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Reading

  • Human Embryology (2nd ed.) Larson Ch6: p127-149
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Ch11: p226-233
  • Before we Are Born (5th ed.) Moore and Persaud Ch12; p241-254
  • Essentials of Human Embryology Larson Ch6 p81-96
  • Human Embryology Fitzgerald and Fitzgerald Ch18 p113-118
  • Additional References- Selected, Lung Development, Respiratory Development
  • Search PubMed- Medline

Computer Activities

UNSW Embryology:

Embryo Images Unit:

Unit: Body Cavities

Objectives

  • Describe the development of the respiratory system from the endodermal and mesodermal components.
  • Describe the main steps in the development of the lungs.
  • Describe the development of the diaphragm and thoracic cavities.
  • List the respiratory changes before and after birth.
  • Describe the developmental aberrations responsible for the following malformations: tracheo - oesophageal fistula (T.O.F); oesphageal atresia; diaphragmatic hernia; lobar emphysema.

Learning activities

  • Summarise the changes in the respiratory system and the C.V.S. at birth.??
  • To discuss the main features of physiological maturation of the lung and the importance of this to fetal and newborn viability.
  • Examine the serial sections of human and pig with reference to the respiratory system.
  • Discuss the selected malformations; tracheo - oesophageal fistula (T.O.F.) diaphragmatic hernia and lobar emphysema giving special reference to the developmental aberrations causing the malformations to the individuals

Development of the Respiratory System

  • Week 4 laryngotracheal groove forms on floor foregut
  • Week 5 left and right lung buds push into the pericardioperitoneal canals (primordia of pleural cavity)
  • Week 6 descent of heart and lungs into thorax. Pleuroperitoneal foramen closes.
  • Week 7 enlargement of liver stops descent of heart and lungs.

Diaphragm- 5 elements contribute to the diaphragm

  • septum transversum- central tendon
  • 3rd to 5th somite- musculature of diaphragm
  • ventral pleural sac- connective tissue
  • mesentry of oesophagus- connective tissue around oesophasus and IVC
  • pleuroperitoneal membranes- connective tissue around central tendon

Blood Supply-

  • pulmonary system not "functional" until after birth
  • 6th aortic arch arteries generate pulmonary areries
  • veins drain into pulmonary vein then left atrium
  • branches from dorsal aorta generate bronchial arteries

Lung Histology-

  • 4 periods
    • 5-17 week pseudoglandular
    • 16-25 week canalicular
    • 24-40 week terminal sac
    • late fetal-8years alveolar
  • month 3-6 lungs appear glandular
  • end month 6 alveolar cells type 2 appear and begin to secrete surfactant

month 7 respiratory bronchioles proliferate and end in alveolar ducts and sacs

UNSW Embryology Program

| Pig Embryo | Human Embryo | Selected Human (high power)

Pig Embryo

B1,B2: Pharynx. Crest in ventral floor of pharynx formed by fusion of 3rd pharyngeal arches = hypopharyngeal eminence (precursor of root of tongue). Rathke's pouch = rudimentary adenohypophysis.

B3: Rudimentary thyroid ventral to aortic sac (also seen in B2, ventral to the hypopharyngeal eminence).

B4: Caudal pharynx compressed dorsoventrally.

B6: Further compression of ventral part of pharynx to form a fused epithelial lamina, the vocal fold. Note surrounding dense mesenchyme. Nasal placode.

B7: Glottis drawn off from pharyngeal foregut. Nasal placodes. Pulmonary arteries.

C1,C2: Commencement of trachea and oesophagus with dense mesenchyme. R. nasal pit.

C3,C4: Common cardinal vein in the posterior wall of the intraembryonic coelom - the pleuropericardial folds which contribute later to the formation of the pleura and pericardium. L. nasal pit. In C4, junction of R common cardinal vein with dorsal wall of sinus venosus.

C5: Smaller oesophagus, expanding trachea. Note ventral anchoring of attachment site is at the most cranial extension of the septum transversum. Note also that this attachment

now divides the intraembryonic coelom around the trachea into two canals, the L and R pleuro (pericardio-peritoneal) canals. (Canals are lined by coelomic mesothelium

and are continuous with whole I-E coelom - they will be referred to hereafter simply as coelomic canals). Note the pleuroperitoneal fold on the medial side of the R common cardinal vein - this fold will form part of the diaphragm.

C5,C6: Lateral extension of pulmonary mesenchyme is moulded to shape of coelomic canals.

R common cardinal draining directly into sinus venosus; L common cardinal vein with prominent L pleuropericardial fold. Oesophagus lumen obliterated (common site of oesophageal atresia and/or tracheo-oesophageal fistula). Prominent R pleuroperitoneal fold.

C7: Bifurcation of trachea into L, R lung buds. Junction of L common cardinal vein and L; of sinus venosus. Note dorsal extent of coelomic canals. Oesophagus lumen reappears caudal to bifurcation. Distinct R (smaller on L) pleuroperitoneal fold below the common cardinal vein.

Dl: R lung bud prominent. (L lung bud is more cranial, therefore R primary bronchus is more vertical than the left - cf. Gross Anatomy). note ventral anchoring of pulmonary mesenchyme to the septum transversum, in which is also embeddedthe sinus venous.

D3: Liver embedded in septum transversum (ventral border of septum transversum contributes to diaphragm).

G7: Rathke's pouch. Floor of pharynx with foramen caecum (remains of thyroglossal duct), and caudally to it, the hypopharyngeal eminence. L lungbud caudal to L atrium with attachment of pulmonary mesenchyme to septum transversum.

G6: Pharynx, initially compressed dorsoventrally then more caudally, compressed mediolaterally in region of dense mass of mesenchyme (cf B6). Tracheal bifurcation dorsal to sinus venosus. Attachment of pulmonary mesenchyme to septum transversum.

Human Embryo

 

A5: Bridge of nose. R and L olfactory bulbs from forebrain (cf. A4).

A6: Nose. Nasal septum. Nasal capsule. Olfactory epithelium lining roof of nasal cavity. Orbital part of the developing sphenoid bone (intramembranous ossification).

A7: Conchae. Nasal capsule and septum.

B1: Conchae. Optic nerve.

B2: Perpendicular plate of ethmoid cartilage. Adenohypophysis. Neurohypophysis. Ant. and post. walls of hypopophysial fossa. Lesser wings of sphenoid cartilage. Internal carotid arteries.

B4: Dorsum of tongue. Oropharynx communicating with naso-pharynx (cf. B3 - palatal processes not fused).

B5: Tongue with palatal processes at either side. Transverse (intrinsic) muscle of tongue.

Pharyngotympanic tubes.

B6: Tongue with transverse muscle, genioglossus muscle (medial) and hyoglossus muscle (lateral). Meckel's cartilage. Palatal processes. Note teeth enamel organs (dark masses at sides of tongue attachment).

B7: Transverse caudal pharynx. epiglottis. Hyoid musculature. Pharyngeal constrictor muscle. Submandibular gland.

C1: Pharynx. Pharyngeal constrictor muscle. laryngeal caecum (ventral). Arytenoid swellings in contact. Thyroid cartilage laminae (anterolateral), with superior horns (posterolateral). Hyoid cartilage. Internal jugular veins.

C2: Pharynx. Thyroid cartilage. Smaller laryngeal caecum (cf.C1). Carotid neurovascular bundle.

C3: Pharynx with its inferior constrictor muscle. Glottis region.

C4: (Section damaged) Oesophagus with muscle layer and trachea with thyroid gland laterally. Common carotid arteries. Vagus nerve. Internal jugular veins.

C5: Oesophagus, smaller than in C4. Trachea. Thyroid gland (isthmus). Clavicle. Small dark masses near posterolateral borders of thyroid gland are the parathyroid glands from the caudal part of 3rd pharyngeal pouch.

C6: Clavicles. Dark connecting stalk between parathyroid gland and thymus (rostral end

of 3rd pharyngeal pouch). Trachea. Common carotid artery.

C7: Sternum. Thymus gland. L brachiocephalic vein. Brachiocephalic trunk. Trachea.

Oesphagus. Apex of R lung in pleural cavity.

Dl: Sternum. Thymus. Lungs. Visceral and parietal pleurae. Pleural cavities. Other contents of superior mediastinum.

D3: Tracheal bifurcation.

D4: R primary bronchus (torn) and R superior lobe bronchus. L primary bronchus. L, R pulmonary arteries. Ribs joining to sternum.

D5: R, L primary bronchi. R anterior and posterior segmental bronchi coming off R superior lobe bronchus. L, R pulmonary arteries. Hilar attachments of lungs to mediastinal tissues - note extent of R, L pleural cavities.

D6: R, L primary bronchi (note left still has not branched). R pulmonary artery.

D7: R, L primary bronchi: note distinct horizontal course of L, vertical course of R, L pulmonary veins (L empty). R pulmonary artery.

E1,E2: Pulmonary veins. Azygos, hemiazygos veins. Ribs. Intercostal muscles.

E3: R dome of diaphragm. Liver. R long middle and inferior lobes. L long superior and inferior lobes. Xiphoid process.

E4: Diaphragm (note costal attachment). R lung inferior lobe. Inferior vena cava, dorsal to diaphragm.

E5: Liver. Diaphragm with sternal attachments. Inferior vena cava, now ventral to diaphragm (vena caval foramen). Inferior lobes of lungs.

E6: Liver. Thoracic aorta. Large adrenal glands.

E7: Lumbar diaphragm. Thoracic aorta. Note ribs 11 and 12 on L and three layers of abdominal muscles extending ventrally.

Fl: Lumbar diaphragm. Thoracic aorta.

F2: Attachment of lumbar diaphragm near L 1 on R with psoas muscle dorsal to it. Note abdominal aorta giving rise to superior mesenteric artery.

Human Embryo- high power

 

B7,C1: Laryngeal caecum. Arytenoid swellings. Thyroid cartilage. L,R laminae and superior processes. Hyoid cartilage with sternohyoid muscles.

C2,C3: Tracheal epithelium. Note in C2, ventral tracheal cartilage. In C3 note rounded cells of hyaline tracheal cartilage, starting to push apart in central midline zone but compressed together at lateral margins. Thyroid gland.

C4: Tracheal epithelium (vacuolated) and trachealis muscle. Note regional changes in

cartilage as in C3 above. Oesophagus - epithelium (vacuolated), submucosa and muscularis externa with a few inner spiral and isolated, outer longitudinal muscle bundles.

C5,C6: Developing thymus.

Dl: Note bronchial epithelium (tall wedge-shaped cells) with subepithelial smooth muscle, surrounding loose connective tissue and visceral pleura.

Self Assessment Questions

1. How is the trachea formed and what are the basic derivations of the lung?

2. How does the thoracic cavity develop?

3. What processes occur during the maturation of the lung in the fetus?

4. What is a tracheo-oesophageal fistula? How does this affect the amount of amniotic fluid present?

5. How is the larynx formed?

DEVELOPMENTAL ABNORMALITIES

 

I. TRACHEO-OESOPHAGEAL FISTULA (OESOPHAGEAL ATRESIA)

OMIM Database Entry- Tracheosophageal Fistula

Summary

Oesophageal atresia as suggested by

(a) Polyhydramnios
(b) Reflex increase in salivation
(c) Holdup of the catheter confirmed by the X-ray appearance of the dilated blind proximal oesophagus. The fistula is confirmed by the presence of gas in the intestines.

Management

1. Operative closure of the trachea end of the fistula.
2. Restoration of the continuity of the oesophagus
N.B. This is a serious malformation with significant risk of mortality

 Associated Malformations

(a) Stratified squamous epithelium and columnar epithelia (mixtures of tracheal and oesophageal epithelial) are found in the trachea and oesophagus.
(b) This often occurs as one of a complex of malformations in a child. The origin is in early embryogenesis and often associated with
(i) cloacal malformation
(ii) cardiac septal defects
(iii) renal malformations

Questions

(a) The failure of what embryological process might give rise to this malformation?

(b) Why is there almost invariable association of tracheo oesophageal fistula with polyhydramnios?

(c) Why is there an early onset of pneumonia if the malformation is unrecognised?

(d) How might the defect possibly be corrected?

II LOBAR EMPHYSEMA (Overinflated lung)

OMIM Database Entry- Lobar Emphysema

1. There is an overinflated left upper lobe
2. There is a collapsed lower lobe
3. The left lung is herniating across the mediastinum

 Description of lesion - there is a congenital deficiency of cartilage in the left upper lobe bronchus. The anatomical nature of the lesion was demonstrated by autopsy specimens and usually reveals no abnormality other than cartilage deficiency throughout the lobe.

Summary

(a) Respiration is normal at first
(b) Once distress occurs overinflation is rapidly progressive and may kill by asphyxia.
(c) This is called Lobar Emphysema due to congenital broncho-malacia (soft bronchi).

 Management

The affected lobe must be resected.

III. RESPIRATORY DISTRESS SYNDROME IN THE NEWBORN (Hyaline Membrane Disease)

Management

1. R.D.S. is normally treated conservatively with 02, intravenous bicarbonate and general supportive measures but the mortality rate is high in more premature infants. At autopsy the principle change to be seen is an eosinophilic hyaline membrane filling the alveoli.

2. If the child is treated with constant positive airway pressure this increases arterial 02 tension and helps prevent the collapse of alveoli which deficient surfactant otherwise causes. This increases the functional residual capacity of the lungs. This support system is effective in the nearly mature infants but the more premature still have a high mortality rate.

IV. CONGENITAL DIAPHRAGMATIC HERNIA

Failure of the pleuroperitoneal foramen (foramen of Bochdalek) to close allows viscera into thorax. Intestine, stomach or spleen can enter the pleural cavity, compressing the lung.

V. AZYGOS LOBE

Common condition (0.5% of population). The right lung upper lobe expands either side of the posterior cardinal.

Management

Condition is generally harmless.

OMIM Database Online Mendelian Inheritence in Man Database. OMIM

Internet Search OMIM database with the keyword "lung" or the above abnormality names.

Note: This database is an external link, not accessible from some computers in the School of Anatomy.
A List of the 570 entries found, searching for "lung" is available for these computers.

Respiratory Terms

  • atresia- obstruction.
  • eppiglottis- develops from hypobrachial eminence.
  • fistula- abnormal comunication.
  • laryngotracheal groove- forms on anterior (ventral) wall of pharynx, gives rise to larynx, trachea, respiratory tree.
  • larynx- lining from endoderm, cartilage from pharyngeal arch 4 and 6.
  • lung buds- primordia of lungs.
  • parietal pleura-outer lining of pleural cavity derived from epithelia of pericardioperitoneal canals from intraembryonic coelom.
  • pleural cavity- walls derived from pericardioperitoneal canals -> intraembryonic coelom ->coelomic spaces -> lateral mesoderm -> mesoderm.
  • pleuropericardial fold- restricts the communication between pleural cavity and pericardiac cavity, contains cardinal vein and phrenic nerve.
  • pleuroperitoneal membrane- forms inferiorly at transverse septum to separate peritoneum from pleural cavity.
  • septum transversum- mesoderm separating thoracic cavity and yolk sac, forms central tendon of diaphragm (and some of liver?).
  • stenosis- narrowing
  • surfactant- a detergent secreted by Type 2 alveolar cells between alveolar epithelium. Functions to lower surface tension, allowing lungs to remain inflated.
  • visceral pleura- inner lining of pleural cavity derived from contact epithelia with lung bud of pericardioperitoneal canals from intraembryonic coelom.

About Notes

  • Lecture notes from the Anat 3311 1997 Science Embryology course compiled and written by Dr Mark Hill. Some notes derived from historic class notes.
  • Note Links to OMIM Entries are copies of originals for computers without internet access. Computers with internet access can directly access the database.

Links
Serial Sections Homepage
Human Homepage
Pig Homepage

m.hill@unsw.edu.au
Date Last Modified: 11/3/99
This site maintained by Dr M. Hill