12.1 - Adrenal Glands + RAAS System Flashcards
Basics of the adrenal gland
- Two of these situated just above the kidney
- Has several layers – cortex (fibrous layer for protection), cortex (corticosteroid production) and medulla (catecholamine production)
- Contained within the renal fascia
Hormones of the adrenal cortex
☞ corticosteroids
- z. glomerulosa (nearest to capsule) producing mineralocorticoids eg aldosterone
- z. fasciculata producing glucogorticoids eg cortisol, corticosterone and cortisone
- z. reticularis (nearest to medulla) producing androgens eg androstenedione (key role in production of testosterone and oestrogens) and dehydroepiandrosterone
Steroid hormones
- These are synthesised from cholesterol in adrenal glands + gonads
- Lots of enzymes convert cholesterol into different enzymes
- Lipid soluble hormones
- Bind to receptors of the nuclear receptor family to modulate gene transcription
☞ glucocorticoids
☞ mineralocorticoids
☞ androgens
☞ oestrogens
☞ progestins
What does a deficiency in 21-hydroxylase cause
- An enzyme involved in the synthesis of cholesterol → cortisol, corticosterone and aldosterone
- Therefore deficiency in some androgens and an excess in others
- This causes renal hyperplasia
How do corticosteroids exert their actions
- Corticosteroids readily diffuse across the plasma membrane
- They then bind to glucocorticoid receptors
- Binding causes dissociation of chaperone proteins
- This allows the receptor-ligand complex to translocate to the nucleus where dimerisation with other receptors, such as GREs (glucocorticoid response elements) can occur
Aldosterone
- Most abundant mineralocorticoid
- Synthesised + released by z. glomerulosa fo adrenal cortex
- Steroid hormone so lipophilic ☞ needs to be transported using carrier protein
- Carrier protein= mainly albumin + sometimes transcortin
- Aldosterone receptor is intracellular
Exerts its actions using gene transcription
- Plays central role in regulation of plasma [Na+] and [K+] and therefore blood volume → arterial blood pressure
- Achieves this by acting on the distal tubules and collecting ducts of the kidney nephrons, where it promotes Na+ reabsorbtion and K+ excretion by the Na+/K+ ATPase pump, which causes an increase in water reabsorbtion
- This consequently causes an increase in blood volume and therefore blood pressure
The RAAS
the renin-angiotensin-aldosterone system
Liver releases angiotensinogen → angiotensin I → angiotensin II
- Angiotensinogen → angiotensin I stimulated by renin, which is released by kidney. The release of renin is in turn stimulated by hypotension + hypovolaemia (decrease in renal perfusion, drop in blood pressure, increased sympathetic tone)
- Angiotensin I → angiotensin II stimulated by ACE, which is released by lungs
-
Angiotensin II has following effects to increase blood volume + blood pressure…
☞ vascular system: vasoconstriction, leading to higher blood pressure
☞ ADH secretion from the posterior pituitary. This stimulates translocation of aquaporin channels, which aids water reabsorbtion back into blood (nephrons)
☞ stimulates adrenal gland to release aldosterone, increasing expression of Na+/K+ pump, increasing reabsorbtion of Na+ (and therefore water) back into blood
What is hyperaldosteronism (primary and secondary types + causes)
Too much aldosterone produced. Two types
primary
- Due to defect in adrenal cortex
- Bilateral idiopathic adrenal hyperplasia (ie increase in cell number in adrenal glands with no known cause)
- Aldosterone secreting adrenal adenoma (Conn’s syndrome)
- Low renin levels (high aldosterone : renin ratio)
secondary
- Due to overactivity of the RAAS
- Renin producing tumour (eg juxtaglomerular tumor) – very rare
- Renal artery stenosis… this causes high renin levels (low aldosterone : renin ratio)
How are primary and secondary hyperaldosteronism distinguished from one another
primary has high aldosterone : renin ratio
secondary has low aldosterone : renin ratio
Signs + treatment of hyperaldosteronism
signs
- High blood pressure
- Stroke (caused by high BP)
- Left ventricular hypertrophy (caused by high BP)
- Hypernatreaemia (increased Na+)
- Hypokalaemia (decreased K+)
treatment
- Depends on type + underlying cause
- Aldosterone-producing adenomas removed by surgery
- spironolactone (mineralocorticoid receptor antagonist)
Cortisol (actions on different card)
- Synthesised and released by z. fasciculata in response to ACTH
- Negative feedback to hypothalamus inhibits CRH and ACTH release
- Steroid hormone so need carrier protein for aqueous mediums ☞ transcortin
- Cortisol receptor exerts its actions by regulating gene transcription
Cortisol actions
Stress (eg pain, fever, hypoglycaemia, low BP) stimulates → hypothalamus releases CRH → this stimulates anterior pituitary to release ACTH → this stimulates adrenal cortex to release cortisol → cortisol has effect on…
☞ catabolic effects: increased proteolysis (in muscle) and increased lipolysis (adipose)
☞ increased gluconeogenesis (in liver), this increases available glucose to tissues
☞ resistance to stress (inc glucose supply, increase BP by making vessels more sensitive to vasoconstriction)
☞ anti-inflammatory affects (inhibits macrophage activity and mast cell degeneration)
☞ depression of immune response
What does cortisol have a negative feedback mechanism on
hypothalamus to release less CRH
anterior pituitary to release less ACTH
Glucocorticoid actions on metabolism
- Increase glucose production, increase proteolysis + redistribution of fat
- stimulates gluconeogenesis (in liver) by increasing the activity + amounts of enzymes. As a consequence of increased glucose ⇢ stimulates insulin ⇢ increased glycogen stores
- uptake of glucose in muscle inhibited (cortisol inhibits insulin-induced GLUT4 translocation in muscle). This prevents glucose uptake so has a glucose sparing effect
Cushing’s syndrome (signs and symptoms on other card)
umbrella term for several other conditions. Due to chronic excessive exposure to cortisol
☞ external causes are most common. This is where individual is prescribed glucocorticoids
☞ endogenous causes are much rarer. They include
- Benign pituitary adenoma secreting ACTH = Cushing’s Disease
- Excess cortisol produced by adrenal tumor = Adrenal Cushing’s
- Non pituitary-adrenal tumours producing ACTH (and/or CRH) eg small cell lung cancer
