Histology Respiratory System, for medical students.

Respiratory system histology notes from junqueiras basic histology.

1. THE RESPIRATORY
SYSTEM
-HISTOLOGY NOTES

2. RESPIRATORY SYSTEM FUNCTION
•Facilitates the exchange of oxygen (O2) and carbon dioxide
(CO2) between the blood and external environment.
•Upper Respiratory Tract: Includes nasal cavities, pharynx, and
larynx.
•Lower Respiratory Tract: Comprises the trachea, bronchi,
bronchioles, and terminal bronchioles.

3. •Alveoli: Small, air-filled sacs where the exchange of O2 and CO2
takes place between inspired air and blood.
•Structural Support: Provided by a combination of cartilage, collagen,
elastic fibers, and smooth muscle in the conducting portion, ensuring
rigid support, flexibility, and extensibility.
•Conducting Portion: Cleanses and humidifies inspired air, providing
conduits for air movement. Includes nasal cavities, pharynx, larynx,
trachea, bronchi, bronchioles, and terminal bronchioles.
•Respiratory Portion: Where gas exchange occurs, consisting of
respiratory bronchioles,

4. NASAL CAVITIES
•The left and right nasal cavities each have two components the external,
dilated vestibule and the internal nasal cavity.
•Skin of the nose enters the nares (nostrils) partway into the vestibule and
includes sweat glands, sebaceous glands, and coarse, moist vibrissae
(hairs), which filter out particulate material from inspired air.
•Within the vestibule, the epithelium loses its keratinized nature and
undergoes a transition to typical pseudostratified columnar epithelium
which also lines the nasal cavities.
•The nasal cavities lie within the skull as two cavernous chambers separated
by the osseous nasal septum.

5. •Extending from each lateral wall are three bony shelflike projections
called conchae, or turbinate bones.
•Contains a complex vasculature with capillaries that warm and
humidify inspired air, while secretions from seromucous glands moisturize
and trap air impurities.
•The thin mucus layer produced by these glands and goblet cells serves
to trap particulate and gaseous air impurities that are then removed.
•The secretions also contain immunoglobulin A (IgA) from plasma cells in
the lamina propria.

6. EPITHELIAL TYPES:
•Respiratory Epithelium: Covers the middle and inferior conchae, facilitating
respiration.
•Olfactory Epithelium: Specialized epithelium covering the roof of the nasal
cavities and superior conchae, involved in olfaction (sense of smell).

7. RESPIRATORY EPITHELIUM
•Consists of ciliated pseudostratified columnar epithelium, lining most of the
nasal cavities and conducting portion of the respiratory system.
•Basement Membrane: Thick membrane underlying the respiratory
epithelium, providing structural support.

8. CELL TYPES:-
•Ciliated Columnar Cells:
---Abundant cells with numerous cilia (250-300) on their apical surface,
---responsible for moving mucus and trapped particles.
•Goblet Cells:
---Numerous cells containing mucin glycoprotein granules in their apical domains,
---involved in mucus secretion.
•Brush Cells:
---Less numerous chemosensory receptor cells
---with sparse microvilli on their apical surface,
---resembling gustatory cells and involved in signal transduction.

9. •Small Granule Cells (KulchitskyCells):
---Difficult to distinguish cells with dense core granules,
---part of the diffuse neuroendocrine system (DNES),
---representing about 3% of respiratory epithelium cells.
•Basal Cells:
---Mitotically active stem
---and progenitor cells responsible for producing other epithelial cell types.

10. OLFACTORY EPITHELIUM
•The olfactory chemoreceptors for the sense of smell are located in the
olfactory epithelium,
---a specialized region of the mucous membrane covering the superior
conchae at the roof of the nasal cavity.

11. CELL TYPES:
Olfactory Neurons:
•Bipolar neurons
•with nuclei forming an irregular row near the middle of the epithelium.
•Dendrite end with knoblike swelling containing basal bodies and long cilia projecting into
the overlying aqueous layer.
•Function: Act as chemoreceptors, responding to odoriferous substances by generating
action potentials along axons extending to the brain via the olfactory nerve (cranial
nerve I).
•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
•There they form the olfactory nerve (cranial nerve I) and eventually synapse with neurons
in the olfactory bulb of the brain.

12. SUPPORTING CELLS:
•Structure: Columnar cells
---with narrow bases and broad,
---cylindrical apexes containing nuclei and
---extending microvilli into the fluid layer.
•Function: Provide support to olfactory neurons,
---expressing ion channels to maintain a microenvironment conducive to
olfactory function and survival.

13. BASAL CELLS:
•Structure:
---Small, spherical, or cone-shaped cells
---near the basal lamina.
•Function:
---Serve as stem cells for olfactory neurons and supporting cells
---replacing olfactory neurons every 2-3 months and supporting cells less frequently.
•Lamina Propria of Olfactory Epithelium:
•Serous Glands: Known as the olfactory glands or glands of Bowman,
---these are large serous glands present in the lamina propria.
•Function: Produce a continuous flow of fluid
---that surrounds the olfactory cilia,
---aiding in the access of new odoriferous substances to the olfactory receptors.

14. PARANASAL SINUSES:
•Location: Bilateral cavities found within the frontal, maxillary, ethmoid, and
sphenoid bones of the skull.
•Epithelial Lining: Thinner respiratory epithelium with fewer goblet cells
compared to the nasal cavities.
•Lamina Propria: Contains few small glands and is continuous with the
underlying periosteum.
•Communication with Nasal Cavities: Connected to the nasal cavities
through small openings, allowing the movement of mucus produced in the
sinuses into the nasal passages via the activity of ciliated epithelial cells.

15. THE PHARYNX
Location:
•Nasal cavities open posteriorly into the nasopharynx, which is the first part of the pharynx.
•The nasopharynx is continuous caudally with the oropharynx,
•the posterior part of the oral cavity leading to the larynx and esophagus.
•Nasopharynx: Lined with respiratory epithelium, unlike the stratified squamous epithelium
of the oropharynx.
•Mucosa Contents Medial Pharyngeal Tonsil: Present in the mucosa of the nasopharynx.
•Auditory Tubes: Openings of the two auditory tubes, which connect to each middle ear
cavity, are also located in the nasopharynx mucosa.

16. LARYNX
•Short passage (4 cm ×4 cm) for air
---between the pharynx and the trachea.
•Rigid wall reinforced by hyaline cartilage (thyroid, cricoid, and inferior
arytenoid cartilages) and smaller elastic cartilages (epiglottis, cuneiform,
corniculate, and superior arytenoid cartilages), connected by ligaments.
•Movements of these cartilages by skeletal muscles participate in sound
production during phonation.

17. EPIGLOTTIS:
•Flattened structure projecting from the upper rim of the larynx, serving to
prevent swallowed food or fluid from entering the airway passage.
•Epithelial Lining: Upper (lingual) surface covered with stratified squamous
epithelium;
---laryngeal surface transitions to ciliated pseudostratified columnar
(respiratory) epithelium.
•Mixed mucous and serous glands found in the lamina propria beneath the
epithelium.

18. VESTIBULE AND FOLDS OF THE LARYNX
•Mucosal Projection: Below the epiglottis, the mucosa projects bilaterally into the
lumen with two pairs of folds separated by a narrow space or ventricle.
•Upper Pair (Vestibular Folds):
•Composition: Immovable and partly covered with typical respiratory epithelium
overlying numerous seromucous glands and occasional lymphoid nodules.
•Lower Pair (Vocal Folds or Cords):
•Composition: Covered with nonkeratinized stratified squamous epithelium,
protecting the mucosa from abrasion and desiccation caused by rapid air
movement.

19. Vocal Ligament:
•Dense regular bundle of elastic connective tissue supporting the free edge
of each vocal fold.
Vocalis Muscle:
•Location: Deep to the mucosa,
---comprised of large bundles of striated fibers.
•Function: Allows each vocal fold to be moved.

20. Phonation Process:
•Muscles of the larynx draw the paired vocal folds together,
---narrowing the opening between them, known as the rima glottidis.
•Vibration:
---Air expelled from the lungs causes the adducted vocal folds (cords) to
vibrate, producing sound.
•Sound Modification:
•Factors: Pitch and other qualities of sound are altered by changing tension
on the vocal folds, width of the rima glottidis, volume of expelled air, etc.

21. •Resonance:
•Vestibular folds, ventricles, and other structures and spaces higher in the respiratory
tract contribute to the resonance of sound produced in the larynx.
•Speech Production:
•Speech is produced when sounds made in the larynx are modified by movements of
the pharynx, tongue, and lips.
•Sexual Dimorphism:
•Difference: The larynx is larger and the vocal folds longer in males than in females
after puberty, resulting in men typically having a deeper vocal range than women.

22. TRACHEA
•10-12 cm long in adults.
•Lined with typical respiratory mucosa containing numerous seromucous
glands producing watery mucus.
•Structural Features:
•Cartilaginous Rings: A series of about a dozen C-shaped rings of hyaline
cartilage between the submucosa and adventitia reinforce the wall and
maintain the tracheal lumen open.
•Orientation of Cartilage Rings: Open ends of the cartilage rings are on the
posterior surface, against the esophagus, and are bridged by the trachealis
muscle and fibroelastic tissue attached to the perichondrium.

23. •Function of Trachealis Muscle:
•Swallowing: Relaxes during swallowing, allowing the esophagus to bulge into
the tracheal lumen, with the elastic layer preventing excessive distention.
•Cough Reflex: Contracts strongly during the cough reflex, narrowing the
tracheal lumen to increase the velocity of expelled air and facilitate
loosening of material in the air passage.

24. BRONCHIAL TREE & LUNG
•Trachea divides into two primary bronchi, entering each lung at the hilum along
with arteries, veins, and lymphatic vessels.
•Primary Bronchi: Course downward and outward, giving rise to three secondary
(lobar) bronchi in the right lung and two in the left lung, each supplying a pulmonary
lobe.
•Secondary Bronchi: Further divide to form tertiary (segmental) bronchi, with each
supplying a bronchopulmonary segment, approximately 10%-12% of each lung, with
its own connective tissue capsule and blood supply.
•Surgical Resection: Lung segments facilitate specific surgical resection of diseased
lung tissue without affecting nearby healthy tissue.

25. •Tertiary Bronchi to Bronchioles: Tertiary bronchi give rise to smaller bronchi,
eventually forming bronchioles, with terminal bronchioles branching into
pulmonary lobules.
•Pulmonary Lobules: Each pyramid-shaped pulmonary lobule contains five to
seven terminal bronchioles and is delineated by a thin layer of connective
tissue, often incomplete in adults.
•Histological Organization:
•Epithelium and Lamina Propria: As one moves through smaller bronchi and
bronchioles toward the respiratory portion, the histological organization of
both the epithelium and the underlying lamina propria gradually becomes
more simplified

26. BRONCHI
•Each primary bronchus branches repeatedly, with each branch becoming
progressively smaller until it reaches a diameter of 1-2 mm.
•Structurally similar to tracheal mucosa, except for the organization of cartilage and
smooth muscle.
•In primary bronchi, most cartilage rings completely encircle the lumen, gradually
replaced with smaller isolated plates of hyaline cartilage as bronchial diameter
decreases.
•Abundant small mucous and serous glands, with ducts opening into the bronchial
lumen.
•Smooth Muscle and Elastic Fibers: Lamina propria contains crisscrossing bundles of
spirally arranged smooth muscle and elastic fibers, becoming more prominent in
smaller bronchial branches. Contraction of this muscle layer leads to the folded
appearance of bronchial mucosa in histological cross-sections.

27. •Lymphocytes:
•Distribution: Numerous lymphocytes found within the lamina propria and
among epithelial cells.
•Lymphatic Nodules: Present, especially at the branching points of the
bronchial tree.
•Mucosa-Associated Lymphoid Tissue (MALT):
•Abundance: Becomes relatively more abundant as bronchi become smaller
and cartilage and other connective tissue are reduced.

28. EPITHELIUM OF
TERMINAL BRONCHIOLES:
•The terminal bronchioles are a crucial part of the lower respiratory tract, serving as both
conducting and respiratory portions of the airway.
•The cuboidal epithelium lining the terminal bronchioles consists mainly of two cell types:
Club cells (formerly known as Clara cells):
•These non-ciliated, rounded cells secrete a non-sticky, proteinaceous compound. Their
functions include:
•Surfactant production: Club cells contribute to the production of surfactant, which
reduces tension in the narrow airway lumen.
•Detoxification: They help detoxify inhaled xenobiotic compounds using enzymes from the
smooth endoplasmic reticulum (SER).
•Local immune defense: Club cells secrete antimicrobial peptides and cytokines to
protect against infections.

29. •Chemosensory brush cells: These cells are also present in the terminal
bronchiole epithelium.
•DNES (Diffuse Neuroendocrine System) small granule cells: Similar to those
found in higher respiratory system epithelium.
•Additionally, a small population of stem cells exists to replace other
bronchiolar cell types.

30. Bronchiolar Lamina Propria:
•Contains elastic fibers and smooth muscle.
•These components contribute to the folding of the mucosa.
•Muscular contraction in both bronchi and bronchioles is primarily controlled
by autonomic nervous system nerves.

31. ASTHMA:
•Common condition caused by chronic inflammation within the bronchial tree of the lungs.
•Characterized by sudden constrictions of the smooth muscle in bronchioles, known as
bronchospasms or bronchial spasms.
•Constriction triggered by mast cell degranulation in response to specific antigens.
Symptoms:
•Resulting difficulty in breathing can range from mild to severe.
Treatment:
•Epinephrine and other sympathomimetic drugs relax the muscle and increase bronchiole diameter
by stimulating the sympathetic nervous system.
•Administered during asthma attacks to alleviate symptoms.
•Comparison of Bronchial and Bronchiolar Walls:
•Proportionately greater muscle layer thickness observed in bronchiolar walls compared to
bronchial walls.

32. RESPIRATORY BRONCHIOLES
•Terminal bronchioles subdivide into two or more respiratory bronchioles.
•Always include saclike alveoli, marking the beginning of the respiratory
region of the system.
•Resembles that of terminal bronchioles but includes a few openings to
alveoli for gas exchange.
•Comprised of smooth muscle and elastic connective tissue.
•Club cells predominant, with simple squamous cells at alveolar openings
extending into the alveolus.
•Alveoli become more numerous and closer together as one proceeds
distally along the respiratory bronchioles.

33. ALVEOLAR DUCTS:
•Distal ends of respiratory bronchioles branch into tubes known as alveolar ducts.
•Completely lined by openings of alveoli, facilitating gas exchange.
•Lined with extremely attenuated squamous cells.
•Thin lamina propria comprises a strand of smooth muscle cells surrounding each
alveolar opening.
•Network of elastic and collagen fibers supports both the duct and its alveoli.
•Larger clusters of alveoli formed at the ends of alveolar ducts, occurring
occasionally along their length.
•Lamina propria becomes extremely thin, consisting essentially of a web of elastic
and reticular fibers encircling the alveolar openings and surrounding each alveolus
closely.
•Network of capillaries surrounds each alveolus, facilitating gas exchange.

34. ALVEOLI
•Saclike evaginations, approximately 200 μm in diameter, originating from
respiratory bronchioles, alveolar ducts, and alveolar sacs.
•Responsible for the spongy structure of the lungs.
•Each adult lung contains approximately 200 million alveoli, providing a total
internal surface area of 75 m^2.
•Resemble small rounded pouches open on one side to an alveolar duct or
alveolar sac.
•Facilitate gas exchange between air and blood through thin specialized
alveolar walls.

35. INTERALVEOLAR SEPTA:
•Thin partitions between neighboring alveoli, consisting of scattered fibroblasts and
sparse extracellular matrix (ECM), including elastic and reticular fibers.
•Elastic fibers enable alveoli to expand with inspiration and contract with expiration,
while reticular fibers prevent collapse and excessive distention.
•Richly vascularized with the richest capillary networks in the body.
•Respiratory Membrane or Blood-Air Barrier:
Composed of:
•Highly attenuated, thin cells lining the alveolus.
•Fused basal laminae of these cells and endothelial cells of capillaries.
•Thin capillary endothelial cells.
•Total thickness varies from 0.1 to 1.5 μm, facilitating efficient gas exchange.

36. •Alveolar Pores (of Kohn):
•Ranging 10-15 μm in diameter, penetrate interalveolar septa and connect
neighboring alveoli opening to different bronchioles.
•Equalize air pressure in alveoli and permit collateral circulation of air if a
bronchiole becomes obstructed.
•Gas Exchange:
•Oxygen (O2) from alveolar air diffuses into capillary blood and binds
hemoglobin in erythrocytes.
•Carbon dioxide (CO2) diffuses into alveolar air from pulmonary blood, with
most CO2 arriving in the lungs as part of H2CO3 inside erythrocytes and
being liberated through the action of carbonic anhydrase.

37. •Capillary Endothelial Cells:
•Very thin but continuous, not fenestrated.
•Perinuclear clustering of most organelles allows the rest of the cell to become very
thin, facilitating highly efficient gas exchange.
•Flattened portions of the cell exhibit numerous pinocytotic vesicles.
•Type I Alveolar Cells (Type I Pneumocytes):
•Extremely attenuated cells lining the alveolar surfaces.
•Constitute about 95% of the alveolar lining.
•Organelles are grouped around the nucleus, reducing the thickness of the
remaining cytoplasm at the blood-air barrier to as little as 25 nm.
•Pinocytotic vesicles in the attenuated cytoplasm may play a role in the turnover of
surfactant and the removal of small particulate contaminants from the outer
surface.
•Tight junctions prevent the leakage of tissue fluid into the alveolar air space.

38. TYPE II ALVEOLAR CELLS
•(Type II Pneumocytes or Septal Cells):
•Cuboidal cells bulging into the air space, interspersed among type I alveolar
cells and bound to them with tight junctions and desmosomes.
•Often occur in groups of two or three at points where two or more alveolar
walls unite.
•Rest on the same basal lamina and have the same origin as type I cells.
•Nuclei are rounded with possible nucleoli, and cytoplasm is lightly stained
with many vesicles.

39. •Lamellar Bodies:
•Structures found in type II alveolar cells, revealed by TEM to be membrane-
bound granules 100-400 nm in diameter containing closely stacked parallel
membrane lamellae.
•Contain a variety of lipids, phospholipids, and proteins, continuously
synthesized and released at the apical cell surface.
•Function:
•Act as pulmonary surfactant by spreading over the entire inner alveolar
surface as a complex film of phospholipids and lipoproteins over a thin
aqueous phase at the cell membranes.
•Lowers surface tension at the air-epithelium interface, preventing alveolar
collapse at exhalation and allowing alveoli to be inflated with less inspiratory
force, thereby easing the work of breathing.

40. •Components of Surfactant Layer:
•Phospholipid dipalmitoylphosphatidylcholine(DPPC).
•Cholesterol.
•Four surfactant proteins:
•Surfactant protein A (SP-A) and SP-D, important for innate immune protection within alveoli.
•SP-B and SP-C, hydrophobic membrane proteins required for proper orientation of DPPC in the
surfactant film lining the alveolus.
•Surfactant Turnover:
•Constant turnover, gradually removed by pinocytosis in both types of alveolar cells and by
macrophages.
•Fetal Development:
•Surfactant appears in the last weeks of gestation as type II cells differentiate and form lamellar
bodies.
•Lack of adequate surfactant is a major cause of respiratory distress in premature neonates.

41. ALVEOLAR MACROPHAGES (DUST CELLS):
•Found in alveoli and interalveolar septum.
•Tens of millions of monocytes migrate daily from microvasculature into lung
tissue.
•Phagocytose erythrocytes lost from damaged capillaries and airborne
particulate matter that reaches alveoli.
•Active alveolar macrophages appear slightly darker due to dust, carbon,
and complexed iron (hemosiderin) content.
•Filled macrophages have various fates: migrate into bronchioles, exit lungs
via lymphatic drainage, or remain in interalveolar septa connective tissue.

42. •Removal of Alveolar Lining Fluids:
•Conducting passages remove alveolar lining fluids via ciliary activity.
•Secretions combine with bronchial mucus to form bronchoalveolar fluid,
aiding in the removal of particulate components from inspired air.
•Composition of Bronchoalveolar Fluid:
•Bacteriostatic, containing lysozyme and other protective agents produced
by club cells, type II alveolar cells, and alveolar macrophages.

43. REGENERATION IN THE ALVEOLAR LINING:
•Inhalation of toxic gases or similar materials can kill type I and II cells lining
pulmonary alveoli.
•Death of alveolar cells triggers mitotic activity in the remaining type II cells.
•Progeny of type II cells become progenitors for both cell types.
•Normal turnover rate of type II cells is estimated at 1% per day, resulting in
continuous renewal of alveolar cells.
•Increased toxic stress stimulates stem cells to divide, giving rise to new
alveolar cell progenitors.

44. •Lung Vascular Circulation:
•Pulmonary circulation: Carries O2-depleted blood for gas exchange.
•Bronchial circulation: Carries O2-rich blood.
•Pulmonary arteries and veins have relatively thin walls due to low pressures.
•Pulmonary arteries branch and accompany the bronchial tree, forming dense
capillary networks around alveoli.
•Lung Vasculature:
•Venules from capillary networks are found in lung parenchyma.
•Bronchial arteries enter lung hilum, branching along with bronchial tree to distribute
blood.
•Bronchial arteries anastomose with branches of pulmonary artery at level of
respiratory bronchioles.

45. •Lymphatic Drainage:
•Lymphatic vessels originate in bronchioles, draining into lymph nodes near hilum.
•Deep lymphatic network parallels superficial network in visceral pleura.
•Nerve Innervation:
•Both parasympathetic and sympathetic autonomic fibers innervate lungs.
•Control reflexes regulating smooth muscle contractions determining airway
diameters.
•General visceral afferent fibers also present, carrying poorly localized pain
sensations.
•Nerves primarily found in connective tissue surrounding larger bronchial elements,
exiting lung at hilum.

46. MEDICAL APPLICATION: EMPHYSEMA:
•Chronic lung disease often caused by smoking.
•Involves dilation and permanent enlargement of bronchioles.
•Accompanied by loss of cells in alveoli and other airway walls, leading to
irreversible loss of respiratory function.
•Infections in lung regions can lead to pneumonia.

47. PLEURAL MEMBRANES:
•Serous membrane covering lung's outer surface and internal thoracic cavity
wall.
•Visceral pleura: Attached to lung tissue.
•Parietal pleura: Lines thoracic walls.
•Both layers composed of simple squamous mesothelial cells on thin
connective tissue layer with collagen and elastic fibers.
•Elastic fibers of visceral pleura continuous with those of pulmonary
parenchyma.

48. •Pleural Cavity:
•Narrow space between parietal and visceral layers.
•Lined with mesothelial cells producing thin film of serous fluid.
•Serous fluid acts as lubricant, facilitating smooth sliding during respiratory
movements.
•Pathological Conditions:
•Pleural cavity may contain liquid or air in certain pathologic states.
•Serosa of pleural cavity is water-permeable.
•Fluid exuded from blood plasma can accumulate as pleural effusion during
inflammation and other abnormal conditions.

49. PNEUMOTHORAX:
•Partial or complete lung collapse due to air trapped in pleural cavity.
•Typically caused by blunt or penetrating chest trauma.
•Symptoms include shortness of breath and hypoxia.
•Pleuritis or Pleurisy:
Inflammation of pleura.
•Commonly caused by acute viral infection or pneumonia.
•Symptoms include chest pain, difficulty breathing.
•Pleural Effusion:
Fluid buildup in pleural cavity.
•Can result from inflamed pleura.
•Symptoms include shortness of breath.

50. •Inhalation:
•Contraction of external intercostal muscles elevates ribs.
•Contraction of diaphragm lowers bottom of thoracic cavity.
•Increases thoracic cavity diameter, resulting in pulmonary expansion.
•Bronchi and bronchioles increase in diameter and length.
•Respiratory portion enlarges, mainly due to expansion of alveolar ducts.
•Elastic fibers of pulmonary parenchyma are stretched.
•Exhalation:
•Lungs retract passively due to muscle relaxation.
•Elastic fibers return to unstretched condition.

51. Squamous Cell Carcinoma:
Often correlated with a history of smoking.
Arises from epithelial cells of segmental bronchi.
Adenocarcinoma:
Most common lung cancer in nonsmokers.
Arises from epithelial cells more peripherally, in bronchioles and alveoli.
Small Cell Carcinoma:
Less common but highly malignant.
Develops from neoplastic transformation of small granule Kulchitskycells in
bronchial respiratory epithelium.