I. Introduction!A. Skin= largest organ of the body, has many functions incl.!1. Protection of loss of body fluid!2. Protection from microorganism and chemical invasion.!3. Heat production and heat loss (thermal homeostasis)!4. Sensing the envi!5. Protection from UV radiation!6. Production of vitamin D!7. Immune function!8. Blood pressure regulation!B. Skin has 2 subdivisions and specialized structures!1. Epidermis- a specialized stratified epithelium!2. Dermis- a dense irregular connective tissue!3. Specialized structures, hair, glands, nerves!4. Hypodermis- subcutaneous CT (not really part of skin), irregular CT!- Function: attachment of skin to underlying structures, padding/insulation/E storage, and conformation of external appearance of body!- Structure: connection is done by collagen and elastic tissue, padding/insulation/E done by fat (panniculus adiposus), body contours done by fat II. Epidermis: stratified squamous epithelium, has specializations for its functions A. Functions: protection from loss of body fluid, from invasion of noxious envi, from UV radiation, maintenance of epidermis, protection from abrasion, immune function!B. Structure:!1.Thick skin: hairless, plantar and palmar surface, 400-600 um thick!2. Thin skin: hairy, the remainder of the body, 70-150 um!3. Primary cells= keratinocytes --> go thru differentiation as they progress through successive layers!- Each layer= variable thickness, thickness of layer depends on thickness of skin!C. Epidermis consists of:!1. Stratum basale (germinativum)!- Made of cuboidal cells on basal lamina of dermal-epidermal junction!- Cells attached at base w/hemidesmosomes and lateral and apical surfaces w/desmosomes!- Site of intense mitotic activity, site of renewel of epidermal cells, ave. turnover= 15-20 days (faster turnover --> psoriasis)!- Hormones and cahlones play role in regulating skin turnover!- Vit D and A are regs!- Keratinocytes have R's for EGF (epidermal growth factor)!- Keratinocytes syn. transforming growth factor alpha --> role in autoreg. of skin growth/diff.!- Steroid hormones inhibit mitosis --> thinning of skin!- Keratinocytes have intermediate filaments= cytokeratins, are a component that increases in cytoplasmic density as cells mature in upper layers!- cytokeratins are differentially expressed thru the successive layers 2. Stratum spinosum- Polygonal-slightly-flattened cell layer, has spiny appearance due to crenated cell surface studded w/desmosomes --> tonofilaments gathered into bundles extend from these = tonofibrils in LM!- Increased surface area and many desmosomes --> tight contact between adj. cells and resist shearing forces from abrasion!- Structural proteins (laminin) aid in binding the keratinocytes!- Layer is thicker in areas prone to abrasion 3. Stratum granulosum!- Characterized by presence of granules!- Keratohyalin granules: !- basophilic, non-membrane, predom. type of granule, more abundant in thicker skin!- contain polysaccs and proteins (ex. histidine rich phospho-protein filaggrin)!- Filaggrins in successive layers binds tonofilaments into dense aggregates!- Keratinosomes: lamellar, membrane coated granules!- contain GAG and glyco-phospholipids, are secreted into extracellular space --> act as INTERcellular (between cells) cement = barrier to intracellular transport aka a seal (no tight/occuluding junctions in epidermis) - Submembranous protein envelope!- 10 nm thick, close to plasmalemma, made of highly cross-linked proteins (incl. keratolinin, involucrin, loricrin)!- crosslinked by transglutaminase!- function: structural integrity!- Stratum lucidum!- most apparent in thick skin!- flattened eosinophilic cells w/nuclei and organelles that have undergone dissolution, cytoplasm is predom. made of dense filaments - Stratum corneum (cornification)!- the intermediate filaments aggregated end to end --> tonofilaments --> tonofils aggregate w/help of filaggrin --> large bundles!- process starts in lower layers, happens more in stratum corneum!- cells lack identifiable organelles and hard to see cell membranes!- cell and products are dehydrated and exposed to air oxidation --> transforms the cell constituents!- cells are DEAD, OXIDIZED, DEHYDRATED - cells + their remnants = horny cells!- Desquamation= the final process of removing outer epidermal layer!- Not well understood, not process of abrasion!- Ichthyosis= disease where cornified layer not shed normally, 1 type lacking steroid sulfatase!- Hyp: liberation of lipolytic enzymes at outer epidermis D. Specialized cells!1. Melanocyte!A. Density highest in forehead and scrotum, constant throughout races!B. Produce a pigment= melanin!- Majority of people produce eumelanin (brown-black, hydroxy idoles)!- Some people (blonds and red heads) produce pheomelanin, a variant pigment (reddish-yellow, cystinyl-dopa)!- Melanins absorb electromagnetic radiation over broad range, assoc. w/their radioprotective role!- E absorption --> production of free radicals --> damaging, but cells will be desequamated!- High levels of radiation damage aren't protected --> increase in skin cancer!C. Epidermal-melanin unit: one melanocyte assoc. w/many keratinocytes!- melanocyte has long extensions that end in invaginations of the keratinocytes in stratum basal and stratum spinosum!D. Have NO desmosomes, only hemidesmosomes that attach to the basement membrane!- Melanoma cells= can metastasize!E. Melanin!- Precursor= tyrosine --(tyrosinase)--> converted to dopa --> more modifications --> melanin (polymer bound to protein)!- 4 stages in production:!1) Golgi derived vesicle (melanosome) containing tyrosinase, fine granular material, and filaments!2) Ovoid vesicle, parallel filaments w/melanin deposition!3) Increased melanin formation and little periodic fine structure visible!4) Dense melanin filled granule w/no tyrosinase activity!- melanosomes are transported via dendritic process and injected into keratinocytes, melanosome sits above nucleus= supranuclear!F. Sun tan induced by UV radiation (290-320 nm) and is from darkening preformed pigment by oxidation and accelerating production of more pigment by stimulating tyrosinase!G. Humans made a small amt of MSH (melanocyte stimulating hormone) in pituitary gland, but sequence is part of hormone ACTH!- MSH made by keratinocytes regulates melanin production!- Addison's disease: ACTH circulating levels are high --> hyperpigmentation 2. Langerhans cell A. Bone marrow derived cells, part of the mononuclear phagocytic
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