Respiratory Systems 14 - Lung Development in Childhood Flashcards
Briefly summarise the timeline of lung development
- Embryonic phase (0-7 weeks) lung buds/main bronchi
- Pseudoglandular (5-17 weeks) conducting airways, bronchi & bronchioli
- Canalicular (16-27 weeks) respiratory airways and blood gas barrier
- Saccular/alveolar (28-40 weeks) alveoli appear
- Postnatal/ adolescence - alveoli multiply and enlarge in size with chest cavity
How does interaction between airways and pulmonary vessels occur throughout development?
- Vasculogenesis occurs as branching morphogenesis occurs
- Alveo and angiogenesis occur
When do alveoli appear?
- Before birth, though they continue to grow in early childhood
- 1/3 to 1/2 the adult number by term
Describe what occurs in lung development during the pseudoglandular phase.
- Braching morphogenesis of airways into mesenchyme
- Pre-acinar airways all present by 17 weeks
- Development of cartilage, gland and smooth muscle tissue begins
List the factors driving branching morphogenesis
- Lung buds (consistent appearance during airway formation)
- Epithelial cells at the tips of lung buds are highly proliferative multipotent progenitor cells
- Cells behind the tip divide and differentiate into the various cell types
- Communication between epithelial cells in distal branching lung buds and surrounding mesenchyme
List the inductive growth factors in lung development
- FGF (branching morphogenesis, subtypes found in epithelium and mesenchyme)
- EGF (epithelial proliferation and differentiation)
List the inhibitory growth factors in lung development
- TGF beta (matrix synthesis surfactant production, inhibits proliferation of epithelium and blood vessels)
- Retinoic acid (inhibits branching)
Describe the process of endothelial differentiation
- Endothelial cells differentiate in the mesenchyme around the lung bud
- They coalesce to form capillaries in vasculogenesis
- Airways act as structural template
- VEGF produced by epithelial cells stimulates endothelial differentiation
Describe what happens in lung development in the canalicular stage
- Airspaces at the periphery emerge
- Thinning of epithelium by underlying capillaries allows gas exchange
- Blood gas barrier required in post-natal life
- Epithelial differentiation into type I and II cells
- Surfactant first detectable at 24-25 weeks
- Babies become viable at 24 weeks
Describe the mechanism of formation of alveolar walls
- Saccule wall is where there is epithelium on both sides with a double capillary network
- Secondary septa develop from the wall led by elastin produced by myofibroblasts. Capillaries line each side with matrix inbetween
- Capillaries coalesce to form one sheet alveolar wall, thinner and longer. Muscle and elastin are at the tip
Describe the appearance of the lung at birth in man
- Volume is small and related to body weight
- All airways are present and differentiated
- Blood gas barrier present
- 22-50% alveoli (normal gas exchange)
- Most arteries and veins present
List the possible mechanisms to increase flow after birth
- Expansion of aleoli dilates arteries
- Expansion stimulates release of vasodilator agents
- Inhibition of vasoconstrictors present during fetal life
- Direct effect of oxygen on smooth muscle cells
Describe the changes at birth in blood vessels
- Decrease in pulmonary vascular resistance
- 10 fold rise in pulmonary blood flow
- Arterial lumen increases and wall thins rapidly
- Change in cell shape and cytoskeletal organisation (not loss of cells)
- Once thinning has occurred, arteries grow and maintain a relatively thin wall
- Low pressure, low resistance pulmonary vascular system
What is primary ciliary dyskinesia?
- A rare genetic condition where there are no dyenin arms
- This means that cilia are immobile, and there is a build up of mucous
List the issues that may be seen in congenital bronchial cartilage defects
- Incomplete rings posteriorly
- Irregular plates
- Calcify with age
- Generalised (laryngotracheomalacia)
- Localised (malacic segment which may occur due to external compression)
List the types of lung growth anomalies
- Agenesis (complete absence of lung/vessel - rare)
- Aplasia (blind ending bronchus, no lung or vessel)
- Hypoplasia (bronchus and rudimentary lung are present, but all elements are reduced in size and number - common)
What causes hypoplasia of the lung?
- Usually secondary
- Due to lack of space (hernia, ogliohydramnios, lymphatic or cardiac mass)
- Lack of growth (congenital)
What is cystic pulmonary airway malformation?
- Defect in pulmonary mesenchyma, abnormal differentiation 5-7th week
- Normal blood supply
- Type 2 involves multiple small cysts
What is congenital lobar emphysema?
- Progressive lobar overexpansion
- Caused by weak cartilage, extrinsic compression, one way valve effect.
- Alveoli can expand
- Associated with CHD
Discuss the prevalence of congenital lobar emphysema.
- More common in the Left upper lobe, then right middle and then right upper lobe
- Affects males more than females
What is intralobar sequestration?
- Abnormal segment share
- No communication to tracheobronchial tree
- Lower lobe predominance
- Due to chronic bronchial obstruction
