CRISTINA CTLINA

CIJEVSCHI PRELIPCEAN 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 EHP: encefalopatie hepato-portal

neted
ERCP: colangiopancreatografie retrograd
AST: aspartataminotransferaza 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
Introducere
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 gastro-
esofagian, colon iritabil): What matters in chronic
disorders is the patients suffering, not the disease entity
ENDOSCOPIA DIGESTIV SUPERIOAR
Primul endoscop optic flexibil a fost realizat de Hirschowitz
i colaboratorii
Este metod diagnostic i terapeutic
ERCP colangiopancreatografie endoscopic retrograd
EUS ultrasonografie endoscopic
n ultimii ani progrese n acurateea diagnosticului prin
cromoendoscopie, magnificaie, narrow band imaging
1
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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
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)
! Consimmnt informat
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
dilatare stenoze: esofagiene, pilorice
extragere corpi strini
proteze
polipectomii
mucosectomie endoscopic
tratament endoscopic n BRGE, acalazia cardiei
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
sedarea cu midazolam reacii alergice, hipotensiune,
depresie respiratorie
Endoscopia digestiv inferioar
Indicaii:
sngerare digestiv (rectoragie sau sngerare ocult)
boal inflamatorie intestinal
suspiciune de polipi, cancer
durere abdominal cu etiologie neprecizat
tulburri de tranzit intestinal
Contraindicaii:
aceleai ca la endoscopie +
boal inflamatorie intestinal fulminant
megacolon toxic
3
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Pregtire:
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- Evacuarea colonului (fortrans, picoprep, clisme
evacuatorii) _____________________________________
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Posibilitate de efectuare cu sedare _____________________________________
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Endoscopia digestiv inferioar terapeutic:
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polipectomii
mucosectomie _____________________________________
tratament hemostatic (injectare de substane _____________________________________
vasoconstrictoare, fotocoagulare, clipuri etc) _____________________________________
dilatare stenoze
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stenturi
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Complicaii _____________________________________
Complicaii majore _____________________________________
Perforaia _____________________________________
Hemoragia
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< 1% din colonoscopii, mai frecvent n cele terapeutice
(polipectomii) _____________________________________
Alte complicaii _____________________________________
Aritmii cardiace _____________________________________
Reacii vasovagale
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Hipotensiune, insuficien cardiac (pregtire
colonoscopie) _____________________________________
Reacii la medicamentele folosite pentru sedare _____________________________________
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Colangiopancreatografia endoscopic
retrograd - ERCP
- Vizualizarea cilor biliare i canalului pancreatic
- Invaziv (risc de pancreatit acut!) n scop diagnostic
metoda a fost nlocuit de tehnici noninvazive (MRCP)
- i pstreaz valoarea i utilitatea ca metod terapeutic:
- sfincterotomie endoscopic extracie de calculi
- stentare endoscopic
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4

Enteroscopia
Vizualizarea intestinului subire
Rol diagnostic (inclusiv prelevare de biopsie) i terapeutic
(hemostaz, polipectomii)
Eficien diagnostic comparabil cu videocapsula
Tehnici: spiral, dublu balon etc
Metod laborioas, necesit sedare, dotare i endoscopist
cu experien
CAPSULA ENDOSCOPIC
1966, Fantastic Voyage (Raquel Welch) submarin
miniaturizat aruncat n circulaia sanguin
Ideal o singur capsul pentru explorarea complet a
tractului digestiv, de la cavitatea oral la anus
n prezent capsul IS, esofag, colon
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
5
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Indicaii
- boala Crohn
- hemoragia gastrointestinal de cauz obscur
Indicaii relative
- boala celiac
- suspiciunea unei tumori maligne de intestin subire
- polipoza intestinal ereditar (sindromul Peutz-
Jeghers, 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)
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)
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
Ideal n suspiciunea de stenoz sau alte leziuni
obstructive se administraz capsula de paten
biodegradabil!
6
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Concluzii
capsula endoscopic s-a impus ca cea mai performant
metod de examinare a intestinului subire
reprezint metoda de elecie n diagnosticul bolii Crohn
i pentru stabilirea etiologiei hemoragiei digestive de
cauz obscur
este metod sigur, practic lipsit de complicaii dac se
face selecia adecvat a pacienilor
dezavantajele sunt legate de pre, imposibilitatea de a
preleva biopsii i de a efectua manevre terapeutice
Viitor capsul ideal?
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.
EXAMENUL RADIOLOGIC
Radiografia abdominal simpl: perforaie, ocluzie,
calcificri
Radiografia baritat eso-gastro-duodenal
Tranzit intestin subire
- specificitate, sensibilitate reduse
- enteroclisma
Clisma baritat (irigografia)
Colecistografia oral sau intravenoas nlocuite
de tehnici mai performante
7
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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)
Computer tomografia
Rezoluie superioar ecografiei
Difereniaz formaiunile solide de cele chistice
Permite puncia cu ac fin (diagnostic), drenarea chisturilor
suprainfectate, abceselor (terapeutic)
Rezonana magnetic
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
Tomografia cu emisie de pozitroni
Are avantajul evalurii nu doar structurale, ci i funcionale;
rol n detectarea recidivelor neoplazice la distan
Puncia biopsie hepatic
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
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
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%)
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
cele mai multe studii au fost efectuate la pacieni cu hepatit
cronic viral C
includ:
- elastografia n timp real HiRTE sau ARFI
- elastografia tranzitorie Fibroscan-ul
- elastografia prin rezonan magnetic
Elastografia n timp real
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)
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
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
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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
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 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)
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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
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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
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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
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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
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 _____________________________________
Diagnostic pozitiv ( 1- 4)
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Anamneza esenial n afirmarea diagnosticului
Important de urmrit urmtoarele etape _____________________________________
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1) simptomele de alarm
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- scderea ponderal necesit imediat investigaii
- vrsturile incoercibile invazive pentru excluderea: _____________________________________
- HDS (hematemez, melen) - leziunilor organice
_____________________________________
- sindromul anemic - altor afeciuni (DZ,
afeciuni tiroidiene, cardiace) _____________________________________
- disfagia afectare tiroidian, afeciune _____________________________________
- icterul
+ _____________________________________
- examen baritat cu _____________________________________
suspiciuni de diagnostic
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- mas abdominal
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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)
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Diagnostic diferenial _____________________________________
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1) refluxul gastro- esofagian (arsuri retrosternale,
regurgitaii acide) _____________________________________
important de difereniat ntruct are terapie diferit _____________________________________
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2) colonul iritabil
- asociaz n 50 % din cazuri simptomatologie _____________________________________
dispeptic _____________________________________
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3) toate afeciunile organice care se nsoesc de sindrom
dispeptic _____________________________________
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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
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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
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 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
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 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.
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Testarea Helicobacter pylori _____________________________________
Teste invazive: _____________________________________
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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 _____________________________________
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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
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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
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 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
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Terapia standard de eradicare pentru Hp _____________________________________

Maastricht IV 10-14 zile _____________________________________
_____________________________________
IPP CLARITROMICINA METRONIDAZOL AMOXICILINA
_____________________________________
1. IPP 500mg x 2/zi 1000 mg x 2/zi
_____________________________________
2. IPP 500mg 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 _____________________________________
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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
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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
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Terapia de linia a II-a n eradicarea HP _____________________________________

(10-14 zile ) _____________________________________
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IPP n doze standard Bismut Tetraciclin Metronidazol
_____________________________________
Omeprazol 20 mg x 2/zi Subcitrat de _____________________________________
Lansoprazol 30 mg x 2/zi bismut 120
mg x 4/zi _____________________________________
Pantoprazol 40 mg x 2/zi 500 mg x 3/zi 500 mg x 3/zi
Rabeprazol 20 mg x 2/zi sau _____________________________________
Esomeprazol 20 mg x 2/zi Amoxicilin
1g x 2 / zi
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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
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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 93% _____________________________________
Claritromicin 500 mg x 2/zi 94% _____________________________________
_____________________________________
Fr efecte secundare
_____________________________________
Terapia secvenial - eradicare semnificativ mai mare _____________________________________
comparativ cu terapia convenional 10 zile.
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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
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 BOALA DE REFLUX
GASTROESOFAGIAN
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Definiie: totalitatea simptomelor i modificrilor histo- _____________________________________
patologice 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
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_____________________________________
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)
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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 gastro-
duodenale 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
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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
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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
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 _____________________________________
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VI. BILITECH
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aprecierea refluxului alcalin
procedeu asemntor pH-metriei _____________________________________
colecistectomizati, stomac operat _____________________________________
_____________________________________
VII. Impedana esofagian _____________________________________
diferenierea refluxului funcie de consisten (solid,
lichid etc) _____________________________________
_____________________________________
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_____________________________________
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
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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
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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
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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
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 _____________________________________
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 _____________________________________
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Medicaia prokinetic
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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)
_____________________________________
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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
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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 non-
absorbabile la nivelul jonciunii pentru ngustarea lumenului
(lipsa de standardizare)
Complicaii - n general uoare
- rar, complicaii severe: pneumonii de aspiraie,
mediastinit i hemoragie digestiv superioar
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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
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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
- Absena peristalticii
- Peristaltic hipotensiv
(intermitent, frecvent)
- Peristaltic hipertensiv
- Esofagul sprgtor de nuci
- Spasmul esofagian
(segmentar sau difuz)
Cu afectarea relaxrii
jonciunii eso-gastrice
- Acalazia cardiei (clasic, cu
compresiune esofagian,
spastic)
- Obstrucia funcional a
jonciunii eso-gastrice
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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
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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
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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)
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42
 _____________________________________
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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 _____________________________________
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_____________________________________
Examen obiectiv - normal _____________________________________
Probe biologice - nemodificate _____________________________________
_____________________________________

Diagnostic paraclinic _____________________________________

EDS _____________________________________

Manometria _____________________________________

Examenul radiologic _____________________________________

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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)
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de
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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
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 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
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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)
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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 _____________________________________
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45
 _____________________________________
Tratament _____________________________________
_____________________________________
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MEDICAL
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ENDOSCOPIC _____________________________________
CHIRURGICAL
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_____________________________________
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
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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 printr- _____________________________________
un tunel submucos creat prin abord endoscopic la nivelul
mucoasei esofagiene _____________________________________
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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
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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
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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)
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Cancer esofagian _____________________________________
1. Adenocarcinom _____________________________________
2. Scuamos _____________________________________
_____________________________________

Factori de risc _____________________________________

Adenocarcinom _____________________________________
- BRGE, esofagul Barrett ( displazia sever, esofag _____________________________________
Barett segment lung), hernia hiatal voluminoas _____________________________________

- obezitatea _____________________________________
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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, ulcero-
vegetant, infiltrant: stenoz asimetric
Confirmare diagnostic - histopatologie din biopsia
prelevat din leziune
50
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 _____________________________________

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 _____________________________________
_____________________________________
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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
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Evoluie, prognostic _____________________________________
_____________________________________
Evoluie rapid, invazie local, metastaze locale sau
_____________________________________
regionale
_____________________________________
Supravieuire la 1 an sub 75% n absena tratamentului _____________________________________
_____________________________________
Tratament _____________________________________
Chirurgical _____________________________________
Endoscopic _____________________________________
Radioterapie
_____________________________________
Chimioterapie
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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-plasma-
cu 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
52
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 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
_____________________________________

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%
_____________________________________
_____________________________________

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 %
3. 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
_____________________________________
4. Alimentatia _____________________________________
- anumite alimente pot favoriza dispepsia dar nu exist
relaie direct diet ulcer, inclusiv pentru alcool i cafea _____________________________________

53
 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
7. Factorul genetic
- Rudele de grd I ale pacienilor cu UD risc de 3 x >
Rol HP?
- grupul sanguin O(I) , nesecretor - risc 1,5 x >
_____________________________________
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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
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
_____________________________________
_____________________________________
_____________________________________
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_____________________________________

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
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54
 Morfopatologie
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
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
Diagnostic
Anamnez: simptomatologie, antecedente heredo-
colaterale, fumat, AINS, afeciuni asociate
Evidenierea infeciei Hp: metode invazive/non-invazive
EDS
Examen radiologic baritat
55
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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 _____________________________________
_____________________________________
Nia - 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
_____________________________________
_____________________________________

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
 _____________________________________
_____________________________________
_____________________________________
Dispepsia de tip ulceros
- simptome identice _____________________________________
- diagnostic - endoscopic - absena leziunilor ulceroase _____________________________________
_____________________________________
Esofagita de reflux
- formele cu pirozis _____________________________________
- accentuarea simptomelor n clinostatism _____________________________________
- cedarea rapid la antiacide
_____________________________________
- endoscopie - prezena esofagitei
- absena ulcerului _____________________________________
_____________________________________
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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_____________________________________
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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
_____________________________________
_____________________________________
_____________________________________
_____________________________________

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? _____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
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)
_____________________________________
_____________________________________
_____________________________________

_____________________________________
Evaluarea preendoscopic _____________________________________
_____________________________________

Accesul la 1 sau 2 linii de abord venos _____________________________________

Obligatoriu: hemoleucogram, uree, electrolii, teste
funcionale hepatice, grup sanguin, Rh, timp de
protrombin
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
Aspiratul nasogastric orientativ
rousngerare activ - 30%
za de cafeasngerare recent - 3%
clar 50% sngerare intermitent, duodenal
11% sngerare sever
nu evideniaz sursa sngerrii
Semnificaia EDS n urgen
Endoscopia urgent (precoce, imediat): primele 24 ore
de la prezentarea n serviciul de urgen
Putere discriminatorie
Endoscopia n urgen + tratament endoscopic:
resngerarea
chirurgia n urgen
mortalitatea
Evaluarea severitii HDS
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
Scorul Blatchford non endoscopic: uree, hemoglobin,
tensiune arterial sistolic, puls, melen, hematemez, sincopa,
suferina hepatic i cardiac
59
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 Evaluarea endoscopic _____________________________________
(recurena i prognosticul Forrest, Laine, Peterson)
_____________________________________

Clasificarea Tipul de leziune Frecvena _____________________________________

Forrest resngerrii _____________________________________
IA Sngerare n jet, pulsatil, 55%-90% _____________________________________
arterial
_____________________________________
IB Prelingere continu, 55%-90%
nepulsatil a sngelui dintr- _____________________________________
o leziune _____________________________________
IIA Vase vizibile nesngernde 40%-55%
_____________________________________
IIB Cheag aderent 10%-33%
_____________________________________
IIC Baza de culoare neagr a 7%-10%
leziunii _____________________________________
III Fr stigmate de sngerare 3%-5% _____________________________________
_____________________________________

_____________________________________
_____________________________________
Tratamentul HDS _____________________________________
_____________________________________
Medicamentos _____________________________________
Endoscopic _____________________________________
Chirurgical
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

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
_____________________________________
Inhibare rapid i Meninerea constant _____________________________________
complet a pompei a concentraiei IPP n _____________________________________
de protoni snge, pH>6
_____________________________________
+ dup 72 ore IPP po +/- tratament Hp
_____________________________________
Momentul iniierii: naintea EDS _____________________________________
_____________________________________

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)
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
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
_____________________________________
_____________________________________
_____________________________________
_____________________________________

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 _____________________________________
_____________________________________
_____________________________________

_____________________________________
_____________________________________
Examene de laborator
- VSH _____________________________________
- leucocitoz _____________________________________
- penetraie - pancreas - amilaze serice i urinare
_____________________________________
- ci biliare bilirubinei
- hepatic - transaminazelor _____________________________________
_____________________________________
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

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
Tratament medicamentos, endoscopic (dilatare), chirurgical
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_____________________________________
PRINCIPII DE TRATAMENT
_____________________________________
N ULCERUL PEPTIC NECOMPLICAT
_____________________________________
_____________________________________
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 _____________________________________
_____________________________________

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)
_____________________________________
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_____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

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 _____________________________________
_____________________________________
_____________________________________
_____________________________________
_____________________________________

_____________________________________
Medicamente folosite n tratamentul
ulcerului peptic _____________________________________
_____________________________________

Inhibitori ai aciditii
Antiacide
Antagoniti receptori H2
Inhibitori pomp de protoni
Protectori ai mucoasei
Sucralfat
Prostaglandine
Preparate de bismut
Dicarbocalm, Maalox, Malucol,
Rennie, Epicogel, Almagel, Ulcerotrat
Cimetidina, Ranitidina, Famotidina,
Nizatidina
Omeprazol, Lansoprazol, Rabeprazol,
Pantoprazol, Esomeprazol,
Dexlansoprazol
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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
Antisecretoriile
1. Antagonitii receptorilor histaminici H2
acioneaz competitiv cu histamina endogen blocnd
secreia de HCl
comparativ, frecvena vindecrii este similar la doze
echivalente pentru aceste medicamente
IPP sunt superiori blocanilor H2!
65
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 _____________________________________
Antagonitii H2 _____________________________________
_____________________________________
Medicament Doz Observaii
_____________________________________
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 Nu interfer cu _____________________________________

2/zi metabolismul
citocromului P450
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Efecte secundare ale antagonitilor H2: _____________________________________

_____________________________________
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)
_____________________________________
_____________________________________
_____________________________________

2. Inhibitorii pompei de protoni (IPP)
Aciune principal - blocarea la nivelul celulei parietale a
pompei responsabile de secreia de HCl (H+/K+-ATPaza)
_____________________________________
_____________________________________
_____________________________________
_____________________________________

Primul descoperit : omeprazolul, urmat de lansoprazol, _____________________________________

rabeprazol, pantoprazol, esomeprazol, dexlansoprazol
Inhibiia pompei de protoni este maxim dac se administreaz
nainte de mas
Inhibiia secreiei gastrice acide este de 24 de ore
Poteneaz efectul bactericid pe Hp al antibioticelor probabil
prin meninerea unui pH alcalin intragastric
_____________________________________
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66

Inhibitorii pompei de protoni
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)
IPP i tratamentul anticoagulant (Clopidrogrel)
- metabolism competitiv la nivelul citocromului P450
- Clopidogrelul riscul ulcerului peptic (n special n asociere
cu aspirina), IPP eficacitatea Clopidrogrelului (Plavix)
- 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
- noi antiagregante (tienopiridine de generatia a- III-a
cu efecte secundare < asupra tractului digestiv)
Inhibitorii pompei de protoni
Omeprazolul 40 mg /zi
Lansoprazolul 30 mg/zi
Pantoprazolul 40 mg/zi
Esomeprazolul 40 mg/zi
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
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
67
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Protectorii mucoasei gastrice
Preparate de bismut coloidal
Sucralfatul
Prostaglandinele
Preparate cu bismut coloidal
DeNol - tablet de 120 mg subcitrat de bistmut coloidal
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
Important! folosit singur nu vindec ulcerul peptic
Sucralfatul
Acioneaz prin stimularea citoproteciei endogene,
mulndu-se pe craterul ulceros
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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Sucralfatul
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
Prostaglandinele
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
Efecte secundare: diaree, metroragii, contracii uterine
Forme clinice de ulcere i atitudinea
terapeutic
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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 Forme clinice de ulcere i atitudinea
terapeutic
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
Numrul interveniilor chirurgicale a sczut ca urmare a
eradicrii Hp i a tratamentului (IPP, tratament
endoscopic n complicaii)
Chirurgie laparoscopic sau clasic
Indicaii:
- electiv: ulcerul refractar
- n urgen: HDS, perforaia, insuficiena
evacuatorie gastric
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Complicaii postoperatorii _____________________________________
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Ulcerul recurent
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Sindromul de ans aferent
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Sindromul Dumping
Diareea postvagotomie _____________________________________
Gastropatia de reflux biliar _____________________________________
Maldigestia, malabsorbia _____________________________________
Cancerul de bont gastric _____________________________________
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70
 CANCERUL GASTRIC
Date generale
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)
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
n Europa - locul 3 la decese dup cancerul pulmonar i
colorectal
brbai:femei 2:1
vrsta de diagnostic: 65-75 de ani cu o medie de 70 de
ani la brbai i 74 de ani la femei
distribuie: 39% stomacul proximal, 17% treimea medie,
32% antrumul i 12% ntreg stomacul
71
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 _____________________________________
Factori de risc i afeciuni cu risc
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crescut n CG
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1. Infecia cu H. pylori
2. Dieta _____________________________________
3. Leziunile precanceroase _____________________________________
anemia Biermer _____________________________________
gastrita atrofic cu metaplazie intestinal _____________________________________
polipii gastrici adenomatoi
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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
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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
1) Cancerul gastric precoce (tumor limitat la mucoas
i submucoas, fr metastaze ganglionare loco-
regionale)
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
2) Cancerul gastric avansat
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
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
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 Stadializare
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
Tablou clinic
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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- 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)
Examen obiectiv
inspecie
tegumente palide sau icterice la un pacient
emaciat, cu facies suferind
semne de iritaie meningeal (n metastazele
meningeale)
formaiune care bombeaz n epigastru
palpare
formaiune palpabil epigastric
hepatomegalie tumoral (metastaze hepatice)
ascit (carcinomatoz peritoneal)
splenomegalie (HTP segmentar)
prezena adenopatiilor supraclaviculare stngi
sau axilare
Diagnostic paraclinic
I) 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
II) 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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 III. Examenul endoscopic
- cea mai bun metod de diagnostic att pentru CG
precoce ct i pentru cel avansat
- 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%
- cromoendoscopia, endoscopia cu magnificaie, narrow
band imaging - cresc acurateea diagnosticului n CG
precoce
IV. Examenul radiologic
tipul vegetant : imagini lacunare sau defecte de
umplere care determin ntreruperea continuitii
peretelui gastric
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
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
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)
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
EDS cu examen histopatologic al biopsiei prelevate
precizeaz diagnosticul
Bilanul extensiei: radiografie toracic, echografie
abdominal standard, echoendoscopie i/sau CT
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
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
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rezecie gastric - supravieuire la 5 ani:
90% n stadiul I _____________________________________
50% n stadiul II _____________________________________
10% n stadiul III
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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
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
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)
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)
Tratamentul suportiv
Nutriia: jejunostom, tub naso-gastric sau naso-jejunal,
gastrostom percutan endoscopic, nutriie parenteral
Tratamentul durerii
Obstrucie: tratament endoscopic (stent sau laser)
Iradiere paliativ (pentru durere, sngerare, metastaze
osoase)
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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)
Tablou clinic
Simptome puin specifice: durere epigastric (90% din
cazuri), scdere ponderal, grea, vrsturi, anemie _____________________________________
Examenul clinic obiectiv
- la debut - poate fi normal.
- tardiv n evoluia bolii :
- inspecia - paloare
- palpare - mas tumoral epigastric
- adenopatii
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
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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
Limfoamele cu grad redus de malignitate
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
Limfoamele MALT gastrice cu grad nalt de
malignitate
- diseminri sistemice n momentul diagnosticului
- 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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84
 PATOLOGIA
INTESTINULUI SUBIRE
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
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
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oculte, anemie)
Tulburrile de tranzit (diaree, constipaie) _____________________________________
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Examen obiectiv _____________________________________
General
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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)
Tueul rectal
durerea fundului de sac Douglas (peritonita)
identificarea unor mase tumorale abdominale
absena materiilor fecale n ampula rectal (ocluzii)
snge (ischemie intestinal)
Examene paraclinice
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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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
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)
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)
87
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 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
Principii de tratament
Tratament etiologic: pentru fiecare cauz de sindrom de
malabsorbie n parte
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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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
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.
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
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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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
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
Afeciuni asociate n boala celiac
Demonstrate statistic: diabet zaharat tip 1, deficit
selectiv Ig A, dermatit herpetiform, ciroz biliar
primitiv
Posibil asociate: tiroidit autoimun, epilepsie cu
calcificri cerebrale, nefropatie mezangial cu Ig A,
poliartrit reumatoid, boal Addison,sarcoidoz
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 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 anti-
transglutaminaz tisular i antigliandin - specificitate i
sensibilitate crescut pentru diagnostic
Complicaii
Afeciuni maligne ale tractului digestiv (limfom malign
non-Hodgkin, adenocarcinom)
Jejunoileita ulcerativ
Boal celiac colagenic
Tulburri endocrine, neuropsihice, leziuni osoase
Tratament
Diet fr gluten
rspuns clinic favorabil n 3-6 sptmni
rspuns morfopatologic cu restitutio ad integrum n 3-
5 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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TUMORILE INTESTINULUI
SUBIRE
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)
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
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 - n stadiile
finale evolutive
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 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)
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
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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 _____________________________________
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Explorarea umoral-biochimic
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- anemie hipocrom feripriv; teste pozitive pentru hemoragii
oculte _____________________________________
- sindrom de colestaz (n cazul tumorilor periampulare) _____________________________________
- teste hepatice modificate (metastaze) _____________________________________
- teste de malabsorbie
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- tumori carcinoide: dozarea serotoninei i a metabolitului urinar
5 - hidroxi indolacetic _____________________________________
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Forme clinice _____________________________________
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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
_____________________________________
_____________________________________

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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- 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)
Tratament
Tratamentul chirurgical
- curativ sau paliativ
- enterectomie segmentar cu rezecie mezenteric pentru
limfadenectomie
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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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
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acoperite cu mucus
diaree matinal sau la stress _____________________________________
emisie de mucus fr snge _____________________________________
dureri abdominale: frecvent cu caracter de discomfort _____________________________________
abdominal
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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.
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
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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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 _____________________________________

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Prezena semnelor clinice de alarm impun explorri
suplimentare i exclud diagnosticul funcional: _____________________________________
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Vrsta peste 50 de ani
Anemia _____________________________________
Anorexia _____________________________________
Febra
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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:
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- afeciuni inflamatorii (RCUH, BC)
- neoplazii _____________________________________
- infecii (colita pseudomembranoas, infeciile parazitare, _____________________________________
bacteriene)
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99
 _____________________________________
Tratament
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Afeciune funcional cronic
- 2/3 pacieni - afectare psihiatric (depresie i/sau _____________________________________
anxietate) _____________________________________
- dieta - rol important
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- medicaia folosit temporar
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- alteori tratament de lung durat
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Relaia de ncredere medic pacient primordial!
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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
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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 _____________________________________
_____________________________________
Dieta trebuie s fie variat, echilibrat n principii alimentare _____________________________________
i adaptat formei clinice.
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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
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
Dieta n forma cu predominana balonrii
y De evitat :- alimente care produc multe gaze (banane, prune,
varz, ceap, elin, fasole)
Dieta dac se asociaz deficit lactazic diet fr lapte sau
derivate din lapte
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!
101
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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
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)
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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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
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
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
Atenie: risc de colit ischemic!
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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 ulcero-
hemoragic (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.
RECTOCOLITA ULCERO-
HEMORAGIC
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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 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
Etiologie
Factori genetici (agregare familial)
Dieta: alergia la proteinele din laptele de vac, consumul de
dulciuri rafinate, alptarea insuficient la sn, prelucrarea
termic excesiv etc
Factori infecioi: E. coli
Consumul de contraceptive orale
Fumatul, ca i apendicectomia au rol protectiv
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
106
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Tablou clinic
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
II. Manifestri extradigestive
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
Diagnostic de laborator
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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 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
Clisma baritat
- util n formele cronice, pentru evaluarea extinderii leziunilor
- aspect granular al mucoasei, tergerea haustrelor (edem)
- spiculi marginali, aspect de buton de cma (ulceraii)
- pseudopolipi (imagini lacunare)
- ileit de reflux (backwash ileitis)
- forme cronice - haustre disprute, calibru diminuat,
distensibilitate redus, aspect de microcolie
Forme clinice
Evolutive
- acut fulminant
- cronic intermitent
- cronic continu (mai rar)
Extensie: - proctite (46%; 50% evolueaz progresiv)
- colite stngi (17%)
- pancolite (37%)
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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
Forme clinice - severitate
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
Diagnostic pozitiv
Clinic
Colonoscopie
RCUH Radiologie
Ex. histopatologic
Laborator
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Diagnostic diferenial
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Colitele infecioase (Shigella, Entamoeba histolitica, Campylobacter,
Giardia, Esherichia coli, Criptosporidium, Mycobacterium avium, _____________________________________
Citomegalovirus, Histoplasma, Treponema pallidum,Herpes simplex,
Chlamydia trachomatis) _____________________________________
Colita pseudomembranoas (Clostridium) _____________________________________
BC
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Hemoroizii i fisurile anale
Cancerul colo-rectal _____________________________________
Polipii colo-rectali _____________________________________
Diverticuloza colonic _____________________________________
Colita ischemic (rect indemn!)
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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 _____________________________________

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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
Factorii precipitani: hipokaliemia, utilizarea anticolinergicelor
i opiaceelor, explorrile endoscopice
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Examenul obiectiv evideniaz abdomen destins, meteorizat, _____________________________________

sensibil la palpare, cu dispariia zgomotelor hidro-aerice _____________________________________
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Megacolonul toxic _____________________________________
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Radiografia abdominal simpl arat dilatarea
colonului transvers > 6 cm _____________________________________
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Explorarea colonoscopic sau irigografic sunt _____________________________________
contraindicate!
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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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Clase de medicamente
Aminosalicilaii
Corticosteroizii
Agenii imunomodulatori
Terapia biologic (anti TNF)
Alte clase de medicamente: antibiotice, probiotice
Aminosalicilaii
Preparate de acid 5-aminosalicilic (5-ASA)
n tratamentul de inducie n formele uoare i moderate
n tratamentul de ntreinere al RCUH
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)
Aminosalicilaii
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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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
nu pot fi folosii n meninerea remisiunii
Agenii imunomodulatori
sunt folosii n tratamentul de ntreinere, n formele
cortico-dependente, cortico-rezistente sau n cazul
pacienilor care au contraindicaii pentru corticosteroizi
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
Terapia biologic
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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Alte clase de medicamente
Antibioticele sunt utile doar n cazul complicaiilor
(megacolon toxic). Nu i-au dovedit eficacitatea n
tratamentul de rutin al puseelor de RCUH
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
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
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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
Se practic proctocolectomie total cu ileo-anastomoz i
crearea unui rezervor ileal (pouch)
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)
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
afecteaz egal ambele sexe (cu uoar predominen la sexul
feminin)
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
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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 non-
steroidiene, statusul socio-economic ridicat
Fiziopatologie
fiziopatologia BC este asemntoare RCUH
predomin rspunsul imun de tip Th1 (celular, reacii de
hipersensibilitate ntrziat)
se elibereaz citokine inflamatorii: IFN, Il2, Il12, Il18, cu
creterea produciei de TNF i NF-B
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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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
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
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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 Explorri biologice
x 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
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
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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 _____________________________________
Ecografia _____________________________________
- ngroarea peretelui intestinal _____________________________________
- zone de stenoz sau dilatare
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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 A1: < 17 ani _____________________________________
diagnosticului A2 >17 - 40 ani
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A3: > 40 ani
Localizare L1: ileal _____________________________________
L2 :colonic _____________________________________
L3: ileocolonic
L4: tract digestiv superior (se _____________________________________
adaug L1-L3 cnd afectrile _____________________________________
coexist)
Forma clinico-evolutiv B1 nonstenozant, nonpenetrant _____________________________________
(fenotip) B2 stenozant _____________________________________
B3 penetrant
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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
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- 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
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Abcese _____________________________________
Fistule _____________________________________
Stenoze _____________________________________
Manifestri perianale
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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
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)
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
121
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Agenii imunomodulatori
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
Derivaii 5-ASA
eficacitate limitat n BC
pot fi folosii n formele uoare sau medii de BC cu afectare
colonic
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)
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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 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 non-
melanozice, 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
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)
123
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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
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Dup 50 ani riscul crete exponenial (mutaii genetice
succesive acumulate) _____________________________________
_____________________________________
_____________________________________

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
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)
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
Polipoza adenomatoas familial (FAP)
boal autosomal dominant, mutaii gena APC sau gena
MYH (20%)
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
126
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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
Polipoza adenomatoas familial atenuat: prezena <
100 de adenoame, apare cu 10 ani ntrziere fa de
FAP, polipi localizai cel mai frecvent n colonul proximal
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
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
Responsabil pentru 20% din CCR
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
Dup 8 ani supraveghere colonoscopic
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
128
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 Factorii de mediu _____________________________________
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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 _____________________________________
_____________________________________

_____________________________________
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 _____________________________________
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3 5% sincrone sau metacrone
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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
 _____________________________________
Stadializarea CCR _____________________________________
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Clasificarea Dukes
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Clasificarea TNM
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- Invazia tumoral
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- Afectarea ganglionar
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- 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 _____________________________________
Stadiul C1: 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
_____________________________________
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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 ileo- _____________________________________
colice,colic stng,medie,dreapt, mezenterica inferioar i rectala
superioar _____________________________________
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130
 _____________________________________
Stadiul TMN Dukes Supra- _____________________________________
vieuirea
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la 5 ani
Std 0 Tis No Mo - >95% _____________________________________

Std II T1/T2 No Mo A 80-95% _____________________________________

Std IIA T3 No Mo A 72-75% _____________________________________

Std IIB T4 No Mo B 65-66% _____________________________________

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Std IIIA T1/T2 N1 Mo B 55-60%
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Std IIIB T3/T4 N1 Mo C 35-42%
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Std IIIC Oricare T N2 Mo C 25-27%
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Std IV Oricare T Oricare N M1 C 0-7%
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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!
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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)
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 Diagnostic diferenial _____________________________________
_____________________________________
Hemoroizi, fisuri anale _____________________________________
BII _____________________________________
Diverticuloza colonic
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Colita ischemic i colita radic
Angiodisplazia colonic _____________________________________
Colonul iritabil _____________________________________
Tuberculoza intestinal _____________________________________
Endometrioza intestinal _____________________________________
Limfomul intestinal
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Alte cancere digestive
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Evoluie. Prognostic _____________________________________
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evoluie lent progresiv
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pacieni cu CCR recidivant - supravieuire < 5 ani de la
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diagnostic
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pacieni cu metastaze hepatice - supravieuire 4,5 luni
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diagnostic precoce i chirurgie n stadiile curabile -
supravieuire la 5 ani 80% _____________________________________
_____________________________________

Complicaii: metastazarea, ocluzia, perforaia, _____________________________________

hemoragia _____________________________________
_____________________________________
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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 ileo-
anal/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
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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
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 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)
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 Recomandri de screening i _____________________________________

supraveghere _____________________________________
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Risc mediu (populaie asimptomatic > 50 de ani) _____________________________________
- Hemoragii oculte anual _____________________________________
- Sigmoidoscopie sau clism baritat cu dublu contrast
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sau colonoscopie virtual la 5 ani
- colonoscopie la 10 ani _____________________________________
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Recomandri de screening i supraveghere _____________________________________

Risc crescut (1) _____________________________________
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Categorie de Metod
risc _____________________________________
Istoric 1-2 adenoame < 1 cm Colonoscopie la 5 _____________________________________
personal 10 ani _____________________________________
de polip
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3 10 polipi sau polip > Colonoscopie la 3
1 cm sau polip vilos sau ani _____________________________________
displazie nalt _____________________________________
> 10 polipi Colonoscopie la < 3
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ani
Polip sesil (polipectomie Colonoscopie la 3 _____________________________________
piecemeal) 6 luni _____________________________________
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Recomandri de screening i supraveghere _____________________________________

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Risc crescut (2) _____________________________________
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Istoric perioperator Colonoscopie _____________________________________
personal de nainte de operaie
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CCR sau n primele 6 luni
dup _____________________________________
postoperator Colonoscopie la 1, _____________________________________
3, 5 ani de la
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explorarea
anterioar _____________________________________
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Recomandri de screening i supraveghere _____________________________________
_____________________________________
Risc crescut (3) _____________________________________

Istoric 1 rud grd I < 60 ani sau Colonoscopie la 5 _____________________________________

familial de 2 rude de grd I cu CCR ani ncepnd de la _____________________________________
polipi sau 40 de ani sau cu 10
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CCR ani mai devreme
dect vrsta _____________________________________
diagnosticului rudei _____________________________________
cu CCR
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1 rud grd I > 60 de ani Orice metod de la
sau 2 rude grd 2 cu risc mediu la 5 ani _____________________________________
CCR _____________________________________
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Recomandri de screening i _____________________________________

supraveghere _____________________________________
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Risc nalt
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- FAP sigmoidoscopie anual ncepnd de la vrsta de
10- 12 ani _____________________________________
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- 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 _____________________________________
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- BII colonoscopie cu biopsii multiple anual sau la 2 ani
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(dup 8 ani)
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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
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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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 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
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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
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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 - ARN-
VHC 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!
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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
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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 rezisten-
se 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
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144
 HEPATITA CRONIC
VIRAL B
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Epidemiologie
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Peste 350 milioane persoane purttoare de Ag HBs pe _____________________________________
glob
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Prevalen:
_____________________________________
- sczut (<2%): Europa de Vest, SUA, Canada, Australia, Noua
Zeeland _____________________________________
- medie (2-7%): ri mediteraneene, Japonia, Asia Central, Orientul _____________________________________
Mijlociu, America Latin; Romnia 6%
_____________________________________
- ridicat (> 8%): Asia de Sud, China, Africa
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Spectrul bolii: purttor cronic inactiv hepatit cronic _____________________________________
ciroz hepatic - hepatocarcinom _____________________________________
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Virusul hepatic B _____________________________________

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
Mod de transmitere:
- vertical (mame Ag HBs +)
- orizontal (n special n ariile endemice)
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 _____________________________________
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Factori de risc pentru transmiterea VHB:
_____________________________________
- transmiterea vertical
_____________________________________
-activitatea sexual cu risc crescut (parteneri
sexuali multipli, homosexualitate) _____________________________________
-droguri intravenoase _____________________________________
-hemodializa
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-ariile de nalt endemicitate
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-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
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
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
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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 _____________________________________
Complicaii i mortalitate
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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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Mortalitatea (5 ani): _____________________________________
n hepatita cronic B 0-1 %;
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n ciroza hepatic viral B compensat 14-20%;
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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
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vrsta diagnosticrii (istoric lung de boal)
sexul masculin _____________________________________
episoadele recurente de reactivare a hepatitei _____________________________________
severitatea bolii hepatice n momentul diagnosticrii _____________________________________
Factori externi _____________________________________
alcoolul
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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
Diagnosticarea unor posibile coinfecii: VHD, VHC, HIV (la
cei cu risc)
Vaccinarea pentru hepatita A n ariile cu prevalen crescut
- la toi pacienii cu infecie cronic VHB i cu anticorpi anti
hepatit A abseni
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 non-
invaziv (FibroMax)
Hemogram, funcia hepatic
Ecografie, EDS (criterii de HTP)
Obiectivele tratamentului
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)
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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2. Ciroza hepatic viral B _____________________________________
- compensat: ADN VHB 2000 UI/ml indiferent de _____________________________________
statusul HBe
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- 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
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

Interferonul pegylat -2a
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)
Suprim replicarea viral, stimuleaz rspunsul imun
Nu induce rezisten
Contraindicaii, efecte secundare la fel ca n
tratamentul VHC (depresia mai rar!)
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
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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 Efecte secundare AN
Rezistena viral
- ridicat la lamivudin (65-70% la 5 ani!)
- intermediar la telbivudin i adefovir
- joas pentru entecavir i tenofovir
n cazul apariiei rezistenei se prefer
Strategii add-on cu clase diferite
Preferabil vs. switch
AN au eliminare renal; se recomand ajustarea dozelor
n caz de clearance de creatinin sczut
Profilul de siguran pe termen lung sau n cazul
asocierilor de AN nu este pe deplin cunoscut!
Lamivudina
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
Entecavir
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
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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Transplantul hepatic
Singura opiune la pacienii cu boal hepatic n stadii
terminale
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
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?
B +D
HEPATITA CRONIC
VHD virus satelit, dependent de VHB pentru producerea
proteinelor de nveli
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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Markerii infeciei active VHD _____________________________________
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Ig M anti VHD (diferenierea ntre
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suprainfecie/coinfecie se face prin absena/prezena
IgM anti HBc) _____________________________________
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ARN VHD _____________________________________
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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 necro-
inflamatorie 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
Peginterferon 2a sau b,1 an; RVS 25 40%
AN nu au eficacitate
Transplant hepatic
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 FICATUL GRAS
NONALCOOLIC
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Definiie. Termeni _____________________________________
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Acumularea hepatocelular de trigliceride n absena
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consumului semnificativ de alcool
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Ficatul gras non-alcoolic (nonalcoholic fatty liver disease _____________________________________
- NAFLD) include: _____________________________________
- steatoza
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- 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) _____________________________________
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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
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 omental-
stimuleaz utilizarea glucozei i oxidarea acizilor grai;
se coreleaz invers cu sindromul metabolic, insulino-
rezistena i NASH
Clasificarea morfologic
(Matteoni)
1. Steatoz simpl (absena inflamaiei i fibrozei)
2. Steatoz cu prezena inflamaiei lobulare dar cu
absena fibrozei sau a celulelor balonizate
3. Steatoz + inflamaie + degenerare balonizat
4. Steatoz + inflamaie + fibroz (caracteristic
perivenular i perisinusoidal) + celule balonizate +
corpi hialini Mallory
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Diagnostic clinic
Nu exist manifestri clinice specifice!
Majoritatea pacienilor sunt asimptomatici
Astenie, jen dureroas n hipocondrul drept
Hepatomegalie 75% din cazuri
n evoluie semne de hepatit cronic sau ciroz
hepatic
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)
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!
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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Diagnostic pozitiv _____________________________________
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istoric negativ pentru consumul de alcool _____________________________________
markeri virali negativi
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obezitate, DZ, hiperlipemie
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hepatomegalie
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cretere moderat ALT, AST
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fosfataza alcalin normal
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creteri moderate pentru GGTP
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echografic steatoz hepatic o ciroz
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Diagnostic diferenial _____________________________________
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Hepatita alcoolic
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Hepatite virale
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Hepatita autoimun
Hepatite medicamentoase _____________________________________
Hemocromatoz _____________________________________
Afeciuni tiroidiene _____________________________________
Boal Wilson
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Deficitul de alfa 1 antitripsin
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Evoluie. Complicaii.
Prognostic
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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Tratament
1. Scderea n greutate
Msuri igieno dietetice (diet, exerciiu fizic)
Terapie medicamentoas: orlistat, sibutramin
Chirurgie bariatric (indicat la IMC > 40)
2. Scderea rezistenei la insulin
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
Tratament
3. Combaterea stressului oxidativ
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
Tratament
4. Hipolipemiante
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
5. Transplant hepatic
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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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 BOALA HEPATIC
ALCOOLIC
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
Factori de risc
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
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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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)
Denutriia, carenele proteice i hipovitaminozele
preexistente sunt accentuate de consumul de alcool
accelereaz instalarea i decompensarea cirozei i
apariia hepatocarcinomului
Consumul de medicamente hepatotoxice
(acetaminofenul, hidrazida, droguri diverse)
poteneaz efectele nocive ale alcoolului
precipit instalarea cirozei hepatice
Obiceiuri:
Tipul de alcool consumat. Berea i buturile spirtoase sunt
mai nocive comparative cu vinul
Consumul de buturi alcoolice n afara meselor este mai
periculos dect n timpul meselor
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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Diagnostic
Anamneza + examen clinic + examen biochimic
+ explorare imagistic PBH
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
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
Afectarea hepatic parte din afectarea poliorganic din
alcoolismul cronic (cardiomiopatia alcoolic, pancreatita
alcoolic, neuropatia alcoolic etc.)
Examenul clinic - stadiului evolutiv al bolii hepatice cronice
(steatoz hepatic ciroz alcoolic complicat) + semne
specifice consumului de alcool (contractur Dupuytren,
hipertrofia parotidelor, feminizare etc)
Umoral biochimic
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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Explorri imagistice
nu precizeaz etiologia
evideniaz stadiul evolutiv al afeciunii hepatice :
decompensarea cirozei, hepatocarcinom, etc
explorarea de prim intenie - echografia
CT, RMN - n cazuri selecionate
PBH
etiologie incert a afeciunii hepatice
dac exist asociat bolii hepatice alcoolice o alt afeciune
hepatic
Diagnostic diferenial - afeciuni hepatice cu alt
etiologie
Complicaii ale cirozei hepatice, indiferent de etiologie
Evoluie i prognostic
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%)
Tratament
Abstinena - cheia terapeutic n boala hepatic alcoolic
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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Pentoxifilina 400 mg x3/zi - previne apariia sindromului
hepatorenal la pacienii cu scor Maddrey > 32
Enteroceptul i alte antiTNF necesit studii pentru a putea fi
recomandate n hepatita alcoolic
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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166
 HEPATITELE AUTOIMUNE
Definiie i date generale
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
Diagnostic pozitiv (1 -3)
1. Simptome clinice:
- orice form de hepatit cronic fr etiologie
- simptome nespecifice (astenie, artralgii, sindrom dispeptic
trenant)
- semne sau simptome ale altor afeciuni autoimune asociate
(de la tiroidit cu hipo- sau hiperfuncie, RCUH, DZ, vitiligo,
miastenia gravis etc.)
Examen obiectiv - concordant stadiului evolutiv: stigmate de
suferin hepatic hepatosplenomegalie icter ascit
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 2. Date de laborator i serologice
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)
3. Puncia biopsie hepatic:
- hepatit de interfa + inflitrat limfoplasmocitar n
spaiul port + arii de necroz hepatocitar (piecemeal
necrosis)
- hepatocitele - degenerescen vacuolar, canalicule
biliare de neoformaie, corpi acidofili
Diagnostic diferenial
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
Forme clinice de HAI
Tip I - caracteristici principale:
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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Tip II- caracteristici principale:
afecteaz preponderent copiii
imunglobulinele - valori extrem de crescute
asociaz alte afeciuni imune
evolueaz extrem de frecvent spre ciroz
prezint LKM1 i/sau LC1
Tipul III Ac SLA - considerat n prezent o variant a tipului I
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
Criterii pentru tratamentul imunosupresiv
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
Tratamentul standard
3 scopuri principale:
inducere i meninerea imunsupresiei (cu minime efecte
adverse)
prevenirea i tratamentul cirozei hepatice
Monoterapie (Prednison)
Biterapie (Prednison cu Azatioprin)
- se prefer biterapia cu monitorizare ntruct efectele
secundare sunt reduse comparativ cu monoterapia
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Tratamentul standard
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
Efectele adverse ale tratamentului standard
Efecte adverse ale corticoterapiei: cosmetice (acnee,
facies Cushingiod, vergeturi), obezitate, osteoporoz,
psihoz, depresie, DZ, cataract, hipertensiune arterial
Efecte adverse ale azatioprinei: greuri, vrsturi,
dureri abdominale, hepatit toxic, pancreatit, erupii
cutanate, artralgii, mialgii, leucopenie, teratogenicitate,
risc >1,4 pentru cancere extrahepatice
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
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
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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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
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1.Morfologic
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- micronodular (Laennecs) - noduli <3 mm, cel mai frecvent
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n etiologia alcoolic
- macronodular - noduli > 3mm, n etiologia viral B, C _____________________________________
- mixt - asociaz ambele aspecte _____________________________________
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173
 _____________________________________
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
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B Ag HBs, Ac anti HBc, viremie
C Ac anti VHC, viremie _____________________________________
D Ac anti VHD, viremie _____________________________________

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
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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,
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capacitatea de munc pastrat, diagnosticul fiind
ntmpltor _____________________________________
istoric lung de suferin hepatic _____________________________________
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Examen obiectiv _____________________________________
- poate fi normal sau stigmate de afeciune cronic _____________________________________
hepatic
_____________________________________
- stelue vasculare, circulaie colateral abdominal,
contractur Dupuytren etc _____________________________________
- hepatosplenomegalie _____________________________________
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174
 Explorri paraclinice
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)
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
Explorarea imagistic
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
Ecografia Doppler
permeabilitate vene suprahepatice, tromboz complet/
incomplet ven port vascularizaie formaiuni hepatice
Computer tomografia i rezonana magnetic nuclear
informaii suplimentare; cazuri selecionate
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9
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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)
Puncia biopsie hepatic
percutan (cel mai frecvent) / transjugular
confirm diagnosticul
Tratament
Msuri generale
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)
igiena dentar - prevenire infecii
evitarea medicamentelor hepatotoxice (citirea prospectului!)
imunizarea. Se recomand:
- vaccinuri VHA, VHB - precoce - eficiena scade paralel cu
evoluia bolii (n CH avansat - doz dubl)
- grip - vaccinare anual
osteoporoza - evaluare i tratament
monitorizarea afeciunilor asociate - creterea calitii vieii
pacientului cirotic
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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
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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
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

Tratamentul HDS prin efracie
variceal
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
I. Prevenia primar a HDS prin efracie
variceal
A. Farmacologic
B. Endoscopic
A. Tratamentul farmacologic
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
2. Nadolol 80mg /zi, Timolol, Carvedilol
B. Tratamentul endoscopic
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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II. Tratamentul HDS active prin efracie
variceal
oprirea sngerrii
Scop: corectarea hipovolemiei
prevenirea complicaiilor sngerrii active
prevenirea deteriorrii funciei hepatice
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
2.Tratament farmacologic
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)
- 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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3.Tratament endoscopic _____________________________________
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Se practic la toi pacienii cu sngerare activ prin efracie
variceal _____________________________________

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
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
 _____________________________________
6.Obliterare percutan transhepatic - varicele _____________________________________
gastrice _____________________________________
- sclerozare sau embolizare
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- controleaz 70% din sngerri
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7. unturi porto-sistemice chirurgicale _____________________________________
- mortalitate - 40% (efectuat n urgen)
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- 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 _____________________________________

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- curativ
- la pacienii cu boal terminal _____________________________________
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29
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HDS prin efracia varicelor gastrice
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
30
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181

HDS prin gastropatia portal -
hipertensiv
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
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
Ciroz fr terapie profilactic
primar
Ciroz cu sngerare sub terapie cu
blocant
Contraindicaii sau intoleran la
blocante
Eec al profilaxiei secundare
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blocant i/sau ligatur
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blocant + ligatur
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Ligatura este preferat pentru _____________________________________
prevenirea resngerrii
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TIPS; transplant hepatic
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182
 COMPLICAIILE CIROZEI
HEPATICE

ASCITA

34

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ASCITA
(askos = geant, sac) _____________________________________
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acumulare de lichid n cavitatea peritoneal
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este cea mai frecvent complicaie a CH
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riscul de apariie la pacienii cirotici - 5 -7 % ~60% din
pacienii cu CH compensat vor face ascit la 10 ani de la _____________________________________
diagnostic
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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,
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sindrom hepatorenal) care scad supravieuirea
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35
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_____________________________________
Diagnostic clinic _____________________________________

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
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- hepatosplenomegalie 36
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183
 _____________________________________
Explorri paraclinice _____________________________________
A . Funcia hepatic:
sindromul de citoliz _____________________________________
Alterarea celor sindromul bilioexcretor
4 sindroame hepatice sindromul hepatopriv _____________________________________
sindromul de iritaie mezenchimal _____________________________________
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) _____________________________________
D. Tomografie computerizat n cazuri selecionate _____________________________________
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E. EDS - varice esofagiene, gastropatie portal hipertensiv 37
_____________________________________

F. Paracenteza diagnostic
- locul puncionrii linia spino-ombilical sng
- 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
obezitate, meteorism, glob vezical, uter gravid, tumori
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
39
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184
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
II.albumina seric /albumina ascit < 1,1 g/dl:
carcinomatoza peritoneal, TBC peritoneal, sindromul
nefrotic, cauze rare (ascita biliar, pancreatic, boli de
colagen)
Tratamentul ascitei din CH
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
- encefalopatie
- Na seric < 120 mEq/L dup restricie hidric
Diureticele se opresc:
- creatinina > 2 mg/dl
- hiperpotasemie, acidoz metabolic( spironolactona)
Ascita refractar
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)
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
185
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Tratamentul ascitei
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
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%
186
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 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
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Mecanisme patogene n PBS _____________________________________
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Sursa de infecie: colonul, tractul urinar, respirator, pielea
3 mecanisme patogene: _____________________________________
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Translocarea bacterian din intestin n ganglionii
limfatici mezenterici _____________________________________
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Scderea activitii fagocitare n sistemul
reticuloendotelial, considerat mecanism esenial n _____________________________________
colonizarea i persistena bacteremiei n ciroza
hepatic _____________________________________
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Reducerea mecanismelor de aprare bacterian n
lichidul de ascit _____________________________________
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187
 _____________________________________
Factorii precipitani n PBS _____________________________________

Confirmai: _____________________________________
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insuficien hepatic sever, clasa C Child _____________________________________
ascit sub tensiune
HDS _____________________________________
concentraia proteinelor n lichidul de ascit < 1 g/dL _____________________________________
episod anterior de PBS
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Na < 130 mEq/L
creatinin > 1,5 mg/dl _____________________________________
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48
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Factori posibili, dar neconfirmai: _____________________________________
infecii tract urinar _____________________________________
cateterismul vezicii urinare
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cateterism intravenos
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paracentezele voluminoase
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Factori improbabili: paracenteza, endoscopia hemostaza _____________________________________
endoscopic, hepatocarcinomul
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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 toxico-
septic
Investigaii paraclinice sanguine: leucocitoz, afectare
funcional hepatic sever (insuficien hepatic clasa C
Child) i insuficien renal n 1/3 din cazuri
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n prezena acestor simptome, diagnosticul de
certitudine : analiza lichidului de ascit: _____________________________________
polimorfonucleare (PMN) i cultur _____________________________________
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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
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Diagnostic diferenial _____________________________________
Diagnosticul de peritonit bacterian secundar prin _____________________________________
perforarea unui viscer (beneficiaz de tratament
chirurgical!) _____________________________________
PMN > 250 /mm3 _____________________________________
pluribacterian
proteine totale > 1g/dl
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glucoz > 50 mg/dl _____________________________________
LDH > 225 UI/ml
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la tratament PMN i culturile se normalizeaz n 48 h n PBS, nu
i n cea secundar _____________________________________
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Bacterascita plurimicrobian: < 250 PMN, pluribacterian,
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apare (1/1000 cazuri) dup puncionarea intestinului n timpul
paracentezei diagnosticeparacentezei diagnostice: _____________________________________
53
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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
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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
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 COMPLICAIILE CIROZEI
HEPATICE

SINDROMUL HEPATO - RENAL

58

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Definiie : insuficien renal funcional, potenial
reversibil cu/fr transplant hepatic, care apare n ciroza _____________________________________
hepatic cu ascit sub tensiune i insuficien hepatic _____________________________________
sever
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Incidena anual este de 8%
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Factori favorizani: _____________________________________
infeciile bacteriene _____________________________________
hemoragiile digestive _____________________________________
paracentezele voluminoase (>5 l)
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interveniile chirurgicale
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medicamentele nefrotoxice
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59
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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
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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 6-8-
12 luni, direct proporional cu gradul insuficienei
hepatice
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
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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
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 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
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Diagnostic
Presiunea n artera pulmonar > 25 mm Hg
Rezistena vascular pulmonar > 240 dyne/s/m
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Diagnostic diferenial: _____________________________________

Trombembolism pulmonar _____________________________________

Boal pulmonar interstiial _____________________________________
Boal de esut colagenic _____________________________________
Apnee de somn netratat _____________________________________
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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
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
196
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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
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 COMPLICAIILE CIROZEI
HEPATICE
CARDIOMIOPATIA CIROTIC
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
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 COMPLICAIILE CIROZEI
HEPATICE
ENCEFALOPATIA HEPATO
PORTAL (EHP)
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
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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)
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Diagnostic pozitiv : simptome neuropsihice la un pacient _____________________________________
cunoscut cu ciroz hepatic _____________________________________
Tabloul clinic asociaz: _____________________________________
1. Semne de insuficien hepatic:
- fetor hepatic (mercaptani)
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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
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- modificarea intelectului: scderea capacitii de concentrare,
apraxie, modificarea scrisului _____________________________________
- neurologice: asterix sau flapping tremor
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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
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redus
CT( atrofie cerebrala difuz n etiologia alcoolic) _____________________________________
n cazuri selecionate: _____________________________________
RMN _____________________________________
Spectroscopia de rezonan (structura metabolismului
cerebral) _____________________________________
Tomografia cu emisie de pozitroni _____________________________________
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Diagnostic EHP minim _____________________________________
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Examen neurologic obinuit normal
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Alterarea testelor psihometrice (de la orientarea n timp
i spatiu pn la conexiuni numerice ) _____________________________________
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Alterarea testelor neurofiziologice (poteniale evocate) i _____________________________________
nregistrarea modificrilor EEG determinate de stimuli
diveri (vizuali, auditivi, etc) _____________________________________
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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
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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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
203
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 COMPLICAIILE CIROZEI
HEPATICE
HEPATOCARCINOMUL
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
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
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 Prognosticul CH _____________________________________
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Scor Child-Pugh _____________________________________
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Encefalopatie absent 1 _____________________________________
stadiul 1-2 2 _____________________________________
stadiul 3-4 3
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Ascit absent 1
minim( cu rspuns la diuretice) 2 _____________________________________
refractar 3 _____________________________________
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INR < 1.7 1
1.7-2.3 2 _____________________________________
> 2.3 3 _____________________________________
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Albumin (g/dL) > 3.5 1
2.8-3.5 2 _____________________________________
< 2.8 3
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Bilirubina (mg/dL) <2 1 _____________________________________
2-3 2 _____________________________________
>3 3
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Clasa A - scor 5-6
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- 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
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- supravieuire la 1 an 45%
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205
206
 CANCERUL HEPATIC
PRIMITIV
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
- creterea HCC n zone cu risc mediu (Japonia,Europa de V)
explicaii posibile: creterea duratei de viata n CH
tehnici imagistice performante
Etiopatogenie
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
207
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Infecia cronic cu VHB
- 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%
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
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
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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 Alte afeciuni hepatice
- steatohepatita non alcoolic nonviral
- hepatitele autoimune, boala Wilson, CBP riscul de HCC
este dificil de cuantificat
Dieta aflatoxinele (contaminare Aspergillus flavus i
parasiticus)
- suprancarcare fier (recipiente de preparat/stocat -
Africa)
- algae blue green (heletee i lacuri) peptide
ciclice hepatotoxice China
Factori de risc posibili
Tutunul
Alcoolul
Contraceptive orale cu doze ridicate de hormoni steroizi
7
Tablou clinic
HCC - complicaie frecvent n CH simptomatologia
proprie mascat de cea a bolii de baz ( one patient
two diseases)
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
Examenul clinic obiectiv
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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Explorarea paraclinic
1. Explorarea funcional hepatic:
- alterarea funciei hepatice cu modificarea celor 4 mari
sindroame (hepatocitoliz, colestaz, hepatopriv, reactivitate
mezenchimal)
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).
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
Ali markeri tumorali: HCC incipient - glypican 3
HCC avansat - betacatenin
NB: Nu sunt folosii n practica curent.
4. Examenul histopatologic
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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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
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.
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
Ecografie (consensuri)
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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Diagnostic diferenial _____________________________________
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
_____________________________________

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 Scor _____________________________________
. supravieuire Stadiul I = 0 - supravieuire 8 luni
Dimensiuni 0 Stadiul II = 1-2 - supravieuire 1-3 luni _____________________________________
< 50% din ficat
Stadiul III = 3-4 supravieuire 0,5-2 luni
Dimensiuni 1 _____________________________________
> 50% din ficat
Ascit absent 0 _____________________________________
Ascit prezent 1 _____________________________________
Albumin seric 0 _____________________________________
> 30 g/l
Albumin seric 1 _____________________________________
< 30 g/l
Bilirubin 0 _____________________________________
< 3 mg/dl
Bilirubin 1 _____________________________________
> 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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212

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
Chirurgia de rezecie este o alternativ fiabil atunci
cnd sunt ndeplinite criteriile de rezecabilitate
- 10 - 30 % din cazuri
curativ larg, dac nu asociaz CH
paleativ segmentectomii, enucleere - dac leziunea
este extins; recidiv tumoral crescut
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)
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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Chimioterapia sistemic _____________________________________
rezultate puin promitoare n prezent; studii n _____________________________________
desfurare
cea regional (intraarterial hepatic) se poate _____________________________________
recomanda n cazuri selecionate _____________________________________
_____________________________________
Terapii moleculare: Sorafenib (inhibitor oral multikinazic)
(HCC - hipervascularizat) 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

Definiie: inflamaia acut a peretelui vezicii biliare
n peste 90% din cazuri complic litiaza biliar
vezicular
litiaza biliar vezicular este simptomatic numai n
15-20% din cazuri
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215

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
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
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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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
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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
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 non-
invaziv), ERCP, ecoendoscopie
tratament: ERCP cu sfincterotomie i extracie de
calculi
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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Tratament
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
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
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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 SINDROMUL
POSTCOLECISTECTOMIE

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: _____________________________________
_____________________________________
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,
Disfunciile sfincterului Oddi proteze biliare) _____________________________________
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220
 TUMORI MALIGNE ALE
ILOR BILIARE
C

Cancerul veziculei biliare i colangiocarcinomul sunt
entiti tumorale distincte care au n comun originea
embrionar i parte din factorii etiologici
Prognosticul este rezervat
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
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)
Factori de risc
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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 Tablou clinic
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)
Diagnostic pozitiv
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 loco-
regional 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
Stadializare
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
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Tumorile benigne veziculare
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Colangiocarcinomul
HCC _____________________________________
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Prognostic _____________________________________

- Rezervat (tumor rapid metastazant cu simptomatologie _____________________________________

necaracteristic)! _____________________________________
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Tratament
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
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
Tablou clinic
simptome clinice n general nespecifice
prurit (datorat icterului obstructiv)
durere abdominal necaracteristic, adesea singurul
simptom
semne de impregnare neoplazic (scdere ponderal,
anorexie, etc)
Examenul obiectiv:
- icter leziuni de grataj
- hepatomegalie
- vezicul biliar palpabil n localizarea distal a
colangiocarcinomului
225
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 Diagnostic pozitiv
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
Stadializare
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)
Diagnostic diferenial
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)
Prognostic
- rezervat
- n tumorile nerezecabile indiferent de localizare, media
de supravieuire este de 8 12 luni
226
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 Tratament
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
227
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228
 PANCREATITA ACUT

Definiie: episod inflamator acut rezultat din
activarea intrapancreatic a enzimelor digestive
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 necrotico-
hemoragic
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Etiologie
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Cauze frecvente
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- litiaza biliar
75 85% din PA _____________________________________
- consumul de alcool
- hipertrigliceridemia _____________________________________
- ERCP _____________________________________
- traumatisme abdominale _____________________________________
- postoperator (intervenii chirurgicale abdominale i non- _____________________________________
abdominale, 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
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)
Fiziopatologie
Faza enzimatic (de declanare) activarea
intrapancreatic a enzimelor digestive i lezarea celulelor
acinare
Etapa rspunsului inflamator local (cascada rspunsului
inflamator)
Etapa rspunsului inflamator sistemic (PAF, TNF, Il 6
etc) i a insuficienei multiple de organ
Faza de restituie
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
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)
Diagnostic clinic
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
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
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
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
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Extradigestive
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Sarcin extrauterin rupt
Anevrism/disecie aort _____________________________________
Insuficien renal _____________________________________
Cetoacidoz diabetic _____________________________________
Arsuri
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Afeciuni ale glandelor
salivare _____________________________________
Cancer esofagian, _____________________________________
pulmonar, ovarian
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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
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
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
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)
233
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Diagnostic pozitiv
Cel puin 2 din 3 criterii:
Clinic (durere, greuri, vrsturi)
Biologic ( amilaze, lipaze > 3 x N)
Imagistic (CT, rezonan magnetic)
Diagnostic diferenial
Colecictita acut
Colic biliar coledocolitiaz
Perforaie intestinal
Ulcer peptic perforat
Ocluzie intestinal acut
Hepatit alcoolic
Hepatit viral
Criteriile Ranson n PA
La internare
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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Ischemie/infarct mezenteric _____________________________________
Vasculite _____________________________________
Disecie, anevrism aort
Infarct miocardic _____________________________________
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Pneumonie
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Colic renal
Apendicit acut _____________________________________
Cetoacidoz diabetic _____________________________________
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Dificile, necesit
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48 ore pentru
aprecierea _____________________________________
prognostic
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234

Criterii de severitate (Atlanta)
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)
Complicaii
Locale
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
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)
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
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)
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
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 naso-
jejunal), preferabil nutriiei parenterale totale
Tratament
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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Tratamentul necrozei pancreatice
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 5-
7 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)
Tratamentul pseudochistelor pancreatice
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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238
 PANCREATITA CRONIC
Definiie
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
Etiologie-TIGAR-O
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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Morfopatologie
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
Fiziopatologie
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
Fiziopatologie
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
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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Diagnostic clinic
Aproximativ jumtate din pacieni prezint episoade
recurente de pancreatit acut
1. Durere
2. Malabsorpie
3. Diabet zaharat
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
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
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3. Diabetul zaharat
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)
Diagnostic paraclinic
1. Explorri biochimice
- 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
2. Explorri imagistice
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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 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
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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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%
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)
Diagnostic diferenial
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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 Complicaii
Locale
Pseudochisturi
pancreatice
Abcese
Stenoz coledocian
Obstrucie duodenal
Tromboz de ven port, Necroze lipidice
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
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Ulcer gastric sau
duodenal _____________________________________
Serozite (ascit, _____________________________________
pleurezie, pericardit) _____________________________________
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metastatice
Necroze aseptice de cap _____________________________________
femural, humeral _____________________________________
Retinopatie non-diabetic
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(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
Imagistic Tipic: mrirea difuz a pancreasului cu inel periferic (CT,
RMN); neregularitate difuz a canalului pancreatic
(MRCP, ERCP)
Serologie Ig G4
Afectarea Stricturi biliare intrahepatice sau la nivelul coledocului
altor organe distal, afectarea glandelor parotide/lacrimale, adenopatii
mediastinale, fibroz retroperitoneal
Rspuns la Rezoluia/ameliorarea manifestrilor
corticoterapie pancreatice/extrapancreatice la corticoterapie
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Tratament _____________________________________
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Tratamentul:
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A. Durererii
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B. Malabsorbiei
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C. Diabetului zaharat
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A. Tratamentul durerii _____________________________________
_____________________________________
Mecanismele durerii: inflamaia acut, creterea presiunii
intrapancreatice, inflamaia neural _____________________________________
_____________________________________
Opiuni terapeutice: _____________________________________
- analgetice
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- ntreruperea consumului de alcool
- inflamaiei _____________________________________
- presiunii intrapancreatice ( secreiei, ndeprtarea _____________________________________
obstruciei)
- modificarea transmiterii neurale _____________________________________
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 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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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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 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
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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
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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 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
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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)
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Forme clinico topografice n CP
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Cancer de cap de pancreas _____________________________________
- icter progresiv + prurit
- scdere n greutate _____________________________________
- hepatomegalie
- semnul Courvoisier- Terrier
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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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 Stadializarea CP _____________________________________
Tis - carcinom in situ _____________________________________
T1 - tumor limitat la pancreas 2cm
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T2 - tumor limitat la pancreas > 2cm
T3 - tumor extins direct n duoden, ci biliare, esutul _____________________________________
peripancreatic
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T4 - tumor extins direct n stomac, splin, colon, vase mari
adiacente _____________________________________
N0 - fr metastaze ganglionare regionale
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N1 - cu metastaze ganglionare regionale
M0 - fr metastaze la distan _____________________________________
M1 - metastaze la distan
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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
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Umoral - biochimic: nVSH, n glicemie, sindrom de _____________________________________
colestaz ( FA, GGTP, bilirubina)
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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
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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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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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