Lecture 10: Lung development and surfactant Flashcards
What are the basic embryology origins of the lung tissues?
- Lungs are primarily endodermal in origin
- Parenchyma and pleura are mesodermal
Describe the periods of the lung development;
Embryonic period (26 days to 7 weeks) Psuedoglandular period (5-17 weeks) Cannicular period (16-25 weeks) Saccular stage (24 weeks to after birth) Alveolar period (late feotal to 21 years)
Describe what happens in the embryonic period;
- Lung bud arises as VENTRAL outpouching of the foregut endoderm
- Initial 3 rounds of branching produces:
= Primordia of two lungs (primary bronchi)
= Lung lobes (Lobar bronchi)
= Bronchopulmonary segments (segmental bronchi)
Describe what happens in the psuedoglandular period:
Branching forms:
- Bronchi
- Bronchioles
- Terminal bronchioles
(Only conducting zone formed), looks like glands
Describe what happens is the cannicular period:
- Each terminal bronchiole gives rise to two or more respiratory bronchioles
- Each divides into 3-6 alveolar ducts lined by cuboidal cells.
Primitive resp. zone developed
Describe the saccular stage:
Alveolar ducts give rise to primitive alveoli
AT1 and AT2
- Surfactant starts to be produced
Describe the alveolar stage:
- Increasing n. terminal sacs
- Alveoli mature
- AT1 continue to thin
Whats the risk of the embryonic / psuedoglandular stage?
Potential for tracheal / oesophogeal separation defects
Describe the in-utero changes to the lungs;
Heart - Ductus arterosus and foramen ovale
= No O2 exchange
Describe the changes to the lungs at birth:
During birth - Compression of chest wall expells fluid from lungs +/- fluid re-absorption in lymphatics
- UC clamped, closure of DA and FO
- Inflation of lungs = Dec resistance of pulm. circuits
- Established of air:liquid interface
Why is surfactant necessary for reducing surface tension?
Surface tension needs to be lowered because:
- If the surface of the lung was plasma not surfactant, the pressure required to maintain lung volume would be 28cm water rather than 5cm water
Describe the constituents of surfactant:
95% phospholipid (polar head, non-polar tail)
5% protein
What are the surfactant proteins and structure;
SP-A (Large hydrophilic)
SP-B (small lipophilic)
SP-C (small lipophilic)
SP-D (Large hydrophilic)
What is the function of SP-A in surfactant?
- Surface tension reduction
- Host defence
- Regulation of surfactant synthesis
What is the function of SP-B in surfactant?
- Formation of tubular myelin
- Formation and stabilisation of phospholipid monolayer
What is the function of SP-C surfactant?
- Formation and stabilisation of the phospholipid monolayer
What is the function of SP-D surfactant?
- Regulation of surfactant synthesis
- Hose defence (Does not exhibit SPA’s effect on dynamic surface tension)
Describe the turnover of surfactant?
Degradation and catabolism (phospholipid turnover 3-11hrs)
- Taken up by AT2 or transported towards ciliated airways
- Degraded by extracellular enzymatic activity
- Macrophage phagocytosis
- Epithelial reabsorption into either lymph or blood
Describe the effect of pulmonary surfactant on surface tension:
Reduces surface tension from 70mNm to 10mNm
Creates the PV hysteresis
What does pulmonary surfactant do?
Reduces the tendancy for fluid to be sucked into the airspace (i.e from ECM)
How does surfactant influence hose defence?
Movement of particular matter towards ciliated regions is aided by surface tension gradients i.e (low in alveoli and higher in airways)
Both SP-A and SP-D act to bind pathogens to promote the action of macrophages in the immune response
What are the functions of pulmonary surfactant?
- Improves pulmonary compliance
- Aids fluids balance (removes from airspace)
- Host defence
Others:
- Reduces formation and maintenance of airway plugs
- Reduction of adhesion
- Aids in the hydration and rheology mucus
What is NRDS?
Neonatal resp. distress syndrome
- Lack of lung development i.e surfactant or airway development
