Respiratory System - Postnatal

From Embryology

Introduction

Lung structure

This site mainly focuses on prenatal development, but the respiratory system is one of those that continues to grow and change postnatally. This page includes some topics related to this postnatal development.

Abnormalities like asthma and cystic fibrosis should also be considered with postnatal growth.


Respiratory Links: respiratory | Science Lecture | Lecture Movie | Med Lecture | Stage 13 | Stage 22 | upper respiratory tract | diaphragm | Histology | Postnatal | respiratory abnormalities | Respiratory Quiz | Respiratory terms | Category:Respiratory
Historic Embryology - Respiratory 
1902 The Nasal Cavities and Olfactory Structures | 1906 Lung | 1912 Upper Respiratory Tract | 1912 Respiratory | 1913 Prenatal and Neonatal Lung | 1914 Phrenic Nerve | 1918 Respiratory images | 1921 Respiratory | 1922 Chick Pulmonary Vessels | 1934 Right Fetal Lung | 1936 Early Human Lung | 1937 Terminal Air Passages | 1938 Human Histology

Some Recent Findings

  • How high resolution 3-dimensional imaging changes our understanding of postnatal lung development[1] "During the last 10 + years biologically and clinically significant questions about postnatal lung development could be answered due to the application of modern cutting-edge microscopic and quantitative histological techniques. These are in particular synchrotron radiation based X-ray tomographic microscopy (SRXTM), but also 3Helium Magnetic Resonance Imaging, as well as the stereological estimation of the number of alveoli and the length of the free septal edge. First, the most important new finding may be the following: alveolarization of the lung does not cease after the maturation of the alveolar microvasculature but continues until young adulthood and, even more important, maybe reactivated lifelong if needed to rescue structural damages of the lungs. Second, the pulmonary acinus represents the functional unit of the lung. Because the borders of the acini could not be detected in classical histological sections, any investigation of the acini requires 3-dimensional (imaging) methods. Based on SRXTM it was shown that in rat lungs the number of acini stays constant, meaning that their volume increases by a factor of ~ 11 after birth. The latter is very important for acinar ventilation and particle deposition."
  • Sonic Hedgehog Signaling Regulates Myofibroblast Function during Alveolar Septum Formation in Murine Postnatal Lung[2] "Sonic Hedgehog (Shh) signaling regulates mesenchymal proliferation and differentiation during embryonic lung development. In the adult lung, Shh signaling maintains mesenchymal quiescence and is dysregulated in diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Our previous data implicated a role for Shh in postnatal lung development. Here, we report a detailed analysis of Shh signaling during murine postnatal lung development. We show that Shh pathway expression and activity during alveolarization (postnatal day [P] 0-P14) are distinct from those during maturation (P14-P24). This biphasic pattern is paralleled by the transient presence of Gli1+;α-smooth muscle actin (α-SMA)+ myofibroblasts in the growing alveolar septal tips. Carefully timed inhibition of Hedgehog (Hh) signaling during alveolarization defined mechanisms by which Shh influences the mesenchymal compartment. First, interruption of Hh signaling at earlier time points results in increased lung compliance and wall structure defects of increasing severity, ranging from moderately enlarged alveolar airspaces to markedly enlarged airspaces and fewer secondary septa. Second, Shh signaling is required for myofibroblast differentiation: Hh inhibition during early alveolarization almost completely eliminates Gli1+;α-SMA+ cells at the septal tips, and Gli1-lineage tracing revealed that Gli1+ cells do not undergo apoptosis after Hh inhibition but remain in the alveolar septa and are unable to express α-SMA. Third, Shh signaling is vital to mesenchymal proliferation during alveolarization, as Hh inhibition decreased proliferation of Gli1+ cells and their progeny. Our study establishes Shh as a new alveolarization-promoting factor that might be affected in perinatal lung diseases that are associated with impaired alveolarization."
  • Lung growth in infants and toddlers assessed by multi-slice computed tomography[3] "Our in vivo assessment suggests that growth of the lung parenchyma in infants and toddlers occurred with a constant relationship between air volume and lung tissue, which is consistent with lung growth occurring primarily by the addition of alveoli, rather than expansion of alveoli."
  • Lung parenchyma at maturity is influenced by postnatal growth but not by moderate preterm birth in sheep[4] "Our data suggest that moderate preterm birth (sheep born 14 days before term) does not cause persistent alterations in lung parenchyma. However, slow postnatal growth in low-birth-weight sheep results in smaller lungs with fewer alveoli and a lower alveolar surface area relative to body weight."
More recent papers  
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Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

Lung - Alveolar Stage

Alveolar sac structure
  • The postnatal lung, with alveoli forming.
  • Expansion of gas exchange alveoli, vascular beds (capillaries), lymphatics and innervation.
  • Very premature infants will still be at the earlier Saccular stage.

Preterm Saccular Stage

  • week 24 to near term.
  • most peripheral airways form widened "airspaces", termed saccules.
  • saccules widen and lengthen the airspace (by the addition of new generations).
  • future gas exchange region expands significantly.
  • Fibroblastic cells also undergo differentiation, they produce extracellular matrix, collagen, and elastin.
    • May have a role in epithelial differentiation and control of surfactant secretion.
  • 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.
  • Thyroid hormone required for differentiation and stimulate surfactant production.
Links: Principal stages of lung development in humans

Alveolar Cells

Alveoli
Alveolar sac structure

Alveolar Type I cells

  • small alveolar cells, type I pneumocytes
  • very flat cells (thin as 0.05 µm)
  • form most of the surface of the alveolar walls
  • may contribute epithelium on both faces of the alveolar wall

Alveolar Type II cells

  • large alveolar cells, type II pneumocytes
  • irregular to cuboidal shaped cells
  • contain large number of granules called lamellar bodies, these are the precursors to pulmonary surfactant (phospholipid mixture).
  • end month 6 alveolar cells type 2 appear and begin to secrete surfactant - premature babies have difficulties associated with insufficient surfactant.

Alveolar Macrophages

  • remove particulate matter that enters the alveoli with inspired air
  • migrate over alveolar epithelium and phagocytose particulate matter
Respiratory histology 02.jpg

Alveoli and Duct

Respiratory histology 04.jpg

Alveoli elastin

Alveoli Number

  • 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
  • after birth alveoli form by septal subdivision of the large gas-exchange saccules.
Postnatal alveoli number
Age (months) Alveoli (million) Respiratory Airways (million) Generations of Airways
Birth 24 1.5
3 86 1.8
3 77 2.5 21
3 73 2.0
7 112 3.7
13 129 4.5 22
16 127 4.7
22 160 7.1
48 257 7.9
98 280 14.0 23
Adult 296 14.0 23
Data modified from [5]

  Links: respiratory | Respiratory Comparison | Mouse Human Respiratory | Mouse respiratory stages | mouse | rat | rabbit | Timeline Comparisons


The First Breath

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

Exchange of Fluid for Air

  • 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

Lower Respiratory Tract

Bronchiole

Respiratory histology 01.jpg Respiratory histology 09.jpg

Upper Respiratory Tract

Trachea

  • cellular differentiation takes up to 6 months to be complete.
    • most species, epithelial cell differentiation of the trachea usually is not complete until just before birth.
  • more peripheral airway generations the cellular differentiation continues into the early postnatal period.
  • fetal epithelial cells
    • are glycogen-filled cells
    • glycogen gradually replaced with a granular cytoplasm filled with numerous organelles during cellular differentiation.
    • cells are found throughout the tracheobronchial tree and extending into the most peripheral saccules.
  • epithelium gives rise to more than 10 different cell types.

Trachea Histology

Respiratory histology 05.jpg Respiratory histology 06.jpg

Upper Respiratory Tract

Nasal Cavity

Respiratory histology 11.jpg Respiratory histology 12.jpg

Olfactory Epithelium

Respiratory histology 14.jpg Respiratory histology 13.jpg

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

Pleural Cavity

pleura
pleura
  • The anatomical body cavity in which the lungs develop and lie.
  • The pleural cavity forms in the lateral plate mesoderm as part of the early single intraembryonic coelom.
  • This cavity is initially continuous with pericardial and peritoneal cavities and form initially as two narrow canals
    • later becomes separated by folding (pleuropericardial fold, pleuroperitoneal membrane) and the later formation of the diaphragm

pleuropericardial fold - (pleuropericardial membrane) An early embryonic fold which restricts the communication between pleural cavity and pericardiac cavity, contains both the cardinal vein and phrenic nerve.

pleuroperitoneal membrane - An early embryonic membrane that forms inferiorly at the septum transversum to separate peritoneal cavity from pleural cavity.

Pleura

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

Rib Orientation

Rib orientation

Infant Rib

  • lies virtually horizontal
  • allowing diaphragmatic breathing only.

Adult Rib

  • lies oblique (both anterior and lateral views)
  • allows for both pump-handle and bucket handle types of inspiration.

References

  1. 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.
  2. Kugler MC, Loomis CA, Zhao Z, Cushman JC, Liu L & Munger JS. (2017). Sonic Hedgehog Signaling Regulates Myofibroblast Function during Alveolar Septum Formation in Murine Postnatal Lung. Am. J. Respir. Cell Mol. Biol. , 57, 280-293. PMID: 28379718 DOI.
  3. Rao L, Tiller C, Coates C, Kimmel R, Applegate KE, Granroth-Cook J, Denski C, Nguyen J, Yu Z, Hoffman E & Tepper RS. (2010). Lung growth in infants and toddlers assessed by multi-slice computed tomography. Acad Radiol , 17, 1128-35. PMID: 20542449 DOI.
  4. Maritz G, Probyn M, De Matteo R, Snibson K & Harding R. (2008). Lung parenchyma at maturity is influenced by postnatal growth but not by moderate preterm birth in sheep. Neonatology , 93, 28-35. PMID: 17630495 DOI.
  5. Dunnill MS. Postnatal growth of the lung. Thorax 1962;17:329–333.


Reviews

Smith LJ, McKay KO, van Asperen PP, Selvadurai H & Fitzgerald DA. (2010). Normal development of the lung and premature birth. Paediatr Respir Rev , 11, 135-42. PMID: 20692626 DOI.

Hsia CC. (2004). Signals and mechanisms of compensatory lung growth. J. Appl. Physiol. , 97, 1992-8. PMID: 15475557 DOI.

Thurlbeck WM. (1975). Postnatal growth and development of the lung. Am. Rev. Respir. Dis. , 111, 803-44. PMID: 1094872 DOI.

Strang LB. (1977). Growth and development of the lung: fetal and postnatal. Annu. Rev. Physiol. , 39, 253-76. PMID: 139844 DOI.

Articles

Barré SF, Haberthür D, Stampanoni M & Schittny JC. (2014). Efficient estimation of the total number of acini in adult rat lung. Physiol Rep , 2, . PMID: 24997068 DOI.

Mund SI, Stampanoni M & Schittny JC. (2008). Developmental alveolarization of the mouse lung. Dev. Dyn. , 237, 2108-16. PMID: 18651668 DOI.

McGrath-Morrow SA, Cho C, Cho C, Zhen L, Hicklin DJ & Tuder RM. (2005). Vascular endothelial growth factor receptor 2 blockade disrupts postnatal lung development. Am. J. Respir. Cell Mol. Biol. , 32, 420-7. PMID: 15722510 DOI.

Beyea JA, Olson DM & Harvey S. (2005). Growth hormone expression in the perinatal and postnatal rat lung. Dev. Dyn. , 232, 1037-46. PMID: 15736201 DOI.

Hsia CC. (2004). Signals and mechanisms of compensatory lung growth. J. Appl. Physiol. , 97, 1992-8. PMID: 15475557 DOI.

Search PubMed

Search Pubmed: Postnatal Respiratory Development | Postnatal Lung Growth

Terms

  • angiogenesis - the process of formation of new blood vessels from pre-existing blood vessels (capillaries) through sprouting. This mechanism differs from vasculogenesis.
  • antenatal before birth.
  • alveoli number at birth - from 20 - 50 million and eventually in the adult 300 million.
  • blood-air barrier - refers to the region where gas exchange actually takes place in the lung, located where the basement membranes of type I cells and blood capillary endothelial cells are fused.
  • 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.
  • dewatering of the lung - physiological process that occurs at birth where 1. fluid in the upper respiratory tract is expired and 2. fluid in the lower respiratory tract is rapidly absorbed.
  • 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.
  • FEV - Forced Expiratory Volume
  • forced expiratory volume - (FEV) Spirometry term for the fraction of the forced vital capacity that is exhaled in a specific number of seconds. Abbreviated FEV with a subscript indicating how many seconds the measurement lasted.
  • 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.
  • pre-acinar - refers to the non-respiratory portions of the bronchial tree.
  • 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.
  • Spirometry - clinical measure of respiratory airflow.
  • 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 (American Academy of Pediatrics Policy | Canadian Paediatric Society Recommendations)
  • tachypnea - (Greek, rapid breathing) an increased respiratory rate of greater than 60 breaths/minute in a quiet resting baby.
  • 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.
  • vasculogenesis - the process of formation of new blood vessels from differentiating endothelial cells. This mechanism differs from angiogenesis.

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Cite this page: Hill, M.A. (2024, March 19) Embryology Respiratory System - Postnatal. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Respiratory_System_-_Postnatal

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