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Skin Skin is the largest organ in the body. Surface area : 2 m2 , 10% total body mass Weight : 5 Kg Composed of : 1.A stratified cellular epidermis 2.Dermis of connective tissue 3.Subcutaneous fat ( Hypodermis) 4.Dermal-epidermal Junction 5.Skin Appendages
2 Types of Skin: 1. Glabrous ( Non Hairy ) 2. Hair Bearing Skin Glabrous : groved surface with alternating ridges (Dermatoglyphics) Compact Stratum corneum ( 10 times of flexures) Encapsulated sense organs with in dermis. Lack of hair follicles and sebaceous glands. Hair bearing skin: Lacks encapsulated sense organs .
Origin of SkinProspective epidermis Prospective mesoderm Neural Crest (Pigment Cells)
Origin of EpidermisFrom the Ectoderm Notch and Wnt signalling pathways
3rd week Single Layer epidermis 4-6th week 2 layer
Periderm Straitum germinativum
10th week Desmosomes and hemidesmosomal protein 8-11th weeks Middle layer and microvilli appears 12-16th weeks Intermediate layers and numerous microvilli 15th week Filaggrin protein in granular layer 21st week Keratohyaline granule increases in uppermost layer 24th week Periderm shed vernix caseosa
Hair follicles- 9 weeks Sweat glands-9 weeks:palms and soles 15 weeks:other area Sebaceous glands-15 weeks Nails-3rd month Langerhans cells-12 weeks Merkel cells-16 weeks Mast cells-6-14 weeks Melanoblast-6-14 weeks
TIME Schematic overview of embryonic development of human skin
EpidermisEpidermis is terminally differentiated, stratified squamous epithelium. Renews continuously and forms derivative structure. Thickness : 0.05-0.1mm Mainly composed of Keratinocytes : 95% of total cells other cells: Melanocytes, Langerhans cells and Merkel cells. Keratinocytes progressively moves outwards from their attachment to the epidermal basement membrane forming several layers. On morphological grounds: 4 layers 1.Stratum basale 2.Stratum Spinosum 3. Stratum Granulosum 4. Stratum Corneum
STRATUM BASALE: STRATUM GERMINATIVUM
Continuous layer,1 cell thick,(2-3 cell thick in glabrous skin) Cells are small cuboidal with large dark stained nuclei dense cytoplasm, contains many ribosome and dense tonofilamament bundle. In addition , membrane bound vacuoles containing pigmented melanosomes transferred from melanocytes by phagocytosis. Is Primary site for mitotically active cells. Stratum basale attached to BMZ via keratin intermediate filament K5\K14 to hemidesmosomes of BMZ. Applied aspect-k5/k15 mutation causes epidermolysis bullosa simplex
Stratum Spinosum: Prickle cell layerSpine like appearance of cell margin in the Histologic section. 8-10 cell layers thick. On Histological section : Cells are polyhedral with a rounded nucleus. As these cells differentiated and moves upward through epidermis, become proggressively flatter and develop organelles known as lamellar granule. Also contain large bundle of Keratin filaments organizes around the nucleus and intersected into desmosomes peripherally. Spines are abundant desmosomes.
STRATUM GRANULOSUM : 2-5 Cells Layer Thick. Granular layer due to the presence of intracellular Basophillic Keratohyaline granules which contains Profilaggrin, Keratin filament, Loricrin . KERATOHYALINE GRANULES: particles of irregular shape, and occurring randomly in rowes and lettices. This layer also contain smaller lamellar granular or Membranes coating granules / odlands bodies . They discharge their lipid content into the extracellular spaces . Cornified envelop begins to form here. APPLIED ASPECT:Upper spinous and granular layer keratinocytes involves in Icthyosis bullosa of Siemens.
STRATUM CORNEUM 20-25 layer thick,outer most layer. Has cornified cells (corneocytes) No nucleus and cytoplasmic organelles. Flattened keratin filament align into macrofibres due to fillagrin. Fillagrin is protein component in keratohylaine granules. Profillagrin : in F granules ,minor contribution. Membrane associated proteins : periplakin , envoplakin, epiplakin ,desmoplakin as well as plectin. Filaggrin provides interfilamentous material. Corneocyte has a insoluble CORNIFIED ENVELOPE with in Plasma membrane. Formed by involucrin and loricrin (soluble protien) Others precursors : small protein rich protein (SPR1) = cornifin and pancornifin, SKALP / elafin, keratolinin / cystatin.
STRATUM LUCIDUM In palmoplanter skin. Additional zone. Electone lucent. Present between statun granulosum and stratum corneum. Cells are still nucleated called as TRANSITIONAL CELLS
KERATINOCYTESEctoderm derived cells. Composes of Actin : 7 nm micro filament Tubulin : 20-25 nm microtubules Inter mediate filament : 7-10 nm Keratinocytes contain : keratin intermediate filament type I ( Acidic) type II ( Basic) In Simple epithelium : K8 /K 18 In stratified epithelium = K 5/K14 In Suprabasal layers : K 1/K10 for epidermal differentiation.APPLIED ASPECT: 1.SUPRABASAL KERATINOCYTES-BULLOUS CONGENITAL ICTHYOSIFORM ERYTHRODERMA. 2.BASAL KERATINOCTES-EPIDERMOLYSIS BULLOSA SIMPLEX.
Melanocytes are dendritic cells derived from Neural crest . Reside in Basal layer primarily. Pale staining cytoplasm, ovoid nucleus and pigment containing melanosomes. Melanocytes are in contact with Keratinocytes through their processes but do not form junction with them at any level. One melanocyte is in contact with 36 basal and suprabasal keratinocytes. This group known as EPIDERMAL MELANIN UNIT. 2 forms of melanin pigment: Brown / black eumelanin. Red /yellow phaeomelanin. APPLIED ASPECT: Reduced in Piebaldism and wardenberg syndrome. Defective pigment production or processing:Albinism and Chediak-Higashi syndrome.
MERKEL CELLS.0.2-5% of total cells Post mitotic cell ,slow adapting type I mechano receptors (Fine Touch), located amongst basal keratinocytes . found in hairy skin , tactile areas of glabrous skin, taste buds, anal canal, labial epithelium and eccrine sweat glands. Oval cell ,Have large bilobed nucleus and clear cytoplasm. Contain numerous neurosecretory granules. Forms close connection with sensory nerve endings known as MERKEL CELLS NEURITE COMPLEX. In glabrous skin: clustered near the unmyelinated sensory nerve endings and forms TOUCH SPOTS at the bottom of rete ridges known as Hair discs ,Touch domes, Touch corpuscles or Iggo discs. In hairy skin: also clustered in rete ridges and in the outer root sheath of hair follicle where the arrector pilli muscles attach. APPLIED ASPECT: absent in vitiligo lesions Merkel cell carcinoma.
LANGERHAN CELLS They constitute 2-3% of total cells. Dendritic cells similar to melanocytes but free from pigment and dopa negative and derived from bone marrow. In combination with macrophages and dermal dendrocytes represent the skins mononuclear phagocyte system. Can also release cytokines as IL-1 to promote lymphocyte chemotaxis and activation . Are intraepidermal macrophage. Pale stained cytoplasm with lobulated nucleus, well developed endoplasmic reticulum, golgi complex and lysosomes. Mostly found in a suprabasal portion but distributed throughout the basal spinous and granular layers. Possess a characteristic -BIRBECK GRANULES. Also found in outer root sheath of hair follicle, secretory duct of sebaceous gland and in the epithelium of the crypt of Human tonsils. APPLIED ASPECT: CHRONIC DERMATITIS CHRONIC LEISHMANIASIS HIV INFECTION
Epidermal attachment complexes.Desmosomes Adherens junction Gap Jnction Tight junction
DESMOSOMES:Are the major adhesion complex in epidermis, anchors keratin intermediate filaments to the cells membrane and bridging adjacent keratinocytes and allowing cells to with stand trauma. Structure: Cell membrane of 2 adjacent cells form a symmetrical junction with a central intercellular space of 30 nm containing a dense line . Plaques of electron dense material runs along the cytoplasm, parellel to the junctional region , thus 3 ultra structure bands are formedelectron dense band next to plasma membrane. Less dense band Fibrillar area
Main component of desmosomes in the epidermis : 1.Desmosomal cadherins 2.Armadillo family of nuclear and junctional protein 3.Plakin family Dermosmal cadherins - Transmembranous strctures . comprises mostly heterophillic association of Desmogleins (Dsg 1-3)and Desmocollins(Dsc 1-3) The intracellular part of these glycoprotein are attached to the keratin filament network via Desmoplakin, Plakoglobin, Plakophillin.APPLIED ASPECT-DSg 1:staphylococcal skin scalded syndrome and bullous imeptigo.
ADHERENCE JUNCTIONElectron dense transmembranous structure , engage with actin skeleton. Can associate with tight junction and desmosomes or exist separately. Characterized by 2 opposing membrane separated by approx. 20nm and are 0.20.5 m in diameter. Comprises 2 basic adhesion units : 1.Nectin afadin complex 2.Classical cadherin complex Nectin forms a structural link to the actin cytoskeleton via afadin (AF-6). Cadherins from complex with Catenins (-,-,p120catenin).
GAP JUNCTIONComprises clusters of intercellular channels known as connexons, Directly form connections between the cytoplams of adjacent keratinocyte and other cells. 13 different connexins are there. 6 Connexins 1 Connexon At plasma membrane connexons associate with other connexons to form a gap junction. Homotypic or heterotypic connexins are possible . FUNCTIONS OF GAP JUNCTION: essential for cell synchronisation, differentiation , cell growth and metabolic coordination of avascular organs including epidermis.
Tight junctionMajor regulators of permeability in simple epithelia. In skin:role in skin barrier integrity and maintain cell polarity. Principle structural protein of tight junction : Claudins(1-4) Other component transmembranous protein : Ig G- like family of junctional adhesion molecules and the occludin group of prot