General Adaptation Syndrome

The Physiology of Stress: SAM and HPA Axis

When a stressor is perceived, the body responds through two integrated physiological pathways — the sympatho-adrenomedullary (SAM) system and the hypothalamic-pituitary-adrenal (HPA) axis. These systems work together to mobilise the body's resources for dealing with the threat, though they operate on different timescales and through different mechanisms.

The SAM System (Fast Response)

The SAM pathway represents the immediate, rapid stress response — sometimes called the fight-or-flight response (Cannon, 1932). When a stressor is perceived by the brain, the hypothalamus activates the sympathetic branch of the autonomic nervous system (SNS). The SNS signals the adrenal medulla (the inner part of the adrenal glands, located above the kidneys) to release adrenaline (epinephrine) and noradrenaline (norepinephrine) into the bloodstream.

These catecholamines produce the characteristic fight-or-flight physiological changes within seconds:

• Increased heart rate and blood pressure (to deliver oxygen and glucose to muscles)
• Increased breathing rate and bronchodilation
• Dilation of pupils (increased vigilance)
• Glycogen in the liver is converted to glucose (immediate energy)
• Inhibition of digestion (non-essential during acute threat)
• Increased sweating (cooling)

When the threat passes, the parasympathetic nervous system restores the body to baseline (the 'rest and digest' state). The SAM response is adaptive for acute physical threats — it prepares the body for immediate action. Problems arise when the SAM system is chronically activated by psychological stressors (work pressure, relationship conflict) that do not require physical action.

The HPA Axis (Slower, Sustained Response)

The HPA axis produces a slower but more sustained stress response through a hormonal cascade. The hypothalamus releases corticotrophin-releasing hormone (CRH), which travels via the portal blood supply to the anterior pituitary gland. The anterior pituitary responds by releasing adrenocorticotrophic hormone (ACTH) into the bloodstream. ACTH travels to the adrenal cortex (the outer part of the adrenal glands) and stimulates the release of cortisol (a glucocorticoid).

Cortisol is the primary stress hormone of the HPA axis. It sustains the stress response by: maintaining elevated blood glucose (gluconeogenesis — converting proteins and fats to glucose); mobilising energy from fat stores; and suppressing immune function (to conserve resources for immediate threat response). Cortisol also acts on the brain — affecting mood, memory, and arousal.

Negative feedback: cortisol feeds back to the hypothalamus and anterior pituitary, inhibiting further CRH and ACTH release once sufficient cortisol is circulating. This negative feedback loop limits the duration of the HPA response under normal conditions. Chronic stress can impair this feedback mechanism, leading to persistently elevated cortisol — with damaging consequences for immune function, metabolism, and brain structure (particularly the hippocampus).

Selye's General Adaptation Syndrome (GAS)

Hans Selye (1936, 1956) proposed the General Adaptation Syndrome — a three-stage model of the body's response to prolonged stress: Alarm reaction: initial SAM-mediated fight-or-flight activation, followed by a temporary reduction in resistance. Resistance: the body adapts to the stressor — HPA axis sustains cortisol output; the person appears to cope effectively whilst physiological wear is accumulating. Exhaustion: if the stressor persists, physiological resources are depleted — adrenal glands become exhausted, cortisol can no longer be maintained, immunity is severely compromised, and stress-related illness becomes likely. Selye's GAS was influential in establishing that many physical illnesses can result from prolonged psychological stress — a foundational insight of psychosomatic medicine.