Determinants of Glomerular Filtration Rate

1. Determinants of GlomerularFiltration Rate Figure 26-12; Guyton and Hall GFR = Kf x Net Filt. Press • Kfis intrinsic permeability and surface area available of glomerulus-not really controllable, but number one reason why GFR changes • NFP is the sum of the hydrostatic and colloid osmotic forces • Note: ΠB is so low, can be considered zero • ΠGC does change through glomerulus, but not big determinant

2. Net Filtration Pressure 14 PG = 60 G = 28 PG = 60 G = 36 6 PB = 18 Other Forces that are NOT usually regulators of GFR • πG • PBC=Typically 18mmHg • If it increases, GFR decreases • Tubular Obstruction • kidney stones • tubular necrosis • Urinary tract obstruction • Prostate hypertrophy/cancer

3. Normal kidney 80 60 Glomerular Hydrostatic Pressure (mmHg) Kidney disease 40 20 0 Arterial Pressure (mmHg) 150 200 50 100 Glomerular Hydrostatic Pressure (PG)-Can be changed to alter GFR • Is the determinant of GFR most subject to physiological control • Factors that influence PG • arterial pressure (effect is buffered by autoregulation, see later slides) • afferent arteriolar resistance • efferent arteriolar resistance- High-resistance vessels. Efferent is narrower than afferent arteriole and so blood pressure is EXTREMELY high. • RBF and GFR are maintained relatively constant from 90mm- 180mmHg due to autoregulation

4. Re PG PG Ra Blood Flow Blood Flow GFR GFR Ra GFR + Renal Blood Flow Re GFR + Renal Blood Flow Effect of Afferent and Efferent Arteriolar Constriction on Glomerular Pressure R stands for “RESISTANCE”; NOT “RADIUS” Can reverse these to get opposite effects.

5. Summary of Determinants of GFR Kf GFR PB GFR G GFR PG GFR RA PG RE PG GFR GFR (as long as RE < 3-4 x normal)

6. GFR factors

7. GFR factors

8. Auto regulation of GFR

9. Autoregulation of GFR and Renal Blood Flow • Myogenic Mechanism • Macula Densa Feedback (tubuloglomerular feedback) –monitors NaCl levels • Angiotensin II (contributes to GFR but not RBF autoregulation) • Good for sudden changes in RBF to prevent big changes in GFR; e.g., exercise or sex

10. Myogenic Mechanism Arterial Pressure Stretch of Blood Vessel Cell Ca++ Permeability Vascular Resistance Intracell. Ca++ Blood Flow If MAP ↑ , then renal afferent arteriole constricts and Resistance ↑ So, RBF and GFR (flow) remain constant Flow=∆P/Res

11. Structure ofthe juxtaglomerular apparatus: macula densa JG cells of the afferent and efferent arterioles (granular cells) Macula densa cells of DCT Extraglomerular mesangial cells Figure 26-17; Guyton and Hall

12. Renal auutoregulation • Tubuloglomerular feedback – negative feedback between afferent arteriole and volume of filtrate • Increased flow of filtrate sensed by macula densa(juxtaglomerular apparatus) in thick ascending LH signals afferent arteriole to constrict

13. Macula Densa Feedback The reverse of this also applies: more NaCl leads to more adenosine GFR Why? Decreased GFR slows flow rate at LOH, causing increased NaCl reabsorption in ascending loop, leading to decreased NaCl in DCT Distal NaCl Delivery Macula Densa NaCl Reabsorption (macula densa feedback) Afferent Arteriolar Resistance (less adenosine and NO) GFR (return toward normal)

14. Adenosine/ATP is a powerful vasoconstrictor for the afferent arteriole • Pay attention! Adenosine was a vasodilator in a traditional systemic capillary bed! • Normal: binding of adenosine and ATP to receptors on plasma membrane of smooth muscle cells of afferent arteriole causes increased intracellular calcium and causes vasoconstriction.

15. Angiotensin II RE GFR + RBF (prevents a decrease in GFR) Renin-Angiotensin System • Renin is synthesized and stored in modified smooth muscle cells on afferent arterioles of the kidney. • Renin is released in response to a fall in pressure. Figure 19-9; Guyton and Hall

16. Macula densa feedback mechanism for GFR Autoregulation And angiotensin system augment each other Figure 26-18; Guyton and Hall

17. RA + RE GFR + RBF Despite autoregulation, RBF and GFR can be changed due to nervous input and hormones • Sympathetic nerves in kidney ONLY • Innervate efferent, afferent (and interlobular arterioles?) • Synapse on granular cells of afferent arteriole (mostly) and leads to changes in sodium and water reabsorption • Sympathetic tone elevates when ECFV decline due to : dehydration, severe emotional stress, hemorrhage, pain • RBF and GFR decline!

18. Hormones that can alter RBF/GFR • Angiotensin II- constrict afferent and efferent arteriole (mostly efferent) and decrease RBF and maintain GFR • Prostaglandins- help maintain RBF and therefore help maintain GFR, prevents renal ischemia (NSAIDS block this pathway and are contraindicated for use during hemorrhage! Elderly at risk too!) • NO- counter acts angiotensin II and sympathetic inputs as it acts as a vasodilator • Some Hypertensive patients and DM have excess NO release and this leads to increased GFR and glomerular damage from sheer stress. • Natriuretic peptides (ANP and BNP) lead to dilation of afferent arteriole and constriction of efferent arteriole so GFR is increased but RBF stays the same.