Derm - Epidermis

Front 1

3 cell populations of keratinocytes in the epidermis

Back 1

stem cells
transient amplifying cells
terminally differentiating cells

Front 2

Non-serrated keratinocytes located at the tips of rete ridges, slowly cycling cells with an infinite growth capacity that can self-replicate or generate transient amplifying cells.

Back 2

stem cells

Front 3

Serrated basal keratinocytes located along the shoulders of rete ridges and apices of dermal papillae. They have a finite growth capacity, divide more rapidly than stem cells, and can proliferate or generate terminally differentiating cells.

Back 3

transient amplifying cells

Front 4

Post-mitotic keratinocytes that enter final stages of differentiation.

Back 4

terminally differentiating cells

Front 5

Intercellular contact points between keratinocytes. Anchors for keratin filaments. Prominent in the spinous and granular layers. Important in the pathogenesis of pemphigus vulgaris and pemphigus foliaceus.

Back 5

desmosomes

Front 6

Adherence structures that connect basal keratinocytes to the dermoepidermal junction.

Back 6

hemidesmosomes

Front 7

These intermediate filaments give the epidermis flexibility and elasticity.

Back 7

keratin

Front 8

Describe keratin synthesis.

Back 8

Acid keratin or type I (K9-20) and basic keratin or type II (K1-8) assemble in pairs to form a heterodimer. They associate in an antiparallel fashion to form a tetrameric protofilament and 4 protofilaments form the final 10-nm keratin filament.

Note: This type I-type II pair is specific for different subpopulations of keratinocytes and different tissues. For example, epidermolysis bullosa simplex results from a mutation in K5 and/or K14 and epidermolytic hyperkeratosis from a mutation in K1 and/or K10.

Front 9

Desmoglein and desmocollin are what?

Back 9

Glycoproteins found in the core of desmosomes; responsible for adhesive recognition between cells.

Front 10

Which cells synthesize desmoglein and desmocollin?

Back 10

keratinocytes

Front 11

Melanocytes are derived from what?

Back 11

neural crest cells

Front 12

Langerhans cells are derived from what?

Back 12

the bone marrow

Front 13

Merkel's cells are derived from what?

Back 13

epithelial ectoderm

Front 14

Merkel's cells are important in what sensation?

Back 14

touch

Front 15

These T cells are gamma-delta.

Back 15

Dendritic epidermal T cells

Front 16

Basal keratinocytes attach to the dermis through what structures?

Back 16

hemidesmosomes

Front 17

Interdigitations of this layer with the papillary dermis provide structural integrity to the skin.

Back 17

stratum basalis

Front 18

This layer has the highest mitotic index of all the layers in the epidermis.

Back 18

stratum basalis

Front 19

Keratinocytes differentiate and proliferate in preparation for permeability barrier formation in this layer.

Back 19

stratum spinosum

Front 20

This is a layer of transition as the keratinocytes form the cornified cell envelope. Keratohyalin granules form and lamellar granules develop.

Back 20

stratum granulosum

Front 21

A colorless translucent protein present in the granules of the stratum granulosum. Also found in granules in Hassall corpuscles of the thymus.

Back 21

keratohhyalin

Front 22

A type of spherical granule in cells of the skin that migrates to the cytoplasm and discharges its contents into the intercellular space, where the granules are believed to function as a barrier against foreign substances.

Back 22

lamellar body aka keratinosome

Front 23

What are the two important granules found in the stratum granulosum?

Back 23

lamellar and keratohyalin granules

Front 24

This layer contains flat desquamating cells w/ keratin filaments embedded in matrix protein, thick cell envelopes, and lipids, which are all critical to epidermal barrier formation.

Back 24

stratum corneum

Front 25

Two terms for epidermal differentiation into stratum corneum

Back 25

keratinization
cornification

Front 26

In which layer of the epidermis are tonofilaments synthesized?

Back 26

stratum basalis

Front 27

Hemidesmosomes connect the stratum basalis to what structure?

Back 27

the basement membrane

Front 28

In which layer do tonofilaments aggregate into tonofibrils?

Back 28

stratum spinosum

Front 29

What is the primary intercellular adhesion complex in the stratum spinosum?

Back 29

the desmosome

Front 30

In this layer, lamellar granules (membrane-coating granules) and keratohyaline granules form and are discharged into intercellular space.

Back 30

stratum granulosum

Front 31

Flat dead cells which have filaments embedded in matrix protein, a thick cell envelope, and are surrounded by a lipid layer.

Back 31

stratum corneum

Front 32

What are the filaments of the stratum corneum?

Back 32

tonofibrils - made from tonofilaments - made from keratin

Front 33

This protein is composed of polypeptide chains which are arranged as a coiled-coil triple helix (alpha x-ray diffraction pattern. The triple coils are connected end-on-end through non-helical portions.) Contains many cysteine residues.

Back 33

kerain - makes up tonofilaments - make up tonofibrils

Front 34

This protein is responsible for the flexibility and elastic recovery of the stratum corneum.

Back 34

keratin

Front 35

This protein causes aggregation of keratin filaments and gives them stability.

Back 35

filaggrin

Front 36

Filaggrin is released from which granules?

Back 36

keratohyaline granules.

Front 37

This protein found in the matrix of the stratum corneum contains a histidine-rich portion and a cysteine-rich portion.

Back 37

filaggrin

Front 38

The normal plasma membrane of cells is how thick?

Back 38

80nm

Front 39

The cells of the stratum corneum have a dense marginal band just inside the plasma membrane, which is how thick?

Back 39

150-200nm

Front 40

This is the toughest material in the stratum corneum and determines its integrity.

Back 40

the cell envelope - the plasma membrane plus the dense marginal band just inside of it

Front 41

What makes the cell envelope of stratum corneum keratinocytes so tough?

Back 41

Cystine disulfide cross-links help, but what really makes it tough is the e-(g glutamyl) lysine cross link which is created by the enzyme epidermal transglutaminase.

Front 42

Which enzyme is essential for the strength of the stratum corneum?

Back 42

epidermal transglutaminase

Front 43

In which layer is epidermal transglutaminase found?

Back 43

in the stratum corneum

Front 44

What forms the permeability barrier of the stratum corneum?

Back 44

the external lipid layer

Front 45

The external lipid layer of the stratum corneum originates from which granules?

Back 45

lamellar bodies

Front 46

How long does it take a cell to go from the basal layer to the corneal layer?

Back 46

14 days

Front 47

How long does a cell stay in the corneal layer before it is shed?

Back 47

14 days

Front 48

What is the total epidermal turnover time?

Back 48

28 days (this is greatly reduced in hyperproliferative disorders such as psoriasis.)

Front 49

A group of diseases characterized by abnormal development of stratum corneum (disorder of keratinization)

Back 49

ichthyoses

Front 50

How prevalent is ichthyosis vulgaris?

Back 50

It affects 1% of the population to some degree.

Front 51

What is the genetic inheritance of ichthyosis?

Back 51

AD

Front 52

What percentage of ichthyoses are associated with atopic states?

Back 52

half

Front 53

When does ichthyosis first present?

Back 53

early to mid-childhood (not present at birth.)

Front 54

What is the initial presentation of an ichthyosis?

Back 54

dry skin and follicular keratoses

Front 55

Any horny growth, such as a wart or callosity.

Back 55

keratosis

Front 56

Areas of crusting, itching, verrucous papular growths which may fuse to form papillomatous and warty malodorous growths. Inherited.

Back 56

keratosis follicularis

Front 57

Any skin lesion in which there is overgrowth and thickening of the cornified epithelium. Approximately 20% develop into squamous cell carcinoma.

Back 57

keratosis

Front 58

Where does scaling develop in ichthyosis vulgaris?

Back 58

To a varying degree over the trunk and extensor extremities. The flexural areas are spared. Accentuation of normal palmar and sole creases is common.

Front 59

Skin bx of ichthyosis vulgaris will show what?

Back 59

Dense hyperkeratosis w/ markedly diminished or absent stratum granulosum.

Front 60

What is the epidermal transit time in ichthyosis vulgaris?

Back 60

Normal - 14 days. This d/o is due to retention of scales, not hyperproliferation.

Front 61

Ichthyosis vulgaris is due to a defect in which protein?

Back 61

filaggrin

Front 62

Defective filaggrin causes what?

Back 62

ichthyosis vulgaris

Front 63

X-linked ichthyosis is caused by a deficiency of which enzyme?

Back 63

steroid sulfatase

Front 64

How is X-linked ichthyosis diagnosed?

Back 64

enzyme studies (steroid sulfatase deficiency) or lipoprotein electrophoresis

Front 65

X-linked ichthyosis is associated with which other disorders?

Back 65

pyloric stenosis, cryptorchism, and corneal opacities

Front 66

Female carriers of X-linked ichthyosis may present with what?

Back 66

corneal opacities

Front 67

What is the distribution pattern of lesions in X-linked ichtyosis?

Back 67

The same as in ichthyosis vulgaris (trunk and extensor extremities, sparing the flexural regions) but more severe, and with an earlier onset (mild scaling may be seen at birth.)

Front 68

This AR form of ichthyosis presents at birth w/ generalized erythema and thickened stratum corneum enveloping the infant (collodion baby) which is shed shortly after birth.

Back 68

lamellar ichthyosis aka nonbullous congenital ichthyosiform erythroderma

Front 69

Eversion of the eyelids (ectropion) and the lips can occur in this form of ichthyosis.

Back 69

lamellar ichthyosis aka nonbullous congenital ichthyosiform erythroderma

Front 70

This form of ichtyosis presents w/ large, thick scales w/ raised borders and central adherence, which may have a dark gray to brown color and are widely separated. The flexural areas are involved. The palms and soles are usually thickened and scaly.

Back 70

lamellar ichthyosis aka nonbullous congenital ichthyosiform erythroderma

Front 71

Lamellar icthyosis (congenital nonbullous ichthyosiform erythroderma) can develop an extremely unpleasant odor due to what?

Back 71

colonization with saprophytic bacteria, particularly in intertriginous areas

Front 72

Does lamellar ichthyosis (congenital nonbullous ichthyosiform erythroderma) involve the scalp?

Back 72

Yes, and hair growth can be disrupted.

Front 73

Skin bx in lamellar ichthyosis (congenital nonbullous ichthyosiform erythroderma) reveals what?

Back 73

mild to moderate hyperkeratosis with a normal to thickened granular layer

Front 74

Skin bx in X-linked ichthyosis reveals what?

Back 74

hyperkaratosis with a variable granular layer

Front 75

What is the epidermal transit time in lamellar icthyosis (congenital nonbullous icthyosiform erythroderma)?

Back 75

4 days (normal is 14 days.) Excessive scaling is due in part to hyperproliferation of the epidermis (as in psoriasis.)

Front 76

What is the epidermal transit time?

Back 76

the length of time it takes for cells to go from the stratum basalis to the stratum corneum - normally 14 days

Front 77

Lamellar icthyosis (congenital nonbullous ichthyosiform erythroderma) is caused by a defect in which enzyme?

Back 77

transglutaminase

Front 78

Lamellar icthyosis (congenital nonbullous icthyosiform erythroderma) demonstrates _____ inheritance.
Epidermolytic hyperkeratosis (congenital bullous ichthyosiform erythroderma) exhibits _______ inheritance.

Back 78

lamellar - AR
epidermolytic - AD

Front 79

Epidermolytic hyperkeratosis (congenital bullous ichthyosiform erythroderma) presents how?

Back 79

Shedding of large areas of the epidermis occurs at birth, leaving a red, raw, oozing, and tender surface. Large, thick, dark scales re-form over the denuded skin and often become verrucose, particularly in flexural areas over the knees and elbows. A characteristic linear beaded pattern is often seen. Vesicles and bullae of varying sizes often develop and resolve after childhood. An unpleasant odor results from bacterial colonization.

Front 80

Shedding of large areas of the epidermis occurs at birth, leaving a red, raw, oozing, and tender surface. Large, thick, dark scales re-form over the denuded skin and often become verrucose, particularly in flexural areas over the knees and elbows. A characteristic linear beaded pattern is often seen. Vesicles and bullae of varying sizes often develop and resolve after childhood. An unpleasant odor results from bacterial colonization.

Back 80

epidermolytic hyperkeratosis (congenital bullous ichthyosiform erythroderma)

Front 81

Skin bx is diagnostic and discloses marked hyperkeratosis w/ large basophilic keratohyalin granules in a thickened granular layer. The cells of the upper epidermis are vacuolated, producing reticular spaces. The epidermis is thickened and papillomatous.

Back 81

epidermolytic hyperkeratosis (congenital bullous ichthyosiform erythroderma)

Front 82

The skin bx in epidermolytic ichthyosis (congenital bullous ichthyosiform erythroderma) demonstrates what?

Back 82

Skin bx is diagnostic and discloses marked hyperkeratosis w/ large basophilic keratohyalin granules in a thickened granular layer. The cells of the upper epidermis are vacuolated, producing reticular spaces. The epidermis is thickened and papillomatous.

Front 83

What is the epidermal transit time in epidermolytic ichthyosis (congenital bullous ichthyosiform erythroderma)?

Back 83

Reduced - 4 days (normal is 14.) This is a hyperproliferative d/o.

Front 84

Epidermolytic ichthyosis (congenital bullous ichthyosiform erythroderma) is caused by mutations in which proteins?

Back 84

kerains 1 and 10

Front 85

Which are the two main hyperprolific ichthyoses?

Back 85

Lamellar ichthyosis (nonbullous CIE)
Epidermolytic hyperkeratosis (bullous CIE)

Front 86

Which are the two main non-proliferative icthyoses?

Back 86

icthyosis vulgaris
X-linked ichthyosis

Front 87

What are the important ddx of icthyosis?

Back 87

psoriasis
exfoliative dermatitis (a generalized rash which is red and scaly, can be from many causes)
icthyosis-like change due to internal malignancy

Front 88

How do you treat non-proliferative icthyoses (icthyosis vulgaris and X-linked ichthyosis?)

Back 88

Hydration of skin followed by emollient application
Removal of scales: Creams and lotions containing lactic acid, salicylic acid and/or urea help remove excess keratin from the S. corneum (keratolytics). 40-60% aqueous preparation of propylene glycol under plastic occlusion overnight, 2-3 x/week

Front 89

How do you treat hyperproliferative icthyoses (lamellar/nonbullous CIE; epidermolytic/bullous CIE)?

Back 89

13-cis-retinoic acid
5-10% lactic acid ointment daily
systemic antibiotics and antiseptic soaps to remove bacterial flora and their odor

consider: cytotoxic agents such as MTX (but not in children), isotretinoin (not approved for long-term use.)

Front 90

What is acquired ichthyosis?

Back 90

Icthyosis that first presents in an adult. Usually due to internal malignancy, but can be due to drugs or other diseases.