2017A14 Outline the physiological effects of the adrenal hormones aldosterone and cortisol.
(DO NOT describe synthesis or metabolism)

 

Aldosterone:

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:

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)

 

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