Histology of the Respiratory system
By
Safaa El Bialy (MD, PhD)
Objectives
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Describe the histology of the respiratory epithelium, and demonstrate the ability
to identify the different tissue layers making up the respiratory tract (i.e., mucosa,
submucosa, cartilage layer and adventitia).
Recognize the concept of the mucociliary blanket.
Describe the structure of the alveoli
Explain how the alveoli allow for gas exchange.
Identify the components of the trachea, bronchi and bronchioles.
Compare and contrast the conducting portion and the respiratory portion of the
respiratory system.
Respiratory system
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Anatomically Consists of :
Upper respiratory system
Nasal cavities
Sinuses
Nasopharynx
Lower respiratory system
Larynx
Trachea
Bronchi
Bronchioles and
alveoli
Respiratory system
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Conducting portion:
Nasal cavities
Nasopharynx
Larynx
Trachea, bronchi
Bronchioles and terminal
bronchioles
Function:
Provide a conduit through which
air moves to and from the lungs
Condition the inspired air
Respiratory portion
1. Respiratory bronchioles
2. Alveolar ducts
3. Alveoli
Function : gas exchange
Respiratory Epithelium
1. Most of the conducting system
is lined with ciliated C
pseudostratified columnar
epithelium
2. Goblet cells G are also
abundant in some areas (mucin
secretion)
3. Brush cells B less abundant
considered to be chemosensory
receptors
4. Basal cells, small rounded cells
on the BM, stem cells that give
rise to other type of cells
Respiratory Epithelium (brush cells)
Respiratory Epithelium (basal cells)
Trachea
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14-16 cm long tube
Extends from larynx (6th
cervical vertebra) to carina
(bifurcation) in front of
sternal angle
Lined with typical respiratory
mucosa
Numerous seromucous
glands produce watery
mucus
In the submucosa, 16-20 C
shaped rings of hyaline
cartilage keep the trachea
open
The opened part is dorsal
and bridged by trachealis
muscle (smooth) and a sheet
of fibroelastic tissue
Trachea
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Entire organ is
surrounded by an
adventitia
Cartilage
Submucosa
Adventitia
Trachealis muscle
Trachea
1. Mucosa: Typical
respiratory epithelium
(E)
2. Submucosa:
• Connective tissue (CT)
• and seromucous glands
(G).
3. Cartilage
• C shaped rings Hayline
cartilage (C)
• perichondrium (P)
4. Adventitia
Cartilage
Submucosal mixed glands
Cartilage
Perichondrium
Chondrocytes
Extracellular matrix
Bronchial Tree
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The trachea → 2 primary bronchi
→ 3 secondary lobar bronchi in the
right lung and 2 in the left lung
(same histology of the trachea)
These Lobar bronchi → tertiary
(segmental) bronchi → conducting
bronchioles→ terminal bronchioles
→ respiratory bronchioles
Bronchi
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Most cartilage rings
completely encircles the
lumen in 1ry bronchi
The rings are gradually
replaced with isolated plates
of hyaline cartilage
Abundant mucus and serous
glands
Smooth muscles in the
lamina propria become more
abundant in the smaller
bronchioles
Tertiary bronchus
Histology of Bronchi versus Trachea
• Mucosa of larger bronchi
structurally similar to mucosa
of trachea except for the
cartilage & smooth muscle
• Cartilage rings completely
encircle the lumen of primary
bronchi but as bronchial
diameter decreases cartilage
rings replaced by isolated
pieces of hyaline cartilage
• Bronchial lamina propria has
spirally arranged smooth
muscle which becomes more
prominent in smaller
bronchioles.
Large bronchus
smaller bronchus
Bronchioles
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No cartilage nor glands
Ciliated pseudostratified
columnar epithelium in
larger bronchioles
Ciliated simple columnar
or cuboidal epithelium in
the smaller terminal
bronchioles (Clara cells)
Lamina propria (smooth
muscles and elastic fibers)
Musculature of bronchi
and bronchioles is under
influence of vagus nerve
(constricts) and SN system
(dilates)
A large bronchiole
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characteristically folded respiratory
epithelium
The lamina propria has become a
thin band
No glands
The muscularis, which appears as
discontinuous bundles of smooth
muscle, is relatively thick
A smaller bronchiole
• The epithelium is
simple columnar
• High elastic content
(arrowhead) associated
with the muscle.
A very small bronchiole
• The epithelium (E) is
reduced to simple low
columnar and the
several layers of smooth
muscle cells (arrows)
comprise a high
proportion of the wall.
Terminal Bronchioles
a) Last part of conducting system
before sites of gas exchange
• Ciliated cuboidal epithelium
(very few)
• 1 or 2 layers of smooth
muscles
b) Clara cells
1. Bulging domes of apical
cytoplasm with granules
2. Non ciliated
3. secrete surfactant and have
various defensive roles.
4. Produce enzymes that help
breakdown of mucus
Respiratory Bronchioles
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Transition zone between the
conducting and respiratory
zone
Mucosa is similar to terminal
bronchioles
The walls are interrupted by
the openings to saclike alveoli
Epithelium in that region is
continuous with the
squamous alveolar lining cells
More distally the number of
the alveoli increases and the
distance is reduced
Respiratory Bronchioles
• Very similar to that of a terminal
bronchiole,
• It has Clara cells lying almost
directly over smooth muscle
bundles.
• The arrow shows where these
Clara cells can be seen most
clearly.
• The alveoli which form
outpocketings from the wall are
lined by very squamous cells
called alveolar type I cells not
identifiable here.
• Other alveoli are seen at the right
of the field of view.
Regular Vs terminal Vs respiratory bronchiole
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Regular bronchiole with ciliated
pseudostratified epithelium or ciliated
columnar
Terminal bronchiole ciliated cuboidal
with non-ciliated Clara cells.
The arrow is pointing at the last of the
ciliated cells of the regular bronchiole.
Respiratory bronchiole, marking the
beginning of the respiratory portion of
the respiratory tree (cuboidal with
some Clara cells)
The dip in the respiratory bronchiole is
an alveolus, one of the air sacs in which
gas exchange occurs.
Histology of Bronchioles versus Bronchi
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Bronchioles lack cartilage & glands in mucosa
Epithelium less complex in bronchioles; change from ( PsCc ) in larger
bronchioles , with decrease in height to ciliated simple columnar /cuboidal in
terminal bronchioles
• Goblet cells disappear in terminal bronchiole
• Terminal bronchioles
1. have exocrine bronchiolar cells called Clara cells,
2. serve as a region of transition between conducting & respiratory portions of
respiratory system.
Medical Application (FYI)
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The bronchiolar muscle layer is greater than the bronchial one
Increased airway resistance in asthma is believed to be due mainly to contraction
of bronchiolar smooth muscle layer
The increase in bronchiolar diameter in response to stimulation of the epinephrine
and other sympathomimetic drugs are frequently used to relax smooth muscle
during asthma attacks
Mucociliary Escalator (Blanket)
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Covers most of the bronchi,
bronchioles & nose.
Composed of mucous producing
goblet cells & ciliated epithelium
Cilia beats continuously pushing
mucous up & out of the throat
Microorganisms are caught in
the sticky mucous (blanket) and
moved up by the mucociliary
escalator
Smoking Mucociliary Escalator (Blanket)
• Smoking leads to reduction in ciliated cells
caused by excessive intake of CO
• Results in decreased movement of the mucous
layer
• Frequently leads to congestion of the smaller
airways
The respiratory zone
1. Respiratory bronchioles
• Serve both as conducting and respiratory portions. The thin-walled alveoli
open in their lumen.
2. Alveolar ducts
• These have many of the alveoli opening into their lumen and their openings are
separated by very small segments or knobs of smooth muscles.
3. Alveolar sacs
• Each has many alveoli opening into its lumen & without any wall and muscles
between their openings.
4. Alveoli
• These are thin walled sacs, whose surfaces are sites of gas exchange
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Alveolar Ducts
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Alveolar ducts AD and sacs AS
are lined by attenuated
squamous alveolar cells
Sparse strands of smooth
muscle are present in alveolar
duct absent in alveolar sac &
alveoli (A)
Elastic & Reticular fibres, form
a network encircling openings
of alveolar sacs & alveoli
Reticular fibres ; provide
support & prevent over
distension & damage to
delicate capillaries & thin
alveolar septa
Alveoli
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Sac like evaginations
(honeycomb)
• Walls are specialized to enhance
diffusion between the external
and internal environment
• interalveolar septum is present
between alveoli
• Blood air barrier (respiratory
membrane):
1. Alveolar cells
2. Endothelial cells
3. Fused basal laminae of alveolar
cells and capillary endothelial
cells
Alveoli
Alveolar sac
Alveolus
Alveoli
Smooth muscles
Alveolar Septa
Type I alveolar cells (type I pneumocytes)
• Squamous cells lining 97% of the alveolar
surface
• Function is to provide a barrier of large
surface area and minimal thickness for
efficient gas exchange between alveolar air
and capillary blood.
Type II alveolar cells (type II pneumocytes)
• Interspersed between type I cells
• Found where the alveolar walls unite
• Contain lamellar bodies(secrete surfactant)
• Type II pneumocytes also mitotically divide
and differentiate into type I pneumocytes in
response to injury
Endothelial cells of capillaries
Interstitial cells
• Fibrobalsts
1. Produce collagen, elastin and PGs
2. Repair and remodelling
Alveolar macrophages
Interalveolar Septum
Alveolar space
Alveolar septum
Capillary
Pneumocyte I
Pneumocyte II
Alveolar Macrophages
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Dust cells
Found in alveoli and
interalveolar septum
Slightly darker in the lungs
due to their content of dust
and carbon
Filled macrophages migrate
into bronchioles for removal
in the pharynx or exit the
lungs in the lymphatic
drainage
macrophage
Medical application (FYI)
• In CHF, the lungs become congested with blood, and
erythrocytes pass in alveoli to be phagocytosed by
macrophages
• These macrophages are called heart failure cells
• Identified by a positive histochemical reaction from iron
pigment (hemosiderin)
• Increased production of collagen is common and many
diseases leading to respiratory distress are known to be
associated with lung fibrosis
Medical Application (FYI)
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Pulmonary stress syndrome
Deficiency of surfactant in the
premature babies
With surfactant alveoli need less
inspiratory force to inflate
Life threatening condition
Alveoli are collapsed and
respiratory bronchioles and
alveolar ducts are dilated with
edema fluid
Medical Application (FYI)
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Emphysema
Chronic lung disease
Destruction of the interalveolar wall
Enlargement of the air space distal to the
bronchioles
• Gradual and results in insufficiency
• Cigarette smoking is a major cause
Regeneration of the alveolar lining
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Toxic gases can kill type I and II cells lining pulmonary alveoli
Death of type I cells increases the mitotic activity in the remaining type II cells.
The progeny of Type II cells become both cell types
Summary
Cartilage
• Trachea C rings of cartilage: Primary & Secondary bronchi:
cartilage completely encircle the lumen
• Tertiary (segmental ) bronchi : isolated pieces of hyaline
cartilage
• Bronchioles: cartilage absent
Epithelium
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Trachea to Bronchioles :
Pseudostratified columnar ciliated with goblet cells.
Terminal Bronchioles:
Decrease in complexity of epithelium: simple columnar or
cuboidal + ciliated.+ clara cells
• No sero-mucinous glands & goblet cells disappear
3. Respiratory Bronchioles :
• Cuboidal , simple & non ciliated (Clara cells).
Cartilage absent
Summary Histology Respiratory System
• Smooth muscle: Trachea C shaped ring of cartilage bridged by
trachealis muscle
• Bronchi & bronchioles (terminal & respiratory) contain spiral
bands of smooth muscle
• Elastic Fibres: Abundant through all levels of respiratory
system