Modern Perspective and Etiology
In gastroenterology, there is no consensus on the exact nature of the disease. Some specialists view it as an independent nosological entity with standardized therapy. Others consider it a heterogeneous group of disorders united only by the presence of an ulcer, requiring targeted treatment based on the specific cause.
There are three main etiological factors (combinations are possible):
- Helicobacter pylori (HP) infection.
- NSAID use (causes cellular energy depletion due to COX-1 inhibition).
- Acute stress.
Additionally, ulcers can develop secondary to residual-organic central nervous system lesions (trauma, hemorrhage), where parasympathetic nervous system activation leads to gastric acid and pepsin hypersecretion.
Pathogenesis: How the Mucosa is Destroyed
Defect formation is the result of an imbalance between aggressive and protective factors. The fundamental principle is described by Karl Schwarz's postulate: "No acid, no ulcer." However, the initiating factor is most often H. pylori.
The bacterium acts on several fronts simultaneously:
- Stimulates acidity: Via signaling molecules (e.g., CagA protein), it activates G cells, which release gastrin, thereby enhancing hydrochloric acid production.
- Destroys the barrier: Reduces mucus hydrophobicity and alters the structure of the surface epithelial gel.
- Damages cells: Bacterial lipopolysaccharides bind to basement membrane laminin. Epitheliocytes lose anchorage and desquamate.
- Induces ischemia: Immune complexes with IgG deposit in small venules, activate complement, and provoke focal mucosal infarctions.
Morphological Evolution of the Defect
The process of wall destruction goes through several stages:
- Erosion: A superficial lesion where the base is the lamina propria of the mucosa. It quickly closes with regenerating epithelium beneath a "mucus-fibrin cap."
- Acute ulcer: Occurs under the continued action of aggressive factors. Proteolysis penetrates deeply, reaching the muscular layer. A zone of fibrinoid necrosis forms at the base.
- Chronic ulcer: Forms if the defect persists for 4–8 weeks. Scar tissue proliferates beneath the necrosis zone. This fibrosis impairs trophism and blocks normal regeneration.
Healing of a chronic ulcer is always incomplete (substitution) — the muscular and submucosal layers are replaced by a scar, histoarchitecture is deformed, and metaplasia may occur in the restored epithelium.
Defense Line and UACL Cells
Normally, the stomach is protected by the mucus-bicarbonate barrier. The gel physically covers the cells, and bicarbonate ions ($HCO_3^-$) create a pH gradient: from an aggressive 2.0 in the lumen to a neutral 7.0 at the epithelial surface. Key mediators of this defense are prostaglandins ($PGE_2$ and $PGI_2$).
If an ulcer does form, specific UACL (Ulcer-Associated Cell Lineage) cells appear at the bases of adjacent crypts. They stain intensely with the PAS reaction and do not divide (mitotic figures are absent). Their primary task is to secrete growth factors (epidermal growth factor, urogastrone) and trefoil peptides, which specifically bind to the defect zone and stimulate local repair.
Complications
A chronic ulcer is dangerous due to life-threatening conditions. There are four main types of complications:
- Hemorrhage — occurs from eroded vessels in the ulcer base.
- Perforation — transmural rupture of the organ wall.
- Penetration — a variant of perforation where the ulcer base becomes the wall of an adjacent organ.
- Gastric outlet obstruction — cicatricial narrowing which, when decompensated, leads to severe metabolic disturbances (chlorhydropenic uremia).