Epidermis and Disorders of Keratinization

Question 1

Main functions of skin (7)

Answer 1

1. protection, 2. maintain cellular homeostasis, 3. thermoregulation, 4. immunological function, 5. pigmentation, 6. vitamin D synthesis, 7. cosmetic function

Question 2

Cells of the epidermis include:

Answer 2

keratinocytes (majority), keratin intermediate filaments (structural support), Langerhans cells (immune response), melanocytes (pigmentation), and sweat ducts.

Question 3

linear whorled pattern resulting from the migration of keratinocytes from the neural crest to anterior midline of the skin and distally to extremities. Nevi can follow these lines.

Answer 3

Lines of Blaschko

Question 4

four layers of the epidermis

Answer 4

basal, spinous, granular, cornified

Question 5

Function of basal layer of epidermis

Answer 5

proliferative layer, adherence to basement membrane by hemidesmosomes

Question 6

Function of spinous layer of epidermis

Answer 6

bind adjacent keratinocytes via desmosomes. Histo processing leads to retraction of cell walls, accentuating adjacent connections. Water lose and flattening as they move up.

Question 7

Subtypes of desmosomes

Answer 7

Desmoglein 1: in entire epidermis, concentrated in upper layers

Desmoglein 3: localized in basal layer

Question 8

Pathology in desmogleins causes:

Answer 8

loss of intercellular adherence leads to blisters.

Question 9

Cells in spinous layer

Answer 9

Keratinocytes, keratinohyaline and lamellar granules, Langerhans cells

Question 10

Function of the granular layer

Answer 10

2-3 cells thick w/ keratohyaline and lamellar granules. Keratohyaline w/ proflaggrin and keratin filaments to promote aggregation and stabilization of intermediate filaments. Lamellar granules have lipids, free sterols, hydrolases, and ceramides for release in intercellular space to serve barrier function in stratum corneum, role in apoptosis, cell organization (ceramides), and desquamation (hydrolases)

Question 11

Another name for lamellar granules

Answer 11

Odland bodies

Question 12

Function of the stratum corneum

Answer 12

thinnest stratum in genitals and eyelids, not present in mucosa, thickest in palms and soles. Site of anucleate corneocytes not mitotically active.

Question 13

Keratin types that can be combined into alpha helical structures:

Answer 13

Type 1 (acidic) and Type 2 (basic)

Question 14

Keratinization, the normal keratinocyte maturation that involves:

Answer 14

enlargement and flattening of keratinocytes migrating up, filaggrin-induced keratin filament parallel assembly and cross-linking to form cornified envelope, release of lamellar granular lipids for hydrophobic barrier, degradation of cellular organelles forming anucleate cells, and apoptosis.

Question 15

Desquamation

Answer 15

shedding of corneocytes from stratum corneum by activity of hydrolases shed in the stratum granulosum, active when skin is well-hydrated.

Question 16

dry, rough, scaly skin resulting from disruption of normal desquamation, decrease in NMFs and intercellular lipids, leading to the failure of bond breakdown and dehydration of corneocyte (forms a dry scale)

Answer 16

xerosis

Question 17

hygrosopic (water attracting) substances like free AA’s from filaggrin breakdown, lactic acid, urea, and salts that give pliability to the epidermis.

Answer 17

Natural Moisturizing Factors

Question 18

Exogenous causes of xerosis

Answer 18

dry climate, excessive (hot) water exposure, exposure to detergents or harsh soaps

Question 19

Endogenous causes of xerosis

Answer 19

atopy, ichthyosis vulgaris, renal insufficiency, lipid-lowering medicines, malnutrition

Question 20

Average transit time from basal layer to granular layer

Answer 20

12-14 days

Question 21

Average time for desquamation (sloughing off corneum)

Answer 21

12-14 days

Question 22

decreased cell proliferation leading to thinning of skin

Answer 22

atrophy

Question 23

increased thickness in skin

Answer 23

hyperplasia

Question 24

increased cell proliferation of stratum spinosum

Answer 24

acanthosis

Question 25

thickening of stratum corneum due to increase keratinocyte production or reduced desquamation

Answer 25

hyperkeratosis

Question 26

thickening of stratum spinosum and stratum corneum in response to stratching or rubbing

Answer 26

lichenification

Question 27

Process of wound healing

Answer 27

1. cytoskeletal elements as framework for cell migration
2. intermediate fibers join microfibers of actin and tubulin
3. ~12 hours after wounding, keratinocytes flatten and lose basement membrane
4. Keratinocytes “leap frog” or migrate (easiest if moist) across a wound by forming a “train”

Question 28

“Brick and mortar” model

Answer 28

Disorders of cornification resulting from defective keratinocytes, intracellular cohesion, or abnormal lipid function

Question 29

Ichthyosis vulgaris pathology

Answer 29

retention hyperkeratosis from failure of cell signaling to trigger corneocyte shedding. Most common disorder of cornification, an autosomal dominant trait.

Question 30

Clinical expression of ichthyosis vulgaris

Answer 30

dry, white, adherent scale, often in a polygonal shape. Trunk (smaller scales) and extremities (larger scales) favored. Mild itching. Sometimes w/ keratosis pilaris. Associated w/ atopy triad (atopic dermatitis, allergic rhinitis, asthma). Exacerbated by cold weather and decreased humidity.

Question 31

Follicular retention hyperkeratosis overlying hair follicles of extensor upper and lower extremities and buttocks.

Answer 31

keratosis pilaris

Question 32

Clinical expression of palmoplantar keratoderma (PPK)

Answer 32

hyperkeratosis of palms and soles. Exist as diffuse (thick, yellow plaques on entire palm/sole, border erythemous), focal (hyperkeratosis localized over pressure points), punctate (hyperkeratotic papules and nodules that look like warts). Tx: paring area, topical moisturizers to soften

Question 33

Atopic triad

Answer 33

atopic dermatitis (eczema rash), asthma, allergic rhinitis

Question 34

Pathology of atopic dermatitis

Answer 34

increased inflammation in skin from a filaggrin defect leading to predisposition to developing eczema. Mutations cause loss of function of filaggrin, cell envelope therefore missing this protein, reducing AA content as NMF for stratum corneum, so epidermis can’t form effective barrier.

Question 35

Pathology of psoriasis

Answer 35

inflammation that stimulates a shortened cell turnover time (to 4 days) from basal to granular layers, cornified layer can’t compensate and forms thick, erythematous plaques w/ adherent scale.

Question 36

Clinical expression of psoriasis

Answer 36

red plaques, thick and adherent scale, and nail changes.. Erythematous, well-demarcated plaques with thick, silvery-white scales like sheets of mineral mica. Distributed on extensor surfaces.

Question 37

clinical expression of Staph Scalded Skin Syndrome

Answer 37

malaise, irritability, fever, and skin pain (hallmark). Cutaneous erythema starts at head, generalizes. Flaccid bullae over involved sites w/ widespread desquamation over 3-5 days. Tx: hospital admission for IV antibiotics, skin care, and monitoring.

Question 38

Pathology of staph scaled skin syndrome

Answer 38

Exfoliative exotoxin secreted by phage group 2 staph aureus that target desmoglein 1 and lead to loss of cell-cell adhesion. Toxins excreted renally, so younger than 6 yr old, older, and renal failure pts at high risk. Culture from bullae negative, staph can be cultured in nasopharynx, conjunctivae, and purulent lesions.

Question 39

Treatment for xerosis and ichthyosis vulgaris

Answer 39

Avoid hot and prolonged showers and baths, use mild soaps or soapless cleaners, avoid fragrances, don’t scrub skin, pat dry and apply emollients immediately after bathing, moisturizing cream or ointments better than lotions, humidifiers in the winter.

Question 40

Topical products that hydrate skin, like lotions, creams, and ointments (increasing hydration) by absorbing in the epidermis and enhancing moisture retention.

Answer 40

emollients

Question 41

agents that pull water into cells, like ammonium lactate and urea creams. Often needed for disorders of cornification.

Answer 41

humectants