Respiratory Epithelium

• Pseudostratified columnar epithelium

• This epithelium has at least five cell types, all of which touch the thick
basement membrane:

• Ciliated columnar cells are the most abundant, each with about 300
cilia on its apical surface
• Goblet cells are also abundant in some areas of the respiratory
epithelium filled in their apical portions with granules of mucin
glycoproteins
 Respiratory Epithelium
• Brush cells are a much more sparsely scattered and less easily found,
columnar cell type, which has a small apical surface bearing a tuft of
many short, blunt microvilli
• Brush cells express some signal transduction components like those of
gustatory cells and have afferent nerve endings on their basal surfaces
and are considered to be chemosensory receptors
• Small granule cells are also difficult to distinguish in routine
preparations, but possess numerous dense core granules 100–300 nm in
diameter. Like brush cells, they represent about 3% of the total cells and
are part of the diffuse neuroendocrine system
• Basal cells, small rounded cells on the basement membrane and not
extending to the luminal surface, are stem cells that give rise to the
other cell types.
 Olfaction
• The olfactory chemoreceptors are located in the olfactory epithelium, a
specialized region of the mucous membrane covering the superior conchae
at the roof of the nasal cavity
• In humans, it is about 10 cm2 in area and up to 100 m in thickness. It is a
pseudostratified columnar epithelium composed of three types of cells
• Basal cells are small, spherical or cone-shaped and form a layer at the basal
lamina. They are the stem cells for the other two types.
• Supporting cells are columnar, with broad, cylindrical apexes and narrower
bases. On their free surface are microvilli submerged in a fluid layer. Well-
developed junctional complexes bind the supporting cells to the adjacent
olfactory cells
 Olfaction
• Olfactory neurons are bipolar neurons present throughout this
epithelium. They are distinguished from supporting cells by the
position of their nuclei, which lie between those of the supporting
cells and the basal cells.
 Paranasal sinuses
• The paranasal sinuses are bilateral cavities in the frontal, maxillary,
ethmoid, and sphenoid bones of the skull
• They are lined with a thinner respiratory epithelium with fewer goblet
cells
• The lamina propria contains only a few small glands and is continuous
with the underlying periosteum
• The paranasal sinuses communicate with the nasal cavities through
small openings and mucus produced in the sinuses is moved into the
nasal passages by the activity of the ciliated epithelial cells.
 Epiglottis
• The epiglottis, which projects from the upper rim of the larynx,
extends into the pharynx and has lingual and laryngeal surfaces
• The entire lingual surface and the apical portion of the laryngeal
surface are covered with stratified squamous epithelium
• At variable points on the laryngeal surface of the epiglottis the
epithelium undergoes a transition to ciliated pseudostratified
columnar epithelium
• Mixed mucous and serous glands are found in the lamina propria
beneath the epithelium.
 Trachea

• The trachea is 12-14 cm long and lined with a typical respiratory

mucosa
• In the lamina propria numerous seromucous glands produce watery
mucus and in the submucosa 16–20 C-shaped rings of hyaline
cartilage keep the tracheal lumen open
• The open ends of the cartilage rings are on the posterior surface,
against the esophagus, and are bridged by a bundle of smooth muscle
(trachealis muscle) and a sheet of fibroelastic tissue attached to the
perichondrium.
• The entire organ is surrounded by adventitia.
 Bronchial Tree & Lung
• The trachea divides into two primary bronchi that enter the lungs at
the hilum, along with arteries, veins, and lymphatic vessels. After
entering the lungs, the primary bronchi course downward and
outward, giving rise to three secondary (lobar) bronchi in the right
lung and two in the left lung, each of which supplies a pulmonary
lobe. These lobar bronchi again divide, forming tertiary (segmental)
bronchi. Each of these tertiary bronchi, together with the smaller
branches it supplies, constitutes a bronchopulmonary segment
• The tertiary bronchi give rise to smaller and smaller bronchi, whose
terminal branches are called bronchioles. Each bronchiole enters a
pulmonary lobule, where it branches to form five to seven terminal
bronchioles
Bronchi
• Each primary bronchus branches repeatedly, with each branch becoming
progressively smaller until it reaches a diameter of about 5 mm. The mucosa
of the larger bronchi is structurally similar to the tracheal mucosa except for
the organization of cartilage and smooth muscle (Figure 17–7). In the primary
bronchi most cartilage rings completely encircle the lumen, but as the
bronchial diameter decreases, cartilage rings are gradually replaced with
isolated plates of hyaline cartilage. Abundant mucous and serous glands are
also present, with ducts opening into the bronchial lumen. In the bronchial
lamina propria is a layer of crisscrossing bundles of spirally arranged smooth
muscle (Figures 17–7 and 17–8), which become more prominent in the smaller
bronchial branches. Contraction of this muscle layer is responsible for the
folded appearance of the bronchial mucosa observed in histologic section.
• The lamina propria also contains elastic fibers and abundant mucous
and serous glands (Figure 17–8) whose ducts open into the bronchial
lumen. Numerous lymphocytes are found both within the lamina
propria and among the epithelial cells. Lymphatic nodules are present
and are particularly numerous at the branching points of the
bronchial tree. Elastic fibers, smooth muscle, and MALT become
relatively more abundant as bronchi become smaller and cartilage
and other connective tissue are reduced.
EPITHELIUM (E)
LAMINA PROPRIA(LP)
SMOOTH MUSCLE (SM)
CARTILAGE (C)
BLOOD VESSELS (V)
NERVES (N)
LUNG TISSUE (LT)
 Bronchioles
• Bronchial branches less than
about 5 mm in diameter lack
supporting cartilage and are
called bronchioles. (a): A large
bronchiole has the
characteristically folded
respiratory epithelium (E) and
prominent smooth muscle
(arrows), but is supported only
by fibrous connective tissue
(C) with no glands
Terminal
bronchiole and
Clara cells
• The last parts of the air
conducting system before the
sites of gas exchange appear are
called the terminal bronchioles,
which generally have diameters
of one to two mm. (a): Cross-
section shows that a terminal
bronchiole has only one or two
layers of smooth muscle cells.
The epithelium contains ciliated
cuboidal cells and many low
columnar nonciliated cells
 Clara cells
• The nonciliated Clara cells with bulging domes of apical cytoplasm
contain granules, as seen better in a plastic section.

• Named for Dr. Max Clara, the histologist who first described them in
1937, these cells have several important functions.
• They secrete components of surfactant which reduces surface tension
and helps prevent collapse of the bronchioles. In addition, Clara cells
produce enzymes that help break down mucus locally
 Respiratory Bronchioles
• Respiratory Bronchioles
• Each terminal bronchiole subdivides into two or more
respiratory bronchioles that serve as regions of
transition between the conducting and respiratory
portions of the respiratory system

• The respiratory bronchiolar mucosa is structurally

identical to that of the terminal bronchioles, except
that their walls are interrupted by the openings to
saclike alveoli where gas exchange occurs
Alveolar Ducts
• Both the alveolar ducts and the alveoli are lined with extremely
attenuated squamous alveolar cells.
• In the lamina propria surrounding the rim of the alveoli is a thin
network of smooth muscle cells, which disappears at the distal ends
of alveolar ducts.
• A rich matrix of elastic and collagen fibers provides the only support
of the duct and its alveoli.
Respiratory bronchioles, alveolar ducts, and
alveoli.
• Lung tissue has a spongy structure because of the abundant air passages and
pockets called alveoli. (a): Typical section of lung tissue including many
bronchioles, some of which are respiratory bronchioles (RB) cut lengthwise, and
showing the branching continuity with alveolar ducts (AD) and sacs (AS).
Respiratory bronchioles still have a layer of smooth muscle and some regions of
cuboidal epithelium, but alveolar ducts have only sparse strands of smooth
muscle and an epithelium consisting of only a series of neighboring alveoli. The
smooth muscle fibers are sphincter-like and appear as knobs between adjacent
alveoli. Individual alveoli (A) all open to the sacs or ducts. The respiratory
bronchiole runs along a thin-walled branch of the pulmonary artery (PA), which
has a relatively thin wall, while branches of the pulmonary vein (V) course
elsewhere in the parenchyma.
• Higher magnification
shows the relationship
of the many rounded,
thin-walled alveoli (A) to
alveolar ducts (AD).
Alveolar ducts end in
two or more clusters of
alveoli called alveolar
sacs (AS). Those alveoli
shown here that do not
show openings to the
ducts or the sacs have
their connections in
adjacent planes of other
sections
 Alveoli
Alveoli are saclike evaginations (about 200 m in diameter) of the respiratory
bronchioles, alveolar ducts, and alveolar sacs
. Structurally, alveoli resemble small pockets that are open on one side, similar to
the honeycombs of a beehive
. The structure of alveolar walls is specialized to enhance diffusion between the
external and internal environments. Generally, each wall lies between two
neighboring alveoli and is therefore called an interalveolar septum.
These septa contain the cells and ECM of connective tissue, notably the elastic and
collagen fibers, which is vascularized with the richest capillary network in the
body Air in the alveoli is separated from capillary blood by three components
referred to collectively as the respiratory membrane or blood-air barrier:
• Surface lining and cytoplasm of the alveolar cells,
• Fused basal laminae of the closely apposed alveolar cells and capillary
endothelial cells, and
• Cytoplasm of the endothelial cells
• Capillary endothelial cells are extremely thin and can be easily confused with
type I alveolar epithelial cells
• Type I alveolar cells (also called type I pneumocytes or squamous alveolar cells)
are extremely attenuated cells that line the alveolar surfaces. Type I cells cover
97% of the alveolar surface (type II cells covering the remainder).
• Type II alveolar cells (type II pneumocytes) are interspersed among the type I
alveolar cells with which they have occluding and desmosomal junctions
• The lamellar bodies give rise to a material that spreads over the alveolar surfaces
as the pulmonary surfactant, providing an extracellular coating that lowers
surface tension.
MEDICAL APPLICATION
• Respiratory distress syndrome (RDS)
• Alveolar macrophages
• In congestive heart failure, the lungs become congested with blood,
and erythrocytes pass into the alveoli, where they are phagocytized
by alveolar macrophages. In such cases, these macrophages are
called heart failure cells
Regeneration in the Alveolar Lining
• Inhalation of toxic gases or similar materials can kill type I and type II cells lining
pulmonary alveoli. Death of the first cells results in increased mitotic activity in
the remaining type II cells, the progeny of which become both cell types. The
normal turnover rate of type II cells is estimated to be 1% per day and results in a
continuous renewal of both alveolar cells. With increased toxic stress Clara cells
can also divide and give rise to alveolar cells.

• Squamous cell carcinoma, the principal lung tumor type, usually results from the
effects of cigarette smoking on the bronchial and bronchiolar epithelial lining.
Chronic smoking induces the transformation of the respiratory epithelium into a
stratified squamous epithelium, an initial step in its eventual differentiation into
a tumor.