Embryology of the Respiratory System, Universidad Autónoma De Guadalajara

Objectives of Respiratory System Embryology

1. Formation and development of the lung buds
2. Describe the pathogenesis of esophageal atresia and trachoesophageal fistulas
3. Describe the development of the larynx, trachea, and bronchi
4. Differentiate the origin of the parietal and visceral pleura
5. Outline the process of lung maturation
6. Analize the pathogenesis of Newborn Respiratory Distress Syndrome (NRDS)

Formation of the Lung Buds

When the embryo is approximately 4 weeks old, the respiratory diverticulum (lung bud) appears as an outgrowth from the ventral wall of the foregut.

The appearance of the lung bud are dependent upon increase of retinoic acid (RA) The increase causes upregulation of transcription factor TBX4 TBX4 induces formation of the lung bud

The epithelium of the internal lining of the larynx, trachea and bronchi, as well as the lungs is entirely endodermal origin. The cartilaginous, muscular and connective tissue components of the trachea and lungs are derived from visceral (splanic mesoderm).

Initially, the lung bud is in open communication with the foregut. When the diverticulum expands caudally, the tracheoesophageal ridges, separate it from the foregut.

When these ridges fuse to form the tracheoesophageal septum, the foregut is divided into a dorsal portion, the esophagus, and a ventral portion, the trachea.

The respiratory primordium maintains its communication with the pharynx through the laryngeal orifice.

Esophageal Atresia and Tracheoesophageal Fistulas

Abnormalities in the partitioning of the esophagus and trachea by the tracheoesophageal septum.

Gross classification + Flow of feeds Vogt classification + Flow of air

Larynx Development

The internal lining of the larynx originates from endoderm, but the cartilages and muscles originate from mesenchyme of the fourth and sixth pharyngeal arches.

As a result of rapid proliferation of this mesenchyme, the laryngeal orifice changes in appearance from a sagittal slit to a T-shaped opening.

The laryngeal epithelium proliferates rapidly, resulting in a temporary occlusion of the lumen. Vacuolization and recanalization produce a pair of lateral recesses, the laryngeal ventricles.

These recesses are bounded by folds of tissue that differentiate into the false and true vocal cords.

All laryngeal muscles are innervated by branches of the 10th cranial nerve (vagus).

• The superior laryngeal nerve innervates derivatives of the fourth pharyngeal arch
• The recurrent laryngeal nerve innervates derivatives of the sixth pharyngeal arch

Pharyngeal Arch Derivatives

Table 14.1

ARCH	SKELETAL	LIGAMENTS	MUSCLES	NERVES	VESSELS
FIRST (MANDIBULAR)	Upper portions of the malleus and incus	Anterior ligament of the malleus, sphenomandibular ligament	Muscles of mastication, mylohyoid, anterior belly of the digastric muscle, tensor tympani, tensor palati	Trigeminal (maxillary and mandibular divisions)	Terminal branch of the maxillary artery
SECOND (HYOID)	Lower portion of the malleus and incus, stapes, styloid process of the temporal bone, lesser horns, and upper part of the body of hyoid bone	Stylohyoid ligament	Muscles of facial expression, stapedius, stylohyoid, posterior belly of the digastric muscle	Facial	Stapedial artery
THIRD	Greater horns and lower part of body of hyoid bone	None	Stylopharyngeal	Glossopharyngeal	Common carotid artery, root of internal carotid
FOURTH AND SIXTH	Thyroid cartilage, arytenoid cartilage, corniculate cartilage, cuneiform cartilage, cricoid cartilage	None	Pharyngeal and laryngeal muscles	Vagus (superior laryngeal and recurrent laryngeal arches)	Aortic arch, right subclavia, origin sprouts of the pulmonary arteries, ductus arteriosus, roots of definitive pulmonary arteries

Trachea, Bronchi and Lungs

Trachea Formation

During its separation from the foregut, the lung bud forms the trachea and two lateral outpocketings, the primary bronchial buds.

At the beginning of the fifth week, each of the bronchial buds enlarges to form right and left primary bronchi.

Bronchi Development

The right primary bronchi forms 3 secondary bronchi, and the left, 2. Thus foreshadowing the three lobes of the lung on the right side and two on the left.

Secondary bronchi divide repeatedly forming tertiary (segmental) bronchi creating the bronchopulmonary segments of the adult lung: Right lung: 10 Left lung: 8 By the end of the sixth month, 17 generations of subdivisions have formed.

Pleura Formation

The spaces for the lungs, the pericardioperitoneal canals, are narrow. They lie on each side of the foregut and are gradually filled by the expanding growth of the lungs.

The pleuroperitoneal and pleuropericardial folds separate the pericardioperitoneal canals from the peritoneal and pericardial cavities, respectively, and the remaining spaces form the primitive pleural cavities.

• Visceral peritoneum

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 CAVITY.

Lungs Development

While all of these new subdivisions are occurring and the bronchial tree is developing, the lungs assume a more caudal position, so that by the time of birth, the bifurcation of the trachea (carina) is opposite the fourth thoracic vertebra.

Maturation of the Lungs

By the seventh month, the bronchioles divide continuously into more and smaller canals (canalicular phase) and the vascular supply increases.

Terminal bronchioles divide to form respiratory bronchioles, and each of these divides into 3-6 alveolar ducts that end in terminal sacs (primitive alveoli).

By the end of the seventh month, sufficient numbers of mature alveolar sacs and capillaries are present to guarantee adequate gas exchange, and the premature infant is able to survive.

AT THE END OF THE 6TH MONTH Type I alveolar epithelial cells, cells lining the sacs, 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.

Type II alveolar epithelial cells, produce surfactant, a phospholipid-rich fluid capable of lowering surface tension at the air-alveolar interface.

Lung Maturation Stages

Table 14.1 Maturation of the Lungs

Pseudoglandular period 5-16 wk Branching has continued to form terminal bronchioles. No respiratory bronchioles or alveoli are present.

Canalicular period 16-26 wk Each terminal bronchiole divides into two or more respiratory bronchioles, which in turn divide into three to six alveolar ducts.

Terminal sac period 26 wk to birth Terminal sacs [primitive alveoli] form, and capillaries establish close contact.

Alveolar period 8 mo to childhood Mature alveoli have well-developed epithelial endothelial [capillary] contacts.

Fetal breathing movements begin before birth and cause aspiration of amniotic fluid. These movements are important for stimulating lung development and conditioning respiratory muscles.

When respiration begins at birth, most of the lung fluid is rapidly resorbed by the blood and lymph capillaries, and a small amount is probably expelled via the trachea and bronchi during delivery.

Respiratory movements after birth bring air into the lungs, which expand and fill the pleural cavity.

Although the alveoli increase somewhat in size, growth of the lungs after birth is due primarily to an increase in the number of respiratory bronchioles and alveoli.

It is estimated that only one-sixth of the adult number of alveoli are present at birth. The remaining alveoli are formed during the first 10 years of postnatal life through the continuous formation of new primitive alveoli.