RESPIRATORY SURFACES


Thin-walled respiratory surfaces (alveoli) are distributed as isolated patches within the walls of respiratory bronchi, and as tube-like alveolar ducts and balloon-like alveolar sacs which contain groups of adjacent alveoli (Fig. 62.3).


ALVEOLAR AREA

Normal adult human alveoli have a mean total surface area of 143 m2: an adult respiratory system contains c.300 million alveoli. Their inflated diameter (c.250 μm) varies with lung position, and is greater in the upper regions than in the lower, because of the increased gravitational pressure at the lung base. These values vary considerably between normal young individuals, and the differences become even more marked with age as a result of degenerative changes.


ALVEOLAR STRUCTURE (Figs 62.1, 62.6, 62.7, 62.8, 62.9)

The alveoli are thin-walled pouches which provide the respiratory surface for gaseous exchange. Their walls contain two types of epithelial cell (pneumocytes), which cover a delicate connective tissue within which a network of capillaries ramify. Since the walls are extremely thin, they present a minimal barrier to gaseous exchange between the atmosphere and the blood in the capillaries. Adjacent alveoli are frequently in close contact and then the intervening connective tissue forms the central part of an interalveolar septum. Alveolar macrophages are present within the alveolar lumen, and migrate over the epithelial surface.
Interalveolar septum
The alveolar lining epithelium varies in thickness, but extensive areas of it are as little as 0.05 μm thick (see below). The epithelium lies on a basal lamina, which, in the thin portions of a septum, is fused with the basal lamina surrounding the adjacent capillaries. The total barrier to diffusion between air and blood in these thin portions may be as little as 0.2 μm. The thick portions of a septum contain connective tissue elements, including elastic fibres, collagen type III fibres, resident and migratory cells (Fig. 62.6).
Alveolar epithelial cells (pneumocytes)
The alveolar epithelium is a mosaic of Types I and II pneumocytes. Type I pneumocytes form over 90% of the alveolar area and share a fused basal lamina with that of the adjacent capillary endothelium to form the thin portions of interalveolar septa. They are simple squamous epithelial cells with a thin cytoplasm (0.05-0.2 μm) which extends from a thicker perinuclear region, and facilitates gaseous diffusion between the lumen of the alveolus and its capillaries. The edges of adjacent cells overlap, and they are joined by tight junctions which create a strict diffusion barrier between the alveolar surface and underlying tissues. Together with a similar endothelial barrier, this arrangement limits the movement of fluid from blood and interstitial spaces into the alveolar lumen (the blood-air barrier). If damaged, type I cells, which do not divide, are replaced by the proliferation of type II cells which are able to differentiate into type I pneumocytes.
The smaller type II cells are often more numerous than type I cells, but they contribute less than 10% of the surface area. They are rounded cells which protrude from the alveolar surface, particularly at the angles between alveolar profiles. In the human lung they are often associated with interalveolar pores of Köhn. Their cytoplasm contains numerous characteristic secretory lamellar bodies (Fig. 62.9), which they can recycle. Ultrastructurally, the lamellar bodies are comprised of concentric whorls of phospholipid-rich membrane, the precursors of alveolar surfactant.
Interalveolar pores (of Köhn)
These are small pores lined by epithelium (usually type II alveolar cells), which cross interalveolar septa to link adjacent alveolar air spaces. Humans have up to seven pores per alveolus, ranging in size from 2 to 13 μm. These small passages may sustain the flow of air, in the event of blockage of one of the alveolar ducts. They are also routes of migration for alveolar macrophages.
Alveolar macrophages
The respiratory portion of the lung and its cell types.
    Figure 62.6 The respiratory portion of the lung and its cell types.
Like macrophages in other sites in the body (p. 80), alveolar macrophages are derived from circulating monocyte precursors. They originate in haemopoietic tissue in the bone marrow, migrate into the alveolar lumen from adjacent blood vessels and connective tissue, and wander about on the epithelial surfaces. Alveolar macrophages clear the respiratory spaces of inhaled particles which are small enough to reach the alveoli, hence their alternative name of dust cells. Most of them migrate with their phagocytosed load to the bronchioles where they are swept into the mucociliary rejection current and removed from the lung. Others migrate through the epithelium of the alveoli into the lymphatics which drain the lung connective tissue, and thence into lymphoid tissue around the pulmonary lobules. Under normal conditions these cells have a granular cytoplasm because they contain phagocytosed particles: in smokers the latter have a characteristic appearance, and are called tar bodies.
Alveolar macrophages can be recovered from sputum, and are of diagnostic importance if they appear abnormal, for instance, whenever erythrocytes leak from pulmonary capillaries, macrophages which engulf red cells become brick red, and are detectable in 'rusty' sputum. They are typical of congestive heart failure, and therefore often termed heart-failure cells. Macrophages which have migrated back into the connective tissue of the lung settle in patches which are visible beneath the visceral pleura, e.g. carbon-filled cells give the lungs a mottled appearance. However, if the inhaled particles are abrasive or chemically active, they may elude macrophage removal, and instead damage the respiratory surface, which produces fibrosis and a concomitant reduction in the respiratory area. This occurs in many industrial diseases, e.g. pneumoconiosis, which is due to coal dust, or asbestosis, where the long thin fibres of asbestos can cause considerable damage and may trigger fatal mesothelioma in the pleural lining. When actively phagocytic, macrophages release proteases: if antiproteases (e.g. α1 antitrypsin), which are normally present in the alveolar lining, are deficient, then macrophage activity may damage the lung. Alveolar macrophages are also involved in the turnover of surfactant.
In pathological conditions other cells, e.g. neutrophil leukocytes and lymphocytes, may enter the alveoli and other parts of the respiratory tree, and their presence imparts a characteristic yellow appearance to the sputum.
 Electron micrograph showing the alveolar septum between three adjacent alveoli
 
    Figure 62.7 Electron micrograph showing the alveolar septum between three adjacent alveoli (A). The septum contains two capillaries (C1 and C2) in section; the lower one is cut obliquely through the nucleus of one of its endothelial lining cells and its lumen in three places. Type I pneumocytes (P1) line the alveolar air spaces except where a type II pneumocyte ((P2) bottom centre), with cytoplasmic lamellar bodies, is located. (By permission from Young B, Heath JW 2000 Wheater's Functional Histology. Edinburgh: Churchill Livingstone.)


ALVEOLAR SURFACTANT

The alveolar surface is normally covered by a film of pulmonary surfactant, which is a complex mixture, mainly of phospholipids (particularly dipalmitoylphosphatidylcholine and phosphatidylglycerol), with some protein and neutral lipid (Devendra & Spragg 2002). Surfactant is stored in lamellar bodies and secreted in the form of tubular myelin (unrelated to myelin of the nervous system) by type II pneumocytes. It is recycled by type II pneumocytes, or cleared (phagocytosed) by alveolar macrophages. Clara cells of the bronchiolar epithelium are believed to secrete surfactant of a different composition.
 Electron micrograph of the thin portion of an interalveolar septum.
    Figure 62.8 Electron micrograph of the thin portion of an interalveolar septum. Part of an erythrocyte (Er) is shown in the capillary lumen (bottom), which is lined by endothelium (E). The alveolar air space (top) is lined by a type I pneumocyte (P1). Between the attenuated cytoplasm of the two cells is a shared basal lamina (BL). (By permission from Young B, Heath JW 2000 Wheater's Functional Histology. Edinburgh: Churchill Livingstone.)
  Electron micrograph of cytoplasmic lamellar bodies in a Type II pneumocyte
    Figure 62.9 Electron micrograph of cytoplasmic lamellar bodies in a Type II pneumocyte. They are composed mainly of phospholipids which are released by exocytosis and contribute to the surfactant secreted by these pneumocytes and Clara cells of the respiratory bronchioles. (By permission from Young B, Heath JW 2000 Wheater's Functional Histology. Edinburgh: Churchill Livingstone.)
Surface tension at the alveolar surface is very high, because the alveoli are minute. This opposes expansion during inspiration, and tends to collapse the alveoli in expiration. The detergent-like properties of pulmonary surfactant greatly reduce the surface tension, and make ventilation of the alveoli much more efficient.


REFERENCES

Devendra G, Spragg RG 2002 Lung surfactant in subacute pulmonary disease. Respir Res 3: 19-22. Medline Similar articles Full article
Jeffrey PK 2003 Microscopic structure of the lung. In: Gibson GJ, Geddes DM, Costabel V, Stok PJ, Corrin B (eds), Respiratory Medicine, 3rd edn. London: Elsevier Science: 34-50.