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The epidermis is the outermost of the three layers that make up the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have differe ...

skin
, the inner layers being the
dermis The dermis or corium is a layer of skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such a ...
and hypodermis. The epidermis layer provides a barrier to
infection An infection is the invasion of an organism's body Tissue (biology), tissues by Pathogen, disease-causing agents, their multiplication, and the reaction of host (biology), host tissues to the infectious agents and the toxins they produce. An inf ...
from environmental pathogens and regulates the amount of water released from the body into the
atmosphere An atmosphere (from the greek words ἀτμός ''(atmos)'', meaning 'vapour', and σφαῖρα ''(sphaira)'', meaning 'ball' or 'sphere') is a layer or a set of layers of gases surrounding a planet or other material body, that is held in ...
through transepidermal water loss. The epidermis is composed of multiple layers of flattened cells that overlie a base layer ( stratum basale) composed of columnar cells arranged perpendicularly. The rows of cells develop from
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type ...
s in the basal layer. Cellular mechanisms for regulating water and sodium levels ( ENaCs) are found in all layers of the epidermis. The word epidermis is derived through Latin , itself and . Something related to or part of the epidermis is termed epidermal. The human epidermis is a familiar example of
epithelium Epithelium () is one of the four basic types of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume ...
, particularly a stratified squamous epithelium.


Structure


Cellular components

The epidermis primarily consists of keratinocytes ( basal and differentiated suprabasal), which comprise 90% of its cells, but also contains melanocytes,
Langerhans cell Langerhans cells (LC) are tissue-resident macrophages of the skin, and contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the papillar ...
s, Merkel cells, and inflammatory cells. Epidermal thickenings called Rete pegs, Rete ridges (or rete pegs) extend downward between dermal papillae. Blood capillaries are found beneath the epidermis, and are linked to an arteriole and a venule. The epidermis itself has no circulatory system, blood supply and is nourished almost exclusively by diffused oxygen from the surrounding air.


Cell junctions

Epidermal cells are tightly interconnected to serve as a tight barrier against the exterior environment. The junctions between the epidermal cells are of the adherens junction type, formed by transmembrane proteins called cadherins. Inside the cell, the cadherins are linked to actin filaments. In immunofluorescence microscopy, the actin filament network appears as a thick border surrounding the cells, although the microfilament, actin filaments are actually located inside the cell and run parallel to the cell membrane. Because of the proximity of the neighboring cells and tightness of the junctions, the actin immunofluorescence appears as a border between cells.


Layers

The epidermis is composed of 4 or 5 layers, depending on the region of skin being considered.The Ageing Skin - Structure
/ref> Those layers in descending order are: * Keratin#Cornification, cornified layer (''stratum corneum'') ::Composed of 10 to 30 layers of polyhedral, anucleated corneocytes (final step of keratinocyte cell differentiation, differentiation), with the palms and soles having the most layers. Corneocytes contain a protein envelope (cornified envelope proteins) underneath the plasma membrane, are filled with water-retaining keratin proteins, attached together through desmosome, corneodesmosomes and surrounded in the extracellular space by stacked layers of lipids. Most of the barrier functions of the epidermis localize to this layer. * clear/translucent layer (''stratum lucidum'', only in palms and soles) ::This narrow layer is found only on the palms and soles. The epidermis of these two areas is known as "thick skin" because with this extra layer, the skin has 5 epidermal layers instead of 4. * granular layer (''stratum granulosum'') ::Keratinocytes lose their cell nucleus, nuclei and their cytoplasm appears granular. Lipids, contained into those keratinocytes within lamellar bodies, are released into the extracellular space through exocytosis to form a lipid barrier. Those polar lipids are then converted into non-polar lipids and arranged parallel to the cell surface. For example glycosphingolipids become ceramides and phospholipids become free fatty acids. * spinous layer (''stratum spinosum'') ::Keratinocytes become connected through desmosomes and produce lamellar bodies, from within the golgi apparatus, Golgi, enriched in polar lipids, glycosphingolipids, free sterols, phospholipids and catabolic enzymes. Langerhans cells, immunologically active cells, are located in the middle of this layer. * basal/germinal layer (''stratum germinativum, stratum basale/germinativum''). ::Composed mainly of proliferating and non-proliferating keratinocytes, attached to the basement membrane by hemidesmosomes. Melanocytes are present, connected to numerous keratinocytes in this and other strata through dendrites. Merkel cells are also found in the stratum basale with large numbers in touch-sensitive sites such as the fingertips and lips. They are closely associated with cutaneous nerves and seem to be involved in light touch sensation. The Malpighian layer (''stratum malpighi'') is both the stratum basale and stratum spinosum. The epidermis is separated from the dermis, its underlying tissue (biology), tissue, by a basement membrane.


Cellular kinetics


Cell division

As a stratified squamous epithelium, the epidermis is maintained by cell division within the stratum basale. cell differentiation, Differentiating cells delaminate from the basement membrane and are displaced outward through the epidermal layers, undergoing multiple stages of differentiation until, in the stratum corneum, losing their nucleus and fusing to squamous sheets, which are eventually shed from the surface (desquamation). Differentiated keratinocytes secrete keratin proteins, which contribute to the formation of an extracellular matrix that is an integral part of the skin barrier function. In normal skin, the rate of keratinocyte production equals the rate of loss, taking about two weeks for a cell to journey from the stratum basale to the top of the stratum granulosum, and an additional four weeks to cross the stratum corneum. The entire epidermis is replaced by new cell cell division, growth over a period of about 48 days.


Calcium concentration

Keratinocyte differentiation throughout the epidermis is in part mediated by a calcium gradient, increasing from the stratum basale until the outer stratum granulosum, where it reaches its maximum, and decreasing in the stratum corneum. Calcium concentration in the stratum corneum is very low in part because those relatively dry cells are not able to dissolve the ions. This calcium gradient parallels keratinocyte differentiation and as such is considered a key regulator in the formation of the epidermal layers. Elevation of extracellular calcium concentrations induces an increase in intracellular free calcium concentrations. Part of that intracellular increase comes from calcium released from intracellular stores and another part comes from transmembrane calcium influx, through both calcium-sensitive chloride channels and voltage-independent cation channels permeable to calcium. Moreover, it has been suggested that an extracellular calcium-sensing cell surface receptor, receptor (CaSR) also contributes to the rise in intracellular calcium concentration.


Development

Epidermal organogenesis, the formation of the epidermis, begins in the cells covering the embryo after neurulation, the formation of the central nervous system. In most vertebrates, this original one-layered structure quickly transforms into a two-layered tissue (biology), tissue; a temporary outer layer, the periderm, which is disposed once the inner basal layer or ''stratum germinativum'' has formed. This inner layer is a germ layer, germinal epithelium that gives rise to all epidermal cells. It divides to form the outer spinous layer (''stratum spinosum''). The cells of these two layers, together called the Malpighian layer(s) after Marcello Malpighi, divide to form the superficial granularity, granular layer (''Stratum granulosum'') of the epidermis. The cells in the stratum granulosum do not divide, but instead form skin cells called keratinocytes from the granule (cell biology), granules of keratin. These skin cells finally become the cornified layer (''stratum corneum''), the outermost epidermal layer, where the cells become flattened sacks with their nuclei located at one end of the cell. After birth these outermost cells are replaced by new cells from the stratum granulosum and throughout life they are shed at a rate of 0.001 - 0.003 ounces of skin flakes every hour, or 0.024-0.072 ounces per day. Epidermal developmental biology, development is a product of several growth factors, two of which are: * Transforming growth factor Alpha (TGFα) is an autocrine growth factor by which basal cells stimulate their own cell division, division. * Keratinocyte growth factor (KGF or FGF7) is a paracrine growth factor produced by the underlying dermis, dermal fibroblasts in which the cell proliferation, proliferation of basal cells is regulated.


Function


Barrier

The epidermis serves as a barrier to protect the body against microbial pathogens, oxidant stress (UV light), and chemical compounds, and provides mechanics, mechanical resistance to minor injury. Most of this barrier role is played by the stratum corneum. ;Characteristics * Physical barrier: Epidermal keratinocytes are tightly linked by cell junctions, cell–cell junctions associated to cytoskeletal proteins, giving the epidermis its mechanical strength. * Chemical barrier: Highly organized lipids, acids, hydrolytic enzymes, and antimicrobial peptides inhibit passage of external chemicals and pathogens into the body. * Immunologically active barrier: The humoral and cellular immunity, cellular constituents of the immune system found in the epidermis actively combat infection. * Water content of the stratum corneum drops towards the surface, creating hostile conditions for pathogenic microorganism growth. * An acidic pH (around 5.0) and low amounts of water make the epidermis hostile to many microorganic pathogens. * Non-pathogenic microorganisms on the surface of the epidermis help defend against pathogens by competing for food, limiting its availability, and producing chemical secretions that inhibit the growth of pathogenic microbiota. ;Permeability * Psychological stress (psychological), stress, through an increase in glucocorticoids, compromises the stratum corneum and thus the barrier function. * Sudden and large shifts in humidity alter stratum corneum tissue hydration, hydration in a way that could allow entry of pathogenic microorganisms.


Skin hydration

The ability of the skin to hold water is primarily due to the stratum corneum and is critical for maintaining healthy skin. Skin hydration is quantified using corneometry. Lipids arranged through a gradient and in an organized manner between the cells of the stratum corneum form a barrier to transepidermal water loss.


Skin color

The amount and distribution of melanin pigment in the epidermis is the main reason for variation in skin color in ''Homo sapiens''. Melanin is found in the small melanosomes, particles formed in melanocytes from where they are transferred to the surrounding keratinocytes. The size, number, and arrangement of the melanosomes vary between racial groups, but while the number of melanocytes can vary between different body regions, their numbers remain the same in individual body regions in all human beings. In white and Asian skin the melanosomes are packed in "aggregates", but in black skin they are larger and distributed more evenly. The number of melanosomes in the keratinocytes increases with UV radiation exposure, while their distribution remain largely unaffected.


Clinical significance

Laboratory culture of keratinocytes to form a 3D structure (artificial skin) recapitulating most of the properties of the epidermis is routinely used as a tool for drug development and testing.


Hyperplasia

Epidermal hyperplasia (thickening resulting from cell proliferation) has various forms: *Acanthosis is diffuse Epidermis (skin), epidermal hyperplasia (thickening of the skin, and not to be confused with acanthocytes).Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathologic Basis of Disease'' (7th ed.). Saunders. Page 1230. . It implies increased thickness of the Malpighian layer ( stratum basale and stratum spinosum). Acanthosis nigricans is a black, poorly defined, velvety hyperpigmentation, hyperpigmented acanthosis, usually observed in the back of neck, axilla, and other folded regions of the skin. *Focal epithelial hyperplasia (Heck's disease) is an asymptomatic, benign neoplastic condition characterized by multiple white to pinkish papules that occur diffusely in the oral cavity. *Pseudoepitheliomatous hyperplasia (PEH) is a benign condition characterized by hyperplasia of the epidermis and epithelium of skin appendages, with irregular squamous strands extending down into the dermis, and closely simulating squamous cell carcinoma (SCC). File:Acanthosis-nigricans4.jpg, Acanthosis nigricans File:Hecks disease.jpg, Heck's disease File:Histopathology of pseudoepitheliomatous hyperplasia, low magnification.jpg, Pseudoepitheliomatous hyperplasia (PEH), low magnification, with acanthotic squamous epithelium with irregular thick finger-like downgrowths into the underlying dermis. File:Histopathology of pseudoepitheliomatous hyperplasia, high magnification.jpg, PEH, high magnification, with reactive-appearing squamous downgrowths with no significant cytologic atypia. In contract, hyperkeratosis is a thickening of the stratum corneum, and is not necessarily due to hyperplasia.


Additional images


See also

* Skin repair


References

{{DEFAULTSORT:Epidermis (Skin) Skin anatomy