Epidermis

The mature epidermis is a stratified epithelial tissue composed predominantly of keratinocytes. The function of the epidermis is protection of the organism from the external environment and the prevention of water loss. The process of epidermal differentiation results in the formation of a functional barrier to the external world. Keratinocytes are composed largely of keratin filaments. These proteins are members of the family of intermediate filaments. The predominant keratins expressed within the keratinocytes change with cellular differentiation. The epidermis comprises four histologically recognizable layers. The first or basal layer consists of columnar cells that rest on the dermal-epidermal junction. Basal keratinocytes are connected to the dermal-epidermal junction by hemidesmosomes. Basal keratinocytes are attached to themselves and to the cells in the spinous layer by desmosomal, tight, gap, and adherens junctions. The role of the basal keratinocyte is to serve as a continuing supply of keratinocytes for the normally differentiating epidermis as well as a reservoir of cells to repair epidermal damage. The second layer consists of 3 to 4 rows of spinous cells. Their role is to begin formation of the epidermal barrier and to initiate vitamin D synthesis. The third layer consists of 2 to 3 rows of granular appearing cells. Granular cells continue the process of epidermal barrier formation and prepare for the formation of the fourth layer or stratum corneum, which is composed of multiple layers of dead, highly compacted cells. The dead cells are composed mainly of disulfide-bonded keratins cross-linked by filaggrins. The intercellular spaces are composed of hydrophobic lipids, predominantly ceramides. As the stratum corneum is replenished, the old stratum corneum is shed in a highly regulated process. The normal process of epidermal differentiation from basal cell to shedding of stratum corneum takes 28 days.

The epidermis also contains 3 other cell types. The melanocytes are pigment-forming cells, which are responsible for skin color and protection from ultraviolet radiation. Epidermal melanocytes are derived from the neural crest and migrate to the skin during embryonic life. They reside in the interfollicular epidermis and in the hair follicles and increase in number in the epidermis by mitosis or migration of additional cells into the epidermis. Melanocytes produce intracellular organelles (melanosomes) containing melanin. There is approximately 1 melanocyte per 36 keratinocytes in the epidermal melanin unit. The melanosomes are then transferred via melanocyte dendrites to the keratinocytes. Merkel cells are type I slow-adapting mechanosensory receptors for touch. Langerhans cells are dendritic cells of the mononuclear phagocyte system. They are recognized electron microscopically by a specific organelle, the Birbeck granule. These cells are derived from bone marrow and participate in immune reactions in the skin, playing an active part in antigen presentation and processing.

The junction of the epidermis and dermis is the basement membrane zone. This complex structure is a result of contributions from both epidermal and mesenchymal cells. The dermal-epidermal junction extends from the basal cell plasma membrane to the uppermost region of the dermis. Ultrastructurally, the basement membrane appears as a trilaminar structure, consisting of a lamina lucida immediately adjacent to the basal cell plasma membrane, a central lamina densa, and the subbasal lamina on the dermal side of the lamina densa. Several structures within this zone act to anchor the epidermis to the dermis. The plasma membrane of basal cells contains electron-dense plates known as hemidesmosomes; tonofilaments course within basal cells to insert at these sites. The hemidesmosomes are composed of 180- and 230-kd bullous pemphigoid antigens, α6β4 and α3β1 integrins, and plectin. Anchoring filaments originate in the plasma membrane, primarily near the hemidesmosomes, and insert into the lamina densa. Anchoring fibrils, composed predominantly of type VII collagen, extend from the lamina densa into the uppermost dermis, where they insert into anchoring plaques.

Dermis

The dermis provides the skin with most of its mechanical properties. The dermis forms a tough, pliable, fibrous supporting structure between the epidermis and the subcutaneous fat. It consists of collagen and elastic and reticulin fibers embedded in an amorphous ground substance; it contains blood vessels, lymphatics, mast cells, neural structures, eccrine and apocrine sweat glands, hair follicles, sebaceous glands, and smooth muscle. Morphologically, the dermis can be divided into 2 layers: the superficial papillary layer that interdigitates with the rete ridges of the epidermis and the deeper reticular layer that lies beneath the papillary dermis. The papillary layer is less dense and more cellular, whereas the reticular layer appears more compact because of the coarse network of interlaced collagen and elastic fibers.

The predominant dermal cell is a spindle-shaped fibroblast that is responsible for the synthesis of collagen, elastic fibers, and mucopolysaccharides. Phagocytic histiocytes, mast cells, and motile leukocytes are also present. The gelatinous ground substance serves as a supporting medium for the fibrillar and cellular components and as a storage place for a substantial portion of body water. Nutrients are supplied to both epidermis and dermis by the dermal blood vessels.

Subcutaneous Tissue

Panniculus, or subcutaneous tissue, consists of fat cells and fibrous septa that divide it into lobules and anchor it to the underlying fascia and periosteum. Blood vessels and nerves are also present in this layer, which serves as a storage depot for lipid, an insulator to conserve body heat, and a protective cushion against trauma.

Appendageal Structures

Appendageal structures are derived from aggregates of epidermal cells that become specialized during early embryonic development. Small buds (primary epithelial germs) appear in the 3rd fetal month and give rise to hair follicles, sebaceous and apocrine glands, and the attachment bulges for the arrector pili muscles. Eccrine sweat glands are derived from separate epidermal downgrowths that arise in the 2nd fetal month and are completely formed by the 5th month. Formation of nails is initiated in the 3rd intrauterine month.

Hair Follicles

The hair follicle is the most prominent structure in the pilary complex, which includes the sebaceous gland, the arrector pili muscle, and, in areas such as the axillae, an apocrine gland. Hair follicles are distributed throughout the skin, except in the palms, soles, lips, and glans penis; if destroyed, they cannot regenerate. Individual follicles extend from the surface of the epidermis to the deep dermis. The hair follicle is divided into four segments: the infundibulum, which extends from the skin surface to the opening of the sebaceous duct; the isthmus, extending from the sebaceous duct opening to the bulge; the lower follicle between the bulge and the hair bulb; and the hair bulb. The bulge is at the insertion of the arrector pili muscle. The bulge is the site of the skin stem cells. The differentiation fate of these stem cells is in part controlled by c-myc. The bulb is where the matrix cells and the dermal papilla are involved in formation and maintenance of the hair. The activins and their receptors and binding proteins are important regulators of cell proliferation, differentiation, and apoptosis in hair follicle initiation and hair cycling. The growing hair consists of the hair shaft and its supporting sheaths.

Human hair growth is cyclic, with alternate periods of growth (anagen) and rest (telogen). The length of the anagen phase varies from months to years. At birth, all hairs are in the anagen phase. Subsequent generative activity lacks synchrony, so that an overall random pattern of growth and shedding prevails. At any time, ≈85% of hairs are in the anagen phase. Scalp hair usually grows about 1 cm/mo.

The types of hair are fetal lanugo, terminal, and vellus. Lanugo hair is thin and short; this hair is shed before term and is replaced by vellus hair by 36-40 wk of gestation. Vellus hair is short, soft, and frequently unpigmented and is distributed over the rest of the body. Terminal hair is long and coarse and is found on the scalp, beard, eyebrows, eyelashes, and axillary and pubic areas. During puberty, androgenic hormone stimulation causes pubic, axillary, and beard hair to change from vellus hair to terminal hair.

Sebaceous Glands

Sebaceous glands occur in all areas except the palms and soles and dorsa of the feet, but they are most numerous on the face, upper chest, and back. Their ducts open into the hair follicles except on the lips, prepuce, and labia minora, where they emerge directly onto the mucosal surface. These holocrine glands are saccular structures that are often branched and lobulated and consist of a proliferative basal layer of small flat cells peripheral to the central mass of lipidized cells. The latter cells disintegrate as they move toward the duct and form the lipid secretion known as sebum, which consists of cellular debris, triglycerides, phospholipids, and cholesterol esters. Sebaceous glands depend on hormonal stimulation and are activated by androgens at puberty. Fetal sebaceous glands are stimulated by maternal androgens, and their lipid secretion, together with desquamated stratum corneum cells, constitutes the vernix caseosa.

Apocrine Glands

The apocrine glands are located in the axillae, areolae, perianal and genital areas, and the periumbilical region. These large, coiled, tubular structures continuously secrete an odorless milky fluid that is discharged in response to adrenergic stimuli, usually as a result of emotional stress. Bacterial decomposition of apocrine sweat accounts for the unpleasant odor associated with perspiration. Apocrine glands remain dormant until puberty, when they enlarge and secretion begins in response to androgenic activity. The secretory coil of the gland consists of a single layer of cells enclosed by a layer of contractile myoepithelial cells. The duct is lined with a double layer of cuboidal cells and opens into the pilosebaceous complex. Although apocrine glands do not function in thermoregulation, they are involved in certain disease processes.

Eccrine Sweat Glands

Eccrine sweat glands are distributed over the entire body surface, including the palms and soles, where they are most abundant. Those on the hairy skin respond to thermal stimuli and serve to regulate body temperature by delivering water to the skin surface for evaporation; in contrast, sweat glands on the palms and soles respond mainly to psychophysiologic stimuli.

Each eccrine gland consists of a secretory coil located in the reticular dermis or subcutaneous fat and a secretory duct that opens onto the skin surface. Sweat pores can be identified on the epidermal ridges of the palm and fingers with a magnifying lens but are not readily visualized elsewhere. Two types of cells constitute the single-layered secretory coil: small dark cells and large clear cells. These rest on a layer of contractile myoepithelial cells and a basement membrane. The glands are supplied by sympathetic nerve fibers, but the pharmacologic mediator of sweating is acetylcholine rather than epinephrine. Sweat from these glands consists of water, sodium, potassium, calcium, chloride, phosphorus, lactate, and small quantities of iron, glucose, and protein. The composition varies with the rate of sweating but is always hypotonic in normal children.

Nails

Nails are specialized protective epidermal structures that form convex, translucent, tight-fitting plates on the distal dorsal surfaces of the fingers and toes. The nail plate, which is derived from a metabolically active matrix of multiplying cells situated beneath the posterior nail fold, grows forward at a rate of ≈1 cm every 3 months. The nail plate is bounded by the lateral and posterior nail folds; a thin eponychium (the cuticle) protrudes from the posterior fold over a crescent-shaped white area called the lunula. The pink color reflects the underlying vascular bed.