Circulation Through Special Regions (Brain Circulation) PDF

Circulation Through Special Regions Brain Circulation and CSF Learning Outcomes • Describe the special features of the circulation in the brain. • Describe the blood-brain barrier. • Explain the role of cerebrospinal fluid and the surrounding cells on blood flow. • Explain the Cushing reaction. ...

Circulation Through Special Regions Brain Circulation and CSF Learning Outcomes • Describe the special features of the circulation in the brain. • Describe the blood-brain barrier. • Explain the role of cerebrospinal fluid and the surrounding cells on blood flow. • Explain the Cushing reaction. • 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, 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. • Blood reaches the brain through four source arteries —the two internal carotid arteries and the two vertebral arteries. • 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 vascular smooth-muscle cells (VCMCs) 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. • 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. Capillaries • One of the most characteristic features of the brain vasculature is the blood-brain barrier, 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 do not affect 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, O2, and CO2 (or other gases) can readily diffuse across the cerebral capillaries. • Lipid-soluble free forms of steroid hormones can also penetrate the brain with ease whereas protein-bound forms and, in general, all proteins and polypeptides do not. • Glucose crosses more slowly via facilitated diffusion. • The blood-brain barrier protects the brain from abrupt changes in the composition of arterial blood. • The blood-brain barrier may become damaged in regions of the brain that are injured, infected, or occupied by tumors. • Such damage can help identify 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—the capillaries are fenestrated and have permeability characteristics similar to those of capillaries in the intestinal circulation. • These areas are (1) the posterior pituitary (neurohypophysis) and the adjacent ventral part of the median eminence of the hypothalamus, (2) the area postrema, (3) the organum vasculosum of the lamina terminalis (OVLT, supraoptic crest), and (4) the subfornical organ (SFO). All have fenestrated capillaries, and because of their permeability they are said to be “outside the blood-brain barrier Circumventricular organs. The neurohypophysis (NH), organum vasculosum of the lamina terminalis (OVLT, organum vasculosum of the lamina terminalis), subfornical organ (SFO), and area postrema (AP) are shown projected on a sagittal section of the human brain. SCO, subcommissural organ; PI, pineal. 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. • 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. Cerebral Blood Flow • 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 Changes in regional blood flow in the brain. The investigators used the washout of 133 Xe, measured with detectors placed over the side of the patient's head, as an index of regional blood flow in the dominant cerebral hemisphere. The turquoise “hot spots” represent regions where blood flow is >20% above mean blood flow for the entire brain. At rest, blood flow is greatest in the frontal and premotor regions. The patterns of blood flow change in characteristic ways with the seven other forms of cerebral activity shown. (Data from Ingvar DH: Functional landscapes of the dominant hemisphere. Brain Res 107:181–197, 1976.) 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 the 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. • 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 the local production and release of adenosine, a potent vasodilator. • A local increase in brain metabolism also lowers PO2 while raising PCO2 and lowering pH in the nearby BECF. • These changes trigger vasodilation and thus a compensatory increase in blood flow. How does brain blood flow respond to systemic changes in pH? • Lowering of arterial pH at a constant PCO2 has little effect on cerebral blood flow because arterial H+ cannot easily penetrate the bloodbrain barrier and therefore does not readily reach cerebral VSMCs. • On the other hand, lowering of arterial pH by an increase in PCO2 rapidly leads to a fall in the pH around VSMCs because CO2 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 PCO2 caused by inhalation of 7% CO2 can cause cerebral blood flow to double. • Conversely, the fall in arterial PCO2 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 PO2 - 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 the release of adenosine, K+, or NO into the BECF. Intracranial Pressure • In adults, the brain, spinal cord, and spinal fluid are encased, along with the cerebral vessels, in a rigid bony enclosure. The cranial cavity normally contains a brain weighing approximately 1400 g, 75 mL of blood, and 75 mL of spinal fluid. • Because brain tissue and spinal fluid are essentially incompressible, the volume of blood, spinal fluid, and brain in the cranium at any time must be relatively constant (Monro–Kellie doctrine). Autoregulation maintains a fairly constant cerebral blood flow across a broad range of perfusion pressures • The perfusion pressure to the brain is the difference between the systemic arterial pressure (mean pressure, ~95 mm Hg) and intracranial venous pressure, which is nearly equal to the intracranial pressure (<10 mm Hg). • A decrease in cerebral blood flow could thus result from a fall in arterial pressure or a rise in intracranial (or venous) pressure. However, the local control of cerebral blood flow maintains a nearly constant blood flow through perfusion pressures ranging from ~70 to 150 mm Hg. This constancy of blood flow— autoregulation —maintains a continuous supply of O2 and nutrients. • In people who have chronic hypertension there is hypertrophic remodeling of their cerebral blood vessels, as well as blood vessels in other organs and the autoregulatory curve is shifted to higher blood pressures. • This resetting of cerebral blood flow autoregulation partially protects the brain from the damaging effects of high blood pressure. but also makes the brain vulnerable to severe ischemia if blood pressure is reduced too rapidly below the range of autoregulation. If arterial pressure falls below the limits of autoregulation, cerebral blood flow becomes severely decreased. Autoregulation of cerebral blood flow during acute changes in mean arterial pressure in subjects with normotension (blue curve) and chronic hypertension (red curve). The dashed vertical lines indicate the approximate normal autoregulatory range. • Increases in intracranial pressure compress the brain vasculature and tend to reduce blood flow despite autoregulatory vasodilation. In such cases, the brain regulates its blood flow by inducing reflexive changes in systemic arterial pressure. • This principle is exemplified by the Cushing reaction, an increase in arterial pressure that occurs in response to an increase in intracranial pressure. • The Cushing reaction is a special type of CNS ischemic response that results from increased pressure of the cerebrospinal fluid around the brain in the cranial vault. • For example, when the cerebrospinal fluid pressure rises to equal the arterial pressure, it compresses the whole brain, as well as the arteries in the brain, and cuts off the blood supply to the brain. • This action initiates a CNS ischemic response that causes the arterial pressure to rise. • When the arterial pressure has risen to a level higher than the cerebrospinal fluid pressure, blood will flow once again into the vessels of the brain to relieve the brain ischemia. • Ordinarily, the blood pressure reaches a new equilibrium level slightly higher than the cerebrospinal fluid pressure, thus allowing blood to begin to flow through the brain again. • The Cushing reaction helps protect vital centers of the brain from loss of nutrition if the cerebrospinal fluid pressure ever rises high enough to compress the cerebral arteries. Cerebrospinal Fluid (CSF) • CSF fills the ventricles and subarachnoid space. • In humans, the volume of CSF is about 150 mL and the rate of CSF production is about 550 mL/d. • Thus the CSF turns over about 3.7 times a day. • In experiments on animals, it has been estimated that 50– 70% of the CSF is formed in the choroid plexuses and the remainder is formed around blood vessels and along ventricular walls. Presumably, the situation in humans is similar. • The composition of CSF is essentially the same as that of brain extracellular fluid (ECF), which in living humans makes up 15% of the brain volume. • In adults, free communication appears to take place between the brain interstitial fluid and CSF, although the diffusion distances from some parts of the brain to the CSF are appreciable. • Consequently, equilibration may take some time to occur, and local areas of the brain may have extracellular microenvironments that are transiently different from CSF. • The most critical role of CSF (and the meninges) is to protect the brain. The dura is attached firmly to the bone. • Normally, there is no “subdural space,” with the arachnoid being held to the dura by the surface tension of the thin layer of fluid between the two membranes. • The brain itself is supported within the arachnoid by the blood vessels and nerve roots and by the multiple fine fibrous arachnoid trabeculae. • The brain weighs about 1400 g in air, but in its “water bath” of CSF it has a net weight of only 50 g. The buoyancy of the brain in the CSF permits its relatively flimsy attachments to suspend it very effectively. When the head receives a blow, the arachnoid slides on the dura and the brain moves, but its motion is gently checked by the CSF cushion and by the arachnoid trabeculae. • The pain produced by spinal fluid deficiency illustrates the importance of CSF in supporting the brain. • Removal of CSF during lumbar puncture can cause a severe headache after the fluid is removed, because the brain hangs on the vessels and nerve roots, and traction on them stimulates pain fibers. The pain can be relieved by intrathecal injection of sterile isotonic saline.