The olfactory epithelium contains three major types of cells (Figures 13-2 and 13-3): (1) basal cells, (2) olfactory cells (bipolar neurons), and (3) supporting or sustentacular cells.

Figure 13-2 Olfactory mucosa

Figure 13-3 Olfactory epithelium

The basal cells are mitotically active stem cells, producing daughter cells that differentiate first into immature olfactory cells and then into mature olfactory cells. Olfactory cells proliferate during adult life. The life span of an olfactory cell is about 30 to 60 days.

The olfactory cell is highly polarized (see Figure 13-3). The apical region, facing the surface of the mucosa, forms a knoblike ending (called olfactory vesicle or olfactory knob) with 10 to 20 modified cilia. The basal region gives rise to an axon. Several axons, projecting from the olfactory cells, form small unmyelinated bundles (called olfactory fila; from Latin filum, thread) surounded by glial-like cells. Nerve bundles cross the cribriform plate of the ethmoid bone and contact in the glomerulus dendrites of mitral cells, neurons of the olfactory bulb, to establish appropriate synaptic connections (see Box 13-A).

Box 13-A Olfactory epithelium

• The olfactory epithelium consists of olfactory cells (bipolar neurons), basal cells (a stem cell that differentiates into olfactory cells), and sustentacular or supporting cells. These cells can be identifed on the basis of the position and shape of their nuclei (see Figure 13-3).

• An olfactory cell has two portions: an apical dendrite with a knob bearing about 10 to 20 olfactory nonmotile modified cilia and a basal axon, forming bundles that will pass through the cribriform plate of the ethmoid bone.

• Cilia contain the odorant receptor (OR). There are about 1000 genes expressing ORs, but each olfactory receptor cell expresses only one OR gene.

• Secretions of the serous glands of Bowman contain odorant-binding protein.

• Axons from olfactory cells with the same OR terminate in one to three glomeruli present in the olfactory bulb. Dendritic endings of predominantly mitral cells extend into the glomeruli. Axons of mitral cells form the olfactory tract.

• Olfactory receptor cells have a life span of 30 to 60 days and can regenerate from basal cells.

• Temporary or permanent damage to the olfactory epithelium causes anosmia (Greek an, not; osme, sense of smell).

Olfactory serous glands (called glands of Bowman), which are present under the epithelium, secrete a serous fluid in which odoriferous substances are dissolved. The secretory fluid contains the odorant-binding protein (OBP) with high binding affinity for a large number of odorant molecules. OBP carries odorants to receptors present on the surface of the modified cilia and removes them after they have been sensed. In addition, the secretory product of the glands of Bowman contains protective substances such as lysozyme and immunoglobulin A (IgA) secreted by plasma cells.

LARYNX

The two main functions of the larynx are (1) to produce sound and (2) to close the trachea during swallowing to prevent food and saliva from entering the airway.

The wall of the larynx is made up of the thyroid and cricoid hyaline cartilage and the elastic cartilage core of the epiglottis extending over the lumen (Figure 13-4).

Figure 13-4 Structure of the larynx

Extrinsic laryngeal muscles attach the larynx to the hyoid bone to raise the larynx during swallowing.

Intrinsic laryngeal muscles (abductor, adductors, and tensors), innervated by the recurrent laryngeal nerve, link the thyroid and cricoid cartilages. When intrinsic muscles contract, the tension on the vocal cords changes to modulate phonation. The middle and lower laryngeal arteries (derived from the superior and inferior thyroid artery) supply the larynx. Lymphatic plexuses drain to the upper cervical lymph nodes and to the nodes along the trachea.

The larynx can be subdivided into three regions:

1. The supraglottis, which includes the epiglottis, false vocal cords (or folds), and laryngeal ventricles.

2. The glottis, consisting of the true vocal cords (or folds) and the anterior and posterior commissures.

3. The subglottis, the region below the true vocal cords, extending down to the lower border of the cricoid cartilage.

During forced inspiration, vocal cords are abducted, and the space between the vocal cords widens.

During phonation, the vocal cords are adducted and the space between the vocal cords changes into a linear slit. The vibration of the free edges of the cords (a cover consisting of both the stratified squamous epithelial covering and the superficial layer of the lamina propria, known as Reinke’s space) during passage of air between them produces sound. The contraction of the intrinsic muscles of the larynx, forming the body of the cords, increases tension on the vocal cords, changing the pitch of the produced sound (see Box 13-B).

Box 13-B True vocal cords or folds

• The true vocal cords or folds consist of two regions—the cover and the core—with different structural properties.

• The cover consists of stratified squamous epithelium and the superficial layer of the lamina propria (the space of Reinke). The core is composed of the intermediate and deep layers of the lamina propria (representing the vocal ligament) and the vocalis or thyroarytenoid muscle.

The cover is flexible, whereas the core is stiff and has contractile properties allowing adjustment of stiffness.

• During phonation, the cover of the vocal cords displays horizontal movements and vertical undulation (known as mucosal wave). Changes in the stiffness in the core of the cords modify the mucosal wave. As the stiffness of the cord increases, the velocity of the mucosal wave increases and the pitch rises.

The mucosa of the larynx is continuous with that of the pharynx and the trachea. A stratified squamous epithelium covers the lingual surface and a small extension of the pharyngeal surface of the epiglottis and the true vocal cords. Elsewhere, the epithelium is pseudostratified ciliated, with goblet cells.

Laryngeal seromucous glands are found throughout the lamina propria, except at the level of the true vocal cords. The lamina propria of the true vocal cords consists of three layers (see Figure 13-4): (1) a superficial layer containing extracellular matrix and few elastic fibers. This layer is known as Reinke’s space; (2) an intermediate layer with an increased content of elastic fibers; and (3) a deep layer with abundant elastic and collagen fibers.

Reinke’s space and the epithelial covering are responsible for vocal cord vibration. Reinke’s edema results when viral infection, trauma (laryngeal endoscopy), or severe coughing spells cause fluid to accumulate in the superficial layer of the lamina propria. Both the intermediate and deep layer of the lamina propria constitute the vocal ligament.

The lamina propria is usually rich in mast cells. Mast cells participate in hypersensitivity reactions leading to edema and laryngeal obstruction, a potential medical emergency. Croup designates a laryngotracheobronchitis in children, in which an inflammatory process narrows the airway and produces inspiratory stridor.

TRACHEA

The trachea, the major segment of the conducting region of the respiratory system, is the continuation of the larynx.

The trachea branches to form the right and left primary bronchi entering the hilum of each lung. The hilum is the region where the primary bronchus, pulmonary artery, pulmonary vein, nerves, and lymphatics enter and leave the lung. Secondary divisions of the bronchi and accompanying connective tissue septa divide each lung into lobes.

The right lung has three lobes, whereas the left lung has two lobes.

Subsequent bronchial divisions further subdivide each lobe into bronchopulmonary segments. The bronchopulmonary segment is the gross anatomic unit of the lung that can be removed surgically. Successive bronchial branching gives rise to several generations of bronchopulmonary subsegments.

The trachea and main bronchi are lined by pseudostratified columnar ciliated epithelium resting on a distinct basal lamina. Several types of cells can be identified (Figure 13-5):

1. Columnar ciliated cells are the predominant cell population, extending from the lumen to the basal lamina.

2. Goblet cells are abundant nonciliated cells, also in contact with the lumen and the basal lamina. They produce mucin polymers MUC5AC and MUC5B (see Figure 13-5).

3. Basal cells rest on the basal lamina but do not extend to the lumen.

4. Cells of Kulchitsky are neuroendocrine cells also resting on the basal lamina and are predominantly found at the bifurcation of lobar bronchi. They give rise to bronchial carcinoid tumors within the bronchial mucosa. These cells secrete peptide hormones such as serotonin, calcitonin, antidiuretic hormone (ADH), and adrenocorticotropic hormone (ACTH).

Figure 13-5 Structure of the trachea

The lamina propria contains elastic fibers. The submucosa displays mucous and serous glands that, together with goblet cells, produce components of the airways mucus (see Box 13-C).

Box 13-C Airway mucus

• Airway mucus traps inhaled particles and transports them out of the lungs by ciliary beating and cough. Excessive mucus or deficient clearance are characteristics of all common airway diseases.

• Airway mucus is produced by three secretory cell types: (1) Goblet cells; (2) Clara cells of the terminal bronchioles; and (3) serous cells of the submucosal glands.

• Mucus contains: (1) Mucins MUC5AC and MUC5B; (2) antimicrobial molecules (defensins, lysozyme, and immunoglobulin A); (3) immunomodulatory molecules (secretoglobin and cytokines); and (4) protective molecules (trefoil proteins and heregulin.

• Normal airway mucus is 97% water and 3% solids (mucins, non-mucin proteins, salts, lipids, and cellular debris). The hydration of the mucus determines its viscosity and elastic properties, two essential characteristics for normal clearance of mucus by ciliary action and cough.

• Airway mucus consists of two layers: (1) A periciliary layer; and (2) a mucus gel layer atop the periciliary layer. Polymeric MUC5AC and MUC5B are continuously synthesized and secreted to replenish the mucus gel layer cleared by ciliary beating to eliminate inhaled particles, pathogens, and dissolved chemicals that might damage the lungs.

The framework of the trachea and extrapulmonary bronchi consists of a stack of C-shaped hyaline cartilages, each surrounded by a fibroelastic layer blending with the perichondrium. In the trachea and primary bronchi, the open ends of the cartilage rings point posteriorly to the esophagus. The lowest tracheal cartilage is the carinal cartilage. Transverse fibers of the trachealis muscle attach to the inner ends of the cartilage. In branching bronchi, cartilage rings (see Figure 13-5) are replaced by irregularly shaped cartilage plates (Figure 13-6), surrounded by smooth muscle bundles in a spiral arrangement.

Figure 13-6 Segmentation of the intrapulmonary bronchial tree

INTRAPULMONARY SEGMENTATION OF THE BRONCHIAL TREE

Within the pulmonary parenchyma, a segmental bronchus gives rise to large and small subsegmental bronchi. A small subsegmental bronchus is continuous with a bronchiole. This transition involves the loss of cartilage plates in the bronchiole and a progressive increase in the number of elastic fibers.

The intrapulmonary segmentation results in the organization of a pulmonary lobule and a pulmonary acinus (Figure 13-7; see also Figure 13-6).

Figure 13-7 Histology of the intrapulmonary bronchial tree

Pulmonary lobule and pulmonary acinus

A terminal bronchiole and the associated region of pulmonary tissues that it supplies constitute a pulmonary lobule (Figure 13-8). A pulmonary lobule includes the respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli.

Figure 13-8 Pulmonary acinus

Physiologists designate the pulmonary acinus as the portion of the lung supplied by a respiratory bronchiole. Therefore, respiratory acini are subcomponents of a respiratory lobule. In contrast to the acinus, the pulmonary lobule includes the terminal bronchiole.

The pulmonary lobule–acinus concept is important for understanding the types of emphysema—permanent enlargement of the air spaces distal to the terminal bronchioles, associated with the destruction of their walls.

Distal to the respiratory bronchiole is the alveolar duct. The alveolar duct is characterized by an interrupted wall with typical smooth muscle knobs bulging into the lumen (Figure 13-9).

Figure 13-9 Transition from terminal bronchiole to respiratory bronchiole

At the distal end, the smooth muscle knobs disappear and the lining epithelium is primarily type I alveolar epithelial cells. Alveolar ducts branch to form two or more alveolar sacs. Alveolar sacs are formed by the alveoli, the terminal part of the airway.

Clinical significance: Emphysema

Chronic obstructive pulmonary disease (COPD) is characterized by progressive and often irreversible airflow limitations. COPD includes emphysema and asthma.

COPD occurs in the peripheral airways—the bronchioles—and lung parenchyma. Elastic fibers are important components of bronchioles and alveolar walls. A loss of elasticity and breakdown of elastic fibers give rise to emphysema, characterized by chronic airflow obstruction. As a result, adjacent alveoli become confluent, creating large air spaces, or blebs (Figure 13-10).

Figure 13-10 Elastic fibers and emphysema

Terminal and respiratory bronchioles are also affected by the loss of elastic tissue. As a result of the loss of elastic fibers, the small airways tend to collapse during expiration, leading to chronic airflow obstruction and secondary infections.

Let us review the concepts of the pulmonary lobule and the acinus to understand the types of emphysema. Figures 13-6 and 13-8 show that a pulmonary lobule includes the terminal bronchiole and the first to third generations of derived respiratory bronchioles. Each respiratory bronchiole gives rise to alveolar ducts and alveoli, an arrangement known as the acinus—so called because aggregates of alveoli cluster like acini in connection with the ductlike respiratory bronchiole. Because a pulmonary lobule generates several respiratory bronchioles, each resolved into an acinus, a pulmonary lobule is made up of several acini.

Centriacinar (or centrilobular) emphysema originates when the respiratory bronchioles are affected. The more distal alveolar duct and alveoli are intact. Thus, emphysematous and normal air spaces coexist within the same lobule and acini.

In panacinar (or panlobular) emphysema, blebs are observed from the respiratory bronchiole down to the alveolar sacs. This type of emphysema is more common in patients with a deficiency in the α₁–antitrypsin gene encoding a serum protein.

Protein α₁-antitrypsin is a major inhibitor of proteases, in particular elastase, secreted by neutrophils during inflammation (Figure 13-11). Under the influence of a stimulus, such as cigarette smoke, macrophages in the alveolar wall and alveolar lumen secrete proteases and chemoattractants (mainly leukotriene B₄) to recruit neutrophils.

Figure 13-11 Elastase and emphysema

Chemoattracted neutrophils appear in the alveolar lumen and wall and release elastase, normally neutralized by α₁–antitrypsin. Chronic smokers have low serum levels of α₁-antitrypsin, and elastase continues the unopposed destruction of elastic fibers present in the alveolar wall. This process develops in 10% to 15% of smokers and leads to emphysema.

Asthma is a chronic inflammatory process characterized by the reversible narrowing of the airways (bronchoconstriction) in response to various stimuli. The classic symptoms of asthma are wheezing, cough, and shortness of breath (dyspnea).

Emphysema differs from asthma in that the abnormalities limiting airflow are predominantly irreversible and a destructive process targets the lung parenchyma.

Clinical significance: Asthma

Asthma is characterized by airway hyperresponsiveness, defined by three salient features (Figure 13-12): (1) airway wall inflammation involving neutrophils, T cells (CD8⁺), and macrophages. Asthma is characterized by the recruitment of T cells (CD4⁺) and eosinophils (see Figure 13-12); (2) luminal obstruction of airways by mucus, caused by hypersecretion of bronchial mucous glands, along with infiltration by inflammatory cells; and (3) vasodilation of the bronchial microvasculature with increased vascular permeability and edema.

Figure 13-12 Pathogenesis of asthma

Asthma can be triggered by repeated antigen exposure (allergic asthma) or by an abnormal autonomic neural regulation of airway function (nonallergic asthma).

The pathophysiologic aspects of asthma appear to result from the aberrant proliferation of CD4⁺ helper Th2 cells producing three cytokines: interleukin (IL)-4, IL-5, and IL-13. IL-4 stimulates immature T cells to develop into the Th2 cell type, which produces IL-13 to precipitate an asthma attack.

Nonciliated Clara cells

Clara cells are epithelial cells with a dome-shaped apical domain lacking cilia. They represent 80% of the epithelial cell population of the terminal bronchiole (Figure 13-13). Clara cells secrete surfactant that differs from that produced by type II alveolar cells. After airway injury, Clara cells can proliferate and migrate to replenish alveolar epithelial cells. This process is known as alveolar bronchiolization More recently, Clara cells have been associated with Cl⁻ release mediated by a chloride channel regulated by a cyclic guanosine monophosphate (cGMP)– guanylyl cyclase C mechanism.

Figure 13-13 Structure and function of Clara cells

Clinical significance: Cystic fibrosis

Cystic fibrosis is a recessive genetic disease affecting children and young adults. Cystic fibrosis is caused by mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR), which results in reduced chloride secretion, increased sodium absorption, and insufficient airway luminal fluid (Figure 13-14).

Figure 13-14 Cystic fibrosis

These alterations in the respiratory and gastrointestinal tracts result in: (1) deficient mucus clearance, which determines a chronic cycle of infection, inflammation, and injury; and (2) the formation of a mucus gel matrix with reduced pore size, which consists of highly entangled polymeric MUC5AC and MUC5B molecules infiltrated with pathogens and immobilized neutrophils that might otherwise clear the infection.

Respiratory disease results from the obstruction of the pulmonary airways by thick mucus plugs, followed by bacterial infections. Cough, chronic purulent secretions, increased numbers of mucin-secreting cells in the submucosal glands, and dyspnea are typical symptoms of this COPD. These events are manifested radiographically as bronchiectasis (localized widening of bronchi).

In most patients, the blockage of pancreatic ducts by mucus causes pancreatic dysfunction. Pancreatic ductules release a bicarbonate-rich fluid under regulation of secretin. Secretin is produced by enteroendocrine cells in response to acidic gastric contents entering the duodenum (see Chapter 17, Digestive Glands).

In the skin, the excessive presence of salt secretion by sweat glands is diagnostic of cystic fibrosis (see Chapter 11, Integumentary System).

Treatment of the disease consists of physical therapy to facilitate bronchial drainage, antibiotic treatment of infections, and pancreatic enzyme replacement.

The cystic fibrosis gene encodes the protein CFTR, belonging to the ABC transporter family—so called because it contains adenosine triphosphate (ATP)– binding domains, or ATP-binding cassettes, and requires ATP hydrolysis to transport ions, sugars, and amino acids. In 70% of patients with cystic fibrosis, the amino acid 508—of a total of 1480 amino acids in CFTR protein—is missing.

As a member of the ABC transporter family, CFTR is rather unusual because it appears to require both ATP hydrolysis and cyclic adenosine monophosphate (cAMP)–dependent phosphorylation to function as a Cl⁻ channel.

Inherited mutations of CFTR in patients with cystic fibrosis result in defective chloride transport and increased sodium absorption. The CFTR channel also transports bicarbonate ions. Inherited mutations of CFTR are associated with reduced bicarbonate transport, resulting in excessive mucin cross-linking by calcium.

RESPIRATORY PORTION OF THE LUNG

Terminal bronchioles give rise to three generations of respiratory bronchioles (0.5 to 0.2 mm in diameter).

Respiratory bronchioles represent the transition from the conducting to the respiratory portion of the lung (Figure 13-15). They are lined initially by simple cuboidal epithelial cells, some of which are ciliated. The epithelium becomes low cuboidal and nonciliated in subsequent branches. The respiratory bronchiole subdivides to give rise to an alveolar duct (see Figure 13-15). The alveolar duct is continuous with the alveolar sac. Several alveoli open into an alveolar sac.

Figure 13-15 Subdivisions of the respiratory bronchiole: Alveolar duct, alveolar sac, and alveoli

The alveolus is the functional unit of the pulmonary acinus

About 300 million air sacs, or alveoli, in each lung provide a total surface area of 75 m² for oxygen and carbon dioxide exchange. Each alveolus has a thin wall with capillaries lined by simple squamous epithelial cells (Figure 13-16) forming part of the air-blood barrier (Figure 13-17).

Figure 13-16 Structure of the alveolus

Figure 13-17 Air-blood barrier

The alveolar epithelium consists of two cell types (see Figures 13-16 and 13-17): (1) type I alveolar cells, representing about 40% of the epithelial cell population but lining 90% of the alveolar surface; and (2) type II alveolar cells, approximately 60% of the cells, covering only 10% of the alveolar surface area.

Each alveolus opens into an alveolar sac. However, a few of them open directly into the respiratory bronchiole (see Figure 13-15). This particular feature distinguishes the respiratory bronchiole from the terminal bronchiole, whose wall is not associated with alveoli.

The low cuboidal epithelium of the respiratory bronchiole is continuous with the squamous type I alveolar cells of the alveolus (see Figure 13-9).

Additional cells of the alveolar septa are the alveolar macrophages (Figure 13-18) (also called dust cells; they are derived from bone-marrow monocytes and frequently seen in the alveolar lumen), fibroblasts (producing elastic fibers), and mast cells.

Figure 13-18 Macrophages and lymph drainage

Alveolar capillaries are lined by continuous endothelial cells juxtaposed to type I alveolar cells through a dual basal lamina produced by these two cells. Alveolar endothelial cells contain angiotensin-converting enzyme for the conversion of angiotensin I to angiotensin II (see Figure 14-18 in Chapter 14, Urinary System).

Type II alveolar cells

Type II alveolar cells are predominantly located at the angles formed by adjacent alveolar septa. Contrasting with the more squamous type I alveolar cells, type II alveolar cells are polygonal-shaped, vacuolated and extend beyond the level of the surrounding epithelium.

The free surface of type II alveolar cells is covered by short microvilli. The cytoplasm displays dense membrane-bound lamellar bodies, representing secretory granules containing pulmonary surfactant (Figure 13-19).

Figure 13-19 Type II alveolar cell

Surfactant is released by exocytosis and spreads over a thin layer of fluid that normally coats the alveolar surface. By this mechanism, the pulmonary surfactant lowers the surface tension at the air-fluid interface and thus reduces the tendency of the alveolus to collapse at the end of expiration. Clara cells, located in terminal bronchioles, also secrete pulmonary surfactant.

The pulmonary surfactant contains (1) phospholipids, (2) cholesterol, and (3) proteins (see Figure 13-19).

Specific surfactant proteins (SPs) consist of one hydrophilic glycoprotein (SP-A) and two hydrophobic proteins (SP-B and SP-C).

Within the lamellar bodies, SP-A and SP-B transform the phospholipid dipalmitoylphosphatidylcholine (DPPC) into a mature surfactant molecule.

In the alveolar space, SP-B and SP-C stabilize the phospholipid layer and enhance the surfactant action of the phospholipid DPPC–protein complex (Figure 13-20).

Figure 13-20 Macrophages: degradation of alveolar surfactant and asbestosis

Surfactant turnover is facilitated by the phagocytic function of alveolar macrophages (see Figures 13-18 and 13-20). Macrophages can also take up inhaled asbestos and trigger interstitial pulmonary fibrosis, asbestosis, characterized by extensive deposition of collagen and asbestos bodies (asbestos fibers coated by iron particles, see Figure 13-20). The alveolar spaces are generally uninvolved but type II alveolar cells increase in number (hyperplasia),

An additional function of type II alveolar cells is the maintenance and repair of the alveolar epithelium when injury occurs. When type I alveolar cells are damaged, type II alveolar cells increase in number and differentiate into type I alveolar-like cells (see Figure 13-20). As already discussed, Clara cells also have a reparative function during injury of the alveolar epithelium (alveolar bronchiolization).

Clinical significance: Acute respiratory distress syndrome

The significance of the cell components of the alveolus becomes clear when we analyze the relevant aspects of the acute respiratory distress syndrome (ARDS).

ARDS results from a disruption of the normal barrier that prevents leakage of fluid of the alveolar capillaries into the interstitium and alveolar spaces.

Two mechanisms can alter the alveolar barrier. In the first mechanism, an increase in hydrostatic pressure in the alveolar capillaries—caused, for example, by failure of the left ventricle or stenosis of the mitral valve—results in increased fluid and proteins in the alveolar spaces. The resulting edema is called cardiogenic or hydrostatic pulmonary edema.

In the second mechanism, the hydrostatic pressure is normal, but the endothelial lining of the alveolar capillaries or the epithelial lining of the alveoli is damaged. Inhalation of agents such as smoke, water (near drowning), or bacterial endotoxins (resulting from sepsis); or trauma can cause a defect in permeability. A cardiac component may or may not be involved. Although the resulting edema is called noncardiogenic, it can coexist with a cardiogenic condition.

A common pathologic pattern of diffuse alveolar damage (Figure 13-21) can be observed in cardiogenic and noncardiogenic ARDS. The first phase of ARDS is an acute exudative process defined by interstitial and alveolar edema, neutrophil infiltration, hemorrhage, and deposits of fibrin. Cellular debris, resulting from dead type I alveolar cells, and fibrin deposited in the alveolar space form hyaline membranes (Figure 13-22).

Figure 13-21 Acute respiratory distress syndrome (ARDS) and pulmonary edema

Figure 13-22 Neonatal respiratory distress syndrome (RDS)

The second phase is a proliferative process in which alveolar cells proliferate and differentiate to restore the epithelial alveolar lining, returning gas exchange to normal in most cases. In other cases, the interstitium displays inflammatory cells and fibroblasts. Fibroblasts proliferate and invade the alveolar spaces through gaps of the basal lamina. The hyaline membranes either are removed by phagocytosis by macrophages or are invaded by fibroblasts.

The third phase is chronic fibrosis and occlusion of blood vessels. Because ARDS is part of a systemic inflammatory response, the outcome of the lung process depends on improvement of the systemic condition. The prognosis for return to normal lung function is good.

The diagnosis of ARDS is based on clinical (dyspnea, cyanosis, and tachypnea) and radiologic examination. Treatment is focused on neutralizing the disorder causing ARDS and providing support of gas exchange until the condition improves.

Pleura

The pleura consists of two layers: (1) a visceral layer and (2) a parietal layer.

The visceral layer is closely attached to the lung. It is lined by a simple squamous epithelium, called mesothelium, and consists of cells with apical microvilli resting on a basal lamina applied to a connective tissue rich in elastic fibers (Figure 13-23). This connective tissue is continuous with the interlobular and interlobar septa of the lung. The parietal layer is also lined by the mesothelium.

Figure 13-23 Blood supply and lymph drainage of the pulmonary lobule

The visceral layer seals the lung surface, preventing leakage of air into the thoracic cavity. The parietal layer is thicker and lines the inner surface of the thoracic cavity. A very thin liquid film in between the visceral and parietal layers permits the smooth gliding of one layer against the other.

Blood vessels to the visceral pleura derive from pulmonary and bronchial blood vessels (see Figure 13-23). The vascular supply to the parietal pleura derives from the systemic blood vessels. Branches of the phrenic and intercostal nerves are found in the parietal pleura; the visceral pleura receives branches of the vagus and sympathetic nerves supplying the bronchi.