anatomy physiology of the skin

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    Anatomy & Physiologyof

    The Skin

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    Basic Science of the Epidermis

    The skin is composed of the 3 primarylayers: Epidermis, Dermis &Subcutaneous

    Each layerspecific characteristics &functions

    The Epidermis ->most superficial layer

    plays important role from a cosmeticstandpointgives the skins texture,moisturize and color

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    Basic Science of the Epidermis

    Knowledge of the basic structure of theEpidermis best enables a practitioner toimprove the appearance of patients skin

    In the future, study of these components islikely to lead to an enhancedunderstanding of skin aging and the

    effects of topical products on the biologicalfunction of the skin

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    The Keratinocyte

    Also known as corneocytes

    Born at the base of the epidermis at thedermal-epidermal junction / DEJ

    Produced by stem-cells, and slowly moveto the top

    These process of cells maturing andmoving to the top is called keratinization

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    The Keratinocyte

    As the cells move through the epidermisand mature, they develop differentcharacteristics

    The layers of the epidermis are named forthese characteristic traits :

    Basal layer, Spinous layer, Granular layerand Stratum Corneum

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    The Keratinocyte

    As keratinocytes migrate through thelayers of the epidermis, their contents andfunctions change according to or

    depending on the specific epidermal layerin which they are moving

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    The Basal Layer

    Located at the base of the epidermis

    Basal Cells are cuboidal in shape

    Produced by stem cells

    When the stem cells divide, they createdaughter cells, which is slowly move to the top

    of epidermis

    Basal cells join with other basal calledHemidesmosome and overlying spinous cells viaDesmosomes to form the basement membrane

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    The Basal Layer

    These basal keratinocytes containkeratines 5 and 14, mutations that result inan inherited disease called epidermolysis

    bullosa.

    Responsible for maintaining the epidermisby continually renewing the cell

    population.

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    The Basal Layer

    10 percent of cells are stem cells, 50 percent areamplifyng cells, and 40 percent are postmitoticcells that move superficiallysuperbasal cells.

    It is worth noting that basal cells produce bullouspemphigoid antigens, which are proteins thatlead to the development of bullous pemphigoiddisease, if the body produces corresponding

    antibodies.

    Contains melanocytes that produce melanin

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    The Spinous Layer

    Have prominent spiny attachments calleddesmosomes.

    Keratins 1 and 10 are first seen in thislayer of suprabasal keratinocytes.

    This keratins form a more rigidcytoskleleton that provides a greatermechanical strength to the cell.

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    The Spinous Layer

    Lamellar granules- which are considered thefirst sign of keratinization- first appear in this

    layer. These granules contain lipids such as

    ceramides, cholesterol, and fatty acids, as well

    as enzymes such as proteases, acidphosphatase, lipases, and glycosidases.

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    The Spinous Layer

    Lamellar granules migrate to the surfaceand expel their contents by exocytosis.

    The lipids that are released coat thesurface to provide barrier-like properties.

    Desmosomes are very prominent in thislayer, thus accounting for the namespinous layer.

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    The Granular Layer

    Contain visible keratohyaline granules.

    The uppermost viable layer of theepidermis.

    The granules represent keratohyalinegranules, which contain profilaggrin, theprecursor to fillagrin.

    Filaggrin cross-links keratin filaments,providing strength and structure.

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    The Horny Layer / SC

    Stratum corneum, a condensed mass of cellsthat have lost their nuclei and granules.

    Covered by cell envelope, which aids in

    providing a barrier to water loss and absorptionof unwanted materials.

    The Corneocytes that reside in this layer are themost mature and have completed thekeratinization process.

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    The Horny Layer

    These Corneocytes have no organelles, andtheir arrangement resembles a brick wall.

    Composed of protein-rich corneocytes

    embedded in a bilayer lipid matrix arranged in abrick and mortar fashion.

    The bricks are composed of corneocytes, andthe mortar is composed of the contents

    extruded from the lamellar granules, includinglipids and proteins.

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    The Horny Layer

    The stratum corneum is described as the dead

    layer of cellsdo not demonstrate proteinsynthesis and unresponsive to cellular signaling.

    The function : protective barrier to preventtransepidermal water loss (TEWL).

    Amino acids and their metabolites, which byproducts formed from the breakdown of filaggrin,make up a substance known as the naturalmoisturizing factor (NMF).

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    The Horny Layer

    NMF and lipids released by the lamellargranules play an important role in skinhydration, suppleness, and flexibility.

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    The Cell Cycle

    The above keratinization process is also referredto as the cell cycle.

    Normal cell cycle of the epidermis : 26- 42 days.

    = desquamation, normally occurs invisibly withshedding of individual cells or small clumps ofcells.

    Disturbances of this processaccumulation of

    partially detached keratinocytes clinicalfindings of dry skin

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    The Cell Cycle

    Disease states may also after the cell cycle. Forexample, psoriasis dramatic shortening of thecell cycle formation of crusty cutaneouseruptions.

    In aging : cell cycle lengthens in time cells atthe superficial layer of the stratum corneum (SC)are older and their function may be empaired.

    Many cosmetic products such as retinol and -

    hydroxy acids are believed to quicken the paceof the cell cycle, leading to youngerkeratinocytes at the superficial layers of SC.

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    Moisturization of the StratumCorneum

    A main function of the SC is to preventTEWL by regulating the water balance inthe skin.

    Two major components : lipids and theNMF.

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    Natural Moisturizing Factor

    Released by thelamellar granules, NMF is composedof amino acids and their metabolits productsformed from the breakdown of filaggrin.

    NMF found exclusively inside the cells of SC givesSC its humectant (water-binding) qualities. NMF is made of very water-soluble chemicals can

    absorb amounts of water, even when humidity levelsare low enable SC to retain a high water contenteven in a dry environment.

    The NMF also provides an important aqueousenvironment for enzymes that need such anenvironment to function.

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    Natural Moisturizing Factor

    The importance of NMF is clear when one notes thatichthyosis vulgaris patients, who lack NMF,demonstrate severe dryness and scaling of the skin.

    Normal skin that is exposed to normal soap washinghas significantly lower levels of NMF when comparedto normal skin not washed with surfactants.

    Levels of NMF also decline with age increasedincidence of dry skin in the elderly population.

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    Lipids

    In order of abundance, the composition of skinsurface lipids includes triglycerides, fatty acids,squalene, wax esters, diglycerides, cholesterol

    esters, and cholesterol. Important part of the epidermis and are involved

    in preventing TEWL and the entry of harmfulbacteria.

    Prevent the skin from absorbing water-solubleagents.

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    Lipids

    For decades it has been known that theabsence of lipids in the diet leads tounhealthy skin.

    Inherited defects in lipid metabolism, suchas the deficiency of steroid sulfatase seenin X-linked ichthyosis abnormal skinkeratinization and hydration.

    Stratum corneum lipids are affected byage, genetics, seasonal variation, and diet.

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    Lipids

    Deficiency of these lipids predisposes theindividual to dry skin. This wasdemonstrated in mice with essential fatty

    acids deficiency (EFAD) that, when fed adiet deficient in linoleic acid, developedincreased TEWL. Interestingly,

    administration of hypocholesterolemicdrug is also associated with dry skinchanges.

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    Lipids

    Skin lipids are produced in and extruded from lamellargranules as described above, or are produced insebaceous glands and then excreted to the skins

    surface through the hair follicle.

    The excretion of sebum by sebaceous glands ishormonally controlled.

    Lipids help keep the NMF inside the cells keep cellshydranated and aqueous enzymes.

    Lipids can influence enzyme function.

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    Role of Lipids in TEWL

    The major lipids found in the SC that contributeto the water permeability barrier are ceramides,cholesterol, and fatty acids.

    Since 1940s, when the stratum corneum wasfirst identified as the important barrier to waterloss, many hypotheses have been entertainedas to exactly which lipids are important in theSC.

    The research with the EFAD mice describedabove led many to focus on phosphelipidsbecause they contain linoleic acids.

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    Role of Lipids in TEWL

    However, it was later found that phospholipidsare almost completely absent from the SC.

    In 1982, ceramide 1 discovered. This lipid

    compound is rich in linoleic acid

    play a majorrole in structuring SC lipids essential for barrierfunction. Later five more distinct types ofceramides were discovered and namedaccording to the polarity of the molecule.

    Ceramide 1 is the most nonpolar and ceramide6 is the most polar.

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    Role of Lipids in TEWL

    Although the ceramides were once thought to bethe key to skin moisturization, studies nowsuggest that no lipid is more important than any

    other lipid. The most important parameter : ratio of fatty

    acid, ceramides, and cholesterol. This isdemonstrated in a study that showed that after

    altering the water barrier with acetone, theapplication of ceramides, fatty acids, andcholesterol resulted in normal barrier recovery.

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    Role of Lipids in TEWL

    Application of each of the separate entitiesalone resulted in delayed barrier recovery.

    Many products on the market containceramides or a mixture of ceramides,cholesterol, and fatty acids. However, theuse of these mixtures to treat atopic

    dermatitis and other ichthyotic disordershas been disappointing.

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    Summary

    The epidermis is implicated in many of the skincomplaints of cosmetic patients. It is the state of theepidermis that causes skin to feel rough and appear

    dull. A flexible, well-hydrated epidermis more supple and

    radiant than a dehydrated epidermis.

    The popularity of buff puffs, exfoliating scrubs,masks, moisturizers, chemical peels,microdermabrasion attests to the obsession thatcosmetic patients have with condition of theirepidermis

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    Summary

    It is important to understand the propertiesof the epidermis in order to understandwhich cosmetic products and procedures

    can truly benefit patients as opposed tothose that are based on myth or hype.

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    BASIC SCIENCE OF THE DERMIS

    The dermis lies between the epidermisand the subcutaneous fat responsiblefor the thickness of the skin cosmetic

    appearance.

    The thickness of the dermis varies overdifferent parts of the body and doubles

    between the ages of three and sevenyears old and again at puberty.

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    BASIC SCIENCE OF THE DERMIS

    With aging decreases in thickness andmoisture.

    The dermis, which is laden with nerves,blood vessels, and sweat glands, consistsmostly of collagen.

    The uppermost portion of this layerlies

    beneath the epidermispapillary dermis

    The lower portion the reticular dermis.

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    BASIC SCIENCE OF THE DERMIS

    Smaller collagen bundles, greater cellularity,and a higher density in its vascular

    elements characterize the papillary dermisas compared to the reticular dermis.

    Fibroblasts the primary cell type in the

    dermis

    produce collagen, elastin, othermatrix proteins, and enzymes such ascollagenase and stromelysin.

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    BASIC SCIENCE OF THE DERMIS

    Immune cells such as mast cells,Langerhans cell , polymorphonuclearleukocytes (PMNs), lymphocytes, and

    macrophages are also present in thedermis.

    Junction epidermis - dermis -->dermal-epidermal junction (DEJ).

    Attachment proteins found in thebasement membrane of the DEJ.

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    Collagen

    One of the strongest natural proteins durability &resilience characteristics of skin.

    The focus of much anti aging research and the targetof many skin products and procedures.

    The importance of collagen is emphasized in theliterature regarding many of the topical agents that

    claim to increase collagen syntheses, such as glycolicacid and ascorbic acid.

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    Collagen

    Resurfacing techniques (CO2 laser anddermabrasion) change collagenstructureimproving skin texture.

    Various forms of collagen are injected intothe dermis to replace damaged collagenand to reverse the signs of aging.

    Topical retinoids reduce the collagendamage that occurs due to sun exposure.

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    Collagen

    A complex family of 18 proteins, 11 dermis.

    Always seen in the final, mature, state of

    assembly as opposed to elastin, whoseimmature fibers are seen in the superficialdermis and whose more mature fibers arefound in the deeper layer of dermis.

    Each type of collagen is composed of threechains.

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    Collagen Collagen is synthesized in the fibroblastsin a precursor form called procollagen.

    TYPES of Collagen in Dermis :

    - Type 1 : 80 -85% of dermal matrix

    responsible for the tensilestrength of dermis

    in photoaged skin

    after dermabrasion

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    Collagen

    Types of Collagen :

    - Type III : 10-15% of dermal matrix

    smaller than type I

    skinpliability

    fetal collagen

    predominates in embryonic life around blood vessels &beneath epidermis

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    Collagen

    Types of Collagen :

    - Type IV : forms a structure lattice in thebasement zone

    - Type V : 4-5% dermal matrix

    - Type VII : makes up the anchoring fibrilsin the DEJ

    - Type XVII : in the hemidesmosome

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    Collagen

    Types of Collagen :Important in genetic diseases

    Ex : Scarcity of type VII abnormalities in

    anchoring fibrils Dominant DystrophicEpidermolysis

    Antibody to Type VII Epidermolysis

    Bullosa Acquisita (EBA)Loss of anchoring fibrils (Type VII)

    weakened bond dermis-epidermis wrinkle

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    ELASTIN

    Found at the periphery of collagen bundles

    & endow the skin with recoil properties

    Assembled on bundles of microfibrils composed offibrillin

    Fibrillin forms a template deposited of elastin

    Sun exposure elastin degrades amorphoussubstance in dermisELASTOSIS (hallmark ofphotoaged skin)

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    Elastin

    Damage to elastin fibers decreasedskin elasticity

    Defect / damage to elastin wrinkles

    WRINKLED SKIN SYNDROME childwith deficiency of elastin fibers

    Elastin fibers present in various levels ofmaturity.

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    Glycoproteins (GP)

    influence cell migration, adhesion &orientation

    Fibronectin & Tenascin most relevantGPs in dermis

    Fibronectin : filamentous GP mediatesplatelet binding to collagen, development

    of granulation tissue & reepithelialization

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    Glycoprotein

    Tenascin : found only in the papillarydermis in adult skin significant role intissue remodelling & important in wound

    healing following cosmetic procedures

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    Glycosaminoglycans (GAGs)

    polysaccharide chains composed ofrepeating disaccharide units -> linked to acore protein

    Bind water avidly maintenance of salt &water balance

    Found in areas with a fibrous matrix

    cells are closely associated but have littlespace for free movement

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    Glycosaminoglycans (GAGs)

    The most abundant GAGs in dermis :Hyaluronic acid (HA) and dermatan sulfate

    HA : - important in cell growth, membrane

    receptor function & in adhesion- appears freely in dermis :Young skin : periphery of collagen &

    elastin fibers & at interface of thesefibers

    Aged skin : no connection-Popular in cosmetic products humectant

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    Hypodermis

    Hypodermis = Subcutis

    Located beneath dermis

    Composed : Fat (mostly) importantenergy source for the body

    Contains : collagens type I, III,V

    Aged skin : subcutaneous fat is lost orredistributed into undesired area

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    SUMMARY

    Epidermis is the target of most topicalcosmetic products

    Dermis is the target for injectable

    treatment for aging

    Dermis is an extremely importantcomponent in skin appearance

    responsible for giving skin thickness &suppleness

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    SUMMARY

    Thinner dermis & altered junction betweenepidermis dermis hallmarks of agedskin

    Loss of collagen, elastin & GAGs locatedprimarily in the dermis cutaneous aging