Wk6 Pathophysiology of renin-angiotensin-aldosteron system Flashcards
Where does renin come from?
Kidney; Juxtaglomerular cells; secreted by granular cells
What is the rate limiting step of the production of angiotensin II?
Renin secretion from the kidney
Where does aldosterone come from?
Adrenal gland
What is reninoma?
Very rare tumor of the justaglomerular apparatus.
What hormone is responsible for salt and water retention?
Aldosterone
What type of enzyme is renin?
protolytic enzyme
What are the major regulators of renin secretion? (3)
1) Activation of sympathetic nerves (B1-adrenoceptors)
2) reduced renal arterial pressure (reduced MAP)
3) decreased sodium concentration in distal tubules
What do the macula densa cells do? Where are they located?
They are located betwene the afferent arteriole, efferent artiole and the distal tubule (it wraps back around)
They monitor the NaCl concentration in the distal tubule.
What do macula densa cells do if they detect low sodium concentration?
They will secrete renin, which will act to increase volume/MAP.
What does angiotensin II do?
1) constrict systemic arterioles –> increase TPR
2) acts on adrenal cortex to secrete aldosterone
What does aldosterone do?
Increases sodium and water reabsorbtion by kidney
Where is angiotensinogen produced?
liver
What are the receptors on smooth muscle that antiogensin II act on?
AT1 receptors
causes vasocontriction
What are the fast, slow, and structural responses of angiotensin II on the cardiovascular system?
FAST
- vasocontriction via AT1 receptors
- sensitizes smooth muscle to catecholamines
SLOW
- increased aldosterone secretion from the adrenal gland
- increased sodium reabsorption via proximal tubule
- altered renal hemodynamics (arteriolar resistance)
STRUCTURAL
- vascular and cardia hypertrophy and remodeling (in response to hypertension)
- cell growth stimulation
- increased afterload
What would the blood pressure be in a ACE knockout mouse?
very low blood pressure
What are the negative feedback loops reducing renin secretion?
- Angiotensin II
- Sodium retention
- increased blood pressure
What is renovascular hypertension?
Just means there is a known cause for high BP and its renal and vascular in nature. Usually the problem is stenosis that results in renal ischemia.
Renal ischemia –> renin secretion –> higher blood pressure
AT1-receptor antagonists
non-peptide competitive inhibitors of AT1
they block the ability of angiotensins II and III to stimulate pressor and cell proliferative effects
- antihypertensive effects
- cell growth effects
- lack “bradykinin” effects
In renovascular hypertension, why are ACE inhibitors not always the best treatment?
Because it will reduce the glomerular filtration rate and cause renal failure
Where is aldosterone produced?
adrenal cortex.
What is produced in the adrenal medulle?
adrenaline and noradrenaline
Mineralcorticoids Where made? Most common examples? Actions? Regulation?
All steroid hormones are produced in the liver.
Aldosterone makes up for 90% os mineralcorticoid activity
10% DOC, corticosterone, cortisol
Actions:
- increase sodium reabsoprtion and potassium excretion
- increased extracellular volume
Regulators:
- potassium direct stimulation of aldosterone secretion by adrenal cortex
- ACTH
- sodium concentration
- ANP –> decreases
How does angiotesin II stimulate aldosterone secretion? molecular level…
Angiotensin II binds to the AT1 receptor. This stimulates a pathway which eventually causes cholesterol uptake into the mitochonria, which stimulates aldosterone secretion from the cell.
