Copy of RESPIRATORY SYSTEM.docx

**RESPIRATORY SYSTEM** Functions of Respiratory System: 1. 2. 3. 4. 5. 6. 7. 8. The **primary functions of the respiratory system** are 1) **smell**, 2) **air conduction**, and 3) the **exchange of oxygen and carbon dioxide between the animal and the environment**, referred to as respira...

**RESPIRATORY SYSTEM** Functions of Respiratory System: 1. 2. 3. 4. 5. 6. 7. 8. The **primary functions of the respiratory system** are 1) **smell**, 2) **air conduction**, and 3) the **exchange of oxygen and carbon dioxide between the animal and the environment**, referred to as respiration. Respiration occurs at the air-blood interface, which lies at the **most distal part of the respiratory tract**. Although this exchange of oxygen and carbon dioxide is the ultimate functional goal of the respiratory tract, air must first be transported to this air-blood interface. Therefore, the **two crucial functions of the respiratory tract are air conduction and respiration**. FYI - clinical discussion of the respiratory tract is generally divided into the upper respiratory tract and lower respiratory tract. The upper respiratory tract consists of the nasal cavity and nasopharynx and larynx, whereas the lower respiratory tract includes the trachea, bronchi, bronchioles, and alveoli. Histologically the lower and upper respiratory tracts are very similar, whereas regions of conduction and gas exchange differ. Therefore, the structures of the respiratory system are grouped differently when dealing with the microanatomy of the respiratory tract. See below: **Functionally**, **structures of the respiratory system can be subdivided into three groups**: **CONDUCTIVE (1)** - conduction of air from the environment to inside the body Conducting system **brings air from the environment to** **respiratory portion**; it **cleanses, moistens and warms the** **incoming air** on its way. Hair and secretions from mucous glands in the nasal cavity **trap particulate matter**. **TRANSITIONAL (respiratory bronchioles) (2)** The transitional system is the **transition zone between the** **conducting (ciliated) and the gas exchange (alveolar system)** areas of the respiratory tree. The transitional system **consists** **exclusively of respiratory bronchioles** (bronchioles with outpocketings of gas exchange tissue (alveoli) lined by **Club cells, non-ciliated secretory cells, very few ciliated** **Cells and very few to no goblet cells**. **GAS EXCHANGE (alveoli) (3)** The exchange system is composed of alveoli; thin-walled structures **enveloped by** a rich network of capillaries: the **pulmonary capillaries**. **Alveoli are lined by epithelial type I** **(membranous) and type II pneumocytes**. NASAL CAVITY → NASOPHARYNX → LARYNX → TRACHEA → BRONCHI → BRONCHIOLES RESPIRATORY BRONCHIOLES → ALVEOLAR DUCTS → ALVEOLAR SACS → ALVEOLI (blue = conducting system; red = transitional system; green = gas exchange system) **NASAL CAVITY** The paired **external apertures of the nasal cavities** in domestic species are termed the **external nares (nostrils)**. During inspiration, air enters through the nares into the **most rostral segment of the nasal cavity**: the **nasal vestibule**. The **vestibule of most species** is **lined by keratinized stratified squamous epithelium** that may contain hair follicles. The stratified squamous epithelium of the vestibule **abruptly transitions into the characteristic respiratory epithelium**. Traditional respiratory epithelium is **ciliated, pseudostratified columnar epithelium.** traditional respiratory epithelium = ciliated, pseudostratified columnar epithelium Respiratory epithelium is primarily composed of these **ciliated columnar epithelial cells with basal nuclei** **and interspersed with moderate numbers of goblet cells** and **submucosal serous cells**. Goblet cells secrete mucus; characterized by cytoplasm filled with poorly staining, basophilic material (mucin) Movement of cilia removes mucus with trapped airborne inhaled particles such as dust and microorganisms.  Nasal cavity, horse; Respiratory epithelium is typified by a pseudostratified and ciliated columnar epithelium interspersed with mucin-filled secretory cells (goblet cells). Ciliated epithelial cells are connected by gap junctions and each ciliated epithelial cell has numerous (approximately 250) cilia on its surface; their tips have claws of dynein and beat in unison (but movement resembles a wave from cell to cell) to move mucus. Together, cilia and goblet cells constitute a cleaning apparatus of upper respiratory passages. Dysfunction caused by immotile cilia syndrome (aka Kartagener's syndrome). Respiratory epithelium lines the luminal surface of the nasal cavity, including the nasal turbinates. The **nasal turbinates** are **scroll-like structures within the nasal cavity** that are **formed by a thin core of bone**. The lamina propria and submucosa lie below the respiratory epithelium. The submucosa supports the lamina propria. The lamina propria may contain variable numbers of **tubuloalveolar secretory glands**. These glands **may be composed of serous cells, mucous cells, or a mixture** of serous and mucous cells. These **glands secrete into ducts that communicate with the surface epithelium**. Nasal cavity, mouse. The nasal cavity is a **bilaterally symmetric** structure with left and right sides **separated by a bony to cartilaginous nasal septum** (S). The nasal cavities are composed of **air filled openings, called meati (singular = meatus**; **M**) **filled with scroll-like structures termed nasal turbinates or CONCHAE TURBINATES (T)**. Nasal turbinates are composed of thin cores of **trabecular bone** (arrows) lined by stroma and epithelium. The nasal turbinates increase the area of contact of inhaled air with respiratory mucous membrane, thus regulating the quality and quantity of inhaled air. Although the majority of the surface area of the nasal cavity mucosa is respiratory epithelium, **portions of the more caudodorsal regions of the nasal cavity are covered by olfactory epithelium**; the **olfactory epithelium is specialized and facilitates the sense of smell**. Olfactory epithelium is a tall, pseudostratified epithelium that contains three distinct cell types: 1. 2. 3. Bowman's glands, also known as **olfactory glands**, play a **crucial role in the sense of smell**. The olfactory glands are **tubuloalveolar glands** located within the lamina propria--they open to the surface through ducts lined by cuboidal or flattened cells. These glands produce a mucus that lubricates the olfactory epithelium and dissolves odorant-containing gasses, facilitating their transport to the olfactory receptors.  In summary, the **nasal cavity is a bone-supported cavity within the skull divided by a cartilaginous septum into two halves: left and right. Each half consists of three regions**: 1. 2. 3. The **vomeronasal organs** are **paired (left and right) specialized chemoreceptor organs adjacent to the nasal septum within the nasal cavity of domestic species**. Structurally, the vomeronasal organ is a **thick layer of sensory epithelium partially encased by cartilage and associated with an abundant vascular supply**. Histologically, the sensory epithelium is similar to that of olfactory epithelium, with a **thick pseudostratified epithelium that contains three populations of cells**: **receptor cells, sustentacular cells, and basal cells**. The vomeronasal receptor cells, similar to olfactory receptor cells, are modified neurons that detect pheromones (e.g. pheromones in urine) and transmit to the brain via efferent axons. **Access of air to this region of the nasal cavity is facilitated through passage through ducts in the dorsal aspect of the oral cavity (roof) of some species by the behavioral action of the flehmen response**. This behavior looks different in different species. Examples include the curling of the upper lip in ungulates, chattering of the mouth in dogs (tonguing), and the open-mouthed posture of cats. Vomeronasal organ, dog. The vomeronasal organs (VNO) lie, bilaterally, within the rostral portion of the nasal cavity and are surrounded by cartilage (yellow arrow) and are highly vascularized (black arrow). **IMPORTANT: cartilage is very important for differentiating between trachea (dorsally incomplete rings of cartilage), bronchus (plates of cartilage) and bronchiole (no cartilage). Likewise, as you move down the respiratory tract, the number of goblet cells in the epithelium decreases.** **LARYNX** The larynx is a complex, tubular organ primarily composed of cartilage (hyaline + elastic) and skeletal muscle. The **larynx connects the naso- and oro-pharynx with the trachea**, functioning in air conduction, vocalization, and in obstructing passage of ingesta into the trachea during deglutition. The epithelium of the larynx is variable: it is generally **stratified squamous epithelium in the rostral segment**, but **ciliated pseudostratified columnar (respiratory) epithelium after the vocal cords**. The lamina propria below the laryngeal epithelium contains secretory glands. 6 **TRACHEA** The luminal (mucosal) surface of the **trachea is lined by ciliated, pseudostratified columnar epithelium** (i.e. respiratory epithelium) **interspersed with goblet cells**. The **lamina propria and submucosa** (not clearly demarcated) **also contain small mixed** (mucous and serous) **glands and smooth muscle**. The trachea is supported by a series of **C-shaped cartilaginous (hyaline cartilage) rings**. **Dorsally**, the ends of the **incomplete cartilaginous rings** of the trachea are **connected by a band of smooth muscle: the trachealis muscle**. Externally, the trachea is **surrounded by** a thin layer of fibrovascular connective tissue **(adventitia)**. NOTE: birds have complete rings of cartilage. **BRONCHI** Distally, the trachea divides into the **left and right mainstem bronchi**. Bronchi are histologically similar to the trachea. They are **lined by ciliated, pseudostratified columnar epithelium** (respiratory epithelium) and **interspersed with goblet cells**. The walls of bronchi are also supported by **cartilage plates** **(not rings). Bronchi have** **smooth muscle.** The smooth muscle of airways mediates bronchoconstriction, the process of contraction and subsequent narrowing of the airway lumen. Bronchoconstriction is mediated, in part, via mast cell-derived histamine, and massive histamine release (e.g. anaphylaxis) is life threatening. Finally, the **lamina propria of bronchi also contain moderate numbers of mixed glands** (**bronchial glands**). These are particularly abundant in cats. The mixed seromucous glands secrete mucin, lactoferrin and lysozyme (bacteriostatic/cidal).  As the bronchi extend deep into the pulmonary parenchyma, they continue to bifurcate, giving rise to smaller caliber (diameter) secondary and tertiary bronchi. Eventually, **bronchi give way to smaller conducting airways, bronchioles**. Bronchioles are **thin-walled airways lined by variably ciliated or nonciliated columnar epithelium**. The **walls are composed of tangentially arranged smooth muscle**. Bronchioles lack cartilage and glands which, along with their smaller size, distinguish them histologically from bronchi. Bronchioles are subdivided into **terminal** bronchioles and **respiratory** bronchioles (terminal bronchioles branch and continue as respiratory bronchioles).  The transition between regions of air conduction (i.e. bronchioles) and regions of air exchange (i.e. alveoli) in the lung progresses through sequentially distinct segments; from proximal to distal: terminal bronchioles, respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli. **TERMINAL BRONCHIOLES** Terminal bronchioles are lined by ciliated cuboidal or columnar cells with **few to no goblet cells**. In terminal bronchioles, a muscularis mucosae is present. Therefore, it **is possible to differentiate between the lamina propria and the submucosa in terminal bronchioles**.  BB = brush border; L = lumen; G = goblet cell; B = basal cell; LP = lamina propria; Ci = ciliated columnar epithelial cell; BM = basal membrane; F = fibrocyte; P = plasma cell; S = submucosa; CT = connective tissue; C = capillary; SM = smooth muscle **RESPIRATORY BRONCHIOLES** (best developed in cat and dog) Respiratory bronchioles are **lined by ciliated cuboidal epithelium** which i**ntermittently flattens distally, turning into alveoli**. The histologic appearance of respiratory bronchioles is similar to that of terminal bronchioles, with the exception that the epithelium is interrupted by alveoli. Respiratory bronchioles are lined by two types of epithelial cells: ciliated columnar cells and club cells (also known as Clara cells). **CLUB CELLS** are **bronchiolar exocrine cells located in terminal and respiratory bronchioles**--they **bulge at the surface** into the lumen of bronchioles. Club cells **DO NOT have cilia** on their apical surface, but do contain microvilli. Club cells serve **two main functions: secretory and metabolic**; they are the source of a surfactant-like substance which aids in maintaining patency of the airway and metabolize airborne toxins and xenobiotic compounds (may have some immune function). Respiratory bronchioles have an incomplete muscularis mucosae and **subdivide into alveolar ducts.** Respiratory bronchioles have an incomplete muscularis mucosae and **subdivide into alveolar ducts.** Alveolar ducts are composed of alveoli lined with simple squamous epithelial cells. On either side of the entrance into alveoli, knob-like projections of cuboidal epithelium covering small amounts of smooth muscle can be appreciated. Alveolar sacs are indistinct segments that open into individual alveoli. **Three main parts of the gas exchange system: alveolar sacs, alveolar ducts and alveoli.** Alveolar ducts have smooth muscle knobs, whereas alveolar sacs do [not] have smooth muscle, so that is how you can tell an alveolar duct from an alveolar sac on histology. Alveoli (singular: alveolus) are the site of gas exchange in the lung. Alveoli are **thin-walled, sac-like structures lined by a single layer of flattened squamous epithelial cells: type I pneumocytes (squamous alveolar type I)**. This **extremely thin nature** of the type I pneumocytes **facilitates gas exchange across their surface**. The **alveolar wall, or septum, consists of capillaries and minimal connective tissue support**. As such, alveolar septal capillaries are almost in direct apposition with the type I pneumocyte. The type I pneumocyte and capillary lumen are **separated only by the basement membrane of the type I pneumocytes, minimal or absent septal connective tissue, the basement membrane of the capillary endothelium, and the endothelial cells** themselves. This provides an extremely narrow gap through which gasses can diffuse, providing for efficient exchange of oxygen and carbon dioxide between alveolar spaces and capillaries. Type I pneumocytes are **not** mitotic, have occluding junctions to prevent fluid passage and their organelles are grouped around their nuclei. In addition to the type I pneumocytes, alveoli also contain **Type II pneumocytes (granular alveolar type II)**. Type II pneumocytes are **cuboidal epithelial cells frequently residing in the corners of alveolar spaces--**they account for 5% of alveolar surface area. Type II pneumocytes are **responsible for the secretion of surfactant.** Surfactant is a **fluid (composed of phospholipids and proteins) produced by lamellar bodies within the pneumocytes' cytoplasm that coats the surface of alveolar spaces to reduce surface tension**. By reducing surface tension, surfactant reduces the effort needed to inflate alveoli, thus preventing alveolar collapse (**atelectasis**). Cortisol stimulates production of surfactant in the fetus just prior to parturition (giving birth), therefore, it is very important for a fetus to have a well-developed adrenal gland--a fetus without an adrenal gland is nonviable. Absence of surfactant in newborns is known as *Hyaline Membrane Disease.* In addition, type II pneumocytes play a crucial role in tissue repair in the lung. Following damage to type I pneumocytes, **type II pneumocytes proliferate and differentiate into type I pneumocytes**, thereby restoring alveolar structure. **\***reminder: **two cells secrete surfactant/ surfactant-like: club cells and pneumocytes type II cells\***  Lung, dog. Alveolar type I pneumocytes are flattened squamous epithelium that line the majority of the alveolar surface area. Type II pneumocytes are frequently more plump to cuboidal, and are frequently located in the "corners" of alveoli. **PORES OF KOHN = ALVEOLAR SEPTAL PORES** Neighboring alveoli connect with each other via pores, providing equalization of pressure and collateral ventilation if a bronchiole is obstructed. Pores allow macrophage passage from one alveolus to another. Finally, **alveolar spaces contain a resident population of macrophages**, alveolar macrophages. Normally, these macrophages are located in close proximity to type I pneumocytes, and can be mistaken for type II pneumocytes. These macrophages, which are relatively low in number, **readily phagocytize debris within alveoli**, which can include surfactant, edema fluid, red blood cells, and pathogens (e.g. bacteria). Low numbers of macrophages are also normally present within the alveolar septal interstitium. Pores of Kohn (alveolar septal pores) allow macrophage passage from one alveolus to another. The macrophages are often referred to as **DUST CELLS = PULMONARY MACROPHAGES (PAMS)**  **INTERSTITIUM = EXTRACELLULAR MATRIX = STROMA** Interstitium is the space between cells as well as the microcirculation. It is composed of structural, adhesive and absorptive components collectively referred to as the extracellular matrix. **PULMONARY INTERSTITIUM** Pulmonary interstitium is the interconnecting network of interstitial stromal tissue supporting the blood and lymphatic vessels, nerves, bronchi, bronchioles and alveoli. 1. 2. 3. Pulmonary changes such as edema, emphysema, and inflammation, may affect one or more of these interstitial compartments. **INTRAVASCULAR MACROPHAGES (PIMS)**: **PULMONARY SEPTUM** Pulmonary septum is a dividing wall between alveoli composed of interstitium AND CELLS. Collagen type III is present in alveolar walls, while collagen type I is present in conducting airways. The alveolar septum and interstitium contain elastic fibers allowing the alveoli to stretch during inhalation and recoil during exhalation. BLOOD-AIR BARRIER 1. 2. 3. **oxygen pathway:** surfactant → cytoplasm of pneumocyte type 1 → basal lamina → cytoplasm of endothelial cell → capillary RBCs **Carbon dioxide pathway:** Capillary RBCs → cytoplasm of endothelial cell → basal lamina → cytoplasm of pneumocyte type 1 → surfactant **PULMONARY BLOOD SUPPLY - DUAL BLOOD SUPPLY** PULMONARY ARTERIES (arterioles) → functional blood supply (unoxygenated blood - low pressure) BRONCHIAL ARTERIES (from bronchoesophageal) → nutritional blood CAPILLARIES (continuous type) PULMONARY VEINS (oxygenated blood - low pressure) Lungs are covered by **visceral pleura** composed of **connective tissue** and **lined by** **simple squamous epithelial cells (mesothelial cells).** The **thoracic wall, diaphragm and mediastinum** are lined by the **parietal pleura** which is continuous with the mediastinal and visceral pleura. **PULMONARY INNERVATION**: 1. 2. **Contraction of smooth muscle (bronchi, bronchioles and vessels) is involuntary** DEFENSE MECHANISMS OF THE RESPIRATORY SYSTEM 1. a. b. c. d. 2. a. b. c. REACTION TO INJURY: Goblet cells are **present along the airways to the level of large bronchioles**; secretion traps particulate matter; **increased number of goblet cells** (hyperplasia) **in smokers**; **absence of goblet cells** due to metaplasia (**change from ciliated pseudostratified epithelium to squamous stratified epithelium**) results in **loss of immune function**. **PULMONARY EDEMA**: Pulmonary edema refers to the build up of fluid in the lungs (alveolar spaces filled with proteinaceous fluid); gas exchange cannot take place with fluid in the alveolar space.