The first step in urine formation is filtration of large
amounts of fluid through the glomerular capillaries into
Bowman’s capsule—almost 180 L/day. Most of this filtrate is reabsorbed, leaving only about 1 liter of fluid to be
excreted each day, although the renal fluid excretion rate
is highly variable, depending on fluid intake. The high rate
of glomerular filtration depends on a high rate of kidney
blood flow, as well as the special properties of the glomerular capillary membranes.
3. LEARNING OBJECTIVES
By the end of this lecture you should be
able to:
• Define GFR
• Describe the determinants of GFR
• Explain the factors affecting GFR
• Discuss the hormones and autocoids
that affect GFR
4/17/2024 3
4. GLOMERULAR MEMBRANE
• The membrane at which filtration occurs
• It is made up of 3 layers
1. capillary endothelium
2. basement membrane
3. layer of epithelial cells (podocytes)
surrounding the capillaries
4/17/2024 4
9. SELECTIVITY OF GLOMERULAR MEMBRANE
Filtration rate is inversely proportional to the
Molecular Weight. Water with highest filterability and
albumin with lowest
• The pore size is 8 nanometer
• Albumin is also not filtered because of its negative
charge repulsed by the negatively charged
glomerular capillary proteoglycans
4/17/2024 9
12. GLOMERULAR FILTRATION
RATE (GFR)
Glomerular Filtration Rate is defined
as volume of filtrate formed each
minute by both Kidneys.
Normal/ Average Adult GFR =
120 - 125 ml/ min or 180L/day
4/17/2024 12
13. GLOMERULAR FILTRATE
• The filtrate is devoid of proteins
and RBC
• The concentration of filtrate is
similar to ?????.
4/17/2024 13
14. GLOMERULAR FILTRATE
• The filtrate is devoid of proteins
and RBC
• The concentration of filtrate is
similar to plasma.
4/17/2024 14
15. RENAL BLOOD FLOW
• Renal blood Flow is 22% of the
cardiac output or 1100 ml/min
• Renal plasma flow is 55% of the
RBF approximately 600ml/min
• GFR is 20% of the renal plasma
flow
4/17/2024 15
16. FILTRATION FRACTION
• Filtration fraction is the fraction
of plasma which is filtered.
• Filtration fraction =GFR/RPF
=125/600
=0.2
4/17/2024 16
18. FILTRATION COEFFICIENT
(KF)
Kf = the product of the hydraulic
conductivity and surface area of
the glomerular capillaries.
GFR = Kf × Net filtration pressure
Kf =????
4/17/2024 18
22. NET FILTRATION PRESSURE
• sum of capillary hydrostatic pressure minus
the colloid osmotic pressure plus the
bowman's capsular pressure
• 60-(32+18)=10mmHg
• Capillary hydrostatic pressure is the outward
force (60 mmHg)
• Colloid osmotic and bowmans pressure are
inward forces (32mmHg+18mmHg)
4/17/2024 22
23. DETERMINANTS OF GFR
GFR=Kf x net filtration pressure
Net filtration pressure depends on three
forces
1. capillary hydrostatic pressure
2. capillary colloid osmotic pressure
3. bowman's capsular pressure
4/17/2024 23
24. 1)Increased Glomerular Capillary Filtration
Coefficient (Kf) Increases GFR
2) Increased Bowman’s Capsule Hydrostatic
Pressure Decreases GFR
3) Increased Glomerular Capillary Colloid
Osmotic Pressure Decreases GFR
4) Increased Glomerular Capillary Hydrostatic
Pressure Increases GFR
4/17/2024 24
25. 1)Increased Glomerular Capillary
Filtration Coefficient Increases GFR
Kf = GFR/Net filtration pressure
Total GFR = 125 ml/min
Net filtration pressure = 10 mm Hg
The normal Kf is = 12.5 ml/min/mmHg of
filtration pressure.
4/17/2024 25
26. 1)Increased Glomerular Capillary
Filtration Coefficient Increases GFR
Some diseases lower Kf by
Reducing the number of functional
glomerular capillaries(thereby reducing the
surface area for filtration)
Increasing the thickness of the glomerular
capillary membrane and (reducing its
hydraulic conductivity).
Example: chronic, uncontrolled hypertension
and diabetes mellitus
4/17/2024 26
27. 2-INCREASED BOWMANS
HYDROSTATIC PRESSURE INCREASES
GFR
Stones that lodge in the urinary tract
obstruct outflow of the urinary tract
and raise the Bowman’s capsule
pressure causing reduction of GFR.
.
4/17/2024 27
28. 3) Increased Glomerular Capillary Colloid
Osmotic Pressure Decreases GFR
Filtration fraction = GFR/Renal plasma flow
= (125ml/m)/(650ml/m)
= 0.2
Increases in the filtration fraction
increases the plasma colloid osmotic
pressure as the proteins are
concentrated in the glomerular capillary
4/17/2024 28
29. 4) Increased Glomerular Capillary
Hydrostatic Pressure Increases GFR
Glomerular hydrostatic pressure is determined
by three variables:
(1) arterial pressure,
(2) afferent arteriolar resistance, and
(3) efferent arteriolar resistance.
• Constriction of afferent arterioles reduces GFR.
• Modest efferent constriction raises GFR, but
• Severe efferent constriction tends to reduce
GFR.
4/17/2024 29
31. Others Factors Affecting the GFR
• Changes in renal blood flow
• Changes in systemic blood pressure
• Afferent or efferent arteriolar constriction
• Edema of kidney inside tight renal capsule
• Changes in concentration of plasma proteins:
dehydration, hypoproteinemia, etc (minor factors)
• Changes in glomerular capillary permeability
• Changes in effective filtration surface area.
• Contraction of mesangial cells: Decreases GFR by
reducing the Kf due to reduction in surface area for
filtration
4/17/2024 31
33. Factors which can decrease GFR
• Kf in DM, HTN, renal diseases
• PB in urinary tract obstruction
• GC oncotic pressure due to RBF or in plasma
proteins
• PG
1. ABP
2. angiotensin II
3. sympathetic stimulation leading to
vasoconstiction RBF in afferent arteriole
4/17/2024 33
34. Factors That Can Decrease the Glomerular Filtration Rate
(GFR)
4/17/2024 34
Thus slit pores are formed between the capillary fenestrations and podocytes
Extraglomerular mesangeal cells: They resemble smooth muscle cells and play a role in renal autoregulation of blood flow to the kidney and regulation of systemic blood pressure through the renin–angiotensin system.
Intraglomerular mesangeal cells:The primary function of mesangial cells is to remove trapped residues and aggregated protein from the basement membrane thus keeping the filter free of debris.