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The Epidermis

BASICS FUNCTION
• Self-replicating • Barrier:
• Mostly keratinocytes – Stratum corneum*
• Keratinization
• Assemblage of cornified • UV absorbing:
envelope
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Melanin
do not distribute.

• Melanocyte (8-10% – Tranurocanic acid

epidermal cells) • Antimicrobial
– Synthesize melanin
• Antioxidants
– UV protection
• Inflammatory
• Langerhans (2-3%) • Xenobiotic absorption
– Immuno-surveillance
 Corneocyte
core

BRICK
Protein
cell
envelope
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Lipid
envelope
MORTAR

Nemes and Steinhert

1999
• Lipid envelope (5nm): monolayer of ceramides. Interdigitate with other intercellular lipids to complete barrier.
Covalently linked by ester bonds to CE
• Initial scaffold (2-3nm): involucrin (75% mass) onto periplakin, envoplakin, desmoplain
• Reinforcement: loricrin, interconnecting SPR (small proline rich proteins (cornifins, pancornulins)
• Integration of CE: keratin cytoskeleton direct crosslinked to CE cytoplasmic surface
 What is most important for SC functionality

• pH
• Lipid
content/form
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ation
• H2O
 What happens when pH increases

↑ Inflammation

Consequences of ↓ Stratum corneum

elevated pH
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↓ Permeability barrier

Lynde CW et al. Clinical & Aesthetic dermatology. 2014;7(3):40-48

Higher pH = Higher Breakdown

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 • S corneum pH 4.5 -6.5
• Regulates many stratum corneum enzymes
– Ideal at pH 6.5 (S gran interface)
• Phospholipase A2 (makes free fatty acids)
Deeper S corneum

• Steroid sulfatase (breaks down cholesterol)

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– Ideal at pH 5.5 or lower
– B-glucocerebrosidase (makes ceramides)
– Sphingomyelinase (makes ceramides)
– Ideal at pH 7
• Proteases --> Desquamation of top layer
– Generate the active forms of the primary cytokines IL-1α and IL-1β
• Neonates higher stratum corneum pH à decr perm barrier
homeostasis, incr fragility

J Invest Dermatol. 2006;126:2074–2086.

 Intercellular Lipids

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The sea of FAT

 Role of SC lipids
• The SC lipids consist of an equimolar mixture of:
– ceramides (45–50% by weight)
– cholesterol (20–25%),
– free fatty acids (10–15%)

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 Disorder of Ceramides
Disease Defect Altering…
Aged skin Incr ceramidase Decr cer 1 (total and linoleate)
Xerosis Incr ceramidase Decr linoleate in cer 1
Farber dz Def acid ceramidase Incr in fibroblast ceramide
Atopic *Def spingomyelinase Decr cer 1 (total and linoleate), 3
*Induction of novel
glucosylceramide
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sphingomyelin deacylase
Ichthyoses ? Decr ceramide 1

Psoriasis Decr Sphingomyelinase Decr cer 1, 3,-5, 7. Incr cer 2 c creation of

cer 2’, 5’
Acne ? Decr linoleate in cer 1

Gaucher’s Decr glucocerebrosidase Decr ceramides

disease
Geilen 1997, Higuchi 2000, Coderch 2003
 Disorder of Ceramides
Disease Defect Altering…
Aged skin Incr ceramidase Decr cer 1 (total and linoleate)
Xerosis Incr ceramidase Decr linoleate in cer 1
Farber dz Def acid ceramidase Incr in fibroblast ceramide
Atopic *Def spingomyelinase Decr cer 1 (total and linoleate), 3
*Induction of novel
glucosylceramide
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sphingomyelin deacylase
Ichthyoses ? Decr ceramide 1

Psoriasis Decr Sphingomyelinase Decr cer 1, 3,-5, 7. Incr cer 2 c creation of

cer 2’, 5’
Acne ? Decr linoleate in cer 1

Gaucher’s Decr glucocerebrosidase Decr ceramides

disease
Geilen 1997, Higuchi 2000, Coderch 2003
 What about the Water?

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 Skin Hydration can be affected by any
one of these…

Desquamation Water in Dermis

(cell adhesion proteins) (GAGs)

Water retention Optimization of lipids

capacity (HA and glycerol)
Natural Moisturizing
pH are property of GW Dermatology.
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Transport of water in Thickness of Epidermal

and around the Compartment
(Keratinocyte proliferation)
epidermis
(aquaporins) Inflammation

Vascular permeability
Sensory aspect of dry skin (itching,
burning)

Filaggrin
Keratinocyte Differentiation
 Natural Moisturizing Factors
• Humectants
– Hydroscopic molecule absorbs
water
• Proteolysis filaggrin à AA
and derivatives
– Humectants:These slides are property of GW Dermatology. Please do not distribute.
• **Pyrrolidone carboxylic acid,
powerful humectant (from
glut)
• Lactates**, urea
• What’s the problem?
– NMF get washed out
– UV, humidity – interferes filaggrin
breakdown
– Age – less profilaggrin, less NMF

Journal of Cosmetic Dermatology, 6, 75–82

 From the Outside In: Immediate protection

• Classes of Moisturizing Ingredients:

– Emollients
– Humectants
– Occlusives
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– Skin Conditioning agents

 Clinical Context: What’s a moisturizer?

• Emollients
– Makes the skin feel
soft and smooth
– Maintain not repair
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– Not long term
 Clinical Context: What’s a moisturizer?

• Humectants
– Glycerol #1
– Enhance water
absorption from the
dermis intoThese
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epidermis
• Need occlusive agent
to prevent TEWL
– In humid conditions,
absorb water from
the external
environment
17 5/7/20
 Clinical Context: What’s a moisturizer?

• Occlusive
– Creams/ointments
– Hydrophobic barrier (Protectant), dec TEWL
– Limitations : odor, potential allergenicity, and
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the greasy feel

5/7/20 | 18
 Clinical Context: What’s a cleanser?

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http://dx.doi.org/10.12788/j.sder.0022
 Surfactants in Personal Cleansers
Ammonium/Sodium Lauryl Sulfate Cocamidopropyl Betaine

where M+ = NH4+ or Na+ fatty acyl group = C8 – C18 coconut acyl, C12 shown

Sodium Laureth Sulfate

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PEG-80 Sorbitan
Laurate

where n = 1 – 4 mol EO

Sodium Trideceth Sulfate

where x + y + z = 80 mol EO
where R = linear or branched C13 alkyl
and
n = 2 – 4 mol EO
EO = ethoxyl groups.
 Surfactants
• Amphiphilic O
S
O
Na hydrophilic
head
O
– Hydrophobic component O

scavenges oils, soil, and

other contaminants from
the skin
– HydrophilicThese
component
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allows their removal from
the skin by rinsing with
water. lipophilic
tail
• Surfactants form
Micelles
– Faster they form, the
less they penetrate
 Negative Consequences of Cleansing
With Surfactants

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www.themomsbuzz.com/moms_buzz/health/index.html

Walters RM, et al. Dermatol Res Pract. 2012;2012:495917.

Rieger MM. Cosmetics & Toiletries. 1995;110:31-50.
Ananthapadmanabhan KP, et al. Dermatol Ther. 2004;17:6-25.
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So what are we seeing now?

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 And this could happen…

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 Let’s….

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