The Acid Pocket: A Target for Treatment in Reflux Disease?

Kahrilas, Peter J.; McColl, Kenneth E.L.; Fox, Mark; O’Rourke, Lisa; Sifrim, Daniel; Smout, A. J. P. M.; Boeckxstaens, Guy E.

doi:10.1038/ajg.2013.132

Cited by 133 publications

(96 citation statements)

References 52 publications

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“…Recent evidence indicates that it is the acidity of the gastric contents close to the gastro-oesophageal junction (GEJ), referred to as the acid pocket, which refluxes and causes oesophageal damage 8. It is also known that loss of gastric secretory cells due to H. pylori induced atrophic gastritis does not occur uniformly throughout the stomach but may be more marked at the periphery of the acid-secreting mucosa 9.…”

Section: Introductionmentioning

confidence: 99%

The gastric acid pocket is attenuated inH. pyloriinfected subjects

Mitchell

Derakhshan

Wirz

et al. 2016

Gut

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Objective: Gastric acid secretory capacity in different anatomical regions, including the postprandial acid pocket, was assessed in H. pylori positive and negative volunteers in a Western population. Design:We studied 31 H.pylori positive and 28 H.pylori negative volunteers, matched for age, gender and BMI. Jumbo biopsies were taken at 11 pre-determined locations from the gastroesophageal junction and stomach. Combined high resolution pHmetry (12 sensors) and manometry (36 sensors) was performed for 20 minutes fasted and 90 minutes postprandially. The squamocolumnar junction was marked with radio-opaque clips, and visualised radiologically. Biopsies were scored for inflammation and density of parietal, chief and G cells immunohistochemically.Results: Under fasting conditions, the H.pylori positives had less intragastric acidity compared to negatives at all sensors >1.1cm distal to the peak lower oesophageal sphincter (LES) pressure (p<0.01). Postprandially, intragastric acidity was less in H.pylori positives at sensors 2.2, 3.3 and 4.4cm distal to the peak LES pressure (p<0.05), but there was no significant differences in more distal sensors. The postprandial acid pocket was thus attenuated in H.pylori positives.The H.pylori positives had a lower density of parietal and chief cells compared to H.pylori negatives in 10 of the 11 gastric locations (p<0.05). 17/31 of the H.pylori positives were CagA seropositive and showed a more marked reduction in intragastric acidity and increased mucosal inflammation. Conclusion:In population volunteers, H.pylori positives have reduced intragastric acidity which most markedly affects the postprandial acid pocket.

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Section: Introductionmentioning

confidence: 99%

The gastric acid pocket is attenuated inH. pyloriinfected subjects

Mitchell

Derakhshan

Wirz

et al. 2016

Gut

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“…A similar effect has been reported in humans, both pre and post-prandial, when intra-gastric pH is measured in multiple locations [111]. Regional pocketing of acidity has been described in humans [112] and appears to warrant further investigation in the horse, especially when monitoring response to treatment with acid suppressive agents as this was when the differences between the two measurement points were most obvious (data not shown). The %t>pH4 and median intra-day pH for measurement point 1 were consistently higher than measurement point 2,…”

Section: Discussionsupporting

confidence: 48%

Factors affecting the pharmacokinetics and pharmacodynamics of omeprazole in the horse

Sykes¹

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Equine Gastric Ulcer Syndrome (EGUS) is a common condition of the horse, affecting a broad range of horse usages and types. Recently the terminology of the syndrome has been expanded to include terms Equine Squamous Gastric Disease (ESGD) and Equine Glandular Gastric Disease (EGGD) to describe diseases of the squamous and glandular mucosa of the stomach, respectively. Omeprazole, a proton pump inhibitor that blocks acid production, is considered the treatment of choice for EGUS and it has been widely used for this purpose for nearly 20 years. Yet, surprisingly, despite its widespread use little is known about the factors that affect its efficacy, such as the impact of formulation, diet and dose. Further, although it is commonly believed that the once daily administration of omeprazole results in durations of acid suppression exceeding 24 hours, there is conflict in the literature as to the validity of this belief. Recent clinical studies have demonstrated that the healing rate for EGGD is inferior to that of ESGD, raising further questions as to the efficacy of omeprazole under clinically relevant conditions. One potential reason for this observation is that the duration of intra-day acid suppression required for healing of ESGD may be less than that for EGGD. This, coupled with the possibility that once daily administration of omeprazole may not result in acid suppression for the entire 24 hour treatment interval, provides a potential explanation for the poor EGGD healing rates that have been recently reported. The purpose of this thesis was to investigate the factors that affect the efficacy of omeprazole in the horse. The studies were conducted in four parts; firstly, the effect of formulation and diet on the pharmacokinetics of omeprazole were investigated; secondly, a model that allows continuous intra-gastric pH measurement under clinically relevant conditions was developed; thirdly, the impact of diet and dose on the pharmacokinetics and pharmacodynamics of omeprazole were investigated; and lastly, the relationships between key pharmacokinetic and pharmacodynamic variables were investigated. The findings of the study suggested that some method of physical protection is required to protect the omeprazole from degradation in the acidic environment of the stomach and to improve bioavailability. However, significant differences were not present between formulations utilising the two most common forms of protection, namely the use of enteric coated granules in paste or buffering of the formulation. This suggests that the method of protection, buffering of the formulation or the use enteric coated granules in paste, used is less important than protection per se. The earlier studies of the thesis 3 suggested that an effect of feeding may be present on the pharmacokinetics of omeprazole but a statistically significant effect could not be demonstrated. Similarly, the latter studies suggested that diet may play a role in bioavailability with ad libitum roughage diets impairing absorption, but no statistically signi...

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“…This was first demonstrated in 2001 by investigators using a stepwise pull through of a pH catheter from the proximal stomach across the EGJ in the postprandial state [87]. In patients with GERD, the acid pocket may act as a reservoir for reflux into the esophagus, potentially leading to symptoms or mucosal injury [88]. When compared to healthy volunteers, patients with GERD have increased acid pocket length, as well as a more proximal location of the acid pocket within a hiatal hernia [89].…”

Section: Barium Radiographymentioning

confidence: 98%