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INTRODUCTION

KEY POINTS

  • Skin participates directly in thermal, electrolyte, hormonal, metabolic, and immune regulation.

  • Percutaneous absorption depends on the xenobiotic’s hydrophobicity, which affects its ability to partition into epidermal lipid, and rate of diffusion through this barrier.

  • Cells of the epidermis and pilosebaceous units express biotransformation enzymes.

  • Irritant dermatitis is a nonimmune-related response caused by the direct action of a chemical on the skin.

  • Allergic contact dermatitis represents a delayed (type IV) hypersensitivity reaction, whereby minute quantities of material elicit overt reactions.

SKIN AS A BARRIER

A large (10% of body mass; 1.5-2 m2) and highly accessible organ, the skin protects the body against external insults, thus maintaining homeostasis. Physiologically, the skin participates directly in thermal, electrolyte, hormonal, metabolic, antimicrobial, and immune regulation. Rather than merely repelling noxious agents, the skin may react to them with various defensive mechanisms preventing widespread cutaneous and/or internal injuries. If an insult is severe or sufficiently intense to overwhelm the protective function of the skin, acute or chronic injury becomes manifest. The specific presentation depends upon a variety of intrinsic and extrinsic factors, including body site, duration of exposure, other environmental conditions, and the physicochemical properties of the insult (Table 19–1).

TABLE 19–1Factors Influencing Cutaneous Responses

Skin Histology

The skin consists of two major components, the outer epidermis and the underlying dermis, which are separated by a basement membrane (Fig. 19–1). The junction ordinarily is not flat, but undulating (rete ridges). In addition, epidermal appendages (hair follicles, sebaceous glands, and eccrine glands) span the epidermis and embed into the dermis. In thickness, the dermis comprises approximately 90% of the skin, and largely has a supportive function. A high content of collagen and elastin provide skin resilience and elasticity. Separating the dermis from underlying tissues is a layer of adipocytes, whose accumulation of lipids has a cushioning and thermoregulatory action. The blood supply to the epidermis originates in capillaries in the rete ridges at the dermoepidermal junction. Capillaries also supply ...

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