Transcript Hepatic encephalopathy

Hepatic insufficiency
Severe damage in liver cells will result in serious
dysfunction in metabolism, secretion, synthesis,
detoxification and immune system, manifesting as
jaundice, bleeding, infection , renal dysfunction
and encephalopathy. The syndrome is called
hepatic insufficiency.
Acute and chronic
Hepatic failure is the terminal stage of hepatic
insufficiency.
Hepatic dysfunction
Injury of hepatocytes and hepatic dysfunction
metabolic dysfunction carbohydrate, protein and electrolyte
dysfunction of bile secretion and excretion
coagulation system dysfunction
biological transforming dysfunction
drug and hormone metabolism, detoxification
Injury of stromal cells and hepatic dysfunction
immune dysfunction
hepatic fibrosis
microcirculation dysfunction
Etiology
Biological factors
HBV, bacteria, parasites
Chemical factors
industrial toxins, drugs, alcohol
Nutritional factors
Inherited factors
Wilson’s disease
Immune factors
AIH
Hepatic encephalopathy
Hepatic encephalopathy is a complex, potentially
reversible disturbance in central nervous system
that occurs as a consequence of severe liver
diseases.
It is generally divided into four stages,
manifestating from slightly altered mood or
behavior, through to somnipathy, and
inappropriate behavior, to drowsy and
psychopathy, and even finally to deep coma.
Pathogenesis
Ammonia intoxication hypothesis
False neurotransmitter hypothesis
Amino acid imbalance hypothesis
The gamma-aminobutyric acid hypothesis
Ammonia intoxication hypothesis
Causes for elevated ammonia
Decreased ammonia clearance
impaired Krebs-Henseleit urea cycle
Increased ammonia production
urea in the blood is emitted into intestinal lumen
and degraded by urease in bacteria to produce
ammonia
ammonia is produced in the kidneys and muscles
gastrointestinal hemorrhage and absorption
dysfunction
Intoxication of ammonia on the brain
Impairment of energy metabolism in brain
ammonia reacts with α-ketoglutatrate to produce
glutamate and glutamine
consumption of α-ketoglutatrate, NADH and ATP, inhibition
of pyruvate decarboxylase leading to the reduction of acetyl
CoA and acetylcholine
Alteration of neurotransmitters
decreased excitatory neurotransmitters
glutamate and acetylcholine
increased inhibitory neurotransmitters
glutamine and gamma-aminobutyric acid
Inhibiting action on nerve cell membrane
False neurotransmitter hypothesis
phenylalanine → phenylethanolamine
tyrosine → octopamine
Dopamine and norepinephrine
Amino acid imbalance hypothesis
BCAA/AAA↓
Insulin↑, glucagon ↑ ↑, insulin/glucagon ↓
Increased production of aromatic AA and increased
uptake and utilization of branch chain AA
Inhibiting the production of normal neurotransmitters
Promoting the production of false neurotransmitters
Increased production of 5-hydroxytryptophan(5-HT)
The gamma-aminobutyric acid hypothesis
GABA
Inhibitory neurotransmitters
Decarboxylase
↓
Glutamate →GABA
Precipitating factors
Overload of Nitrogen
digestive tract hemorrhage
Increased permeability of blood brain barrier
endotoxin
Increased sensibility of brain
narcotics and sedatives
Prevention and treatment
Eliminating or correcting precipitating factors
Reducing plasma ammonia
Correcting plasma amino acid imbalance and
supplying normal neurotransmitters
Liver transplantation
Hepatorenal syndrome
Hepatorenal syndrome is referred to the
development to renal failure in patients with
severe liver disease in absence of any other
identified cause of renal pathology.
Pathogenesis
Stimulated sympathetic nervous system
Activated renin-angiotensin system
Abnormal function of kinin system
Action of PGs
Endothelin-1
Endotoxin
False neurotransmitters