Lecture - Respiratory Development

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Introduction

adult lungs

The respiratory system does not carry out its physiological function (of gas exchange) until after birth. The respiratory tract, diaphragm and lungs do form early in embryonic development.

The respiratory tract is divided anatomically into 2 main parts:

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


Lecture Objectives

lung structure
alveoli and blood vessels
  • Understanding of embryonic lung development
  • Understanding of the stages of lung development
  • Understanding of diaphragm development
  • Brief understanding of respiratory vascular development
  • Brief understanding of respiratory abnormalities
  • Brief understanding of molecular mechanisms

Lecture Date: 2013-09-03 Lecture Time: 16:00 Venue: Biomed E Speaker: Steve Palmer

The Powerpoint file used to present this lecture is available as a pdf document HERE

The audio will be available via the Lectopia system through Blackboard


Textbooks

The Developing Human: Clinically Oriented Embryology

The Developing Human, 9th edn.jpg Citation: The Developing Human: clinically oriented embryology 9th ed. Keith L. Moore, T.V.N. Persaud, Mark G. Torchia. Philadelphia, PA: Saunders, 2011.

Larsen's Human Embryology

Larsen's human embryology 4th edn.jpg Citation: Larsen's human embryology 4th ed. Schoenwolf, Gary C; Larsen, William J, (William James). Philadelphia, PA : Elsevier/Churchill Livingstone, c2009.

UNSW Embryology

Logo.png Hill, M.A. (2012) UNSW Embryology (12th ed.). Sydney:UNSW.
Respiratory Links: Introduction | Science Lecture | Med Lecture | Stage 13 | Stage 22 | Upper Respiratory Tract | Diaphragm | Histology | Postnatal | Abnormalities | Respiratory Quiz | Category:Respiratory
Historic Embryology
1902 The Nasal Cavities and Olfactory Structures | 1912 Upper Respiratory Tract | 1912 Respiratory | 1918 Respiratory images | 1921 Respiratory | 1922 Chick Pulmonary Vessels


Developmental Overview

Week 5 Respiratory Development

Lung Development

  • week 4 - 5 embryonic
  • week 5 - 17 pseudoglandular
  • week 16 - 25 canalicular
  • week 24 - 40 terminal sac
  • late fetal - 8 years alveolar

Germ Layers

  • Endoderm and splanchnic mesoderm form majority of conducting and alveoli.
  • Ectoderm will contribute the neural innervation.
  • Mesoderm also contributes the supporting musculoskeletal components.

Events

  • Week 4 - laryngotracheal groove forms on floor foregut.
  • Week 5 - left and right lung buds push into the pericardioperitoneal canals (primordia of pleural cavity)
  • Week 6 - descent of heart and lungs into thorax. Pleuroperitoneal foramen closes.
  • Week 7 - enlargement of liver stops descent of heart and lungs.
  • Month 3-6 - lungs appear glandular, end month 6 alveolar cells type 2 appear and begin to secrete surfactant.
  • Month 7 - respiratory bronchioles proliferate and end in alveolar ducts and sacs.

Lung Development Stages

Lung alveoli development cartoon.jpg

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

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

Embryonic

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

Pseudoglandular stage

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

Canalicular stage

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

Saccular stage

Alveolar sac structure
  • week 24 to near term.
  • most peripheral airways form widened "airspaces", termed saccules.
  • saccules widen and lengthen the airspace (by the addition of new generations).
  • future gas exchange region expands significantly.
  • Fibroblastic cells also undergo differentiation, they produce extracellular matrix, collagen, and elastin.
    • May have a role in epithelial differentiation and control of surfactant secretion.
  • The vascular tree also grows in length and diameter during this time.

Foregut development

Foregut cartoon

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

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

Upper respiratory tract

Adult upper respiratory tract conducting system
  • part of foregut development
  • anatomically the nose, nasal cavity and the pharynx
  • the pharynx forms a major arched cavity within the pharyngeal arches

MH - pharyngeal arches will be described in head development lecture

Lower respiratory tract

Lung development stage13-22.jpg Stage 22 image 171.jpg

Lung alveoli development cartoon
Fetal lung histology
  • lung buds ( endoderm epithelial tubes) grow/push into mesenchyme covered with pleural cells (lung border)
  • generates a tree-like network by repeated:
  1. elongation
  2. terminal bifurcation
  3. lateral budding
  • The lungs go through an embryonic and 4 distinct histological phases of development

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)
  • pseudoglandular - week 5 - 17 (stage 22 above)
  • canalicular - week 16 - 25
  • terminal sac - week 24 - 40
  • alveolar - late fetal - 8 years (Latin, alveus = cavity or hollow)


Fetal lung volume

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

Weeks (gestational) Volume (ml)
12 to 13 0.05
19 to 22 0.5
29 to 32 1.9

Pleural Cavity

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

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

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


Pleura

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

Diaphragm

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

adult diaphragm

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

Pulmonary Circulation

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

Fetal

Fetal Respiratory Movements

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

The First Breath

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

The exchange of lung fluid for air leads to:

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

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

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

Rib Orientation

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

Respiratory Tract Abnormalities

Respiratory System - Abnormalities

Tracheoesophageal Fistula

(Tracheo-Oesophageal Fistula, Oesophageal Atresia) - Oesophageal Atresia with or without tracheo-oesophageal fistula

Lobar Emphysema (Overinflated Lung)

  1. There is an overinflated left upper lobe
  2. There is a collapsed lower lobe
  3. The left lung is herniating across the mediastinum

Congenital Diaphragmatic Hernia

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.

Azygos Lobe

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

  • 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).

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.
  • Subsequent ingestion by the fetus and damage to respiratory function.
  • Damage to placental vessels meconium myonecrosis may also occur.

Newborn Respiratory Distress Syndrome

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.

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Cite this page: Hill, M.A. (2014) Embryology Lecture - Respiratory Development. Retrieved August 28, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Respiratory_Development

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© Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G


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