Development of the Respiratory Tract
Overview
Like many other organ systems, the respiratory system develops through interactions between mesoderm and another germ layer, in this case endoderm of the developing gut tube.
Mesoderm in the region of the foregut increases production of retinoic acid (RA) that up regulates a transcription factor in endoderm of the gut tube to stimulate formation of a ventral respiratory diverticulum.
The endoderm of the respiratory diverticulum forms:
- epithelium lining the respiratory tract
- type I pneumocytes
- type II pneumocytes
The surrounding mesoderm forms:
- CT
- cartilaginous rings and plates
- smooth muscle components of the airway
- macrophages
- pleura
In this 5 week old embryo we can see certain external features that demonstrate concurrent development of many organ systems. Note the presence of the developing eye and ear, upper and lower limb buds and the pharyngeal arches that contribute to the development of the head and neck.
Roll over the image to see a deeper layer.
Inside the embryo, we can see emergence of the lung bud as a ventral outgrowth of the foregut endoderm.
Development of the respiratory system involves three major processes:
- Branching
- Differentiation
- Maturation
Branching
Development of the respiratory system involves continuous branching of the respiratory diverticulum, a process that begins in the embryo and continues into the 10th postpartum year.
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At the point of origin of the respiratory diverticulum, the foregut pinches inward to separate the gut tube from the respiratory diverticulum by development of a tracheoesophageal septum. Failure of the septum to develop results in tracheoesophageal fistulas sometimes associated with atresia of the esophagus.
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Think of the gross anatomy of the lung when looking at the branching pattern. By day 26, the respiratory diverticulum had divided into right and left bronchi and by day 28 the lobar bronchi appear.
Recall that the left lung has two lobes while the right lung has three.
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Lobar bronchi are present by week 5, when there is an upper lobe bronchus and a lower lobe bronchus in the left lung and an upper lobe, middle lobe and a lower lobe bronchus in the right lung.
By six weeks, tertiary bronchi begin to appear. These form the basis of the bronchopulmonary segments, the functional anatomical units of each lung. We generally identify 10 bronchopulmonary segments in each lung.
Differentiation
Differentiation results in the conversion of cuboidal epithelium lining the respiratory passages to a thinner simple squamous epithelium closely associated with capillaries to form an air-blood interface for the exchange of gasses between the alveoli and blood.
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Canalicular Period
The pseudoglandular period, roughly between 5 to 16 weeks of development is characterized by prolific branching of the airway to form terminal bronchioles.
The canalicular period is between 16 and 26 weeks of development is characterized by formation of respiratory bronchioles and alveolar ducts lined with simple cuboidal epithelium. Late in this period, there is thinning of some regions of cuboidal epithelium to form primitive alveoli.
Numerous capillaries, of mesodermal origin, form within the stroma of the lung tissue surrounding the bronchioles. -
Terminal sac stage is roughly 26 wk until birth and is characterized by proliferation of alveoli and alveolar ducts. Capillaries abut against the alveolar epithelium to form the blood/air interface that facilitates exchange of gasses in the lung.
Cells in the wall of the alveoli, particularly when in association with the capillaries, thin to form type I pneumocytes. Type II pneumocytes also begin to develop and to secrete surfactant.
Late in the 7th month, there are enough alveoli formed so that survival is possible if the baby is born at this time.Terminal Sac Stage
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Alveolar Period
The alveolar period begins before birth and continues into the 10th year postpartum. It is characterized by continued proliferation of the alveoli and further maturation of the blood air interface. This interface is referred to as the alveolocapillary membrane and consists of:
- type I pneumocytes
- capillary endothelial cells
- their fused basal laminae
There is also further development of the type II pneumocytes and continued production of surfactant.
Maturation
This is an enlarged view showing the components of the alveolocapillary membrane, the air/blood interface.
It is formed by:
- type I pneumocyte
- basal lamina
- capillary endothelium
This is the thinnest interface between the air and blood and facilitates movement of oxygen from the alveoli to bind with hemoglobin in the red blood cells and the passage of carbon dioxide from the blood to the alveoli for expiration.
Roll over the image to see how similar this arrangement is to the interface between maternal and fetal blood in the placenta.
Alveolocapillary Membrane
Lungs and Pleura
Endoderm (yellow) forms the lining epithelium of the respiratory passages.
Mesoderm (red) forms the stroma of the lungs and the pleural membranes.
The visceral pleura extends into the fissures of the lung and is derived from the splanchnic mesoderm covering the lung buds. At the root of the lung, the visceral pleura is reflected onto the parietal pleura lining the inside of the chest cavity.
The parietal pleura is named for the surfaces that it covers; costal pleura for that in contact with the ribs and intercostal muscles, diaphragmatic pleura for that on the diaphragm and mediastinal pleura for that facing the mediastinum. Cervical pleura extends into the base of the neck to cover the apex of the lung.
Clinical Correlates
Tracheoesophageal Fistula & Atresia
Esophageal Atresia
Esophageal atresia accounts for >90% of anomalies of the upper airway and gut tube. Esophageal atresia is usually accompanied by tracheoesophageal fistula distally. These defects are also often associated with additional defects of cardiac development.
Esophageal atresia results in polyhydramnios due to the inability of the fetus to swallow amniotic fluid. Continuity between the proximal and distal segments of the esophagus is generally done in the immediate post partum period.
The presence of a looped ng tube demonstrates the level of termination of the proximal segment of the esophagus.
Tracheoesophageal Fistula
Tracheoesophageal fistulae result from failure of the tracheoesophageal septum to completely separate the respiratory diverticulum from the foregut during early development. Consequently, patentcy is maintained between trachea and esophagus.
In the image, barium swallowed by the neonate fills both the esophagus and trachea and the fistula between them.
Congenital Cysts
Congenital cysts (congenital lobar overinflation) results in enlargement of one or more lobes of the lung leading to overinflation. The patient may not experience respiratory distress. In the case of a 2 month old infant in this instance, overinflation of the left lung has resulted in shifting of the mediastinal contents (heart, trachea, esophagus and related vessels) to the right, with compression of the right lung.
Parturition
Parturition or birth may be coordinated with maturation of the lungs. As the lungs mature, production of surfactant increases and may possibly influence the timing of onset of parturition.
Beginning with the yellow callout, read around in a counterclockwise direction