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Control of Peripheral Blood Flow

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Control of Peripheral Blood Flow (Chapter 23)

 

Objectives:

 

  • Describe the normal distribution of cardiac output among organs.
  • Explain the role of the sympathetic and para-sympathetic systems in blood flow regulation.
  • Describe the role of circulating agents in the regulation of blood flow.
  • Explain local regulation of blood flow: metabolic regulation, autoregulation, and edothelium derived relaxing factor.

 

  • Normal Distribution of Cardiac Output Among Organs

 

    • Variability among Resting Tissues

Adults may have cardiac outputs of about 5.4 l/min at rest. With a body weight of 70 kg, this corresponds to an average blood flow of 7.7 ml/min per 100 g of tissue. However, blood flow varies greatly among tissues, as shown below.

(Reprinted from circulatory Physiology-the essentials 2nd ed., (1984) by J.J. Smith & J.P. Kampine, Figure9.1, pate 139, Lippincott, Williams & Wilkins.)

As shown in Figure 1, the blood flow to skeletal muscle amounts to 21% of total cardiac output, similar to the kidney (20%), and the hepatic-splanchnic circulation (25%). The brain receives 14 % of cardiac output, the heart, 4.5%, and the skin, 7.5%. However, these blood flows do not match the organ weights. The brain and kidney, for instance, receive disproportionately greater blood flows than predicted by their weights. The brain accounts for only 2% of body weight but receives 14% of cardiac output. The kidney accounts for 0.5% of body weight but receives 20% of cardiac output. The gastrointestinal tract, spleen, and liver (commonly referred to as the splanchnic bed) account for 2% of body weight, but receive 25% of cardiac output at rest. By contrast, skeletal muscle accounts for the greatest proportion of body mass (45%), but it receives only 21% of blood flow at rest.

 

It is also evident that tissues differ in their ability to extract O2 from the blood as it passes from arteries to veins through capillaries. On the average the difference in concentration of O2 between arteries and veins in a given tissue bed (a O2 – vO2 difference) is approximately 5 ml O2 / 100 ml of blood. Yet considerable variability exists. The skin, being a tissue with a low metabolic rate, extracts relatively little O2, while the heart extracts a large proportion of the O2 delivered to it.

 

    • Variability in High Metabolic States

In addition to the variability of blood flow among tissues at rest, tissues also vary greatly in their ability to increase blood flow in response to demand.

(Reprinted from Circulatory Physiology-the essentials 2nd ed., (1984) by J.J. Smith & J. P. Kampine, Figure 9.2, page 140, Lippincott, Williams & Wilkins.)

Figure 2 illustrates the blood flows to various tissues, both at rest and under maximum dilation. The kidney, as noted above, has a high rate of blood flow at rest but maximal dilation only increases its blood flow by 17%. The central nervous system has a relatively high flow rate at rest but with maximal dilation flow increases by a factor of 3. By contrast in the myocardium, liver, and gastro-intestinal tract, blood flow can be increased by 5 to 8 times. Remarkably, blood flow in skeletal muscle can be increased from 0.75 ml /min/ 100g of muscle at rest to 18.0 ml /min/ 100g with maximum dilation; an increase of 2,400%! Considering that skeletal muscle comprises 45% of body mass, this increase can cause huge changes in cardiac output. Salivary glands can also demonstrate large increases in blood flow, but because of their small size the demand on cardiac output is not important.

 

  • Mechanism of Blood Flow Distribution: The Reservoir and the Faucet

The mechanism that allows distribution of blood flow to match tissue need in the body is similar in many respects to that of a municipal water supply. In a community water is distributed through pipes to homes. The presence of a water tower and various controls keeps the supply network at a high and relatively constant pressure. When anyone opens the faucet at home water comes out at a relatively constant pressure. The number and extent to which faucets are opened control the rate of water flow. It is critical to that the reservoir is adequate and the pressure at a relatively high and constant pressure. It is also important that not everyone takes a shower at the same time or pressure in the system will fall.

 

In the body, the high-pressure reservoir function is served by the arterial system. Arterial blood pressure is generated by the heart’s pumping action. Arterial pressure is monitored and maintained by reflex control mechanisms to be discussed later. This lecture will focus on the “faucets” of the arterial systems, the arterioles and the mechanisms that control their diameter. These mechanisms include neural control of arterioles by the sympathetic nervous system and “local” control of arterioles.

 

Vascular or Arterial Tone - From Figures 1 and 2 it may be deduced that the arterioles of most, if not all, vascular beds are partially constricted at any given moment. This is referred to as vascular tone and may be caused by continuous sympathetic stimulation or myogenic contraction. The fact that all beds have vascular tone allows blood flow to each bed to be increased by dilating its arterioles.

 

  • Cardiovascular Role of the Sympathetic Nervous System

 

    • Heart - The sympathetic nervous system (SNS) innervates and stimulates both chronotropic and inotropic effects on the heart mediated by β-1 adrenergic receptors, increasing cardiac output under most conditions.

 

    • Large Arteries - The large arteries are innervated by the SNS, which have α-1 adrenergic receptors. Sympathetic stimulation of the arterial smooth muscle does not greatly reduce the radii of large arteries, but does produce stiffer (less compliant) arterial walls.

 

    • Veins - The veins are heavily innervated by the SNS, which also have α-1 receptors. SNS stimulation reduces venous compliance considerably. Since the veins are normally very compliant, they usually contain two-thirds of the blood in the body. SNS stimulation mobilizes blood pooled in the veins by increasing peripheral venous pressure. Venous return to the heart is, therefore, increased.

 

    • Arterioles - The arterioles are densely innervated by sympathetic neurons. SNS stimulation causes release of norepinephrine that binds to α-1 receptors, which, in turn, provokes contraction of the arterial smooth muscle and a constriction (narrowing) of the arteriole. The resulting increase in resistance to flow reduces blood flow through the capillary bed distal to that arteriole. It also reduces hydrostatic pressure in that capillary bed thereby favoring reabsorption of fluid into the capillary. If an adequate number of arterioles are constricted, total peripheral resistance may increase and lead to increased mean arterial pressure. The arterioles of skin, skeletal muscle, and gastro-intestinal tract are richly innervated by the SNS. This is the primary mechanism of action of the SNS on the peripheral cardiovascular system. It serves both to control arterial pressure (reservoir pressure) as well as controlling flow into the vascular beds (faucet opening).

 

    • Adrenal Medulla - The adrenal medulla is, in essence, equivalent to a peripheral ganglion of the adrenergic (sympathetic) nervous system. Generalized sympathetic stimulation causes release of both epinephrine (80%) and norepinephrine (20%) from the adrenal medulla. Circulating epinephrine stimulates cardiac β-1 receptors and provokes positive inotropic and chronotropic effects. In high enough doses it binds to α-1 receptors and mimics the effects of sympathetic stimulation. However, skeletal muscle arterioles also contain a second type of β-adrenergic receptor (β-2 receptors) that has a higher affinity for epinephrine than the co-existent α-1 receptors. Low doses of epinephrine preferentially bind to β-2 receptors and produce vasodilatation. At higher doses epinephrine binds α-1, β-1 and β-2 receptors. Depending on the dose, therefore, epinephrine can produce either dilation or constriction of the vascular bed.

(Reprinted from Principles of Physiology 3rd ed.,(2000) by R.M. Berne & M.N.Levy, page 247 with permission from Elsevier.)

 

    • Sympathetic Cholinergic Fibers - A very limited number of terminal sympathetic neurons release acetylcholine as a neurotransmitter instead of norepinephrine. The distribution of these fibers is limited to the arterioles of skeletal muscle and to sweat glands. Stimulation of sympathetic cholinergic fibers, release of ACh, and binding to muscarinic receptors on the arteriolar smooth muscle produces dilation of the arterioles, increasing blood flow to the muscle. Stimulation of sweat glands increases sweating. These fibers are activated only under special circumstances and have little effect on overall blood pressure control or control of flow to the muscle or other tissues.

 

  • Cardiovascular Role of the Parasympathetic Nervous System

 

    • The Heart - The effect of stimulation of parasympathetic nervous system (PNS i.e. vagus) slows the heart rate.

 

    • The Peripheral Vasculature - The PNS does not innervate arteries in muscle or skin, veins, or arterioles. Therefore, the PNS does not have a significant effect on blood pressure control or control of flow through tissues. (However, the sacral division of the PNS does supply blood vessels of the external genitalia and the cranial division innervates some blood vessels of the brain.)

 

  • Circulating Agents with Cardiovascular Activity

Some molecules with known effects on the vascular system are listed below.

 

    • Histamine - vasodilates and increases capillary permeability, may be involved in local response to minor trauma, e.g. redness and swelling with a scraped skin

 

    • Angiotensin II - very strong vascular smooth muscle constrictor

 

    • Vasopressin - (Antidiuretic Hormone) strong vasoconstrictor

 

  • Local Regulation of Blood Flow

Such phenomena as vascular autoregulation, active hyperemia, and reactive hyperemia involve changes in tissue blood flow that can be demonstrated in the absence of sympathetic input or humoral agents, leading to the conclusion that local factors are controlling tissue blood flow directly.

 

    • Metabolic regulation

Active increase in blood flow - With exercise, skeletal muscle blood flow increases. The magnitude of the increase tissue blood flow is commensurate with the O2 demand of the tissue.

 

Reactive Hyperemia - If blood flow to a tissue is occluded temporarily, then restored, the resulting blood flow will increase above normal temporarily before returning to normal. The magnitude of the hyperemia occurring parallels the extent of the blood flow deprivation during the occlusion.

 

The mechanism of active and reactive hyperemias is related to metabolic changes in the tissue. Tissue metabolism consumes O2 and fuels (e.g. fatty acids), produces CO2 and releases K+ and H+, lactic acid, adenosine etc. In the absence of adequate blood flow, these ions and metabolites accumulate. It can be shown that low O2 content (hypoxia), elevated CO2 (hypercarbia), K+ (hyperkalemia) , and H+ (acidosis), and adenosine, can produce vasodilation. Thus in the absence of adequate blood flow (either due to elevated metabolism or occluded blood flow) these metabolites accumulate resulting in vasodilation. When blood flow is restored, the vessels are dilate and flow is elevated until the metabolic changes have been washed out.

Blood flow to the brain and heart are both under strong metabolic control. Increases in cardiac work are closely paralleled by increases in coronary blood flow, even in the absence of any changes in arterial pressure.

 

    • Autoregulation of Blood Flow (Myogenic)

In general, flow through a tissue bed is a direct function of the pressure difference across the bed (Pa-Pv) and the resistance of the vascular bed. All other things being equal, the higher the driving pressure (arterial pressure) the greater the blood flow. In a rigid pipe the relationship should be linear. However, in some tissue beds (e.g. kidney) blood flow changes little in the face of large changes in arterial pressure. In fact kidney retains a nearly constant blood flow over a broad range of arterial pressures (90-180 mm Hg). Alteration in arterial pressure has a direct effect on the resistance of the renal arterioles, such that reducing arterial pressure also reduces vascular resistance thereby maintaining blood flow near constant. In contrast, an increase in arterial pressure in the renal increases renal vascular resistance.

The kidney’s blood flow greatly exceeds its metabolic need. Thus it is difficult to ascribe regulation of blood flow to a metabolic mechanism. Instead a myogenic mechanism operates; an increase in stretch of arterial smooth muscle, such as might be seen by increasing arterial pressure, has the effect of causing contraction of the smooth muscle. In other words, when stretched, the smooth muscle contracts, producing an increase in vascular resistance, thereby minimizing an increase in blood flow.

 

    • Endothelium -Derived Relaxing Factor (EDRF)

EDRF is a molecule (nitric oxide, NO) that is released by the arterial endothelium in response to elevation of the pressure gradient along the long axis of the vessel, i.e. increased “shear stress”. EDRF produces dilation locally in the smooth muscle adjacent to its point of synthesis. This mechanism has been postulated to explain some autoregulation-like changes in blood flow. However, since autoregulation can still occur in a blood vessel from which the endothelium has been removed, it is unlikely that EDRF can fully explain the autoregulation phenomenon.

    • Interaction of Local and Neural Factors on Blood Flow

The distribution of sympathetic input varies among tissues. The blood vessels of the skin and splanchnic bed are strongly innervated by the SNS. The blood flow of these tissues is under strong sympathetic regulation. By example, skin blood flow may be reduced to near zero by cold, thereby reducing heat loss to the environment. So strong is the sympathetically mediated temperature regulation mechanism that blood flow to the skin may be reduced until frostbite occurs.

 

By contrast the vascular flow of the brain and heart appear to be under near total control of metabolic regulation.

 

Skeletal muscle combines both mechanisms. At rest (not exercising) skeletal muscle arterioles are under strong sympathetic tone. With exercise, metabolic demand increases and blood flow increases by metabolic autoregulation, overriding the sympathetic input.

 

Kidney blood flow is controlled by myogenic autoregulation; blood flow is near constant between Pa of 90 and 180 mmHg.

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