1. Glomerular filtration rate (GFR) is the amount of filtrate formed by the glomerular filtering membrane per unit time, normally around 125 ml/min. 2. GFR is determined by factors like hydrostatic and oncotic pressure gradients across the glomerular capillaries as well as the permeability and surface area of the capillaries. 3. GFR can be affected by changes in renal blood flow, glomerular capillary pressure, capsular pressure, oncotic pressure, capillary permeability, and surface area. Substances' molecular size, shape, and charge also impact filtration.

1. Glomerular Filtration Rate
GFR

2. SLO
• At the end of the lecture you should be able to
1. Define Ultrafiltration
2. Explain glomerular filtration determining
factors
3. Define and enumerate factors affecting GFR.

3. Processes contributing to urine
formation
1. Glomerular Filtration
2. Reabsorption from tubular
lumen to peritubular
capillaries
3. Secretion from peritubular
capillaries into the renal
tubules
urinary excretion rate = Filtration
rate – Reabsorption rate +
Secretion rate
4

5. Glomerular filtration rate (GFR)
• The amount of filtrate formed by
glomerular filtering membrane
of both the kidneys in a unit time
• 125 ml/min or 180 L /day
• Urine output is about 1- 2 L /day
• About 99% of filtrate is
reabsorbed

6. Mechanism of glomerular filtration
• Ultrafiltration: It is the process of filtration
due to pressure gradient which produces a
filtrate free from cellular and colloidal
components of blood.
• Glomerulocapsular filtration barrier:
– Fenestrated capillary endothelium
– Glomerular basement membrane
– Filtration slits formed by Podocytes

7. Composition of the Glomerular
Filtrate
Devoid of cellular elements like RBC/WBC/PLT and
– Protein-free
• The concentrations of most salts and organic molecules, are similar to
the concentrations in the plasma.
– Exceptions include
• Calcium and fatty acids
• Because of the fact that, they are partially bound to the plasma
proteins.
• Almost one half of the plasma calcium and most of the plasma
fatty acids are bound to proteins, and these bound portions
are not filtered through the glomerular capillaries.

8. Importance of High GFR
• We know that,
– Entire plasma volume is only about 3 L.
– GFR is about 180 L/day
This means : the entire plasma can be filtered and processed
about 60 times each day.
• This is necessary to be able to remove waste products
“Rapidly” & “Precisely”.

10. Determining factors
• Pressure gradients
(Starling’s forces)
• Hydrostatic pressure
gradient(PG - PB)
• Oncotic / osmotic pressure
gradient (G- B)
• Filtration coefficient (Kf )
• Size of the capillary bed
• Permeability of capillaries
Glomerular filtration Kf (PG - PB) (G- B)

12. Pressure gradients (starling’s forces)
• Hydrostatic pressure gradient (PG - PB):
– Capillary hydrostatic pressure(PG)
• Afferent arteriolar end45mmHg
• Efferent arteriolar end45mmHg
– Hydrostatic pressure in bowman’s space (PB)- 10mmHg
• PG – PB 45-10 = 35mmHg- - favors filtration
• Oncotic / osmotic pressure gradient(G- B)
– Capillary oncotic pressure
• Afferent arteriolar end20mmHg
• Efferent arteriolar end35mmHg
– Oncotic pressure in bowman’s space--Zero
–Favors reabsorption

13. • Net filtration pressure gradient: (EFP)
– The difference between hydrostatic pressure
gradient and oncotic pressure gradient across the
glomerular capillary.
EFP =(PG - PB) - G

15. Calculation of GFR

16. Filtration coefficient(Kf)
• It is the product of Glomerulocapsular
filtration barrier permeability and the
effective filtration surface area.
• Kf = GFR/net filtration pressure=125/10
• 12.5 ml/min/mmHg
• Filtration barrier behaves as if it has pores
upto 60 Å in diameter.
– Fenestrae in endothelium500-1000Å
– Filtration slits by podocytes 250 Å

17. Glomerulocapsular filtration barrier
permeability
• Molecular size:
– Substrate with molecular weight upto 5000 and diameter
<4nm are filtered
– It falls with increasing weight
• Shape:
– Elongated > globular
• Electrostatic charge:
– Cations > anions
• Applied:
– Normal urine protein-100mg/day(due to shedding of
epithelial cells.)
– Albuminuria is seen in diseases which causes loss of negative
charge of the filtration barrier.(i.e in glomerular nephritis)

18. Size of the capillary bed (mesangial cells)
• Factors producing
contraction of
mesangial cells:
– Angiotensin II
– Norepinephrine
– Endothelins
– ADH
– Thromboxane A2
• Factors producing
relaxation of mesangial
cells
– Dopamine
– ANP
– PGE2
– Nitric oxide
– Bradykinin

19. • Glomerular Filtration
 Total Filtration 180l/day
 Kf 100 times higher
 Capillary hydrostatic pressure
twice high
 Total surface area is more
 Oncotic pressure varies over
the length of capillary
• Systemic Filtration
• 20l/day
• Low
• Less
• Lesser
• Does not vary.

20. Factors affecting GFR
1. Changes in renal blood flow
2. Glomerular capillary
hydrostatic pressure
3. Changes in the capsular
hydrostatic pressure
4. Oncotic pressure
5. Glomerular capillary
permeability
6. Effective filtration surface
area
7. Size, shape and electrical
charge of the
macromolecules-
<10000mol.wt

21. PGS, Kinins,
Dopamine (low
dose), ANP, NO
Angiotensin II
(low dose)
Ang II (high
dose), NE,
Endothelin,
ADH,
Angiotensin II
blockade

22. Glomerular capillary hydrostatic
pressure

23. Filtered load
• Amount of substance filtered per unit of time
is called filtered load.
• It is measured by multiplying GFR with the
plasma concentration (Px ) of the substance
Filtered load = Px . GFR . Fx
•Fx fraction of substance in the plasma that is free

24. Filtration fraction (FF)
• Fraction of plasma passing
through kidneys which is
filtered at the glomerulus.
• GFR/RPF
• 0.16-0.20
• Significance:
– Index of glomerular activity
– In hypotension decrease in
GFR less than that of RPF due
to increase in FF

25. Measurement of GFR
• Renal clearance (Cx):
– It is the volume of plasma from which the
substance (x) is completely cleared (removed) per
unit of time.
• Can be assessed by determining the
concentration of the substance in plasma (Px)
and urine (Ux) and by estimating the urine flow
rate (V)
UxV
Cx PX

26. • No single milliliter of plasma has all of its X
removed by the kidney; instead, a certain
fraction of the X in each milliliter of plasma is
removed.
• As per conservation of mass rate of removal from
plasma must equal rate of excretion
• Px Cx = UxV
• Significance:
– Virtually non invasive
– Only method available for study of renal physiology in
humans
– Evaluating the overall elimination of a substance by the
kidney
UxV
Cx PX

27. Criteria of the substance to be used
for GFR measurement
 It should be freely filtered by glomeruli
 It should neither be reabsorbed nor secreted
in renal tubule
 Should not be synthesized or stored or altered
in kidney
 It should not be metabolized in the body
 It should be nontoxic to the body
 Its concentration in plasma and urine should
be easily measured
 Inulin and Creatinine
[filtrate] / [plasma] = 1

28. Measurement of GFR by inulin
clearance
• Fructose polymer with a molecular weight
≈5000 Daltons
• It is freely filtered neither reabsorbed nor
secreted
• Mass of inulin excreted per unit of time is
equal to mass of inulin filtered per unit of
time
 UinV = PinGFR
 GFR= Cin =UinV /Pin
UinV
Cin Pin

29. Calculate GFR from given data
• Urine concentration of inulin 40 mg/ml
• Plasma concentration of inulin 0.25 mg/ml
• Rate of urine flow 0.8ml/min

30. Calculate the GFR with the given values
• Concentration of Inulin in urine =35mg/ml
• Concentration of Inulin in plasma =0.25mg/ml
• Rate of urine flow =0.9ml/min

31. Creatinine clearance(Ccr )
• Mannitol and Iothalamate can be used instead
of inulin
• Clinically creatinine clearance is used
– It is produced endogenously as end product of
creatine phosphate in muscle
– It has a stable concentration in plasma and urine.
– Does not required continuous infusion
UinV
Cin Pin

32. Regulation of GFR
• Neural regulation
• Hormonal regulation
• Autoregulation

33. Neural regulation
• Increased sympathetic
activity afferent
arteriolar constriction-
decreases GFR.
– Hypovolumia
– Exercise
– Emotions
– Fear
– Pain etc

34. Hormonal regulation
• Angiotensin
• Histamine
• Endothelin
• Adenosine
• Dopamine
• ANP
• Nitric oxide
• Bradykinin
• Prostaglandins
• Constriction of afferent A > efferent A
• Contraction of mesangial cells
• Vasoconstriction of both afferent and
efferent arterioles
• Constriction of afferent arteriole
• Renal vasodilatation & inhibits renin
secretion
• Dilatation of afferent A and constriction of
efferent A
• Vasodilatation of both afferent and efferent
arterioles
• Vasodilator
• PGE2 modulate the effects of sympathetic
stimulation and angiotensin II
(vasodilatation)

35. Autoregulation

36. Why polyuria in Diabetes?
• Large increases in blood glucose levels in
uncontrolled diabetes mellitus.
• Because glucose is also reabsorbed along with
sodium in PCT, increased glucose delivery to the
tubules causes them to reabsorb excess sodium
along with glucose.
• This, in turn, decreases delivery of sodium chloride
to the macula densa, activating a tubuloglomerular
feedback.

37. Applied aspect
• Proteinuria:
– Excess loss of proteins
in urine
• Loop diuretics
– Furosemide
– Inhibits Na+-K+-2Cl-
– Decreases blood
volume by increased
sodium and water loss
through urine
• Minimal change
disease(lipoid nephrosis)
• Membranous nephropathy
• Blunts Tubuloglomerular
feedback mechanism