1. Glomerular Filtration Rate (GFR) and Renal Blood Flow (RBF) Beth Lee, PhD Physiology and Cell Biology The Ohio State University College of Medicine

2. Objectives Define filtration fraction. List the factors involved in determining whether a substance is freely filtered in the glomerulus. Describe how Starling forces differ between glomerular and non-glomerular capillaries. Describe the factors involved in physiological regulation of GFR. Define auto-regulation of renal blood flow and GFR. At the end of this module, you will:

3. Filtration Fraction Efferent arteriole Afferent arteriole To nephron tubules Bowman’s space Bowman’s capsule Glomerular capillaries podocytes GFR = 125 ml/min Plasma flow (RPF) = 605 ml/min Filtration fraction = GFR/RPF = 20%

4. Review of the Filtration Barrier of the Renal Corpuscle

5. The Plasma Filtrate  Freely filtered: molecules < 7 kDa  Partially filtered: molecules between 7 kDa and 70 kDa. The larger the molecule, the more poorly filtered.  A negative charge further inhibits filtration. Size and charge selectivity of the filtration barrier

6. Podocyte Loss (Effacement) Normal glomerular capillary Damaged glomerular capillary

7. Renal Blood Flow Q =  P/R where Q is organ blood flow,  P is the difference in hydrostatic pressure across the organ, and R is vascular resistance (true for all organ systems). Therefore, blood flow is directly proportional to differences in blood pressure but inversely proportional to vessel resistance. Resistance is inversely proportional to the 4 th power of the vessel radius.

8. Hydrostatic Pressure in the Renal Vasculature 110 mm Hg 60 mm Hg 20 mm Hg

9. Main Determinants of Renal Blood Flow Q =  P/R  RBF (Q) is determined mainly by  Mean pressure in the renal artery (P at input)  Contractile state of the smooth muscle in the afferent and efferent arterioles (R at the renal corpuscle) The afferent and efferent arterioles can constrict or dilate independently of each other. When they both change in the same direction, the effects on resistance are additive; when they change in different directions, the effects on resistance negate each other.

10. Review of Starling Forces  In 1896, the British physiologist Ernest Starling derived an equation that described how hydrostatic and oncotic pressures affect filtration across capillary membranes.  Recall that oncotic pressure is simply the osmotic pressure caused by the difference in protein levels between the plasma in capillaries and the external fluids.  In the Starling equation, hydrostatic (or hydraulic) pressures are designated “P”, while oncotic pressures are designated “  ”.

11. Starling Forces (non-glomerular capillary) Net filtration pressure (NFP) = P c +  IF – P IF -  c

12. Starling Forces (glomerular capillary) The term  BS is missing from the equation because there is no protein in Bowman’s space; thus no oncotic pressure. NFP = P GC – P BS –  GC

13. Changes in NFP across the Glomerular Capillary

14. Glomerular vs. Non-glomerular Capillaries  The glomerular system has:  higher hydrostatic pressure in capillary and little decrease in P along capillary length  lower (essentially zero) oncotic pressure in Bowman’s space (versus the interstitium)  rise in plasma oncotic pressure along capillary length  higher surface area and increased permeability

15. Starling Forces Drive the GFR GFR = capillary permeability X capillary surface area X NFP GFR = K f X NFP GFR = K f X (P GC – P BS –  GC ) K f is termed the filtration coefficient

16. Physiological Regulation of GFR by K f  Intraglomerular mesangial cells have contractile capacities, which could potentially alter K f by constricting or dilating glomerular capillaries.  However, contribution of mesangial cell contractile capacities to regulation of the GFR is probably minimal. GFR = K f X (P GC – P BS –  GC )

17. Main Determinants of GFR  Recall from an earlier slide that the major determinants of RBF are (1) the mean pressure in the renal artery; and (2) the contractile state of the smooth muscle in the afferent and efferent arterioles.  These two factors are also the major determinants of GFR, but interestingly, the kidney has the capacity to regulate RBF and GFR independently. I shall discuss this phenomenon in the next two slides.

18. Physiological Regulation of GFR by P GC  A change in renal arterial pressure will change P GC, and thus GFR, in the same direction.  Renal arteriole constriction and dilation also affect P GC, but the effects on GFR depend on where these events occur. GFR = K f X (P GC – P BS –  GC )

19. How Changes in Arteriolar Resistance Alter RBF and GFR RBF RPF RBF RPF RBF RPF RBF RPF Decreased GFR Increased GFR AB CD

20. Changes in P BS can Occur in Pathological Conditions  The hydrostatic pressure of the Bowman’s space is not subject to physiological control and plays a minor role in GFR.  However, pathological conditions that create obstructions in the tubule or urinary system will increase this pressure, thus decreasing GFR. GFR = K f X (P GC – P BS –  GC )

21. Short-term Regulation of RBF and GFR  Arterial blood pressure rises and falls routinely throughout the day, based on activity level and excitement.  As we have seen, GFR can be extremely sensitive to renal arterial pressure (increased pressure causes increased GFR).  Too many changes in GFR can be damaging to the kidney. How does the body keep GFR and RBF at constant levels to prevent damage and to keep excretion relatively constant?

22. Autoregulation 0 40 80 120 160 200 240 Blood Pressure mm Hg Flow L/min 1.5 1.0 0.5 Autoregulation RBF GFR Autoregulation refers to short-term regulation of RBF and GFR in spite of changes in blood pressure.

23. Summary  Filtration fraction refers to the portion of plasma entering the kidney that is filtered, and is equal to GFR/RPF.  The filterability of solutes is dependent on both size (molecular radius) and charge.  Glomerular capillaries are different from non-glomerular capillaries in ways that allow for enormous levels of filtration.  Net filtration pressure, capillary surface area, and capillary permeability all contribute to the GFR.  Autoregulation maintains RBF and GFR at constant levels in the face of swings in mean blood pressure.

24. References  The suggested reading for this lecture is Chapter 2 of Vander’s Renal Physiology (McGraw-Hill).

26. Thank you  Thank you for completing this module. If you have any questions, please contact me.  Beth.Lee@osumc.edu Beth.Lee@osumc.edu

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