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Pamela BL
 The
lower respiratory tract consists of the
larynx, trachea, bronchi and lungs.
 It begins to form during the fourth week(2627 days).
 The respiratory primordium is first indicated
by a median outgrowth(the laryngotracheal
groove)from the caudal end of the ventral
wall of the primitive pharynx, caudal to the
fourth pair of pharyngeal pouches.
A.Diagramatic sagittal section of the cranial half of an embryo about 26
days illustrating the floor of the primitive pharynx and the location of
laryngotracheal groove. B. Horizontal section at the level shown in A
 The
endoderm lining the laryngotracheal
groove gives rise to the epithelium and
glands of the larynx, trachea, bronchi, and
the pulmonary epithelium.
 The connective tissue, cartilage and smooth
muscle in these structures develop from the
splanchnic mesenchyme surrounding the
foregut.
 By
the end of the fourth week, the
laryngotracheal groove has evaginated to
form a pouch like laryngotracheal
diverticulum, which is located ventral to the
caudal part of the foregut.
 As this diverticulum elongates, it is invested
with splanchnic mesenchyme, and its distal
end enlarges to form a globular lung bud.
Lateral view of the caudal part of the primitive pharynx illustrating
partitioning of the foregut into esophagus and laryngotracheal tube4th-5th week
Lateral view of the caudal part of the primitive pharynx illustrating
partitioning of the foregut into esophagus and laryngotracheal tube4th-5th week
 The
laryngotracheal diverticulum soon
becomes separated from the primitive
pharynx.
 Longitudinal tracheoesophageal folds(ridges)
develop, approach each other and fuse to
form a partition known as the
tracheoesophageal septum.
Transverse sections illustrating formation of the tracheoesophageal
septum and separation of the foregut into the laryngotracheal tube
and esophagus
 This
septum divides the cranial part of the
foregut into a ventral portion, the
laryngotracheal tube(primordium of the
larynx, trachea, bronchi and lungs), and a
dorsal portion(primordium of the oropharynx
and esophagus).
 The opening of the laryngotracheal tube into
the pharynx becomes the laryngeal
aditus(orifice) or inlet of the larynx.
Lateral view of the caudal part of the primitive pharynx illustrating
partitioning of the foregut into esophagus and laryngotracheal tube4th-5th week
 The
epithelium of the internal lining of the
larynx develops from the endoderm of the
cranial end of the laryngotracheal tube.
 The cartilages of the larynx are derived from
the cartilages in the 4th and 6th pairs of the
branchial or pharyngeal arches.
 The
mesenchyme at the cranial end of the
laryngotracheal tube proliferates rapidly
producing paired arytenoid swellings.
 These swellings grow towards the tongue,
converting the slit like aperture called the
primitive glossitis into a T shaped laryngeal
aditus(inlet) and reducing the developing
laryngeal lumen to a narrow slit.
Drawings illustrating stages in development of the larynx. A.4 weeks,
B.5 weeks. The epithelium of the internal lining of the larynx is of
endodermal origin. Cartilages and muscles of the larynx arise from
mesenchyme in the 4th and 6th pairs of branchial/pharyngeal arches.
 The
laryngeal epithelium proliferates rapidly,
resulting in a temporary occlusion of the
laryngeal lumen during the 8th week.
 Recanalization of the larynx usually occurs by
the 10th week.
 The laryngeal ventricles form during this
process.
 These lateral recesses are bounded by folds
of mucous membrane that become the vocal
folds(cords) and vestibular folds.
 The
epiglottis develops from the caudal part
of the hypobranchial eminence, a
prominence produced by proliferation of
mesenchyme in the ventral ends of the 3rd
and 4th branchial/pharyngeal arches.
 The rostral part of this eminence forms the
pharyngeal part of the tongue.
C. 6 weeks, D.10 weeks. Note that the laryngeal inlet or aditus changes
in shape from slit like opening to a T shaped inlet as the mesenchyme
proliferates.
 Because
the laryngeal muscles develop from
myoblasts in the 4th and 6th pairs of
branchial/pharyngeal arches they are
innervated by the laryngeal branches of the
vagus nerves that supply these arches.
 Laryngeal
web-uncommon anomaly that
results from incomplete recanalization of the
larynx during the 10th week.
 A membranous web forms at the level of the
vocal folds(cords) partially obstructing the
airway.
 The
endodermal lining of the laryngotracheal
tube distal to the larynx differentiates into
the epithelium and glands of the trachea and
to the pulmonary epithelium.
 The cartilage, connective tissue and muscles
are derived from splanchnic mesenchyme
surrounding the laryngotracheal tube.
Drawings of transverse sections through the laryngotracheal tube
illustrating progressive stages in the development of the trachea. A,4
weeks B,10 weeks C,11 weeks.
 Tracheosophageal
fistula, an abnormal
communication or fistula between the
trachea and esophagus occurs about once in
every 2500 births, most affected infants are
males.
 In more than 85% of cases, a fistula is
associated with esophageal atresia(Herbst,
1992).
 Tracheoesophageal
fistula is the most
common anomaly of the lower respiratory
tract.
 It results from incomplete division of the
cranial part of the foregut into respiratory
and digestive portions during the 4th week.
 Incomplete fusion of the tracheoesophageal
folds produces a defective
tracheoesophageal septum and abnormal
communication between the trachea and
esophagus.
 Four
varieties of tracheoesophageal fistula
may develop.
 The most common abnormality is for the
superior portion of the esophagus to end
blindly(esophageal atresia) and for the
inferior portion to join the trachea near its
bifurcation.
 Infants
with the common type of esophageal
atresia and tracheoesophageal fistula cough
and choke on swallowing due to
accumulation of excessive amount of saliva
in the mouth and upper respiratory tract.
 When the infant swallows, it rapidly fills the
esophageal pouch and is regurgitated.
 Gastric
contents may also reflux from the
stomach through the fistula into the trachea
and lungs.
 This causes choking and may result in
pneumonia or pneumonitis(inflammation of
the lungs).
 An
excess of amniotic
fluid(polyhydramnions)is often associated
with esophageal atresia and
tracheoesophageal fistula.
 This condition develops because amniotic
fluid cannot pass to the stomach and
intestines for absorption and subsequent
transfer via the placenta to the mother’s
blood for disposal.
 Tracheal
stenosis and atresianarrowing(stenosis) and obstruction(atresia)
of the trachea are uncommon anomalies that
are usually associated with one of the
varieties of the tracheoesophageal fistula.
 Stenoses and atresias probably result from
unequal partitioning of the foregut into the
esophagus and the trachea.
 Sometimes there is a web of tissue
obstructing airflow(incomplete tracheal
atresia).
 The
bulb shaped lung that develops at the
caudal end of the laryngotracheal tube
during the 4th week divides into 2 knob like
buds.
 These endodermal buds grow laterally into
the pericardioperitoneal canals, the
primordia of the pleural cavities.
 Together with the surrounding splanchnic
mesenchyme, the bronchial buds
differentiate into the bronchi and their
ramifications in the lungs.
Development of the lungs at four weeks
Growth of developing lungs into the adjacent splanchnic
mesenchyme of the medial walls of the pericardioperitoneal canals,
five weeks.
 Early
in the 5th week each bronchial bud
enlarges to form the primordium of a
main/primary bronchus.
 The embryonic right bronchus is slightly
larger than the left one and is oriented more
vertically, this embryonic relationship
persists after birth.
 Consequently, a foreign body is more liable
to enter the right main bronchus than the
left one(Moore,1992).
Development of the bronchi at five weeks
 The
main/primary bronchi subdivide into
secondary bronchi.
 On the right, the superior secondary
bronchus will supply the superior lobe of the
lung whereas the inferior secondary bronchus
subdivides into two bronchi, one to the
middle lobe of the right lung and the other
to the inferior lobe.
 On the left, the two secondary bronchi
supply the superior and inferior lobes of the
lung.
Development of the bronchi, six weeks
 Each
secondary bronchus subsequently
undergoes progressive branching.
 Tertiary or segmental bronchi, ten in the
right lung and eight/nine in left lung, begin
to form by the 7th week.
 As this occurs, the surrounding mesenchymal
tissue also divides.
Development of segmental/tertiary bronchi at eight weeks
 Each
segmental bronchus with its surrounding
mass of mesenchyme, is the primordium of a
bronchopulmonary segment.
 By 24 weeks, about 17 orders of branches
have developed.
 An additional seven orders of airways
develop after birth.
 As
the bronchi develop, cartilaginous plates
develop from the surrounding splanchnic
mesenchyme.
 The bronchial smooth musculature and
connective tissue, pulmonary connective
tissue and capillaries are also derived from
this mesenchyme.
 As the lungs develop they acquire a layer of
visceral pleura from the splanchnic
mesenchyme.
Development of the layers of the pleura, six weeks.
 With
expansion, the lungs and the pleural
cavities grow caudally into the mesenchyme
of the body wall and soon lie close to the
heart.
 The thoracic body wall becomes lined by a
layer of parietal pleura derived from somatic
mesoderm.
 Lung
development can be divided into four
stages:
1. Pseudoglandular period
2. Canalicular period
3. Terminal sac period
4. Alveolar period
 The
pseudoglandular period(5-17 weeks); the
developing lung somewhat resembles an
exocrine gland during this period.
 By 17 wweeks all major elements of the lung
have formed except those involved with gas
exchange.
 Respiration is not possible, hence fetuses
born during this period cannot survive.
 The
canalicular period(16-25 weeks); this
period overlaps the pseudoglandular period
because cranial segments of the lungs
mature faster than caudal ones.
 During the canalicular period, the Lumina of
the bronchi and terminal bronchioles become
larger and the lung tissue becomes highly
vascular.
 By
24 weeks, each terminal bronchiole has
divided to form two or more respiratory
bronchiole.
 Each of these then divides into 3-6 tubular
passages called alveolar ducts.
Diagrammatic sketch of histological section illustrating late
canalicular period , about 24 weeks.
 Respiration
is possible toward the end of
canalicular period because some thin walled
terminal sacs(primitive alveoli) have
developed at the ends of the respiratory
bronchioles, and these regions are well
vascular zed.
 Although a fetus born toward the end of this
period may survive if given intensive care, it
often dies because its respiratory and other
systems are still relatively immature.
 The
terminal sac period(24 weeks –birth);
during this period many more terminal sacs
develop and their epithelium becomes very
thin.
 Capillaries begin to bulge into these
primitive alveoli.
 By 24 weeks, the terminal sacs are lined
mainly by squamous epithelial cells of
endodermal origin known as type I alveolar
cells/pneumocytes.
 The
capillary network proliferates rapidly in
the mesenchyme around the developing
alveoli, and there is concurrent active
development of lymphatic capillaries.
 Scattered among the squamous epithelial
cells are rounded, secretory, epithelial cells
called type II alveolar cells/pneumocytes.
Diagrammatic sketch of histological section illustrating terminal sac
period about 26 weeks
 These
cells secrete pulmonary surfactant, a
complex mixture of phospholipids which
forms as a monomolecular film over the
internal walls of the terminal sacs.
 It is recognized that the maturation of
alveolar type II cells and surfactant
production varies widely in fetuses of
different gestational ages(Chernick and
Kryger,1990).
 The
production of surfactant increases during
the terminal stages of pregnancy, particularly
during the last two weeks before a full term
birth.
 Surfactant counteracts surface tension forces
and facilitates expansion of the terminal
sacs(primitive alveoli).
 Consequently, fetuses born prematurely at
24-26 weeks may survive if given intensive
care but they suffer respiratory distress due
to surfactant defiency.
 Surfactant
production begins by 20 weeks but
it is present in very small amounts in
premature infants, it does not reach
adequate levels until the late fetal
period(Ballard, 1989).
 By
26-28 weeks after fertilization, the fetus
usually weighs about 1000gms and sufficient
terminal sacs and surfactant are present to
permit survival of a prematurely born infant.
 Before this, the lungs are usually incapable
of providing adequate gas exchange, partly
because the alveolar surface area is
insufficient and the vascularity
underdeveloped.
 It
is not the presence of thin terminal sacs or
primitive alveolar epithelium so much as the
development of an adequate pulmonary
vasculature and sufficient surfactant that are
critical to the survival of premature infants.
 The
alveolar period(late fetal period –
childhood); the epithelial lining of the
terminal sacs attentuates to an extremely
thin squamous epithelial layer.
 The type I alveolar cells become so thin that
the adjacent capillaries bulge into the
terminal sacs.
Diagrammatic sketch of histological section illustrating alveolar
period in new born infant.
 By
the late fetal period, the lungs are
capable of respiration because the
alveolocapillary membrane(respiratory
membrane) is sufficiently thin to allow gas
exchange.
 Although the lungs do not begin to perform
this vital function until birth, they must be
well developed so that they are capable of
functioning as soon as the baby is born.
 At
the beginning of the alveolar period, each
respiratory bronchiole terminates in a cluster
of thin walled terminal sacs separated from
one another by loose connective tissue.
 These terminal sacs represent future alveolar
ducts.
 Characteristic mature alveoli do not form
until after birth.
 Before birth the immature alveoli appear as
small bulges on the walls of respiratory
bronchioles and terminal sacs(future alveolar
ducts).
 After
birth the primitive alveoli enlarge as
the lungs expand, but most increase in the
size of the lungs results from an increase in
number of respiratory bronchioles and
primitive alveoli rather than from an
increase in the size of the alveoli(Crelin,
1975).
 From
the 3rd-8th year or so, the number of
immature alveoli continues to
increase(Thurlbeck, 1991).
 Unlike mature alveoli immature alveoli have
the potential for forming additional primitive
alveoli.
 As primitive alveoli increase in size, they
become mature alveoli.
 Breathing movements occur before birth,
exerting sufficient force to cause aspiration
of amniotic fluid into the lungs.
 These
prenatal breathing movements, which
can be detected by real time
ultrasonography, are not continuous but they
are essential for normal fetal lung
development.
 The pattern of fetal breathing movements is
widely used in the diagnosis of labor and as a
predictor of fetal outcome in preterm
delivery.
 Fetal
breathing movements, which increase
as the time of delivery approaches, probably
condition the respiratory muscles.
 In addition, these movements stimulate lung
development, possibly by creating a pressure
gradient between the lungs and the amniotic
fluid(Behrman, 1992).
 At
birth the lungs are about half filled with
fluid derived from the amniotic cavity, lungs
and tracheal glands.
 Aeration of the lungs at birth is not so much
the inflation of empty collapsed organs but
rather the rapid replacement of intra
alveolar fluid by air.
 The fluid in the lungs is cleared at birth by
three routes:
 Through the mouth and nose by pressure on
the thorax during delivery
 Into
the pulmonary capillaries and into the
lymphatics and pulmonary arteries and veins.
 Respiratory
distress syndrome, infants born
prematurely are susceptible to RDS(Chernick
and Kryger, 1990).
 These infants develop rapid, labored
breathing shortly after birth.
 Hyaline membrane disease is a major cause
of RDS in newborn infants(Behrman, 1992).