16 Lung Development Flashcards
Q: What is the function of the lung? what else is needed? What can a better understanding in lung development lead to?
A: Function of lung is to produce a large gas exchange area [100m2] in a relatively small volume
-good pulmonary vasculature
may help treat and repair damaged lungs in later life (and diagnostics)
Q: What can affect lung growth? (3) What effect can abnormalities have?
What determines normal lung development?
A: Conditions of conception, in utero and in infancy affect lung growth and abnormalities may have life long impact
Crucial interaction between the airways and pulmonary vessels throughout development (send chemical messengers to and from structures)
Q: Timeline for lung development. Explain 5 stages- time and what grows.
What’s happening along side this growth?
A: 4 stages in utero
Embryonic phase – 0-7 weeks
lung buds (pushing out into mesenchymal tissue)
main bronchi (trachea branching into them)
Pseudoglandular – 5-17 weeks
conducting airways
bronchi & bronchioli (ongoing branching/ bifurcations)
Canalicular – 16-27 weeks
respiratory airways (laying down of)
blood gas barrier (basic components start developing)
Saccular/Alveolar -28-40 weeks
Alveoli appear
stage where infants become viable
Postnatal – adolescence
Alveoli multiply and enlarge in size with chest cavity (Alveoli appear before birth and continue to grow in early childhood)
blood vessel development
Q: 3 stages of blood vessel development (of lungs). Include what stage of lung development they coincide with.
A: Vasculogenesis // Branching morphogenesis
- occur along the skeleton that airway creates
- during embryonic and pseudoglandular phase (1 and 2)
Blood gas barrier
- during canalicular phase (phase 3)
Alveologenesis (formation of new alveoli) and angiogenesis (new blood vessels form from old ones)
- during saccular/adolescence phase (phase 4)
Q: Branching during embryogenesis. (3)
A: determines lobes-> can see branching buds growing into mesenchymal tissue
begins as asymmetric
can see by 56 days 3 lobes of right and 2 of left
Q: When does the pseudoglandular phase occur? Main process occurring? What is present by the end of it? What continues to develop? (3) in what phase?
A: 2nd phase, 5-17 weeks
Branching morphogenesis of airways into mesenchyme
Pre-acinar airways (conducting airways, not part of gas exchange) all present by 17 weeks
Development of cartilage, gland and smooth muscle tissue – continues into canalicular phase
Q: What determines branching morphogenesis? 3 examples. Describe the involvement of 2 cells.
What pattern does branching occur in humans?
A: Communication between epithelial cells in distal branching lung buds and surrounding mesenchyme (Epithelial-mesenchymal interaction) eg growth factors, cytokines and receptors
- Epithelial cells at tips of buds are highly proliferative multipotent progenitor cells
- Cells behind the tip divide and differentiate into the various cell types
bifurcation pattern
Q: What factors are involved in early lung bud formation? (2) Later?
A: Genetic and Transcription factors [TTF-1]
Later a variety of growth factors are important
Q: Name 4 growth factors in lung development. Include role. Balance?
A: Inductive/stimulating
FGF- branching morphogenesis, subtypes found in epithelium and mesenchyme
EGF - epithelial proliferation and differentiation
Inhibitory
TGFb - matrix synthesis, surfactant production, inhibits proliferation of epithelium and blood vessels
Retinoic acid - inhibits branching
without inhib you get overgrowth/malignancies
Q: Describe the process of endothelial differentiation. Where? (2) what makes them visible? What can happen to some? process? What stimulates endothelial differentiation?
End result?
A: (blood vessels)
CD31 (brown) demonstrates endothelial cells -> see them growing around lung bud-> along skeleton created by branching airways (act as structural template)
These differentiate in the mesenchyme around the lung bud
They coalesce to form capillaries – a process known as vasculogenesis
VEGF produced by epithelial cells (at tip of lung bud)
get pulmonary vasculature-> where blood vessels grow around alveoli = capillary beds -> where most gas exchange occurs
Q: When does the canalicular phase occur? What occurs? (4)
A: 16-27 weeks
- The airspaces at the periphery enlarge
- Thinning of epithelium by underlying capillaries allows gas exchange (Blood gas barrier)
- Epithelial differentiation into Type I and II cells (I produces surfactant)
- Surfactant first detectable at 24-25 wks (TGFb)
Q: Role of surfactant?
A: prevent airways sticking together with you breathe out
Q: Describe the 3 stage formation of the alveolar walls. Draw associated image. When does this occur? How does the interstitium change?
A: 1. Saccule wall, epithelium on both sides with double capillary network. Myofibroblast (produces elastin) and elastin fibres at intervals along wall (interstitium quite thick)
- Secondary septa develop from wall led by elastin produced by myofibroblast. Capillary lines both sides with matrix between
- Capillaries have coalesced to form one sheet alveolar wall, thinner and longer with less matrix. Muscle and elastin still at tip (thinned interstitium)
last 10 weeks (saccular/alveolar phase)
Q: How does the number of alveoli change as we grow? Diagram.
A: REFER
at 40 weeks when we’re born= 150 million -> 1/3 of the amount we are to have in adulthood
continues until late adolescence or early adulthood
Q: Infants born at term. Describe the lungs. What is present? (4)
A: small lung volume and related to body weight
- All airways present and differentiated (cartilage, glands, muscle, nerves)
- 33-50% alveoli allow normal gas exchange
- Blood gas barrier as in adult
- Most arteries and veins (pulmonary vascular system) present
