Glomerular filtration rate
[Ref: AV6:Chp2]
Normal values
- GFR
= 180L/day or
= 125mL/min
- Renal blood flow
= 24% of cardiac output
= 1200 mL/min
- Renal plasma flow
= RBF x (1-Hct)
= 1200 x 0.55
= 660 mL/min
- GFR
= 125 mL/min
- Filtration fraction
= GFR/RPF
= 20%
Filtration process
Filtrates go through
- Fenestrae in the glomerular capillary endothelial layer
- Basement membrane
- Slit diaphragms between podocyte foot processes
Properties that influence filtration
Filtration depends on
- Molecular size
- Electrical charge
Molecular size
MW < 7000d
--> Passes freely
[WG21:p710] <3.6-4nm --> Also pass freely if neutral or cation
Electric charge
Barrier is negative charged
Thus,
- Filtration is better in positively charged macromolecules
* Then neutral ones
* Then negative ones
- Electric charge matters only for larger molecules.
--> Small ions like Cl- still filter freely.
Starling forces
GFR = k x (HPc-HPb-OPc)
- k = filtration coefficient
- HPc = hydrostatic pressure in glomerular capillaries
- HPb = hydrostatic pressure in Bowman's capsule
- OPc = oncotic pressure in glomerular capillaries
- OPb = oncotic pressure in Bowman's capsule
* Insignificant
NB:
- A major cause of decreased GFR in renal disease is not due to changes in these parameters in the individual nephrons but due to decrease in the number of functioning nephrons
Filtration coefficient
Contraction of glomerular mesangial cells
--> Reduction in area available for filtration
--> Increase filtration coefficient
--> Decrease GFR
Hydrostatic pressure in glomerular capillaries
Vasoconstriction of the afferent arteriole
--> Reduction in HPc
--> Decrease GFR
Vasoconstriction of the efferent arteriole
--> Increase in HPc
--> Increase GFR
Thus,
GFR can be regulated independently of RBF.
Hydrostatic pressure in Bowman's capsule
Significant only in cases like urinary tract obstruction.
Oncotic pressure in glomerular capillaries
Oncotic pressure of plasma increases progressively as it moves from the afferent arteriole to the efferent arteriole side
- Because of protein-free fluid being filtered out of the capillary.
Autoregulation of GFR
GFR is strongly influenced by renal arterial pressure
Increase in BP
--> Increased salt and water excretion
--> i.e. Pressure natriuresis and diuresis
However
- Autoregulations blunt changes in GFR
Autoregulation of GFR
Myogenic autoregulation blunts changes in GFR due to changes in blood pressure
--> But the small changes in BP and GFR still cause large changes in urine output
Autoregulation of RBF
- Between 90mmHg and 200mmHg, small changes in RBF
- Below 90mmHg, strong sympathetic stimulation causes marked decrease in RBF
* via alpha1-receptor
--> Constriction of the arterioles
NB:
- Autoregulation of RBF is when MABP is between 75mmHg and 160mmHg
* As opposed to 90mmHg and 200mmHg
* [KB2:p74]
- Mechanisms of RBF autoregulation:
* Tubuloglomerular feedback
* Myogenic autoregulation
- Myogenic mechanism autoregulates both RBF and GFR
* Possible mediators = adenosine, NO, and H+
Regulation of RBF
[WG21:p707]
Renal sympathetic nerve activity
* Strong sympathetic stimulation causes a marked decrease in RBF (mediated by alpha1-receptors)
Angiotensin II
* Efferent more than afferent
RBF is decreased during exercise and on standing
Regulation of GFR
GFR is mostly controlled by changing the resistance of the afferent arterioles and efferent arterioles
GFR is decreased by
- Renal sympathetic nerve activity
* Via arteriolar vasoconstriction
- Angiotensin II level
* Via arteriolar vasoconstriction
* Also by causing mesangial contraction
Other factors that influence GFR
- Changes in filtration coefficient
- Changes in the Starling forces
- Changes in RBF
- Changes in BP
NB:
- In a normal resting person on American diet, contribution of sympathetic activity to renal vessel tone is small.
--> Increase ECF
--> Decreased sympathetic activity
--> Vasodilation (but very small)
- Autoregulatory intrarenal prostagladin production (PGE2) vasodilates
--> Blunts effect of increased angiotensin II and renal sympathetic nerve activity
Other notes
- Glomerular BP ~ 60mmHg
- Peritubular capillary BP ~ 20mmH
