Renal Blood Flow
GFR
¾ Blood flow to kidney about 1,100 ml/min (plasma
600ml/min)
¾ Glomerular filtration rate:
about 120 ml /minute (180 L a day)
¾ Decreases with age (about 10 ml/min for each decade
over 40)
¾ GFR = Sum of the filtration of two million glomeruli
¾ Each glomerulus probably filters about 20 nl/min
(ie total GFR divided by number of nephrons)
¾ 20% of resting cardiac output is directed to the
kidneys
¾ If GFR is 120ml/min and plasma flow is 600ml/min
then 20% of every mm of plasma passing the
glomeruli is diverted into the tubular system as
filtrate
¾ Ratio of GFR to renal plasma flow is 0.2 and is called
the filtration fraction
Blood in
Blood out
Renal Blood Flow (cont’d)
¾ Blood flow to kidneys is kept constant as it is not
dependent on metabolic demands
Capillaries
(vasa recta)
¾ Regulation of RBF is designed to sustain high
filtration rates not metabolic rates
¾ High RBF (low renal vasculature resistance) is due to
low resting sympathetic nervous tone and high
production of the vasodilator nitric oxide
To venous
system
¾ In pregnancy RBF and GFR are increased (30% 50%). Due to elevated cardiac output and to enhanced
renal nitric oxide production
Urine formation
Glomerulus Fluid Flow and Forces
Blood in
Blood out
¾Glomerulus capillary hydrostatic pressure is
higher than pressure in other capillaries
because of the presence of the efferent
arteriole which exerts a post-capillary
resistance
Capillaries
(vasa recta)
To venous
system
Urine formation
1
Regulation of GFR
Structural changes
¾ Renal hypertrophy causes an increase in GFR
¾Changes in GFR can occur from
¾ When one kidney is removed, either due to disease or
to donate, the other kidney undergoes a growth of
both blood vessels and tubules (hypertrophy), ie
nephrons grow
ƒ Structural changes
ƒ Changes in filtration pressure
¾ Hypertrophy is usually complete in 4 weeks, and the
GFR has returned to normal ie the remaining kidney
has doubled its GFR without increasing the number
of nephrons.
Changes in Filtration Pressure
Capillaries
(vasa recta)
¾ Changes in afferent arteriole resistance is the most
common physiological regulator of GFR
¾ Increase in afferent resistance (ie vasoconstriction)
decreases GFR
Urine formation
Changes in Filtration Pressure
Less Blood in
Capillaries
(vasa recta)
Less Filtrate
¾ Changes in afferent arteriole resistance is the most
common physiological regulator of GFR
¾ Increase in afferent resistance (ie vasoconstriction)
decreases GFR
¾ Decrease in afferent resistance (vasodilation)
increases GFR
Urine formation
2
Changes in Filtration Pressure
More Blood in
¾ Changes in afferent arteriole resistance is the most
common physiological regulator of GFR
Capillaries
(vasa recta)
More Filtrate
Urine formation
¾ Increase in afferent resistance (ie vasoconstriction)
decreases GFR
¾ Decrease in afferent resistance (vasodilation)
increases GFR
¾ Arteriole tone (ie contraction or dilation) can be due
to presence of vasoactive agents, eg angiotensin,
nitric oxide; or due to changes in sympathetic tone
(epinephrine and norpeinephrine)
Changes in Filtration Pressure
Blood in
Less blood out
¾ Changes in efferent arteriole resistance
Capillaries
(vasa recta)
¾ Vasoconstriction of the efferent arteriole increases the
hydrostatic pressure in the capillaries of the
glomerulus as it acts like a dam, and GFR increases
More Filtrate
Urine formation
Changes in Filtration Pressure
Blood in
More blood out
¾ Changes in efferent arteriole resistance
¾ Vasoconstriction of the efferent arteriole increases the
hydrostatic pressure in the capillaries of the
glomerulus as it acts like a dam, and GFR increases
Capillaries
(vasa recta)
Less Filtrate
¾ Dilation of the efferent arteriole decreases glomerular
capillary hydrostatic pressure, therefore GFR
decreases
Urine formation
3
Renal obstructions
Blood in
Blood out
• These tend to decrease GFR, as a blockage in a renal
tubule exerts a pressure back on the glomerulus that
reduces filtration
Capillaries
(vasa recta)
Less Filtrate
• Obstruction can be due to cell necrosis, or lower
urinary tract blockage e.g. kidney stone, which blocks
urine flow
To venous
system
Urine formation
Autoregulation of GFR
¾ Afferent arteriole resistance when altered changes
GFR. However, usually the changes in resistance are
a compensation so that GFR remains constant
Arterial Pressure
¾ Decreases in arterial pressure causes less blood flow
to the renal artery, but GFR remains constant as the
afferent arteriole compensates by vasodilating
(resistance decreases) keeping blood flow to the
gomerulus constant
¾ A change in arterial pressure is the most common
perturbation associated with autoregulation of GFR
Arterial Pressure
Capillaries
(vasa recta)
¾ Decreases in arterial pressure causes less blood flow
to the renal artery, but GFR remains constant as the
afferent arteriole compensates by vasodilating
(resistance decreases) keeping blood flow to the
gomerulus constant
¾ Conversely, if arterial pressure increases, the afferent
arteriole constricts (resistance increases) so that the
increase in arterial pressure is not transmitted to the
glomerulus and GFR remains constant
¾ Range of autoregulation is an arterial pressure of
between 80-180 mm Hg
Urine formation
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Mechanisms of Alterations in
Afferent Arteriole Resistance
¾ Myogenic : smooth muscle changes in the arteriole,
smooth muscle will contract when wall tension
increases
Tubuloglomerular feedback
¾ This is the term for a circuit designed to keep NaCl
concentrations at the macula densa, and therefore,
concentrations of Na that enter the collecting duct,
constant.
¾ Tubuloglomerular feedback : signal comes from the
renal tubule (nephron)
Conservation of sodium by the different segments of the
nephron
MACULA DENSA
Proximal tubule
67%
16,800 mEq/day
Thick ascending limb
25%
6300 mEq/day
Distal tubule
5%
1260 mEq/day
Collecting duct
3%
750 mEq/day
Tubuloglomerular feedback (cont’d)
¾ Increased NaCl concentration at the macula densa
causes afferent arteriole to constrict, which leads to
less pressure for filtration, so GFR decreases
This decline in GFR now limits how much Na
reaches the macula densa, and how much is delivered
to the distal nephron (equilibrium is maintained)
Tubuloglomerular feedback
¾ This is the term for a circuit designed to keep NaCl
concentrations at the macula densa, and therefore,
concentrations of Na that enter the collecting duct,
constant.
¾ NaCl concentration at the macula densa can control
the tone of the afferent arteriole, and therefore
controls GFR.
Conservation of sodium by the different segments of the
nephron
MACULA DENSA
Proximal tubule
67%
16,800 mEq/day
Thick ascending limb
25%
6300 mEq/day
Distal tubule
5%
1260 mEq/day
Collecting duct
3%
750 mEq/day
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Tubuloglomerular feedback (cont’d)
Clinical Considerations
¾ Increased NaCl concentration at the macula densa
causes afferent arteriole to constrict, which leads to
less pressure for filtration, so GFR decreases
This decline in GFR now limits how much Na
reaches the macula densa, and how much is delivered
to the distal nephron (equilibrium is maintained)
¾ Autoregulation response serves to protect the
glomerulus from elevated blood pressure (arterial
pressure)
¾ Decreased NaCl concentration at the macula densa
causes afferent arteriole to relax (vasodilate) so more
blood enters as less resistance, so pressure for
filtration increases, and GFR increases
Hypertension
(sustained high blood pressure)
has to caused by a defect in renal function (loss
of autoregulation) and not due to changes in
vasculature (eg cardiac output, peripheral
resistance etc)
¾ Constant high blood pressure is associated with the
development of pathology in the glomerular structure
and function, and autoregulation is lost
Diabetes
¾Diabetes in its early stage causes dilation
of afferent arteriole (glucose is high in
plasma) and results in an increase in the
glomerular capillary pressure, which
contributes to the glomerular damage in
these patients
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