H.pylori gastritis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yamuna Kondapally, M.B.B.S[2]
Overview
Pathophysiology
The H.pylori induced gastritis includes the following stages: They are
- The acute gastritis
- Active chronic gastritis
- Atrophy
- Intestinal metaplasia
The acute gastritis
- In majority of patients, the initial acute phase of gastritis is subclinical (does not often give rise to clinical symptoms) 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.[1]
pathogenesis
- Following transmission, H.pylori penetrates the mucous layer of stomach 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.[2]Crabtree, J. E. "Gastric mucosal inflammatory responses to Helicobacter pylori." Alimentary pharmacology & therapeutics 10.Sup1 (1996): 29-37.
- 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 polymorph 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-α) 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.[3]
- 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.[3]
Histology
- Surface epithelial degeneration
- Increased cell exfoliation
- Increased neutrophil polymorphonuclear leucocytes in the superficial lamina propria
Active chronic gastritis
In 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.[4]
- 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 variety of cytokines including IL4, IL5 and IL6.
- These interluekins differentiate into plasma cells releasing cytokines and anti-H.pylori infection like IgM-opsonizing and complement-fixing antibodies.
- The main role of the mucosa immune response is taht the IgA prevents bacterial adhesion and IgG causes opsonisation and complement activation.
- Due to 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 development of immune response directed towards preventing the damaging effects of the H.pylori.
- Hence the persistent antigenic stimulation leads to formation of 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 mariginal 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.
Histopathogenesis
- Variable epithelial degeneration
- Neutrophil infiltration in the epithelium and the lamina propria
- Variable H.pylori colonisation
- lymphocytes and plasma cell infiltration
- Lymphoid follicles(typical feature of chronic gastritis)
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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 patients 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 are usually present in atrophic stomachs, the organisms are absent as they usually colonizes only gastric epithelium.
- As H.pylori requires partially acidic environment to thrive, hypochlorhydria is creats hostile environment to H.pylori to survive.[5]
- The metaplastic epithelium secretes acidic glycoproteins which creates more hostile environment for H.pylori.
- Hence, based on above reasons, failure3 to demonstrate H.pylori does not deny the role of 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 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 regenration follows a divergent differentiation pathway producing metaplastic glands (pseudo-pyloric appearance) which are composed of cells of the 'ulcer-associated cell lineage'(UACL).[6]
Histopathogenesis
Updated Sydney classification (Sydney criteria for gastritis)
The updated sydney classification of H.pylori induced classification include:[7]
| Feature | Non-atrophic
Helicobacter |
Atrophic Helicobacter | Autoimmune |
|---|---|---|---|
| Inflammation pattern | Antral or diffuse | Antrum & corpus, mild inflammation | Corpus only |
| Atrophy & metaplasia | Nil | Atrophy present, metaplasia at incisura | Corpus only |
References
- ↑ Sobala GM, Crabtree JE, Dixon MF, Schorah CJ, Taylor JD, Rathbone BJ; et al. (1991). "Acute Helicobacter pylori infection: clinical features, local and systemic immune response, gastric mucosal histology, and gastric juice ascorbic acid concentrations". Gut. 32 (11): 1415–8. PMC 1379180. PMID 1752479.
- ↑ Slomiany BL, Piotrowski J, Slomiany A (1998). "Induction of caspase-3 and nitric oxide synthase-2 during gastric mucosal inflammatory reaction to Helicobacter pylori lipopolysaccharide". Biochem Mol Biol Int. 46 (5): 1063–70. PMID 9861460.
- ↑ 3.0 3.1 Sobala GM, Schorah CJ, Shires S, Lynch DA, Gallacher B, Dixon MF; et al. (1993). "Effect of eradication of Helicobacter pylori on gastric juice ascorbic acid concentrations". Gut. 34 (8): 1038–41. PMC 1374349. PMID 8174949.
- ↑ Genta RM, Hamner HW, Graham DY (1993). "Gastric lymphoid follicles in Helicobacter pylori infection: frequency, distribution, and response to triple therapy". Hum Pathol. 24 (6): 577–83. PMID 8505036.
- ↑ Neithercut WD, Milne A, Chittajallu RS, el Nujumi AM, McColl KE (1991). "Detection of Helicobacter pylori infection of the gastric mucosa by measurement of gastric aspirate ammonium and urea concentrations". Gut. 32 (9): 973–6. PMC 1379031. PMID 1916500.
- ↑ Pera M, Heppell J, Poulsom R, Teixeira FV, Williams J (2001). "Ulcer associated cell lineage glands expressing trefoil peptide genes are induced by chronic ulceration in ileal pouch mucosa". Gut. 48 (6): 792–6. PMC 1728308. PMID 11358897.
- ↑ Dixon MF, Genta RM, Yardley JH, Correa P (1996). "Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994". Am J Surg Pathol. 20 (10): 1161–81. PMID 8827022.