Hepatic Encephalopathy. JVECC Flashcards
What are the most common causes of hepatic encephalopathy in dogs versus cats?
Dogs
* congenital PSS
* acquired PSS from portal hypertension
Cats:
* congenital PSS
* arginine deficiency from hepatic lipidosis
What are the three types of hepatic encephalopathy?
Type A: from acute liver failure
Type B: from abnormal portal circulation - without haptocellular disease (e.g. congenital PSS)
Type C: cirrhosis, portal hypertension, or acquired PSS
What is covert hepatic encephalopathy?
patient with no neurologic signs but abnormal psychometric tests results (also called minimal HE)
Compare ammonia and ammonium
Ammonium NH4+
* no lipid soluble - needs transporters to cross cell membranes
* less toxic
* at blood pH of 7.4 - more prominent
Ammonia NH3+
* lipophilic, easlily crosses cell membranes
* more toxic
NH3+ + H+ >< NH4+
By what pathways is ammonia produced in the intestines?
- GI bacteria containing urease –> produce ammonia from urea
- Enterocytes rich in glutaminase –> break down glutamine to ammonia and glutamate
What are the two pathways for ammonia detoxification in the liver?
Urea cycle
* periportal hepatocytes
* converts ammonia to urea
* low affinity, high capacity
* urea is water soluble, less toxic and easily excreted by the kidneys
Glutamine synthesis
* perivenous hepatocytes
* glutamine synthetase produces glutamine from ammonia
* high affinity, low capacity
How do kidneys affect the net ammonia levels
Can cause gain or loss of ammonia
glutaminase –> produces ammonia from glutamine and then excretes it
glutamine synthetase –> can produce glutamine from ammonia
How does muscle wasting in patients with liver cirrhosis increase the risk of hepatic encephalopathy in
skeletal muscles can serve as ammonia sink
large quantities of glutamine synthetase
Explain the brain’s ammonia handling
Brain has glutaminase and glutamine synthetase activity
neurons - glutaminase
astrocytes - glutamine synthase - remove ammonia, make glutamine and release it into the circulation
Explain the theories behind ammonia causing hepatic encephalopathy
- Ammonia removal by astrocytes - causing atrocyte swelling, suspected to be due to glutamine accumulation, functioning as a osmolyte
- Astrocyte exposure to ammonia causes glutamate release
- Prolonged astrocyte exposure to ammonia –> glutamate receptor downregulation
- Ammonia may increase the BBB permeability
Explain risks for SIRS in patients with hepatic encephalopathy and how SIRS can worsen hepatic encephalopathy
- bacterial translocation
- cirrhosis leading to immuno-paralysis
- ammonia interfers with neutrophil’s chemotaxis and phagocytosis
- inflammatory mediators exacerbate effects of ammonia on the cerebrum
- ammonia + endotoxemia –> preprime neutrophils –> enhances migration of neutrophils past BBB
- neutrophils –> produce inflammatory mediators that increase BBB permeability –> enhances ammonia diffusion to astrocytes
Where and how are neurosteroids synthesized?
- synthesized in the central and peripheral NS from cholesterol or other steroid hormone metabolites
- synthesized in the mitochondrial endoplasmic reticulum of myelinated cells (e.g., astrocytes) and neurons
Explain how neurosteroids are suspected to play into the pathophysiology of hepatic encephalopathy
neurosteroid synthesis upregulated through ammonia and manganese (accumulating in liver disease) activating the pripheral-type benzodiazepine receptor
PTBR regulate neurosteroid synthesis
neurosteroids as modulators of GABA-A receptors
List precipitating factors for hepatic encephalopathy
- Sepsis
- Gatrointestinal bleeding
- Constipation or bowel obstruction
- Excess dietary protein
- Hypokalemia
- Hyponatremia
- Dehydration
- Drugs
- Alkalosis
- Poor medical compliance (lactulose)
- Blood transfusion
List all mechanisms by which lactulose helps treat hepatic encephalopathy
- traps ammonium ions within the colon –> decreased absorption
- inhibition of ammonia production by colonic bacteria
- stimulation of ammonia incoorporation into bacterial proteins
- decreased intestinal transit times –> decreased bacterial ammonia release
- increased fecal excretion of nitric oxide compounds
