Keratinization Flashcards

1
Q

<p>Define cornification and describe list the steps.</p>

A

<p>Cornification : terminal differentiation of the keratinocyte
1) Keratinization: synthesis of fibrous proteins that compose KCs
2) Keratohyalin synthesis: i.e. protein filaggrin
3) Formation of cornified cell envelope- i.e. protein involucrin
4) Generation of neutral lipid-rich IC domains- lamellar granule secretions
5) Desquamation
</p>

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2
Q

<p>List the functions of the epidermis (7).</p>

A
<p>1) Primary function: physical permeability barrier
2) All layers prevent water loss
3) Mechanical protection, compressive &amp;amp; tensile strength
4) Protect from pathogens, UV
5) Thermoregulation
6) Sensation	
7) Wound Repair
</p>
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3
Q

<p>What are the cells of the epidermis, the percentage composition and tissue of origin?</p>

A

<p>Keratinocytes 85%, ectoderm
Melanocytes 5%, neural crest
Langerhans cells 3-8%, bone marrow (CD34+)
Merkel cells 2%, primitive epidermal cell</p>

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4
Q

<p>What is the function of Merkel cells</p>

A

<p>Slow adapting mechanoreceptor, stims HF stem cells, vasoactive controlling cutaneous blood flow and sweat, KC proliferation
Present in tylotrich pads, HF epithelium; Merkel cell tumors
Granules contain NT like substances i.e met-enkaphalin

</p>

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5
Q

<p>What are markers for Merkel cells on IHC? Which is a specific marker?</p>

A

<p>IHC: K8, K9

| K20 is Merkel cell specific</p>

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6
Q

<p>What is the thickness of the epidermis?</p>

A

<p>Dogs: 2-3 cell layers, excluding SC

| Horses: 5-7 cell layers</p>

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7
Q

<p>Describe the layers of the epidermis, function, types of keratin expressed and main anatomical features.</p>

A

<p>Basal layer: K5/14
Spinous layer: K1/10, lamellar granules, desmosomal plaques, protein kinase promotes transition to SG
Granular layer: K2/11, keratohyalin granules, [high Ca++]
Clear layer: contains eleidin, only footpad, nasal planum
SC: K1 or K2e/10, contains lamellar bilayers</p>

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8
Q

<p>Describe the concentration gradient of Ca++ in the layers of epiderims</p>

A

<p>SB: low
SS: lowest
SG: highest- Ca needed for TG activity, lamellar body exocytosis, cleavage of profilaggrin --> filaggrin
SC: very low</p>

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9
Q

<p>What is mutation of K5/14 of the SB layer called?</p>

A

<p>Epidermis bullosa simplex (EBS)</p>

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10
Q

<p>What are the 3 cytoskeletal components of the keratinocyte, relative sizes and function (brief)?</p>

A

<p>actin (7nm)</p>

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11
Q

<p>What are the functions of keratin?</p>

A

<p>Encoded by KRT-X gene

1) architecture (polarity and shape)
2) adhesion (hemi/desmosomes)
3) resist mechanical stress
4) maintain structural integrity</p>

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12
Q

<p>What are the difference between type I and II keratins</p>

A

<p>Type I: small, acidic K9-19

| Type II: basic, large K1-8</p>

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13
Q

Describe the steps of keratin assembly

A

o 1) Each keratin filament consists of a Type 1 and Type 2 keratin twisted around each other to form an α-helix heterodimer
o 2) Heterodimer w antiparallel heterodimer → tetramer.
• Assemble end-to-end → protofilaments (2-3nm)
• Assemble laterally → protofibrils (2 protofilaments = 4-5nm)
o 3) Combine until 8 heterodimers → intermediate filament
o Contains  glycine, alanine; these small aa’s allow for tight packing
o Monomer -> heterodimer -> tetramer -> protofilament -> protofibril -> keratin intermediate filament, KIF

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14
Q

What is filaggrin?

A

KIF associated protein, binds the keratin filaments and organize into macrofibrils; breakdown of filaggrin (mostly aa’s) serve as intrinsic moisturizers

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15
Q

What are the transition times of keratinocytes through the epidermis

A
Humans- 14d through epid, 14d in SC
Dog- 22d through epid
Horse- 17d
Pig- 14d
Goat- 26d
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16
Q

What is the KC cell turnover rate for a seborrheic cocker spaniel?

A

8 days

17
Q

Describe the epidermal proliferative unit (EPU)

A

o Each EPU contains 10 basal cells stacked in a hexagonal column
o Holoclone- slow cycling stem cell (<10%) in basal layer, forms
• 1) Daughter cell- remains SB stem cell, lifelong proliferation
• 2) Transit amplifying (TA) cell- (meroclone) committed progenitor, provides bulk of cell division needed for self –renewal prior to terminal differentiation
o Paraclone- Post mitotic cells fully committed and undergo term diff