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Pathogenesis of the Stress Response

For medical students2 min readUpdated 2026-10-10

The stress response is a complex, nonspecific bodily reaction that occurs when exposed to an extraordinary factor or when homeostatic parameters deviate from normal. The pathogenesis involves the sequential activation of nervous centers, the sympathetic nervous system, and endocrine glands to mobilize resources and adapt to extreme conditions.

Trigger mechanismExposure to an extreme factor causes afferent impulsation and activation of nervous centers.
Hormonal responseBlood levels of corticosteroids, catecholamines, glucagon, and thyroid hormones rise sharply.
Adaptation goalEvasion of the damaging factor, development of resistance, and maintenance of bodily functions.
Risk of damageA prolonged alarm stage leads to ischemia, dystrophy, ulcers, and necrosis of internal organs.
Basis of resistanceHypertrophy and hyperplasia of endocrine glands, heart, liver, and hematopoietic organs.

General Development Mechanism and Key Systems

The development of the stress response begins with a triggering moment—exposure of the body to an extreme factor or deviation of homeostatic parameters from normal values. This is followed by a cascade of reactions:

  1. Neural regulation: afferent impulsation increases, and cortical and subcortical nerve centers are activated.
  2. Activation of effector systems: effects of the sympathetic nervous system (SNS) are enhanced, and endocrine glands are stimulated.
  3. Hormonal response: the concentration of corticosteroids, catecholamines, glucagon, and thyroid hormones sharply increases in blood and tissues.
  4. Systemic effect: generalized organ hyperfunction occurs. At this stage, the maintenance of homeostasis is unstable.

To rapidly mobilize defense, compensatory, and recovery mechanisms, the sympathoadrenal system (SAS) and the hypothalamic-pituitary-adrenal (HPA) axis are activated, with the latter playing a key role. The thyroid gland and pancreas are also involved. These nonspecific mechanisms allow the body to escape the damaging factor, build resistance, and maintain vital activity.

Alarm Stage and Metabolic Support

Already in the first stage (the alarm stage), the active redistribution of resources—energy, plastic, and metabolic—begins. They are transported from non-activated tissues to dominant organs that execute specific adaptive reactions.

However, an excessively pronounced or prolonged alarm stage has a high pathogenic potential. The adaptive reaction can transform into a pathological process (disease) under the influence of the following risk factors:

With prolonged exposure to the stressor and excessive metabolic mobilization, severe consequences develop: dystrophy, hypotrophy, erosions, ulcers, and necrosis. Typical localizations of such lesions include the gastrointestinal tract, kidneys, heart, and lymphoid tissue.

Resistance Stage

The second stage of the stress response aims to build increased resistance to a specific stressor exposure. During this period, organ function normalizes, metabolic intensity stabilizes, and hormone and metabolic substrate levels even out. As a result, homeostatic parameters are maintained within a stable normal range.

The morphofunctional basis of this resistance is hypertrophy and/or hyperplasia of structural elements. These affect the tissues and organs that ensure protection:

This ensures long-term specific adaptation of the body to the action of the stress agent.

Exhaustion Stage

If the intensity of the stressor increases or its action lasts too long, compensatory and adaptive mechanisms become insufficient. This leads to the transition into the third stage—the exhaustion stage.

It is characterized by profound disruption of neural and humoral regulation mechanisms. Catabolic processes begin to dominate in tissues, and the functioning of systems and organs is impaired. The overall outcome of this stage is a sharp decrease in the body's general resistance and adaptability, leading to a failure of normal vital activity.

Mnemonic

To remember the main stress hormones, use the mnemonic CCGT: Corticosteroids, Catecholamines, Glucagon, Thyroid hormones.

Frequently asked questions

What is the mechanism of internal organ ischemia during the alarm stage?

During the alarm stage, the following sequence can lead to ischemia of individual organs and tissues:

  • Stressor/homeostasis deviation → increased afferent impulsation and activation of cortical and subcortical nerve centers.
  • Effector response → enhancement of sympathetic effects and activation of endocrine glands.
  • Hormonal response → increased blood and tissue levels of corticosteroids, catecholamines, glucagon, and thyroid hormones.
  • Hypercatecholaminemia causes vascular spasm; for the kidneys, the chain is: vascular spasm → renal ischemia → nephron death.

An excessively pronounced or prolonged alarm stage can be accompanied by ischemia of individual organs and tissues and the transition of the adaptive reaction into a pathological process. Already during the alarm stage, energy, metabolic, and plastic resources are also transported from non-activated tissues and organs to dominant organs.

How do the immune system and thymus function change during the exhaustion stage?

During the exhaustion stage, there is a general decrease in the body's resistance and adaptability against the background of neural and humoral regulation disorders, dominance of catabolic processes, and impaired organ and system functions.

For the immune system and thymus during stress, the following changes are confirmed:

  • Thymus: accidental (rapid) involution develops as a reaction to stressful situations; the triggering mechanism is exposure to high doses of glucocorticoids.
  • Thymic lymphoid cells: stress and steroid hormones are causes of their apoptosis; the thymus is sensitive to apoptosis-inducing factors.
  • Immune system: glucocorticoids weaken cellular immunity, act as immunosuppressants in high doses, and suppress immune reactions.
  • Lymphoid tissue: glucocorticoids enhance protein catabolism.

Outcome for the exhaustion stage: a decrease in the body's overall resistance and adaptability.

Which body systems play a key role in the development of the stress response?

To rapidly mobilize adaptive mechanisms, the sympathoadrenal system, thyroid gland, and pancreas are activated. However, the key role in this process belongs to the hypothalamic-pituitary-adrenal (HPA) axis.

What is the nature of metabolic support during the alarm stage?

During the alarm stage, a massive redistribution of energy, metabolic, and plastic resources occurs. They are actively transported from non-activated tissues and organs to the dominant organs responsible for executing specific adaptive reactions.

Why can prolonged stress lead to disease?

An excessively prolonged alarm stage is accompanied by hypercatecholaminemia, an excess of corticosteroids, and tissue ischemia. This exhausts the body and causes dystrophic changes, hypotrophy, erosions, ulcers, and necrosis in the GI tract, kidneys, heart, and lymphoid tissue.

What is the morphofunctional basis of the resistance stage?

Long-term adaptation is ensured by processes of hypertrophy and hyperplasia of structural elements. These changes affect endocrine glands (pituitary, adrenals, thyroid), visceral organs (heart, liver), and the hematopoietic system.

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