Duodenal ulcer: does pathophysiology equal aetiology?

Most discussions about the aetiology of duodenal ulcer depict the duodenal bulb as a battlefield, on which aggressive and defensive factors wage a continuous and continuing campaign for the integrity of the bulbar mucosa. When the scales are tipped in favour of aggression, an ulcer develops. The battlefield is unique, because it is chemical warfare that is usually thought to be taking place hence also the description of the duodenal bulb as the crucible of the alimentary tract. The so-called aggressive factor is usually considered to be gastric juice eroding, or digesting its way into (and through) the duodenal mucosa, while defensive factors are stated to include bicarbonate, which 'neutralises' acid and inactivates pepsin in the duodenal lumen and mucus, which acts as a barrier to acid and pepsin. In addition, the state of the duodenal mucosa is considered to be important, as duodenal ulcers may reflect presumed inadequacy of the mucosa if no other reason can be found for the ulcer. The evidence for this internal turmoil, so often ending in defeat, is epidemiological (identifying groups of individuals at risk) and pathophysiological (indicating which individuals are at risk). The most obviously pertinent epidemiological apparent confirmation that gastric juice is noxious is both positive and derived from the high degree of association between duodenal ulceration and the gastric hypersecretion in patients suffering from gastrinomas,1 as well as negative, because duodenal ulcers do not occur in individuals who secrete no gastric juice at all. The paper by Schulze et al in the present issue of Gut highlights the other aspect of the battle that there are groups of individuals at risk because their defenses are defective because they secrete too little bicarbonate (as a result of pancreatic exocrine insufficiency), or because they have a diseased duodenal mucosa (duodenitis). As the authors (and many others) have pointed out, the association between duodenitis and duodenal ulcer is so controversial as to be aetiologically useless. So is (despite the report of Schulze et at) the association between duodenal ulcer and chronic pancreatitis because this association has also been denied.2 For example, in a large number of patients with chronic pancreatitis the incidence of duodenal ulcers was 2%.3 The epidemiological evidence can therefore be summarised as showing a fairly strong (but not invariable) association between gastrinomas and duodenal ulcers, an association which, it is assumed, is based causally on the gastric hypersecretion evoked by the gastrinoma. An alternative approach to establishing the aetiological involvement of aggressive gastric juice is experimental. After showing that gastric juice digested the legs of frogs and ears from rabbits,4 large amounts of