What causes gastric polyps to develop in individuals with a history of chronic gastritis, particularly those caused by Helicobacter pylori infection?

What Causes Gastric Polyps to Develop

Gastric polyps develop primarily through three distinct mechanisms: chronic inflammation from Helicobacter pylori infection (causing hyperplastic polyps), long-term proton pump inhibitor use (causing fundic gland polyps), and autoimmune destruction of gastric mucosa (causing hyperplastic polyps in the setting of autoimmune gastritis). 1

Primary Causative Mechanisms by Polyp Type

Hyperplastic Polyps (Most Common in Chronic Gastritis)

Chronic inflammation is the fundamental driver, with hyperplastic polyps arising as a by-product of repair to damaged gastric mucosa rather than occurring in normal tissue 2:

• H. pylori infection is the predominant cause, present in 25-76% of patients with hyperplastic polyps, triggering chronic active gastritis that leads to foveolar hyperplasia 1, 3, 4
• Autoimmune gastritis accounts for 12% of cases, where autoantibodies against parietal cells and intrinsic factor cause T-cell-mediated destruction of oxyntic mucosa, leading to corpus-predominant atrophy and reactive hyperplastic polyp formation 1, 4
• Chemical/reactive gastropathy (21% of cases) from bile reflux or NSAID use creates chronic mucosal injury that stimulates hyperplastic polyp development 4
• Environmental atrophic gastritis (8% of cases) from high-salt diet, tobacco use, and chronic mucosal damage progressively leads to atrophy and compensatory hyperplastic changes 1, 4

Critical mechanistic insight: After years of mucosal inflammation, gastric glands gradually decrease in size and may be replaced with connective tissue or metaplastic epithelium, creating the substrate for hyperplastic polyp formation 1

Fundic Gland Polyps

Long-term PPI use is the dominant cause (13-77% prevalence among gastric polyps), with these polyps developing through acid suppression-mediated changes in fundic gland architecture 1:

• PPIs cause cystic dilation of fundic glands with parietal cell protrusion, creating the characteristic translucent appearance 1
• These polyps can spontaneously regress when PPIs are discontinued, confirming the causal relationship 1
• Genetic predisposition in familial adenomatous polyposis (FAP) causes multiple fundic gland polyps through germline APC mutations, though this represents a minority of cases 1

Important distinction: Fundic gland polyps are NOT associated with H. pylori infection or background gastritis, unlike hyperplastic polyps 1

Barrett Esophagus-Associated Polyps

Chronic acid reflux and intestinal metaplasia at the gastroesophageal junction create a unique environment for polyp development 5:

• 33% of gastroesophageal junction hyperplastic polyps occur in association with Barrett esophagus (often ultrashort segments <1 cm) 5
• These develop without gastric pathology, distinguishing them from typical hyperplastic polyps 5
• The columnar metaplasia and chronic inflammation at the squamocolumnar junction provide the substrate for reactive hyperplastic changes 5

Pathophysiologic Cascade in H. pylori-Related Polyps

The progression follows a predictable sequence 1, 3:

1. Initial infection: H. pylori colonizes gastric mucosa, triggering chronic active inflammation
2. Atrophic changes: Over years, inflammation causes glandular loss starting in the incisura and antrocorporal transition zone 1
3. Metaplastic transformation: Lost glands are replaced by intestinal metaplasia or pseudopyloric metaplasia 1
4. Reactive hyperplasia: Ongoing inflammation stimulates foveolar hyperplasia with dilated, tortuous gastric foveoli set within inflamed, edematous stroma 2
5. Polyp formation: Focal areas of exuberant hyperplasia become polypoid lesions 4, 2

Evidence of causality: Complete regression of hyperplastic polyps occurs in 44-70% of patients after H. pylori eradication, confirming the direct causal relationship 3

Risk Factors That Modify Polyp Development

Age and demographics significantly influence polyp formation 1, 5:

• Hyperplastic polyps are most common in the seventh decade of life 2
• Autoimmune gastritis shows female predominance and increases with age 1
• Barrett-associated polyps occur in younger patients (mean age 55.9 years vs 63.0 years for gastric polyps) 5

Concurrent autoimmune diseases amplify risk 1:

• Up to one-third of patients with autoimmune thyroid disease develop autoimmune gastritis 1
• Type 1 diabetes mellitus increases autoimmune gastritis prevalence 1

Special Consideration: Hypergastrinemia-Driven Polyps

In autoimmune gastritis specifically, parietal cell loss leads to reduced gastric acid secretion, causing persistent hypergastrinemia that drives ECL cell hyperplasia and can progress to type I neuroendocrine tumors (0.4-0.7% per year incidence) 1

Common Pitfalls in Understanding Causation

Do not assume all polyps share the same etiology: Fundic gland polyps occur in the absence of gastritis and are unrelated to H. pylori, while hyperplastic polyps almost never occur in normal gastric mucosa 1, 2

Do not overlook synchronous pathology: 85% of patients with hyperplastic polyps have inflammatory mucosal pathology elsewhere in the stomach, and 6% have synchronous or metachronous adenocarcinoma, indicating that the polyp is a marker of widespread mucosal disease rather than an isolated phenomenon 4

Recognize molecular mimicry: H. pylori antigens may trigger autoimmune gastritis through molecular mimicry with gastric H+/K+ ATPase, creating overlap between infectious and autoimmune etiologies 1