Home - General information on skin
The skin is the largest human organ. It covers between 1.5 and 2 m2 , comprising about one sixth of total body weight.
Function of Skin
The skin performs a complex role in human physiology:
- serves as a barrier to the environment, and some glands (sebaceous) may have weak anti-infective properties.
- acts as a channel for communication to the outside world.
- protects us from water loss, friction wounds, and impact wounds.
- uses specialized pigment cells to protect us from ultraviolet rays of the sun.
- produces vitamin D in the epidermal layer, when it is exposed to the sun's rays.
- helps regulate body temperature through sweat glands.
- helps regulate metabolism.
- has esthetic and beauty qualities.
The skin consists of three functional layers:
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Epidermis
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Dermis or corium
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Subcutis (hypodermis)
In these layers are found the epidermal appendages: nails, hair and glands. (Note: Sebaceous and sweat glands belong to the exocrine glands. Sebaceous glands are nearly always connected to hair follicles. Sweat glands deliver their secretions directly to the skin surface.) The skin performs various functions such as temperature regulation and insulation, energy storage, sensory perception and protection from environmental influences such as fungi, bacteria and (UV) radiation.
The skin is composed of several layers. The lowest layer is called the dermis. This layer is composed of connective tissue, blood vessels, nerve endings, hair follicles, and sweat and oil glands. (1-Epidermis; 2-Dermis;3-Subcutis;4-Hair follicle;5-Sebaceous gland;6-Sweat gland)
Skin Cell Types
Keratinocytes
The most abundant cell type of the epidermis is the keratinocyte. These cells produce keratin proteins that provide some of the rigidity of the outer layers of the skin. Keratinocytes also form the bulk of the material in hair follicles. Dandruff and hair are dead keratinocytes.
Fibroblasts
The dermis is produced largely by fibroblasts, which during embryonic development are part of the mesenchyme. The fibroblasts produce the collagens and elastins that make skin very durable, from within.
Melanocytes
Melanocytes are cells in low abundance in the epidermis that produce the pigment melanin. The pigment made in melanocytes is transferred to the cells of the hair or epidermis. The melanin granules are injected into (or ingested by) the keratinocyte cells. There, the melanin granules accumulate around the nucleus of each keratinocyte.
Melanin absorbs harmful ultraviolet (UV) light before the UV radiation can reach the nucleus. Melanin protects the DNA in the nucleus from UV radiation damage. When melanin is produced and distributed properly in the skin, dividing cells are protected from mutations that might otherwise be caused by harmful UV light.
Differences in skin color are due mostly to differences in the types and amount of pigment in our keratinocytes. Skin darkening (tanning) from sun exposure is caused by the movement of existing melanin into keratinocytes, and by increased production of melanin by the melanocyte.
During embryonic development these cells migrate from the neural crest into the skin.
Langerhans cells
These are star-shaped resident immune cells, macrophages. A macrophage is a cell that protects your body from injury or illness. Macrophages break up or destroy (phagocytise) the invading organisms. These macrophages process the invading organisms and present antigens to the T-lymphocytes. The T-lymphocytes are immune-system cells which ultimately identify a substance as foreign or dangerous to the body.
Merkel's Cells
Only a few of these cells are present in skin; they are more numerous in the palms and soles (feet). These cells are probably sensory mechanical receptors that respond to stimulus, such as pressure or touch.
Schematic Drawing of Human Skin
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Drawing (transverse section) of human skin illustrates the epidermis, basement membrane, dermis, capillaries and major cellular components. A: Epidermis || B: Dermis || C: Cornified layer of keratinocytes (stratum corneum) || D: Suprabasal keratinocytes || E: Basal layer of keratinocytes (stratum basale) || F: Basement membrane G: Collagen fibers in dermis || H: Capillary (enclosed by a single microvascular endothelial cell) || I: Melanocyte || J: Dermal Fibroblast |
The great majority of cells in the epidermis are keratinocytes, which are arranged in stratified layers. At the dermal-epidermal junction is a single layer of keratinocytes with a small number of interspersed melanocytes (approximately 1/30) called the stratum basale. This basal layer of keratinocytes is also called the stratum germinativum, because it is where new keratinocytes are generated by cell proliferation. Three types of keratinocytes in the stratum basale have been defined by kinetic analysis: stem cells, transient-amplifying cells and committed cells. Stem cells, which represent ~ 10% of the basal cell population, generate daughter cells from mitosis that are either stem cells themselves or transient-amplifying cells. Transient-amplifying cells, which represent ~40% of the basal cell population, replicate with much higher frequency than stem cells, but are capable of only a few population doublings. Transient-amplifying cells produce daughter cells that are committed to terminally differentiate. These committed cells detach from the basement membrane, differentiate, and ultimately cease to proliferate as they migrate toward the skin surface, where they are sloughed off as dead, cornified cells called squames.
Keratinocyte stem cells (like stem cells from other tissues) are relatively undifferentiated, both biochemically and histologically. Although keratinocyte stem cells have a high capacity for cell division, they divide with much lower frequency than transient-amplifying cells. Thus, when labeled with 3H-thymidine, stem cells retain nuclear label for long periods of time compared to transient-amplifying cells. Therefore, stem cells have been described as "label-retaining" cells. Because stem cells are undifferentiated, biochemical markers of stem cells are difficult to identify. However, keratin 19 expression has been suggested as a marker of keratinocyte stem cells, based on localization of keratin 19 expression to 3H-thymidine label-retaining cells. Keratinocyte stem cells may also express higher amounts of the a2 and a3 integrins, because an approximate 1.5-fold increase in the expression of these integrins has been observed in keratin 19-expressing cells relative to other epidermal basal cells. The retention and expansion of keratinocyte stem cells in culture is thought to be essential for using keratinocytes in ex vivo gene therapy.
The Epidermis
As the outermost skin layer, the epidermis forms the actual protective covering against environmental influences. Its thickness averages 0.1 mm. On the face it is only 0.02 mm, while on the soles of the feet between 1 and 5 mm.
Though paper thin, the epidermis is composed of many layers of cells. In the basal layer (the living epidermis), new cells are constantly being reproduced, pushing older cells to the surface. As skin cells move farther away from their source of nourishment, they flatten and shrink. They lose their nuclei, move out of the basal layer to the horny layer (the dead epidermis), and turn into a lifeless protein called keratin. After serving a brief protective function, the keratinocytes are imperceptibly sloughed off. This process of a living cell's evolution, called keratinization, takes about 4 weeks.
The epidermis consists of up to 90 percent keratinocytes, the actual epidermal cells or dead skin cells, that are held together by what are called desmosomes. Keratinocytes function as a barrier, keeping harmful substances out and preventing water and other essential substances from escaping the body. The other 10 percent of epidermal cells are melanocytes, which manufacture and distribute melanin, the protein that adds pigment to skin and protects the body from ultraviolet rays. Skin color is determined by the amount of protein produced by these cells, not by the number of melanocytes, which is fairly constant in all races.
Hair and nails are specialized keratin structures and are considered part of the epidermis. While animals use fur and claws for protection and defense, these corresponding structures are largely cosmetic in humans. The skin, however, is uniquely human, since it can betray emotion by blushing (embarrassment), turning red (anger), blanching (fear), sweating (tension), and forming goosebumps (terror).
On the skin surface are the sweat gland pores (100-200/cm2) and the openings of the sebaceous glands (50-100/cm2). Their secretions ensure skin moisture and oiliness, and thus maintain the hydrolipid film. The epidermis itself has no blood vessels, so the nutrients are supplied through the fine blood vessels in the dermal papillae.
The epidermis is differentiated into five layers:
Schematic diagram of the epidermis: the basal cells change, through differentiation, into flat horny skin cells that are without nuclei. 3 Granular layer /4 Prickle-cell layer 5 Basal layer / 6 Basal membrane |
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Horny layer (stratum corneum)
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Clear layer (stratum lucidum)
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Granular layer (stratum granulosum)
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Prickle-cell layer (stratum spinosum)
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Basal layer (stratum basale)
Differentiation and skin regeneration
Through differentiation, the living, cylindrical basal cells lose their nuclei and become flattened cornified cells, changing their shape and composition in the process. The cells pass through the barrier zone, the border zone between the living epidermal layers and the horny layer, where the epidermal lipids are released.
Did you know that 90% of household dust is dead skin cells? Keratinocytes contain structural protein (keratin) and become progressively flattened as they advance upward from the basal layer to the corneal layer. The epidermis renews itself every 28 days through continual reproduction, differentiation / cornification and desquamation (mechanical sloughing-off of the uppermost horny cell layer).
The epidermis is a stratified squamous epithelial tissue. This means that it has several layers of epithelial cells and that its outermost layer is made up of squamous (flat) epithelial cells.
Mitotic Activity: The layer adjacent to the dermis is known as the basal layer. The basal layer is made up of columnar epithelial cells. Since all of the mitotic (cell-multiplying) activity of the epidermis occurs in the basal layer, the basal layer is often called the germinative layer. This mitotic activity involves about 4 percent of the cells in the basal layer at any given time. It occurs primarily between midnight and 0400 hours.
Migration of Cells to the Surface:
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Scanning electron microscope image of scaling horny skin cells. |
Over a period of weeks, new cells gradually migrate from the basal layer to the surface. During this migration to the surface, the cells change in shape from the original columnar to cuboidal and then finally to squamous. As the cells become squamous in form, they also become hardened, or cornified, through the development of a special type of protein. As they approach the surface, they die. Thus, the outermost layers of the epidermis are dead, horny scales.
Keratinocytes
Keratinocytes are stratified, squamous, epithelial cells which comprise skin and mucosa, including oral, esophageal, corneal, conjunctival, and genital epithelia. Keratinocytes provide a barrier between the host and the environment. They prevent the entry of toxic substances from the environment and the loss of important constituents from the host. Keratinocytes differentiate as they progress from the basal layer to the skin surface. The normal turnover time for keratinocytes is around 30 days but epidermal turnover may be accelerated in some skin diseases such as psoriasis.
Keratinocyte stem cells reside in the basal layer. These cells have a low rate of mitosis and give rise to a population of transient amplifying cells. (Figure 1) Transient amplifying cells go through a limited number of divisions, differentiate, and move up in the epidermis. The cells above the basal layer are known as the spinous layer. Under routine microscopy small bridges, resembling spines, can be seen between the keratinocytes which represent intercellular adhesion complexes known as desmosomes. As the cells further differentiate, they synthesize keratohyaline granules, a prominent feature of cells in the granular layer. Proteins synthesized in the granular layer are important in the final stages of epidermal differentiation and include profilagrin, loricrin, involucrin, and cornifin. These molecules are important in the formation of the stratum corneum, the outer most layer of the epidermis.
Keratin
Electron microscopical examination of cells from all tissues reveals that they contain a complex, heterogenous, intracytoplasmic system of filaments. The components of this system include actin, myosin, and tubulin, whose diameters average approximately 60A°, 150A°, and 250A°, respectively. In addition, other intracytoplasmic filaments were noted, and since the diameter of these latter structures was found to be between 70 and 100A°, they were called intermediate filaments.
Intermediate filaments form a major part of the cytoskeleton of most cells and fulfill a variety of roles related to cell shape, spatial organization, and perhaps informational transfer. The nucleus contains structures related to these intermediate filaments and many intracellular components including polyribosomes, mitochondria, nucleic acids, enzymes, and cyclic nucleotides are attached to the cytoskeleton.
Based on their biochemical, biophysical, and antigenic properties, a number of classes of intermediate filaments can be recognized in different cell types: desmin (skeletin) in muscle cells, glial fibrillary acidic filaments in glial cells, neurofilaments in neurons, vimentin in mesenchymal cells, and keratin in epithelial cells. In cultured epidermal cells, keratins account for up to 30% of the cellular protein, while in stratum corneum, keratin accounts for up to 85% of the cellular protein.
At least 19 keratin proteins can be identified ranging in molecular weight from approximately 40,000 to 68,000 micrograms. Moll and his coworkers published their human keratin catalogue in 1982. According to this catalogue, there are two keratin subfamilies. The molecular weight of the members of one (the basic subfamily) is relatively larger than that of the members of the other (the acidic subfamily). Each of the keratins is the product of a unique gene and, in essentially all situations, the keratins are expressed as pairs containing one member of each subfamily. The two members of each pair are in the same size rank order within their respective family, e.g., the largest acidic keratin is expressed with the largest basic.
The type of keratin differs in different tissues, i.e, there are different types of keratin for keratinized epidermis, hyperproliferative epidermis of palms and soles, corneal epithelium, stratified epithelium of the esophagus and cervix, and simple epithelium of the epidermal glands. As mentioned before, keratin is the main structural protein of the epidermis.
The Subcutis (Hypodermis)
The subcutis (sub = under; cutis = skin/Lat.) refers to the fat tissue below the skin. It consists of spongy connective tissue interspersed with energy-storing adipocytes (fat cells).
Fat cell clusters
Fat cells are grouped together in large cushion-like clusters held in place by collagen fibres called connective tissue septa or sheaths.
Nourishment, insulation and padding
The subcutis is heavily interlaced with blood vessels, ensuring a quick delivery of stored nutrients as needed. The functions carried out by the subcutaneous fatty tissue, beside the storage of nutrients in the form of liquid fats, include the insulation of the body from cold and shock absorption. On the palms of the hand, the soles of the feet and the buttocks, fat padding serves almost exclusively for shock absorption. (Note: Fats, also triglycerides or acylglycerins, are the most plentiful and simplest fatty acid-containing lipids. They are esters of the triol alcohol, glycerine with three saturated and/or unsaturated fatty acids. Fats make up the main component of the fat depots.)
Fat distribution in men and women
The fat content of the subcutis is not the same in all body regions. Also men and women differ in the distribution of subcutaneous fat. An example is cellulite - it is characterized by a special arrangement of the subcutaneous fat tissue septa and predisposes to fat deposition on the hips, thighs and buttocks - which occurs mostly in women. Men on the other hand tend to store fat on the torso.