RAAS system

Question 1

where is renin synthesised stored and released from

Answer 1

juxtaglomarular cells (in kidneys) aka renin releasing granular cells

Question 2

what is the precursor molecule for renin

Answer 2

prorenin

Question 3

what enzymes convert prorenin to renin (2)

Answer 3

proteolytic enzymes -> cathepsin B & D

Question 4

what is the function of renin

Answer 4

conversion of angiotensinogen -> angiotenin I

Question 5

RAAS pathway steps

Answer 5

angiotensinogen –(renin)–> angiotensin I –(ACE)–> angiotensin II -> angiotensin III

Question 6

what increases renin release (4)

Answer 6

1. decreased arterial BP
2. decreased BP in glomerular vessels (afferent arterioles)
3. increased loss of Na+ / water (i.e. less Na+ in DCT)
4. increased sympathetic activity (fight or flight to increase BP)

Question 6

what is the active form of angiotensinogen

Answer 6

angiotensin II

Question 6

what decreases renin release (3)

Answer 6

1. Na+ / water retention
2. increased BP
3. activation of AT1 receptors (short negative feedback loop)

Question 7

what 3 pathway cotnrol renin secretion

Answer 7

1. macular densa
2. intrarenal baroreceptor pathway
3. beta 1-receptor pathway

Question 8

what is the macular densa pathway of renin control

Answer 8

1. reabsorption of NaCl occurs at the macula densa
2. increase in NaCl flux causes inhibition of renin release from the juxtaglomerular cells and vice versa
3. ATP, adenosine and prostaglandins modulate this pathway

Question 9

what common drug class can affect the macula densa pathway of renin release and why

Answer 9

NSAIDs -> inhibit PGE release which reduces renin release via the macula densa pathway

Question 10

where is the macula densa situated

Answer 10

on the thick ascending limb/ distal tubule -> loops round so it is in contact w the afferent and efferent arterioles

Question 11

what does the juxtaglomerular apparatus consist of (3)

Answer 11

1. macula densa
2. granular cells
3. mesangium extra glomerular cells

Question 12

what channel is responsible for the NaCl absorption by the macula densa

Answer 12

Na+/K+/2Cl- symporter

NaCl and K+ into the macula densa cells

Question 13

what is the channel responsible for the removal of Na+ from the macula densa

Answer 13

Na+/K+ ATPase

Question 14

how is adenosine produced to modulate the juxtaglomerular cell release of renin

Answer 14

via the Na+/K+ATPase which results in the byproduction of ADP which is then further broken down into adenosine

i.e. higher NaCl reabsorbtion in to the macula densa = increased adenosine produciton = inhibition of renin for JG cell

Question 15

what is macula densa regulation usually based on the concentration of

Answer 15

[Cl-] -> rather than [Na+] as the [Na+] in the tubular lumen is usually higher than required for saturating the symporter and so changes in Na+ conc usually don’t have an effect as the symporter will remain saturated

Question 16

what is the intrarenal baroreceptor pathway

Answer 16

1. increase in BP or renal perfusion pressure in preglomerular vessles
2. inhibition of renin release via beta1 receptors on juxtaglomerular cells

i.e. increased BP = descreased renin and vice versa

Question 17

what is the short loop -ve feedback mechanism seen in the RAAS system

Answer 17

increase in renin secretion -> increased angiotensin II-> AT1 on JG cells -> decreased renin

Question 18

what factors affect the long loop negative feedback mechanism (3)

Answer 18

1. activation of high pressure baroreceptors
2. increased renal arterial pressure in the preglomerular vessels
3. reduced NaCl absoprtion from the proximal tubule
   -> reduction in renin release

Question 19

phsyiological factors modifying renin release (3)

Answer 19

1. systemic BP
2. dietary salt intake
3. pharmacological agentsw

Question 20

what drugs can modify renin release

Answer 20

1. NSAIDs -> inhibit PG synthesis
2. loop diuretics - decrease BP and increased NaCl reabsoption (so less NaCl to stimulate macula densa in the distal tubule) causing increased renin release
3. ACEi
4. ARBs
5. renin inhibitors
6. BBs -> decrease renin by reducing Beta receptor activation

Question 21

what is angiotensin I converting enzyme

Answer 21

a glycoprotein, non-specific enzyme that is identical to kinsae II -> inactivates bradykinin and other potent vasodilators

converts angiotensin I -> angiotensins II

Question 22

when does the RAAS system become ativated

Answer 22

decrease in blood volume or blood pressure

Question 23

what kind of receptors are juxtaglomerular cells

Answer 23

baroreceptors - detect drop in blood pressure in afferent arterioles

Question 24

where is Na+ resorbed

Answer 24

1. proximal convoluted tubule (65%) 2. loop of henle (13%) 3. distal convoluted tubule (5%)

Question 25

why does lower BP result in increased Na+ resorption and what does this mean for renin release

Answer 25

blood moves slower through the nephron if BP is lower => there is more time for Na+ to be reabsorbed so more resorption occurs -> increased renin release as less Na+ detected at macula densa

Question 26

what organ produces angiotensinogen

Answer 26

liver

Question 27

what organs produce ACE (2)

Answer 27

lungs and kidneys

Question 28

actions of angiotensin II (6) !!

Answer 28

1. systemic vascoconstriction (increases BP) 2. constricts efferent arterioles (increased GFR, increased Na+ in DCT) 3. aldosterone release -> results in resorption of Na+ in DCT and excretion of K+(and thus water follows resulting in increased BP) 4. travels to pit gland and stimulates post. pit to release ADH (water reabsorbed in the collecting duct) 5. inhibits renin release (increased tubular NaCl resorption which leads to decreased renin release) 6. increased sympathetica activity

Question 29

what is ACE2

Answer 29

an enzyme that acts as a counter balance to ACE -> turns Ang II back into Ang I

Question 30

what is Ang II converted into

Answer 30

Angiotensin III (by aminopeptidase A)

Question 31

function of angiotensin III

Answer 31

central regulation of hypertension and ADH release

Question 32

where does ADH cause resorption of water from (2)

Answer 32

1. DCT 2. collecting duct

Question 33

how can Ang I be converted to Ang II without ACE

Answer 33

alternate pathway enzymes e.g. cathepsin, tonin, heart chymase

Question 34

what is a rapid pressor response

Answer 34

an increase in systolic blood pressure (SBP) of at least 30 mmHg above the baseline or placebo measurements

Question 35

what is the slow pressor response

Answer 35

prolonged infusions of angiotensin II (AngII) entails a delayed rise in BP

Question 36

what channel is blocked by furosemide

Answer 36

Na+/K+/2Cl- cotransporter in the thick ascending limb of the loop of Hen

Question 37

how does aldosterone affect the cardiovascular systme (6)

Answer 37

1. vascular sm cells hypertrophy and proliferation 2. increased extracellular matric of vascular sm cells 3. hypertrophy of cardiac myocytes 4. increased extracellular matrix production by cardiac myofibroblasts 5. increased cardiac contractility (opens VG gated Ca2+ channels) 6. increased cardiac rate (central symapthetic tone)

Question 38

inhibitors of the RAAS system (drug classes - 3)

Answer 38

1. ACEi 2. ARBs 3. direct renin inhibitors

Question 39

what layer of the adrenal gland is aldosterone released from

Answer 39

glomerulosa