The Highs and Lows of Blood Pressure

Part I: Principles of Measurement and Basic Physiology of Arterial Pressure

Arterial blood pressure measurement is one of the most basic clinical acts performed by the healthcare workers, and minimal values are routinely prescribed for critically ill patients.^[1] Yet, the subtleties, determinants, and physiological role of blood pressure measurement often are not appreciated. Guidelines^[2] and review articles^[3,4] give recommendations for treatment when arterial pressure is below a minimum value, but these recommendations are based on little data. I will state from the outset that I am not able to provide an appropriate target pressure that should trigger a clinical intervention and I suspect that a specific pressure may not be the best choice. Rather decisions likely need to be based on constellations of physiological variables. However, clinicians still need some guiding principles for situations in which monitoring is limited to just a blood pressure measurement and there is a need to respond rapidly in a severely ill patient. Development of proper targets for blood pressure in patients with shock will require well-controlled and adequately powered empiric studies as has occurred for the management of high blood pressure, although it is also worth noting that current guidelines for hypertension did not come quickly. Initially targets were higher than current recommendations because there were concerns that lowering arterial pressure too aggressively could cause harm. Only careful long-term empiric studies eventually showed the efficacy and safety of current lower targets. The current targets for management of hypertension could not have been predicted from first principles.^[5] There is almost a complete lack of these kinds of controlled empiric studies for the low end targets of blood pressure, but the same process needs to occur. Furthermore, it is likely that minimal blood pressure targets will not be the same in sepsis, hypovolemia, or cardiogenic shock because of differences in their pathophysiology. In this article, I will attempt to lay the groundwork for the physiological principles that should be considered when planning empiric studies on blood pressure targets in shock. I will try to give clinicians approaches for the management of individual patients before well-developed empiric data become available. A number of reviews have addressed some of these issues,^[3,4,6] but this article will emphasize the importance of factors that determine arterial pressure, especially vascular resistance and its distribution among organs.

What is Blood Pressure?

Blood pressure is the force that distends the elastic walls of vessels. Physical measurements, including vascular pressure, are referenced relative to some value. Since our bodies are surrounded by atmospheric pressure, measurement of blood pressure (blood pressure is used as a simplification of arterial blood pressure) is presented as a deviation from atmospheric pressure, which is defined as the "zero" value. This means that a blood pressure of 120/80 mm Hg at sea level with an atmospheric pressure of approximately 760 mm Hg is actually 880/840 mm Hg. This actual value is obviously cumbersome and furthermore fluctuates with weather conditions. Blood pressure is thus normalized to atmospheric pressure which is the outside pressure for all regions of the body except structures in the chest. However, this simplification leads to important errors in the assessment of wall stress by the Laplace relationship, which says that wall stress is equal to the product of the pressure inside a vessel and the radius of the lumen of the vessel.^[7] The Laplace relationship only is valid for very thin-walled structures. When wall thickness is greater than a very small fraction of the radius, calculated wall stress actually has a negative value instead of the positive value obtained with the simplified Laplace approach.^[7,8]

Three types of energies determine measured vascular pressure: elastic, kinetic, and gravitational.^[9] In a supine subject, the gravitational component is small, but gravitational energy becomes a major factor when in the upright position. Not only are hydrostatic pressures measured relative to atmospheric pressure, but pressures also are relative to the "level" of the measuring device when pressure is measured with a fluid filled system. This is because the fluid column in the tubing has a mass and adds a nontrivial gravitational energy component to the measurement. The consensus position for the reference level for placement of the measuring device is the midpoint of the right atrium for that is where the blood comes back to the heart and is pumped out again. This can be estimated at the bedside at a point which is at a vertical distance of 5 cm below the sternal angle, which is where the second rib meets the sternum. This is valid at least up to a body angle of 60% from the horizontal.^[10] The actual pressure distending vessels, however, is very different in the head and the foot in an upright person. In a 180-cm person (~ 71 inches), the feet are about 120 cm below the heart and the top of the head is about 60 cm above the heart (Fig. 1). With a blood pressure at the level of the heart of 100 mm Hg, and density of blood of approximately 1 g/cm³, the actual pressure distending the arterial vessels in the foot is 183 mm Hg and at the top of the head it is 51 mm Hg. These values would be obtained if the transducer was leveled relative to the foot or head, respectively. It is worth noting that the added pressure produced by gravity in the foot of a standing person is close to the arterial pressure generated by the heart in a supine individual.

Measured intravascular pressure is also affected by the position and type of cannula used. Vessel walls are distended by elastic pressure, and this pressure is most accurately measured by a hole on the side of the cannula. If an end-hole catheter is used, and the hole faces the flow as in a standard arterial catheter, kinetic energy in the moving blood is lost as it hits the cannula. The kinetic energy then is converted into elastic energy so that the measured pressure is higher than the pressure measured with a side-hole catheter. Normally, kinetic energy only contributes about 4 mm Hg (3%) to peak arterial pressure and 0.35 mm Hg to mean arterial pressure,^[11] but the contribution from kinetic energy increases when pressure is low as in the vena cava and pulmonary systems, for although they have low elastic pressures, their mean velocity of blood flow is the same as the aorta. In hyperdynamic sepsis, the combination of increased blood velocity and low arterial pressure likely results in a greater contribution of kinetic energy to total energy which means that blood flow can be the same with a lower elastic pressure as measured by a cuff. Under normal flow conditions, pulse pressure is amplified when measured further away for the aorta although there is a slight decrease in mean pressure. On the other hand when there is marked vasoconstriction, a more peripheral pressure such as radial arterial pressure, may me be lower than femoral arterial pressure because there is a greater resistance drop due the constriction of the vessel. The end-whole femoral arterial pressure also has a greater kinetic component for the velocity is likely larger due to the smaller overall cross-sectional area at that level of the circulation. The message is that measured pressures will vary with site and hemodynamic state of the patient. Recommendations for pressure targets need to consider the site and method of measurement. Trends in pressure and the relationship to metabolic measures will likely be the most important indicators.

What Determines the Blood Pressure?

A worthwhile intellectual exercise is to consider whether arterial pressure determines cardiac output or whether cardiac output determines the arterial pressure. Intuitively people most often have a model in their minds in which the heart produces a force, that is pressure, which drives the blood around the circulation, and this view is still argued by some.^[12] However, it is actually the volume per time that the heart forces through the systemic vascular resistance that creates the arterial pressure.^[13] The pulsatile component of arterial pressure is obviously related to the cyclic contraction of the heart, but the determinants of the systolic and diastolic pressure are more complex. When the stroke volume is pumped into the elastic aorta, the aortic wall is stretched and some of the volume is transiently taken up by the aorta and then released during the rest of the cycle in what is known as the "Windkessel effect." Peak systolic pressure is thus determined by the amount of volume ejected by the heart per beat, that is, stroke volume, the elastic properties of the aortic wall, the initial volume in the aorta at the start of cardiac ejection, and the rate of outflow from the aorta. Because of phase shifts between flow and pressure, the frequency of cardiac contractions also affects the pressure. Peak systolic pressure is further complicated by reflected waves which occur when the forward wave hits bifurcations such as branching at the iliac arteries. The diastolic pressure is more dependent on the runoff from the aorta and large vessels which in turn are dependent on peripheral resistance, but it is also affected by the duration of the cardiac cycle and the initial volume in the aorta because aortic compliance is curvilinear. Paradoxically, although blood pressure does not determine cardiac output, arterial pressure is an important determinant of regional flows. However, this should not be confused with blood pressure being an indicator of regional flows.

Why is Arterial Pressure so High?

An important principle of mammalian cardiovascular physiology is that the vascular system is pressure regulated, which means that blood pressure normally is kept in a narrow range. Even during heavy aerobic exercise, systolic arterial pressure rises by less than 50% in healthy subjects. The pressure in most mammals tends to be regulated around 120/80 mm Hg. This relatively high value (at least compared with pulmonary arterial pressure) certainly cannot be because this pressure is required to move the blood through the body, for the right heart pumps the same amount of blood as the left heart through the lungs with a mean pressure of less than 20 mm Hg. Another thought might be that this high pressure is needed to overcome the gravitational loss of energy to the head and to maintain cerebral perfusion. However, blood pressures in rats and mice are similar to that of humans, but they do not have the same gravitational demands. The likely reasons for high arterial pressure in mammals are related to selective advantages for cardiac performance and the distribution of flow. Cardiac muscle handles volume work (i.e., muscle shortening) much more efficiently than pressure work. Thus, by keeping the arterial pressure relatively constant, the heart works against a relatively constant load. This design component can be appreciated when considering what is required to increase flow. For example, during maximal exercise in a standard size male, muscle blood flow can increase from around 2 to 3 L/min at rest to greater than 20 L/min. If systemic vascular resistance started very low, and resting arterial pressure was around 20 mm Hg, flow to the working muscle could not selectively increase much more by a local decrease in resistance for blood pressure would be even lower. Blood flow would have to increase to all regions and total flow blood flow would have to be much higher. A solution for this would be to constrict all nonworking regions, but surely from a design point of view, it is much easier to dilate the area that needs flow rather than constrict all the regions of the body that do not need as much flow. Furthermore, dilatation can occur through local metabolic mechanisms and does not require innervations of vessels, although the presence of neural inputs increases the efficiency of the system. Thus, the arterial system works much like a reservoir that supplies water to a community. The hydrostatic pressure in the tank is kept relatively constant by the height of the tank. Opening taps, which effectively decreases local resistances, allows water to flow to individual homes. However, although the arterial pressure is produced by the product of total cardiac output and total systemic vascular resistances of all regions of the body, regional flows are determined by the arterial pressure and their individual vascular resistances relative to other regions of the body. Thus, the distribution of local arterial resistances is the major determinant of where blood goes as will be discussed in the next section.

What is Resistance?

In an ideal flowing fluid, which is called a "Newtonian fluid," layers form in the flowing column because of the frictional loss of energy due to contact of the fluid with vessel walls and between the fluid layers. The potential of fluid layers to slide over each other is called "viscosity." This frictional loss of energy produces the pressure drop along the course of blood vessels which we refer to as the "resistance" to flow of the fluid. As determined by Poiseuille in the 19th century, flow is proportional to the length of the tube, proportional to the viscosity of the fluid, and most importantly, inversely proportional to the fourth power of the radius of the tube. Thus, vessel radius is the primary determinant of the resistance, and small changes in vessel radius produce large changes is vascular resistance. If the resistance to all vascular beds were the same, the flow would be the same in every region, but each vascular bed has its own resistance characteristics, which allows flow to vary among organs (Fig. 2), and this resistance can vary according to need for flow by changes in the radii of vessels.^[14] However, elastin and collagen of vessel walls set limits to how much vessels can dilate.^[15] Fully dilated vessels function as rigid pipes and flow becomes linearly related to the pressure difference between the inflow and outflow pressure. Maximal flow in each region is determined by the maximal inherent cross-sectional area of the vasculature in that bed. The vascular density and thus cross-sectional area of the vessels in the heart is much larger than that of skeletal muscle, and consequently, maximal coronary blood flow per gram of tissue at a given pressure is two to three times that in skeletal muscle (Fig. 3). The kidney, too, has a very large maximal flow per mass compared with other organs (Fig. 3).

There are some basic starting "rules" that help predict responses to challenges to the system under normal conditions. Regional flows are proportional to metabolic need so that for the whole body, and in individual organs, there is a tight linear relationship between cardiac output and oxygen consumption.^[16] The relationship is especially strong in muscle tissues but not very strong in the kidney. It is important to appreciate that it is total flow, that is, cardiac output, which is regulated in the body and not stroke volume.^[16] During exercise, heart rate increases in proportion to the relative demands of the workload compared to the capacity of the system.^[16] Since venous return and thus cardiac output during exercise are controlled by the total metabolic need of the body, and heart rate is controlled by the relative workload, stroke volume becomes a dependent variable. Neural inputs that increase heart rate without major metabolic changes, such as occur with anxiety or chronotropic drugs, decrease stroke volume without much change in cardiac output. Baseline distribution of flow is set by structural and neurohumeral mechanisms which maintain the arterial pressure at a relatively constant level with changes in blood flow. Arterial baroreceptors are the primary sensor for this process.

The baroreceptor response to changes in arterial pressure gives a good example of the hierarchy of the system. In severe hypotension, there is a disproportionately greater increase in the arterial resistance in muscle vasculature compared with that of the splanchnic circulation.^[17] This can be seen as an attempt to protect the metabolically active abdominal organs because the relatively greater increase in vascular resistance in muscle shifts a greater fraction of the limited blood flow to the splanchnic bed. This likely occurs due to differences in adrenergic receptor density. The implication is that actions of vasoactive drugs also will not be the same in all regions.

Distribution of flow to different vascular regions can overcome this hierarchy through three mechanisms: local metabolic activity, myogenic responses, and flow-mediated dilatation. Metabolic activity releases substances that vasodilate vascular smooth muscle. These include adenosine, potassium ions, increased osmolarity, low PO₂, PCO₂, lactate, and prostaglandins, but which one dominates is not known and they likely work together with varying sensitivities in different tissues.^[18–21] Exercise provides a good example of the interaction of local metabolic and neurogenic factors. During exercise, the drop in systemic vascular resistance and activation of peripheral afferent nerves^[22,23] lead to increased sympathetic tone and generalized constriction of vascular beds, but local metabolic factors in the working muscle and the heart counteract this constricting effect, and there is net vasodilation in these regions. This redirects flow to these working regions.

Certain regions of the body such as the brain and kidney do not have large changes in metabolic need but still depend on a relatively constant blood flow for normal function. A rise in pressure above normal would produce excessive cerebral blood flow, increase intracranial blood volume, and raise intracranial pressure. Too low pressure would jeopardize brain function. Furthermore, a rise in pressure could distend vascular walls which would decrease vascular resistance and result in even greater flow. This feed-forward process is prevented by changes in vascular tone in response to changes in arterial pressure in what is called the myogenic mechanism.^[24–27] This process is especially strong in the brain and kidney and keeps flow relatively constant over a wide range of pressures.

The third local regulator of regional flow is called "flow-mediated dilatation." An increase in flow increases a force on the endothelium that is called "shear stress." This increases basal release of nitric oxide from endothelial cells which dilates vascular smooth muscle.^[28,29] The process has the advantage of allowing upstream flow to better match downstream needs, but it also produces a feed-forward process which is kept in check through counter regulation by myogenic and metabolic mechanisms.

Local regulatory mechanisms are lost in sepsis, ischemia-reperfusion, and may be abnormal in patients with metabolic syndrome and vascular disease associated with endothelial dysfunction. This makes it very difficult to predict how vessels will respond to pharmacological agents and creates a major limitation for the use of a simple blood pressure measurement to guide therapy that is intended to increase regional flow.

Calculation of resistance with Poiseuille law is based on the difference between the inflow and outflow pressures. It would seem obvious that the outflow pressure in the vascular tree should be the lowest pressure in the system, which is the central venous pressure. However, this is not the case. There is flow limitation at the arteriolar level, which produces an effective critical closing pressure or "vascular waterfall"^[30,31] (Fig. 4). When there is flow limitation, flow is determined by the difference between the arterial and critical closing pressures and not the final downstream pressure. The implications of this are very significant for the interpretation of systemic vascular resistance. The mean critical closing pressure for the whole body is estimated to be in the range of 25–30 mm Hg^[32] but varies among tissues, and values as high as 60–70 mm Hg have been found in the resting hindlimb of dogs^[31,33] (Fig. 4). The standard calculation of systemic vascular resistance is based on the difference between arterial and central venous pressure instead of the critical closing pressure because the critical closing pressure cannot be clinically measured. Use of this incorrect downstream pressure produces an error that gets progressively larger the lower the inflow pressure because the error makes up a larger fraction of total pressure. As a result, there is an "apparent" decrease in resistance with increases in pressure or flow. It is physiologically plausible that the arterial resistance falls with an increase in pressure for this would be expected from baroreceptor-mediated regulation of arterial pressure, but the standard calculated resistance will fall whether or not there is a change in the true resistance (Fig. 5). This artifact only can be ruled out by obtaining 2 points on the pressure-flow relationship, but this cannot readily be obtained in intact persons. The consequence of this is that a drug that effectively increases cardiac output, such as the phosphodiesterase inhibitor milrinone, will appear to do so by reducing vascular resistance and afterload, but these cannot be separated from a change in contractility without 2 points on a pressure-flow line.

The presence of critical closing pressures at the arteriolar level means that arterial pressure can be regulated in two ways: one is by a change in the actual resistance, which is the inverse of the slope of the pressure-flow relationship, and the other is by changes in critical closing pressures, which is the x-intercept. If pressure rises due to an increase in resistance, a given change in flow will produce a greater change in pressure, but if the rise in pressure is due to a change in critical closing pressure, a subsequent change in flow will produce the same change in pressure as occurred before the increase in the critical closing pressure. Of historical interest, critical closing pressures are also called "Starling resistors" because Ernest Starling used floppy collapsible tubes to produce a critical closing pressure in the circuit of his heart-lung preparation and was thereby able to maintain a constant pressure against which the heart contracted. The critical closing pressure in our vasculatures likely serves a similar function. Disease states can alter critical closing pressure, and this adds a further level of complexity to the system.^[33–37] The clinical implication of the intrinsic error in the standard calculation of vascular resistance is that changes in calculated resistance have little meaning and one should instead examine the directional changes in arterial pressure and cardiac output.

Crit Care Med. 2014;42(5):1241-1251. © 2014  Lippincott Williams & Wilkins