Central Nervous System Physiology: Cerebrovascular

Arteries and Arterioles

The cerebral arteries distributing flow from the circle of Willis continuously branch into smaller arteries and arterioles that course along the surface of the brain. At their distal end, before entering the brain parenchyma, they are known as leptomeningeal vessels. The leptomeningeal vessels are found within the pia-arachnoid membrane and are surrounded by cerebral spinal fluid (CSF). The highly branched pial arterioles form an extensive collateral network on the surface of the brain before giving rise to a relatively unbranched system of penetrating intraparenchymal arterioles.

Venous Circulation

The venous circulation consists of an interconnected system of veins and sinuses. Venous outflow from the cerebral hemispheres occurs via cortical veins within the pia mater on the surface of the brain as well as deep central veins. Cortical and deep veins may empty into the superior sagittal sinus. Deep veins may also empty into either the inferior sagittal sinus or great vein of Galen. Venous flow is directed toward a confluence of sinuses (torcular herophili) then on toward the central circulation via the transverse sinus, sigmoid sinus, and jugular vein ( Fig. 9.3 ). Cerebellar drainage occurs primarily via the inferior cerebellar veins and occipital sinuses. Extensive collateralization between cortical veins as well as the deep veins and sinuses can augment venous drainage when primary routes are compromised.

Anterior Circulation

The anterior circulation arises from the intracranial extension of the internal carotid arteries. The most prominent branches of the anterior circulation are the anterior cerebral, middle cerebral, and posterior communicating (PCom) arteries. The PCom provides communication with the posterior circulation through direct connection with the posterior cerebral artery (PCA). An absent or hypoplastic PCom potentially compromises collateral flow between the anterior and posterior circulations. Likewise, collateral flow between the left and right anterior circulation can be compromised by a hypoplastic or aplastic anterior communicating (ACom) artery.

Posterior Circulation

The posterior circulation arises from paired vertebral arteries. At their rostral end, the vertebral arteries typically join together on the anterior surface of the brainstem to form the basilar artery. The vertebral and basilar arteries have multiple branches that supply the thalami, brainstem, cerebellum, and spinal cord. The basilar artery branches distally into the left and right PCAs. The branches of the PCA provide blood flow to the thalami, brainstem, choroid plexus, and cerebrum (occipital and portions of parietal and temporal lobes see Fig. 9.2A, B ) and provide a point of connection with the anterior circulation. Like the anterior circulation, there are many anatomic variants that may compromise collateral blood flow and predispose to ischemia in various clinical scenarios.

Cerebral Metabolic Rate

CMR is directly proportional to neuronal activity. Although the mechanism is not entirely understood, an increase in neuronal activity and CMR is tightly coupled to increased CBF. This physiologic process, wherein blood flow and metabolism are matched, is referred to as flow-metabolism coupling. The cellular mechanisms involved continue to be investigated, but likely involve processes mediated by a combination of neuronal activity and metabolic by-products, glial integration and modulation of neuronal synaptic activity, and vascular factors. Specific by-products of metabolism considered influential in this process include potassium ions (K ⁺ ), hydrogen ions (H ⁺ ), calcium ions (Ca ²⁺ ), lactate, adenosine, ATP, and nitric oxide (NO). Glia are in direct contact with both neurons and capillaries, and mounting data highlight the role of glia as a likely conduit for coupling neuronal activity with regional blood flow ( Fig. 9.4 ). Cerebral vessels are also densely innervated, and peptidergic neurotransmitters released by nerves also contribute to vascular regulation and flow-metabolism coupling. In the neurosurgical and critical care environments, CMR is influenced by the functional state of the nervous system, anesthetic agents, and temperature.

Functional State

CMR decreases during sleep and increases during sensory stimulation, mental tasks, or arousal of any cause. CMR is markedly increased during epileptic activity and substantially reduced in coma.

Anesthetic Agents

In general, with the exception of ketamine and nitrous oxide (N ₂ O), anesthetics suppress CMR. Specifically, the component of CMR related to electrophysiologic function is reduced. With several agents, including barbiturates, isoflurane, sevoflurane, desflurane, propofol, and etomidate, increasing plasma concentrations cause progressive suppression of EEG activity with a concomitant reduction in CMR. However, increasing the plasma level beyond that required to achieve suppression of the EEG results in no further CMR reduction. The component of CMR related to basic cellular homeostatic activities is unaffected by anesthetics ( Fig. 9.5 ).

Temperature

CMR decreases by 6% to 7% per degree Celsius of temperature reduction, and can cause complete suppression of the EEG at about 18°C to 20°C. In contrast to anesthetic agents, temperature reduction beyond that at which EEG suppression first occurs does produce a further decrease in CMR. This occurs because hypothermia decreases the rate of energy utilization associated with both electrophysiologic function and basal maintenance of cellular integrity ( Fig. 9.6 ). These decreases were once assumed to be proportional, but subsequent data demonstrate preferential suppression of the basal component (with mild hypothermia). The global cerebral metabolic rate of oxygen (CMRO ₂ ) at 18°C is less than 10% of normothermic control values, which likely accounts for the brain's tolerance of circulatory arrest for moderate periods at these temperatures.

Hyperthermia leads to substantial increases in CMR and CBF. However, above 42°C a dramatic reduction in CMRO ₂ occurs, possibly owing to neuronal injury and protein denaturation.

Paco ₂

CBF varies directly with Pa co ₂ ( Fig. 9.7 ). For each change of 1 mm Hg in Pa co ₂ from normal values, CBF changes 1 to 2 mL/100 g per minute. This response is attenuated outside the physiologic range of about 20 to 80 mm Hg and is sensitive to the baseline CBF. For example, hyperventilation causes a greater reduction in CBF when the resting CBF is high (as can occur with volatile anesthetics), an effect that is attenuated with lower resting CBF. Therefore anesthetic agents have the capacity to alter CO ₂ responsiveness of the cerebral circulation by changing basal CBF.

The changes in CBF caused by Pa co ₂ depend on the pH in the extracellular fluid of the brain. Extracellular pH and CBF changes occur rapidly after Pa co ₂ adjustments because CO ₂ (neutral charge) diffuses freely across the cerebrovascular endothelium. In contrast, acute systemic metabolic acidosis has little immediate effect on CBF because the blood-brain barrier (BBB) excludes H ⁺ from the perivascular space.

Although changes to CBF induced by Pa co ₂ are rapid, they are not sustained. Despite maintenance of increased arterial pH (through hyperventilation), CBF returns toward baseline over 6 to 18 hours because CSF pH gradually normalizes through bicarbonate extrusion ( Fig. 9.8 ). Therefore patients with sustained periods of hyperventilation or hypoventilation deserve special consideration. Acute normalization of Pa co ₂ results in a significant CSF acidosis (after hypocapnia) or alkalosis (after hypercapnia). The former results in increased CBF with a concomitant increase in intracranial pressure (ICP), depending on the prevailing intracranial elastance. The latter conveys the theoretical risk of ischemia.