Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Special Circulations
In the preceding chapters, we considered blood flow to peripheral capillary beds as if the “periphery” were a single entity. In this chapter, we break that entity down into some of its component parts. Because each organ in the body has its own unique set of requirements, special circulations within each organ have evolved with their own particular features and regulatory mechanisms. Especially for times of great stress to the body, each organ possesses circulatory adaptations that allow it to make the changes appropriate for causing minimal harm to the overall organism. Here, we focus on the circulations of the brain, heart, skeletal muscle, abdominal viscera, and skin. Elsewhere we discuss other special circulations in the context of particular organs—the lungs (see pp. 683–689 ), the kidneys (see pp. 745–750 ), the placenta (see pp. 1136–1139 ), and the fetal circulation (see pp. 1157–1158 ).
The blood flow to individual organs must vary to meet the needs of the particular organ, as well as of the whole body
The blood flow to each tissue must meet the nutritional needs of that tissue's parenchymal cells, while at the same time allowing those cells to play their role in the homeostasis of the whole individual. The way in which the circulatory system distributes blood flow must be flexible so that changing demands can be met. In the process of meeting these demands, the body makes compromises. Consider the circulatory changes that accompany exercise. Blood flow to active skeletal muscle increases tremendously through both an increase in and a redistribution of cardiac output. Blood flow to the coronary circulation must also rise to meet the demands of exercise. Furthermore, in order to dispose of the heat generated during exercise, the vessels in the skin dilate, thereby promoting heat transfer to the environment. As cardiac output is increasingly directed to active muscle and skin, circulation to the splanchnic and renal circulations decreases, while blood flow to the brain is preserved.
This chapter focuses on the perfusion of select systemic vascular beds, but keep in mind that the lungs receive the entire cardiac output and therefore must also be able to accommodate any changes in total blood flow.
Neural, myogenic, metabolic, and endothelial mechanisms control regional blood flow
Several mechanisms govern vascular resistance and thus the distribution of blood circulating throughout the body. The interplay among neural, myogenic, metabolic, and endothelial mechanisms establishes a resting level of vasomotor tone. The extent to which a particular vascular bed depends on a particular blood-flow-control mechanism varies from organ to organ. We have discussed the following four mechanisms in the preceding chapters, and briefly review them here.
Neural Mechanisms
The resistance vessels of nearly every organ are invested with fibers of the autonomic nervous system (ANS), particularly those of the sympathetic division (see pp. 542–543 ). In addition to playing a critical role in controlling blood pressure and cardiac output, the ANS modulates local blood flow to meet the needs of particular tissues.
Myogenic Mechanisms
Many vessels, particularly the muscular arteries and arterioles that govern vascular resistance, are inherently responsive to changes in transmural pressure. Increased pressure and the accompanying stretch of vascular smooth-muscle cells (VSMCs) elicit vasoconstriction (see pp. 477–478 ), whereas decreased pressure elicits vasodilation. This myogenic response plays an important role in the autoregulation (see p. 481 ) that occurs in the vessels of the brain, heart, skeletal muscle, and kidneys.
Metabolic Mechanisms
Throughout the body, the vessels that govern blood flow are sensitive to the local metabolic needs of parenchymal cells. Table 20-9 lists several changes that act synergistically to increase local blood flow. For example, a decrease in 
or pH promotes relaxation of VSMCs, thereby causing vasodilation. In response to activity, excitable cells raise extracellular K + concentration ([K + ] o ), which also causes vasodilation. Tissues with high energy demands—such as the brain, heart, and skeletal muscle during exercise—rely heavily on such local control mechanisms.
Endothelial Mechanisms
Endothelial cells release a variety of vasoactive substances (see Table 20-10 ). For example, the shear stress exerted by the movement of blood through the vessel lumen stimulates the release of nitric oxide (NO), which relaxes VSMCs and prevents leukocyte adhesion. Endothelial cells and VSMCs also use gap junctions for electrical and chemical signaling between themselves, thereby coordinating their activity during blood flow control.
In addition to the previous mechanisms, which are part of a sophisticated feedback control system, other factors—which are not regulatory in nature—can affect the local circulation. These other factors are all mechanical forces that are external to the blood vessels and that tend to either to collapse or to open them. For example, in the heart (see p. 517 ) and skeletal muscle (see p. 517 ), muscle contraction transiently halts blood flow by compressing blood vessels within the tissue.
The Brain
Anastomoses at the circle of Willis and among the branches of distributing arteries protect the blood supply to the brain, which is ~15% of resting cardiac output
The brain accounts for only ~2% of the body's weight, yet it receives ~15% of the resting cardiac output. Of all the organs in the body, the brain is the least tolerant of ischemia. It depends entirely on oxidative sources of energy production. Each day, the human brain oxidizes ~100 g of glucose, 
N24-1 which is roughly equivalent to the amount stored as glycogen in the liver. Interruption of cerebral blood flow for just a few seconds causes unconsciousness. If ischemia persists for even a few minutes, irreversible cellular damage is likely.
N24-1
Brain Metabolism
As noted in Chapter 11 (see pp. 275 and 288 ), the brain has rather limited glycogen stores (~10% of the amount stored in the liver), and virtually all of these stores are in the astrocytes, which have mechanisms for transferring the energy to the neurons. As noted in the text on page 557 , the glucose consumption by the brain alone is capable of exhausting the liver's entire store of glycogen in only 1 day. When food is not eaten for >24 hours, the brain must either rely on glucose derived from gluconeogenesis (largely from the breakdown of muscle protein) or utilize an alternative fuel. For example, as levels of ketone bodies rise in the bloodstream during fasting, the enzymes required for their oxidation are induced in brain cells, thereby enabling an alternative substrate for energy production and conserving lean body mass.
The text addresses related issues in three locations: (1) on page 557 , (2) on page 287 (see Fig. 11-10 ), and (3) in Chapter 58 on metabolism.
Arteries
Blood reaches the brain through four source arteries —the two internal carotid arteries and the two vertebral arteries ( Fig. 24-1 ). The vertebral arteries join to form the basilar artery, which then splits to form the two posterior cerebral arteries, which in turn are part of the circle of Willis at the base of the brain. The internal carotid arteries are the major source of blood to the circle. Three bilateral pairs of distributing arteries (anterior, middle, and posterior cerebral arteries) arise from the circle of Willis to envelop the cerebral hemispheres. Smaller branches from the vertebral and basilar arteries distribute blood to the brainstem and cerebellum. The distributing arteries give rise to pial arteries that course over the surface of the brain, forming anastomoses, and then branch again into arterioles that penetrate the tissue at right angles to the brain surface. These penetrating arterioles branch centripetally to give rise to capillaries. The anastomoses on the cortical surface provide the collateral circulation that is so important should a distributing artery or one of its branches become occluded. Each of the four source arteries tends to supply the brain region closest to where the source artery joins the circle of Willis. If a stenosis develops in one source artery, other source arteries to the circle of Willis can provide alternative flow. Nevertheless, if flow through a carotid artery becomes severely restricted (e.g., with atherosclerotic plaque), ischemia may occur in the ipsilateral hemisphere, with impairment of function.
Veins
The veins of the brain are wide, thin-walled structures that are nearly devoid of VSMCs and have no valves. In general, the veins drain the brain radially, in a centrifugal direction. The intracerebral veins converge into a superficial pial plexus lying under the arteries. The plexus drains into collecting veins, which course over the distributing arteries and empty into the dural sinuses (see Fig. 11-1 B ). The exception to this radial pattern is the deep white matter of the cerebral hemispheres and basal ganglia; these regions drain centrally into veins that course along the walls of the lateral ventricles to form a deep venous system, which also empties into the dural sinuses. Nearly all of the venous blood from the brain leaves the cranium by way of the internal jugular vein. N24-2
N24-2
Emissary Veins
The emissary veins traverse the skull, carrying blood from the sinuses (e.g., superior sagittal sinus), which are surrounded by the dura mater inside the skull, to branches of the superficial temporal veins that are external to the skull. The emissary veins are typically responsible for little venous drainage from the brain.
Capillaries
One of the most characteristic features of the brain vasculature is the blood-brain barrier (see pp. 284–287 ), which prevents the solutes in the lumen of the capillaries from having direct access to the brain extracellular fluid (BECF). For this reason, many drugs that act on other organs or vascular beds have no effect on the brain. Polar and water-soluble compounds cross the blood-brain barrier slowly, and the ability of proteins to cross the barrier is extremely limited. Only water, O 2 , and CO 2 (or other gases) can readily diffuse across the cerebral capillaries. Glucose crosses more slowly via facilitated diffusion. No substance is entirely excluded from the brain; the critical variable is the rate of transfer. The blood-brain barrier protects the brain from abrupt changes in the composition of arterial blood. In a similar manner, a blood-testis barrier protects the germinal epithelia in males. The blood-brain barrier may become damaged in regions of the brain that are injured, infected, or occupied by tumors. Such damage can be helpful in identifying the location of tumors because tracers that are excluded from healthy central nervous system (CNS) tissue can enter the tumor. In specialized areas of the brain—the circumventricular organs (see pp. 284–285 )—the capillaries are fenestrated and have permeability characteristics similar to those of capillaries in the intestinal circulation.
Lymphatics
The brain lacks lymphatic vessels.
Vascular Volume
The skull encloses all of the cerebral vasculature, along with the brain and the cerebrospinal fluid compartments. Because the rigid cranium has a fixed total volume, vasodilation and an increase in vascular volume in one region of the brain must be met by reciprocal volume changes elsewhere within the cranium. Precise control of the cerebral blood volume is essential for preventing elevation of the intracranial pressure. With cerebral edema or hemorrhage, or with the growth of a brain tumor, neurological dysfunction can result from the restriction of blood flow due to vascular compression. An analogous situation can occur in the eyes of patients with glaucoma (see pp. 360–361 ). Pressure buildup within the eye compresses the optic nerve and retinal artery, and blindness can result from the damage caused by diminished blood flow to the retinal cells.
Neural, metabolic, and myogenic mechanisms control blood flow to the brain
Cerebral blood flow averages 50 mL/min for each 100 g of brain tissue and, because of autoregulation, is relatively constant. Nevertheless, regional changes in blood distribution occur in response to changing patterns of neuronal activity ( Fig. 24-2 ).
Neural Control
Sympathetic nerve fibers supplying the brain vasculature originate from postganglionic neurons in the superior cervical ganglia and travel with the internal carotid and vertebral arteries into the skull, branching with the arterial supply. The sympathetic nerve terminals release norepinephrine, which causes contraction of VSMCs. Parasympathetic innervation of the cerebral vessels arises from branches of the facial nerve; these nerve fibers elicit a modest vasodilation when activated. The cerebral vessels are also supplied with sensory nerves, whose cell bodies are located in the trigeminal ganglia and whose sensory processes contain substance P and calcitonin gene–related peptide, both of which are vasodilatory neurotransmitters. Local perturbations (e.g., changes in pressure or chemistry) may stimulate the sensory nerve endings to release these vasodilators, an example of an axon reflex (see p. 571 ). N24-3
N24-3
Axon Reflex
Axon reflexes are thought to occur when a nerve ending is depolarized by local factors (e.g., irritation, pressure, seizures, altered pH, high [K + ] o , or other chemical signals), triggering an action potential that travels anterograde along the axon to a branch point, where the action potential propagates back down another branch. Thus, an axon reflex is a local reflex arc that involves only the distal/peripheral part of a motor or sensory neuron.
In the case of a motor neuron, the stimulus would trigger an action potential that would move retrograde up the fiber to the branch point and then orthograde down to a terminal that would release its normal complement of neurotransmitters. Of course, when responding to its normal “central” stimuli, this motor neuron would function in the usual orthograde fashion.
In the case of a sensory fiber, the stimulus would travel orthograde along the axon to a branch point and then travel retrograde to other nerve endings. If these endings have release machinery, they could activate an effector. Varicosities on sensory fibers may contain substance P (SP) and calcitonin-gene–related peptide (CGRP), which the processes release in response to a local stimulus. Both SP and CGRP are vasodilatory neurotransmitters.
Another example of an afferent fiber that can release a neurotransmitter is the cranial nerve IX sensory neurons that innervate the glomus cells of the carotid body. As pointed out on pages 710–712 , this is an example of a bidirectional synapse. The glomus cells can trigger an action potential in the sensory neuron, and the sensory neuron can apparently release neurotransmitters that may modulate the glomus cell.
Axon reflexes can also occur in neurons of the CNS—for example, from one part of the cortex to another.
Despite this innervation, neural control of the cerebral vasculature is relatively weak. Instead, it is the local metabolic requirements of the brain cells that primarily govern vasomotor activity in the brain.
Metabolic Control
Neural activity leads to ATP breakdown and to the local production and release of adenosine, a potent vasodilator. A local increase in brain metabolism also lowers 
while raising 
and lowering pH in the nearby BECF. These changes trigger vasodilation and thus a compensatory increase in blood flow. Cerebral VSMCs relax mainly in response to low extra cellular pH; these cells are insensitive to increased 
per se, and decreased intracellular pH actually causes a weak vasoconstriction.
How does brain blood flow respond to systemic changes in pH? Lowering of arterial pH at a constant 
(metabolic acidosis; see p. 635 ) has little effect on cerebral blood flow because arterial H + cannot easily penetrate the blood-brain barrier and therefore does not readily reach cerebral VSMCs. On the other hand, lowering of arterial pH by an increase in 
(respiratory acidosis; see p. 633 ) rapidly leads to a fall in the pH around VSMCs because CO 2 readily crosses the blood-brain barrier. This fall in pH of the BECF evokes pronounced dilation of the cerebral vasculature, with an increase in blood flow that occurs within seconds. The rise in arterial 
caused by inhalation of 7% CO 2 can cause cerebral blood flow to double. Conversely, the fall in arterial 
caused by hyperventilation raises the pH of the BECF, producing cerebral vasoconstriction, decreased blood flow, and dizziness. Clinically, hyperventilation is used to lower cerebral blood flow in the emergency treatment of acute cerebral edema and glaucoma.
A fall in the blood and tissue 
—from hypoxemia or impaired cardiac output—may also contribute to cerebral vasodilation, although the effects are less dramatic than those produced by arterial hypercapnia. The vasodilatory effects of hypoxia may be direct or may be mediated by release of adenosine, K + , or NO into the BECF. N24-4
N24-4
Vasodilatory Effect of Hypoxia in the Brain
A fall in the blood and tissue 
—from hypoxemia or impaired blood flow to the brain—may also contribute to vasodilation in the brain, although the effects are less dramatic than those produced by arterial hypercapnia. Several mediators may underlie the effect of hypoxia:
- 1
Adenosine. Levels of adenosine increase with hypoxia, reflecting the breakdown of ATP. Virtually any condition that increases brain O 2 consumption will result in adenosine production and release within seconds. Because adenosine is a potent vasodilator (see Tables 20-8 and 20-9 ), increased adenosine levels tend to enhance blood flow and correct the hypoxia.
- 2
High [K + ]. Hypoxia, seizures, and electrical stimulation all elevate [K + ] in the BECF. Increased [K + ] o leads to vasodilation (see Table 20-9 ;
N24-6 ), which in turn tends to wash away the excess K + . Thus, elevated [K + ] o may be involved only in the early portion of a hyperemic response. - 3
NO. Both brain vascular endothelial cells and neurons contain nitric oxide synthase (see pp. 66–67 and 480 ) and thus can generate the highly permeable NO, which readily dilates the brain's resistance vessels.
- 4
Direct effects of low
. A mechanism receiving increasing attention is the effect of O 2 on the K + conductance of the VSMC membrane: a fall in 
increases K + conductance, promoting VSMC relaxation.
Myogenic Control
Cerebral resistance vessels are inherently responsive to changes in their transmural pressure. Increases in pressure lead to vasoconstriction, whereas decreases in pressure produce vasodilation.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here