Skin Physiology

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  • Created by: LBCW0502
  • Created on: 14-12-19 14:49
Describe the structure of embryonic skin (1)
Skin develops halfway through embryonic development. Early epidermis is a simple monolayer epithelium. Epithelial cells – connected, tall cells, sit on extracellular matrix, separation from connective tissue (cancer – epithelial layer puncture hole)
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Describe the structure of embryonic skin (2)
Dermis – contains connective tissue, fibroblast cells. Extracellular matrix. Basal monolayer, epithelium. Periderm – form surface between outside (uterus) and inside (embryo), flat cells, protect epidermal/stem cells
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Describe the structure of embryonic skin (3)
Expansion of monolayer epithelium of epidermis. Symmetric division of epithelial cells expand epidermis. Division horizontally, symmetric division, daughter cells divide, remain in monolayer, become skin cells. Skin needs to expand
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Describe the structure of embryonic skin (4)
Generation of suprabasal layer. Basal cell delamination and asymmetric cell division, generate new tissue layer - suprabasal layer. Build new layers of skin
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Describe the structure of embryonic skin (5)
Expansion of suprabasal layer. Stem cells stop attachments to basal lamina, movement upwards, move into space between periderm and basal monolayer, delamination (movement from basal lamina). Suprabasal layer – forms a protective layer, new layer
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Describe the structure of embryonic skin (6)
Differentiation of suprabasal layer. Stem cells divide vertically, top most daughter cell segregates from cells, moves into suprabasal layer. Intermediate layer dividing. Suprabasal layer gets bigger quickly, 1 day for skin layer to thicken, spreads
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Describe the structure of embryonic skin (7)
Cells stop dividing, start differentiating, start to produce proteins such as keratin. Hypodermis, epidermis
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Transition from embryonic skin to adult skin is characterised by what?
Terminal differentiation of epithelial cells in epidermis (adult epidermis has extra layers)
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Describe the structure of adult skin (1)
Stem cell layer, dermis, differentiating cells (terminal differentiation), stratum corneum (protective surface of skin). Terminal differentiation – stop proliferation, cells dying. Lose cells on the top layer of our skin, need to be replenished
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Describe the structure of adult skin (2)
Skin cells dividing, replenish stratum corneum layer with asymmetric divisions in stratum basale. Vertical division, cell divides, top daughter cell moves into upper layer (cell translocation), movement into stratum
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Final steps in epithelial cell differentiation are associated with what? (1)
Profound changes in cell structure. Terminal differentiation results in transformation into flat, anucleated corneocytes which populate the skin surface and slough off
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Final steps in epithelial cell differentiation are associated with what? (2)
From stratum basale to stratum corneum (asymmetric cell division, differentiation/cell translocation, cell death, cell loss)
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Final steps in epithelial cell differentiation are associated with what? (3)
Cells in stratum spinosum/granulosum undergo terminal differentiation – movement towards stratum corneum, lose nucleus. Stratum granulosum - skin cells extrude all fats/proteins that were inside the cell e.g. Golgi, ER, lipid rich internal membrane.
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Final steps in epithelial cell differentiation are associated with what? (4)
Get to the stratum corneum – skin cells covered with fats (which were from inside the cell) – skin becomes waterproof, barrier between outside and inside. When the nucleus is gone, skin cells become flat, volume of cell decreases
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Final steps in epithelial cell differentiation are associated with what? (5)
Papillary layer – capillaries, provide oxygen and nutrients to stem cells (epidermis layer), capillary loops. No blood vessels in epidermis
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Transition from embryonic skin to adult skin involves generation of sub-layers within which layer? (1)
Dermis. Ridges develop in the neonatal skin at the interface between the epidermis and dermis. Demis is sub-divided into a papillary layer and a reticular layer. Enriched for dermal fibroblasts that produce collagens (connective tissue)
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Transition from embryonic skin to adult skin involves generation of sub-layers within which layer? (2)
And elastic fibres of extracellular matrix which give the skin its elasticity
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Describe features of the reticular layer
Reticular layer – push down skin, elastic, lots of fluid filled space, lots of blood vessels
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Describe features of the dermis
Dermis contains fibroblast cells – free, move around a lot, complex structures, stretchy/contract, more motile cells, produce collagen (important for strength of skin), produce elastic fibres (elasticity)
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What happens in the skin during ageing?
Ageing – fibroblast stops producing collagen and elastic fibres (reduce strength and elasticity of skin)
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Transition from embryonic skin to adult skin involves the generation of what? (1)
The hypodermis - subcutaneous tissue with a high proportion of fat cells (adipocytes), acts as protective padding, insulator and energy reservoir. Skin appendages - hair follicles, extend into hypodermis. Sebaceous/sweat glands contained in dermis
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Transition from embryonic skin to adult skin involves the generation of what? (2)
Hypodermis – white, contains lots of fat cells, produces insulation for skin, source of fats for metabolism (generate energy for skin cells). Sebaceous gland – linked to hair follicle. Sweat gland in dermis
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Transition from embryonic skin to adult skin involves the generation of what? (3)
Hair follicle – one end found in hypodermis, other end coming out of the dermis
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What is homeostasis?
Maintenance of internal conditions in the body
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Which skin structures are necessary to mediate homeostasis?
Sweat glands and hair follicles
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Describe features of the skin appendages (1)
Sweat glands - coiled structure within outlet on epidermal surface. Merocrine/eccrine - general sweat glands. Apocrine - odorous sweat formed during puberty, respond to stress and sexual activity to release pheromones
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Describe features of the skin appendages (2)
Sebaceous glands - coiled structure with outlet on one side of hair follicle shaft, release oil onto skin (sebum also acts as antiseptic)
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Describe features of the skin appendages (3)
Sweat glands – coil structure, increase SA of tubing, large amount of sweat produced within a small volume of tissue (same for sebaceous gland). Opening of sweat gland on epidermis. Merocrine/eccrine glands – general sweat glands (born)
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Describe features of the skin appendages (4)
Apocrine – produce odorous sweat, respond to stress, sexual activity, produce pheromones (develop during puberty). Sebaceous glands – produce sebum, antiseptic, lubricates hair follicles.
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Describe features of the hair follicle (1)
Hair follicles develop in the embryonic skin soon after the suprabasal layer is established. Basal epidermal cells respond to signals from the dermis to create a hair placode
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Describe features of the hair follicle (2)
Hair follicle – originate from basal epithelial layer. Basal monolayer push down on dermis. Signals from dermis which activate pushing down of hair follicle. Dermis starts to regulate formation of hair follicles at an early process
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Describe features of the hair follicle bulb (1)
Hair bulb – contains epidermal cells and captures part of the dermis, important for hair follicles during adult age. Dermal papilla – at the bottom of the hair follicle, still gives signals to the rest of the epithelial cells in the hair follicle
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Describe features of the hair follicle bulb (2)
Regulatory cell region, matrix cells produce sac of where hair follicle forms, produce keratin, matrix cells continuous proliferation, outer cells of hair follicle important for hair follicle growing downwards
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Describe features of hair follicle regeneration (1)
Intermittent. Pull out hair follicle, including hair bulb – hair follicle cannot regenerate. Growth phase – anagen/hair growth, lasts 2-7 years. Transition phase – catagen/hair retraction – hair retraction. Resting phase – telogen/hair loss
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Describe features of hair follicle regeneration (2)
Formation of new bulb from remnants of ORS initiates growth of new hair follicle. Hair shaft leaves dermal capillary, hair follicle retracts out of dermis, sebaceous gland remains. Original hair pushed out, new hair grows
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Describe features of hair follicle regeneration (3)
Outer sheath – allows hair follicle to grow downwards. Stem cells in embryonic skin and adult skin
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How are hair follicles replenished? (1)
Using stem cells. Continuous cycles of cell division and differentiation build the epidermis in the embryo and replenish the epidermis in the neonate and adult. Skin stem cells only differentiate to form types of skin cells
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How are hair follicles replenished? (2)
GFP protein only made in basal cells. Columns of daughter cells over time. Stem cells in dermal layer - homeostatic mechanism
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How are hair follicles replenished? (3)
Homeostatic stem cell behaviour - ongoing replenishment of keratinocytes (ACD), balanced with replenishment of stem cells (SD). Skin expansion – during development, pregnancy.
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How are hair follicles replenished? (4)
Balance between vertical and horizontal divisions. Stem cells in hair germ, important for making new hair follicle. Cells in upper part of hair follicle – not active/growing. Sebaceous gland contains stem cells (not active/growing)
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What happens when the skin is damaged? (1)
Epidermal repair in adult is driven from stem cell niches in the hair follicle and associated sebaceous gland. Regional contribution to cell turnover. Hair follicle bulge - hair follicle recycling, isthmus region, sebaceous gland.
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What happens when the skin is damaged? (2)
Promoting Lgr6 transcription factor – expression of gene relating to certain cells. Take promoter of Lgr6 genes, add a fluorescent protein (expressed to determine which transcription factors are expressed in different stem cells)
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What happens when the skin is damaged? (3)
When there is a wound, a signal is sent to the hair follicle, stem cells in sebaceous gland proliferate, moves towards the wound for healing, stem cells stream from hair follicle to wound (heal/close wound to prevent infection/skin drying out)
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What happens when the skin is damaged? (4)
Fibroblasts can change shape, contract, activation of myofibroblasts (more contractile) helps to close wound, epithelial cells migrate to seal wound, stem cells in wound healing
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Outline the experiment to determine the healing process in the skin (1)
Experiment - fluorescent markers linked to DNA sequences which stimulate stem cell specific gene transcription incorporated into genome of mice, full thickness wound beyond hypodermis
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Outline the experiment to determine the healing process in the skin (2)
Confocal microscopy used to visualise fluorescent stem cells as they stream into wound
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What was the conclusion from the experiment?
Wound response delivers signal to hair follicle/sebaceous gland and activates quiescent stem cells which proliferate. Stem cell progeny collectively move into wound and participate in wound healing
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What are the four phases of wound healing?
Haemostasis, inflammation, proliferation of granulation, remodelling or maturation
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What are the main functions of the skin? (1)
Principal barrier between the outside and inside (physical - UV radiation, microbial - bacteria, fungus, chemical - allergens, irritants, prevents entry of chemicals but also prevents loss of water)
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What are the main functions of the skin? (2)
Regulation of body temperature (regulation of blood flow, sweat, insulation - cutaneous fat). Enables sensation of touch and pain (mechanosensation)
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What are the main functions of the skin? (3)
Stratum corneum acts as barrier to prevent water loss. Creates barrier to chemicals/microbes, buffets mechanical stress, prevents desiccation
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Describe features of filliagrin (1)
Couples keratin proteins together, orderly bundling of keratin filaments, flattens corneocytes. Provides a stable barrier. Mouse model - LOF, fillagrin, dry flaky skin, human disease/mutation - atopic dermatitis, ichthyosis vulgaris
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Describe features of filliagrin (2)
LOF keratin-10 delicate epidermis - hyperkeratosis
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Describe features of transglutaminase
Protein cell envelope - cross linking of involucrin and loricrin by transglutaminase enzyme. Stable water-tight barrier. Mouse model - mutations in transglutaminase, LOF loricrin increases suscep to mechan stress. Human disease - lamellar ichthyosis
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Describe features of the lipid cell envelope in the stratum granulosum (1)
E.g. golgi, progressively changes to lamellar bodies which fuse with the plasma membrane and exocytose their contents to EC space as parallel arrays of lipids. Forms a water tight barrier. Human disease/mutation - essential fatty acid syndrome
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Describe features of the lipid cell envelope in the stratum granulosum (2)
Disturbed permeability, susceptible to bacterial infection, delay in wound healing, alopecia lamellar ichthyosis type 2
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State features of keratins
Keratins – cytoskeletal proteins, intermediate filaments, generate stability in cell structure. Keratins also found in hair. Corneocytes flatten – lose nucleus, keratins also help to flat corneocytes, keratin binds to desmosomes
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Which types of cell junctions in the nucleated suprabasal layers contributed to barrier formation?
Desmosomes, tight junctions and adherens junctions
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Describe features of adherens junctions (1)
Enables TJ formation. Mouse model - LOF E-cadherin die perinatally from water loss. Cells able to move past each other, ensure cells stick together, important in skin (enable TJ to form), found in early differentiating cells
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Describe features of tight junctions (2)
Tight junctions – junctional fence creates barrier, help to retain water. Mouse model - LOF claudin-1 loss of TJ in SG mice die at birth from water loss. Human disease/mutation - claudin-1 mutation, neonatal sclerosing cholangitis
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Describe features of desmosomes (1)
Desmosomes – link corneocytes together, contains keratins to link junctions/maintain strength and barrier/stability. Desmoglein – part of the desmosome junction (lost – results in susceptibility towards bacterial infection)
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Describe features of desmosomes (2)
Continous sheet of corneocytes. Mouse model - LOF desmoglein desiccation and bacterial infection. Human disease/mutation - LEKT1 deficiency autoantibodies to desmosomal proteins leads to Pemphigus vulgaris
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What happens when the skin barrier isn't formed properly?
Gives rise to inherited skin disorders and inflammatory skin disease
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Describe features of epidermolysis bullosa - inherited skin disease (1)
Often blisters form at the site of friction/rubbing. Chronic wounds don't heal well. Epidermolysis bullosa simplex - human gene mutations in Keratin5 and Keratin14, stratum basale-specific Keratins - autosomal dominant
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Describe features of epidermolysis bullosa - inherited skin disease (2)
Junctional epidermolysis bullosa - human gene mutations in laminin and collagen, autosomal recessive
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Describe features of epidermolysis bullosa - inherited skin disease (3)
Epidermolysis bullosa simplex – sensitive skin, poor wound healing, blistering from rubbing, chronic wounds, human gene mutations in keratin 5 and 14 (found in basal layer of stratum, important for generating suprabasal layer
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Describe features of epidermolysis bullosa - inherited skin disease (4)
Basal layer not formed properly/cells not strongly connected, suprabasal layer not strong/formed properly), skin layers likely to come apart between basal layer and basal membrane
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Describe features of epidermolysis bullosa - inherited skin disease (5)
Junctional epidermolysis bullosa – weak basal lamina, lack of collagen, skin layers not strong enough, skin layers come apart
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Describe features of inflammatory skin disease - blistering disease (1)
Dry scales of scale like crusts on skin - pemphigus vulgaris, toxic epidermal necrolysis, contact dermatitis (can be life threatening of large parts of the body are affected)
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Describe features of inflammatory skin disease - blistering disease (2)
Disruption to ongoing cell division/differentiation leading to reduced skin permeability and subsequent inflammation. Immune response to bacterial infection results in inflammation which disrupts ongoing cell division
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Describe features of inflammatory skin disease - blistering disease (3)
Differentiation leading to changes in skin permeability. • Junctions important for stability of skin layers. Possible issue with junctions – not tight, spaces between cells become leaky, cause inflammation
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Describe features of epidermal melanocytes (1)
Produce melanin pigment (protection against UV). Neural crest derived, migrate into skin during foetal development, stellate cells mainly in basal layer (1 melanocyte for every 5-10 keratinocytes), numbers similar between races but activity varies
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Describe features of epidermal melanocytes (2)
Melanin helps protect against damage by absorbing UV before it reaches the deeper layers of epidermis and dermis
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Describe features of epidermal melanocytes (3)
Lots of processes which wrap around stem cells and covers suprabasal cells (stellate cells), produce melanin protein (protection against damage, absorbs UV before it reaches deeper layers, prevent DNA damage in stem cells)
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Describe features of epidermal melanocytes (4)
Damaged DNA in dividing stem cell, daughter cells can inherit mutation/damaged DNA, rapid division (cell proliferation unregulated, tumour growth on skin)
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Describe features of immune surveillance in the skin (1)
Skin is the primary interface between the body and outside environment. First line of defence against microbial pathogens and trauma
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Describe features of immune surveillance in the skin (2)
Innate immune surveillance - Langerhans cells and epithelial keratinocytes release antimicrobial peptides and cytokines, recruit immune cells locally or from blood. Dermis contains dendritic/APC cells and T memory cells
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Describe features of immune surveillance in the skin (3)
Macrophages, move through skin (despite tight junctions, cell connections), engulf bacteria, signals to other cells in dermis and blood vessels, activate immune response
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Describe features of sensory perception in the skin (1)
Embryo - innervation of skin by neuronal processes (afferent projections), cell bodies coalesce to form ganglia peripheral NS. Innervate dermis and epidermis, free endings in dermis which can penetrate basal lamina, innervate epidermal cells (Merkel)
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Describe features of sensory perception in the skin (2)
Sensory nerve fibre found at base of each hair follicle - movement of single hair shaft. Nerve processes also linked to sensory proteins, stimulation, produce signal which is transmitted along nerve as electrical impulse
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Describe features of sensory perception in the skin (3)
Temperature receptors - nociceptive C-fibre, (non)-peptidergic, control blood flow. Pain receptors - nociceptive (non)-peptidergic. Itch receptors (cutaneous pruiceptive)
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Describe features of sensory perception in the skin (4)
Skin connected to CNS, cell bodies of neurones sit outside CNS in DRG, send axon out to innervate the skin, free nerve endings in the skin, bipolar neurones, Merkel cells, nerve endings linked to hair follicles (allow movement of hair follicle)
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Describe features of mechano-reception in the skin (1)
Meissner corpuscle - light touch/pressure found in dermal papillae. Pacinian corpuscle - coarse touch/pressure located in dermis. Merkel cell - epidermal cell located in pit of epidermal/dermal ridges which is touch sensitive, elicits afferent (CNS)
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Describe features of mechano-reception in the skin (2)
Response in associated nerve endings. Ruffini organ – recognises stretching of the skin, nerve endings linked together. Lots of mechanoreceptors found on fingertips
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State features of homeostasis and temperature regulation
Skin acts as the sensory system and effector. CNS acts as control centre part of the ANS - sympathetic branch. Skin acts as sensor, signal to hypothalamus, integration and response, response via motor neurones to effector (organ/hair follicle/glands)
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Describe features of thermoregulation - blood vessel innervation
Blood vessels in hypodermis, insulation with fat, capillaries in epidermis (O2 to cells, also temperature regulation). Vascular system innervates dermis and not epidermis
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Describe features of thermoregulation - heat exchange regulates body temperature (1)
Normal body temperature is maintained by regulating heat gain and loss to the outside. Heat loss is regulated by altering blood flow through the capillaries in dermal papillae. Heat exchange occurs via convection (air flow over skin) and radiation
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Describe features of thermoregulation - heat exchange regulates body temperature (2)
Cells in hypothalamus monitor temperature of blood flowing through capillaries (core temperature) and stimulate thermoregulatory processes. Vasodilation also stimulated by local production of bradykinin
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Describe features of thermoregulation - heat exchange regulates body temperature (3)
Cold - more blood flow in hypodermis, less on surface. Hot - less blood flow in hypodermis, more on surface
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Describe features of thermoregulation - arrector pili muscle of hair follicle and sweat (1)
Ribbon of smooth muscle linked via connective tissue sheath around the hair follicle to papillary layer of dermis. Muscle contraction elevates hair (goosebumps). Induces insulated layer of air to reduce heat loss
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Describe features of thermoregulation - arrector pili muscle of hair follicle and sweat (2)
Sweat - release of sweat regulates body temperature by evaporation, excretion of organic wastes (urea) in sweat
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Describe features of skin, neural circuits and regulation of temperature homeostasis (1)
Sweating is stimulated by a skin specific neural circuit - evaporation. Temperature receptors - warm sensor subsystem, cold sensor subsystem, many in face. Activate sensory afferent nerves, merge on cranial ganglia and integrate signal
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Describe features of skin, neural circuits and regulation of temperature homeostasis (2)
Sent into brain stem and onto hypothalamus/thalamus in brain. Sensory afferents input into dorsal root ganglia in lower trunk, signal sent into lumbar region of spinal cord and onto thalamus/hypothalamus
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Describe features of skin, neural circuits and regulation of temperature homeostasis (3)
Neural pathways from brain to skin. Input from temperature receptors in skin is integrated with information about internal body temperature, hypothalamus generates major output signal via efferent nerves to sweat glands
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Describe features of skin, neural circuits and regulation of temperature homeostasis (4)
Fine control over body temperature achieved by an integration of different signals into/from different brain regions. Feedback control of the different inputs is important for homeostasis
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Definitions
Lecture Slides
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Card 2

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Describe the structure of embryonic skin (2)

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Dermis – contains connective tissue, fibroblast cells. Extracellular matrix. Basal monolayer, epithelium. Periderm – form surface between outside (uterus) and inside (embryo), flat cells, protect epidermal/stem cells

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Describe the structure of embryonic skin (3)

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Describe the structure of embryonic skin (4)

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Describe the structure of embryonic skin (5)

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