Lecture – 2
Dr. Zahoor
1
Basic Renal Processes
 Glomerular filtration
 Tubular reabsorption
 Tubular secretion
Urine results from these
three processes.
2
Glomerular filtration
 Is the first step in urine
formation.
 Definition:
Glomerular
filtration is the transfer of
fluid and solutes from the
glomerular capillaries into
Bowman's capsule due to
pressure gradient.
3
GLOMERULAR FILTRATION
 Glomerular Filtration occurs through glomerular
membrane.
 Glomerular membrane has 3 layers:
1. Glomerular capillary endothelial cells
2. Basement membrane
3. Inner layer of Bowman’s capsule –
epithelial cells
 Important – When blood passes through glomeruli,
blood cells (RBC, WBC, Platelet) and plasma protein
are not filtered.
4
Filtration silt
Layers of Glomerular Membrane
5
6
GLOMERULAR FILTRATION
Glomerular membrane is more permeable than
capillaries elsewhere.
 WHY ? Because
i). Glomerular capillary wall has single layer of
endothelial cells. It is perforated by many large pores
called Fenestrations, that makes it 100 time more
permeable to water and solutes than other capillaries
in the body.
7
GLOMERULAR FILTRATION (cont)
ii). Basement membrane – it does not have cells, but is
composed of collagen and glycoprotein. Glycoprotein
are negatively charged.
iii). Inner layer of Bowman’s capsule – epithelial cells.
Epithelial cells are called Podocytes. Each podocyte
has foot processes.
Narrow silts between adjacent foot processes are
known as Filtration silts, they allow the fluid to enter
the lumen of Bowman’s capsule.
8
GLOMERULAR FILTRATION (cont)
 Three Forces are involved in glomerular filtration;
1. Glomerular capillary blood pressure - 55mmHg (Favors filtration)
(PGC)
2. Plasma Colloid Osmotic Pressure – 30mmHg (Opposes filtration)
(πGC)
3. Bowman’s Capsule Hydrostatic – 15mmHg (Opposes filtration)
Pressure (PBS)
Net filtration pressure = PGC - (πGC + PBS)
Net filtration pressure = 55 – (30+15) = 10 mmHg
9
10
Forces involved In Glomerular Filtration
11
FILTRATION
IMPORTANT
 Filtration through glomerular membrane also depends
on size, molecular weight and electrical charge.
E.g. Albumin – 6 nanometer
 Pores in capillary – 8 nanometer
 But Albumin is not filtered due to its negative charge,
it is repulsed by basement membrane negative
charges.
12
FILTRATION - APPLIED
 In kidney disease, we get proteinuria (protein inurine).
WHY?
 Because negative charge on basement membrane are
lost, therefore, albumin is filtered and lost in urine.
13
14
GLOMERULAR FILTRATION RATE
What is GLOMERULAR FILTRATION RATE [GFR]?
It is filtrate produced by all the nephrons of both
kidneys per minute.
 Normal GFR = 125ml/min
OR 180 liters/day
 In female, GFR = 115ml/min
OR 160 liters/day
15
GLOMERULAR FILTRATION RATE
 GFR depends on
1. Filtration Pressure
2. Glomerular Surface Area
3. Permeability of Glomerular Membrane
 These properties of Glomerular membrane (surface
area and permeability) are referred as filtration
coefficient (Kf).
 GFR = Kf × net filtration pressure
16
GLOMERULAR FILTRATION RATE
 Factors affecting GFR
1-Increased Glomerular Capillary Hydrostatic Pressure
(PGC) -> increase GFR
2-Increase colloid osmotic Pressure (πGC)-> decrease GFR e.g.
Dehydration, Diarrhea
3-Increase Bowman’s capsule Pressure (PBS)->decrease GFR e.g.
urinary tract obstruction, enlarged prostrate
17
GLOMERULAR FILTRATION RATE
 Other factors
1. If afferent arteriole is constricted by epinephrine,
norepinephrine, Endothelin (increased resistance), blood
flow will decrease, therefore, GFR will decrease
2. If afferent arteriole dilate by Nitric oxide,
Prostaglandin(decreased resistance), blood flow will
increase, therefore, increase GFR
3. If efferent arteriole constrict by Angiotensin- II, pressure
in glomeruli will increase, therefore, increase GFR
18
Adjustments of Afferent
Arteriole Caliber to Alter
The GFR
19
20
GFR IS AFFECTED BY CHANGES IN
FILTRATION COEFFICIENT
 Filtration coefficient (Kf) depends on glomerulus
surface area and permeability of glomerular
membrane.
 Kf can be modified by contractile activity in the
glomerular membrane by mesangial cells and
Podocytes, foot processes in Bowman capsule
(physiological) .
21
22
GLOMERULAR FILTRATION RATE
APPLIED
 Kf can be reduced by pathological process e.g.
Diabetes mellitus, Hypertension, Glomerulonephritis
 If Kf decreased – decreased GFR – in hypertension,
diabetes mellitus, GMN, reduced Kf occurs due to
increased thickness of glomerular basement
membrane and damage to glomeruli.
23
24
AUTO-REGULATION MECHANISM
IN KIDNEY FOR GFR
 There is AUTOREGULATION mechanism in kidney
by which it maintains constant blood flow by
maintaining constant blood pressure.
 Autoregulation is done when systemic mean BP is in
the range of 80- 180 mmHg.
25
AUTO-REGULATION MECHANISM
IN KIDNEY FOR GFR
 If GFR increase due to increased BP, it will be reduced
to normal by constricting the afferent arteriole.
 If GFR decrease due to decreased BP, afferent arteriole
will be dilated to increase blood flow and bring GFR
back to normal.
26
AUTO-REGULATION MECHANISM
IN KIDNEY FOR GFR
 How kidneys maintain the constant BP ?
By altering the diameter of Afferent arteriole , there by
adjusting the flow to glomeruli .
 Auto regulation is done by TWO mechanism
1) Myogenic mechanism
2) Tubulo glomerular feed back mechanism.
We will study each one
27
AUTO-REGULATION MECHANISM
IN KIDNEY FOR GFR
1) Myogenic mechanism



Myogenic means muscle response.
Arterial vascular smooth muscle contracts in
response to stretch accompanying increased pressure
with in vessel, therefore, afferent arteriole constricts
and decreases blood flow.
But when BP decreases, there is relaxation of afferent
arteriole, therefore, increase blood flow occurs in the
glomerulus.
28
Myogenic Mechanism
Vascular smooth muscle contraction in response to increased stretch
Arterial
Pressure
Stretch of
Blood Vessel
Cell Ca++
Permeability
Blood Flow
Vascular
Resistance
Intracell. Ca++
(afferent arteriole)
29
AUTO-REGULATION MECHANISM
IN KIDNEY FOR GFR
2) Tubulo glomerular feed back mechanism
 It involves Juxta glomerular apparatus (formed by Afferent
and Efferent arteriole and DCT, Macula Densa Cells).
 So, if GFR increases due to increased BP, more fluid will
pass to DCT, therefore, increase Na+ delivery to DCT.
 In response to that Macula Densa cells release ATP and
Adenosine, both act locally by paracrine way and increase
calcium entry to afferent arteriole and cause constriction,
therefore, reducing glomerular blood flow and returning
GFR to normal.
30
IMPORTANCE OF AUTO
REGULATION
 As Myogenic and Tubulo glomerular feedback
mechanism work for auto regulation, therefore, they
prevent changes in GFR.
 If no auto regulation, changes in GFR will occur and
will lead to imbalance of fluid and electrolytes and
waste product excretion.
NOTE – If mean arterial BP is less than 80mmHg or
more than 180mmHg, auto regulation will NOT take
place and there will be changes in GFR.
31
BLOOD SUPPLY TO THE KIDNEY
 Kidney normally receives 20-25% of cardiac output i.e.
1.1 liter of blood flow per minute.
 About 625ml/min of plasma flows to the kidney.
 20% of plasma is filtered and converted to glomerular
filtrate and passes to Bowman’s Capsule, therefore,
average GFR is 125ml/min.
 The remaining [80%] of plasma passes to efferent arterioles
then into the peritubular capillaries
32
BLOOD SUPPLY TO THE KIDNEY
IMPORTANT POINTS
 Renal blood flow 1.1L (1100ml/min)
 Renal plasma flow 625ml/min
 GFR 125ml/min
 Kidney composes less than 1% of total body weight but
gets 20-25% cardiac output.
WHY? Because of its function i.e. regulating water ,
electrolyte balance and getting rid of waste products.
33
MEASUREMENT OF GFR
 Substances used to measure GFR
1. Inulin – polymer of fructose, it is filtered, but not
reabsorbed, not secreted by renal tubule
2. Creatinine – it is little secreted, therefore, not so
accurate as inulin.
Inspite of this clearance of endogenous creatinine is
frequently used to measure GFR
34
What is a Glomerular Filtration Fraction?
 The Filtration Fraction (FF) is the ratio of the GFR to
the renal plasma flow (GFR/RPF).
 Filtration fraction = GFR/Renal Plasma flow
= 125/625
= 0.2 = 20%
35
THANK YOU
36