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
BP = CO x TPR
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
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?
- 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
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
Where is aldosterone made?
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?
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?
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,