Managing Canine and Feline Liver Disease Flashcards
how are acute hepatopathies treated (3)
- largely supportive (manage c/s, complications, fluids, antioxidants, antiemetics)
- address underlying cause if known (withdrawal/emesis of hepatotoxic drug, doxycycline if leptospirosis)
- steroids not indicated
how are chronic hepatopathies treated (3)
- specific therapy should be based on biopsy (steroids and colchicine should only be administrated after biopsy)
- even without biopsy, non specific therapy is warranted (antioxidants, ursodeoxycholic acid)
- many drugs undergo hepatic metabolism so carefully consider meds
what are hepatoprotection mechanisms
glutathione (GSH) is an antioxidant and free radical scavenger
what is gultathionine synthesized from
its synthesized from cysteine, glutamate, and glycine
what do decreased GSH indicate
severe liver disease
what are commonly used nutraceuticals used in liver disease (4)
- antioxidants: s-adenosylmethionine (SAMe)
- vitamin E
- silybin
- zinc
what is s-adenosylmethionine (SAMe)
precursor of GSH
what effects does s-adenosylmethionine (SAMe) have
anti-inflammatory and antioxidant effects
when is s-adenosylmethionine (SAMe) used
acute toxic hepatopathies
adjunctive treatment in inflammatory disease, cholestatic hepatopathies
what are the side effects of s-adenosylmethionine (SAMe)
low incidence of side effects
- nausea
- GI signs
what does of s-adenosylmethionine (SAMe) is used
20 mg/kg/day PO
what is silymarin
derived from milk thistle plant
what effects does silymarin have
anti-fibrotic
anti inflammatory
anti oxidant
when is silymarin used
mushroom toxicity (amanita phalloides)
what are the funcitons of vitamin E
protect phospholipids membrane from oxidative damage when free radicals are formed
is there a benefit of vitamin E in liver disease
unclear
increase in GSH, but no improvement in clinical or histological findings
what are the functions of n-acetylcysteine (NAC)
pro drug of cysteine that helps replenish hepatic intracellular cysteine and GSH concentrations
when is n-acetylcysteine (NAC) used
in acute liver injury due from drugs/toxins
how does n-acetylcysteine (NAC) help with paracetamol toxicity in cats
toxic intermediate (NAPQI) is formed in cats which is detoxified by conjugation to glutathione
cats are deficient in the glucuronidation pathway or if GSH reserves inadequate with toxic dosage
NAPQI can cause hepatic and RBC injury
cysteine is needed for glutathione production
what is ursodeoxycholic acid (UDA)
synthetic hydrophilic bile acid
what is the function of ursodeoxycholic acid (UDA) (3)
- may displace toxic hydrophibic bile acids
- increases glutathione production in hepatocytes
- promotes bile flow
when is ursodeoxycholic acid (UDA) contraindicated
contraindicated in biliary obstruction because it promotes bile flow
what are the uses of ursodeoxycholic acid (UDA) (2)
- medical management of GB mucocele
- acute and chronic hepatopathies –> particularly where cholestasis plays a role
what is vitamin K required for
hepatic synthesis of II, VII, IX, X
what is the dosage of vitamin K
2.5 mg - 5 mg/kg SC or PO
IV admin risk of anaphylaxis
how should vitamin K be administrated in biliary disease or anorexia
fat soluble vitamins are not absorbed
so need to give vitamin K SC
when are antibiotics in liver disease indicated
when bacterial infection is primary or secondary complication and in treatment of hepatic encephalopathy
why should tetracycline, sulphonamides, erythromycin not be used in liver disease
because they are metabolized in the liver
how does hepatic fibrosis occur
with chronic hepatic inflammation myofibroblasts are activated which cause fibrosis
how does fibrosis lead to portal hypertension
collagen impedes blood flow
what does bridging fibrosis lead to
causes permanent hepatic distortion and as fibrosis advances it leads to cirrhosis (end stage liver failure)
what are anti-fibrotic drugs (5)
- prednisolone
- penicillamine
- vitamin E
- SAMe
- silibyn
what is the most common steroid used in chronic hepatitis
prednisolone
what are the effects of prednisolone (4)
- anti-inflammatory
- immunomodulatory effects
- anti fibrotics
- choleretic effects (increase volume of secretion of bile from liver)
what is the ideal dosage and duration for chronic hepatitis
1-2 mg/kg PO q24, gradually taper
look at liver enzymes and evaluate
ideally want to repeat biopsy but often owners don’t want to put dog through it again
what are the indications of steroids in hepatic disease (5)
- biopsy evidence of ongoing inflammation
- infection has been ruled out
- lymphocytic cholangitis (cats)
- chronic hepatitis (dogs)
- no or only early mild fibrosis associated with inflammatory infiltrate
what are the contraindications of steroids in hepatic disease (5)
- hepatic encephalopathy (will cause protein breakdown)
- known or suspected infection
- if portal hypertension, gastric ulceration or ascites (will make worse)
- advanced, bridging fibrosis or non inflammatory fibrosis (suggesting a risk of portal hypertension)
- acute hepatopathy
what effect do steroids have on hepatic enzymes
they can increase
increase in ALP
+/- ALT/AST
if steroids are being given how should you monitor to find the correct dosage for the individual
monitor for signs of glucocorticoid excess
polyuria, polydipsia, polyphagia, alopecia, lethargy, hepatomegaly
what is primary copper toxicosis
defect in biliary copper excretion
progressive accumulation results in chronic hepatitis
what is secondary copper deposition in chronic liver disease caused by
cholestasis causes a defect in copper excretion through the bile
how can a biopsy differentiate between primary and secondary copper storage disease
primary: copper accumulation is in zone 3 (centrilobular)
secondary: copper accumulation in zone 1 (periportal parenchyma)
how is copper storage disease diagnosed
the magnitude of increase of liver enzymes and diagnostic imaging are very similar then dogs with chronic hepatitis
so biopsy is needed
how is copper storage disease treated (4)
- D-penacillamine
- trientine (2,2,2-tetramine)
- dietary management low copper diet with added zinc
- oral zinc
what is D-penacillamine
chelating agent that binds copper and excretes it via the kidneys
what other effects does D-penacilliamine have
immunomodulatory and anti fibrotic properties
what is trientine
chelating agent of copper
used when D-penacillamine causes GI side effects
how does zinc help in copper storage disease
produces metallothionein in intestinal mucosa which prevents uptake into the circulation
which binds copper in the diet
how is leptosirosis treated
barrier nursing
supportive care for different organ systems
antibiotics: doxycycline 10mg/kg PO 2 weeks, penicillin derivative IV if cannot tolerate doxycycline
what is portal hypertension
increases in blood pressure within the portal venous system
what is the relationship between portal blood flow, intrahepatic venous resistance and portal vein pressure
portal vein pressure = portal blood flow x intrahepatic venous resistance
what are the consequences of portal hypertension (4)
- ascites
- GI ulceration
- multiple acquired shunts
- hepatic encephalopathy
how is ascites treated
diuretics
what type of diuretic is spironolactone
aldosterone receptor antagonist –> decreases Na and water absorption from the kidneys so it they are excreted into the urine
conserves K+
what type of diuretic is furosemide
loop diuretic
inhibits luminal Na/K/Cl cotransporter
causes loss of Na/K/Cl so you need to monitor them and make sure you don’t dehydrate the aptient (monitor electrolytes, urea and creatinine)
what are the benefits of an abdominocentesis
comfort and improves respiration
what are the risks of abdominocentesis
hypoalbuminemia, hypovolemia
promote dehydration
what does portal hypertension increase the risk of in the GI tract
ulceration
what can GI hemorrhage result in with hepatobillary disease
hepatic encephalopathy
what is hepatic encephalopathy
neurological abnormalities that may occur with liver dysfunction
accumuluation of toxins (ammonia) leads to altered neurotransmission in the brain
what is hepatic encephalopathy associated with
portosystemic shunt
cirrrhosis
acute fulminant hepatic failure
what are the clinical signs of hepatic encephalopathy (8)
- lethargy
- head pressing
- blindness
- seizure
- abnormal behaviour
- ptyalism (cats)
- ataxia
- coma
how is hepatic encephalopathy treated (6)
aim is to reduce ammonia
- diet
- antibiotics
- lactulose
- fluid therapy
- gastro protective medication
- siezure medication
how can the diet manage hepatic encephalopathy
small frequent meals
protein restriction –> minimize demand on urea cycle
what diet changes can be made in young animals to treat hepatic encephalopathy
can’t restric protein completely
will break down endogenous protein
so feed as much protein as can be tolerated (hepatic prescription diets, add tofu, low fat cottage cheese, no red meat)
purina HA a soya based may be better
what antibiotics are used to treat hepatic encephalopathy (4)
- ampicillin
- neomycin
- metronidazole (low dose 7.5 mg/kg BID)
- amoxicillin and clavulanic acid
what is the purpose of using antibiotics to treat hepatic encephalopathy
to decrease GI ammonia producing bacteria
why is lactulose used to treat hepatic encephalopathy
soluble fibre that acidifies colonic contents which will reduce ammonia absorption and also increase colonic bacterial cell growth which will incorperate ammonia into their cell walls
it also decreases intestinal transit time so there are less opportunities to absorb ammonia
why should hartmann’s be avoided as a fluid therapy in hepatic encephalopathy
because it contains lactate
what is the fluid of choice for hepatic encephalopathy
0.9% NaCl
supplement with maintainence KCl
add glucose to fluids if low (liver makes glucose)
how can the seizures caused by hepatic encephalopathy be managed
dizepam or midazolam for immediate control
levetiracetam is preferable
propofol CRI
what are portosystemic shunts
vascular anomalies that redirect blood from the portal vein to the systemic circulation bypassing the hepatic sinusoids and liver parenchyma
how does portosystemic shunting lead to hepatic encephalopathy
toxins, proteins and nutrients are absorbed by the intestines enter the circulation
what are the types of portosystemic shunts
congenital or acquired with portal hypertension
how do congenital portosystemic shunts occur
fetal liver has large shunting vessels (ductus venosus) to byoass the hepatic circulation which should normally close at birth
what are the types of macroscopic congenital portosystemic shunts
- extrahepatic
- intrahepatic
what breeds are susceptible to congenital extrahepatic shunts
smaller dogs
yorkies, matlese
what breeds of dogs are more susceptible to intrahepatic shunts
larger dogs
labs
what are microscopic congenital portosystemic shunts
portal vein hypoplasia (also known as microvascular dysplasia)
what are the clinical signs of congenital portosystemic shunts (5)
- neurological signs: hepatic encephalopathy, seizuring
- urinary (PUPD, urate urinary stones)
- GI (vomiting, diarrhea)
- failure to thrive, poor coat, “runt” of liver
- copper irises (cats only)
how are congenital portosystemic shunts diagnosed (4)
- increase in bile acids, ammonia
- decrease in urea, albumin
- ultrasound (consider referral)
- biopsy liver if no macroscopic shunt on imaging
how is congenital PSS treated
- medical: stabilize HE (diet, lactulose, antibiotics)
- surgery (treatment of choice)
- long term medical management if surgery not feasible
how does an aquired portosystemic shunt occur
develop from opening of embyronic vessels
compensatory mechanism to chronic portal hypertension
how are acquired shunts treated
medically managed
cannot be ligated
describe the general contents of liver diets (3)
- restricted in protein
- low in copper, high in zinc
- vitamins B and E, antioxidants
what are the indications for a liver diet (2)
- hepatic encephalopathy
- copper storage disease
when are liver diets not indicated
- acute hepatopathies
- ascites
- if you don’t know, but the liver enzymes are up
what is hepatic lipidosis
cholestatic liver disorder
what is hepatic lipidosis caused by
negative energy balance caused by anorexia leads to enhanced mobilization of fat stores in the liver
abnormal accumulation of lipids in the hepatocytes –> severe intrahepatic cholestasis, hepatic dysfunction
what is the signalment of hepatic lipidosis
typically middle aged overweight cats
what are predisposing factors to hepatic lipidosis (3)
- obesity
- anorexia
- stress
what can hepatic lipidosis be secondary to (4)
- pancreatitis
- cholangitis
- IBD
- neoplasia
- obesity, prolonged anorexia and stress
what will be seen on biochem with hepatic lipidosis
increase in ALP
normal GGT
what will the liver appearnce be on US with hepatic lipidosis
hyperechoic hepatic parenchyma and hepatomegaly
how is hepatic lipidosis treated (6)
- IV therapy
- treat underlying causes
- feed the cat ASAP
- mintor glucose and electrolytes (esp K+ and PO43-)
- vitamin K
- supportive treatment (anti emetics, anti oxidants, pain relief)
what type of diet should you feed a cat presenting with hepatic lipidosis
feeding tube if needed
high quality diet, high protein (+/- taurine, B vitamins)
gradually delivery –> day 1 33% RER, day 2 66% RER, day 3 100%
