• The respiratory system includes the lungs and a series of

airways that connect the lungs to the external

environment.

• The respiratory system can be functionally classified into

two major subdivisions: a conducting portion, consisting
of airways that deliver air to the lungs, and a respiratory
portion, consisting of structures within the lungs in
which oxygen in the inspired air is exchanged for carbon
dioxide in the blood.
A. Nasal Cavity. The nasal cavity is subdivided by the median nasal septum into right and
left nasal cavities, each leading to the paranasal sinuses, thus providing a large surface area
for filtering, moistening, and warming the inspired air.

A.1. The nares are the nostrils; their outer portions are lined by thin skin. They open into the vestibule.
A. 2. The vestibule is the first portion of the nasal cavity, where the epithelial lining becomes nonkeratinized.
Posteriorly, the lining changes to the respiratory epithelium (pseudostratified ciliated columnar epithelium
with goblet cells).

a. The vestibule contains vibrissae (thick, short hairs), which filter large particles from the inspired air.
b. It has a richly vascularized lamina propria (many venous plexuses) and contains seromucous glands.
c. Each nasal cavity contains bony shelves that originate from the lateral nasal wall and project into the nasal
cavity. These are the superior, middle, and inferior conchae (turbinate bones). Their structure and placement
within the nasal cavity divide it into separate regions, thereby introducing turbulence to the airflow. Since they
are covered by respiratory epithelium, their presence increases the surface area for warming, filtering, and
moistening the inspired air.
d. Paranasal sinuses are air-filled, hollowed-out portions of the sphenoid, frontal, ethmoid, and maxillary
bones. These air sinuses are lined by a thin respiratory epithelium, but the function of the paranasal sinuses is
not known.
A. 3. Olfactory epithelium

• The olfactory epithelium is located in the roof of the nasal cavity, on either
side of the nasal septum, and the superior nasal conchae.
• It is a tall, pseudostratified columnar epithelium consisting of olfactory
cells, supporting (sustentacular) cells, and basal cells (stem cells).
• It has a lamina propria that contains many veins and unmyelinated
nerves, and houses Bowman glands.
A.3.1 Olfactory cells are bipolar nerve cells characterized by a bulbous apical projection
(olfactory vesicle) from which several modified cilia extend.

A.3.1.a. Olfactory cilia(olfactory hairs)

• are very long, nonmotile cilia that extend over the surface of the olfactory epithelium.
• act as a receptor for odor.

A.3.1.b. Supporting (sustentacular) cells

• possess nuclei that are more apically located than those of the other two cell types.
• have many microvilli and a prominent terminal web of filaments.
• help maintain a microenvironment conducive to olfactory function and survival.
A.3.1.c. Basal cells
• rest on the basal lamina but do not extend to the surface.
• are believed to be regenerative for all three cell types.
• Replaces olfactory neurons every 2-3 months and support cells less frequently

A.3.1.d. Bowman glands/Olfactory glands

• produce a thin, watery secretion that is released onto the olfactory epithelial surface via
narrow ducts.
• Odorous substances dissolved in this watery material are detected by the olfactory cilia.
The secretion also flushes the epithelial surface, preparing the receptors to receive new
odorous stimuli.
B. Nasopharynx

• The nasopharynx, the posterior continuation of the nasal cavities, becomes

continuous with the oropharynx at the level of the soft palate.
• It is lined by respiratory epithelium, whereas the oropharynx and
laryngopharynx are lined by stratified squamous nonkeratinized epithelium.
• The lamina propria of the nasopharynx, located beneath the respiratory
epithelium, contains mucous and serous glands as well as an abundance of
lymphoid tissue known as the Waldeyer ring, including the pharyngeal tonsil.
When the pharyngeal tonsil is inflamed, it is called an adenoid.
• Opening into the right and left lateral walls of the nasopharynx are the auditory
tubes (Eustachian tubes), each arising from its respective middle ear cavity.
C. Larynx
• The larynx connects the pharynx with the trachea. It functions to produce sounds and
close the air passage during swallowing.
• The wall of the larynx is supported by hyaline cartilages (thyroid, cricoid, and lower part of
arytenoids) and elastic cartilages (epiglottis, corniculate, and tips of arytenoids).
• The laryngeal wall also possesses skeletal muscle, connective tissue, and glands.

C.1. The vocal cords (vocal folds) consist of skeletal muscle (the vocalis muscle), the vocal
ligament (formed by a band of elastic fibers), and a covering of stratified squamous
nonkeratinized epithelium.
• Contraction of the laryngeal muscles changes the size of the opening between the vocal
cords, which affects the pitch of the sounds caused by air passing through the larynx.
• Inferior to the vocal cords, the lining epithelium changes to respiratory epithelium, which
lines air passages down through the trachea and intrapulmonary bronchi.

C.2. Vestibular folds (false vocal cords) lie superior to the vocal cords.
• These folds of loose connective tissue contain glands, lymphoid aggregations, and fat cells.
• They are covered by stratified squamous nonkeratinized epithelium.
D. Trachea and extrapulmonary (primary) bronchi

• The trachea, the largest conducting section of the respiratory system, bifurcates into the
right and left primary bronchi, each of which enters the hilum of the lung on its side.

• The walls of these structures are supported by C-shaped hyaline cartilages (C-rings), whose
open ends face posteriorly. Smooth muscle (trachealis muscle in the trachea) extends
between the open ends of these cartilages.

• Dense fibroelastic connective tissue is located between adjacent C-rings, permitting

elongation of the trachea during inhalation.
D.1. Mucosa
• The basement membrane is a very thick layer underlying the epithelium.
• The lamina propria is a thin layer of connective tissue that lies beneath the basement
membrane. It contains longitudinal elastic fibers separating the lamina propria from the
submucosa.
• The respiratory epithelium in the trachea possesses the following cell types.

D.1.1. Ciliated cells

• have long, actively motile cilia that beat toward the mouth.
• move inhaled particulate matter trapped in mucus toward the oropharynx, thus
protecting the delicate lung tissue from damage.
• also possess microvilli.

D.1.2. Mature goblet cells

• goblet-shaped and are filled with large secretory granules, containing mucinogen droplets,
which are secreted onto the epithelial surface to trap inhaled particles.
• Secrete mucus
D.1.3. Small granule-mucous cells(brush cells)
• contain varying numbers of small mucous granules.
• are sometimes called brush cells because of their many uniform microvilli.
• actively divide and often replace recently desquamated cells.
• may represent goblet cells after they have secreted their mucinogen.

D.1.4. Diffuse neuroendocrine cells

• are also known as small granule cells, amine precursor uptake and decarboxylation (APUD
cells), or enteroendocrine cells.
• contain many small granules concentrated in their basal cytoplasm.
• synthesize different polypeptide hormones and serotonin, which often exert a local effect on
nearby cells and structures (paracrine regulation). The peptide hormones may also enter the
bloodstream and have an endocrine effect on distant cells and structures.
D.1. 5. Basal cells

• are short cells that rest on the basal lamina, but do not extend to the lumen; thus, this
epithelium is pseudostratified.
• are stem cells that are able to divide and replace the other cell types.

D.2. The submucosa is a connective tissue layer containing many seromucous glands
(produces watery mucus).

D.3. The adventitia contains C-shaped hyaline cartilages and forms the outermost layer of the
trachea.
E. Intrapulmonary bronchi (Secondary bronchi)
• Intrapulmonary bronchi arise from subdivisions of the primary
bronchi upon entering the hilum of the lung. It is at this level that the
cartilaginous rings of the bronchi are replaced with plates of
irregularly shaped hyaline cartilage.
• They divide many times and give rise to lobar and segmental bronchi.
• They are lined by respiratory epithelium.
• Spiraling smooth muscle bundles separate the lamina propria from
the submucosa, which contains seromucous glands.
 E. Intrapulmonary bronchi (Secondary bronchi)

E – Pseudostratified ciliated
columnar epithelium with goblet
cells
SM – Smooth muscle cells
C – irregular plates of cartilage
G – Seromucous glands
L – lymphoid tissue
A- Alveoli
F. Primary and Terminal bronchioles

Primary bronchioles
• Primary bronchioles have a diameter of 1mm or less.
• They are lined by epithelium that varies from ciliated columnar with goblet cells in the larger airways to ciliated cuboidal with
Clara cells in the smaller passages.
• They divide to form several terminal bronchioles after entering the pulmonary lobules.

Terminal bronchioles
• Terminal bronchioles are the most distal part of the conducting portion of the respiratory system.
• They have a diameter of less than 0.5mm.
• They are lined by a simple cuboidal epithelium that contains mostly club cells (formerly known as Clara cells), some ciliated
cells, and no goblet cells.
• Club cells have the following functions:
(1) Club cells divide, and some of them differentiate to form ciliated and non-ciliated cells.
(2) They secrete a surfactant-like material that reduces alveolar surface tension, preventing the collapse of alveoli. They
also produce club cell secretory protein whose function is assumed to be the protection of the respiratory epithelium.
(3) They metabolize airborne toxins, a process that is carried out by cytochrome P450 enzymes in their abundant smooth
endoplasmic reticulum (SER).
F. Primary and Terminal bronchioles

Cross section of a bronchiole

E – simple columnar epithelium
SM – smooth muscle cells
MA – Muscular artery
This portion of the respiratory system
includes the respiratory bronchioles,
alveolar ducts, alveolar sacs, and alveoli, all
in the lung. The exchange of gases takes
place in this portion of the respiratory
system.
• The respiratory bronchioles mark the transition from the conducting to the
respiratory portion of the respiratory system.
• They are lined by a simple cuboidal epithelium that contains mostly club cells and
some ciliated cells, except where their walls are interrupted by alveoli, the sites
where gas exchange occurs and where the lining abruptly changes to a simple
epithelium composed of highly attenuated squamous cells.
Electron micrograph of
respiratory bronchiole

CL – Clara cells
C – Ciliated cells
M – Smooth muscle cells
E – Elastic tissue
V - venules
Arrowheads – capillaries
A – Alveoli
P1 – Type 1 Pneumocytes
• Alveolar ducts are linear passageways continuous with the respiratory bronchioles.
• Their walls consist of adjacent alveoli, which are separated from one another only by an
interalveolar septum.
• They are the most distal portion of the respiratory system to contain smooth muscle cells,
which rim the openings of adjacent alveoli and which often appear as knobs in
histological sections.
• Alveolar ducts are lined by type II pneumocytes and the highly attenuated simple
squamous epithelium of type I pneumocytes.
AD – Alveolar duct
AS - Alveolar sac
Arrow – smooth muscle cells
A - alveoli
are expanded outpouchings of numerous alveoli at the distal ends of alveolar ducts.
• Alveoli are pouch-like evaginations about 200 um in diameter in the walls of respiratory
bronchioles, in alveolar ducts, and in alveolar sacs.
• They have thin walls, across which oxygen and carbon dioxide diffuse between the air and
the blood.
• They are separated from each other by interalveolar septa that may contain one or more
alveolar pores (pores of Kohn). These pores permit equalization of pressure between alveoli.
• They are rimmed by elastic fibers at their openings (except in alveolar ducts, where they are
rimmed by smooth muscle cells) and are supported by many reticular fibers in their walls.
• They are lined by a highly attenuated simple squamous epithelium composed of type I and
type II pneumocytes.
D.2.1. Type I pneumocytes (type I alveolar cells)

• cover about 95% of the alveolar surface and form part of the blood-gas barrier where the
exchange of oxygen and carbon dioxide occurs.
• have an extremely thin cytoplasm that maybe less than 80nm thick
• form tight junctions with adjacent cells.
• may have phagocytic capabilities.
• are not able to divide.
1. D.2.2. Type II pneumocytes (type II alveolar cells; great alveolar cells;
granular pneumocytes; septal cells)
• are cuboidal and are most often found near septal intersections.
• bulge into the alveolus and have a free surface that contains short microvilli around
their peripheral borders.
• are able to divide and regenerate both types of alveolar pneumocytes.
• form tight junctions with adjacent cells.
• synthesize pulmonary surfactant, which is stored in cytoplasmic lamellar bodies.
1. D.2.2. Type II pneumocytes (type II alveolar cells; great alveolar cells;
granular pneumocytes; septal cells)

LB – Lamellar bodies
D.2.3. Alveolar macrophages (alveolar phagocytes; dust cells)

• are the principal mononuclear phagocytes of the alveolar surface.

• remove inhaled dust, bacteria, and other particulate matter trapped in the
pulmonary surfactant, thus providing a vital line of defense in the lungs.
• migrate to the bronchioles after filling with debris. From there, they are carried
via ciliary action to the upper airways, eventually reaching the oropharynx,
where they are either swallowed or expectorated.
• may also exit by migrating into the interstitium and leaving via lymphatic
vessels.
• The interalveolar septum is the wall, or partition, between two
adjacent alveoli.
• It is bounded on its outer surfaces by the extremely thin,
simple, squamous epithelium lining the alveoli.
• It contains many elastic and reticular fibers in its thicker
regions.
• It houses continuous capillaries in its central (interior) region.
Electron micrograph showing the blood-gas barrier in the lung
A – Alveolus
RBC – erythrocyte
P1 – Type 1 pneumocyte
BL – Basal laminae
E – Endothelial cell
• Lung lobules vary greatly in size and shape, but each has an

apex directed toward the pulmonary hilum and a wider base

directed outward.

• Each lobule contains a single primary bronchiole, which

enters at the apex and branches to form five to seven

terminal bronchioles. The terminal bronchioles in turn divide,

ultimately giving rise to alveoli at the base of the lobule.

A. Pulmonary Artery
• The pulmonary artery carries blood to the lungs to be oxygenated.
• It enters the root of each lung and extends branches along the divisions of the bronchial tree.
• It enters the lung lobules, where its branches follow the bronchioles.
B. Pulmonary veins
• In lung lobules, pulmonary veins run in the intersegmental connective tissue, separated from
the arteries.
• After leaving the lobules, the pulmonary veins come close to divisions of the bronchial tree
and run parallel to branches of the pulmonary artery as they accompany bronchi to the root
of the lung.
C. Bronchial arteries and veins
• Bronchial arteries and veins provide nutrients and remove wastes from the nonrespiratory
portions of the lung (bronchi, bronchioles, interstitium, and pleura).
• They follow the branching pattern of the bronchial tree and form anastomoses with the
pulmonary vessels near capillary beds.
The pulmonary nerve supply consists primarily of autonomic
fibers to the smooth muscle of the bronchi and bronchioles.
Axons are also present in the thicker parts of the interalveolar
septa.
1. Parasympathetic stimulation causes contraction of
pulmonary smooth muscle.
2.Sympathetic stimulation causes relaxation of pulmonary
smooth muscle and can be mimicked by certain drugs that
cause dilation of bronchi and bronchioles.