• Development of the lung can be divided into two phases, lung
growth (structural development)and lung maturation (functional
• As gestation progresses, progressive branching of the airways and
finally development of alveolar spaces capable of gas exchange in the
• The surfactant system, composed of phospholipids that decrease
surfacetension within the alveoli and prevent alveolar collapse during
exhalation, develops in the last trimester,and reaches maturity by
approximately 36 weeks
• Lung development continuous even after birth.
• The alveoli develop in increasing numbers until the age of 8 years and
increase in size until growth of the chest wall is finished.
• The full-term infant, with an estimated 50 million alveoli, has the
potential to add another 250 million alveoli and increase its total
alveolar surface area from approximately 3 to 70 m2 at maturity.
• Lung buds are lined by endodermally derived epithelium which
differentiates into respiratory epithelium that lines the airways and
specialized epithelium that lines the alveoli.
• The innervation of the lungs is derived from ectoderm, while the
mesoderm is the origin of pulmonary blood vessels, smooth muscle,
cartilage and other connective tissue.
PHASES OF LUNG DEVELOPMENT
• Embryonal Phase
• Pseudoglandular Phase
• Canalicular Phase
• Saccular Phase
• Alveolar Phase
EMBRYONAL PHASE(3-6 weeks)
• It starts by formation of a groove in the ventral lower phaynx- Sulcus
laryngotrachealis (28 days)
• The lung begins to emerge as a bud from this goove called the true
lung primordium (30 days)which elongates and forms trachea and
subdivides into two bronchial buds (33days) , which then separates
from the esophagus forming a tracheoesophageal septum.
• The right lung bud is directed caudally and left lung bud more
• Further division leads to formation of 3 buds on right and 2 on left.
They correspond to pulmonary lobes.
• By the end of embryonic phase, segments arise.
• Development progresses in the 8 week old embryo as the lobar buds
• The left and right pulmonary artery and vein develops at about 5
weeks of gestation
• The respiratory epithelium is developed from endoderm referred as
• The diaphragm also develop during the embryonal stage of lung
development. Complete development of diaphragm occurs by
approx. week 7 of gestation.
Pseudoglandular Phase(5-16 weeks)
• Named after the distinct glandular appearance of the developing
lung, extends to week 16 of gestation.
• Air conducting bronchial tree till the terminal bronchiole is set
• Distal strutures are the terminal bronchioles, which later differentiate
into respiratory bronchioles and alveolar ducts.
• Once pattern is laid, the subsequent growth of airways is in size only.
• Differenciation of lung epithelium begins.
• Transition from formation of bronchial epithelial cells (ciliated
columnar and goblet cells) to alveolar type II cells.
STRUCTURE DEVELOPMENT GESTATIONAL AGE
Cilia appears on surface of epithelium of the
trachea and the mainstem bronchi
Goblet cells appears 13 -14weeks
Submucosal glands arises as solid buds from
basal layer of epithelium
The development of cartilage 10-24 weeks
Lymphatics appear 8-10weeks
Canalicular phase( 15-25 weeks)
• The canalization of the mesenchyme by respiratory airways and capillaries.
• Gas exchanging portion of the lung is formed and vascularised.
• Each terminal bronchiole divides into 2 or more respiratory bronchioles-
divide into 3-6 alveolar ducts.
• Remarkable changes in airway epithelium and surounding mesenchyme.
• By 20 weeks, differentiation of the cubic type II pneumocyte into flattened
type I pneumocytes occur.
• Along the acinus in close proximity- invasion of capillaries into mesenchyme-
future gas exchange.
• Appearance of lamellar bodies in type II pneumocytes-surfactant storage.
Saccular phase(24 weeks to term)
• Lung epithelium produces maximum amniotic fluid.
• Type II pneumocytes start to secrete surfactant.
• Clusters of sacs form on the terminal bronchioli. Last generation of
• At birth, these airspaces are called primitive saccule.
• Smooth walled sacculi form at the end of airway lined by type I and II
• Primary septa between the sacculi are thick and contain two network
• Substantial thinning of the interstitium occurs( apoptosis and ongoing
differentiation of mesenchymal cells)
• the interstitial fibroblasts begin the production of ECM in the
interductal and intersaccular space.
• At the end of saccular stage, the lung parenchyma possesses
thick, immature septa that contain a double-layered capillary
Alveolar phase(late fetal period to childhood)
• Begin in the last few weeks of pregnancy.
• The saccules continue to mature following birth.
• The first alveoli are formed from new sacculi.
• Saccules doenot acieve adult configuration until 5 weeks after birth.
• Functioning alveoli- connected to alveolar duct , lined by type I cells,
intimately in contact with pulmonary capillaries.,contain surfactant,
have pores of Kuhn connecting to adjacent alveoli
• Almost 1/3 of the roughly 300 million alveoli are completely
developed at birth.
• By the age of 8, complete dvelopment of 300 million alveoli occurs.
• Lymphatic network is well developed .
• Before birth the alveolar sacculi become increasingly complex
structurally. A large number of small protrusions form along the
• These become larger and subdivide the sacculi into smaller subunits,
the alveoli, which are delimited by secondary septa.
• Formation of new septa within terminal sacs is the mainstep for
differentiation of the terminal saccule into alveoli( Alveolarization)
Lung Stage Weeks Features Vascular
Embryonic week 4 to 5
lung buds originate as an outgrowth from the
ventral wall of the foregut where lobar division
artery then lobular
Pseudoglandular week 5 to 17
Branching has continue form terminal
bronchioles. No respiratory bronchioles oralveoli
week 16 to
Each terminal bronchiole divides into2 or more
repiratory bronchioles, which in turn divideinti
3-6 alveolar ducts.
week 24 to
Terminal sacs (primitive alveoli) form,and
capillaries etablish close contact
late fetal to 8
secondary septation occurs, alveoli increase in
size and number. mature alveoli have well
developed capillary contacts.
• At about 32 days pulmonary trunk appears from truncus arteriosus.
• Pulmonary arteries -6th left aortic arch.This joins the vascular system
that has already formed in the lung bud. Its branches divide in
correspondence with those of the bronchial tree.
• Supernumerary arteries occur with increasing frequency towards the
periphery and supply structures adjacent to the main bronchi and
• Majority of periacinar branches are formed by 16 th week
• 12 wks –conventional and supernumerary branches in the same
• Post natally-upto 18 months, conventional branches increase
• Then supernumerary branches increase till 8 yrs
• in the embryonic period pulmonary venous blood
drains via the splanchnic plexus in to the
primordia of the systemic venous system(cardinal
and umbilico vitelline veins)
• Pulmonary vein develops from the cranial out
pouching of the sinoatrial region of heart
Notas do Editor
Decrease in interstitial tissue and thinning of airspace walls.
hosphatidylinositol (v phosphatidyl choline and phosphatidyl glycerol in late gestation)