The document summarizes the histology of the respiratory system. It describes the major divisions of the conducting and respiratory portions. The conducting portion includes structures like the nasal cavities and trachea lined with respiratory epithelium. The respiratory portion includes respiratory bronchioles and alveoli where gas exchange occurs. Alveoli are surrounded by interalveolar septa and lined by type I and II pneumocytes. Type II cells secrete pulmonary surfactant to prevent alveolar collapse. Capillaries in the septa are separated from alveolar air by the blood-air barrier to enable gas exchange.

1. PULMONARY
HISTOLOGY

2. Divisions of the Respiratory System
• The conducting portion, which consists of the nasal cavities,
nasopharynx, larynx, trachea, bronchi, bronchioles, and terminal
bronchioles
• The respiratory portion, where the system's main function of gas
exchange occurs, consisting of respiratory bronchioles, alveolar
ducts, and alveoli
• Most of the nasal cavities and the respiratory system's conducting
portion is lined with mucosa having ciliated pseudostratified columnar
epithelium commonly known as respiratory epithelium

4. Respiratory Epithelium
• Respiratory epithelium is the classic example of pseudostratified ciliated columnar
epithelium.
• Usually rests on a very thick basement membrane (BM) and has several cell
types, some columnar, some basal, and all contacting the basement membrane.
• Ciliated columnar cells are most abundant, with hundreds of long robust cilia on
each of their bulging apical ends that provide a lush cover of cilia on the luminal
surface.
• Most of the small rounded cells at the basement membrane are stem cells and
their differentiating progeny, which together make up about 30% of the epithelium.
• Mucus-secreting goblet cells (G) and intraepithelial lymphocytes and dendritic
cells are also present in respiratory epithelium.
• The lamina propria is well-vascularized

5. The olfactory mucosa is a pseudostratified epithelium, containing basal stem cells
and columnar support cells in addition to the bipolar olfactory neurons. The
dendrites of these neurons are at the luminal ends and have cilia specialized with
many membrane receptors for odor molecules.

6. Lamina Propria
Basal Cells
Olfactory Neurons
Supporting Cells
Cilia
Mucus

7. 3 Cells of Olfactory Epithelium
• Olfactory neurons are bipolar neurons present throughout this
epithelium. Their nuclei form an irregular row near the middle of this
thick epithelium. The apical (luminal) pole of each olfactory cell is its
dendrite end and has a knoblike swelling with about a dozen basal
bodies. The axons leave the epithelium and unite in the lamina
propria as very small nerves that then pass to the brain through
foramina in the cribriform plate of the ethmoid bone.
• Supporting cells are columnar, with broad, cylindrical apexes
containing the nuclei and narrower bases. On their free surface are
microvilli submerged in a fluid layer. Well-developed junctional
complexes bind the supporting cells to the olfactory cells.
• Basal cells are small, spherical or cone-shaped cells near the basal
lamina. These are the stem cells for the other two types, replacing the
olfactory neurons every 2 to 3 months and support cells less
frequently.

8. The lamina propria of the olfactory
epithelium possesses large serous
glands, the olfactory glands (of Bowman),
which produce a constant flow of fluid
surrounding the olfactory cilia and
facilitating the access of new odoriferous
substances.

9. Larynx

10. Larynx
• Below the epiglottis and laryngeal vestibule, the mucosa projects into
the lumen bilaterally with two pairs of folds separated by a narrow
space.
• The upper immovable vestibular folds are partly covered with typical
pseudostratified respiratory epithelium overlying numerous
seromucous glands and occasional lymphoid nodules.
• The lower vocal folds have features important for phonation or sound
production:
• Stratified squamous epithelium protects the mucosa from abrasion and desiccation
from rapid air movement.
• A dense regular bundle of elastic connective tissue, the vocal ligament, supports the
free edge of each vocal fold.
• Deep to the mucosa of each vocal fold are large bundles of striated fibers that
comprise the vocalis muscle.

11. The state of contraction of the vocalis
muscle and other muscles of the larynx
regulates the width of space between the
vocal folds and thus sound production

12. Trachea

13. Trachea
• The trachea is lined with typical respiratory mucosa in which the
lamina propria contains numerous seromucous glands producing
watery mucus.
• A series with about a dozen C-shaped rings of hyaline cartilage in the
submucosa reinforces the wall and keeps the tracheal lumen open.
• The open ends are bridged by a bundle of smooth muscle called the
trachealis muscle and a sheet of fibroelastic tissue attached to the
perichondrium.
• The entire organ is surrounded by adventitia.

14. Trachealis Muscle
• The trachealis muscle relaxes during swallowing to facilitate the
passage of food.
• The muscle strongly contracts in the cough reflex to narrow the
tracheal lumen and provide for increased velocity of the expelled air
and better loosening of material in the air passage.

15. Bronchi

16. Intrapulmonary Bronchi
• The mucosa of the larger bronchi is structurally similar to the tracheal
mucosa except for the organization of cartilage and smooth muscle.
• In the extrapulmonary (primary) bronchi most cartilage rings
completely encircle the lumen, but as the bronchial diameter
decreases, cartilage rings are gradually replaced with isolated plates
of hyaline cartilage.
• Small mucous and serous glands are abundant, with ducts opening
into the bronchial lumen.
• The lamina propria also contains crisscrossing bundles of spirally
arranged smooth muscle and elastic fibers which become more
prominent in the smaller bronchial branches.

17. Bronchial Wall

18. Bronchioles

19. Bronchioles
• Bronchioles are typically designated as the intralobular airways with
diameters of 1 mm or less, formed after about the 10th generation of
branching
• They lack both mucosal glands and cartilage
• The epithelium decreases in height and complexity to become ciliated
simple columnar or simple cuboidal epithelium
• The ciliated epithelial lining of bronchioles begins the mucociliary
apparatus or escalator, important in clearing debris and mucus by
moving it upward along the bronchial tree and trachea.

20. Clara Cells

21. Clara Cells
• Most numerous in the cuboidal epithelium of terminal bronchioles are
Clara cells, or exocrine bronchiolar cells, which have nonciliated,
dome-shaped apical ends with secretory granules.
• Functions
• Secretion of surfactant lipoproteins and mucins on the epithelial surface
• Detoxification of inhaled xenobiotic compounds by enzymes of the SER
• Secretion of antimicrobial peptides and cytokines for local immune defense
• In a stem cell subpopulation, injury-induced mitosis for replacement of the
other bronchiolar cell types.

22. Respiratory Bronchioles
• Each terminal bronchiole subdivides into two or more respiratory
bronchioles that include saclike alveoli and represent the first-part
respiratory region of this organ system.
• The respiratory bronchiolar mucosa is structurally identical to that of
the terminal bronchioles, except for a few openings to the alveoli
where gas exchange occurs.
• The mucosa lining consists of Clara cells and ciliated cuboidal cells,
with simple squamous cells at the alveolar openings and extending
into the alveolus.
• Proceeding distally along the respiratory bronchioles, alveoli are more
numerous and closer together.
• Smooth muscle and elastic connective tissue make up the lamina
propria.

23. Bernoulli’s Principle
• Bernoulli’s Principle
• As air moves faster, the pressure decreases
• As air moves slower, pressure increases
• Since the total cross sectional area of the respiratory tract actually
increases due to branching in parallel bronchioles, the air velocity is
slower within each bronchiole
• Low speed of air  less need for reinforcement  less cartilage
• The higher pressure prevents collapse of airways, whereas in areas
like the trachea, high speeds=low pressure and cartilage is needed
for reinforcement.

24. Alveoli

25. Alveoli
• Distal ends of respiratory bronchioles branch into tubes called alveolar
ducts that are completely lined by the openings of alveoli. Both the
alveolar ducts and the alveoli themselves are lined with extremely
attenuated squamous cells.
• Each alveolus resembles a small rounded pouch open on one side to an
alveolar duct or alveolar sac.
• Between neighboring alveoli lie thin interalveolar septa consisting of
scattered fibroblasts and sparse extracellular matrix (ECM), notably
elastic and reticular fibers, of connective tissue.
• The arrangement of elastic fibers enables alveoli to expand with
inspiration and contract passively with expiration; reticular fibers prevent
both collapse and excessive distention of alveoli.
• The interalveolar septa are vascularized with the richest capillary
networks in the body

27. Blood Air Barrier
• Air in the alveoli is separated from capillary blood by three
components referred to collectively as the respiratory
membrane or blood-air barrier.
• Two to three highly attenuated, thin cells lining the alveolus
• Type I and II Pneumocytes
• The fused basal laminae of alveoli and capillary
• The thin endothelial cells of the capillary.

29. Type I Alveolar Cells
• Type I alveolar cells are attenuated cells that line alveolar surfaces.
• Maintain the alveolar side of the blood-air barrier and cover about
95% of the alveolar surface.
• These cells are so thin that the TEM was needed to prove that all
alveoli have an epithelial lining
• Organelles are grouped around the nucleus, reducing the thickness of
the cytoplasm at the blood-air barrier to as little as 25 nm.
• In addition to desmosomes, all type I epithelial cells have occluding
junctions that prevent the leakage of tissue fluid into the alveolar air
space

30. Type II

31. Type II Alveolar Cells
• Cuboidal cells that bulge into the air space (2-5%) of alveolar surface
• Type II cells divide to replace their own population after injury and to
provide progenitor cells for the type I cell population.
• Nuclei are rounded and cytoplasm is typically lightly stained with
many vesicles.
• Many vesicles of type II alveolar cells are lamellar bodies, which
contain various lipids, phospholipids, and proteins that are
continuously synthesized and released at the apical cell surface
• Acts as pulmonary surfactant.
• The surfactant film lowers surface tension at the air-epithelium
interface, which helps prevent alveolar collapse at exhalation and
allows alveoli to be inflated with less inspiratory force, easing the work
of breathing.

32. Alveolar Macrophages
• Alveolar macrophages, also called dust cells, are found in alveoli and
in the interalveolar septum
• Active macrophages in alveoli can often be distinguished from type II
pneumocytes because they are slightly darker due to their content of
dust and carbon from air and complexed iron (hemosiderin) from
erythrocytes

33. Vascular Networks
• 1) Pulmonary circulation, carrying O2-depleted blood
• 2) Bronchial circulation, carrying systemic, nutrient-rich blood.
• The pulmonary arteries and veins are relatively thin-walled as a result
of the low pressures (25 mm Hg systolic, 5 mm Hg diastolic) within
the pulmonary circuit. Within the lung, the pulmonary artery branches
and accompanies the bronchial tree with its branches sharing the
adventitia of the bronchi and bronchioles.
• Thinner walls, much lower ratio of wall diameter to lumen diameter,
much lower pressure and lower resistance than systemic arteries.
• At the level of the alveolar duct, the branches of this artery form the
dense capillary networks in the interalveolar septa that contact the
alveoli.

34. Overview

36. Mucociliary Clearance and CF
• Cilia of the respiratory epithelium move the mucus blanket towards
the pharynx where it is swallowed or expectorated.
• Goblet cells secrete the blanket of mucus that moistens and collects
particles from the air coming in through the nasal cavity .
• In CF, blockage of the chlorine channels prevents secretion of water
and mucous becomes thick and sticky interfering with ciliary motility.

37. Asthma
• Asthma is a common condition produced by chronic inflammation
within the bronchial tree of the lungs. The disorder is characterized by
sudden constrictions of the smooth muscle in bronchioles called
bronchospasms, or bronchial spasms. The resulting difficulty in
breathing can be very mild to severe.
• Epinephrine and other sympathomimetic drugs relax the muscle and
increase the bronchiole diameter by stimulating the sympathetic
nervous system, and they are administered during asthma attacks.
• When the thickness of the bronchial walls is compared with that of the
bronchiolar walls, the bronchiolar muscle layer is seen to be
proportionately greater.

38. Alpha 1 Anti-trypsin and Emphysema
• Elastic fiber damage and loss is the basis of emphysema
• Chronic respiratory exposure to tobacco smoke inhibits alpha1-
antitrypsin, an inhibitor of elastase enzymes (secreted by alveolar
macrophages and neutrophils) that attack elastic tissue
• Emphysema primarily affects respiratory bronchioles and alveoli,
which become expanded and unable to expel air efficiently during
exhalation

39. Infant Respiratory Distress Syndrome
• Infant respiratory distress syndrome, the leading cause of death in
premature babies, is due to incomplete differentiation of type II
alveolar cells and a resulting deficit of surfactant and difficulty in
expanding the alveoli in breathing.
• Treatment involves insertion of an endotracheal tube to provide both
continuous positive airway pressure (CPAP) and exogenous
surfactant, either synthesized chemically or purified from lungs of
cattle.
• STEROIDS WORK TOO…