The epidermis is the outermost of the three layers that comprise 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 diffe ...

, the inner layers being the dermis and

hypodermis The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macro ...

. The epidermis layer provides a barrier to

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable d ...

from environmental pathogens and regulates the amount of water released from the body into the

atmosphere An atmosphere () is a layer of gas or layers of gases that envelop a planet, and is held in place by the gravity of the planetary body. A planet retains an atmosphere when the gravity is great and the temperature of the atmosphere is low. ...

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 layers 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 of ...

s in the basal layer. The human epidermis is a familiar example of epithelium, particularly a stratified squamous epithelium. The word epidermis is derived through Latin , itself and . Something related to or part of the epidermis is termed epidermal.

Structure

Cellular components

The epidermis primarily consists of

keratinocytes Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...

( proliferating basal and differentiated suprabasal), which comprise 90% of its cells, but also contains

melanocyte Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and hear ...

Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells 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 th ...

Merkel cell Merkel cells, also known as Merkel-Ranvier cells or tactile epithelial cells, are oval-shaped mechanoreceptors essential for light touch sensation and found in the skin of vertebrates. They are abundant in highly sensitive skin like that of the f ...

s, and inflammatory cells. Epidermal thickenings called Rete ridges (or rete pegs) extend downward between dermal papillae.

Blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...

capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...

are found beneath the epidermis, and are linked to an arteriole and a venule. The epidermis itself has no blood supply and is nourished almost exclusively by diffused oxygen from the surrounding air. Cellular mechanisms for regulating water and sodium levels ( ENaCs) are found in all layers of the epidermis.

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 Actin is a protein family, family of Globular protein, globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in myofibril, muscle fibrils. It is found in essentially all Eukaryote, eukaryotic cel ...

filaments. In immunofluorescence microscopy, the actin filament network appears as a thick border surrounding the cells, although the 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 from outermost to innermost are: ; cornified layer ('' stratum corneum''): Confocal image of the stratum corneum

Composed of 10 to 30 layers of polyhedral, anucleated corneocytes (final step of keratinocyte differentiation), with the palms and soles having the most layers. Corneocytes contain a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

envelope (cornified envelope proteins) underneath the plasma membrane, are filled with water-retaining

keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ...

proteins, attached together through 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''): Confocal image of the stratum granulosum

Confocal image of the stratum granulosum

Keratinocytes lose their nuclei and their

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

appears granular. Lipids, contained into those keratinocytes within lamellar bodies, are released into the extracellular space through

exocytosis Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + '' cytosis''). As an active transport mechanism, exocytosis requires the use ...

to form a lipid barrier that prevents water loss from the body as well as entry of foreign substances. 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 The stratum spinosum (or spinous layer/prickle cell layer) is a layer of the epidermis found between the stratum granulosum and stratum basale. This layer is composed of polyhedral keratinocytes. These are joined with desmosomes. Their spiny ( ...

''):

Confocal image of the stratum spinosum with some basal cell clusters

Keratinocytes become connected through desmosomes and produce lamellar bodies, from within the 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 basale/germinativum''): Confocal image of the stratum basale showing some papillae

Confocal image of the stratum basale showing some papillae

Composed mainly of proliferating and non-proliferating keratinocytes, attached to the

basement membrane The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tissues including mesothelium and ...

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. ; Malpighian layer (''stratum malpighii''): This is usually defined as both the stratum basale and

. The epidermis is separated from the dermis, its underlying tissue, by a

Cellular kinetics

Cell division

As a stratified squamous epithelium, the epidermis is maintained by

cell division Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...

within the stratum basale. Differentiating cells delaminate from the

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 Desquamation occurs when the outermost layer of a tissue, such as the skin, is shed. The term is . Physiologic desquamation Keratinocytes are the predominant cells of the epidermis, the outermost layer of the skin. Living keratinocytes reside in ...

). 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 growth over a period of about 48 days.

Calcium concentration

Keratinocyte differentiation throughout the epidermis is in part mediated by a

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

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 receptor (CaSR) also contributes to the rise in intracellular calcium concentration.

Development

Epidermal

organogenesis Organogenesis is the phase of embryonic development that starts at the end of gastrulation and continues until birth. During organogenesis, the three germ layers formed from gastrulation (the ectoderm, endoderm, and mesoderm) form the internal ...

, the formation of the epidermis, begins in the cells covering the

embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...

after neurulation, the formation of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

. In most vertebrates, this original one-layered structure quickly transforms into a two-layered 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 germinal epithelium that gives rise to all epidermal cells. It divides to form the outer spinous layer (''

''). The cells of these two layers, together called the Malpighian layer(s) after Marcello Malpighi, divide to form the superficial 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 A granule is a large particle or grain. It can refer to: * Granule (cell biology), any of several submicroscopic structures, some with explicable origins, others noted only as cell type-specific features of unknown function ** Azurophilic granul ...

s of

. 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 Life is a quality that distinguishes matter that has biological processes, such as Cell signaling, signaling and self-sustaining processes, from that which does not, and is defined by the capacity for Cell growth, growth, reaction to Stimu ...

they are shed at a rate of 30 - 90 milligrams of skin flakes every hour, or 0.720 - 2.16 grams per day. Epidermal development is a product of several

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for r ...

s, two of which are: * Transforming growth factor Alpha ( TGFα) is an autocrine growth factor by which basal cells stimulate their own division. *

Keratinocyte growth factor The keratinocyte growth factor (KGF), also known as FGF7, is a growth factor present in the epithelialization-phase of wound healing. In this phase, keratinocytes are covering the wound, forming the epithelium. KGF is a small signaling molecule t ...

(KGF or FGF7) is a paracrine growth factor produced by the underlying dermal

fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of ...

s in which the

proliferation Proliferation may refer to: Weapons *Nuclear proliferation, the spread of nuclear weapons, material, and technology *Chemical weapon proliferation, the spread of chemical weapons, material, and technology * Small arms proliferation, the spread of ...

of basal cells is regulated.

Function

Barrier

The epidermis serves as a barrier to protect the body against microbial pathogens,

oxidant stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

( UV light), and

chemical A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wit ...

compounds, and provides 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–cell junctions associated to cytoskeletal proteins, giving the epidermis its mechanical strength. * Chemical barrier: Highly organized lipids, acids, hydrolytic enzymes, and

antimicrobial peptides Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for a ...

inhibit passage of external chemicals and pathogens into the body. * Immunologically active barrier: The humoral and cellular constituents of the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...

found in the epidermis actively combat infection. * Water content of the stratum corneum drops towards the surface, creating hostile conditions for pathogenic

microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...

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 Food is any substance consumed by an organism for nutritional support. Food is usually of plant, animal, or fungal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals. The substance is ...

, limiting its availability, and producing chemical

secretions 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classica ...

that inhibit the growth of pathogenic microbiota. ;Permeability *

Psychological Psychology is the scientific study of mind and behavior. Psychology includes the study of conscious and unconscious phenomena, including feelings and thoughts. It is an academic discipline of immense scope, crossing the boundaries betw ...

stress, through an increase in glucocorticoids, compromises the stratum corneum and thus the barrier function. * Sudden and large shifts in

humidity Humidity is the concentration of water vapor present in the air. Water vapor, the gaseous state of water, is generally invisible to the human eye. Humidity indicates the likelihood for precipitation, dew, or fog to be present. Humidity dep ...

alter stratum corneum 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 Corneometry is a widely practiced method for the measurement of skin hydration. It uses a capacitive sensor to measure the relative permittivity The relative permittivity (in older texts, dielectric constant) is the permittivity of a material ...

. Lipids arranged through a

gradient In vector calculus, the gradient of a scalar-valued differentiable function of several variables is the vector field (or vector-valued function) \nabla f whose value at a point p is the "direction and rate of fastest increase". If the gr ...

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 A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at some stage in their use. Generally dyes are often organic compounds whereas pigments are often inorganic comp ...

in the epidermis is the main reason for variation in skin color in ''

Homo sapiens Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

''. 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 A laboratory (; ; colloquially lab) is a facility that provides controlled conditions in which scientific or technological research, experiments, and measurement may be performed. Laboratory services are provided in a variety of settings: physici ...

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 A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhal ...

development and testing.

Hyperplasia

Epidermal hyperplasia (thickening resulting from cell proliferation) has various forms: *Acanthosis is diffuse 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

). Acanthosis nigricans is a black, poorly defined, velvety 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 appendage Skin appendages (or adnexa of skin) are anatomical skin-associated structures that serve a particular function including sensation, contractility, lubrication and heat loss in animals. In humans, some of the more common skin appendages are hairs ...

s, 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

References

{{DEFAULTSORT:Epidermis (Skin) Skin anatomy