RAAS system Flashcards
where is renin synthesised stored and released from
juxtaglomarular cells (in kidneys) aka renin releasing granular cells
what is the precursor molecule for renin
prorenin
what enzymes convert prorenin to renin (2)
proteolytic enzymes -> cathepsin B & D
what is the function of renin
conversion of angiotensinogen -> angiotenin I
RAAS pathway steps
angiotensinogen –(renin)–> angiotensin I –(ACE)–> angiotensin II -> angiotensin III
what increases renin release (4)
- decreased arterial BP
- decreased BP in glomerular vessels (afferent arterioles)
- increased loss of Na+ / water (i.e. less Na+ in DCT)
- increased sympathetic activity (fight or flight to increase BP)
what is the active form of angiotensinogen
angiotensin II
what decreases renin release (3)
- Na+ / water retention
- increased BP
- activation of AT1 receptors (short negative feedback loop)
what 3 pathway cotnrol renin secretion
- macular densa
- intrarenal baroreceptor pathway
- beta 1-receptor pathway
what is the macular densa pathway of renin control
- reabsorption of NaCl occurs at the macula densa
- increase in NaCl flux causes inhibition of renin release from the juxtaglomerular cells and vice versa
- ATP, adenosine and prostaglandins modulate this pathway
what common drug class can affect the macula densa pathway of renin release and why
NSAIDs -> inhibit PGE release which reduces renin release via the macula densa pathway
where is the macula densa situated
on the thick ascending limb/ distal tubule -> loops round so it is in contact w the afferent and efferent arterioles
what does the juxtaglomerular apparatus consist of (3)
- macula densa
- granular cells
- mesangium extra glomerular cells
what channel is responsible for the NaCl absorption by the macula densa
Na+/K+/2Cl- symporter
NaCl and K+ into the macula densa cells
what is the channel responsible for the removal of Na+ from the macula densa
Na+/K+ ATPase
how is adenosine produced to modulate the juxtaglomerular cell release of renin
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
what is macula densa regulation usually based on the concentration of
[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
what is the intrarenal baroreceptor pathway
- increase in BP or renal perfusion pressure in preglomerular vessles
- inhibition of renin release via beta1 receptors on juxtaglomerular cells
i.e. increased BP = descreased renin and vice versa
what is the short loop -ve feedback mechanism seen in the RAAS system
increase in renin secretion -> increased angiotensin II-> AT1 on JG cells -> decreased renin
what factors affect the long loop negative feedback mechanism (3)
- activation of high pressure baroreceptors
- increased renal arterial pressure in the preglomerular vessels
- reduced NaCl absoprtion from the proximal tubule
-> reduction in renin release
phsyiological factors modifying renin release (3)
- systemic BP
- dietary salt intake
- pharmacological agentsw
what drugs can modify renin release
- NSAIDs -> inhibit PG synthesis
- loop diuretics - decrease BP and increased NaCl reabsoption (so less NaCl to stimulate macula densa in the distal tubule) causing increased renin release
- ACEi
- ARBs
- renin inhibitors
- BBs -> decrease renin by reducing Beta receptor activation
what is angiotensin I converting enzyme
a glycoprotein, non-specific enzyme that is identical to kinsae II -> inactivates bradykinin and other potent vasodilators
converts angiotensin I -> angiotensins II
when does the RAAS system become ativated
decrease in blood volume or blood pressure
what kind of receptors are juxtaglomerular cells
baroreceptors - detect drop in blood pressure in afferent arterioles
where is Na+ resorbed
- proximal convoluted tubule (65%)
- loop of henle (13%)
- distal convoluted tubule (5%)
why does lower BP result in increased Na+ resorption and what does this mean for renin release
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
what organ produces angiotensinogen
liver
what organs produce ACE (2)
lungs and kidneys
actions of angiotensin II (6) !!
- systemic vascoconstriction (increases BP)
- constricts efferent arterioles (increased GFR, increased Na+ in DCT)
- aldosterone release -> results in resorption of Na+ in DCT and excretion of K+(and thus water follows resulting in increased BP)
- travels to pit gland and stimulates post. pit to release ADH (water reabsorbed in the collecting duct)
- inhibits renin release (increased tubular NaCl resorption which leads to decreased renin release)
- increased sympathetica activity
what is ACE2
an enzyme that acts as a counter balance to ACE -> turns Ang II back into Ang I
what is Ang II converted into
Angiotensin III (by aminopeptidase A)
function of angiotensin III
central regulation of hypertension and ADH release
where does ADH cause resorption of water from (2)
- DCT
- collecting duct
how can Ang I be converted to Ang II without ACE
alternate pathway enzymes e.g. cathepsin, tonin, heart chymase
what is a rapid pressor response
an increase in systolic blood pressure (SBP) of at least 30 mmHg above the baseline or placebo measurements
what is the slow pressor response
prolonged infusions of angiotensin II (AngII) entails a delayed rise in BP
what channel is blocked by furosemide
Na+/K+/2Cl- cotransporter in the thick ascending limb of the loop of Hen
how does aldosterone affect the cardiovascular systme (6)
- vascular sm cells hypertrophy and proliferation
- increased extracellular matric of vascular sm cells
- hypertrophy of cardiac myocytes
- increased extracellular matrix production by cardiac myofibroblasts
- increased cardiac contractility (opens VG gated Ca2+ channels)
- increased cardiac rate (central symapthetic tone)
inhibitors of the RAAS system (drug classes - 3)
- ACEi
- ARBs
- direct renin inhibitors
what layer of the adrenal gland is aldosterone released from
glomerulosa
