Intro to the RAAS

Question 1

Hypovolemia stimulates renin release via 3 inputs

Answer 1

Renal sympathetic activation
Intrarenal baroreceptors
Macula densa

Question 2

Non-ACE pathways that convert AI to AII

Answer 2

Chymase: produces in the heart and vascular tissues
Cathepsins
These both have a limited role under physiologic conditions

Question 3

AT1 vs AT2 receptors

Answer 3

Both Angiotensin II receptors
AT1 receptors mediate most effects classically associated with RAAS
AT2 opposes it

Question 4

Effects of AT1 receptor (fast pressor response, slow pressor response, adverse malformation response)

Answer 4

Fast: Vasoconstriction
Slow: Na/H2O retention, thirst
Adverse: Cardiac hypertrophy, platelet thrombosis, insulin resistance, inflammation

Question 5

Aldosterone: what is it made from, where

Answer 5

It is a mineralcorticoid from cholesterol

Primarily in the zona glomerulosa adrenal cortex

Question 6

Aldosterone: what stimulates its release, what inhibits

Answer 6

Release is stimulated by AII and AIII, ADH, endothelin

Inhibited by ANP, dopamine

Question 7

Actions of Aldosterone

Answer 7

Na and H2O reabsorption in the kidney
K and H excretion in the kidney
Na and H2O reabsorption from gut, salivary glands, sweat glands

Question 8

How does the RAAS system cause vasoconstriction?

Answer 8

Angiotensin II (AT1 receptor - increases intracellular Ca causing vasoconstriction)
SNS activation (AII mediated - increase NE release, decrease NE reuptake)

Question 9

Are afferent or efferent arterioles more sensitive?

Answer 9

Efferent (low dose of AII causes constriction, high dose is needed to constrict afferent vessels)

Question 10

Aldosterone effects what channels in the kidney?

Answer 10

Upregulates Na/K exchange pump on basal membrane of principal cells
Upregulates ENaC
Stimulates H secretion via H/K exchange in intercalated cells of cortical collecting tubule

Question 11

4 non-electrolyte effects of aldosterone

Answer 11

Volume (Na retention)
Ischemia (decrease arterial compliance, endothelial dysfunction)
Remodelling (hypertrophy, fibrosis)
Arrhythmia (decrease K and Mg, decrease NOR reuptake)

Question 12

ACE2

Answer 12

Homolog of ACE
Key protective pathway
Opposes AII effects
Widely expressed on multiple organs
Converts AI to Ang1-7

Question 13

Effects of AT2/MAS receptor activation by Ang1-7

Answer 13

Vasodilation
Natriuresis and diuresis
Antifibrosis
Anti-inflammation

Question 14

Bradykinin

Answer 14

Causes same beneficial effects as the AT2 receptor

But gets broken down by ACE

Question 15

Side effects of ACEIs

Answer 15

Cough (increased bradykinin)
Renal impairment
Hyperkalemia (aldosterone antagonists)
Hypotension
Angioedema (rare)
Teratogenicity

Question 16

Contraindications to starting ACEIs

Answer 16

Serum K > 5.0 mmol/L
Serum creatinine > 200 micro mol/L
Critical aortic stenosis
Bilateral renal artery stenosis
History of angioedema