Describe the factors that determine the filtered load of a substance at the renal glomerulus.

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College Answer

A good place to start was with the correct equation for a filtered load and a description of the
components. Better answers described the components and how they differ and change over
the glomerulus. Many candidates usefully based answers around the Starling forces.

A summary of factors including the role of plasma concentration, protein binding, molecular size
and charge was required to pass. Many answers gave examples for the effects of size and
charge and relate endocrine responses to specific alterations in arteriolar tone and how this
affected filtration. A detailed discussion of cardiovascular and endocrine responses to
hypovolaemia was not required.

Some candidates confused clearance with filtered load. Candidates are reminded to write
legibly - especially where subscripts and Greek letters are used. Directional arrows (if used)
should correlate with text.

Discussion

Glomerular ultrafiltration is described by the Starling equation:

GFR = Kf [ (Pgc - PBC) - σ(Πgc - Πi) ]

where

  • GFR is the glomerular filtration rate, 
  • K 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
  • Pgc  is the glomerular capillary hydrostatic pressure
  • PBC  is the hydrostatic pressure of fluid in Bowman's capsule
  • σ is the reflection coefficient for blood protein
  • Πgc is the oncotic pressure in the glomerular capillary blood,  
  • ΠBC 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)

References

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.