Multifactorial Nature of the Disease
The development of an ulcer defect is almost never caused by a single factor alone. It is a classic multifactorial pathology where various elements mutually potentiate (enhance) each other's effects.
The primary triggers initiating the pathological process include:
- Dietary indiscretions — systematic disruption of eating habits and schedules.
- Social and psychogenic factors — frequent stress, adverse living conditions, and psycho-emotional overstrain.
- Pharmacological agents — use of ulcerogenic drugs (particularly nonsteroidal anti-inflammatory drugs).
- Infectious involvement — colonization of the mucous membrane by Helicobacter pylori.
- Internal shifts — genetic predisposition, endocrine dysfunctions, and baseline insufficiency of the defense mechanisms in the digestive tract wall.
Balance of Factors: Defense versus Aggression
The core of peptic ulcer pathogenesis is the loss of dynamic equilibrium. A mucosal defect forms when protective mechanisms are deficient while aggressive factors are excessive.
Protective Factors:
- Mucus (mucin) — forms the primary mechanical and chemical barrier.
- Bicarbonates — provide local neutralization of acid.
- Prostaglandins — critical for regulating blood flow, as well as mucus and bicarbonate secretion.
- Phospholipids — create a hydrophobic (water-repelling) layer on the epithelial surface.
- Regeneration and immunity — rapid cell repair and local immunobiological surveillance.
Aggressive Factors:
- Hypersecretion of hydrochloric acid (HCl) and pepsin.
- Bile (damages tissues during duodenogastric reflux).
- Wall ischemia due to spasms of the stomach and intestinal musculature.
- Helicobacter pylori infection and NSAID use.
There is an important topographic pattern: in gastric ulcers, the primary mechanism is a decrease in the efficiency of protective factors. Conversely, in duodenal ulcers, the leading pathogenetic link is the activation of aggressive factors (predominantly the acid-peptic factor).
Neuroendocrine Mechanisms of Pathogenesis
The common pathways of ulcer formation are often triggered by recurrent, prolonged psycho-emotional stress. This leads to stagnant excitation in the hypothalamus, which acts through three parallel cascades:
- Activation of the parasympathetic nervous system (PNS). Causes decreased production of mucus and bicarbonate alongside increased secretion of hydrochloric acid and pepsin. It induces prolonged smooth muscle spasms leading to ischemia, as well as duodenal dysmotility with bile reflux into the stomach.
- Activation of the sympathetic nervous system (SNS). Leads to vasoconstriction of arterioles in the gastric wall. The resulting ischemia triggers oxidative stress: the generation of reactive oxygen species and lipid peroxides that directly destroy cells.
- Neurohumoral shift (hypercorticism). Increased production of corticotropin-releasing hormone and glucocorticoids stimulates gastric secretion, suppresses the synthesis of protective mucus, and blocks mucosal regeneration.
All these pathways converge on a single pathophysiological outcome: the effects of acid-bile-peptic aggression begin to dominate over gastric resistance, which, combined with local pathogenic influences, leads to ulcer formation.