Renin-Angiotensin-Aldosterone System

Question 1

What does the renin-angiotensin-aldosterone system control?

Answer 1

arterial BP, extracellular volume, sodium homeostasis, and tissue perfusion

Question 2

What are the 3 body fluid compartments?

Answer 2

1. intracellular fluid
2. interstitial extracellular fluid
3. plasma extracellular fluid

Question 3

What 3 organs regulated volume status?

Answer 3

1. brain= center for gauging osmolality via the hypothalamus at the osmoreceptors= release of ADH from pituitary.
2. kidney
3. heart

Question 4

How do we regulate our volume status?

Answer 4

by either modifying extracellular volume or controlling osmolality (solute concentration).

Question 5

How do we maintain BP?

Answer 5

CO x TPR

Question 6

What is the center of the RAAS?

Answer 6

the kidney via its production of renin

Question 7

**How does renin act when BP is low?

Answer 7

it converts angiotensinogen (large protein produced in the liver that circulates in the blood), to a smaller protein angiotensin I. Angiotensin converting enzyme (ACE) produced in the lungs and found on both the surfaces of pulmonary and renal endothelium, then converts angiotensin I to the active form angiotensin II.
Angiotensin II then:
1. increases sympathetic activity
2. stimulates tubular Na+ and Cl- reabsorption (and thus water), and K+ secretion.
3. stimulates the adrenal cortex to secrete aldosterone, thus increasing tubular Na+ and Cl- reabsorption (and thus water), and K+ secretion.
4. arteriolar vasoconstriction (increasing BP)
5. pituitary gland ADH secretion (increasing H2O absorption at collecting duct).

Question 8

What senses the amount of Na+ in the tubular filtrate?

Answer 8

macula densa cells in the DCT

Question 9

**What are the 4 independent factors that affect renin release from the JGA?

Answer 9

1. renal baroreceptor in the afferent arteriole
2. delivery of NaCl (sensed as changes in Cl- at the macula densa)
3. sympathetic stimulation (B1 receptors)
4. negative feedback of angiotensin II (decreasing renin release).

Question 10

What is the Goldblatt kidney?

Answer 10

experimental modeling showing the effects of renin release and its relationship to volume and blood pressure when clipping one of 2 kidneys, or one kidney with one whole kidney removed.

Question 11

What were the results of the Goldblatt experiment?

Answer 11

• 2 kidneys with 1 clipped= high BP, due to high renin, but normal volume (bc the other kidney can handle the volume overload).
• 1 kidney with 1 clipped= high BP, and high volume, but low renin (due to negative feedback of high angiotensin II on renin production).

Question 12

What angiotensin II receptor is responsible for vasoconstriction?

Answer 12

AT-1 receptor

Question 13

**What does angiotensin II do the the afferent and efferent arterioles, respectively?

Answer 13

constricts both vessels, but MORE on the EFFERENT arteriole, thus increasing GFR.

Question 14

What happens when right atrial pressure increases due to increased blood volume?

Answer 14

the stretch of the right atrium causes the release of ANP, which acts to decrease the release of renin, and thus lower angiotensin II, decreasing overall BP.

Question 15

What negative effects can excess angiotensin II do the the cardiovascular system?

Answer 15

cardiac remodeling, collagen deposition in myocardial tissue, fibrosis, and contributes to and maintains LVH :(

Question 16

What is the precursor for the mineralocorticoid aldosterone?

Answer 16

cholesterol (just like cortisol), and is made in the zona glomerulosa of the adrenal cortex.

Question 17

What specific cells does aldosterone affect to increase BP?

Answer 17

the principle cells of the DCT/CT/CD, and binds to a cytoplasmic mineralocorticoid receptor, which then enters the nucleus to increase transcription of ENac, to increase Na+ reabsorption (and thus water). In order to remain electrochemically balanced, K+ is secreted in exchange for Na+.

Question 18

So, are angiotensin II and serum K+, major regulators of aldosterone?

Answer 18

YES

Question 19

Does aldosterone also have functions on the colon and sweat glands?

Answer 19

yes

Question 20

If you eat a lot of salt throughout the day, will you increase or decrease the RAAS system?

Answer 20

decrease

Question 21

** Will aldosterone increase or decrease with excess K+ (hyperkalemia)?

Answer 21

INCREASE in order to increase the amount of K+ secretion and thus excretion via the absorption of Na+ (since K+ will leave in order to maintain the balance of charge).

Question 22

What are the 4 big pathologies associated with RAAS?

Answer 22

1. HTN
2. CVD
3. kidney disease
4. DM

Question 23

What is the difference between primary (essential) and secondary HTN?

Answer 23

• primary= idiopathic (we don’t know what’s causing it). Thus renin would be normal or low in these pts. MOST pts.
• secondary= identifiable underlying secondary cause.

Question 24

What drug do we use to treat HTN, DM, heart failure, and kidney damage reduction?

Answer 24

ACE inhibitors or ARBs. This will decrease the GFR, bc you are preventing the constriction of the efferent arteriole.

Question 25

** What pathology is easily treated but easily missed in evaluation of younger people (40s) with HTN?

Answer 25

renal artery stenosis. Simply stent it to correct the problem.

Question 26

** What pathology could cause HTN, low serum K+, elevated aldosterone, and low renin levels?

Answer 26

aldosterone producing adenoma= thus explaining the BP (salt water retention), and hypokalemia (bc you are dumping K+ in exchange for Na+ reabsorption). You will not see edema however, due to “aldosterone escape” (the body adjusts to the increase in salt and water retention).
*Treat with K+ sparing diuretic (spironolactone)