Respiratory

systeM

Sylvia Santos
■ Nasal mucosa, Paranasal air sinuses– lined
by pseudostratified ciliated columnar
epithelium/ respiratory epithelium
Olfactory Mucosa of the Nasal Cavity
■ Olfactory epithelium consists of bipolar neurons – olfactory
cells, supporting cells, basal (stem) cells and brush cells
(with microvilli)
■ Supporting cells – similar to neuroglial cells, mechanical and
metabolic support. Also synthesize odorant-binding proteins
■ Brush cells are in synaptic contact with Trigeminal nerve –
carry general sensory information
■ Olfactory glands (Bowman’s glands) in olfactory mucosa –
branched tubuloalveolar serous glands. Secretions also serve
as trap and solvent for odoriferous substances
■ Olfactory receptor cells/ neurons have a lifespan of about 1
month. If injured, they are quickly replaced. Olfactory
receptor cells (and some neurons of the enteric division of
the autonomic nervous system) appear to be the only neurons
in the nervous system that are readily replaced during
postnatal life.
Olfactory Mucosa of the Nasal Cavity
Olfactory Mucosa of the Nasal Cavity
 Larynx
■ Larynx – lined by
respiratory epithelium,
except true vocal cords
(and epiglottis ) lined by
stratified squamous non-
keratinised epithelium.

■ To protect from abrasion

caused by moving air
stream.
TRACHEA
Trachea
■ Thin-walled fibro-cartilaginous tube.

■ Trachea and extrapulmonary bronchi have a

framework of incomplete rings of hyaline
cartilage united by fibrous tissue and
smooth muscle.
Trachea
■ Structure
✔ Mucosa
✔ Submucosa
✔ Cartilaginous layer
✔ Adventitia
Trachea
 Trachea

Serous
glands
Trachea
■ Mucosa
✔ Lined by pseudostratified columnar ciliated epithelium with
goblet cells. Thick basement membrane; thicker in chronic
coughing
✔ Epithelium contains 3 common cell types
-Goblet cells- secrete mucus that entraps dust and other
foreign particles
-Ciliated cells - Entrapped particles are swayed away by cilia
(Mucociliary escalator)
-Basal cells -give rise to new cells
-Brush cells and Kulchitsky cells– present in small numbers

✔ Lamina propria contains connective tissue fibers and diffuse

lymphatic tissue (BALT)
Trachea
■ Submucosa
✔ Lies deep to the mucosa
✔ Elastic membrane between mucosa and
submucosa
✔ Unlike that of most organs – made up of
loose connective tissue
✔ Contains mucous and serous tracheal
glands, BALT
Trachea
■ Hyaline cartilage layer (16-20 C shaped cartilage)
✔ Surrounded by perichondrium
✔ Perichondrium has outer fibrous and inner
chondrogenic layers
✔ Chondrocytes lies in lacunae
✔ Chondrocytes - cell nest
✔ Matrix is basophilic contains collagen fibers and
mucopolysaccharides

✔ In posterior part of trachea, the cartilage is

deficient and is completed by smooth muscles
(trachealis) with fibroelastic tissue.

✔ Cartilage maintains patency .

Trachea
■ Adventitia
✔ Outermost layer of connective tissue made
up of collagen and elastic fibers, trachealis
muscles
Trachea
LUNGS
Lungs
■ Lungs is covered by pleura which is lined by
mesothelium.

■ Principal bronchus (similar to trachea

histologically) enters the lungs.

■ Conducting portion of the lung – intrapulmonary

bronchi , bronchioles , and their different order
of branching up to terminal bronchiole

■ Respiratory portion – respiratory bronchioles,

alveolar ducts , alveolar sacs and alveoli.
Bronchial tree
■ Conducting part
✔ Primary (principal) bronchi
✔ Secondary (lobar) bronchi
✔ Tertiary (segmental) bronchi
✔ Bronchiole
✔ Terminal bronchiole

■ Respiratory part (for gas

exchange)
✔ Respiratory bronchioles
✔ Alveolar duct
✔ Alveolar sacs
✔ Alveoli (~300 million)
Bronchial tree
Lung
 Intrapulmonary bronchi
■ Pseudostratified ciliated
columnar epithelium with
goblet cells
■ Lamina propria contains
elastic fibers and
lymphatic tissue
■ Smooth muscle fibers
surrounds the lamina
propria
■ Submucous has seromucous
bronchial glands
■ Hyaline cartilage rings are
replaced by cartilage
plates
■ Cartilage plates surrounds
the bronchus
■ Bronchi subdivide into
bronchioles
Intrapulmonary bronchi
■ Layers :
✔ Mucosa
✔ Muscularis
✔ Submucosa
✔ Cartilage layer
✔ Adventitia
Bronchioles
■ Air conducting ducts that measure less than 1mm or less in
diameter.
■ The large diameter bronchioles initially have a ciliated,
pseudostratified columnar epithelium that gradually
transforms into a simple columnar ciliated as the duct
narrows
■ These ducts branch repeatedly, giving rise to smaller
terminal bronchioles that also branch.
■ The terminal bronchioles finally give rise to the respiratory
bronchioles.

■ The bronchioles are tethered (tied) to the lung parenchyma

by elastic tissue, which plays a key role in the stretch and
recoil of the lungs during inhalation and exhalation.
■ From bronchi through bronchioles, structural
changes occur :

■ Cartilage rings give way to plates; cartilage is

absent from bronchioles
■ Epithelium changes from pseudostratified
columnar to cuboidal; cilia and goblet cells
become sparse/ absent (Largest bronchioles
have goblet cells*)
■ Relative amount of smooth muscle increases*
 Terminal bronchiole
■ Lined by simple cuboidal (columnar) with scattered ciliated cells ,
clara cells
■ No cartilage, bronchial glands and goblet cells
■ Mucosa surrounded by smooth muscle fibers
■ Mucosa shows folding due to contraction of smooth muscle
fibers
■ Adventitia surrounds the bronchiole
 Respiratory bronchiole
■ Lined by simple cuboidal epithelium
■ Smooth muscles and connective tissue surrounds the
epithelium
■ Alveoli branching from the walls
■ Transition between the conducting and respiratory
tissues
Alveolar ducts
■ Lined by type one squamous alveolar cells
■ Smooth muscles may be present in the walls
■ Lead to alveolar sacs
■ Supported by elastic and reticular fibers
 Lung Alveoli
■ Evaginations of respiratory bronchioles,
alveolar ducts and alveolar sacs

■ Lined by thin, simple squamous type I

pneumocytes (alveolar epithelial cell)

■ Alveoli are separated by interalveolar

septa

■ Interalveolar connective tissue consists

of collagen and elastic fibres along with
capillaries

■ Alveoli also contains alveolar

macrophages (dust cells), Type II
pneumocytes

■ Type 2 pneumocytes produce

surfactant and contains multilamellar
vesicle which contains precursors of
alveolar surfactant.

■ Brush cells may be present

E – capillary endothelial cell
C – Clara cell
M – alveolar macrophage
Lamellar
bodies
■ Type 2 pneumocytes represents 60% of
cells in the lining epithelium. They retain
the capacity of cell division and can
differentiate into type I pneumocytes in
response to damage to the alveolar lining.
▪ Dust cells
✔ Wandering macrophage, in connective tissue and also alveolar
spaces
✔ Phagocytose the dust particles
✔ Presence of these cells in the sputum is of diagnostic
importance
✔ When these cells are found with phagocytosed RBCs –
Hemoglobin and transferrin converted to hemosiderin –
indicative of Congestive heart failure (– brick red sputum –
the cells also called the heart failure cells)

▪ Interalveolar pores of Kohn

✔ Small apertures lined by epithelium through the
interalveolar septa which link adjacent alveolar cavities.
✔ Allow the flow of air even in the event of blockage of one of
the alveolar ducts.
 Other cells of respiratory tract
■ Ciliated cells
■ Goblet cells – present throughout except in bronchioles
■ Serous cells – simple columnar cells, secrete IgA
■ Clara cells (Club cells): found in terminal and respiratory
bronchioles, produce surfactant, act as stem cells, contain
enzymes-detoxify noxious substances. They are rounded or dome-
shaped non-ciliated cells.
■ Undifferentiated basal cells- these are mitotic stem cells. Most
frequent in larger conducting passages.
■ Intermediate epitheliocytes – nonciliated columnar cells , immature
form of other cells
■ Brush cells – sensory function - chemosensors , absorptive columnar
cells with long stiff microvilli.
■ Kulchitsky cells or argentaffin cells or neuroendocrine cells or small
granule cells : cells are rounded or elliptical , contain granules
(serotonin, calcitonin, bombesin etc), response to hypoxia (O2
sensitive Potassium channels). Involved in regulation of bronchial
secretion, smooth muscle contraction and ciliary action. Present in
groups sometimes – called neuroepithelial bodies
Surfactant
■ Main agent – dipalmitoylphosphatidylcholine (DPPC)
■ Other proteins for structure and function of surfactant –
Surfactant proteins A (SP-A), SP-B, SP-C, SP-D.
■ SP-D participates in a local inflammatory response to acute
lung injury and with SP-A modulates an allergic response to
various inhaled antigens

■ Reduces surface tension in alveloi – thereby prevents

collapse of alveoli during expiration.

■ IRDS (Infant respiratory distress syndrome) – in premature

babies.
■ Surfactant is starting to secrete by 24th week of gestation
Clara cells – CC16
■ Clara cells produce Clara cell secretory protein (CC16) –
abundant component of airway secretion
■ Chronic lung diseases (COPD, asthma) are associated with
changes in abundance of CC16 in airway fluid and serum
(Therefore – pulmonary marker in serum and bronchoalveolar
lavage fluid)
■ Secretion of CC16 into bronchial tree decreases during lung
injury (due to damage to Clara cells), whereas serum levels
may increase because of leakage across the air-blood barrier
Defence Mechanism
■ Overall defense mechanisms of the respiratory system include nasal clearance of
material, which occurs through sneezing, whereas other material may be swept into the
nasopharynx and subsequently swallowed.
■ The mucociliary action within the trachea and bronchi is often called the mucociliary,
or tracheobronchial escalator.
■ At the distal end of the system, the alveolar macrophages phagocytose foreign
material and secrete and respond to an array of cytokines.
■ Neutrophils are attracted by chemokines and factors derived from macrophages and
other cells and phagocytose bacteria.
■ In the bronchi, there is extensive associated lymphoid tissue (BALT),.
■ There are B - and T-cell areas throughout the BALT
■ The B cells synthesize immunoglobulins such as IgA associated with the bronchial
secretion.
■ Helper T cells recognize foreign antigen in association with class II major
histocompatibility complex (MHC) molecules.
■ Cytotoxic T cells recognize fragments of antigen (specifically viral fragments) on the
surface of viral-infected cells in association with class I MHC.
■ Antigen-presenting cells (ie, alveolar macrophages) also function in a similar fashion to
those found elsewhere in the body; they present antigen to helper T cells in
conjunction with class II MHC.
Defence Mechanism
■ IgA functions to prevent attachment of microorganisms to
the epithelium, particularly in the upper respiratory tract
■ IgM and IgG are serum antibodies present in the alveolar
fluid that activate complement by the classic pathway. In
that pathway, fixation of C1 to antibody combined with
antigen leads to activation of C3b, which binds to bacterial
cell walls and enhances opsonization.
■ Neutrophils and macrophages have C3b receptors that
facilitate the opsonization.
■ IgG also functions as an opsonin.
BV – blood vessel
AD – alveolar duct
SM – smooth
muscle
AS – alveolar sacs
S – serous
membrane
Lung
 Squamous metaplasia
■ Squamous metaplasia – respiratory epithelium is replaced by
squamous epithelium
■ Causes – chemical toxins – nicotine of cigarette smoking,
viruses, bacteria

Normal Metaplasia Dysplasia

Dysplasia Dysplasia Carcinoma

Anthracosis
■ Macrophages filled with carbon particles
(coal mine workers, smokers)
 Disorders of Alveoli
■ Lobar pneumonia – caused by
infection (usually Streptococci) –
leading to acute inflammatory
reaction which fills the alveolar
cavities with a mixed fluid/ cellular
exudate.

■ Interstitial fibrosis – as in silicosis

Emphysema
■ Emphysema – progressive
destruction of the alveolar ducts,
sacs and alveoli – leading to permanent
dilatation of air spaces. Loss of elastic tissue, leading to
collapse of bronchioles.
■ Neutrophils enter the lung parenchyma and secrete elevated
levels of elastase, leading to the destruction of the
bronchiolar and alveolar septal elastic tissue support The
destruction of the elasticity in emphysema leads to
diminished breath sounds.
■ There are genetic and environmental causes of emphysema.
The environmental causes include smoking and air pollution,
whereas deficiency in a,1-antitrypsin (antiprotease) activity
is the genetic cause of the disease.
Emphysema
■ The balance between normal elastase-elastin production and
protease-antiprotease activity is altered in emphysema.
Persons with a deficiency in alpha 1-antitrypsin activity lack
sufficient antiprotease activity to counteract neutrophil-
derived elastase.

■ When there is an increase in the entry and activation of

neutrophils in the alveolar space, more elastase is released,
and elastic structures are destroyed,

■ In smoking, there is an increase in the number of neutrophils

and macrophages in alveoli and increased elastase activity
from neutrophils and macrophages.

■ The structures initially targeted in emphysema is alveoli and

alveolar ducts.
Industrial lung disease
■ Silicosis of lungs – in coal
miners, asbestosis
■ Silica in macrophages
present in alveolar septa
may remain for many years
and the silica converted
into silicic acid which
stimulates the
proliferation of fibroblasts
and production of excess
collagen – leads to fibrosis
– pneumosilicosis.
■ These macrophages if
reach the lymph nodes may
cause fibrosis of the
nodes.
Thank you