Mechanisms underlying excessive esophageal acid exposure in patients with gastroesophageal reflux disease

The cause of reflux esophagitis (RE) is excessive esophageal acid exposure. Acid reflux and acid clearance after acid reflux are important factors related to excessive esophageal acid exposure. The main mechanism responsible for acid reflux is transient lower esophageal sphincter relaxation (TLESR), which is LES relaxation not associated with swallowing, and acid reflux caused by low LES pressure is rare. The frequency of TLESR in the postprandial period does not significantly differ between healthy subjects and gastroesophageal reflux disease (GERD) patients; however, the proportion of acid reflux episodes during TLESR is significantly higher in GERD patients. The layer of acid that appears above the dietary layer immediately below the esophagogastric junction (acid pocket) is attracting increasing attention as a cause of the difference in the proportion of acid reflux episodes during TLESR. The proportion of acid reflux episodes during TLESR is significantly higher when the acid pocket is present in the hernia sac than when it is located below the diaphragm. The acid pocket also shows upward migration and reaches the esophageal side of the esophagogastric junction, and the acid pocket itself has been suggested to cause mucosal damage in the lower esophagus. The amplitude and success rate of primary peristalsis decreases with increases in the severity of RE, leading to excessive esophageal acid exposure. Furthermore, the success rate of secondary peristalsis is lower in GERD patients than in healthy subjects.     

Characteristics of gastroesophageal reflux in symptomatic patients with and without excessive esophageal acid exposure

OBJECTIVE: In some patients with a physiological esophageal acid exposure, an association between reflux episodes and symptoms can be demonstrated. Besides acidity, other factors such as proximal extent may determine whether a reflux episode is perceived or not. We aimed to investigate the reflux profile of gastroesophageal reflux disease (GERD) patients with physiological acid exposure. METHODS: Twenty-four-hour impedance-pH monitoring was performed in 14 GERD patients with excessive acid exposure (pH+), 14 GERD patients with physiological acid exposure (pH-), and 14 controls. All patients had a positive symptom-reflux association during 24-h monitoring (SAP+). RESULTS: The incidence of acid reflux episodes in pH- SAP+ patients (25.5 +/- 4.9) and controls (20.2 +/- 3.9) was comparable, but lower than in pH+ SAP+ patients (69.8 +/- 7.3). However, no differences in number of weakly acidic reflux episodes were observed among pH- SAP+ patients, pH+ SAP+ patients, and controls (27.2 +/- 3.8 vs 26.8 +/- 4.6 and 21.0 +/- 3.7, respectively). The proportion of reflux episodes that reached the proximal esophagus was significantly higher in the pH+ SAP+ (33.5%) and pH- SAP+ (36.0%) patients than in the controls (19.5%). Volume clearance time was longer in pH+ SAP+ (12.5 [12.5-17.0] s) compared with pH- SAP+ patients (12.0 [11.0-16.5] s) and controls (9.5 [10.0-12.5] s) (P < 0.05). Acid clearance time was also longer in pH+ SAP+ patients (55.0 [32.0-64.0] s) compared with the pH- SAP+ (16.5 [11.4-40.0] s) and controls (14 [12.0-19.1] s) (P < 0.01). CONCLUSIONS: In pH- SAP+ patients, a higher proportion of reflux episodes reach the proximal esophagus than in controls. This can in part explain their symptoms.     

胃食管反流病食管酸暴露和食管动力学变化特征

目的探讨无效食管动力(IEM)在胃食管反流病(GERD)中的作用,以及体质量对食管酸暴露及食管动力的影响。方法77例GERD典型症状患者全部行食管高分辨率压力测定(HRM)和24 h食管动态pH监测,分析IEM及正常食管动力患者酸暴露情况。结果 77例典型GERD症状患者中病理性酸暴露者38例(49%),在病理性酸暴露组中IEM 9例(24%),正常酸暴露组中IEM 5例(13%)。IEM组LES压力低于食管动力正常组(15.15±3.60 vs 22.15±6.73,P0.01);IEM组总pH4时间(百分比)较正常食管动力组高[(14.78±3.8)%vs(4.30±2.68)%,P0.01];IEM组患者BMI值较高。结论 IEM在GERD中较常见,其食管动力障碍中绝大多数为IEM,IEM与食管远端酸暴露密切相关。     

胃食管反流病问卷评分对胃食管反流病患者食管酸暴露的预测意义

目的 确定胃食管反流病问卷(GerdQ)症状评分能否反映胃食管反流病(GERD)患者由24 h食管动态pH监测显示的酸暴露情况,进一步验证GerdQ的临床应用价值.方法 纳入2008年11月至2010年3月因烧心等上消化道症状就诊的门诊GERD病例134例,均完成胃镜检查、24 h食管动态pH监测和GerdQ量表.根据...     

Females without reflux symptoms or gastroesophageal reflux disease have less distal esophageal acid exposure than males without reflux symptoms or gastroesophageal reflux disease

Ambulatory 24‐hour esophageal pH monitoring is the gold standard examination to assess esophageal acid exposure. Gender‐related variation is a well‐recognized physiologic phenomenon in health and disease. To date, limited gender‐specific 24‐hour esophageal pH monitoring data are available. The aim of this study was to obtain values of esophageal pH monitoring in males and females without reflux symptoms or gastroesophageal reflux disease (GERD) to determine if gender variation exists in esophageal acid exposure among individuals without these factors. Twenty‐four‐hour dual esophageal pH monitoring was performed in male and female volunteers without reflux symptoms or GERD. Values for total number of reflux episodes, episodes longer than 5 minutes, total reflux time in minutes, % time with pH below 4, and longest reflux episode in the proximal/distal esophagus were obtained and recorded for both groups. The distal channel was placed 5 cm and proximal channel 15 cm above the manometrically determined lower esophageal sphincter. Means were compared using an independent sample t‐test. Sixty‐seven males and 69 females were enrolled. All subjects completed esophageal 24‐hour pH monitoring without difficulty. There was no age or body mass difference between groups. Females had significantly fewer reflux episodes at both esophageal measuring sites and, significantly less total reflux time and % time with pH below 4 in the distal esophagus than males. All other parameters were similar. Significant gender‐related differences exist in esophageal acid exposure, especially in the distal esophagus in individuals without reflux symptoms or GERD. These differences underscore the need for gender‐specific reference values for 24‐hour pH monitoring, allowing for an accurate evaluation of esophageal acid exposure in symptomatic patients.     

Aging and esophageal motility in patients with gastroesophageal reflux disease

BACKGROUND: Alterations of esophageal contractions may worsen the esophageal lesions caused by gastroesophageal reflux. The impairment of the contractions may be localized only in the distal esophagus or in the entire esophageal body, and may be worse with the aging process. AIMS: To evaluate the proximal and distal esophageal contractions in patients with gastroesophageal reflux symptoms with or without esophagitis. PATIENTS AND METHODS: We studied esophageal motility in 104 patients with gastroesophageal reflux symptoms, 42 with normal esophageal endoscopic examination, 47 with mild esophagitis and 15 with severe esophagitis. The esophageal contractions were measured by the manometric method at 2, 7, 12 and 17 cm from the upper esophageal sphincter, after five swallows of a 5 mL bolus of water. RESULTS: The amplitude and area under the curve of contractions were lower in patients with severe esophagitis than in patients without esophagitis or with mild esophagitis in the distal part of the esophageal body (17 cm from the upper esophageal sphincter). In the proximal esophageal body there was no difference in amplitude or area under the curve. In the entire esophageal body there was no difference between the three groups of patients in duration, velocity of peristaltic contractions, or proportion of failed, simultaneous, non-propagated or peristaltic contractions. There was no difference between the patients with less than 50 years or with more than 50 years of age. CONCLUSIONS: Patients with severe esophagitis had lower distal esophageal contraction amplitude than patients without esophagitis or with moderate esophagitis. There was no effect of aging on esophageal contractions.     

胃食管反流病伴或不伴食管损伤与食管动力及酸反流之间的关系

目的 研究胃食管反流病(GERD)患者伴或不伴食管损伤与食管动力和酸反流之间的相关性.方法 对符合GERD诊断标准的25例受试者行胃镜检查,随后进行高分辨率食管测压检查,并检测进食标准试验餐后的动态食管pH值变化.比较伴或不伴食管损伤组患者之间的食管动力和餐后食管酸反流时间的差异.同时按DeMeester评分将受试者分为非酸反流组和酸反流组,比较两组食管动力学指标的变化.统计学处理采用t检验和秩和检验.结果 伴或不伴食管损伤组之间下食管括约肌(LES)压力基础值、LES压力残余平均值、食管蠕动传播速度、食管pH＜4的时间和DeMeester评分均差异无统计学意义(P均＞0.05),但是伴食管损伤组的食管收缩幅度明显弱于不伴食管损伤组(31.9 mm Hg比64.2 mm Hg,1 mm Hg=0.133 kPa;Z=-2.37,P=0.02).酸反流组和非酸反流组之间LES压力基础值、LES压力残余平均值、食管蠕动传播速度差异均无统计学意义(P均＞0.05),但酸反流组的食管收缩幅度明显弱于非酸反流组(36.4 mm Hg比71.8mm Hg;Z=2.25,P=0.02).结论 GERD患者LES压力及食管酸反流与食管损伤之间无显著关系,食管蠕动性收缩功能可能与食管损伤及酸反流有关.     

轻度反流性食管炎与非糜烂性反流病远端食管酸暴露和食管动力学变化

目的:探讨轻度反流性食管炎(RE)与非糜烂性反流病(NERD)食管远端酸暴露及食管动力变化特点.方法:符合洛杉矶诊断标准的RE30例(LA-A16例,LA-B14例),NERD16例,健康对照组10例被纳入本研究,所有患者及对照组均接受24h食管pH监测及压力测定,比较食管pH监测及测压结果.结果:LA-A组、LA-B组、NERD组DeMeester评分明显高于对照组,差异显著(P<0.05).LA-A组与NERD组比较DeMeester评分无明显差异,但NERD组的立位反流时间百分比与长反流周期数多于LA-A组,差异显著;LA-B组DeMeester评分比LA-A组和NERD组明显增高,LA-B组与LA-A组比较食管pH监测各项指标均存在明显差异.LA-A组、NERD组及对照组比较下食管括约肌静息压(LESP)、食管体部蠕动波幅度(PA)无显著差异,LA-A组和NERD组食管下段PA有增高趋势;LA-B组与LA-A组、NERD组及对照组比较LESP明显降低(P<0.05),LA-B组食管下段PA明显低于LA-A组(P<0.05).RE组无效食管运动(IEM)明显高于对照组,差异显著.结论:轻度RE(LA-B)与NERD远端食管酸暴露存在差异.DeMeester评分、LES功能不全及食管蠕动功能障碍与RE的严重程度呈正相关.LES功能不全及食管蠕动功能障碍可能不是轻度RE(LA-A)及NERD的主要致病因素.IEM与RE关系密切,且与RE有关的食管动力异常主要为IEM.     

胃食管反流病中医分型与酸反流的关系

目的研究胃食管反流病(gastroesophageal reflux disease,GERD)的中医的辨证分型与酸反流各项指标的关系,为本病辨证分型寻求特征性的客观指标.方法通过对97例经24 h食管pH值动态监测和内镜检查确诊为GERD的患者的临床观察,以临床四诊资料为基础,在中医理论指导下,对其进行病位、病性、病因、病机的辨证分析,从而筛选出本病的主要证型.在此基础上,选用24 h食管pH值动态监测的多项酸反流指标,运用多种统计学分析方法,研究各主要证型与食管酸反流多项指标之间的关系.结果 GERD 97例的辨证分型筛选出的主要证型有肝胃郁热、肝胃不和、脾胃虚弱、胃热气逆、痰气郁阻5型.总反流次数在肝胃郁热型中显著高于肝胃不和、脾胃虚弱、痰气郁阻型,在胃热气逆型中显著高于脾胃虚弱、痰气郁阻型(P＜0.05);总pH＜4时间百分率和反流总分在肝胃郁热、肝胃不和、胃热气逆型中显著高于脾胃虚弱型(P＜0.05).酸反流的症状指数≥50%病例数的百分率在肝胃不和、肝胃郁热、胃热气逆型中极显著高于其余各证型(P＜0.01).酸反流体位分型为混合型的病例数的百分率在脾胃不和、痰气郁阻型中显著高于其余各证型(P＜0.05).结论 GERD的中医辨证分型与某些食管酸暴露参数之间存在明显关系.     

十二指肠胃食管反流在胃食管反流病中的作用

目的　研究十二指肠胃食管反流 (DGER)在胃食管反流病发病机制中的作用及其对非糜烂性反流病 (NERD)的诊断价值。方法　 95例患者根据内镜检查的结果分为反流性食管炎和NERD组 ,对其均进行 2 4h食管 pH和胆汁联合监测。 结果　反流性食管炎患者DGER的各项指标 :吸光度值 >0 14时间百分比 (% )、总反流次数和反流 >5min的次数分别为 19 0 5± 2 3 4 4、30 5 6±34 0 4和 5 90± 6 37,均显著高于NERD组相应的 7 2 6± 11 0 8、15 6 8± 2 0 92和 2 5 9± 3 5 7(P <0 0 5 ) ,而酸反流差异无显著性 ,随着反流性食管炎的程度加重DGER发生率增高 ;18 2 %的NERD患者存在单纯DGER ,联合胆汁监测可使NERD诊断阳性率由 6 5 9%升高到 84 1%。结论　DGER可以单独发生 ,在引起反流性食管黏膜损伤或症状方面都有作用 ,2 4h食管 pH和胆汁联合监测有助于NERD的诊断。     

Dilated intercellular spaces of esophageal epithelium in nonerosive reflux disease patients with physiological esophageal acid exposure

OBJECTIVES: It has been demonstrated that dilation of intercellular spaces of esophageal epithelium is a marker of tissue injury in GERD patients with a pathological esophageal acid exposure time. To evaluate the relationship among ultrastructural changes, acid esophageal exposure, and GERD symptoms, intercellular space diameters have been assessed in nonerosive reflux disease (NERD) patients with/without abnormal acid exposure time. METHODS: Following a pharmacological wash-out, 20 NERD patients underwent upper endoscopy, esophageal manometry, and 24-h pH monitoring. Biopsies were taken at 5 cm above the lower esophageal sphincter and intercellular space diameters were measured on transmission electron microscopy photomicrographs. Seven asymptomatic controls underwent the same protocol. RESULTS: Acid exposure time was in the normal range in all controls and in 11 patients (NERD pH-negative); it was abnormal in 9 patients (NERD pH-positive). Mean intercellular space diameter in NERD pH-negative and in NERD pH-positive patients was three times greater than in controls (1.45 and 1.49 microm vs 0.45, p < 0.001). Mean values of maximum intercellular spaces in all NERD patients were greater, two-fold or more, than those in controls (p < 0.001). No difference in mean and maximal space diameters was observed between NERD pH-positive and pH-negative patients. CONCLUSIONS: Dilation of intercellular spaces is a feature of NERD patients, irrespective of esophageal acid exposure, and can be considered an objective, structural marker of GERD symptoms. Impaired esophageal mucosal resistance, even to small amounts of acid refluxate, plays a key role in the pathophysiology of NERD.     

Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure

Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy‐negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty‐three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty‐five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity.     

六味安消对非糜烂性反流病患者食道动力及酸反流的影响

[目的]观察六味安消对非糜烂性反流病（NERD）患者食道动力及胃食管反流的影响,并与莫沙必利比较疗效.[方法]选取具有典型胃食管反流症状的NERD患者52例,行胃食管反流症状评估、食管测压及24 h pH监测,随机分成试验组26例和对照组26例.给予药物治疗（试验组六味安消,对照组莫沙必利）4周后,对比治疗前后临床症状、食管动力学及胃食管反流的改变情况.[结果]试验组与对照组症状总积分、食管蠕动功能、pH＜4反流次数、反流＞5 min次数、总计pH＜4的百分比、DeMeester评分自身治疗前后相比较,差异均有显著统计学意义（P＜0.05）,而2组组间比较差异均无统计学意义.[结论]六味安消能有效缓解NERD患者的胃食管反流症状,改善食管蠕动功能及减少酸反流.     

胃食管反流病患者夜间反流与睡眠障碍情况调查

目的 研究胃食管反流病(GERD)患者夜间反流症状、睡眠障碍的发生率及相互关系.方法 全国51个城市的125家医院对7520例门诊GERD患者进行问卷调查.获得有效问卷7515份,男、女比例为1.36∶1.调查项目包括:GERD症状、夜间反流症状发生率、睡眠障碍的表现及夜间反流与睡眠障碍的关系.结果 GERD主要症状为烧心(88.3%)、反流(72.2%)、胸痛(37.6%)、上腹痛(35.5%)、咽部不适(30.4%)、咳嗽(12.1%)及哮喘(3.0%).7515例患者中,有夜间症状者4216例(56.1%),经内镜证实的糜烂性食管炎(EE)及非糜烂性胃食管反流病(NERD)患者夜间反流症状发生率分别为56.1%及53.1%,两者间差异无统计学意义(P＞0.05).有夜间反流症状者80.1%存在睡眠障碍,明显高于无夜间反流症状者的25.8%(P＜0.01).在睡眠障碍中,以睡眠质量下降和日间残留效应为多(分别为78.2%和70.1%),有夜间反流症状者,睡眠障碍病程发生在反流症状之后的占58.7%,明显高于发生在反流症状之前的21.5%(P＜0.01).有夜间反流的EE及NERD患者的睡眠障碍发生率分别为80.0%及77.1%,两者间差异无统计学意义(P＞0.05).在治疗GERD伴睡眠障碍方案中以质子泵抑制剂治疗为主(53.8%),其次为安眠药(24.5%),联合用药(9.5%).结论 GERD患者常有夜间反流症状及睡眠障碍,夜间反流可能是患者睡眠障碍的原因,治疗中应合并使用质子泵抑制剂.     

无效食管运动在胃食管反流病中发病作用的观察

目的　探讨食管无效收缩 (IEM)在胃食管反流病 (GERD)的发病作用。方法　对GERD病人行食管测压和 2 4h食管pH监测 ,分析IEM在GERD的发生率以及比较IEM与食管酸暴露、酸清除和食管炎的关系。结果　 86例GERD病人中 5 9例 (6 8 6 % )存在非特异性食管动力障碍 (NEMD) ;其中 5 5例 (占 93 2 % )符合IEM诊断标准 ;GERD病的IEM发生率为 6 3 95 %。IEM的GERD患者总的pH <4时间 (% ) (5 91)及立位 (4 4 3)和卧位 (6 92 )pH <4时间 (% )显著大于食管正常蠕动的GERD患者 (分别为 3 16 ,1.6 1,和 4 31) ,尤以卧位明显 (P <0 0 1)。IEM患者平均卧位食管酸清除时间 (EAC)为每次 12 6 3min ,显著长于正常食管动力GERD患者的每次 3 15min(P<0 0 1) ,而立位EAC则与正常食管动力组无差异。 2 7例正常食管动力GERD有 10例 (37% )有糜烂性食管炎 ;5 5例IEM患者有 19例 (35 % )有食管炎 ,二组间食管炎发生比例差异无显著性 (P >0 0 5 )。结论　GERD病的食管动力障碍大多数系IEM。IEM比正常食管动力患者更易发生反流和存在食管酸清除障碍。IEM是GERD病的主要异常表现。