Wk6 Pathophysiology of renin-angiotensin-aldosteron system

Question 1

Where does renin come from?

Answer 1

Kidney; Juxtaglomerular cells; secreted by granular cells

Question 2

What is the rate limiting step of the production of angiotensin II?

Answer 2

Renin secretion from the kidney

Question 3

Where does aldosterone come from?

Answer 3

Adrenal gland

Question 4

What is reninoma?

Answer 4

Very rare tumor of the justaglomerular apparatus.

Question 5

What hormone is responsible for salt and water retention?

Answer 5

Aldosterone

Question 6

What type of enzyme is renin?

Answer 6

protolytic enzyme

Question 7

What are the major regulators of renin secretion? (3)

Answer 7

1) Activation of sympathetic nerves (B1-adrenoceptors)
2) reduced renal arterial pressure (reduced MAP)
3) decreased sodium concentration in distal tubules

Question 8

What do the macula densa cells do? Where are they located?

Answer 8

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.

Question 9

What do macula densa cells do if they detect low sodium concentration?

Answer 9

They will secrete renin, which will act to increase volume/MAP.

Question 10

What does angiotensin II do?

Answer 10

1) constrict systemic arterioles –> increase TPR

2) acts on adrenal cortex to secrete aldosterone

Question 11

What does aldosterone do?

Answer 11

Increases sodium and water reabsorbtion by kidney

Question 12

Where is angiotensinogen produced?

Answer 12

liver

Question 13

What are the receptors on smooth muscle that antiogensin II act on?

Answer 13

AT1 receptors

causes vasocontriction

Question 14

What are the fast, slow, and structural responses of angiotensin II on the cardiovascular system?

Answer 14

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

Question 15

What would the blood pressure be in a ACE knockout mouse?

Answer 15

very low blood pressure

Question 16

What are the negative feedback loops reducing renin secretion?

Answer 16

• Angiotensin II
• Sodium retention
• increased blood pressure

Question 17

What is renovascular hypertension?

Answer 17

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

Question 18

AT1-receptor antagonists

Answer 18

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

Question 19

In renovascular hypertension, why are ACE inhibitors not always the best treatment?

Answer 19

Because it will reduce the glomerular filtration rate and cause renal failure

Question 20

Where is aldosterone produced?

Answer 20

adrenal cortex.

Question 21

What is produced in the adrenal medulle?

Answer 21

adrenaline and noradrenaline

Question 22

Mineralcorticoids
Where made?
Most common examples?
Actions?
Regulation?

Answer 22

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

Question 23

How does angiotesin II stimulate aldosterone secretion? molecular level…

Answer 23

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.