Hepatobiliary Flashcards
Define hepatic encephalopathy
spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of other known brain diseases
What are the classifications used by people and vets for HE
A: acute liver failure in the absence of pre-existing liver disease
B: associated with portal systemic bypass
C: associated with cirrhosis and portal hypertension
What are the subcategories of veterinary HE
0- None
1 - Mild decrease mobility, apathy, or both
2- severe apathy, ataxia, or both
3- hypersalivation, severe ataxia, head pressing, blindness, circling
4. seizures, stupor, coma
How is ammonia handled in the liver
Net Loss- ammonia detoxification
1) Urea cycle- converts NH3 to urea: Low affinity but high capacity, occurs during alkalosis
2) Glutamine production: High affinity, low capacity occurs during acidosis
How is ammonia handled in the intestines
Net gain
Microgranisms break down urea to produce ammonia
Enterocytes breakdown glutamine to make glutamate and NH3
How is ammonia handled in the skeletal muscle
Sink
Glutamine production
How is ammonia handled in the cerebrum
Glutamine made in astrocytes, broken down in the neurons
NH3 freely crosses BBB
What role to astrocytes place in HE
Glutamine re-enters astrocyte and metabolized back to NH3 leads to mitochondrial damage, ROS and osmotic swelling
Glutamate release cuases aggitation confusion and seizures
What are the contributors to HE development
Aromatic amino acids, altered neuroreceptors Bile acids, endogenous benzodiazipines False neurotransmitters Mercaptans- toxic metabolits Gaba, Glutamine
What are common underlying causes of HE in veterinary patients and their class
Conginetal PSS (B) Developemnt of PSS (c) ALF (A) Congenital urea recycling disorders- dogs Arginine deficiency in Hepatic lipidosis
What are 10 precipitating factors for HE development
High protein diet. GI hemorrhage, Hypokalemia, azotemia/dehydration, alkalosis, diuretic admin, blood transfusion, sedative use, SIRS/Sepsis, arginine deficiency in cats
How does ammonia play in the diagnosis of HE
Fasting concentrations rarely predict severity. Not run in people. But still recommended vet.
Sample handling important EDTA/Lithium heparin tube
run in 30 minuts
RBCs can release NH3 ex vivo
What is the number one goal of treatment for HE
Treat underlying cause of HE
When should enemas be given with HE
if constipated, or if severely neurologically affected
Warm water as good as lactulose
What are the diet recommendations for HE
Dogs: Protein limited
Cats: need protein especially with hepatic lipidosis
Which anticonvulsants are recommended for HE
Levetiractam,- renally excreted
Pheno okay for short term shown to control seizures with CPSS; get profound sedation
Why are benzodiazepines not recommended for HE
Liver metabolize, Can get ALF in oral admin to cats
May cause excessive sedation
How is albumin production by the liver increased
decreased COP, Adquate nutrition increase
Carbs, and increased COP decrease production
What is the net charge of albumin and the half life
66Kda
Negative
D 7-10 days, C 6-9 days
How does total plasma protien indicate hypoalbumenima and hypoprotienemia
< 5.8 g/dl strongly indicates hypoalbum and hypoprotienemia
What can falsely increase total plasma protien measurements by refractometer
hyperglycemia and hypercholesteremia
Define acute liver injury
acute hepatocellular damage and necrosis with retained hepatic function
Define acute liver failure
occurs once hepatocelluar damage is so extensive that it compromise hepatic synthetic, excretory and regulatory functions
What are the three criteria for ALF in people
absence of pre-existing disease
HE within 8 weeks of increase bilirubin
coagulopathy
What are the two mechanism for toxin injury in ALF
Direct (destructive): not selective damage
Indirect (disruptive): selective disruption of cell function or structure
What is the mechanism of injury of ALF for Sago palms
Cyasin leads to hepatocellular necrosis- direct
48-72 hours
Increase Tbili has decrease prognosis
What is the mechanism of injury of ALF for blue-green algea
Microcystins disrupt hepatocyte cytoskeletin leading to necrosis– indirect
What is the mechanism of injury of ALF for amanita
Cells contact with toxin have rapid rate of turn over
Direct
What is the mechanism of injury of ALF for aflatoxins
Acute: metabolites cause direct damage to liver oxidative damage due to depletion of intracellular glutathione
Chronic: Immunodeficiency and hepatic neoplasia
Measure Aflatoxin B in urine up to 48 hrs after ingestion
What is the mechanism of injury of ALF for xylitol
Mild self limiting dose dependent increase in hepatic transaminase activity
Idiosyncratic - ATP depeletion leading to hepatocellular necrosis and ROS
What is the mechanism of injury of ALF carprofen
Idiosyncratic
What are the mechanisms of ALF associated with drugs
Intrinsic- dose dependent, predictable
Idiosyncratic- non dose dependent; often due to a production/acclumation of a toxic metabolite or immune response to parent drug/ metabolite
What is the mechanism of injury of ALF with acetaminophen
Direct intrinsic hepatotoxin
Tx replace glutathione stores with NAC/SAMe
What is the mechanism of injury of ALF with phenazyopyradine
produces acetominophen as metabolite which induces toxicosis
Direct intrinsic hepatotoxin
What is the mechanism of injury of ALF with sulfonamides
Idiosyncratic necrosis
What is the mechanism of injury of ALF with zonisamdie
Idiosyncratic necrosis
What is the mechanism of injury of ALF with leptospirosis
Unknown—necrosis
Bilirubin peaks 6-8 days after onset and though to correpsond to necrosis
ALKP increased larger than ALT
Transmitted through urine up to 7 days previous
What is the mechanism of injury of ALF with canine adenovirus
Young, oronasal transmision
acute hepatic necrosis
What is the mechanism of injury of ALF with hepatic lipidosis in cats
> 50% of hepatocytes have lipid vacoules
What is the mechanism of injury of ALF with platynosomum fastosum in cats
Flukes invade/obstruct biliary ducts and gall bladder after cats ingest lizard
What is the mechanism of injury of ALF with stanozol in cats
anabolic steroid, ALI then get ALF
What is the mechanism of injury of ALF with oral benzodiazepines in cats
Idiosyncratic
What is the mechanism for increased bilirubin in ALF
Cholestatsis
Leakage from tight junctions
Swelling of hepatocytes obstruct flow
Necrosis of hepatocytes
What is the mechanism for coagulaopathies in ALF
Thrombocytopenai, functional Vit. K deficiency, Dysfribrionogenemia, hyperfibrinolysis, and clot promotion
Can bleed or form thrombi
How does thrombcyopenias occur in ALF
Decreased heaptic production of thrombopoetin
Over stimulation of primary hemostasis by continous low grade activiation of the endotheial cells
Increase platelet consumption due to hemorrhage
What causes the functional Vit. K deficiency in ALF
Decreased bile flow altering absorption
decreased intake due to anorexia
decreased bacterial production of Vit K in gut
Most common in cholestatic disease
What leads to hyperfibrinolysis in ALF
decreased clearance of plasminogen activators by failing liver
What promotes clotting/thrombis in ALF
increased vWF, Factor VIII, decreased Protien C, Protein S and antithrombin
How doe transaminases increase in liver injury
Stored in hepatocytes released with membrane damage
Elevation does not correlate with hepatocellular damage
Mycrocytins and aflatoxins inhibit so increase does not occur
What does a decrease ALT mean with ALF
recovery
severe hepatocellular damage that hepatocytes no longer able to make ALT
What electrolyte abnormalities are noted with ALF
Hypokalemia Hypophosphatemia Hyperphosphatemia
Hyponatremia
Increased lactate
Metabolic acidosis
What are the theorized mechanisms of gall bladder mucoceles
Gall bladder dysmotility
Decreased bile flow or stasis
altered bile compisition
In which dogs are GBM more likely to occur
older dogs
shetland sheep dogs, min schnauzers, cockers
Hyperadrenocorticism, hypothyroidism, and hyperlipidemia
What is the lethal triad that leads to a poor prognosis
acidosis, hypothermia lead to metabolic acidosis
What is bile composed of
Water, mucin, conjugated bile acids, bile pigments, cholesterol, phospholipids, inorganic alts
What is NAC
N-acetylcystine
Sulfhydryl donation; thiol precurosor of L-cystine and reduced glutathione
Across all studies culturing bile what is the most common two bacteria cultures
E. Coli, Enterococcus
What is the dominate form of ammonia in the blood?
NH4+; ammonium ion
