Introduction

The skin is the largest organ in the body, coveringits entire external surface.The skinhas3 layersthe epidermis, dermis, and hypodermis,which have different anatomical structures and functions (seeImage.Cross Section, Layers of the Skin). The skin's structure comprises an intricate network that serves as the body's initial barrier against pathogens, ultraviolet (UV) light, chemicals, and mechanical injury.This organ also regulates temperature and the amount of water released into the environment.

Skin thicknessvariesby body region and isinfluenced by the thickness of the epidermal and dermal layers. Hairless skin in the palms of the hands and soles of the feet is the thickest due to the presence ofthe stratum lucidum, an extra layer in the epidermis.Regions lacking this extra layer are considered thin skin. Of these regions, the back has the thickest skin because it has a thick epidermis.[1][2][3]The skin's barrier function makes it susceptible to various inflammatory and infectious conditions. In addition, wound healing, sensory changes, and cosmesis are significant surgical concerns. Understanding the skin's anatomy and function is crucial for managing conditions across all medical fields.

Epidermis

The epidermis, the skin's outermost layer, is composed ofseveral strata and various cell types crucial for its function.

Layers of the epidermis:From the deepest to the most superficial, the epidermal layers are the stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum. The stratum basale,also known asstratum germinativum, is separated from the dermis by the basement membrane (basal lamina) and attached to it by hemidesmosomes. The cells in this layer are cuboidal to columnar, mitotically active stem cells that constantly produce keratinocytes. This layer also contains melanocytes. The stratum spinosum, comprising 8to 10 cell layers, isalsocalled the prickle cell layer. This layer contains irregular, polyhedral cells with cytoplasmic processes, sometimes called spines,that extend outward and contact neighboring cells by desmosomes. Dendritic cells can be found in this layer.[4][5]

The stratum granulosum has 3to 5 cell layers and containsdiamond-shaped cells with keratohyalin and lamellar granules. Keratohyalin granules contain keratin precursors that aggregate, cross-link, and form bundles. The lamellar granules contain the glycolipids secreted to the cell surfaces, functioning as anadhesiveto maintain cellular cohesion. The stratum lucidumcomprises 2 to 3 cell layers and ispresent in thicker skin on the palms and soles. This thin and clear layer consists of eleidin, a transformation product of keratohyalin. The stratum corneum has 20to 30 cell layers and occupies the uppermost epidermal layer. The stratum corneumis composed of keratin and dead keratinocytes (anucleate squamous cells) that form horny scales. This layer has the most variable thickness, especially in callused skin. Dead keratinocytesrelease defensins within this layer, which are part of our first line of immune defense mechanisms.[6][7]

Cells of the epidermis:The epidermal cells include keratinocytes, melanocytes, and Langerhans and Merkel cells(seeImage.Cells of the Epidermis). Keratinocytes are the predominant cells of the epidermis,originating from the basal layer. These cells produce keratin and lipids essentialforformingthe epidermal water barrier. Keratinocytes also contribute to calcium regulation by enablingUVB light absorption in the skin,which iscriticalfor vitamin D activation. Melanocytes derive from neural crest cells and primarilysynthesize melanin, the main skin pigment component. These cells are found between stratum basale cells. UVB light stimulates melanin secretion, protecting against further UV radiation exposure and acting as a built-in sunscreen. Melaninforms during the conversion of tyrosine to dihydroxyphenylalanine by the enzyme tyrosinase. Melanin then travels from cell to cell, relying on the long processesconnecting the melanocytes to the neighboring epidermal cells. Melanin granules from melanocytestransit through the lengthy processes to the cytoplasm of basal keratinocytes. This transfer occurs through cytocrine secretion, where keratinocytes phagocytose the tips of melanocyte processes.

Langerhanscellsare dendritic cells that act as the skin's first-line cellular immune defenders andare crucialfor antigen presentation. Special stains allow visualization of these cells in the stratum spinosum. Langerhans cells are of mesenchymal origin, derived from CD34-positive bone marrow stem cells, and are part of the mononuclear phagocytic system.These cells contain Birbeck granules and tennis racket-shaped cytoplasmic organelles. Langerhans cells express major histocompatibility complex (MHC) I and MHC II molecules, uptake antigens in the skin, and transport them to the lymph nodes. Merkel cells are oval-shaped modified epidermal cells found in the stratum basale, directly above the basement membrane. These cells serve as mechanoreceptors for light touch and are found in the palms, soles, and oral and genital mucosa, with the highest concentration in the fingertips. Merkel cells bind toadjoining keratinocytes through desmosomes and contain intermediate keratin filaments. The cell membranes of Merkel cells interact with free nerve endings in the skin.

Dermis

The dermis is connected to the epidermisby the basement membrane.The dermis consists of 2 connective tissue layers, papillary and reticular, which merge without clear demarcation. Thepapillary layeris the upper dermal layer,which isthinner and composed of loose connective tissue that contacts the epidermis. Thereticular layeris the deeper layer, which is thicker and less cellular. This layer consists of dense connective tissuecomposedof collagen fiber bundles. The dermis houses the sweat glands, hair, hair follicles, muscles, sensory neurons, and blood vessels.

Hypodermis

The hypodermis, also known as the subcutaneous fascia, is located beneath the dermis.This layer is the deepest skin layer and contains adipose lobules,sensory neurons, blood vessels, and scanty skin appendages, such as hair follicles.

Functions

The skin's comprehensive roles highlight its complexity and importance in maintaining overall health and well-being.These roles are discussed below.[8][9]

Barrier function:The skin has multiple protective roles, acting as a barrier against various external threats. The skinshieldsthe body fromexcessive water loss or absorption, invasion by microorganisms, mechanical and chemical trauma, and UV light damage. The cell envelope establishes the epidermal water barrier, a layer of insoluble proteins on the inner surface of the plasma membrane. This barrier is formed through thecross-linkingof small proline-rich proteins. Larger proteins such as cystatin, desmoplakin, and filaggrincontribute to the barrier's robust mechanics. The lipid envelope is a hydrophobic layer attached to the outer surface of the plasma membrane. Keratinocytes in the stratum spinosum produce keratohyalin granules and lamellar bodies containing a mixture of glycosphingolipids, phospholipids, and ceramides assembled within Golgi bodies. The contents of lamellar bodies are then secreted through exocytosis into the extracellular spaces between the stratum granulosum and corneum.

Immunological defense:The skin plays a crucial role in both adaptive and innate immunity. In adaptive immunity, antigen-presenting cells initiate T-cell responses, leading to increased levels of helper T cells, such as TH1, TH2, or TH17. In innate immunity, the skin produces various peptides with antibacterial and antifungal properties. The skin-associated lymphoid tissue is a significant component of the immune system,aiding in preventing infections, as even minor skin breaks can lead to infection. Langerhans cellsare part of the adaptive immune system, presenting foreign antigens encountered in the skin to T cells.

Regulation of homeostasis:The skin plays a vital role in maintaining body temperature and water balance. This organregulates heat exchange with the environment, particularly through the blood vessels and sweat glands. The skin managesthe rate and amount of water evaporation and absorption.

Endocrine and exocrine functions:Keratinocytes produce vitamin D by converting 7-dehydrocholesterol under UV light exposure. These cells also express the vitamin D receptor and contain enzymes that activate vitamin D, essential for the proliferation and differentiation of keratinocytes. The skin's exocrine functions include temperature control by perspiration and skin protection by sebum production. Sweat and sebaceous glands are crucial to these functions.

Sensory functions:The skin is equipped with nociceptors that allow for the sensation of touch, heat, cold, and pain, facilitating interaction with the environment. The skin's sensory roles are essential for an individual's movement, protection, andinteraction with the environment.

Diagnostic indicator:Skin characteristics such aspigmentation, smoothness, elasticity, and turgor provide insights into an individual's overall health status. Skin assessment is often a crucialpartof a person's physical examination.[10][11]

Cell division, desquamation, and sheddingin the skin:Cell division occurs in the stratum basale. Basal cells (young keratinocytes)begin the synthesis of keratinous tonofilaments, whichare grouped into bundles called tonofibrils. Older keratinocytes are then pushed into the stratum spinosum after mitosis.Skincellsbegin toproduce keratohyalin granules with intermediate-associated proteins, filaggrin, and trichohyalin in the upper part of the spinous layer. Thisprocess helps aggregate keratin filaments and convert granular cells into cornified cells, known as keratinization. Cells also produce lamellar bodies during this stage.

Keratinocytescontinue to move into the stratum granulosum afterward, where they become flattened and diamond-shaped. The cells accumulate keratohyalin granules mixed between tonofibrils.Keratinocytesthen continue to the stratum corneum, flattening and losing organelles and nuclei. The keratohyalin granules turn tonofibrils into a homogenous keratin matrix.Cornified cells reach the surface and are desquamated when desmosomes disintegrate. The proteinase activity of kallikrein-related serine peptidase is triggered by lowered pH near the surface. The processes ofskinshedding and desquamation vary slightly by body region.Hairless skincomprisesmore layers, withtheadditionof thestratum lucidum. Thus, keratinocytes in body regions with hairless skin go through more layers before reaching the surface.[12][13]

The epidermisis derived from ectodermal tissue. The dermis and hypodermisare derived from mesodermal tissue from somites. The mesoderm is also responsible for the formation of Langerhans cells. Neural crest cells, responsible for specialized sensory nerve endings and melanocyte formation, migrate into the epidermis during epidermal development.[14][15]

Blood vessels and lymphatic vessels are found in the skin's dermal layer.Blood supply to the skin comprises 2 plexusesonebetween the papillary and reticular dermal layers and another between the dermis and subcutaneous tissues.Blood supply to the epidermis is through the superficial arteriovenous plexus (subepidermal/papillary plexus). These vessels are important for temperature regulation. The body regulates temperature by increasing blood flowto the skin, transferring heatfrom the bodyto the environment.The autonomic nervous system controls the changes in blood flow.Sympathetic stimulation results in vasoconstriction, resulting in heat retention.Conversely, vasodilationleads to heat loss. Vasodilation is the body's response to increased body temperature,resulting from inhibiting the sympathetic centers in the posterior hypothalamus. In contrast, decreased body temperature causes vasoconstriction.[16][17]

Nerves of the skin include both somatic and autonomic nerves. The somatic sensory systemtransmitspain (nociception), temperature, light touch, discriminative touch, vibration, pressure, and proprioception sensations to the central nervous system. Specialized cutaneous receptors and end organs mediate perception, including Merkel disks and Pacinian, Meissner, and Ruffini corpuscles. Autonomic innervation controls vasculature tone, hair root pilomotor stimulation, and sweating. The free nerve endings extend into the epidermis and are responsible for sensing pain, heat, and cold. These sensory structures are most numerous in the stratum granulosum layer andaround most hair follicles. Merkel disks sense light touch andreaches the stratum basale layer. The other nerve endings are found in the deeper portions of the skin and include the Pacinian, Meissner, and Ruffini corpuscles. The Paciniancorpusclessense deep pressure. The Meissner corpuscles sense low-frequency stimulation at the level of the dermal papillae.TheRuffini corpuscles sense pressure.[18][19][20]

The arrector pili muscles are bundles of smooth muscle fibers attached to the connective tissue sheath of hair follicles. Contraction of these muscles pulls the hair follicle outward, erecting the hair. The arrector pili also compress the sebaceous glands, facilitating sebum secretion. Hair does not exit perpendicularly but at an angle. The erection of hair, known as piloerection, produces goosebumps, giving the skin a bumpy appearance when exposed to cold temperatures.[21]Studies show that piloerection contributes to thermoregulation and stem cell growth.[22]

Langer lines, also known as cleavage lines, are topological lines used to defineskin tension.Theselines correspond to the alignment of collagen and elastic fibers in the reticular dermis. Less scarring occurs ifsurgical incisions are made along these lines.[23]

The skin's clinical significance spans all medical disciplines. A few are discussed below.

Dermatomes

Dermatomes areskin segments divided based on afferent nerve distribution, numbered according to spinal vertebral levels. Spinal nerves comprise8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygealnerve. Diseasessuch as shingles caused by varicella-zoster infection manifest pain and rashes in dermatomal patterns. Dermatomes also aid inlocalizing spinal injuries.

Squamous Cell Carcinoma

Squamous cell carcinoma is amalignancy arising from mutated keratinocytes,typically due to UV damage in individuals with type I or II skin types. These individuals typically have light skin, blue or green eyes, and red or blonde hair and burn without tanning.The lesions oftenappearasscaly, flaky, thick red patches that may bleed.Somesquamous cell carcinoma tumors resemble warts.This type of skin cancer can metastasize. Squamous cell carcinoma often arises from actinic keratosespremalignant lesions with cutaneous hornsdeveloping fromchronicUV damage.[24]

Basal Cell Carcinoma

Basal cell carcinoma is a malignant neoplasm of the basal layers of the epidermis. Unlikesquamous cell carcinoma, itis much less likely to metastasize.This type of skin cancer is more common in sun-exposed areas, often appearing as pearly papules on the face, with telangiectasias and a great tendency to ulcerate.

Melanoma

Melanoma is a highly invasive malignant melanocyte tumor that is fatal but rarer than skinsquamous cell carcinoma and basal cell carcinoma. This neoplasm's high metastatic potential is significantly mediated bylesiondepth.Melanoma can be found anywhere on the body and is typically irregularly pigmented but can be amelanotic.[25]

Langerhans Cell Histiocytosis

Langerhans cell histiocytosis is a type of cancer in which Langerhans cells accumulate in the body andformgranulomas, often in the bones, causing bone pain.These granulomas can also appear in the skin, producing rashes, erythematous papules, or blisters (seeImage.Histology, Trichodysplasia Spinulosa). Notably, Langerhans cellhistiocytosis can affect the pituitary gland, leading to diabetes insipidus, infertility, or other endocrine disorders due to hormone deficiencies. Pancytopenia is apotentially fatal Langerhans cellhistiocytosis complication, manifesting with anemia, thrombocytopenia, and leukocytopenia, caused by overcrowding of Langerhans cells in the bone marrow.[26]

Merkel Cell Carcinoma

Merkel cell carcinoma is an uncommon cancer of the Merkel cells. This tumor is categorized as a neuroendocrine small cell carcinoma. Clinically,Merkelcell carcinoma often presents as a painless, solitary cutaneous or subcutaneous nodule, sometimes with a cystic appearance. The nodule can be red, pink, violet, blue, or skin-colored. Lesions may ulcerate or have satellite lesions.Merkel cell carcinoma is typically smaller than 20 mm at diagnosis but shows rapid tumor growth over a few months.[27]

Pemphigus Vulgaris

Pemphigus vulgaris is an autoimmune disease that targets the desmosomes, the intercellular proteins connecting keratinocytes. Desmosome degradation results in acantholysis and the formation ofeasily ruptured blisters within the epidermis. The disease is characterized by a positive Nikolsky sign, where the epidermis peels away upon rubbing.

Bullous Pemphigoid

Bullous pemphigoid is a blistering disease that affects older adults, causing tense subepidermal blisters.The conditionis causedby antibodies targeting hemidesmosomes, which connect the epidermis to the dermis at the basement membrane. This condition is not acantholytic and does not show a positive Nikolsky sign.[28]

ScaldedSkinSyndrome

Scalded skin syndromearises fromthe effects of the exfoliative toxin released byStaphylococcal aureus. The condition manifests as generalized skin exfoliationwith apositiveNikolsky sign, a severely burned (intensely red) appearance, and fever.[29][30]

Drug Reactions

Various drug reactions manifest in the skin, including erythema multiforme and the syndromes of drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson, and toxic epidermal necrolysis. These conditions are often associated with certain medications, including sulfa-containing drugs,nonsteroidal anti-inflammatory drugs, and antiepileptics.[31][32]

The epidermis contains much of our normal flora,with the microbiome varying by body region. The microorganisms inhabiting our skin surfaces are nonpathogenic and can be commensal or mutualistic. The bacteria that tend to predominate are Staphylococcusepidermidis andS aureus, Cutibacterium acnes, Corynebacterium, Streptococcus, Candida, and Clostridium perfringens. However, infections may occur when the protective skin barrier is altered or breached.[33]

Histology, Trichodysplasia Spinulosa. The left column shows hematoxylin and eosin staining of healthy skin (A1) and trichodysplasia spinulosa lesional skin (B1) at low power. At high power, healthy (A2) and trichodysplasia spinulosa (B2) epidermis and (more...)

Cross Section, Layers of the Skin. This is a cross-section view of the hair follicles, hair roots and shafts, sweat glands, pores, epidermis, dermis, and hypodermis. The papillary and reticular layers are also included. The eccrine sweat gland is located (more...)

Cells of the Epidermis. The image shows stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, stratum basale, and dermis. Contributed by C Rowe

Disclosure: Hani Yousef declares no relevant financial relationships with ineligible companies.

Disclosure: Mandy Alhajj declares no relevant financial relationships with ineligible companies.

Disclosure: Adegbenro Fakoya declares no relevant financial relationships with ineligible companies.

Disclosure: Sandeep Sharma declares no relevant financial relationships with ineligible companies.

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Anatomy, Skin (Integument), Epidermis - StatPearls - NCBI Bookshelf

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