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).
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).