د.عبد الجبار فالح Histology 2017-2016
The respiratory system is divided into two principle regions: a conductive part consisting of nasal cavity, nasopharynx, larynx, trachea, bronchi, bronchioles and terminal bronchioles and respiratory part (where gas exchange takes place), consisting of respiratory bronchiole, alveolar ducts and alveoli. Alveoli are saclike structures that make up the greater part of the lung, they are the main site for the principle function of the lung–the exchange of O2 and CO2 between the inspired air and blood.
The conductive part serves two main functions: to provide conduit through which the air can travel to and from the lungs and to condition the inspired air.
Figure 1: The main divisions of the respiratory tract. The natural proportions of these structures have been altered for clarity; the respiratory bronchiole, for example, is in reality a short transitional structure.
Most of the conductive part is lined by ciliated pseudostratified columnar epithelium with high number of goblet cells which is called a respiratory epithelium. Respiratory epithelium consist of five cell types: ciliated columnar cells (the most abundant one), beneath the cilia are basal bodies with numerous mitochondria, the next abundant cells are the goblet cells which contain mucous droplets, the remaining columnar cells are called brush cells which have microvilli at their apical ends, these cells have afferent nerve ending (so they are considered as sensory receptors), basal (short) cells are small, rounded that lie on the basal lamina and do not extend to the luminal surface of the epithelium, these are generative cells that undergo mitosis and differentiate into the other cell types, the last cell type is the small granular cells, which resemble the basal cells but these cells contain abundant cytoplasmic granules.
Figure 2. Photomicrograph illustrating the main components of the respiratory epithelium.
Immotile cilia syndrome: a disorder that causes infertility in men and chronic respiratory tract infections in both sexes, is caused by immobility of cilia and flagellum due to the deficiency of protein called Dynein, which is normally present in the cilia, Dynein participate in ciliary movement.
In smokers, the proportion of ciliated cells to goblet cells is altered, the greater number of goblet cells in smoker's epithelium provide for a more rapid clearance of pollutants, the reduction in ciliated cells caused by excessive intake of CO results in decreased movement of the mucous layer and frequently lead to congestion of smaller airways.
The nasal cavity consists of two structures: the vestibule and the nasal fossa.
*Vestibule: Is the most anterior and dilated part of the nasal cavity, the outer part is the nares, around the inner surface of the nares are sebaceous and sweat glands in addition to thick short hairs or vibrissae that filter out the large particle from the inspired air, the epithelium change its epithelium from keratinized into respiratory epithelium.
*Nasal fossa :
Within the skull lie two chambers separated by osseous nasal septum, in the lateral wall, there are three bony projections known as chonchae (superior, middle and inferior), the middle and inferior are covered by respiratory epithelium, the superior one is covered by olfactory epithelium. The narrow passages created by chonchae improve the conditioning of the inspired air and increase the surface area of respiratory epithelium, to increase the contact of inspired air with the mucous layer. Within the lamina propria of the chonchae are large venous plexus called the Swell bodies. Every 20-30 min, the swell bodies on one side of the nasal fossa are engorged with blood and result in distention of chonchal mucosa mucosa to decrease the air flow, at this time, most of the air is directed through the other nasal fossa, these periodical occlusions of nasal fossa enable the respiratory epithelium to recover for desiccation.
Allergic reaction and inflammation can cause abnormal engorgement of swell bodies in both fossae, severely restricting the air flow.
The nasal cavity has a rich vascular system, large vessels form close–meshed lattice work, from which arcading branches lead toward the surface, the blood directed against the flow of inspired air, so the incoming air is warmed by counter current system.
Olfactory epithelium is specialized area of mucous membrane in the roof of the nasal cavity. It is about 10 square cm in area. It is pseudostratified epithelium composed of three types of cells:
*The supporting cells: have broad, cylindrical apexes and narrow bases, on their free surface are microvilli submerged in a fluid layer. The supportive cells contain a light yellow pigment that responsible for the color of the olfactory mucosa.
*The basal cells: are small, spherical or cone–shaped at the base of epithelium.
Between the basal cells and supportive cells are the *olfactory cells–bipolar neurons, their nuclei are located below the nuclei of the supportive cells. Their apexes (dendrites) possess elevated and dilated areas from which six to eight cilia arise. These cilia are very long and nonmotile, they respond to odoriferous substances and generate an action potential. The afferent axons unite in small bundles and directed toward the brain to synapse with neurons of olfactory lobe.
The lamina propria of the olfactory epithelium possess the glands of Bowman's, their secretion produces a fluid around the olfactory cilia to clear the cilia, facilitate the access of new odoriferous substances.
Figure 3: Olfactory mucosa showing the 3 cell types (supporting, olfactory, and basal) and a Bowman’s gland.
Conditioning of Air:
The major function of the conductive part is to clean, moistened and warmed the inspired air before it enter the lungs, as the air enter the nose, large vibrissae remove coarse particles of dust, while particulate and gaseous impurities are trapped in a layer of mucous, this mucous and serous secretion also serve to moisten the incoming air. A rich superficial vascular network also warms the incoming air.
The respiratory system has an exceptionally large area that is exposed to both blood –borne microorganisms and the external environment, so it is not surprising that the respiratory system has several defense mechanisms. Particles larger than 10 µm are retained in the nasal passages, and particles of 2-10 µm are trapped by the mucous –coated ciliated epithelium. The cough reflex can eliminate these particles by expectoration or swallowing. Smaller particles are removed by the macrophages. In addition to those non specific mechanisms there are abundant lymphoid tissues in the bronchus containing B and T lymphocytes that are interact with macrophages. This important component of the immune system is called BALT (Bronchus Associated Lymphoid Tissue)
They are closed cavities in the frontal, maxillary, ethmoid and sphenoid bones, are lined with a thin respiratory epithelium. The lamina propria contains few glands, the paranasal sinuses communicate with the nasal cavity through small openings.
Is the first part of the pharynx, continuing caudally with the oropharynx, it is lined by respiratory epithelium in the part that is in contact with the soft palate.
Is an irregular tube that connects the pharynx to the trachea, in the lamina propria are number of cartilages, the larger sized are hyaline, the small sized are elastic. In addition to other supportive role, they serve as a valve to prevent the swallowed food or fluid to enter the trachea, also they are participated in sound production.
The epiglottis, which project into the pharynx from the rim of the larynx, has two surfaces lingual and laryngeal surfaces, the lingual one is covered with stratified squamous epithelium while in the laryngeal surface there is a transition into the respiratory epithelium.
Below the epiglottis, the mucosa form two pairs of folds, the upper pair called the false vocal cord (vestibular fold) covered by respiratory epithelium, the lower pair (true vocal cord) covered by stratified squamous epithelium, this cord contain bundle of elastic fibers called vocal ligament, parallel to it is skeletal muscle fibers called vocalis muscle which regulate the tension of vocal cords.
Trachea is lined with respiratory epithelium, the lamina propria contain 16-20 C-shaped rings of hyaline cartilages, seromucous gland. A fibro elastic ligament and bundle of smooth muscles bridge the open ends of these C-shaped cartilages, this ligament prevent over distension of the lumen, the smaller bore of the trachea after contraction provides for increase velocity of expired air ( to clear the air passages).
The trachea divided into two primary bronchi that enter the lung at the hilum, the primary bronchi giving rise to three bronchi in the Rt and two in the Lt which supplies the pulmonary lobes, these lobar bronchi divides and give rise to smaller branches called bronchioles, each of which enter the pulmonary lobule, its branches divide to form 5-7 terminal bronchioles. The pulmonary lobules are pyramidal in shape. Each one is delineated by a thin connective tissue.
The primary bronchi have the same histological criteria as the trachea. Proceeding toward the respiratory part, the histological features become simple. This simplification is gradual, no abrupt transition.
Each primary bronchus branches 9-12 times until it reach a diameter < 5mm, the mucosa is similar to that of trachea, in the larger parts. The cartilage rings completely encircle the lumen. As the bronchial diameter decrease, the cartilage rings are replaced with isolated plates of hyaline cartilage. Beneath the epithelium are bundles of spirally arranged smooth muscle. The lamina propria is rich in elastic fibers and contains abundant serous and mucous glands.
Bronchioles have a diameter of 5 mm or less, have neither cartilage nor glands, there are scattered goblet cells. In the larger bronchioles, the epithelium is ciliated pseudostratified columnar which decrease in height toward the smaller bronchioles to become ciliated simple columnar or cuboidal epithelium. The terminal bronchioles contain Clara cells which devoid from cilia and contain secretary granules that secrete proteins which protect the epithelium lining from the oxidative pollutants and inflammation. Lamina propria composed largely of smooth muscles and elastic fibers. Stimulation of vagus nerve decreases the diameter of these structures while sympathetic stimulation increases the diameter of the bronchioles.
Figure 4: Transition of a terminal bronchiole into an alveolar duct (arrow). Note the Clara cells (arrowheads).
Each terminal bronchiole subdivides to give the respiratory bronchioles which is a region of transition between the conductive and the respiratory portion, the mucosa is identical to that of terminal bronchioles except that their wall are interrupted by saclike alveoli, portion of respiratory bronchioles are lined with ciliated cuboidal epithelium with Clara cells, but at the rim of alveolar opening, the bronchiolar epithelium continuous with squamous alveolar cells, distally along the respiratory bronchiole more and more alveoli are opened into them, the epithelium become non ciliated in the distal part, smooth muscle and elastic fibers lie beneath the epithelium.
Figure 5: Section of a terminal bronchiole with a small portion of a respiratory bronchiole continuous with an alveolar duct and many alveoli. PT stain. Low magnification.
Proceeding distally along the respiratory bronchioles the number of alveolar opening will be higher until the wall consists of nothing else ,and the tube is now called the alveolar duct, both of alveolar ducts and alveoli are lined with attenuated squamous epithelium .The lamina propria contain network of smooth muscle which disappear at the distal end of the alveolar ducts. A rich matrix of elastic and reticular fibers provides the only support to the alveolar duct and alveoli.
Alveolar ducts open into the atria which communicate with the alveolar sacs, elastic and reticular fibers form a complex network that encircle the alveolar ducts, atria and the alveoli, the elastic fibers enable the alveoli to expand during inspiration and to contract during expiration. Reticular fibers prevent over distension and damage to delicate capillaries and thin alveolar septum.
Alveoli are saclike evaginations of the respiratory bronchioles, alveolar ducts and alveolar sacs. Alveoli are responsible for the spongy structure of the lungs. Within these structures, O2 and CO2 are exchanged between the air and the blood. The structure of the alveolar wall is specialized for enhancing diffusion between the internal and external environment. Each wall lies between two neighboring alveoli is called interalveolar septum which consist of two thin squamous epithelial layers between which lie capillaries, elastic and reticular fibers and connective tissue cells (fibroblasts, macrophages and leukocytes) and matrix.
Air in the alveoli is separated from capillary blood by three components referred to collectively as the blood air barrier: the surface lining and the cytoplasm of the alveolar cells, the fused basal laminae of the alveolar and endothelial cells, and the cytoplasm of the endothelial cells. The total thickness of these layers ranged from 0.1 -1.5µm.
Figure 6: Portion of the interalveolar septum showing the blood-air barrier. To reach the erythrocyte, O2 traverses the surface lining, the alveolar epithelium cytoplasm, and the plasma. In some locations, there is loose interstitial tissue between the epithelium and the endothelium.
Capillary endothelial cells are extremely thin, the endothelial lining of the capillaries is continuous and not fenestrated, there are numerous pinocytotic vesicles in the cytoplasm.
Type I cells, or squamous alveolar cells are extremely attenuated cells that line the alveolar surfaces (make up 97% of the alveolar surfaces), type II make the remainder 3%. Organelles such as Golgi complex, endoplasmic reticulum and mitochondria are grouped around the nucleus, reducing the thickness of the blood air barrier. The cytoplasm in the thin portion contains abundant pinocytotic vesicles, which play a role in turn over of surfactant and the removal of contaminants from the outer surface. There are desmosomes and occluding junctions between these cells that prevent the leakage of tissue fluid into the alveolar space. The main role of these cells is to provide a barrier of minimal thickness that is readily permeable to gases.
Type II cells:
These cells are interspersed among type I cells. They are rounded and usually found in groups of two or three at angles. These cells rest on basement membrane. In histological appearance they exhibit vesicular or foamy cytoplasm. These vesicles are caused by the presence of lamellar bodies. Histochemical studies show that these bodies which contain phospholipids, glycosaminoglycans and proteins are continuously synthesized and released at the apical surface of the cells. The lamellar bodies provide an extracellular alveolar coating, pulmonary surfactant, which lower alveolar surface tension. The reduction of surface tension means that less inspiratory force is needed to inflate the alveoli, and thus the work of breathing is reduced. In addition without surfactant, alveoli would tend to collapse during expiration. In fetal development, surfactant appears in the last weeks of gestation and coincides with the appearance of lamellar bodies in the type II cells.
The surfactant layer is not static but is constantly being turned over, is removed from the surface by the pinocytotic vesicles of the squamous epithelial cells, by macrophages and by type II cells.
Figure 7: Secretion of surfactant by a type II cell. Surfactant is a protein-lipid complex synthesized in the rough endoplasmic reticulum and Golgi complex and stored in the lamellar bodies. It is continuously secreted by means of exocytosis (arrows) and forms an overlying monomolecular film of lipid covering an underlying aqueous hypophase. Occluding junctions around the margins of the epithelial cells prevent leakage of tissue fluid into the alveolar lumen.
Alveolar lining fluids are also removed via the conducting passages as a result of ciliary activity. As the secretion pass up it combine with bronchial mucous to form what's called bronchoalveolar fluid which aid in removal of particulate and noxious substances that are inspired with air, this fluid contain several lytic enzymes that are probably derived from macrophages.
The respiratory distress syndrome of newborn is a life threatened condition of the lung caused by a dificiancy od surfactant. It is principally associated with prematurity. The incidence of respiratory distress syndrome varies inversely related with gestational age. The immature lung is deficient in both the amount and composition of surfactant. In the respiratory distress syndrome the alveoli are collapsed and the respiratory bronchioles and alveolar ducts are dilated. Recently, surfactant has also been suggested to have bactericidal action, aiding in the removal of potentially dangerous bacteria that reach the alveoli.
Alveolar macrophages also called dust cells are found in the interalveolar septum. The phagoctosed debris within these cells was most likely passed from the alveolar lumen into the interstitium by the pinoctyotic activity of type I alveolar cells.
The interalveolar septum contain pores that connect neighboring alveoli, these pores equalize air pressure in the alveoli and promote the collateral circulation of air when a bronchiole is obstructed.
Figure 8: Three-dimensional schematic diagram of pulmonary alveoli showing the structure of the interalveolar septum. Note the capillaries, connective tissue, and macrophages. These cells can also be seen in—or passing into—the alveolar lumen. Alveolar pores are numerous. Type II cells are identified by their abundant apical microvilli. The alveoli are lined with a continuous epithelial layer of type I cells.
Pulmonary blood vessels:
Circulation in the lungs include both nutrient (systemic) and functional (pulmonary) vessels. Within the lungs the pulmonary arteries branches accompanying the bronchial tree. At the level of the alveolar ducts, the branches of these arteries form a capillary network in the interalveolar septum and in close contact with the surface epithelium.
Venules that originate in the capillary network are supported by a connective tissue and enter the interalveolar septum then they follow the bronchial tree toward the hilum.
Nutrient vessels follow the bronchial tree and distribute blood to most of the lung up to respiratory bronchioles at which point they anastomose with small branches of the pulmonary artery.
Pulmonary lymphatic vessels:
The lymphatic vessels follow the bronchi and pulmonary vessels, they are found in the interlobular septum and all drain into regional lymph nodes. This lymphatic vessels is called deep network to distinguish them from superficial network which include the lymph vessels in the pleura. The lymphatic vessels are not found in the terminal portions of the bronchial tree or beyond the alveolar ducts.
The pleura is the serous membrane covering the lungs. It consists of two layers, parietal and visceral which become continuous at the region of hilum. Both membranes are composed of mesothelial cells resting on a fine connective tissue layer that contain elastic and collagen fibers. The parietal and visceral layers define a cavity lined with squamous mesothelial cells, under normal condition, this pleural cavity contain only a film of liquid that act as a lubricant facilitating the smooth sliding of one surface over the other during respiratory movements.
Figure 9: Blood and lymph circulation in a pulmonary lobule. Both vessels and bronchi are enlarged out of proportion in this drawing. In the interlobular septum, only one vein (on the left) and one lymphatic vessel (on the right) are shown, although both actually coexist in both regions. At the lower left, an enlargement of the pleura shows its mesothelial lining.