Development of Lungs

1. Origin and Initial Formation

2. Bronchial Branching

• By the 5th week, primary bronchial buds enlarge to form the main (primary) bronchi.
• These subdivide into secondary (lobar) bronchi: 3 on the right (for upper, middle, and lower lobes) and 2 on the left (upper and lower lobes).
• Further branching produces segmental (tertiary) bronchi: 10 on the right, 8-9 on the left, beginning by the 7th week. Each segmental bronchus with surrounding mesenchyme forms a bronchopulmonary segment.
• By 24 weeks, approximately 17 orders of branches have formed, with respiratory bronchioles present. Seven additional orders develop postnatally.

3. Maturation Stages of the Lung (4 Overlapping Stages)

A. Pseudoglandular Stage (5-17 weeks)

• The developing lung resembles an exocrine gland histologically.
• All major elements form except those involved in gas exchange.
• Respiration is not possible; a fetus born at this stage cannot survive.

B. Canalicular Stage (16-25 weeks)

• Lumina of bronchi and terminal bronchioles enlarge; lung becomes highly vascular.
• By 24 weeks, terminal bronchioles branch into 2+ respiratory bronchioles, each forming 3-6 primordial alveolar ducts.
• By 26 weeks, limited respiration is possible due to thin-walled terminal sacs and vascularization - premature survival is possible with intensive care.

C. Terminal Sac (Saccular) Stage (24 weeks - late fetal period)

• Many terminal sacs (primordial alveoli) develop with very thin epithelium.
• Capillaries bulge into sacs, forming the blood-air barrier.
• The sacs are lined by two cell types (both of endodermal origin):
  • Type I pneumocytes (squamous) - for gas exchange
  • Type II pneumocytes (rounded/secretory) - produce pulmonary surfactant (phospholipids + proteins)
• Surfactant begins at ~20-22 weeks but reaches adequate levels only by the late fetal period.
• By 26-28 weeks (~1000 g fetus), sufficient alveoli and surfactant allow premature survival.
• Antenatal corticosteroids induce surfactant production; postnatal surfactant replacement therapy is used for deficiency.

D. Alveolar Stage (Late fetal period - 8 years)

• By 32 weeks, terminal sacs analogous to mature alveoli are present.
• Type I pneumocytes become extremely thin; capillaries bulge into alveolar sacs forming the alveolocapillary (respiratory) membrane.
• By 38 weeks (late fetal), gas exchange is fully possible.
• At birth: ~150 million primordial alveoli (half the adult number).
• By 3 years: alveolar development largely complete.
• By 8 years: adult complement of ~300 million alveoli achieved.
• 95% of mature alveoli develop postnatally.

4. Pleura Formation

• Visceral pleura derives from splanchnic (visceral) mesoderm surrounding the lung buds.
• Parietal pleura derives from somatic (parietal) mesoderm lining the body wall.
• The pleural cavity is the space between these two layers.

5. Molecular Regulation

• Transcription factors: TTF-1 (thyroid transcription factor-1), HNF-3β, GATA-6.
• FGF10 from splanchnic mesenchyme induces respiratory bud formation.
• Wnt signaling (including Wnt7b) drives epithelial-mesenchymal interaction for branching morphogenesis.
• Sonic hedgehog (Shh) modulates FGF10 and controls bronchial bud branching and smooth muscle differentiation.
• Retinoic acid regulates Hox genes (a5, b5, c4) in the developing lung.

6. Fetal Breathing Movements (FBMs)

Key Clinical Points