Volume regulation L11 Flashcards
How can the body measure its effective circulating volume?
body can measure volume in different parts of circulation due to presence of pressure sensors and volume sensors that are mediated by stretch, found within the cardiovascular system
What effect does a haemorrhage have on circulating volume and total extracellular volume?
- haemorrhage decreases circulating volume
- this decreases pressure in circulation
- fluid drawn from extracellular space into circulation down a pressure gradient
- total extracellular volume falls too
What is the juxtaglomerular apparatus?
juxta- next to
glomerular - glomerulus
=structures next to the glomerulus
- consists of renal afferent arteriole (granular cells) and distal convoluted tubule (macula densa)
- regulates filtration rate and blood pressure across glomerulus
What are granular cells?
- also known as juxtaglomerular cells
- present mainly in renal afferent arteriole (although a few on efferent)
- secrete renin
- stimulated by macula densa cells (detect fall in Na+) or stretch receptors that detect drops in blood pressure
Describe the renin-angiotensin-aldosterone cycle
- low Na+ in distal tubule
- detected by macula dense cells
- stimulate juxtaglomerular cells to produce renin
- renin converts angiotensinogen (produced in liver) into angiotensin I
- angiotensin I travels in circulation to lungs
- angiontensin converting enzyme (ACE) (produced in lungs) converts angiotensin I into angiotensin II
- angiotensin II stimulates the adrenal cortex to secrete aldosterone
- aldosterone travels to the kidney where it increases Na+ reabsorption in distal tubule and collecting ducts
- angiotensin II also increases Na+ reabsorption in proximal tubule (Na+/H+ exchanger) as well as efferent arteriole vasoconstriction
- Na+ concentration increases
- GFR increases
- blood pressure increases due to H20 retention
- negative feedback on system
what are the two main physiological triggers for aldosterone release?
- stimulation through angiotensin II
- hyperkalaemia
List the four groups of drugs that can inhibit the renin angiotensin system. What is the ultimate goal of inhibiting this system?
- ACE inhibitors
- Angiotensin II receptor antagonists (same as AT1-receptor antagonists)
- aldosterone receptor antagonists
- drugs that inhibit renin
decrease blood pressure
Give examples of ACE inhibitors.
ramipril, captopril, enalopril *prils
Give examples of AT1 receptor antagonists.
candesartan, irbesartan, valsartan, losartan *sartans
Give examples of aldosterone receptor antagonists.
spironolactone *look back to previous lectures!
Give examples of renin inhibitors.
aliskiren
Describe the cellular pathway that AT1 exhibits to produce responses in circulation.
- AT1 coupled to Gq protein
- Gq stimulates Phospholipase C
- PLC ultimately forms IP3 and DAG (and PiP2)
- IP3 and DAG stimulate Ca2+ release from intracelullar stores
- increased released of Ca2+ in smooth muscle cells can stimulate vasoconstriciton
- Ca2+ release in granular can stimulate them to release more renin
- both actions increase blood pressure
What is a side effect of taking ACE inhibitors?
cough
What are the five ways angiotensin II increases circulating volume?
- vasoconstriction
- stimulates aldosterone release from adrenal cortex > increase distal Na+ absorption
- increase Na+/H+ exchange in proximal tubule, hence proximal Na+ and water absorption
- cause ADH release
- causes thirst
The sympathetic nervous system can cause renin to be released from granule cells in afferent arteriole. Describe the three mechanisms of action through which this happens.
- Direct stimulation of renin release from granule cells
- sympathetic nerves release noradrenaline > detected by alpha-1 adrenoceptors on vascular muscle cells in afferent arteriole > vasoconstriction upstream from granular cells > fall in pressure downstream > sensed by beta-1 adrenoceptors on granule cell (stretch-sensitive) > renin release
- vasoconstriction of afferent arteriole (same as above) > decrease in pressure downstream (to glomerulus) > drop in glomerular hydrostatic pressure > decrease in GFR > renin angiotensin system stimulation through Na+ concentration
What are the effects of beta-blockers in the kidney?
- block beta-1 adrenoceptors in afferent arteriole
- reduce renin production
- lower blood pressure
How can a fall in blood volume stimulate renin release from kidney?
-lower blood volume = fall in venous pressure
> decreased cardiac output
> decreased blood pressure
> fall in pressure in vasa recta
> increase in fluid uptake from interstitium
> greater loss of fluid from filtrate (gradient)
> decrease in Na+ delivery to distal tubule
> detected by macula densa
> renin release from granule cells
How can a fall in blood volume stimulate ADH release from kidney?
- decreased cardiac filling >activation of baroreceptor reflex
- angiotensin II stimulates ADH release
- ADH release > increase in water reabsorption > increase in cirulating volume (however this response does decrease osmolality as does not affect Na+ reabsorption)
What body stimuli activate ADH release?
- increased osmolaliy
- stress
- decreased volume
- nicotine
What body stimuli inhibit ADH release?
- decreased osmolality
- increased volume
- alcohol
What is ANP? What does it do?
-Atrial Natriuretic Peptide
-released due to increased atrial filling (due to increased venous return)
-travels to kidney and acts on ANPa,b recpetors
> increases cGMP activity (second messenger)
ANP has different actions that all ultimately increase renal Na+ excretion (natriuretic):
- inhibits Na+/K+ ATPase > dilates afferent arteriole > increases GFR > increase Na+ to kidney > inhibits renin release
- decreases Na/Cl cotransport activity in distal tubule
- decreases ENaC activity in collecting duct
Which prostaglandins are natriuretic?
PGE2 and PGI2
*can be inhibited by NSAIDS > Na+ retention
Where is dopamine synthesised?
epithelial cells in proximal tubule of kidney
How does dopamine increase Na+ excretion?
-acts on D1 receptors to increase cAMP
-also acts to decrease activity of Na+/H+ exchanger in proximal tubule
>increased Na+ excretion
