Outline the physiology of the adrenal gland (70% of marks).
Describe the actions of aldosterone (30% of marks).
Lack of breadth and detail were in many of the answers. Physiology of the adrenal gland includes an outline of the adrenal medulla, the types of chromaffin cells, hormones secreted and how secretion is stimulated. The three zones of the adrenal cortex should have been outlined including substances secreted, their function and again how their secretion is stimulated. The actions of aldosterone should have been described; a comment on sodium and water excretion was insufficient to attain many marks for this section. The extra-renal actions of aldosterone were missing from most answers.
- Adrenmal glands have four functionally and anatomically distinct regions:
- Zona glomerulosa, which secretes mainly aldosterone
- Zona fasciculata, which secretes mainly cortisol
- Zona reticularis, which secretes mainly androgens
- Medulla, a modified sympathetic ganglion that secretes catecholamines
(80% adrenaline, 20% noradrenaline), composed of chromaffin cells
- Steroid synthesis in the cortex is from stored cholesterol vesicles, and occurs on demand, on the time scale of minutes
- Cortisol release is approximately 30mg/day, with a maximum of around 300mg/day
- It occurs primarily in response to pituitary ACTH release, modulated by catecholamines, angiotensin II and vasopressin
- Pituitary ACTH is released in a circadian pulse, and also in response to stress of different forms (eg. pain, distress, hypotension, inflammatory cytokines)
- Glucocorticoid feedback to the pituitary and hypothalamus downregulates ACTH secretion
- Steroid receptors are mainly nuclear transcription factors that regulate gene transcription, and can either increase or decrease protein synthesis.
- Catecholamine synthesis in the medulla is a constant process that replenishes catecholamine stores, as there is a constant rate of secretion
- Catecholamines are stored in chromaffin granules from which they are released by exocytosis
- Adrenaline release in the absence of stress is about 150 μg/day
- It can increase up to sixty times in times of stress, over the time scale of seconds
- Release is stimulated by preganglionic sympathetic innervation of the adrenal medulla, with acetylcholine as the neurotransmitter, binding to nicotinic receptors on the chromaffin cells and depolarising them, resulting in granule exocytosis
- Catecholamine receptors are mainly G-protein coupled receptors and they extert their effect by increasing (α-1, β) or decreasing (α-2) the concentration of intracellular cAMP
Aldosterone, for 30% of the marks:
- Biology: a steroid hormone, similar to cortisol
- synthesised from cholesterol in the zona glomerulosa of the adrenal cortex
- Stimulus: hypovolemia, sodium depletion, hyperkalemia
- Sensor: zona glomerulosa cells of the adrenal cortex
- Afferent: RAAS (via angiotensin), pituitary (via ACTH) and directly (potassium)
- Efferent: aldosterone secretion and binding to widespread intracellular receptors
- Mineralocorticoid receptors are intracellular nuclear transcription factors, related to the glucocorticoid receptors
- Effectors: Numerous targets, but mainly vessel smooth muscle and renal tubule
- Effect: vasoconstriction, salt and water retention, potassium excretion
- Volume effects are mediated by the action of the ENaC channel in the collecting duct, which allows the reabsorption of sodium