8: Anatomic and physiologic aspects of the pulmonary parenchyma
OUTLINE
Anatomy, 119
Physiology, 121
Chapters 8 through 11 focus on the region of the lung directly involved in gas exchange, often called the pulmonary parenchyma. This region includes the alveolar walls and spaces (with the alveolar-capillary interface) at the level of the alveolar sacs, ducts, and respiratory bronchioles. Although the broad group of disorders involving these structures traditionally has been described under the category of interstitial lung disease, the term diffuse parenchymal lung disease is increasingly used and more accurately reflects the breadth of the pathologic involvement.
This chapter provides a description of the normal anatomy of the gas-exchanging region of the lung and some aspects of its normal physiology. Chapter 9 provides an overview of the diffuse parenchymal lung diseases, emphasizing how disturbances in alveolar structure are closely linked with aberrations in function. Chapters 10 and 11 focus on specific disorders, mostly subacute or chronic, in which the main pathologic features reside within the alveolar wall. Pneumonia, acute lung injury (acute respiratory distress syndrome), and diseases of the pulmonary vasculature are deliberately excluded because of their different pathologic appearance and are considered separately in other parts of this text.
Although a wide variety of disorders affect the alveolar wall, many of the pathophysiologic features are common to many individual diseases. Knowledge of these common pathophysiologic features and their effects on the normal function of the lung is useful for understanding the consequences of individual disease entities. For specific diseases with special characteristics, a consideration of these individual features is included.
Anatomy
For the lung to function efficiently as a gas-exchanging organ, a large surface area must be available where O2 can be taken up and CO2 released. At the alveolar wall, where gas exchange occurs, an extensive network of capillaries coursing through and coming into close contact with alveolar gas facilitates the exchange. In the normal lung, the alveolar septa are extremely thin and delicate, with the capillaries closely apposed to the alveolar lumen, and there is little tissue extraneous to the gasexchanging process (Fig. 8.1).
FIGURE 8.1 Photomicrograph of alveolar walls shows a normal thin, lacy
appearance. At top of photo is bronchial lumen, lined by bronchial epithelial cells
(arrow). Peribronchial tissue lies between bronchial epithelium and alveolar walls.
Source: (Courtesy Dr. Earl Kasdon.)
The surface of the alveolar walls (the region bordering the alveolar lumen) is lined by a continuous layer of epithelial cells. Two different types of these lining epithelial cells, called type I and type II cells, can be identified. Type I cells are less numerous than type II cells but account for a much larger surface area. They have strikingly long and delicate cytoplasmic extensions that line more than 95% of the alveolar surface (Fig. 8.2). Type I cells function as a barrier preventing free movement of material, such as fluid, from the alveolar wall into the alveolar lumen. Although they have few cytoplasmic organelles, evidence indicates that type I cells play an important role in the regulation of ion and fluid balance in the lung, in part because they cover such a large part of the alveolar surface area.
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FIGURE 8.2 Schematic diagram of normal alveolar structure. Type I and type II
epithelial cells line alveolar wall. Type I cells are relatively flat and characterized
by long cytoplasmic processes. Type II cells are cuboidal. Two capillaries are
shown. A, alveolar space; C, capillary endothelial cells; IS, interstitial space
(relatively acellular region of the alveolar wall); L, type II cell cytoplasmic
lamellar bodies (source of surfactant); RBC, erythrocytes in capillary lumen.
Type I alveolar epithelial cells have long cytoplasmic processes that line almost the entire alveolar surface.
The second lining epithelial cell is the type II cell. Type II cells have three well-defined functions: synthesis of surfactant, alveolar epithelial repair, and ion and fluid transport. In contrast to type I cells, type II epithelial cells have a cuboidal shape and often bulge into the alveolar lumen. Type II cells are more numerous, but because they do not have long cytoplasmic extensions, they cover less than 5% of the alveolar surface. Type II cells have many cytoplasmic organelles (mitochondria, rough endoplasmic reticulum, Golgi apparatus), which relate to their important synthetic role.
Type II cells produce surfactant, are important in the reparative process for type I cells, and are active in ion and fluid transport.
The primary product of the type II cells is surfactant. Specific inclusion bodies within the type II cells, termed lamellar inclusions, contain the packaged form of surfactant that eventually is released into the alveolar lumen. Surfactant is a complex of molecules composed of a high proportion of lipids, associated proteins, and carbohydrates, all of which are necessary for effective function. Surfactant reduces the
surface tension of the alveoli. It stabilizes the alveolus in the same way a bubble is prevented from collapsing by a detergent material, thereby preventing microatelectasis (alveolar collapse on a microscopic level). During fetal development, surfactant is not synthesized until the third trimester. Defective or insufficient surfactant synthesis in premature infants may result in infant respiratory distress syndrome, and exogenous surfactant replacement therapy given shortly after birth improves outcomes.
Four types of protein are associated with surfactant: surfactant proteins A, B, C, and D (SP-A, SP-B, SP-C, and SP-D, respectively). The function of surfactant in maintaining a low surface tension is critically dependent on the hydrophobic proteins SP-B and SP-C. Although SP-A and SP-D also affect surface tension, they additionally have an important role in the innate immunity of the lung by opsonizing as well as directly inhibiting the growth of some microbial pathogens (see Chapter 22).
Type II cells have a significant role in maintenance and repair of the injured alveolar epithelium. Type I epithelial cells are quite susceptible to injury, whether from an external source via the airways or an internal source via the bloodstream. When type I cells are damaged, the reparative process involves hyperplasia of the type II cells and eventual differentiation into cells with the characteristics of type I cells. Normally, this orderly process results in some hyperplastic type II cells undergoing apoptosis, whereas the remainder transdifferentiate into thin, delicate, type I cells. As discussed in Chapter 11, defects in this process have been identified in idiopathic pulmonary fibrosis, a disease of progressive parenchymal scarring.
The third function of type II cells is regulation of alveolar fluid via transepithelial sodium and chloride transport. Proper regulation of ion and fluid balance requires an intact epithelium. Inhibition of this function occurs during inflammation and probably contributes to the edema formation seen in acute lung injury (see Chapter 29).
Type II cells are also involved in the synthesis of a number of other proteins. They have been reported to elaborate several growth factors and cytokines, cytokine receptors, and proteins involved in innate immunity, such as β-defensins. These additional activities of type II cells are areas of active research.
Pulmonary capillaries course through the alveolar walls as part of an extensive network of intercommunicating vessels. Unlike the alveolar epithelial cells, which are quite impermeable under normal circumstances, junctions between capillary endothelial cells permit passage of small-molecular- weight proteins. The importance of the permeability features of the alveolar epithelial and capillary endothelial cells will become apparent in the discussion of acute respiratory distress syndrome in Chapter 29, because this disorder is characterized by increased permeability and leakage of fluid and protein into alveolar spaces.
The alveolar epithelial and capillary endothelial cells rest on a basement membrane. At some regions of the alveolar wall, nothing stands between the epithelial and endothelial cells other than the basement membranes, which are fused to form a single structure. At other regions, the interstitial space, which consists of relatively acellular material (see Fig. 8.2), intervenes. The major components of the interstitial space are collagen, elastin, proteoglycans, a variety of macromolecules involved with cell-cell and cellmatrix interactions, some nerve endings, and some fibroblast-like cells. There are also small numbers of lymphocytes as well as cells that appear to be in a transition state between blood monocytes and alveolar macrophages (which are derived from circulating monocytes).
Within the alveolar lumen, a thin layer of liquid covers the alveolar epithelial cells. This extracellular alveolar lining layer is composed of an aqueous phase immediately adjacent to the epithelial cells, covered by a surface layer of lipid-rich surfactant produced by the type II epithelial cells. The alveolar lining layer also contains alveolar macrophages, phagocytic cells that are important in protecting the distal lung against bacteria and in clearing inhaled particulate matter. Alveolar macrophages and the innate immunity of the lung are discussed further in Chapter 22.
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