H.pylori gastritis pathophysiology

# Overview
The H. pylori induced gastritis includes the following stages. They are acute gastritis, active chronic gastritis, atrophy and intestinal metaplasia.

# Pathophysiology
- The H. pylori induced gastritis includes the following stages: They are
- The acute gastritis
- Active chronic gastritis
- Atrophy
- Intestinal metaplasia
- The H. pylori induced gastritis is classified based on location into:
- Antral predominant gastritis
- Corpus predominant gastritis

# The acute gastritis
- In the majority of patients, the initial acute phase of gastritis is subclinical and is of short duration (about 7 to 10 days).
- The organisms are spontaneously cleared in a small minority of people, especially in childhood.
- In the majority of cases, the infection is not eliminated and there will be gradual accumulation of chronic inflammatory cells over the next 3 or 4 weeks.

## pathogenesis
- Following transmission, H. pylori penetrates the gastric mucosa and multiplies close to the surface epithelial cells.
- Following adhesion to epithelial cells, the bacteria releases lipopolysaccharides (endotoxin) and chemotactic mediators which penetrate the surface epithelial cells.
- These bacterial factors attract the polymorphonuclear leukocytes to the site of infection and also caused mast cell degranulation, which releases acute inflammatory mediators. Mast cell degranulation leads to:
- Increased vascular permeability
- Increased polymorphonuclear leukocytes emigration
- Increased expression of leukocyte adhesion molecules
- The platelet activating factors (PAF) released from mast cells causes microthrombosis in mucosal capillaries resulting in hypoxic injury to the epithelium
- The macrophages release IL-1 and tumor necrosis factor alpha (TNF-) which stimulates gastric epithelium to produce IL-8.
- The acute phase is associated with profound hypochlorhydria and a decreased ascorbic acid secretion into the gastric juice.
- The acid output reaches pre-infection levels after several weeks but the ascorbic acid remains lower than normal for the duration of chronic gastritis, indicating that it is due to persisting inflammation rather than hypochlorhydria.

### Microscopic pathology
- Surface epithelial degeneration
- Increased cell exfoliation
- Increased neutrophil polymorphonuclear leucocytes in the superficial lamina propria

# Active chronic gastritis
In the majority of cases, the H. pylori infection persists leading to accumulation of large number chronic inflammatory cells leading to active chronic gastritis.

## Pathogenesis
- The major diagnostic feature of chronic gastritis is an influx of lymphocytes and plasma cells (normally the antral mucosa is devoid of plasma cells and lymphocytes). Hence the presence of these cells is indicative of gastritis.
- H. pylori colonizes more in the antrum than the corpus. Hence there is increased inflammatory cell infiltration in the antrum.
- The direct acting antigens of H. pylori like lipopolysaccharides, urease etc along with interleukins 1 and 6, activate T-helper cells which produce the variety of cytokines including IL4, IL5, and IL6.
- These interleukins differentiate into plasma cells releasing cytokines and anti-H.pylori infection like IgM-opsonizing and complement-fixing antibodies.
- The main role of the mucosa in the immune response is that the IgA prevents bacterial adhesion and IgG causes opsonization and complement activation.
- Due to the acidic environment, the antibodies produced quickly lose their adhesive properties and catalase produced by H. pylori protects against polymorphs.
- However, this immune response is insufficient to eradicate the organism leading to the development of immune response directed towards preventing the damaging effects of the H. pylori.
- Hence the persistent antigenic stimulation leads to the formation of lymphoid follicles, which is the consistent feature of chronic H. pylori infection.
- These lymphoid follicles in the gastric mucosa constitutes mucosa-associated lymphoid tissue (MALT) from which gastric marginal zone B-cell lymphoma (MALToma) arises.
Also, these polymorphs accumulate around the pit isthmus, which is a proliferative compartment, causing lethal damage to stem cells resulting in glandular atrophy.

### Microscopic pathology
- Variable epithelial degeneration
- Neutrophil infiltration in the epithelium and the lamina propria
- Variable H. pylori colonization
- Lymphocytes and plasma cell infiltration
- Lymphoid follicles (typical feature of chronic gastritis)
Sydney system of grading of chronic gastritis

# Atrophy
Atrophy of stomach is defined as loss of glandular tissue due to continuous mucosal injury. This leads to thinning of gastric mucosa.
- The prevalence and severity of atrophy of stomach increases with age among the patient's chronic gastritis due to longer duration of H. pylori infection.
- Due to glandular atrophy, the prevalence of H. pylori positivity decreases. The main reasons are as follows:
- Due to intestinal metaplasia that is usually present in atrophic stomachs, the organisms are absent as they usually colonize only gastric epithelium.
- As H. pylori requires partially acidic environment to thrive, hypochlorhydria creats hostile environment to H. pylori to survive.
- The metaplastic epithelium secretes acidic glycoproteins which create the most hostile environment for H. pylori.
- Hence, based on above reasons, failure to demonstrate H. pylori does not deny the role of the organism in atrophic gastritis.

## Pathogenesis
- The continuous mucosal injury due to long-standing H. pylori infection, leads to atrophy of stomach.
- This continuous pathological process results in erosion or ulceration of the mucosa leading to the destruction of the glandular layer and followed by fibrous replacement.
- The destruction of the glandular basement membrane and the sheath of supporting cells prevents orderly regeneration. This uneven regeneration follows a divergent differentiation pathway producing metaplastic glands (pseudo-pyloric appearance) which are composed of cells of the 'ulcer-associated cell lineage'(UACL).

### Microscopic pathology
- Reduced number of oxyntic cells. No intestinal metaplasia
- The mucosa is infiltrated with neutrophils
- H. pylori is not seen on H&E stain. immunohistochemical stain of H. pylori detects the organisms.

# Intestinal metaplasia
- The intestinal metaplasia increase in prevalence according to duration of H. pylori infection.
- The damaged epithelium by H. pylori infection will be further eroded by bile reflux and replaced by intestinal type cells during the regenerative process. This metaplasia is transient but with repetitive injury it aggravates and become more permanent.
- Hence H. pylori infection and bile reflux are independent risk factors for intestinal metaplasia of stomach.
- Intestinal metaplasia is a protective mechanism as H. pylori does not attach to intestinal-type cells and also intestinal cells are more resistant to damaging effects of bile than gastric mucosa.

### Microscopic pathology
- Absence of H. pylori
- Gastric mucosal cells replaced by epithelium resembling intestinal cells

# Updated Sydney classification (Sydney criteria for gastritis)
The updated sydney classification of H. pylori induced classification include: