2017A Question 14

Outline the physiological effects of the adrenal hormones aldosterone and cortisol. (DO NOT describe synthesis or metabolism)

Examiner Report

65.5% of candidates achieved a pass in this question.

Marks were gained for a brief description of the mechanism of action of these steroid hormones, specifically that they act intracellularly on DNA transcription altering protein synthesis.

An outline of the effects of aldosterone required determining where in nephron it works, upon which cells, and which channels and pumps are involved in these actions. It was not enough to only state that aldosterone causes reabsorption of Na (and H2O by osmosis) and secretion of K. The effect upon H secretion was also expected. Better responses illustrated the numerous triggers for aldosterone release beyond just mentioning the renin-angiotensin system, and showed understanding of the triggers for renin release.

The effects of cortisol are widespread and candidates were NOT expected to cover them all to attain a pass mark, though better answers were rewarded for their breadth of understanding. The plethora of marks available was weighted towards the more important effects, and it was expected that metabolic actions (carbohydrate, protein, fat) and immune system effects would be well outlined. For example, many candidates correctly stated that cortisol stimulates catabolism. Better answers, however, would briefly elaborate to show that this provides amino acids which are then available for gluconeogenesis, and may also lead to muscle wasting... gaining several more marks in the process. Comments on catecholamine responsiveness, fetal lung maturation, CNS effects were also rewarded, as was an illustration of the hypothalamic/pituitary axis, triggers for cortisol release and feedback mechanisms.

Common errors included confusing aldosterone with ADH, and misunderstanding the terms catabolic and anabolic. Numerous candidates spent time discussing the adrenal anatomy, or the adrenal medullary hormones, and marks were not given for this.

Model Answer

Structure:

• Release stimuli
• Cellular effect
• Overall effect
• Renal effect
• GIT effects
• Sweat gland effects

Aldosterone

Property	Detail
Axis
Release stimuli	- Diurnal variation: Nadir 0000, peak 0800 - ACTH required for synthesis in adrenal cortex (zona glomerulosa) - Angiotensin 2 (major) - ↑ [K+] (minor)
Cellular effect	- Acts via mineralocorticoid receptor, a nuclear transcription factor
Overall effect	- ↑ ECF [Na+], ↓ [K+], ↑ pH, ↑ osmolality - Indirect ↑ H2O reabsorption via ↑ osmolality → ↑ ADH - Negative feedback on renin secretion by physiological effect
Renal effects	- Active in cells of connecting tubule and collecting ducts - Principal cells: ↑ Na+K+ATPase production and activity; ↑ ENaC and ROMK activity - Type 1 intercalated cells: ↑ H+ ATPase activity
GIT effects	- ↑ Na+K+ATPase and ENaC activity → ↑ Na+ and H2O reabsorption
Sweat gland effects	- ↑ Na+K+ATPase and ENaC activity → ↑ Na+ reabsorption, lower [Na+] in sweat

Cortisol

Property	Detail
Axis
Release stimuli	- ACTH required for synthesis in adrenal cortex (zona fasciculata) - Psychological stress - Physical stress: Injury, fracture, surgery, trauma, burns - ↓ BGL (sensed by hypothalamus)
Cellular effect	- Acts via glucocorticoid receptor, a nuclear transcription factor - Affects 25% of the genome - Also active at mineralocorticoid receptor, but inactivated by 11β-HSD-2 in epithelia
Metabolic effect	- Overall: Mobilise substrate for oxidation or gluconeogenesis - In excess: Visceral obesity, metabolic syndrome, proximal myopathy, osteoporosis, skin thinning, moon facies, buffalo hump - Carbohydrate: ↑↑ Gluconeogenesis (hepatic, renal), ↓ glycolysis, ↓ glycogenesis - Fat: ↑ Subcut fat lipolysis, ↑ visceral fat lipogenesis - Protein: ↑ Proteolysis (muscle, bone, skin, fascia)
Inflammatory and immune effects	- Overall: ↓ Inflammation, ↓ auto-immunity, ↑ infection, ↓ wound healing - Signalling: ↓ Eicosanoids (inhibits PLA2), ↓ some cytokines (e.g. TNFα, IL-1), ↑ other cytokines (e.g. IL-4 by TH2) - Cells: ↓ WBC chemotaxis/activation/proliferation, ↑ demargination of neutrophils, lymphopaenia, ↑ RCC, ↑ platelets
Permissive effects	- Cardiovascular: On catecholamine vasopressors - Respiratory: On catecholamine bronchodilators - Metabolic: On calorigenic effects of glucagon and catecholamines in hypothermia
Other effects	- CNS: Insomnia, depression, psychosis, impaired learning - Renal: Dilatation of afferent arteriole, ↑ GFR, diuresis and natriuresis - GIT: Peptic ulceration, pancreatitis - Eyes: Cataracts, glaucoma - Foetus: Lung surfactant production (given prior to premature delivery)