Question 23

College Answer

Generally this question was well answered. Almost all answers gave the correct value for GFR 
and the correct formula for Starling’s forces across the glomerular membrane.
Better answers discussed the physiological factors affecting each force (hydrostatic and 
osmotic) across the membrane in a stepwise logical manner.
Some answers discussed the control of renal blood flow; this was not expected and therefore 
was not rewarded.

Discussion

If this question was well answered, how come 60% of the candidates fail it?

Anyway:

Glomerular filtration rate (GFR) is the sum of the ultrafiltrate produced by all nephrons

• This is about 20% of renal blood flow, which itself is 20% of cardiac output
• Therefore normal GFR = about 200ml/min, or 90-120 ml/min/1.73m²

Glomerular ultrafiltration is described by the Starling equation:

GFR = K_f [ (P_gc - P_BC) - σ(Π_gc - Π_i) ]

where

• GFR is the glomerular filtration rate, 
• K_f  is the filtration coefficient of the glomerular filtration surface,
  which is itself a product of:
  • k, the hydrostatic permeability constant of the membrane, and
  • S, the surface area of the glomerular filtration surface, which can be affected by the contraction of glomerular mesangial cells
• P_gc  is the glomerular capillary hydrostatic pressure
• P_BC  is the hydrostatic pressure of fluid in Bowman's capsule
• σ is the reflection coefficient for blood protein
• Π_gc is the oncotic pressure in the glomerular capillary blood,  
• Π_BC is the oncotic pressure of the fluid in Bowman's capsule (usually zero)

Glomerular filtration of solutes is affected by:

• Molecule size: glomerular size barrier resists the passage of large molecules (>7000 Da)
  • This size barrier consists of:
    • Endothelial glycocalyx (mainly filters proteins)
    • Endothelial fenestration (60-80 nm, mainly filter cells)
    • Glomerular basement membrane (gel diffusion barrier, filters molecules by size, variable)
    • Podocyte filtration slits (3-4 nm, mainly filters proteins)
• Molecule charge:​ anionic charge of the glomerular filtration surface may resist the passage of anionic molecules​​​​​​
  • This consist of probably only the endothelial glycocalyx and the glomerular basement membrane, both of which contain a large amount of heparan sulfate proteoglycans)

Renkin, Eugene M., and Roscoe R. Robinson. "Glomerular filtration." New England Journal of Medicine 290.14 (1974): 785-792.

Pollak, Martin R., et al. "The glomerulus: the sphere of influence." Clinical journal of the American Society of Nephrology 9.8 (2014): 1461-1469.

Horster, M., and K. Thurau. "Micropuncture studies on the filtration rate of single superficial and juxtamedullary glomeruli in the rat kidney." Pflüger's Archiv für die gesamte Physiologie des Menschen und der Tiere 301.2 (1968): 162-181.

Deen, William M., et al. "Dynamics of glomerular ultrafiltration in the rat. IV. Determination of the ultrafiltration coefficient." The Journal of clinical investigation 52.6 (1973): 1500-1508.

Hoang, Khoi, et al. "Determinants of glomerular hypofiltration in aging humans." Kidney international 64.4 (2003): 1417-1424.

Deen, William M., Matthew J. Lazzara, and Bryan D. Myers. "Structural determinants of glomerular permeability." American Journal of Physiology-Renal Physiology 281.4 (2001): F579-F596.