Next Lesson - Ventilation and Lung Mechanics
Core
The respiratory system can be divided based on anatomical location into the upper and lower systems:
- The upper airway is made up of the nasal cavity, oral cavity, pharynx and larynx.
- The lower airway is made up of the trachea, bronchi, bronchioles and alveoli.
Sources disagree about where the upper airway ends and the lower airway begins. For example, some sources place the larynx in the lower airway instead of the upper airway.
More helpfully for understanding physiology, the airway can also be divided based on function into the conducting portion and the respiratory portion:
- The conducting portion includes the trachea, bronchi and bronchioles up to and including the terminal bronchioles (the last, smallest conducting airways, which have no alveoli). The upper airway (the nasal cavity, oral cavity, pharynx and larynx) also belongs to the conducting portion, because it takes no direct part in gas exchange. The conducting portion warms, moistens and conducts air to the respiratory portion. Respiratory bronchioles belong to the respiratory portion.
- The respiratory portion is made up of the respiratory bronchioles, alveolar ducts (the small passages leading from the respiratory bronchioles to the alveoli) and alveoli, and is the site of gas exchange.
The respiratory system begins development from an outpouching of the primitive gut tube known as the respiratory diverticulum. This structure is derived from the endoderm (the innermost embryonic layer) of the primitive gut tube. The gut tube is created by folding of the embryo and will go on to develop into the gastrointestinal tract.
The outpouching occurs from the foregut (the cranial end of the gut tube) and its outer surface is covered with mesoderm (the middle embryonic layer).
As it is an outpouching, the respiratory diverticulum is continuous with the gut tube at the start of the development. To allow the formation of two separate systems, a tracheoesophageal septum forms.
By the end of week 4, the respiratory diverticulum splits into two bronchial buds (the left and right lung buds). These give rise to the branching airways. The airway and alveolar epithelial lining develops from endoderm; the surrounding mesoderm contributes supporting tissues, including connective tissue, smooth muscle and pulmonary vessels.
Diagram - The development of the lungs from the beginning of week 4 to week 8 after conception
SimpleMed original by Dr. Maddie Swannack
A tracheoesophageal fistula is an abnormal connection between the trachea and the oesophagus.
During development in the womb, the respiratory diverticulum and the foregut start out continuous. A fistula forms if there is a defect in the formation of the tracheoesophageal septum, because the connection between them then persists.
There are multiple different types, which are shown in the simplified diagram below.
Diagram - The 5 types of oesophageal atresia (the oesophagus ends in a blind pouch) and tracheoesophageal fistula, using the Gross classification (a system that gives each of the five types a letter). Type C, where the upper oesophagus ends blindly and the lower oesophagus joins the trachea, is the most common by far.
SimpleMed original by Dr. Maddie Swannack
This stage is known as the Pseudoglandular Stage. The week ranges for the stages are approximate, and sources give slightly different ranges. Stage timings are often given in weeks after conception (when the egg is fertilised). Gestational age is used later for survival and steroid advice. It is counted from the first day of the mother's last period, about two weeks before conception, so it runs about two weeks ahead.
The conducting portion of the airways continues to develop by repeated branching. This forms bronchioles (the small airways that branch from the bronchi) from the tertiary bronchi (the third-level branches) that had formed by the end of week 8. By the end of this stage all of the conducting airways have been laid down.
During the pseudoglandular stage, branching epithelial tubes are surrounded by mesenchyme (loose embryonic connective tissue that comes from mesoderm), but gas-exchanging alveolar structures have not yet formed. The cells lining the airways (the respiratory epithelium) are endodermal in origin, with surrounding mesodermal support; the lungs are not yet capable of gas exchange.
This stage is known as the Canalicular Stage.
Throughout this ten-week period the respiratory bronchioles develop by budding off the bronchioles formed during the pseudoglandular stage. The respiratory bronchioles are the first structures in the respiratory portion of the airway.
As the alveoli (air sacs) have not yet developed enough, there is only a very limited gas exchange surface. Towards the end of this stage some gas exchange becomes possible, and the chance of survival with intensive neonatal (newborn) care rises quickly with each week of pregnancy. In England and Wales in 2020 to 2021, about 12 in 100 live-born babies born at 22 weeks of gestation (weeks of pregnancy) survived to be discharged from neonatal care. The figures were about 40 in 100 at 23 weeks and 69 in 100 at 24 weeks. In the UK, survival-focused care (care aimed at saving the baby's life) is not offered before 22 weeks of gestation. For babies born from 22 to 26 weeks, the decision depends on an assessment of each baby's risk of dying or of severe disability, not on gestation alone.
This stage is known as the Terminal Sac Stage.
The alveoli begin to develop around 26 weeks. Within the alveolar walls, there are two main cell types which arise:
- Type I Pneumocytes (type I alveolar cells) are thin squamous epithelial cells (squamous means flat) covering most of the alveolar epithelial surface area, providing a short diffusion distance for gas exchange.
- Type II Pneumocytes (type II alveolar cells) are cuboidal epithelial cells (cube-shaped) that produce surfactant. Surfactant production normally begins between weeks 24 and 28 of pregnancy, and most babies make enough to breathe normally by week 34. In a baby born before then, the amount may be too small to keep the alveoli open after birth.
Surfactant is made up of a mix of phospholipids and proteins, and plays a key role in reducing surface tension in the lung. Surfactant has a hydrophilic (water-attracting) end and a hydrophobic (water-repelling) end, so it lines the surface of the thin layer of fluid inside the alveoli and reduces the surface tension there. With less surface tension, the alveoli are able to expand at smaller pressures. See our article on ventilation and lung mechanics for more information about surfactant.
From as early as the first trimester (the first three months of pregnancy) and through the second and third trimesters, the fetus also ‘practises’ breathing movements, which can be seen on ultrasound. The fetus will inhale and exhale amniotic fluid (the fluid that surrounds it in the womb). This helps to condition the breathing muscles for life, and helps to encourage the growth and development of the lungs.
Newborn respiratory distress syndrome can occur when the lungs produce insufficient surfactant, particularly after premature birth. Surfactant production may already have begun, but the amount made may not yet be enough to keep the alveoli open.
Without the surfactant, the alveoli need higher pressures to expand. The baby cannot easily generate these pressures, resulting in difficulty breathing and signs of respiratory distress. If preterm birth is likely, the mother may be given glucocorticoids (steroids). These stimulate the production of surfactant in the fetus and improve breathing after birth. NICE advises offering them between 24+0 and 33+6 weeks of pregnancy (24 weeks and 0 days to 33 weeks and 6 days) and considering them between 34+0 and 35+6 weeks. At 22+0 to 23+6 weeks, the woman and her care team discuss whether to use them.
Edited by: Dr. Ben Appleby
Reviewed by: Dr. Thomas Burnell and Dr. Marcus Judge
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