How does the body control blood flow to specific tissues?

Illustrate
your answer with reference to muscle blood flow.
The body must control blood flow through tissues due to variable metabolic demand, to ensure
adequate delivery of oxygen and metabolic substrates alongside removal of waste such as carbon
dioxide and lactic acid. This is achieved through predominantly through local control but central
control is also necessary in order to maintain a constant mean arterial pressure. Local control is
facilitated by myogenic or metabolic mechanisms, or through paracrine release of vasoactive
compounds from the capillary endothelium. This is in contrast to central control, which is neurogenic
or endocrine. In the specific case of muscle blood flow, the increased metabolic demands of
exercising muscle brings about a functional hyperaemia response which occurs in two broad stages.

Modulation of arteriolar resistance controls capillary blood flow

Blood flow is a function of pressure gradient and
resistance; figure 1 applies Darcy’s law (Q = P/R) to the
flow through a capillary bed perfused by a single
arteriole. The numerator here is the difference between
the arterial and venous pressure; the denominator sums
the resistances
Figure 1 of the arterioles, capillaries and venules.
Figure 1 can be simplified to figure 2 because 70% of the
resistance is arteriolar (and this is also the only directly
regulated resistance, through mechanisms that will be
discussed) and because the pressure gradient takes on a
small range of values (as rising arterial pressure causes
rising venous pressure and vice versa). Therefore, blood
Figure 2
flow is increased by reducing the arteriolar resistance.

Blood flow through capillaries is affected by the Fåhraeus-Lindqvist effect, which states that blood
flowing through a narrower tube (i.e. a capillary) will have a lower viscosity; the movement of
erythrocytes in the centre of the tube creates a plasma cell-free layer adjacent to the capillary wall,
which reduces resistance. This layer is very thin so the effect is only significant in capillaries of small
diameter, but helps to explain why tissue perfusion through capillaries can be maintained at a
relatively low blood pressure.

Overview of control of arteriolar smooth muscle

Local regulation increases bloodflow in response to reduced PO2, increased PCO2, decreased pH,
intracellular calcium and increased extracellular K+ during exercise. Arteriolar smooth muscle is
arranged circumferentially such that its contraction reduces the volume of the vessel lumen
(vasoconstriction); relaxation of the smooth muscle reduces vessel wall tension, so the force exerted
by the blood pressure increases the lumen volume (vasodilatation). Due to redundancies, control of
vascular tone is not fully understood.

Role of reduced PO2

The primary chemical cause of arteriolar vasodilation is the reduction of oxygen in the muscle
tissues. As muscle uses oxygen rapidly, the oxygen concentration in tissue fluids decreases, and as
arteriolar walls cannot maintain contraction in the absence of oxygen they vasodilate. Also, oxygen
deficiency causes release of vasodilator substances, particularly adenosine. Of note, experiments
have shown that adenosine cannot sustain vasodilation in skeletal muscle for more than two hours.

Role of the endothelium

The capillary endothelium’s role in regulating vascular
responses is shown by Furchgott’s experiments (figure 3),
which show that while noradrenaline (NE) increases tension
independently of an intact endothelium, acetylcholine (Ach)
can only dilate arteries with an intact endothelium. Ach and
a vasodilator peptide, bradykinin, stimulate nitric oxide
synthase to act on L-arginine in the endothelium to produce
the lipophilic gas NO, which stimulates a guanylyl cyclase in
vascular smooth muscle. This produces cGMP, which
activates a cGMP-dependent protein kinase to
phosphorylate myosin light chain kinase – inhibiting the
formation of cross-bridges to cause the muscle to relax.
Figure 3

Blood flow to muscle during exercise: functional hyperaemia

Strenuous exercise is one of the most stressful conditions faced by the normal circulatory system, as
there is such a large mass of skeletal muscle in the body and cardiac output must increase 4-5 times
even for a non-athlete. During exercise, blood flow to active muscles increases over 2 phases:
extremely quickly in phase 1, and more slowly in phase 2. During the fast phase, potassium ions are
the major local change; within 10 seconds, the interstitial concentration increases to 10mM. This is
due to the opening of voltage-gated potassium channels that open during repolarization, causes an
efflux of potassium down its electrochemical gradient out of cells. However, the rise in interstitial
[K+] has an unexpected effect because it hyperpolarizes arteriolar smooth muscle, which closes
voltage-gated calcium channels and relaxes the muscle. This is unexpected because it might be
expected that this increased interstitial [K+] would depolarise smooth muscle cells due to the
increase in equilibrium potential of potassium. The mechanism of hyperpolarisation is a combination
of enhanced Na+/K+-ATPase activity and enhanced activation of inwardly-rectifying K+ channels,
which contribute to maintenance of membrane resting potential. The resultant increased
intracellular potassium and increased potassium permeability causes hyperpolarisation.

A second fast cause of functional hyperaemia is the muscle pump. This is the acceleration of venous
return due to muscle contractions, which enhances cardiac output by increasing venous return but
also reduces local venous pressures, which increases the
pressure gradient between capillaries and venules.

During the maintained phase (phase 2) of functional

hyperaemia raised extracellular K+ continues to have a
central role, but a new mechanism is the activation of beta-
2 receptors on vascular smooth muscle by circulating
adrenaline. This increases cAMP levels in smooth muscle,
which activates PKA to open KATP channels. From this point
the route
Figure 4: to
thehyperpolarisation is the same mechanism as K+
two phases of functional
hyperaemia so both routes act synergistically.
accumulation,
During rest, many muscle capillaries have little or no bloodflow; the opening of dormant capillaries
diminishes the distance that nutrients must diffuse to reach the
contracting muscle fibres.

Figure 4 shows a simplified depiction of functional hyperaemia

to understand the concept of the two phases; however, as
shown in figure 5, there are actually fluctuations in blood flow
through a contracting muscle during rhythmic exercise, as
contraction closes the capillaries and severely restricts
bloodflow. During tetany, when the muscle is continually
contracted, there would be virtually no blood flow at all.

Figure 5

Systemic circulatory control in exercise

Systemic control, which must maintain a constant arterial blood pressure, reacts to the rapid drop in
total peripheral resistance produced by exercise (to as little as 20% of the resting value) by
increasing cardiac output. This is achieved by sympathetic venoconstriction; as the majority of blood
is in the veins, this reservoir will increase mean systemic filling pressure. Both a reduction in cardiac
vagal stimulation and an increase in cardiac sympathetic stimulation increase the heart rate, but the
latter also increases myocardial contractility; the net result of these influences is that mean ABP
actually rises slightly in exercise.

Another systemic effect is that of circulating adrenaline and noradrenaline released by the adrenal
medulla, which bind to alpha-1, beta-1 and beta-2 receptors, summarized in table 1. The receptors
have different effects, so their different distribution by location allows for adrenaline and
noradrenaline to control blood flow to specific organs. Although noradrenaline especially excites
alpha 1 receptors, which cause vasoconstriction, adrenaline has acts on beta 2 receptors which are
the more common receptors on the smooth muscle in arterioles, so there is overall vasodilation.

Table 1

Receptor Location Action

Alpha 1 Blood vessel walls Vasoconstriction
Beta 1 SA node, AV node, cardiac HR increased, automaticity,
myocytes contractility
Beta 2 Blood vessel walls Vasodilation

Conclusion
The control of blood flow to specific tissues is necessitated by their specialised roles; this essay has
discussed functional hyperaemia in muscle during exercise as an example. The overall mechanism is
complex and incompletely understood, partly due to the presence of redundancies. The increase in
blood flow results largely from local vasodilatory influences, which the systemic control mechanisms
then manage to prevent an accompanying reduction in total peripheral resistance, to keep mean
arterial pressure constant.