2-3 Renin Angiotensin Aldosterone System

Front 1

Control of renin release

Back 1

1) Decreased afferent arteriolar perfusion pressure --> stimulates release

2) B1 adrenergic receptors --> stimulates release

3) Decrease salt delivery to macula densa (distal tubule) --> stimultes release

4) Angiotensin II --> direct feedback inhibition

Front 2

What happens when there is too much NaCl flowing by the macula densa?

Back 2

Adenosine is released --> constriction of afferent arteriole --> decreased GFR

Renin reduction will also be decreased (mostly a systemic effect)

Front 3

RAA Axis

Back 3

1) Renin converts angiotensinogen to ang I (rate controlling step is produciton/release of renin)

2) Ang I --> Ang II via ACE

3) Angiotensin II stimulates aldosterone secretion --> leads to increased sodium and water retention + increased preload

4) Angiotensin II also stimulates constriction of vascular smooth muscle --> increased afterload

Front 4

What happens if you continuously infuse angiotensin II?

Back 4

Blood pressure will continue to increase up until a certain point -- ang II will feedback negatively on renin and cause the blood pressure to plateau/decrease

Front 5

What happens if there is a decrease in blood volume or blood pressure?

Back 5

1) Juxtaglomerular cells of kidneys sense the decrease in blood pressure

2) Secretion of renin --> RAA axis

3) Angiotensin II leads to vasoconstriction of arteries which causes an increase in BP

4) Ang II also stimulates aldosterone secretion (along with increased K+ in ECF)

5) Aldosterone leads to increased Na + water reabsorption in the kidney and increased secretion of K+/H+ ions into urine --> inc blood volume --> inc blood pressure

Front 6

Stimuli that indicate decrease in blood volume/pressure?

Back 6

Dehydration, Na+ deficiency, or hemorrhage

Front 7

Glomerular effects of angiotensin II

Back 7

-Ang II mediates vasoconstriction of the efferent arteriole

-This helps maintain adequate intraglomerular pressure for transcapillary glomerular perfusion

Front 8

Proximal tubular effects of angiotensin II

Back 8

-Causes constriction of efferent arteriole

-Leads to increased glomerular blood pressure and filtration and reduces BP in peritubular capillary

-Reduces resistance to tubular reabsorption

-Tubular reabsorption increases (increases proximal tubular Na+ absorption)e

-Urine volume is less but concentration is high

Front 9

Acute and chronic effects of angiotensin II systemically

Back 9

-Sympathetic nervous system activation

-Blood vessel vasoconstriction, remodeling, endothelin release, atherosclerosis

-Heart hypertrophy, LV remodeling, fibrosis

-Aldosterone secretion

-Kidney: sodium retention, glomerular filtration, proteinuria

Front 10

What is cleaved to go from Ang I --> Ang II?

Back 10

ACE removes His-Leu residue from the end of Ang I

Front 11

Where can ACE2 cleave?

Back 11

-ACE2 will cleave just the Leu residue off of Ang I which forms Ang 1-9

-ACE2 will cleave just the Phe residue off of Ang II

which forms Ang 1-7

Front 12

what does ACE do to Ang 1-9?

Back 12

Cleaves a Ph-His residue off to form Ang 1-7 (vasodilator)

Front 13

Effects of angiotensin II? Ang 1-7?

Back 13

Ang II = vasoconstrictor

Ang 1-7 = vasodilator (main product of ACE2)

Front 14

Effects of angiotensin II vs angiotensin 1-7

Back 14

-Ang II binds to AT1 receptor --> vasoconstriction, endothelial dysfunction, proliferation/hypertrophy, fibrosis, atherosclerosis, thrombosis, arrhythmogenesis

-Ang 1-7 binds to Mas receptor --> vasodilation, increased endothelial function, antiproliferation, decreased hypertrophy, dec fibrosis, dec thrombosis, antiarrhythmic

Front 15

Inhibitors of the RAAS System

Back 15

-Renin inhibitors inhibit conversion of Angiotensinogen --> Ang I (ex - aliskiren)

-ACE inhibitors inhibit conversion of Ang I to Ang II (as well as the breakdown of bradykinin)

-ARBs inhibit angiotensin II binding to AT1

Front 16

ARB effects on AT1 vs AT2 receptors

Back 16

-AT1 receptors are inhibited by ARBs - this inhibits: vasoconstriction, SNS activation, increased aldosterone, increased vasopression, increased oxid stress, negative feedback for renin release

-AT2 receptors are stimulated by ARBs - this stimulates vasodilation, apoptosis, antiproliferation, increased bradykinin, NO release

Front 17

Effect locations for drugs that block the RAAS

Back 17

-Renin blockers/impaired release of renin

-ACE inhibitors

-ARBs

-Impaired aldosterone metabolism

-Aldosterone receptor blockers

-Sodium channel blockers (block reuptake induced by aldosterone)

Front 18

Location of aldosterone receptors

Back 18

-Kidneys

-Brain

-Arteries

-Heart

Front 19

Why do ACE inhibitors cause cough?

Back 19

Decreased breakdown of bradykinin, which can lead to cough reflex

Front 20

What does aldosterone blockade do to urinary excretion of albumin?

Back 20

Aldosterone blockade decreases urinary albumin excretion rate (decreases proteinuria)

Front 21

Aldosterone blockade + cardiac mortality?

Back 21

Decreased cardiac mortality compared to placebo

Front 22

Type IV renal tubular acidosis

Back 22

-Hyperkalemic, hyperchloremic, metabolic acidosis

-Not a tubular defect

-Caused by aldosterone resistance or deficiency - most often present in cases of diabetic nephropathy or interstitial nephritis with mild/moderate renal insufficiency

-Relative hypoaldosteronism leads to impaired secretion of K+ and H+ by collecting tubule, causing hyperkalemia + acidosis

-Hyperkalemia impairs proximal tubular production of ammonia - urine pH is appropriately low but the amount of buffer (NH4+) is reduced

Front 23

Causes of hypokalemia

Back 23

-Decreased intake

-Shift into cells: metabolic alkalosis, insulin

-Renal loss: excess aldosterone, diuretics, renal tubular acidosis, Batter's syndrome, hypomagnesemia

Front 24

Causes of hyperkalemia

Back 24

-Decreased excretion: renal failure, aldosterone resistance, aldosterone deficiency

-Shift out of cells: metabolic acidosis, digoxin, beta blockers, lack of insulin

Front 25

How does hypo/hyperkalemia affect RMP of cells?

Back 25

If you are hyperkalemic, less K+ will come out of cells (hypopolarization)

If you are hypokalemic, more K+ will leave cells (hyperpolarization)

Front 26

How does hypo/hypercalcemia affect RMP of cells?

Back 26

Hypercalcemia = more depolarized

Hypocalemia = more hyperpolarized

Front 27

What happens if you have hypocalcemia + hyperkalemia?

Back 27

Your resting membrane potential and threshold potential are very close --> cells are extremely easy to excite

Front 28

To distinguish primary aldosterone deficiency from other causes of hyperkalemia, get a ____

Back 28

plasma renin activity level

Front 29

To distinguish renal from GI losses as a cause of hypokalemia, use the _____

Back 29

Transtubular K+ gradient (TTK):

TTK = [K+]urine x osmolality(blood)/[K+] blood x osmolality(urine)

TTK <4 in presence of hypokalemia, >6 in presence of hyperkalemia