anatomical basis of cutaneous structure and function, presented at cmc, kol on april, 2013
TRANSCRIPT
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Anatomical basis of cutaneous
structure & function
Speaker - Dr. Dibbendhu Khanra
Chairperson – Dr./ Prof. D. Bandopadhyay
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Bob Marley died of malignant melanoma
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Paris Hilton has atopic dermatitis, suffered from recurrent herpes labialis.
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An american reporter had heat stroke while he was covering news in Sub-Saharan Africa
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Painful leg ulcer in a DM patient
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Young epileptic on valproate developed TEN
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What is the function of
SKIN?Preservation and
reproduction of DNA
What are the requirements of skin for the protection and duplication of DNA?
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Skin is the largest organ in the body
In a 70-kg individual, the skin weighs over 5 kg
Covers a surface area approaching 2 m2
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Beauty may be skin–deep but skin has 4 layers
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Cells of epidermis:1. Keratinocytes2. Langerhan’s cells3. Mast cells4. Melanaocytes5. Markel cells
Epidermis is not dead
Protein rich corneocytes
Lipid rich lamellar bodies
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Corneocyte
Envelope proteins
Glutamyl lysyl isodipeptidase bond
Transglutaminase (TG 1-5)
Cytosolic precursors:-Involucrin- Small prolin rich protein
Granulocyte precursor:- Loricrin- Profilaggrin
Membrane proteins:- Plakins
Calcium
Lamellar body:
CeramideFatty acidCholestreolCholesterol esters
Protein-rich corneocytes are embedded within a continuous lipid-rich matrix
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Dermo-epidermal junction
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Vascularized dermis provides structural and nutritional support
-Vessels- ECM - Receptors and nerves- Erector pili muscle- Pilosebaceous unit- Hair
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Collagen-tensile strength, -protects against trauma
Elastin -Elasticity-Resilience
Non-collagenous glycoproteins- facilitate cell-matrix interactions
Proteoglycan/glycosaminoglycan- hydration
Extracellular matrix
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1.Terminal on the scalp and beard
2.Vellus on the majority of skin
3. Sebaceous on the chest, back and face
4. Apopilosebaceous in axilla and groin
Pilosebaceous Unit Glands of skin
Eccrine galnd: Sweating• Insensible and active• Thermal and mental• Sole, forehead and palm
Apocrine glands: Pheromones• Axilla• Nipples • Pubic/genital/circum-anal area• Lips and circumoral• Eyelids• Outer ear
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‘Barrier’ function of skin
TEWL
Lipid-rich envelope Keratin Sebum
Noxous agent
Intact stratum corneum
(Polar moleculesCan get thru lipid layer)
Keratin Immunity
Stretching
ECM
Trauma
Subcutaneous
fat(80% of fat is in
the subcutis)
Light/UV Ray
Thickened epidermis Stratum corneum Melanin(-brown/black =eumelanin -yellow/red =phaeomelanin)
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Skin: An immunological unit
1. Complements 2. Toll Like Receptors (TLR)3. Antimicrobial peptides (AMP)4. Macrophages
1. Antigen presenting cells (LC, DC)2. Lymphocytes3. Cytokines & Immunoglobulins
Innate immunity
Adaptive immunity
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TLRs have emerged as a major class of pattern recognition receptors in skin
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AMPs
• Cathelicidins• β-defensins• Adrenomedullin• Cystatin• Secretory protease inhibitor
- Broad spectrum of antimicrobial activity- Chemotactic for inflammatory cells- Promoting histamine release from mast cells - Adjuvant in enhancing antibody production- Increases the expression of TNF-α and IL-1
• Alarmins - Barrier repair and wound healing
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Langerhan’s cells – Survey the epidermal environment
Antigen presentation to T-cells
Short-term LCs developed from Gr-1hi monocytes under inflammatory conditions Long-term LCs arose from bone marrow in steady state and depend on Id2 LC reconstitution occurs in two waves: - Initial fast and transient wave of short-term LCs- Second wave of long-term LCs.
Dendrite surveillance extension and retraction cycling habitude (dSEARCH) allows an efficient antigen sampling
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Effector cells
1. Th1, Th2 cells (CD4)2. Tc CELLS (CD8)3. Treg cells4. NK cells (UV-induced immunosuppression )5. γ/δT cells (Leprosy, leishmnaiasis)6. DETCs (protect keratinocytes)7. B cells and Ig
Immune Response
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Circulation
1. Nutritional support2. Delivery of leucocytes3. Thermoregulation
- Adaptive immunity
2-way haematogenous system
1-way lymphatic system
Extensive subcutaneous venous plexus
hold large quantities of blood
dissipate heat from the surface of the skin
Arteriovenous anastomoses
prominent in areas exposed to maximal cooling
volar surfaces of the hands, feet, lips, nose, ears
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Interfacing with External and Internal Environments: Skin is a Communicating Organ
Communication via hormones
- ACTH in skin pigmentation- Vit D3 from epidermis- Pheromones from apocrine glands- MSH in appetite- Leptin from subcutaneous adipocytes
Cellular communication
- APC- Lymphocytes- Mast cells
‘Wired’ communication ‘Wire-less’ communication
Autonomic system (cholinergic)
1. Vasomotor functions
2. Pilomotor activity
3. Eccrine sweat gland secretion
Communication via cytokines
- Keratinocytes produce IL-1, IL-8, TGF-β- Mast cells produce TNF- Vascular endothelial cells produce IL-1β, IL-6
Sensory system Mechanoreceptors for touch• Skin:
- Rapidly adapting - Meissner’s corpuscle- Slowly adapting - Merkel’s receptor • Subcutaneous tissue :
- Rapidly adapting - Pacinian corpuscle, - Slowly adapting - Ruffini’s corpuscle, Thermoreceptor
- Cold receptors
- Warmth receptors Nociceptors
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Skin: conveyer of beauty & physical attraction; server of socio-sexual communication
The skin, by virtue of its visual appeal, smell and feel, has an important role in social and sexual communication in humans
On Beauty: Evolution, Psychological consideration and surgical enhancement: Allan & Dover
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Pheromones – myth or reality?
• Musky odour composed of 3-ol-
compound degraded by bacteria
• Kalogeraki & Beiber - Boys show
aversion to the odor of fathers but
feels attraction to the odor of
mothers (Oedipaus complex)
• Russel – Babies suck on only to
mother’s breast. Mother
unconsciously marks her baby with
a distinctive smell (Russel effect)
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‘A loss of normal temperature control with inability to maintain the core temperature, failure to prevent percutaneous loss of fluid, electrolytes and protein with resulting imbalance and failure of the mechanical barrier to penetration of foreign materials’
Examples• Thermal Burns• Stevens–johnson Syndrome, • Toxic Epidermal Necrolysis, • Graft-versus-host Disease
sometimes it fails!
Skin failure
Skin is so busy that
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Bioengineering and the skin
• TEWL measurement is used to assess the barrier function of skin• Transcutaneous oxygen tension (tcPo2) measurement to assess skin perfusion• Botox injection: decrease facial lines and sweating in disabling hyperhydrosis• Skin grafting• Finger-printing• Stem cells can be collected from skin• LC and DC capture protein antigens: Possible targets for vaccination
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What we have learned today?
1. Structural organization
2. Skin: Multitasking unit
3. Skin immunity
4. Skin failure
5. Skin bio-engineering
Mechanical barrier
Sensory unit
Pigmentory unit
Absorption
Temperature regulation
Endocrine unit
Immunological function
Elastic function
Sociosexual communication
Waterproofing Excretion of
waste
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DNA damage by
UV ray
Loss of thermoregulation
Vascular damage
Skin failure with
massive TEWL
Compromised chemical and
immune barrier
Problems revisited
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Thank you
What spirit is so empty and blind, that it cannot recognize the fact that the foot is more noble than the shoe, and skin more beautiful than the garment with which it is clothed - Michalangelo