Guyton and Hall Textbook of Medical Physiology, 12th Ed


Pulmonary Circulation, Pulmonary Edema, Pleural Fluid

imageThe lung has two circulations: (1) A high-pressure, low-flow circulation supplies systemic arterial blood to the trachea, the bronchial tree including the terminal bronchioles, the supporting tissues of the lung, and the outer coats (adventia) of the pulmonary arteries and veins. The bronchial arteries, which are branches of the thoracic aorta, supply most of this systemic arterial blood at a pressure that is only slightly lower than the aortic pressure. (2) A low-pressure, high-flow circulation that supplies venous blood from all parts of the body to the alveolar capillaries where oxygen is added and carbon dioxide is removed. The pulmonary artery, which receives blood from the right ventricle, and its arterial branches carry blood to the alveolar capillaries for gas exchange and the pulmonary veins then return the blood to the left atrium to be pumped by the left ventricle though the systemic circulation.

In this chapter we discuss the special aspects of blood flow distribution and other hemodynamics of the pulmonary circulation that are especially important for gas exchange in the lungs.

Physiologic Anatomy of the Pulmonary Circulatory System

Pulmonary Vessels

The pulmonary artery extends only 5 centimeters beyond the apex of the right ventricle and then divides into right and left main branches that supply blood to the two respective lungs.

The pulmonary artery is thin, with a wall thickness one third that of the aorta. The pulmonary arterial branches are very short, and all the pulmonary arteries, even the smaller arteries and arterioles, have larger diameters than their counterpart systemic arteries. This, combined with the fact that the vessels are thin and distensible, gives the pulmonary arterial tree a large compliance, averaging almost 7 ml/mm Hg, which is similar to that of the entire systemic arterial tree. This large compliance allows the pulmonary arteries to accommodate the stroke volume output of the right ventricle.

The pulmonary veins, like the pulmonary arteries, are also short. They immediately empty their effluent blood into the left atrium.

Bronchial Vessels

Blood also flows to the lungs through small bronchial arteries that originate from the systemic circulation, amounting to about 1 to 2 percent of the total cardiac output. This bronchial arterial blood is oxygenated blood, in contrast to the partially deoxygenated blood in the pulmonary arteries. It supplies the supporting tissues of the lungs, including the connective tissue, septa, and large and small bronchi. After this bronchial and arterial blood has passed through the supporting tissues, it empties into the pulmonary veins and enters the left atrium, rather than passing back to the right atrium. Therefore, the flow into the left atrium and the left ventricular output are about 1 to 2 percent greater than that of the right ventricular output.


Lymph vessels are present in all the supportive tissues of the lung, beginning in the connective tissue spaces that surround the terminal bronchioles, coursing to the hilum of the lung, and then mainly into the right thoracic lymph duct. Particulate matter entering the alveoli is partly removed by way of these channels, and plasma protein leaking from the lung capillaries is also removed from the lung tissues, thereby helping to prevent pulmonary edema.

Pressures in the Pulmonary System

Pressure Pulse Curve in the Right Ventricle

The pressure pulse curves of the right ventricle and pulmonary artery are shown in the lower portion of Figure 38-1. These curves are contrasted with the much higher aortic pressure curve shown in the upper portion of the figure. The systolic pressure in the right ventricle of the normal human being averages about 25 mm Hg, and the diastolic pressure averages about 0 to 1 mm Hg, values that are only one-fifth those for the left ventricle.


Figure 38-1 Pressure pulse contours in the right ventricle, pulmonary artery, and aorta.

Pressures in the Pulmonary Artery

During systole, the pressure in the pulmonary artery is essentially equal to the pressure in the right ventricle, as also shown in Figure 38-1. However, after the pulmonary valve closes at the end of systole, the ventricular pressure falls precipitously, whereas the pulmonary arterial pressure falls more slowly as blood flows through the capillaries of the lungs.

As shown in Figure 38-2, the systolic pulmonary arterial pressure averages about 25 mm Hg in the normal human being, the diastolic pulmonary arterial pressure is about 8 mm Hg, and the mean pulmonary arterial pressure is 15 mm Hg.


Figure 38-2 Pressures in the different vessels of the lungs. D, diastolic; M, mean; S, systolic; red curve, arterial pulsations.

Pulmonary Capillary Pressure

The mean pulmonary capillary pressure, as diagrammed in Figure 38-2, is about 7 mm Hg. The importance of this low capillary pressure is discussed in detail later in the chapter in relation to fluid exchange functions of the pulmonary capillaries.

Left Atrial and Pulmonary Venous Pressures

The mean pressure in the left atrium and the major pulmonary veins averages about 2 mm Hg in the recumbent human being, varying from as low as 1 mm Hg to as high as 5 mm Hg. It usually is not feasible to measure a human being’s left atrial pressure using a direct measuring device because it is difficult to pass a catheter through the heart chambers into the left atrium. However, the left atrial pressure can often be estimated with moderate accuracy by measuring the so-called pulmonary wedge pressure. This is achieved by inserting a catheter first through a peripheral vein to the right atrium, then through the right side of the heart and through the pulmonary artery into one of the small branches of the pulmonary artery, finally pushing the catheter until it wedges tightly in the small branch.

The pressure measured through the catheter, called the “wedge pressure,” is about 5 mm Hg. Because all blood flow has been stopped in the small wedged artery, and because the blood vessels extending beyond this artery make a direct connection with the pulmonary capillaries, this wedge pressure is usually only 2 to 3 mm Hg greater than the left atrial pressure. When the left atrial pressure rises to high values, the pulmonary wedge pressure also rises. Therefore, wedge pressure measurements can be used to clinically study changes in pulmonary capillary pressure and left atrial pressure in patients with congestive heart failure.

Blood Volume of the Lungs

The blood volume of the lungs is about 450 milliliters, about 9 percent of the total blood volume of the entire circulatory system. Approximately 70 milliliters of this pulmonary blood volume is in the pulmonary capillaries, and the remainder is divided about equally between the pulmonary arteries and the veins.

The Lungs Serve as a Blood Reservoir

Under various physiological and pathological conditions, the quantity of blood in the lungs can vary from as little as one-half normal up to twice normal. For instance, when a person blows out air so hard that high pressure is built up in the lungs—such as when blowing a trumpet—as much as 250 milliliters of blood can be expelled from the pulmonary circulatory system into the systemic circulation. Also, loss of blood from the systemic circulation by hemorrhage can be partly compensated for by the automatic shift of blood from the lungs into the systemic vessels.

Cardiac Pathology May Shift Blood from the Systemic Circulation to the Pulmonary Circulation

Failure of the left side of the heart or increased resistance to blood flow through the mitral valve as a result of mitral stenosis or mitral regurgitation causes blood to dam up in the pulmonary circulation, sometimes increasing the pulmonary blood volume as much as 100 percent and causing large increases in the pulmonary vascular pressures. Because the volume of the systemic circulation is about nine times that of the pulmonary system, a shift of blood from one system to the other affects the pulmonary system greatly but usually has only mild systemic circulatory effects.

Blood Flow Through the Lungs and Its Distribution

The blood flow through the lungs is essentially equal to the cardiac output. Therefore, the factors that control cardiac output—mainly peripheral factors, as discussed in Chapter 20—also control pulmonary blood flow. Under most conditions, the pulmonary vessels act as passive, distensible tubes that enlarge with increasing pressure and narrow with decreasing pressure. For adequate aeration of the blood to occur, it is important for the blood to be distributed to those segments of the lungs where the alveoli are best oxygenated. This is achieved by the following mechanism.

Decreased Alveolar Oxygen Reduces Local Alveolar Blood Flow and Regulates Pulmonary Blood Flow Distribution

When the concentration of oxygen in the air of the alveoli decreases below normal, especially when it falls below 70 percent of normal (below 73 mm Hg Po2), the adjacent blood vessels constrict, with the vascular resistance increasing more than fivefold at extremely low oxygen levels. This is opposite to the effect observed in systemic vessels, which dilate rather than constrict in response to low oxygen. It is believed that the low oxygen concentration causes some yet undiscovered vasoconstrictor substance to be released from the lung tissue; this substance promotes constriction of the small arteries and arterioles. It has been suggested that this vasoconstrictor might be secreted by the alveolar epithelial cells when they become hypoxic.

This effect of low oxygen on pulmonary vascular resistance has an important function: to distribute blood flow where it is most effective. That is, if some alveoli are poorly ventilated so that their oxygen concentration becomes low, the local vessels constrict. This causes the blood to flow through other areas of the lungs that are better aerated, thus providing an automatic control system for distributing blood flow to the pulmonary areas in proportion to their alveolar oxygen pressures.

Effect of Hydrostatic Pressure Gradients in the Lungs on Regional Pulmonary Blood Flow

In Chapter 15, it was pointed out that the blood pressure in the foot of a standing person can be as much as 90 mm Hg greater than the pressure at the level of the heart. This is caused by hydrostatic pressure—that is, by the weight of the blood itself in the blood vessels. The same effect, but to a lesser degree, occurs in the lungs. In the normal, upright adult, the lowest point in the lungs is about 30 cm below the highest point. This represents a 23 mm Hg pressure difference, about 15 mm Hg of which is above the heart and 8 below. That is, the pulmonary arterial pressure in the uppermost portion of the lung of a standing person is about 15 mm Hg less than the pulmonary arterial pressure at the level of the heart, and the pressure in the lowest portion of the lungs is about 8 mm Hg greater. Such pressure differences have profound effects on blood flow through the different areas of the lungs. This is demonstrated by the lower curve in Figure 38-3, which depicts blood flow per unit of lung tissue at different levels of the lung in the upright person. Note that in the standing position at rest, there is little flow in the top of the lung but about five times as much flow in the bottom. To help explain these differences, one often describes the lung as being divided into three zones, as shown in Figure 38-4. In each zone, the patterns of blood flow are quite different.


Figure 38-3 Blood flow at different levels in the lung of an upright person at rest and during exercise. Note that when the person is at rest, the blood flow is very low at the top of the lungs; most of the flow is through the bottom of the lung.


Figure 38-4 Mechanics of blood flow in the three blood flow zones of the lung: zone 1, no flow—alveolar air pressure (PALV) is greater than arterial pressure; zone 2, intermittent flow—systolic arterial pressure rises higher than alveolar air pressure, but diastolic arterial pressure falls below alveolar air pressure; and zone 3, continuous flow—arterial pressure and pulmonary capillary pressure (Ppc) remain greater than alveolar air pressure at all times.

Zones 1, 2, and 3 of Pulmonary Blood Flow

The capillaries in the alveolar walls are distended by the blood pressure inside them, but simultaneously they are compressed by the alveolar air pressure on their outsides. Therefore, any time the lung alveolar air pressure becomes greater than the capillary blood pressure, the capillaries close and there is no blood flow. Under different normal and pathological lung conditions, one may find any one of three possible zones (patterns) of pulmonary blood flow, as follows:

Zone 1: No blood flow during all portions of the cardiac cycle because the local alveolar capillary pressure in that area of the lung never rises higher than the alveolar air pressure during any part of the cardiac cycle

Zone 2: Intermittent blood flow only during the peaks of pulmonary arterial pressure because the systolic pressure is then greater than the alveolar air pressure, but the diastolic pressure is less than the alveolar air pressure

Zone 3: Continuous blood flow because the alveolar capillary pressure remains greater than alveolar air pressure during the entire cardiac cycle

Normally, the lungs have only zones 2 and 3 blood flow—zone 2 (intermittent flow) in the apices and zone 3 (continuous flow) in all the lower areas. For example, when a person is in the upright position, the pulmonary arterial pressure at the lung apex is about 15 mm Hg less than the pressure at the level of the heart. Therefore, the apical systolic pressure is only 10 mm Hg (25 mm Hg at heart level minus 15 mm Hg hydrostatic pressure difference). This 10 mm Hg apical blood pressure is greater than the zero alveolar air pressure, so blood flows through the pulmonary apical capillaries during cardiac systole. Conversely, during diastole, the 8 mm Hg diastolic pressure at the level of the heart is not sufficient to push the blood up the 15 mm Hg hydrostatic pressure gradient required to cause diastolic capillary flow. Therefore, blood flow through the apical part of the lung is intermittent, with flow during systole but cessation of flow during diastole; this is called zone 2 blood flow. Zone 2 blood flow begins in the normal lungs about 10 cm above the midlevel of the heart and extends from there to the top of the lungs.

In the lower regions of the lungs, from about 10 cm above the level of the heart all the way to the bottom of the lungs, the pulmonary arterial pressure during both systole and diastole remains greater than the zero alveolar air pressure. Therefore, there is continuous flow through the alveolar capillaries, or zone 3 blood flow. Also, when a person is lying down, no part of the lung is more than a few centimeters above the level of the heart. In this case, blood flow in a normal person is entirely zone 3 blood flow, including the lung apices.

Zone 1 Blood Flow Occurs Only Under Abnormal Conditions

Zone 1 blood flow, which means no blood flow at any time during the cardiac cycle, occurs when either the pulmonary systolic arterial pressure is too low or the alveolar pressure is too high to allow flow. For instance, if an upright person is breathing against a positive air pressure so that the intra-alveolar air pressure is at least 10 mm Hg greater than normal but the pulmonary systolic blood pressure is normal, one would expect zone 1 blood flow—no blood flow—in the lung apices. Another instance in which zone 1 blood flow occurs is in an upright person whose pulmonary systolic arterial pressure is exceedingly low, as might occur after severe blood loss.

Effect of Exercise on Blood Flow Through the Different Parts of the Lungs

Referring again to Figure 38-3, one sees that the blood flow in all parts of the lung increases during exercise. The increase in flow in the top of the lung may be 700 to 800 percent, whereas the increase in the lower part of the lung may be no more than 200 to 300 percent. The reason for these differences is that the pulmonary vascular pressures rise enough during exercise to convert the lung apices from a zone 2 pattern into a zone 3 pattern of flow.

Increased Cardiac Output During Heavy Exercise Is Normally Accommodated by the Pulmonary Circulation Without Large Increases in Pulmonary Artery Pressure

During heavy exercise, blood flow through the lungs increases fourfold to sevenfold. This extra flow is accommodated in the lungs in three ways: (1) by increasing the number of open capillaries, sometimes as much as threefold; (2) by distending all the capillaries and increasing the rate of flow through each capillary more than twofold; and (3) by increasing the pulmonary arterial pressure. In the normal person, the first two changes decrease pulmonary vascular resistance so much that the pulmonary arterial pressure rises very little, even during maximum exercise; this effect is shown in Figure 38-5.


Figure 38-5 Effect on mean pulmonary arterial pressure caused by increasing the cardiac output during exercise.

The ability of the lungs to accommodate greatly increased blood flow during exercise without increasing the pulmonary arterial pressure conserves the energy of the right side of the heart. This ability also prevents a significant rise in pulmonary capillary pressure, thus also preventing the development of pulmonary edema.

Function of the Pulmonary Circulation When the Left Atrial Pressure Rises as a Result of Left-Sided Heart Failure

The left atrial pressure in a healthy person almost never rises above +6 mm Hg, even during the most strenuous exercise. These small changes in left atrial pressure have virtually no effect on pulmonary circulatory function because this merely expands the pulmonary venules and opens up more capillaries so that blood continues to flow with almost equal ease from the pulmonary arteries.

When the left side of the heart fails, however, blood begins to dam up in the left atrium. As a result, the left atrial pressure can rise on occasion from its normal value of 1 to 5 mm Hg all the way up to 40 to 50 mm Hg. The initial rise in atrial pressure, up to about 7 mm Hg, has very little effect on pulmonary circulatory function. But when the left atrial pressure rises to greater than 7 or 8 mm Hg, further increases in left atrial pressure above these levels cause almost equally great increases in pulmonary arterial pressure, thus causing a concomitant increased load on the right heart. Any increase in left atrial pressure above 7 or 8 mm Hg increases the capillary pressure almost equally as much. When the left atrial pressure has risen above 30 mm Hg, causing similar increases in capillary pressure, pulmonary edema is likely to develop, as we discuss later in the chapter.

Pulmonary Capillary Dynamics

Exchange of gases between the alveolar air and the pulmonary capillary blood is discussed in the next chapter. However, it is important for us to note here that the alveolar walls are lined with so many capillaries that, in most places, the capillaries almost touch one another side by side. Therefore, it is often said that the capillary blood flows in the alveolar walls as a “sheet of flow,” rather than in individual capillaries.

Pulmonary Capillary Pressure

No direct measurements of pulmonary capillary pressure have ever been made. However, “isogravimetric” measurement of pulmonary capillary pressure, using a technique described in Chapter 16, has given a value of 7 mm Hg. This is probably nearly correct because the mean left atrial pressure is about 2 mm Hg and the mean pulmonary arterial pressure is only 15 mm Hg, so the mean pulmonary capillary pressure must lie somewhere between these two values.

Length of Time Blood Stays in the Pulmonary Capillaries

From histological study of the total cross-sectional area of all the pulmonary capillaries, it can be calculated that when the cardiac output is normal, blood passes through the pulmonary capillaries in about 0.8 second. When the cardiac output increases, this can shorten to as little as 0.3 second. The shortening would be much greater were it not for the fact that additional capillaries, which normally are collapsed, open up to accommodate the increased blood flow. Thus, in only a fraction of a second, blood passing through the alveolar capillaries becomes oxygenated and loses its excess carbon dioxide.

Capillary Exchange of Fluid in the Lungs and Pulmonary Interstitial Fluid Dynamics

The dynamics of fluid exchange across the lung capillary membranes are qualitatively the same as for peripheral tissues. However, quantitatively, there are important differences, as follows:

1. The pulmonary capillary pressure is low, about 7 mm Hg, in comparison with a considerably higher functional capillary pressure in the peripheral tissues of about 17 mm Hg.

2. The interstitial fluid pressure in the lung is slightly more negative than that in the peripheral subcutaneous tissue. (This has been measured in two ways: by a micropipette inserted into the pulmonary interstitium, giving a value of about −5 mm Hg, and by measuring the absorption pressure of fluid from the alveoli, giving a value of about −8 mm Hg.)

3. The pulmonary capillaries are relatively leaky to protein molecules, so the colloid osmotic pressure of the pulmonary interstitial fluid is about 14 mm Hg, in comparison with less than half this value in the peripheral tissues.

4. The alveolar walls are extremely thin, and the alveolar epithelium covering the alveolar surfaces is so weak that it can be ruptured by any positive pressure in the interstitial spaces greater than alveolar air pressure (>0 mm Hg), which allows dumping of fluid from the interstitial spaces into the alveoli.

Now let us see how these quantitative differences affect pulmonary fluid dynamics.

Interrelations Between Interstitial Fluid Pressure and Other Pressures in the Lung

Figure 38-6 shows a pulmonary capillary, a pulmonary alveolus, and a lymphatic capillary draining the interstitial space between the blood capillary and the alveolus. Note the balance of forces at the blood capillary membrane, as follows:


Figure 38-6 Hydrostatic and osmotic forces in mm Hg at the capillary (left) and alveolar membrane (right) of the lungs. Also shown is the tip end of a lymphatic vessel (center) that pumps fluid from the pulmonary interstitial spaces.

(Modified from Guyton AC, Taylor AE, Granger HJ: Circulatory Physiology II: Dynamics and Control of the Body Fluids. Philadelphia: WB Saunders, 1975.)


mm Hg

Forces tending to cause movement of fluid outward from the capillaries and into the pulmonary interstitium:

Capillary pressure

Interstitial fluid colloid osmotic pressure

Negative interstitial fluid pressure



Forces tending to cause absorption of fluid into the capillaries:

Plasma colloid osmotic pressure



Thus, the normal outward forces are slightly greater than the inward forces, providing a mean filtration pressure at the pulmonary capillary membrane; this can be calculated as follows:


mm Hg

Total outward force

Total inward force



This filtration pressure causes a slight continual flow of fluid from the pulmonary capillaries into the interstitial spaces, and except for a small amount that evaporates in the alveoli, this fluid is pumped back to the circulation through the pulmonary lymphatic system.

Negative Pulmonary Interstitial Pressure and the Mechanism for Keeping the Alveoli “Dry.”

What keeps the alveoli from filling with fluid under normal conditions? One’s first inclination is to think that the alveolar epithelium is strong enough and continuous enough to keep fluid from leaking out of the interstitial spaces into the alveoli. This is not true because experiments have shown that there are always openings between the alveolar epithelial cells through which even large protein molecules, as well as water and electrolytes, can pass.

However, if one remembers that the pulmonary capillaries and the pulmonary lymphatic system normally maintain a slight negative pressure in the interstitial spaces, it is clear that whenever extra fluid appears in the alveoli, it will simply be sucked mechanically into the lung interstitium through the small openings between the alveolar epithelial cells. Then the excess fluid is either carried away through the pulmonary lymphatics or absorbed into the pulmonary capillaries. Thus, under normal conditions, the alveoli are kept “dry,” except for a small amount of fluid that seeps from the epithelium onto the lining surfaces of the alveoli to keep them moist.

Pulmonary Edema

Pulmonary edema occurs in the same way that edema occurs elsewhere in the body. Any factor that increases fluid filtration out of the pulmonary capillaries or that impedes pulmonary lymphatic function and causes the pulmonary interstitial fluid pressure to rise from the negative range into the positive range will cause rapid filling of the pulmonary interstitial spaces and alveoli with large amounts of free fluid.

The most common causes of pulmonary edema are as follows:

1. Left-sided heart failure or mitral valve disease, with consequent great increases in pulmonary venous pressure and pulmonary capillary pressure and flooding of the interstitial spaces and alveoli.

2. Damage to the pulmonary blood capillary membranes caused by infections such as pneumonia or by breathing noxious substances such as chlorine gas or sulfur dioxide gas. Each of these causes rapid leakage of both plasma proteins and fluid out of the capillaries and into both the lung interstitial spaces and the alveoli.

“Pulmonary Edema Safety Factor.”

Experiments in animals have shown that the pulmonary capillary pressure normally must rise to a value at least equal to the colloid osmotic pressure of the plasma inside the capillaries before significant pulmonary edema will occur. To give an example, Figure 38-7 shows how different levels of left atrial pressure increase the rate of pulmonary edema formation in dogs. Remember that every time the left atrial pressure rises to high values, the pulmonary capillary pressure rises to a level 1 to 2 mm Hg greater than the left atrial pressure. In these experiments, as soon as the left atrial pressure rose above 23 mm Hg (causing the pulmonary capillary pressure to rise above 25 mm Hg), fluid began to accumulate in the lungs. This fluid accumulation increased even more rapidly with further increases in capillary pressure. The plasma colloid osmotic pressure during these experiments was equal to this 25 mm Hg critical pressure level. Therefore, in the human being, whose normal plasma colloid osmotic pressure is 28 mm Hg, one can predict that the pulmonary capillary pressure must rise from the normal level of 7 mm Hg to more than 28 mm Hg to cause pulmonary edema, giving an acute safety factor against pulmonary edemaof 21 mm Hg.


Figure 38-7 Rate of fluid loss into the lung tissues when the left atrial pressure (and pulmonary capillary pressure) is increased.

(From Guyton AC, Lindsey AW: Effect of elevated left atrial pressure and decreased plasma protein concentration on the development of pulmonary edema. Circ Res 7:649, 1959.)

Safety Factor in Chronic Conditions

When the pulmonary capillary pressure remains elevated chronically (for at least 2 weeks), the lungs become even more resistant to pulmonary edema because the lymph vessels expand greatly, increasing their capability of carrying fluid away from the interstitial spaces perhaps as much as 10-fold. Therefore, in patients with chronic mitral stenosis, pulmonary capillary pressures of 40 to 45 mm Hg have been measured without the development of lethal pulmonary edema.

Rapidity of Death in Acute Pulmonary Edema

When the pulmonary capillary pressure rises even slightly above the safety factor level, lethal pulmonary edema can occur within hours, or even within 20 to 30 minutes if the capillary pressure rises 25 to 30 mm Hg above the safety factor level. Thus, in acute left-sided heart failure, in which the pulmonary capillary pressure occasionally does rise to 50 mm Hg, death frequently ensues in less than 30 minutes from acute pulmonary edema.

Fluid in the Pleural Cavity

When the lungs expand and contract during normal breathing, they slide back and forth within the pleural cavity. To facilitate this, a thin layer of mucoid fluid lies between the parietal and visceral pleurae.

Figure 38-8 shows the dynamics of fluid exchange in the pleural space. The pleural membrane is a porous, mesenchymal, serous membrane through which small amounts of interstitial fluid transude continually into the pleural space. These fluids carry with them tissue proteins, giving the pleural fluid a mucoid characteristic, which is what allows extremely easy slippage of the moving lungs.


Figure 38-8 Dynamics of fluid exchange in the intrapleural space.

The total amount of fluid in each pleural cavity is normally slight, only a few milliliters. Whenever the quantity becomes more than barely enough to begin flowing in the pleural cavity, the excess fluid is pumped away by lymphatic vessels opening directly from the pleural cavity into (1) the mediastinum, (2) the superior surface of the diaphragm, and (3) the lateral surfaces of the parietal pleura. Therefore, the pleural space—the space between the parietal and visceral pleurae—is called a potential space because it normally is so narrow that it is not obviously a physical space.

“Negative Pressure” in Pleural Fluid

A negative force is always required on the outside of the lungs to keep the lungs expanded. This is provided by negative pressure in the normal pleural space. The basic cause of this negative pressure is pumping of fluid from the space by the lymphatics (which is also the basis of the negative pressure found in most tissue spaces of the body). Because the normal collapse tendency of the lungs is about −4 mm Hg, the pleural fluid pressure must always be at least as negative as −4 mm Hg to keep the lungs expanded. Actual measurements have shown that the pressure is usually about −7 mm Hg, which is a few millimeters of mercury more negative than the collapse pressure of the lungs. Thus, the negativity of the pleural fluid keeps the normal lungs pulled against the parietal pleura of the chest cavity, except for an extremely thin layer of mucoid fluid that acts as a lubricant.

Pleural Effusion—Collection of Large Amounts of Free Fluid in the Pleural Space

Pleural effusion is analogous to edema fluid in the tissues and can be called “edema of the pleural cavity.” The causes of the effusion are the same as the causes of edema in other tissues (discussed in Chapter 25), including (1) blockage of lymphatic drainage from the pleural cavity; (2) cardiac failure, which causes excessively high peripheral and pulmonary capillary pressures, leading to excessive transudation of fluid into the pleural cavity; (3) greatly reduced plasma colloid osmotic pressure, thus allowing excessive transudation of fluid; and (4) infection or any other cause of inflammation of the surfaces of the pleural cavity, which breaks down the capillary membranes and allows rapid dumping of both plasma proteins and fluid into the cavity.


Bogaard H.J., Abe K., Vonk Noordegraaf A., et al. The right ventricle under pressure: cellular and molecular mechanisms of right-heart failure in pulmonary hypertension. Chest. 2009;135:794.

Effros R.M., Parker J.C. Pulmonary vascular heterogeneity and the Starling hypothesis. Microvasc Res. 78(71), 2009.

Effros R.M., Pornsuriyasak P., Porszasz J., et al. Indicator dilution measurements of extravascular lung water: basic assumptions and observations. Am J Physiol Lung Cell Mol Physiol. 2008;294:L1023.

Guyton A.C., Lindsey A.W. Effect of elevated left atrial pressure and decreased plasma protein concentration on the development of pulmonary edema. Circ Res. 1959;7:649.

Guyton A.C., Taylor A.E., Granger H.J. Circulatory Physiology. II. Dynamics and Control of the Body Fluids. Philadelphia: WB Saunders, 1975.

Hoschele S., Mairbaurl H. Alveolar flooding at high altitude: failure of reabsorption? News Physiol Sci. 2003;18:55.

Hughes M., West J.B. Gravity is the major factor determining the distribution of blood flow in the human lung. J Appl Physiol. 2008;104:1531.

Lai-Fook S.J. Pleural mechanics and fluid exchange. Physiol Rev. 2004;84:385.

Michelakis E.D., Wilkins M.R., Rabinovitch M. Emerging concepts and translational priorities in pulmonary arterial hypertension. Circulation. 2008;118:1486.

Miserocchi G., Negrini D., Passi A., et al. Development of lung edema: interstitial fluid dynamics and molecular structure. News Physiol Sci. 2001;16:66.

Parker J.C. Hydraulic conductance of lung endothelial phenotypes and Starling safety factors against edema. Am J Physiol Lung Cell Mol Physiol. 2007;292:L378.

Parker J.C., Townsley M.I. Physiological determinants of the pulmonary filtration coefficient. Am J Physiol Lung Cell Mol Physiol. 2008;295:L235.

Peinado V.I., Pizarro S., Barberà J.A. Pulmonary vascular involvement in COPD. Chest. 2008;134:808.

Robertson H.T., Hlastala M.P. Microsphere maps of regional blood flow and regional ventilation. J Appl Physiol. 2007;102:1265.

West J.B. Respiratory Physiology—The Essentials, ed 8. Baltimore: Lippincott, Williams & Wilkins, 2008.


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