embryology of respiratory system

1. Development of Respiratory System
Dr. Suresh Managutti MBBS MD Anatomy
Associate Professor
Department of Anatomy
SDM College of Medical Sciences & Hospital, Dharwad

2. As per:
Competency based Undergraduate curriculum 1
• AN25.2 Describe development of pleura, lung & heart
Medical Council of India, Competency based Undergraduate curriculum for the Indian Medical Graduate,
2018. Vol. 1; pg 1-80.

3. Formation of Lung bud
 Respiratory system develops from
- Lung bud that arises from foregut
- Connective tissue from splanchnic
mesoderm.
 During 4th week, the laryngotracheal
groove appears in floor of the pharynx.
 The laryngotracheal groove deepens to form
a laryngotracheal tube that grows caudally.
 Laryngotracheal tube bifurcates to form two
(right and left) lung buds.
 The pharyngeal cells expressing TBX4
factor forms lung buds.

4. Development of laryngotracheal or respiratory
diverticulum

6. Formation of Lung bud
 Fate of laryngotracheal tube and lung bud:
- Proximal part → forms larynx, distal part → forms the trachea.
- Lung buds → form primordium of bronchial tree and lungs.
- Splanchnic mesoderm → forms surrounding connective tissue.
 On either side of laryngotracheal tube (respiratory diverticulum), two
tracheoesophageal folds arise → fuse to form tracheoesophageal
septum → separate laryngotracheal tube form the oesophagus.
 Lung buds invaginates into the pericardioperitoneal canals that later
form pleural cavities.

7. Development of Larynx
• Q. Write short note on development of larynx.
Summary
 Components of the larynx are derived as follows:
1. Lining epithelium develops from endoderm of laryngotracheal diverticulum.
2. Vestibular and vocal folds develop from endodermal folds arising from laryngotracheal
diverticulum.
3. Cartilages of larynx: All the cartilages (thyroid, cricoid, cuneiform, arytenoids) of the larynx
develop from fourth arch, except epiglottis that develops from hypobranchial eminence.
4. Muscles of larynx: All the muscles of the larynx develop from fourth and sixth pharyngeal
arches.
5. Nerve supply is derived from the superior laryngeal nerve (fourth arch) and recurrent laryngeal
nerve (sixth arch).

9. Development of inlet of larynx – Slit, U. T shaped LT
groove

10. Development of inlet and cartilages of larynx from 4th
& 6th pharyngeal arches

11. Stages of development
 Larynx develops from cranial part of the laryngotracheal
diverticulum that arise from the floor of the pharynx.
 Communication between laryngotracheal diverticulum and pharynx
forms the inlet of larynx.
 Endoderm of larynx proliferates to block the lumen. Later the lumen
gets recanalized.
 During luminal recanalization, the endoderm form two pairs of
folding, proximal vestibular and distal vocal pair of folds.
 Vestibular fold give rise to false vocal cord and vocal fold to true
vocal cord.

12. Stages of development
 Mesenchyme of fourth and sixth arch form all the cartilages of larynx except
epiglottis that derives from hypobranchial eminence.MCQ
 All the intrinsic muscles are derived from sixth arch except cricothyroid. Hence,
all the muscles of larynx are supplied by recurrent laryngeal nerve except
cricothyroid that is supplied by external laryngeal branch of superior laryngeal
nerve.MCQ
 The recess between vestibular fold and vocal fold forms the ventricle of the
larynx.
 Mucosa above vocal fold is innervated from internal laryngeal branch of vagus
(4th arch) and below the vocal fold is innervated by recurrent laryngeal nerve (6th
arch).

13. Table 1: Development of Larynx
Part Embryological source
Mucosa Proximal part of laryngotracheal tube
Cartilages All cartilages – fourth and sixth arch except
Epiglottis – hypobranchial eminence
Intrinsic muscles All form sixth arch except cricothyroid from fourth arch.
Nerve supply Motor
All muscles by recurrent laryngeal nerve except cricothyroid by
external laryngeal branch of superior laryngeal nerve
Sensory
Above vocal folds – internal laryngeal branch of superior laryngeal
nerve
Below vocal folds – recurrent laryngeal nerve

14. Anomalies of Larynx
1. Laryngocele: It is congenital anomalous air sac in the neck communicating
with the cavity of larynx.
2. Congenital laryngeal atresia and stenosis: It results from failure of the
laryngeal recanalization (atresia is blockage and stenosis mean narrowing).
3. Laryngoptosis: Absence of some of laryngeal cartilages → Larynx is
localized in lower position.
4. Laryngeal web: Incomplete recanalization → membrane-like structure in
lumen of larynx → partial airway obstruction.

15. Development of trachea
 Trachea develops from a part of laryngotracheal tube that lies between
developing larynx and point of bifunction of tube (lung buds).
Summary
 Components of trachea develops as follows:
1. Lining epithelium and glands develop from endoderm of laryngotracheal tube.
2. Cartilages, connective tissue and trachealis muscle develop from splanchnopleuric
mesoderm surrounding laryngotracheal tube.
 Trachea is separated from oesophagus by tracheoesophageal septum that is
derived from tracheoesophageal folds.

16. Anomalies of trachea
1. Agenesis of trachea: Failure of the formation of laryngotracheal tube results
in the agenesis of the trachea.
2. Tracheoesophageal fistula
3. Tracheal stenosis: It occurs due to ventral deviation of tracheoesophageal
septum.
4. Tracheal bronchus: There may be a blind diverticulum (tracheal bronchus)
arising from the trachea.
5. Tracheal lobe: A separate bronchus may rise from trachea and supply an
isolated lobe of lung called tracheal lobe.

18. Anomalies of trachea

19. Tracheoesophageal fistula (TEF)
• Q: Write short note on trachea oesophageal fistula
 Definition: Tracheoesophageal fistula is an abnormal congenital communication between the
trachea and oesophagus.
 Incidence: 1:3000-4500 births.
 Causes: Failure of fusion of tracheoesophageal septum results in TEF.
 Types: According to morphology and anatomical locations:
– Type A: It is not true TEF. Both proximal and distal oesophageal segments do not communicate with each other or with
the trachea.
– Type B: Proximal oesophageal segment communicates with lower tracheal segment and distal oesophageal segment
form blind pouch.
– Type C: Proximal oesophageal atresia (blind pouch) and distal oesophagus arise from the trachea.
– Type D: Proximal and distal oesophageal segments communicates with the trachea.
– Type E: Oesophagus communicates with the trachea without any atresia.

20. Tracheoesophageal fistula (TEF)
 Clinical presentation
- Oesophageal atresia and subsequent inability to swallow result in
polyhydramnios.
- TEF preset with coughing, vomiting, cyanosis in new born with the
onset of feeding (entry of milk in the lungs).
 Treatment: Emergency surgical repair → surgical resection
of fistula and anastomosis of proximal and distal oesophageal
segments.

21. Development of Bronchi and lungs
 During 5th week of IUL, laryngotracheal diverticulum divides into right and left
principle bronchus (initially lung buds).
Formation of pleural cavity and pleura
 Lung buds grow in caudal and lateral direction and bulge into pleuroperitoneal
canals.
 Soon small pleuroperitoneal canals get filled with the growing lungs. Later the
canals start enlarging to accommodate the growing lungs.
 Pleuropericardial and pleuroperitoneal folds separate the pleuroperitoneal canals
from pericardial and peritoneal cavities respectively. Thus, isolated
pleuroperitoneal canal form pleural cavities.
 A layer of splanchnopleuric mesoderm in contact with lung bud form visceral
pleura and somatopleuric layer form parietal pleura.

23. Formation of intrapulmonary bronchi
 Left principle bronchus divides into upper and lower secondary or lobar bronchi,
whereas right principle bronchus divides into superior, middle and lower lobar
bronchi.
 Each secondary bronchus later supplies a lobe of lung that are separated by fissures.
 In 7th week of IUL, the secondary bronchi divide to form 10 segmental bronchi.
 Each segmental bronchus with surrounding splanchnopleuric mesoderm forms the
bronchopulmonary segments.
 The 7th month of IUL, about 17 generations of bronchial subdivisions occurs. About
6–7 divisions take place after birth before formation of adult lung.MCQ
 Distal bronchial subdivisions form bronchioles, respiratory bronchioles, alveolar
ducts and alveoli.

25. Respiratory diverticulum- growth and development

26. Parenchyma of lung
 Lining epithelium of bronchial tree and alveoli develop from endoderm of respiratory
diverticulum.
 Cartilages, blood vessels and other connective tissue elements develop from
splanchnopleuric mesoderm.
Maturation of lungs
• Q. Write short note on stages of maturation of lung.
 Maturation of lungs is divided into four phases or periods
1. Pseudo glandular period (6–16 weeks)
2. Canalicular period (16–26 weeks)
3. Terminal saccular period (26 weeks to birth) and
4. Alveolar period (32 weeks to 8 years)

28. Maturation of lungs
1. Pseudo glandular period
- Developing lung resembles an exocrine gland
- At the end of this period, all the major elements of lung up to the
terminal bronchiole are formed.
- The foetus is not viable.
2. Canalicular period
- During this stage, respiratory bronchiole, alveolar ducts and primary
alveoli are formed.
- Foetus born at the end of canalicular period can survive with intensive
care.

29. Maturation of lungs
3. Terminal sac period
- During this stage, substantial number of primary alveoli are formed.
- Blood air barrier (endothelio-epithelial barrier) thin out.
- Type II pneumocytes produce surfactant.
4. Alveolar period
- During this period, definitive alveoli develop and increases in number.
- Type II pneumocytes continue production of more surfactant.
- Formation of definitive alveoli continue after the birth up to the age of
8th years.

30. Stages of histogenesis of lung

31. Sagittal section of developing lung at 6weeks of
gestation

32. Anomalies of Lungs
1. Hyaline membrane disease
2. Agenesis and hypoplasia: The part or the complete lung
on one side may be absent or under developed.
3. Abnormal lobulation:
- Absence of fissure result in reduction of number of lobes.
- Extra fissure: It includes following cases:
 A transverse fissure in left lung
 Separate medial basal segment called cardiac lobe
 Separate superior segment of lower lobe.
4. Azygous lobe (Lobe of Wrisberg): The part of upper of lobe the right lung that lies
medial to arch of the azygous vein is called azygous lobe. A vertical fissure separates
azygous lobe from rest of the superior lobe of the lung. Azygous vein lies in the floor
of vertical fissure. Azygous lobe is commonest accessory lobe of the lung.MCQ

33. Anomalies of Lungs
1. Sequestration of the lung tissue: A separate area of embryonic lung tissue from the
tracheobranchial tree is called sequestration (means separation).
2. Ectopic lung: It occurs due to development of the additional lung bud from the oesophagus.
3. Congenital polycystic lung: The terminal bronchioles dilate to form multiple cysts and thus,
produces honey-comb appearance on radiographs.
4. Medicolegal aspect: Lungs of alive newborn (liveborn) contains air and hence float in the water,
whereas lungs of still born babies (dead born) do not contain air and hence their lungs sink in the
water. This fact can be used to differentiate between still born and killed live born baby.
5. VACTERL association have following components:MCQ
- Vertebral anomalies, Anal atresia
- Cardiac defects, Tracheoesophageal fistula
- Esophageal atresia, Renal anomalies, Limb defects
Human Embryology/Yogesh Sontakke/2nd edn/CBS Publishers

34. Hyaline Membrane Disease or Infant Respiratory Distress
Syndrome (IRDS)
• Q. Write short note on Hyaline Membrane Disease.
 It is also called as surfactant deficiency disorder.
 It is produced in premature infants due to the deficiency of the surfactant.
 Production of surfactant begins by 20th week of IUL.MCQ The amount of surfactant
increases during last two weeks before birth.
 Incidence:
- It affects about 1% of newborn infants and it is one of the leading cause of death in preterm
infants.
- Hyaline membrane disease accounts for 20% of deaths among newborns.MCQ
• Signs and symptoms
- Fast breathing
- Fast heart rate
- Blue discoloration of skin (cynosis).

35. Hyaline membrane disease or Infant
Respiratory Distress Syndrome (IRDS)
• Pathological finding
 Waxy appearing layers of hyaline membrane that line the collapsed alveoli of the lung.
• Prevention: To speed up production of surfactant, injectable glucocorticoids are given
to the mother during last trimester (after 7th month of pregnancy).
• Diagnostic amniocentesis
 Lecithin sphingomyelin (L/S) ratio in amniotic fluid: L/S ratio less than 2:1 indicates
insufficient surfactant.MCQ
 Surfactant/albumin (S/A) ratio in amniotic fluid: The S/A ratio < 35 indicates immature
lungs, 35–55 indicates intermediate maturity and > 55 indicates sufficient maturity of
lungs.
• Treatment: Newborn can be supported with oxygen therapy, continuous positive airway
pressure, exogenous surfactant is useful.

36. Development of Pleural Cavity
• Pleural cavities develop from right and left pericadio-
peritoneal canals that connects pericardial cavity with
peritoneal cavities.
• Stages of development
1. Invagination stage: Lung buds invaginates pericardio-
peritoneal canals.
2. Enlargement: Pericaridio-periotoneal canals enlarges to
accommodate enlarge lung buds.
3. Separation: Two folds of somatopleuric mesoderm appears in relation to invaginated lung buds.
- Cranial pericardio-pleural fold (membrane) separates pericardial cavity from pleural cavity.
- Caudal pleuroperitoneal fold (membrane) separates pleural cavity from peritoneal cavity.
- Both of these membranes become continuous with the posterior border of the septum transversum

37. Development of Pleural Cavity
4. Closure of pleuro pericardial opening: During sixth week, pleuropericardial
opening fuses due to the fusion of pleuro-pericardial membrane with the
mesodermal tissue surrounding oesophagus. Overgrowing lung bud turns
pleura-pericardial membrane and make it vertical (initially oblique).
5. Closure of pleuro-peritoneal opening
 Boundaries of pleura peritoneal opening are as follows:
• Ventral: dorsal border of septum transversum
• Medial: oesophagus, dorsal mesentery of oesophagus and dorsal aorta
• Dorsal: mesonephric ridge with gonads
• Lateral: pleuroperitoneal membrane.
 Pleura-peritoneal membranes grow ventrally and fuse with dorsal border of septum
transversum and other structures forming boundaries of pleuro-peritoneal openings.

38. Development of Pleural Cavity
6. Expansion of pleural cavities: expanding lung buds causes expansion of
pleural cavities in the mesoderm (causes decent of heart.) antero-posteriorly and
craniocaudally.
7. Formation of pleuro-pericardial membrane: expanding pleural cavity splits
mesoderm into two layers
a. Outer layer forms wall of thorax
b. Inner layer lines pericardial cavity. This layer is called pleuropericardial membrane and
it later forms fibrous pericardium.

39. Developing lung buds coming in contact with
pleuropericardial canal

40. 3 coelomic cavities with pleuropericardial and
pleuroperitoneal membranes

41. Invagination of lung bud into pleural cavity,formation
of pleuropericardial membrane

43. Developing larynx, trachea and lungs

44. Abnormal lobes of lungs

45. Azygous lobe of lung

46. Foetus with extra thoracic lung in abdominal cavity

47. • Thank you…………….