Hepatic Encephalopathy Flashcards
List 8 factors other than ammonia, implicated in the pathogenesis of HE
- glutamate
- GABA
- aromatic amino acids
- manganese
- endogenous benzos
- endogenous opioids
- mercaptans
- tryptophan-serotonin system alterations
Describe the two different types of brain edema. What type is present in HE and which type indicates steroid administration?
cytotoxic - fluid shifts into the cell, e.g., from increased osmotic pull
vasogenic - inflammation and endothelial damage leding to fluid leakage from vasculature (increased vascular permeability)
HE - cytotoxic - glutamine causing osmotic pull (i.e., characterized by abnormal intracellular fluid shift)
Why do cats with hepatic lipidosis sometimes develop hyperammonemia? (even in the face of normal hepatic function)
arginine deficiency from anorexia
necessary for the urea cycle
What is the chemical formula of ammonia versus ammonium?
NH3, NH4
Describe the production of ammonia and ammonium in the GI tract and how they’re absorbed
produced mostly by urease-producing bacteria from dietary protein
ammonia can be freely absored through cell membrane
ammonium cannot pass cell membranes
What are the 2 processes by which ammonia is metabolized?
ornithin/urease cycle –> convert ammonia to urea (in the liver, periportal hepatocytes)
transamination –> adds ammonia to glutamate (amination) –> producing glutamine (in the pervenous hepatocytes, brain, skeletal muscles)
Describe how ammonia leads to cerebral edema and neurologic injuries
enters astrocytes
binds with glutamate –> forms glutamine –> water pull (osmotically active) –> cytotoxic edema
ammonia also inhibits glutamine release from astrocytes
aquaporine-4 channels inserted into astrocyte’s cell membranes
then glutamine will undergo deamination –> releases glutamate and ammonia –> ROS and RNOS produced –> further cell damage
ammonia may increase BBB permeability
What is the mechanism of action by which lactulose helps reduce ammonia levels?
converts NH3 to NH4+ –> trapped in GI tract
osmotic cathartic - faster GI transit time, less time for ammonia absorption
Lactulose, a non-absorbable disaccharide, decreases ammonia production and absorption in the colon by decreasing colonic pH, causing a shift from ammonia to ammonium, with the latter being poorly absorbed by the gastrointestinal mucosa. It also decreases gastrointestinal transit time and inhibits glutaminase activity, decreasing intestinal uptake of glutamine and its metabolism to ammonia
What type of bacteria produce ammonia?
urease-forming bacteria
List 10 confounding factors worsening/precipitating HE
- hypokalemia
- hyponatremia
- hypoglycemia
- protein-rich meal
- constipaiton
- metabolic alkalosis
- GI bleeding
- dehydration
- renal disease
- diuretic administration
How does hypokalemia increase the risk for HE?
- increases renal ammoniagenesis (ammonia production)
- promotes metabolic alkalosis –> increaes ration of NH3:NH4+
Explain why PSS should be ligated/occluded slowly
because of risk of forming iatrogenic prehepatic portal hypertension
what are the two available devices for delayed PSS occlusion?
ameroid constrictor
cellophane band
What is the current evidence for preemptive anti-seizure drug therapy before shunt occlusion surgery?
conflicting, most recent recommend starting levetiracetam early/before surgery
How late after shunt attenuation surgery can neurologic complications occur in dogs or cats?
72 hours dog
5 days cat
Why is potassium bromide avoided in cats?
induces lower airway disease
What are the 3 types of hepatic encephalopathy?
A. Acute liver failure - absence of preexisting liver disease
B. PSS - without intrinsic liver disease
C. liver cirrhosis, portal hypertension, or acquired PSS
What are the 2 enteric sources of ammonia?
- urease producing bacteria
- glutaminase activity in enterocytes
Do the kidneys produce or metabolize ammonia?
can do both
glutamine synthase and glutaminase present
Why can loss of skeletal mass predispose to HE?
skeletal muscles have glutamine synthase –> can act as an ammonia sink
How can ammonia affect the immune-system?
- inhibits phagocytic acitivty
- inhibits neutrophil chemotaxis
- causes oxidative burst
Which types of HE are most common in SA?
1st Congenital PSS (Class B)
2nd Acquired PCC (Class C)
Class A not common
What is the treatment of choice for intra- versus extrahepatic PSS?
extrahepatic:
* ameroid ring
* cellophane band
intrahepatic
* transjugular embolization
aquired - closure contraindicated –> would result in acute exacerbation of portal hypertension
What was found in the study by Serrano et al, on CPSS treatment with lactulose, diet, metronidazole in dogs?
diet + lactulose superior to diet alone, or diet + metronidazole
adding metro to diet + lactulose did not improve clinical scores
What was found by Carrera et al.’s study on outcome of dogs with post-attenuation seizures after surgical correction of PSS
- 60% of dogs developed post-attenuation seizures
- 40% had neurologic signs other than seizures
of those:
48% signs resolved by discharge
the ones with persisting sings - 70% resolved at home
50% of dogs that had post-attenuation seizures had seizure reoccurence
Os graded high WOL
90% survived > 6 months if they survive at least 30 days
