Review of Medical Physiology - William F. Ganong 2002

Circulation
Regional Circulation
Cerebral Circulation — Cerebral Blood Flow

The Kety Method

According to the Fick principle (see Chapter 29), Blood FLOW IN any organ can be measured by determining The amount of a specific substance (Q_x) removed from the bloodstream by the organ per unit of time, divided by the difference between the arterial and venous concentrations of that substance across the organ (A_x - V_x). Thus,

Class="center">

This can be measured clinically using N₂O inhalation (the Kety method). The average cerebral blood flow in young adults is 54 mL/100 g/min. Since the average adult human Brain weighs about 1400 g, the total cerebral blood flow is approximately 756 mL/min. It is important to note that while the Kety method provides average values for areas with normal perfusion, it yields no information on Regional Blood Flow differences. Furthermore, because it relies on N₂O uptake, it measures blood flow exclusively in well-perfused Regions of the brain. If blood flow to a specific area is compromised (such as in an occlusion), no change in blood flow measurements will be detected, as N₂O is not absorbed in non-perfused areas.

Regional Blood Flow in the Brain

A significant breakthrough in recent years has been The Development of techniques for monitoring regional blood flow in conscious, living subjects. Among the most advanced Methods are positron emission tomography (PET) and related technologies, which utilize short-lived isotopes to radiolabel a specific compound administered to the subject. The uptake and clearance of the labeled compound are tracked by an array of scintillation detectors positioned around the HEAD. Data from these detectors are processed by a computer and can be displayed on a screen or color monitor, where the color corresponding to each detector's Location is proportional to the local blood flow. Because blood flow is tightly coupled to metabolic rate, the local uptake of 2-deoxyglucose also serves as a reliable indicator of blood flow (see below and Chapter 8). By labeling 2-deoxyglucose with a short-lived positron emitter such as ¹⁸F, ¹¹C, or ¹⁵O, its concentration can be accurately measured in any region of the brain. Another vital technique is Magnetic Resonance imaging (MRI). MRI relies on the detection of resonance signals emitted by various Tissues within a magnetic field. Because deoxygenated Hemoglobin is paramagnetic, it alters the magnetic resonance signals originating from Blood Vessels. Consequently, the relative levels of oxygenated and deoxygenated hemoglobin can be determined to assess blood flow (functional magnetic resonance imaging; fMRI). Today, fMRI offers superior spatial resolution compared to PET.

At rest, average blood flow is 69 mL/100 g/min in the Gray matter, compared to 28 mL/100 g/min in the White matter. A fascinating feature of brain function is the remarkable Variability of local blood flow in response to changes in neural activity. Examples are shown in Figures 16-1 and 32-8. In conscious, resting subjects, the highest blood flow is observed in the premotor and frontal areas—regions associated with the Processing and analysis of external stimuli as well as higher cognitive activity. During a voluntary clenching of the right hand, blood flow increases in the hand representation area of the left motor cortex and the corresponding somatosensory areas of the postcentral gyrus. When execution involves sequential movements, blood flow increases within the supplementary motor areas. During speech, bilateral increases in blood flow are recorded in the sensory and motor regions governing the face, Tongue, and Oral Cavity, as well as in the upper premotor cortex of the dominant (usually left) hemisphere. If speech is stereotyped, Broca's and Wernicke's areas show no significant increase in blood flow; however, when speech is creative and involves novel ideas, blood flow increases in both regions. Reading induces widespread increases in blood flow. Problem-solving, reasoning, and motor imagery (mental rehearsal without actual movement) trigger elevated blood flow in specific regions of the premotor and frontal cortices. During cognitive tasks, many brain regions are activated in advance, as if the brain is constructing an internal model of the planned task. In right-handed individuals, blood flow to the left hemisphere is greater during verbal tasks, whereas blood flow to the right hemisphere predominates during spatial tasks.

PET and fMRI are widely used to study various neurological disorders. Hyperemia is observed in epileptic foci during seizures, whereas blood flow is depressed in other brain regions. Between seizures, blood flow in the foci may sometimes decrease, which can precipitate subsequent attacks. Patients with symptoms of agnosia (see Chapter 16) exhibit reduced blood flow in the parieto-occipital regions. In Alzheimer's disease, the earliest signs are a decline in metabolic rate and blood flow in the superior parietal cortex, which subsequently spreads to the temporal and frontal cortices. Notably, the pre- and postcentral gyri, Basal Ganglia, thalamus, Brainstem, and Cerebellum remain relatively spared. In Huntington's chorea, bilateral reductions in blood flow to the caudate Nucleus are detected even in the Cytology/cytology/16.html">Early stages of the disease. Unlike unipolar depression, bipolar affective disorder (manic-depressive illness) is characterized by a generalized reduction in cortical blood flow during the depressive phase. Evidence also suggests that in Schizophrenia, blood flow is reduced in the frontal and temporal lobes and the basal ganglia. In migraine sufferers experiencing an aura, a bilateral decrease in blood flow originates in the occipital cortex and spreads anteriorly to the temporal and parietal lobes.

Cerebrovascular Resistance

Cerebrovascular resistance (CVR) is defined as the cerebral perfusion pressure divided by the cerebral blood flow. CVR in the supine position can generally be calculated using the mean brachial arterial pressure (neglecting the relatively low cerebral venous pressure) without significant error. Calculated in this manner, normal CVR is approximately 10 R-units per kg of brain tissue (7,2 R-units for the entire brain) (see Table 32-1).