medicine

1. Development of respiratory
system

2. • The lower respiratory organs(larynx, trachea, bronchi, and
lungs) begin to form during the 4th wk of development
– starts as a median outgrowth (laryngotracheal groove) that appears
in the floor of caudal end of primordial pharynx
• Primordium of tracheobronchial tree develops caudal to 4th
pair of pharyngeal pouches
• Endodermal lining of laryngotracheal groove gives rise to
pulmonary epithelium & glands of larynx, trachea,& bronchi
• Connective tissue, cartilage, & smooth muscle in these
structures develop from splanchnic mesoderm surrounding
foregut
Introduction

3. A, Sagittal section
of the cranial half of
a 4-week embryo.
B,Horizontal section of
the embryo, illustrating
the floor of primordial
pharynx and location of
laryngotracheal groove.

4. • By the end of 4th wk, laryngotracheal groove has evaginated
(protruded) to form a pouch-like laryngotracheal
diverticulum (lung bud), which is located ventral to the
caudal part of the foregut
• As the diverticulum elongates, its distal end enlarges to
form a globular respiratory bud
• laryngotracheal diverticulum soon separates from
primordial pharynx, but it maintains communication with it
through the primordial laryngeal inlet
Introduction…

5. • Longitudinal tracheoesophageal folds develop in the
laryngotracheal diverticulum
– this fold approach each other and fuse to form a partition called
tracheoesophageal septum
• The septum divides cranial part of foregut into:
– ventral part (laryngotracheal tube ) which is the primordium of
larynx, trachea, bronchi, and lungs
– dorsal part which is primordium of oropharynx & esophagus.
• The opening of laryngotracheal tube into the pharynx
becomes the primordial laryngeal inlet
Introduction…

6. Successive stages in the development of tracheoesophageal septum
during 4th & 5th wks of development. A to C, Lateral views of the caudal
part of primordial pharynx, showing laryngotracheal diverticulum &
partitioning of foregut into esophagus & the laryngotracheal tube. D to
F,Transverse sections, formation of tracheoesophageal septum.

7. Transverse sections showing the formation of
the tracheo-oesophageal septum

8. • A number of malformations can arise because of incomplete
separation of the oesophagus and the trachea.
• The danger of such malformations in an infant is that
swallowed fluids could enter the respiratory tract.
• The oesophagus can end blindly and not continue with the
distal gut tube, leaving a connection with the respiratory tract
and the distal gut tube.
– known as a tracheo-oesophageal fistula and is usually associated
with oesophageal atresia.
Complication of TEF
• Pneumonia or pneumonitis
• Polyhydramnios( why???)
Tracheoesophageal fistula

9. Four main varieties TEF are shown in order of frequency
A,Esophageal
atresia is
associated
with TEF in
more than
85% of cases
B,Fistula b/n the
trachea and
esophagus( 4%)
C, Atresia of proximal esophagus ending in a TEF with distal
esophagus having a blind pouch. D, Atresia of proximal segment of
esophagus with fistulas b/n trachea and both proximal and distal
segments of esophagus

10. • Epithelial lining of larynx develops from the endoderm of
cranial end of laryngotracheal tube
• Cartilages of larynx develop from 4th & 6th pairs of
pharyngeal arches
– from mesenchyme that is derived from neural crest cells
• Laryngeal muscles develop from myoblasts in the 4th & 6th
pairs of pharyngeal arches
– are therefore innervated by laryngeal branches of CN X
Development of larynx

11. Successive stages in the development of larynx. A,4 wks. B,5 wks. C,6
wks. D,10 wks. Note that the laryngeal inlet changes in shape from a
slit-like opening to a T-shaped inlet as the mesenchyme surrounding the
developing larynx proliferates

12. • Develop from laryngotracheal tube distal to larynx
– endodermal lining differentiates into epithelium & glands of
trachea and pulmonary epithelium.
– cartilage, connective tissue, & muscles of trachea are derived
from splanchnic mesoderm surrounding laryngotracheal tube
Development of trachea
Transverse sections through the
laryngotracheal tube, progressive
stages in the development of trachea.
A,4 weeks. B,10 weeks. C,11 weeks

13. • The respiratory bud (lung bud) develops at the caudal end
of the laryngotracheal diverticulum during the 4th wk.
• The bud soon divides into two outpouchings (primary
bronchial buds).
• Later, secondary and tertiary bronchial buds form and
grow laterally into the pericardioperitoneal canals
Development of bronchi and lungs

14. Illustrations of the growth of the developing lungs into splanchnic
mesoderm adjacent to the medial walls of the pericardioperitoneal
canals (primordial pleural cavities). Development of the layers of
the pleura is also shown. A,5 weeks. B,6 weeks

16. • Together with the surrounding splanchnic mesoderm, the
bronchial buds differentiate into the bronchi and their
ramifications in the lungs.
• Early in the 5th wk, the connection of each bronchial bud
with trachea enlarges to form primordia of main bronchi.
– The embryonic right main bronchus is slightly larger than the left
one and is oriented more vertically.(ADULT???)
Development of bronchi and lungs…

17. • The main bronchi subdivide into secondary bronchi that
form lobar, segmental, and intrasegmental branches.
• On the right, the superior secondary bronchus supplies the
upper (superior) lobe of the lung, whereas the inferior
secondary bronchus subdivides into two bronchi (one for
middle & one for lower(inferior)lobe right lung
• On the left, the two secondary bronchi supply the upper and
lower lobes of the lung.
Development of bronchi and lungs…

18. • The segmental bronchi, 10 in the right lung and 8 or 9 in the
left lung, begin to form by the 7th wk.
• As this occurs, the surrounding mesenchyme also divides.
• Each segmental bronchus, with its surrounding mass of
mesenchyme, is the primordium of a bronchopulmonary
segment.
• By 24 wks, approximately 17 orders of branching have
occurred and respiratory bronchioles have developed.
• An additional seven orders of airways develop after birth.
Development of bronchi and lungs…

19. • As the bronchi develop, cartilaginous plates are formed
from the surrounding splanchnic mesenchyme.
– bronchial smooth muscle & connective tissue and pulmonary
connective tissue & capillaries are also derived from this
mesenchyme
• As the lungs develop, they acquire a layer of visceral pleura
from splanchnic mesoderm.
• With expansion, the lungs and 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 the somatic mesoderm.
Development of bronchi and lungs…

20. Successive stages in the development of the bronchial buds, the
bronchi, and the lungs

21. • Maturation of lungs is divided into 4 histologic stages:
– Pseudoglandular
– Canalicular
– Terminal saccular
– Alveolar
Maturation of Lungs

23. • lungs resemble an exocrine
gland during early part of
this period
• By 16 wks, all of the major
elements of the lung have
formed, except those
involved with gas exchange.
• Respiration is not possible;
hence, fetuses born during
this period are unable to
survive
Pseudoglandular Period (5–17 Wks)

24. • This period overlaps the pseudoglandular period b/c
cranial segments of the lungs mature faster than caudal
segments.
• During the canalicular period, the lumina of the bronchi
and the terminal bronchioles become larger and the lung
tissue becomes highly vascular.
• By 24 wks, each terminal bronchiole has given rise to
two or more respiratory bronchioles,
• Each respiratory bronchioles divides into three to six
tubular passages (primordial alveolar ducts).
Canalicular Period (16–25 Weeks)

25. • Respiration is possible
toward the end of the
canalicular stage b/c some
primordial alveoli have
developed & the lung tissue
is well vascularized
• Although a fetus born at 24 to
26 weeks may survive if
given intensive care, it often
dies because its respiratory
and other systems are
relatively immature
Canalicular Period (16–25 Weeks)…

26. • many more terminal sacs (primordial alveoli) develop, and
their epithelium becomes very thin
• Capillaries begin to bulge into these sacs.
• The intimate contact b/n epithelial and endothelial cells,
establishes the blood-air barrier, which permits adequate
gas exchange for survival
• By 26 wks, the terminal sacs are lined mainly by type I
pneumocytes across which gas exchange occurs.
• Scattered among type I pnumocytes are rounded secretory
type II pneumocytes (secret surfactant)
Terminal saccular period(24 wks -late fetal period)

27. • maturation of alveolar type II
cells & production of
surfactant vary widely in
fetuses of different ages.
• Surfactant production begins
by 20-22 wks, but surfactant
is present in only small
amounts in premature infants.
– It does not reach adequate
levels until the late fetal
period.
Terminal saccular period…

28. • At the beginning of the
alveolar period, each
respiratory bronchiole
terminates in a cluster of
thin-walled terminal sacs
that are separated from one
another by loose connective
tissue.
– These terminal sacs represent
future alveolar ducts.
Alveolar Period (Late Fetal Period to 8 Years)

29. • alveolocapillary membrane (respiratory membrane) is
sufficiently thin to allow gas exchange.
• transition from dependence on placenta for gas exchange
to autonomous gas exchange after birth requires the
following adaptive changes in the lungs:
– Production of surfactant in the alveolar sacs
– Transformation of the lungs into gas-exchanging organs
– Establishment of parallel pulmonary and systemic circulations
Alveolar Period…

30. • Approximately 95% of mature alveoli develop in the
postnatal period.
• Before birth, the primordial alveoli appear as small bulges on
the walls of the respiratory bronchioles & alveolar sacs
• After birth, the primordial alveoli enlarge as the lungs expand
• increase in the size of the lungs results mainly from a
continued increase in the number of respiratory
bronchioles and primordial alveoli
Alveolar Period…

31. • Alveolar development is largely complete by 3 years of age,
but new alveoli may be added until approximately 8 years of
age
• Approximately 150 million primordial alveoli, one half the
number in adults, are present in the lungs of fullterm neonates.
• B/n the 3rd & 8th year, the adult complement of 300 million
alveoli is achieved
• Three factors that are essential for normal lung development
are:
– Adequate thoracic space for lung growth
– Adequate amniotic fluid volume
– Fetal breathing movements
Alveolar Period…

32. • Fetal breathing movements occur before birth, exerting
sufficient force to cause aspiration of some amniotic fluid
into the lungs.
• These fetal breathing movements occur approximately
50% of the time and only during rapid eye movement
sleep.
– These movements stimulate lung development
• By birth, the fetus has had the advantage of several months
of breathing exercise.
Alveolar Period…

33. • At birth, the lungs are approximately half-filled with fluid
derived from the amniotic cavity, the lungs, and the
tracheal glands.
• The fluid in the lungs is cleared at birth by three routes:
– Through the mouth and nose by pressure on the thorax during
vaginal delivery
– Into the pulmonary capillaries and pulmonary arteries and
veins
– Into the lymphatic vessels
Alveolar Period…

34. Lung hypoplasia
• is characterized by markedly reduced lung volume.
• It usually occurs due to congenital diaphragmatic
hernia(CHD)
• Many infants with CDH die of pulmonary insufficiency b/c
their lungs are too hypoplastic to support extrauterine life
Neonatal respiratory distress syndrome
• Failure of the type II alveolar cells to produce surfactant
results in respiratory distress (hyaline membrane disease) seen
in premature infants
– Without surfactant the lungs do not inflate properly, alveoli collapse
and respiratory distress results.
Abnormality in the development of lung