Local control of blood flow.
In addition to the central control
of blood pressure and cardiac output, tissues need to be able to regulate their
own blood flow to match their requirements. This is provided by autoregulation,
metabolic factors and autocoids (local hormones).
Autoregulation (Fig. 24a). Autoregulation is the ability to
maintain a constant flow in the face of variations in pressure between ∼50 and
170 mmHg. It is particularly important in the brain, kidney and heart.
Two mechanisms contribute to
autoregulation. The myogenic response involves arteriolar constriction
in response to stretching of the vessel wall, probably due to activation of smooth
muscle stretch-activated Ca2+ channels
and Ca2+ entry. A reduction in
pressure and stretch closes these channels, causing vasorelaxation. The second
mechanism is due to locally produced vasodilating factors. An increase in blood flow dilutes these
factors, causing vasoconstriction, whereas decreased blood flow allows accumulation, causing vasodilatation.
Metabolic factors (Fig. 24b). Many factors may contribute to metabolic hyperaemia (increased blood flow). The most important are K+,
CO2 and adenosine, and, in some tissues, hypoxia. K+ is
released from active tissues and in ischaemia; local concentrations can
increase to >10 mm. It causes relaxation, partly by stimulating the Na+
pump, thus both increasing Ca2+ removal by the Na+–Ca2+ exchanger and
hyperpolarizing the cell (Chapter 21). The vasodilatory effects of increased
CO2 (hypercapnia) and acidosis are mediated largely through
increased nitric oxide production (Chapter 21) and inhibition of smooth
muscle Ca2+ entry. Adenosine is a potent vasodilator released from
heart, skeletal muscle and brain during increased metabolism and hypoxia. It
is produced from adenosine monophosphate (AMP), a breakdown product of
adenosine triphosphate (ATP), and acts by stimulating the production of cyclic
AMP (cAMP) in smooth muscle (Chapter 21). Hypoxia may reduce ATP
sufficiently for KATP channels to activate, causing hyperpolarization.
Autocoids are mostly important in special circumstances;
two examples are given. In inflammation, mediators such as histamine
and bradykinin cause vasodilatation and increase the permeability of
exchange vessels, leading to swelling, but allowing access by leucocytes and
antibodies to damaged tissues. The activation of platelets during
clotting releases the vasoconstrictors serotonin and thromboxane A2,
so reducing blood loss (Chapter 9).
Special circulations
Skeletal muscle. This comprises ∼50% of the body weight
and, at rest, takes 15–20% of cardiac output; during exercise, this can rise to
>80%. Skeletal muscle provides a major contribution to the total
peripheral resistance, and sympathetic regulation of muscle blood
flow is important in the baroreceptor reflex. At rest, most capillaries
are not perfused, as their arterioles are constricted. Capillaries are recruited
during exercise by metabolic hyperaemia, caused by the release of K+
and CO2 from the muscle, and adenosine. This overrides sympathetic
vasoconstriction in working muscle; the latter reduces flow in non-working
muscle, conserving cardiac output. It should be noted that muscular
contraction compresses blood vessels and inhibits flow; in rhythmic (phasic)
activity, metabolic hyperaemia compensates by vastly increasing flow during the
relaxation phase. In isometric (static) contractions, reduced flow can
cause muscle fatigue.
Brain. The occlusion of blood flow to the brain
causes unconsciousness within minutes. The brain receives ∼15% of
cardiac output, and has a high capillary density. The endothelial cells of
these capillaries have very tight junctions, and contain membrane transporters
that control the movement of substances, such as ions, glucose and amino acids,
and tightly regulate the composition of the cerebrospinal fluid. This
arrangement is called the blood–brain barrier, and is continuous except
where substances need to be absorbed or released from the blood (e.g. pituitary
gland, choroid plexus). It can cause problems for the delivery of drugs to the
brain, particularly antibiotics. The autoreg- ulation of cerebral blood
flow is highly developed, maintaining a constant flow for blood pressures between 50 and 170 mmHg. CO2 and K+
are particularly important metabolic regulators in the brain, increases causing
a functional hyperaemia linking blood flow to activity. Hyperventilation
reduces blood Pco2, and can cause fainting due to cerebral vasoconstriction.
Coronary circulation. The heart has a high metabolic demand and a
dense capillary network. It can extract an unusually high proportion of oxygen
from the blood (∼70%). In exercise, the reduced diastolic
interval (Chapter 18) and increased
oxygen consumption demand a greatly
increased blood flow, which is achieved under the influence of adenosine,
K+ and hypoxia. The heart therefore controls its own blood flow
by a well-developed metabolic hyperaemia. This overrides vasoconstriction
mediated by sympathetic nerves (Chapters 7 and 21), and is assisted by
circulating adrenaline (epinephrine) which causes vasodilatation via
β2-adrenergic receptors.
Skin (Fig. 24c). The main function of the cutaneous
circulation is thermoregulation. Thoroughfare vessels (Chapter 23), formed
from coiled arteriovenous anastomoses (AVAs), directly link arterioles
and venules, allowing a high blood flow into the venous plexus and the
radiation of heat. AVAs are found mostly in the hands, feet and areas of the
face. Temperature is sensed by peripheral thermoreceptors and in the hypothalamus,
which coordinates the response. When temperature is low, sympathetic
stimulation causes the vasoconstriction of cutaneous vessels; this also
occurs following activation of the baroreceptor reflex by low blood
pressure (e.g. pale skin in haemorrhage and shock) (Chapter 22). Piloerection
(raising of skin hair, ‘goosebumps’) traps insulating air. Increased
temperatures reduce sympathetic adrenergic stimulation, causing
vasodilatation, whereas activation of sympathetic cholinergic fibres promotes
sweating and release of bradykinin, which also causes
vasodilatation. The net increase in blood flow may be 30-fold.
Pulmonary circulation. The pulmonary circulation is not controlled
by either autonomic nerves or metabolic products, and the most important
mechanism regulating flow is hypoxic pulmonary vasoconstriction, in
which small arteries constrict to hypoxia. This is unique to the lung;
hypoxia causes vasodilatation elsewhere (see above). Hypoxic pulmonary
vasoconstriction diverts blood away from poorly ventilated areas of the lung,
thus maintaining optimal ventilation–perfusion matching (Chapter 30);
conversely, global hypoxia due to lung disease or altitude detrimentally
increases the pulmonary artery pressure (pulmonary hypertension). The
pulmonary capillary pressure is normally low (∼7 mmHg), but fluid filtration still occurs because the interstitial
pressure is low (approximately –4 mmHg)
and the interstitial colloidal osmotic
pressure is high (18 mmHg) (Chapter 23).
