The endocrine stress response !

Regulation
Exam priority: medium

In injury, surgery or infection, the body releases cortisol, adrenaline and other hormones that raise sugar, hold water and burn its own protein.

Updated 2026-11-01

Also called: Metabolic response to injury, Stress hyperglycemia

See it in 3D: Hypothalamus · Pituitary gland · Right adrenal gland · Left adrenal gland

What it is

Surgery, trauma, burns, sepsis and severe emotional stress trigger the same hormonal pattern: the HPA axis and the sympathetic–adrenal system switch on, the counter-regulatory hormones rise and the anabolic ones (insulin action, thyroid, gonadal) are turned down. The aim is short term: fuel for the brain and the immune system, defended blood pressure and volume. Sustained for days, the same pattern becomes catabolic, causing hyperglycemia, muscle loss and immune suppression.

How it works, step by step

Pain, cytokines (IL-1, IL-6, TNF-α), hypovolemia and fear reach the hypothalamus and brainstem.
The paraventricular nucleus releases CRH and ADH; ACTH rises and cortisol loses its normal circadian rhythm.
Sympathetic outflow releases norepinephrine at nerve endings and epinephrine from the medulla within seconds.
Catecholamines and cortisol raise glucagon and lower insulin action: hepatic glucose output rises and muscle uptake falls.
Cortisol mobilizes amino acids from muscle for gluconeogenesis and acute-phase proteins in the liver.
ADH and aldosterone retain water and sodium: urine output falls after surgery even with normal kidneys.
If stress persists, protein loss, insulin resistance and immune suppression add up, slowing healing.

Hormone axes and feedback

Hypothalamic–pituitary–adrenal axisLesion None (normal)

Tap a box to see the hormone, or choose a lesion to see the lab pattern.

Stimulates (+)
Inhibits / negative feedback (−)
Level ↑
Level ↓

HPA axis. Choose «abrupt glucocorticoid withdrawal» to see why a suppressed axis cannot answer stress.

Hormone changes in acute severe stress

Hormone	Change	Main consequence
Cortisol	↑ (rhythm lost)	Gluconeogenesis, proteolysis, anti-inflammatory, vascular tone
Epinephrine / norepinephrine	↑↑	Cardiac output, glycogenolysis, lipolysis
Glucagon and GH	↑	Glucose output, lipolysis
Insulin	↔ or ↑, with resistance	Hyperglycemia
ADH and aldosterone	↑	Water and sodium retention, oliguria
T3 / GnRH–LH–sex steroids	↓	Energy saving, reproduction paused

Clinical notes

Sepsis: hyperglycemia, high lactate and relative adrenal insufficiency (cortisol too low for the degree of illness) are common.
Long-term glucocorticoid users have a suppressed HPA axis; surgery or infection can then cause adrenal crisis (shock that responds poorly to vasopressors).
Stress hyperglycemia in hospital is linked to worse outcomes and can unmask diabetes.
Postoperative oliguria and mild hyponatremia are expected effects of ADH; they must be told apart from kidney injury.

Test yourself

Think of the answer, then tap the question to see it.

Why does a patient with no history of diabetes have hyperglycemia in the ICU with sepsis?

Cortisol, epinephrine, glucagon and GH raise hepatic glucose output, and cytokines plus these hormones cause insulin resistance in muscle and fat.

Why can a patient on long-term glucocorticoids collapse during surgery?

Exogenous steroids suppress CRH and ACTH and atrophy the fasciculata. Under stress the adrenal cannot raise cortisol, so vascular tone and the response to catecholamines fail.

Why does urine output fall after major surgery despite normal kidneys?

Pain, hypovolemia and stress raise ADH and activate the renin–aldosterone system, so the kidney retains water and sodium.

In prolonged critical illness, T3 is low and TSH normal. Does this mean central hypothyroidism?

Usually not. It reflects nonthyroidal illness: less T4 is converted to T3 and more to reverse T3, an adaptive energy-saving change.

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See it in 3D

The structures of Durgical's 3D anatomy where it happens.

In Biochemistry

← All of physiology

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 17.6 The Adrenal Glands (OpenStax (Rice University), 2022); Bacterial Sepsis (StatPearls (NCBI Bookshelf), 2024); Adrenal Insufficiency (StatPearls (NCBI Bookshelf), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 78). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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Representative model, for educational purposes only.