The basics of autoregulation of Gloemrular filtration rate. This ppt deals with basic renal physiology, tubuloglomerular feedback, myogenic reflex, juxtaglomerular apparatus and renin angiotensin aldosterone system in brief. P.S.- The ppt has animations so kindly view in slide/presentation mode

1. Autoregulation of
GFR
- Dr. Garima Aggarwal
Resident, DM Nephrology
Amrita Institute of Medical Sciences
Kochi, India

2. Renal Blood Supply

3. Glomerular Filtration
• Glomerular Filtration Rate - Volume of fluid filtered from
glomerular capillaries into Bowman’s per unit time.
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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
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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
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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