Chapter 14

Hepatic failure & Hepatic

encephalopathy
 Change Process
• hepatic insufficiency

stage

•Hepatic failure
 HBV Disease Continuum

Resolution Stabilization Compensated

Death
Acute Chronic
infection Hepatitis Cirrhosis HCC

Asymptomatic Decompensation
carrier Transplantation
Death
30–50 years
•

Liver diseases
 Etiology of Hepatic failure
1.biological: ?
2.physical and chemical
3.inherital(congenital):Wilson's disease, inability to e
xcrete copper into bile, toxic accumulation of copper ;
Hemochromatosis, iron overload syndrome
4.immunol: autoimmune hepatitis and primary biliary cirr
hosis
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
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

pH 
NH3 NH4+
pH
2% 98%
(1) NH3 increased in hepatic encephalopathc
y
 ? ??

reasons of blood NH3 ↑

NH 3 r
↑
igin

emov
3 or
NH

ng ↓ i
 NH3 origin ↑ NH3 removing ↓

Enteric ↑ Urea synthesis ↓

e r
liv
Renal Plasma Lateral
↑ ↑ NH3 ↑ circulation↑
backflow↑

Skeleton
muscle↑ Glutaminne synthesis ↓
 UREOGENESIS
AMMONIA
Citrulline Aspartic acid

UREA
CYCLE
Ornithine Arginine

UREA Ureogenesis takes place

in the liver and is essential
for ammonia detoxification
 Hepatic
NH3 Extrahepatic
detoxification detoxification
of ammonia of ammonia

Ornithine Citrulline
UREA Aspartic acid
CYCLE Asparagine Glutamic acid
Glutamine
Arginine

UREA
NH3
URINE
(2) NH3 toxicity on CNS

NH3 ↑interferes with

①cerebrocellular energy: ？
② neurotransmitter imbalance
③neurocellular membrane ion transferring
α-ketoglutaric acid+ NH3
NA
DH

glutamic acid+ NH3

ATP
glutamine

Process of deceasing NH3 in brain

Exiting inhibition
***synergistic effect of neurotoxin
neurotoxin 

• Mercaptan(metheonine)
• NH3 cerebral energy
cerebral cell respiratio
• Indole (tryptophan)
Na+ pump
• Phenol(tyrosine,tyramin neural impulse delivery
e)
synapse intoxication
• monoamine
• Short chain fatty ac
id
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 ( Nor
> 3 ) → ?CNS disorder

AAA ： aromatic amino acid

BCAA: branch chain amino acid
Liver deactivation ↓
uptake & utilizing
BCAA↑in tissue
insulin↑

glucagon ↑ protein decomposed↑

in muscle & liver

Blood NH3↑

glyconeogenesis↓ AAA↑
(2) FNT formation

phenylalanine decarboxylation phenylalamine MAO

Tyrosine
tyramine  ?
in liver

BBB
Tyrosine
hydrogenase in brain β- hydrogenase

dopa

β -phenylethanolamine 、
octpamine ↑
dopamine
NE （ FNT ）
 Comparison between TNT and FNT

HO CHOHCH2NH2 CHOHCH2NH2

HO

noradrenaline
phenylethanolamine

HO CHCH2NH2 CHOHCH2NH2

HO HO

dopamine
octopamine
 (3) plasma amino acid imbalance
and FNT formation

blood glutamine
antiport

AAA ↑
BCAA ? FNT
tryptophan ↑
tryptamine
BB
B 5-HT
3. GABA alteration and HE

transferaminase
decarboxygenase
Glutamatic acid GABA succinic acid
－ semialdehyde
+
NH3 ↑
NH3↑

early stage late stage

• GABA molecular structure
 Part 3 precipitating factors
• 1.gastrointestinal bleeding
• 2.abuse of sedative and narcotic
• 3.massive paracentesis and excessive diures
is
• 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