lun development

Question 1

timeline of lung development

Answer 1

Embryonic phase: 0-7 weeks - lung buds and main bronchi form
Pseudoglandular phase: 5-17 weeks - conducting airways and bronchi/bronchioli form
Canalicular phase: 16-27 weeks - respiratory airways and blood gas barrier forms
Saccular/Alveolar phase: 28-40 weeks - alveoli phase
Postnatal/Adolescence phase: alveoli multiply and enlarge in size with chest cavity

Question 2

what is vasculogenesis

Answer 2

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

Question 3

what is embryogenesis

Answer 3

Embryogenesis: asymmetric branching occurs to produce 3 lobes on the right and 2 on the left

Question 4

what happens in the pseudoglandular phase?

Answer 4

Pseudoglandular Phase: branching morphogenesis of airways to the mesenchyme, with pre-acinar airways all present by 17 weeks; development of cartilage, glands and smooth muscle continues to canalicular phase

Question 5

factors driving branching morphogenesis

Answer 5

Factors driving morphogenesis: lung buds drive development - at tip are progenitor multipotent cells that differentiate to range of lung cells based on chemical environment, stretching to mesenchyme due to growth factors and inhibitors; communication with and physical growth into the mesenchyme leads to production of growth factors to cause morphogenesis - creating a balance

Question 6

what are the inductive and inhibitory growth factors in lung development?

Answer 6

Inductive factors:
FGF: causes branching morphogenesis
EGF: epithelial proliferation and differentiation

Inhibitory factors:
TGFbeta: matrix synthesis, surfactant production and inhibition of proliferation of epithelium/blood vessels
Retinoic acid: inhibits branching

complex signalling between GF’s, cytokines, receptors in the regulation of lung growth and differentiation

Question 7

what happens in endothelial differentiation

Answer 7

Endothelial differentiation: endothelial cells differentiate in mesenchyme due to production of vascular EGF production at the tip, coalescing to form capillaries in vasculogenesis, with airways acting as a structural template

branching morphogenesis is matched by vasculogenesis

Question 8

what happens in canalicular stage?

Answer 8

Canicular Phase: peripheral airspaces enlarge, with thinning of epithelium by underlying capillaries to allow gas exchange, but forming blood gas barrier required in post-natal life; epithelium differentiates to type I (thin)/II (surfactant - surface tension and allows re-expansion) cells and surfactant detectable at 24-25 weeks - babies become viable at 24 weeks gestation due to surfactant

Question 9

mechanism for formation of alveolar walls

Answer 9

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; myofibroblasts produce elastin that cause expansion of saccule wall into airspace
Secondary septa: develop from wall using elastin produced by myofibroblasts
Alveolar walls: capillaries coalesce to form one sheet alveolar wall, thinner and longer with less matrix, and muscle/elastin at tip

Question 10

saccular/alveolar stage occur when?

Answer 10

28-40 weeks
alveoli appear from 29/40 and multiply up to 9-12 years of age
one third to one half adult number by term

Question 11

how are the lungs at birth?

Answer 11

small volume, related to body weight; all airways present and differentiated, with most arteries and veins but only 33-50% of alveoli present

Question 12

possible mechanisms to increase flow after birth

Answer 12

Mechanisms to increase flow after birth:
Expansion of alveoli dilate arteries to increase blood flow
Expansion stimulates release of vasodilators such as NO/PGI2
Vasoconstrictors present during foetal life - if they are not inhibited then will get pulmonary hypertension
Direct effect of oxygen on smooth muscle cells could promote flow increases

Question 13

changes at birth in blood vessels

Answer 13

Decrease in pulmonary vascular resistance
10 fold increase in pulmonary blood flow
Arterial lumen increases and wall thins
Change in cell shape and cytoskeletal organisation to allow thinning (arteries grow and maintain thin walls)

LOW PRESSURE, LOW RESISTANCE PULMONARY VASCULAR SYSTEM

Question 14

childhood and adolescence growth of alveoli

Answer 14

alveoli increase in number until puberty/adulthood, with surface area increasing until body growth complete after adolescence; arteries, veins and capillaries increase alongside alveoli

Question 15

congenital bronchial cartilage defects

Answer 15

normally incomplete rings with irregular plates, but can be malacic (floppy) in generalised or localised (occur due to other developmental issue) fashion - always check CVS status

Question 16

what is laryngomalacia:

Answer 16

omega shaped epiglottis with folds that collapse on inspiration - severe airway obstruction

Question 17

lung growth anomalies

Answer 17

Agenesis: complete absence of lung and vessel - rare and associated with other conditions
Aplasia: blind ending bronchus with no lung or vessel
Hypolasia: bronchus and rudimentary lung present but all elements reduced in size and number; relatively common and 2/2 other (physical) factors such as lack of space intra/extrathoracically - can be corrected with in utero surgery

Question 18

cystic pulmonary airway malformation

Answer 18

1:8,000-1:35,000 mostly diagnosed on antenatal ultrasound; lethal don’t survive but usually seen well; normal blood supply with defect in pulmonary mesenchyma causing abnormal differentiation in early weeks

Question 19

Congenital lobar emphysema:

Answer 19

Congenital lobar emphysema: progressive lobar overexpansion, expanding over midline and squashing other lobes due to weak cartilage or one way valve effects - association with CHD

Question 20

Intralobal sequestration:

Answer 20

Intralobal sequestration: lower lobes usually affected and have aberrant blood supply that do not ventilate - no communication to tracheobronchial tree