Blood volume regulation Flashcards
What is GFR?
Glomerular filtration rate
Rate of filtration from plasma to Bowman’s space
Difference between hydrostatic and osmotic pressure
Sensitive to changes to in mean arterial BP
What is Pgc and piGC?
P-GC: hydrostatic pressure of glomerular capillary - 50
pi-GC: osmotic pressure of the glomerular capillary
What happens to the pressure forces in glomerular filtration?
- Lower osmotic pressure than hydrostatic pressure in afferent arteriole - this drives fluid from capillary into Bowman’s space
- Osmotic pressure has increased but still lower than hydrostatic pressure in efferent arteriole - as plasma proteins are concentrated as fluid has filtered into Bowman’s space
- Hydrostatic pressure remains constant throughout
- Pressure within bowman’s space drives flow through the tubule
What force governs GFR? equation and meaning of symbols
Starling forces:
GFR = Kf [(Pgc - Pbs) - sigma( piGC - piBS)]
Kf: filtration coefficient - how permeable the vessel is
Pgc - Pbs: difference between hydrostatic pressure in capillary and bowmans space
piGC - piBS: difference in osmotic pressure between capillary and bowmans space
Sigma: reflection coefficient - reflection of membrane - should be 1, if zero - allows protein in = proteinuria
What is the effect of having high protein in capillaries?
Increased osmotic pressure, smaller difference between hydrostatic and osmotic pressure in capillaries > less fluid will diffuse into the Bowman’s space > lower volume of urine
What is Kf?
Filtration coefficient
How permeable the vessel is
What is sigma?
Reflection coefficient
reflective forces from the membrane
Should be 1 in the kidneys - so doesn’t allow any protein through
If zero - pathological - allows some protein through - e.g. in nephrotic syndrome
What are the different mechanisms that regulate renal blood flow?
Sympathetic nervous system
Angiotensin II
Atrial and brain natriuretic peptide (ANP and BNP)
Prostaglandins
Dopamine
Nitric oxide
How much of the cardiac output goes to the kidneys?
25%
Effect of isolated afferent and efferent arteriole constriction and dilation on Pgc and GFR
- Constriction of afferent: reduced volume entering, decreases hydrostatic pressure - less fluid diffusing out, low GFR
- Dilation of afferent: increased volume entering, greater hydrostatic pressure, greater drive of fluid out, high GFR
- Constriction of efferent: causes pressure to back up within capillary,, high hydrostatic pressure, increased GFR
- Dilation of efferent: allows blood to quickly flow through capillary, hydrostatic pressure reduced, low GFR
How does the sympathetic nervous system regulate renal BF?
Rapid onset
Stabilise mean arterial BP
Via renal sympathetic nerve
Both afferent and efferent arterioles innervated by sympathetic nerves that cause vasoconstriction by activating a1 receptors
More a1 receptors on afferent arterioles, so has greater effect on afferent arterioles
Afferent constriction > reduced hydrostatic pressure > reduced GFR
How does angiotensin II regulate renal BF?***
Potent vasoconstrictor of both afferent and efferent
Efferent arterioles are more sensitive to angiotensin than afferent
Low levels = increased GFR - more efferent constriction
High levels = decreased GFR - afferent and efferent constriction
How does atrial and brain natriuetic peptide (ANP & BNP) regulate renal BF?
Both cause dilation of afferent and constriction of efferent
Dilatory effect of ANP on afferent arterioles is greater than constrictor effect on efferent
Decrease in renal vascular resistance > increase in renal BF > increase GFR
How do prostaglandins regulate renal BF?
Produced locally in kidneys
Cause vasodilation in both afferent and efferent arterioles
Same stimuli that activate SNS and increase angiotensin II levels in haemorrhage also activate local renal prostaglandin production
Bring blood back to kidneys to return GFR to normal if ischaemic
Protective for renal BF
NSAIDs in haemorrhage > reduces RBF - endanger kidney
How does dopamine regulate renal BF?
Dopamine is a precursor to norepinephrine
Low levels: dilates cerebral, cardiac, splanchnic and renal arterioles BUT constricts skeletal muscle and cutaneous arterioles
Administered in haemorrhage treatment due to protective effect on BF in multiple critical organs incl kidneys
How does nitric oxide regulate renal BF?
Synthesised by renal endothelial cells from L-arginine
Causes dilation of renal arterioles
Protects against vasoconstriction effects of SNS
Summary:
What are the vasoconstrictors of renal arterioles
What are the vasodilators of renal arterioles
Vasoconstrictors:
Catecholamine (sympathetic),
Angiotensin II
Vasodilators:
ANP, BNP
PGI2, PGE2
Dopamine
NO
During haemorrhage, which is more likely to be released to maintain BP?
Acetylcholine, adrenaline, ANP, PGI2, PGE2
Adrenaline
What leads to the autoregulation of renal BF?
Myogenic response
Tubuloglomerular feedback
Relationship between Pa, renal BF and GFR
What is the myogenic response that leads to autoregulation of RBF?
- Increased arterial BP
- Stretch of vascular smooth muscle cells of afferent arterioles
- Activates stretch-sensitive Ca2+ permeable channels
- Cytosolic Ca2+ rise triggers smooth muscle constriction
- Afferent arteriole vasoconstricts
What occurs in tubuloglomerular feedback that leads to autoregulation of RBF?
- Increased RBF, increased GFR
> Increased delivery of Na+ and Cl- to juxtaglomerular apparatus - Release of vasoactive substance e.g. adenosine from macula densa
- Increased resistance of afferent arteriole
- Decreased RBF, decreased GFR
What is the relationship between the Pa, GFR and renal flow?
GFR tightly autoregulated by tubuloglomerular feedback and myogenic response
Autoregulatory range for RBF is 80-180 mmHg
If pressure falls below or rises above this range, can no longer autoregulate
What is filtered load?
Amount of a substance filtered into Bowman’s space per unit time
Filtered load = GFR x P[x]
P[x] is plasma conc of substance
How is Na+ gained?
Food
8g needed per day, avergae diet gets too much
How is Na+ lost?
Small amount in faeces
Small amount in sweat
Urinary excretion balances the amount ingested
100% filtered load can be reabsorbed if Na+ is limited
How does the kidney handle sodium?
Filtered into Bowman’s capsule by glomerular filtration
Majority reabsorbed in the PCT. Water follows > isosmotic
TAL reabsorbs 25% of Na+ filtered load. Water doesn’t follow, as impermeable
Early DCT reabsorbs 5% and is water impermeable
Late DCT and CD reabsorb 3% (fine tuning) site of aldosterone action
What is effective arterial blood volume?
Portion of the ECF volume contained within the arteries and is the volume perfusing the tissues
Changes in ECF volume lead to changes in the EBAV in the same direction
Oedema is the exception
What is the response to increased sodium intake?
- Increased Na+ intake
- Increased ECF volume, increased EABV, as water follows Na+
> Decreased sympathetic activity - vasodilation of afferent arterioles, increased GFR - decreased PT Na+ reabsorption - increased excretion
> Increased ANP - dilation of afferent arterioles and constriction of efferent arterioles, increased GFR - decreased Na+ reabsorption - increased excretion
> Decreased starling forces - decreased Na+ reabsorption - increased excretion
> Decreased RAAS - decreased PCT and CT Na+ reabsorption
What is the response to decreased sodium intake?
- Decreased Na+ intake
- Decreased ECF volume, decreased EABV, as water follows Na+
> Increased sympathetic activity - vasoconstriction of afferent arterioles, decreased GFR - increased PT Na+ reabsorption - decreased excretion
> Decreased ANP - constriction of afferent arterioles and dilation of efferent arterioles, decreased GFR - increased Na+ reabsorption - decreased excretion
> Increased starling forces - increased Na+ reabsorption - decreased excretion
> Increased RAAS - increased PCT and CT Na+ reabsorption
How does the kidneys handle phosphate?
Free phosphate 90% filtered across glomerular capillaries
70% reabsorbed in PCT
15% reabsorbed in PST
How does the kidneys handle Ca2+?
99% reabsorbed
Ca2+ reabsorption is tightly coupled with Na+ reabsorption in the PCT and the loop of Henle
In distal tubule reabsorption of the two ions are dissociated
How do the kidneys handle Mg2+?
95% reabsorbed
Major site of reabsorption is thick ascending limb
Also in the distal tubule
