epidermis 1 dr.ashwini n vims & rc
TRANSCRIPT
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EPIDERMIS -1MODERATOR DR.JAIDEV.
Dr. ASHWINI.N
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SKIN
• Skin is the largest organ of the body accounting for 16 - 20% of total body weight , with a surface area of 1.8 – 2 m2 .
• Two main kinds of skin - Glabrous Skin ( non-hairy skin).
- Non Glabrous Skin.(hairy skin).
• Skin is divided into 3 layers
a) Epidermis- outermost layer , serves as barrier between exterior & body’s interior environment and is responsible for cornification.
b) Dermis- a deeper layer ,provides structural support to skin.
c) Subcutis- containing fat and connective tissue.
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EPIDERMIS
• Is metabolically active, stratified squamous epithelium.
• Consisting of 4 type of cells.
1.Keratinocytes.
2.Melanocytes.
3.Langerhans cells.
4.Merkel cells.
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Layers Of Epidermis
• Stratum basale.
Stratum malpighian.
• Stratum spinosum.
• Stratum granulosum.
• Stratum lucidium.
• Stratum corneum.
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STRATUM BASALE
• Basal cell layer, consisting of 1-2 layers of columnar/cuboidal keratinocytes ,with large oval nuclei & basophilic cytoplasm.
• The cells in basal layer(keratinocytes) are interconnected by intercellular bridges Desmosomes.
• Basal keratinocytes are attached to subepidermal basement membrane by modified desmosome-Hemidesmosome.
• Basal keratinocytes are interspersed with melanin producing cells, melanocytes at regular interval.
• Stratum basale is the primary site for MITOTIC ACTIVITY
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STRATUM SPINOSUM
• 8-10 layers of cells.
• Keratinocytes in this layer are Polyhedral in shape, with round nucleus, basophilic cytoplasm.
• Spinous processes (abundant desmosomes) hence the name.
• The cells in upper spinous layer are larger & become more flattened and contain organelles “lamellar granules”
• The cells in spinous layer contain large and conspicuous bundle of keratin filaments Tonofibrils, that insert into desmosome peripherally.
• Limited cell division.
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STRATUM GRANULOSUM
• 2-5 Cell layer thick.
• Diamond shaped cells with intracellular basophilic keratohylinegranules, with deeply basophilic cytoplasm.
• Cytoplasm of the keratinocytes in this layer contain lamellatedgranules known as odland bodies.
• Discharge their lipid components into intercellular space, functions asbarrier & intercellular cohesion within the stratum corneum
• Keratohyline granules forms 2 structures.
a)Inter fibrillary matrix or filagrin- that cements keratin filaments
together
b) marginal bond- provides strength and flexibility.
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STRATUM LUCIDIUM
• Is a thin layer of translucent cells seen in thick epidermis of Palms & Soles.
• This layer is present between stratum granulosum and corneum.
• Cells in this layer are still nucleated and referred as “transitional cells”.
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STRATUM CORNEUM
• Outermost layer of epidermis.
• Composed of 20-25 layers of cornified cells.
• Made up of terminally differentiated, dead keratinocytes known as Corneocytes.
• These cells are flat, anuclear & devoid of cytoplasmic organells.
• Corneocytes contain soft keratin
• Cells are arranged together like “ bricks in a wall”
• Fluorescent staining shows cells arranged in orderly vertically stacks.
• The journey of cells from basal layer to surface is called Epidermal turnover or transit time – 52 to 75 days.
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EPIDERMOPOISES
• The epidermal thickness and the number and size of epidermal cells remain constant, with the rate of cell production matching the rate of cell loss.
• 3 populations of cells exist in the basal layer:
- Stem cells.
- Transient amplifying cells
- Post mitotic cells.
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• Keratinocyte stem cells give rise to all the layers of the epidermis, with the majority of these cells committed to terminal differentiation.
• Stem cells have a large capacity for proliferation.
• A transient amplifying cells can undergo a limited number (up to 5 to 6 times) of mitotic divisions.
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CELL CYCLE
• M or Mitotic phase of division
• G1 post mitotic phase or interphase
• S or phase of DNA synthesis
• G2 or Premitotic phase or short resting
• G-o phase or quiescent phase
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• The time taken by keratinocytes to pass from the basal layer to the stratum corneum and the skin surface is called the epidermal turnover time.
• It ranges from 52 to 75 days.
• The approximate transit time from the basal layer to stratum corneum is 12 to 19 days.
• through the stratum corneum is 14 days.
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Regulation of Epidermopoiesis
• A) Stimulatory signals:
1.Human epidermal growth factor (EGF) –
6 kDa polypeptide.
Stimulates cell proliferation and differentiation.
2 Transforming growth factor-α (TGF-α)-
A polypeptide synthesized by epidermal keratinocytes.
Stimulates growth of keratinocytes by an autocrine method .
after binding to human epidermal growth factor receptor (EGFr).
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• 3 Amphiregulin-
Autocrine keratinocyte growth factor regulated by cellular glycosaminoglycans and upregulated by EGF and TGF-α.
• 4. cytokines –
interleukin-1 & 6 can also stimulate the growth of keratinocytes.
others -PDGF, IL-1β and TNF .
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• B) Inhibitory signals:
Epidermal growth is inhibited by a negative feedback mechanism.
- Transforming growth factor-B, inhibits the growth of keratinocytes.
- IFN-α and -γ have cytostatic effects on keratinocytes.
- TNF-α is cytostatic on keratinocytes
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• C) Apoptosis: programmed cell death
A major cellular homeostatic mechanism in the skin.
Terminal differentiation of epidermal keratinocytes occurs by modified apoptotic programs.
• D) Signal transduction pathways:
Growth factors.
Cyclic 3,5-adenosine monophosphate (cAMP).
Protein kinase C, inositol phosphate and protein tyrosine kinase
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• E) Integrins:
play role in bidirectional communication that can result in a change in gene expression, pH and calcium fluxes.
• F) Others:
low calcium level inhibits differentiation of keratinocytes but
stimulates their proliferation.
Vitamin A and retinoic acids are required for normal morphogenesis
and differentiation
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TONOFILAMENTS
• Basal and lower portion of spinous zone of keratinocyte-
• contain abundant Rough Endoplasmic reticulum Ribosomes, Golgi apparatus ,mitochondria.
• Synthesize tonofilaments- 7.0nm in diameter .
• Also known as Keratin intermediate filaments
• Later becomes keratinous protein.
• They are oriented along major axis of cells.
• aggregate into bundles to form fibrous protein termed as Alpha keratin.
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FUNCTIONS OF TONOFILAMENTS
1. Flexibility and elasticity to cornified layer.
2. Cytoskeleton of keratinocytes,
3. Modulate shape of keratinocytes.
4. Promotes centralisation of nucleus.
5. Implement cell-cell adhesion via desmosomes.
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KERATINS
• Filamentous cytoskeleton of all mammalian cells including epidermal keratinocytes.
Contains-
• Actin containing microfilaments 7nm in diameter.
• Tubulin containing microtubules 20-25 nm in diameter.
• Intermediate filament 7-10nm in diameter.
• More than 30 keratins have been noted.
Distinct and separate genes and mol. Wt-40 to 67 KDa
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• Keratin genes -2 groups
Type I (basic)- 1 to 8
Type II (acidic)-9 to 19
• one basic and one acidic forms heterodimers which wrap around by hydrophobic interaction
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KERATOHYALINE GRANULES
• Source of protein (Profillagrin → Fillagrin).
• Electron-dense bodies devoid of internal structure but are biochemically complex.
• They appear first in upper part of spinous zone& become prominent in granular zone.
• Disappear as they enter cornified layer.
• Contains cysteine-rich proteins whose disulphide bonds contribute to chemical inertness & strength of cornifed layer
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FILLAGRIN
• Also known as Filament aggregating protein.
• Histidine rich, cat-ionic protein.
• Functions as an “Interfilamentous glue” to aggregate & align keratin filaments within cornified cells.
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LAMELLAR GRANULES
• Also known as odland bodies.
• Measures about 300 nm in diameter.
• Contain free sterols, polar lipids and hydrolytic enzymes.
• Appears at the top of spinous zone, near Golgi apparatus of keratinocytes & migrate into cytoplasm, fuses with plasma membrane.
• Contents are discharged into intercellular spaces.
• Once contents are discharged, they become organised into lamellae and provide structural basis for the barrier of epidermal permeability.
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CELLS OF EPIDERMIS
MELANOCYTES
Dendritic cells, synthesize & secrete melanin containing organelles-melanosomes.
• Derived from precursors in the neural crest.
• Found during 8th week of fetal life.
light microscope:
-Clear cells in the basal row of epidermis.
H & E
-Small basophilic nucleus & dendritic cytoplasm.
Dendrites of melanocytes may be revealed when melanin is stained blackwith silver salt
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Epidermal melanin unit
36 keratinocytes are associated with each melanocyte.
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• FUNCTIONS
1. Absorbs UV light and protect the skin from solar UV damage.
2.Melanin functions as a scavenger of free oxygen radicals and thus protects cells
3.Imparts various colours to hair.
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Langerhans cells
• Described by Paul Langerhan.
• Derived from mesenchymal precursors in bone marrow.
• Dendritic cells situated in middle of the epidermis.
• They constitute 2% to 8% of total epidermal cell population.
• Enter the epidermis at about 12 weeks
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• Conventional microscope:
clear cells, pale staining and have convoluted nuclei.
• Electron microscopy:
-They demonstrate a lobulated nucleus, clear cytoplasm, well defined
endoplasmic reticulum ,Golgi complexes and lysosomes.
-Langerhans cells have distinctive rod or racquet shaped
granules [BIRBECK Granules].
-They resemble Tennis racquet.
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• FUNCTIONS:
1. Plays role in immune process like ACD, allograft rejection, immune tolerance.
2. Defence against micro organisms.
3. Regulation of epidermal differentiation.
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MERKEL CELLS
• In 1875,FRIEDRICH MERKEL identified at base of rete ridges cells that were in contact with nerve fibrils and named them tastzellen or touch cells.
• They originate in the epidermis itself, presumably from germinative keratocytes.
• Appear in fetal skin by 16th week of gestation.
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• They have pale staining cytoplasm
• Nucleus is lobulated & the margins of cells project cytoplasmic spines towards keratinocytes.
• They have characteristic spherical granules which are membrane limited with a dense central core.
• These cells are embedded in basal layer & form desmosomal connections with the surrounding basal keratinocytes.
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FUNCTIONS
• Slowly adapting type I mechanoreceptor Low threshold touch receptors.
• most sensitive to vibrations at low frequencies, around 5 to 15 Hz.
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INTERCELLULAR JUNCTION
• Links adjacent keratinocytes.
• Responsible for mechanical ,biochemical , signalling interactions between cells.
Components include:
1.Desmosomes
2.Adherens junction.
3.Gap junction.
4.Tight junction.
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DESMOSOMES
-The major adhesion complex in epidermis.
- Anchors keratin intermediate filaments to the cell membrane.
- Bridges adjacent keratinocytes.
- Ultrastructure: cell membrane of two adjacent cells forms a symmetrical junction with a central intercellular space of 30 nm containing a dense line.
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• Components of desmosomes in epidermis:
a) Desmosome cadherin's.
b) armadillo family of nuclear & junctional proteins.
c) Plakins.
Cadherins -1. Desmoglins (Dsg 1-4)
2. Desmocollins (Dsc 1-3)
They are trans membranous calcium rich glycoprotein.
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• The intercellular parts of glycoproteins are attached to keratin filament network via desmoplakin, plakoglobin and other macro molecules.
• Desmosomal proteins acts as autoantigen in various immunobullous blistering disorders.
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ADHERENS JUNCTIONS
• Electron dense , transmembrane structures that engage with actin skeleton.
• They contribute to- epithelial assembly, adhesions, barrier formation, cell motility and changes in cell shapes.
• Characterised by: 2 opposing membranes separated approximately by 20 nm & 0.2 - 0.5 micro metre in diameter.
• Comprise of two basic adhesive units:
1) nectin – afadin complex.
2) cadherin complex.
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• mutations have subsequently been reported in the CDH3 gene, which encodes P-cadherin; these mutations result in autosomal recessive hypotrichosis with juvenile macular dystrophy.
• P-cadherin mutations are also found in a different disorder, ectodermal dysplasia–ectrodactyly–macular dystrophy (EEM) syndrome.
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GAP JUNCTION
• clusters of intercellular channels, known as connexons, that directly form connections between the cytoplasm of adjacent keratinocytes (and other cells).
• Connexons originate following assembly of six connexin subunits within the Golgi network that are then transported to the plasma membrane.
• The connexins are divided into three groups (α, β and γ).
• The formation and stability of gap junctions can be regulated by protein kinase C,calcium concentration, calmodulin, adenosine 3′,5′-cyclic monophosphate (cAMP) and local pH
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• FUNCTION : permits sharing of low-molecular-mass metabolites (<1000 Da) and ion exchange between neighbouring cells, thus allowing intercellular coordination and uniformity to maintain tissue/organ homeostasis in multicellular organisms.
.
• Gap junction communication is essential for cell
synchronization
differentiation.
growth and metabolic coordination of avascular organs, including
epidermis.
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TIGHT JUNCTION
• Tight junctions are the major regulators of permeability in simple epithelia, are also present in skin.
• They key role in skin barrier integrity and maintaining cell polarity.
• The principal structural proteins of tight junctions are the claudins, transmembranous proteins - junctional adhesion molecules (JAMs) and the occludin group of proteins.
• The main claudins in the epidermis are claudin 1 and 4.
• Transmembranous proteins do not bind to one another but the claudins and occludins can bind to the intracellular zonula occudens proteins ZO-1, ZO-2, ZO-3.
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• These proteins can also interact with actin thus providing a direct link with the cytoskeleton.
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THANK YOU
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