Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Aspects of Chemical Warfareof toxic gas inhalation can easily be assessed by measuringbasic pulmonary function. Several irritantssuch as phosgene, chlorine, and PFIB initiate reactionsthat result in problems with physiological breathingprocesses. Cranial nerve input in the nasopharyngealregion is mainly responsible for initiating changes inrespiratory function, as evidenced by altered breathingmechanics. Experiments in mice exposed to phosgeneshow that minute ventilation is increased followingexposure, 37 caused by an increase in respiratory ratein response to local irritation from the gas. Inspiratoryand expiratory flow rates are also compromised bylocal sensory irritation because of formation of hydrochloricacid in the mucous membranes in the upperairway of the central airway compartment. Severalstudies found decreased dynamic compliance andincreases in both airway resistance and tracheal pressureto be predictable patterns of response followingirritant gas exposure. 38–41 Phosgene exerts much of itstoxic effect in the peripheral compartment of the lung,and histopathologic specimens show a significant alterationof the acinar type I and II epithelial cell layersof the air–blood barrier. Exposure causes significantpulmonary edema and respiratory acidosis throughincreased Pc o 2saturation, decreased Pao 2saturation,and decreased arterial pH. 42–44 Similar responses havebeen observed in animal models using chlorine, PFIB,and ammonia. Studies involving PFIB have demonstratedthat rats made to exercise following exposureexhibited an enhancement of transcellular transport ofblood proteins to the alveolar surface. 45,46 These datasuggest that although the lung may be injured andedematous, fleeing from the site of exposure may notin itself contribute to the edematous effect.Decreased body weight is a useful indicator ofexposure and systemic toxicity. Pulmonary edemaformation can be estimated by the lung wet weightto dry weight ratio, which increases over time as theinjury progresses . Although the wet/dry weight ratiois an important measure of edema, it may not showsubtle effects that preexist fulminant alveolar edema.A valuable indicator of what is actually occurring inthe deep lung environment is bronchoalveolar lavagefluid (BALF). BALF tests provide a wealth of information.Lavage fluid protein levels give a good indicationof subtle changes in the integrity of the air–bloodbarrier. Increased protein levels can be measured insome cases hours prior to gross alveolar edema formation.This may indicate that interstitial edema isoccurring. Much use has been made of the electrolytehomeostatic responses to toxic gas exposure. Sciuto etal have shown that phosgene exposure can producea possibly deleterious effect on lung homeostaticprocess by altering ionized Ca ++ , Na + , and K + levelsindirectly, thus indicating possible compromisedNa + , K + , or Ca ++ -adenosine triphosphatase pumpfunction. 47 Inhalation of irritants such as phosgene isknown to eventually result in immunosuppression,which may increase mortality via infection in thecompromised lung. 48,49Genomic studies have provided insight into the effectsof toxic gas exposure on gene expression levels. Inphosgene-exposed mice, it was demonstrated that theearliest changes (occurring within 1 to 4 hours) in lungtissue involved increased expression levels of antioxidantenzymes of the glutathione redox cycle. 50 Thesedata strongly suggest that free-radical–mediated injuryprocesses are active well before gross pathophysiologicchanges become manifest. It has been shown that invitro exposure of epithelial cells to nitrogen dioxidecan cause a range of problems in the entire length ofthe respiratory tract. Many of these detrimental effectsare the result of activated reactive nitrogen speciesfree radicals such as the peroxy radical OONO - or thenitrogen dioxide radical •NO 2itself. 51Riot control agents, also called incapacitants, cancause ocular and cutaneous as well as acute pulmonaryresponses during exposure. Although generallynonlethal, incapacitants may have magnified contactproblems if exposure occurs within a confined space.Symptoms resulting from a single exposure can lastfor years. 8Pathophysiological Effects of ExposureExamination of histopathological effects on chemicallyexposed lung tissue provides critical informationon the effects of a C × T response. The mechanisms oflung injury and repair are summarized in Figure 10-2. 52 Evaluation of phosgene-induced pulmonary injuryto the peripheral compartment revealed characteristictemporal acute toxicity lesions. Early lesions of atoxic gas exposure can be characterized by leakage ofedema, fibrin, and erythrocytes from the pulmonarymicrovasculature into the alveolar spaces and interstitialtissues. In general, alveolar and interstitial edemacan characterize the earliest and most significant pulmonarychanges. Epithelial damage in the terminalbronchioles and alveoli as well as mild inflammatorycell infiltrates can accompany increasing pulmonaryedema. The repair and regeneration of epithelialdamage centered on the terminal bronchioles maycomplement the resolution of edema. 53 In this studyearly indicators of phosgene-induced pulmonary injurywere identified by comparing acute pulmonaryhistopathologic changes to bronchoalveolar lavage andlung wet-weight gravimetric measurements. Of theBALF parameters studied, lactate dehydrogenase and348