SH Lecture - Respiratory System Development

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Respiratory tract

The lecture will introduce the development of the respiratory system and associated structures. The lecture will not cover adult anatomy, physiology of gas exchange, red blood cell function, cardiovascular development and will leave detailed histology to your associated practical class.

Research suggests that in addition to genetic effects that the developmental environment (both fetal and postnatal) can influence the growth, differentiation and function of this system.

Start Time/End Time: 10am to 11am Monday 11 March 2013 Clancy Auditorium Lecture Slides PDF

Lecture: Lecture 2013 PDF | 2012 | 2012 PDF (10 pages) | eMed Link to Learning Activity - Respiratory System Development
SH Links: Lymphatic Lecture | Lymphatics Practical Support | Respiratory Lecture | Respiratory Practical Support | Medicine

The respiratory system does not carry out its physiological function (of gas exchange) until after birth, though the respiratory tract, diaphragm and lungs do begin to form early in embryonic development and continue through fetal development, only functionally maturing just before birth. The lungs continue to grow postnatally through childhood and some research finding suggest that there remains potential for growth in the adult.

The respiratory tract is divided anatomically into 2 main parts:

  1. upper respiratory tract - consisting of the nose, nasal cavity and the pharynx.
  2. lower respiratory tract - consisting of the larynx, trachea, bronchi and the lungs.

The respiratory "system" usually includes descriptions of not only the functional development of the lungs, but also related musculoskeletal (diaphragm) and vascular (pulmonary) development.


adult lungs

To understand the prenatal and postnatal developmental anatomy of human respiratory organs.

Key Concepts

  1. Embryonic origin of respiratory components (tract, lungs, diaphragm, muscles)
  2. Key stages in respiratory development.
  3. Time course of respiratory development.
  4. Respiration at birth.
  5. Postnatal development of respiration.
  6. Developmental abnormalities.


Logo.png Hill, M.A. (2013) UNSW Embryology (13th ed.). Sydney:UNSW.
Respiratory Links: respiratory | Science Lecture | Lecture Movie | Med Lecture | Stage 13 | Stage 22 | upper respiratory tract | diaphragm | Histology | Postnatal | respiratory abnormalities | Respiratory Quiz | Respiratory terms | Category:Respiratory
Historic Embryology - Respiratory 
1902 The Nasal Cavities and Olfactory Structures | 1906 Lung | 1912 Upper Respiratory Tract | 1912 Respiratory | 1913 Prenatal and Neonatal Lung | 1914 Phrenic Nerve | 1918 Respiratory images | 1921 Respiratory | 1922 Chick Pulmonary Vessels | 1934 Right Fetal Lung | 1936 Early Human Lung | 1937 Terminal Air Passages | 1938 Human Histology
Larsen's human embryology 4th edn.jpg Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. and Francis-West, P.H. (2009). Larsen’s Human Embryology (4th ed.). New York; Edinburgh: Churchill Livingstone.
The Developing Human, 8th edn.jpg Moore, K.L. & Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8th ed.). Philadelphia: Saunders.

Respiratory Functional Unit

Alveolus (Latin alveolus = "little cavity", plural is alveoli)

Alveolar-sac-01.jpg Postnatal alveoli number.jpg
The alveoli cellular structure Increase in human alveoli number
Lung primary lobule 01.jpg Lung secondary lobule 01.jpg
Alveoli and blood vessels Lung structure

Developmental Overview

Week 5 Respiratory Development

Germ Layers

  • Endoderm and splanchnic mesoderm form majority of conducting and alveoli.
  • Ectoderm will contribute the neural innervation.
  • Mesoderm also contributes the supporting musculoskeletal components.
Bailey287.jpg Bailey288.jpg Bailey289.jpg
Week 4-5 (Stage 12 to 13) Week 5 (Stage 15 to 16) Week 6 (Stage 16 to 17)

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.

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.

Development Stages

Note - the sequence is important rather than the actual timing, which is variable in the existing literature.

Human Lung Stages
Lung Stage Human Features Vascular
Embryonic week 4 to 5 lung buds originate as an outgrowth from the ventral wall of the foregut where lobar division occurs extra pulmonary artery then lobular artery
Pseudoglandular week 5 to 17 conducting epithelial tubes surrounded by thick mesenchyme are formed, extensive airway branching Pre-acinar arteries
Canalicular week 16 to 25 bronchioles are produced, increasing number of capillaries in close contact with cuboidal epithelium and the beginning of alveolar epithelium development Intra-acinar arteries
Saccular week 24 to 40 alveolar ducts and air sacs are developed alveolar duct arteries
Alveolar late fetal to 8 years secondary septation occurs, marked increase of the number and size of capillaries and alveoli alveolar capillaries
embryonic stage - pseudoglandular stage - canalicular stage - saccular stage - alveolar stage   Links: Species Stage Comparison | respiratory
Lung alveoli development cartoon.jpg


  • week 4 - 5
  • Endoderm - tubular ventral growth from foregut pharynx.
  • Mesoderm - mesenchyme of lung buds.
  • Intraembryonic coelom - pleural cavities elongated spaces connecting pericardial and peritoneal spaces.

Pseudoglandular stage

  • week 5 - 17
  • tubular branching of the human lung airways continues
  • by 2 months all segmental bronchi are present.
  • lungs have appearance of a glandlike structure.
  • stage is critical for the formation of all conducting airways.
    • lined with tall columnar epithelium
    • more distal structures are lined with cuboidal epithelium.

Canalicular stage

  • week 16 - 24
  • Lung morphology changes dramatically
  • differentiation of the pulmonary epithelium results in the formation of the future air-blood tissue barrier.
  • Surfactant synthesis and the canalization of the lung parenchyma by capillaries begin.
  • future gas exchange regions can be distinguished from the future conducting airways of the lungs.

Saccular stage

Alveolar sac structure
  • week 24 to near term.
  • most peripheral airways form widened "airspaces", termed saccules.
  • saccules widen and lengthen the airspace (by the addition of new generations).
  • future gas exchange region expands significantly.
  • Fibroblastic cells also undergo differentiation, they produce extracellular matrix, collagen, and elastin.
    • May have a role in epithelial differentiation and control of surfactant secretion.
  • Alveolar Cells Type II (Type II pneumocytes)
    • begin to secrete surfactant, levels of secretion gradually increase to term.
    • allows alveoli to remain inflated
  • Vascular tree - also grows in length and diameter during this time.

Alveolar stage

  • late fetal to 8 years.
  • The postnatal lung, with alveoli forming.
  • Expansion of gas exchange alveoli, vascular beds (capillaries), lymphatics and innervation.

Foregut Development

Foregut cartoon

From the oral cavity the next portion of the foregut is initially a single gastrointestinal (oesophagus) and respiratory (trachea) common tube, the pharynx which lies behind the heart. Note that the respiratory tract will form from a ventral bud arising at this level.

  • Oral cavity
  • Pharynx (esophagus, trachea)
  • Respiratory tract
  • Stomach

Upper Respiratory Tract

Adult upper respiratory tract conducting system
  • part of foregut development
  • anatomically the nose, nasal cavity and the pharynx
  • the pharynx forms a major arched cavity within the pharyngeal arches (MH - pharyngeal arches will be described in BGD head development lecture).

Lower Respiratory Tract

Lung development stage13-22.jpg Stage 22 image 171.jpg
Stage 13 (Week 4-5) Stage 22 (Week 8)
Lung alveoli development cartoon
Fetal lung histology
  • lung buds ( endoderm epithelial tubes) grow/push into mesenchyme covered with pleural cells (lung border)
  • generates a tree-like network by repeated:
  1. elongation
  2. terminal bifurcation
  3. lateral budding

Growth initially of branched "conducting" system of bronchial tree, followed by later development of the "functional units" of the alveoli.

Fetal Lung Volume

Each human lung volume as determined by ultrasound and matched to gestational age [1]

Weeks (gestational) Volume (ml)
12 to 13 0.05
19 to 22 0.5
29 to 32 1.9
Lung volume graph 01.jpg

Pleural Cavity

  • anatomical body cavity in which the lungs develop and lie.
  • pleural cavity forms in the lateral plate mesoderm as part of the early single intraembryonic coelom.
  • This cavity is initially continuous with pericardial and peritoneal cavities and form initially as two narrow canals.
    • later becomes separated by folding (pleuropericardial fold, pleuroperitoneal membrane) and the later formation of the diaphragm.
  • pleuropericardial fold - (pleuropericardial membrane) An early embryonic fold which restricts the communication between pleural cavity and pericardiac cavity, contains both the cardinal vein and phrenic nerve.
  • pleuroperitoneal membrane - An early embryonic membrane that forms inferiorly at the septum transversum to separate peritoneal cavity from pleural cavity.


  • serous membrane covers the surface of the lung and the spaces between the lobes.
  • arranged as a closed invaginated sac.
  • two layers (pulmonary, parietal) continuous with each other, the potential space between them is the pleural cavity.


  • Not respiratory tract but musculoskeletal development, there are 5 embryonic elements that contribute to the diaphragm.
Components of the diaphragm
  1. septum transversum- central tendon
  2. 3rd to 5th somite- musculature of diaphragm
  3. ventral pleural sac- connective tissue
  4. mesentry of oesophagus- connective tissue around oesophasus and IVC
  5. pleuroperitoneal membranes- connective tissue around central tendon
Adult Cervical Plexus (phrenic nerve shown lower right)

adult diaphragm

  • Innervation of the human diaphragm is by the phrenic nerves
    • arising from the same segmental levels from which the diaphragm skeletal muscles arise, segmental levels C3 to C5.
  • The paired phrenic nerves are mixed nerves
    • motor neurons for the diaphragm
    • sensory nerves for other abdominal structures (mediastinum, pleura, liver, gall bladder).

Pulmonary Circulation

Pulmonary circulation
  • the pulmonary system not "functional" until after birth
  • pulmonary arteries - 6th aortic arch arteries
  • pulmonary veins - are incorporated into the left atrium wall
  • bronchial arteries - branches from dorsal aorta


Fetal Respiratory Movements

  • Fetal respiratory movements (FRM) or Fetal breathing movements (FBM) are regular muscular contrations occurring in the third trimester.
  • preparing the respiratory muscular system for neonatal function.
  • may also have a role in late lung development.

The First Breath

Alveolar sac structure
  • The respiratory system does not carry out its physiological function (gas exchange) prenatally and remain entirely fluid-filled until birth.
  • At birth, fluid in the upper respiratory tract is expired and fluid in the lung aveoli is rapidly absorbed this event has also been called "dewatering of the lung".
    • The lung epithelia has to now rapidly change from its prenatal secretory function to that of fluid absorbtion.

The exchange of lung fluid for air leads to:

  • fall in pulmonary vascular resistance
  • increase in pulmonary blood flow
  • thinning of pulmonary arteries (stretching as lungs increase in size)
  • blood fills the alveolar capillaries

In the heart - pressure in the right side of the heart decreases and pressure in the left side of the heart increases (more blood returning from pulmonary).


Postnatal alveoli number
Rib orientation


  • At birth about 15% of adult alveoli number have formed
    • 20 - 50 million to in the adult about 300 million.
  • remaining subdivisions develop in the first few postnatal years

Alveoli Number

Respiratory Rate

  • neonatal rate is higher (30-60 breaths/minute) than adult (12-20 breaths/minute).
    • tachypnea - (Greek, rapid breathing) an increased respiratory rate of greater than 60 breaths/minute in a quiet resting baby
Age Rate (breaths/minute)
Infant (birth - 1 year) 30 - 60
Toddler (1 - 3 years) 24 - 40
Preschool (3 - 6 years) 22 - 34
School age (6 - 12 years) 18 - 30
Adolescent (12 - 18 years) 12 - 16

Rib Orientation

  • Infant rib - is virtually horizontal, allowing diaphragmatic breathing only.
  • Adult rib - is oblique (both anterior and lateral views), allows for pump-handle and bucket handle types of inspiration.

Respiratory Tract Abnormalities

Lung Azygos Lobe

Respiratory System - Abnormalities

  • Meconium Aspiration Syndrome - (MAS) Meconium is the gastrointestinal contents that accumulate in the intestines during the fetal period. Fetal stress in the third trimester, prior to/at/ or during parturition can lead to premature meconium discharge into the amniotic fluid and sunsequent ingestion by the fetus and damage to respiratory function. Damage to placental vessels meconium myonecrosis may also occur.
  • Newborn Respiratory Distress Syndrome - (Hyaline Membrane Disease) membrane-like substance from damaged pulmonary cells, absence of surfactant, if prolonged can be irreversible, intrauterine asphyxia, prematurity and maternal diabetes medline plus | eMedicine
  • Tracheoesophageal Fistula - Tracheo-Oesophageal Fistula, Oesophageal Atresia - Oesophageal Atresia with or without tracheo-oesophageal fistula Fistula - an abnormal communication between 2 structures (organs, vessels, cavities) that do not normally connect.
  • Lobar Emphysema (Overinflated Lung) - There is an overinflated left upper lobe There is a collapsed lower lobe The left lung is herniating across the mediastinum
  • Congenital Diaphragmatic Hernia - (1 in 3,000 live births) Failure of the pleuroperitoneal foramen (foramen of Bochdalek) to close (left side), allows viscera into thorax -iIntestine, stomach or spleen can enter the pleural cavity, compressing the lung. rare (Morgagni hernia) -an opening in the front of the diaphragm. GeneReviews
  • Azygos Lobe - Common condition (0.5% of population). The right lung upper lobe expands either side of the posterior cardinal. There is also some course variability of the phrenic nerve in the presence of an azygos lobe.
  • Congenital Laryngeal Webs - Laryngeal abnormality due to embryonic (week 10) incomplete recanalization of the laryngotracheal tube during the fetal period. Rare abnormality occuring mainly at the level of the vocal folds (glottis).
  • Hyaline Membrane Disease - (Newborn Respiratory Distress Syndrome) a membrane-like substance from damaged pulmonary cells.
  • Bronchopulmonary Dysplasia - A chronic lung disease which can occur following premature birth and related lung injury. Most infants who develop BPD are born more than 10 weeks before their due dates, weigh less than 1,000 grams (about 2 pounds) at birth, and have breathing problems.
  • Asthma - Flow limitation during tidal expiration in early life significantly associated with the development of physician-diagnosed asthma by the age of 2 years. Infants with abnormal lung function soon after birth may have a genetic predisposition to asthma or other airway abnormalities that predict the risk of subsequent lower respiratory tract illness. PMID 8176553
  • Cystic Fibrosis - Inherited disease of the mucus and sweat glands, causes mucus to be thick and sticky. Clogging the lungs, causing breathing problems and encouraging bacterial grow. (Covered elsewhere in the course)
  • Environmental Factors see recent review below. <pubmed>20444669</pubmed>

Additional Information

Respiratory Quiz

Glossary Links

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Cite this page: Hill, M.A. (2021, March 4) Embryology SH Lecture - Respiratory System Development. Retrieved from

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© Dr Mark Hill 2021, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
  1. <pubmed>16388511</pubmed>