Pulmonary Vascular Resistance

Although the pulmonary circulation handles the same cardiac output from the right ventricle as the systemic circulation handles from the left ventricle, the former operates under much lower pressures and has substantially less resistance to flow than the latter. The systolic and diastolic pressures in the pulmonary artery normally are approximately 25 and 10 mm Hg, respectively, in contrast to 120 and 80 mm Hg in the systemic arteries. The pulmonary vascular resistance (PVR) can be calculated according to Equation 12-1:

The change or drop in pressure across the pulmonary circuit is the mean pulmonary artery pressure (mPA) minus the mean left atrial pressure (mLA), and the flow is the cardiac output (Equation 12-2). Thus:

Left atrial pressure is difficult to measure directly. However, a special catheter designed for this purpose, called a pulmonary artery balloon occlusion catheter or Swan-Ganz catheter, has been used widely in clinical application for such pressure measurements (Fig. 12-1). This catheter is inserted into a large vein (usually in the neck or groin) and passed through the right heart into a pulmonary artery. The catheter tip is equipped with a tiny soft balloon that lodges in a segmental pulmonary artery and temporarily blocks flow to the segment. After a short period of equilibration, because there is no blood flow passing the catheter tip, the pressure measured at the tip of the catheter reflects the pressure “downstream” in the pulmonary veins and left atrium.

Assuming normal mean pulmonary artery (PA) and left atrial (LA) pressures of 15 and 6 mm Hg, respectively, along with a cardiac output of 6 L/min, the pulmonary vascular resistance is (15 − 6)/6 mm Hg/L/min = 1.5 mm Hg/L/min. This resistance is approximately one tenth that found in the systemic circulation. (A source of confusion is that PVR may be reported in either Hg/L/min [also called Wood units] or in dyn·s/cm⁵. The value in Wood units is multiplied by 80 to convert to dyn·s/cm⁵.)

When cardiac output increases (e.g., during exercise), the pulmonary circulation is able to decrease its resistance and handle the extra flow with only a minimal increase in pulmonary artery pressure. Two mechanisms appear to be responsible: recruitment of vessels that had not been perfused at rest and, to a lesser extent, distention of previously perfused vessels. Under normal resting conditions, some pulmonary vessels receive no blood flow but are capable of carrying part of the pulmonary blood flow should the pressure increase. In addition, because pulmonary vessels have relatively thin walls, they are distensible and can enlarge their diameter under increased pressure to accommodate additional blood flow. With a means for increasing the total cross-sectional area of the pulmonary vasculature on demand, the pulmonary circulation is capable of lowering its resistance when the need for increased flow arises.

Another factor that affects PVR is lung volume. In discussing the nature of this effect, it is useful to distinguish two categories of pulmonary vessels on the basis of their size and location. One category, called alveolar vessels, includes the capillary network coursing through alveolar walls. When alveoli are expanded and lung volume is raised, these vessels are compressed within the stretched alveolar walls, and their contribution to PVR is increased. In contrast, when alveoli are emptied and lung volume is lowered, the resistance of these alveolar vessels is diminished. The other category consists of the larger vessels called extraalveolar vessels. They are not compressed by air-filled alveoli. The supporting structure that surrounds the walls of these vessels has attachments to alveolar walls, and the elastic recoil of the alveolar walls provides radial traction to keep these vessels open. This concept is similar to the concept discussed in Chapter 6 concerning the effect of alveolar wall attachments on airway diameter (see Fig. 6-6). When lung volume is increased, elastic recoil of the alveolar walls is increased, and the extraalveolar vessels become larger. When lung volume is decreased, the resistance of the extraalveolar vessels increases. This differential effect of lung volume on the resistance of alveolar versus extraalveolar vessels is shown in Figure 12-2. The total PVR is least at the normal resting expiratory position of the lung (i.e., at functional residual capacity).

Distribution of Pulmonary Blood Flow

The relatively low pressures in the pulmonary arteries have important implications regarding the way blood flow is distributed in the lung. When a person is in the upright position, blood going to the upper zones of the lung is flowing against gravity and must be under sufficient pressure in the pulmonary artery to make this antigravitational journey. Because the top of the lung is approximately 15 cm above the level of the main pulmonary arteries, a pressure of 15 cm H₂O is required to achieve perfusion of the apices. The mPA of 15 mm Hg (approximately 19 cm H₂O) is normally just sufficient to achieve flow to this region. In contrast, flow to the lower lung zones—that is, below the level of the main pulmonary arteries—is assisted by gravity. Therefore, in the upright individual, gravity provides a normal gradient of blood flow from the apex to the base of the lung, with the base receiving substantially greater flow than the apex (see Fig. 1-4). As discussed in Chapter 1, this distribution of blood flow in the lung has major implications regarding the manner in which ventilation and perfusion are matched.

The three-zone model for describing the determinants of pulmonary blood flow discussed in Chapter 1 actually is more complicated now that a zone 4 has been recognized. In this zone, which occupies the base of the lung at low lung volumes, blood flow progressively diminishes as the most dependent region of the lung is approached. To explain why a zone 4 exists, we must return to the concept of extraalveolar pulmonary vessels. At the lung bases, the weight of the lung results in decreased alveolar volume, accompanied by distortion and compression of extraalveolar vessels. As a result, the resistance of the extraalveolar vessels increases considerably, the total vascular resistance in this zone increases, and blood flow diminishes.

The distribution of blood flow in the lung can be measured with radioactive isotopes. A perfusion scan is a particularly useful technique that involves intravenous injection of radiolabeled particles, specifically macroaggregates of albumin, that are of sufficient size to lodge in the pulmonary capillaries. An external counter over the lung records the distribution of lodged particles and hence the distribution of blood flow to the lung. This technique, when performed in the upright individual, not only confirms the expected gradient of blood flow in the lung but also detects regions of decreased or absent perfusion in disease states such as pulmonary embolism (see Chapter 3).

Pulmonary Vascular Response to Hypoxia

An important physiologic feature of the pulmonary circulation is its response to hypoxia. When alveoli in an area of lung contain gas with a low PO₂, generally less than 60 to 70 mm Hg, the vessels supplying that region of lung undergo vasoconstriction. This response occurs primarily at the level of the small arteries or arterioles and serves as a protective mechanism for decreasing perfusion to poorly ventilated alveoli. Hence, ventilation-perfusion mismatch is decreased, and blood flow to areas with a low ventilation-perfusion ratio, which contribute hypoxemic blood, is minimized. When localized regions of lung have a low PO₂, the vasoconstrictive response also is localized. In these circumstances, the overall PVR does not increase significantly. However, with a more generalized decrease in PAO₂, as in many forms of lung disease or in persons exposed to high altitude, pulmonary vasoconstriction also is more generalized. In this circumstance, PVR and pulmonary artery pressure both are increased. What would be a protective response in the case of localized disease is thus detrimental in the case of generalized disease and widespread alveolar hypoxia.

There is one setting in which such generalized pulmonary vasoconstriction in response to alveolar hypoxia is most beneficial: the fetus. In utero, the alveoli receive no aeration, making the entire lung hypoxic. The result is marked pulmonary vasoconstriction, accompanied by very high PVR and diversion of blood away from the lung. Blood preferentially flows through the foramen ovale from the right to the left atrium and through the ductus arteriosus from the pulmonary artery to the aorta. This allows the majority of the blood oxygenated by the placenta to go directly into the systemic circulation of the fetus.

At birth, when the first few breaths are taken, the lungs expand and oxygen flows into the alveoli. The PVR falls, allowing blood to flow into the lungs. The fall in PVR is due to both the reversal of diffuse hypoxic pulmonary vasoconstriction and the mechanical effects of the inflated lung helping to open previously compressed vessels. As a result of this pulmonary vasodilation (as well as constriction of the ductus arteriosus), right ventricular output passes through the lungs, where the blood is oxygenated. Interestingly, the hypoxic vasoconstriction that persists throughout adult life may be directly related to this important fetal response.

The mechanism of hypoxic vasoconstriction is incompletely understood. One theory suggests that alveolar hypoxia is sensed by a redox sensor in the endothelial mitochondria, which generates a diffusible mediator—likely a reactive oxygen species. The mediator then acts on pulmonary vascular smooth muscle cells by inhibiting a membrane potassium ion channel, which leads to membrane depolarization and subsequent influx of calcium ions. The increase in intracellular calcium then induces pulmonary vascular smooth muscle cell contraction. Alternatively, hypoxia may alter release of vasoactive mediators; popular candidates are mediators released from vascular endothelial cells, such as the vasodilating factors nitric oxide (previously called endothelial-derived relaxing factor) and endogenously derived carbon monoxide, as well as the constricting factor known as endothelin. Nitric oxide, which is produced by vascular endothelial cells, acts via increasing cyclic guanosine monophosphate to produce vascular smooth muscle relaxation.

Other Aspects of Pulmonary Vascular Physiology

An additional stimulus for pulmonary vasoconstriction is a low blood pH value. Although this effect is less important than the effect of hypoxia, the two stimuli appear to have a synergistic effect on increasing PVR. Any effect of PCO₂ on the pulmonary vasculature appears to be small. Although hypercapnia may increase PVR, the effect apparently is mediated by changes in blood pH.

A variety of other factors that influence pulmonary vascular tone are being increasingly recognized. Autonomic innervation of the pulmonary arterial system is present but not extensive. Sympathetic and parasympathetic stimulation have the expected opposing effects, causing vasoconstriction and vasodilation, respectively. Humoral stimuli altering vascular tone are numerous; examples include histamine and the prostaglandin products of arachidonic acid metabolism. Most recently, interest has focused on two molecules mentioned earlier in the discussion of hypoxic vasoconstriction, each of which is known to have important effects on the pulmonary vasculature: nitric oxide (a potent vasodilator) and endothelin (a potent vasoconstrictor). Recognition of the role of these vasoactive compounds in the pathophysiology of disease states involving the pulmonary vasculature has led to development of drugs targeting these actions that have therapeutic benefits in patients with pulmonary arterial hypertension (see Chapter 13).

Another important aspect of pulmonary vascular physiology relates to fluid movement from pulmonary capillaries into the interstitium of the alveolar wall. Because of the importance of abnormalities in fluid transport across the capillaries in acute respiratory distress syndrome and respiratory failure, this topic is discussed specifically in Chapter 28.

Finally, although transport of blood between the heart and lungs is the most obvious function of the pulmonary vasculature, these vessels have other, nonrespiratory, metabolic functions. The pulmonary circulation has an important role in the inactivation of certain circulating bioactive chemicals. For example, serotonin (5-hydroxytryptamine) and bradykinin are primarily inactivated in the lung, probably at the level of the vascular endothelium. In addition, angiotensin I, an inactive decapeptide derived in the kidney, is converted to the active octapeptide angiotensin II by angiotensin-converting enzyme, which is produced by pulmonary vascular endothelial cells. Although the metabolic functions of the pulmonary vasculature are important in modifying the effects of these substances, whether derangements in these functions are important consequences of diseases affecting the vasculature is not yet known.

Browning, EA, Chatterjee, S, Fisher, AB. Stop the flow: a paradigm for cell signaling mediated by reactive oxygen species in the pulmonary endothelium. Annu Rev Physiol. 2012;74:403–424.

Fishman, AP. A century of pulmonary hemodynamics. Am J Respir Crit Care Med. 2004;170:109–113.

Keith, IM. The role of endogenous lung neuropeptides in regulation of the pulmonary circulation. Physiol Rev. 2000;49:519–537.

Mazza, E, Taichman, DB. Functions and control of the pulmonary circulation. In: Mandel J, Taichman DB, eds. Pulmonary vascular disease. Philadelphia: Saunders Elsevier, 2006.

Sommer, N, Dietrich, A, Schermuly, RT, et al. Regulation of hypoxic pulmonary vasoconstriction: basic mechanisms. Eur Respir J. 2008;32:1639–1651.

Stenmark, KR, Fagan, KA, Frid, MG. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res. 2006;99:675–691.

Weibel, ER. The pathway for oxygen: structure and function in the mammalian respiratory system. Cambridge, MA: Harvard University Press; 1984.

Weir, EK, Lopez-Barneo, J, Buckler, KJ, et al. Acute oxygen-sensing mechanisms. N Engl J Med. 2005;353:2042–2055.

Weir, EK, Cabrera, JA, Mahapatra, S, et al. The role of ion channels in hypoxic pulmonary vasoconstriction. Adv Exp Med Biol. 2010;661:3–14.

West, JB. Respiratory physiology—the essentials, ed 9. Baltimore: Lippincott Williams & Wilkins; 2012.