General General dermatologydermatology

As.MUDr. Spyridon Gkalpakiotis, As.MUDr. Spyridon Gkalpakiotis, PhDPhD

Dermatovenereology deparment of Dermatovenereology deparment of Third Faculty of Medicine, Charles Third Faculty of Medicine, Charles

University,PragueUniversity,Prague

Skin is the interface between Skin is the interface between humans and their environmenthumans and their environment

The largest organ in the bodyThe largest organ in the body It weighs an average of 10% of body It weighs an average of 10% of body

weight and covers an area of 2 mweight and covers an area of 2 m22

Many different functions Many different functions

Skin surface with fine wrinkles Skin surface with fine wrinkles divided into polygonal spacesdivided into polygonal spaces

On the soles and palms we find On the soles and palms we find parallel leaves and on the proximal parallel leaves and on the proximal space of fingers they form unique space of fingers they form unique drawings called dermatoglyphs – drawings called dermatoglyphs – used for persons identificationused for persons identification

Configuration depends on the Configuration depends on the disposition of dermal papillaedisposition of dermal papillae

Anatomy of the skinAnatomy of the skin

EpidermisEpidermis DermisDermis HypodermisHypodermis

EpidermisEpidermis

Epidermis is formed from many Epidermis is formed from many layers of closely packed cells called layers of closely packed cells called keratinocyteskeratinocytes

Contains no blood vesselsContains no blood vessels Varies in thickness from less than Varies in thickness from less than

0.1 mm on the eyelids to almost 1 0.1 mm on the eyelids to almost 1 mm on the palms and solesmm on the palms and soles

EpidermisEpidermis

Different layers:Different layers:- Basal layerBasal layer- Spinous or prickle layerSpinous or prickle layer- Granular layerGranular layer- Horny layerHorny layer

Basal layer (stratum Basal layer (stratum basale)basale)

Basal layer is the deepest layer.Basal layer is the deepest layer. Rests on basement membrane to Rests on basement membrane to

which is connected by which is connected by hemidesmosomes hemidesmosomes

Division of cells Division of cells Basal cells have nucleusBasal cells have nucleus Cells are connected each to other by Cells are connected each to other by

desmosomesdesmosomes

Spinous layer (stratum Spinous layer (stratum spinosum)spinosum)

Spinous layer is composed of many Spinous layer is composed of many layers of keratinocytes.layers of keratinocytes.

Differentiating cells, synthesize Differentiating cells, synthesize keratines, bigger than basal cells. keratines, bigger than basal cells.

Kept together by desmosomes and by Kept together by desmosomes and by intercellular cement of glycoproteins intercellular cement of glycoproteins and lipoproteins.and lipoproteins.

Desmosomes contains desmoplakins, Desmosomes contains desmoplakins, desmogleins and desmocollinsdesmogleins and desmocollins

Autoantibodies against proteins of Autoantibodies against proteins of desmosomes like in pemfigus desmosomes like in pemfigus vulgaris, cause detachment of vulgaris, cause detachment of keratinocytes form one another and keratinocytes form one another and so for an intraepidermal blister so for an intraepidermal blister formation.formation.

Granular layer (stratum Granular layer (stratum granulosum)granulosum)

Two or three layers of cells that are Two or three layers of cells that are flatter than those in spinous layerflatter than those in spinous layer

Contains large irregular basophilic Contains large irregular basophilic granules of keratohyalin.granules of keratohyalin.

Granules contatin profilaggrin which Granules contatin profilaggrin which is cleaved to fillagrin as the granular is cleaved to fillagrin as the granular cells move into horny layercells move into horny layer

Horny layer (stratum Horny layer (stratum corneum)corneum)

Flattened dead cells called Flattened dead cells called corneocytescorneocytes

Horny cells normaly have no nuclei Horny cells normaly have no nuclei or intracytoplasmic organelles.or intracytoplasmic organelles.

Lower compact part of the layer is Lower compact part of the layer is called called stratum conjuctumstratum conjuctum, periferal , periferal part which is contiually part which is contiually desquamating is called desquamating is called stradum stradum disjunctumdisjunctum..

Cells in epidermisCells in epidermis

KeratinocytesKeratinocytes

MelanocytesMelanocytes

Langerhans cellsLangerhans cells

Merkel cellsMerkel cells

KeratinocytesKeratinocytes

Main cells of epidermisMain cells of epidermis Produce keratinProduce keratin Differentiation from keratinocytes of basal Differentiation from keratinocytes of basal

cells to corneocytes takes 28 days on the cells to corneocytes takes 28 days on the body and 14 days on the scalpbody and 14 days on the scalp

The primary function of keratinocytes is The primary function of keratinocytes is the formation of a barrier against the formation of a barrier against environmental damage such as pathogens environmental damage such as pathogens (bacteria, fungi, parasites, viruses), heat, (bacteria, fungi, parasites, viruses), heat, UV radiation and water lossUV radiation and water loss

MelanocytesMelanocytes Synthesize melaninSynthesize melanin Ectodermic originEctodermic origin Found mostly in the basal layerFound mostly in the basal layer No dermosomesNo dermosomes Except from epidemis, also in hair bulbs, Except from epidemis, also in hair bulbs,

retina and pia arachnoidretina and pia arachnoid Each dendritic melanocyte associates with a Each dendritic melanocyte associates with a

number of keratinocyte forming „epidermal number of keratinocyte forming „epidermal melanin unit“melanin unit“

Their cytoplasm contains melanosomesTheir cytoplasm contains melanosomes

Langerhans cellsLangerhans cells

Dendritic cells like melanocyteDendritic cells like melanocyte SuprabasalSuprabasal No desmosomesNo desmosomes Key role in many immune reactionsKey role in many immune reactions Antigen presenting cellsAntigen presenting cells UV radiation and local UV radiation and local

corticosteroids reduce their number corticosteroids reduce their number and supress functionand supress function

Merkel cellsMerkel cells

Act as transducers for fine touchAct as transducers for fine touch Non-dendritic cells, lying in or near Non-dendritic cells, lying in or near

basal layerbasal layer Same size as keratinocytesSame size as keratinocytes Concentrated in localised Concentrated in localised

thickenings of epidermis near hair thickenings of epidermis near hair folliclesfollicles

Have desmosomesHave desmosomes

DermisDermis

Layer between epidermis and subcutaneous Layer between epidermis and subcutaneous fatfat

Thickness varies, being gratest in the palms Thickness varies, being gratest in the palms and soles and least in eyelides and penisand soles and least in eyelides and penis

By age it gets thin and loose elasticityBy age it gets thin and loose elasticity Papillary dermisPapillary dermis Reticular dermisReticular dermis Compoused by cells, fibers and amorphouss Compoused by cells, fibers and amorphouss

ground substanceground substance

DermisDermis

The main cells of dermis are The main cells of dermis are fibroblastsfibroblasts

Mononuclear phagocytesMononuclear phagocytes LymphocytesLymphocytes Langerhans cellsLangerhans cells Mast cellsMast cells

DermisDermis

Fibers: collagen and elastic fibersFibers: collagen and elastic fibers Ground substance of the dermis consists Ground substance of the dermis consists

largerly of 2 glycosaminoglycans largerly of 2 glycosaminoglycans ( hyaluronic acid and dermat sulphate). ( hyaluronic acid and dermat sulphate).

It binds water, allowing nutrients, hormones It binds water, allowing nutrients, hormones and wast products to pass through epidermisand wast products to pass through epidermis

It acts as a lubricant between collagen and It acts as a lubricant between collagen and elastic fiberselastic fibers

It provides bulk, allowing the dermtis to act as It provides bulk, allowing the dermtis to act as a shock absorbera shock absorber

MusclesMuscles

Smooth and striated Smooth and striated Smooth arrector pili muscles Smooth arrector pili muscles Smooth muscle is responsible for Smooth muscle is responsible for

nipple erection and the raising of the nipple erection and the raising of the scrotum by the dartos musclescrotum by the dartos muscle

VesselsVessels

Blood supply regulates temperatureBlood supply regulates temperature Two horizontal layersTwo horizontal layers Deep plexus just above Deep plexus just above

subcutaneous fat, supply sweat subcutaneous fat, supply sweat glands and hair papillaeglands and hair papillae

Superficial plexus is in papillary Superficial plexus is in papillary dermisdermis

NervesNerves

One milion nerve fibersOne milion nerve fibers Most are found in the face and extremitiesMost are found in the face and extremities Their cell bodies lie in the dorsal root Their cell bodies lie in the dorsal root

gangliaganglia Both myelinated and non-myelinatedBoth myelinated and non-myelinated Most free sensory nerves end in the dermisMost free sensory nerves end in the dermis Autonomic nerves supply the blood vessels, Autonomic nerves supply the blood vessels,

sweat glands and arrector pili musclessweat glands and arrector pili muscles

NervesNerves

Special receptorsSpecial receptors Vater pacini corpuscle: pressure Vater pacini corpuscle: pressure

(palms and soles, around nipples, (palms and soles, around nipples, anogenital area)anogenital area)

Wagner-Meissner corpuscle: touchWagner-Meissner corpuscle: touch Kraus corpuscle: coldKraus corpuscle: cold Ruffini corpuscle: heatRuffini corpuscle: heat Golgi-Mazoni corpuscle: pressureGolgi-Mazoni corpuscle: pressure

Skin adnexasSkin adnexas

Sebaceous glandsSebaceous glands Sweat apocrine glandsSweat apocrine glands Sweat ecrine glandsSweat ecrine glands HairsHairs NailsNails

Sebaceous glandsSebaceous glands

Face, upper part of chest and back. Face, upper part of chest and back. Not on palms and solesNot on palms and soles

Bind to hair follicle ( pilocebaceous Bind to hair follicle ( pilocebaceous unit)unit)

Function is regulated by hormonesFunction is regulated by hormones Production of sebum composed of Production of sebum composed of   

lipids, wax, and the debris of dead , wax, and the debris of dead fat-producing cellsfat-producing cells

Apocrine sweat glandsApocrine sweat glands

Big sweat glandsBig sweat glands CComposed of a coiled secretory portion located omposed of a coiled secretory portion located

at the junction of the dermis and subcutaneous at the junction of the dermis and subcutaneous fat, from which a straight portion inserts and fat, from which a straight portion inserts and secretes into the infundibular portion of the secretes into the infundibular portion of the hair folliclehair follicle

AAxillae (armpits), the areola of the nipples, and xillae (armpits), the areola of the nipples, and the genitoanal regionthe genitoanal region

Become active during pubertyBecome active during puberty Excrete viscous material rich in lipids (Excrete viscous material rich in lipids (byby

action ofaction of bacteria bacteria, , causcause e a noticeable odoa noticeable odour)ur)

Ecrine sweat glandsEcrine sweat glands

Small sweat glandsSmall sweat glands 3 million merocrine glands3 million merocrine glands   Palms and soles have the highest Palms and soles have the highest

numbersnumbers We dont find them at nail bed, glans We dont find them at nail bed, glans

penis, labia minora, klitoris, red part of penis, labia minora, klitoris, red part of lipslips

Thermoregulation, excretion, protectionThermoregulation, excretion, protection Water, Na, ClWater, Na, Cl

HairsHairs

5 milion hairs ( on head 100 000)5 milion hairs ( on head 100 000) Musculus arrector pili except beard, axila, Musculus arrector pili except beard, axila,

pubicpubic Hair on the head grows 0,35 mm per dayHair on the head grows 0,35 mm per day Three phases: anagen, catagen, telogenThree phases: anagen, catagen, telogen 85% anagen, 1 % catagen, 15% telogen85% anagen, 1 % catagen, 15% telogen Lanugo hair, vellus hair, terminal hairLanugo hair, vellus hair, terminal hair

NailsNails

A A nailnail is a horn-like envelope  is a horn-like envelope covering the dorsal aspect of thecovering the dorsal aspect of the terminal phalanges of fingers and terminal phalanges of fingers and toestoes

Made by keratinMade by keratin They grow 0.12mm per day ( whole They grow 0.12mm per day ( whole

nail takes up to 3-4 months) nail takes up to 3-4 months)

Subcutaneous tissueSubcutaneous tissue

Deepest layer of skinDeepest layer of skin Origin is from mesodermOrigin is from mesoderm Mainly fat tissue formed by Mainly fat tissue formed by

adipocytesadipocytes Eyebrows thin layer 0,6mm, Eyebrows thin layer 0,6mm,

buttocks thick layer ( panniculus buttocks thick layer ( panniculus adiposus)adiposus)

Physiology of skinPhysiology of skin

Barrier ( protection) functionBarrier ( protection) function Secretory functionSecretory function Metabolic functionMetabolic function Reguralatory functionReguralatory function Sensoric functionSensoric function Immunologic functionImmunologic function Deposit functionDeposit function Psychosocial functionPsychosocial function

Barrier fuctionBarrier fuction

Physical barrierPhysical barrier- Mechanical (stratum corneum, Mechanical (stratum corneum,

desmosomes, dermoepidermal desmosomes, dermoepidermal juction)juction)

- Photoprotection (stratum corneum, Photoprotection (stratum corneum, keratohyalin structures, melanin, b-keratohyalin structures, melanin, b-karoten)karoten)

- Protection against heat and cold and Protection against heat and cold and water regulationwater regulation

Barrier fuctionBarrier fuction

Chemical barrier:Chemical barrier:- Acidic resistance of keratinAcidic resistance of keratin- Slight acidic skin layer ( pH 5-6)Slight acidic skin layer ( pH 5-6)- Selfcleaning of skinSelfcleaning of skin- Chemical which invade to skin Chemical which invade to skin

cought by Langerhans cellscought by Langerhans cells

Barrier fuctionBarrier fuction

Biologic barrierBiologic barrier

- Stratum corneum is a barrier for - Stratum corneum is a barrier for bakteriabakteria

- Acidic resistance of keratinAcidic resistance of keratin- Slight acidic skin layer ( pH 5-6)Slight acidic skin layer ( pH 5-6)- Selfcleaning of skin (continuous Selfcleaning of skin (continuous

desquamation)desquamation)- Skin microfloraSkin microflora

Secretory functionSecretory function

KeratinKeratin MelaninMelanin SweatSweat SebumSebum

Secretory functionSecretory function

KeratinKeratin- Firmest structure in our bodyFirmest structure in our body- Formed by keratohyalines granulesFormed by keratohyalines granules- Epidermopoesis needs 20% protein Epidermopoesis needs 20% protein

of daily incomeof daily income- Cells from basal layer to stratum Cells from basal layer to stratum

corneum takes up to 28 days ( in corneum takes up to 28 days ( in psoriasis 4 days ! )psoriasis 4 days ! )

Secretory functionSecretory function

MelaninMelanin- Pigment belonging to polychinones Pigment belonging to polychinones

with high content of tyrosinwith high content of tyrosin- PhotoprotectionPhotoprotection- Stimulated by UV lightStimulated by UV light- Regulated by MSH ( melanocyte Regulated by MSH ( melanocyte

stimulating hormon)stimulating hormon)

Secretory functionSecretory function

SweatSweat- Hypotonic with Na,K,Cl,Ca, phosphate Hypotonic with Na,K,Cl,Ca, phosphate

….but NO proteins, lipids and enzymes….but NO proteins, lipids and enzymes- Ecrine and apocrine glandsEcrine and apocrine glands- Thermoregulation, hydration, excretion Thermoregulation, hydration, excretion

of toxic substancesof toxic substances- Secretion is regulated by body Secretion is regulated by body

temperature and centers in temperature and centers in hypothalamushypothalamus

Secretory functionSecretory function

SebumSebum- Consists of fatty acids, mono – di – Consists of fatty acids, mono – di –

triacylglycerols, parafinstriacylglycerols, parafins- Sebaceous glandsSebaceous glands- Barrier lipid filmBarrier lipid film- Regulated by hormones, diet, stress, Regulated by hormones, diet, stress,

maybe drugs?maybe drugs?

Metabolic functionsMetabolic functions

Skin metabolism is 1/3 of liver Skin metabolism is 1/3 of liver metabolismmetabolism

Metabolism of saccharides, lipis, Metabolism of saccharides, lipis, proteinsproteins

Formation of vitamin D by UV lightFormation of vitamin D by UV light

Deposit functionDeposit function

Water reservoarWater reservoar During defect of skin barrier loss of During defect of skin barrier loss of

water like in atopic dermatitiswater like in atopic dermatitis

ImmunologyImmunology

Skin immune systém (SIS)Skin immune systém (SIS)- KeratinocytesKeratinocytes- Langerhans cellsLangerhans cells- T lymphocytesT lymphocytes- Mast cellsMast cells

T-lymphocytesT-lymphocytes

T-helper:T-helper:- Th1 produce: IL-2, INF-Th1 produce: IL-2, INF-γγ, TNF-a, TNF-a- Th2 produce: IL-4. Il-5, IL-10Th2 produce: IL-4. Il-5, IL-10- Th17 produce: IL-17Th17 produce: IL-17- T-cytotoxic (TC) cellsT-cytotoxic (TC) cells

Hypersensitivity Hypersensitivity reactions reactions

Hypersensitivity is the term given to an Hypersensitivity is the term given to an exaggerated or inappropriate immune exaggerated or inappropriate immune reaction. Ireaction. I

4 types according to Coombs and Gell:4 types according to Coombs and Gell:- Type I: Immediate – anaphylactic typeType I: Immediate – anaphylactic type- Type II: Cytotoxic reactionType II: Cytotoxic reaction- Type III: Immune complex-mediatedType III: Immune complex-mediated- Type IV: Cell mediated (delayed) typeType IV: Cell mediated (delayed) type

Type I: Immediate – Type I: Immediate – anaphylactic typeanaphylactic type

Vasodilatation and outpouring of Vasodilatation and outpouring of fluid from blood vesselsfluid from blood vessels

Drugs, toxins Drugs, toxins IgE mediatedIgE mediated Urticaria and agioedemeUrticaria and agioedeme Anaphylactic shockAnaphylactic shock

Type II: Cytotoxic Type II: Cytotoxic reactionreaction

IgG and IgM antibodiesIgG and IgM antibodies Complement activationComplement activation Takes about 6 hoursTakes about 6 hours Typical of defence against infectious agents such as Typical of defence against infectious agents such as

bacteriabacteria Hemolytic anemia, posttransufion reaction if Hemolytic anemia, posttransufion reaction if

incompatibility of blood typesincompatibility of blood types Drug purpuraDrug purpura Autoimmune diseases (pemphigus, Autoimmune diseases (pemphigus,

pemphigoid )pemphigoid )

Type III: Immune Type III: Immune complex-mediatedcomplex-mediated

Antigen-antibody complexAntigen-antibody complex Complement activationComplement activation OedemaOedema Extravasation of red blood cellsExtravasation of red blood cells Vasculitis, SLE, erythema nodosum, Vasculitis, SLE, erythema nodosum,

erythema exsudativum multiformerythema exsudativum multiform Localised form : „Arthus reaction“Localised form : „Arthus reaction“

Type IV: Cell mediated Type IV: Cell mediated (delayed) type(delayed) type

Mediated by lymphocytesMediated by lymphocytes Delayed hypersensitivity reactions Delayed hypersensitivity reactions

( Mantoux )( Mantoux ) Allergic contact dermatitisAllergic contact dermatitis Induction (sensitisation) and Induction (sensitisation) and

elicitaion (challenge) phaseelicitaion (challenge) phase