Causes and pathogenesis of gastric ulcer

Many theories of the development of peptic ulcer (inflammatory-gastritic, cortico-visceral, neuro-reflex, psychosomatic, acido-preventive, infectious, hormonal, vascular, immunological, traumatic) have been proposed, but none of them contain completely changes realized as a ulcerative mucosal defect the shell of the stomach and duodenum. In connection with this, peptic ulcer is considered a polyethological disease with heterogeneity of genetic predisposing factors.

There are a number of the most important etiological factors in the development of peptic ulcer disease:

• hereditary-genetic;
• neuropsychiatric (psychotrauma, persistent stress, including family conflicts);
• neuroendocrine;
• alimentary;
• infectious;
• immune.

To factors predisposing to the development of peptic ulcer in children are the following:

1. infection with Helicobacter pylori. In children with peptic ulcer Helicobacter pylori in the mucosa of the antrum of the stomach in 99% and in the mucosa of the duodenum in 96% of cases;
2. early transfer to artificial feeding, in which an increase in G (gastrin-producing) and H (histamine-producing) cells of the mucous membrane of the antrum of the stomach is induced;
3. alimentary errors;
4. long-term use of certain medicines (salicylates, glucocorticoids, cytostatics, etc.);
5. peculiarities of the family way of life - organization of life and upbringing of children, family features of nutrition, family relationships;
6. hypodynamia or physical overload;
7. foci of chronic infection;
8. intestinal parasitosis;
9. neuropsychic overload;
10. smoking and substance abuse;
11. food allergy.

Genetic predisposition to peptic ulcer is realized by increasing the synthesis of hydrochloric acid in the stomach (genetically determined increase in the weight of the lining cells and hyperactivity of the secretory apparatus), increasing the content of gastrin and pepsinogen (increased serum pepsinogen I, inherited in autosomal dominant type and found in 50% of patients peptic ulcer). Patients with peptic ulcer are diagnosed with a defect in the formation of mucus in the inner shell of the stomach and duodenum, expressed by a deficiency of mucopolysaccharides, including fucoglycoproteins, syndrochondroitin sulfates and glucosaminoglycans.

A certain effect on the formation of a ulcerative defect has a violation of the upper GI tract motility in the form of stagnation of acidic contents or acceleration of evacuation from the stomach into the duodenum without adequate alkalization of the acid.

As a result of examination of the genetic status of patients with peptic ulcer on 15 phenotypic polymorphism systems, duodenal ulcer was more often developed in 0 (1) blood group, Rh-negative and Gml (-) phenotypes. In contrast, blood group B (III), Rh-positive, Lewis ab- and the Gml (+) phenotype usually do not suffer from duodenal ulcer. An important factor in the genetic determinants of peptic ulcer disease is a violation of the blood supply to the gastric mucosa (mainly of small curvature) and the bulb of the duodenum.

Clinical and genealogical analysis of pedigrees of children with peptic ulcer of duodenum showed that the hereditary predisposition to the pathology of the digestive tract was 83.5%. Including more than half of the children had a hereditary burden of peptic ulcer and duodenal ulcer.

An important role in the development of peptic ulcer is played by neuropsychic disorders that affect the function of the immune system. The influence of the stress factor was found in 65% helicobacter-positive and in 78% of helicobacter-negative children with peptic ulcer.

Neuroendocrine factors are realized through the mechanisms of the APUD-system (gastrin bombesin, somatostatin, secretin, cholecisgokinin, motilin, enkephalins, acetylcholine). Gastrin is an intestinal hormone produced by G-cells of the stomach under the action of acetylcholine (characterizes the action of the vagus nerve), products of partial hydrolysis of food proteins, a specific "gastrin-releasing peptide" (bombesin) and gastric dilatation. Gastrin stimulates gastric secretion (exceeds histamine 500-1500 times), promotes hyperplasia of the underlying glands of the stomach, has ulceroprotective effect. Hyperproduction of gastrin or histamine can be a sign of Zollinger-Ellison syndrome, mastocytosis.

Acetylcholine also serves as an inducer of increasing the production of histamine by ECL-cells (Entero-chromaffine-Hke cell), which leads to hypersecretion and hyperacidity of the gastric juice and a decrease in the resistance of the gastric mucosa to acid-assisted aggression.

Somatostatin inhibits gastric secretion by suppressing G-cell production of gastrin, increasing the volume of bicarbonate production by the pancreas in response to a decrease in pH in the duodenum.

There is a study of the role of melatonin in the development and progress of the ulcerative process. Melatonin is the hormone of the pineal gland (pineal body), also synthesized by enterochromaffin cells (EC cells) of the gastrointestinal tract. The participation of melatonin in the regulation of body biorhythms, antioxidant and immunomodulating effects, the influence on gastrointestinal motility, microcirculation and proliferation of the mucous membrane, the ability to inhibit acid formation are proved. Melatonin affects the organs of the digestive tract both directly (by interacting with its own receptors), and by binding and blockade of receptors gastrin.

In the pathogenesis involved not only increased secretion of intestinal hormones, but also the genetically caused hypersensitivity of the lining cells to gastrin, histamine.

Alimentary factors are realized in violation of diet: irregular diet, consumption of fried, smoked food, use of products with high salt content, extractives, preservatives, flavor enhancers.

The main factor of chronic ulcerogenesis is inflammation of the mucosa of the gastroduodenal zone, caused and maintained by H. Pylori. Regularly publish data that peptic ulcer refers to gastritis-associated diseases. H. Pylori is in contact with cytokines released by various cells of the epithelium of the mucous membrane, primarily with interleukin 8, which changes the parameters of chemotaxis, chemokinesis, aggregation and release of lysosomal enzymes from neutrophils. The occurrence or relapse of peptic ulcer disease can be caused by the continued impact of altered signaling systems triggered by H. Pylori, even if the causative agent has undergone eradication.

The pathogenesis of duodenal ulcer is still poorly understood. The concept of a shift in the balance between aggressive and protective factors is relevant, which causes damage to the mucous membrane. Aggressive include acid-peptic factor and pyloric helicobacteriosis, and to protective mucus of the stomach and duodenum (glycoproteins, bicarbonates, immunoglobulins, etc.), high reparative activity of the mucosa under condition of adequate blood supply.

Most researchers agree that individual differences in the components of natural resistance can neutralize or reduce the "aggressiveness" of a particular risk factor (genetic predisposition, imbalance between the factors of aggression or protection), as well as inactivate the effect of triggers that are not incapable of leading to the development of ulcerative disease.

The significant role of vegetative imbalance in the development of peptic ulcer (provocation of changes in homeostasis, increased intensity of local factors of aggression and a decrease in the protective properties of the mucous barrier, hyperhemocoagulation, decreased immunological resistance and activation of local microflora, motor disturbance) is proved.

Residual organic background and / or psycho-traumatic situations (depression) through an increase in the tone of the parasympathetic nervous system lead to gastric hypersecretion and the formation of a ulcerative defect in the duodenum. In turn, a prolonged course of duodenal ulcer contributes to the formation of psychoemotional disorders, including depression, the progression of vegetative disorders in the serotonin system, aggravating the course of the pathological process. Both vagotonia (through stimulation of gastric secretion) and sympathicotonia (disturbance of microcirculation in the organ wall) contribute to ulcer formation.

Congenital hyperplasia of gastrin producing G cells of the antral part of the stomach and duodenum promotes hypergastrinemia and gastric hypersecretion, followed by the formation of a ulcerative defect in the duodenum.

Colonization of H. Pylori antral stomach in a patient with hypersensitivity leads to the development of G-cell hyperplasia, gastric hypersecretion, gastric metaplasia in the duodenum and the formation of a ulcerative defect. The possibility and consequences of colonization of H. Pylori mucous membrane of the stomach and duodenum depend on the characteristics of the macroorganism, including the state of the immune system, features of the H. Pylori strain (pathogenicity factors).

The influence of immune factors on the development of peptic ulcer is caused both by defects in the immune reactivity of the organism (hereditary or acquired), and by the influence of H. Pylori pathogenicity factors, a violation of the biocenosis of the upper gastrointestinal tract.

Studies of the immune system in children with duodenal ulcer associated with H. Pylori infection have demonstrated immune status disorders due to imbalance in the cytokine system (interleukins 1, 4, 6, 8, 10 and 12, transforming growth factor-beta, interferon -y), an increase in IgG-class antibodies to tissue and bacterial antigens, an increase in the production of neutrophils of active forms by an oxygen-oxygen disease of the duodenum. The antibodies of IgG class found in children with tissue structures of the body (elastin, collagen, denatured DNA) and antigens of the gastrointestinal tract (stomach, small and large intestine, pancreas) can be considered a sign of autoimmune genesis of exacerbation of the disease. The production of autoantibodies to gastric tissues in H. Pylori infection is also proven in adults. The increase in the production of active forms of oxygen by neutrophils in children with peptic ulcer of the duodenum testifies to the participation of toxic substances secreted by neutrophils in the destructive process.

[1], [2], [3], [4], [5], [6], [7], [8]