PRINCIPLES OF TOXICOLOGY - Biology East Borneo

9.2 MECHANISMS OF INDUSTRIALLY RELATED PULMONARY DISEASES 183is considered to be more compliant than type I, this might be the cause of the “stiffening” of the lungtissue, but this is not known for certain.EmphysemaWhenever inhaled toxins result in the progressive destruction of the alveolar walls of the lung tissue,there is an enlargement of the lung air spaces accompanied by a decrease in the surface area of thelung available for gas exchange. This is commonly referred to as emphysema, and it is a relativelycommon pulmonary disease condition in the United States. Although emphysema is due primarily totobacco smoke inhalation, a number of inhaled industrial toxins may also be responsible for thedevelopment of emphysematic conditions. For instance, the inhalation of coal dust by miners overextended periods has been shown to result in both pulmonary fibrosis and emphysema.Recent research has indicated that a genetically related deficiency in α-1-antiprotease, of abiochemical inhibitor of elastase, is clinically related to the relatively early onset of emphysema. It isbelieved that the breakdown of the alveolar walls is modulated by elastases, which are released byneutrophils and perhaps alveolar macrophages, and if the α-1-antiprotease enzyme is genetically absentor decreased, this results in a higher incidence of emphysema. In this scenario, if an inhaled toxincauses increased migration of the normally protective cells (neutrophils and macrophages) to the siteof the inhaled toxin deposition, then these cells may end up damaging the lung tissue in addition toeliminating the toxins.Pulmonary EdemaMany inhaled agents produce sufficient cellular toxicity to cause an increase in the membranepermeability of the alveocapillary membrane complex of the lung and other airway linings. This resultsin an increase in fluid, either in the interstitial space of the alveocapillary membrane complex or onthe surface of the airways or alveolar sacs. This increase in fluid is called edema, and its presenceimpedes the exchange of oxygen and carbon dioxide between the alveolar air and the pulmonary blood.If the decrease in gas exchange proceeds sufficiently, the affected individual can die, literally in theirown fluids.Among the many agents that result in pulmonary edema are the air pollutant gases, such as nitrogendioxide and ozone. These agents typically exert their lung toxicity at relatively low levels of exposurein air-pollution episodes, but in industrial exposures, workers may be exposed to considerably higherconcentrations. Chlorine and phosgene, two of the more potent inducers of pulmonary edema, wereshown to induce thousands of deaths when used as chemical warfare gases in World War I. Recently,it was reported that the Iraqi military has used one or both of these agents against the Kurdish minorityin that country. Since chlorine is now the primary chemical used to keep water supplies clean, itsindustrial use has soared. Municipalities use chlorine for their drinking water treatment; therefore, itsgeographic distribution is widespread. Large-scale releases of chlorine have occurred during transportto these disparate localities, and there have been a number of fatalities from pulmonary edemafollowing chlorine inhalation. Phosgene is also used frequently in industry; however, strict industrialhygiene controls, due to the extreme toxicity of the chemical, has resulted in a low frequency of workerinjury. Other agents known to cause pulmonary edema include nickel oxide, paraquat, cadmium oxide,and some industrial solvents.The delayed onset of pulmonary edema in most cases of chemical inhalation results in a significanthazard for exposed workers. Usually, the edema fluid is not readily detected by the exposed individualor by clinical examination for at least several hours after the termination of exposure.In a typical occupational exposure, the worker may experience short-term symptoms involvingirritation of the airway, which influences them to seek immediate medical assistance. Since theshort-term symptoms usually have no immediate cytotoxic sequelae, the medical examination willresult in no revelation of significant morbidity, and the patient will be released. Then, 4–24 h later, thepulmonary edema rapidly develops, usually while the patient is asleep. Often, when patients awake