Gastritis

Etiology and Risk Factors

Acute erosive gastritis

Acute gastritis usually develops after exposure to an irritant or major physiologic insult. NSAIDs inhibit cyclooxygenase-dependent prostaglandin production, reducing mucus, bicarbonate, perfusion, and epithelial repair. Alcohol, certain drugs, bile reflux, and severe systemic illness can injure the barrier directly or impair perfusion. In shock or critical illness, splanchnic hypoperfusion is particularly important; stress-related mucosal injury is not equivalent to ordinary psychological stress (Mills & Ciorba, 2019; Norris, 2020).

Chronic gastritis: distinct pathogenic pathways

Subtype	Pathophysiologic sequence	Clinical implications
H. pylori-associated	Urease activity helps the organism survive gastric acidity; flagella support movement through mucus. Persistent epithelial and immune activation produces chronic inflammation. Predominantly antral infection may increase gastrin and acid output; corpus-predominant atrophy can reduce acid.	Frequently asymptomatic. May coexist with peptic ulcers and progress to atrophy or intestinal metaplasia; long-term gastric neoplastic risk requires context-specific assessment.
Autoimmune atrophic	Immune injury of parietal cells in the body and fundus progressively reduces acid secretion and intrinsic factor, while antral G-cell activity drives compensatory hypergastrinemia.	Iron deficiency may occur; profound intrinsic factor deficiency produces impaired vitamin B12 absorption and pernicious anemia. Long-standing atrophy may be associated with gastric neoplasia.
Reactive/chemical gastropathy	Repeated epithelial exposure to bile or pancreatic secretions, often after gastric surgery or with abnormal duodenogastric reflux; chronic NSAID exposure can also produce chemical injury.	Symptom burden is variable, and tissue injury may not correlate with dyspepsia. Histology and exposure history help distinguish this pattern from infection or autoimmunity.

Clinical distinction: Autoimmune atrophy often produces hypochlorhydria or achlorhydria despite marked hypergastrinemia. The high gastrin level reflects loss of acid-mediated negative feedback, not necessarily excessive acid secretion. This is the opposite of antral-predominant H. pylori disease that can promote duodenal ulceration (Mills & Ciorba, 2019; Norris, 2020).

Epidemiology and Clinical Context

Population context: H. pylori exposure and the prevalence of related chronic gastritis vary across birth cohorts, household exposures, and world regions. Medication-associated mucosal injury deserves particular attention in older adults and patients using NSAIDs or antithrombotics, while autoimmune gastritis merits evaluation for associated autoimmune and nutritional disorders (Mills & Ciorba, 2019; Norris, 2020).

Pathophysiology

Gastric mucosal defense and injury

The stomach withstands acid and pepsin through a mucus-bicarbonate barrier, epithelial tight junctions, rapid restitution, mucosal blood flow, and prostaglandin-supported secretion and repair. Injury occurs when noxious exposure or ischemia exceeds these defenses. Acid aggravates tissue injury, but excessive acid output is not necessary for gastritis or gastric ulceration (Mills & Ciorba, 2019).

Clinical Manifestations

Manifestations range from none to nausea, epigastric discomfort, vomiting, hematemesis, or melena. Superficial erosions may bleed substantially without forming a deep peptic ulcer. A normal or minimally abnormal abdominal examination does not exclude clinically important hemorrhage. When the causative insult is removed and perfusion restored, superficial injury may resolve relatively quickly (Norris, 2020).

Diagnostic Evaluation

• Characterize the symptom and risk context: onset, NSAID/aspirin and anticoagulant exposure, alcohol use, melena, hematemesis, early satiety, weight loss, and family or personal risk of gastric cancer.
• Suspected active H. pylori infection is usually evaluated with a urea breath test or stool antigen test when endoscopy is not otherwise indicated. Serology cannot reliably distinguish active from previously treated infection (Chaudhry & Corder, 2026).
• Suspected atrophic or autoimmune gastritis warrants correlation of endoscopic biopsy findings with complete blood count, ferritin/iron status, vitamin B12 status, and, where appropriate, intrinsic factor or parietal-cell antibodies. Antibody results alone do not establish the histologic extent of atrophy (Shah et al., 2021).
• Upper endoscopy is appropriate for suspected significant bleeding, alarm symptoms, unexplained persistent symptoms, or evaluation of atrophy, metaplasia, or alternative structural disease. Do not assume the appearance of the mucosa reliably excludes chronic inflammation.

Histologic phenotype and premalignant risk

A gastric biopsy showing active neutrophilic inflammation supports active gastritis but does not identify its cause without H. pylori assessment and exposure review. Chronic atrophic gastritis involves loss of native glands, sometimes followed by intestinal metaplasia; both the extent of atrophy and associated dysplasia change gastric-neoplasia risk. Autoimmune corpus-predominant gastritis reduces acid and intrinsic-factor production, predisposing to iron deficiency, vitamin B12 deficiency and pernicious anemia. H. pylori-associated inflammation may affect antrum, corpus or both and can progress to atrophy. Endoscopic mapping and surveillance decisions should follow the actual histology and risk context rather than a generic label of “chronic gastritis” (Mills & Ciorba, 2019; Norris, 2020).

Expected Findings

Acute versus chronic: diagnostic comparison

Feature	Acute erosive gastritis	Chronic gastritis
Time course	Abrupt or temporally associated with an exposure or systemic insult.	Persistent inflammation, sometimes with progressive glandular loss.
Dominant tissue pattern	Superficial erosions and mucosal hemorrhage may be prominent.	Inflammatory infiltrates, variable atrophy and intestinal metaplasia; erosions are not required.
Typical history	Recent NSAID or alcohol exposure, critical illness, ischemia, medication changes.	H. pylori risk, autoimmune disease, iron or B12 deficiency, prior gastric surgery.
Important complications	Upper GI bleeding; severe stress-related mucosal injury.	Peptic ulcer, glandular atrophy, nutrient deficiency, and selected gastric neoplasms.
Confirmation	Assess severity; endoscopy when indicated by bleeding, alarm features, or uncertainty.	Cause-directed H. pylori testing and, when indicated, endoscopy with systematic gastric biopsies.

Differential Diagnosis

Epigastric pain may indicate peptic ulcer disease, biliary disease, pancreatitis, functional dyspepsia, gastric outlet obstruction, or an extra-abdominal emergency such as acute coronary syndrome. Hematemesis, melena with dizziness, syncope, hypotension, peritoneal signs, or an abrupt severe abdominal pain pattern require urgent evaluation rather than empiric dyspepsia treatment (Jameson et al., 2020; Mills & Ciorba, 2019).

Diagnostic Limitations and Reassessment

Negative H. pylori testing is less dependable with recent proton pump inhibitor, antibiotic or bismuth exposure. Choose a validated test and arrange appropriate withholding intervals when safe; distinguish active-infection tests (urea breath or stool antigen) from serology, which cannot verify eradication. When autoimmune gastritis is suspected, evaluate B12, iron status and relevant antibodies in context (Chaudhry & Corder, 2026; Shah et al., 2021).

Treatment and Management

Remove avoidable mucosal irritants and correct perfusion or systemic drivers of acute injury. Acid suppression may support healing in erosive or ulcer-associated disease, but a proton pump inhibitor does not eradicate H. pylori or reverse autoimmune gland loss. Confirmed H. pylori infection requires an appropriate eradication regimen chosen against contemporary resistance guidance, followed by nonserologic confirmation of cure. Autoimmune gastritis requires surveillance for and replacement of iron or vitamin B12 deficiency, with endoscopic follow-up individualized to pathology and cancer risk (Chaudhry & Corder, 2026; Chey et al., 2024; Norris, 2020).

Premalignant pathology warrants a separate risk decision after the cause of gastritis has been addressed. The 2025 ACG gastric premalignant guideline supports surveillance, often at a three-year interval, for selected higher-risk intestinal metaplasia or moderate-to-severe atrophy, while generally advising against routine surveillance for low-risk focal or mild findings. Decisions depend on histologic subtype, anatomical extent, family and demographic risk, endoscopic quality, and patient preference. Test for H. pylori, treat if present, and document eradication in patients with gastric premalignant conditions (Morgan et al., 2025).

Complications and Red Flags

A normal or minimally abnormal abdominal examination does not exclude clinically important hemorrhage (Norris, 2020).

Clinical Reasoning Priorities

An adult taking daily ibuprofen has new melena but little abdominal pain. NSAID-related mucosal injury and peptic ulcer disease are both plausible; symptom severity cannot discriminate between them. The immediate priorities are bleeding severity, hemodynamic stability, medication exposures, and endoscopic evaluation as appropriate. By contrast, a patient with fatigue, glossitis, low vitamin B12, and autoimmune thyroid disease raises concern for corpus-predominant autoimmune atrophic gastritis even without prominent dyspepsia.

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References

Chaudhry, F., & Corder, M. M. (2026). Peptic ulcer disease. In M. A. Chisholm-Burns, J. M. Kolesar, P. M. Malone, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed., Chapter 19). McGraw Hill.

Chey, W. D., Howden, C. W., Moss, S. F., Morgan, D. R., Greer, K. B., Grover, S., & Shah, S. C. (2024). ACG clinical guideline: Treatment of Helicobacter pylori infection. American Journal of Gastroenterology, 119(9), 1730–1753. https://doi.org/10.14309/ajg.0000000000002968

Jameson, J. L., Fauci, A. S., Kasper, D. L., Hauser, S. L., Longo, D. L., & Loscalzo, J. (Eds.). (2020). Harrison’s manual of medicine (20th ed.). McGraw-Hill Education.

Mills, J. C., & Ciorba, M. A. (2019). Gastrointestinal disease. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed., Chapter 13). McGraw-Hill Education.

Morgan, D. R., Corral, J. E., Li, D., Montgomery, E. A., Riquelme, A., Kim, J. J., Sauer, B., & Shah, S. C. (2025). ACG clinical guideline: Diagnosis and management of gastric premalignant conditions. American Journal of Gastroenterology, 120(4), 709–737. https://doi.org/10.14309/ajg.0000000000003350

Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer.

Shah, S. C., Piazuelo, M. B., Kuipers, E. J., & Li, D. (2021). AGA clinical practice update on the diagnosis and management of atrophic gastritis: Expert review. Gastroenterology, 161(4), 1325–1332.e7. https://doi.org/10.1053/j.gastro.2021.06.078