1、Department of GastroenterologyTongji HospitalDan zilil Peptic ulcer (PU) is refered to a group of ulcerative disorders of the upper gastrointestinal tract, involving principally the most proximal portion (the bulb or second portion) of the duodenum and the stomach, which have in common participation
2、 of acid-pepsin in their pathogenesis. lThe major forms are duodenal ulcer (DU) and gastric ulcer (GU). lThe injury penetrates at least through the mucosa, submucosa and muscularis mucosa and so, differs from an erosion, in which only the mucosal surface is disrupted.lIt is a common condition - ther
3、e is a lifetime incidence of up to 10%.lReportedly lower incidence in lower socio-economic groups lThere is an increased frequency of new ulcers and recurrences during certain seasons, especially during autumn and winter months. lFour times more common in men than womenlMost common in young and midd
4、le age - peak 20-40 yearslStrong genetic influence: three times more common in first degree relatives of patients with an ulcer than in the general population more common in patients with blood group O increased incidence in white males with HLA-B5 antigen associated with increased serum pepsinogenl
5、Smoking is twice as common in patients with PUlH. pylori infection is often seen ( over 95%)lCommon condition in late middle age - incidence increases with agelAbout twice as common in males than in females lMore common in patients with blood group A lUse of NSAIDs - three- to four-fold increase in
6、risk of GUlLess related to HP than DU (70% to over 95%)lHelicobacter Pylori (HP) infection :60-80%lUse of NSAIDslGastric hypersecretion and pepsinlGenetic predisposition lDisorder of the gastric or duodenal motilitylStress and psychologic factorslCigarette smokinglDietary influenceslHypercalcaemia l
7、Renal failure AcidAcid、PepsinPepsinNASAIDsNASAIDsAlcoholAlcoholSmokingSmokingH. pyloriH. pyloriInflammationInflammationFree radicalsFree radicalsMucosal barrierMucosal barrierMucus-bicarbonate Mucus-bicarbonate barrierbarrierPhosopholipidsPhosopholipidsMucosal blood flowMucosal blood flowCell restit
8、utionCell restitutionProstaglandinsProstaglandinsEGFEGF Aggressive factors Defensive factorsAggressive factors Defensive factors With peptic ulcer,the balance between aggressive With peptic ulcer,the balance between aggressive and defensive factors is disturbedand defensive factors is disturbed lThe
9、 pathogenesis of DU does mainly correlate with the reinforcement of aggressive factors (oversecretion of acid). .lThe pathogenesis of GU is closely linked to an impairment of mucosal protection. lThe HP infection is particularly important in the development of DU and gastritis. lThere is a high inci
10、dence of HP infection in patients with PU: DU over 95 %, GU 70 %.lThe eradication of HP may accelerate the healing of ulcer and markedly decrease the recurrence of ulcer.lHP infection may change the balance between aggressive and defensive factors. HP infection damage the defensive factors and enhan
11、ce the aggressive factorslDamage mucosal barrier Cytotoxin: VacA、CagA. The cagA is associated with the stimulation of interleukin-8 by the host. IL-8 is a strongly pro-inflammatory cytokine that attracts polymorphs to the mucosa. Vacuolating cytotoxin (空泡毒素空泡毒素) has a direct toxic effect on epitheli
12、al cells. Urease enzyme: It may have a direct inflammatory effect on the gastric mucosa. Mucus enzyme, Phospholipase A, hemolysin:lInflammatory reaction: HP invades the mucosa and activates the inflammatory cells or functions through inflammatory cytokine.lImmune reaction:lHP infection causes hyperg
13、astrinemia: increase the secretion of acid and pepsin.l幽门螺杆菌宿主环境因素lHP感染慢性胃窦炎十二指肠球部酸负荷胃上皮化生胆酸沉淀幽门螺杆菌十二指肠球部定植十二指肠炎症粘膜防御和修复受损胃酸/胃蛋白酶 DU lHP胃粘膜炎症屏障功能受损GU lNSAIDs are associated with an increased risk of GU. There is no proven relationship between the formation of DU and the use of NSAIDslThe predisposit
14、ion seems to be mediated through an alteration in gastric mucosal potentials and in prostaglandin synthesis (inhibit COX).lThe formation of PU is due to the self-digestion of gastric acid and pepsin, and acid is determinant factor.lCertain physiologic alternations have been identified in people with
15、 DU. These include:lA twofold increase in the number of gastric parietal cellslAn increase in basal and stimulated acid and pepsin productionlAn increase in gastric acid secretion in response to a protein meallAn increase in the rate of gastric emptying which may expose duodenal mucosa to a higher h
16、ydrogen-ion concentrationlA reduction in the suppression of gastrin release by an acid stimulusThis may reflect a defect in feedback inhibition and may predispose to prolonged acid productionlPeople with blood type O are more likely to develop DU.lThere is an increased incidence of GU in people with
17、 blood type A.lThere is an increased incidence of PU in first-degree relatives.lAn increase in the rate of gastric emptying in duodenal ulcer may increase the acid load and the damage of duodenal mucosa lDelayed gastric emptying in gastric ulcer may stimulate the gastrin secretion of G cells and inc
18、rease the gastric acid secretion.lBile reflux with pyloric sphincter incompetence can damage gastric mucosa and is related to the formation of GU.lStress and psychologic factors could affect the gastric acid secretion, the gastric or duodenal motility and mucosal blood flow, then cause the formation
19、 of ulcer.lCigarette smoking: to cause an increase in the incidence of PU, a decrease in the healing rate, and an increase in the recurrence rate.lFoodstuffs, coffee, or alcohol have not been linked to the development of PU.lThe role of glucocorticoids in ulcer development remains controversial. Glu
20、cocorticoids, at moderate doses, show no increased risk of ulcer. With cumulative doses greater than 1 g or prolonged therapy for longer than 1 month, there may be some increased incidence.lAssociated diseases: with an increased incidence of DU. These include:v Chronic obstructive pulmonary diseasev
21、Hepatic cirrhosisvChronic renal failure, especially after kidney transplantation or on hemodialysisvCrohn diseasevChronic pancreatitisvhypercalcaemiaGenetic predisposition H.pylori(HP) infection NSAID Acid-peptic Chronic Gastric Barrier Secretion gastritis ulcer breakdown Delayed Bile reflux gastric
22、 emptying Gastric metaplasia HP HP Duodenum colonization migration Metaplasia Duodenitis Duodenal ulcer多因素多因素幽门螺杆菌幽门螺杆菌NSAIDNSAID失平衡失平衡胃酸胃酸l部位：DU 95%球部，少数球后部（球后溃疡）；GU 85%胃窦小弯、胃角。l圆形或椭圆形，多数直径2.5cm，深度1.0cm；溃疡累及粘膜肌层以下；可出血、穿孔。l修复愈合，一般48周，疤痕收缩或粘连可致梗阻。l同一部位有2个以上的溃疡称为多发性溃疡。胃、十二指肠同时有溃疡称为复合性溃疡。Character: a.
23、chronic and recurrent b. periodic attacks c. regular epigastric pain d. seasonal, precipitating factor lThe clinical presentation of PU is variable.lIt may be asymptomatic, cause abdominal discomfort or abdominal pain.lThe most usual symptom is localized epigastric pain, described as sharp, burning
24、or gnawing, or may be perceived as abdominal pressure or fullness, or as a hunger sensation. lpain - epigastric; radiates to the back; onset 1 to 3 hours after eating, often worse at night or in the early morning hours. lrelieved by eating and drinking milk or antacids.lprecipitating factors include
25、 missing a meal, anxiety or stress. lnocturnal pain is a feature of DU, it frequently awakens the patients at night.lThe pain of GU may vary from a vague and mild discomfort, which is ignored, to a very severe pain that makes the patient lie down.lThe pain occurs 15 to 30 minutes after eatinglThe pa
26、in is relieved by vomiting and made worse by eating, and relief by antacids is less consistent than DU. The pain often worst during the day and the nocturnal pain occurs less than that of DU.l疼痛部位： GU剑突下正中或偏左 DU上腹正中或偏右l疼痛性质： 多为灼痛，亦可为钝痛、胀痛、剧痛或饥饿样不适感 l疼痛范围一般如手掌面积大小，轻至中度持续性痛。l疼痛节律性： DU进食疼痛缓解疼痛（多为空腹痛、可伴
27、有夜间疼痛） GU进食疼痛缓解（多为餐后痛，一小时左右发作，胃排空缓解）lNausea, Vomiting lAnorexia, weight losslDyspepsia, including belching, bloating, distention, fatty food intolerance, fullness in the upper part of the abdomenlEructation, sour regurgitationlHeartburn, chest discomfort or painlHematemesis or melena resulting from
28、gastrointestinal bleeding. lMany patients with active PU have no ulcer symptoms.lChanges in the character of ulcer pain may signal the development of complications.lFor example, ulcer pain which becomes constant, is longer relieved by food or antacids, or radiated to the back or to either upper quad
29、rant may herald penetration of the ulcer (often posteriorly into the pancreas). lAbrupt, severe, or generalized abdominal pain is characteristic of free ulcer perforation into the peritoneal cavity. lIn uncomplicated PU disease, clinical findings are few and nonspecific. lThe most common finding is
30、epigastric tenderness.lThe presence of complications: Succussion splash resulting from partial or complete gastric outlet obstruction.Signs of acute abdomen resulting from perforation.lPyloric Channel Ulcers: to vomit frequently and to have pain occurring shortly after eating that is poorly relieved
31、 by antacids. It is often complicated by gastric outlet obstruction, hemorrhage and perforation. The effect of medical treatment is poor. lPostbullbar Ulcers: The ulcers occur on the postbulbar portion of the duodenum . Although the pain is more likely to be severe, its characteristics are similar t
32、o those of pain associated with a bulbar ulcer. Postbulbar ulcers are reputedly also more often complicated by bleeding or obstruction. lGiant ulcers: Most ulcers are less than 1cm in diameter, an ulcer crater measuring more than 2cm is considered “giant” in size. Giant GU often occurs on the poster
33、ior wall. The upper abdominal pain of the presenting attack often is associated with back radiation because of posterior penetration. Bleeding frequently occurs with giant ulcers. lComplex ulcer: GU and DU simultaneously exist. There is a high incidence of pyloric channel obstruction.lSilence ulcer:
34、 15-35% of patients (especially in elder patients) with active PU have no ulcer symptoms. 50%NSAIDs ulcer no symptomslPeptic ulcer in elder patients: there is an increased incidence in recently years. The symptoms generally are not typical. Upper parts ulcer of gastric corpus and giant ulcers are co
35、mmon.lMeasurement of acid secretion is not useful in the routine evaluation of PUD. lAcid-output studies (A secretin stimulation test) can be performed to distinguish Zollinger-Ellison syndrome from other conditions with a high serum gastrin, such as achlorhydria（胃（胃酸缺乏）酸缺乏）and antisecretory therapy
36、 with a proton pump inhibitor (PPI). lSerum gastrin levels is useful in patients with recurrent, refractory, or complicated PUD and in patients with a family history of PUD to screen for Z-E syndrome. lTests for HP：very important, the HP tests should be routinely performed before and after anti-HP t
37、herapy.非侵入性检查非侵入性检查：不依赖内镜检查，包括：不依赖内镜检查，包括:l14C or 13C-urea breath tests (UBT)l15尿氨排泄试验尿氨排泄试验l粪便粪便Hp抗原检测抗原检测 (HpSA) l血清及分泌物（唾液、尿液等）抗体检测血清及分泌物（唾液、尿液等）抗体检测l基因芯片和蛋白芯片检测基因芯片和蛋白芯片检测等等 病人依从性较好。病人依从性较好。侵入性检查：侵入性检查：依赖于胃镜活检，包括：依赖于胃镜活检，包括：lRapid urease test 快速尿素酶试验快速尿素酶试验(RUT)l胃黏膜直接涂片染色镜检胃黏膜直接涂片染色镜检l胃黏膜组织切片染色镜
38、检（如胃黏膜组织切片染色镜检（如W-S银染、银染、改良改良Giemsa染色、甲苯胺蓝染色、免疫染色、甲苯胺蓝染色、免疫 组化染色）组化染色）lCulturel基因检测方法基因检测方法 (如如PCR等等)l免疫检测尿素酶免疫检测尿素酶(IRUT) lFecal occult blood: If bleeding has occurred, stools may contain gross or occult blood. The fecal occult blood generally is intermitent positive.lIn most patients with typical
39、symptoms, the physician will suspect PU initially and will institute appropriate diagnostic procedures without delay.lHowever, not all patients present with typical symptoms, and a high index of suspicion must be maintained when not all of the features are present, when symptoms have been modified b
40、y the various factors, or when the ulcer is silent. Peptic ulcer must also be considered with the occurrence of epigastric distress or dyspepsia or with suspicion of gastrointestinal bleeding. lTo diagnose an ulcer, your doctor will order one of the following tests:lDouble-contrast upper GI series:
41、it has been replaced largely by diagnostic endoscopy.lIt is not as sensitive as endoscopy for the diagnosis of small ulcers (0.5 cm).lIt does not allow for obtaining a biopsy to rule out malignancy in the setting of GU or to assess for HP infection.ldirect signs of ulcer: projectionlindirect signs o
42、f ulcer: no valuemotility disorders: irritability in the duodenal bulbspastic incisuratenderness on compression over the site of the ulcer. lPreferred diagnostic test in the evaluation of patients with suspected PUD lHighly sensitive for the diagnosis of PU and provide most reliable diagnosis. lAllo
43、ws for biopsies and cytologic brushings of GU to differentiate a benign ulcer from a malignant lesion lAllows for detection of HP infection with antral biopsies for RUT and/or histopathology. lEstablish the stage of ulcer: active stage, healing stage, scarring stage.lThe majority are small, i.e. les
44、s than 2cm in diameter. Sometimes very large ulcers, up to 10 cm in diameter, may be seen in elderly patients.lBenign ulcers generally have a regular outline and appear to have been punched out of the wall of the duodenum or stomach, i.e. the margins of the ulcer are not heaped up as is often seen i
45、n malignant ulcers. The base of a benign ulcer usually contains a white slough. lThe mucosa surrounding an ulcer is relatively normal - radiating folds may be present due to fibrotic contractures.q溃疡多呈圆形或椭圆形，也有呈线形，边缘光整，底部覆有灰黄色或灰白色渗出物，周围粘膜可有充血、水肿，可见皱襞向溃疡集中。q内镜下分为活动期（A1、A2）、愈合期（H1、H2）和疤痕期（S1、S2）。q可直视发
46、现溃疡，可检测HP，重要的是可活检区别良、恶性溃疡，通过染色、放大等可发现早期胃癌。GU: A1, H1, S1DU: A1, H1, S1Single ulcer in bulb of duodenumAn ulcer of healing stage in gastric antrumDuodenal ulcer: S2 stageAn ulcer in gastric corpus Ulcer of gastric cornerAn ulcer of gastric antrumPyloric channel ulcerNumerous ulcer in bulb and postbul
47、b of duodenumNumerous ulcer of gastric cornerNumerous ulcer of gastric corpusGiant ulcers in bulb and postbulb of duodenumA giant ulcer of gastric cornerComplex and numerous gastric and duodenal ulcerlFunctional dyspepsialZ-E syndromelMalignant GU or infiltrative diseases of the stomach lBiliary col
48、ic, cholecystitis, cholelithiasis 胆石病胆石病lAcute or chronic gastritis, duodenitislGastroesophageal reflux diseaselMesenteric artery ischemialMyocardial ischemialPancreatic cancer, acute or chronic pancreatitislCrohn disease with gastric or duodenal involvement It is a syndrome that nonbeta islet cell
49、tumors of the pancreas cause large amounts of gastrin secretion, marked increase in gastric acid secretion, and ulcer disease of the UGI. Under the following circumstances, Z-E syndrome should be suspected: lFailure of either gastric or duodenal ulcer to heal with optional medical therapy.lDevelopme
50、nt of a complication of PU;lNumerous ulcers in the stomach and/or duodenum or ulcer in unsual locations (e,g, esophagus or jejunum).lPU associated with protracted diarrhealRecurrent ulcer after conventional surgery.lPU associated with large rugal folds in the stomach, duodenal loop, or jejunum.l内镜或X
