Lisa M Harrison-Bernard, PhD
4/19/2011
Renal Physiology 2011
Lisa M. Harrison-Bernard, PhD
lharris@lsuhsc.edu
Renal Physiology - Lectures

2.
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
4/19/2011
How Many Students
Have Studied the Kidney:
Anatomy?
Histology?
Physiology?
How to Approach Renal Physiology?
Gross
Anatomy
+
+ Respiratory
Physiology
LSU Medical Physiology 2010
Histology
CV
Clinical
+
+Medicine
Physiology
Endocrine
+Physiology
GI
+
Physiology
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Lisa M Harrison-Bernard, PhD
4/19/2011
APPENDIX
A. Integrative Case Studies
B. Normal Laboratory Values
C. Nephron Function
• Transport Processes
• Nephron Segment
D. Answers to Self Study Problems
WHY Does a Medical Student
Need to Learn Renal Physiology?
• 23 million adult patients – kidney
•
•
•
•
•
•
LSU Medical Physiology 2010
disease
90,000 deaths/yr
530,000 ESRD/yr
370,000 hemodialysis/peritoneal
dialysis
18,000 kidney transplants/yr & 86,000
waiting
ESRD $35 billion/yr
9th leading cause of death
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Lisa M Harrison-Bernard, PhD
4/19/2011
WHAT Does a Nephrologist Expect
a Medical Student to Know?
1) What is GFR?
•
How is it determined?
•
How is it estimated?
2) Body Fluid Compartments
g
of Sodium &
3)) Regulation
Water Balance
4) Potassium Homeostasis
5) Acid/Base Physiology
Renal Physiology Lecture 2
Structure and Function of the Kidneys
Reading Assignment:
Chapter 2 Koeppen & Stanton Renal
Physiology
LSU Medical Physiology 2010
1.
Function
2.
Review Anatomy
3.
Juxtaglomerular Apparatus
4.
Filtration Barrier
5.
Basic Renal Processes
4
Lisa M Harrison-Bernard, PhD
4/19/2011
Which is most important in
regulating water balance?
a) Water lost through
skin and lungs
b) Water lost in feces
c) Water lost in sweat
d) Urine production
Correct answer d)
What are
the
functions of
the
kidney???
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Functions of Kidney
Major regulation of
body water &
inorganic ions =
ECF
Regulate body fluid
•
osmolality
•
volume
Functions of Kidney
• Regulate water & inorganicion balance ≡ BP
H2O, Na+, K+, Ca2+, Cl-,
Mg2+, etc.
• Acid-base balance
• Eliminate metabolic waste
aste
products
Urea, uric acid, creatinine
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Functions of Kidney
• Eliminate foreign
compounds
Drugs, toxins, pesticides
• Gluconeogenesis
• Secrete hormones
Erythropoietin
Renin
1,25-dihydroxy Vitamin D3
** Renal Failure Patient **
Patient Data
 Normal
PlasmaK+

PUrea

BP

PPO4-

Hematocrit

PHCO3-

PpH

PCa2+

LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Renal Physiology Lecture 2
 Function
2.
REVIEW ANATOMY
3.
Juxtaglomerular
pp
Apparatus
4.
Filtration Barrier
5.
Basic Renal Processes
Basic Anatomical Structure of Kidneys
Retroperitoneal
12th thoracic3rd lumbar
vertebrae
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Section of Human Kidney ~ Fig 2-1
Functional
unit of
kidney
800,000 –
1,200,000
nephrons/
kidney
Venous
Arterial
Vessels & Capillaries Vessels
Tubules
Peritubular
Capillaries
Medullary
Capillary
Plexus
Kriz, 1991
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Structure of Nephron ~ Fig 2-2
DCT
JMN
AA
Cortex
Bowman’s
PCT
PST
Medulla
TAL
tDLH
tALH
Important Characteristics of Renal Vasculature ~ Fig 2-2
Virtually ALL blood
entering kidney flows
g glomeruli
g
- ALL
through
located in cortex!
2 capillary beds in sequence:
Glomerular
capillaries
Postglomerular
capillaries
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Important Characteristics of Renal Vasculature ~ Fig 2-2
2 types postglomerular
capillaries:
Cortex - Peritubular
capillaries
ill i
Medulla - Vasa recta
Inflow & outflow vessels
of glomerular capillaries
are arterioles:
Inflow - Afferent
arteriole
Outflow - Efferent
arteriole (exit)
Scanning EM - Renal Vasculature ~ Fig 2-6
Afferent
Arteriole
Glomerulus
Artery
Courtesy of Kate Denton Ph.D., Monash University
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Scanning EM – Glomerulus Between Afferent
and Efferent Arterioles ~ Fig 2-6
PC – Peritubular Capillary
EA – Efferent Arteriole
Glomerular Capillary
AA – Afferent Arteriole
Scanning EM – Podocytes ~ Fig 2-8
Podocyte
‘cells with feet’
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Distribution of Blood Flow
CO = 5 L/min
20%
% off CO
RBF = 1 L/min
Cortex – 90%
Medulla – 10%
Renal Physiology Lecture 2
 Function
 Review Anatomy
LSU Medical Physiology 2010
3.
JUXTAGLOMERULAR
APPARATUS
4.
Filtration Barrier
5.
Basic Renal Processes
13
Lisa M Harrison-Bernard, PhD
4/19/2011
Juxtaglomerular Apparatus ~ Fig 2-5
2.
1.
1. Juxtaglomerular
Cells of afferent
arteriole
3.
2. Macula Densa
Cells of thick
ascending limb
of loop of Henle
(TAL, spot dark)
3. Extraglomerular
Mesangial Cells
Juxtaglomerular Apparatus
Communication
between TAL
of loop &
afferent
arteriole of
same nephron
LSU Medical Physiology 2010
Afferent
arteriole
Macula
densa
cells,TAL
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Lisa M Harrison-Bernard, PhD
4/19/2011
Renal Physiology Lecture 2
 Function
 Review Anatomy
 Juxtaglomerular
pp
Apparatus
4.
FILTRATION BARRIER
5.
Basic Renal Processes
Filtration Barrier
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Filtration Barrier ~ Fig 2-7
1. Capillary
Endothelium
} with
Fenestrations
RBC
Capillary Lumen
2. Glomerular
Basement
Membrane
Urinary Space
3. Podocyte with
Filtration Slit
Diaphragm
Filtration Barrier – Fig 2-7,8
1. Endothelium –
fenestrations (windows)
• 70 nm holes – limit filtration
of cellular elements – RBC
WBC, platelets
2. Basement Membrane –
“prefilter”
• Barrier to protein
• Charge selective filter
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Filtration Barrier ~ Fig 2-8
3. Podocyte with Filtration
Slit Diaphragm – “size
selective filter”
• 4-14 nm pores, negative
charged glycoproteins
NEGATIVELY charged glycoproteins on
surfaces ALL components of glomerular
filtration barrier
Filtration Slit Diaphragm ~ Fig 2-9
Podocin Nephrin
Podocyte
NEPH-1
Podocyte
GBM
Mutations in Nephrin, NEPH-1, Podocin
= Proteinuria = Nephrotic Syndrome
LSU Medical Physiology 2010
Endo
17
Lisa M Harrison-Bernard, PhD
4/19/2011
What would
happen if
negative
charges were
obliterated?
Causes of Glomerular Disease
• Albumin – primary plasma
protein – NORMALLY too large
filtered (69 kDa)
— charged
• Alter size and/or chargeselective properties of filtration
barrier =
Proteinuria – protein in urine earliest sign and hallmark of
renal disease
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Clinical Examples of Glomerular Pathology
•
Endothelium
swell
•
Basementt membrane
B
b
thickens
diabetes
•
Podocyctes foot processes
fuse – reduce filtration
increased pore size proteinuria
Clinical Examples of Glomerular Disease
• Loss of negative charge on
membranes
secondary to
immunological damage
and inflammation
filter albumin – proteinuria
p
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Glomerular Filtrate
• Water only enters nephron by
filtration
• 1st step in urine formation
• Electrolytes freely filtered
Glom conc = Plasma conc
• Macromolecules not filtered
• <10,000 MW filtered
Glomerular Filtrate
• Net glomerular filtration
pressure initiates urine
f
formation:
ti
• forcing cell-free, essentially
protein-free filtrate of plasma
• driven by Starling’s forces
• out of glomeruli into
Bowman’s space
• down tubule into renal pelvis
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Renal Physiology Lecture 2




Function
5.
BASIC RENAL PROCESSES
Review Anatomy
Juxtaglomerular Apparatus
Filtration Barrier
Luminal
section of
plasma
membrane of
tubule cells
faces filtrate
Basolateral
section in
close
l
proximity
to peritubular
capillary
(blood side)
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Renal Processes
1. Filtration
Glomerular capillary lumen 
Bowman’s space (bulk flow)
2. Tubular Reabsorption
Tubular lumen  peritubular
capillary plasma
3. Tubular Secretion
Peritubular plasma (capillary
lumen)  interstitial space
 tubular cell  tubular
lumen (tubular cell interior to
tubular lumen)
Basic Renal Processes
A
Amount
tE
Excreted
t d in
i Urine
Ui
= Amount Filtered + Amount
Secreted – Amount Reabsorbed
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Glomerular Filtration
• Net filtration of fluid across all
capillaries (except kidney)
= 4 L/d
• Glomerular Filtration Rate - GFR
= 125 ml/min (both kidneys)
= 180 L/day
• Plasma volume - PV
= 3 L = filtered 60X /d
• ECFV
= 17 L = filtered 10X /d
Tubular Reabsorption
• Small % filtered
amounts excreted
tubules reabsorb into
body HUGE amounts
fluid & solutes
• > 99% volume filtered
(GFR) reabsorbed
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
Tubular Reabsorption
• Filtered Load
> Excretion Rate
Net reabsorption of substance
• Filtered Load
NaCl = 3 - 4 # / d
Glucose = 1/2 # / d
REABSORPTION IS IMPERATIVE!!
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
4/19/2011
Tubular Secretion
Most important:
• H+
• K+
• Organic anions
choline
creatinine
• Foreign chemicals
penicillin
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
LSU Medical Physiology 2010
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Lisa M Harrison-Bernard, PhD
4/19/2011
THE END
LSU Medical Physiology 2010
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