17. Lung development Flashcards
Describe the timeline of lung development
Embryonic phase (0-7 weeks): Lung buds and Main bronchi
Pseudoglandular (5-17 weeks): Conducting airways, Bronchi and bronchioli
Canalicular (16-27 weeks): Respiratory airways and Blood gas barrier
Saccular/Alveolar (28-40 weeks): Alveoli appear
How does blood vessel development in the airways occur?
In parallel with airway development
Lots of interaction between blood vessels and airways in lung development, very dependent on each other
Describe the timeline of blood vessel development in the lung
Vasculogenesis
Branching morphogenesis
Blood gas barrier
Alveo- and angiogenesis
Describe organogenesis in the lungs
Asymmetric
Right lung: 3 lobes
Left lung: 2 lobes
Describe Pseudoglandular phase (5-17 weeks)
Branching morphogenesis of airways into mesenchyme
Pre-acinar airways all present by 17 weeks
Beginning of development of cartilage, gland and smooth muscle tissue
What factors drive branching morphogenesis?
Lung buds: consistent appearance during airway formation (5-17 weeks in man)
Epithelial cells at tips of 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
Describe the inductive (stimulatory) factors in lung development
FGF: branching morphogenesis, subtypes found in epithelium and mesenchyme
EGF: epithelial proliferation and differentiation
Describe the inhibitory factors in lung development
TGF-Beta: matrix synthesis, surfactant production, inhibits proliferation of epithelium and blood vessels
Retinoic acid: inhibits branching
Describe the effects of Vascular EGF released from the tip of the lung bud on endothelial cells
Endothelial cells differentiate and coalesce to form capillaries
Airways act as a structural template:
create a physical stimulus by growing into mesenchyme, stimulates production of growth factors required for neighbouring cells to differentiate
What is branching morphogenesis matched by?
Vasculogenesis
Describe the canalicular stage (16-27 weeks)
Airspaces at the periphery enlarge
Thinning of epithelium around underlying capillaries allows gas exchange (prep. blood gas barrier)
Epithelial differentiation into Type I (thin out) and Type II cells (produce surfactant)
Surfactant 1st detectable at 24-25 weeks: reduces surface tension, allows airspaces to stay open even when airways collapse down
Describe the mechanism of formation of alveolar walls
Saccule wall, epithelium on both sides with double capillary network. Little bumps in which Myofibroblast produces elastin fibres at intervals along wall .
Secondary septa develop from wall, led by elastin produced by myofibroblast. Capillary lines both sides with matrix between.
Alveolus
Capillaries have coalesced to form 1 sheet alveolar wall, thinner and longer with less matrix. Muscle and elastin still at tip
Describe the Saccular/Alveolar stage (28 – 40 weeks)
Alveoli appear
Multiply up to 9-12 years of age
~ 1/2 adult number by term (100-150 million)
Describe the lung at birth in man
Volume small and related to body weight
All airways present and differentiated
Same blood gas barrier as in adult (smaller and less developed, but has same function)
Have 33-50% alveoli that they will have when they’re fully grown (still allow normal gas exchange)
Most arteries and veins present
3 mechanisms to increase flow after birth
Take 1st breath
Change in blood pressure
Growth of alveoli through childhood
What happens when a baby takes its 1st breath?
Expansion of alveoli dilates arteries: direct physical effect
Expansion stimulates release of vasodilator agents (NO, PGI2)
Inhibition of vasoconstrictors present during foetal life (ET)
Direct effect of oxygen on smooth muscle cells
How does blood pressure change at birth?
Decrease in pulmonary vascular resistance
10 fold rise in pulmonary blood flow
Arterial lumen increases and wall thins rapidly
Once thinning has occurred, arteries grow and maintain a relatively thin wall
We want a: low pressure, low resistance pulmonary vascular system
Growth of alveoli through childhood
Alveoli increase in number up to adolescence (Adult 300-600 million)
Alveoli increase in size and complexity to increase SA until body growth complete after adolescence
Arteries, veins and capillaries increase alongside the alveoli
Describe the epithelium of the airways
Columnar epithelium
Goblet cells produce mucins (mucous secreted onto surface)
Ciliated surface: wafts mucous (primary defence)
Primary ciliary dyskinesia
Impact on ciliary function e.g. Outer/ Inner dynein arm defect
No muco-ciliary clearance, mucous accumulates
Chronic suctive lung disease
Describe the structure of cilia
Highly conserved structure
9 + 2 formation
Microtubule doublet pairs
All have hooks (Dynein arms) which affect sliding motion of 1 microtubular pair against the other
Congenital bronchial cartilage defects:
What causes generalised malacia (floppiness)?
Slow development
Laryngotracheomalcia
Congenital bronchial cartilage defects:
What causes localised malacia (floppiness)?
Malacic segment often occur due to some other developmental issue e.g. abnormal blood vessels around heart
Causes external compression of airways, so cartilage rings don’t develop normally
What can go wrong with cartilage development?
Cartilage may form complete ring instead of horseshoe (narrowing of airway)
Laryngomalacia: omega shaped epiglottis, can collapse in on inhalation= airway obstruction
