Hepatic Encephalopathy Flashcards
dogs and cats, most frequent cause of HE:
up to ___% of affected animals demonstrate neurologic clinical signs
communications are generally:
congenital extrahepatic or intrahepatic portal-to-systemic venous communications
up to 95%
single vessel, but multiple extrahepatic/ntrahepatic can occur
Hepatic arteriovenous malformations cause:
young dogs, ddx:
older animals, ddx:
Cats:
portal hypertension
multiple extrahepatic PSS
and ascites
hepatic microvascular dysplasia
rarely, congenital urea cycle deficiencies
PSS secondary to PH secondary to liver dz
hepatic lipidosis
pathophysiology of HE is complex
recent work has reemphasized the importance of elevated ______
other substances considered synergistic to ammonia toxicity include:
ammonia
mercaptans, free fatty acids, phenols, bile salts
ammonia is produced in the GI by:
then it is absorbed into the:
and rapidly converted to:
in the:
PSS or significant liver disease =
BBB permeability to ammonia increases in HE
how does ammonia decrease excitatory NT in the brain:
- bacT breakdown of a.a., purine
- enterocyte metabolism of glutamine
- bacT breakdown of urea by urease
portal blood
urea or glutamine
liver
high levels of ammonia are present in the systemic circulation
down-regulating the N-methyl-D-aspartate (NMDA, excitatory) receptors
and blocking Cl extrusion from the postsynaptic neuron, decreasing inhibitory neurotransmission
brain has no urea cycle; consequently, ammonia in the CNS is removed by:
transamination of glutamate into glutamine in astrocytes
glutamine concentrations in the cerebrospinal fluid are elevated in dogs with HE and correlated w.:
Glutamine is exchanged across the blood-brain barrier for ______
tryptophan metabolites:
serotonin NT is…
quinolinate NT is…
glutamine also is transported from astrocytes into neurons, where it is:
overstimulation of the NMDA receptors by:
can cause seizures and neurotoxicity, in part because of:
degree of neuro dysfunct in humans w HE
tryptophan & tryptophan metabolites in CNS
serotonin & quinolinate
inhibitory neurotransmission
excitatory neurotransmission
converted back into glutamate
glutamate and ammonia
free radical formation
inhibitory NT:
several different observations implicating “increased GABAergic tone” in HE…
if increased GABA neurotransmission exists in patients with HE, it is due to increased:
what increases the expression of “peripheral-type” benzodiazepine receptors (PTBR) (a heterooligomeric protein complex on the outer mitochondrial membrane of astrocytes):
activation of the PTBR increases mitochondrial cholesterol uptake and synthesis of:
GABA
increased GABA have NOT been found in HE
not GABA itself but…
endogenous GABA ligands:
endogenous benzodiazepines & neurosteroids
ammonia & manganese (also seen in liver disease)
neurosteroids - act on GABA receptors
Microglial cell activation =
tx w. N-acetylcysteine and minocycline has been shown to ameliorate CNS inflammation and brain edema in experimental studies
a.a imbalances may play a role in HE
decreased ratio of:
increase in aromatic amino acids
leads to an increased synthesis of:
Normal dogs infused with the aromatic amino acids tryptophan and phenylalanine became:
production of proinflammatory cytokines (TNF-α, IL-1β) - occurs early in HE
branched-chain (valine, leucine, isoleucine): to aromatic (phenylalanine, tyrosine, tryptophan) amino acids
false NT
reduction in synth of dopamine & NE
comatose
addition of branched chain amino acids to the infusion prevented coma
CS
depression, dementia, stupor, coma, muscle tremors, motor abnormalities, excessive salivation, and focal or generalized seizures
cat CS
dogs PU/PD MoA:
ptyalism is common, and is often only CS
- secondary to hypercortisolemia
cortisol inhibits AHD - ineffective medullary concentrating bc low urea levels
what precipitates CS:
drugs:
high protein meal GI bleeding systemic infection hypoNa, hypoK hypoglycemia acidosis & alkalosis constipation
narcotics and other anesthetic agents
Diagnosis
dx or exclusion:
liver function tests:
samples for blood ammonia concentrations are useful only if processed:
rectal portal scintigraphy
liver histopathology
CS + PSS or liver dz
toxin or drug ingestion, intracranial lesions
blood ammonia levels
pre- and postprandial bile acids
sulfobromophthalein (BSP) dye retention
immediately
Tx - Seizures:
use of diazepam is controversial because:
can still try and dose
alternatively, the seizure activity may be treated with:
If cerebral edema
AED an attempt to prevent further seizures:
difficulty is:
possibility of > levels of endogenous benzos
propofol (0.5 to 1 mg kg IV bolus, then 0.05 to 0.1 mg/kg/min CRI) although careful respiratory monitoring is essential
Mannitol
KBr is given commonly
Phenobarbital 16 mg/kg IV divided into four doses given on day 1
2 to 4 mg/kg IV q12h
bromide & PB may lead to excessive sedation .:. close monitoring is essential
predisposing factors tx:
i.e.if sedated w benzo.
intubation of comatose animals
alkalosis causes
hypokalemia causes
Colloid administration (synthetic or natural/plasma), and potassium and glucose supplementation are often necessary
reverse w. flumazenil (0.02 mg/kg IV)
protect the airway from aspiration and ensure adequate ventilation.\
increases ammonia diffusion into CNS
stimulates renal ammonia production
if need RBC what do you use?
FWB or fresh pRBC
bc blood storage increases ammonia
lactulose enema:
lactulose (beta galactosidofructose) is a:
1 to 3 ml/10 kg diluted 1 : 1 to 1 : 3 w warm H2O
-minimize ammonia production and absorption
nonabsorbable disaccharide
osmotic cathartic
intestinal bacT hydrolyze lactulose-producing-
-organic acids
-lower colonic pH
-acidification traps ammonia in its NH4+
-preventing absorption by nonionic diffusion and also resulting in the net movement of ammonia from the blood into the bowel lumen.
Fulminant hepatic failure (FHF) is
death in humans w FHF often associated w:
assisted MV why?
mannitol, dextrose, FFP, Ab
uncommon
cerebral edema, hemorrhage, and sepsis
prevent hypo- or hyperventilation and minimize changes in intracranial pressure
Tx goals:
CS of HE typically can be managed w:
diet:
protein source:
reducing ammonia levels
decreasing GABA
lowering endogenous benzodiazepines
diet modification
oral administration of lactulose
antimicrobial therapy
moderately protein restricted (14% to 17% protein on a dry matter basis in dogs; 30% to 35% protein in cats) and high in CHO
high-quality protein w increased BCAA
branched-chain amino acids
low-residue, easily digestible food to minimize the amount of material reaching the colon
Cats, essential a.a necessary for urea:
arginine
Lactulose (1 to 3 ml/10 kg BW diluted 1 : 1 to 1 : 3 with warm water q6-8h) is administered orally or rectally, and the dose rate and interval are titrated to:
2-4 moderately soft stools daily
Ab 3.
Neomycin sulfate (20 mg/kg PO q6-8h) generally is considered nonabsorbable but should be avoided in animals with concurrent renal disease
Metronidazole (7 to 10 mg/kg PO or IV q12h) is a reasonable alternative, but neurotoxicity may occur more commonly in animals with hepatic disease.
Rifaximin is an oral antimicrobial recently approved for the treatment of humans with hepatic encephalopathy.
benefit of combined lactulose and antimicrobial therapy is open to question
therapeutic effect of lactulose depends in part on its metabolism by colonic bacteria,
Although the two treatments often are considered synergistic, oral neomycin inhibits lactulose metabolism in 25% to 30% of human patients
liver insufficiency commonly experience gastrointestinal hemorrhage and the digested blood serves as a protein source
recommended that these animals receive gastrointestinal protectant therapy
