Pleural Disease

In moving from the lung to other structures that are part of the process of respiration, we next consider the adjacent pleura. In clinical medicine, the pleura is important not only because diseases of the lung commonly cause secondary abnormalities in the pleura, but also because the pleura is a major site of disease in its own right. Not infrequently, pleural disease is a manifestation of a multisystem process that is inflammatory, immune, or malignant.

This chapter discusses the anatomy of the pleura, followed by a presentation of several physiologic principles of fluid formation and absorption by the pleura and a discussion of two types of abnormalities that affect the pleura: liquid in the pleural space (pleural effusion) and air in the pleural space (pneumothorax). A comprehensive treatment of all the disorders that affect the pleura is beyond the scope of this text. Rather, this chapter aims to cover the major categories and give the reader an understanding of how different factors interact in producing pleural disease. The primary malignancy of the pleura, mesothelioma, is discussed in Chapter 21, which deals with neoplastic disease of the thorax.

Anatomy

The term pleura refers to the thin lining layer on the outer surface of the lung (visceral pleura), the corresponding lining layer on the inner surface of the chest wall (parietal pleura), and the space between them (pleural space) (Fig. 15-1). Because the visceral and parietal pleural surfaces normally touch each other, the space between them is usually only a potential space. It contains a thin layer of serous fluid coating the apposing surfaces. When air or a larger amount of fluid accumulates in the pleural space, the visceral and parietal pleural surfaces are separated, and the space between the lung and the chest wall becomes more apparent.

Figure 15-1 Anatomic features of pleura. Pleural space is located between visceral and parietal pleural surfaces. Pleura lines surfaces of lung in contact with chest wall (costal pleura) and mediastinal and diaphragmatic borders (mediastinal and diaphragmatic pleura, respectively). (From Lowell JR: Pleural effusions: a comprehensive review, Baltimore, 1977, University Park Press, p 77.)

The pleura lines not only the surfaces of the lung in direct contact with the chest wall but also the diaphragmatic and mediastinal borders of the lung. These surfaces are called the diaphragmatic and mediastinal pleura, respectively (see Fig. 15-1). Visceral pleura also separates the lobes of the lung from each other; therefore, the major and minor fissures are defined by two apposing visceral pleural surfaces.

Each of the two pleural surfaces, visceral and parietal, is a thin membrane, the surface of which consists of specific lining cells called mesothelial cells. Beneath the mesothelial cell layer is a thin layer of connective tissue. Blood vessels and lymphatic vessels course throughout the connective tissue and are important in the dynamics of liquid formation and resorption in the pleural space. On the parietal but not the visceral pleural surface, openings called stomata are located between the mesothelial cells. Each stoma leads to lymphatic channels, allowing a passageway for liquid from the pleural space to the lymphatic system. Sensory nerve endings in the parietal and diaphragmatic pleura apparently are responsible for the characteristic “pleuritic chest pain” arising from the pleura.

Blood vessels supplying the parietal pleural surface originate from the systemic arterial circulation, primarily the intercostal arteries. Venous blood from the parietal pleura drains to the systemic venous system. The visceral pleura is also supplied primarily by systemic arteries, specifically branches of the bronchial arterial circulation. However, unlike the parietal pleura, the visceral pleura has venous drainage into the pulmonary venous system. Depending on their location, the lymphatic vessels that drain the pleural surfaces transport their fluid contents to different lymph nodes. Ultimately, any liquid transported by the lymphatic channels finds its way to the right lymphatic or thoracic ducts, which empty into the systemic venous circulation.

Physiology

The pleural space normally contains only a small quantity of liquid (≈10 mL), which lubricates the apposing surfaces of the visceral and parietal pleurae. According to the current concept of pleural fluid formation and resorption, formation of fluid is ongoing primarily from the parietal pleural surface, and fluid is resorbed through the stomata into the lymphatic channels of the parietal pleura (Fig. 15-2). The normal rates of formation and resorption of fluid, which must be equal if the quantity of fluid within the pleural space is not changing, are believed to be approximately 15 to 20 mL/day.

Figure 15-2 Schematic diagram of normal filtration and resorption of fluid in pleural space. Solid arrow shows filtration of fluid from parietal pleural microvessels into pleural space. Arrowhead indicates removal of fluid through stomata and into parietal pleural lymphatics. Dashed arrows indicate a minor role for filtration and resorption of fluid by visceral pleural microvessels. (Adapted from Pistolesi M, Miniati M, Giuntini C: Pleural liquid and solute exchange, Am Rev Respir Dis 140:825–847, 1989.)

The normally occurring liquid in the pleural space is an ultrafiltrate from the pleural capillaries. Several different forces either promote or oppose fluid filtration. The net movement of fluid from the pleural capillaries to the pleural space depends on the magnitude of these counterbalancing forces. The hydrostatic pressure in the capillary promotes movement of fluid out of the vessel and into the pericapillary space, whereas the colloid osmotic pressure (the osmotic pressure exerted by protein drawing in fluid) hinders movement of liquid out of the capillary. Likewise, hydrostatic and colloid osmotic pressures in the pericapillary space comprise the opposing forces that act on liquid within the pericapillary region.

The effect of these forces is summarized in the Starling equation, which describes the movement of fluid between vascular and extravascular compartments of any part of the body, not just the pleura:

where K = filtration coefficient (a function of the permeability of the pleural surface), P = hydrostatic pressure, COP = colloid osmotic pressure, σ = measure of capillary permeability to protein (called the reflection coefficient), and the subscripts c and is refer to the capillary and pericapillary interstitial space, respectively. In this case, the pericapillary interstitial space is essentially the pleural space; therefore, P_is and COP_is refer to intrapleural pressure and the colloid osmotic pressure of pleural fluid, respectively. The intrapleural pressure—that is, the hydrostatic pressure within the pleural space—is negative, reflecting the outward elastic recoil of the chest wall and the inward elastic recoil of the lung.

When values obtained by direct measurement or by estimation are put into the Starling equation, a net pressure of approximately 9 cm H₂O favors movement of fluid from the parietal pleura to the pleural space. The critical factor responsible for the forces favoring formation of pleural fluid is the difference between the positive hydrostatic pressure in the pleural capillaries and the negative hydrostatic pressure within the pleural space.

The Starling equation can be applied to the parietal pleura:

P_c = 30 cm H₂O

P_is (mean intrapleural pressure) = − 5 cm H₂O

COP_c = 32 cm H₂O

COP_is = 6 cm H₂O

σ = 1, K = 1

Applying the same equation to fluid filtration from the visceral pleura is more difficult. The visceral pleural capillaries are supplied mainly by the systemic arterial circulation but are drained into the pulmonary venous circulation rather than the systemic venous circulation. Although currently unknown, the hydrostatic pressure in the visceral pleural capillaries is estimated to be less than in the parietal pleural capillaries. As a result, the driving pressure for formation of pleural fluid is normally greater at the parietal than at the visceral pleural surface, and most of the small amount of normal pleural fluid is thought to originate from filtration through the systemic capillaries of the parietal pleura.

Fluid movement at parietal pleura = [30 − (−5)] − 1(32 − 6) = 9 cm H₂O

Resorption of pleural fluid, including protein and cells in the fluid, occurs through the stomata between mesothelial cells on the parietal pleural surface. The fluid enters lymphatic channels, and valves within these channels ensure unidirectional flow. Movement of fluid through the valved lymphatics is believed to be aided by respiratory motion. When pleural fluid formation is increased, as occurs in many of the pathologic states to be discussed, the parietal pleural lymphatics are capable of increasing their flow substantially to accommodate at least some of the excess fluid formed.

Pleural fluid is filtered from the parietal pleura into the pleural space and reabsorbed through stomata into the parietal pleural lymphatics.

Pleural Effusion

In the normal individual, resorption of pleural fluid maintains pace with pleural fluid formation, so fluid does not accumulate. However, a variety of diseases affect the forces governing pleural fluid filtration and resorption, resulting in fluid formation exceeding fluid removal—that is, development of pleural effusion. The pathogenesis (dynamics) of fluid accumulation is discussed first, followed by a consideration of some of the etiologic factors, clinical features, and diagnostic approaches to pleural effusions.

Pathogenesis of Pleural Fluid Accumulation

In theory, a change in magnitude of any of the factors in the Starling equation can cause sufficient imbalance of pleural fluid dynamics to result in pleural fluid accumulation. In practice, it is easiest to divide these changes into two categories: (1) alteration of the permeability of the pleural surface (i.e., changes in the filtration coefficient [K] and reflection coefficient [σ] such that the pleura is more permeable to fluid and larger-molecular-weight components of blood, including proteins) and (2) alteration in the driving pressure, encompassing a change in hydrostatic or colloid osmotic pressures of the parietal or visceral pleura, without any change in pleural permeability.

The most common types of disease causing a change in the filtration and reflection coefficients are inflammatory or neoplastic diseases involving the pleura. In these circumstances, the pleural surface becomes more permeable to proteins, so the accumulated fluid has a relatively high protein content. This type of fluid, because of a change in permeability and its association with a relatively high protein content, is termed an exudate.

Increased permeability of the pleural surface is associated with exudative pleural fluid. Changes in pleural hydrostatic or colloid osmotic pressures are associated with transudative pleural fluid.

In contrast, an increase in hydrostatic pressure within pleural capillaries (as might be seen with high pulmonary venous pressure from congestive heart failure) or a decrease in plasma colloid osmotic pressure (as in hypoproteinemia) results in accumulation of fluid with a low protein content because the pleural barrier is still relatively impermeable to the movement of proteins. This type of fluid, because of a change in the driving pressure (without increased permeability) and the presence of a low protein content, is termed a transudate.

Another general mechanism accounting for some pleural effusions reflects neither altered permeability nor altered driving pressure. Rather, the fluid originates in the peritoneum as ascitic fluid and travels to the pleural space primarily via small diaphragmatic defects and perhaps also by diaphragmatic lymphatics. Considering that intrapleural pressure is more negative than intraperitoneal pressure, it is not surprising that fluid moves from the peritoneum to the pleural space when such defects exist.

Interference with the resorptive process for pleural fluid can contribute to development of effusions. This is seen primarily with blockage of the lymphatic drainage from the pleural space, as may occur when tumor cells invade the lymphatic channels or draining lymph nodes.

Etiology of Pleural Effusion

The numerous causes of pleural fluid accumulation are best divided into transudative and exudative categories (Table 15-1). This distinction is generally easy to make and is most important in guiding the physician along the best route for further evaluation. Transudative fluid usually implies that the pathologic process does not primarily involve the pleural surfaces, whereas exudative fluid often suggests that the pleura is affected by the disease process causing the effusion.

Table 15-1

MAJOR CAUSES OF PLEURAL EFFUSION

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