Adrenal Medulla

1. Overview

The adrenal medulla is the innermost part of the adrenal gland and functions as a specialized neuroendocrine organ. It plays a critical role in the body’s acute stress response by secreting catecholamines—primarily epinephrine (adrenaline) and norepinephrine (noradrenaline). These hormones prepare the body for "fight or flight" situations by rapidly adjusting cardiovascular, respiratory, and metabolic functions. Unlike the adrenal cortex, the medulla is derived from neural crest cells and functions similarly to sympathetic postganglionic neurons.

2. Location

The adrenal medulla is located at the center of each adrenal gland, which sits atop the kidneys in the retroperitoneal space. It is surrounded by the adrenal cortex, which forms the outer layer of the adrenal gland. Both components are enclosed within a common connective tissue capsule.

3. Structure

The adrenal medulla is composed mainly of modified sympathetic neurons called chromaffin cells, which function as endocrine cells. These cells are arranged in clusters and cords around a rich network of sinusoidal capillaries. Chromaffin cells stain intensely due to catecholamine content and respond to sympathetic stimulation via preganglionic cholinergic fibers originating from the thoracic spinal cord (T5–T11).

4. Function

The primary function of the adrenal medulla is to secrete catecholamines directly into the bloodstream in response to sympathetic nervous system activation. The two main hormones produced are:

• Epinephrine (adrenaline): Accounts for approximately 80% of the medulla’s output. It increases heart rate, dilates airways, elevates blood glucose, and boosts oxygen delivery to tissues.

• Norepinephrine (noradrenaline): Constitutes about 20% of output. It primarily increases peripheral vasoconstriction, which raises blood pressure.

The adrenal medulla also produces small amounts of dopamine and trace amounts of other peptides such as enkephalins.

5. Physiological role(s)

The adrenal medulla is essential for rapid adaptation to stress and immediate environmental threats. Its physiological roles include:

• Fight or Flight Response: Initiates a full-body sympathetic response including increased cardiac output, bronchodilation, pupil dilation, and reduced gastrointestinal activity.

• Glucose Mobilization: Stimulates glycogenolysis and lipolysis to increase circulating glucose and free fatty acids for energy.

• Vascular Regulation: Norepinephrine increases vascular tone and blood pressure by acting on α-adrenergic receptors.

• Respiratory Enhancement: Epinephrine dilates bronchioles and increases respiratory rate, improving oxygen intake during stress.

• Thermoregulation: Catecholamines contribute to increased thermogenesis and heat production in cold environments.

6. Clinical Significance

Disorders of the adrenal medulla primarily involve abnormal secretion of catecholamines and related tumors:

• Pheochromocytoma: A rare tumor of chromaffin cells, usually benign but potentially life-threatening due to excessive catecholamine secretion. Symptoms include episodic hypertension, palpitations, sweating, anxiety, and headaches. Diagnosis involves measuring plasma or urinary metanephrines. Surgical removal is the treatment of choice.

• Paraganglioma: A similar tumor arising from extra-adrenal chromaffin tissue (sympathetic ganglia), often secreting norepinephrine. Clinical manifestations are similar to pheochromocytoma.

• Adrenal Medullary Hyperplasia: A non-tumorous enlargement of the medulla that may cause mild catecholamine excess and can be a precursor to pheochromocytoma in familial syndromes.

• Neuroblastoma: A malignant pediatric tumor derived from neural crest cells, most commonly affecting the adrenal medulla. Symptoms may include abdominal mass, weight loss, and elevated catecholamine metabolites (e.g., VMA, HVA) in urine.

• Autonomic Dysfunction: Impaired adrenal medulla function can contribute to inadequate sympathetic responses in disorders like autonomic neuropathy or adrenal insufficiency.