Skin barrier function,skin conductivity

Michal Jurajda

Terminology

• Keratos = horn in Greek

• Cornu = horn in Latin

Skin is the body organ

epidermis

dermis

tela subcutanea

skin adnexa+

Skin functions

• Barrier functions (phys., chem. and biol.)

• metabolic functions (vit.D activation, excretion)

• immune function, APC (Langerhansovy buňky)

• Senzoring of temperatute and pain

• Thermoregulation

Skin barrier - epidermis

• Epidermal layers

Stratum corneum

Stratum basale

Stratum spinosum

Stratum granulosum

Stratum lucidum

Stratum dysjunktumStratum compactum

Skin barrier

• System of two compartments– „ bricks and mortar “

• keratinocytes (corneocytes)

• intersticium

Skin barrier

• „Bricks“– Keratinized cells

• „Mortar“– Produced by keratinocytes (Odland bodies,

lamellar bodies)– Excretions of skin glands

• FFA, ceramids, cholesterol

Skin barrier – cellular component

– Mechanic function– Hydratation– UV protection– Inflammatory response (APC)

Keratin

• Epithelial cells almost always coexpress pairs of type I and type II keratins, and the pairs that are coexpressed are highly characteristic of a given epithelial tissue.

• In human epidermis, 3 different pairs of keratins are expressed: keratins 5 (type II) and 14 (type I), characteristic of basal or proliferative cells; keratins 1 (type II) and 10 (type I), characteristic of suprabasal terminally differentiating cells; and keratins 6 (type II) and 16 (type I) and keratin 17 (type I), characteristic of cells induced to hyperproliferate by disease or injury, and epithelial cells grown in cell culture.

Filaggrin

• Protein from corneocytes

• In the deeper layers of epidermis connected to keratin

• In the upper layers of epidermis is hydrolyzed. Free aminoacids are released.

• Acidic pH and osmotic activity

UCA urocanic acid

• Originates from filaggrin.

• Acidic pH of the epidemmis

• Natural sunscreen

• Cis-UCA immunosupression

1.Ultraviolet C (UVC, 100-290 nm) are the shortest and most energetic portion of the UV spectrum. These highly energetic wavelengths are the most dangerous in terms of the damage it can inflict on living material. The important wavelengths in the UVC are removed within the atmosphere, mainly by absorption in the ozone layer and not reach the earth's surface in any quantity.

2.Ultraviolet B (UVB, 290-320nm) is the most damaging part of UVR that we encounter. It is currently thought to generate most of the photodamage to skin, though not all. UVB are wavelengths mostly blocked by dense clouds, closely woven clothing and glass window panes. Significant amounts are transmitted from blue sky in the middle of the day in summer. It is less dangerous when the sun is low in the sky, at high latitude in winter, and in early mornings and late evenings in summer.

3.Ultraviolet A (UVA, 320-400nm) is about 1000 times less damaging to the skin than UVB as measured by sunburn (Erythema) or damage to cell DNA. On the other hand, 20 times more UVA than UVB reaches the earth in the middle of a summer's day. It is not greatly affected by absorption and scattering in the atmosphere when the sun is low in the sky, and is now known to contribute significantly to the total exposure at moderate levels throughout the whole day and year. UVA penetrates deeper into the skin and leads to deeper damage than UVB does. It penetrates cloud cover, light clothing and untinted glass relatively easily, and may induce a degree of continuing skin damage over long periods, even when UVR exposure is not obvious.

Skin damage by UV rays

• direct- pyrimidin dimers formation – mostly thymin (UVB)- photoageing – induction/inhibition of gene expression

(↓colagen, ↑MMPs, ↑elastase)

• indirect- ROS formation (following excitation of „chromophores“ –

molecules containing conjugated double bonds and/or aromatic circles)

- retinoid depletion in skin- imunosupression (esp. UVA)- folate degradation – systemic effects

Melanin – protection against ultraviolet radiation

Interstitial compartment

– Permeability– Deskvamation– Antimicrobial effect– Absorption of drugs or poisons– Hydratation

Lamellar bodies (LB)

• Lipids + enzymes producing FFA cholesterol a ceramids - permeability

• Structural proteins (corneodesmin), serine proteases, proteases inhibitors – regulation of skin desquamation

• Antimicrobial peptides (β defensins, cathelicidiny – evolutionary old proteins)

Cosmetics and the skin barrier

• Cosmetics x pharmaceuticals

• Different sale regulations

• Different declaration of ingredients– Cosmetics: according to % in content– Pharmaceuticals: according to active

component

INCI

• International Nomenclature Cosmetics Ingredients – unified nomenclature for cosmetics

• Cosmetics, Toiletries & Fragrance Association (CTFA) – author of INCI

FD&C Yellow#5 Color

FD&C Red#40 Color

Ammonium Polyacrylate Dispersant

Isohexadecane Emollient

C13-14 Isoparaffin Emollient

Isopropyl Isostearate Emollient and skin conditioner

Sucrose Polycottonseedate Emollient and skin conditioner

Sorbitan starate Emulsifier

Laureth-7 Emulsifier

Sucrose Cocate Emulsifier

PEG 100 Stearate Emulsifier

Stearic Acid Emulsifier

Fragrance Fragrance

Examples

Diesodium EDTA Chelating agent

Titanium Dioxide Opacifying agent

Sodium Hydroxide pH adjuster

Benzyl Alcohol Preservative

Ethyl Paraben Preservative

Propyl Paraben Preservative

Methyl Paraben Preservative

Panthenol Pro Vitamin B5/Skin Conditioner

Dimethicone Skin Conditioner

Dimethiconol Skin Conditioner

Glycerin Skin conditioning agent/humectant

Water Solvent

Polyacrylamide Thickener

Cetyl Alcohol Thickener and skin conditioner

Stearyl Alcohol Thickener and skin conditioner

Niacinamide Vitamin B3, skin conditioner

Tocopherol Acetate Vitamin E, emollient and Skin Conditioner

Skin cleanser cosmetics

Water Solvent

Sodium laureth sulfate Mild cleansing and lathering

Sodium lauroamphoacetate Mild cleansing and lathering

PEG-6 caprylic/capric glycerides Moisturizer/emollient

Palm kernel acid Thickener/skin conditioner

Magnesium sulfate Thickener

Glycerin Moisturizer/humectant

Cocamide MEA Mild cleansing and lathering

Citric acid Adjusts pH

Maleated soybean oil Moisturizer/emollient/occlusive

Fragrance Fragrance

Polyquaternium-10 Skin conditioner and emollient

Disodium EDTA Chelator

Sodium benzoate Preservative

DMDM hydantoin Preservative

The importance of skin barrier function – why we are interested

in?

• Protection against environment– Professional exposure

• Skin diseases influence skin barrier– Atopic or contact dermatitis

• Drugs absorption

How to test skin barrier

• Resistence against given chemical compound

• Stripping tests

• Transparency test

• Transepidermal water loss

• Chemical analysis of skin eluates

Transparency test

Atopic dermatitis

• Sensibilization• Allergic reaction

Atopic dermatitis

Prick test

Contact dermatitis

• Haptens• nickel

Skin barrier tests

• Burckhardt test

• Locher test, nitrazolium yellow

• Skin conductivity

Measuring of skin conductivity by Dermotest

• AC 32Hz; 0-500 μS.

• standard load iontophoresis 1.5 mA, with NaCl (physiological saline).

The device measures 5 characteristic values (V1-V5):1min after the start (V1)30 a 60s after the start of electrophoresis (V2, V3)30 a 60s after switching off the electrophoresis(V4, V5)

Normal values

• V1 less than 30 μS

• V3 up to 200-300 μS

• V5 return to initial values

• Test might be repeated after 15 minutes with the same result

desquamation

occlusion

Course of atopic dermatitis therapy