Development of respiratory system

ANATOMY

1. DEVELOPMENT OF RESPIRATORY SYSTEM Introduction RS has differents parts like nose , nasopharynx & oropharynx, larynx, trachea, bronchi &lungs). Here we will discuss from larynx to lungs. RS develops from Respiratory diverticulum (LUNG BUD), which appears as an outgrowth from the ventral wall of the primitive foregut,at 4 th week of intrauterine life.

2. primitive foregut

3. IMPORTANT POINTS ( for spotter) Respiratory system is ENDODERMAL in origin. RS develops from RESPIRATORY DIVERTICULUM > ( LUNG BUD ) . Lungs develop from Lung bud. RS develops at 4 th week of IUL. Factors responsible for development of RS are 1> Retinoic acid –produced by adjacent mesoderm 2> Transcription factor TBX4 – present in endoderm of GUT TUBE (GIT) LINING EPITHELIUM of LARYNX,TRACHEA ,BRONCHI & LUNG is derived from ENDODERM CARTILAGES,MUSCLES & CONNECTIVE TISSUE OF RS is derived from SPLANCHNIC MESODERM surrounding the foregut.

4. FORMATION OF LUNG BUD / RESPIRATORY DIVERTICULUM / LARYNGOTRACHEAL DIVERTICULUM This diverticulum is 1 st seen as a midline groove called Laryngotracheal groove in the endodermal lining of primitive pharynx just caudal to hypobronchial eminence during 4 th week of IUL. The groove deepens to form a longitudinal diverticulum called Laryngotracheal diverticulum which is in open communication with the foregut. As the LD expand caudally, two longitudinal ridge/fold called Tracheoesophageal ridge develop that grow medially & fuse to form septum called Tracheoesophageal septum , which separates the distal part of LD from foregut ( esophagus ).whereas the cranial part continues to communicate with pharynx. This communication with pharynx forms Laryngeal inlet . The separated part of LD grows downwards to enter thorax & form TRACHEA & Rt.& Lt. BRONCHIAL BUD . The cranial most part of LD gives development of LARYNX. Each bronchial bud invaginates into Pericardioperitoneal canal .This canal forms the pleural cavities .

5. FORMATION OF LUNG BUD/RESPIRATORY DIVERTICULUM/LARYNGOTRACHEAL DIVERTICULUM a midline groove called Laryngotracheal groove The groove deepens to form a longitudinal diverticulum ( Laryngotracheal diverticulum ) / [LD] Which is in open communication with the foregut. Tracheoesophageal ridge develop from side form septum called Tracheoesophageal septum , which separates the distal part of LD from foregut ( esophagus ). But communicates with pharynx through Laryngeal inlet . The separated part of LD grows downwards to enter thorax & form TRACHEA & Rt.& Lt. BRONCHIAL BUD . The cranial most part of LD gives development of LARYNX.

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7. Introduction RS is divided into URT ( nose,nasopharynx & oropharynx ) and LRT ( larynx,trachea,bronchi &lungs). Here we will discuss about LRT. RS develops from Respiratory diverticulum (LUNG BUD), which appears as an outgrowth from the ventral wall of the primitive foregut,at 4 th week of intrauterine life. DEVELOPMENT OF LARYNX & REVIEW OF FORMATION OF RESPIRATORY DIVERTICULUM // LARYNGO-TRACHEAL DIVERTICULUM

8. . The larynx develops from the cranial most part of the Laryngotracheal diverticulum . The communication between the laryngotracheal diverticulum & primitive pharynx persists as Laryngeal inlet . The internal lining of larynx originates from Endoderm, & all the cartilages (except Epiglottis) & muscles originates from 4 th & 6 th pharyngeal arches. The epiglottis develop from the caudal part of Hypobronchial eminence. Since vagus is the nerve of 4 th & 6 th pharyngeal arch. Hence superior laryngeal nerve innervates derivatives of 4 th pharyngeal arch, Recurrent Laryngeal nerve innervates derivatives of 6 th pharyngeal arch. During development, proliferation of mesenchyme form cartilages like thyroid,cricoid,arytenoid , & laryngeal inlet become T-shaped ,on the other hand , rapid proliferation of endodermal cells (of lining epithelium) obliterate the lumen of larynx temporarily . Later on the cells obliterating the lumen breakdown and recanalization of larynx takes place .during recanalization , the endodermal cells form two pair of folds ,which extends antero-posteriorly in the lumen of larynx , the upper pair is vestibular fold and lower pair is vocal fold and give rise to False & True vocal cord respectively. A pair of lateral recesses bounded by these folds is called Laryngeal ventricles .

9. Nerve supply of larynx All intrinsic muscles of larynx except cricothyroid is supplied by recurrent laryngeal while cricothyroid by external laryngeal nerve. Sensory supply- internal laryngeal nerve supplies the mucous membrane above the true vocal cord and Recurrent laryngeal nerve supplies mucosa below the level the vocal cord.

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11. DEVELOPMENT OF LARYNX & REVIEW OF FORMATION OF RESPIRATORY DIVERTICULUM // LARYNGO-TRACHEAL DIVERTICULUM .

12. LARYNGO-TRACHEAL GROOVE IN PRIMITIVE FOREGUT(caudal part of pharynx),Distal to hypobronchial eminence . LARYNGOTRACHEAL DIVERTICULUM ( LD) (communicating with primitive foregut) TRACHEO-ESOPHAGEAL RIDGE / FOLD TRACHEO-ESOPHAGEAL SEPTUM SEPARATION OF “LD” DISTAL PART OF LD GET SEPARATED FROM PRIMITIVE FOREGUT (ESOPHAGUS), BUT CRANIAL PART REMAINS IN CONTINUITY WITH FOREGUT (CAUDAL PART OF PHARYNX) THIS CONTINUITY FORMS LARYNGEAL INLET (SLIT LIKE ) & CRANIAL PART OF “ LD” FORMS LARYNX. i.e. Larynx develop from cranial most part of the laryngo -tracheal diverticulum (lung Bud)

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14. DEVELOPMENT OF LARYNX

15. LARYNX Cartilage & muscle of larynx ,originate from mesenchyme of 4 th &6 th pharyngeal arches Mesenchyme proliferate rapidly & form laryngeal cartilages like- thyroid,cricoid&arytenoid and these cartilages change the shape of laryngeal inlet from slit like to T-shaped . * EPIGLOTTIS develop from caudal part of Hypobronchial eminence. NERVE SUPPLY OF LARYNX-by nerve of 4 th & 6 th Ph.Arches – vagus . 1> superior laryngeal nerve supply derivatives of 4 th ph. Arch 2> Recurrent laryngeal nerve innervates derivative of 6 th ph. Arch. Internal lining of Larynx Originates from Endoderm This lining epithelium proliferates rapidly & temporarily close the lumen of the Larynx. Then vacuolization & recanalization occur As a result a pair of lateral recesses (space) formed, called Laryngeal ventricle . These recesses are bounded by folds of tissue called Vestibular fold & vocal fold , that form false and true vocal cord respectively.

16. APPLIED RELATED TO DEVELOPMENT OF LARYNX 1>Laryngeal atresia & stenosis - d/t failure of recanalization of larynx , leading to obstruction of URT.it is also called congenital high airway obstruction syndrome. 2>Laryngeal web- an abnormal membranous ,web like tissue is present in the lumen of larynx , near the vocal fold. This also partially obstruct the airway. 3>One or more laryngeal cartilage may be absent . 4> MAY BE DOUBLE LARYNX OR SOME PART OF IT MAY BE DOUBLE 5>LARYNGOPTOSIS - the larynx lies at lower level , it may lies behind the sternum. 6>LARYNCOELE- In this condition the laryngeal saccule (ventricles) is abnormally large & forms swelling in the neck.

17. APPLIED RELATED TO DEVELOPMENT OF LARYNX 1>Laryngeal atresia & stenosis - d/t failure of recanalization of larynx , leading to obstruction of URT.it is also called congenital high airway obstruction syndrome. 2>Laryngeal web- an abnormal membranous ,web like tissue is present in the lumen of larynx , near the vocal fold. This also partially obstruct the airway. This web like tissue is derived from endodermal cells that fail to break out during recanalization . 3>One or more laryngeal cartilage may be absent . 4> MAY BE DOUBLE LARYNX OR SOME PART OF IT MAY BE DOUBLE 5>LARYNGOPTOSIS - the larynx lies low down in the neck,some part of it may lies behind the sternum. 6>LARYNCOELE- In this condition the laryngeal saccule (ventricles) is abnormally large and may extend beyond the larynx proper & forms swelling in the neck.

18. DEVELOPMENT OF TRACHEA The trachea develops from the part of Laryngotracheal diverticulum (respiratory diverticulum ), which lies between the Larynx and point of division of LTdiv . Into Bronchial buds. Lining epithelium derived from Endoderm . Cartilage,muscle and connective tissue of trachea splanchno-pleuric mesoderm surrounding laryngotracheal groove.

19. APPLIED RELATED TO DEVELOPMENT OF TRACHEA TRACHEOESOPHAGEAL FISTULA (TEF)- abnormal communication between trachea and esophagus Tracheal stenosis or narrowing of trachea Tracheal atresia or tracheal obstruction Tracheal bronchus and tracheal lobe- sometimes trachea presents a diverticulum that may end blindly or may bear a lobe.

20. TRACHEOESOPHAGEAL FISTULA It is abnormal communication between trachea & esophagus . It is usually associated with esophageal atresia (obstruction) It is due to defective development of tracheoesophageal septum TYPES 1> upper end of esophagus ends in a blind pouch and lower part communicates with trachea (most common type of TEF, 90%) 2> H-shaped TEF- both upper & lower part of the esophagus communicate with trachea by a narrow canal near bifurcation of trachea,making a shape of “H” 3> upper part of esophagus communicates with trachea and lower end forms a blind pouch 4> both upper and lower part of esophagus communicate with trachea separately. C/F- if milk or fluid is given to newborn with TEF ,there will be coughing & choking ,d/t entery of milk in respiratory tract. May lead to lung infection or pneumonia. Complication of TEF is POLYHYDRAMINOS because in some type of TEF amniotic fluid does not pass to the stomach& intestine of fetus . TEFs are a component of VACTERL association- -- Vertebralanomalies,Anal atresia,Cardiac defects,Tracheoesophageal fistula,Esophageal atresia , Renal anomalies ,and Limb defect.

21. QUESTION A prenatal USG revealed polyhydraminos , 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? [ 4 marks] ANS- TEF with esophageal atresia / tracheoesophageal atresia with or without TEF Due to defective tracheoesophageal septum Examine for other anomalies of VACTERL association, because tracheoesophageal atresia is a component of VACTERL association.

22. DEVELOPMENT OF BRONCHUS AND LUNG The respiratory diverticulum divides into two bronchial buds . Each bronchial bud develops into a principal bronchus i.e.Lt . & Rt . Primary/principal bronchus formed. The principal bronchi divide to form secondary bronchi ,three sec. Bronchi on Rt. Side & two sec. Bronchi on Lt. Side is formed (hence 3 lobes present in Rt.lung & 2 lobes in Lt.lung ) . During further development secondary bronchi divide repeatedly in dichotomous fashion , forming 10 tertiary (segmental) bronchi in each lung (hence 10 bronchopulmonary segments present in each lung) By the end of 6 th month 17 generations of subdivision occur in bronchial tree. Nearly 6 subdivision occur in post natal life to reach the final shape of bronchial tree.. Thus division & subdivisions of each segmental bronchus form the distal part of bronchial tree consisting of Bronchioles,respiratory bronchioles,alveolar duct & Alveoli. Alveoli is foemed by expansion of the terminal part of the bronchial tree. THUS— a) LUNGS PARENCHYMA derive from BRONHIAL TREE by several subdivision of lobar bronchus. b) cartilages,smooth muscles ,& connective tissue is derived from splanchnic mesoderm c) Lining epithelium of bronchial tree is endoderm of respiratory diverticulum . LUNG BUD arise from foregut & as it grow ,it invaginates PERICARDIO-PERITONEAL CANAL . In course of development ,lung bud form LUNG & pericardio-peritonial canal form PLEURAL CAVITY after separating from pericardial & peritoneal cavity. Since pleura lines the surface of each lobe separately, the lobes become separated by fissures.

23. Development of bronchus RESPIRATORY DIVERTICULUM Right bronchial bud Rt. Principal bronchus/primary bronchus Three secondary/ lobar bronchus Ten tertiary bronchus /segmental bronchus 17 generation of subdivisions before birth & 6 subdivisions after birth Terminal bronchiole ,respiratory bronchiole,alveolar duct ,atria,, & alveoli are formed Alveoli is formed by expansion of terminal part of bronchial tree Left bronchial bud Left principal bronchus/primary bronchus Two secondary /lobar bronchus Ten tertiary/ segmental bronchus 17 genertion of subdivisions..........similar to rt. lung

24. Development of lung Lung Parenchyma – derived from bronchial tree Lining epithelium – from endoderm of resp.diverticulum Cartilages,muscle ,& connective tissue – from splanchnic mesoderm

25. APPLIED 1> Agenesis of lung 2> hypoplasia of lung 3> ectopic lung 4> abnormal lobes of lung – 2 in rt. & 3 in left, due to abnormal division of principal bronchus 5> congenital polycystic lung 6> azygos lobe of lung

26. APPLIED RELATED TO DEVELOPMENT OF BRONCHUS & LUNG 1> agenesis of lung- one lung may be absent , if one bronchial bud fails to develop. 2> Hypoplasia of lung – lungs are small & underdeveloped. 3> Ectopic lung-it may arise from esophagus or trachea, due to additional/extra respiratory bud of trachea & foregut 4> Congenital polycystic lung- multiple cysts are formed in the lung due to abnormal dilatation of terminal bronchioles, giving HONEYCOMB appearance in radiograph. 5> Abnormal lobes of lung- sometimes Rt. Lung has two lobes while Lt. Lung has three lobes , it is due to abnormal division of principal bronchi into Lobar bronchi. 6> Azygos lobe of lung- normally upper lobe of Rt. Lung lies lateral to the azygos vein but when a part of this lobe lies medial to the azygos vein ,it forms the azygos lobe .

27. MATURATION OF LUNG It deals with histological & functional development of the lung. Maturation of lung is divided into four stages- 1> Psuedoglandular stage- period- 5-16 weeks of IUL 2> Canalicular stage- period 16-26 weeks of IUL 3> Terminal sac stage- period 26 week to birth . ( saccular stage) 4> Alveolar stage - period 8 month to childhood . . . (8 Years)

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29. Alveolar stage

30. 1- Pseudoglandular Period (5-16 weeks) Developing lungs somewhat resembles an exocrine gland during this period By 16 weeks all major elements of the lung have formed except those involved with gas exchange (Terminal bronchioles are formed, BUT no respiratory bronchioles or alveoli are present ) Respiration is not possible at this stage Fetuses born during this period cannot survive

31. CANALICULAR STAGE (16-26 Weeks) Each terminal bronchiole divide into 2 or more Respiratory bronchiole Respiratory bronchiole divide into Alveolar ducts. Lung is well vascularised Fetus born at this stage may or may not survive.

32. TERMINAL SAC STAGE( saccular stage) ( 26 weeks to Birth) Large number of terminal sacs (primitive alveoli) are formed Capillaries bulge into the developing sacs Epithelium of terminal sac become very thin ( simple squamous ) Close contact develops between epithelium of sac & capillary to permit adequate exchange of gases Fetus born at this stage survive Terminal sac lined mainly by type I alveolar epithelium(Type I pneumocyte ) & few type II alveolar epithelium (Type II Pneumocyte ) Type I pneumocyte (very thin or squamous epith .) take part in gasseous exchange Type II pneumocytes secrete SURFACTANT that decrease surface tension in alveoli.

33. ALVEOLAR STAGE . (8month to 8 years) 32weeks to 8 years Formation of true alveoli more &more(many) Many type II pneumocytes that produce sufficient amount of surfactant Free exchange of gasses occur across the blood-air barriers ( formed by epithelium of alveoli and endothelium of capillaries).

34. APPLIED RELATED TO MATURATION OF LUNG RESPIRATORY DISTRESS SYNDROME- Seen in premature newborn, due to insufficient amount of SURFACTANT , So surface tension is high leading to collapse of alveoli, as a result breathlessness occur in newborn. In this disease ,alveoli of lungs are often filled with fluid having high protein,which resembles glassy hyaline membrane. Hence RDS is also k/a HYALINE MEMBRANE DISEASE . NEWBORN with RDS is treated with either artificial surfactant or glucocorticoids injection (which stimulate surfactant production)

35. QUESTION A baby born at 6 months of gestation is having trouble breathing. Why? Ans --- due to insufficient amount of SURFACTANT, alveoli collapse—no gasseous exchange occur Sufficient amount of surfactant is produced after 7 month of IUL, ( alveolar stage)

36. Development of pleura After the formation of the head fold, the pericardium comes to lie on the ventral aspect of the embryo , and the pericardio -peritoneal canals wind backwards on either side of the foregut . The lung bud ,that arise from the foregut, now invaginate these canals. As the bud enlarge to form the lungs, the canals balloon out to form the pleural cavities Each pleural cavity now communicates with the pericardial cavity through the pericardio -pleural opening and with the peritoneal cavity through pleuro-peritonial opening Later on these openings are closed by formation of the pericardio -pleural membrane & pleuro -peritoneal membrane respectively.

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