Skin Structure and Function

Question 1

What are the major skin functions?

Answer 1

barrier - resist mechanical stress, limit water loss, block entry from outside, UV shield

repair - wound healing

immunologic - tempter and alert the immune system

sensation - pain, itc, pressure, and pleasure

thermoregulation, insulation, and absorption

appearance - quality of life

Question 2

What is the makeup of the epidermis?

Answer 2

keratinizing, stratified squamous epithelium

Question 3

What is the makeup of the dermis?

Answer 3

connective tissue/stroma

Question 4

What are the four layers of the epidermis starting from the bottom? What happens in each layer?

Answer 4

basal layer (stratum basale) - proliferation

spinous layer (stratum spinosum) - adhesion

granular layer (stratum granulosum) - differentiation

stratum corneum (cornified layer) - death

Question 5

What cell types make up 90% of the epidermis?

Answer 5

keratinocytes and corneocytes

Question 6

melanocytes

Answer 6

pigment producing cells

mostly found in basal layer

directly injects melanin and pigment

Question 7

Langerhans cells

Answer 7

dendritic antigen presenting cells

important for recognizing antigen and alerting the immune system

also important in immunosuppression

Question 8

Merkel Cells

Answer 8

mechanoreceptor cells

associated with the sense of light touch discrimination of shapes and textures

often give rise to tumors

Question 9

What is the primary function of the epidermis?

Answer 9

building a semi-permeable barrier

• resist physical trauma and repair wounds
• prevent entry of noxious agents
• limit excess water loss
• protect against UV radiation from the sun

Question 10

What are the strategies for building a barrier?

Answer 10

replenish - maintain a constant supply of keratinocytes to repopulate the upper layers

resist - adopt specialized structures to yield a strong, sticky cell

release - extrude lipids and cornified envelopt to form an impermeable seal

Question 11

What are the characteristics of the epidermal self-renewal

Answer 11

normally, the epidermis turns-over every 30 days

stem cells in the basal layer give rise to proliferating compartments

basal layer cells exit the cell cycle and replenhishes the upper layer

outermost cells constantly sloughed off

Question 12

How is stratification achieved in keratinocytes?

Answer 12

asymmetrical division

different polarity of cells dividing

Question 13

What is psoriasis?

Answer 13

an inflammatory skin disease with increased keratinocyte proliferation and turnover

leads to abnormal differentiation and formation of thick, scaly plaques

Question 14

How do keratinocytes maintain their shape?

Answer 14

they build cytoskeleton networks

• microtubules
• actin-based microfilaments
• keratin-based intermediate filaments

Question 15

keratin

Answer 15

keratins are major (~25%) protein in keratinocytes

keratin composition changes as keratinocytes differentiate

54 different human keratins pair up to form intermediate filaments

subtypes are expressed in distinct epidermal cell layers

1/10 in granular/spinous and 5/14 in basal

Question 16

What are hemidesmosomes?

Answer 16

integrin-based junctions that connect basal keratinocytes to the basement membrane

mutations show generalized blistering - ex. junctional epidermolysis bullosa

Question 17

What happens in bullous pemphigoid?

Answer 17

auto-antibodies target proteins found in hemidesmosomes

these break the connection between basal keratinocytes and basement membrane -> subepidermal blisters

Question 18

What are desmosomes?

Answer 18

specialized junctions that anchor keratin to sites of cell-cell contact

genes - papkin, armadillo, and cadherins

Holds two cells together to form molecular rivets

Also allows cell-cell communications

Question 19

Lethal Acantholytic Epidermolysis Bullosa

Answer 19

disease where desmosomes are compromised (Pakin mutation)

heart and skin defomiries result

Question 20

Pemphigus Vulgaris

Answer 20

auto-antibodies target proteins found in desmosomes (cadherin)

breaks the connection between adjacent keratinocytes -> suprabasal epidermal blisters

Pemphigus Foliaceus has more superficial phenotypes

Question 21

What is the role of lamellar bodies in the skin?

Answer 21

excrete lipid for waterproof seal

Question 22

What are the “bricks and mortar” of the Stratum Corneum?

Answer 22

bricks - corneocytes

mortar - lamellar membrane

Question 23

corneocytes

Answer 23

anucleate, keratin-filled, dead keratinocytes encased in a highly crosslinked, specialized membrane - the cornified envelope

Question 24

lamellar membrane

Answer 24

lipids (ceramides, cholesterol, and free fatty acids) extruded from the keratinocytes to form a hydrophobic seal

Question 25

What skin diseases does a “leaky” barrier predispose people for?

Answer 25

ichthyosis vulgaris - caused by filaggrin mutations, leading to dr, scaly skin

many (7%) Europeans have mutations in this gene

filaggrin mutations commonly found in atopic dermatitis/exzema

Question 26

filaggrin

Answer 26

a keratin aggregating protein that is important for cornified envelope formation, hydration and barrier function

Question 27

What is the atopic march?

Answer 27

the progression of chythyosis to atopic dermatitis and then asthma/hayfever

Question 28

What is the role of tight junctions?

Answer 28

serve as a permeability barrier in simple epithelia

work in concert with the Stratum Corneum to make a barrier in skin

Question 29

What happens to the stratum corneum in atopic dermatitis (eczema)?

Answer 29

decreased FLG, LOR, INV

lipid defects

increased proeases, decreased protease inhibitors

trauma from itch-scrath cycle

Question 30

What happens to tight junctions in atopic dermatitis (eczema)?

Answer 30

decreased CLDKN1

cleavage of TJ proteins by proteases (endogenous, allergn-associated, microbe-associated)

Question 31

What is the purpose of the dermis?

Answer 31

makes up the bulk of the skin

designed for maintaining pliability and tenssile strength

Question 32

What is the composition of the matrix of the skin?

Answer 32

fibroblasts secrete different kinds of connective tissue:

• collagen fibers for tensile strength (interstitial-type I/III)
• elastic fibers - stretch and recoil, surrounded by fibrillin
• ground substance - glycosaminoclycans and fibronectin

Question 33

What happens in scleroderma?

Answer 33

an autoimmune disease where excess collagen is produced along with fibrosis

ightly packed parallel collagen bundles, which leads to destruction of lood vessels

skin appendages are absent

Question 34

What causes dystrophic epidermolysiis bulbosa?

Answer 34

mutations in Collagen VII, which anchors to the basement membrane

pliable and malleable

Question 35

What is the result of mutations int he gene producing amorphous elastin?

Answer 35

caues Cutis Laxa

skin folds and sags because of lass of recoil

Question 36

What happens fom mutations int he fibrillin 1 gene?

Answer 36

protein encases elastin

mutation leads to Marfan’s Syndrome

Question 37

What is the role of mesenchymally-derived fibroblasts?

Answer 37

the main matrix secreting cell type in the dermis

Question 38

Aside form fibroblasts, what are other cell types in the dermis?

Answer 38

dermal papilla cells - specialized fibroblasts (hair growth cycle)

mast cells - heparin and histamine release (immediate hypersensitivity, hives-urticaria)

monocyte and macrophages - phagocytic (wound healing-debris clearance)

lymphocytes (T, NKT, B cells) - immunoregulatory (inflammatory skin disease)

Question 39

What is the organization of the hair follicles?

Answer 39

epithelial origin and associated with arrector pilorum muscles and sebaceous glands

epithelial layer of the hair flollicle is is important for communication

Question 40

What are the components of the pilosebaceous unit?

Answer 40

hair follicle

sebaceous gland

arrector pili muscle

apocrine sweat glands

Question 41

What is the life cycle of a hair follicle, and what are the signals that allow it to develop?

Answer 41

dermal papilla communicates with hair follicle and stems cells to promote growth

anagen - growth

catagen - involution

telogen - rest

Question 42

What is the makeup of nails?

Answer 42

appendage of the skin that is contiguous with the surrounding epidermis and made up of keratinocytes that produce a specialized set of keratins

Question 43

What is the role of the sebaceous gland?

Answer 43

contains sebocytes that secrete their entire cell contents (holocrine secretion) into the duct

hyperactivity, hormones, bacterial colonization, and HF pligging contribute to acne

Question 44

What is the structure and function of eccrine sweat glands?

Answer 44

cool the body

stratified cuboidal epithelium

in thick and thin skin

have ducts that are directly connected to the interfollicular epidermis

Question 45

What is the structure and function of apocrine sweat glands?

Answer 45

odor-producing, found in the axilla and perineum

large lumen, secretes into hair follicle

simple cuboidal/columnar epithelium

surrounded by contractile myoepithelial cells

have ducts that directly connect to hair follicles - pilosebaceous unit