Renal Hemodyn Lec 1-HX
description
Transcript of Renal Hemodyn Lec 1-HX
![Page 1: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/1.jpg)
Regulation of Renal Hemodynamics and GFR
L. Gabriel Navar, Ph.D.Department of Physiology
Hypertension and Renal Center of Excellence
Tulane University Medical SchoolNew Orleans, LA
![Page 2: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/2.jpg)
Performance Objectives1. Define and calculate the renal fraction of the cardiac output and the factors that influence it.
2. Know the average values for renal blood flow (RBF) and glomerular filtration rate (GFR) in adult humans. Compare blood flow and oxygen consumption in kidneys to that of skeletal muscle.
3. Define and calculate the filtration fraction.
4. Identify the extrinsic and intrinsic factors that regulate renal blood flow and renal vascular resistance. Predict changes in RBF and GFR caused by increases in sympathetic nerve activity and increases in circulating epinephrine.
5. Identify the major sites of renal vascular resistance and describe the hydrostatic pressure profile along the renal vasculature.
6. Describe the roles of hydrostatic and colloid osmotic pressures in regulating glomerular filtration rate. Describe the filtration barriers in the glomerular membrane. How are proteins and macromolecules restricted from passing into the tubular fluid?
7. Given the glomerular and Bowman’s space hydrostatic and colloid osmotic pressures, be able to calculate the net filtration force for glomerular filtration. Define the glomerular filtration coefficient and explain its role in determining GFR.
8. Define the phenomenon of renal autoregulation and describe the roles of tubuloglomerular feedback mechanism and the myogenic mechanism.
9. Predict the changes in RBF and GFR caused by increased angiotensin II levels, increased prostaglandin E2 formation, increases in nitric oxide formation and increases in renal sympathetic nerve activity.
10. Describe the changes in tubular reabsorption associated with changes in hydrostatic and colloid osmotic pressure in the peritubular capillaries.
11. Review and be prepared to discuss questions on p. 46.
![Page 3: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/3.jpg)
Kidney disease is a national epidemic, affecting about 20 million Americans, or one out of every nine adults. There is a World Kidney Day every year. This year, it is on Mar. 8.
A National Surge in Kidney Disease
The Washington Post, August 23, 2005
![Page 4: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/4.jpg)
Kidney Disease in the United States:Living on the Kidney Belt
![Page 5: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/5.jpg)
Good cholesterol, bad cholesterol and blood sugar levels are familiar to most African Americans at risk, but kidney disease is off the radar screen, a new study reports.
The rate of kidney failure for African Americans is four times higher than among Caucasians and one reason for this is that they are not aware when they have earlier stages of kidney disease, at a time treatment could prevent the damage from progressing to the point when dialysis or kidney transplant is necessary. The problem appears to be specific for kidney disease, since most African Americans who had diabetes, hypertension, or high cholesterol knew so.
Kidney Disease in African Americans Goes Undetected Until the Latest Stages
![Page 6: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/6.jpg)
Outline of Presentation
1. Relationship of renal physiology and hemodynamics to previous sections on cardiovascular function and body fluid regulation
2. Issues of clinical relevance
3. Structural functional relationships and review anatomy and histology and overall anatomy
4. Pressure profiles along the nephrovascular unit and glomerular and peritubular capillary dynamics
5. Restriction of macromolecular permeability and role of charge and size selectivity
6. Intrinsic versus extrinsic mechanisms
7. Effects of sympathetic stimulation
![Page 7: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/7.jpg)
The kidney presents in the highest degree the phenomenon of sensibility, the power of reacting to various stimuli in a direction which is appropriate for the survival of the organism; a power of adaptation which almost gives one the idea that its component parts must be endowed with intelligence.
E. H. Starling
![Page 8: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/8.jpg)
Homer Smith
Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself.
![Page 9: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/9.jpg)
Salt and Water Homeostasis
IntakeSkin and
RespiratoryLosses
FecalLoss
UrinaryExcretion
Net Balance of Salt and Water
EXTRACELLULAR FLUID VOLUME
InterstitialFluid Volume
BloodVolume
CardiacOutput
ArterialPressure
RenalExcretion
of Saltand Water
PlasmaCompositional
Alterations
NervousSystem
HormoneSystems
+ - - -
![Page 10: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/10.jpg)
Nephrovascular Unit
From Boron and Boulpaep
![Page 11: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/11.jpg)
Magic of the Kidney
![Page 12: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/12.jpg)
Kidneys: Arteriolar Network
![Page 13: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/13.jpg)
Renal Fraction
Cardiac Output = 6 liters/min
Renal Blood Flow = 1.2 liters/min
Picture from: http://www.tuberose.com/Kidneys.html
![Page 14: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/14.jpg)
Renal Fraction
RBF
CO
1.2 L/MIN
6 L/MIN
= 0.2 or 20%
![Page 15: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/15.jpg)
Renal Blood Flow
By: Kidney Weight
Total Renal Blood Flow = 1200 ML/MIN
Weight of Both Kidneys = 300 Grams (70 kg person)
RBF = = 4 ML/MIN-GM1200300
![Page 16: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/16.jpg)
Oxygen Consumption (Per 100 ML Blood)
20 ML O2
18.6 ML O2
A-V Difference = AO2 – VO2
![Page 17: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/17.jpg)
Total Oxygen Consumption
Total RBF O2 Consumed100 ML Blood
X
1200 ML/MIN X 1.4 ML = 16.8 ML/MIN
![Page 18: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/18.jpg)
Total Oxygen Consumption
![Page 19: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/19.jpg)
I Mimura & M Nangaku. Nat Rev Nephrol 6:667-678, 2010
Arterial – Venous Oxygen Shunt Between Artery and Vein
AVOxygenShunt
![Page 20: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/20.jpg)
I Mimura & M Nangaku. Nat Rev Nephrol 6:667-678, 2010
Arterial – Venous Oxygen Shunt
![Page 21: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/21.jpg)
Distribution of Glomerular & Postglomerular Blood Flow
Postglomerular Flow% Total
Preglomerular Flow% Total
![Page 22: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/22.jpg)
Renal Vascular and Tubular Network
![Page 23: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/23.jpg)
Renal Microvasculature
![Page 24: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/24.jpg)
Glomerular Capillary
![Page 25: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/25.jpg)
Endothelial Fenestrations
![Page 26: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/26.jpg)
Glomerular Podocytes
![Page 27: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/27.jpg)
Glomerulus Between Afferent and Efferent Arterioles
![Page 28: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/28.jpg)
Blood Gel BM Bowman’sSpace
Jv
From: Ohlson et alAJP: Renal 280:F396, 2001
Glomerular Charge and Size Selectivity Preventing Leakage of Proteins into Tubules
![Page 29: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/29.jpg)
Effects of Charge on Glomerular Permeability
![Page 30: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/30.jpg)
Glomerular Membrane
P Garg and T Rabelink. ACKD 18:233‐242, 2011
![Page 31: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/31.jpg)
Passage of Macromolecules Across Glomerular Capillaries
![Page 32: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/32.jpg)
Hydrostatic Pressure Profile Along the Kidney
mmHg
Filtration: PG > πG
Reabsorption: PC < πCπif < πC
PRA
PG
PC
Arteries AfferentArteriole
EfferentArteriole
GlomerularCapillaries
PeritubularCapillaries Veins
100
80
60
40
20
RA RE
Navar, LG, 1998
![Page 33: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/33.jpg)
Hydrostatic Pressures
60 20
Net Hydrostatic Pressure= 40mmHg
![Page 34: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/34.jpg)
Colloid Osmotic Pressures
-31
Net Pressure= -31mmHg
037
25
![Page 35: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/35.jpg)
Effective Filtration Pressure
-31Hydrostatic Colloid
Osmotic Net
40
9
Effective filtration pressure = HP – COP = 40 – 31 = 9 mmHg
![Page 36: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/36.jpg)
Hydrostatic Pressure Profile Along the Kidney
RE = PG – PC/ RBF - GFR
Normal Human Values(Both kidneys)
RBF = 1200 ml/minRPF = 685 ml/minGFR = 130 ml/min
FF = GFR/RPF = 0.19
mmHg PRA
PG
PC
Arteries AfferentArteriole
EfferentArteriole
GlomerularCapillaries
PeritubularCapillaries Veins
RA = (100 – 54)/1200 RE = (54 – 18)/(1200 – 130)
100
80
60
40
20
RA = PRA – PG/ RBF
Filtration
Reabsorption
Navar, LG, 1998
![Page 37: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/37.jpg)
Glomerular and Peritubular Capillary Dynamics
![Page 38: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/38.jpg)
Possible Mechanisms Mediating Decreases in Filtered Load or Enhancement of Peritubular Reabsorption
Preglomerular Constriction
glomerular pressure
blood flow and GFR
peritubular and renal interstitial pressure
Preglomerular and Efferent Constriction
No change or increases in glomerular pressure
glomerular colloid osmotic pressure
Less % change in GFR than in RBF
peritubular and renal interstitial pressure
Decreases in Filtration Coefficient
in GFR
No change or slight glomerular pressure
Less change in RBF than GFR
![Page 39: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/39.jpg)
Afferent Arteriole and Renal Corpuscle
![Page 40: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/40.jpg)
Ca2+
Ca2+-Cal
Ca2+Phosphoinositides
cAMP
cAMP
PhosphorylatedMLCK
(inactive)
Calmodulin
Myosin LightChain Kinase
(MLCK)
MyosinLight Chain
(MLC)
Actin
DAG + IP3
PKC
VOC
PKA
S R
Ca2+
ROC
PLC Gs
Ad Cy
R+
-
Active MLCK
PhosphorylatedMLC
TensionDevelopment
Ca2+
Ca2+
Smooth Muscle Cell
![Page 41: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/41.jpg)
Endothelial Influences on Vascular Smooth Muscle
NOEDHF
PGI2
TXA2EDCF
PGF2
ET
Smooth Muscle Cell
Endothelial Cell
Ang II
Ang I
ACE
CGRP
Insulin
Histamine
VasopressinThrombin
SerotoninBradykinin
Acetylcholine
ATP/ADPTGF1
Leukotrienes
ShearStress
CalciumIonophore(A23187)
PlateletActivating
Factor
Substance P
![Page 42: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/42.jpg)
Outline of Presentation
8. Renal autoregulationa. Myogenic and tubuloglomerular b. Feedback mechanisms
9. Other intrinsic regulationsa. Endothelial factorsb. Renin-angiotensin system c. Prostaglandins
10. Presentation of clearance concepts and filtered loads11. Measurement of GFR12. Measurements of renal plasma flow and use of PAH
clearance13. Examples of clearance problems14. Assignment of Clearance Problems
![Page 43: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/43.jpg)
Arterial Pressure
Blood Composition
Neural Inputs
Hormonal Signalling
IntrarenalMechanisms
VenousEffluent
Urine
Lymph
Change in VolumeChange in CompositionRelease of Hormones
Waste ProductsExcess ElectrolytesFree Water Formation
Return Proteins to Circulation
Hormones
“Inputs and Outputs” of the Kidney
![Page 44: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/44.jpg)
Hydrostatic Pressure Predominates Filtration
Colloid Osmotic Pressure Predominates Reabsorption
Glomerular and Peritubular Systems
![Page 45: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/45.jpg)
The Tubular Transport Processes
![Page 46: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/46.jpg)
Control of Renal Blood Flow & Renal Vascular Resistance
Arterial Pressure
Renal Blood Flow
Renal Nerves
Hormones Plasma
Composition
Intrinsic Control Mechanisms (autoregulation, macula densa, paracrine factors)
Art. PRVR
Renal Vascular
Resistance
![Page 47: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/47.jpg)
Ca2+
Ca2+-Cal
Ca2+Phosphoinositides
cAMP
cAMP
PhosphorylatedMLCK
(inactive)
Calmodulin
Myosin LightChain Kinase
(MLCK)
MyosinLight Chain
(MLC)
Actin
DAG + IP3
PKC
VOC
PKA
S R
Ca2+
ROC
PLC Gs
Ad Cy
R+
-
Active MLCK
PhosphorylatedMLC
TensionDevelopment
Ca2+
Ca2+
Smooth Muscle Cell
![Page 48: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/48.jpg)
Endothelial Influences on Vascular Smooth Muscle
NOEDHF
PGI2
TXA2EDCF
PGF2
ET
Smooth Muscle Cell
Endothelial Cell
Ang II
Ang I
ACE
CGRP
Insulin
Histamine
VasopressinThrombin
SerotoninBradykinin
Acetylcholine
ATP/ADPTGF1
Leukotrienes
ShearStress
CalciumIonophore(A23187)
PlateletActivating
Factor
Substance P
![Page 49: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/49.jpg)
Hormones Affecting Renal Hemodynamics
1.Vasoconstricting Hormones:A. EpinephrineB. Angiotensin
2.Vasodilator Hormones:A. ProstaglandinsB. BradykininC. Atrial Natriuretic Peptide
![Page 50: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/50.jpg)
Increased Nerve Activity
![Page 51: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/51.jpg)
Effects of Renal Nerve Stimulation
Segm
ente
d Va
scul
ar
Res
ista
nce
% C
ontr
ol
Glo
mer
ular
Fi
ltrat
ion
Rat
ePl
asm
a Fl
ow%
Con
trol
Preglomerular
Efferent
Frequency of Renal Nerve Stimulation (Hz)
![Page 52: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/52.jpg)
Hemorrhage Induced Renal
Nerve Activation
![Page 53: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/53.jpg)
ANP Responses
![Page 54: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/54.jpg)
Renal Hemodynamics
INTRINSIC
EXTRINSIC
Control Mechanism:AutoregulationTubuloglomerular FeedbackParacrine Factors
Control Mechanism:Sympathetic NervesHormonesOther
![Page 55: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/55.jpg)
Renal Blood Flow Versus Pressure
RENAL ARTERIAL PRESSURE, mmHg
RE
NA
L B
LOO
D F
LOW
ml/m
in. g
0 50 150100 200
5
4
3
2
1
0
Normal Range
![Page 56: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/56.jpg)
Circadian Rhythms in Blood Pressure in Normal Subjects and Hypertensive Patients
Normotensive Patients(N=6)
Hypertensive Patients(N=20)
Blood Pressure(mmHg)
Blood Pressure(mmHg)
Time of Day (h) Time of Day (h)
![Page 57: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/57.jpg)
Renal Autoregulatory Responses to Changes in RAP
RA
RENAL ARTERIAL PRESSURE, mmHg RENAL ARTERIAL PRESSURE, mmHgR
EN
AL
BLO
OD
FLO
Wm
l/min
. g
VAS
CU
LAR
RE
SIS
TAN
CE
mm
Hg.
min
. g/m
l
20
15
10
5
00 50 150100 200 0 50 150100 200
5
43
2
1
0
RE
![Page 58: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/58.jpg)
Myogenic Responses
Po Pi
R
Tension(T)
T = (Pi - Po) R
Initial Tension IncreaseTension Decline Upon Constriction
Gain =
(Pc - P) . RcP . (R - Rc)
=
L n 8P R4
Flow =
![Page 59: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/59.jpg)
Renal Autoregulatory Responses to Changes in RAP
Renal Arterial Pressure (mmHg)
Ren
al B
lood
Flo
wm
l/min
/gVa
scul
ar R
esis
tanc
em
mH
g/m
in/g
/ml
Glo
mer
ular
Filt
ratio
nR
ate,
ml/m
in/g
Pres
sure
mm
Hg
![Page 60: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/60.jpg)
Proximal Tubule
Distal Tubule
Collection or Pressure Pipette
Wax Blocking Pipette
Perfusion Pipette
Micropuncture and Microperfusion
![Page 61: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/61.jpg)
Macula Densa – Vascular Pole
![Page 62: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/62.jpg)
Components of the Tubuloglomerular Feedback Mechanism
ArterialPressure Plasma Colloid
Osmotic Pressure
Proximal Tubuleand Loop of Henle
Reabsorption
Afferent ArteriolePreglomerularResistance
Macula Densa:a) Sensor Mechanismb) Transmitter
GlomerularPressure andPlasma Flow
GlomerularFiltration
Rate
Early Distal Tubule:Flow Related ChangesOsm and NaCl Conc.
GlomerulotubularBalance
Proximal toDistal Tubule
Flow
![Page 63: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/63.jpg)
Intact and Interrupted TGF
![Page 64: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/64.jpg)
Tubuloglomerular Feedback Mechanism
PerfusionPipette
CollectionPipette
WaxBlockingPipette
DistalTubule
MaculaDensa
ProximalTubule
Distal Nephron Delivery
Sing
le N
ephr
onG
FR
Ca++ Channel BlockerAng II BlockadeCytochrome P450 Blockade NO PGI2
Sensitivity:
Normal
Sensitivity: Ang IINOS Blockade Thromboxane HETE
![Page 65: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/65.jpg)
Autoregulation and TGF
HemodynamicInputs
TubularMetabolicFunction
![Page 66: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/66.jpg)
Renal Autoregulation
Physiological:
Pathological:
•Capability to maintain hemodynamic function in balance with metabolic capabilities of tubules.
maintain RBF and GFR in face of extrinsic perturbations
alter RBF and GFR in response to body fluid volume and functional demands
•Reserve vasodilatory capability following pathological insults.
glomerular pressure of all nephrons to compensate for Kf such as in acute renal failure and glomerulonephritis
hyperfiltration in remaining nephrons after loss of functional nephrons
![Page 67: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/67.jpg)
Receptor PLA2
Arachidonic Acid
COOH
EETS20-HETE
Epoxygenase
Hydroxylase
PGE2
Leukotrienes 12-HETE
PGI2TXA2
TXA2 SynthaseIsomerases
ProstacyclinSynthase
PGH2
HPETE
O
CH2-O-C-R
AA-CH
CH2-PO4-R'
Lipoxygenase
Cyclooxygenase
Cytochrome P450
RenalVasodilation Renal
Vasoconstriction
RenalVasoconstriction
RenalVasodilation
RenalVasoconstriction
RenalVasoconstriction
Renal Actions of Arachidonic Acid Metabolites
![Page 68: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/68.jpg)
Renal Hemodynamic Responses to NSAIDs in Sodium Repleted and Depleted Conditions
Na+ Replete
Na+ Deplete
Na+ Replete
Na+ Deplete
Control NSAID
Ren
al P
lasm
a Fl
owm
l/min
GFR
ml/m
in
![Page 69: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/69.jpg)
Renin Angiotensin System
NaClIntake
ArterialPressure
ECFVVolume
StressTrauma
Macula Densa Baroreceptors
Sympathetic Nervous System
ReninRelease
Juxtaglomerular Cells
Cytosolic Ca++
cAMP
Diuretics
LoopDiuretics
Angiotensinogen
ReninInhibitors
Angiotensin IAngiotensinConverting
Enzyme
ACEInhibitors
ReceptorBlockersAngiotensinases
Receptor Binding &Biological Actions
Metabolites
Angiotensin II
Renin
PGE2
![Page 70: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/70.jpg)
Juxtaglomerular Apparatus
![Page 71: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/71.jpg)
Effects of Angiotensin II
![Page 72: Renal Hemodyn Lec 1-HX](https://reader033.fdocuments.us/reader033/viewer/2022052603/55cf9334550346f57b9cb2cd/html5/thumbnails/72.jpg)
●Tubuloglomerular Feedback and Autoregulation:►alters filtered load to maintain balance with metabolically determined tubular reabsorptive processes►maintains GFR and RBF during fluctuations in arterial pressure
●Renin –Angiotensin System:►alters levels of hemodynamic function in accord with status of sodium balance►stimulates sodium reabsorption►increases sensitivity of TGF mechanism►reduces RBF and GFR
●Prostaglandins:►complex system with capability to activate vasoconstrictor and vasodilator systems►partially counteract actions of Ang II
●Neural and Adrenergic Systems:►integration with overall need to maintain sodium balance►responds immediately to emergency conditions
Renal Hemodynamic Control Mechanisms