Anatomical basis of cutaneous

structure & function

Speaker - Dr. Dibbendhu Khanra

Chairperson – Dr./ Prof. D. Bandopadhyay

Bob Marley died of malignant melanoma

Paris Hilton has atopic dermatitis, suffered from recurrent herpes labialis.

An american reporter had heat stroke while he was covering news in Sub-Saharan Africa

Painful leg ulcer in a DM patient

Young epileptic on valproate developed TEN

What is the function of

SKIN?Preservation and

reproduction of DNA

What are the requirements of skin for the protection and duplication of DNA?

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

Beauty may be skin–deep but skin has 4 layers

Cells of epidermis:1. Keratinocytes2. Langerhan’s cells3. Mast cells4. Melanaocytes5. Markel cells

Epidermis is not dead

Protein rich corneocytes

Lipid rich lamellar bodies

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

Dermo-epidermal junction

Vascularized dermis provides structural and nutritional support

-Vessels- ECM - Receptors and nerves- Erector pili muscle- Pilosebaceous unit- Hair

Collagen-tensile strength, -protects against trauma

Elastin -Elasticity-Resilience

Non-collagenous glycoproteins- facilitate cell-matrix interactions

Proteoglycan/glycosaminoglycan- hydration

Extracellular matrix

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

‘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)

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

TLRs have emerged as a major class of pattern recognition receptors in skin

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

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

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

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

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

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

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)

‘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

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

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

DNA damage by

UV ray

Loss of thermoregulation

Vascular damage

Skin failure with

massive TEWL

Compromised chemical and

immune barrier

Problems revisited

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