The skin (dermis, cutis, derma, integument, and cuticle) is the largest organ of the human body (approximately 20 square feet), weighing approximately 16% of bodyweight. Skin thickness varies and is on average 1mm thick; the thinnest on eyelids at 0.5mm and the thickest at 1.5mm on the palms and soles. Skin consists of multiple layers (stratified), epidermis, dermis and hypodermis (deepest layer).
The upper most outer layer of the skin, the epidermis, consists of squamous cells (flat and scale-like in shape) and underneath basal cells (round shaped). The process of keratinisation (formation of horny layer) occurs over the course of 4 to 6 weeks when keratinocytes (85% of the epidermal cells) migrate upwards through the skin to be desquamated (shedding of old skin) at the skin surface. Renewal of the upper layer is continuously initiated by the keratinocytes.
The mitotic layer (single line) is the area where the division of keratinocytes takes place, held together by desmosomes (macula adherens) resisting shearing of the epidermal layer. Mitosis (cell division) occurs in the ratio of 1:2, with each keratinocyte producing two identical new cells. One cell remains in place to enable it to divide again, as the other migrates to the differentiation layer, the upper and thickest layer of the epidermis (5-15 cells thick). After initial growth, a newly formed layer, the Malphigian layer, gives rise to the production of keratin, an insoluble sulphur-based fibrous protein. In the Malphigian layer, Langerhans cells play a role in the recognition of antigens and interaction with epidermal T-cells (lymphocytes), as an immunologic response.
In the deepest layer of the epidermis, called the stratum basale, Merkel cells are found, these cells are part of the cell-neuron complex: a close association with an afferent nerve ending, the sensory part of the epidermis.
As the keratinocytes migrate upwards, they lose their content of the cell nucleus (anucleate) and become flat in structure. When reaching the outermost layer of the epidermis, the keratinocytes become corneocytes, with relatively little biological activity. This is the end-stage of the keratinocytes. The keratinocyte at this stage is filled with keratin and ceramides; these are lipids and fatty acids, enabling the dermis to retain moisture. The most external epidermal layer in contact with the external environment is the stratum corneum. The external corneocyte is distinguished in 2 layers, a compact and a sloughing layer. When the junction, corneodesmosomes, between these layers breaks down, desquamation (skin shedding) occurs.
Melanocytes and melanogenesis
The deeper layer of the epidermis contains the pigment producing (melanogenesis) cells, melanocytes. These produce the dark brown pigment in the epidermis, eumelanin. The melanocyte forms part of the epidermal unit in a ratio of 1:36 keratinocytes. Melanin production is initiated through the up regulation of the receptors on the melanocyte, called the melanocortin 1 receptor (MC1R). The melanocyte produces intracellular eumelanin through a tyrosinase mediated biochemical pathway. Once eumelanin is formed within the cell organelle melanosome, the eumelanin granules are transferred after dendrite formation by the melanocyte.
Melanin has a photoprotective function (shields against UV and light damage) to the skin. The second form of melanin is pheomelanin, reddish-yellow pigmentation. Pheomelanin is the major type of pigmentation in red hair and also predominates in the epidermis of skin types I and II (fair skinned individuals). Eumelanin, on the other hand, is present in large amounts in individuals with dark skin and hair (skin types III-VI). It is generally accepted that eumelanin provides greater photoprotection than pheomelanin.
The dermis is the deeper skin layer consisting of two layers: the papillary and elastic, both containing collagen. Blood vessels (capillaries) and nerves are found in this layer.
The principle structural component of the dermis is the protein collagen, produced by fibroblasts dispersed throughout the dermis. A quantity of collagen molecules are bundled together throughout the dermis, making up for three-quarters of the dry weight of skin. Collagen is mainly responsible for dermal strength, representing connective tissue, the glue or cement holding together smooth muscles tissues found throughout the body. Collagen is, along with elastin, a pivotal component of bones, cartilage, tendons, the skin, lung tissue and blood vessels. Most of all, collagen is the main structure to provide firmness to body tissues, while elastin provides flexibility to these tissues.
As part of the dermal sensory system, nerves transmit and evoke pain, itch, and temperature from the dermis. Specialized nerve cells, Meissner’s and Vater-Pacini corpuscles, transmit the sensations of touch and pressure. Also present in the dermis are eccrine, apocrine, sebaceous glands and hair follicles.
The hypodermis contains specialized cells and structures, and adnexae, such as hair follicles, each follicle being attached to the arector pili muscle. Oil, scent and sweat, sebaceous, apocrine and eccrine glands are all associated with the follicle. The hypodermis is characterized with a high density of lipocytes, adipose or fat cells. The adipose layer serves as the largest reservoir of fatty acids. There is gender difference in distribution and size of adipose cells (in females predominantly in the buttocks and thigh area; in males in the abdominal region). This hypodermis also contains sweat and eccrine glands.
Hair is regarded as “dead epidermal cells” that have evolved through continuous modified epidermal keratinization. Upon close examination, hair is characterized by the expression of specific keratin proteins that are intensely cross-linked by disulfide bonds. Hair stems from hair follicles, which are epidermal invaginations that project into the dermis or hypodermis. There are two types of hair: vellus – fine short, soft, fine, and pale hair; and terminal – thick hard, large, coarse, long and dark hair. The number of hairs on all primates is similar, but mostly seen is vellus on humans and terminal on other primates. Hair can be “mobilized” by arector pili muscles, a smooth muscle enabling hair to stand on end most likely for better insulation (the phenomenon of goose bumps/pimples). The hair follicle undergoes a cycle of active and resting phases during which a new hair is started and then falls out, respectively. Melanocytes are seen to be scattered throughout the hair shaft. The melanocytes render colour to the hair. With age, tyrosinase production decreases and the hair turns gray.
Eccrine sweat glands are simple coiled tubular glands located in the deep dermis or underlying hypodermis and are present throughout the body. They develop as invaginations of the epithelium of the epidermal ridge and grow into the dermis, and the deep aspect eventually develops into the glandular portion of the sweat gland. Eccrine sweat glands have two regions: a secretory region and a duct region. The secretory portion is comprised of simple coils of cuboidal epithelium containing two kinds of cells. Dark cells produce sialo-mucins, while clear cells produce water and electrolytes. Myoepithelial cells support and constrict the gland in response to cholinergic stimulation. Secretion is controlled by heat stress in most of the body but is under emotional control in palms and soles. The duct portion of the sweat gland is stratified cuboidal epithelium (2 layers), whose cells resorb ions (Na+, K+, Cl-) from the glandular secretion. The final product is hypotonic (99% water) containing salts, lactate and urea. Adults are able to produce between 0.5-1.0 litre/day. Apocrine sweat glands are simple tubular glands that empty into hair follicles in axillary and anogenital regions. The secretion is a mixture of proteins, carbohydrates, and ferric ions, odourless when secreted, but which is acted on by commensal bacteria. They begin to function at puberty; but their function remains unknown.
Function of the skin
Human skin has numerous functions, it is the major interface between the environment and the human organs and so it serves many specialised functions that facilitate survival. It regulates body temperature to protect against hyperthermia and hypothermia. Water loss is controlled to protect against dehydration and is involved in controlling a balance of body fluids, mineral and waste product loss.
Skin also protects from the invasion of noxious substances, UV light, heat and micro-organisms. Langerhans cells have been found to be involved in a number of reactions to protect against micro-organism invasion and pain. They have antigen-presenting capacity, force keratinocytes to secrete immune regulating cytokines and T-cells, and are involved in delaying hypersensitivity.
The skin is also the most extensive sensory organ of the body for detection of tactile, thermal and painful stimuli for the start of vitamin D production – which is pivotal for bone growth – and serves other important immunological functions. Wound healing of the skin is regulated by an intact immunological defense mechanism.
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