3. Introduction
spectrum of neuropsychiatric abnormalities
in patients with liver dysfunction, after
exclusion of other known brain disease
is a potentially reversible, or progressive,
neuropsychiatric syndrome characterized
by changes in cognitive function, behaviour,
and personality, as well as by transient
neurological symptoms and characteristic
EEG patterns associated with acute and
chronic liver failure. 7 December, 2014
4.
Clinical spectrum ranges from minor signs of altered
brain function to deep coma.
It occurs in approximately 30-45% of patients with
cirrhosis and 10-50% of patients with TIPS, while
minimal HE affects approximately 20-60% of patients
with liver disease.
prevalence of minimal hepatic encephalopathy
detectable on formal neuropsychological testing is
60–80%;
7 December, 2014
Epidemiology
5.
Hippocrates (460-370 BC) described a patient with
hepatitis who ‘barked like a dog, could not be held
and said things which could not be comprehended’.
Giovanni Battista Morgagni (1682–1771) reported in
1761 that it was a progressive condition.[15]
West Haven classification was formulated by Prof
Harold Conn and colleagues at Yale University while
investigating the therapeutic efficacy of lactulose
7 December, 2014
History
6. Classification of HE
Type A: HE associated with Acute liver failure
Type B: HE associated with portal-systemic
Bypass, no intrinsic hepatocellular disease
Type C: HE associated with Cirrhosis and portal
hypertension or portal-systemic shunts:
Episodic HE: precipitated, spontaneous, recurrent
Persistent HE: mild, severe, treatment-dependent
Minimal HE
7 December, 2014
7.
Disorder of astrocyte function
Ammonia hypothesis
Accumulation of neurotoxic substances (FNT)
GABA hypothesis
7 December, 2014
Aetiopathogenesis
8. FNTs & HE
phenylethanolamine
octopamin
NA
Dopamine
7 December, 2014
competitive Reticular formation:
maintain excitation of
cerebral cortex
Nerve pulse
transfer↓
coma
9.
--major inhibitory neurotransmitter
Evidence
Patients: GABA-ergic tone ↑
Flumazenil related research
Causes
Decreased hepatic metabolism of GABA
Gut wall permeability ↑
Advanced HE
7 December, 2014
GABA hypothesis
10. Glucose
choline
Pyruvate AcetylCoA
Lactic acid acetylcholine
Oxaloacetat
Citrate
α-ketoglutatrate
Succinate
NADH
NAD+ ATP ADP
Glutamate Glutamine
NADH
GABA
NAD+
NADH NAD+
CoA
④ ⑤
⑥
⑦
NH3
NH3
Early
Later
7 December, 2014
11.
GABA in CNS ↑ ＋ GABA/ BZ•receptor/Chloride
Ionophore Complex ↑
Cl – increase in neuron
membrane •hyperpolarization
Inhibitory postsynaptic potential
Coma
7 December, 2014
GABA & HE
12. Clinical features
Symptoms
Change in personality,
emotion, consciousness
Inability to concentrate
Confusion
Disorientation
Drowsiness
Slurring of speech
Coma
Signs
Asterixis
Constructional aprasia
Hyper-reflexia
Bilateral planter
extensor responses
Inability to perform
simple mental
arithematic task
7 December, 2014
13. Clinical grading of HE
Clinical grade Clinical signs Flapping tremor
Infrequent at this
stage
Alert, euphoric, occasionally
depression. Poor concentration,
slow mentation and affect,
reversed sleep rhythm.
Grade 1
(prodrome)
Drowsiness, lethargic, Easily elicited
inappropriate behavior,
disorientation.
Grade 2
(impending
coma)
Stuporose but easily rousable, Usually present
marked confusion, incoherent
speech
Grade 3
(early coma)
Coma, unresponsive but may Usually absent
respond to painful stimulus
Grade 4
(deep coma)
7 December, 2014
14. Clinical patterns of HE in
CLD
Type Features
No easily identifiable clinical
features.
EEG changes present
Minimal
Discrete episode with full recovery
within 4 weeks precipitated or
spontaneous.
Acute
Treatment responsive
Persistent
Severe
Chronic
7 December, 2014
15. Precipitant of HE
Metabolic Drugs Others
alteration
Nitrogen
products
GI bleeding Hypokalemia Opiates Infections
Hyperazotemia Alkalosis Benzodiazepines Surgery
Constipation Hypoxia Diuretics Renal failure
High-protein diet Hyponatremia Sedatives Short fatty acids
Superimposed
hepatic injury
H. Pylori Hyperkalemia Phenol
Uraemia Dehydration Alcohol
Rarely,hepatoma
and/or vascular
occlusion
Porto-systemic Hypoglycemia
shunt creation
(7i Dneccelumdbeirn, 2g01 4TIPPS)
17. • Urea, crt, electrolyte
• Increased blood NH3
• CSF
– Usually clear and under normal pressure
– May be increased protein conc. but cell count is
normal
– Glutamic acid and glutamine may be increased
Electroencephalogram
High amplitude
Low frequency waves
Triphasic waves
CT/MRI
7 December, 2014
Investigations
18.
Correct the precipitant
Lactulose (15-30 mL 8-hourly)
Haloperidol as sedative
Antibiotics: neomycin Neomycin (1-4 g 4-6-hourly,
metronidazole
Zinc sulfate, zinc acetate 600mg
Sodium benzoate, sodium phenybutyrate
Avoid medication that depress the CNS
Diet that contain vegetable protein than animal protein
7 December, 2014
Treatment
19.
Davidson’s:principles and practice of medicine; 21st
ed,UK, London, 2010
www.medscape.com/reference/hepatic_encephalop
athy
Kumar and Clark: clinical medicine
7 December, 2014
References
