Pathogenesis of Peptic Ulcer

About a third of the patients with duodenal ulcer suffer from an excess secretion of gastric acid. This may be due to an increase in the mass of acid-secreting gastric mucosa or to vagal hyperactivity, or both. 

---

Deficiency of Gastric Mucin in the Pathogenesis of Peptic Ulcer... 

Gastric ulceration induced by NSAIDs is a neutrophil-dependent process (78) and the association of H. pylori infection with neutrophil infiltration has also been well documented. Gastric injury by NSAIDs is minimal in neutropenic animals, and the cumulative incidence of peptic ulcers in long-term NSAID users is increased in the presence of neutrophil infiltration in the mucosa of patients who are H. py/on-positive, suggesting a possible link between NSAIDs and H. pylori in the pathogenesis of peptic ulcers (79,80). 

In summary, NSAIDs and H. pylori can cause adverse effects on gastroduodenal mucosal protective mechanisms in different ways, and so the interaction between these two susceptibility factors might allow damage to occur more readily when NSAIDs are taken in the presence of H. pylori infection. However, despite this experimental evidence, the interaction between H. pylori infection and use of NSAIDs in the pathogenesis of peptic ulcers and their complications is still unclear from clinical studies. 

Soil AH. Pathogenesis of peptic ulcer and implications for therapy. N Engl J Med 1990 322 909-16. 

The pathogenesis of peptic ulceration is not yet clear. It could be due to an imbalance between acid secretion and mucosal defensive and/or protective mechanisms, but the association between H. pylori and peptic ulceration has questioned this hypothesis. Therefore, drugs inhibiting acid secretion and/or eradicating H. pylori are of major interest. 

Figure 5-7. Boris Babkin s diagram of the innervation of the gastric mucosa showing his supposition that acetylcholine (AC), as the neurotransmitter of vagal impulses, liberates histamine (H). (Reprinted, by permission of the publisher, "The Abnormal Functioning of the Gastric Secretory Mechanism as a Possible Factor in the Pathogenesis of Peptic Ulcer," CAM/, Vol 38, May 1938.)...

Babkin BP. The abnormal functioning of the gastric secretory mechanism as a possible factor in the pathogenesis of peptic ulcer. Can Med Assoc J 38 421 -429, 1938. 

The pathogenesis of peptic ulcer may best be viewed as representing a complex scenario involving an imbalance between defensive and aggressive factors, of which the most notable now appears to be H. pylori. Although mucosal restitution and the reestablishment of epithelial cell continuity independent... 

The role of caffeine in the pathogenesis of peptic ulcer and gastrointestinal complaints remains unclear, and no association has been found in clinical and epidemiological studies. 

Circunstantial evidence directly implicating dopamine in the pathogenesis of duodenal ulcer in man is the unusual incidence of peptic ulcer disease in dopamine-deficient disorders. From purely descriptive clinical and epidemiologic studies we know that patients with Parkinson s disease, before the introduction of dopamine therapy, had an excess of ulcer disease (72). One report even comments on the curiosity that after initiation of L-DOPA administration the ulcer symptoms have virtually disappeared (72 ). On the other hand, less clearly, schizophrenia which is associated with dopamine excess and/or receptor hyperactivity is accompanied by virtual lack, or decreased prevalence, of peptic ulcer (73-76). Schizophrenia associated with ulcer disease has been viewed as a reportable curiosity in medical literature (75). At present, possibly because of the widespread therapeutic application of neuroleptics, the lack of peptic ulcer disease in schizophrenics is less striking than in the past. On the other hand, we recently observed in our autopsy series perforated duodenal ulcers in two schizophrenic patients who had been on large doses of haloperidol therapy (Szabo, unpublished observation). Thus, even in man, dopamine may indeed be implicated in the pathogenesis of duodenal ulcer disease. 

NSAlDs also are very frequently associated with peptic ulcers (in up to 60% of patients, particularly those with complications such as bleeding). Topical injury by the luminal presence of the dmg appears to play a minor role in the pathogenesis of these ulcers, as evidenced by the fact that ulcers can occur with very low doses of aspirin (10 mg) or with parenteral administration of NSAlDs. The effects of these drugs are instead mediated systemicaUy the critical element is suppression of COX-1 in the mucosa and decreased production of the cytoprotective prostaglandins PGE and PGI. ... 

Helicobacter pylori is associated with chronic gastritis, peptic ulceration and possibly involved in the pathogenesis of gastric carcinoma (Correa and Ruiz, 1992 Dixon,... 

III. Eradication of Helicobacter pylori C. This microorganism plays an important role in the pathogenesis of chronic gastritis and peptic ulcer disease. The combination of antibacterial drugs and omeprazole has proven effective. In case of intolerance to amoxicillin (p. 270) or clarithromycin (p. 276), metronidazole (p. 274) can be used as a substitute. Colloidal bismuth compounds are also effective however, the problem of heavy-metal exposure compromises their long-term use. 

Although the first documented case of perforated peptic ulcer disease dates back more than 2,000 years to the western Han dynasty, the problem continues to confound physicians. In many instances, the first indication of a peptic ulcer may be the perforation itself, whereas in others, previous vague symptomatology suddenly culminates in acute perforation with peritonitis. The pathogenesis of the situation whereby an indolent or even chronic disease suddenly converts... 

---