Lung developmentf

Question 1

the lung at birth

Answer 1

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

Question 2

mechanisms to increase flow after birth

Answer 2

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

Question 3

changes in bv at birth

Answer 3

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

Question 4

changes in alveoli in childhood

Answer 4

number increase to 9-12yrs
increase in size and complexity t0 increase SA x20
bv increase alongside alveoli - cap vol x35

Question 5

effect of post natal development

Answer 5

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

Question 6

exponential growth of alveoli

Answer 6

new born 150million alveoli

adult 300-600million

Question 7

blood vessel development

Answer 7

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

Question 8

morphogenesis of the lung

Answer 8

asymmetric

Question 9

pseudoglandular phase

Answer 9

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

Question 10

factors driving branch morphogenesis

Answer 10

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

Question 11

GF in lung development

Answer 11

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

Question 12

endothelial diff in pseudoglandular phas

Answer 12

diff in mesenchyme around bud
endo cells coalesce to form capillaries - vasculogeneis
act as structural template
VEGF produced by epi cells stimulates endo diff

Question 13

Canalicular stage

Answer 13

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

Question 14

mechanism of formation of alveolar walls

Answer 14

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

Question 15

blood gas barrier development

Answer 15

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

Question 16

airway epi

Answer 16

columnar
goblet produce mucin
ciliated, motile - primary defence mech - clear debris by mucociliary escalator
there are many inherited conditions causing resp ciliopathy

Question 17

inherited ciliary mutations

Answer 17

autosomal mutation
45 known inherited
primary ciliary dyskinesia

Question 18

cilia

Answer 18

9+2 arrangement
microtubule doublet pairs
hook - ATPase unit - slide 1 pair over the other

Question 19

primary ciliary dyskinesia

Answer 19

chronic suppurative lung disease - progressive
get bronchiectasis early
resp failure
dynein arm gone - lose primary defence mech

Question 20

congenital bronchial cartilage defects

Answer 20

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

Question 21

laryngomalacia

Answer 21

omega shaped epiglottis
aryepiglottic folds not sat nicely
breathe in - collapse and occlude vocal cords
in growth fixes itself - tracheostomy until then

Question 22

agenesis

Answer 22

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

Question 23

aplasia

Answer 23

blind ending bronchus - no lung or vessel

Question 24

hypoplasia

Answer 24

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

Question 25

cystic pulmonary airway malformation

Answer 25

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

Question 26

congenital lobar emphysema

Answer 26

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

Question 27

one way valve effect

Answer 27

air in but not out

Question 28

intralobar sequestration

Answer 28

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

Question 29

blood supply in intralobular sequestration

Answer 29

can go into high flow
present with cardiac failure
cardiologist embolise vessel - it shrivels and is not used

Question 30

time line of lung development

Answer 30

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

Question 31

land marks in lung development

Answer 31

6wk - lobar airway 
16wk - pre-acinar airway 
30wk - resp airway, 1st alveoli 
newborn - 1/3-1/2 adult alveoli 
3yr old - most alveoli