Anatomy III: Blood and the Cardiovascular and Respiratory Systems

Embryology of the Respiratory System

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Anatomy III: Blood and the
Cardiovascular and Respiratory
Systems
Dr. José Luis Monroy Antón
6 CMLesson 8
Embryology of the respiratory
system

Formation of the Lung Buds

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2Formation of the lung buds
• At 4th week, the mesoderm increases the
production of Retinoic Acid
. This acid increases the production of TBX4,
that stimulates the ventral wall of the foregut,
where appears an outgrowth called lung bud
• So remember: the epithelium of the internal
lining of the larynx, trachea, bronchi and
lungs has an endodermal origin
• However, the cartilaginous, muscular, and
connective tissue components of the trachea
and lungs are derived from splanchnic
mesoderm surrounding the foregut
Respiratory
diverticulum
Stomach
Heart
Liver bud
Duodenum
Vitelline
duct
Midgut
Allantois
Hindgut
Cloacal
membrane
als-R

Lung Bud Development

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3Lung buds
• At the beginning, the lung bud is
communicated with the foregut,
as shown in the picture
• Then, the bud is going to grow
and expand caudally
• As it expands, two longitudinal
ridges will separate it from the
foregut. These are the
tracheosophageal ridges
• These ridges will fuse to form the
tracheoesophageal septum
Openings of
pharyngeal pouches
Attachment of
buccopharyngeal
membrane
Respiratory
diverticulum
Laryngotracheal
orifice

Tracheoesophageal Septum Formation

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4Check the formation of the tracheoesophageal septum,
splitting the foregut into esophagus and trachea with lung buds
Tracheoesophageal
ridge
Foregut
Esophagus
Trachea
Respiratory
diverticulum
1
Lung
buds

Division of the Foregut

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5Division of the foregut
• The foregut is divided into:
- Esophagus: the dorsal portion
- Trachea and lung buds: the
ventral portion
. Both parts are still communicated
through the laryngeal orifice
Tuberculum impar
Lateral lingual swelling
I
Foramen
cecum
IV
Epiglottal
swelling
Laryngeal
swellings
VI
Laryngeal
orifice

Abnormalities in Esophagus/Trachea Partitioning

Tracheoesophageal Fistulas (TEF)

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6Abnormalities in esophagus/trachea partitioning
• Failures in the formation of the septum (1/3000
births) may result in:
- Esophageal atresia
- Tracheoesophageal fistulas or TEF
• Almost 90% of the cases it consists on an
esophageal terminal pouch + a fistula from the
trachea to the rest of the esophagus, as shown
at the picture
• They may be combined with other birth defects:
- Cardiac abnormalities in 1/3 of the cases
- Association VACTERL, that include
vertebral abnormalities, anal atresia, TEF,
limb defects and other abnormalities
Proximal blind-
end part of
esophagus
Trachea
Bifurcation
Tracheoesophageal
fistula
Bronchi
Distal part of
esophagus

Complications of TEFs

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7Abnormalities in esophagus/trachea partitioning
• At the pictures, other variants of abnormalities with
very low rate, less than 4% of the cases
• Main complications of the TEFs:
- Polyhydramnios: because the swallowed
amniotic fluid does not pass to the
stomach/intestines
- Pneumonia: due to the pass of gastric content to
the trachea

Formation of the Larynx

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8Formation of the larynx
• Endoderm: will form the internal lining of the
larynx
• Mesenchyme: the mesenchyme of the 4th and
6th pharyngeal arches will form the laryngeal
cartilages and muscles
- This mesenchyme proliferates, so the
laryngeal orifice will change its shape from I
to T
. We will be able to recognize the adult shape of
the larynx when the two arches are transformed
into these laryngeal cartilages:
- Thyroid
- Cricoid
- Aritenoids
6 weeks
Lingual swelling
1
II
Foramen
cecum
Epiglottal
swelling
IV
VI
Arytenoid swellings
12 weeks
Body of tongue
Epiglottis
-
Arytenoid swellings
Laryngeal
orifice

Formation of the Laryngeal Ventricles

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9Formation of the laryngeal ventricles
• While the cartilages are formed, the epithelium also quickly
proliferates closing temporally the lumen
• The subsequent vacuolization and recanalization produces two
lateral recesses: laryngeal ventricles
• They are surrounded by four folds that will develop into:
- Two vestibular folds, the false vocal cords
- Two vocal folds, the true vocal cords

Vagus Nerve Innervation of the Larynx

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10Vagus nerve: innervation of the larynx
So, if the laryngeal muscles are
derived from the mesenchyme
of 4th and 6th pharyngeal
arches, all the laryngeal
muscles will be innervated by
the X Vagus nerve:
• Superior laryngeal nerve:
for the derivatives of the 4th
pharyngeal arch
• Recurrent laryngeal
nerve: for the derivatives 6th
pharyngeal arch
Trigeminal ganglion
Facial nerve
V
X
VII
IX
Ophthalmic branch
nerve V
Vagus
nerve
Maxillary branch
nerve V
Mandibular branch
nerve V
Glossopharyngeal
nerve
Copyright @ 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins

Pseudoglandular Period: Bronchi Formation

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11Pseudoglandular period: Formation of the bronchi
• At 5th week, each of the two lung buds enlarge
to form the two main bronchi
- Right main bronchus forms three
secondary bronchi
- Left main bronchus forms two secondary
bronchi
• They anticipate the number of lobes that each
lung will have
• The lung buds continue their expansion
growing in caudal and lateral directions, into
two spaces called the pericardioperitoneal
canals
Trachea
Lung
buds
Left bronchus
Left upper
lobe
Right upper lobe
Right
middle lobe
Right lower lobe
Left
lower
lobe

Dividing Pericardial and Peritoneal Cavities

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12Dividing the pericardial and peritoneal cavities
Pericardio-peritoneal canals
. The canals lie on both sides of the foregut and are
gradually filled by the lung buds as they grow
• The separation of the peritoneal and pericardial
cavities are due to two folds:
- Pleuro-peritoneal fold separates the pericardio-
peritoneal canal from the peritoneal cavity
- Pleuro-pericardial fold separates the pericardio-
peritoneal canal from the pericardial cavity
• The remaining spaces form the primitive pleural
cavities
Pharynx
Trachea
Parietal
pleura
Lung bud
Pericardioperitoneal
canal
Visceral
pleura
Visceral peritoneum

Formation of the Pleura

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13Formation of the pleura
• Visceral pleura: comes from the mesoderm
that covers the outside of the lung
• Parietal pleura: comes from the somatic
mesoderm layer that covers the inner body
wall
• Pleural cavity: the space between both
pleurae
Trachea
Pleural cavity
Bronchus Visceral
pleura
Parietal pleura

Formation of Tertiary Bronchi

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14Formation of the tertiary bronchi
• Branching is regulated by epithelial-mesenchymal interactions between:
- Endoderm: of the lung buds
- Mesoderm: splanchnic mesoderm that surrounds the buds
• Secondary bronchi continue dividing forming 10 tertiary/segmental bronchi
• At the 6th month, we can find about 17 generations of subdivisions
• Early after the birth, bronchi can even produce 6 additional divisions
. Meanwhile, the lungs are assuming a more caudal position: at birth the
carina is located at T4 level

Maturation of the Lungs

Canalicular Phase

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15Maturation of the lungs
Canalicular phase:
• Phase from 4th to 7th month, in which the bronchioles divide
into smaller canals
. In this phase the vascular supply also increases
• Terminal bronchioles divide to form respiratory bronchioles
• Each respiratory bronchiole divides into 3-6 alveolar ducts
. The ducts end in terminal sacs or primitive alveoli,
surrounded by flat alveolar cells very near to the surrounding
capillaries
Blood
capillaries
Respiratory
bronchiole
O
Lung
epithelium
o
O
Terminal
bronchiole

Canalicular Phase Progression

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16Canalicular phase:
• The first picture (14th week) represents the beginning of the canalicular phase, check the cuboidal cells
lining the respiratory bronchioli
• At the second picture (7th month) the cuboidal cells become very thin and close to the endothelium of
blood capillaries, and form terminal sacs
Blood
capillaries
Respiratory
bronchiole
O
Lung
epithelium
0
0
S
O
O
S
0
Terminal
bronchiole
Thin
squamous
epithelium
Flat endothelium
cell of blood
capillary
Terminal
sacs
O
J
O
0
00
Respiratory
bronchiole

Terminal Sac Period

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17Terminal sac period
• At the end of 7th month we have
enough alveolar sacs to allow the
adequate gas exchange
• This feature normally marks the
survival limit of a premature fetus
• At the picture (newborn) we can see:
- Thin squamous epithelial cells or
alveolar epithelial cells type 1
- Surrounding capillaries protruding
into mature alveoli.
Thin squamous
epithelium
Blood
capillary
0
00
Alveolar
duct
0
0
'Lymph
capillary
Mature alveolus
Respiratory bronchiole

Tracheobronchial Tree Defects

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18Tracheobronchial tree defects
• Rare gross abnormalities: absence of lungs,
agenesia of one lung, blind-end trachea ...
• More common are the abnormal divisions of the
bronchial tree, like supernumerary lobules, without
functional significance
• Ectopic lung lobes from the trachea: formed by
additional respiratory buds
• Congenital cysts of the lung, small and multiple like a
honeycomb, formed by dilation of terminal or larger
bronchi. They may cause chronic infections due to their
poor drainage
Lef
Right
Apical
lobe
Cardiac
lobe
Accessory
lobe
Diaphragmatic
lobe
R

Alveolar Epithelial Cells Type II

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19Alveolar epithelial cells type II
• Third kind of cell, developed from the 6th month
• They produce surfactant, that decreases the
surface tension of the air-alveolar interface
• The amount of surfactant increases significantly
during the last 2 weeks before birth
• The liquid that fills the lungs consists in:
- Liquid with a high chloride concentration
– Little protein
- Mucus from the bronchial glands
- Surfactant from the type II cells

Surfactant at Birth

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20Surfactant at birth
• At birth, most of the lung fluid is reabsorbed by the
capillaries
. However, the surfactant remains deposited as a
thin phospholipid coat on alveolar cell
membranes
. At the first breath, the air enters at the alveoli but
the surfactant coat prevents an air-blood interface
with high surface tension
• Without the surfactant, the alveoli would collapse
during expiration
Normal alveoli
Collapsed alveoli

Surfactant Defects

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21Surfactant defects
• When surfactant is insufficient, the air-blood membrane
tension becomes high, and at the expiration the alveoli
collapse, causing hyaline membrane disease, also called
respiratory distress syndrome or RDS
• The RDS causes high mortality in premature infants because
the alveoli contains a fluid with many hyaline membranes and
protein content
• We can treat the disease:
- Giving artificial surfactant to the premature babies
- Giving glucocorticoids to the mother, that stimulate the
surfactant production

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22