Epidermis and Disorders of Kertatinization

Question 1

Layers of the epidermis

Answer 1

1. Stratum basalt
2. Stratum spinosum
3. Stratum granulosum
4. Stratum corneum

Question 2

Basal layer

Answer 2

Stratum basale
Cuboidal cells with proliferative function
Adhere to basement membrane via hemidesmosomes

Question 3

Spinous layer

Answer 3

Stratum spinosum
Bind to neighboring keratinocytes via desmosomes (spiny when histology ally treated)
Cells migrate to surface and lose water and flatten

Question 4

Desmoglein

Answer 4

Transmembrane proteins that connect desmosomes

Antibodies to desmogleins can lead to loss of cellular adhesion and blister formation

Question 5

Desmoglein 1

Answer 5

Localized to entire epidermis but especially in upper layers

Question 6

Desmoglein 3

Answer 6

Localized to basal layer

Question 7

Langerhans cells

Answer 7

Macrophages in epidermis
Found in spinous layer 
Derived from bone marrow
Immunomodulatory role 
Allergic contact dermatitis, graft-versus-host disease and drug eruptions

Question 8

Granular layer

Answer 8

Stratum granulosum
2-3 cells thick
Keratohyaline and lamellar granules

Question 9

Keratohyaline granules

Answer 9

Contain profilaggrin and keratin filaments

Question 10

Profilaggrin

Answer 10

Associated with intermediate filaments

Made up of filaggrin, which promotes aggregation and stabilization of int. filaments in corneum

Question 11

Lamellar granules

Answer 11

Aka Odland bodies 
Contains lipids, free sterols, hydrolases and ceramides
-barrier function 
-apoptosis
-desquamation

Question 12

Cornfield layer

Answer 12

Stratum corneum
Anucleate cells no longer mitotically active
Not on mucosal surfaces

Question 13

Lines of Blaschko

Answer 13

Linear and whirled pattern keratinocytes follow as they migrate during embryogenesis from dorsal neural crest to the ant. midline of skin and to extremities

Question 14

Keratin Structure

Answer 14

intermediate filament makes up cytoskeleton

• alpha helical structures
• 2 types: type1 (acidic) and type2 (basic)
• type1 and 2 assemble into heteropolymers, which align to form keratin filaments
• insert into desmosoems and hemidesmosomes

Question 15

Keratinization

Answer 15

aka cornification (takes 12-14 days)

• enlarge and flatten keratinocytes as migrate towards surface
• filaggrin-induced keratin filament parallel assembly and cross-linking of proteins to form cornified envelope
• release of lamellar granule lipids to form hydrophobic barrier
• degradation of cellular organelles to form anucleate cells
• apoptosis

Question 16

Desquamation

Answer 16

Shedding of corneocytes (takes 12-14 days)

• hydrolases divide proteins linking adjacent cells
• active when stratun corneum well-hydrated
• disruption results in xerosis (dry, rough, scaly skin)

Question 17

Xerosis

Answer 17

dry, rough, scaly skin

• due to decrease in intracellular lipids and NMF, failure of adherent bonds of stratum corneum to break down, and dehydration of corneocytes
• stratum corneum becomes less pliable and more susceptible to small fissures and formation of dry scale
• may req assessment of medication, renal function and overall nutritional status

Question 18

Natural Moisturizing Factors (NMF)

Answer 18

free amino acids, lactic acid, urea and salts

• hygroscopic
• accounts for pliability of the epidermis

Question 19

Atrophy

Answer 19

decreased cell proliferation

-thinning of skin

Question 20

Hyperplasia

Answer 20

increase in thickness of tissues

• Acanthosis - proliferation of stratum spinosum
• Hyperkeratosis - thickening of stratum corneum due to increase production of corneocytes or reduced desquamation
• Lichenification - thickening of stratum spinosum and corneum in response to repeated scratching and rubbing

Question 21

Wound healing

Answer 21

intermediate filaments associate with actin and tubulin, allowing the keratinocyte to migrate

• 12 hrs after wound, epidermal keratinocytes flatten and lose bond with BM and dermis
• keratinocytes migrate across wound by forming a “train”
• moist wound environment helps

Question 22

Disorders of Cornification

Answer 22

• defects in keratinocytes
• disrupted intercellular cohesion
• abnormal lipid function

Question 23

Icthyosis vulgaris (IV)

Answer 23

most common disorder of cornification

• retention hyperkeratosis
• failure of cellular signals to trigger corneocyte shedding
• autosomal dominant with variable expression
• trunk and extremities favored with fish scale
• mild itching
• commonly associated with atopic triad
• some keratosis pilaris
• hyperlinear palms
• exacerbated by cold weather and decreased humidity

Question 24

Keratosis pilaris

Answer 24

follicular retention hyperkeratosis overlying hair follicles on extensor upper and lower extremities and buttocks

Question 25

Palmoplantar Keratoderma (PPK)

Answer 25

hyperkeratosis of palms and soles - autosomal dominant AND recessive inheritance patterns - due to keratin mutations, resulting in abnormal type1 and type2 pairings of keratins - 3 categories: 1. diffuse (thick, yellow plaques of entire palm/sole, border may be red and patients may complain of hyperhidrosis) 2. focal (hyperkeratosis localized over pressure points) 3. punctate (hyperkeratotic papules and nodules, commonly misdiagnosed as warts) - treatment: pare hyperkeratotic areas and using topical moisturizers and humectants

Question 26

Diseases characterized by altered epidermis

Answer 26

increased inflammation or exposure to toxin

Question 27

Atopic Dermatits

Answer 27

eczema: common rash occurring with atopic triad (asthma, eczema, and allergic rhinitis) - genetic influence - due to increased inflammation in the skin - filaggrin defect: mutation causes loss of function, resulting in cell envelope missing protein and subsequent reduction in amino acids, causing dehydration of corneum - epidermis loses capacity for maintenance of barrier

Question 28

Psoriasis

Answer 28

inflammatory skin disease - red plaques, thick and adherent scale and nail changes - inflammation stimulates shortened cell turnover time (increased proliferation rate), with 4 day transit time - cornified layer unable to compensate, resulting in thick, erythematous plaques with adherent scale

Question 29

Staphylococcal Scalded Skin Syndrome (SSSS)

Answer 29

rare, prodome of malaise, irritability, fever and skin pain - redness starts with head then spreads - flaccid bullae develop over involved sites, followed by widespread desquamation over 3-5 days - caused by exotoxin secreted by phage group II s. aureus - Exfoliative toxins (ET-A and ET-B) target desmoglein 1 and lead to loss of cell-cell adhesion - toxins renally excreted so renal failure and immunosuppression/

Question 30

Treatment of disorders of cornification/xerosis

Answer 30

- avoid hot and prolonged showers (lukewarm water) - use mild soaps/soapless cleansers - avoid products with fragrances - do not scrub skin with washcloth nor loofah - pat dry with towel and apply emollients immediately - moisturizing creams or ointments preferred over lotions - humidifiers ma help minimize xerosis in winter - inflammatory skin diseases (eczema and psoriasis) benefit from topical steroid to reduce inflamation and allow healing of cutaneous barrier

Question 31

Emollients

Answer 31

moisturizers - topical products that hydrate skin - lotions, creams, ointments - absorb into epidermis and enhance moisture retention

Question 32

Humectants

Answer 32

agents that pull water into cells - ammonium lactate, urea creams - disorders of cornification require these