Resp 15 - Lung development Flashcards
When does the tracheal bud develop from the foregut?
4-5 weeks
By what point is bronchial branching complete?
16 weeks
Describe the steps in the timeline of development of lungs.
Embryonic phase - 0-7 weeks; lung buds, main bronchi
Pseudoglandular - 5-17 weeks; conducting airways, bronchi & btonchioli
Canalicular - 16-27 weeks; respiratory airways, blood gas barrier
Saccular/Alveolar - 28-40 weeks; alveoli appear
How does branching morphogenesis happen?
Happens in mesenchymal tissue. Lung bud pushes into mesenchyme to form airways which divide.
When is pseudoglandular phase? What happens?
5-17 weeks
Branching morphogenesis of airways into mesenchyme.
Pre-acinar airways all present by 17 weeks.
Development of cartilage, gland and smooth muscle
Which factors drive branching morphogenesis?
There are inductive (ex FGF, EGF) and inhibitory (TGFbeta, retinoic acid) growth factors.
Complex signaling between GF, cytokines, receptors to control growth.
Epithelial cells at tip of bud are highly proliferative multipotent progenitor cells
How are capillaries formed during lung development?
Endothelial cells differentiate in the mesenchyme surrounding the lung bud. They collapse to form capillaries - process called vasculogenesis.
VEGF produced by epithelial cells stimulates endothelial differentiation.
Which phase happens during 16-27 weeks? What happens?
Canalicular stage
Start to see structure of airways at the periphery.
Thinning of epithelium by underlying capillaries allowing gas exchange - blood-gas barrier, epithelial differentiation into types I and II.
Surfactant 24-25 weeks (baby viable 24 weeks)
Describe the mechanism of formation of alveolar walls.
- saccule wall, epithelium on both sides with double capillary
- Secondary septa develop from wall led by elastin produced by myofibroblasts. Capillary lines both sides with matrix between.
- Alveolar wall formation - one sheet, capillaries coalesced.
What happens after Cannalicular stage?
Saccular/Alveolar stage- 28-40 weeks.
Alveoli appear.
1/3 to 1/2 of adult number at term.
How does an infant go from placental circulation to normal lung circulation?
- Expansion of alveoli dilates arteries; direct physical effect.
- Expansion releases vasodilators (NO, PGI2)
- Inhibition of vasoconstriction present during foetal life (ET)
- Direct effect of oxygen on SMC.
- -> decrease in pulmonary vascular resistance
- > low pressure, low resistance
What type of epithelium lines the airways?
Single layer of columnar epithelium
What is another name for primary ciliary dyskinesia?
Kartagener’s syndrome
What happens in primary ciliary dyskinesia?
Mutation of cilia. Causes inadequate mucus clearance because no hooks to hold onto mucus.
What is the only complete cartilage ring around the trachea?
Circoid cartilage
What are the types of lung growth abnormalities?
Agenesis (complete absence)
Aplasia - blind ending bronhcus, no vessel
Hypoplasia - all present but reduced in size
By what is caused hypoplasia? Give examples
- Lack of space; intrathoracic or extrathoracic. Eg. hernia, chest wall pathology, lymphatic/cardiac mass.
- Lack of growth
Eg. Congenital Thoracic Malformation CTM
What causes agenesis?
Abnormal flow in 4th week. Commonly associated with other pathology. Rare.
What is Cystic Pulmonary Airway Malformation CPAM (aka CCAM)?
Defect in pulmonary mesenchyma, abnormal differentiation 5-7th week.
Normal blood supply.
Type 2 CCAM - multiple small cysts
Associated with renal agenesis, CV defects, diaphragm hernia. Overgrowth of bronchiolar epithelium.
What is Congenital Lobar Emphysema aka Congenital Hyperlucent Lobe (CLHL)?
Progressive lobar expansion
Underlying cause: weak cartilage, compression, alveoli expand..
On scan looks like emphysema in smokers - lots of air because bronchi blocked.
Describe intralobar sequestration.
Growth of a part of lung that is not connected to the rest, ie. bronchi.
Abnormal blood supply which can be quite significant – need to block vessel by cardiologist, otherwise shunting can cause heart failure.
