The skin covers the entire external surface of the human body and is the principal site of interaction with the surrounding world. It serves as a protective barrier that prevents internal tissues from exposure to trauma, ultraviolet (UV) radiation, temperature extremes, toxins, and bacteria. Other important functions include sensory perception, immunologic surveillance, thermoregulation, and control of insensible fluid loss.
The integument consists of 2 mutually dependent layers, the epidermis and dermis, which rest on a fatty subcutaneous layer, the panniculus adiposus. (See the image below.) The epidermis is derived primarily from surface ectoderm but is colonized by pigment-containing melanocytes of neural crest origin, antigen-processing Langerhans cells of bone marrow origin, and pressure-sensing Merkel cells of neural crest origin. The dermis is derived primarily from mesoderm and contains collagen, elastic fibers, blood vessels, sensory structures, and fibroblasts. 
During the fourth week of embryologic development, the single cell thick ectoderm and underlying mesoderm begin to proliferate and differentiate. The specialized structures formed by the skin, including teeth, hair, hair follicles, fingernails, toenails, sebaceous glands, sweat glands, apocrine glands, and mammary glands also begin to appear during this period in development. Teeth, hair, and hair follicles are formed by the epidermis and dermis in concert, while fingernails and toenails are formed by the epidermis alone. Hair follicles, sebaceous glands, sweat glands, apocrine glands, and mammary glands are considered epidermal glands or epidermal appendages, because they develop as downgrowths or diverticula of the epidermis into the dermis. [1, 2]
The definitive multi-layered skin is present at birth, but skin is a dynamic organ that undergoes continuous changes throughout life as outer layers are shed and replaced by inner layers. Skin also varies in thickness among anatomic location, sex, and age of the individual. This varying thickness primarily represents a difference in dermal thickness, as epidermal thickness is rather constant throughout life and from one anatomic location to another. Skin is thickest on the palms and soles of the feet (1.5 mm thick), while the thinnest skin is found on the eyelids and in the postauricular region (0.05 mm thick).
Male skin is characteristically thicker than female skin in all anatomic locations. Children have relatively thin skin, which progressively thickens until the fourth or fifth decade of life when it begins to thin. This thinning is also primarily a dermal change, with loss of elastic fibers, epithelial appendages, and ground substance. 
The epidermis contains no blood vessels and is entirely dependent on the underlying dermis for nutrient delivery and waste disposal via diffusion through the dermoepidermal junction. The epidermis is a stratified, squamous epithelium that consists primarily of keratinocytes in progressive stages of differentiation from deeper to more superficial layers. The named layers of the epidermis include the stratum germinativum, stratum spinosum, stratum granulosum, and stratum corneum.
The stratum germinativum, or the basal layer, is immediately superficial to the dermoepidermal junction. This single cell layer of keratinocytes is attached to the basement membrane via hemidesmosomes.
As keratinocytes divide and differentiate, they move from this deeper layer to the more superficial layers. Once they reach the stratum corneum, they are fully differentiated keratinocytes devoid of nuclei and are subsequently shed in the process of epidermal turnover. Cells of the stratum corneum are the largest and most abundant of the epidermis. This layer ranges in thickness from 15-100 or more cells depending on anatomic location and is the primary protective barrier from the external environment.
Melanocytes, derived from neural crest cells, primarily function to produce a pigment, melanin, which absorbs radiant energy from the sun and protects the skin from the harmful effects of UV radiation. Melanin accumulates in organelles termed melanosomes that are incorporated into dendrites anchoring the melanosome to the surrounding keratinocytes. Ultimately, the melanosomes are transferred via phagocytosis to the adjacent keratinocytes where they remain as granules. Melanocytes are found in the basal layer of the epidermis as well as in hair follicles, the retina, uveal tract, and leptomeninges. These cells are the sites of origin of melanoma.
In areas exposed to the sun, the ratio of melanocytes to keratinocytes is approximately 1:4. In areas not exposed to solar radiation, the ratio may be as small as 1:30. Absolute numbers of melanosomes are the same among the sexes and various races. Differing pigmentation among individuals is related to melanosome size rather than cell number. Sun exposure, melanocyte-stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), estrogens, and progesterones stimulate melanin production. With aging, a decline is observed in the number of melanocytes populating the skin of an individual. Since these cells are of neural crest origin, they have no ability to reproduce.
Langerhans cells originate from the bone marrow and are found in the basal, spinous, and granular layers of the epidermis. They serve as antigen-presenting cells. They are capable of ingesting foreign antigens, processing them into small peptide fragments, binding them with major histocompatibility complexes, and subsequently presenting them to lymphocytes for activation of the immune system. An example of activation of this component of the immune system is contact hypersensitivity.
Merkel cells, also derived from neural crest cells, are found on the volar aspect of digits, in nail beds, on the genitalia, and in other areas of the skin. These cells are specialized in the perception of light touch. [1, 3]
The primary function of the dermis is to sustain and support the epidermis. The dermis is a more complex structure and is composed of 2 layers, the more superficial papillary dermis and the deeper reticular dermis. The papillary dermis is thinner, consisting of loose connective tissue containing capillaries, elastic fibers, reticular fibers, and some collagen. The reticular dermis consists of a thicker layer of dense connective tissue containing larger blood vessels, closely interlaced elastic fibers, and coarse bundles of collagen fibers arranged in layers parallel to the surface.
The reticular layer also contains fibroblasts, mast cells, nerve endings, lymphatics, and epidermal appendages. Surrounding the components of the dermis is the gel-like ground substance, composed of mucopolysaccharides (primarily hyaluronic acid), chondroitin sulfates, and glycoproteins. The deep surface of the dermis is highly irregular and borders the subcutaneous layer, the panniculus adiposus, which additionally cushions the skin.
The fibroblast is the major cell type of the dermis. These cells produce and secrete procollagen and elastic fibers. Procollagen is terminally cleaved by proteolytic enzymes into collagen that aggregates and becomes cross-linked. These tightly cross-linked collagen fibers provide tensile strength and resistance to shear and other mechanical forces. Collagen makes up 70% of the weight of the dermis, primarily Type I (85% of the total collagen) and Type III (15% of the total collagen). Elastic fibers constitute less than 1% of the weight of the dermis, but they play an enormous functional role by resisting deformational forces and returning the skin to its resting shape. 
The dermoepidermal junction is an undulating basement membrane that adheres the epidermis to the dermis. It is composed of 2 layers, the lamina lucida and lamina densa. The lamina lucida is thinner and lies directly beneath the basal layer of epidermal keratinocytes. The thicker lamina densa is in direct contact with the underlying dermis. These structures are the target of immunologic injury in bullous pemphigoid and epidermolysis bullosa.
Dermal papillae from the papillary dermis contain a plexus of capillaries and lymphatics oriented perpendicular to the skin surface. These fingerlike projections are surrounded by similar projections of the epidermis. This highly irregular junction greatly increases the surface area over which oxygen, nutrients, and waste products are exchanged between the dermis and the avascular epidermis. 
Epidermal appendages are intradermal epithelial structures lined with epithelial cells with the potential for division and differentiation. These are important as a source of epithelial cells, which accomplish reepithelialization should the overlying epidermis be removed or destroyed in situations such as partial thickness burns, abrasions, or split-thickness skin graft harvesting.
Epidermal appendages include the following:
They often are found deep within the dermis and in the face may even lie in the subcutaneous fat beneath the dermis. This accounts for the remarkable ability of the face to reepithelialize even the deepest cutaneous wounds. 
Sebaceous glands, or holocrine glands, are found over the entire surface of the body except the palms, soles, and dorsum of the feet. They are largest and most concentrated in the face and scalp where they are the sites of origin of acne. The normal function of sebaceous glands is to produce and secrete sebum, a group of complex oils that include triglycerides and fatty acid breakdown products, wax esters, squalene, cholesterol esters, and cholesterol. Sebum lubricates the skin to protect it against friction and makes the skin more impervious to moisture.
Sweat glands, or eccrine glands, are found over the entire surface of the body except the vermillion border of the lips, the external ear canal, the nail beds, the labia minora, and the glans penis and the inner aspect of the prepuce. They are most concentrated in the palms and soles and the axillae.
Each gland consists of a coiled secretory intradermal portion that connects to the epidermis via a relatively straight distal duct. The normal function of the sweat gland is to produce sweat, which cools the body by evaporation. The thermoregulatory center in the hypothalamus controls sweat gland activity through sympathetic nerve fibers that innervate the sweat glands. Sweat excretion is triggered when core body temperature reaches or exceeds a set point.
Apocrine and mammary glands
Apocrine glands are similar in structure, but not identical, to eccrine glands. They are found in the axillae, in the anogenital region, and, as modified glands, in the external ear canal (ceruminous glands), the eyelid (Moll's glands), and the breast (mammary glands). They produce odor and do not function prior to puberty, which means they probably serve a vestigial function. The mammary gland is considered a modified and highly specialized type of apocrine gland.
Hair follicles are complex structures formed by the epidermis and dermis. (See the image below.) They are found over the entire surface of the body except the soles of the feet, palms, glans penis, clitoris, labia minora, mucocutaneous junction, and portions of the fingers and toes. Sebaceous glands often open into the hair follicle rather than directly onto the skin surface, and the entire complex is termed the pilosebaceous unit. [1, 4, 5]
Caucasian hair follicles are oriented obliquely to the skin surface, whereas the hair follicles of black persons are oriented almost parallel to the skin surface. Asian persons have vertically oriented follicles that produce straight hairs. These anatomic variations are an important consideration in avoiding alopecia when making incisions in the scalp.
The base of the hair follicle, or hair bulb, lies deep within the dermis and, in the face, may actually lie in the subcutaneous fat. This accounts for the remarkable ability of the face to re-epithelialize even the deepest cutaneous wounds. A band of smooth muscle, the arrector pili, connects the deep portion of the follicle to the superficial dermis. Contraction of this muscle, under control of the sympathetic nervous system, causes the follicle to assume a more vertical orientation.
Hair growth exhibits a cyclical pattern. The anagen phase is the growth phase, whereas the telogen phase is the resting state. The transition between anagen and telogen is termed the catagen phase. Phases vary in length according to anatomic location, and the length of the anagen phase is proportional to the length of the hair produced. At any one time at an anatomic location, follicles are found in all 3 phases of hair growth. This is extremely important for laser hair removal, because follicles in the anagen phase are susceptible to destruction, whereas resting follicles are more resistant. This explains why multiple treatments of an area may be necessary to ensure adequate hair removal.
Cutaneous Blood Supply
Cutaneous vessels ultimately arise from underlying named source vessels. Each source vessel supplies a 3-dimensional vascular territory from bone to skin termed an angiosome. Adjacent angiosomes have vascular connections via reduced caliber (choke) vessels or similar caliber (true) anastomotic vessels. The cutaneous vessels originate either directly from the source arteries (septocutaneous or fasciocutaneous perforators) or as terminal branches of muscular vessels (musculocutaneous perforators).
During their course to the skin, the cutaneous vessels travel within or adjacent to the connective tissue framework and supply branches to each tissue with which they come into close contact (bone, muscle, fascia, nerve, fat). They emerge from the deep fascia in the vicinity of the intermuscular or intramuscular septa or near tendons and travel toward the skin, where they form extensive subdermal and dermal plexuses. The dermis contains horizontally arranged superficial and deep plexuses, which are interconnected via communicating vessels oriented perpendicular to the skin surface. Cutaneous vessels ultimately anastomose with other cutaneous vessels to form a continuous vascular network within the skin. Clinically, this extensive horizontal network of vessels allows for random skin flap survival. [6, 7, 8]
In addition to the skin's natural heat conductivity and loss of heat from the evaporation of sweat, convection from cutaneous vessels is a vital component of thermoregulation. Cutaneous blood flow is 10-20 times that required for essential oxygenation and metabolism, and large amounts of heat can be exchanged through the regulation of cutaneous blood flow. The thermoregulatory center in the hypothalamus controls vasoconstriction and vasodilatation of cutaneous vessels through the sympathetic nervous system.
Skin lymphatics parallel the blood supply and function to conserve plasma proteins and scavenge foreign material, antigenic substances, and bacteria. Blind-ended lymphatic capillaries arise within the interstitial spaces of the dermal papillae. These unvalved, superficial dermal vessels drain into valved deep dermal and subdermal plexuses. These then coalesce to form larger lymphatic channels, which course through numerous filtering lymph nodes on their way to join the venous circulation near the subclavian vein – internal jugular vein junction bilaterally.
Sensory perception is critically important in the avoidance of pressure, mechanical or traumatic forces, and extremes of temperature. Numerous specialized structures are present in the skin to detect various stimuli. As previously mentioned, Merkel cells of the epidermis detect light touch. Meissner corpuscles also detect light touch. These are found in the dermal papillae and are most concentrated in the fingertips. Pacini corpuscles are found deep within the dermis or even in the subcutaneous tissue. These structures are specialized to detect pressure.
Pain is transmitted through naked nerve endings located in the basal layer of the epidermis. Krause bulbs detect cold, whereas Ruffini corpuscles detect heat. Heat, cold, and proprioception also are located in the superficial dermis. Cutaneous nerves follow the route of blood vessels to the skin. The area supplied by a single spinal nerve, or a single segment of the spinal cord, is termed a dermatome. Adjacent dermatomes may overlap considerably, which is important to note when performing field blocks with local anesthesia. [1, 9]
Lines and creases are evident over major and minor joints. Skin contraction produces wrinkles and creases that lie perpendicular to the underlying muscular vector force. Relaxed skin tension lines (RSTL), however, are formed during relaxation and often follow a different direction than age and contracting wrinkles. (See the image below.) Relaxed skin tension lines are created by the natural tension on the skin from underlying structures. 
Papillary ridges on the tips of the digits of the hands and feet and the surface of palms and soles are often used for personal identification. These are also known as friction ridges, since they assist in the ability to grasp. They are formed during fetal development and are unique to each individual, including identical twins. This distinct pattern does not change with aging. Stratum mucosum composes the outer surface of the ridges with underlying dermal papillae. Sweat pores are usually located at the top of the ridges. 
The amount of melanin pigment in the skin determines an individual's skin color (skin phototype). Skin pigment can be inherited genetically or can be acquired through various diseases. Hormonal changes during pregnancy can also vary the amount of pigmentation.
The Fitzpatrick Scale is used to classify skin complexion and response to UV exposure. (See table 1, below.) This classification is based on a personal history of sunburning and suntanning.  This classification is used clinically for evaluation of facial skin pigmentation before resurfacing procedures and is important for predicting outcomes and adverse effects.
Table 1: The Fitzpatrick Scale (Open Table in a new window)
|I||White or freckled skin||Always burns, never tans|
|II||White skin||Burns easily, tans poorly|
|III||Olive skin||Mild burn, gradually tans|
|IV||Light brown skin||Burns minimally, tans easily|
|V||Dark brown skin||Rarely burns, tans easily|
|VI||Black skin||Never burns, always tans|
Anatomy of Aging Skin
Age-associated skin changes include thinning, skin laxity, fragility, and wrinkles. Sun-exposed areas demonstrate additional aging changes, including dyspigmentation, premature wrinkling, telangiectasia, and actinic elastosis.
Cutaneous aging is characterized by intrinsic and extrinsic processes. Intrinsic, or chronologic, aging is a genetically determined and inevitable process in skin, including photoprotected skin. Intrinsic aging naturally occurs and is exacerbated by extrinsic aging, which is environmentally induced.
Aging at the cellular level is thought to be related to cellular senescence, specifically, the shortening of telomeres (the terminal portions of chromosomes) with each cell cycle. Telomere shortening ultimately results in cell-cycle arrest or apoptosis once a critical length is reached.
Preventable environmental factors that amplify intrinsic aging include sun exposure and smoking. Long-term UV-A radiation exposure accelerates intrinsic aging via the formation of reactive oxygen species (ROS). ROS lead to inflammatory cytokines and the up-regulation of matrix metalloproteinases, which result in the breakdown of collagen. UV-B radiation can also contribute to this aging process by causing direct deoxyribonucleic acid (DNA) mutations.
Histopathologically, photoaging is manifest as flattening of the dermal-epidermal junction, resulting in decreased nutrient transfer between the layers, heliodermatitis or chronic inflammation, elongated and collapsed fibroblasts, disorganized collagen fibrils with overall decrease in collagen levels, and the accumulation of abnormal elastin-containing material termed solar elastosis. [13, 14]