消化内科课件消化性溃疡病英文课件pepticulcer

1、消化内科课件消化性溃疡病英文课件pepticulcer消化内科课件消化性溃疡病英文课件pepticulcerDefinition epidemiology 3. Etiology and pathogenesis 4. Clinical presentations5. Diagnosis6. Complications 7. TreatmentMain ContentsDefinition Main Contents1.Defenition of PUDPUD is Ulceration of gastrointestinal mucosa resulting from auto-digest

2、ion of gastric acid and pepsin.1.Defenition of PUDPUD is UlceStomach (gastric ulcer, GU)Duodenum (deodenal ucler, DU)esophagusGastro-jejunal anastomosis (post subtotal gastrectomy)Terminal ileum diverticulum（回肠末段憩室） (Meckels diverticulum，heterotopic gastric mucosa)Sites of peptic ulcerStomach (gastr

3、ic ulcer, GU)SitSites of peptic ulcerSites of peptic ulcerAnastomotic ulcerSites of peptic ulcerAnastomotic ulcerSites of peptSites of peptic ulcerSites of peptic ulcerDifference of ulcer and erosionUlcer is a mucosal defect that penetrates the muscularis mucosa（粘膜肌层）Erosion is a small, superficial

4、mucosal break that no more than the muscularis mucosa（粘膜肌层）Difference of ulcer and erosio2.EpidemiologyPrevalence rate about 10% overall lifetime The incidence of DU was higher than GUThe incidence of was male higher than femaleThe predominant age of DU is between 20 and 50 years old, whereas GU occ

5、urs in patients more than 40 years oldThe disease is more common in smokers2.EpidemiologyPrevalence rate 3. Etiology and pathogenesis 3. Etiology and pathogenesis Gastric Mucosa & Secretions The inside of the stomach is bathed in about 2 liters of gastric juice every dayGastric juice is composed of

6、digestive enzymes & concentrated hydrochloric acid, which can easily tear apart the toughest food or microorganismGastric Mucosa & Secretions Th12pathogenesis of PUD protective or defensive factors damaging or aggressive factorsAggressive factors increasing or the defensive factors decreasing will r

7、esult in mucosal damage, then lead to ulceration.14pathogenesis of PUD protectiPathogenesis of Ulcers Aggressive FactorsH. pylori NSAIDsGastric acid, pepsinBile saltsPancreatinSmoking and alcoholothersDefensive FactorsMucus-bicarbonate layer （粘液-碳酸氢盐）Mucosa（粘膜）Blood flow, cell renewalProstaglandinsG

8、rowth factorsPathogenesis of Ulcers AggressDefensive facors:1) Mucus-bicarbonate layer（粘液-HCO3-屏障）: Mucosal cells secreted mucus and HCO3-, which mixed and formed gel-like layer on mucosal surface. （粘膜细胞分泌的粘液和HCO3-，混合在一起覆盖于粘膜的表面形 成凝胶状的不流动层）2) mucosal barrier（粘膜屏障） Formed by tight junctions between m

9、ucosal epithelial cells. （粘膜上皮顶部的细胞膜及其细胞之间的紧密连接，称为粘膜屏障）Defensive facors:3) mucosal blood flow（粘膜血流） Provide oxygen and nutrients to Mucosa and submucosal tissues（给予粘膜和粘膜下组织供应氧和营养物质） Carry off H+ and metabolite in tissues （带走组织中的H+和代谢产物） Transport bicarbonate to mucosal surface for preventing excessi

10、ve acidification of mucosal cells. （向粘膜表面细胞输送HCO3- ，防止细胞过度酸化）3) mucosal blood flow（粘膜血流）16Mucus-bicarbonate layermucosal barriermucosal blood flow18Mucus-bicarbonate layermucos4) Prostaglandin E (PGE)Promote mucosal blood circulationpromote the secretion of bicarbonate(HCO3-)Promote DNA synthesis of

11、 mucosal cells5) cell factors: EGF(Epidermal Growth Factor) FGF(fibroblast Growth Factor ) TGF(transforming Growth Factor)important regulatory effect on mucosal wound repair4) Prostaglandin E (PGE) Etiology (Aggressive Factors)Helicobacter pylori (H. pylori) NSAIDs (non-steroidal anti-inflammatory d

12、rugs) Acid and pepsinOther risk factors: genetic predisposition, smoking, alcohol, stress, diet, virus infection Etiology HelicobacterEtiology H. pylori infectionSpiral shaped, flagellated, gram-negative bacillus （螺旋状，带有鞭毛，革兰氏阴性杆菌） Etiology H. pyH. Pylori:Colonizing in human stomachTransmitted from

13、person to person by oraloral or feco-oral spreadH. Pylori:Colonizing in human Nobel Prize 2005 “for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease Barry J. Marshall J. Robin Warren Nobel Prize 2005 “for their Most peptic ulcers associated with

14、 H. pylori infection90-100% of DU and 80-90% of GU are associated with H. Pylori infectionClinical Survey ProvementMost peptic ulcers associated 2. risk for development to peptic ulcers in patients with H. pylori infection is increased For the patients with H. pylori positive, about 15 to 20% will d

15、evelop to peptic ulcers in 10 yearsClinical Survey Provement2. risk for development to pepEradication of H. pylori is associated with higher healing ratesthe healing rate of peptic ulcerOnly eradication of H. pylori vs high effective acid suppressive therapy After eradication of H. pylori , refracto

16、ry ulcer can be healedClinical Survey EvidenceEradication of H. pylori is a4. Eradication ofH. pylori is associated with lower ulcer recurrence ratethe recurrence rate of peptic ulcer (per year):Clinical Survey Provementno treatment of H. pylori H. pylori eradication50-70%5%4. Eradication ofH. pylor

17、i iWhy H. pylori is one of the main causes of PUD?1. Most peptic ulcers associated with H. pylori infection2. risk for development to peptic ulcers in patients with H. pylori infection is increased 3. Eradication of H. pylori is associated with higher healing rates4. Eradication ofH. pylori is assoc

18、iated with lower ulcer recurrence rateWhy H. pylori is one of the mQuestion :The high acidity of the stomach kills many microorganisms. But how can H. pylori survive in high acid environment?Question :The high acidity of Why Hp can survive in the stomach (Hp 在胃内存活的原因) 1）Urease secreted by H. pylori

19、can hydrolysis urea to form ammonia and “ammonia clouds” around H. pylori, which neutralize or buffer gastric acid and protect H. pylori. （Hp产生的尿素酶水解尿素产生的氨在Hp周围形成“氨云”， 中和周围胃酸，从而保护Hp）Why Hp can survive in the stom2）The flagellum（鞭毛） make it motile, allowing it to live deep beneath the mucus layer （Hp

20、菌体呈螺旋形，一端有鞭毛，提供运动动力，使 其能寄居于最适部位）2）The flagellum（鞭毛） make it mo3) H. pylori can excrete adhesive factor, which make H. pylori adhere to gastric epithelium, then facilitate the toxins to damage gastric epithelial cells. (Hp存在粘附因子，它使Hp特异地粘附于胃粘膜，其 毒素作用上皮细胞)3) H. pylori can excrete adhes2. Hp damaged Def

21、ense and repair mechanism of gastric mucosa Hp损害粘膜的防御修复机制1) Vacuolating cytotoxin (VacA): the cells vacuoles 空泡毒素（VacA）蛋白：使细胞产生空泡2) Urease: damage mucosal directly or indirectly 尿素酶：直接或间接破坏粘膜屏障3) Mucus enzyme: degradate mucus, and promote H+ dispersion 粘液酶：降解粘液，促进H+反弥散4) Lipopolysaccharide, esterase

22、, and phospholipase: destruction of mucosal integrity. 脂多糖、酯酶、磷脂酶：破坏粘膜的完整性2. Hp damaged Defense and repa3. H. pylori stimulates excess secretion of gastrin hormone, which elevates acid secretion and thus increases aggressive factors.3. H. pylori stimulates excessEtiologyNon-Steroidal Anti-inflammato

23、ry Drugs (NSAIDS)Aspirin, Ibuprofen, Naproxen Risk factor: age, dose, duration of therapyPU:10 30%GU is more than DUcomplications are higher than general populationComplication: 15%EtiologyNon-Steroidal Anti-inf NSAIDs inhibit prostaglandin synthesis by blocking cyclooxygenase (COX)Pathogenesis of N

24、SAIDS NSAIDs inhibit prostaglandin COX-2 selective inhibitor (celecoxib) preferentially inhibit COX-2, and decrease the risk of NSAID-related ulceration.NSAIDsCOX-2 selective inhibitor (cAttention:Both NSAIDs and Helicobacter pyloriare the independent risk factors of peptic ulcer.（NSAIDs和幽门螺杆菌是引起消化性

25、溃疡的两个独立因素 ）Attention:EtiologyGastric acid and pepsin Pepsin is the direct factor which can damage gastric mucosa, but pepsin can be activated only when PH value less than 4 in stomachPU only occurs in position which contact with gastric acid Inhibition acid secretion can heal ulcerGastrinoma produce

26、 multiple, atypical, refractory ulcersPU wont occur when acid is completely lacking No acid, no ulcerEtiologyGastric acid and pepsiEtiology genetic predispositionGenetic susceptibility or intrafamilial H. pylori infectionThe concordance of peptic ulcer incidence in dizygotic twins higher than enzygo

27、tic twinsEtiology genetic predispositioEtiology Other risk factors: smoking, alcohol, stress, diet, virus infectionEtiology Other risk factors: SummaryPeptic ulcer is a multiple factors diseaseBoth Helicobacter pylori and NSAIDs are main causesImbalance between Mucosal aggressive factors and defensi

28、ve factorsNo acid, no ulceremphasis on the pathogenesis of GU and DU is differenceSummaryPeptic ulcer is a multiPathology（病理）Location: DU is always located in the anterior wall of duodenum, GU is always be found on the gastric angle andlesser curvature of gastric antrum （部位: DU多在球部前壁，GU多在胃角和胃窦小弯）Num

29、bers: single or multipleSize: DU15mm, GU20mm)Shape: round, oval, linear, irregular Pathology（病理）Location: DU is Clinical Manifestations Main symptoms: abdominal painProperties: dull, burning, swelling, sharpPosition: vagueOther dyspeptic symptoms: anorexia（厌食）, nausea, vomiting,bloating, belchingCli

30、nical Manifestations Main sCharacteristics of abdominal pain:1. Chronic, recurrent attacks（慢性过程，反复发作）2. periodic, remission phase is alternating with attacks. （发作呈周期性，与缓解期相互交替） 3. seasonal, occurs when autumn turns into winter or winter turns into spring（季节性，多在秋冬、冬春之交） 4. rhythmicity（发作时上腹痛呈节律性） 5.

31、acid suppression therapy is effective（抑酸治疗有效）Clinical Manifestations Characteristics of abdominal pRhythmicity GU: meal-pain-remissionaccentuated by eating DU: pain-meal-remissionhunger pain: manifests mostly before the meal, relieved by food nocturnal pain: wakes up patient at midnightRhythmicitySi

32、gns:Active peptic ulcer: fixed and limited tendernessAlleviated peptic ulcer: no obvious signsPhysical ExaminationSigns:Physical ExaminationSpecial Types of PUDPostbulbar duodenal ulcer（球后溃疡）Silence ulcer（无症状性溃疡）Pyloric channel ulcer（幽门管溃疡）Ulcer in elderly（老年人溃疡）Complex ulcers（复合溃疡）：GU+DURefractory

33、ulcer （难治性溃疡）Special Types of PUDPostbulbarDiagnosis of PUDHistory Endoscopy and biospyBarium RadiologyDiagnosis of PUDHistory Upper Endoscopythe most accurate test for PUDUpper Endoscopythe most accuraUpper EndoscopyRoutine biopsy can be used for exclude gastric carcinomaUpper EndoscopyRoutine biop

34、sy Upper EndoscopyEnsure if there is or no ulcer, site and stage of ulcer, the missed diagnosis rate is below 510%Biopsy can be used for distinguish benign and malignant ulcerMore reliable than the Barium Radiology for finding gastric body posterior wall ulcer（胃体后壁溃疡）and duodenal ulcer.Endoscopic he

35、mostasis（止血）Evaluation of therapeutic effectUpper EndoscopyEnsure if therBarium RadiologyDirect signs: niche（龛影）for establishing ulcer niche is outside stomach and duodenum Barium contour in Benign ulcer niche is inside stomach and duodenum Barium contour in malignant ulcer Indirect signs: just indi

36、cate ulcerLocal tenderness（局部压痛） incisura leading by spasm in gastric greater curvature（胃大弯痉挛切迹）bulbar deformity（球部变形）Barium RadiologyDirect signs: 52Barium Radiology54Barium RadiologyAdvantages: no painDisadvantages:(1) No ulcer in barium radiology can not ruled out ulcer completely (2) Can not be

37、used for Hp detection (3) Distinguishing between benign and malignant ulceris not reliableSelection principle:(1) No contraindication, preferred endoscopy(2) If patients cant afford, barium radiology is recommendBarium RadiologyAdvantages: no painBarium RadiDiagnosis of H. pylori InfectionNon-invasi

38、veC13 or C14 Urea Breath TestStool antigen testH. pylori IgG titer (serology)Invasive test (endoscopy)Rapid urease testHistological examinationMicrobial cultureDiagnosis of H. pylori InfectiDiagnosis of H. pylori: non-invasive1. C13 or C14 Urea Breath TestThe best non-invasive test for H. pylori inf

39、ection The preferred method for re-evaluationDiagnosis of H. pylori: non-inDiagnosis of H. pylori: non-invasive2. Serology TestSerum Antibodies (IgG) to H. pylori Not for active infection3. Stool antigen testFecal antigen of H. pylori possible alternative to urea testDiagnosis of H. pylori: non-inDi

40、agnosis of H. pylori: invasive1. Rapid urease testConsidered the endoscopic diagnostic test of choiceGastric biopsy specimens are placed in the test kit. If H pylori are present, bacterial urease converts urea to ammonia, which changes pH and produces a COLOR changeDiagnosis of H. pylori: invasiDiag

41、nosis of H. pylori: invasive2. Histological examinationH. Pylori on gastric epithelial cellsDiagnosis of H. pylori: invasiDiagnosis of H. pylori: invasive3. Microbial culture - Used in research studies and is not available routinely for clinical useDiagnosis of H. pylori: invasiDifferential Diagnosi

42、s of PUDFunctional dyspepsia - endoscopyBiliary or pancreatic diseases - ultrosonography, - MRCP, ERCPGastric cancerGastrinomas (Zollinger Ellison syndrome) Differential Diagnosis of PUDFDifferential Diagnosis:Benign gastric ulcer - smooth, regular, rounded edges, - flat, smooth ulcer baseGastric ca

43、ncer - ulcerated mass - nodular, clubbed, - fused surrounding folds - irregular or thickened marginsDifferential Diagnosis:Benign Multiple biopsies optimal number of biopsies first biopsy- correct diagnosis in 70% four biopsy 95%Seven biopsy 98%Follow-up endoscopyDifferentiation: gastric ulcer vs. c

44、ancerMultiple biopsies DifferentiatDifferential Diagnosis:Gastrinomas (Zollinger-Ellison syndrome)non-beta islet cell tumor of the pancreas leading to massive production of gastrin and excessive secretion of gastric acid Differential Diagnosis:non-betmultiple & refractory ulcers in unusual locations

45、often companied with diarrhea Gastric secretory test - Basic acid output 15mEq/hour Fasting serum gastrin 500pg/ml Ultrosonography, CTGastrinomas (Zollinger-Ellison syndrome)multiple & refractory ulcers iComplications of PUDCommon:HemorrhagePerforationoutlet Stenosis or pyloric obstructionMalignant

46、TransformationComplications of PUDCommon:1. Hemorrhagethe most common complicationIt occurs when the ulcer erodes one of the blood vessels1. Hemorrhagethe most common cclinical featuresmay appear as hematemesis or bloody vomitus, or the blood may appear in stools, where it gives the stools a dark, t

47、arry appearance, which is referred to as melenaSevere hemorrhage may lead to shockhematemesisclinical featuresmay appear astreatment - Routine medical therapy - Emergency endoscopy to stop bleeding - Surgerytreatment - Routine medical th69 Forrest typing of peptic ulcer bleeding （消化性溃疡出血的Forrest分型）7

48、1 Forrest typing of peptic ul2. Perforation :An ulcer can break through the entire gastro-intestinal wallBacteria and partially digested fool spill into peritoneum=peritonitis2. Perforation :An ulcer can bclinical featuresThe first sign is often sudden intense abdominal painSigns of acute peritoniti

49、sBoard like rigidity of abdomenclinical featuresThe first sigX-ray may reveal free gas under the diaphragm 消化内科课件消化性溃疡病英文课件pepticulcertreatmentSurgery is required immediatelytreatmentSurgery is required i3. Stenosis Scarring and swelling due to ulcers causes narrowing in the duodenum and gastric out

50、let obstructionGastric outlet obstruction3. Stenosis Scarring and swell clinical featuresRecurrent, large-volume vomiting, unpleasant in nature, totally lacking in bile, containing foodstuff taken several days previously clinical featuresRecurrent, l4. Malignant Transformation:DU generally benignGU

51、with possibility of malignancyBiopsy is very important4. Malignant Transformation:DUTreatment Lifestyle changes Medications Surgical interventionTreatment Lifestyle changes1.Life-style ModificationRegular lifestyle, rest, relaxationDiet: Regular mealsbland diet（清淡饮食）: avoid spices, coffee, alcohol,

52、or diets rich in milk and cream Smoking cessationNSAIDs discontinuation if possible1.Life-style ModificationRegul2.Medications Acid suppressionEradication of H. pyloriMucosal Protectants2.Medications Acid suppressionAcid Suppression 1. Proton pump inhibitors (PPIs)2. H2-recptor antagonists (H2RAs) N

53、o acid, no ulcer!Acid Suppression 1. Proton pumProton Pump Inhibitors (PPIs) Mechanism of actionUncompetitive and irreversible inhibition of proton pump (H+/ K+-ATPase) that is responsible for final step in gastric acid secretion from the parietal cell.Most effective drugs in acid suppression, inhib

54、iting over 90% of 24-hour acid secretionPPIs include: Omeprazole, Lansoprazole, Pantoprazole Rabeprazole, EsomeprazoleProton Pump Inhibitors (PPIs) Mechanism of actionCompetitively and reversibly block to histamine H2 receptors on the parietal cells thus reduce gastric secretionLess potent than PPIs

55、H2RAs include:Cimetidine, Ranitidine, Famotidine, NizatidineH2-recptor Antagonists (H2RAs)Mechanism of actionH2RAs incluEradication of H. pylori :H. pylori is sensitive to the following antibiotics:Amoxicillin（阿莫西林）Tetracyclin（四环素）Clarithromycin（克拉霉素）Metronidazole（甲硝唑）Therapy with one or two drugs i

56、s ineffectiveCombined therapy is usually used - Eradication of H. pylori :H. pEradication of H. pyloriThe standard first-line therapy is triple therapy” - PPI or bismuth+ two antibioticsquadruple therapy: PPI + bismuth+ two antibiotics course of treatment is 10 or 14 daysEradication of H. pyloriThe

57、st Eradicate H. pylori infectionPPI and Bismuth TwoAntibiotics +Clarithromycin 500mg bidAmoxicillin 1000mg bid(Tetracycline) 750mg bidMetronidazole 400mg bidFurazolidone 100mg bidQuadruple therapy, for 10 or 14 daysOmeprazole 20mg bidLansoprazole 30mg bidPantoprazole 40mg bidRabeprazole 10mg bidEsom

58、eprazole 20mg bid Eradicate H. pylori infectionTreatment course of peptic ulcerTotal couse for GU:6-8 weeks Total course for DU：4-6 weeksAttention: treatment course for PU course for eradicating HPTreatment course of peptic ulMucosal Protective AgentsSucralfate（硫糖铝）Misoprostol（米索前列醇）Colloidal Bismut

59、h compounds（胶体铋化合物）Mucosal Protective AgentsSucraSucralfate:Coats ulcer at low pH, thus promoting healingThe main side effect is constipationSucralfate:Colloidal Bismuth compoundsIt forms a precipitate with mucous cover the ulcer with a protective coat that prevent effect of HClPromote healing of ul

60、cerBactericidal effect against H. pylori Colloidal Bismuth compoundsMisoprostolProstaglandin analogsShould be particularly effective at healing NSAID induced ulcersFrequently causes diarrhea and uterine contraction（子宫收缩）MisoprostolGeneral StrategyDetermine the etiology of ulcerEradicate H. pylori in