Epidermis

Cellular components The epidermis primarily consists of keratinocytes Blood capillaries 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 boundaries 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, Those layers from outermost to innermost are: They are attached together by corneodesmosomes. These corneocytes have a protein envelope that has now replaced the plasma membrane and are filled with water-retaining keratin proteins. Additionally, they are surrounded in the extracellular space by stacked layers of lipids, which in turn yields a water-retaining barrier. 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 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 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. 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. 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, 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; a temporary outer layer, the embryonic 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 (stratum spinosum). 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. Epidermal 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 division. • Keratinocyte growth factor (KGF or FGF7) is a paracrine growth factor produced by the underlying dermal fibroblasts in which the proliferation of basal cells is regulated. == Function ==

Barrier The epidermis serves as a barrier to protect the body against microbial pathogens, oxidative stress (UV light), and chemical compounds, and provides mechanical resistance to minor injury. Most of this barrier role is played by the stratum corneum. • Sudden and large shifts in humidity 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. 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. Touch The skin contains specialized epidermal touch receptor cells called Merkel cells. Historically, the role of Merkel cells in sensing touch has been thought to be indirect, due their close association with nerve endings. However, recent work in mice and other model organisms demonstrates that Merkel cells intrinsically transform touch into electrical signals that are transmitted to the nervous system. ==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 epidermal hyperplasia (thickening of the skin, and not to be confused with acanthocytes). It implies increased thickness of the Malpighian layer (stratum basale and stratum spinosum). 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 appendages, 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 contrast, hyperkeratosis is a thickening of the stratum corneum, and is not necessarily due to hyperplasia. ==Additional images==