What causes chronic gastritis and gastroduodenitis?

Causes of chronic gastritis and gastroduodenitis in children

Chronic gastroduodenitis and peptic ulcer in children are referred to polyethological (multifactorial) diseases. However, in recent years, the traditional ideas about the mechanisms of the formation of chronic gastritis and peptic ulcer have changed significantly. The discovery in 1983 of V. Marshall Helicobacter pylori (HP) became the basis for revising previous concepts of the etiology and pathogenesis of diseases of the stomach and duodenum 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 digestive 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 are pathogenetically associated with this infection. In the structure of chronic gastritis, 70% is associated with gastritis associated with HP. In patients with peptic ulcer HP is detected in the mucosa of the antral part of the stomach in 90-100% of the subjects, with superficial lesions of the gastroduodenal mucosa - in 36-81% of children. Duodenitis develops more often against a background of helical bacterial gastritis and metaplasia of the epithelium of the duodenum in the gastric (60-86%). Infection can spread through water supply sources; the microorganism retains vital activity in water for several days, and it can be cultivated from feces, saliva, and plaque on the teeth of infected individuals. Transmission of infection from an individual to an individual occurs either fecal-oral, or oral-oral. Bacterial colonization of the gastric mucosa is accomplished by adhesion of microorganisms to epithelial cells through receptor interaction. Infection with HP leads to an inflammatory infiltrate in the mucosa, including its own plate of the stomach, and metaplastic sites of the duodenal mucosa due to the destruction of its protective layer by the microorganism-produced enzymes. In the modern literature, numerous cases of HP carriage are described. However, prospective epidemiological studies conducted in various countries have shown that HP colonization and long persistence of infection on the gastric mucosa always causes qualitative changes on its part leading to the development of atrophy, intestinal metaplasia and, consequently, carcinogenesis. So, endoscopic signs of nodular gastritis, indirectly indicating the degree of inflammatory changes, were observed in 11% of children at the beginning of the 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 is established that the bacterium can persist in the human body until eradication therapy is performed.

In addition to the infectious theory of the pathogenesis of gastroduodenitis, there are a number of endogenous etiological factors that affect the mucosa through neuro-reflex and endocrine-humoral effects when the CNS, endocrine system is disrupted, and the imbalance between aggression factors and the protection of the gastroduodenal system.

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

Endogenous factors

• Regulatory disorders of the central nervous system and its vegetative divisions (posttraumatic encephalopathy, hypothalamic syndrome, neurosis, neurotic states) lead to disruption of the motor and evacuation function of the gastroduodenal GIT.
• Endocrine diseases (diabetes mellitus, hypothyroidism, endemic goiter, Itzenko-Cushing syndrome, obesity, adrenal gland pathology and sexual glands) increase the importance of the acid-peptic factor: acid production in the stomach increases and the level of hormones regulating motor function (secretin, cholecystokinin, motilin).
• The presence of duodenogastric reflux, resulting in a damaging effect on the mucosa has pancreatic enzymes, bile acids, lysolycine. This helps to increase the level of histamine and thromboxane, and they in turn increase hyperemia and edema of the mucosa.
• Chronic diseases, accompanied by the development of circulatory failure (cardiac and respiratory failure with tissue hypoxia), - the emergence of microcirculatory disorders (areas of hyperemia, venous stasis, 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 cell subpopulations of cellular immunity.
• Surgery on the organs of the abdominal cavity.

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

Exogenous factors

• Disruption of diet: irregular intake of food, significant intervals between meals, dryness, overeating, large amounts of food with a sodic effect.
• Long-term use of medications (salicylates, glucocorticoids, non-steroidal anti-inflammatory drugs, cytotoxic drugs, pyrimidine drugs).
• Stressful situations - significant school and extra-school activities, unfavorable family environment, conflicts with peers.
• Hypokinesia.
• Food allergy - increased exposure to histamine, increased activity of kallikrein-kinin system.
• Various intoxications - the presence of foci of chronic infections.
• Attached importance also to hereditary factors - the polygenic type of inheritance with the great role of exogenous factors.

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

Aggressive factors

The aggressive factors of gastro-duodenal contents include hydrochloric acid, pepsin, pancreatic enzymes, bile acids, isoleucinates, NR infection, prolonged peptic proteolysis, hypergastrinemia.

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

Protection Factors

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

Pathogenesis of gastroduodenitis and peptic ulcer disease in children

In the mechanism of the development of morphological restructuring of the gastro-duodenal mucosa there are 2 factors. This effect on the mucosa of the infectious agent HP (80%) and the toxic-allergic effect (endogenous and exogenous causes), leading to changes in the lymphoepithelial barrier gastroduodenal mucosa and resistant to high levels of acid-peptic production in the stomach.

HP induces an inflammatory process in the stomach and increases the sensitivity of the gastroduodenal membrane to hydrochloric acid. Gastric metaplasia of the epithelium of the duodenal mucosa is a consequence of HP infection, it increases the risk of duodenal ulcers. The destruction of the protective layer of the gastroduodenal mucosa is the result of the action of bacterial enzymes. All HP strains produce a large amount of urease enzyme that hydrolyzes urea to carbon dioxide and ammonia, and the concentration obtained is sufficient to cause direct damage to epithelial cells until the destruction of their membranes. Other enzymes released by HP - oxidase, catalase, superoxide dismutase - lead to the destruction of neutrophils, thereby inhibiting the adequate process of phagocytosis. More virulent strains of HP produce a cytotoxic Ca protein that causes infiltration of the gastric mucosa by polymorphonuclear leukocytes. As a result of the arrival of the HP antigen under the epithelium, the local and systemic immune response stimulates: the production of cytokines (TNF, IL-8, chemoattractants) promotes the migration of neutrophils to the inflammation zone; the number of plasma cells producing secretory IgA increases, and IgG production is also prevalent, which contributes to the development of erosive processes; there is a synthesis of antibodies and the production of toxic oxygen radicals - all this leads to permanent local damage to the mucous membrane. A complex system of specific and nonspecific immune defense factors forms a state of organ tolerance (the reactivity to antigen supply), which can realize the autoimmune mechanism of the inflammatory process. The involvement of the immune system in the development of inflammation constitutes 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. Cellular immune regulation is facilitated by dystrophic and subatrophic changes in the epithelium. In Helicobacter chronic gastritis, infiltration of the mucous membrane with granulocytes is more pronounced and dystrophic and necrotic changes of epithelial cells occur. At children, atrophic changes in the mucous membrane develop extremely rarely and only in adolescence. With chronic antral gastritis, erosive changes are noted in 27-30% of cases. In the edges of erosions and ulcers arises foveolar hyperplasia, which is referred to the polyps of the stomach. It is characterized by elongation of the pits, the presence of high branched ridges. Currently, it is considered a violation of regeneration. When helikobakternom gastritis occurs intestinal metaplasia, when among the epitheliocytes of the gastric type determine the areas of the intestinal epithelium, containing granular enterocytes and goblet cells. In areas of intestinal metaplasia, there is no adhesion of HP. In chronic duodenitis, inflammatory changes are more often localized in the proximal part of the duodenum, in the bulbous area: a decrease in the height of the villous epitheliocytes occurs, the number of goblet cells decreases; in its own plate - infiltration of polymorphonuclear neutrophils, plasmocytes, macrophages. The number of Panet cells decreases (at the bottom of the crypt), which have a trophic function directed to the proliferating epithelium. With the healing of superficial erosions during reparative regeneration, gastric metaplasia of the epithelium arises as a result of impaired differentiation, which can be considered as a manifestation of adaptation to acidic gastric contents, as the gastric epitheliocytes counteract the damaging effect of hydrochloric acid. In areas of gastric metaplasia, adhesion and colonization of HP is possible, which is considered a pre-ulcer state in the duodenal mucosa. Thus, HP leads to damage to the mucous membrane by direct interaction with the laminin of the epithelium basement membrane, the action of its enzymes, activation of cytotoxic T-lymphocytes by antigen HP (lipopolysaccharide), increased production of gastrin, hydrochloric acid, histamine as a result of a decrease in the number of G cells containing somatostatin mRNA, and O-cell hyperplasia, with a change in the concentration of EOR and TOP. In phase I, the NR eliminates the inhibitory effect of somatostatin and cholecystokinin - it determines the increase in the concentration of gastrin. In the 2 nd phase, prolonged hypergastrinemia leads to hyperplasia of ECL cells (tissue basophils) with an increase in histamine production and subsequent persistent hyperchlorhydria, the direct cause of ulcer formation. Ammonia - the product of vital activity of HP - initiates the processes of apoptosis. Lipopolysaccharide (LPS) HP also participates in the stimulation of apoptosis. The latter increases the infiltration of the lamina propria with lymphocytes provided 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 reason for hypersecretion of hydrochloric acid is hyperplasia of parietal cells, mass of O- and O-cells, which is caused genetically. But for the development of peptic ulcer, HP infection is necessary. Remission in patients lasts until there is no reinfection of HP.

With non-gelikobakternom gastroduodenitis, the infiltration of the progenitor plate with lymphocytes is more pronounced, the number of interepithelial lymphocytes is increased by T lymphocytes (Th3 type), eosinophilic granulocytes (40%), cells producing immunoglobulins of classes A, M, B and E appear in preschool children (especially with food allergies), they rarely detect erosion. Inflammatory changes of the gastroduodenal mucosa in these cases occur when exposed to exogenous, endogenous factors and an imbalance of aggression and defense factors in neuro-reflex, humoral and endocrine disorders. The probability of reducing the function of the protective barrier of the gastroduodenal mucosa is enhanced with an increase in the number of risk factors, duration and intensity of their action, especially against a background of hereditary predisposition. There is inflammation: inhibition of reproduction of germ cells and maturation of cells of the mucosa. The abovementioned first of all concerns the differentiation of the main and parietal cells, which quickly die and lose their specific characteristics: the ability to produce pepsin, hydrochloric acid, gastrointestinal hormones; there are sites (endoscopic picture), devoid of mucous coatings, - hemorrhagic, incomplete flat and full tissue erosion, ulcers. The inflammatory process progresses in the presence of duodenogastric reflux: under the action of duodenal contents (bile acids, their salts, lysolycetins, pancreatic enzymes), the protective barrier of gastric mucus (reverse diffusion of hydrogen ions, build-up of transmembrane sodium flow) is damaged by destruction of biological membranes, lysosomal enzymes. This leads to cytolysis of the superficial epithelium and supports the inflammatory response. In conditions of low gastric secretion, pancreatic enzymes cause an increase in the level of histamine, thromboxane, which, acting on the H1, H2 receptors of the blood vessels, causes mucosal edema, disturbance of microcirculatory processes with loss of plasma proteins, increased levels of prostaglandins, leading to hemorrhagia and erosion mucous membrane. An increase in vascular permeability, a change in the rheological properties of the blood, an increase in the activity of the kallikrein-kinin system of blood strengthens these processes. Thus, the epithelium loses its characteristic morphometric and functional signs due to the displacement of differentiated cells by younger and immature forms. Progression of the process can lead to the predominance of death of glandular elements over their neoplasm, the development of subatrophy and atrophy, and the restructuring of the glandular apparatus with subsequent secretory insufficiency.

Pathogenesis of gastroduodenitis

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

• Influence of HP.
• Adhesion - microdefects of the mucosa, lymphoid infiltration.
• Infiltration of lymphocytes with receptors for neurotransmitters - strengthening of motor function, development of gastric metaplasia - duodenitis, ulceration, regeneration.
• Under the influence of LPS - NR-activation of cellular immune reactions, where mainly T-lymphocytes (IL-2, -4, -5, FIO) are involved.
• NR phenotype with CAGA + and VACA + - cytolytic activity - ulcerative defect.
• NR-urease - a factor of chemotaxis (monocytes, leukocytes) - damage to the epithelium.
• Urease - hydrolysis of urea of gastric juice into ammonium ions, destruction of the epithelium.
• HP-catalase and superoxide dismutase - inhibition of phagocytosis, stimulation of apoptosis, activation of leukocyte metabolites. As a result - damage to small vessels, a violation of microcirculation and trophism, CO thrombi - focal heart attacks of gastric cancer - 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, and hypergastrinemia. Disturbance of cellular differentiation, reorganization of glandular apparatus, motor, evacuation, secretory insufficiency - violation of digestion processes.