L44 – Roles of atrial stretch receptors, renin-angiotensin-aldosterone system (RAAS) and atrionatriuretic peptides (ANP) in the regulation of body compartment fluids Flashcards Preview

MBBS I CPRS > L44 – Roles of atrial stretch receptors, renin-angiotensin-aldosterone system (RAAS) and atrionatriuretic peptides (ANP) in the regulation of body compartment fluids > Flashcards

Flashcards in L44 – Roles of atrial stretch receptors, renin-angiotensin-aldosterone system (RAAS) and atrionatriuretic peptides (ANP) in the regulation of body compartment fluids Deck (84):

What does the RAAS regulate?

Coordinates a variety of
physiological processes for proper regulation of blood volume and pressure


3 types of mechanisms for control of blood volume?



Which 2 types of blood volume control mechanisms share a common mechanism for blood volume detection?

Neural and Neurohormonal


Describe sequence of neural control of blood volume?

Receptor > afferent nerve > CNS > efferent nerve > effector organ or tissue


Describe sequence of hormonal control of blood volume?

Detection of change (e.g. atrial muscle stretch) > hormone release > blood circulation > effect on tissues


Describe sequence of neurohormonal control of blood volume?

Receptor > afferent nerve > CNS > hormone release AND efferent nerve > effector organ or tissue


Compare speed of response between 3 types of mechanisms for control of blood vol?

Neural = immediate
Neurohormonal = rapid onset
Hormonal = slow onset


Compare scale of effect between 3 mechanisms in blood vol. control?

Neural = local
Neurohormonal = Globlal
Hormonal = global


Compare duration of effect between 3 mechanisms in blood vol. control?

Nerual = effect disappear immediately
Neurohormonal = Long-lasting
Hormonal = persist for hours


2 reasons for regulating blood volume?

Eliminate excess volume by urine formation> lower BP

Protect CVS from damage by large volume


2 ways blood volume is regulated?

By regulating water excretion and salt excretion


What is altered in regulation of water excretion?

Resorption of water from collecting duct


What alters regulation of salt excretion?

Renin-angiotensin- aldosterone system

Atrial natriuretic peptide (ANP)


How does salt excretion indirectly regulate water excretion?

Water follows salt due to osmotic gradient


What receptors detect rise in blood volume?

Atrial receptors - stretch receptors


Where are atrial receptors located?

Junctions of the vena cava with RA and pulmonary veins with LA


How does increased blood volume cause increased firing of stretch receptors>?

Increased B.V. > increase Venous pressure > increase venous return > increase atrial filling > Stretch atrial wall > more firing


What are the functions of the L/R cardiac sympathetic nerves?

R. sym= regulate HR

L. sym= regulate contractility


What 2 reflexes make up Bainbridge reflex?

Increase R. cardiac sympathetic nerve activity

Decrease Renal sympathetic nerve activity


What other nerves respond in reflex to increased blood volume apart from Bainbridge reflex?

Decreased skeletal muscle and splanchnic circulation sympathetic activity


What is the result of Decreased skeletal muscle and splanchnic circulation sympathetic activity ?

Decrease TPR > prevents large blood volume from increasing blood pressure


How is cardiac output controlled when blood volume is higher?

Increased BV > increase venous return > should increase stroke volume but increased R. cardiac sympathetic nerve activity = increase HR

Increase in HR causes decrease in stroke volume

CO = SV x HR

CO remains higher but under control
Prevent atria overstretch


How is BP related to changes in CO and TPR when blood volume is high? ( think which nerves are activated)

CO is higher (but under control)

Decreased sympathetic activity to splanchnic circulation and skeletal muscles = decrease TPR


Stable BP


In bainbridge reflex. Result of change in renal sympathetic activity on blood volume during high BV?

High BV > Decrease renal sympathetic activity > Allow renal AFFERENT arteriole to dilate > more blood enters capillaries > Increase glomerular capillary hydrostatic pressure > increase GFR > more urine production > lower BV


How do atrial receptors and ADH regulate blood volume?

High B.V. > increase activity of atrial stretch receptor > afferent nerve to CNS > LOWER release of ADH from pituitary gland > less water reabsorption at collecting ducts > more urine production > Lower B.V.


What is Renin and Where is Renin secreted?

proteolytic enzyme: cleaves terminal section from
angiotensinogen to form angiotensin I

secretion from juxtaglomerular (JG) cells in afferent arteriole wall of kidney glomerulus


2 components of juxtaglomerular apparatus?

Juxtaglomerular cells + Macula Densa


What are JG cells' function?

JG cells: release renin, innervated by sympathetic nervous system


How does renin lead to formation of aldosterone ?

Angiotensinogen > (renin) > Angiotensin I > (ACE) > Angiotensin II > (adrenal cortex) > aldosterone


What is ACE? Found where?

Angiotensin converting enzyme

At pulmonary capillary endothelial cell (and PCT)


Where is angiotensinogen made?

Liver (and PCT)


At cellular level, what 2 signals control renin release from JG cells?

cAMP and Ca2+


How do Ca and cAMP control renin release?

Increase intracellular cAMP = stimulate renin release

Decrease intracellular Ca = inhibit renin release


How does increase intracellular Ca cause decrease renin release?

Increase intracellular Ca = inhibit adenyl cyclase 5 > inhibit formation of cAMP from ATP > lower intracellular cAMP conc. > less release of renin through PKC/ other ion channels


Why is calcium's role in renin regulation odd?

Only in kidney where increase calcium conc. doesnt lead to release of granules


What stimulates renin release?

Decrease in BP
Decrease in GFR
Renal sympathetic nerve activation
Increase in Prostaglandins


How does Increase in BP stimulate renin release?

increase BP > increase afferent arteriole pressure > increase JG cell stretch (act as intrarenal baroreceptor)

> depolarize JG > Ca2+ entry LOWERS cAMP > lower renin release > less vasoconstriction and water retention


What 2 things are proportional to GFR?

Macula densa intracellular Na
(which regulates)
ATP breakdown by Na/K-ATPase


What cell in distal tubule absorb Na?

Macula densa cell


What is the effect of increased GFR on Macula densa cells?

Increase GFR > increase NaCl delivered to and absorbed by Macula Densa > Increase macula densa intracellular Na = increase Na/K-ATPase activity > more ATP converted to adenosine


What is the effect of adenosine during high GFR?

Increase adenosine > vasoconstrict AFFERENT arteriole > reduce glomerular capillary pressure > GFR lowered + renin increase


What is the effect of low GFR on Macula densa cells and renin release?

Low GFR > less NaCl delivered to and absorbed by Macula Densa > lower intracellular NaCl

> Activation of COX2 and PGE2 synthase > release of PGE2 to JG cell receptors > increase intracellular cAMP > increase renin secretion


How does Renin affect GFR and glomerular capillary pressure?

High Renin > angiotensin II > constrict renal blood vessels > efferent arteriole constrict more than afferent arteriole > Increase glomerular capillary pressure and increase GFR


Summarize the tubulo-glomerular feedback in high BP?

High BP > high GFR > low renin secretion > less angiotensin II > less constriction of renal blood vessels > lower Pgc and GFR


How does renal sympathetic nerve activation cause change in renin secretion?

Increase blood volume > Decrease renal sympathetic activity > less noradrenaline released

> less B1 receptor stimulation on JG cells > less cAMP > less renin secretion


Explain what afferent arteriole prostacyclin secretions cause change in renin release?

1) Secrete NO, PGE2, PGI2
>> stimulate renin release at JG

2) Secrete Endothelins
>>inhibit renin release at JG


4 effects of angiotensin II in body?

- Vasoconstrictor
- Increase Sodium reabsorption at kidney

-Act on brain and adrenal gland


Explain effects of angiotensin II on brain? e.g. during low BP

Increase BP by:
Increase thirst, salt appetite, ADH secretion


Explain effects of angiotensin II on adrenal gland?

Stimulate aldosterone synthesis for more Na absorption


How is BP related to angiotensin II levels?

high BP = low angiotensin II

low BP = high angiotensin II level


Explain action of angiotensin II during Hypotension?

Low BP > low GFR > high renin > high angiotensin II > renal vasoconstriction (increase BP and TPR)


How does high angiotensin II change renal blood flow, glomerular capillary pressure and GFR?

Angiotensin II > efferent arteriole constrict more than afferent > lower renal blood flow, but higher Pgc and GFR

Maintains adequate GFR despite decreased renal blood flow


Effect of angiotensin II at very low BP?

Widespread vasoconstriction throughout body


How does angiotensin II stimulate Sodium re-absorption at kidney?

 At apical membrane: stimulate:
- Na/H exchanger in PCT
- Epithelial Na channel (ENaC) in principal cells

 At basolateral membrane: stimulate:
- Na-HCO3 - cotransporter in intercalated cells
- Na/K-ATPase


Explain the effects of angiotensin II on brain? (stimulate salt appetite, ADH release, thirst)

Angiotensin II cannot cross BBB

> act on 3 circumventricular organs (Area Postrema, Subfornical Organ, Organum Vasculosum)

> stiumulate other areas of brain for effects


How does angiotensin II affect aldosterone level?

Angiotensin II stimulates synthesis + release of aldosterone


What two things increase synthesis of aldosterone?

high K+ conc in ECF

Angiotensin II


Where is aldosterone made?

Adrenal cortex


Explain action of aldosterone on Na+ levels?

Increase Aldosterone > increase activity of Na/K pump at distal tubule basolateral membrane > increase Na+ conc. gradient > more Na+ reabsorption


Explain action of aldosterone on K+ levels?

Increase Aldosterone > increase activity of Na/K pump at distal tubule basolateral membrane > increase K+ conc. gradient > more K+ excretion into filtrate


What channel does aldosterone increase in renal tubule?

aldosterone increases epithelial Na+ channel (ENaC) in collecting tubule to increase Na reabsorption


What ion is also excreted in Angiotesin II action on Na/K pump ?

increase Na reabsorption and increase K excretion > more H+ excreted into filtrate


Where are the components of intrarenal renin-angiotensin system made ?

JG = renin
PCT = angiotensinogen + ACE
AT 2 receptor made throughout kidney

AT II made within kidney


How is brain RAS kept separate from systemic RAS?

due to BBB blocking angiotensin movement


Which angiotensin receptor is found in brain? Activated by which angiotensins?

AT I receptors

activate by angiotensin II and III


What converts angiotensin I to III in brain RAS?

1 > 2 :ACE
2 > 3: Aminopeptidase


4 effects of brain RAS?

increase sympathetic NS activity in CVS

Increase ADH, thirst

Modulate baroreflex sensitivity


Summarize effect on RAS by decreased blood volume?

Low BV = increase R,A,A
Increase salt and water retention
Blood volume increase to normal


What are the differences between AT 1 and AT2 receptors

AT1: vasoconstriction, sympathetic activation, Na+ and fluid retention

AT2: Vasodilation, inhibit cell growth and apoptosis


Summarize effect on RAS by Increased blood volume?

Decrease R,A,A
Less salt and water retention
blood volume reduce to normal


How does salt retention result from heart failure ?

Heart failure > hypotention > reduce renal blood flow and GFR > increase renin > increase angiotensin II > increase vasoconstriction and salt reabsorption from kidneys > salt retention


How does high blood volume affect ANP level?

High BV > high BP > increase stretch of atrial muscle cells > release of secretory granules > more ANP released


Where does ANP act?

mainly on PCT to produce natriuresis (Na loss)


What is full name of ANP?

Atrial natriuretic peptide


4 actions of ANP in high BP?

Increase GFR

decrease Na reabsorption

Decrease renin secretion

Inhibit effects of ADH


Explain effect of ANP on GFR?

High ANP > dilate AFFERENT arteriole > increase Pgc > increase GFR


Explain effect of ANP on salt reabsorption?

high BP > high ANP > inhibit action of angiotensin II on NHE > decrease Na reabsorption at PCT

Inhibit epithelial Na channel > decrease Na reabsorption at late distal tubule and cortical collecting duct


How does ANP act on Epithelial Na Channel (ENaC)?

ANP > Natriuretic peptide receptor A > increase cGMP conc. > phosphorylate ENaC > decrease Na entry to PCT > decrease Na reabsorption


How does ANP affect ADH?

ANP reduces insertion of aquaporins into collecting ducts > decrease water reabsorption


How does ANP act on RAAS?

Act on JG to reduce renin secretion > less RAAS activation > less vasoconstriction, salt and water retention


What is BNP?

B-type natriuretic peptide


Where is BNP secreted?

Secreted by heart ventricles in response to excessive stretch


What is BNP a marker for?

marker for acute congestive heart failure,


Compare BNP and ANP action?

 Binds to same receptors as ANP (ANPR A) with 10x
lower affinity
 Similar actions to ANP but much less effective

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