Chapter 1: Structure and Functions of the Skin

The skin is the site of many complex and dynamic processes as demonstrated in Figure 1-1 and Table 1-1. These processes include barrier and immunologic functions, melanin production, vitamin D synthesis, sensation, temperature regulation, protection from trauma and aesthetics.

The epidermal barrier protects the skin from microbes, chemicals, physical trauma, and desiccation due to transepidermal water loss.^1–3 This barrier is created by differentiation of keratinocytes as they move from the basal cell layer to the stratum corneum. The keratinocytes of the epidermis are produced and renewed by stem cells in the basal layer resulting in replacement of the epidermis approximately every 28 days. It takes 14 days for these cells to reach the stratum corneum and another 14 days for the cells to desquamate.

Keratinocytes produce keratins, structural proteins that form filaments that are part of the keratinocyte cytoskeleton. In the stratum spinosum keratin filaments radiate outwards from the nucleus and connect with desmosomes which are prominent under the microscope giving a "spiny" appearance to cells. As cells move into the stratum granulosum, keratohyalin granules composed of keratin and profilaggrin are formed. Profilaggrin is converted into filaggrin (filament aggregation protein) that aggregates and aligns keratin filaments into tightly compressed parallel bundles that form the matrix for the cells of the stratum corneum. Filaggrin gene mutations are associated with ichthyosis vulgaris and atopic dermatitis. As keratinocytes move into the stratum corneum they lose their nuclei and organelles and develop a flat hexagon shape. These cells are stacked into a "bricks and mortar"–like pattern with 15 to 25 layers of cells (bricks) surrounded by lipids (mortar). The lipids consist of ceramides, free fatty acids, and cholesterol.

Epithelial cells at the interface between the skin and the environment provide the first line of defense via the innate immune system.^4–6 Epithelial cells are equipped to respond to the environment through a variety of structures including Toll-like receptors (TLRs) of which there are at least 10, nucleotide-binding oligomerization domain-like receptors, C-type lectins, and peptidoglycan recognition proteins. TLR-mediated activation of epithelial cells is also associated with the production of defensins and cathelicidins, families of antimicrobial peptides.

Dendritic cells bridge the gap between the innate and adaptive immune systems. Dermal dendritic cells can induce autoproliferation of T cells and production of cytokines as well as nitric oxide synthase. The exact function of dendritic epidermal Langerhans cells is an area of rapidly evolving research suggesting that these cells are very important to the modulation of the adaptive immune response.⁷

Melanocytes comprise 10% of the cells in the basal cell layer.⁸ There is another population of melanocytes in the hair follicle that is responsible for hair color and replacing epidermal melanocytes as needed (Figure 1-2). Melanocytes produce melanin, a pigmented polymer that absorbs UV light. Melanin is synthesized from tyrosine in several steps that require the enzyme tyrosinase. As melanin is produced it is then packaged into melanosomes, a specialized organelle. Melanosomes are phagocytosed by keratinocytes and moved to an area above the keratinocyte's nucleus acting as a protective shield from UV light. One melanocyte provides melanosomes for as many 30 to 40 keratinocytes. All humans have the same number of melanocytes. The variation in the degree of skin color is due to variations in melanosomes. Individuals with darker brown skin tones have more abundant, larger, and more dispersed melanosomes. Exposure to UV light stimulates the production of melanin within melanosomes producing a "tan." Tyrosinase deficiency is associated with albinism and vitiligo is associated with absence of melanocytes.

The main sources for vitamin D are dietary intake and production of vitamin D precursors by the skin. With exposure to UV light provitamin D₃ (7-dehydrocholesterol) in the epidermis is converted into previtamin D that converts into vitamin D₃. Vitamin D₃ is converted to its metabolically active form in the liver and kidneys.⁸

The skin is one of the principal sites of interaction with the environment and many types of stimuli are processed by the peripheral and central nervous systems.^9,10 Initially, cutaneous nerves were classified as being either "afferent" controlling sweat gland function and blood flow or "efferent" transmitting sensory signals to the central nervous system, but after the discovery of the neuropeptide substance P (SP) and other neuropeptides in sensory nerves, many trophic properties of nerve fibers and neuropeptides have been reported.

There are 3 major nerve types in the skin:

• Aβ fibers—large, heavily myelinated nerve fibers that transmit tactile sensation

• Aδ fibers—thinly myelinated nerve fibers involved in the transmission of short and fast painful stimuli

• C-fibers—unmyelinated nerves that transmit pain and itch sensations

Mixed nerve fiber bundles form a plexus from which individual nerve fibers extend toward their specific targets. The first tier is underneath the epidermis and innervates the epidermis and cutaneous mechanoreceptors or the upper dermis (Figure 1-3).

The second and third tiers are located between the dermis and subcutis or in the deep subcutis and innervate hair follicles, the arrector pili muscles, and sweat glands as well as the lower dermis and subcutis. All 3 plexi innervate blood vessels, smooth muscle cells, and mast cells, thereby connecting different skin cell populations with the brain.

The skin helps to regulate and maintain core body temperature through regulation of sweating and varying the blood flow in the skin. Evaporation of sweat contributes to temperature control of the body. Under normal conditions 900 mL of sweat is produced daily. With increased physical activity or increased environmental temperature, 1.4 to 3 L of sweat per hour can be produced.¹¹

The regulation of blood flow in the capillaries in the dermal papillae and other cutaneous vessels plays an important role in convective heat loss and heat conservation. Normally the blood flow in the skin is approximately 5% of the cardiac output, but in extremely cold temperatures it can drop to almost zero and in severe heat stress it can be as high as 60%.¹² Dysfunction of thermoregulation can lead to hyperthermia and hypothermia.

The dermis varies in thickness from 1 to 4 mm. It protects and cushions underlying structures from injury and provides support for blood vessels, nerves, and adnexal structures. It is separated from the epidermis by the basement membrane, which is created by the basal layer of the epidermis. Collagen is responsible for the tensile strength of the skin and comprises 75% of the dry weight of the dermis. Defects in collagen synthesis are associated with diseases such as Ehlers–Danlos syndrome (hyperextensible joints and skin). Elastic fibers are responsible for the elasticity and resilience of the skin and are 2% to 3% of the dry weight of the skin. Defects in elastic fibrils can be associated with cutis laxa and Marfan syndrome.

The perception of an individual's ethnicity, age, state of health, and attractiveness is affected by the appearance of his or her skin and hair. Sun-damaged skin, rashes, hair disorders, pigment disorders, and acne can have a profound effect on how individuals perceive themselves and others.