Physiology chapters
Adrenal medulla
How the adrenal medulla makes and releases adrenaline and noradrenaline, their effects on the liver, muscle, fat and circulation, how they are broken down, and the features and diagnosis of phaeochromocytoma.
- The adrenal medulla is a modified sympathetic ganglion: chromaffin cells are stimulated by preganglionic fibres (ACh on nicotinic receptors) and release about 80% adrenaline and 20% noradrenaline.
- Adrenaline raises blood glucose (liver glycogenolysis and gluconeogenesis), mobilises fatty acids (lipolysis) and breaks down muscle glycogen, while increasing heart rate and output.
- Phaeochromocytoma causes episodic hypertension, headache, sweating and palpitations; diagnosed by raised metanephrines.
On this page
Overview
The adrenal medulla forms the centre of the adrenal gland. It behaves like a sympathetic ganglion whose postganglionic cells release their transmitters into the blood as hormones.
Its cells, called chromaffin cells, come from the neural crest.
Hormones and control
- The medulla releases about 80% adrenaline (epinephrine) and 20% noradrenaline (norepinephrine), plus a little dopamine.
- It is controlled by sympathetic preganglionic fibres (from T5–T9 roughly, via the splanchnic nerves), which release acetylcholine onto nicotinic receptors on chromaffin cells.
- Release rises in stress: fear, exercise, cold, low blood glucose, bleeding.
The adrenal medulla is supplied by preganglionic sympathetic fibres; it has no postganglionic neurons of its own.
Synthesis of catecholamines
Tyrosine → DOPA → dopamine → noradrenaline → adrenaline
| Step | Enzyme |
|---|---|
| Tyrosine → DOPA | Tyrosine hydroxylase (rate-limiting) |
| DOPA → dopamine | DOPA decarboxylase |
| Dopamine → noradrenaline | Dopamine β-hydroxylase (inside vesicles) |
| Noradrenaline → adrenaline | PNMT (phenylethanolamine N-methyltransferase) |
Cortisol from the surrounding cortex flows through the medulla in the adrenal portal blood and induces PNMT. This is why the medulla makes mostly adrenaline, while sympathetic nerve endings (no PNMT) release noradrenaline.
Cortisol induces PNMT, linking stress hormones of the cortex and medulla.
Actions of adrenaline
Adrenaline acts on α and β receptors. It has a stronger effect than noradrenaline on β receptors, so it has more effect on the heart and metabolism; noradrenaline mainly causes vasoconstriction (α1).
Metabolic actions (the main exam focus)
| Tissue | Effect | Receptor | Result |
|---|---|---|---|
| Liver | ↑ Glycogenolysis and gluconeogenesis | β2 (and α1) | ↑ Blood glucose |
| Skeletal muscle | ↑ Glycogenolysis | β2 | Glucose used inside muscle for energy; lactate released (later used by the liver) |
| Adipose tissue | ↑ Lipolysis (hormone-sensitive lipase) | β1 / β3 | ↑ Free fatty acids and glycerol for fuel |
| Pancreas | ↓ Insulin (α2), ↑ glucagon (β) | α2 | Supports high glucose |
| Whole body | ↑ Metabolic rate (up to about double) | β | More heat and O2 use |
Muscle lacks glucose-6-phosphatase, so muscle glycogen cannot release free glucose into the blood. It is used by the muscle itself or leaves as lactate.
Circulatory and other actions
- Heart: ↑ rate and force (β1); ↑ cardiac output.
- Vessels: constriction in skin and gut (α1); dilation in skeletal muscle (β2) with adrenaline.
- Blood pressure: systolic rises; adrenaline at low doses may lower diastolic (β2 dilation); noradrenaline raises both.
- Airways: bronchodilation (β2).
- Eye: pupil dilation.
- CNS: alertness and arousal.
The hormonal effects last 5–10 times longer than direct nerve effects, because the hormones are removed slowly from the blood.
Breakdown
- Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT), mainly in the liver.
- End products: vanillylmandelic acid (VMA), metanephrine and normetanephrine, excreted in urine.
- At nerve endings, most noradrenaline is removed by re-uptake.
Clinical relevance
Phaeochromocytoma
How it happens: a tumour of chromaffin cells, usually in the adrenal medulla, making excess catecholamines. Some are inherited (MEN 2, von Hippel-Lindau, neurofibromatosis). An older teaching is the "rule of 10s" (about 10% bilateral, 10% outside the adrenal, 10% malignant), though inherited cases make some of these figures higher.
What you see:
- Hypertension, often episodic (paroxysms) and sometimes severe.
- Classic triad: headache, sweating (diaphoresis) and palpitations.
- Anxiety, tremor, pallor, weight loss, high blood glucose.
Diagnosis: raised plasma or urine metanephrines (and VMA); then imaging.
Treatment: α-blockade first (phenoxybenzamine), then β-blockade if needed, then surgical removal.
In phaeochromocytoma, give an α-blocker before a β-blocker. A β-blocker alone removes β2 vasodilation and leaves α1 vasoconstriction unopposed, which can cause a hypertensive crisis.
Stress hyperglycaemia
How it happens: adrenaline and cortisol in severe illness or surgery.
What you see: high blood glucose even in non-diabetics.
Adrenaline in anaphylaxis
Intramuscular adrenaline reverses anaphylaxis by α1 vasoconstriction (raising blood pressure), β2 bronchodilation and stabilising mast cells. Follow local guidance on doses.
Expect: the ratio of adrenaline to noradrenaline, preganglionic control, the synthesis pathway with tyrosine hydroxylase as the rate-limiting step, cortisol and PNMT, the metabolic actions on liver, muscle and fat, breakdown to VMA and metanephrines, and the features, diagnosis and drug order in phaeochromocytoma.
Quick revision
- Chromaffin cells (neural crest); preganglionic sympathetic control (ACh, nicotinic).
- About 80% adrenaline, 20% noradrenaline.
- Tyrosine hydroxylase rate-limiting; PNMT makes adrenaline; cortisol induces PNMT.
- Liver: glycogenolysis and gluconeogenesis. Muscle: glycogenolysis to lactate. Fat: lipolysis.
- Breakdown by MAO and COMT to VMA and metanephrines.
- Phaeochromocytoma: episodic hypertension, headache, sweating, palpitations; α-block first.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
What does the adrenal medulla secrete?
Mainly adrenaline (about 80%) and noradrenaline (about 20%).
Why does the adrenal medulla make mostly adrenaline?
Cortisol reaching it from the adrenal cortex induces the enzyme PNMT, which converts noradrenaline to adrenaline.
What are the metabolic effects of adrenaline?
It raises blood glucose by liver glycogenolysis and gluconeogenesis, breaks down muscle glycogen, and increases lipolysis in fat.
What is a phaeochromocytoma?
A catecholamine-secreting tumour of chromaffin cells, causing episodic hypertension, headache, sweating and palpitations.