Etiology and Morphological Diagnostics
In addition to the primary factor—Helicobacter pylori (HP) infection—the etiology of chronic gastritis can involve nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, duodenogastric reflux, and autoimmune processes.
A direct correlation between the degree of mucosal colonization by HP and the severity of inflammation was first established by Australian pathologist J. Warren (who, along with B. Marshall, was awarded the Nobel Prize in 2005). For morphological diagnosis, the microorganism is visualized in the supraepithelial mucus layer using 0.1% toluidine blue staining.
Pathogenicity Factors: CagA and VacA
The pathogenicity of HP is largely determined by strain-specific biological features and host genetics. Two factors play a pivotal role:
- CagA protein. Upon phosphorylation, it activates the eukaryotic phosphatase SHP-2, triggering an intracellular cascade that leads to hyperproliferation (an effect resembling growth factor hyperstimulation). Absolute complementarity of the enzyme to tyrosine residues in CagA is required for activation. Their arrangement varies in "Western" strains, whereas it is strictly determined in "Asian" strains. This provides high affinity for SHP-2 and explains the increased incidence of gastric cancer in Asian countries.
- VacA gene. Present in all strains, it encodes the vacuolating cytotoxin. It forms pores in epithelial cell membranes through which anions and urea escape. The bacterium hydrolyzes urea, creating a protective ammonia "cloud" around itself. This neutralizes hydrochloric acid, allowing the microbe to survive. VacA also weakens lateral intercellular junctions.
Cytokine Dysregulation of Secretion
The infection provokes a robust immune response that disrupts the neuroendocrine regulation of the stomach via cytokine pathways:
- In the antrum: Th1 and Th2 lymphocyte cytokines (IFN-γ, IL-4) suppress D cells, reducing somatostatin production. Without its inhibitory influence, and under the direct stimulatory action of IL-8, TNF-α, and IFN-γ, G cells hypersecrete gastrin (leading to hypergastrinemia).
- In the gastric body: A paradoxical situation is observed—despite high gastrin levels, acidity drops. Inflammatory mediators (TNF-α, IL-1β) directly block parietal cell function (reducing HCl production) and ECL cells (decreasing histamine production, which normally stimulates acid secretion).
Evolution of Gastritis: Two Phenotypes
The outcome of the disease depends on the age of infection and the localization of the bacterium. Two main pathways of pathological development are distinguished:
- Ulcer phenotype (antral gastritis). The bacterium colonizes its natural niche, the antrum. A Th1-polarized response leads to hypergastrinemia and intensive hydrochloric acid production. Gastric juice aggressiveness increases, leading to a high risk of ulcer formation.
- Cancer phenotype (pangastritis). Seeking an optimal pH gradient, the bacterium migrates to the gastric body (often occurring with infection at an early age, around 3–5 years). Pangastritis with hypochlorhydria develops. By the 3rd to 4th decade of life, chronic inflammation leads to mucosal atrophy, hyposecretion, and the development of intestinal-type gastric cancer (occurring in 1–2% of patients).