Hepatic Encephalopathy Flashcards
How are the causes of HE categorized?
- type A (acute): due to acute liver failure in the absence of preexisting liver disease.
- B (bypass): portal systemic bypass without
intrinsic hepatocellular disease (eg, CPSS) - C (chronic/cirrhosis): associated with cirrhosis and portal hypertension
or acquired portal systemic shunting; subcategorized
according to duration/characteristics.
How is Ammonium different from Ammonia?
Ammonia= lipophilic and highly lipid-soluble, passes freely across cell memb. Ammonium ions= not lipid-soluble= must be transported across cellc memb by carrier-mediated systems
Where does ammonia come from?
breakdown of dietary proteins
by urease-producing bacteria in the GI tract.
Glutamine is metabolized
to glutamate and ammonia
(glutamine = glutamate + NH3) by glutaminase (mainly present in enterocytes)
How is ammonia metabolized?
2 ways:
1. Urea cycle= conversion to urea in the periportal hepatocytes= low affinity, high capacity
2. Transamination within perivenous hepatocytes, brain, and skeletal muscle. = addition of ammonia to glutamate via glutamine synthase producing glutamine= high affinity, low capacity
Why is loss of skeletal muscle a predisposing factor for development of HE?
skeletal muscle is the tissue with the most quantitatively important source of glutamine synthetase (uses ammonia to produce glutamine)= acts as ‘ammonia sink’
What cell type in the CNS can remove ammonia?
Astrocytes (high glutamine synthetase activity)= transform glutamate (major excitatory neurotransmitter) in glutamine
How does hyperammonemia affect the brain?
- Ammonia inhibits glutamine release from astrocytes. Glutamine is osmotically active and causes cytotoxic edema by inserction of specific aquaporin-4 channels into astrocyte cell memb (SACCM)
- Acute hyperammonemia promotes release of glutamate= excitation VS chronic promotes downregulation of glutamate-binding sites and glutamate transporters= depression
- Increases BBB permeability
Describe the ‘Trojan horse’ hypothesis for HE
The accumulated intracell glutamine moves
into the mitochondria, where deamination occurs producing glutamate
and ammonia. This process leads to the deleterious production
of reactive O2 and nitrogen species secondary to ammonia liberation.
What are the most common precipitating factors for HE?
- high protein
meal - GI hemorrhage
- hypokalemia
- azotemia and/or dehydration
- alkalosis
- diuretic administration
- blood transfusion
- sedative use
- systemic inflammation
and/or infection - In cats: arginine deficiency
T/F: Normal pre- and postprandial bile acids with normal ammonia
concentration in symptomatic dogs effectively rule out HE
True (SACCM)
What can be used as a biomarker of hepatic function and perfusion?
anticoagulant protein C (it’s synthetized by the liver) (SACCM)
What role do neurosteroids play in HE?
- Steroid hormones found in high conc in the brain.
Produced both centrally and peripherally. - Synthesis is regulated by the peripheral type
benzodiazepine receptor (PTBR) - In HE, PTBR are upregulated in the brain
- NS act of GABA-A receptors
How does GABA work in the CNS?
receptor binding leads to an increased Cl- influx
and hyperpolarization
Name 4 nonammonia contributors to HE
- neurosteroids
- oxidative stress
- manganese
- ## increase conc of aromatic amino acids (AAA)
What is the role of aromatic amino acids in HE?
In patients
with liver dysfunction or PSS, the ability to convert aromatic amino
acids to the typical neurotransmitters may be overwhelmed. In this
situation, false neurotransmitters (e.g., octopamine, phenylethanolamine)
may be synthesized that exert an inhibitory effect.
