Structure and Function of Skin (2010)

SKIN STRUCTURE AND FUNCTION Introduction Skin is a highly vulnerable and visible organ that interfaces with the environment. The structural and functional relationships of the skin are complex. Therefore, the anatomical structure of skin is important so that an appreciable understanding of the barrier function, penetration, absorption, and immunological aspects of skin in response to chemicals, particles, or other insult can be well understood. Skin is an integrated, dynamic organ that has a myriad of biological functions that go far beyond its role as a barrier to the external environment (Table 1). It can serve as an environmental barrier by protecting the major internal organs, as a diffusion barrier that minimizes insensible water loss that could result in dehydration, and as a metabolic barrier that can metabolize a compound so that it may be excretable after absorption has occurred. The skin plays role in thermoregulation where blood vessels constrict to retain heat and dilate to dissipate heat. Hair in humans and the fur of lower mammals serve as insulation devices, while sweating facilitates heat loss by evaporation. Skin can serve as an immunological affector axis by having Langerhans cells in the epidermis to process antigens and also as an effector axis by establishing an inflammatory response when exposed to a foreign insult. It has a welldeveloped stroma that supports all of the other organs. Numerous receptors in skin can sense the modalities of touch, pain, and heat. Skin may also serve as an independent endocrine organ that synthesizes vitamin D by converting 7-dehydrocholesterol through two hydroxylations in the body to activate vitamin D. The first is in the liver that converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol, and the other occurs in the kidney and also in the skin and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D]. Skin is also a target for androgens, which regulate sebum production, and a target for insulin that regulates carbohydrate and lipid metabolism. The dermis of skin has sebaceous glands that can secrete sebum, which is a complex mixture of lipids that function as antibacterial agents or as a water-repellent shield in some animals. In addition, the skin contains both apocrine and eccrine sweat glands that produce a secretion, which contains scent that functions in territorial demarcation. The integument also plays a role in the biosynthesis of keratin, collagen, melanin, lipids, and carbohydrates, as well as in respiration and biotransformation of xenobiotics. The purpose of this chapter is to overview the anatomical structure and function of skin from a multifaceted perspective. In general, the basic architecture of the integument is similar in all mammals. However, differences may exist in the thickness of the epidermal layers (Table 2) and dermis in various regions of the body between species and within the same species. A thick stratum corneum can be found inglabrous skin areas such as the palmar and plantar surfaces where considerable abrasive action occurs. A thin epidermis can be found in areas where there is a heavy protective coat of hair or fur. Understanding these variations in the skin is extremely important in studies involving biopharmaceutics, dermatologicalformulations, cutaneous pharmacology, drug delivery, nanoparticle penetration, and dermatotoxicology.