52.2 Endocrine Involvement in Secondary Hypertension Flashcards
Which system is in control of long term blood pressure regulation?
Renin-angiotensin-aldosterone axis (RAAS)
Describe the RAAsystem
What is the effect of angiotensin II on circulation?
Vasoconstrictor
What is the purpose of the RAAS system? Why is this important clinically?
Raise blood pressure = antagonists can be used to LOWER blood pressure
Which cells release renin?
Juxtaglomerular apparatus
What causes renin release from the JGA? (4)
- Reduce pressure in afferent arteriole (detected by baroreceptors in afferetn arteriole), increase renin secretion
- Sympathetic stimulation via beta 1 receptors, increase renin secretion
- Na+ enters macula densa via NKCC transporter, prostaglandins used to stimulate, adenosine to inhibit renin secretion (more sodium = less renin release, reduced sodium delivery = more renin release)
- Negative feedback via AT1 receptors, means antagonists or ACE-Is increase renin
What are the three main classes of anti-hypertensive drugs that modulate the RAA axis that you need to know about?
- ACE inhibitors
- Angiotensin receptor blockers
- Renin inhibitors
What is the action of ADH?
Secretion controlled by nerve impulses from the hypothalamus. Hypothalamic-pituitary axis.
ADH → V1a/b + V2
*V1a in blood vessels → vasoconstriction
*V1b in pituitary → ACTH release → cortisol release
*V2 in renal CD → AQP2 insertion → ↑ water retention → ↑ circulating volume
increases blood pressure
What is the action of aldosterone?
mineralocorticoid receptors in DCT/ CD → ↑ Na+ retention/ K+ excretion mediated by ENaC/
Secreted when increased circulating ATIII
What are other neuroendocrine factors that contribute to long-term ABP control?
*Natriuretic peptides (ANP/ BNP) → respond to stretch in atria/ ventricles → ↑ renal Na+/ water excretion + vasodilation → ↓ systemic BP
*Insulin resistance + HT correlation
Suggested abnormal SNS activation/ Na+ retention involved
DM2 patients respond better to certain antiHTsives → imp factor to consider.
What is aldosterone and where/how does it act?
- Steroid hormone secreted by the adrenal cortex (zona glomerulosa)
- Acts on the kidney through:
- Classical steroidal pathway
- Aldosterone binds to a cytoplasmic receptor which is then translocated to the nucleus for the transcription of proteins involved with Na+ reabsorption, including: ENaC, Na+/K+ ATPase, metabolic enzymes to generate more ATP to fuel the pump
- Non steroidal pathway
- Receptor activates PKC and PKD through increasing [Ca+] intracellularly, which increases the activity of a variety of transport proteins within epithelial cells
- Classical steroidal pathway
- Aldosterone acts to promote Na+ retention (and therefore also K+ excretion)
What are the effects of aldosterone on:
- Renal function
- Vascular tone
- Circulating volume
- Renal function -> Increases sodium reabsorption and potassium excretion
- Vascular tone -> Increases vascular tone due to endothelial dysfunction and enhances the pressor response to catecholamines and up‐regulation of angiotensin II receptors
- Circulating volume -> Increases circulating volume
What are the effects of cortisol on:
- Renal function
- Vascular tone
- Circulating volume
- Renal function -> Increases GFR by increasing glomerular blood flow and increases phosphate excretion by decreasing its reabsorption in the proximal tubules. In excess, cortisol has aldosterone-like effects in the kidney causing salt and water retention.
- Vascular tone -> Increases vascular tone
- Circulating volume -> Increases circulating volume indirectly by promoting Na+ reabsorption.
What are the effects of adrenaline on:
- Renal function
- Vascular tone
- Circulating volume
- Renal function -> Decreases flow to kidneys by increasing the resistance in all renal vascular segments, leading to antidiuresis
- Vascular tone -> Initially vasoconstriction, with prolonged exposure leads to vasodilation.
- Circulating volume -> Increases circulating volume through action on adrenal cortex to secrete aldosterone
Which are the main glands involved in secondary hypertension?
Posterior pituitary, adrenal gland
What does the adrenal medulla secrete?
The catecholamines noradrenaline and adrenaline
What does the adrenal cortex secrete?
The steroid hormones: cortisol, aldosterone, androgens
What is a phaeochromocytoma?
A tumour of the chromaffin cells in the adrenal medulla
What does phaeochromocytoma cause?
Excess adrenaline/noradrenaline release
–> hypertension, headache, sweating, anxiety
What are the effects of cortisol on the renal system?
- Increases glomerular filtration rate (by increasing glomerular blood flow)
- Increases phosphate excretion
- Has aldosterone-like effects as able to bind to aldosterone receptor –> sodium and water retention
What is the role of cortisol in terms of blood volume and blood pressure?
Helps maintain normal blood volume/pressure
What is the effect of adrenaline on the renal system?
Decreases renal blood flow (constriction of arterioles)
What is the effect of adrenaline on vascular tone?
Vasoconstriction in most blood vessels (α1)
Vasodilation in blood vessels of major muscle groups/heart/lungs/liver (β2)
What is the effect of adrenaline on circulating volume?
Increases circulating volume
What is the effect of aldosterone on the renal system?
Increases sodium reabsorption and potassium secretion
What is the effect of aldosterone on circulating volume?
Increases circulating volume
What is the stimulus for renin release from the kidney?
Decrease in renal perfusion, sensed by juxtaglomerular apparatus
What is the role of renin in the RAA axis?
Converts angiotensinogen to angiotensin I
Which enzyme converts angiotensin I to angiotensin II? Mainly where?
ACE (Angiotensin-converting enzyme)
In the vascular endothelium of the lungs and kidneys
What are the 5 main actions of angiotensin II?
- (Overall) Increased sympathetic activity
- (Kidney tubule) NaCl reabsorption, K+ excretion, water retention
- (Adrenals) Aldosterone secretion
- (Arteries) Vasconstriction
- (Pituitary) ADH secretion
What receptor type and pathway does ADH act on in the collecting duct?
V2 receptors
Gs-coupled GPCR –> increases cAMP –> PKA activation
What is the effect of ADH activation of V2 receptors?
Increases the transcription and insertion of aquaporin 2 channels into the apical membrane
What is the effect of ADH on blood flow in the vasa recta?
Vasoconstriction of descending vasa recta
Slows down blood flow to allow more time for water reabsorption
Which receptor and pathway does ADH act on in blood vessels?
V1 receptors
Gq-coupled –> IP3/DAG pathway –> smooth muscle contraction
What is the effect of ADH on circulating volume?
Matintains circulating volume
What is the main angiotensin receptor and its pathway?
AT1
Gq/Gi coupled
Activates PLC –> IP3/DAG pathway
Also inhibits cAMP
Where are AT1 receptors mainly located?
Kidney
Vascular smooth muscle
Cushing’s syndrome involves excess…
cortisol
Conn’s syndrome involves excess…
aldosterone
What are the main physiological characteristics of Conn’s syndrome?
Excessive fluid retention
Hypokalaemia
Hypertension
What are the main physiological characteristics of Cushing’s syndrome?
Hypertension
Increased urination
Hypokalaemia
Hypernatremia
