Chapter 4 Perforated peptic ulcer

The frequency of peptic ulcer disease is estimated 6% to 15% in the general population. Most individuals do not have clinically significant ulcer. Approximately 10% of young men have H pylori, and the proportion of people with the infection increases steadily with age. The incidence of duodenal ulcer has been decreasing over the past 3–4 decades.

Lifetime prevalence of perforation in patients with peptic ulcer disease is approximately 5%. With nonsteroidal anti-inflammatory drugs (NSAID)-related ulcers, the incidence of perforation is 0.3%. Emergency operations for peptic ulcer perforation carry a mortality risk of 6–30%. Most deaths result from postoperative complications.

Aetiology

1. Predisposing factor: progressive destruction of stomach or duodenal wall.

Ulcers of the stomach and duodenum are caused chiefly by the effects of hydrochloric acid, produced by the parietal cells of the stomach, and by lack of protection of the mucosa against this acid. Acid production is the most important factor as far as duodenal ulcer is concerned, but cannot be the only factor, since the severity of duodenal ulcers and their responses to therapy do not vary directly with the amount of gastric acid secreted.

Additional factors are important in the production of gastric ulcers. Gastric contents can be retained for a much longer period than duodenal contents and are not neutralized rapidly. The mucous membrane of the stomach must normally be protected continuously from the damaging effect of the hydrochloric acid which it secretes. This protective layer consists of an adherent layer of mucus which is separated from the gastric mucosa by a bicarbonate layer that normally neutralizes any hydrochloric acid diffusing back through the mucous layer. The mucous layer also protects the gastric mucosa against other noxious agents such as bile, alcohol, and aspirin and other irritating drugs.

Secretion of acid by the parietal cells of the stomach is influenced by several mechanisms. Stimulation by the vagus nerves accounts for about 50% of acid secretion. Gastrin that is secreted by the antral mucosa causes 40 to 45% of the secretion and the remaining 5 to 10% is due to gastrin that comes from the intestinal tract from various APUD cells.

Production of gastric mucus should presumably vary according to the blood supply of the organ. Experimental studies have shown that prostaglandins increase the mucosal blood supply and increase the bicarbonate level and thickness of the mucous layer; they may, therefore, play an important role in the protection of the gastric mucosa.

Causes of gastric ulcers vary in importance depending upon the location of these ulcers. In 1965 Johnson observed the different behavior of ulcers in different portions of the stomach and classified them into three groups. In patients with type 1 ulcers, located in the body of the stomach, gastric acid secretion as determined by secretory tests is low. Here inadequate mucosal protection and back-diffusion of hydrochloric acid through the protective bicarbonate and mucous layer into the gastric mucosa seem to be involved in the disease. Silent suggested it is in this location that alternating waves of gastric acid from above and refluxing alkaline secretions from the duodenum destroy the protective layer of mucus.

Johnson’s type 2 gastric ulcers (those combined with a present or past duodenal ulcer) and type 3 (those in the prepyloric region) behave more like duodenal ulcers; here the effects of acid production appear to be more important.

A peptic ulcer occurs when an alteration occurs in the aggressive and/or protective factors such that the balance is in favor of gastric acid and pepsin. Any process that increases gastric acidity (e.g., individuals with increased maximal and basal acid output), decreases prostaglandin production (e.g., NSAIDs), or interferes with the mucous layer (e.g., Helicobacter pylori infection) can cause such an imbalance and lead to peptic ulcer disease.

H pylori infection that follows an antral predominant pattern leads to an inflammatory state in which high levels of tumor necrosis factor-alpha (TNF-alpha) and other cytokines are produced. These stimulate gastric acid production directly by increasing gastrin release from G cells and inhibit somatostatin production by antral D cells. This leads to a net increase in gastric acid secretion, which leads to an increased acid load in the duodenum, overwhelming the mucosal defense.

H pylori can then colonize the duodenal mucosa and adhere to cells. This adherence leads to a variety of second-messenger signals, which invoke an immunologic response against those cells causing mucosal damage by host neutrophils and other inflammatory cells.

H. pylori also affect the gastric and duodenal mucous layer because this organism produces proteases that degrade the protective mucous layer.

Moreover, H pylori infection decreases the production of epidermal growth factor, which normally promotes healing of gastric and duodenal mucosa.

H pylori organisms produce urease. Urease hydrolyzes urea to ammonia end carbon dioxide. Hydroxide ions produced by equilibration of ammonia with water may damage the gastric and duodenal mucosa.

2. Causative factor: increasing of pressure in stomach lumen (more food intake, physical training).