Development of Organs

...

dwarfism- short limbs and normal trunk.

Development of the Lung

General Anatomy

- The respiratory system is made up of upper and lower parts. The upper part consists of the mouse, nasal passages, pharynx and larynx; the lower part consists of trachea. main bronchus, lobular and segmental bronchi, conducting bronchi, terminal bronchi, respiratory bronchi, alveolar ducts and sacs.

- Gas exchange occurs within the alveoli where oxygen and carbon dioxide diffuse through the capillary endothelium and alveoli epithelium.

- The left and right lung are anatomically different: the left lung has 2 fissures (horizontal and oblique) and 3 lobes whereas the right lung has 1 fissure and 2 lobes. They are separately sealed so injury to one doesn’t affect the functioning of the other.

- The lung is a derived from the mesoderm whereas the trachea and bronchi are derived from endoderm.

- The lung is lined by the visceral and parietal pleura: the former lines the outermost layer of the lung; the later adheres the body cavity.

- A very small volume of pleural fluid lies in the intrapleural space to reduce friction.

- The intrapleural space has sub-atmospheric pressure at rest owing to the elastic recoil of the lung and rigidity of the rib cage, which keeps the lungs expanded.

Histology

- Lung develops from endoderm and surrounding mesenchyme.

- Non- regenerative.

- Progressive disappearance of hyaline cartilage in the walls of reparatory tree with finer and smaller branches.

- Smooth muscles are prominent in bronchioles but no cartilage.

- Elastic fibres are found throughout alveolar wall (NOT in alveolar epithelium). They maintain alveolar shape during contraction and dilation known as elastic recoil. They are produced in fibroblasts that are numerous in alveolar septa.

- 2 layers of pleura comprise of mesothelium and underlying fibre connective tissue with lots of elastin and blood vessels.

- Blood-air barrier: Type I gas exchange alveolar cells and their underlying basal lamina are fused with capillary endothelium.

- Type 2 surfactant alveolar cells and macrophages along with Type I cells make up alveolar epithelium.

- Epithelium of trachea and bronchi is ciliated pseudostratified. They are mucociliary escalator trapping debris via goblet cells (secretions from the seromucous glands in the lamina propria under the epithelium also contributes).

- Epithelium gradually becomes simple columnar then cuboidal in bronchioles and when we reach alveolar cells they become simple squamous.

- Goblet cells disappear by the time we reach terminal bronchioles. No smooth muscle in alveoli.

Development

- There 5 stages of human lung developments: embryonic, pseudo glandular, canalicular, saccular and alveolar.

- The embryonic stage occurs during 4-7 weeks of gestation. Initially, a mid ventral groove appears in a single foregut tube (foregut endoderm).The groove fuses, deepens and constricts at the caudal end to form a respiratory diverticulum ventrally and the oesophagus dorsally. The primitive trachea is formed as the diverticulum elongates caudally.

- The trachea then branches into to bronchial lung buds. Each bud then divides to form the lobular bronchus. Hence, the lung grows by repeated branching at distal end of the lung “tubes”. This process is known as branching morphogenesis.

- Lung bud formation and branching morphogenesis are dependent upon interactions between endoderm (epithelium) of the tubules and surrounding mesenchyme.

- The major growth factors involved in branching morphogenesis are Shh and FGF and the major transcription factors involved are hepatocyte nuclear factor (HNF-3b), Hox and Gli genes and thyroid transcription factor (TTF-1).

- All major structures and lobes are formed during embryonic stage and pulmonary vascular development also occurs simultaneously.

- The psudoglandular stage occurs during 5-17 weeks of gestation. Now, the lung has a branched, tubular, gland-like appearance. However, gas exchange is not possible due to large distance between “air spaces” and blood vessels.

- Branching of the epithelial buds lead to formation of the terminal (conducting) bronchioles, the entire conducting zone is formed.

- Endodermal epithelial cells start to differentiate into ciliated, non-ciliated, goblet and basal cells.

- Mesenchymal cells in the walls of the bronchi begin to form cartilage in conductive airways and smooth muscle cells.

- The canalicular stage occurs during 16-26 weeks of gestation. Canalisation takes place, which is the expansion of “air spaces” by repeated subdivision of tubules. Babies can be born at 23 weeks but will require intensive care. There is still stick a great deal of interstitial tissue (mesenchymal tissue between air spaces) between vessels and air spaces although greatly reduced compared to pseudoglandular stage. Limited gas exchange capacity.

- Airway branching is complete with the appearance of reparatory bronchioles.

- There is increased vascularisation in the lung mesenchyme regulated by vascular endothelial growth factor (VEGF) and hypoxia-induced factor (HIFs).

- Distal lung epithelium begins to differentiate into Type I and Type II cells.

- The saccular stage occurs during 24-26 weeks of gestation until term. There is a decrease in interstitial tissue but stick thick, although gas exchange is now possible.

- The future alveolar ducts and sacs are produced by the formation of secondary septa. As a result, there is a progressive increase in surface area for gas exchange.

- Surfactant secretion occurs.

- Type I cells move closer to the capillaries, basement membranes fuse to allow for efficient gas exchange.

- The