Renal Blood Flow and Its Autoregulation (Seminar)

7/28/2019 Renal Blood Flow and Its Autoregulation (Seminar)

1/39

Renal Blood Flow and its

Autoregulation

Renal Blood Flow and itsAutoregulation

1


2/39

Overview

Features of Renal Blood Flow Anatomy

Special features

Autoregulation of Renal Blood Flow Site

Mechanisms

Dynamics and Efficiency

Techniques to study Renal Blood Flow

Applied Aspects

2


3/39

3

Renal Blood Flow

Delivery of oxygen and

nutrients to nephron

Concentration of Urine

Delivery of substances

for excretion in urine


4/39

Blood Flow in the Kidney

Blood flow under resting conditions : 20% of the

cardiac output

When the mass of kidneys is less than 1% of thebody weight!!

Flow rate : about 400 mL/100 g of tissue

than other well perfused organs

4Brenner & Rector, The Kidney, 9th

Ed., 2012


5/39

Blood Flow in Various Organs

Region Mass (kg) Flow(mL/min)

Flow/100g(mL/100g/min)

Liver 2.6 1500 57.7

Kidneys 0.3 1260 420.0

Brain 1.4 750 54.0

Skin 3.6 462 12.8

Skeletal

Muscle

31.0 840 2.7

Ganong, Review of Medical Physiology, 23rded., 2009 5

Resting Blood Flow in Various Organs in a 63-kg Adult Man


6/39

Peculiarities of Renal Blood Flow

Extraordinarily large amount of blood flow

Distribution of arteries - transmit pressure withminimum energy loss

High permeability of glomerular capillary bed Intra renal blood flow - heterogeneous

Low and high pressure capillary beds are arranged inseries

Blood flow determines oxygen demand

6

Brenner and Rector, The Kidney, 9th ed., 2012


7/39

Renal artery

Segmental artery

Lobar artery

Interlobar arteryArcuate artery

Interlobular artery

Afferent arteriole

Glomerulus

Efferent arteriole

Peritubular capillaries and Vasa Recta

Interlobular vein

Arcuate vein

Interlobar vein

Renal vein

7Guyton and Hall, Textbook of Medical Physiology, 12 th ed., 2011


8/39

8

Cortical Blood Flow Medullary Blood Flow

85-90% 10-15%

Cortex : filtration and

reabsorption

Medulla : urine concentration

Vasoconstrictors (Angiotensin II,

Endothelin, Norepinephrine)

have greater effect

Vasodilators (Prostaglandins,

Kinins, Nitric Oxide,

Acetylcholine) have greater

effect

High flow rates Lower flow rates



9/39

Total Renal Blood Flow : Calculation

First determine Renal Plasma Flow

Substance X -neither metabolized nor synthesized in the

kidneys - rate of its appearance in urine equals its rate of

extraction from blood

Rate of extraction from Blood

UxV = (Artx Venx) * RPF

RPF = UxV / (Artx Venx)

Since Plasma fraction = 1- HctRBF = RPF / (1 Hct)

Ux : urine conc. of X

V : volume of urine

Artx and Venx : arterial and venous concentrations of X

RPF : Renal Plasma flow

Hct : HematocritRBF : Renal Blood Flow9


10/39

Hydraulic Profile of Renal Circulation

10

RBF = P / R

Afferent and efferent

arterioles are major

sites of renal vascular

resistance



11/39

Vessel Pressure in

Beginning

Pressure at

End

% of Resistance

Renal Artery 100 100 ~0

Intelobar, Arcuate &

Interlobular Artery

~100 85 ~16

Afferent arteriole 85 60 ~26

Glomerular

capillaries

60 59 ~1

Efferent Arteriole 59 18 ~43

Peritubular

capillaries

18 8 ~10

Intelobar, Arcuate &Interlobular Veins

8 4 ~4

Renal vein 4 ~4 ~0

Guyton and Hall, Textbook of Medical Physiology, 12 th ed., 2011 11


12/39

12

A : Normal profile

B : Following Afferent arteriolar constriction

C : Following Efferent arteriolar constriction

Starling Forces

Constriction of Afferent arteriole

decreases GFR while that of efferent

arteriole increases GFR

But

Effect of afferent and efferent

arteriolar resistance change on RBF

are the same i.e. decreased blood flow

Best and Taylor, Physiological Basis of Medical Practice, 13th ed., 2012


13/39

Autoregulation of Renal Blood Flow

The ability to maintain a constant blood flow in

face of changes in perfusion pressure13


14/39

14

Decline in perfusion pressure?

Decline in Efferent arteriolar

resistance

Fall in GFR as wellas Glomerular

capillary pressure

But both GFR and RBF areautoregulated

So site of principal

resistance change is

PRE glomerular Brenner and Rector, The Kidney, 9th ed., 2012


15/39


16/39

16

When blood pressure is

increased in the blood vessels

and the blood vessels distend,

they react with a constriction

Sir William Maddock Bayliss

(1902)

Bayliss Effect


17/39

Myogenic response

Inherent property of the vascular smooth

muscletendency to contract when stretched

Response time in renal vessels (310 s)

Considerably faster than that in other vascular

beds

skeletal muscle,

brain and

skin

17


18/39

Renal tissue from newborn hamsters grafted into

cheek pouch of adult hamsters

Chamber perfused with Ringers Bicarbonate keeping

pH, pCO2 and pO2 constant

Syringe used to apply positive or negative pressure in

pulses of 10 mm Hg ; recorded using transducer

Blood vessel diameter measured using microscopy

18Gilmore et al., 1980, Circulation Research; 47 : 226- 230

Myogenic Mechanism


19/39

19

Perfusion reservoir(R),

Pressure reservoir(PR)

Chamber (C)

Microscope(M)

Formica plate(F)

Base plate of the chamber(BP)

Light rod(LR)Cheek pouch membrane (CPM)

Pressure transducer(PT)

Gilmore et al., 1980, Circulation Research; 47 : 226- 230


20/39

20

Afferent arteriole Efferent arteriole

Afferent arteriole showed increased arteriole diameter on application of

positive pressure and vice versa

Efferent arterioles showed a reverse response

Gilmore et al., 1980, Circulation Research; 47 : 226- 230


21/39

Preglomerular site of autoregulation

But responses were abolished bypapaverine

The findings are best

explained by a

Myogenic mechanism

21Gilmore et al., 1980, Circulation Research; 47 : 226- 230


22/39

22

Mechanosensitive

ion channelsIntegrin Activation

Phospholipase C

Activation

Depolarization ofcell membrane

Ca++ influx through

Voltage gated Ca++

channels

Contraction of

Vascular smooth

muscle

Phosphorylation of

Calmodulin and

Myosin light chain

kinase

Other mechanisms??

Cyt P450

PKC

Myosin Phosphorylase


23/39

Tubuloglomerular feedback

23

MD : Macula densaEGM : Extraglomerular mesangial cells

G : Granular cells

BM : Basement membrane;

BS : Bowman's space;

EN : Endothelial cell;

FP : Foot processesM : Mesangial cells

P : Podocyte

PE : Parietal epithelium;

PT : Proximal tubule cell

Berne and Levy, Physiology, 6th ed., 2010


24/39

Increased in delivery of

NaCl to the distal tubules

Sensed by Macula Densa

cells of JGA

Afferent arteriolarconstriction and decreased

GFR

24

??

Berne and Levy, Physiology, 6th ed., 2010


25/39

25

1. Uptake of Na+K+Cl+ by NKCC2

channel

2. Intra/Extra cellular production

of Adenosine

3. Activation of A1 receptors

causing increased Ca++ in extra

glomerular mesangial cells

4. Coupling between EMC,

granular cells and smooth

muscle cells

5. Vasoconstriction and inhibition

of Renin release



26/39

26

Bern and Levy, Physiology ,6th ed., 2012


27/39

3rd Mechanism

27Just A.Am J Physiol Regul Integr Comp Physiol 292:R1-R17, 2007.

Elimination of TGF on administration of Furosemide

Time (sec)


28/39

Underlying Mechanism

Not clear

Response resistant to inhibition of NOS, ACE

Inhibitors and changes in intra renal pressure

Cupples et alobserved disappearance of the

slow response on administration of AT2

receptor inhibitors

28


29/39

29

Dynamics of Response

Decreased

Perfusion Pressure

Myogenic Response


30/39

30

TGF shows initial Lag period of 15 s

Further delay occurs due to the time

needed for the molecular machineryto come into play

So total duration needed in 30 - 60 s


31/39

Relative contributions

Under resting conditions

Myogenic response 50%

Tubulo glomerular feedback 35 - 50%

3rd Mechanism - < 15%

31

Just A.Am J Physiol Regul Integr Comp Physiol 292:R1-R17, 2007.


32/39

32

Sympathetic Nerves

Nor epinephrine

Dehydration

Intense fear/Pain

Angiotensin II

Hemorrhage

PG I2, E1 and E2

NSAIDs

Increased Blood flow

Increased Shear force

Nitric Oxide


33/39

Techniques to study Renal

Microcirculation

Laser Doppler Flowmetery

Hydronephrotic Kidney

Isolated Renal Micro vessels

33


34/39

34

Laser Doppler Flowmetry Non invasive, continuous measurement of blood

flow on microscopic level

Recoding of frequency of oscillation produced bydoppler frequency shift of RBCs

Signal recorded as intensity oscillation

Analyzer calculates flux


35/39

35

Hydronephrotic Kidney

Steinhausen and colleagues

Germany (1983)

Non filtering kidney

Integrity of vessels preserved assuggested by histology and electrical

studies

Visualization of arteries during

perfusion

Dr Michael

Steinhausen


36/39

36

Isolated Renal Microvessels

R M Edwards (1983)

Renal microvessels isolated from rabbit kidney

Perfused to maintain constant intraluminal

pressure


37/39

Applied Aspects

Hemorrhage

Diabetes Mellitus

Raised NO, Hyperfiltration and glomerular damage

Hypertension

Raised NO

37


38/39

38

RENAL BLOOD FLOW

MYOGENIC MECHANISM

TUBULO GLOMERULAR

FEEDBACK

3RD MECHANISM

UNIQUE

NEURAL HUMORAL


39/39

39

Documents

Renal Blood Flow and Its Autoregulation (Seminar)