LAYERS AND COMPONENTS OF THE SKIN

SKIN STRUCTURES

The skin is stratified horizontally into three compartments—the epidermis, dermis, and subcutaneous layer—and is penetrated vertically by appendages such as hair follicles, sweat glands, and sebaceous glands. The out-ermost, thinnest layer, the epidermis, forms a barrier to the world (the barrier function), keeping out water, bacteria, toxins, ultraviolet light, and allergens in healthy skin. The epidermis also shows the genetic expression of skin color and reveals dryness, softness, or roughness. It can be clear or diseased, as is the case with acne, or have precancerous or cancerous lesions, pigmenta-tion problems, psoriasis, rosacea, and a host of other conditions. Throughout the body, the epidermis is uniform in thickness, except for certain thickened areas, such as the palms and soles.

The dermis, composed of the papillary dermis and the thicker reticular dermis, lies below the epidermis. The papillary dermis contains thin, hap-hazardly arranged collagen fibers, abundant ground substance, and delicate elastic fibers, whereas the reticular dermis comprises thick collagen bundles and coarse elastic fibers. Upward projections of the dermis, the papillae, fit into the epidermal depressions, the rete ridges. This arrangement provides a greater interface between the epidermis and the dermis than would result from contact between two flat surfaces. A rich supply of blood vessels and nerve endings can be found in the dermis. The deepest layer of the skin, the subcutaneous layer, is composed primarily of fatty tissue.

THE EPIDERMIS

Keratinocytes and the Keratinocyte Maturation Cycle

Four cell types are found in the epidermis: keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Keratinocytes are the major cells of the epidermis. They originate at the basal layer, mature, lose their nucleus, and flat-ten as they move upward. At the uppermost level, they form a strong, flexible, dry surface known as the stratum corneum. This layer, composed of cells firmly attached to one another, continually loosens, detaches, and falls away in the nat-ural process of exfoliation that takes 30 to 40 days in normally maturing skin. However, this transit time varies widely after mild injury or major trauma, in the presence of disease states like psoriasis, and throughout the aging process.

Keratinocytes are involved in a steady state of cell production and cell loss. The keratinocyte maturation cycle is the amount of time it takes for a keratino-cyte to mature and transform into a corneocyte, reach the stratum corneum, and subsequently exfoliate from the surface of the epidermis. One of the main objectives of skin health, as discussed in this book, is restoration of a normal maturation cycle through skin conditioning. It usually takes 6 weeks of skin-conditioning treatment to complete one cycle, and more than one cycle may be required in some patients. Some of the factors that participate in the regulation of the keratinocyte maturation cycle are the dermis, hormones, vitamin A and its derivatives, epidermal growth factor, and cyclic nucleotides. Normal barrier function, in turn, increases skin tolerance. Skin barrier func-tion, however, can be disrupted by overuse of moisturizers. 

Melanocytes, Melanosomes, and Skin Pigmentation

Melanocytes are melanin-synthesizing cells that are found only in the basal layer where they are interspersed among the basal keratinocytes. Approximately every 10th cell of that single-cell layer is a melanocyte. Through its finger-like dendritic processes, each melanocyte is in contact with 30 to 40 keratinocytes. Inside the melanocyte, organelles known as melanosomes produce melanin pigment—the primary pigment of skin. These pigment granules migrate from the cytoplasm into the dendrites and are transferred from there into the sur-rounding keratinocytes, where they form a protective cap over the keratino-cyte nucleus, protecting the nuclear DNA from the effects of ultraviolet (UV) radiation. Normal pigmentation of the skin depends on the efficient transfer of melanosomes to keratinocytes.

Variation in normal skin color, including that due to racial differences or the process of tanning, is not determined by the number or density of melano-cytes but by the number, size, and distribution of melanosomes; the distribu-tion of the pigment granules in the melanosomes; and the quantity of melanin produced. Melanosomes in darkly pigmented skin are large, single, and indi-vidually bound by a membrane. In lightly pigmented skin, melanosomes are smaller and clustered together in complexes enclosed by a membrane.

The main function of melanin is to protect DNA from UV light by act-ing as an antioxidant to reduce inflammation. Even melanin production in dark skin leads to the desirable tan, whereas in fair skin it leads to freckles, uneven color tone, and no tanning. The two types of melanin are eumelanin and pheomelanin. Eumelanin is stable, darkens when oxidized by UV light (produces a tan), and protects from UV light at a sun protection factor of 4 to 8. It is dominant in dark skin (skin types IV to VI on the Fitzpatrick scale). Pheomelanin, on the other hand, is unstable, provides little natural UV pro-tection, and breaks down when exposed to UV light (causing DNA damage). Pheomelanin is present in all skin types (Fitzpatrick types I to VI) but is dom-inant in fair skin. It may be the causative factor in skin cancer in dark skin.

Melanin exists in the skin of animals and in many botanical and marine plants. Plant melanin should be included in skin care products, especially sun-screen, to offer extra protection from UV light, to protect skin melanocytes through an antioxidant effect, and to act as a shield to prevent penetration of UV light.

Tanning of the skin occurs in response to the UVA (320 to 380 nm) and UVB (290 to 320 nm) spectrums of solar radiation that reach the earth’s sur-face. Within a few minutes of exposure to UVA, an immediate reaction occurs that then fades over 6 to 8 hours. During this time, preexisting melanin is photo-oxidized, resulting in an immediate pigment darkening, and melano-cytes increase in size. A delayed reaction involving new pigment production becomes apparent only after 2 to 3 days of repeated exposure. This delayed reaction occurs in response to both UVA and UVB and involves an increase in the number of active melanocytes, enhanced melanosome production, and an increase in melanogenesis. The transfer of mature melanosomes from the melanocytes into keratinocytes increases, and keratinocyte proliferation increases. Changes also occur in the size and aggregation pattern of melano-somes, from smaller and grouped to larger and singly dispersed.

Skin can also darken in response to hormonal stimulation, such as with increased synthesis of melanocyte-stimulating hormone or adrenocorticotropic hormone, or during the poorly understood process of postinflammatory hyper-pigmentation. Persons with lentigines (sun-induced dark spots) show increased numbers of melanocytes at the dermal-epidermal junction. Lentigines tend to be stable in color regardless of the length of exposure to UV light. These lesions are believed to result from an increase in metabolically active melanocytes. Ephelides (freckles), on the other hand, are not due to an increase in mela-nocytes but represent areas of increased melanin synthesis. Freckles appear in childhood, and their pigmentation usually increases during the summer, indicating that melanocytes respond to UV light. Melasma, a very common patchy brown, tan, or blue-gray facial skin discoloration, is almost entirely seen in women in the reproductive years. It typically appears on the upper cheeks, upper lip, forehead, and chin. Melasma is thought to be the result of stimula-tion of melanocytes or pigment-producing cells by the female sex hormones estrogen and progesterone to produce more melanin pigments when the skin is exposed to sun. Women with a light brown skin type who are living in regions with intense sun exposure are particularly susceptible to developing this condi-tion. 

THE DERMIS

In contrast to the epidermis, the dermis is a layer of connective tissue 500 to 1,000 μm thick that is largely acellular. It is composed of a mucopolysac-charide gel held together by a fibrous matrix of primarily collagen fibers and about 5% elastin. The dermis lies beneath the epidermis and gives it struc-tural support. It also provides nutrition and removes waste products. The der-mis is subdivided into two layers: the more superficial papillary dermis and the deeper reticular dermis (see Figure 1.1). The papillary dermis is the most active dermal layer. It is constantly repairing damaged collagen and elastin tissue and producing collagen, elastin, and glycosaminoglycans. It contains a rich supply of blood vessels that penetrate from the deeper layers, as well as numerous nerve endings, thermoreceptors, and cryoreceptors.

Below the papillary dermis is the thicker, major layer of the dermis, the reticular dermis, which is densely packed with collagen and elastic fibers. Various cell types are also present, including mast cells, fibroblasts, macro-phages, and dermal dendritic cells. The transition from papillary dermis to upper reticular dermis (called the immediate reticular dermis, or IRD) can be observed histologically. The IRD is the line where collagen fibers become thicker and more horizontal and elastic fibers become less distinct. Peels reaching the papillary dermis and the IRD lead to maximum skin tighten-ing (Box 1.3). They are suitable for all skin types, and there is no risk for per-manent effects, such as hypopigmentation skin thinning or textural changes. Complications such as keloids are rare. Healing is rapid, usually occurring in 8 to 10 days. Procedures below the IRD, such as those penetrating to the upper reticular dermis, can achieve skin leveling, but they have a higher incidence of color and texture changes and the possibility of keloids.

Collagen and Tensile Strength

Collagen is produced by fibroblast cells that lie among collagen fibers and makes up approximately 70% of the dry weight of the dermis. It has great ten-sile strength—a single fiber 1 mm in diameter can withstand a load of up to 20 kg. It is insoluble because of chemically stabilizing intermolecular cross-linking. In young skin that has not been exposed to sun, mature colla-gen is cross-linked into collagen fibrils that come together into small groups of fibers, which are then organized into thin, wavy fiber bundles. The collagen fiber bundles are arranged in a mat-like orthogonal pattern, such that each layer is at right angles to the one above and the one below. These bundle for-mations are loosely arranged in the papillary dermis and become thicker in the deep dermis. Newly formed collagen fibrils become less soluble and more stable as they mature. Fully mature collagen fibers have a very low turnover rate compared with other body proteins.

In elderly persons, dermal collagen fibers become more heterogeneous, and the dermis becomes thinner. Reports on changes in the amount of collagen in unexposed human skin over time have been contradictory. It appears that the absolute amount of skin collagen decreases with age as skin becomes thinner, whereas the relative amount of collagen does not undergo significant change. Skin exposed to sunlight shows similar but more severe changes than nor-mally aged skin, with less insoluble collagen than normal skin.

Elastic Fibers, Skin Elasticity, and Resilience

Elastic fibers are extracellular matrix protein complexes produced by fibro-blasts, and they make up 2% to 4% of the total volume of the dermis. They form a network that is composed mostly of the protein elastin, which has unusual elasticity and tensile strength, and a small amount of microfibrils composed of a family of proteins. It is this network that maintains normal skin tension and provides extensibility. The integrity of the elastic fiber network in skin is very important because wrinkling, looseness, sagging, and other structural and mechanical changes in aging skin appear to be due to alterations in this net-work. In young skin, elastic fibers snap back quickly after stretching. Elastic fibers are continuously degraded and replaced by newly synthesized fibers in normal situations, but the turnover is slow.

Extracellular Matrix and Hydration

he insoluble fibers of collagen and elastin are imbedded in the gel-like extracel-lular matrix of the dermis. This matrix is made up of noncollagenous glycopro-teins and glycosaminoglycan-proteoglycan macromolecules. The glycoproteins facilitate cell adhesion, cell motility, and cell-matrix interactions, whereas the macromolecule complexes are important for hydration. Although the glycos-aminoglycans are less than 1% of the dry weight of the skin, they are able to bind up to 1,000 times their own weight in water. Hyaluronic acid and dermatan sul-fate are the major glycosaminoglycans in adult skin. As part of innate cutane-ous aging, the content of hyaluronic acid diminishes with age; this may in part explain the reduced turgor of aged skin. Because of their high water-binding capacity, glycosaminoglycans allow some movement in dermal structures.

Fibroblasts and the Synthesis and Degradation of Connective Tissue

Fibroblasts, the “master” cells of the dermis, are responsible for synthesizing the connective tissue elements (the dermal-extracellular matrix) of the dermis, including collagen, elastic fibers, and the proteoglycan-glycosaminoglycan macromolecules. They are more numerous and larger in the papillary dermis than in the reticular dermis. Fibroblasts also control the turnover of connec-tive tissue by secreting enzymes that degrade collagens (collagenases), elastin (elastases), and proteoglycans and glycosaminoglycans. With advancing age, fibroblasts become smaller and less active. In photodamaged skin, they are often hypertrophied.

Mast Cells and the Inflammatory Response

A second cell type of the dermis is the mast cell. These cells are found close to blood vessels, nerves, and appendages and are present in greater numbers in the subpapillary dermis. Mast cells are distinguished primarily by the presence of numerous, large cytoplasmic granules that contain histamine, enzymes, and other mediators. During an allergic reaction, mast cells bind to immunoglobulin E, and the granules discharge their contents as part of the inflammatory response.

THE SUBCUTANEOUS LAYER

The subcutaneous layer, composed of lobules of fatty tissue, functions as a buffer against blunt trauma and gives the skin its appealing full and plump appearance. It also provides “gliding ability” to both the dermis and epidermis, which helps to make skin more flexible. Areas with abundant sub-cutaneous tissue heal better and have less severe scarring than areas with a very thin or no subcutaneous layer. This can explain why certain areas of the face, such as the upper lip, jawline, and neck, where the dermis is in contact with the underlying muscles with little or no fat in between, have an increased tendency for fibrosis and scarring after procedures. It is very important to avoid deep dermal penetration in these areas.

SEBACEOUS GLANDS

Sebaceous glands are found on all parts of the body except the palms and soles, but they are small and relatively inactive in hairless areas. They are formed from epidermally derived cells that bud out from the side of a hair follicle. The purpose of the sebaceous glands is to form oil, sebum, which lubricates and thus protects the hair and skin. The dominant pathological condition of the sebaceous glands is acne.

There are several misconceptions about sebum and aging. Skin aging involves changes to collagen and elastin and does not depend on the amount of sebum production or skin dryness. Thus, oily skin does not age at a slower rate. Dryness is in fact related to the loss of glycosaminoglycans and abnormal barrier function (Box 1.7). Sebum helps to keep the skin at a slightly acidic pH (between 6 and 7).