Lecture - Respiratory Development

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Introduction

adult lung structure
adult lung structure

The respiratory system does not carry out its physiological function (of gas exchange) until after birth and is filled with liquid and not air until then. Note that most of the respiratory system consists of the conductive "pipes", with the actual functional exchange unit (the alveolus, plural alveoli) forming at the very end of this plumbing right at the end of development.

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 alveoli (respiratory functional unit).

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


Some Recent Research Daniel R Chang, Denise Martinez Alanis, Rachel K Miller, Hong Ji, Haruhiko Akiyama, Pierre D McCrea, Jichao Chen Lung epithelial branching program antagonizes alveolar differentiation. Proc. Natl. Acad. Sci. U.S.A.: 2013; PMID:24058167


Lecture Objectives

Respiratory tract (Week 5)
  • Understanding of embryonic lung development
  • Understanding of the stages of lung development
  • Understanding of diaphragm development
  • Brief understanding of respiratory vascular development
  • Brief understanding of respiratory abnormalities
  • Brief understanding of molecular mechanisms

2014 Lecture 10 PDF

Lecture Resources

Movies
Stage13-GIT-icon.jpg
 ‎‎Gastrointestinal
Page | Play

Week 4-5 Stage 13

Stage22-GIT-icon.jpg
 ‎‎Gastrointestinal
Page | Play

Week 8 Stage 22

References
UNSW Embryology logo
Hill, M.A. (2014). UNSW Embryology (14th ed.) Retrieved September 23, 2014, from http://php.med.unsw.edu.au/embryology
Respiratory Links: Introduction | Science Lecture | Med Lecture | Stage 13 | Stage 22 | Upper Respiratory Tract | Diaphragm | Histology | Postnatal | Abnormalities | Respiratory Quiz | Category:Respiratory
Historic Embryology
1902 The Nasal Cavities and Olfactory Structures | 1912 Upper Respiratory Tract | 1912 Respiratory | 1918 Respiratory images | 1921 Respiratory | 1922 Chick Pulmonary Vessels
  • Lecture Archive:
Textbook cover The Developing Human, 9th edn.
Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders.
The following chapter links only work with a UNSW connection.
Textbook cover Larsen's human embryology 4th edn.
Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. & Francis-West, P.H. (2009). Larsen's human embryology (4th ed.). New York; Edinburgh: Churchill Livingstone.
The following chapter links only work with a UNSW connection.
Other Online Respiratory Resources
ECHO360 Recording
ECHO360 icon.gif

Links only work with currently enrolled UNSW students.

Lecture 8 -


Developmental Overview

About the Alveolus

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

Respiratory histology 03.jpg Alveolar-sac-01.jpg
Alveolus histology Alveolus structure
Lung primary lobule 01.jpg Lung secondary lobule 01.jpg
Primary Lobule - region supplied by a respiratory bronchiole Secondary Lobule - region supplied by a terminal bronchiole

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.

Events

  • 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.

Lung Development Stages

The sequence is most important rather than the actual timing, which is variable in the existing literature.

  1. week 4 - 5 embryonic
  2. week 5 - 17 pseudoglandular
  3. week 16 - 25 canalicular
  4. week 24 - 40 terminal sac
  5. late fetal - 8 years alveolar

Embryonic

  • 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.
Gray0982a.jpg Bailey287.jpg Bailey288.jpg Bailey289.jpg
Week 4 Week 4-5 (Stage 12 to 13) Week 5 (Stage 15 to 16) Week 6 (Stage 16 to 17)

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.
Stage 22 image 171.jpg

Lung structure (week 8)

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.
Fetal lung histology.jpg

Saccular stage

  • 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.
  • The vascular tree also grows in length and diameter during this time.
Lung alveoli development cartoon.jpg
Alveolar sac structure

Human Lung Stages

Stage Human Features
Embryonic week 4 to 5 lung buds originate as an outgrowth from the ventral wall of the foregut where lobar division occurs
Pseudoglandular week 5 to 17 conducting epithelial tubes surrounded by thick mesenchyme are formed, extensive airway branching
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
Saccular week 24 to 40 alveolar ducts and air sacs are developed
Alveolar late fetal to 8 years secondary septation occurs, marked increase of the number and size of capillaries and alveoli
         

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.

Upper respiratory tract

  • Oral cavity - palate development (early fetal) separates oral cavity from nasal cavity (covered in head development lecture).
  • Pharynx - bifurcation (esophagus, trachea) separates GIT from respiratory.
  • Trachea - bifurcation (left and right bronchi) separates the major lung branches.
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 head development lecture

Lower respiratory tract

Lung development stage13-22.jpg


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

(MH - do not need to know the values from table, just the increase in volume)

Pleural Cavity

pleura
pleura
  • The anatomical body cavity in which the lungs develop and lie.
  • The 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.


Pleura

  • 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

Diaphragm

  • 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

Fetal Respiratory Movements

  • Fetal respiratory movements (FRM) or Fetal breathing movements (FBM) are regular muscular contrations occurring in the third trimester.
  • thought to be preparing the respiratory muscular system for neonatal function
  • thought to 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).

  • Respiratory Rate is higher than adult (30 breaths/minute).
Postnatal alveoli number
Rib orientation

Alveoli

  • 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

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

Respiratory System - Abnormalities

Congenital diaphragmatic hernia
Lung Azygos Lobe
Preterm Birth
  • 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. Congenital Diaphragmatic Hernia | 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.

Mark D Miller, Melanie A Marty Impact of environmental chemicals on lung development. Environ. Health Perspect.: 2010, 118(8);1155-64 PMID:20444669


  1. C F A Peralta, P Cavoretto, B Csapo, O Falcon, K H Nicolaides Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12-32 weeks' gestation. Ultrasound Obstet Gynecol: 2006, 27(2);128-33 PMID:16388511


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Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved September 23, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development

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