Development of the Lungs Flashcards
Which structure is the point of transition from upper to lower respiratory tract?
Larynx
What 3 layers comprise the trilaminar embryonic disc?
Ectoderm, mesoderm, endoderm
What are the lung stages and what weeks do they occur?
- Embryonic –> week 4-5 2. Pseudoglandular –> week 5-17 3. Canalicular –> week 16-25 4. Saccular –> week 24-40 5. Alveolar –> late foetal to 8 years
When does the lung bud appear?
Day 22
Where does lung bud originate from? How does it grow?
Originates as an outgrowth from the ventral wall of the foregut - Grows ventrocaudally, anterior to the gut tube - Eventually divides to form 2 lung buds
What are tracheoesophageal ridges? What is there purpose?
- Longitudinal mesodermal folds that form as respiratory diverticulum grows - Separate the respiratory diverticulum from the foregut (separates trachea and oesophagus)
What is the respiratory diverticulum? When does it appear?
A ventral outgrowth of foregut endoderm Embryonic period –> day 22
What are tracheoesophageal fistualas (TOF) caused by?
Disruption of the formation of the tracheoesophageal ridges leading to abnormal connection between trachea (respiratory portion) and oesophagus
How common are TOF?
1 in 3000-4500 live births
What is TOF often associated with?
A spectrum of mesodermal defects –> VA(C)TER(L)
What are 90% of TOF associated with?
Oesophageal atresia
What is oesophageal atresia?
Failure of development of the proximal part
Proximal (upper) oesophagus ends blindly (sac)
Distal (lower) part of the oesophagus communicates with the trachea via a fistula
What are prenatal/postnatal complications of TOF?
Prenatally:
- Too much amniotic fluid as foetus cannot swallow amniotic fluid
Postnatally:
- Stomach contents can enter lungs (infection)
- Air can escape into stomach so adomen rapidly distends as stomach fills with air
- Infant coughs/chokes due to inability to swallow
What is an H-type tracheoesophageal fistula?
Fistula between trachea and oesophagus –> rarer (only 4% of cases)
What are consequences of H-type Tracheoesophageal fistula?
- Milk (from oesophagus) may be driven into respiratory system (infection)
- Stomach contents can enter respiratory system
What are the mesodermal defects often associated with TOF?
Vertebral defects (spinal bifida)
Anal atresia (anal canal not formed correctly)
Cardiac defects (most common)
Tracheo-oesophageal fistulas
Esophageal atresia
Renal abnormalities
Limb defects
How do lungs form during pseudoglandular stage?
Tubular branching –> during partioning of oesophagus and respiratory diverticulum, right and left lung buds form
Describe the order of formation of bronchi during the pseudoglandular stage
Week 5:
- Trachea divides into 2 1ary bronchi (right and left)
- 1ary bronchi divide into 2ary bronchi (3 on right, 2 on left)
Week 6:
- 2ary bronchi branch, resulting in formation of 3ary bronchial buds (bronchial tree)
- By end of 7th week, the 18 bronchopulmonary segments have been established (10 right, 8 left)
- Branching continues to form terminal bronchioles by week 16
What does developing lung resemble during pseudoglandular stage?
Branched, compound gland of endodermal air-conducting tubules
Why do infants born during the Pseudoglanduar Stage not survive?
No alveoli so respiration is not possible
What is branching of respiratory tree to form 3ary bronchi caused by?
Signals between endoderm and mesoderm
Describe development of bronchi in canalicular period?
Terminal bronchioles start to give rise to respiratory bronchioles with some terminal sacs at the end (around week 24). These give rise to some alveolar ducts.
Describe vascularisation during canalicular period
Mesodermal tissues become highly vascularised (develop more capillaries)
Describe surfactant production during canalicular period
Surfactant production by type II pneumocytes begins arond week 20-22 but overall is not enough to prevent airways collapsing (atelactasis)
What is prognosis of infants born during canalicular period?
Still very poor but is chance of survival
What occurs to aid gas exhange during terminal sac period?
Further terminal sacs (primitive alveoli) develop and vascularisation increases dramatically.
Epithelium thins and capillaries come into ‘contact’ with epithelium –> diffusion is more efficient
What is the blood air barrier? When does it form?
Forms during terminal sac period
Exists in gas exchanging region of lungs (alveolar-capillary barrier or membrane)
- Prevents air bubbles from forming in blood and from blood entering alveoli
- Permeable to O2, CO2, CO etc
What are pneumocytes?
The surface epithelial cells of the alveoli
What are the 2 types of pneumocytes and what is their function?
Type I –> Gaseous exchange takes place
Type II –> Secrete surfactant
What happens when infant is born during terminal sac period?
Can survive but will likely need ventilation assistance –> may suffer from respiratory distress sydrome
What occurs during alveolar period?
Terminal sacs continue to develop into alveolar ducts with numerous alveoli. 95% of mature alveoli don’t develop until after birth
What is cartilage, smooth muscle, connective tissue and capillaires formed from?
Visceral mesoderm
What is purpose of surfactant?
Forms a film over internal walls of terminal sacs. Reduces surface tension and prevents alveolar from collapsing when there is low pressure.
What is respiratory distress syndrome and what is it caused by?
Inadequate surfactant:
- Surfactant protein B deficiency
- Inadequate production by type II pneumocytes
- Type II pnuemocytes haven’t developed enough
Where do lungs develop from?
Foregut endoderm
How does pleural cavity form?
At about 5 weeks, two longitudianl folds of the mesoderm called the pleuropericardial folds appear in the lungs and heart. These grow from the lateral body wall towards the midline to separate the pericaridal cavity (ventrally) and the pleural cavity (dorsally)
How does pleura form?
Formed from lateral plate mesoderm which eventually splits into visceral and parietal mesoderm layer
Visceral mesoderm –> forms visceral pleura
Parietal mesoderm –> forms parietal pleura
What is pulmonary agenesis?
Failure of primitive lung bud to split from bronchial buds leads to absence of lung tissue
What are the 2 types of pulmonary agenesis?
Unilater –> occurs on one side
Bilateral –> incompatible with life
What is clinical presentation of unilateral pulmonary agenesis?
- Respiratory distress
- Remaining lung is comprimised (lower respiratory tract infection)
- 60% have other congential abnormalities
- Agenesis of right lung is associated with higher frequency of anomalies
- Left agenesis –> enlarged right lung, deviation of heart and trachea
What is difference bewteen pulmonary aplasia and pulmonary agenesis?
- Lung parenchyma absent in both
- Short blind-ending bronchus in pulmonary aplasia
What is pulmonary hypoplasia? How does it differ from pulmonary aplasia?
Pulmonary aplasia is used to describe the incomplete development of lung parenchyma supplied by a rudimentary bronchus
Pulmonary hypoplasia is the incomplete development of the lungs, resulting in an abnormally low number or size of bronchopulmonary segments or alveoli. A congenital malformation, it most often occurs secondary to other fetal abnormalities that interfere with normal development of the lungs.
Pulmonary hypoplasia is distinguished by a normal tracheobronchial tree and underdeveloped pulmonary parenchyma.
What is congenital diaphragmatic hernia (CDH) and what is it associated with?
May be found in association with pulmonary hypoplasia.
- When diaphragm fails to close during prenatal development
- Contents from abdomen migrate into chest
- Can be fatal during development
What is branching morphogenesis? What is consequence of this?
Supernumerary (extra) lobes or segments. Little functional significance as cannot increase gas exchange from extra lobe
How can mechanical ventilation during premature birth lead to RDS?
Damage to alveolar lining as fluid and serum proteins leak into alveolus. Continued injury may lead to detachment of alveolar lining.
Chronic lung injury in preterm infants may cause bronchopulmonary dysplasia (abnormal formation)
What is treatment for RDS?
- Glucocorticoid (steriod) treatment:
- Accelerates foetal lung development and surfactant production
- Must be given prior to birth
- Surfactant therapy
- Natural or artificial surfactant
- Surfactant A and B proteins more effective
What is sufactant protein B deficiency disease?
Genetic - autosomal recessive
Fatal disease even with surfactant replacement therapy (only temporary)
What is agenesis?
The failure of an organ to develop during embryonic growth and development due to the absence of primordial tissue
What is aplasia?
The failure of an organ or tissue to develop or to function normally.
