Chapter 14 Organization and control of circulation to skeletal mucsle

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Chapter 14Organization and control of

circulation to skeletal mucsle


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


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


• 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

Organization and control of circulation to skeletal muscle

Arteriolar diameter: 10-100 μm


• 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

Resistance vessels


Resistance Vessels• Intimal surface

– Continuous layer of endothelial cells (50-100 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


Resistance vessels and their innervation


• 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 20-30 fibers

Capillaries: microvascular units


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


• 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

Muscle fiber-MVU relationships


O2 Diffusion: from microvessel to myocyte

• Capillary density– Principle determinant– Early thought

• Krogh cylinder– Each capillary supplies

fibers surrounding it• Theory arose from cross-

sectional (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


• According to Krogh model– Inc in metabolic rate

will reduce intracellular Po2

• Increases gradient (PcapO2-PiO2)

• At this point, Vo2 is limited by flow through capillary bed

• Best, to have many MVUs perfused at onset of contractions

Diffusion


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


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


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


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


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


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 supply-demand mismatches

– Also, helps explain why adjustment to higher exercise intensities is facilitated by prior warm-up exercise


• 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

Ascending Vasodilation


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


• 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

Myogenic autoregulation


• 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

Local metabolic vasodilation


Muscle pump• Rhythmic changes in

intramuscular pressure with dynamic exercise– Veins fill when muscle

relaxes– Blood is expelled when

muscle contracts– Valves maintain uni-

directional flow

Chapter 14 Organization and control of circulation to skeletal mucsle

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Transcript of Chapter 14 Organization and control of circulation to skeletal mucsle