7 December, 2014

Phase 2 medicine posting

PRESENTER: MUSA IKO

MODURATOR: DR BANCY

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%;

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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

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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

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Classification of HE

Disorder of astrocyte function

Ammonia hypothesis

Accumulation of neurotoxic substances (FNT)

GABA hypothesis

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Aetiopathogenesis

FNTs & HE

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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

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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

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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

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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

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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

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Treatment

Davidson’s:principles and practice of medicine; 21st

ed,UK, London, 2010

www.medscape.com/reference/hepatic_encephalopathy

Kumar and Clark: clinical medicine

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References

7 December, 2014