Liver Failure Flashcards
How is acute liver failure defined in people?
- decreaed liver function
- coagulopathy
- no preexisting liver disease
- signs consistent with HE
List 4 functions of the liver
- carbohydrate, fat, protein metabolism
- metabolism and detoxification
- bile production
- coagulation factor production + other proteins
What part of the hepatic lobule is most sensitive to toxins and why?
central vein - because lowest O2 cc and highest cytochrome P-450 (i.e., more toxic metabolites accumulate here)
How does ammonia lead to cerebral edema?
enters astrocytes
together with glutamate –> forms glutamine –> osmotically active
also inserts aquaporine-4 channels - enhances this water movement intracellularly
How is the coagulation system affected by liver failure (4 points)
- less procoagulation factor
- less anticoagulant factors
- derangements of fibrinolysis
- less and dysfunctional platelets
What is the most common sign of hepatic encephalopathy in cats?
ptyalism
List 9 precipitating factors of hepatic encephalopathy
- hypokalemia
- hyponatremia
- GI bleed
- constipation
- renal disease/azotemia
- high protein meal/diet change or indiscretion
- sepsis/SIRS
- furosemide administration
- alkalosis
What are the grades for hepatic encephalopathy?
0 - normal
1 - mild impairment or apathy
2 - severe apathy, mild ataxia
3 - severe ataxia, head pressing, circling etc.
4 - seizures, stupor/coma
Explain how acetaminophen causes liver toxicity
acetaminophen –> oxidized by cytochrome P-450 –> NAPQI –> free radical, i.e., cytotoxic (destroys cell membranes, including liver and RBC especially)
zone 3 centrilobular hepatocellular necrosis
NAPQI can be detoxified by conjugation with glutathione –> when depleted –> cell damage
What is the mechanism of toxicity of aflatoxin-induced liver failure?
aflatoxin B1
DNA-polymerase inhibition –> cells cannot produce needed proteins and die
What are the 3 phases of amanita mushroom toxicity?
GI phase
latent phase
hepatorenal phase
What is the mechanism of action of sago palm toxicity?
cycasin toxin
toxic compund of cycasin decreases mitochondrial ATP activity and glucose-6-phosphatase –> centrilobular and midzonal coagulation necrosis and hepatocellular death
How soon after exposure to oral diazepam can cats develop hepatic necrosis?
5-13 days
How is leptospirosis thought to induce hepatotoxicity?
indirectly through cholestasis of sepsis
What type of crystals occur in dogs with PSS?
urate crystals, ammonium-biurate
What are the recommended antibiotics to reduce ammonia load in PSS/HE?
- Ampicillin
- metronidazole
What is cimetidine and how does it work?
cytochrome P-450 inhibitor - will reduce load of toxic metabolite (NAPQI) from acetaminophen, has to be given within 16 hours of exposure
What is the primary toxin in sago palm, and what part of the plant is it most concentrated in?
cycasin
seeds
What is the toxin in Cyanobacteria?
blue green algae
microcystins
What is the treatment for Amanita mushroom toxicity?
Silamaryn
Penicillin G
How is xylitol suspected to cause hepatotoxicity?
ATP depletion leading to hepatocellular necrosis
oxidative injury from ROS production
What are the 3 main serovar causing leptospirosis disease in dogs?
gryppothyphosa
pomona
icterohemorrhagica
A single leptospirosis titer > ________ in an unvaccinated dog with classical clinical signs provides a presumptive diagnosis
1.800
A ______-fold increase in paired leptospirosis titer is consistent with a previous infection
4-fold
