Helicobacter pylori infection

Pathogenicity factors of Helicobacter pylori

The bacterium possesses a powerful arsenal for surviving in the aggressive acidic environment and destroying the mucosa:

• Urease — an enzyme that hydrolyzes urea into ammonia and carbon dioxide. It forms an "alkaline cloud" around the microbe, neutralizing hydrochloric acid.
• Flagella and mucinases — ensure movement (chemotaxis) and liquefy the thick gastric mucus, allowing the bacterium to penetrate the epithelium.
• BabA adhesin — is responsible for the tight attachment of the microorganism to $Le^b$ blood group antigens on the surface of epithelial cells.
• CagA (pathogenicity island, type IV secretion system) — reorganizes the host cell cytoskeleton, induces the production of interleukin-8 and RANTES, which attracts neutrophils and causes powerful inflammation.
• VacA — forms pores, causes cytoplasmic vacuolization, weakens intercellular contacts, and triggers apoptosis (death) of epithelial cells.

Pathogenesis of chronic gastritis

Chronic gastritis is a morphological phenomenon. It manifests as chronic inflammation, impaired cell renewal (dysregeneration), and progressive glandular atrophy, leading to secretory insufficiency. There are three main types. Type A (about 5% of cases) is autoimmune, affecting the body of the stomach. Type C is chemical, caused by bile reflux or NSAID intake. However, the most frequent is Type B, which is bacterial gastritis associated with Helicobacter pylori.

Initially, the infection affects the antral region (endoscopically often presenting a "cobblestone" appearance). The pathogenesis is based on an imbalance: aggressive factors (bacteria, hydrochloric acid, pepsin) suppress protective factors (mucus, bicarbonates, blood flow). This induces polarization of the Th1 immune response, the release of interferon-$\gamma$ and tumor necrosis factor-$\alpha$. As a result, macrophages and neutrophils begin to damage the epithelium itself.

Morphological diagnostics

The modified Sydney system is used to assess the severity of mucosal damage. It takes into account several parameters at once: the degree of H. pylori colonization, the activity of inflammation (determined by neutrophil infiltration), the severity of chronic inflammation (by the presence of mononuclear cells), as well as the stages of atrophy and metaplasia.

The modern staging standard is the OLGA/OLGIM system. The main rule of this system is the necessity of taking exactly five biopsy specimens from strictly defined zones:

1. Two fragments from the antrum.
2. Two fragments from the body of the stomach.
3. One fragment from the angle of the stomach.

This is critically important because the detection of stage III or IV according to the OLGA system indicates that the risk of developing intestinal-type gastric cancer is increased 6-fold.

From infection to peptic ulcer disease

The long-term course of Helicobacter infection often leads to the development of the ulcer phenotype. Inflammation in the antrum (antrum gastritis) provokes hypergastrinemia — the excessive production of the hormone gastrin. This significantly enhances acid-peptic aggression, which ultimately leads to the formation of a duodenal ulcer (DU).

It is important to understand the pathogenetic differences in localizations:

• Duodenal ulcer: hydrochloric acid secretion levels are usually elevated, with the leading mechanism being the activation of aggressive factors.
• Gastric ulcer: secretion often remains normal or decreased, with the primary factors being a drop in mucosal resistance and duodenogastric reflux due to pyloric insufficiency.

In addition to essential peptic ulcer disease, there are symptomatic and acute "stress" ulcers (Curling's ulcers in burns, Cushing's ulcers in traumatic brain injuries), which are characterized by a multiple nature and a high tendency to bleed.

Cancer phenotype and the Correa cascade

An alternative scenario for long-term persistence of Helicobacter pylori is the cancer phenotype. It develops according to the pathogenetic model known as the Correa cascade. This is a strict sequence of morphological changes in the gastric mucosa:

Chronic inflammation $\rightarrow$ Glandular atrophy $\rightarrow$ Intestinal metaplasia $\rightarrow$ Dysplasia $\rightarrow$ Adenocarcinoma.

Class and exam questions

What else to study on this topic

• Classification of peptic ulcer disease according to ICD-10 (codes K25–K28, K31).
• Symptomatic gastric and duodenal ulcers (drug-induced, endocrine).
• "Stress" gastroduodenal ulcers (Curling's, Cushing's ulcers).
• Formulating a detailed diagnosis of peptic ulcer disease in pediatrics.
• Autoimmune (type A) and chemical (type C) chronic gastritis.

Other topics in the "Additional Topics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.