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Abnormal Gastric Mucosa in Man

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Abnormal Gastric Mucosa in Man Gut: first published as 10.1136/gut.17.12.993 on 1 December 1976. Downloaded from Gut, 1976, 17, 993-997 Potential difference across the normal and the abnormal gastric mucosa in man A. HOSSENBOCUS1, P. FITZPATRICK2, AND D. G. COLIN-JONES From Southampton University Medical School, Southampton SUMMARY The mucosal potential difference in the body ofthe stomach was measured in 18 patients with gastric ulcers, five with gastritis, and three with pernicious anaemia. The results were compared with those of 12 normal volunteers. Significantly lower than normal levels were found in the groups of patients with gastric ulcers and gastritis. The patients with pernicious anaemia had even lower potential differences. In an additional 25 subjects, measurements were made in the duodenal bulb and at five sites in the stomach under direct vision at endoscopy. Biopsies were taken from each site for histology. Subjects with gastritis at the high lesser curve had a significantly lower potential difference at that site than those without gastritis. In the latter group, the potential difference at the high lesser curve was as low as in the antrum, and invariably lower than at the high greater curve. Exposure to eugenol of the gastric mucosa of dogs difference does not suffer from the drawbacks with Heidenhain pouches leads to an increase in the associated with permeability studies, it was used for back-diffusion of hydrogen ions, and to apparent comparing the abnormal gastric mucosa of patients hyposecretion after stimulation with histamine with gastric ulcers, gastritis, and pernicious anaemia (Davenport et al., 1964). The human gastric mucosa with the normal. In an additional group of patients responds similarly to a number of agents, including requiring diagnostic endoscopy, measurements were http://gut.bmj.com/ aspirin (Smith et al., 1971) and bile salts (Ivey made and biopsies taken from specific sites under et al., 1970). Davenport (1965) postulated that the direct vision in order to obtain more direct correla- abnormal gastric mucosa of patients with gastric tion between histology and potential difference. ulcers allowed excessive reabsorption of secreted hydrogen ions, thereby causing apparent hypo- Methods secretion. Permeability studies in gastric ulcer patients have provided some evidence in favour of CONVENTIONAL TECHNIQUE on September 25, 2021 by guest. Protected copyright. this hypothesis (Chapman et al., 1968; Chapman Potential difference was measured by the method of et al., 1972; Ivey and Clifton 1974). However, Anderson and Grossman (1965). The reference problems with recovery of instilled solutions, electrode for intravenous insertion consisted of a neutralisation, secretion, and gastric emptying make fine polyethylene tube (internal diameter 1 14 mm) such studies difficult in man, and the results are containing 3 % agar saturated with potassium sometimes inaccurate. chloride. This was sterilised by gamma radiation. Agents that impair the gastric mucosal barrier The intragastric electrode was a similar tube in man also lower the gastric mucosal potential (internal diameter 3 mm) containing the same difference (Geall et al., 1970; Hossenbocus and material. Potential difference was measured with Colin-Jones, 1975). Studies in animals have shown balanced calomel half-cells (K-100 Radiometer, a correlation between the increased sodium and Copenhagen) and recorded on paper (Servograph hydrogen ion fluxes, and the fall in the potential Pen Drive REA 310, Radiometer, Copenhagen) via difference (Davenport et al., 1964; Chvasta and a pH meter (Titrator TTT 2, Radiometer, Copen- Cooke, 1972). Since measurement of the potential hagen). After an overnight fast, the subject was kept in 'Present address: Princess Alexandra Hospital, Woolloon- the while the electrode was gabba, Brisbane, Queensland, Australia. sitting position exploring "Present address: Queen Alexandra Hospital, Portsmouth, passed orally to about 80 cm. The subject then lay Hants. on his left side, and the reference electrode was Received for publication 26 July 1976 introduced into a peripheral vein via a sterile 993 Gut: first published as 10.1136/gut.17.12.993 on 1 December 1976. Downloaded from 994 A. Hossenbocus, P. Fitzpatrick, and D. G. Colin-Jones Table 1 Highest gastric mucosal potential difference those was: gastric ulcer (five), duodenal ulcer (four), recorded in four normal subjects on two separate pyloric ulcer (two), hiatus hernia (one), no lesion occasions seen (10). Subject Measurement ofPD (-m V) H ISTOLOGY 1 2 Biopsy specimens were fixed in buffered formol 1 45 45 saline and processed routinely. Sections were 2 49 44 with 3 42 43 stained haematoxylin and eosin and examined 4 43 43 by one of us (P.F.) without any knowledge of the potential differences recorded. The recommenda- needle. The circuit was completed, and the exploring tions of Whitehead were followed (Whitehead et al., electrode was withdrawn 5 cm at a time while 1972; Whitehead, 1973). potential difference was recorded continuously. Informed consent was obtained from all 63 The highest potential difference was obtained when subjects studied. The safety of the subject from the tip of the electrode was 45-50 cm from the incisor electrical hazards was ensured by following the teeth. This figure was accepted only if it was steady recommendations in the Hospital Technical Mem- for at least 10 minutes. With this technique there orandum 8 (Department of Health and Social was no need to use fluoroscopy to position the Security, 1969). exploring electrode. The results of a preliminary study in which the potential difference was measured Results on two separate occasions in four normal subjects are shown in Table 1. CONVENTIONAL TECHNIQUE The subjects studied consisted of 12 normal The group of 12 normal subjects had a potential volunteers, 18 patients with benign lesser curve difference of -45-7±0-6 mV. (mean ±SEM) in gastric ulcers, five with atrophic gastritis, and three the body of the stomach. As shown in Table 2, this with treated pernicious anaemia. All the patients with gastric ulcers or gastritis had the diagnosis Table 2 Gastric mucosal potential difference in body confirmed with endoscopy and multiple biopsies. ofstomach in normal subjects Investigators Subjects (no.) PD (-m V) http://gut.bmj.com/ MEASUREMENT UNDER DIRECT VISION Mean+5 EM For measurement of the potential difference at Andersson and 5 43-6 4-7 endoscopy, the conventional technique was modified Grossman Geall et al. 9 35-5 + 0-5 by replacing the exploring electrode with a finer Bennett et al. 5 53-8 2-3 polyethylene tube (internal diameter 1-4 mm) Hossenbocus and 12 45 7 0-6 containing the same material. This was threaded Colin-Jones through the biopsy channel of the GIF D2 (Olympus) endoscope. is similar to the findings of Andersson and Grossman on September 25, 2021 by guest. Protected copyright. After an overnight fast, the patient was pre- (1965) and Bennett et al. (1974), but somewhat medicated with intravenous diazepam in a dose of higher than those of Geall et al. (1970). 20-30 mg. Atropine was not used. The reference The results for all four groups in this study are electrode was inserted in an antecubital vein in the shown in Fig. 1. The patients with gastric ulcers had left arm. During endoscopy, which was carried out a lower potential difference (-32-4 ± 0-7 mV) with the subject lying on his left side, a note was than the normal subjects. Statistical analysis using made as to whether there was bile-stained fluid in the t test showed the difference between the means the stomach. Fluid was sucked out before passing to be significan: (P<0 001). the exploring electrode through the biopsy channel. The mean for the patients with gastritis, - 33-6 mV, The tip was pressed gently against the mucosa, and was also significantly lower (p <0-01) than that for the potential difference was recorded for one minute. the normal group. Measurements were made in the duodenal bulb, The group of patients with pernicious anaemia the prepyloric region, at the incisura, the low greater was too small for statistical analysis. However, all curve, the high lesser curve, and the high greater three patients had potential differences (-35, -29 curve. Biopsies were then taken from each one of and -23 mV) lower than -37 mV, the lowest those sites. level recorded in the group of normal subjects. Twenty-five subjects needing diagnostic endo- scopy were studied. Technically satisfactory tracings MEASUREMENT UNDER DIRECT VISION were obtained in 22. The endoscopic diagnosis for As bile salts increase the permeability of the gastric Gut: first published as 10.1136/gut.17.12.993 on 1 December 1976. Downloaded from Potential difference across the normal and the abnormal gastric mucosa in man 995 Normal Gastric Gastritis Pernicious curve, the antrum, and, to a lesser extent, the high mV Subjects Ulcer Anaemia -60 -457±06 -32 4±007-33 6±14 -29 greater curve, were also affected. Twelve subjects had a normal or near-normal mucosa at the high lesser curve. The distribution -501 of the potential difference is shown in Fig. 3. The -401 -30 I -15-8± 22- -201. -10 2-3 oL I Fig. 3 Potential difference in mV) in Fig. 1 Potential difference in the body of the stomach (mean±SEM in normal volunteers and in three groups ofpatients. the duodenal bulb and at five sites in the stomach in (Mean and SE at top of each column.) 12 subjects with normal high lesser curve. mucosa (Ivey et al., 1970; 1971), and lower the Table 3 Potential difference at high lesser curve and potential difference (Geall et al., 1970), subjects high greater curve in subjects with normal gastric with appreciable amounts of bile-stained fluid in mucosa the stomach were placed in a separate group. All Subject Potential difference (-m V) four of them had very low potential differences.
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