The Conducting DivisionThis division includes structures fromnasal cavity to terminal bronchioles.
The Nasal Cavity• The nasal cavity lies between the ethmoid bone superiorly and the palate inferiorly, and is vertically divided into two halves by the nasal septum. It functions to condition the air that passes into the lungs, houses the olfactory epithelium, and acts as a resonant chamber to enhance speech.• Most of the chamber is lined with a pseudostratified, ciliated epithelium with goblet cells, called "respiratory epithelium" because it lines the conducting division of the respiratory system. Note that "respiratory epithelium" does not actually carry out gas exchange.• In this horizontal section through the nasal cavity, identify the cartilaginous nasal septum and the turbinate bones (conchae) (1X). Examine the lining epithelium, identifying ciliated columnar cells and goblet cells (40X). Note that the goblet cells are thinner, and therefore somewhat harder to identify, than the ones in the digestive system.• In the adult, the lamina propria normally contains large numbers of blood vessels and seromucous glands; very few of these are present in this fetal specimen (1X, 10X).• What is the function of the goblet cells and seromucous glands of the nasal cavity? – Mucus secreted by them is helpful in trapping smaller foreign particles
Olfactory Epithelium• The roof of the nasal cavity and the superior turbinate bone (concha) are covered with an epithelium specialized for olfaction. Olfactory epithelium is categorized as pseudostratified columnar epithelium, without goblet cells (4X, 20X).• Within the underlying lamina propria, identify venules, as well as the nerve fibers arising from the olfactory cells in the epithelium (40X). These nerve fibers (fila olfactoria) conduct olfactory information to the brain through holes (the cribriform plate) in the intervening (ethmoid) bone.• Also identify the serous Bowmans glands (20X, 40X), and their ducts that penetrate to the surface of the epithelium. These glands are unique to the olfactory epithelium. The fluid released by the Bowmans glands serves to trap odor molecules, which are then detected by the membrane-bound odorant receptors of the olfactory cells.
The Pharynx: Oropharynx & Laryngopharynx• Note that these structures differ from nasopharynx with respect to type of mucosa, in that they contain non-keratinized stratified squamous epithelium (10X, 40X). Why? – The stratified squamous epithelium protects against abrasive activities, like swallowing or coughing• Identify the lamina propria, and note that it contains abundant elastic fibers, lymphatic tissue, and mucous and serous glands (5X). Lamina propria
The Pharynx: Nasopharynx• No slide available• Here, the epithelium is pseudostratified ciliated. Why not stratified squamous? – Nasopharynx is used exclusively for breathing, so it is lined with the usual respiratory (pseudostratified ciliated) epithelium
The Soft Palate• This structure (0.3X) separates oropharynx and nasopharynx (note that the orientation of slide E-43A in the Virtual Microscope puts the oral cavity facing up).• Note that the epithelium on the nasal surface (1X, 3X, 10X) is pseudostratified ciliated, while the epithelium on the oral surface (10X) is stratified squamous. Why? – The nasal surface is only exposed to air and therefore has respiratory epithelium – The oral surface, on the other hand, is exposed to food/swallowing and needs a tougher stratified squamous epithelium• What is the function of the skeletal muscle of the soft palate? Epithelium of nasal surface Epithelium of oral surface
The Larynx• The larynx connects pharynx with trachea, and contains the vocal cords
The Larynx: MucosaEpithelium.• Note that most of the larynx is covered at its luminal surface (40X) by pseudostratified ciliated columnar epithelium with goblet cells. In the region of the true vocal fold, however, the epithelium is stratified squamous (4X, 40X). Why? – Epithelium of true vocal cords protect the mucosa from frictional forces during phonationLamina propria.• Note that this layer is thick, and has abundant elastic Most of larynx Region of true vocal cord fibers (4X, 10X).• Identify tubuloacinar mucous, serous, and mixed seromucous glands (1X, 4X, 10X, 10X).• Identify lymph nodules (4X). Why would you expect them to be present here? – Protects against antigens and allergens arriving in the inhaled air
The Larynx: Submucosa, Vocal Cords, CartilageSubmucosa (No recognizable submucosa is present here.)Vocal folds.• Examine the region deep to (i.e. external to) the lamina propria of the vocal folds, and identify a large muscle mass (4X), comprised of skeletal muscle (20X, 20X). What is the function of this muscle?Cartilage.• Identify the mass of cartilage (1X) deep to the lamina propria within the epiglottis. Why is this type of cartilage located here?• Note that the oral surface of the epiglottis is covered with stratified squamous epithelium (20X), while the pharyngeal surface has a covering of pseudostratified columnar epithelium with goblet cells (20X). Why? – Oral surface is exposed to food/swallowing, while pharyngela surface is only exposed to air Oral surface of epiglottis Pharyngeal surface of epiglottis
The Larynx: Submucosa, Vocal Cords, Cartilage Cartilage. • Speculate on the reason for fat within the epiglottal cartilage (5X).Cartilage in epiglottis is dark region Fat in the epiglottal cartilage
Pseudostratified Ciliated Columnar Epithelium of Laryngeal Mucosa
Stratified Squamous Epithelium of Laryngeal Mucosa (vocal cords)
The Trachea: MucosaEpithelium.• Note the typical respiratory tract epithelium (10X; 10X); at this level in the respiratory tree, it is pseudostratified ciliated columnar epithelium with goblet cells (40X; 40X).• Examine the thick yellow line subjacent to the epithelium; this basal lamina (40X) is the thickest in the body.Lamina propria.• Note the abundance of lymphocytes (20X, 40X) and some solitary lymph nodules (4X).• Identify the longitudinal elastic membrane (20X, 40X) in deep lamina propria. This layer forms the boundary between the mucosa and submucosa.
The Trachea: Submucosa & AdventitiaSubmucosa.• Identify mixed tubuloalveolar glands (10X, 40X, 40X) in this region; try to follow a duct (10X) to the luminal surface.• Note the high vascularity of the submucosa (10X; 20X). What "conditioning" function does this vascularity provide? – High vascularity helps HEAT the inhaled airAdventitia.• Horseshoe-shaped, incomplete rings of tracheal cartilage (10X) lie external to the submucosa. Examine both longitudinal (4X) and cross sections (4X) of trachea to study these. Longitudinal Cross-section
The Trachea: Submucosa & Adventitia• Examine the area of posterior tracheal wall lacking cartilage (cross section); note that bundles of smooth muscle (trachealis muscle, 4X, 5X; 40X) connect the ends of the cartilage.• Examine the area between two adjacent cartilages (4X) (cross- section).
The LungsDIVISION REGION SUPPORT GLANDS EPITHELIUM CELL TYPES ADDITIONAL FEATURES sebaceous and sweat stratified squamous nasal vestibule hyaline cartilage epidermis vibrissae glands keratinized hyaline cartilage and basal, goblet, ciliated, nasal cavity: respiratory seromucous glands respiratory erectile-like tissue bone brush, serous, DNES Bowmans glands olfactory, sustentacular, nasal cavity: olfactory bone olfactory olfactory vesicle (serous) basalExtrapulmonary basal, goblet, ciliated, pharyngeal tonsils,conducting nasopharynx skeletal muscle seromucous glands respiratory brush, serous, DNES eustachian tubes respiratory and hyaline and elastic mucouse and basal, goblet, ciliated, epiglottis, vocal folds, larynx stratified squamous cartilages seromucous glands brush, serous, DNES vestibular folds nonkeratinized trachea and primary hyaline cartilage and mucous and basal, goblet, ciliated, C-rings and trachealis respiratory bronchi dense irregular C.T. seromucous glands brush, serous, DNES s.m. in adventitia plates of hyaline secondary hyaline cartilage and basal, goblet, ciliated, cartilage and two (intrapulmonary) seromucous glands respiratory smooth muscle brush, serous, DNES ribbons of helically bronchi oriented s.m. less than 1mm inIntrapulmonary simple columnar to ciliated cells and Clara diameter; supply air to primary bronchioles smooth muscle NO glandsconducting simple cuboidal cells lobules; two ribbons of helically oriented s.m. less than 0.5mm in some ciliated cells and diameter; supply air to terminal bronchioles smooth muscle NO glands simple cuboidal many Clara cells (no lung acini; some smooth goblet cells) muscle alveoli in their walls; ciliated cuboidal cells, some smooth muscle simple cuboidal and alveoli have smooth respiratory bronchioles No glands Clara cells, Types I and II and collagen fibers simple squamous muscle sphincters in pneumocytes their opening Type III collagen no walls of their own, Types I and II alveolar ducts (reticular) fibers; s.m. NO glands simple squamous only a linear sequenceRespiratory pneumocytes sphincters of alveoli of alveoli Type III collagen and Types I and II alveolar sacs NO glands simple squamous clusters of alveoli elastic fibers pneumocytes 200 microns in Type III collagen and Types I and II
Bronchi• Extrapulmonary (primary) bronchi. These branches of the conducting division resemble the trachea, but have a smaller diameter.• Intrapulmonary (secondary and tertiary) bronchi. These branches differ from extrapulmonary bronchi in several ways: – Examine several bronchi (small: 10X, 40X; medium: 4X, 40X, 100X; large: 4X, 40X), and note that mucosal epithelium decreases in height, and in frequency of goblet cells, as bronchi decrease in size. – Note that the epithelium (10X, 40X) of the smallest bronchi is ciliated simple columnar with goblet cells. – Note the presence of many reticular and elastic fibers (20X) in the lamina propria.
BronchiIntrapulmonary (secondary and tertiary) bronchi.• These branches differ from extrapulmonary bronchi in several ways:• Identify the muscularis mucosa (10X, 40X), a layer of interlacing smooth muscle bundles that spiral around the bronchus between mucosa and submucosa. Abundant elastic fibers intermingle with muscle bundles here.• Note that, as in trachea and extrapulmonary bronchi, the loose C.T. submucosa contains many mucous and mixed seromucous glands (10X, 40X).• Cartilage is present in bronchial adventitia as irregular plates rather than C-shaped rings (schematic). As a result, the cross-sectional appearance is round, not D-shaped as in trachea. Identify such plates (4X, 4X, 10X, 10X) , and note that smaller bronchi have progressively less cartilage.
Bronchioles: Mucosa• Tertiary bronchi branch into bronchioles (20X), which are conducting passageways embedded in little or no connective tissue, and surrounded by (but not in direct communication with) pulmonary alveoli.• Mucosal epithelium. This varies from ciliated simple columnar with a few goblet cells, to ciliated cuboidal (100X) with no goblet cells (in terminal bronchioles).• Identify non-ciliated Clara cells, also known as bronchiolar cells (schematic; 50X, 100X) scattered in the epithelium. The number of Clara cells increases as bronchiole diameter decreases, such that terminal bronchioles have more non-ciliated Clara cells than ciliated cuboidal respiratory epithelial cells.• Note that Clara cells (50X, 100X) bulge prominently into the lumen (airway).• Identify the muscularis mucosae (10X, 20X, 40X, 40X). of spirally arranged smooth muscle, which is prominent here
Bronchioles: Submucosa & Adventitia• Submucosa. Note that, in bronchioles (10X, 20X), this layer lacks seromucous and mucous glands.• Note that bronchioles (10X, 20X) have no cartilage.• Adventitia. Note that this layer is much less prominent (10X, 20X) than in larger branches of the conducting division.
The Respiratory Division The respiratory division comprises allrespiratory tree branches smaller than terminal bronchioles (respiratory bronchioles, alveolar ducts, alveoli). Gaseous exchange occursthrough alveoli located throughout this division.
Respiratory Bronchioles• Identify a terminal bronchiole that leads into a respiratory bronchiole (10X). What important functional characteristic distinguishes respiratory bronchioles from other types of bronchiole? – Respiratory bronchioles have alveoli, while terminal bronchioles do not. (Respiratory bronchioles are involved in gas exchange; terminal bronchioles are not.) – Alveolar ducts do not have epithelial walls of their own, so they are seen as openings in the epithelial lining at the transition from terminal bronchiole to respiratory bronchiole.• Note how the mucosa changes as the airway size decreases: large respiratory bronchioles have cuboidal epithelial cells with occasional cilia (100X), while the epithelium of smaller respiratory bronchioles (100X, 100X) has no cilia and is low cuboidal to squamous.
Respiratory Bronchioles• Note the absence of goblet cells. Why would mucus not be a good idea here? – A mucus lining in the respiratory bronchioles would interfere with gas exchange. The air should already be filtered of foreign particles by the time it arrives in the respiratory division.• Note the presence of a prominent smooth muscle muscularis mucosae (20X) with many elastic fibers (100X).
Alveolar Ducts• Note that these ducts have walls interrupted by numerous alveoli and alveolar clusters (20X).• Note the the muscularis mucosae here is reduced to drumstick-like knobs of smooth muscle (circled) at sites where duct wall interruptions occur (20X, 50X).• What type of epithelium is present here? – Type I and II pneumocytes – Type I: thin squamous cells that represent 95% of alveolar lining – Type II: secrete surfactant
Alveolar Sacs & Alveoli• Alveolar Septum: Gaseous exchange occurs here, between the lumen of the alveolus and pulmonary capillary blood. – Mucosa • The squamous epithelium in this region is greatly attenuated (thinned). • Identify Type I pulmonary epithelial pneumocytes (100X, 100X) with flattened nuclei, and cytoplasm so attenuated that it is not visible by light microscopy. The pulmonary epithelium and the vascular endothelium are too thin and close together to be distinguishable by light microscopy; the structure of the blood-air interface is clearly seen by electron microscopy (EM). • Identify Type II pneumocytes, also called Great cells (schematic; 100X, 100X, 100X) scattered among pulmonary epithelial cells and bulging into the alveolar lumen. What substance do these cells produce? – surfactant
Alveolar Sacs & Alveoli• Alveolar septum: – Pulmonary arteries • Identify pulmonary capillaries within the interalveolar septum (100X, 100X). • Identify the endothelial cells of these capillaries (100X, 100X, 100X, 100X); note that they have very attenuated (thinned) cytoplasm. Why? – A thin epithelium promotes more efficient gas exchange – Zona diffusa • The tissue space within the septum is comprised of reticular and elastic fibers and fine collagenous fibers; it lies between the basal laminae of the pulmonary epithelium and the endothelium. • Look for alveolar phagocytes (100X, macrophages) within the septa.
Clinical Correlation1. Tuberculosis (Pathology slide HD008). Tuberculosis is a chronic, infectious disease caused by the organism Mycobacterium tuberculosis; the disease causes 6% of all deaths worldwide. Within the lung, macrophages internalize invading mycobacteria; once inside the macrophage, however, the organism inhibits normal lysosomal function and continues to replicate. The body mounts a huge macrophage-based response that results in the formation of large tubercles (0.3X, 1X); these characteristic structures contain a central area of necrotic tissue sourrounded by large numbers of multinucleated giant cells and other cells of the immune system (40X).
Clinical Correlation2. Emphysema (Pathology slide HD068) Emphysema is a disease characterized by enlargement of airspaces distal to the terminal bronchioles, and destruction of their walls (septa). Alveolar walls become thin and eventually disappear. The fusion of adjacent alveoli results in large airspaces (overview, 5X); this reduces the amount of surface area available for gas exchange, causing shortness of breath. Emphysema and cigarette smoking are strongly associated, and the most severe form of the disease occurs in the heaviest smokers.
Clinical Correlation3. Hyaline Membrane Disease (Pathology slide HD069) Hyaline membrane disease often occurs in babies born before ca. 24 weeks gestation, which is the point at which Type II pneumocytes begin to produce surfactant. The detergent-like properties of surfactant reduce the surface tension of lung fluid, permitting expansion of the lungs. Without surfactant, too much force is required to open the alveolar spaces, which instead remain collapsed (overview, 10X).
Clinical Correlation4. Squamous cell carcinoma (Pathology slide HD073) Squamous cell carcinomas of the lung usually begin at the hilum of the bronchial tree. The bronchial epithelium, normally pseudostratified, becomes squamous and less organized (dysplasia). Eventually, uncontrolled growth results in large masses that push into the parenchyma of the lung (overview). In many cases, such tumors show whorls of well- differentiated squamous cells (10X). About 90% of lung cancers occur in smokers.