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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 other system

SKIN PHYSIOLOGY
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Dr. Trinovita Andraini, Mbiomed Dr. Imelda Rosalyn Sianipar, MBiomed Department of physiology, FMUI
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THE INTEGUMENTARY SYSTEM

Integumentary System (inte = whole; -gument = body covering ) Two major components:

SKIN (CUTANEOUS MEMBRANE)

Largest organ of the body, both surface area & weight In adults, covers an area of about 2m 2 weighs 4.5 5 kg (16% of total body weight) Has 2 components:

Cutaneous membrane / skin Accessory structure: hair, nails, & multicellular exocrine glands

Epidermis Dermis
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SKIN (CUTANEOUS MEMBRANE)

The

Skin Structure

epidermis is the ectodermally derived outer layer composed of keratinized stratified squamous epithelium.

The

dermis is the mesodermally derived layer of dense irregular collagenous connective tissue that underlies and interdigitates with the epidermis.
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ACCESSORY SKIN STRUCTURES

1. 2.

HAIR AND HAIR FOLLICLE

Hair and hair follicles Smooth muscle arrector pilli 3. Cutaneous glands 4. Nails

- Has minor protective function

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GLANDS OF THE SKIN

GLANDS IN THE SKIN

Skin

Sebaceous

2 types of exocrine glands: glands and sweat glands

Major glands: Exocrine glands

Consist of: 1. Sebaceous glands (oil) 2. Sweat glands
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Sebaceous

(oil) glands oily lipid secretion sebum inhibits bacteria growth, lubricates and protects the keratin of the hair shaft and conditions the surrounding skin. Sebaceous follicles (not associated with hair follicles) discharge sebum directly onto the epidermis: on the face, back, chest, nipples and external genitalia

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GLANDS IN THE SKIN

Sweat

GLANDS IN THE SKIN

Merocrine -

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 puberty nutrient source for bacteria - Controlled by nervous system and circulating hormones

(Eccrine) sweat glands More numerous than apocrine (adult : 25 million) palms, soles and forehead >> - Sweat produced = sensible perspiration - 99% water + electrolites (NaCl), organic nutrients, peptide (AntiBiotik properties), waste products. pH 4.0 -6.8
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GLANDS IN THE SKIN

Functions -

GENERAL FUNCTION OF THE INTEGUMENTARY SYSTEM

Protection Excretion and Absorption Maintenance of Body Temperature

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 of dermicidin
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Sensation

Synthesis of Vitamin 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

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

GENERAL FUNCTION MAINTENANCE OF BODY TEMPERATURE

* Local control * Neural control (primary determining factor)

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GENERAL FUNCTION
E. Synthesis of vitamin D3 - Action of UV rays in sunlight to the molecule in the skin. - The role of liver and kidneys to produce the most active form of vitamin D3

SYNTHESIS OF VITAMIN D3
7 dehydrocholesterol (in the skin)
UV Radiation

Cholecalciferol (Vit. D3)

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Guyton&Hall. 2011

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PROTECTION FUNCTION OF THE SKIN

PROTECTION FUNCTION OF THE SKIN

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

INTERNAL MILIEU OF THE HOST

SKIN

HOSTILE EXTERNAL ENVIRONMENT

The chief function of the skin to form a barrier between the external environment and the internal milieu of the host
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Fitzpatrick Dermatology, 2008

STRATUM CORNEUM
Factors

that play role in the protection function of the skin:

Stratum corneum natural moisturizing factors (NMF) in the skin Oily sebum Pigment melanin protection to UV radiation Acidic pH of perspiration Epidermal langerhans cells and macrofages in the dermis Production of antimocrobial peptides (AMPs) by viable cell in epidermis

Localized in the outer epidermal 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

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The impermeability of water of the skin is 1000 times higher than that of other membranes of living organisms

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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 Keratinization is the transformation process of stratum basale cells into stratum corneum cells The time from cell division to shedding from the stratum corneum: 28 days

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EPIDERMAL LAYER

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Fitzpatrick Dermatology, 2008

KERATINIZATION

KERATINIZATION

At the stratum basale, keratinocytes stem cells devide into daughter cells, which are displaced outward Keratinocytes differentiate through successive overlying layers to enter the stratum corneum During differentiation, keratinocyte on the Stratum spinosum and granulosum generate lamellar bodies containing lipid During the terminal differentiation, lipid matriks from lamellar bodies spread over to the intercellular domains of stratum corneum and form a bilayer stucture Keratinocytes die, apoptosis and their cellular organelles, nuclei and cytoplasm disappear corneocytes The cells appear flatened and the keratin filaments 27 (involucrin) align the corneocytes into disulphide cross linked macrofibres.

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

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EXTRACELLULAR LIPID MATRIX IN

STRATUM CORNEUM

FORMATION OF THE EXTRACELLULAR LIPID

MATRIX ON STRATUM CORNEUM

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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Feingold. The role of epidermal lipids in cutaneous permeability barrier homeostasis. J. Lipid Res. 2007. 48: 2531 2546.

EXTRACELLULAR LIPID MATRIX MEDIATE

PERMEABILITY BARRIER FUNCTION

EXTRACELLULAR LIPID MATRIX MEDIATE

PERMEABILITY BARRIER FUNCTION
Cholesterol: plays an important role in regulating desquamation FFAacidification of the stratum corneum (pH 55,5) important for enzymes activities, eg. Beta glucocerebrosidase and acidic sphyngomyelinase

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 of skin.

Ceramidestrap water molecules in their hydrophilic (water attracting) region Glycerol (from breakdown of phospholipid by PLA2)water holding agentkeep stratum corneum hydratedcrucial for smooth and flexible skin

If ph > Beta glucocerebrosidase activities is reducedthe processing to form ceramide is impaired abnormalities of extracellular lipid membranes decreased permeability barrier function activities of protease increases corneosytes desquamation

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AFFECT OF ENVIRONMENT TO SKIN BARRIER SKIN BARRIER HOMEOSTASIS

REGULATION OF PERMEABILITY
BARRIER REPAIR

Skin barrier function has ability to adapt to the environment sense the environment change and reorganizes its function to adapt the new environment Low humidity, mechanical assault, chemical assault (eg. treatment with an organic solvent or detergent) stratum corneum barrier function demage homeostasis process accelerated:
Lipid synthesis Lipid processing Acceleration of exocitosis of lamellar bodies Barriers recovers to its original level

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 barrier
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REGULATION OF PERMEABILITY
BARRIER REPAIR

EFFECT OF ENVIRONMENT TO NATURAL MOISTURIZING FACTORS (NMF) IN THE SKIN

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 acid

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Feingold. The role of epidermal lipids in cutaneous permeability barrier homeostasis. J. Lipid Res. 2007. 48: 2531 2546.

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EFFECT OF ENVIRONMENT TO NATURAL MOISTURIZING FACTORS (NMF) IN THE SKIN

DESQUAMATION

In dry weather the skin is dry The proteolytic enzyme is activated to breakdown filaggrin protein to amino acids amino acid is NMF which control the osmotic pressure of the skin and the amount of water it holds. There is less need for breakdown of filaggrin in humid weather than in dry weather

Desquamation is another important factor in keeping the skin smooth. Desquamation is the enzymatic process of dissolving the desmosomes, the protein connections between corneocytes, and the eventual shedding of these cells. There is a normal physiological balance in the production of corneoctyes and shedding.

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The proteolytic enzymes responsible for desquamation function in the presence of a well-hydrated stratum corneum. These enzymes are located intercellularly. In the absence of water, the cells do not desquamate normally and the result is thickened, dry, rough, scaly skin.

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DESQUAMATION Intact corneocytes in upper level of hydrated stratum corneum Proteolytic enzymes break protein connections between corneocytes Corneocytes desquamate Skin stays normal without dry scales
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EXTERNAL FACTOR THAT DAMAGE SKIN

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 corneum desquamation is not normal skin is dry and rough

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EFFECT OF ULTRAVIOLET RADIATION

ON THE SKIN

EFFECT OF ULTRAVIOLET RADIATION

ON THE SKIN

UV radiation

UV C (290-200 nm)/Germicidal radiation

Strongly absorbed by DNA lethal 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 over the 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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Fitzpatrick Dermatology, 2008

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EFFECT OF ULTRAVIOLET RADIATION ON PHOTOBIOLOGICAL RESPONSE

THE SKIN

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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Fitzpatrick Dermatology, 2008

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TANNING RESPONSE/PIGMENTATION

MELANOCYTES

Pigmentation, the synthesis & distribution of melanin in the epidermis Melanin:

Produced by Melanocytes Production determine by genetic factors, exposure to light, and hormones

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
1.

MELANIN BIOSINTHESIS

2. 3.

4.

5.

Involves several steps: Transcription of protein required for melanogenesis Melanosomes biogenesis Sorting melanogenic protein into melanosomes melanin biosintesis in the melanosomes Transport of melanosomes into the tips of melanocytes Transport of melanosomes into the keratinocytes
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Eumelanin
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Fitzpatrick Dermatology, 2008

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MELANIN TRANSFER FROM MELANOCYTE TO KERATINOCYTES

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

1.

Melanosomes are produced by the golgi apparatus of the melanocyte

2.

Melanosomes move into melanocyte cell processes

Epithelial cells phagocytize the tips of the melanocyte cell processes The melanosomes, which were produced inside the melanocytes, have been transferred to epithelial cells and are now inside them 50

3.

4.

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

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EFFECT UV RADIATION ON TANNING

PHOTOAGING
Dry, deeple wrinkled, inelastic, irregularities in pigmentation UV radiation cause degenerative changes in elastin and collagen accumulate over time and are largely irreversible The end result: degradation of type I collagen fibrils and disorganization and degeneration of dermal connective tissue

Induce immediate tanning and delayed tanning

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SKIN CANCER

RELATIONS OF THE INTEGUMENTARY SYSTEM WITH OTHER SYSTEM IN THE BODY

MUSCULOSKELETAL SYSTEM

UVB
Generation of ROS Damages melanin Damages DNA: formation of pyrimidine dimers between adjacent pyrimidines on the same DNA strand

Synthesizes vitamin D3, essential for: Calcium & Phosphorus absorption (bone maintenance and growth) Calcium absorption (muscle contraction) Contraction of skeletal muscles pull against skin of face, producing facial expressions, important in comunication

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NERVOUS SYSTEM

ENDOCRINE SYSTEM

Nerve endings in skin and subcutaneous tissue provide input to the brain for touch, pressure, thermal and pain sensations

Keratinocytes in skin help activate vitamin D to calcitriol, a hormone that aids absorption of dietary calcium 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 lipids from adipocytes

Control blood flow and sweat gland activity for thermoregulation Stimulates contraction of arrector pili muscles to elevate hair

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CARDIOVASCULAR SYSTEM

LYMPHATIC SYSTEM & IMMUNITY

Discourage

Local chemical changes in dermis cause widening and narrowing of skin blood vessels, which help adjust blood flow to the skin

penetration and growth of microbes:

Provides oxygen and nutrients; delivers hormones and cells of immune system Carries away carbon dioxide, waste products and toxins Provides heat to maintain normal skin temperature

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Provide mechanical barriers Langerhans cells in epidermis : recognizing & processing foreign antigens Macrophages in the dermis : phagocytize microbes that penetrate the skin surface Mast cells trigger inflammation and initiate the immune response
Defending

the integument by providing additional macrophages and mobilizing lymphocytes

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RESPIRATORY SYSTEM

DIGESTIVE SYSTEM

Hairs

air

in nose filter dust particles from inhaled

Helps activate vitamin D to the hormone calcitriol, which promotes absorption of dietary calcium and phosphorus in the small intestine Provides nutrients for all cells and lipids for storage by adipocytes

Stimulation

of pain nerve endings in skin may alter breathing rate oxygen and eliminates carbon dioxide

Provide

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URINARY SYSTEM
Assists

REPRODUCTIVE SYSTEM

Keratinized

skin

in excretion of water and solutes epidermis limits fluid loss through

Excretes

Maintains

waste products normal pH and ion composition of body fluids

Nerve endings in skin and subcutaneous tissue respond to erotic stimuli contributing to sexual pleasure Mammary glands (modified sweat glands) produce milk Suckling of a baby stimulates nerve endings in skin leading to milk ejection Skin stretches during pregnancy as fetus enlarges

Sex hormones affect hair distribution, adipose tissue distribution in subcutaneous layer, and mammary gland development
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REFERENCES

Tortora GJ. Principles of anatomy and physiology. 11th ed; 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, Leffell D. Fitzpatrics dermatology in general medicine. 7 ed. Mc.GrawHill. 2008
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Thank you

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