Biomedical Cell Biology: Skin PDF

Biomedical Cell Biology Skin Dr J Ashworth Structure of Skin Human skin consists of 4 distinct regions: epidermis basement membrane zone dermis subcutaneous layer Structural Organisation of Skin...

Biomedical Cell Biology Skin Dr J Ashworth Structure of Skin Human skin consists of 4 distinct regions: epidermis basement membrane zone dermis subcutaneous layer Structural Organisation of Skin Epidermis Arises from dividing keratinocytes in basal layer of skin. Cells migrate through 4 layers: basal cell layer (stratum basale) prickle cell layer (stratum spinosum) granular cell layer (stratum granulosum) keratinised layer (stratum corneum). As cells pass through granular layer, they start to terminally differentiate into keratinized squames, losing their nuclei and cytoplasmic organelles. Keratinised squames eventually flake off as new cells move up through the epidermis. Basement Membrane (basal lamina) Separates epidermis from the dermis. Complex structure made of proteins such as collagen, integrins and laminin. Cells in basal layer are attached to the basement membrane via hemidesmosomes.  Dermis Supports and nourishes the epidermis. Contains extracellular matrix (ECM) composed of collagen, elastin and proteoglycan ground substance. Collagen fibres provide tensile strength to prevent over-stretching and tearing. Elastin fibres maintain skin elasticity and recoil. Ground substance (glycosaminoglycans) maintain skin turgidity by attracting and holding water. ECM is continuously remodelled (degraded and re-synthesised). Contains vessels (blood & lymphatic) and appendages (sweat & sebaceous glands, hair follicles). Subcutaneous Layer Provides support for the dermis. Consists of adipose and loose connective tissue and contains vessels (blood & lymphatic) and nerves that supply the skin. Contains resident inflammatory cells (macrophages) and fibroblasts.  Function of Skin Skin protects against microbial or parasitic infection: Provides impenetrable barrier to most microbes & parasites. Sebum from sebaceous glands protects against infection. Epidermal cycling of keratinocytes provides effective mechanism to remove infected cells. Skin is waterproof: Stratum corneum is a semi-permeable barrier that maintains skin moisture and prevents desiccation. Sebum from sebaceous glands protects against desiccation.  Skin protects against mechanical damage: Adipose layer absorbs mechanical impact/shock energy. Keratin of epidermis protects against minor cuts & abrasions. Epidermal cycling removes cells that become physically damaged. Skin protects against chemical and osmotic damage: Semi-permeable barrier of skin prevents penetration of many environmental agents. Epidermal cycling removes cells that become contaminated. Skin protects against thermal and photic damage: Adipose layer insulates underlying tissues and organs. Hair and sweat production are important in thermoregulation. Melanin in melanocytes absorbs UV radiation from the sun. Epidermal cycling removes cells that become physically damaged. Other Functions: Adipose tissue acts as an energy (fat) store. Skin is an important source of vitamin D production. Ageing in Skin EXTRINSIC AGEING Environmental damage to skin over a lifetime (mainly from photoageing). INTRINSIC AGEING Age-related decline in cellular proliferation, biosynthetic activity and tissue organisation. Studying Intrinsic Ageing Processes in Human Skin: Intrinsic ageing is best studied in sun-protected skin to reduce the influence of photoageing: e.g. Biopsies taken from arm-pits or buttocks. Intrinsic Ageing in Skin Epidermis Decrease of up to 50% in epidermal turnover rate. Increased susceptibility to cutaneous infections due to reduced epidermal turnover rate. Cells in stratum corneum often display parakeratosis, characterised by nucleus retention. Stratum corneum becomes less effective at resisting penetration by chemical or infectious/parasitic agents. Xerosis (dry scaling of skin) is common due to altered lipid content in the stratum corneum.  Dermis Thickness declines (1% decrease in collagen/year of adult life). Decline in number and biosynthetic activity of dermal fibroblasts. Skin wrinkling results from a decline in collagen & elastin fibres. Loss of structural fibres leads to reduced strength & elasticity. Structural organisation becomes irregular (randomly- oriented collagen & fragmentation of elastin fibres). Flattening of the dermoepidermal junction (fewer interdigitations) increases propensity for layer separation following trauma/oedema. Linear decrease in ground substance, resulting in reduced water- holding capacity. Subcutaneous Layer Re-distribution of adipose tissue: Atrophy particularly seen on face, dorsal hands and shins  contributes to skin sagging and folding. Hypertrophy in some areas, particularly waist of elderly males and thighs of elderly women.