Chapter 14
Hepatic failure & Hepatic encephalopathy
Change Process • hepatic insufficiency stage
•Hepatic failure
HBV Disease Continuum Resolution
Chronic Hepatitis
Compensated
Death
Acute infection
Stabilization
Cirrhosis
Asymptomatic carrier
30–50 years
HCC
Decompensation Transplantation Death
•
Liver diseases
Etiology of Hepatic failure 1.biological: ? 2.physical and chemical 3.inherital(congenital):Wilson's disease, inability to excrete copper into bile, toxic accumulation of copper ; Hemochromatosis, iron overload syndrome
4.immunol: autoimmune hepatitis and primary biliary cirrhosis 5.nutritional: starvation & obesity
Section 1 hepatic insufficiency
Hepatic function & dysfunctions 1. metabolism: 2.secreting & excreting: 3.detoxication & defense 4.coagulation 5.affecting other organ hepatic encephalophcy
Section 2 hepatic encephalopathy
Part 1 etiology and classification
Major types of hepatic encephalophcy ①Acute fulminant type: hepatic necrosis ②Chronic recurrent type: cirrhosis
Iran overload
Chronic hepatic encephalopathy ①prodromal ~: mood & behavior ②precoma ~: drowsy, asterixis ③stuporous ~: speaking and obeying simple commands ④coma ~: no response to painful stimuli
Part 2
pathogenesis
mechanisms of hepatic encephalopathcy
hypothesis ①toxication: NH3 ↑, synergistic action of neurotoxin ②false neurotransmitter & plasma amino acid imbalance: BCAA/AAA ratio ↓ ③ neurotransmitter imbalance: GABA ↓ ↑
1.NH3 intoxication • Normal: plasma NH3 < 100μg ％， • 80~90 ％ of patient: 2~3 folds(200~500 μg ％），
Blood ammonia configuration
NH3 2%
pH ↓ pH↑
NH4+ 98%
(1) NH3 increased in hepatic encephalopathcy
? ??
ng ↓
3
NH
i emov NH 3 r
orig in ↑
reasons of blood NH3 ↑
NH3 removing ↓
NH3 origin ↑
Enteric ↑
Renal backflow↑ Skeleton muscle↑
r e liv Plasma ↑ NH3
↑ ↑
Urea synthesis
Lateral circulatio n↑
Glutaminne synthesis
UREOGENESIS AMMONIA Aspartic acid
Citrulline UREA CYCLE Ornithine Arginine UREA
Ureogenesis takes place in the liver and is essenti for ammonia detoxificatio
Hepatic detoxificat ion of ammonia Ornithine Citrulline UREA CYCLE Arginine
NH3
Extrahepa tic detoxificat ion of ammonia
Aspartic acid Asparagine Glutamic acid Glutamine
UR EA URINE
NH3
(2) NH3 toxicity on CNS NH3 ↑interferes with ①cerebrocellular energy: ？ ② neurotransmitter imbalance ③ neurocellular membrane ion transferring
α-ketoglutaric acid+ NH3 NA DH
glutamic acid+ NH3 glutamine
ATP
Process of deceasing NH3 in brain
Exiting
inhibition
***synergistic effect of neurotoxin neurotoxin
• Mercaptan(metheonine) cerebral energy • NH3 cerebral cell respiration • Indole (tryptophan) Na+ pump • Phenol(tyrosine,tyramine) neural impulse delivery synapse intoxication • monoamine • Short chain fatty acid decay products of enteric bacteria
2. False neurotransmitter(FNT) & plasma amino acid imbalance (1) Reasons of plasma amino acid imbalance
blood AAA/BCAA imbalance Serious liver disease ， BCAA/AAA ratio ↓ < 1
> 3 ) →
?CNS
( Nor
disorder
AAA ： aromatic amino acid BCAA: branch chain amino acid
Liver deactivation ↓ insulin↑
glucagon ↑
uptake & utilizing BCAA↑in tissue
protein decomposed↑ in muscle & liver
Blood NH3↑
glyconeogenesis↓
AAA↑
(2) FNT formation phenylalaninedecarboxylation Tyrosine
phenylalamineMAO
tyramine
×
?
in liver
BBB Tyrosine hydrogenase
in brain
β-
hydrogenase
dopa β -phenylethanolamine 、 dopamine
NE
octpamine ↑ （ FNT ）
Comparison between TNT and FNT HO
CHOHCH2NH2
CHOHCH2NH2
HO
noradrenaline
HO HO
dopamine
phenylethanolamine
CHCH2NH2
CHOHCH2NH2 HO
octopamine
(3) plasma amino acid imbalance and FNT formation
blood
glutamine antiport
AAA ↑ BCAA↓ tryptophan ↑
? BB B
FNT
tryptamine
5-HT
3. GABA alteration and HE
Glutamatic acid
decarboxygenase
transferaminase
GABA
+
NH3 ↑
early stage
NH3↑
late stage
succinic acid semialdehyde
• GABA molecular structure
Part 3 precipitating factors • 1.gastrointestinal bleeding • 2.abuse of sedative and narcotic • 3.massive paracentesis and excessive diuresis • 4.infection
Part 4 principle of prevent and treatment (1) protect hepatic cell (2)decrease NH3 : benzoate, lactulose (3)restore plasma amino acid balance (4)increase normal neurotransmitter L-dopa
Acute liver failure! • Support – – – – – – –
CNS Respiration Circulation CRRT/MARS Coagulation Infection Metabolism