Beginers skin histology workbook v1 21218

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SCIENCE OF SKIN HEALTH Understanding Skin Histology

This document is strictly private, confidential and personal to its recipients and should not be copied, distributed or reproduced in whole or in part, nor passed to any third party.


LEARNING TRACK BEGINNERS

Science of Skin Health Understanding Skin Histology ZO® Skin Health product are designed to target a variety of different skin structures. This course has been designed to provide a basic overview of skin structures and their functions so that you develop a better understanding of how our products work to deliver innovative skin care solutions to optimize skin health restoration.

Supporting Workbooks ▪

ZO® AT-A GLANCE PRODUCT GUIDE

ZO® SKIN HEALTH RESTORATION PROGRAMS (Protocols)

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TABLE OF CONTENTS

Understanding Skin Histology

P.04

Epidermis

P.06

Dermis

P.17

Essential Topical Agents

P.31

ZO® Principles of Skin Health Restoration

P.34

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Skin Histology

SKIN ▪ Largest organ of the body ▪ Makes up approximately 15-18% of our body weight ▪ Skin undergoes numerous changes ▪ Adapting to the environment

The Skin is the largest organ of the body. The surface area is roughly 1.8m2, which equates to 6 ft2, and makes up approximately 15-18% of our body weight. During our lifetime, our skin undergoes numerous ch anges, including adapting to the change from a water environment while in the womb to an air environment at birth. The skin adapts to hormonal influences at puberty. In females, the skin adjusts for the effects of h ormonal changes.

FUNCTION Much like a suit of amour, our skin is a form of protection for our inner organs. This amour provides our skin a barrier that prevents invasion from irritants and bacteria such as Staphylococci, which is often found on o ur skin or in our nose and usually don’t cause problems. This bacteria may lead to minor skin infections, such as boils and impetigo. This barrier makes us waterproof from the inside out and offers protection from UV radiation.

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Skin Histology

Skin divided into 3 sections: Epidermis Dermis Subcutaneous layers What do we find within the Dermis? Hair follicle, arrector pili muscle, sebaceous gland, eccrine and apocrine sweat glands, nerve endings, blood capillaries, lymphatic vessels. All supported by the ground substance, a jelly like fluid that provides support and plumpness to the skin. Contains Collagen (approx 80%) and Elastin fibers, (3%)* Hyaluronic acid * Heparin and Dermatan Sulfate .(*Glycosaminoglycans) - many sticky sugars – protein chains. The Dermis is split into 2 main sections, top part where the papilla of the hair follicle projects up into the Basal layer, causing the wave effect known as the Papillary layer. Lower down is the Reticular layer where the predominance of fibers lie. It is important to understand how the skin reacts when touched or treated, manually, electrically or with product.

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Skin Histology

Epidermis

The epidermis is the outermost layer of our skin. It is the thinnest layer, and forms the barrier of protection from the outside world.

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Skin Histology

EPIDERMIS The stratum basale is a single layer of cells primarily made of basal cells. A basal cell is a precursor of the keratinocytes of the epidermis. All of the keratinocytes are produced from this single layer of cells, which are constantly going through mitosis to produce new cells. As new cells are formed, the existing cells are pushed superficially away from the stratum basale.. The stratum granulosum has a grainy appearance due to further changes to the keratinocytes as they are pushed from the stratum spinosum. The cells (three to five layers deep) become flatter, their cell membranes thicken, and they generate large amounts of the proteins keratin, which is fibrous, and keratohyalin, which accumulates as lamellar granules within the cells. These two proteins make up the bulk of the keratinocyte mass in the stratum granulosum and give the layer its grainy appearance. The nuclei and other cell organelles disintegrate as the cells die, leaving behind the keratin, keratohyalin, and cell membranes that will form the stratum lucidum, the stratum corneum, and the accessory structures of hair and nails. The stratum lucidum is a smooth, seemingly translucent layer of the epidermis located just above the stratum granulosum and below the stratum corneum. This thin layer of cells is found only in the thick skin of the palms, soles, and digits. The keratinocytes that compose the stratum lucidum are dead and flattened. These cells are densely packed with eleiden, a clear protein rich in lipids, derived from keratohyalin, which gives these cells their transparent (i.e., lucid) appearance and provides a barrier to water, which we see through the wrinkling of our fingers and toes when we bathe. The stratum corneum is the most superficial layer of the epidermis and is the layer exposed to the outside environment. The cells found in this layer are now considered corneocytes as a result of the increased keratinization (also called cornification) of the cells in this layer. There are usually 15 to 20 layers of cells in the stratum corneum. Each corneocyte is surrounded by a protein envelope and is filled with waterretaining keratin proteins. The cellular shape and orientation of the keratin proteins add strength to the stratum corneum. Surrounding the cells in the extracellular space are stacked layers of lipid bilayers. The resulting structure provides the natural physical and water-retaining barrier of the skin. Cells in this layer are shed periodically and are replaced by cells pushed up from the stratum granulosum (or stratum lucidum in the case of the palms and soles of feet).

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Skin Histology

4.

Keratohyalin (fillagrin) starts to fill the cell, organelles breakdown

3.

Lamellar bodies excrete lipids, into the intercellular spaces to make lamellae

2.

Desmosomes and keratin tonafilaments present

1.

Cell birth, division and differentiation

There are actually 2 major developments that take place in the skin: • Keratin synthesis • Lipid synthesis

KERATINIZATION The epidermis is a multi-layered structure that is continually renewing itself from the deepest layer known as the Stratum Germinativum or basal cell layer. After cells are “born” in the basal cell layer they migrate to the skin surface, undergoing a process called keratinization whereby the structure and chemical composition of the cells changes.

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Skin Histology

KERATINIZATION The cells are born in the Stratum Germinativum. They are columnar in shape and actively divide, half of these cells progress upwards and differentiate, while the other half remain behind to divide again. The dividing basal cell, on average, replicates every 200-400 hours and the resulting cell takes 14 days to differentiate and 14 days to be shed. Keratin filaments begin in this early stage, they are part of the inner cell and cytoplasm which changes as the cells moves through the layers. Hemidesmosomes attach the cells of this layer to the basement membrane that separates the epidermis from the loose connective tissue of the adjacent dermis in the prickle cell layer (Stratum Spinosum), the shape of cells change from columnar to polygonal. The prickle cell layer or Stratum Spinosum gets its name because of the appearance of spine-like protrusions that occur when these cells shrink back under observation. The spines occur where there are desmosomes or adhesion points between cells. Spinosum cells each have characteristically large bundles of keratin filaments (tonofilaments) organized around the nucleus of the cell extending to the desmosomes on the outer membrane of the cell. The granular layer (Stratum Granulosum) is the transitional zone as it is here that we see more flattened cells containing numerous particles known as keratohyaline granules (made of a protein called fillagrin). Keratohyaline is important as it starts to fill the cells, it isn’t because the cell is filled with keratin that it is dead but because the destruction of the nucleus and other organelles is accelerated and completed in the Stratum Corneum. Also present in the cytoplasm of cells around the periphery of the cell membrane are organelles known as lamellar bodies or granules. They are lipid structures, containing fatty acids, ceramides, cholesterol and enzymes. They discharge their contents into the intercellular spaces between the cells of the granular layer and Stratum Corneum, providing what is referred to as lamellae and this is what makes up the skin’s lipid barrier to prevent water loss and invasion. Water is also trapped between these lipids to contribute to the NMF. In the horny layer (Stratum Corneum), the dead flattened corneocytes have developed to thickened cell envelopes enclosing a matrix of keratin tonofilaments. Corneocytes are shed from the skin surface. The Stratum Dysjunctum is the outer few ‘shell’ layers of dead epidermal cells. This is the layer we normally exfoliate. When we exfoliate and remove dead cells, automatically then new cells are born and pushed upwards. (Skin is homeostatic and knows when to produce more cells, think about when we have a pressure spot and the skin makes a corn to protect itself). Skin exfoliation and skin renewal go hand-in-hand. This keeps the epidermis at the same thickness all the time at least in a healthy skin! Although it is considered a dead cell, do not mistake this for a non-functioning entity; the Stratum Corneum cells are fully functional, particularly in terms of providing barrier properties for the Stratum Corneum.

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Skin Histology

DESQUAMATION What we know about desquamation Desmosomes that link or bridge the cells are broken down by skin enzymes (Stratum Corneum chymotryptic enzyme.) Lamellar bodies (also known as Odland Bodies) or granules secrete their LIPID contents into the intercellular space in the Stratum Corneum, the enzyme cholesterol sulfatase (a microsomal enzyme that breaks down the sulfate group from sulfated sterols) modifies the lipids, which assists, not only in, proper hydration of the epidermis, but in the desquamation process itself. The absence of this enzyme in the lamellar bodies or granules corresponds with a failure of the Stratum Corneum cells to slough - a condition known as retention hyperkeratosis (problem with acne and other proliferative skin disorders). Stratum Corneum Chymotypic are the enzymes involved in desquamation. As to be expected, younger skin is more efficient at this process of desquamation which stimulates the growth of newer cells at a deeper level. As we age the glue-like intercellular cement holding the cells together becomes denser, causing a build-up in the layers of cells; cell sloughing becomes more difficult resulting in a skin that appears dull, thicker and with less tone. This may be exacerbated by environmental factors (exposure to sunlight), hormonal influences (androgens, estrogens and epidermal growth factor) and deficiencies in various Vitamins (A and D). With all of these influences affecting the desquamation process it is apparent why exfoliation is so important to the skin. Removing this build-up of dead, damaged skin cells stimulates the regeneration of new cells improving the skin’s appearance, feel and texture. Lamellar granules or bodies / membrane-coating granules / keratinosomes / cementosomes / Odlandbodies: one of the spherical granules that are formed in the upper spinous and granular layers of the skin near the Golgi apparatus and migrate into the cytoplasm, ultimately fusing with the plasma membrane to discharge their contents (bipolar phospholipids, glycoproteins and acid phosphates) into the intercellular space; this extruded material is thought to function as a barrier to penetration by foreign substances. Can be affected by the environment:: age, UV exposure, hormones, vitamin deficiencies and exfoliation

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Skin Histology

KERATINOCYTE MATURITY CYCLE ▪ Essential for naturally hydrated and tolerant skin ▪ KMC cycles restores skin barrier function leading

Skin’s normal barrier function is dependent upon a healthy epidermal renewal cycle. The KMC is the foundation of Skin Health Restoration because without adequate epidermal exfoliation and subsequent replacement with fresh, active cells, skin health is compromised. Keratinocyte Maturation Cycles are essential for naturally hydrated and tolerant skin. The restoration of Keratinocyte Maturation Cycles restores skin barrier function leading to increases in skin tolerance. Keratinocyte Maturation Cycle 4-6 Weeks Benefits include: ▪ Smooth, soft skin surface ▪ Thicker epidermis ▪ Proper hydration ▪ Uniform skin tone

Corneocytes Mature Keratinocytes

Keratinocytes

Basal Cells

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Skin Histology

BARRIER FUNCTION â–Ş NMF formed by Amino Acids from fillagrin, sweat and sebum secretions â–Ş Lipid Membranes from the lamellar granule lipids and sebaceous gland

One of the protective functions of the Stratum Corneum is to prevent dehydration of the skin by reducing Trans Epidermal Water Loss (TEWL). The 2 major components of the Stratum Corneum that allow it to perform this function are the Natural Moisturizing Factor (NMF) and lipid membrane. The NMF is the result of a combination of amino acids and breakdown products of fillagrin combined with secretions from the sweat and sebaceous glands (including urea, salts and organic acids). NMF has the ability to hold large amounts of water in the skin. It also provides an important aqueous environment for enzymes of the Stratum Coreneum. The skin also contains lipids to control TEWL. Skin lipids are produced in and extruded from lamellar granules or are produced and excreted from the sebaceous glands associated with the hair follicle. The major lipids that help control TEWL are ceramides, cholesterol and fatty acids. Not only do these lipids control TEWL, but they prevent the entry of water-soluble environmental agents and harmful bacteria into the skin. The lipids of the Stratum Corneum are effected by age, genetics, seasonal influences and diet. Any deficiency in these lipids results in dry skin due to increased TEWL.

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Skin Histology

MELANOCYTE ▪ ▪ ▪ ▪ ▪

Responsible for the production of melanin One melanocyte provides melanin to 36 Keratinocytes Structure consists of a cell body and spiny like protrusions called Dendrites Minute grains of pigment contained within a membrane Delivered in a “syringe” type of process from the Dendrites to the Keratinocytes

Melanosomes are tiny grains of pigment-like ink. Formed by the Golgi apparatus (a collection of membr anes that store and deliver protein enzymes). Color depends on the distribution of these grains throughout the epidermis, not the quantity of the melanocytes found in the skin. Syringe type of delivery It takes 14-20 days for melanin to reach the Stratum Corneum. There are 4 stages of maturation before melanosomes reach the keratinocyte. Deterioration then begins as the keratinocyte starts on its transition up through the epidermis, the melanosomes are digested by the keratinocyte.

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Skin Histology

MELANOCYTE The production of melanin by the melanocyte is a complicated conversion which is "triggered" by a key amino acid known as Tyrosine. The molecular changes and the maturation of melanin is referred to as melanogenesis. It is the biosynthesis of melanin, or the changes that take place on this level, that will result in pigmentation. The melanin produced undergoes a maturing process before moving into the keratinocyte. There are many chemical changes that take place and involve some co-factors to be present to allow for the synthesis of melanin. These transitions and chemical changes that take place are numerous but tyrosinase plays the largest role. Tyrosine is converted to L-Dopa (DihydrOxyPhenylAlanine) by Tyrosinase. The process continues with L- Dopa (L-Dopa is a Dihydroxybenzene derivative - important later) being converted to L-Dopa Quinone (loss of 2 hydrogen molecules and the presence of Copper, Copper is required as an enzyme co-factor). At this stage, the pathway splits to form either Eumelanin or Pheomelanin (Cysteine a Sulphur compound needs to be present but oxidizes readily, genes also play a large role in this process). Most of us have a combination of both types and this is determined by our genes. Neuromelanin Primarily found in the areas of the central nervous system such as the brain stem, nerve roots, mucus membranes, inner ear and gastrointestinal tract. Eumelanin This is a brown/black pigment that we find in Caucasian, Asian and ethnic skin. This is the most common pigment that we see in the skin. The content and intensity of this pigment will give indication of the degree of photo-protection. Pheomelanin This is the yellow/red pigment that we see in fair skin and red hair. It is synthesized from Tyrosine and Cystine which means it is less stable to ultraviolet light. The result is that this pigment oxidizes, which explains why red hair is relatively rare. This type of melanin offers no photo protection. Tyrosinase is a Copper containing enzyme that catalyzes 2 distinct reactions in the production of melanin.

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Skin Histology

LANGERHANS CELLS ▪ Found in the Stratum Spinosum ▪ Defense cells that look out for invading micro-organisms ▪ Have the ability to engulf part of the antigen and present it to the macrophage cell

1. The skin’s first line of defense is the acid mantle in addition to the NMF. Bacteria (pH 7.47.6) are therefore alkaline so are deflected due to acidity of sebum and perspiration. Impaired or damaged barrier will lead to invasion of antigen. 2. If an invading organism enters the skin, the process begins with the Langerhan Cells found in the Stratum Spinosum. These are defense cells that look out for invading microorganisms and have the ability to engulf part of the antigen and present it to the macrophage cell for inspection (remember to mention that UVB destroys or inactivates Langerhans). 3. The Macrophage is a Phagocytic Cell (white blood cell guard) that will engulf and destroy the antigen. If it cannot cope with the antigen, the immune system becomes involved and the lymphocytes will be stimulated. 4. Lymphocytes consist of 2 main types; 1) T-cells and 2) B-cells. They are stimulated in the lymphatic circulation. T-cells are made up of messengers, killers and suppressors. Their function is to destroy the antigen.

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Skin Histology

LANGERHANS CELLS ▪ Found in the Stratum Spinosum ▪ Defense cells that look out for invading micro-organisms ▪ Have the ability to engulf part of the antigen and present it to the macrophage cell

1. The skin’s first line of defense is the acid mantle in addition to the NMF. Bacteria (pH 7.47.6) are therefore alkaline so are deflected due to acidity of sebum and perspiration. Impaired or damaged barrier will lead to invasion of antigen. 2. If an invading organism enters the skin, the process begins with the Langerhan Cells found in the Stratum Spinosum. These are defense cells that look out for invading microorganisms and have the ability to engulf part of the antigen and present it to the macrophage cell for inspection (remember to mention that UVB destroys or inactivates Langerhans). 3. The Macrophage is a Phagocytic Cell (white blood cell guard) that will engulf and destroy the antigen. If it cannot cope with the antigen, the immune system becomes involved and the lymphocytes will be stimulated. 4. Lymphocytes consist of 2 main types; 1) T-cells and 2) B-cells. They are stimulated in the lymphatic circulation. T-cells are made up of messengers, killers and suppressors. Their function is to destroy the antigen.

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Skin Histology

Dermis

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Skin Histology

DERMIS ▪ The dermis consists mostly of connective tissue and is much thicker than the epidermis ▪ Made up of 80% water, elastin fibers and collagen floating in a glycoprotein gel, the dermis is the connective tissue supporting the skin. ▪ Composed mainly of Collagen and 5% Elastin ▪ Provides structural support to epidermis ▪ Provides nutrition and waste removal for epidermis ▪ Responsible for the skin’s pliability and mechanical resistance and is also involved in the regulation of the body temperature. ▪ It contains sense organs for, as well as blood vessels, nerve fibers, sebaceous and sweat glands and hair follicles. What are the 2 Layers of the Dermis? 1. Papillary ▪ Blood vessels, nerve endings and receptors 2. Reticular (Immediate, Upper, Mid, Lower) ▪ Densely packed collagen and elastic fibers The basal cells in the stratum basale of the epidermis connect to the basement membrane by the anchoring filaments of hemidesmosomes; the cells of the papillary dermis are attached to the basement membrane by achoring collagen fibers. This organization creates the DERMALEPIDERMAL JUNCTION and according to Dr. Obagi, this is the region in which wrinkles begin to form. The papillary dermis is the more superficial of the two dermal layers. This is the most active dermal layer, and is constantly repairing damaged collagen and elastin tissue (vitality) as well as producing new collagen, elastin (contributing to aging and tightness) and glycosaminoglycans, which contributes to hydration. Below the papillary dermis is the thicker major layer reticular dermis. This layer is densely packed with collagen and elastic fibers. Cells within this layer include mast cells, fibroblasts, macrophages, and dermal dendritic cells. The papillary dermis is further dived into several layers: the immediate reticular dermis, the layer in which collagen fibers become thicker and more horizontal, and elastic fibers become less distinct; the upper reticular dermis, mid dermis and the lower reticular dermis.

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Skin Histology

DERMAL TISSUE TYPES The dermis is comprise of two tissue types: ▪ loose connective tissue and dense irregular connective tissue. ▪ Loose connective tissue derives its name based on the “loose” weave or arrangement of its fiber distribution. ▪ The papillary dermis is formed of loose connective tissue. ▪ Notice the distribution of elastin and collagen fibers, an now notice how that distribution changes as we move to the reticular dermis, which is derived from dense irregular connective tissue. ▪ This tissue type results from the “dense” concentration of collagen, elastin and reticular fibers

Loose Connective Tissue

Dense Irregular Connective Tissue

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Skin Histology

FIBROBLAST

▪ Master Cells” of the dermis ▪ Spindle shaped cells that lie among collagen fibers ▪ Produce collagen, elastic fibers and ground substance ▪ Can remove substances by secreting enzymes such as collagenase and elastase ▪ With age, they become smaller and less active

Most are located in the dermal papillae close to the epidermis, and found only in very low numbers in the deep layers of the dermis known as the reticular fibroblasts are the Master cells of the dermis. They are responsible for synthesizing our connective tissue elements including the collagen, elastic fibers, extra cellular matrix, and proteoglycan-glycosaminoglycans. They are more numerous and larger in the papillary dermis than in the reticular dermis. Fibroblasts control the turnover of connective tissue by secreting enzymes that degrade collagens (collagenases), elastin (elastinases), and proteoglycan and glycosominoglycans. As we age, fibroblasts become smaller and less active and thus fewer collagen and elastin fibers as well as glycosaminoglycans are produced.

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Skin Histology

DERMAL FIBROBLAST PRODUCE Dermal Fibroblast produce ▪ Collagen Type I ▪ Collagen Type III ▪ Collagen Type VII ▪ Elastin ▪ Hyaluronic Acid (Hyaluronin) ▪ Matrix Metelloproteinases (MMPs) FIBROBLAST SIGNAL Fibroblast cells have specially shaped receptors on their outside membranes that act as binding sites to which signal molecules with a matching shape. When the receptors are bound by the correct combination of signal molecules (called fibroblast growth factors, or FGFs), the fibroblast begins production of the appropriate protein.

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Skin Histology

COLLAGEN LEADS TO TENSILE STRENGTH ▪ Fibroblasts initially produce short collagen subunits called procollagen ▪ Collagen is composed of two identical polypeptide chains and a third that differs slightly in chemical composition that twist to form a helical structure ▪ dermis is composed primary of Type I and Type III fibers Short collagen subunit called procollagen are transported out of the fibroblast cells and later join together to form the complete collagen molecule. The polypeptide chains combine to produce more than 20 different combinations, however, our dermis is composed primary of Type I and Type III fibers. the structural difference between Type I and Type III collagen fibers. The structural difference is directly related to functional difference. Type I collagen provides resistance to tension, while Type III collagen contributes to the structural framework of our skin. Adult skin contains roughly 60-80% of Type I fibers and 15-20% of Type III fibers, which are primarily located in the papillary dermis.

Type I

Type III

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Skin Histology

COLLAGEN ORGANIZATION â–Ş Collagen makes up approximately 70% of the dry weight of the dermis, has great tensile strength. â–Ş The tensile strength of collagen allows the skin to serve as a protective organ against external trauma, much like the rebar in the Golden Gate Bridge protects us from the water below as we drive from one side to the other. In young skin that has not been exposed to the sun, mature collagen is cross-linked into collagen fibrils that come together in small groups of fibers, which are then organized into wavy bundles. They arrange themselves at 90 degree angles to form a mat-like pattern. The bundle formations are loosely arranged in the papillary dermis and become thicker in the deep dermis creating a great foundation and structure.

Loose Connective Tissue

Dense Irregular Connective Tissue

Rebar embedded in concrete

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Skin Histology

ELASTIN FIBERS ▪ Found in extracellular matrix in dermis ▪ Make up 2-4% volume of dermis ▪ Papillary area they are thin ▪ Reticular area they are thicker & greater in number ▪ Responsible for the wrinkling and sagging of aging skin Composed of the protein fibrillin and elastin made of simple amino acids, such as glycine, valine, alanine and proline. Elastic fibers are protein complexes that make up 2-4% of the dermal volume. It helps to keep skin flexible but tight, providing a bounce-back reaction if skin is pulled. Enough elastin in the skin means that the skin will return to its normal shape after a pull. It also helps keep skin smooth as it stretches to accommodate normal activities like flexing a muscle, smiling or opening and closing the mouth to talk or eat.

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Skin Histology

EXTRACELLULAR MATRIX (ECM) Collagen and elastin fibers are embedded in the ground substance of the extracellular matrix of the dermis.

Main function Maintain and support the Collagen and Elastin and turgidity/swelling in the cellular spaces. Keeping those protein fibers in balance and proportion. Also promotes the ability of the collagen and elastin fibers to retain moisture, therefore remain soluble. Facilitate cell adhesion, motility and cell-matrix interactions ▪ Soluble proteoglycans-Glycosaminoglycans ▪

Attract water molecules via osmosis, keeping the ECM and resident cells hydrated.

Help to trap and store growth factors within the ECM

▪ Hyaluronic acid ▪

Attracts 1000 times its weight in water

▪ Fibronectin ▪

Glycoprotein that binds ECM components (binds collagen fibers)

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Skin Histology

MAST CELL ▪ Cells of our immune system ▪ Scattered throughout the connective tissues of the body ▪ Mediate inflammatory responses such as hypersensitivity and allergic reactions ▪ Store a number of different chemical mediators—including histamine Mast cells are tissue cells of our immune system. Mast cells mediate inflammatory responses such as hypersensitivity and allergic reactions. They are scattered throughout the connective tissues of the body, especially beneath the surface of the skin, near blood vessels and lymphatic vessels, within nerves, throughout the respiratory system, and in the digestive and urinary tracts. Mast cells store a number of different chemical mediators—including histamine, interleukins, proteoglycans (e.g., heparin), and various enzymes—in coarse granules found throughout the cytoplasm of the cell. Upon stimulation by an allergen, the mast cells release the contents of their granules (a process called degranulation) into the surrounding tissues. The chemical mediators produce local responses characteristic of an allergic reaction, such as increased permeability of blood vessels (i.e., inflammation and swelling) Immunoglobulin E (IgE) antibodies and mast cells have been so convincingly linked to acute allergic reactions that it can be difficult to think of them in other contexts.

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Skin Histology

SEBACEOUS GLAND ▪ Located in the dermis ▪ Developed from the epithelial cells of the hair focllicle ▪ Activity is stimulated by androgens ▪ Inflammatory substance that induces a significant immune response: this resultant inflammation is manifested as acne, rosacea, seborrheic dermatitis, PIH, and scarring. The sebaceous glands are located in the dermis, the middle layer of the skin, and they develop from the epithelial cells of the hair follicle itself (the external root sheath of the hair follicle). Sebaceous gland ducts thus usually open up into the upper part of a hair follicle, called the infundibulum. Sebum is rich in waxes and esters that provide a favorable environment for bacteria Excess sebum, on the other hand, is detrimental. Hypersecretion of sebum leads to clogged pores, comedone formation, seborrheic dermatitis. Sebum is a highly inflammatory substance that induces a significant immune response: this resultant inflammation is manifested as acne, rosacea, seborrheic dermatitis, PIH, and scarring.

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Skin Histology

HYPODERMIS ▪ consists of lobules of fatty tissue made up of adipocytes ▪ functions as a buffer against blunt trauma ▪ Adipose cells provide us with fatty tissue for contouring and structural support

The subcutaneous tissue (from Latin subcutaneous, meaning 'beneath the skin'), also called the hypodermis, hypoderm (from Greek, meaning 'beneath the skin'), The types of cells found in the hypodermis are fibroblasts, adipose cells, and macrophages. The subcutaneous layer consists of lobules of fatty tissue made up of adipocytes FAT CELL.

Hypodermis

Dermis

Epidermis

This layer functions as a buffer against blunt trauma and gives the skin it appealing full and plump appearance. It also provides gliding ability to both the dermis and epidermis, which helps to make the skin more flexible. And unless you are a boxer receiving punches to the face there is nothing to stimulate this layer.

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Skin Histology

For profound beneficial restoration and maintenance of skin health the skin must be treated on the cell ular level with agents that target the different layers and cell of the skin that we just discussed. DR. Zein Obagi clinical experience have revealed that the areas of most concern in skin health include the following : the integrity of skin barrier function, duration of KMC, and presence of chronic inflammation. Skin health can be restored and maintained by directly targeting the different layers and cells of the skin.

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ZO

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MAINTAINING PROPER SKIN FUNCTION

This document is strictly private, confidential and personal to its recipients and should not be copied, distributed or reproduced in whole or in part, nor passed to any third party.

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Essential Topical Agents

Skin Barrier restore and maintain

Melanocyte Stabilization of melanocytes

AGENTS

AGENTS

▪ Retinol or retinoic acid

▪ High potency retinol (oleosome delivery)

▪ Alpha-hydroxy acids

▪ Ascorbic acid-2 glucoside

▪ Ectoin, glycerin, sodium hyaluronate

▪ Vitamins A, C and E

▪ Safflower oil/palm oil aminopropanediol esters,

▪ Hydroquinone

simmondsia chinesis (jojoba) esters

▪ n-Acetyl glucosamine

(ceramides to strengthen skin barrier)

▪ Tetrahexyldecyl ascorbate

BENEFITS

BENEFITS

▪ Promotes cellular renewal

▪ Breaks up existing pigmentation and rapidly

▪ Restores hydration ▪ Replenishes lipids to optimize skin barrier function

brightens skin tone ▪ Helps inhibit new melanin ▪ Serves as a non-hydroquinone alternative ▪ Provides antioxidant protection ▪ Corrects existing pigment ▪ Suppresses future pigment

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Essential Topical Agents

Collagen + Elastin Stimulation –wake up cellular

Mast Cell Elimination of chronic skin

AGENTS

AGENTS

▪ Disodium acetyl glucosamine phosphate and

▪ Lactose, milk protein

fermented red ginseng extra (lactobacillus +

▪ Palmitoyl glycine

red ginseng)

▪ Hydrolyzed algin

▪ ZPRO® ▪ Retinol in a micro-emulsion delivery or Tretinoin ▪ Palmitoyl tripeptide-1, palmitoyl tetrapeptide-7

▪ Marrubium vulgare (horehound) meristem cell culture (ZO-RRS2™) ▪ Leontopodium alpinum (edelweiss) meristem cell culture (ZO-RRS2™)

BENEFITS

BENEFITS

▪ Boosts collagen and hyaluronic acid

▪ Promotes healthy microcirculation

production ▪ Neutralize free radical oxygen species ▪ Helps improve the signs of aging, lines, wrinkles, dull skin

▪ Minimizes inflammation, diminishes skin redness ▪ Promotes healthy microcirculation ▪ Inflammatory modulation

▪ Replenishes lipids to optimize skin barrier function ▪ Stimulates cell renewal, improves penetration of active ingredients

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Essential Topical Agents

Sebaceous Gland Normalized surface oil, neutralize bacteria

AGENTS ▪ Micronized benzoyl peroxide (10%) ▪ Melaleuca alternifolia (tea tree) leaf oil

▪ Salicylic acid ▪ Sulfur ▪ Glycerin ▪ Kaolin, bentonite

BENEFITS ▪ Normalizes surface oil, neutralizes bacteria

▪ Absorb surface oils ▪ Inhibits inflammation ▪ Keep pore clean

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ZO® Principles of Skin Health Restoration

PRINCIPLES

DESCRIPTION

Skin Barrier

Corrects weakness and dryness in the epidermis by restoring water, lipid and protein balance, preventing trans-epidermal water loss and regulating natural skin exfoliation

Stabilization

Prevents acquired sensitivity to treatment while increasing the skin’s resistance to negative external and/or internal factors by protecting and maintaining normal cellular functions

Stimulation Wake up cellular activity

Stimulation is the process of improving both the epidermis and the dermis through the use of vitamin A (retinol/retinoic acid). Activates and upregulates dermal and epidermal cellular activity, optimizing fibroblast activity to increase the production of new and the repair of damaged collagen (firmness), elastin (tightness) and glycosaminoglycans (hydration). Reverses uneven texture. Upregulates angioblast function, which improves circulation with associated increased oxygen and nutrient delivery. Restores normal and even color tone with blending action.

Sebum Control

Prevents induction and progression of pigment conditions and chronic inflammation resulting from excess sebum output

Chronic Inflammation Elimination

Reduces cellular dysfunction, alteration of skin texture, true sensitivity, dyschromia, poor response to treatment, poor healing and accelerated aging while preventing resistance to treatment

Overcome Skin Resistance

Overcome Skin Resistance to medical topical agents by limiting their use. Skin can acquire tolerance and resistance to many topical agents, leading to treatment failure and complications

Hydration + Calming

Functional hydrators as alternatives to traditional moisturizers to reduce severity of reactions and irritation, increase tolerance and accelerate hydration from within without weakening treatment benefits

Smart Sun Protection

Using ZO®’s Triple Spectrum Protection, provides maximal sun protection to defend against UVA/UVB, HEV and IR-A exposure while synergistic antioxidants negate free radical stress

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ZO

®

SUPPORTING WORKBOOKS AT-A GLANCE PRODUCT GUIDE SKIN HEALTH RESTORATION PROGRAMS (Protocols)

This document is strictly private, confidential and personal to its recipients and should not be copied, distributed or reproduced in whole or in part, nor passed to any third party.

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