Where is Aldosterone made/released from? What does it bind to?
Aldosterone is made in the cortex of the adrenal gland. Binds to mineralcorticoid receptors (unspecific receptor but can undergo adaptations to make them specific.
What stimulates increased production/release of Aldosterone?
- Angiotensin II
- K+ (powerful, only takes small fluctuations)
What happens when Aldosterone binds to the mineralcorticoid receptor?
It stimulates the ENac (Na+ epithelial channel that drives Na+ reabsorbtion). Reabsorbed Na+ enters capillaries via Na+/K+ ATPase, thereofre also driving K+ excretion.
Increased Na+ and water reabsorbtion, and increased K+ excretion
Main drug to stop aldosterones effects? Why do we have this drug?
Spiranolactone is the main drug, blocks Mineralcorticoid receptor.
Treats Hyperaldosteronism that may represent 10% cases of Hypertension.
**also amiloride also blocks ENac
In some cases, you can do an xray of the renal arteries and clearly see it's renal vascular hypertension (and put in a stent) But in other cases, you can't, how big of a diameter reduction do you need before you can classify it??
Small diameter decrease not enough to be renal HT but enough to increase angiotensin II
Survival rates for those with heartfailure on the best reccomended drug out there?
50% even with spironolactone. Scary that there is not much out there!
Q) Normally aldosterone stimulates the reabsorption of approx 33g of NaCl/day. If a patient loses 100% of adrenal function, wll 33g of NaCl be excreted per day indefinitely?
No. As soon as the person starts to become Na+ deficient as a result of the increased excretion, the usual Na-retaining reflexes will be set into motion. Although Aldosterone secretion can't be raised, but they can lower GFR and alter other factors that influence the tubular-sodium reabsorption to compensate at least partially for the decreased aldosterone-dependent Na+ absorption.
Not as ideal, but liveable!
What regulates Osmolality
Regulated by changes in renal water handling (ADH)
- Tightly regulated to 1-2%
What regulates ECF volume?
Regulated by changes in Renal Na+ handling
- Varies up and down constantly
- Mediators: Renin-angiotensin, SNS
WHy does ECF osmolality need to stay constant?
Because this controls changes in volume! Some cells are very vunerable/sensitive to these changes!
Changes in ECF volume are compensated by ...
How is this done?
changes in Na+ reabsorption by the kidney.
Eg) Decreased ECF volume is compensated by increased renal absorption of Na+. When ECF volume increases, vice versa.
ANP, what is it and how is it released?
Atrial Natriuretic peptide(28aa), inhibits Na+ reabsorption
- Released from atria in response to increased filling pressure and increased atrial sretch
- ANP binds to receptors → increased cGMP
Actions of ANP
Decreases Na+ reabsorption in DT and outer medullary CT by blocking ENac and by inhibiting Na/K- ATPase
Inhibits aldosterone release
Inhibits renin release
Vasodilates afferent arteriole to increase GFR
What happens when you eat salty chips? Flow Diagram.
What does an increase in Plasma and central Na+ levels to RSNA??
Decrease in sympathetic drive to the kidney. Affects angiotensin II and directly on GFR (symp. nerves affect afferent more then efferent)