Lecture 3. The Adrenal Gland

Question 1

Learning Outcomes

Answer 1

*Describe the Location & gross anatomy
*Explain the physiology of the adrenal cortex & adrenal medulla
–Morphology
–Hormones
–Disorders of adrenal function
*Relate adrenal function to other aspects of physiology (an “integrative” approach)

Question 2

Anatomy of the Adrenal Glands

Answer 2

Anatomy of the Adrenal Glands*Above kidneys
*Approx 5-10g each
*Enclosed in fibrous capsule surrounded by fat

*Contain 2 major functional regions
–Adrenal cortex
–Adrenal medulla
–Cortex and medulla possess different cell type(s) with distinct morphology and endocrine function

*Rich blood supply
–Arterial blood enters cortex and passes through cords of cells
–Blood exits via venules of the medulla
–Permits interaction between cortex and medulla

Question 3

The Adrenal Cortex

Answer 3

*Approx 75% of adrenals
*Characterised by intracellular lipid droplets
–Steroid hormone synthesis!

*3 subregions, each of which secrete different hormones (all steroids)
–Zona glomerulosa (10%); mineralocorticoids
–Zona fasciculata (75%); glucocorticoids
–Zona reticularis (15%); sex steroids

*NB mineralocorticoids and glucocorticoids are essential for life

Question 4

General Properties of Steroid Hormones (Revision)

Answer 4

General Properties of Steroid Hormones (Revision)

*Synthesised from cholesterol
*Little storage in endocrine cells
–de novo synthesis follows cell stimulus
–but, stores of cholesterol present in the cells can be rapidly metabolised

*Mostly transported bound to plasma proteins
*Steroids are lipophilic and so diffuse across the cell membrane into the blood
*Bind to intracellular receptors
*Slow, long-term actions
–Regulation of transcription

Question 5

Mineralocorticoids

Answer 5

*Regulate homeostatic control of minerals (Na+, K+/H+)
–Cation exchange
–Also see lecture notes on kidney physiology

*1ry mineralocorticoid = aldosterone
–Different to ‘classical’ neuroendocrine regulation
–Part of renin-angiotensin-aldosterone system (RAAS)
–Stimulated by ↑ angiotensin II
–Essential for Na+ maintenance

*In plasma, mostly bound to albumin

Question 6

Disorders of Aldosterone Secretion

Answer 6

*Overproduction may result from,
–Zona glomerulosa cell hyperactivity (Conn’s syndrome)
–Excessive renin secretion

*Symptoms include,
–Na+ retention, K+/H+ loss
–Hypertension (2ry to Na+/water retention)
–Alkalosis (due to H+ loss)

Question 7

Glucocorticoids

Answer 7

*Multiple physiological roles
–Metabolism (see next slide)
–↑ Appetite
–Stress response (NB stress not just psychological, but also e.g. due to trauma, infection)
–Immunosuppression
–Reduce inflammation & allergic responses
–Weak mineralocorticoid activity (NB higher blood conc, so has physical importance)
*1ry glucocorticoid in humans = cortisol
*Others = corticosterone, cortisone
*In plasma, 75% bound to transcortin (liver glycoprotein), 15% to albumin, 10% free/unbound

Question 8

Glucocorticoids: Regulation of Metabolism

Answer 8

Question 9

Disorders of Cortisol Secretion

Answer 9

Cushing’s Syndrome
–↑ Plasma cortisol caused by e.g.
*Adrenal tumour
*↑ ACTH secretion (e.g. pituitary tumour, ↓ cortisol feedback sensitivity)
*Medication

–Symptoms include
*Diabetes mellitus (↑ gluconeogenesis)
*↑ Susceptibility to infection
*Muscle wasting, thin skin (↑ protein catabolism)
*Facial and trunk obesity (fat redistribution & ↑ appetite)

Addison’s Disease
–↓ Function of adrenal cortex caused by e.g.
*Damage to adrenal or pituitary gland
*Autoimmune disease

–Symptoms include
*Hypoglycaemia
*Lethargy, lassitude
*Loss of weigh

Question 10

Adrenocortical Sex Steroids

Answer 10

*Stimulation of zona reticularis by ACTH
*Low level of steroid secretion when compared to gonads

*Primarily produces “pre-androgens”, which are converted to testosterone in target tissues
–NB In women, source of approx ½ androgens
–Negligible relevance in men

*Functional significance poorly understood
–Female 2ry sexual characteristics (esp body hair)?
–Mid-childhood growth spurt (pre-puberty)?
–Actions become more apparent in disease (esp ↑ secretion)

Question 11

Disorders of Adrenal Androgen Secretion

Answer 11

*Excessive production
–Usually, ↑ ACTH secretion
–Alternatives inc. adrenal tumour

*Symptoms inc,
–Acne–Baldness
–Hirsuitism
–Altered gonadal physiology
–Precocious puberty

Question 12

The Adrenal Medulla

Answer 12

*1ry cell type = chromaffin cells
–Considered as specialised sympathetic postganglionic neurones

*Contain sympathomimetic catecholamines
–Adrenaline (80%), noradrenaline (20%)
–Derived from tyrosine, via dopamine
–Stored in vesicles
–Released by exocytosis

*Catecholamine secretion mediated by splanchic nerves
–Stimulated by e.g. stress, pain, cold, anxiety

*Functional importance in sympathetic “fight or flight” response to acute stress

Question 13

Action of Adrenal Medullary Catecholamines

Answer 13

*Rapid, transient effect (compared to steroids)
–Short half life (t½) = few mins

*Act via plasma membrane adrenoceptors

*Multiple receptor subtypes allow tissue specificity of effect

*Effects of adrenaline include,
–↑ heart rate & cardiac contractility
–Breakdown of glycogen and fat
–↑ O2 consumption
–↑ skeletal muscle blood flow

Question 14

Disorders of Adrenal Medulla Function

Answer 14

*Pheochromocytoma: tumour of chromaffin cells (→ ↑ catecholamine output)
–Severe hypertension
–Hyperglycaemia
–↑ metabolic rate
–Arrhythmias
–Anxiety

*NB Under activity of the adrenal medulla is not a clinical problem (adrenal medulla is not essential for life)

Question 15

Summary

Answer 15

*Adrenals have different functional regions: cortex (x3) and medulla

*Aldosterone = main mineralocorticoid; regulates ion absorption

*Cortisol = main glucocorticoid; regulates stress response, metabolism, immune function, inflammation etc

*Adrenal sex steroids have subtle effects cf gonadal steroids

*Adrenaline & noradrenaline regulate sympathetic response to stress

Question 16

*What is incorrect about this statement?
–“The Flight or Fight ResponseMillions of years ago, our cavemen ancestors needed to react swiftly to any perceived threat. This flight or fight response was designed to provide quick energy for 5-10 minutes, enabling our forefathers and mothers to either do battle or run. At the first sign of perceived danger, the human brain releases a substance known as corticotropin-releasing-hormone, or CRH. CRH travels to the adrenal cortex and stimulates the release of the hormones adrenalin and cortisol.”

Answer 16

The statement about the “Fight or Flight Response” contains several inaccuracies and misconceptions. Here are the key points that are incorrect or misleading:

1. Duration of Response:
   Misleading Time Frame: The statement claims that the flight or fight response provides quick energy for “5-10 minutes.” While the initial surge of energy may last for a few minutes, the physiological changes triggered by stress hormones can persist much longer, depending on the duration of the stressor and the individual’s response. In reality, the body can remain in a heightened state of arousal for much longer if the threat continues.
2. Hormonal Pathway:
   CRH and the Adrenal Cortex: The statement inaccurately describes the pathway of how CRH functions. While it is true that corticotropin-releasing hormone (CRH) is released from the hypothalamus, it primarily stimulates the anterior pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH then travels to the adrenal cortex, stimulating the release of cortisol.
   Adrenaline (Epinephrine): Adrenaline (or epinephrine) is primarily released from the adrenal medulla in response to direct sympathetic nervous system activation, not directly from the adrenal cortex. The adrenal medulla responds quickly to stressors, while cortisol from the adrenal cortex has a more prolonged effect.
3. Adrenal Hormones:
   Terminology: The statement refers to “adrenalin” which is an older term for “epinephrine.” While both terms are correct, it’s generally more accurate to use “epinephrine” in scientific contexts.
4. Biological Context:
   Simplistic Explanation: The explanation oversimplifies a complex physiological response. The fight or flight response involves a coordinated interaction between the nervous system (specifically the sympathetic nervous system) and the endocrine system, leading to numerous physiological changes, including increased heart rate, blood pressure, respiration rate, and energy availability.

Summary
In summary, the statement inaccurately describes the duration of the flight or fight response, misrepresents the hormonal pathways involved, and simplifies a complex physiological reaction. A more accurate representation would clarify the roles of the hypothalamus, anterior pituitary, and the adrenal glands in the stress response, as well as emphasize the prolonged effects of these hormones beyond the initial minutes of the response.