17.6 The Adrenal Glands

Adrenal Gland Structure and Function

The adrenal glands sit on top of each kidney and produce hormones that regulate stress responses, metabolism, blood pressure, and electrolyte balance. Despite their small size, they're essential for maintaining homeostasis. Each gland has two structurally and functionally distinct regions: an outer adrenal cortex and an inner adrenal medulla.

The Adrenal Cortex

The adrenal cortex produces steroid hormones (derived from cholesterol) and is divided into three zones, each responsible for a different class of hormone:

• Zona glomerulosa (outermost layer): Secretes mineralocorticoids, primarily aldosterone, which regulates electrolyte and fluid balance.
• Zona fasciculata (middle layer): Secretes glucocorticoids, primarily cortisol, which regulates metabolism, the immune response, and the stress response.
• Zona reticularis (innermost layer): Secretes androgens, primarily dehydroepiandrosterone (DHEA), which contribute to sexual development and function.

A helpful mnemonic for remembering the zones from superficial to deep: GFR (Glomerulosa, Fasciculata, Reticularis). And for matching zones to their hormones: "Salt, Sugar, Sex" (mineralocorticoids, glucocorticoids, androgens).

The Adrenal Medulla

The adrenal medulla is the inner portion of the gland and produces catecholamines: epinephrine (about 80% of output) and norepinephrine (about 20%). These hormones regulate cardiovascular function and energy metabolism, and they are the primary drivers of the acute "fight or flight" response.

The medulla is functionally part of the sympathetic nervous system. Its hormone-secreting cells, called chromaffin cells, are modified postganglionic sympathetic neurons. This is why the medulla responds so rapidly to stress: it's directly activated by sympathetic preganglionic fibers rather than relying on a slower hormonal signaling cascade.

Adrenal Gland Hormones and Their Roles

Mineralocorticoids (Aldosterone)

Aldosterone acts primarily on the distal convoluted tubule and collecting duct of the kidney nephron. Its effects:

• Increases sodium reabsorption (water follows sodium, so blood volume rises)
• Increases potassium excretion
• The net result is increased blood volume and blood pressure

Aldosterone release is regulated mainly by the renin-angiotensin-aldosterone system (RAAS) and by blood potassium levels, not primarily by ACTH.

Glucocorticoids (Cortisol)

Cortisol has wide-ranging effects throughout the body:

• Raises blood glucose through gluconeogenesis (making new glucose from amino acids and glycerol in the liver) and glycogenolysis (breaking down glycogen)
• Promotes protein and lipid catabolism to mobilize energy stores
• Suppresses inflammation and the immune response, which reduces tissue damage but also makes the body more vulnerable to infection at high levels
• Follows a circadian rhythm: cortisol peaks in the early morning and drops to its lowest levels around midnight, helping regulate the sleep-wake cycle

Cortisol release is controlled by the hypothalamic-pituitary-adrenal (HPA) axis through a negative feedback loop (covered in detail below).

Catecholamines (Epinephrine and Norepinephrine)

These hormones prepare the body for immediate physical action:

• Increase heart rate, cardiac output, and blood pressure
• Dilate airways (bronchodilation) and increase respiratory rate
• Stimulate glycogenolysis and lipolysis to provide quick energy
• Redirect blood flow away from the digestive organs and toward skeletal muscles

Their effects are rapid but short-lived compared to cortisol.

The Adrenal Stress Response

The body has two overlapping but distinct pathways for responding to stress. Understanding the difference between them is a common exam topic.

Short-Term (Acute) Stress Response

This pathway is fast, acting within seconds. The sympathetic nervous system directly stimulates the adrenal medulla to release epinephrine and norepinephrine. The result is the classic "fight or flight" response:

1. A stressor is perceived (e.g., a sudden threat).
2. The hypothalamus activates the sympathetic nervous system.
3. Preganglionic sympathetic neurons stimulate the adrenal medulla.
4. The medulla releases epinephrine and norepinephrine into the blood.
5. Heart rate, blood pressure, blood glucose, and respiratory rate all increase. Blood is redirected to skeletal muscles.

These effects fade within minutes once the stressor is removed.

Long-Term (Chronic) Stress Response

This pathway is slower (takes minutes to hours) and involves the HPA axis:

1. The hypothalamus releases corticotropin-releasing hormone (CRH).
2. CRH stimulates the anterior pituitary to secrete adrenocorticotropic hormone (ACTH).
3. ACTH travels through the blood to the adrenal cortex.
4. The adrenal cortex releases cortisol (and other glucocorticoids).
5. Cortisol raises blood glucose, suppresses non-essential functions (immune activity, digestion, reproduction), and mobilizes energy stores.
6. Rising cortisol levels feed back to the hypothalamus and anterior pituitary, inhibiting further CRH and ACTH release (negative feedback).

When stress is prolonged, this negative feedback loop can become disrupted. Chronic elevation of cortisol can lead to:

• Immune suppression (increased susceptibility to infection)
• Muscle wasting from sustained protein catabolism
• Insulin resistance and hyperglycemia
• Bone loss and impaired wound healing