Cardiorespiratory Adaptation At Birth I
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What are the 5 stages of lung development?
• Embryonic • Pseudoglandular • Canalicular • Saccular • Alveolar
Describe the embryonic phase
• @ 3-6 weeks • Respiratory diverticulum develops off esophagotracheal ridge • Lung bud develops from foregut • This all turns into resp tract • Trachea develops with its 2 lung buds as bifurcation occurs • Further development of airways -> next stage
Describe the pseudoglandular phase
• @ 6-17 weeks • Branching in lungs to form terminal bronchioles • Airways still closed however as no lumen • No respiratory bronchioles, no alveoli present (yet)
Describe the canalicular phase
• @ 17-26 weeks • Each terminal bronchiole divides into 2+ respiratory bronchioles • “Canunlate” - open holes, to breathe through, tubes
Describe the saccular phase
• @ 27 weeks -> term • Respiratory bronchioles divide into 2-3 alveolar ducts • These develop terminal sacs • Capillaries establish close association
Describe the alveolar phase
• From term -> childhood • Mature alveoli w/ well-developed epithelial-endothelial association
Which growth factors are involved in lung development?
• Hepatocyte nuclear factor 3beta - foregut • FGF-10, Sonic hedgehog, BMP4 - outgrowth of new end buds • Gli proteins - branching • Vascular endothelial growth factor (VEGF) - angiogenesis
When do the saccules start to develop?
Around 24 weeks
What develops around each saccule and what causes this?
Capillaries - caused by VEGF
Most alvolar development occurs post-term. By what age will there be adult numbers of alveoli?
• 4 years • Mainly by growth in number
When are pneumocytes present?
• Type 1 and type 2 • Present at 22 weeks
What do lamellar bodies do and when are they present from?
• From 24 weeks • Store surfactant
In terms of structural pathology, how does the time of onset impact alveoli?
• < 16 weeks, branching irreversibly affected, potentially permanent reduction in number of alveoli • > 16 weks, branching complete, predominantly alveolar numbers affected
Give examples causing extrinsic restriction in terms of lung development
• Congenital diaphgragmatic hernia • Effusions • Thoracic or vertebral abnormalities
Give an example causing intrinsic restriction of lung development
• Lung cysts (cystic adenomatoid malformation)
Apart from time of onset and restriction, what other (lifestyle) factors affect lung development?
• Malnutrition (vit A) • Smoking Affect peak flow, alveolar number + lung size
Fetal lungs are filled with liquid, what is the content of lung liquid?
• High sodium (150) • High chloride (157) • Low potassium (6.3) • Low bicarbonate (2.8) • Low protein (0.03)
Describe lung liquid secretion
• Secondary active transport of Cl from interstitium to lumen • Sodium and water follow • Liquid production allows for positive pressure of 1cmH2O
Why is lung fluid required?
• For lung growth • Not for branching • Interruption of lung liquid secretion -> abn dpmt
How is lung liquid absorbed?
• Active sodium transport in apical membranes • Labour & delivery: adrenaline release -> reduced secretion + resorption begins • Thyroid hormone + cortisol required for maturation of fetal lung response to adrenaline • Exposure to postnatal oxygen increases sodium transport across pulmonary epithelium
How does oligohydramnios result in abnormal lung development?
• Reduced amniotic fluid surrounding fetus • Kidney abnormalities + early rupture • Abnormally developed lungs - die from lung problems
Fetal breathing slows liquid loss - maintains expansion. What conditions can result in fetal breathing abnormalities?
• Neuromuscular disorders • Phrenic nerve agenesis • Congenital diaphragmatic hernia
What is TTN (transient tachypnoea newborn) and how does it come about?
• Newborn presenting with abnormally rapid breathing + resp distress, should settle in 6-12 hours • Due to lack of lung liquid clearing • Due to delivery without labour - so by elective caesarean section - lack of adrenaline + cortisol, which is important for lung liquid absorption
Pulmonary surfactant is key to sustaining life post-natally. Where is surfactant produced, stored and degraded?
• Produced by type 2 pneumocytes: surfactant phosphatidylcholine prod in endoplasmic reticulum • Stored in lamellar bodies • Absorbed and recycled (>90%) by alveolar cells • Turnover time 10 hours