Vascular Resistance Is Affected by Intrinsic and Extrinsic Control Mechanisms

As described in Chapter 22, the blood flow through any organ or tissue is determined by the perfusion pressure (arterial pressure minus venous pressure) and by the resistance of the blood vessels of the organ (and by no other factors), as follows:

Blood flow=Perfusion pressure%Vascular resistance

Normally, all the organs of the systemic circulation are exposed to the same perfusion pressure. Therefore, differences in blood flow to the various organs result from their different vascular resistances. The vascular resistance of an organ is determined mainly by the diameter of its arterioles. Thus, arteriolar vasodilation and vasoconstriction are the mechanisms that increase or decrease the blood flow in one organ relative to another organ.

In general, the factors that affect arteriolar resistance can be divided into intrinsic and extrinsic factors. Extrinsic control involves mechanisms that act from outside an organ or tissue, through nerves or hormones, to alter arteriolar resistance. Intrinsic control is exerted by local mechanisms within an organ or tissue. For example, as described in Chapter 23, histamine is released from mast cells of a tissue in response to injury or during an allergic reaction. Histamine acts locally on the arteriolar smooth muscle to relax it. Dilation of the arterioles decreases arteriolar resistance and therefore increases blood flow to the tissue. Histamine is an example of a paracrine: a substance released from one type of cell that acts on another cell type in the vicinity. Paracrine signaling molecules move by diffusion, which is why paracrine signaling is only effective over very short distances. A second example of intrinsic control is the arteriolar dilation and increased blood flow during exercise in skeletal muscle. This example illustrates the general phenomenon of metabolic control of blood flow: tissues tend to increase their blood flow whenever their metabolic rate increases.

Although the arterioles in all tissues are affected by both intrinsic and extrinsic mechanisms, intrinsic mechanisms predominate over extrinsic mechanisms in the control of arterioles in the brain, heart (i.e., coronary circulation), and working skeletal muscle. By contrast, extrinsic mechanisms predominate over intrinsic mechanisms in the control of blood flow to the kidneys, splanchnic organs, and resting skeletal muscle. Skin is an example of an organ in which both intrinsic and extrinsic control mechanisms have strong influences. In general, local (intrinsic) control dominates extrinsic control in the critical organs: those that must have sufficient blood flow to meet their metabolic needs on a second-by-second basis for an animal to survive. Extrinsic control dominates intrinsic control in organs that can withstand temporary reductions in blood flow (and metabolism) to make extra blood available for the critical organs.

Metabolic Control of Blood Flow Is a Local Mechanism That Matches the Blood Flow of a Tissue to Its Metabolic Rate

Metabolic control of blood flow is the most important local control mechanism. For example, metabolic control accounts for the huge increase in blood flow through a skeletal muscle as it goes from rest to maximal exercise. The functional significance of metabolic control of blood flow is that it matches the blood flow in a tissue to the metabolic rate of the tissue. An increase in tissue blood flow in response to increased metabolic rate is called active hyperemia (hyper means “elevated,” emia refers to blood, and active implies an increased metabolic rate).

Metabolic control of blood flow works by means of chemical changes within the tissue. When the metabolic rate of a tissue increases, its consumption of oxygen increases, and there is an increased rate of production of metabolic products, including carbon dioxide, adenosine, and lactic acid. Also, some potassium ions (K⁺) escape from rapidly metabolizing cells, and these ions accumulate in the interstitial fluid. Therefore, as the metabolism of a tissue increases, the interstitial concentration of oxygen decreases, and the interstitial concentrations of metabolic products and K⁺ increase. All these changes have the same effect on arteriolar smooth muscle: they relax it (Table 24-1). The arterioles dilate, vascular resistance decreases, and more blood flows through the tissue.

Low levels of oxygen and high concentrations of metabolic products and K⁺ also cause relaxation of the precapillary sphincters (in the tissues that have them), and this opens more of the capillaries in the tissue to blood flow. As explained in Chapter 23, the opening of more capillaries decreases the diffusion distance between fresh, oxygenated blood and the metabolizing cells of the tissue. Opening more capillaries also increases the total capillary surface area for diffusional exchange. The net result of the increased blood flow, the decreased diffusion distance, and the increased total capillary surface area is a more rapid delivery of oxygen and other metabolic substrates to the tissue cells and a more rapid removal of metabolic waste products from the tissue.

Metabolic control of blood flow involves negative feedback. The accumulation of metabolic products and the lack of oxygen initiate vasodilation, which increases blood flow. The increased blood flow removes the accumulating metabolic products and delivers additional oxygen. A new balance is reached when the increased blood flow closely matches the increased metabolic needs of the tissue. Figure 24-1 summarizes the major features of metabolic control of blood flow.

Reactive hyperemia is a temporary increase above normal in the flow of blood to a tissue after a period when blood flow was restricted. In this case the increased flow (hyperemia) is a response (reaction) to a period of inadequate blood flow. Mechanical compression of blood vessels is one cause of inadequate blood flow, and release of that mechanical compression elicits reactive hyperemia. This can be easily demonstrated in any accessible nonpigmented epithelial tissue. For example, press a finger against nonpigmented skin hard enough to occlude the blood flow. Maintain the pressure for about 1 minute, and then release. After release of the pressure, the previously compressed skin will appear darker (redder) for a short time, because blood flow will become greater than normal after the compression is released.

The same metabolic control mechanisms that account for active hyperemia also explain reactive hyperemia. During the period when mechanical compression restricts blood flow, metabolism continues in the compressed tissue; metabolic products accumulate, and the local concentration of oxygen decreases. These metabolic effects cause dilation of the arterioles and a decrease in arteriolar resistance. When the mechanical obstruction to flow is removed, blood flow increases above normal until the “oxygen debt” is repaid and the excess metabolic products have been removed from the compressed tissue. Figure 24-2 compares active and reactive hyperemia.

Autoregulation Is a Relative Constancy of Blood Flow in an Organ Despite Changes in Perfusion Pressure

Metabolic control mechanisms also participate in the phenomenon known as blood flow autoregulation. Autoregulation is evident in denervated organs and organs in which local control of blood flow is predominant over neural and humoral control (e.g., in coronary circulation, brain, and working skeletal muscle).

Figure 24-3 summarizes an experiment that demonstrates autoregulation in the brain. Initially, the perfusion pressure (arterial pressure minus venous pressure) in this animal is 100 mm Hg, and the blood flow to the brain is 100 milliliters per minute (mL/min) (point A). When perfusion pressure is increased suddenly to 140 mm Hg, brain blood flow rises initially to 140 mL/min but returns toward its initial level over the next 20 to 30 seconds. Eventually, blood flow reaches a stable level of about 110 mL/min (point B). Conversely, if the perfusion pressure is decreased suddenly from 100 to 60 mm Hg, blood flow in the brain decreases initially to 60 mL/min but returns toward its initial level over the next 20 to 30 seconds (see dashed lines in the top and middle graphs of Figure 24-3). Eventually, blood flow reaches a stable level of about 90 mL/min (point C). These stable responses are plotted in the bottom graph. The remainder of the bottom graph is obtained in a similar way; that is, perfusion pressure is set artificially to various levels, ranging from 40 to 220 mm Hg, and the resulting steady-state levels of blood flow are plotted.

Over a considerable range of perfusion pressure (about 60 to 190 mm Hg), relatively little change occurs in steady-state blood flow to the brain; that is, brain blood flow is autoregulated. The range of perfusion pressures over which flow remains relatively constant is called the autoregulatory range. Autoregulation fails at very high and very low perfusion pressures. Extremely high pressures result in marked increases in blood flow, and extremely low pressures result in marked decreases in blood flow. Nevertheless, over a considerable range of perfusion pressure, autoregulation keeps blood flow in the brain relatively constant.

Figure 24-4 shows how the metabolic control mechanisms previously described can account for the phenomenon of autoregulation. If the metabolic rate of an organ does not change but perfusion pressure is increased above normal, the increased pressure forces additional blood flow through the organ. The additional blood flow accelerates the removal of metabolic products from the interstitial fluid and increases the rate of oxygen delivery to the interstitial fluid. Therefore the concentration of vasodilating metabolic products in the interstitial fluid decreases, and the concentration of oxygen in the interstitial fluid increases. These changes cause the arterioles of the tissue to constrict, which increases the resistance to blood flow above normal. The consequence is that blood flow decreases back toward its initial level, despite the continuation of the elevated perfusion pressure.