Gastricand

duodenal ulcers

Definition
Itisachronicandrecurrentdisease
Itischaracterizedbyalesion(ulcer)ofthe
gastroduodenalmucosa,usuallyround,which
penetratesthemucosaandsubmucosa,
reachinguptomuscularispropria
Gastriculcerisadeepgastricmucosallesion,
penetratingbeyondthemuscularmucosa,which
issimilarintermsofhistologywithduodenal
ulcers,butbeingsurroundedbyareasofmore
extensiveadjacentgastritis

Gastricand duodenal ulcers

Etiologyandpathogenesis
UDisconsideredtheresultofan
imbalancebetweenaggressiveand
protectivefactorsofgastroduodenal
mucosainfavorofaggressivefactors
(gastricacidandpepsin).

Gastricand duodenal ulcers

prevalence
6-15%ofthewesternpopulation.
10%ofthepopulationlivesalongwiththe
clinicalmanifestationsofulcer.
Itisadiseasemorecommoninmen

Gastricand duodenal ulcers

Studiesinrecentyearshaveimposedrole
ofHelicobacterpylori(HP)inthe
pathogenesisofpepticulcer.
At95-100%ofpatientswithduodenal
ulcerwereidentifiedmarkersforinfection
withHP,aswellas75-85%ofpatientswith
gastriculcer.

Modeoftransmissionofinfectionislargely
unknown,butepidemiologicaldatashowa
way
-fecal-oral
-oral-oralor
-gastro-oral.
Helicobacterpylori(HP)isapathogenic
bacterium.

HPinfection
InitialinfectionwithHPisfollowedbyan
acutegastritis,antralpredominant,but
usuallyaffectsthebodyofthestomach.
Thisphaselastsforweeksormonths,
afterwhichuntreatedcanturnintoa
chronicgastritis.
Inflammatorychangescontinue,evenin
thisstagewillbeusedasagastricatrophy

HPinfectionisclassifiedasaclassI
humancarcinogen.
Helicobacterpyloricolonizesonlythe
gastricepithelium,nottheduodenum.
PresenceofHelicobacterpyloriin95100%ofUDismadebyislandsgastric
metaplasiainduodenalmucosa.

pathogenicaction
H.pyloricansynthesizeavarietyofproteinsthatappear
tomediateitseffectsongastricmucosaaggressive.
Aggressionongastricmucosaduetoproductionof
toxins(citovac=vacuolatingcytotoxin)andsome
enzymesthathydrolyzeurea(NH2)2CO3,ubiquitous
substanceinthehumanbody.
Helicobacterpyloriproducestheproteinsurfaceandis
chemotacticformonocytes,polymorphonuclearalso
secreteplateletactivatingfactor,whichisproinflammatory
Theorganismproducesproteasesandphospholipase
thatdegradesglyco-protein-lipidcomplexlayerofmucus.

PathogenesisofDU

ThereasonforH. pylorimediatedduodenalulcerationremainsunclear.
StudiessuggestthatH. pyloriassociatedwithduodenalulcerationmaybe
morevirulent.
Inaddition,certainspecificbacterialfactorssuchastheduodenalulcerpromotinggeneA(dupA),maybeassociatedwiththedevelopmentof
duodenalulcers.
Another potential contributing factor is that gastric metaplasia in the
duodenum of DU patients, which may be due to high acid exposure
witch permits H. pylori to bind to it and produce local injury
secondary to the host response.

AnotherhypothesisisthatH. pyloriantralinfectioncouldleadto
increasedacidproduction,increasedduodenalacid,andmucosal
injury.Basalandstimulatedmeal,gastrin-releasingpeptide(GRP)]
gastrinreleaseareincreasedinH. pyloriinfectedindividuals,and
somatostatin-secretingDcellsmaybedecreased.
H. pyloriinfectionmightinduceincreasedacidsecretionthrough
bothdirectandindirectactionsofH. pyloriandproinflammatory
cytokines(IL-8,TNF,andIL-1)onG,D,andparietalcells

FinallyHelicobacterpyloriproduces
inflammation,attractneutrophils,
stimulatesthereleaseofgastrinfrom
antralGcells,inducingahyperacidityin
theearlystagesofinfectionwithHP

FinallyHelicobacterpyloriproduces
inflammation,attractneutrophils,
stimulatesthereleaseofgastrinfrom
antralGcells,inducingahyperacidityin
theearlystagesofinfectionwithHP

Increasedgastricacidity
Classichydrochloricacidandpepsinarethemost
importantaggressivepathogeneticfactorforduodenal
ulcer.
Classicalstudieshaveshownthatpatientswithduodenal
ulcergastrichaveacidityhigherthannormal.
Increasedgastricacidsecretioninpatientswith
duodenalulcerdependstheinfectionwithHelicobacter
pylori,butalsobyotherfactors(gastrin,somatostatin,
etc.).
AftereradicationofHPinfectionthelevelofgastrin
serumandDABreturningslowlytonormal,althoughit
mayremainslightlyincreasedDAM.

Otherpathogeneticfactorin
duodenalulcer
Rapidemptyingofthestomachaftermeals
AnotherdisorderiscommoninpatientswithUDandis
associatedwithgastricacidhypersecretionrelative.
Acidificationsteeperproximalduodenumcausing
reducedbicarbonatesecretionintheduodenumand
gastricmetaplasiaalsofavoringduodenalmucosal
colonizationconsecutivethenHP.
Geneticfactor
UDareabout3timesmorecommoninfirst-degree
relativesofulcerpatientsthaninthegeneralpopulation.

Otherpathogeneticfactorin
duodenalulcer
Smoking
Smokinginhibitpancreaticsecretionrich
inbicarbonate,promotesrapidemptying
ofgastricacidintheduodenum,butthey
doesnotgrowdirectlysecretionofgastric
acid.
Hisroleremainstopromoteother
ulcerogenicfactors

Otherpathogeneticfactorin
duodenalulcer
Thecombinationofcertainconditions
Duodenalulcerhasahigherincidencein
patientswith
-chronicrenalfailure,renaltransplant
-alcoholiccirrhosis,
-hyperparathyroidism,
-systemicmastocytosis
-Chronicobstructivepulmonary.

Psychologicalfactors
Chronicanxietyandmentalstresscanbefactors
ofexacerbationofduodenalulceractivity.

Pathogenesis of Non-Hp and

Non-NSAID Ulcer
Disease Infection:Cytomegalovirus,Herpessimplex
virusH.heilmannii
Drug/ToxinBisphosphonates,Chemotherapy,Clopidogr
el,Crackcocaine,Glucocorticoids(whencombinedwith
NSAIDs)Mycophenolatemofetil,Potassiumchloride

MiscellaneousBasophiliainmyeloproliferativedisease,
Duodenalobstruction(e.g.,annularpancreas),Infiltrating
disease,Ischemia,Radiationtherapy,Sarcoidosis,
Crohn'sdisease,Idiopathichypersecretorystate

PATHOLOGY

Acuteduodenalulcerisusuallyasinglelesion
withadiameterof0.5to1cm
Rarelyduodenalulcerscanbeextremelylarge,
3-6cmindiameter(so-calledduodenalulcers
"giant")andmaybeconfusedradiologicwiththe
wholeduodenalbulb
Duodenalulcercanbemultiplein ZollingerEllisonSyndrome.
Macroscopiculcerappearsasasleekround
edges,unevenedema.
Ulcersaresharplydemarcated,withdepthat
timesreachingthemuscularispropria.

95%oftheulcersarelocatedinthe
proximalpartoftheduodenum
Othertypesofpepticulcer:
Chronicduodenalulcer,fibrosis,orulcer
callosum
Bleedingulcer,Therearepots,weathered
visibleendoscopic.

Clinicalsigns
Dispepticulcersyndromearecharacterizedby:
-rhythmicity
-periodicity
-characterofpain
-durationofpain
Thepainisaccompaniedby:
salivation
regurgitate,heartburn
nausea,vomitingacid,whichcanalsobesignsof
complications.
constipation.

Clinicalsigns
Besidestheabovesymptomscanalsobepresent,
duodenalulcerwithsignsofulcercomplications,
suggestionsbycharacterpainmodificationin:
Penetration:constantpain,unimprovedbyantacidsor
foodintake,radiatingtothebackorupperquadrants
perforation:livingpain,suddenonsetgeneralizedinthe
throughoutabdomen.Externalizationofupper
gastrointestinalbleedingisdoneby
-hematemesis,
-melena,
-hematocheziaor
-Chronicirondeficiencyofvaryingdegreesthrough
occultbleeding

Clinicalexamination
clinicalexamination
Oninspectioncanbeseenfacies"ulcer"
Onpalpationareseensensitivityin
epigastriummidwaybetweenthe
umbilicusandxiphoidappendixtotheright
ofthecentreline.

Laboratory
bariumexamination
70-80%ofulcerspresentsradiologicalsigns
suggestive.
Onduodenalbulb,nicheulcerlookslikea
discretlycrateronD1making
-Cockadeimageonsides
-deformationsduodenalbulbinchronicforms;
aspect"inclover"in"hammer
-gastrichypersecretionandhyperkinesia

Radiologicalaspectduodenalulcer
Nicebulbarbenign
Edemperiulceros

Laboratory
Gastric chemistry
Notnecessaryinduodenalulcerwhere
thereisusuallybasalandstimulated
hyperacidity.
InZollinger-Ellisonsyndromeishigh
hyperacidityinbasalconditions.

LaboratoryTesting

Patientswhorespondtooptimaltherapyforpepticulcer
diseasedonotrequirespecializedtesting.However,
thosewithrefractory(nothealedafter8weeksof
therapy)orrecurrentdiseaseshouldhaveserum
gastrinandserumcalciummeasuredtoscreenfor
gastrinomaandmultipleendocrineneoplasia(MEN).
Thesepatientsshouldalsoundergogastricacidanalysis
todeterminewhethertheulceriscausedbygastric
acidhypersecretion(basalacidoutputexceeding10
mEq/hr)ordecreasedmucosalprotection.

Patients with refractory or recurrent peptic

ulcer disease may have an underlying
Helicobacter pylori (H. pylori) infection.

Histological examination of biopsies

of the gastric antrum, obtained
during endoscopy, is the gold
standard for diagnosis of H. pylori.
Routinely, H. pylori is not cultured
because of the difficulty growing the
organism.

 Serologic tests are available, but unfortunately,

positive test results indicate only past exposure and
are not useful for determining if the infection has
been cured.
Urea breath tests are simple and noninvasive, and
have been used to diagnose H. pylori infection.
Because H. pylori produces large quantities of the
enzyme urease, these breath tests have the
potential to be quite useful. 13C- and 14C-urea
breath tests offer excellent diagnostic yield. Patients
ingest a solution containing 13C- or 14C-labeled
urea and an exhaled breath is sampled for isotopelabeled CO2 released by intragastric H. pylori
urease activity. The test can be completed within 20
minutes and is highly sensitive and specific .

BloodtestsforHelicobacter
pyloriinfectionisassumedinall
patientswithactiveduodenal
ulcerandthosewithfrequent
relapses,hencetheneedforantiinfectivetherapy.

Indicactions of gastrin measuring

Itisdesirabletomakeatpatientswhoareplanningforsurgeryorthosewith
suspectedgastrinom
Indicactions of gastrin measuring include:
Multipleulcersorulcersinunusuallocations,
ulcersresistanttotherapyorfrequentrelapses,
ulcersrequiringsurgery
Postoperativerecurrenceofulcers,
Signsofsevereesophagitis,
unexplaineddiarrheaorsteatorrhea,
hypercalcemia
Gastricorduodenalfoldsproeminenthypertrophicatendoscopic
examination

Endoscopy
Notrequiredifradiographs
showedniche.
Endoscopy shows ulcers, which can be
covered by a membrane of fibrin, any signs
of recent bleeding.
Endoscopyindicationsinduodenalulcers:
-Detectionofsuspectedulcersintheabsence
ofradiologicalimages.
-Thepresenceofradiologicalchanges
insecureulceractivity
-identificationofsmallorsuperficialulcers,
undetectableradiologically
-Identification/exclusionofactive
gastrointestinalbleeding

Ulcercomplications
perforation,
penetration,
pyloricstenosis,
GastrointestinalBleeding

Treatment
Thegoalsoftreatmentinduodenalulcer
are:
thehealingofthelesions
symptomsdisappear,
preventionofcomplications
Duodenalulcershealspontaneouslyin4-8
weeks!
itscomplicationshaveingeneralsurgery

Measureshygienic-dietetic
smokingcessation
reducingalcohol
avoidingcoffeeandcaffeinatedbeverages
waiver,reductiontherapy(NSAIDs).
Dietrequiresavoidingseasonings,pickles,
concentratedsweets,fruitorfoodthatgastric
intolerance
Thereisnoevidencethatdietlowersgastric
hyperacidityandacceleratesthehealingprocess

Measureshygienic-dietetic
smokingcessation
reducingalcohol
avoidingcoffeeandcaffeinatedbeverages
waiver,reductiontherapy(NSAIDs).
Dietrequiresavoidingseasonings,pickles,
concentratedsweets,fruitorfoodthatgastric
intolerance
Thereisnoevidencethatdietlowersgastric
hyperacidityandacceleratesthehealingprocess

Measureshygienic-dietetic
smokingcessation
reducingalcohol
avoidingcoffeeandcaffeinatedbeverages
waiver,reductiontherapy(NSAIDs).
Dietrequiresavoidingseasonings,pickles,
concentratedsweets,fruitorfoodthatgastric
intolerance
Thereisnoevidencethatdietlowersgastric
hyperacidityandacceleratesthehealingprocess

Treatment
1.AntibioticeforHelicobacterpyloriinfection
2.Reduceacidsecretion
-Acidsecretionblockers(cimetidine,ranitidine,
andfamotidine)
-Protonpumpinhibitors(ex.omeprazole)
-antacids
3.Medicationmucosalprotection
-MedicationsThatprotectthetissuelining(like
sucralfate)
-Bismuth(mayhelpprotecttheliningandkillthe
bacteria)

Treatment
Antacids:
-saltsofaluminumandmagnesium(Gelusil,Malox).are
themostwidelyusedatpresentintheformofgels,
mixtures,etc.
-Calciumcarbonateandsodiumbicarbonatearepotent
antacidswithvaryinglevelsofpotential
problems.Sodiumbicarbonatemayinducesystemic
alkalosis
Thelong-termuseofcalciumcarbonate(convertsto
calciumchlorideinthestomach)canleadtomilk-alkali
syndrome
Antacidmedicationindicationsarerapidlyimproving
subjectivesymptoms

Antisecretory
anticholinergics
Non-Selectiveanticholinergic:atropine,
probantelina(3x15mg)
Selectiveanticholinergic:pirenzepine
(gastrozepin3x25mg),whichactsonmuscarinic
M1receptorsinthestomachlining,reducing
acidsecretion.
Thereareindicationsinduodenalulcerwithout
duodenogastricreflux.
Sideeffects:drymouth,blurredvision,impaired
gastricemptying

Contraindications:glaucoma,prostateadenoma.

Antisecretory
H2-receptor antagonists
-H2receptorantagonistscompeteswith
histaminereceptorsonparietalcells,thus
blockingbasalandstimulatedacidsecretion
Cimetidine 3x200,2x400mg
Ranetidina2x150mg(Zantac)or300mgevening
Famotidine(Quamatel)2x20mg,hasanassociated
antirefluxeffect.
Nizatidine(Axid)indosesof300mgatnight.

Antisecretory
Antienzimatic drugs
Blocking carbonic anhydrase
Acetazolamide(Ulcosilvanil)isadrugoriginallyusedas
adiureticeffectblockingcarbonicanhydraseingastric
parietalcells(oxintice).
Doserequirementscarbonicanhydraseinhibitionof
gastricparietalcells,hasmanypotentiallydangerous
sideeffects.
Gastrin receptor antagonists
Proglumidul(urogastrona)isaspecificinhibitorofgastrin
receptorsonthesurfaceoftheparietalcells.

Antisecretory
Protonpumpinhibitors(PPIs)
Inhibitthefinalstageofhydrogenionsecretionbythe
parietalcells,whichismadebyATPazaH+/K+,or
"protonpump".
Proton;spumpinhibitorsaresubstitutedbenzimidazole
compoundsthatattachtoATPazaH+/K+irreversibly
theenzymeinactivnd
Theyproduceallphasesofprolongedinhibitionofgastric
secretion,gastricacidsynthesisregenerationrequires
thesynthesisofnewenzymes.
Alsoinhibitspepsinsecretion,favoringthedevelopment
ofnitrosaminesintragastric

Protonpumpinhibitors(PPIs)
Omeprozolul,2x20mg
Esomeprazole(Losec)2x20or40mginthe
evening
Lansoprazole(Levant)2x30mg
Pantoprazole(Controloc)40mgintheevening
2x20mg
SideeffectsofPPIsarelinkedtosharpdecrease
gastricacidityandexperimentalinductionof
gastriccarcinoidtumorsafterprolonged
administrationinrats,anddecreasedhepatic
metabolismofdrugs

Medicationprotectingthegastroduodenal
mucosa
Thetherapeuticarsenalantiulceroaslongbeen
usedanumberofsubstancesthatactprimarily
onthegastricmucosa.
Prostaglandins
Ithasbeenshownthatcertainprostaglandins,
especiallyPGE1andPGE2areeffectiveinthe
treatmentofduodenalulcers
OfprostaglandinsmentionMisoprostol(Cytotec)
usedat200,400mg2x400mgfortreatmentand
preventionofduodenalulcerscausedbyNSAID

Othergastricmucosalprotective
agents
Sucralfate(sucrose,saltThecombined)inthe
formofpackagesof1gistakenasthe4x1g/zi.
Carbenoxolone(Bigastrona)aLiquiritiaextract,
stimulatesthesecretionofmucusandhasgood
effectonulcerhealing.
Colloidalbismuth(De-Nolpreparation)inthe
formofbismuthsubcitrateisadministeredbefore
mese.Formeazabismuth-proteincomplexis
assumedthatprotectstheulcerbytheactionof
digestiveacidsandpepsin,stimulatethe
productionofmucus,andprostaglandins.

Antibacterialmedication
HPinfectiontreatmentisrecommended
forallpatientswithduodenalulcer

Recommendedfirst-linetripletherapy
(OACorOMC7days)orprotonpump
inhibitor(PPI)+twoantibiotics

TreatmentforHelicobacterpylori
infection
PPI+clarithromycin2x400mg+
metronidazole2x250mg(WTO)
PPI+amoxicillin2x1000mg+
clarithromycin2x500mg(OAC)or
PPI+amoxicillin3x500mg+
metronidazole3x400mg(whenpossible
resistancetoclarithromycin
Thedurationoftreatmentis7-10days

Treatment
quadrupletherapyconsistingof:
1gofamoxicillinx2/day,
500mgofmetronidazolex2/day,
20mgofomeprazolex2/dayand
120mgofbismuthsubcitratex3/day.
Thedurationoftreatmentis7-10days
IftestululmarkedC13respiratorisnegativeat6
weeksand3monthsaftertreatmentis
consideredtheeradicationofH.pyloriinfection

Surgerytherapy
Indicationsoperatorsremainduodenalulcercomplications:
-perforation,
-penetration,
-stenosisand
recurrentgastrointestinalbleedingoruncontrolleddrugs.
ItwasnotyetacceptedasinglesurgicalprocedureforUD.
Currentlysurgicalproceduresmostcommonlyusedare:
TruncalvagotomywithBilrothantrectomiewithanastomosistypeI(the
proximalduodenum)ortypeIIBilroth(gastro-jejunalanastomosis)process
withlowrateofrecurrence,butthehighestrateofpostoperative
complications
Vagotomywithpyloroplasty,especiallyyoungpeople,witharecurrenceof
theulcerinthefirst5yearsof5-8%.Vagotomymaybetronculatorselective
cuttingintoitonlyvagalbranchesthatinnervatethestomach.
vagotomywithantrectomy,andhasthelowestrateofcomplications.