Lesson 22 - Respiratory System (notes) PDF

Cytology and Histology _____________ Lesson 22 _____________ RESPIRATORY SYSTEM The respiratory system has as its main function the exchange of gases (O2 and CO2) between the body and the environment and is constituted by the conductive airways, which are the nasal cavity, the nasopharynx, the lar...

Cytology and Histology _____________ Lesson 22 _____________ RESPIRATORY SYSTEM The respiratory system has as its main function the exchange of gases (O2 and CO2) between the body and the environment and is constituted by the conductive airways, which are the nasal cavity, the nasopharynx, the larynx, the trachea, the bronchi and the bronchioles and by an area of gas exchange formed by the respiratory bronchioles, the alveolar ducts and the respiratory alveoli. The conductive airways, in addition to conveying the air to the alveoli, have other functions such as heating the inspired air, its saturation up to 100% relative humidity and the filtration and retention of gases, particles and harmful microorganisms. I. CONDUCTIVE AIRWAYS 1. Nasal cavity It is made up of a mucosa that rests on the perichondrium and periosteum of the cartilage and bones, respectively, of the head. It communicates the nasopharynx with the outside of the body and is composed of three regions: the nasal vestibule, the respiratory region and the olfactory region. Nasal vestibule It is the most rostral region of the nasal cavity and continues with the skin of the nostrils. In its most rostral region, the nasal vestibule is lined by a pigmented keratinized stratified squamous epithelium; in the middle part, by a non-keratinized stratified squamous epithelium and, in the caudal portions, the epithelium becomes pseudostratified non-ciliated columnar, showing microvilli in the apical border of the cells, but not cilia. The lamina propria is made up of a loose vascularized connective tissue with serous glands. Respiratory region It occupies most of the nasal cavity, including the rostral and middle part of the nasal septum and the nasal turbinates. The mucosa presents a pseudostratified ciliated columnar epithelium (respiratory epithelium) in which five types of cell populations are distinguished. 1. Basal cells: their shape varies from triangular to columnar, they are located at the base of the epithelium and are attached to the basement membrane by hemidesmosomes. They can divide and differentiate into other populations of epithelial cells, which they replace when they wear out. Cytology and Histology 2. Ciliated epithelial cells: these are columnar cells with numerous cilia (200 to 300) and microvilli in the apical portion. They present a nucleus in the basal portion, an evident Golgi complex, in a supranuclear position, numerous rough endoplasmic reticulum cisternae, free ribosomes, and mitochondria. 3. Secretory cells: there are two types. a. Serous cells: with a large number of rough endoplasmic reticulum cisternae, very evident Golgi complex and electron-dense granules, in the apical portion, containing neutral glycoproteins. b. Mucous cells: goblet cells that synthesize mucinogen and accumulate it in the apical part of the cell, distending it. This displaces the nucleus and the organoids (Golgi complex and rough endoplasmic reticulum cisterns) to the basal part of the cell. The mucinogen is made up of acidic glycoproteins. 4. Brush cells: they are columnar cells that contain long and thick microvilli in their apical portion. They present synapses with nerve cells, which makes some authors to consider them as sensory receptor cells associated with trigeminal nerve endings. 5. Non-ciliated cells: they are columnar, with abundant microvilli (but NOT cilia) in the apical portion and a highly developed smooth endoplasmic reticulum. The function of these cells is to metabolize toxic substances that enter with the inspired air. The lamina propria is made up of highly vascularised loose connective tissue, especially in the caudal regions, where a cavernous stratum is distinguished with numerous tortuous and dilated venous sinuses. In addition, there are tubulo-acinar seromucous glands that produce lysozyme and enzymes to metabolize fat-soluble exogenous toxins. Figure 1: Pseudostratified ciliated columnar epithelium with goblet cells. MO. Olfactory region The mucosa is lined by a pigmented olfactory epithelium, a variant of the pseudostratified ciliated columnar epithelium, made up of three cell populations. The olfactory region occupies the ethmoturbinates and the caudodorsal area of the nasal cavity and nasal septum. 1. Basal cells, similar in morphology to those previously described. Cytology and Histology 2. Olfactory neurosensitive cells. They are bipolar neurons with the perikaryon or soma located in the basal area of the epithelium. The dendritic zone ends up forming an expansion called the dendritic bulb, in the lumen. This bulb contains 10 to 30 cilia with a special structure and numerous vesicles. Cilia have excitatory chemoreceptors for odorous substances. For their part, the axons of these cells cross the lamina propria as unmyelinated nerve fibres and constitute the olfactory nerve that reaches the olfactory bulb of the brain through the ethmoid lamina cribrosa. 3. Supportive cells. They are columnar cells interposed between the neurosensitive ones. They have microvilli in the apical portion, a vesicular nucleus in the basal portion, and modes of junction with neighbouring olfactory cells. The cytoplasm has a well-developed Golgi complex, numerous rough endoplasmic reticulum cisterns, smooth endoplasmic reticulum vesicles, and electron-dense pigment-containing granules that give the olfactory mucosa a brownish coloration. The lamina propria is made up of loose connective tissue with numerous tubuloacinar seromucous glands (Bowman’s glands). Its function is to moisten the surface of the epithelium and eliminate odorous substances from the cilia of the neurosensitive olfactory cells. 2. Trachea It is a tubular organ that communicates the larynx with the bronchi. The trachea is made up of a mucosa, submucosa, followed by a layer of hyaline cartilage and muscularis (smooth muscle) and an adventitia or serosa (depending on its organic location). I. Mucosa: lined by a pseudostratified ciliated columnar epithelium that rests on a loose connective tissue (lamina propria/submucosa) since there is no muscularis mucosae. The epithelium has the same cells described above for the respiratory epithelium but two more cell populations are added: Club cells (formerly Clara cells): they present electron-dense granules that contain neutral glycoproteins. These cells have abundant mitochondria, numerous RER cisterns, and a highly developed SER. They are secretory cells and metabolize toxic substances. Neuroendocrine cells (APUD system): They are pyramidal in shape, with argyrophilic secretion granules, numerous rough endoplasmic reticulum cisterns, evident Golgi complex, and free ribosomes. The lamina propria and the submucosa are made up of vascularized connective tissue with many elastic fibers and more abundant tubuloacinar seromucosal glands in the proximal regions of the trachea. II. Muscularis and hyaline cartilage layer: tracheal cartilages are shaped like the letter “U” or “C”, they are incomplete, except in birds, and they are made up of hyaline cartilage. In the dorsal region there are smooth muscle fibers that fuse with the perichondrium and that join the two ends of the cartilaginous ring. III. Adventitia or serosa: surrounding all these layers there is an adventitial tunic (connective tissue) or serosa (connective tissue plus mesothelium), depending on the organic location, neck or thoracic cavity, respectively. 3. Bronchial tree When the trachea enters the thoracic cavity it branches to give rise to the extrapulmonary bronchi. These bronchi are called main bronchi and are found in all Cytology and Histology species, while ruminants and pigs also have a tracheal bronchus. The extrapulmonary bronchi penetrate the right and left lungs through their hilum, dividing successively to give rise to numerous branches of the airways that can be grouped into 1. Primary and secondary intrapulmonary bronchi, 2. Bronchioles and 3. Respiratory or terminal bronchioles. • Extrapulmonary bronchi: have similar characteristics to the trachea. • Primary and secondary intrapulmonary bronchi: made up of four concentric layers. I. Mucosa: lined by a pseudostratified ciliated columnar epithelium (with Club or Clara cells and neuroendocrine cells) resting on loose connective tissue. There is also a muscularis mucosae, composed of smooth muscle fibers that are oriented in a spiral. II. Submucosa: thin, made up of connective tissue and tubuloacinar glands of seromucosal type. III. Cartilage/muscularis: cartilaginous rings decrease in thickness and discontinuous cartilaginous sheets are formed. As cartilage decreases, smooth muscle increases. IV. Adventitia, which is connective tissue with blood vessels, lymphatics, nerves, and lymphoid follicles. The latter constitute the bronchi associated lymphoid tissue (BALT) that is very evident in pigs. • Bronchioles: They are branches of the secondary bronchi. In them, the epithelium becomes a simple columnar or cuboidal epithelium consisting mainly of ciliated cells and Club cells and without goblet cells. The lamina propria and the submucosa are thin, with no muscularis mucosae. In addition, there is a muscularis of smooth muscle fibres with a circular or oblique orientation, and lack of cartilage. Figure 2: (A) Trachea showing ciliated columnar pseudostratified epithelium, highly vascularized lamina propria/submucosa, and intensely basophilic hyaline cartilage. LM. (B) Bronchus (*) showing hyaline cartilage and lymphoid tissue associated with bronchi and a bronchiole (arrow). LM. II. GASEOUS EXCHANGE AREA: PULMONARY LOBULE The pulmonary lobule is the functional unit of the lung and is made up of 1. respiratory bronchioles, 2. alveolar ducts, 3. atrium, 4. alveolar sacs and 5. respiratory alveoli. 1. Respiratory bronchiole: it is made up of a simple cuboidal epithelium with very few cilia and Club cells that rests on bands of smooth muscle and elastic fibres. In the respiratory bronchiole, the proportion of ciliated cells decreases and that of Club cells increases. Sacculiform dilations appear on its wall, which are respiratory alveoli lined by a simple squamous epithelium. The two functions of the respiratory bronchiole are thus air conduction and gas exchange. Cytology and Histology Figure 3: Diagram of the components of the pulmonary lobule. 2. Alveolar duct: its structure is the same as that of the respiratory bronchiole but the alveoli are more numerous, so that at the entrance of these there are smooth muscle and elastic fibres that are arranged as a sphincter called the "alveolar rim". The epithelium between alveoli consists only of Club cells. 3. Alveolar sacs and respiratory alveoli. Each alveolar duct ends in 3 to 6 alveolar sacs, which all have a common space as a vestibule called atrium. The alveolar sacs have secondary sacculations on their wall, which are respiratory alveoli. These are lined by an epithelium with two cell types (type I pneumocytes and type II pneumocytes) that rest on a basement membrane. Type I pneumocytes: these are squamous cells that line 97% of the alveolar surface. Through their cytoplasm they diffuse respiratory gases. These cells have a prominent nucleus, an elongated cytoplasm, few organoids, and especially micropinocytosis vesicles. In their lateral portion they differentiate modes of junction that link type I pneumocytes to each other and to type II pneumocytes. Figure 4: Type II pneumocyte. TEM. Type II pneumocytes: these are cuboidal cells that line 3% of the alveolar surface. They produce the lung surfactant that coats the alveolar epithelial lining surface. This pulmonary surfactant is continuously produced by type II Cytology and Histology pneumocytes and, according to recent evidence, is phagocytosed by the same cells that secrete it and by alveolar macrophages, which will be discussed later on. In addition, type II pneumocyte can divide by mitosis to regenerate itself and the type I pneumocyte. Type II pneumocytes are cuboidal cells, with a central nucleus, abundant organoids (mitochondria, RER, and evident Golgi complex) and microvilli on their apical surface. The most characteristic feature of these cells is the presence of secretory granules called dense laminar bodies because they have a concentric lamellar substructure. These granules contain phospholipids, mucopolysaccharides, and proteins. The secretion of the granules is the precursor of the surfactant, and its content is shed by exocytosis. The pulmonary surfactant prevents the alveoli from collapsing after expiration. Inside the alveoli we find a third type of cell, the pulmonary alveolar macrophages (PAMs), normally resting on type I pneumocytes. Their function is defensive, since they engulf particles of the inspired air, dust, toxins, etc. The lumen of two neighbouring alveoli is separated by the interalveolar septum, which is made up of highly vascularized thin connective tissue called the interstitium. In some species (pigs, ruminants, cats and rabbits), a fixed macrophage population has been described within the septal capillaries (located in the interstitium) of the lung. These macrophages are called pulmonary intravascular macrophages (PIMs). They are flattened cells, with pseudopods and different modes of junction with the capillary endothelium. The function of these macrophages is to eliminate toxins that reach the lung via the bloodstream. In the interalveolar septum there are from 1 to 6 holes or solutions of continuity that connect two neighbouring alveoli and are called alveolar pores. They have a diameter of between 7 and 9 µm and are lined by type I pneumocytes. Elastic and reticular fibres are arranged under this epithelium. The alveolar pores have two functions: to balance alveolar pressures so that the filling of the lung is homogeneous and to be a collateral circulation pathway, in case any conductive pathway is obstructed. The disadvantage of the existence of these alveolar pores is that they can be a pathway for the spread of pathogenic microorganisms. Thus, the respiratory gases to pass from the alveolar lumen to the capillary and vice versa must cross the so-called alveolar-capillary or haemato-air barrier, which is made up of: 1. Lung surfactant 2. Cytoplasm of type I pneumocyte 3. Basement membrane of the alveolus 4. Gap layer 5. Basement membrane of the septal capillary 6. Cytoplasm of the capillary endothelial cell The area of the thinnest alveolocapillary barrier, which is where the type I pneumocyte is in close contact with the capillary endothelium, is the most efficient point for oxygen exchange. This most efficient blood-air barrier is made up of: 1. Lung surfactant 2. Cytoplasm of type I pneumocyte 3. Basement membranes of the alveolus and the septal capillary fused 4. Capillary endothelial cell cytoplasm Cytology and Histology III. PLEURA It is made up of two sheets, one parietal, which lines the wall of the thoracic cavity and the other visceral, which lines the lung surface. The pleura is a serous membrane made up of loose connective tissue, widely irrigated and innervated and lined by a mesothelium. The connective tissue of the pleura continues into the lung with partitions that constitute the interlobular septae. Figura 6: Pleura y septo (flecha). MO. IV. ADDITIONAL INFORMATION: PARTICULARITIES OF THE BIRD'S RESPIRATORY SYSTEM The avian nasal cavity is lined by a mammalian-like epithelium, with rostrally stratified squamous epithelium, caudodorsal olfactory epithelium, and respiratory epithelium covering most of the remainder. Among the most striking differences with mammals, the presence of a greater number of lymphocytes in the avian respiratory system stands out, as well as the existence in birds of groups of goblet cells forming intraepithelial glands. The avian larynx produces few sounds because it does not have vocal folds. The trachea of birds is similar in structure to that of mammals except that the tracheal cartilage in birds forms complete rings, the tracheal muscle is absent, and the intraepithelial glands are numerous. Due to differences in cartilage structure and smooth muscle content, the avian trachea does not undergo phasic changes in diameter during respiration. The syrinx is the part of the avian respiratory system where vocalisation occurs. It is made up of numerous (tympanic) membranes lined by a stratified squamous epithelium that vibrate during sound production. It is located at the tracheobronchial junction. The main or extrapulmonary bronchi continue into the lung as primary intrapulmonary bronchi or mesobronchi, each of which ends up opening into an abdominal air sac. The epithelium that lines the mesobronchium is similar to that of the trachea, but the cartilage is not complete. The secondary bronchi come from the mesobronchi and many of them open into other air sacs. These bronchi present a simple columnar ciliated epithelium with goblet cells, and in their lamina propria smooth muscle bands that are arranged in a spiral, there is no cartilage in their wall. The tertiary bronchus, parabronchus or pulmonary tube is the third generation of bronchi and presents a simple non-ciliated cuboidal epithelium. In the lamina propria of the parabronchi there is a network of smooth muscle that forms spiral bands. In these bronchi, many small air spaces open, which are called atria. Cytology and Histology In the avian lung, gas exchange occurs between blood capillaries and air capillaries. The latter are sacculations 5 to 15 µm in diameter that open directly into the atrium. Most of the atria and air capillaries are lined by a simple squamous epithelium. The epithelial gas exchange zone consists of squamous and cuboidal cells similar to those of mammals. In birds there is also a biphasic acellular layer covering it, similar to the lung surfactant of mammals. The air sacs are lined by a simple epithelium, ranging from squamous to cuboidal.