肝硬化英文技术报告

Slide

48ARCHITECTURAL

LIVER

DISRUPTION

IS

THE

MAIN

MECHANISM

THAT

LEADS

TO

AN

INCREASED

INTRAHEPATIC

RESISTANCEThe

deposition

of

fibrous

tissue

and

the

formationof

nodules,

disrupts

the

architecture

of

the

liver,

leading

to

an

increased

resistance

to

flow

and

to

portalhypertension.

Vessels

that

normally

drain

into

the

portal

system,

such

as

the

coronary

vein,

reverse

their

flow

and

become

porto-systemic

collaterals.

Additionally,withportal

hypertension,

the

spleen

increases

in

size

and

sequesters

platelets

and

other

formed

blood

cells

leadingto

hypersplenism.Hepatic

cirrhosisSlide

5DEFINITION

OF

CIRRHOSISCirrhosis

is

a

histological

diagnosis

and

is

defined

by

the

presence

of

nodulesof

regenerating

hepatocytes

surrounded

by

fibrous

tissue.

Although

histologicallycirrhosis

is

an

“all

or

nothing”

diagnosis,

clinically,

cirrhosis

can

be

classified

as

compensated

or

decompensated.Hepatic

CirrhosisEnd

stage

of

any

chronic

liver

diseaseCharacterized

histologically

byregenerative

nodules

surrounded

byfibrous

tissueClinically

there

are

two

types

of

cirrhosisCompensatedDecompensatedSlide

6GROSS

IMAGE

OF

A

NORMALAND

A

CIRRHOTIC

LIVERGross

images

of

two

livers.

On

the

left

a

normal

liver

with

a

smooth

surface

and

homogeneous

appearance.

On

the

right

a

cirrhotic

liver

with

an

irregular

surfaceand

nodules

that

give

it

a

heterogeneous

appearance.CirrhosisNormalNodulesIrregularsurfaceSlide

7GROSS

IMAGE

OFA

CIRRHOTIC

LIVERGross

image

of

a

cirrhotic

liver

demonstratingan

irregular

surface

and

nodules

that

give

it

a

heterogeneous

appearance.Cirrhotic

liverNodular,

irregular

surfaceNodulesGROSS

IMAGE

OF

A

CIRRHOTIC

LIVERSlide

8HISTOLOGICAL

IMAGE

OF

A

NORMAL

AND

A

CIRRHOTIC

LIVERHistological

images

of

two

livers.

On

the

left,

a

normal

liver

with

conserved

architecture.

On

the

right,

a

cirrhotic

liver

with

regenerative

nodules

surrounded

byfibrous

tissue

(stained

blue).CirrhosisNormalNodules

surrounded

byfibrous

tissueSlide

9HISTOLOGICAL

IMAGE

OF

CIRRHOSISHistological

image

of

a

cirrhotic

liver

showing

regenerative

nodules

surrounded

byfibrous

tissue

(stained

blue).FibrosisRegenerativenoduleSlide

10PATHOGENESIS

OF

LIVER

FIBROSISThe

key

pathogenic

feature

underlyingliver

fibrosis

and

cirrhosis

is

hepatic

stellate

cell

activation.

Hepatic

stellate

cells

(also

known

as

Ito

cellsorperisinusoidalcells)

are

located

in

the

space

of

Disse

between

hepatocytes

and

sinusoidal

endothelial

cells

(that

normally

are

fenestrated).

Normally,

hepatic

stellate

cells

arequiescent

and

serve

as

the

main

storage

site

for

retinoids

(vitamin

A).HepatocytesSpace

of

DisseSinusoidalendothelial

cellHepaticstellate

cellFenestraeNormal

Hepatic

SInusoidRetinoiddropletsSlide

12PATHOGENESIS

OF

LIVER

FIBROSISIn

cirrhosis,

activated

stellate

cells

deposit

collagenin

the

space

of

Disse,

leadingto

defenestration

of

sinusoidal

endothelial

cells,

and

acquire

contractile

propertiesthat

lead

to

sinusoidal

constriction,

which

is

partially

responsible

for

increased

intrahepatic

vascular

resistance.Alterations

in

Microvasculature

in

CirrhosisActivation

of

stellate

cellsCollagen

deposition

in

space

ofDisseConstriction

of

sinusoidsDefenestrationof

sinusoidsSlide

14NATURAL

HISTORYOF

CHRONIC

LIVER

DISEASECirrhosis

represents

the

end

histological

stage

resultingfromchronic

liver

injuryof

various

etiologies.

Initially,

cirrhosis

is

compensated.

The

transition

to

adecompensated

stage

is

marked

by

the

developmentof

variceal

hemorrhage,

ascites,

hepatic

encephalopathy

and/or

jaundice.

Once

decompensation

occurs,

thepatient

is

at

risk

of

death

from

liver

disease.CompensatedcirrhosisDecompensatedcirrhosisDeathChronicliverdiseaseNatural

History

of

Chronic

Liver

DiseaseDevelopment

ofcomplications:Variceal

hemorrhageAscitesEncephalopathyJaundiceSlide

16SURVIVAL

TIMES

IN

CIRRHOSISIn

aprospective

cohort

study

of

257

patients

with

compensated

cirrhosis

of

different

etiologies,

mediansurvival

for

all

patients

(including

those

who

developeddecompensation)

was

approximately

9

years,

while

it

was

significantly

lower

in

patients

who

developed

a

decompensating

event

(ascites,

jaundice,

encephalopathyor

hemorrhage),

in

whomthe

mediansurvival

was

only1.6

years.Gines

et

al.

Hepatology

1987;

7:1226040040802020060ProbabilityofsurvivalDecompensation

Shortens

Survival100Gines

et.

al.,

Hepatology1987;7:122Median

survival~

9

years

All

patients

with

cirrhosisDecompensated

Median

survivalcirrhosis

~

1.6

years80

100

120

140

160

180Months10Slide

17COMPLICATIONS

OF

CIRRHOSISCirrhosis

leads

to

two

clinical

syndromes:

portal

hypertension

and

liver

insufficiency.

Development

of

variceal

hemorrhage

and

ascites

are

the

direct

consequence

ofportal

hypertension,

while

jaundice

occurs

as

a

result

of

a

compromised

liver

function.

Encephalopathy

is

the

result

of

both

portal

hypertension(portosystemicshunting)

and

liver

dysfunction(decreased

ammonia

metabolism).

Ascites

in

turn

can

become

complicated

byinfection(spontaneous

bacterial

peritonitis)

and

by

thedevelopment

of

a

functional

renal

failure

(hepatorenal

syndrome).Variceal

hemorrhageComplications

of

Cirrhosis

Result

from

PortalHypertensionor

Liver

InsufficiencyCirrhosisAscitesEncephalopathyLiverinsufficiencyJaundicePortalhypertensionSpontaneousbacterialperitonitisHepatorenalsyndromeSlide

18DIAGNOSIS

OF

CIRRHOSISAlthough

the

definitive

diagnosis

of

cirrhosis

is

histological,

various

clinical

features,

in

the

setting

of

chronic

liver

disease,

maysuggest

the

presence

of

cirrhosis.

Ifthese

features

are

present,

the

diagnosisof

cirrhosis

can

be

confirmed

non-invasively

by

imaging

studies.

However,

the

absence

of

these

features

does

not

rule

outthe

presence

of

cirrhosis.Cirrhosis

-

DiagnosisCirrhosis

is

a

histological

diagnosisHowever,

in

patientswith

chronicliver

disease

the

presence

of

variousclinical

features

suggests

cirrhosisThe

presence

of

these

clinicalfeatures

can

be

followed

by

non-invasive

testing,

prior

to

liver

biopsySlide

19DIAGNOSIS

OF

CIRRHOSIS

–

CLINICAL

FINDINGSCirrhosis

should

be

investigated

in

any

patient

withchronic

liver

disease.

Various

physical

signs

suggest

the

presence

of

cirrhosis.

In

particular,

a

palpable

left

lobewith

asmall

right

lobe

(on

percussion)

and

splenomegaly

are

highlysuggestive

of

cirrhosis.

A

recent

review

of

several

studies

concludes

that

the

listed

physicalfindings,

when

present

in

chronic

liver

disease,

confera

high

specificity

for

cirrhosis.

However

the

sensitivityis

generallylow

and

the

absence

of

these

physical

signsdoes

not

exclude

cirrhosis.De

Bruyn

G

and

Graviss

EA,

BMC

Medical

Informatics

&

Decision

Making

2001;1:6In

Whom

Should

We

Suspect

Cirrhosis?Any

patient

with

chronic

liver

diseaseChronic

abnormal

aminotransferases

and/oralkaline

phosphatasePhysical

exam

findingsStigmata

of

chronic

liver

disease

(muscle

wasting,vascular

spiders,

palmar

erythema)Palpable

left

lobe

of

the

liverSmall

liver

spanSplenomegalySigns

of

decompensation

(jaundice,

ascites,asterixis)Slide

20DIAGNOSIS

OF

CIRRHOSIS

–

LABORATORYSTUDIESTests

that

explore

liver

synthetic

function

are

serumalbumin

and

prothrombintime,

while

serumbilirubin

investigates

the

ability

of

the

liver

to

conjugate

and

excretebilirubin.

Withliver

dysfunction

there

is

hypoalbuminemia,a

prolonged

prothrombin

time

and

hyperbilirubinemia

and

the

presence

of

either

of

these

findings,

in

thepresence

of

chronic

liver

disease,

indicates

the

possibility

of

cirrhosis.

However,

an

even

earlier

more

sensitive

finding

suggestive

of

cirrhosis

is

a

lowplatelet

countthat

occurs

as

a

result

of

portal

hypertension

and

hypersplenism.

An

AST/ALT

ratio

>1

has

also

been

identified

as

having

a

high

specificity

but

a

lowsensitivity,therefore

its

absence

cannot

exclude

cirrhosis.Poynard

and

Bedossa.

J

Viral

Hepat.

1997;

4:199Dienstag

JL,

Hepatology

2002;

36

(Suppl

1):

S152LaboratoryLiver

insufficiencyLow

albumin

(<

3.8

g/dL)Prolonged

prothrombin

time

(INR

>

1.3)High

bilirubin

(>

1.5

mg/dL)Portal

hypertensionLow

platelet

count

(<

175

x1000/ml)AST

/

ALT

ratio

>

1In

Whom

Should

We

Suspect

Cirrhosis?Slide

23DIAGNOSIS

OFCIRRHOSIS

–

CAT

SCANThis

slide

shows

typical

computed

tomography

findings

in

compensated

cirrhosis.

The

contourof

the

liver

is

irregular,

there

is

obvious

splenomegalyand

thepresence

of

collaterals

indicates

portal

hypertensionand

secures

the

diagnosis

of

cirrhosis.CT

Scan

in

CirrhosisLiver

with

an

irregular

surfaceSplenomegalyCollateralsSlide

41DIAGNOSTIC

ALGORITHMDiagnostic

algorithm

to

investigate

the

presence

of

cirrhosis

in

patients

withchronic

liver

disease.NoYesDiagnostic

AlgorithmPatient

with

chronic

liver

disease

and

any

ofthefollowing:Variceal

hemorrhageAscitesHepaticencephalopathyLiver

biopsy

notnecessary

forthediagnosis

of

cirrhosisPhysical

findings:Enlarged

left

hepatic

lobeSplenomegalyStigmataof

chronic

liver

diseaseLaboratory

findings:ThrombocytopeniaImpaired

hepatic

synthetic

functionRadiological

findings:Small

nodular

liverIntra-abdominal

collateralsAscitesSplenomegalyColloid

shift

to

spleen

and/or

bone

marrowYes

NoYes

NoLiver

biopsySlide

44MECHANISMS

OF

PORTAL

HYPERTENSIONIn

fluid

mechanics,

Ohm’s

law

states

that

pressure

(P)

is

dependent

upon

flow

(F)

and

resistance

to

flow

(R).

Therefore,

portal

hypertension

can

result

fromanincrease

in

portal

venous

inflow,

an

increase

in

resistance

to

portal

flow

or

an

increase

in

both

flow

and

resistance.Mechanisms

of

Portal

HypertensionPressure

(P)

results

from

the

interactioof

resistance

(R)

and

flow

(F):P

=

R

x

FPortal

hypertension

can

result

from:increase

in

resistance

to

portal

flowand/orincrease

in

portal

venous

inflowSlide

47THE

NORMAL

LIVER

OFFERS

ALMOST

NO

RESISTANCE

TO

FLOWThe

normal

liver

can

withstand

significant

increases

in

flow,

without

resulting

in

increases

in

portal

pressure.

The

normal

portal

venous

system

is

alow-pressuresystemand

vessels

draining

the

intraabdominal

organs,

such

as

the

coronaryvein,

drain

into

it.Normal

LiverHepaticveinSinusoidPortalveinLiverSplenicveinCoronaryveinSlide

48ARCHITECTURAL

LIVER

DISRUPTION

IS

THE

MAIN

MECHANISM

THAT

LEADS

TO

AN

INCREASED

INTRAHEPATIC

RESISTANCEThe

deposition

of

fibrous

tissue

and

the

formationof

nodules,

disrupts

the

architecture

of

the

liver,

leading

to

an

increased

resistance

to

flow

and

to

portalhypertension.

Vessels

that

normally

drain

into

the

portal

system,

such

as

the

coronary

vein,

reverse

their

flow

and

become

porto-systemic

collaterals.

Additionally,withportal

hypertension,

the

spleen

increases

in

size

and

sequesters

platelets

and

other

formed

blood

cells

leadingto

hypersplenism.PortalsystemiccollateralsDistortedsinusoidalarchitectureleads

toincreasedresistancePortalveinCirrhotic

LiverSplenomegalySlide

65AN

INCREASE

IN

PORTAL

VENOUS

INFLOW

SUSTAINS

PORTAL

HYPERTENSIONThe

initial

mechanismin

the

development

of

portal

hypertension

in

cirrhosis

is

an

increase

in

vascular

resistance

to

portal

flow

mostly

due

to

a

distorted

sinusoidalarchitecture.

However,

a

subsequent

increase

in

portal

venous

inflow

secondary

to

splanchnic

vasodilatation,

maintains

the

portal

hypertensive

state.MesentericveinsFlowSplanchnicvasodilatationDistortedsinusoidalarchitechurePortalveinAn

Increase

in

Portal

Venous

Inflow

SustainsPortal

Hypertension20Slide

82VARICES

INCREASE

IN

DIAMETER

PROGRESSIVELYBothdevelopmentof

varices

and

growth

of

small

varices

occurs

at

a

rate

of

7-8%

per

year.

Although

there

are

no

identified

clinical

predictors

for

the

developmentof

varices,

factors

associated

with

variceal

growth

are

Child

B/C

cirrhosis,

alcoholic

etiologyand

presence

of

red

wale

marks

on

initial

endoscopy.Merli

et

al.,

J

Hepatol

2003;

38:

266Small

varicesLarge

varicesNo

varices7-8%/year7-8%/yearVarices

Increase

in

DiameterProgressivelyMerli

et

al.

J

Hepatol

2003;38:266V

AR

ICES

I

NCREASE

IN

DIAMETER

PR

OGRESSIV

ELYSlide

85A

THRESHOLD

PORTAL

PRESSURE

OF

~12

mmHg

IS

NECESSARYFOR

VARICES

TO

FORMInitial

dilatation

of

the

esophageal

collaterals

depends

on

a

threshold

portal

pressure

below

which

varices

do

not

develop.

This

threshold

has

been

established

at

anhepatic

venous

pressure

gradient

(HVPG)

of

11-12

mmHg.

Notably,

patients

withno

varices

mayhave

an

HVPG

>12

mmHg.

Therefore

the

threshold

HVPG

levelis

necessary

but

not

sufficient

for

the

development

of

gastroesophageal

varices.

Factors

other

than

pressure,

such

as

volume

of

blood

flow

and

local

anatomic

factorsmay

contribute

to

the

formationof

varices.Garcia-Tsao

et

al.,

Hepatology

1985;

5:

419A

Threshold

Portal

Pressure

of

~12

mmHg

isNecessary

for

Varices

to

FormP<0.0115121025353020HepaticVenousPressureGradient(mmHg)5Garcia-Tsao

et.

al.,

Hepatology

1985;

5:419VaricesPresent(n=72)Varices

Absent(n=15)Slide

96PROGRESSION

OF

PORTAL

HYPERTENSION

LEADS

TO

VARICEAL

GROWTH

AND

VARICEAL

RUPTUREAs

flow

increases

through

gastroesophageal

varices,

they

grow

and

eventually

they

rupture,

leadingto

the

most

dreaded

complication

of

portal

hypertension,

varicealhemorrhage.VaricealrGurpotwutrhePortalpressureResistance

toportal

flowCirrhosisSplanchnicarteriolarresistancePortal

bloodinflowVaricesPR

OGR

ESSIO

N

OF

P

OR

TAL

HYP

ERT

EN

SI

ON

LEADS

T

O

V

ARI

CEAL

GROWT

H

AN

D

V

ARI

CEAL

R

UP

TUR

ESlide

97PROGNOSTIC

INDICATORS

OF

FIRST

VARICEAL

HEMORRHAGEIn

a

prospective

study,

the

presence

of

the

following

clinical

features

was

associated

with

a

high

probability

of

developing

variceal

hemorrhage:

large

variceal

size,Child

B/C

and

the

presence

of

red

wale

markings

on

varices.North

Italian

Endoscopic

Club.

N

Engl

J

Med

1988;

319:

983Predictors

of

hemorrhage:VaricealsizeRedsignsChild

B/CNIEC.

N

Engl

J

Med

1988;

319:983Variceal

hemorrhageVarix

with

red

signsSlide

99VARICEAL

WALL

TENSION

IS

A

MAJOR

DETERMINANT

OF

VARICEAL

RUPTURERuptureof

a

vessel

occurs

when

the

expanding

force

exceeds

its

maximal

wall

tension.

The

higher

the

tension,

the

greater

the

possibility

of

rupture.

Tension

in

the

varix

(T)

is

directly

proportional

to

transmural

pressure

(difference

between

the

intravariceal

and

the

intraluminalesophageal

pressure)

and

to

variceal

radius

(r)

and

isinversely

proportional

to

variceal

wall

thickness.

A

large

varix

hasalarge

radius

and

a

thin

wall

and

thereforea

larger

tension

and

agreater

propensity

to

rupture.Groszmann

RJ.

Gastroenterology

1984;

80:1611Tension

(T)Wall

thickness(w)Groszmann,

Gastroenterology

1984;

80:1611T

=

tp

xrwVariceal

Wall

Tension

(T)

is

a

MajorDeterminant

of

Variceal

RuptureTransmuralpressure

(tp)Radius(r)EsophagusVarixSlide

135MANAGEMENT

ALGORITHM

FOR

THE

PROPHYLAXIS

OF

VARICEAL

HEMORRHAGE

-SUMMARYProphylaxis

of

Variceal

HemorrhageDiagnosis

of

CirrhosisEndoscopyNo

VaricesFollow-up

EGD

in

2-3

years*Small

VaricesFollow-up

EGD

in

1-2

years*Medium/Large

VaricesStepwise

increase

until

maximally

tolerated

doseContinue

beta-blocker

(life-long)ContraindicationsorBeta-blocker

intolerancBeta-blocker

therapyNo

ContraindicationsEndoscopic

Variceal

Band

Ligation*EGD

every

year

in

decompensated

cirrhosisSlide

138TREATMENT

OF

ACUTE

VARICEAL

HEMORRHAGETreatment

of

acute

variceal

hemorrhage

includes

general

and

specific

therapies.

General

management

includes

establishing

intravenous

access

and

fluid

resuscitation.Vigorous

fluid

resuscitation

and

transfusion

to

hemoglobinlevels

>8

g/dL

should

be

avoided

as

this

could

precipitate

early

variceal

rebleeding.

Prophylactic

antibiotictherapy

should

be

instituted

promptly

in

any

cirrhotic

patient

with

gastrointestinalhemorrhage.

Specific

therapy

includes

pharmacologicaltherapy,

endoscopic

therapyand

shunt

therapy.Treatment

of

Acute

Variceal

HemorrhageGeneral

Management:IV

access

and

fluid

resuscitationDo

not

overtransfuse

(hemoglobin

~

8

g/dL)Antibiotic

prophylaxisSpecific

therapy:Pharmacological

therapy:

terlipressin,somatostatin

and

analogues,

vasopressin

+nitroglycerinEndoscopic

therapy:

ligation,

sclerotherapyShunt

therapy:

TIPS,

surgical

shuntSlide

144ENDOSCOPIC

VARICEAL

BANDLIGATIONEndoscopic

variceal

ligation

consists

of

the

placement

of

rubber

rings

on

variceal

columns

with

the

objective

of

interruptingblood

flow

and

subsequentlydevelopingnecrosis

of

mucosa

and

submucosa

and

replacement

of

varices

by

scar

tissue.

Endoscopic

therapy

is

a

local

therapy

that

has

no

effect

on

the

pathophysiologicmechanisms

that

lead

to

portal

hypertension

and

variceal

rupture.

Eventhough

it

achieves

variceal

obliteration,

varices

will

eventuallyrecur.

Bleedingis

controlled

in90%of

cases

of

acute

variceal

hemorrhage

with

a

rebleeding

rate

of

30%.

Meta-analysis

of

trials

comparing

ligationwith

sclerotherapy

has

shown

that

ligation

isassociated

with

lower

rebleeding

rates,

lower

number

of

sessions

to

achieve

variceal

obliteration

and

lower

mortality.

Complications

of

endoscopic

therapy

are

related

mainly

to

the

development

of

esophageal

ulcerationand

strictures,

significantly

more

frequent

after

sclerotherapy

than

after

ligation.Laineand

Cook.

Ann

Intern

Med

1995;

123:280Endoscopic

Variceal

Band

LigationBleeding

controlled

in

90%Rebleeding

rate

30%Compared

with

sclerotherapy:·

Less

rebleeding·

Lower

mortality·

Fewer

complications·

Fewer

treatment

sessionsSlide

147THE

TRANSJUGULAR

INTRAHEPATIC

PORTOSYSTEMIC

SHUNTPortal

hypertension

can

be

corrected

bycreatinga

communication

between

the

hypertensive

portal

systemand

low-pressure

systemic

veins,

bypassing

the

liver,

i.e.,the

site

of

increased

resistance.

This

communication

can

be

created

surgicallyor

by

the

transjugular

placementof

an

intrahepatic

stent

that

connects

a

branch

of

theportal

vein

witha

branch

of

an

hepatic

vein,

a

procedure

designated

transjugular

intrahepatic

porto-systemic

shunt

(TIPS).

TIPS

is

performed

by

advancing

a

catheter

introduced

through

the

jugular

vein

into

ahepatic

vein

and

into

a

main

branch

of

the

portal

vein.

An

expandable

stent

is

then

introduced

connecting

hepaticand

portal

systems,

and

blood

from

the

hypertensive

portal

vein

and

sinusoidal

bed

is

shunted

to

the

hepatic

vein.

The

procedure

is

highly

effective

in

correctingportal

hypertension

but

can

be

associated

with

complications

related

to

diversionof

blood

flow

away

from

the

liver,

namely

portal-systemic

encephalopathyand

liverfailure.Transjugular

Intrahepatic

Portosystemic

ShuntPortal

veinSplenicveinSuperior

mesentericveinHepaticveinTIPSSlide

158MANAGEMENT

ALGORITHM

IN

ACUTE

ESOPHAGEAL

VARICEALHEMORRHAGEManagement

of

Acute

Variceal

HemorrhageBalloon

TamponadeVariceal

Hemorrhage

SuspectedInitial

ManagementAcute

Hemorrhage

Controlled?NO

YESYES2nd

EndoscopyRescue

TIPS/Shunt

surgeryFurther

bleedingEarly

rebleeding?NOProphylaxis

against

recurrenthemorrhage30Slide

180SUMMARYOF

MANAGEMENT

OF

VARICES

AND

VARICEAL

HEMORRHAGEEvolution

ofVaricesLevel

ofInterventionManagement

RecommendationsCirrhosis

with

novaricesSmall

varicesNo

hemorrhageMedium

/

large

varicesNo

hemorrhageVariceal

hemorrhageRecurrent

varicealhemorrhagePre-primaryprophylaxisPrimaryprophylaxisSecondaryprophylaxisRepeat

endoscopy

in

2-3

yearsNo

specific

therapySmall

varicesRepeat

endoscopy

in

1-2

yearsNo

specific

therapy?

beta-blocker

toprevent

enlargementMedium/Large

varicesNon-selective

beta-blockersEVL

in

those

intolerant

to

drugsEndoscopic/pharmacologic

therapyAntibiotics

in

all

patientsTIPS

or

shunt

surgery

as

rescuetherapBeta-blockers

+

nitrates

orEVLBeta-blockers

+

EVL

?TIPS

or

shunt

surgery

as

rescuetherapSlide

203ASCITES

AND

HEPATORENAL

SYNDROMEThe

most

common

complication

of

cirrhosis

that

results

fromportal

hypertension

and

the

consequent

vasodilatationis

the

development

of

ascites

and,

in

its

extreme,the

developmentof

hepatorenal

syndrome.

The

next

section

will

deal

withthe

pathogenesis

and

managementof

these

complications.Ascites

and

Hepatorenal

SyndromeSlide

214PATHOGENESIS

OF

ASCITESCirrhosis

leads

to

hepatic

venous

outflowblock

which

is

bothanatomical

(fibrosis

and

regenerative

nodules)

and

functional

(increased

intrahepatic

vascular

tone

that,incirrhotic

rats

with

ascites,

is

predominantly

post-sinusoidal)

and

thereby

to

an

increased

sinusoidal

pressure.

In

addition,

portal

hypertension

leads

to

splanchnicand

systemic

arteriolar

vasodilation,

decreased

effective

arterial

blood

volume,

upregulation

of

sodium-retaining

hormones,

sodiumand

water

retentionandconsequently,

plasma

volume

expansion.

Sinusoidal

hypertension

drives

fluid

out

of

the

sinusoids

and

into

the

peritoneal

cavity

while

the

intravascular

fluid

iscontinuouslyreplenished

by

the

process

ofplasma

volume

expansion.CirrhosisActivation

ofneurohumoral

systems(renin,

angiotensin,aldosterone)Effectivearterial

bloodvolumeHepaticvenous

outflowblockAscitesSinusoidalpressure(HVPG

10-12

mmHg)Sodium

andwater

retentionArteriolarresistance(vasodilation)P

AT

HOG

ENESIS

OF

ASCIT

ESSlide

221ULTRASOUND

IS

THE

MOST

SENSITIVE

METHOD

TO

DETECT

ASCITESPhysical

examination

is

relativelyinsensitive

for

detecting

ascitic

fluid,

particularlywhenthe

amount

is

small

and/or

the

patient

is

obese.

The

initial,

most

cost

effectiveand

least

invasive

method

to

confirm

the

presence

of

ascites

is

abdominal

ultrasonography.

It

is

considered

the

gold

standard

for

diagnosingascites

as

it

can

detectamountsas

small

as

100

mL

and

even

as

small

as

1-2mLwhen

Morison’s

pouch

and

the

pelvic

cul-de-sac

are

scanned.

This

slide

shows

an

ultrasound

with

amoderate

amount

of

ascites.Ultrasound

is

the

Most

Sensitive

Method

toDetect

AscitesLiverAscitesSlide

222INITIAL

WORKUP

OF

ASCITES:

DIAGNOSIS

PARACENTESISFor