Handout Fisiologi Kulit

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SKINPHYSIOLOGYDr. Trinovita Andraini, Mbiomed

Dr. Imelda Rosalyn Sianipar, MBiomed

Department of physiology, FMUI

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OUTLINE

Introduction of the integumentary system

Function of the skin

Effect of the environment to the skin health

Relation of the integumentary system with othersystem

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THE INTEGUMENTARY SYSTEM

Integumentary System

(inte = whole; -gument = body covering )

Two major components:

Cutaneous membrane / skin

Accessory structure: hair, nails, & multicellular exocrine

glands

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SKIN(CUTANEOUS MEMBRANE)

Largest organ of the body, both surface area &

weight

In adults,

covers an area of about 2m2

weighs 4.55 kg (16% of total body weight)

Has 2 components: Epidermis

Dermis

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SKIN(CUTANEOUS MEMBRANE)

The epidermisis the ectodermally derived

outer layer composed of keratinized stratified

squamous epithelium.

The dermisis the mesodermally derived

layer of dense irregular collagenous

connective tissue that underlies and

interdigitates with the epidermis.

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Skin Structure

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ACCESSORY SKIN STRUCTURES

1. Hair and hair follicles

2. Smooth muscle arrector pilli

3. Cutaneous glands

4. Nails

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HAIR AND HAIR

FOLLICLE

- Has minor protective

function

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GLANDS OF THE SKIN

Major glands:

Exocrine glands

Consist of:

1. Sebaceous glands(oil)

2. Sweat glands

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GLANDS IN THE SKIN

Skin2 types of exocrine glands:

Sebaceous glandsand sweat glands

Sebaceous (oil) glandsoily lipidsecretionsebuminhibits bacteriagrowth, lubricates and protects thekeratin of the hair shaft and conditionsthe surrounding skin.

Sebaceous follicles (not associated withhair follicles) discharge sebum directlyonto the epidermis: on the face, back,chest, nipples and external genitalia

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GLANDS IN THE SKIN

Sweat glands/ sudoriferous glands:

apocrine sweat glands and merocrine

sweat glands.

Apocrine sweat gland

- Armpits; around the nipples and pubic region

- Secretion: sticky, cloudy and odorous

- Secreting at pubertynutrient source for

bacteria

- Controlled by nervous system and circulating

hormones11

GLANDS IN THE SKIN

Merocrine (Eccrine) sweat glands

- More numerous than apocrine (adult : 2-5 million) palms, soles and forehead >>

- Sweat produced = sensible perspiration

- 99% water + electrolites (NaCl), organic

nutrients, peptide (AntiBiotikproperties),waste products.

pH 4.0 -6.8

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GLANDS IN THE SKIN

Functions of merocrine sweat glands

- Cooling the surface of the skin

- Regulated by neural and hormonal

- Excreting water and electrolytes (+

ingested drugs)

- protection from Environmental Hazards

* Dilution harmful chemicals; inhibition growth

of microorganisms by flushing and action ofdermicidin

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GENERALFUNCTIONOFTHEINTEGUMENTARYSYSTEM

ProtectionExcretion

andAbsorption

SensationMaintenance

of BodyTemperature

Synthesis ofVitamin D3

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GENERAL FUNCTION

B. Excretion and Absorption

- Sweat excretion

- Absorption of water soluble substances,

certain lipid soluble materials, certain

drugs and gases

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GENERAL FUNCTION

C. Sensation of touch, pressure, pain

and temperature stimuli

Variety of nerve endings and sensory

receptors are distributed in the

epidermis and dermis

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GENERAL FUNCTION

D. Maintenance of body temperature

- Thermoreceptors

- Sweat production and evaporation

- Alterations in cutaneous blood flow

conserve or release heat

* Local control

* Neural control (primary

determining factor)

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GENERAL FUNCTIONMAINTENANCEOFBODYTEMPERATURE

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GENERAL FUNCTION

E. Synthesis of vitamin D3

- Action of UV rays in sunlight to the molecule inthe skin.

- The role of liver and kidneys to produce the

most active form of vitamin D3

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SYNTHESISOFVITAMIND3

Guyton&Hall. 2011

7 dehydrocholesterol

(in the skin)

Cholecalciferol (Vit. D3)

UV Radiation

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PROTECTIONFUNCTIONOFTHESKIN

The chief function of the skinto form a barrier between

the external environment and the internal milieu of the

host

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SKIN

HOSTILEEXTERNAL

ENVIRONMENT

INTERNALMILIEU OF THE

HOST

PROTECTIONFUNCTIONOFTHESKIN

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The skin barrier prevents exessive water loss (inside-outside barrier) and entry of harmful substance from

the environment (outside-inside barrier)

Fitzpatrick Dermatology, 2008

Factors that play role in the protectionfunction of the skin: Stratum corneum

natural moisturizing factors (NMF) in the skin

Oily sebum

Pigment melaninprotection to UV radiation

Acidic pH of perspiration

Epidermal langerhans cells and macrofages in thedermis

Production of antimocrobial peptides (AMPs) byviable cell in epidermis 23

STRATUMCORNEUM

Localized in the outerepidermal layer

The thickness is 10-20 um

Is composed of:

Corneocytes, which are arranged in a scaffold-like

lattice, bound together by involucrin

Extracellular lipid matrix

water impermeability

The impermeability of water of the skin is 1000

times higher than that of other membranes of

living organisms24


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EPIDERMIS

Epidermis is terminally differentiated stratified

squamous epithelium

The mayor cell type is keratinocyte.

Consist of: Stratum basale, stratum spinosum,

stratum granulosum, stratum corneum

Epidermis is in a constant state of self replacement

Keratinizationis the transformation process ofstratum basale cells into stratum corneum cells

The time from cell division to shedding from the

stratum corneum: 28 days

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EPIDERMALLAYER

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KERATINIZATION

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At the stratum basale, keratinocytes stem cells devideinto daughter cells, which are displaced outward

Keratinocytes differentiate through successive overlyinglayers to enter the stratum corneum

During differentiation, keratinocyte on the Stratumspinosum and granulosum generate lamellar bodiescontaining lipid

During the terminal differentiation, lipid matriks from

lamellar bodies spread over to the intercellular domainsof stratum corneum and form a bilayer stucture

Keratinocytes die, apoptosis and their cellular organelles,nuclei and cytoplasm disappearcorneocytes

The cells appear flatened and the keratin filaments(involucrin) align the corneocytes into disulphide crosslinked macrofibres.

KERATINIZATION

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Denda. Skin barrier function as a self-organizing system. Forma, 2000. 15:227232


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EXTRACELLULARLIPIDMATRIXINSTRATUMCORNEUM

Consist of:

50% Ceramides

25% cholesterol

15% free fatty acid

Phospholipid

This lipid is secreted from lamellar bodies (which

found in keratinocyte at spinosum/granulosum

layer).

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FORMATIONOFTHEEXTRACELLULARLIPID

MATRIXONSTRATUMCORNEUM

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Feingold. The role of epidermal lipids in cutaneous permeability barrier homeostasis. J. Lipid Res. 2007. 48: 25312546.

EXTRACELLULARLIPIDMATRIXMEDIATE

PERMEABILITYBARRIERFUNCTION

provide an impermeable barrier for the passage of

water out of the stratum corneum and the

prevention of the natural moisturizing factors

(NMF) from leaching out of the surface layers ofskin.

Ceramidestrap water molecules in their

hydrophilic (water attracting) region

Glycerol (from breakdown of phospholipid byPLA2)water holding agentkeep stratum

corneum hydratedcrucial for smooth and flexible

skin 31

EXTRACELLULARLIPIDMATRIXMEDIATE

PERMEABILITYBARRIERFUNCTION

Cholesterol: plays an important role in regulating

desquamation

FFAacidification of the stratum corneum (pH 5-

5,5)important for enzymes activities, eg. Beta

glucocerebrosidase and acidic sphyngomyelinase

If ph >

Beta glucocerebrosidase activities is reducedthe

processing to form ceramide is impairedabnormalities

of extracellular lipid membranesdecreased

permeability barrier function

activities of protease increasescorneosytes desquamation

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AFFECTOFENVIRONMENTTOSKINBARRIERSKINBARRIERHOMEOSTASIS

Skin barrier function has ability to adapt to theenvironmentsense the environment changeand reorganizes its function to adapt the newenvironment

Low humidity, mechanical assault, chemicalassault (eg. treatment with an organic solvent ordetergent) stratum corneum barrier functiondemagehomeostasis process accelerated:

Lipid synthesis

Lipid processing

Acceleration of exocitosis of lamellar bodies

Barriers recovers to its original level 33

REGULATIONOFPERMEABILITYBARRIERREPAIR

Calcium gradient

In normal condition, there is high level extracellular

calcium in the upper epidermis surrounding the

stratum granulosum cells

After barrier disruptionincrease water movement

through the compromised stratum corneum carries

calcium outward toward the skin surfacereduction

calcium concentrationprimary signal to induce

lamelar bodies secretion

Cytokines: IL-1, IL-6, TNF alfarapidly release

after barrier disruptionregulating permeability

barrier34

REGULATIONOFPERMEABILITY

BARRIERREPAIR

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Feingold. The role of epidermal lipids in cutaneous permeability barrier homeostasis. J. Lipid Res. 2007. 48: 25312546.

EFFECTOFENVIRONMENTTONATURAL

MOISTURIZING FACTORS(NMF) INTHESKIN

natural moisturizing factors (NMF) are present

in the stratum corneum:

free amino acids

Other physiological chemicals such as lactic acid,

urea and salts

are responsible for keeping the skin moist and

pliable by attracting and holding water

The water content of the stratum corneum is

normally about 30%.

In the stratum corneum there are also protein

fillagrin which can degradate to amino acid36


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EFFECTOFENVIRONMENTTONATURAL

MOISTURIZINGFACTORS(NMF) INTHESKIN

In dry weatherthe skin is dryThe proteolytic

enzyme is activated to breakdown filaggrinprotein to amino acidsamino acid is NMF

which control the osmotic pressure of the skinand the amount of water it holds.

There is less need for breakdown of filaggrin in

humid weather than in dry weather

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DESQUAMATION

Desquamation is another important factor in keepingthe skin smooth.

Desquamation is the enzymatic process of dissolving

the desmosomes, the protein connections betweencorneocytes, and the eventual shedding of these cells.

There is a normal physiological balance in theproduction of corneoctyes and shedding.

The proteolytic enzymes responsible for desquamationfunction in the presence of a well-hydrated stratum

corneum. These enzymes are located intercellularly.

In the absence of water, the cells do not desquamatenormally and the result is thickened, dry, rough, scaly

skin.39

DESQUAMATION

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Intact corneocytes in upper level of

hydrated stratum corneum

Proteolytic enzymes break proteinconnections between corneocytes

Corneocytes desquamate

Skin stays normal without dry scales

EXTERNALFACTORTHATDAMAGESKIN

Environmental low humidity

Exposure of irritating chemical (solvents,detergents, excessive use of water and soap)

Damage skin barrier, interrupting the lipid

bilayers, removing natural moisturizing factors

loss of water from the stratum corneumdesquamation is not normal

skin is dry and rough

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EFFECTOFULTRAVIOLETRADIATIONONTHESKIN

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EFFECTOFULTRAVIOLETRADIATIONONTHESKIN

UV radiation

UV C (290-200 nm)/Germicidal radiation

Strongly absorbed by DNAlethal for viable cell

Potent mutagenMay contribute to the skin cancer

completely Filtered out by the ozone layer.

UV B (315-290 nm)/sunburn spectrum

2-5% of UV radiation, highest when the sun is directly overthe head

UV A (400-315 nm)

95-98% of UV radiation

UV A I (340-400)

UV A II (320-340)

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PHOTOBIOLOGICALRESPONSE

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EFFECTOFULTRAVIOLETRADIATIONON

THESKIN

1. Acute effectshort live and reversible

Tanning response (pigmentation)protective

against subsequent exposures

Erythema

Injury to langerhans cell and keratinocyte

2. Chronic Effect

Photoaging

Skin cancer

3. Other effect: Synthesis of vit D3

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TANNINGRESPONSE/PIGMENTATION

Pigmentation, the synthesis & distribution of

melanin in the epidermis

Melanin:

Produced byMelanocytes

Production determine by genetic factors, exposure to

light, and hormones

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MELANOCYTES

Irregulary shaped cells with many long processes that

extend between the keratinocytes of the stratum basale

and the stratum spinosum

There is approximately 1 melanocytes per 5-6 basal

keratinocytes

Produce melanin which is stored into melanosomes that

are transfered to keratinocytes through the melanocytes

dendrites prosesses

Signals from keratinocytes regulates melanocytes

survival, dendricity and melanogenesis

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MELANIZATION

Involves several steps:

1. Transcription of protein required formelanogenesis

2. Melanosomes biogenesis

3. Sorting melanogenic protein into melanosomesmelanin biosintesis in the melanosomes

4. Transport of melanosomes into the tips ofmelanocytes

5. Transport of melanosomes into the

keratinocytes

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MELANINBIOSINTHESIS

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Eumelanin



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MELANINTRANSFERFROMMELANOCYTETOKERATINOCYTES

1. Melanosomes are produced by the golgiapparatus of the melanocyte

2. Melanosomes move into melanocyte cell

processes

3. Epithelial cells phagocytize the tips of themelanocyte cell processes

4. The melanosomes, which were produced inside

the melanocytes, have been transferred toepithelial cells and are now inside them

Tate P. Principles of Anatomy and Physiology;McGrawHill. 2009

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cutaneous pigmentation does not depend on

the melanocyte number, but rather on:

melanogenic activity within melanocytes

the proportion of mature melanosomes,

and their transfer/distribution within the

keratinocytes

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EFFECTUV RADIATIONONTANNING

Induce immediate tanning and delayed tanning

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PHOTOAGING

Dry, deeple wrinkled, inelastic, irregularities in

pigmentation

UV radiation cause degenerative changes in

elastin and collagenaccumulate over time and

are largely irreversible

The end result: degradation of type I collagenfibrils and disorganization and degeneration of

dermal connective tissue

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SKINCANCER

UVB

Generation of ROS

Damages melanin

Damages DNA: formation of pyrimidine dimers

between adjacent pyrimidines on the same DNA

strand

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RELATIONS OF THE INTEGUMENTARYSYSTEM

WITH OTHER SYSTEM IN THE BODY

MUSCULOSKELETAL SYSTEM Synthesizes vitamin D3, essential for:

Calcium & Phosphorus absorption (bonemaintenance and growth)

Calcium absorption (muscle contraction)

Contraction of skeletal muscles pull against skin offace, producing facial expressions, important incomunication

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NERVOUS SYSTEM

Nerve endings in skin and subcutaneous tissue

provide input to the brain for touch, pressure,

thermal and pain sensations

Control blood flow and sweat gland activity for

thermoregulation

Stimulates contraction of arrector pili muscles to

elevate hair

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ENDOCRINE SYSTEM

Keratinocytes in skin help activate vitamin D tocalcitriol, a hormone that aids absorption of dietarycalcium and phosphorus

Sex hormones

Stimulate sebaceous gland activity

Influence growth, distribution of subcutaneous fat,and apocrine sweat gland activity

Adrenal hormone

Alter dermal blood flow and help mobilize lipidsfrom adipocytes

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CARDIOVASCULAR SYSTEM

Local chemical changes in dermis cause wideningand narrowing of skin blood vessels, which helpadjust blood flow to the skin

Provides oxygen and nutrients; delivers hormonesand cells of immune system

Carries away carbon dioxide, waste products andtoxins

Provides heat to maintain normal skin temperature

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LYMPHATIC SYSTEM &IMMUNITY

Discourage penetration and growth of microbes: Provide mechanical barriers

Langerhans cells in epidermis : recognizing & processingforeign antigens

Macrophages in the dermis : phagocytize microbes thatpenetrate the skin surface

Mast cells trigger inflammation and initiate the immuneresponse

Defending the integument by providingadditional macrophages and mobilizinglymphocytes 59

RESPIRATORY SYSTEM

Hairs in nose filter dust particles from inhaledair

Stimulation of pain nerve endings in skin mayalter breathing rate

Provide oxygen and eliminates carbon dioxide

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DIGESTIVE SYSTEM

Helps activate vitamin D to the hormonecalcitriol, which promotes absorption of dietarycalcium and phosphorus in the small intestine

Provides nutrients for all cells and lipids forstorage by adipocytes

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URINARY SYSTEM

Assists in excretion of water and solutes

Keratinized epidermis limits fluid loss throughskin

Excretes waste products

Maintains normal pH and ion composition of

body fluids

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REPRODUCTIVE SYSTEM

Nerve endings in skin and subcutaneous tissue respondto erotic stimulicontributing to sexual pleasure

Mammary glands (modified sweat glands) produce milk

Suckling of a baby stimulates nerve endings in skinleading to milk ejection

Skin stretches during pregnancy as fetus enlarges

Sex hormones affect hair distribution, adipose tissuedistribution in subcutaneous layer, and mammary glanddevelopment

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REFERENCES

Tortora GJ. Principles of anatomy and physiology. 11thed;

John Wiley: 2006

Tate P. Principles of anatomy and physiology. McGrawHill.

2009

Feingold. The role of epidermal lipids in cutaneous

permeability barrier homeostasis. J. Lipid Res. 2007. 48:25312546.

Denda. Skin barrier function as a self-organizing system.Forma, 2000. 15:227232

Wolff K, Goldsmith L, Katz S, Gilchrest B, Paller A, LeffellD. Fitzpatrics dermatology in general medicine. 7 ed.Mc.GrawHill. 2008

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Handout Fisiologi Kulit