Lecture No 15
GFR
Dr. Shaheen Haroon Rashid
Copyright © 2006 by Elsevier, Inc.
Nephron Tubular Segments
Figure 26-4;
Guyton and Hall
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Structure of
the juxtaglomerular
apparatus: macula
densa
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Figure 26-17;
Guyton and Hall
Objectives
• Discuss the processes involved in urine formation
• Define the term “GFR (Glomerular Filtration Rate)”
• Discuss the mechanism of glomerular filtration
• Describe the renal blood flow
• List the factors affecting GFR
• Discuss the auto regulation of GFR and renal blood flow
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The processes involved in urine
formation
• Filtration: Urine formation begins with filtration from the glomerular
capillaries into Bowman's capsule of a large amount of fluid that is
virtually free of protein. Most substances in the plasma, except for
proteins, are freely filtered so that their concentrations in the glomerular
filtrate in Bowman's capsule are almost the same as in the plasma.
•Reabsorption: The substance is freely filtered but is also partly
reabsorbed from the tubules back into the blood.
• Secretion: Certain foreign substances and drugs
are secreted from
the blood into the tubules, so that their excretion rates are high
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Renal Handling of
Different Substances
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Renal Handling of Water
and Solutes
Filtration Reabsorption
Water (liters/day)
Excretion
180
179
1
Sodium (mmol/day) 25,560
Glucose (gm/day)
180
Creatinine (gm/day)
1.8
25,410
0
0
150
180
1.8
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Basic Mechanisms
of Urine Formation
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Figure 26-8;
Guyton and Hall
• Urine formation begins with filtration from the glomerular
capillaries into Bowman's capsule of a large amount of fluid that
is virtually free of protein.
• Most substances in the plasma, except for proteins, are freely
filtered so that their concentrations in the glomerular filtrate in
Bowman's capsule are almost the same as in the plasma.
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Definition of “GFR
(Glomerular Filtration Rate)
Glomerular filtration rate, GFR, is the total amount of filtrate formed per
minute by both kidneys.
Normal value of GFR is125 ml/min
OR
180 L/DAY
Urine formation begins with glomerular filtration. it is a passive process in
which fluids and solutes are forced through the glomerular membrane
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Glomerular Capillary
Filtration Barrier
1. capillary endothelium - fenestrated
2. basement membrane homogeneous
glycoprotein/mucopolysaccharide
3. capsular epithelial cells, podocytes
& foot processes
the foot processes are covered with
glycosialoproteins which partially
occlude the slits
these are negatively charged, hence
present a charge-selective barrier
there are also extremely thin
diaphragms which bridge the slits at
the BM
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The Mechanism of Glomerular
Filtration
forces acting for glomerular filteration:
i.Glomerular hydrostatic pressure (PG )
ii.Bowman capsule hydrostatic pressure (PB )
iii.Colloid osmotic pressure of glomerular capillary
plasma proteins (πG )
iv.Colloid osmotic pressure of proteins in Bowman’s
capsule (πB )
Net filteration pressure=K f ×( PG - PB – πG + πB )
But πB is practically zero under normal conditions due
to absence of plasma proteins in the filterate.
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Factors effecting GFR
1. Renal blood flow: GFR is directly propotional to renal
plasma flow.
2. Size of capillary bed :contraction of mesangial cells
tends to distort capillary lumen and decreases
GFR.
3. Hydrostatic pressure in glomerular capillary (PG ):
i. Systemic blood pressure- is directly proportional to
systemic blood pressure when mean BP falls below
90mm Hg or rises above 220mm Hg. Between this
range GFR is stabilized by renal autoregulation range
is between 90-220 mmHg.
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ii. Afferent and efferent arteriolar constrictionconstriction of afferent arteriole reduces both renal
plasma flow and GFR. However constriction of
efferent arteriole has a biphasic effect on GFR. At a
moderate level of constriction of efferent arteriole
there is slight increase in GFR but with severe
constriction there is decrease in GFR.
4. Hydrostatic pressure in the bowman’s capsule (PB )
i. ureteral obstruction- increased (PB ) and decreased
GFR.
ii. Oedema of kidney inside tight renal capsuleincreased (PB ) and decreased GFR.
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Effect of Afferent and Efferent Arteriolar
Constriction on Glomerular Pressure
Ra
Re
PG
Blood Flow
Blood Flow
GFR
GFR
Ra
GFR +
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PG
Renal
Blood Flow
Re
GFR +
Renal
Blood Flow
5. Changes in concentration of plasma protein :
i. Hypoproteinemia – decreased capillary colloid
osmotic pressure (πG ) , increased GFR.
ii. Dehydration - increased capillary colloid osmotic
pressure (πG ) , decreased GFR.
6. State of glomerular (filtering)membrane :
The permeability of glomerular capillary membrane
is approx. 50 times that of capillaries in the
skeletal muscle.
Loss of negative charge of glomerular capillary
membrane results in proteinuria.
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Factors effecting GFR
• Molecular size ( small molecules > filterability)
• Ionic charge (cations > filterability)
• Age : GFR decreases with increasing age. This is due to
decrease in renal plasma flow, cardiac output and renal
tissue mass.
• Pregnancy: GFR elevated as much as 50% in first trimester
and onward; returns toward normal by 4 to 8 weeks
postpartum.
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Control of Glomerular Filtration
1. Sympathetic Nervous System
RA + R E
GFR + RBF
2. Catecholamines ( norepinephrine)
RA + R E
GFR + RBF
3. Angiotensin II
RE
GFR +
RBF
(prevents a decrease in GFR)
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Control of Glomerular Filtration
4. Prostaglandins
RA + R E
GFR +
RBF
5. Endothelial-Derived Nitric Oxide (EDRF)
RA + R E
GFR +
RBF
6. Endothelin
RA + R E
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GFR +
RBF
Control of Glomerular Filtration
7. Autoregulation of GFR and Renal Blood Flow
• Myogenic Mechanism
• Macula Densa Feedback
(tubuloglomerular feedback)
• Angiotensin II ( contributes to GFR but
not RBF autoregulation)
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Renal Autoregulation
120
Renal Artery
Pressure (mmHg)
100
80
Glomerular
Filtration Rate
Renal Blood
Flow
0
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1
2
3
Time (min)
4
5
Peculiarities of Ren. ciculation
• RBF more/high=1200ml/min.
• It is portal circulation
• Glomerular capillary hydrostatic pressure is
high=45mmHg(in others 25mmHg).
• It is autoregulated.
• A-V difference of O2 is low(3ml%).
• Secretion of enzymes& hormones( Renin,
Er,1,25DHCC, )
• Involed in homeostasis of water, electrolytes,pH
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Renal Blood Flow and GFR
Autoregulation
Figure 26-16;
Guyton and Hall
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AUTOREGULATION OF GFR AND RENAL
BLOOD FLOW
•
Feedback mechanisms intrinsic to the kidneys normally keep the renal
blood flow and GFR relatively constant, despite marked changes in arterial
blood pressure. These mechanisms still function in blood-perfused kidneys
thal have been removed from the body, independent of systemic
influences. This relative constancy of GFR and renal blood flow is referred
to as autoregulation.
•
The primary function of blood flow autoregulation in most other tissues
besides the kidneys is to maintain delivery of oxygen and nutrients to the
tissues at a normal level and to remove the waste products of metabolism,
despite changes in the arterial pressure. In the kidneys, the normal blood
flow is much higher than required for these functions. The major function
of autoregulation in the kidneys is to maintain a relatively constant GFR
and to allow precise control of renal excretion of water and solutes. The
GFR normally remains autoregulated (that is, remains relatively constant),
despite considerable arterial pressure fluctuations that occur during a
person's usual activities. In general, renal blood flow is autoregulated in
parallel with GFR, but GFR is more efficiently autoregulated under certain
conditions.
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Macula Densa Feedback
GFR
Distal NaCl
Delivery
Macula Densa NaCl Reabsorption
(macula densa feedback)
Afferent Arteriolar Resistance
GFR (return toward normal)
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Myogenic Mechanism
Arterial
Pressure
Stretch of
Blood Vessel
Cell Ca++
Permeability
Blood Flow
Vascular
Resistance
Intracell. Ca++
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Regulation of GFR by Ang II
GFR
Macula
Densa NaCl
Renin
Blood
Pressure
AngII
Efferent Arteriolar
Resistance
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Macula densa
feedback
mechanism
for GFR
autoregulation
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Figure 26-18;
Guyton and Hall
Clearance
• Clearance is a general concept that describes the
rate at which substances are removed (cleared)
from the plasma.
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Clearance Technique
Renal clearance of a substance is the volume of
plasma completely cleared of a substance per min.
Where:
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Cs x Ps = Us x V
Cs
= Us x V
Ps
Cs = clearance of substance S
Ps = plasma conc. of substance S
Us = urine conc. of substance S
V = urine flow rate
Use of Clearance to Measure GFR
For a substance that is freely filtered, but not reabsorbed or
secreted (inulin, 125 I-iothalamate, ~creatinine), renal clearance
is equal to GFR
amount filtered = amount excreted
GFR x Pin
=
GFR =
Uin x V
Uin x V
Pin
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Calculate the GFR from the following data:
Pinulin = 1.0 mg / 100ml
Uinulin = 125 mg/100 ml
Urine flow rate = 1.0 ml/min
U
x
V
in
GFR = Cinulin =
Pin
GFR =
125 x 1.0
1.0
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= 125 ml/min
Thank You
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