Upload
iko-musa
View
301
Download
2
Tags:
Embed Size (px)
Citation preview
Introduction
Epedimiology
Classification
Aetiopathogenesis
precipitant
Clinical features
Differential diagnosis
Investigation
Treatment
7 December, 2014
Outline
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
Introduction
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
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
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
Classification of HE
Disorder of astrocyte function
Ammonia hypothesis
Accumulation of neurotoxic substances (FNT)
GABA hypothesis
7 December, 2014
Aetiopathogenesis
FNTs & HE
7 December, 2014
phenylethanolamine
octopamin
NA
Dopamine
competitive Reticular formation:
maintain excitation of cerebral cortex
Nerve pulse
transfer↓
coma
--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
Glucose
Pyruvate AcetylCoA
Oxaloacetat
Citrate
α-ketoglutatrate
Succinate
Glutamate Glutamine
Lactic acid acetylcholine
NADH
NAD+ ATP ADP
GABA
NADH
NAD+
NADH NAD+
CoA
choline
⑤④
⑥
⑦
NH3
NH3
Early
Later7 December, 2014
GABA in CNS ↑ + GABA/ BZ•receptor/Chloride
Ionophore Complex ↑
Cl – increase in neuron
membrane •hyperpolarization
Inhibitory postsynaptic potential
Coma
7 December, 2014
GABA & HE
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
Clinical grading of HE
Flapping tremorClinical signsClinical grade
Infrequent at this stage
Alert, euphoric, occasionally depression. Poor concentration, slow mentation and affect, reversed sleep rhythm.
Grade 1
(prodrome)
Easily elicitedDrowsiness, lethargic, inappropriate behavior, disorientation.
Grade 2
(impending coma)
Usually presentStuporose but easily rousable, marked confusion, incoherent speech
Grade 3
(early coma)
Usually absentComa, unresponsive but may respond to painful stimulus
Grade 4
(deep coma)7 December, 2014
Clinical patterns of HE in CLD
Features Type
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
OthersDrugsMetabolic
alterationNitrogen products
InfectionsOpiatesHypokalemiaGI bleeding
SurgeryBenzodiazepinesAlkalosisHyperazotemia
Renal failureDiureticsHypoxiaConstipation
Short fatty acidsSedativesHyponatremiaHigh-protein diet
Superimposed hepatic injury
PhenolHyperkalemiaH. Pylori
Alcohol DehydrationUraemia
Rarely,hepatoma and/or vascular occlusion
Hypoglycemia Porto-systemic shunt creation (including TIPPS)7 December, 2014
Precipitant of HE
7 December, 2014
Differential diagnosis
Severe hyponatremia
Respiratory failure
Severe sepsis
Intracranial bleed
Acute alcoholism
Wernicke’s encephalopathy
Status epilepticus
Zinc deficiency
Drug overdose
Hypoglycemia
Post ictal
CNS sepsis
Delirium tremens
Hepato-lenticular degeneration (Wilson’s disease)
Functional psychoses
• 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/MRI7 December, 2014
Investigations
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
Davidson’s:principles and practice of medicine; 21st
ed,UK, London, 2010
www.medscape.com/reference/hepatic_encephalopathy
Kumar and Clark: clinical medicine
7 December, 2014
References