Organogenesis

  • The respiratory system develops from the endoderm (lining of the airways and alveoli) and splanchnic mesoderm (connective tissue, cartilage, smooth muscle, and blood vessels).

  • During the third week of gestation, a groove in the primitive foregut originates, and, by week 4, the primordial single lung bud bifurcates. 1

2. Stages of Lung Development

Lung development is classically divided into five overlapping stages:

a. Embryonic Stage (Weeks 4–7)

  • Formation of the respiratory diverticulum (lung bud) from the ventral foregut.

  • Tracheoesophageal septum separates the trachea from the esophagus

  • During weeks 5-6, the primary bronchi continue to elongate and divide, right and left main bronchi, then into lobar bronchi (3 on right, 2 on left).

b. Pseudoglandular Stage (Weeks 5–17)

  • Extensive branching morphogenesis produces terminal bronchioles.

  • Histologically resembles a gland, hence the name.

  • No respiratory bronchioles or alveoli yet → no gas exchange possible.

c. Canalicular Stage (Weeks 16–25)

  • Respiratory bronchioles appear.

  • Differentiation of epithelium into ciliated cells and secretory cells.

  • Vascularization increases; pulmonary capillaries grow closer to airway epithelium.

  • Primitive alveolar regions start forming.

  • Type II pneumocytes begin to appear (~20–22 weeks), producing surfactant (critical for reducing alveolar surface tension).

    Functional gas exchange becomes possible in the late canalicular to saccular stage, with alveolarization continuing into childhood.

d. Saccular Stage (Weeks 24–birth)

  • Terminal sacs (primitive alveoli) form.

  • Thinning of epithelial lining and close apposition with capillaries allows gas exchange.

  • Surfactant production increases significantly around week 26 onward, reaching adequate levels for survival by ~32–34 weeks.

e. Alveolar Stage (Late fetal period to ~8 years)

  • True alveoli form by secondary septation.

  • At birth, only ~20–30 million alveoli are present; number increases to ~300–400 million in childhood.

  • Postnatal lung growth occurs mainly by increasing the number of alveoli.

3. Molecular Regulation

  • FGF-10 (from mesoderm) → promotes bud outgrowth.

  • BMP, SHH, Wnt, HOX genes → regulate branching morphogenesis.

  • VEGF → vascularization of lung tissue.

4. Maturation and Clinical Correlation

  • Adequate surfactant production (by type II pneumocytes) is critical for neonatal survival.

  • Infants born before 26 weeks face severe problems with gas exchange due to immature lungs.

  • Respiratory Distress Syndrome (RDS) is caused by surfactant deficiency, common in preterm infants.

  • Maternal corticosteroids can accelerate fetal lung maturation if preterm birth is anticipated.

 

 

 

Image not available.

Early lung development in a 32-day fetus. From deMello and Reid. Pediat Develop Path. 2000;3:439-449.

 

Respiratory System

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