Classification and Etiology
Esophageal inflammation is divided by origin into two major groups:
- Primary esophagitis develops upon direct contact of the mucosa with damaging agents. These include chemical burns from acid and alkali solutions, thermal injuries, drug-induced damage, as well as components of gastric juice and bile.
- Secondary esophagitis occurs as a manifestation or complication of other diseases. It accompanies specific infections (tuberculosis, diphtheria, measles, scarlet fever, typhus, mycoses) or systemic disorders such as Crohn's disease.
Depending on the clinical course, the process can be acute or chronic. Acute inflammation typically presents with exudative reactions: serous, fibrinous, phlegmonous, hemorrhagic, or gangrenous inflammation. The chronic variant occurs with prolonged tissue alteration, such as from regular alcohol consumption, hot food, persistent infections, or chronic reflux.
Pathogenesis of Reflux Esophagitis
Reflux esophagitis is a specific form of chronic inflammation that serves as the morphological substrate of gastroesophageal reflux disease (GERD). It is based on dysfunction of the lower esophageal sphincter, which may result from vagotomy, peptic ulcer disease, various mechanical disorders, or systemic sclerosis (due to atrophy of the cardiac muscle fibers).
When gastric and duodenal contents are refluxed, the primary aggressive factors are bile acids. They cause intercellular edema in the stratum spinosum and functional layers of the epithelium, leading to the destruction of junctional complexes. The epithelial barrier loses its integrity, and the aggressive environment penetrates deeper, causing hyperstimulation of intraepithelial nerve receptors.
Clinically, this manifests as retrosternal pain, heartburn, and sometimes vomiting and nocturnal cough. Notably, there is no direct clinicomorphological correlation: agonizing heartburn can occur with no visible macroscopic mucosal changes, while 50% of patients with severe morphological inflammation report no heartburn at all.
Microscopic Findings and Cellular Dynamics
A histological diagnosis is made based on a combination of features, as no single feature is strictly pathognomonic:
- Proliferative acanthosis: Active division of committed cells in the basal layer (confirmed by DNA synthesis using tritiated thymidine) and downward growth of the epithelium into the lamina propria as characteristic cords.
- Papillary changes: Connective tissue papillae elongate synchronously with epithelial growth, reaching 75% of the mucosal layer thickness. Venular ectasia is observed within them due to inflammatory hyperemia, stasis, and neoangiogenesis.
- Ballooning degeneration: Hydropic changes in maturing cells of the upper epithelial layers.
- Inflammatory infiltration: Eosinophilic infiltration holds key diagnostic value. Stimulated by interleukin-5 (released by Th2 lymphocytes), eosinophils migrate intraepithelially and release major basic proteins from granules that damage cell membranes. Neutrophilic infiltration is less specific and typically reacts to necrosis products or complement components.
Simultaneously, macrophages and degranulating platelets release growth factors, stimulating fibroblasts to actively produce stromal collagen (types I and III) and fibronectin.
Macroscopy and Complications
Early macroscopic changes include focal hyperemia, edema, and mucus deposits. As the condition progresses, erosions and ulcers measuring 5 mm or more appear. They localize on the crests of mucosal folds, can merge into chains, and form a ring encompassing 75% or more of the esophageal circumference. It is important to note that an ulcer is not a manifestation, but rather a complication of esophagitis resulting from decreased epithelial resistance.
Other severe outcomes and complications include:
- Bleeding: Occurs when submucosal vessels are damaged.
- Perforation: Loss of wall integrity due to a massive burn or secondary histolysis, leading to mediastinitis, pneumomediastinum, and subcutaneous emphysema.
- Inflammatory polyps: Protrusions of granulation tissue covered by proliferating epithelium during ulcer healing.
- Strictures: Narrowing of the lumen due to intramural fibrosis, which develops when the base of the ulcer extends to the muscular layer.
- Barrett's esophagus and esophageal adenocarcinoma.