Pathophysiology of Gastritis
Gastritis pathophysiology fundamentally involves chronic mucosal inflammation leading to progressive glandular destruction (atrophy), with two distinct pathogenic mechanisms: H. pylori-driven environmental injury versus autoimmune-mediated parietal cell destruction, both culminating in loss of gastric glands and replacement by connective tissue or metaplastic epithelium. 1
Core Pathogenic Mechanisms
The pathogenesis involves interaction between environmental and genetic factors, with the primary trigger determining the disease pattern 1:
H. pylori-Associated Gastritis (HpAG)
- Initial injury: Chronic H. pylori infection causes persistent mucosal inflammation without the bacterium crossing the epithelial barrier 2
- Immune activation: The infection provokes an immune reaction that, while unable to eradicate the bacterium, contributes significantly to mucosal damage 2
- Progressive atrophy: After years of inflammation, gastric glands gradually decrease in size and may disappear completely 1
- Anatomic progression: Atrophic changes begin in the incisura and antrocorporal transitional mucosa as small foci with gland loss and intestinal metaplasia (IM). These foci coalesce into larger patches along the lesser curvature and antrum, eventually spreading to corpus/fundus, followed by loss of gastric acidity 1
Autoimmune Gastritis (AIG)
- Autoantibody formation: Autoantibodies develop against parietal cells and intrinsic factor 1
- T-cell destruction: T-cell-mediated destruction of gastric oxyntic mucosa occurs 1
- Characteristic pattern: Results in corpus-predominant atrophy with antral sparing, distinguishing it from HpAG 1
- Lymphocytic infiltration: Individual oxyntic glands are destroyed by lymphocytes 1
Histopathologic Evolution
The atrophic process is slow, occurring over years to decades 1:
Glandular Replacement Patterns
- Nonmetaplastic atrophy: Glands replaced with connective tissue (referred to simply as "atrophy") 1
- Metaplastic atrophy: Glands replaced with different epithelium:
Common Pathway Consequences
Regardless of etiology, both HpAG and AIG lead to 1:
- Progressive loss of oxyntic glands
- Increasingly prominent pseudopyloric metaplasia and IM
- ECL (enterochromaffin-like cell) hyperplasia
- Type 1 gastric neuroendocrine tumors (NETs) - indicating hypergastrinemia 1
Functional Consequences
Acid Secretion Changes
- Parietal cell loss leads to reduced gastric acid secretion 1
- Persistent hypergastrinemia develops as a compensatory response 1
- Achlorhydria occurs in severe atrophic gastritis, causing chronic luminal alkalosis 3
Downstream Effects
The acid-free environment and alkalosis favor 3:
- Development of intestinal metaplasia
- Important intraluminal metabolic disturbances
- Nutritional deficiencies (vitamin B12, iron, calcium, magnesium, zinc) 4
Molecular and Immunologic Mechanisms
Cytokine-Driven Progression
Recent evidence demonstrates that specific immune responses drive disease stages 5:
- Type I/Th1 or Th17 responses: Drive the atrophic phase through secreted cytokines
- Type II (Th2) responses: Drive the metaplastic phase with cellular redifferentiation
- Outcome: Dysplasia of gastric epithelium, the substrate for gastric cancer 5
Potential Overlap Between Phenotypes
Molecular mimicry between H. pylori antigens and gastric H+/K+ ATPase has been proposed as a trigger for AIG, suggesting pathogenic overlap between HpAG and AIG 1
Critical Clinical Pitfalls
Important caveat: If antral atrophy is seen in AIG, concomitant HpAG should be considered, as this suggests dual pathology 1. The presence of IM on gastric histology almost invariably implies the diagnosis of atrophic gastritis 1.
The severity and topographic distribution of atrophic lesions are well-established determinants of gastric cancer risk, with extensive atrophy and metaplasia associated with increased malignancy risk 1.