What are the four main stages of intrauterine lung development?
- Embryonic phase (0-7 weeks)
- Pseudoglandular phase (5-17 weeks)
- Canalicular phase (16-27 weeks)
- Saccular/alveolar phase (28-40 weeks)
post natal to adulthood the alveoli multiply
When does life become viable?
once alveoli are developed and surfactant is produced (24 weeks)
How do vasculogenesis and branching morphogenesis occur?
Vasculogenesis and branching morphogenesis occur along the skeleton created by the airways. Later on the blood gas barrier forms and then alveoli and angiogenesis.
Are the lungs and branching symmetric?
No, the lungs are asymmetric and so branching is also asymmetric
What happens during the embryonic phase?
The lung buds form and the main bronchi form.
What happens during the pseudoglandular phase?
Branching morphogenesis of the airways into the mesenchyme. The pre-acinar airways (non conducting) are present by 17 weeks. Development of the cartilage, glands and smooth muscle continue into the canalicular phase.
What is mesenchyme?
tissues that develop into connective and skeletal tissue
Which factors drive branching morphogenesis?
- communication between the epithelial cells and the mesenchyme
- epithelial cells in the tip which are multipotent and proliferative so differentiate into different cell types
- lung buds
Which growth factors are involved in lung development?
Inductive:
1) FGF - brnaching morphogenesis
2) EGF - epithelial proliferation and differentiation
Inhibitory:
1) TGF beta - matrix synthesis, surfactant production, inhibits epithelium and blood vessel proliferation
2) Retinoic acid - inhibits branching
There is complex signalling between the GFs, cytokines and receptors.
What is VEFG?
It is a stimulating GF made by cells at the tip of the lung bud to stimulate endothelial cells to proliferate an form the capillary network
What happens during the canalicular phase?
- The airspaces at the periphery enlarge
- thinning of the epithelium underlying capillaries
- epithelial differentiation into type 1 and 2 cells
- surfactant detectable at 24 weeks
- blood gas barrier forms
At term how much of your adult alveoli should you have and when is the full number achieved?
At term you should have a third of your alveoli and this number increases until adolescence/adulthood.
How does the lung at birth compare to the lung in an adult?
- the volume is small relative to body mass
- all airways present and differentiated
- blood gas barrier same
- 33-50% alveoli but normal gas ecchange
- most arteries and vein present
What are the mechanisms allowing the baby to go from placental circulation to air?
- Expansion of the alveoli during breathing dilates the arteries and reduced the blood pressure in the system so that blood can flow (reduced resistance)
- expansion stimulates the release of vasodilators such as NO
- inhibition of vasoconstrictors present during fetal life
- effect of oxygen on smooth muscle cells causing them to relax and this aids vasodilation
What are the changes at birth in blood vessels?
- decrease in pulmonary vasculature resistance
- rise in pulmonary blood flow
- arterial lumen increases and wall thins
- change in cell shape and cytoskeletal arrangement
- once thinning occurs the arteries grow and maintain a thin wall
(low pressure and low resistance in the pulmonary vasculature)
How do alveoli change into adulthood?
- number increases
- size increases
- complexity increases
- arteries, vein and capillaries increase alongside
When are the first alveoli seen?
Around 30 weeks
What happens to newborns with primary ciliary dyskinesia?
They cannot clear the amniotic fluid or mucus so they stay in ICU
What are some problems that can occur with bronchial cartilage?
- incomplete rings posteriorly
- irregular plates
- calcify with age
- can be malcic (softened): localised means there is a malacic segment or generalised such as larygotracheomalacia
What is a problem that could occur with the tracheal cartilage?
You could have a complete trachial ring which would require a tracheostomy.
What is laryngomalacia?
The softening of the cartilage - the epiglottis becomes omega shaped and when the patient breathes, the epiglottis blocks the airways.
What are some of the main lung growth abnormalities?
- agenesis (complete absence of lung and vessels)
- aplasia (blind ending bronchus so no lung or vessel)
- hypoplasia (bronchus and lung are present but they are reduced in size
Agenesis
It is rare and occurs early in embryogenesis
- commonly associated with another pathology e.g. congenital heart disease
- mediastinal shift of the heart to the unoccupied side
Hypoplasia
- common compared to others
- usually secondary to a lack of space (intra or extrathoracic) e.g. caused by diaphragm pushing into the chest. Or by oligohydramnios (reduced amniotic fluid so not enough space to grow). Another cause is lymphatic/cardiac mass or a small ribcage (Jeune syndrome)
- can also be caused by a lack of growth e.g. congenital thoracic malformation
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Respiratory system anatomy36
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Ventilation75
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Gas Exchange51
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Lung cell biology32
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Structure and function of airways40
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Breathlessness and control of breathing (awake)41
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Respiratory pathology - Lung cancer31
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Sensory aspects of respiratory pathology43
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Gas exchange unit16
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Lung infections21
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Control of breathing during sleep24
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Patient examination10
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Hypoxia33
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Allergic airways disease31
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Thoracic ultrasound26
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Lung infection - sofia27
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Acid - Base regulation24
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Exercise physiology24
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Lung development30
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pulmonary circulation25
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Heart Failure28
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Lung mechanics34
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Tutorial9
