RESPIRATORY

Question 1

Mucous layer of the respiratory tract

Answer 1

The respiratory tract

• The pathway through which oxygen enters the body.
• It begins at the nostrils of the nose, continuing into the nasal cavity, passes through the pharynx, larynx, trachea, bronchi, bronchioles and ends in the alveoli.
• The airway as a whole can be divided into two segments:
  
  • Conducting segment (from the nostrils to the terminal bronchiole)
    
    • Cleaning, moistening and warming of the inspired air
  • Respiratory segment (from the respiratory bronchioles to the alveoli).
    
    • Gas exchange

Along the respiratory pathway, the epithelial lining changes to accommodate different functions.

• Main function of respiratory system:

1. Air conduction
2. Air filtration
3. Gas exchange
4. * air passing over larynx is used for speach production

Mucosa of respiratory tract: Conducting segment

1- Tunica mucosa

• Epithelium:
  
  • Stratified squamous epithelium (non keratinized)
    
    • Regions exposed to direct airflow or physical abrasion
      
      • Oropharynx, epiglottis, vocal folds
  • Pseudostratified cilliated columnar epithelium
  • Consits of 5 types of cells:
    
    • Ciliated columnar cells
      
      • Most abundant
      • Each with about 300 cilia on its apical surface
        
        • Display coordinate sweeping movements of cilia
    • Goblet cells
      
      • Dispersed between the ciliated cells
      • Produce mucus, which covers the luminal surface of the conducting portion
    • Brush cells
      
      • ​(chemosensory receptors)
      • Columnar cells
      • Apical surfaces bear short, blunt microvilli and their basal surfaces have afferent nerve endings
    • Small granule cells, Kulchitsky cells
      
      • Cells of the diffuse neuroendorcine system
        
        • They resemble neuroendocrine cells in the GIT.
      • Located on the basement membrane
      • Contain numerous dense core granules in the basal cytoplasm
        
        • Produce serotonin and various peptide hormones.
    • Basal cells
      
      • Small rounded cells on the basement are stem cells that give rise to the other cell types
• The mucocillary complex:
  
  • Ciliary movements continuously propel the sheet of mucus (produced by the goblet cells and mucous cells of glands) with trapped air-borne particulate materials (dust particles) for elimination.
    
    • In smokers the proportion of ciliated and goblet cells is altered; the greater number of goblet cells is involved in clearing the increased particulate and gaseous pollutants.

2- Lamina propria:

• Loose connective tissue
  
  • Rich in cells (fibroblasts, macrophages, lymphocytes, mast cells, and plasma cells)
  • Highly vascularized.
    
    • rich, vascular network that includes a complex set of capillary loops:
    • arrangement of the vessels allows the inhaled air to be warmed by blood flowing through the part of the loop closest to the surface.
• Mucosa associated lymphoid tissue (MALT)
  
  • Diffuse lymphatic infiltration, lymphatic nodules; pharyngeal, tubal and laryngeal tonsils.
• Elastic fibers are abundant
  
  • In the larynx they form vocal ligaments and conus elasticus
    
    • bundle of the longitudinally arranged elastic fibers caudally from the vocal fold.
  • In the trachea and bronchi the layer of the elastic fibers constitutes boundary between the lamina propria and submucosa.
• ​​Mucous and serous secretions play a major role in the conditioning process:
  
  • _​_Small seromucous glands:
    
    • Upper respiratory tract and larynx:
      
      • Located in the lamina propria
    • Trachea and bronchi:
      
      • Submucosa
  • Serous secretions
    
    • Prevent the dehydration of the epithelium by moving air, enable ciliary activity, contain lysozyme, and IgA.
  • Mucous secretions
    
    • ​Trap air-borne particulate materials.
    • Mucus covers almost the entire luminal surface of the conducting passages and is con- tinuously produced by goblet cells and mucus cells of seromucous glands.​​​

Differences mucosa by anatomical localization

1- Nasal cavity

• Paired chambers seperated by bony and cartilagenous septum
• Divided into 3 regions
  
  • Nasal vestibule
    
    • Forms apart of the external nose and communicates with the external enviorment
    • Epithelium:
      
      • Stratified squamous epithelium
    • Contains a variable number of stiff hairs (vibrissae):
      
      • Entrap large particulate material.
    • Secretions of the sebaceous glands also assist in the entrapment of particulate matter.
  • Repiratory region:
    
    • ​The middle and lower conchae
    • Epithelium, lamina propria: typical
      
      • Warming of the air:
  • Olfactory region
    
    • Covers a specialized region of the mucosa of the superior conchae and the roof of the nasal cavities

Specilized Olfactory mucosa

• Epithelium: pseustratified, containing siffrent types of cells than respiratory mucosa
  
  • No goblet cells
  • 1- Olfactory (chemoreceptor) cells
    
    • Bipolar neurons, span the whole thickness of the epithlium
    • Modifications:
      
      • Dendrites are modified into receptor portion composed of the olfactory vesicle with long immotile cilia.
    • Pathway:
      
      • Receptor molecules for the odorants (smell-active chemical substances) are localized on the plasma membrane of these cilia and bind airborne odorants dissolved in the nasal secretion.
      • Axons of the olafactory cells (fila ofactoria) carry action potential (information) to the brain, non mylinated
    • Do not come together as a singal nerve, but are grouped into bundels that pass through the cribriform plate of the ethmoid bone
  • Supporting cells
    
    • Columnar, extend to the full thickness of the epithelium , most numerous
    • Have microvillous surface,
    • Contain lipofuscin (yellow-brownish pigment) and enzymes that take part in the inactivation of odorants.
  • Basal cells
    
    • Reserve cells; olfactory cells are replaced every 4 weeks.
    • Small, cuboidal
• ​Lamina P:
  
  • ​Continuous with periostium of bone
  • contains the branched tubuloacinar olfactory (Bowman’s) glands (4, 5).
    
    • Serous secretion
      
      • in contrast to the mixed mucous and serous secretions produced by glands in the rest of the nasal cavity.
    • Small nerves that are located in the lamina propria are the olfactory nerves: aggregated afferent axons that leave the olfactory cells and continue into the cranial cavity, where they synapse in the olfactory (cranial) nerves
  • Lipofuscin granules are prevalent in the gland cells,

2- Parasasal sinuses

• Lined with a thinner pseudostratified ciliated columnar epithelium
• Lamina propria contains only a few small glands and is continuous with periosteum.

3- Nasopharinx

• Lined with a pseudostratified ciliated columnar epithelium.
• The accumulation of the diffuse lymphatic tissue and lymphatic nodules in the posterior wall of the pharynx
  
  • Called the pharyngeal tonsil.
• In posterior to the openings of the auditory tubes occurs another accumulation of lymphatic tissue:
  
  • Tubal tonsils.

***Mucosa associated lymphoid tissue (MALT)

• TONSILS:
  
  • Aggregations of lymphatic tissue (diffuse and lymphatic nodules)
  • Clustered around the posterior opening of the oral and nasal cavities.
• Function: immunological protection at the entrance to the digestive and respiratory tracts
• This lymphatic tissue is organized into a Waldeyer ́s ring, tonsillar ring:
  
  • Palatine tonsils are located on either side of the entrance to the oropharynx between the palatopharyngeal and palatoglossal arches.
  • Tubal tonsils – in the lateral walls of the nasopharynx posterior to the opening of the Eustachian tube.
  • Pharyngeal tonsil – located in the posterior wall of the nasopharynx.
  • Lingual tonsil – is located at the root of tongue on its superior surface.

Definition:

Ciliated columnar epithelium (pseudostratified columnar epithelium with kinocilia) and numerous interspersed goblet cells

Structure

Basal : basal cells (stem cell reserves of goblet and ciliated cells)

Luminal : goblet cells (mucogenic), ciliated cells (bear kinocilia)

Properties:

Cleans the airways through mucus secretion and orally directed cilia motion (= mucociliary clearance)

Distribution: throughout the respiratory tract:

nasal cavity, nasopharynx, larynx, trachea, main bronchi to the terminal bronchioli

Question 2

Structure and function of the larynx and trachea

Answer 2

1- Larynx

General

• The larynx is a cartilaginous tube that connects the pharynx and the trachea.
• It is involved in producing sound, swallowing, breathing, and the cough reflex.
• It is composed of several cartilages (e.g., cricoid, thyroid, arytenoid) connected by ligaments, muscles (intrinsic and extrinsic), and membranes.
• The intrinsic muscles produce the fine movements necessary for sound production and breathing.
• The laryngeal cavity is divided into three parts:
  
  • the supraglottis (contains the false vocal cords),
  • glottis (contains the true vocal cord),
  • and subglottis.

Structure:

• Tunica mucosa:
  
  • Epithelium
    
    • The mucosa of the larynx forms two pairs of folds:
      
      • Upper are the vestibular folds (false vocal cords)
      • Lower are the vocal cords.
    • Laryngeal ventricle with ventricular recess:
      
      • Narrow pouchlike prolongation between these two pairs of folds
    • Vocal cord: covered by nonkeratinized stratified squamous epithelium:
    • Rest: lined by ciliated pseudostratified columnar epithelium with goblet cells.
• Lamina propria
  
  • Loose connective tissue containing blood vessels and diffuse lymphatic tissue.
  • Seromucous glands and lymphatic nodules (sometimes called the “laryngeal tonsils”)
    
    • Numerous in ventricular fold
    • Absebt, less where the vocal cords are present.
• Vocal cord
  
  • Apex of the true vocal fold is the vocalis ligament: with dense elastic fibers that extend into the adjacent lamina propria
  • Skeletal vocalis muscle.
    
    • The skeletal thyroarytenoid muscle and the thyroid cartilage constitute the remaining wall.**​
  • ​Control the flow of air though larynx and viabrate to produce sound
  • Define the lateral boundries of the opening to the larynx: rima glottidis
• The hyaline cricoid cartilage is the lowermost cartilage of the larynx.

2- Epiglottis

• Epiglottis: petal-shaped, attached to the inside of the thyroid cartilage on the posterior wall
• Projects from the upper rim of the larynx, elastic cartilage forms its skeleton
• Function:
  
  • Covers larynx during swalloing
• Structure:
• Ep:
• Lingual surface: stratified SQ non K
• Laryngeal surface: pseudostratifiled cilliated columnar
• Lamina P: loose ct, mixed seromucous glands that open twards larynx
• Elastic cartilage with perichondrium
• A central elastic cartilage of epiglottis forms the framework of the epiglottis.
• Lingual mucosa (anterior side)
  
  • is lined with a stratified squamous nonkeratinized epithelium (1).
  • Lamina propria:
    
    • merges with the connective tissue perichondrium of the elastic cartilage of epiglottis
• Laryngeal mucosa (posterior side).
  
  • Stratified squamous nonkeratinized covers the apex of the epiglottis and about half of the laryngeal mucosa (posterior side).
  • Toward the base the lining changes to pseudostratified ciliated columnar epithelium
  • Lamina propria
    
    • Tubuloacinar seromucous glands
• Taste buds and solitary lymphatic nodules may be observed in the lingual epithelium or laryngeal epithelium.​

3-Trachea

General:

• The trachea is a rigid, but flexible,
• It is continuous above with the larynx and below with two primary bronchi.
• Function: conduct of air to lungs
  
  • Lumen of trachea stays open because of arrangment of cartilagounous rings

Structure::

• The wall of the trachea consists of mucosa, submucosa, hyaline cartilage, and adventitia.
• The trachea is kept patent (open) by C-shaped hyaline cartilage (3) rings. Hyaline cartilage (3) is surrounded
• by the dense connective tissue perichondrium (9), which merges with the submucosa
• (4) on one side and the adventitia (1) on the other. Numerous nerves (6), blood vessels (8), and
• adipose tissue (2) are located in the adventitia.
• The gap between the posterior ends of the hyaline cartilage (3) is filled by the smooth trachealis
• muscle (7). The trachealis muscle (7) lies in the connective tissue deep to the elastic
• membrane (14) of the mucosa.Most of the trachealis muscle (7) fibers insert into the perichondrium
• (9) that covers the hyaline cartilage (3).
• Tunica mucosa:
  
  • Pseudostratified ciliated columnar epithelium with goblet cells.
    
    • RESPIRATPRY EPITHELIUM
  • Lamina propria:
    
    • Connective tissue fibers, diffuse lymphatic tissue, and occasional solitary lymphatic nodules.
    • Rich in cells:
      
      • lymphocytes, , plasma cells, mast cells, fibroblasts…
    • Located deeper in the lamina propria: longitudinal elastic membrane formed by elastic fibers.
• Submucosa
  
  • Loose connective tissue that is similar to that of lamina propria
  • Tubuloacinar seromucous tracheal glands
    
    • mucous secreting acini and serous demilunes, ducts are simple suboidal epithelium
    • Excretory ducts pass through the lamina propria to the tracheal lumen.
    • Especially in dorsal wall whew cartilage is absent
• Skeleton of the trachea forms 15 – 20 C-shaped hyaline cartilages
• A layer of smooth muscle cells (tracheal muscle) is stretched between the tips of cartilaginous rings.
• Adventitia is composed of the connective tissue that binds the trachea to adjacent structures. Arrangement of the tracheal wall provides its flexibility and also maintains patency of the lumen.
• Arrangement of the tracheal wall provides its flexibility and also maintains patency of the lumen.

Question 3

Structure and function of the lung

Answer 3

Respiratory Portion of the Respiratory System

• Distal continuation of the conducting portion
  
  • Starts with the air passageways where respiration or gaseous exchange occurs.
  • Conducting portion:
    
    • Bronchi, bronchioles, terminal bronchioles
    • Trachea divides into 2 branchs forming the main/primary bronchi→
    • Apon entering hilum of lung→ divides into lobar bronchi/secondary
    • Innitially the bronchi have the sam general histological arrangment as the trachea, but as they enter the lung the structure changes

Bronchial tree

• The wall of the large and medium sized bronchi
  
  • Mucosa
    
    • Pseudostratified ciliated columnar epithelium with goblet cells.
    • Lamina propria
      
      • Composed of the loose CT rich in lymphocytes and elastic fibers.
      • Smooth muscles form a layer of the criss-crossing bundles spirally arranged.
  • Submucosa
    
    • Seromucous glands
      
      • loose CT with smooth muscle fibers and fibroblasts
  • Outer layer of the wall
    
    • Formed by overlapping plates of the hyaline cartilage and adventitia.
    • Type II collagen
    • Bronchi are surrounded by lung parenchyma.
• As the bronchial diameter decreases:
  
  • Cartilage plates are smaller
  • Glands become less numerous
  • Pseudostratified columnar epithelium is lower and the number of goblet cells is reduced
• *Orcein:
  
  • visulaization of elastic fibers
    
    • elastic fibers in the alveolar wall
    • elastic fibers in the lamina propria
    • artery: internal elastic membrane
• *Immunoperoxidase
  
  • method for bombesin detecting neuroendocrine cells in the epithelium

Terminal brinchiole

• Mucosa
  
  • Lined with a simple columnar epithelium
    
    • Cells:
    • (no goblet cells)
    • Ciliated cells
    • Secretory Clara/club cells
      
      • Non cilliated cells
      • Apical part contains secretory granules.
      • Screte a surface-active agent, a lipoprotein that prevents luminal adhesion during expiration (bronchiolar surfactant).
      • Secretory protein (CC16), that has anti-inflammatory and immunomodulatory functions.
  • Lamina propria
    
    • Thin
    • Rich in elastic fibers.
  • Muscle layer contains smooth muscle cells spirally oriented.
  • NO CARTILAGE
  • Thin adventitia.
• TB branches into respiratory bronchioles.​
• • Respiration can only occur in alveoli because the barrier between inspired air in the alveoli and venous blood in capillaries is extremely thin.
• Other intrapulmonary structures in which respiration occurs are the alveolar ducts and alveolar sacs.
• In addition to the cells in the passageways, there are other cell types in the lung. The alveoli
• contain two cell types. The most abundant cells are the squamous alveolar cells or type I pneumocytes.
• These are extremely squamous cells that line all alveolar surfaces. Interspersed among
• the squamous alveolar cells either singly or in small groups are the type II pneumocytes. Lung
• macrophages, derived from circulating blood monocytes, are also found both in the connective
• tissue of alveolar walls or interalveolar septa (alveolar macrophages) and in the alveoli (dust
• cells). Also present in the interalveolar septa are extensive capillary networks, pulmonary arteries,
• pulmonary veins, lymphatic ducts, and nerves (Overview Figure 15).

Respiratory portion of the lung

• Respiratory portion of the lung is composed of
  
  • Respiratory bronchioles (RB)
  • Alveolar ducts (AD)
  • Alveolar sacs (AS)
  • Alveoli (A)

Respiratory bronchiole

• Serve as transition between conducting and respiratory portions.
• Usually accompanied by an artery
• Wall is interrupted by the openings to alveoli, where gas exchange occurs.
• Lined with a simple cuboidal epithelium, similar to TB
  
  • Composed of the ciliated and Clara cells,
• Underlying CT contains elastic fibers and circularly arranged smooth muscle cells.

Alveolar duct

• Are branches of RB.
• Have an incomplete wall: tube completely lined by openings of alveoli.
  
  • Openings of alveoli encircled by smooth muscles and covered with a cuboidal epithelium are visible as knoblike enlargments of interalveolar septa
• Alveolar ducts open into atria of two or more alveolar sacs.

Alveoli

• Thin-walled saclike evaginations with wide opening into RB, AD and AS.
• Structure:
  
  • Composed of thin layer of CT containing a very dense capillary network, cells (fibroblasts, macrophages) and ECM.
  • They are responsible for spongy structure of the lungs.
  • Air in the alveoli is separated from capillary blood
    
    • air-blood barrier.
• Function:
  
  • During inspiration the elastic fibers enable the alveoli to expand and the reticular fibers prevent overdistension of the alveoli and damage of capillaries.
• Interalveolar septum:
  
  • Fused walls of two neighboring alveoli
    
    • Reticular fibers – black
    • Elastic fibers – grey
    • Alveolar macrophage
      
      • derived from circulating blood monocytes
      • Location:
        
        • In the alveoli and in the interalveolar septum.
      • Function:
        
        • Phagocytose air-borne particles (dust, carbon, and bacteria) entering into the alveoli.
        • Move up by the mucociliary escalator for removal in the pharynx or stay in the interstitial tissue causing coloration of the lung
• Alveolar pores
  
  • (10-15 μm in diameter)
  • occurring between the alveoli
  • equalize air pressure in the alveoli and promote collateral circulation of air when a bronchiole is obstructed.

Alveolar lining, respiratory epithelium is composed of two cell types:

• Pneumocytes type I:
  
  • Extremely squamous cells that line all alveolar surfaces
  • Connected to each other by tight junctions
  • are the main sites for gaseous exchange.
  • Form the blood-air barrier, together with the endothelial cells of the capillaries and the basement membrane between the two cells.
• Pneumocytes type II​
  
  • Septal cells
  • Fewer in number and cuboidal in shape.
  • Contain dense-staining lamellar bodies in their apical cytoplasm.
    
    • phospholipids, GAG, and proteins.
  • Protruding apical surface is furnished with the short microvilli.
  • Synthesize and secrete a phospholipid-rich product called pulmonary surfactant.
    
    • Released into the alveolus
    • Surfactant spreads as a thin layer over the surfaces of type I alveolar cells, lowering the alveolar surface tension.
    • The reduced surface tension in the alveoli decreases the force that is needed to inflate alveoli during inspiration.
      
      • Stabilizes the alveolar diameters
      • Facilitates their expansion
      • Prevents their collapse during respiration
        
        • by minimizing the collapsing forces
  • Can divide and function as stem cells for type I squamous alveolar cell

​

AIR-BLOOD BARRIER

• Air in the alveoli is separated from capillary blood by three components:
  
  • Attenuated cytoplasmic part of the membranous pneumocyte (type I cell)
  • Fused basal laminae of the endothelial cell and pneumocyte
  • Cytoplasm of the endothelial cell
• Total thickness of this barrier varies from 0.1 to 1.5 μm.
• Endothelial cells of these continuous capillaries are extremely thin, contain many pinocytotic vesicles, and are joined by occluding junctions

FORMATION AND COMPOSITION OF SURFACTANT

• Surfactant produced by the secretory pneumocytes decreases the surface tension at the air-epithelium interface and actively participates in the clearance of foreign materials.
• Pulmonary surfactant is a mixture of phospholipids and surfactant proteins.
  
  • The most critical agent for air space stability is dipalmitoyl- fosfatidylcholin (DPPC).
  • Surfactant proteins help organize the surfactant layer and modulate alveolar immune responses.
• Without adequate secretion of surfactant, the alveoli would collapse on each successive exhalation.
  
  • Such collapse occurs in premature infants;
  • inadequate production of surfactant is the cause of the neonatal respiratory distress syndrome (RDS).
  • RSD not threatens the infant with immediate asphyxia (oxygen deficiency), but increased rate of breathing and mechanical ventilation lead to the damage of delicate alveolar lining, followed by the exudation and hyaline membrane formation.
• Surfactant synthesis is modulated by cortisol, prolactin, insulin, and thyroxine.
• In the clinic: Profylactic administration of exogenous surfactant at birth to extremely premature infants as well as the administration of Dexamethasone (a synthetic corticoid) to mothers with threatened premature delivery decrease neonatal mortality.