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CRISTINA

CIJEVSCHI PRELIPCEAN

CTLINA
MIHAI

NOIUNI DE
GASTROENTEROLOGIE
I HEPATOLOGIE
PENTRU STUDENI

Editura Gr. T. Popa" , U.M.F. Iai


2013

Descrierea CIP a Bibliotecii Naionale a Romniei


Cijevschi-Prelipcean, Cristina
Gastroenterologie i hepatologie pentru studeni / Cristina Cijevschi
Prelipcean, Ctlina Mihai. - Iai : Editura Gr.T. Popa, 2013
Bibliogr.
ISBN 978-606-544-133-0
616.3(075.8)

Refereni tiinifici:
Prof. Univ. Dr. Mircea DICULESCU, Universitatea de Medicin i Farmacie
Carol Davila Bucureti
Prof. Univ. Dr. Dan DUMITRACU, Universitatea de Medicin i Farmacie Iuliu
Haieganu Cluj Napoca

Editura Gr. T. Popa


Universitatea de Medicin i Farmacie Iai
Str. Universitii nr. 16

Toate drepturile asupra acestei lucrri aparin autorului i Editurii Gr.T. Popa" Iai. Nici o
parte din acest volum nu poate fi copiat sau transmis prin nici un mijloc, electronic sau
mecanic, inclusiv fotocopiere, fr permisiunea scris din partea autorului sau a editurii.

Tiparul executat la Tipografia Universitii de Medicin i Farmacie "Gr. T. Popa" Iai


str. Universitii nr. 16, cod. 700115, Tel. 0232 301678

Prefa
Hipocrate spunea c toate afeciunile au originea n tubul digestiv.
Cartea Noiuni de gastroenterologie i hepatologie pentru studeni a aprut
din necesitatea de a prezenta ntr-o manier succint cunotinele de baz din
gastroenterologie i hepatologie, noiuni pe care orice medic trebuie s le
cunoasc i aplice n practica clinic curent.
Aa cum sugereaz i titlul, cartea se adreseaz n primul rnd
studenilor Facultii de Medicin dar n acelai timp credem c va fi un
instrument apreciat de ctre medicii rezideni gastroenterologi i din alte
specialiti nrudite, doctoranzi i practicieni cu experien care doresc s i
actualizeze cunotinele n domeniu.
Din punct de vedere al coninutului lucrarea este structurat ntr-o
manier clasic, parcurgnd principalele afeciuni digestive, de la
epidemiologie la tratament. ntr-o specialitate n care progresele se deruleaz
rapid, am ncercat s integrm noiunile clasice cu cele mai noi achiziii
tiinifice, eliminnd elementele perimate i punnd accent pe noile modaliti
de diagnostic i tratament, n concordan cu ghidurile i recomandrile
actuale.
Spre deosebire de cursurile clasice, originalitatea este dat de formatul
crii: pe de o parte prezentarea schematic, succint, a noiunilor teoretice iar
pe de alt parte spaiile libere alturate care permit cititorului s fac adnotri,
completri, precizri, facilitnd procesul de cunoatere.
Editarea acestei cri nu a fost o munc uoar. Mulumim
colaboratoarelor noastre dr. Mihaela Dranga i dr. Iulia Pintilie pentru
ajutorul dat n tehnoredactare. Din punctul nostru de vedere cartea a fost un
exerciiu, n care am regsit ceea ce spunea Seneca: nvei nvnd pe alii.
Sperm ca i din punct de vedere al cititorilor cartea s fie un instrument util n
formarea medical.
Cristina Cijevschi Prelipcean
Ctlina Mihai

ABREVIERI
5 ASA: 5 aminosalicilic

CP: cancer pancreatic

Ac: anticorpi

CRP: protein C reactiv

ACE: antigen carcinoembrionar

CT: computer tomografie

AFP: alfafetoprotein

DAA: antivirale cu aciune direct

Ag: antigen

DZ: diabet zaharat

AINS: antiinflamatorii nesteroidiene

EB: esofag Barrett

ALT: alaninaminotransferaza

EDS: endoscopie digestiv superioar

ANA: anticorpi antinucleari

EEG: electroencefalogram

ASMA: anticorpi anti fibr muscular


neted

EHP: encefalopatie hepato-portal

AST: aspartataminotransferaza

ERCP: colangiopancreatografie retrograd


endoscopic

AZT: azatioprin

EUS: ultrasonografie endoscopic

BC: boal Crohn

FA: fosfataza alcalin

BII: boal inflamatorie intestinal

FAP: polipoza adenomatoas familial

BRGE: boal de reflux gastroesofagian

FOBT: hemoragii oculte fecale

CBIH: ci biliare intrahepatice

FR: factor reumatoid

CBP: ciroz biliar primitiv

GGTP: gamaglutamiltranspeptidaza

CCR: cancer colorectal

HAI: hepatit autoimun

CE: cancer esofagian

HCC: hepatocarcinom

CG: cancer gastric

HDS: hemoragie digestiv superioar

CH: ciroz hepatic

HIV: virusul imundeficienei umane

COX: ciclooxigenaz

HNPCC: cancer colorectal ereditar


nonpolipozic

Hp: Helicobacter pylori

PMN: polimorfonucleare

HRM: manometrie de nalt rezoluie

PR: poliartrit reumatoid

HTA: hipertensiune arterial

Ps: prednison

HTP: hipertensiune portal

RBV: ribavirin

IFN: interferon

RCUH: rectocolit ulcero-hemoragic

Il: interleukin

RM: rezonan magnetic

IPP: inhibitori de pomp de protoni

RVS: rspuns viral susinut

IRC: insuficien renal cronic

SDE: spasm difuz esofagian

IS: intestin subire

SEI: sfincter esofagian inferior

LDH: lacticdehidrogenaza

SES: sfincter esofagian superior

LES: lupus eritematos sistemic

TA: tensiune arterial

MALT: esut limfatic asociat mucoasei

TIPS: unt portosistemic intrahepatic


transjugular

MRCP: colangiopancreatografie prin


rezonan magnetic

Tis: tumor in situ

MTS: metastaze

TNF: factor de necroz tumoral

NAFLD: ficat gras nonalcoolic

UD: ulcer duodenal

NASH: steatohepatit nonalcoolic

UG: ulcer gastric

NO: oxid nitric

VE: varice esofagiene

PA: pancreatita acut

VHA: virusul hepatitic A

PAF: factor activator plachetar

VHB: virusul hepatitic B

PBH: puncie biopsie hepatic

VHC: virusul hepatitic C

PBS: peritonit bacterian spontan

VHD: virusul hepatitic D

PC: pancreatit cronic

VIP: peptidul intestinal vasoactiv

PCR: reacie de polimerizare n lan

VP: vena port

PET: tomografie cu emisie de pozitroni

VS: vena splenic

CUPRINS
METODE DE EXPLORARE A TRACTULUI DIGESTIV ............................ 1
DISPEPSIA .................................................................................... 15
HELICOBACTER PYLORI DUP MASTRICHT IV ................................ 21
BOALA DE REFLUX ESOFAGIAN ..................................................... 29
TULBURRI MOTORII ESOFAGIENE ............................................... 41
CANCERUL ESOFAGIAN ................................................................ 49
ULCERUL GASTRIC I DUODENAL .................................................. 53
CANCERUL GASTRIC ..................................................................... 71
PATOLOGIA INTESTINULUI SUBIRE.............................................. 85
COLONUL IRITABIL ....................................................................... 97
BOLILE INFLAMATORII INTESTINALE ............................................105
CANCERUL COLORECTAL .............................................................125
HEPATITA CRONIC VIRAL C ......................................................137
HEPATITA CRONIC VIRAL B......................................................145
FICATUL GRAS NONALCOOLIC .....................................................155
BOALA HEPATIC ALCOOLIC ......................................................161
HEPATITELE AUTOIMUNE ............................................................167
CIROZA HEPATIC .......................................................................173

CANCERUL HEPATIC PRIMITIV .....................................................207


PATOLOGIA BILIAR....................................................................215
PANCREATITA ACUT ..................................................................229
PANCREATITA CRONIC ..............................................................239
CANCERUL PANCREATIC ..............................................................249
BIBLIOGRAFIE SELECTIV ............................................................255

METODE DE EXPLORARE A
TRACTULUI DIGESTIV
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Introducere

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Hipocrate: All the diseases begin in the gut


Afeciunile digestive intereseaz un segment important
din populaia general, indiferent de vrst, mai ales
persoane de vrst medie
Costuri directe: spitalizare, investigaii, tratamente
Costuri indirecte: absenteism, pensionare, asisten la
domiciliu, moarte prematur
Afeciunile funcionale (dispepsie, reflux gastroesofagian, colon iritabil): What matters in chronic
disorders is the patients suffering, not the disease entity

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ENDOSCOPIA DIGESTIV SUPERIOAR

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Primul endoscop optic flexibil a fost realizat de Hirschowitz


i colaboratorii

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Este metod diagnostic i terapeutic

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ERCP colangiopancreatografie endoscopic retrograd

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EUS ultrasonografie endoscopic

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n ultimii ani progrese n acurateea diagnosticului prin


cromoendoscopie, magnificaie, narrow band imaging

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Indicaii:
simptomatologie dispeptic la persoane n vrst sau cu
simptome de alarm (hemoragie gastrointestinal,
scdere ponderal, vrsturi sugernd insuficien
evacuatorie gastric, anemie etc. ) sau rebel la
tratament
disfagie
ingestie de corpi strini, substane caustice
hemoragie digestiv superioar (acut i cronic)
durere abdominal cronic
boal inflamatorie intestinal (boal Crohn)
suspiciune de neoplazie
confirmare examen radiologic
supraveghere leziuni preneoplazice

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Contraindicaii:
refuzul pacientului
pacient necooperant, agitat
suspiciune de perforaie intestinal
pacient n stare de oc (EDS se va efectua dup
echilibrare volemic)
afeciuni severe asociate (infarct de miocard
recent, accident vascular cerebral)

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! Consimmnt informat

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Pregtirea pacientului:
repaus alimentar de cel puin 6 ore
n urgen (HDS) splturi gastrice anterior
explorrii
anestezie topic faringian xilin
decubit lateral stng
sedare iv midazolam 2-5 mg

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Endoscopia digestiv superioar terapeutic


- HDS variceal: sclerozare endoscopic prin injectare de
substane sclerozante (moruat de sodiu, alcool absolut etc)
sau ligatur variceal cu benzi elastice
HDS non variceal: hemostaz prin injectare de
epinefrin sau soluie salin hiperton, fotocoagulare laser,
electrocoagulare, termocoagulare, clipare

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dilatare stenoze: esofagiene, pilorice

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extragere corpi strini

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proteze

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polipectomii

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mucosectomie endoscopic

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tratament endoscopic n BRGE, acalazia cardiei

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Complicaii:
majore la 1/1000 - 1/3000 de endoscopii
perforaii ale esofagului, stomacului
hemoragie
aspiraie pulmonar (mai frecvent la EDS cu sedare)
aritmii cardiace severe

mortalitatea variaz ntre 1/3000 i 1/16000 de endoscopii

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sedarea cu midazolam reacii alergice, hipotensiune,


depresie respiratorie

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Endoscopia digestiv inferioar

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Indicaii:

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sngerare digestiv (rectoragie sau sngerare ocult)

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boal inflamatorie intestinal

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suspiciune de polipi, cancer

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durere abdominal cu etiologie neprecizat

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tulburri de tranzit intestinal

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Contraindicaii:

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aceleai ca la endoscopie +

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boal inflamatorie intestinal fulminant

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megacolon toxic

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Pregtire:
- Evacuarea colonului (fortrans, picoprep, clisme
evacuatorii)

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Posibilitate de efectuare cu sedare

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Endoscopia digestiv inferioar terapeutic:


polipectomii
mucosectomie
tratament hemostatic (injectare de substane
vasoconstrictoare, fotocoagulare, clipuri etc)
dilatare stenoze
stenturi

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Complicaii
Complicaii majore
Perforaia
Hemoragia
< 1% din colonoscopii, mai frecvent n cele terapeutice
(polipectomii)
Alte complicaii
Aritmii cardiace
Reacii vasovagale
Hipotensiune, insuficien cardiac (pregtire
colonoscopie)
Reacii la medicamentele folosite pentru sedare

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Colangiopancreatografia endoscopic
retrograd - ERCP

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Vizualizarea cilor biliare i canalului pancreatic

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Invaziv (risc de pancreatit acut!) n scop diagnostic


metoda a fost nlocuit de tehnici noninvazive (MRCP)

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i pstreaz valoarea i utilitatea ca metod terapeutic:

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- sfincterotomie endoscopic extracie de calculi

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- stentare endoscopic

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Enteroscopia

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Vizualizarea intestinului subire

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Rol diagnostic (inclusiv prelevare de biopsie) i terapeutic


(hemostaz, polipectomii)
Eficien diagnostic comparabil cu videocapsula

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Tehnici: spiral, dublu balon etc

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Metod laborioas, necesit sedare, dotare i endoscopist


cu experien

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CAPSULA ENDOSCOPIC

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1966, Fantastic Voyage (Raquel Welch) submarin


miniaturizat aruncat n circulaia sanguin

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Ideal o singur capsul pentru explorarea complet a


tractului digestiv, de la cavitatea oral la anus

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n prezent capsul IS, esofag, colon

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Metod
Pacient a jun de cel puin 8 ore
Ingerare capsul cu un pahar cu ap
interzis fumatul modific culoarea mucoasei
gastrice
nu se administrez:
antiacide ader la mucoas mpiedic
vizualizarea
antispastice ncetinesc tranzitul intestinal
sucralfat
preparate de fier
narcotice
La 2 ore de la ingestie sunt permise lichidele, la 4 ore
o gustare

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Indicaii

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- boala Crohn
- hemoragia gastrointestinal de cauz obscur

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Indicaii relative
- boala celiac
- suspiciunea unei tumori maligne de intestin subire
- polipoza intestinal ereditar (sindromul PeutzJeghers, polipoz juvenil familial)
- leziunile vasculare intestinale
- enteropatia indus de AINS
- diareea cronic
- durerea abdominal (suspiciune de boal
organic)
- transplantul de intestin subire (diagnosticul
rejetului de gref)

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Contraindicaii
Stenoz, obstrucie, fistul (orice segment al tractului
gastrointestinal)
Intervenii chirurgicale majore anterioare
abdominale/pelvine
Tulburri de deglutiie
Pseudo-obstrucie intestinal
Pacemaker cardiac sau alt dispozitiv electromedical
implantat
Contraindicaii relative: sarcin, diverticul Zenker,
gastroparez, diverticuloz intestinal (diverticuli
numeroi i voluminoi)

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Complicaii
1. Impactarea capsulei la nivelul unei stenoze
intestinale nediagnosticate anterior
2. Aspiraia traheal a capsulei
3. Impactarea capsulei la nivel cricofaringian
4. Retenia capsulei n diverticul Zenker

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Ideal n suspiciunea de stenoz sau alte leziuni


obstructive se administraz capsula de paten
biodegradabil!

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Concluzii

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capsula endoscopic s-a impus ca cea mai performant


metod de examinare a intestinului subire

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reprezint metoda de elecie n diagnosticul bolii Crohn


i pentru stabilirea etiologiei hemoragiei digestive de
cauz obscur

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este metod sigur, practic lipsit de complicaii dac se


face selecia adecvat a pacienilor

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dezavantajele sunt legate de pre, imposibilitatea de a


preleva biopsii i de a efectua manevre terapeutice

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Viitor capsul ideal?

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o singur capsul pentru ntreg tractul digestiv


examinare inclusiv ultrasonografic
msurarea pH-ului, temperaturii, presiunii
aprecierea eliberrii medicamentelor la diferite nivele
determinarea motilitii
prelevare de biopsii
detectare: markeri oncologici (ACE, CA19-9), markeri
serologici ( Ac anti edomisium), citokine etc.

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EXAMENUL RADIOLOGIC

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Radiografia abdominal simpl: perforaie, ocluzie,


calcificri
Radiografia baritat eso-gastro-duodenal
Tranzit intestin subire

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- specificitate, sensibilitate reduse


- enteroclisma
Clisma baritat (irigografia)
Colecistografia oral sau intravenoas nlocuite
de tehnici mai performante

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Ecografia abdominal

Accesibil
Ieftin
Neinvaziv
Repetabil
Diagnostic pozitiv, diagnostic diferenial, supraveghere,
puncii ecoghidate diagnostice i terapeutice
Ficat, colecist, pancreas, splin, rinichi, pelvis, tub
digestiv, cavitate peritoneal, vase
Ecografie Doppler vascularizaie, flux vascular
Ecografie cu substan de contrast caracterizarea
vascular a formaiunilor expansive, traumatismelor etc
Ecoendoscopia profunzimea invaziei tumorale a
tubului digestiv, diagnosticul etiologic al icterului
obstructiv, permite manevre terapeutice (drenare
pseudochisturi pancreas etc)

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Computer tomografia

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Rezoluie superioar ecografiei


Difereniaz formaiunile solide de cele chistice
Permite puncia cu ac fin (diagnostic), drenarea chisturilor
suprainfectate, abceselor (terapeutic)

Rezonana magnetic

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Avantaje (comparativ cu CT): nu utilizeaz radiaii


ionizante, nu necesit substan de contrast, nltur
artefactele osoase
Explorare hepatic (formaiuni expansive hepatice,
suprancrcare cu fier, tromboz portal)
Colangiografia RMN (MRCP) a nlocuit ERCP-ul
diagnostic

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Tomografia cu emisie de pozitroni

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Are avantajul evalurii nu doar structurale, ci i funcionale;


rol n detectarea recidivelor neoplazice la distan

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Puncia biopsie hepatic

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Indicaii:
Evaluarea inflamaiei, steatozei i fibrozei n hepatitele cronice
virale, cu implicaii terapeutice i prognostice
Formaiuni expansive hepatice (ecoghidat)
Diagnosticul bolilor colestatice, granulomatozelor hepatice
Post-transplant hepatic n cazul rejetului de gref

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Contraindicaii:
Timp de protrombin crescut, INR > 1.6
Trombocitopenie < 60.000/mmc
Ascit (se prefer calea transjugular)
Hemangioame hepatice
Suspiciune de chist hidatic
Pacient necooperant

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Complicaii

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Durere (pleural, peritoneal, diafragmatic)


Hemoragie (peritoneal, intrahepatic, hemobilie)
Peritonit biliar
Bacteriemie, sepsis
Pneumotorax, pleurezie, hemotorax
Emfizem subcutanat
Complicaii legate de anestezie
Biopsierea altor organe (rinichi, plmn, colon, colecist)
Mortalitate (0.0088-0.3%)

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Metode imagistice non-invazive de


evaluare a fibrozei hepatice
tind s nlocuieasc puncia biopsie hepatic (PBH) metod
invaziv n evaluarea pacienilor cu hepatopatii cronice
au o bun discriminare pentru fibroza joas (F0 F1) i
fibroza avansat (F4); sunt mai puin eficace n evaluarea
gradelor intermediare de fibroz

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cele mai multe studii au fost efectuate la pacieni cu hepatit


cronic viral C

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includ:
- elastografia n timp real HiRTE sau ARFI
- elastografia tranzitorie Fibroscan-ul
- elastografia prin rezonan magnetic

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Elastografia n timp real

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Poate fi efectuat:
- aparat Hitachi Hitachi Real Time Tissue
Elastography (Hi RTE) evalueaz relativ elasticitatea
hepatic printr-o scal de culori: cu ct esutul hepatic
este mai dur va predomina culoarea albastr
- aparat Siemens Acoustic Radiation Force Impulse
(ARFI) elasticitatea tisular este cuantificat ntr-o arie
predefinit fiind exprimat n m/s
Aceste dou metode au avantajul determinrii elasticitii
tisulare n continuarea unei ecografii standard
Necesit n continuare studii pentru validare n practica
clinic curent

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Elastografia tranzitorie (Fibroscan)

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este cea mai utilizat i validat modalitate de evaluare


non-invaziv a fibrozei hepatice
transducerul aparatului transmite vibraii de frecven i
amplitudine joas care vor fi reflectate de esutul hepatic
viteza undelor se coreleaz cu duritatea esutului
hepatic, iar rezultatele se exprim n kilopascali
pentru diagnosticul de ciroz hepatic (F4) sensibilitatea
i specificitatea Fibroscan-ului se apropie de 90%
n cazul activitii hepatice (transaminaze mult crescute)
rezultatele pot fi mai mari dect valoarea real a fibrozei
limitele metodei: pacienii cu obezitate morbid
(examinare cu sond special), ascit sau cu spaii
intercostale nguste

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Elastografia RMN

_____________________________________
_____________________________________

folosete unde mecanice de frecven joas realiznd o


hart a elasticitii i vscozitii hepatice

_____________________________________
_____________________________________

este o metod promitoare dar limitat nc de costul


crescut i accesibilitatea redus

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Metode serologice de apreciere a


fibrozei hepatice

_____________________________________
_____________________________________

Combin markeri serologici n vederea determinrii


fibrozei, activitii necro-inflamatorii i steatozei hepatice

_____________________________________
_____________________________________

La fel ca metodele imagistice au specificitate crescut


pentru absena fibrozei (F0) i fibroza avansat (F4); au
valoare redus n discriminarea gradelor intermediare de
fibroz

_____________________________________
_____________________________________
_____________________________________

Au valoare predictiv pentru evoluia i prognosticul bolii


hepatice

_____________________________________

APRI (raport AST/trombocite), Fibrotest, FibroMax

_____________________________________

_____________________________________

_____________________________________
_____________________________________

10

_____________________________________

Fibrotest/Actitest

_____________________________________

Fibrotest: alfa2macroglobulina, haptoglobina,


apolipoproteina A1, bilirubina total,
gamaglutamiltranspeptidaza

_____________________________________
_____________________________________
_____________________________________

Actitest asociaz ALT pentru determinarea activitii bolii


hepatice

_____________________________________
_____________________________________

Algoritmul ajusteaz rezultatele funcie de vrst i sex

_____________________________________
_____________________________________

Limite: hepatita acut (cresc valorile ALT), hemoliza acut


(scade valoarea haptoglobinei), stri inflamatorii acute
(crete valorea alfa2-macroglobulinei) sau sindrom Gilbert,
colestaza extrahepatica, hemoliz cronic (crete valoarea
bilirubinei)

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

FibroMax

_____________________________________
_____________________________________

Combinatie de 5 teste non-invazive diferite: FibroTest,


ActiTest, SteatoTest, NashTest i AshTest

_____________________________________
_____________________________________

Markeri serici: alfa-2macroglobulina, haptoglobina,


apolipoproteina A1, bilirubina total,
gamaglutamiltranspeptidaza, ALT, AST, glicemia bazal,
colesterolul, trigliceridele, ajustate funcie de vrsta,
sexul, greutatea i nlimea pacientului

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Limitele metodei: la fel ca pentru fibrotest/actitest

_____________________________________
_____________________________________
_____________________________________

FibroMax

_____________________________________

FibroTest msoara gradul fibrozei (corespunzator stadiilor


F0-F4 ale scorului METAVIR)
F0 absena fibrozei
F1 fibroz portal
F2 fibroz n punte cu rare septuri
F3 fibroz n punte cu numeroase septuri
F4 ciroz

_____________________________________

ActiTest msoara gradul de activitate necro-inflamatorie


(corespunzator gradelor A0-A3 ale scorului METAVIR)
A0 absena activitii
A1 activitate minim
A2 activitate moderat
A3 activitate sever

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

11

FibroMax

_____________________________________

SteatoTest evalueaz steatoza hepatic


0 absenta steatozei
S1 steatoz minim (<5% din hepatocite cu steatoz)
S2 steatoz moderat (6-32% din hepatocite cu steatoz)
S3 steatoz sever (33-100% din hepatocite cu steatoz)
NashTest evalueaz prezena steatohepatitei non-alcoolice la
pacieni obezi, cu dislipidemie, rezisten la insulin sau
diabet
N0 fr steatohepatit non-alcoolic
N1 steatohepatit non-alcoolic de grani
N2 steatohepatit non-alcoolic prezent
AshTest msoar gradul afectrii hepatice la pacienii cu
consum excesiv de etanol
H0 fr steatohepatit alcoolic
H1 steatohepatit alcoolic minim
H2 steatohepatit alcoolic moderat
H3 steatohepatit alcoolic sever

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Manometria

_____________________________________

Indicaii:
- tulburri motorii esofagiene
- durere toracic non-cardiac
- BRGE sever, pentru evaluarea peristalticii i a SEI

_____________________________________
_____________________________________
_____________________________________

Manometria de nalt rezoluie asociat cu graficul


topografic al presiunilor rol prognostic i n abordarea
terapeutic a tulburrilor motorii esofagiene
Manometria sfincterului Oddi diagnosticul diskineziilor
sfincteriene

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Teste de explorare n BRGE

_____________________________________

pH metria: monitorizare pH-ului esofagian n 24 ore

_____________________________________
_____________________________________

Bilitech
- aprecierea refluxului alcalin
- colecistectomizai, stomac operat

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Impedana esofagian: diferentierea refluxului n


funcie de consisten (solid, lichid etc)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

12

Alte explorri

_____________________________________

Teste respiratorii: infecia Hp, insuficiena pancreatic


exocrin, malabsorpia
Angiografia
- diagnosticul tumorilor abdominale
- poate evidenia sursa sngerrii
- valene terapeutice: vasopresin, chemoembolizare
Scintigrafia
- hepato-splenic nlocuit de ecografie, CT
- HIDA (acid dimetilfenilcarbamilmetil iminodiacetic)
evaluare colecist, ci biliare
- hematii marcate evidenierea sngerrii
- leucocite marcate evidenierea abceselor, necrozelor
tisulare

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

13

14

DISPEPSIA
_____________________________________
_____________________________________

Definiie

_____________________________________
_____________________________________

dys e peptein - nu se diger bine


Dispepsia - conglomerat de simptome cu sau fr substrat
organic n care durerea cronic sau recurent, localizat n
abdomenul superior este elementul principal

Durerea poate fi singurul element care caracterizeaz


dispepsia sau poate fi asociat cu:saietate precoce,
plenitudine postprandial, grea, vrsturi, eructaii, pirozis

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Epidemiologie

_____________________________________
_____________________________________

ntre 25-40% din populaia adult din rile industrializate


sufer de dispepsie recurent

_____________________________________

Reprezint 5-7% din totalul consultaiilor primare

_____________________________________

_____________________________________

_____________________________________

1% din EDS anuale se efectueaz pentru dispepsie

_____________________________________
_____________________________________

Prin costuri directe i indirecte, dispepsia depete n


multe ri SUA - 2 miliarde de dolari anual

_____________________________________
_____________________________________
_____________________________________
_____________________________________

15

_____________________________________

Clasificare i etiologie

_____________________________________

Dispepsia: A. Organic - 40% din cazuri


B. Funcional - 60% din cazuri

_____________________________________
_____________________________________

A.

Cauzele dispepsiei organice:

_____________________________________

I. Afeciuni organice ale tractului gastrointestinal:


refluxul gastroesofagian, gastropareza (diabet,
postvagotomie), neoplasmul gastric sau esofagian,
malabsorbia (boala celiac, intolerana la lactoz), ulcerul
peptic, patologia vascular ischemic, parazitoze (Giardia,
Strongyloides stercoralis)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

II. Medicamente : aspirina, antiinflamatorii

_____________________________________

nesteroidiene (AINS), antibiotice (macrolidele,


metronidazolul, sulfonamidele) , teofilina, digoxinul,
diuretice de ans, fierul, suplimentele de potasiu,
inhibitorii enzimei de conversie, estrogenii

_____________________________________
_____________________________________
_____________________________________
_____________________________________

III. Afeciunile biliopancreatice: pancreatita

_____________________________________

cronic, neoplasmul pancreatic, litiaza biliar,


diskineziile sfincterului Oddi

_____________________________________
_____________________________________

IV. Afeciunile sistemice : diabetul zaharat,

_____________________________________

afeciunile tiroidei, ischemia cardiac, insuficiena


cardiac congestiv, insuficiena renal, boli de
colagen etc

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

B. Dispepsia funcional

_____________________________________

problem de sntate public: prevalen n cretere


morbiditate ridicat
costuri socioeconomice semnificative

_____________________________________
_____________________________________
_____________________________________

Definiie (Roma III): prezena simptomelor dispeptice ( saietate


precoce, plenitudine postprandial, durere sau arsur epigastric cu
topografie abdominal) n absena leziunilor organice

Se caracterizeaz prin triada :


1. simptome persistente sau recurente (durere sau discomfort n
abdomenul superior)
2. absena unei afeciuni organice (inclusiv prin explorare
endoscopic)
3. nu se poate evidenia ameliorarea simptomelor dup defecaie
sau existena concomitent a modificrilor n numrul sau
consistena scaunelor

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

16

Roma I i Roma II: dispepsia durere i discomfort n


abdomenul superior
Roma III pstreaz definiia i adaug simptomele
cardinale ale dispepsiei:
durere epigastric
arsur epigastric
plenitudine postprandial
saietate precoce

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Dou sindroame noi majore Roma III


1. Postprandial dystress syndrome saietate precoce
postprandial, plenitudine postprandial
2. Epigastric pain syndrome durere sau arsur intermitente,
localizate n epigastru, cu intensitate variabil (moderat
sever) care apare cel puin o dat pe sptmn

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Fiziopatologie

_____________________________________
_____________________________________

tulburri de motilitate gastroduodenal


ntrzierea golirii gastrice
alterarea acomodrii gastrice
anomalii mioelectrice

_____________________________________
_____________________________________
_____________________________________
_____________________________________

hipersensibilitate visceral: fr cauz cunoscut,


fr legtur evident cu tulburrile de motilitate

_____________________________________
_____________________________________

relaia cu infecia cu Helicobacter pylori: n prezent nu


poate fi explicat prin consens

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tulburri de motilitate gastroduodenal

1) ntrzierea golirii gastrice


lipsa coordonrii eficiente a sistemului neuromuscular
gastric fa de bolul alimentar (40% din cazurile de
dispepsie) ar putea explica saietatea precoce
2) alterarea acomodrii gastrice
controlat normal prin vag i mediat prin eliberare de
oxid nitric i 5-OH triptamin
n dispepsia funcional bolul alimentar este distribuit
direct n stomacul distal determinnd dilataia brusc
antral
3) anomaliile mioelectrice
hipomotilitate antral postprandial ca urmare a
distensiei precipitate antrale

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

17

_____________________________________

Diagnostic pozitiv ( 1- 4)

_____________________________________

Anamneza esenial n afirmarea diagnosticului


Important de urmrit urmtoarele etape

_____________________________________
_____________________________________

1) simptomele de alarm
- scderea ponderal
- vrsturile incoercibile
- HDS (hematemez, melen)
- sindromul anemic
- disfagia
- icterul

necesit imediat investigaii


invazive pentru excluderea:
- leziunilor organice
- altor afeciuni (DZ,
afeciuni tiroidiene, cardiace)
afectare tiroidian, afeciune

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

+
- examen baritat cu
suspiciuni de diagnostic
- mas abdominal

_____________________________________
_____________________________________
_____________________________________

_____________________________________

2) explorarea umoral biochimic de rutin


- nu aduce date n susinerea diagnostic
3) endoscopia digestiv superioar ( gold standardul)
- exclude alte leziuni, confirm diagnosticul pozitiv
- imposibil de a efectua EDS la toi pacienii dispeptici
4) n cazuri selecionate pentru excluderea altor afeciuni:
- EDS cu biopsie duodenal (excludere boala celiac)
- echografie abdominal, eventual CT
- explorarea endoscopic, radiologic sau prin
videocapsul a intestinului subire
- pH-metrie esofagian - 24 ore, manometrie esofagian
- examen psihologic (stress prelungit, suprasolicitare,
tulburri psihiatrice cu fixaii cenestopate)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Diagnostic diferenial

_____________________________________
_____________________________________

1) refluxul gastro- esofagian (arsuri retrosternale,


regurgitaii acide)
important de difereniat ntruct are terapie diferit

_____________________________________
_____________________________________
_____________________________________

2) colonul iritabil
- asociaz n 50 % din cazuri simptomatologie
dispeptic

_____________________________________
_____________________________________

3) toate afeciunile organice care se nsoesc de sindrom


dispeptic

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

18

_____________________________________

Principii de tratament

_____________________________________
_____________________________________

Regimul igienodietetic

_____________________________________

- prnzuri mici, frecvente cu evitarea alimentelor care


agraveaz simptomatologia dispeptic
- evitarea grsimilor concentrate (lipidele ajunse n
duoden cresc sensitivitatea mecanic a stomacului)
- se contraindic formal cafeaua, alimentele picante
etc., n special seara (relaxare SEI)
- scderea n greutate
- ntreruperea fumatului

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________

Tratamentul medicamentos (1 5)

eradicarea Hp
tratament antisecretor
medicamente cu efecte asupra activitii motorii i reflexe
medicamente cu efect antinociceptiv
terapii alternative

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

1. Eradicarea Hp
- eradicarea Hp are, comparativ cu tratamentul
antisecretor, efect benefic mic
- singurul argument (cercettori japonezi ) pentru care se
indic eradicarea Hp este legat de profilaxia ulcerului
peptic i a cancerului gastric noncardial
2. Medicaia antisecretoare
- este superioar tratamentului de eradicare Hp n
dispepsie
- durata tratamentului este de 2-8 sptmni
- aciunea benefic se bazeaz pe diminuarea aciditii
i sensibilitii duodenale
- IPP > inhibitorii H2 > placebo
- beneficii > ca prim linie de tratament n epigastric
pain syndrome comparativ cu postprandial dystress
syndrome

19

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

3. Medicamente cu efect asupra activitii motorii i reflexe

_____________________________________

Medicaia prokinetic (stimuleaz musculatura neted


gastric)
acioneaz pe receptorii dopaminei (metoclopramida,
domperidonul)
accelereaz golirea gastric
stimuleaz contracia musculaturii nedete gastrice

_____________________________________

Eritromicina
macrolid, agonist al receptorilor motilinici

_____________________________________

_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tegaserod
agonist al receptorului 5 hidroxitriptaminic
administrat 6 mg x 2/zi accelereaz evacuare gastric
pe voluntarii sntoi i la pacienii cu dispepsie
Levosulpiride
antagonist dopaminergic cu efecte favorabile n special
n dispepsia prin dismotilitate

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

4. Medicamente cu efect antinociceptiv


Antidepresivele triciclice
n doze mici amelioreaz simptomele fr a
aciona pe senzaia de distensie gastric
antidepresivele n doze mici > placebo
Alte medicamente, cu efect analgezic visceral
agonitii opioizi
octreotridul
antagonitii neurokininei
5. Terapii alternative
hipnoza, relaxarea interpersonal i alte metode
psihiatrice: pe loturi mici, efect mai bun comparativ cu
placebo
medicaie naturist : experien favorabil pe loturi
mici

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________

Recomandrile Societii Americane de


Gastroenterologie n evaluarea dispepsiei:

_____________________________________
_____________________________________

Au la baz strategia test and treat


Primul pas testarea prezenei infeciei cu Hp
Dac este prezent se trateaz infecia Hp
n cazurile Hp negative se administreaz antisecretorii
sau prokinetice sau ambele
Pacienii care rmn simptomatici dup tratament - EDS

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

20

HELICOBACTER PYLORI
DUP MASTRICHT IV
_____________________________________
_____________________________________

Helicobacter pylori

_____________________________________

Bacterie dublu spiralat gram negativ


Activitate ureazic
50% din populaia adult infectat
Transmitere: oral- oral, fecal oral
Omul rezervor Hp; apa
Starea socio-economic a societii:
- ri n curs de dezvoltare 80-90% din populaia >20 ani
- ri dezvoltate 20% la persoanele >25 ani
- prevalena crete cu 1%/an 50 60% la 70 ani

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Istoric

_____________________________________
_____________________________________

1938 Doenges bacili curbiformi n mucoasa gastric

_____________________________________

1975 Sterr i Colin Jones - asociere cu gastrita

_____________________________________

1983 Warren i Marshall - descriere, rol n gastrit i


ulcer peptic - 2005 Premiul Nobel pentru medicin

_____________________________________

1987 European Helicobacter pylori Study Group (EHSG)


1996, 2000, 2005, 2012 Maastricht 1, 2, 3, 4

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

21

Testarea Helicobacter pylori

_____________________________________
_____________________________________

Teste noninvazive:
- confirm primo-infecia

_____________________________________

- verific succesul tratamentului

_____________________________________

Testul respirator C13 sau C14: ureaza Hp hidrolizeaz ureea


n bicarbonat i amoniu i elibereaza CO2 care este absorbit
i eliberat n plmn; specificitate 95%

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Ag n scaun
- de prim intenie la persoane < 45 ani, cu sindrom dispeptic,
dar fr semne de alarm sau istoric de cancer familial
- reduce numrul de endoscopii
- specificitate 98%

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________

Serologia

_____________________________________

- la pacienii netratai specificitate 90%


- nu poate fi folosit n verificarea succesului terapiei sau
n reinfecie (Ac rmn la valori crescute > 3 ani)

_____________________________________

- nu necesit oprirea IPP cu 2 sptmni anterior testrii

_____________________________________

- test diagnostic: ulcer hemoragic, atrofie gastric, limfom


MALT, dac pacientul este sub tratament cu antibiotice
sau IPP

_____________________________________

! Cu excepia serologiei, pentru celelalte teste, se ntrerup


IPP cu minim 2 sptmni naintea testrii.

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Testarea Helicobacter pylori

_____________________________________

Teste invazive:

_____________________________________
_____________________________________

Examenul histopatologic al materialului prelevat n timpul


EDS; specificitate > 95%

Testul rapid al ureazei: viraj colorimetric la schimbarea de pH;


specificitate 100%

_____________________________________
_____________________________________
_____________________________________

Cultura Hp din biopsia gastric

_____________________________________

- metod laborioas
- incubare n medii speciale 3-5 zile
- indicat n: - cazurile n care rezistena la antibiotic este peste 15
20% n aria geografic respectiv
- dup eecul a 2 cure de eradicare

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

22

Diagnosticul eficienei tratamentului


infeciei Hp

_____________________________________
_____________________________________
_____________________________________

Se face la distan - cel puin 4 sptmni de la terminarea


tratamentului

_____________________________________
_____________________________________
_____________________________________

Testul respirator - de elecie

_____________________________________

Ag n scaun

_____________________________________
_____________________________________

Testul serologic nu are valoare n testarea eficienei


tratamentului, scderea titrului Ac Hp necesit timp

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Indicaiile absolute de eradicare n infecia


cu Helicobacter pylori (Maastricht 4)

_____________________________________
_____________________________________
_____________________________________

Indicaii
UD/UG (activ sau complicat)
Limfom tip MALT
Gastrita atrofic
- pangastrit atrofie i metaplazie intestinal
adenocarcinom
- reversibilitatea leziunilor dup eradicare subiect
controversat
Gastrita de bont (stomac operat pentru cancer gastric)
Pacienii cu rude de gradul I cu istoric de cancer gastric
La cererea pacientului (consultarea prealabil a medicului
curant)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Alte indicaii pentru eradicarea infeciei


cu Helicobacter pylori

_____________________________________
_____________________________________
_____________________________________

Dispepsia functional
Boala de reflux gastroesofagian (BRGE)
Antiinflamatorii nesteroidiene (AINS)
Pediatrie
Alte afeciuni (trombocitopenie idiopatic, anemia prin deficit
de fier, deficitul de vitamin B12)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

23

_____________________________________

Dispepsia funcional

_____________________________________

principalele teste non-invazive ce pot fi utilizate pentru


strategia test and treat sunt testul respirator i Ag fecal;
sunt acceptate i testele serologice

_____________________________________
_____________________________________
_____________________________________
_____________________________________

test and treat este metod de elecie la adultul cu


dispepsie funcional i infecie cu Hp, n ariile cu
inciden crescut a infeciei Hp (> 20%)

_____________________________________
_____________________________________
_____________________________________

eradicarea Hp amelioreaza dispepsia pe o perioada lung


de timp

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

BRGE

_____________________________________

exist asociere negativ ntre prevalena infeciei Hp,


severitatea BRGE i incidena adenocarcinomului esofagian

_____________________________________
_____________________________________
_____________________________________

prezena Hp nu influeneaza severitatea simptomatologiei,


recurena sau eficiena tratamentului BRGE

_____________________________________

eradicarea Hp nu accentueaz BRGE preexistent i nu


influeneaz eficiena tratamentului cu IPP

_____________________________________

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Antiinflamatorii nesteroidiene (AINS)

_____________________________________

infecia cu Hp se asociaz cu risc crescut de apariie a


ulcerelor gastrice i duodenale la pacienii consumatori de
AINS sau doze mici de aspirin
eradicarea Hp reduce riscul de apariie a ulcerelor la
aceti pacieni
eradicarea Hp se recomand anterior iniierii AINS i
este obligatorie la pacienii cu istoric de ulcer peptic
simpla eradicare Hp - insuficient pentru prevenirea
ulcerului indus de AINS
incidena pe termen lung a HDS secundare ulcerului
peptic este mic dup eradicare, chiar n absena
proteciei gastrice

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

24

_____________________________________

Populaia pediatric
Ulcerul peptic
Copiii cu antecedente heredocolaterale de ulcer peptic
sau cancer gastric - testai i tratai
Anemia neexplicat i colica abdominal recurent testare Hp

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Alte afeciuni
Trombocitopenia idiopatic (TIP)
- > 50% din cei cu TIP au infecie Hp
- eradicarea infeciei Hp se nsoete de remisiunea
parial sau total a trombocitopeniei (explicat prin
reactivitatea ncruciat ale Ag de suprafa ale plachetei
i Hp)

_____________________________________

Anemia cronic prin deficit de fier fr cauz i


deficitul de vitamina B12 se amelioreaz la eradicarea
infeciei Hp

_____________________________________

_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________

_____________________________________

Infecia Hp i riscul de cancer gastric


Beneficiul major al strategiei de eradicare Hp - posibilitatea
de prevenire a cancerului gastric!

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Pacienii infectai cu Hp au inciden de 20 ori mai mare


de apariie a cancerului gastric comparativ cu populaia

_____________________________________
_____________________________________
_____________________________________

general.

_____________________________________
_____________________________________

OMS clasific Hp: carcinogen de grup I

_____________________________________
_____________________________________
_____________________________________

Terapia standard de eradicare pentru Hp


Maastricht IV 10-14 zile
IPP

CLARITROMICINA

METRONIDAZOL

AMOXICILINA

_____________________________________
_____________________________________
_____________________________________
_____________________________________

1.

IPP

500mg x 2/zi

2.

IPP

500mg x 2/zi

1000 mg x 2/zi

_____________________________________
_____________________________________

500 mg x 2/zi

_____________________________________
Qvadrupla terapie: SUBCITRAT DE BISMUT COLOIDAL 140mg x4/zi +
METRONIDAZOL 125 mg x4/zi+
TETRACICLINA 125 mg x4/zi+
IPP (20mgx2/zi) (pastil unic!)

_____________________________________
_____________________________________
_____________________________________

Omeprazol 20 mg x2/zi sau


Lansoprazol 30 mg x 2/zi sau
Pantoprazol 40 mg x 2 /zi sau
Rabeprazol 20 mg x2 /zi sau
Esomeprazol 20 mg x 2 /zi

_____________________________________
_____________________________________
_____________________________________

25

_____________________________________

IPP (indiferent de tipul folosit) au eficien > anti H2

_____________________________________

Doza trebuie respectat i fracionat - antibiotic, IPP

_____________________________________

Eficien: max 70%

_____________________________________
_____________________________________

Efecte secundare:
- dispepsie, diaree
- diareea este de obicei tranzitorie i autolimitat (cazuri rare cu
Clostridium difficile); se recomand folosirea probioticelor
- sunt mai frecvente n combinaia Claritromicin - Amoxicilin
(20%) comparativ cu Claritromicina i Metronidazol, motiv
pentru care se recomand Metronidazolul n zonele n care
rezistena la acesta este <15-20%
- unele probiotice i prebiotice mbuntesc rezultatele
tratamentului prin efectelor secundare

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Eecul terapiei de linia I

_____________________________________

Complian redus
Rezisten primar la antibiotice

_____________________________________
_____________________________________

- 15 - 66% pentru metronidazol, 2 - 30% pentru


claritromicin (n Europa de vest 2 - 3%; n Europa de
est i sud 20%)

_____________________________________
_____________________________________

- dac rezistena la Claritromicin este de 15-20% noul


consens recomand 14 zile n loc de 7 zile de tratament
i folosirea cvadruplei terapii (+ Subcitrat de Bismut
coloidal) n prima linie de tratament creterea ratei de
rspuns cu 12 %

_____________________________________

- rezistena primar la claritromicin este factor de risc


pentru eecul tratamentului

_____________________________________

- rezistena la amoxicilin apare extrem de rar

_____________________________________

_____________________________________
_____________________________________

_____________________________________

_____________________________________

Terapia de linia a II-a n eradicarea HP


(10-14 zile )

_____________________________________
_____________________________________
_____________________________________
_____________________________________

IPP n doze standard


Omeprazol 20 mg x 2/zi
Lansoprazol 30 mg x 2/zi
Pantoprazol 40 mg x 2/zi
Rabeprazol 20 mg x 2/zi
Esomeprazol 20 mg x 2/zi

Bismut
Subcitrat de
bismut 120
mg x 4/zi
sau
Amoxicilin
1g x 2 / zi

Tetraciclin

Metronidazol

_____________________________________
_____________________________________

500 mg x 3/zi

500 mg x 3/zi

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

26

_____________________________________

Terapia de linia a II-a n eradicarea HP

_____________________________________
_____________________________________

Rezistena secundar:
- metronidazol 60-70%
- claritromicin 30 %
Cea de-a doua linie de tratament determin eradicarea
infeciei Hp n 75% din cazuri
n zonele cu rezisten la claritromicin dup eecul
qvadruplei terapii se recomand tripla terapie cu
levofloxacina

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

LEVOFLOXACIN + AMOXICILIN + IPP


- este eficient n 90% din cazuri
- la 10 zile de tratament eradicarea este 94%
- levofloxacina este sigur i eficient

_____________________________________
_____________________________________
_____________________________________

_____________________________________

A III-a linie de tratament

_____________________________________
_____________________________________
_____________________________________

Dup eecul terapiei de linia a II-a tratamentul trebuie


ghidat prin testarea sensibilitii la antibiotic: endoscopie
cu prelevare de biopsie, cultur

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Terapia secvenial

_____________________________________
_____________________________________

Un modul secvenial de 10 zile a fost recent introdus


-5 zile IPP + Amoxicilin
-5 zile IPP + Tinidazol + Claritromicin 250 mg x 2/zi eradicare
radicare
Claritromicin 500 mg x 2/zi

_____________________________________
93%
94%

_____________________________________
_____________________________________
_____________________________________

Fr efecte secundare

_____________________________________
Terapia secvenial - eradicare semnificativ mai mare
comparativ cu terapia convenional 10 zile.

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

27

_____________________________________

Reinfecia

_____________________________________

Frecvena reinfeciei dup eradicare:


- n rile dezvoltate: 0,5 2%/an
- n rile n curs de dezvoltare 5%/an
Este mai curnd o recrudescen a bolii (pentru reinfecie
ar trebui demonstrat aceeai tulpin bacterian)

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Vaccinarea pentru Hp

_____________________________________

s-a dovedit eficient la animal, dar pentru a putea fi


recomandat la om necesit n continuare cercetri i studii
aprofundate

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Concluzii

_____________________________________
_____________________________________

tratamentul infeciei Hp este eficient

_____________________________________

rezistena la antibiotice trebuie cuantificat permanent


antibiotice alternative

_____________________________________

creterea duratei tratamentului 10-14 zile crete eficiena


cvadrupla terapie i terapia secvenial cresc succesul
tratamentului

_____________________________________
_____________________________________
_____________________________________
_____________________________________

cazurile care nu rspund la tratament necesit testarea


sensibilitii microbiene

_____________________________________
_____________________________________

monoterapia este o realitate ndeprtat n tratamentul infeciei


Hp

_____________________________________
_____________________________________
_____________________________________

28

BOALA DE REFLUX
GASTROESOFAGIAN
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Definiie:

totalitatea simptomelor i modificrilor histopatologice determinate de refluxul coninutului gastric n


esofag

_____________________________________
_____________________________________
_____________________________________

Ali termeni:

_____________________________________

boala de reflux endoscopic negativ

_____________________________________

BRGE noneroziv (simtome caracteristice prezente fr


modificri endoscopice ale mucoasei)
BRGE cu manifestri extradigestive

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Epidemiologie

_____________________________________

- extrem de frecvent
- n rile dezvoltate
-25% din populaie pirozis - o dat / sptmn
-7% pirozis - o dat / zi
- prevalena n cretere - dublarea n ultimele 2 decade
- distribuia - egal pe sexe

_____________________________________

Complicaii : M>F - esofagite (2-3 B/1F)

_____________________________________

_____________________________________

- esofag Barrett (10B/1F)

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

29

_____________________________________

Etiopatogenie

_____________________________________
_____________________________________

cea mai frecvent cauz - hernia hiatal prin alunecare


poate apare la orice cretere a presiunii abdominale: tuse,
corsete, ascit, tumori abdominale voluminoase, sarcin

_____________________________________
_____________________________________
_____________________________________
_____________________________________

vagotomie, gastrectomie, sclerodermie sau neuropatie


autonom diabetic

_____________________________________
_____________________________________

Atenie! Hp rol protectiv n BRGE (Hp gastrit antru i corp


masa celular parietal secreia acid, pH-ul gastric)

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Patogenie

_____________________________________

I.Incompentena mecanismelor de barier antireflux:


1. sfincterul esofagian inferior (SEI)
2. absena sau scurtarea segmentului intraabdominal
esofagian
3. unghiul Hiss lrgit - nu poate preveni refluxul

_____________________________________
_____________________________________
_____________________________________
_____________________________________

II.Clearence-ul esofagian prelungit

_____________________________________

III. ntrzierea evacurii gastrice (tulburri de motilitate gastroduodenale relaxarea tranzitorie SEI)

_____________________________________

IV. Coninutul refluxului - agresivitatea depinde de prezena i


concentraia de HCl

_____________________________________

V. Scderea capacitii de aprare a mucoasei esofagiene


(bicarbonat i prostaglandine).

_____________________________________

_____________________________________

_____________________________________

_____________________________________

_____________________________________

Tablou clinic

_____________________________________
_____________________________________

I. Manifestri digestive
Pirozis (arsur retrosternal, accentuat de alcool, alimente
iritante, fierbini, clinostatism)

Regurgitaia (refluarea coninutului gastric n esofag,


favorizat de clinostatism)
Sialoreea (consecina refluxului esofagian salivar declanat
de contactul coninutului gastric refluat cu mucoasa)
Disfagia (determinat de complicaii ale refluxului: stenoze
peptice, adenocarcinom)
Odinofagia (deglutiie dureroas) apare n esofagita sever

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

30

II . Manifestri extradigestive

_____________________________________

manifestri respiratorii (aspiraia materialului refluat n cile


aeriene, cu bronhospasm sau reflex vagal): traheobronite,
crize de dispnee expiratorie (bronhospasm), tuse cu caracter
cronic, nocturn (diagnostic diferenial cu dispneea paroxistic
nocturn din insuficiena ventricular stng)

_____________________________________
_____________________________________
_____________________________________
_____________________________________

manifestri cardiace (durat i volum refluat tulburri de


motilitate esofagiene): dureri precordiale noncardiace mimeaz angina pectoral i pot fi explicate parial prin
aciditate, durat i volumul coninutului refluat tulburri de
motilitate esofagian

manifestri ORL: arsuri bucale, gingivit, eroziuni dentare,


senzaie de corp strin, laringit (cea mai frecvent),
laringospasm, otit medie, sinuzit

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Explorri paraclinice

_____________________________________
_____________________________________

I. Endoscopia
- indicat la toi pacienii cu simptome de alarm pentru
BRGE ct i la cei care nu rspund la tratament
- specificitate foarte bun (90-95%), diagnostic etiologic i
al complicaiilor BRGE
- exclude afeciuni asociate (ulcere gastrice, duodenale)
- permite tratamentul n unele complicaii ale BRGE
(stenoze, esofag Barrett)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Simptomele de alarm n BRGE: disfagia, odinofagia,


scderea n greutate, anemia, HDS, istoric de cancer de
tract digestiv superior

_____________________________________
_____________________________________
_____________________________________

_____________________________________

Esofagita peptic - 30% din pacieni

_____________________________________

Clasificarea Savary Miller (1977):


grad 0 esofag macroscopic normal
grad I: eroziuni neconfluente eritematoase sau
eritematoexudative pe un singur pliu;
grad II: eroziuni multiple, confluente, necircumfereniale,
pe mai multe pliuri;
grad III: eroziuni confluente, circumfereniale;
grad IV: ulcer, strictur, izolat sau asociat cu II, III;
grad V: esofag Barrett I-III.

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

31

_____________________________________

Clasificarea Los Angeles (1994)

_____________________________________

Grad A: una sau mai multe pierderi de substan, dar nici


una nu depete 5mm n lungime;

_____________________________________
_____________________________________

Grad B: cel puin o eroziune peste 5 mm dar fr leziuni


confluente ntre 2 pliuri;

_____________________________________

Grad C: cel puin o eroziune confluent ntre unul sau


mai multe pliuri dar nedepind 75% din circumferin;

_____________________________________

Grad D: pierdere de substan (ulcere) > 75% din


circumferina esofagului.

_____________________________________

_____________________________________

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________

II. Examenul radiologic baritat

_____________________________________

valoare diagnostic redus


evideniaz hernia hiatal, tulburri de motilitate, complicaii
(stenoze, tumori)

_____________________________________
_____________________________________
_____________________________________
_____________________________________

III. Monitorizarea pH-ului esofagian

_____________________________________

metoda cea mai sensibil, permite nregistrarea episoadelor


de reflux, durata, momentul apariiei
Asociaia American de Gastroenterologie recomand n
cazuri selecionate :
preoperator i postoperator dac simptomatologia persist;
lipsa de rspuns la tratamentul cu IPP cu persistena
simptomelor i endoscopie normal;

durere toracic non-cardiac sau BRGE cu manifestri


ORL sau de astm non-alergic.

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

IV. Manometria esofagian

_____________________________________

nu are valoare diagnostic n BRGE


nu exist corelaii ntre presiunea bazal a SEI i
simptomatologie sau gradul esofagitei
diagnosticul diferenial cu tulburri motorii esofagiene
(achalazia)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

V. Scintigrafia

_____________________________________

are sensibilitate sczut


se folosete n special la copii pentru aprecierea refluxului i a
clearence-ului esofagian

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

32

_____________________________________
_____________________________________
_____________________________________

VI. BILITECH

_____________________________________

aprecierea refluxului alcalin


procedeu asemntor pH-metriei
colecistectomizati, stomac operat

_____________________________________
_____________________________________
_____________________________________

VII. Impedana esofagian

_____________________________________

diferenierea refluxului funcie de consisten (solid,


lichid etc)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Diagnosticul complicaiilor

_____________________________________

I. Stenozele esofagiene benigne

_____________________________________
_____________________________________

complic BRGE n 12% din cazuri


factori favorizani:
refluxul prelungit
intubaie nazo-gastric
gastrectomie
sclerodermie - 1/3 inferioar esofag
disfagie - lumenul este mai ngust de 12 mm
prevenire stenoze peptice - instituire precoce a tratamentului
medical

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

II. Esofagul Barrett (EB)

_____________________________________
_____________________________________

Definiie: nlocuirea epiteliului scuamos din 1/3 inferioar a


esofagului cu epiteliu metaplazic de tip columnar

Diagnostic: prelevare de biopsie din 4 cadrane la 2 cm distan


identific gradul de displazie atitudinea terapeutic

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Complicaii: ulceraii, stenoze, adenocarcinom

_____________________________________
_____________________________________

Factori de risc pentru adenocarcinom: hernia hiatal


voluminoas, esofag Barett cu segment lung i displazia

_____________________________________
_____________________________________
_____________________________________

33

III. Hemoragia digestiv superioar (2-6%)


este relativ rar, legat de BRGE complicat (ulcere, EB)
pierderi de snge cronice, evideniate prin anemie
hipocrom, feripriv n BRGE complicat

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

IV. Adenocarcinom esofagian

_____________________________________

complicaie a EB

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Diagnostic diferenial

_____________________________________

I. Afeciuni esofagiene

_____________________________________

Esofagite de alt etiologie (postcaustic, postradic etc.) anamnez i EDS


Neoplasmul esofagian - EDS cu examen histopatologic din
biopsia prelevat
Achalazia cardiei - lipsa de relaxare a SEI cu nlocuirea
contraciilor primare cu contracii teriare aperistaltice examen endoscopic, manometrie radiologie
Spasmul difuz esofagian - examen radiologic, EDS,
manometrie

_____________________________________

Tulburri de motilitate secundare afeciunilor sistemice (diabet


zaharat, sclerodermie etc)

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________

_____________________________________

II. Afeciuni extraesofagiene

_____________________________________
_____________________________________

Angina pectoral - pH-metrie/ 24h i test Bernstein


- pot fi afeciuni intricate

_____________________________________
_____________________________________

Astmul bronic - anamnez i pH-metrie


- pot fi afeciuni intricate

_____________________________________
_____________________________________

Colonul iritabil, dispepsia non-ulceroas, ulcerul gastric i


duodenal - simptome similare celor din BRGE

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

34

_____________________________________

Tratament

_____________________________________

BRGE necomplicat

_____________________________________

Obiective:

_____________________________________
_____________________________________

prevenirea, reducerea, dispariia simptomelor de reflux


vindecarea - ameliorarea leziunilor histologice
prevenirea complicaiilor i recurenelor
diminuarea necesitii interveniilor chirurgicale

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Regimul igieno-dietetic

_____________________________________
_____________________________________

Schimbarea obiceiurilor i comportamentului zilnic:


Alimentaie fracionat, prnzuri reduse cantitativ, repetate
(5-6/zi)

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Evitare alimente iritante pentru mucoasa esofagian prin


contact direct i prin reducerea presiunii SEI: alcool,
ciocolat, cafea, ceai negru, grsimi animale, tomate, citrice,
aluaturi dospite cu drojdie, arahide, dulciuri concentrate

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Evitarea alimentelor fierbini sau foarte reci

_____________________________________

Interzicerea fumatului

_____________________________________
_____________________________________

Evitarea decubitului postprandial (ultima mas cu minim o or


nainte de culcare)

_____________________________________
_____________________________________
_____________________________________

Recomandri posturale: n timpul somnului capul ridicat la 15


Reducerea presiunii intraabdominale: renunare la corset i
curele strnse, mbrcminte lejer, regim hipocaloric n cazul
pacienilor supraponderali, combaterea constipaiei,
meteorismului, evitarea poziiei de anteflexie, combaterea
tusei

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Evitarea consumului de medicamente iritante (AINS) sau care


scad presiunea SEI: calcium-blocante, estro - progestative,
aminofilin, anticolinergice, neuroleptice etc

_____________________________________
_____________________________________
_____________________________________
_____________________________________

35

_____________________________________

Tratamentul medicamentos

_____________________________________

1. Medicatia antiacid

_____________________________________

Alcalinele (pe baz de aluminiu i magneziu)


Mecanisme de aciune: - neutralizeaz aciditatea gastric
- cresc pH-ul esofagian
- inactiveaz pepsina
Mod de administrare: 5 - 6 prize/zi la 1 h postprandial (durata
maxim de aciune 60)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Avantaje: - ieftine
- aciune favorabil imediat
- perioade scurte de timp, remisie de moment a
simptomatologiei

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

2 . Medicaia antisecretorie

_____________________________________

Blocanii receptorilor histaminergici H2


(Cimetidina, ranitidina, famotidina, roxatidina)

_____________________________________
_____________________________________

Recomandate n boala de reflux form uoar sau medie


Mecanism de aciune: blocheaz competitiv receptorii H2 din
celulele parietale gastrice scad secreia gastric acid
Mod de administrare: nainte de mese
Eficiena invers proporional cu severitatea esofagitei
Efecte secundare numeroase, controversate - Nu se
administreaz pe termen lung

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Inhibitorii pompei de protoni (omeprazolul, pantoprazolul,


esomeprazolul, lansoprazolul, rabeprazolul)

_____________________________________
_____________________________________

Mecanism de aciune: blocheaz pompa de hidrogen ATP-aza


din vrful celulei parietale gastrice
Eficien > inhibitorii H2, maxim dac se administreaz cu
30 minute naintea meselor (celula parietal - numr mare de
pompe de protoni active)
doze famacologice echivalente - efect identic (studii de
specialitate)
Mod de administrare: o priz/ zi - forme uoare
dou prize / zi - forme medii sau severe:
OMEPRAZOL 20mg/zi 20x2/zi
LANSOPRAZOL 15mg/zi 15x2/zi
PANTOPRAZOL 20mg/zi 20x2/zi
RABEPRAZOL 20 mg/zi 20x2/zi
ESOMEPRAZOL 20mg/zi 20x2/zi

36

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Efectele secundare
Minore: cefalee, diaree
Severe: - precipit osteoporoza fracturi osoase
- nefrite interstiiale
- hepatite
- atrofie gastric, polipi
- precipit evoluia colitei cu Clostridium difficile
Noi ageni terapeutici
Dexlansoprazolul (SUA) (tb 30mg) cu eliberare lent.
- tratamentul simptomelor de reflux vindecare esofagit
indiferent de severitate dup 8 sptmni de tratament

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Medicaia prokinetic

_____________________________________
Determin acentuarea golirii gastrice, creterea presiunii
SEI,creterea clearance-ului esofagian
Metoclorpramida (10 mgx 3/zi)
- amelioreaz acuzele
- cu 30 min nainte de mese
subiective
- utilizare limitat efecte de tip
- nu amelioreaz
Extrapiramidal i psihotrop (vrstnic)
aspectul
Domperidonul (10mgx3/zi)
endoscopic i
- efecte secundare mai puine
histopatologic

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Cisaprida - retras de pe pia - efecte cardiace grave


(tahicardie ventricular, prelungire QT, moarte subit)

_____________________________________
_____________________________________
_____________________________________

Medicaia topic de protecie a mucoasei

_____________________________________
_____________________________________

Sucralfatul 1000 mg x 4 / zi
cu 30 minute nainte de mese i la culcare (pelicul
protectoare)
esofagita de grad III sau IV

Alginat (Gaviscon) 10 - 20ml suspensie, 4 ori/zi


se administreaz postprandial i nainte de culcare
BRGE complicaii n asociere cu antisecretorii

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Mecanisme de aciune (alginate): barier mecanic anti-RGE;


activ pe refluxul acid i alcalin

_____________________________________
_____________________________________
_____________________________________

37

_____________________________________

Strategii de tratament medicamentos

_____________________________________

step - up- regim igieno dietetic antiacide prokinetice


blocani histaminici H2 IPP

_____________________________________
_____________________________________

top - down - IPP (doz standard 6 - 8 sptmni)


njumtirea dozelor IPP blocani histaminici H2
prokinetice antiacide regim igieno dietetic

_____________________________________

Lipsa de rspuns la tratament medical:


Pacient necooperant, stil de via neadecvat
Existena unei complicaii boal asociat
Tratament medical insuficient

_____________________________________

_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tratament chirurgical

_____________________________________

clasic sau laparoscopic - fundoplicatura Nissen

_____________________________________

Indicaii:

_____________________________________

Simptomatologie persistent cu tratament medical corect


administrat
Compliana redus a pacientului la tratament de lung durat
Recderi frecvente
Stenoze esofagiene strnse cu eec la dilatarea endoscopic
Complicaii pulmonare severe (bronhopneumopatie de
aspiraie suprainfectat, astm bronsic cu crize subintrante)
Esofag Barret cu displazie sever (adenocarcinom)

_____________________________________

NB. complicaii - 20-50% din cazuri


- deces postoperator 0,4-1,5% (laparoscopic < chirurgie
clasic)

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________

_____________________________________

Tratamentul endoscopic

_____________________________________
_____________________________________

nu este extrem de bine structurat ca indicaie n BRGE


proceduri: - radiofrecvena
- sutura endoscopic a jonciunii eso-gastrice

_____________________________________
_____________________________________
_____________________________________

- s-a renunat n prezent la injectarea de substane nonabsorbabile la nivelul jonciunii pentru ngustarea lumenului
(lipsa de standardizare)
Complicaii - n general uoare
- rar, complicaii severe: pneumonii de aspiraie,
mediastinit i hemoragie digestiv superioar

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

38

_____________________________________

Tratamentul complicaiilor

_____________________________________
_____________________________________

Stenoze esofagiene:

_____________________________________
_____________________________________

Dilatare endoscopic (dilatatoare Savary cu diametre


progresive i sedine succesive)
Atenie: dilatarea favorizeaz refluxul + IPP postdilatare
Laparoscopic sau chirurgical clasic - rezecie stenoz
corecie hernie + dispozitiv antireflux

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Esofagul Barrett

_____________________________________

Toi pacienii cu esofag Barrett - tratament cu IPP


Supraveghere endoscopic : risc de cancer- 0,5% / an,
1/200 pacieni
EB fr displazie sau displazie de grad jos supraveghere
la 2-3 ani (fr diferene n apariia adenocarcinomului)
EB cu displazie de grad nalt - rezecie endoscopic
mucosal + alte tehnici ablative (terapie fotodinamic);
tehnicile ablative complicaii chirurgia EB

_____________________________________

Chemoprevenia pentru a mpiedica progresia displaziei aspirin i inhibitori COX2 (fr standardizare)

_____________________________________

Factori de risc pentru adenocarcinom: hernie hiatal mare,


EB cu segment lung i displazia mucoasei

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

_____________________________________
_____________________________________

_____________________________________

Esofagita alcalin

_____________________________________
_____________________________________

rar; gastrectomizai /atrofia gastric din anemia Biermer

_____________________________________
_____________________________________

Regim igieno-dietetic similar esofagita peptic


Colestiramina 1g x 4/zi (chelatoare de sruri biliare)
Nu se administreaz inhibitori ai secreiei gastrice

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

39

40

TULBURRI MOTORII
ESOFAGIENE
_____________________________________

Definiie: lipsa coordonrii peristalticii esofagiene cu

_____________________________________

deglutiia determin apariia tulburrilor motorii esofagiene.

_____________________________________
_____________________________________

Etiologie

_____________________________________

I. Primare
II. Secundare
Afeciuni metabolice (diabet zaharat)
Intoxicaii (alcoolism)
Afeciuni endocrine(hipo i hipertiroidie)
Afeciuni neurologice (accidente vasculare cerebrale,
pseudobulbarism, Parkinson)
Afeciuni musculare (miastenia gravis)
Colagenoze (lupus eritematos sistemic, sclerodermie)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Clasificarea Chicago a tulburrilor motorii


esofagiene (HRM high resolution manometry)
Cu relaxare normal a
jonciunii eso-gastrice

Cu afectarea relaxrii
jonciunii eso-gastrice

- Absena peristalticii
- Peristaltic hipotensiv
(intermitent, frecvent)
- Peristaltic hipertensiv
- Esofagul sprgtor de nuci
- Spasmul esofagian
(segmentar sau difuz)

- Acalazia cardiei (clasic, cu


compresiune esofagian,
spastic)
- Obstrucia funcional a
jonciunii eso-gastrice

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

41

_____________________________________

ACALAZIA CARDIEI

_____________________________________

Definiie:

tulburare motorie esofagian caracterizat


prin absena relaxrii sau relaxare incomplet a SEI cu
deglutiia i nlocuirea undelor peristaltice primare cu
contracii teriare aperistaltice

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Epidemiologie

_____________________________________

- 1-5/ 100.000 locuitori

_____________________________________

- 20-60 de ani
-F B

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Etiopatogenie

_____________________________________

Teorii :
- viral (varicela zoster, rujeol)
- toxic
- genetic (mai frecvent la pacienii cu sindrom Down,
sindrom AAA: acalazie, alacrimie, Adisson)
- autoimun (cea mai acceptat teorie infiltrarea
plexului mienteric cu limfocite CD3 CD8 pozitive, Ac
IgM, activarea complementului)
Modificri la nivelul sistemului nervos:
- afectarea selectiv a neuronilor inhibitori de la nivelul
plexului mienteric, cu producerea de VIP, NO i infiltrat
inflamator - disfuncia SEI
- modificri degenerative la nivelul nucleului dorsal al
vagului i a ramurilor vagale

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Tablou clinic

_____________________________________

1.

Disfagia
- localizare la nivelul esofagului inferior, retroxifoidian
- debut insidios, sau brusc dup stress
- poziii care cresc presiunea intratoracic (Valsalva,
ridicarea braelor, ndreptarea spatelui)
- 50% disfagie paradoxal
2. Durerea toracic anterioar
- de obicei la nceput, nainte de dilatarea esofagului
- iradiaz la nivel cervical i omoplai
- acalazia viguroas
3. Regurgitaia
- alimente nedigerate, amestecate cu saliv (NU cu acid
sau bil)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

42

_____________________________________
_____________________________________
_____________________________________

4. Pirozisul
- produs de acidul lactic ce rezult din fermentaia
alimentelor i nu de RGE

_____________________________________
_____________________________________
_____________________________________

5. Simptome pulmonare (staz pulmonar, regurgitare,


aspiraie n arborele traheo-bronic):
- tuse nocturn
- wheezing

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Examen obiectiv - normal


Probe biologice - nemodificate

_____________________________________
_____________________________________
_____________________________________

Diagnostic paraclinic

_____________________________________
_____________________________________

EDS
Manometria
Examenul radiologic

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

EDS

_____________________________________

Esofag dilatat cu resturi alimentare i staz


Cardia nchis (semnul rozetei)
Endoscopul trece cu uurin n stomac prin cardia
nchis

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Ecoendoscopie - difereniaz acalazia


pseudoacalazie (infiltrarea tumoral a cardiei)

de

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

43

_____________________________________

Manometrie

_____________________________________
_____________________________________

Absena relaxrii SEI ca rspuns la deglutiie

_____________________________________

Absena undelor peristaltice primare

_____________________________________

Presiunea SEI este de obicei crescut (N 15-20 mm Hg)


Teste
farmacologice
(mecholyl,
bethanecol,
colecistokinin): cresc presiunea SEI fr peristaltic
esofagian asociat

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Manometria de nalt rezoluie (high resolution


manometry - HRM)

_____________________________________
_____________________________________
_____________________________________

HRM asociat cu graficul topografic al presiunilor a permis


identificarea a 3 tipuri de acalazie:
- Tipul I (acalazia clasic): afectarea relaxrii SEI fr
creterea presiunii la nivel esofagian
- Tipul II (acalazia cu compresiune): nghiirea apei duce
la creterea presiunii la nivelul esofagului, care poate
depi presiunea SEI, determinnd golirea esofagului
- Tipul III (acalazia spastic): creterea presiunii la nivelul
esofagului prin contracii obliterante datorate ngustrii
lumenului

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Manometria de nalt rezoluie (high resolution


manometry - HRM)

_____________________________________
_____________________________________
_____________________________________

St la baza noii clasificri a tulburrilor motorii


esofagiene (Clasificarea Chicago)

_____________________________________
_____________________________________
_____________________________________

Tehnic util n stabilirea:


- prognosticului
- terapiei (cele mai bune rezultate terapeutice se obin n
tipul II)
- accesibilitate redus!

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

44

_____________________________________

Examenul radiologic

_____________________________________

Rx.torace
- nivel hidro-aeric mediastinal
- dispariia camerei cu aer a stomacului
- complicaii pulmonare

_____________________________________
_____________________________________
_____________________________________

Rx. baritat eso-gastric


- dilatarea corpului esofagian (aspect tortuos, sigmoidian)
- staz esofagian
- ngustare simetric, axial, conic, regulat n regiunea
terminal (cioc de pasre, min de pix)
- bolusul baritat nu trece cardia sau este eliminat fracionat

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Diagnostic diferenial

_____________________________________
_____________________________________

Cancerul cardiei (pseudoacalazia): vrst naintat,


istoric scurt al disfagiei , EDS cu biopsie, ecoendoscopie

_____________________________________

Alte tulburri motorii esofagiene (SDE, esofagul


sprgtor de nuci): examen radiologic, manometrie

_____________________________________

Boala Chagas (Tripanosoma cruzi): America de Sud; se


nsoete de megacolon, megaureter (distrugerea
plexurilor mienterice)

_____________________________________

_____________________________________

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Complicaii

_____________________________________

Esofagiene
- esofagit
- HDS
- cancer esofagian (risc de 7x ! comparativ cu populaia
general, att pentru carcinom scuamos, ct i
adenocarcinom, n special la sexul masculin); nu exist
ghiduri pentru screening!

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Pulmonare
- bronite, broniectazii
- infiltrate pulmonare
- abces pulmonar

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

45

_____________________________________

Tratament

_____________________________________
_____________________________________
_____________________________________

MEDICAL

_____________________________________
_____________________________________

ENDOSCOPIC

CHIRURGICAL

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tratament medical

_____________________________________

Ageni farmacologici miorelaxani (se administreaz cu


45 minute nainte de mas)
- nitrai (ISDN) 5-10 mg
- blocani de canal calcic (Nifedipin 10-40 mg)
- sildenafil (Viagra): blocheaz fosfodiesteraza, GMPc
relaxare muscular
eficacitate redus, se utilizeaz numai n formele
incipiente de boal

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Tratament endoscopic

_____________________________________

1. Dilatarea endoscopic cu balon


- contraindicaii: infarct miocardic recent, pacient
necooperant,
esofag
pseudosigmoidian,
diverticul
epifrenic, hernie hiatal
- complicaii: perforaie, HDS, BRGE
- rezultate: ameliorarea disfagiei n 65-90% din cazuri

_____________________________________

2. Injectarea intrasfincterian de toxin botulinic


- blocarea eliberrii acetilcolinei la nivel presinaptic
- 80 UI n 4 cadrane
- se repet la 6-18 luni
- rezervat cazurilor cu patologie asociat sever

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

46

Tratament endoscopic

_____________________________________
_____________________________________

3. Tehnici noi: necesit confirmare i evaluarea rezultatelor


pe termen lung
- stentare (stent autoexpandabil)
miotomia
endoscopic
peroral
(POEM):
secionarea fibrelor musculare circulare esofagiene printrun tunel submucos creat prin abord endoscopic la nivelul
mucoasei esofagiene

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tratament chirurgical

_____________________________________
_____________________________________

Miotomie longitudinal extramucoas (Heller)


- laparoscopic
- se asociaz cu o tehnic antireflux

_____________________________________
_____________________________________
_____________________________________

Indicaii: pacieni tineri (40 45 ani), complicaii pulmonare,


n caz de eec al tratamentului endoscopic

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

SPASMUL DIFUZ ESOFAGIAN


Tulburare motorie esofagian , mai frecvent la persoanele n
vrst , caracterizat printr-o proporie crescut de contracii
aperistaltice cu relaxare normal a SEI

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Clinic: disfagie, durere retrosternal

_____________________________________

Examen radiologic baritat: aspect de tirbuon

_____________________________________
_____________________________________

EDS:
inele etajate
exclude alte cauze de disfagie

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

47

SPASMUL DIFUZ ESOFAGIAN


Manometria esofagian
- contracii aperistaltice ca rspuns la mai mult de 30% din
deglutiii
- creterea amplitudinii i duratei undelor peristaltice
- presiunea SEI i relaxare la deglutiie normale

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Diagnostic diferenial:
- achalazia cardiei( manometrie, EDS, examen radiologic)
- cancer esofagian
- stenoza esofagian peptic

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Tratament
- relaxante musculare (nitrai, nifedipin)
- IPP (legtur RGE SDE?)
- anxiolitice, antidepresive

_____________________________________
_____________________________________
_____________________________________

48

CANCERUL ESOFAGIAN
_____________________________________
_____________________________________

Epidemiologie

_____________________________________
_____________________________________

Este a noua cauz de cancer pe glob


Mai frecvent la sexul masculin (B/F2)
Dup 50 de ani, inciden maxim 60-70ani
Incidena anual pe glob-variabil (sex, ras, regiune
geografic, situaie socioeconomic) (5x105 n SUA, 18-26

_____________________________________

x105 n Frana, 100x105 n Linxian China)

_____________________________________

_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Cancer esofagian
1. Adenocarcinom
2. Scuamos

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Factori de risc

Adenocarcinom

_____________________________________

- BRGE, esofagul Barrett ( displazia sever, esofag

_____________________________________

Barett segment lung), hernia hiatal voluminoas

_____________________________________
_____________________________________

- obezitatea

_____________________________________
_____________________________________
_____________________________________

49

Factori de risc

_____________________________________

Carcinom scuamos
- fumat, alcool
- marii fumtori-risc de 5x> comparativ cu nefumtorii
- alcoolici risc de 20-50X >
- tutunul+ alcoolul (efect sinergic) x100 >
- statusul socio-economic precar
- diet srac n legume, fructe, vitamine (B,C), Mg, Zn,
proteine
- afeciuni esofagiene: acalazia cardiei, stenozele esofagiene,
sindrom Plummer Vinson
- cancer ci aero-digestive superioare
- tyloza (keratodermie plantar i palmar, papiloame
esofagiene i cancer esofagian) se transmite autosomal
dominant
- factori posibili implicai: concentraia de molibden din sol,
petrol, solveni, virusul papilomatos uman, boala celiac
- radiaiile toracice pentru cancer de sn cresc de 10x riscul de
cancer esofagian

Tablou clinic

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

cancerul esofaian precoce-asimptomatic


disfagia progresiv (apare cnd tumora ocup peste din
lumenul esofagian)
durere toracic
regurgitaii, halen fetid, eructaii, hipersialoree
scdere n greutate, caexie
HDS
simptome secundare invaziei locale: fistule eso-bronice,
pleurezie, mediastinit, voce bitonal (paralizie recurent)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

de la instalarea semnelor de alarm pn la momentul


diagnosticului 1-2 luni

_____________________________________
_____________________________________

Examen obiectiv: semne de invazie, compresiune,


denutriie

_____________________________________
_____________________________________

Explorri paraclinice

_____________________________________

EDS
CE precoce (limitat la mucoas i submucoas fr
metastaze ganglionare): zon supradenivelat minim,
ulceraie superficial, polip
- cromoscopia, magnificaia, narrow band imaging
(NBI) cresc calitatea diagnosticului endoscopic

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

CE avansat: vegetant, exofitic, conopidiform, ulcerovegetant, infiltrant: stenoz asimetric


Confirmare diagnostic - histopatologie din biopsia
prelevat din leziune

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

50

_____________________________________

Examenul radiologic baritat

_____________________________________

imagine lacunar neregulat unic sau multipl


ni ncastrat n lacun
stenoz excentric, neregulat

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Explorrile biologice
nu aduc date suplimentare pentru diagnostic
anemie
teste hepatice alterate n cazul metastazelor

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Explorri pentru stadializare


Rx toracic-fistule i metastaze pulmonare

_____________________________________
_____________________________________
_____________________________________

Ecografie abdominal evaluarea metastezelor hepatice


Ecoendoscopie-stabilirea profunzimii leziunii tumorale,
metastaze ganglionare

_____________________________________
_____________________________________
_____________________________________
_____________________________________

CT torace i abdomen - are rezultate identice cu RMN-ul stadializeaz cancerul, metastazele locoregionale i la distan
Tomografia cu emisie de pozitroni (PET) indicat n cazuri
selecionate pentru decelarea disminrilor la distan

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Evoluie, prognostic

_____________________________________
_____________________________________

Evoluie rapid, invazie local, metastaze locale sau


regionale

_____________________________________
_____________________________________

Supravieuire la 1 an sub 75% n absena tratamentului

_____________________________________
_____________________________________

Tratament

_____________________________________

Chirurgical
Endoscopic
Radioterapie
Chimioterapie

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

51

_____________________________________

Tratament chirurgical

_____________________________________

Curativ: esofagectomie extins cu limfadenectomie i


restabilirea continuitii (esofagoplastie) cu stomac sau
colon
Paliativ: gastrostom, stent, rezecie paliativ
Contraindicaii
Metastaze ganglionare sau la distan
Invazia aortei, pericardului, pleurei, diafragmului
Fistul esotraheal, esobronic
Insuficien respiratorie
Ciroz hepatic
Infarct miocardic recent
Denutriie sever (peste 20% din greutatea corporal)
Vrst peste 75 ani

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Tratament endoscopic

_____________________________________

Curativ: mucosectomia endoscopic - ntr-un centru cu minim


10 ani de experien
Criterii pentru tratament endoscopic cu viz curativ:
tumora s nu depeac inelul mucos,neulcerat, fr invazie
limfatic sau vascular
Paliativ
Proteze esofagiene-stent
Indicaii: cancer avansat, inoperabil; fistule eso-bronice
Contraindicaii: leziune nalt (sub 2 cm de SES), obstrucie
luminal complet, bolnav terminal
Complicaii (40%): durere, migrarea, stenoza sau obstrucia
stentului)
Tratamentul tumorii endoscopic cu laser i argon-plasmacu recidiv tumoral la 4-6 sptmni
Gastrostoma endoscopic percutan

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Radioterapia, chimioterapia

_____________________________________
_____________________________________

Rezultate puin eficiente, n special pentru adenocarcinom

_____________________________________
_____________________________________

Brachiterapia amelioreaz disfagia n 70% din cazuri,


fr prelungirea duratei de via
Chimioterapia n cancerul esofagian avansat
(cisplatin/vinorelbin, capecitabine/docetaxel) are eficien
parial n mai puin de 1/3 din cazuri

_____________________________________
_____________________________________
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52

ULCERUL GASTRIC
I DUODENAL
_____________________________________

Definiie

afeciune plurifactorial, cu evoluie cronic


ondulant. Se caracterizeaz histopatologic printr-o pierdere de
substan care depaete n profunzime musculara mucoasei,
nconjurat de un infiltrat inflamator, la nivelul mucoasei gastrice
i/sau duodenale

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_____________________________________
_____________________________________
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Epidemiologie

_____________________________________

- prevalena global - 10%


- tendin de scdere a frecvenei n ultimele decade, probabil
legat de eradicarea Hp; creterea ulcerelor AINS
- incidena maxim - decada a 4-a - UD
- decada a 5-a i a 6-a - UG
- UD - de 2-3 ori mai frecvent dect UG
- UD - de 2-3 ori mai frecvent la brbai
- UG brbai/femei = 1,5/1
- mortalitatea 1%

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Etiopatogenie (1 9)

_____________________________________

1.

Agresiunea clorhidro peptic no acid- no ulcer

_____________________________________

2.

Infecia Helicobacter pylori:


- ulcerogeneza: no Hp no ulcer
- recdere
UD - infecia Hp 80-90 %
UG infecia Hp 60-70 %
Antiinflamatoarele
- actiune iritativ local
- reducerea sintezei de prostaglandine
- influenteaza negativ secretia de mucus i bicarbonat
- >50% consumatorii de AINS - ulceraii superficiale
- apar mai frecvent la vrstnici
- favorizeaz complicaiile

_____________________________________

3.

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4. Alimentatia
- anumite alimente pot favoriza dispepsia dar nu exist
relaie direct diet ulcer, inclusiv pentru alcool i cafea

53

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_____________________________________

5. Stress - ul
- relatie ntre peptidele cerebrale i tubul digestiv prin
influenarea secreiei i motilitii gastrice
- stress - ul acut - ulcere de stress
- gastrita hemoragic acut
- stress - ul cronic factor ulcerogen
6. Boli asociate
- asociere cert: mastocitoza sistemic, boli pulmonare
cronice, IRC, CH, litiaza renal, deficitul de alfa-1 antitripsin
- asociere probabil: hiperparatiroidismul, bolile coronariene,
policitemia vera, pancreatita cronic

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7. Factorul genetic
- Rudele de grd I ale pacienilor cu UD risc de 3 x >
- grupul sanguin O(I) , nesecretor - risc 1,5 x >

_____________________________________
Rol HP?

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_____________________________________
_____________________________________

8.

Fumatul crete incidena, frecvena recderilor i apariia


complicaiilor n ulcerul peptic
stimuleaz secreia acid
interfer cu antagonitii H2
crete evacuarea gastric a lichidelor
crete refluxul duodenogastric
diminu secreia pancreatic de bicarbonat
diminu fluxul sanguin mucos
inhib producerea prostaglandinelor la nivelul mucoasei

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9. Cauze rare
- infecii: citomegalovirus, herpes simplex
- medicamente: bisfosfonaii, chimioterapia, clopidogrel,
glucocorticoizii, clorura de potasiu
- alte afeciuni: boli mieloproliferative, obstrucie duodenal
(ex. pancreas inelar), ischemie, radioterapie, sarcoidoz,
boal Crohn

_____________________________________

Fiziopatologie

_____________________________________

Factori de agresiune
Factori de aprare
Acidul clorhidric
Preepitelial
- masa celulelor parietale
- mucus
- tonusul vagal
- bicarbonat
- hipersecreia i sensibilitatea la gastrin
- eliberare crescut de histamin
Epitelial
Pepsina
- refacerea esuturilor
- pepsinogenul I
- celule epiteliale
Refluxul duodeno gastric
- prostaglandine
- factor epidermal de
cretere
- sruri biliare
- secreia pancreatic
Subepitelial
- secreia intestinal
- flux sanguin
(microcirculatie)
- aport nutritiv
- oxigenare

54

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Morfopatologie

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Macroscopic
- majoritatea unice; 5% - 10% - ulcere duble/multiple
- localizarea UD - peretele anterior sau posterior duodenal
- UG - mica curbur vertical (cel mai frecvent)
- forma - rotund / ovalar; pot fi - triunghiulare, n halter,
n rachet de tenis
- dimensiuni minime gigante (3-4 cm)
- pliuri convergente spre craterul ulceros

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Microscopic

_____________________________________

- pierdere de substan care depete musculara mucoasei,


asociat cu infiltrat inflamator acut (neutrofile faz de
activitate) sau cronic (infiltrat limfo-plasmocitar cicatrizare)
gastrit antral duodenit

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tablou clinic
- Durerea epigastric
- ritmicitatea - UD - tardiv post alimentar (90 min 3 h)
- trezete pacientul noaptea (0 3 am)
- UG la 30 min 1h postprandial
- periodicitate primvara , toamna
- calmat de alimente n UD, poate fi accentuat n UG
- Greuri , vrsturi acide
- Scderea n greutate i anorexia UG
- Nu exist corelaie clinico lezional
- Pot debuta printr-o complicaie
Examen obiectiv
- facies ulceros supt, cu pomei proemineni
- complicaii paloare, tahicardie, abdomen de lemn, clapotaj
- palpare sensibilitate epigastric sau paraombilical drept

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Diagnostic

_____________________________________
_____________________________________
_____________________________________

Anamnez: simptomatologie, antecedente heredocolaterale, fumat, AINS, afeciuni asociate

_____________________________________
_____________________________________

Evidenierea infeciei Hp: metode invazive/non-invazive

_____________________________________
_____________________________________

EDS

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_____________________________________

Examen radiologic baritat

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55

_____________________________________

Endoscopia digestiv superioar

_____________________________________
_____________________________________

- evideniaz leziunea ulceroas


- acoperit cu o membran alb - sidefie de fibrin
- aspectul mucoasei din jur

_____________________________________
_____________________________________

- permite identificarea infeciei Hp (test rapid ureazic,


examen histologic, culturi)
- n toate UG biopsii multiple din marginea ulcerului
- UD de regul nu se analizeaz histopatologic

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Examenul radiologic baritat

_____________________________________
_____________________________________

- plus de substan de contrast


- iese din conturul gastric
- pliuri convergente
- contur (linie Hampton), colet , gura (edem
periulceros)
Nia malign - nia nu iese din contur
- pliuri ingroate, se opresc la distan
- margini neregulate - nia n lacun
Semne indirecte
UD - bulb deformat n trifoi
UG - incizur
- recese modificate
- pliu contralateral
- stenoza

Nia

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Diagnostic diferenial

_____________________________________
_____________________________________

Sindromul Zollinger Ellison


- ulcere multiple, gigante, refractare la terapie
- localizri predilecte postbulbare
- simptome asociate: diaree, esofagit
- hipergastrinemie > 1000 pg/ml
- hiperclorhidrie bazal > 15 mEq/h
- rspuns slab la stimularea cu histamin
- secreie bazal/secreie stimulat < 0,6

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56

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Dispepsia de tip ulceros
- simptome identice
- diagnostic - endoscopic - absena leziunilor ulceroase

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_____________________________________
_____________________________________

Esofagita de reflux
- formele cu pirozis
- accentuarea simptomelor n clinostatism
- cedarea rapid la antiacide
- endoscopie - prezena esofagitei
- absena ulcerului

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_____________________________________
_____________________________________
_____________________________________
_____________________________________

Afeciuni biliare, pancreatice ecografie, EDS

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Duodenita
- poate avea simptomatologie ulceroas
- endoscopic - modificri de duodenit (edem, congestie,
eroziuni)
- tratament antiulceros eficient

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Colonul iritabil
- n formele cu predominena durerilor epigastrice
- asociaz tulburri de tranzit
- lipsa modificrilor endoscopice

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Cancerul gastric

_____________________________________

- clinic - scdere ponderal


- anemie
- inapeten
- radiologic - aspectul niei
- endoscopic - aspectul ulcerului
- evolutiv - lipsa de cicatrizare la tratament corect condus
- biopsie - singurul criteriu cert
- multiple i repetate

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57

_____________________________________

Evoluie. Complicaii

_____________________________________

"once ulcer , allways ulcer" - boal cronic cu acutizri

_____________________________________
_____________________________________

Complicaii

_____________________________________

- hemoragia digestiv superioar


- insuficiena evacuatorie gastric
- perforaia
- penetraia: UD pancreas, UG lob hepatic stg; fistule
gastro colice
- malignizare: UG?

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Hemoragia digestiv superioar

_____________________________________
_____________________________________

cea mai frecvent complicaie


15% - 20% din pacienii cu ulcer
50% - 60% din totalul HDS
mortalitate - 6% - 7%
factori favorizani - consum de AINS, corticosteroizi,
anticoagulante
Clinic - hematemez / melen
- rar - hematochezie - hemoragie masiv >1000ml
- semne ale anemiei acute (paloare, transpiraii,
tahicardie, scderea TA pn la oc hipovolemic)

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Evaluarea preendoscopic

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Accesul la 1 sau 2 linii de abord venos

_____________________________________

Obligatoriu: hemoleucogram, uree, electrolii, teste


funcionale hepatice, grup sanguin, Rh, timp de
protrombin

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_____________________________________
_____________________________________

Resuscitare cu restabilirea tensiunii arteriale i volumului


intravascular (soluii cristaloide i/sau snge integral sau
mas eritrocitar)

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58

_____________________________________

Sonda de aspiraie naso-gastric

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Aspiratul nasogastric orientativ

_____________________________________

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rousngerare activ - 30%

_____________________________________

za de cafeasngerare recent - 3%

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clar 50% sngerare intermitent, duodenal


11% sngerare sever

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nu evideniaz sursa sngerrii

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Semnificaia EDS n urgen

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_____________________________________

Endoscopia urgent (precoce, imediat): primele 24 ore


de la prezentarea n serviciul de urgen

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_____________________________________
_____________________________________

Putere discriminatorie

Endoscopia n urgen + tratament endoscopic:


resngerarea
chirurgia n urgen
mortalitatea

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Evaluarea severitii HDS

_____________________________________
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Factorii clinici:

_____________________________________

Vrsta >60 ani


Comorbiditi severe (cardiace, hepatice, pulmonare,
renale, neurologice, neoplazii, septicemii)
Instabilitatea hemodinamic
Culoarea roie aspirat nasogastric
Hematemeza sau hematochezia
Sngerarea continu sau recurent

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Scorul Blatchford non endoscopic: uree, hemoglobin,


tensiune arterial sistolic, puls, melen, hematemez, sincopa,
suferina hepatic i cardiac

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59

Evaluarea endoscopic
(recurena i prognosticul Forrest, Laine, Peterson)

_____________________________________

Clasificarea Tipul de leziune


Forrest

_____________________________________

Frecvena
resngerrii
55%-90%

IA

Sngerare n jet, pulsatil,


arterial

IB

IIA

Prelingere continu,
nepulsatil a sngelui dintro leziune
Vase vizibile nesngernde

40%-55%

IIB

Cheag aderent

10%-33%

IIC

Baza de culoare neagr a


leziunii

7%-10%

Fr stigmate de sngerare

3%-5%

III

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55%-90%

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Tratamentul HDS

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Medicamentos
Endoscopic
Chirurgical

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Tratament medicamentos
(antisecretorii i substane vasoactive)

_____________________________________

Antisecretorii
Agregabilitatea plachetar, stabilitate cheag pH>6
Inhibitorii H2 nu reduc statistic semnificativ i susinut
aciditatea
IPP: bolus 80mg
+
perfuzie 8mg/or 72 ore

Meninerea constant
Inhibare rapid i
complet a pompei
a concentraiei IPP n
de protoni
snge, pH>6

_____________________________________

_____________________________________

+ dup 72 ore IPP po +/- tratament Hp

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Momentul iniierii: naintea EDS

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60

Tratamentul endoscopic

_____________________________________

Leziunile cu sngerare activ i cu risc crescut de


resngerare: IA, B, IIA, B Forrest
Tehnici de tratament:
- injectare de substane (adrenalin
1/10 000, alcool absolut)
- coagulare (termocoagulare,
electrocoagulare, laser, plasma
argon)
- mecanice (anse, clipuri, ligaturi)
Eficacitate comparabil indiferent de tehnic (alegere n
funcie de dotarea i experiena centrului)

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Biterapia > monoterapia > placebo

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Tratament chirurgical

_____________________________________

Intervenie chirurgical n urgen n HDS sever n care


EDS nu se poate efectua sau tratamentul endoscopic
hemostatic este fr rezultat

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_____________________________________
_____________________________________

n recurena HDS se recomand o nou hemostaz


endoscopic - dac nu se reuete oprirea hemoragiei intervenie chirurgical n urgen

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Perforaia

_____________________________________
_____________________________________

perforatia

- liber - cavitatea peritoneal


- acoperit (penetraie)

Factori favorizani:
persoane n vrst
consumul de AINS
fumatul
localizarea - faa anterioar a bulbului n UD
- mica curbur UG

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61

Tablou clinic
durere
- intensitate mare (lovitur de pumnal), difuz,
iradiaz n abdomenul inferior
- nsoit de stare de oc
- poate aprea n plin sntate sau n cursul
unei perioade de activitate
- acompaniat de grea, vrsturi

Examen obiectiv
- pacient anxios, ghemuit de durere, polipneic, tahicardic,
eventual subfebril
- aprare muscular ; abdomen de lemn
- dispariia matitii hepatice
- dispariia zgomotelor hidroaerice

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Examene de laborator
- VSH
- leucocitoz
- penetraie - pancreas - amilaze serice i urinare
- ci biliare bilirubinei
- hepatic - transaminazelor

_____________________________________
_____________________________________
_____________________________________
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_____________________________________

Rx abdominal simpl
- aer n cavitatea peritoneal (subdiafragmatic):
pneumoperitoneu
- examen baritat, gastroscopie - contraindicate

_____________________________________
_____________________________________
_____________________________________

Tratament : chirurgical (clasic sau laparoscopic)

_____________________________________
_____________________________________
_____________________________________

_____________________________________

Insuficiena evacuatorie gastric


cel mai frecvent prin stenoza piloric
complicaie n UD/UG (2% - 4%)
Clinic
- vrsturile - simptom principal
- zilnice/de mai multe ori pe zi /la cteva zile
- cazuri severe frecvente, explozive, n jet,
postalimentar
- atenueaza parial simptomatologia
- durerea - tipic ulceroas , cu caracter nocturn
- se asociaza cu distensie postprandial
- scderea n greutate constant, important
- saietate precoce , constipaie/diaree

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62

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Examen obiectiv
- diminuarea esutului adipos (uneori emaciere)
- deshidratare tegumente uscate, elasticitate redus
- sensibilitate epigastric
- evidenierea peristalticii gastrice
- clapotaj a jeune
Examene de laborator
- anemie
- hipoproteinemie cu hipoalbuminemie
- sindrom Darrow: tulburri ale echilibrului acido bazic
alcaloz, hipopotasemie, hiponatremie, retenie azotat

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EDS
- metoda de elecie
- de preferat s se efectueze dup golirea stomacului
- se poate aprecia
- gradului stenozei
- posibilitile terapeutice: dilatarea
endoscopic a stenozei
- se pot evidenia ulcerele gastrice/pilorice
Examen radiologic
- Rx simpl - nivel hidroaeric gastric
- Rx cu bariu dilatarea stomacului (stomac n chiuvet)
- reziduu important (fulgi de zpad)
- lipsa de pasaj duodenal
- stagnarea substanei de contrast n stomac

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Tratament medicamentos, endoscopic (dilatare), chirurgical

_____________________________________
_____________________________________

_____________________________________

PRINCIPII DE TRATAMENT
N ULCERUL PEPTIC NECOMPLICAT

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_____________________________________
_____________________________________

Scopul tratamentului n ulcerul peptic :


restabilirea echilibrului ntre mecanismele de agresiune i
aprare de la nivelul mucoasei

_____________________________________
_____________________________________
_____________________________________

Are n vedere :
ameliorarea simptomatologiei
vindecarea ulcerului peptic: eradicare Hp, neutralizarea i
inhibarea secreiei clorhidropeptice
prevenirea complicaiilor
scderea frecvenei recderilor

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63

_____________________________________

Regimul igienodietetic

_____________________________________

regimurile alimentare n ulcer sunt unice funcie de tolerana


individual
limitarea consumului de alcool i cafea datorit efectului iritativ
asupra mucoasei

_____________________________________
_____________________________________
_____________________________________

folosirea moderat a laptelui (acesta n afar de aciunea de


tamponare a aciditii, conine calciu i peptide cu efect
stimulator puternic asupra secreiei acide)

_____________________________________

prnzurile mici i repetate sunt nlocuite cu clasicele 3 mese


pe zi, ntruct alimentele ingerate tamponeaz dar i stimuleaz
secreia acid;
ntreruperea administrrii de AINS care induc ulcere adesea
silenioase care pot deveni manifeste prin complicaii inaugurale
(HDS, perforaii)

_____________________________________

evitarea fumatului!

_____________________________________

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_____________________________________
_____________________________________
_____________________________________

_____________________________________

Terapia medicamentoas

_____________________________________
_____________________________________
_____________________________________

Eradicarea Hp

Neutralizarea i inhibiia secreiei acide


Antiacide
Antisecretorii
Protectorii mucoasei gastrice

_____________________________________
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_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Medicamente folosite n tratamentul


ulcerului peptic

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Inhibitori ai aciditii
Antiacide

Dicarbocalm, Maalox, Malucol,


Rennie, Epicogel, Almagel, Ulcerotrat

Antagoniti receptori H2

Cimetidina, Ranitidina, Famotidina,


Nizatidina

Inhibitori pomp de protoni

Omeprazol, Lansoprazol, Rabeprazol,


Pantoprazol, Esomeprazol,
Dexlansoprazol

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_____________________________________
_____________________________________
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Protectori ai mucoasei

_____________________________________

Sucralfat

_____________________________________

Prostaglandine

_____________________________________

Preparate de bismut

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64

_____________________________________

Antiacidele

_____________________________________
_____________________________________

neutralizeaz aciditatea n esofag, stomac i duoden


au n compoziia lor n cantitate variabil:
carbonat de calciu
hidroxid de aluminiu
hidroxid de magneziu
bicarbonat de sodiu

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Dicarbocalm, Maalox, Malucol, Rennie,


Almagel, Ulcerotrat, Epicogel

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Antiacidele

_____________________________________

Se administreaz repetat, la 1-3 ore dup mese i seara la


culcare; de preferat sub form lichid (efect de scurt durat,
HCl se secret permanent, iar antiacidele sunt evacuate rapid
din stomac)
Efecte secundare:
- aluminiu constipaie, depleie de fosfai, neurotoxicitate la
cei cu insuficien renal
- magneziu diaree, hipermagneziemie la cei cu insuficien
renal
- carbonatul de calciu - constipaie, sindromul lapte-alcaline
(hipercalcemie, hiperfosfatemie, calcinoz renal, insuficien
renal)
- bicarbonatul de sodiu alcaloz, retenie de sodiu
Sunt puin folosite datorit modului de administrare, efectelor
secundare i eficacitii IPP

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_____________________________________

Antisecretoriile

_____________________________________

1. Antagonitii receptorilor histaminici H2

_____________________________________
_____________________________________

acioneaz competitiv cu histamina endogen blocnd


secreia de HCl

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_____________________________________
_____________________________________

comparativ, frecvena vindecrii este similar la doze


echivalente pentru aceste medicamente

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IPP sunt superiori blocanilor H2!

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65

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Antagonitii H2

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Medicament

Doz

Cimetidina

800 mg seara sau 400


mg x 2 /zi

Ranitidina

300 mg sau 150mg x 2/zi De 5 x mai activ dect


cimetidina

Famotidina

40 mg sau 20 mg x 2/zi

Nizatidina

300 mg sau 150 mg x


2/zi

Observaii

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Nu interfer cu
metabolismul
citocromului P450

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Efecte secundare ale antagonitilor H2:

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reduse
inhib receptorii H2 i din alte organe (de exemplu inim
tulburri de ritm - bradicardie i tulburri de conducere)
efect antiandrogenic ginecomastie, impoten
central, n special la vrstnici: ameeli, somnolen
sindrom moderat de citoliz
legat de citocromul P450 interfer cu unele medicamente:
teofilina, fenitoina, lidocaina
leucopenie
rash
constipaie sau diaree
cimetidina i ranitidina interfer cu alcool dehidrogenaza
(scade tolerana la alcool)

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2. Inhibitorii pompei de protoni (IPP)

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Aciune principal - blocarea la nivelul celulei parietale a


pompei responsabile de secreia de HCl (H+/K+-ATPaza)

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Primul descoperit : omeprazolul, urmat de lansoprazol,


rabeprazol, pantoprazol, esomeprazol, dexlansoprazol

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Inhibiia pompei de protoni este maxim dac se administreaz


nainte de mas

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Inhibiia secreiei gastrice acide este de 24 de ore

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Poteneaz efectul bactericid pe Hp al antibioticelor probabil


prin meninerea unui pH alcalin intragastric

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66

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Inhibitorii pompei de protoni

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Efecte secundare :
Pneumonii (atenie la vrstnici!)
Infecii intestinale (Clostridium difficile!)
Malabsorbie: vitamina B12, Fe, magneziu, calciu (cresc riscul
de osteoporoz!)
Nefrit acut interstiial foarte rar
Interfer cu alte medicamente metabolizate prin citocromului
P450 (morfina, fenitoina, clopidogrel)

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IPP i tratamentul anticoagulant (Clopidrogrel)

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- metabolism competitiv la nivelul citocromului P450

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- Clopidogrelul riscul ulcerului peptic (n special n asociere


cu aspirina), IPP eficacitatea Clopidrogrelului (Plavix)

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- Soluii: - punere n balan risc cardiovascular vs digestiv


- aministrarea la distan unul de altul (ambele au
timp de njumtire plasmatic redus)
- se prefer pantoprazolul (metabolizat doar parial
prin citocromul P450) omeprazolului

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- noi antiagregante (tienopiridine de generatia a- III-a


cu efecte secundare < asupra tractului digestiv)

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Inhibitorii pompei de protoni

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Omeprazolul 40 mg /zi
Lansoprazolul 30 mg/zi
Pantoprazolul 40 mg/zi
Esomeprazolul 40 mg/zi

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Forme de prezentare:
- Granule sau tablete cu nveli enteric
- Lansoprazolul comprimate cu dezintegrare n cavitatea oral (utile n
disfagie!)
- Pantoprazolul, Omeprazolul, Esomeprazolul forme injectabile
- Omeprazolul granule fr nveli enteric cu bicarbonat de sodiu sub
form de pulbere poate fi administrat pe sond naso-gastric

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Viitor:
Tenatoprazol: nlocuirea inelului benzimidazolic cu unul
imidazopiridinic inhibarea ireversibil a pompei de protoni
Compui potasici care vor neutraliza pompa (H, K, ATP-aza) prin
legare competitiv

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67

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Protectorii mucoasei gastrice

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Preparate de bismut coloidal

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Sucralfatul

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Prostaglandinele

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Preparate cu bismut coloidal

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DeNol - tablet de 120 mg subcitrat de bistmut coloidal

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Protejeaz structurile barierei mucoase de factori agresivi


exogeni sau endogeni prin :
- mulare pe craterul ulceros (se administrez n 2 prize cu
puin lichid nainte de mese)
- stimuleaz secreia de mucus i prostaglandine endogene
- efect bactericid pe Hp (folosit n tratament alturi de
antibiotice n unele scheme)
Efecte secundare: culoare neagr a scaunelor i a
mucoasei linguale, neurotoxicitate

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Important! folosit singur nu vindec ulcerul peptic

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Sucralfatul

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Acioneaz prin stimularea citoproteciei endogene,


mulndu-se pe craterul ulceros

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Efectul antiulceros se explic prin :


formarea unei bariere protective la suprafaa ulcerului
legarea i inactivarea pepsinei
legarea i inactivarea acizilor biliari
stimularea sintezei de prostaglandine endogene
aciune antibactericid dar nu pe Hp!

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68

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Sucralfatul

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Se administreaz de 4 ori pe zi, nainte de mese, cte 1 g


(plic)
Efecte secundare: constipaie, neurotoxicitate n insuficiena
renal, hipofosfatemie, formarea de bezoari

Important!
este la fel de eficient ca i inhibitorii H2 n tratamentul ulcerului
peptic
efecte foarte bune n :
- gastrita indus prin consum de AINS
- esofagita eroziv

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Prostaglandinele

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acioneaz direct la nivelul celulei parietale inhibnd


selectiv producerea de AMP ciclic stimulat histaminic
exercit i un efect protectiv la nivelul mucoasei
gastrice

Misoprostol (Cytotec R)
- se administreaz n 2 sau 4 prize (tb 200 mg), 800
mg/24 ore
- n special n ulcerele i eroziunile gastrice legate de
tratamentul cu AINS

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Efecte secundare: diaree, metroragii, contracii uterine

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Forme clinice de ulcere i atitudinea


terapeutic

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Se evalueaz Hp i consumul de AINS


UG i UD Hp pozitiv: eradicare Hp 10 14 zile, se
continu cu IPP pn la 4-6 sptmni UD, 8
sptmni - UG
UG: biopsii iniiale multiple, verificare endoscopic la 8
12 sptmni
Ulcerele AINS:
ntreruperea consumului de AINS sau schimbarea
cu inhibitori ai ciclooxigenazei 2 (COX2)
n situaiile n care este necesar continuarea
tratamentului cu AINS clasice se asociaz protectori
ai mucoasei (sucralfat, prostaglandine) i IPP

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69

Forme clinice de ulcere i atitudinea


terapeutic

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Ulcerele Hp negative, AINS negative


- IPP 4 sptmni UD, 8 sptmni UG

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Ulcerele refractare: lipsa vindecrii sub tratament dup


12 sptmni UG i 8 sptmni UD
- persistena infeciei Hp sau a consumului de AINS
- fumatul
- excluderea altor cauze: malignitate, sindrom Zollinger
Ellison, boal Crohn, sarcoidoz, limfom,
tuberculoz, sifilis, ischemie etc
- tratament: doz dubl IPP
eec tratament chirurgical

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Tratament chirurgical

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Numrul interveniilor chirurgicale a sczut ca urmare a


eradicrii Hp i a tratamentului (IPP, tratament
endoscopic n complicaii)

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Chirurgie laparoscopic sau clasic

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Indicaii:
- electiv: ulcerul refractar
- n urgen: HDS, perforaia, insuficiena
evacuatorie gastric

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Complicaii postoperatorii

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Ulcerul recurent
Sindromul de ans aferent
Sindromul Dumping
Diareea postvagotomie
Gastropatia de reflux biliar
Maldigestia, malabsorbia
Cancerul de bont gastric

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70

CANCERUL GASTRIC
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Date generale

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problem major de sntate n ntreaga lume


tendin de reducere a incidenei i mortalitii n rile
dezvoltate n ultimii 50 de ani
peste 750.000 de cazuri noi diagnosticate anual
650.000 de decese pe an n lume
adenocarcinomul gastric reprezint 85% din cancerele gastrice
15% sunt limfoame non Hodgkin, tumori stromale, sarcoame
(leiomiosarcoame, liposarcoame, fibrosarcoame), tumori
carcinoide sau metastatice gastrice (melanom, cancer de sn)

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Epidemiologie
extrem de frecvent n Japonia (40 de decese/100.000
locuitori/an), Europa de Est
frecven sczut n America de Nord i Europa de Vest

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n Europa - locul 3 la decese dup cancerul pulmonar i


colorectal

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brbai:femei 2:1

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vrsta de diagnostic: 65-75 de ani cu o medie de 70 de


ani la brbai i 74 de ani la femei

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distribuie: 39% stomacul proximal, 17% treimea medie,


32% antrumul i 12% ntreg stomacul

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71

Factori de risc i afeciuni cu risc


crescut n CG
1. Infecia cu H. pylori
2. Dieta
3. Leziunile precanceroase
anemia Biermer
gastrita atrofic cu metaplazie intestinal
polipii gastrici adenomatoi
ulcerul gastric
stomacul operat pentru ulcer
gastrita Menetrier
4. Factorii ereditari

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1.

Infecia cu Helicobacter pylori (Hp)


OMS a clasificat n 1994 Hp ca fiind carcinogen de ordinul I
pentru CG
induce inflamaie, apoptoz i proliferare celular epitelial
(modulat i de ali factori dietetici, etc.) cu apariia
gastritei cronice atrofice i creterea vulnerabilitii celulelor
epiteliale la diferii ageni mutageni
infecia cu Hp mai veche de 15 ani crete riscul de CG de 9
ori
serologia pentru Hp este pozitiv n 80% din CG (n special
n cele superficiale comparativ cu cele profunde)
nu este singurul factor implicat n carcinogeneza gastric (n
Africa inciden crescut pentru infecia Hp, dar frecven
sczut a CG)
studii neomogene n privina rolului tratamentului infeciei cu
Hp n prevenia CG

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2. Dieta
factori de risc
alimentele srate, conservate, afumate (conin
hidrocarburi policiclice)
nitraii - sub aciunea nitrat-reductazelor sunt
transformai n nitrii (aceast transformare este blocat
prin congelarea produselor alimentare ceea ce explic
parial scderea incidenei CG n ultimii 50 de ani)
fumatul
efect protector
dieta bogat n legume, fructe, lapte, fibre, vitamine din
grupul B i n special vitamina C ( inhib transformarea
nitrailor n nitrii )
posibil: carotenul , alfatocoferolul i seleniul

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72

3. Leziunile precanceroase
Anemia Biermer
atrofia gastric - factor favorizant pentru CG
puini bolnavi cu anemie Biermer fac CG
(supravegherea endoscopic la aceti pacieni este
controversat)
Gastrita cronic atrofic cu metaplazie intestinal
cascada precanceroas Pelayo Correa
factorii dietetici (exces de sare, nitrosamine, deficitul
de fructe, etc) i infecia cronic cu Hp determin
inflamaie local gastrit superficial atrofie
gastric (pierderea glandelor) metaplazie de tip
intestinal displazie cancer
Ulcerul gastric
UG se poate transforma n CG, procesul de
malignizare ncepe n marginile ulcerului
rol important revine infeciei Hp

Stomacul operat pentru ulcer


CG apare dup un interval liber de 15-20 ani
localizare la nivelul gurii de anastomoz sau pe ansa
intestinal
mai frecvent dup intervenie tip Billroth II comparativ
cu Billroth I (4/1)
refluxul biliar are rol important n patogenia CG
Polipii gastrici
polipii adenomatoi cu diametrul > 2 cm displazie
ulterior (ntr-un interval de aproximativ 4 ani)
carcinom in situ i cancer
tratamentul infeciei Hp asociate ar putea inhiba
carcinogeneza
Boala Menetrier
se complic cu CG n 15% din cazuri

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4. Factorii ereditari
componenta genetic
rudele de gradul I ale pacienilor cu CG dezvolt mai
frecvent gastrit atrofic (34%) i CG
pacienii cu polipoz adenomatoas familial ( FAP)
adenoame gastrice n proporie de 35-100%
CG este de 10 ori mai frecvent comparativ cu
populaia general
polipoza juvenil se nsoete de CG ntr-o proporie
de12-20%
pacienii cu cancer colorectal nonpolipozic (HNPCC)
pot avea n 10% din cazuri i CG de tip intestinal
grupa sanguin A mai frecvent afectat
mutaie CDH1 n CG ereditar difuz

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73

Clasificare

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1) Cancerul gastric precoce (tumor limitat la mucoas


i submucoas, fr metastaze ganglionare locoregionale)
I.

protruziv, polipoid formaiune proeminent sau


protruziv cu aspect nodular i suprafa neregulat
II. superficial
a. supradenivelat cu supradenivelarea mucoasei pn
la o nlime de 5 mm comparativ cu mucoasa din jur
b. superficial plat nu depete nivelul mucoasei
nconjurtoare, se identific prin aspect mai palid al
mucoasei
c. subdenivelat sau eroziv depresiune neregulat, cu
baza alb gri, cu pliuri cu aspect lrgit i care se opresc
sau nu la marginea ulceraiei
III. escavat ulcer cu margini imprecis tiate, cu mucoasa
din jur de aspect mamelonat

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2) Cancerul gastric avansat

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1. vegetant (20% din cazuri): formaiune protruziv,


exofitic, bine circumscris; mucoasa din jur are
aspect atrofic
2. ulcerat (40%): tumor vegetant n care ulceraia
este profund, baza are aspect necrotic
3. ulcerat-infiltrativ (10%) : form ulcerat, imprecis
delimitat, cu aspect infiltrativ, rigid al mucoasei din
vecintate
4. infiltrativ difuz (30%)(linita plastic): poate
prezenta la nivelul mucoasei ulceraii superficiale
sau profunde, cu margini imprecise

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Clasificarea histopatologic Lauren


1) Cancerul gastric de tip intestinal
provine din celulele gastrice care au suferit un proces
de metaplazie intestinal
evoluie ndelungat n faza precanceroas
frecvent n rile cu inciden crescut pentru CG
localizare n antrum i pe mica curbur, ulcerat
predomin la sexul masculin, la persoanele n vrst
prognostic mai bun
2) Cancerul gastric difuz
nedifereniat
provine din celule gastrice naive
aceeai frecven la ambele sexe i rspndire egal
pe glob
localizare n orice regiune gastric (inclusiv cardia),
frecvent de tip infiltrativ
prognosticul este mai sever i evoluia mai rapid

74

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Stadializare

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Tis: tumor limitat la mucoas; T1 invazia laminei propria,


T2 invazia muscularei, T3 invazia ntregului perete gastric,
T4 invazia organelor adiacente
N0 absena metastazelor ganglionare, N1 metastaze
ganglionare regionale, N2 metastaze ganglionare la distan
M0 absena metastazelor n alte organe, M1 prezena
metastazelor
CG precoce: Tis sau T1 N0M0
Stadiul 0: TisN0M0
Stadiul IA: T1N0M0
IB: T2N0M0
Stadiul II: T1N1-2M0, T2N1M0, T3N0M0
Stadiul IIIA: T2N2M0, T3N1-2M0
IIIB: T4N0-1M0
Stadiul IV: T4N2M0, T1-4N0-2M1

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Tablou clinic

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1. Cancerul gastric precoce


n 80% din cazuri este asimptomatic
simptome nespecifice, de tip dispeptic: epigastralgii
nesistematizate, senzaie de discomfort n etajul
abdominal superior, greuri
manifestrile de tip dispeptic - ntotdeauna se
investigheaz la pacienii peste 45 de ani !
poate fi precedat i/sau nsoit de sindroame
paraneoplazice
tromboflebit migratorie (semnul Trousseau)
dermatomiozit, polimiozit, neuropatii senzitive i
motorii, manifestri psihiatrice
osteoartropatie, sindrom nefrotic
keratoz verucoas i pruriginoas
achantosis nigricans

2. Cancerul gastric avansat (simptomele clinice sunt


prezente n peste 90% din cazuri)
- Simptome generale nespecifice: scdere ponderal,
inapeten (adesea selectiv pentru carne), anorexie
- Simptome orientative pentru diagnosticul de organ
durerea epigastric
- plenitudine, discomfort, arsur sau de tip ulceros n
cancerul gastric ulcerat
- postprandial, neinfluenat de antiacide sau
antisecretorii
- vrsturile alimentare: nu calmeaz durerea;
alimentele nedigerate sugereaz topografia
antropiloric
saietatea precoce (datorit lipsei de distensie a
stomacului n linita plastic)
disfagia (neoplasm eso-cardio-tuberozitar)

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75

- Simptome datorate complicaiilor


HDS melen, mai rar hematemez (10%)
abdomen acut (perforaie tumoral)
vrsturi fecaloide (fistul gastrocolic)
durere epigastric iradiat interscapulovertebral ( penetrare
n pancreas)
metastaze
hepatice (40%) icter i hepatomegalie
peritoneale ascit carcinomatoas
invazia axului splenoportal splenomegalie
pleuropulmonare tuse rebel, hemoptizii sau pleurezie
ovariene tumor Krukenberg
meningeale cu sindrom meningian
ganglionare adenopatie supraclavicular stng
(Virchow Troisier), axilar (Irish) sau infiltraie ombilical
(Sister Mary Joseph), fund de sac Douglas (Blumer)

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Examen obiectiv

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inspecie
tegumente palide sau icterice la un pacient
emaciat, cu facies suferind
semne de iritaie meningeal (n metastazele
meningeale)
formaiune care bombeaz n epigastru

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palpare
formaiune palpabil epigastric
hepatomegalie tumoral (metastaze hepatice)
ascit (carcinomatoz peritoneal)
splenomegalie (HTP segmentar)
prezena adenopatiilor supraclaviculare stngi
sau axilare

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Diagnostic paraclinic

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I)

II)

Explorarea umoral biochimic


VSH accelerat
anemie hipocrom, microcitar
fier seric sczut (pierderi cronice de snge sau HDS)
prezena sindromului bilioexcretor i de citoliz n
metastazele hepatice

Markerii serici - nespecifici

antigenul carcinoembrionar (ACE) > 5 mg/ml n 5%


din CG precoce i 35% din CG avansat

CA 19-9 inconstant crescut

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76

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III. Examenul endoscopic

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cea mai bun metod de diagnostic att pentru CG


precoce ct i pentru cel avansat

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permite prelevarea de biopsii


sunt necesare biopsii multiple (4-8)
niciodat nu se preleveaz din zona necrotic
(rezultate fals negative)
examinarea histopatologic - acuratee
diagnostic de 95-99%

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cromoendoscopia, endoscopia cu magnificaie, narrow


band imaging - cresc acurateea diagnosticului n CG
precoce

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IV. Examenul radiologic

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tipul vegetant : imagini lacunare sau defecte de


umplere care determin ntreruperea continuitii
peretelui gastric

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tipul infiltrativ: rigiditate localizat a unei poriuni a


stomacului (semnul treptei lui Haudek , semnul
scndurii pe valuri Gutmann) sau generalizat, cu
absena peristaltismului (linita plastic)
tipul excavat (meniscul ulceros): ni neregulat,
neomogen, cu baz larg de implantare, cu
rigiditate n zona supra i subjacent; pliurile
mucoasei gastrice se opresc la distan de ni, nu
converg spre aceasta

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V. Echoendoscopia (EUS)
identific profunzimea invaziei CG
deceleaz ganglionii limfatici perigastrici cu
acuratee comparabil cu CT
delimiteaz CG precoce de cel avansat:
- n CG precoce invazia este limitat la
mucoas i submucoas
- n CG avansat procesul tumoral penetreaz
toate straturile peretelui gastric

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77

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VI.

Echografia abdominal
- poate evidenia ngroarea peretelui gastric (peste 8 mm)
- neoplasmul antral n seciune sagital imagine n
cocard, de dimensiuni mari, cu zon hipoechogen
periferic groas care nconjoar o alta central
hiperreflectogen (aer gastric)
- metastaze ganglionare, hepatice, ascit carcinomatoas

VII. Computer tomografia


- acuratee superioar ecogrefiei n evaluarea:
- extensiei locale (straturile peretelui gastric invadate
de procesul tumoral)
- invadrii structurilor adiacente
- metastazelor (ganglionare, hepatice, peritoneale etc)

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_____________________________________

Diagnostic pozitiv
Circumstane de diagnostic
- simptomatologie clinic trenant de tip dispeptic,
rebel la tratament, asociat cu semne de alarm
(scdere ponderal, inapeten, etc) la pacieni peste
45 de ani
- antecedente de ulcer gastric, polipi gastrici, gastrit
Menetrier, FAP etc
- examen radiologic cu suspiciune de CG

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EDS cu examen histopatologic al biopsiei prelevate


precizeaz diagnosticul

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Bilanul extensiei: radiografie toracic, echografie


abdominal standard, echoendoscopie i/sau CT

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_____________________________________

_____________________________________

Diagnostic diferenial

_____________________________________

Ulcerul gastric benign (orice ulcer gastric necesit biopsii


multiple i control endoscopic dup terapie!)
Limfomul malign primitiv sau secundar
Tumorile gastrice benigne (leiomioame, leiomioblastoame)
Polipii gastrici
Tuberculoza gastric
Boala Crohn cu localizare gastric
Gastrita Menetrier
Cancerul pancreatic cu invazia stomacului
Cancerul de colon transvers cu invazia stomacului

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78

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Evoluie. Prognostic
diseminare prin : contiguitate, limfatic, hematogen
prognostic sever: vrsta tnr, localizarea nalt, tipul
histologic infiltrativ difuz
n Japonia la 5 ani supravieuirea este de
89% n cancerul precoce
46% n cancerele gastrice avansate
CG cu metastaze hepatice, fr tratament
supravieuire de 4-6 luni
carcinomatoza peritoneal supravieuire de 4-6
sptmni
rezecie gastric - supravieuire la 5 ani:
90% n stadiul I
50% n stadiul II
10% n stadiul III
1% n stadiul IV

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Complicaii

_____________________________________

HDS (hematemez i/sau melen) inaugural sau


n cursul evoluiei CG
perforaia
fistulele gastrocolice (invazia colonului transvers)
insuficiena evacuatorie gastric prin stenoz
mediogastric sau antropiloric care determin
sindrom obstructiv proximal sau distal
ascita carcinomatoas
metastazele: hepatice, pulmonare, ovariene,
cerebrale, osoase, etc

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Screeening i supraveghere

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_____________________________________

screeningul se efectueaz n zonele geografice cu


inciden crescut a CG
metoda: EDS cu prelevare de biopsie din orice leziune
suspect
supravegherea: individual, prin EDS, la subiecii cu
afeciuni cu risc pentru CG

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79

_____________________________________

Tratament

_____________________________________
_____________________________________

CG precoce
mucosectomia endoscopic are viz curativ
indicaii: tipul I < 10 mm, IIa < 20 mm, IIb
pentru CG precoce ulcerat se prefer intervenia
chirurgial
CG avansat
tratament chirurgical
radioterapie
chimioterapie
tratament suportiv

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Tratamentul chirurgical

_____________________________________

n funcie de localizare se efectueaz gastrectomie


parial cu anastomoz gastrojejunal sau gastrectomie
total cu anastomoz esojejunal

_____________________________________

n cazul invaziei structurile de vecintate se ncearc


exerez n monobloc fr disecia piesei

_____________________________________

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_____________________________________

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contraindicaiile tratamentului chirurgical


carcinomatoza peritoneal
metastaze multiple n ambii lobi hepatici (n cazul
metastazelor unice sau n numr redus se poate
efectua rezecia acestora sau ablaie prin
radiofrecven)

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_____________________________________

Radioterapia

_____________________________________

Are rol limitat n CG:


adenocarcinomul gastric este puin sensibil la
radioterapie
dozele ridicate au efect negativ asupra organelor
din vecintate (intestin subire, mduva spinrii)
Se poate recomanda:
radioterapie extern convenional pre i
postoperator
radioterapie intraoperatorie
radioterapie paliativ n formele hiperalgice, cu
sngerare persistent sau fenomene de insuficien
evacuatorie gastric

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80

_____________________________________

Chimioterapia

_____________________________________
_____________________________________

5 fluorouracil, mitomycin C, doxorubicin, epirubicin,


cisplatin, carmustin
Administrat pre i postoperator reduce recurenele i
prelungete supravieuirea
Anticorpii monoclonali (trastuzumab, bevacizumab,
cetuximab) i inhibitorii de tirozin kinaz studii n
desfurare (n asociere cu chimioterapia n CG
metastatic)

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Tratamentul suportiv

_____________________________________
_____________________________________

Nutriia: jejunostom, tub naso-gastric sau naso-jejunal,


gastrostom percutan endoscopic, nutriie parenteral

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Tratamentul durerii

_____________________________________

Obstrucie: tratament endoscopic (stent sau laser)

Iradiere paliativ (pentru durere, sngerare, metastaze


osoase)

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81

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LIMFOMUL GASTRIC

_____________________________________

proliferare limfoid (proliferare malign monoclonal de


limfocite B sau T) localizat la unul din segmentele tubului
digestiv, fr atingerea anterioar a ganglionilor periferici (se
exclude diseminarea secundar digestiv de la un limfom
ganglionar)
< 15% din tumorile gastrice, 2% din limfoame
majoritatea sunt limfoame non-Hodgkin cu celule B
n etiopatogenia limfoamelor MALT (mucosa associated
lymphoid tissue) este implicat infecia Hp
ali factori favorizani: boli infecioase (hepatita viral C,
virusul Ebstein Barr, HIV), boli autoimune (LES, PR, tiroidita
autoimun), sindroame de imunodeficien congenital, boli
digestive (RCUH, BC, boala celiac), terapii medicamentoase
(imunsupresoare)

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Tablou clinic

_____________________________________

Simptome puin specifice: durere epigastric (90% din


cazuri), scdere ponderal, grea, vrsturi, anemie

_____________________________________
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_____________________________________

Examenul clinic obiectiv


- la debut - poate fi normal.
- tardiv n evoluia bolii :
- inspecia - paloare
- palpare - mas tumoral epigastric
- adenopatii

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Explorri paraclinice

_____________________________________

Endoscopia digestiv superioar (EDS)


- prelevare de biopsii multiple (10-15), profunde
- toate aspectele semiologice endoscopice
- dificil de difereniat de alte leziuni (ulcer, cancer etc).
- aspectul endoscopic cel mai caracteristic este de leziune
infiltrativ + ulceraii
Examenul histologic: infiltrat n corion cu celule limfoide
de talie mic, leziuni limfoepiteliale i hiperplazie folicular
limfoid
Imunohistochimie : fenotipul B (CD20+, CD79a+)
Tehnicile de biologie molecular : trisomia 3 (50-60%),
translocarea t(11;18) (20-50%).
Echoendoscopia
- necesar pentru stadializare
- aduce informaii cu privire la gradul de infiltrare tumoral,
prezena adenopatiilor

82

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Tratament

_____________________________________

Principii :
abordare complex, multidisciplinar: gastroenterolog,
hematolog i chirurg
tratament difereniat, ntruct acest grup de neoplasme este
extrem de heterogen
iniierea tratamentului se face dup:
stabilirea tipului de limfom i a gradului de malignitate
stadializarea bolii
stabilirea particularitilor ( form localizat, difuz)
evaluarea complicaiilor

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Limfoamele cu grad redus de malignitate

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eradicarea infeciei Hp; controlul eradicrii + EDS cu biopsie;


n caz de persisten sau progresie a limfomului chirurgie

_____________________________________

chirurgie: supravieuire la 5 ani ~ 100% din cazuri

_____________________________________

radioterapia (zona gastric + ganglionii perigastrici):


alternativ la persoanele n vrst sau la bolnavii cu
contraindicaie pentru intervenia chirurgical
chimioterapie: afeciune diseminat (sfer ORL, medular,
pulmonar sau n alt esut MALT); mono sau polichimioterapie
CHOP(ciclofosfamid, doxorubicin, vincristin, prednison) n
asociere cu rituximab

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Limfoamele MALT gastrice cu grad nalt de


malignitate
- diseminri sistemice n momentul diagnosticului

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- supravieuirea la 5 ani < 46%

_____________________________________

- tratamenul de elecie chimioterapia

_____________________________________

- chirurgia - complementar n caz boal localizat sau


complicat cu hemoragii, stenoz sau perforaie

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83

84

PATOLOGIA
INTESTINULUI SUBIRE
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_____________________________________

Intestinul subire - segmentul cel mai lung al tubului


digestiv (600 cm) cuprins ntre sfincterul piloric i colon cu
dou poriuni:
- una fix retroperitoneal duodenul;
- una mobil, mezenteric jejunul i ileonul

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Intestinul subire segment complex cu numeroase


funcii: secretorie, motorie, endocrin, de aprare, rol major
n digestie i absorbie

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Tablou clinic patolgie IS

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Simptomatologie

_____________________________________

Durerea abdominal
Greurile, vrsturile (ocluzie)
Hemoragia digestiv (melen, rar hematemez, sngerri
oculte, anemie)
Tulburrile de tranzit (diaree, constipaie)

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Examen obiectiv

_____________________________________

General
faciesul peritoneal
atitudini antalgice uneori caracteristice
paloarea tegumentelor
emaciere

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85

Inspecia abdomenului :
- modificri de volum: bombare - simetric (meteorism),
- asimetric (tumori)
- imobilitatea peretelui (peritonit)
- micri antiperistaltice (ocluzie)
Palparea superficial: abdomen flasc (malabsorie); aprare
sau contractur abdominal (iritaie peritoneal)
- profund identificare formaiuni tumorale
Percuia
- hipersonoritate (meteorism)
- matitate - fix (tumori); deplasabil (ascita)
Ascultaia
- zgomote hidroaerice (ocluzii)
- linite (ileus dinamic, peritonite)

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Tueul rectal

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durerea fundului de sac Douglas (peritonita)

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identificarea unor mase tumorale abdominale

_____________________________________

absena materiilor fecale n ampula rectal (ocluzii)

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snge (ischemie intestinal)

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Examene paraclinice

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Explorarea imagistic

_____________________________________

Videocapsula de elecie
Enteroscopia permite prelevarea de biopsii + terapie
EDS (duoden), colonoscopie (ileon terminal)
Examenul radiologic abdominal pe gol
Examenul radiologic baritat (tranzit, clism baritat)
Examenul echografic
CT i/ sau RMN (enterografie CT, RMN)
Scintigrafia
Arteriografia

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86

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Explorarea umoral biochimic cuantific


anemia, funcia hepatic, renal

Testele de absorbie intestinal


puin folosite
- testul cu D-xiloza, testul de toleran la lactoz, teste
izotopice
- teste respiratorii

Explorarea imunologic - boal celiac,


limfoame, alte neoplazii

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_____________________________________

MALABSORBIA
Definiie: perturbarea absorbiei substanelor nutritive

necesare vieii
1. Anomalii ale mucoasei intestinului subire: carena
dizaharidic, deficitul de vitamin B12 i folai, sprue
nontropical, ileojejunitele nongranulomatoase,
amiloidoz, boala Crohn localizat intestinal, enterita de
iradiere, abetalipoproteinemie
2. Suprafa de absorbie improprie: sindrom de intestin
scurt, by pass-ul jejunoileal
3. Infecii: sprue tropical, boala Whipple , enteritele
infecioase acute, parazitozele intestinului subire
4. Obstrucii limfatice: limfoamele, tuberculoza,
limfangectazie
5. Boli cardiovasclare: ischemie mezenteric
6. Drog indus (colestiramina, colchicina, laxativele iritante)

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Tablou clinic
Manifestri digestive: diareea steatoree, greuri, vrsturi,
meteorism, flatulen, dureri abdominale (de tip ocluziv,
pancreatic sau vascular)
Manifestri extradigestive (sindrom carenial):
-deficit ponderal
-semne de caren vitaminic (anemie, glosit, stomatit,
nevrite, osteomalacie, sindrom hemoragipar, hemeralopie,
xeroftalmie)
-edeme careniale
-deficiene hormonale (tulburri de cretere, hipogonadism,
insuficien corticosuprarenal)

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87

Explorarea sindromului de malabsorbie (teste


mai frecvent utilizate n practic)
Teste specifice
- fier seric (N = 80 150 Pg/dl)
- folai (N = 5 -21 ng/ml)
- vitamina B 12 (N = 200 900 ng/ml); excreia urinar
de vitamina B 12 (< 8%/24h)
- dozarea n urin de acid 5-OH oxalacetic (>1,7 - 8
mg/24h)
- cultura din IS (d 105 bacterii/ml secreie jejunal)
- examen histopatologic
Teste nespecifice: calciul (N = 9 -10,5 mg/dl), albumina (N
= 4 5,2mg/dl), colesterolul (N = 150 250 mg/dl),
prezena grsimilor n scaun (normal inexistente), testul de
absorbie cu D-xiloz, teste respiratorii

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Principii de tratament

_____________________________________

Tratament etiologic: pentru fiecare cauz de sindrom de


malabsorbie n parte

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_____________________________________

Corectarea deficitelor nutriionale: calciu (1200 mg/zi),


magneziu, fier, ciancobalamin, acid folic, complex vitaminic
B, vitamine liposolubile (A, D, E, K), colestiramin, trigliceride
cu lan mediu, albumin uman

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88

_____________________________________

BOALA CELIAC
Definiie: enteropatie autoimun indus de ingestia de
gluten la persoane predispuse genetic

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Epidemiologie

_____________________________________

- frecvent n zone cu clim temperat


- prevalen: 10-30/100.000 locuitori
- n ultimii 15-20 ani crete prevalena formelor atipice
(jejunit interstiial sau preatrofic)
- afeciune genetic indus
- 8-12 x mai frecvent la rudele de gradul I
- 30 x mai frecvent la gemeni dect n populaia
general

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Etiopatogenie

_____________________________________

Predispoziie genetic:
- HLA DQ2 fixeaz preferenial o peptid din gliandin i o
prezint prin celule prezentatoare (limfocite B, macrofage,
celule dendritice) drept antigen ctre limfocitele T.

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_____________________________________
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Anomalii de permeabilitate enterocitar

_____________________________________

Gliadina acioneaz ca i antigen, contactul su prelungit cu


enterocitul conflict imun local formarea unor complexe
imune gliadin anticorpi antigliadin, care se vor fixa pe
mucoasa intestinal activarea limfocitelor killer leziune a
mucoasei pierderea vilozitilor i proliferarea celulelor
criptice

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Morfopatologie

_____________________________________

Clasificarea Marsh a leziunilor mucoasei IS (0-4)

_____________________________________
_____________________________________

Tip 0- leziune preinfiltrativ - aspectul histologic normal, dar


serologie pozitiv

_____________________________________

Tip 1- leziune infiltrativ - mucoasa este normal dar crete


numrul de limfocite intraepiteliale

_____________________________________

Tip 2 - leziune infiltrativ hiperplastic - aspectul este identic cu


tipul 1, prezentnd n plus hipertrofia criptelor cu creterea
activitii mitotice i infiltrative limfoide n corion

_____________________________________

_____________________________________

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89

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Tip 3 - leziune atrofic hipoplastic


- considerat tipic pentru boal celiac
- asociaz: atrofie vilozitar total sau subtotal + hipertrofie
criptic + hipercelularitate n lamina
proprie (limfocite,
plasmocite i eozinofile)
- atenie! - acest tip de leziune se gsete i n alte deficiene
imunologice

Tip 4 - leziune hipoplastic


- este stadiul final n evoluia bolii celiace
- se caracterizeaz prin depunere de colagen la nivelul
mucoasei i submucoasei

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Simptomatologie clinic

_____________________________________
_____________________________________

- triada diaree-steatoree-scdere ponderal


- dermatita herpetiform
- anemia feripriv sau deficitul de fier fr anemie
- hiposplenismul
- afectarea osteoarticular
- afectarea psihiatric i neurologic
- afectarea hepatic
- alte semne: talia mic, pubertatea tardiv, avorturile
spontane repetate, fertilitatea redus, hipoplazia
smalului dentar

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Afeciuni asociate n boala celiac

_____________________________________
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_____________________________________

Demonstrate statistic: diabet zaharat tip 1, deficit


selectiv Ig A, dermatit herpetiform, ciroz biliar
primitiv

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_____________________________________
_____________________________________

Posibil asociate: tiroidit autoimun, epilepsie cu


calcificri cerebrale, nefropatie mezangial cu Ig A,
poliartrit reumatoid, boal Addison,sarcoidoz

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90

_____________________________________

Diagnostic pozitiv

Gold standard: endoscopia cu biopsie din duoden distal


sau jejun + rspuns clinic la diet fr gluten
Examenul radiologic baritat al IS: tergerea desenului
mucoasei intestinale,dilatarea lumenului, ngroarea pliurilor
i segmentarea suspensiei de sulfat de bariu; poate evidenia
i complicaii
Explorare umoral biochimic: hipoalbuminemie,
hiposerinemie, hipoprotrombinemie, scderea Ca,
transaminaze crescute
Explorarea hematologic: anemie mixt macrocitar (prin
deficit cronic de acid folic) alturi de microcitoz, hipocromie
Markerii serologici: anticorpi de tip IgA, Ac antitransglutaminaz tisular i antigliandin - specificitate i
sensibilitate crescut pentru diagnostic

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Complicaii

_____________________________________
_____________________________________

Afeciuni maligne ale tractului digestiv (limfom malign


non-Hodgkin, adenocarcinom)

_____________________________________
_____________________________________

Jejunoileita ulcerativ

_____________________________________

Boal celiac colagenic

_____________________________________
_____________________________________

Tulburri endocrine, neuropsihice, leziuni osoase

_____________________________________
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_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tratament

_____________________________________

Diet fr gluten
rspuns clinic favorabil n 3-6 sptmni
rspuns morfopatologic cu restitutio ad integrum n 35 ani
excludere complet din alimentaie a finei de gru,
secar, orz i ovz
cartofii, fina de orez i de mlai sunt permise
dureaz indefinit n timp
Tratamentul medicamentos se aplic n cazurile
avansate, cnd dieta singur nu este eficace
Corticoizi per os, 10-20 mg de 2x/zi, 4-8 sptmni

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91

TUMORILE INTESTINULUI
SUBIRE

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_____________________________________
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3-7 % din tumorile tubului digestiv; 75 % sunt maligne

_____________________________________

Benigne: adenoame, leiomioame, lipoame, hamartoame,


tumori neurogenice, polipi inflamatori

_____________________________________

Maligne: adenocarcinoame, limfoame, leiomiosarcoame,


carcinoid, tumori metastatice (cel mai frecvent de la
melanomul malign)

_____________________________________

_____________________________________

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_____________________________________

Simptomatologia clinic

_____________________________________
_____________________________________

Apare tardiv

Durere abdominal: variabil

_____________________________________

Hemoragie digestiv, anemie (uneori unic simptom)

_____________________________________

Perforaie i peritonit: mai frecvent n limfom i


leiomiosarcom

Simptomatologie de tip ocluziv

_____________________________________

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_____________________________________
_____________________________________

Simptome legate de localizarea i etiologia tumorii :

_____________________________________

Sindromul icteric localizarea periampular; asociaz


colestaz, CBIH dilatate

_____________________________________

Sindromul de insuficien evacuatorie gastric n


tumorile localizate postbulbar (diagnostic tardiv,
mimeaz UD)

_____________________________________

Sindrom de ans oarb prin suprapopulare bacterian,


secundar obstruciei IS (normal 105 bacterii/ml )
Sindromul de impregnare neoplazic
finale evolutive

_____________________________________

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- n stadiile

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92

Examenul clinic obiectiv

_____________________________________
_____________________________________

Inspecia : paloare, icter sclero-tegumentar (localizare


periampular sau metastaze hepatice), unde antiperistaltice

_____________________________________
_____________________________________

Palparea: - mas tumoral abdominal cu topografie variabil


la examinri succesive datorit mezourilor largi (tumor
fantom)
- hepatomegalie tumoral metastatic
- adenopatii superficiale
- splenomegalie (n special n limfoame)

_____________________________________

Percuia : timpanism n ocluzie, ascit (n diseminri


metastatice)

_____________________________________

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_____________________________________
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_____________________________________

Explorarea imagistic

_____________________________________

Radiografia abdominal pe gol : ocluzie, perforaie

Examenul radiologic baritat al IS (n dublu contrast =


metoda Sellik): imagini lacunare, stenoze, ulceraii,
ntreruperea pliurilor

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Ultrasonografia
- modificri ale lumenului intestinal, cocard patologic
i ngroarea excentric a peretelui IS > 2mm
- cile biliare dilatate
- metastaze hepatice sau limfatice
- permite puncia cu ac fin cu prelevare de esut pentru
examen histopatologic

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_____________________________________

_____________________________________

Computer tomografia (CT) i / sau rezonana magnetic


(RM) - entero CT, entero - RM
Arteriografia: diagnostic i terapeutic (chemoembolizare)
Scintigrafia (cel mai accesibil cu I125 sau
metayodobenzylguanidin): tumori carcinoide
ERCP, MRCP n cazul obstruciei biliare
EDS, colonoscopie, enteroscopie (accesibilitate!)
Videocapsula ideal pt. explorarea IS (accesibilitate,
costuri)

_____________________________________

Atenie! Explorrile se efectueaz n funcie de


particularitatea cazului + dotarea i experiena centrului!

_____________________________________

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93

_____________________________________

Explorarea umoral-biochimic
- anemie hipocrom feripriv; teste pozitive pentru hemoragii
oculte
- sindrom de colestaz (n cazul tumorilor periampulare)
- teste hepatice modificate (metastaze)
- teste de malabsorbie
- tumori carcinoide: dozarea serotoninei i a metabolitului urinar
5 - hidroxi indolacetic

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_____________________________________

Forme clinice

_____________________________________
_____________________________________

Tumorile benigne
sunt frecvente

_____________________________________

polipi adenomatoi sau viloi, unici sau multipli, uneori n


cadrul sindroamelor polipozice:
- Peutz Jeghers (pete melanice pe buze, mucoasa bucal
i piele, asociate cu hamartoame n tot tractul digestiv, de la
stomac la rect)
- Gardner (osteoame n special mandibulare, tumori ale
esuturilor desmoide i polipi digestivi), cu tendin la
malignizare
mult mai rar se ntlnesc lipoame, fibroame, neurinoame,
leiomioame sau tumori vasculare

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_____________________________________
_____________________________________

Tumorile maligne
primitive (adenocarcinom, limfom, leiomiosarcom)
secundare (metastaze de la melanom malign)
prognostic rezervat datorit diagnosticului tardiv

_____________________________________
_____________________________________
_____________________________________

- Adenocarcinomul

- unic, schiros, stenozant


- 80% din cazuri este
diagnosticat n stadiu metastatic

_____________________________________
_____________________________________
_____________________________________

- Sarcoamele

- frecvent form vegetant


- rar infiltrativ
- frecvent - multiple
- evoluie silenioas i extrem de rapid

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94

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_____________________________________

- Tumorile carcinoide

_____________________________________

reprezint ntre 20-28% din carcinoidele digestive


peste 70% au sediul de elecie la nivelul ileonului
sunt tumori mici, frecvent multiple, schiroase, stenozante
clinic pot fi asimptomatice (70% din cazuri), sau pot
prezenta sindrom carcinoid cu manifestri:
- vasomotorii (rash cutanat)
- gastrointestinale (dureri abdominale colicative,
diaree)
- cardiopulmonare (dispnee, wheezing)

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_____________________________________

Tratament
Tratamentul chirurgical
- curativ sau paliativ
- enterectomie segmentar cu rezecie
limfadenectomie

_____________________________________
_____________________________________
_____________________________________

mezenteric pentru

_____________________________________
_____________________________________

n tumorile carcinoide
- octreotid (analog sintetic al somatostatinei): inhib eliberarea
de peptide endogene
- chimioterapia- rezultate modeste

_____________________________________

Limfoame: cur chirurgical radio i chimioterapie

_____________________________________

Terapia nutritiv de substituie dup rezeciile ntinse de IS

_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________

DIVERTICULII INTESTINULUI SUBIRE


Definiie: evaginaii parietale complete sau incomplete
congenitale sau dobndite
Simptomatologia clinic - variabil: de la forme
asimptomatice pn la complicaii (hemoragii, perforaii,
ocluzie, malabsorbie diverticuli numeroi)
Diagnosticul pozitiv este imagistic:
- radiografia pe gol imagini hidroaerice cu sediu fix
periombilical
- examenul radiologic baritat al IS: plus de substan pe faa
concav a ansei de IS
Tratament: diet, antibiotice, enterectomie parial n
complicaii
Diverticulul Mekel:
- malformaie congenital care rezult printr-o anomalie de
involuie a canalului omfalomezenteric
- asimptomatic n absena complicaiilor (atenie! poate
mima apendicita acut la copil)

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95

96

COLONUL IRITABIL
_____________________________________

Definiie:

sindrom clinic caracterizat prin asocierea


durerilor abdominale cu tulburri de tranzit n absena
leziunilor organice

_____________________________________

Date generale

_____________________________________

2009 - afeciunea gastrointestinal cea mai frecvent


uoar predominan sex feminin
afecteaz perioade lungi de timp populaia adult (40 ani);
excepional dup 60 de ani
simptomele se regsesc n afeciunile organice, deci
diagnosticul este de excludere
afeciune costisitoare, fr risc vital
evoluie
cronic,
ondulant,
numeroase
intervenii
chirurgicale nejustificate (apendicectomie, colecistectomie,
histerectomie)
costuri crescute: medicamente, absenteism etc.

_____________________________________

_____________________________________

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_____________________________________

Tablou clinic

_____________________________________
_____________________________________

tulburri de tranzit: alternan diaree/ constipaie


scaune sub form de schibale
acoperite cu mucus
diaree matinal sau la stress
emisie de mucus fr snge
dureri abdominale: frecvent cu caracter de discomfort
abdominal
balonare frecvent ameliorat de emisie de gaze
Atenie: simptomele dispar n concediu sau n perioadele de
relaxare

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97

Diagnostic pozitiv

_____________________________________

anamnez i examen clinic atent


n antecedente: stress, infecii sau abuz alimentar

_____________________________________
_____________________________________

Criterii Roma III - ndeplinite n ultimele 3 luni cu debutul


simptomatologiei cu cel puin 6 luni naintea precizrii
diagnosticului
- durere abdominal recurent sau discomfort abdominal
(senzaie neplcut, dar nu durere),
- prezent cel puin 3 zile pe lun, n ultimele 3 luni asociat cu 2
sau mai multe din urmtoarele simptome:
ameliorat de defecaie;
debut cu modificri n frecvena scaunelor;
debut asociat cu schimbri n consistena scaunelor.

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_____________________________________

Se pot asocia cu simptome frecvent ntalnite dar care nu se


ncadreaz n criteriile Roma III:
frecven anormal a scaunelor (mai puin sau mai mult
de 3 scaune pe sptmn respectiv pe zi)
form anormal a scaunelor (dure, fragmentate, mucus)
balonri
defecaie imperioas sau dificil

_____________________________________

Criteriile Roma III individualizeaz forme cu:


Diaree
Constipaie
Mixte

_____________________________________

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_____________________________________

Examenul obiectiv: NORMAL


Confirmare paraclinic - explorrile paraclinice normale

_____________________________________
_____________________________________
_____________________________________

Teste necesare pentru diagnostic diferenial


Umoral-biochimic
- hemoleucogram, serologie pentru boala celiac (Ac
antitransglutaminaz tisular)
- hormoni tiroidieni
- materii fecale - hemoragii oculte
- coproculturi, ex. coproparazitologic
- fibrinogen, proteina C reactiv i calprotectin fecal
(pentru infirmarea bolii inflamatorii intestinale)

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98

_____________________________________
_____________________________________

test respirator de toleran la lactoz sau excluderea lactozei


din diet pentru diagnosticul diferenial de intoleran la
lactoz
colonoscopia >50 de ani semne de alarm
explorarea imagistic performant (videocapsul, CT, RMN) n
cazuri selecionate, cercetare
manometrie, scintigrafie, etc

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_____________________________________

Diagnostic diferenial

_____________________________________

Prezena semnelor clinice de alarm impun explorri


suplimentare i exclud diagnosticul funcional:

_____________________________________
_____________________________________

Vrsta peste 50 de ani


Anemia
Anorexia
Febra
Melena
Rectoragiile
Tulburrile de tranzit n special nocturne, recent instalate
Folosirea recent n exces de antibiotice
Scderea ponderal
Istoricul scurt de boal
Antecedentele heredocolaterale de cancer de colon

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Diagnosticul diferenial:
- afeciuni inflamatorii (RCUH, BC)
- neoplazii
- infecii (colita pseudomembranoas, infeciile parazitare,
bacteriene)

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99

_____________________________________

Tratament

_____________________________________
_____________________________________

Afeciune funcional cronic


- 2/3 pacieni - afectare psihiatric (depresie i/sau
anxietate)
- dieta - rol important
- medicaia folosit temporar
- alteori tratament de lung durat

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_____________________________________

Relaia de ncredere medic pacient primordial!

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_____________________________________
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_____________________________________

_____________________________________

I. Tratamentul psihoterapic i psihiatric

_____________________________________
_____________________________________

1. Psihoterapia
y eficient n special n sindromul dureros
y calmarea bolnavului - esenial, cancerofobie
y evitarea strilor conflictuale

_____________________________________
_____________________________________
_____________________________________

2. Tratamentul comportamental durere i acuze


psihiatrice

_____________________________________

3.Hipnoterapia - amelioreaz durerile i tulburrile de tranzit

_____________________________________

_____________________________________

_____________________________________

4. Acupunctura

_____________________________________
_____________________________________
_____________________________________

_____________________________________

II. Tratamentul igieno - dietetic

_____________________________________

y evitarea consumului de alimente, buturi reci sau


fierbini;
y evitarea prnzurilor abundente i a consumului rapid al
alimentelor;
y orar regulat al alimentaiei;
y evitarea fumatului;
y gimnastic, not, bi calde

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_____________________________________

Dieta trebuie s fie variat, echilibrat n principii alimentare


i adaptat formei clinice.

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100

_____________________________________
_____________________________________

II. Tratamentul igieno-dietetic

_____________________________________

Dieta n forma cu predominana diareei:


y De evitat: - alimente bogate n reziduuri care baloneaz:
leguminoase, ceap, varz, ridichi, cartofi, fructe crude n
cantiti mari
- alimente grase (stimuleaz secreia de
colecistokinin): nuci, alune prjite, ciocolat
- buturi carbogazoase (baloneaz)
- alimente bogate n lactoz (lapte) sau cu
potenial laxativ: ceai, cafea, alcool, condimente

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_____________________________________

Dieta n forma cu predominana constipaiei:


y alimente bogate n fibre vegetale - cresc volumul bolului fecal,
favorizeaz evacuarea
y TRE 2 lingurie x 3/zi, crescnd doza la 2 - 3 sptmni

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_____________________________________
_____________________________________
_____________________________________
_____________________________________

Dieta n forma cu predominana balonrii


y De evitat :- alimente care produc multe gaze (banane, prune,
varz, ceap, elin, fasole)

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_____________________________________
_____________________________________

Dieta dac se asociaz deficit lactazic diet fr lapte sau


derivate din lapte

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_____________________________________

_____________________________________

III. Tratament medicamentos

_____________________________________
_____________________________________

1. Tratamentul psihotrop

_____________________________________

- sedative, anxiolitice (benzodiazepine) i antidepresive


(amitriptilina, imipramina, trimipramina)
- adjuvante utile (cu efect analgetic independent de cel
psihotrop)
- abuzul favorizeaz constipaia!

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101

_____________________________________

2. Tratamentul durerii abdominale


prinie alcoolizate (n special seara)
anticolinergice: atropina, propantelina, metilscopolamina
antispastice musculotrope:
papaverina
mebeverina (Duspatalin, Colospasmin)derivat de tip
papaverinic fr efect central - cte 1 cp dimineaa i
seara (1 cp = 200 mg)
otilonium bromid (Spasmomen)
trimebutina (Debridat, Ibutine) inhibiia musculaturii
netede intestinale reduce activitatea motorie, scade
durerea i balonarea

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_____________________________________

3. Tratamentul balonrilor i al flatulenei

_____________________________________
_____________________________________

absorbante:
crbune medicinal 5g/zi
sab simplex (dimeticon) cp = 80 mg, 1cp x 3-5 ori/zi
fermeni digestivi:
- amilaz + tripsin + lipaz (Triferment)
+ hemiceluloz, bil bovin (Cotazim, Panzcebil,
Festal, Digestal)
bromelin (Nutrizim)
+ derivate porcine de enzime pancreatice (Creon)

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4. Tratamentul SII cu predominana constipaiei


y activitate fizic
y evitarea abuzului de psihotrope
y reeducarea defecaiei (orar regulat)
y asigurarea de celulozice n diet

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

y laxative:
- de volum (mucilaginoase, hidrofile care si cresc
volumul, stimularea mecanic: metilceluloza (Colagel)
2g x2/zi, tare
- osmotice: - sulfat de magneziu n administrare unic
(5g = laxativ, 30 g = purgativ)
- magnezia usta 1 g la o administrare
- hidroxid de magneziu1 tb (300 mg)x4/zi

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102

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_____________________________________

y stimulente ale motilitii intestinale:


- bisacodyl 2-3 cp/zi (1 cp= 5 mg)
y emoliente ale bolului fecal:
- ulei de parafin 30 ml (o administrare pe zi)
y antrachinone:
- cortex frangulae( ceai de coaj de cruin)
y prokinetice ( cu 30c naintea mesei):
- metoclopramid 1 cp (10 mg) x3/ zi

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_____________________________________

_____________________________________

5. Tratamentul SII cu predominana diareei


y repaus postprandial
y excludere: dulciuri concentrate, sucuri de fructe i lapte
y medicaie:
- alcaline
- carbonat de calciu1 g x 4/zi
- argilele absorbante
- diosmectit (Smecta) 1 pachet (3g) x3/zi
- opioizi
- loperamid (Imodium) 1 cps (2 mg) x 2 - 4/zi, doza
se moduleaz n funcie de eficien, max. 12 mg/ zi, n
timpul mesei
- codeina 30 mg x 3/zi

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_____________________________________

6. Alte medicamente folosite n tratamentul SII


y Inhibitorii selectivi ai receptorilor serotoninergici (SSRIS)
- Citalopram hidrabromid (Celeza) - folosit n tratamentul
depresiei - are efect i in SII:
- amelioreaz durerea abdominal
- reduce balonarea
Inhibitori ai receptorilor serotoninergici intestinali
- Alosetron (agonist 5-hidroxitriptaminergic)
- n cazurile grave care nu au rspuns la terapie
convenional
- determin diminuarea tranzitului, a nevoii imperioase
de defecaie ct i a durerii abdominale

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_____________________________________
_____________________________________
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_____________________________________

Atenie: risc de colit ischemic!

_____________________________________

103

y Tegaserolul (Zelnorm) este agonist parial


5-hidroxitriptaminergic: stimuleaz peristaltica, reduce
hipersensibilitatea visceral, diminueaz durerea i
discomfortul abdominal, normalizeaz funcia intestinal
y Lubiprostonul (Amitiza): determin creterea motilitii
intestinale
y Rifaximina (Normix) (1 cp =200) 400mg x3/zi, 10 zile;
antibiotic non sistemic, acioneaz la nivelul tubului digestiv
pe bacteriile gram pozitive i gram negative aerobe i
anaerobe
Probiotice
- metanalize pe trialuri mari de pacieni
- probiotice (n special bifidobacterii)
- combinaii de probiotice - diminuarea persistenei
simptomelor
Colon Health - lactobacillus gasserie (absorbia i digestia
lactozei)
- bifidobacterium bifidum (combatere balonare,
diaree i constipaie)
- bifidobacterium longum (rol n imunitate)

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104

BOLILE INFLAMATORII
INTESTINALE
_____________________________________
_____________________________________

Definiie: afeciuni inflamatorii cronice ale tractului


digestiv, fr o etiologie cert, cu substrat patogenic imun,
definite pe baza unor criterii clinice, biologice, endoscopice,
i morfologice
BII includ dou entiti distincte: rectocolita ulcerohemoragic (RCUH) i boala Crohn (BC), la care se
adaug colita microscopic (colita colagenic i
limfocitar)
n 10% din cazuri RCUH nu pot fi difereniat de BC pe
baza criteriilor clinice, radiologice, endoscopice sau
morfopatologice.

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_____________________________________

RECTOCOLITA ULCEROHEMORAGIC

_____________________________________

Definiie

_____________________________________

_____________________________________
_____________________________________

_____________________________________

boal inflamatorie cronic intestinal idiopatic care


intereseaz rectul i se extinde proximal colonic fr a
depi valva ileo-cecal

_____________________________________
_____________________________________
_____________________________________

leziunile sunt continui, fr a fi separate de mucoas


normal, procesul inflamator fiind limitat la mucoas i
submucoas

_____________________________________
_____________________________________
_____________________________________

evoluia clinic este cronic, cu exacerbri i remisiuni

_____________________________________
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105

Epidemiologie

_____________________________________

afeciune ubicvitar, inciden: 2-10 la 100.000 locuitori,


prevalen: 35-120 la 100.000 locuitori n ariile geografice
cu frecven mare (America de Nord, nord-vestul Europei)

_____________________________________

prevalen redus n Europa central i de sud-est, Asia,


Africa, America de Sud

_____________________________________

afecteaz att femeile ct i brbaii (cu o uoar


predominen la sexul feminin)

_____________________________________

_____________________________________
_____________________________________

_____________________________________

_____________________________________
_____________________________________

are dou vrfuri de inciden: 15-35 i 55-65 ani

_____________________________________

n ultimii ani se constat tendin de stabilizare a frecvenei


RCUH, comparativ cu BC care prezint inciden n
cretere

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_____________________________________

_____________________________________

Etiologie

_____________________________________

Factori genetici (agregare familial)

_____________________________________
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Dieta: alergia la proteinele din laptele de vac, consumul de


dulciuri rafinate, alptarea insuficient la sn, prelucrarea
termic excesiv etc

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Factori infecioi: E. coli

_____________________________________
_____________________________________

Consumul de contraceptive orale

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Fumatul, ca i apendicectomia au rol protectiv

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Fiziopatologie

_____________________________________
_____________________________________

antigenele luminale (bacteriene, alimentare etc.) vin n contact


cu macrofagele epiteliale care au 2 roluri:
- celule prezentatoare de antigen limfocitelor CD4 helper
- eliberarea de Il1(ce stimuleaz activitatea limfocitelor T)
i alte citokine inflamatorii: Il2, Il4, TNF etc
n RCUH rspunsul imun este de tip Th2 (caracteristic
rspunsului umoral cu producere de anticorpi)
un rol important l are factorul de transcripie nuclear NF B
prin care este stimulat producia citokinelor pro-inflamatorii i
moleculelor de adeziune celular (ICAM i VCAM)
chemokinele determin recrutarea a numeroase celule
circulante (mononucleare, granulocite etc) la locul inflamaiei
care elibereaz prostaglandine, leucotriene, proteaze, radicali
liberi de oxigen, oxid nitric ce vor amplifica distrugerea tisular

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106

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Tablou clinic

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I. Manifestri digestive:
- episoade de diaree cu snge, mucus i puroi asociate cu
dureri abdominale, crampe, tenesme, durere la palpare pe
traiectul colonului i n hipogastru
- n puseu, de obicei 3-10 scaune/zi, n formele severe numai
emisii de snge, mucus i puroi

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II. Manifestri extradigestive

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Manifestri osteo-articulare: sacroileit, artrit, osteoporoz


Manifestri cutanate: eritem nodos, pyoderma gangrenosum,
sindrom Sweet, psoriazis, vitiligo, erupii urticariene, degete
hipocratice, acrodermatit enteropatic
Manifestri oculare: uveit, irit, episclerit
Manifestri hepato-biliare: steatoz hepatic, colangita
sclerozant primitiv, amiloidoz hepatic
Manifestri renale: pielonefrite, litiaz renal, amiloidoz
renal
Manifestri trombo-embolice

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Diagnostic de laborator

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Anemie: hipocrom, feripriv (fier, feritin ) sau de tip


inflamator (feritin )
Sindrom inflamator: creterea VSH-ului, leucocitoz, creterea
proteinei C reactive, fibrinogenului, 2 globulinelor
Trombocitoz
n formele severe (megacolon toxic) apar dezechilibre
electrolitice: hiponatremie, hipopotasemie, hipocloremie
Prezena citolizei i colestazei atrag atenia asupra unei
patologii hepato-biliare asociate
Anticorpii anti citoplasmatici neutrofilici perinucleari (p
ANCA) - 70% din pacienii cu RCUH
Markeri ai inflamaiei identificai n materiile fecale:
calprotectina

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107

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Colonoscopie
tipic: afectarea rectului, extensie proximal la nivelul colonului,
caracterul continuu al leziunilor endoscopice
n puseu mucoasa plnge cu snge, este friabil, cu ulceraii
superficiale, eritem difuz, pierderea desenului vascular,
prezena de mucus i puroi n lumen
n remisiune mucoas cu desen vascular ters sau absent,
sngernd la atingere, pseudopolipi inflamatori
n forme cronice pseudopolipi
Biopsia obligatorie pentru diagnostic
- infiltrat inflamator cu PMN limitat la nivelul mucoasei
- prezena abceselor criptice (caracteristice n faza acut)
- mucoas hiperemic, edemaiat, exulcerat
- n formele cronice pseudopolipi inflamatori

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Clisma baritat

_____________________________________

- util n formele cronice, pentru evaluarea extinderii leziunilor

- aspect granular al mucoasei, tergerea haustrelor (edem)

_____________________________________
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_____________________________________

- spiculi marginali, aspect de buton de cma (ulceraii)

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- pseudopolipi (imagini lacunare)

_____________________________________

- ileit de reflux (backwash ileitis)

_____________________________________
_____________________________________

- forme cronice - haustre disprute, calibru diminuat,


distensibilitate redus, aspect de microcolie

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Forme clinice

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Evolutive
- acut fulminant
- cronic intermitent
- cronic continu (mai rar)

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Extensie: - proctite (46%; 50% evolueaz progresiv)


- colite stngi (17%)
- pancolite (37%)

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108

Forme clinice - severitate


Factori clinico-biologici (clasificarea Truelove i Witts)
RCUH uoar: 1-3 scaune/zi, prezena sngelui intermitent
n scaun; fr febr, tahicardie, anemie; VSH<30 mm/h
RCUH moderat: criterii intermediare ntre forma uoar i
sever
RCUH sever: >6 scaune/zi, prezena sngelui la
majoritatea emisiilor de fecale, temperatura >37.5C,
frecvena cardiac >90/min, scderea hemoglobinei cu
>75% fa de normal, VSH>30 mm/h
RCUH fulminant: >10 scaune/zi, prezena sngelui la toate
emisiile de fecale, temperatura >37.5C, frecvena
cardiac>90/min, scderea hemoglobinei cu >75% fa de
normal, VSH>30 mm/h, transfuzii de snge

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Forme clinice - severitate

_____________________________________
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Factori endoscopici (scorul Mayo)


0: mucoas normal
1: eritem, granularitate, diminuarea desenului vascular,
friabilitate
2: la fel ca 1, n plus eroziuni i dispariia desenului
vascular
3: la fel ca 2, n plus ulceraii i sngerri spontane

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Diagnostic pozitiv

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_____________________________________
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Clinic

_____________________________________

Colonoscopie

RCUH

Radiologie

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Ex. histopatologic

_____________________________________

Laborator

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109

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Diagnostic diferenial

Colitele infecioase (Shigella, Entamoeba histolitica, Campylobacter,

_____________________________________

Giardia, Esherichia coli, Criptosporidium, Mycobacterium avium,


Citomegalovirus, Histoplasma, Treponema pallidum,Herpes simplex,
Chlamydia trachomatis)

_____________________________________

Colita pseudomembranoas (Clostridium)


BC
Hemoroizii i fisurile anale
Cancerul colo-rectal
Polipii colo-rectali
Diverticuloza colonic
Colita ischemic (rect indemn!)
Colita de iradiere
Colita colagenic i limfocitar
Colonul iritabil

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Complicaii

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Megacolonul toxic

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Perforaia

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Hemoragia digestiv inferioar

_____________________________________

Cancerul colo-rectal

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Megacolonul toxic

_____________________________________

Manifestri sistemice - minim 3 din urmtoarele: febr > 380C,


tahicardie > 120 bti/min, globule albe > 10500/mm3, anemie
i toxice (minim 1): deshidratare, diselectrolitemie,
hipotensiune arterial, tulburri mentale

_____________________________________

_____________________________________

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_____________________________________

Factorii precipitani: hipokaliemia, utilizarea anticolinergicelor


i opiaceelor, explorrile endoscopice

_____________________________________

Examenul obiectiv evideniaz abdomen destins, meteorizat,


sensibil la palpare, cu dispariia zgomotelor hidro-aerice

_____________________________________

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110

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Megacolonul toxic

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_____________________________________

Radiografia abdominal simpl


colonului transvers > 6 cm

arat

dilatarea

_____________________________________
_____________________________________

Explorarea colonoscopic
contraindicate!

sau

irigografic

sunt

_____________________________________
_____________________________________

Tratament medical conservator (repaus digestiv, sond


de aspiraie naso-gastric, corecie hidro-electrolitic,
antibiotice cu spectru larg, profilaxia manifestrilor
tromboembolice, corticosteroizi i.v. sau ciclosporin sau
anti-TNF); n caz de eec colectomie n urgen

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Cancerul colo-rectal

_____________________________________

Factori de risc:
durata evoluiei bolii (riscul neoplazic apare dup 8 ani de
evoluie i crete exponenial dup 20 de ani)
extensia bolii (pancolitele prezint riscul cel mai mare)
asocierea colangitei sclerozante primitive
antecedente familiale de CCR
vrsta tnar la debut
Supravegherea colonoscopic
colonoscopie + cromoendoscopie, cu biopsii multiple dup 8
ani de evoluie
absena displaziei colonoscopie la 2 ani sau anual dac
evoluia bolii este > 20 de ani
displazie sever colectomie
displazie uoar tratament endoscopic (polipectomie,
mucosectomie) i intensificarea supravegherii colonoscopice la
3-6 luni

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Tratament

_____________________________________

Scop: tratarea inflamaiei, dispariia simptomelor, inducerea i


meninerea remisiunii, prevenirea cancerului colo-rectal

_____________________________________

Dieta

_____________________________________

n formele fulminante se suprim alimentaia oral, se


administreaz nutriie parenteral
n puseele severe se utilizeaz o diet hipercaloric (2500-3000
calorii/zi), hiperproteic (100-150 grame proteine/zi), bogat n
sruri minerale i vitamine
vor fi evitate alimentele care produc reziduri, fructele i
legumele crude, laptele, sucurile de fructe, brnzeturile
fermentate, grsimile prjite, carnea prjit sau afumat,
dulciurile concentrate, murturile, condimentele
sunt permise supele de carne i perioare, pinea alb, cartofii
fieri, brnzeturile nefermentate, carnea, unca, oule, budinci,
paste finoase
dieta restrictiv n perioadele de remisiune ale bolii nu previne
reactivarea inflamaiei

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111

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Clase de medicamente

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Aminosalicilaii
Corticosteroizii
Agenii imunomodulatori
Terapia biologic (anti TNF)
Alte clase de medicamente: antibiotice, probiotice

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Aminosalicilaii

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Preparate de acid 5-aminosalicilic (5-ASA)


n tratamentul de inducie n formele uoare i moderate
n tratamentul de ntreinere al RCUH

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Salazopirina
este format din sulfapiridin (molecul lipsit de efecte
terapeutice) i 5 - ASA, legate printr-o legtur azo
tablet de 500 mg; doza 2 4 g/zi
efectele secundare ale salazopirinei:
- dependente de doz i de rata de acetilare
(greuri,vrsturi, cefalee, malabsorbie de folai)
- independente de doz (anemie hemolitic, neutropenie,
infertilitate masculin, erupii cutanate, hepatit colestatic)

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Aminosalicilaii

_____________________________________
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Noile preparate de 5-ASA: mesalazin (salofalk,


pentasa) au avantajul c sunt lipsite de efectele
secundare ale sulfapiridinei i sunt disponibile i sub
form de preparate topice (supozitoare, clisme)
pentru tratamentul formelor distale
Combinaia administrrii rectale i orale de
mesalazin are eficacitate superioar n inducerea i
meninerea remisiunii n formele distale de RCUH
comparativ cu administrarea izolat per os sau topic

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112

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Corticosteroizii

au multiple aciuni antiinflamatorii i imunsupresive

se utilizeaz n tratamentul de inducie al formelor severe


de RCUH, n doz de 40-60 mg/zi, cu scderea
progresiv a dozelor

_____________________________________
_____________________________________

pot fi administrai sistemic (p.o. prednison, medrol sau


i.v solumedrol, dexametazon, hidrocortizon) sau n
preparate topice (clisme)
efectele secundare multiple (Cushing, acnee, hirsutism,
hipertensiune arterial, diabet zaharat, osteoporoz etc)
le limiteaz utilizarea pe termen lung

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nu pot fi folosii n meninerea remisiunii

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Agenii imunomodulatori

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sunt folosii n tratamentul de ntreinere, n formele


cortico-dependente, cortico-rezistente sau n cazul
pacienilor care au contraindicaii pentru corticosteroizi

_____________________________________
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Azatioprina i 6-mercaptopurina se folosesc n doze


de 2,5 respectiv 1,5 mg/kg/zi

efecte secundare: leucopenie, pancreatit, reacii


alergice, complicaii infecioase, neoplazii

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Terapia biologic

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Infliximabul (anticorp anti TNF) i-a dovedit eficiena


n inducerea i meninerea remisiunii n RCUH

_____________________________________
_____________________________________

Indicaii: formele moderate i severe, cortico-refractare


sau corticodependente
Se administreaz 5 mg/kgc n perfuzie i.v. (flacoane de
100 mg) n sptmnile 0, 2, 6 i apoi la fiecare 8
sptmni

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113

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Alte clase de medicamente

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Antibioticele sunt utile doar n cazul complicaiilor


(megacolon toxic). Nu i-au dovedit eficacitatea n
tratamentul de rutin al puseelor de RCUH

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_____________________________________

Probioticele (Escherichia coli nissle i lactobacili)


- i-au dovedit eficacitatea n prevenirea recurenelor bolii
- pot fi folosite ca alternativ sau complementar tratamentului
cu aminosalicilai n terapia de ntreinere
- nu au eficacitate n puseele de activitate ale RCUH

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_____________________________________
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_____________________________________

Plasturii cu nicotin (fumatul are rol protectiv n RCUH!)


sunt utili n faza activ a bolii dar nu au efect n meninerea
remisiunii. Nu sunt utilizai n practica clinic.

_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tratamentul formelor clinice de RCUH

_____________________________________

1. Forme severe i fulminante

_____________________________________

- reechilibrare hidroelectolitic, alimentaie parenteral


- profilaxia trombembolismului (heparine cu greutate
molecular mic)
- n forme toxico-septice antibioterapie (metronidazol,
cefalosporine, ciprofloxacin)
- corticoterapie (Hidrocortizon i.v. 300-400mg/zi, apoi n
caz de evoluie favorabil - Prednison p.o. 1 mg/kg/zi cu
reducerea progresiv a dozelor cu 5 mg/sptmn)
- evoluie nefavorabil: Ciclosporin 4 mg/kgc/zi iv sau
terapie biologic (Infliximab); dac inducerea remisiunii s-a
obinut cu terapie biologic, Infliximabul va fi administrat la 8
sptmni ca tratament de meninere
- lipsa ameliorrii sub tratament medical proctocolectomie

2. Forme medii:
- Prednison p.o. 40 - 60 mg/zi, cu scderea progresiv a dozelor
(cu 5 - 10 mg/spt)
- se asociaz mesalazin 3- 4 g/ zi care va rmne ca tratament
de ntreinere dup oprirea corticoterapiei
- n formele corticorezistente (nu rspund la corticoterapie),
corticodependente (reactivarea bolii la ncercarea de reducere
sau ntrerupere a corticoterapiei) sau n caz de contraindicaii la
corticoterapie se administreaz Infliximab i/sau ageni
imunmodulatori (azatioprin, 6-mercaptopurin)
3. Forme uoare
- Mesalazin p.o. 1,5-2 g/zi sau Salazopirin p.o. 3-4 g/zi
3. Forme distale (rectosigmoidiene):
-microclisme sau supozitoare cu Mesalazin sau Budesonid
-preparatele topice sunt superioare tratamentului p.o, iar
tratamentul combinat topic i p.o. este superior comparativ cu
fiecare n parte

114

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Tratamentul chirurgical

_____________________________________

Indicaii:
x complicaii acute: megacolon toxic, perforaie, hemoragie
digestiv sever, complicaii septice
x forme non-responsive la tratament medical, cronice continui
x detectarea displaziei severe, profilaxia malignizrii

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Se practic proctocolectomie total cu ileo-anastomoz i


crearea unui rezervor ileal (pouch)

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_____________________________________

BOALA CROHN

_____________________________________
_____________________________________

Definiie

_____________________________________

afeciune inflamatorie cronic idiopatic ce poate interesa


segmentar i discontinuu orice segment al tractului
digestiv, localizndu-se cel mai frecvent la nivelul valvei
ileo-cecale
procesul inflamator are caracter transmural, se poate
extinde pn la nivelul seroasei i a structurilor pericolice,
ducnd la formarea de abcese, stenoze i fistule

_____________________________________

Localizare

_____________________________________

- ileon terminal - 30%


- ileo-colonic > 50%
- colonic
- orice segment al tubului digestiv (inclusiv esofag, stomac,
duoden, apendice)

_____________________________________

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Epidemiologie

_____________________________________

arii cu inciden i prevalen crescut (1-6 la 100.000


locuitori, respectiv 10 100 la 100.000 locuitori ) : America de
Nord, nord vestul Europei
arii cu frecven redus : Africa, Asia, America de Sud, centrul
i sudul Europei

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afecteaz egal ambele sexe (cu uoar predominen la sexul


feminin)

_____________________________________
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este diagnosticat cel mai frecvent n jurul vrstei de 30 de


ani; al doilea vrf de inciden la 60-65 ani

_____________________________________
_____________________________________

exist o tendin de cretere a incidenei BC, fapt constatat i


n Romnia

115

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_____________________________________

Etiologie

_____________________________________

Factori genetici
- agregabilitate familial
- concordan la gemenii monozigoi
- mutaiia genei NOD 2
Factori dietetici: dulciuri rafinate, alimentaia srac n
legume i fructe proaspete, oxidul de titaniu
Factori infecioi: Mycobacterium paratuberculosis, virusul
rujeolic i Lysteria monocytogenes

Ali factori: fumat, contraceptive orale, antiinflamatorii nonsteroidiene, statusul socio-economic ridicat

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Fiziopatologie

_____________________________________
_____________________________________

fiziopatologia BC este asemntoare RCUH

_____________________________________

predomin rspunsul imun de tip Th1 (celular, reacii de


hipersensibilitate ntrziat)

_____________________________________
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_____________________________________

se elibereaz citokine inflamatorii: IFN, Il2, Il12, Il18, cu


creterea produciei de TNF i NF-B

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Morfopatologie

_____________________________________

Macroscopic

_____________________________________

procesul inflamator intereseaz discontinuu i asimetric orice


segment al tractului digestiv
rectul este de obicei indemn dar pot exista leziuni anale
(abcese perianale, fisuri, fistule)
peretele intestinal este ngroat i indurat segmentar
ca urmare a caracterului transmural al inflamaiei ansele
intestinale devin stenotice, cu tendin la aglutinare; ulceraiile
profunde se pot extinde n structurile adiacente determinnd
fistule
mucoasa prezint ulceraii aftoide ( ulceraii superficiale, de
mici dimensiuni, bine delimitate, nconjurate de halou hiperemic)
n evoluie ulcerele se mresc, conflueaz, au traiecte
lineare i serpinginoase, se extind pn la tunica muscular i
delimiteaz arii de mucoas normal, crend aspectul de piatr
de pavaj caracteristic BC

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116

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Morfopatologie

_____________________________________

Microscopic

_____________________________________

caracterul transmural al inflamaiei i granulomul sarcoid

_____________________________________
_____________________________________

infiltratul limfoplasmocitar asociat cu fibroz se ntlnete n


toate straturile peretelui intestinal

_____________________________________
_____________________________________

granulomul de tip sarcoid este format din celule epitelioide i


celule gigante multinucleate nconjurate de un inel periferic de
limfocite

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_____________________________________

Tablou clinic
Simptome intestinale:
- diareea
- durerea abdominal : localizat n flancul sau fosa iliac
dreapt sau difuz
- rectoragiile sunt rar ntlnite
- leziuni perianale : modificri cutanate perianale, leziuni de
canal anal, abcese i fistule

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_____________________________________
_____________________________________

Manifestri sistemice: febr, scdere ponderal, astenie,


alterarea strii generale

_____________________________________

Examenul obiectiv poate evidenia leziunile cutanate orale i


perianale, paloare, denutriie, mase tumorale palpabile,
abcese, traiecte fistuloase

_____________________________________

_____________________________________

_____________________________________
_____________________________________

_____________________________________
_____________________________________

Manifestri extraintestinale

_____________________________________

Manifestri articulare: artrit, spondilit ankilozant,


osteoporoz
Manifestri cutanate: leziuni perianale (eritemul perianal,
skin tag, ulcere aftoide, abcese sau fistule
perianale);ulceraii aftoide bucale; inflamaie cutanat
granulomatoas; eritem nodos; pyoderma gangrenosum
Manifestri oculare: episclerit , sclerit, uveit
Manifestri digestive: colangit, litiaz biliar
Manifestri genito-urinare: litiaz renal, amiloidoz, fistule
Manifestri trombo-embolice
Manifestri datorate malabsorbiei

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117

Explorri biologice

_____________________________________

Anemie, prin mecanisme multiple: inflamaie, pierderi de snge,


defit de absorbie a fierului i vitaminei B12
x Sindrom inflamator (VSH, leucocitoz, proteina C reactiv etc.)
x Trombocitoz
x Hipoalbuminemie
x Teste de citoliz i colestaz modificate n cazul asocierii
patologiei hepatice
x Dezechilibre hidro-electrolitice n formele severe
x Anticorpii anti Saccharomyces cerevisiae (ASCA) pozitivi sunt
utili pentru diferenierea BC de RCUH
x Teste care evideniaz malabsorbia : determinarea grsimilor n
scaun, testul Schilling, C14 taurocolat, testul respirator cu H2 etc
x Testele genetice (mutaiile la nivelul genei NOD2) sunt folosite
n cercetare i nu n practica clinic
x

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_____________________________________

Explorarea endoscopic

_____________________________________

Colonoscopia
- leziuni aftoide, ulceraii adnci, liniare
- aspect de piatr de pavaj
- prezena unor zone de stenoz inflamatorie
- fistule
- arii de mucoas normal
- biopsie: granulom, infiltrat limfoplasmocitar

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_____________________________________
_____________________________________

EDS pentru evaluarea tractului digestiv superior

_____________________________________

Explorarea intestinului subire:


- Videocapsula metoda de elecie dac nu se suspicioneaz
prezena stenozelor
- Enteroscopia: permite prelevarea de biopsii

_____________________________________
_____________________________________
_____________________________________

_____________________________________

Clisma baritat
-

_____________________________________

_____________________________________

mult mai puin fidel dect endoscopia


aspect de pietre de pavaj, ulceraii lineare
ngustarea lumenului, zone de stenoz
pseudodiverticuli
fistule
n ileita terminal pe marginea stng a cecului se poate
vedea amprenta unei mase ganglionare; cecul este intolerant
i nu se opacifiaz (semnul saltului)

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118

_____________________________________

Ecografia

_____________________________________

- ngroarea peretelui intestinal


- zone de stenoz sau dilatare

_____________________________________

Computer tomografia, rezonana


magnetic

_____________________________________

- ngroarea peretelui, adenopatii inflamatorii, fistule, abcese


- Entero CT, Entero-RM folosite n special n leziunile
localizate la nivelul intestinului subire

_____________________________________

_____________________________________

_____________________________________

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_____________________________________

Clasificarea Montreal
Vrsta n momentul
diagnosticului
Localizare

Forma clinico-evolutiv
(fenotip)

A1: < 17 ani


A2 >17 - 40 ani
A3: > 40 ani
L1: ileal
L2 :colonic
L3: ileocolonic
L4: tract digestiv superior (se
adaug L1-L3 cnd afectrile
coexist)
B1 nonstenozant, nonpenetrant
B2 stenozant
B3 penetrant
p : se adaug formelor B1-B3
cnd coexist boal perianal

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Diagnostic diferenial

_____________________________________
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_____________________________________

- colita ischemic
- colita de iradiere
- RCUH
- neoplasmul de colon
- apendicita acut
- tuberculoza intestinal
- limfomul intestinal
- boala Behcet
- afeciuni genitale

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119

Diagnostic diferenial RCUH - BC

_____________________________________

Clinic
RCUH: diaree, rectoragii
BC: diaree, dureri abdominale, febr, mase abdominale
palpabile, fistule i abcese perianale
Colonoscopic
- RCUH: leziuni continui, nu exist arii de mucoas
normal n zona inflamat, mucoas granular, friabil,
ulceraii, pseudopolipi
- BC: leziuni discontinui i asimetrice, ulcere aftoide,
aspect de piatr de pavaj, stenoze
Histologic
- RCUH: inflamaie limitat la muscularis mucosae, criptite,
abcese criptice, ramificarea i scurtarea criptelor
- BC: inflamaie transmural, granulom de tip sarcoid, fisuri

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Diagnostic diferenial RCUH - BC

_____________________________________

Radiologic
- RCUH: leziuni continui, spiculi laterali, scurtarea i
dehaustrarea colonului
- BC: leziuni segmentare, interesare intestin subire, piatr
de pavaj, stenoze, fisuri, fistule, abcese
Serologic
- RCUH: ANCA
- BC: ASCA
Complicaii
- RCUH: megacolon toxic, perforaie
- BC: stenoze, abcese, fistule
Tratament chirurgical
- RCUH: colectomia total are viz curativ
- BC: tendin la recidiv postoperatorie

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Complicaii

_____________________________________

_____________________________________

Abcese
Fistule
Stenoze
Manifestri perianale
Cancer colo-rectal

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120

_____________________________________

Tratament

_____________________________________

Scop

_____________________________________

Clasic: inducerea i meninerea remisiunii, ameliorarea


simptomatologiei
n prezent:
- deep remission: remisiune clinic, biologic,
endoscopic (vindecarea mucoasei) i histologic
- schimbarea cursului evoluiei bolii (mpiedicarea evoluiei
spre comportament penetrant sau stenozant)
- scderea numrului interveniilor chirurgicale
- scderea numrului de zile de spitalizare
- creterea calitii vieii

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Tratament

_____________________________________

Dieta: aceleai principii ca n RCUH


Tratament medicamentos: corticosteroizii, agenii

_____________________________________

imunmodulatori, terapia biologic, derivaii 5-ASA,


antibioticele

Tratament endoscopic: dilatarea stenozelor


Tratament chirurgical
- complicaii intestinale (ocluzii, abcese, perforaie)
- eec al terapiei medicale
- manifestri extraintestinale (artrit, uveit, pyoderma)
rezecii segmentare ct mai conservatoare, precum i
tratamentul specific al complicaiilor (abcese, fistule)

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Corticosteroizii

_____________________________________

se folosesc pentru inducerea remisiunii n BC


se administreaz intravenos (n formele severe) sau per
os 40 60 mg/zi, cu scderea progresiv a dozelor
nu pot fi utilizai pentru meninerea remisiunii
efecte secundare multiple (de la cele cosmetice pn
la creterea riscului de infecii severe)
budesonidul
- corticoid care se metabolizeaz la primul pasaj hepatic
- acioneaz la nivelul ileonului i colonului drept
- are efecte secundare sistemice reduse
- tablete de 3 mg, se administreaz 9 mg/zi

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121

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Agenii imunomodulatori

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_____________________________________

azatioprin (2,5 mg/kg/zi), 6 mercapto-purin (1,5


mg/kg/zi), metotrexat (15-25 mg/sptmn)
utili n meninerea remisiunii
se asociaz corticoterapiei pentru reducerea dozelor de
cortizon
prevenirea imunogenitii la pacienii cu terapie biologic
asocierea imunmodulatorului cu Infliximab (comboterapia)
este superioar comparativ cu monoterapia la pacienii
naivi (studiul Sonic)
tratament eficient pentru nchiderea fistulelor
efectele secundare prezentate la RCUH

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Derivaii 5-ASA

_____________________________________

eficacitate limitat n BC
pot fi folosii n formele uoare sau medii de BC cu afectare
colonic

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_____________________________________

Antibioticele
se folosesc n tratamentul formelor moderate de BC, n
cazul leziunilor perianale, abceselor i fistulelor, pentru
profilaxia recidivelor postoperatorii
se utilizeaz metronidazolul, singur sau n asociere cu
fluorochinolone (Ciprofloxacin 1g/zi)

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Agenii biologici

_____________________________________

Anticorpi monoclonali anti-TNF


Infliximab prima generaie (proteine murine), aprobat din
1998 n tratamentul BC
Adalimumab - anti-TNF alctuit 100% din proteine
umane
Certolizumab - anticorpi monoclonali pegylai umanizai
Eficacitate similar indiferent de agentul biologic folosit!
Indicaii: formele moderat severe de BC i BC fistulizant
Sunt utili att n inducerea ct i n meninerea remisiunii
Posologie:
Infliximab (1fiol = 100 mg) se administreaz n perfuzie
intravenoas 5 mg/kgc la 0, 2, 6 sptmni (inducie) i
ulterior la 8 sptmni (meninere)
Adalimumab (1fiol = 40 mg) se administreaz subcutanat
160 mg la sptmna 0, 80 mg n sptmna 2 (inducie) i
ulterior 40 mg la 2 sptmni (meninere)

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122

Agenii biologici

_____________________________________

i-au dovedit utilitatea i n manifestrile extraintestinale


(pyoderma gangrenosum, uveit, spondilit)
durata tratamentului de meninere nu este definit (2 ani
dup obinerea remisiunii profunde, cu vindecarea
mucoasei?)
efecte secundare:
- reacii alergice (infliximab)
- risc de reactivare a unor infecii latente (TBC, hepatit
viral etc); este obligatoriu screeningul infeciilor i
vaccinarea nainte de nceperea terapiei biologice
- risc neoplazic: melanom, cancere cutanate nonmelanozice, limfoame (la brbaii tineri risc pentru
limfomul hepato-splenic cu celule T asociat cu
mortalitate crescut)
- formare de autoanticorpi, afectare neurologic (mielit,
nevrit optic), hepatotoxicitate, insuficien cardiac

Abordarea terapeutic n trepte

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_____________________________________
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Step up: se ncepe cu 5 ASA, corticoterapie,


imunmodulator, terapia biologic fiind rezervat cazurilor
refractare sau corticodependente (dezavantaje: efecte
secundare corticoterapie, nu modific evoluia bolii);
Varianta recomandat de protocolul romnesc!
Top down: introducerea terapiei biologice nc de la
nceputul bolii (dezavantaje: riscul efectelor secundare,
costuri, overtreatment)
Step up accelerat: permite introducerea precoce a
terapiei biologice la pacienii cu factori de prognostic
nefavorabil (vrsta tnr, boal extins, fistule, afectare
perianal, ulceraii profunde la endoscopie)

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123

124

CANCERUL
COLORECTAL
_____________________________________
_____________________________________

Epidemiologie

_____________________________________

A 3-a cauz de morbiditate prin cancer


5 6% din populaia globului va dezvolta CCR pe
parcursul vieii

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_____________________________________

A 3-a cauz de deces - F - dup sn, uter

_____________________________________

- B - dup plmn, stomac


Incidena a rmas aceeai, mortalitatea a sczut n ultimii
30 de ani
A crescut localizarea proximal comparativ cu cea
distal
Dup 50 ani riscul crete exponenial (mutaii genetice
succesive acumulate)

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_____________________________________

Epidemiologie

_____________________________________
_____________________________________

Variabilitate geografic foarte mare; inciden:


- crescut > 30/100.000 loc - SUA,Europa de Vest

_____________________________________
_____________________________________

- intermediar - 20-30 /100.000 loc Europa de Est

_____________________________________

- joas 20/100.000 loc - Africa

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_____________________________________

Romnia - 10,1/100.000 sex M

_____________________________________

- 7,3/100.000 sex F

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125

Factori de risc

_____________________________________

I.

Factori genetici
1. ereditari
- polipoza adenomatoas familial (FAP)
- cancerul colorectal ereditar non-polipozic (HNPCC)
2. istoricul personal sau familial de adenoame sau CCR
II. BII
III. Factorii de mediu
IV. Ali factori
Interaciunea dintre factorii genetici i cei de mediu:
- 75% cancere sporadice (factori de mediu)
- 20% predispoziie familial
- 5% sindroamele de polipoz (FAP, HNPCC, Peutz
Jeghers, Cowden)

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Caracteristici n CCR ereditar (FAP sau HNPCC):

_____________________________________

Diagnostic la vrst < 50 de ani


Numr crescut de polipi
Cancere sincrone sau metacrone
Tumori benigne sau maligne extracolonice
Multiple rude, generaii succesive afectate

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Polipoza adenomatoas familial (FAP)


boal autosomal dominant, mutaii gena APC sau gena
MYH (20%)

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_____________________________________
_____________________________________

poate asocia manifestri extracolonice: hipertrofia


epiteliului pigmentar retinian, osteoame, chisturi
epidermoide i sebacee, tumori desmoide (sindrom
Gardner)

_____________________________________

caracterizat prin prezena a mii de polipi adenomatoi


cu transformare neoplazic dac nu sunt extirpai

_____________________________________

vrsta medie de apariie - 16 ani, CCR n jur de 39 ani

_____________________________________

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126

Polipoza adenomatoas familial (FAP)


risc crescut de adenoame i adenocarcinoame: duoden,
jejun, stomac, pancreas, tract biliar + cancer de tiroid,
glioame
se recomand testarea mutaiei APC ( MYH) la toi cei
cu > 100 adenoame colonice i la toate rudele de gradul
I ale pacienilor cu FAP
colectomie profilactic

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_____________________________________

Polipoza adenomatoas familial atenuat: prezena <


100 de adenoame, apare cu 10 ani ntrziere fa de
FAP, polipi localizai cel mai frecvent n colonul proximal

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HNPCC (sindromul Lynch)


Sindrom autosomal dominant, caracterizat prin mutaia
uneia din genele implicate n repararea ADN ului;
molecular - instabilitatea microsateliilor (MSI)
CCR cu debut precoce (45 ani), proximal + cancere
extracolonice
Criterii de diagnostic (Amsterdam):
minim 3 subieci nrudii cu cancer n cadrul sindromului
HNPCC (cancer colorectal, endometru, rinichi, IS,
stomac, pancreas, ovar, tract biliar, creier, cutanat
tumori sebacee)
- dintre care unul s fie rud de gradul I cu ceilali doi
- cel puin 2 generaii succesive afectate
- cel puin un caz s fie diagnosticat sub 50 ani
- absena FAP

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HNPCC (sindromul Lynch)


Screening: testarea MSI (imunohistochimie expresia
proteic a genei MMR)
Criterii de screening (Bethesda):
- CCR diagnosticat la un pacient < 50 de ani
- CCR metacron sau sincron sau tumori extracolonice
asociate indiferent de vrst (asociere de glioame=sindrom
Turcot, keratoacantoame = sindrom Muir-Torre)
- CCR cu instabilitate a microsateliilor nalt identificat
histologic la un pacient < 60 de ani
- CCR sau tumori asociate extracolonice diagnosticate < 50
de ani la cel puin o rud de gradul I
- CCR sau tumori asociate extracolonice diagnosticate la
orice vrst la cel puin dou rude de gradul I sau II
Colectomia profilactic la purttorii mutaiei MMR este
controversat!

127

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Predispoziia familial de CCR

_____________________________________
_____________________________________

Riscul relativ pentru o rud de gradul I afectat este de


1,7

_____________________________________
_____________________________________

Riscul crete n cazul mai multor rude afectate sau n


cazul diagnosticului acestora < 55 ani

_____________________________________
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_____________________________________

Responsabil pentru 20% din CCR

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_____________________________________

BII

_____________________________________

Risc crescut att pentru RCUH ct i pentru BC dup 8 10 ani de evoluie

_____________________________________
_____________________________________
_____________________________________

RCUH colita stng risc de 3 x >, pancolita de 15 x >


comparativ cu populaia general
Asocierea colangitei sclerozante primitive crete riscul
de CCR

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Dup 8 ani supraveghere colonoscopic

_____________________________________
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_____________________________________

_____________________________________

Factorii de mediu

_____________________________________
_____________________________________

Factori de risc:
- obezitatea (mecanisme:sistemul insulin factor de
cretere insuln-like, adipokine, imunomodulare)
- sedentarismul
- consumul excesiv de alcool
- fumatul (rol controversat)
- carnea roie (n special cea prjit), grsimile,
carbohidraii

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128

_____________________________________

Factorii de mediu
Factori protectivi
- Dieta bogat n fructe, legume i fibre alimentare
(antioxidante, antiproliferative, antiinflamatorii, dilueaz
carcinogenii din lumen, inhib activitatea carcinogenetic
bacterian)
- Calciul, vitamina D
- Vitamine A, B, C, E, acidul folic
- Seleniul
Ali factori de risc
DZ
Acromegalia
Colecistectomia
Anastomoza uretero-colic

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Mutaii genetice n adenoame i CCR


Secvena adenom carcinom: 5 10 ani
2 modele:
Modelul
supresor
(instabilitate
cromosomial):
inactivarea genelor supresoare (APC, p53, DCC)
activarea oncogenelor (K - ras)
- aceste mutaii se ntlnesc n 50 -80% din CCR
sporadic
Modelul mutator (instabilitatea microsateliilor - MSI)
mutaii ale genelor reparatorii
n sindromul Lynch dar i n 15 20% din CCR
sporadic (proximal, mai frecvent la femei, slab
difereniat, caracter mucinos)

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Morfopatologie

_____________________________________
_____________________________________

3 5% sincrone sau metacrone


25% - cec i ascendent

_____________________________________

Macroscopic: vegetant, ulcerat, stenozant

_____________________________________

_____________________________________

_____________________________________

Histologic:
- 90 95% adenocarcinoame (variante: carcinomul
mucinos, cu celule n inel cu pecete)
- rar: carcinom cu celule scuamoase, limfom, sarcom,
carcinom nedifereniat

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129

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Stadializarea CCR

_____________________________________
_____________________________________
_____________________________________

Clasificarea Dukes

_____________________________________

Clasificarea TNM

_____________________________________

Invazia tumoral

Afectarea ganglionar

Metastazarea la distan

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Clasificarea DUKES:

_____________________________________
_____________________________________

Stadiul A:

tumora invadeaz mucoasa i submucoasa

_____________________________________

Stadiul B1:

tumora invadeaz musculara proprie

_____________________________________

Stadiul B2:

tumora penetreaz complet musculara proprie i


invadeaz seroasa pn la grsimea pericolic

_____________________________________

orice grad de invazie tumoral cu prinderea <4


ganglioni locoregionali

_____________________________________

Stadiul C2:

orice grad de invazie tumoral cu prinderea >4


ganglioni locoregionali

_____________________________________

Stadiul D:

metastaze n organe la distan

Stadiul C1:

_____________________________________

_____________________________________

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_____________________________________

Clasificarea TNM

_____________________________________

T0=fr evidena tumorii primare


Mo =fr MTS
Tis=carcinom in situ
M1 = MTS prezente
T1=tumor ce invadeaz submucoasa
T2=tumor ce invadeaz muscularis propria
T3=tumor ce invadeaz peretele muscular pn la seroas
T4=tumor ce invadeaz direct alte organe sau structuri i/sau perforeaz
peritoneul visceral

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N0=fr metastaze n ganglionii regionali


N1=metastaze n 1-3 ganglioni pericolici sau perirectali
N2=metastaze n >4 ganglioni pericolici sau perirectali
N3 = metastaze n oricare din ganglionii situai n lungul arterelor ileocolice,colic stng,medie,dreapt, mezenterica inferioar i rectala
superioar

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130

_____________________________________

Stadiul

TMN

Dukes

Supravieuirea
la 5 ani

_____________________________________

>95%

_____________________________________

_____________________________________

Std 0

Tis

No

Mo

Std II

T1/T2

No

Mo

80-95%

_____________________________________

Std IIA

T3

No

Mo

72-75%

_____________________________________

Std IIB

T4

No

Mo

65-66%

_____________________________________

Std IIIA

T1/T2

N1

Mo

55-60%

_____________________________________

Std IIIB

T3/T4

N1

Mo

35-42%

Std IIIC

Oricare T N2

Mo

25-27%

Std IV

Oricare T Oricare N M1

0-7%

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Diagnostic clinic

_____________________________________

Pacieni simptomatici:

_____________________________________

- tulburri de tranzit recent instalate: constipaia colon


stng, diareea colon drept, alternan constipaie - diaree

_____________________________________

- rectoragie: de obicei n neoplasmele stngi

_____________________________________

- anemie feripriv (colon drept)

_____________________________________

- dureri abdominale, simptomatologie suboclusiv

_____________________________________

- defecaie incomplet, tenesme rectale, scaun n creion

_____________________________________

- formaiune palpabil

_____________________________________

- simptome legate de metastaze: ascit, hepatomegalie


dureroas

_____________________________________

Pacieni asimptomatici(screening i supraveghere)

_____________________________________
_____________________________________

Tueu rectal!

_____________________________________
_____________________________________

Explorri paraclinice

_____________________________________
_____________________________________

Teste de laborator: hemoragii oculte, anemie, teste


hepatice (MTS hepatice), ACE rol n supraveghere
Teste genetice identificarea mutaiilor
Colonoscopia cu biopsie standardul de aur
Clisma baritat cu dublu contrast
Colonografia CT (colonoscopia virtual)
Videocapsula colonic
Explorri necesare stadializrii: ecografie abdominal,
Rx torace, ecoendoscopie (apreciaz extensia n
perete), CT cu substan de contrast, tomografie cu
emisie de pozitroni (PET)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

131

Diagnostic diferenial

_____________________________________
_____________________________________

Hemoroizi, fisuri anale


BII
Diverticuloza colonic
Colita ischemic i colita radic
Angiodisplazia colonic
Colonul iritabil
Tuberculoza intestinal
Endometrioza intestinal
Limfomul intestinal
Alte cancere digestive

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Evoluie. Prognostic

_____________________________________
_____________________________________

evoluie lent progresiv

_____________________________________

pacieni cu CCR recidivant - supravieuire < 5 ani de la


diagnostic

pacieni cu metastaze hepatice - supravieuire 4,5 luni

_____________________________________
_____________________________________
_____________________________________

diagnostic precoce i chirurgie n stadiile curabile supravieuire la 5 ani 80%

_____________________________________
_____________________________________
_____________________________________

Complicaii: metastazarea, ocluzia, perforaia,


hemoragia

_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tratament

_____________________________________

Tratament chirurgical
Colectomie, cu excizia tumorii, margine de siguran de
2 5 cm, excizia mezenterului, a grsimii pericolice i a
ganglionilor de drenaj
n FAP colectomie total cu anastomoz ileoanal/rectal
Obstucie, perforaie colostom, cu restabilirea
continuitii dup 4 8 sptmni
Colectomia laparoscopic scurteaz spitalizarea,
necesarul medicaiei postoperatorii nu se practic n
mod curent
Tratamentul MTS hepatice: rezecie, hepatectomie,
alcoolizare, ablaie prin radiofrecven

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

132

Tratament

_____________________________________

Chimioterapia
Adjuvant (dup intervenia chirurgical) n stadiul III,
controversat n stadiul II
Schema standard: 5 fluorouracil asociat cu acid folinic i
oxaliplatin, 6 luni
Capecitabina, Irinotecan linia a II-a
Agenii biologici
- Cetuximab: anticorp monoclonal care blocheaz receptorul
factorului epidermal de cretere asociat cu ligandul su
- Bevacizumab: anticorp monoclonal recombinat umanizat
al factorului de cretere al endoteliului vascular blocheaz
angiogeneza
n cancerul avansat: 5 fluorouracil + acid folinic + irinotecan
sau oxaliplatin + bevacizumab (supravieuire 20 24 luni n
CCR metastatic)

_____________________________________

Tratament

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________

Tratamentul cancerului rectal


Chirurgical: rezecie cu anastomoz colo-rectal,
amputaie de rect cu anus iliac stng
Preoperator: radioterapie asociat cu 5 fluorouracil,
5 zile/sptmn, 6 sptmni
Postoperator: 5 fluorouracil + acid folinic 4 luni

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Profilaxia CCR

_____________________________________

Profilaxia primar
- diet echilibrat, bogat n fructe, legume, fibre,
evitarea crnii roii prjite, combaterea obezitii,
fumatului, consumului excesiv de alcool
- suplimentarea cu calciu, vitamina D, acid folic rol
controversat
- medicamentos:
- aspirina, AINS, inhibitorii COX2
- acidul ursodeoxicolic (colangita sclerozant
asociat BII)
- tratamentul cu derivai 5 ASA n RCUH
- hipolipemiante (simvastatina)

_____________________________________

Screening i supraveghere

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

133

Modaliti de screening n CCR

_____________________________________
_____________________________________
_____________________________________

1. Hemoragii oculte (FOBT)


2 tipuri de teste:
- Guiac au la baz activitatea peroxidaz like a
hemoglobinei fecale (dependente de diet,
medicamente, rezultate fals pozitive i fals
negative)
- Imunochimice recomandate
Avantaje: cost redus, noninvaziv, complian crescut
Dezavantaje: sensibilitate redus (multe adenoame i
cancere nu sngereaz!)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Modaliti de screening n CCR


2. Sigmoidoscopia
Avantaje: pregtire cu clisme, nu necesit sedare, mai
puin invaziv comparativ cu colonoscopia
Dezavantaje: deceleaz numai leziunile distale

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

3. Combinaia FOBT anual + sigmoidoscopie la 5 ani

_____________________________________
_____________________________________

4. Clisma baritat cu dublu contrast nu se mai


folosete ca metod de screening

_____________________________________
_____________________________________
_____________________________________

5. Colonoscopia gold standard


Sensibilitate de 90-95%
Dezavantaje: complian, pregtire, costuri

_____________________________________
_____________________________________

Modaliti de screening n CCR

_____________________________________
_____________________________________
_____________________________________

6. Noi metode de screening (necesit validare n practica


curent)
- Colonoscopia virtual sensibilitate de 81 94%
- Testarea ADN ului fecal: limitat datorit costurilor mari
- Creterea performanei colonoscopiei cromoscopie,
magnificaie, narrow band imaging
- Videocapsula colonic
- Viitor: colonoscopia asistat, colonoscop autopropulsat,
autonavigabil (Aer O Scope)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

134

Recomandri de screening i
supraveghere

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Risc mediu (populaie asimptomatic > 50 de ani)


- Hemoragii oculte anual
- Sigmoidoscopie sau clism baritat cu dublu contrast
sau colonoscopie virtual la 5 ani
- colonoscopie la 10 ani

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Recomandri de screening i supraveghere

_____________________________________

Risc crescut (1)

_____________________________________
_____________________________________

Categorie de
risc
1-2 adenoame < 1 cm
Istoric
personal
de polip
3 10 polipi sau polip >
1 cm sau polip vilos sau
displazie nalt
> 10 polipi

Metod
Colonoscopie la 5
10 ani
Colonoscopie la 3
ani

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Colonoscopie la < 3
ani

Polip sesil (polipectomie Colonoscopie la 3


piecemeal)
6 luni

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Recomandri de screening i supraveghere

_____________________________________
_____________________________________

Risc crescut (2)

_____________________________________
_____________________________________

Istoric
personal de
CCR

perioperator

postoperator

Colonoscopie
nainte de operaie
sau n primele 6 luni
dup

_____________________________________

Colonoscopie la 1,
3, 5 ani de la
explorarea
anterioar

_____________________________________

_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

135

Recomandri de screening i supraveghere

_____________________________________
_____________________________________

Risc crescut (3)


Istoric
familial de
polipi sau
CCR

1 rud grd I < 60 ani sau


2 rude de grd I cu CCR

1 rud grd I > 60 de ani


sau 2 rude grd 2 cu
CCR

_____________________________________

Colonoscopie la 5
ani ncepnd de la
40 de ani sau cu 10
ani mai devreme
dect vrsta
diagnosticului rudei
cu CCR
Orice metod de la
risc mediu la 5 ani

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Recomandri de screening i
supraveghere

_____________________________________
_____________________________________
_____________________________________

Risc nalt
- FAP sigmoidoscopie anual ncepnd de la vrsta de
10- 12 ani

_____________________________________
_____________________________________
_____________________________________

- HNPCC colonoscopie:
- anual sau la 2 ani ncepnd de la vrsta de 20 25
ani sau cu 10 ani mai devreme dect cel mai tnr
membru al familiei diagnosticat

_____________________________________
_____________________________________
_____________________________________
_____________________________________

- BII colonoscopie cu biopsii multiple anual sau la 2 ani


(dup 8 ani)

_____________________________________
_____________________________________
_____________________________________

136

HEPATITA CRONIC
VIRAL C
_____________________________________
_____________________________________

Date generale

_____________________________________

Virusul C- familia flaviviridae, 55-65 nm


6 genotipuri i peste 100 subtipuri
Timp de njumtire ~2,7 ore
Producia zilnic: 10 trilioane de virioni
Infecia cu virus C este responsabil de ~40% din
patologia hepatic
180 milioane persoane, ~3% din populaia globului infectat cronic cu virus C
Prevalena n Romnia 4,9% predomin genotipul 1b
(99%)
Hepatita cronic C- cea mai frecvent indicaie de
transplant

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Factori de risc pentru transmiterea VHC


Droguri intravenoase
Antecedente de folosire a altor droguri (cocain,
marijuana)
Activitate sexual cu risc crescut (parteneri sexuali
multipli, vrsta tnr de ncepere a vieii sexuale)
Transfuzii de snge i derivate de snge (n particular
nainte de 1992)
Transplant de organe
Hemodializa
Asistente, doctori - contaminare ace, seringi
Expunere perinatal sub 5%
Stomatologie
Manichiur, pedichiur, piercing, tatuaje
Gradul de srcie, nivelul de educaie
Statusul marital: divorai sau separai

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

137

_____________________________________

Istoria natural

_____________________________________

Infecia acut se rezolv spontan n 20 % din cazuri i se


cronicizeaz n 80 %

_____________________________________
_____________________________________
_____________________________________

Evoluia cronic a infeciei poate fi stabil ( 80%) sau


progresiv spre ciroz ( 20%)
Ciroza hepatic, la rndul ei, poate progresa lent (75%)
sau rapid (25%) spre insuficien hepatic, HCC, deces
n absena transplantului, sub influena factorilor
precipitani (virus B, HIV, alcool, factori genetici etc)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Istoria natural

_____________________________________

Stadiul fibrozei - cel mai important factor prognostic al


evoluiei infeciei cronice

_____________________________________
_____________________________________
_____________________________________

Progresia fibrozei - direct proporional cu: vrsta naintat la


care a survenit infecia (>40 ani), sexul masculin, consumul
exagerat de alcool, coinfecia VHB sau HIV sau transaminaze
crescute persistent

_____________________________________
_____________________________________
_____________________________________

n prezent nu sunt teste serologice standardizate pentru


predicia progresiei fibrozei (colagen tip 4, laminina)
Teste genetice - (gene care determin progresia fibrozei) - nu
se fac uzual

ncrctura viral i genotipul nu par s influeneze semnificativ


progresia fibrozei

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Evaluarea pacientului

_____________________________________

Tablou clinic
Umoral biochimic nu sunt elemente caracteristice; de
obicei prezena sindromului de citoliz oblig
investigarea etiologiei!
Markerii serologici
Evaluarea fibrozei hepatice
Metode imagistice: ecografie, EDS la cei cu fibroz
avansat pentru diagnosticul CH i complicaiilor
acesteia

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
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138

Tablou clinic

_____________________________________

Majoritatea pacienilor sunt asimptomatici


Pot apare simptome nespecifice (cel mai frecvent astenie
neexplicat, dureri musculare, greuri, vrsturi etc.) - nu se
coreleaz cu activitatea bolii
Manifestri extrahepatice:
- crioglobulinemie 40-90%
- afeciuni reumatologice 19-31%
- porfiria cutanea tarda 1-2%
- limfom malign non-Hodgkin 0-42%
- glomerulonefrit 5-10%
- afeciuni autoimune 14-20%
- lichen plan 1-2%
- afeciuni neurologice 5-9%-polineuropatie senzitiv
- afeciuni oculare <1%- retinopatie

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Markerii VHC

_____________________________________

1. Genotipul VHC: 6 genotipuri (1-6), aproximativ 100 subtipuri


- genotipurile 1,2,3 - n ntreaga lume (Romnia 1b 99%)
- genotipurile 4,5 Africa, 6 Asia
- genotipul- caracteristic intrinsec, nu se modific n timp

_____________________________________
_____________________________________
_____________________________________
_____________________________________

2. ARN-VHC
- cel mai bun marker al replicrii virale
- detectabil n sngele periferic la 1-2 sptmni dup
infecie
- difereniaz hepatita acut viral C vindecat de infecia
cronic cu VHC
3. Ac anti-VHC:
- pot fi detectai prin teste uzuale la 7-8 sptmni dup
infecie
- n infecia cronic persist toat viaa

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Evaluarea practic a fibrozei hepatice

_____________________________________
_____________________________________

3 modaliti:

_____________________________________

Teste non-invazive sanguine care evalueaz singure sau


combinate fibroza hepatic (Fibrotest, FibroMax)

_____________________________________

Metode imagistice (elastometrie Fibroscan)

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Puncia biopsie hepatic

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

139

_____________________________________

Tratament

_____________________________________

Scopuri principale:

_____________________________________

Eradicarea viral cu obinerea rspunsului viral


susinut (RVS)
RVS este echivalent cu vindecarea viral(cure
hepatitis)

_____________________________________
_____________________________________
_____________________________________

Scopuri secundare:

_____________________________________

ncetinirea progresiei fibrozei


prevenirea apariiei hepatocarcinomului
prelungirea supravieuirii
mbuntirea calitii vieii

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Ideal orice pacient cu hepatit cronic cu virus C


beneficiaz de tratament antiviral

_____________________________________
_____________________________________

Schema de tratament actual n Romnia

_____________________________________
_____________________________________
_____________________________________

INTERFERON PEGYLAT subcutanat


- 180g/sptmn PEG alfa 2a sau
- 1,5 g/kgc/ sptmn PEG alfa 2b

_____________________________________
_____________________________________

_____________________________________

RIBAVIRIN 13,5 mg/kgc (per os, tableta de 200 mg, 800


1200 mg/zi)

_____________________________________
_____________________________________

RVS 50%

_____________________________________

! Durata tratamentului se face n funcie de valoarea


iniial a viremiei, stadiul fibrozei i tipul de rspuns viral
la tratament (clasic 48 sptmni)

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Contraindicaiile absolute ale tratamentului


antiviral

_____________________________________
_____________________________________
_____________________________________

Interferon: afeciuni psihiatrice cu component major


depresiv, ciroza decompensat, boli autoimune,
afeciuni cardiace severe

Ribavirin:anemie preexistent (<10g/dl), insuficien


renal, cardiopatie ischemic
Atenie: perioda fertil (risc teratogen), nu se administreaz
n alptare

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

140

Tipuri de rspuns n raport cu nivelul ARN-VHC


n terapia cu IFN pegylat + RBV

_____________________________________

Rspuns virusologic rapid (RVR) complet - ARN-VHC


nedetectabil la sptmna 4

_____________________________________

Rspuns virusologic precoce (RVP) complet - ARNVHC nedetectabil la sptmna 12

_____________________________________

Rspuns virusologic precoce parial - scderea cu 2


log a ARN-VHC la 12 sptmni, ARN-VHC nedetectabil
la 24 sptmni

_____________________________________

_____________________________________

_____________________________________

_____________________________________

_____________________________________
_____________________________________

Rspuns virusologic la sfritul tratamentului - viremie


nedetectabil la sfritul tratamentului (24 sau 48 de
sptmni)
Rspuns virusologic susinut - ARN VHC nedetectabil
la 24 sptmni de la terminarea tratamentului

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Non-responder:
a. rspuns virusologic nul: lipsa scderii cu 2 log a
ARN - VHC la 12 sptmni
b. rspuns virusologic parial: scderea cu 2 log la 12
sptmni, dar ARN - VHC rmne detectabil

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Breakthrough- ARN - VHC nedetectabil precoce,


detectabil oricnd nainte de ncheierea tratamentului

_____________________________________
_____________________________________

Recdere ARN - VHC nedetectabil la sfritul


tratamentului, detectabil la monitorizarea posttratament

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Factori de prognostic ai rspunsului la tratament


Genotipul viral 2,3 - cea mai mare rat de rspuns
Gradul de fibroz cu ct fibroza >, RVS <
ncrctura viral invers proporional
Rasa afroamericani - rspuns sczut la tratament
datorit predispoziiei genetice de a activa IFN endogen,
la asiatici - rspuns mai bun
Nivelul ALT- rspuns invers proporional
Greutatea corporal invers proporional (obezitatea
contribuie la progresia rapid a fibrozei)
Consumul de alcool progresie rapid a fibrozei, HCC
Sexul, vrsta i momentul infeciei F<40 ani, infecie
recent- rspuns favorabil
Coinfecie HIV+ VHC scade RVS
Esenial: evitarea ntreruperii i pstrarea ribavirinei >60%
doz cumulativ!

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

141

_____________________________________

Markeri genetici n evaluarea rspunsului la


tratamentul cu IFN pegylat + RBV

_____________________________________
_____________________________________

Polimorfismul interleukinei 28B (lambda 3 interferon de pe


cromosomul 19)

_____________________________________
_____________________________________

IL28B (poziia alelelor citozin-timidin)


CCRVS 69%
crete compliana i motivez pacientul
CT RVS 33% nnu este recomandat de rutin
TT RVS 27%

_____________________________________

Nu se cunoate rolul IL 28B n tripla terapie sau regimurile


interferon free

_____________________________________

_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________

Efecte adverse obinuite la dubla terapie


De obiecei sunt uoare sau moderate
Au gravitate medie <10% din pacieni - necesit
monitorizare
Severe i ireversibile sunt extrem de rare
Reacii la locul injeciei, dermatite, alopecie
Sindrom pseudogripal (cefalee, febr, astenie, mialgii,
inapeten); cel mai frecvent bine controlat cu
paracetamol
Afectare hematologic: leucopenie, trombopenie - IFN;
anemie hemolitic - RBV
Tulburri psihice (depresie, iritabilitate, insomnii)
Accentuez disfuncii tiroidiene preexistente

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

2011

_____________________________________

Au fost aprobate n SUA i apoi n Europa 2 medicamente cu


aciune antiviral direct (DAA)
Acestea sunt inhibitori de proteaz N3/N4- Boceprevir i
Telaprevir
Asocierea DAA la biterapie a determinat creterea RVS n
genotipul 1a,b
IFN pegylat + RBV + antivirale cu aciune direct (DAA)
(boceprevir, telaprevir)
RVS crete cu 21 - 31% - naivi
40 - 60% - recdere
33 - 45% - parial responderi
24 - 28% - non-responderi

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

142

_____________________________________

Efecte secundare la tripla terapie


Efectele secundare sunt aditive i cumulative cu cele ale
dublei terapii
Sunt reversibile dup ntreruperea tratamentului
Efecte noi: Boceprevir- ageuzie
Telaprevir- manifestri anorectale i exantem
cu diferite grade

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Atenie: diminuarea dozelor de DAA determin rezistense impune NTRERUPEREA TRATAMENTULUI, NU


SCDEREA DOZELOR DE ANTIVIRALE CU ACIUNE
DIRECT!

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Viitor

_____________________________________
_____________________________________

Regimuri interferon free


Antivirale orale singure sau combinate ribavirin
Scurtarea terapiei
Creterea RVS>90%
Substana ideal- tableta unic, aciune pe toate
genotipurile, efecte secundare neglijabile, administrare
indiferent de vrst, comorbiditi sau asocieri virale, costuri
mici

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

143

144

HEPATITA CRONIC
VIRAL B
_____________________________________
_____________________________________

Epidemiologie

_____________________________________

Peste 350 milioane persoane purttoare de Ag HBs pe


glob

_____________________________________
_____________________________________
_____________________________________

Prevalen:
- sczut (<2%): Europa de Vest, SUA, Canada, Australia, Noua

_____________________________________

Zeeland

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- medie (2-7%): ri mediteraneene, Japonia, Asia Central, Orientul

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Mijlociu, America Latin; Romnia 6%

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- ridicat (> 8%): Asia de Sud, China, Africa

_____________________________________

Spectrul bolii: purttor cronic inactiv hepatit cronic


ciroz hepatic - hepatocarcinom

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Virusul hepatic B

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x VHB face parte din familia hepadnaviridae


Genomul viral este un ADN dublu catenar, circular, deschis;
proteinele majore virale sunt codate de 4 gene
Virusul are opt genotipuri (A-H), a cror prevalen variaz n
funcie de zona geografic

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Mod de transmitere:
- vertical (mame Ag HBs +)
- orizontal (n special n ariile endemice)

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145

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Factori de risc pentru transmiterea VHB:


- transmiterea vertical
-activitatea sexual cu risc crescut (parteneri
sexuali multipli, homosexualitate)
-droguri intravenoase
-hemodializa
-ariile de nalt endemicitate
-profesia medical
-stomatologie
-manichiura, tatuaje, piercing

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Tablou clinic

_____________________________________

Pacienii sunt n general asimptomatici

_____________________________________

Simptomatologia hepatitei cronice este nespecific :


astenie, dureri n hipocondrul drept, scderea apetitului,
grea, subicter

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_____________________________________

Manifestrile extrahepatice (20%) includ:


-artralgii (cea mai frecvent manifestare
extrahepatic)
-glomerulonefrit
-periarterit nodoas
-criglobulinemie mixt esenial

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Teste serologice
Diagnosticul infeciei VHB se bazeaz n general pe
detectarea AgHBs, primul marker viral detectabil n ser
Anticorpii anti-HBc din clasa IgM apar n primele 6 luni de la
infecia acut (pot apare ocazional i n cursul episoadelor de
reactivare a infeciei cronice)
IgG anti HBc apar dup 6 luni, fiind un indicator al infeciei
cronice
Ag HBe/Ac HBe definesc tipul de hepatit cronic (Ag Hbe
pozitiv sau negativ)
Replicarea viral activ este definit de prezena AgHBe
i/sau a ADN VHB
Ac anti HBs reprezint anticorpi protectori, markeri ai
vindecrii i ai imunitii la reinfecie. Pot fi indui de
vaccinarea VHB

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146

Istoria natural

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_____________________________________

Hepatita viral B este o boal heterogen care se poate vindeca


spontan sau poate evolua ctre diferite forme de infecie
cronic
Riscul cronicizrii:
- 90% din copiii infectai n primul an de via
- 30 50% din copiii infectai ntre 1 i 4 ani
- 5% din adulii sntoi
- 50% din adulii imuncompromii
Seroconversia spontan (pierderea Ag HBs): 0,5 1%/an
Infecia cronic viral B:
- 10 20% n 5 ani CH 15% n 5 ani HCC
15% n 5 ani decompensare hepatic
15% n 5 ani deces
- 5 10% HCC

Fazele infeciei cu VHB


Faza de toleran imun: pacientul este AgHBe
pozitiv, cu un nivel crescut al ADN VHB , transaminaze
normale i histologie hepatic normal.
Faza de activitate imun: nivel fluctuant al ADN VHB
(scade progresiv); transaminaze i activitate histologic
crescute.
Faza non replicativ sau de purttor inactiv:
seroconversia AgHBe cu apariia Ac anti HBe; scdere
important a ADN VHB n snge, transaminaze normale,
scderea activitii necroinflamatorii hepatice.
Reactivarea replicrii virale: creterea ADN VHB,
recrudescena bolii hepatice, spontan sau dup ntreruperea
tratamentului antiviral.
Clearance-ul AgHBs: dispariia AgHBs, apariia Ac anti
HBs; ADN VHB poate rmne n continuare detectabil prin
PCR n ser sau n specimenele de biopsie hepatic

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Semnificaia titrului Ag HBs


Reflect activitatea transcripional a cccADN
Titrul este > la pacienii Ag Hbe pozitiv, comparativ cu cei
Ag Hbe negativ
Se coreleaz invers cu fibroza hepatic la pacienii Ag Hbe
pozitiv
Titrul < 1000 UI/ml asociat cu ADN VHB < 2000 UI/ml
difereniaz hepatita cronic Ag Hbe negativ de purttorii
cronici inactivi
Rol n monitorizarea tratamentului cu interferon (lipsa
scderii titrului Ag HBs sau a scderii viremiei cu 2 log la
sptmna 12 au rol predictiv pentru lipsa RVS ntreruperea tratamentului!)
Rolul n monitorizarea tratamentului cu analogi nucleozidici
nu este clarificat

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147

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Complicaii i mortalitate

_____________________________________

Carcinomul hepatocelular
- >10 ori n infecia B fa de populaia general
- risc inclusiv la purttorii cronici inactivi sau la cei cu
clearance Ag HBs!!
Ciroza hepatic

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_____________________________________
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Mortalitatea (5 ani):
n hepatita cronic B 0-1 %;
n ciroza hepatic viral B compensat 14-20%;
n ciroza decompensat 65-85%.

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_____________________________________

Prognostic - negativ
Factori legai de virus:
replicarea activ a VHB (no virus, no disease!)
genotipul viral
coinfecia cu VHC, VHD sau HIV
Factori legai de gazd
vrsta diagnosticrii (istoric lung de boal)
sexul masculin
episoadele recurente de reactivare a hepatitei
severitatea bolii hepatice n momentul diagnosticrii
Factori externi
alcoolul
fumatul
carcinogenii din diet (aflatoxinele)

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Evaluarea iniial

_____________________________________

Anamneza i examenul clinic: factorii de risc ai transmiterii


VHB, antecedentele familiale de infecie viral B sau cancer
hepatic indus de VHB, consumul de alcool

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Diagnosticarea unor posibile coinfecii: VHD, VHC, HIV (la


cei cu risc)

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_____________________________________

Vaccinarea pentru hepatita A n ariile cu prevalen crescut


- la toi pacienii cu infecie cronic VHB i cu anticorpi anti
hepatit A abseni

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Testarea rudelor de gradul I n zonele cu transmitere


vertical sau orizontal n cursul copilriei timpurii

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148

Testarea pacienilor naintea includerii n


tratament
ALT, AST (nivelele pot fi fluctuante: se recomand
repetare la 3 6 luni n cazul valorilor normale)
Titrul Ag HBs
Ag HBe, Ac anti-HBe
Ac anti VHD, Ac anti VHC
ADN VHB
Evaluarea afectrii hepatice: invaziv (PBH) sau noninvaziv (FibroMax)
Hemogram, funcia hepatic
Ecografie, EDS (criterii de HTP)

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Obiectivele tratamentului

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Infecia viral B nu poate fi complet vindecat (cccADN)!


Supresia susinut a replicrii virale:
- ameliorarea procesului hepatitic (normalizarea ALT)
- ameliorarea sau reversibilitatea procesului inflamator
hepatic i a fibrozei
- ameliorarea prognosticului pe termen lung (prevenire CH,
HCC)

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Indicaii terapeutice (1 3)
1. Hepatita cronic viral B n faza de activitate imun i
reactivare a replicrii virale (NU se trateaz pacienii
aflai n toleran imun sau purttorii cronici inactivi
conform ghidurilor actuale)
- Ag HBe +: ADN VHB > 20 000 UI/ml (100 000
copii/ml) i
ALT 2xN sau ALT < 2 x N i evidena
prezenei activitii necro-inflamatorii i fibrozei (PBH sau
FibroMax)
- Ag HBe - : ADN VHB > 2000 UI/ml (10 000 copii/ml)
i
ALT 2xN sau ALT < 2 x N i evidena
prezenei activitii necro-inflamatorii i fibrozei (PBH sau
FibroMax)

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149

Indicaii terapeutice

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2. Ciroza hepatic viral B


- compensat: ADN VHB 2000 UI/ml indiferent de
statusul HBe
- decompensat: ADN VHB pozitiv, indiferent de
valoare

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3. Pacieni imunosupresai Ag HBs +

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Opiuni terapeutice actuale


n Romnia

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INTERFERON PEGYLAT

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ANALOGI NUCLEOZ(T)IDICI (AN) (Lamivudin,


Entecavir, Adefovir, Tenofovir)

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Interferon vs analogi

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Interferon
- Avantaje: durat finit a tratamentului, seroconversie >
Ag HBe, Ag HBs (efectul continu i dup ntreruperea
tratamentului), lipsa rezistenei
- Dezavantaje: administrare subcutanat, efecte
secundare multiple
Analogi
- Avantaje: efect antiviral puternic, administrare per os,
efecte secundare minime, se pot administra i n ciroza
hepatic decompensat
- Dezavantaje: durat nedefinit a tratamentului (toat
viaa?), apariia rezistenei ce poate limita terapiile
ulterioare

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150

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Interferonul pegylat -2a

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_____________________________________

Peginterferon alfa 2a, 48 sptmni

_____________________________________

Se prefer la pacienii tineri, imunocompeteni, fr


ciroz sau contraindicaii la interferon i la cei cu viremie
redus (<107 UI/ml)

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Suprim replicarea viral, stimuleaz rspunsul imun

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Nu induce rezisten

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Contraindicaii, efecte secundare la fel ca n


tratamentul VHC (depresia mai rar!)

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Cnd iniiem tratamentul cu AN?


Hepatita cronic viral B Ag Hbe pozitiv sau negativ
(ADN-VHB, transaminaze, histologie) opiune medic +
pacient; se prefer atunci cnd viremia este > 107 UI/ml
CH viral B
- compensat, AND VHB > 2000 UI/ml, indiferent de ALT
(atenie la ntrerupere risc de exacerbare sau
recdere)
- decompensat tratament coordonat de centrele de
transplant, pe toata durata vieii
Chimioterapie sau imunsupresie
Sarcina
Eec terapie anterioar interferon

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Ce AN alegem?

_____________________________________

Se recomand nceperea terapiei cu analogi cu barier


genetic nalt i poten antiviral mare:
Entecavir 0,5 mg/zi
Tenofovir
Durata tratamentului:
- Ag Hbe poz 6 luni dup seroconversia n e
- Ag Hbe neg seroconversia n s, viremie nedetectabil
Obiective greu de obinut n practic; protocol Romnia
maxim 5 ani; durat indefinit?

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151

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Efecte secundare AN

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Rezistena viral
- ridicat la lamivudin (65-70% la 5 ani!)
- intermediar la telbivudin i adefovir
- joas pentru entecavir i tenofovir

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n cazul apariiei rezistenei se prefer


Strategii add-on cu clase diferite
Preferabil vs. switch

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AN au eliminare renal; se recomand ajustarea dozelor


n caz de clearance de creatinin sczut

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Profilul de siguran pe termen lung sau n cazul


asocierilor de AN nu este pe deplin cunoscut!

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Lamivudina

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_____________________________________

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Analog nucleozidic ce inhib ADN polimeraza viral


100 mg/zi
Avantajul terapiei cu lamivudin este profilul de
siguran i costul relativ sczut
Principalul dezavantaj este apariia rezistenei virale
datorate mutaiilor YMDD n regiunea C a genei
polimerazei VHB
Apariia virusului mutant duce la reactivarea hepatitei
cronice, avnd un efect negativ asupra biochimiei i
histologiei hepatice
Nu se folosete ca tratament de prim intenie la naivi
Da: sarcin, pacieni n tratament cu imunsupresoare

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Entecavir

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Induce rapid supresia viral


0,5 mg/zi la naivi, 1 mg/zi la cei pretratai cu lamivudin
Ajustarea dozelor n insuficiena renal
Acidoz lactic la cei cu CH
Barier genetic , rezisten
Cel mai utilizat AN n prezent, att la naivi ct i la
pretratai

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Adefovir (10 mg/zi), tenofovir (300 mg/zi) n special n


caz de rezisten sau non-rspuns primar la entecavir
(add on, switch); tenofovirul femei nsrcinate

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152

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Transplantul hepatic

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Singura opiune la pacienii cu boal hepatic n stadii


terminale

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Pentru
prevenirea
recurenei
infeciei
VHB
posttransplant se administreaz pre i perioperator
imunoglobuline specifice B (HBIG), asociat cu AN cu
barier crescut la rezisten, pre i post - transplant

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Viitor?

_____________________________________

Ali ageni terapeutici


- Telbivudina inhib replicarea viral, rezisten ,
miopatii, neuropatii rol limitat
- Emtricitabin, Clevudine, Thymosin
- noi ageni care s intervin n alte faze ale ciclului
replicrii virale sau s restaureze rspunsul imun
Combinaii pn n prezent nici o asociere IFN/AN sau
mai muli AN nu i-a dovedit superioritatea
Selecia adecvat a pacienilor (polimorfismul IL28B rol
controversat n hepatita cronic VHB), individualizarea
terapiei
Vaccinare, prevenie eradicare infectiei dispariia
virusului B?

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HEPATITA CRONIC
B +D

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VHD virus satelit, dependent de VHB pentru producerea


proteinelor de nveli

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Coinfecie sau suprainfecie VHD


- Coinfecie B plus D: risc > de hepatit acut fulminant,
cronicizare rar
- Suprainfecie D (hepatit acut la un purttor VHB
asimptomatic sau exacerbarea unei hepatite cronice VHB)
cronicizare 70 90%
accelerarea evoluiei spre CH, decompensare,
HCC

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153

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Markerii infeciei active VHD

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Ig M anti VHD (diferenierea ntre


suprainfecie/coinfecie se face prin absena/prezena
IgM anti HBc)

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ARN VHD

_____________________________________

Ag HVD prin imunohistochimie la nivelul esutului


hepatic

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Tratament
La pacienii Ag Hbs pozitiv, Ac HVD pozitiv - criterii de
includere: ALT> 2xN, sau ALT< 2xN cu activitate necroinflamatorie 4 sau fibroz 1 (PBH, FibroMax)
Se determin ARN-VHD:
- pozitiv tratament
- negativ se determin ADN VHB:
> 2000 UI/ml se trateaz la fel ca VHB
< 2000 UI/ml - monitorizare

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Peginterferon 2a sau b,1 an; RVS 25 40%


AN nu au eficacitate
Transplant hepatic

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154

FICATUL GRAS
NONALCOOLIC
_____________________________________
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Definiie. Termeni

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Acumularea hepatocelular de trigliceride n absena


consumului semnificativ de alcool

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Ficatul gras non-alcoolic (nonalcoholic fatty liver disease


- NAFLD) include:
- steatoza
- steatohepatita (nonalcoholic steatohepatitis NASH)

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Poate evolua spre ciroz hepatic i hepatocarcinom

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Epidemiologie

_____________________________________

Cea mai frecvent afeciune hepatic

_____________________________________

Prevalen: 10 24% din populaia general

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_____________________________________

Prevalen n cretere la copii: 20 50% din copiii obezi


(inclusiv n Romnia)
Inciden n cretere n rile dezvoltate, paralel cu
creterea obezitii, DZ

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Responsabil de 70% din cirozele criptogenetice

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B>F, albi>negri

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155

Etiologie
Primar expresia hepatic a sindromului metabolic
(3 din: circumferinei taliei, hipertrigliceridemie, HTA,
glicemiei, HDL colesterolului)
- obezitatea: 40 100%
- hiperglicemia: 25 75%
- hiperlipemia: 20 80%
Secundar:
- medicamente: glucocorticoizi, estrogeni, tamoxifen,
amiodaron
- nutriional: malnutriie, Kwashiorkor, deficien de
colin, by-pas jejuno-ileal, gastroplastie, rezecii de
intestin subire, nutriie parenteral total
- afeciuni hepatice: Wilson, hepatita cronic VHC,
glicogenoze

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Fiziopatologie
First hit insulinorezistena stimuleaz sinteza de
trigliceride i acumularea de acizi grai liberi n ficat
Second hit stress oxidativ - peroxidarea lipidelor
eliberarea de radicali liberi de oxigen atragerea
mediatorilor inflamatori (TNF, citokine inflamatorii)
injurie hepatic
Leptina (hormon citokin like, produs de adipocite i de
celulele stelate hepatice) - n sindromul metabolic rol
n progresia NASH
Adiponectina hormon secretat de grsimea omentalstimuleaz utilizarea glucozei i oxidarea acizilor grai;
se coreleaz invers cu sindromul metabolic, insulinorezistena i NASH

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Clasificarea morfologic
(Matteoni)

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1. Steatoz simpl (absena inflamaiei i fibrozei)

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2. Steatoz cu prezena inflamaiei lobulare dar cu


absena fibrozei sau a celulelor balonizate

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_____________________________________

3. Steatoz + inflamaie + degenerare balonizat

_____________________________________

4. Steatoz + inflamaie + fibroz (caracteristic


perivenular i perisinusoidal) + celule balonizate +
corpi hialini Mallory

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156

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Diagnostic clinic

_____________________________________
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Nu exist manifestri clinice specifice!

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Majoritatea pacienilor sunt asimptomatici

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Astenie, jen dureroas n hipocondrul drept

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Hepatomegalie 75% din cazuri

_____________________________________

n evoluie semne de hepatit cronic sau ciroz


hepatic

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Diagnostic paraclinic

_____________________________________
_____________________________________

Umoral biochimic

_____________________________________

- ALT i AST; AST/ALT <1 (difereniere de hepatita


alcoolic); raportul se poate modifica odat cu progresia
fibrozei
- fosfataza alcalin, bilirubina de obicei normale
- feritina 50% din NASH
- sunt crescute: glicemia, trigliceridele, colesterolul,
acidul uric
- insulino-rezisten (se determin prin metoda HOMA)

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Diagnostic paraclinic
Imagistic
- ecografia abdominala steatoz difuz sau focal
- computer tomografia (fr substan de contrast)
- rezonana magnetica metoda cea mai sensibil dar
cea mai scump!
Limite: nu difereniaz steatoza de steatohepatit, nu
cuantific inflamaia i fibroza!

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PBH imperfect gold standard

_____________________________________

- confirm diagnosticul, stabilete severitatea afectrii


hepatice, evideniaz extinderea fibrozei
- controversat att timp ct nu influeneaz terapia

_____________________________________

Metode non-invazive:

fibroscan, fibromax,
steatotest etc nu au intrat n practica curent

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157

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Diagnostic pozitiv

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_____________________________________

istoric negativ pentru consumul de alcool

_____________________________________

markeri virali negativi

_____________________________________

obezitate, DZ, hiperlipemie

_____________________________________

hepatomegalie

_____________________________________

cretere moderat ALT, AST

_____________________________________

fosfataza alcalin normal

_____________________________________

creteri moderate pentru GGTP

_____________________________________

echografic steatoz hepatic o ciroz

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_____________________________________
_____________________________________

_____________________________________

Diagnostic diferenial

_____________________________________
_____________________________________

Hepatita alcoolic
Hepatite virale
Hepatita autoimun
Hepatite medicamentoase
Hemocromatoz
Afeciuni tiroidiene
Boal Wilson
Deficitul de alfa 1 antitripsin

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Evoluie. Complicaii.
Prognostic

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Steatoza hepatic nu progreseaz spre ciroz


hepatic, dar crete riscul cardiovascular
20% din pacienii cu NASH progreseaz spre ciroz
hepatic
Factori de prognostic negativ: obezitatea, DZ, HTA,
vrsta naintat
Mortalitate: 11% la 10 ani pentru pacienii cu fibroz
10% din indicaiile de transplant hepatic sunt consecina
cirozei hepatice induse de NASH
Risc de hepatocarcinom!!!

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158

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Tratament

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1. Scderea n greutate

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Msuri igieno dietetice (diet, exerciiu fizic)


Terapie medicamentoas: orlistat, sibutramin
Chirurgie bariatric (indicat la IMC > 40)

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2. Scderea rezistenei la insulin

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Metformin rezultate promitoare experimental, pn


n prezent nu i-a dovedit eficiena la om
Tiazolidindione: rosiglitazona, pioglitazona
- cresc sensibilitatea la insulin prin creterea produciei
de adiponectin
- amelioreaz probele hepatice i histologia
- efecte secundare: creterea n greutate

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Tratament

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3. Combaterea stressului oxidativ

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Acidul ursodeoxicolic (efect citoprotectiv,


imunomodulator, anti apoptotic) eficacitate limitat pe
termen lung comparativ cu placebo
Vitamina E rezultate favorabile, mbuntirea scorului
de steatoz i inflamaie
Betaina, N acetyl-cysteina necesit confirmare
Pentoxifilin inhib TNF rezultate ncurajatoare pe
modele animale
Probioticele (lipopolizaharidele bacteriene sunt
hepatotoxice i cresc mediatorii pro-inflamatori) studii
limitate

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Tratament

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4. Hipolipemiante

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Fibrai, statine rol limitat n NASH dar scad riscul


cardiovascular
Statinele (efecte secundare: toxicitate hepatic i
muscular) s-au dovedit sigure la pacienii cu NAFLD

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5. Transplant hepatic

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159

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Tratament NASH - concluzii

Nici un medicament nu i-a dovedit clar eficacitatea!


Scdere n greutate, exerciiu fizic
NASH + Dislipidemie statine
NASH + DZ tiazolidindione sau metformin
Vitamina E

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160

BOALA HEPATIC
ALCOOLIC
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Definiie: spectru variat de afeciuni (steatoz hepatic

ciroz complicat) cu etiologie comun consumul


cronic de alcool
afectarea hepatic indus de alcool este plurifactorial
butorii cronici dup 10 ani :
90% - steatoz hepatic alcoolic
10 -35% - steatohepatit
8 20% - ciroz

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Factori de risc

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Sexul i vrsta

Femeile - de 2 ori mai expuse comparativ cu barbaii;


explicaii :
concentraii reduse de alcooldehidrogenaz,
obezitate mai frecvent, absorbie modificat n timpul
ciclului menstrual
Consumul de alcool la vrste tinere (< 21 ani), cronic,
indiferent de tipul de alcool consumat, crete riscul de
hepatit alcoolic, fibroz hepatic i ciroz

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Asocierea consumului de alcool cu infeciile virale B,C


Consumul de alcool favorizeaz fibroza i apariia cirozei
n hepatitele cronice virale B,C (risc de 30 de ori mai
mare)

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161

Factori rasiali i genetici


Frecvena bolilor hepatice induse de alcool este mai
mare la brbaii afroamericani i hispanci, nelegat de
cantitatea de alcool consumat
Exist predispoziie genetic pentru alcoolism i pentru
afectare hepatic
De exemplu : copii adoptai, care provin din familii
alcoolice - dependen de alcool mai frecvent
comparativ cu cei adoptai care nu provin din familii
alcoolice
Polimorfismul genetic este implicat n metabolismul
alcoolului ( alcooldehidrogenaza,
acetaldehiddehidrogenaza i sistemul citocrom P450)

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Denutriia, carenele proteice i hipovitaminozele


preexistente sunt accentuate de consumul de alcool
accelereaz instalarea i decompensarea cirozei i
apariia hepatocarcinomului

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Consumul de medicamente hepatotoxice


(acetaminofenul, hidrazida, droguri diverse)
poteneaz efectele nocive ale alcoolului
precipit instalarea cirozei hepatice

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Obiceiuri:

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Tipul de alcool consumat. Berea i buturile spirtoase sunt


mai nocive comparative cu vinul

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Consumul de buturi alcoolice n afara meselor este mai


periculos dect n timpul meselor

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Riscul de apariie a cirozei hepatice crete n cazul unui


consum:
> 60 80 g alcool/ zi la brbai i > 20 g alcool/ zi la
femei, mai mult de 10 ani
!1 unitate de alcool = 8 g de alcool
Riscul de hepatocarcinom crete dup consum > 60 g
alcool, mai mult de 10 ani, n contextul factorilor de risc

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162

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Diagnostic

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Anamneza + examen clinic + examen biochimic


+ explorare imagistic PBH

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Anamneza
consum de alcool (alcool dependena ) + cuantificare factori de
risc
chestionare pentru alcool dependen i abuzul de alcool :
AVAIT Alcohol Use Disorders Identification Test, MAST
Michigan Alcoholism Screening Test, chestionarul CAGE

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CAGE - cel mai folosit i cel mai simplu


- 4 ntrebari, un rspuns afirmativ =1 punct.
- > 2 puncte pacient cu probleme cu consumul de
alcool
Cele 4 ntrebri care formeaz chestionarul CAGE sunt:
ai simit nevoia s oprii (Cut) consumul de alcool?
suntei deranjat (Annoyed) de afirmaia c avei o problem
cu alcoolul?
v simii vinovat(Guilty) datorit consumului excesiv de
alcool?
trebuie s consumai alcool dimineaa cnd v trezii(Eye
opener)

Examenul clinic obiectiv

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Afectarea hepatic parte din afectarea poliorganic din


alcoolismul cronic (cardiomiopatia alcoolic, pancreatita
alcoolic, neuropatia alcoolic etc.)

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Examenul clinic - stadiului evolutiv al bolii hepatice cronice


(steatoz hepatic ciroz alcoolic complicat) + semne
specifice consumului de alcool (contractur Dupuytren,
hipertrofia parotidelor, feminizare etc)

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Umoral biochimic

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ALT, AST, AST/ALT = 2-3


macrocitoz (VEM>100 3)
scderea folailor : malnutriie, scderea absorbiei intestinale
excluderea altor etiologii ale bolii hepatice

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163

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Explorri imagistice

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nu precizeaz etiologia
evideniaz stadiul evolutiv al afeciunii hepatice :
decompensarea cirozei, hepatocarcinom, etc
explorarea de prim intenie - echografia
CT, RMN - n cazuri selecionate

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PBH
etiologie incert a afeciunii hepatice
dac exist asociat bolii hepatice alcoolice o alt afeciune
hepatic

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Diagnostic diferenial - afeciuni hepatice cu alt


etiologie

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Complicaii ale cirozei hepatice, indiferent de etiologie

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Evoluie i prognostic

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Scorul Maddrey de prognostic - 4,6 x (timpul de


protrombin pacient(sec) - timpul de protrombin control
(sec)) + bilirubina (mg/dl)
severitate boal hepatic, prognostic de supravieuire
decizie terapeutic
scor Maddrey > 32 - evoluie sever, risc ridicat de
mortalitate n 30 zile (30-50%)

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Tratament

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Abstinena - cheia terapeutic n boala hepatic alcoolic

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Alimentaia
scop: diminuarea efectelor malnutriiei proteocalorice i
vitaminice (thyogamma, Mg, vitamine B,C,E,A etc)
n stri grave alimentaie enteral i parenteral
Corticoterapia - boala hepatic alcoolic i encefalopatia
(fr coafectarea altor organe sau complicaii hepatice HDS, insuficien renal, etc)
- 40 mg/zi, 4 sptmni, cu scderea dozei timp de alte 2 4 sptmni sau oprirea administrrii n funcie de evoluie

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164

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Pentoxifilina 400 mg x3/zi - previne apariia sindromului


hepatorenal la pacienii cu scor Maddrey > 32

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Enteroceptul i alte antiTNF necesit studii pentru a putea fi


recomandate n hepatita alcoolic

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Transplantul hepatic
- dup o perioad de abstinen i consimmnt de meninere
a acesteia indefinit

- aceleai indicaii ca i n celelalte etiologii ale CH

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165

166

HEPATITELE AUTOIMUNE
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Definiie i date generale

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proces inflamator hepatic autontreinut, cu etiologie


necunoscut, caracterizat prin hepatit de intefa,
hipergammaglobulinemie i autoanticorpi hepatici
HAI - 11-23% din totalul hepatitelor cronice
raportul F/B=3,6/1, fr distribuie preferenial legat de
vrst sau grupuri etnice
au evoluie paucisimptomatic, >30% din cazuri sunt n
stadiul de ciroz la primul diagnostic
rspunsul la tratament identic - indiferent de vrst, sex
incidena n Europa: 0,1 1,9/105 , prevalena 5-20/105
riscul de HCC la 5 ani 4-7%
reprezint 2,6% i 5,9% din totalul indicaiilor de
transplant hepatic din Europa respectiv SUA
HAI poate reapare la 1- 8 ani dup transplant (n medie 2
ani), n special la cei care nu au primit tratament
imunosupresor corect

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Diagnostic pozitiv (1 -3)


1. Simptome clinice:
- orice form de hepatit cronic fr etiologie

- simptome nespecifice (astenie, artralgii, sindrom dispeptic


trenant)

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- semne sau simptome ale altor afeciuni autoimune asociate


(de la tiroidit cu hipo- sau hiperfuncie, RCUH, DZ, vitiligo,
miastenia gravis etc.)

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Examen obiectiv - concordant stadiului evolutiv: stigmate de


suferin hepatic hepatosplenomegalie icter ascit

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167

2. Date de laborator i serologice

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Creterea transaminazelor, fosfatazei alcaline,


gamaglobulinelor i IgG
Prezena autoAc:
- Ac antinucleari (ANA)
- Ac anti-fibr muscular neted (ASMA)
- Ac anti microsom M1/ficat/rinichi (anti-LKM1 >1/80)
- Ac anti-antigen solubil hepatic (anti SLA)
- Ac anticitosol tip 1 hepatic (anti-LC1)

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3. Puncia biopsie hepatic:

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- hepatit de interfa + inflitrat limfoplasmocitar n


spaiul port + arii de necroz hepatocitar (piecemeal
necrosis)
- hepatocitele - degenerescen vacuolar, canalicule
biliare de neoformaie, corpi acidofili

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Diagnostic diferenial

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Se exclud afeciuni hepatice cu alt etiologie:


Hepatitele virale acute i cronice A,B,C
Steatohepatitele
Consumul recent de medicamente hepatotoxice sau de alcool
Boala Wilson, hemocromatoza
Afeciuni autoimune hepatice: ciroza biliar primitiv, colangita
sclerozant primitiv

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Forme clinice de HAI

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Tip I - caracteristici principale:

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80% din totalul HAI se ncadreaz n tipul I


hipergamaglobulinemie
ANA, ASMA prezeni
foarte frecvent la femei, peste 30 ani ( 80%)
asociaz alte afeciuni imune: tiroidit, boal celiac,
RCUH, eritem nodos, artrit reumatoid etc)
evoluie paucisimptomatic; la momentul diagnosticului
>25% sunt n stadiul de ciroz
Prezena anti-SLA posibilitate de recdere la oprirea
corticoterapiei

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168

Tip II- caracteristici principale:

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afecteaz preponderent copiii


imunglobulinele - valori extrem de crescute
asociaz alte afeciuni imune
evolueaz extrem de frecvent spre ciroz
prezint LKM1 i/sau LC1

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Tipul III Ac SLA - considerat n prezent o variant a tipului I

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Sindroame overlap (suprapunerea a dou afeciuni


hepatice)
prezena simultan a criteriilor clinice, umoral biochimice,
serologice de HAI i frecvent de ciroz biliar primitiv sau
colangit sclerozant primitiv
relativ rar sindromale overlap asociaz la HAI sindroame de
colestaz, hepatit cronic
au evoluie nefavorabil comparativ cu HAI iar tratamentul (pe
loturi mici de pacieni) asociaz la cel standard al HAI- acid
ursodeoxicolic

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Criterii pentru tratamentul imunosupresiv

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Absolute:
ALT 10N
ALT 5N + gammaglobuline 2N
Histopatologie - necroz n punte sau multiacinar
Simptome (artralgii, astenie) care determin incapacitatea
calitii normale a vieii
Relative:
Simptome (astenie, artralgii, icter etc.)
Creterea ALT, gamaglobuline < criteriile absolute
Hepatit de interfa
Nu este indicat n ciroza inactiv, comorbiditi severe sau
intoleran

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Tratamentul standard

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3 scopuri principale:
inducere i meninerea imunsupresiei (cu minime efecte
adverse)
prevenirea i tratamentul cirozei hepatice

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Monoterapie (Prednison)
Biterapie (Prednison cu Azatioprin)
- se prefer biterapia cu monitorizare ntruct efectele
secundare sunt reduse comparativ cu monoterapia

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169

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Tratamentul standard

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Spt 1: - monoterapie ( prednison ) - 60 mg


- terapie combinat ( Ps + AZT)- 30 mg + 50-150 mg
Spt 2: - monoterapie ( prednison ) - 40 mg
- terapie combinat ( Ps + AZT)- 20 mg + 50-150 mg
Spt 3: - monoterapie ( prednison ) - 30 mg
- terapie combinat ( Ps + AZT)- 15 mg + 50-150 mg
Spt 4: - monoterapie ( prednison ) - 25 mg
- terapie combinat ( Ps + AZT) - 15 mg + 50-150 mg
Spt 5: - monoterapie ( prednison ) - 20 mg
- terapie combinat ( Ps + AZT)- 10 mg + 50-150 mg
Terapia de ntreinere - monitorizare:
- monoterapie Ps 10 20 mg
- biterapie Ps sub 10 mg + AZT 50 mg

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Efectele adverse ale tratamentului standard

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Efecte adverse ale corticoterapiei: cosmetice (acnee,


facies Cushingiod, vergeturi), obezitate, osteoporoz,
psihoz, depresie, DZ, cataract, hipertensiune arterial

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Efecte adverse ale azatioprinei: greuri, vrsturi,


dureri abdominale, hepatit toxic, pancreatit, erupii
cutanate, artralgii, mialgii, leucopenie, teratogenicitate,
risc >1,4 pentru cancere extrahepatice

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Tipuri de rspuns n HAI (1-5)

_____________________________________

1.Complet:
- clinic - absena simptomatologiei subiective
- biochimic: bilirubin, albumine, gamma-globuline
normale, ALT<2N
- histologic (remisiune histologic: histologie normal,
hepatit periportal minim)
Durata tratamentului: 2 4 ani!
Conduita:
- se scade prednisonul treptat pn se ntrerupe
- se ntrerupe azatioprina
- se monitorizeaz pentru recdere (transaminaze,
gammaglobuline, bilirubin etc.)

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2. Incomplet:
- ameliorare parial sau lipsa ameliorrii clinice
biologice, histologice
- lipsa rspunsului complet la 3 ani de la iniierea
tratamentului
Conduita: se continu indefinit tratamentul cu doze minime
(fr efecte adverse)
3. Eec:
- agravare clinic, biologic, histologic n timpul
tratamentului imunosupresiv
- creterea transaminazelor
- apariia icterului, ascitei sau encefalopatiei
Conduita: doze mari de prednison (60mg) sau combinaii
(Ps 30mg+AZT 150mg); se reduc dozele lunar (10mg Ps i
50mg AZT); doza de meninere se stabilete funcie de
rspuns
n caz de eec se indic transplantul hepatic

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4.Toxicitatea medicamentelor datorat efectelor adverse


(citopenii severe, supresie medular) - se continu
terapia cu dozele tolerate de pacient
5. Recdere dup ntreruperea tratamentului: recurena
simptomelor i modificrilor biochimice dup ntreruperea
terapiei + hepatit de interfa la PBH
- apare n 50-86% din cazuri
- factori predictivi: ntreruperea prematur a terapiei,
prezena hepatitei periportale, ciroz hepatic n timpul
tratamentului (87-100%)
- dup prima recdere se menine tratamentul indefinit
cu AZT 20mg sau prednison 7,5 - 10mg/zi n monoterapie

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Alte posibiliti terapeutice

_____________________________________

Inhibitorii de calcineurin ( ciclosporina i tacrolimus)


Ciclosporina: cazuri refractare sau intoleran la tratamentul
standard, efecte secundare multiple (nefrotoxicitate,
hipertensiune arterial etc)
Tacrolimus: toxic, scump, experien redus
Mycofenolat mofetil - experien redus, nu are n prezent
stabilit profilul de siguran, dozele, monitorizarea
Budesonidul - corticoid de generaia a II-a, se folosete n
forme uoare de HAI cu contraindicaii sau intoleran la
prednison
Ciclofosfamida, metotrexatul, acidul ursodeoxicolic au
fost folosite pe loturi mici de pacieni, nu au fost cuantificate
ca eficien, posologie sau profil de siguran

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171

172

CIROZA HEPATIC
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Definiie

proces cronic difuz, caracterizat histologic prin


necroz + fibroz + regenerare nodular cu pierderea structurii
normale a ficatului

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Clasificare

_____________________________________

- morfologic
- etiologic

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Clasificare

_____________________________________
_____________________________________

1.Morfologic

_____________________________________
- micronodular (Laennecs) - noduli <3 mm, cel mai frecvent

n etiologia alcoolic
- macronodular - noduli > 3mm, n etiologia viral B, C
- mixt - asociaz ambele aspecte

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173

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Clasificare

_____________________________________

2. Etiologic

_____________________________________

a.Ciroza alcoolic anamnez pozitiv + stigmate clinice


( contractur Dupuytren, polineneuropatie), raport AST/ALT,
macrocitoza, GGTP etc

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b. Ciroza viral B, C, D
B Ag HBs, Ac anti HBc, viremie
C Ac anti VHC, viremie
D Ac anti VHD, viremie

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c. Ciroza din bolile colestatice ciroza biliar primitiv ( AMA,


IgM, PBH), ciroza biliar secundar ( MRCP, ERCP, PBH),
colangita sclerozant primitiv ( MRCP, ERCP, PBH)

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_____________________________________

d. Ciroza post hepatite imune: ANA, Ac tip IgG antifibr


muscular neted, PBH

_____________________________________

e. Ciroza vascular ciroza cardiac: EKG,ecocardiografie


- Budd- Chiari: ecografie, Dopler, CT,
RMN
f. Ciroza metabolic
hemocromatoz (fier, mutatia genei HFE)
- Boala Wilson (cupru seric, urinar, ceruloplasmina, inel Keiser
Fleisher, PBH)
- deficit de 1 antitripsina (nivel 1 antitripsina, PBH)
- steatohepatita nonalcoolic, nonviral (PBH)
- criptogenic excludere steatohepatit, PBH

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Diagnosticul n forma compensat

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n peste 33% din cazuri pacientul este asimptomatic,


capacitatea de munc pastrat, diagnosticul fiind
ntmpltor
istoric lung de suferin hepatic

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Examen obiectiv

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- poate fi normal sau stigmate de afeciune cronic


hepatic
- stelue vasculare, circulaie colateral abdominal,
contractur Dupuytren etc
- hepatosplenomegalie

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174

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Explorri paraclinice

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Umoral biochimic:
sindrom de citoliz ( ALT, AST, LDH, fier, vitamina B12,
ornitin carbamil transferaz)
sindrom bilioexcretor ( pigmeni biliari, bilirubina, acizi
biliari, urobilinogen, stercobilinogen)
sindrom de hiperactivitate mezenchimal ( electroforeza
proteinelor, imunoglobulinele serice)
sindrom hepatopriv ( hipoproteinemie cu hipoalbuminemie,
hipocolesterolemie, scderea indicelui de protrombin)

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Aceste explorri nu certific diagnosticul diferenial ntre


hepatita cronic i ciroza hepatic; pot fi sugestive pentru
CH: trombocitopenie, inversarea raportului AST/ALT
(creterea AST)
Pentru acuratee, diagnosticul trebuie s coroboreze anamneza
+ examenul obiectiv + umoral - biochimic + ecografic +
endoscopic

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Explorarea imagistic

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Ecografia
Ficat - pierderea structurii normale hepatice + hipertrofia
lobului caudat (N: max 35 mm). Lobul caudat > 40mm ciroza hepatic n 2/3 din cazuri, n context clinic
cunoscut
Splin - 80% din pacienii cu splenomegalie > 15 cm (N:
12cm)
Semne de hipertensiune portal Doppler (excludere
tromboze VP,VS) - VP > 12mm, VS > 8mm preaortic,
repermeabilizare ven ombilical
Colecist: dedublare perete vezicular (hipoalbuminemie,
staz limfatic, HTP) i litiaz biliar vezicular (de obicei
asimptomatic)
monitorizare HCC: apariie tratament ( alcoolizare,
radiofrecven, etc.) recidiv
8

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Ecografia Doppler
permeabilitate vene suprahepatice, tromboz complet/
incomplet ven port vascularizaie formaiuni hepatice

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Computer tomografia i rezonana magnetic nuclear


informaii suplimentare; cazuri selecionate

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9

175

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Elastografia impulsional hepatic ( Fibroscan)


metod non-invaziv
determin duritatea (elasticitatea) hepatic
CH compensat sensibilitate 87 %, specificitate 91%
pentru valori > 14 kPa)
nu se poate efectua la pacienii cu ascit
valoare predictiv pentru apariia complicaiilor din CH
( VE, HCC, decompensare)

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Puncia biopsie hepatic


percutan (cel mai frecvent) / transjugular
confirm diagnosticul

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Tratament

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Msuri generale

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6-7 mese pe zi, evitarea postului prelungit


35-45 kcal/kgc/zi, proteine 0,8-1gr/kgc/zi; restricie proteic
perioade scurte ( EHP)
corectare deficite din CH: anemie macrocitar (folai i B12),
neuropatie (piridoxina, tiamina, B12), confuzie, ataxie
(thiogamma), lipsa adaptrii la ntuneric i deficitul de
vitamina A ( vitamina A)
controlul greutii (obezitatea accelereaz fibroza) diet,
exerciiu fizic, schimbarea obiceiurilor alimentare
renunare la alcool i fumat (aceti factori fibroza
hepatic, incidena HCC; alcoolul este contraindicaie pentru
transplantul hepatic)

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igiena dentar - prevenire infecii


evitarea medicamentelor hepatotoxice (citirea prospectului!)
imunizarea. Se recomand:

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- vaccinuri VHA, VHB - precoce - eficiena scade paralel cu


evoluia bolii (n CH avansat - doz dubl)
-

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grip - vaccinare anual

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osteoporoza - evaluare i tratament

monitorizarea afeciunilor asociate - creterea calitii vieii


pacientului cirotic

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12

176

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COMPLICAIILE CIROZEI
HEPATICE
HEMORAGIA DIGESTIV
SUPERIOAR PRIN HIPERTENSIUNE
PORTAL

Evoluia hipertensiunii portale n ciroza hepatic


Hipertensiunea portal (HTP): sindrom frecvent ntlnit
caracterizat prin creteri patologice ale presiunii n sistemul
venos portal ( N = 5 - 10 mmHg)
Gradientul presional portal: valoarea presiunii portale se
exprim ca fiind gradientul ntre presiunea portal i cea
din vena cav inferioar
Evoluia HTP din ciroza hepatic are 3 etape n funcie
de gradientul portal:
Gradient presional portal >5 dar <10 mmHg fr
manifestri clinice
Gradient presional portal >10 mmHg dar <12 mmHg, cu
manifestri clinice de HTP: varice esofagiene, ascit ,
peritonit bacterian spontan (PBS), sindrom
hepatorenal (SHR).
Gradient presional portal 12 mm Hg: apare HDS prin
ruperea varicelor

n ciroza hepatic :
procentul anual de apariie a VE 5 -7 %
1/3 pacieni cu CH fac HDS prin efracie variceal
mortalitatea la fiecare sngerare este de 20%
riscul de resngerare 25%
60% din cirotici au VE n momentul apariiei ascitei

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EDS este singura metod de evideniere a HTP din CH


se efectueaz n toate CH - metod de screening pentru VE
se repet:
- dup 3 ani n CH fr VE la examinarea anterioar
- la 2 ani n VE mici
- la 1 an n cazurile selecionate ( consum de alcool,
accentuarea insuficienei hepatice, stigmate endoscopice care
atest risc de sngerare nalt la EDS precedent)

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177

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Tratamentul HDS prin efracie


variceal

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I. Prevenia primar a HDS prin efracie variceal


II. Tratamentul HDS active prin efracie variceal
III. Prevenirea recurenelor hemoragice dup oprirea
spontan sau terapeutic a primei HDS variceale

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I. Prevenia primar a HDS prin efracie


variceal
A. Farmacologic
B. Endoscopic

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A. Tratamentul farmacologic

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Nu exist n prezent substana ideal care s scad


rezistena vascular, s menin fluxul portal i s
amelioreze funcia hepatic!
1. Propranolol (aspirina hepatologului):
- blocant neselectiv 1, 2, vasoconstrictor splahnic
- doza: 40 - 300 mg /zi , astfel nct frecvena cardiac s
scad cu 25%
- scade presiunea portal cu 20 % sau gradientul de
presiune portal <12 mmHg Atenie: numai n 30 - 40 %
este eficient
Efecte secundare : astenie, fenomen Raynaud,
bronhospasm, DZ
Atenie: nu se ntrerupe brusc precipit sngerarea
variceal

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2. Nadolol 80mg /zi, Timolol, Carvedilol

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20

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B. Tratamentul endoscopic

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ligatura > scleroterapia


se practic profilactic primar n 3 situaii:
- dac exist risc crescut de sngerare VE mari cu
spoturi roii
- intoleran sau contraindicaii pentru blocante (~30%)
- rspuns insuficient la blocante (presiunea portal nu
diminu cu 20 % sau gradientul presional portal nu scade sub
12 mmHg)

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178

II. Tratamentul HDS active prin efracie


variceal

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oprirea sngerrii
Scop: corectarea hipovolemiei
prevenirea complicaiilor sngerrii active
prevenirea deteriorrii funciei hepatice

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1.Msuri generale
- asigurarea 2 -3 linii de abord venos
- intubare orotraheal prevenirea aspiraiei
- corectarea hipovolemiei ( soluii coloidale, albumin)
- prevenirea infeciei bacteriene (precipit resngerarea
imediat i crete mortalitatea intraspitaliceasc). Se
administreaz cefalosporine de generaia a-III-a
- transfuzii de snge
Scopul transfuziei - stabilizarea Hb la 8 g/dl.
Overexpension poate determina creterea presiunii
portale i implicit resngerarea
- meninerea funciei renale (apariia sindromului hepatorenal
deces n 95 % cazuri)
- tratamentul EHP - lactuloz, rifaximin
- nutriie parenteral adaptat strii pacientului

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2.Tratament farmacologic

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Se instituie premergtor endoscopiei dac exist suspiciune de


hemoragie variceal
Se menine 5 zile pentru prevenirea resngerrii imediate, avnd
efect sinergic cu terapia endoscopic

Terlipresin ( analog sintetic vasopresin)


- i.v. lent la 4 ore n doze de 1 -2 mg n funcie de greutate timp de
5 zile
- efecte secundare vasoconstricie coronarian i generalizat.
Atenie la pacienii cu factori de risc cardiac, aritmii, hiponatremie,
acidoz lactic!

Ocreotid (analog sintetic de sandostatin)

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- perfuzie i.v. continu 25 g/h, 5 zile, precedat de 50 g bolus


- efecte secundare: puine ( greuri, dureri abdominale,
modificarea glicemiei bazale)

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179

3.Tratament endoscopic

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Se practic la toi pacienii cu sngerare activ prin efracie


variceal

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Scleroterapia endoscopic
- injectarea ( intra i/sau paravariceal) a unui agent
scerozant; n prezent nu exist un agent sclerozant optim
sau ideal
- hemostaza se produce n 80 90% din cazuri
- complicaii n 10 -20 % din cazuri: stenoze, perforaii,
hemoragii, ulcere
Ligatura endoscopic
- eficien similar cu scleroterapia, efecte secundare mai
puine

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25

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4.Tamponada mecanic: tamponament cu sond


Sengstaken-Blakemore
- greu acceptat de pacient
- hemostaz n >90% din cazuri pentru minim 24 - 48 ore
- recidiv n > 50 % din cazuri
- complicaii - ischemia gastric / esofagian
- ruptura traheei, obstrucia laringelui, esofagului
- aspiraia

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5.unt porto-sistemic transjugular intrahepatic


(TIPS)
Principiu: se introduce o endoprotez transjugular ntre vena
port i hepatic cu scderea presiunii portale
Indicaie:
- dac tratamentul hemostatic farmacologic i endoscopic
ncercat de 2 ori a euat

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Hemostaz 90 % din cazuri

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Complicaii (10% - 20%) - encefalopatie

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180

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6.Obliterare percutan transhepatic - varicele


gastrice

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- sclerozare sau embolizare


- controleaz 70% din sngerri

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7. unturi porto-sistemice chirurgicale

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- mortalitate - 40% (efectuat n urgen)


- nu prelungesc supravieuirea
- scad perfuzia hepatic
- precipit instalarea insuficienei hepatice
- encefalopatie hepato-portal
- unt selectiv cel mai frecvent: unt splenorenal distal

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8. Alte metode chirurgicale

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- devascularizare esofag distal/stomac proximal


- splenectomie
- mortalitate foarte crescut

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9.Transplantul hepatic
- curativ

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- la pacienii cu boal terminal

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29

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HDS prin efracia varicelor gastrice

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25 % din ciroze au varice gastrice


HDS prin varice gastrice reprezint 10 % din hemoragiile
variceale, cu resngerare n jumtate din cazuri
prin analogie, n linii mari este asemantor cu cel din VE,
dar mai puin eficient

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181

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HDS prin gastropatia portal hipertensiv

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forma acut exteriorizat prin hematemez i/sau


melen
forma cronic scderea Hb cu 2 g/dL la evaluarea la 6
luni a pacientului cirotic ( se exclude consumul de AINS)
Diagnostic endoscopic : aspect mozaicat, vrgat, cu
sngerare difuz sau n spoturi
+
- histopatologic dilatarea capilarelor i
venulelor cu unturi arteriovenoase n
submucoas, fr leziuni inflamatorii
Tratament: este cel al HTP

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III. Prevenirea recurenelor hemoragice dup


oprirea spontan sau terapeutic a primei
HDS variceale

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Argument: dup un prim episod de HDS prin efracie


variceal oprit spontan sau terapeutic, resngerarea este
de 60 -70 % n urmtorii 2 ani, cu mortalitate de 30 %
se instituie ct mai repede posibil, din a-6 a zi de la
episodul de sngerare variceal oprit spontan sau
terapeutic
este farmacologic ( propranolol) i/sau endoscopic
( ligatur > scleroterapie)

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Se practic la urmtoarele categorii de pacieni

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Ciroz fr terapie profilactic


primar

blocant i/sau ligatur

Ciroz cu sngerare sub terapie cu


blocant

blocant + ligatur

Contraindicaii sau intoleran la


blocante

Ligatura este preferat pentru


prevenirea resngerrii

Eec al profilaxiei secundare

TIPS; transplant hepatic

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COMPLICAIILE CIROZEI
HEPATICE

ASCITA

34

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ASCITA

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(askos = geant, sac)

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acumulare de lichid n cavitatea peritoneal


este cea mai frecvent complicaie a CH
riscul de apariie la pacienii cirotici - 5 -7 % ~60% din
pacienii cu CH compensat vor face ascit la 10 ani de la
diagnostic
de la apariia ascitei supravieuirea medie fr transplant
hepatic scade la 50 % la 2 ani
n ascita refractar supravieuirea la 1 an este de 25 %
modificrile hemodinamice induse de ascit precipit alte
complicaii ( hiponatremie, peritonita bacterian spontan,
sindrom hepatorenal) care scad supravieuirea

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35

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Diagnostic clinic

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Anamneza: : istoric de boala hepatic, debut insidios prin


distensie abdominal, cretere n greutate, edeme, hernie
ombilical

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Examenul fizic:
- abdomen mrit de volum
- icter
- circulaie colateral abdominal
- stelue vasculare
- eritem palmar, plantar
- hernie ombilicala
- edem scrotal sau penian
- matitate deplasabil pe flancuri , semnul valului
- hepatosplenomegalie

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183

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36

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Explorri paraclinice

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A . Funcia hepatic:

Alterarea celor
4 sindroame hepatice

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sindromul de citoliz
sindromul bilioexcretor
sindromul hepatopriv
sindromul de iritaie mezenchimal

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B. Radiografie abdominal pe gol


- tergerea umbrei psoasului

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C. Ecografie
- evidenierea precoce a lichidului de ascit acumulat n abdomen
(100ml) cu informaii asupra volumului, vechimii ascitei
- semne de ciroz hepatic i eventuale complicaii (hepatom,
tromboz de ven port etc)

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D. Tomografie computerizat n cazuri selecionate

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E. EDS - varice esofagiene, gastropatie portal hipertensiv

37

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F. Paracenteza diagnostic

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- locul puncionrii linia spino-ombilical sng

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- complicaii(1%) - perforaia intestinului


- hemoragie
- fistul cu prelingere continu de lichid
- se face n 4 situaii:
- ascit la primul diagnostic
- ciroz + ascit + spitalizare + semne de infecie
- ciroz + ascit + deteriorarea strii generale
- ciroz + ascit + deteriorarea biochimic pe parcursul
internrii
- ascita din HTP are gradient albumin seric/albumin lichid
de ascit > 1,1; acesta se coreleaz n 97% din cazuri cu HTP

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Diagnostic diferenial

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obezitate, meteorism, glob vezical, uter gravid, tumori

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etiologia ascitei:
hepatic: ciroza, insuficiena hepatic, hepatita
alcoolic, tromboza portal, sindromul Budd Chiari,
metastazele hepatice
extrahepatic: insuficiena cardiac congestiv,
hipertensiunea pulmonar, sindromul nefrotic,
tuberculoza, carcinomatoza peritoneal, mixedemul,
pancreatita

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184

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Diagnosticul diferenial al ascitei n funcie de


gradientul albumin seric / albumina n lichidul de
ascit
I. albumina seric /albumina ascit > 1,1 g/dl: ciroza
hepatic, hepatita alcoolic, ascita cardiac, metastazele
hepatice, insuficiena hepatic fulminant,tromboza venei
porte, sindromul Budd-Chiari, mixedemul

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II.albumina seric /albumina ascit < 1,1 g/dl:


carcinomatoza peritoneal, TBC peritoneal, sindromul
nefrotic, cauze rare (ascita biliar, pancreatic, boli de
colagen)

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Tratamentul ascitei din CH

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Diuretice: - antialdosteronice (spironolactona)


- aciune la nivelul ansei Henle ( furosemid)
alegerea dozei: individualizat, cu msurarea zilnic a
diurezei, concentraiei electroliilor (plasmatic, urinar),
evaluarea evoluiei edemelor i greutii
spironolacton 50, 100 mg ( maxim 400 mg) furosemid 40
mg (maxim 160 mg)
dozele se cresc progresiv la 5 -7 zile, pn la cele maxime

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- encefalopatie
- Na seric < 120 mEq/L dup restricie hidric
Diureticele se opresc:
- creatinina > 2 mg/dl
- hiperpotasemie, acidoz metabolic( spironolactona)

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Ascita refractar

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5-10 % din ascite


Definiie: ascita care nu rspunde la doze maxime de
diuretice (400 mg spironolactona, 160 mg furosemid) sau n
care dozele maxime nu pot fi administrate datorit efectelor
adverse (hiperkaliemie, hiponatremie, EHP, insuficien
renal)

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Factori favorizani
- infecii asociate
- tromboz de vena port sau hepatic
- hemoragie digestiva superioara
- PBS
- carcinom hepatocelular
- malnutriie
- factori hepatotoxici: alcool, acetaminofen
- factori nefrotoxici AINS, etc

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Tratamentul ascitei

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grad 1 ( ascit decelabil ecografic)


- restricie sodat ( < 2 g/zi Na Cl)
moderat ( distensie simetric abdominal)
- diuretice : Spironolactona 50 200 mg/zi max 400 mg
Furosemid 20 - 40 mg/zi max 160 mg/zi
- scdere ponderal (0,5 Kg/zi la cei fr edeme i 1 kg/zi
la cei cu edeme)
masiv sub tensiune
- paracentez voluminoas > 5 l + 6-8 g/l albumin

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refractar
paracenteze + albumin 6 -8 g/litru lichid extras
diet hiposodat, restricie hidric
unt porto sistemic transjugular
Ideal : Transplant hepatic
- supravieuirea la 12 luni la pacienii cu ascit refractar
- 25%
- supravieuirea la 12 luni la pacienii transplantai 70 -75%

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_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

186

COMPLICAIILE CIROZEI
HEPATICE
PERITONITA BACTERIAN
SPONTAN

45

_____________________________________
_____________________________________

Definiie. Etiologie

_____________________________________

infecie monobacterian a lichidului de ascit, la un vechi


cirotic, cu ascit sub tensiune, n absena oricrui factor
de infecie intraabdominal; tratament non chirurgical

_____________________________________
_____________________________________
_____________________________________

prevalena 10 - 30 % din pacienii cu CH

_____________________________________

Germenii frecvent implicai: Escherichia Coli i


Klebsiella Pneumoniae

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Mecanisme patogene n PBS

_____________________________________
_____________________________________

Sursa de infecie: colonul, tractul urinar, respirator, pielea


3 mecanisme patogene:

_____________________________________
_____________________________________

Translocarea bacterian din intestin n ganglionii


limfatici mezenterici

_____________________________________
_____________________________________

Scderea
activitii
fagocitare
n
sistemul
reticuloendotelial, considerat mecanism esenial n
colonizarea i persistena bacteremiei
n ciroza
hepatic

_____________________________________
_____________________________________
_____________________________________

Reducerea mecanismelor de aprare


lichidul de ascit

bacterian n

_____________________________________
_____________________________________

47

_____________________________________

187

_____________________________________

Factorii precipitani n PBS

_____________________________________
_____________________________________

Confirmai:

_____________________________________

insuficien hepatic sever, clasa C Child


ascit sub tensiune
HDS
concentraia proteinelor n lichidul de ascit < 1 g/dL
episod anterior de PBS
Na < 130 mEq/L
creatinin > 1,5 mg/dl

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

48

_____________________________________

_____________________________________
_____________________________________

Factori posibili, dar neconfirmai:


infecii tract urinar
cateterismul vezicii urinare
cateterism intravenos
paracentezele voluminoase

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Factori improbabili: paracenteza, endoscopia hemostaza


endoscopic, hepatocarcinomul

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Diagnosticul pozitiv n PBS

_____________________________________

anamneza: pacient cu ciroz hepatic cu evoluie


ndelungat, cu ascit sub tensiune

_____________________________________

simptome nespecifice, frecvente anun PBS: vrsturi,


diaree, encefalopatie hepatoportal, hemoragie digestiv
superioar

_____________________________________

_____________________________________

_____________________________________

simptome frecvent ntlnite: febra, deteriorarea mintal,


insuficiena renal progresiv

_____________________________________

simptome rar ntlnite n prezent datorit cunoaterii


afeciunii i tratamentului profilactic: septicemie, oc toxicoseptic
Investigaii paraclinice sanguine: leucocitoz, afectare
funcional hepatic sever (insuficien hepatic clasa C
Child) i insuficien renal n 1/3 din cazuri

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

50

188

_____________________________________

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

n prezena acestor simptome, diagnosticul de


certitudine : analiza lichidului de ascit:
polimorfonucleare (PMN) i cultur

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
51

Diagnostic pozitiv, diferenial i de form clinic

_____________________________________

_____________________________________
_____________________________________
_____________________________________

Clasic descris de CONN


- lichid de ascit cu PMN > 250 /mm3, cultur pozitiv
monobacterian

_____________________________________
_____________________________________
_____________________________________

Ascita neutrocitic i culturi negative


lichid de ascit cu PMN > 250 elemente /mm3 i culturi
negative

_____________________________________
_____________________________________
_____________________________________

Bacterascita monobacterian nonneutrocitic:


lichid de ascit cu PMN sub 250 elemente/mm3 i culturi
pozitive pentru un singur germene

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Diagnostic diferenial

_____________________________________

Diagnosticul de peritonit bacterian secundar prin


perforarea unui viscer (beneficiaz de tratament
chirurgical!)

_____________________________________
_____________________________________

PMN > 250 /mm3


pluribacterian
proteine totale > 1g/dl
glucoz > 50 mg/dl
LDH > 225 UI/ml
la tratament PMN i culturile se normalizeaz n 48 h n PBS, nu
i n cea secundar

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Bacterascita plurimicrobian: < 250 PMN, pluribacterian,


apare (1/1000 cazuri) dup puncionarea intestinului n timpul
paracentezei diagnosticeparacentezei diagnostice:
53

189

_____________________________________
_____________________________________
_____________________________________

_____________________________________

Profilaxia apariiei PBS

_____________________________________
_____________________________________

status nutriional bun


consum (cel puin) discontinuu de alcool
scderea duratei de spitalizare n ciroza hepatic
manevrele invazive - numai dac sunt necesare
prevenirea altor complicaii (encefalopatie hepatoportal,
hemoragie digestiv superioar, decompensare vascular)
care pot precipita apariia PBS
tratamentul cu diuretice previne PBS. Diureticele cresc
activitatea opsoninic a lichidului de ascit indiferent dac
bolnavul are sau nu PBS

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________

Tratamentul n PBS

_____________________________________

I. Episod acut
II. Profilactic

_____________________________________

I. Episodul acut: PBS se trateaz indiferent de forma clinic !

_____________________________________
_____________________________________

Atenie: dac episodul acut nu este diagnosticat, apar


complicaii letale: oc septic, insufien renal, hepatic
Regul: diagnostic precoce + tratament imediat cu cefalosporine
din generaia a IIIa (penetrare n lichidul de ascit, toxicitate
redus )

_____________________________________

Posologie : Cefotaxim 2g (la 8h ) intravenos sau Amoxiclav 1,2


g x4/zi, timp de 5-7 zile + albumin 1,5 g/Kg c (albumina
scade riscul de apariie a sindromului hepatorenal i a
insuficienei renale la pacienii cu PBS)

_____________________________________

55

II. Tratament profilactic

_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________

_____________________________________

Recurena este de 43% la 6 luni


69% la 12 luni
79 % la 2 ani
3 situaii distincte:

_____________________________________

1. Episod anterior PBS - norfloxacin 400 mg/zi indefinit ( transplant,


deces)
- dac apare rezistena, se administreaz
ciprofloxacin, levofloxacin

_____________________________________

2. Ciroz cu episod anterior de HDS ( 20 50 %)


- cefalosporin gen III 7 zile
- norfloxacin 400 mg/zi indefinit (transplant, deces)

_____________________________________

_____________________________________
_____________________________________

_____________________________________
_____________________________________

_____________________________________
_____________________________________

3. Proteine < 1 g/dl ascit - norfloxacin 400 mg/zi p.o. n timpul


spitalizrii
- ndelungat profilactic

_____________________________________
_____________________________________
_____________________________________

190

_____________________________________

Prognosticul n PBS

_____________________________________

Imediat : favorabil mortalitatea intraspitaliceasc prin PBS

_____________________________________

a diminuat semnificativ (de la 100% 40% 20%) .

_____________________________________

Diagnosticul precoce i folosirea de antibiotice fr efecte

_____________________________________

secundare nefrotoxice a fcut posibil acest lucru.

_____________________________________

Tardiv : grav. La 1 i 2 ani supravieuirea este de 30% i

_____________________________________

respectiv 20%, indiferent de etiologia cirozei, direct

_____________________________________

proporional cu gradul insuficienei hepatice

_____________________________________

Ideal: supravieuitorii unui episod de PBS trebuie evaluai


pentru transplant hepatic

_____________________________________
_____________________________________
_____________________________________

57

191

_____________________________________

COMPLICAIILE CIROZEI
HEPATICE
SINDROMUL HEPATO - RENAL

58

Definiie : insuficien renal funcional, potenial

_____________________________________

reversibil cu/fr transplant hepatic, care apare n ciroza


hepatic cu ascit sub tensiune i insuficien hepatic
sever
Incidena anual este de 8%

_____________________________________

_____________________________________

_____________________________________
_____________________________________
_____________________________________

Factori favorizani:

_____________________________________

infeciile bacteriene
hemoragiile digestive
paracentezele voluminoase (>5 l)
interveniile chirurgicale
medicamentele nefrotoxice

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
59

_____________________________________

_____________________________________

Tipuri de sindrom hepatorenal

_____________________________________

Sindromul hepatorenal tip 1 (acut)

_____________________________________

Factori precipitani: - peritonita bacterian spontan


- consumul de alcool
- HDS
- paracenteze mari repetate
Caracteristici:
- creterea valorii iniiale a creatininei > 2,5 mg/dl
- scderea clearence-ului creatininei endogene la
jumtate n 24 de ore (<20 ml/min).

_____________________________________

Fr transplant hepatic supravieuirea este de 2 sptmni

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

192

_____________________________________

Tipuri de sindrom hepatorenal

_____________________________________
_____________________________________

Sindromul hepatorenal tip 2 (cronic, lent

_____________________________________

progresiv)
- valori ale creatininei serice > 1,5 2,5 mg/dl
- fr transplant hepatic supravieuirea este de 6-812 luni, direct proporional cu gradul insuficienei
hepatice

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
61

Criterii de diagnostic (Baveno IV)

_____________________________________

_____________________________________

Majore:
Afectare hepatic cronic n stadii terminale cu ascit
Creterea creatininei serice > 1,5 mg/dl
Scderea clearanceului de creatinin < 40 ml/min
Absena: strii de oc, infeciilor bacteriene, utilizrii de medicamente
nefrotoxice, pierderilor lichidiene (vrsturi, diaree)
Lipsa de mbuntire a funciei renale la ntreruperea diureticelor i
administrarea a1500 ml de soluie salin izoton
Absena proteinuriei i a oricrei anomalii echografice

_____________________________________

Minore:
Diureza n 24 ore sub 500 ml
Natriureza sub 10 mEq/l
Osmolaritate urinar > osmolaritate plasmatic
Hematurie < 50 elemente/mm3
Natremie<130 mEq/l

_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Diagnostic pozitiv: se pune pe baza criteriilor

_____________________________________

majore +/- cele minore

_____________________________________
_____________________________________

Diagnostic diferenial:

_____________________________________

- orice form de insuficien renal acut

_____________________________________
_____________________________________

Prognostic

_____________________________________

- fr transplant hepatic mortalitate > 90%

_____________________________________
_____________________________________

Tratament profilactic

_____________________________________

- ndeprtarea factorilor favorizani

_____________________________________
63

193

_____________________________________

Tratament: Sindromul hepatorenal tip 1

_____________________________________

I. Ideal transplant hepatic


- sindromul hepatorenal tip 1 este prioritizat pe lista de transplant
- supravieuirea cu transplant este n proporie de 60% la 3 ani
II. Administrarea de ageni vasoconstrictori i albumin
- Terlipresin 0,5-1 mg la 4-6 ore +
- Albumin 1g/kgc/zi urmat de 20-40 mg/zi creatinina < 1,5
mg/dl
III. TIPS (untul portosistemic transjugular)
- normalizeaz funcia renal n 75-90% din cazuri
- se indic la pacienii: fr EHP, bilirubina < 15 mg/dl,
Child-Pugh < 12
- crete supravieuirea la 3,6,12 luni la 64%,50%, i respectiv 22%
IV. Dializa cu albumin
- efect benefic cu supravieuirea la 1 lun de 41%, la 3 luni de
34%

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tratament: Sindromul hepatorenal tip 2

_____________________________________
_____________________________________
_____________________________________

Se indic transplant hepatic


Administrarea de substane vasoconstrictoare i
albumin determin rezolvare iniial n 80% din cazuri;
recidiv n 100% din cazuri
TIPS asigur supravieuirea la 1 an n 70% din cazuri

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

194

COMPLICAIILE CIROZEI HEPATICE


COMPLICAII PORTOPULMONARE
Hipertensiunea portopulmonar
Sindromul hepatopulmonar

66

Hipertensiunea portopulmonar

_____________________________________

Definiie creterea presiunii n artera pulmonar > 25

_____________________________________

mm Hg i a rezistenei vasculare pulmonare >240


dyne/s/m la pacienii cu HTP

Simptome i examen fizic:

_____________________________________
_____________________________________
_____________________________________

stigmate de ciroz hepatic + insuficien cardiac dreapt

Diagnostic paraclinic:

_____________________________________
_____________________________________

crete peptidul natriuretic ( crete n insuficiena


ventricular dreapt)
Radiografia toracic lrgirea conturului arterei
pulmonare
Ecografie Doppler transtoracic hipertrofie ventricular
dreapt, micare paradoxal sept interventricular, presiunii
n VD > 50 mm Hg impune cateterismul inimii drepte

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Diagnostic

_____________________________________

Presiunea n artera pulmonar > 25 mm Hg


Rezistena vascular pulmonar > 240 dyne/s/m

_____________________________________
_____________________________________
_____________________________________

Diagnostic diferenial:

_____________________________________
_____________________________________

Trombembolism pulmonar
Boal pulmonar interstiial
Boal de esut colagenic
Apnee de somn netratat

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

195

Tratament:

_____________________________________

nu se cunoate substana ideal, eficient pentru


tratament
se trateaz convenional - diuretic, tonic cardiac, oxigen
! N.B. atenie la beta blocante
este extrem de important stabilirea diagnosticului i
tratamentului nainte de transplantul hepatic (presiunea
n artera pulmonar se coreleaz cu riscul de deces
posttransplant)
- presiunea n artera pulmonar >50 mm Hg risc de
deces perioperator - 100%
- presiunea n artera pulmonar <50 mm Hg i
>35 mm Hg risc de deces - 50%
- presiunea n artera pulmonar <35 mmHg risc de
deces nul

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Sindromul hepatopulmonar

_____________________________________
_____________________________________

Definiie: hipoxemie prin alterri microvasculare

_____________________________________

intrapulmonare (dilatare capilar i/sau arterial) n


prezena disfunciei hepatice sau HTP
15-30% din pacienii evaluai pentru transplant hepatic
au hipoxemie

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Diagnostic clinic:

_____________________________________

Semne clinice: de hipertensiune portal i dispnee (de


efort, platipnee, ortodexie)
Examen obiectiv: cianoz i degete hipocratice

_____________________________________
_____________________________________
_____________________________________
70

_____________________________________

_____________________________________
_____________________________________

Diagnostic paraclinic

_____________________________________

Evaluarea funciei hepatice


Probe funcionale respiratorii
Radiografia toracic modificri nespecifice
Puls-oximetria test screening noninvaziv (SaO2 < 95%
PaO2 < 70 mmHg); testul are specificitate de 88% i
sensibilitate 100%
Cuantificarea afectrii schimburilor gazoase la nivel
pulmonar se face prin determinarea PaO2. Dac PaO2 < 60
mm Hg prioritizare pe lista de transplant

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

71

196

_____________________________________

_____________________________________

Tratament :

_____________________________________

Administrarea de O2 (nu exist studii randomizate)


Tratament medicamentos nestandardizat, controversat
(aspirin, norfloxacin, pentoxifilin)
Transplant hepatic ameliorarea hipoxemiei n 85% din
cazuri

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Prognostic: n absena transplantului hepatic


supravieuirea este de aproximativ 10,6 luni

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

197

COMPLICAIILE CIROZEI
HEPATICE
CARDIOMIOPATIA CIROTIC

73

_____________________________________
_____________________________________
_____________________________________

Definiie:

" form cronic de disfuncie cardiac la


pacienii cu ciroz hepatic caracterizat prin disfuncie
sistolic la factori de stress i/sau disfuncie diastolic,
asociat cu anomalii electrofiziologice n absena unei
boli cardiace coexistente (Congresul Mondial de
Gastroenterologie Montreal 2005 )

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Elemente caracteristice:

_____________________________________

Entitate distinct de afectarea cardiac indus de consumul


de alcool
Afectarea cardiac din CH este consecina tulburrilor
hemodinamice i neuro-endocrine care evolueaz paralel
cu severitatea bolii hepatice
Apare n CH indiferent de etiologie
Este a-III-a cauz de deces posttransplant
Nu exist un singur test care s o pun n eviden
Cele mai obinuite anomalii sunt:
- alungirea intervalului QT
- raport subunitar ntre umplerea ventricular precoce i
cea tardiv
Nu are tratament specific standard; se tratateaz suportiv +
ameliorarea funciei ventriculare stngi

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

198

COMPLICAIILE CIROZEI
HEPATICE
ENCEFALOPATIA HEPATO
PORTAL (EHP)

76

_____________________________________

Definiie: anomalii

neuropsihice, potenial reversibile la


pacienii cu disfuncie hepatic

_____________________________________
_____________________________________
_____________________________________

Clasificare
EHP minim
modificari ale testelor psihometrice cu examen
neurologic standard normal la pacienii cu ciroz
hepatic
apare n 50- 60% din cirozele hepatice. Are impact
asupra calitii vieii, condusului vehiculelor,
accidentelor navale, rutiere, etc
EHP : alterri neuropsihice la un pacient cunoscut sau
suspectat de afectare hepatic sever

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Clasificarea encefalopatiei hepatice


criteriile West Haven

_____________________________________
_____________________________________

stadiul 0: - Alterarea funciilor psihice - examen neurologic


obinuit normal, teste psihometrice alterate
- Manifestri neurologice absente
- EEG normal

_____________________________________

stadiul 1- Alterarea funciilor psihice - tulburri de somn,


modificri de personalitate, iritabilitate, depresie
- Manifestri neurologice - flapping tremor, deficit n
coordonarea micrilor, apraxie
- EEG - ncetinire simetric a ritmului

_____________________________________

_____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
78

_____________________________________

199

stadiul 2 - Alterarea funciilor psihice - somnolen,


dezorientare tulburri de comportament, calcul
matematic alterat, hipoprasexie
- Manifestri neurologice - flapping tremor, bradilalie,
ataxie, hiporeflexie osteotendinoas
- EEG - ncetinire simetric a ritmului + unde trifazice
lente frontal
stadiul 3 - Alterarea funciilor psihice - somnolen profund cu
reacie la stimuli, dezorientare, confuzie, amnezie,
operaiuni mentale imposibile
- Manifestri neurologice hiperreflexie
osteotendinoas, rigiditate muscular, Babinski
prezent
- EEG - unde trifazice lente generalizate

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

stadiul 4 - Alterarea funciilor psihice - com


- Manifestri neurologice Babinski prezent, pupile
dilatate, reflexe oculocefalice, decerebrare
- EEG - Ritm i foarte lent

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

80

_____________________________________

_____________________________________

Principalii factori precipitani n EHP

_____________________________________

Hemoragia digestiv superioar


Infeciile (de la pneumonii la PBS, etc)
Interveniile chirurgicale de la cele minim invazive la cele
complexe
Abuzul de diuretice, diselectrolitemii (alcaloza,
hipokalemia, etc)
Folosirea abuziv de sedative, tranchilizante, analgezice
Suprapunerea unei hepatite acute virale, alcoolice,
medicamentoase
Constipaia (crete absorbia i producia amoniacului)
Perturbri ale fluxului portal ( tromboz, unt
portosistemic transjugular)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

200

Diagnostic pozitiv : simptome neuropsihice la un pacient

_____________________________________

cunoscut cu ciroz hepatic

_____________________________________

Tabloul clinic asociaz:


1. Semne de insuficien hepatic:
- fetor hepatic (mercaptani)

_____________________________________
_____________________________________

cutanate ( icter , eritroz, buze carminate)

- stigmate de suferin hepatic: sindrom hemoragipar


sidrom ascito-edematos

2. Semne de HTP:
- circulaie colateral
- varice esofagiene
- ascit
3. Semne neurologice si psihiatrice:
- modificri de personalitate (bizar, iritabil, vulgar)
- modificari ale strii de constien
- modificarea intelectului: scderea capacitii de concentrare,
apraxie, modificarea scrisului
- neurologice: asterix sau flapping tremor

Investigaii paraclinice

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Umoral biochimic
afectare hepatic
- dozarea amoniemiei sanguine; hiperamoniemia pledeaz
pentru EHP, dar valorile normale nu o exclud; nivelul
amoniemiei nu se coreleaza cu gradul EHP
Modificrile EEG
- sunt extrem de rar folosite n practica curent i au specificitate
redus
CT( atrofie cerebrala difuz n etiologia alcoolic)
n cazuri selecionate:
RMN
Spectroscopia de rezonan (structura metabolismului
cerebral)
Tomografia cu emisie de pozitroni

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Diagnostic EHP minim

_____________________________________
_____________________________________
_____________________________________

Examen neurologic obinuit normal

_____________________________________

Alterarea testelor psihometrice (de la orientarea n timp


i spatiu pn la conexiuni numerice )

_____________________________________
_____________________________________
_____________________________________

Alterarea testelor neurofiziologice (poteniale evocate) i


nregistrarea modificrilor EEG determinate de stimuli
diveri (vizuali, auditivi, etc)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

201

_____________________________________
_____________________________________

Diagnostic diferenial (alte cauze care pot determina

_____________________________________

tulburri de contien)

_____________________________________

- encefalopatiile metabolice (coma uremic, diabetic,


tulburri hidroelectrolitice, acidobazice)
- come neurologice (accidente vasculare cerebrale,
tumori cerebrale)
- coma prin consum de alcool
- abuzul de sedative
- boli psihice

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
85

Principii de tratament

_____________________________________

_____________________________________
_____________________________________

1. Tratamentul afeciunii hepatice succesul este direct


proporional cu rezerva functional hepatic
2. Cunoaterea, identificarea i nlturarea factorilor
precipitani
3. Diminuarea produciei i absorbiei de amoniac i a altor
toxine la nivel intestinal (a, b, c, d)
a. Suport energetic 1800 - 2400 calorii/zi
- glucoz i hidrocarbonai
- administrare de vitamine i minerale
b. Restricie de proteine - iniial 40g/zi
- preferabil proteine din vegetale,
lapte (cu coninut sczut de
metionin, acizi aromatici)
- coninut crescut n fibre (determin
accelerarea tranzitului)
86

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c. Evacuarea colonului
- zaharuri neabsorbabile: lactuloza - dizaharid
neabsorbabil - inhib formarea de amoniac de ctre flora
intestinal cu creterea eliminrii fecale de azot
- 15-45 ml la 8-12 ore, per os
- clisma: 300 ml la1 l ap (la pacienii
aflai n com)
- clisma evacuatorie intestinal - n sngerrile
gastrointestinale

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202

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d. Modificarea florei intestinale


Antibiotice
Rifaximina - derivat neresorbabil al Rifampicinei, toleran
foarte bun, 1200 mg/zi (tableta are 200 mg), divizat in 3
prize
- acioneaz pe flora intestinal gram pozitiv i
negativ, aerobi si anaerobi
- superioar ca efect i tolerabilitate neomicinei,
vancomicinei i metronidazolului folosite anterior

_____________________________________

4. Metode chirurgicale:
- unturile chirurgicale nu se mai folosesc n prezent
- ideal transplant hepatic

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203

COMPLICAIILE CIROZEI
HEPATICE
HEPATOCARCINOMUL

89

Supravegherea pentru hepatocarcinom n


ciroza hepatic
- Screeningul pacienilor cu CH pentru depistarea n stadii
curative a HCC este foarte important
- Screeningul se face la 6 luni prin:
monitorizare combinat echografic
dozarea foetoprotein
- Regul! Orice nodul aprut pe fondul unei ciroze hepatice
este un potenial hepatocarcinom. n acest sens,
foetoproteina este semnificativ la valori peste 200 ng/ml

Atenie: 20 % din HCC nu sunt secretante i se nsoesc de


valori normale ale foetoproteinei

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Supravegherea pentru hepatocarcinom n


ciroza hepatic
Protocolul de urmrire a unui nodul hepatic este n funcie de
dimensiune:
1. noduli < 1 cm la echografia screening se urmresc la 3 - 6 luni;
dac nu cresc n urmtorii 2 ani se intr n programul normal de
urmrire a CH
2. nodulii de 1 - 2 cm la echografia screening necesit explorare prin
dou metode neinvazive dinamice (CT, RMN sau echografie cu
substan de contrast); dac aspectul este tipic (hipervascularizaie
n faza arterial, wash-out n cea venoas) se stabilete fr biopsie
diagnosticul de HCC. Nodulii fr aspect tipic necesit biopsie.
Dac rezultatul biopsiei nu este concludent se reduce perioada de
supraveghere la 3 6 luni. Dac nodulul crete se face o nou
biopsie
3. noduli > 2 cm cu aspect tipic la investigaia dinamic nu necesit
biopsie (n general foetoprotein > 200 ng/ml) diagnostic cert
de HCC

204

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Prognosticul CH

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Scor Child-Pugh

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Encefalopatie

Ascit

absent
stadiul 1-2
stadiul 3-4

1
2
3

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absent
minim( cu rspuns la diuretice)
refractar

1
2
3

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INR

Albumin (g/dL)

Bilirubina (mg/dL)

< 1.7
1.7-2.3
> 2.3

1
2
3

> 3.5
2.8-3.5
< 2.8

1
2
3

<2
2-3
>3

1
2
3

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Clasa A - scor 5-6


- supravieuire la 1 an - 100%

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Clasa B scor 7-9


- supravieuire la 1 an - 80%

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Clasa C scor 10-15


- supravieuire la 1 an 45%

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205

206

CANCERUL HEPATIC
PRIMITIV
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Epidemiologie

_____________________________________
a 3-a cauz de mortalitate prin cancer
consecina afeciunilor cronice hepatice (VHC, VHB, NASH, etc.)
distribuia HCC este neuniform:
- incidena corelat cu vrsta, sexul: Asia S-E i Africa > 20-28 x
comparativ cu Europa N, Australia i America de N
explicaiile posibile: vaccinarea hepatita B
condiiile de igien alimentar superioar
expunere redus la aflatoxine
accesul crescut la tratament

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- creterea HCC n zone cu risc mediu (Japonia,Europa de V)

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explicaii posibile: creterea duratei de viata n CH


tehnici imagistice performante

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Etiopatogenie

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Factori de risc major (cunoscui)

_____________________________________

Rasa, sexul masculin, vrsta > 50 de ani


asiatici x 2 > afro-americani i caucazieni
sex masculin/feminin: 3-4/1
explicaii: prevalena ridicata VHB, VHC alcool
vrsta ( interval liber de la infecia viral 20 - 30 ani HCC)
NB: nu este absolut necesar trecerea prin stadiul de CH
pentru HCC

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207

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Infecia cronic cu VHB

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- cea mai frecvent cauz de HCC n zonele cu prevalena


infeciei crescut
peste 2 miliarde de persoane pe glob au trecut prin
infecia B
din acestea 350 - 400 milioane au devenit purttori cronici
de virus B
riscul este mai mare dac infecia este veche sau dobndit
la natere ( 5-15 ori)
prevalena anual a HCC n infecia cronic VHB 0,5-2,5%

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Infecia cronic cu VHC

_____________________________________

- aproximativ 170-200 milioane de persoane infectate cu


virusul C
infecia cu virus C crete de 20 de ori riscul de HCC
coinfecia VHC + VHB ( 3-13%) crete de 3 -5 ori riscul
de HCC comparativ cu fiecare dintre infecii separat
genotipurile VHC ( 6 genotipuri - > 50 de subtipuri) - rol
diferit n carcinogenez

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Ciroza hepatic
indiferent de etiologie, este cel mai important factor de
risc pentru HCC (> 80% din cazuri)
carcinogeneza din CH este un proces multifactorial,
secvenial, multifocal n care displazia hepatocitar i
nodulii displazici sunt factori predictivi de risc pentru HCC

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Hemocromatoza ereditar

_____________________________________

risc > 20 ori pentru HCC + alte tipuri de cancer


comparativ cu populaia general
incidena HCC n hemocromatoza ereditar este de 5%
aproximativ jumtate din pacienii cu hemocromatoz
ereditar deces prin HCC

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6

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208

Alte afeciuni hepatice

_____________________________________

- steatohepatita non alcoolic nonviral


- hepatitele autoimune, boala Wilson, CBP riscul de HCC
este dificil de cuantificat

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Dieta aflatoxinele (contaminare Aspergillus flavus i

parasiticus)
- suprancarcare fier (recipiente de preparat/stocat Africa)
- algae blue green (heletee i lacuri) peptide
ciclice hepatotoxice China

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Factori de risc posibili

_____________________________________

Tutunul
Alcoolul
Contraceptive orale cu doze ridicate de hormoni steroizi

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7

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Tablou clinic

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HCC - complicaie frecvent n CH simptomatologia


proprie mascat de cea a bolii de baz ( one patient
two diseases)

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Principalele simptome de debut n HCC


1. agravarea brusc CH : febr, decompensare
parenchimatoas si/sau vascular
2. apariia (descoperit de pacient) unei formaiuni
superficiale n epigastru sau hipocondrul drept
3. prezena sindroamelor paraneoplazice:
poliglobulie (10% din pacieni) secreia tumoral de
eritropoietin
hipoglicemie (5% din pacieni) secreia de precursor
insulin- like
mai puin frecvente: hipercalcemie, sindrom carcinoid,
tromboflebit migratorie, etc.
4. pacient asimptomatic, descoperit la un examen de rutin

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Examenul clinic obiectiv

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Inspecia: de obicei pacient palid, icteric, caectic, febril,


circulaie colateral abdominal, ascit + alte stigmate de
suferin hepatic

Palparea: hepatomegalie neregulat, duritate lemnoas


uni sau bilobar
Splenomegalia atest suferina preexistent hepatic.
Palparea i percuia pot obiectiva ascita (semnul valului,
matitate deplasabil pe flancuri etc)

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209

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Explorarea paraclinic

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1. Explorarea funcional hepatic:

_____________________________________

- alterarea funciei hepatice cu modificarea celor 4 mari


sindroame (hepatocitoliz, colestaz, hepatopriv, reactivitate
mezenchimal)

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2.Tabloul hematologic este puin caracteristic, poate


evidenia anemie hipocrom sau din contra poliglobulie
(secreie de eritropoietin de ctre tumor), trombocitopenie
( atest suferina hepatic preexistent).

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3. Markeri tumorali:

_____________________________________

faetoproteina ( globulin) (AFP)


AFP: - valorile normale sub 10 ng/ml
- >200 ng/ml + imagini hepatice nodulare > 5 cm,
hipervascularizate Doppler - HCC (80%)
- 20 % din HCC sunt nesecretante de foetoprotein
- specificitate HCC : AFP L3 (lectina) > AFP

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Ali markeri tumorali: HCC incipient - glypican 3


HCC avansat - betacatenin
NB: Nu sunt folosii n practica curent.

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4. Examenul histopatologic

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Puncia biopsie hepatic (PBH) confirm HCC


Citologie prin aspiraie cu ac fin (FNAC) - mai puin invaziv,
diagnostic diferenial leziuni benigne/maligne (histopatolog
antrenat).
Tehnici de imunocito- i histochimie +microscopie
eletronic acuratee crescut n stabilirea diagnosticului

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210

5. Echografia standard Doppler cea mai folosit metod


neinvaziv
1. noduli solitari hipo, hiper sau izoechogeni
2. noduli multifocali
3. aspect difuz infiltrativ
Ecografia cu substan de contrast: umplere rapid n faza
arterial, wash out n faza parenchimatoas

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6. Computer tomografia (CT); cu substan de contrast este


extrem de util pentru confirmarea tumorilor hepatice mici i
stadializare n vederea deciziei terapeutice

_____________________________________

7. Rezonana magnetic nuclear (RMN) - detectare leziuni


mici - 95%.

_____________________________________

8. Tomografia cu emisie de pozitroni (PET) principiu:


evalueaza metabolismul aerob activ al glucozei la nivelul
celulelor maligne
- deceleaza diseminrile extrahepatice n HCC care nu au
putut fi vizualizate prin CT sau RMN.

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Diagnostic

_____________________________________

CH responsabil pentru 50 - 80% din HCC


leziune nedecelabil 4 -12 luni 2 cm
depistarea HCC n CH se face n dinamic prin monitorizare
ecografie
4 - 6 luni
dozare AFP
Ecografia - eficien crescut n diagnosticul i urmrirea
HCC la pacienii cu CH
specificitate de 93 % i sensibilitate de 71 %
regula: orice nodul hepatic suspiciune de HCC se
monitorizeaz

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Ecografie (consensuri)

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nodul sub 1 cm
>50% noduli hepatici < 1cm HCC
urmrire ecografic la 3 luni, cu dou posibiliti :
aceleai dimensiuni HCC
suspiciune HCC - monitorizare ecografica + AFP la 6
luni
nodul 1 cm i < 2 cm
biopsie ecoghidat cu ac fin + citologie i/sau examen
histopatologic
folosit nuanat n special n leziunile hepatice focale
cu diagnostic incert i n care tehnicile imagistice
performante nu au reuit s pun diagnosticul
noduli 2 cm
dac tehnicile imagistice stabilesc diagnosticul nu este
necesar biopsia
dozarea AFP - n general > 200 ng/mL

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211

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Diagnostic diferenial

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metastaze hepatice - cele mai frecvente sunt de la tract


digestiv, cancer primitiv pulmonar, sn, genito-urinar
cancer hepatic fibrolamelar prognostic mai bun, nu
asociaz factor etiologic cunoscut

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Complicaii

_____________________________________

insuficien hepatic
invazie vascular (tromboz de ven port)
extensie intrahepatic sau la distan
hemoperitoneu ( necroz tumoral)

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Stadializare obligatorie pentru decizia terapeutic


- stadializari numeroase (Okuda,CLIP ( Liver Italian Program), AJCC (American
Joint Cancer ), BCLC (Barcelona Liver Cancer)
- stadializarea Okuda - cea mai veche, imperfect - cea mai simpl
- folosete 4 variabile: albumina, bilirubina, ascita, mrimea tumorii
.

Factori
Dimensiuni
< 50% din ficat
Dimensiuni
> 50% din ficat
Ascit absent

Scor
supravieuire
0
1

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Stadiul I = 0 - supravieuire 8 luni


Stadiul II = 1-2 - supravieuire 1-3 luni
Stadiul III = 3-4 supravieuire 0,5-2 luni

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Ascit prezent

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Albumin seric
> 30 g/l
Albumin seric
< 30 g/l
Bilirubin
< 3 mg/dl
Bilirubin
> 3 mg/dl

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Tratament

_____________________________________

Prevenia primar:

_____________________________________

prevenirea hepatitei B i C;
vaccinarea pentru hepatita B;
expunere redus la aflatoxine;
interzicerea alcoolului, n special la persoanele infectate cu
virus B i /sau C
- tratamentul hepatitei cronice B sau C
- supravegherea cirozei hepatice, indiferent de etiologie

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19

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212

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Tratamentul chirurgical ideal i definitiv n HCC


este transplantul hepatic
supravieuirea la 5 ani este de 70 %
costul extrem de mare
numrul mare de cereri comparativ cu numrul redus de
donatori
frecvena n cretere a HCC
metod greu accesibil

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Chirurgia de rezecie este o alternativ fiabil atunci


cnd sunt ndeplinite criteriile de rezecabilitate

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- 10 - 30 % din cazuri

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curativ larg, dac nu asociaz CH


paleativ segmentectomii, enucleere - dac leziunea
este extins; recidiv tumoral crescut

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Metodele terapeutice ablative percutane (tumori


sub 4 cm):
chemoembolizarea
injectarea direct intratumoral de ageni chimici (alcool
absolut, acid acetic)
tehnici de distrucie tumoral mediate termic (laser,
microunde, ablaie prin radiofrecven)

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Ablaia prin radiofrecven, injectare de alcool absolut tehnici invazive percutane care au eficacitate similar
cu chirurgia de rezecie dac indicaia este riguros pstrat

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22

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213

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Chimioterapia sistemic

_____________________________________

rezultate puin promitoare n prezent; studii n


desfurare
cea regional (intraarterial hepatic) se poate
recomanda n cazuri selecionate

Terapii moleculare:
(HCC - hipervascularizat)

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Sorafenib (inhibitor oral multikinazic)


Avastin (bevacizumab)
TSU - 68 ( antiangiogenetic)

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Tehnica de tratament aleas depinde :


- de experiena i dotarea centrului de referin
- de stadiul n care este diagnosticat HCC

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214

PATOLOGIA BILIAR

COLECISTITA ACUT

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_____________________________________

Definiie: inflamaia acut a peretelui vezicii biliare


n peste 90% din cazuri complic litiaza biliar
vezicular

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_____________________________________

litiaza biliar vezicular este simptomatic numai n


15-20% din cazuri

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215

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Clasificare i etiologie:
Colecistita acut litiazic: n 90% din cazuri apare prin
suprainfecia litiazei biliare veziculare
Colecistita acut nelitiazic: factorul patogenic cel mai
important este ischemia
stri septicemice, oc chirurgical
posttraumatic (factori precipitani: respiraia
asistat, hipotensiunea, administrarea de opiacee)
postpartum ( factor precipitant: travaliul laborios)
vasculite (lupus eritematos diseminat, sindrom
Sjgren, periarterita nodoas)
parazitoze (foarte rar ascaris lumbricoides)
idiopatice sau primitive, fr cauz decelabil
evident

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Colecistita acut litiazic

_____________________________________

apare preponderent la sexul feminin, cu vrsta ntre 20-50


de ani
este consecina fenomenelor inflamatorii localizate la
nivelul veziculei biliare (peritonit localizat)
Tablou clinic
Durerea tipic mbrac aspectul de colic biliar
durere cu intensitate mare, sediul n hipocondrul drept
descris de bolnav variat: cramp, ruptur
adoptare de poziie antalgic (aplecat nainte)
iradiaz obinuit posterior (semicentur), ascendent
(omoplat) i regiunea interscapulovertebral
poate fi agravat de tuse sau micri brute
poate fi precipitat de abuzuri alimentare,
colecistokinetice
dureaz variabil i poate ceda spontan sau la
administrarea de antispastice
se poate nsoi de grea, vrsturi (alimentare, biliare),
jen n respiraie, meteorism abdominal, frisoane, febr

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Examenul obiectiv
Inspecie:
r subicter sclerotegumentar
stare general influenat
tahipnee, tahicardie
Palpare:
manevra Murphy pozitiv

_____________________________________

Explorri paraclinice
Biologice
VSH accelerat
leucocitoz cu neutrofilie
sindrom moderat de citoliz
sindrom de colestaz (bilirubin, fosfataz alcalin,
gamaglutamiltranspeptidaz crescute)

_____________________________________

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216

Explorare imagistic
Radiografia abdominal simpl: poate pune n eviden n
10% din cazuri calculi radioopaci
Echografia :
metoda de elecie pentru diagnostic
colecist cu perei ngroai > 3,5 mm
n interior imagini hiperechogene cu con de umbr
posterior
semnul Murphy echografic este pozitiv
Alte explorri:
scintigram hepatobiliar, tomografie computerizat
sau rezonan magnetic doar n cazuri selecionate
MRCP, ERCP, ecoendoscopie dac suspectm
litiaz coledocian asociat

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Diagnostic pozitiv
coexistena semnelor clinice (colica biliar i/sau
sindromul dispeptic biliar), biologice i imagistice
Diagnostic diferenial
ulcerul gastric sau duodenal n criz dureroas sau
ulcerul perforat
apendicita retrocecal
pneumonia bazal dreapt
pancreatita acut
infarctul de miocard
colica nefretic dreapt

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Evoluie. Complicaii
se poate nsoi de complicaii grave, care necesit
recunoatere i atitudine terapeutic adecvat

_____________________________________
_____________________________________
_____________________________________

Pancreatita acut
este complicaie evolutiv n colecistita acut
litiazic
poate coexista cu litiaza biliar vezicular
Hidropsul vezicular
complicaie frecvent n litiaza biliar
apare prin inclavarea unui calcul n infundibul sau
n canalul cistic
formaiune ovalar, mobil cu respiraia, elastic,
dureroas la palpare

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217

Piocolecistul i gangrena vezicular


complicaii grave n colecistita acut litiazic
alterarea sever a strii generale, febr septic,
contractur abdominal
necesit administrarea imediat de antibiotice cu
spectru larg n doze mari i intervenie chirurgical
Pneumocolecistul acut
complicaie rar, caracterizat prin prezena
aerului n colecist
factori favorizani :
obstrucia cisticului
calculii multipli
dac nu se intervine n urgen evolueaz ctre
necroz i coleperitoneu

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Litiaza coledocian
apare prin migrarea calculilor n coledoc cu
obstrucia temporar sau permanent a fluxului biliar
i apariia icterului (caractere clinice i biologice de
icter obstructiv)
ecografic: dilatarea cilor biliare intrahepatice i a
coledocului; calculul coledocian poate fi vizualizat
ecografic n 50% din cazuri
diagnosticul se precizeaz prin MRCP (metoda de
diagnostic preferat datorit caracterului noninvaziv), ERCP, ecoendoscopie
tratament: ERCP cu sfincterotomie i extracie de
calculi

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Perforaia
localizat
clinic se traduce prin plastron colecistic
poate abceda
abces subfrenic
n cavitatea peritoneal
determin coleperitoneul
semne clinice de iritaie peritoneal cu aprare
muscular, durere la tueul rectal, ileus paralitic
n lumenul digestiv
- fistul biliodigestiv (duoden, colon)

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218

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Tratament

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Medical
- repaus la pat
- interzicerea alimentaiei orale
- corectarea dezechilibrelor hidroelectrolitice (aprute
dup vrsturi i interzicerea alimentaiei orale)
- asigurarea unui debit urinar normal
- sond de aspiraie gastric
- administrarea de antibiotice (ampicilin, amoxicilin,
cefalosporine, ciprofloxacin, metronidazol)
Chirurgical de elecie colecistectomie laparoscopic
dup remiterea puseului acut

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Colecistita acut nelitiazic


mai frecvent la brbai, cu un raport B/F = 2/1
vrsta medie de apariie este peste 50 de ani
Factori favorizani:
- stri septicemice
- diabet zaharat
- pacieni n vrst, tarai sau cu multiple comorbiditi
Simptomatologia clinic
febra (25%)
+ durere n hipocondrul drept
Explorri paraclinice
Biochimice: VSH accelerat, leucocitoz

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Echografic: colecist destins, fr calculi, durere la


aplicarea transductorului (semn Murphy echografic),
grosimea peretelui vezicular > 3,5-4 mm, uneori
colecie lichidian pericolecistic (abces)
Complicaii
apar n special la persoane cu carene multiple, tarai
gangren
perforaie
Evoluie
poate evolua fatal n 10% din cazuri, la persoanele
tarate, cu multiple comorbiditi sau atunci cnd
diagnosticul a fost pus cu ntrziere
Tratament
n majoritatea cazurilor se recomand colecistectomie
de urgen

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219

SINDROMUL
POSTCOLECISTECTOMIE

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Totalitatea simptomelor i semnelor aprute la pacieni dup


colecistectomie
Prevalen: 20 40% din pacienii colecistectomizai
De obicei se datoreaz unor afeciuni concomitente: BRGE, ulcer,
pancreatit, sindrom de intestin iritabil etc, cel mai adesea existente
premergtor colecistectomiei
Mai frecvent la femei, n asociere cu tulburri psihice (depresie,
anxietate, insomnii)
Clinic simptomatologie polimorf: durere abdominal, greuri, vrsturi,
meteorism abdominal, saietate precoce, pirozis, tulburri de tranzit, rar
icter, episoade recurente de angiocolit
Explorri:
- biologic: normal sau sindrom de colestaz
- ecografic normal sau dilatarea cii biliare principale, bont cistic lung
- MRCP, ERCP, scintigrafie biliar, manometrie sfincter Oddi n cazuri
selecionate

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Manifestrile determinate de modificrile morfologice i


funcionale ale tractului biliar postcolecistectomie:

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Litiaza coledocian (poate fi rezidual sau recidivat;


tratament extracia calculilor prin ERCP)
Bontul cistic restant lung - > 5 mm (simptomatologie
asemntoare cu cea a colecistului, cu posibilitatea de
apariie a litiazei, tratament chirurgical)
Coledococelul (chist coledocian)
diagnostic i tratament
Stenozele biliare postoperatorii
prin ERCP
Stenoza Oddian
(sfincterotomie,
proteze biliare)
Disfunciile sfincterului Oddi

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220

TUMORI MALIGNE ALE


C
ILOR BILIARE

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Cancerul veziculei biliare i colangiocarcinomul sunt


entiti tumorale distincte care au n comun originea
embrionar i parte din factorii etiologici

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Prognosticul este rezervat

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Diagnosticul se face de obicei tardiv - prin lipsa


simptomatologiei n stadiile incipiente i a strategiilor
eficiente de screening

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221

CANCERUL DE VEZICUL

BILIAR

Date generale

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Inciden n cretere datorit mbtrnirii populaiei


Apare de obicei la 60-70 de ani
Preponderent la sexul feminin (2-3/1) probabil i datorit
incidenei crescute a litiazei biliare
Nu are inciden uniform pe glob:
- arii cu inciden crescut: Asia de sud est, nordul Indiei,
Pakistanul, Europa de est
- arii cu inciden sczut: SUA (nativii americani i
hispanicii au inciden uor mai mare)
Tipul histologic n peste 90% din cazuri este adenocarcinom
(90% schiros, 5% coloid, 5% papilar)
Este rapid metastazant (locoregional, limfatic sau sanguin)
datorit particularitilor anatomice ale colecistului (absena
muscularis mucosei i submucoasei)

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Factori de risc

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Litiaza biliar vezicular, simptomatic, cu calculi mari,


indiferent de compoziia lor (secvena probabil:
inflamaie-displazie-neoplazie)
Vezica de porelan (risc de 5%)
Polipii veziculari i adenomiomatoza vezicular entiti
cunoscute cu potenial malign
Anomaliile jonciunii pancreatico-biliare (efect iritativ al
sucului pancreatic n cile biliare, cu staz)
Expunere prelungit la factori de mediu toxici (industria
cauciucului, automobile, minier etc)

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222

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Tablou clinic

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Simptomatologie nespecific, adesea subevaluat,


mascat de cea a litiazei biliare cunoscute
Durere de tip colicativ biliar sau difuz abdominal, rebel
la tratament convenional
Sindrom dispeptic bilio-gazos trenant
Sindrom de impregnaie neoplazic (anorexie, inapeten,
scdere ponderal)
Examenul obiectiv poate evidenia, funcie de momentul
evolutiv:
- icter tegumentar
- hepatomegalie tumoral (prin invazie sau MTS)
- mas tumoral n hipocondrul drept
- ascit (carcinomatoz peritoneal)

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Diagnostic pozitiv

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Umoral-biochimic
- modificarea testelor de citoliz i colestaz
- markerii tumorali: CA19-9 i ACE crescui, dar nespecifici
Explorri imagistice
- Ecografia: sensibilitate de peste 80% - deceleaz mas
intravezicular (polipod de cele mai multe ori), cu ngroarea
peretelui vezicular (suferin veche) calculi invazie locoregional MTS hepatice, ganglionare i vasculare
- MRCP - superior CT n diagnostic i aprecierea extensiei
tumorale
- ERCP n prezent folosit numai terapeutic (plasare de
stent)
- EUS utilizat pentru confirmarea diagnosticului (examen
histopatologic) i stadializare

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Stadializare

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Stadiul 0 carcinom in situ


Stadiul I (T1N0M0) tumora invadeaz lamina propria (T1a) sau inelul
muscular (T1b)
Stadiul II (T2N0M0) tumora invadeaz esutul conjunctiv
perimuscular fr extensie subseroas sau n ficat (T2)
Stadiul IIIA (T3N0M0) tumora penetreaz seroasa (peritoneul
visceral) i/sau invadeaz direct ficatul i/sau alte organe adiacente
(stomac, duoden, colon, pancreas, ci biliare extrahepatice)(T3) fr
cointeresare ganglionar
Stadiul IIIB(T1-3N1M0) indiferent de extensia tumorii, afectarea
ganglionilor din hil precum i a celor de-a lungul cii biliare, arterei
hepatice, venei porte i canalului cistic (N1)
Stadiul IVA (T4N0M0) tumora invadeaz ramul principal al venei
porte sau arterei hepatice + 2 sau mai multe organe extrahepatice (T4),
fr cointeresare ganglionar
Stadiul IVB (orice T, orice N, M1 sau orice T,N2M0 sau T4N1M0 (orice
T cu metastaze la distan M1, orice T cu interesarea ganglionilor
celiaci, periduodenali, peripancreatici i/sau mezenterici superiori (N2)
sau T4N1M0

223

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Diagnostic diferenial

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Litiaza biliar vezicular


Tumorile benigne veziculare
Colangiocarcinomul
HCC

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Prognostic

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- Rezervat (tumor rapid metastazant cu simptomatologie

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necaracteristic)!

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Tratament

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Profilactic
- nu se recomand colecistectomie profilactic pentru
litiaza biliar vezicular asimptomatic (risc de cancer )
- colecistectomie: vezica de porelan, polipi > 1cm,
adenomiomatoz, litiaz simptomatic
Tratament chirurgical
- clasic dac diagnosticul este stabilit preoperator sau
prin convertirea laparoscopiei dac diagnosticul a fost
stabilit intraoperator
Radioterapie: extern, intraoperatorie sau brahiterapie,
indiferent de stadiul evolutiv, fr rezultate ncurajatoare
Chimioterapia adjuvant folosete 5 fluorouracilul i
mitomicina C, iar cea paliativ gemcitabina i ageni pe
baz de platinium

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224

CANCERUL CILOR BILIARE

Date generale

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25% din cancerele hepato-biliare


Inciden mai mic comparativ cu cancerul de vezicul biliar
Preponderen uoar pentru sexul masculin (1,3/1)
Vrsta medie de apariie 50 70 de ani
Histopatologic 95% din cazuri adenocarcinom
Clasificarea se face funcie de localizare:
- carcinom de cale biliar intrahepatic (colangiocarcinom
periferic)
- carcinom de confluen canal hepatic drept + stng (tumor
Klatskin cea mai frecvent)
- carcinom de cale biliar principal la distan de
confluen
Diseminarea - cel mai frecvent pe cale direct, n organele
din jur (ficat, port, arter hepatic, pancreas, duoden), dar i
limfatic, vascular, perineuronal

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Tablou clinic

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simptome clinice n general nespecifice


prurit (datorat icterului obstructiv)
durere abdominal necaracteristic, adesea singurul
simptom
semne de impregnare neoplazic (scdere ponderal,
anorexie, etc)

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Examenul obiectiv:
- icter leziuni de grataj
- hepatomegalie
- vezicul biliar palpabil n localizarea distal a
colangiocarcinomului

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225

Diagnostic pozitiv

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Umoral-biochimic
- sindrom de colestaz
- sindrom de citoliz (afectare hepatic prin colangit)
- markeri tumorali: CA19-9, ACE pot fi crescui fr a
avea specificitate pentru diagnostic
Imagistic
- Ecografia abdominal
- examen de prim intenie
- poate preciza localizarea tumorii, diseminarea
ganglionar i n alte organe
- CT este superioar ecografiei pentru stadializare
- RMN i MRCP - superioare CT, aduc un plus de precizie
n decizia terapeutic
- PET este folosit pentru detectarea tumorilor mici periferice
sau a MTS la distan pre- i postoperator

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Stadializare

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Stadiul 0: carcinom in situ


Stadiul I (T1N0M0) tumor limitat la peretele tractului biliar
Stadiul II (T2a sau 2bN0M0): tumora depete peretele
tractului biliar (T2a) sau invadeaz parenchimul hepatic (T2b)
Stadiul IIIA(T3N0M0): tumora invadeaz unilateral ramuri din
port sau artera hepatic (T3), fr interesare ganglionar
Stadiul IIIB(T1-3N1M0): T1-3 cu interesarea ganglionilor
regionali (N1)
Stadiul IVA (T4N0-1M0): tumora invadeaz trunchiul venei
porte, sau ambele ramuri, sau artera hepatic comun sau ci
biliare secundare bilateral sau unilateral cu invazie vascular
controlateral
Stadiul IVB: orice TN2M0 sau oriceToriceNM1: interesarea
ganglionilor la distan (N2): periaortici, pericavi, mezenterici
superiori, celiaci sau metastaze la distan (M1)

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Diagnostic diferenial

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Cancerul de cap de pancreas


Ampulomul Vaterian (icter ondulant, melen, anemie)
Cancerul de vezicul biliar stadii avansate
Hepatocarcinomul
Alte cauze de icter obstructiv (litiaz, parazitoze etc)

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Prognostic

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- rezervat
- n tumorile nerezecabile indiferent de localizare, media
de supravieuire este de 8 12 luni

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226

Tratament

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Chirurgical
- curativ cu extirpare tumoral, datorit extensiei este
rar posibil
- paliativ funcie de sediul tumorii (de obicei drenaj
biliar chirurgical anastomoz bilio-digestiv)
Endoscopic drenaj biliar endoscopic transtumoral,
proteze tumorale plasate endoscopic sau percutan
Radio i chimioterapia singure sau combinate reduc
recurena loco-regional
Transplantul hepatic nu se recomand; recidiv
tumoral n peste 50% din cazuri

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227

228

PANCREATITA ACUT
_____________________________________

Definiie: episod inflamator acut rezultat din


activarea intrapancreatic a enzimelor digestive

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Clasificare:
Pancreatita acut edematoas sau interstiial
80%
Inflamaie pancreatic moderat, autolimitant n
majoritatea cazurilor + edem interstiial +
refacerea funciei pancreatice dup remiterea
inflamaiei
Pancreatita necrotico-hemoragic 20%
Inflamaie + necroz de coagulare (pancreas,
esuturi adiacente) pancreatita necroticohemoragic

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Etiologie

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Cauze frecvente
- litiaza biliar

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75 85% din PA

- consumul de alcool
- hipertrigliceridemia
- ERCP
- traumatisme abdominale
- postoperator (intervenii chirurgicale abdominale i nonabdominale, transplant hepatic sau renal)
- medicamente (azatioprin, 6 mercaptopurin,
sulfonamide, estrogeni, tetraciclin, acid valproic,
medicamente anti HIV)
- disfuncia sfincterului Oddi

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229

Etiologie

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Cauze rare

_____________________________________

- ischemie (hipoperfuzie dup chirurgie cardiac)


- vasculite
- boli ale esutului conjunctiv
- purpur trombocitopenic trombotic
- cancer de pancreas
- hipercalcemie
- diverticul periampular, pancreas divisum, boal Crohn
duodenal, UD penetrant n pancreas
- pancreatit ereditar
- fibroz cistic
- insuficien renal
- infecii (citomegalovirus, coxsackie, parazitoze)
- boli autoimune (sindrom Sjogren)

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Fiziopatologie

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Faza enzimatic (de declanare) activarea


intrapancreatic a enzimelor digestive i lezarea celulelor
acinare

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Etapa rspunsului inflamator local (cascada rspunsului


inflamator)

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Etapa rspunsului inflamator sistemic (PAF, TNF, Il 6


etc) i a insuficienei multiple de organ

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Faza de restituie

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Fiziopatologie

_____________________________________

Ischemie, anoxie, infecii, traum, endo, exotoxine,


obstrucie

Activare tripsinogen n tripsin

Activare fosfolipaz A, elastaz, lipaz

Digestie membrane celulare, fibre elastice, vase

Edem interstiial, hemoragie, necroz parenchimatoas,


citosteatonecroz, vasodilataie

Eliberarea de citokine, histamin, substane vasoactive


rspuns inflamator sistemic

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230

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Extinderea procesului inflamator

Enzimele pancreatice activate distrug planurile


nvecinate i pot afecta: coledocul, duodenul, artera i
vena splenic, splina, spaiile pararenale, mezocolonul,
colonul, mezenterul, ganglionii celiaci i mezenterici,
omentul mic, mediastinul posterior i diafragmul
Afectare peritoneal ascit pancreatic
Afectare pleural pleurezie, pneumonie
Arsur chimic extravazare proteine din circulaia
sistemic n spaiile peritoneale i retroperitoneale
hipovolemie instabilitate cardiovascular, insuficien
respiratorie, renal

Evoluia PA este influenat de susceptibilitatea genetic


(mutaii n genele PRSS1m, SPINK1, CFTR, MCP1)

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Diagnostic clinic

_____________________________________
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Simptome :
Durerea abdominal
- localizat n epigastru, hipocondrul stng, periombilical,
cu iradiere posterioar, toracic, n flancuri i
abdomenul inferior
- caracter continuu, suprtor, exacerbat n decubit
dorsal, ameliorat n ortostatism i aplecat nainte

_____________________________________

Poate fi nsoit de grea, vrsturi, distensie abdominal


secundar ileusului

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Examenul fizic
- febr, tahicardie, hipotensiune pn la hipovolemie
- icter prin colelitiaz sau compresia coledocului
datorat edemului pancreatic
- semnul Cullen sau Turner (echimoze periombilical
sau pe flancuri)
- abdomen suplu
- matitate alternnd cu hipersonoritate la percuie
(tabl de ah)
- zgomote abdominale diminuate sau abolite (ileus)
- ascit, pleuerzie stng, pneumonie, focare de
citosteatonecroz, tetanie

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231

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Explorri biologice

_____________________________________

Amilaza seric (75% din pacieni) valori >3xN; apare


n primele 24 ore i persist 3-5 zile; se normalizeaz
dac nu exist necroz extensiv, obstrucie ductal
sau formare de pseudochisturi; nu exist corelaie
ntre valorile amilazelor i severitatea PA

_____________________________________

Lipaza seric crescut la 70% din pacieni

_____________________________________

Amilaza urinar poate rmne crescut pn la 7-10


zile dup normalizarea amilazei serice

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Leucocitoza - frecvent 10.000-20.000/ mmc

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Hemoconcentraie hematocrit > 50%

_____________________________________

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Hiperglicemie
Hipocalcemie la 25% din pacieni (fixarea calciului la
nivelul focarelor de steatonecroz)
Bilirubina, fosfataza alcalin, transaminazele pot fi
crescute, cu revenire la normal n 4-7 zile n absena
unei obstrucii coledociene
LDH (prognostic sever)
Hipoalbuminemie
CRP
Hipoxemie arterial la 25% din pacieni

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Cauze de creteri ale amilazelor


serice
Digestive
Pancreatit
Pseudochist pancreas
Abces pancreatic
Cancer de pancreas
Traumatisme pancreatice
Afeciuni biliare
(colecistit acut,
obstrucie coledocian)
Ulcer penetrant/perforat
Ocluzie intestinal
Ischemie/infarct intestinal
Ruptur de splin
Peritonit

Extradigestive
Sarcin extrauterin rupt
Anevrism/disecie aort
Insuficien renal
Cetoacidoz diabetic
Arsuri
Afeciuni ale glandelor
salivare
Cancer esofagian,
pulmonar, ovarian
Macroamilazemie

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232

Explorri imagistice
Rx pe gol excludere perforaie intestinal
- Semne nespecifice: ileus, ans santinel, semnul
colonului amputat
Echografia i CT
- Determinarea aspectului i mrimii pancreasului,
extensia inflamaiei i flegmonului, aspectul
tractului biliar, confirmarea colecistitei, colelitiazei,
pseudochisturilor, ascitei
- CT - diagnostic mai exact al necrozei pancreatice;
prezena aerului n parenchim sugereaz
suprainfecia; permite puncia ghidat

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Clasificarea Balthasar (CT)


A pancreas normal
B pancreas mrit de volum (segmentar, difuz),
hipodensitate heterogen, dilatare Wirsung, colecie
lichidian intraglandular
C B plus infiltraia grsimii peripancreatice
D C plus colecie lichidian unic la distan
E B plus peste 2 colecii la distan sau bule de gaz
pancreatice sau extrapancreatice
A, B evoluie favorabil

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Limitele CT n urgen:
- doar din PA evolueaz cu necroz
- prezena necrozei nu se coreleaz cu insuficienele de
organ
- necroza poate apare dup 24 48 ore

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ERCP n urgen: PA prin obstrucie biliar
- util dup stabilizarea pacientului n diagnosticul
etiologic (pancreas divisum, pancreas anular, cancer
pancreatic, anomalii ductale) i evidenierea comunicrii
ductului pancreatic cu pseudochisturile

Rezonana magnetic - avantaj fa de CT la pacienii


care necesit monitorizare dinamic (evit riscul iradierii
i al substanei de contrast)

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233

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Diagnostic pozitiv

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Cel puin 2 din 3 criterii:


Clinic (durere, greuri, vrsturi)
Biologic ( amilaze, lipaze > 3 x N)
Imagistic (CT, rezonan magnetic)

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Diagnostic diferenial

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Colecictita acut
Colic biliar coledocolitiaz
Perforaie intestinal
Ulcer peptic perforat
Ocluzie intestinal acut
Hepatit alcoolic
Hepatit viral

Ischemie/infarct mezenteric
Vasculite
Disecie, anevrism aort
Infarct miocardic

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Pneumonie
Colic renal
Apendicit acut
Cetoacidoz diabetic

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Criteriile Ranson n PA

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La internare

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Vrst > 55 ani


Leucocite > 16000/mmc (pacient nondiabetic)
Glicemie > 200 mg/dl
LDH seric > 350 UI/l
AST > 250 U/l

n primele 48 de ore
Vrst > 55 ani
Leucocite > 15000/mmc
Glicemie > 180 mg/dl (pacient nondiabetic)
Uree seric > 16 mmol/L
PaO2 < 60 mmHg
Ca seric < 8.0 mg/dl
Deficit baze > 4 mEq/L
Sechestrare fluide > 6 L
Albumina seric < 3,2 mg/dL
LDH > 600 U/L
ALT sau AST > 200 U/L

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Dificile, necesit
48 ore pentru
aprecierea
prognostic

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234

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Criterii de severitate (Atlanta)

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1. Complicaii locale (necroz, abces, pseudochist)


2. Insuficien de organ:
- oc: TAs < 90 mm Hg
- hipoxemie < 60 mm Hg
- insuficien renal: creatinin > 2 mg/dl
- HDS > 500 ml/24h
3. Scoruri iniiale de prognostic nefavorabil (Ranson,
APACHE)

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Complicaii
Locale

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Necroza (steril sau suprainfectat)


Colecii pancreatice (abcese, pseudochisturi se pot
complica cu ruptur, hemoragie, infecie, obstrucie
stomac, duoden, colon, tract biliar)
Ascita pancreatic
Necroza organelor nvecinate
Tromboz ven port, splenic
Infarct intestinal
Hemoragie intraperitoneal
Icter obstructiv

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Colecii pancreatice
Colecii lichidiene acute (conin suc pancreatic, nu au
perete, apar dup 48 h, rezoluie spontan > 50% din
cazuri)

Pseudochisturi (suc pancreatic i esut de granulaie, apar


dup 4 sptmni, rezoluie spontan n 80% din cazuri
dac sunt < 6 cm)

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Abcese (colecii purulente n vecintatea pancreasului,


apar dup 4 sptmni, diagnostic prin CT)

Necroz pancreatic (arii focale anecogene echografic,


asociate cu steatonecroz retroperitoneal; apar dup 48 h,
au mortalitate )
Necroz pancreatic suprainfectat (suprainfecia apare
la 36-71% din cei cu necroz; este polimicrobian; se
evideniaz dup 2-3 sptmni, diagnostic: puncie
aspiraie ghidat CT)

235

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Complicaii
Sistemice

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Pulmonare: pleurezie, atelectazie, abces mediastinal,


sindrom de detres respiratorie a adultului
Cardiovasculare: hipotensiune, hipovolemie, moarte
subit, modificri EKG: ST T, pericardit
Hematologice: coagulare intravascular diseminat
Renale: oligurie, retenie azotat, tromboz de
arter/ven renal, necroz tubular acut
Metabolice: hiperglicemie, hipertrigliceridemie,
hipocalcemie
Nervoase: encefalopatie, psihoz, embolii grsoase
Oculare: orbire brusc (retinopatia Purtschers)
Necroz grsoas (subcutanat eritem nodos, osoas)

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Tratament
La 85-90% din pacienii cu PA afeciunea este
autolimitant i se rezolv spontan; pacienii cu PA
sever sau cu factori de risc (vrstnici, obezi, valori
crescute ale Ht i ureei, pleurezie) necesit internare i
monitorizare n secii de terapie intensiv

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Repaus alimentar cu aspiraie nasogastric


reducerea secreiei pancreatice; introducerea treptat a
alimentaiei cu prnzuri mici bogate n carbohidrai dar
cu coninut redus n proteine i lipide
n PA sever se recomand nutriie enteral (tub nasojejunal), preferabil nutriiei parenterale totale

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Tratament

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Combaterea durerii: Meperidine (Demerol) 50-100 mg la 4-6


ore iv sau im este mai bine tolerat ca morfina. Morfina sulfat
n caz de durere sever
Somatostatina sau Octreotidul ar putea fi benefice prin
scderea secreiei enzimatice pancreatice (studii
contradictorii)
Hidratarea intravenoas (soluii coloide i cristaloide)
restabilete volumul intravascular, perfuzia pancreatic,
necroza
- 250 300 ml/h, cu Ht i ureei n primele 6 12 ore
(monitorizare pentru prevenirea suprancrcrii)
ERCP n primele 24 72 ore doar n caz de PA biliar prin
litiaz coledocian
Antibioticele nu se administreaz n scop profilactic numai
n necroz/colecii suprainfectate sau sepsis biliar

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236

Tratamentul necrozei pancreatice

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Identificarea necrozei (CT difereniaz coleciile lichidiene


de necroz)
Semnele clinice de necroz suprainfectat apar dup 10
14 zile
Puncie aspirativ cu ac fin ghidat CT, coloraie gram,
culturi, antibiogram:
- necroz steril: tratament suportiv, repetarea punciei la 57 zile dac starea clinic nu se amelioreaz
- necroz infectat: iniierea tratamentului antibiotic
(imipenem); dac pacientul este instabil drenajul
chirurgical imediat al necrozei; dac pacientul este stabil
se continu tratamentul antibiotic i se amn drenajul
necrozei care se va efectua ulterior dac mai este necesar
(chirurgical, endoscopic sau radiologic)

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Tratamentul pseudochistelor pancreatice

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Colecii lichidiene cu perete propriu, apar dup 2 3


sptmni de la episodul de PA
Clasic pseudochisturile > 6 cm necesit drenaj; n prezent
tratament conservator dac sunt asimptomatice
Trebuie drenate n caz de infecie (abces), durere,
compresiune (duoden, colon, coledoc)
Drenaj: tehnici endoscopice, radiologice, chirurgicale (n
funcie de localizare i experiena centrului)

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237

238

PANCREATITA CRONIC
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Definiie

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Boal inflamatorie cronic a pancreasului care evalueaz


cu fibroza i atrofia progresiv a parenchimului i
alterarea funciei pancreatice exo- i endocrine
Caracteristici:
distrugere progresiv i fibroz prin leziuni inflamatorii a
pancreasului
pierdere iniial a funciei exocrine i ulterior a celei
endocrine
complicat de pusee de acutizare responsabile de
recurena durerii
insuficien pancreatic cu malabsorbie, steatoree,
diabet zaharat

Clasificarea Marsillia Roma: calcificant (legat n


special de consumul de alcool), obstructiv, inflamatorie

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Etiologie-TIGAR-O

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Toxicmetabolic: alcool, fumat, hipercalcemie,


hiperlipemie, IRC, medicamente, toxine
Idiopatic: juvenil, senil, ereditar
Genetic:
autosomal dominant: gena tripsinogenului cationic
autosomal recesiv: mutatii CFTR, SPINK1
Autoimun: izolat sau n sindroame (Sjgren,BII,CBP)
PA Recurent: postnecrotic, afeciuni
vasculare/ischemice, postiradiere
Obstructiv: pancreas divisum, disfuncie sfincter Oddi,
tumori, chisturi periampulare

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239

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Morfopatologie

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Afectare lobular cu leziuni de intensitate diferit i


distribuie parcelar
Dopurile proteice ocup lumenul ductal sau acinar
calcificri, calculi
Atrofia epiteliului i stenoza ductelor pancreatice
Puseele recurente de PA chisturi de retenie,
pseudochisturi i inflamaie perineural

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Fiziopatologie

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1. Teoria stressului oxidativ: reflux biliar bogat n reactivi


oxidani
2. Teoria toxic metabolic: agresiune toxic direct
asupra celulelor acinare (de exemplu alcoolul)
3. Teoria obstructiv: creterea litogenicitii i obstrucia
ductelor pancreatice determinat de factori genetici i de
mediu
4. Teoria necroz fibroz: pusee repetitive de PA care
determin inflamaie, necroz i n final fibroz

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Fiziopatologie

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Celulele stelate pancreatice


- stimulate de citokinele inflamatorii (TNF, Il1, Il6),
factori oxidativi cresc sinteza de colagen
- au capacitatea de autoactivare autocrin prin TGF
ceea ce explic progresia bolii chiar dup ndeprtarea
factorului declanator

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Factorii genetici: mutaii n gena tripsinogenului cationic


(PRSS1), regulatorul conductanei transmembranare din
fibroza chistic (CFTR), inhibitorul proteazic serinic
(SPINK1)
- testele genetice de diagnostic nu au intrat n practica
curent n PC

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240

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Diagnostic clinic

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Aproximativ jumtate din pacieni prezint episoade


recurente de pancreatit acut

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1. Durere
2. Malabsorpie
3. Diabet zaharat

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1. Durerea

poate fi recurent sau continu


trenant, suprtoare, adesea intens,
cvasipermanent, nsoit de grea, cu sau fr
vrsturi
epigastric, periombilical, uneori n bar, cu
iradiere posterioar
se exacerbeaz postprandial, este accentuat de
clinostatism, ameliorat de poziia ortostatic i
aplecat nainte
necesit medicaie analgezic dependen
la majoritatea pacienilor durerea este constant n
primii 5 ani de la diagnostic; ulterior, la aproximativ
2/3 din pacieni, durerea dispare spontan sau scade
ca intensitate i frecven
10% din pacieni nu prezint durere

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2. Malabsorbia (diaree, steatoree, scdere ponderal)


a) Malabsorbia lipidelor i proteinelor
este manifest la pierderea a 90% din capacitatea
secretorie a pancreasului
malabsorbia proteic poate fi compensat prin
creterea aportului fr discomfort abdominal
adiional
creterea aportului lipidic agraveaz diareea i
durerea abdominal
b) Malabsorbia carbohidrailor
rar n pancreatita cronic
necesit pierderea a 97% din secreia de amilaz
c) Malabsorbia vitaminei B12
prin reducerea secreiei de tripsin cu rol n
clivarea complexului vitamin B12-proteina R i
eliberarea vitaminei B12 pentru cuplarea cu factorul
intrinsec

241

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3. Diabetul zaharat

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diminuarea secreiei de insulin i glucagon


70% din pacienii cu calcificri pancreatice fac DZ
complicaiile microangiopatice i nefropatice lipsesc
prin scderea secreiei de glucagon pacienii devin
sensibili la insulina exogen hipoglicemii la doze
mici de insulin

Examen fizic

mas palpabil (pseudochist)


scdere ponderal la pacienii cu malabsorbie
icter (obstrucie coledocian prin leziuni situate la
nivelul pancreasului cefalic)

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Diagnostic paraclinic

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1. Explorri biochimice

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- amilaza i lipaza pot fi normale chiar n timpul


episoadelor de pancreatit acut
- teste de funcionalitate hepatic modificat: boal
alcoolic concomitent sau obstrucie coledocian
- creterea glicemiei, hemoglobinei glicate
- valori moderat crescute ale CA19-9
- Ig G4, FR, ANA n pancreatita autoimun

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2. Explorri imagistice

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Rx abdominal poate evidenia calcificri panceratice la


1/3 din pacieni
Echografia
- ieftin, accesibil, non-invaziv, repetabil
- calcificri, pseudochisturi, dilataii ductale, tumori
- n 20% din cazuri dificil (esut adipos, gaz)
- criterii majore : Wirsung > 3 mm, chisturi > 10 mm,
calcificri
- criterii minore: modificri de contur, dimensiuni,
omogenitate

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242

Computer tomografia
- gold standardul metodelor imagistice non-invazive
- acuratee superioar comparativ cu ecografia n detectarea
calcificrilor, pseudochistelor, tromboza venei splenice, mas
pancreatic sau episod de PA
4 stadii:
- Normal: dimensiuni, form, omogenitate normal, Wirsung <
2 mm
- Echivoc/uor : 1-2 din : Wirsung 2-4 mm, hipertrofia glandei
(> 2ori), parenchim heterogen
- Moderat: chist < 10 mm, neregulariti ductale, pancreatit
focal, neregulariti de contur, creterea ecogenitii pereilor
ductali
- Sever :1 din criteriile precedente + : chist > 10 mm, defecte
de umplere intraductale, stenoze ductale, neregulariti severe
de contur, calcificri, interesarea organelor adiacente

ERCP cel mai sensibil i specific test pentru explorarea


morfologiei canalului pancreatic
- Wirsung neregulat cu dilatri i stenozri,
dilatarea i amputarea ductelor pancreatice secundare
- aspectul papilei lui Vater
- permite prelevarea de biopsii
- rol terapeutic (drenare pseudochist, litotripsie)
- risc de PA (se folosete doar n cazurile care
necesit tratament endoscopic)
Rezonana magnetic
- diferenierea PC de cancerul pancreatic
- colangiopancreatografia prin rezonan magnetic
(MRCP) a nlocuit practic ERCP ca metod de diagnostic

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Ultrasonografia endoscopic (EUS)


util dac suspectm prezena unei tumori pancreatice
- detecteaz precoce modificrile morfologice ale
parenchimului pancreatic i canalelor pancreatice
- asociat elastografiei crete acurateea diagnosticului
diferenial PC tumor pancreatic
Biopsia ghidat ecografie, EUS, CT
Alte metode
- Angiografia
- Scintigrafia: n prezent nlocuit de CT, RM
- Examen radiologic baritat gastro-duodenal: modificri
ale cadrului duodenal

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243

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3. Teste de insuficien pancreatic exocrin


Directe
Testul cu secretin
- gold standard
stimularea secreiei pancreatice cu secretin, sau
secretin-colecistokinin
la pacienii normali crete volumul secretor i secreia
de bicarbonat; n PC ambele sunt sczute
sensibilitate de 74-90%
Testul Lundh
dozarea enzimelor pancreatice n sucul pancreatic
obinut prin tubaj duodenal dup stimulare alimentar
sensibilitate de 60-90%

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Indirecte
Steatoreea: peste 10 g lipide n scaun la un consum de 100
g/zi; n insuficiena pancreatic avansat se poate ajunge la o
excreie de 40-50 g / zi
Elastaza 1 n materiile fecale
Testul la Bentiromid
- administrarea unui polipeptid ataat la PABA (acid
paraaminobenzoic); sub influena chemotripsinei peptidul se
desface de PABA, care se resoarbe i se elimin prin urin
- scderea eliminrii PABA semn indirect de suferin
pancreatic producie sczut de chemotripsin
- sensibilitate de 37-90%
Pancrealauryl test: se inger fluorescein dialaureat (va fi
clivat de estaraza pancreatic) i un prnz standard
Teste respiratorii cu trigliceride mixte sau triolein marcate cu
C13 (utile i n monitorizarea terapeutic a suplimentrii cu
fermeni pancreatici)

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Diagnostic diferenial

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Pancreatita acut pancreatit cronic acutizat


Pancreatita cronic cancer pancreatic (RMN, EUS,
puncie)
Durere: litiaz biliar, ulcer gastric sau duodenal,
ischemie mezenteric, cancer gastric, porfirie
Malabsorbie : enteropatie glutenic, boal Crohn
Complicaii: diagnostic diferenial ascit, pleurezie, icter,
HDS

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244

Complicaii
Locale
Pseudochisturi
pancreatice
Abcese
Stenoz coledocian
Obstrucie duodenal
Tromboz de ven port,
splenic
HDS (ulcer peptic,
pseudochist care
erodeaz duodenul,
efracie variceal prin
HTP segmentar)
Cancer pancreas
(risc de 10 x >)

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Sistemice
Secundare malabsorbiei
Ulcer gastric sau
duodenal
Serozite (ascit,
pleurezie, pericardit)
Necroze lipidice
metastatice
Necroze aseptice de cap
femural, humeral
Retinopatie non-diabetic
(deficit de vitamina A, Zn)

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Pancreatita autoimun
form de PC cu trsturi distincte clinice, serologice,
histologice i imagistice
Clasificare:
- tipul 1 afeciune sistemic (se asociaz cu
colangit, sialoadenit, fibroz retroperitoneal,
nefropatie, limfadenit)
- tipul 2 numai cu afectare pancreatic
2/3 din pacieni se prezint cu icter obstructiv sau mas
tumoral pancreatic
lipsesc atacurile recurente de PA
lrgirea pancreasului (sausage shape)
ngustare difuz, neregulat a canalului pancreatic +
anomalii ale ductelor biliare
absena calcificrilor sau chisturilor pancreatice

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Pancreatita autoimun

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Creterea imunoglobulinelor G4 (Ig G4)

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Prezena factorului reumatoid, ANA

_____________________________________

Histologic: infiltrat limfoplasmocitar i fibroz

_____________________________________
_____________________________________

Rspuns favorabil la corticoterapie (Prednison 40 mg/zi,


4 sptmni, cu scdere progresiv + imunomodulator
pe termen lung AZT, 6MP, micofenolat mofetil)

_____________________________________
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245

Criteriile HISORt PC autoimun

_____________________________________

Categorie

Criteriu

Histologie

Infiltrat limfoplasmocitar periductal cu tromboz


obliterant i fibroz la nivelul pancreasului
Infiltrat limfoplasmocitar cu celule IgG4 pozitive n
pancreas i alte organe afectate

_____________________________________

Tipic: mrirea difuz a pancreasului cu inel periferic (CT,


RMN); neregularitate difuz a canalului pancreatic
(MRCP, ERCP)

_____________________________________

Serologie

Ig G4

_____________________________________

Afectarea
altor organe

Stricturi biliare intrahepatice sau la nivelul coledocului


distal, afectarea glandelor parotide/lacrimale, adenopatii
mediastinale, fibroz retroperitoneal

_____________________________________

Rspuns la
corticoterapie

Rezoluia/ameliorarea manifestrilor
pancreatice/extrapancreatice la corticoterapie

_____________________________________

Imagistic

_____________________________________

_____________________________________
_____________________________________

_____________________________________

_____________________________________

_____________________________________
_____________________________________

_____________________________________

Tratament

_____________________________________
_____________________________________
_____________________________________

Tratamentul:
A. Durererii
B. Malabsorbiei
C. Diabetului zaharat

_____________________________________
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_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

A. Tratamentul durerii

_____________________________________
_____________________________________

Mecanismele durerii: inflamaia acut, creterea presiunii


intrapancreatice, inflamaia neural

_____________________________________
_____________________________________

Opiuni terapeutice:
- analgetice
- ntreruperea consumului de alcool
- inflamaiei
- presiunii intrapancreatice ( secreiei, ndeprtarea
obstruciei)
- modificarea transmiterii neurale

_____________________________________
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_____________________________________
_____________________________________
_____________________________________
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246

Analgetice
-iniial non-narcotice, ulterior narcotice (Tramadol, Morfin)
-dependen!

_____________________________________

ntreruperea consumului de alcool diminu frecvena


episoadelor dureroase, a calcificrilor i complicaiilor

_____________________________________

Scderea inflamaiei:
- ntreruperea fumatului
- ntreruperea alimentaiei per os, nutriie enteral sau
parenteral total
- antioxidani, inhibitori de radicali liberi de oxigen
- chirurgie n pancreatita obstructiv
- prednison n pancreatita autoimun

_____________________________________
_____________________________________

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Scderea secreiei pancreatice: reducerea aciditii


gastrice, suplimentarea cu enzime pancreatice,
sandostatin
Scderea presiunii intrapancreatice
a. Decompresia canalului pancreatic
- drenajul pseudochistelor (percutan, endoscopic,
chirurgical) (eficacitate )
- decompresia canalului pancreatic dilatat: stent sau
litotripsie (eficacitate )
b. Proceduri chirurgicale: rezecie parial,
pancreatojejunostomie longitudinal sau caudal,
pancreatectomie total cu autotransplant de celule istmice
Modificarea neurotransmiterii:
- Amitriptilin - scade percepia durerii
- blocarea plexului celiac cu xilin i alcool (ghidat
ecoendoscopic sau CT) sau splahnicectomie
toracoscopic
- stimulare magnetic transcranial

B. Tratamentul malabsorbiei
-

pentru o steatoree pn la 10 g lipide/zi este suficient


restricia aportului lipidic
n cazul unei steatorei peste 10 g/zi se recomand
suplimentarea dietei cu enzime pancreatice i restricia
aportului lipidic
Supliment enzimatic
- sunt necesare aproximativ 30.000 IU lipaz / prnz
- administrare nainte de mas: Creon, Zymogen,
Triferment, Mezym etc
- efecte adverse: grea, crampe abdominale, excoriaii
perianale, hiperuricemie, litiaz renal, reacii alergice
- lipaza este inactivat la un pH sub 4.0 se vor
asocia IPP sau anti H2 sau se vor administra
preparate enzimatice cu nveli enteric

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_____________________________________

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247

_____________________________________

Suport nutriional
- przuri mici i dese, bogate n proteine
- trigliceride cu lan mediu (MCTs) 40 g/zi
- nutriie parenteral dac cea enteral nu este
tolerat

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

C. Tratamentul DZ
-

monitorizare atent a administrrii de insulin


(risc de hipoglicemie) !!

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
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248

CANCERUL PANCREATIC
_____________________________________
_____________________________________

Date generale

_____________________________________
_____________________________________

Neoplazie extrem de agresiv, putin sensibil la


chimioterapie complex, cu supravieuire la 5 ani sub 4 %
Agresivitatea extrem face posibil urmtoarea afirmaie:
supravieuirea, incidena i mortalitatea pot fi considerate
identice
Fr tratament, n medie, supravieuirea este de luni, iar
la 1 an sub 5 %
Simptomatologia iniial necaracteristic, de tip dispeptic
trenant, determin ca numai 15- 20 % din pacienii fr
metastaze la distan, s beneficieze de cur chirurgical

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Factori de risc

_____________________________________

Demografici

_____________________________________

- vrsta naintat > 75 ani

_____________________________________

- sexul masulin: uor preponderent 1,3 1,5 /1


- originea etnic: frecven mai ridicat la negri, nativi din
Noua Zeeland

_____________________________________
_____________________________________
_____________________________________

Genetici

_____________________________________

- predispoziie genetic: - 8-10 % din pacienii


diagnosticai cu CP sub 40 de ani au rude de gradul I
sau II cu CP
- istoricul familial de CP - crete riscul de CP de > 50 ori

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

249

_____________________________________

Factori de mediu i modul de viata (cresc riscul


de CP de 2 20 de ori)
- fumatul: riscul de CP este proporional cu numrul de igri
fumate
- consumul redus de fructe i legume, crescut n grsimi,
obiceiuri culinare ( prajit, grtar) sunt factori favorizani
pentru CP
- alcoolul, cafeaua, AINS - rezultate neconcordante i
neconcludente

_____________________________________
_____________________________________
_____________________________________
_____________________________________
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_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Condiii medicale

_____________________________________

Pancreatita cronic ereditar preponderent CP


apare la marii fumtori, dup 70 de ani

_____________________________________
_____________________________________

Diabetul zaharat este consecin i nu factor favorizant


al CP

_____________________________________
_____________________________________
_____________________________________

Obezitatea se coreleaz cu risc crescut de CP

_____________________________________
_____________________________________

Alte conditii
cancerul colorectal nonpolipozic
- sindromul Peutz Jeugherz
- ataxia telangiectazia

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Screening n CP

_____________________________________

Rezultate i argumente cost/eficien insuficiente

_____________________________________

Societatea American de Gastroenterologie sugereaz


nceperea screeningului la vrsta de 35 de ani la cei cu
pancreatit ereditar i la 25 de ani la persoanele care au CP
familial
Screeningul se face prin:
- metode noninvazive: analiza mutaiei genelor n snge
i materii fecale, CT spiralat, PET, rezonan magnetic
nuclear.
- metode invazive: echoendoscopie, pancreatoscopie,
ERCP cu citologie abraziv i analiza sucului biliar, duodenal,
pancreatic pentru mutaii genice (Kras, P53)

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250

Tablou clinic

_____________________________________

Durerea: - prezent n peste 90% din CP


- n special n localizrile la nivelul corpului i cozii
- exacerbat de alimentaie, hiperextensia dorsal
- ameliorat de ingestia de acid acetilsalicilic

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Icterul cu caracter obstructiv apare n 70% din CP, n special n


localizrile cefalice metastaze hepatice

_____________________________________
_____________________________________

Scderea ponderal este ntotdeauna prezent i evolueaz


rapid spre caexie

_____________________________________
_____________________________________

Intolerana la glucoz este prezent n aproximativ 80% din


CP

_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Alte simptome din CP: depresia, labilitatea emoional,


vrsturile postalimentare, tromboflebita superficial migratorie
(fr etiologie sau factor favorizant), hemoragia digestiv
superioar (extensia splenic cu HTP segmentar sau direct
prin erodarea duodenului)

_____________________________________
_____________________________________
_____________________________________
_____________________________________

Examenul obiectiv:
- caexie
- icter tegumentar ( obstructie sau metastaze)
- leziuni de grataj adesea suprainfectate
- n localizrile la nivelui cozii tromboflebita migratorie recidivant
- hepatomegalie
- vezica biliar destins, nedureroas, palpabil (semn Courvoisier
Terrier)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Forme clinico topografice n CP

_____________________________________

Cancer de cap de pancreas

_____________________________________

- icter progresiv + prurit


- scdere n greutate
- hepatomegalie
- semnul Courvoisier- Terrier
dureri de intensitate redus

_____________________________________
_____________________________________
_____________________________________

Cancer de corp de pancreas


- durere intens (exacerbat imediat postprandial)

_____________________________________

- scdere ponderal
- icter ( mai puin frecvent)

_____________________________________

Cancer de coad de pancreas

_____________________________________

- durere intens
- tromboflebit migratorie
- tulburri de glicoreglare
- atenie absena icterului!

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251

Stadializarea CP

_____________________________________

Tis - carcinom in situ


T1 - tumor limitat la pancreas 2cm
T2 - tumor limitat la pancreas > 2cm
T3 - tumor extins direct n duoden, ci biliare, esutul
peripancreatic
T4 - tumor extins direct n stomac, splin, colon, vase mari
adiacente
N0 - fr metastaze ganglionare regionale
N1 - cu metastaze ganglionare regionale
M0 - fr metastaze la distan
M1 - metastaze la distan
Stadiul I
T1-T2
N0
M0
II
T3
N0
M0
III
T1-T3
N1
M0
IVA
T4
orice N M0
IVB orice T orice N
M1

_____________________________________

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_____________________________________

Investigaii de laborator

_____________________________________
_____________________________________

Umoral - biochimic: nVSH, n glicemie, sindrom de


colestaz ( FA, GGTP, bilirubina)

_____________________________________
_____________________________________

Markerii tumorali: CA 19-9 crescut n 80 % din cazuri

_____________________________________
_____________________________________

Markerii moleculari: oncogenul K ras se gsete n 90%


din CP . Apare n toate formele evolutive de CP, se poate
determina relativ uor n aspiratul duodenal, materii fecale sau
bil

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Investigaii imagistice

_____________________________________
-

Ultrasonografia: examen de prim intenie, argumentnd


icterul obstructiv i locul obstruciei (ci biliare intrahepatice
dilatate). Permite puncia echoghidat i un bilan relativ
corect al cointeresrii celorlalte organe (n special ficat)

- Computer tomografia: aduce un plus de calitate imaginii.


Prin CT diagnosticul, bilanul extensiei tumorale i
posibilitatea de rezecie se cuantific corect n 90 % din
cazuri

- Echoendoscopia: informaii n plus:


n tumorile mici, izodense comparativ cu pancreasul invazie
vascular portal sau splenic
permite biopsia preoperatorie

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252

Rezonana magnetic nu ofer avantaje comparativ cu CT

_____________________________________
_____________________________________

Colangiopancreatografia retrograd endoscopic _____________________________________


are sensibilitate mare (95%) identic cu MRCP. Limitele MRCP:
- nu poate preciza invazia, stadiului tumoral, sau preleva
material pentru examen histopatologic

_____________________________________
_____________________________________
_____________________________________

PET (positron emission tomography)

- difereniaz CP de pancreatita cronic


- comparativ cu CT are sensibilitate mai mare n diagnosticul
metastazelor limfatice
- se folosete electiv n suspiciunea de recurene postrezecie
pancreatic

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Diagnostic diferenial

_____________________________________

Afeciuni benigne: pancreatita cronic, icterul


extrahepatic, calculi n calea biliar principal, stenoze ale
cilor biliare (postchirurgicale, colangita sclerozant),
colecistita acut, penetrarea pancreatic a unui ulcer
gastric sau duodenal

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Afeciuni maligne: limfomul retroperitoneal,


cancerul cilor biliare, ampulomul vaterian, cancerul de
duoden sau intestin subire

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tratament

_____________________________________

Tratament chirurgical

_____________________________________

cu viz curativ
Duodenopancreatectomia
- intervenie cu mortalitate ridicat 25%
- supravieuirea este sub 1 an (medie 11 luni)

_____________________________________

cu viz paleativ
- coledocojejunostomie
- mortalitate operatorie 20%
- supravieuire maxim 5 luni

_____________________________________

_____________________________________
_____________________________________
_____________________________________

_____________________________________
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253

_____________________________________
_____________________________________
_____________________________________

Radioterapia extern dup cura chirurgical i chimioterapie


(5 fluorouracil) - crete durata supravieuirii dar nu i calitatea
vieii

_____________________________________
_____________________________________
_____________________________________

Chimioterapia fr cur chirurgical, n cazurile avansate de


boal, nu crete media supravieuirii comparativ cu pacienii
tratai simptomatic, fie c se folosete un singur citostatic (5
fluorouracil) sau combinaie cu antibiotice antitumorale
(mitomicina C, streptozocina)

_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________

Tratamentul simptomatic paleativ


Durere: - antalgice (paracetamol i antiinflamatorii nonsteroidiene,
codein, tramadol, morfin, fentanyl transdermic)
- antidepresive triciclice controleaz durerea neurogen
continu sub form de arsur
- anticonvulsivante - controleaz durerea fulgurant
- neuroliza plexului celiac
- splachnicectomia
Icterul: stent prin colangiopancreatografie retrogad endoscopic,
colangiografie percutan
anastomoz biliodigestiv
Obstrucia duodenal gastroenteroanastomoz
- jejunostomie percutan
- nutriie parenteral
Scderea n greutate - nutriie parenteral
Depresia - antidepresive i suport psihiatric

_____________________________________
_____________________________________
_____________________________________
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254

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