Lung development Flashcards
How many phases are there in lung development, and what are they and how long does it take?
1. Embryonic phase (0-7 weeks) Vasculogenesis and branching morphogenesis begins here. 2. Pseudoglandular phase (5- 17 weeks). Vasculogenesis and branching morphogenesis continues 3. Canalicular phase (16-27 weeks) Respiratory tissue begins to grow here. Blood gas barrier supply forms. 4.Saccular/ alveolar phase (28-40 weeks) Alveolar and angiogenesis occurs. 5. Postnatal (adolescence)
When does the tracheal bud develop from the foregut?
4-5 weeks
By what point is bronchial branching complete?
16 weeks
what is the timeline of lung development?
- majority of the network develops during early foetal life
- alveoli appear before birth and continue to grow in early childhood
- vasculogenesis closely matches the airway generation throughout development.
what is scimitar syndrome and what is it characterised by?
-Anomalous pulmonary venous drainage of the right lung to the IVC, usually close to the junction of the right atrium.
There is associated right lung and right pulmonary artery hypoplasia.
o Essentially a small right lung with hypoventilation.
- Characterised by Dextrocardia (heart is pulled to the right instead of left).
- Anomalous systemic arterial supply.
- To the right of the IVC, you can see a scimitar shaped vessel, hence name.
what happens during embryogenesis?
- Left lung develops into 2 lungs
- right lung develops into 3
what is malacic?
Abnormal softening of organs or tissues
what happens during the pseudo-glandular phase?
Characterised by branching morphogenesis of airways into mesenchyme.
which lobe is where objects get stuck?
Middle lobe of right lung is most often affected by aspirations as objects fall into it.
What factors drive branching morphogenesis?
Lung buds- consistent appearance during airway formation.(5-17 weeks in man).
o Epithelial cells at the tips of each bud are highly proliferative and can differentiate as needed.
o Genetic and transcription factors (TFF-1) are involved in early bud development.
- Epithelial-mesenchymal interaction essential for branching morphogenesis.
- Branching in humans follows a bifurcation pattern.
What are the growth factors for lung development- inductive?
FGF- for branching morphogenesis
EGF- epithelial proliferation and differentiation
What are the growth factors for development- inhibitory
TGF-beta: matrix synthesis, surfactant production, inhibits proliferation of epithelium and angiogenesis.
Retinoic acid: inhibits branching
what is primary ciliary dyskinesia
A movement disorder due to a loss ciliary proteins in the axon.
The dyein arms required to lose cilia are lost
what week is a circulation present?
A circulation is present by 5 weeks gestation
What are some congenital thoracic malformation?
- CPAM/CCAM- congenital pulmonary airway malformation. Known as Congenital cystic adenomatoid malformation(CCAM)
Characterised by a defect in pulmonary mesenchyma with abnormal differentiation in the 5th-7th week.
A normal blood supply is present but it can be associated with sequestration.
Type 2 CPAM/CCAM is characterised by mulitple small cysts which pool in the lung tissue and is caused by hyperplasia of epithelium separated by underdeveloped alveolar tissue. Can be associated with renal agenesis, CVD defects and diaphragmatic hernias.
Congenital Lobar Emphysema/ Congenital Large Hyperlucent Lobe (CLHL): Progressive lobar overexpansion. Due to weak cartilage, extrinsic compression, one-way valve effect or alveoli expansion. CHD association. Affects more males than females.
- Intra-lobar Sequestration – Makes up 75% of pulmonary sequestrations.
* Sequestration – loss of blood or its fluid content into spaces within the body.
* Characterised by abnormal segment share of visceral pleura covering of the normal lung – the loss of connection of the lobes with the bronchial tree and pulmonary veins.
* Due to chronic bronchial obstruction and chronic post-obstructive pneumonia. - Lung Growth Abnormalities
* Agenesis – complete absence of lungs and vessels.
o VERY RARE and commonly associated with other pathology.
o Normally an associated mediastinal shift towards an opaque hemithorax.
- Aplasia – blind ending bronchus with no lung or vessels.
- Hypolasia – bronchus and rudimentary lung are all present but reduced in size and number.
o Common (relatively) and usually secondary.
o Due to a lack of space (intrathoracic/extrathoracic) or lack of growth.
what is present on endothelial cells and what do these do?
Development
- CD31 is present on endothelial cells and these differentiate into the mesenchyme surrounding the lung buds.
- The endothelial cells coalesce to form capillaries in a process known as Vasculogenesis.
- VEGF (vascular endothelial growth factor) produced by the epithelial cells stimulates the endothelial differentiation.
what is the canicular stage?
The airspaces at the peripheries enlarge.
The epithelium thins allowing efficient gas-exchange.
Epithelial cells differentiate into type 1 and 2 cells.
Surfactant first becomes detectable at 24-25 weeks.
what complications may people who are born early have?
o This group of people may be at a higher risk of airway diseases such as COPD.
o There may be scope for ‘catch-up’ growth as alveoli continue to grow after birth.
what happens to the lungs during childhood?
- Lung volume increases by 30x.
- Airways increase in length and width
- Dysanaptic growth during early period (alveoli growing more in airways).
- arteries, veins and capillaries increase.
What is a hypoplastic lung?
Interruption to bronchial branching leads to development of a small lung with little branching.
What can insults to the dividing bronchus cause?
Agenesis (early malfunction)
Local lesion
Malformation of systemic supply
Malformation in the lung leading to normal blood supply to an abnormal lung
State some factors that influence lung development.
Hox genes Thoracic cage volume Amniotic fluid volume Transcription factors Peptide growth factors Maternal nutrition e.g. Vitamin A
What is the only complete cartilage ring around the trachea?
Cricoid cartilage
How many generations of branching occur during pre-natal development of the airways?
25
What are the three stages of prenatal development of the airways?
Glandular
Canalicular
Alveolar
Describe the effects of smoking during pregnancy on airway development.
Reduces elasticity of alveoli and reduces airway diameter
This leads to a wheezy infant with increased risk of COPD in later life
What percentage of the foetal blood reaches the lungs?
10%
State two differences between foetal blood and adult blood.
Foetal pH = 7.2 (normal = 7.4)
Foetal pO2 = 3.4 kPa (normal = 10 kPa)
What changes occur at birth?
Changes in prostaglandins causes the closing of the ductus arteriosus
Increase in left atrial pressure closes the foramen ovale
Systemic pressure increases and becomes greater than pulmonary pressure
There is massive CNS stimulation due to a change in environment
Placental circulation is cut
Lung aeration causes fall in pulmonary arterial pressure (as lungs stretch)
Increase in PO2 + decrease in PCO2
–Arterial lumens’ diameter increase and walls thin rapidly– wall is then maintained.
What happens in the first day post birth?
Pulmonary vasodilation increases 5 fold thus increasing pulmonary blood flow
Aeration of the lungs and the lung volume increases to optimum
Within the first 2 hours resistance falls
Lung compliance rise takes around 24 hours - lymphatics is relied upon to remove the fluid from the lungs
PO2 increases, PCO2 decreases –> pH increases
How can the foetus cope with the low PO2?
Foetal haemoglobin has a higher affinity for oxygen than adult haemoglobin
Describe the two failures of breathing that could happen during birth?
Primary apnoea - attempted breathing occurs at birth. With umbilical strangulation, the gasp fails.
Terminal apnoea - second attempt at breathing (with failure of successful ventilation) results in a DECREASED BLOOD PRESSURE. Heart rate is relatively maintained.
What scale is used to determine the severity of the apnoea and the need for resuscitation?
Apgar scale
What produces surfactant in a foetus?
Lamellar Bodies in Type II Pneumocytes
What does surfactant do?
Creates a force resulting in the distension and maintenance of distension of the airways at lower pressures so the airways remain open
When is surfactant produced during pregnancy?
Late 2nd trimester, early 3rd trimester
What can a lack of surfactant cause and what is this called?
Increased risk of alveolar collapse –> hypoventilation + hypoxic acidosis –> pulmonary vasoconstriction + right to left shunting
Idiopathic respiratory distress syndrome
What is another name for primary ciliary dyskinesia?
Kartagener’s syndrome
How does elasticity and compliance change with age?
Elasticity and compliance decrease
