Gerd: increased gastric acid secretion as a possible cause of gerd
Increased gastric acid secretion as a possible
cause of GERD
Jerry D. Gardner
Many experts maintain that gerD is caused by dysfunction of the gastroesophageal barrier and that gastric acid secretion is not the primary underlying defect. By contrast, a recent study by reimer and colleagues raises the possibility that increased gastric acid secretion is an important cause of gerD.
reimer and colleagues1 report results from
treatment is stopped, the increased numbers
of parietal and enterochromaffin cel s then
stopping the PPi would lead to increased
controlled study of healthy individuals who
amplify the effects of normal physiologic
symptoms of GerD, reimer et al.
received 40 mg daily doses of the PPi eso-
stimuli on gastric acid secretion. the results
standably, did not measure 24 h gastric and
meprazole or placebo for 8 weeks, followed
esophageal pH at baseline and after with-
by placebo for 4 weeks in both groups. of
also support the hypothesis that the symp-
59 individuals who received esomeprazole,
toms of GerD can be triggered in healthy
gastric acidity and increased esophageal
26 (44%) experienced at least one episode of
individuals simply by increasing gastric
acid exposure. interpretation of the authors’
clinical y significant heartburn, dyspepsia
findings, therefore, depends critically on
or acid regurgitation during weeks 9–12, in
two important studies that assessed changes
contrast with nine of 59 (15%) individuals
in basal and gastrin-stimulated gastric acid
who received placebo. at weeks 10, 11 and
esophageal barrier and that gastric acid
secretion in healthy individuals before and
12 the percentage of individuals with clini-
after 8 weeks of daily treatment with 40 mg
cally significant heartburn, dyspepsia or
defect.2 a few studies have, however, raised
omeprazole, another PPi.3,4 evidence for
acid regurgitation was 21–22% for the eso-
the possi bility of a link between increased
rebound hypersecretion of gastric acid from
meprazole group and 2–7% for the placebo
gastric acid secretion and GerD,2 but the
these studies was not strong10 and although
importance of these findings has been diffi-
both studies showed a significant increase in
tions at weeks 4 and 8 were significantly
cult to determine and they have been largely
gastrin-stimulated gastric acid output, only
higher in the esomeprazole group than in
ignored. although one study reported that
one8 showed a signifi cant increase in basal
the placebo group, although all values were
basal or pentagastrin-stimulated gastric acid
acid output after omeprazole treatment.
secretion in esophagitis was compar able
gastric concentrations in the esomeprazole
to that in unspecified medical conditions
group returned to baseline after treatment
without esophagitis,5 other studies have
was stopped. Fasting plasma concentrations
reported increased basal, peak or maximal
tively (Figure 1; even though the authors
of chromogranin a, an indirect measure of
gastric acid secretion in patients with GerD
report that 12 indivi duals were studied
enterochromaffin cell mass, were signifi-
compared with that in healthy individuals.6–8
for gastrin- stimulated acid output, i could
cantly higher at weeks 8 and 12 in indivi-
meal-stimulated gastric acid secretion and
only find data for 11 individuals in Figure 2
postprandial gastric acidity were also found
of their article).8 15 days after the 8-week
to be significantly increased in patients with
stopped, 10 individuals showed an increase
and two showed a decrease in basal gastric
since not al individuals experienced acid-
acid output (Figure 1a), while 10 indivi-
with eso meprazole resulted from rebound
hyper secretion of gastric acid that occurred
a decrease in gastrin-stimulated gastric
after the PPi treatment was stopped.2–4 the
acid output (Figure 1b). the study did not
explana tion for rebound acid hyper secretion
all treated individuals, might only trigger
include a control group of indivi duals receiv-
is that PPis cause hypergastrinemia, which
clinical y rele vant symptoms in those with
ing placebo. if it had, one would expect that
in turn causes hyperplasia of gastric parietal
pre- existing lower esophageal sphincter
half of the participants, on average, would
cells (which secrete acid) and also hyper-
dysfunction and a predisposition to reflux.
have higher gastric acid output and half
an equal y likely explanation is that only a
would have lower output than their corre-
mediate the action of gastrin on acid secre-
fraction of individuals experienced rebound
sponding baseline output. in that case, the
differences in gastric acid output between
nature reviews | gastroenterology & hepatology
volume 7 | marCH 2010 | 125
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The author declares an association with the following company: science for Organizations. see
the article online for full details of the relationship.
1. Reimer, C., søndergaard, B., Hilsted, L. &
Bytzer, P. Proton-pump inhibitor therapy induces
acid-related symptoms in healthy volunteers
after withdrawal of therapy. Gastroenterology
2. McColl, K. e. & Gillen, D. evidence that proton-
pump inhibitor therapy induces the symptoms it
is used to treat. Gastroenterology
3. Gillen, D., wirz, A. A., Ardill, J. e. & McColl, K. e.
Rebound hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori
| Gastric acid output measured at baseline and 15 days after stopping 8 weeks of
treatment with omeprazole in healthy individuals not infected with Helicobacter pylori
4. Gillen, D., wirz, A. A. & McColl, K. e.
above the diagonal line (identity line) indicate that the value after omeprazole treatment is
Helicobacter pylori eradication releases
higher than the corresponding baseline value and points below the identity line indicate the
prolonged increased acid secretion following
opposite. The magnitude of the difference between post-omeprazole and baseline values is
omeprazole treatment. Gastroenterology
given by either the vertical or the horizontal distance between the point and the identity line.
5. Hirschowitz, B. i. A critical analysis, with
| Basal gastric acid output, 12 individuals. b
| Gastrin-stimulated gastric acid output, 11
appropriate controls, of gastric acid and pepsin
individuals. values were estimated from Figures 1 and 2 in Gillen et al.
secretion in clinical esophagitis. Gastroenterology
101, 1149–1158 (1991).
6. Collen, M. J., Lewis, J. H. & Benjamin, s. B.
controls would not be significant because of
of treatment with either a PPi or placebo.
Gastric acid hypersecretion in refractory gastroesophageal reflux disease.
the small sample size (P
= 0.19 and P
the authors found that the prevalence of
98, 654–661 (1990).
calculated by Fisher’s exact test, for basal
clinical y relevant heartburn, dyspepsia or
7. Collen, M. J. & Johnson, D. A. Correlation
and gastrin-stimulated gastric acid output
acid regurgitation was significantly higher
between basal acid output and daily ranitidine
after stopping the PPi than after stopping
dose required for therapy in Barrett’s esophagus. Dig. Dis. Sci.
37, 570–576 (1992).
that half of the individuals receiving placebo
placebo. these findings raise the possibil-
8. Johansson, K. e., Ask, P., Boeryd, B.,
would show an increase in basal acid output
ity that increased gastric acid secretion is a
Fransson, s. G. & Tibbling, L. Oesophagitis,
and in gastrin-stimulated acid output after
signs of reflux, and gastric acid secretion in patients with symptoms of gastro-oesophageal
the placebo was stopped, a sample size of
Future studies should try to measure symp-
reflux disease. Scand. J. Gastroenterol.
40 in each group would be required to have
90% power to detect the increase in basal
expand on the very important findings by
9. Gardner, J. D., sloan, s., Miner, P. B. Jr &
Robinson, M. Meal-stimulated gastric acid
acid output illustrated in Figure 1a with a
secretion and integrated gastric acidity in
signifi cance level of 0.05. similarly, a sample
gastro-oesophageal reflux disease. Aliment.
size of 25 in each group would be required
Science for Organizations Inc., 75 DeSilva
17, 945–953 (2003).
Island Drive, Mill Valley, CA 94941, USA.
to have 90% power to detect the increase in
10. Hunfeld, n. G., Geus, w. P. & Kuipers, e. J.
systematic review: rebound acid hypersecretion
gastrin-stimulated acid output illustrated
after therapy with proton pump inhibitors.
in Figure 1b with a significance level of 0.05.
Aliment. Pharmacol. Ther.
25, 39–46 (2007).
the six points closest to the identity line
in Figure 1a or the five points closest to
the identity line in Figure 1b represent
Bacterial clearance in Crohn’s
acid output that would be likely to induce
these results suggests that only a fraction
of the individuals treated with the PPi in
fested acid-related symptoms because they
evidence from a recent study strongly implicates innate immunity in the
were the only participants that developed
etiology of Crohn’s disease, with particular focus on impaired secretion
a suffi ciently high rebound gastric acid
of cytokines and chemokines by intestinal macrophages in response
hyper secretion to lead to an increase in
to bacterial stimuli. these findings highlight the importance of acute
inflammatory responses in the first stages of disease pathogenesis.
induced rebound gastric acid hypersecretion
have lacked appropriate control groups.10
Crohn’s disease is a chronic form of iBD
that affects one in 1,000 adults. owing to its
characteristic inflammatory symptoms are,
however, known to arise from defects in the
ing gastroesophageal symptoms in healthy
lying the initial manifestation of disease
epithelial barrier and the mucosal immune
| MARCH 2010 | voluMe 7
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“JAWS” Attacks On The Daubert Trilogy A Case Study: The Parlodel® Litigation Stephen D. Otero is a senior associate in the Richmond office of Troutman Sanders LLP He is a graduate of the University of Virginia (B.A 1989) and William & Mary Law School (J.D. 1995), where he was a member of the William & Mary Law Review and the Moot Court Board. Since completing a cler
Team: Lidingö sjukhem Syfte med deltagandet i Genombrott: Teammedlemmar: 1. Att skapa en meningsfull och harmonisk 2. Minska oro, förtvivlan och aggression hos Ssk, MS, Ed.D en utvald grupp boende. Population: Arbetet riktade sig primärt mot nio permanent Arbetsterapeut boende (6♂ & 3♀) på en demensavdelning Ssk2.lidingö@actica.se bestående av 30 boende totalt. Vas