Clinical presentations

Esophageal presentations attributed to GERD vary according to the age of the patient, and include regurgitation, irritability, arching, and feeding aversion in infants, and vomiting, chest pain, heartburn, and abdominal pain in older children. Circumstantial evidence strongly suggests a relationship between reflux and a variety of extraesophageal presentations. These extraesophageal manifestations involve the airways or dental erosions. The former are best appreciated in light of the intricate...

The development of neoplasia

Dysplasia is the first step in the neoplastic process. It represents a change in the cytologic characteristics of cells and the glandular architecture detected histologi-cally. The progression of neoplasia can result in cancer - in BE that means EAC. Although the incidence of EAC in BE is controversial, both cohort studies 8 and a funnel analysis of the literature estimate the incidence at 0.5 per year 9 . A more realistic estimate may be the lifetime risk - younger patients do not have a...

Symptoms

The classic symptoms of GERD are heartburn and acid regurgitation, and the presence of these symptoms can be considered diagnostic of the condition, and are sufficient to institute empiric therapy. Elderly patients in a primary care setting commonly Table 1. Prevalence of heartburn in the elderly Table 1. Prevalence of heartburn in the elderly report heartburn, with a prevalence of approximately 15 8 . However, elderly patients often report less severe reflux symptoms, especially in relation to...

Atypical manifestations of GERD

Many extraesophageal (or supraesophageal) manifestations of GERD are now acknowledged as parts of the disease spectrum 24 we disagree with considering these manifestations as only possible complications of the NERD category, as proposed by Fass and Ofman. If, in fact, it holds true that the majority of such patients do not show esophageal mucosal damage at endoscopy, a definite proportion, between 20 and 30 of such patients do indeed have erosive or ulcerative esophagitis 25 . We too dispute...

Clinical efficacy Lifestyle modifications

Several modifications of habits are recommended for patients with GERD. These include rising of the head of the bed, early evening meals with sufficient time to elapse before going to bed, weight reduction, stopping smoking and avoidance of alcoholic beverages etc (for overview, see 22 ). None of these measures have been studied with sufficient quality so far. Therefore, its merits - if there are any - cannot be evaluated based employing the methods of evidence-based medicine. Certainly, some...

Medical Therapy Of Gastrooesophageal Reflux Disease

Innere Klinik, HELIOS Klinikum Berlin-Buch, Berlin, Germany Treatment of gastro-oesophageal reflux disease (GERD) has to take into account that GERD shows a considerable variation in the way of manifestations the spectrum ranges from intermittent heartburn of minor severity to severe daily symptoms additionally, dysphagia and bleeding may be due to complications such as strictures and oesophageal ulcers. Furthermore, gastro-oesophageal reflux has also been linked to a number of symptoms of...

Esophageal

Regurgitation and vomiting are the most easily recognizable symptoms of pediatric reflux. Episodes are usually effortless, non-bilious and post-prandial. It is usually the quantity and type of emesis that differentiates physiologic reflux in happy spitters from symptomatic reflux in infantile GERD. Some children have persistent or intermittent symptoms beyond the first year of life. Projectile non-bilious emesis in the first few weeks of life may mimic hypertrophic pyloric stenosis but simply...

Drug therapy

Several controlled trials have been performed comparing the effect of different acid inhibitory drugs in the treatment of reflux oesophagitis (erosive reflux disease ERD). Data on the effect of acid suppression in non-erosive reflux disease (NERD) are less frequent in particular, studies comparing the effect of PPI and H2-blockers are scare. In patients with ERD (Table 1), PPI have been shown to be much more effective than H2-receptor antagonists in terms of healing of erosions, resolution of...

Screening for and surveillance of Barretts esophagus

Screening is looking for the premalignant disease BE, and surveillance is evaluating the premalignant disease for the early detection of HGD or EAC. The rationale for screening is to detect BE in order to recognize early prevalent HGD and EAC and to appropriately control reflux symptoms. Less than 5 of patients surgically treated for EAC have had BE previously identified 12 . The only opportunity for improved outcome in the highly fatal disease EAC is early detection and effective intervention....

Treatment

The medical and surgical treatment of GERD in the elderly population generally follows the same principles as for any adult patient with reflux 10 . The basic goals of treatment are relief of symptoms, early detection of lesions, healing of esophagitis, prevention of relapses, and prevention of complications 28 . Evaluation and management of the elderly patient does require attention to more subtle, atypical, or non-specific symptoms, recognition of the importance on maintaining function, and...

Conclusion

Theories of the mechanism of gastroesophageal junction competence have seesawed between strictly anatomic explanations, focusing on type-I hiatus hernia, and physiologic explanations focusing on the vigor of LES contraction while ignoring the significance of anatomic factors. As detailed above, current thinking recognizes contributions from both sphincteric components. Furthermore, there is an increasing understanding of mechanical elements of the antireflux barrier, inclusive of, but nor...

Genetic factors

Familial aggregation for GERD, in general, was not demonstrated, but investigators were able to document a significant rate of familial occurrence for both Barrett's esophagus and esophageal adenocarcinoma 64 , 65 . Recently, a large twin study has shown an increased concordance for GERD in monozygotic pairs, compared with dizygotic pairs, suggesting that genetic factors accounted for 31 of the liability to GERD in the U.S. population 11 , 66 . Furthermore, a genetic linkage study in pediatric...

Natural history

Infantile GERD is generally regarded to have a favorable natural history, with persistent symptoms in about 5 of infants by one year of age, following a peak at 4 months, and resolving in the large majority between 12 and 24 months of age 7 , 8 . Epidemiological studies of the natural history of GERD and its complications in older children are scarce 9 . Un-selected infants with frequent regurgitation may develop feeding problems in the subsequent year of follow-up 10 . Children with chronic...

Refluxate

The pathogenicity of the refluxate is determined by the noxiousness of its constituents namely, acid, pepsin, trypsin, and bile salts. Acid in combination with pepsin has been found to be the most injurious to the esopha-geal mucosa. Most patients with reflux have normal gastric pH, and it has been suggested that volume rather than acidity of the refluxate may be more important in the pathogenesis of reflux. Infants, including premature infants of 24 weeks gestation, maintain that basal gastric...

Diagnosis

There are several factors complicating the diagnosis of GERD in the elderly, and the diagnostic approach in this group should be different than in a younger population. When a healthy young patient presents, with the classic symptoms of heartburn or acid regurgitation, no further testing is needed to diagnose GERD. In this case, the recommendations are to treat first, and reserve diagnostic testing for those with alarming or atypical symptoms, symptoms resistant to medical therapy, those with a...

Utility of endoscopy in addition to confirmation of diagnosis

In patients with atypical symptoms or symptoms over and above those of typical reflux, endoscopy may also have utility in ruling out alternative diseases, such as peptic ulcer disease, eosinophilic esophagitis and complications like adenocarcinoma. Eosinophilic esophagitis, also known as primary eosinophilic esophagitis or idiopathic eosinophilic esophagitis, occurs in adults and in children and represents a subset of eosinophilic gastroenteritis with an isolated severe esophageal eosinophilia....

The diaphragmatic sphincter and hiatus hernia

Endoscopic and radiographic studies suggest that 50-94 of patients with gastroesophageal reflux disease (GERD) have a type-I hiatal hernia while the corresponding prevalence in control subjects ranges from 13-59 37 - 40 . Most patients with severe esophagitis have a hiatal hernia 41 , 42 and 96 of patients with Barretts esophagus have a > 2 cm hiatus hernia 43 . However, the importance of a type-I hiatal hernia is obscured by the misconcep tion that this is an all or none phenomenon. It is...

Conservative therapy

Most guidelines recommend instituting lifestyle changes (Table 4) at the same time as empiric therapy. Lifestyle modifications are considered useful in reducing symptoms, but there are few data to support an impact on healing the esophagus, or any proven long-term benefits 13 . Physiologic studies show that elevation of the head of the bed, decreased fat intake, cessation of smoking, and avoiding recumbency for 3 hours post-prandially decreases distal esophageal acid exposure - Elevation of...

Endoscopically normal mucosa

The absence of changes in the distal esophagus on conventional endoscopy does not rule out the diagnosis of GERD. It is estimated that upto 70 of patients with typical symptoms of GERD have normal esophageal mucosa on upper endoscopy (NERD) 4 , 6 , 7 . At least, two different approaches have been attempted in these patients biopsies of the normal appearing squamous mucosa and evaluation of the distal esophagus with newer techniques such as high resolution and magnification endoscopy....

GERD complications

GERD comprises a spectrum of disease, ranging from non-erosive esophagitis, to complications involving increasingly severe esophageal damage. Complications of reflux disease include erosive esophagitis, esophageal ulceration, peptic stricture, BE, and ade-nocarcinoma of the esophagus. Several studies have shown that complications of GERD tend to occur together. Any GERD complication is 10 times more likely to occur with another GERD complication than without, and this is most often true for...

Mechanisms for heartburn

The mechanisms by which patients with GERD develop symptoms remain incompletely understood. It is postulated that sensitization of esophageal chemo-receptors either directly by exposure to acid reflux or indirectly through release of inflammatory mediators CA Carbonic anhydrase ICS - Intercellular Space CA Carbonic anhydrase ICS - Intercellular Space Fig. 3. Epithelial defenses against acid injury that include,cell membrane, intercellular junctional complexes, intracellular buffering and HCO3...

The clinical context of Barretts esophagus

BE is most commonly recognized as part of the endoscopic evaluation of patients with chronic heartburn and or regurgitation - the most common symptoms of GERD. On a population basis, 5 of adults with chronic GERD have BE 5 . Recently there has been increasing assessment of asymptomatic individuals undergoing colon cancer screening for BE. In a small predominantly male (90 ) Veteran study, 25 of subjects lacking reflux symptoms had BE - 7 long segment (> 3 cm) 6 . In a larger study of a more...

Incidence and prevalence of GERD symptoms

The first and probably more quoted paper concerning the incidence of GERD symptoms is the study by Nebel et al, published in 1976 40 the study was conducted by means of a questionnaire administered to 446 hospitalized and 558 non-hospitalized subjects, as well as in 385 control subjects. In the latter group, daily heartburn occurred in 7 , weekly in 14 and monthly in 15 , giving a total of 36 of subjects having heartburn at least monthly 40 . Data coming from a large national poll 41 about...

Mortality

GERD would appear to be associated with a very low adult mortality rate. According to Brunnen et al 33 , the annual mortality rate from severe esophagitis was 0.1 per 100,000 from 1951 to 1957. When the operative mortality was considered, this figure rose to 0.16 per 100,000. Kieser 51 found that there have been 47 deaths in Switzerland (population in 1963, 5.8 million) from 1963 to 1964 in which hiatal hernia had been a basic, a contributing or an immediate cause of death, leading to a...

GABA antagonists

The neurotransmitter y-butyric acid (GABA) has been shown to be involved in the initiation of transient sphincter relaxations of the lower oesophageal sphincter (LES) which are thought to play the major role in the pathophysiology of reflux disease. Attempts have been made to suppress these relaxations not associated with swollowing, e.g. by the prototype of GABAb receptor agonist, baclofen. In fact, GABAergic stimulation increases the pressure in the lower oesophageal sphincter 7 . So far,...

Clinical Spectrum Natural History And Epidemiology Of Gerd

Chair and Department of Gastroenterology, L. SaccoUniversity Hospital, Milan, Italy GERD is a spectrum disease, i.e., a disease composed by many patient subgroups, ranging from symptomatic disease without mucosal lesions (or NERD) to the complications of erosive esophagitis, such as esophageal stricture, ulceration or Barrett's esophagus. Almost all the transitions are possible amongst groups, even if the progression from one stage to the other has been described mainly based upon retrospective...

Definitions 1 NERD

Patients with NERD do not, by definition, have esophagitis and appear to be at low risk to develop esophagitis NERD is best defined, therefore, on the basis of symptoms and or their impact on an individual's health-related quality of life (QOL) 4 . Indeed, it is apparent that NERD patients can, and do, suffer from symptoms as severe as those with ERD, and the impact on quality of life can be at least as disabling in NERD as in other manifestations of GERD 5 , 6 . It is appropriate, therefore,...

Epidemiology

Gastroesophageal reflux disease is defined as an increased frequency or duration of exposure of the distal esophagus to gastric contents. GERD is a chronic disease, that rarely resolves spontaneously, and it is associated with frequent relapses. Several studies have investigated the prevalence of GERD, though few have specifically targeted the elderly. In the 1970's, Locke et al studied the prevalence of reflux symptoms in the general population using a group of hospital workers in Olmsted...

Effect of Helicobacter pylori eradication on GORD symptoms and severity

The actual data range from a more beneficial to an harmful or simply no effect of Helicobacter pylori eradication on GORD. The first report of Labenz et al on an increase of the incidence of oesophagitis in ulcer patients after Helicobacter pylori eradication has been confirmed by further studies in patients with corpus predominant gastritis and associated hypochlorhydria. The effect was attributed to the recovery of acid secretion after Helicobacter pylori eradication 15 , 16 . Further studies...

Proton pump inhibitors

Today, proton pump inhibitors (PPI) are the drug of choice for the vast majority of patients with GERD. This class of drugs consists of substituted benzimid-azoles which are prodrugs activated at low pH in the parietal cell. After entering the acid space of the parietal cell, PPI are transformed to a sulfenamide, a tetracyclic compound which covalently binds to the H+ K+-ATPase (proton pump). The ability of the individual parietal cell to regain its function of acid production is restored by...

Prevalence

The percentage of patients with reflux symptoms found to have esophagitis at endoscopy varies notably in the published series, from 38 to 75 35 , with an average of 50 or less 36 . Indeed, several recent community-based European studies found even a lower prevalence, of about 30 37 , 38 . In large endo-scopic series, reflecting the percentage of patients in general gastroenterological practice, the prevalence of esophagitis is nowadays higher than that of duodenal and gastric ulcer, and ranks...

Antacids

Antacids act by neutralising acid thus leading to prompt disappearance of symptoms. Therefore, antacids regularly serve as rescue medication in studies on the effect of acid inhibitory compounds and are also preferred by patients with sporadic heartburn. However, antacid consumption several times a day (which indicates the presence of reflux oesophagitis) should not be encouraged intake of high doses of antacids inherits a lot of problems (diarrhoea due to magnesium, aluminium-induced...

Genetics

GERD and its complications are recognized as clustering within families, suggesting a genetic background for GERD phenotypes. A gene mapped for severe pediatric GERD with prominent respiratory symptoms in five kindreds was localized to chromosome 13q14 15 . Later, a genetic linkage for infantile esophagitis was identified at a separate locus 16 . A candidate gene approach to screen for mutations that might be causally associated with reflux suggests that a GERD1 gene on chromosome 13q14 might...

Incidence and prevalence of esophagitis

Studies concerning the incidence rate of reflux esophagitis (RE) and or GERD are very rare historically, the first study on the incidence of (severe) RE was published in 1969 by Brunnen 33 , who gave a figure of 4.5 per 100,000 for ulcerative esophagitis or RE complicated by stricture. The study was conducted among residents older than 12 years from the northwestern region of Scotland, and it comprised a total of 200 patients. The occurrence of esophagitis was confirmed by barium studies in...

Esophageal dysmotility

Gastroesophageal reflux is the result of transient LES relaxation, stress reflux or an abnormally low LES pressure (free reflux or the common cavity phenomenon) (see Fig. 2). The goal of normal esophageal peristalsis and gravity is to eliminate nearly all of the refluxate from the esophagus, allowing the residual acid to be neutralized effectively by bicarbonate-rich saliva 15 . Impairment of acid clearance can be secondary to either peristaltic dysfunction and or re-reflux (the to-and-fro...

Erosive Gerd Erd

The above quoted paper by Fass states that patients with erosive esophagitis tend to remain within this group during their lifetime and that Barrett's mucosa does not progress or regress over time, and thus patients continue to harbor this type of lesion as long as they live. In fact this is not true, as transition to Barretts esophagus and to adenocarcinoma has been reported, the latter even in the absence of BE as an intermediate lesion. We have already mentioned the 11 of new developed BE...

Mechanical properties of the relaxed EGJ

In contemplating the occurrence of reflux in the setting of a relaxed or hypotensive sphincter it is also necessary to consider other mechanical attributes of the system that may account for a relaxed sphincter remaining closed in one case and physically open in another one such attribute is compliance, or distensibility of the sphincter. Acquired anatomic changes inclusive of, but not restricted to, hiatus hernia may alter the compliance at the relaxed EGJ thereby decreasing the resistance to...

Morbidity

The morbidity from GERD arises from both esopha-geal and extra-esophageal complications. GERD ac counts for only approximately 6 of massive upper gastrointestinal hemorrhage 48 . More recent data show that this figure is probably increasing, possibly due to the overall increase of GERD prevalence. For example, Newton et al 49 found that in a inpatient population undergoing upper GI endoscopy at a district general hospital, 58 were referred to gastroscopy for investigation of acute upper...

Management

Of interest, several studies as well as recent reviews and meta-analyses, while confirming a significant response, in terms of symptom relief, to proton pump inhibitors in NERD, have demonstrated, with some consistency, that these agents are somewhat less effective in NERD 3 , 9 , 59 , 62 - 68 than in ERD 69 . Several factors might explain this somewhat unexpected finding and include the relatively greater importance of abnormal acid exposure in ERD and the significant overlap with functional...

Maintenance therapy

A high percentage of patients with GERD require long-term, possibly lifelong therapy for symptom control. Maintenance therapy keeps the symptoms under control, and prevents development of complications. After complete healing of esophagitis with omepra-zole, recurrences occur in up to 82 of patients within 3-6 months if no maintenance therapy is given. Early recurrence has been associated with a hypotensive LES, long-standing symptoms, need for long-term treatment for initial symptom relief and...

The refluxate

There is evidence to suggest that both acid and duodenal contents, mainly pepsin (an acid activated proteolytic enzyme) and bile salts (conjugated and de-conjugated), are noxious to the esophageal mucosa 25 , 26 . However, typically gastric content is acidic, making acid and pepsin the main noxious agents in the refluxate. Original studies reported that deconju-gated bile salts and pancreatic enzymes are rendered ineffective at acidic pH (inactivated) 27 , 28 . Furthermore, bile salts do not...

Pathophysiology

While gender and age are by no means absolute discriminators for any group of GERD, it is noteworthy that, in contrast to GERD, in general, females do predominate in NERD, a group who, on the whole, tend to be younger, by a factor of about a decade, than their erosive GERD counterparts. Existing data on the pathophysiology of NERD suggest that while, as in ERD, acid and pepsin play a central role in the induction of symptoms, abnormal esophageal acid exposure cannot be the sole mechanism. Thus,...

The role of cagApositivestrains in patients with Barretts oesophagus

An important marker of the virulence of Helicobacter pylori strains is cagA encoding the cytotoxin-associated gene protein (cagA) 4 . Almost all Helicobacter pylori isolates from patients with peptic ulcers, atrophic gastritis and gastric cancer are cagA+ 56 . As there is an inverse relation between carcinoma in the cardia and lower oesophagus and colonization with cagA+ strains 57 it has been proposed that Helicobacter pylori colonization with especially cagA+ strains may protect against the...

References

1 Sampliner RE (2002) Practice Parameters Committee ACG. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus. Am J Gastroenterol 97 1888-1895 2 Blot W, Devesa SS, Kneller RW, Fraumeni JF (1991) Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 265(10) 1287-1289 3 Brown LM, Devesa SS (2002) Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N Am 11 235-256 4 Boyce HW (2000) Endoscopic...

Therapy of nonerosive reflux disease

Since PPI are also the most effective therapy in NERD, it is advisable to start treatment with these compounds. However, results from treatment in patients with NERD are much more complex. This has to be ascribed to the heterogenous population solely based upon a careful history of symptoms it is not always possible to exclude patients with predominant non-acid reflux or aerophagia who often also report to suffer from heartburn, but who will eventually not respond to acid inhibitory drug. Thus,...

Treatment of acute reflux symptoms

For practical reasons it seems important to review the optimal strategy in a given patients depending upon presence or absence of information about the results of endoscopy. Thus, empirical therapy and treatment of ERD and NERD are discussed separately. Another questions also has also to be considered particularly in respect to empirical treatment should we increase the efficacy of medical therapy in relation to its symptomatic effect (step-up'') or should we initially employ the most effective...

Treatment of therapeutic failure

Several reasons may be responsible for the failure of drugs as antireflux therapy (Table 2). Probably the by far most important factor is inadequate inhibition of acid secretion. This may be due to administration of H2-recptor antagonists which do not produce sufficient acid suppression to control reflux symptoms and achieve healing of peptic lesion. Furthermore, also standard doses of PPI are not effective either in about 10-20 of subjects. Thus as a logical consequence PPI should be...

Therapy of reflux oesophagitis

Treatment of choice is the administration of PPI. Within 6-8 weeks, oesophagitis has healed in up to 90 , and more than half of the patients are free of heartburn after the first week. Though disappearance of symptoms is a valuable predictor of effective healing 8 , discrepant results can be detected in up to 20 however, in such cases residual lesions are predominantly minor in asymptomatic patients or heartburn of little intensity in healed cases. Healing rates are influenced by the initial...

The role of cagApositivestrains in patients with oesophageal adenocarcinoma

Different studies hint on a protective role of Helicobacter pylori infection - especially cagA+-strains - against the development of oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma increased over the last years 59 reaching 4-12 per 100.000. This is in contrast to the decreasing incidence of non-cardia gastric cancer (Fig. 3), 63 . Quddus et al did not find any Helicobacter pylori infected in 19 patients with Barrett's adenocarcinoma 60 . In a larger study population...

Longterm strategy

Once a patient has been shown to improve with acid suppression therapy, the question of long-term management becomes evident. Since GERD is in most instances a chronic (relapsing) disease, a concept for the further treatment is needed in the vast majority. The speed of recurrence of symptoms after cessation of treatment represents a reliable predictor for the necessity of ongoing therapy those who will become symptomatic within a few days after stopping treatment will probably require (almost)...

Conclusions

Endoscopy is relatively insensitive for making the diagnosis of gastro esophageal reflux disease. However, the presence of erosive esophagitis and or BE is highly suggestive of GERD. The presence of normal mucosa at endoscopy does not rule out the diagnosis of GERD. At present, the role of biopsies in these situations is unsettled and more data are needed. Newer endoscopic techniques such as chromoendoscopy, magnification and high resolution may demonstrate minimal changes in the distal...

Empirical therapy

In patients with symptoms suggestive of GERD, in many instances it will be impossible to gain access to immediate endoscopy or prompt endoscopy appears not necessary at an early stage but rather an exaggerated diagnostic procedure. This seems, according to recent data of the CADET-PE study 27 , appropriate since reflux disease is by far the dominating endoscopic diagnosis whereas other benign diagnoses (e.g., peptic gastro-duodenal ulcers) were much less frequent and malignancies were rare and...

The disease

Barrett's esophagus (BE) is a change in the lining of the distal esophagus from the normal squamous epithelium to a columnar appearing mucosa with intestinal metaplasia demonstrated by biopsy 1 . Endoscopy with biopsy of the abnormal appearing distal esophagus is necessary to meet the current working definition of BE. Intestinal metaplasia (IM) is an epithelium with goblet cells like the small intestine but with a different architecture reflecting the result of an underlying chronic...

Assessment

Can one predict NERD on the basis of clinical evaluation While the NERD patient is, on average, younger and more likely to be female that the individual with complicated GERD, these demographic features are not sufficiently discriminating to be of diagnostic value. In terms of typical GERD symptoms, neither severity nor duration can discriminate between NERD and GERD, or predict complications or manometric or pH study results. Some atypical or extraesophageal symptoms, in contrast, tend to be...

Antacids Alginic acid

Antacids work locally to increase the pH of the reflux-ate, neutralizing the acid. The increase in pH-causes pepsin to become inactive, and may also prevent the Table 6. GERD therapy in the elderly - Relief of mild moderate symptoms (20 ) - Must be upright for effect (alginic acid) - Useful for dyspeptic symptoms - nausea, gas, bloating - Fatal arrhythmias (Cisapride) - Poor side effect profile - crosses blood-brain barrier (CNS toxicity) - Anti-cholinergic effects (Bethenechol) - Provides...

Surgery

As life expectancy increases, the number of elderly patients presenting with surgically correctable diseases will increase. However, elderly patients are often medically managed despite refractory symptoms due to fear of surgical morbidity and mortality 27 . There has been reluctance to refer elderly patients for lapa-roscopic surgery until complications develop, sometimes despite the presence of continued symptoms on appropriate medical therapy 82 . However, many elderly patients are not...

NERD and dyspepsia

As overlap between these functional syndromes comes to be accepted as a clinical reality, it has posed a dilemma for those who seek to develop precise clinical definitions for the individual functional disorders. For example, where does NERD end and functional dyspepsia begin 51 This is far more than an issue of semantics the inclusion of patients with predominant heartburn in a dyspepsia study population which examines the response to an acid-suppressing agent will significantly bias the study...

Esophageal mucosal defense mechanisms

The esophageal defensive system includes several basic mechanisms. The anti-reflux barrier (LES and the crural diaphragm) and the clearance mechanism that limit the frequency and volume of the refluxate as well as the duration 36 . The third defense mechanism is the esophageal mucosal resistance, which prevents injury by acid, pepsin and other components of the refluxate. Tissue resistance is constituted of structures grouped in three areas pre-epithelial, epithelial and post-epithelial 36 ....

Extraesophageal

Extraesophageal Reflux Symptoms

Apnea is a frequently cited extraesophageal manifestation of reflux in infants, but the causal relationship is controversial, despite being examined by multiple investigators. Most episodes of apnea of prematurity occur in the post-prandial period, and likely follow bouts of regurgitation, and yet studies using impedance and monitoring cardiorespiratory events have been contradictory 52 , 53 . In 21 infants with a history of intermittent reflux and apnea, 81 of apneic events did not follow...

Complicated GERD

The important esophageal complications of chronic reflux are strictures, Barrett's esophagus, and adenocarcinoma. Aggressive medical management, preferably with proton pump inhibitors, and close follow-up, using tests to assess symptoms and severity of reflux, are warranted in complicated GERD. Surgical management is contemplated in patients who remain unresponsive to medical therapy. Exposure of the esophagus to acid and perhaps to pepsin is crucial to the pathogenesis of reflux strictures...

Lower esophageal sphincter intrinsic sphincter hypotension

Gastroesophageal reflux disease can occur in the context of diminished LES pressure either by strain-induced or free reflux. Strain-induced reflux occurs when a hypotensive LES is overcome and blown open in association with an abrupt increase of intraabdominal pressure 34 . Manometric data suggest that this rarely occurs when the LES pressure is greater than 10 mmHg 34 , 35 . It is also a rare occurrence in patients without hiatus hernia 33 . Free reflux is characterized by a fall in...

Antireflux barrier

Failure of the anti-reflux barrier is considered the most important factor in the pathogenesis of GERD. It is presently accepted that the two major elements that compose the anti-reflux barrier are the lower esophageal sphincter (LES) and the crural diaphragm. The LES is a thickened ring of tonically contracted circular smooth muscle that generates a 2-4 cm high pressure zone at the gastroesophageal junction and serves as a mechanical barrier between the stomach and the esophagus. The right...

Mechanisms of EGJ dysfunction in GERD

Reflux occurs with either intermittent or constant compromise of the EGJ high-pressure zone. An added element to EGJ competence is EGJ opening and the degree to which the EGJ opens during periods in which the high-pressure zone is compromised. Just as with the upper esophageal sphincter, it has become apparent that sphincter opening is not synonymous with sphincter relaxation. During swallowing, despite being neurally inhibited, the EGJ must open to facilitate the esophago-gastric flow of a...

Erosive esophagitis

Multiple studies have shown that only 30-40 of patients with typical reflux symptoms (i.e., heartburn, regurgitation) have evidence of erosive esophagitis (Fig. 1) on upper endoscopy whereas the other 60-70 of patients even with troublesome reflux symptoms have no clear-cut esophageal mucosal abnormalities 2 - 7 . Thus, overall endoscopy is an insensitive test for diagnosing reflux disease. However, if detected, erosive esophagitis has a good positive predictive value for the diagnosis of GERD...

Transient lower esophageal relaxations

Compelling evidence exists that transient LES relaxations are the most frequent mechanism for reflux during periods of normal LES pressure gt 10 mmHg . Transient LES relaxations occur independently of swallowing, are not accompanied by peristalsis, are accompanied by crural diaphragmatic inhibition, and persist for longer periods than do swallow-induced LES relaxations gt 10 seconds 29 , 30 . The dominant stimulus for transient LES relaxation is distension of the proximal stomach, not...

Prokinetic agents

This class of agents targets the underlying motility dysfunction that causes GERD. Specifically, they increase lower esophageal sphincter pressure, accelerate gastric clearance, stimulate esophageal peristalsis, and increase the amplitude of esophageal contractions 73 . Each of these agents bethenechol, metoclopra-mide, domperidone, and cisapride is effective in improving symptoms and healing erosions. They are especially useful in the presence of dyspeptic symptoms such as nausea, vomiting,...

Lower esophageal sphincter

Phrenoesophageal Membrane

The LES is a 3-4 cm segment of tonically contracted smooth muscle in the distal esophagus. Among normal individuals basal LES tone varies from 1030 mmHg relative to intragastric pressure and exhibits substantial temporal variation. Studies utilizing concurrent fluoroscopy and manometry, localize the proximal aspect of the EGJ high-pressure zone 1-1.5 cm proximal to the SCJ and the distal aspect extending about 2 cm distal to it 1 Fig. 1 . Anatomical studies suggest that the EGJ component distal...

Introduction

The understanding of the pathophysiology of gastroesophageal reflux disease GERD has evolved in the last decade primarily by recognizing the multitude of factors that contribute to the emergence of the disorder Fig. 1 . These factors may overlap in some patients and differ in others. GERD is primarily considered a motility disorder, because dysfunction of the anti-reflux barrier is still considered as a prerequisite for the development of the disease. However, recent investigation into symptom...

Histamine2receptor blockers H2Bs

This class of medications indirectly suppresses gastric acid and pepsin secretion by occupying Histamine2 receptors. They suppress basal, nocturnal, and penta-gastrin secretion, as well as acid secretion induced by insulin, meals, and sham feeding 74 . These medications have no effect on LES pressure or esophageal clearance 31 . Acid suppression is incomplete in response to meals, thus these are less effective in people with advanced reflux disease 35 . The H2B's reduce nocturnal acid by 85-94...