Etiology and morphological diagnostics
In addition to the primary factor — Helicobacter pylori (HP) infection — the etiology of chronic gastritis may involve the use of nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, duodenogastric reflux, and autoimmune processes.
The direct correlation between the degree of mucosal colonization by HP and the severity of inflammation was first established by Australian pathologist J. Warren (for which he was awarded the Nobel Prize in 2005 alongside B. Marshall). For morphological diagnostics, the microorganism is visualized in the supraepithelial mucus using 0.1% toluidine blue staining.
Pathogenicity factors: CagA and VacA
The pathogenicity of HP is largely determined by the biological characteristics of the strains and host genetics. Two factors play a key 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). Activation requires absolute complementarity of the enzyme to the tyrosine residues in CagA. In "Western" strains, their location varies, whereas in "Asian" strains, it is strictly determined. This ensures high affinity for SHP-2 and explains the increased incidence of gastric cancer in Asian countries.
- VacA gene. Present in all strains and 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 contacts.
Cytokine dysregulation of secretion
The infection induces a potent immune response that disrupts the neuroendocrine regulation of the stomach via the cytokine system:
- In the antrum: Th1 and Th2 lymphocyte cytokines (IFN-γ, IL-4) suppress D cells, reducing somatostatin production. Without its inhibitory effect, and under the direct stimulatory action of IL-8, TNF-α, and IFN-γ, G cells begin to hypersecrete gastrin (hypergastrinemia ensues).
- In the gastric body: A paradoxical situation is observed — despite high gastrin levels, acidity drops. Inflammatory mediators (TNF-α, IL-1β) directly block the function of parietal cells (reducing HCl production) and ECL cells (reducing the production of histamine, 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 bacteria. Two main pathways of pathology development are distinguished:
- Ulcer phenotype (antral gastritis). The bacterium colonizes its natural niche — the antrum. A Th1-polarized response leads to hypergastrinemia and intense hydrochloric acid production. The aggressiveness of gastric juice increases, leading to a high risk of ulcer formation.
- Cancer phenotype (pangastritis). Seeking the optimal pH gradient, the bacterium migrates to the gastric body (often when infected at an early age, at 3–5 years). Pangastritis with hypochlorhydria develops. By the 3rd–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).
Briefly: answers to topical questions
What stages does the Correa cascade include in the pathogenesis of gastric cancer?
The Pelayo Correa cascade, describing the development of intestinal-type gastric cancer, includes sequential stages of mutations and phenotypic changes.
- Onset of mutations — occurs at the level of impaired cellular renewal.
- Phenotypic manifestation — development of intestinal metaplasia.
- Adenoma stage — characterized by a mutation of the p53 gene and accompanied by a decrease in allele heterozygosity (p53LOH).
- Outcome — emergence of invasive intestinal-type cancer.
What microscopic signs are characteristic of chronic atrophic gastritis?
Microscopic signs of chronic atrophic gastritis are assessed using the modified Sydney system and include:
- Degree of inflammation — lymphoplasmacytic infiltration / mononuclear cell infiltration.
- Activity of inflammation — infiltration by neutrophilic leukocytes.
- Glandular atrophy — assessed separately for the antrum and the gastric body.
- Intestinal metaplasia.
- Degree of Helicobacter pylori colonization / Helicobacter pylori density.
What non-invasive methods are used to diagnose Helicobacter pylori infection?
To diagnose Helicobacter pylori infection, a number of methods are used to examine the patient's exhaled breath, stool, and blood.
- Breath test — performing the $^{13}$C-urea breath test.
- Stool test — rapid immunochromatographic assay, detection of Helicobacter pylori antigen in stool, as well as molecular biological stool testing.
- Blood test — serological detection of antibodies against Helicobacter pylori in the blood.
To remember the action of pathogenicity factors: CagA — Cancer and Asia (Asian strains, hyperproliferation). VacA — Vacuum (extracts urea from the cell) and Ammonia (ammonia for protection against acid).
Class and exam questions
Where exactly is Helicobacter pylori localized in the stomach?
The bacterium inhabits the supraepithelial mucus layer, where it is protected from the direct action of the aggressive acidic environment of the gastric lumen.
Why does acidity decrease in pangastritis despite high gastrin levels?
Inflammatory cytokines (IL-1β, TNF-α) directly block the function of parietal and ECL cells in the gastric body, suppressing the secretion of hydrochloric acid and histamine.
How does the bacterium survive in the acidic environment of the stomach?
Using the VacA cytotoxin, the bacterium extracts urea from epithelial cells, hydrolyzes it, and creates a protective ammonia "cloud" around itself, which neutralizes acid.
What else to study on this topic
- The impact of helminth and malaria co-infection on the Th2 immune response in residents of Equatorial Africa
- Molecular mechanisms of CagA protein interaction with SHP-2 phosphatase
- The role of host genetic factors in the progression of atrophic pangastritis
- Mechanisms of lateral intercellular contact damage by VacA cytotoxin
Master the entire topic in the "Pathological Anatomy" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Helicobacter pylori gastritis" and 4,414 more pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 153 video lessons on the subject
Other topics in the «Digestive System Diseases» section
Free video lessons: pathological anatomyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.