Duodenal Acid Clearance
Digestive Diseases and Sciences,Vol.50,No.8(August2005),pp.1553–1560(C 2005)
DOI:10.1007/s10620-005-2880-6
Duodenal Acid Clearance in Humans:
Observations Made with Intraluminal
Impedance Recording
GUILLAUME SA VOYE,MD,JAC OORS,RN,and ANDR′E SMOUT,MD,PhD Duodenal acid clearance appears to be involved not only in the pathogenesis of duodenal ulcer disease but also in functional dyspepsia.Duodenal contractile activity can help to maintain neutral pH in the duodenum by mixing acid with bicarbonate or by aborally transporting the acid load.Intraluminal impedance recording,allowing the detection of nonacid liquid boluses,can be carried out concomi-tantly with antroduodenal manometry and pH recording and may thus provide useful information about the mechanisms involved in duodenal clearance of endogenous acid and volume boluses.Eight
H.pylori-negative healthy volunteers were studied with two catheters positioned across the pylorus,
allowing the recording of?ve impedance signals(one antral,one pyloric,and three duodenal)si-multaneously with six pressure signals(two antral,one pyloric,and three duodenal)as well as distal antral and proximal duodenal pH.During phase II of the migrating motor complex,which is known to be associated with the highest duodenal acid exposure,each duodenal acidi?cation event(de?ned as
a pH drop>2pH units)was characterized by its maximal amplitude,duration,temporal relationship
with antroduodenal manometric events,and relation to impedance variations.Acid was considered to have been cleared from the duodenum when the preacidi?cation pH was restored(±0.2unit).A total of164duodenal pH drops were recorded during the323min of phase II recordings.Eleven percent of the duodenal acidi?cation events were short-lived(<10sec).All of these events were temporally associated with a propagated antroduodenal contraction and a short-lived drop in impedance,sug-gesting rapid aboral passage of the acid bolus.The long-lived duodenal acidi?cation events lasted a mean of32sec(range,25–66sec).In90%of these events an antroduodenal propagated contraction was recorded at the time of onset.Repetitive duodenal contractions followed the onset of the long-lived acidi?cation events in34%of the cases.These remained present until complete clearance of the acid.In81%of the long-lived acidi?cation events,recovery of the associated impedance drop occurred simultaneously with the pH recovery,suggesting a complete clearance of the bolus.Less frequently(19%),the duodenal pH recovered while the impedance remained low,suggesting that the bolus was not cleared but neutralized.Interdigestive duodenal acidi?cation events usually last about 30sec.They evoke duodenal contractions in only one-third of https://www.wendangku.net/doc/1f9656612.html,bined pH and impedance recording makes it possible to distinguish between neutralization of acid boluses and their complete total clearance.
KEY WORDS:duodenal acid clearance;transpyloric?uid transport;multichannel impedance measurement;antroduodenal motility.
Manuscript received October13,2004;accepted December13,2004. From the Gastrointestinal Research Unit,University Medical Center, Utrecht,The Netherlands.
Address for reprint requests:Dr.A.J.P.M.Smout,Gastrointestinal Motility Unit,University Medical Center,Box85500,3508GA Utrecht, The Netherlands;a.smout@azu.nl.Responses to duodenal acid exposure represent a key fac-tor in the regulation of upper gastrointestinal physiology. The presence of acid in the duodenum is a signal for con-trol mechanisms leading to inhibition of gastric acid pro-duction and to stimulation of pancreaticobiliary secretion
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SA VOYE ET AL.
and mucosal bicarbonate secretion (1,5,9,18,28).It also affects gastric emptying,contributes to relaxation of the proximal stomach,and modulates interdigestive gas-tric motility (20,31,53).Moreover,in the fasting con-dition proximal duodenal acidity varies with the phases of the interdigestive motor complex (52).Our knowledge of the ways in which the duodenum disposes of the acid load coming from the stomach is mainly based on obser-vations made following the administration of exogenous acid.Duodenal acid clearance is thought to be largely controlled by duodenal acid-induced motility that helps to maintain neutral pH in the duodenum by mixing acid with bicarbonate and by aborally transporting the acid load.Duodenal acid clearance is involved not only in the pathogenesis of acid-dependent disease like duodenal ul-cer (2,10,27)but also in functional dyspepsia,where an abnormal duodenal clearance of exogenous acid has been observed (39).Moreover,dyspeptic patients may bene?t from drugs that inhibit acid secretion (15,34).Excessive exposure of the duodenum to gastric acid and alteration of its clearance might be important factors in the origin of gastrointestinal symptoms per se.Recent reports also sug-gest that duodenal acidi?cation increases the sensitivity to gastric distension and inhibits gastric accommodation to a meal (30)in healthy subjects,suggesting a link between alteration of proximal gastric function observed in dys-peptic patients (50)and duodenal acid clearance.
Multichannel intraluminal impedance measurement was recently developed for studies on esophageal tran-sit and gastroesophageal re?ux (11,12,43–47,49,51).This technique has made it possible to assess ?uid trans-port in other parts of the human upper gut as well.Recent studies in healthy subjects using impedance monitoring and concomitant manometry have shown that ?uid pres-ence in the duodenum and transport through the pylorus can be observed in all phases of the antral or duodenal
mi-
Fig 1.Schematic representation of the two catheters used in this study.The pH catheter had two pH electrodes,5cm apart.The pressure and impedance monitoring catheter had six metallic rings at 2-cm intervals and six perfused sideholes.
grating motor complex (35,36,40,41).When carried out concomitantly with pH recording,intraluminal impedance monitoring may provide important information on duo-denal endogenous acid clearance,distinguishing between acid and nonacid liquid.
The aim of the present study was to describe,in healthy volunteers,the use of intraluminal impedance monitoring for the assessment of mechanisms involved in interdiges-tive duodenal acid clearance.
MATERIALS AND METHODS
Subjects
Eight healthy volunteers (?ve female,three male;mean age,24±4years;body mass index,21.8±4.1kg/m 2)were studied after written informed consent.Subjects did not suffer from any gastrointestinal complaints,did not undergo major surgery in the past,did not suffer from any chronic disease,and did not use medication known to affect gastrointestinal motility.The study protocol was approved by the Human Research Committee of the Utrecht University Medical Center.
Methods
Combined Impedance,Double pH,and Manometric Recordings.The technology used in these studies involved combined monitoring of intraluminal impedance,intraluminal pressure,antral and duodenal pH,and transmucosal gastroduo-denal potential difference.Two catheters were used.One of these was a water-perfused catheter that incorporated six sideholes at 2-cm intervals (two in the antrum,one in the pylorus,and three in the duodenum)and six circular electrodes (two in antrum,four in duodenum)positioned between the sideholes,yielding six pres-sure and ?ve impedance signals.The other was a single-use,2.1-mm-diameter double antimony pH catheter (Sandhill,Inc.,Highlands Ranch,CO)tied alongside the ?rst one with adhesive strips.This catheter allowed the recording of two pH signals,5cm apart,one in the antrum (0.5cm proximal to A2)and one in the proximal duodenum (0.5cm distal to D1)(Figure 1).During the study,the position of the catheters was monitored continu-ously by measurement of the transmucosal potential difference
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Digestive Diseases and Sciences,Vol.50,No.8(August 2005)
DUODENAL ACID CLEARANCE IN HUMANS
(TMPD)between the distal antral sidehole A2and the most proximal duodenal side hole D1.The two TMPD channels were perfused with degassed saline from separate reservoirs,at a rate of0.2ml/min.A disposable Ag/AgCl electrode,attached to the forearm,was used as the reference electrode for TMPD mea-surment.The other manometric channels were perfused with distilled water at a rate of0.8ml/min.The pressures from the six perfused sideholes,the pH signals from the two pH sensors,and the?ve impedance signals were recorded using a dedicated sta-tionary system(InSIGHT Stationary MII system,Sandhill Scien-ti?c Inc.,Denver,CO,USA).For measurement of the impedance signals a2-kHz current was used,which was passively limited to less than8μA.All signals were sampled at a rate of10Hz and stored on the hard disk of a computer for subsequent analysis. The persistence of the correct attachment of the catheters was checked at the end of each recording session.
Study Protocol.After an overnight fast the catheters were in-troduced transnasally and positioned across he pylorus.The sub-jects were studied in a supine position allowing15?inclination. After positioning of the catheter using TMPD measurement(and ?uoroscopy if necessary),an accommodation period of30min followed.Thereafter,interdigestive recording took place until a complete cycle of the interdigestive migrating motor complex (MMC)had been observed.
Data Evaluation
Analysis of the combined impedance,manometric,and dou-ble pH recordings was conducted following successive steps.
Visual Analysis of Manometric Recordings.This analysis was done only when the antral TMPD was?15mV,and the difference between the two was at least15mV,indicating correct position(13). Visual analysis was used to identify the MMC phases.Phases III were detected in the antrum and duodenum.Antral phase III was de?ned as a burst of regular contractions lasting more than1min with a contraction frequency of2.5–3.5min?1,with a temporal overlap with duodenal phase III.Duodenal phase III activity was de?ned as regular contractions at a frequency of10–12min?1 during at least1min occurring in all duodenal recording sites, antegradely propagated,and followed by at least5min of relative quiescence(phase I).Phase II consisted of pressure waves>1. 4kPa occurring at a rate higher than2per10min and less than the maximum frequency of the antrum(3contractions/min)or the duodenum(10–12contractions/min).
Analysis of pH Recordings.Mean antral and duodenal pH were calculated during each each of these events,and it was determined whether or not the threshold of pH4was passed. The pre-event pH was calculated as the mean pH observed in the 10-sec period before the onset of the pH drop and the acidi?cation event was regarded as cleared when the pH recovered its pre-event value±0.2pH unit.
Characterization of Transpyloric Bolus Assessed by Impedance Recordings.As described previously,liquid bo-lus transport across the pylorus was detected as a drop in impeda antral and one duodenal channel,implying presence in a4-cm-long stretch,or as a propagated impedance drop ob-served in at least three recording channels including one antral and one duodenal channel(41).Impedance baseline was deter-mined in the5-sec period immediately preceding the onset of the impedance drop.Following bolus transport across the py-lorus a bolus was considered to be present in the duodenum as long as the impedance remained low.The bolus was considered to be cleared from the duodenum when duodenal impedance had recovered to its pre-event value as described by Nguyen et al.(36).
Temporal Relationship Analysis Among Duodenal pH Drops,Impedance Changes,and Pressure Events.A duo-denal pH drop was considered to be associated with a propa-gated antroduodenal contraction if such a manometric event was recorded within10seco of the onset of the pH drop.A?uid trans-port event was considered to be concomitant with a contraction or a pH drop if present within a10-sec interval.
Statistical Analysis.When quantitative data were not nor-mally distributed,comparisons of characteristics in impedance events between interdigestive phases were performed using the unpaired Mann–Whitney U test.For qualitative data the chi-square test with Yates correction was used.Data from pH, manometry,and impedance measurements are expressed as means±SE,unless stated otherwise.
RESULTS
During the eight recording sessions the catheter was in a correct transpyloric position during82±12%of the time. In total,41min of antral phase III,88min of antral phase I, and323min of antral phase II were recorded.Mean phase durations were14±7min for phase I,54±41min for phase II,and5.9±4.2min for phase III.
Mean antral and duodenal pH values during each phase of the MMC are summarized in Table1.Transpyloric?uid transports occurred in all three phases of the MMC.The total number of transport events was higher in phase II (20±8.4)than in phase I(2.3±1.9)and phase III(4.8±3.0;P<0.05).Only10transpyloric?uid transports were recorded without an associated duodenal pH drop,4in phase I and6in phase II(Figure2).
In the duodenum,a total of164acidi?cation events were observed during phase II of the MMC,89%of these reach-ing the threshold of pH<4.These acidi?cation events comprised35±18%of the time in phase II.
Based on their duration two clearly distinct patterns of acidi?cation events were observed.Eleven percent of the duodenal acidi?cation events were“short-lived”;all lasted<10sec(Figure3).These pH events were always temporally associated with a propagated antroduodenal T ABLE1.M EAN A NTRAL AND D UODENAL pH V ALUES D URING ALL
P HASES OF THE MMC
Phase I Phase II Phase III Antral pH4.6±2.32.1±1.3*3.5±3.2 Duodenal pH6.7±1.25.2±3.5*6.5±1.6 Number of transpyloric2.3±1.9?20±8.4*4.8±3
?uid transport events
*P<0.005,Phase II versus Phase I and Phase III.
?P<0.05,Phase I versus Phase III.
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SA VOYE ET
AL.
Fig 2.Example of transpyloric ?uid transport without concomitant duodenal pH drop.P,pressure;Z,impedance.
contraction and a short-lived drop in impedance,suggest-ing rapid aboral passage of an acid bolus.
All other acidi?cation events were “long-lived”events,lasting a mean of 32sec (range,25–66sec).An
antro-Fig 3.Example of a short-lived duodenal acidi?cation event temporally associated with a propagated antroduodenal contraction and a short-lived drop in impedance.P,pressure;Z,impedance.
duodenal propagated contraction was recorded at the time of the onset of these events in 90%.Contractile duodenal activity was recorded following the onset of the acidi?ca-tion event in 34%of the cases,which activity remained
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HUMANS
Fig 4.Example of contractile duodenal activity following an impedance drop and a long-lived duodenal acidi?cation event,which remains present in the duodenum until complete clearance of the acid.P,pressure;Z,impedance.
present in the duodenum until complete clearance of the acid (Figure 4).In 81%of these long-lived acidi?cation events the impedance recovered to its pre-event value si-multaneously with the pH recovery,suggesting complete clearance of the bolus.Less frequently (19%),the duode-nal pH recovered while the impedance remained low,sug-gesting that the bolus remained present but with a higher pH (Figure 5).No concomitant duodenal motor
activity
Fig 5.Example of duodenal pH recovery with a persistent impedance decrease with associated contractile duodenal activity.P,pressure;Z,impedance.
was observed during all but one of these complete clear-ance events.
DISCUSSION
The novel observation made in the present study is that in healthy human subjects,two mechanisms of duo-denal acid clearance in the interdigestive state can be
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distinguished:complete total clearance and,less fre-quently,persistence of the bolus,with neutralization of its acid component.We also observed that only a third of these clearance events were associated with duodenal pressure waves,suggesting that both the acid and the vol-ume of the bolus often cleared without contractile activity. Numerous previous reports have provided information on duodenal acidi?cation patterns in healthy subjects as well as in patients with peptic ulcer and functional dys-pepsia(2,4,10,27,39,42,52).The pH variations in relation to MMC phases observed in the present study are in accordance with previous reports(3,52,53).We also observed the typical proximal duodenal acid expo-sure pro?le during phase II,with intensive acid exposure occurring in the duodenal bulb(14,52).Studies on prox-imal duodenal acid exposure are technically demanding, requiring either monitoring of the transmucosal potential difference(52)or endoscopical?xation of the probe to a mucosal fold using a hemostatic clip(7)or using Bravo telemetry pH capsules(25).Even slight migration of the probe may lead to large differences in measured acid ex-posure.This may explain part of the discrepancy among the results obtained in previous studies.Prolonged assess-ment of mechanisms involved in the duodenal clearance of endogenous acid is even more challenging,mainly due to dif?culties in studying?uid presence in the duodenum in the interdigestive state.Minimally invasive techniques with which transpyloric and proximal duodenal?uid trans-port can be assessed in humans without?lling the stom-ach with a contrast material have long been lacking.As a consequence,data on transpyloric and proximal duodenal transport and pH variations were limited to animal studies. However,important data have been obtained by implan-tation of electromagnetic?owmeters in dogs by Malbert et al.who have described patterns of duodenal pH drops in relation to transpyloric chyme transport,both in the inter-digestive and in the postprandial period(32,33).Recently several reports have suggested that impedance monitor-ing is an important tool to assess?uid transport in the antroduodenal area(41),distal duodenum(36),and small bowel(22).
The main mechanism of duodenal acid clearance at the proximal duodenal site is the complete clearance of both acid and volume of the bolus.Such clearance does not always imply that the acid is neutralized.Forward trans-port of the acid load contained in the bolus can explain the clearance,and this can occur with or without a con-comitant propulsive pressure event.In fact,in our study, just over a third of these clearance events were associated with a concomitant duodenal contraction.The device used in our study allowed the recording of only three mano-metric signals in the duodenum and some pressure events could have remained undetected by the device.More sen-sitive manometric devices(21,39)or the concomitant use of ultrasound(21,40)may lower the observed rate of passive complete clearance.However,it could be specu-lated that other driving forces bring about?uid movement without occlusive manometrically or ultrasonographically detectable contraction.An antral pump effect has been suggested to explain?ow across the pylorus and in the proximal duodenum(23),and as an open pylorus is the only necessary condition to make?ow from the stomach possible(16,40),small pressure changes in the duodenum may also provide suf?cient force to propel liquid forward in the duodenum.The observation that spontaneous in-terdigestive acidi?cation of the duodenum did not elicit a consistent duodenal motor response was unexpected con-sidering the usual motor response induced by direct acid infusion in the duodenum(17,39,42,48).As a conse-quence,it seems wise to use caution when interpreting results obtained after a so-called physiological exogenous acid load.
In the present study we did not assess directly the role of bicarbonate secretion in the clearance process.How-ever,we observed that the duodenal pH may recover while the impedance remains low,suggesting that the bolus re-mains present but with a higher pH,which may result on mixing with a buffer.It has been reported that the exclu-sion of bile lowered duodenal pH by reducing the buffer-ing capacity of the duodenal juice,but in this model pH drops associated with transpyloric passage of?uid per-sisted,indicating that other sources of alkaline buffer are suf?cient to maintain an almost-neutral pH(32).There are two sources of bicarbonate in the duodenum:from the pancreas,but also directly secreted by duodenal epithe-lial cell(1,18,26).The rapid responsiveness of duode-nal epithelial cells makes the latter an important factor (5).Moreover,relevant alterations of duodenal mucosal bicarbonate secretion are reported in human pathology. Helicobacter pylori infection complicated by duodenal ul-cers is associated with diminished bicarbonate secretion and eradication of Helicobacter pylori infection restores duodenal bicarbonate capacity(19).The observation that duodenal motor activity was absent in all but one of the clearance events with impedance,evidence of persistence of the bolus suggests a role for passive mixing of the acid bolus and locally produced bicarbonate.A concomitant study of fasting gastric acid production and duodenal bi-carbonate secretion showed that these processes are coor-dinated(24).
Pancreatic secretion of bicarbonates is usually closely related to migrating motor complex cycle(8,37,38).Layer et al.reported a correlation between intensity of antral motility and pancreatic secretion during phase II of the
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MMC(29).Three decades ago a pylori–sphincter of Oddi re?ex,probably activated via intrinsic nerves in response to antral motor activity,has been described.This re?ex may serve to optimize the timing of buffer and acid mixing (6),as the Oddi sphincter may open in concert with pyloric opening.
In conclusion,combined pH and impedance recording makes it possible to distinguish between neutralization of acid boluses and their complete total clearance and con-stitutes a useful tool to study physiology and pathophys-iology in the antroduodenal area and potentially also to evaluate the effects of pharmacological intervention.
ACKNOWLEDGMENTS
Guillaume Savoye was supported by grants from Glaxo–Wellcome France and from the National French Society of Gas-troenterology(SNFGE;bourse Robert Tournut).The authors are indebted to Astrid Baron for her valuable technical assistance.
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