Module 15

Histology of the Respiratory System

Desired Learning Outcomes

The students are expected to:

1. Reflect on the relevance of respiratory system in the animal body.
2. Outline the morphology of the tissues and organs comprising the respiratory system.
3. Discuss how tissues and organs comprising the respiratory system perform their roles
synergistically in the body of animals.
4. Perform the activities in the module.
The respiratory system is constantly filtering through the external environment as animals
breathe air. The airways must maintain the ability to clear inhaled pathogens, allergens, and debris
to maintain homeostasis and prevent inflammation.
The respiratory system subdivides into a conducting portion and a respiratory portion. The
majority of the respiratory tree, from the nasal cavity to the bronchi, is lined by pseudostratified
columnar ciliated epithelium. The bronchioles are lined by simple columnar to the cuboidal
epithelium, and the alveoli possess a lining of thin squamous epithelium that allows for gas
exchange.
The Conducting Portion
The conducting piece of the respiratory system consists of the nasal cavity, trachea,
bronchi, and bronchioles. The luminal surfaces of this entire portion have a lining of ciliated
pseudostratified columnar epithelium and contain goblet cells. Their role is to secrete mucus that
serves as the first line of defense against incoming environmental pathogens. Cilia move the
mucus-bound particulate up and away for expulsion from the body. The various types and
abundance of cells are dependent on which region of the airway they are.
In the most proximal airway, hyaline cartilage rings support the larger respiratory passages,
namely, the trachea and bronchi, to facilitate the passage of air. Three major cell types are found
in this region: ciliated, non-ciliated secretory cells, and basal cells.
Ciliated cells, each lined with 200 to 300 cilia, account for more than half of all epithelial
cells in the conducting airway. As the degree of branching within the airway tree continues, the
epithelium gradually changes from pseudostratified to simple cuboidal; and the predominant cells
become non-ciliated cells, Clara cells.

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 Figure 15A. Outline of the Conducting Portion

The Gas-Exchange Portion

The respiratory or gas-exchange region of the lung is composed of millions of alveoli,
which are lined by an extremely thin, simple squamous epithelium that allows for the easy
diffusion of oxygen and carbon dioxide. Additionally, cuboidal, surfactant-secreting cells, Type II
pneumocytes, are also found lining the walls of alveoli. Surfactant, which is primarily composed
of dipalmitoyl phosphatidylcholine, has a vital role in lowering the surface tension of water to
allow for effective gas exchange.
Type I pneumocytes are flattened cells that create a very thin diffusion barrier for gases.
Tight junctions are found connecting one cell to another. The principal functions of Type I
pneumocytes are gas exchange and fluid transport. Type II Pneumocytes secrete surfactant, which
decreases the surface area between thin alveolar walls, and stops alveoli from collapsing during
exhalation. These cells connect to the epithelium and other constituent cells by tight junctions.
Type II pneumocytes also play a vital role in acting as progenitor cells to replace injured or
damaged Type I pneumocytes.

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 Figure 15B. Outline of the Gas-exchange Portion
Nasal cavity
The nose, as the primary mode of entry of air into the airway, has both respiratory and
olfactory functions. In its respiratory capacity, it modifies the air so that gaseous exchange will
occur more efficiently in the lungs, while in its olfactory capacity, it detects various odors and
transmits those impulses to the brain for interpretation.
Nasal vestibule
Entering the nares, or nostrils, the nasal vestibule is lined by keratinized stratified
squamous epithelium – a continuation of the cutaneous lining from the external nose. It is also
equipped with modified hairs, called vibrissae that filter out larger particles from inspired air. The
membrane transitions from keratinized stratified squamous epithelium to pseudostratified

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columnar ciliated epithelium with goblet cells (also called respiratory epithelium) at a point known
as the limen nasi.

Figure 15C. Respiratory Mucosa of the Nasal Cavity

Cell types
There are several cell types found in the epithelium that make olfaction possible. Air is first
directed towards the olfactory epithelium by the turbinates (bones in the conchae that support the
mucosa).
In the lamina propria, Bowman’s glands (also called olfactory glands) produce serous
secretions that dissolve odiferous particles so that they can interact with the olfactory cilia. The
olfactory cilia are short hair-like projections that extend into the mucous lining to detect and
transmit odors through the olfactory nerve cells.
Olfactory nerve cells are bipolar neurons span the thickness of the epithelium. The impulses
from the olfactory cilia are transmitted by nerve fibers from the olfactory cells that travel through
the cribriform plate of the ethmoid bone. The afferent fibers then enter the cranial cavity and
synapse with mitral cells in the olfactory bulb (CN I).
Sustentacular (supportive) cells distributed throughout the epithelium are interspersed with
olfactory nerve cells and basal cells proximal to the cribriform plate of the ethmoid bone. The cell

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shapes are hard to distinguish; so, the position and shape of the nuclei are used to distinguish the
cell types.
• The nuclei of the basal cells are spherical and proximal to the cribriform plate of the
ethmoid bone.
• The nuclei of sustentacular cells are more elongated and distal to the cribriform plate of the
ethmoid bone.
• The nuclei of the olfactory nerve cells are seen between those of the basal and sustentacular
cells.
• The mucosa of the paranasal sinuses is also respiratory epithelium. The only difference is
that the epithelium is thinner and has fewer goblet cells and serous and mucous glands. The
paranasal sinuses are typically devoid of lymphoid tissue.
Pharynx and epiglottis
Pharynx
The epithelia of the pharyngeal portion of the conducting zone changes with respect to each
pharyngeal segment. In the nasopharynx, the epithelium is continuous with that of the nasal cavity.
The ciliae here continues to wharf foreign particles through the pharynx to be swallowed.
In the oropharynx and laryngopharynx, the epithelium transitions to non-keratinized
stratified squamous epithelium. This durable epithelium is better suited to accommodate friction
associated with swallowing food. Additionally, lymphatic aggregates (distributed throughout the
mucosa) act as a first contact point for the immune system to sort through particles entering the
body (see Waldeyer’s Ring).

Figure 15D. Section of the Pharynx

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Epiglottis
The epiglottis is a cartilaginous structure located cranial to the larynx. It projects
posterosuperior to separate the pharynx from the larynx and prevents food from entering the lower
airway during swallowing.
The mucosa of the lingual surface of the epiglottis (as well as half of the laryngeal surface)
is continuous with that of the laryngopharynx. It is lined with stratified squamous non keratinized
epithelium (lingual mucosa); the other half of its laryngeal surface is lined by pseudostratified
ciliated columnar epithelium. Deep within the lamina propria of the mucosa are seromucous
glands.
Elastic cartilage in the center of the epiglottis provides scaffolding for the overlying
mucosa. Both surfaces of the epiglottis are equipped with diffuse lymphoid tissue and taste buds.

Figure 15E. Section of the Epiglottis

Larynx
Pseudostratified columnar ciliated epithelium with seromucous glands in its lamina propria
(laryngeal mucosa) continues in to the larynx and covers the false vocal fold and the end of the
laryngeal ventricle (a depression between the false vocal fold and the true vocal cord).
Goblet cells, seromucous glands, lymphatic nodules and adipocytes are observed
throughout the lamina propria to the end of the ventricle. The cilia assists in retaining the mucous

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lining, which helps to reduce damage caused during phonation. The large concentration of
lymphatic nodules in the ventricle has led to it being referred to as the laryngeal tonsils.
Passing the lower border of the ventricle, the epithelium changes again to non-keratinized
stratified squamous epithelium that covers the true vocal cords. At this point, the lamina propria is
avascular, thin, and lacks glands and lymphatic tissue. The additional cell layers replace those lost
during the closed phase of vibration.
Dense elastic fibers of the vocalis ligament project into the lamina propria and attaches to
the vocalis muscle (skeletal muscle). The epithelium again changes to pseudostratified ciliated
columnar epithelium with the cricoid cartilage (hyaline) forming the lower border between the
larynx and the trachea.

Figure 15F. Section of the Larynx

Trachea
The trachea is attached to the cricoid cartilage of the larynx by the cricothyroid membrane
and lies anterior and adjacent to the esophagus. It is a mucocartilagenous tube that is completed
posteriorly by smooth trachealis muscle. The hyaline cartilage rings prevent the airways from
collapsing during inspiration.
Along the convexity of the C-shaped rings, the adventitia contains numerous adipocytes,
blood vessels and nerves, and blends with the perichondrium of the hyaline cartilage.

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 In the concavity of the cartilaginous rings, the submucosa has numerous seromucous
glands, blood vessels, loose connective tissue fibers and scattered lymphatic tissue. The lumen of
the trachea has numerous mucosal folds along the posterior wall, where there is no hyaline
cartilage.
Throughout its length, the lumen is lined by pseudostratified ciliated columnar epithelium
with goblet cells (respiratory epithelium).

Figure 15G. Cross-section of the Trachea

Bronchial tree
Primary bronchi
After about 10 – 15 cm, the trachea bifurcates at the carina to form a left and a right primary
bronchus. The bronchi are also kept patent by C-shaped rings of hyaline cartilage and their lumens
are also lined with respiratory epithelium.
Secondary bronchi
The primary bronchi enter the lungs and further divide into secondary (intrapulmonary)
bronchi. These smaller bronchi are kept open by plates of hyaline cartilage, instead of the C-shaped
rings observed in the trachea and primary bronchi. The lining of respiratory epithelium continues
from the primary bronchi into the lumen of the secondary intrapulmonary bronchi.
The lamina propria is circumscribed by a thin layer of smooth muscle that also separates
the former from the submucosal layer (containing seromucous glands). The presence of the
muscular layer causes significant mucosal folding along the lumen of the intrapulmonary bronchi.

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Tertiary bronchi
Each secondary bronchus then divides into a tertiary bronchus, with a smaller lumen. The
hyaline plates are still present but are smaller and further apart than those around the secondary
bronchi. The mucosa of the lumen also demonstrates folding due to the smooth muscles in the wall
of the bronchus.
Seromucous glands and smaller arteries and veins can also be observed in the submucosa
and surrounding connective tissue, respectively. At this level, alveoli are now visible around the
bronchi, but they do not communicate with them.

Figure 15H. Cross-section of Bronchus

Terminal bronchioles
The tertiary bronchi continue to divide into smaller tubular structures called terminal
bronchioles. The epithelial lining of the lumen of the bronchioles differs from that of the bronchi.
Simple columnar ciliated cells now line the numerous mucosal folds.
The sub-epithelial glands and hyaline cartilaginous plates are absent in this region of the
airway. Structural support is instead provided by fibrous connective tissue along with more
prominent smooth muscle layers.
Also present in the terminal bronchioles are exocrine bronchiolar cells or club cells
(formerly known as Clara cells). These non-ciliated cuboidal cells contribute to the production of
surfactant (reduces tension in the narrow lumen of the respiratory portion of the airway), detoxifies
air and may differentiate into bronchial epithelial cells to replace older cells.

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 Figure 15I. Terminal and Respiratory Bronchioles with Clara cells
Respiratory bronchioles
Terminal bronchioles then branch to form respiratory bronchioles. This marks the transition
point from the conducting to the respiratory portion of the respiratory system. The epithelium here
is simple cuboidal that may be ciliated proximally, but devoid of cilia distally. The smooth muscle
layer is thinner here than in the conducting portion.
Alveoli
A marked feature of the respiratory portion of the airway is gaseous exchange. The thin-
walled respiratory bronchioles branch into alveolar ducts with alveolar sacs at the end; whose
simple squamous alveolar cells (type I pneumocytes) provides an ideal environment for gases to
pass to and from adjacent capillary beds.
Type II pneumocytes are larger granular cuboidal cells that are found along points of
alveolar intersection. They (along with clara cells) are responsible for the production of surfactant.
Type II pneumocytes also act as progenitor cells for both types of pneumocytes. There are also
dust cells (alveolar macrophages) of monocytic origin that carry out a phagocytic role.

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 Figure 15J. Alveoli (Type I and Type II Pneumocytes)
Avian
The nostrils of the bird, which lead into the nasal cavity, may have a flap of horn to protect
them, known as the Operculum. The Oral Cavity and the Nasal Cavity of the bird are
interconnecting via a slit in the hard palate called the choana. Birds lack a soft palate.
There are rostral, middle, and caudal conchae arising from the lateral wall, filling part of
the nasal cavity. The rostral conchae in the vestibular region are lined with stratified squamous
epithelium. The middle conchae in the respiratory region are lined with respiratory epithelium.
The caudal conchae in the olfactory region are lined with olfactory epithelium. The infraorbital
sinus is a triangular cavity under the skin, rostroventral to the eye. Some marine birds have a salt
gland (nasal gland) which excretes sodium.
The larynx is on the floor of the oropharynx supported by cricoid and paired arytenoid
cartilages which are different in structure to those in mammals. There is no epiglottis and there are
no vocal folds - birds vocalize using a syrinx. Lining epithelium is pseudostratified columnar
epithelium with goblet cells.
The avian trachea is composed of tightly stacked cartilages which are shaped similarly to
signet rings. They are complete with no dorsal space as in the mammalian trachea and overlap
considerably. The trachea can be palpated on the right side of the neck; it runs alongside the
esophagus. The trachea is lined with respiratory epithelium (pseudostratified columnar with goblet
cells). The trachea bifurcates into two main bronchi as in mammals. The syrinx is formed by this
terminal part of the trachea. The lining epithelium of syrinx is simple cuboidal with goblet cells.

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 Avian lungs are relatively compact, with a bird's lungs being approximately 50% as large
as the lung of a mammal of a similar size. The lungs are unlobed and do not have the capacity to
expand due to the close arrangement between the finite gas exchange structures, i.e. the air
capillaries and blood capillaries and scanty connective tissue. The lungs are positioned in the
craniodorsal region of the body and are deeply indented by both the thoracic vertebrae and ribs.
Birds do not have a pleural cavity as the lungs do not expand, thus the membranes are not
necessary. One primary bronchus from the trachea enters each lung, narrowing as it travels
through, and communicates with the abdominal air sac. This bronchus gives off branches as it
travels through the lung, known as secondary bronchi. Each of these gives off a further 400-500
parabronchi. The parabronchi give rise to atria. The atria form infundibulae from which the air
capillaries emerge. It is in the walls of the latter structures that gaseous exchange takes place.

Figure 15K. Cross-section of Avian Lung

Birds lack a diaphragm, and their thoracic and abdominal cavities are continuous. The bird
has a number of thin walled, easily distensible air sacs which can extend to approximately 10x the
volume of the lungs. Theye are present within body cavities, and extend into some specific bones
to take the place of the bone marrow. This has the added function of reducing the weight of the
bone, as they are essentially filled with air. The air sacs create unidirectional flow of air to
maximize oxygen extraction and reduce heat production during flight. Air sacs are lined by simple
squamous or simple cuboidal epithelium.
The birds have 9 air sacs:
• Cervical (x2) - extend within the cervical and thoracic vertebrae.
• Clavicular - lies within the thoracic inlet, surrounding the heart, and within the humerus in
the forelimb.
• Cranial Thoracic (x2) - these are ventral to the lungs.
• Caudal Thoracic (x2) - located between the body wall and the thoracic air sacs.
• Abdominal (x2) - these are the largest air sacs and fill the caudodorsal region of the
abdomen, in contact with small and large intestines, kidneys and reproductive organs. In
addition, these air sacs utilize space within the acetabulum and synsacrum.

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 The cervical, clavicular, and cranial thoracic air sacs form one functional group - cranial
and the caudal thoracic and abdominal air sacs forming another, caudal functional group. The air
sacs have a vital role in ventilation, but do not have the capacity for gaseous exchange.

Figure 15L. Outline of Avian Air Sacs

Avian Gas exchange takes place not in alveoli, as in mammals, but within air capillaries
which are extensions of the parabronchial lumen. They are an interconnecting network of loops,
and closely intertwine with blood capillaries. The air capillaries and blood capillaries are arranged
so that flow is crosscurrent. This makes the gaseous exchange, which occurs from one to the other,
extremely efficient.

Figure 15M. Air Capillaries of Avian

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Learning Activity. Discuss the main differences between the respiratory system of mammals
and avian species.

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