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99 Cards in this Set

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What are some histologic characteristics of chronic hepatitis?
hepatocellus apoptosis/necrosis, mononuclear or mixed inflammatory infiltrates, regeneration and (if severe) fibrosis and cirrhosis
What are some breed predispositions for chronic hepatitis?
cocker paniels (male>females)
Labs
Bedlington terriers**
Doberman pinschers (female>male)
Dalmation
Westies**
standard poodles
GSD
Scotties
Beagles
Skye terriers
**common
What age animals does chonic hepatitis affect?
middle aged
Is chronic hepatits more common in dogs or cats?
dogs
True or false: One possible etiology of chronic hepatits is immune-mediated
true
What breed is predisposed to copper accumulation?
Westies
Dobermans
Skye terriers
English springer spaniel
Bedlington
Does secondary copper accumulation in dogs with hepatitis potentiate hepatitis?
Unsure
Does iron accumulation in dogs with chronic hepatitis cause additional inflammation?
Yes
Explain the cycle of fibrosis/cirrhosis
inflammatory cells and mediators cause Hepatocellular necrosis and creates dead speace
Liver responds by producing more hepatocytes and biliary duct epithelium
Inflammatory cells release proteiases/free radicals and damage ECM and cell membranes
Collagen-producing cells are recruited by transforming growth factor
Alterations in ECM + collagen = disarray of hepatocytes and altered function
Fibrows follows tracts of inflammation and necrosis (starts in portal region but will bridge to central vein)
Briding fibrosis = permanent damage = cirrhosis
True or false: hepatocellular fibrosis will lead to portal hypotension
False: leads to portal hypertension (impede ability of vessels to distend => increased resistance)
Are dogs with elevated portal pressures suscepible to ascites?
yes - and hepatic encephalopathy
What type of portal hypertensions are there? (causes)
pre-hepatic
intra-hepatic
Post-hepatic
What does right-sided heart failure lead to in terms of type of portal hypertension
Post-hepatic
Which two types of hepatic cuases of portal hypertension will lead to development of acquired collaterals?
Pre-hepatic
Intra-hepatic
What must the portal pressures be in comparison to systemic pressures be in order for portal collaterals to become patent?
Portal pressures must be increased above systemic pressures
List some causes of intra-hepatic disorders of portal hypertension
cirrhosis
chronic hepatitis
biliar fibrosis
List some causes of pre-hepatic disorders of portal hypertension
portal vein obstruction (thrombus, invasive neoplasia, fibrosis/structure)
extraluminal neoplasia
cyst
abscess
What are two kown toxins that can lead to hepatic encephalopathy if they are not metabolized by the liver?
ammonia and aromatic amino acids
What are some signs of hepatic encephalopathy
lethargy, aggression, head pressing, stupor, coma, seizures and death
In the dog, when will the circulation of toxin cross the BBB?
portosystemic shunting (acquired or congenital)
Do cats require PSS to get hepatic encephalopathy?
nope - hepatic encephalopathy can occur with fasting (arginine deficiency)
What is the most ammoniagenic protein?
Blood - GI bleeding can make encephalopathy worse
What acid base disturbance can exacerbate HE by increasing ammonia production and CNS uptake?
metabolic alkalosis
What element causes a shift extracellulary in exchange for sodium and hydrogen ions?
potassium
Whattype of diuretics are recommended in cases of HE?
potassium-sparing aldosterone receptor antagonizing diuretics
With an animal with ascites, do we want to removal all of the ascetic fluid?
No, it may exacerbate encephalopathy by activating RAAS
what are some clinical signs of chronic hepatitis?
weight loss, anorexia, vomiting, lethargy, PU/PD, weakness and ascites
What breeds of dog can develop cutaneous lesions as a result of chronic hepatitis?
Cockers and westies
What are some things you will find on PE of a dog with chronic hepatitis?
distended abdomen, poor BCS and icterus (rarely)
What will be on a CBC/chem of a dog with chronic hepatitis?
anemia of chronic disease
typically moderate to severe elevations in ALT and moderate elevations in ALP
decreased BUN
Decreased cholesterol
Decreased albumin
decreased clotting factors
Decreased glucose
In an animal with chronic hepatitis, what would be the PT and PTT of an animal with a guarded prognosis?
increased
Does chronic hepatitis cause hepatomegaly or microhepatica?
Microhepatica
How do you diagnose chronic hepatitis?
biopsy (typically surgical or laparoscopic due to size)
Are vacuolar changes common in animals with chronic hepatitis?
Yes - due to endogenous corticosteroids
What type of liver tissue is needed for quantification analysis of copper
fresh tissues
copper levels greater than ____ warrant treatment
Iron levels greater than _____ may cause inflammation
2000 ppm
1200 ppm
when treating chronic hepatitis, what is the first type of drug we try?
glucocorticoids for anti-inflammatory effects
When would you want to avoid glucocorticoids
infectious hepatitis
acute hepatitis (will lead to increased mortality)
What specific glucocorticoid is provided for cats (dosage)?
prednisolone 1-2.2 mg/kg/day
tapered to 0.5-1 mg/kg EOD
What liver enzyme should decrease with effective glucocorticoid therapy?
ALT
What glucocorticoid is given to dogs that cannot stand the side effects of pred?
budesonid
For dogs that fail to respond to glucocorticoids, what drug do we procede onto (dose)?
azathioprine 2.2 mg/kg/day for 1 week, followed by 1mg/kg/day EOD for maintenance
Should azothioprine be given to cats who cannot tolerate side effects of prednisolone?
NO
What do you need to make sure to monitor while giving azathioprine?
CBC and liver enzymes
True or false: you should wear gloves while giving azathioprine
True
what does UDA stand for
Ursodeoxycholic acid
true or false: UDA is more hydrophobic than other, more toxic bile acids
false - more hydrophilic
What is the dose used for UDA
15 mg/kg/day or divide
Under what condition is UDA contraindicated?
contraindicated in biliary obstruction
what medication is a microtubule assembly inhibitor and used to slow fibrosis in the liver?
colchicine**
What is the dose for colchicine
0.03mg/kg/day for dogs
What are some drugs thought to decrease fibrosis?
corticosteroids
vitamin E
silymarin
SAMe
Azathioprine
Penicillamine
Zinc
What are some antioxidants that we provide animals with chronic hepatitis?
Vitamin C
Vitamin E*
SAMe*
Silymarin(
zine
N-acetylcysteine
UDA
What is the dose for Vitamin E?
7 IU/kg or 50-400 IU/day
What treatment option is found in normal liver cells and acts as a precursor for cysteine?
SAMe
What is a precursor for SAMe?
methionine
What does cystein help to form - its helpful to reduce oxidative injury
glutathione
What is the dose for SAMe
20 mg/kg/day in dogs
what is N-acetylcystein converted to?
cysteine and glutathione
What are the ways to administer N-acetylcysteine?
orally
IV
How do we dose N-acetylcysteine?
140mg/kg IV followed by 50-70 mg/kg IV for 7 treatments
Oral: 50-70 mg/kg TID - give once any vomiting has stopped
What medication is extracted from fruit of milk thistle
Silymarin
What is silymarin's MOA
increase superoxide dismutase to act against oxidative damage
What is the dose of silymarin?
5mg/kg or 50-250 mg BID
What are the copper chelator medictions and how do they work?
D-penicilamine
2,2,2-tetramine
They bind up free extracellular copper
Which of the copper chelators is first choice?
D-penicillamine
What is the component that binds copper and equesters it in teh gut so it can't be absorbed? What drugs utilize this?
Metallathoinein
zinc gluconate or acetate
When should you give D-penicillamine? Zinc?
D-penicillamine: at feeding
Zind: 1 hour before feeding
True or false: it is alright to give chelators and zinc at the same time
False - chelators bind to zinc
Does zinc address copper that is already present in the liver?
No - only used to prevent further accumulation
What is the main treatment plan for HE?
reduced protein diet
what is prescribed for ascites in animals with chronic hepatitis?
dietary sodium restriction is limited
What type of medications should be used fo GI ulcers?
GI protectants (carafate)
H2 antagonists (famotidine, ranitidine)
PPIs
What type of prognosis do we see with chronic hepatitis?
variable - but dogs with clinical signs show progression and death in weeks to months
What breeds carry a poorer prognosis with chronic hepatitis?
Doberman, cockers, dalmations
Doberman Pinscher - what is the signalment of most affected dogs?
middle-aged females
What type of chronic hepatitis are dobbies prone to?
severe forms, cirrhosis and acute decompensation
Is hemorrhage common in dobies with chronic hepatitis?
yes
What is the prognosis of dobies that get chronic hepatitis?
poor - death often occurs within weeks of diagnosis of symptomatic dogs.
Early diagnosis/therapy has not greatly improved survival times
Bedlington terriers area commonly affected breed - what is the supposed reason frot his?
autosomal-recessive defect in copper transport proteins (higher hepatcellular accumulation, apoptosis, and inflammation)
What are considered normal copper levels? when do they start to cause problems?
<500ppm
>2000 ppm
How do we definitively diagnose copper accumulation?
biopsy
Bedlington have the genetic component to their chronic hepatitis. Explain the copper levels seen in Heterzygotes and homozygous recessive at 6 and 15 months
Heterozygotes:
6 months - higher levels, decrease at 15 months
Homozygous recessive
6 months high, even higher at 15 months
How do we treat copper accumulation?
low copper diets, chelators, and zinc supplementation
How long do we give chelators for?
until copper levels drop to <1000ppm
What do we use for maintenance of copper accumulations
low copper diet, and zinc supplementation
What breed is more commonly affected with increased hepatic copper levels than any other breed?
Westies
true or false: Like other breeds, westies continue to accumulate copper as they age
False - westies stop accumulating copper as they age - actually decreases!
What is the average life span of dalmations that are affected with chronic hepatitis?
80 days - super short!
How do cocker spaniels with chronic hepatitis typically present?
young males, with ascites
What is the life span of an affected cocker spaneil?
most die within a month of presentation
What drugs can cause acute or chronic hepatitis?
technically, any drug because the liver filters so much blood.
The following cause inflammation:
Phenobarbital
TMS
Diethylcarbamazine
osibendale
Amiodarone
Is lobular dissecting hepatitis common?
No - its rare
What is the typical signalment of an animal with lobular dissecting hepatitis?
young dogs
possibly elevated copper levels
What is the Tx/Px of lobular dissecting hepatitis?
Anti-inflammatories, anti-fibrotics, diuretics for ascites, chelators
Prognosis is poor
How is granulomatous hepatitis differentiated from chronic hepatitis?
preponderance of macrophages
What are some organisms that are associated with granulomatous hepatits?
Bacterial: Nocardia, Rhodoccocus, Borrelia, Bartonella, Histoplasma, cocciciodes, Hepatozoonosis, Mycobacterium
Neoplasic: lymphoma
histiocytosis
lymphangectasia
True or false: Many causes of granulomatous hepatitis are idiopathic
True
Do we start treatment of granulomatous hepatitis with immunosuppressive drugs?
No - only used as a last resort (bacterial components possible)