Renal Physiology

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Renal Hemodynamics II

Chris Baylis, PhD

Learning Objectives: To learn and understand:

That the physical factors that control GFR, are:

• Number of functional glomeruli. • The rate of filtration at each glomerulus,

determined by The Starling pressures acting across the GC

wall The filtration surface area and water

permeability (=Kf).

CONTROL OF GLOMERULAR FILTRATION RATE (GFR).

GFR is very high. ~100-300L of plasma water filtered every day. The plasma volume is ~3-4 L.

Consistent with the primary role of the kidney;

To monitor and control the volume and composition of the body fluids.

GFR is proportion to body size. Often corrected to 1.73 meters sq. body surface area (SA).

Determinants of Glomerular Filtration Rate

1). # of functioning glomeruli. In man, there is an average of ~1 million glomeruli per kidney, endowed at birth. Glomerular number varies widely (~250,000 to 2 million). Fewer glomeruli pre-dispose to cardiovascular and renal disease.

During development of renal disease, glomeruli become injured and then lost.

2). Filtration rate at each single glomerulus. Normally, all glomeruli are always functioning.

Regulation of GFR is by control of single nephron GFR (SNGFR).

Filtration: determined by the Starling pressures, the filtration area and water permeability.

Fluid flux across capillary wall is determined by net driving pressure (outward or inward) x water permeability x total area.

The driving pressure is determined by the balance between hydrostatic (fluid) pressure gradient across the capillary wall (trying to force fluid out) and the colloid osmotic pressure gradient (trying to pull fluid in).

In most capillaries, filtration occurs at the arteriolar end, absorption occurs at the venular end.

Unlike peripheral capillaries, only filtration of water occurs at the glomerulus and only reabsorption of water occurs at the peritubular capillary.

Fluid flux across the glomerular wall at single glomerulus = single nephron glomerular filtration rate (SNGFR)

PGC is ~ 55 mmHg. Bowman’s space (capsule) fluid pressure, PBS is ~ 10 mmHg. The pressure difference (P = PGC – PBS), drives filtration. GC colloid osmotic (oncotic) pressure, πGC varies, starting at ~ 25 mmHg and rising to 35-45 mmHg. This opposes filtration. Note: There is no filtered protein, πBS = 0.

SNGFR = [ (PGC -PBS) - (GC -BS)] x H2O perm x surface area SA

= (P - ) x kf

= PUF x kf

Another empiric definition of GFR is:

GFR = RPF x FF where RPF is renal plasma flow and FF is filtration fraction, i.e., that fraction of plasma filtered during flow through the glomerulus.

GFR = RPF x FF 120 ml/min = 600 ml/min x 0.2 (20%) Increase FF to 0.25, GFR = 150 ml/min. Increase RPF to 800ml/min with FF = 0.25, GFR =

200ml/min.

Overall, the following factors determine Glomerular Filtration Rate

1. Renal Plasma Flow, RPF

2. The determinants of Filtration Fraction (FF): These are:

a. Transcapillary Hydrostatic Pressure Gradient (P=PGC -PBS).

b. Glomerular Capillary Ultrafiltration Coefficient, Kf = water permeability x surface area

c. Oncotic pressure of blood arriving at Glomerulus (A) due to nonfilterable plasma proteins.

40 P a b c Pressure mm Hg  0 Beginning End Distance along the glomerulus

πA=20

Renal Plasma Flow (RPF) Most important physiologic determinant of GFR. GFR = RPF x FF How does this control GFR via Starling determinants? SNGFR = (P - ) x kf RPF is increasing from a – c. Increasing RPF reduces the rate of rise of , the pressure opposing filtration.

Hidden slide: In this example, only RPF is changing; πA, P and Kf all remain the same.

At the the beginning of the glomerulus, the pressure driving filtration is always the same, P (40mmHg) - πA (20mmHg) = 20 mmHg.

At low RPF (200ml/min) (curve a) water leaves the glomerulus by filtration and the glomerular protein concentration (πGC) rises rapidly until it equals and opposes P, when filtration stops. The FF=0.2 so GFR= 40 ml.

At intermediate RPF (400 ml/min) (curve b), the same amount of water leaves at the beginning of the glomerulus but from a larger plasma volume, so the rate of rise of πGC is attenuated. The net pressure driving filtration, averaged over the glomerulus therefore increases which increases filtration. FF still = 0.2, now GFR = 80 ml/min.

Hidden slide cont: In this example, only RPF is changing; πA, P and Kf all remain the same.

For both curves a and b, filtration stops only when πGC rises to equal and oppose P. In both cases FF = 0.2.

At high RPF (800ml/min) (curve c), the same amount of water leaves at the beginning of the glomerulus but from an even larger plasma volume, so the rate of rise of πGC is more attenuated. The net pressure driving filtration, averaged over the glomerulus increases even more which further increases filtration. In this example RPF is so high that πGC cannot increase enough to equal and oppose P before the available filtration surface is exceeded. In this situation, there is a net +ve filtration pressure at the end of the glomerulus and therefore FF falls (in this example to 0.18). So GFR = 144 ml/min.

NOTE: This is a “flow dependent” process.

The overall principle is that as RPF increases, GFR increases because the filtration pressure increases, due entirely to a reduction in πGC. In this example πA, P and Kf are all unchanged.

Transcapillary Hydrostatic Pressure Gradient (P = PGC –PBS).

An increase in P (from line a to b) increases net filtration pressure which increases GFR by increasing FF.

P

b 40 pressure mmHg a 

0

distance along glomerulus

HIDDEN SLIDE

P is controlled by glomerular capillary blood pressure (PGC ). An increase in PGC increases P which increases FF and GFR.

P can also be altered by a change in Bowman’s space fluid pressure (PBS) which opposes filtration. If PBS rises (as occurs with obstruction to outflow, Eg. Enlarged prostate), P will fall, leading to a fall in FF and GFR.

PBS is not physiologically regulated. PGC is regulated by the tone of the afferent and efferent arteriole resistances.

Glomerular Capillary Ultrafiltration Coefficient, Kf Kf = filtration surface area (SA) and water permeability.

P pressure  mmHg a b distance along glomerulus P pressure  mmHg a b distance along glomerulus

Variations in Kf can influence glomerular filtration rate, probably by control of SA.

If area (distance along glomerulus) increases from a to b during filtration pressure equilibrium there is no effect on filtration pressure or GFR but during filtration pressure disequilibrium GFR will rise.

Oncotic Pressure of the Blood Arriving at the Glomerulus (A).

Changes in oncotic pressure are inversely related to GFR, by reduction of net filtration pressure. When plasma protein concentration falls from a to b, GFR will increase. In practice systemic plasma protein concentration does not change in normal man.

P 40 a 

pressure b mmHg distance along glomerulus

Summary of key concepts. • The normal GFR is high because of the high RPF

and the high FF (because of high PGC and Kf). • As glomerular filtrate leaves the capillary, the

concentration of the trapped plasma proteins increases causing an increased πGC which opposes filtration.

• An increased RPF increases GFR because the filtration pressure rises due to reduction in rate of rise in πGC.

• An increased FF increases GFR because of increased PGC or Kf.

• A fall in plasma protein concentration will also increase FF but plasma protein concentration is ~ constant in the absence of disease.