EMBRYOLOGY OF

RESPIRATORY SYSTEM

ONANUGA I.O. (PhD)

 Formation of the Lung Buds
 The upper R.S.E-Pharyngeal Apparatus
 The lower respiratory organs (larynx, trachea,
bronchi, and lungs) begin to form during the fourth
week of development.
 A respiratory diverticulum (lung bud) appears
as an outgrowth from the ventral wall of the foregut.

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Formation of the Lung Buds(contd.)
 The location of the bud along the gut tube is
determined by signals from the surrounding
mesenchyme, including fibroblast growth
factors (FGFs) that “instruct” the endoderm.

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Formation of the Lung Buds (contd.)

 The epithelium of the internal lining of

the larynx, trachea, and bronchi, as
well as that of the lungs, is entirely of
endodermal origin.
 The cartilaginous, muscular, and
connective tissue components of the
trachea and lungs are derived from
splanchnic mesoderm surrounding
the foregut.

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Formation of the Lung Buds (contd.)
 At the beginning, the lung bud is in open
communication with the foregut.
 When the diverticulum expands caudally, however,
two longitudinal ridges, the tracheoesophageal
ridges, separate it from the foregut.

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Formation of the Lung Buds (contd.)
 Tracheoesophageal its communication with
ridges later fuse to form the pharynx through the
tracheoesophageal laryngeal orifice
septum.
 The foregut is divided
into a dorsal portion, the
esophagus, and a
ventral portion, the
trachea and lung
buds.
 The respiratory
primordium maintains
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 Anomalies of lung bud formation
 Abnormalities in partitioning of the esophagus and
trachea by the tracheoesaphageal septum result in
esophageal atresia with or without
tracheoesaphageal fistulas (TEFs).
 Various esophageal atresia and/or tracheoesophageal
fistulae exists as shown in the next slide.
 A. The most frequent abnormality (90% of cases)
occurs with the upper esophagus ending in a blind
pouch and the lower segment forming a fistula with the
trachea.
 B. Isolated esophageal atresia (4% of cases).
 C. H-type tracheoesophageal fistula (4% of cases).
 D7 and E. Other variations (each 1% of cases). 12/16/2024
Anomalies of lung bud formation

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Anomalies of lung bud formation

 A complication of some TEFs is

polyhydramnios, since in some types of
TEF amniotic fluid does not pass to the
stomach and intestines.
 Also, gastric contents and/or amniotic
fluid may enter the trachea through a
fistula, causing pneumonitis and
pneumonia.
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 Larynx

 The internal lining of the

larynx originates from
endoderm, but the cartilages
and muscles originate from
mesenchyme of the fourth
and sixth pharyngeal
arches.
 The laryngeal cartilages
develop from mesenchyme
that is derived from neural
crest cells.
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 Larynx Contd.
 The mesenchyme at the cranial end of the
laryngotracheal tube proliferates rapidly,
producing paired arytenoid swellings

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 Larynx Contd.
 As a result of rapid proliferation of this
mesenchyme, the laryngeal orifice changes in
appearance from a sagittal slit to a T-shaped
opening
 Subsequently, the mesenchyme of the two arches
transforms into the thyroid, cricoid, and
arytenoid cartilages, the characteristic adult
shape of the laryngeal orifice is recognized.

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 Larynx Contd.
 These swellings grow toward the tongue, converting
the slit-like aperture (the primordial glottis) -into a
T-shaped laryngeal inlet and reducing the
developing laryngeal lumen to a narrow slit.
 The laryngeal epithelium proliferates rapidly,
resulting in temporary occlusion of the laryngeal
lumen.
 Recanalization of the larynx normally occurs by the
10th week.
 The laryngeal ventricles form during this
recanalization process.
 These recesses are bounded by folds of mucous
membrane
13 that differentiate into the false and true
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vocal cords.
 A. 6 weeks. B. 12 weeks.

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 Larynx (contd.)

 The epiglottis develops from the caudal

part of the hypopharyngeal eminence, a
prominence produced by proliferation of
mesenchyme in the ventral ends of the
third and fourth pharyngeal arches.
 The rostral part of this eminence forms
the posterior third or pharyngeal part of
the tongue.

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 Larynx (contd.)

 Since musculature of the larynx is derived

from mesenchyme of the fourth and sixth
pharyngeal arches, all laryngeal muscles
are innervated by laryngeal branches of
the vagus nerve.
 The superior laryngeal nerve innervates
derivatives of the fourth pharyngeal arch,
and the recurrent laryngeal nerve
innervates derivatives of the sixth
pharyngeal arch
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 Clinical application
 Laryngeal Atresia - A rare anomaly resulting from
failure of recanalization of the larynx, leading to
obstruction of the upper fetal airway- congenital
high airway obstruction syndrome (CHAOS)
CLINICAL feafures –
1. lungs are enlarged and echogenic,
2. the diaphragm is either flattened or inverted,
3. fetal ascites and/or hydrops (accumulation of serous
fluid in the intracellular spaces causing severe
edema),
4. laryngeal web
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 Development of the trachea
 Endodermal lining of
the laryngotracheal
tube distal to the
larynx differentiates
into the epithelium
and glands of the
trachea and the
pulmonary epithelium.
 Cartilage, connective
tissue, and muscles of
the trachea are
derived from the
splanchnic
mesenchyme
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surrounding the
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laryngotracheal tube.
 Development of the trachea Contd.
 Successive stages in the development of the
tracheoesophageal septum during the fourth and fifth
weeks. A to C, Lateral views of the caudal part of the
primordial pharynx showing the laryngotracheal
diverticulum and partitioning of the foregut into the
esophagus and laryngotracheal tube.

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Development of the trachea Contd.
 D to F, Transverse sections illustrating
formation of the tracheoesophageal
septum and showing how it separates the
foregut into the laryngotracheal tube and
esophagus. The arrows indicate cellular
changes resulting from growth.

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 Clinical application
 Tracheoesophageal Fistula - TEF
 Laryngotracheoesophageal Cleft -
persistent connection between these
normally separated structures. Symptoms
are similar to those of tracheoesophageal
fistula but aphonia (absence of voice) is a
distinguishing feature.
 Tracheal Diverticulum - This extremely rare
anomaly consists of a blind bronchus-like
projection from the trachea. The outgrowth
21may terminate in normal-appearing lung 12/16/2024

tissue, forming a tracheal lobe of the lung.

 Bronchi and Lungs development
 During its separation from the foregut, the lung bud
forms the trachea and 2 lateral outpocketings, the
bronchial buds.
 At the beginning of the 5th week, each of these buds
enlarges to form right and left main bronchi (primary).
 The right then forms 3 secondary bronchi, and the left,
2. Thus foreshadowing the 3 lobes on the right side and
2 on the left.

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Bronchi and Lungs development contd
 With subsequent growth
in caudal and lateral
directions, the lung buds
expand into the body
cavity.
 The spaces for the
lungs (the
pericardioperitoneal
canals) are narrow and
lie on each side of the
foregut.
 At this stage, the canals
are in communication
with the peritoneal and
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pericardial cavities.
 Bronchi and Lungs development
(contd.)
 The mesoderm, which
covers the outside of
the lung, develops into
the visceral pleura.
 The somatic mesoderm
layer, covering the body
wall from the inside,
becomes the parietal
pleura.
 The space between the
parietal and visceral
pleura is the pleural
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cavity. 12/16/2024
 Bronchi and Lungs
development (contd.)
 During further development, secondary bronchi divide
repeatedly in a dichotomous fashion, forming 10
tertiary (segmental) bronchi in the right lung and 8
in the left, creating the bronchopulmonary segments
of the adult lung.
 By the end of the 6th month, approximately 17
generations of subdivisions have formed.
 Before the bronchial tree reaches its final shape,
however, an additional 6 divisions form during
postnatal life.
 Branching is regulated by epithelial-mesenchymal
interactions between the endoderm of the lung buds
and splanchnic mesoderm that surrounds them, it
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involves members of the fibroblast growth factor (FGF)
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family.
 Maturation of the Lungs

 At the 7th prenatal month, the bronchioles divide

continuously into more and smaller canals
(canalicular phase) and the vascular supply
increases steadily.
 Respiration becomes possible when some of the
cells of the cuboidal respiratory bronchioles
change into thin, flat cells.
 These cells are intimately associated with
numerous blood and lymph capillaries, and the
surrounding spaces are now known as terminal
sacs or primitive alveoli.

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 Maturation of the Lungs (contd.)
 A. Canalicular period lasts from the 16th - 26th week.
Note the cuboidal cells lining the respiratory bronchioli.
 B. The terminal sac period begins at the end of the 6th and
beginning of the 7th prenatal month.
Cuboidal cells become very thin and intimately associated with
the endothelium of blood and lymph capillaries or form terminal
sacs (primitive alveoli).

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 Maturation of the Lungs (contd.)
 The cells lining the sacs, known as type I alveolar
epithelial cells, become thinner, so that surrounding
capillaries protrude into the alveolar sacs.
 This intimate contact between epithelial and
endothelial cells makes up the blood-air barrier.
 Mature alveoli are not present before birth.
 In addition to endothelial cells and flat alveolar
epithelial cells, another cell type develops at the end
of the 6th month.
These cells, type II alveolar epithelial cells, produce
surfactant, a phospholipid-rich fluid capable of
lowering surface tension at the air-alveolar interface.
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 Maturation of the Lungs

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 LUNG ABNORMALITY
Hyaline membrane disease (respiratory
distress syndrome, RDS)
•surfactant
Hypoplasia of typeⅡ alveolar cells → insufficient
→ surface tension↑ → alveoli collapse
→ difficult breath;
•Atrophied alveoli, lined with hyaline membrane made
up of plasma proteins;
•Usually seen in premature infants and accounts for
about 20% of deaths among newborns.

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 Lung anomalies
Ectopic lung lobes arising from the
trachea or esophagus.
Congenital cysts of the lung, which are
formed by dilation of terminal or larger
bronchi.
These cysts may be small and multiple, giving
the lung a honeycomb appearance on
radiograph, or they may be restricted to one
or more larger ones.
Cystic structures of the lung usually drain
poorly
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and frequently cause chronic infections.
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 THE END
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