15 - Lung development Flashcards
What are the phases in the timeline of lung development? At how many weeks does each stage occur?
- embryonic phase: 0-7 weeks
- pseudoglandular phase: 5-16 weeks
- cannalicular phase: 16-27 weeks
- saccular/alveolar: 28-40 weeks
- postnatal/adolescence
What happens in the embryonic phase of lung development?
the lungs bud into the mesenchymal tissue
the trachea branches into the the main bronchi
What happens in the pseudoglandular phase of lung development?
- development of the conducting airways
- development of the bronchi and bronchioles
- branching morphogenesis of airways into mesenchyme
- pre-acinar airways all present by 17 weeks
- development of cartilage, gland and smooth muscle tissue – continues into canalicular phase
What happens in the canalicular phase of lung development?
- development of the conducting airways
- development of blood-gas barrier
- peripheral airspaces enlarge
- thinning of epithelium by underlying capillaries (allows age exchange)
- epithelial differentiation into Type 1 and Type 2 cells
- surfactant first detectable at 24-25 wks
What happens in the alveolar phase of lung development?
the alveoli appear
What changes in lung development occur during adolescence?
the alveoli multiply and enlarge in size with chest cavity
Describe the blood vessel development alongside the development of the lungs
the pulmonary vessels develop alongside the airways
- there is addition of newly formed endothelial tubes at the lung periphery as each airway division occurs
- as the capillaries add on at the periphery the arteries and veins get longer
- vasculogenesis and branching morphogenesis occur in the early stages of lung development
- the blood-brain barrier forms in the later stages
- alveo and angiogenesis take place very late on
What are the pre-acinar airways and when are they fully formed by?
the conducting airways that are not involved in gas exchange
present by 17 weeks
What factors drive branching morphogenesis?
- epithelial cells at tips of buds are highly proliferative multipotent progenitor cells
- the cells behind the tip divide and differentiate into the various cell types
- communication between epithelial cells in distal branching lung buds and surrounding mesenchyme
What are the control mechanisms for development?
- epithelial-mesenchymal interaction - for branching morphogenesis
- Genetic and Transcription factors [TTF-1] involved in early bud formation
- Branching development in humans follows a bifurcation pattern
- later, a variety of growth factors are important
What are the growth factors involved in lung development? (inductive and inhibitory)
inductive - FGF and EGF
inhibitory - TGFβ and retinoid acid
What is the process of endothelial differentiation?
- they differentiate in the mesenchyme around the lung bud
- vasculogenesis (they coalesce to form capillaries)
- the airwayss act as structural template
- VEGF produced by epithelial cells stimulates endothelial differentiation
End of the pseudoglandular and beginning of the canalicular phase
- all airways and blood vessels to the level of the terminal bronchiolus are present
- the appearance of the lung changes as the lung enters the canalicular stage
Give the mechanism of formation of the alveolar walls
The saccular wall has an epithelium on both sides with double capillary network. There are myofibroblasts and elastin fibres at intervals along the wall.
Secondary septa (the folds of of the alveolar sacs) develop from wall led by elastin (produced by myofibroblast). Capillary lines both sides with matrix between.
Capillaries coalesce to form one sheet alveolar wall, thinner and longer with less matrix. Muscle and elastin are still at tip
Describe the lungs at birth
Volume small and related to body weight All airways present and differentiated (cartilage, glands, muscle, nerves) 33-50% alveoli allow normal gas exchange Blood-gas barrier is fully developed Most arteries and veins present
