The development of the lungs is a complex biological process that begins early in gestation, preparing the fetus for its first breath. This system must evolve from a simple tissue bud into a complex network of airways and blood vessels capable of efficient gas exchange. Although the lungs are not functionally necessary while a fetus is sustained by the placenta, their structural and functional maturity at birth is the primary determinant of survival outside the womb. This developmental journey involves a precise sequence of anatomical changes, culminating in a fully mature organ system years after birth.
The Five Stages of Lung Development
The formation of the human lung follows a predictable chronological sequence divided into five distinct stages. The Embryonic Stage (3 to 5 weeks) is when the respiratory system originates as an outgrowth, known as the lung bud, from the foregut. This initial bud quickly divides, establishing the beginnings of the left and right main bronchi.
The Pseudoglandular Stage (5 to 16 weeks) is characterized by extensive branching of the airways. During this time, the entire conducting portion of the respiratory tree, from the bronchi down to the terminal bronchioles, is formed.
The Canalicular Stage (16 to 26 weeks) is marked by the ‘canalization’ of the lung tissue. Terminal bronchioles divide into respiratory bronchioles, and the earliest air sacs, called saccules, begin to form. During this phase, the connective tissue becomes highly vascularized, bringing developing capillaries closer to the airspaces. This thinning allows the first appearance of the blood-air barrier, which is required for gas exchange.
The Saccular Stage (24 weeks until term) involves the expansion of the lung’s gas-exchange surface area as the saccules become larger and increase in number. The final stage is the Alveolar Stage, which begins around 36 weeks gestation and continues well into childhood. This phase involves the maturation of primitive saccules into true, thin-walled alveoli, multiplying the respiratory surface area.
The Role of Surfactant and Alveoli
The mechanical success of breathing relies on the formation of the alveoli and the presence of a specific biochemical agent. Alveoli are the delicate, balloon-like terminal air sacs of the lung, serving as the primary sites where oxygen enters the bloodstream and carbon dioxide is removed. Their thin walls are lined by two types of cells: Type I pneumocytes, which facilitate gas exchange, and Type II pneumocytes, which produce pulmonary surfactant.
Surfactant is a complex lipoprotein substance, composed primarily of lipids and proteins. Its main function is to reduce the surface tension at the air-liquid interface within the alveoli. Without this reduction in tension, the small air sacs would collapse completely upon exhalation, making it difficult to re-inflate them with the next breath.
The continuous film of surfactant stabilizes the alveoli, preventing collapse and ensuring that the work of breathing is manageable. Surfactant production by Type II cells typically begins around 24 weeks of gestation, but sufficient quantities for independent breathing are usually not available until closer to term. This functional component defines a mechanically mature lung, ready for life outside the fluid-filled environment of the womb.
Viability and Respiratory Distress in Premature Infants
The timeline of lung development directly determines the viability of a fetus born prematurely, as survival is closely linked to the structural maturity of the respiratory system. The earliest point of potential viability coincides with the Canalicular Stage, around 24 to 26 weeks, when the first primitive air-blood barrier is established and Type II cells begin to produce minimal amounts of surfactant. Infants born before this stage, during the Pseudoglandular phase, lack the necessary terminal airspaces and vasculature for gas exchange and are generally unable to survive.
A major complication for premature infants is Respiratory Distress Syndrome (RDS), which occurs due to insufficient production of pulmonary surfactant and the structural immaturity of the lungs. The lack of surfactant causes the delicate alveoli to collapse with each breath, leading to increased breathing effort, rapid breathing, and a dangerous buildup of carbon dioxide. RDS is particularly common in babies born before 28 weeks of gestation, as their lungs are still in the Saccular stage with only primitive air sacs.
To prepare for an anticipated premature birth, expectant mothers may receive antenatal steroids, such as betamethasone. These steroid injections accelerate the maturation of the fetal lungs by promoting the differentiation of Type II pneumocytes and stimulating surfactant production. Once born, infants with RDS often require supportive care, including mechanical ventilation to assist breathing and the direct administration of artificial or animal-derived surfactant into the lungs.
Lung Development After Birth
While the lungs are sufficiently developed at term to support life, maturation continues after birth through a period of rapid growth and refinement. At birth, the lungs have only a fraction of the total number of alveoli found in an adult lung. The transition to air breathing triggers a significant increase in the rate of alveolar formation, a process known as alveolarization.
This phase of postnatal lung development continues rapidly throughout the first two to three years of life. During this time, the number of alveoli multiplies, increasing the surface area available for gas exchange. Although the most intense period of growth is in early childhood, alveolarization and the maturation of the pulmonary microvasculature can continue until a child is approximately eight years old, with some evidence suggesting it may extend into young adulthood.