Autoregulation of GFR

- Dr. Garima AggarwalResident, DM Nephrology

Amrita Institute of Medical SciencesKochi, India

Renal Blood Supply

Glomerular Filtration• Glomerular Filtration Rate - Volume of fluid filtered from

glomerular capillaries into Bowman’s per unit time.

RENAL PLASMA FLOWRENAL PLASMA FLOW

FILTRATION COEFFICIENTFILTRATION COEFFICIENT

STARLING’S FORCES

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

5

Changes in GFR by constriction or dilation of afferent Changes in GFR by constriction or dilation of afferent (AA) or efferent (EA) arterioles(AA) or efferent (EA) arterioles

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 AutoregulationArterial 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

Nephron is uniquely organised so that the same tubule that descends from the cortex eventually returns to the originating glomerulus

Tubuloglomerular Feedback

Juxtaglomerular Apparatus

MACULA DENSA CELLSMACULA DENSA CELLSEXTRAGLOMERULAR 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 PRESSUREGFR

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 GFRVASOCONSTRICTORS•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

Aldosterone

Adrenalcortex

Corticosterone

Angiotensinogen

(Lungs)

renal blood flow &/or Na+

++ Juxtaglomerular apparatus of kidneys

(considered volume receptors)

Angiotensin I Convertingenzymes

Angiotensin II(powerful

vasoconstrictor)

Angiotensin III(powerful

vasoconstrictor)

Renin-Angiotensin System:

N.B. Aldosterone is the main regulator of Na+ retention.

REFERENCES1.Brenner and Rector’s- The Kidney, 9th Edition2.Guyton and Hall- Textbook of Medical Physiology, 11th Edition3.Uptodate.com4.Tubuloglomerular Feedback and the Control of Glomerular Filtration Rate Volker Vallon, Physiology 18:169-174, 20035.Glomerulotubular Balance, Tubuloglomerular Feedback, and Salt Homeostasis, Journal of American society of Nephrology 19: 2272–2275, 2008

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