710 GASTRIC EMPTYING IN DUODENAL ULCER DISEASE

Occasional

Survey

PEPTIC ULCER AND THE PYLORUS* ALAN G. JOHNSON

Department of Surgery, Charing Cross Hospital Medical School, London MOST gastric and duodenal ulcers occur in the intermediate zone between where acid is secreted (the body and fundus of the stomach) and where alkaline juice enters the second part of the duodenum. In the middle of this zone lies the pylorus, separating the stomach with a mucosa highly adapted to withstand acid, from the duodenum with a mucosa adapted to withstand bile and pancreatic juice (fig. 1). It seems likely that the pylorus is important in controlling the mixing of these two very different secretions; if too much acid is allowed into the duodenum too quickly it could produce duodenal ulcers,

of the pylorus in relation secretions and sites of ulcers.

Fig. I-Key position

to

mixing

of

and if too much bile and pancreatic juice refluxes into the stomach, and stays there, this could cause gastric ulceration. What evidence is there that the direction and rate of movement of the upper gastrointestinal secretions is important in the pathogenesis of ulcers? What role does the pylorus play in controlling these movements? What alterations in the movements, as well as secretions, are

produced by surgery? NORMAL PYLORIC AND GASTRIC MOTOR FUNCTION

pylorus is believed to have the following functions-(1) to limit the passage of particles over a certain size, (2) to stop the flow of chyme by closing the end of an antral contraction, and (3) to prevent duodenogastric reflux. Initial emptying of liquids occurs as a cascade into the duodenum and depends on the static pressure of the fundus and body of the stomach. Later emptying of liquids and emptying of solids depends on active antral The

contractions. *Based on the 31st Simpson Smith Memorial Lecture, West London Hospital, Oct. 11, 1978.

A duodenal ulcer is not just the result of a certain level of acid secretion since there is considerable overlap between the peak acid output of normal subjects and that of people with duodenal ulcer. Many factors probably contribute to the final ulceration. Mucosal resistance is obviously important, but the rate at which acid is delivered to the duodenum and then neutralised needs to be considered. There is evidence that gastric emptying of a buffered meal in duodenal-ulcer patients occurs twice as fast as in normal controls.2 The acid might not be so thoroughly mixed and buffered by food, and this could result in a sudden acid load passing to the duodenum at the end of gastric emptying. The length of time acid stays in the duodenal cap and the extent to which it is mixed with the alkaline duodenal juice depends on the motility patterns of the duodenum, which will be discussed later. Although the motility of the pyloric region is by no means the only factor in duodenal-ulcer disease, it may at times be a key factor.

MOTILITY AFTER

SURGERY FOR DUODENAL ULCER

Abnormalities in motility and the mixing of gastric and duodenal contents are side-effects of all operations for duodenal ulcer. Some, such as Polya gastrectomy which bypasses the duodenum and removes the antrum, produce major anatomical changes, but I will discuss two common operations which cause less anatomical alteration. Any operation in which the fundus is denervated causes a failure of adaptive relaxation, which leads to a full feeling after normal-sized meal$which persists for weeks or months. Truncal vagotomy and pyloroplasty.-This procedure increases initial gastric emptying of liquids in two ways-i.e., by reducing the adaptive relaxation of the fundus and by widening the pylorus. In this situation of "partial gastric incontinence" the patient’s position is important, liquid emptying being slowed when he is lying on his left side.3 Gastric emptying of solids however, depending as it does on antral contractions, is delayed after truncal vagotomy even though the pylorus has been widened by a pyloroplasty. This explains why the same patient may experience symptoms of both dumping and delayed gastric emptying.4 Proximal gastric vagotomy also speeds liquid emptying a little because of the absence of fundal relaxation, but the antro/pyloric mechanism is still intact and so the cascade effect is not so great. Emptying of solids is nearly normal. Late emptying of liquids was investigated in 4 groups of patients, those having total gastric vagotomy with and without pyloroplasty or proximal gastric vagotomy with and without pyloroplasty. Only the patients with proximal gastric vagotomy and no pyloroplasty (an innervated antrum and intact pylorus) had normal gastric emptying. A follow-up study6 of 32 patients with pyloroplasty alone demonstrated that the incidence of dumping and diarrhoea was similar to that in those who had had a truncal vagotomy and pyloroplasty. It seems, then, that an intact pyloric mechanism is the key factor in preventing side-effects after vagotomy for duodenal ulcer.’ The importance of the pylorus in selecting particle size is shown by the bolus obstruction which may

711

occasionally pylorus.

occur

after division

or

bypass

of the

GASTRIC ULCERATION

There is good evidence that duodenogastric reflux is greater in patients with gastric ulceration than in normal controls. The harmful effect of bile in the stomach is not a new concept-it was pointed out by John Hunter 200 years ago-and it has been increasingly studied over the last 20 years.8-11 Although the incompetence of a grossly scarred pylorus is understandable, why does an apparently normal pylorus (in type-l gastric ulcer) allow reflux? It may be the result of a defect either in the pylorus itself or in the coordination of contractions each side of it. Abnormal pyloric contraction.-Fisher and Cohen12 suggested that in gastric ulceration the pylorus does not contract normally in response to cholecystokinin (c.c.K.) and secretin. This evidence was collected during experiments in which open-tipped catheters were pulled through the pylorus with the patient lying on the right side. We have repeated this work at endoscopy, measuring the resting pyloric diameter between contractions with a calibrated balloon under direct vision with the patient supine." Fig. 2 shows typical changes in pyloric diameters after a bolus injection of 1 unit/kg c.c.K. 11’1,

TIME (min) AFTER C C K GIVEN

Fig. 2-Typical changes in pyloric diameter in a normal subject and a gastric-ulcer patient in response to i.v. bolus of C.C.K. (1 U/kg). Dotted line

at

2

mm

represents diameter of catheter around which

pylorus was tightly closed.

(Karolinska). Although the mean pyloric diameter of 10 gastric-ulcer patients was larger than those of 10 normal and 10 duodenal-ulcer patients, the response of those with a gastric ulcer was slightly greater than normal. C.C.K. contracts the pylorus and inhibits the antrum. Glucagon does the same but pentagastrin contracts the pylorus while enhancing or not altering the antral contractions. The full gastrin molecule has not been studied but it may relax the sphincter while enhancing the antral contractions. It seems, then, that failure of the pylorus to respond to gastrointestinal hormones is an inadequate explanation for abnormal pyloric contraction in patients with gastric ulceration. In any case, a long sustained tonic contraction of the pylorus as produced by such hormones, would not make physiological sense, because the pylorus must open during antral contractions to allow the stomach to empty. The resting dia-

Fig.

3-Pressure recordings at different times in same patient, from antrum (A), first part of duodenum (Dl), and second part of duodenum (D2).

A

no reflux, and C reflux with rapid indicate direction of flow of duodenal contents.

reflux, B

arrows

emptying. Open

meter of the pylorus may vary in response to hormones rather as the iris of the eye varies in diameter under different stimuli, and the larger diameter in patients with gastric ulcer could be the result of higher fasting gastrin levels which Rovelstadl4 suggests may explain many features of gastric ulcer. The diameter of the pylorus may regulate the amount of chyme that passes through

it in either direction; but what really matters in prevention of reflux is the timing of its complete closure, because only complete closure will prevent reflux. During emptying it normally closes at the end of an antral contraction and the duodenal cap contraction occurs while it is closed. However, if the duodenal contraction occurs while the pylorus is open, reflux may follow. Abnormalities of antral and duodenal contractions.-Patients were studied by synchronous radiology and pressure measurements by means of a Honeywell motility probe (model 31) positioned with transducers in the antrum and duodenum. The recordings of both movement of barium and pressure were recorded via a video-mixer onto videotape. 15 The recording periods were short to avoid significant radiation but three contraction patterns were associated with reflux. 1. Retroperistaltic waves originating in the 2nd part of the duodenum regularly produced reflux provided there was not an antral contraction which happened to close the pylorus. Fig. 3A shows a tracing of a retroperistaltic wave which produced reflux because there was no antral contraction. Fig. 3B shows a tracing of a retroperistaltic wave which did not produce reflux because an antral contraction happened to arrive at the right time and close the pylorus. Fig. 3C shows a tracing of a retroperistaltic wave in which the refluxed contents were quickly emptied by a subsequent antral contraction. All these tracings are from the same patient during a 5 min

recording period. 2. Sometimes a duodenal cap contraction started distally than normal and the contents were sent

more

distally and proximally at the same time. 3. Occasionally a patulous pylorus failed to close completely with an antral contraction. This was shown by positioning, under X-ray control one of the transducers actually in the pyloric canal. This may link up with the finding that gastric ulcer patients have a wide resting pyloric diameter.

712 It seems from patterns 1 and 2 that the site of origin and direction of propagation, as well as the timing of duodenal contractions, are important in reflux: if a duodenal cap contraction starts just next to the pylorus and is propagated distally, the contents will probably not reflux, even in the absence of an antral contraction. A retroperistaltic contraction on the other hand starting in the 2nd part of the duodenum will push the contents in front of the contraction ring and so the pyloric part of the duodenum will not be closed until after reflux has occurred. Experimental pacing in animals.-To test these conclusions we arranged experiments in cats with chronically implanted stimulating and recording electrodes in the antrum and duodenum, and an indwelling cannula in the second part of the duodenum for introducing contrast medium. Unlike the human subjects, the cats had no tube crossing the pylorus itself and the preparation differed from Kelly’s dog modelI6 in that more than one electrode could be stimulated at once. Synchronous radiological and electrical activity was recorded on video-tape. The preliminary results17 can be summarised as follows :-

Pacing of the 2nd part of the duodenum at its basic 15-16/min rate produced retroperistaltic contraction

in the stomach is obviously important and reflux may be of very little clinical importance if strong antral contractions empty the bile rapidly. ROLE OF STRESS IN OVERALL CONTROL

What produces these abnormalities of motility? Local irritation can produce ectopic pacemaker sites and concentrated bile itself arriving in the duodenum may stimulate contractions. Gastrointestinal hormones play their part. An active duodenum, open pylorus, and inhibited antrum are the changes par excellence that produce reflux and these same changes which also occur at the start of the vomiting reflex could represent "subthreshold vomiting". A certain combination of hormone levels could produce these changes, but central nervous control is also important. Stress inhibits the stomach and produces bile reflux in peptic-ulcer patients. Stress could cause gastric ulcer through parasympathetic, sympathetic, and dopaminergic2O control of motility. Although much is still speculation, a mechanism can now be visualised by which central stimuli could produce ulcers irrespective of their effect on acid secretion. CONCLUSIONS

1.

and consistent reflux into the stomach in all 4 cats. This did not occur in the absence of pacing. 2. Synchronous pacing of the proximal duodenum reduced the percentage of duodenal contractions that produced reflux but did not abolish reflux. 3. Synchronous pacing of the antrum or its stimulation with metoclopramide again reduced but did not abolish reflux. The most noticeable feature however was the rapid emptying of any refluxed contents by the strong antral contractions. This had been observed in _

patients. 4. If distal pacing sometimes resulted. In

was

continued

too

long, vomiting

does not see retroperistaltic contractions at the highest natural contraction rate (11/min) but Kilby in his original observationsl8 did find (in duodenal-ulcer patients) that those with reflux had a significantly higher proportion of retroperistaltic contractions than those who did not. These experiments suggest that retroperistaltic duodenal contractions in the absence of strong antral or proximal duodenal contractions are the key abnormality in duodenogastric reflux. They seem to differ from the to-and-fro mixing movements commonly seen in the second part of the duodenum. man one

DELAYED GASTRIC EMPTYING AND EFFECTS OF REFLUX

There is good evidence that gastric ulcer may be secondary to pyloric stenosis or delayed gastric emptying after truncal vagotomy without adequate drainage. 19 However, the evidence that type-i gastric ulcer patients usually have delayed emptying is not so strong. I do not recognise the supposed conflict between the two theories of bile reflux and delayed emptying-since they occur together with pyloric scarring and, as we have seen, the motility changes that produce most reflux are also those that tend to delay emptying. In terms of any damage to the gastric mucosa, the length of time that bile remains

Disorders of the pyloric mechanism are important in understanding the cause and methods of treatment of peptic ulcer, but concentration on the pylorus itself has taken attention away from what is happening either side of it, particularly in the duodenum. An understanding of duodenal control mechanisms may well provide the key to the cause of reflux. However, it is unlikely that one single factor is responsible for the motility disorders in either duodenal or gastric ulcers. It is more likely that there is an alteration in the delicate balance of neural and hormonal control of the stomach and duodenum, that in some patients leads to mild dyspeptic symptoms but in others is severe and prolonged enough to produce frank ulceration. I thank Mr C. J. C. Kirk and the staff of the Department of Surgery, Charing Cross Hospital Medical School, for technical advice and help throughout these studies, Mr Stewart Ganley and the Department of Medical Illustration for the figures, and Miss C. Hutchings for secretarial assistance.

REFERENCES 1. 2. 3. 4.

Code, C. F., Rendic, R. Gastroenterology, 1970, 2, 20. Fordtran, J. S., Walsh, J. H. J. clin. Invest. 1973, 52, 645.

McKelvey, S. T. D. Br. J. Surg. 1970, 57, 741. Donovan, I. A., Keighley, M. R. B., Griffin, D. W., Harding L. K., Alexander-Williams, J. ibid. 1976, 63, 349. 5. White, C. M., Poxon, V., Keighley, M. R. B., Alexander-Williams, J. Gut, 1978, 19, A977. 6. Douglas, M., Duthie, H. L. Br. J. Surg. 1972, 59, 783. 7. Johnston, D., Gohgher, J. C. Surg. Clins N. Am. 1976, 56, 1313. 8. Capper, W. M. Ann. R. Coll. Surg. Engl. 1967, 40, 21. 9. Rhodes, J., Barnardo, D. E., Phillips, S. F., Rovelstad, R. A., Hofman, A. F. Gastroenterology, 1969, 57, 241.

10. Du Plessis, D. J. Lancet, 1965, i, 974. 11 Johnson, A. G., McDermott, S. J. Gut, 1974, 15, 710. 12. Fisher, R. S., Cohen, S. New Engl. J. Med. 1973, 288, 273. 13. Munk, J. F., Gannaway, R. M., Hoare, M., Johnson, A. G. in Gastrointestinal Motility in Health and Disease (edited by H. L. Duthie); p. 349. Lancaster, 1978.

14. Rovelstad, R. A. Am. J. dig. Dis. 1976, 21, 165. 15. Johnson, A. G. Ann. R. Coll. Surg. Engl. 1975, 56, 69. 16. Kelly, K. A., Code, C. F. Gastroenterology, 1977, 72, 429. 17. Munk, J. F., Hoare, M., Kirk, C. J. C., Johnson, A. G. Gut, 1978, 19, abstr, 996. 18. 19. 20.

Kilby, J. M.S. thesis, University of London, 1970. Dragstedt, L. R. Am. J.Surg. 1978, 136, 286. Valenzuela, J. E. Gastroenterology, 1976, 71, 1019.

Peptic ulcer and the pylorus.

710 GASTRIC EMPTYING IN DUODENAL ULCER DISEASE Occasional Survey PEPTIC ULCER AND THE PYLORUS* ALAN G. JOHNSON Department of Surgery, Charing Cros...
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