Blood volume regulation Flashcards
What is GFR?
- The rate of fluid filtration from the renal capillaries into the Bowman’s space
Kf= Filtration coefficient > permeability of the capillary to water
Reflection coefficient > impermeable the capillary is to proteins
What affects the ability of the kidney to the blood?
MAP > too high = greater driving force of blood into the glomerulus capillaries, increasing the hydrostatic pressure gradient between glomerulus capillaries and bowman’s space and thus increases the glomerular filtration rate.
= Greater fluid flowing through the nephron = increases the likelihood of greater water and solute loss in our urine - making us feel dehydrated
What is the consequence of the mean arterial pressure being too low?
- There will be a reduced flow rate into the glomerulus capillaries, decreasing the pressure = too little filtration of blood into the Bowman’s space = harder to get rid of toxic waste products = these build up in bloodstream = cause unwanted symptoms
Blood entering glomerular capillaries stays constant even during changes in MAP. How does this happen?
- Changing the resistance of afferent arteriole
> MAP increases > Afferent arteriolar resistance increases = GFR remains constant
How do we change afferent arteriolar resistance when there are changes in MAP?
-> Myogenic response of the afferent arteriole (intrinsic)
>
1. Increased mean arterial pressure = pushes out harder on walls of afferent arterioles = greater outward force
2. Walls of vascular smooth muscle cells of these arterioles are stretched
3. Stretch sensitive calcium permeable ion channels within these muscle cells are activated = opening the channels
4. Causes a rise in calcium influx into the cytosolic region of smooth muscle = triggering myosin light chain kinase dependent response = triggers contraction of smooth muscle cells
5. Causing vasoconstriction of afferent arteriole = increasing its resistance
* Also reduces Renin secretion
-> Tubuloglomerular feedback
1. Increase in arterial blood pressure increases GFR
2. More fluid enters nephron = increased fluid flow to the distal convoluted tubules (DCT)
3. Macula Densa cells in the DCT sense the change in GFR and send a paracrine signal to the afferent arterioles
How do Macula Densa cells sense the change in GFR and trigger afferent arteriole constriction?
(Increased GFR as example)
- Increased GFR - increased fluid flowing to DCT + supply of ions
- Transporters in luminal membrane of Macula Densa to translocate ions at a faster rate
- Increased sodium uptake by NKCC cotransporter into Macula Densa cells
- This stimulates adenosine release from Macula Densa across the basolateral membrane into the interstitum
- Adenosine acts as a paracrine signal - binds to adenosine receptors on vascular smooth muscle cells of afferent arteriole
- Adenosine receptors trigger an increase of cytosolic calcium inside - causing **vasoconstriction of afferent arteriole **
- Thus increased resistance of afferent arteriole and GFR is back within its set limits
- Adenosine also inhibits renin secretion from granular cells in afferent arteriolar (Ca2+ rise)
How is long term mean arterial pressure controlled by changes in blood volume?
- Expand the blood volume in our systemic circulation = increases the amount of blood stored within the venous circulation (reservoir) = increased venous pressure this increases the arterial pressure.
> Detected by cardio pulmonary baroreceptors sense the pressure within great veins/right atria
lie in walls of veins/atria and respond to changes in stretch by decreasing/increasing their firing rate
Why does blood volume play a key role in determining mean arterial pressure?
- Because blood volume plays a key role in regulating venous pressure, so also the venous return to the heart = this will affect cardiac output and thus change arterial pressure
Describe what happens to MAP when blood volume decreases and increases.
Frank starling :
- Reduce SV when decreased venous pressure Increase SV when increased venous pressure.
Why can blood volume not be increased by simply drinking more fluids?
- If more water’s drunk, but urine output remains the same = blood volume will increase (only short term)
- Osmoregularity system matches the increased water uptake by matching the water output in the urine by creating a diuretic effect
- No other solutes are being taken in = so osmolarity decreases = osmoreceptors detect this change and trigger a decrease in ADH output from posterior pituitary = reduced water permeability of the collecting duct = so greater urinary output occurs
If we can’t increased blood volume by drinking more fluids how do we do it?
-
Increasing the plasma sodium content
> Increased sodium chloride intake whilst water intake remains the same = causes osmolarity of extracellular fluid to increase
> Osmoreceptors are then triggered in response to causing:
1- Thirst: As plasma osmolarity increases = feel more thirsty = so water intake increases
2- ADH output: Too much solute and not enough water = ADH output is increased = kidney will reabsorb more water = so lose less water in urine
Creates an imbalance in water intake and output = increasing the blood volume
What are the 2 different mechanisms by which the kidney responds to mean arterial pressure changes brought about reduced blood volume?
- Intrinsic: Kidney responds directly to drop in MAP caused by loss of blood volume
Explain the 3 main intrinsic responses that happen when we have reduced blood volume.
- Stabilise GFR and start to reduce urine output
Explain what pressure Diuresis and Natriuresis is?
- Increases in ABP reduces the sodium chloride and water reabsorption by the proximal tubule = increasing urine output
- Increased water excretion (diuresis) = restores blood volume to normal values
- Increased sodium excretion (natriuresis) = restores blood volume to normal values
How do extrinsic mechanisms (Neural) regulate blood volume if we loose blood volume via haemorrhage?
> Reduction in rate of firing of baroreceptors
1- Stabilise the MAP by increasing water reabsorption in the kidney and maintaining arteriolar vasoconstriction
2- Restore blood volume by increasing firing of the sympathetic nerve to the kidney, which will increase sodium reabsorption + Increase thirst/ Na+
What does an increase in Sympathetic firing frequency cause as a response to decrease in blood volume (3)?
(Neural extrinsic response)
- Increase Na+ absorption via….= increased plasma Na+ > through osmoregulatory system restores blood volume
Increased sympathetic firing as a result of decreased blood volume causes Increase Proximal tubule Na+/H+ exchange. How?
Noradrenaline increase Na+ reabsorption from the proximal tubule
1- Noradrenaline upregulates Na+/H+ exchange activity in the proximal tubule
2- Increases the sodium uptake across the luminal membrane
3- Then pumped out using the Na+/K+-ATPase into the institutional fluids across the basolateral membrane
- Can be reuptaken into the blood
Increased sympathetic firing as a result of decreased blood volume causes Vasoconstriction of both arterioles (Efferent > Afferent)
- What does vasoconstriction of the efferent and afferent arterioles maintain?
- How does vasoconstriction of both arterioles increase Na+ reabsorption?
a- GFR
b-
- Increases colloid osmotic pressure in peritubular capillaries
- Efferent and afferent contraction reduces peritubular capillary pressure
How can the isosmotic fluid reabsoption in the proximal tubule be modulated?
- altering Starling’s Forces across the peritubular capillaries (mentioned previously)
Describe the flow of the Renin Angiotensin Aldosterone system due to reduced blood flow from haemorrhage.
- Renin cleave angiotensinogen into > Angiotensin l
- ACE enzyme converts angiotensin l to angiotensin ll
- Angiotensin ll trigger Na+ reabsorption in the nephron
- Triggers the secretion of aldosterone from the zona glomerulosa cells in the adrenal gland
> aldosterone supports angiotensin II increase Na+ reabsoption in areas it does not work at (In the distal convoluted tubule and collecting ducts )
What does Angiotensin II do?
- Maintains the effects of the sympathetic nervous system on the kidneys
Works only on proximal tubles like sympathetic NS
How does aldosterone increase Na+ reabsorption in DCT and collecting ducts?
- Transcriptional/ Translational mechanism
- Steroid (hydrophobic) diffuses in and binds to aldosterone receptor which is a TF > increase transcription of certain genes and these include both epithelial Na+ channel which goes into luminal membrane of Cells in distal nephron to increase rate of Na+ reabsorption from internal lumen of nephron into cell
- Also supports transcription of Na+/K+ATPase helps pump Na+ into cell across basolateral membrane back to blood
- Also increases permeability of luminal membrane to K+ helps to secrete excess K+ into lumen
What is the timeline of response to haemorrhage?
What is secreted in response to increased blood volume?
- Atrial Natriuretic Peptide is secreted from Atrial myocytes in response to increased blood volume
