Respiratory tract, anatomy

Local host defenses of both the upper and lower respiratory tract, along with the anatomy of the airways, are important in preventing infection. Upper respiratory defenses include the mucodliary apparatus of the nasopharynx, nasal hair, normal bacterial flora, IgA antibodies, and complement. Local host defenses of the lower respiratory tract include cough, mucodliary apparatus of the trachea and bronchi, antibodies (IgA, IgM, and IgG), complement, and alveolar macrophages. Mucus lines the cells of the respiratory tract, forming a protective barrier for the cells. This minimizes the ability of organisms to attach to the cells and initiate the infectious process. The squamous epithelial cells of the upper respiratory tract are not ciliated, but those of the columnar epithelium of the lower tract are. The cilia beat in a uniform fashion upward, moving particles up and out of the lower respiratory tract. 

Patra, A.L., "Comparative Anatomy of Mammalian Respiratory Tracts The Nasopharyngeal Region and the Tracheobronchial Region," J. Tox. Env. Health... 

Relative to body weight, humans have a much lower respiratory rate and cardiac output than rodents. These are the two primary determinants of systemic uptake of volatile chemicals. Therefore, at similar nominal concentrations, rodents absorb substantially more cyanide than primates. From a pharmacokinetic view, lower hepatic rhodanese levels in primates will not be significant at high, acute HCN exposures. It should be noted that Barcroft s subject withstood a 1 min and 31 s exposure at approximately 500 to 625 ppm without immediate effects (Barcroft 1931), whereas mice suffer asphyxia during a 2 min exposure at 500 ppm (Matijak-Schaper and Alarie 1982). Compared with rodents, the respiratory tracts of humans and monkeys are more similar in gross anatomy, the amount and distribution of types of respiratory epithelium, and airflow patterns (Barrow 1986 Jones et al. 1996). 

Davis, C.N. (1961). A formalized anatomy of the human respiratory tract. In Inhaled Particles and Vapours. (Davis, C.N., Ed.). Pergamon Press, London, pp. 82-91. 

Chediak AD, Wanner A (1990) The circulation of the airways anatomy, physiology and potential role in drug delivery to the respiratory tract. Adv Drug Deliv Rev 5 11-18. 

The underpressure created in the respiratory tract is the driving force for the airflow through an inhalation device. The attainable underpressure and the rate of the airflow both depend on the total resistance in the airways and inhaler. The pressure drop achieved during inhalation is furthermore a function of the anatomy of the lungs, the effort made by the patient, pathological factors and the presence of exacerbations (e.g. in case of asthma). 

For more detailed information on the respiratory tract, the pleura, and the lymphatic system, consult Gray s Anatomy or other standard medical texts. A comprehensive review of the lung and its structure and function is presented in Nagaishi (1972). 

The respiratory tract is exposed to chemicals in the inspired air. The two main factors that determine the tissue responses to chemicals are the functional anatomy of the respiratory tract and the physicochemical nature of the material. ... 

Nasal anatomy and physiology. The nose is the first organ of the respiratory tract. The structure of the nasal cavity is shown in Fig. 2.8. 

Anatomy and physiology. The human respiratory system is divided into upper and lower respiratory tracts. The upper respiratory system consists of the nose, nasal cavities, nasopharynx, and oropharynx. The lower respiratory tract consists of the larynx, trachea, bronchi, and alveoli, which are composed of respiratory tissues. 

The upper respiratory tract, particularly the nose, has a unique anatomy that performs normal physiologic functions as well as innate defense against inhaled toxicants. The nose extends from the nostrils to the pharynx. Inspired air enters the nose through the nostrils. The nasal cavity is divided longitudinally by a septum into two nasal compartments. In most mammalian species, each nasal cavity is divided into a dorsal, ventral, and middle (lateral) meatus by two turbinate bones, the nasoturbinate and maxilloturbinate. These turbinates project from the dorsolateral and ventrolateral wall of the cavity, respectively. In the posterior portion of the nose, the ethmoid recess contains the ethmoturbinate. The nasal cavity is lined by a vascular mucosa that consists of four distinct types of epithelia. In rodents, these epithelia are (1) the stratified squamous epithelium that lines the nasal vestibule and the floor of the ventral meatus in the anterior portion of the nose (2) the non-ciliated, pseudostratified, transitional epithelium that lies between the squamous epithelium and the respiratory epithelium and lines the lateral meatus (3) the ciliated respiratory epithelium that lines the remainder of the nasal cavity anterior and ventral to the olfactory epithelium and (4) the olfactory epithelium (neuroepithelium) that lines the dorsal meatus and ethmoturbinates in the caudal portion of the nose. The relative abundance and exact locations of these upper respiratory epithelium differ among mammalian species. 

Figure 27.3. Anatomy of the olfactory apparatus in the nasal cavity of the upper respiratory tract. (Adapted from Life ART illustration series, Lippincott Williams Wilkins, Hagerstown, MD, 1994. This figure was completely redrawn by the author from materials cited.)...

While chemical composition is important in determining the toxicity of particles and fibers, it is equally or more important to determine where a particle or fiber will deposit in the respiratory tract and how long it will stay there. The quantity and location of particle deposition in the respiratory tract depends on factors related to both the exposed individual and the inhaled particles. The mechanism of deposition is determined by the physical (size, shape, and density) and chemical (hygroscopicity and charge) characteristics of the inhaled particles. Particle deposition is also affected by biological factors inherent to the exposed individual such as breathing pattern (volume and rate), route of breathing (mouth versus nose), and the anatomy of the airways. 

The methods the USEPA uses in the derivation of inhalation RfDs are similar in concept to those used for oral RfDs however, the actual analysis of initiation exposures is more comple.x tlian oral e. posurcs due to (1) the dynamics of the respiratory system and its diversity across species, and (2) difTcrcnces in the physiochcmical (both physical and chemical) properties of contaminants. Although the identification of the critical study and the determination of the NOAEL in theory are similar for oral and inlralalion e.xposures, several important differences should be noted. In selecting the most appropriate study, the USEPA considers differences in respiratory anatomy and physiology, as well as differences in the physicochemical characteristics of tire contaminant. Differences in respiratory anatomy and physiology may affect the pattern of contaminant deposition in the respiratory tract, and the clearance and redistribution of the agent. Consequently, the different species may not receive the same dose of the contaminant at the same locations within the respiratory tract even though both species were exposed to the same particle or gas concentration. Differences in the physicochemical characteristics of the contaminants, such as the size and shape of a particle or whether the contaminant is an aerosol or a gas, also influence deposition, clearance, and redistribution. 

Lung cell cultures can provide mechanistic insights but they do not represent the complexity in the delivery and disposition of drugs in the human respiratory tract. Perfused lung organ studies provide the next level in complexity. Various animal models have been used with the view to predict quantitatively absorption of peptides and proteins from the human lungs. However, due to the major differences in the anatomy and physiology of respiration in primates, the predictive power of these models is quite limited as evidenced by the data in Fig. 2. (Animal models are, of course, essential in the assessment of safety and they can provide valuable mechanistic information.)... 

FIGURE 2.37 Thoracic duct and other vessels of the thorax. Lymphatic capillaries are most numerous just beneath body surfaces, such as the skin and the mucus membranes of the gastrointestinal and respiratory tracts. The mucus membrane of the gastrointestinal tract is called the gut mucosa. The general function of these capillaries is to absorb interstitial fluid that has leaked from the circulatory system and to return it to the bloodstream. The function of the l)miphatic capillaries that end in the lacteals of the small intestine is to transport absorbed dietary lipids. These capillaries coalesce and eventually deliver their contents to the thoracic duct. The lymph collected from other parts of the body, as indicated by the "collecting trunk," also is transferred to the thoracic duct. [Redrawn with permission, from "Grant s Atlas of Anatomy," Williams Wilkins Co., Baltimore, 1978.]... 

Figure 3 The anatomy of the respiratory tract from trachea to alveolus. (Reproduced from Smith RP (1992) The anatomy of the respiratory tract from trachea to alveolus. A Primer of Environmental Toxicology, p. 67. Philadelphia Lea Febiger, with permission from Lea Febiger.)...

The morphology of the specific respiratory tract region at both the gross anatomical and the microscopic levels is an important factor. In extrapolating animal effects to the human, one must be aware that the respiratory tract structure will vary both within individuals and between species at each level of anatomy. 

In considering the mechanisms of aerosol deposition within the lung and the factors that may influence them, it is of some importance to consider first the anatomy and air velocities within the respiratory tract. The temporal aspects of the passage of air through the various anatomic regions and the point during the breathing cycle are also relevant factors. 

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