Dermatology skin biology Flashcards
(164 cards)
1
Q
structure of the epidermis in order 5
A
strateum corneum (horny cell layer) granular cell layer (strateum granulosum spindle cell layer (stratum spinosum) basal layer (stratum basale) basement membrane
2
Q
2 layers of the skin
A
epidermis
dermis
3
Q
what type of epithelium is skin
A
squamous epithelium
4
Q
main cell of the epidermis is
A
keratinocytes
5
Q
main cell of the dermis is
A
fibrolasts
6
Q
what other cell types are in the epidermis
A
- langerhans cells
- melanocytes
- merkel cells
7
Q
what are langerhans cells
A
bone marrow derived macrophages
antigen presenting cells
immunology involved
8
Q
what are melanocytes
A
neural crest derived pigment producing cells
9
Q
what are merkel cells
A
neuroendocrine cells that are assoc. with particular nerve endings in the epidermis
10
Q
what cells are in the dermis
A
fibroblasts
mast cells
inflammatory cells
vessels
11
Q
what makes up the acellular material of the dermis
A
collagen
elastin
glycosaminoglucans
12
Q
what are fibroblasts
A
mesenchymal derived cells
chief function is the production and remodelling of the extracellular protein collagen
13
Q
what are mast cells
A
type of tissue basophil
contain and degranulate a range of vasoactive chemicals including histamine
14
Q
what inflammatory cells are found in the dermis
A
lymphocytes
polymorphs
range of dermal macrophages and antigen presenting cells
15
Q
what are the appendageal structures
A
hair follicles
sebaceous glands
eccrine glands
apocrine glands
16
Q
from what are appendageal structures derived from
A
all epidermal derived
arise during embryonic development at end of 1st trimester
17
Q
when do new appendageal structures stop being formed
A
cant be formed after the early second trimester
18
Q
what is a pilosebaceous unit
A
=sweat gland and hair follicle
19
Q
components and physiology of the basal layer in the epidermis
A
- basal cells are cuboidal keratinocytes that sit on the basement membrane
- one cell layer thick
- also contains stem cells which undergo division
20
Q
process of stem cell division in basal layer
A
- stem cells undergo asymmetrical cell division to form another stem cell and a transient amplifying cell
- the transient amplifying cell can then undergo several rounds of division and finally form a terminally differentiated keratinocytes that moves into the spindle cell layer
21
Q
where are the two pools of keratinocyte stem cells in skin and why are there two
A
- basal layer- interfollicular stem cell pool
- in the hair follicle close to where the sebaceous gland joins
the 2nd repopulates the first if the first is removed
22
Q
spindle cell layer anatomy
A
also called prickle cell layer because the tight desmosomal attachments between cells
23
Q
granular layer
-what is the granular layer made up of
A
- keratohyalin= protein filaggrin and keratin
- lipid lamellae= intraceullar membrane bodies which discharge epidermal lipids into the intercellular space in the high epidermis-lipid extrusion
24
Q
skin keratin expression basal layer vs spindle cell layer
A
- basal layer expresses keratin 5 and 14
- spindle layer expresses k1 and k10
- so when skin is wounded different keratins are expressed
- so get different phenotypes depending on what is wounded
25
stratum corneum
| what is it made up of
-made up of multiple layers of flattened keratinocytes called "cornified envelopes" (corneocytes)
26
process of keratinocytes death and desquammation 7
1. cornified envelopes begin to form in the granular layer
2. the plasma membrane is replaced by covalently cross linked proteins including keratins and fillagrin
3. this is done by the enzyme transflutaminase
4. these are dead keratinocytes with no nucleus
5. individual (squames) dead cells of the stratum corneum eventually break off and fall into surroundings= desquammation
6. desquammation relies on a protease mediated breaking down of the desmosomes
7. skin then falls off
27
what do keratinocytes do 3
make keratin and fillagrin
| make lipids
28
keratinisation
process of stem cell differentiation into keratinocytes
29
dead keratinocytes
cornoecytes
30
what aggregates keratin together
fillagrin
| =keratohyalin granules
31
what do keratins do
structural proteins that provide physical support for the cell
- they are dynamic structures that change as cells divides
- produce keratins, fillagrin, granules and lipids
32
how do keratinocytes attach
-keratin attach to the desmosomes, points of cell adhesion between keratinocytes
33
how does the skin thicken in response to frictional forces
-frictional forces on the skin provoke thickening of the epidermis- by increase in proliferation of basal layer and an increase in daughter cells moving up into the spindle cell layer
34
what is acanthosis
=thickening of spindle cell layer
35
what is hyperkeratosis
=thickening of stratum corneum
36
what does the brick and mortar model replicate
brick=individual dead keratinocytes in stratum corneum cross linked and aggregated keratins
mortar= lipid
=hydrophobic barrier
37
disturbance of skin barrier- causes 3
- irritant dermatitis= eg household cleaners attack the hydrophobic lipid barrier
- atopic dermatitis =disorder of barrier function
- mutation of filaggrin= filaggrin helps to bundle keratinocytes into the cornified envelope - so dont form a proper cornified envelope
38
why is disturbance of skin barrier a positive feedback mechanism
because the more the barrier is destroyed the more acids/ harmful substances can get through which cause more destruction allowing more acids through
39
why is filaggrin called filaggrin
filament aggregating protein- bundles up keratinocytes
40
what does transglutaminase do
responsible for covalently crosslinking to form the cornified envelope
41
what do mutations in transglutaminase cause
lamellar icthyosis-scally skin
42
how can oestrogen penetrate the skin
it is lipid soluble
43
what are the embyrological origins of keratinocytes and melanocytes
ectoderm and neural crest respectively
44
two types of melanin
```
eumelanin= brown or black
pheomelanin= red or yellow
```
45
ratio between melanin means
determines skin and hair colour
-if mostly pheomelanin= mostly red hair
eumelanin= black hair
small amounts of both= yellow
46
how is melanin produced
1. produced by melanocytes
2. toxic to cells so made in melanosomes
3. melanosomes are passed down the denrities of the melanocytes into the surrounding keratinocytes
47
what does melanin do
protects the skin from UV ratio
48
what is albinism
| - main gene
genetic disorders in which the amount of melanin produced is reduced
- number of melanocytes is normal
- most common type is due to recessive mutation in the gene for tyrosinase a key enzyme in melanin production
49
other pigments contributing to skin colour are
```
melanin
haemoglobin
bilirubin
pigment from drugs or heavy metals
foods eg carotenoids
```
50
what are the more common cancers derived from epidermis or dermis
mostly from epidermis
| UVR load is higher
51
langerhans physiology
- antigen presenting cells
| - when there is an antigen they present it to T cells in the regional lymph node
52
what cells are involved in mechanoreception
merkel cells
53
what makes up the basement membrane
-aceullular
| proteins
54
what attaches basal keratinocytes to the basement membrane
hemidesomosomes
55
what disease targets hemidesmosomes
bullous pemphigoid
56
two layers of the dermis
superficial papillary dermis
| deeper reticular dermims
57
what vitamin is essential for normal collagen production and what disease and presentation do you get without it
vitamin c
| scurvy= corkscrew hairs, perifollicular haemorrhage, gingivitis
58
what synthesises collagen
fibroblasts
59
dystrophic epidermolysis bullosa is due to
mutations in collagen VII
60
ehlers danlos is due to
mutations in a range of collagens
61
solar pupura is caused by
| and pathophysiology
-steroids use- reduces amount of collagen
-ageing and UV exposure
due to changes in collagen biosynthesis and remodelling
62
what does solar pupura mean
easy bruising
| reduced collagen- reduced dermal thickness
63
function of collagen in dermis
provides a padding around dermal vessels to help prevent bruising
64
main elastic fibres
fibrillin
65
main glycosaminoglycans of the skin 4
hyaluronic acid
heparin sulfate
chondroitin sulphate
keratin sulphate
66
function of mast cells
- they contain histamine, prostaglandins, leukotrienes and cytokines
- grouped in granules
- tissue basophils
- trigger causes mast cell degranulation which releases mediators such as histamine
67
type 1 hypersensitivity pathophys
eg allergy anaphylaxis
| IgE crosslinks to mast cells
68
what is the archetypal clinical lesion of mast cell degranulation
weal
69
desmographism
drawing on skin
70
what is the triple response to histamine 3
1. initial erythema close to site
2. larger flare of erythema
3. collection of dermal oedema= weal
71
triple response what causes the initial erythema
direct effect of histamine on vessel walls
72
triple response what causes the larger flare of erythema
axon reflex
stimualtion by histamine of peripheral nerves is transmitted along sensory nerve and travels backwards along other sensory nerves causing release of mediators at distal nerve endings resulting in vasodilation- antidromic stimulation
73
triple response what causes weal
transient increase in permeability in small vessels causing local oedema until fluid reabsorbed
74
urticaria
mast cell degranulation disease
75
what makes up appendageal structures
keratinocytes
| except dermal papilla of hair follicle has specialised fibroblast
76
eccrine sweat glands - where are they not present
lips or external ear canal
77
what innervates eccrine glands
cholinergic post ganglionic fibres of sympathetic nervous system
78
2 main functions of sweating are
1. evaporative cooling
| 2. frictional grip - on the palms
79
production of sweat
- secreted into lower secretory portion of eccrine gland as an isotonic fluid
- gradually it changes to a hypotonic fluid by selective reabsorption of salt as the duct moves through the skin
80
apocrine (sweat) glands function
- assoc. to sites such as axilla, nipples and groin
- bacterial decomposition is what causes the odour
- androgen sensitive
81
sebaceous gland function
production of lipids that make up sebum
82
what is sebum
made up of trig, fatty acids, squalene and cholesterol
83
where are sebaceous glands mostly found
scalp face and upper chest
| hence acne
84
what increases sebum production and what decreases
- androgens
- progestogens
-oestrogens decrease sebum production
85
what makes up a hair follicle
central medulla
cortex
outer curicle
86
3 main types of hair
lanugo hairs
vellus
terminal hairs
-sexual hairs are subset of terminal
87
lanugo hairs
fine hairs seen only on premature infants
no medulla
soft
no pigment
88
vellus
hair are normally short and very thin
no medulla and lack pigment
found all over the body postnatally
comprise the majority of hairs eg most facial hair inn women
89
terminal hairs
long thick pigmented hairs with a central medulla eg scalp and eyelashes
90
what makes sexual hairs
androgens acting on vellus hairs
91
3 phases of the hair cycle
anagen
catagen
telogen
92
anagen is
growth phase which lasts about 3 years for scalp and 3-4 months for chest
93
catagen
3 week transitory period in which each hair bulb undergoes apoptosis and regression in which the lower part of the hair moves up close to the skin surface
94
telogen
period lasting approx 3 months in which the hair is relatively quiescent
then the new hair pushes out the old one, which is shed
95
nail structure
nail plate
nail bed
nail matrix
96
nail plate
hard material of nail
| made up of dead keratinocytes
97
nail bed
found under the nail plate contributes slighlty to the growth of the underside of nail
98
nail matrix
-main growth zone of nail
| extends from proximal nail fold to the end of the lunula endpoint
99
sensory nerve supply to skin
| -2 functions
- only sympathetic nerves
- no parasympathetic supply to the skin
1. eccrine sweating
2. vascular tone
100
erythroderma
inflammatory disease where increased blood flow to the skin
- so skin appears red all over and hot
- but actually they have central hypothermia
- concealed hypothermia
101
arrector pilli smooth muscles function
- goosebumps
- sympathetic control
- no function in humans
102
pruritus definition
sensation that derives need to scratch
103
itch pathway
- itch receptors are found both dermis and epidermis
- conducted along unmyelinated c fibres
- cross over in the spinothalamic tract and synapse to neurons that mediate itch scratch reflex
- no single itch centre in brain
104
main triggers of itch 2
histamine
| non histamine mediated pathways eg protease activated receptors PAR
105
alloknesis means
describes how the skin around the central focus also appear to be itchy when it is lightly touched
- reflects reinterpretation of light touch as an itch at the level of the spinal cord (A fibres)
- allodynia same for pain
106
interactions between pain and itch
- scratching can cause pain which then masks itch
| - opioids diminish pain but may provoke itch - inhibitory pathways on each other
107
chronic presentation of itch 2
1. lichenification
| 2. nodular purigo if nodules of itch
108
complication of scabies infestation
- strep systemic infection and death
| - hence scratch to try and remove mites
109
how do antihistamines help for an itch which is mediated by non-histamine mediators eg atopic dermatitis (like most are)
- antihistamines are sedatives on central CNS effects which results in less scratching
- so reduction in scratch is not due to peripheral histamine blockade but due to sedation
110
can histamine induce pain and itch
histamine applied superficial to skin get mostly itch but if injected then get pain
111
what disorders is itch mediated by histamine
urticaria
112
what disorders is the itch not mediated by histamine
atopic dermatitis
psoriasis
lichen planus
113
are scratch marks usually same size
larger on back as nerve fibre density and 2 point discrimination is not as good
114
type 1 hypersensitivity reaction
-immediate <20 mins
-reaction is mediated by crosslinking of IgE molecules on mast cells by allergens
-results in degranulation of mast cells and the clinical lesion is urticaria
-also seen in demographisms- histamine in response to pressure
degranulation can also occur by non-immune methods
115
peanut allergy patho
peanut antigen cross links IgE bound to mast cells in the skin and mucosae
get urticaria
peanut antigen can also provoke a response via systemic absorption or via mucosae if very sensitive
116
latex allergy patho
eg seen in surgical gloves
IgE mast cell
intense itching and swelling of hands
117
inx for hypersensitivity type 1
- hx
- serum specific IgE measurement to antigens= RAST - safer and preferred method of testing
- skin prick testing
118
pathophysiology chronic immune urticaria
the crosslinking of IgE is by an autoreactive IgG molecules
119
type II hypersensitivity path and examples
IgG antibody mediated cytotoxicity
| examples include pemphigoid and pemphigus and systemic vasculitis involving ANCA
120
type III hypersensivity and example
this is where immune complexes form and deposition of these complexes in the vessel may lead to a series of changes including complement activation, and activation of polymorphs and macrophages,
and subsequent tissue damage to vessels surrounding tissue
example is leucocytoplastic vasculitis which can be response to drugs, infection, or SLE/ RA
121
type IV hypersensitivity -delayed
T cell mediated reaction
clinically presents as eczema- dermatitis
eg nickel allergy, or allergic contact dermatitis in response to a plaster
122
nickel allergy presentation
contact allergic eczema
type IV
20% of the population
means prior exposure to the nickel antigen to skin has resulted in presentation of t cells and development of immune memory
get eczema where skin comes into contact with nickel
24-96 hrs
123
how to inx type 4 hypersensitivity
patch testing
| -in which the skin is exposed under controlled conditions to a range of likely antigens
124
type 4 vs type 1 hypersensitivity
type 4
- use patch testing
- eczema appearance
type 1
- use skin prick test
- urticaria appearance
125
3 main types of electromagnetic radiation
ultraviolet radiation
visible light
infared radiation
126
which condition is linked to infared and what does it look like
erythema ab igne
reticulated erythema, hyperpigmentation, scaling and telangiectasia
-pattern in dermal vasculature
127
who commonly gets erythema ab igne 2
1. shins of older people who cant afford to heat their homes adequately so they huddle close to a fire
2. also can get it from laptops
128
ultraviolet radiation 3 wavelength groups
- UVA 320-400
- UVB- 290-320
- UVC <290
129
what is UVC
UVC does not penetrate the atmosphere
130
what wavelength is visible light
>400
131
what is the erythema action spectrum
- ability of radiation at any wavelength to induce erythema
- higher in UVB than UVA
- even taking into consideration that UVA has a higher spectral output
- most of the erythemal activity of the sunshine comes from UVB 80%
132
what is larger UVA or UVB- spectral output
most radiation comes from UVA
133
when and where is UVR higher
- UVR peaks at midday for both UVA and UVB
- close to the equator UVR is compressed into a shorter day - so avoid midday!
- as the sun lowers in the sky -radiation from a fixed solar angle is distributed over a larger area - this reduces wavelengths especially those <320 the main sunburn wavelenths
- clouds attenuate UV due to scattering and also infared- but they attenuate infared more than UV- hence temperature is a bad proxy for UVR as can underestimate amount of UVR
- UVR passes through water
- snow reflects up to 90% of UVR
- annual exposure- annual UVR rises on where people holiday...
- lifestyle eg gamer vs athlete
134
what is a monochromator used for
solar urticaria to test erythema response to UV
135
what is sunburn
dilatation of the vasculature in response to damage from UV radiation
- tends to peak between 8 and 24 hours and disappears a few days later
- can use laser doppler to detect it before 8 hours
136
what drug can inhibit suburn erythema
indomethacin- cyclooxygenase inhibitor
| -inhibitor production of NO- reduce vasodilation
137
what is xeroderma pigmentosa
- abnormal freckling
- abnormal response to UV light -develop more erythema with trivial amounts of UV exposure and it is prolonged erythema
- autosomal recessive disorder
- rare
- develop skin cancers
- inability to repair DNA damage due to UV radiation exposure - mutations and skin cancer
138
why do people develop skin cancers
- whilst there is DNA damage repair from UV radiation
- even in normal people not all the damage is completely repaired and the accumulations of the damage over time results in accumulation of multiple mutations which lead to skin cancers
139
mode of inheritance of xeroderma pigmentosa
autosomal recessive
140
number of skin cancers patients with xeroderma pigmentosum develop varies why
1. XP is heterogenous and different genes contribute to DNA repair so severity varies depending on which gene is mutated
2. difference in skin exposure eg living in Africa vs living in Scotland
3. skin type- dark skin type melanin protects more
141
what do freckles represent
focal overproduction of melanin in the skin
- number of melanocytes are the same
- good at photoprotection
- related to gene and environment
142
constitutive pigmentation vs facultative pigmentation
constitutive pigmentation= baseline
facultative pigmentation= tanning - increase from baseline pigmentation as a response of UV radiation on melanin production
143
how does melanin protect against UVR
- melanocytes are not uniformly distributed in skin- they are focused in the basal layer
- melanosomes cluster around the nucleus on top of it to protect the DNA in the nucleus against UVR- melanin cap
- melanin absorbs visible light and some UVR
144
what controls the production of melanin
range of enzymes including tyrosinase
145
eumelanin are
black/ brown
146
pheomelanin
are red/ yellow
147
control of melanin ratio is under
melanocortin 1 receptor
| -mutations of this gene cause red hair so get a high pheomelanin to eumelanin
148
skin type 1
pale skin
red/ blonde hair and light eyes
rarely if ever tans, always burns
149
skin type 2
beige
darkish blonde/ lightbrown
occasionally tans, usually burns
150
skin type 3 olive
brown hair, brown eyes
| usually tans, sometimes burns
151
skin type 4
medium brown
dark hair , brown eyes
easily tans, burns minimally
152
skin type 5
dark
dark brown, black hair
always tans, rarely burns
153
skin type 6
always tans, never burns
| deep dark colour
154
ways in which the skin responds to UVR
- tanning- facultative pigmentation although is less effective
- stratum corneum thickens in response to UVR so it blocks more photons
155
use of phototherapy
psoriasis
| eczema
156
what is vitiligo
autoimmune
| melanocytes are destroyed in discrete areas -white patches
157
albinism pathophysiology
melanocytes are present but dont synthesise normal amounts of melanin
158
commonest cancer uk
skin cancer 20%
159
% of eczema
15%
160
% psorisais
2%
161
moderate or severe acne %
20%
162
main causes of skin disease death are
skin cancers
blistering eg pemphigoid and pemphigus
cutaneous adverse drugs- toxic epidermal necrolysis
163
what are infectious skin diseases
```
viral warts
impetigo
herpes simplex- lips
herpes zoster- shingles
-candida
-ringworm
-staph
-scabies
```
164
haematuria and purpuric rash suggests
glomerulonephritis
