The skin is the largest organ of the body
The skin is the major barrier between the internal milieu of the body and the environment of the outside world. The skin is normally overperfused in relation to its nutritional requirements. Thus, local metabolic control of skin blood flow is of little functional importance. However, changes in blood flow to the skin also play a central role in the body's temperature regulation (see pp. 1200–1201).
In terms of blood flow, we can divide the skin into “apical” skin (Fig. 24-8A)—which is present on the nose, lips, ears, hands, and feet—and “nonapical” skin (see Fig. 24-8B). In skin, capillaries reach only as superficially as the dermis; the epidermis does not have a blood supply. The venules that are part of a plexus of vessels near the dermal-epidermal border (i.e., the most superficial vessels) may contain an appreciable volume of blood, thereby imparting a pinkish hue to individuals with light-colored skin. When cutaneous blood flow decreases, this volume of blood also decreases, lessening the reddish component of skin color (i.e., pallor). Local nutritional flow through the precapillary sphincters and capillaries is under the control of local vasodilator metabolites and sensory stimuli (e.g., temperature, touch, pain). For example, the vascular beds can respond to local thermal changes, largely independently of sympathetic nerve activity: the blood vessels dilate when the skin is directly heated and constrict when it is cooled.
FIGURE 24-8 Blood flow to the skin. A, In apical skin, glomus bodies (a-v anastomoses) can reach a density of ~500 per cm2 in the nail beds. B, The nonapical skin lacks glomus bodies. Postganglionic sympathetic fibers release norepinephrine (NE), causing the usual vasoconstriction. Preganglionic sympathetic fibers release acetylcholine (ACh) and cause vasodilation, perhaps mediated by formation of bradykinin.
The blood flow to the skin not only is affected by local metabolites and local warming and cooling but also is under sympathetic neural control. Increases in body core temperature increase blood flow to the skin, leading to a loss of heat. Decreases in core temperature result in the opposite effect of conserving heat. Unlike in other vascular beds, this neural control is far more important than local metabolic control in the overall regulation of skin blood flow.
Specialized arteriovenous anastomoses in apical skin help control heat loss
The apical skin at the extremities of the body has a very high surface-to-volume ratio that favors heat loss. Circulation to these apical regions has an unusual feature—arteriovenous (a-v) anastomoses called glomus bodies. (These glomus bodies are unrelated to the glomus cells of the peripheral chemoreceptors.) Glomus bodies of the skin are tiny nodules found in many parts of the body, including the ears, the pads of the fingers and toes, and the nail beds. As the afferent arteriole enters the connective tissue capsule of the glomus body, it becomes a vessel with a small lumen and a thick, muscular wall comprising multiple layers of myoepithelioid cells. These vessels—which have a rich sympathetic innervation—connect with short, thin-walled veins that eventually drain into larger skin veins. The a-v anastomoses, which are involved in heat exchange, are in parallel with the capillaries of the skin, which are involved in nutrient exchange (see Fig. 24-8A).
The anastomotic vessels are under neural control, rather than the control of local metabolites, and play a critical role in temperature regulation. In these apical regions, blood flow is under the control of sympathetic fibers that release norepinephrine and thereby constrict the arterioles, anastomotic vessels, and venules. Therefore, the increase in sympathetic tone that occurs in response to decreases in core temperature elicits vasoconstriction in the a-v anastomoses, a fall in blood flow, and a reduction in heat loss. Maximal sympathetic stimulation can completely obliterate the lumen of an anastomotic vessel, thus greatly reducing total blood flow to the skin. On the other hand, when the core temperature rises, the withdrawal of sympathetic tone leads to passive vasodilation; there is no active vasodilation. Indeed, blocking of the sympathetic input to a hand in a neutral thermal environment can increase blood flow 4-fold above basal levels—as much as heat stress can produce. Thus, sympathetic tone to the vasculature of apical skin is substantial at rest, particularly in cool environments, thereby minimizing heat loss.
The body uses a very different approach for regulating blood flow in nonapical skin. One important difference is that this vasculature almost completely lacks a-v anastomoses. A second important difference is that there are two types of sympathetic neurons innervating the vessels of the skin. Some release norepinephrine and some release acetylcholine.
Vasoconstriction occurs in response to the release of norepinephrine. In contrast to the situation in apical skin, blockade of sympathetic innervation to nonapical skin in a thermoneutral environment produces little change in skin blood flow, demonstrating that little vasoconstrictor activity is present at rest.
Vasodilation in nonapical skin occurs in response to sympathetic neurons that release acetylcholine (see p. 543). Indeed, blockade of sympathetic innervation to the nonapical skin in a warm environment produces vasoconstriction and a decrease in skin blood flow, demonstrating neurally directed vasodilation before the blockade. The precise mechanism of this vasodilation is obscure. One proposal is that the acetylcholine stimulates eccrine sweat glands, causing the secretion of sweat as well as enzymes that lead to the local formation of vasoactive molecules. For instance, sweat gland cells release kallikrein, a protease that converts kininogens to kinins, one of which is bradykinin (see p. 543). These kinins may act in a paracrine fashion on nearby blood vessels to relax VSMCs and thereby increase local perfusion. Cholinergic sympathetic neurons may cause vasodilation by means of a second pathway involving the co-release of vasodilatory neurotransmitters (e.g., calcitonin gene–related peptide, vasoactive intestinal peptide) that act directly on VSMCs, independently of sweat gland activity. Evidence for the second pathway is that the vasodilation cannot be blocked by atropine and is therefore independent from the actions of acetylcholine.
Mechanical stimuli elicit local vascular responses in the skin
If the skin is stroked mildly with a sharp instrument, a blanched line appears in the trailing path of the instrument. The immediate response is attributable to passive expulsion of the blood by the external mechanical force. During the next 15 to 60 seconds, the white reaction that ensues is caused by contraction of microvascular VSMCs and pericytes in response to mechanical stimulation. This active response has the effect of emptying the capillary loops, the collecting venules, and the subpapillary venous plexus of blood in a sharply delineated manner.
If a pointed instrument is drawn across the skin more forcefully, a series of reactions ensues that is collectively known as the triple response. Within several seconds, a band of increased redness appears due to a local dilation and increased perfusion of capillaries and venules within the perturbed area. This red reaction is independent of innervation and may persist for one to several minutes. The presumed cause is the local release of a vasodilator substance (e.g., histamine) from cells that were disturbed by the mechanical response.
If the stimulus is sufficiently strong or repeated, the reddening of the skin is no longer restricted to the line that was stroked but spreads to the surrounding region. This flare reaction appears several seconds after the localized redness and reflects the dilation of arterioles. The mechanism of the flare reaction is a local nervous response known as the axon reflex, N24-3 which depends on the branching of a single nerve fiber (see Fig. 15-29). A stimulus applied to one branch (containing the sensory receptor) gives rise to an action potential that travels centrally to the point of fiber branching. From this branch point, the afferent signal travels both orthodromically to the spinal cord and antidromically along the collateral branch. As a result, this collateral branch releases the vasodilating neurotransmitters. Sectioning of the nerve fiber central to the site of the collateral branch eliminates the awareness of the stimulus but does not eliminate the flare reaction until the nerve fiber degenerates.
When the stimulus is even more intense, as caused by the lash of a whip, the skin along the line of injury develops localized swelling known as a wheal. This local edema results from an increase in capillary permeability (e.g., in response to histamine) as filtration exceeds absorption. The wheal is preceded by and ultimately replaces the red reaction, appearing within a few minutes from the time of injury, and it is often surrounded by the flare reaction.