27

Chapter 5
The respiratory system

smooth muscle and blood vessels of the lower respiratory

Development of the respiratory system 27
tract. The respiratory diverticulum develops at the junction
between the cranial and caudal foregut. This diverticulum
Development of the respiratory system soon separates from the foregut by the development of
bilateral longitudinal ridges, the tracheo-oesophageal folds,
The epithelial component of the respiratory system that fuse together to form the tracheo-oesophageal
(including that of the larynx, trachea, bronchi and lungs) septum. This septum separates the ventral trachea from
develops from the ventral wall of the endodermal lining of the dorsal oesophagus (Fig. 5.1B). Thus, the pharynx
the foregut as an outpouching, which grows into the communicates with the larynx via the future laryngeal inlet.
surrounding splanchnopleuric mesoderm as primitive The larynx is lined by epithelium derived from the
connective tissue surrounding the endodermal respiratory endoderm, whereas the cartilages and muscles of the larynx
diverticulum (Fig. 5.1A). The same splanchnopleuric arise from the fourth and sixth pharyngeal arches (see
mesoderm also gives rise to the visceral pleura, cartilage, Chapter 11).
The lung buds are the paired structures that develop
from a single midline outpouching, the respiratory
diverticulum (Fig. 5.1A). Each lung bud divides many times
Pharyngeal to form the bronchial tree. The process by which the
foregut
division of the airways is accomplished is known as
branching morphogenesis and it is regulated by a variety
of molecular signals. There are differences on the two sides:
the right lung bud divides into three secondary bronchial
buds, forerunners of the three lobes, whereas the left lung
bud gives rise to two secondary bronchial buds, to become
Respiratory the two lobes on the left. Thus, a series of rapid further
diverticulum divisions of the airways takes place, penetrating the
surrounding splanchnopleuric mesoderm and bulging
Trachea into the coelomic cavity at the pericardioperitoneal canals
(Chapter 3). These two canals are destined to become the
right and left pleural cavities, and they lie on either side of
the foregut (Fig. 5.2). The pericardial cavity (see Chapter 6)
is separated from the primitive pleural cavities by the
pleuropericardial folds on each side. The peritoneal cavity is
Lung buds separated from the pleural cavities by the pleuroperitoneal
membranes (see Chapter 3). Whilst the splanchnopleuric
A mesoderm forms the visceral layer of the pleura, the
somatopleuric mesoderm lines the thoracic walls and thus
Tracheo-oesophageal Tracheo-oesophageal Oesophagus forms the somatic layers of the pleura.
folds septum Further divisions of the bronchial tree continue but are
Pharynx Trachea not completed until after birth. Indeed, full lung maturation
is not reached until about 6–7 years of age, and new alveoli
continue to be formed up until 10 years of age. Although
the earliest stages of the respiratory tract arise in the
cervical region of the embryo, as the lungs form they
migrate caudally and by the time of birth the tracheal
bifurcation lies opposite the fourth thoracic vertebra.
Respiratory The maturation of the lungs occurs in phases. These
diverticulum
different phases are not important other than to appreciate
B the changes which the lungs undergo. Initially, the lungs
Fig. 5.1 (A) The origin of the respiratory diverticulum from the foregut in a are glandular structures histologically, but over time the
4-week embryo. (B) Transverse sections showing the formation of the epithelium thins and tubes or canals form. This is followed
tracheo-oesophageal septum. by the development of primitive alveoli (Fig. 5.3).
28 EMBRYOLOGY

Lateral plate Peritoneal Respiratory Columnar Terminal Mesenchyme Terminal

splanchnopleure cavity bronchiole epithelium bronchiole sacs

6 weeks
Trachea

Foregut

Visceral
pleura

Pericardio-
peritoneal
canal A 25–36 weeks

Alveolus Capillary Squamous

Pericardial epithelium
cavity

Fig. 5.2 Lung buds growing into the pericardioperitoneal canals

lying on either side of the foregut in a 6-week embryo, with
surrounding tissues removed.

Clinical box
A number of malformations can arise
because of incomplete separation of the
B Birth–childhood
oesophagus and the trachea (Fig. 5.4). The danger of such
malformations in an infant is that swallowed fluids could Fig. 5.3 Histogenesis of the lungs showing thinning of the
enter the respiratory tract. The oesophagus can end epithelium and formation of the blood-air barrier. (A) 25–36 weeks.
(B) Birth–childhood.
blindly and not continue with the distal gut tube, leaving
a connection with the respiratory tract and the distal
gut tube. This is known as a tracheo-oesophageal fistula
and is usually associated with oesophageal atresia.
This leads to abnormal circulation of the amniotic fluid
because the fetus normally swallows the fluid and
it expels the same volume into its urine. In the Trachea Blind-ended
presence of a tracheo-oesophageal fistula, the volume oesophagus
of amniotic fluid increases within the amniotic sac,
polyhydramnios, and an enlarged uterus results. The
affected oesophagus may be surgically re-attached to the
distal gut tube. These abnormalities arise because of
the failure of the tracheo-oesophageal septum to form
properly. If the division of the lung buds fails to occur
properly the lungs will be smaller than normal, a
condition known as pulmonary hypoplasia. Unilateral Oesophagus
agenesis is also possible so that the lung fails to form on Fistula
one side.
Failure of the type II alveolar cells to produce
surfactant results in respiratory distress syndrome
seen in premature infants. Without surfactant the lungs
do not inflate properly, alveoli collapse and respiratory
distress results.
Fig. 5.4 Types of tracheo-oesophageal fistulae.
 The Respiratory System 29

Respiration is not possible until the cuboidal epithelium of After birth there is a dramatic and rapid change in the
the canals has thinned sufficiently. During this period lungs to enable air breathing to take place. Prior to birth
capillaries come into contact with the thinning epithelial there is a large volume of fluid in the lungs, which needs to
wall and establish the possibility of respiratory gaseous be removed to allow air to pass into the lungs. A number
exchange. This begins from about the seventh month. The of mechanisms facilitate this process. A large volume of the
cells lining the sacs become the alveolar type I cells. Type II fluid is removed through absorption by the blood capillaries
surfactant-producing cells appear from about 6 months of and lymphatics of the lungs, assisted by the thinning of the
age. Surfactant, a phospholipid, reduces the surface epithelium. The pressure of the birth canal itself also helps
tension at the air–fluid interface in the alveoli and this helps by squeezing the chest wall to expel fluid.
the air spaces to inflate.

Summary box
■ The respiratory system develops from two germ layers. The ■ Mature alveoli continue to develop until 6 or 7 years of age. Lung
epithelial lining arises from the endoderm, which forms the lining development passes though a number of phases: from an initial
of the foregut tube. glandular stage to a tubular phase, resulting in formation of the
■ A small diverticulum buds off the ventral surface of the foregut to airway tubes.
form the lung bud. This grows into the splanchnopleuric ■ After 26 weeks of fetal life the lining of the alveoli thins from a
mesoderm, enlarging and bulging into the future cuboidal to a simple squamous epithelium, thereby facilitating
pericardioperitoneal canals. These two components of the intra- gaseous exchange.
embryonic coelom become the pleural cavities. ■ It is not until after this time that air-breathing is possible, and is a
■ The lung buds divide rapidly by a process known as branching reason why premature infants younger than 26 weeks are often
morphogenesis regulated by a variety of molecular signals. There non-viable.
is, however, an asymmetry in this division such that the left lung ■ Type I alveolar cells line the walls of the alveoli; type II alveolar cells
has two lobes and the right lung has three. produce surfactant, a phospholipid material which reduces the
■ The cartilage and smooth muscle of the airways and visceral pleura surface tension of the fluid in the lungs. This helps prevent collapse
develop from the surrounding splanchnopleuric mesoderm. The of the alveolar spaces. Infants in whom type II alveolar cells do
somatopleuric mesoderm lines the future thoracic wall, as parietal not produce surfactant may suffer from respiratory distress
pleura. syndrome.