消化性溃疡

消化性溃疡Pepticulcer学时安排及重点内容重点内容PU发病机理：胃酸、HpPU临床表现：症状、内镜PU药物治疗:PPI、原则学时:3h胃溃疡大体标本基本概念胃溃疡（Gastriculcer）胃角、胃窦、胃体、贲门、幽门管十二指肠溃疡（Duodenalulcer）球部、球后胃底胃体胃窦贲门角切迹十二指肠胃小弯胃大弯“胃溃疡”PU的分类DUGUCUH.pyloriNSAIDs应激遗传其他部位病因容易混淆的概念糜烂≠溃疡（黏膜基层）复合性溃疡（Complexulcer）多发性溃疡（Multipleulcer）对吻溃疡（Kissulcer）发病率10～12％Age:20～50MF（6:1）DUGU（3:1）SeasonPU发生机理防御因子－攻击因子失衡幽门螺杆菌感染胃肠运动功能障碍易感因素正常胃粘膜防御因子胃粘液－HCO3-屏障胃粘液、粘液内pH梯度细胞屏障：细胞膜及紧密连接胃粘膜屏障细胞再生胃粘膜血流量（GMBF）胃肠道激素Gastrin，CCK，Somatostatin，VIP，NO胃液胃粘液层粘液颗粒上皮细胞胃粘膜屏障攻击因子胃酸（H+）胃蛋白酶NSAIDs胆汁反流幽门螺杆菌胃黏膜细胞组成上皮细胞壁细胞（parietalcell）主细胞（chiefcell）G细胞ECL细胞黏液H+PrepepsinGastrin组织胺主细胞壁细胞胃酸分泌增多的原因壁细胞总数增多：parietalcellmass（PCM）壁细胞敏感性增强反馈机制缺陷迷走神经张力增高有效的镇痛及抗炎药物世界范围内广泛应用每年超过10亿张处方非处方用药（OTC）每年消耗20亿美元以上肌肉骨骼疾病冠心病NonsteroidalAnti-inflammatoryDrugsFosslienE.AnnClinLabSci1998NSAIDs损伤机理局部刺激（H+）抑制COX-1活性细胞保护性PGs5－脂肪酶途径O自由基NSAID-associatedulcerformation十二指肠液反流胃窦十二指肠协调性下降排空延缓↓Gastrin↑↓H+↑溃疡碱性十二指肠内容物反流至胃Helicobacterpylori,HpScience2005,310(5745):34幽门螺杆菌感染1983.Warren,Marshall首次培养成功Campylobacterpylori,CP1990.Helicobacterpylori,Hp(Sydney)HpPU?1994.Hppepticulcer,chronicgastitis,gastriccancer,MALTlymphoma(LosAngeles)1998.Hp+,PU,CGHp根除治疗幽门螺杆菌示意图Hp的地理分布Hp与PU、胃炎及胃癌密切相关Hp的致病因子鞭毛黏附素尿素酶（Urease）VacA（致空泡变性细胞毒素）CagA（细胞毒素相关蛋白）脂多糖NH2O=C+H2O2NH3+CO2NH2+H+NH4+尿素酶（Urease）UreaseGastrin↑pH↑Hp的主要致病因子CagAVacACagPAIVacA的空泡毒性Hp致溃疡机理StudiesonCagA&VacATheprevalenceofCagAishigh(90%)inH.pyloriinChinaBacteriawithCagAandVacApositiveiseasiertocausepepticulcerThetoxicitycanbetestedbyasimpleserumantibody-basedmethodDuY,LiZS,etal.1998Hp致溃疡机理胃泌素分泌增加泌酸增加上皮细胞分泌IL-1,胃粘膜中性IL-2,IL-8及TNF粒细胞浸润VacA、CagA上皮细胞损伤Hp感染尿素酶产氨胃粘膜屏障破坏PU“漏屋”学说H.pylori慢性胃炎消化性溃疡胃癌MALT淋巴瘤Hp与消化性溃疡NoHp,NoAcid,NoUlcer!!NoAcid,NoUlcer!H+Pepsin防御H+PepsinH+Pepsin防御H+PepsinDuodenalulcerH+Pepsin防御H+Pepsin防御Gastriculcer易感因素遗传因素（O型血）饮食因素身心因素（情绪应激）吸烟病理病理特征-----慢性溃疡部位DU：球部前壁GU：胃角、胃窦小弯组织学特征①炎性渗出、坏死组织、纤维蛋白②炎细胞浸润层③肉芽组织④纤维疤痕组织溃疡的病理描述数目大小GU：0.5～2.5cmDU：0.2～1.5cm2.5cm：巨大溃疡形状：圆形、类圆、线形、不规则形深度：浅－粘膜层深－全层（穿透性溃疡）症状上腹痛其他症状：腹胀、反酸、嗳气等体征缓解期：无明显体征发作期：上腹部压痛临床表现部位：中上腹、剑突下性质：钝痛、灼痛、胀痛、隐痛慢性节律性DU：餐后2~4h（饥饿痛、夜间痛）GU：餐后1/2~1h周期性/季节性腹痛的特点特殊类型的溃疡无症状溃疡老年、小儿溃疡幽门管溃疡球后溃疡吻合口溃疡实验室及辅助检查Hp检测大便潜血胃液分析胃内24小时pH监测胃泌素测定侵入性胃粘膜Hp培养涂片染色尿素酶试验PCR非侵入性血清Hp抗体检测13C/14C-UBTHp的检测方法13C-尿素呼气试验Hp的临床诊断标准下列二项中任一项阳性者，则诊断Hp感染Hp形态学（涂片或组织学染色）尿素酶依赖性试验（RUT、13C或14C-UBT）X线检查阳性率：80～90%直接征象：龛影间接征象GU：痉挛性切迹、幽门痉挛、激惹现象、局部压痛DU：畸形、花瓣样PU内镜表现Endoscopy优点观察PU形态、大小、形状、部位判断其病期（活动、愈合、疤痕）可作活检，鉴别良、恶性作Hp检测随访PU的内镜分期活动期（ActiveStage1，2）愈合期（HealingStage1，2）疤痕期（ScarStage1，2）胃体胃窦十二指肠胃底NormalviewofstomachGUatbody-antrumjointA1A2GUatbody-antrumjointH1H2GUatbody-antrumjointS1S2GUatantrumNSAIDs-associatedGUBenignandmalignantGUbenignmalignancyDUatanteriorwallA1A2DUatanteriorwallH1H2DUatanteriorwallS1S2DUwithhemorrhageDarkbloodclotUlcerwithactivebleeding内镜下胃溃疡注射止血治疗诊断及鉴别诊断诊断依据典型病史：慢性、节律性、周期性上腹部隐痛，局部压痛等确诊：X线钡餐及内镜检查DifferencesbetweenGU&DUGUDULesionSuperficial;smoothmargins;round,oval,orcone-shaped.PenetratingLocationPredominantlyantrum,alsoinbodyandfundusofStomach.First1-2cmofduodenumGastricsecretionNormalordecreased.Increased.Incidence①Greaterinwomen.②Peakage50~60yr.③Morecommoninpersonsoflowersocioeconomicstatus.④Increasedwithsmoking,drug,andalcoholuse.⑤Increasedwithincompetentpyloricsphincter.⑥Increasedwithstressulcersaftersevereburns,headtrauma,andmajorsurgery.①Greaterinmen.②Peakage35-45yr.③Associatedwithpsychologicstress.④Increasedwithsmoking,drug,andalcoholuse.⑤Associatedwithotherdiseases(e.g.,chronicobstructivepulmonarydisease,pancreaticdisease,hyperparathyroidism,Zollinger-Ellisonsyndrome,chronicrenalfailure).胃癌慢性胃炎非溃疡性消化不良胃泌素瘤（卓-艾综合征）十二指肠炎胆囊炎、胆石症鉴别诊断oesophagealulcerAholeintheliningoftheoesophaguscorrodedbytheacidicdigestivejuicessecretedbythestomachcells.Age30,M:F=3:1UlcerformationisrelatedtoH.pyloribacteriainthestomach,anti-inflammatorymedications,andsmokingcigarettes.Ulcerpainmaynotcorrelatewiththepresenceorseverityofulceration.Diagnosisismadewithbariumendoscopy.Complicationsofulcersincludebleedingandperforation.ComplexulcerSimultaneouslyoccurinstomachandduodenum(GU+DU)5%inPUEasiertocauseobstructionRaremalignancyUlcerofpyloriccanalWithin2cmareafrompylorusSimilartoDU,HighacidPost-mealpainMorecomplicationsPostbulbarulcer1%~3%ofDuM:F=11~16:1Age:29~49WithDUcharactersWithintheproximal2cmofthedescendingduodenumabovetheampullaofVaterPainatnight,backpainBleedingZollinger-EllisonSyndrome卓-艾氏综合征（ZES）Gastrintumorsinthepancreasandduodenum,ulcersinthestomachandduodenum.Thetumorssecreteahormonecalledgastrinthatcausesthestomachtoproducetoomuchacid,whichinturncausesstomachandduodenalulcers(pepticulcers).Approximately25percentofZEScasesareassociatedwithageneticdisordercalledmultipleendocrineneoplasiatype1Symptoms:includesignsofpepticulcers:burningpainintheabdomen;diarrhea;nausea;vomiting;fatigue;weakness;weightloss;andbleeding.Diagnosis:serumgastrin↑.BAO15mmol/h,MAO60mmol/h,BAO/MAO0.6Treatment:PPI,refractory,surgeryStomalulcerOccurredinthepost-operationstomachM:F=7.9:1PainBleeding,perforation并发症大出血（bleeding）幽门梗阻（pyloricobstruction）穿孔（perforation）癌变（carcinomatouschange）PU转归梗阻愈合癌变出血穿孔PU的治疗治疗原则近期目标：解除症状，促进溃疡愈合远期目标：Hp