5.4
Gastritis II: Pathophysiology
The pathophysiology of gastritis begins with the colonization of the stomach lining by Helicobacter pylori (H. pylori). This bacterium spreads mainly…
H. pylori-induced gastritis begins with bacterial transmission to the gastric mucosa, commonly via contaminated food or water.
H. pylori survives the stomach's acidic environment by producing urease. Urease hydrolyzes urea into ammonia, neutralizing gastric acid locally and creating a protective microenvironment.
The bacterium then uses its flagella and mucolytic enzymes to penetrate the mucus layer and adhere to gastric epithelial cells.
This attachment initiates an immune response. Macrophages and T-cells attempt to clear the infection, but H. pylori triggers epithelial cells to express programmed death-1 ligand 1, or PD-L1. PD-L1 binds to PD-1 on T-cells, sending inhibitory signals that reduce their activity and allow immune evasion.
Simultaneously, H. pylori triggers interleukin-8 secretion, attracting neutrophils and amplifying inflammation.
H. pylori injects virulence factors like the Cytotoxin-associated gene A into host cells. This disrupts cell signaling and tight junctions, contributing to prolonged inflammation and gastritis.
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Q1: How does H. pylori survive in the stomach's acidic environment?
H. pylori produces urease, an enzyme that breaks down urea into ammonia and carbon dioxide. The ammonia neutralizes gastric acid locally, creating a protective microenvironment where the bacterium can survive and establish infection in the stomach lining.
Q2: What role does urease play in H. pylori colonization?
Urease hydrolyzes urea into ammonia, which buffers the surrounding gastric acid and allows H. pylori to survive long enough to penetrate the mucus layer. This enzyme is essential for the bacterium's initial colonization and establishment in the stomach.
Q3: How does H. pylori evade the immune system?
H. pylori induces infected gastric epithelial cells to express PD-L1, which binds to PD-1 receptors on T-cells and suppresses their activity. This immune evasion mechanism allows the bacterium to establish chronic colonization despite the host's immune response.
Q4: What is the relationship between H. pylori infection and intestinal metaplasia?
Persistent H. pylori infection causes chronic inflammation that damages gastric epithelial cells and leads to mucosal atrophy. Over time, this prolonged epithelial damage may progress to intestinal metaplasia, a precancerous change that significantly increases the risk of gastric carcinoma.
Q5: How does CagA virulence factor contribute to gastritis pathophysiology?
H. pylori injects CagA into host cells through a type IV secretion system, where it disrupts cell signaling pathways and tight junctions. This virulence factor promotes inflammation, cellular damage, and increases the risk of gastric malignancy during chronic infection.
Q6: What mechanisms allow H. pylori to penetrate the gastric mucus layer?
H. pylori uses flagella for motility and secretes mucinases to degrade the mucus layer protecting the stomach wall. These adaptations enable the bacterium to reach and adhere to underlying gastric epithelial cells, initiating the inflammatory cascade.
Q7: How does interleukin-8 amplify inflammation during H. pylori gastritis?
Infected gastric epithelial cells release interleukin-8, a chemokine that recruits immune cells such as neutrophils to the infection site. This amplifies the inflammatory response, contributing to prolonged inflammation and tissue damage characteristic of H. pylori-induced gastritis.