The skin is the largest and among the most complex organs of the body. Although the skin functions simply as a protective barrier to interface with our environment, its structure and physiology are complex. The skin protects against most noxious agents, such as chemicals (by the impermeability of the epidermis), solar radiation (by means of pigmentation), infectious agents (through efficient immunosurveillance), and physically deforming forces (by the durability of the dermis). Its efficient ability to conserve or disperse heat makes the skin the major organ responsible for thermoregulation. To direct all these functions, the skin has a highly specialized nervous structure. The palms and soles are particularly thick to bear weight. The fingertips have the highest density of sensory innervation and allow for intricate tasks. Even the lines of the skin, first described by Langer, are oriented perpendicularly to the long axis of muscles to allow the greatest degree of stretching and contraction without deformity.


The skin is divided into three layers: the epidermis, the basement membrane, and the dermis. The epidermis is composed mainly of cells (keratinocytes), with very little extracellular matrix. The deep, mitotically active, basal cells are a single-cell layer of the least-differentiated keratinocytes. Some multiplying cells leave the basal layer and begin to travel upward. In the spinous layer, they lose the ability to undergo mitosis. These differentiated cells start to accumulate keratohyalin granules in the granular layer. Finally, in the horny layer, the keratinocytes age, the once-numerous intercellular connections disappear, and the dead cells are shed. The keratinocyte transit time is between 40 and 56 days. The internal skeleton of cells (intermediate filaments), called keratins in epithelial cells, play an important role in the function of the epidermis. Intermediate filaments provide flexible scaffolding that enables the cell to resist external stress. Different keratins are expressed at different stages of keratinocyte maturation. In the mitotically active inner layer of the epidermis, the keratinocytes mainly express keratins 5 and 14. Patients with epidermolysis bullosa simplex, a blistering disease, were found to have a point mutation in one or the other keratin gene, thus revealing the etiology of one of the more baffling skin diseases. Melanocytes migrate to the epidermis from precursor cells in the neural crest and provide a barrier to radiation. There are 35 keratinocytes for every melanocyte. The melanocytes produce the pigment melanin from tyrosine and cysteine. The pigment is packaged in melanosomes and transported to the tips of dendritic processes and phagocytized by the keratinocyte (apocopation), thus transferring the pigment to the keratinocyte. The melanin aggregates on the superficial side of the nucleus in an umbrella shape. The density of melanocytes is constant among individuals of different skin color. The rate of melanin production, transfer to keratinocytes, and melanosome degradation determine

the degree of skin pigmentation. Genetically activated factors, as well as ultraviolet radiation, hormones such as estrogen, adrenocorticotropic hormone, and melanocyte-stimulating hormone, influence these activities. The Langerhans cells migrate from the bone marrow and function as the skin’s macrophages.

The Langerhans cells constitutively express class II major histocompatibility antigens and have antigen-presenting capabilities. These cells play a crucial role in immunosurveillance against viral infections and neoplasms of the skin, and may initiate skin allograft rejection. The dermis is mostly comprised of several structural proteins. Collagen constitutes 70 percent of the dry weight of dermis and is responsible for its remarkable tensile strength. Of the seven structurally distinct collagens, the skin contains mostly type I. Early fetal dermis contains mostly type III (reticulin fibers) collagen, but this remains only in the basement membrane zone and the perivascular regions in postnatal skin. Elastic fibers are highly branching proteins that are capable of being reversibly stretched to twice their resting length. This allows skin to return to its original form after stretching. Ground substance, consisting of various polysaccharide–polypeptide (glycosaminoglycans) complexes, is an amorphous material that fills the remaining spaces.

Fibroblasts are scattered throughout the dermis and are responsible for production and maintenance of the protein matrix. Recently, proteins that control the proliferation and migration of fibroblasts have been isolated. The study of fibroblast activity by these growth factor interactions is crucial to understanding wound healing and organogenesis.

The basement membrane zone of the dermoepidermal junction is a highly organized structure of proteins that anchors the epidermis to the dermis. Mechanical disruption or a genetic defect in the synthesis of this structure results in separation of the epidermis from the dermis.

The remaining structures of the skin are situated in the dermis. An intricate network of blood vessels regulates body temperature. Vertical vascular channels interconnect two horizontal plexuses, one at the dermal–subcutaneous junction and one in the papillary dermis. Glomus bodies are tortuous arteriovenous shunts that allow a tremendous increase in blood flow to the skin when open. This ability not only provides for the nutritional needs of the skin, but enables it to dissipate a vast amount of body heat when needed. Sensory innervation follows a dermatomal distribution from segments of the spinal cord. These fibers connect to corpuscular receptors (pacinian, Meissner, and Ruffini) that respond to pressure, vibration, and touch, and to “unspecialized” free nerve endings associated with Merkel cells of the basal epidermis, and to hair follicles. These nerves are stimulated by temperature, touch, pain, and itch. The skin has three main adnexal structures. The eccrine glands, which produce sweat, are located over the entire body but are concentrated on the palms, soles, axillae, and forehead. The apocrine glands are found primarily in the axillae and the anogenital region. In lower mammals, these glands produce scent hormones (pheromones).