Acid Related DisordersAcid Related DisordersM. Amer Khatib, MDAssistant Professor in Medicine and GastroenterologyUniversity of Jordan Acid Related DisordersAcid Related DisordersPetic !lcer disease "PUD#$Gastric Ulcers "GU#$D!odenal Ulcers "DU#Gastro %sohageal Refl!& Disease "G%RD# Petic Ulcer Disease "PUD#Petic Ulcer Disease "PUD#Definition'$Defects in the gastrointestinal m!cosa that e&tend thro!gh the m!sc!laris m!cosae PUD is an imortant ca!se of morbidity and health care costs estimates of e&endit!res related to (or) loss, hositali*ation, and o!tatient care "e&cl!ding medication costs# are +,.-, billion er year in the United .tates./01 of Americans are s!ffering from PUD. PUDPUD2linical Presentation2linical PresentationDysesia$DU' 3he 4classic4 symtoms occ!r (hen acid is secreted in the absence of a food b!ffer. symtoms occ!r t(o to five ho!rs after meals or on an emty stomach. .ymtoms also occ!r at night, bet(een // PM and 5 AM, (hen the circadian stim!lation of acid secretion is ma&imal. $GU' 6as classically been associated (ith more severe ain occ!rring soon after meals, (ith less fre7!ent relief by antacids or food. Postrandial belching8loating%igastric f!llnessAnore&ia%arly satiety9a!sea and occasional vomitingPUDPUD2linical Presentation2linical Presentation.ilent Ulcers in /:5; of asymtomatic o!lation 5< ; of comlicated !lcers resent (itho!t symtomsmore fre7!ent in elderly atients and individ!als cons!ming nonsteroidal antiinflammatory dr!gs "9.A=Ds# Penetrating !lcers'$a shift from the tyical vag!e visceral discomfort to a more locali*ed and intense ain that radiates to the bac) and is not relieved by food or antacids. Perforation'$s!dden develoment of severe, diff!se abdominal ain. Pyloric o!tlet obstr!ction'$ >omiting is the cardinal feat!re resent in most cases.6emorrhage'$ may be heralded by na!sea, hematemesis, melena, or di**iness.Presentation of more comlicated cases PathohysiologyPathohysiology PUDPUD2a!ses2a!ses6 Pylori9onsteroidal antiinflammatory dr!gsGastric acid hyersecretion?amilial aggregation PUDPUD2a!ses2a!ses6 Pylori9onsteroidal antiinflammatory dr!gs 9onsteroidal antiinflammatory dr!gsGastric acid hyersecretion Gastric acid hyersecretion?amilial aggregation ?amilial aggregation .iral:shaed, gram:negative bacteri!m (ith fo!r to si& !niolar sheathed flagella. 3he organism (as first named 2amylobacter:li)e "c!rved rod# organism, then 2amylobacter ylori. =ts name (as later changed to 6. ylori. =ts helical shae and flagella, assist its movement thro!gh the gastric m!c!s layer.6elicobacter ylori6elicobacter ylori Prevalence of 6. Pylori in etic !lcerPrevalence of 6. Pylori in etic !lcer@2oyright .cience Press =nternet .ervices H. pylori coloni*e the h!man gastric m!c!s layer thro!gh a combination of flagellae mediated motility and adherence to carbohydrate recetor str!ct!re, in order to avoid clearance by the shedding of cells and m!c!s. 8y secretion of the vac!olating cytoto&in, the microbes can !tili*e the cell as a so!rce of n!trition. 6o(ever, s!ch dist!rbances (ill also recr!it (hite blod cells, a sit!ation that event!ally res!lts in a state of chronic inflammation. Ance the microbes have gained eno!gh of n!trients, they (ill ret!rn to the rotective m!c!s layer, and by doing so, they (ill escae the PM9:cells. 3here is s!bse7!ently an e7!illibri!m rocess in bet(een adhering and Bfree:floatingC microbes, (here the rocess is driven by arameters s!ch as adherence roerties, to&in secretion, metabolic efficacy and robably many additional still !nrecogni*ed factors. Antral 6. Pylori infectionGenetic redisostionDecrease antral somatostatinDecrease m!cosal defense=ncreased inflammatory cells and cyto)inesUlcer formation=ncrease acid o!t!tGastric metalasia and coloni*ationD!odenitis%nvironmental factors=ncrease arietal cell mass and sensitivity=ncrease Gastrin release PUDPUD2a!ses2a!ses6 Pylori 6 Pylori9onsteroidal antiinflammatory dr!gsGastric acid hyersecretion?amilial aggregation PUDPUD2a!ses2a!ses6 Pylori 6 Pylori9onsteroidal antiinflammatory dr!gsGastric acid hyersecretion Gastric acid hyersecretion?amilial aggregation ?amilial aggregationRis) of !lcer formation from 9.A=DDs' =ncrease (ith =ncreasing age, artic!larly E-< 6igher 9.A=D dose Past history of gastrod!odenal to&icity from 9.A=Ds or etic !lcer disease 2onc!rrent !se of gl!cocorticoids, anticoag!lants, bishoshonates, or other 9.A=Ds 9.A=Ds inhibit the 2AF en*yme, (hiche&ists in t(o formsArachidonic acid2AF:/"constit!tive#2AF:5"ind!ced by inflammatory stim!li#9on:selective 9.A=Ds =nflammation Pain ?everProstaglandins Prostaglandins2AF:5 selective 9.A=DsAdated from >ane G 8otting /HH, Gastrointestinal cytorotection Platelet activity 9.A=Ds.ystemic effects of 9.A=Ds may lead to gastric m!cosal damageAltered inflammatorymediator rod!ction"e.g. decreased rostaglandin, increased t!mo!r necrosis factor#=ncreased ne!trohil$endothelial adhesion2aillary obstr!ction 9e!trohil release ofroteases and o&ygen:derived free radicals=schaemic0hyo&ic cell inI!ry%ndothelial and eithelial inI!ryM!cosal !lcerationJallace /HHK PUDPUD2a!ses2a!ses6 Pylori 6 Pylori9onsteroidal antiinflammatory dr!gs 9onsteroidal antiinflammatory dr!gsGastric acid hyersecretion Lollinger:%llison syndrome?amilial aggregation ?amilial aggregationDU and no 6elicobacter ylori resentPresence of diarrhea?ail!re of the !lcer to heal (ith 6. ylori eradication M!ltile !lcers or !lcers in !n!s!al locations .evere etic !lcer disease leading to a comlication "eg, bleeding erforation, intractability# .evere or resistant etic esohageal disease 6istory of nehrolithiasis or endocrinoathies ?amily history of nehrolithiasis, endocrinoathies, or etic !lcer disease PUDPUD2a!ses2a!ses6 Pylori 6 Pylori9onsteroidal antiinflammatory dr!gs 9onsteroidal antiinflammatory dr!gsGastric acid hyersecretion Gastric acid hyersecretion?amilial aggregation ?irst:degree relatives of atients (ith DU have a threefold increase in the revalence of DU b!t not GU Relatives of atients (ith GU have a threefold increase in the revalence of GU b!t not DU.6yeresinogenemia (as roosed as a mar)er of a!tosomal dominant inheritance. ?actors that infl!ence the co!rse of etic !lcer?actors that infl!ence the co!rse of etic !lcer.mo)ingAlcoholDiet Psychologic factors DiagnosisDiagnosis8ari!m st!dies%ndoscoy.erological test 8ari!m .t!dy8ari!m .t!dy8ari!m (ithin an !lcer niche, (hich is generally ro!nd or oval ?olds radiating to the crater and deformities in the region secondary to sasm, edema, and scarring 8ari!m .t!dy8ari!m .t!dy.ensitivity$.ingle contrast,