What causes chronic gastritis and gastroduodenitis?

Causes of chronic gastritis and gastroduodenitis in children

Chronic gastroduodenitis and peptic ulcer disease in children are classified as polyetiological (multifactorial) diseases. However, in recent years, traditional ideas about the mechanisms of chronic gastritis and peptic ulcer disease have changed significantly. The discovery of Helicobacter pylori (HP) by B. Marshall in 1983 became the basis for revising previous ideas about the etiology and pathogenesis of stomach and duodenal diseases in children. Studies conducted in our country have established the fact of HP invasion in more than 80% of children with chronic diseases of the upper gastrointestinal tract. The incidence of HP increases with age: at 5-6 years it is 45%, by 12-14 years - 60-70%. Chronic gastritis, gastroduodenitis, peptic ulcer disease are pathogenetically associated with this infection. In the structure of chronic gastritis, 70% is gastritis associated with HP. In patients with peptic ulcer disease, HP is found in the mucous membrane of the antrum of the stomach in 90-100% of those examined, with superficial lesions of the gastroduodenal mucous membrane - in 36-81% of children. Duodenitis develops more often against the background of Helicobacter gastritis and metaplasia of the epithelium of the duodenum into the gastric (60-86%). The infection can spread through water sources; the microorganism remains viable in water for several days, and it can be cultivated from feces, saliva, plaque on the teeth of infected individuals. Transmission of infection from individual to individual occurs either by the feco-oral or oral-oral route. Bacterial colonization of the gastric mucosa is carried out by adhesion of microorganisms to epithelial cells through receptor interaction. Infection with HP results in the development of an inflammatory infiltrate in the mucous membrane, including the proper plate of the stomach, and metaplastic areas of the duodenal mucosa due to the destruction of its protective layer by enzymes produced by the microorganism. Numerous cases of HP carriage have been described in modern literature. However, prospective epidemiological studies conducted in various countries have shown that the colonization of HP and long-term persistence of infection on the gastric mucosa always causes qualitative changes on its part, leading to the development of atrophy, intestinal metaplasia and, as a consequence, to carcinogenesis. Thus, endoscopic signs of nodular gastritis, indirectly indicating the degree of inflammatory changes, were observed in 11% of children at the beginning of observation; they increased to 64% by the end of the first year and 80% by the end of the second year (mainly in boys) with a constant density of colonization of the body of the stomach and antrum. In addition, asymptomatic peptic ulcer disease was noted in 38% of parents of children suffering from inflammatory diseases of the upper gastrointestinal tract. It was established that the bacterium can persist in the human body until eradication therapy is carried out.

In addition to the infectious theory of the pathogenesis of gastroduodenitis, there are a number of endogenous etiological factors that affect the mucous membrane through neuroreflex and endocrine-humoral effects in case of disruption of the central nervous system, endocrine system, imbalance between the factors of aggression and protection of the organs of the gastroduodenal system.

[ 1 ], [ 2 ], [ 3 ], [ 4 ]

Endogenous factors

• Regulatory disorders of the central nervous system and its autonomic divisions (post-traumatic encephalopathy, hypothalamic syndrome, neurosis, neurotic conditions) lead to a disruption of the motor-evacuation function of the gastroduodenal division of the gastrointestinal tract.
• Endocrine diseases (diabetes mellitus, hypothyroidism, endemic goiter, Itsenko-Cushing syndrome, obesity, pathology of the adrenal glands and sex glands) increase the value of the acid-peptic factor: there is an increase in acid production in the stomach and an increase in the level of hormones that regulate motor function (secretin, cholecystokinin, motilin).
• The presence of duodenogastric reflux, as a result of which the damaging effect on the mucous membrane is exerted by pancreatic enzymes, bile acids, lysolicitin. This contributes to an increase in the level of histamine and thromboxane, and they in turn increase hyperemia and edema of the mucous membrane.
• Chronic diseases accompanied by the development of circulatory failure (cardiac and respiratory failure with tissue hypoxia) - the occurrence of microcirculatory disorders (areas of hyperemia, venous congestion, perivascular edema).
• Allergic and autoimmune diseases - vasculitis, localized in the vessels of the stomach and duodenum.
• Changes in the phagocytic link of immunity, disturbances in the ratio of T-lymphocyte subpopulations of cellular immunity.
• Operations on abdominal organs.

[ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ]

Exogenous factors

• Violation of the diet: irregular meals, significant intervals between meals, dry eating, overeating, large amounts of food that has a choleretic effect.
• Long-term use of medications (salicylates, glucocorticoids, non-steroidal anti-inflammatory drugs, cytostatics, pyrimidine drugs).
• Stressful situations - significant school and extracurricular workload, unfavorable family environment, conflicts with peers.
• Hypokinesia.
• Food allergy - increased effects of histamine, increased activity of the kallikrein-kinin system.
• Various intoxications - the presence of foci of chronic infections.
• Hereditary factors are also important - a polygenic type of inheritance with a large role of exogenous factors.

[ 10 ], [ 11 ], [ 12 ], [ 13 ]

Aggressive factors

Aggressive factors of the gastrointestinal-duodenal contents include hydrochloric acid, pepsin, pancreatic enzymes, bile acids, isolecithins, RNA infection, prolonged peptic proteolysis, and hypergastrinemia.

[ 14 ], [ 15 ], [ 16 ], [ 17 ]

Protective factors

Mucus formation, alkaline secretion, regeneration of the integumentary epithelium, properties of saliva, biotransformation processes (slowing down the metabolism of xenobiotics and endogenous compounds as a result of decreased activity of the liver monooxygenase system), antioxidant and immune homeostasis of the body.

Pathogenesis of gastroduodenitis and peptic ulcer in children

In the mechanism of development of morphological restructuring of the gastroduodenal mucosa, 2 factors are important. These are the effect of the infectious agent HP on the mucosa (80%) and toxic-allergic effects (endogenous and exogenous causes), leading to changes in the lymphoepithelial barrier of the gastroduodenal mucosa and a persistently high level of acid-peptic production in the stomach.

HP induces an inflammatory process in the stomach and increases the sensitivity of the gastroduodenal membrane to the effects of hydrochloric acid. Gastric metaplasia of the epithelium of the duodenal mucosa is a consequence of HP infection, it increases the risk of duodenal ulcer. Destruction of the protective layer of the gastroduodenal mucosa is a result of the action of bacterial enzymes. All HP strains produce a large amount of the enzyme urease, which hydrolyzes urea to carbon dioxide and ammonia, and the resulting concentration is sufficient to cause direct damage to epithelial cells up to the destruction of their membranes. Other enzymes secreted by HP - oxidase, catalase, superoxide dismutase - lead to the destruction of neutrophils, thereby preventing an adequate process of phagocytosis. More virulent HP strains produce cytotoxic protein Ca, which causes infiltration of the gastric mucosa by polymorphonuclear leukocytes. As a result of the HP antigen entering the epithelium, local and systemic immune response is stimulated: production of cytokines (TNF, IL-8, chemoattractants) promotes migration of neutrophils to the inflammation zone; the number of plasma cells producing secretory IgA increases, and production of IgG predominates, which promotes the development of erosive processes; antibody synthesis and production of toxic oxygen radicals occur - all this leads to constant local damage to the mucous membrane. A complex system of specific and non-specific factors of immune defense forms a state of organ tolerance (non-reactivity to antigen entry), which can implement the autoimmune mechanism of the inflammatory process. The involvement of the immune system in the development of inflammation is the morphological basis of gastroduodenitis: infiltration of the mucous membrane with plasma cells, lymphocytes, histiocytes with an increase in the number of macrophages, fibroblasts, eosinophils, lymphocytes (MEL), local disruption of vascular-tissue permeability. Dystrophic and subatrophic changes in the epithelium contribute to cellular immune regulation. In Helicobacter chronic gastritis, infiltration of the mucous membrane with granulocytes is more pronounced and dystrophic and necrotic changes in epithelial cells occur. In children, atrophic changes in the mucous membrane develop extremely rarely and only in adolescence. In chronic antral gastritis, erosive changes are noted in 27-30% of cases. Foveolar hyperplasia occurs at the edges of erosions and ulcers, which is classified as gastric polyps. It is characterized by elongated pits, the presence of high branched ridges. At present, it is considered a regeneration disorder. Intestinal metaplasia occurs in Helicobacter gastritis, when among the epithelial cells of the gastric type, areas of intestinal epithelium containing bordered enterocytes and goblet cells are determined. In areas of intestinal metaplasia, adhesion of HP does not occur.In chronic duodenitis, inflammatory changes are more often localized in the proximal part of the duodenum, in the area of the bulb (bulbitis): there is a decrease in the height of the epithelial cells of the villi, a decrease in the number of goblet cells; in the proper plate - infiltration by polymorphonuclear neutrophils, plasma cells, macrophages. The number of Paneth cells (at the bottom of the crypts), which have a trophic function aimed at the proliferating epithelium, decreases. During the healing of superficial erosions in the course of reparative regeneration, as a result of a violation of differentiation, gastric metaplasia of the epithelium occurs, which can be considered a manifestation of adaptation to acidic gastric contents, since the epithelial cells of the stomach resist the damaging effect of hydrochloric acid. In areas of gastric metaplasia, adhesion and colonization of HP is possible, which is considered a pre-ulcer condition in the mucous membrane of the duodenum. Thus, HP causes damage to the mucous membrane by direct interaction with laminin of the epithelial basement membrane, the effect of its enzymes, activation of cytotoxic T-lymphocytes by the HP antigen (lipopolysaccharide), increased production of gastrin, hydrochloric acid, histamine as a result of a decrease in the number of G-cells containing somatostatin mRNA, and hyperplasia of O-cells, with a change in the concentration of EOP and TOP. In phase I, NR eliminates the inhibitory effect of somatostatin and cholecystokinin - determines an increase in the concentration of gastrin. In phase 2, prolonged hypergastrinemia leads to hyperplasia of ECb cells (tissue basophils) with an increase in histamine production and subsequent persistent hyperchlorhydria - the direct cause of ulcer formation. Ammonia, a product of HP's vital activity, initiates apoptosis processes. Lipopolysaccharide (LPS) HP also participates in the stimulation of apoptosis. The latter increases the infiltration of the lamina propria by lymphocytes equipped with receptors for neurotransmitters that enhance the motor function of the stomach. This leads to the release of acidic gastric contents into the duodenum and to the development of gastric metaplasia. The cause of hypersecretion of hydrochloric acid is hyperplasia of parietal cells, the mass of O- and O-cells, which is genetically determined. But for the development of peptic ulcer disease, HP infection is necessary. Remission in patients lasts until HP reinfection occurs.which can be considered as a manifestation of adaptation to the acidic gastric contents, since the epithelial cells of the stomach resist the damaging effect of hydrochloric acid. In areas of gastric metaplasia, adhesion and colonization of HP is possible, which is considered a pre-ulcer condition in the duodenal mucosa. Thus, HP leads to damage to the mucous membrane by direct interaction with laminin of the basal membrane of the epithelium, the effect of its enzymes, activation of cytotoxic T-lymphocytes by the HP antigen (lipopolysaccharide), increased production of gastrin, hydrochloric acid, histamine as a result of a decrease in the number of G-cells containing somatostatin mRNA, and hyperplasia of O-cells, with a change in the concentration of EOR and TOP. In phase I, NR eliminates the inhibitory effect of somatostatin and cholecystokinin - determines an increase in the concentration of gastrin. In phase 2, prolonged hypergastrinemia leads to hyperplasia of ECb cells (tissue basophils) with increased histamine production and subsequent persistent hyperchlorhydria, the direct cause of ulcer formation. Ammonia, a product of HP activity, initiates apoptosis processes. HP lipopolysaccharide (LPS) also participates in the stimulation of apoptosis. The latter increases the infiltration of the lamina propria by lymphocytes equipped with receptors for neurotransmitters that enhance the motor function of the stomach. This leads to the release of acidic gastric contents into the duodenum and the development of gastric metaplasia. The cause of hydrochloric acid hypersecretion is hyperplasia of parietal cells, the mass of O- and O-cells, which is genetically determined. But HP infection is necessary for the development of peptic ulcer disease. Remission in patients lasts until HP reinfection occurs.which can be considered as a manifestation of adaptation to the acidic gastric contents, since the epithelial cells of the stomach resist the damaging effect of hydrochloric acid. In areas of gastric metaplasia, adhesion and colonization of HP is possible, which is considered a pre-ulcer condition in the duodenal mucosa. Thus, HP leads to damage to the mucous membrane by direct interaction with laminin of the basal membrane of the epithelium, the effect of its enzymes, activation of cytotoxic T-lymphocytes by the HP antigen (lipopolysaccharide), increased production of gastrin, hydrochloric acid, histamine as a result of a decrease in the number of G-cells containing somatostatin mRNA, and hyperplasia of O-cells, with a change in the concentration of EOR and TOP. In phase I, NR eliminates the inhibitory effect of somatostatin and cholecystokinin - determines an increase in the concentration of gastrin. In phase 2, prolonged hypergastrinemia leads to hyperplasia of ECb cells (tissue basophils) with increased histamine production and subsequent persistent hyperchlorhydria, the direct cause of ulcer formation. Ammonia, a product of HP activity, initiates apoptosis processes. HP lipopolysaccharide (LPS) also participates in the stimulation of apoptosis. The latter increases the infiltration of the lamina propria by lymphocytes equipped with receptors for neurotransmitters that enhance the motor function of the stomach. This leads to the release of acidic gastric contents into the duodenum and the development of gastric metaplasia. The cause of hydrochloric acid hypersecretion is hyperplasia of parietal cells, the mass of O- and O-cells, which is genetically determined. But HP infection is necessary for the development of peptic ulcer disease. Remission in patients lasts until HP reinfection occurs.supplied with receptors for neurotransmitters that enhance the motor function of the stomach. This leads to the release of acidic gastric contents into the duodenum and to the development of gastric metaplasia. The cause of hypersecretion of hydrochloric acid is hyperplasia of parietal cells, the mass of O- and O-cells, which is genetically determined. But for the development of peptic ulcer disease, HP infection is necessary. Remission in patients lasts until HP reinfection occurs.supplied with receptors for neurotransmitters that enhance the motor function of the stomach. This leads to the release of acidic gastric contents into the duodenum and to the development of gastric metaplasia. The cause of hypersecretion of hydrochloric acid is hyperplasia of parietal cells, the mass of O- and O-cells, which is genetically determined. But for the development of peptic ulcer disease, HP infection is necessary. Remission in patients lasts until HP reinfection occurs.

In non-Helicobacter gastroduodenitis, the infiltration of the lamina propria by lymphocytes is more pronounced, the number of interepithelial lymphocytes - T-lymphocytes (Th3 type) increases, in preschool children eosinophilic granulocytes (40%) appear, cells producing immunoglobulins of classes A, M, B and E (especially in case of food allergy), erosions are detected less often. Inflammatory changes in the gastroduodenal mucosa in these cases occur under the influence of exogenous, endogenous factors and imbalance of aggression and defense factors in case of neuroreflex, humoral and endocrine disorders. The probability of a decrease in the function of the protective barrier of the gastroduodenal mucosa increases with an increase in the number of risk factors, duration and intensity of their action, especially against the background of hereditary predisposition. Inflammation occurs: the reproduction of germinal elements and the maturation of mucosal cells are inhibited. The above primarily concerns the differentiation of the main and parietal cells, which die faster and lose their specific features: the ability to produce pepsin, hydrochloric acid, gastrointestinal hormones; areas (endoscopic picture) deprived of mucous coating appear - hemorrhagic, incomplete flat and complete tissue erosions, ulcers. The inflammatory process progresses in the presence of duodenogastric reflux: under the influence of duodenal contents (bile acids, their salts, lysolicitins, pancreatic enzymes), the protective barrier of gastric mucus is damaged (reverse diffusion of hydrogen ions, increase in transmembrane sodium flow) by destroying biological membranes, releasing lysosomal enzymes. This leads to cytolysis of the surface epithelium and maintains the inflammatory reaction. Under conditions of low gastric secretion, pancreatic enzymes cause an increase in the level of histamine and thromboxane, which, by acting on the H1 and H2 receptors of blood vessels, cause swelling of the mucous membrane, disruption of microcirculatory processes with loss of plasma proteins, an increase in the level of prostaglandins, which leads to the development of hemorrhages and erosions of the mucous membrane. Increased vascular permeability, changes in the rheological properties of the blood, and an increase in the activity of the kallikrein-kinin system of the blood enhance these processes. Thus, the epithelium loses its characteristic morphometric and functional features due to the displacement of differentiated cells by younger and immature forms. Progression of the process can lead to the prevalence of death of glandular elements over their neoplasm, the development of subatrophy and atrophy and restructuring of the glandular apparatus with subsequent secretory insufficiency.

Pathogenesis of gastroduodenitis

Genetic factors: hyperplasia of B- and deficiency of O-cells cause hypergastrinemia and hypersecretion of HCl.

• Influence of HP.
• Adhesion - microdefects of the mucous membrane, lymphoid infiltrate.
• Infiltration of lymphocytes with receptors for neurotransmitters - increased motor function, development of gastric metaplasia - duodenitis, ulceration, regeneration.
• Under the influence of LPS - NR activation of cellular immune reactions, where mainly T-lymphocytes are involved (IL-2, -4, -5, FIO).
• NR-phenotype with CagA+ and VaсA+ - cytolytic activity - ulcerative defect.
• YR-urease is a chemotactic factor (monocytes, leukocytes) - damage to the epithelium.
• Urease is the hydrolysis of urea in gastric juice into ammonium ions, destroying the epithelium.
• HP-catalase and superoxide dismutase - inhibition of phagocytosis, stimulation of apoptosis, activation of leukocyte metabolites. As a result - damage to small vessels, disruption of microcirculation and trophism, CO-thrombi - focal infarctions of the gastric mucosa - ulcers.
• HP reduces the number of D-cells, enhances the work of G-cells, resulting in the elimination of the inhibitory effect of somatostatin, an increase in the concentration of gastrin and histamine, hypergastrinemia. Violation of cellular differentiation, reorganization of the glandular apparatus, motor, evacuation, secretory insufficiency - disruption of digestion processes.