2 Anatomy and Histology of the Lung Joseph F. Tomashefski, Jr., and Carol F. Farver

The lung is uniquely designed to accomplish its major functions of movement of air and the delivery of oxygen to and removal of carbon dioxide from the circul­ation. Pulmonary anatomic compartments are tightly integrated for this purpose, while redundancy of struc­tures and provisions for collateral ventilation and blood flow enable the lung to rapidly adjust to physiologic demands and meet the challenges imposed by disease. The intricate net-like connective tissue skeleton of the lung, with its intrinsic elasticity, enables the lung to func­tion as a cohesive unit. Protected by the rigid thoracic cage and sealed in a bellows-like chamber, the lung responds to cyclical volume and pressure fluctuations coordinated with contractions of the diaphragm and tho­racic muscles of respiration on the order of 16 breaths per minute.

Espousing the precept that an understanding of normal anatomy is essential for the recognition and appreciation of abnormal structure, this chapter on practical lung anatomy and histology provides the reader with a base­line for the evaluation of macroscopic, histologic, and ultrastructural changes imparted by disease. A working conception of regional lung anatomy at the gross and microscopic level is also essential for the accurate local­ization of lesions. For this purpose, fixation of the lung in the inflated state is optimal (see Chapter 1). Knowledge of normal lung structure is also crucial for understanding radiologic appearances and in making radiographic cor­relations, which have become an important adjunct in the assessment of lung biopsy samples.1,2

Perhaps more than any other organ, the lung lends itself to anatomic and physiologic correlations. With the normal anatomy as a starting point, the pulmonary pathologist is in an ideal position to develop an apprecia­tion of the way in which abnormal structure is reflected in deviant function. Excellent texts that correlate anatomy with respiratory physiology and pulmonary function tests are those by Bates and colleagues3 and Fishman and colleagues.4 Special morphologic techniques used in the study of the lung are presented in Chapter 1. The

20

quantitative expression of lung anatomy and its mor­phometric evaluation are discussed by Weibel and Taylor. 5

External Features

The right and left lungs, invested in the visceral pleura, reside in their respective hemithoracic cavities, separated by the heart and mediastinal structures and bordered inferiorly by the diaphragm. Because the size of the lung is dependent on its volume, lung weight is the usual mea­surement provided in anatomic descriptions. The normal weight range of each lung in an adult is roughly 300 to 450 g.6 Increased lung weight is an indication of conges­tion, edema, or inflammatory exudates. Lung volume, measured in the inflated state by water displacement, ranges from 3.5 to 8.5 L for both lungs.6,7 The right lung is slightly larger than the left by a volume ratio of 53% to 47%.6 Due to their elastic nature, the lungs shrink to approximately one-third their size when the thoracic cavity is opened.s

The lung is covered by a smooth glistening visceral pleura. The pleural membrane is translucent, but as it rests on the lung, the visceral pleural surface appears pink. With increasing age, the pleura invariably accumulates black pigment, the amount of which is a reflection of the degree of exposure to environmental particulates. Pigment tends to deposit in a reticular fashion along the pleurallymphat­ics and is usually accentuated in the upper lobe. Interest­ing patterns of pigmentation include linear deposition at the angles of the lobes, or accentuation along the rib indentations (Fig. 2.1). Nodular accumulation of pigment is associated with subpleural lymphoid aggregates. Gray thickening indicates pleural fibrosis that is frequently seen at the lung apex as the "apical fibrous cap" (see Fig. 30.10 in Chapter 30).9 The visceral pleura wraps around the lung and is reflected from the mediastinal pleura at the hilum and pulmonary ligament. Prominent pleural indentations include, on the right, grooves for the esophagus and supe-

2. Anatomy and Histology of the Lung 21

FIGURE 2.1. A. Lateral external viewof right lung. The horizontal fissure isincomplete anteriorly. Black pigmentis accentuated in the upper lobe,following the indentations of theribs. B. Pigment outlines the pleurallymphatics, which demarcate theboundaries of secondary lobules. Apigmented nodule is seen in the lowerlobe (arrowhead). Note also the lineardeposit of pigment (arrow) along theinferior angle of the middle lobe.

rior vena cava, and a cardiac impression. On the left sidethe cardiac impression is more pronounced and there isan indentation (the cardiac notch) in the area of thelingula. A prominent crook-shaped aortic groove is locatedsuperiorly and posteriorly to the left hilum. lO

Lobes and Fissures

The right lung is divided into three lobes-upper, middle,and lower-that are demarcated from one another by adiagonal (major) fissure that separates the lower from theupper and middle lobes, and a horizontal (minor) fissurethat separates the middle from the upper lobe (Fig. 2.1).11The left lung is composed of an upper and lower lobe sepa­rated by a single diagonal fissure. The lingula (L. tongue),which represents the anterior-inferior division of the leftupper lobe, overrides the left cardiac ventricle, and is thecounterpart of the right middle lobe. Although readilyaccessible by a mini-thoracotomy, routine biopsy of thelingula for diffuse pulmonary disease has been discouragedbecause the lingula, like the right middle lobe, frequentlyhas old pathologic or nonspecific changes not necessarilyrelated to the current disease process (see Chapter l)Y

Deviations in fissure anatomy and distribution, includ­ing accessory and partial fissures, are common.l3 Usuallythe anterior aspect of the horizontal fissure is incomplete,potentially allowing for collateral ventilation between theright upper and middle lobes (Fig. 2.1). Occasionally ahorizontal fissure separates the lingula from the rest ofthe left upper lobe forming a trilobed left lung (pseudo­right lung). Conversely, absence of the horizontal fissureproduces a bilobate right lung. Any segment of the lungmay be partially or completely segregated by an acces­sory (supernumerary) fissure, a relatively frequent

anomaly occurring in up to 50% of specimens.1.I3 Common

accessory fissures include the inferior accessory fissureof the right lower lobe, which isolates the medialbasal segment as the retrocardiac lobe (Fig. 2.2), and anaccessory fissure separating the superior segment ("dorsallobe") from the lower lobe basal segments, also said tobe more common on the right. 1

,13 From a practical stand­point, deviations in fissure formation are of greatest

FIGURE 2.2. Accessory fissure (AF) separating medial basal(MB) segment from the other basal segments of the right lung.LB, lateral basal segment.

22 IF. Tomashefski, Jr., and c.F. Farver

FIGURE 2.3. Azygos lobe. A. Azygos fissure (arrow) in themedial aspect of the right upper lobe visualized in a posteroan­terior (PA) chest x-ray. B. Medial view of right lung showing

importance to the radiologist, and to the surgeon whenplanning a lung resection.

A particularly interesting anomalous fissure, the azygosfissure, is a vertically oriented cleft dividing the apicalsegment of the right upper lobe, seen in approximately1% of anatomic specimens and 0.4% of chest radio­graphs. 14

.15 It is thought to be produced by the downwardinvagination of the azygos vein with its pleural invest­ment, thus forming a mesoazygous. 16 The segregatedportion of lung is termed the azygos lobe (Fig. 2.3). Theazygos fissure presents radiographically as an oblique lineacross the apical portion of the right upper lobe, termi­nating in a teardrop shadow that represents the azygosvein seen on end (Fig. 2.3A).1.15 The bronchial and arterialsupply of the azygos lobe arise from the apical or poste­rior segments of the right upper lobe. 16

Bronchopulmonary Segments

For localization of lesions it is important to understandthe anatomy of the bronchopulmonary segments. Asegment refers to that portion of lung supplied by a seg­mental bronchus (see below). 17 Except in situations ofaberrant fissures, bronchopulmonary segments do nothave defined anatomic boundaries, and a pathologistmust estimate the localization of a segment based on thesupplying airway. The bronchopulmonary segments are

segregated azygos lobe (arrow) superior to the main bronchus.The posterior aspect of the specimen is to the right.

listed in Table 2.1, and the usual segmental distributionof each lung is shown schematically in Figure 2.4. Theterminology of the bronchopulmonary segments is thatoriginally proposed by Jackson and Huber. 17 Comparedto the right lung, the apical and posterior segments of theleft upper lobe and the anterior and medial basal seg­ments of the left lower lobe are often each supplied by asingle bronchus, and are referred to as the apicoposteriorand anteromedial basal segments, respectively. The lingulais composed of a superior and inferior segment as com-

TABLE 2.1. Lobes and segments of the lung

Right lung Left lung

Lobe Segment Lobe Segment

Upper Apical (1)* Upper Apical' (1)Posterior (2) Posterior' (2)Anterior (3) Anterior (3)

Middle Lateral (4) Lingular Superior (4)Medial (5) Inferior (5)

Lower Superior (6) Lower Superior (6)Medial basal (7) Medial basal' (7)Anterior basal (8) Anterior basal' (8)Lateral basal (9) Lateral basal (9)Posterior basal (10) Posterior basal (10)

'The two segments are frequently fused and considered as a singlesegment.*Numbers in parentheses refer to the numbering of segments inFig. 2.4.

2. Anatomy and Histology of the Lung

FIGURE 2.4. Schematic of the segmental anatomy of the lungs(see Table 2.1 for orientation and a key to the numbering).The right lower lobe superior segment (6) and the left upperlobe posterior segment (2) are not visualized from this anteriorview.

pared to the medial and lateral segments of the rightmiddle lobe.

Bronchi

Branching Pattern

Just below the level of the aortic arch, the tracheal carinamarks the bifurcation of the right and left main bronchi.The left main bronchus angles 40 to 60 degrees off theoriginal course of the trachea and extends longer than theright main bronchus as it circumvents the left side of theheart. The right main bronchus deviates only 20 to 30degrees off the course of the trachea, following a nearlystraight path into the right lower lobe bronchus. Thestraighter course of the right main bronchus predisposesto aspiration in the upright position (see Chapter 5)YThe rigidity of the extrapulmonary bronchi is maintainedby cartilaginous C-rings.

In the right hilum the main bronchus (Figs. 2.4 and 2.5)divides into the right upper lobe bronchus and a shortsegment, the bronchus intermedius, which then dividesinto the middle and lower lobe bronchi. The upper lobarbronchus divides into the three segmental bronchi. Themiddle lobe bronchus divides into the medial and lateralsegmental bronchi. The right lower lobe bronchus is quiteshort due to the abrupt takeoff of the posteriorly directedlower lobe superior segmental bronchus at about the

23

level of the middle lobe bronchial origin. The lower lobebronchus then proceeds toward the more distal bifurca­tions of the four basal segmental bronchi (Fig. 2.4). Theleft main bronchus divides into upper and lower lobarbranches. The left upper lobe bronchus branches into asuperior division, which gives rise to apicoposterior andanterior segmental branches, and the inferior (lingular)division. 17 The lower lobe bronchus divides into the supe­rior segmental bronchus (as on the right) and continuesto the four basal segmental divisions.6.'7

The bronchi accompany the pulmonary arteries asbronchovascular bundles surrounded by a connectivetissue sheath. With each division the caliber of the airwaysnarrows. The number of airway divisions varies amonglobes. The axial pathway (from the main bronchus to theterminal bronchiole) may contain as many as 25 divisionsor as few as five airway generations (along shorter path­ways).6 Normally bronchi are not macroscopically visiblewithin 2cm of the visceral pleura.

Connective Tissue, Cartilage, andSmooth Muscle

Connective tissue and smooth muscle provide the basicstructure of the conducting airways. There are 16 to 20tracheal cartilage rings, each of which is a C-ring thatencircles approximately two thirds of the circumferenceof the trachea, leaving an opening on the posterior surfacethat allows for expansion of food boluses traveling withinthe adjacent esophagus.The rings are composed of hyalinecartilage that may calcify and ossify with age. The mostproximal and distal cartilage rings of the trachea differfrom the others. The first ring is bifurcated and attached

FIGURE 2.5. Hilar structures. Hilum of right lung showing rela­tionship of main bronchus (B), pulmonary artery (PA) and vein(PV), hilar lymph node (N), and inferior pulmonary ligament(L). The anterior aspect of the specimen is to the left.

24 J.F. Tomashefski, Jr., and c.F. Farver

FIGURE 2.6. A. Longitudinally oriented elastic fibers create striations in the intrapulmonary bronchial mucosa. Note adjacentpulmonary arterial branches (bronchovascular bundles). B. Microscopic detail of submucosal elastic bundle in large bronchus.

to the cricoid cartilage of the larynx. The last trachealcartilage is wider than the others with a triangular-shapedlower border with two semi-ring-shaped areas that giverise to the cartilages of the two major bronchi. 18 Inbetween each cartilaginous ring and on the posteriorsurface of the trachea and main bronchi, is a fibrous mem­brane composed of collagen and elastic fibers, the latterof which provide for some recoil from stretching duringbreathing.

Beginning in the main bronchi just proximal to thelobar bronchi, the bronchial cartilage is organized cir­cumferentially into haphazard irregular plates thatdecrease in size and areal density as the bronchi extendinto the lung (Fig. 2.4; also see Fig. 1.12 in Chapter 1).With the rapid decrease in the cartilage mass, the circularsmooth muscle bundles become the most prominentmural components in medium-sized bronchi, and it ishere that bronchoconstriction is most efficient. A fewfibers of longitudinal smooth muscle may be present,external to the circular smooth muscle. More peripher­ally, smooth muscle decreases in amount and becomesscarce in the terminal bronchiole. In chronic obstructivelung disease, smooth muscle proliferates centrifugallyand can be found prominently even around the orifice ofthe alveolar duct. Elastic fibers run longitudinally in thelarger bronchi (Fig. 2.6) and become helical toward theperipheral airways, like coiled metal springs, and thencontinue into the alveolar wall forming integrated finenetworks. The outer limits of the extrapulmonary con­ducting airways are poorly defined. Alveolar walls formthe outer limit of the intrapulmonary bronchi, bronchi­oles, and pulmonary arteries.

Bronchial Glands

Mucoserous glands are present in the submucosa ofthe trachea and bronchi. These submucosal glands con­tain both mucous cells and serous cells, both of whichcontribute to the secretions of the mucous bilayer cover­ing the bronchial epithelium (Figs. 2.7 and 2.8). Thesemucinous secretions contain bacteriostatic lysozymesand lactoferrins, antibodies (immunoglobulin A, IgA)from the surrounding plasma cells, and some antiprote­ases. In older individuals glandular cells may be largelyreplaced by oxyphil cells (oxyphil metaplasia) (Fig. 2.8B).Approximately one opening of the duct of the bronchialgland can be found in a I-mm-square area in largehuman bronchi. Ciliated cells usually extend into theduct for a short distance (Fig. 2.8e). The bronchial ductdivides into one or more generations, depending onthe size of the gland, before reaching the glandular acinus.Myoepithelial cells line the secretory parts of the glandsand are controlled by the autonomic nervous system(Fig.2.8D).

The volume of the bronchial glands is estimated bythe gland-to-wall ratio (Reid index) or point-countingmethods on random light microscopic sections of a majorbronchus. The Reid index is calculated by measuring thethickness of the bronchial gland divided by the distancebetween the basal lamina of the bronchial mucosa andthe nearest perichondrium (Fig. 2.7B). For this determi­nation, a well-oriented bronchial cross section of a main­stem bronchus is necessary, and an average of severalmeasurements is optimal. For a practical estimation ofthe mucous gland mass, an "eyeball" estimate may suffice.

2. Anatomy and Histology of the Lung 25

FIGURE 2.7. Bronchial wall. A. Low magnification of the bronchial wall for orientation. 8. The Reid index is calculated as thepercentage of line A divided by line B (see text). (Elastic van Gieson [EVG].)

FIGURE 2.8. Seromucinous glands. A. Seromucinous gland.8. Oxyphil metaplasia involving a portion of the glandularlobule (arrow). C. High magnification of a ciliated intercalated

duct. D. Actin filaments ensheath the mucous gland. (Immuno­histochemical stain for muscle-specific actin.)

26

In patients without chronic bronchitis the Reid index isusually ~0.4.!9.20

Mucosa

The tracheal and bronchial mucosa is continuous with thelarynx and consists of a pseudostratified ciliated ~olum­

nar epithelium interspersed with goblet cells that SIt on abasement membrane. The bronchial basement membraneis a thin layer of extracellular matrix that provides supp~rtfor the epithelium. By light microscopy the bronchialbasement membrane measures approximately 7 j.tm inthickness?! The major molecular constituents are colla­gen IV, fibronectin, laminin-entactin/nidogen complexes,and proteoglycans.z1

-23 What appears as a homogeneo~s

basement membrane by light microscopy, however, ISactually a bilaminar structure consisting of the b~sal

lamina (true basement membrane) and the dee~er la~ma

reticularis. Thickening and fibrosis of the lamma retIcu­laris is characteristic of bronchial asthma.

The four major types of cells that make up the epithe­lium are (1) ciliated cells, (2) goblet cells, (3) basal cells,and (4). ne~roend~crine cells (Fi.g. ~.92!' Layer~d atop .t~eepithelIum IS the aIrway surface lIqUid that, wIth t~e cIlIa,comprise the mucociliary escalator that traps foreIgn par­ticles and organisms that enter the airways and propelsthem up and out of the conducting airways via thelarynx.24

Ciliated Cells

The main function of the ciliated cells of the mucosa isto propel foreign particles/organisms via the mucociliaryclearance mechanism. The number and importance ofciliated cells in the air passage are best illustrated by ascanning electron microscopic view of the surface of t.helarge bronchus, where cilia appear to cover the entIre

FIGURE 2.9. Light microscopic image of the bronchial mucosashowing the ciliated cells, rare goblet cells, and bronchial basalcells resting on a thin basement membrane.

IF. Tomashefski, Jr., and c.F. Farver

surface (Fig. 2.10). The ciliated cell in the large bronc~us

is up to 20/-lm in length and 10 /-lm in width, and cont~ms

about 200 cilia of 3 to 6/-lm in length on the lummalsurface. The nucleus is basal, and the cytoplasm is rich inmitochondria, which accumulate apically to supply energyfor cilia (Fig. 2.11). The size of the cell and the length ofthe cilia decrease as the diameter of the bronchusdecreases.

A cilium has an intracytoplasmic basal body that isenmeshed and stabilized in place by a fibrillary networkimmediately beneath the cell membrane. From the basalbody a long striated root extends and anchors deep in~o

the cytoplasm, and a basal foot aligns itself sideward mthe direction of the effective stroke of the cilium. At theneck, or the portion where the cilium emerges from thecell, the cell membrane forms a rosary-like modificationcalled the necklace. The cilium tends to break off but alsoregenerates itself from this neck portion. The main bodyof the cilium is formed by an axoneme surrounded by theextension of cell membrane. The axoneme consists of acentral pair and nine peripheral doublets of microtubules(see Fig. 5.41 in Chapter 5). Each doublet has a com~lete

tubule (A subfiber) and an attached three-quarter CIrcleof B subfiber. From the A subfiber, two rows of side arms(the inner and outer dynein arms) protrude to~ard theB subfiber of the adjacent doublet, and one radIal spokeextends toward the central pair. The dynein arms areformed by protein with high adenosine triphosphatase(ATPase) activity. At the distal e~d of .the c.ilium arehooking devices or bristles. (A detailed dIscussiOn of theultrastructure and pathology of the cilia is provided inChapter 5.) . .

The cilia extend into the overlying air surface lIqUid(ASL), which measures 5 to 100j.tm in thickness. The ASLis a bilayer of a low-viscosity or watery (sol) lower layer(a product of the serous and mucous glands in the submu­cosa), and a high-viscosity or gel ~ppe2~ layer .s~creted

from the goblet cells in the epithelIum. The CIlIa bendand beat back and forth by sliding opposing groups ofdoublets in opposite directions, which is accomplished byrepeated attachments and detachments of dyne~n ~rm~ toadjacent doublets, similar to the motions used m jackmgup a car. The recovery stroke of the ciliary beat is believedto be curved and to occur completely within the watery(sol) layer of the mucus. The effective stroke is done withcilia straight up, which allows the bristles to catch andpropel forward the gel or viscous mucus on top of the sollayer to the larynx where it can be expectorated. The rateof the ciliary beat is usually 12 to 16 beats/second andmetachronous25 and is coordinated by intercellular gapjunctions that allow for spread of this beat among theciliated cells.

Cilia and ciliated cells are constantly exposed andvulnerable to many noxious agents including cigarettesmoke. Therefore, ultrastructural ciliary changes are

2. Anatomy and Histology of the Lung 27

A B

FIGURE 2.10. By scanning electron microscopy (SEM), cilia completely carpet the luminal surface of large airways. The presence of nonciliated cells is not appreciated from the surface. A. Swine, x2500. B. Swine, xll,OOO. (Prepared by Dr. N.-S. Wang.)

common and varied; these include compound or fused cilia, deranged axonemes with supernumerary or missing micro tubules, internalized (cytoplasmic) or shed cilia, and other defects. (For a further discussion of cilia defects, see Chapter 5.)

Goblet Cells

The goblet cell is the most common nonciliated cell, and it extends from the larger bronchi to the smaller bronchi

FIGURE 2.11. Mitochondria accumulate adjacent to cilia in cili­ated cell. Long striated root (arrow) extends deeply from basal body of cilia. Human. Transmission electron microscopy (TEM) xll,OOO. (Prepared by Dr. N.-S. Wang.)

but is absent in the bronchioles. The ratio of ciliated to goblet cells is estimated to be between 7:1 and 25:1 in the large bronchi (Figs. 2.9 and 2.12).

The goblet cell has a basal nucleus, a well-developed rough endoplasmic reticulum, a Golgi apparatus, and abundant apical collections of mucous granules forming a "goblet" appearance (Fig. 2.13). The mucous granules are released into the bronchial lumen by the fusion and then the fenestration of the membranes of the granule and the cell, representing merocrine-type secretion. In excessive production and release, such as is seen in status asthmatic us, the apical portion of a goblet cell may appear to be completely replaced by an amorphous mass of mucus that extends in continuity from the cell into the mucous layer. Mucus in the lung, presumably like that in the intestine, is secreted for protection. It consists of acidic glycosaminoglycans, though the composition may vary during pathologic conditions. Goblet cells can divide mitotically and may increase in number drastically in any acute bronchial irritation, replacing almost all ciliated cells within 2 to 3 days. The recovery of ciliated cells is equally fast, and in chronic irritations certain balances develop between the two processes. Excessive goblet cell hyperplasia may disrupt the continuity of ciliary flow, and an excessive amount of mucus may obliterate the air passage, especially in small scarred airways. Although goblet cells contribute to the gel layer of bronchial mucus, the major source of mucus is the submucosal gland.

Basal Cells

All ciliated and nonciliated cells in the bronchial mucosa are derived from the basal cell. The basal cell of the

28

FIGURE 2.12. Ciliated cell is the most common cell type in bron­chial mucosa. Large goblet cell (G) appears pale. Darkly stained basal cell at bottom of mucosa is smaller than other tall colum­nar cells. Human. TEM, x2500. (Prepared by Dr. N.-S. Wang.)

bronchus is a pluripotential reserve cell that has a light and electron microscopic appearance similar to that of the epidermis. This cell is triangular with one of the broader sides firmly anchored on the basement membrane by hemidesmosomes (Fig. 2.12). The nucleus is large, and the organelles are scanty in the cytoplasm, which con­tains mainly loosely scattered ribosome complexes and tonofilaments. Desmosome complexes are prominent between cells.

Unlike the rest of the bronchial epithelium, the basal cell usually survives mucosal injuries to ensure a com­plete reconstruction of the bronchial mucosa. Prolonged irritation stimulates the proliferation of the basal cells (basal cell or reserve cell hyperplasia) or induces their differentiation into one or more differentiated forms. Deranged or mixed forms, which contain organelles of different types of cells, are also common, especially in the dysplastic and neoplastic epithelium that arise out of these cells (Fig. 2.14).

The Dense Core (Neuroendocrine) Cell and Neuroepithelial Bodies

See Chapter 36, Neuroendocrine Carcinomas, for a de­tailed discussion of neuroendocrine cells.

IF. Tomashefski, Jr., and c.F. Farver

Other Bronchial Lining Cells

Brush cells, also termed tuft, caveolated, multivesicular, and fibrillovesicular cells, are a special type of cell char­acterized by blunt microvilli and having disk- or rod-like inclusions of unknown functions. These cells have been identified from the nose to the alveoli in many species, but have not been found in humans except under certain disease states.26 The function of the pulmonary brush cell is obscure.

Bronchioles

A bronchus becomes a membranous bronchiole when cartilage completely disappears from its wall (Fig. 2.15). This occurs when the diameter of the airway decreases to about 1 mm. The terminal membranous bronchiole leads into the acinus, the functional unit of the lung, which con­sists of the respiratory bronchiole, alveolar ducts, alveolar sac, and alveoli (see below). The lung has approximately 30,000 terminal bronchioles, and each drains and concen­trates the contents of approximately 10,000 alveoli.

Membranous bronchioles (including the terminal bron­chiole) are lined completely by epithelial cells. This epi­thelium consists of ciliated columnar cells and nonciliated Clara cells. These bronchioles derive their mechanical support from the tethering effect exerted by the attached elastic fibers of the surrounding alveoli. Alveolar elastic fibers connect to the adventitia of the small airways and

FIGURE 2.13. Multiple mucous granules accumulate near apex of goblet cell with amorphous and reticular appearance. Human. TEM, xll,OOO. (Prepared by Dr. N.-S. Wang.)

2. Anatomy and Histology of the Lung

FIGURE 2.14. Mucous granules (0) and tonofilaments (T) are present within a dysplastic cell in bronchial mucosa. Human. TEM, x38,OOO. (Prepared by Dr. N.-S. Wang.)

help prevent the collapse of the small airways during the final phase of expiration (Fig. 2.15A). Their destruction in lungs with emphysema causes a premature collapse of these small airways and obstruction of the airflow (see Chapter 24).

The terminal bronchiole gives rise to the respiratory bronchiole, in which alveoli are present in the bronchiolar wall (Fig. 2.16). Usually there are three generations of respiratory bronchioles, although some variation between one and five generations is possible. Ciliated cells extend to the bronchioloalveolar junction. In these more periph­eral locations, they are short and decreased in number but maintain the continuity of the ciliary flow by a network arrangement around the nonciliated Clara cells (see below). This transitional zone is generally believed to be a normal lung structure, and formation of new alveoli in the small bronchioles is a normal process during the post­natal growth period, extending from birth until about 10 years of age. Direct epithelial-lined channels between membranous bronchioles and adjacent alveoli have been termed canals of Lambert (Fig. 2.15C). Depressions and eventual fistulous perforations of the wall of small mem­branous bronchioles also commonly occur in lung damage, especially in small-airway injury associated with tobacco use, leading to peribronchiolar proliferation and exten-

29

FIGURE 2.15. A. Membranous bronchiole with alveolar attach­ments. B. Wall of membranous bronchiole. Note single cell layer of ciliated epithelium and narrow fascicles of smooth muscle. C. Canal of Lambert. Narrow epithelial-lined channel (arrow) extends directly into adjacent lung parenchyma from a small membranous bronchiole.

30

FIGURE 2.16. Respiratory bronchiole and alveolar ducts. TB, terminal bronchiole; RBI, 2, and 3, three orders of respiratory bronchiole; AD, representative alveolar ducts.

sion of bronchiolar lining cells into the alveolar region ("Lambertosis").

Clara Cells

The Clara cell is a nonciliated cuboidal cell found in both the membranous and respiratory bronchioles that replaces the disappearing goblet cell in small bronchioles. The Clara cell has an apical surface that bulges into the lumen, is rich in endoplasmic reticulum and mitochon-

FIGURE 2.17. Electron micrograph of a Clara cell. Clara cells are taller than ciliated cells in small bronchioles. Note flame-shaped cytoplasmic processes rich in mitochondria, endoplasmic reticu­lum, and secretory granules. Mouse. TEM, x4500. (From Wang NS, Huang SN, Sheldon H, Thurlbeck WM. Ultrastructural changes of Clara and type II alveolar cells in adrenalin-induced pulmonary edema in mice. Am J Pathol 1971;62:237-252, with permission from the American Society for Investigative Pathology. )

IF. Tomashefski, Jr., and c.F. Farver

dria, and contains a prominent Golgi apparatus with apically located secretory granules that stain positively with periodic acid-Schiff (PAS)-diastase (Fig. 2.17). The Clara cells have been shown to secrete surfactant apopro­tein that serves to decrease the surface tension in this area of the lung and keep these small channels open.27 The Clara cell also serves as the reserve and reparatory cell in the small airways, a role similar to the basal cell more proximally and the alveolar type II cell more dis tally. 28

Parenchyma

Anatomic Subunits

Lobules

The secondary lobule of Miller is the smallest unit delineated by fibrous septa in the lung, and the smallest macroscopically observed unit of lung parenchyma.29 Each lobule measures from 1 to 2.5 cm in maximal dimen­sion and contains three to five acini (see below) (Fig. 2.18).6,30 In adult lungs the lobule is best observed in the peripheral subpleural areas where interlobular septa extend from the visceral pleura, incompletely demarcat­ing polyhedral units of lung parenchyma (Fig. 2.18A). Lobular architecture is much better defined in fetal or young children's lungs, especially in the upper lobe (Fig. 2.18B). The boundaries of the lobules are also readily recognized on the surface of the visceral pleura as the hexagonal pattern of lymphatic distribution (Fig. 2.1). Well-defined lobules are obscure in the central regions of normal adult lungs because the continued postnatal proliferation of alveoli stretches and disrupts the continuity of the interlobular septa. 12 Airways and pulmonary arteries enter the central portion of the lobule while pulmonary veins transport blood in the interlobular septa (Fig. 2.18e). The lobule is an important unit in chest radiology and histopathology, and some diseases such as emphysema are classified by their intra­lobular distribution of lesions (see Chapter 24). Inter­lobular septa are widened and accentuated in pulmonary edema and are visualized radiographically as Kerley B lines (see Fig. 28.42 in Chapter 28). With the advent of high-resolution chest computed tomography (CT) scans, the secondary lobule has assumed even greater impor­tance in the recognition of radiographic patterns of lung disease.2,31,32

The primary lobule of Miller, which refers to the distal portion of the acinus, originates from the last-order respiratory bronchiole and includes the divisions of the alveolar ducts, alveolar sacs, and attached alveoli (Fig. 2.19A). The primary lobule has been superseded by the acinus as the practical basic unit of lung anatomy (see below).6,3o,32

2. Anatomy and Histology of the Lung

FIGURE 2.18. A. Macroscopic view of lung parenchyma showing interlobular septa (arrows) demarcating secondary lobules. The visceral pleura is in the left upper corner (barium sulfate impregnation). B. Secondary lobules are prominently visualized in the lung of a 21-week gestational age fetus. C. Microscopic view of secondary lobules in an adult lung following pulmonary arterial injection of barium-gelatin contrast media. Interlobular septa are demarcated with arrows. Note filling of arteries in the centrilobular zone while veins are empty. Visceral pleura is at top. (EVG.)

31

Acinus

The pulmonary acinus is the unit of lung distal to the last conducting airway, the terminal bronchiole (Fig. 2.19).29,30 In lung casts, the acinus measures approximately 7.S x 8.S mm and consists of about three divisions of respira­tory bronchioles and several divisions of alveolar ducts, terminating in alveolar sacs with their grape-like clusters of alveoli. 1,29 In adults the number of alveoli within the acinus ranges from lS00 to 4000 alveoli.32 Acini have no septal boundaries, thus allowing for collateral ventilation, and they are not visible as defined units either grossly or microscopically (Fig. 2.19B). However, they have been delineated by means of corrosion casts.29,32 Historically the acinus has been important histopathologically in defining the intraparenchymal spread of tuberculous lesions, and in the classification of emphysema into cen­triacinar and panacinar variants.32 By virtue of the local­ization of bronchioles in the central portion of the lobule, the terms panacinar and centriacinar are synonymous with panlobular and centrilobular, respectively (see Chapter 24).32

Alveoli

Where alveoli completely replace the bronchiolar epi­thelial cells, the air passage, known as the alveolar duct, terminates in a semicircular blind end called the alveolar sac, which is surrounded by four or more alveoli.

The distal portion of the lung is formed by multifaceted and cup-shaped compartments called alveoli that have diameters of ISO to SOOf,lm (average, 2S0f,lm) (Fig. 2.20). In a 70-kg man, there are about 300 million alveoli with a gas-exchanging alveolar surface of approximately 143 m2 contained within an average lung volume of 4.3 L. After the age of 30 or 40 years the lungs undergo a pro­gressive dilatation of air spaces. Alveolar ducts enlarge while adjacent alveoli appear flattened (alveolar duct ectasia), although it is uncertain whether or not there is actual destruction of alveolar septa. It has been recom­mended that the term aging lung be used rather than the traditional term senile emphysema for aging-associated changes.33

The orifices of alveoli along the alveolar ducts and alveolar sacs are formed by thick elastic and collagen bundles that are the continuum of bronchial and bron­chiolar elastic bundles (Fig. 2.20B). From the orifice bundle, finer elastic fibers spread out further, resembling a basket, and are interwoven with capillaries. This network of elastic fibers and capillaries is plated (like wallpaper) on both sides by thin layers of type I alveolar lining cells. All elastic fibers, including the fine meshwork of the alveolus, are interconnected in all directions to form an integrated elastic network that is fundamental to the

A

32

_LOBULE 1

o LOBULE 2

LOBULE 3

• ATRIA

o DUCTULI ALVEOLARES

• BRONCHIOLI RESPIRATOR II B

• BRONCHIOLI RESPIRATORII A

• BRONCHIOLUS

FIGURE 2.19. A. Schematic view of the acinus beginning with the first respiratory bronchiole branching from a terminal bron­chiole. Within the acinus can be seen three primary lobules (I, II, III). B. Schematic depiction of an acinus from the terminal

FIGURE 2.20. Alveoli. A. Histologic section of several alveoli. B. Alveolus seen en face, stained for elastic tissue. Note thick elastic fibers rimming the alveolar orifice, and delicate thread-

B

J.F. Tomashefski, Jr., and c.F. Farver

membranous bronchiole (A) to branching orders of respiratory bronchioles and alveolar ducts (B). (A: From Miller,30 with permission. )

like fibers traversing the membrane. Neutrophils are seen in the ill-defined yellow capillary bed in the alveolar membrane. (Orcein elastic stain.)

2. Anatomy and Histology of the Lung

FIGURE 2.21. A. Ultrastructure of alveolocapillary membrane. (PI , type I pneumocyte; P2, type II pneumocyte; L, capillary lumen; E , capillary endothelial cell; Col, collagen bundles; IC, interstitial cell. B. Type I alveolar lining cell has a relatively large nucleus and thin, widely stretched cytoplasm (arrows) .

uniform expansion and elastic retraction of the lung in respiration.

Alveolar Lining Cells

There are two types of alveolar lining cells. The type I cell, which lies on the alveolar wall, can be likened to a fried egg, having a central flattened nucleus and a broad expanse of surrounding cytoplasm that reaches 50 f..lm in diameter and is as thin as 0.1 f..lm (Fig. 2.21). These cells numerically constitute only 40% of the alveo­lar lining cells but cover 90% of the alveolar surface.

A

FIGURE 2.22. A. Type II alveolar lining cell is cuboidal with large nucleus and nucleolus, many stubby microvilli, and abundant cytoplasmic organelles, including mitochondria, endoplasmic reticulum, Golgi apparatus, and characteristic osmiophilic

33

Thickened portion of alveolar wall contains an interstitial cell (IC) but air-blood barrier is very thin. Red blood cells and platelet in capillary. Mouse. TEM, xIS,DOO. (B: From Fraser and Pare,! with permission from Elsevier.)

The type I cells are joined by tight junctions and are underlined by a well-developed basal lamina, but have sparse surface microvilli and cytoplasmic organelles (Fig. 2.21).

In contrast, the type II alveolar lining cell, a cuboidal cell with a diameter up to 15 f..lm, possesses a large basal nucleus with a prominent nucleolus, and abundant osmio­philic lamellar inclusion bodies, the precursors of surfac­tant (Fig. 2.22). It constitutes 60% of the surface cells but covers only approximately 5% of the alveolar surface. Ultrastructurally, it has many stubby microvilli that project from its apical surface into the alveolar space

B

lamellar inclusion bodies. Human. TEM, xSOOO. B. Precursor of surfactant is being released from type II alveolar cell. Human. TEM, xIS ,OOO. (Prepared by Dr. N.-S. Wang.)

34

FIGURE 2.23. Surface of type II cell (B) shows abundant stubby microvilli. Microvilli sparse on type I cell (A) around alveolar pore. Human. SEM, x1200. (Prepared by Dr. N.-S. Wang.)

(Figs. 2.22 and 2.23), well-formed tight junctions with the adjacent type I cell, an underlying basement mem­brane, and abundant cytoplasm with well-developed endoplasmic reticulum and Golgi apparatus. Besides secreting surfactant, the type II alveolar lining cell also serves as the reserve cell, maturing into the type I cell normally. The type II alveolar lining cell is more resistant to injury than the type I pneumocyte and becomes hyper­plastic in response to alveolar damage; it may also become dysplastic (see the discussion of acute lung injury in Chapter 4) .

Surfactant

The type II alveolar cell secretes its osmiophilic lamellar inclusion bodies into the alveolar space (Fig. 2.22) to form a partially crystallized hypophase of tubular myelin, which then spreads out into a thin layer of surfactant (Fig. 2.24). Surfactant is formed mainly by phospholipids, especially dipalmitoyl lecithin, with the addition of gly­coprotein components. When the alveolus deflates, the phospholipids are compressed and aligned into a layer with hydrophilic and hydrophobic ends on each side at the air-liquid interface. This arrangement reduces the surface tension and prevents the collapse of the alveolus. At alveolar inflation, the orderly arrangement of the phospholipid molecules is disrupted, and the resulting increase in the surface tension assists the elastic recoil of the alveolus in expiration. The replenishment of surfac­tant about the alveolus and its presumed ascending flow

J.F. Tomashefski, Jr. , and c.F. Farver

toward the bronchiole is also helpful in alveolar clear­ance. Surfactant, therefore, plays several important roles in the stability and function of the alveolus.34

Insufficient production of surfactant in prematurity results in hyaline membrane disease with alveolar col­lapse and pulmonary edema (see Chapter 7). In diffuse alveolar damage syndrome at any age, excessive leakage of fibrin and other capillary contents into the alveolar space interferes with the action of surfactant despite a normal or even increased amount of surfactant in the alveolus (see Chapter 4).

Air-Blood Barrier

For the most efficient exchange of oxygen and carbon dioxide between air spaces and red blood cells, the alveolar arrangement is ideal. The alveolar interstitial cells and interstitial fibers are minimal (Fig. 2.21) , and a rich interanastomosing network of capillaries bulges into adjacent air spaces. It is estimated that 85% to 95% of the approximately 140m2 of alveolar surface is covered with the pulmonary capillary network, giving an air-blood interface of about 126m2, a surface area about 70 times that of the skin.

The endothelial and epithelial alveolar type I cell cyto­plasm is spread as thinly as possible and the basal laminae are fused, leading to an air-blood barrier with a mean thickness of 0.6Ilm. Plasma and other red cells may increase this distance in reality. Considering that a red blood cell has an average diameter of 71lm, one can appreciate the delicacy of these interfaces as well as how easily they might be damaged.

About 200 mL of blood are within the capillary network at any given time. Spread over 126m\ this is equivalent to about 1.6mL of blood (approximately 1 teaspoon) spread over 1 m2 ! Only about a third of the capillary network is functioning in the resting state, but it opens up extensively with exercise. The blood passes through this capillary bed in 0.75 seconds, and the flow must con­tinue to move to handle the entire cardiac output. The combined weight of the two lungs in vivo is approxi­mately 900 g, of which half consists of blood in the arter­ies, capillaries, and veins.

Capillary Endothelium

The pulmonary endothelium of the alveolus, which occu­pies a surface area of more than 140m2, is the largest and most dense vascular bed in the human body (Fig. 2.21). The fine structure and permeability of the alveolar capil­lary endothelium is similar to that of the capillary endo­thelium elsewhere in the body. Endothelial cells are connected to each other by loose junctions, compared to the tight junctions of alveolar epithelial cells, and there­fore more readily allow the passage of fluids and macro­molecules into the interstitial compartment.35.36

2. Anatomy and Histology of the Lung 35

FIGURE 2.24. Surfactant on alveolar surface has thin surface layer (top) and crystallized hypophase material with tubular myelin figure. Mouse. TEM, x45,OOO. (Prepared by Dr. N.-S. Wang.)

Besides serving as a barrier and actively regulating gas, water, and solute transport, the pulmonary endothelium also selectively processes and modifies a wide range of substances. A classic example is the conversion of angio­tensin I to angiotensin II and the inactivation of brady­kinin by angiotensin-converting enzyme; this reaction occurs in caveolae (pinocytic vesicles) and the microvilli of the luminal cytoplasmic membrane. The endothelium also clears serotonin, norepinephrine, prostaglandin E and F, adenine nucleotides, and some hormones and drugs, and releases angiotensin II, adenosine, some pros­taglandins, and previously accumulated drugs and metab­olites. It is of note that angiotensin II, epinephrine, and prostaglandins A and 12 are not altered by the pulmonary endothelium.35

The endothelia of pulmonary arteries and veins differ from the capillary endothelium in that the pulmonary arteries and veins are subjected to much greater changes in the vascular inner surface area than is the capillary. In resting or low-pressure conditions, the endothelium of pulmonary arteries appears elliptical with the long axis of the cell arranged parallel to the direction of the blood flow; the endothelium of pulmonary veins appears polyg­onal. Both of them have more surface microvilli and cytoplasmic organelles than the capillary endothelium, especially rod-shaped, membrane-bound structures (Weibel-Palade bodies), which probably are the storage site of the coagulation factor VIII.37

Other Cells and Structures in the Alveolar Wall

Mesenchymal cells, including fibroblasts, pericytes of cap­illaries, and myofibroblasts (contractile interstitial cells), are present in the alveolar septum adjacent to the capillary and constitute the "thick," non-gas-exchanging portion of the septum (Fig. 2.21). They are responsible for the main-

tenance and metabolism of the elastic and collagen fibers and proteoglycans in the alveolar walls. Collagen fibers, the rigid structural components of the lung (as opposed to its elastic fibers), are present mainly in the bronchovascu­lar bundles, intralobar and interlobular septa, and pleura. As the delicate collagen fibers in the normal alveolar wall can only be seen by electron microscopy, collagen fibers in alveolar walls that are apparent by light microscopy are abnormal. Contractile cells participate in the regulation of blood flow (see next section).

Neutrophils, eosinophils, lymphocytes, plasma cells, basophils or mast cells, and fixed or migratory macro­phages are present in small numbers in the alveolar wall and bronchial interstitial space. Neutrophils are most fre­quently found within the alveolar capillaries. Heavy sequestration and degranulation of neutrophils in the alveolar capillary may be responsible for insidious tissue lysis, such as elastolysis in pulmonary emphysema. An increase in the number of mast cells and eosinophils occurs in bronchial asthma or other hypersensitivity diseases.

Alveolar Regulation of Capillary Flow

The pulmonary blood flow is regulated mainly by small pulmonary arteries that constrict during hypoxia. Local regulation of the blood flow in the alveolar wall occurs via several possible mechanisms. The contractile interstitial cells are attached between adjacent endothelial and epi­thelial cells. When stimulated, they contract to distort and disrupt the capillary flow. The detailed control mechanisms, the mediators that induce their contraction, and the physi­ologic importance of this mechanism are not clear.

Another regulatory mechanism of the alveolar capillary flow is related to the interweaving of the elastocollagen

36

fibers and the capillaries. The capillary flow is disrupted at the extremes of inflation or deflation because of pinching of the capillaries in many places by the interlocking fiber network. While prolonged diffuse collapse or hyperinfla­tion of the lung is incompatible with life, interruption of blood flow to focally collapsed or overinflated alveoli is efficient and beneficia1.38

Alveolar Pores (of Kohn), Fenestrae, and Collateral Ventilation

Communications between adjacent alveoli are not present in the fetal lung. Pores (2 to 10).lm or more in size) start to appear in the alveolar wall soon after birth and appear to increase in number with age (Fig. 2.23). Normal alveo­lar pores are filled \\lith surfactant, thus blocking the airflow between adjacent alveoli. No normal function of the alveolar pores is known, but macrophages may wander through them. In classic lobar pneumonia, edema fluid, fibrin, and bacteria spread rapidly between alveoli through the alveolar pores, and at times tumor extends through them.

Alveolar pores larger than 15 ).lm, which are considered abnormal, are called fenestrae. Alveoli distal to an obstructed airway can receive collateral ventilation through fenestrae from alveoli ventilated by a nearby unobstructed bronchiole. Other collateral ventilation channels include communications between alveolar ducts or small bronchioles, and between bronchioles and alveoli (canals of Lambert). These structures are found most often in aged adult lungs, especially in diseased lungs.

A

FIGURE 2.25. A. Smokers' macrophages having a fine golden­brown cytoplasmic pigment. B. Faint iron staining in smokers' macrophages, not to be confused with hemosiderosis (Perls stain). C. Ultrastructure. Alveolar macrophage with surface

IF. Tomashefski, Jr., and c.F. Farver

Alveolar Macrophages

Alveolar macrophages (AMs) are terminally differenti­ated cells of the myeloid lineage. They are derived from bone marrow stem cells as monoblastic myeloid progeni­tors.39 In the presence of granulocyte-macrophage colony­stimulating factor (GM-CSF) and other cytokines the monoblasts are differentiated into monocytes in the blood.40 In the presence of continued stimulation with GM-CSF, these monocytes leave the circulation and enter the specific tissue where, based on the localized environ­ment, they become either activated as nonspecific imma­ture macrophages or differentiate into specific mature macrophages such as the alveolar macrophages in the lungs.4o

Alveolar macrophages are long-lived cells with life spans of many months up to several years. In­creases in the AM population during times of chronic irritation or inflammation occurs by two mechanisms: (1) increased number of blood monocytes moving into the lungs from the peripheral blood, and (2) prolif­eration of the local resident population of interstitial macrophages that divide and move into the alveolar space where they terminally differentiate into AMs fol­lowed by proliferation of the AMs in the alveolar space.41

Macrophages have elongated cellular processes called pseudopods, a well-developed endoplasmic reticulum and Golgi apparatus, membrane-bound structures that contain inflammatory mediators, and primary and sec­ondary lysosomes (Fig. 2.25). The macrophages move

microvilli, nucleus (N) and abundant cytoplasmic dense bodies containing lysosomes and phagolysosomes. Some of these het­erogeneous cytoplasmic inclusions contain lipid from metabo­lized surfactant (arrow). TEM, x9000.

2. Anatomy and Histology of the Lung

around on the alveolar and bronchiolar surfaces, may transgress the alveolar pore, and usually engulf exoge­nous and endogenous tissues and debris. Once in the air space, and especially after engulfing all the debris, mac­rophages probably do not migrate through the intact alveolar or bronchial epithelial layer back into the inter­stitium. Intravascular macrophages are rare in human lungs, and probably represent intravascular and submu­cosal clearance of noxious agents following the break­down of the normal epithelial and endothelial barriers by massive exposures.42 Alveolar macrophages either move by amoeboid motion or drift with the alveolar surfactant or fluid to reach the terminal bronchiole. They then are swept up with the surface fluid by cilia in the airway, to be finally swallowed or expectorated. Histologically, in cigarette smokers, abundant alveolar macrophages contain fine light brown pigment that may stain weakly for iron with histochemical stains such as Perls or Prus­sian blue (Fig. 2.25). Small intracytoplasmic, birefringent, silicate inclusions may also be seen (see Fig. 16.37 in Chapter 16).43

Bronchus-Associated Lymphoid Tissue

Bronchus-associated lymphoid tissue (BALT) refers to submucosal lymphoid aggregates associated with airways, and likely represents a component of the integrated sys­temic mucosa-associated lymphoid tissue (MALT) (e.g., Peyer's patches, appendiceal lymphoid tissue ).44 The lym­phoid aggregates involve airways at all levels but tend to be concentrated at the bifurcations of the bronchioles (see Fig. 32.3 in Chapter 32). Lymphoid aggregates occupy the lamina propria of the airway and are intimately asso­ciated with a specialized thinned overlying epithelial cell layer that readily facilitates antigen entry from the airway, and is readily infiltrated by lymphocytes. B cells, which stain immunohistochemically for IgM, IgG, or IgA, are the preponderant lymphocyte of BALT. The main secre­tory product is IgA.44 T cells, mainly CD4+ cells, comprise about 20% of the population. Plasma cells are rare and germinal centers are infrequently seen. Bronchus-associ­ated lymphoid tissue probably represents the site of local antibody production in response to antigen challenge from the airway.

Bronchus-associated lymphoid tissue has been identi­fied in about 50% of healthy infants and in nearly all fetuses and neonates with amniotic infection.45 It is better developed in certain animal species like the rodent, guinea pig or rabbit, than it is in humans. It is also increased and more readily apparent in the lungs of smokers than nonsmokers (see also Chapter 32 for a further discussion of BALT-associated lymphoprolifera­tive disease. )46

37

The Vasculature of the Lung

The lung has a dual blood supply: the pulmonary circula­tion and the bronchial (nutritional) circulation. The former is a low-pressure/high-capacity system that accommodates total systemic venous return and is struc­turally organized to absorb a large change of the flow volume with a minimal change in pressure. The bronchial arterial system, as part of the systemic circulation, deliv­ers blood at high pressure and of high arterial oxygen content.

Pulmonary Arteries and Veins

The pulmonary trunk arises from the right ventricle and quickly divides into left and right main pulmonary arter­ies, which further divide into lobar arteries before enter­ing the lung. As it enters the pulmonary hilum, the pulmonary artery is situated superiorly and slightly ante­riorly in relation to the pulmonary vein (Fig. 2.5).10 At this level the arteries and veins are of approximately the same caliber, the arteries appear light yellow, while the veins are gray. 6 The wall of the pulmonary artery is thinner than that of the aorta.

The main path of the pulmonary artery from the hilum to the peripheral lung is termed the axial pathway.47.48 Along this pathway the arteries follow and branch with the airways and at each level the arterial diameter is similar to that of the corresponding bronchus. Arteries can also be landmarked histologically by the adjacent airway. Pre acinar arteries are those accompanying airways to the level of the terminal bronchiole. More distal arter­ies are termed intraacinar.47,48 Conventional arteries are those that branch and taper with the bronchi as they penetrate into the lung. However, an even greater number of supernumerary arteries branch into the lung at both the preacinar and intraacinar level unaccompanied by airways.47

Histologically, the structure of the pulmonary arteries varies with the vascular diameter and location in the lung. Based on their structure, the arteries are of three major types: elastic, muscular, and nonmuscular. In adults the main pulmonary artery and distal branches down to a diameter of about 1000/lm have an elastic structure con­sisting predominantly of interrupted elastic fibers arranged circumferentially (Fig. 2.26A). This contrasts with the continuous circumferential pattern of elastic fibers seen in the aorta and in the pulmonary artery of the fetus and neonate. In situations of persistent pulmo­nary hypertension commencing at birth, the elastic pattern in the adult pulmonary artery may retain a continuous (aortic) configuration (see Chapter 28).49 As arteries extend into the lung, the elastic structure gives way to a muscular wall. Transitional arteries, roughly between 500 and 1000/lm in diameter, have a mixture of elastic and

38

FIGURE 2.26. Pulmonary vasculature (EVGs). A. Elastic pulmo­nary artery. Note interrupted pattern of elastic fibers. B. Mus­cular pulmonary artery. Note well-delineated internal and

muscle fibers in their walls. Arteries between 70 and 500/.lm in external diameter are of the muscular type in which circumferential smooth muscle fibers are bounded by a well-defined internal and external elastic lamina (Fig. 2.26B).49 In normal individuals muscular arteries are thin-walled; the ratio of the wall thickness to external diameter is on the order of 3% to 7%.49 From a diameter of about 30 to 150/.lm the continuous muscle coat gives rise to a spiral of muscle (Fig. 2.27). Arteries in this region are termed partially muscular and, on cross section, have a crescent of muscle forming a portion of the vascular wall.48 Arteries with an external diameter less than 70/.lm are mainly nonmuscular (i.e., arterioles) and feed directly into the alveolar capillaries.

Small intra acinar pulmonary venules have a nonmus­cular wall structure resembling pulmonary arterioles and usually cannot be discerned from arterioles without the

IF. Tomashefski, Jr., and c.F. Farver

external elastic laminae. C. Pulmonary vein. Mural elastic fibers merge with adventitial fibers. D. Bronchial artery. Note thick muscular wall and poorly defined external elastic lamina.

use of injection techniques (Fig. 2.18C) (see Chapter 1). The larger pulmonary veins, including those that enter and course in the interlobular septa, can be identified with elastic stains as having a well-defined internal elastic lamina and a thin, predominantly elastic wall structure without an external elastic lamina. The mural elastic fibers merge directly with those in the adventitia (Fig. 2.26C). In the veins, muscle fibers are sparse and irregu­larly arranged. In elderly individuals both arteries and veins may exhibit nonspecific intimal hyalinized fibrosis. 43

In situations of chronic pulmonary venous hypertension veins may acquire a thick medial muscle coat and a well­defined external elastic lamina (arterialization) (see Chapter 28). The small venules and lobular veins con­verge toward the hilum, forming larger pulmonary veins that congregate with the bronchi and pulmonary arteries at the segmental level, and proceed in their company to

2. Anatomy and Histology of the Lung

Cross section

Muscular

o

Partially muscular

o

Nonmuscular

Capil lary

o

FIGURE 2.27. Schema of distribution of muscle in intraparen­chymal pulmonary arteries (see text). (From Reid.48)

the hilum. The portion of the extrapulmonary vein near the left atrium is surrounded by cardiac muscle.

Bronchial Arteries and Veins

The bronchial arteries deliver the systemic nutrient blood supply to the lung, nourishing mainly the bronchi, pulmo­nary vasculature, and visceral pleura. The origin of the bronchial arteries varies considerably among individuals. They are usually located near the descending portion of the aortic arch at the origin of one of its major branches. The typical pattern consists of one bronchial artery on the right originating from the third intercostal artery and two on the left arising directly from the aorta. Within the lung the bronchial artery courses within the bronchial sheath and extends as far as the terminal bronchiole.!.5O In the normal lung the bronchial artery is very difficult to identify grossly since its diameter is only about 1.5 mm at the hilum.5! In chronic disease states, notably bronchi­ectasis and pulmonary hypertension, the bronchial arter­ies hypertrophy and may be grossly visible (see Chapter 5). Histologically the bronchial artery characteristically is a muscular artery with a well-defined internal elastica, but an absent or poorly defined external elastica, in con­trast to the well-defined internal and external elastica of muscular pulmonary arteries (Fig. 2.26D).6

The bronchial venous plexus is located along the airway sheath from the terminal bronchioles to the central bronchi. Intrapulmonary bronchial veins drain into the pulmonary veins representing a minor source of right to left shunt. The venous drainage of the central bronchi and tracheal bifurcation is via the systemic azygous and hemi­azygous veins into the right atrium.! Histologically, bron­chial veins resemble pulmonary veins.6

Two other sources of systemic blood supply to the lungs are small feeder arteries from the aorta in the infe-

39

rior pulmonary ligament (see Chapter 6) and arteries from a superior mediastinal plexus supplying the larger pulmonary veins.6.52.53

Vascular Shunts

Communications exist between arteries and veins of the pulmonary and bronchial systems. The best-documented communication is a postcapillary shunt between bron­chial and pulmonary capillaries and small veins. Preca­pillary bronchopulmonary anastomoses have been docu­mented mainly in fetuses and neonates.49.54.55 Their documentation and importance in adult lungs has been difficult to establish. The extent of shunting in the normal lung has been estimated to be less than 3% or up to 10% of the total cardiac output (see Fig. 6.6, Chapter 6).

In the course of evaluating precapillary bronchopul­monary anastomoses in fetal and neonatal lungs, Wagen­voort and Wagenvoort49 also encountered bronchopul­monary arteries (branches of bronchial artery that drain directly into alveolar capillaries) and pulmobronchial arteries (branches of the pulmonary artery that directly supply bronchi or perivascular connective tissue). Bron­chopulmonary arteries were mainly identified in fetuses, whereas pulmobronchial arteries were identified in fetal lungs and well as in those of neonates and older children. The normal role of pulmobronchial and bronchopulmo­nary arteries has not been well established.

In adult lungs, Pump55 documented numerous precapil­lary anastomoses between bronchial and pulmonary arteries using vascular injection and cast techniques. In earlier studies by von Hayek and Lapp, precapillary anas­tomotic vessels called sperrarterien were thought to act as muscular sphincters that regulated flow between the bronchial and pulmonary circuits. 56 Occasional thick­walled, hypermuscular vessels, probably representing sperrarterien, may be seen histologically (Fig. 2.28). Such an artery would be closed normally but would open, for example, during pulmonary embolism, to perfuse the ischemic lung tissue.

Following lung injury, repair, or neoplastic prolifera­tion, the altered tissue is vascularized by the bronchial artery and more shunts are created. The left-to-right shunt in the lung, therefore, increases with age and can be substantial in patients with neoplasms or destructive lung diseases such as tuberculosis and bronchiectasis (see Chapter 5). Systemic blood supply to the lung also assumes increasing importance in situations of pulmo­nary hypertension or proximal pulmonary artery obstruc­tion (see Chapter 28).50.57

Lymphatics

The lung has extensive networks of lymphatics, which are divided into the pleural, or superficial, plexus that drains

40

• ..

•

FIGURE 2.28. Hypermuscular artery in interlobular septum, probably representing a bronchopulmonary anastomosis (Sper­rarterien) (EVG).

the outer parts of the lung via the visceral pleural lym­phatics, and the deep, or parenchymal, plexus that drains in the bronchovascular bundles toward the hilar lymph nodes.6.58 Lymphatics are also richly present along the branches of the pulmonary veins in interlobular septa. The two lymphatic systems communicate with each other at the boundaries of their distribution and between lobes or lobules and the pleura near the hilum, but each system primarily drains separately toward hilar nodes in large lymphatic channels equipped with valves (Fig. 2.29).12

Lymphatic channels follow the bronchovascular bundle beginning at the level of the proximal respiratory bron­chiole. Alveolar walls do not have lymphatic spaces,

FIGURE 2.29. Dilated juxtavascular lymphatic channel showing lymphatic valve (arrow).

IF. Tomashefski, Jr., and c.F. Farver

although juxtaalveolar lymphatics in the small or distal bronchovascular bundle are partly facing and in contact with the basal surface of the adjacent alveolar epithelium and subepithelial connective tissue. 58

Lymphatic capillaries are lined by large flattened endo­thelial cells with few organelles. 59 Although all types of intercellular junctions are present, focally open or movable junctions devoid of basal lamina are unique to lymphatic capillaries. The collecting lymphatic channels resemble thin-walled veins with funnel-shaped, rather than bicuspid, valves. These valves, however, may appear bicuspid in histologic section (Fig. 2.29). In the normal lung, lymphatics are often collapsed and difficult to visu­alize histologically. In conditions of pulmonary edema or lymphangitis carcinomatosa, however, lymphatic chan­nels are dilated and readily observed (see Fig. 44.13 in Chapter 44).

Classically, it is said that the lymphatics of the right lung and left-lower lobe drain into the right lymphatic duct and those of the left upper lobe drain into the thoracic duct. 1 The thoracic duct drains most commonly into the left internal jugular vein. The right lympha­tic duct is an inconstant channel that may consist of mul­tiple fine branches that empty separately into the right jugular, subclavian, or innominate veins.1 Because of the intermixture of lymph flow in the interconnect­ing mediastinal lymphatic pathways, cross-drainage is frequent. 12

Lymph Nodes

Lymph nodes that drain the lung are by convention divided into four groups: (1) tracheobronchial lymph nodes adjacent to the trachea and main bronchi; (2) sub­carinallymph nodes located posterior to the main bron­chial bifurcation; (3) bronchopulmonary lymph nodes adjacent to lobar, segmental, and subsegmental bronchi; and (4) intrapulmonary lymph nodes, which are small lymph nodes located in the peripheral subpleural paren­chyma.6 Lymph node sampling is important in the staging of lung cancer, and the major lymph node anatomic sta­tions are illustrated in Chapter 35 (Fig. 35.18). Intrapul­monary lymph nodes are usually less than 1 cm in diameter and inconspicuous. With increasing dust accumulation or upon antigenic stimulation (especially in cigarette smokers), they may enlarge and present as a solitary nodule on the chest radiograph.6D Intrapulmonary lymph nodes are further discussed in Chapter 32. There is exten­sive collateral lymphatic circulation among lymph node groups in the pulmonary and mediastinal regions such that it is difficult to predict where metastatic tumor cells may deposit.6 The former concept that lymphangitis car­cinomatosa was the result of retrograde lymphatic flow of tumor cells into the lung from hilar and mediastinal

2. Anatomy and Histology of the Lung 41

FIGURE 2.30. A. Sinus histiocytosis resembling poorly formed granulomas. B. Hemosiderin bodies in lymph node. (Perls' stain.)

lymph nodes has been supplanted by the view that vas­cular spread of tumor to the lung followed by invasion of juxtavascular lymphatics, and antegrade spread to the bronchial lymph nodes is the major pathway of lymphatic permeation (see Chapter 44).61

Typically, bronchopulmonary lymph nodes in adults contain a variable degree of fine black pigment and grossly appear black or mottled black-gray. In situations of occupational dust exposure, increased pigment, along with silica and other dusts, may induce nodal fibrosis or silicotic nodules prior to the development of pulmonary pneumoconiosis (see Chapter 26),62 Ferruginous bodies may also be identified in lymph nodes following heavy inhalational exposure to asbestos (see Chapter 27).63.64

Lymph node follicular hyperplasia and sinus histiocy­tosis may be a cause of lymphadenopathy in bronchopul­monary lymph nodes as in other sites. Sinus histiocytosis at times has a nodular appearance simulating nonne­crotizing granulomas (Fig. 2.30A). In cases of chronic bronchopulmonary infection, such as cystic fibrosis, eryth­rophagocytosis may accompany sinus histiocytosis. Small yellow-brown oval structures, Hamazaki-Wesenberg bodies are also associated with sinus histiocytosis. These structures stain strongly with Gomori methenamine silver (GMS) stain and can be readily misidentified as histo­plasma yeast forms (see Fig. 18.24 in Chapter 18). Small ovoid hemosiderin bodies are also common in lymph nodes of lungs removed for cancer (Fig. 2.30B). These structures are of the size and shape of Hamazaki-Wesen­berg bodies, but are deep brown and stain intensely for iron. A variety of infectious and noninfectious granulo­matous diseases target the pulmonary and mediastinal lymph nodes, which may harbor fibrotic nodules and/or fibrocaseous granulomas as the residua of the prior infec­tion (see Chapters 9 and 10).

Nerves

The lung is innervated via the autonomic nervous system. Nerve trunks enter the lung at the hilum and are ar­ranged in two plexuses: periarterial and peribronchial. The peribronchial plexus is further divided into an extra­chondral and subchondral plexus according to its location relative to the bronchial cartilages.6s.66 The peribronchial plexus contains both myelinated and unmyelinated fibers, while the periarterial plexus contains only unmyelinated fibers.6s Ganglia are located mainly in the extrachondral plexus to the level of the distal bronchi (Fig. 2.31). Nerve

::. ..... , .

... ,

(

I,

-.

FIGURE 2.31. Neural ganglion is seen in the extra chondral plexus adjacent to bronchial artery and fibroelastic tissue of the outer perichondrium (left upper). (EVG.)

42

fibers also penetrate into the acinus and to the visceral pleura. Periarterial nerves continue to the level of the alveolar capillaries.66 Nerve fibers in the region of the alveolar septa are small and scarce (Fig. 2.32).5

The parasympathetic efferent (motor) fibers are derived from the vagus nerve and the sympathetic effer­ent (motor) fibers from the upper thoracic and cervical ganglia (Fig. 2.33).5,65 A third system, a nonadrenergic, non cholinergic (NANC) nervous system, is a neurally mediated bronchodilator pathway.

From the vagus, preganglionic parasympathetic fibers extend to ganglia located in and around the airway walls and around blood vessels.65 Postganglionic cholinergic parasympathetic fibers innervate the airway smooth muscle, glandular epithelium, and blood vessels, generally causing contraction of airway smooth muscle and increased secretion from the bronchial glands.66 Acetyl­choline mediates ganglionic transmission in the airways.67 Postganglionic adrenergic fibers from the cervical and thoracic sympathetic ganglia innervate the bronchial blood vessels and submucosal glands, but only sparsely innervate airway smooth muscle.67 Norepinephrine is the main adrenergic neurotransmitter.6 The most likely neu­rotransmitters in the NANC pathway are vasoactive intestinal peptide (VIP) and nitric oxide (NO).67

FIGURE 2.32. Terminal portion of nerve with small empty vesi­cles and mitochondria representing afferent cholinergic nerve ending (in alveolar wall [arrow». Human. TEM, x45,OOO. (Pre­pared by Dr. N.-S. Wang.)

IF. Tomashefski, Jr., and c.F. Farver

Afferent (sensory) nerve endings are present in the bronchial and alveolar walls, pleura, and the bronchial mucosa (Fig. 2.32).12,65 Sensory neurons may be located in the vagal ganglia or in the bronchial wall. Afferent nerve fibers travel to the central nervous system (CNS) via the vagus nerve. Within the airways, sensory nerves form specialized receptors such as slowly adapting stretch receptors (SAR), irritant receptors (rapidly adapting stretch receptors), and C fibers67; SARs are responsible for the Hering-Breuer reflex that inhibits further inspira­tion of air when the lungs are inflated and also modifies the normal pattern of breathing. Irritant receptors are concentrated in large central airways and are acti­vated by chemical and mechanical irritants. Their stimula­tion elicits defensive reflexes including cough. C fibers are unmyelinated and classified as either bronchial or pulmonary. Stimulation of either pulmonary or bronchial C fibers initiates a chemoreflex that includes bradycardia, hypotension, and apnea followed by rapid shallow breathing. Bronchial C fibers additionally induce bron­choconstriction, mucous hypersecretion, and cough. C fibers are especially sensitive to capsaicin, a pungent com­ponent of the hot capsicum pepper.67 A schematic summary of the innervation of the bronchial tree is seen in Figure 2.33.

The Pleural Cavity and Mesothelial Cells

The primitive body cavity or coelom, lined by mesothelial cells, appears early in the embryo (see Chapter 6). All constantly motile organs such as the lung, heart, and intestines bulge into this cavity during their development and are enveloped by the mesothelial cell layer as they do so. This arrangement renders all these organs not only readily movable but also pliable in size and shape during maturation. 12

The pleural and peritoneal cavities are normally com­pletely separated. They communicate with each other only indirectly through lymphatics. The pleural cavity is a potential space between the visceral pleura, which covers the entire surface of the lung including the inter­lobar fissures, and the parietal pleura, which covers the inner surface of the thoracic cage, mediastinum, and dia­phragm. The visceral pleura reflects at the hilum and pulmonary ligament to continue as the parietal pleura. The apposing two layers of mesothelial cells are sepa­rated only by a layer of hyaluronic acid-rich fluid less than 20l1m thick. The pleural recesses or sinuses are acutely angled portions of parietal pleura at the costo­phrenic or costomediastinal junctions. At the end of normal expiration functional residual capacity (FRC), the costophrenic sinus is a potential space that may extend up to the sixth or seventh intercostal space at the

2. Anatomy and Histology of the Lung

/

I , \

43

Epithelium

Mucous gland

Smooth muscle

Blood vessel

Bronchus

Bronchial ganglion

Dorsal root ganglion

V3gUS nerve

I Thoracic segment

of spinal cord

Thoracic and cervical ganglia

Inferior g3ngl ion •

Superior ganglion

Afferent (sensory)

Sympatheti c efferent

P3'3symp3thetic efferent

Medulla oblongata

FIGURE 2.33. Schematic illustration of bronchial innervation and neural pathways (see text).

posterior axillary line. 12 In inspiration, the lungs expand into this space. A needle introduced into the pleural space at these levels, especially at expiration, may easily pene­trate the two apposing layers of parietal pleura simulta­neously and enter the liver or other abdominal organs. The blood supply to the visceral pleura is from the bron­chial arterial system.50

The gross appearance of the pleura is that of a smooth, glistening, and semitransparent membrane. The macro­scopic features of the visceral pleura are fully described above in the section on external appearance of the lung. The parietal pleura is also smooth and shiny and tightly

adherent to the inner chest wall (Fig. 2.34). A variable amount of subpleural fat arranged in lobules overlying the ribs may be mistaken radiographically for pleural thickening or pleural plaques, and is more prominent in obese subjects.1.68 Pigment deposits of variable size can be seen on the parietal pleura in the majority of adult autopsies.69 Typical locations of pigment deposition are in the lower zones of the costal pleura.

By light microscopy the visceral pleura is divided into five layers: (1) a mesothelial layer, (2) a thin submesothe­lial connective tissue layer, (3) a superficial elastica layer, (4) a loose subpleural connective tissue layer, and (5) a

44

FIGURE 2.34. Macroscopic appearance of parietal pleura overly­ing the sternum and anterior portions of ribs. Black arrows indicate position of diaphragmatic attachment. White arrow designates lobule of submesothelial adipose tissue.

deep fibroelastic layer (Fig. 2.35).12.70 The presence and thickness of each layer varies regionally. The loose fourth layer is the plane of cleavage for decortication. The fifth layer frequently adheres tightly or bends into the paren­chyma of the lung as interlobular septa. The elastic fibers in this deep elastic (fifth) layer are interrupted and less conspicuous than those in the superficial layer, and extend into the alveolar septa of attached peripheral alveoli.

·A FIGURE 2.35. Pleura. A. Visceral pleura. The five pleural layers can be seen in this EVG-stained image (1, mesothelial cell layer; 2, sub mesothelial connective tissue layer; 3, outer elastic layer; 4, deep connective tissue layer; 5, inner elastic layer). B. Parietal

J.F. Tomashefski, Jr., and c.F. Farver

The parietal pleura is also covered by a similar layer of mesothelial cells under which is a thicker layer of fibroelastic tissue. Beneath this layer resides subpleural fibroadipose tissue and skeletal muscle of the chest wall (Fig. 2.35).6

The mesothelial cells are stretchable and range in size from 16.4 ± 6.8 to 41.9 ± 9.5 11m. They may appear flat, cuboidal, or columnar. Generally speaking, cuboidal or columnar cells are associated with a substructure that is loose or fatty, as in the pleural recesses, or indicate that the cells are metabolically active (see Fig. 30.2 in Chapter 30). Flattened cells usually represent stretched quiescent cells on the visceral surface or cover a very rigid substruc­ture such as a rib (see Fig. 30.1 in Chapter 30)Y

Mesothelial cells are characterized ultrastructurally by an abundance of elongated bushy microvilli O.lllm in length (see Fig. 30.3 in Chapter 30). The microvilli trap hyaluronic acid, which acts as a lubricant to lessen the friction between the moving lung and the chest wall. The cytoplasm is rich in pinocytotic vesicles, mitochon­dria, and other organelles and prekeratin fibrils (see Fig. 30.4 in Chapter 30). Mesothelial cells are connected by numerous desmosomes. The presence of dominant bushy microvilli aids in the ultrastructural identification of mesotheliomas (see Chapter 43).

The secretion and absorption of pleural fluid is gov­erned by Starling's law (see Chapter 28). Large particles and cells such as fibrin molecules or macrophages are removed through preformed stomas directly connecting the pleural cavity with lymphatics (see Fig. 30.5 in Chapter 30). The stomas are found only in specific areas of the parietal pleura including mediastinal and infracostal regions, especially in the lower thorax. The entry of large particles into a dilated lymphatic lacuna through the stoma is facilitated by respiratory movement. The roof of the lacuna is formed by a network of thick collagen

. . •

pleura. A prominent elastic fiber layer resides beneath the mesothelial cells and overlies submesothelial fibroadipose tissue. Dark-staining material on the pleural surface is fibrin. (EVG.)

2. Anatomy and Histology of the Lung

bundles that is covered by mesothelial cells on the pleural and endothelial cells on the lacuna side. These two layers of cells rupture readily in disease to increase the route of pleural clearance.

Pleural ultrastructure is further discussed in Chapter 30.

The Thorax

Thoracic Cage

The skeletal elements of the thorax consist of 12 thoracic vertebrae, 12 pairs of ribs, and the sternum. The clavicle is positioned above and in front of the first rib serving to protect the thoracic inlet and its major vessels and other vital structures. The adjacent vertebral bodies are sepa­rated by fibroelastic cartilaginous disks bound together by heavy ligaments and are further reinforced and made flexible by paravertebral musclesY The sternum consists of the manubrium, the body of the sternum, and the xiphoid process. The manubrial-sternal joint creates the sternal angle and is a hinge-like symphysis, which plays an important part in respiration, allowing the body of the sternum to move backward and forward. 71 The body of the sternum is composed of four bony plates (sternebrae) that fuse by synostosis during childhood. Posteriorly, the sternum is covered by parietal pleura, which can be the site of pleural plaques (Fig. 2.34). Common sternal anom­alies include a lower sternal angle between the first and second sternebrae (the usual anatomy in the gibbon), or a sternal foramen, resembling a central bullet hole in the body of the sternum due to failure of ossification.lO.71

Each rib is a semicircular, slightly angulated blade of bone, likened to a bucket handle that forms a joint with the body and the transverse process of the vertebra (the costovertebral joints). The anterior ends of the first 10 ribs are joined to the sternum by cartilage, the first seven directly and the next three indirectly by articulating with the cartilage of the rib lying immediately above. The 11th and 12th ribs usually remain unattached.1O•71 The costo­vertebral joints allow the anteriorly slanted ribs to elevate at inspiration and fall back passively at expiration.!2 The costal cartilages usually undergo a variable degree of ossification, typically referred to as "calcification" in the radiographic literature.1 The initial radiographic pattern of chondral calcification may appear either central (more common in women), peripheral (more common in men), or of mixed pattern (in approximately 7% of both sexes). Supernumerary ribs may occasionally occur at either the seventh cervical (seen in 1.5% of normal individuals) or first lumbar vertebrae. 14,71 Complete or partial fusion of ribs may produce confusing shadows on chest x-ray.!

The intercostal muscles seal the space between the ribs and costal cartilages. They contract with each respiratory movement to prevent the intercostal pleural membrane

45

from sinking in with inspiration or herniating outward with expiration. The external oblique components of the intercostal muscle also lift up the thoracic cage to increase the anterior posterior and transverse dimensions of the thorax while the diaphragm contracts to lengthen the thoracic space. Accessory inspiratory muscles include the sternocleidomastoid and scalenus muscles, which elevate the sternum and upper ribs in strenuous breathing. Expi­ration in quiet breathing is a passive relaxation of inspira­tory muscles aided by the natural recoil of the stretched elastic fiber network of the lung. Additional expiratory effect during active breathing is achieved by contraction of the internal oblique components of the intercostal muscles, which lower the ribs, thereby decreasing thoracic volume.!2

The blood supply to the ribs is via intercostal arteries that arise as branches from the internal mammary arter­ies that themselves arise from the subclavian artery and run parallel to the sternum. The intercostal artery and vein run together, along with the intercostal nerve, along the inferior edge of each rib under the shelter of the costal groove. lO,71 The intercostal arteries may serve as a source of collateral systemic circulation to the lung and pleura in situations of pulmonary emboli, pulmonary hypertension, or pleural inflammation. Venous drainage is via the internal mammary vein to the brachiocephalic vein.!O)1

Thoracic Inlet

The apical portion of each hemithorax represents a complex array of anatomic structures that, when invaded by malignant tumors in this region (such as mesothelioma or Pancoast tumor), may give rise to a variety of confusing symptoms (see Chapter 35). This region is also known as the thoracic inlet. The parietal pleura (cupola of the pleura, dome of the pleura) dually serves as the superior bound­ary of the thoracic cavity and the inferior boundary of the lower neck compartment. Major structures in this area include the subclavian artery and a few of its branches, the brachiocephalic vein, the phrenic nerve, the sympathetic trunk, and the lowest trunk of the brachial plexus.

The Diaphragm

The diaphragm is a dome-shaped muscle plate with a central tendon and peripheral radiating muscle fibers that separates thoracic and abdominal cavities. The sternal part attaches to the posterior surface of the xiphoid process (Fig. 2.34). The costal part attaches to the inner surfaces of the costal cartilages of ribs 7 to 12 bilaterally. The lumbar portion fuses into left and right crura and attaches to the upper lumbar vertebral bodies. The central tendon is divided into three leaflets, which lie in front of

46

and on either side of the vertebral column. The central tendon is a common location for asbestos-related pleural plaques.69 The diaphragm is pierced by the inferior vena cava in the area of the central tendon, and by the esopha­gus through the decussating fibers of the right crus. The aorta does not pierce the diaphragm but passes behind the median arcuate ligament at the level of the 12th ver­tebra. 1O·71 Areas of muscle deficiency, which constitute weak areas of the diaphragm, are located immediately behind the sternum (foramina of Morgagni) and along the posterolateral rib cage (foramina of Bochdalek).l

The diaphragm is supplied by the left and right phrenic nerves, which originate mainly from the fourth cervical nerve and descend from the cervical plexus over the surface of the pericardium to innervate the diaphragm. Unilateral elevation of diaphragm can occur from phrenic nerve damage along its long courseY

The dome of the hemidiaphragm, in its relaxed state at expiration, reaches approximately to the xiphoid process level (anterior fifth rib to interspace of the sixth rib). The dome of the right hemidiaphragm tends to be about half an interspace higher than that of the left. With contrac­tion, the diaphragm flattens, increasing the volume of the thoracic cavity. Fraser and Pare l found the mean excur­sion of the right and left hemidiaphragms to be 3.3 and 3.5 cm, respectively, while Young and Simon72 noted a range of excursion from 0.8 to 8.1 cm in healthy individuals.

The Mediastinum

The mediastinum is the intrathoracic, midline, pliable soft tissue compartment bordered superiorly by the thoracic inlet, laterally by the parietal pleura and lungs, anteriorly by the sternum, and posteriorly by the vertebrae. The mediastinum can be pushed toward the contralateral hemithorax by pleural effusion, tension pneumothorax, or other increases in the pleural content, and it can be pulled toward the ipsilateral side in atelectasis, pulmo­nary fibrosis, or surgical lung excision.

The mediastinum traditionally is separated into supe­rior, anterior, and posterior parts, and a middle part which contains the heart and the pericardium, serving as the reference unit. This classification is simple and useful in the differential diagnosis of mediastinal lesions: lympho­mas and thymic and thyroid tumors occur more frequently in the superior and anterior parts, neural tumors in the posterior region, and lymph nodes and metastatic tumors in the lateral portions of the middle mediastinum. For a detailed discussion of the anatomy of the mediastinum, the reader is referred to standard texts. l ,lO,71

Acknowledgments. The authors acknowledge the con­tribution of the late Dr. Nai-San Wang, who wrote the

IF. Tomashefski, Jr., and c.F. Farver

chapter on lung and pleural anatomy in the first two edi­tions of this text. Many of the electron micrographs used in the current chapter were prepared by Dr. Wang. The authors also acknowledge the secretarial assistance of Ms. Diane Gillihan and Ms. Mary Krosse, the photographic support of Mr. Vince Messina, and the staff of the Brit­tingham Memorial Library at MetroHealth Medical Center.

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