16. Lung Development Flashcards
What are the 4 phases of intrauterine lung development?
• Embryonic (0-7 weeks) - tracheal bud forms from the foregut (week 4-5) - main bronchi • Pseudoglandular (5-17 weeks) - conducting airways - bronchi and bronchiole - morphogenesis into mesenchyme - development of cartilage, glands and smooth muscle • Canalicular (16-27 weeks) - respiratory airways - blood gas barrier starts to develop (thinning epithelium) - epithelial differentiation (Type I and II) • Saccular/Alveolar (28-40 weeks) - alveoli appear - surfactant detectable - infant becomes viable
What happens to the lungs postnatally?
- Alveoli multiply and enlarge in size with chest cavity
* Development into adolescence
How do the lungs heal from pneumonia in children compared to adults?
- Children - reversible effect, should return to normal due to continuous development
- Adults - tend to scar
What is vasculogenesis and how does it occur?
- Forming of the blood vessels
- Occurs along the frame that the airways create
- Develop in the canalicular phase
- Pulmonary artery branching follows bronchial branching (week 16)
What is a hypoplastic lung and how can it be seen?
- Interruption to bronchial branching
- Development of a small lung with little branching
- Isotope ventilation scan - poor air supply to the lung
- Isotope perfusion scan - poor artery development
How many lungs have after 56 days of development?
- 3 lobes on the right
* 1 lobe on the left
Describe the mechanism of formation of alveolar walls
• Saccule Wall
- epithelium on both sides with double capillary network
- myofibroblasts and elastin fibres at intervals in the wall
• Secondary septa develop from the wall led by elastin produced by the myofibroblast
- capillary lines both sides with matrix between
• Capillaries have coalesced to form one sheet alveolar wall
- thinner and longer with less matrix
- muscle and elastin at the tip
• Process continues into the 3rd trimester - larger SA
• Continues into life
What is primary ciliary dyskinesia?
- aka Kartagener’s syndrome
- Malfunction in movement
- Right lower lobe collapse
- Dextrocardia
- Possible total situs inversus
- Absence of outer and inner dynein in cilia
What is laryngomalacia?
- Incomplete rings posteriorly in larynx
- Irregular plates
- Calcify with age
- Malacia - softening of the airway so its prone to collapse ( => occlusion)
- Malcic segment - localised
What is agenesis and what causes it?
- Complete absence of the lung and vessel
- Very rare
- Interrupted blood flow in first month of development
What is aplasia?
Blind ending of bronchus (no lung or vessel associated with it)
What is hypoplasia and what causes it?
• Bronchus and rudimentary lung are present
• Reduced in size and number
• Usually secondary and caused by a lack of space
• Intrathoracic or extrathoracic
- caused by hernia of diaphragm, chest wall pathology, oligohydramnios, lymphatic/cardiac mass
• Lack of growth, caused by:
- congenital thoracic malformation
- Cystic Pulmonary Airway Malformation (CPAM/CCAM) (defect in pulmonary mesenchyma, normal blood supply)
- Type 2 CCAM - multiple cysts
• Congenital Large Hyperlucent Lobe
- progressive lobar expansion
- cartilage fails and results in a one-way valve like effect
- extrinsic compression, alveoli expand
• Intralobar sequestration
- abnormal segment share of visceral pleura
- abnormal blood supply
- lower lobe is more common
What can “insults” to the dividing bronchus lead to?
- Agenesis (early malfunction)
- Local lesion
- Malformation of systemic supply
- Malformation in the lung
How does a pregnant mother smoking affect the development of a child’s lung?
- Increased respiratory movements and changes in thoracic pressures
- Removed soft tissue support and interstitial tissue development
- Reduced elasticity of alveoli
- Reduced airway diameter
- Reduced support - wheezy infant
- COPD at old age
What is special about the cells at the tips of the buds in lung development?
• Epithelial cells at tips
- highly proliferative multipotent progenitor cells
- differentiate into a wide range of cells
- depending on different growth factors
• Cells behind the tip divide and differentiate into the various cell types
What are the different growth factors involved in lung development?
Inductive
• FGF - branching morphogenesis
• EFG - epithelial proliferation and differentiation
- e.g. VEGF - surrounds the lung bud, induces differentiation in the mesenchyme, coalesce to form capillaries, airways act as a structural guide
Inhibitory
• TGF-beta - matrix synthesis and surfactant production, inhibits the proliferation of epithelium & blood vessels
• Retinoic acid - inhibits branching
What is primary and terminal apnoea and how is it dealt with?
- Failure of attempted breathing at birth (could be umbilical strangulation)
- Terminal apnoea - 2nd attempt with failure - decreased blood pressure, maintained heart rate
- Resuscitation - if delivery of oxygen fails following terminal apnoea. Results in an increase in heart rate and BP.
- Apgar score - determines severity of apnoea and need for resuscitation
How does the lung develop following birth?
• Loss of alveolar elasticity - reduced compliance
• Similar elasticity in infants and elderly (increased susceptibility to problems)
• Lung function increases to a point, then decreases with age
• Respiratory diseases increase the reduced function later in life
• Increased birth weight - increased lung function in adult life
- premature babies - increased risk of reduced lung functio
What are the lungs like at birth?
- Small volume relative to body weight
- All airways differentiated
- 33-50% of the alveoli present
- Most arteries and veins present
What are the mechanisms to increase flow after birth?
• Expansion of alveoli causes dilation of arteries
- stimulates release of NO
- NO and PGI2 can also be used as synthetic dilators
• Vasoconstrictor inhibitors present from foetal life
• Oxygen is the final stimuli - relaxes the smooth muscle
• Airway resistance falls
• Lung compliance rise takes 24 hours
• Lymphatic system removes fluid filling lungs - lungs remain stiff until this is done
How do the blood vessels change at birth?
- Decrease in pulmonary vascular resistance
- 10-fold rise in pulmonary blood flow
- Rapid increase in arterial lumen diameter and wall thins (maintained through artery growth)
- Chemo-receptors and respiratory centre reset
- Change in cell shape and cytoskeletal organisation
Describe the circulation in a foetus
- Mostly bypasses the lungs
- Placenta => right atrium => right ventricle or left atrium (through foramen ovale)
- Some goes from the right ventricle to the lung (via pulmonary trunk)
- Most goes from the right ventricle to the aorta (via the ductus arteriosus) as pulmonary artery pressure > systemic artery pressure
How does circulation change at birth?
- Massive CNS stimulation due to change in environement
- Low pressure placental circulation cut => rise in systemic arterial pressure
- Lung aeration => fall in pulmonary arterial pressure (as lungs stretch)
- Increased PO2 and decreased PCO2
- Ductus arteriosus closes due to changes in prostaglandings
- Foramen ovale closes due to increase in left atrial pressure (due to rise in systemic arterial pressure)
What happens to the surfactant in a foetus?
• Once secreted by the lamellar bodies, these bodies create a force resulting in distension, keeping the airways open at lower pressures
• Generated in late 2nd/early 3rd trimester - premature babies at risk of alveolar collapse
• Idiopathic respiratory distress syndrome: alveolar collapse => hypoventilation and hypoxic acidosis => pulmonary vasoconstriction
- baby grunts to try and raise pressure
- continuous ventilation required but surfactant can be replaced
How can lung function be measured?
- Forced expiratory measurements made using a pneumotachograph
- Change in flow-volume loop
