Table of Contents
Page created on August 13, 2020. Not updated since.
Learning objectives
- Which structure buds out from the foregut and which tissues does it give rise to?
- During which week does the respiratory diverticulum appear?
- What separates the trachea from the oesophagus?
- Where do the laryngeal muscles and cartilages originate from?
- Describe the formation of the bronchial tree
- Describe the origin of the pleura
- What are the four periods of lung maturation?
- What is the function of type II pneumocytes, and when do they appear?
- Describe the postnatal maturation of the lungs
- What are the foetal breathing movements, and why are they important?
- What happens to the fluid in the lungs during birth?
- What is neonatal respiratory distress syndrome?
- What is pulmonary hypoplasia, and what is the most common cause?
- What is a bronchogenic cyst?
Development of the respiratory system
During week 4, an outgrowth appears on the ventral wall of the foregut. This outgrowth is the respiratory diverticulum, also called the lung bud. The endoderm of this diverticulum will give rise to the epithelium of the whole lower respiratory tract, from the larynx to the alveoli. The cartilage, muscle, and connective tissue originates from splanchnic mesoderm surrounding the foregut.
Separation of the oesophagus and the trachea
As discussed in the previous topic, the tracheoesophageal septum will separate the respiratory diverticulum from the rest of the foregut, essentially separating the future trachea from the future oesophagus. The trachea remains connected with the pharynx through the laryngeal orifice.
Development of the larynx
The laryngeal muscles and cartilages originate from mesenchyme of the fourth and sixth pharyngeal arches. This explains why the laryngeal muscles are innervated by branches of the vagus nerve, the superior and recurrent laryngeal nerves, respectively. The epithelium originates from endoderm of the respiratory diverticulum, as already described.
After the lumen of the larynx becomes temporarily occluded, a couple of lateral recesses develop: the laryngeal ventricles. The tissue surrounding these ventricles differentiates into the true and false vocal cords.
Development of the trachea and bronchi
After being separated from the foregut, the respiratory diverticulum forms the trachea. Two buds, one on each side, grow laterally from the base of the respiratory diverticulum. These buds are the primary bronchial buds. Each bud will give rise to a primary bronchus. The right primary bronchus forms three secondary bronchi, while the left one forms two.
The bronchial tree continues to form from there. By the end of the sixth month, approximately 17 generations of subdivisions have formed. Another six generations of divisions occur postnatally.
Development of the lungs
As the bronchial tree develops, the lungs form and grow. The spaces for the lungs, the pericardioperitoneal canals, are narrow. Eventually, the pleuroperitoneal and pleuropericardial folds will separate the space the lungs lie in from the peritoneal and pericardial cavities, forming the pleural cavity. The visceral pleura originates from splanchnic mesoderm, while the parietal pleura originates from somatic mesoderm.
Maturation of the lungs and alveoli
During weeks 5 – 16, the lungs are in the pseudoglandular period, so called because the epithelium resembles glandular epithelium. During this phase the bronchial tree is branching, but no respiratory bronchioles or alveoli are present.
The canalicular period occurs during weeks 16 – 26. During this period, respiratory bronchioles and alveolar ducts are formed.
The terminal sac period lasts from weeks 26 until birth. During this period, alveolar (or terminal) sacs, containing alveoli, form. The alveoli are in close contact with capillaries. At the end of the sixth month, type II pneumocytes develop, and begin to produce the surfactant. This surfactant reduces the surface tension in the alveoli, preventing them from collapsing. Without surfactants the alveoli would collapse during expiration. Surfactant production increases significantly in the two weeks before birth.
The last period, the alveolar period, overlaps slightly with the terminal sac period and lasts for years after birth. Beginning from month 8 and lasting until childhood, the epithelium thins, establishing the very thin blood-air barrier. More alveoli are formed. It’s estimated that only 1/6th of the adult number of alveoli are present during birth, which illustrates the magnitude of maturation which occurs postnatally.
At the beginning of month 8, at around week 30, there are enough mature alveoli and capillaries for a premature infant to survive. The probability of uncomplicated premature birth increases rapidly, from 20% to almost 100%, during weeks 22 – 32, as the lungs rapidly mature further.
What do the lungs contain before birth?
Foetal breathing movements, originating at the diaphragm, begin as early as week 10. These movements are important for stimulating lung development, and for conditioning the respiratory muscles. During these movements amniotic fluid is aspirated, but this is not a problem. Type II pneumocytes begin producing surfactant at around month 7, which will remain in the amniotic fluid inside the lungs.
After birth, the lung fluid is rapidly absorbed by blood and lymph capillaries. The surfactant is not absorbed but will remain as a thin coat on the type I pneumocytes, decreasing the surface tension when the first breath of air enters.
Molecular regulation of respiratory development
The signalling molecule retinoic acid (RA) is important in development of the respiratory diverticulum. RA upregulates the transcription factor TBX4.
Interactions between respiratory diverticulum endoderm and the surrounding splanchnic mesenchyme drive the formation of the bronchial tree. The mesenchyme produces fibroblast growth factors (FGFs), which drive the branching.
Malformations
Neonatal respiratory distress syndrome
Neonatal respiratory distress syndrome (NRDS) is a potentially deadly disease which occurs mostly in premature infants. The incidence of NRDS is lower in older premature infants than younger. Because significant surfactant production occurs relatively late in foetal life, premature infants are at high risk for not having enough surfactant.
If this is the case, the alveoli will collapse during expiration, a process called atelectasis. This prevents proper oxygenation, causing hypoxaemia and hypercapnia in the infant.
NRDS is not a disease exclusive to premature infants, as even full-term births may have insufficient surfacant. Maternal diabetes mellitus and delivery by C-section are also risk factors for development of NRDS, even in full-term births.
Congenital diaphragmatic hernias and pulmonary hypoplasia
Pulmonary hypoplasia refers to underdevelopment of the lungs. It’s characterised by abnormally low number of alveoli and small airways. The most common cause of pulmonary hypoplasia is a congenital diaphragmatic hernia. In this form of hernia, intraabdominal organs herniate through the diaphragm and into the pleural cavity.
The presence of intraabdominal organs in the pleural cavity give the lungs limited space to develop, causing the hypoplasia. This most commonly occurs on the left side, as the right side of the diaphragm is protected by the liver.
There are many causes of congenital diaphragmatic hernia, the most common of which is due to failure of fusion of the septum transversum with the pleuroperitoneal membranes on the postero-lateral aspect.
Bronchogenic cysts
Sometimes, certain bronchi dilate and form cysts inside the lung. These bronchogenic cysts are often not drained properly, making them predisposed to becoming infected postnatally.
Summary
- Which structure buds out from the foregut and which tissues does it give rise to?
- The respiratory diverticulum (lung bud), which gives rise to the epithelium of the whole lower respiratory tract
- During which week does the respiratory diverticulum appear?
- Week 4
- What separates the trachea from the oesophagus?
- The tracheoesophageal septum
- Where do the laryngeal muscles and cartilages originate from?
- From the fourth and sixth pharyngeal arch mesenchyme
- Describe the formation of the bronchial tree
- Primary bronchial buds sprout from the respiratory diverticulum and form the primary bronchi
- The rest of the bronchial tree grows from branching of the primary bronchi
- Describe the origin of the pleura
- The visceral pleura originates from splanchnic mesoderm
- The parietal pleura originates from somatic mesoderm.
- What are the four periods of lung maturation?
- Pseudoglandular period (weeks 5 – 16)
- Canalicular period (weeks 16 – 26)
- Terminal sac period (week 26 – birth)
- Alveolar period (month 8 – childhood)
- What is the function of type II pneumocytes, and when do they appear?
- They produce surfactant, which reduce surface tension in the alveoli and prevent them from collapsing
- They appear at the end of month 6
- Describe the postnatal maturation of the lungs
- Postnatally the bronchial tree undergoes six more generations of divisions, and many more alveoli are formed
- What are the foetal breathing movements, and why are they important?
- These movements originate at the diaphragm and are important for stimulating lung development and for conditioning respiratory muscles
- What happens to the fluid in the lungs during birth?
- It’s absorbed into the blood and lymph
- The surfactant in the fluid remains as a coat on the alveoli
- What is neonatal respiratory distress syndrome?
- A disease caused by insufficient surfactant, causing collapse of alveoli with subsequent impaired oxygenation
- It mostly occurs in premature infants
- What is pulmonary hypoplasia, and what is the most common cause?
- Pulmonary hypoplasia refers to underdeveloped lungs with low number of alveoli and small airways
- It’s most commonly caused by a congenital diaphragmatic hernia, which compresses the foetal lungs and prevent them from growing
- What is a bronchogenic cyst?
- It’s a result of abnormal dilation of a bronchus, forming a cyst
- These cysts can become infected postnatally