Barrier function & biomechanical properties of the skin
-
Upload
ahmed-amer -
Category
Documents
-
view
271 -
download
6
Transcript of Barrier function & biomechanical properties of the skin
Barrier Function & Biomechanical Properties of
the Skin
Maha Adel Shaheen, MDProfessor of Dermatology & Venereology
Ain Shams University
Skin Structure
1- Epidermis - Stratum Corneum
- Viable Epidermis
← BMZ →
2- Dermis
3- Hypodermis (Subcutaneous fat)
Viable Epidermis
• Basal Layer
stratum germinativum
• Spinous Layer intercellular bridges (desmosomes)
• Granular Layer
(KHG – Odland bodies)
Stratum Corneum
• 15-20 layers of terminally differentiated keratinocytes.
• Dead non-nucleated thin flat cells (squames) (corneocytes).
• Held together by lipids and desmosomes.
• Function: Epidermal Barrier
Epidermal Barrier(Brick and Mortar Wall)
• Site: lower stratum corneum.
• Function: protection from water loss & noxious physical, mechanical & chemical insults.
• Structure:1- Corneocytes (hard
building blocks).2- Intercorneocyte lipids
(space filling mortar).
Corneocytes1- KIF cytoskeletonTightly bundled keratin intermediate filaments aligned ≈ to the skin
surface.
2- Cornified cell envelope (CE)
• Uniform band located beneath the KC
plasma membrane.
• Formed of cross linked specific structural proteins.
Keratin Intermediate Filaments
- Rope-like fibers extending
from nucleus periphery.
- Mechanical support.
- Tissue specific expression
of heterodimers
(K5/K14 - K1/K10)
Structure of Intermediate Filaments
• Two dimers of cytokeratin group into a keratin tetramer by anti-parallel binding.
• This cytokeratin tetramer is considered to be the main building block of the cytokeratin chain.
• By head-to-tail linking of the cytokeratin tetramers, the protofilaments are originated, which in turn intertwine in pairs to form protofibrils.
• Four protofibrils give place to one cytokeratin filament.
CE Proteins• Involucrin • Loricrin• Keratolinin• pro (Filaggrin)• Desmosomal proteins: - desmoplakin - envoplakin - .............
• Keratinization specific multilamellar lipid sheets in-between corneocytes
• Formed in the granular cell layer Odland (lamellar) bodies
- Ceramides- Cholesterol & esters- Free fatty acids- phospholipids
Defects of Skin Barrier(Broken Bricks - Weak Mortar)
1- Atopic Dermatitis
2- Psoriasis
3- Lamellar Ichthyosis
4- Netherton Syndrome
5- Contact Dermatitis
Basement Membrane Zone( BMZ )
• Histopathological BMZ (PAS +ve)
• Ultrastructural BMZ
• Molecular BMZ
Human skin basement membrane as a target of autoimmune diseases
Diseases chch by autoantibodies directed against hemidesmosome
1- Bullous pemphigoid
2- Linear IgA bullous dermatosis
Diseases chch by autoantibodies directed against lower lamina lucida
1- Cicatricial pemphigoid with autoantibodies to bullous pemphigoid antigen
2- Anti-laminin cicatricial pemphigoid
3- Anti-p105 pemphigoid
Diseases chch by autoantibodies directed against sub-lamina densa
1- Epidermolysis bullosa acquisita
2- Bullous SLE
Molecular Basis of Inherited Skin Diseases
• Epidermolysis bullosa (EB)
EB Simplex ----- K5 & K14
EB Junctional ----- Laminin
EB Dystrophic ----- Collagen VII• Ichthyoses
Ichthyosis Vulgaris ---- Profilaggrin
XLRI ------- Steroid sulfatase
BIE ------ K1 & K10• Palmoplantar Keratodermas• Ectodermal Dysplasias
Extracellular Matrix
• Any material produced by cells & secreted into the surrounding medium.
• ECM is produced by cells & influences the behavior of cells.
3 major components
1- Fibrous elements (collagen, elastin, reticulin)
2- Link proteins (fibronectin, laminins,…)
3- Space-filling molecules ( GAGs)
Extracellular Matrix
Fibrillar Matrix (structural proteins)
• Collagen - Elastin - Reticulin
Extrafibrillar Matrix
• Glycosaminoglycans (GAGs)
• Proteoglycans
• Hyaluronic acid
Glycoproteins (adhesive function)
• Laminins, fibronectin, vitronectin .…..
ECM FunctionA- Structural Function:
• Skin elasticity, resilience, tautness.
• Strong adherence between epidermis and dermis by BMZ anchoring complexes -------> resistance against external sheering forces.
B- Regulation of cellular functions:
• Cell adhesion, migration, division, signaling, apoptosis …..
Collagen Molecule
• A triple helix of three extended protein chains wrapped around one another.
• Numerous rod like collagen molecules cross-link together to form un - extendable collagen fibrils.
• Collagen fibrils are striped because of the regular repeating arrangement of the collagen molecules within the fibril.
Collagens(26 types – 44 genes)
Skin Collagens• Collagen I, II, III
• Collagen IV (BM collagen)
• Collagen VII (Anchoring fibrils)
Elastin molecule uncoils when the fiber is stretched and spontaneously recoils when the stretching force is relaxed
Extrafibrillar Matrix
• Glycosaminoglycans (GAGs)
Large polysaccharide chains made up of repeating disaccharide units that are negatively charged and hold a large amount of water compared to other ECM molecules
• Proteoglycans
Protein and polysaccharide complexes
Mechanical Skin Properties
Tension: taut - tense - stretched firmly - not slack - resists deforming forces.
Elasticity: recoils or springs back to its original length or shape after being stretched or squeezed.
Resilience: springy- adaptive - readily recovering from shock.
Tensile Strength: the degree to which it can be elongated before it tears.
Mechanical Skin Properties
Cytoskeleton Supports the cell and gives it its shape
Glycosaminoglycans( GAGs) & Proteoglycans Viscoelastic properties & resistance to compression
Collagen fibers Tensile strength (resistance to breaking or tearing)
Elastic fibers Tension, resilience, elasticity
EDS Joint Hypermobility1. More than 10º hyperextension of
the elbows.
2. Passively touch the forearm with the thumb, while flexing the wrist.
3. Passive extension of the fingers or a 90º or more extension of the fifth finger (Gorling’s sign). This is used as a “Screen Test”.
4. Knees hyperextension greater than or equal to 10º.
5. Touching the floor with the palms of the hands when reaching down without bending the knees. This is possible as a result of the hypermobility of the hips, and not of the spine as it is commonly believed.
Cutaneous Mucinoses
A heterogeneous group of conditions caused by dermal fibroblasts producing abnormally large amounts of glycosaminoglycans → focal or diffuse dermal deposition.
H&E: bluish, feathery material H&E: bluish, feathery material between collagen bundlesbetween collagen bundles
Mucin Stains
• Colloidal Iron
• Alcian Blue
• Toluidine Blue
• Incubation of tissue in hyaluronidase eliminates the staining, confirming the presence of mucin
Lichen myxedematosus - Papular mucinosis - Scleromyxedema
The etiology is unknown. The disease is commonly associated with plasma cell dyscrasia.
The basic defect ≈ a fibroblast disorder → increased mucin deposition in the skin.
Most patients have a monoclonal paraprotein band, usually IgG type.
The association between this paraprotein and the mucin deposition is not clear, and the protein does not directly stimulate fibroblast proliferation.
Why Shar Pei Dogs Have So Many Wrinkles
• The genetic alteration in this breed multiplies the activity of an enzyme responsible for an excessive production of hyaluronic acid which gathers under the skin and produces wrinkles.
• Understanding this molecular mechanism will be used to learn more about human disorders such as mucinosis and to gain more knowledge on the ageing process.
Mucopolysaccharidoses• A group of metabolic disorders caused by the absence or
malfunctioning of lysosomal enzymes needed to break down glycosaminoglycans.
• Patients either do not produce enough of one of the 11 enzymes required to break down these sugar chains into simpler molecules, or they produce enzymes that do not work properly.
• Over time, these GAGs collect in the cells, blood and connective tissues.
• The result is permanent, progressive cellular damage which affects appearance, physical abilities, organ and system functioning, and, in most cases, mental development.
Lipoid Proteinosis
• Skin scarring, beaded eyelid papules, laryngeal infiltration → hoarseness, Infiltrates in the tongue and its frenulum limit lingual movements and cause speech difficulties.
• PAS positive hyaline material in the skin, upper aerodigestive tract & internal organs.
• Mutations in the extracellular matrix protein 1 gene (q21) .
• ECM1 = glycoprotein that binds to perlecan, the major heparan sulphate proteoglycan of the BM, as well as to fibrillar proteins (“biological glue” in the dermis, helping to regulate basement membrane and interstitial collagen fibril macro-assembly ).