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

1. Fenestrae in the glomerular capillary endothelial layer
2. Basement membrane
3. 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