Question 3

College Answer

Good answers included a description of Starling forces acting at the glomerular basement 
membrane. A description of the local and systemic factors influencing each component was 
expected.
It was expected candidates would discuss autoregulation of GFR & RBF, tubuloglomerular 
feedback, and integrated responses the body uses to keep GFR steady. 
Confusion about the nature of induced effects on afferent or efferent arteriolar dilation and 
constriction limited marks for some candidates. Many failed to mention the effects of mesangial 
surface area, Bowmans space pressure or serum protein content.
Candidates were expected to outline the methods of GFR estimation. Better responses 
described the rationale behind the use and limitations. Creatinine clearance, inulin and nuclear 
medicine techniques all scored marks. Some candidates made no attempt at this section and 
missed the opportunity to score marks. Estimates of CrCl/GFR [eGFR by formulae such as 
Cockcroft Gault, and serum Cr] are not measurement of GFR.

Discussion

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)

Regulation of glomerular ultrafiltration is achieved by controlling the vascular resistance of the afferent and efferent arterioles, via these factors:

• Myogenic autoregulation
• Tubuloglomerular feedback
• Sympathetic stimulation
• Angiotensin II
• Endothelin
• Prostaglandin (PGE₂)
• Protein ingestion and amino acid infusion
• Glucose (hyperglycemia)

As for "outline methods by which GFR can be measured", we're going to assume the examiners meant "briefly, in three minutes, list all the methods and marker substances you can think of". Thus:

• Glomerular filtration rate can be measured by:
  • Renal (urinary) clearance of a marker solute, where the rate of urinary clearance is used as the surrogate for glomerular filtration.
  • The formula used for this is CL_x  = (U_x × Q_u ) / P_x, where U is urine, Q is flow and P is plasma
    • Commonly used markers include:
      • Exogenous substances such as inulin (gold standard)
      • Endogenous substances such as creatinine
• Plasma clearance of a marker solute,  where the disappearance of a marker from the blood is used as a measure of glomerular filtration:
  • A known quantity of a marker substance is given intravenously
  • Its concentration in the blood is measured and plotted over time intervals
  • The clearance is calculated using the formula CL = dose / AUC
    where AUC is the area under the concentration/time curve
  • Marker substances include iohexol and radiolabelled markers
• Clearance of a radiolabelled marker from urine or plasma can be measured using nuclear medicine techniques. Popular markers include ¹²⁵I iothalamate, ¹⁶⁹Yb-DTPA, ⁹⁹Tc-DTPA and ⁵¹Cr-EDTA.

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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.