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Esophageal body motor response to reflux events:: Secondary peristalsis11Reprints are not available.
Abstract
The esophageal body is a major component of the antireflux mechanism. Disruption of esophageal peristalsis affects both volume clearance and delivery of swallowed saliva to the distal esophageal body. The esophageal body responds to reflux by an increase in primary peristalsis through stimulation of swallowing and secondary peristalsis through esophageal distension. Primary peristalsis is the most common motor event after reflux and accounts for up to 90% of initial and subsequent motor activity. Secondary peristalsis is uncommon but may be important during sleep when swallowing is relatively suppressed. Some patients with reflux disease, particularly those with severe esophagitis, exhibit impaired esophageal responses to reflux. It is likely that this impairment prolongs acid clearance and may also influence the proximal extent of the refluxate within the esophageal body.
... Even though there are multiple mechanisms that have been implicated in the pathophysiology of esophagitis, dysfunction of esophageal motility may be one of the most important ones. Prior studies have focused on the relationship between primary peristalsis (initiated by a voluntary swallow) and reflux burden, using measurements of esophageal manometry and pH-impedance [1][2][3][4][5][6][7][8] ; abnormal primary peristalsis is associated with a higher % time that the esophageal pH <4. 7,8 While primary peristalsis is well understood and recognized for its important role in bolus clearance, secondary peristalsis, which occurs non-volitionally in response to esophageal distension and is felt to be the critical mechanism for refluxate clearance, has only recently been investigated, with the introduction of the functional luminal imaging probe (EndoFLIP) testing. ...
... 7,8 While primary peristalsis is well understood and recognized for its important role in bolus clearance, secondary peristalsis, which occurs non-volitionally in response to esophageal distension and is felt to be the critical mechanism for refluxate clearance, has only recently been investigated, with the introduction of the functional luminal imaging probe (EndoFLIP) testing. [1][2][3][4][5][6][7][8][9][10] EndoFLIP employs impedance planimetry to measure luminal cross-sectional area and distensibility. With esophageal EndoFLIP balloon inflation, the esophagogastric junction (EGJ) relaxes, and secondary peristaltic waves are triggered in patients preserved esophageal neuromuscular integrity. ...
... The presence or absence of EGJ relaxation was recorded, and its relationship with the presence or absence of repetitive antegrade contractions (RACs) was determined. 7,8 EGJ relaxation was considered: (1) absent when there was no change in the EGJ diameter over baseline throughout the duration of secondary peristalsis; (2) partial when there was any increase in diameter associated with a RAC; or (3) complete when EGJ diameter was equivalent to the distal esophagus. 15 1. ...
Background
Disorders of primary peristalsis are associated with a higher percent time pH <4 in the esophagus suggesting poor acid clearance. However, there are no studies of secondary peristalsis and its relationship to microscopic or erosive esophagitis. The goal of this study was to determine the relationship between secondary peristalsis using functional luminal imaging probes (EndoFLIP) and the presence or absence of esophagitis.
Methods
We reviewed the endoscopic and EndoFLIP 2.0 tracings for 103 consecutive patients including those with a history of upper gastrointestinal surgery undergoing upper endoscopy. Esophagogastric junction (EGJ) distensibility and diameter, repetitive antegrade contraction (RACs) presence and frequency, and occlusive diameters were measured. Measurements were then compared between patients with and without microscopic and/or erosive esophagitis. Means were compared using t‐tests. Proportions were compared using Chi‐Squared analyses.
Key Results
One hundred and three patients were included (mean age: 14.4 + 6.4 years). Ten patients had erosive esophagitis and 28 patients had microscopic esophagitis. Erosive and microscopic esophagitis were associated with abnormal or absent of RACs (p < 0.001). Occlusive diameters were higher in patients with esophagitis compared to those without (p < 0.001). There was no relationship between EGJ distensibility and the presence of erosive or microscopic esophagitis (p = 0.4). The absence of RACs was the only independent predictor of esophagitis (erosive and microscopic), after controlling for age, proton pump inhibitors (PPI) use and EGJ distensibility (p < 0.001).
Conclusions & Inferences
Abnormal secondary peristalsis is associated with microscopic and gross esophagitis, suggesting that EndoFLIP should be part of the diagnostic algorithm for esophagitis.
... Median bolus clearance in the pooled analysis of all reflux was similar in GERD patients and controls (1613141516171819 vs 16Figure 4 . Distribution of nocturnal reflux in patients with gastroesophageal reflux disease with different degrees of acid exposure (AE). ...
... (B) Those with upright increased AE had predominance of acid events in the first 2 supine hours. (C) Patients with bi-positional increased AE had predominant acid reflux during the first 6 hours and weakly acidic reflux in the last 2 hours.1213141516171819 sec, P = 0.793). ...
... sec, P = 0.793). In GERD patients, acid reflux had longer bolus clearance compared to weakly acidic reflux (181213141516171819202122232425 vs 1611121314151617181920 sec, P ＜ 0.001). Acid clearance lasted significantly longer than bolus clearance in both patients (44 vs 181213141516171819202122232425 sec, P ＜ 0.001) and controls (37 vs 107891011121314 sec, P ＜ 0.005). ...
Impedance-pH monitoring allows detailed characterization of gastroesophageal reflux and esophageal activity associated with reflux. We assessed the characteristics of nocturnal reflux and esophageal activity preceding and following reflux.
Impedance-pH tracings from 11 healthy subjects and 76 patients with gastroesophageal reflux disease off acid-suppressive therapy were analyzed. Characteristics of nocturnal supine reflux, time distribution and esophageal activity seen on impedance at 2 minute intervals preceding and following reflux were described.
Patients had more nocturnal reflux events than healthy subjects (8 [4-12] vs 2 [1-5], P = 0.002), with lower proportion of weakly acidic reflux (57% [35-78] vs 80% [60-100], P = 0.044). Nocturnal reflux was mainly liquid (80%) and reached the proximal esophagus more often in patients (6% vs 0%, P = 0.047). Acid reflux predominated in the first 2 hours (66%) and weakly acidic reflux in the last 3 hours (70%) of the night. Most nocturnal reflux was preceded by aboral flows and cleared by short lasting volume clearance. In patients, prolonged chemical clearance was associated with less esophageal activity.
Nocturnal weakly acidic reflux is as common as acid reflux in patients with gastroesophageal reflux disease, and predominates later in the night. Impedance-pH can predict prolonged chemical clearance after nocturnal acid reflux.
... Manometry methods and techniques. The neonatal manometry techniques using esophageal provocation methods have been developed and validated by us (11,14,15,19). Briefly, the catheter assembly (Dentsleeve International, Mui Scientific, Mississauga, Ontario, Canada) was connected to the pneumohydraulic micromanometric water perfusion and recording systems via the resistors, pressure transducers (TNF-R disposable pressure transducers, MMS medical instruments, Dover, NH), and amplifiers (Solar modules, Solar-2, MMS medical instruments, Dover, NH). ...
... Both methods, station and sleeve pullthrough techniques, were adopted to ensure appropriate positioning (11,19). An array of catheters of the same architecture but of different lengths were used in accordance with infant weight (1.5-2.5 kg; 2.5-3.5 kg, and 3.5-5 kg). ...
... Manometry data analyses were done by two investigators who were blinded from the purpose of the study, and statistically significant concordance was reached. We have previously described the data analysis pertinent to the spontaneous PP (dry swallow), infusion-induced EDR (similar to PP waveforms), and SP (11,14,15,19). Spontaneous swallows or PP were identified as a fully propagated pharyngoesophageal sequence that begins in the pharynx and is associated with UES relaxation and propagation of the peristaltic wave front across the proximal, middle, and distal esophagus and accompanied by LESR (9). ...
We defined the sensory-motor characteristics of the lower esophageal sphincter relaxation (LESR) (stimulus threshold volume, response onset, and relaxation period, relaxation magnitude, nadir) during maturation in human neonates. We hypothesized that LESR kinetics differs during maturation and with peristaltic reflex type. Basal and adaptive esophageal motility testing was performed (N = 20 premature neonates) at 34.7 and 39.1 wk (time 1 and time 2). Effects of midesophageal provocation with graded stimuli (N = 1,267 stimuli, air and liquids) on LESR kinetics during esophagodeglutition response (EDR) and secondary peristalsis (SP) were analyzed by mixed models. Frequency of LESR with basal primary peristalsis were different during maturation (P = 0.03). During adaptive responses with maturation, 1) the frequencies of peristaltic reflexes and LESR were similar; 2) liquid stimuli resulted in a shorter LESR response latency and LESR nadir and greater LESR magnitude (all P < 0.05); 3) media differences were noted with LESR response latency (air vs. liquids, P < 0.02); and 4) infusion flow rate-LESR were different (P < 0.01 for air and liquids). Mechanistically, 1) frequency of LESR was greater during peristaltic reflexes at both times (vs. none, P < 0.0001); 2) LESR response latency, duration, and time to complete LESR were longer with EDR (all P < 0.05, vs. SP at time 2); and 3) graded stimulus volume LESR were different for air and liquids (P < 0.01). In conclusion, sensory-motor characteristics of LESR depend on the mechanosensitive properties of the stimulus (media, volume, flow), type of peristaltic reflex, and postnatal maturation. Maturation modulates an increased recruitment of inhibitory pathways that favor LESR.
... GERD is caused mainly by acid reflux due to abnormal relaxation of the LES and/or low activity of clearance in the esophageal body (DeMeester et al., 1979; Grossi et al., 2006; Grossi et al., 1998; Moayyedi & Talley, 2006; Nagahama et al., 2003). Gastroesophageal reflux itself occurs in almost all individuals to some degree (Holloway, 2000; Vandenplas & Hassall, 2002). The esophageal body is a major component of the antireflux mechanism. ...
... The esophageal body is a major component of the antireflux mechanism. Once reflux has occured, the reflux contents can be cleared by peristaltic sequences (Holloway, 2000). An intact peristaltic mechanism is essential for effective acid clearance. ...
... On the other hand, secondary peristalsis is defined as an adaptive reflex response to esophageal distention (2,(9)(10)(11), and has been described as early as 32-week PMA (2,11). Studies in the animal model suggest that this reflex is governed by visceral afferent and efferent innervation through the vagus (12,13). ...
... Similar comparison on secondary peristalsis between neonates and adults is difficult unless the experimental protocol is the same, including catheter design, infusion protocols, and locus of provocation. Furthermore, in adult studies (9,10), volition can influence the deglutition response. Reflexes in neonates are different in that these are truly reflexive, and that the development of the volitional aspects of reflexes is not well understood, and may not develop until later life. ...
The changes in esophageal propulsive characteristics during maturation are not known. Our aim was to define the effects of postnatal maturation on esophageal peristaltic characteristics in preterm human neonates. We tested the hypotheses that: (i) maturation modifies esophageal bolus propulsion characteristics, and (ii) the mechanistic characteristics differ between primary and secondary peristalsis.
Esophageal motility in 10 premature neonates (mean 27.5 weeks gestational age) was evaluated twice at 33.8 weeks (time 1, earlier study) and 39.2 weeks (time 2, later study) mean postmenstrual age. Esophageal manometry waveform characteristics (amplitude and duration, peristaltic velocity, and intrabolus pressure domains) were analyzed during spontaneous primary peristalsis and infusion-induced secondary peristalsis. Repeated-measures and unstructured variance-covariance or compound symmetry matrixes were used for statistical comparison. Values stated as least squares means+/-s.e.m. or percent.
A total of 200 primary peristalsis and 227 secondary peristalsis events were evaluated. Between time 1 and time 2: (i) proximal esophageal waveform amplitude increased (P<0.02), with primary peristalsis (38+/-6 vs. 48+/-7 mm Hg) and with secondary peristalsis (34+/-6 vs. 46+/-5 mm Hg); (ii) distal esophageal waveform amplitude was similar (P=NS), with primary peristalsis (42+/-4 vs. 43+/-4 mm Hg) and secondary peristalsis (29+/-3 vs. 32+/-4 mm Hg); (iii) proximal esophageal waveform onset to peak duration decreased (P=0.02) with primary (2.6+/-0.3 vs. 1.9+/-0.1 s, P<0.003) and with secondary peristalsis (2.2+/-0.2 vs. 1.8+/-0.1 s); (iv) distal esophageal waveform onset to peak duration decreased (P=0.01) with primary (2.4+/-0.3 vs. 1.8+/-0.1 s) and with secondary peristalsis (1.9+/-0.2 vs. 1.5+/-0.1 s); (v) effects of identical stimulus volume on intrabolus pressure were similar (P=NS); however, greater infusion volumes (2 vs. 1 ml) generated higher intrabolus pressure at both time 1 and time 2 (both Ps<0.05). Between primary and secondary peristalsis (mechanistic variable): (i) no differences were noted at either period, with proximal esophageal waveform amplitudes (P=NS); (ii) differences were noted with distal esophageal waveform amplitudes at each time period (P=0.0002); (iii) no differences were noted with both esophageal waveforms duration at either period (P=NS); (iv) peristaltic velocity was faster with secondary peristalsis than with primary peristalsis at either period (at earlier study, 7.9+/-1.4 vs. 2.5+/-1.4 cm/s and at later study 6.2+/-1.6 vs. 1.2+/-1.5 cm/s, both Ps<0.01).
In preterm neonates, longitudinal maturation modulates the characteristics of primary and secondary peristalsis. Differences in proximal striated muscle and distal smooth muscle activity during peristalsis are evident. Peristaltic velocity is faster with secondary peristalsis. These findings may represent maturation of central and peripheral neuromotor properties of esophageal bolus propulsion in healthy preterm human neonates.
... Many pathophysiologic theories have been postulated to explain carcinogenesis in achalasia (8). If food retention, bacterial fermentation, and mucosal inflammation are the main players for the development of squamous cell carcinoma (2,4), both surgical and endoscopic treatments aiming to reduce LES pressure are likely to increase the risk of GERD, Barrett's esophagus and, finally, esophageal adenocarcinoma (4,8,9); the impaired esophageal motility in achalasia could also lead to a reduced clearance of acid, thus contributing to the prolonged esophageal acid exposure after surgical or endoscopic disruption of LES (23)(24)(25). In our study, esophageal adenocarcinoma developed in patients who underwent surgical treatment; no cancer was observed in those who received endoscopic dilation; this observation is however limited by the small subgroup of patients receiving endoscopic treatment, and we cannot exclude that esophageal cancer develops also in patients who underwent endoscopic dilation. ...
Introduction:
Epidemiological studies assessing relative risk and incidence rate of esophageal cancer in patients with achalasia are scarce. We performed a long-term prospective cohort study to evaluate the risk of both squamous cell carcinoma and adenocarcinoma of the esophagus in these patients.
Methods:
Between 1973 and 2018, patients with primary achalasia were followed by the same protocol including upper endoscopy with esophageal biopsies. Standardized incidence ratios (SIRs) with 95% confidence interval (CI) were used to estimate the relative risk of esophageal cancer in patients with achalasia compared with the sex- and age-matched general population.
Results:
A cohort of 566 patients with achalasia (46% men, mean age at diagnosis: 48.1 years) was followed for a mean of 15.5 years since the diagnosis of achalasia. Overall, 20 patients (15 men) developed esophageal cancer: 15 squamous cell carcinoma and 5 adenocarcinoma. The risk of esophageal cancer was significantly greater than the general population (SIR 104.2, 95% CI 63.7-161), and this for both squamous cell carcinoma (SIR 126.9, 95% CI 71.0-209.3) and adenocarcinoma (SIR 110.2, 95% CI 35.8-257.2). The excess risk was higher in men than women. Annual incidence rate of esophageal cancer was only 0.24% and was higher for squamous cell carcinoma (0.18%) than adenocarcinoma (0.06%).
Discussion:
Patients with achalasia have an excess risk of developing both squamous cell carcinoma and adenocarcinoma of the esophagus; however, this prospective cohort study confirms that the annual incidence of esophageal cancer is rather low. These findings may have implications for endoscopic surveillance of patients with achalasia.
... 43 As secondary peristalsis might be important for acid clearance when voluntary swallowing is suppressed, 45 our work may support previous findings by suggesting careful use of GABA-B receptor agonists for treating reflux disease in terms of potentially negative impact on secondary peristalsis, especially in patients with significant erosive gastroesophageal reflux disease who are more vulnerable to have impaired secondary peristalsis. 5,46 Our study has some limitations that need to be acknowledged. First, although we have used current dose of baclofen 40 mg to detect the effects of GABA-B receptors activation in vivo for TRPV1 mediating heartburn perception and modulating secondary peristalsis, it remains to be determined whether such dosage is desirable to produce optimal effects for addressing our hypothesis. ...
Objectives:
Esophageal instillation of capsaicin enhances secondary peristalsis, but the γ-aminobutyric acid receptor type B (GABA-B) agonist baclofen inhibits secondary peristalsis. This study aimed to investigate whether baclofen could influence heartburn perception and secondary peristalsis subsequent to capsaicin infusion in healthy adults.
Methods:
Secondary peristalsis was performed by slow and rapid mid-esophagus air injections in 15 healthy subjects. Two different sessions including esophageal infusion of capsaicin-containing red pepper sauce (0.84 mg) following pre-treatment with placebo or baclofen were randomly performed to test the effects on heartburn perception and secondary peristalsis.
Results:
The intensity of heartburn symptom subsequent to capsaicin infusion was significantly greater after pre-treatment of baclofen as compared with the placebo (P=0.03). Baclofen significantly increased the threshold volume of secondary peristalsis to slow air injections subsequent to esophageal capsaicin infusion (P<0.001). Baclofen significantly increased the threshold volume of secondary peristalsis to rapid air injections subsequent to esophageal capsaicin infusion (P<0.01). The frequency of secondary peristalsis subsequent to capsaicin infusion was significantly decreased with baclofen as compared with the placebo (P<0.002). Baclofen had no effect on any of the peristaltic parameters of secondary peristalsis subsequent to capsaicin infusion.
Conclusions:
The GABA-B agonist baclofen appears to attenuate the esophagus to capsaicin-induced excitation of secondary peristalsis in healthy adults. Our study suggests the inhibitory modulation for GABA-B receptors on capsaicin-sensitive afferents mediating secondary peristalsis in human esophagus.
... Secondary peristalsis is triggered by esophageal distension when food, liquid or air is retained in the esophagus after a failed primary peristaltic event or a reflux from the stomach [1] . It is important to maintain an empty esophagus by clearing the bulk of the volume of the refluxate after a reflux event [2] . ...
AIM
To determine whether capsaicin infusion could influence heartburn perception and secondary peristalsis in patients with gastroesophageal reflux disease (GERD).
METHODS
Secondary peristalsis was performed with slow and rapid mid-esophageal injections of air in 10 patients with GERD. In a first protocol, saline and capsaicin-containing red pepper sauce infusions were randomly performed, whereas 2 consecutive sessions of capsaicin-containing red pepper sauce infusions were performed in a second protocol. Tested solutions including 5 mL of red pepper sauce diluted with 15 mL of saline and 20 mL of 0.9% saline were infused into the mid-esophagus via the manometric catheter at a rate of 10 mL/min with a randomized and double-blind fashion. During each study protocol, perception of heartburn, threshold volumes and peristaltic parameters for secondary peristalsis were analyzed and compared between different stimuli.
RESULTS
Infusion of capsaicin significantly increased heartburn perception in patients with GERD (P < 0.001), whereas repeated capsaicin infusion significantly reduced heartburn perception (P = 0.003). Acute capsaicin infusion decreased threshold volume of secondary peristalsis (P = 0.001) and increased its frequency (P = 0.01) during rapid air injection. The prevalence of GERD patients with successive secondary peristalsis during slow air injection significantly increased after capsaicin infusion (P = 0.001). Repeated capsaicin infusion increased threshold volume of secondary peristalsis (P = 0.002) and reduced the frequency of secondary peristalsis (P = 0.02) during rapid air injection.
CONCLUSION
Acute esophageal exposure to capsaicin enhances heartburn sensation and promotes secondary peristalsis in gastroesophageal reflux disease, but repetitive capsaicin infusion reverses these effects.
... Since secondary peristalsis appears to be important during sleep states when salivation and primary peristalsis are suppressed; 24 it is expected that prucalopride has potential clinical utility in improving nocturnal acid reflux because of its benefits on decreasing acid reflux 11 and promoting secondary peristalsis, as shown in this work. Moreover, since it has been demonstrated that impaired secondary peristalsis occurs in patients with gastro-esophageal reflux disease and was found more in those with severe esophagitis or concomitant ineffective motility, [25][26][27] current findings indicate that prucalopride is theoretically helpful in improving esophageal hypomotility in patients with complicated gastroesophageal reflux disease. This notion needs to be further confirmed in gastro-esophageal reflux disease patients with significant esophageal hypomotility. ...
Objectives
Prucalopride, a high-affinity 5-hydroxytrypatamine 4 (5-HT4) receptors agonist, has been shown to improve colon motility in adults. Secondary peristalsis helps the clearance of retained food bolus and refluxate from the esophagus, but the effects of prucalopride on esophageal secondary peristalsis are unknown. We aimed to assess the effects of prucalopride on distension-induced secondary peristalsis in healthy adults.
Methods
Two separate sessions with prucalopride and placebo were performed in 11 healthy adults to test the effects on secondary peristalsis. Secondary peristalsis was performed with slow and rapid mid-esophageal injections of air after a baseline recording of esophageal motility.
Results
Prucalopride significantly decreased the threshold volume to generate secondary peristalsis during slow air injection (9.8±1.4 vs. 14.4±0.9 ml, P=0.005) and rapid air injection (3.9±0.3 vs. 5.2±0.4 ml, P=0.008). Secondary peristalsis was generated more frequently after application of prucalopride (80% (70–100%) vs. 70% (60–73%), P=0.01). Prucalopride increased the wave amplitude of distal esophagus during slow air injection (147.9±28.5 vs. 104.2±16.8 mm Hg, P=0.048) and rapid air injection (128.0±13.3 vs. 105.7±12.3 mm Hg, P=0.016). Primary peristaltic amplitudes were also significantly increased by the application of prucalopride.
Conclusions
Acute administration of prucalopride enhances mechanosensitivity of distension-induced secondary peristalsis and promotes esophageal contractility in healthy adults. Whether prucalopride could be a therapeutic option for the treatment of subjects with esophageal hypomotility needs further study.
... 19,60 Due to the high prevalence of HH in BE 61 and common large-volume as well as repeated reflux episodes (re-reflux) in HH patients, 24 ambulatory clearance times may be artifactually prolonged. 18,62 Thus, an ambulatory pH measurement showing increased acid exposure in BE cannot per se be considered evidence that esophageal acid clearance function is impaired. It may merely represent repeated and/or large-volume reflux episodes. ...
Background/Aims
Impaired esophageal acid clearance may be a contributing factor in the pathogenesis of Barrett’s esophagus. However, few studies have measured acid clearance as such in these patients. In this explorative, cross-sectional study, we aimed to compare esophageal acid clearance and swallowing rate in patients with Barrett’s esophagus to that in healthy controls.
Methods
A total of 26 patients with histology-confirmed Barrett’s esophagus and 12 healthy controls underwent (1) upper endoscopy, (2) an acid clearance test using a pH-impedance probe under controlled conditions including controlled and random swallowing, and (3) an ambulatory pH-impedance measurement.
Results
Compared with controls and when swallowing randomly, patients cleared acid 46% faster (P = 0.008). Furthermore, patients swallowed 60% more frequently (mean swallows/minute: 1.90 ± 0.74 vs 1.19 ± 0.58; P = 0.005), and acid clearance time decreased with greater random swallowing rate (P < 0.001). Swallowing rate increased with lower distal esophageal baseline impedance (P = 0.014). Ambulatory acid exposure was greater in patients (P = 0.033), but clearance times assessed from the ambulatory pH-measurement and acid clearance test were not correlated (all P > 0.3).
Conclusions
More frequent swallowing and thus faster acid clearance in Barrett’s esophagus may constitute a protective reflex due to impaired mucosal integrity and possibly acid hypersensitivity. Despite these reinforced mechanisms, acid clearance ability seems to be overthrown by repeated, retrograde acid reflux, thus resulting in increased esophageal acid exposure and consequently mucosal changes.
... We speculate that this lower BHATc could be due to more effective and better organized peristalsis during suction. Indeed, the transport of swallowed milk into the stomach is performed principally by primary peristalsis [27,28], whereas in the postprandial period secondary peristalsis dominates; it arises in the esophagus triggered by the stimulation of esophageal sensory receptors due to the presence of bolus residues not completely eliminated by the primary peristaltic wave, or by GER, with the purpose of clearing these residues [29]. ...
Purpose:
The aim of this study was to evaluate bolus transit during esophageal swallow (ES) and gastroesophageal reflux (GER) events and to investigate the relationship between the characteristics of ES and GER events in a population of term and preterm newborns with symptoms of gastroesophageal reflux disease (GERD).
Methods:
The study population consisted of term and preterm newborns referred to combined multichannel intraluminal impedance (MII) and pH monitoring for GERD symptoms. The frequency and characteristics of ES and GER events were assessed by two independent investigators. Statistical significance was set at p<0.05.
Results:
Fifty-four newborns (23 preterm) were included in the analyses. Median bolus head advancing time corrected for esophageal length (BHATc) was shorter during mealtime than during the postprandial period (median, interquartile range): 0.20 (0.15-0.29) s/cm vs. 0.47 (0.39-0.64) s/cm, p<0.001. Median bolus presence time (BPT) was prolonged during mealtime: 4.71(3.49-6.27) s vs. 2.66 (1.82-3.73) s, p<0.001. Higher BHATc (p=0.03) and prolonged BPT (p<0.001) were observed in preterm newborns during the postprandial period. A significant positive correlation between BHATc and bolus clearance time was also observed (ρ=0.33, p=0.016).
Conclusion:
The analysis of ES and GER events at the same time by MII provides useful information to better understand the physiopathology of GERD. In particular, the analysis of BHATc during the postprandial period could help clinicians identify newborns with prolonged esophageal clearance time due to impaired esophageal motility, which could allow for more accurate recommendations regarding further tests and treatment.
... It is mainly important during sleep, when swallowing is impaired. 4 The esophagus clears away the regurgitated contents through its motor activity (volume clearance). The produced bicarbonate and saliva play a role in neutralizing the regurgitated acidic fluid (acid clearance). ...
... O bolo é levado para o estômago a partir dos movimentos peristálticos do esôfago (25) . O esfíncter esofágico inferior, localizado na porção caudal do esôfago, se fecha para impedir o refluxo do conteúdo estomacal (26) . ...
Cricopharyngeal myotomy is a surgical procedure that might be indicated to patients with oropharyngeal dysphagia that, in general, are characterized by a motor impairment limited to the pharyngeal phase of swallowing, cricopharyngeal incoordination or incomplete relaxation of the Upper Esophageal Sphincter (UES). Indication of the myotomy, however, have been discussed and applied in many cases, with no effect on the improvement of deglutition dynamics. The aim of this study was to verify the criteria of indication and efficacy of cricopharingeal myotomy, based on studies of deglutition physiology in patients with oropharyngeal dysphagia. A literature review about this procedure and the description of its results on deglutition dynamics was carried out. Results showed that the best indicators of a well-succeeded myotomy are: efficient oral phase and good laryngeal elevation during deglutition. Therefore, an adequate indication of cricopharyngeal myotomy must consider not only the pharyngeal phase and the isolated functioning of the UES, but also the coordination and the relationship between the oral and the pharyngeal phases of deglutition.
... Em indivíduos normais, a resposta inicial ao refluxo ácido é usualmente o peristaltismo primário, provavelmente devido à alta taxa de deglutições no estado desperto e pelo estímulo à deglutição pelo refluxo ácido. O peristaltismo secundário é menos comum, tendo papel importante durante o decúbito e o sono, provavelmente pela supressão da salivação e deglutição durante o sono (12) . As deglutições de saliva provocam menor amplitude de contração do que as deglutições com algum volume de líquido ou sólido (34) , portanto com maior possibilidade de serem ineficazes. ...
Background - During sleep the gastrointestinal system function is markedly reduced most of the time. Objectives - In this revision we described the effect of sleep on the digestive system. Salivation, swallowing rate, upper esophageal sphincter pressure and number of primary esophageal contractions have all been shown to be reduced during sleep. Data sources - Gastric emptying is slow during sleep but the REM sleep is associated with faster gastric emptying. During the night we have a more regular intestinal motility than during the day. During sleep, phase 11 of the migrating motor complex cycle is virtually absent, both during diurnal or nocturnal sleep. The nocturnal velocity of migrating motor complex propagation in the proximal small bowel is slower than the diurnal velocity. The colon has a decrease in tonus and contractions. The anal canal pressure is lower and rectum activity is higher during sleep than during the awake state, but the anal pressure is still higher than the rectum pressure and the rectum contractions are most frequently retrograde. Data synthesis - Transient lower esophageal sphincter relaxation is the most frequent cause of gastroesophageal reflux. The frequency of this transient relaxation is very low during sleep. Gastroesophageal reflux during sleep is more frequently associated with a low lower esophageal sphincter pressure. Conclusions - In this situation the disease is worse because the patient is in the supine position, so gravity does not help the acid esophageal clearance, salivation is decreased and the primary esophageal contraction is not frequent, a fact causing a prolongation of acid clearance during sleep. The right lateral position during sleep causes more reflux episodes than the left lateral position. The gastroesophageal reflux may be associated with nocturnal wheezing, chronic nocturnal cough and sleep apnea.
... The presence of reflux within the oesophagus stimulates a peristaltic wave which clears the refluxate back into the stomach [23]. Secondary peristalsis may also be stimulated and play a role, particularly during sleep when swallowing is relatively suppressed [24,25]. Swallowing also delivers saliva into the oesophagus and its bicarbonate content (pH 7.8-8.0) ...
... O bolo é levado para o estômago a partir dos movimentos peristálticos do esôfago (25) . O esfíncter esofágico inferior, localizado na porção caudal do esôfago, se fecha para impedir o refluxo do conteúdo estomacal (26) . ...
A miotomia do cricofaríngeo é um procedimento cirúrgico que pode ser indicado para pacientes com disfagia orofaríngea que, em geral, caracterize-se por distúrbio motor limitado à fase faríngea da deglutição, incoordenação cricofaríngea ou relaxamento incompleto do Esfíncter Esofágico Superior (EES). A indicação da miotomia, porém, tem sido discutida e aplicada em muitos casos, sem efeito na melhora da dinâmica da deglutição. O objetivo deste estudo foi verificar os critérios de indicação e eficácia da miotomia do cricofaríngeo, com base nos estudos da fisiologia da deglutição em pacientes com disfagia orofaríngea. Realizou-se, então, uma revisão da literatura sobre este procedimento e a descrição de seus resultados na dinâmica da deglutição. Os resultados demonstraram que os melhores indicadores para uma miotomia bem sucedida são: fase oral eficiente e boa elevação laríngea durante a deglutição. Assim, para uma adequada indicação da miotomia do cricofaríngeo, não se deve avaliar apenas a fase faríngea e o funcionamento isolado do EES, mas a coordenação e relação entre as fases oral e faríngea da deglutição.
... This hypothesis is in line with our findings as less severe patients are managed with more conservative procedures than surgery and the risk of EAC was higher among unoperated patients. c) Given the importance of acid clearance in the development of EAC (167)(168)(169), it may be hypothesized that even a minor reflux in a dysmotility-stricken esophagus increases the risk of Barrett's esophagus and EAC. d) It has been hypothesized that chronic inflammation caused by fermentation of retained food to lactic acid within the esophagus (46, 170) may lead to metaplastic transformation of the squamous mucosa to Barrett's esophagus. ...
... This has particular relevance as it is known that impaired secondary peristalsis occurs in patients with GERD and in those with severe esophagitis. 6,43 In summary, mosapride enhances esophageal mechanosensitivity by rapid air distension and increases distension-induced esophageal secondary peristaltic activity in healthy volunteers. These data provide supportive evidence for the involvement of 5-HT 4 receptor agonist and its prokinetic effect in the modulation of distension-induced esophageal secondary peristalsis in humans. ...
Secondary peristalsis is important for the clearance of refluxate or retained food bolus from the esophagus. Mosapride is a prokinetic agent that enhances GI motility by stimulating 5-hydroxytrypatamine(4) (5-HT(4) ) receptors, but its effects on secondary peristalsis are yet unclear in humans. We aimed to investigate the effect of a 5-HT(4) agonist mosapride on esophageal distension-induced secondary peristalsis in normal subjects.
After a baseline recording esophageal motility, secondary peristalsis was generated by slow and rapid mid-esophageal injections of air in 15 healthy subjects. Two separate sessions with 40mg oral mosapride or placebo were randomly performed to test their effects on esophageal secondary peristalsis.
Mosapride decreased the threshold volume for triggering secondary peristalsis during rapid air distension (4.5±0.3 vs 5.3±0.4mL; P=0.04) but not slow air distension (14.3±1.2 vs 13.3±1.3mL; P=0.41). Secondary peristalsis was triggered more frequently in response to rapid air distension after application of mosapride [100% (90-100%) vs 90% (80-100%); P=0.02]. Mosapride significantly increased pressure wave amplitudes of secondary peristalsis during slow (135.4±13.8 vs 105.0±12.9mmHg; P=0.001) and rapid air distensions (124.0±11.6 vs 95.9±14.0mmHg; P=0.002).
Mosapride enhances sensitivity to distension-induced secondary peristalsis and facilitates secondary peristaltic contractility. These data provide an evidence for modulation of esophageal secondary peristalsis by the 5-HT(4) agonist mosapride, as well support for its clinical utility.
... Secondary peristalsis is one mechanism by which refluxate is cleared from the esophagus. 27,28 Our finding of an attenuated secondary peristaltic response to rapid esophageal air distension in patients with laryngitis could conceivably constitute another risk factor for proximal esophageal and pharyngeal acid exposure. However, any etiological link to laryngitis remains speculative. ...
Inappropriate or excessive, non-swallow related, reflexive relaxation of the upper esophageal sphincter (UES) in response to esophageal distension may be the principal mechanism permitting retrograde trans-sphincteric flow during acid regurgitation. The neural pathways mediating reflexive UES relaxation in the human have received little attention. Patients with laryngitis demonstrate an increased acid reflux in the proximal esophagus. Such events, combined with an increased tendency for UES relaxation, might precipitate regurgitation into the pharynx. The aim was to determine whether the esophago-UES relaxation reflex induced by rapid esophageal distension is upregulated in patients with posterior laryngitis.
In 21 healthy volunteers and 14 patients with posterior laryngitis, UES responses to rapid air insufflation were examined. UES responses were monitored with perfused manometry catheter with a oval sleeve sensor.
The probability of triggering UES relaxation in response to the rapid esophageal air distension, for all volumes of insufflation, was higher in laryngitis (45%) than in health (17%). The minimum distension volume required to elicit an UES relaxation response was significantly lower in laryngitis patients when compared with controls. Patients who demonstrated a laryngoscopic response to a trial of omeprazole, were less likely to generate a distension-induced UES contractile response (5%) than patients who did not respond (23%).
The threshold for esophageal distension-induced UES relaxation is reduced in patients with laryngitis when compared with controls. This finding supports the hypothesis that in this population, a hypersensitive belch-like response may be one contributory mechanism of regurgitation when triggered by an abrupt spontaneous gastro-esophageal reflux event.
... Impairment of esophageal body contraction, as manifested by reduced contraction amplitude and aperistalsis, is a frequent finding in patients with ERD. Twenty percent of individuals with moderate esophagitis and 50% of patients with severe esophagitis show aperistalsis and hypotensive contractions [19] . ...
To analyze manometric abnormalities in patients with isolated distal reflux and compare these findings in patients with erosive and non-erosive disease.
Five hundred and fifty patients who presented to the outpatient clinic of Turkiye Yuksek Ihtisas Hospital with gastroesophageal reflux disease-like symptoms were enrolled. Each individual was evaluated with esophageal manometry, 24-h ambulatory pH monitoring, and upper gastrointestinal endoscopy. Manometric findings for the patients with isolated distal reflux were compared to findings in controls who were free of reflux disorders or hypersensitive esophagus. Findings for isolated distal reflux patients with and without erosive reflux disease were also compared.
Of the 550 subjects enrolled, 97 (17.6%, mean age 48 years) had isolated distal reflux and 100 had no abnormalities on ambulatory pH monitoring (control group, mean age 45 years). There were no significant differences between the isolated distal reflux group and control group with respect to age, body mass index, and esophageal body contraction amplitude (EBCA). Mean lower esophageal sphincter pressure was significantly higher in the control group (12.7 +/- 10.3 mmHg vs 9.6 +/- 7.4 mmHg, P = 0.01). Fifty-five (56.7%) of the 97 patients with isolated distal reflux had erosive reflux disease. There were no statistical differences between the erosive reflux disease and non-erosive reflux disease subgroups with respect to mean EBCA, lower esophageal sphincter pressure, or DeMeester score. However, 13% of patients with gastroesophageal reflux disease had distal wave amplitudes < or = 30 mmHg, whereas none of the patients with non-erosive reflux disease had distal wave amplitudes in this low category.
Patients with erosive and non-erosive disease present with similar manometric abnormalities. The only striking difference is the observation of very low EBCA exclusively in patients with erosive disease.
... Em indivíduos normais, a resposta inicial ao refluxo ácido é usualmente o peristaltismo primário, provavelmente devido à alta taxa de deglutições no estado desperto e pelo estímulo à deglutição pelo refluxo ácido. O peristaltismo secundário é menos comum, tendo papel importante durante o decúbito e o sono, provavelmente pela supressão da salivação e deglutição durante o sono (12) . As deglutições de saliva provocam menor amplitude de contração do que as deglutições com algum volume de líquido ou sólido (34) , portanto com maior possibilidade de serem ineficazes. ...
Background - During sleep the gastrointestinal system function is markedly reduced most of the time. Objectives - In this revision we described the effect of sleep on the digestive system. Salivation, swallowing rate, upper esophageal sphincter pressure and number of primary esophageal contractions have all been shown to be reduced during sleep. Data sources - Gastric emptying is slow during sleep but the REM sleep is associated with faster gastric emptying. During the night we have a more regular intestinal motility than during the day. During sleep, phase II of the migrating motor complex cycle is virtually absent, both during diurnal or nocturnal sleep. The nocturnal velocity of migrating motor complex propagation in the proximal small bowel is slower than the diurnal velocity. The colon has a decrease in tonus and contractions. The anal canal pressure is lower and rectum activity is higher during sleep than during the awake state, but the anal pressure is still higher than the rectum pressure and the rectum contractions are most frequently retrograde. Data synthesis - Transient lower esophageal sphincter relaxation is the most frequent cause of gastroesophageal reflux. The frequency of this transient relaxation is very low during sleep. Gastroesophageal reflux during sleep is more frequently associated with a low lower esophageal sphincter pressure. Conclusions - In this situation the disease is worse because the patient is in the supine position, so gravity does not help the acid esophageal clearance, salivation is decreased and the primary esophageal contraction is not frequent, a fact causing a prolongation of acid clearance during sleep. The right lateral position during sleep causes more reflux episodes than the left lateral position. The gastroesophageal reflux may be associated with nocturnal wheezing, chronic nocturnal cough and sleep apnea.
Background/Aims
Activation of the cold receptor, transient receptor potential melastatin 8 (TRPM8) by menthol inhibits esophageal secondary peristalsis in healthy adults. Ineffective esophageal motility (IEM) is common. This study is to evaluate the effects of acute infusion of menthol on esophageal peristalsis in patients with IEM.
Methods
Twenty patients with IEM (males 11, mean age 36) were studied for esophageal peristalsis using high-resolution manometry. All participant had primary peristalsis performed with 10 water swallows and secondary peristalsis generated with 10 rapid air injections of 20 mL via mid-esophageal infusion port. Two different sessions by randomly performing acute administration of placebo or menthol (3 mM) were used for testing their effects on esophageal peristalsis.
Results
Menthol infusion had no effects on distal contractile integral (P = 0.471), distal latency (P = 0.58), or complete peristalsis (P = 0.251). Menthol infusion did not change basal lower esophageal sphincter pressure (P = 0.321), esophagogastric junction contractile integral (P = 0.758), or integrated relaxation pressure (P = 0.375) of primary peristalsis, but reduced upper esophageal sphincter pressure (P = 0.037). Infusion of menthol significantly reduced the frequency of secondary peristalsis for air injects of 20 mL (P = 0.002), but did not affect distal contractile integral of secondary peristalsis for air injections of 20 mL.
Conclusion
This work has suggested that activation of TRPM8 by menthol can attenuate mechanosensitivity of secondary peristalsis in response to rapid air distension regardless of the presence of IEM.
Gastroesophageal reflux is a physiological phenomenon, occurring with different severity and duration in different individuals. Reflux disease occurs when this normal event results in the occurrence of symptoms/signs or complications. The pathophysiology of gastroesophageal reflux is complex and diverse, since it is influenced by factors that are genetic, environmental (e.g., diet smoking), anatomic, hormonal, and neurogenic. However, many mechanisms remain incompletely understood. Future research should focus on a better understanding of the physiology of the upper and lower esophageal sphincters, and of gastric motility. The afferent and efferent neural pathways and neuropharmacologic mediators of transient lower esophageal sphincter relaxations and gastric dysmotility require further study. The role of anatomic malformations such as hiatal hernia in children has been underestimated.
While therapeutic possibilities are greater in number and largely improved, the outcomes of some treatments are far from satisfactory in many cases. In addition to development of new forms of treatment, research should address better use of currently available medical and surgical treatments.
Background/aims
The present study investigates manometrically in healthy piglets whether esophageal clearance after distension with different volumes of acid is volume‐dependent.
Methods
Sedated, non‐intubated piglets (n = 22) underwent stationary manometry of the esophagus with a 4‐probe perfused assembly after successive injection of 1, 2, and 3 mL of saline and acid. Simultaneous pH metering allowed assessment of acid clearance. Wave features and clearance times after saline and acid were compared by paired non‐parametric tests and Friedman analysis of variance. The linearity of the relationships between the clearance times and the volumes of acid infused were tested after square root transformations by one‐way ANOVA repeated measures. The significance level was set at P < 0.05.
Results
The motor response was identical after distension with saline and acid except for the largest amount of acid used, which elicited more waves during the first 5 minutes after infusion. Time elapsed until regaining pH4 was longer after higher amounts of acid, but not significantly, whereas that necessary to regain baseline pH was significantly longer after such challenge. Esophageal motility was practically identical after 1 and 2 mL of acid, but it was slightly less effective in the first minute after the 3 mL challenge. There was a linear correlation between clearance times and volumes of acid infused.
Conclusions
Up to a certain volume, the motor responses of the healthy esophagus to distension with neutral or acid fluids were similar. Acid clearance was more a function of the amount of acid present than of the motor response elicited by its presence. Only when the amount of acid was large, esophageal motor response was worse than that elicited after equivalent volumes of neutral fluid. The present evidence suggests that long episodes of reflux in pH tracings might reflect large volumes of refluxate as well as disturbed motor function.
Background and Aim
Prucalopride, a high‐affinity 5‐hydroxytryptamine 4 receptor agonist, promotes esophageal peristalsis, while phosphodiesterase type 5 inhibitor sildenafil inhibits esophageal peristalsis. The present study was aimed to evaluate whether prucalopride would augment esophageal peristalsis subsequent to the application of sildenafil.
Methods
Seventeen healthy adults underwent high‐resolution manometry by a catheter with one injection port located in the mid‐esophagus. Secondary peristalsis was assessed by rapid air injections after water swallows. Two sessions were randomly performed including acute administration of sildenafil 50 mg after pretreatment with prucalopride or the placebo.
Results
The frequency of primary peristalsis subsequent to the administration of sildenafil was significantly increased by prucalopride (P = 0.02). Prucalopride also significantly increased distal contractile integral of primary peristalsis subsequent to the administration of sildenafil (P = 0.03). No difference in the frequency of secondary peristalsis subsequent to the administration of sildenafil for air injects of 10 mL (P = 0.14) or 20 mL (P = 0.21) was found between prucalopride and placebo. Prucalopride did not change distal contractile integral of secondary peristalsis subsequent to the administration of sildenafil for air injections of 10 mL (P = 0.09) or 20 mL (P = 0.12).
Conclusions
Prucalopride modulates sildenafil‐induced inhibition of primary peristalsis by increasing its effectiveness and peristaltic wave amplitude. Our findings suggest that activation of 5‐hydroxytryptamine 4 receptors plays a role in mediating sildenafil‐induced inhibition of esophageal primary peristalsis rather than secondary peristalsis.
Background and aim:
Acute esophageal acid infusion promotes distension-induced secondary peristalsis. The gamma-aminobutyric acid receptor type B (GABA-B) receptors activation inhibits secondary peristalsis. This study aimed to test the hypothesis whether acid excitation of secondary peristalsis can be influenced by baclofen.
Methods:
Secondary peristalsis was performed with intra-esophageal slow and rapid air injections in 13 healthy subjects. Direct esophageal infusion of 0.1N HCl following pretreatment with placebo or baclofen was randomly performed at least one week apart. Symptom intensity, distension thresholds and peristaltic parameters were determined and compared between each study protocol.
Results:
The intensity of heartburn symptom in response to esophageal acid infusion was significantly greater with baclofen than the placebo (P = 0.002). The threshold volume of secondary peristalsis during slow air injections in response to acid infusion was significantly greater with baclofen than the placebo (P = 0.001). Baclofen significantly increased the threshold volume of secondary peristalsis during rapid air injections in response to acid infusion (P = 0.001). The frequency of secondary peristalsis in response to acid infusion was significantly decreased by baclofen as compared to the placebo (P = 0.001). Baclofen significantly decreased peristaltic amplitudes in response to acid infusion during rapid air injections (P = 0.007).
Conclusions:
GABA-B agonist baclofen inhibits acid excitation of secondary peristalsis in human esophagus, which is probably mediated by both muscular and mucosal mechanoreceptors. This work supports the evidence of potential involvement of GABA-B receptors in negative modulation of acid excitation of esophageal perception as well as secondary peristalsis.
Gastroesophageal reflux (GER) occurs frequently in infants, generally at its worst at 4 months of age, with approximately two-thirds of infants spitting up daily. GER typically improves after 7 months of age, with only ∼5% of infants continuing to have reflux at 1 year of age. The diagnosis can often be made based on clinical symptoms. Upper GI (UGI) study has low sensitivity and specificity and should not be ordered as a diagnostic test for reflux. UGI study is best for evaluating other anatomic causes of vomiting. GER becomes problematic gastroesophageal reflux disease (GERD) when complications are present, including feeding difficulties and poor weight gain. Conservative treatment and thickened formula can be helpful for treating GERD. Proton pump inhibitors (PPIs) are frequently prescribed for treating reflux. However, studies do not show a definite benefit in infants, and there are potential side effects. Older children with GERD may present with regurgitation, heartburn, chest discomfort, dysphagia, abdominal pain, vomiting, poor appetite, or poor weight gain. Upper endoscopy is considered for children with concerning symptoms, persistent symptoms despite treatment, and relapse of symptoms after treatment. Other esophageal disorders can have a similar clinical presentation as GERD, notably eosinophilic esophagitis (EoE). EoE is a chronic immune-mediated disorder of the esophagus, which may present as dysphagia, food impaction, heartburn, vomiting, abdominal pain, feeding difficulties, or failure to thrive. Diagnosis is made histologically by the presence of esophageal eosinophilia on endoscopic biopsies in the correct clinical setting.
Backgrounds/aim:
Ineffective esophageal motility (IEM) is associated with gastroesophageal reflux disease (GERD). Secondary peristalsis contributes to esophageal clearance. Prucalopride promotes secondary peristalsis by stimulating 5-hydroxytrypatamine 4 receptors in the esophagus. We aimed to determine whether prucalopride would augment secondary peristalsis in GERD patients with IEM.
Methods:
After a baseline recording of primary peristalsis, secondary peristalsis was stimulated by slow and rapid mid-esophageal injections of air in 15 patients with IEM. Two separate sessions with 4 mg oral prucalopride or placebo were randomly performed.
Results:
Prucalopride significantly increased primary peristaltic wave amplitude (68.1 ± 10.0 vs. 55.5 ± 8.8 mmHg, P = 0.02). The threshold volume for triggering secondary peristalsis was significantly decreased by prucalopride during slow (9.3 ± 0.8 vs. 12.0 ± 0.8 mL; P = 0.04) and rapid air injection (4.9 ± 0.3 vs. 7.1 ± 0.1 mL; P = 0.01). Secondary peristalsis was triggered more frequently after application of prucalopride (55% [43-70%]) than placebo (45% [33-50%]) (P = 0.008). Prucalopride didn't change pressure wave amplitudes during slow air injection (84.6 ± 8.1 vs. 57.4 ± 13.8 mmHg; P = 0.19) or pressure wave amplitudes during rapid air injection (84.2 ± 8.6 vs. 69.5 ± 12.9 mmHg; P = 0.09).
Conclusions:
Prucalopride enhances primary peristalsis as well as mechanosensitivity of secondary peristalsis with limited impact on secondary peristaltic activities in IEM patients. Our study suggests that prucalopride appears to be useful in augmenting secondary peristalsis in patients with IEM only via sensory modulation of esophageal secondary peristalsis.
Gastroesophageal reflux is a normal physiologic process, with multiple mechanisms in place to prevent physiologic reflux from becoming pathologic. One such mechanism is esophageal clearance. Esophageal clearance is composed of two distinct phases: volume clearance and chemical clearance. Volume clearance utilizes swallowing and esophageal peristalsis to empty the esophagus of reflux bolus and virtually all acid. Chemical clearance neutralizes the residual acid film by saliva, either swallowed or secreted by the esophagus. Combined pH-multichannel intraluminal impedance is the best technique to measure both phases of clearance. Normal values for children have been established. If either phase of esophageal clearance is prolonged, the esophagus experiences increased acid exposure, and this can result in secondary complications. There are physiologic and disease states which can impact either or both of the clearance phases. They do so by impacting the swallow, esophageal peristalsis, esophageal motility, and composition or quantity of saliva. As a result, these patients are predisposed to gastroesophageal reflux disease.
Gastro-oesophageal reflux is an extremely common paediatric problem, and its pathogenesis is complex and multifactorial involving anatomic, hormonal, environmental, and genetic factors (Fig. 72.1). The difference between physiological reflux (GER) and gastro-oesophageal reflux disease (GERD) is often blurred by the anxiety engendered in parents, particularly first-time parents, by symptoms such as vomiting and irritability in young infants.
Esophageal motility testing evaluates the two most important physiologic functions of the esophagus: to provide appropriate muscle response, including two functional sphincters coordinated with the contraction of muscle from esophageal body, and to conduct food bolus from the pharynx into the stomach. Tests used to access esophageal contraction include stationary and prolonged esophageal manometry and, most recently, high-resolution manometry (HRM). Tests to evaluate bolus transmission include videocineroentgenography, esophageal transit scintigraphy, esophageal impedance monitoring, and, recently, esophageal motility testing, which consists and concomitant monitoring of the pressure profile and the impedance tracings.
Objective:
Sleep disturbance is common in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis is important for clearance of the refluxate from the esophagus. We aimed to test the hypothesis whether secondary peristalsis is impaired in GERD patients with sleep disturbance.
Methods:
Secondary peristalsis was stimulated with slow and rapid air injections into mid-esophagus in 8 age-matched health controls and 41 patients with GERD. Sleep disturbance was assessed by the Pittsburg Sleep Quality Index (PSQI). Objective sleep measures were assessed by ambulatory actigraphy.
Results:
The threshold volume for inducing secondary peristalsis during slow air injection was significantly higher in GERD patients with sleep disturbance than healthy controls (14.3 ± 1.2 vs. 8.9 ± 0.5 mL, p < 0.05). GERD patients with sleep disturbance had higher threshold volume of secondary peristalsis during rapid air injection than GERD patients without sleep disturbance (5.1 ± 0.4 vs. 3.9 ± 0.2 mL, p < 0.05) and healthy controls (5.1 ± 0.4 vs. 3.6 ± 0.2 mL, p < 0.05). There was a negative correlation between PSQI score and peristaltic frequency during rapid air injection (r = -0.39, p = 0.01). Secondary peristaltic amplitude during rapid air injection was negatively correlated with wake after sleep onset (r = -0.34, p = 0.04).
Conclusions:
Sleep disturbance is associated with secondary peristaltic response to distension-induced esophageal stimulation in patients with GERD. Our study suggests that sleep disturbance per se may adversely influence the effectiveness of esophageal peristalsis and bolus clearance during sleep in patients with GERD.
Deglutition is a complex sensorimotor activity requiring coordination of multiple muscle groups, cranial nerves, and central systems, from the brainstem to the cortex, to achieve a timely, reliable swallow. Equally important is coordination with the respiratory system to ensure safety of the swallow. This fine balance is achieved with remarkable consistency and is due to elaborate neural networks, precise integration of aerodigestive tract reflexes, and patterned activity controlled by medullary centers. This chapter reviews the physiology of normal swallowing and its coordination with airway protection and the pathophysiology occurring when these processes fail.
The esophagus, which plays a primary role in food transport, is a collapsible organ with three main sections: upper esophageal sphincter (UES), esophageal body, and lower esophageal sphincter (LES). This chapter details basic pathophysiologic aspects of four disorders of esophageal motility, esophageal achalasia, esophageal spasm, nutcracker esophagus, and eosinophilic esophagitis and briefly describes nonspecific esophageal motility disorders. Each disorder causes different eating and digestive symptoms (dysphagia, abdominal and chest pain, heart burn, regurgitation of digested food) and may appear to mimic GERD or esophageal reflux. In some disorders, such as achalasia, much of the literature is based on the adult population, while pediatric information is noted only in case and retrospective studies. On the other hand, eosinophilic esophagitis is more prevalent in the pediatric population and may be related to food and environmental allergens. Diffuse esophageal spasm and nutcracker esophagus are benign and very rare in the pediatric population.
BACKGROUND Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism for AND AIMS: gastroesophageal reflux in the Western population. The major reflux mechanism in Chinese patients with GERD has not been studied before. METHODS: Fifty-four patients with GERD and 28 controls underwent stationary baseline manometry and the 24-h ambulatory esophageal pH monitoring. TLESRs were measured before and after an 850 kcal meal in the supine position. Primary peristalsis, secondary peristalsis, and esophageal acid clearance were measured by esophageal manometry. RESULTS: Total time esophageal pH less than or equal to 4 (7.3 vs 1.5, p = 0.001) was significantly higher in patients with GERD when compared to controls. Majority of acid reflux episodes was due to TLESR in both patients with GERD and controls. The frequency of TLESRs after meal was similar between patients with GERD and controls (1.0 vs 1.3/h, p = 0.34). There was no difference in the distribution of reflux mechanism between patients with GERD and controls. However, patients with GERD had a significantly lower successful primary peristalsis (59% vs 70%, p = 0.043) when compared to controls. CONCLUSION: The frequency of TLESRs was similar between patients with GERD and controls during stationary manometry. Primary peristalsis was impaired in Chinese patients with GERD. Esophageal motor dysfunction may contribute to the pathophysiology of GERD in the Chinese population.
Objectives:
Ineffective esophageal motility is frequently observed in gastroesophageal reflux disease (GERD) patients but its clinical relevance remains controversial. In healthy subjects and in patients with nonobstructive dysphagia, it has been demonstrated, by means of high-resolution manometry (HRM), that long breaks of esophageal peristalsis predict delayed bolus clearance.
Methods:
HRM and 24-h multichannel impedance-pH (MI-pH) monitoring were performed in 40 GERD patients with no evidence of hiatal hernia. Total bolus clearing time (BCT) in upright and supine position and acid exposure time (AET) were calculated.
Results:
Of the 40 patients, 23 showed a pathological AET and 15 erosive reflux disease (ERD). Patients with a pathological number of large breaks were characterized by a significantly lower BCT value in the supine position and higher AET. In all, 10/15 ERD patients (67%) and 5/25 nonerosive reflux disease patients (20%) were characterized by an abnormal number of small or large breaks (P<0.05). ERD patients were characterized by significantly higher AET and BCT in the supine position.
Conclusions:
GERD patients with a pathological number of large breaks, assessed by HRM, are characterized by a significantly prolonged reflux clearance in the supine position and higher AET. ERD patients display a higher number of esophageal breaks that might explain the development of erosions.
We aimed to investigate the hypothesis whether the presence of Ineffective esophageal motility would affect physiological characteristics of secondary peristalsis.
Secondary peristalsis was performed with slow and rapid air injections into mid-esophagus of 18 ineffective esophageal motility patients and 15 age matched controls. Severity of ineffective esophageal motility was defined by the application of combined multichannel intraluminal impedance and manometry.
Ineffective esophageal motility patients included eleven patients without impedance abnormality and seven patients with impedance abnormality during liquid and/or viscous swallowing. The prevalence of failed secondary peristaltic response during slow air injection was significantly greater in ineffective esophageal motility patients without impedance abnormality (3/11[27%], P < 0.001) and with impedance abnormality (4/7 [57%], P = 0.04) than healthy subjects. The threshold volume for inducing secondary peristalsis during rapid air injection was significantly greater in ineffective esophageal motility patients with impedance abnormality (6.1 ± 0.3 mL) than healthy subjects (4.6 ± 0.3 mL, P < 0.05) and ineffective esophageal motility patients without impedance abnormality (4.1 ± 0.4 mL, P < 0.05). The frequency of peristaltic response during rapid air injection was significantly lower in ineffective esophageal motility patients with impedance abnormality (40% [20-50%] than healthy subjects (90% [90-100%], P < 0.05).
Defective activation of secondary peristalsis is present in ineffective esophageal motility patients with impedance abnormality. Our study indicates that increased ineffective esophageal motility severity associated with defective triggering of secondary peristalsis may contribute to impaired esophageal clearance in patients with gastroesophageal reflux disease.
Esophageal adenocarcinoma is aetiologically associated with gastro-esophageal reflux, but the mechanisms responsible for the metaplasia-dysplasia sequence are unknown. Bile components are implicated. Impaired gallbladder function may contribute to duodenogastric reflux (DGR) and harmful GERD.
This study aims to compare gallbladder function in patients with Barrett's esophagus, adenocarcinoma, and controls.
Three groups of patients, all free of gallstone disease, were studied. Group 1: (n = 15) were normal controls. Group 2: (n = 15) were patients with >3-cm-long segment of Barrett's esophagus. Group 3: (n = 15) were patients with esophageal adenocarcinoma. Using real-time ultrasonography unit, gallbladder volume was measured in subjects following a 10-h fast. Ejection fraction was calculated before and after standard liquid meal and compared between the groups.
The mean percentage reduction in gallbladder volume was 50% at 40 min in the adenocarcinoma group compared with 72.4% in the control group (p < 0.001). At 60 min, gallbladder filling had recommenced in the control group to 64.1% of fasting volume while continuing to empty with further reduction to 63% in the Barrett's group and to 50.6% (p = 0.008) in the adenocarcinoma group. The mean gallbladder ejection fraction decreased progressively from controls to Barrett's to adenocarcinoma and was significantly lower in Barrett's group (60.9%; p = 0.019) and adenocarcinoma group (47.9%; p < 0.001) compared with normal controls (70.9%).
Gallbladder function is progressively impaired in Barrett's esophagus and adenocarcinoma. Gallbladder malfunction increases duodenogastric reflux, exposing the lower esophagus to an altered chemical milieu which, in turn, may have a role in promoting metaplasia-dysplasia-neoplasia sequence in the lower esophageal mucosa.
Achalasia is a motor disorder of the lower esophageal sphincter, which fails to relax on swallowing. Although a greater risk of esophageal squamous cell carcinoma among achalasia patients is fairly well established, no epidemiological study has evaluated the risk of esophageal adenocarcinoma in these patients.
We compiled a cohort of 2,896 patients recorded with a discharge diagnosis of achalasia between 1965 and 2003 in the Swedish Inpatient Register. The cohort was followed through 2003 via record linkages with essentially complete registers of cancer, causes of death, and migration. Standardized incidence ratios (SIRs) were used to estimate the relative risk of esophageal cancer in achalasia patients compared to the age-, sex-, and calendar period-matched Swedish population. We further estimated SIRs for esophageal cancer among patients treated with esophagomyotomy.
After excluding the first year of follow-up, we observed excess risks for both squamous cell carcinoma (SIR 11.0, 95% confidence interval [CI] 6.0-18.4) and adenocarcinoma (SIR 10.4, 95% CI 3.8-22.6) of the esophagus. Notwithstanding similar numbers of men and women in our achalasia cohort, 20 of 22 esophageal cancers developed in men (SIRs for adenocarcinoma and squamous cell carcinoma were 8.4 and 13.1, respectively). Increased SIRs among operated patients pertained mainly to esophageal squamous cell carcinoma. We found no evidence that surgical esophagomyotomy increases the risk of esophageal adenocarcinoma.
Male achalasia patients have substantially greater risks for both squamous cell carcinoma and adenocarcinoma of the esophagus. Small numbers preclude a firm conclusion about the risk among women.
The components of esophageal function important to success with laparoscopic adjustable gastric banding (LAGB) are not well understood. A pattern of delayed, however, successful bolus transit across the LAGB is observed.
Successful LAGB patients underwent a high-resolution video manometry study in which bolus clearance, flow, and intraluminal pressures were recorded. Liquid and semi-solid swallows and stress barium (a combination of semi-solid swallows and liquid barium) were performed. A new measurement, the lower esophageal contractile segment (LECS), was defined and evaluated.
Twenty patients participated (mean age 48.3 +/- 12.0 years, four men, %excess weight loss 65.6 +/- 18.0). During semi-solid swallows, two patterns of esophageal clearance were observed: firstly, a native pattern (n = 10) similar to that which is expected in non-LAGB patients; secondly, a lower esophageal sphincter-dependent pattern (n = 7), where flow only occurred when the intrabolus pressure increased during the lower esophageal sphincter (LES) aftercontraction. In both patterns, if there was incomplete bolus clearance, reflux was observed and was usually followed by another swallow. A mean of 4.5 +/- 2.9 contractions were required to clear the semi-solid bolus. Contractions with an intact LECS demonstrated longer flow duration: 7.1 +/- 3.8 vs.1.6 +/- 3.2 s, p < 0.005. During the stress barium, an intrabolus pressure of 44.5 +/- 16.0 mm Hg leads to cessation of intake.
In LAGB patients, normal esophageal peristaltic contractions transition to a LES aftercontraction, producing trans-LAGB flow. Repeated contractions are required to clear a semi-solid bolus. Incorporating measurements of the LECS into assessments of esophageal motility in LAGB patients may improve the usefulness of this investigation.
Previous studies have shown that non-erosive reflux disease (NERD) patients are less sensitive to proton pump inhibitor (PPI) treatment than patients with erosive reflux disease. The aim of this study was to investigate whether treatment with prokinetics in addition to omeprazole therapy would improve clinical symptoms, gastric emptying and esophageal peristalsis in PPI-resistant NERD patients with or without delayed gastric emptying.
Subjects were 64 consecutive patients presenting with typical symptoms of PPl-resistant NERD (n = 44) and 20 healthy volunteers. PPI-resistant NERD patients underwent mosapride citrate (15 mg/day) and omeprazole (20 mg/day) co-therapy for 12 weeks. We evaluated the clinical symptoms as well as gastric emptying and esophageal manometry before and after combined therapy. We measured both acylated- and des-acylated plasma ghrelin levels by the ELISA method. The primary endopoint was to investigate whether co-administration of mosapride citrate and omeprazole would improve clinical symptoms and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying.
T (max) value in PPI-resistant NERD patients was significantly higher than in healthy volunteers. Combination therapy with the prokinetic agent mosapride citrate and omeprazole significantly improved reflux symptoms and T (max) value in T (max) > 65 min NERD patients. Co-therapy also significantly reduced des-acylated-ghrelin levels in NERD patients with delayed gastric emptying.
Administration of mosapride citrate in addition to omeprazole improved gastro-esophageal reflux and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying.
(Uncorrected OCR) Abstract of thesis entitled Gastro-oesophageal reflux disease in Chinese Submitted by Wong Wai Man, Raymond for the degree of Doctor of Philosophy at The University of Hong Kong in 2004 The aims of this thesis were 1) to study the population and endoscopic prevalence of gastro-oesophageal reflux disease (GERD) and non-cardiac chest pain (NCCP); 2) to study the pathophysiology of GERD; 3) to evaluate upper gastrointestinal investigation of NCCP; 4) to validate a diagnostic GERD questionnaire; 5) to study the optimal dose of proton pump inhibitor (PPI) for the treatment of GERD in Chinese. A population-based telephone survey was performed to study the prevalence of GERD and NCCP, and the effect of anxiety and depressio n on health care utilisation in Chinese. The annual, monthly and weekly prevalence of GERD were 29.8%, 8.9% and 2.5% respectively. NCCP was present in 13.9% of subjects. GERD was associated with anxiety, depression, medical consultation, sick leave, and adverse effects on social life. The frequency of heartburn, the degree of depression, female gender and �eeling compromised social life�were independent factors associated with health care utilisation in GERD. Female gender, presence of GERD, and �eeling compromised social life�were independent factors associated with health care utilisation in NCCP. The endoscopic prevalence of oesophagitis, hiatus hernia, benign oesophageal stricture and Barrett� oesophagus were 3.8%, 1.7%, 0.08% and 0.06% respectively in a prospective study of 16,606 Chinese. Most patients were having a milder form of disease (LA grade A/B severity). Advanced age, use of nasogastric tube and gastrointestinal bleeding were associated with poor long-term outcome. i We then evaluated the usefulness of upper gastrointestinal investigation for NCCP in Chinese. Upper endoscopic pathology was present in 10% of patients. Typical acid reflux symptoms are uncommon in Chinese NCCP patients but abnormal oesophageal acid exposure was found in 29% of patients. Ineffective contractions were more frequently found in NCCP patients by 24-hour ambulatory manometry, which may have a bearing on the impaired quality of life in such patients. The major pathophysiological mechanism of GERD in Chinese has not been studied before. We demonstrated that the frequency of transient lower oesophageal sphincter relaxations (TLESRs) was similar between GERD patients and controls. TLESRs accounted for majority of acid reflux episodes in both GERD patients and controls. Primary peristalsis was significantly impaired in Chinese patients with GERD, suggesting oesophageal motor dysfunction may play a role in the pathophysiology of GERD in Chinese. There is no direct translation of the word �eartburn�in Chinese. No validated GERD symptom score exists in Chinese language. We have demonstrated that a 7- item GERD questionnaire has a sensitivity of 82% and a specificity of 84% for the diagnosis of GERD in Chinese. It could be used in epidemiological studies and interventional studies of GERD in Chinese. Proton pump inhibitor (PPI) is the most effective treatment for the initial and maintenance treatment of GERD. The optimal dosage of PPI for the treatment of GERD in Chinese remained to be defined. We have demonstrated that lansoprazole 30mg and lansoprazole 15mg once daily provide satisfactory reduction in oesophageal acid exposure, comparable improvement in symptoms profile and quality of life, and were equally effective in treating GERD in Chinese. ii
Barrett's esophagus has traditionally been regarded as the most severe end of the spectrum of gastroesophageal reflux disease and is of great clinical importance in view of the association with esophageal adenocarcinoma. Studies have documented high levels of esophageal acid exposure in Barrett's esophagus. Various pathogenetic mechanisms underlie this phenomenon. These include abnormalities in esophageal peristalsis, defective lower esophageal sphincter pressures, gastric dysmotility and bile reflux. Whilst these factors provide evidence for an acquired cause of Barrett's esophagus, an underlying genetic predisposition cannot be ruled out. Although the past decade has brought about many new discoveries in the pathogenesis of Barrett's esophagus, it has also added further controversy to this complex disorder. A detailed analysis of the gastrointestinal motor abnormalities occurring in Barrett's esophagus follows, with a review of the currently available literature and an update on this condition that continues to be of interest to the gastroenterologist.
Absztrakt
Azonos típusú betegségek esetén ugyanolyan műtéti eljárást alkalmazva, anatómiailag ideálisnak mondható per primam sebgyógyulást követően a késői funkcionális eredmények sokszor mégsem azonosak. Ennek hátterét kutatva 637 nyelőcső- és gyomorműtét összesített adatait és a műtétek alatt nyert szövetminták biokémiai, hisztológiai és elektronmikroszkópos feldolgozásával nyert eredményeit értékeltük. Az antirefluxműtétek utáni panaszok egyik lehetséges okaként a refluxos LES izomban hypertrophiára jellemző anyagcsere-változást és enteralis ganglionitist találtunk. A Z-vonal endoscopos klippelésével, majd ezt követően kontrasztanyagos nyelésröntgennel és substractiós képelemzéssel sikerült a rövid oesophagus jelenlétét preoperative igazolni. Megállapítottuk, hogy refluxbetegségben a nyitott műtétre az ezredforduló után is szükség lehet, elsősorban az anamnaesisben szereplő felhasi műtétek, sikertelen nyitott vagy laparoscopos rekonstrukciók, illetve szövődményes reflux eseteiben. A cardia adenocarcinomáiban a daganatot határoló ép szövet és a daganat proteolyticus enzimaktivitásainak – AMAN, CB és DPP I – hányadosa prognosztikus értékkel bír, segítségével a neoadjuváns kemo-radioterápia indikációja felállítható. Az “Akiyama-gyomorban” az operációt követően jelentkező panaszok jól korrelálnak a myoelektromos paraméterekkel és a gyomor contractilis aktivitásával. Az elektromechanikus adaptáció folyamata a műtét utáni tünetek fokozatos regressziójában nyilvánul meg. A gastro-jejuno-duodenalis interpositio (GJDI) egy olyan “second best” műtéti megoldás, mely mind a korai Barrett-carcinomák, mind a pepticus stricturák miatt végzett limitált oesophagus resectiókat követően a jejunalis vagy colon-interpositiók technikai nehézségei estén kerül előtérbe.
Unexplained chronic persistent cough has been shown to be associated with increased episodes of otherwise asymptomatic gastroesophageal reflux; however, normal subjects without cough also exhibit some reflux. We postulate that the prompt clearance of refluxed acid from the esophagus may play an important role in the prevention of cough, and we sought to determine if patients with chronic cough have impaired clearance. Thirty patients with unexplained chronic cough underwent 24-h ambulatory esophageal pH monitoring. Compared to 12 matched control subjects, patients experienced significantly more episodes (all values expressed as median [range]) of reflux per 24 h (88.3 [5.0 to 338.0] vs 5.7 [0 to 13.0]; p < 0.0001) and had impaired clearance of esophageal acid as measured by the duration of individual reflux episodes (3.0 [0.1 to 20.5] min per reflux vs 0.7 [0 to 2.5] min per reflux; p < 0.01). We conclude that patients with chronic persistent cough have impaired clearance of esophageal acid.
Gastroesophageal reflux (GER) has been implicated in otolaryngologic problems, particularly chronic hoarseness that cannot be attributed to other causes. To study this relationship, we used 24-h ambulatory intraesophageal or dual pharyngoesophageal pH monitoring in 33 patients with chronic hoarseness and laryngeal lesions suggestive of acid irritation. Twenty-six of the patients (78.8%) had pH evidence of severe GER, being at least three times greater than the upper limit of normal. In contrast to 19 patients with proven esophagitis, this GER was worse in the upright position. Of 15 patients with both pharyngeal and esophageal probes, three had esophagopharyngeal reflux, and two had atypical unexplained pharyngeal decreases in pH to below 4.0. Less than half of the 33 patients had the typical symptoms of GER, and standard esophageal tests usually yielded normal findings. Occult GER, predominantly in the upright position, appears to be common and severe in patients with chronic hoarseness, who have laryngeal lesions suggestive of GER. The causative mechanisms are not clear. The 24-h esophageal pH monitor is useful in screening this potentially treatable problem.
Contraction of the upper oesophageal sphincter combined with secondary peristalsis clears the oesophagus of refluxed gastric contents and protects the trachea, but the nature of these reflex stimuli remains controversial. Secondary peristaltic and sphincteric responses were measured during intraluminal infusion of 0.1 N hydrochloric acid and equiosmolar saline solutions in seven normal volunteers. Responses to a single volume infused at varying sites in the oesophagus and to progressively increasing volumes of test solution were measured. In addition oesophageal responses to similar degrees of distension induced by inflation of an intraluminal balloon were also recorded. The sphincteric responses to both stimuli were similar, decreasing in value with distance from the sphincter from values of 70 (68-85) mmHg (median (range] for HCl; and 70 (55-85) mmHg for NaCl at 5 cm below the sphincter to 40 (30-60) mmHg for both HCl and NaCl at 20 cm. As the volume of the solution infused into the proximal oesophagus was increased, the sphincter pressure also rose from a median basal value of 30 (25-50) mmHg to 40 (30-50) mmHg for HCl and NaCl after 1 ml, while after 7 ml infusion, the responses were greater, 65 (45-85) mmHg for HCl, and 60 (45-80) mmHg for NaCl. In the more distal oesophagus, responses were qualitatively similar but quantitatively smaller than proximally, being 30 (25-40) mmHg for HCl and 30 (25-50) mmHg for NaCl following 1 ml and 45 (40-55) mmHg for HCl and NaCl after 7 ml. Secondary peristalsis was also induced equally by both solutions and varied with volumes infused and site of infusion in a manner similar to the sphincter responses. After a 7 ml/min acid infusion 14 (1- 40) secondary contractions/three min were recorded at 5 cm and eight (2 - 18)/three min were recorded at 20 cm. Values for saline were similar, 13 (1- 38)/three min at 5 cm and eight (4 - 25)/three min at 20 cm. Oesophageal distension by a balloon positioned 10 cm below the sphincter induced identical clearance responses to those seen after similar volumes of either acid or saline infused at the same site. These results suggest that the principal stimulus for upper oesophageal clearance is intraluminal distension and do not support the idea that the oesophagus is pH sensitive.
We studied clearance of acid from the esophagus and esophageal emptying in normal subjects. A 15-ml bolus of 0.1 N hydrochloric acid (pH 1.2) radiolabeled with [99mTc]sulfur colloid was injected into the esophagus, and the subject swallowed every 30 seconds. Concurrent manometry and radionuclide imaging showed nearly complete emptying of acid from the esophagus by an immediate secondary peristaltic sequence, although esophageal pH did not rise until the first swallow 30 seconds later. Esophageal pH then returned to normal by a series of step increases, each associated with a swallow-induced peristaltic sequence. Saliva stimulation by an oral lozenge shortened the time required for acid clearance, whereas aspiration of saliva from the mouth abolished acid clearance. Saliva stimulation or aspiration did not affect the virtually complete emptying of acid volume by the initial peristaltic sequence. We conclude that esophageal acid clearance normally occurs as a two-step process: (1) Virtually all acid volume is emptied from the esophagus by one or two peristaltic sequences, leaving a minimal residual amount that sustains a low pH, and (2) residual acid is neutralized by swallowed saliva.
We investigated the mechanism of gastroesophageal reflux (GER) in 10 health volunteer subjects. Continuous recordings of intraluminal esophageal pH and pressure were obtained on two consecutive nights from 6:00 p.m. to 6:30 a.m. in each subject. During each study, the subject remained recumbent, except to eat a standardized meal after 1 h of basal recording. A manometric assembly with seven recording lumens monitored: (a) lower esophageal sphincter (LES) pressure via a sleeve device 6.5 cm in length, (b) esophageal-body motor activity, (c) swallowing activity in the pharynx, and (d) gastric pressure. An electrode 5 cm above the LES recorded esophageal pH. Sleep was monitored by electroencephalogram. All subjects showed wide variations of basal LES pressure. GER was not related to low steady-state basal LES pressure, but rather occurred during transient 5-30 s episodes of inappropriate complete LES relaxation. The inappropriate LES relaxations were usually either spontaneous or immediately followed appropriate sphincter relaxation induced by swallowing. The majority of GER episodes occurred within the first 3 h after eating. During the night LES relaxation and GER occurred only during transient arousals from sleep or when the subjects were fully awake, but not during stable sleep. After GER the esophagus was generally cleared of refluxed acid by primary peristalsis and less frequently by secondary peristalsis. Nonperistaltic contractions were less effective than peristalsis for clearing acid from the esophagus. We conclude that in asymptomatic recumbent subjects GER is related to transient inappropriate LES relaxations rather than to low steady-state basal LES pressure and also, that primary perstalsis is the major mechanism that clears the esophagus of refluxed material.
Secondary peristalsis contributes to oesophageal acid clearance. The aim of the study was to evaluate the integrity and characteristics of secondary peristalsis in patients with gastro-oesophageal reflux disease. Studies were performed in 22 patients with reflux disease and 20 age matched controls. Oesophageal motility was recorded at 3 cm intervals along the oesophageal body. Primary peristalsis was tested with 5 ml water swallows. Secondary peristalsis was stimulated with 10 ml boluses of air and water injected in the mid-oesophagus and by 5 second distensions with a 3 cm balloon at the same level. It was found that primary peristalsis was normal in 19 of 20 control subjects and in 14 of 22 patients with reflux disease. In patients with reflux disease, intact secondary peristalsis was triggered infrequently by air and water distension (median success rate of 0% for both stimuli) and occurred significantly less frequently than in control subjects (50% and 30% respectively). The frequency of balloon induced secondary peristalsis, however, was similar in the two groups (0% controls, 20% reflux disease). The major pattern of failure of secondary peristalsis was the complete absence of any oesophageal secondary peristaltic response. The amplitudes of the intact secondary peristaltic responses were not significantly different for the two groups. Peristaltic velocity for air and balloon induced secondary peristalsis was also similar in control subjects and patients with reflux disease whereas water induced secondary peristalsis was slower in the reflux patients. In conclusion, patients with reflux disease exhibit a pronounced defect in the triggering of secondary peristalsis.
This study examined the clearance of gastric acid from the oesophagus in ambulant patients with gastro-oesophageal reflux. Eighteen patients with proved reflux disease were studied, nine with (group 1) and nine without (group 2) endoscopic oesophagitis. Oesophageal pressure and pH were recorded over 24 hours. Pressures were measured by a probe with five sensors: a 5 cm long sensor in the lower oesophageal sphincter, three sensors in the body of the oesophagus, and one at the pharynx to detect swallowing. Oesophageal pH was monitored 5 cm above the lower oesophageal sphincter. Manometric activities were classified as either peristaltic or ineffective. The latter included simultaneous, non-transmitted, and low amplitude peristaltic contractions. A reflux episode was defined as starting when pH fell to less than 4 and ending when the pH rose to 5. When the rise to pH 5 took place in three or more discrete steps after motor responses to gastro-oesophageal reflux, the pH steps were labelled as initial change (I), middle changes (M), and last change (L). A total of 595 episodes of gastro-oesophageal reflux and 1626 associated motor events were analysed. Of these, 1331 (81.9%) were classed as primary peristaltic activity, 174 (10.7%) as primary ineffective activity, 46 (2.8%) as secondary peristaltic activity, and 75 (4.6%) as secondary ineffective activity. There were no significant differences in initial change (p > 0.05), middle changes (p > 0.05), and last change (p > 0.05) between group 1 and group 2. In all patients, the successive changes of pH in response to motor activity were significantly different (p = 0.0001) between initial, middle, and last changes. Last change was significantly higher when compared with initial (p=0.001) and middle changes (p<0.001). Primary oesophageal peristalsis was the most frequent motor response to gastro-oesophageal reflux. The last motor activity during reflux showed the greatest change in pH.
This study assessed the effect of prolonged intraluminal acidification on the motor activity of the entire oesophageal body (under controlled conditions). Intraoesophageal pressures were recorded in 13 endoscopy negative subjects with gastro-oesophageal reflux disease in whom saline, HC1 0.1 N, and saline solutions were infused (1.5 ml/min) blindly in the oesophageal body, 6 cm distal to the upper oesophageal sphincter for three consecutive periods of 45 minutes each. These findings were compared with those of a control group. Intraoesophageal acidification caused an increase in the deglutition frequency (p < 0.02), the occurrence of multipeaked waves (p < 0.04) as well as a decrease of the propagating velocity (p < 0.04) of the primary peristaltic contractions. Furthermore, intraoesophageal acidification determined an increase, at all levels of the oesophagus, of the duration (p < 0.04) and, more noticeable in the proximal oesophageal body, of the amplitude (p < 0.02) of primary peristaltic contraction waves. In conclusion prolonged intraoesophageal acidification can considerably affect frequency of deglutition, morphology, and propagating patterns of primary peristaltic contractions. This study shows that these effects are independent from volume distension of the oesophagus and supports the presence of acid sensitive receptors in the oesophageal mucosa.
Many years ago, it was proposed that the symptoms of heartburn correlated more closely with acid-induced esophageal motility abnormalities than with the presence of inflammation. This concept, however, has not been evaluated by modern manometric techniques. We monitored intraesophageal pressures during acid perfusion (0.1N hydrochloric acid) in 17 reflux patients with gross esophagitis and positive pain response and 17 age-matched controls. Using a low-compliance infusion system, amplitude, duration, velocity, and the presence of simultaneous and repetitive contractions in the body of the esophagus were evaluated. Amplitude did not change in either group. Duration did increase significantly during acid perfusion in reflux patients, but not in controls. Mean duration between groups, however, was similar before and during acid perfusion. No simultaneous contractions were observed, while three patients and two controls had repetitive contractions. A significant decrease in velocity was observed in both groups during acid perfusion. These studies indicate that acid-induced motor abnormalities are neither a common accompaniment nor necessary for the production of acid-induced pain in the esophagus.
(JAMA 1985;253:1914-1917)
THE ABILITY to empty refluxed gastric contents protects the esophagus from peptic digestion. Occasional gastroesophageal reflux probably occurs in everyone and has been demonstrated in 40% of asymptomatic, normal volunteers.1 There is evidence that patients symptomatic from reflux have disordered peristalsis resulting in inability to evacuate the esophagus.2-4 The duration of contact between refluxed material and esophageal mucosa would seem to influence the development and severity of esophagitis. A test was devised to determine whether or not the distal esophagus has a measurable ability to clear acid solution and whether or not this ability is altered in the presence of abnormalities.
Materials and Methods
A pH probe (Beckman) and three water-filled polyvinyl tubes (inside diameter, 0.034 inches) were passed through the nares and into the stomach without anesthesia in supine subjects. The tubes were joined so that the open tips were 5 cm apart and the pH probe
Background: The aim of the study was to investigate the dynamic characteristics of pathologic gastro-oesophageal reflux.
Methods: Five-channel ambulatory 24-h oesophageal pH monitoring was performed in 19 gastro-oesophageal reflux disease patients (age, 21-74 years) and in 19 healthy volunteers (age, 21-64 years). The pH was recorded at 3, 6, 9, 12, and 15 cm from the lower oesophageal sphincter (LOS), using a sample frequency of 4 Hz for each channel. Automated analysis included calculation of the ascending velocity of the refluxate and duration and extent (cm above the LOS) of all individual reflux episodes.
Results: In the patients more upright reflux episodes reached the proximal sensor than in the controls (20% and 11%, respectively, P < 0.01). The duration of the reflux episodes (measured at 3 cm above the LOS) was longer in the patients than in controls (P < 0.0001). This effect was independent of the proximal extent of the reflux episodes. Ascending velocities of upright acid reflux were higher in controls (1.8 to 2.7 cm/sec) than in patients (0.7 to 2.2 cm/sec; P = 0.01).
Conclusions: The dynamic characteristics of pathologic reflux differ significantly from those of physiologic reflux.
The aim of the present study was to investigate the effect of intraluminal pH on motor activity of the lower esophageal body. Liquid boluses of different pH values (7 to 2) were infused in the esophagus of 14 normal subjects during manometric recording of motor activity. Each test infusion elicited an esophageal motor response, either secondary peristalsis or simultaneous contractions. Secondary peristalsis was elicited by similar volumes of perfusates at pH 7, 6, 5, but significantly less volumes were needed with perfusates pH 4, 3, and 2. Simultaneous motor activity was not affected by intraesophageal pH value in the range investigated.
Conventional oesophageal manometric studies are open to criticism in that they take place on fasted immobile subjects in the artificial setting of a motility laboratory. A new 24-h pH and motility recording system combined with computerized data analysis was used to study patients with gastro-oesophageal reflux disease and oesophageal motor abnormalities under ambulant conditions. Acid reflux episodes were found to be precipitated by a variety of events with recognizable pressure patterns. Acid clearance abnormalities were demonstrated in patients with erosive oesophagitis but were confined to those with abnormal oesophageal motor function. Improved diagnostic accuracy was demonstrated in the recognition of oesophageal motor disorders.
Fiberoptic laryngoscopic examinations were performed on 40 patients with gastroesophageal reflux disease, 25 of whom had persistent laryngeal symptoms (dysphonia, cough, globus sensation, frequent throat clearing, or sore throat) and 15 without laryngeal symptoms who served as disease controls. Ten patients with laryngeal symptoms but none of the controls had laryngoscopic findings consistent with reflux laryngitis. Dual-site ambulatory pH recordings were obtained with the pH electrodes spaced 15 cm apart and with the proximal sensor positioned just distal to the upper esophageal sphincter. Patients in the three groups (disease controls: group 1; patients with symptoms but without laryngoscopic findings: group 2; and patients with both laryngeal symptoms and findings: group 3) were comparable in terms of age, smoking habit, the presence of esophagitis, and distal esophageal acid exposure. Proximal esophageal acid exposure was, however, significantly increased in groups 2 and 3, and nocturnal proximal esophageal acidification occurred in over half of these patients but in none of the group 1 patients. We conclude that the subset of reflux patients who experience laryngeal symptoms show significantly more proximal esophageal acid exposure (especially nocturnally) and often have laryngoscopic findings of posterior laryngitis not observed in control reflux patients.
Prolonged esophageal acid clearance, found in some patients with esophagitis, can be attributed in part to the peristaltic dysfunction observed in this population. In this study, we undertook to define the effect of commonly observed peristaltic dysfunction on volume clearance by obtaining concurrent videofluoroscopic and manometric recordings in patients with nonobstructive dysphagia or heartburn. Excellent correlation existed between the findings from the two studies. A single normal peristaltic wave resulted in 100% clearance of a barium bolus from the esophagus. At each recording site, luminal closure, as demonstrated by videofluoroscopy, coincided with the upstroke of the peristaltic pressure complex. Absent or incomplete peristaltic contractions invariably resulted in little or no volume clearance from the involved segment. Regional hypotensive peristalsis was associated with incomplete volume clearance by the mechanism of retrograde escape of barium through the region of hypotensive contraction. The regional peristaltic amplitude required to prevent retrograde escape of barium was greater in the distal compared with the proximal esophagus. The mean peristaltic amplitude associated with instances of retrograde escape was 25 mmHg in the distal esophagus compared with 12 mmHg in the proximal esophageal segments. Thus, the peristaltic dysfunction commonly seen in patients with esophagitis (failed and hypotensive peristalsis) likely leads to impaired volume clearance.
Esophageal exposure to acid is a major determinant in the pathogenesis of reflux esophagitis. In this study, we analyzed the esophageal peristaltic function of 177 patients and asymptomatic volunteers for abnormalities that could lead to prolonged esophageal acid clearance. The subjects were divided into five groups: normal volunteers, patient controls, patients with noninflammatory gastroesophageal reflux disease, patients with mild esophagitis, and ones with severe esophagitis. Manometric data were analyzed for the occurrence of failed primary peristalsis, for the occurrence of feeble peristalsis in the distal esophagus, and for hypotensive lower esophageal sphincter pressure. From an analysis of the data on control patients, peristaltic dysfunction was defined as the occurrence of either failed primary peristalsis or hypotensive peristalsis in the distal esophagus for over half of the test swallows. Peristaltic dysfunction was increasingly prevalent with increasing severity of peptic esophagitis, occurring in 25% of patients with mild esophagitis and 48% of patients with severe esophagitis. A correlation did not exist between the occurrence of peristaltic dysfunction and hypotensive lower esophageal sphincter pressure (less than or equal to 10 mmHg). We conclude that peristaltic dysfunction occurs in a substantial minority of patients with peptic esophagitis and could contribute to increased esophageal exposure to refluxed acid material.
To determine if hiatus hernia (HH) contributes to the delayed clearance of acid from the esophagus in patients with gastroesophageal reflux (GER), we performed simultaneous esophageal pH recordings and radionuclide studies in three study populations: 12 GER patients with HH, 5 GER patients with no HH, and 8 subjects with HH but no GER symptoms. Acid clearance was measured at 5 cm. above the manometrically located lower esophageal sphincter (LES) after injecting a 15-ml. bolus of 0.1 N HCl at 15 cm. above the LES. The acid was labeled with 200 mu Ci of 99mTc-sulfur colloid. Acid clearance was also measured at 10 cm. above the LES after injection of a 15-ml. bolus of 0.1 N HCl at 20 cm. above the LES. Acid clearance at 5 cm. above the LES was faster in GER patients with no HH compared to GER patients with HH and asymptomatic HH subjects. Acid clearance was faster at 10 cm. than 5 cm. above the LES in all HH and non-HH subjects studied. In non-HH subjects, each swallow resulted in an increase in pH (a monophasic pH response) at 5 and 10 cm. above the LES. In symptomatic as well as asymptomatic HH subjects, swallows resulted in an initial fall followed by a rise in pH at 5 cm. above the LES (a biphasic pH response). Radionuclide studies showed reflux of the isotope-labeled acid into the esophagus followed by clearance (a biphasic response) accompanying swallows in 15 of the 20 HH subjects. Swallow-induced reflux was not detected by radionuclide scanning in non-HH subjects. Based on these observations, we conclude that during acid clearance a small amount of acid is trapped in the HH sac and refluxes into the esophagus during subsequent swallows when there is relaxation of the LES, and these repeated episodes of acid reflux from the HH account for the delayed acid clearance observed in GER patients with HH.
The effect of intraluminal pH on motor activity of the lower oesophageal body was studied in patients with pathological gastro-oesophageal reflux. Liquid boluses with a pH range of 6.98-1.1, infused in the distal oesophagus of 21 patients during manometric recording of motor activity, elicited either secondary peristalsis or simultaneous contractions. Acid pH did not affect the threshold of distension required to elicit secondary peristalsis. Oesophageal responses to volumes of instillate did not differ in patients with normal and abnormal acid clearing test, nor in patients with a negative and positive acid perfusion test.
Many years ago, it was proposed that the symptoms of heartburn correlated more closely with acid-induced esophageal motility abnormalities than with the presence of inflammation. This concept, however, has not been evaluated by modern manometric techniques. We monitored intraesophageal pressures during acid perfusion (O.1N hydrochloric acid) in 17 reflux patients with gross esophagitis and positive pain response and 17 age-matched controls. Using a low-compliance infusion system, amplitude, duration, velocity, and the presence of simultaneous and repetitive contractions in the body of the esophagus were evaluated. Amplitude did not change in either group. Duration did increase significantly during acid perfusion in reflux patients, but not in controls. Mean duration between groups, however, was similar before and during acid perfusion. No simultaneous contractions were observed, while three patients and two controls had repetitive contractions. A significant decrease in velocity was observed in both groups during acid perfusion. These studies indicate that acid-induced motor abnormalities are neither a common accompaniment nor necessary for the production of acid-induced pain in the esophagus.
There is much evidence to suggest that peristaltic function is defective in esophagitis patients and that this defect may contribute to prolonged acid exposure, promoting esophageal mucosal injury. Abnormal peristalsis may also be related to the generation of reflux symptoms. We evaluated primary peristalsis and its relationship to symptoms under basal conditions and during saline and HCl perfusion in 15 symptomatic reflux patients with gross esophagitis and 15 healthy controls. In the basal state, LES pressure (15.3 vs 25.1 mm Hg) and peristaltic amplitude (74.2 vs 104.8 mm Hg) were significantly lower in subjects with gastroesophageal reflux disease (GERD) (P less than 0.05). During HCl perfusion, peristaltic amplitude and duration increased slightly, and peristaltic velocity slightly decreased similarly in both groups. There was no difference in the incidence of nonpropagated, segmental, or swallow-initiated simultaneous contractions, or change in resting intraesophageal pressure during HCl perfusion in control and GERD groups. This study identified abnormal contractile amplitude as a specific defect in the primary peristaltic wave of esophagitis patients but does not support a role for acid-induced motility changes in the generation of symptoms in GERD.
Oesophageal motility was studied in 59 patients before and again after prolonged acid perfusion. In group 1 (n = 16), who were asymptomatic during the acid perfusion, no significant motility differences were obtained by perfusion. In group 2 (n = 18), who had heartburn, and in group 3 (n = 25), who had angina-like chest pain during acid perfusion, significant (p less than 0.01-0.001) changes of motility were seen: these included higher peristaltic amplitude, longer contraction duration, and slower peristaltic velocity. In addition, patients in group 3 showed a decrease (p less than 0.01) of peristaltic propagation and had secondary wave activity more often (p less than 0.01) during acid perfusion. Significantly (p less than 0.01) more patients in group 3 showed secondary wave activity after acid perfusion than in group 2. Pretest motility investigation did not separate the two acid-sensitive groups from the acid-unsensitive one, whereas the investigation of the lower oesophageal sphincter (LOS) did. Thus, LOS incompetence was significantly (p less than 0.01) commoner in the two symptomatic groups than in the asymptomatic group. We suggest that the motility changes observed during acid perfusion are secondary to increased sensory stimulation from the oesophagus but are not the cause of the symptoms. However, nervous reflex reactions from other chest organs, such as the heart, may also explain the results.
p AIN in reflux esophagitis may be associated with alteration of both tile motility and acidity of tile esophagus, yet the causal relationship of these changes has not been established. Reflux esophagitis, like peptic ulcer, is usually an acid peptic lesion, x, 2 and pain in both conditions may conceivably be caused by the same factors, namely muscular spasm, contact of acid with the damaged mucosa, or a combination--i.e., acid-induced muscular spasm. Just as acid infusion 3 clarified the mechanism of peptic ulcer pain, so esophageal acid perfusion provides a means of studying pain in reflux esophagitis. It is now recognized that the pain of esophagitis can consistently be reproduced by this means 4 and the value of the test in the diagnosis of esophageal pain is established. 5-s But the mechanism by which acid provokes pain is a matter of controversy. Siegel and Hendrix 7 found that motility changes accompanied the pain, which they postulated arose from acid-induced muscle spasm; Tuttle et al., 9 however, coukl not demonstrate any constant motor changes and believed that these did not form an integral part of the pain mechanism. METHODS AND MATERIALS In order to study acid-induced pain, we measured esophageal intraluminal pressure and pH during diagnostic acid perfusion tests in 40 patients with reflux esophagitis, confirmed endoscopically in 34. A total of 29 patients had a demonstrable small hiatus hernia. In addition 14 healthy subjects were studied as controls. With the subject in the sitting position, a train of 3 open-ended tubes and a glass electrode were passed into the gullet until the pH electrode bulb lay 2-5 cm. above the estimated position of the cardia ventriculi, as assessed manometrically. Intraluminal pressure was recorded through two tubes whose openings were 10 cm. apart with that of the lower tube at the level of the pH electrode bulb. Solutions were infused through the third, which was placed so that the opening lay midway between the other two. During a control period normal saline was infused at a rate of 10 ml./min., and after 15 rain., without the patient's knowledge, 0.10 N HC1 was then infused at the same rate. Pain occurred during acid perfusion in 39 patients with esophagi,tis and in 8 controls. In 3 patients with esophagitis mild pain
Oesophageal acid clearing has been measured by counting the number of swallows needed to raise the lower oesophageal pH from 1.5 to 5.0 after instilling 15 ml 0.1 N hydrochloric acid. Normal subjects all had a result less than 12, as did asymptomatic patients with hiatal hernias. Patients with symptomatic gastrooesophageal reflux tended to have abnormal acid clearance, as did those with oesophageal motility disorders. Acid clearance correlated well with the mean duration of spontaneous episodes of acid reflux during 15-hour continuous recordings of lower oesophageal pH. Abnormal acid clearance was improved by raising the bedhead, by medical treatment for oesophagitis, and by metoclopramide. We conclude that abnormal acid clearing may result from disturbed oesophageal motility and render patients with these disorders susceptible to reflux oesophagitis. However, it also seems that gastrooesophageal reflux may lead to impaired acid clearance, both by creating abnormal motility and by effects on the oesophageal wall, and thus lead to a ;vicious-spiral' oesophagitis. In treating gastrooesophageal reflux, attention must be paid to improving acid clearance.
Recent studies have shown that impaired esophageal clearance of refluxed material during the sleeping interval plays a major role in the pathogenesis of esophagitis. The present investigation compares esophageal responses to both acid and water infusions during sleep in asymptomatic subjects. Fourteen healthy individuals were studied. The subjects were studied for two nights in the sleep laboratory. Each night involved four to six infusions of 15 ml of either sterile water or 0.1 N HCl. A similar infusion was conducted during the presleep waking interval. Acid clearance time was shown to decrease as a function of increasing wakefulness during the acid clearing interval. Arousal responses were significantly greater with acid infusions during sleep (p less than 0.05). Awakenings from sleep with acid infusions were associated with significantly greater swallowing rates than those associated with water infusions (p less than 0.01). Peristaltic parameters of amplitude, velocity, and duration were not differentially affected by acid versus water infusions or by sleep versus waking.
A variety of otolaryngological abnormalities have been attributed to the contact of gastroesophageal refluxate with respective structures of the aerodigestive tract. The aim of this study was to determine and compare the pharyngoesophageal distribution of gastric acid refluxate between patients with proven laryngitis attributed clinically to gastroesophageal reflux and three control groups.
An ambulatory 24-hour simultaneous three-site pharyngoesophageal pH monitoring technique was used to measure reflux parameters in the pharynx, proximal esophagus, and distal esophagus.
Between-group comparison showed no significant difference in the reflux parameters in the distal esophagus between the studied groups. A significantly higher percentage of distal reflux episodes reached the proximal esophagus in the laryngitis group than in the control groups (P < 0.01), and the number of pharyngeal reflux episodes and time of acid exposure were significantly higher in the laryngitis group than in the control groups (P < 0.001).
Compared with normal controls and patients with gastroesophageal reflux disease, pharyngeal reflux of gastric acid is significantly more prevalent and the ratio of proximal to distal esophageal acid reflux episodes is significantly increased in patients with posterior laryngitis. Simultaneous three-site ambulatory pharyngoesophageal pH monitoring may provide supporting evidence when the diagnosis of reflux-induced aerodigestive tract lesions is considered.
Previous studies of the mechanisms that precipitate acid reflux episodes have used short term hospital based measurements. A 24 hour pH and motility recording system, incorporating a sphincter monitoring device, has been developed to study naturally occurring acid reflux episodes in control subjects and patient groups with different grades of oesophagitis. Lower oesophageal sphincter relaxations related to episodes of acid reflux were common in control subjects (67% of episodes) but became more difficult to detect as the grade of oesophagitis increased (grade 0/1 - 67%, grade 2/3 - 35%, grade 4 - 13%). A variety of events that produced recognisable transdiaphragmatic pressure patterns were associated with acid reflux episodes. In control subjects 74% of acid reflux episodes were precipitated by belching but this mechanism became less evident as the grade of oesophagitis increased (grade 0/1 - 43%, grade 2/3 - 40%, grade 4 - 29%). Activities that produced a pressure gradient across the diaphragm became increasingly important as events precipitating acid reflux as oesophagitis became more severe (controls--2%, grade 0/1 - 15%, grade 2/3 - 11%, grade 4 - 22%). This study has shown the pressure events surrounding acid reflux in fully ambulant patients with gastro-oesophageal reflux disease.
Previous studies examining oesophageal acid clearance have employed a variety of techniques to induce or simulate acid reflux. Clearance abnormalities have been deduced from abnormal standard motility studies, barium radiology or from 24-h pH recordings. In this study a 24-h pH and oesophageal motility recording system was used to study naturally occurring acid reflux episodes in control subjects and in two groups of patients with severe acid reflux disease (erosive oesophagitis and oesophageal stricture). Acid clearance was compared between the subject groups. Patients with oesophageal stricture were found to have poor oesophageal peristaltic ability and particularly poor oesophageal acid clearance. Those with erosive oesophagitis had normal peristaltic swallowing but abnormal acid clearance. This study has characterized, for the first time, the abnormalities in acid clearance during naturally occurring acid reflux episodes in patients with severe reflux disease. A more complete understanding of these clearance abnormalities could influence future medical and surgical strategies in the management of severe gastro-oesophageal reflux disease.
Investigation of the motor events underlying gastroesophageal reflux has largely been confined to resting, recumbent subjects. The motor events associated with reflux during physical activity remain unknown. The aim of this study was to investigate the patterns of lower esophageal sphincter (LES) function underlying reflux in healthy subjects and the effect of exercise and physical activity on reflux mechanisms.
LES pressure was recorded with a perfused sleeve sensor in 10 healthy subjects; intraluminal transducers recorded pressure in the stomach, esophagus, and pharynx, and pH was recorded 5 cm above the LES. Signals were stored in a portable data-logger. Recordings were made for 24 hours, including moderate physical activity, periods of rest and sleep, standardized meals, and standardized exercise.
Most reflux episodes (81 of 123; 66%) occurred in the 3 hours after food intake; only 2 episodes occurred during exercise. LES pressure was < or = 3 cm H2O in 79% of reflux episodes. Transient LES relaxation was the mechanism of reflux in 82% of episodes, irrespective of activity or body position, whereas swallow-related LES relaxations accounted for 13% and persistently absent LES pressure accounted for 1%. Straining occurred in only 20% of episodes.
In ambulant healthy subjects, accurate continuous recording of LES function is possible, reflux usually occurs during transient LES relaxations, and straining is not a major factor in the induction of reflux.
Conventional perfused manometry has led to extensive study of phasic contractile activity in the human esophagus, but little is known about esophageal tonic activity. The aims of this study were to assess esophageal smooth and striated muscle tone and the effect of a smooth muscle relaxant (amyl nitrite, 0.3 mL inhalation) on this tone.
Using a computerized isobaric recording system (barostat), esophageal tonic activity in 13 healthy subjects was recorded. Two parameters were analyzed: compliance and resistance to initial stretch (resting tone).
The smooth muscle esophagus was significantly more compliant but presented a greater resistance to initial stretch than the striated muscle section. Amyl nitrite affected only the smooth muscle section, significantly increasing compliance and decreasing the resistance to initial stretch. Significant chest pain and/or discomfort occurred only during striated muscle esophagus distension (10 of the 13 subjects at 25 mm Hg distending pressure).
Active tone is present in the smooth muscle esophagus and can be modulated by a smooth muscle relaxant. Compliance and resting tone differ between the smooth and striated muscle segments of the esophagus. Assessment of tone in patients with esophageal motor disorders and noncardiac chest pain should provide further insights into these disorders.
This study examined the hypothesis that impaired oesophageal peristalsis was associated with delayed oesophageal clearance of acid in patients with progressive systemic sclerosis (PSS), some of whom are thought to have impaired oesophageal sensitivity to acid. Sixteen patients with PSS had: (a) oesophageal manometry and endoscopy; (b) acid perfusion of the oesophagus with simultaneous measurement of intraoesophageal pH during perfusion and for the next 10 minutes; (c) 22 hour monitoring of intraoesophageal pH; and (d) an evaluation of reflux symptoms during and after perfusion and during overnight pH monitoring. By oesophageal manometry, eight patients had normal peristalsis and eight patients had impaired peristalsis. Oesophageal endoscopy was unremarkable in patients with normal peristalsis, whereas all patients with impaired peristalsis had oesophagitis. The time needed to clear the oesophagus of perfused acid was shorter (p < 0.01) in patients with normal peristalsis and acid clearance time was significantly correlated (p < 0.01) with acid exposure time during overnight pH monitoring. During and after oesophageal perfusion, the nature, duration, and severity of symptoms did not differ between the groups, but overnight symptoms lasted longer (p < 0.05) in patients with impaired peristalsis. It is concluded that in PSS: (1) Impaired oesophageal motility delayed the clearance of acid and increased the exposure time to acid. (2) Acid clearance time is a useful parameter of impaired oesophageal motor function. The assessment of acid clearance time can be used as an alternative to overnight pH monitoring, to assess the impairment of oesophageal acid clearance. (3) Oesophageal sensitivity to acid was preserved in patients with impaired peristalsis and oesophagitis. (4) Reflux symptoms lasted longer in patients with prolonged oesophageal acid exposure but were still reported for a small fraction of the total acid exposure time. Thus, reflux symptoms reflect poorly prolonged exposure of the oesophagus to acid and are not a reliable guide to acid injury of the oesophagus in PSS.
Whether the oesophageal motor response to reflux, as recorded over 24 hours, is impaired in patients with reflux oesophagitis was investigated. Twenty three patients with oesophagitis (Savary-Miller grades I-IV) and 23 control subjects matched for age and sex underwent 24 hour ambulatory pH and pressure monitoring. All contractions occurring in the 2 minute period after the onset of each reflux episode were analysed automatically using dedicated computer algorithms. A total of 2085 reflux episodes occurred--1513 in patients and 572 in controls. Oesophageal acid exposure was greater (p < 0.01) in patients than in controls (mean (SEM) % time pH < 4 13.3 (1.7) and 5.3 (0.9)%, respectively). The mean duration of the supine reflux episodes was longer (p < 0.01) in patients (11.2 (2.8) minutes) than in controls (5.1 (1.8) minutes). In the upright period, no significant differences in the motor response to reflux were found. In the supine period, the patients showed a higher number of reflux induced contractions (4.40 (0.61) v 1.62 (0.31), p < 0.01), a higher contraction amplitude (4.55 (0.42) v 2.99 (0.71) kPa, p < 0.02) and longer contractions (1.86 (0.19) v 1.32 (0.29) seconds, p < 0.05). The percentages of peristaltic and simultaneous contractions that occurred in response to supine reflux did not differ between the two groups. In patients with reflux oesophagitis the motor response of the oesophagus to reflux is not impaired. During the supine period the response is even stronger than in healthy controls.
Gastroesophageal reflux frequently occurs during spontaneous transient lower esophageal sphincter relaxations (TLESRs). The aim of this study was to determine the motor activity in the body of the esophagus during TLESRs in 10 healthy subjects.
Esophageal contractions were recorded 13,8,and 3 cm above a sleeve that measured LES pressure. A balloon was inflated 8 cm above the sleeve to induce an esophageal tonic contraction (artificial high-pressure zone).
No relaxation of the artificial high-pressure zone was detected at the onset or during spontaneous TLESRs before gastroesophageal reflux. Esophageal acidification provoked no changes or increased the pressure in the artificial high-pressure zone by 47.9% +/- 12% When gastroesophageal reflux abruptly distended the esophagus (common cavity), a relaxation of the artificial high-pressure zone of 51.1% +/- 6.6% was observed in 78% of the instances. Deglutitive or secondary contractions during spontaneous TLESRs traveled down the esophagus in 96.5% of the instances.
Stimuli that induced spontaneous TLESRs did not by themselves inhibit muscle contractility in the body of the esophagus. Acidification without distention of the lower esophagus frequently increased esophageal tonic contractility. Abrupt lower esophageal distention by reflux of air or acid partially relaxed the artificial high-pressure zone in the esophageal body, probably to assist gastric venting.
To determine (1) the appropriate omeprazole (Prilosec) dose required for adequate acid suppression in asthmatics with gastroesophageal reflux, (2) whether aggressive acid suppressive therapy of gastroesophageal reflux improves asthma outcome in asthmatics with gastroesophageal reflux, (3) the time course of asthma improvement, and (4) demographic, esophageal, or pulmonary predictors of a positive asthma response to antireflux therapy.
Thirty nonsmoking adult asthmatics with gastroesophageal reflux (asthma defined by American Thoracic Society criteria and reflux defined by symptoms and abnormal 24-hour esophageal pH testing) were recruited from the outpatient clinics of a 900-bed university hospital. Patients underwent baseline studies including a demographic questionnaire, esophageal manometry, dual-probe 24-hour esophageal pH test, barium esophogram, and pulmonary spirometry. During the 4-week pretherapy phase, patients recorded reflux and asthma symptom scores and peak expiratory flow rates (PEFs) upon awakening, 1 hour after dinner, and at bedtime. Patients began 20 mg/d omeprazole, and the dose was titrated until acid suppression was documented by 24-hour pH test. Patients remained on this acid suppressive dose for 3 months. Responders were identified by a priori definitions: asthma symptom reduction by >20% and/or PEF increase by >20%. Asthma symptom scores, PEF's baseline and posttherapy pulmonary spirometry were analyzed.
Twenty-two (73%) patients were asthma symptom and /or PEF responders: 20 (67%) were asthma symptom responders, and 6 (20%) were PEF responders. Responders reduced their asthma symptoms by 57% (P<0.001), improved their morning and night PEFs by 8% and 9% (both P <0.005), and had improvement in forced expiratory volume at 1 second (P <0.02), mean forced expiratory flow during the middle half (25% to 75%) of the forced vital capacity (P <0.04), and peak expiratory flow (P <0.01) with acid suppressive therapy. Mean acid suppressive dose of omeprazole was 27 mg/d (+/-2.2) with 27% (8) patients requiring more than 20 mg/d. The presence of regurgitation or excessive proximal esophageal reflux predicted asthma response with 100% sensitivity, 100% negative predictive value, specificity of 44% and a positive predictive value of 79%.
Acid suppressive therapy with omeprazole improves asthma symptoms and/or PEFs by >20% and improves pulmonary function in 73% of asthmatics with gastroesophageal reflux after 3 months of acid suppressive therapy. Many asthmatics (27%) required >20 mg/d of omeprazole to suppress acid. The presence of regurgitation and/or excessive proximal esophageal reflux predicts a positive asthma outcome.
We investigated the mechanisms of slow fluid infusion-induced secondary peristalsis and the effects of hydrochloric acid on this response. In 13 chronically esophagostomized opossum, acidic and neutral barium sulfate were infused into the distal esophagus at a rate of 1.1 ml/min, while recording the esophageal dimension by videofluoroscopy and esophageal intraluminal pressure concurrently. The effects of atropine, tetrodotoxin, capsaicin, and bilateral cervical vagotomy on the response to slow fluid infusion were examined. Acidic barium initiated secondary peristalsis more frequently and at shorter latency with less increase of preperistaltic intraesophageal pressure than neutral barium (P < 0.05). Atropine abolished secondary peristalsis initiated by neutral barium. For acidic barium, atropine decreased the incidence of secondary peristalsis, increased the latency for initiation of secondary peristalsis, and initiated secondary peristalsis more distally (P < 0.05). Tetrodotoxin or vagotomy and capsaicin abolished activation of secondary peristalsis. We concluded that secondary peristalsis can be stimulated in response to slow distension by minute amounts of fluid. This peristalsis is atropine and capsaicin sensitive and vagally mediated. The presence of acid significantly lowers the threshold for stimulation of secondary peristalsis induced by slow fluid distension. This effect seems to be atropine resistant.
Abstract Information on the mechanism of gastro-oesophageal reflux in patients with reflux disease is limited largely to studies in resting recumbent subjects. Evidence exists that both posture and physical activity may influence reflux. The aim of this study was to investigate reflux mechanisms in ambulant patients with reflux oesophagitis.
Concurrent ambulatory oesophageal manometry and pH monitoring were performed in 11 ambulant patients with erosive oesophagitis. Lower oesophageal sphincter (LOS) pressure was monitored with a perfused sleeve sensor. Recordings were made for 90 min before and 180 min after a meal. At set times patients sat in a chair or walked.
LOS pressure was ≤2 mmHg at the time of reflux for 98% of reflux episodes. Transient LOS relaxation was the most common pattern overall and the predominant pattern in seven patients, whilst persistently absent basal LOS pressure was the most common pattern in four patients. The pattern of LOS pressure was not altered by the presence of hiatus hernia or by walking. Straining occurred at the onset of 31% of acid reflux episodes but often followed the development of an oesophageal common cavity. The occurrence of straining was not influenced by walking.
In ambulant patients with reflux oesophagitis: (1) LOS pressure is almost always absent at the time of reflux, usually because of transient LOS relaxation, (2) persistently absent basal LOS pressure is an important mechanism of reflux in a few patients, (3) straining may help to induce acid reflux in a variable proportion of occasions and may in some instances be a response to gas reflux, and (4) walking does not influence the occurrence of reflux or its mechanisms.
To compare oesophageal motor responses to gastro-oesophageal reflux (GOR) in 16 healthy controls (group 1) and 25 reflux patients, 15 without (group 2) and 10 with (group 3) oesophagitis.
All subjects underwent 24 hour ambulatory oesophageal pH measurements (5 cm above the lower oesophageal sphincter (LOS)) combined with pressure monitoring (5, 10, and 15 cm above the LOS for oesophageal body motility and 27 cm above the LOS for voluntary swallow detection). Contraction patterns (peristaltic, simultaneous, isolated, mixed type, and non-transmitted swallows) and peristaltic contraction wave characteristics (amplitude, duration, and velocity) during GOR were compared in the three groups.
The average number of motor activities per minute was significantly higher in group 1 (p < 0.05). In all groups, the most common motor contraction pattern was peristaltic. The percentage of peristaltic activity per subject was significantly higher in group 1 (p < 0.05). There were no significant differences in other contraction patterns among the three groups (p > 0.05). Of the peristaltic contraction wave characteristics there were no significant differences in any parameters (amplitude, duration, and velocity) among the three groups (p > 0.05). The average pH increment in response to motor activities was significantly higher in group 1 (p < 0.05).
Motor responses to GOR were found to be predominantly primary peristaltic in all groups. During GOR, reflux patients have less frequent activity, a smaller proportion of activity is peristaltic, and the average pH increment in response to motor activities is reduced compared with controls.
Permissive role of the esophageal body during transient LES relaxations (TLESRs). A mechanism for increased reflux in patients with reflux esophagitis
- D Sifrim
- G Vantrappen
- Janssen
Sifrim D, Vantrappen G, Janssen J. Permissive role of the esophageal body during transient LES relaxations (TLESRs). A mechanism for increased reflux in patients with reflux esophagitis. Neurogastroenterol Motil. 1994;6:171. Abstract.