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Anatomy and Histology of the Lung

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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 circul-
ation. Pulmonary anatomic compartments are tightly
integrated for this purpose, while redundancy of struc-
tures 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 func-
tion 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 tho-
racic 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 base-
line 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 local-
ization 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 cor-
relations, 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 apprecia-
tion 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 colleagues 3 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 mor-
phometric 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 mea-
surement 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 conges-
tion, 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 pleurallymphat-
ics and is usually accentuated in the upper lobe. Interest-
ing 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 view

of right lung. The horizontal fissure is
incomplete anteriorly. Black pigment
is accentuated in the upper lobe,
following the indentations of the
ribs. B. Pigment outlines the pleural
lymphatics, which demarcate the
boundaries of secondary lobules. A
pigmented nodule is seen in the lower
lobe (arrowhead). Note also the linear
deposit of pigment (arrow) along the
inferior angle of the middle lobe.

rior vena cava, and a cardiac impression. On the left side anomaly occurring in up to 50% of specimens. 1.I 3 Common
the cardiac impression is more pronounced and there is accessory fissures include the inferior accessory fissure
an indentation (the cardiac notch) in the area of the of the right lower lobe, which isolates the medial
lingula. A prominent crook-shaped aortic groove is located basal segment as the retrocardiac lobe (Fig. 2.2), and an
superiorly and posteriorly to the left hilum. lO accessory fissure separating the superior segment ("dorsal
lobe") from the lower lobe basal segments, also said to
be more common on the right. 1,13 From a practical stand-
point, deviations in fissure formation are of greatest
Lobes and Fissures
The right lung is divided into three lobes-upper, middle,
and lower-that are demarcated from one another by a
diagonal (major) fissure that separates the lower from the
upper and middle lobes, and a horizontal (minor) fissure
that separates the middle from the upper lobe (Fig. 2.1).11
The left lung is composed of an upper and lower lobe sepa-
rated by a single diagonal fissure. The lingula (L. tongue),
which represents the anterior-inferior division of the left
upper lobe, overrides the left cardiac ventricle, and is the
counterpart of the right middle lobe. Although readily
accessible by a mini-thoracotomy, routine biopsy of the
lingula for diffuse pulmonary disease has been discouraged
because the lingula, like the right middle lobe, frequently
has old pathologic or nonspecific changes not necessarily
related to the current disease process (see Chapter l)Y
Deviations in fissure anatomy and distribution, includ-
ing accessory and partial fissures, are common. l3 Usually
the anterior aspect of the horizontal fissure is incomplete,
potentially allowing for collateral ventilation between the
right upper and middle lobes (Fig. 2.1). Occasionally a
horizontal fissure separates the lingula from the rest of
the left upper lobe forming a trilobed left lung (pseudo-
right lung). Conversely, absence of the horizontal fissure
produces a bilobate right lung. Any segment of the lung FIGURE 2.2. Accessory fissure (AF) separating medial basal
may be partially or completely segregated by an acces- (MB) segment from the other basal segments of the right lung.
sory (supernumerary) fissure, a relatively frequent LB, lateral basal segment.
22 IF. Tomashefski, Jr., and c.F. Farver

FIGURE 2.3. Azygos lobe. A. Azygos fissure (arrow) in the segregated azygos lobe (arrow) superior to the main bronchus.
medial aspect of the right upper lobe visualized in a posteroan- The posterior aspect of the specimen is to the right.
terior (PA) chest x-ray. B. Medial view of right lung showing

importance to the radiologist, and to the surgeon when listed in Table 2.1, and the usual segmental distribution
planning a lung resection. of each lung is shown schematically in Figure 2.4. The
A particularly interesting anomalous fissure, the azygos terminology of the bronchopulmonary segments is that
fissure, is a vertically oriented cleft dividing the apical originally proposed by Jackson and Huber. 17 Compared
segment of the right upper lobe, seen in approximately to the right lung, the apical and posterior segments of the
1% of anatomic specimens and 0.4% of chest radio- left upper lobe and the anterior and medial basal seg-
graphs. 14 .15 It is thought to be produced by the downward ments of the left lower lobe are often each supplied by a
invagination of the azygos vein with its pleural invest- single bronchus, and are referred to as the apicoposterior
ment, thus forming a mesoazygous. 16 The segregated and anteromedial basal segments, respectively. The lingula
portion of lung is termed the azygos lobe (Fig. 2.3). The is composed of a superior and inferior segment as com-
azygos fissure presents radiographically as an oblique line
across the apical portion of the right upper lobe, termi-
nating in a teardrop shadow that represents the azygos TABLE 2.1. Lobes and segments of the lung
vein seen on end (Fig. 2.3A).1.15 The bronchial and arterial Right lung Left lung
supply of the azygos lobe arise from the apical or poste- Lobe Segment Lobe Segment
rior segments of the right upper lobe. 16
Upper Apical (1)* Upper Apical' (1)
Posterior (2) Posterior' (2)
Anterior (3) Anterior (3)
Bronchopulmonary Segments Middle Lateral (4) Lingular Superior (4)
Medial (5) Inferior (5)
Lower Superior (6) Lower Superior (6)
For localization of lesions it is important to understand
Medial basal (7) Medial basal' (7)
the anatomy of the bronchopulmonary segments. A Anterior basal (8) Anterior basal' (8)
segment refers to that portion of lung supplied by a seg- Lateral basal (9) Lateral basal (9)
mental bronchus (see below). 17 Except in situations of Posterior basal (10) Posterior basal (10)
aberrant fissures, bronchopulmonary segments do not
'The two segments are frequently fused and considered as a single
have defined anatomic boundaries, and a pathologist segment.
must estimate the localization of a segment based on the *Numbers in parentheses refer to the numbering of segments in
supplying airway. The bronchopulmonary segments are Fig. 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 upper
lobe posterior segment (2) are not visualized from this anterior
view.
pared to the medial and lateral segments of the right
middle lobe.
Bronchi
Branching Pattern
Just below the level of the aortic arch, the tracheal carina
marks the bifurcation of the right and left main bronchi.
The left main bronchus angles 40 to 60 degrees off the
original course of the trachea and extends longer than the
right main bronchus as it circumvents the left side of the
heart. The right main bronchus deviates only 20 to 30
degrees off the course of the trachea, following a nearly
straight path into the right lower lobe bronchus. The
straighter course of the right main bronchus predisposes
to aspiration in the upright position (see Chapter 5)Y
The rigidity of the extrapulmonary bronchi is maintained
by 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 short
segment, the bronchus intermedius, which then divides
into the middle and lower lobe bronchi. The upper lobar
bronchus divides into the three segmental bronchi. The
middle lobe bronchus divides into the medial and lateral
segmental bronchi. The right lower lobe bronchus is quite
short due to the abrupt takeoff of the posteriorly directed
lower lobe superior segmental bronchus at about the
23
level of the middle lobe bronchial origin. The lower lobe
bronchus then proceeds toward the more distal bifurca-
tions of the four basal segmental bronchi (Fig. 2.4). The
left main bronchus divides into upper and lower lobar
branches. The left upper lobe bronchus branches into a
superior division, which gives rise to apicoposterior and
anterior segmental branches, and the inferior (lingular)
division. 17 The lower lobe bronchus divides into the supe-
rior segmental bronchus (as on the right) and continues
to the four basal segmental divisions. 6.'7
The bronchi accompany the pulmonary arteries as
bronchovascular bundles surrounded by a connective
tissue sheath. With each division the caliber of the airways
narrows. The number of airway divisions varies among
lobes. The axial pathway (from the main bronchus to the
terminal bronchiole) may contain as many as 25 divisions
or as few as five airway generations (along shorter path-
ways).6 Normally bronchi are not macroscopically visible
within 2cm of the visceral pleura.
Connective Tissue, Cartilage, and
Smooth Muscle
Connective tissue and smooth muscle provide the basic
structure of the conducting airways. There are 16 to 20
tracheal cartilage rings, each of which is a C-ring that
encircles approximately two thirds of the circumference
of the trachea, leaving an opening on the posterior surface
that allows for expansion of food boluses traveling within
the adjacent esophagus. The rings are composed of hyaline
cartilage that may calcify and ossify with age. The most
proximal and distal cartilage rings of the trachea differ
from the others. The first ring is bifurcated and attached
FIGURE 2.5. Hilar structures. Hilum of right lung showing rela-
tionship 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
FIGURE 2.6. A. Longitudinally oriented elastic fibers create striations in the intrapulmonary bronchial mucosa. Note adjacent
pulmonary arterial branches (bronchovascular bundles). B. Microscopic detail of submucosal elastic bundle in large bronchus.
to the cricoid cartilage of the larynx. The last tracheal
cartilage is wider than the others with a triangular-shaped
lower border with two semi-ring-shaped areas that give
rise to the cartilages of the two major bronchi. 18 In
between each cartilaginous ring and on the posterior
surface of the trachea and main bronchi, is a fibrous mem-
brane composed of collagen and elastic fibers, the latter
of which provide for some recoil from stretching during
breathing.
Beginning in the main bronchi just proximal to the
lobar bronchi, the bronchial cartilage is organized cir-
cumferentially into haphazard irregular plates that
decrease in size and areal density as the bronchi extend
into the lung (Fig. 2.4; also see Fig. 1.12 in Chapter 1).
With the rapid decrease in the cartilage mass, the circular
smooth muscle bundles become the most prominent
mural components in medium-sized bronchi, and it is
here that bronchoconstriction is most efficient. A few
fibers of longitudinal smooth muscle may be present,
external to the circular smooth muscle. More peripher-
ally, smooth muscle decreases in amount and becomes
scarce in the terminal bronchiole. In chronic obstructive
lung disease, smooth muscle proliferates centrifugally
and can be found prominently even around the orifice of
the alveolar duct. Elastic fibers run longitudinally in the
larger bronchi (Fig. 2.6) and become helical toward the
peripheral airways, like coiled metal springs, and then
continue into the alveolar wall forming integrated fine
networks. The outer limits of the extrapulmonary con-
ducting airways are poorly defined. Alveolar walls form
the outer limit of the intrapulmonary bronchi, bronchi-
oles, and pulmonary arteries.
J.F. Tomashefski, Jr., and c.F. Farver
Bronchial Glands
Mucoserous glands are present in the submucosa of
the trachea and bronchi. These submucosal glands con-
tain both mucous cells and serous cells, both of which
contribute to the secretions of the mucous bilayer cover-
ing the bronchial epithelium (Figs. 2.7 and 2.8). These
mucinous secretions contain bacteriostatic lysozymes
and lactoferrins, antibodies (immunoglobulin A, IgA)
from the surrounding plasma cells, and some antiprote-
ases. In older individuals glandular cells may be largely
replaced by oxyphil cells (oxyphil metaplasia) (Fig. 2.8B).
Approximately one opening of the duct of the bronchial
gland can be found in a I-mm-square area in large
human bronchi. Ciliated cells usually extend into the
duct for a short distance (Fig. 2.8e). The bronchial duct
divides into one or more generations, depending on
the size of the gland, before reaching the glandular acinus.
Myoepithelial cells line the secretory parts of the glands
and are controlled by the autonomic nervous system
(Fig.2.8D).
The volume of the bronchial glands is estimated by
the gland-to-wall ratio (Reid index) or point-counting
methods on random light microscopic sections of a major
bronchus. The Reid index is calculated by measuring the
thickness of the bronchial gland divided by the distance
between the basal lamina of the bronchial mucosa and
the nearest perichondrium (Fig. 2.7B). For this determi-
nation, a well-oriented bronchial cross section of a main-
stem bronchus is necessary, and an average of several
measurements is optimal. For a practical estimation of
the 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 the
percentage of line A divided by line B (see text). (Elastic van Gieson [EVG].)

FIGURE 2.8. Seromucinous glands. A. Seromucinous gland. duct. D. Actin filaments ensheath the mucous gland. (Immuno-
8. Oxyphil metaplasia involving a portion of the glandular histochemical stain for muscle-specific actin.)
lobule (arrow). C. High magnification of a ciliated intercalated
26
In patients without chronic bronchitis the Reid index is
usually ~0.4.!9.20
Mucosa
The tracheal and bronchial mucosa is continuous with the
larynx and consists of a pseudostratified ciliated ~olum­
nar epithelium interspersed with goblet cells that SIt on a
basement membrane. The bronchial basement membrane
is a thin layer of extracellular matrix that provides supp~rt
for the epithelium. By light microscopy the bronchial
basement membrane measures approximately 7 j.tm in
thickness?! The major molecular constituents are colla-
gen IV, fibronectin, laminin-entactin/nidogen complexes,
and proteoglycans.z 1- 23 What appears as a homogeneo~s
basement membrane by light microscopy, however, IS
actually 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 retIcu-
laris is characteristic of bronchial asthma.
The four major types of cells that make up the epithe-
lium are (1) ciliated cells, (2) goblet cells, (3) basal cells,
and (4). ne~roend~crine cells (Fi.g. ~.92!' Layer~d atop .t~e
epithelIum IS the aIrway surface lIqUid that, wIth t~e cIlIa,
comprise the mucociliary escalator that traps foreIgn par-
ticles and organisms that enter the airways and propels
them up and out of the conducting airways via the
larynx. 24
Ciliated Cells
The main function of the ciliated cells of the mucosa is
to propel foreign particles/organisms via the mucociliary
clearance mechanism. The number and importance of
ciliated cells in the air passage are best illustrated by a
scanning electron microscopic view of the surface of t.he
large bronchus, where cilia appear to cover the entIre
FIGURE 2.9. Light microscopic image of the bronchial mucosa
showing the ciliated cells, rare goblet cells, and bronchial basal
cells 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 lummal
surface. The nucleus is basal, and the cytoplasm is rich in
mitochondria, which accumulate apically to supply energy
for cilia (Fig. 2.11). The size of the cell and the length of
the cilia decrease as the diameter of the bronchus
decreases.
A cilium has an intracytoplasmic basal body that is
enmeshed and stabilized in place by a fibrillary network
immediately beneath the cell membrane. From the basal
body a long striated root extends and anchors deep in~o
the cytoplasm, and a basal foot aligns itself sideward m
the direction of the effective stroke of the cilium. At the
neck, or the portion where the cilium emerges from the
cell, the cell membrane forms a rosary-like modification
called the necklace. The cilium tends to break off but also
regenerates itself from this neck portion. The main body
of the cilium is formed by an axoneme surrounded by the
extension of cell membrane. The axoneme consists of a
central 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 CIrcle
of B subfiber. From the A subfiber, two rows of side arms
(the inner and outer dynein arms) protrude to~ard the
B subfiber of the adjacent doublet, and one radIal spoke
extends toward the central pair. The dynein arms are
formed by protein with high adenosine triphosphatase
(ATPase) activity. At the distal e~d of .the c.ilium are
hooking devices or bristles. (A detailed dIscussiOn of the
ultrastructure and pathology of the cilia is provided in
Chapter 5.) . .
The cilia extend into the overlying air surface lIqUid
(ASL), which measures 5 to 100j.tm in thickness. The ASL
is a bilayer of a low-viscosity or watery (sol) lower layer
(a product of the serous and mucous glands in the submu-
cosa), and a high-viscosity or gel ~ppe2~ layer .s~creted
from the goblet cells in the epithelIum. The CIlIa bend
and beat back and forth by sliding opposing groups of
doublets in opposite directions, which is accomplished by
repeated attachments and detachments of dyne~n ~rm~ to
adjacent doublets, similar to the motions used m jackmg
up a car. The recovery stroke of the ciliary beat is believed
to be curved and to occur completely within the watery
(sol) layer of the mucus. The effective stroke is done with
cilia straight up, which allows the bristles to catch and
propel forward the gel or viscous mucus on top of the sol
layer to the larynx where it can be expectorated. The rate
of the ciliary beat is usually 12 to 16 beats/second and
metachronous25 and is coordinated by intercellular gap
junctions that allow for spread of this beat among the
ciliated cells.
Cilia and ciliated cells are constantly exposed and
vulnerable to many noxious agents including cigarette
smoke. Therefore, ultrastructural ciliary changes are
2. Anatomy and Histology of the Lung
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 cili-
ated 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.)
27
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 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 char-
acterized 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 con-
sists of the respiratory bronchiole, alveolar ducts, alveolar
sac, and alveoli (see below). The lung has approximately
30,000 terminal bronchioles, and each drains and concen-
trates the contents of approximately 10,000 alveoli.
FIGURE 2.12. Ciliated cell is the most common cell type in bron-
Membranous bronchioles (including the terminal bron-
chial mucosa. Large goblet cell (G) appears pale. Darkly stained
chiole) are lined completely by epithelial cells. This epi-
basal cell at bottom of mucosa is smaller than other tall colum-
nar cells. Human. TEM, x2500. (Prepared by Dr. N.-S. Wang.) thelium 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
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 con-
tains 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 com-
plete 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
FIGURE 2.13. Multiple mucous granules accumulate near apex
See Chapter 36, Neuroendocrine Carcinomas, for a de- of goblet cell with amorphous and reticular appearance. Human.
tailed discussion of neuroendocrine cells. TEM, xll,OOO. (Prepared by Dr. N.-S. Wang.)
2. Anatomy and Histology of the Lung 29

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 periph-
eral 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 post-
natal growth period, extending from birth until about 10
years of age. Direct epithelial-lined channels between
membranous bronchioles and adjacent alveoli have been FIGURE 2.15. A. Membranous bronchiole with alveolar attach-
termed canals of Lambert (Fig. 2.15C). Depressions and ments. B. Wall of membranous bronchiole. Note single cell layer
eventual fistulous perforations of the wall of small mem- of ciliated epithelium and narrow fascicles of smooth muscle.
branous bronchioles also commonly occur in lung damage, C. Canal of Lambert. Narrow epithelial-lined channel (arrow)
especially in small-airway injury associated with tobacco extends directly into adjacent lung parenchyma from a small
use, leading to peribronchiolar proliferation and exten- 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 reticu-
lum, 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 apopro-
tein 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 dimen-
sion 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 demarcat-
ing 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 intra-
lobular distribution of lesions (see Chapter 24). Inter-
lobular 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 impor-
tance 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 respira-
tory 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 cen-
triacinar and panacinar variants. 32 By virtue of the local-
ization 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 epi-
thelial 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 pro-
gressive 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 recom-
mended 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 bron-
chiolar 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
 32 J.F. Tomashefski, Jr., and c.F. Farver

_LOBULE 1

o LOBULE 2

LOBULE 3

• ATRIA

o DUCTULI ALVEOLARES

• BRONCHIOLI RESPIRATOR II B

• BRONCH IOLI RESPIRATORII A

A • BRONCHIOLUS B

FIGURE 2.19. A. Schematic view of the acinus beginning with membranous bronchiole (A) to branching orders of respiratory
the first respiratory bronchiole branching from a terminal bron- bronchioles and alveolar ducts (B). (A: From Miller,30 with
chiole. Within the acinus can be seen three primary lobules (I, permission. )
II, III). B. Schematic depiction of an acinus from the terminal

FIGURE 2.20. Alveoli. A. Histologic section of several alveoli. like fibers traversing the membrane. Neutrophils are seen in the
B. Alveolus seen en face, stained for elastic tissue. Note thick ill-defined yellow capillary bed in the alveolar membrane.
elastic fibers rimming the alveolar orifice, and delicate thread- (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 alveo-
lar lining cells but cover 90% of the alveolar surface.
A B
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 osmio-
philic lamellar inclusion bodies, the precursors of surfac-
tant (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
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 mem-
brane, 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 hyper-
plastic 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 gly-
coprotein 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 surfac-
tant about the alveolus and its presumed ascending flow
J.F. Tomashefski, Jr. , and c.F. Farver
toward the bronchiole is also helpful in alveolar clear-
ance. 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 col-
lapse 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 cyto-
plasm 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 con-
tinue to move to handle the entire cardiac output. The
combined weight of the two lungs in vivo is approxi-
mately 900 g, of which half consists of blood in the arter-
ies, capillaries, and veins.
Capillary Endothelium
The pulmonary endothelium of the alveolus, which occu-
pies 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 capil-
lary endothelium is similar to that of the capillary endo-
thelium elsewhere in the body. Endothelial cells are
connected to each other by loose junctions, compared to
the tight junctions of alveolar epithelial cells, and there-
fore more readily allow the passage of fluids and macro-
molecules into the interstitial compartment. 35 .36
2. Anatomy and Histology of the Lung
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 angio-
tensin I to angiotensin II and the inactivation of brady-
kinin 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 pros-
taglandins, and previously accumulated drugs and metab-
olites. 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 polyg-
onal. 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 cap-
illaries, 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-
35
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 bronchovascu-
lar 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 macro-
phages are present in small numbers in the alveolar wall
and bronchial interstitial space. Neutrophils are most fre-
quently 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 epi-
thelial cells. When stimulated, they contract to distort and
disrupt the capillary flow. The detailed control mechanisms,
the mediators that induce their contraction, and the physi-
ologic 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 hyperinfla-
tion 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 alveo-
lar 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 golden-
brown 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 differenti-
ated cells of the myeloid lineage. They are derived from
bone marrow stem cells as monoblastic myeloid progeni-
tors.39 In the presence of granulocyte-macrophage colony-
stimulating 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 environ-
ment, they become either activated as nonspecific imma-
ture 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. In-
creases 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) prolif-
eration of the local resident population of interstitial
macrophages that divide and move into the alveolar
space where they terminally differentiate into AMs fol-
lowed 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 sec-
ondary lysosomes (Fig. 2.25). The macrophages move
microvilli, nucleus (N) and abundant cytoplasmic dense bodies
containing lysosomes and phagolysosomes. Some of these het-
erogeneous cytoplasmic inclusions contain lipid from metabo-
lized 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 exoge-
nous and endogenous tissues and debris. Once in the air
space, and especially after engulfing all the debris, mac-
rophages probably do not migrate through the intact
alveolar or bronchial epithelial layer back into the inter-
stitium. Intravascular macrophages are rare in human
lungs, and probably represent intravascular and submu-
cosal clearance of noxious agents following the break-
down 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 Prus-
sian 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 sys-
temic mucosa-associated lymphoid tissue (MALT) (e.g.,
Peyer's patches, appendiceal lymphoid tissue ).44 The lym-
phoid 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 asso-
ciated 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 secre-
tory 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-associ-
ated lymphoid tissue probably represents the site of local
antibody production in response to antigen challenge
from the airway.
Bronchus-associated lymphoid tissue has been identi-
fied 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 lymphoprolifera-
tive disease. )46
37
The Vasculature of the Lung
The lung has a dual blood supply: the pulmonary circula-
tion and the bronchial (nutritional) circulation. The
former is a low-pressure/high-capacity system that
accommodates total systemic venous return and is struc-
turally 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, deliv-
ers 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 arter-
ies, which further divide into lobar arteries before enter-
ing the lung. As it enters the pulmonary hilum, the
pulmonary artery is situated superiorly and slightly ante-
riorly 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. 6The 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 arter-
ies 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 con-
sisting 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 pulmo-
nary 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 pulmo-
nary artery. Note interrupted pattern of elastic fibers. B. Mus-
cular 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 nonmus-
cular 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 irregu-
larly 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 well-
defined external elastic lamina (arterialization) (see
Chapter 28). The small venules and lobular veins con-
verge 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
Muscular Partially Nonmuscular
muscular
Capillary
Cross
section
o o o
FIGURE 2.27. Schema of distribution of muscle in intraparen-
chymal 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, pulmo-
nary 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 bronchi-
ectasis and pulmonary hypertension, the bronchial arter-
ies 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 con-
trast 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 hemi-
azygous veins into the right atrium.! Histologically, bron-
chial 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 bron-
chial and pulmonary capillaries and small veins. Preca-
pillary bronchopulmonary anastomoses have been docu-
mented 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 bronchopul-
monary anastomoses in fetal and neonatal lungs, Wagen-
voort and Wagenvoort49 also encountered bronchopul-
monary 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). Bron-
chopulmonary 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 bronchopulmo-
nary arteries has not been well established.
In adult lungs, P ump55 documented numerous precapil-
lary anastomoses between bronchial and pulmonary
arteries using vascular injection and cast techniques. In
earlier studies by von Hayek and Lapp, precapillary anas-
tomotic vessels called sperrarterien were thought to act
as muscular sphincters that regulated flow between the
bronchial and pulmonary circuits. 56 Occasional thick-
walled, 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 prolifera-
tion, 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 pulmo-
nary hypertension or proximal pulmonary artery obstruc-
tion (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
• thelial cells with few organelles. 59 Although all types of
..
• lymphangitis carcinomatosa, however, lymphatic chan-
FIGURE 2.28. Hypermuscular artery in interlobular septum,
probably representing a bronchopulmonary anastomosis (Sper-
rarterien) (EVG).
the outer parts of the lung via the visceral pleural lym-
phatics, 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 bron-
chiole. 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 endo-
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 visu-
alize histologically. In conditions of pulmonary edema or
nels 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 lympha-
tic duct is an inconstant channel that may consist of mul-
tiple fine branches that empty separately into the right
jugular, subclavian, or innominate veins. 1 Because of
the intermixture of lymph flow in the interconnect-
ing 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) sub-
carinallymph nodes located posterior to the main bron-
chial 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 paren-
chyma. 6 Lymph node sampling is important in the staging
of lung cancer, and the major lymph node anatomic sta-
tions are illustrated in Chapter 35 (Fig. 35.18). Intrapul-
monary 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 exten-
sive 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 car-
cinomatosa 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 vas- Nerves
cular spread of tumor to the lung followed by invasion of
juxtavascular lymphatics, and antegrade spread to the The lung is innervated via the autonomic nervous system.
bronchial lymph nodes is the major pathway of lymphatic Nerve trunks enter the lung at the hilum and are ar-
permeation (see Chapter 44).61 ranged in two plexuses: periarterial and peribronchial.
Typically, bronchopulmonary lymph nodes in adults The peribronchial plexus is further divided into an extra-
contain a variable degree of fine black pigment and chondral and subchondral plexus according to its location
grossly appear black or mottled black-gray. In situations relative to the bronchial cartilages. 6s .66 The peribronchial
of occupational dust exposure, increased pigment, along plexus contains both myelinated and unmyelinated fibers,
with silica and other dusts, may induce nodal fibrosis or while the periarterial plexus contains only unmyelinated
silicotic nodules prior to the development of pulmonary fibers. 6s Ganglia are located mainly in the extrachondral
pneumoconiosis (see Chapter 26),62 Ferruginous bodies plexus to the level of the distal bronchi (Fig. 2.31). Nerve
may also be identified in lymph nodes following heavy
inhalational exposure to asbestos (see Chapter 27).63.64
Lymph node follicular hyperplasia and sinus histiocy-
tosis may be a cause of lymphadenopathy in bronchopul-
monary lymph nodes as in other sites. Sinus histiocytosis
at times has a nodular appearance simulating nonne-
crotizing granulomas (Fig. 2.30A). In cases of chronic
bronchopulmonary infection, such as cystic fibrosis, eryth-
rophagocytosis 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 histo- ... ,
plasma 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-Wesen- I,
berg bodies, but are deep brown and stain intensely for
iron. A variety of infectious and noninfectious granulo-
-.
matous diseases target the pulmonary and mediastinal
lymph nodes, which may harbor fibrotic nodules and/or FIGURE 2.31. Neural ganglion is seen in the extra chondral
fibrocaseous granulomas as the residua of the prior infec- plexus adjacent to bronchial artery and fibroelastic tissue of the
tion (see Chapters 9 and 10). 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 effer-
ent (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 Acetyl-
choline 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 neu-
rotransmitters in the NANC pathway are vasoactive
intestinal peptide (VIP) and nitric oxide (NO).67
FIGURE 2.32. Terminal portion of nerve with small empty vesi-
cles and mitochondria representing afferent cholinergic nerve
ending (in alveolar wall [arrow». Human. TEM, x45,OOO. (Pre-
pared 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 fibers 67 ; SARs are responsible
for the Hering-Breuer reflex that inhibits further inspira-
tion 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 acti-
vated by chemical and mechanical irritants. Their stimula-
tion 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 bron-
choconstriction, mucous hypersecretion, and cough. C
fibers are especially sensitive to capsaicin, a pungent com-
ponent 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 com-
pletely 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 inter-
lobar fissures, and the parietal pleura, which covers the
inner surface of the thoracic cage, mediastinum, and dia-
phragm. The visceral pleura reflects at the hilum and
pulmonary ligament to continue as the parietal pleura.
The apposing two layers of mesothelial cells are sepa-
rated 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 costo-
phrenic 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 43

Epithelium

Mucous gland

Smooth muscle

Blood vessel

/
I
,
\
Bronchus

Bronchial ganglion

Dorsal root ganglion

V3gUS nerve

Thoracic segment Thoracic and cervical

ganglia
I of spinal cord
Inferior g3ngl ion •

Afferent (sensory)

Superior ganglion
Sympatheti c efferent

P3'3symp3thetic
efferent

Medu lla 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 pene-
trate the two apposing layers of parietal pleura simulta-
neously and enter the liver or other abdominal organs.
The blood supply to the visceral pleura is from the bron-
chial arterial system. 50
The gross appearance of the pleura is that of a smooth,
glistening, and semitransparent membrane. The macro-
scopic 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 submesothe-
lial 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 overly-
ing 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 paren-
chyma 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 substruc-
ture 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, mitochon-
dria, 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 gov-
erned 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 sepa-
rated 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 anom-
alies 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 costo-
vertebral 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. Expi-
ration in quiet breathing is a passive relaxation of inspira-
tory 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 arter-
ies 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 bound-
ary 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 esopha-
gus 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 ver-
tebra. 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 contrac-
tion, the diaphragm flattens, increasing the volume of the
thoracic cavity. Fraser and Pare l found the mean excur-
sion 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, pulmo-
nary fibrosis, or surgical lung excision.
The mediastinum traditionally is separated into supe-
rior, 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: lympho-
mas 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 con-
tribution 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 edi-
tions 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 Brit-
tingham Memorial Library at MetroHealth Medical
Center.
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