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
What are the best samples for leptospirosis antigen detection and what are their time frames for sampling?
first 10 days - blood
after 10 days - urine - carrier stage
What are the recommended treatments for the active infection versus carrier stage for leptospirosis in dogs?
active infection - ampicillin/sulbactam
carrier stage - doxycycline
How does acute liver failure cause high bilirubin
- intrahepatic cholestasis from:
- leakage of tight junctions that separate bile canaliculi from blood
- hepatocyte swelling - bile canalicular flow obstructed
- necrosis of hepatocytes
What are the 3 main causes of thrombocytopenia in acute liver failure?
- less thrombopoietin production
- blood loss
- consumption - primary hemostasis activation
Why are patients with acute liver failure hyperfibrinolytic?
decreased tPA and uPA clearance by the liver –> accumulate in blood and increase fibrinolysis
What are the 3 types of hepatic encephalopathy?
A - from acute liver failure
B - PSS
C - chronic liver disease and cirrhosis
Where in the cell are ALT and AST found?
ALT - cytoplasm
AST - cytoplasm and mitochondria
How does hypokalemia precipitate hepatic encephalopathy?
increases renal ammoniagenesis
less potassium –> leads to K absorption in exchange for H+ secretion –> more acidic intraluminal environment –> enhances ammonia absorption
Is hypophosphatemia or hyperphosphatemia a negative prognostic indicator in acute liver failure?
hyperphosphatemia
hypophosphatemia develops from increased cell regeneration - good sign
How do arterial and venous ammonia concentrations compare?
similar in healthy individual
arterial higher in patients with HE
Why is vasopressin not recommended in patients with acute liver failure?
causes cerebral vasodilation –> inceases ICP
