Development of the Respiratory System

Written by Sam Barnes

Last updated May 20, 2024 • 15 Revisions •

The function of the respiratory system can be divided into two parts: the conducting portion and the respiratory portion. The conducting portion conveys, moistens, and warms the air from outside the body as it makes its way to the lungs. The exchange of gas occurs at the respiratory portion.

Structurally, the respiratory system is divided into the upper and lower respiratory tracts/systems. The upper respiratory system consists of the nasal cavity, oral cavity, pharynx and their associated structures.

The lower respiratory system consists of the trachea, bronchi, bronchioles and alveoli. It develops relatively late in the embryo – which can cause problems when babies are born prematurely.

In this article, we will discuss the development of the respiratory tract and its clinical correlations.

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Initial Development

The respiratory system is derived from the primitive gut tube – the precursor to the gastrointestinal tract. The gut tube is an endodermal structure which forms when the embryo undergoes lateral folding during the early embryonic period.

At approximately week 4 of development, an out-pocketing appears in the proximal part of the primitive gut tube (the foregut) – this is known as the respiratory diverticulum. 

Initially, the respiratory diverticulum is continuous with the foregut; but this is not functionally suitable. The formation of a longitudinal ridge known as the tracheoesophageal septum rectifies this to make the two structures compatible with life.

The diverticulum bifurcates into two buds, which become the left and right primary bronchi. The primary bronchi then proliferate to give rise to secondary and tertiary bronchi.

Fig 1
Initial development of the lower respiratory tract.

Clinical Relevance

Tracheoesophageal Fistula

A tracheoesophageal fistula is a direct connection between the trachea and the oesophagus. It can arise as a complication of surgical procedures or can be congenital.

Congenital cases occur if the tracheoesophageal septum fails to form fully, or forms abnormally – and leaves the trachea in continuity with the oesophagus. Common abnormalities include:

  • Oesophagus empties into the trachea
  • Oesophagus is blind ended proximally and arises from the carina distally

The presentation therefore varies. The infant may become cyanosed during feeding or may vomit/regurgitate food. Management is usually through the surgical resection of the fistula, and the anastomosis of any discontinuous segments.

Fig 2
Common types of tracheoesophageal fistulae.

Ongoing Development

Pseudoglandular Stage: Weeks 8-16

Each bronchopulmonary segment will become a specific portion of the lung, carrying its own tertiary bronchus and branches of the bronchial and pulmonary arteries. During weeks 8-16, the ducts develop within bronchopulmonary segments. Bronchiolar buds branch off from the tertiary bronchi and begin to proliferate.

At this stage, as there are no alveoli, there is no gas exchange – and so the lungs are unable to oxygenate blood. However, the lungs are a metabolically active, developing tissue, which means they are able to remove large amounts of oxygen from the blood

In order to stop the lungs from starving the body of oxygen, the ductus arteriosus shunts blood from the pulmonary artery directly to the aortic arch. This closes at birth in the vast majority of people.

During this stage, the lungs resemble the development of tubuloacinar glands – hence the name.

Canalicular Stage: Weeks 16-26

Throughout the canalicular stage, the respiratory bronchioles develop, budding off from the terminal bronchioles formed within the pseudoglandular stage.

Despite this, there is still no gas exchange membrane, and so the lungs are not yet functional. Therefore, the prognosis for vast majority of babies born during this stage is not high.

Terminal Sac Stage: Week 26 onwards

From week 26 onwards, the alveoli develop. Within these alveoli there are two types of cell:

  • Type I pneumocytes – basic simple squamous epithelial cells, which comprise 90% of the alveolus.
  • Type II pneumocytes – simple cuboidal cells which comprise the remaining 10% and are responsible for the production of surfactant.

Surfactant is amphipathic, meaning it is able to bind to both hydrophobic and hydrophilic molecules simultaneously. In this case, surfactant binds to water and air within the alveoli. This has the effect of reducing the surface tension. As a result of the reduced surface tension, the alveoli are able to expand to greater volumes at a given pressure.

Simply put, surfactant allows us to expand our lungs with minimal effort.

Clinical Relevance

Respiratory Distress Syndrome

If a baby is born prior to the development of type II pneumocytes, they will be unable to produce surfactant. As a result, they will have difficulty expanding their lungs to take their first breath.

If a pre-term delivery is unavoidable or inevitable, the mother can be given glucocorticoids to stimulate surfactant production in the fetus.

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