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

Vesicantstions with margination, dilatations of the nuclearenvelope, mitochondrial swelling, and tonofilamentcondensations. 75 These early basal cytopathologicchanges were confirmed by immunohistochemistryto be associated with an HD-induced apoptosis. Thisfinding suggests that HD-induced cell death involvesearly apoptosis and late necrosis, which temporarilyoverlap to produce a basal cell death pathway alongan apoptotic-necrotic continuum (Figure 8-10). 82During vesication, in vivo models generate characabcdFig 8-9. Light microscopic (a, b) and electron microscopic (c, d) presentations of hairless guinea pig skin exposed to sulfurmustard vapor reveal that the epithelial basal cell of the stratum germinativum is selectively affected to the exclusion ofother epidermal cells. Following an apparent latency period of 4 to 6 hours, the basal cell pathology progresses to includeextensive hydropic vacuolation, swollen endoplasmic reticulum, dilated mitochondria, coagulation of monofilaments,nuclear pyknosis, and cell death. At 12 to 24 hours, microvesicles/microblisters form at the dermal-epidermal junction,which cleave the epidermis from the dermis. The cavity formed within the lamina lucida of the basement membrane as aconsequence of basal cell pathology, and perhaps as the result of disabling of basement membrane attachment proteins, isinfiltrated with cellular debris, inflammatory cells, fibers, and tissue fluid. (a) Unexposed perilesional skin site serves ascontrol, showing epidermis (ep), dermis (d), basement membrane (arrows), basal cells of the stratum germinativum (bc).(b) Affected skin 9 hours after exposure to HD vapor, showing degenerating basal cells with karyorrhectic and pyknoticnuclei (pyk). (c) Affected skin 12 hours after HD exposure, showing microvesicles (mv) forming at the basement membranezone in association with the microenvironment of degenerating basal cells. (d) Affected skin 24 hours after HD exposure,showing microvesicles that have coalesced to form a characteristic microblister (mb) that separates the epidermis from thedermis. Original magnification × 220.Photographs: Courtesy of John P Petrali, PhD, US Army Medical Research Institute of Chemical Defense, and Stephanie RFroberg, Graphics Department, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Md.and isolated perfused porcine skin flaps. 74–80Ultrastructural pathology. Ultrastructural studiesof in vivo models have expanded mustard investigationsto elaborate important effects on subcellularentities of the basal cell and the basement membranemicroenvironment. 73,74,81 During prevesication, modelsconsistently present subcellular nuclear injury tobasal cells to the exclusion of cells of other epidermalstrata. These injuries, typically presenting at 6 hourspostexposure, include nuclear chromatin condensa-271