It must accomplish all of these demanding tasks continuously over a lifetime, and do so with high efficiency in terms of performance and energy utilization.The system can be abused and overwhelmed by severe insults such as high concentrations of cigarette smoke and industrial dust, or by low concentrations of specific pathogens which attack or destroy its defence mechanisms, or cause them to malfunction.Aqueous solubility of bulk materials is a poor guide to particle solubility in the respiratory tract.
Importantly, 52 INH-sensitive isolates, selected to reflect the geographic and genotypic diversity of the isolates, were also included for comparison.
The kat G S315T substitution and fab G1-inh A -15 C-to-T mutation were identified in 34 and 13 of the 52 INH-resistant isolates, respectively, and none of the INH-sensitive isolates.
The deposited particles can damage the epithelial and/or the mobile phagocytic cells at or near the deposition site, or can stimulate the secretion of fluids and cell-derived mediators that have secondary effects on the system.
Soluble materials deposited as, on, or within particles can diffuse into and through surface fluids and cells and be rapidly transported by the bloodstream throughout the body.
Furthermore, the ionic and lipid contents of surface fluids within the airways are complex and highly variable, and can lead to either enhanced solubility or to rapid precipitation of aqueous solutes.
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Furthermore, the clearance pathways and residence times for particles on airway surfaces are very different in the different functional parts of the respiratory tract.The mechanisms accounting for particle deposition in the lung airways during the inspiratory phase of a tidal breath are summarized in figure 10.2 .Particles larger than about 2 µm in aerodynamic diameter (diameter of a unit density sphere having the same terminal settling (Stokes) velocity) can have significant momentum and deposit by impaction at the relatively high velocities present in the larger airways.The revised ICRP Task Group's clearance model identifies the principal clearance pathways within the respiratory tract that are important in determining the retention of various radioactive materials, and thus the radiation doses received by respiratory tissues and other organs after translocation.The ICRP deposition model is used to estimate the amount of inhaled material that enters each clearance pathway.By contrast, airborne particles, with diffusion coefficients smaller by orders of magnitude than those for gases, tend to remain suspended in the tidal air, and can be exhaled without deposition.A significant fraction of the inhaled particles do deposit within the respiratory tract.In total, 90.4% of unrelated INH-resistant isolates could be identified by analysis of just two loci: kat G315 and the fab G1-inh A regulatory region.The respiratory system extends from the breathing zone just outside of the nose and mouth through the conductive airways in the head and thorax to the alveoli, where respiratory gas exchange takes place between the alveoli and the capillary blood flowing around them.Mutations in kat G, in particular the S315T substitution, are responsible for INH resistance in a large proportion of tuberculosis cases.However, the frequency of the kat G S315T substitution varies with population samples.