Determinations of the regional distribution of PBF have shown that gravity is another important “passive” factor affecting local PVR and the relative perfusion of different regions of the lung. The interaction of the effects of gravity and extravascular pressures may have a profound influence on the relative perfusion of different areas of the lung.
Measurement of Total Pulmonary Blood Flow
The total PBF (which is the cardiac output) can be determined clinically in several ways, the more accurate of which have the disadvantage of being invasive to the patient (ie, requiring minor surgery).
Both arterial and mixed venous (which is equal to pulmonary artery) blood must be sampled in this method. Central venous oxygen saturation (SO2 see Chapter 7) is sometimes used to calculate the approximate mixed venous oxygen content because central venous blood is much easier to obtain than mixed venous—a catheter in the pulmonary artery is not necessary. A low central venous oxygen saturation is also a good indicator of poor tissue oxygenation and may be more useful clinically than determination of the cardiac output.
The Indicator Dilution Technique
In this traditional method, no longer used commonly, a known amount of an indicator dye that stays in the blood vessels, such as indocyanine green, is injected intravenously as a bolus. The systemic arterial dye concentration is monitored continuously with a densitometer as the dye passes through the aorta. Correction must be made for recirculating dye because the concentration change of interest is that which occurs in a single pass through the pulmonary circulation. A curve of the dye concentration as it changes with time is constructed, and then the area under the curve is determined by integration. Dividing this amount by the time of passage of the dye gives the average concentration of dye through the passage. If the cardiac output is high, the dye concentration falls rapidly, and so the area under the curve is small and the average dye concentration is low. If the cardiac output is low, the area under the curve is large and the average dye concentration is high. The cardiac output () is equal to the amount of dye injected in milligrams (I) divided by the mean dye concentration in milligrams per milliliter (c) times the time of passage (t) in seconds:
The calculations are usually done automatically in newer densitometers. Both arterial and venous catheters are necessary for this technique.
The Thermal Dilution Technique
This method is similar in principle to the indicator dilution technique. Cold fluid, for example, saline, is injected into a central vein, and the change in temperature of the blood downstream is monitored continuously with a thermistor. With high cardiac outputs, the temperature returns to normal rapidly; with low cardiac outputs, the temperature rises slowly. The advantage of this method is that the insertion of a single intravenous catheter is the only necessary surgical procedure. A type of catheter known as a quadruple-lumen Swan-Ganz catheter is used. One lumen is connected to a tiny inflatable balloon at the end of the catheter. During the insertion of the catheter, the balloon is inflated so that the tip of the catheter “floats” in the direction of blood flow: through the right atrium and ventricle and into the pulmonary artery. The balloon is then deflated. A second lumen carries the thermistor wire to the end of the catheter. A third lumen travels only part of the way down the catheter so that it opens into a central vein. This lumen is used for the injection of the cold solution. The final lumen, at the end of the catheter, is open to the pulmonary artery, and it allows pulmonary artery pressure to be monitored. (It can also be used to sample mixed venous blood.) This monitoring is necessary because the only way the physician knows that the catheter is placed properly is by recognizing the characteristic pulmonary artery pressure trace (unless a fluoroscope is used).
The temperature change after the injection is monitored by a cardiac output “computer” that automatically calculates the cardiac output from the volume and temperature of the injected substance, the original blood temperature, and the temperature change of the blood with time.
If the Swan-Ganz catheter is advanced, with the balloon inflated, until it completely occludes a branch of the pulmonary artery, it is said to be “wedged.” The pressure measured at the tip of the catheter with the balloon still inflated is approximately equal to the pressure in the vascular segment immediately distal to it, the pulmonary capillary pressure. Because there are no valves between the pulmonary capillaries and the lumen of the left atrium, this “pulmonary capillary wedge pressure” is similar to left atrial pressure. When the balloon is deflated, the pressure measured at the tip of the catheter is pulmonary artery pressure. Figure 4–7 shows a pressure trace as a Swan-Ganz catheter is advanced through the right atrium, the right ventricle, the main pulmonary artery, and into a branch of the pulmonary artery until it is “wedged.” The balloon is then deflated to show pulmonary artery pressure.
Pressure trace obtained from an anesthetized dog as a Swan-Ganz catheter is advanced through the right atrium, the right ventricle, through the main pulmonary artery, and into a branch of the pulmonary artery until it is “wedged.” The balloon is then deflated to show pulmonary artery pressure. Pulmonary capillary wedge pressure was about 8 mm Hg, and mean pulmonary artery pressure was about 17 mm Hg.
Several methods can be used to determine cardiac output noninvasively: some are currently used clinically; others are used experimentally. They include transcutaneous and transesophageal Doppler ultrasonography, thoracic electrical bioimpedance, pulse pressure waveform analysis, and partial CO2 rebreathing. The Doppler ultrasonography methods are more commonly used clinically.
Determination of Regional Pulmonary Blood Flow
Regional PBF can be determined by pulmonary angiography, by lung scans after injection of macroaggregates of albumin labeled with radioactive iodine (131I) or technetium (99mTC), and by lung scans after the infusion of dissolved radiolabeled gases such as 133Xe.
A radiopaque substance is injected into the pulmonary artery, and its movement through the lung is monitored during fluoroscopy. Unperfused areas secondary to vascular obstruction by emboli or from other causes are evident because none of the radiopaque substance enters these areas.
Macroaggregates of Albumin
Macroaggregates of albumin labeled with 131I or 99mTC in the size range of 10 to 50 μm are injected in small quantities into a peripheral vein. Most of these become trapped in small pulmonary vessels as they enter the lung. Lung scans for radioactivity demonstrate the perfused areas of the lung. The aggregates fragment and are removed from the lung within a day or so.
133Xe is dissolved in saline and injected intravenously. Xenon is not particularly soluble in saline or blood, and so it comes out of solution in the lung and enters the alveoli. If the 133Xe is well mixed in the blood as it enters the pulmonary artery, then the amount of radioactivity coming into a region of the lung is proportional to the amount of blood flow to that area. By making corrections for regional lung volume, the blood flow per unit volume of a region of the lung can be determined.
The Regional Distribution of Pulmonary Blood Flow
If 133Xe is used to determine regional PBF in a person seated upright or standing up, a pattern like that shown in Figure 4–8 is seen. There is greater blood flow per unit volume (“per alveolus”) to lower regions of the lung than to upper regions of the lung. Note that the test was made with the subject at the total lung capacity.
Relative blood flow per alveolus (100% = perfusion of each alveolus if all were perfused equally) versus distance from the bottom of the lung in a human seated upright. Measurement of regional blood flow was determined using an intravenous injection of 133Xe. TLC = total lung capacity. (Redrawn from Hughes, 1968, with permission.)
If the subject lies down, this pattern of regional perfusion is altered so that perfusion to the anatomically upper and lower portions of the lung is roughly evenly distributed, but blood flow per unit volume is still greater in the more gravity-dependent regions of the lung. For example, if the subject were to lie down on his or her left side, the left lung would receive more blood flow per unit volume than would the right lung. Exercise, which increases the cardiac output, increases the blood flow per unit volume to all regions of the lung, but the perfusion gradient persists so that there is still relatively greater blood flow per unit volume in more gravity-dependent regions of the lung.
The reason for this gradient of regional perfusion of the lung is obviously gravity. As already discussed, the pressure at the bottom of a column of a liquid is proportional to the height of the column times the density of the liquid times gravity. Thus, the intravascular pressures in more gravity-dependent portions of the lung are greater than those in upper regions. Because the pressures are greater in the more gravity-dependent regions of the lung, the resistance to blood flow is lower in lower regions of the lung owing to more recruitment or distention of vessels in these regions. It is therefore not only gravity but also the special characteristics of the pulmonary circulation that cause the increased blood flow to more gravity-dependent regions of the lung. After all, the same hydrostatic effects occur to an even greater extent in the left side of the circulation, but the thick walls of the systemic arteries are not affected. Blood travels through the more gravity-dependent regions of the lung at a faster rate. That is, the mean capillary transit time is less in the lower regions of the lung. There is also considerable heterogeneity in PBF at any vertical distance up the lung. That is, there may be significant variations in PBF within a given horizontal plane of the lung. These variations are caused by local factors and mechanical stresses.
The Interaction of Gravity and Extravascular Pressure: The Zones of the Lung
Experiments done on excised, perfused, upright animal lungs have demonstrated the same gradient of increased perfusion per unit volume from the top of the lung to the bottom. When the experiments were done at low pump outputs so that the pulmonary artery pressure was low, the uppermost regions of the lung received no blood flow. Perfusion of the lung ceased at the point at which alveolar pressure (PA) was just equal to pulmonary arterial pressure (Pa). Above this point, there was no perfusion because alveolar pressure exceeded pulmonary artery pressure, and so the transmural pressure across capillary walls was negative. Below this point, perfusion per unit volume increased steadily with increased distance down the lung.
Thus, under circumstances in which alveolar pressure is greater than pulmonary artery pressure in the upper parts of the lung, no blood flow occurs in that region, and the region is referred to as being in zone 1, as shown in Figure 4–9. (Note that in this figure blood flow is on the x-axis and that distance up the lung is on the y-axis.) Any zone 1, then, is ventilated but not perfused. It is alveolar dead space. Fortunately, during normal, quiet breathing in a person with a normal cardiac output, pulmonary artery pressure, even in the uppermost regions of the lung, is greater than alveolar pressure, and so there is no zone 1. Some experiments have also demonstrated perfusion of the corner vessels under zone 1 conditions.
The zones of the lung. The effects of gravity and alveolar pressure on the perfusion of the lung. Described in text. (Redrawn from West, 1964, with permission.)
The lower portion of the lung in Figure 4–9 is said to be in zone 3. In this region, the pulmonary artery pressure and the pulmonary vein pressure (Pv) are both greater than alveolar pressure. The driving pressure for blood flow through the lung in this region is simply pulmonary artery pressure minus pulmonary vein pressure. Note that this driving pressure stays constant as one moves further down the lung in zone 3 because the hydrostatic pressure effects are the same for both the arteries and the veins.
The middle portion of the lung in Figure 4–9 is in zone 2. In zone 2, pulmonary artery pressure is greater than alveolar pressure, and so blood flow does occur. However, because alveolar pressure is greater than pulmonary vein pressure, the effective driving pressure for blood flow is pulmonary artery pressure minus alveolar pressure in zone 2. (This is analogous to the situation during dynamic compression of the airways described in Chapter 2: During a forced expiration the driving pressure for airflow is equal to alveolar pressure minus intrapleural pressure.) Notice that in zone 2 (at right in Figure 4–9) the increase in blood flow per distance down the lung is greater than it is in zone 3. This is because the upstream driving pressure, the pulmonary artery pressure, increases according to the hydrostatic pressure increase, but the effective downstream pressure, alveolar pressure, is constant throughout the lung at any instant.
To summarize then: In zone 1,
and there is no blood flow (except perhaps in “corner vessels,” which are not exposed to alveolar pressure); in zone 2,
and the effective driving pressure for blood flow is Pa − PA; in zone 3,
and the driving pressure for blood flow is Pa − Pv.
It is important to realize that the boundaries between the zones are dependent on physiologic conditions—they are not fixed anatomic landmarks. Alveolar pressure changes during the course of each breath. During eupneic breathing these changes are only a few centimeters of water, but they may be much greater during speech, exercise, and other conditions. A patient on a positive-pressure ventilator with PEEP may have substantial amounts of zone 1 because alveolar pressure is always high. Similarly, after a hemorrhage or during general anesthesia, PBF and pulmonary artery pressure are low and zone 1 conditions are also likely. During exercise, cardiac output and pulmonary artery pressure increase and any existing zone 1 should be recruited to zone 2. The boundary between zones 2 and 3 will move upward as well. Pulmonary artery pressure is highly pulsatile, and so the borders between the zones probably even move up a bit with each contraction of the right ventricle.
Changes in lung volume also affect the regional distribution of PBF and will therefore affect the boundaries between zones. Finally, changes in body position alter the orientation of the zones with respect to the anatomic locations in the lung, but the same relationships exist with respect to gravity and alveolar pressure.