CHAPTER 61 Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism
Functioning of the brain is closely tied to the level of cerebral blood flow. Total cessation of blood flow to the brain causes unconsciousness within 5 to 10 seconds because of the decrease in oxygen delivery and the resultant cessation of metabolic activity.
Cerebral Blood Flow (p. 743)
The normal cerebral blood flow in an adult averages 50 to 65 mL/100 g, or about 750 to 900 mL/min; therefore the brain receives approximately 15% the total resting cardiac output.
Cerebral Blood Flow Is Related to the Level of Metabolism
Three metabolic factors—carbon dioxide, hydrogen ions, oxygen—have potent effects on cerebral blood flow. Carbon dioxide combines with water to form carbonic acid, which partially dissociates to form hydrogen ions. The hydrogen ions induce cerebral vasodilation in proportion to their concentration in the cerebral blood. Any substance that increases the acidity of the brain, and therefore the hydrogen ion concentration, increases cerebral blood flow; such substances include lactic acid, pyruvic acid, and other acidic compounds that are formed during the course of metabolism. A decrease in cerebral tissue Po2 causes an immediate increase in cerebral blood flow owing to local vasodilation of the cerebral blood vessels.
Measurements of local cerebral blood flow indicate that blood flow in individual segments of the brain changes within seconds in response to local neuronal activity. The act of making a fist with the hand causes an immediate increase in blood flow in the motor cortex of the opposite cerebral hemisphere. The act of reading increases blood flow in the occipital cortex and in the language perception area of the temporal cortex. Astrocytes (also called astroglial cells), specialized star-shaped nonneuronal cells that support and protect neurons, appear to help couple neuronal activity with local blood flow regulation by releasing vasoactive metabolites in response to stimulation of adjacent neurons.
Cerebral Blood Flow Autoregulation Protects the Brain from Changes in Arterial Pressure
Cerebral blood flow is nearly constant between the limits of 60 and 140 mm Hg mean arterial pressure. Arterial pressure therefore can fall to as low as 60 mm Hg or rise to as high as 140 mm Hg without significant changes occurring in cerebral blood flow. When the arterial pressure falls below 60 mm Hg, cerebral blood flow is usually compromised. If the arterial pressure rises above the limit of autoregulation, blood flow rises rapidly and overstretching or rupture of the cerebral blood vessels can result in brain edema or cerebral hemorrhage.
The Sympathetic Nervous System Has a Role in Regulation of Cerebral Blood Flow
The cerebral circulation has dense sympathetic innervation; under certain conditions, sympathetic stimulation can cause marked constriction of the cerebral arteries. During strenuous exercise or states of enhanced circulatory activity, sympathetic impulses can constrict the large and intermediate-sized arteries and prevent the high pressure from reaching small blood vessels. This mechanism is important for preventing vascular hemorrhage. Under many conditions in which the sympathetic nervous system is moderately activated, however, cerebral blood flow is maintained relatively constant by autoregulatory mechanisms.
Cerebral Microcirculation
The density of capillaries is four times greater in the gray matter of the brain than that in the white matter. The level of blood flow to the gray matter is therefore four times as great as that to the white matter, matching the much higher metabolic needs of gray matter. The brain capillaries are much less “leaky” than capillaries in other portions of the body. Capillaries in the brain are surrounded by “glial feet,” which provide physical support to prevent overstretching of the capillaries in the event of exposure to high pressure.
Cerebral “Stroke” Occurs when Cerebral Blood Vessels Are Blocked or Ruptured
Most strokes are caused by arteriosclerotic plaques that occur in one or more of the large arteries of the brain. Plaque material can trigger the clot mechanism, which may result in clot formation, artery blockage, and subsequent loss of function in the brain areas supplied by the vessel. In about one fourth of persons who develop strokes, the cerebral blood vessels rupture as a result of high blood pressure. The resulting hemorrhage compresses the brain tissue, leading to local ischemia and edema.
The neurological effects of a stroke are determined by which brain area is affected. If the middle cerebral artery in the dominant hemisphere is involved, the person is likely to become almost totally debilitated owing to loss of Wernicke’s area, which is involved in speech comprehension. In addition, these individuals often become unable to speak because of damage to Broca’s motor area for word formation, and loss of other motor control areas of the dominant hemisphere can create spastic paralysis of the muscles of the opposite side of the body.
Cerebrospinal Fluid (CSF) System (p. 746)
The entire cavity enclosing the brain and spinal cord has a volume of approximately 1650 mL; about 150 mL of this volume is occupied by CSF, and the remainder is occupied by the brain and spinal cord. This fluid, as shown in Figure 61–1, is found in the ventricles of the brain, the cisterns around the brain, and the subarachnoid space around both the brain and the spinal cord. These chambers are interconnected, and the pressure of the CSF is regulated at a constant level.
Figure 61–1 Arrows show the pathway of cerebrospinal fluid flow from the choroid plexuses in the lateral ventricles to the arachnoidal villi protruding into the dural sinuses.
Formation and Absorption of CSF
About 500 mL of CSF is formed each day. Most of this fluid originates from the choroid plexuses of the four ventricles. Additional amounts of fluid are secreted by the ependymal surfaces of the ventricles and the arachnoidal membranes. The choroid plexus is a cauliflower-like growth of blood vessels covered by a thin layer of epithelial cells. This structure projects into the temporal horn of each lateral ventricle, the posterior portion of the third ventricle, and the roof of the fourth ventricle.
The CSF is absorbed by multiple arachnoidal villi that project into the large sagittal venous sinus as well as into other venous sinuses of the cerebrum. The CSF empties into the venous blood through the surfaces of these villi.
The Perivascular Space Functions as a Lymphatic System for the Brain
As the blood vessels that supply the brain penetrate inward, they carry with them a layer of pia matter. The pia is only loosely adherent to the vessels, and this creates a space between the pia and the vessels called the perivascular space. The perivascular space follows both the arteries and veins into the brain as far as the arterioles and venules but not to the level of the capillaries.
Protein that leaks into the interstitial spaces of the brain flows through the perivascular spaces into the subarachnoid space. On reaching the subarachnoid space, the protein flows with the CSF and is absorbed through the arachnoidal villi into the cerebral veins.
CSF Pressure
CSF is formed at a nearly constant rate; therefore, the rate of absorption of this fluid by the arachnoidal villi determines both the quantity of fluid present in the ventricular system and the level of CSF pressure.
The arachnoidal villi function like one-way valves that allow CSF to flow into the blood of the venous sinuses but prevent the flow of blood into the CSF. Normally, the valvelike action of the villi allows CSF to flow into the venous sinuses when the pressure in the fluid is approximately 1.5 mm Hg greater than the pressure of the blood in the venous sinuses. When the villi become blocked by large particulate matter or fibrosis, CSF pressure can rise dramatically.
The normal CSF pressure is 10 mm Hg. Brain tumors, hemorrhage, or infective processes can disrupt the absorptive capacity of the arachnoidal villi and cause CSF pressure to increase to levels three to four times normal.
Obstruction to the Flow of CSF Causes Hydrocephalus
This condition is often defined as communicating hydrocephalus or noncommunicating hydrocephalus. With communicating hydrocephalus fluid flows readily from the ventricular system into the subarachnoid space, whereas with noncommunicating hydrocephalus the flow of fluid out of one or more of the ventricles is blocked.
The communicating type of hydrocephalus is usually caused by blockage of fluid flow into the subarachnoid space around the basal regions of the brain or blockage of the arachnoidal villi themselves. The noncommunicating type of hydrocephalus is usually caused by blockade of the aqueduct of Sylvius as a result of a congenital defect or brain tumor. The continual formation of CSF by the choroid plexuses in the two lateral ventricles and the third ventricle causes the volume of these ventricles to increase greatly. This flattens the brain into a thin shell against the skull. In neonates, the increased pressure also causes the entire head to swell because the skull bones have not yet fused.
Blood-CSF and Blood-Brain Barriers (p. 748)
The constituents of the CSF are not exactly the same as those of the extracellular fluid elsewhere in the body. Furthermore, many large molecular substances do not pass from the blood into the CSF or into the interstitial fluids of the brain. Barriers called the blood-CSF barrier and the blood-brain barrier exist between the blood and the CSF and brain fluid. These barriers are highly permeable to water, carbon dioxide, oxygen, most lipid-soluble substances such as alcohol, and most anesthetics; they are slightly permeable to electrolytes such as sodium, chloride, and potassium; and they are almost totally impermeable to plasma proteins and most non–lipid-soluble large organic molecules.
The cause of the low permeability of these barriers is the manner in which the endothelial cells of the capillaries are joined to one another. The membranes of the adjacent endothelial cells are tightly fused with one another rather than having extensive slit pores between them, as is the case with most other capillaries of the body. These barriers often make it impossible to achieve effective concentrations of therapeutic drugs, such as protein antibodies and non–lipid-soluble compounds in the CSF or parenchyma of the brain.
In some areas of the hypothalamus, pineal gland, and area postrema, substances diffuse with greater ease into the tissue spaces. The ease of diffusion in these areas is important because they have sensory receptors that respond to specific changes in the body fluids, such as changes in osmolality and in glucose concentration, as well as receptors for peptide hormones that regulate thirst, such as angiotensin II.
Brain Edema (p. 749)
One of the most serious complications of abnormal cerebral hemodynamics and fluid dynamics is the development of brain edema. Because the brain is encased in a solid vault, accumulation of edema fluid compresses the blood vessels, resulting in decreased blood flow and destruction of brain tissue. Brain edema can be caused by greatly increased capillary pressure or by a concussion in which the brain’s tissues and capillaries are traumatized and capillary fluid leaks into this tissue.
Once brain edema begins, it sometimes initiates a vicious circle. The edema fluid compresses the vasculature, which in turn decreases the blood flow and causes brain ischemia. The ischemia causes arteriolar dilation with further increases in capillary pressure. The higher capillary pressure causes more edema fluid, and the edema becomes progressively worse. The reduced blood flow also decreases oxygen delivery, which increases the permeability of the capillaries, allowing more fluid leakage. Decreased oxygen delivery depresses brain metabolism, which turns off the sodium pumps of the brain cells, causing them to swell.
Once this process has begun, heroic measures must be taken to prevent total destruction of the brain. One measure is to administer an intravenous infusion of a concentrated osmotic substance such as mannitol. This pulls fluid from the brain tissue through osmosis and breaks the vicious circle. Another procedure is to remove fluid quickly from the lateral ventricles of the brain through ventricular puncture, thereby relieving intracerebral pressure.
Brain Metabolism (p. 749)
Under resting conditions, the metabolism of the brain accounts for 15% of the total metabolism of the body even though the mass of the brain is only 2% of the total body mass. Under resting conditions therefore brain metabolism is about 7.5 times the average metabolism of the rest of the body.
The Brain Has Limited Anaerobic Capability
Most tissues of the body can go without oxygen for several minutes. During this time, the cells obtain their energy through anaerobic metabolism. Because of the high metabolic rate of the brain, anaerobic breakdown of glycogen cannot supply the energy needed to sustain neuronal activity. Most neuronal activity therefore depends on the second-by-second delivery of glucose and oxygen from the blood.
Under Normal Conditions, Most Brain Energy Is Supplied by Glucose Derived from the Blood
A special feature of glucose delivery to the neurons is that its transport through the cell membranes of the neurons does not depend on insulin. Even in patients who have serious diabetes glucose diffuses readily into the neurons. When a diabetic patient is overtreated with insulin, the blood glucose concentration can fall to an extremely low level because the excess insulin causes almost all of the glucose in the blood to be transported rapidly into the insulin-sensitive, nonneural cells throughout the body. When this happens, insufficient glucose is left in the blood to supply the neurons, and mental function can become seriously impaired, leading to mental imbalance, psychotic disturbances, and sometimes coma.