GFR

Dr D.V.Deshpande
Prof &Head
Dept of Physiology
Zydus Medical College
Dahod
 Formation of urine
Glomerular Stage-Filtrate-primitive urine

Tubular stage→Modification of filtrate

(Reabsorption,Secretion)
Glomerular Stage
Gl filtration occurs across Glomerular
membrane which is Barrier between
plasma in glomerular Capillaries & fluid in
Bowman’s capsule
1 2
 Filtration

Reabsorption

Secretion

Excretion 2
3
1 Filtration
2Reabsorption
3 Secretion
4 Excretion

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Glomerular membrane

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Fenestra 70-90
nm

Meshwork –
proteogylcan-
pores-10nm
BM
Slit pores 25nm

Glomerular
membrane
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 Glomerular membrane
1) Endothelium
2) Basement membrane of capillary
&Bowman’s capsule fused.
3) Epithelium of Bowman’s capsule

Thickness 0.3μ
SA 0.8 mt2
Filtration initial step in urine formation6
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Plasma from Glomerular capillaries filtered
via Highly permeable ( 100 times more
than capillaries elsewhere) glomerular
Membrane

Filtrate ( protein free ,cell free) enters

Bowman’s capsule
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 Filtrate identical with plasma
1. Osmolality 300 m osmol / kg water
2. PH 7.4
3. Electrolyte & non electrolyte
concentration same → Ultrafiltrate

 Energy for filtration by capillary

Hydrostatic pressure in glomerular
capillary = 60 mm Hg
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 Glomerular Filtration Rate
Definition---Quantity of filtrate from all
nephrons of both kidneys in 1 minute
125ml / min = 180 L/day
 10% less in females.

 180 L/ day = 4.5times TBW ( 40 L )

=12times ECF volume (15L)
=60 times Plasma volume (3L)
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 Starlings Forces controlling GFR.
1) Capillary Hydrostatic Pressu→60mm Hg
2) Colloid Osmotic Pressure→32 mm Hg
(plasma filtered↑conc of plasma
proteins).
3) Capsular Hydrostatic Pressure
→18mmHg.
4) COP (Bowman ’Capsule) =zero (because
no proteins).
NFP = 60 – (32+18)=10mmHg 10
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Hydrostatic Pressure > ColloidOsmotic
Pressure + Capsular Hydrostatic
Pressure→filtration
 & If equal→Filtration Equilibrium ( no
filtration)
Filtration fraction
Fraction of renal plasma that becomes
glomerular Filtrate
 125 / 650 x 100
= 18 to 20%
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 Filtartion coefficient Kf = GFR/ NFP
=125/10=12.5 ml /mm Hg/min
Kf depends on
1) Kf=Capillary Permeability x surface area
2) ↓Functioning capillaries →↓SA
3) Contraction of Mesangial cells-↓SA.
4)↑Thickness→↓Kf
5) ↑permeability( disease).

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6) Molecular size--<4nm filtered,
>8nm not filtered
7) Electrostatic charge—Glomerular
capillaries negatively charged due to sialo
proteins
Permeability of cations more than
anions&neutral molecules
Albumin diameter <8nm but is anion.
Normally albumin not filtered.
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 Normally 100mg albumin lost in urine
Not due to filtration but shedding of
tubular epithelial cells.

Albuminuria seen in glomerulo nephritis

when a)↑in pore size of glomerular
membrane b) Disruption of negative charge
of glomerular membrane.
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 Factors affecting GFR
1.Renal blood flow ↑RBF→↑GFR,
↓RBF→↓GFR.
2)Glomerular cap HP-Afferent arteriolar
constriction→↑resistance→↓HP→↓NFP→
↓GFR &vice versa
3 Capsular fluid pressure—HP in Bowman’s
capsule &tubule opposes filtration
 Ureteric obstruction→↑HP
pressure→↓ NFP →↓GFR
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4 Colloid osmotic pressure-COP ↓s filtration.:

 Hypo proteinemia→↓COP→ ↑GFR

 Dehydation→↑ COP →↓GFR.
6.BP: AR 80 to180 mm of Hg
BP <80 –GFR ↓ & > 180→↑GFR
7.Glomerular membrane diseases, thickening
& destruction→↓GFR
 Gl nephritis→↑cap permeability →↑GFR
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8.Sympathetic stimulation
Mild & moderate
Constriction of afferent arterioles
(↑reistance) =↑BP
 GFR same
 Severe ↓↓ RBF &↓GFR

9 Contraction of mesangial cells

 Distortion & encroachment of capillary
lumen→↓area for filtration→↓GFR
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Eg—ATII,ADH,NE,Endothelins
Relaxation of mesangial cells-
↑filtration Eg—ANP,NO,bradykinin

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 Physiological variations in GFR
1. Age:↑ ing age, GFR ↓s because,↓RPF &
↓renal tissue mass(Loss of nephrons)
2. Sex: Females<males
3. Posture
 Upright posture for long duration
sympathetic stimulation & ↓effective BV
( pooling) →↓GFR
supine position--↑GFR.
4. Sleep--↓Cardiac output→↓GFR
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 5.Pregnancy
 ↑BV→ , ↑CO→↑RBF & ↓vascular
resistance in renal vessels→↑GFR
Hormonal changes also responsible.
40 to 50 %↑in GFR in 2nd &3rd trimester.
6. Exercise Sympathetic Stimulation→
afferent arteriolar constriction→↓GFR
7. Weather winter & rainy season↑es
(Less loss of water) summer ↓es(↑Loss of
water-Less ECF volume) 21
 Renal clearance
Volume of plasma cleared off a substance
in 1’ by excretion in urine .
Vol of plasma contains same amount of
substance excreted in urine in 1’.
 Virtual volume
Ability of kidney to clear blood of a
particular substance
Mathematical way of expressing excretory
power of kidney
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 C = UV/ P
C: Renal clearance ml/minute
U : Urine conc of substance mg/ml
V: Rate of flow of urine ml/min
P: Plasma conc of substance in mg/ml
Principles governing renal clearance
A. Substances freely filtered , neither
reabsorbed nor secreted (inulin – GFR)
B. Filtered, Secreted & completely excreted-
RBF
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 Measurement of GFR by Clearance
Exogenous
Inulin (fructose polymer )
Endogenous
 Creatinine &urea
Criteria of Inulin Clearance
No combination with Pl Proteins-filtered
No metabolism, not produced , does not
alter GFR
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 Not toxic
Easy estimation
No reabsorption & secretion
 Filtration = excretion
 GFR X Px /ml = U x X V
 GFR= Ux X V
Px /ml

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 Creatinine Clearance
 Endogenous, Estimation simple
 Blood level constant for 24 hrs
 Collect 1 days urine sample.
 Find Urine creatinine→Ucr mg/ml
 Volume in ml /min
 plasma creatinine (Pcr mg/ml)
Creatinine Clearance
 Ccr= U cr X V/Pcr mg/ml
 P cr Inversly related to GFR 26
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 Regulation of GFR
I)Neural mechanism II)Hormonal mechanism
III)Autoregulatory mechanism---1) Myogenic
mechanism 2) Tubulo glomerular feedback
I)Neural mechanism
↓BV→↓BP→↑Symp activity→ ↑E,NE
→constriction of afferent arteriole→↓BF to
glomerulus→↓GFR
↑Symp activity in fear,anger etc.

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 II) Hormonal mechanism
1) ATII----Aff arteriolar constriction → ↓GFR
2) Histamine—arterial dilatation→↑RBF,but
contraction of mesangial cell→↓GFR
3) Dopamine a) Vasodilatation→↑RBF→
↑GFR b)Relaxes mesangial cells→↑GFR
4) Atrial natriuretic peptide---
↑BV→↑ANP→Dilatation of aff
arteriole→↑GFR→↑Urine→↓BV.

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 5)Endothelin---Secreted by endothelial cells
of renal vessels,mesangial cells,causes
vasoconstriction of aff &eff arteriole→↓GFR.
6) Nitric oxide—Vasodilatation of aff&eff
arterioles→↑GFR.
7) Adenosine-i)produced by renal tissue
ii)vasoconstriction of aff arteriole→↓GFR
iii)Role in TG feedback.
8) Gluco corticoids--↑RBF&GFR,how not
known.
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9) Prostaglandins---i) Vasodilatation
→↑RBF→↑GFR ii) Relaxation of mesangial
cells→↑GFR.
III)Autoregulatory mechanism---1) Myogenic
mechanism 2) Tubulo glomerular feedback

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Thank you

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