Respiratory Histology Lecture Notes - July 2024

Faculty of medicine Department of histology and genetics Respiratory system histology July 2024 Prof. Dr. Samia Tayeb Hawisa MB. Bch, PGCAP, MSc, PhD  ‫معا لحماية الحياة البرية في ليبيا‬...

Faculty of medicine Department of histology and genetics Respiratory system histology July 2024 Prof. Dr. Samia Tayeb Hawisa MB. Bch, PGCAP, MSc, PhD  ‫معا لحماية الحياة البرية في ليبيا‬ ‫ حيوان الكوكا أو المبتسم‪:‬‬ ‫ المبتسم دائما ً "والمهدد باالنقراض ألنه ودود جدا ً ‪..‬ويقترب من الثعالب والثعابين ليلعب معهم فيأكلوه‬  Respiratory System Lecture objectives: This lecture will discuss: The histologic characteristics of the components of conducting portion and respiratory portion of the respiratory system How these characteristics allow each component to contribute to the overall function of the respiratory system  Anatomy of the respiratory system Anatomically, the respiratory tract has 2 parts: Upper respiratory tract Lower respiratory tract  The upper air way Structure of the upper airway: Nose Pharynx Larynx and associated structures Functions of the upper airway: Passageway for gas flow Filter Heater Humidification Sense of smell and taste Phonation Protection of lower airways  Lower Airway It extend from the larynx down to the airways participating in gas exchange and consists of: trachea, bronchi, lungs Each branching of an airway produces subsequent generations of smaller airways. The first 15 generations are known as conducting airways because they convey gas from the upper airway to the structures that participate in gas exchange with blood. The microscopic airways beyond the conducting airways that carry out gas exchange with blood are classified as the respiratory airways. Histologically and functionally, the respiratory system has 2 portions: ⁎ The conducting portion: Is made up of the nose, pharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles, these components condition air and bring it into the lungs ⁎ The respiratory portion: where gas exchange actually occurs, consisting of respiratory bronchioles, alveolar ducts, and alveoli in the lungs.  Conducting portion  The conducting portion serves the following functions: - Conducting air: provide a channel or tube through which air moves to and from the lungs - Conditioning the inspired air - Moistening air  A combination of cartilage, elastic and collagen fibers, and smooth muscle provides the conducting portion with rigid structural support and the necessary flexibility and extensibility.  Function of the respiratory system Conduction - Maintenance of an open lumen - Ability to accommodate expansion and contraction - Warming, moisturizing and filtering of the inspired air Respiration - Rapid exchange of atmospheric gases - Alveolar wall cells secrete surfactant Ventilation The respiratory system aids in breathing, also called pulmonary ventilation. - The air is Inhaled through the nasal and oral cavities (the nose and mouth). It moves through the pharynx, larynx, and trachea into the lungs. - Then air is exhaled, flowing back through the same pathway.  Gas exchange in the respiratory system All higher animals require a mechanism to: - Obtain O2 from the environment - Get rid of CO2 This “gas exchange” is the function of the respiratory system Oxygen diffuses out and carbon dioxide diffuses into the air space of the alveolus  Respiratory epithelium The majority of the respiratory tree, from the nasal cavity to the bronchi, is lined by pseudostratified columnar ciliated epithelium. Most of the conducting portion is lined with ciliated pseudostratified columnar epithelium. As the degree of branching within the airway tree continues, the epithelium gradually changes from pseudostratified to simple cuboidal; and the predominant cells become non- ciliated cells, Clara cells. The bronchioles are lined by simple columnar to the cuboidal epithelium. The alveoli possess a lining of thin squamous epithelium that allows for gas exchange As the conducting airway transitions to terminal and transitional bronchioles, the histological appearance of the conducting tubes change. Secretory glands are absent from the epithelium of the bronchioles and terminal bronchioles, smooth muscle plays a more prominent role and cartilage is largely absent from the underlying tissue. Cellular transition from conducting airway to the alveolus  This epithelium has different cell types: ⁎ Ciliated columnar cells: are the most abundant, each with about 300 cilia on its apical surface. found in the nasal cavity and all the airways from the larynx to the terminal bronchioles. Ciliary beating can be effectively slowed or stopped if the viscosity of the mucous is increased by exposure to dry gas. It is also slowed or stopped after exposure to smoke, high concentrations of inhaled O2, and drugs such as atropine. ⁎ Brush cells: columnar cells, has small apical surface bearing a tuft of many short, blunt microvilli. Brush cells express some signal transduction components like those of gustatory cells and have afferent nerve endings on their basal surfaces and are considered to be chemosensory receptors. ⁎ Goblet cells: are abundant in some areas of the respiratory epithelium, filled in their apical portions with granules of mucin glycoproteins. Produce the thick layer of mucus that lines all but the smallest conducting airways. ⁎ Small granule cells: are also difficult to distinguish in routine preparations, but possess numerous dense core granules 100–300 nm in diameter. Like brush cells, they represent about 3% of the total cells and are part of the diffuse neuroendocrine system. ⁎ Basal cells: small rounded cells on the basement membrane and not extending to the luminal surface, are stem cells that give rise to the other cell types. ⁎ Clara cells: are non-ciliated, cuboidal, secretory epithelial cells in the small airways and trachea. They are also known as club cells (CCs) or bronchiolar exocrine cells. Clara cells have several lung protective functions, they secrete important defense markers and serve as progenitor cells after injury, make up a large portion of the epithelial lining in the latter portions of the conducting airway Epithelium in the respiratory system Air-conducting tubes of the respiratory system  Respiratory Portion (Site of Gases Exchange) At the end of each bronchiole is a cluster of little air sacs called alveoli. Alveoli are wrapped in tiny blood vessels called capillaries. The breathed air fills these air sacs with oxygen-rich air. This is where the exchange of gases occurs. Respiratory portion consists of: ⁎ Respiratory bronchioles ⁎ Alveolar ducts ⁎ Alveolar sacs ⁎ Alveoli The four steps of gas exchange are: ⁎ Ventilation ⁎ Pulmonary gas exchange ⁎ Gas transport ⁎ Peripheral gas exchange.  Surfactant Surfactant is an agent that decreases the surface tension between two media. The surface tension between gaseous-aqueous interphase in the lungs is decreased by the presence of a thin layer of fluid known as pulmonary surfactant. The pulmonary surfactant is produced by the alveolar type-II (AT-II) cells of the lungs. Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant contains neutral lipids, phospholipid (dipalmitoylphosphatidylcholine), and four surfactant-associated proteins, SP-A, SP-B, SP- C, and SP-D.  Function of mucus in the respiratory system Mucus has an important role in lung's immune response because it traps irritants in airways and helps allow the body to expel them through coughing. It is essential for the transport of dust, debris, irritants and bacteria from the lungs. Traps dust and washes it away Detoxifies gases Mucus has a role in diluting irritants which enter the airway and so it renders them less harmful. There is growing evidence that mucus has antibacterial and antiviral properties. This helps treat and protect from infection. Contains IgA antibodies to guard against infection Has protein that presents odor chemicals to receptors of olfactory cells Washes away current chemicals to allow one to smell the next chemical odor  Nose What does your nose do for you? Beyond its important role as the collector of olfactory information–such as smoke that warn of impending danger or smells that whet the appetite –the nose acts as an air conditioner for the respiratory system. Everyday, it treats approximately 500 cubic feet of air, the amount enclosed in a small room.It filters dust, traps bacteria from the air, brings air to the temperature of the body and also adds moisture. The nose has some lesser-known functions. Among them it gives your voice resonance, adding a richness of tone that would otherwise be lacking. Smell (Olfaction): The sense of smell, or olfaction, is the special sense through which smells (or odors) are perceived.  Nasal cavity The left and right nasal cavity each has two components: - The external vestibule - The internal nasal cavities (or fossae). The vestibule is the most anterior and dilated portion of each nasal cavity. Skin of the nose enters the nares (nostrils) partway up the vestibule and has sweat glands, sebaceous glands, and short coarse vibrissae (hairs) that filter out particulate material from the inspired air. Within the vestibule, the epithelium loses its keratinized nature and undergoes a transition into typical respiratory epithelium before entering the nasal fossae. The nasal cavities lie within the skull as two cavernous chambers separated by the osseous nasal septum. Extending from each lateral wall are three bony shelf-like projections called conchae. The middle and inferior conchae are covered with respiratory epithelium; the superior conchae are covered with a specialized olfactory epithelium.  Olfactory epithelium Olfactory epithelium, a specialized region of the mucous membrane covering the superior conchae at the roof of the nasal cavity. In humans, it is about 10 cm2 in area and up to 100 mm in thickness. It is a pseudostratified columnar epithelium composed of three types of cells: ⁎ Basal cells are small, spherical or cone-shaped and form a layer at the basal lamina. They are the stem cells for the other two types. ⁎ Supporting cells are columnar, with broad, cylindrical apexes and narrower bases. On their free surface are microvilli submerged in a fluid layer. Well-developed junctional complexes bind the supporting cells to the adjacent olfactory cells. ⁎ Olfactory neurons are bipolar neurons present throughout this epithelium. They are distinguished from supporting cells by the position of their nuclei, which lie between those of the supporting cells and the basal cells. The dendrite end of each olfactory neuron is the apical (luminal) pole of the cell and has a knoblike swelling with about a dozen basal bodies. The (basal) axons of these neurons, which leave the epithelium and unite in the lamina propria as very small nerves which then pass through foramina in the cribriform plate of the ethmoid bone to the brain. There they form cranial nerve I, the olfactory nerve, and eventually synapse with other neurons in the olfactory bulb. The lamina propria of the olfactory epithelium possesses large serous glands (glands of Bowman), which produce a flow of fluid surrounding the olfactory cilia and facilitating the access of new odoriferous substances. Olfactory epithelium  Sinuses & nasopharynx The nasal cavity is above the roof of the mouth (called the palate) and surrounded by the paranasal sinuses. It joins with the nasopharynx, which is the upper part of the throat (pharynx) at the back of the mouth. The paranasal sinuses are bilateral cavities in the frontal, maxillary, ethmoid, and sphenoid bones of the skull. They are lined with a thinner respiratory epithelium with fewer goblet cells. The lamina propria contains only a few small glands and is continuous with the underlying periosteum. The paranasal sinuses communicate with the nasal cavities through small openings and mucus produced in the sinuses is moved into the nasal passages by the activity of the ciliated epithelial cells.  The larynx The larynx is located in the anterior part of the throat and extends from the base of the tongue to the trachea. It plays an essential role in all upper airway functions, including respiration, phonation, cough reflex, swallowing, and vomiting. The larynx is connected by membranes and muscles superiorly to the hyoid bone and consist of nine cartilages connected to one another by muscles and ligaments. The first three of the cartilages which are the thyroid, cricoid and epiglottis are unpaired while the rest are paired. The epiglottis is the most superior cartilage. The superior opening of the larynx is the glottis and it is guarded by the epiglottis to help keep materials out from the respiratory tract during swallowing. The glottis is also closed to help in holding the breath against pressure in the thoracic cavity, when straining to lift a heavy weight or to defecate. The epiglottis is made up of elastic cartilage and is attached to the thyroid cartilage and projects superiorly towards the tongue. Larynx  Functions of the larynx Function of the larynx include: The thyroid and cricoid cartilages maintains an open passageway for air movement. The larynx prevents the entry of swallowed materials into the lower respiratory tracts and regulates the passage of air into and out of the lower respiratory tract. The vocal cords are the primary source of sound production. The pseudo stratified ciliated columnar epithelium lining the larynx produces mucus which traps debris in the air and the cilia moves the mucus and the debris into the pharynx where it is swallowed  Lining of the larynx The lumen of the larynx is lined mainly with respiratory epithelium, consisting of: Ciliated pseudostratified columnar epithelium with a rich population of goblet cells a submucosa containing mixed mucous and serous glands.  Trachea The trachea is 12-14 cm long and lined with a typical respiratory mucosa. In the lamina propria numerous sero-mucous glands produce watery mucus and in the submucosa 16–20 C-shaped rings of hyaline cartilage keep the tracheal lumen open. The open ends of the cartilage rings are on the posterior surface, against the esophagus, and are bridged by a bundle of smooth muscle (trachealis muscle) and a sheet of fibroelastic tissue attached to the perichondrium. The entire organ is surrounded by adventitia. The trachealis relaxes during swallowing to facilitate the passage of food by allowing the esophagus to bulge into the lumen of the trachea, with the elastic layer preventing excessive distention of the lumen. In the cough reflex the muscle contracts to narrow the tracheal lumen and provide for increased velocity of the expelled air and better loosening of material in the air passage. The bronchus in the lungs are lined with hair-like projections called cilia that move microbes and debris up and out of the airways.  Goblet cells are situated in the epithelium of the conducting airways, often with their apical surfaces protruding into the lumen, a location which fits them for a rapid response to inhaled airway insults. Scattered throughout the cilia and secrete mucus which helps protect the lining of the bronchus and trap microorganisms.  Brush cells, also termed tuft, caveolated, multivesicular, and fibrillovesicular cells, are part of the epithelial layer in the gastrointestinal and respiratory tracts. The cells are characterized by the presence of a tuft of blunt, squat microvilli (∼ 120–140/cell) on the cell surface.  Basal cells provide an attachment site for ciliated and goblet cells to the basal lamina. They also respond to injury and act in oxidant defense of the airway epithelium and transepithelial water movement. Within the hundreds of millions of microscopic alveolar sacs, the exchange of oxygen for carbon dioxide occurs.  The supporting lamina propria underneath the epithelium contains elastin, that plays a role in the elastic recoil of the trachea during inspiration and expiration, together with blood vessels that warm the air. The sub-mucosa contains glands which are mixed sero- mucous glands.  The adventitia is a loose connective tissue layer covers the external tracheal surface.  The bronchial tree and lungs The trachea divides into two primary bronchi that enter the lungs at the hilum, along with arteries, veins, and lymphatic vessels. After entering the lungs, the primary bronchi course downward and outward, giving rise to three secondary (lobar) bronchi in the right lung and two in the left lung, each of which supplies a pulmonary lobe. These lobar bronchi again divide, forming tertiary (segmental) bronchi. Each of these tertiary bronchi, together with the smaller branches it supplies, constitutes a bronchopulmonary segment—approximately 10–12% of each lung with its own connective tissue capsule and blood supply. The tertiary bronchi give rise to smaller and smaller bronchi, whose terminal branches are called bronchioles. Each bronchiole enters a pulmonary lobule, where it branches to from five to seven terminal bronchioles. The pulmonary lobules are pyramid-shaped, with the apex directed toward the pulmonary hilum. Each lobule is delineated by a thin connective tissue septum, best seen in the fetus. In adults these septa are frequently incomplete, resulting in a poor delineation of the lobules. Moving through the smaller bronchi and bronchioles toward the respiratory portion, the histologic organization of both the epithelium and the underlying lamina propria gradually becomes more simplified.  Bronchus  Pseudostratified ciliated columnar epithelium with goblet-cells  Smooth muscle band between the lamina propria and the cartilage  The smooth muscle is not continuous around the bronchus as it spirals  A change from cartilage rings to cartilage plates surrounding the tube  Glands in the submucosa  Bronchioles Bronchioles: Folded respiratory epithelium Have a ciliated columnar epithelium The bronchioles are lined by simple columnar to the cuboidal epithelium The epithelial cells mainly lining the bronchial tree are ciliated columnar cells that are tightly packed and coupled by gap junctions. They do not have cartilage plates or glands Have well organized, prominent circular layer muscle layers After the tertiary segmental bronchi, the airways continue to fan out into bronchioles. Bronchioles then divide into three types: conducting, terminal, and respiratory. Natural defenses of respiratory system Bronchial asthma  Pulmonary changes in pneumonia and emphysema In pneumonia: The infection causes the lungs' air sacs (alveoli) to become inflamed and fill up with fluid or pus and cells. That can make it hard for the oxygen to get into the bloodstream. In emphysema: The walls between many of the air sacs in the lungs are damaged. This causes the air sacs to lose their shape and become floppy. The damage can destroy the walls of the air sacs, leading to fewer and larger air sacs instead of many tiny ones. Abnormal permanent enlargement of lung air spaces with the destruction of their walls without any fibrosis and destruction of lung parenchyma with loss of elasticity. Emphysema Emphysema-destruction of alveolar wall Means too much air in the lungs.  Effects of cigarette smoking on the respiratory epithelium Cigarette smoking exposes epithelial cells to harmful chemicals and carcinogens. These harmful agents can damage airway epithelial cells, causing inflammation and increasing the risk of lung cancer Heavy smoking destroys pseudostratified ciliated epithelium in the trachea Damaged epithelial cells stimulate the release of more pro-inflammatory chemokines/cytokines, exacerbating epithelial cell damage Cigarette smoke induced tracheal changes including shortening of cilia and loss of ciliated cells. Most smokers have undergone tracheal metaplasia. This means that the normal pseudostratified ciliated columnar epithelium of the airways is converted to another type, usually stratified squamous. The effects of tobacco smoke on the respiratory system include: irritation of the trachea and larynx reduced lung function and breathlessness due to swelling and narrowing of the lung airways and excess mucus in the lung passages.  Smoking - Smoking can cause lung disease by damaging airways and alveoli. - Lung diseases caused by smoking include COPD (emphysema and chronic bronchitis) and lung tumors  Deficiency of lung surfactant Deficiency of lung surfactant in premature newborns causes respiratory distress syndrome (RDS), a leading cause of perinatal mortality. Supplementing exogenous surfactants extracted from animals' lung to preemies suffering from RDS has completely altered neonatal care in industrialized countries. Surfactant therapy has also been applied to the acute respiratory distress syndrome (ARDS) but to date with only limited success, which might be in part due to surfactant inhibition.  ARDS in COVID-19 The notable mechanisms of COVID-19-associated ARDS include severe pulmonary infiltration/edema and inflammation, leading to impaired alveolar homeostasis, alteration of pulmonary physiology resulting in pulmonary fibrosis, endothelial inflammation and vascular thrombosis. Phospholipids found in surfactants play a part in preventing virally induced inflammation and infection. Moreover, the protein component has antiviral properties. Type II alveolar cells infected by SARS-CoV-2 could not properly secrete the endogenous surfactant According to studies, lung surfactant inhalation was linked to a reduction in respiratory illnesses. The COVID-19 patients with ARDS who received surfactant therapy had lower hospitalization stays and mortality rates, indicating that surfactant therapy may improve clinical outcomes in COVID-19 patients with ARDS.