4. Respiratory Embryology (Dennis) Flashcards
structures during early development of the respiratory system
The embryonic phase takes place between the third and sixth week of gestation. The development of the lungs begins during the third week, with the appearance of a respiratory diverticulum (lung bud) as an outgrowth from the ventral wall of the foregut.
The lung bud expands in a ventral and caudal direction, invading the mesenchyme surrounding the foregut. Soon after, the lung bud being initially in open communication with the foregut, becomes separated from it eventually forms the esophagus.
Larynx development
The distal end of the lung bud bifurcates into the right and left primary bronchial buds, whereas the proximal end (stem) forms the trachea and larynx. By the fifth week of gestation, the primary bronchial buds form three secondary bronchial buds on the right side and two on the left, foreshadowing the primordial lobes of the lungs. Each secondary bronchial bud gives rise to ten tertiary bronchial buds on both sides, demarcating the end of the embryonic phase.
Tissue origin on the larynx
The internal lining of the larynx originates from endoderm, but the cartilages and muscles originate from mesenchyme of the fourth and sixth pharyngeal arches.
Laryngeal orifice
As a result of rapid proliferation of this mesenchyme, the laryngeal orifice changes in appearance from a sagittal slit to a T-shaped opening. When the mesenchyme of the two arches transforms into the thyroid, cricoid and arytenoid cartilages the adult shape of the laryngeal orifice can be recognized. The laryngeal epithelium proliferates rapidly, resulting in a temporary occlusion of the lumen. Subsequently, vacuolization and recanalization produces a pair of lateral recesses, the laryngeal ventricles that are bounded by folds of tissue that differentiate into the false and true vocal cords
Innervation of the larynx
Since musculature of the larynx is derived from mesenchyme of the fourth and sixth pharyngeal arches, all laryngeal muscles are innervated by branches of vagus nerve (the superior laryngeal nerve innervates derivatives of the fourth pharyngeal arch and the recurrent nerve innervates derivatives of the sixth laryngeal arch).
Endodermal and mesodermal components of the trachea
- tracheal epithelium and glands are derived from endoderm
- tracheal smooth muscle, connective tissue, and cartilage are derived from visceral (or splanchnic) mesoderm.
- as with the larynx, the endoderm overproliferates resulting in occlusion of the lumen followed by recanalization by about 10 weeks.
tracheoesophageal septum
As the respiratory diverticulum grows, longitudinal mesodermal folds called the tracheo-esophageal ridges form that eventually pinch off to separate the trachea from the esophagus. This process is driven by
- retinoid acid signaling
- TBX4 expression in the endoderm
- causing disruption of the mesoderm.
Tracheo-esophegeal fistulas
Tracheoesophageal fistulas occur in about 1 in 3000 births and most are of the sort where the proximal esophagus ends blindly whereas the distal esophagus communicates with the trachea via a fistula. Complications arise both prenatally and postnatally:
PRENATALLY: polyhydramnios (too much amniotic fluid) due to an inability of the fetus to swallow the amniotic fluid (an important part of the recycling the fluid)
POSTNATALLY: infants cough and choke IMMEDIATELY upon feeding due to an inability to swallow; connection of lower esophagus to the trachea can allow gastric contents to get into lungs causing irritation and possibly pneumonitis (inflammation of the lungs).
Often associated with a spectrum of mesodermal defects called the VATER association (Vertebral anomalies, Anal atresia, Tracheoesophageal fistula, Esophageal atresia, and Renal atresia), or, if Cardiac defects and Limb defects are also present, VACTERL.
Pseudoglandular phase of respiratory development
takes place during between the sixth and sixteenth (6-16) week of gestation. The respiratory tree undergoes twelve to fourteen more generations of branching, resulting in the formation of terminal bronchioles. This passageway will be lined with a specific type of respiratory epithelium, simple columnar epithelium (ciliated) transitioning to simple cuboidal epithelium (some cilia).
Canalicular phase of lung development
takes place during the sixteenth and twenty-eighth (16-28) week of gestation. Each terminal bronchioles further divide into respiratory bronchioles, which become surrounded with an increase in vascularization. Subsequently, the lumens of the respiratory bronchioles become enlarged as a result of the thinning of their epithelial walls. This process sets up the differentiation of specialized cell types associated with the lungs.
Saccular phase of lung development
takes place between the twenty-eighth and thirty-sixth (28-36) week of gestation. The respiratory bronchioles give rise to a final generation of terminal branches. These branches become invested in a dense network of capillaries, forming the terminal sacs (primitive alveoli) that are lined with type I and type II alveolar cells.
Alveolar phase of lung development
characterized by the maturation of the alveoli, a process that takes place during the end of fetal life and many years after birth.
Role of surfactant
Pulmonary surfactant or simply surfactant (surface active agent) begins to be produced at the canalicular stage and both production and turnover are key for development. It is a mixture of lipids and proteins secreted by Type 2 alveolar cells between alveolar epithelium that reduces surface tension (detergent) at the air-liquid interface. The function of this secretion is to prevent collapse of the lung at the end of expiration. In humans, these cells and their secretion develop towards the very end of the third trimester, just before birth.
Type II alveolar cells
act as the ‘caretaker’ by responding to damage of the type I cells. Type II alveolar cells do this by dividing and acting as a progenitor cell for both type I and type II cells.
In addition, they synthesise, store and release pulmonary surfactant into the alveolar hypophase, where it acts to optimise conditions for gas exchange
Esophageal atresia (EA)
is characterized by a blind-ended closure of either the proximal part, distal part, or both parts of the esophagus.
