The inflammatory reaction in chemical injury. 3. Leucocytosis and other histological changes induced by superficial injury.

Skin sites treated by the application of xylol, benzene, carbon tetrachloride, chloroform and 1/7-1/9 phenol were examined histologically after the application of these chemicals for ½-1 min. Degenerative changes in the first 5 min. progressed to necrosis of the cells of the epidermis and upper dermis in about 12 hr, the necrosis tissue later being undermined by regenerating epidermis. Within about 10 min. of applying the chemical irritants, the sub-epidermal capillary plexus became dilated and engorged with blood in parallel with the development of erythema. With mild irritation, this engorgement lessened in the 1st hr and became minimal in 2-8 hr, the latter period corresponding with the interval between the early and late phases of increased vascular permeability, when the sub-epidermal vessels were usually empty, though still dilated. With stronger irritation, the initial congestion was replaced by vascular stasis, but such lesions exhibited only a single strong phase of increased permeability. Stasis was sometimes associated with evidence of vascular damage. The small veins of the mid-dermis were initially congested. Between 3-8 hr, the sub-epidermal capillaries were usually dilated, but empty or in stasis; the mid-dermal veins contained increasing numbers of leucocytes which were mainly neutrophils, with less eosinophils and monocytes. Numerous neutrophils emigrated into the adjacent tissue when the lesions were 2-6 hr old. The intensity of the neutrophil response paralleled the amount of epidermal necrosis, the white cells being noticeably confined to the dermis overlain by necrotic epidermis or to the necrotic epidermis itself. During the late phase of increased permeability induced by mild irritants, the dermal vessels again became filled with blood, but the number of neutrophils in the perivascular tissues was declining before the onset of the late phase of increased permeability. Organoid arterio-venous anastomoses in the panniculus adiposus exhibited no changes. Guinea-pig skin normally contained varying numbers of eosinophils, in parallel with the number in the peripheral blood. In chemical injury, eosinophils accumulated and emigrated in step with the neutrophils, remained further removed from the necrotic epidermis, and appeared to survive longer than the neutrophils. Monocytes accumulated in blood vessels at the same time as neutrophils, but were not “labelled” and therefore not counted after migration into the injured tissues. After chemical injury and prior to the late permeability response, injected histamine rapidly increased permeability, presumably of the engorged vessels in the lower dermis and panniculus adiposus; re-application at this stage of a chemical irritant evoked no permeability response. The results strongly suggest that the phasic nature of erythema and increased vascular permeability is determined by diversion of blood flow from the vessels of the upper dermis to vessels of the deep dermis, panniculus adiposus and panniculus carnosus.