2017 Group Project 5 - Revision history

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2017-10-26T22:16:36Z

Protected "2017 Group Project 5" ([Edit=Allow only administrators] (indefinite) [Move=Allow only administrators] (indefinite))

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Revision as of 09:16, 27 October 2017

Z5076351: /* Lungs */

2017-10-26T05:08:43Z

Lungs

← Older revision		Revision as of 16:08, 26 October 2017
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	=Lungs=		=Lungs=

	The lungs as our breathing organs are quite unnecessary during an embryo’s intrauterine existence. However, the development of the lungs during this time is absolutely essential so that they are ready to function immediately following birth. Therefore, the lungs undergo a vast period of development from the embryonic period to the foetal period to birth and beyond. Despite this, the lungs are still a vital source of amniotic fluid during a foetus’ intrauterine life.		The lungs are our breathing organs and are quite unnecessary during an embryo’s intrauterine existence. However, the development of the lungs during this time is absolutely essential so that they are ready to function immediately following birth. Therefore, the lungs undergo a vast period of development from the embryonic period to the foetal period to birth and beyond. Despite this, the lungs are still a vital source of amniotic fluid during a foetus’ intrauterine life.

	On this page, we explore in detail the stages of embryonic development of the lungs with a deeper insight into the two main physiological aspects of the lungs: the conducting system and the alveoli. This page will also outline the relevant signalling processes involved, animal models that represent research in this area and the abnormalities that may arise from issues in the developmental process.		On this page, we explore in detail the stages of embryonic development of the lungs with a deeper insight into the two main physiological aspects of the lungs: the conducting system and the alveoli. This page will also outline the relevant signalling processes involved, animal models that represent research in this area and the abnormalities that may arise from issues in the developmental process.

Z5076351: /* Bronchopulmonary dysplasia */

2017-10-26T05:03:01Z

Bronchopulmonary dysplasia

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	===Bronchopulmonary dysplasia===		===Bronchopulmonary dysplasia===

	Bronchopulmoary dysplasia (BPD) is described as a chronic lung condition derived from the disruption of normal pulmonary vascular and alveolar growth in infants born less than 28 weeks' gestation.<ref name="PMID24666156"><pubmed>24666156</pubmed></ref> Initially, BPD was said to be caused by treatment of NDRS by using mechanical ventilation. This ventilation was used to provide oxygen to infants who could not breathe on their own. However, a variety of factors from ventilation, such as infection, inflammation and oxygen toxicity, could stunt the postnatal maturation of the lungs, resulting in blunted alveolarization and dysmorphic pulmonary vasculature.<ref name="PMID26361876"><pubmed>26361876</pubmed></ref> In recent times, antenatal and perinatal factors ~~that might~~ disrupt lung development in extremely premature infants are also said to be the cause of BPD.<ref name="PMID4469359"><pubmed>4469359</pubmed></ref>		Bronchopulmoary dysplasia (BPD) is described as a chronic lung condition derived from the disruption of normal pulmonary vascular and alveolar growth in infants born less than 28 weeks' gestation.<ref name="PMID24666156"><pubmed>24666156</pubmed></ref> Initially, BPD was said to be caused by treatment of NDRS by using mechanical ventilation. This ventilation was used to provide oxygen to infants who could not breathe on their own. However, a variety of factors from ventilation, such as infection, inflammation and oxygen toxicity, could stunt the postnatal maturation of the lungs, resulting in blunted alveolarization and dysmorphic pulmonary vasculature.<ref name="PMID26361876"><pubmed>26361876</pubmed></ref> In recent times, antenatal and perinatal factors found to disrupt lung development in extremely premature infants are also said to be the cause of BPD.<ref name="PMID4469359"><pubmed>4469359</pubmed></ref>

	===Meconium Aspiration Syndrome===		===Meconium Aspiration Syndrome===

Z5062492: /* Lung Cardiovasculature */

2017-10-26T04:55:44Z

Lung Cardiovasculature

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	==Lung Cardiovasculature==		==Lung Cardiovasculature==

	[[File:lungvasc.png\|thumb\|Figure 3]]		[[File:lungvasc.png\|thumb\|'''Figure 3.''' The cardiovasculature of the adult lungs.]]

	Figure 3 shows the connection between the heart and the lungs, showing the pulmonary arteries and veins in the lungs. The heart and lungs are interdependent in embryonic development. Since vascular development exists prior to respiratory development, the way cardiovasculature interacts with lung anatomy and functioning is extremely significant. <ref name="PMCID3641728"><pubmed>PMC3641728</pubmed></ref>		Figure 3 shows the connection between the heart and the lungs, showing the pulmonary arteries and veins in the lungs. The heart and lungs are interdependent in embryonic development. Since vascular development exists prior to respiratory development, the way cardiovasculature interacts with lung anatomy and functioning is extremely significant. <ref name="PMCID3641728"><pubmed>PMC3641728</pubmed></ref>

Z5059373: /* Developmental timeline */

2017-10-26T04:52:38Z

Developmental timeline

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	\|-bgcolor="F5FAFF"		\|-bgcolor="F5FAFF"
	\| width="40" \|<center>'''Saccular (weeks 24-40)'''</center>		\| width="40" \|<center>'''Saccular (weeks 24-40)'''</center>
	\| width="65" \|The Saccular stage shows a marked decrease in the interstitium, making way for growing peripheral airways or saccules. The widening of these saccules marks the regions of future gas exchange in the lung. Capilliaries surround these saccules to form a capillary bilayer in the intersaccular primary septa <ref name="PMID6370120"><pubmed>6370120</pubmed></ref>. Throughout this stage, Type I and Type II pneumocytes can be identified. Type II pneumocytes have lamellar bodies that contain surfactant; a phospholipoprotein which is essential for the inflation of the lungs and to prevent their collapse. It is important for the first breath of a newborn; the higher the number of lamellar bodies corresponds to increased stability in lung functioning at birth. Babies born prematurely that have reached this stage of lung development have a chance of surviving, directly relating to the number of lamellar bodies present.<ref> Rothstein, P. 2017. Lung Development. Columbia University. Retrieved from :http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf </ref>		\| width="65" \|The Saccular stage shows a marked decrease in the interstitium, making way for growing peripheral airways or saccules. The widening of these saccules marks the regions of future gas exchange in the lung. Capilliaries surround these saccules to form a capillary bilayer in the intersaccular primary septa <ref name="PMID6370120"><pubmed>6370120</pubmed></ref>. Throughout this stage, Type I and Type II pneumocytes can be identified; their structure is shown in Figure 7. Type II pneumocytes have lamellar bodies that contain surfactant; a phospholipoprotein which is essential for the inflation of the lungs and to prevent their collapse. It is important for the first breath of a newborn; the higher the number of lamellar bodies corresponds to increased stability in lung functioning at birth. Babies born prematurely that have reached this stage of lung development have a chance of surviving, directly relating to the number of lamellar bodies present.<ref> Rothstein, P. 2017. Lung Development. Columbia University. Retrieved from :http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf </ref>
	\| width="65" \| In 1921, Von Neergaard discovered the function of pulmonary surfactant in newborns but the importance of his work was not recognised until the 1950s when it was rediscovered. <ref name="PMID9813256"><pubmed>9813256</pubmed></ref>The rediscovery was significant for the further understanding of Respiratory Distress Syndrome (RDS); in 1959, Avery and Mead discovered that premature infants suffering from RDS were more often surfactant deficient than not.<ref name="PMID13649082"><pubmed>13649082</pubmed></ref> This boosted research in the area of surfactant.		\| width="65" \| In 1921, Von Neergaard discovered the function of pulmonary surfactant in newborns but the importance of his work was not recognised until the 1950s when it was rediscovered. <ref name="PMID9813256"><pubmed>9813256</pubmed></ref>The rediscovery was significant for the further understanding of Respiratory Distress Syndrome (RDS); in 1959, Avery and Mead discovered that premature infants suffering from RDS were more often surfactant deficient than not.<ref name="PMID13649082"><pubmed>13649082</pubmed></ref> This boosted research in the area of surfactant.
	\| width="65" \| [[File:Alveolus.png\|thumb\| Figure 7. Structure of an alveolus including the structures of both Pneumocyte I and II, surfactant and lamellar body <ref name="PMID2195058"><pubmed>2195058</pubmed></ref>]]		\| width="65" \| [[File:Alveolus.png\|thumb\| Figure 7. Structure of an alveolus including the structures of both Pneumocyte I and II, surfactant and lamellar body <ref name="PMID2195058"><pubmed>2195058</pubmed></ref>]]
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	\| width="40" \|<center>'''Alveolar (week 36-8 years)'''</center>		\| width="40" \|<center>'''Alveolar (week 36-8 years)'''</center>
	\| width="65" \| This is the final stage of lung development that stretches from late fetal to early childhood. This stage involves the formation of a secondary septa and its fusing with the primary septa to produce a more effective single-layered capillary network. This is part of a process called microvascular maturation. <ref name="PMID28144783"/> In the classical mode of alveolarization, it was believed that after the formation of the new septa that alveolarizatoin ceased. However, more recent evidence has proved otherwise and shown alveolarization occurs from this stage and continues post-natally, this was termed "Continued alveolarization". ~~The differences in~~ these are shown in ~~the accompanying figure~~. Once a child is born, massive changes occur in lung development. The alveoli formed prenatally, sometimes referred to as "primitive saccules", continue to mature and fully form up until a child is 8-10 years old. At birth, these primitive saccules number approximately 20 million and continue to develop to reach numbers of 300 million alveoli by childhood.<ref name="PMID7850362"/>		\| width="65" \| This is the final stage of lung development that stretches from late fetal to early childhood. This stage involves the formation of a secondary septa and its fusing with the primary septa to produce a more effective single-layered capillary network. This is part of a process called microvascular maturation. <ref name="PMID28144783"/> In the classical mode of alveolarization, it was believed that after the formation of the new septa that alveolarizatoin ceased. However, more recent evidence has proved otherwise and shown alveolarization occurs from this stage and continues post-natally, this was termed "Continued alveolarization". Both these models are shown in Figure 8. Once a child is born, massive changes occur in lung development. The alveoli formed prenatally, sometimes referred to as "primitive saccules", continue to mature and fully form up until a child is 8-10 years old. At birth, these primitive saccules number approximately 20 million and continue to develop to reach numbers of 300 million alveoli by childhood.<ref name="PMID7850362"/>
	\| width="65" \| The Alveolarization stage of lung development has been increasingly well documented in the recent years corresponding to increasing technological advances. Traditionally, the counting of alveoli was done by assuming the structure of the alveolus and using a general equation to calculate total alveoli volume. This approach by Weibel and Gomez in 1962 set the stage for the first method of counting alveoli. <ref name="PMID14005589"><pubmed>14005589</pubmed></ref>. In 2004, Hyde et al. used a method of unbiased disector princple to estimate the Euler characteristic (a polyhedron formula) which gives an estimate of alveolar volume in the lung or in a certain section of it. An important improvement here is the implementation of an unbiased principle for the estimates made. <ref name="PMID14983516"><pubmed>14983516</pubmed></ref>		\| width="65" \| The Alveolarization stage of lung development has been increasingly well documented in the recent years corresponding to increasing technological advances. Traditionally, the counting of alveoli was done by assuming the structure of the alveolus and using a general equation to calculate total alveoli volume. This approach by Weibel and Gomez in 1962 set the stage for the first method of counting alveoli. <ref name="PMID14005589"><pubmed>14005589</pubmed></ref>. In 2004, Hyde et al. used a method of unbiased disector princple to estimate the Euler characteristic (a polyhedron formula) which gives an estimate of alveolar volume in the lung or in a certain section of it. An important improvement here is the implementation of an unbiased principle for the estimates made. <ref name="PMID14983516"><pubmed>14983516</pubmed></ref>
	\| width="65" \| [[File:Alveolarization.gif\|thumb\| Figure 8. Classic and continued alveolarization in the final stage of lung development<ref name="PMID28144783"/>]]		\| width="65" \| [[File:Alveolarization.gif\|thumb\| Figure 8. Classic and continued alveolarization in the final stage of lung development<ref name="PMID28144783"/>]]

Z5062492: /* Lung Histology */

2017-10-26T04:51:16Z

Lung Histology

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	===Lung Histology===		===Lung Histology===
	[[File:Respiratory histology 08.jpg\|thumb\|Figure 2]]		[[File:Respiratory histology 08.jpg\|thumb\|'''Figure 2.''' The histology of the adult lungs.]]
	Figure 2 <ref>Hill, M.A. 2017 Embryology Respiratory histology 08.jpg. Retrieved October 25, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/File:Respiratory_histology_08.jpg</ref> shows the histology of the lung.		Figure 2 <ref>Hill, M.A. 2017 Embryology Respiratory histology 08.jpg. Retrieved October 25, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/File:Respiratory_histology_08.jpg</ref> shows the histology of the lung.

Z5062492: /* Lung Anatomy */

2017-10-26T04:49:10Z

Lung Anatomy

← Older revision		Revision as of 15:49, 26 October 2017
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	===Lung Anatomy===		===Lung Anatomy===

	[[File:lunganat1.png\|thumb\|Figure 1]]		[[File:lunganat1.png\|thumb\|'''Figure 1.''' The anatomy of the adult lung.]]
	To understand lung embryology, we must first understand what a fully grown adult lung looks and functions like, anatomically and histologically.		To understand lung embryology, we must first understand what a fully grown adult lung looks and functions like, anatomically and histologically.

	~~Figure 1 shows the anatomy of the adult lung.~~ The larger right lung consists of 3 lobes (superior, middle & inferior) whereas the smaller left lung has 2 lobes (superior & inferior). The trachea splits into the left and right bronchi in the lungs. The bronchi are hollow tubes composed for hyaline cartilage and are lined with respiratory epithelium which is '''ciliated pseudostratified epithelium'''. <ref>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.</ref>		The larger right lung consists of 3 lobes (superior, middle & inferior) whereas the smaller left lung has 2 lobes (superior & inferior). The trachea splits into the left and right bronchi in the lungs. The bronchi are hollow tubes composed for hyaline cartilage and are lined with respiratory epithelium which is '''ciliated pseudostratified epithelium'''. <ref>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.</ref>

	Each lung receives air through these '''primary bronchi'''. As these primary bronchi enter the lungs, they branch into smaller '''secondary bronchi''' which carry air to each lobe of the lungs.		Each lung receives air through these '''primary bronchi'''. As these primary bronchi enter the lungs, they branch into smaller '''secondary bronchi''' which carry air to each lobe of the lungs.

Z5076351: /* Animal models */

2017-10-26T04:36:53Z

Animal models

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	'''~~Mouse~~ models'''		'''Mice models'''

	~~Mouse~~ models have been widely used in the genetic field of research as it shares many common features with the human genome. By manipulating the gene pool, we are able to examine the physiology and anatomy of mice offsprings with selected gene characteristics. <ref name="PMID25636466 "><pubmed>25636466 </pubmed></ref>		Mice models have been widely used in the genetic field of research as it shares many common features with the human genome. By manipulating the gene pool, we are able to examine the physiology and anatomy of mice offsprings with selected gene characteristics. <ref name="PMID25636466 "><pubmed>25636466 </pubmed></ref>
	The low costs of mice, short reproductive cycle and lifespan make mice a perfect animal model to observe lung embryology. Some disadvantages that come with mice models are that they are significantly smaller than humans and have immunological differences, such as a lack of IL-8. <ref name="PMID25636466 "><pubmed>25636466 </pubmed></ref>		The low costs of mice, short reproductive cycle and lifespan make mice a perfect animal model to observe lung embryology. Some disadvantages that come with mice models are that they are significantly smaller than humans and have immunological differences, such as a lack of IL-8. <ref name="PMID25636466 "><pubmed>25636466 </pubmed></ref>

Z5059373: /* Developmental timeline */

2017-10-26T04:33:37Z

Developmental timeline

Z5114217: /* Alveolus: the functional unit */

2017-10-26T04:28:25Z

Alveolus: the functional unit

← Older revision		Revision as of 15:28, 26 October 2017
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	===Alveolus: the functional unit===		===Alveolus: the functional unit===

	The alveolus are small "sac-like structures" in which gas exchange occurs across. Within the alveolus there are two types of cells that line the sacs. These are type I and type II alveolar cells, these cells must differentiate in a process known as alveolar differentiation and are both crucial for gas exchange ~~<ref><pubmed>24004663</pubmed></ref>~~.		The alveolus are small "sac-like structures" in which gas exchange occurs across. Within the alveolus there are two types of cells that line the sacs. These are type I and type II alveolar cells, these cells must differentiate in a process known as alveolar differentiation and are both crucial for gas exchange.

	'''Type I:''' Type I cells are flat and cover more than 90% of the alveolar surface in which gases diffuse across.		'''Type I:''' Type I cells are flat and cover more than 90% of the alveolar surface in which gases diffuse across.

← Older revision		Revision as of 15:52, 26 October 2017
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	\| width="40" \|<center>'''Saccular (weeks 24-40)'''</center>		\| width="40" \|<center>'''Saccular (weeks 24-40)'''</center>
	\| width="65" \|The Saccular stage shows a marked decrease in the interstitium, making way for growing peripheral airways or saccules. The widening of these saccules marks the regions of future gas exchange in the lung. Capilliaries surround these saccules to form a capillary bilayer in the intersaccular primary septa <ref name="PMID6370120"><pubmed>6370120</pubmed></ref>. Throughout this stage, Type I and Type II pneumocytes can be identified. Type II pneumocytes have lamellar bodies that contain surfactant; a phospholipoprotein which is essential for the inflation of the lungs and to prevent their collapse. It is important for the first breath of a newborn; the higher the number of lamellar bodies corresponds to increased stability in lung functioning at birth. Babies born prematurely that have reached this stage of lung development have a chance of surviving, directly relating to the number of lamellar bodies present.<ref> Rothstein, P. 2017. Lung Development. Columbia University. Retrieved from :http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf </ref>		\| width="65" \|The Saccular stage shows a marked decrease in the interstitium, making way for growing peripheral airways or saccules. The widening of these saccules marks the regions of future gas exchange in the lung. Capilliaries surround these saccules to form a capillary bilayer in the intersaccular primary septa <ref name="PMID6370120"><pubmed>6370120</pubmed></ref>. Throughout this stage, Type I and Type II pneumocytes can be identified; their structure is shown in Figure 7. Type II pneumocytes have lamellar bodies that contain surfactant; a phospholipoprotein which is essential for the inflation of the lungs and to prevent their collapse. It is important for the first breath of a newborn; the higher the number of lamellar bodies corresponds to increased stability in lung functioning at birth. Babies born prematurely that have reached this stage of lung development have a chance of surviving, directly relating to the number of lamellar bodies present.<ref> Rothstein, P. 2017. Lung Development. Columbia University. Retrieved from :http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf </ref>
	\| width="65" \| In 1921, Von Neergaard discovered the function of pulmonary surfactant in newborns but the importance of his work was not recognised until the 1950s when it was rediscovered. <ref name="PMID9813256"><pubmed>9813256</pubmed></ref>The rediscovery was significant for the further understanding of Respiratory Distress Syndrome (RDS); in 1959, Avery and Mead discovered that premature infants suffering from RDS were more often surfactant deficient than not.<ref name="PMID13649082"><pubmed>13649082</pubmed></ref> This boosted research in the area of surfactant.		\| width="65" \| In 1921, Von Neergaard discovered the function of pulmonary surfactant in newborns but the importance of his work was not recognised until the 1950s when it was rediscovered. <ref name="PMID9813256"><pubmed>9813256</pubmed></ref>The rediscovery was significant for the further understanding of Respiratory Distress Syndrome (RDS); in 1959, Avery and Mead discovered that premature infants suffering from RDS were more often surfactant deficient than not.<ref name="PMID13649082"><pubmed>13649082</pubmed></ref> This boosted research in the area of surfactant.
	\| width="65" \| [[File:Alveolus.png\|thumb\| Figure 7. Structure of an alveolus including the structures of both Pneumocyte I and II, surfactant and lamellar body <ref name="PMID2195058"><pubmed>2195058</pubmed></ref>]]		\| width="65" \| [[File:Alveolus.png\|thumb\| Figure 7. Structure of an alveolus including the structures of both Pneumocyte I and II, surfactant and lamellar body <ref name="PMID2195058"><pubmed>2195058</pubmed></ref>]]
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	\| width="40" \|<center>'''Alveolar (week 36-8 years)'''</center>		\| width="40" \|<center>'''Alveolar (week 36-8 years)'''</center>
	\| width="65" \| This is the final stage of lung development that stretches from late fetal to early childhood. This stage involves the formation of a secondary septa and its fusing with the primary septa to produce a more effective single-layered capillary network. This is part of a process called microvascular maturation. <ref name="PMID28144783"/> In the classical mode of alveolarization, it was believed that after the formation of the new septa that alveolarizatoin ceased. However, more recent evidence has proved otherwise and shown alveolarization occurs from this stage and continues post-natally, this was termed "Continued alveolarization". ~~The differences in~~ these are shown in ~~the accompanying figure~~. Once a child is born, massive changes occur in lung development. The alveoli formed prenatally, sometimes referred to as "primitive saccules", continue to mature and fully form up until a child is 8-10 years old. At birth, these primitive saccules number approximately 20 million and continue to develop to reach numbers of 300 million alveoli by childhood.<ref name="PMID7850362"/>		\| width="65" \| This is the final stage of lung development that stretches from late fetal to early childhood. This stage involves the formation of a secondary septa and its fusing with the primary septa to produce a more effective single-layered capillary network. This is part of a process called microvascular maturation. <ref name="PMID28144783"/> In the classical mode of alveolarization, it was believed that after the formation of the new septa that alveolarizatoin ceased. However, more recent evidence has proved otherwise and shown alveolarization occurs from this stage and continues post-natally, this was termed "Continued alveolarization". Both these models are shown in Figure 8. Once a child is born, massive changes occur in lung development. The alveoli formed prenatally, sometimes referred to as "primitive saccules", continue to mature and fully form up until a child is 8-10 years old. At birth, these primitive saccules number approximately 20 million and continue to develop to reach numbers of 300 million alveoli by childhood.<ref name="PMID7850362"/>
	\| width="65" \| The Alveolarization stage of lung development has been increasingly well documented in the recent years corresponding to increasing technological advances. Traditionally, the counting of alveoli was done by assuming the structure of the alveolus and using a general equation to calculate total alveoli volume. This approach by Weibel and Gomez in 1962 set the stage for the first method of counting alveoli. <ref name="PMID14005589"><pubmed>14005589</pubmed></ref>. In 2004, Hyde et al. used a method of unbiased disector princple to estimate the Euler characteristic (a polyhedron formula) which gives an estimate of alveolar volume in the lung or in a certain section of it. An important improvement here is the implementation of an unbiased principle for the estimates made. <ref name="PMID14983516"><pubmed>14983516</pubmed></ref>		\| width="65" \| The Alveolarization stage of lung development has been increasingly well documented in the recent years corresponding to increasing technological advances. Traditionally, the counting of alveoli was done by assuming the structure of the alveolus and using a general equation to calculate total alveoli volume. This approach by Weibel and Gomez in 1962 set the stage for the first method of counting alveoli. <ref name="PMID14005589"><pubmed>14005589</pubmed></ref>. In 2004, Hyde et al. used a method of unbiased disector princple to estimate the Euler characteristic (a polyhedron formula) which gives an estimate of alveolar volume in the lung or in a certain section of it. An important improvement here is the implementation of an unbiased principle for the estimates made. <ref name="PMID14983516"><pubmed>14983516</pubmed></ref>
	\| width="65" \| [[File:Alveolarization.gif\|thumb\| Figure 8. Classic and continued alveolarization in the final stage of lung development<ref name="PMID28144783"/>]]		\| width="65" \| [[File:Alveolarization.gif\|thumb\| Figure 8. Classic and continued alveolarization in the final stage of lung development<ref name="PMID28144783"/>]]

← Older revision		Revision as of 15:33, 26 October 2017
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	\| width="40" \|<center>'''Embryonic (weeks 4-5)'''</center>		\| width="40" \|<center>'''Embryonic (weeks 4-5)'''</center>
	\| width="45" \| The first stage of fetal lung development is the embryonic stage where the first structural features of the lung can be seen. It is identified by the emergence of lung buds in the ventral wall of the foregut; these lung buds will later divide to form lobar divisions.The endoderm is responsible for the epithelium of the lung buds which will later differentiate into specialised respiratory epithelium. The mesoderm is responsible for the mesenchyme surrounding the lung buds.		\| width="45" \| The first stage of fetal lung development is the embryonic stage where the first structural features of the lung can be seen. It is identified by the emergence of lung buds in the ventral wall of the foregut as seen in Figure 4; these lung buds will later divide to form lobar divisions.The endoderm is responsible for the epithelium of the lung buds which will later differentiate into specialised respiratory epithelium. The mesoderm is responsible for the mesenchyme surrounding the lung buds.
	\| width="65" \| Christian Pander, Karl Ernst von Baer, and Heinrich Rathke were among the first to use a new wave of technology in embryology; involving the use of new staining techniques and improved microscopy. Their findings together identified the presence of primary germ layers (ectoderm, endoderm and mesoderm) and the development of early organs. <ref>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Comparative Embryology. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9974/</ref>		\| width="65" \| Christian Pander, Karl Ernst von Baer, and Heinrich Rathke were among the first to use a new wave of technology in embryology; involving the use of new staining techniques and improved microscopy. Their findings together identified the presence of primary germ layers (ectoderm, endoderm and mesoderm) and the development of early organs. <ref>Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Comparative Embryology. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9974/</ref>
	\| width="65" \|[[File:Early lung develop.jpg\|thumb\| Early lung development demonstrating lung buds and their growth into left and right lungs <ref name="PMID28144783 "><pubmed>28144783 </pubmed></ref>]]		\| width="65" \|[[File:Early lung develop.jpg\|thumb\| Figure 4. Early lung development demonstrating lung buds and their growth into left and right lungs <ref name="PMID28144783 "><pubmed>28144783 </pubmed></ref>]]

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	\| width="65" \| In 1970, an experiment by Spooner and Wessells demonstrated the need for the presence of surrounding bronchial mesoderm for adequate bronchial branching. <ref name="PMID5501462"><pubmed>5501462</pubmed></ref>. This was done through in vitro experiments with mice.		\| width="65" \| In 1970, an experiment by Spooner and Wessells demonstrated the need for the presence of surrounding bronchial mesoderm for adequate bronchial branching. <ref name="PMID5501462"><pubmed>5501462</pubmed></ref>. This was done through in vitro experiments with mice.
	Additionally, In 1976 Masters published his work on the importance of epithelial-mesenchymal interactions during lung development. <ref name="PMID950075"><pubmed>950075</pubmed></ref> This significance of this work is the discovery that the bronchial epithelium lining the primitive airways interacts with the mesenchyme, to then differentiate into specialised alveolar epithelium.		Additionally, In 1976 Masters published his work on the importance of epithelial-mesenchymal interactions during lung development. <ref name="PMID950075"><pubmed>950075</pubmed></ref> This significance of this work is the discovery that the bronchial epithelium lining the primitive airways interacts with the mesenchyme, to then differentiate into specialised alveolar epithelium.
	\| width="65" \| [[File:Pseudoglandular epithelium.gif\|thumb\| Epithelial structures in Pseudoglandular, Canalicular and Saccular stages of lung development <ref name="PMID28144783"/>]]		\| width="65" \| [[File:Pseudoglandular epithelium.gif\|thumb\| Figure 5. Epithelial structures in Pseudoglandular, Canalicular and Saccular stages of lung development <ref name="PMID28144783"/>]]

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	\| width="65" \|The canalicular stage is an important step in the development of the lung parenchymal cells. The formation of these cells as well as the vascularization and angiogenesis of surrounding structures is prominent in this stage. The beginning of the process producing surfactant in the lungs starts here but is more evidently seen in the Saccular stage. Additionally, there is differentiation of the specialised pulmonary epithelium into peripheral squamous cells and proximal cuboidal cells which preceeds the formation of the air-blood tissue barrier. <ref name="PMID20691848"><pubmed>20691848</pubmed></ref> At the end of this stage it is possible to distinguish between conducting and respiratory airways.		\| width="65" \|The canalicular stage is an important step in the development of the lung parenchymal cells. The formation of these cells as well as the vascularization and angiogenesis of surrounding structures is prominent in this stage. The beginning of the process producing surfactant in the lungs starts here but is more evidently seen in the Saccular stage. Additionally, there is differentiation of the specialised pulmonary epithelium into peripheral squamous cells and proximal cuboidal cells which preceeds the formation of the air-blood tissue barrier. <ref name="PMID20691848"><pubmed>20691848</pubmed></ref> At the end of this stage it is possible to distinguish between conducting and respiratory airways.
	\| width="65" \| In 1971, Edward A. Boyden published an article detailing for the first time the detailed structure of a pulmonary acinus. The presence of these acini are important for the distinction between conducting and respiratory airways in the Canalicular stage.		\| width="65" \| In 1971, Edward A. Boyden published an article detailing for the first time the detailed structure of a pulmonary acinus. The presence of these acini are important for the distinction between conducting and respiratory airways in the Canalicular stage.
	\| width="65" \| [[File:Air blood barrier.gif\|thumb\| Change in pulmonary epithelium consequently leading to formation of the air-blood barrier in the developing lung <ref name="PMID28144783"/>]]		\| width="65" \| [[File:Air blood barrier.gif\|thumb\| Figure 6. Change in pulmonary epithelium consequently leading to formation of the air-blood barrier in the developing lung <ref name="PMID28144783"/>]]


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	\| width="65" \|The Saccular stage shows a marked decrease in the interstitium, making way for growing peripheral airways or saccules. The widening of these saccules marks the regions of future gas exchange in the lung. Capilliaries surround these saccules to form a capillary bilayer in the intersaccular primary septa <ref name="PMID6370120"><pubmed>6370120</pubmed></ref>. Throughout this stage, Type I and Type II pneumocytes can be identified. Type II pneumocytes have lamellar bodies that contain surfactant; a phospholipoprotein which is essential for the inflation of the lungs and to prevent their collapse. It is important for the first breath of a newborn; the higher the number of lamellar bodies corresponds to increased stability in lung functioning at birth. Babies born prematurely that have reached this stage of lung development have a chance of surviving, directly relating to the number of lamellar bodies present.<ref> Rothstein, P. 2017. Lung Development. Columbia University. Retrieved from :http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf </ref>		\| width="65" \|The Saccular stage shows a marked decrease in the interstitium, making way for growing peripheral airways or saccules. The widening of these saccules marks the regions of future gas exchange in the lung. Capilliaries surround these saccules to form a capillary bilayer in the intersaccular primary septa <ref name="PMID6370120"><pubmed>6370120</pubmed></ref>. Throughout this stage, Type I and Type II pneumocytes can be identified. Type II pneumocytes have lamellar bodies that contain surfactant; a phospholipoprotein which is essential for the inflation of the lungs and to prevent their collapse. It is important for the first breath of a newborn; the higher the number of lamellar bodies corresponds to increased stability in lung functioning at birth. Babies born prematurely that have reached this stage of lung development have a chance of surviving, directly relating to the number of lamellar bodies present.<ref> Rothstein, P. 2017. Lung Development. Columbia University. Retrieved from :http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt12-LungDev.pdf </ref>
	\| width="65" \| In 1921, Von Neergaard discovered the function of pulmonary surfactant in newborns but the importance of his work was not recognised until the 1950s when it was rediscovered. <ref name="PMID9813256"><pubmed>9813256</pubmed></ref>The rediscovery was significant for the further understanding of Respiratory Distress Syndrome (RDS); in 1959, Avery and Mead discovered that premature infants suffering from RDS were more often surfactant deficient than not.<ref name="PMID13649082"><pubmed>13649082</pubmed></ref> This boosted research in the area of surfactant.		\| width="65" \| In 1921, Von Neergaard discovered the function of pulmonary surfactant in newborns but the importance of his work was not recognised until the 1950s when it was rediscovered. <ref name="PMID9813256"><pubmed>9813256</pubmed></ref>The rediscovery was significant for the further understanding of Respiratory Distress Syndrome (RDS); in 1959, Avery and Mead discovered that premature infants suffering from RDS were more often surfactant deficient than not.<ref name="PMID13649082"><pubmed>13649082</pubmed></ref> This boosted research in the area of surfactant.
	\| width="65" \| [[File:Alveolus.png\|thumb\|Structure of an alveolus including the structures of both Pneumocyte I and II, surfactant and lamellar body <ref name="PMID2195058"><pubmed>2195058</pubmed></ref>]]		\| width="65" \| [[File:Alveolus.png\|thumb\| Figure 7. Structure of an alveolus including the structures of both Pneumocyte I and II, surfactant and lamellar body <ref name="PMID2195058"><pubmed>2195058</pubmed></ref>]]

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	\| width="65" \| This is the final stage of lung development that stretches from late fetal to early childhood. This stage involves the formation of a secondary septa and its fusing with the primary septa to produce a more effective single-layered capillary network. This is part of a process called microvascular maturation. <ref name="PMID28144783"/> In the classical mode of alveolarization, it was believed that after the formation of the new septa that alveolarizatoin ceased. However, more recent evidence has proved otherwise and shown alveolarization occurs from this stage and continues post-natally, this was termed "Continued alveolarization". The differences in these are shown in the accompanying figure. Once a child is born, massive changes occur in lung development. The alveoli formed prenatally, sometimes referred to as "primitive saccules", continue to mature and fully form up until a child is 8-10 years old. At birth, these primitive saccules number approximately 20 million and continue to develop to reach numbers of 300 million alveoli by childhood.<ref name="PMID7850362"/>		\| width="65" \| This is the final stage of lung development that stretches from late fetal to early childhood. This stage involves the formation of a secondary septa and its fusing with the primary septa to produce a more effective single-layered capillary network. This is part of a process called microvascular maturation. <ref name="PMID28144783"/> In the classical mode of alveolarization, it was believed that after the formation of the new septa that alveolarizatoin ceased. However, more recent evidence has proved otherwise and shown alveolarization occurs from this stage and continues post-natally, this was termed "Continued alveolarization". The differences in these are shown in the accompanying figure. Once a child is born, massive changes occur in lung development. The alveoli formed prenatally, sometimes referred to as "primitive saccules", continue to mature and fully form up until a child is 8-10 years old. At birth, these primitive saccules number approximately 20 million and continue to develop to reach numbers of 300 million alveoli by childhood.<ref name="PMID7850362"/>
	\| width="65" \| The Alveolarization stage of lung development has been increasingly well documented in the recent years corresponding to increasing technological advances. Traditionally, the counting of alveoli was done by assuming the structure of the alveolus and using a general equation to calculate total alveoli volume. This approach by Weibel and Gomez in 1962 set the stage for the first method of counting alveoli. <ref name="PMID14005589"><pubmed>14005589</pubmed></ref>. In 2004, Hyde et al. used a method of unbiased disector princple to estimate the Euler characteristic (a polyhedron formula) which gives an estimate of alveolar volume in the lung or in a certain section of it. An important improvement here is the implementation of an unbiased principle for the estimates made. <ref name="PMID14983516"><pubmed>14983516</pubmed></ref>		\| width="65" \| The Alveolarization stage of lung development has been increasingly well documented in the recent years corresponding to increasing technological advances. Traditionally, the counting of alveoli was done by assuming the structure of the alveolus and using a general equation to calculate total alveoli volume. This approach by Weibel and Gomez in 1962 set the stage for the first method of counting alveoli. <ref name="PMID14005589"><pubmed>14005589</pubmed></ref>. In 2004, Hyde et al. used a method of unbiased disector princple to estimate the Euler characteristic (a polyhedron formula) which gives an estimate of alveolar volume in the lung or in a certain section of it. An important improvement here is the implementation of an unbiased principle for the estimates made. <ref name="PMID14983516"><pubmed>14983516</pubmed></ref>
	\| width="65" \| [[File:Alveolarization.gif\|thumb\| Classic and continued alveolarization in the final stage of lung development<ref name="PMID28144783"/>]]		\| width="65" \| [[File:Alveolarization.gif\|thumb\| Figure 8. Classic and continued alveolarization in the final stage of lung development<ref name="PMID28144783"/>]]
	\|}		\|}