Lung development Flashcards
Summarise lung function and development
Function of lung is to produce a large gas exchange area [100m2] in a relatively small volume
Conditions of conception, in utero and in infancy affect lung growth and abnormalities may have life long impact
A better understanding of lung development may help treat and repair damaged lungs in later life
What is key to remember about the timeline for lung development
It’s not exact- many things can affect it
Outline the timeline of lung development
- Embryonic Phase (0à7 weeks).
a. Vasculogenesis and branching morphogenesis begins here (lung buds and main bronchi) - Pseudoglandular Phase (5à17 weeks).
a. Vasculogenesis and branching morphogenesis continues. bronchi and bronchioli- conducting airways - Canalicular Phase (16à27 weeks).
a. Respiratory tissue begins to grow here. (respiratory airways)
b. Blood gas barrier supply forms. - Saccular/Alveolar Phase (28à40 weeks).
a. Alveolar and angiogenesis occurs. - Postnatal (adolescence).
What do the canalicular and sacular phases allow for
gas exchange
Outline the blood vessel development in the lungs
vasculogenesis and branching morphology takes place in the embryonic and pseudogladnular phase
Blood gas barrier forms in the canalicular phase
alveo and angiogenesis in the sacular phase
What is important to remember about lung and blood vessel development
They are dependent on each other
Vasculogenesis: occurs in parallel with lung development - form around framework provided by budding airways; not until canalicular phase does blood brain barrier form - infant only viable after canalicular phase
Physical and chemical factors involved
When does the majority of this development take place
The majority of this complex airway and circulatory system grows during early fetal life
Alveoli appear before birth and continue to grow in early childhood
Crucial interaction between the airways and pulmonary vessels throughout development
bloog gas barrier complete in canalicular phase- this is when you become viable
Is lung development complete at the point of birth
No- alveoli continue to grow and develop post-natally, but you can still perform gas exchange
Describe the embryonic phase
Trachea splits into bronchial buds (28 days)
Bronchial buds split into secondary bronchi (35 days)
42 days- the branching becomes more extensive and lungs grow- forming the lobes of the lungs
56 days- lungs grow- more extensive branching
See Diagram!
What is key to remember about the embryogenesis of the lungs
It is asymmetric
Right lung develops 3 lobes
Left 2
§ Individual lobes can be affected and shown up on x-rays so for example, a single lobe may display oedema.
Right more vertical- foreign bodies more likely to lodge in right inferior or middle lobe
Summarise what happens in the pseudoglandular phase
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 does the lung bud contain
Stem cells
Which can differentiate into different cells depending on the chemical and physical environment
growth factors- will cause them to expand and grow into the mesenchyme
Growth stimulated by growth of mesenchyme for balanced growth (prevents hyperplasia)
Can get overgrowth in poorly modelled lungs
Describe the factors that affect branching morphogenesis
Lung buds - consistent appearance during airway formation (5-17 wks 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
Complex signalling between GF’s, cytokines, receptors in the regulation of lung growth and differentiation
Describe the inductive factors in branching morphogenesis
FGF- branching morphogenesis, subtypes found in epithelium and mesenchyme
EGF - epithelial proliferation and differentiation
Describe the inhibitory factors in branching morphogenesis
TGFb - matrix synthesis, surfactant production, inhibits proliferation of epithelium and blood vessels
Retinoic acid - inhibits branching
What pattern does morphogenesis follow in humans
A bifurcation pattern
Describe endothelial differentiation in the pseudoglandular phase
CD31 (brown) demonstrates endothelial cells
These differentiate in the mesenchyme around the lung bud
They coalesce to form capillaries – a process known as vasculogenesis
Airways act as structural template
VEGF produced by epithelial cells stimulates endothelial differentiation
The brown cells form a lattice around the lung bud
Learning point: Branching morphogenesis is matched by vasculogenesis
Summarise the canalicular phase
The airspaces at the periphery enlarge
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 wks
Babies become viable at 24 weeks.
Describe the difference in the histology in the type 1 and type 2 pnuemocytes
1- thin right out
2- round- produce surfactant
Describe the mechanisms behind alveolar wall formation
airways enlarge and only one layer of capillaries present around each air sac
Saccule wall, epithelium on both sides with double capillary network. Myofibroblast and elastin fibres at intervals along wall (elastin allows expansion)
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- this is the alveolus (forms at around 38th week)
When do alveoli appear
Alveoli appear from 29/40 and multiply up to 9-12 years of age
One third to one half adult number by term (100-150 million)
What happens at each airway division
Sustained 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
What happens to the alveolar number in infants post-natally
alveolar number increases in infants as post-conceptional age increases
from about 150 x 10^6
to about 400 x 10^6 by 80 weeks post-conception
Describe the lungs at birth in man
Volume small and related to body weight All airways present and differentiated (cartilage, glands, muscle, nerves) Blood gas barrier as in adult 33-50% alveoli allow normal gas exchange Most arteries and veins present
