Lung developmentf Flashcards
the lung at birth
vol small
related to height
airways present and diff - cartilage, glands, muscle and nerves
blood gas barrier present - less developed and smaller
30% alveoli = GE
most artery and veins present
mechanisms to increase flow after birth
expansion of alveoli dilates arteries - physical effect, need big breath
expansion stim release of vasodilator agents NO and PGI1
inhib of vasoconstrictors in foetus - ET - otherwise have pul hypertension
direct effect of O2 on sm
changes in bv at birth
decrease in vascular resistance 10fold rise in flow lumer increases in arteries, wall thins change in cell shape and cytoskeleton organisation - not loss of cells arteries grow and keep thin wall low pressure, low resistance
changes in alveoli in childhood
number increase to 9-12yrs
increase in size and complexity t0 increase SA x20
bv increase alongside alveoli - cap vol x35
effect of post natal development
a lot of development is postnatally
possibility of insult through exposure, infection, genetics
if lung damage to child - bigger chance of lung correcting itself - alveoli are still being layed down
exponential growth of alveoli
new born 150million alveoli
adult 300-600million
blood vessel development
interaction between bv and airway
vasculogenesis around the framework of the airway
due to physical and chemical pathways
branching morphogenesis
blood gas barrier
alveo and angiogenesis
alveoli not complete when born - but should still have functioning adult system for GE
morphogenesis of the lung
asymmetric
pseudoglandular phase
5-17 wks
branching morphogenesis of airways into mesochyme
pre-acinar airways present by 17 wks
development of cartilage, gland and sm tissue
driven by lung bud
vessels grow between mesochyme and bud
factors driving branch morphogenesis
driven by lung bud
in tip - progenitor multipotent cell - differentiate depending on env
stretch into mesochyme because of growth factors and inhibitors - cause mesochyjme to release more factors
communication between epi cells in distal branching lung buds and surrounding mesochyme
GF in lung development
FGF - branching morphogenesis, subtypes in epi and mesenchyme
EGF - epi proliferation and diff
TGFBeta - inhib matrix synth, surfactant production, proliferation of epi and bv
retinoic acid - inhibit branching
endothelial diff in pseudoglandular phas
diff in mesenchyme around bud
endo cells coalesce to form capillaries - vasculogeneis
act as structural template
VEGF produced by epi cells stimulates endo diff
Canalicular stage
16-27wks
3rd trimester
airspaces at periphery enlarge
thinning of epi by cap allow GE
blood gas barrier required in postnatal is formed
epi diff into T1 - thin and T2 - round make surfactant (reduce surface tension = no collapse)
surfactant at 24-25wks
mechanism of formation of alveolar walls
saccule wall- epi on both side, double cap network, myofibroblasts and elastin at intervals along wall
wall forms secondary septa develop from wall led by microfibroblast and elastin, cap line both sides - matrix between
then cap coalesce to form 1 sheet alveolar wall - thinner and longerm less matrix, muscle and elastin at top
blood gas barrier development
29wks - septa thick - surfactant exogenously - high pressure = tear and lung damage
8month - thin bed cap in septal - good for GE
term - don’t have to have exogenous surfactant - normal lung development and vasculogenesis
airway epi
columnar
goblet produce mucin
ciliated, motile - primary defence mech - clear debris by mucociliary escalator
there are many inherited conditions causing resp ciliopathy
inherited ciliary mutations
autosomal mutation
45 known inherited
primary ciliary dyskinesia
cilia
9+2 arrangement
microtubule doublet pairs
hook - ATPase unit - slide 1 pair over the other
primary ciliary dyskinesia
chronic suppurative lung disease - progressive
get bronchiectasis early
resp failure
dynein arm gone - lose primary defence mech
congenital bronchial cartilage defects
malacic
generalised - laryngotracheomalcia
localised - malacic segment from external compression
heart can block airways - see pulsation in trachea
have complete tracheal ring - narrow airways, need surgery - tracheostomy until done
laryngomalacia
omega shaped epiglottis
aryepiglottic folds not sat nicely
breathe in - collapse and occlude vocal cords
in growth fixes itself - tracheostomy until then
agenesis
complete absence of lung and vessel other lung permeate to other side diaphragm rise up too abnormal flow in 4th wk associated with other pathology mediastinal shift to opaque hemithorax
aplasia
blind ending bronchus - no lung or vessel
hypoplasia
bronchus and rudiamentry lung present - all elements reduced in size and numver
lack of space
relativelky common - secondary
from hernia 75-90% - bowel in chest, lung size not improved after correction of hernia
treat in foetus
chest wall pathology - dystrophy - break rib and insert titanium, on ventilator
oligohydramnios - loss of amniotic fluid
lymphatic or cardiac mass eg tumour
appear symmetrical - 1 lobe actually small
cystic pulmonary airway malformation
diagnosed with antenatal US - seen in well children
defect in pul mesenchyma
abnormal differentiation 5-7th wk
normal blood supply
badly modelled lung
associated with renal agenesis, cardiovascular defects, diaphragmatic hernia, syryngomelia
bronchiolar epithelium with overgrowth - separated by alveolar tissue that was underdeveloped
don’t know cause - not contributed to ventilation
at risk of infection - pneumonia
congenital lobar emphysema
progressive lobar overexpansion after 1st breath
caused by: weak cartilage, extrinsic compression, one way valve effect, alveoli expand - not disrupted
left upper lobe>right middle> R upper
males> females
CHD association
normally children are fine - if not can remove lobe
one way valve effect
air in but not out
intralobar sequestration
75% pul sequestrations
abnormal segment share visceral pleura covering normal lung
aberrant lung supply of blood
no communication to tracheobronchial tree - not ventilating
lower lobe prediomininance
caused by: chronic bronchial obstruction and postobstructive pneumonia
blood supply in intralobular sequestration
can go into high flow
present with cardiac failure
cardiologist embolise vessel - it shrivels and is not used
time line of lung development
embryonic phase 0-7 weeks - lung buds and main bronchi
psueudoglandular 5-17 wks - conducting airways, bronchi and bronchioles
canalicular 16-27 wks - resp airways - blood gas barrier
saccular/alveolar 28-40 wks - alveolar appear
post-natal - adolescence - alveoli multiply and enlarge until 9-12 yr old
land marks in lung development
6wk - lobar airway 16wk - pre-acinar airway 30wk - resp airway, 1st alveoli newborn - 1/3-1/2 adult alveoli 3yr old - most alveoli
