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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
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- 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 HydrostaticPressure is determined by 3 variables, each of which is under physiological control Arterial Pressure Afferent arteriolar resistance Efferent arteriolar resisitance
- 5. Changes in GFRby 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 involvedin 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 MyogenicAutoregulation 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 Nephronis uniquely organised so that the same tubule that descends from the cortex eventually returns to the originating glomerulus
- 11. Juxtaglomerular Apparatus MMAACCUULLAADDEENNSSAA CCEELLLLSS EXTRAGLOMERULAR MESANGIUM RENIN SECRETING CELLS of the afferent arteriole
- 12. Mechanism of Tubuloglomerularfeedback • 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 cellularlevel 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 ofGFR 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 ofGFR 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 andRector’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
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