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Development of the 
Respiratory System
FORMATION OF THE LUNG BUDS 
• Embryo is 4 weeks old 
• respiratory diverticulum (lung bud) appears as an 
outgrowth from the ventral wall of the foregut . 
• Dependent upon: retinoic acid (RA) produced by 
adjacent mesoderm. 
• Epithelium of the internal lining of the larynx, 
trachea; bronchi; lungs, is Endoderm 
• The cartilaginous; muscular,; connective tissue 
components of the trachea; lungs are splanchnic 
mesoderm ( that surrounds the foregut)
A.Embryo of approximately 25 days' gestation showing 
the relation of the respiratory diverticulum to the 
heart, stomach, and liver. 
B. Sagittal section through the cephalic end of a 5-week 
embryo showing the openings of the pharyngeal 
pouches and the laryngotracheal orifice.
FORMATION OF THE LUNG BUDS -2 
• The diverticulum expands caudally, and two 
longitudinal ridges, the tracheoesophageal 
ridges, separate it from the foregut. 
• These ridges fuse to form the tracheoesophageal 
septum 
• The respiratory primordium communicates with 
the pharynx through the laryngeal orifice 
• Foregut Divides into: 
1) Dorsal portion: Oesophagus. 
2) Ventral portion: Trachea & Lung Buds.
• A-C. Successive stages in development of the 
respiratory diverticulum showing the 
tracheoesophageal ridges and formation of the septum, 
splitting the foregut into esophagus and trachea with 
lung buds. 
• D. The ventral portion of the pharynx seen from above 
showing the laryngeal orifice and surrounding swelling.
TRACHEOESOPHAGEAL FISTULAS 
(TEFS) 
• Abnormalities in partitioning of the esophagus 
and trachea by the tracheoesophageal septum 
ensuing Esophageal Atresia with or w/o TEFs. 
• Approx. 1/3,000 births 
• Blind pouch and the lower segment forming a 
fistula with the trachea (90% of cases) 
• Isolated Oesophageal Atresia 
• H-type TEF without oesophageal Atresia
• A. most frequent 
abnormality (90% of 
cases) occurs with 
the upper 
oesophagus ending 
in a blind pouch and 
the lower segment 
forming a fistula 
with the trachea. 
• B. Isolated 
oesophageal atresia 
(4% of cases). 
• C. H-type 
tracheoesophageal 
fistula (4% of cases). 
• D,E. Other 
variations (each 1% 
of cases).
BUT THESE ABNORMALITIES ARE 
ASSOCIATED WITH OTHER BIRTH DEFECTS 
• Including cardiac abnormalities (33% of cases) 
• TEFs are a component of the VACTERL Group: 
• Vertebral anomalies 
• Anal Atresia 
• Cardiac Defects 
• Tracheoesophageal Fistula 
• Esophageal Atresia, 
• Renal Anomalies 
• Limb Defects
• A, Tracheoesophageal fistula (TEF) in a 17-week male fetus. The upper 
esophageal segment ends blindly (pointer). 
• B, Contrast radiograph of a newborn infant with TEF. Note the 
communication (arrow) between the esophagus (E) and trachea (T).
LARYNX 
• Internal lining: originates from endoderm. 
• Cartilages; muscles originate from mesenchyme 
of the 4th & 6th pharyngeal arches. 
• Laryngeal orifice changes from a sagittal slit to a 
T-shaped opening. 
• Caracteristic adult shape of the laryngeal orifice 
can be recognized when mesenchyme of the two 
arches transforms into the thyroid; cricoid; 
arytenoid cartilages.
• Laryngeal orifice and surrounding swellings at 
successive stages of development: 
• A. 6 weeks. 
• B. 12 weeks
TRACHEA & BRONCHI & LUNGS 
• The bronchial buds forms 
• 5th week, each of these buds enlarges to form 
right and left main bronchi. 
• The right forms three secondary bronchi. 
• The left forms two.
• Stages in development of the trachea and lungs: 
• A. 5 weeks. 
• B. 6 weeks. 
• C. 8 weeks
Further Development 
• Subsequent growth in caudal and lateral 
directions, the lung buds expand into the body 
cavity . 
• The spaces for the lungs, which are the 
pericardioperitoneal canals, are narrow. 
• The mesoderm[covers outside of the lung] 
develops into the visceral pleura. 
• The somatic mesoderm layer[covering the body 
wall from the inside] becomes the parietal pleura 
• The space between the parietal and visceral 
pleura is the pleural cavity .
• Expansion of the lung buds into the pericardioperitoneal 
canals. At this stage, the canals are in communication with 
the peritoneal and pericardial cavities. 
• A. Ventral view of lung buds. 
• B. Transverse section through the lung buds showing the 
pleuropericardial folds that will divide the thoracic portion of 
the body cavity into the pleural and pericardial cavities.
• pericardioperitoneal 
canals separate from 
the pericardial and 
peritoneal cavities, 
• the lungs expand in 
the pleural cavities. 
• Note the visceral and 
parietal pleura and 
definitive pleural 
cavity. The visceral 
pleura extends 
between the lobes of 
the lungs.
Further development 
• Secondary bronchi divide repeatedly in a dichotomous 
fashion forming tertiary (segmental) bronchi. 
• Right lung: forming ten. 
• Left: forming eight. 
• Creating the bronchopulmonary segments of the adult 
lung. 
• By the end of the sixth month, approximately 17 
generations of subdivisions have formed. Before the 
bronchial tree reaches its final shape. 
• But, an additional six divisions form during postnatal life. 
• For Maturation of the lungs, check your book pg: 205
Surfactant 
• Important for survival of the premature infant. 
• When insufficient, the air-water (blood) 
surface membrane tension becomes high, 
bringing great risk that alveoli will collapse 
during expiration. 
• Resulting in respiratory distress syndrome 
(RDS) 
• Common cause of death in the premature 
infant.
SUMMARY 
• The respiratory system is an outgrowth of the ventral wall of the foregut 
• Epithelium of the larynx; trachea; bronchi; alveoli originates is endoderm. 
• The cartilaginous; muscular; connective tissue components arise from 
mesoderm. 
• In the fourth week of development, the tracheoesophageal septum 
separates the trachea from the foregut 
• Dividing the foregut into the lung bud anteriorly & esophagus posteriorly. 
• Contact between the two is maintained through the larynx, which is 
formed by tissue of the fourth and sixth pharyngeal arches. 
• The lung bud develops into two main bronchi: 
• the right forms three secondary bronchi and three lobes; 
• the left forms two secondary bronchi and two lobes. 
• Faulty partitioning of the foregut by the tracheoesophageal septum 
causes oesophageal atresias and tracheoesophageal fistulas
Quiz - 1 
• Q: A prenatal ultrasound revealed polyhydramnios, and at 
birth, the baby had excessive fluids in its mouth. What type of 
birth defect might be present, and what is its embryological 
origin? Would you examine the child carefully for other birth 
defects? Why? 
• A: This infant most likely has some type of tracheoesophageal atresia with 
or without a tracheoesophageal fistula. 
• The baby cannot swallow, and this condition results in polyhydramnios. 
• The defect is caused by abnormal partitioning of the trachea and 
oesophagus by the tracheoesophageal septum. 
• These defects are often associated with other malformations, including a 
constellation of vertebral anomalies, anal atresia, cardiac defects, renal 
anomalies, and limb defects known as the VACTERL association
Quiz - 2 
• A baby born at 6 months' gestation is having 
trouble breathing. Why? 
• Babies born before 7 months of gestation do not produce 
sufficient amounts of surfactant to reduce surface tension in 
the alveoli to permit normal lung function. 
• Consequently, alveoli collapse, resulting in respiratory 
distress syndrome. Recent improvements in artificial 
surfactants have improved the prognosis for these infants
THE END

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Development of the Respiratory System from Lung Buds to Alveoli

  • 1. Development of the Respiratory System
  • 2. FORMATION OF THE LUNG BUDS • Embryo is 4 weeks old • respiratory diverticulum (lung bud) appears as an outgrowth from the ventral wall of the foregut . • Dependent upon: retinoic acid (RA) produced by adjacent mesoderm. • Epithelium of the internal lining of the larynx, trachea; bronchi; lungs, is Endoderm • The cartilaginous; muscular,; connective tissue components of the trachea; lungs are splanchnic mesoderm ( that surrounds the foregut)
  • 3. A.Embryo of approximately 25 days' gestation showing the relation of the respiratory diverticulum to the heart, stomach, and liver. B. Sagittal section through the cephalic end of a 5-week embryo showing the openings of the pharyngeal pouches and the laryngotracheal orifice.
  • 4. FORMATION OF THE LUNG BUDS -2 • The diverticulum expands caudally, and two longitudinal ridges, the tracheoesophageal ridges, separate it from the foregut. • These ridges fuse to form the tracheoesophageal septum • The respiratory primordium communicates with the pharynx through the laryngeal orifice • Foregut Divides into: 1) Dorsal portion: Oesophagus. 2) Ventral portion: Trachea & Lung Buds.
  • 5. • A-C. Successive stages in development of the respiratory diverticulum showing the tracheoesophageal ridges and formation of the septum, splitting the foregut into esophagus and trachea with lung buds. • D. The ventral portion of the pharynx seen from above showing the laryngeal orifice and surrounding swelling.
  • 6. TRACHEOESOPHAGEAL FISTULAS (TEFS) • Abnormalities in partitioning of the esophagus and trachea by the tracheoesophageal septum ensuing Esophageal Atresia with or w/o TEFs. • Approx. 1/3,000 births • Blind pouch and the lower segment forming a fistula with the trachea (90% of cases) • Isolated Oesophageal Atresia • H-type TEF without oesophageal Atresia
  • 7. • A. most frequent abnormality (90% of cases) occurs with the upper oesophagus ending in a blind pouch and the lower segment forming a fistula with the trachea. • B. Isolated oesophageal atresia (4% of cases). • C. H-type tracheoesophageal fistula (4% of cases). • D,E. Other variations (each 1% of cases).
  • 8. BUT THESE ABNORMALITIES ARE ASSOCIATED WITH OTHER BIRTH DEFECTS • Including cardiac abnormalities (33% of cases) • TEFs are a component of the VACTERL Group: • Vertebral anomalies • Anal Atresia • Cardiac Defects • Tracheoesophageal Fistula • Esophageal Atresia, • Renal Anomalies • Limb Defects
  • 9. • A, Tracheoesophageal fistula (TEF) in a 17-week male fetus. The upper esophageal segment ends blindly (pointer). • B, Contrast radiograph of a newborn infant with TEF. Note the communication (arrow) between the esophagus (E) and trachea (T).
  • 10. LARYNX • Internal lining: originates from endoderm. • Cartilages; muscles originate from mesenchyme of the 4th & 6th pharyngeal arches. • Laryngeal orifice changes from a sagittal slit to a T-shaped opening. • Caracteristic adult shape of the laryngeal orifice can be recognized when mesenchyme of the two arches transforms into the thyroid; cricoid; arytenoid cartilages.
  • 11. • Laryngeal orifice and surrounding swellings at successive stages of development: • A. 6 weeks. • B. 12 weeks
  • 12. TRACHEA & BRONCHI & LUNGS • The bronchial buds forms • 5th week, each of these buds enlarges to form right and left main bronchi. • The right forms three secondary bronchi. • The left forms two.
  • 13. • Stages in development of the trachea and lungs: • A. 5 weeks. • B. 6 weeks. • C. 8 weeks
  • 14. Further Development • Subsequent growth in caudal and lateral directions, the lung buds expand into the body cavity . • The spaces for the lungs, which are the pericardioperitoneal canals, are narrow. • The mesoderm[covers outside of the lung] develops into the visceral pleura. • The somatic mesoderm layer[covering the body wall from the inside] becomes the parietal pleura • The space between the parietal and visceral pleura is the pleural cavity .
  • 15. • Expansion of the lung buds into the pericardioperitoneal canals. At this stage, the canals are in communication with the peritoneal and pericardial cavities. • A. Ventral view of lung buds. • B. Transverse section through the lung buds showing the pleuropericardial folds that will divide the thoracic portion of the body cavity into the pleural and pericardial cavities.
  • 16. • pericardioperitoneal canals separate from the pericardial and peritoneal cavities, • the lungs expand in the pleural cavities. • Note the visceral and parietal pleura and definitive pleural cavity. The visceral pleura extends between the lobes of the lungs.
  • 17. Further development • Secondary bronchi divide repeatedly in a dichotomous fashion forming tertiary (segmental) bronchi. • Right lung: forming ten. • Left: forming eight. • Creating the bronchopulmonary segments of the adult lung. • By the end of the sixth month, approximately 17 generations of subdivisions have formed. Before the bronchial tree reaches its final shape. • But, an additional six divisions form during postnatal life. • For Maturation of the lungs, check your book pg: 205
  • 18. Surfactant • Important for survival of the premature infant. • When insufficient, the air-water (blood) surface membrane tension becomes high, bringing great risk that alveoli will collapse during expiration. • Resulting in respiratory distress syndrome (RDS) • Common cause of death in the premature infant.
  • 19. SUMMARY • The respiratory system is an outgrowth of the ventral wall of the foregut • Epithelium of the larynx; trachea; bronchi; alveoli originates is endoderm. • The cartilaginous; muscular; connective tissue components arise from mesoderm. • In the fourth week of development, the tracheoesophageal septum separates the trachea from the foregut • Dividing the foregut into the lung bud anteriorly & esophagus posteriorly. • Contact between the two is maintained through the larynx, which is formed by tissue of the fourth and sixth pharyngeal arches. • The lung bud develops into two main bronchi: • the right forms three secondary bronchi and three lobes; • the left forms two secondary bronchi and two lobes. • Faulty partitioning of the foregut by the tracheoesophageal septum causes oesophageal atresias and tracheoesophageal fistulas
  • 20. Quiz - 1 • Q: A prenatal ultrasound revealed polyhydramnios, and at birth, the baby had excessive fluids in its mouth. What type of birth defect might be present, and what is its embryological origin? Would you examine the child carefully for other birth defects? Why? • A: This infant most likely has some type of tracheoesophageal atresia with or without a tracheoesophageal fistula. • The baby cannot swallow, and this condition results in polyhydramnios. • The defect is caused by abnormal partitioning of the trachea and oesophagus by the tracheoesophageal septum. • These defects are often associated with other malformations, including a constellation of vertebral anomalies, anal atresia, cardiac defects, renal anomalies, and limb defects known as the VACTERL association
  • 21. Quiz - 2 • A baby born at 6 months' gestation is having trouble breathing. Why? • Babies born before 7 months of gestation do not produce sufficient amounts of surfactant to reduce surface tension in the alveoli to permit normal lung function. • Consequently, alveoli collapse, resulting in respiratory distress syndrome. Recent improvements in artificial surfactants have improved the prognosis for these infants

Editor's Notes

  1. Splanchnic: Relating to or affecting the viscera.
  2. Primordioum: An organ in its earliest stage of development; the foundation for subsequent development.
  3. Fistula: An abnormal passage leading from a suppurating cavity to the body surface. Atresia: An abnormal condition in which a normal opening or tube in the body (as the urethra) is closed or absent.
  4. A complication of some TEFs is polyhydramnios, since in some types of TEF, amniotic fluid does not pass to the stomach and intestines. Also, gastric contents and/or amniotic fluid at birth may enter the trachea through a fistula, causing pneumonitis and pneumonia
  5. Laryngeal orifice changes shape result of rapid growth of mesenchyme. Thyroid: A gland located near the base of the neck. Arytenoid cartilages: Either of two small cartilages at the back of the larynx to which the vocal folds are attached. The cricoid cartilage: A complete ring cartilage around the trachea.
  6. Branching is regulated by epithelial-mesenchymal interactions between the endoderm of the lung buds and splanchnic mesoderm that surrounds them. Signals for branching, which emit from the mesoderm, involve members of the fibroblast growth factor family. While all of these new subdivisions are occurring and the bronchial tree is developing, the lungs assume a more caudal position, so that by the time of birth, the bifurcation of the trachea is opposite the fourth thoracic vertebra.