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Respiratory system and lung development: want to learn more about it?

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Respiratory system and lung development

The development of the respiratory system is tightly associated with the digestive system from the beginning. It is therefore not surprising that defects in the foregut region often involve the cranial level of both systems. This article will focus on the five phases of development of the lungs, as well as their expansion within the body cavity. Familiarizing yourself with this topic will give you a deeper appreciation of the intricacies tied to development of our respiratory tree.

Phases of development


The embryonic phase takes place between the third and sixth week of gestation. The development of the lungs begins during the third week, with the appearance of a respiratory diverticulum (lung bud) as an outgrowth from the ventral wall of the foregut. The lung bud expands in a ventral and caudal direction, invading the mesenchyme surrounding the foregut. Soon after, the lung bud being initially in open communication with the foregut, becomes separated from it eventually forms the esophagus.

Concurrently, the distal end of the lung bud bifurcates into the right and left primary bronchial buds, whereas the proximal end (stem) forms the trachea and larynx. By the fifth week of gestation, the primary bronchial buds form three secondary bronchial buds on the right side and two on the left, foreshadowing the primordial lobes of the lungs. Each secondary bronchial bud gives rise to ten tertiary bronchial buds on both sides, demarcating the end of the embryonic phase.


The pseudoglandular phase takes place during between the sixth and sixteenth week of gestation. The respiratory tree undergoes twelve to fourteen more generations of branching, resulting in the formation of terminal bronchioles. This passageway will be lined with a specific type of respiratory epithelium, simple columnar epithelium (ciliated) transitioning to simple cuboidal epithelium (some cilia).

Terminal bronchiole (anterior view)


The canalicular phase takes place during the sixteenth and twenty-eighth week of gestation. Each terminal bronchioles further divide into respiratory bronchioles, which become surrounded with an increase in vascularization. Subsequently, the lumens of the respiratory bronchioles become enlarged as a result of the thinning of their epithelial walls. This process sets up the differentiation of specialized cell types associated with the lungs.

Respiratory bronchiole (histological slide)


The saccular phase takes place between the twenty-eighth and thirty-sixth week of gestation. The respiratory bronchioles give rise to a final generation of terminal branches. These branches become invested in a dense network of capillaries, forming the terminal sacs (primitive alveoli) that are lined with type I and type II alveolar cells.

Type I pneumocytes (histological slide)

Type I alveolar cells (type I pneumocyte) are branched cells which are the gas exchange surface in the alveolus. Type II alveolar cells act as the ‘caretaker’ by responding to damage of the type I cells. Type II alveolar cells do this by dividing and acting as a progenitor cell for both type I and type II cells. In addition, they synthesise, store and release pulmonary surfactant into the alveolar hypophase, where it acts to optimise conditions for gas exchange. Although gas exchange is possible at this point, it is very limited as the alveoli are still immature and few in numbers. In fact, the formation of the terminal sacs continues during fetal and postnatal life. Prior to birth, there are approximately twenty million to seventy million terminal sacs, whereas the total number in a mature lung is approximately three-hundred to four-hundred million.

Type II pneumocytes (histological slide)


The alveolar phase is characterized by the maturation of the alveoli, a process that takes place during the end of fetal life and many years after birth.

Alveolus (anterior view)


During the development of the respiratory tree, the primordial lungs expand into the pericardioperitoneal canals of the body cavity. At this stage, these canals are in open communication with the peritoneal and pericardial cavities; they lie on each side of the foregut and are gradually filled by the expanding lungs.

Soon after, the pleuroperitoneal and pleuropericardial folds separate the pericardioperitoneal canals from the peritoneal and pericardial cavities, respectively. This results in the formation of the pleural cavity. The visceral pleura derives from the mesoderm that lines the outside of the lungs, whereas the parietal pleura derives from the somatic mesoderm that lines the body wall.

Pleural cavity (lateral-right view)

Note that because the lung bud is an outgrowth of the foregut, the lungs are composed of endodermal and mesodermal tissues. The endoderm gives rise to the mucosal lining of the bronchi and the epithelial cells of the alveoli. The mesoderm (middle layer of an embryo) helps give rise to the remaining components of the lungs. Specifically, the splanchnopleuric mesoderm, gives rise to: the vasculature, connective tissue, muscle, and cartilage associated with the bronchi, and the pleura of the lungs.

Left lung (medial view)

Clinical aspects

Defective portioning of the esophagus and the trachea can result in esophageal atresia and tracheoesophageal fistula. Esophageal atresia (EA) is characterized by a blind-ended closure of either the proximal part, distal part, or both parts of the esophagus. Tracheoesophageal fistula (TEF) is characterized by an abnormal connection between the tracheal and esophageal lumens. EA and TEF usually accompany each other. However, many variations of these defects exist, including a proximal EA with or without a distal TEF, an isolated TEF without any EA, or an isolated EA without any TEF.

Esophageal atresia and tracheoesophageal fistula are often associated with other birth defects, including cardiac abnormalities. This is known as the VACTERL association (Vertebral anomalies, Anal atresia, Cardiac defects, Tracheoesophageal fistula, Esophageal fistula, Renal anomalies, and Limb defects). Alone, both esophageal atresia and tracheoesophageal fistula can prevent the fetus from swallowing amniotic fluid. Instead of being returned to the mother via placental circulation, there is an excess of amniotic fluid (polyhydramnios) that results in the distention of the uterus. In newborns, these defects can also be dangerous because they allow milk or other fluids to be directly aspirated into the lungs, causing pneumonitis and pneumonia. Therefore, this is often surgically corrected after birth. The clinical reference of this phase has to do with premature birth and Respiratory distress syndrome (RDS) which is the most common lung problem in a premature baby. A baby develops RDS when the lungs do not produce sufficient amounts of surfactant. This is a substance that keeps the tiny air sacs in the lung open

Respiratory system and lung development: want to learn more about it?

Our engaging videos, interactive quizzes, in-depth articles and HD atlas are here to get you top results faster.

What do you prefer to learn with?

“I would honestly say that Kenhub cut my study time in half.” – Read more. Kim Bengochea Kim Bengochea, Regis University, Denver

Show references


  • G.C. Schoenwolf, S.B. Bleyl, P.R. Braeur & P.H. Francis-West: Larsen’s Human Embryology, 5th edition, Churchill Livingstone (2015), p. 172-196, 501-523
  • K.L. Moore, T.V.N. Persaud & M.G. Torchia: The Developing Human: Clinically Oriented Embryology, 10th edition, Elsevier (2016), p. 355-378
  • T.W. Sadler: Langman’s Medical Embryology, 12th edition, Wolters Kluwer, Lippincott Williams & Wilkins (2012), p. 133-161


  • Terminal bronchiole (anterior view) - Paul Kim
  • Respiratory bronchiole (histological slide) - Smart In Media
  • Type I pneumocytes (histological slide) - Smart In Media
  • Type II pneumocytes (histological slide) - Smart In Media
  • Alveolus (anterior view) - Paul Kim
  • Pleural cavity (lateral-right view) - Paul Kim
  • Left lung (medial view) - Yousun Koh
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