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Autoregulation of 
GFR 
- Dr. Garima Aggarwal 
Resident, DM Nephrology 
Amrita Institute of Medical Sciences 
Kochi, India
Renal Blood Supply
Glomerular Filtration 
• Glomerular Filtration Rate - Volume of fluid filtered from 
glomerular capillaries into Bowman’s per unit time. 
RREENNAALL PPLLAASSMMAA FFLLOOWW 
FFIILLTTRRAATTIIOONN CCOOEEFFFFIICCIIEENNTT 
STARLING’S 
FORCES
• Glomerular Hydrostatic Pressure is determined by 3 variables, each 
of which is under physiological control 
 Arterial Pressure 
 Afferent arteriolar resistance 
 Efferent arteriolar resisitance
Changes in GFR by constriction oorr ddiillaattiioonn ooff aaffffeerreenntt 
(AAAA) oorr eeffffeerreenntt (EEAA) aarrtteerriioolleess 
5
Autoregulation of GFR 
• Feedback mechanisms which are intrinsic to the kidney 
and keep the Renal Blood flow and GFR relatively 
constant despite marked changes in arterial blood 
pressure. 
• Within a range of 70- 160 mmHg 
• Without autoregulation even a slight change in BP 
would cause a significant change in GFR 
• For eg at 100mmHg – 180l/day GFR, 1 l/day of urine 
If 25% rise in BP to 125mmHg – 225l/day of GFR 
46l/day of Urine !!!!
Other Factors involved in Autoregulation 
 Neural 
 Hormonal 
 Vasoactive Substances
Myogenic Mechanism 
• Arterial smooth muscle contracts and relaxes in response 
to increases and decreases in vascular wall tension. 
• It contributes upto 50% of total autoregulatory response 
• Occurs very rapidly, reaching a full response in 3-10 
seconds 
• It is a property of the preglomerular resistance vessels – 
arcuate, interlobular and the afferent 
• It is not seen in efferent arterioles, probably because of 
lack of voltage gated Ca channels
Mechanism of Myogenic Autoregulation 
Arterial Blood pressure 
Afferent Arteriolar Blood pressure 
Arterial wall stretch 
Sensing by myogenic stretch receptors 
Opening of voltage gated Calcium channels 
Influx of Ca from ECF to Vascular SM cells 
Contraction of Vascular Smooth Muscle cells 
Vasoconstritction 
Minimizes changes in Afferent arteriolar blood flow 
Minimizes changes in GFR
Tubuloglomerular Feedback 
Nephron is uniquely organised so that the same 
tubule that descends from the cortex 
eventually returns to the originating glomerulus
Juxtaglomerular Apparatus 
MMAACCUULLAA DDEENNSSAA CCEELLLLSS 
EXTRAGLOMERULAR MESANGIUM 
RENIN SECRETING CELLS of the afferent arteriole
Mechanism of Tubuloglomerular feedback 
• This is a feedback mechanism that links sodium and chloride 
concentration at the macula densa with control of renal arteriolar 
resistance. 
• It acts in response to acute perturbations in delivery of fluid and 
solutes to the JGA. 
• It has 2 components 
 Afferent arteriolar feedback 
 Efferent arteriolar feedback (hormonal) 
It helps in 
• Autoregulation of GFR 
• Controls distal solute delivery, hence Tubular Reabsorption
Tubuloglomerular feedback continued. 
Arterial Pressure 
Glomerular Filtration Pressure 
GFR 
Na and water retention by PCT 
Na delivery at Macula Densa 
Signal to Afferent arteriole Renin 
Adenosine/ATP Angiotensin II 
Aff A Resistance Eff A Resistance 
Vasodilation of AA Vasoconstriction of EA
Tubuloglomerular feedback cellular level 
TUBULE LUMEN 
MACULA DENSA 
INTERSTITIUM 
MESANGIAL CELLS 
GRANULAR CELLS 
AFFERENT ARTERIOLE
ARTERIAL PRESSURE 
GFR 
SOLUTE DELIVERY TO MACULA DENSA
Regulation of Tubuloglomerular 
feedback 
• Mediators 
Adenosine 
ATP 
• Modulators 
Neuronal NOS 
Angiotensin II 
Endothelin
Neural regulation of GFR 
 Sympathetic nerve fibers innervate afferent and efferent 
arteriole 
• Normally sympathetic stimulation is low nd has no effect on 
GFR 
• During excessive Sympathetic stimulation (Defense, Brain 
Ischemia, Severe Hemorrhage) lastin from few minutes to few 
hours can stimulate the Renal vessels 
• Vasoconstriction occurs as a result which conserves blood 
volume(hemorrhage)and causes a fall in GFR. 
 Parasympathetic Nervous System – Acetylcholine causes 
release of NO from the Endothelial cells, hence Vasodilation.
Hormonal regulation of GFR 
VASOCONSTRICTORS 
•Norepinephrine 
•Epinephrine 
Released in stressful situations, alongside the Sympathetic stimulation 
•Endothelin 
ARF, Toxaemia of pregnacy, Vascular Injury, Chronic uraemia 
•Angiotensin II. 
Produced by Renin, released by JGA cells 
•Leukotrienes – LTC4, LTD4 
VASODILATORS 
•NO 
•Prostaglandin E2 
•Prostaglandin I2 
•Bradykinin 
•Leukotriene LTB4
Renin-Angiotensin System: 
¯ renal blood flow &/or ¯ Na+ 
++ Juxtaglomerular apparatus of kidneys 
(considered volume receptors) 
Renin 
Angiotensin I 
Aldosterone 
Adrenal 
cortex 
Corticosterone 
Angiotensinogen 
(Lungs) 
Converting 
enzymes 
Angiotensin II 
(powerful 
vasoconstrictor) 
Angiotensin III 
(powerful 
vasoconstrictor) 
N.B. Aldosterone is the main regulator of Na+ retention.
REFERENCES 
1.Brenner and Rector’s- The Kidney, 9th Edition 
2.Guyton and Hall- Textbook of Medical Physiology, 11th Edition 
3.Uptodate.com 
4.Tubuloglomerular Feedback and the Control of Glomerular 
Filtration Rate Volker Vallon, Physiology 18:169-174, 2003 
5.Glomerulotubular Balance, Tubuloglomerular Feedback, and 
Salt Homeostasis, Journal of American society of Nephrology 19: 
2272–2275, 2008
Thank you for your 
patience
Autoregulation of Glomerular Filtration Rate

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Autoregulation of Glomerular Filtration Rate

  • 1. Autoregulation of GFR - Dr. Garima Aggarwal Resident, DM Nephrology Amrita Institute of Medical Sciences Kochi, India
  • 3. Glomerular Filtration • Glomerular Filtration Rate - Volume of fluid filtered from glomerular capillaries into Bowman’s per unit time. RREENNAALL PPLLAASSMMAA FFLLOOWW FFIILLTTRRAATTIIOONN CCOOEEFFFFIICCIIEENNTT STARLING’S FORCES
  • 4. • Glomerular Hydrostatic Pressure is determined by 3 variables, each of which is under physiological control  Arterial Pressure  Afferent arteriolar resistance  Efferent arteriolar resisitance
  • 5. Changes in GFR by constriction oorr ddiillaattiioonn ooff aaffffeerreenntt (AAAA) oorr eeffffeerreenntt (EEAA) aarrtteerriioolleess 5
  • 6. Autoregulation of GFR • Feedback mechanisms which are intrinsic to the kidney and keep the Renal Blood flow and GFR relatively constant despite marked changes in arterial blood pressure. • Within a range of 70- 160 mmHg • Without autoregulation even a slight change in BP would cause a significant change in GFR • For eg at 100mmHg – 180l/day GFR, 1 l/day of urine If 25% rise in BP to 125mmHg – 225l/day of GFR 46l/day of Urine !!!!
  • 7. Other Factors involved in Autoregulation  Neural  Hormonal  Vasoactive Substances
  • 8. Myogenic Mechanism • Arterial smooth muscle contracts and relaxes in response to increases and decreases in vascular wall tension. • It contributes upto 50% of total autoregulatory response • Occurs very rapidly, reaching a full response in 3-10 seconds • It is a property of the preglomerular resistance vessels – arcuate, interlobular and the afferent • It is not seen in efferent arterioles, probably because of lack of voltage gated Ca channels
  • 9. Mechanism of Myogenic Autoregulation Arterial Blood pressure Afferent Arteriolar Blood pressure Arterial wall stretch Sensing by myogenic stretch receptors Opening of voltage gated Calcium channels Influx of Ca from ECF to Vascular SM cells Contraction of Vascular Smooth Muscle cells Vasoconstritction Minimizes changes in Afferent arteriolar blood flow Minimizes changes in GFR
  • 10. Tubuloglomerular Feedback Nephron is uniquely organised so that the same tubule that descends from the cortex eventually returns to the originating glomerulus
  • 11. Juxtaglomerular Apparatus MMAACCUULLAA DDEENNSSAA CCEELLLLSS EXTRAGLOMERULAR MESANGIUM RENIN SECRETING CELLS of the afferent arteriole
  • 12. Mechanism of Tubuloglomerular feedback • This is a feedback mechanism that links sodium and chloride concentration at the macula densa with control of renal arteriolar resistance. • It acts in response to acute perturbations in delivery of fluid and solutes to the JGA. • It has 2 components  Afferent arteriolar feedback  Efferent arteriolar feedback (hormonal) It helps in • Autoregulation of GFR • Controls distal solute delivery, hence Tubular Reabsorption
  • 13. Tubuloglomerular feedback continued. Arterial Pressure Glomerular Filtration Pressure GFR Na and water retention by PCT Na delivery at Macula Densa Signal to Afferent arteriole Renin Adenosine/ATP Angiotensin II Aff A Resistance Eff A Resistance Vasodilation of AA Vasoconstriction of EA
  • 14. Tubuloglomerular feedback cellular level TUBULE LUMEN MACULA DENSA INTERSTITIUM MESANGIAL CELLS GRANULAR CELLS AFFERENT ARTERIOLE
  • 15. ARTERIAL PRESSURE GFR SOLUTE DELIVERY TO MACULA DENSA
  • 16. Regulation of Tubuloglomerular feedback • Mediators Adenosine ATP • Modulators Neuronal NOS Angiotensin II Endothelin
  • 17. Neural regulation of GFR  Sympathetic nerve fibers innervate afferent and efferent arteriole • Normally sympathetic stimulation is low nd has no effect on GFR • During excessive Sympathetic stimulation (Defense, Brain Ischemia, Severe Hemorrhage) lastin from few minutes to few hours can stimulate the Renal vessels • Vasoconstriction occurs as a result which conserves blood volume(hemorrhage)and causes a fall in GFR.  Parasympathetic Nervous System – Acetylcholine causes release of NO from the Endothelial cells, hence Vasodilation.
  • 18. Hormonal regulation of GFR VASOCONSTRICTORS •Norepinephrine •Epinephrine Released in stressful situations, alongside the Sympathetic stimulation •Endothelin ARF, Toxaemia of pregnacy, Vascular Injury, Chronic uraemia •Angiotensin II. Produced by Renin, released by JGA cells •Leukotrienes – LTC4, LTD4 VASODILATORS •NO •Prostaglandin E2 •Prostaglandin I2 •Bradykinin •Leukotriene LTB4
  • 19. Renin-Angiotensin System: ¯ renal blood flow &/or ¯ Na+ ++ Juxtaglomerular apparatus of kidneys (considered volume receptors) Renin Angiotensin I Aldosterone Adrenal cortex Corticosterone Angiotensinogen (Lungs) Converting enzymes Angiotensin II (powerful vasoconstrictor) Angiotensin III (powerful vasoconstrictor) N.B. Aldosterone is the main regulator of Na+ retention.
  • 20. REFERENCES 1.Brenner and Rector’s- The Kidney, 9th Edition 2.Guyton and Hall- Textbook of Medical Physiology, 11th Edition 3.Uptodate.com 4.Tubuloglomerular Feedback and the Control of Glomerular Filtration Rate Volker Vallon, Physiology 18:169-174, 2003 5.Glomerulotubular Balance, Tubuloglomerular Feedback, and Salt Homeostasis, Journal of American society of Nephrology 19: 2272–2275, 2008
  • 21. Thank you for your patience