The whole cardiovascular physiology caters to blood flow through the organs, and blood pressure is just one of the factors favouring tissue blood flow (perfusion).

1. Control of
Vascular tone
Tissue perfusion
Dr. Nyunt Wai
victor.nwai@gmail.com
2013
NW 1

2. Learning outcomes:
1. Define
(ssue
perfusion
and
state
its
significance
2. Define
vascular
tone,
and
state
the
func(ons
of
arteriolar
tone
3. Explain
the
roles
of
systemic
arterial
blood
pressure
and
arteriolar
tone
in
the
regula(on
of
(ssue
blood
flow:
4. Explain
the
effects
of
increased
arteriolar
tone
on
blood
flow
downstream
and
upstream
5. Define
blood
flow
rate
and
velocity
of
blood
flow
6. Recall
haemodynamics
from
the
perspec(ve
of
blood
flow:
• Explain
the
rela(onship
between
blood
flow
rate,
velocity
of
blood
flow
and
cross
sec(onal
area
of
a
vessel
or
vascular
bed
• Explain
turbulent
flow
and
the
factors
affec(ng
the
probability
for
turbulence
• On
the
basis
of
Poiseuille-­‐
Hagen
law,
explain
the
factors
affec(ng
(i)
blood
flow;
(ii)
resistance
to
blood
flow
• State
the
rela(onship
between
calibre
of
blood
vessel
(radius)
and
(i)
blood
flow;
(ii)
resistance
to
blood
flow
7. Describe
systemic
(neural
and
humoral)
and
local
control
of
vascular
tone
and
(ssue
blood
flow
(autoregula(on:
metabolic
and
myogenic
theories;
autoregulated
pressure-­‐flow
rela(on,
endothelial
hormones;
hyperaemia
and
reac(ve
hyperaemia)
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3. Outline
• What is tissue perfusion?
• Haemodynamic determinants of tissue
perfusion:
– The blood pressure and the blood flow - factors
– The resistance to blood flow – the vascular tone
– The velocity of blood flow
• Regulation of tissue blood flow:
– Systemic factors
– Local factors - Autoregulation
NW 3

4. O2, Nutrients
CO2, wastes
Capillary
Pressure at
the arterial
end
Pressure at
the venous
end
Tissue
Perfusion
Pressure
=
Pressure at
the arterial
end
Pressure at
the venous
end
-
Tissue A
Tissue
cells
Tissue Perfusion = Blood flow through the
tissue (capillary blood flow)NW 4

5. Blood flows from an area of high pressure to one of lower
pressure
NW 5

6. Central venous
pressure 4 mmHg
Systemic
arterial B.P.
100 mmHg
Tissue:
A
B
C
D
Systemic Circulation
LVRV
Arteriolar tone (continuous
partially contracted state of
arteriolar smooth muscle)
Ø regulates capillary blood
flow
Ø contributes to total
peripheral resistance
NW 6

7. Adequate
B.P.
Reduction of
arteriolar tone
To drive blood to the tissue
To allow more blood to
enter the capillaries in the
tissue
2 main factors
determining
tissue perfusion
NW 7

8. Blood flow rate (volume/time ;
cm3/s)
• directly proportional to the pressure
gradient
• There must be a sufficient pressure head
to drive the blood to all the tissues in the
body
NW 8

9. P1 = 100 mm Hg P2 = 60 mm Hg
P = Pressure gradient= 100 – 60 = 40 mmHg
The flow rate(cm3/s)
Haemodynamic
determinants of tissue
perfusion:
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10. No flow: Hydrostatic pressure exerted by the fluid remains the same
The pressure progressively falls – due to frictional resistance
The resistance is greatest in the arterioles
When the fluid is flowing…..
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11. Fluid flowing in concentric
layers or lamina:
Laminar or Streamline flow:
Frictional resistance between:
§ fluid and the wall
§ fluid layers
Velocity profile
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12. Flow Rate(cm3/s)
Cross-sectional area (cm2)
= cm/s
Flow Flow Flow
Cross-sectional area
NW 12

13. Flow
Layers mixed
up
Probabilty for
turbulence:
Reynold’s
number
Lack of slipperiness
between the fluid layers
Blood viscosity – mainly
determined by % of RBCs
Flow Flow
Creates
sounds
Silent
Why are systolic murmurs
common in anaemia?
> 2000
• Karotkoff sounds in
brachial artery in BP
measurement
• Bruits beyond
pathologically
narrowed artery
NW 13

14. Flow velocity =
flow rate
cross sectional area
Lowest in
capillaries:
More time
for
exchange
What if flow velocity is too slow?
Stagnant hypoxia
NW 14

15. Poiseuille- Hagen Law:
The 4th power Law
[The flow rate(cm3/s)]
NW 15

16. Radius (r ) decreases by
half (1/2)
The flow rate decreases
to 1/16th of the previous
value
NW 16

17. Radius increases 3 fold
Flow ∞ (radius) 4
The flow rate increases
è3x3x3x3 = 81 times
NW 17

18. Poiseuille- Hagen Law:
Ohm’s Law:
= ------------------
= ------------------
Small changes in radius (r)
(arteriolar tone) can cause very
large changes in
resistance (R)
NW 18

19. Vascular tone - definition
• Con(nuous
par(ally
contracted
state
of
the
vascular
smooth
muscle
cells
in
the
wall
of
the
vessels
• More
contrac(on
è
more
vascular
tone
è
more
vasoconstric(on
• Less
contrac(on
è
less
vascular
tone
è
less
vasoconstric(on
è
vasodila(on
NW 19

20. Vascular tone - types
• Arteriolar tone
• tone of precapillary sphincters
• Capillary tone?
– Nil (no vascular smooth muscle)
• Venous tone (much less than
arteriolar tone)
Tone of
Precapillary
resistance
vessels
NW 20

21. Vascular tone - effects
• Increased tone in a segment of blood vessel
• e.g. increased arteriolar tone
• è decreased radius of arteriole
• è greatly increased resistance to blood flow
• è greatly decreased blood flow across the arteriole
• è the effects on blood volume
– Increased upstream (in the artery)
– Decreased downstream(in the capillaries)
UpstreamDownstream
UpstreamDownstream
ArteryArterioleCapillary
NW 21

22. Central venous
pressure 4 mmHg
Systemic
arterial B.P.
100 mmHg
Organ:
A
B
C
D
Systemic Circulation:
arterioles
Systemic
Arterial System
Increased arteriolar tone
in all organs: è Effect on
systemic arterial BP?
Effect on tissue perfusion
in these organs?
Arteriolar tone decreases in organ A
but increases in all other organs è
Effect on systemic arterial BP?
Effect on tissue perfusion in: organ A?
organ B? organ C?
Begins here
Ends here
NW 22

23. Effects of incr. arteriolar tone
• When generalized, incr. TPR è incr.
systemic arterial BP
• When localized, may not have
appreciable effect on the systemic B.P.,
but there could be decr. blood flow to the
capillaries of that tissue
– Decreased capillary blood flow è decr.
capillary hydrostatic pressure (HP)è decr. ISF
formation
NW 23

24. Effects of incr. venous tone
• Generalized venoconstriction in systemic veins
• è Increased venous pressure
• è Increased venous return to the heart
• è Increased ventricular filling and EDV
• è Increased stretch of muscles in ventricular wall
• è Increased force of contraction (Starling’s law)
• è Increased stroke volume
• è Increased cardiac output
• è Increased BP
• Net effect: translocation of blood from venous
system to the arterial system
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25. Effects of decr. vascular tone
• Generalized venodilation in systemic veins
• è decreased venous return to the heart
• è decreased EDV
• è decreased force of contraction (Starling’s law)
• è decreased stroke volume & cardiac output
¡ Generalized systemic arteriolar dilation
¡ è decreased total peripheral resistance
BP
NW 25

26. Vascular tone:
Basal Myogenic tone
• Spontaneous
discharge of
pacemakers cells
• Spread of AP
• Contraction of
vascular smooth
muscle
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27. Regulation of vascular tone
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28. Regulation of vascular tone
Systemic:
- Neural
- Humoral
Local:
- Myogenic
- Humoral
Humoral = chemical substances (e.g. hormones, ions,
metabolites, dissolved gases, drugs) in blood or other
body fluids
NW 28

29. Systemic Control : Neural-1
• Continuous Sympathetic noradrenergic discharge
(Sympathetic tone) maintains vascular tone
• Most important control
• moment to moment variation in vascular tone is effected by
variation in sympathetic tone
ACh
NAdr  receptor
Vascular
muscle
contraction
Vasocontriction
Thoracolumbaroutflow
Sympathetic ganglion
NW 29

30. Systemic Control : Neural - 2
• Sympathetic cholinergic vasodilator system supplies
the vessels of the skeletal muscles
• Not important for normal control
• Sudden emotional shock è activation of this system è pooling
of blood in skeletal muscles of lower limbs è fainting
ACh
ACh Muscarinic receptor
Vascular
muscle
relaxation
Vasodilation
Sympathetic ganglion
Thoracolumbaroutflow
NW 30

31. Systemic Control : Neural - 3
• Parasympathetic nervous system
• Not important for systemic control of vascular tone
• Causes vasodilation in
– actively secreting glands
– erectile reproductive tissue
• Mediated by Nitric Oxide (NO) from endothelial cells
ACh
ACh Muscarinic receptor
Vascular
muscle
relaxation
Vasodilation
NO
parasympathetic
ganglion
Craniosacraloutflow
NW 31

32. Systemic Control : Humoral
Circulating
Vasoconstrictors
• Noradrenaline
• Angiotensin II
• Vasopressin
• Adrenaline (skin,
splanchnic)
• Dopamine
• Neuropeptide Y
• Calcium ions
Circulating Vasodilators
¡ Adrenaline (liver,
skeletal muscle)
¡ Dopamine (kidney)
¡ Atrial Natriuretic
peptide (ANP)
¡ VIP (Vasoactive
Intestinal Peptde)
¡ Kinins
¡ Substance P
NW 32

33. Local Control : Humoral
Vasoconstrictors
• Serotonin (5-HT)
(from platelets)
• Thromboxane A2
(from platelets)
• Endothelin (from
endothelial cells)
Vasodilators
¡ Nitric oxide (from
endothelial cells)
¡ Prostacyclin (from
endothelial cells)
¡ Histamine
¡ Vasodilator
metabolites
(VDMs) from
tissue metabolism
NW 33

34. Vasoconstrictor
• Endothelin
(peptide)
Vasodilators
• NO
(gas)
• Prostacyclin
(prostaglandin)
Endothelial control of vascular tone:
Endothelial cells secrete
Vasoactive substances:
NW 34

35. Nitric oxide production
• L-arginine
• NO synthase
– Constitutive NOS (cNOS)
– Inducible NOS (iNOS)
• Production of NO
• Diffuses into smooth
muscle cell
• Activation of guanylyl
cyclase (GC)
• Increased cGMP
• è decr. Ca2+ conc.
• èRelaxation of
vascular smooth muscle
The effect of inhibitors of
cGMP-dependent
phosphodiesterase *?
*Contraction
(-)
NW 35

36. Stimuli for Nitric oxide production
• Acetylcholine
• Bradykinin
• Histamine (via H1 receptors)
• VIP
• Substance P
Vasoconstrictors:
Noradrenaline
Angiotensin II
RcAMP
Certain infections è septicaemia è inflammatory mediators è iNOS è
massive production of NO è vasodilation refractory to vasoconstrictor drugs
è refractory shock
Contraction
(-)
NW 36

37. Vascular actions of NO
• Directly causes vasodilation
• Mediates the action of some
vasodilators
• Modulate the vasoconstrictor action
of noradrenaline and AGII
endothelium
Vascular smooth muscle
contraction
NO
(-) (+)
Net effect:
vasoconstriction since
the direct effect is greater
Far greater
vasoconstriction if
NO is deficientNW 37

38. Vascular actions of NO
• Modulates the vasoconstrictor action of
endothelin (ET-1)
• Anti-thrombotic effect - inhibits platelet adhesion
to the vascular endothelium
• Anti-inflammatory effect - inhibits leukocyte
adhesion to vascular endothelium
• Anti-proliferative effect - inhibits smooth muscle
hyperplasia
Effects of NO deficiency?
NW 38

39. NO deficiency
• Vasoconstriction
– coronary vasospasm
– elevated TPR (systemic vascular resistance) è hypertension
• Thrombosis due to platelet adhesion and aggregation
and to vascular endothelium
• Inflammation due to upregulation of leukocyte and
endothelial adhesion molecules
• Vascular hypertrophy and stenosis
NW 39

40. Local Control :
Autoregulation of blood flow
• = the capacity of tissues to regulate their own
blood flow
• Well developed in the
– Heart (myocardium)
– brain
– Kidneys
– Exercising skeletal muscles
• Theories of autoregulation:
– Myogenic theory
– Metabolic theory
NW 40

41. Myogenic theory
Autoregulation
• Due to intrinsic contractile response of vascular
smooth muscle to stretch
¡ Well developed in the Kidneys
NW 41

42. Myogenic theory
Autoregulation
Incr. B.P. è Incr. stretch of
muscles
¡ Blood flow is maintained relatively constant despite an
increase B.P. How?
è stretched muscles contract è
smaller radius è greater
resistance
NW 42

43. Zone of
autoregulation
(for Curve B)
No
autoregulation
A
B
NW 43

44. Metabolic theory of
Autoregulation
Decreased BP. and blood flow to a tissue cause
• Decreased arterial inflow è a fall in tissue P02
• Decreased venous outflow è accumulation of
products of metabolism:
– Incr. PCO2 è incr. [H+]
– Incr. heatè incr. ISF temperature
– Incr. lactic acid è incr. [H+]
– Incr. osmolality
– Release of K+ (due to hypoxia)
– Release of adenosine (since ATP synthesis is reduced)
• All these act on smooth muscles of precapillary
resistance vessels to relax è increased radius
è increased blood flow (back to normal)
VDMs:
Vasodilator
Metabolites
NW 44

45. • Whenever the blood flow is reduced (decr. Supply) or
• tissue metabolism is increased (incr. demand)
• accumulation of VDMs reduces the vascular tone, and
increases the vessel radius
• Small increase in radius greatly increases blood
flow
NW 45

46. Metabolic theory of
Autoregulation
Vasodilator
metabolites
cause
Hyperaemia
(increased
blood
flow
in
the
8ssues)
• Ac8ve
hyperaemia:
– VDMs
maintain
the
increased
blood
flow
during
increased
metabolic
ac(vity
of
the
(ssue
.e.g.
exercising
muscle
• Reac8ve
hyperaemia:
– Increase
in
blood
flow
in
a
(ssue
when
its
circula(on
is
reestablished
a?er
a
period
of
occlusion;
and
this
more
than
compensates
for
a
decrease
in
blood
flow
that
has
occurred
during
occlusion
NW 46

47. Flow
returns
to
normal
as
the
VDMs
are
washed
way
During activity
After tremoval of occlusion
MMS Sessions
Skeletal muscle
blood flow during
exercise?
Myocardial perfusion
after coronary artery
spasm?
NW 47

48. Summary: Functions of normal arteriolar
tone
1. Contributes to normal systemic arterial BP
by decreasing the outflow of blood from the systemic
arterial system è rise in blood volume è rise in BP
2. Regulates tissue perfusion (capillary blood flow)
By varying the arteriolar tone
3. Prevents undue loss of plasma into the interstitial
space
By dissipating of much of the arterial BP (due to high
resistance) è low capillary hydrostatic pressure è less
fluid driven out of the capillary into the interstitial space
NW 48