The mechanism of flow in a vascular bed are usually simplified to three concepts: (a) perfusion pressure (P), the pressure differential between the inflow side and the outflow side, (b) the resistance to flow (R) and (c) the resultant flow volume (F).
In the cerebral circulation, the CPP is the difference between the MABP and the ICP because the venous pressure inside the dura cannot possibly be lower than the ICP because of the collapsible walls of the veins.
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Fig. 1 Pressure-flow resistance graph: assuming CBF1 (cerebral blood flow) and CPP1 (cerebral perfusion pressure), we are using the dynamic linear curve R1 so that if pressure drops to CPP2, flow would drop an equal percentage amount to CBF2 indicated by the straight line. After some delay autoregulation becomes effective with, changing the resistance to curve R2, whereby flow is restored to very near its original value. The thick line indicates the static pressure-flow relationship that is a result of the cerebral autoregulation being effective within the horizontal portion (adapted from R Aaslid. Cerebral Hemodynamics. In Newell DW, Aaslid R: Transcranial Doppler, Raven Press, New York, 1992).
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The concept of the CVR is sometimes thought of as being borrowed from electrical theory (Ohm's law), but the basis for this concept is Hagen-Poiseuille's law for steady laminar flow in long cylindrical tubes:
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According to this concept, CBF at any time should be given by:
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The Hagen-Poiseuille equation predicts that the pressure-flow relationship goes through the origin. Assuming constant CVR, CBF and CPP would be perfectly proportional, going to zero with zero CPP (Fig. 1). For changes in the CPP so short-lasting that cerebral autoregulation or other factors changing the caliber of the resistance vessels do not react, this theory assumes that the relationship between CPP and CBF would be a linear one illustrated by the straight lines in the figure going toward the origin. This can be described as the dynamic cerebral pressure-flow relationship. In contrast, the static cerebral pressure-flow relationship is the familiar autoregulation curve illustrated by the thick line in the figure i.e. the horizontal portion of the pressure-flow curve. This allows CVR to change in order to compensate for variations in CPP. This is accomplished by a shift between the dynamic pressure-flow relationship lines. This model of dynamic and static changes covers both fast and slow aspects in the cerebral pressure-flow relationship. The dynamic pressure-flow curves are valid only for short time intervals when there is no change in vasomoter tone. The static pressure-flow curve, on the other hand, represents the pressure-flow relationship when sufficient time has elapsed so that the dynamic behavior of the autoregulation mechanism has settled down.
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Fig. 2 Pressure-flow graph: the thick line indicates the static pressure-flow relationship resulting from cerebral autoregulation being effective within its limits. The straight lines showing the dynamic pressure-flow relationship intercept the pressure axis at various levels of 'critical closing pressure' (adapted from R Aaslid. Cerebral Hemodynamics. In Newell DW, Aaslid R: Transcranial Doppler, Raven Press, New York, 1992).
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The real physiology of the vascular bed clearly is more complicated than these hydromechanical analogues used to derive the pressure-fow relationship of rigid tubes. Most of our knowledge about the cerebral circulation comes from studies using indicator methods. However, these techniques as outlined previously, are not capable of detecting and following the dynamic aspects of the pressure-flow relations. In addition, studies based on electromagnetic flowmeter recordings in animals have considerable doubt about the validity of the concept of a simple proportional CVR to explain the dynamic pressure-flow relationship. One complicating factor might be the volume compliance of the vascular bed; the basic discrepancy is that the pressure-flow lines do not go toward the origin but intercept the pressure axis at a variable pressure significantly above zero (Fig. 2). The intercept means that the simple relationship of a CVR as incorporated in the previous equation is not adequate. This has been well documented in the myocardial circulation, where the dynamic pressure-flow relationship is closely related to changes in vasomotor tone. It is therefore not surprising that the cerebral circulation - also being a high-flow vascular bed - exhibits approximately the same pressure-flow characteristics. The reason why flow stops at perfusion pressure significantly higher than zero is not known. This effect first was observed in 1951, and the intercept was labeled 'critical closing pressure'. The walls of the small resistance vessels that control flow consists mostly of smooth muscle. This muscle has its own rather complicated dynamics that may cause cessation of flow at low transmural pressures. Moreover, the flow-diameter relationship is strongly nonlinear because the red blood flow cells have practically the same size as the lumen of the vessels in the microcirculation.
The regulation of CBF is one of the most frequently debated topics in the neurophysiologic literature. Despite different techniques to quantify the degree to which various physiologic factors control or influence CBF, many controversies still remain. Generally it is agreed that at least four main mechanisms regulate CBF (Fig. 3).
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Fig. 3 Regulation of CBF (cerebral blood flow): the input variables are metabolic, external chemical, neurogenic and pressure factors. The system can be divided in three main blocks. The dynamic pressure-flow relationship, the balance between supply and demand in the cerebral tissue and the vascular smooth muscle regulating vasomotor tone.
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However, the exact importance of each mechanism and their relationships in normal and neurologically compromised patients have not yet been fully elucidated: (a) metabolic regulation; a considerable body of evidence suggests that CBF is dictated by local cerebral metabolic activity. As demand increases, flow increases and vice versa. The actual coupling mechanism is unknown. A proposed control mechanism include certain vasoactive compounds: biochemical mediators may be locally elaborated in response to metabolic activity, eg adenosine, potassium, prostaglandines etc. (b) external chemical regulation; the PaCO2 is considered to be the most important known vascular modulator in CBF. No other physiologic or pharmacologic factor is capable of producing changes of this magnitude. The PaO2 also has significant effects on the cerebrovasculature, but they are several orders of magnitude less than those for PaCO2. Hyperoxia produces mild vasoconstriction, whereas hypoxia produces marked vasodilation and increased CBF. (c) pressure regulation; cerebral pressure autoregulation, i.e. the static flow-pressure relationship, is defined as the maintenance of CPP over a wide range of MABP. In normal adults CPP is maintained over a wide gradient of MABP in the range of 60 to 160 mmHg and falls or increases linearly with changes in MABP, and (d) neurogenic regulation; the impact of sympathetic nervous system activity on CBF often is ignored. However, intense sympathetic activity will result in vasoconstriction, and can shift the cerebral autoregulatory curve to the right.