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Skin
Organisation of the Body
| Question | Answer |
|---|---|
| Skin | Major barrier to the external environment Largest organ in the body Continuous with mucosae of alimentary, respiratory, urogenital tracts Performs a number of major functions |
| Functions of the skin | Interaction with the environment Protective - mechanical, chemical etc Interactive - friction, temp control Immune surveillance and pathogen block Synthetic - vit D, GF Sense organ Communication with others Absorptive |
| Three layers of the skin | Epidermis Dermis Hypodermis (subcutis) |
| Layers of the epithelium | Stratum corneum Stratum Lucidum Stratum granulosum Stratum spinosum Stratum basale - rete ridges |
| Stratum basale | Renews epidermis every 25-30 days Contain stem cells and daughter cells that divide to produce keratinocytes and other epidermal cell types Low columnar/cuboidal cells expressing specific keratin isoforms - aggregate to form tonofilaments |
| Junctional complexes in epithelia | Contains tight junctions in the upper layers for impermeably and to block GF diffusion Mainly desmosome and hemidesmosomes Can see the importance of intermediate filament structures by diseases affecting them |
| Hemidesmosomes | Connect the basal cell layer to the basement membrane Contains integrins and selectins, which interact to hold cells to the membrane Plaques on the cell membrane anchor intermediate filaments (tonofilaments) |
| Other cells in Stratum Basale | Melanocytes Merkel cells Langerhans cells All appear with a clear cytoplasm |
| Melanocyte function | Melanin formed in melanocytes and its different forms are responsible for different hair and skin colours Melanocytes form melanin in melanosomes Melanosomes are transferred along cytoplasmic processes into cytoplasm of stratum basale and spinosum |
| Types of melanosome | Eumelanosomes Pheomelanosomes - more red and yellow due to increased sulphur content |
| Defects of melanosome | Defects in tyrosine pathway in both - albinism e.g. tyrosine negative oculocutaneous albinism Most common form of albinism (OCA2) affects P gene, which encodes a scaffold protein for Tyr, TYRP1/2 in eumelanosomes |
| What are melanosomes | Modified lysosomes Defects in lysosomal protein trafficking will lead to defects in pigment granules in humans (OCA) Same in mice and flies |
| Melanocyte development | Derivatives of neural crest cells that migrate around the body Defects in neural crest cell development and migration produce pigmentation defects e.g dominant piebald trait from mutation of receptor tyrosine kinase kit |
| Skin colour - Abnormalities | Stimulation of melanocyte expansion by UV Café-au-lait spot - increased melanin associated with underlying disease in some cases Naevus - benign tumour of melanocytes Malignant melanoma - irregular edges, multiple shades and asymmetrical |
| Stratum Spinosum | High levels of keratin expression Prickles - cellular projections that permit attachment to neighbouring cells via desmosomes Spaces are cytoplasmic processes of melanocytes and Langerhans cells |
| Stratum Granulosum | High levels of keratin with no new production Basophilic granules - proteins containing sulphur rich AAs for linking e.g. involucrin and loricrin Small keratinosomes - water repellent lipids |
| Cornified cell envelope | Contents of keratinosomes and keratinohyaline granules together with tonofilaments form mature cross linked keratin under the keratinocyte plasma membrane |
| Stratum Corneum | Reminents of dead keratinocytes including desmosomes, tonofilaments and cornified cell envelope Determines the thickness of the skin Outer layers slough off at 1.5g a day |
| Skin thickness | Regional variation - sole of the foot is thick whilst lack of the had is thin Variation in thickness of cornified layer, some variation in the dermis Variation with age, stretching (pregnancy) and hormonal changes (excess cortisol - thinning) |
| Fingerprints (Papillary ridges) | On palms and soles Parallel curved arrays Epidermal ridges Sweat glands open onto apex Inherited, stable through life Provide grip and are a sensory organ - receptors under epidermis in dermal ridges |
| Nails | Specialisation of cornified layer Dorsal aspect of terminal phalanx Keratin filled squames in layers Comprise nail plate, proximal and lateral nail folds, nail bed Nail appearance is a diagnostic tool Nail plate dips into epidermal layer (nail folds) |
| Vohwinkle syndrome | Dominant connexin 26 mutations Leads to deafness and severe keratosis (epidermis thickens and can amputate the digit) Causes abnormal gap junction formation- involved in keratinisation |
| Lamellar icthyosis | Recessive transglutaminase 1 mutations Sever scaling of the skin Failure to crosslink proteins in the outer layer of skin |
| Dystrophic Epidermis bullosa | Dominant mutations in collagen VII gene, leads to blistering and scarring The desmosomes/ hemidesmosomes do not form so dermis and epidermis separate |
| EB simplex | Dominant mutation in keratins 5 and 14 Recessive mutations in plexin Can also lead to muscular dystrophy (involved in attachment of desmin to sarcolemma) |
| Junctional EB | Recessive mutations in integrin alpha 6 and beta 4 Pyloric atresia JEB - intestinal blistering and congenital skin absence e.g. heels and legs Mutations in laminin 5 (Herlitz JED - usually dies from respiratory distress) |
| Pemphigus | Anti desmoglein autoantibodies Skin blistering disease as cells detach Antibodies to both Dsg1 and 3 (major component of deeper desmosomes) - pemphigus vulgaris with deep blisters |
| Development of skin | Epidermis - ectoderm Dermis -mesodermal <2 months - ectoderm forms periderm and epidermis proper 7-8 weeks - presumptive melanocytes and Langerhans cells migrate in and fine hair follicles form 4 months - sweat gland bud 5 months - sebaceous glands |
| Basal cell proliferation | Regulated by signals from dermis (FGF7) and epidermis (TGF-alpha) TGF alpha may be upregulated in psoriasis - scaly skin Presumptive hair forming cells in mouse epidermis make Shh to instruct dermis to induce epidermal differentiation |
| Dermis | Upper layer - papillary dermis, a fine network of collagen and elastin with small blood vessels, nerve endings and fibres Lower more extensive layer - reticular dermis, dense collagen (type 1) and long thick elastic fibres Loss of elastin - cutis laxa |
| Blood supply | Cutaneous plexus - hypodermis/dermis junction Subpapillary plexus - upper dermis, superficial appendages Arteriovenous shunts - thermoregulation, especially dermis of extremities - can divert blood away during the cold |
| Nerves of the skin | Merkel cells (epidermis basal layer) - touch Free nerve endings in dermis - pain, itch and temperature (may contact Merkel cells) Meissner's corpuscle - dermis for light touch Pacinian corpuscle - deep in dermis for course touch, vibration and tension |
| Hypodermis (Subcutis) | More variable layer Adipose tissue separated by fibrocollagenous septa Food store, thermal insulator and shock absorber Thicker in certain areas to protect underlying organs |
| Skin appendages | Pilosebaceous apparatus - hair follicle/shaft and accessory structures Glands - eccrine and apocrine |
| Hairs | Variable levels in different parts of the body Hair shaft surrounded by a hair follicle an epidermal downgrowth, which extends into the dermis and hypodermis Hair shaft grows from hair bulb containing dividing epithelial cells, surrounds dermal papilla |
| Pilosebaceous unit | Hair follicle Shaft Arrector pili muscle Sebaceous glands |
| Arrector pili muscle | Smooth muscle Sympathetic control Thermoinsulation in hairy animals and goose bumps |
| Sebaceous units | Oily sebum filling space vacated by inner root sheath breakdown Release lipids by cellular degeneration (holocrine) Waterproofs and moisturises Found independently of hair follicles in regions adjacent to body tracts e.g. lips Androgen stimulation |
| Eccrine glands | Virtually ubiquitous Simple coiled tubular glands in superficial part of subcutis - sweat Cholinergic sympathetic control Thermoregulation and excretion |
| Apocrine glands | Breasts, axillae and genital regions Produce viscous milky secretion - foul odour when metabolised by commensal bacteria Adrenergic sympathetic control and female sex hormones Scent organs in other mammals |
| Common diseases of skin | Psoriasis - abnormal immune response leads to excess skin formation and scaling Acne - hair follicles blocked by sebum (can be infected) Eczema - excessive immune response -itchy rash and scaling may be at site of contact or a general response Vitiligo |
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