Endocrine

Question 1

Outline the physiology of the adrenal gland (70% of marks). Describe the actions of aldosterone (30% of marks).

Past question

Answer 1

The adrenal cortex:
	- Consists of 3 distinct zones (Mnemonic Go Find Rex, Make Good Sex)
		○ Zona glomerulosa - mineralocorticoids (aldosterone). Also responsible for regeneration of cortical cells
		○ Zona fasciculata - glucocorticoids (cortisol)
		○ Zona reticularis - sex hormones (DHEA)
	- The above hormones are produced on demand, rather than stored in the adrenal gland
	- All adrenocortical hormones are synthesised from cholesterol:

The adrenal medulla:
	- Derived from neural crest tissue and functionally an analogue of sympathetic postganglionic fibres of the autonomic nervous system
	- Innervated by long sympathetic preganglionic cholinergic neurons (T5-T9)
	- 2 types of chromaffin cells
		○ ~80% have large and less dense granules containing adrenaline
		○ ~20% have small and dense granules containing noradrenaline
	- Control of catecholamine secretion:
		○ Stimulated by release of acetylcholine from preganglionic sympathetic nerve fibres in greater splanchnic nerve
		○ Depolarisation of chromaffin cells --> calcium influx --> exocytosis & release of catecholamines
		○ Angiotensin II also potentiates the release of catecholamines
		○ PNMT catalyses the formation of noradrenaline to adrenaline, and is only found in the adrenal medulla and brain

Aldosterone
- C21 corticosteroid - major mineralocorticoid produced by zona glomerulosa
- Half life of 20min and transported mainly by plasma albumin and corticosteroid-binding globulin (10%)
- 90% is inactivated by single pass through liver - reduction of the double bond of the A ring of the steroid structure. Tetrahydroaldosterone is formed and conjugated with glucuronide and excreted readily by the kidney
- Physiological effects:
○ Renal
§ Binds to intracellular mineralocorticoid receptors in the principal cells of DCT & CDs –> increased Na+ absorption and potassium excretion
□ Increases Na+ entry at apical membrane through amiloride-sensitive epithelial Na+ channel
§ Induces DNA transcription, producing proteins that increase Na+/K+ ATPase in the basolateral membrane of the kidney, colon and bladder cells
§ Increases the expression of H+-ATPase in apical membrane and Cl/HCO3 exchanger in the basolateral membrane of intercalated cells
§ Increases the number of K+ channels in the apical membrane of DCT cells (enhances K+ secretion) & in GI mucosa
○ Extra renal
§ Promotes Na+ reabsorption in sweat glands, salivary glands and GI mucosa of the distal colon
- Control of secretion:
○ Aldosterone is controlled by 3 well defined mechanisms
§ ACTH - enhances aldosterone synthesis by catalysing the conversion of cholesterol to pregnenolone
§ Serum K+ - 1% increase in plasma K+ can promote the release of aldosterone from the zona glomerulosa (probably due to depolarisation of zona glomerulosa cell membrane)
§ Renin-angiotensin system
□ Renin is released by juxtaglomerular cells in response to a decrease in effective circulating blood volume due to acute hypovolaemia or hypotension
□ Renin combines with angiotensinogen (a2 globulin) to produce angiotensin I, an inactive decapeptide. Angiotensin I is then converted to Angiotensin II by ACE
□ Angiotensin II has a half life of 1-3min, and stimulates the secretion and synthesis of aldosterone by the zona glomerulosa