalosis, azotemia, furosemide, diet change, gi hemorrhage, & constipation
what supportive care is indicated for patients with hepatic encephalopathy?
IV fluids - correct dehydration, electrolyte abnormalities, & acid/base
hypoglycemia - monitor
cleansing warm water enemas
T/F: prophylactic use of anticonvulsants prior to corrective shunt surgery is controversial in animals with hepatic encephalopathy
true
what anticonvulsants are commonly used for patients with hepatic encephalopathy?
levetiracetam
phenobarbitol
potassium bromide - dogs only
when will you use anticonvulsants for a patient with liver disease?
hepatic encephalopathy - patient with a history of seizures
how do you treat increased intracranial pressure in animals with hepatic encephalopathy?
mannitol
raise head to 30°
avoid jugular compression
forced ventilation
how do you treat gastrointestinal hemorrhage in a patient with hepatic encephalopathy?
omeprazole
famotidine
sucralfate
why is lactulose used for patients with hepatic encephalopathy? what is the dosing used?
decreases the absorption of ammonia & dose is adjusted until stools are soft - 1-3 mL/kg PO every 6-8 hours
can also be given as a retention enema (1 part lactulose to 3 parts water at 10 ml/kg retained 30 minutes to 1 hour)
what are the adverse effects of using neomycin for a patient with hepatic encephalopathy?
can cause ototoxicity or nephrotoxicity
what antimicrobials are used for patients with hepatic encephalopathy?
neomycin
metronidazole - use a lower dose
amoxicillin/ampicillin
_______ _______ can predispose patients to hepatic encephalopathy, so severe protein-restricted diets are no longer recommended
muscle wasting
how is nutrition approached in a patient with hepatic encephalopathy?
feed a liver support diet initially & add non-meat based protein if the dog tolerates it
what causes portal hypertension? what are the sequelae of portal hypertension?
caused by increased resistance to blood flow in the portal vein
acquired shunts, splenomegaly, & possible gi signs
T/F: never ligate acquired shunts
true
which is easier to find on ultrasound, acquired portosystemic shunts or congenital?
acquired
why do animals develop acquired portosystemic shunts?
vestigial shunting blood vessels open up due to portal hypertension - multiple vessels
what pathology is shown in this photo?
acquired portosystemic shunts
why does ascites develop?
portal hypertension
hypoalbuminemia
activation of the RAAS
what kind of fluid is seen in ascites?
modified transudate
T/F: ascites is a negative prognostic indicator in dogs with chronic hepatitis
true
T/F: dogs with intrahepatic congenital portosystemic shunts are believed to be at a higher risk of gi ulcers
true
what clotting factors are affected when a patient has an increased risk of bleeding?
decreased: FII, FVII, FIX, FX, FXI, dysfibrinogen, platelets
qualitative platelet defects
what clotting factors are affected when a patient has an increased risk of clotting?
increased: FVIII, vWF, fibrinogen
decreased: protein C, protein S, & antithrombin III
T/F: despite coagulation abnormalities in dogs & cats with liver disease, they rarely spontaneously bleed
true
what are some disadvantages of using cyclosporine for idiopathic chronic hepatitis?
can cause gi side effects & gingival hyperplasia
relatively expensive
