皮膚科學基礎概論. Overview of the Skin The skin is one of the largest organs in the body:...

皮膚科學基礎概論皮膚科學基礎概論

Overview of the SkinOverview of the Skin• The skin is one of the largest organs in the body: surface area ≒ 1.8 m2 weight: approximately 16% of our body weight

• Four main functional areas: 1. Epidermis: the major protective layer derived from ectoderm

2. Dermis: the major support layer derived from mesoderm

3. Skin Appendages: derived from both ectoderm and mesoderm Eccrine Sweat Gland

Apocrine Sweat Gland Sebaceous Gland Hair Follicle Nails

Arrector Pili muscle 4. Subcutis: this layer consists of loose connective tissue and fat

SKINSKIN

Functions of the SkinFunctions of the Skin1. barrier to physical agents

2. protects against mechanical injury

3. prevents dehydration of body through fluid loss

4. reduces the penetration of UV Radiation

5. helps regulate body temperature

6. acts as a sensory organ

7. acts as an outpost for immune surveillance

8. plays a role in Vitamin D production

9. has a cosmetic association 

EpidermisEpidermis

Epidermis I.Epidermis I.

• a continually renewing, stratified, squamous epithelium that keratinizes and gives rise to derivative structures (pilosebaceous units, nails & sweat glands) called appendages

• about 0.4 to 1.5 mm in thickness (thickest --- palms & soles)

• full-thickness skin:1.5-4 mm

Epidermis II.Epidermis II.• keratinocytes• Melanocytes• Langerhans cells• Merkel cells *basement membrane: separates epidermi

s & dermis, mediates their attachment

KeratinocyteKeratinocyte• ectodermally derived• > 80 percent of the epidermal cells• cytoplasmic keratin filaments:

1. ＞ 30 different keratins2.a hallmark of the keratinocyte and

other epithelial cells3.structural (cytoskeletal) role

* desmosomes # modified desmosomal junctions

Layers of the epidermisLayers of the epidermis

1.Basal Cell Layer (stratum basale) I1.Basal Cell Layer (stratum basale) I• Mitotically active, columnar-shaped keratinocytes. attach

to the basement membrane zone by hemidesmosomes.

• The normal transit time for a basal cell, from the time it detaches from the basal layer to the time it enters the stratum corneum, is at least 14 days.

• Transit through the stratum corneum and desquamation require another 14 days.

1. Basal Cell Layer (stratum basale) II1. Basal Cell Layer (stratum basale) II• Melanocytes: 5-10% of the layer and make melanin w

hich is transferred to neighboring keratinocytes via dendritic processes– neural crest origin– most numerous on the face and other exposed areas o

f skin• Epidermal melanin unit: Approximately 36 basal an

d suprabasal keratinocytes are thought to coexist functionally with each melanocyte

• Merkel cells: among basal keratinocytes in particular regions of the body (in hairy skin and in the glabrous skin of the digits, lips, regions of the oral cavity, and the outer root sheath of the hair follicle) and join with them by desmosomal junctions – mechanoreceptors

2. Spinous Cell Layer (stratum spinosum)2. Spinous Cell Layer (stratum spinosum) • Suprabasal spinous cells are polyhedral in shape (spine-li

ke appearance of the cell margins)• The “spines” of spinous cells:abundant desmosomes, c

alcium-dependent cell surface modifications that promote adhesion of epidermal cells and resistance to mechanical stresses

• Desmosomes:a mechanical coupling between epidermal cells, gap junctions between keratinocytes are sites of physiologic communication (regulation of cell metabolism, growth, and differentiation)

• Langerhans cells: from bone marrow, mostly found in this layer. dendritic, immunologically active cells that play a role in antigen presentation.

3. Granular Cell Layer (stratum granulosum)3. Granular Cell Layer (stratum granulosum) • Flattened cells and lose their nuclei. In cytoplasm, kerat

ohyalin granules as well as membrane-coating granules which expel their lipid contents into the intercellular spaces.

• The most apparent structures within these cells: basophilic, keratohyalin granules

• Keratohyalin granules are membrane-coating granules which expel their lipid contents into the intercellular spaces.

• At the interface between the granular and cornified cell layers, “barrier” lipids (e.g., sphingolipids) are formed

4. Horny Layer (stratum corneum)4. Horny Layer (stratum corneum) • Complete transition from a granular to a cornified cell is accompanied

by a 45 to 86 percent loss in dry weight• The layers of resultant cornified cells provide mechanical protection to

the skin and a barrier to water loss and permeation of soluble substances from the environment

• The stratum corneum barrier is formed by a two-compartment system of lipid-depleted protein-enriched corneocytes surrounded by a continuous extracellular lipid matrix

• Horny cell: 1. the flattened, polyhedral-shaped, horny cell is the largest cell of the epidermis 2. Its shape and surface features are adapted to maintain the integrity of the stratum corneum yet allow for desquamation 3. the cell contain keratins and filaggrin

• Three key lipid types—cholesterol, ceramides, and free fatty acids—form the lamellar bilayers

Regulation of Epidermal Regulation of Epidermal Proliferation and DifferentiationProliferation and Differentiation

1. Integrins: Keratinocytes express several integrins and important to skin homeostasis

2. Growth Factors: epidermal growth factor (EGF), transforming growth factor (TGF)-α, TGF-ß, keratinocyte growth factor (KGF)...

3. Cytokines: keratinocyte-derived cytokines (interleukin (IL)-1α, IL-6, IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF)

4. Retinoids5. Vitamin D36. Calcium7. Apoptosis

The dermal–epidermal The dermal–epidermal junction (DEJ)junction (DEJ)

• The DEJ is a basement membrane zone that forms the interface between the epidermis and dermis

• Function: 1. attach the epidermis and dermis to each other 2. provide resistance against external shearing forces 3. serves as a support for the epidermis 4. determines the polarity of growth 5. directs the organization of the cytoskeleton in basal cells 6. provides developmental signals 7. serves as a semipenetrable barrier

Three supramolecular networkThree supramolecular networks of DEJs of DEJ

1. Hemidesmosome-anchoring filament complex

2. Basement membrane

3. Anchoring fibrils

Overview of the DermisOverview of the Dermis• a supportive connective

tissue matrix containing numerous specialized structures.

• The dermal thickness varies being thinnest (0.6 mm) on the eyelids and thickest (3 mm or more) on the back, palms, and soles.

Contains of the dermis IContains of the dermis I1. Collagen fibers• Make up 70% of the dermis and give structural toughness a

nd strength.• Type I, III, and V account for the greatest proportion of the c

ollagen in adult dermis

2. Elastic fibers • Account for 4% of the dermal matrix protein• loosely arranged in all directions and give elasticity to the s

kin• Elastic fibers are also present in the walls of cutaneous blo

od vessels and lymphatics and in the sheaths of hair follicles

Contains of the dermis IIContains of the dermis II3. Ground substance• consists of a semi-solid matrix of Proteoglycans ( hyal

uronic acid, chondroitin sulfate, heparan sulfate…)

4. Cells • Fibroblasts• Macrophages• Mast cells

Organization of the DermisOrganization of the Dermis1. Papillary Dermis• Beneath the epidermis ex

tending to vascular boundary of subpapillary plexus

2. Rticular Dermis• The dominant region of th

e dermis• Composed of large-diame

ter collagen fibers and mature elastic fibers

Cutaneous vasculature ICutaneous vasculature IFunction: • provide nutrition• regulation of temperature• blood pressure• wound repair• immunologic events

Cutaneous vasculature IICutaneous vasculature II1. Arteries• Musculocutaneous arteries in the subcutaneous fat mi

grate upwards to give rise to a subpapillary plexus at the papillary/reticular dermal boundary.

• Subpapillary plexus gives off branches of its own that branch upwards to the dermal papillae.

• Each dermal papillae has a single loop of capillary vessels, one arterial and one venous.

Cutaneous vasculature IIICutaneous vasculature III2. Veins• Veins drain from the venous side of the l

oop and branch downward to form the venous return network of the mid-dermis and subcutaneous layer.

Cutaneous vasculature IVCutaneous vasculature IV3. Lymphatic Vessels• Function: regulating pressure of the inte

rstitial fluid, clearing the tissue of cells, proteins, lipids, bacteria, and degraded substances

• The lymphatics originate in the papillae then drain into increasingly larger vessels that ultimately reach the regional lymph nodes.

Nerves and Receptors I Nerves and Receptors I

• The nerve networks of the skin – somatic sensory – sympathetic autonomic fibers

• Nerve fibers of the skin– myelinated or non-myelinated– contain neuropeptides such as

substance P.

Nerves and Receptors IINerves and Receptors II1. Sensory fibers• The sensory fibers are receptors of touch, pain, temperature,

itch, and mechanical stimuli

• Rceptors are particularly dense in hairless areas such as the palms, face areola, labia, and glanspenis

• Free sensory nerve endings can be seen in both the dermis and the epidermis ； In the epidermis, they may end on Merkel cells which detect pain, itch and temperature.

• In the dermis, there are specialized corpuscular receptors such as: – Pacinian corpuscle: detects pressure and vibration– Meissner's corpuscle: touch sensitive and mainly located i

n the dermal papillae of the hands and feet.

Nerves and Receptors IIINerves and Receptors III2. Motor fibers• Sympathetic motor fibers are codistri

buted with the sensory nerves in the dermis until they branch to innervate the sweat glands, vascular smooth muscle, the arrector pili muscle of hair follicles, and sebaceous glands

Nerves and ReceptorsNerves and Receptors

Appendages of the SkinAppendages of the Skin

Hair FollicleHair Follicle• Functions 1. prevent heat loss 2. as a “first line of defense” 3. as a “touch organ” 4. a conduit in the delivery of scents secreted by the sebaceous and apocrine glands 5. an important component of the body image• Hair follicles are distributed throughout t

he integument with the exception of the palms, soles, and portion of the genitalia (so-called glabrous skin)

• The highest density of follicles is on the scalp (about 100000 hair follicles), growth rate is about 1 cm/month

Compartments of hair shaft and hair follicleCompartments of hair shaft and hair follicle

The Hair Cycle The Hair Cycle 1. Anagen: 2-6 years, 85-90%2. Catagen: 2-3 weeks, less than 1%3. Telogen: 2-3 months, about 13%• Each follicle goes through the hair cycle 10 to 20 times in a lifetime

Sebaceous glandsSebaceous glands• The sebaceous glands go hand in hand wit

h hair follicles. • They are especially prominent with the hai

r follicles of the face, scalp, chest, and back ； they are absent on non-hairy glabrous skin.

• Sebaceous glands, being holocrine glands, form their secretion by decomposition of their cells.

• As a child, these glands are small, but they enlarge and become active during puberty due to their androgen sensitivity.

Sweat Glands ISweat Glands I• Sweat glands reside in the dermis and produce a watery se

cretion. • There are two types of sweat glands: eccrine and apocrine.

1. Eccrine Sweat Glands • Anatomy: Coiled secretory portion is located in the reticula

r dermis. Excretory ducts spirals upwards and opens onto the skin surface.

• Distribution: all over our body, most dense on our axillae, palms, soles, and forehead.

• Nervous control: The eccrine glands are under sympathetic cholinergic control.

• Composition: Inorganic ions (NaCl, K, HCO3-), Lactate, Urea,

Ammonia and Amino acids, Proteins and proteases, PH between 4-6.8

Sweat Glands IISweat Glands II2. Apocrine • Anatomy: apocrine sweat glands open into hair follicles

and are larger glands. • Distribution: They densely populate the axillae, perineu

m, and areolae. They are not functional until just before puberty.

• Nervous control: The apocrine sweat glands are innervated by sympathetic adrenergic nerve fibers.

• Composition: The sweat is generated by "decapitation" secretion of the gland's cells.

• The apocrine sweat is milky and viscid without order when it is first secreted. It is only after skin's bacteria has acted upon the apocrine sweat that it develops an odor.

Eccrine ApocrineEccrine Apocrine

NailsNails

• A plate of hardened and densely packed keratin. • Nail matrix is full of dividing cells which age, keratinize and progress forward to form the nail plate.

NailsNails• Nail plate is what we consider our "nail" and h

as a thickness of 0.3-0.5 mm and grows an average of 0.1 mm/day. (fingernails do grow faster than toenails)

• Nail bed is just below the nail plate. • Hyponychium is the thickened epidermis whic

h is below the free edge of the nail. • The pink color of the nail can be accounted for

by dermal capillaries that are adjacent to the nail bed.

• The distal white lunula is basically the visible part of the nail matrix.

Primary skin lesionsPrimary skin lesions

MaculesMacules• A macule is a circumscribed, fl

at lesion that differs fromsurrounding skin because of its color.

• They may be the result of hyperpigmentation, hypopigmentation, vascularabnormalities, capillary dilatation (erythema), or purpura (extravasated redblood cells).

Papule Papule • A papule is a small, solid, elevated lesion.• Papules are generally smaller than 0.5 cm in diameter.

PlaquePlaque• A plaque is a mesalike elevation that occupies a r

elatively large surface area in comparison with its height above skin level

PatchPatch

• A patch is a portion of any surface markedly different in appearance or character from what is around it.• Dermatologists have used this

term in different ways: some restrict its use to the description of very large macules; others use it to refer to relatively thin but large plaques.

NoduleNodule• A nodule is a palpable, solid, round or ellipsoidal lesion. • Depth of involvement rather than diameter, differentiate a nodule from a papule.

Wheals Wheals • A wheal is a rounded or flat-topped papule or plaque

that is characteristically evanescent, disappearing within hours.

• The epidermis is not affected: there is no scaling.

Vesicles and BullaeVesicles and Bullae• A vesicle is a circumscribed, elevated lesion that contains fluid.• A bullae is a vesicle larger than 0.5 cm

PustulePustule• A pustule is a circumscribed, r

aised lesion that contains a purulent exudate.

• Pus, composed of leukocytes with or without cellular debris,

may contain bacteria or may be sterile,

Erosion and UlcerErosion and Ulcer• An erosion is a moist, circumscribed, usually depressed lesion that results from loss of all or a portion of the viable epidermis.• An ulcer is a “hole in the skin” in which there has been destruction of the epidermis and at least the upper dermis.

Clinical signsClinical signs

Dimple signDimple sign• Useful maneuver in differentiating dermatofibro

ma from melanoma.• Application of lateral pressure with the thumb a

nd index finger results in the formation of depression (dimple) in a dermatofibroma.

Nikolsky’s signNikolsky’s sign• It refers to the sheetlike removal of epidermis by ge

ntle traction.• Pemphigus vulgaris, Toxic epidermal necrolysis

Darier’s signDarier’s sign• It refers to the development of an urticar

ial wheal in the lesions of urticaria pigmentosa afer they are rubbed.

Auspitz’s signAuspitz’s sign• It refers to the appearance of

pinpoint dots of blood at the tops of ruptured capillaries when scale is forcibly removed from psoriatic plaques.

ExaminationsExaminations

1. KOH Smear1. KOH Smear

• KOH digest the proteins, lipids, and most of the other epithelial debris present in the samples.

• Diagnosis: 1. Fungual infection (dermatophyte, candidiasis, tinea versicolor…) 2. Scabies 3. Pediculosis…

2. Wood’s light examination2. Wood’s light examination• 原理 : Longwave ultraviolet light (320-400nm) 照射病灶產生 fluorescence• Diagnosis: 1. Fungual infection (ex. Tinea capitis, Tinea versicolor) 2. Bacteria infection (ex. Erythrasma) 3. Porphyria 4. Pigmentation (ex. Vitiligo and melasma)

Wood’s light: resultsWood’s light: results• Microsporum : bright blue• Malassezia furfur : golden green• Corynebacterium minutissimun: coral red• Pseudomonas : yellowish green• Porphyria : pinkish-red• Localize site of melanin ( 加深位於表皮層的

黑色素 , 但真皮層黑色素反而變不明顯 ) freckle and melasma darker Mongolian sacral spot lightening

3. Tzanck Smear3. Tzanck Smear• Diagnosis: 1. Herpes virus infection: Chickenpox, Herpes simplex, Herpes zoster 2. Bullous disease: Pemphigus, Pemphigoid• Procedure: 1. 以刀片輕刮水泡 base , 在均勻塗抹於載玻片上 2. Liu’s stain• Results: 1. Herpes virus infection: Multinucleated giant cells 2. Bullous disease: 表淺的 kerationcyte 較為扁平， 較深的 keratinocyte 較立方形，故可由水泡底部表 皮細胞的形狀來判斷水泡位置之深淺

Multinucleated giant cellsMultinucleated giant cells

4. Patch test4. Patch test• 原理 : To elicit an immune response by challenging already sensitized persons to define allergens & assessing the degree of response• Diagnosis: allergic contact dermatitis• Procedure: 將 allergens 置於圓形凹槽中，再貼於上背部， 於 48hr 後判讀• Results: +? (Doubtful reaction): faint erythema only + (Weak positive reaction): erythema, infiltration, possibly papules ++ (Strong positive reaction): erythema, infiltration, papules, vesicles +++ (Extreme positive reaction): intense erythema and infiltration and coalescing vesicles

5. Biopsy of the skin5. Biopsy of the skin• Indication: Biopsy is indicated in all suspected neoplas

m and all dermatologic disorder in which diagnosis is not possible by clinical exam alone

• Type: Scalpel biopsy ( incisional ; excisional ), Punch biopsy, Shave biopsy, Curratage

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