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New Lecture notes

Respiratory tree

  • Nasal cavity
  • Conchae (terminus; makes air going turbulent; warming it up and humidifying it; want the air to be 37C when it reaches the lungs)
  • Nasal sinuses (lighten skull, produce resonance in the voice)
  • Pharyngeal tonsils - crypts to catch bacteria etc
  • Coronal section - conchae, sinuses, orbit etc
  • Nasal septum
  • Epithelium in that region is classic respiratory (pseudo stratified ciliated columnar epithelium with goblet cells)
    • Serous glands - secrete watery fluid for washing
  • Some of it is olfactory
    • We're microosmatic - have poor sense of smell - not much olfactory area
      • Damaged by smoking or cocaine use
  • Olfactory bulb, near the cribiform plate of the ethmoid bone
  • Olfactory cells hang down into the nasal cavity
  • These cells keep replacing themselves -- as we get older, stem cell activity is poor, so our sense of smell gets worse
  • Vapour dissolves in the serous solution over the olfactory area, and triggers an action potential to form and take
  • Olfactory epithelium is pseudo stratified columnar epithelium with cilia (file), but NO GOBLET CELLS
  • There are large holes (venous sinuses), which a big blood vessels to keep the area warm. The warmth helps the vapours dissolve in the serous
  • Olfactory nerves take impulse to the olfactory bulbs
  • Bowman's glands (holes with a necklace of cuboidal cells around it) that produce secretions to wash away the dissolved chemicals from old smells; ready to get new smell
  • Sense of smell accommodates - gets used to smells

Larynx

  • Oryngoscope
  • Vocal cord = stratified squamous epithelium
    • Abrasive area
  • Either side = respiratory epithelium
  • Vocal ligament sits beneath a stratified squamous epithelium
  • Men's vocal cords are bigger and looser than women's vocal cords - therefore men's larynxes are bigger to accommodate.
  • Recess of Morgani separates this from the vestibular fold (false vocal cord)

Trachea

  • Anterior part of trachea is covered with C-shaped rings of cartilage, at the back is a trachealis smooth muscle
  • Hyaline cartilage (not fibrous)
  • Glands = mixture of mucus and serous (mixed glands; called tracheal glands)
  • Cartilage has chondrocytes in it
  • Pink/purple = matrix (chemical constituents that the cell makes; chondroitan sulfate, glycosaminoglycans)
  • Perichondrium surrounds the cartilage
  • Poor blood supply for cartilage - if you damage it, it is slow for repair (tendons poor, ligaments better, muscle, good, bone excellent).
  • Collagen after an injury repairs tissue quickly, but it's the wrong type of tissue (e.g. hurt muscle forms scar, then the physio will break up the scar tissue to allow the muscle to regrow
  • Scab gets itchy from tearing on the skin
  • Classical respiratory epithelium - psuedostratified columnar epithelium with cilia and goblet cells

Bronchi

  • As we go down the respiratory tree, cartilage gets less (little blocks of it)
  • Epithelium gets lower in height -- moving away from columnar, down to cuboidal
  • Less goblet cells
  • Less cilia
  • More smooth muscle (important in asthmatics -- in asthma you get bronchoconstriction - stress/cold air etc, body sees it as a major airborne attack. Response: 1. goblet cells produce more mucus (clogging myself up - wheezing) 2. bronchoconstriction (close down the airborne attack)). Then you can't get much air in with the dust, but then you also can't get air out. The body is thinking the right way, but it goes too hard (overzealous).
  • Bronchus has a little cartilage, epithelium is more cuboidal, less cilia, less goblet cells

Bronchioles

  • Exist two types of bronchioles:
    • Respiratory bronchiole
    • Terminal bronchioles
  • Bronchiolitis = inside lungs, bronchitis = outside lung
  • Terminal --> respiratory --> alveolar ducts --> alveolar sacs --> alveoli
  • At the end, cuboidal/squamous epithelium, no cartilage, smooth muscle
  • Bronchioles that OPEN UP = respiratory bronchiole
  • Terminal bronchiole = closed (no branches)

Alveolar ducts, alveoli

  • Alveolar duct = corridor with the alveoli coming off of it
  • Bubbles = smooth muscle
  • Note blood vessels
  • Alveoli form a honeycomb
  • Alveolar cells
    • Lining cell = pneumocyte type 1 (P1 cell); structural cell
    • P2 cell - bigger, rounder and hangs more into the space; make surfactant (reduces the surface tension; then the alveoli don't collapse, so you don't have to use heaps of energy breathing)
    • Macrophages (dust cells) - come from blood monocytes.
  • Capillaries
  • Macrophages --> kupffer cells in liver, langerhans cells in skin cell, osteocytes
    • Pseudopods with omoeboid movement
    • Full of hydrolases and phosphatases
  • Macrophages pick up carbon, silicone etc - can't dissolve it, so they keep it inside themselves
  • Mesothelioma = aggressive form of lung cancer, due to sharp asbestos fibres that puncture cells in the lung
    • Fibreglass is similar (e.g. pink batts)
  • People who work in coal mines get black lungs
  • Surfactant can be seen under the microscope
  • Stain for carbon, can see in the macrophage
  • Blood vessels run alongside the airways
  • Cartilage = bronchus. No cartilage = bronchiole.
  • Pulmonary embolism can come from a DVT
  • Lung is lined by pleura
  • Pleura is made of squamous cells (??)

See also

PDP notes

Subdivisions

  1. Air conducting zone is a series of tubes for moving air in and out of the lungs. Includes the nasal cavities, pharynx, larynx, trachea, bronchi, and bronchioles. Functions: warming or cooling inspired air (by capillary beds, nasal venous plexuses), moistening, and detoxification by absorbing harmful gases (e.g. ozone, SO2), trapping harmful bacteria and viruses (via Goblet cell and mucous/serous gland secretions) and removing particulate matter (via cilia).
  2. Respiratory portion: gas exchange occurs across the alveolar wall.
  3. A musculo-elastic ventilation apparatus e.g. intercostals and diaphragm, and elastic fibres for the recoil of the lungs in expiration.

Nasal cavities

Divided into several distinct regions:

  1. Vestibule, restricted to the nostrils lined by stratified squamous epithelium. Its opening into the respiratory cavity is guarded by stiff hairs (vibrissae), which are associated with sebaceous glands.
  2. Respiratory area, occupying most of the cavity, is separated from the oral cavity by the hard and soft palates. It is lined with pseudostratified columnar ciliated epithelium. Its lateral surface has 3 bony shelves (superior, middle and inferior conchae/tubinates). The lamina propria contains venous plexuses that warm or cool inspired air.
  3. Paranasal sinuses (frontal, maxillary, sphenoid, ethmoid) drain into the nasal cavity. They are lined by pseudostratified ciliated columnar epithelium continuous with the epithelium of the nasal cavity. Sinuses humidify air in the nasal cavity and act as voice resonators.
  4. Olfactory area is limited to the narrow roof of the nasal cavities and extends over the superior concha and onto the adjacent septum. The olfactory epithelium is similar to the respiratory epithelium except that it lacks goblet cells, its columnar cells are taller, and with less cilia. Olfactory cells are bipolar neurons. Their apices form small bulbs, the olfactory vesicles, from which emerge 6-10 long, non-motile cilia (olfactory hairs), which function as odor receptors. The basal segments of the neurons narrow to become efferent axons, which form small bundles, the fila olfactoria, which pass through the cribriform plate of the ethmoid bone to synapse with neurons in the olfactory bulb. For smell, the olfactory epithelium must be moistened by serous secretions of Bowman's glands in the lamina propria.

Nasopharynx

The superior part of the nasopharynx is continuous with the nasal cavity anteriorly. Respiratory epithelium lines most of its cavity except in areas where epithelial surfaces e.g. uvula and soft palate contact the posterior wall of the nasopharynx during swallowing (epithelium here is stratified squamous non keratinising).

Larynx

Connects the pharynx above with the trachea below. It is a bilateral chamber whose walls are a series of cartilages. The larynx is held together by ligaments and moved by skeletal muscles. An extrinsic group of muscles acts to change the position of the larynx as a whole (swallowing). Smaller intrinsic muscles alter the position of the vocal cords (folds) for sound. Two single cartilages (thyroid and cricoid), and the triangular arytenoids are hyaline cartilage. The smaller, internal cartilages, the corniculates (horn shaped) and cuneiforms (wedge-shaped); the epiglottis, and the tips of the arytenoids are elastic cartilage. Bordering the rima inferiorly are the true vocal cords covered with stratified squamous epithelium. The cords consist of bundles of elastic fibres, the vocal ligaments, and the voluntary vocalis muscle. These vary the tension and length of the cords. Above the junction are the false vocal cords (protective, ventricular folds), which are separated from the true cords by the ventricle. The false cords have no muscle but have mixed seromucous glands and are covered by respiratory epithelium.

Trachea and primary bronchi

These airways have similar histological features and functions. In cross section they have 4 layers:

  1. Mucosa: epithelium is respiratory (pseudostratified columnar ciliated with goblet cells) and a lamina propria infiltrated with lymphocytes in a meshwork of elastic and reticular fibres.
  2. Submucosa contains loose CT and mixed serous and mucous glands.
  3. Muscularis contains the involuntary trachealis smooth muscle that fills the intervals between the open rings in the trachea. This allows some movement of the trachea and changing shape during swallowing.
  4. Adventitia contains collagenous CT bands, and C-shaped hyaline cartilage rings (16-20 in trachea; 8-10 broken rings in each bronchus).

Intrapulmonary bronchi

As the right primary (extrapulmonary) bronchus enters the lung, it divides into 3 intrapulmonary (secondary) bronchi, one for each lobe. The left lung receives 2 from the left bronchus. They continue to undergo branching, resulting in segmental (tertiary) bronchi that supply each of the bronchopulmonary segments. The secondary and tertiary bronchi have the same general histological patterns as the primary bronchi. Differences develop as the bronchi become smaller: 1) the cartilage rings are reduced to irregular plates of cartilage. 2) A circular band of smooth muscle develops between the cartilage plates and the mucosa. 3) Less Goblet cells. 4) The epithelium is reduced in height and becomes simple columnar with fewer cilia.

Bronchioles

Two bronchioles (diam 0.5-1 mm) arise from the final branching of a tertiary bronchus. Histological features of bronchioles are: 1) absence of cartilaginous plates, 2) increase in size of the circular smooth muscle, 3) nonciliated Clara (bronchiolar epithelial cells) cells 4) epithelial reduction from ciliated columnar in the larger bronchioles to ciliated or nonciliated low cuboidal in the terminal segment 5) only the larger bronchioles have mucoserous glands in the lamina propria 6) lack of goblet cells.

  • The final bifurcation of a bronchiole are terminal bronchioles (final air passageways of the conduction zone), which show reduction in the muscle layer beneath the epithelium, and the lamina propria is thin. The epithelium is reduced to simple cuboidal; many are ciliated, others are nonciliated Clara cells.

Respiratory zone

Respiratory bronchiole

Each terminal bronchiole divides into 2 or more respiratory bronchioles. The mucosa of the latter is similar to the lining of the terminal bronchiole except that the wall is interrupted by respiratory alveoli. Other features are tags of smooth muscle between the alveoli and elastic fibres in the walls of the alveoli. The bronchiolar epithelium is continuous with the flat, alveolar epithelium lining each alveolus. Clara cells are abundant.

Alveolar ducts and sacs

Each respiratory bronchiole divides into several alveolar ducts whose walls consist entirely of alveolar openings. Remnants of the muscle layer are seen as a thin ring of tissue surrounding the openings of the alveoli. As an alveolar duct becomes wider in its distal segment, it terminates in a cluster of alveoli sharing a common chamber (alveolar sac).

Alveoli

The functional unit of the lung has the side next to the lumen missing, allowing access of inspired air. Alveoli are thin-walled outpocketings of the respiratory bronchioles, alveolar ducts and alveolar sacs. In the ducts and sacs, they are tightly wedged together and share thin common walls, (alveolar septa). The alveolar wall has a capillary lined with flat endothelial cells.

Lining cells of the alveolus

  1. Type 1 pneumocytes are small epithelial squamous cells. They line about 95% of the alveolar surface area.
  2. Type 2 pneumocytes are cuboidal alveolar cells. Under EM, there are lamellated inclusion bodies involved with the production of surfactant. Surfactant is crucial to the function of the neonatal lung mainly because:
    • Its high viscosity and low surface tension stabilise the diameter of the alveoli and prevent their collapse after each expiration
    • Because the alveoli remain partially open, they are expanded on inspiration with much less expenditure of energy.
  3. Macrophages (dust cells) are large cells, which lie free in the alveoli and the air passageways. The dust cells clean the lungs of invading bacteria and particulate matter, such as carbon and other dust-borne debris.

Pleura

A double-layered serous, mesothelial membrane enveloping both lungs as the visceral pleura and lining the internal surface of the thoracic cavity as the parietal pleura. These 2 layers are continuous at the hilum of each lung forming 2 closed sacs (pleural cavities). Each sac is lined with mesothelium containing a thin film of fluid that lubricates the lung and pleural cavity surfaces during respiration. The pleura also consists of a layer of fibroelastic CT with fibroblasts, macrophages, capillaries and lymphatics.

Old notes

NOTE: check the relevant prac information on the SH page for more information on this histology lecture.

Introduction

  • Respiratory tract function:
    • Gas exchange
      • Providing oxygen for cells and removing carbon dioxide generated through respiration

Morphological subdivisions

  • Air conducting zone
    • Tubes that move air in and out of the lungs
      • Made up of the – nasal cavities, pharynx, larynx, trachea, bronchi and bronchioles ending at the terminal bronchioles
    • Improves the quality of inspired air
      • Warming/cooling – capillary beds, nasal venous plexuses
      • Moistening
      • Detoxifying by absorption of harmful gases (ozone, SO2)
      • Entrapment of harmful bacteria and viruses (Goblet cell and mucous/serous gland secretions)
      • Cleansing – removal of particulate matter (cilia)
  • Respiratory portion
    • Gas exchange occurs through thin-walled alveoli
      • Alveoli appear in airways distal to terminal bronchioles
  • Musculo-elastic ventilation apparatus
    • Muscles of respiration
      • Eg: intercostals, diaphragm
    • Elastic fibres – provide elastic recoil of the lungs in expiration

Nasal cavities

  • Divided into 4 regions
    • Vestibule
      • Narrow – in the nostrils
      • Lined by stratified squamous epithelium
        • An extension of the upper lip
      • External opening is lined by short, stiff hair (vibrissae) – have sebaceous glands
    • Respiratory area
      • Most of the cavity, lined by hard and soft palates
      • Lined by pseudostratified columnar ciliated epithelium with goblet cells (respiratory epithelium)
        • Ie the Schneiderian membrane
      • Has a medial and lateral surface
        • Medial surface (septal) is smooth
        • Lateral surface has three overhanging shelves of bone –superior, middle, inferior conchae
    • (otherwise known as turbinates)
      • Beneath the respiratory epithelium (especially on the larger conchae_ there is an extensive lamina propria with thin-walled venous plexuses for warming the air
    • Paranasal sinuses (frontal, maxillary, sphenoidal, ethmoidal)
      • In bones – draining into the nasal cavity
      • Lined by pseudostratified ciliated columnar epithelium continuous with nasal cavity lining
  • Thin lamina propria is attached to periosteum and has some seromucous glands
    • Secretions from these glands and goblet cells are swept into the cavity by cilia
      • Function: humidify air and resonate the voice
    • Olfactory area
      • Narrow roof of the nasal cavity extending over the superior concha and the adjacent septum
      • Epithelium resembles respiratory epithelium without the goblet cells
        • Pseudostratified columnar cells are taller with less cilia and an indistinct basal lamina

Olfactory epithelium

  • Three cell types:
    • Sustentacular (supporting) cell – tall with long, slender microvilli on its tip
      • Covered in serous fluid
  • Fluid removes odiferous substances in preparation for new ones
    • Basal cells – small, rounded/cone shaped, single layer sitting on basal lamina
      • Undifferentiated stem cells that produce support cells and sensory cells
    • Olfactory/sensory cells – bipolar neuron wedged between basal and sustentacular cells
      • Spindle shaped cells with a lightly stained central nucleus
      • Apices are dilated into bulbs – olfactory vesicles
        • Vesicles extend to the surface between sustentacular cells
          • Each vesicle gives rise to 6-10 long, non-motile cilia (olfactory hairs) that lie on the mucosal surface
            • Odor receptors
        • Basal segments narrow into axons and form bundles (fila olfactoria)
          • These pass through the cribriform plate of the ethmoid bone and synapse with neurons in the olfactory bulb
      • For olfaction, epithelium has to be kept moist by serous secretions
        • Produced by Bowman’s glands in the lamina propria
      • In olfaction, small chemicals dissolve in the secretion causing an action potential that is transmitted to the olfactory bulb and is associated with memory etc

Nasopharynx

  • Superiorly extends into the nasal cavity
  • Respiratory epithelium lines most of this cavity
    • Exceptions: areas where epithelial surfaces are frequently in contact
      • Where the uvula and soft palate contact the posterior nasopharynx during swallowing
      • Here, there is stratified squamous non keratinising epithelium

Larynx

  • Connects the pharynx to the trachea
  • A hollow, bilaterally symmetrical chamber
    • Walls are made of rigid, irregularly shaped cartilages
    • Held together by ligaments, moved by skeletal muscle
      • Extrinsic muscles change the position of the larynx – swallowing
      • Intrinsic muscles alter the relative position of the vocal folds to produce sound
  • Cartilage:
    • Hyaline cartilage:
      • External: thyroid and cricoid and the body of the triangular arytenoids
      • Internal: corniculates (horn shaped) and cuneiforms (wedged shaped)
    • Elastic cartilage:
      • The epiglottis, the tips of the arytenoids
  • Central, midline cavity is the vestibule
    • Lateral extensions of the central cavity are ventricles
  • Central cavity at the vocal cords is called the rima glottis
    • Lined by the true vocal cords
      • Covered in stratified squamous epithelium
      • Made up of bundles of elastic fibres – vocal ligaments
      • Contains the voluntary vocalis muscle which can vary the tension and length of the cords
    • Above the cavity are the false vocal cords (protective, ventricular folds)
      • Separated by the ventricle from the true cords
      • No muscle
      • Rich in seromucous glands and covered in respiratory epithelium

Trachea and primary bronchi

  • Four layers
    • Mucosa
      • Respiratory epithelium
      • Prominent lamina propria containing lymphocytes in a matrix of elastic and reticular fibers
    • Submucosa
      • Loose CT with mixed serous and mucous glands
  • Ducts penetrate the mucosa to reach the lumen
    • Muscularis
      • Contains the involuntary trachealis smooth muscle that fills the open rings in the trachea and join the partial rings in the primary bronchi
    • Adventitia – dense
      • Contains thick collagenous CT bands with C/U-shaped hyaline cartilage
  • 16-20 in the trachea, 8-10 broken in each bronchus
  • An intermediate between bone and cartilage – avascular made up of chondrocytes
    • Pathology:
      • Smooth muscle in the lower bronchi can undergo bronchospasm involving a constriction of the airways
  • Goblet cells undergo hypersecretion further reducing lumen size

Intrapulmonary bronchi

  • Extrapulmonary (primary) bronchi pierce the lung and divide into R: 3, L:2 intrapumonary (secondary) bronchi
    • These secondary bronchi undergo branching as they enter the lung forming segmental (tertiary) bronchi
      • These supply bronchopulmonary segments (R:10, L:8-10)
    • Secondary and tertiary bronchi have the same histology as the primary bronchi
  • As bronchi decrease in size, changes develop:
    • Cartilage rings reduce to irregular cartilage plates and then reduce in size and number as the lumen decreases
    • Smooth muscle layer forms between the cartilage plates and mucosa
    • Goblet cells becomes less numerous
    • Epithelium is reduced in height and becomes simple columnar with fewer cilia

Bronchioles

  • Tertiary bronchi terminate by forming two large bronchioles (0.5-1mm diameter)
    • Features:
      • Lack cartilage
      • Increase in size relative to the smooth muscle layers
      • Many non-ciliated Clara (bronchiolar epithelial cells) cells
      • Epithelial reduction from ciliated columnar to ciliated or non-ciliated low cuboidal in the terminal areas
      • Mucoserous glands in the lamina propria
      • Lack of goblet cells
    • Final bifurcation of bronchioles is forms terminal bronchioles (final part of air conduction zone)
      • Reduction in the muscle layer
      • Thin lamina propria
      • Epithelium is simple cuboidal with some ciliated, others non-ciliated Clara cells
      • Appear as a complete ring histologically

Respiratory bronchiole

  • Transitional structure that separates conduction zone from the respiratory zone
    • At least two respiratory bronchioles divide from each terminal bronchiole
      • Mucosa is similar to terminal bronchioles but has respiratory alveoli
      • Has prominent tags of smooth muscle piercing the alveoli
      • Alveoli:
        • Prominent elastic fibres
        • Epithelium is continuous with the bronchiolar epithelium
        • Abundant Clara cells
      • Histologically identifiable by the long or junction tubes

Alveolar ducts and sacs

  • Respiratory bronchioles divide into alveolar ducts
    • Walls are entirely made up of alveolar openings
      • Alveolar epithelium lines the alveoli and alveolar duct
      • Muscle layer no longer seen, but a thin tissue ring remnant remains
    • As ducts travel distally they become wider and terminate in a cluster of alveoli sharing a common chamber(alveolar sac)

Alveoli

  • Functional unit of the lung
    • Missing the side net to the lumen allowing inspired air inside
  • Thin-walled, outpocketings of respiratory bronchioles, alveolar ducts and alveolar sacs
    • Ducts and sacs are tightly clumped together and have common walls – alveolar septa
  • Each alveoli has a capillary lined with flat endothelial cells and a continuous basal lamina
  • Alveolus cells:
    • Type 1 Pneumocytes
      • Small alveolar epithelial (septal) squamous cells
      • Line 95% of alveolar surface area (only 40 % of alveolar cells are these however)
      • Have a flattened, central nucleus with broad, thin, winglike cytoplasm extension (0.1-0.3μm thick)
    • Type 2 Pneumocytes
      • Large alveolar cells (granular)
      • More numerous (60%) but are cuboidal cells without cytoplasmic extensions
        • Occupy 5% of alveolar surface
      • Lamellated inclusion bodies with microvilli
        • Lamellated bodies produce surfactant that contributes to the alveoli lumen
    • Surfactant stabilises the alveolar surface
    • Surfactant
      • Highly viscous and has low surface tension
        • Allows the alveoli diameter to stabilise and not collapse after expiration at birth
    • Thus air remains in the lungs and the residual capacity is established
      • Thus, if the alveoli remain open, less energy is required to expand them and the newborn can breathe easier
    • Macrophages (dust cells)
      • Large cells, 10-12 μm diameter
      • Lie in the alveoli and lumen (move around on pseudopods)
      • Clean the lungs of invading bacteria and particulate matter (eg: carbon, dust-borne debris)
        • Deficiencies/malfunction in macrophages increases virulence of pulmonary disorders
          • Eg: pulmonary tuberculosis, emphysema
        • The garbage collectors of the human body
      • Contain phosphotases and have the ability o hydrolyse particles/foreign bodies
        • If macrophages take up lead, silicon, asbestos, carbon – deposits can be seen in the lungs

Blood vessels

  • Lungs have a dual blood supply
    • Functional (pulmonary arteries)
      • Less pressure than systemic arteries
      • Arteries and veins are histologically similar
      • Vessels accompany the bronchi and bronchioles
        • Supernumery arteries leave pulmonary arteries and travel directly to the alveoli and outer lung tissue
    • Important ancillary route minimising physiological insult (eg. embolism)
    • Nutritive (bronchial arteries - branches of the aorta)
      • Accompany and nourish the bronchi, terminal bronchioles and lung CT
      • Anastomose with the pulmonary circulation at the conducting/respiratory passage junction
        • Smaller diameter and thinner walls than pulmonary arteries
      • Bronchial veins follow larger bronchioles and bronchi to the root of the lung and empty into the azygos/pulmonary veins
      • Chronic inflammation/neoplasia can result in larger and more bronchial arteries

Pleura

  • Double-layered, serous, mesothelial membrane
    • Visceral pleura envelopes the lungs
    • Parietal pleura lines the internal surface of the thoracic cavity
  • These layers are continuous at the hilum of each lung and form closed sacs (pleural cavities)
    • Sac is lined with mesothelium and contains fluid that lubricates the lung and pleural cavity
      • Allows frictionless movement during respiration
  • Also has a layer of fibroelastic CT containing fibroblasts, macrophages, capillaries and lymphatics

Embryonic lung development

  • Embryonic stage (2-7 weeks)
    • Respiratory diverticulum and bronchopulmonary segments
  • Pseudoglandular stage (8-16 weeks)
    • Growth of duct system in the bronchopulmonary segments
    • Gland-like lungs
  • Canalicular stage (17-26 weeks)
    • Formation of respiratory bronchioles and blood vessel growth
  • Terminal sac stage (26weeks-birth)
    • Alveoli bud
    • Epithelial lining differentiates into two types
      • P1 (gas exchange),
      • P2 (surfactant, from 32 weeks)
  • Postnatal stage
    • 90% of alveoli are formed after birth