Pathophysiology

Peptic Ulcer Disease and Gastritis

Acid-peptic injury to the mucosa of the stomach and duodenum in the form of inflammation, erosion and ulcerations occurs infrequently in childhood. Gastroduodenal ulcers are classified as either primary or secondary (Tables 4.3). Primary ulcerations occur in the absence of any underlying systemic disease, acute medical illness, or ulcerogenic medications. Secondary ulcers are related to prematurity, steroid use, sepsis, or major physical or thermal injury. Children in need of surgical evaluation or therapy for these disorders often present with complications such as bleeding, perforation, obstruction, or chronicity.

Tables 4.3

Classification and Causes of Gastritis and Ulcers in Children

Basal acid output in children with peptic ulcer disease is not significantly different than that of control subjects. Although acid and pepsin are necessary for the develop­ment of ulcers, acid hypersecretion is only rarely the sole cause of peptic ulcer disease. The Zollinger-Ellison syndrome (hypergastrinemia secondary to gastrinoma) is excep­tionally rare in children. The increased frequency of peptic ulcer disease in children with chronic renal failure is attributed to elevated gastrin levels. G-cell hyperplasia, systemic mastocytosis and hyperparathyroidism are rare conditions associated with increased hyperacidity.

Peptic ulceration results from the interaction of hydrochloric acid, pepsin and the protective mucosal barrier. The most common mechanism for ulcer formation involves a decrease in the ability of the mucosa to generate the thick mucus layer on the surface of the stomach to provide an effective barrier to acid. Continuous cell turnover in the gastric mucosa assures epithelial integrity and cell regeneration after injury. Cholinergic agonists, prostaglandins and cytokines stimulate the release of mucus.

Mucosal ischemia reduces mucus production. Steroids, anti-inflammatory medications, or a low arterial pH of the blood supplying the stomach further impair the ability of the mucosa to protect itself. Inadequate gastric emptying may exacerbate mucosal injury by increasing the duration of exposure to acid.

Helicobacter pylori is a fastidious, urease producing, spiral-shaped, Gram-negative rod whose rediscovery has changed traditional concepts about the pathogenesis and treatment of peptic ulcer disease. The hydrolysis of urea to ammonia and water produces an alkaline microenvironment that shields the bacteria from gastric acid. Bacteria and their cytotoxins are responsible for the inflammatory process. H. pylori gastritis is the most common cause of chronic gastritis in children. Nearly all patients with duodenal ulcers and about 85% of patients with gastric ulcers are infected with H. pylori. However, there is little evidence to link H. pylori to gastric ulcer formation in children.

Primary Peptic Ulcer Disease

The true incidence of peptic ulcer disease in children is unknown. Although the incidence in boys is 2 to 3 times higher than that in girls, the sex distribution is similar in infants and very young children.

Ulcers occur more often in patients with blood type O, who have a 30% increased risk for developing duodenal ulcers when compared with those individuals with blood types A, B, and AB.

A strong familial tendency has been noted. 33–56% of children with ulcer disease have first- and second-degree relatives with peptic ulcer disease.

Recent advances in endoscopy have established a causal relationship between Helicobacter pylori and peptic ulcer disease in children. In developing countries, up to 70% of children are infected with H. pylori by 15 years of age. H. pylori transmission is person to person via fecal-oral, oral-oral, or gastro-oral routes. The gastro-oral route of transmission infers the vomitus as the contaminant in situations of overcrowding and poor sanitation.

Secondary Peptic Ulcer Disease

Secondary ulcers (stress ulcers) are acute ulcers in children usually associated with major physical or thermal trauma, sepsis, shock, or other critical illness.

Gastric stress ulcers are usually multiple superficial mucosal erosions found primarily in the fundus of the stomach. The cause of gastrointestinal ulcers has been related to one or a combination of three factors: (1) decreased mucosal blood flow, (2) disruption of the protective mucosal barrier, and (3) intraluminal acidity. Stress ulcers account for 80% of the peptic disease seen during infancy and early childhood.

Stress ulcers in children are duodenal, single, and deeply penetrating; in contrast, stress ulcers in adults are multiple and superficial.