Anatomy & Physiology

of

The Skin

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Basic Science of the Epidermis

The skin is composed of the 3 primary layers: Epidermis, Dermis & Subcutaneous Each layer specific characteristics & functions The Epidermis ->most superficial layer plays important role from a cosmetic standpoint gives the skins texture, moisturize and color
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Basic Science of the Epidermis

Knowledge of the basic structure of the Epidermis best enables a practitioner to improve the appearance of patients skin In the future, study of these components is likely to lead to an enhanced understanding of skin aging and the effects of topical products on the biological function of the skin
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The Keratinocyte
Also known as corneocytes Born at the base of the epidermis at the dermal-epidermal junction / DEJ Produced by stem-cells, and slowly move to the top These process of cells maturing and moving to the top is called keratinization
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The Keratinocyte
As the cells move through the epidermis and mature, they develop different characteristics The layers of the epidermis are named for these characteristic traits : Basal layer, Spinous layer, Granular layer and Stratum Corneum

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The Keratinocyte
As keratinocytes migrate through the layers of the epidermis, their contents and functions change according to or depending on the specific epidermal layer in 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 create daughter cells, which is slowly move to the top of epidermis Basal cells join with other basal called Hemidesmosome and overlying spinous cells via Desmosomes to form the basement membrane
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The Basal Layer

These basal keratinocytes contain keratines 5 and 14, mutations that result in an inherited disease called epidermolysis bullosa. Responsible for maintaining the epidermis by continually renewing the cell population.

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The Basal Layer

10 percent of cells are stem cells, 50 percent are amplifyng cells, and 40 percent are postmitotic cells that move superficially superbasal cells. It is worth noting that basal cells produce bullous pemphigoid antigens, which are proteins that lead to the development of bullous pemphigoid disease, if the body produces corresponding antibodies. Contains melanocytes that produce melanin
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The Spinous Layer

Have prominent spiny attachments called desmosomes. Keratins 1 and 10 are first seen in this layer of suprabasal keratinocytes. This keratins form a more rigid cytoskleleton that provides a greater mechanical strength to the cell.

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The Spinous Layer

Lamellar granules- which are considered the first 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, acid phosphatase, lipases, and glycosidases.
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The Spinous Layer

Lamellar granules migrate to the surface and expel their contents by exocytosis. The lipids that are released coat the surface to provide barrier-like properties. Desmosomes are very prominent in this layer, thus accounting for the name spinous layer.

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The Granular Layer

Contain visible keratohyaline granules. The uppermost viable layer of the epidermis. The granules represent keratohyaline granules, which contain profilaggrin, the precursor 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 cells that have lost their nuclei and granules. Covered by cell envelope, which aids in providing a barrier to water loss and absorption of unwanted materials. The Corneocytes that reside in this layer are the most mature and have completed the keratinization process.

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The Horny Layer

These Corneocytes have no organelles, and their arrangement resembles a brick wall. Composed of protein-rich corneocytes embedded in a bilayer lipid matrix arranged in a brick and mortar fashion. The bricks are composed of corneocytes, and the mortar is composed of the contents extruded from the lamellar granules, including lipids and proteins.
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The Horny Layer

The stratum corneum is described as the dead layer of cells do not demonstrate protein synthesis and unresponsive to cellular signaling. The function : protective barrier to prevent transepidermal water loss (TEWL). Amino acids and their metabolites, which by products formed from the breakdown of filaggrin, make up a substance known as the natural moisturizing factor (NMF).
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The Horny Layer

NMF and lipids released by the lamellar granules play an important role in skin hydration, suppleness, and flexibility.

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The Cell Cycle

The above keratinization process is also referred to as the cell cycle. Normal cell cycle of the epidermis : 26- 42 days. = desquamation, normally occurs invisibly with shedding of individual cells or small clumps of cells. Disturbances of this process accumulation of partially detached keratinocytes clinical findings of dry skin

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The Cell Cycle

Disease states may also after the cell cycle. For example, psoriasis dramatic shortening of the cell cycle formation of crusty cutaneous eruptions. In aging : cell cycle lengthens in time cells at the 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 pace of the cell cycle, leading to younger keratinocytes at the superficial layers of SC.
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Moisturization of the Stratum Corneum

A main function of the SC is to prevent TEWL by regulating the water balance in the skin. Two major components : lipids and the NMF.

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Natural Moisturizing Factor

Released by thelamellar granules, NMF is composed of amino acids and their metabolits products formed from the breakdown of filaggrin. NMF found exclusively inside the cells of SC gives SC its humectant (water-binding) qualities. NMF is made of very water-soluble chemicals can absorb amounts of water, even when humidity levels are low enable SC to retain a high water content even in a dry environment. The NMF also provides an important aqueous environment for enzymes that need such an environment to function.
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Natural Moisturizing Factor

The importance of NMF is clear when one notes that ichthyosis vulgaris patients, who lack NMF, demonstrate severe dryness and scaling of the skin. Normal skin that is exposed to normal soap washing has significantly lower levels of NMF when compared to normal skin not washed with surfactants. Levels of NMF also decline with age increased incidence of dry skin in the elderly population.
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Lipids
In order of abundance, the composition of skin surface 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 harmful bacteria. Prevent the skin from absorbing water-soluble agents.
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Lipids
For decades it has been known that the absence of lipids in the diet leads to unhealthy skin. Inherited defects in lipid metabolism, such as the deficiency of steroid sulfatase seen in X-linked ichthyosis abnormal skin keratinization and hydration. Stratum corneum lipids are affected by age, genetics, seasonal variation, and diet.
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Lipids
Deficiency of these lipids predisposes the individual to dry skin. This was demonstrated in mice with essential fatty acids deficiency (EFAD) that, when fed a diet deficient in linoleic acid, developed increased TEWL. Interestingly, administration of hypocholesterolemic drug is also associated with dry skin changes.
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Lipids
Skin lipids are produced in and extruded from lamellar granules as described above, or are produced in sebaceous glands and then excreted to the skins surface through the hair follicle. The excretion of sebum by sebaceous glands is hormonally controlled. Lipids help keep the NMF inside the cells keep cells hydranated 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 contribute to the water permeability barrier are ceramides, cholesterol, and fatty acids. Since 1940s, when the stratum corneum was first identified as the important barrier to water loss, many hypotheses have been entertained as to exactly which lipids are important in the SC. The research with the EFAD mice described above led many to focus on phosphelipids because they contain linoleic acids.
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Role of Lipids in TEWL

However, it was later found that phospholipids are almost completely absent from the SC. In 1982, ceramide 1 discovered. This lipid compound is rich in linoleic acid play a major role in structuring SC lipids essential for barrier function. Later five more distinct types of ceramides were discovered and named according to the polarity of the molecule. Ceramide 1 is the most nonpolar and ceramide 6 is the most polar.
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Role of Lipids in TEWL

Although the ceramides were once thought to be the key to skin moisturization, studies now suggest that no lipid is more important than any other lipid. The most important parameter : ratio of fatty acid, ceramides, and cholesterol. This is demonstrated in a study that showed that after altering the water barrier with acetone, the application of ceramides, fatty acids, and cholesterol resulted in normal barrier recovery.
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Role of Lipids in TEWL

Application of each of the separate entities alone resulted in delayed barrier recovery. Many products on the market contain ceramides or a mixture of ceramides, cholesterol, and fatty acids. However, the use of these mixtures to treat atopic dermatitis and other ichthyotic disorders has been disappointing.
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Summary
The epidermis is implicated in many of the skin complaints of cosmetic patients. It is the state of the epidermis 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 that cosmetic patients have with condition of their epidermis
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Summary
It is important to understand the properties of the epidermis in order to understand which cosmetic products and procedures can truly benefit patients as opposed to those that are based on myth or hype.

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BASIC SCIENCE OF THE DERMIS

The dermis lies between the epidermis and the subcutaneous fat responsible for the thickness of the skin cosmetic appearance. The thickness of the dermis varies over different parts of the body and doubles between the ages of three and seven years old and again at puberty.
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BASIC SCIENCE OF THE DERMIS

With aging decreases in thickness and moisture. The dermis, which is laden with nerves, blood vessels, and sweat glands, consists mostly of collagen. The uppermost portion of this layer lies beneath the epidermis papillary 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 dermis as compared to the reticular dermis. Fibroblasts the primary cell type in the dermis produce collagen, elastin, other matrix proteins, and enzymes such as collagenase and stromelysin.
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BASIC SCIENCE OF THE DERMIS

Immune cells such as mast cells, Langerhans cell , polymorphonuclear leukocytes (PMNs), lymphocytes, and macrophages are also present in the dermis. Junction epidermis - dermis --> dermal-epidermal junction (DEJ). Attachment proteins found in the basement 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 target of many skin products and procedures. The importance of collagen is emphasized in the literature regarding many of the topical agents that claim to increase collagen syntheses, such as glycolic acid and ascorbic acid.
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Collagen
Resurfacing techniques (CO2 laser and dermabrasion) change collagen structure improving skin texture. Various forms of collagen are injected into the dermis to replace damaged collagen and to reverse the signs of aging. Topical retinoids reduce the collagen damage 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, whose immature fibers are seen in the superficial dermis and whose more mature fibers are found in the deeper layer of dermis. Each type of collagen is composed of three chains.
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 Collagen is synthesized in the fibroblasts in a precursor form called procollagen. TYPES of Collagen in Dermis : - Type 1 : 80 -85% of dermal matrix responsible for the tensile strength of dermis in photoaged skin after dermabrasion
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Collagen

Collagen
Types of Collagen : - Type III : 10-15% of dermal matrix smaller than type I skin pliability 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 the basement zone - Type V : 4-5% dermal matrix - Type VII : makes up the anchoring fibrils in 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 Dystrophic Epidermolysis 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 of fibrillin Fibrillin forms a template deposited of elastin Sun exposure elastin degrades amorphous substance in dermis ELASTOSIS (hallmark of photoaged skin)
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Elastin
Damage to elastin fibers decreased skin elasticity Defect / damage to elastin wrinkles WRINKLED SKIN SYNDROME child with deficiency of elastin fibers Elastin fibers present in various levels of maturity.
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Glycoproteins (GP)
influence cell migration, adhesion & orientation Fibronectin & Tenascin most relevant GPs in dermis Fibronectin : filamentous GP mediates platelet binding to collagen, development of granulation tissue & reepithelialization

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Glycoprotein
Tenascin : found only in the papillary dermis in adult skin significant role in tissue remodelling & important in wound healing following cosmetic procedures

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Glycosaminoglycans (GAGs)
polysaccharide chains composed of repeating disaccharide units -> linked to a core protein Bind water avidly maintenance of salt & water balance Found in areas with a fibrous matrix cells are closely associated but have little space 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 these fibers Aged skin : no connection -Popular in cosmetic products humectant
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Hypodermis
Hypodermis = Subcutis Located beneath dermis Composed : Fat (mostly) important energy source for the body Contains : collagens type I, III,V Aged skin : subcutaneous fat is lost or redistributed into undesired area
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SUMMARY
Epidermis is the target of most topical cosmetic products Dermis is the target for injectable treatment for aging Dermis is an extremely important component in skin appearance responsible for giving skin thickness & suppleness
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SUMMARY
Thinner dermis & altered junction between epidermis dermis hallmarks of aged skin Loss of collagen, elastin & GAGs located primarily in the dermis cutaneous aging

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