Nephron:
functional unit of
the kidney
Copyright © 2006 by Elsevier, Inc.
Figure 26-3;
Guyton and Hall
Nephron Tubular Segments
Figure 26-4;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
Structure of
the juxtaglomerular
apparatus: macula
densa
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Figure 26-17;
Guyton and Hall
Cortical and Juxtamedullary
Nephron Segments
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Figure 26-5;
Guyton and Hall
• http://www.youtube.com/watch?v=glu0dz
K4dbU
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Summary of Kidney Functions
• Excretion of metabolic waste products: urea,
creatinine, bilirubin, hydrogen
• Excretion of foreign chemicals: drugs, toxins,
pesticides, food additives
• Secretion, metabolism, and excretion of hormones
- renal erythropoetic factor
- 1,25 dihydroxycholecalciferol (Vitamin D)
- Renin
• Regulation of acid-base balance
• Gluconeogenesis: glucose synthesis from amino
acids
• Control of arterial pressure
• Regulation of water & electrolyte excretion
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Basic Mechanisms
of Urine Formation
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Figure 26-8;
Guyton and Hall
Renal Handling of
Different Substances
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Figure 26-9;
Guyton and Hall
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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Glomerular
Capillary Filtration
Barrier
Figure 26-10;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
The Ability of a Solute to Penetrate the
Glomerular Membrane Depends on:
• Molecular size ( small molecules > filterability)
• Ionic charge (cations > filterability)
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Effects of Size and Electrical Charge of
Dextran on Filterability by Glomerular
Capillaries
Figure 26-11;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
Clinical Significance of
Proteinuria
• Early detection of renal disease in at-risk patients
- hypertension: hypertensive renal disease
- diabetes: diabetic nephropathy
- pregnancy: gestational proteinuric hypertension (preeclampsia)
- annual “check-up”: renal disease can be silent
• Assessment and monitoring of known renal disease
• “Is the dipstick OK?”: dipstick protein tests are not
very sensitive and not accurate: “trace” results can be
normal & positives must be confirmed by quantitative
laboratory test.
Copyright © 2006 by Elsevier, Inc.
Figure 26-12;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
Glomerular Hydrostatic
Pressure (PG)
• Is the determinant of GFR most subject
to physiological control
• Factors that influence PG
- arterial pressure (effect is buffered by autoregulation)
- afferent arteriolar resistance
- efferent arteriolar resistance
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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
Effect of changes
in afferent
arteriolar or
efferent arteriolar
resistance
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Figure 26-14;
Guyton and Hall
determined by : FF = GFR / RPF
G
RBF
GFR
RE
+
PG
Copyright © 2006 by Elsevier, Inc.
_
Summary of
Determinants of GFR
Kf
PB
G
GFR
GFR
GFR
A
FF
PG
GFR
PG
PG
GFR
GFR
GFR
RA
RE
(as long as
Copyright © 2006 by Elsevier, Inc.
G
G
RE < 3-4 x normal)
Assessing Kidney Function
• Albumin excretion (microalbuminuria)
• Plasma concentration of waste products
(e.g. BUN, creatinine)
• Urine specific gravity, urine concentrating ability
• Imaging methods (e.g. MRI, PET, arteriograms,
iv pyelography, ultrasound etc)
• Isotope renal scans
• Biopsy
• Clearance methods (e.g. 24-hr creatinine clearance)
• etc
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Clearance
• Clearance is a general concept that describes the
rate at which substances are removed (cleared)
from the plasma.
Copyright © 2006 by Elsevier, Inc.
Clearance Technique
Renal clearance of a substance is the volume of
plasma completely cleared of a substance per min.
Where:
Copyright © 2006 by Elsevier, Inc.
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
Copyright © 2006 by Elsevier, Inc.
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
Steady-state
relationship
between
GFR and serum
creatinine
concentration
Figure 27-19;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
Clearances of Different
Substances
Substance
inulin
glucose
sodium
urea
Clearance (ml/min)
125
0
0.9
70
Clearance of inulin (Cin) = GFR
if Cx < Cin: indicates reabsorption of x
if Cx > Cin: indicates secretion of x
Clearance creatinine (Ccreat) ~ 140 (used to estimate GFR)
Copyright © 2006 by Elsevier, Inc.
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)
Copyright © 2006 by Elsevier, Inc.
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
Renal Blood Flow and GFR
Autoregulation
Figure 26-16;
Guyton and Hall
Copyright © 2006 by Elsevier, Inc.
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