Adrenal Medulla

The adrenal medulla is the inner core of the adrenal gland and is functionally and embryologically distinct from the surrounding adrenal cortex. It acts as a specialized sympathetic ganglion that secretes catecholamines — primarily epinephrine and norepinephrine — directly into the bloodstream in response to stress. The adrenal medulla plays a key role in the body’s acute stress response, commonly known as the “fight or flight” response.

Embryological Origin

• Derived from neural crest cells (ectodermal origin)
• Same origin as sympathetic ganglia and peripheral autonomic neurons
• Medullary cells are modified postganglionic sympathetic neurons that have lost axons and instead release neurotransmitters (catecholamines) into circulation

Histological Features

Under microscopy, the adrenal medulla is distinguishable from the cortex due to its basophilic staining and different cell morphology:

• Cell type: Chromaffin cells (also called pheochromocytes)
• Arrangement: Irregular clusters or cords surrounded by sinusoidal capillaries
• Cytoplasm: Basophilic with granules containing catecholamines
• Staining: Chromaffin reaction — when treated with chromium salts, cells stain brown due to catecholamine oxidation

Hormone Secretion

The adrenal medulla functions as an endocrine organ that releases catecholamines into the blood rather than into synaptic clefts. Its two major hormones are:

Catecholamine	Percentage	Primary Effects
Epinephrine (adrenaline)	~80%	Increases heart rate, bronchodilation, glycogenolysis, lipolysis, vasodilation in skeletal muscle
Norepinephrine (noradrenaline)	~20%	Vasoconstriction, increases blood pressure, peripheral vascular resistance

Other Secretions:

• Dopamine: Secreted in small amounts; precursor to norepinephrine
• Enkephalins: Endogenous opioid peptides co-secreted by medullary cells

Regulation

Unlike the adrenal cortex, the adrenal medulla is regulated neuronally rather than hormonally:

• Innervated by preganglionic sympathetic fibers from spinal cord segments T5–T9 via the greater splanchnic nerves
• Acetylcholine released by preganglionic fibers binds to nicotinic receptors on chromaffin cells
• This stimulation causes exocytosis of catecholamine-containing vesicles into the bloodstream

Triggers for Secretion:

• Physical or emotional stress
• Hypoglycemia
• Trauma, pain, cold exposure
• Exercise

Mechanism of Action and Receptor Targets

Catecholamines bind to adrenergic receptors throughout the body:

• α1 receptors: Vasoconstriction, increased peripheral resistance, pupil dilation
• β1 receptors: Increased heart rate and contractility
• β2 receptors: Bronchodilation, vasodilation in skeletal muscle, glycogenolysis

These receptors are G-protein-coupled and initiate diverse intracellular signaling cascades depending on tissue type.

Metabolism of Catecholamines

Once secreted, catecholamines have a short half-life and are rapidly broken down by the following enzymes:

• COMT (Catechol-O-methyltransferase)
• MAO (Monoamine oxidase)

The primary metabolites measurable in urine or plasma are:

• Metanephrine and normetanephrine (via COMT)
• Vanillylmandelic acid (VMA) – final end product excreted in urine

Clinical Significance

Pheochromocytoma

• A catecholamine-secreting tumor of the adrenal medulla (chromaffin cells)
• Symptoms: Episodic headache, sweating, palpitations, hypertension, tremor, anxiety
• Diagnosis: Elevated plasma metanephrines or 24-hour urinary catecholamines
• Treatment: Surgical removal after α-blockade (e.g., phenoxybenzamine)

Neuroblastoma

• Malignant tumor of sympathetic origin, often arising from adrenal medulla in children
• Symptoms: Abdominal mass, weight loss, catecholamine-related symptoms
• Markers: Elevated urinary VMA, HVA (homovanillic acid)

Adrenalectomy Considerations

• During adrenal gland removal, manipulation of medullary tissue can cause a catecholamine surge
• Preoperative α-blockade is essential to prevent intraoperative hypertensive crisis

Functional Anatomy and Integration

• The adrenal medulla functions as an endocrine extension of the sympathetic nervous system
• Its direct release of hormones into the bloodstream allows for widespread, rapid effects on multiple organ systems
• Its proximity to the zona reticularis enables potential paracrine interactions between glucocorticoids and catecholamines

Pharmacological Applications

• Epinephrine (adrenaline): Used in anaphylaxis, cardiac arrest, and as a vasoconstrictor in local anesthesia
• Adrenergic receptor agonists/antagonists: Widely used in cardiology, pulmonology, psychiatry