Lisa M. Harrison-Bernard, PhD
4/20/2011
Renal Physiology 2011
Lisa M. Harrison-Bernard, PhD
Contact me at lharris@lsuhsc.edu
Renal Physiology Lecture 3
Renal Clearance and Glomerular Filtration
Filtration and Reabsorption
Amount
Filter/d
Amount
%
Excrete/d Reabsorb
Water (L)
180
1.8
99.0
K+ (mEq)
720
100
86 1
86.1
Ca2+ (mEq)
540
10
98.2
HCO3(mEq)
4,320
2
99.9+
Cl- ((mEq)
q)
18,000
,
150
99.2
Na+ (g)
630
3.2
99.5
Glucose (g)
180
0
100
Urea (g)
54
30
44
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Tubular Secretion
Most important:
• H+
• K+
• Organic anions
choline
creatinine
• Foreign chemicals
penicillin
Handling of Substance L
by Kidney
• Filtered Load
GFR X Plasma [L]
GFR • PL
• Excretion Rate
Urine [L] X Urine flow
•
UL • V
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Summary
1. Kidney is a very
important organ.
2 Juxtaglomerular
2.
apparatus is coolest.
3. 3 basic renal processes
• Filtration, reabsorption,
secretion
4. Damage to filtration
barrier results in
glomerular disease
Renal Physiology - Lectures


3.
4.
5.
6.
Physiology of Body Fluids
Structure & Function of the Kidneys
Renal Clearance & Glomerular Filtration
Regulation of Renal Blood Flow
Transport of Sodium & Chloride
Transport of Urea, Glucose, Phosphate, Calcium
& Organic Solutes
7. Regulation of Potassium Balance
8. Regulation of Water Balance
9. Transport of Acids & Bases
10. Integration of Salt & Water Balance
11. Clinical Correlation – Dr. Credo
12. PROBLEM SET REVIEW – May 9, 2011
13. EXAM REVIEW – May 9, 2011
14. EXAM IV – May 12, 2011
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Renal Physiology Lecture 3
Renal Clearance and Glomerular Filtration
Chapter 3 Koeppen & Stanton Renal Physiology
1. Starling Forces
2. Control of GFR
3. Concept of Renal Clearance
4 Clearance of Inulin & Creatinine
4.
= Estimates of GFR
5. PAH = Estimate of RPF
Fluid Movement Out of Glom Cap –
Into Bowman’s Space
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Glomerular Ultrafiltration - Eq 3-10
Starling
g Forces (J
( v)
=
Kf [(PGC-PBS) - σ(GC-BS)]
Jv – volume flux across the capillary wall
Glomerular Ultrafiltration - Eq 3-10
GFR
=
Kf [(PGC-PBS) - σ(GC-BS)]
σ – reflection coefficient for protein
=1
protein cannot cross
glomerular membrane
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Kf – Ultrafiltration Coefficient
GFR = Kf [(PGC-PBS) - (GC-BS)]
Kf ml/min/mmHg
• Intrinsic permeability glom
capillary
• Product of hydraulic conductivity
(Lp) & surface area (Sf)
• Lp & Sf 10-100 X > other beds
Kf – Ultrafiltration Coefficient
Kf = Lp x A
A - cm2
• Area - total capillary surface area
• ~ 1 cm length/glom cap
• ~ 12 miles total length (2 mil glom)
• 6,000
6 000 cm2 total
t t l surface
f
area
• filtration area ~10% (Fenestrae)
Boyle et al. Kidney International 1998
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Ultrafiltration Coefficient
GFR = Kf (PUF)
Kf ml/min/mmHg
125 ml/min =
8.3 ml/min/mmHg (15 mmHg)
Forces Involved in Glomerular Filtration – Fig 3-6
Efferent
Arteriole
Afferent
A
Arteriole
l
Bowman’s
space
PGC GC
2 forces favor
fluid filtration
2 forces oppose
fluid filtration
BS
LSU Medical Physiology 2010
PBS
7
Lisa M. Harrison-Bernard, PhD
4/20/2011
Forces Involved in Glomerular Filtration – Fig 3-6
Efferent
arteriole
Afferent
arteriole
Bowman’ss
Bowman
space
PGC GC
Two forces oppose
fluid filtration.
Two forces favor
fluid filtration.
BS
PBS
PGC = Glomerular capillary hydrostatic pressure
BS = Bowman’s space oncotic pressure
PBS = Bowman’s space hydrostatic pressure
GC = Glomerular capillary oncotic pressure
Net Filtration Pressure = PGC – PBS – GC + BS
Forces Involved in Glomerular Filtration
Net glomerular filtration
pressure
= PGC – PBS – GC + BS
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Net Glomerular Filtration PressureGlomerular Capillary
= PGC – PBS – GC + BS
PGC= 50, PBS= 10,  GC= 25,  BS= 0 mmHg
50 - 10 - 25 + 0 mmHg = 15 mmHg
PGC – only force favors filtration
2X > most capillaries
Glomerular Ultrafiltration - Eq 3-10
GFR = Kf [(PGC-PBS) - (GC-BS)]
PUF
Rate of glomerular ultrafiltration
=
ultrafiltration coefficient (Kf) X
net Starling forces (PUF)
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Starling Forces Change Along the Length of
Capillaries: Skeletal Muscle (Non-Renal Capillary)
Arteriole
Venule
Net Absorption
Net Filtration
Equilibration Point
Overall: Filtration ~ Absorption
Starling Forces Along Glomerular Capillaries
47
35
35
10
10
Afferent
arteriole
Distance along glom
cap network
Efferent
arteriole
 GC increases along glom capillary
NEVER Absorptive flux
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Forces Involved in ABSORPTION
by Peritubular Capillaries
Net peritubular capillary pressure
=
PPC – PO – PC +  O
PO
O
PPC
 PC
Net Glomerular Filtration PressurePeritubular Capillary
= PPC
– PO – PC +  O
PPC = 20, PO = 8,  PC = 35,  O = 6 mmHg
20 - 8 – 35 + 6 mmHg = minus 17 mmHg
Negative filtration ≡ absorption
Forces favor reabsorption of fluid
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Renal Physiology Lecture 3
 Starlingg Forces
2. Control of GFR
3. Concept of Renal Clearance
4 Clearance of Inulin & Creatinine
4.
5. Clearance of PAH
What would
happen to
GFR if
↑ RAP?
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Control of GFR
PUF = PGC – PBS – (GC – BS)
GFR = Kf (PUF)
•  Renal Artery Pressure (RAP) =
 PGC =  GFR
EA
•  AA resistance
 PGC =  GFR
GC
AA
Control of GFR
PUF = PGC – PBS – (GC – BS)
GFR = Kf (PUF)
•  AA resistance
EA
GC
 PGC =  GFR
•  EA resistance
AA
 PGC =  GFR
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Control of GFR
PUF = PGC – PBS – (GC – BS)
GFR = Kf (PUF)
•  GC -  GFR
—
—
 protein metabolism malnutrition, hepatic disease, GI
losses
 protein excretion - kidney
disease = proteinuria
Control of GFR
PUF = PGC – PBS – (GC – BS)
GFR = Kf (PUF)
•  PBS -  GFR
acute obstruction – stone,
enlarged prostate
•  BS -  GFR
filter protein - proteinuria
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Control of GFR
PUF = PGC – PBS – (GC – BS)
GFR = Kf (PUF)
Kf = Lp x Sf
•  Kf =  GFR
reduce surface area or # filtering
glomeruli
– hypertension
h
t
i
– diabetes
– glomerulosclerosis
Decreases in GFR - Disease
GFR = Kf [(PGC-PBS) - (GC-BS)]
• Acute Renal Failure
 RAP,  RA,  RE,  PG,  GFR
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Renal Physiology Lecture 3
 Starlingg Forces
 Control of GFR
3. Concept of Renal Clearance
4 Clearance of Inulin & Creatinine
4.
5. Clearance of PAH
Renal Plasma Clearance
•
Renal CLEARANCE of any substance
volume of plasma from which a
substance is completely removed
(cleared) by kidneys per unit time
Units = Volume plasma per time
ml/min
l/ i
•
QUANTITATIVE evaluation: how kidney
handles specific substance
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Clearance S =
Mass S excreted / time
Plasma [S]
•
ClS • PS = US • V
•
ClS = US • V
PS
What is the
renall
clearance of
glucose?
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Substance
CLEARANCE
(ml/min)
Glucose
0
Na+
0.9
K+
12
Inulin
125
Creatinine
140
PAH
560
Renal Physiology Lecture 3
 Starling Forces
 Control of GFR
 Concept of Renal Clearance
4 Clearance of Inulin & Creatinine
4.
5. Clearance of PAH
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Inulin
ClIN = GFR
Inulin
PIN X GFR
=
.
UIN X V
LSU Medical Physiology 2010
•
•
•
•
•
•
•
•
•
MW 5,000 Da
Freely filterable
NOT reabsorbed
NOT secreted
NOT metabolized,
synthesized, stored
NOT alter GFR
NONtoxic
Infusion required
PIN ,UIN - analytic
method
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Inulin
Measurement of GFR
Amount Filtered = Amount Excreted
•
GFR · PIN = UIN · V
•
GFR = UIN · V = ClIN
PIN
Creatinine
ClCr ~ GFR
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Creatinine
Rate of Production = Rate of Excretion
1 g/day = 1 g/day
Index of GFR
•
GFR (ClearanceCr) = UCr • V
PCr
ClCr is inversely related to PCr
Creatinine ~Fig 3-2
PCr X GFR
=
.
UCr X V
LSU Medical Physiology 2010
•
Metabolism of creatine
phosphate - muscle
•
•
•
•
•
•
•
Produced continuously
y
Freely filtered
NOT reabsorbed
Small amount secreted
NO infusion required
Stable P[Cr]
P[Cr] & U[Cr] –
colorimetric method
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Lisa M. Harrison-Bernard, PhD
4/20/2011
PlasmaCr Inversely Related to GFR ~Fig 3-3
PCr = 6mg/dl
6 /dl
GFR 1/6
PCr=2mg/dl
GFR ½
Normall
N
PCr=1mg/dl
Normal GFR
Plasma Creatinine Concentrations
PCr = 0.8 – 1.2 mg/dl (1.0mg/dl)
normal range for adult
PlasmaCr inversely related to GFR
GFR
ml/min
120
60
30
15
LSU Medical Physiology 2010
PCr
mg/dl
1
2
4
8
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Normal Values GFR
GFR corrected to body
surface area 1.73 m2
• Newborns 20 ml/min
• ♀ 120 ml/min
•
♂
130 ml/min
Declines after age 40
• ~ 1 ml/min/yr
Current Recommendations for Routine
Estimation of GFR in Clinical Setting
MDRD Study Equation:
GFR (ml/min/1
(ml/min/1.73
73 m2) =
175 X (SCr)-1.154 X (Age)-0.203 X (0.742 if female) X (1.212 if African American)
Cockcroft-Gault Equation:
Clearance Cr (ml/min) =
(140 – age) X (Wt in kg) X (0.85 if female) / (72 X SCr)
MDRD = Modification of Diet in Renal Disease; SCr = serum creatinine, mg/dl
GFR Calculators Are Available Online:
National Kidney Disease Education Program (NKDEP) of NIH
Kidney Disease Outcomes Quality Initiative (KDOQI) of National Kidney Foundation
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Renal Physiology Lecture 3
 Starling Forces
 Control of GFR
 Concept of Clearance
 Clearance of Inulin & Creatinine
5. Clearance of PAH
PAH
P
Para-amino
i
hippuric acid
ClPAH ~ RPF
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Para-amino hippuric acid (PAH)
•
•
•
•
•
•
•
Organic anion
Freely filtered
Vigorously secreted PT
 90% removed single
circuit
~ 10%
% RV
NOT produced
Infusion required
Para-amino hippuric acid (PAH)
PAH Clearance ~ Renal Plasma Flow
Amount Entering Kidney ~ Excretion Rate
•
RPF • PPAH = UPAH • V
Rearrange
•
RPF = UPAH • V
PPAH
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Summary
1. Glomerular filtrate
formation -filtration
barrier & Starling forces
2. Clearance of certain
substances – index of
renal function
3. Plasma creatinine - tool
for diagnosing and
following renal function
THE END
LSU Medical Physiology 2010
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Lisa M. Harrison-Bernard, PhD
4/20/2011
Calculate Renal Plasma Flow
•
PPAH = 0.05 mg/ml; UPAH = 30 mg/ml; V = 1.0 ml/min
•
RPF = UPAH • V
PPAH
R ‘Plasma’ F = RPF = 600 ml/min
0.50 Hct
R ‘Blood’ F = RBF = 1,200 ml/min
Review Clearance Principles
•
•
•
•
•
•
ClX < GFR net reabsorption X
ClX > GFR net secretion X
ClX < ClIN reabsorbed - glucose
ClX > ClIN secreted - PAH
ClX = ClIN only filtered - creatinine
filtered load > rate of excretion =
reabsorption X
LSU Medical Physiology 2010
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