Pathogenesis of peptic ulcer disease

Multi-etiological nature of the disease

The development of an ulcer defect is almost never caused by a single factor alone. It is a classic multi-etiological pathology, where various factors mutually potentiate (enhance) each other's effects.

The main causes triggering the pathological process include:

• Dietary errors — systematic violation of the diet schedule and pattern.
• Social and psychogenic factors — frequent stress, unfavorable living conditions, psycho-emotional strain.
• Drug effects — use of ulcerogenic drugs (specifically, nonsteroidal anti-inflammatory drugs).
• Infectious damage — colonization of the mucous membrane by Helicobacter pylori bacteria.
• Internal shifts — genetic predisposition, endocrine dysfunctions, and initial insufficiency of defense mechanisms in the walls of the digestive tract.

Balance of factors: defense versus aggression

The central link in the pathogenesis of peptic ulcer disease is the loss of dynamic equilibrium. A mucosal defect forms with a simultaneous deficit of protective mechanisms and an excess of aggressive influences.

Protective factors:

• Mucus (mucin) — forms the primary mechanical and chemical barrier.
• Bicarbonates — provide local acid neutralization.
• Prostaglandins — critically important for regulating blood flow, as well as mucus and bicarbonate secretion.
• Phospholipids — create a hydrophobic (water-repellent) layer on the epithelial surface.
• Regeneration and immunity — rapid cell restoration and local immunobiological surveillance.

Aggressive factors:

• Hypersecretion of hydrochloric acid (HCl) and enzymes (pepsin).
• Bile (damages tissues during duodenogastric reflux).
• Wall ischemia due to spasm of the stomach and intestinal muscles.
• Impact of Helicobacter pylori and NSAID use.

There is an important topographical pattern: in gastric ulcer, the decrease in the efficiency of protective factors comes to the forefront. At the same time, for duodenal peptic ulcers, the leading pathogenetic link is the activation of aggressive factors (predominantly the acid-peptic factor).

Neuroendocrine mechanisms of pathogenesis

The general pathways of ulcer formation are often triggered by repeated, prolonged psycho-emotional stress. It leads to the appearance of a stagnant focus of excitation in the hypothalamus, which is realized through three parallel cascades:

1. Activation of the parasympathetic nervous system (PNS). Causes a decrease in the production of mucus and bicarbonates while simultaneously increasing the secretion of hydrochloric acid and pepsin. Prolonged spasm of smooth muscles occurs with the development of ischemia, as well as duodenal dyskinesia with bile reflux into the stomach.
2. Activation of the sympathetic nervous system (SNS). Leads to narrowing (vasoconstriction) of the arterioles in the stomach wall. The developing ischemia triggers oxidative stress: the generation of reactive oxygen species and lipid peroxides, which directly destroy cells.
3. Neurohumoral shift (hypercorticism). Increased production of corticotropin-releasing hormone and glucocorticoids stimulates gastric secretion, suppresses the synthesis of protective mucus, and blocks mucosal regeneration processes.

All these pathways converge into a single pathophysiological outcome: the effects of acid-bile-peptic aggression begin to dominate over the resistance of the stomach, which, against the background of local pathogenic influences, leads to ulcer formation.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of local immunobiological surveillance of the mucous membrane
• Oxidative stress and lipid peroxidation in gastric tissues
• Impact of duodenogastric reflux and bile components on the epithelium
• The role of corticotropin-releasing hormone and glucocorticoid hyperproduction in pathogenesis
• Biochemical aspects of the protective phospholipid hydrophobic layer

Other topics in "Chapter 24. Typical Forms of Digestive System Pathology"

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