Mertz H R, Walsh J H
Department of Medicine, University of California, School of Medicine, Los Angeles.
Med Clin North Am. 1991 Jul;75(4):799-814. doi: 10.1016/s0025-7125(16)30412-6.
Despite extensive research, the etiology of peptic ulcer disease remains unclear. Given the multiple processes that control acid and pepsin secretion and defense and repair of the gastroduodenal mucosa, it is likely that the cause of ulceration differs between individuals. Acid and pepsin appear to be necessary but not sufficient ingredients in the ulcerative process. It is clear that the majority of gastric ulcers and a substantial number of duodenal ulcers do not have increased gastric acid secretion. Recent research has focused more on protection and repair of the stomach and duodenum. NSAIDs cause a significant number of gastric and duodenal ulcers; this is probably due to inhibition of prostaglandin production with loss of its protective effects. In the absence of NSAIDs and gastrinoma, it appears that most gastric ulcers and all duodenal ulcers occur in the setting of H. pylori infection. Evidence is mounting in support of H. pylori as a necessary ingredient in the ulcerative process, similar to acid and pepsin. It is not known whether the bacteria or the accompanying inflammation is the more important factor in the pathophysiology. Although the pathophysiology of gastric ulcer and duodenal ulcer is similar, there are clearly differences between the two groups. Duodenal ulcer is typified by H. pylori infection and duodenitis and in many cases impaired duodenal bicarbonate secretion in the face of moderate increases in acid and peptic activity. These facts suggest the following process: increased peptic activity coupled with decreased duodenal buffering capacity may lead to increased mucosal injury and result in gastric metaplasia. In the presence of antral H. pylori, the gastric metaplasia can become colonized and inflamed. The inflammation or the infection itself then disrupts the process of mucosal defense or regeneration resulting in ulceration. A cycle of further injury and increased inflammation with loss of the framework for regeneration may then cause a chronic ulcer. Gastric ulcer often occurs with decreased acid-peptic activity, suggesting that mucosal defensive impairments are more important. The combination of inflammation, protective deficiencies, and moderate amounts of acid and pepsin may be enough to induce ulceration. Many questions remain in understanding the pathophysiology of peptic ulcer disease. The physiology and pathophysiology of mucosal regeneration and the mechanisms by which H. pylori and inflammation disrupt normal gastroduodenal function will be fruitful areas of future investigation.
尽管进行了广泛的研究，但消化性溃疡病的病因仍不清楚。鉴于控制胃酸和胃蛋白酶分泌以及胃十二指肠黏膜防御和修复的过程多种多样，溃疡形成的原因在个体之间可能有所不同。胃酸和胃蛋白酶似乎是溃疡形成过程中必要但不充分的因素。显然，大多数胃溃疡和相当数量的十二指肠溃疡患者胃酸分泌并未增加。最近的研究更多地集中在胃和十二指肠的保护与修复方面。非甾体抗炎药（NSAIDs）会导致大量的胃和十二指肠溃疡；这可能是由于其抑制前列腺素生成并丧失了保护作用。在没有NSAIDs和胃泌素瘤的情况下，似乎大多数胃溃疡和所有十二指肠溃疡都发生在幽门螺杆菌感染的背景下。越来越多的证据支持幽门螺杆菌是溃疡形成过程中的必要因素，类似于胃酸和胃蛋白酶。目前尚不清楚细菌或伴随的炎症在病理生理学中哪个更为重要。尽管胃溃疡和十二指肠溃疡的病理生理学相似，但两组之间显然存在差异。十二指肠溃疡的典型特征是幽门螺杆菌感染和十二指肠炎，在许多情况下，面对胃酸和胃蛋白酶活性的适度增加，十二指肠碳酸氢盐分泌受损。这些事实提示了以下过程：胃蛋白酶活性增加加上十二指肠缓冲能力下降可能导致黏膜损伤增加并导致胃化生。在胃窦部存在幽门螺杆菌的情况下，胃化生可被定植并发生炎症。炎症或感染本身随后会破坏黏膜防御或再生过程，导致溃疡形成。进一步损伤和炎症增加以及再生框架丧失的循环可能会导致慢性溃疡。胃溃疡常伴有胃酸 - 胃蛋白酶活性降低，这表明黏膜防御功能受损更为重要。炎症、保护功能缺陷以及适量的胃酸和胃蛋白酶的共同作用可能足以诱发溃疡形成。在理解消化性溃疡病的病理生理学方面仍存在许多问题。黏膜再生的生理学和病理生理学以及幽门螺杆菌和炎症破坏正常胃十二指肠功能的机制将是未来研究富有成果的领域。
