hepatic encephalopathy.ppt

8/19/2019 hepatic encephalopathy.ppt

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HepaticHepatic

EncephalopathyEncephalopathy


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Hepatic encephalopathyHe

patic encephalopathy (HE)(HE)

► a reversible neuro-psychiatric statea reversible neuro-psychiatric state

► a complication of liver failurea complication of liver failure

► pathogenesis is not understood fullypathogenesis is not understood fully► derangement of neurotransmitterderangement of neurotransmitter

system and metabolic systemsystem and metabolic system


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PathogenesisPatho

genesis ►

No single metabolic derangement accounts for HE.No single metabolic derangement accounts for HE.

► Failure of hepatic clearance of gut derivedFailure of hepatic clearance of gut derived

substances.substances.

►Hepatocellular failure or shunting.Hepatocellular failure or shunting.

► Altered aminoacid metabolism.Altered aminoacid metabolism.► Accumulation of unmetabolied ammonia !ry toAccumulation of unmetabolied ammonia !ry to

poor hepatic function or shunt.poor hepatic function or shunt.

►

Production of false neurotransmitters.Production of false neurotransmitters.► Activation of "A#A-#eno receptors byActivation of "A#A-#eno receptors by

endogenous ligands.endogenous ligands.

► Altered cerebral metabolism.Altered cerebral metabolism.

►$isturbed activity of Na%& A'Pase.$isturbed activity of Na%& A'Pase.


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PathogenesisPatho

genesisScarring of liver( cirrhosis)

Obstruction of the passage of blood (liver) portal hypertension

Portal-systemic anastomoses ("shunts“)

Bypasses liver

Return to heart

o!ic substances enters brain

mpending hepatic coma


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lassication of hepaticlassication of h

epatic

encephalopathyenc

ephalopathy

(*orld ongress of "astroenterology(*orld ongress of "astroenterology

+,, in ienna )+,, in ienna )

1.1. Type A (=acute)Type A (=acute) describes hepaticdescribes hepatic

encephalopathy associated /ithencephalopathy associated /ith

acute liver failure0acute liver failure0

2.2. Type B (=bypass)Type B (=bypass) is caused byis caused by

portal-systemic shunting /ithoutportal-systemic shunting /ithout

associated intrinsic liver disease0associated intrinsic liver disease0

3.3. Type C (=cirrhosisType C (=cirrhosis) occurs in) occurs in

patients /ith cirrhosis .patients /ith cirrhosis .


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lassication of hepaticlassication of h

epatic

encephalopathyen

cephalopathy

'ype '

ype Aetiological factors

Aetiolo

gical factorsA(!12) iral hepatitis3A(!12) iral hepatitis3

Alcoholichepatitis3Alcoholichepatitis3

$rug reacns 4overdose.$rug reacns 4overdose.

#(+112) Portal systemic shunt3#(+112) Portal systemic shunt3 $ietary protein inta5e3$ietary protein inta5e3

6ntestinal bacteria.6ntestinal bacteria.

(782) $iuresis3(782) $iuresis3 Haemorrhage3Paracentesis3Haemorrhage3Paracentesis3

$iarrhoea39urgery39edatives3$iarrhoea39urgery39edatives3

9epsis3onstipation.9epsis3onstipation.


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Neurotansmitters implicated inNeurotansmitters implicated in

HEHE►Ammonia and "lutamateAmmonia and "lutamate►:anganese3 :ercaptans3Phenols3:anganese3 :ercaptans3Phenols3

►

False neurotransmittersFalse neurotransmitters►"A#A and Endogenous #;$"A#A and Endogenous #;$

►ideide


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Ammonia and "lutamateAmmonia and "lutamate

► Ammonia is produced from brea5do/n ofAmmonia is produced from brea5do/n of

proteins3 amino acids3 purines3 pyrimidines.proteins3 amino acids3 purines3 pyrimidines.

► ?iver converts ammonia to urea and?iver converts ammonia to urea and

glutamate by urea cycleglutamate by urea cycle

► 6n HE3 blood NH6n HE3 blood NH@@ by ,12 also brain levels by ,12 also brain levels

► 'here is no urea cycle in the brain 4 NH 'here is no urea cycle in the brain 4 NH@@ isis

removed by di path/ayremoved by di path/ay► NHNH@@ leads to :B and ###leads to :B and ###

permeability to NHpermeability to NH@@


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Ammonia and "lutamateAmmonia and "lutamate C C

contdcontd

HepaticHepatic

encephalopathyencephalopathy

► increase in cerebralincrease in cerebral

ammoniaammonia

►astrocyte damageastrocyte damage

►reduced glutamatereduced glutamate

receptorsreceptors

►glutamineglutamine

accumulatesaccumulates

A t t


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Ammon a an utamatemmon a an u ama e C Ccontdcontd

9


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:anganese 4:anganese 4

false neurotransmittersfalse neurotransmitters►#lood 4 #rain :n levels increased in ?F#lood 4 #rain :n levels increased in ?F

►Normally produced dopamine 4Normally produced dopamine 4

catecholamines mediated neuroaminescatecholamines mediated neuroamines

are inhibited by false neurotransmittersare inhibited by false neurotransmitters

(tyramine3octopamine)(tyramine3octopamine)

►Plasma levels of aromatic a.a 4Plasma levels of aromatic a.a 4

branched chain a.abranched chain a.a


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"A#A 4 Endogenous #;$"A#A 4 Endogenous #;$

►"A#A is principal inhibitory amine"A#A is principal inhibitory amine► 6t binds to specic "A#A receptor in6t binds to specic "A#A receptor in

postsynaptic membpostsynaptic memb

►Beceptor also has binding site forBeceptor also has binding site for#;$ 4barbiturates#;$ 4barbiturates

►"A#A 4 Endogenous #;$ are high in"A#A 4 Endogenous #;$ are high in

plasma 49F of liver failure ptsplasma 49F of liver failure pts► 'hese leads to hyperpolarisation 'hese leads to hyperpolarisation

4neuroinhibition4neuroinhibition


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9ymptoms 4 9igns9ymptoms 4 9igns

+.+. Earliest manifestations of hepaticEarliest manifestations of hepatic

encephalopathy is day-night Beversalencephalopathy is day-night Beversal

!.!. 6mpairment in spatial perception6mpairment in spatial perception

@.@. hanged cognitive function Gmildhanged cognitive function Gmild

confusion to comaconfusion to coma

.. Flapping tremor (asteri>is )Flapping tremor (asteri>is )

8.8. E>aggerated deep tendon reIe>esE>aggerated deep tendon reIe>es

4sustained an5le clonus4sustained an5le clonus


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Acute liver failureAcute liver failure

($epending on onset of encephalopathy($epending on onset of encephalopathy

4 onset of Jaundice)4 onset of Jaundice)

►

Hyperacute - less than 7daysHyperacute - less than 7days

►Acute - 7 to ! daysAcute - 7 to ! days

►9ubacute - !days to Kmonths9ubacute - !days to Kmonths

►hronic - more than K monthshronic - more than K months


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6nvestigations6nvestigations

► 9F analysis =cell count3protein39F analysis =cell count3protein3

glutamatic acidglutamatic acid

► Electroencephalogram =b%l synchronousElectroencephalogram =b%l synchronous

slo/ing of /avesslo/ing of /aves

► Evo5ed potentialsEvo5ed potentials

► #rain scans#rain scans

►:agnetic resonance spectroscopy:agnetic resonance spectroscopy

►NeuropathologyNeuropathology


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'reatment of Hepatic 'reatment of Hepatic

encephalopathyencephalopathy #roadly divided into @ areas#roadly divided into @ areas

+.+. 6dentication 4 treatment of ppt6dentication 4 treatment of ppt

factorsfactors

!.!. 6nterventions to reduce the6nterventions to reduce the

production of 4 absorption of gutproduction of 4 absorption of gut

derived ammonia 4 other to>insderived ammonia 4 other to>ins

@.@. Prescription of agents to modifyPrescription of agents to modify

neurotransmittersneurotransmitters


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Beduction of absorption and production ofBeduction of absorption and production of

ammoniaammoniaProtein restriction to 20g/day then increase 10g /3-5 days andProtein restriction to 20g/day then increase 10g /3-5 days and

evaluate tolerance.evaluate tolerance.

Supplementation with vegetable protein is important in patientsSupplementation with vegetable protein is important in patients

with low tolerance.!elated to "iber/protein ratio#with low tolerance.!elated to "iber/protein ratio#

!eduction o" endogenous intestinal cells shedding# and dietary!eduction o" endogenous intestinal cells shedding# and dietaryammoniagenics by cathartics $actulose and $actitol#.ammoniagenics by cathartics $actulose and $actitol#.

%ose titrated to 2-& loose/acidic stools/day generally re'uiring 30-%ose titrated to 2-& loose/acidic stools/day generally re'uiring 30-(0grams/day.(0grams/day.

$actulose 10-30ml tid#$actulose 10-30ml tid#))

1- %ecreases *ntestinal P+. ,avors growth o" non-urease1- %ecreases *ntestinal P+. ,avors growth o" non-urease

producing bacteria.producing bacteria. 2- Promotes movement o" ammonia "rom blood to bowel2- Promotes movement o" ammonia "rom blood to bowel

and decreased absorption.and decreased absorption.

$actilol 0.3-0.5g/g/day#responds more 'uiclyless diarrhoea $actilol 0.3-0.5g/g/day#responds more 'uiclyless diarrhoea "latulence"latulence


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Beduction of absorption and production ofBeduction of absorption and production of

ammoniaammonia ntibioticsntibiotics ))

eomycin &-( gr /day #"or 5- days in acute caseseomycin &-( gr /day #"or 5- days in acute cases reduces ammonia "ormation in 4*reduces ammonia "ormation in 4*

care"ul in !,#care"ul in !,#

6etronida7ole200 mg 8id #6etronida7ole200 mg 8id #

!i"a9imin or brand name :i"a9an a derivative o" ri"amycin at a dose o" &00!i"a9imin or brand name :i"a9an a derivative o" ri"amycin at a dose o" &00

mg taen orally 3 times a day was as e""ective as lactulose or lactilol atmg taen orally 3 times a day was as e""ective as lactulose or lactilol atimproving hepatic encephalopathy symptoms. Similarly ri"a9imin was asimproving hepatic encephalopathy symptoms. Similarly ri"a9imin was ase""ective as neomycin and paromomycin. !i"a9imin was better toleratede""ective as neomycin and paromomycin. !i"a9imin was better toleratedthan both the cathartics and the other nonabsorbable antibiotics. . here arethan both the cathartics and the other nonabsorbable antibiotics. . here arealso concerns regarding the cost-e""ectiveness o" the medication.also concerns regarding the cost-e""ectiveness o" the medication.

Purgation by enemas esp phosphatePurgation by enemas esp phosphate

!epopulation o" bowel with non urease producing bacteria.!epopulation o" bowel with non urease producing bacteria.

;rradication o" +. pylori.;rradication o" +. pylori.


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hepatic encephalopathy.ppt

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