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Structure and Function of Skin. Erik Austin, D.O., M.P.H. Epidermis ~ continually renewing stratified squamous epithelium that keratinizes and gives rise to cutaneous appendages Epidermis is 0.4mm thick (eyelid) to 1.5mm thick (palm/sole). Epidermal Cell Types. Keratinocytes ~

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structure and function of skin

Structure and Function of Skin

Erik Austin, D.O., M.P.H.

slide3
Epidermis ~ continually renewing stratified squamous epithelium that keratinizes and gives rise to cutaneous appendages
  • Epidermis is 0.4mm thick (eyelid) to 1.5mm thick (palm/sole)
epidermal cell types
Epidermal Cell Types
  • Keratinocytes ~
  • 80% of cells in epidermis
  • Provide physical protection and immunologic defense
  • Ectodermal origin
  • Mitotically active
  • 4 layers: basalis, spinosum, granulosum, and corneum
slide5
Keratins ~
  • Filament proteins expressed by keratinocytes
  • Classified as:
  • Type I = acidic (K9-20, 40-56.5kD, chromosome 17)
  • Type II = basic/neutral (K1-8, 52-67kD, chromosome 12)
  • Specific keratin pairs are synthesized in distinct epidermal cell layers ~ K5/K14: basal, K1/K10: spinous/granular
  • K6/K16: expressed in hyperproliferative states
slide6
K1/K10 mutation = epidermolytic hyperkeratosis
  • K5/K14 mutation = epidermolysis bullosa
epidermal anatomy
Epidermal Anatomy
  • Basal ~ anchor epidermis and dermis; divides and renews outer layers of skin
  • Epidermal germinative cells divide q 19 days
  • Total epidermal renewal time = 45 days
  • Basal cells are columnar and attach to the BM via hemidesmosomes
  • BASAL LAYER ~ EXPRESS K5/K14
slide9
Hemidesmosomes are protein and are composed of the following:
  • BPAG1 (230kd), BPAG2 (180kd), plectin, and integrin a6B4
  • STEM CELLS (regenerating cells) are located in basal layer (in the HAIR BULGE)
slide10
Spinosum ~
  • Spines = bridges = desmosomes
  • SPINOSUM LAYER ~ EXPRESS K1/K10
  • Lamellar granules = lysosomes
  • Hyperproliferative states lead to increased K6/K16 production, with decreased K1/K10
  • Desmosomes: desmoplakin 1 & 2, envoplakin and periplakin
  • Desmosome components: desmoglein 1 & 3, plakoglobin, plakophilin, desmocollin I & II, keratocalmin
slide11
Keratocalmin is a calmodulin binding protein
  • Desmosomal components are the targets of autoantibodies and bacterial toxins
  • Gap Junctions/Connexins provide pores
slide12
Granulosum ~
  • Contain keratohyaline and trichohyaline granules
  • Keratohyaline granules are composed of profilaggrin, keratins, and loricrin
  • Profilaggrin forms fillagrin = filament aggregation protein
  • Lamellar bodies (Odland bodies): discharge lipid components and provide cohesion
slide13
Cornified envelope ~ involucrin, loricrin, keratolinin, cornifin and envoplakin ~ encoded on chromosome 1q21
  • Cells loose cytoplasm and release calcium which activates transglutaminase which catalyzes cross-linking of the cornified envelope (note: transglutaminase 1 is mutated in lamellar ichthyosis)
  • Keratin filaments are 63-67kd
slide14
Corneum ~
  • Cells contain keratin and filaggrin
  • Lamellar granules produce ceramides, fatty acids, and cholesterol
  • Parakeratosis = incompletely keratinized cells with retained nuclei
slide15
Growth factors regulate epidermal growth:
  • Transforming Growth Factor alpha: made by keratinocytes in epidermis
  • Keratinocyte Growth Factor: made in dermis
  • TGF-B: made by keratinocytes; promotes differentiation
  • Platelet Derived Growth Factor: made in epidermis; acts on melanocytes
  • Basic Fibroblast Growth Factor: made in epidermis; induces melanocyte growth
  • Tumor Necrosis Factor alpha: cytokine involved with inflammation
other epidermal cells
Other Epidermal Cells
  • Melanocytes ~
  • Dendritic pigment synthesizing cells derived from neural crest and are found in basal layer
  • Life cycle depends on tyrosine kinase receptor c-kit and its stem cell
  • Melanocytes contain melanosomes which produce melanin
  • Melanocytes stain for DOPA and silver stains
  • Markers: S100, Vimentin, HMB-45, MART 1
slide18
Epidermal melanin unit: one melanocyte + many keratinocytes
  • Skin color is determined by the NUMBER, SIZE, AND DISTRIBUTION OF MELANOSOMES, MELANOSOMES, MELANOSOMES!!!
  • UV light makes melanocytes and melanosomes larger
  • Brown/Black pigment = eumelanin/elliptical melanosomes
  • Yellow/Red pigment = pheomelanin/round melanosomes
slide19
Merkel cells ~
  • Probably, touch receptors
  • Originate from neural crest at 11-12 weeks
  • Normal Merkel cells are S100+
  • Merkel tumor cells are S100-
  • Cytokeratin 20 is the marker of choice
slide20
Langerhans cells ~
  • Antigen presenting cells (present to T cells)
  • Bone-marrow derived (mesoderm origin)
  • Contain Birbeck granules (tennis racquet)
  • Markers: membrane-bound ATPase, CD1a
epidermal appendages
Epidermal Appendages
  • Eccrine glands ~
  • Regulate temperature by excreting sweat
  • Watery (merocrine) secretion
  • Everywhere except: vermilion border of lips, nail bed, labia minora, glans penis and inner prepuce
  • Markers: Succinicdehydrase, Amelophosphorylase, Leucine aminopeptidase (think: SAL)
slide23
Apocrine glands ~
  • Serve as scent glands (odorless, but bacterial action on the sweat produces odor)
  • Only in axilla, anogenital, external ear, eyelid, and breast
  • Markers: B-glucuronidase, Acid phosphatase, and NADPH (think: BAN deodorant)
slide24
Sebaceous glands ~
  • Everywhere except palm/sole
  • Holocrine secretion
  • Under hormonal control (androgens)
  • Secrete TGs, phospholipids, cholesterol, waxes
basement membrane zone
Basement Membrane Zone
  • Composed of Hemidesmosome, BM, and Anchoring Fibrils
  • Lamina lucida is composed is composed of laminin, enactin/nidogen, and fibronectin
  • Anchoring filaments: associated with laminins 1, 5, 6, and uncein
  • Lamina densa: contains Type IV collagen
  • Sublamina densa: contains Anchoring Fibrils composed Type VII collagen
dermis
Dermis
  • Papillary and Reticular
  • Helps regulate epidermal growth
  • Dermal fibroblast and epidermis interaction involves integrins
slide28
Collagen ~
  • Provides tensile strength
  • Type I: 85% of collagen in adult skin
  • Type II: found in cartilage
  • Type III: fetal skin
  • Type IV: BM collagen
  • Type V: vascular tissue
  • Type VII: component of Anchoring Fibrils
slide29
Elastin ~
  • Consist of microfibrils and matrix elastin
  • Fibrillin is a component of microfibrils
  • Oxytalan are fibers that extend perpendicularly to DEJ
  • Elaunin are fibers that extend parallel to DEJ
slide30
Ground substance ~
  • Consists of GAGs which produce proteoglycans
  • Sulfated acid mucopolysaccharides: dermatin, heparan, chondroitin, and sulfate
  • Nonsulfated: hyaluronic acid
slide31
Cells of dermis:
  • Fibroblasts
  • Myofibroblasts
  • Smooth muscle cells
  • Bone marrow derived cells: dendrocytes (APCs, Factor XIII), macrophages, mast cells
cutaneous vasculature
Cutaneous Vasculature
  • Blood supply of skin comes from subcutaneous muscular arteries
  • 3 plexi: subpapillary, perifollicular, and eccrine
  • Glomus: a special vascular structure in certain areas ~ nail bed, finger pad, volar hands/feet, ears, center of face
nerves and sensory receptors of skin
Nerves and Sensory Receptors of Skin
  • Both sensory and autonomic (primarily sympathetic) – autonomic fibers are unmyelinated
  • Sebaceous glands lack autonomic innervation
  • Sensory nerves are myelinated ~ modulate pain sensation
  • Meissner corpuscles ~ fine touch
  • Vater-Pacini corpuscles ~ pressure
hair follicle
Hair Follicle
  • Infundibulum: from the uppermost portion to the entrance of the sebaceous duct
  • Isthmus: the portion between the duct and the insertion of the erector pili muscle
  • Matrix: the lowermost part of the follicle and the hair bulb
  • The hair shaft, as well as the inner and outer root sheath, develop from the mitotically active undifferentiated cells of the matrix
slide36
The cross-sectional shape of the hair depends on the arrangement of cells in the bulb
  • Hair color depends on the distribution of melanosomes within the hair bulb
  • Black hair = Big melanosomes
  • Red hair = Round melanosomes
  • Gray hair = decreased melanocytes
slide37
Anagen (growth) ~ 3 years (90%)
  • Catagen (involution) ~ 3 weeks (1%)
  • Telogen (resting) ~ 3 months (10%)
  • Exogen (shedding)
  • Telogen = club shaped hairs (lose 50-150 per day)
  • 5 million follicles cover body at birth – no follicles form after birth, although the size of the follicle may change and is under the influence of androgens
  • Hair is composed of keratin
  • Three types: lanugo (fine), vellus, and terminal (coarse)
slide38
Follicular unit: composed of 2-4 hairs and are associated with a sebaceous gland, arrector pili muscle, and collagen
  • Average scalp density = 65-100 follicular units per cm squared
nails
Nails
  • Four structures:
  • Proximal nail fold ~ extension of epidermis that adheres to nail plate (aka cuticle)
  • Nail matrix ~ produces the nail plate
  • Nail bed ~ distal end of matrix and continues to Hyponychium
  • Fingernails grow an average of 0.1 mm/day or 3mm/month; slower for toenails
pruritus
Pruritus
  • Carried from the skin by unmyelinated C fibers
  • Hepatobiliary diseases, especially biliary obstructive disease, severe renal insufficiency, iron-deficiency anemia, endocrine disorders, and internal malignancy (especially lymphoma)
  • Thyroid dysfunction
  • Less commonly parathyroid
  • DM
  • Is typically generalized when associated with renal failure (uremic pruritus)
  • Kyrle’s disease
slide42
Pruritus of live disease
  • Hepatitis C virus infection
  • Antidepressants, belladonna, alkaloids, opiates, and oral contraceptives may induce pruritus
  • Recreational drugs (amphetamines and cocaine)
slide43
Psychiatric disease
  • Most frequently anxiety/depression
  • Or obsessive compulsive disorder
  • Treat the underlying disorder
primary lesions

PRIMARY LESIONS

Macules, patches, papules, plaques, nodules, tumors, wheals, vesicles, bullae, and pustules

tumors
Tumors
  • Soft or firm freely moveable or fixed masses
wheals
Wheals
  • Evanescent, edematous, plateaulike elevations of various sizes
vesicles
Vesicles
  • Circumscribed, fluid-containing, epidermal elevations <10mm
bullae
Bullae
  • Differ from vesicles only in size, being larger than 10mm
slide57
Nikolsky’s sign: blister shears with lateral pressure
  • Absoe-Hansen’s sign: blister shears with downward pressure
pustules
Pustules
  • Small elevations of the skin containing purulent material
secondary lesions

SECONDARY LESIONS

Scales, crusts, erosions, ulcers, fissures, and scars

scales
Scales
  • Dry or greasy laminated masses of keratin
crusts
Crusts
  • Crusts are dried serum, pus, or blood, usually mixed with epithelial and sometimes bacterial debris
excoriations and abrasions
Excoriations and abrasions
  • An excoriation is a punctate or linear abrasion produced by mechanical means, usually involving only the epidermis, but not uncommonly reaching the papillary layer of the dermis
fissures
Fissures
  • A fissure is a linear cleft through the epidermis or into the dermis
erosions
Erosions
  • Loss of all or portions of the epidermis – superficial ulceration
ulcers
Ulcers
  • Rounded or irregularly shaped excavations that result from complete loss of the epidermis plus some of the portions of the dermis
scars
Scars
  • Composed of new connective tissue that replaced lost substance in the dermis or deeper parts as a result of injury or disease
  • Hypertrophic Scar ~ confined to the area of injury
  • Keloid ~ extend past area of injury