Difference between revisions of "SH Lecture - Respiratory System Development"

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{{Header}}
 
==Introduction==
 
==Introduction==
[[Image:Mark Hill.jpg|100px|left]]
+
[[File:Fetal head section 01.jpg|thumb|300px|Fetal Pharynx (week 12)]]
[[File:Respiratory tract.jpg|thumb|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 and red blood cell function and cardiovascular development.
+
| [[File:SHsmall.jpg]]
 +
| 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.
 +
| [[Image:Mark Hill.jpg|80px]]
 +
|}
 +
 
  
:{{Template:SH2011}}
+
:''Current research suggests that both genetic and the developmental environment (fetal and postnatal) can influence the growth, differentiation and function of the respiratory system.''
  
Start Time/End Time: 10am to 11am Thursday 1 March 2012 Clancy Auditorium  [http://emed.med.unsw.edu.au/Map.nsf/0/6FF17DFEF645DABACA2573390006292A?OpenDocument&login eMed Link to Learning Activity - Respiratory System Development]
+
{|
 +
! Lower respiratory tract
 +
! Respiratory tree
 +
|-
 +
| [[File:Bronchi_lungs.jpg|thumb|300px]]
 +
| [[File:Respiratory tract.jpg|thumb|300px]]
 +
|}
  
 +
[[Media:SH Lecture 2019 - Respiratory System Development.pdf|'''2019 Respiratory Development Lecture PDF''']]
  
 +
{| class="wikitable mw-collapsible mw-collapsed"
 +
! Lecture Archive  
 +
|-
 +
| [https://embryology.med.unsw.edu.au/embryology/index.php?title=SH_Lecture_-_Respiratory_System_Development&oldid=326862 2018] | [[Media:SH Lecture 2018 - Respiratory System Development.pdf|2018 PDF]] | [https://embryology.med.unsw.edu.au/embryology/index.php?title=SH_Lecture_-_Respiratory_System_Development&oldid=282832 2017] | [[Media:SH Lecture 2017 - Respiratory System Development.pdf|2017 PDF]] | [https://embryology.med.unsw.edu.au/embryology/index.php?title=SH_Lecture_-_Respiratory_System_Development&oldid=220801 2016] | [[Media:SH Lecture 2016 - Respiratory System Development.pdf|2016 PDF]] | [https://embryology.med.unsw.edu.au/embryology/index.php?title=SH_Lecture_-_Respiratory_System_Development&oldid=175983 2015] | [[Media:SH Lecture 2015 - Respiratory System Development.pdf|2015 PDF]] | [https://embryology.med.unsw.edu.au/embryology/index.php?title=SH_Lecture_-_Respiratory_System_Development&oldid=143114 2014] | [[Media:SH Lecture 2014 - Respiratory System Development.pdf|Lecture 2014 PDF]] | [[Media:SH Lecture 2013 - Respiratory System Development.pdf|2013 PDF]] | [http://embryology.med.unsw.edu.au/embryology/index.php?title=SH_Lecture_-_Respiratory_System_Development&oldid=119314 2013] | [http://php.med.unsw.edu.au/embryology/index.php?title=SH_Lecture_-_Respiratory_System_Development&oldid=98850 2012] | [[Media:SH Lecture - Respiratory System Development 2012.pdf|2012 PDF (10 pages)]] | [http://emed.med.unsw.edu.au/Map.nsf/0/6FF17DFEF645DABACA2573390006292A?OpenDocument&login eMed Link to Learning Activity - Respiratory System Development]
 +
|}
  
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.
+
{{SH2011}}
 +
 
 +
 
 +
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:  
 
The respiratory tract is divided anatomically into 2 main parts:  
Line 19: Line 38:
 
The respiratory "system"  usually includes descriptions of not only the functional development of the lungs, but also related musculoskeletal (diaphragm) and vascular (pulmonary) development.
 
The respiratory "system"  usually includes descriptions of not only the functional development of the lungs, but also related musculoskeletal (diaphragm) and vascular (pulmonary) development.
  
===Aims===
+
{|
[[File:Historic-lungs.jpg|thumb|adult lungs]]
+
| valign=top|
 +
===Aim===
 
To understand the prenatal and postnatal developmental anatomy of human respiratory organs.
 
To understand the prenatal and postnatal developmental anatomy of human respiratory organs.
 +
 +
{| class="wikitable mw-collapsible mw-collapsed"
 +
! colspan=2| Textbooks  
 +
|-
 +
| [[File:Logo.png|80px]]
 +
| {{Embryo citation}}
 +
 +
{{Respiratory Links}}
 +
|-
 +
| [[File:The Developing Human, 10th edn.jpg|90px]]
 +
| {{MPT2015APAcitation}}
 +
* Chapter 10  [http://ebookcentral.proquest.com.wwwproxy1.library.unsw.edu.au/lib/unsw/reader.action?docID=2074364&ppg=269 Respiratory System]
 +
* Chapter 8 [http://ebookcentral.proquest.com.wwwproxy1.library.unsw.edu.au/lib/unsw/reader.action?docID=2074364&ppg=198 Body Cavities and Diaphragm]
 +
* Chapter 9 [http://ebookcentral.proquest.com.wwwproxy1.library.unsw.edu.au/lib/unsw/reader.action?docID=2074364&ppg=216 Pharyngeal Apparatus, Face, and Neck]
 +
|-
 +
| [[File:Larsen's human embryology 5th ed.jpg|90px]]
 +
| {{SBBF2015APAcitation}}
 +
*  Chapter 11  [http://ebookcentral.proquest.com.wwwproxy1.library.unsw.edu.au/lib/unsw/reader.action?docID=2074524&ppg=269 Development of the Respiratory System and Body Cavities]
 +
|-
 +
| Additional Textbooks
 +
|
 +
* Paramothayan, S. (2018). Essential respiratory medicine. [https://ebookcentral.proquest.com/lib/unsw/reader.action?docID=5571252&ppg=21 CHAPTER 2 Embryology, anatomy, and physiology of the lung]
 +
* Histology and cell biology: An introduction to pathology  [http://www.unsw.eblib.com.wwwproxy0.library.unsw.edu.au/patron/Read.aspx?p=1430108&pg=404 Chapter 13. Respiratory System]
 +
* Developmental Biology 8e Online[http://8e.devbio.com/article.php?ch=15&id=157 Lung Branching Morphogenesis]
 +
* Before We Are Born (5th ed.) Moore and Persaud Chapter 13 p255-287
 +
* Essentials of Human Embryology Larson Chapter 9 p123-146
 +
* Human Embryology Fitzgerald and Fitzgerald Chapter 19, 20 p119-123
 +
|-
 +
| Review article
 +
|
 +
* 2017 [www.lungmap.net LungMAP]: The Molecular Atlas of Lung Development Program.{{#pmid:28798251|PMID28798251}}
 +
* 2017 Development of the lung.{{#pmid:28144783|PMID28144783}}
 +
* 2017 Developmental pathways in lung regeneration.{{#pmid:27957616|PMID27957616}}
 +
* 2017 In utero alcohol effects on foetal, neonatal and childhood lung disease.{{#pmid:27613232|PMID27613232}}
 +
* 2014 Lung development: orchestrating the generation and regeneration of a complex organ.{{#pmid:24449833|PMID24449833}}
 +
 +
|}
 +
 +
|
 
===Key Concepts===
 
===Key Concepts===
# Embryonic origin of respiratory components (tract, lungs, diaphragm, muscles)
+
# upper and lower respiratory tract.
 +
# Embryonic origin of respiratory components (tract, lungs, diaphragm, muscles).
 
# Key stages in respiratory development.
 
# Key stages in respiratory development.
 
# Time course of respiratory development.
 
# Time course of respiratory development.
Line 29: Line 89:
 
# Postnatal development of respiration.
 
# Postnatal development of respiration.
 
# Developmental abnormalities.
 
# Developmental abnormalities.
 +
|}
  
 +
==Respiratory Functional Unit ==
 +
===Alveolus===
 +
'''Alveolus''' (Latin ''alveolus'' = "little cavity", plural is alveoli)
 +
{|
 +
| [[File:Respiratory_histology_03.jpg|400px]]
 +
| [[File:Alveolar-sac-01.jpg|400px]]
 +
|-
 +
| Alveolus histology
 +
| Alveolus structure
 +
|}
  
[[File:Gray0974.jpg|thumb|lung structure]]
+
'''Inter-Alveolar Septum'''{{#pmid:30390118|PMID30390118}}
[[File:Gray0975.jpg|thumb|alveoli and blood vessels]]
 
  
==Textbooks==
+
[[File:Human lung inter-alveolar septum em01.jpg|600px]]
  
{|
+
Septum containing Type I (AEC1) and type II (AEC2) alveolar epithelial cell, alveolar lumen (Alv), capillary lumen (Cap), capillary endothelial cell (Endo ). Lamellar bodies (LB) in type II cell. Arrowheads mark tight junctions between type II and type I cell. Collagen fibrils (col) are present in the interstitium. Transmission electron microscopy. Scale bar 2 µm
| [[File:The Developing Human, 8th edn.jpg|80px]]
 
| Moore, K.L. &amp; Persuad, T.V.N. (2008). <i>The Developing Human: clinically oriented embryology</i> (8<sup>th</sup> ed.). Philadelphia: Saunders.
 
  
* [http://www.mdconsult.com/books/linkTo?type=bookPage&amp;isbn=978-1-4160-3706-4&amp;eid=4-u1.0-B978-1-4160-3706-4..50013-X Chapter 10 - The Respiratory System] (chapter links only work with a UNSW connection).
 
|-
 
| [[File:Larsen's human embryology 4th edn.jpg|80px]]
 
| Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. and Francis-West, P.H. (2009). <i>Larsen’s Human Embryology</i>  (4<sup>th</sup> ed.). New York; Edinburgh: Churchill Livingstone.
 
  
* [http://www.mdconsult.com/books/linkTo?type=bookPage&isbn=978-0-443-06811-9&eid=4-u1.0-B978-0-443-06811-9..10011-9 Chapter 11 - Development of the Respiratory System and Body Cavities] (chapter links only work with a UNSW connection).
+
{|
 +
| [[File:Lung_primary_lobule_01.jpg|300px]]
 +
| [[File:Lung_secondary_lobule_01.jpg|300px]]
 
|-
 
|-
| [[File:Logo.png|80px]]
+
| valign=top|'''Primary Lobule'''
| Hill, M.A. (2011) <i>UNSW Embryology</i> (11<sup>th</sup> ed.). Sydney:UNSW.
+
* region supplied by a '''respiratory bronchiole'''
 +
| '''Secondary Lobule'''
 +
* region supplied by a '''terminal bronchiole'''
 +
* size -  up to 2.5 cm across.
 +
* connective tissue - bounded by fibrous (interlobular) septa and containing finer internal septa.
 +
* lobule contains a up to 12 acini and 30 - 50 [[:File:Lung primary lobule 01.jpg|primary lobules]].
 +
* blood supply - pulmonary artery branch
 +
* blood drainage - pulmonary veins located at lobule periphery leave though the interlobular septa.  
 +
* lymphatics - arterial and interlobular septa associated (drain to subpleural plexus).
  
* {{Respiratory Links}}
 
 
|}
 
|}
  
===Additional Textbooks===
+
==Developmental Overview==
 +
[[File:Lung_alveoli_development_cartoon.jpg|thumb|300px]]
 +
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.
  
* Before We Are Born (5th ed.) Moore and Persaud Chapter 13 p255-287
 
* Essentials of Human Embryology Larson Chapter 9 p123-146
 
* Human Embryology Fitzgerald and Fitzgerald Chapter 19,20 p119-123
 
* Developmental Biology 8e Online[http://8e.devbio.com/article.php?ch=15&id=157 Lung Branching Morphogenesis]
 
* Anatomy of the Human Body 1918 Henry Gray [http://www.bartleby.com/107/235.html 1. The Respiratory Apparatus]
 
* [http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Respiratory/respir.htm Blue Histology - Respiratory]
 
 
==Developmental Overview==
 
 
'''Week 4''' - laryngotracheal groove forms on floor foregut.
 
'''Week 4''' - laryngotracheal groove forms on floor foregut.
  
Line 75: Line 145:
 
'''Month 7''' - respiratory bronchioles proliferate and end in alveolar ducts and sacs.
 
'''Month 7''' - respiratory bronchioles proliferate and end in alveolar ducts and sacs.
  
===Lung Development===
+
==Development Stages==
 +
Note - the sequence is important rather than the actual timing, which is variable in the existing literature.
 +
{{lung stage table}}
 +
 
 +
{|
 +
! Lung Stages - timing, airway and vascular development{{#pmid:30390117|PMID30390117}}
 +
|-
 +
| [[File:Human lung stages 01.jpg|800px]]
 +
|}
 +
===Embryonic===
 +
Week 4 to 5 - lung buds originate as an outgrowth from the ventral wall of the foregut where lobar division occurs.
 +
 
 +
{|
 +
| colspan=2|[[File:Endoderm_cartoon.jpg|alt=Endoderm development cartoon|link=Endoderm_Development_Movie]]
 +
|
 +
|-
 +
| [[File:Stage11_bf9.jpg|300px]]
 +
| [[File:Stage11_sem4.jpg|300px]]
 +
|-
 +
| Stomodeum (Week 4, stage 11, {{GA}} week 6)
 +
| Buccopharyngeal membrane  (Week 4, stage 11, {{GA}} week 6)
 +
|}
 +
 
 +
[[File:Stage14 respiratory tract.jpg|300px|Week 5 Respiratory Development]]
 +
 
 +
(Week 5, stage 14, {{GA}} week 7)
 +
* '''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.
 +
 
 +
[[Stage_13_MRI_Movie_1|Stage 13 - Trachea and Lung buds]] (MRI sagittal sections)
 +
 
 +
{|
 +
| [[File:Gray0982a.jpg|200px]]
 +
| [[File:Bailey287.jpg|200px]]
 +
| [[File:Bailey288.jpg|200px]]
 +
| [[File:Bailey289.jpg|200px]]
 +
|-
 +
| Week 4
 +
| Week 4-5 (Stage [[Carnegie_stage_12|12]] to [[Carnegie_stage_13|13]])
 +
| Week 5 (Stage [[Carnegie_stage_15|15]] to [[Carnegie_stage_16|16]])
 +
| Week 6 (Stage [[Carnegie_stage_16|16]] to [[Carnegie_stage_17|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'''.
 +
 
 +
* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733720/figure/F1/ Pulmonary neuroendocrine cells] (PNECs) - develop in late embryonic to early fetal period, later in mid-fetal period clusters of these cells form [neuroepithelial bodies (NEBs) in airway epithelium. May stimulate mitosis to increase branching, secrete 2 peptides - gastrin-releasing peptide (GRP) and calcitonin gene related peptide (CGRP).
 +
 
 +
 
 +
[[File:ME54 001.jpg|400px]]
 +
 
 +
Week 8
 +
| [[File:Fetal lung histology.jpg|300px]]
 +
 
 +
Fetal lung histology
 +
|}
 +
 
 +
([[:File:Parotid gland histology 06.jpg|This is what a gland looks like.]])
 +
 
 +
<br>
 +
{| class="wikitable mw-collapsible mw-collapsed"
 +
! Pseudoglandular and Canalicular Stages &nbsp;
 +
|-
 +
| Canalicular phase of bronchus can be mixed with the pseudoglandular phase.
 +
[[File:Pulmonary Pleura - pseudoglandular and canalicular stages 02.jpg|500px]]
 +
 
 +
Human Lung showing a mix of pseudoglandular and canalicular stages{{#pmid:30310706|PMID30310706}}
 +
|}
 +
===Canalicular stage===
 +
{|
 +
|
 +
* '''week 16 - 24'''
 +
* Lung morphology changes dramatically
 +
* differentiation of the pulmonary epithelium results in the first formation of the future air-blood tissue barrier.
 +
* '''Surfactant''' synthesis and the canalization of the lung parenchyma by capillaries begins.
 +
* future gas exchange regions can be distinguished from the future conducting airways of the lungs.
 +
 
 +
| [[File:Lung - canalicular stage.jpg|400px]]
 +
|}
 +
===Saccular stage===
 +
[[File:Alveolar-sac-01.jpg|thumb|300px|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===
 +
[[File:Respiratory secondary septum 01.jpg|thumb|300px|Secondary septum]]
 +
{|
 +
|
 +
* late fetal to 8 years.
 +
* Secondary septum
 +
* Expansion of gas exchange alveoli, vascular beds (capillaries), lymphatics and innervation.
 +
* Postnatal lung, with '''alveoli''' forming.
 +
| [[File:Postnatal_alveoli_number.jpg|400px]]
 +
|}
 +
 
 +
==Upper Respiratory Tract==
 +
[[File:Head arches cartoon.jpg|thumb|Foregut cartoon]]
 +
[[File:Pharynx_cartoon.jpg|thumb|Pharynx]]
 +
'''Foregut Development''' - 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.
 +
{|
 +
| [[File:Pharynx.jpg|Pharynx|400px]]
 +
|
 +
* part of '''foregut''' development  (Oral cavity, Pharynx (esophagus, trachea), Respiratory tract, Stomach)
 +
* anatomically the nose, nasal cavity and the pharynx
 +
* '''pharynx''' forms a major arched cavity within the pharyngeal arches ('''MH''' - pharyngeal arches will be described in BGD head development lecture).
 +
* '''palate''' - development for mammals, allows breathing while feeding.
  
* week 4 - 5 embryonic
+
Note - Specialised '''olfactory epithelium''' for smell, a small region located in roof of nasal cavity.
* week 5 - 17 pseudoglandular
+
|-
* week 16 - 25 canalicular
+
| [[File:Respiratory histology 11.jpg|300px]]
* week 24 - 40 terminal sac
+
| valign=top|'''Respiratory epithelium'''
* late fetal - 8 years alveolar
 
  
===Germ Layers===
+
* pseudo-stratified
* Endoderm form epithelium of conducting and alveoli.
+
* ciliated cells
* Ectoderm will contribute the neural innervation.
+
* goblet cells
* Mesoderm contributes connective tissues, blood vessels, smooth muscle, also contributes the supporting musculoskeletal components.
+
* basal cells
  
==Foregut development==
+
[[File:Respiratory epithelium cells cartoon.jpg|200px]]
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
+
Respiratory epithelium development
* Pharynx (esophagus, trachea)
 
* Respiratory tract
 
* Stomach
 
  
==Upper respiratory tract==
+
|}
 
<gallery>
 
<gallery>
File:Gray0961.jpg|Adult upper respiratory tract conducting system
 
File:Gitbpm.jpg|stage 11 foregut
 
File:Gray0982a.jpg|week 4 early respiratory endodermal bud
 
File:Head_arches_cartoon.jpg|Head arches cartoon
 
File:Pharynx_cartoon.jpg|Pharynx
 
 
File:Nasal cavities.jpg|Nasal cavities
 
File:Nasal cavities.jpg|Nasal cavities
File:Pharynx.jpg|Pharynx
 
 
File:Larynx.jpg|Larynx
 
File:Larynx.jpg|Larynx
 +
File:Gray0961.jpg|Adult upper respiratory tract conducting system
 +
</gallery>
 +
 +
 +
{| class="wikitable mw-collapsible mw-collapsed"
 +
!  Additional Information - Histology
 +
|-
 +
| This will be covered in detail in your associated SH Practical class.
 +
<gallery>
 +
File:Respiratory histology 13.jpg|Olfactory Epithelium
 +
File:Respiratory histology 14.jpg|Olfactory Epithelium
 +
File:Respiratory histology 11.jpg|Respiratory Epithelium
 +
File:Respiratory histology 12.jpg|Respiratory Epithelium
 
</gallery>
 
</gallery>
* part of foregut development
 
* anatomically the nose, nasal cavity and the pharynx
 
* the pharynx forms a major arched cavity within the pharyngeal arches (pharyngeal arches will be described in head development lecture)
 
  
 
{|
 
{|
| <wikiflv width="280" height="322" autostart="true" position="left">Endoderm 002.flv|File:Endoderm 002 icon.jpg</wikiflv>
+
|-
| [[File:Endoderm_cartoon.jpg]]
+
| valign=top width=380px|'''Olfactory epithelium'''
 +
* Olfactory cells
 +
* Sustentacular cells - located mainly in the superficial cell layer of the epithelium (difficult to distinguish from olfactory cells).
 +
* Basal cells - identified by their location in the epithelium.
 +
 
 +
'''Epithelium'''
 +
* Cilia are not visible
 +
* goblet cells are absent from the olfactory epithelium.
 +
 
 +
'''Lamina Propria'''
 +
* olfactory axon bundles (lightly stained, rounded areas) connected to olfactory cells.
 +
* Bowman's glands - (small mucous glands, olfactory glands) function to moisturise the epithelium.
 +
 
 +
{{Nasal olfactory links}}
 +
 
 +
| valign=top width=380px|'''Respiratory epithelium'''
 +
* goblet cells
 +
* ciliated cells
 +
* basal cells
 +
 
 +
'''Lamina propria'''
 +
* connective tissue
 +
* cavernous sinusoids - large spaces (empty or filled with red blood cells)
 +
* glandular tissue - mucous glands (green) and muco-serous glands (brownish-green)
 +
 
 +
'''Bone'''
 +
* Lamellae and osteocytes in lacunae.
 +
* Haversian systems are rare or absent.
  
[[Quicktime Development_Animation_-_Endoderm|Quicktime]] | [[Development_Animation_-_Endoderm|Flash]]
+
{{Nasal respiratory links}}
 
|}
 
|}
  
==Lower respiratory tract==
+
{{Respiratory Histology}}
 +
 
 +
|}
 +
 
 +
==Lower Respiratory Tract==
 
<gallery>
 
<gallery>
 
File:Gray0982a.jpg|week 4 early respiratory endodermal bud
 
File:Gray0982a.jpg|week 4 early respiratory endodermal bud
 
File:Gray0982b.jpg|week 4 later ventral endoderm growth
 
File:Gray0982b.jpg|week 4 later ventral endoderm growth
File:Stage14 respiratory tract.jpg|Developing lung buds
 
 
File:Bronchi lungs.jpg|lower respiratory tract
 
File:Bronchi lungs.jpg|lower respiratory tract
 +
File:Respiratory tract.jpg|conducting system bronchi to lungs
 
</gallery>
 
</gallery>
[[File:Stage14-22 lungs.jpg]] [[File:Stage_22_image_171.jpg|300px]]
+
{|
 +
| [[File:Lung_development_stage13-22.jpg]]
 +
| [[File:Stage_22_image_171.jpg|300px]]
 +
|-
 +
| [[Respiratory_System_-_Carnegie_Stage_13|Stage 13 (Week 4-5)]]
 +
| [[Respiratory_System_-_Carnegie_Stage_22|Stage 22 (Week 8)]]
 +
|}
  
* The lungs go through an embryonic and 4 distinct histological phases of development
+
[[File:Lung alveoli development cartoon.jpg|thumb|Lung alveoli development cartoon]]
 +
 
 +
* lung buds ( endoderm epithelial tubes) grow/push into mesenchyme covered with pleural cells (lung border)
 +
* generates a tree-like network by repeated:
 +
# elongation
 +
# terminal bifurcation
 +
# lateral budding
  
 
Growth initially of branched "conducting" system of bronchial tree, followed by later development of the "functional units" of the alveoli.
 
Growth initially of branched "conducting" system of bronchial tree, followed by later development of the "functional units" of the alveoli.
  
* '''embryonic''' week 4 - 5 (stage 14 above)
+
{| class="wikitable mw-collapsible mw-collapsed"
* '''pseudoglandular''' - week 5 - 17  (stage 22 above)
+
! Additional Information - Histology
'''canalicular''' - week 16 - 25
+
|-
* '''terminal sac''' - week 24 - 40
+
| This will be covered in detail in your associated SH Practical class.
* '''alveolar''' - late fetal - 8 years (Latin, ''alveus'' = cavity or hollow)
+
'''Respiratory Trachea'''
 +
 
 +
'''Mucosa''' - formed by epithelium and underlying lamina propria.
 +
* respiratory epithelium - (pseudostratified columnar and ciliated) ciliated cells, goblet cells, brush cells, endocrine cells, surfactant-producing cells (Clara cells), serous cells, basal cells, basement membrane.
 +
* lamina propria - loose connective tissue, many elastic fibres
  
===Lung morphogenesis===
+
'''Submucosa''' - connective tissue and submucosal glands
====Embryonic stage====
+
* submucosal glands (both serous and mucous parts)
[[File:Stage_13_image_070.jpg|600px]]
 
  
[[Movie_-_Gastrointestinal_Tract_3D_stage_13|Stage 13 movie]]
+
'''Cartilage'''
 +
* perichondrium
 +
* tracheal cartilage - hyaline cartilage, 16 to 20 C-shaped cartilages.
 +
* trachealis muscle - (smooth muscle) Not visible in this section, together with connective tissue fibres, join ends of the cartilages together.
  
* Lung buds ( endoderm epithelial tubes) grow/push into splanchnic mesenchyme covered with pleural cells (lung border)
+
'''Hyaline Cartilage Development'''
** '''embryonic tissue''' (adult tissue) organised inside to out
+
* forms from mesenchymal cells.
** '''endoderm''' (future respiratory epithelia) - '''splanchnic mesoderm''' (connective tissue, blood vessels, smooth muscle) - '''splanchnic mesothelium''' (visceral pleura) - pericardioperiotoneal canals (pleural cavity) - '''somatic mesothelium''' (parietal pleura) - '''somatic mesoderm''' (body wall CT, skeleton)
+
* precursor cells become rounded and form densely packed cellular masses, chondrification centres.
* generates a tree-like network by repeated:
+
* chondroblasts - (cartilage-forming cells) begin secreting the extracellular matrix components of cartilage.
 +
** extracellular matrix - ground substance (hyaluronan, chondroitin sulfates and keratan sulfate) and tropocollagen (polymerises into fine collagen fibres, not visible).
  
# elongation
+
<gallery>
# terminal bifurcation
+
File:Hyaline_cartilage_03.jpg|Trachea (overview HE)
# lateral budding
+
File:Hyaline_cartilage_04.jpg|Trachea (overview VG)
 +
File:Respiratory histology 05.jpg|Trachea (detail layers)
 +
File:Respiratory histology 06.jpg|Trachea (detail glands)
 +
</gallery>
  
===Pseudoglandular stage===
+
'''Bronchi Branching'''
[[File:Fetal lung histology.jpg|thumb|Fetal lung histology ([[:File:Fetal_lung_histology_01.jpg|large image]])]]
 
* week 5 - 17 (late embryonic, fetal)
 
* tubular branching of the human lung airways continues (16-25 generations of branching)
 
* 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, the more distal structures are lined with cuboidal epithelium.
 
  
===Canalicular stage===
+
main bronchi -> lobar bronchi -> segmental bronchi (supply lung bronchopulmonary segments) -> bronchi -> bronchioles (smaller than 1 mm) -> '''respiratory bronchioles'''.
  
* week 16 - 24 (fetal to end of second trimester)
+
* Trachea branches into 2 '''main bronchi''', with a histological structure similar to that of the trachea.
* Lung morphology changes dramatically
+
* branches are accompanied by branches of the pulmonary artery, nerves and lymph vessels
* differentiation of the pulmonary epithelium results in the formation of the future air-blood tissue barrier.
+
* surrounded by a layer of smooth muscle, which is located between the cartilage and epithelium.
* Surfactant synthesis and the canalization of the lung parenchyma by capillaries begin (week 17).
 
* future gas exchange regions can be distinguished from the future conducting airways of the lungs.
 
* 1 respiratory bronchiole gives rise to 3-6 alveolar ducts.
 
  
===Saccular stage===
+
'''Bronchioles'''
[[File:Lung alveoli development cartoon.jpg|thumb|Lung alveoli development cartoon]]
+
* transition from bronchi to bronchioles the epithelium changes to a '''ciliated columnar epithelium'''.
* week 24 to near term (fetal third trimester)
+
* Smooth muscle present, glands and cartilage are absent.
* 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.
 
  
===Alveolar stage===
+
'''Respiratory Bronchioles'''
[[File:Pig lung alveolarization.jpg|thumb|Fetal lung alveolarization]]
 
[[File:Alveolar-sac-01.jpg|Alveolar sac structure|600px]]
 
  
* Thyroid hormone required for differentiation and stimulate surfactant production.
+
* first structures that belong to the respiratory portion of the respiratory system.
====Alveolar type I cells====
+
* wall out-pouchings form alveoli (site of gas exchange)
* small alveolar cells, type I pneumocytes
+
* end in alveolar ducts
* very flat cells (thin as 0.05 µm)
+
* alveoli - duct or sac.
* form most of the surface of the alveolar walls
 
* may contribute epithelium on both faces of the alveolar wall
 
  
====Alveolar type II cells====
+
<gallery>
* large alveolar cells, type II pneumocytes  
+
File:Respiratory_histology_01.jpg|Bronchiole
* irregular to cuboidal shaped cells
+
File:Respiratory histology 10.jpg|Lung Elastin
* contain large number of granules called lamellar bodies, these are the precursors to pulmonary surfactant (phospholipid mixture).
+
File:Respiratory histology 08.jpg|labeled lung
 +
</gallery>
 +
{|
 +
|-
 +
| valign=top width=350px|'''Alveolar type I cells'''
 +
* small alveolar cells or type I pneumocytes
 +
* are extremely flattened (the cell may be as thin as 0.05 µm)
 +
* form the bulk (95%) of the surface of the alveolar walls.
 +
* The shape of the cells is very complex, and they may actually form part of the epithelium on both faces of the alveolar wall.
 +
 +
| valign=top width=350px|'''Alveolar type II cells'''
 +
* large alveolar cells or type II pneumocytes
 +
* about as many type II cells as type I cells (cell shape accounts for small contribution to alveolar area).
 +
* irregularly (sometimes cuboidal) shaped.
 +
* form small bulges on the alveolar walls.
 +
* contain are large number of granules called cytosomes (or multilamellar bodies)
 +
** consist of precursors to pulmonary surfactant (mixture of phospholipids that keep surface tension in the alveoli low).  
 +
|}
  
* end month 6 alveolar cells type 2 appear and begin to secrete surfactant - premature babies have difficulties associated with insufficient surfactant.
+
<gallery>
 +
File:Respiratory_histology_02.jpg|Alveolar Duct
 +
File:Respiratory_histology_03.jpg|Alveoli
 +
File:Respiratory histology 04.jpg|Alveoli Elastin
 +
</gallery>
  
====Alveolar macrophages====
+
{{Respiratory Histology}}
* remove particulate matter that enters the alveoli with inspired air
 
* migrate over alveolar epithelium and phagocytose particulate matter
 
  
===Fetal lung volume===
+
|}
Each lung volume as determined by ultrasound and matched to gestational age (PMID: 16388511)
+
===Fetal Lung Volume===
* 12-13 weeks 0.05 mL
+
Each human lung volume as determined by ultrasound and matched to gestational age{{#pmid:16388511|PMID16388511}}
* 19-22 weeks 0.5 mL
+
{|
* 29-32 weeks 1.9 mL
+
|
 +
{|
 +
|-bgcolor="CEDFF2"
 +
| Weeks (gestational)
 +
| Volume (ml)
 +
|-
 +
| 12 to 13
 +
| 0.05
 +
|-bgcolor="F5FAFF"
 +
| 19 to 22
 +
| 0.5
 +
|-
 +
| 29 to 32
 +
| 1.9
 +
|}
 +
| [[File:Lung volume graph 01.jpg|200px]]
 +
|}
  
 
== Pleural Cavity ==
 
== Pleural Cavity ==
 
[[File:Gray0965.jpg|thumb|pleura]]
 
[[File:Gray0965.jpg|thumb|pleura]]
 
[[File:Gray0968.jpg|thumb|pleura]]
 
[[File:Gray0968.jpg|thumb|pleura]]
* The anatomical body cavity in which the lungs develop and lie.  
+
* 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.  
+
* 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
+
* 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
+
** 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.
+
* '''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.
  
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'''.
 +
* filled with pleural fluid produced by parietal pleura and reabsorbed by parietal pleural lymphatics.{{#pmid:9032518|PMID9032518}}
 +
* excess fluid - pleural effusion.
  
 +
==Diaphragm==
 +
Adult Diaphragm.
  
===Pleura===
+
[[File:Gray0391.jpg|400px|adult diaphragm]]
* serous membrane covers the surface of the lung and the spaces between the lobes
+
 
* arranged as a closed invaginated sac
+
* Not respiratory tract but musculoskeletal development, there are '''5 embryonic elements''' that contribute to the diaphragm.
* two layers (pulmonary, parietal) continuous with each other, the potential space between them is the '''pleural cavity'''
+
* Innervation of the human diaphragm is by the '''phrenic nerves'''
  
==Diaphragm==
 
Not respiratory tract but musculoskeletal development, there are  5 elements that contribute to the diaphragm.
 
 
{|
 
{|
 
| [[File:Diaphragm components.jpg|300px|Components of the diaphragm]]
 
| [[File:Diaphragm components.jpg|300px|Components of the diaphragm]]
Line 237: Line 503:
 
# pleuroperitoneal membranes- connective tissue around central tendon
 
# pleuroperitoneal membranes- connective tissue around central tendon
 
|}
 
|}
[[File:Gray804.gif|thumb|Adult Cervical Plexus (phrenic nerve shown lower right)]]
+
[[File:Gray0804.jpg|thumb|Adult Cervical Plexus (phrenic nerve shown lower right)]]
[[File:Adult diaphragm.jpg|300px|adult diaphragm]]
+
 
 +
 
 +
 
 +
*Phrenic Nerves - arising from the same segmental levels as the diaphragm skeletal muscles, 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).
  
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 containing motor neurons for the diaphragm and sensory nerves for other abdominal structures (mediastinum, pleura, liver, gall bladder).
+
'''Bochdalek hernia''' -  most common on the posterior left side (85%). 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.
  
 
==Pulmonary Circulation==  
 
==Pulmonary Circulation==  
[[File:Pulmonary circulation cartoon.jpg|thumb|300px|Pulmonary circulation]]
+
 
[[File:Gray0975.jpg|thumb|alveoli and blood vessels]]
 
 
* the pulmonary system not "functional" until after birth  
 
* the pulmonary system not "functional" until after birth  
* pulmonary arteries - (deoxygenated blood to lung) 6th aortic arch arteries
+
* pulmonary arteries - 6th aortic arch arteries
* pulmonary veins - (oxygenated blood from lung) are incorporated into the left atrium wall  
+
* pulmonary veins - are incorporated into the left atrium wall  
 
* bronchial arteries - branches from dorsal aorta
 
* bronchial arteries - branches from dorsal aorta
  
==Fetal Respiratory Movements==
+
[[File:Pulmonary circulation cartoon.jpg|400px]]
 +
 
 +
Pulmonary circulation
 +
 
 +
==Fetal==
 +
===Fetal Respiratory Movements===
 
* Fetal respiratory movements (FRM) or Fetal breathing movements (FBM) are regular muscular contrations occurring in the third trimester.  
 
* 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 (and amniotic fluid are thought to have a role in lung maturation)
+
* preparing the respiratory muscular system for neonatal function.
thought to also have a role in late lung development.
+
may also have a role in late lung development.
 +
 
  
==The First Breath==
+
 
[[File:Alveolar-sac-01.jpg|thumb|Alveolar sac structure]]
+
==Postnatal==
 +
===The First Breath===
 +
{|
 +
|
 
* The respiratory system does not carry out its physiological function (gas exchange) prenatally and remain entirely fluid-filled until birth.  
 
* 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".
 
* 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 lung epithelia has to now rapidly change from its prenatal secretory function to that of fluid absorbtion.  
  
===Exchange of Fluid for Air===
+
 
 +
The exchange of lung fluid for air leads to:
 
* fall in pulmonary vascular resistance
 
* fall in pulmonary vascular resistance
 
* increase in pulmonary blood flow
 
* increase in pulmonary blood flow
Line 269: Line 549:
 
* blood fills the alveolar capillaries
 
* 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).
 
[[File:Neonatal rib orientation.jpg|thumb|Neonatal rib orientation]]
 
* Respiratory Rate is higher than adult (30 breaths/minute).
 
===Rib Orientation===
 
* Infant rib is virtually horizontal, allowing only diaphragmatic breathing
 
* Adult rib orientation is oblique (both anterior and lateral views), allows for pump-handle and bucket handle types of inspiration.
 
  
== Respiratory Tract Histology==
+
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).
<gallery>
+
| [[File:Alveolar-sac-01.jpg|400px]]
File:Respiratory_histology_05.jpg|Trachea
+
 
File:Respiratory_histology_06.jpg|Trachea
+
Alveolar sac structure
File:Respiratory_histology_01.jpg|Bronchiole
+
|}
File:Respiratory histology 09.jpg|Bronchiole ciliated simple columnar epithelium
+
===Alveoli===
File:Respiratory histology 07.jpg|Lung structure
+
{|
File:Respiratory_histology_02.jpg|Alveoli and Duct
+
|
File:Respiratory_histology_03.jpg|Alveoli
+
* At birth about 15% of adult alveoli number have formed
File:Respiratory_histology_04.jpg|Alveoli elastin
+
** 20 - 50 million to in the adult about 300 million.
</gallery>
+
* remaining subdivisions develop in the first few postnatal years
 +
| [[File:Postnatal_alveoli_number.jpg|400px]]
 +
 
 +
Human 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
 +
{|
 +
|-bgcolor="CEDFF2"
 +
| width= "300px"|'''Age'''
 +
| width= "200px"|'''Rate''' (breaths/minute)
 +
|-
 +
| Infant (birth - 1 year)
 +
| 30 - 60
 +
|- bgcolor="F5FAFF"
 +
| Toddler (1 - 3 years)
 +
| 24 - 40
 +
|-
 +
| Preschool (3 - 6 years)
 +
| 22 - 34
 +
|-bgcolor="F5FAFF"
 +
| School age (6 - 12 years)
 +
| 18 - 30
 +
|-
 +
| Adolescent (12 - 18 years)
 +
| 12 - 16
 +
|-bgcolor="F5FAFF"
 +
|
 +
|}
  
 +
===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.
 +
| [[File:Neonatal rib orientation.jpg|300px]]
  
:'''Histology Links:''' [http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Respiratory/respir.htm Blue Histology] | [http://vslides.unsw.edu.au/VirtualSlideV2.nsf/id/F51ED7 UNSW Virtual Slides] | [http://www.path.uiowa.edu/cgi-bin-pub/vs/fpx_browse.cgi?cat=o_lung&div=nlm UIOWA Virtual Slidebox]
+
Rib orientation
 +
|}
  
 
== Respiratory Tract Abnormalities ==
 
== Respiratory Tract Abnormalities ==
[[File:Respiratory tract.jpg|thumb|conducting system bronchi to lungs]]
+
[[File:Human congenital diaphragmatic hernia.jpg|thumb|Congenital diaphragmatic hernia]]
 +
[[File:Lung_Azygos_Lobe_02.jpg|thumb|Lung Azygos Lobe]]
 +
[[File:Preterm delivery and lung development.jpg|thumb|Preterm Birth]]
 
[[Respiratory System - Abnormalities]]
 
[[Respiratory System - Abnormalities]]
===Tracheoesophageal Fistula ===
 
* Tracheo-Oesophageal Fistula, Oesophageal Atresia - Oesophageal Atresia with or without tracheo-oesophageal [[F#fistula|fistula]]
 
** '''Fistula''' - an abnormal communication between 2 structures (organs, vessels, cavities) that do not normally connect.
 
  
===Lobar Emphysema (Overinflated Lung)===
+
* '''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.
# There is an overinflated left upper lobe
+
 
# There is a collapsed lower lobe
+
* '''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 [http://www.nlm.nih.gov/MEDLINEPLUS/ency/article/001563.htm medline plus] | [http://www.medscape.com/article/976034-overview eMedicine]
# The left lung is herniating across the mediastinum
+
 
 +
* '''Tracheoesophageal Fistula''' - Tracheo-Oesophageal Fistula, Oesophageal Atresia - Oesophageal Atresia with or without tracheo-oesophageal [[F#fistula|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. [[Respiratory_System_-_Abnormalities#Congenital_Diaphragmatic_Hernia|Congenital Diaphragmatic Hernia]] | [http://www.ncbi.nlm.nih.gov/books/NBK1359 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) historic terminology, 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.
 +
 
 +
* '''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)
 +
 
 +
* '''Vascular development''' - During both the prenatal and postnatal development, impaired angiogenesis from a number of causes can decrease alveolarization of the lung. (decreased VEGF expression, increased oxygen tension, inflammatory cytokines, other adverse stimuli)
 +
 
 +
===Environmental Factors===
 +
The lung is most sensitive to environmental effects given the long timecourse of development, including postnatal, multi-system origins, immune interactions, and our growing understanding of the effects of the prenatal environment on adult health ([[Abnormal_Development_-_Developmental_Origins_of_Health_and_Disease|DOHAD]]). Below are some recent reviews of related topics.(not part of today's lecture presentation)
 +
 
 +
* [[Abnormal Development - Fetal Alcohol Syndrome|Maternal alcohol]]{{#pmid:27613232|PMID27613232}}
 +
* Maternal obesity{{#pmid:27818069|PMID27818069}}
 +
* Maternal diabetes{{#pmid:27665512|PMID27665512}}
 +
* Maternal smoking{{#pmid:27639458|PMID27639458}}
 +
* Chronic hypoxaemia{{#pmid:27692868|PMID27692868}}
 +
* Environmental chemicals{{#pmid:20444669|PMID20444669}}
 +
==Respiratory Terms==
 +
{{Respiratory terms}}
 +
 
 +
==Additional Information==
 +
{{Med Prac additional Information}}
 +
 
 +
{| class="wikitable mw-collapsible mw-collapsed"
 +
! Developing Rat Lung (3D view) &nbsp;
 +
|-
 +
| From transitional bronchiole to alveolus!
 +
 
 +
<html5media height="500" width="856">File:Rat respiratory 01.mp4</html5media>
 +
|-
 +
| The flight starts by entering a transitional bronchiole.
 +
 
 +
Domes of Club cell are visible on the surface of the bronchiole. Turning left an alveolar duct is entered. Various alveoli and the entrance of few alveolar ducts are visible. Shortly before the end of first alveolar duct, the fight turns left again and flies down another alveolar duct. After a short distance it ends in front of an alveolus which is subdivided by a low ridge representing a still forming new alveolar septum. Rat lung at postnatal day 36.
 +
 
 +
Surface rendering of a sample scanned by SRXTM for Schittny et al. (Schittny et al. 2008) using the software Imaris 4.1 (Bitplane, Zürich, Switzerland). Because the magnification is changing during the flight a scale bar could not be easily shown. However, the entrance of the bronchiole has a diameter of ~100 µm  (text from suppl. information)
 +
 
 +
{{#pmid:30390117}}
 +
 
 +
 
 +
Note - {{mouse}} and {{rat}} the acini and the ventilatory units are the same entity because they do not possess any respiratory bronchioles. The {{mouse}} model (C57BL/6J) completely lacks respiratory breathing movements seen in the human fetus.
 +
{{#pmid:18980217|PMID18980217}}
 +
|}
 +
 
 +
[[Respiratory Quiz]]
 +
 
 +
 
 +
==Lung Development - Respiratory Health and Disease==
 +
{{#pmid:30111617}}
 +
 
 +
{{#pmid:30021997}}
 +
 
 +
{{#pmid:30016982}}
 +
 
 +
{{#pmid:24429276}}
  
===Congenital Diaphragmatic Hernia===
+
{{#pmid:12615030}}
* 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.
 
  
:'''Links:''' [http://www.ncbi.nlm.nih.gov/books/NBK1359 GeneReviews]
 
  
===Azygos Lobe===
+
[[File:Gray0971.jpg|thumb|adult lungs]]
[[File:Lung_Azygos_Lobe_02.jpg|thumb|Lung 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===
+
{| class="wikitable mw-collapsible mw-collapsed"
* Laryngeal abnormality due to embryonic (week 10) incomplete recanalization of the laryngotracheal tube during the fetal period.  
+
!  Grays - Respiratory Images
* Rare abnormality occuring mainly at the level of the vocal folds (glottis).
+
|-
 +
|
 +
<gallery>
 +
File:Gray0947.jpg|947 The head and neck human embryo thirty-two days seen from the ventral surface.
 +
File:Gray0948.jpg|948 Lung buds from a human embryo of about four weeks, showing commencing lobulations.
 +
File:Gray0949.jpg|949 Lungs of a human embryo more advanced in development than week 4.
 +
File:Gray0950.jpg|950 Cartilages of the larynx
 +
File:Gray0950 epiglottis cartilage.jpg|950 epiglottis  cartilage
 +
File:Gray0950 thyroid cartilage.jpg|950 thyroid cartilage
 +
File:Gray0950 cricoid cartilage.jpg|950 cricoid cartilage
 +
File:Gray0950 arytenoid cartilage.jpg|950 arytenoid cartilage
 +
File:Gray0951.jpg|951 Ligaments of the larynx (anterior view)
 +
File:Gray0952.jpg|952 Ligaments of the larynx (posterior view)
 +
File:Gray0953.jpg|953 Larynx and upper part of the trachea
 +
File:Gray0954.jpg|954
 +
File:Gray0955.jpg|955 Larynx entrance
 +
File:Gray0956.jpg|956
 +
File:Gray0957.jpg|957
 +
File:Gray0958.jpg|958
 +
File:Gray0959.jpg|959
 +
File:Gray0960.jpg|960
 +
File:Gray0961.jpg|961 Cartilages of larynx, trachea, and bronchi (front view)
 +
File:Gray0962.jpg|962 Bronchi and bronchioles
 +
File:Gray0963.jpg|963
 +
File:Gray0964.jpg|964
 +
File:Gray0965.jpg|965
 +
File:Gray0966.jpg|966 Lateral view of thorax, showing the relations of the pleuræ and lungs to the chest wall. Pleura in blue; lungs in purple.
 +
File:Gray0967.jpg|967 Transverse section through the upper margin of the second thoracic vertebra.
 +
File:Gray0968.jpg|968
 +
File:Gray0969.jpg|969
 +
File:Gray0970.jpg|970 Front view of heart and lungs
 +
File:Gray0971.jpg|971 Adult lungs
 +
File:Gray0974.jpg|974 Lung secondary lobule
 +
File:Lung_secondary_lobule_01.jpg|974 relabeled version
 +
File:Gray0975.jpg|975 Lung primary lobule
 +
File:Lung_primary_lobule_01.jpg|975 relabeled version
 +
File:Gray0976.jpg|976 Pig embryo lung
 +
</gallery>
 +
|}
  
===Meconium Aspiration Syndrome===
+
{| class="wikitable mw-collapsible mw-collapsed"
 +
!  Respiratory Histology &nbsp;
 +
|-
 +
|
 +
Histology will be covered in more detail in your associated practical class.
  
(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.
+
===Fetal Histology===
 +
<gallery>
 +
File:Fetal lung histology 02.jpg|Hyaline cartilage
 +
File:Fetal lung histology.jpg|late canalicular
 +
File:Fetal lung histology 01.jpg|unlabeled late canalicular
 +
</gallery>
  
===Newborn Respiratory Distress Syndrome===
+
{{Fetal_Respiratory_Histology}}
* Hyaline Membrane Disease (membrane-like substance from damaged pulmonary cells)
+
 
* absence of surfactant, if prolonged can be irreversible
+
===Adult Histology===
* intrauterine asphyxia, prematurity and maternal diabetes
+
<gallery>
 +
File:Respiratory histology 13.jpg|Olfactory Epithelium
 +
File:Respiratory histology 14.jpg|Olfactory Epithelium
 +
File:Respiratory histology 11.jpg|Respiratory Epithelium
 +
File:Respiratory histology 12.jpg|Respiratory Epithelium
 +
File:Respiratory histology 05.jpg|Trachea 1
 +
File:Respiratory histology 06.jpg|Trachea 2
 +
File:Respiratory_histology_01.jpg|Bronchiole
 +
File:Respiratory histology 10.jpg|Lung Elastin
 +
File:Respiratory histology 08.jpg|labeled lung
 +
File:Respiratory_histology_02.jpg|Alveolar Duct
 +
File:Respiratory_histology_03.jpg|Alveoli
 +
File:Respiratory histology 04.jpg|Alveoli Elastin
 +
</gallery>
 +
 
 +
{{Respiratory_Histology}}
 +
|}
  
:'''Links:''' [http://www.nlm.nih.gov/MEDLINEPLUS/ency/article/001563.htm medline plus] | [http://www.medscape.com/article/976034-overview eMedicine]
+
==References==
 +
<references/>
  
===Bronchopulmonary Dysplasia===
 
* A chronic lung disease which can occur following premature birth.
 
* The definition of bronchopulmonary dysplasia (BPD) has in recent years changed from a severe lung injury and associated repair, to more of a disruption of lung development.
 
  
==Terms==
 
* '''antenatal''' before birth.
 
* '''alveoli number at birth''' -  from 20 - 50 million and eventually in the adult 300 million.
 
* '''Bronchopulmonary dysplasia''' - (BPD) the most common serious sequela of premature birth.
 
* '''Bronchiolitis''' - is a viral infection of the lower respiratory tract and most common lower respiratory tract infection in infants. Respiratory syncytial virus (RSV) is responsible for 70 percent of all cases overall and Parainfluenza, adenovirus and influenza account for most of the remaining cases. (HSTAT Management of Bronchiolitis in Infants and Children)
 
* '''Chronic obstructive pulmonary disease''' (COPD) causes include smoking (85–90 percent of all cases), genetic factors (alpha-1 antitrypsin deficiency), passive smoking (children), occupational exposures, air pollution, and hyperresponsive airways. (HSTAT Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease)
 
* '''Clara cells''' non-ciliated cell found in the small airways (bronchioles) consisting of ciliated simple epithelium, these cells secrete glycosaminoglycans (Clara cell secretory protein, CCSP) to protect the bronchiole lining.
 
* '''Congenital Diaphragmatic Hernia''' (CDH) disorder with an incidence of 1 in 2500 live births.
 
* '''fetal breathing-like movements''' (FBMs) or Fetal respiratory movements are thought to be regular muscular contrations occurring in the third trimester, preparing the respiratory muscular system for neonatal function and to have a role in late lung development.
 
* '''glucocorticoid treatment''' - antenatal therapy to promote the maturation of the human fetal lung. Given as a synthetic glucocorticoid between 24 and 32 weeks of pregnancy to promote lung maturation in fetuses at risk of preterm delivery.
 
* '''lamellar bodies''' the storage form of surfactant in type II alveolar cells, seen as centrically layered "packages" of phospholipid. A count of lamellar bodies can be used as an assay for measuring fetal lung maturity.
 
* '''maternal diabetes''' if not controlled in pregnancy may delay fetal pulmonary maturation.
 
* '''Persistent Pulmonary Hypertension of the Newborn''' (PPHN) serious newborn condition due to due to the failure of closure one of the prenatal circulatory shunts, the ductus arteriosus. Occurs in about 1-2 newborns per 1000 live births and results in hypoxemia. (More? Respiratory Development - Birth)
 
* '''Pharyngitis''' inflammation of the pharynx involving lymphoid tissues of the posterior pharynx and lateral pharyngeal bands.
 
* '''pneumocyte''' or alveolar type I and type II cells.
 
* '''pulmonary hypoplasia''' can be due to anencephaly, renal hypoplasia or abnormalities of the thoracic cage
 
* '''pulmonary neuroendocrine cells''' (PNEC) single or innervated clusters of cells (neuroepithelial bodies) that line the airway epithelium, thought to have a role in regulating fetal lung growth and differentiation. At birth may also act as airway oxygen sensors involved in newborn adaptation. These cells synthesis and release amine (serotonin, 5-HT) and a several neuropeptides (bombesin).
 
* '''Respiratory distress syndrome''' (RDS) due to a surfactant deficiency at birth, particulary in preterm birth.
 
* '''secondary alveolar septa''' formed during the alveolar stage and are formed by projections of connective tissue and a double capillary loop.
 
*''' surfactant''' produced by alveolar type II cells is a mixture of lipids and proteins that both maintains alveolar integrity and plays a role in the control of host defense and inflammation in the lung.
 
* '''Surfactant therapy''' ([http://aappolicy.aappublications.org/cgi/content/full/pediatrics;121/2/419 American Academy of Pediatrics Policy] | [http://www.cps.ca/english/statements/fn/fn05-01.htm Canadian Paediatric Society Recommendations])
 
*''' thyroid hormone''' involved in the regulation of fetal lung development.
 
* '''vascular endothelial growth factor''' (VEGF) a secreted growth factor acting through receptors on endothelial cells to regulate vasculogenesis through their development, growth and function.
 
 
{{Glossary}}
 
{{Glossary}}
  
 
{{Footer}}
 
{{Footer}}
  
[[Category:Endoderm]] [[Category:Respiratory]]
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[[Category:Endoderm]] [[Category:Respiratory]][[Category:2019]]

Latest revision as of 13:19, 28 February 2019

Embryology - 14 Nov 2019    Facebook link Pinterest link Twitter link  Expand to Translate  
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Introduction

Fetal Pharynx (week 12)
SHsmall.jpg 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. Mark Hill.jpg


Current research suggests that both genetic and the developmental environment (fetal and postnatal) can influence the growth, differentiation and function of the respiratory system.
Lower respiratory tract Respiratory tree
Bronchi lungs.jpg
Respiratory tract.jpg

2019 Respiratory Development Lecture PDF

Lecture Archive  
2018 PDF | 2017 | 2017 PDF | 2016 | 2016 PDF | 2015 | 2015 PDF | 2014 | Lecture 2014 PDF | 2013 PDF | 2013 | 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.

Aim

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

Textbooks  
Logo.png Hill, M.A. (2019). UNSW Embryology (19th ed.) Retrieved November 14, 2019, from https://embryology.med.unsw.edu.au
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  
1902 The Nasal Cavities and Olfactory Structures | 1906 Lung | 1912 Upper Respiratory Tract | 1912 Respiratory | 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
The Developing Human, 10th edn.jpg Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2015). The developing human: clinically oriented embryology (10th ed.). Philadelphia: Saunders.
Larsen's human embryology 5th ed.jpg Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.
Additional Textbooks
Review article
  • 2017 [www.lungmap.net LungMAP]: The Molecular Atlas of Lung Development Program.[1]
  • 2017 Development of the lung.[2]
  • 2017 Developmental pathways in lung regeneration.[3]
  • 2017 In utero alcohol effects on foetal, neonatal and childhood lung disease.[4]
  • 2014 Lung development: orchestrating the generation and regeneration of a complex organ.[5]

Key Concepts

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

Respiratory Functional Unit

Alveolus

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

Respiratory histology 03.jpg Alveolar-sac-01.jpg
Alveolus histology Alveolus structure

Inter-Alveolar Septum[6]

Human lung inter-alveolar septum em01.jpg

Septum containing Type I (AEC1) and type II (AEC2) alveolar epithelial cell, alveolar lumen (Alv), capillary lumen (Cap), capillary endothelial cell (Endo ). Lamellar bodies (LB) in type II cell. Arrowheads mark tight junctions between type II and type I cell. Collagen fibrils (col) are present in the interstitium. Transmission electron microscopy. Scale bar 2 µm


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
  • size - up to 2.5 cm across.
  • connective tissue - bounded by fibrous (interlobular) septa and containing finer internal septa.
  • lobule contains a up to 12 acini and 30 - 50 primary lobules.
  • blood supply - pulmonary artery branch
  • blood drainage - pulmonary veins located at lobule periphery leave though the interlobular septa.
  • lymphatics - arterial and interlobular septa associated (drain to subpleural plexus).

Developmental Overview

Lung alveoli development cartoon.jpg

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.

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 Stages - timing, airway and vascular development[7]
Human lung stages 01.jpg

Embryonic

Week 4 to 5 - lung buds originate as an outgrowth from the ventral wall of the foregut where lobar division occurs.

Endoderm development cartoon
Stage11 bf9.jpg Stage11 sem4.jpg
Stomodeum (Week 4, stage 11, GA week 6) Buccopharyngeal membrane (Week 4, stage 11, GA week 6)

Week 5 Respiratory Development

(Week 5, stage 14, GA week 7)

  • 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.

Stage 13 - Trachea and Lung buds (MRI sagittal sections)

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.
  • Pulmonary neuroendocrine cells (PNECs) - develop in late embryonic to early fetal period, later in mid-fetal period clusters of these cells form [neuroepithelial bodies (NEBs) in airway epithelium. May stimulate mitosis to increase branching, secrete 2 peptides - gastrin-releasing peptide (GRP) and calcitonin gene related peptide (CGRP).


ME54 001.jpg

Week 8

Fetal lung histology.jpg

Fetal lung histology

(This is what a gland looks like.)


Pseudoglandular and Canalicular Stages  
Canalicular phase of bronchus can be mixed with the pseudoglandular phase.

Pulmonary Pleura - pseudoglandular and canalicular stages 02.jpg

Human Lung showing a mix of pseudoglandular and canalicular stages[8]

Canalicular stage

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

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

Secondary septum
  • late fetal to 8 years.
  • Secondary septum
  • Expansion of gas exchange alveoli, vascular beds (capillaries), lymphatics and innervation.
  • Postnatal lung, with alveoli forming.
Postnatal alveoli number.jpg

Upper Respiratory Tract

Foregut cartoon
Pharynx

Foregut Development - 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.

Pharynx
  • part of foregut development (Oral cavity, Pharynx (esophagus, trachea), Respiratory tract, Stomach)
  • anatomically the nose, nasal cavity and the pharynx
  • pharynx forms a major arched cavity within the pharyngeal arches (MH - pharyngeal arches will be described in BGD head development lecture).
  • palate - development for mammals, allows breathing while feeding.

Note - Specialised olfactory epithelium for smell, a small region located in roof of nasal cavity.

Respiratory histology 11.jpg Respiratory epithelium
  • pseudo-stratified
  • ciliated cells
  • goblet cells
  • basal cells

Respiratory epithelium cells cartoon.jpg

Respiratory epithelium development


Additional Information - Histology
This will be covered in detail in your associated SH Practical class.
Olfactory epithelium
  • Olfactory cells
  • Sustentacular cells - located mainly in the superficial cell layer of the epithelium (difficult to distinguish from olfactory cells).
  • Basal cells - identified by their location in the epithelium.

Epithelium

  • Cilia are not visible
  • goblet cells are absent from the olfactory epithelium.

Lamina Propria

  • olfactory axon bundles (lightly stained, rounded areas) connected to olfactory cells.
  • Bowman's glands - (small mucous glands, olfactory glands) function to moisturise the epithelium.
Nasal Olfactory Histology: overview image | detail image | Smell Development | Histology | Histology Stains


Respiratory epithelium
  • goblet cells
  • ciliated cells
  • basal cells

Lamina propria

  • connective tissue
  • cavernous sinusoids - large spaces (empty or filled with red blood cells)
  • glandular tissue - mucous glands (green) and muco-serous glands (brownish-green)

Bone

  • Lamellae and osteocytes in lacunae.
  • Haversian systems are rare or absent.
Nasal Respiratory Histology: overview image | detail image | Histology | Histology Stains
Respiratory Histology: Bronchiole | Alveolar Duct | Alveoli | EM Alveoli septum | Alveoli Elastin | Trachea 1 | Trachea 2 | labeled lung | unlabeled lung | Respiratory Bronchiole | Lung Reticular Fibres | Nasal Inferior Concha | Nasal Respiratory Epithelium | Olfactory Region overview | Olfactory Region Epithelium | Histology Stains


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
  • 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.

Additional Information - Histology
This will be covered in detail in your associated SH Practical class.

Respiratory Trachea

Mucosa - formed by epithelium and underlying lamina propria.

  • respiratory epithelium - (pseudostratified columnar and ciliated) ciliated cells, goblet cells, brush cells, endocrine cells, surfactant-producing cells (Clara cells), serous cells, basal cells, basement membrane.
  • lamina propria - loose connective tissue, many elastic fibres

Submucosa - connective tissue and submucosal glands

  • submucosal glands (both serous and mucous parts)

Cartilage

  • perichondrium
  • tracheal cartilage - hyaline cartilage, 16 to 20 C-shaped cartilages.
  • trachealis muscle - (smooth muscle) Not visible in this section, together with connective tissue fibres, join ends of the cartilages together.

Hyaline Cartilage Development

  • forms from mesenchymal cells.
  • precursor cells become rounded and form densely packed cellular masses, chondrification centres.
  • chondroblasts - (cartilage-forming cells) begin secreting the extracellular matrix components of cartilage.
    • extracellular matrix - ground substance (hyaluronan, chondroitin sulfates and keratan sulfate) and tropocollagen (polymerises into fine collagen fibres, not visible).

Bronchi Branching

main bronchi -> lobar bronchi -> segmental bronchi (supply lung bronchopulmonary segments) -> bronchi -> bronchioles (smaller than 1 mm) -> respiratory bronchioles.

  • Trachea branches into 2 main bronchi, with a histological structure similar to that of the trachea.
  • branches are accompanied by branches of the pulmonary artery, nerves and lymph vessels
  • surrounded by a layer of smooth muscle, which is located between the cartilage and epithelium.

Bronchioles

  • transition from bronchi to bronchioles the epithelium changes to a ciliated columnar epithelium.
  • Smooth muscle present, glands and cartilage are absent.

Respiratory Bronchioles

  • first structures that belong to the respiratory portion of the respiratory system.
  • wall out-pouchings form alveoli (site of gas exchange)
  • end in alveolar ducts
  • alveoli - duct or sac.
Alveolar type I cells
  • small alveolar cells or type I pneumocytes
  • are extremely flattened (the cell may be as thin as 0.05 µm)
  • form the bulk (95%) of the surface of the alveolar walls.
  • The shape of the cells is very complex, and they may actually form part of the epithelium on both faces of the alveolar wall.
Alveolar type II cells
  • large alveolar cells or type II pneumocytes
  • about as many type II cells as type I cells (cell shape accounts for small contribution to alveolar area).
  • irregularly (sometimes cuboidal) shaped.
  • form small bulges on the alveolar walls.
  • contain are large number of granules called cytosomes (or multilamellar bodies)
    • consist of precursors to pulmonary surfactant (mixture of phospholipids that keep surface tension in the alveoli low).
Respiratory Histology: Bronchiole | Alveolar Duct | Alveoli | EM Alveoli septum | Alveoli Elastin | Trachea 1 | Trachea 2 | labeled lung | unlabeled lung | Respiratory Bronchiole | Lung Reticular Fibres | Nasal Inferior Concha | Nasal Respiratory Epithelium | Olfactory Region overview | Olfactory Region Epithelium | Histology Stains


Fetal Lung Volume

Each human lung volume as determined by ultrasound and matched to gestational age[9]

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

pleura
pleura
  • 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.

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.
  • filled with pleural fluid produced by parietal pleura and reabsorbed by parietal pleural lymphatics.[10]
  • excess fluid - pleural effusion.

Diaphragm

Adult Diaphragm.

adult diaphragm

  • Not respiratory tract but musculoskeletal development, there are 5 embryonic elements that contribute to the diaphragm.
  • Innervation of the human diaphragm is by the phrenic nerves
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)


  • Phrenic Nerves - arising from the same segmental levels as the diaphragm skeletal muscles, 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).


Bochdalek hernia - most common on the posterior left side (85%). 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.

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

Pulmonary circulation cartoon.jpg

Pulmonary circulation

Fetal

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.


Postnatal

The First Breath

  • 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).

Alveolar-sac-01.jpg

Alveolar sac structure

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
Postnatal alveoli number.jpg

Human 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.
Neonatal rib orientation.jpg

Rib orientation

Respiratory Tract Abnormalities

Congenital diaphragmatic hernia
Lung Azygos Lobe
Preterm Birth

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. 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) historic terminology, 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.
  • 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)
  • Vascular development - During both the prenatal and postnatal development, impaired angiogenesis from a number of causes can decrease alveolarization of the lung. (decreased VEGF expression, increased oxygen tension, inflammatory cytokines, other adverse stimuli)

Environmental Factors

The lung is most sensitive to environmental effects given the long timecourse of development, including postnatal, multi-system origins, immune interactions, and our growing understanding of the effects of the prenatal environment on adult health (DOHAD). Below are some recent reviews of related topics.(not part of today's lecture presentation)

Respiratory Terms

Respiratory Terms (expand to view) 
  • adenovirus - A Class I virus containing a single double-stranded DNA (dsDNA), which can cause infections in the upper respiratory tract in many animals. (More? viral infection)
  • alveolar duct - Anatomical short region lying between the end of the respiratory bronchioles and the final alveolar sacs. Term is also used in the mammary gland, to describe the smallest of the intralobular ducts into which the secretory alveoli open.
  • alveolar sac - (alveolus), Latin alveolus = little cavity) Anatomical and functional end of the mammalian lung respiratory tree where gas exchange occurs. In humans, during lung development these are the last features to form from 7 months onwards.
  • alveolar - Term used in relation to the alveoli of the lungs. The final functional sac of the respiratory tree where gas exchange occurs between the alveolar space and the pulmonary capillaries.
  • alveolar stage - Term used to describe lung development, the final histological/developmental stage (Pseudoglandular, Fetal Canalicular, Terminal sac, Alveolar). This stage occurs from late fetal/neonate with alveoli formation, the final functional sac of the respiratory tree exists, where gas exchange occurs between the alveolar space and the pulmonary capillaries. (embryonic stage - pseudoglandular stage - canalicular stage - saccular stage - alveolar stage)
  • alveolus - (alveolar sacs, plural alveoli, Latin alveolus = little cavity) Anatomical and functional end of the mammalian lung respiratory tree where gas exchange occurs. In humans, during lung development these are the last features to form from 7 months onwards. The acinus starts approximately 3 to 4 generations proximal of the bronchioalveolar duct junction and ends about 4 generations of alveolar ducts distal of the bronchioalveolar duct junction.
  • angiogenesis - vascular growth by direct extension from pre-existing blood vessels. (see also vasculogenesis).
  • apgar - Non-invasive clinical test designed by Dr Virginia Apgar (1953) carried out immediately on newborn. The name is also an acronym for: Activity (Muscle Tone), Pulse, Grimace (Reflex Irritability), Appearance (Skin Color), Respiration. A score is given for each sign at one minute and five minutes after the birth. (More? Apgar test)
  • apnea - Respiratory term meaning the cessation of breathing.
  • assisted ventilation - Clinical term referring to newborn (perinatal) respiration assistance required immediately following delivery, the infant given minimal breaths for any duration with bag and mask or bag and endotracheal tube within the first several minutes from birth. Excludes free flow oxygen only and laryngoscopy for aspiration of meconium.
  • 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. Asthma phenotypes have a number of different classifications; allergic asthma, intrinsic or nonallergic asthma, infectious asthma, and aspirin-exacerbated asthma, and environmental exposures (occupational agents, smoking, air pollution, cold dry air) (More? PMID 5439356)
  • 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.
  • Bochdalek hernia - The most common form (80-85%) of the Congenital Diaphragmatic Hernia (CDH) types occurring mainly on the postero-lateral (left) side of the respiratory diaphragm. (More? congenital diaphragmatic hernia)
  • bronchi - (Latin, bronchos = windpipe) Plural of bronchus, the two subdivisions of the trachea carrying air to the lungs. Embryologically form as an endodermal outpocket of the foregut which branch (bronchiole, subdivision of the bronchus) as they grow. Airway: trachea - bronchi - lobar bronchi - segmental bronchi - bronchioles - conducting bronchioles - terminal bronchioles - respiratory bronchioles - alveolar ducts.
  • bronchiole - A smaller branch subdivision of the respiratory tract bronchus, lack supporting cartilage skeletons and have a diameter of about 1 mm. Epithelium is initially ciliated and graduates to simple columnar epithelium and lining no longer contain mucous-producing cells.
  • bronchopulmonary dysplasia - (chronic lung disease in preterm infants) Clinical term for a heterogeneous lung disease seen in preterm (premature) infants and diagnosed within the first months of life. Condition was first described in 1967. (More? preterm birth American Lung Association)
  • canalicular stage - (fetal canalicular, canalicular phase) Term used to describe lung development, after early embryonic the second of the histological/developmental stages (pseudoglandular, fetal canalicular, terminal sac, alveolar). This stage occurs during the fetal period from week 16 to 24. During this stage there is lung bud mesenchymal angiogenesis and cellular differentiation into different stromal cell types (fibroblasts, myoblasts and chondrocytes). (embryonic stage - pseudoglandular stage - canalicular stage - saccular stage - alveolar stage)
  • carbon monoxide - (CO) A colourless and odorless gas formed mainly as a by-product of incomplete combustion of hydrocarbons and can cause cytotoxicity by tissue hypoxia. Carbon monoxide enters circulation though the respiratory system, binding to haemoglobin to form carboxy-haemoglobin (COHb), with fetal haemoglobin binding with a greater affinity.
  • CDH - Acronym for Congenital Diaphragmatic Hernia, a musculoskeletal abnormality of the respiratory diaphragm. The most common form being the Bochdalek hernia.
  • chorioamnionitis - (amnionitis, intra-amniotic infection) intrauterine bacterial infection/inflammation that can cause preterm birth and affect respiratory development directly as well as thought the underdeveloped brainstem, resulting in reduced respiratory drive.
  • chronic lung disease - (CLD) Clinical term, a neonatal chronic lung disease can be caused by prolonged mechanical ventilation (MV) and oxygen-rich gas with premature infants.
  • Clara cells - Respiratory tract epithelial cells on the luminal surface of airways. These cells have a dome shaped cytoplasmic protrusion and no cilia and their function is secretory and xenobiotic. Clara cells can act as progenitor cell in small airways replacing injured terminally differentiated epithelial cells.
  • Clara cell secretory protein - (CCSP) A protective lung protein secreted from non-ciliated bronchiolar epithelial cells in the conducting airways of mammals. The protein increases in expression level post-natally and is thought to have antioxidant, immunomodulatory, and anticarcinogenic properties.
  • connective tissue fibers - form a continuous alveolar support with axial, peripheral and septal fibers.
  • congenital diaphragmatic hernia - Abnormality due to failure of the pleuroperitoneal foramen (foramen of Bochdalek) to close (left side), allows viscera into thorax Intestine, stomach or spleen can enter the pleural cavity, compressing the lung. Rarer (Morgagni hernia) is an opening in the front of the diaphragm. (More? congenital diaphragmatic hernia | GeneReviews
  • 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).
  • corticosteroid - An endocrine steroidal hormone produced by the adrenal cortex. Clinically, corticosteroids are also used for lung maturation of the premature neonate.
  • 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)
  • diaphragm - A general term for a membranous sheet, used to describe the respiratory diaphragm. The muscular sheet separating chest from abdomen with several different embryonic origins. Regular contraction of the diaphragm is required in respiration. The diaphragm forms initially at the lower end of the pleuroperitoneal canal. (Embryonic origins: transverse septum (septum transversum) - tendon of the diaphragm, 3rd to 5th somite pairs - musculature of diaphragm, ventral pleural sac - connective tissue, mesentry of oesophagus - connective tissue around oesophasus and inferior vena cava, and pleuroperitoneal membranes - connective tissue around central tendon)
  • endoderm - (Greek, endo = inside + derma = skin) One of the initial 3 germ cell layers (ectoderm, mesoderm, endoderm) formed by the process of gastrulation. The endoderm forms the epithelial lining glands and of the respiratory tract.
  • epaxial muscle - Anatomical term describing skeletal muscles which lie dorsal (posterior) to the vertebral column developing from the somite myotome. At the ribcage level the levatores costarum muscles involved with rib elevation during respiration.
  • epiglottis - (Greek, epi = above, upon) cartilaginous part of the larynx above the glottis, which in infancy directs food into the esophagus and not the trachea . Embryologically it develops in the foregut from the hypobranchial eminence, behind the undeveloped tongue, from which it separates at about 7 weeks. Postnatal anatomical development in humans involves a maturational descent in infancy (4 and 6 months of age). Contains lymphoid tissue (larynx-associated lymphoid tissue, LALT and Bronchus-associated lymphoid tissue, BALT).
  • Extracorporeal Membrane Oxygenation - (ECMO) an invasive therapy that has been investigated and utilized in newborn infants with cardiorespiratory failure.
  • fetal breathing movements - (FBM) Occur in the third trimester preparing both the skeletomuscular and neural system, and lungs mechanically and the amount of liquid within the developing lungs.
  • fistula - An abnormal communication between 2 structures (organs, vessels, cavities) that do not normally connect, can occur between the trachea and oesophagus.
  • foregut - The first of the three part/division (foregut - midgut - hindgut) of the early forming gastrointestinal tract. The foregut runs from the buccopharyngeal membrane to the midgut and forms all the tract (esophagus and stomach) from the oral cavity to beneath the stomach. In addition, a ventral bifurcation of the foregut will also form the respiratory tract epithelium.
  • glottis - (Greek, = larynx) the boundary between pharynx to the larynx and consists of the vocal folds and their associated intervening space.
  • HIF-1 - A transcription factor that is one of the main regulators of homeostasis in human tissues exposed to hypoxia, due to inflammation and/or insufficient circulation.
  • hyaline membrane disease - (Newborn Respiratory Distress Syndrome) Abnormality due to a membrane-like substance from damaged pulmonary cells.
  • hypopharynx - connects the oropharynx to the oesophagus and the larynx, the region of pharynx below the hyoid bone.
  • laryngeal cleft - (LC, laryngeal-tracheo-oesophageal cleft) A rare foregut abnormality allowing digestive tract and the airway to communicate causing chronic cough, aspiration and respiratory distress. The downward extension of the cleft determines the classification of the abnormality.
  • laryngeal webs - (congenital laryngeal webs) Laryngeal abnormality due to embryonic (week 10) incomplete recanalization of the laryngotracheal tube. Rare abnormality occuring mainly at the level of the vocal folds (glottis).
  • laryngotracheal groove - Early embryonic foregut developmental feature, forms on the anterior (ventral) wall of the pharynx and gives rise to larynx, trachea and entire respiratory tree. In humans, this feature is the first indication of respiratory development and appears during week 4.
  • larynx - Site of the the vocal folds in the neck. Embryologically develops from the foregut with the lining derived from endoderm and the cartilage from pharyngeal arch 4 and 6. Beginning as a simple foregut groove, the laryngotracheal groove which folds to form the laryngotracheal bud, then the larynx and trachea.
  • late-gestation lung protein 1 - (LGL1) A glycoprotein secreted by fetal lung mesenchyme and fetal kidney, involved in retinoic acid stimulated branching morphogenesis.
  • lipofibroblast - (lipid interstitial cell, pulmonary lipofibroblast) Cell involved in secondary septum formation during the alveolar stage of lung development (late fetal to postnatal). Cell is recognizable by a number of characteristic lipid droplets and contains cortical contractile filaments.
  • lobar emphysema - (overinflated lung) Abnormality of an overinflated left upper lobe There is a collapsed lower lobe The left lung is herniating across the mediastinum.
  • measles - (paramyxovirus) Measles (rubeola) is mainly a respiratory viral infection, clinically different from Rubella.
  • meconium aspiration syndrome - (MAS) 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.
  • medullary respiratory centres - medulla oblongata collection of nuclei organised into ventral and dorsal respiratory groups. The ventral respiratory nuclei pre-Bötzinger complex (pBÖTC) required for respiratory rhythmogenesis.
  • mitochondria - Double membraned cell organelle located in the cytoplasm, a cell may contain 100's or more mitochondria, the number can relate to the metabolic activity of that cell. Functions in cell respiration, providing energy to the cell and also has a role in the process of apoptosis (programmed cell death).
  • newborn respiratory distress syndrome - (respiratory distress syndrome, RDS, hyaline membrane syndrome) - surfactant deficiency at birth more common in preterm birth. RDS Info
  • nitrofen - A diphenyl ether herbicide teratogen used in rodent development to generate a range of developmental abnormalities, including congenital diaphragmatic hernia.
  • oropharynx - The second portion of the pharynx (throat) connecting the nasopharynx and laryngopharynx (hypopharynx). Region between the palate and the hyoid bone, anteriorly divided from the oral cavity by the tonsillar arch.
  • parathyroid hormone-related protein - (PTHrP) A protein named for its evolutionary and structural relationship to parathyroid hormone (PTH). A protein hormone produced by many fetal tissues and with a number of different functions including a possible autocrine role in lung development.
  • parietal pleura - Serous membrane which forms the outer lining of pleural cavity. mesoderm of the thoracic cavity body wall and derived from epithelia of pericardioperitoneal canals from intra-embryonic coelom. The inner pleural layer, visceral pleura, is splanchnic mesoderm in origin.
  • Pentalogy of Cantrell - A developmental abnormality of the anterior diaphragm, diaphragmatic pericardium, abdominal wall, cardiovascular and lower sternum.
  • Persistent Pulmonary Hypertension of the Newborn - (PPHN) A serious newborn condition due to due to the failure of closure one of the prenatal circulatory shunts, the ductus arteriosus. Occurs in about 1-2 newborns per 1000 live births and results in hypoxemia.
  • pharynx - (throat) embryo uppermost end of the combined gastrointestinal and respiratory tract beginning at the buccopharyngeal membrane and forms a major arched cavity within the phrayngeal arches. Also used as a respiratory term describing the initial segment of the upper respiratory tract divided anatomically into three regions: nasopharynx, oropharynx, and laryngopharynx (hypopharynx). Anatomically extends from the base of the skull to the level of the sixth cervical vertebra.
  • pleural cavity - Anatomical body cavity in which the lungs develop and lie. Forms in the lateral plate mesoderm as part of the early single intra-embryonic coelom, the pleural cavities are initially two narrow canals.
  • 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 foramen - The developmental opening occurring in the intra-embryonic coelom before formation of the pleuroperitoneal membrane.
  • PLUNC - Acronym for Palate, LUng, Nasal epithelium Clone protein, related to the lipid transfer/lipopolysaccharide binding protein (LT/LBP) family. This protein is secreted by the airway conducting epithelia and acts as a surfactant that may interfere with biofilm formation by airway pathogens.
  • pulmonary acini (singular - acinus) region of the lung supplied with air from one of the terminal bronchioles, anatomical and functional end of the mammalian lung respiratory tree where gas exchange occurs. Starts approximately 3 to 4 generations proximal of the bronchio-alveolar duct junction and ends about 4 generations of alveolar ducts distal of the bronchioalveolar duct junction.
  • pulmonary arterial hypertension - (PAH) a progressive disease characterized by abnormalities of vascular tone and reactivity, vessel wall structure, growth, and thrombosis that in newborns, infants, and children can contribute to poor outcomes in cardiac, pulmonary, and systemic diseases.
  • respiratory - Term used in relation to breathing (in and out) or associated with the lungs. Anatomically used to describe the lungs, air pathways and associated muscles. In cell biology used in relation to mitochondrial use of oxygen to produce energy and carbon dioxide waste.
  • respiratory bronchioles - may contain alveoli and have surface surfactant-producing Respiratory bronchioles can contain alveoli and surfactant-producing cells, and give rise to between 2 to 11 alveolar ducts.
  • respiratory sinus arrhythmia - (RSA) Clinically used as an index of cardiac vagal activity, measured breath-by-breath by subtracting the minimum heart rate (HR) during expiration from the maximum HR during inspiration.
  • respiratory tree - Anatomical term to describe the components of the respiratory system (lungs) as they branch again and again ending in the functional units, the alveolar sacs (alveolus).
  • saccular stage - (terminal sac stage) process of lung epithelial cell differentiation, vascular remodeling and thinning of the mesenchyme. This process leads to enlargement of the diameter and surface area of the alveolar sacs. Distal epithelial cells form 2 populations: 1. cells flattens, thins, and spreads to form type I cells; 2. cells remain cuboidal, acquire surfactant filled lamellar bodies and differentiate into type II cells. Sacculation is a general anatomical term meaning to formed a series of sac-like expansions. (embryonic stage - pseudoglandular stage - canalicular stage - saccular stage - alveolar stage)
  • secondary septa - (secondary septa) process in the lung alveolar stage of development (postnatally) where the double capillary network in the immature gas-exchange region fuses to form a single capillary layer.
  • septum transversum - (transverse septum) A mesodermal region in the early embryo. Identified externally as the junctional site between amnion and yolk sacs, and internally (within the embryo) lying directly beneath the heart and at the foregut/midgut junction. This ventro-dorsal "plate" of mesoderm contributes several structures including: the central tendon of diaphragm and some of the liver.
  • stenosis - Term used to describe an abnormal narrowing, usually in relation to a tube for example: respiratory tract, blood vessel, gastrointestinal tract.
  • stomodeum - (stomadeum, stomatodeum) The primordial mouth region of the developing embryonic head.
  • surfactant - (surface active agent ; pulmonary surfactant) A mixture of lipids and proteins secreted by Type 2 alveolar cells between alveolar epithelium that reduces surface tension (detergent) at the air-liquid interface. The function is to prevent collapse of the lung at the end of expiration. In humans, these cells and their secretion develop towards the very end of the third trimester, just before birth. Clinical surfactants used for surfactant replacement therapy are animal-derived preparations, commonly bovine (beractant, bovactant, BLES) or less common porcine (butantan, poractant-α and surfacen) PMID30728009.
  • surfactant protein D - (SP-D) a multimeric collectin (collagen-containing C-type lectin) involved in innate immunity (anti-microbial) and expressed in pulmonary and non-pulmonary epithelia. PMID 29473039
  • surfactant replacement therapy - (surfactant therapy) A clinical birth term referring to the endotracheal instillation of a surface-active suspension for treating surfactant deficiency due to either preterm birth or pulmonary injury resulting in respiratory distress (newborn respiratory distress syndrome).
  • tachypnea - (Greek, tachypnea = rapid breathing) Clinical term describing an increased respiratory rate of greater than 60 breaths/minute in a quiet resting baby.
  • terminal sac stage - (saccular stage, terminal sac phase, immature alveoli) Term used to describe the second last histological/developmental stage (pseudoglandular stage, Fetal Canalicular, saccular stage, Alveolar) of lung development. This stage occurs from late fetal week 24 to 36. During this stage branching and growth of the terminal sacs occurs, with cellular differentiation of the type -II pneumonocytes and type - I pneumonocytes The final functional sac of the respiratory tree occurs at the next neonatal period, where gas exchange occurs between the alveolar space and the pulmonary capillaries. (embryonic stage - pseudoglandular stage - canalicular stage - saccular stage - alveolar stage)
  • trachea - (windpipe) In the embryo, a ventral out-pocket of pharynx endoderm that branches in week 4 stage 13 into the right and left bronchi within the lung buds. The endoderm has associated mesoderm that later differentiates to form most structures outside the respiratory epithelium. In the adult, the trachea forms the functional connection between the pharynx and larynx to the lungs. Adult trachea is a ciliated pseudostratified columnar epithelium supported by C-shaped rings of hyaline cartilage.
  • tracheoesophageal fistula - Abnormal connection between the trachea and oesophagus.
  • Trisomy 21 - (Down syndrome) associated with significant cardiovascular and pulmonary mortality and morbidity of neonates, infants, and children. Infant lung histology may share features of decreased lung vascular and alveolar growth. (More? Trisomy 21 | PMID 25621156)
  • vagus - (Latin, vagus = wandering) cranial nerve X (CN X) A mixed nerve that leaves the head and neck to innervate respiratory tract (larynx, lungs), gastrointestinal tract (pharynx, esophagus, stomach), cardiac (heart) and abdominal viscera. This mixed nerve has sensory, motor and autonomic functions of viscera (glands, digestion, heart rate).
  • vasculogenesis - the formation of new blood vessels from angioblasts or endothelial progenitor cells (EPCs) that migrate, differentiate, and grow into tubes in response to signals from surrounding cells. (see also angiogenesis).
  • VEGF - (vascular endothelial growth factor) a specific mitogen and survival factor required for endothelium growth and development also required in lung vasculature development and remodelling.
  • ventilatory unit - region from a respiratory bronchiole extending to the supported alveolar ducts and alveoli.
  • visceral pleura - Serous membrane which forms the inner lining of pleural cavity, both covering and attached to the lungs. Embryonically derived from the splanchnic mesoderm. The outer pleural layer, parietal pleura, is derived from mesoderm of the thoracic cavity body wall.
Other Terms Lists  
Terms Lists: ART | Birth | Bone | Cardiovascular | Cell Division | Endocrine | Gastrointestinal | Genital | Genetic | Head | Hearing | Heart | Immune | Integumentary | Neonatal | Neural | Oocyte | Palate | Placenta | Radiation | Renal | Respiratory | Spermatozoa | Statistics | Tooth | Ultrasound | Vision | Historic | Drugs | Glossary

Additional Information

Additional Information - Content shown under this heading is not part of the material covered in this class. It is provided for those students who would like to know about some concepts or current research in topics related to the current class page.
Developing Rat Lung (3D view)  
From transitional bronchiole to alveolus!

The flight starts by entering a transitional bronchiole.

Domes of Club cell are visible on the surface of the bronchiole. Turning left an alveolar duct is entered. Various alveoli and the entrance of few alveolar ducts are visible. Shortly before the end of first alveolar duct, the fight turns left again and flies down another alveolar duct. After a short distance it ends in front of an alveolus which is subdivided by a low ridge representing a still forming new alveolar septum. Rat lung at postnatal day 36.

Surface rendering of a sample scanned by SRXTM for Schittny et al. (Schittny et al. 2008) using the software Imaris 4.1 (Bitplane, Zürich, Switzerland). Because the magnification is changing during the flight a scale bar could not be easily shown. However, the entrance of the bronchiole has a diameter of ~100 µm (text from suppl. information)

Schittny JC. (2018). How high resolution 3-dimensional imaging changes our understanding of postnatal lung development. Histochem. Cell Biol. , 150, 677-691. PMID: 30390117 DOI.


Note - mouse and rat the acini and the ventilatory units are the same entity because they do not possess any respiratory bronchioles. The mouse model (C57BL/6J) completely lacks respiratory breathing movements seen in the human fetus. [16]

Respiratory Quiz


Lung Development - Respiratory Health and Disease

Nikolić MZ, Sun D & Rawlins EL. (2018). Human lung development: recent progress and new challenges. Development , 145, . PMID: 30111617 DOI.

Arigliani M, Spinelli AM, Liguoro I & Cogo P. (2018). Nutrition and Lung Growth. Nutrients , 10, . PMID: 30021997 DOI.

Finke I, de Jongste JC, Smit HA, Wijga AH, Koppelman GH, Vonk J, Brunekreef B & Gehring U. (2018). Air pollution and airway resistance at age 8 years - the PIAMA birth cohort study. Environ Health , 17, 61. PMID: 30016982 DOI.

Stocks J, Hislop A & Sonnappa S. (2013). Early lung development: lifelong effect on respiratory health and disease. Lancet Respir Med , 1, 728-42. PMID: 24429276 DOI.

Merkus PJ. (2003). Effects of childhood respiratory diseases on the anatomical and functional development of the respiratory system. Paediatr Respir Rev , 4, 28-39. PMID: 12615030


adult lungs
Grays - Respiratory Images
Respiratory Histology  

Histology will be covered in more detail in your associated practical class.

Fetal Histology

Fetal Respiratory: late canalicular | unlabeled late canalicular | Hyaline cartilage | Respiratory Histology

Adult Histology

Respiratory Histology: Bronchiole | Alveolar Duct | Alveoli | EM Alveoli septum | Alveoli Elastin | Trachea 1 | Trachea 2 | labeled lung | unlabeled lung | Respiratory Bronchiole | Lung Reticular Fibres | Nasal Inferior Concha | Nasal Respiratory Epithelium | Olfactory Region overview | Olfactory Region Epithelium | Histology Stains

References

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  2. Schittny JC. (2017). Development of the lung. Cell Tissue Res. , 367, 427-444. PMID: 28144783 DOI.
  3. Stabler CT & Morrisey EE. (2017). Developmental pathways in lung regeneration. Cell Tissue Res. , 367, 677-685. PMID: 27957616 DOI.
  4. 4.0 4.1 Gauthier TW & Brown LA. (2017). In utero alcohol effects on foetal, neonatal and childhood lung disease. Paediatr Respir Rev , 21, 34-37. PMID: 27613232 DOI.
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  6. Knudsen L & Ochs M. (2018). The micromechanics of lung alveoli: structure and function of surfactant and tissue components. Histochem. Cell Biol. , 150, 661-676. PMID: 30390118 DOI.
  7. Schittny JC. (2018). How high resolution 3-dimensional imaging changes our understanding of postnatal lung development. Histochem. Cell Biol. , 150, 677-691. PMID: 30390117 DOI.
  8. Yamamoto M, Wilting J, Abe H, Murakami G, Rodríguez-Vázquez JF & Abe SI. (2018). Development of the pulmonary pleura with special reference to the lung surface morphology: a study using human fetuses. Anat Cell Biol , 51, 150-157. PMID: 30310706 DOI.
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  15. Miller MD & Marty MA. (2010). Impact of environmental chemicals on lung development. Environ. Health Perspect. , 118, 1155-64. PMID: 20444669 DOI.
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Cite this page: Hill, M.A. (2019, November 14) Embryology SH Lecture - Respiratory System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/SH_Lecture_-_Respiratory_System_Development

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G