| 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 |
