Gastritis — Acute and Chronic

Gastritis is inflammation of the gastric mucosa characterized by histologic evidence of leukocytic infiltration within the stomach wall, presenting across a broad spectrum from asymptomatic endoscopic findings to severe hemorrhagic disease. It represents one of the most common gastrointestinal pathologies encountered in clinical practice, affecting approximately 8% of the population at any given time, with prevalence increasing with age and in certain geographic regions. Acute gastritis typically results from mucosal injury by direct toxic, ischemic, or infectious insults and is largely reversible upon removal of the offending agent, whereas chronic gastritis results from persistent immune-mediated inflammation, most commonly from Helicobacter pylori infection or autoimmune processes, leading to progressive glandular atrophy and metaplasia. Understanding the distinction between acute and chronic forms, recognition of the underlying etiology, and appropriate endoscopic-histologic correlation are essential for appropriate management and prevention of serious sequelae including perforation, hemorrhage, and gastric malignancy.

The gastric mucosa normally maintains homeostasis through a delicate balance of aggressive factors (acid, pepsin, inflammatory mediators) and protective mechanisms (mucus layer, bicarbonate secretion, mucosal blood flow, prostaglandins, and epithelial growth factors). Gastritis develops when this protective barrier is disrupted or aggressive factors overwhelm mucosal defenses.

The gastric mucosa is protected by a 1.5-mm mucus layer composed of mucopolysaccharides secreted by gastric mucous cells, which forms a pH gradient allowing bicarbonate secretion from surface epithelial cells to create a neutral microenvironment at the epithelial surface despite luminal pH of 1-3. Prostaglandins (primarily PGE2 and PGI2) synthesized by cyclooxygenase (COX-1 and COX-2) enhance this protective layer by stimulating mucus and bicarbonate secretion while maintaining mucosal blood flow. When this barrier is disrupted—whether through nonsteroidal anti-inflammatory drug (NSAID) inhibition of prostaglandin synthesis, direct chemical injury from alcohol or bile reflux, or loss of mucosal perfusion—hydrogen ion back-diffusion occurs, leading to mucosal cell death, inflammation, and gastritis.

H. pylori, a gram-negative microaerophilic bacterium, colonizes the gastric mucosa in approximately 50% of the world's population. The organism produces urease, which generates ammonia to neutralize gastric acid in its immediate microenvironment, allowing survival in the acidic milieu. H. pylori expresses multiple virulence factors including the cag (cytotoxin-associated gene) pathogenic island, which encodes a type IV secretion system that injects bacterial proteins directly into gastric epithelial cells, triggering the production of IL-8 and other pro-inflammatory cytokines. The bacterium also produces vacuolating cytotoxin A (VacA), which creates intracellular vacuoles and induces apoptosis of gastric epithelial cells. These mechanisms trigger a Th1/Th17-predominant immune response characterized by infiltration of CD4+ and CD8+ T lymphocytes, neutrophils, and macrophages into the lamina propria and epithelium. Persistent infection leads to corpus atrophy (loss of parietal and chief cells) in approximately 10-15% of chronically infected patients, particularly in those with cag-positive strains or specific HLA polymorphisms, increasing the risk of intestinal metaplasia and subsequent gastric adenocarcinoma development.

In autoimmune gastritis (also termed Type A gastritis), loss of self-tolerance leads to generation of autoreactive B cells and CD8+ T cells specific for parietal cell antigens, particularly the gastric proton pump (H+,K+-ATPase) and intrinsic factor. These autoimmune responses result in destruction of the fundic oxyntic glands where parietal cells reside, leading to achlorhydria (absent gastric acid secretion) and loss of intrinsic factor (required for vitamin B12 absorption in the terminal ileum). Patients develop pernicious anemia from vitamin B12 deficiency, and the resultant alkaline gastric pH paradoxically allows overgrowth of gastric carcinoid tumors from enterochromaffin-like (ECL) cell hyperplasia, driven by sustained hypergastrinemia (from loss of acid-mediated feedback inhibition on gastrin-secreting antral G cells). The condition is strongly associated with HLA-DQ2 and HLA-DQ8 alleles.

When pyloric sphincter incompetence or post-gastrectomy anatomy allows bile and pancreatic secretions to reflux into the stomach, direct detergent effects on the gastric mucosa occur. Bile salts disrupt lipid membranes of gastric epithelial cells, and the osmotic load damages the mucosa. This leads to reactive inflammation characterized by foveolar hyperplasia (elongation of gastric pits) with minimal inflammatory cell infiltration, distinguishing it histologically from H. pylori gastritis.

In acute erosive gastritis, direct mucosal injury causes focal loss of epithelium extending to the muscularis mucosae but not through it (distinguishing erosions from ulcers, which breach the muscularis propria). Acute hemorrhagic gastritis develops when erosions erode into capillaries within the damaged mucosa, leading to acute bleeding that can be life-threatening in severe cases. The mechanism involves disruption of the normal vascular architecture and loss of surrounding mucosal support for hemostasis.

H. pylori is responsible for 60-90% of chronic gastritis cases globally and is the leading cause of peptic ulcer disease. Transmission occurs primarily through the fecal-oral route (contaminated water, poor sanitation) or possibly oral-oral route in developed nations. Infection is essentially lifelong without treatment and carries documented associations with intestinal-type gastric adenocarcinoma (odds ratio 2.7-3.0), gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and metaplastic polyps.

Approximately 10-25% of chronic NSAID users develop gastritis or peptic ulcer disease. NSAIDs inhibit both constitutive COX-1 (expressed in the stomach and involved in mucosal protection) and inducible COX-2 (involved in inflammation), but the loss of COX-1–derived prostaglandins in the gastric mucosa is the primary mechanism of injury. Risk is dose- and duration-dependent; concurrent use of proton pump inhibitors (PPIs) or misoprostol (a prostaglandin analog) provides gastroprotection in high-risk patients. Age >65 years, history of peptic ulcer disease, concurrent corticosteroid or anticoagulant use, and H. pylori infection amplify NSAID-related gastropathy risk.

Occurs in 1-3% of the general population (up to 10% in autoimmune-prone populations such as those with Type 1 diabetes or pernicious anemia), with female predominance (female-to-male ratio approximately 1.6:1) and age of onset typically >50 years. Associated with other autoimmune conditions including pernicious anemia, thyroiditis, celiac disease, and Addison disease. Genetic predisposition is evidenced by clustering in families and association with specific HLA alleles.

Acute alcohol consumption causes acute hemorrhagic gastritis through direct chemical injury and disruption of the mucus layer; chronic heavy alcohol use leads to chronic gastritis with atrophy. The mechanism involves oxidative stress and impaired prostaglandin synthesis. Alcohol also delays gastric emptying, prolonging mucosal contact time.

Occur in setting of severe systemic illness (sepsis, major trauma, extensive burns, critical illness), likely resulting from hypoperfusion and ischemic injury to the mucosa combined with impaired mucosal regeneration from catecholamine excess and inflammatory mediator release. The condition carries high mortality (10-40%), though incidence has declined with modern ICU management and prophylactic acid suppression.

Corrosive substances (strong acids, alkali, NSAIDs in excessive amounts), bile reflux post-gastrectomy, and aspirin cause acute hemorrhagic gastritis. Direct epithelial necrosis occurs from the caustic effect.

Cytomegalovirus (CMV) gastritis occurs predominantly in severely immunocompromised patients (CD4 count <50 cells/μL in HIV/AIDS) and presents with erosions and ulcerations. Herpes simplex virus (HSV) causes similar disease in immunocompromised hosts. Bacterial gastritis from Mycobacterium tuberculosis or atypical mycobacteria occurs in endemic regions or with advanced immunosuppression. Fungal gastritis from Candida or Histoplasma is rare and largely limited to severe immunosuppression.

Occurs when pyloric sphincter incompetence allows retrograde bile flow, particularly common post-gastrectomy or post-bilioenteric anastomosis. The alkaline bile salts cause direct mucosal injury distinct from acid-peptic damage.

Lymphocytic gastritis (increased intraepithelial lymphocytes without inflammation of lamina propria) may be associated with H. pylori infection, celiac disease, or be idiopathic. Granulomatous gastritis is rare and suggests underlying Crohn disease, sarcoidosis, tuberculosis, or fungal infection.

Acute ischemic gastritis results from severe hypoperfusion in setting of cardiogenic shock, severe sepsis, aortic dissection, or arterial insufficiency. Carries poor prognosis with high rates of transmural necrosis and perforation.

The most frequent complaint, patients describe a burning, gnawing, or aching sensation in the epigastrium that may radiate to the left upper quadrant. Pain typically occurs 30-60 minutes after eating in acute gastritis but may be food-independent in chronic disease. Severity ranges from mild dyspepsia to severe pain with acute hemorrhagic gastritis. The pain reflects mucosal inflammation and chemical irritation of nerve endings in the lamina propria and submucosa.

Results from activation of the chemoreceptor trigger zone by inflammatory mediators and from gastric dysmotility associated with mucosal inflammation. Vomiting may be non-bilious (from acute gastritis) or bilious (suggesting concurrent bile reflux gastritis). Severe vomiting can lead to dehydration, electrolyte abnormalities (hypokalemia, hypochloremia), and metabolic alkalosis.

Indicates erosive gastritis with breaching of capillaries. Coffee-ground emesis (partially digested blood from slower bleeding) versus bright red blood (more rapid hemorrhage) depends on bleeding rate and gastric emptying. This represents a medical emergency and necessitates urgent evaluation and stabilization.

Occur from mucosal inflammation and impaired gastric accommodation; patients feel full after small amounts of food, contributing to weight loss in chronic gastritis, particularly when associated with gastric atrophy.

Many patients are asymptomatic at diagnosis, discovered incidentally on screening or when investigating anemia. When symptomatic, patients report dyspepsia, dyspnea from anemia, and neuropsychiatric symptoms from vitamin B12 deficiency (paresthesias, ataxia, dementia, glossitis). Laboratory studies reveal pernicious anemia (megaloblastic anemia with hypersegmented neutrophils), elevated serum gastrin (from loss of acid-mediated feedback inhibition), low or absent gastric acid output, positive anti-intrinsic factor antibodies, and positive anti-parietal cell antibodies.

Similarly often asymptomatic, with infection discovered during evaluation for peptic ulcer disease or other complications. When gastritis is symptomatic, dyspepsia is non-specific and indistinguishable from other causes. Chronic H. pylori infection gradually leads to corpus-predominant gastritis with glandular atrophy, achlorhydria, and intestinal metaplasia—the Correa cascade—which substantially increases gastric cancer risk.

Patients may experience acute severe epigastric pain, hematemesis, or may be entirely asymptomatic despite endoscopic evidence of erosions. Risk factors for symptomatic disease and serious complications include age >65 years, prior peptic ulcer disease, concurrent anticoagulation, and dose/duration of NSAID use.

In the acute critical illness setting, patients are often sedated and unable to communicate symptoms. Occult bleeding may manifest as hemodynamic instability, falling hemoglobin, or positive fecal occult blood test. High mortality is related to underlying critical illness rather than the gastritis itself.

Typically demonstrates mild epigastric tenderness without peritonitis; severe tenderness, guarding, or rebound suggests complicated disease (perforation, severe ischemia). In patients with autoimmune gastritis, examination may reveal glossitis (smooth, red tongue), angular cheilitis, or signs of peripheral neuropathy from B12 deficiency. Hepatomegaly or splenomegaly may suggest MALT lymphoma or portal hypertension (if H. pylori led to cirrhosis).

Acute hemorrhagic gastritis may present with signs of hypovolemia: pallor, tachycardia, tachypnea, orthostatic hypotension, or shock in severe cases. Chronic gastritis with malabsorption may reveal cachexia, angular cheilitis, or glossitis from nutritional deficiency.

A rare condition characterized by giant gastric folds (>10 mm on endoscopy) with marked foveolar hyperplasia, protein-losing gastropathy, and achlorhydria. Histology shows minimal inflammation, distinguished from H. pylori gastritis. Associated with TGF-α overexpression. Presents with epigastric pain, edema from hypoproteinemia, and diarrhea. Increases gastric cancer risk. May respond to octreotide or cetuximab (anti-EGF receptor antibody).

Characterized by markedly elevated serum gastrin levels and profound gastric acid hypersecretion often associated with Zollinger-Ellison syndrome from gastrin-secreting neuroendocrine tumors. Patients present with severe, refractory peptic ulcer disease or chronic diarrhea from acid-induced small bowel injury.

Rare acute suppurative inflammation of the stomach wall (not just mucosa) caused by bacterial infection, typically from group A Streptococcus or Staphylococcus aureus, sometimes following trauma or surgery. Presents with acute severe abdominal pain, fever, and leukocytosis. High risk of perforation and requires aggressive antibiotic therapy and possibly surgical intervention.

The diagnostic approach begins with directed history eliciting onset, duration, character, and severity of symptoms; relationship to meals, NSAIDs, or alcohol; presence of hematemesis or melena; and **associated