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Chapter 14
Organization and control of
circulation to skeletal mucsle
© 2007 McGraw-Hill Higher Education. All rights reserved.
Introduction
• Blood flow in
microcirculation
• Degree to which
muscle blood flow
can increase
• Relationship
between metabolism,
blood flow and Vo2
• Coupling between
skeletal muscle and
vascular supply
• Role of SNS
© 2007 McGraw-Hill Higher Education. All rights reserved.
Organization and control of
circulation to skeletal muscle
• Conduit arteries:
– Large, act like pipes to
convey large amounts of
blood to areas in bulk
• Feed arteries:
– Muscular, act as
resistance vessels
– Constrict or dilate to
control blood flow into
microvascular networks
• Both are external to muscle
– Not directly responsive
to vasoactive stimuli
produced within muscle
fibers
© 2007 McGraw-Hill Higher Education. All rights reserved.
Organization and control of
circulation to skeletal muscle
• Primary arterioles:
– Within skeletal muscle
– Branch into 2cd and
3rd order arterioles
• Distribute blood
within muscle
– 4th order and terminal
arterioles
• Control perfusion
of capillaries
• Collecting venules
– Receive effluent blood
from capillary bed
• These empty into
progressively larger
venules
© 2007 McGraw-Hill Higher Education. All rights reserved.
Arteriolar diameter: 10-100 μm
Resistance vessels
• Arteriolar control of blood flow
– Smooth muscle contraction
• VC and VD
• Smooth muscle cells
encircle arterioles
• Capillaries do NOT have
smooth muscle
– Exchange vessels
– While diameter of
caps is smallest
(maybe 5 μm), there
are many of them
– Low resistance and
high total surface
area
• Venules
– Have smooth muscle
– Regulates
capacitance of these
vessels
© 2007 McGraw-Hill Higher Education. All rights reserved.
Resistance Vessels
• Intimal surface
– Continuous layer of
endothelial cells (50100 microns long and
5-10 microns wide)
• Direct contact with
blood
– Smooth muscle and
endothelium
• Separated by
elastic lamina
– Sympathetic nerves
• Surround feed
arteries and
arterioles
© 2007 McGraw-Hill Higher Education. All rights reserved.
Resistance vessels and their
innervation
© 2007 McGraw-Hill Higher Education. All rights reserved.
Capillaries: microvascular units
• Microvascular unit
– All the caps that arise
from a given terminal
arteriole
– TA’s run perpendicular
to fiber, to caps run
along fiber
– About 1 mm in length
– Maybe 20 caps arise
from each TA
– Cover about 0.1 mm3
– Each MVU supplies 2030 fibers
© 2007 McGraw-Hill Higher Education. All rights reserved.
Capillaries: muscle fiber and
MVU recruitment
• Perfusion is controlled at
the level of the TA
– Constriction: shuts off
MVU
– Dilation: opens MVU
• RBC distribution within
MVU
– Not uniform
– Determined in part by
metabolism of
contraction fibers and
hemodynamics
© 2007 McGraw-Hill Higher Education. All rights reserved.
Muscle fiber-MVU relationships
• Muscle fibers are several cm
long (order of magnitude longer
than MVU)
– Multiple MVUs supply each
fiber
– Muscle fibers of a motor unit
are dispersed within muscle
(not spatially organized)
– Thus, firing of a motor unit
will result in the perfusion of
more MVUs than needed
(particularly at low levels of
recruitment)
– Flow is both concurrent and
counter-current
• Offsets heterogeneities in
O2 delivery within and
between fibers
© 2007 McGraw-Hill Higher Education. All rights reserved.
O2 Diffusion: from microvessel to
myocyte
•
Capillary density
– Principle determinant
– Early thought
• Krogh cylinder
– Each capillary supplies
fibers surrounding it
• Theory arose from crosssectional (2D) analyses
– Thus, capillary density (# of
caps/mm2) or cap-to-fiber
ratio dominated early work
• Cap-to-fiber ratio can be
constant over training states;
how?
– 3D models are more insightful
• Cap volume per muscle fiber
volume
• Accounts for tortuosity and
branching not noted in 2D
modelling
© 2007 McGraw-Hill Higher Education. All rights reserved.
Diffusion
• According to Krogh
model
– Inc in metabolic rate
will reduce
intracellular Po2
• Increases
gradient (PcapO2PiO2)
• At this point, Vo2
is limited by flow
through capillary
bed
• Best, to have
many MVUs
perfused at onset
of contractions
© 2007 McGraw-Hill Higher Education. All rights reserved.
Red Blood Cell Transit Time:
determinant of extraction?
• Proportional to the length (TA to
CV) and inversely proportional to
velocity
• Transit time
– Increased length
• Determined by tortuosity,
number of caps perfused
and RBC spacing
– Velocity
• Determined by total
capillary volume density
• However
– Blood flow is NOT
homogeneous throughout
caps
– Caps are not straight tubes
• Difficult to determine transit time
© 2007 McGraw-Hill Higher Education. All rights reserved.
Altered capillary hematocrit
• Capillary hematocrit varies
greatly from rest to exercise
– Number of RBCs per unit
capillary length
– May double from rest to
exercise (20 to 40%)
– Reduces RBC spacing with
augments diffusion of O2
– Caused by glycocalyx
which retards plasma flow
to a greater degree at rest
© 2007 McGraw-Hill Higher Education. All rights reserved.
Oxygen diffuses out of arterioles
and between microvessels
• Major gradient is between cap
and myocyte
– Mean cap Po2 20-40 mmHg
– Intramyocyte Po2 <5 mmHg
• However, may be some cap to
cap O2 transfer, particularly
betw O2 depleted caps and
“fresher” caps
• May also be some arteriolar
and venular diffusion
– Likely small % of total
• All these diffusional relations
(cap-to-cap; arteriolar-venular)
– Likely reduce heterogeneity
of O2 delivery to muscle
© 2007 McGraw-Hill Higher Education. All rights reserved.
What determines O2 supply?
• Tissue demand clearly results in changing O2 supply
• Is there an O2 sensor?
– Tissue Po2 varies
• Myoglobin tends to smooth this out
• Likely that tissue Po2 determines metabolic state of cell
– Upstream sensor?
• Capillary Po2
• RBC
– Likely a combination
• Lowered tissue Po2 mandates increased non-aerobic
metabolism, which stimulates increased blood flow
(baroreceptors, NO-signalling)
• This serves to match supply to demand
© 2007 McGraw-Hill Higher Education. All rights reserved.
Blood flow controlled in response to
metabolic demand in muscle fibers
• Blood flow
– Proportional to
oxidative capacity
– Fiber type
• Type of activity
• Locomotor muscles
vs postural
–Diffs in NOS
© 2007 McGraw-Hill Higher Education. All rights reserved.
Meeting demand: Motor unit recruitment
promotes capillary perfusion
• Muscles fibers larger than
microvascular units which
supply them
• Muscle fibers of a particular
motor unit are dispersed
throughout muscle
– May seem wasteful, but
this feed forward type
mechanism may prevent
large scale supplydemand mismatches
– Also, helps explain why
adjustment to higher
exercise intensities is
facilitated by prior warmup exercise
© 2007 McGraw-Hill Higher Education. All rights reserved.
Ascending Vasodilation
•
At rest
– Resistance is high
• Blood flow is low
• O2 Extraction is relatively low
(~20%)
– Exercise
• First: increase extraction
(extraction reserve)
– Fall in intracellular Po2
– Increase in capillary
perfusion (dilation of
terminal arterioles)
• Vasodilations then spreads up the
vascular tree
– TA, distal arterioles, larger
arterioles, feed arteries
– These upstream events occur
in concert with greater motor
unit recruitment
© 2007 McGraw-Hill Higher Education. All rights reserved.
Functional hyperemia
• Multiple signals
– Vasoconstriction
• Inc in free Ca2+
• Voltage-modulated
Ca2+ channels
• Dependent upon K+
channels
• Also intracellular Ca2+
stores (ER)
– Second messenger
systems (IP3)
– Vasodilatory signals
• Hyperpolarization
• Nitric oxide
© 2007 McGraw-Hill Higher Education. All rights reserved.
Myogenic autoregulation
• Increase in wall stress
(proportional to transmural
pressure X luminal radius and
inversely proportional to wall
thickness)
– Stimulate smooth muscle
contraction
– Maintains constancy of
tissue blood flow
• During muscular contractions
• When muscle relaxes
– Reduces transmural
pressure and causes
vasodilation
© 2007 McGraw-Hill Higher Education. All rights reserved.
Local metabolic vasodilation
• Increase in metabolic rate causes
the release of vasodilatory
substances
– These help to match O2 supply
and demand
– Thus, while SNA and
autoregulation will tend to VC
areas that are inactive;
vasodilatory substances will do
the opposite
• Potassium
• EIHF (ex-induced
hyperpolarizing factor)
• NO (increased via shear
stress)
• Adenosine
– ALL increase with muscle activity
© 2007 McGraw-Hill Higher Education. All rights reserved.
Muscle pump
• Rhythmic changes in
intramuscular pressure
with dynamic exercise
– Veins fill when muscle
relaxes
– Blood is expelled when
muscle contracts
– Valves maintain unidirectional flow
© 2007 McGraw-Hill Higher Education. All rights reserved.