Pathogenetic Mechanisms: NSAIDs and Stress
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a primary cause of gastric injury. Traditional NSAIDs inhibit not only target COX-2 (providing anti-inflammatory effects) but also COX-1. This blocks the production of prostaglandins, which are critical for mucosal regeneration. Next-generation selective NSAIDs lack this side effect because they do not affect COX-1.
True stress ulcers develop through a different pathway. Severe stress stimulates the vagus nerve (n. vagus), triggering a release of adrenaline and ACTH. This leads to a sharp spike in hydrochloric acid secretion amidst mucosal ischemia, destroying the protective mucus-epithelial barrier. In clinical practice, patients often present with a combination of stress, H. pylori infection, and NSAID use, making it vital to identify the leading etiology.
Eponymous Syndromes and Systemic Diseases
Symptomatic ulcers frequently accompany severe systemic conditions and endocrine disorders:
- Cushing ulcers: Multiple defects associated with traumatic brain injury, intracranial hemorrhage, and neurosurgical procedures, caused by acid hypersecretion secondary to high vagal tone.
- Curling ulcers: Develop in extensive burns (burn disease). Ischemia and tissue acidosis drastically impair mucosal protective properties.
- Zollinger-Ellison syndrome: A manifestation of multiple endocrine neoplasia (MEN) type I. A gastrin-producing tumor (gastrinoma) forces the stomach to produce extreme amounts of acid.
- Polycythemia vera (Polycythemia rubra vera): Increased blood viscosity and protein precipitation disrupt microcirculation, blocking epithelial turnover.
- Diabetes mellitus: Systemically impairs tissue repair capabilities, while concurrent H. pylori gastritis often acquires an autoimmune injury component.
Infections and Associated Pathologies
In addition to classic H. pylori (and related Helicobacter heilmannii), ulcers can be associated with viral infections. Herpes simplex virus type 1 (HSV-1) can persist in vagal ganglia, disrupting mediator secretion and cellular renewal. Cytomegalovirus (CMV) is common in immunosuppressed patients (HIV, radiation sickness, glucocorticoid therapy), with its histological marker at the ulcer margins being "owl-eye" cells.
In renal failure, the mucosal barrier suffers due to a combination of factors, ranging from stress-induced glucocorticoid release to hypergastrinemia, secondary hyperparathyroidism, and protein malnutrition. In primary systemic amyloidosis, proteins deposit in blood vessels, causing stenosis and ischemia of the gastric wall. Liver cirrhosis also promotes ulceration due to high H. pylori prevalence and elevated nitric oxide levels, which trigger cellular apoptosis.
Morphogenesis and the "Pipelaying Effect"
The pathological process begins with an acute erosion—the loss of mucus-secreting epithelium, exposing the lamina propria to the aggressive action of pepsin, hydrogen ions, and chloride ions. Upon transition to a chronic erosion, a zone of fibrinoid necrosis appears on the surface, though granulation tissue is still absent.
The formation of a true chronic ulcer is invariably accompanied by chronic inflammation, which prevents the epithelium from utilizing its high regenerative potential. Healing (re-epithelialization) proceeds via the "pipelaying effect":
- Epitheliocytes synthesize type IV collagen to build their own basement membrane.
- Cells migrate along this pathway, creeping over the defect.
- The basement membrane anchors to the stroma (predominantly types I and III collagens) using type VII collagen.
A critical condition for this process is clearing the ulcer base of exudate and fibrinoid necrosis. In the periulcerative zone, a specialized transient cell clone appears—UACL (ulcer-associated cell lineage). Originating from glandular isthmus stem cells, they operate under the strict control of myofibroblasts, disappearing immediately once the defect closes.
Clinical Presentation
The leading symptom is epigastric pain. It has a clear temporal relationship with meals: it may occur immediately after eating, 2–3 hours later, or on an empty stomach (including characteristic nocturnal pain).
Pain is frequently accompanied by various dyspeptic disorders. The clinical course typically exhibits pronounced seasonality, with exacerbations in spring and autumn.