Histology of Respiratory tract

1. MICROSCOPIC ANATOMY OF
THE RESPIRATORY SYSTEM
OLUWOLE AKINOLA
(Professor & IBRO Fellow)

2. Learning Outcomes
At the end of the lecture, students
should be able to:
• Describe the cellular and histological
organization of the respiratory organs
• Understand the anatomical basis of gas
exchange
• Understand the mechanisms of
respiratory airway protection
• Describe the applied anatomy of the
airway

3. Learning Resources
• Basic Histology, 12th Edition, Anthony Mescher
• Functional Histology
• Other relevant texts

4. Histology of the Pleura • Pleura consists of:
• mesothelium and
• underlying lamina propria
• mesothelium
• Covers the free pleural surface (the aspect
facing pleural cavity)
• It is a layer of squamous cells
• bear some microvilli on their free surfaces
• basal lamina
• A layer of loose connective tissue that supports
mesothelium
• contains fibroblasts, macrophages, abundant
elastic fibres, numerous blood and lymphatic
vessels and nerve fibres
• Resembles peritoneum and serous
pericardium structurally
• Tumour of pleural mesothelium is pleural
mesothelioma
• Could be malignant
• Caused by exposure to asbestos, etc

5. Histology of lower respiratory tract

6. Structure of the Trachea and Extrapulmonary
Bronchi
• Trachea and large bronchi
consist:
• mucosa,
• submucosa,
• hyaline cartilage and
• smooth muscle cells
• Cartilage and muscle cells lie
in a fibrous membrane
• Adventitia
• surrounds trachea and
extrapulmonary bronchi

7. Mucosa of the Trachea
and Large bronchi
• Epithelium:
• ciliated pseudostratified
columnar type
• Goblet cells:
• intersperse the ciliated cells of
the epithelium
• All epithelial cells (ciliated
columnar and goblet cells) are
in contact with underlying
basal lamina
• Ciliary movement
• created by cilia of the columnar
cells,
• drives the overlying mucus
towards the pharynx

8. Mucosa of the Trachea
and Large bronchi
•Lamina Propria:
•external to the
epithelium is the
lamina propria
• a layer of loose
connective tissue
• rich in longitudinally-
disposed elastic fibres
• Also possesses
occasional lymphoid
aggregations

10. Submucosa of the Trachea
• Is of loose connective
tissue.
• lies external to mucosal
lamina propria
• Contains:
• numerous blood vessels,
• nerve fibres and
• scattered lymphoid
tissue
• Possesses some tubular
mucoserous glands

11. Tracheal Cartilages and Smooth Muscle Fibres
• fibrous membrane
• Lies external to submucosa of trachea and
large bronchi
• It is essentially of dense irregular
connective tissue;
• Has collagen and elastic fibres
• 16–20 C-shaped rings of hyaline
cartilage lie within tracheal fibrous
membrane.
• cartilages are arranged one on top of the
other, from above downwards.
• Each is surrounded by perichondrium, and
• is deficient posteriorly .

12. Tracheal Cartilages and
Smooth Muscle Fibres
• Trachealis
• Consists of transversely-disposed smooth
muscle fibres
• Longitudinal smooth muscle fibres are
also found external to the transverse
ones
• Occupy the gaps btw successive rings of
cartilage and between their posterior
ends
• Fxn: Contraction of tracheal and
bronchial smooth muscle fibres
reduces the cross-sectional area of the
airway
• Tracheal hyaline cartilage becomes
increasingly fibrous with age and could
even ossify in old age

13. Tracheal Cartilages and Smooth Muscle Fibres
• The entire tracheal and
bronchial tubes are
surrounded externally
by an adventitia
• A fibrous connective
tissue

14. Structure of the Lung In the substance of each lung are:
• Intrapulmonary air passages of
variable calibres
• bronchi,
• bronchioles,
• alveolar ducts
• Alveolar sacs and alveoli
• associated with the terminal ends
of intrapulmonary air passages
• Connective tissue septa
• that surround air passages,
• and which separate the alveoli
• Branches of pulmonary artery
and tributaries of pulmonary
vns
• These supply the air passages and
alveoli
• Plexuses of blood capillaries
• associated with the alveoli

15. Respiratory Passages
Each lung contains the ff air passages:
• Intrapulmonary bronchi; including:
• terminal parts of lobar bronchi,
• segmental bronchi and
• bronchi of smaller calibres
• Several generations of bronchioles
• These continue distally from the bronchi.
• The smallest and most distal of the
bronchioles are respiratory bronchioles
• Alveolar ducts and atria:
• These continue distally from the respiratory
bronchioles
• Alveolar sac (air saccules),
• that arise from the atria and contain the
alveoli (for gaseous exchange).
• Alveoli are up to 300 million in adults

16. Structure of Intrapulmonary Bronchi • In the lung, intrapulmonary
bronchi divide dichotomously
into generations of smaller
tubes
• Intrapulmonary bronchial wall
consists of
• Mucosa
• Submucosa
• Plates of cartilages
• These are surrounded by
adjoining connective tissue

17. Structure of Intrapulmonary Bronchi
• Mucosa:
• longitudinally ridged
• lined by pseudostratified ciliated columnar
epithelium
• similar to that of extrapulmonary bronchi
• Goblet and Clara cells also intersperse
ciliated epithelial columnar cells
• Clara cells produce surfactant, like alveolar type
II cells
• basal lamina: External to epithelial cells
• lamina propria
• External to basal lamina,
• rich in reticular and elastic fibres
• lamina propria is the most external part of
bronchial mucosa

18. • Submucosa
• Layer of connective tissue
• external to mucosal lamina
propria
• Contains: helical bands of
smooth muscle fibres
• that run in opposite
directions
• Mucous and serous
tubular glands are also
present
• Ducts of these glands traverse
the mucosa to reach the
bronchial lumen
Structure of Intrapulmonary Bronchi

19. Structure of Intrapulmonary Bronchi
• Hyaline cartilage of
intrapulmonary bronchi is
reduced into small plates
• scattered along the bronchial
tubes

20. Bronchitis
• Inflammation of the bronchi
• Could be acute or chronic
• Could be viral or bacterial
• e.g., cause by Haemophilus
influenzae or Streptococcus
pneumoniae
• Swelling of bronchial wall,
narrowing of airway and
congestion occur
• Smoking is a risk factor also
• Is an example of COPD

21. Bronchioles • Structurally, bronchioles are similar to
intrapulmonary bronchi
• but cartilaginous plates are absent
• Bronchiolar Mucosa
• Epithelium: largely ciliated columnar cells,
• Mucosa is folded into longitudinal ridges
• that permit adjustment of bronchiolar diameter
• Goblet cells are absent in bronchial
epithelium, from terminal bronchioles
distally
• Apocrine Clara cells are present also;
• these non-ciliated cells produce proteins that
protect bronchiolar lining against pollutants,
toxins and inflammation.
• They also contribute surfactant
• Similar to type II alveolar cells in fxn

22. • Numerous smooth muscle cells exist
external to the lamina propria of
bronchiolar mucosa
• Contraction of muscle fibres is under
neural and hormonal control
• They relax slightly during inspiration
• contract during expiration.
• Locally released substances such as
serotonin and histamine (from mast
cells) may produce spasm of
bronchiolar wall
Bronchioles, Muscle

23. Terminal Bronchiole
• Is the most distal conductive part of the
bronchioles
• No gaseous exchange occurs here
• owing to the absence of alveoli
• Epithelium:
• ciliated columnar epithelium
• goblet cells
• Clara cells are present
• For surfactant and detoxification
• no cartilage
• Has abundant elastic and smooth
muscle fibres
• Divides into 2-3 respiratory bronchioles
• 3-5 Terminal bronchus are contained in
Secondary lung lobule or Acinus

24. Respiratory Bronchiole
• Branches from terminal bronchiole
• Gives rise to 2–11 alveolar ducts; and
• Supplies primary lobule of the lung
• Bears a few scattered alveoli on its wall
• opposite the side along which the branch of the
pulmonary artery runs
• Epithelium:
• non-ciliated simple cuboidal epithelium
• No goblet cells
• Clara cells present
• Smooth muscle cells and abundant elastic
fibres
• external to the epithelium
• involved in gaseous exchange
• by means of the associated alveoli

25. Alveolar Duct
• Arises from respiratory
bronchiole
• Gives rise to expanded
channels termed atria
• Atria lead into alveolar
sacs,
• which contain many alveoli
• Epithelium:
• a non-ciliated low simple
cuboidal epithelium
• Possesses smooth muscle
cells and elastic fibres in
its wall

26. Alveolar Sacs
and Alveoli
• Alveoli sacs arise from alveolar ducts
• Possess numerous alveoli in their walls.
• Density: About 300 million alveoli found
in adult human lungs
• Network of reticular and elastic fibres
• Supports alveolar sacs and alveoli
• Interalveolar connective tissue septa
• Separate adjacent alveoli
• Blood capillaries
• Capillary Plexuses surround alveoli,
• so are lymph vessels, macrophages and
fibroblasts
• Gas exchange occurs mainly across alveoli
• Following trauma, alveolar cells may be
replaced by connective tissue scar

27. Structure of the
Alveolus
• An alveolus is lined by two types
of epithelial cells:
• type I and type II alveolar epithelia
cells (pneumocytes)
• Type I alveolar epithelia cells
• are the most numerous
• are squamous cells,
• about 0.05 µm in thickness.
• Each has sparse organelles and a
bulging nucleus
• connected to adjacent type I cells
by zonulae adherentes
• Type I alveolar cells have a
lifespan of about 3 weeks

28. • Basement membrane of
alveolar cells and that of
capillary endothelium
form a single continuous
layer
• about 0.1 µm thick.
• Diffusion barrier (air-
blood barrier) between
alveolar air and capillary
blood is just about 0.2
µm across

29. Structure of the
Alveolus
• Type II alveolar epithelial cells
• are rounded and
• rich in organelles and secretory vesicles.
• These cells produce surfactant,
• which reduces alveolar surface tension and
• prevents the alveoli from collapsing during
respiration

30. Alveolar Macrophage (dust cells)
• Are macrophages;
• similar to those of connective tissue.
• migrate to alveoli from adjacent connective tissue
• Functions:
• Remove foreign bodies,
• Involved in inflammatory responses, as in asthma
• engulf red blood cells that enter alveoli in such
conditions as congestive heart failure, etc.
• Thus, they are also called ‘heart failure cells’
• Following phagocytosis of RBC, alveolar
phagocytes appear brick red
• This gives the sputum a brick red colouration,
• which is of diagnostic importance
• Lifespan of alveolar phagocytes is about 4 days

31. Lobules of the Lungs
• Lobules of the lungs
• are functional units of the lung, and
• are of varying sizes
• Millions of Primary and Secondary
lobules exist
• Primary lobule is the smallest
lobule; consists of
• a respiratory bronchiole,
• associated alveolar duct and atria,
• alveolar sacs and alveoli,
• associated blood vessels, lymphatics,
nerve fibres,
• and the surrounding connective tissue

32. Lobules of the Lungs
• Secondary Lobule
• Supplied by a lobular
bronchiole
• That gives rise to 3-5 terminal
bronchioles
• Shape:
• Each lobule is pyramidal,
• the base peripherally directed
and
• the apex towards the hilus
• The base is recognizable on
lung surface as a polygonal
area
• bounded by connective tissue
septa
• the septa separate one lobule
from another

34. Airway Defence Mechanisms
Factors that defend the
airway against infections
include:
• Secretions from goblet
cells and tubular glands
of the airway
• in response to irritation
or neural stimulation
• Ciliary rejection current
(mucocilliary escalaltor),
• in which the current
created by cilia of the
respiratory epithelium
drives particulate matters
(trapped in mucus)
towards the pharynx

35. Airway Defence Mechanisms
• The presence of lysozyme and
immunoglobulin A in the
glandular secretions.
• These prevent bacterial invasion
of the airway.
• Moisturizing effect of the
glands of the airway.
• This protects the airway against
desiccation.
• Forceful removal of particulate
materials in muscular activity
such as coughing

36. • Sensory fibres
from visceral
pleura and lung
receptors reach
the spinal cord
via the
autonomic
pathway
Innervation
of the Lungs

37. Cough Reflex • A protective reflex

38. Additional Clinical
Anatomy of the Lung
• Epithelial cells of the
bronchial tree may be
involved in malignancy
• cigarette smoking is a
risk factor for
bronchogenic
carcinoma
• Cancer cells from the
lungs may metastasize
to bones, suprarenal
glands, liver, and brain
• via the venous and
lymphatic routes

39. Lung Cancer Staging
• Lung cancer could be broadly
categorized into 2:
1. Small cell lung cancer
• Smoking the major risk factor
• More aggressive than NSCLC
• Cancer cells appear small and
rounded under microscope
• May be defined as either limited or
extensive
2. Non-small cell lung cancer
• Includes: adenocarcinoma, squamous
cell carcinoma, large-cell carcinoma
• TNM staging is used in classification
• Less aggressive than small cell lung
cancer
• Lung cancer could spread via lymph
nodes, to adrenal gland, liver, brain,
bones, oesophagus, and other
adjacent and distant structures

40. Lung
Cancer
Staging

41. Additional Clinical
Anatomy of the Lung
• Enlargement of supraclavicular lymph
nodes may be an index of bronchogenic
carcinoma
• Including Small cell lung cancer and NSCLC
• hence, they are called sentinel lymph nodes
• Presence of metastasis in these nodes in
NSCLC is critical as it defines the N status
as N3 (i.e., stage IIIB lung cancer
• i.e., cancer cells have spread as far as
supraclavicular nodes on the same or
opposite side or to opposite thoracic nodes
• Such nodes can only be palpated when
markedly enlarged

42. • Asthma is an inflammatory/ allergic
condition xrised by
• shortness of breath,
• wheezing,
• coughing, etc.
• Results from:
• Spasmic contraction of bronchiolar smooth
myocytes occurs, and
• Inflammatory process resulting in congestion
of the airway (by secretion or oedema of
bronchial mucosa)
• Allergens and non-allergens could trigger
asthma:
• Pollen
• Respiratory viral infection
• Dust and particles and irritants
• Cold air
• Exercise, etc
Additional Clinical Anatomy of the Lung
• Sympathomimetic drugs are
beneficial in asthma
• Beta 2 adrenergic agonists
• e.g., albuterol, levalbuterol, etc.
• Promotes beta2 adrenergic receptor
activity
• Mediates bronchodilation
• Antimuscarinic agents
• e.g., Ipratropium (by aerosol)
• Derivative of atropine
• Blocks muscarinic Ach receptors
• Inhibits bronchoconstriction &
mucus secretion
• Anti-inflammatory drugs
• Corticosteroids:
• Beclomethasone, budesonide, etc
• Theophylline, a methylxanthine
• Relaxes airway smooth muscle
• Taken orally

45. • In bronchoscopy,
carina marks the
beginning of main
bronchi
Bronchoscopy

46. Chronic Obstructive Pulmonary Disease (COPD)
• Chronic bronchitis: Smoking is a risk factor
• Emphysema: Due to deficiency in alpha 1
antitrypsin resulting in damage to lung
parenchyma from the actions of proteases, etc.
• : Smoking is a risk factor
• Mucus cells more in number and activity

47. Emphysema
• Causes shortness of breath
• alveolar elastic tissue is
damaged
• with time, the inner walls of
the alveoli weaken and
rupture
• creating larger air spaces
instead of many small ones
• Cigarrete smoking is a risk
factor
• Emphysema and chronic
bronchitis constitute COPD

48. Pneumonia
• an infection in one or
both lungs
• Caused by bacteria,
viruses, or fungi
• alveoli are inflamed
• They fill with fluid or pus,
• making it difficult to
breathe
• Empyema may occur
• Collection of pus in the
pleural cavity

49. Atelectasis
• the collapse of lung alveoli
• resulting in reduced or absent
gas exchange
• usually unilateral,
• affecting part or all of one lung.
• the alveoli are deflated to
little or no volume,
• as distinct from pulmonary
consolidation, in which they are
filled with liquid
• Could be due to
• surfactant deficiency or
• associated with pneumothorax,
etc.

50. • Cystic fibrosis
• Tuberculosis