The respiratory system begins to develop during the fourth week of gestation from the foregut endoderm and surrounding splanchnic mesoderm . Until birth, maternal-placental circulation provides all fetal oxygen and removes carbon dioxide.
Origin
- Derived from the primitive foregut , an endodermal structure formed during lateral folding of the embryo.
- The respiratory diverticulum (lung bud) forms as a ventral outpouching of the foregut around week 4 , under the influence of fibroblast growth factor (FGF) signaling from surrounding mesenchyme.
Developmental Stages
Formation of Lung Buds
- Arises from ventral foregut .
- Initial open communication with foregut.
- Tracheoesophageal ridges develop and fuse to form the tracheoesophageal septum , separating:
- Dorsal esophagus
- Ventral trachea and lung buds
The epithelium of the trachea, bronchi, and lungs is of endodermal origin , while the cartilage, smooth muscle, and connective tissue are derived from splanchnic mesoderm .
Partitioning Defects
Improper septum formation may cause:
Esophageal Atresia (EA) and Tracheoesophageal Fistula (TEF)
- Occur in ~1/3,000 births.
- Most common type: Proximal esophageal atresia + distal TEF (90%).
- Associated anomalies: VACTERL association:
- V ertebral anomalies
- A nal atresia
- C ardiac defects
- TE F
- E sophageal atresia
- R enal anomalies
- L imb defects
Polyhydramnios may develop due to impaired swallowing, and aspiration pneumonia can occur due to reflux through fistulas.
Larynx Development
- Epithelium from endoderm .
- Cartilages and muscles from mesenchyme of the 4th and 6th pharyngeal arches .
- Early on: Sagittal slit → later forms T-shaped opening .
- Thyroid, cricoid, and arytenoid cartilages form from mesenchyme.
- Lumen is temporarily obliterated by epithelial overgrowth but later reopens via vacuolization and recanalization , forming laryngeal ventricles , true and false vocal cords .
Trachea, Bronchi, and Lung Formation
Branching Morphogenesis
- Week 5 : Bronchial buds → primary bronchi (right and left).
- Right: 3 secondary bronchi (3 lobes)
- Left: 2 secondary bronchi (2 lobes)
- Further branching → 10 segmental bronchi on right, 8 on left → form bronchopulmonary segments .
- FGF10 signaling from mesenchyme controls branching.
🫁 Bronchi develop as endoderm-mesoderm interactions , forming a complex 3D airway tree.
Pleural Development
- Lung buds grow into pericardioperitoneal canals , later forming pleural cavities .
- Visceral pleura from splanchnic mesoderm
- Parietal pleura from somatic mesoderm
- Pleural cavity : space between these layers
Lung Maturation Stages
| Period | Weeks | Key Features |
|---|---|---|
| Pseudoglandular | 5–16 weeks | Branching → terminal bronchioles; no gas exchange |
| Canalicular | 16–26 weeks | Formation of respiratory bronchioles , alveolar ducts , and vascularization |
| Terminal Sac | 26 weeks–birth | Primitive alveoli (terminal sacs) and capillary proximity allow gas exchange |
| Alveolar | 8 months–childhood | Development of mature alveoli and surfactant production |
By week 26 , sufficient terminal sacs and type I pneumocytes allow preterm survival with support.
Surfactant Production
- Type II pneumocytes begin surfactant synthesis at ~ week 24 .
- Significant increase in production occurs in the last 2 weeks of gestation.
- Surfactant :
- Rich in phosphatidylcholine (lecithin)
- Reduces alveolar surface tension
- Prevents alveolar collapse during exhalation
Fetal Lung Fluid
- Prior to birth, lungs are filled with fluid containing:
- Chloride
- Minimal protein
- Mucus
- Surfactant
- Fetal breathing movements occur in utero to promote lung growth and amniotic fluid aspiration.
High-Yield Points
- Lung buds form from the endodermal foregut around week 4 .
- TEF + EA are common congenital malformations; always consider VACTERL association.
- Surfactant production begins ~ week 24 , but surfactant surge occurs at ~week 34–36 .
- Mature alveoli continue developing into early childhood (~8 years).
- Lung branching is driven by FGF10 signaling from mesenchyme.
- Tracheoesophageal septum divides respiratory and digestive tracts.
