Structure and function of the skin Flashcards

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1
Q

The primary keratinocyte intercellular junction is the:

A

Desmosome

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2
Q

Desmosomes connect to keratinocytes by anchoring onto:

A

Keratin

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3
Q

Desmosomes consist of ______ which are cytoplasmic, and ____ which are transmembrane

A
  • Desmoplakin, plakophilin, plakoglobin.

- Desmocollin 1/2/3, and desmoglein 1/3

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4
Q

Desmocollin, desmoglein and other cadherins are dependant on _____ to function

A

Calcium

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5
Q

Adherence junctions function to_____ by anchoring/attaching to ______

A
  • mediate tight intercellular binding

- Actin filaments

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6
Q

Tight junctions are made up of ______. They function to________

A
  • claudins and occludins

- form tight seal against water loss in granular layer

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7
Q

Gap Junctions function is _______. They are composed of _______.

A
  • intercellular communication

- Connexons which are made of 6 connexins

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8
Q

Which keratins are produced in stratum basale

A

5+14

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9
Q

Cellular proliferation in the stratum basale is stimulated by:

A

trauma, UV radiation (increased ornithine decarboxylase expression is associated with proliferative states)

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10
Q

Ornithine decarboxylase is inhibited by:

A

Retinoids, corticosteroids, Vitamin D3

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11
Q

What percentage of cells in the basal level are stem cells?

A

10%

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12
Q

Transit time from basal layer to SC is? And from SC to desquamation?

A

14 days, and another 14 days

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13
Q

Function of stratum corneum is:

A

mechanical barrier

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14
Q

Structure of stratum corneum:

A

protein rich corneocytes with no nuclei (bricks) and lipid matrix (mortar)

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15
Q

______ are the intermediate filaments that comprise the primary cytoskeleton of the epidermis

A

Keratins

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16
Q

Type I Keratins have _____ molecular weight

  • are (acidic/basic)
  • K#______
  • chromosome #______
A
  • Low molecular weight
  • acidic
  • K9-28, K31-40 (hair keratins)
  • chromosome 17
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17
Q

Type II Keratins have _____ molecular weight

  • are (acidic/basic)
  • K#______
  • chromosome #______
A
  • high molecular weight
  • basic
  • K1-8, K81-86 (hair keratins)
  • chromosome 12
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18
Q

Functional unit of keratin:

A

heterodimers of type I and type II filaments that form tetramers and ultimately filaments

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19
Q

Keratin is anchored to plasma membrane by:

A

desmosomes

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20
Q

Keratinocytes produce which IL’s and what other molecule?

A

IL-1,6,8,10,12 and TNF alpha

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21
Q

Melanocytes are derived from ______

A

neural crest

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22
Q

Activation of what molecule is required for melanocyte development/migration?

A

C-kit

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23
Q

Piebaldism occurs as a result of____

A

loss of C-kit–>impaired melanocyte migration and proliferation

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24
Q

Mutations of C-kit are associated with____

A

acral and mucosal melanoma

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25
Q

Each melanocyte interfaces with ___ keratinocytes?

A

36

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26
Q
  • Melanin is produced in _____ from its precursor _____.

- this process involves a copper dependent enzyme _____

A
  • melanosomes, tyrosine

- Tyrosinase

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27
Q

Pheomelanin color:

Eumelanin color:

A
  • red/yellow

- black/brown

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28
Q

Difference in skin color is due to differences in:

A
  • melanosomes
  • in darker individuals are larger and have more melanin
  • Melanosomes are more stable and are transferred individually in dark skin (light skin are smaller, lighter, and less stable
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29
Q

Melanin production is stimulated by _____ and _____ on _____ on melanocytes

A
  • melanocyte-stimulating hormone (MSH)
  • ACTH
  • on MC1-R
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30
Q

MC1-R loss of function mutations—->_____ and phenotype of ____

A
  • increased pheomelanin:eumelanin ratio
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31
Q

Reason that darker skin types are “protected” more from the sun?

A
  • Melanin absorbs UV and protects against UV induced mutations
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32
Q
  • Immediate tanning is due to_____

- delayed tanning is due to____

A
  • oxidation of existing melanin

- new melanin synthesis

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33
Q

Oculocutaneous albinism is due to:

A

defects in enzymes required to convert tyrosinase to melanin

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34
Q

Defects in packaging of melanosome-specific proteins leads to which syndrome?

A

Hermansky-Pudlak (Hermansky Pudlak Hates Packaging melanosome proteins)

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35
Q

Defects in lysosome and melanosome trafficking to dendrites leads to ___ syndromes (2 different syndromes)

A
  • Griscelli
  • Chediak-Higashi syndrome
    Griscelli and Chediak-Higashki are not good traffickers along the dendrite highway
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36
Q

Major antigen presenting cell of the skin is the ____

A

langerhan cell

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37
Q

Describe the form of a langerhan cell:

A
  • reniform (kidney shaped) nuclei

- tennis racket shaped Birbeck granules seen on EM

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38
Q

Positive immunostains for Langerhan cells:

A
  • CD207 (Langerin), CD1a, S100, CD34, Vimentin,

Actin

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39
Q

Layer of skin where langerhan cells do work:

A

Stratum spinosum “L”

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40
Q

What do langerhan cells do after encountering and processing an antigen in the stratum spinosum?

A
  • migrate to lymph nodes and activate T-cells
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41
Q

What down-regulates langerhan cells?

A
  • UV exposure
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42
Q

Merkel cells are (slow/fast?) adapting mechanoreceptors and are found in _____ parts of body, and ____ layer of skin. They communicate with ____.

A
  • slow adapting mechanoreceptors
  • fingertips, lips, oral cavity, hair follicles
  • stratum basale
  • communicate with neurons
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43
Q

______ marker/pattern is sensitive and specific for merkel cells?
- Merkel cells are also positive for_____

A
  • CK20+ in perinuclear dot pattern
  • also positive for neurofilaments, S100, synaptophysin, chromogranin A, vasoactive intestinal peptide, neuron-specific enolase, and calcitonin gene-related peptide
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44
Q

Semipermeable barrier between epidermis and dermis that also serves to adhere basal keratinocytes to underlying dermis is the ______

A

basement membrane zone

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45
Q

Basement membrane zone:

- Describe the connection between basal keratinocyte and hemidesmosome.

A
  • intracellular keratin filaments K5 and K14 attach to hemidesmosomal plaques (plectin and BPAG1) on basal plasma membrane.
  • hemidesmosomal plaque proteins bind to intracellular portions of the anchoring filaments (BPAG2 and alpha 6 Beta 4 integrin)
  • see diagram in book (pg 6)
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46
Q

Basement membrane zone:
- the extracellular portion of anchoring filaments (BPAG2, alpha 6 beta 4 integrin, and laminin 332) that extende from hemidesmosome down to lamina densa is the _____

A
  • lamina lucida

- see diagram in book (pg 6)

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47
Q

____ is the weakest portion of basement membrane zone.

- this is the zone of separation in which two disorders?

A
  • lamina lucida

- salt-split skion and suction blisters

48
Q

Basement membrane zone:
- anchoring filaments in lamina densa attach to _____ which results in attachment between basal keratinocyte and lamina densa.

A
  • Type IV collagen

- see diagram in book (pg 6)

49
Q

Basement membrane zone:

- Describe structure of sublamina densa

A
  • loops of type VII collagen arise from underside of lamina densa, extend down into dermis, hook around dermal type I and IIIO collagen fibers, then loop back up to reattach to lamina densa
  • this firmly anchors lamina densa to papillary dermis
50
Q

Basement membrane zone functions to adhere basal keratinocytes to underlying dermis, AND as a permeability barrier mainly due to _____

A
  • negatively charged heparan sulfate proteoglycan in the lamina densa
51
Q

Dermis is derived from _____ and divided into what layers?

A
  • dermis derived from mesoderm

- superficial papillary, and deep reticular dermis

52
Q
  • Fibroblasts are located in which layer of skin?

- what are the two general functions of fibroblasts?

A
  • fibroblasts are located in the dermis

- fibroblasts create extracellular matrix and are involved in wound healing.

53
Q

Glomus cells are specialized_____ cells that are derived from ______.

A
  • smooth muscle cells
  • Sucquet-Hoyer canals
  • “suck it Hoyer! i got these smooth glumus cells”
54
Q

Sucquet-Hoyer Canals (help to form glomus) allow for shunting of blood from _____ to _____, and are found mainly in which parts of body?

A
  • From arterioles to venules (bypassing capillaries)
  • palms/soles (this is why glomus tumor favor acral sites)
  • “Suck it Hoyer! i got these smooth glomus cells in the palm of my hand”
55
Q

Overproduction of glomus cells leads to ____, which most commonly occurs in which part of body?

A
  • glomus tumor

- palms and soles (because glomus cells are mostly found in palms and soles)

56
Q

Function of dermal dentritic cells:

A
  • highly phagocytic cells
57
Q

Extracellular matrix function:

A
  • provides structure and support to the dermis; essential for water retention and for signal transduction
58
Q

Extracellular matrix is composed of:

A
  • collagen
  • elastin
  • fibrillins
  • fibulins
  • integrins
  • laminins
  • glycoproteins
  • proteoglycans
59
Q

Describe the structure of collagen

A
  • triple helices formed by amino acid chains where every third residue is glycine-X-Y, with X and Y most likely being proline and hydroxyproline/hydroxylysine respectively.
  • “C” for Collagen is third letter in alphabet, every THIRD residue is glyCine
60
Q

____ accounts for 75% of dry weight of the skin and is #1 component of the dermis

A
  • Collagen
61
Q

Primary collagen of the extracellular matrix is____

A
  • Type I
62
Q

____ and _____ catalyze crosslinking of collagen

A
  • Lysyl hydroxylase

- Proline hydroxylase

63
Q

Crosslinking of collagen depends on _____, deficiency leads to _____

A
  • Vitamin C

- Scurvy

64
Q

Defects in collagen and/or collagen cross-linking results in most forms of _____

A
  • Ehlers Danlos syndrome (see page 7 for specifics)

- Ehlers Danlos cant cross-link collagen

65
Q

____ degrades collagen

A
  • matrix malloproteinases
66
Q

____ increases collagen

A
  • Retinoids
67
Q

____ and ____ decrease collagen

A
  • corticosteroids

- UV

68
Q

Terminal keratinocyte differentiation is secondary to increased ____ in supra;basal epidermis

A
  • intracellular calcium
69
Q

Odland bodies (lamellar granules) are produced in which layer of skin, and primarily contain _____

A
  • Spinous layer

- ceramides

70
Q

____ are specialized lysosomes that dishcarge ceramides in stratum corneum

A
  • odland bodies/lamellar granlues
71
Q

_____ help to form the cornified cell envelope

A
  • ceramides
72
Q

Two diseases that are secondary to decreased lamellar granules (odland bodies) are :

A
  • Flegels disease
  • Harlequin ichthyosis
  • Flegel and Harlequin are odd guys
73
Q

stratum granulosum has prominent basophilic keratohylaine granules which contain____

A
  • profilaggrin, loricrin, and involucrin
74
Q

Cornified cell envelope production takes place primarily in which layer of skin

A
  • granular
75
Q

number one component of cornified cell envelope is _____

A

Loricrin

76
Q

Cross linking of proteins and lipid of cornified cell envelope occurs via_____

A

transglutaminase I

- this is the “glue” for the cornified cell envelope

77
Q

elastic fibers of skin are made up of 90% ____ and 10% ____

A
  • 90% elastin (core)

- 10% fibrillin (surrounds elastin)

78
Q
  • desmosine and isodesmosine are found in high levels in ______
A
  • elastin
79
Q

desmosine and isodesmosine, which are found in high levels in Elastin, crosslink with fibrillin via ____

A
  • lysyl oxidase
80
Q

lysyl oxidase, which helps in the crosslinking of elastin, requires ____ for function

A
  • copper
81
Q

fibrillin 1 mutation of elastic tissue=

A

Marfans

82
Q

fibrillin 2 mutation of elastic tissue=

A

Congenital contractural arachnodactyly

  • 2 C’s- congenital contractural
83
Q

Fibulin 5 defect of elastic tissueleads to _____

A

Cutis laxa

- cutis laxa is a liar who fibbed 5 times!

84
Q

ABCC6 mutation in elastic tissue leads to ____

A

pseudoxanthoma elasticum (fragmentation and calcification of elastic fibers

  • psuedoxanthoma elsasticum….ABC news
85
Q

Elaunin fibers in elastic tissue run ____ in reticular dermis and oxytalan fibers run ____ to DEJ in papillary dermis

A
  • horizontal/parallel in reticular dermis
  • vertical/perpendicular in papillary dermis
  • mnemonic: “stand (vertical) up-high (high in dermis) with OXYgen (oxytalan)
86
Q

Fibers in elastic tissue are set in a matrix of ____ and ____ which retain large quantities of _____. This is called ______

A
  • proteoglycans and glycosaminoglycans
  • retain large quantities of water (up to 1000x’s their volume!)
  • ground substance
87
Q

Most important glycosaminoglycan is _____

A
  • hyaluronic acid ( in addition to chondroitin sulfate, dermatan sulfate, and heparan sulfate)
88
Q

Two vascular plexuses of skin are_____ and _____

A
  • superficial (vessels of reticular dermis

- deep (vessels of follicles and glands)

89
Q

primary mediator of vasculogenesis in skin is _____

A
  • VEGF
90
Q

Name the four lymphatic vessel markers

A
  • Prox1
  • Podoplanin
  • LYVE-1
  • VEGFR-3
91
Q

Free nerve endings of skin sense ____ and ____

A
  • Itch and pain
92
Q

Krause end bulb are specialized nerve receptors located where?

A
  • genitalia, perianal region, vermillion lips

- Krazy Krause ends on erotic areas

93
Q

Meissner’s corpuscle are ____ (fast/slow) adapting nerve receptors, they are _____ (deep/superficial) they are located on the _____ and are suited for which type of sensation?

A
  • fast
  • superficial
  • on the digits
  • pressure/LIGHT touch
  • meiSSner= Speed, Superficial
94
Q

Merkel nerve endings are located ____ (superficial/deep), concentrated in which regions of body, are ____ (fast/slow) adapting, and best suited for ____

A
  • superficial (basal layer of epidermis)
  • concentrated in fingertips, lips, external genitalia
  • slow adapting
  • suited for pressure/touch
95
Q

Ruffini corpuscle nerve endings are located____ (deep/superficial). concentrated around _____, are ____ (fast/slow adapting) suited for _____

A
  • deep, in the fat (deep in the rough- golf)
  • concentrated around fingernails
  • slow adapting
  • sustained pressure (he hits into the rough when hes under sustained pressure, and is slow to get out)
96
Q

Pacinian corpuscel nerve endings are mechanoreceptors located ____ (superficial/deep) are located ______, are ____ (fast/slow) adapting and suited for ____.

A
  • deeP
  • Palmoplantar skin, niPPles, genital region
  • fast adapting
  • vibration and deeper pressure
97
Q

Vascular smooth muscle, apocrine glands, and arrector pili contraction are under ____ (adrenergic or cholinergic) control

A
  • Adrenergic

- vAscular, AApocrine, AArrector pili

98
Q

Eccrine glands are under ___ ( adrenergic or cholinergic) control

A
  • Cholinergic

- eCCrine, CCCholinergic

99
Q

Eccrine glands function to :

A
  • thermoregulate and excrete waste
100
Q

Eccrine glands are found on all skin surfaces except ____

A

external auditory canal, lips, glans penis, clitoris, and labia minora

101
Q

Highest concentration of eccrine glands are on ____

A

palms and soles

102
Q

Eccrine glands are innervated by ____ which synapse with ____ acetylcholine receptors on the glands

A
  • postganglionic sympathetic fibers

- muscarinic (this is why botox decreases sweat . by inhibiting Acetylcholinesterase)

103
Q

sweat is (hyper or hypotonic) on skin surface

A
  • hypotonic (NaCl gets reabsorbed)
104
Q

Eccrine glands stain for ____

A
  • S100, Keratin, CEA
105
Q

Apocrine glands are located ____

A
  • Anogenital region, Axillae, external Auidotry canal, Areola of nipple, eyelid margin
  • remember the A’s of Apocrine glands
106
Q

Secretory products of apocrine glands are released through process of ______, and include ___

A
  • decapitation secretion
  • cholesterol, triglycerides, squalene, fatty acids
  • decapitate the smelly stuff
107
Q

____ is pigmented mixture of lipids and proteins secreted by apocrine glands responsible for yellow-brown color of chromhidrosis

A
  • Lipofuscin

- Lipofuscin makes your t shirts yeLLow

108
Q

Ectopic or modified apocrine glands include :

- these empty directly to ___

A
  • mammary glands, ceruminous glands of external auditory canal, and Moll’s gland of the eyelids
  • surface of skin
109
Q

Sebaceous glands are found primarily on:

A
  • scalp, face, upper anterior trunk
110
Q

Sebaceous glands are NOT found on the:

A
  • palms/soles
111
Q

Sebacous glands are normally associated with a ____

A
  • hair follicle
112
Q

Sebaceous gland maturation is signaled by _____

A
  • pubertal androgen production
113
Q

Which type of secretion do sebaceous glands secrete?

A
  • Holocrine secretion
114
Q

Sebum contains mostly ____ in addition to_____ and ____

A
  • Triglycerides (50%)
  • wax esters
  • squalene
115
Q

Name the ectopic sebaceous glands and their location

A
  • Meibomian glands- eyelid
  • Fordyce spots- vermillion lip
  • montgomery tubercles- areola/nipples- on the titties
  • Tysons glands- labia minora/prepuce
  • Zeis glands- eyelid margin