dermatology Flashcards
what does the skin arise from
1) epidermis
2) dermis
what is the epidermis
it originates from ectoderm (the outermost layer of the 3 primary germ layers)
what is the dermis
it arises from the mesoderm and is beneath the epidermis
comes into contact with inner surface if epidermis
what is the mesoderm essential for
inducing differentiation of epidermal structures (eg hair follicle)
what happens by week 4
the epidermis forms as a single basal layer of cuboidal cells
what happens in week 5
a secondary layer of squamous, non-keratinising cuboidal cells called the periderm forms
this generates a white, waxy protective substance called the vernix caseosa
what happens from week 11
basal layer of cuboidal cells (stratum germinativum) proliferates to form multilayered intermediate zone > 4 more superficial strata
name the layers that arise from the stratum germinativum
stratum corneum stratum lucidum stratum granulosum stratum spinosum stratum germinativum
what happens to epidermal ridges
they protrude as troughs into the developing dermis underneath
what does the neurovascular supply develop into
dermal papillae
what happens from weeks 9-13
development of hair follicles in stratum germinativum
appearance of lanugo hair
give an overview of the structure of the skin (4 layers)
epidermis
basement membrane (dermal-epidermal junction)
dermis (connective tissue)
subcutaneous fat
what is the primary cell in the epidermis
keratinocytes
what does progressive differentiation and flattening of the cells in the basal layer give rise to and how long does it take
stratum spinosum stratum granulosum stratum lucidum (palms and soles only) stratum corneum (no nuclei or organelles) 30-42 days
what happens to the process of proliferation and flattening in psoriasis
it becomes accelerated and progressively flatter
red/scaly/itchy
what does the filamentous cytoskeleton of keratinocyte comprise of
in size order (smallest to biggest)
actin containing microfilaments (7nm)
intermediate filaments containing keratins (7-10nm)
tubulin containing microtubules (20-25nm)
what are the roles of keratin (SSWAC)
stress response structural properties wound healing apoptosis cell signalling
what are 4 features within/between keratinocytes in the epidermis
desmosomes
gap junctions
adherens junctions
tight junctions
what are desmosomes
major adhesion complex in epidermis
they anchor keratin intermediate filaments to cell membrane
they also bridge adjacent keratinocytes
allows cells to withstand trauma
what are gap junctions
clusters of intracellular channels (connexons) - form pore for gap junction
directly form connections between cytoplasm of adjacent keratinocytes
essential for cell synchronisation, cell differentiation, cell growth and metabolic coordination
what are adherens junctions
transmembrane structures
engage with the actin skeleton
what are tight junctions
they have a role in barrier integrity and cell polarity
other cells in the epidermis (4)
melanocytes
langerhan cells
merkel cells
mast cells
what are melanocytes
they are dendritic
distribute melanin pigment (in melanosomes) to keratinocytes
the number of melanocytes are equal among skin types
what are langerhan cells
dendritic
antigen presenting cells
immune cells
what are merkel cells
mechanosensory receptors (sensory of mechanical stimuli)
what is the basement membrane
dermal epidermal junction
what does the basement membrane consist of
proteins and glycoproteins - collagen (most commonly 4,7), laminin and integrins
role of the basement membrane
cell adhesion and cell migration
what is the dermis
supporting the ECM - provides resilience
and is made of two layers
the papillary dermis and the reticular dermis
what is the papillary dermis
- superficial
- loose connective tissue
- vascular
what is the reticular dermis
- deep
- dense connective tissue
- forms bulk of dermis
what is found in the dermis
proteins
glycoproteins
ground substance
what proteins are found in the dermis
collagen (80-85% of the dermis) - mainly types 1 and 3 elastic fibres (2-4%) - fibrillin and elastin
what glycoproteins are found in the dermis and what do they do
fibronectin, fibulin, integrins
facilitate cell adhesion and motility
what is ground substance in the dermis
it is between dermal collagen and elastic tissue
glycosaminoglycan and proteoglycan
what are the primary cells found in the dermis
fibroblasts
what are 5 other cells found in the dermis
histiocytes mast cells neutrophils lymphocytes dermal dendritic cells
vascular supply of the skin
blood supply - deep and vascular plexus
and does not cross into the epidermis
mostly in the papillary dermis
innervation of the skin
sensory (free nerve endings, hair follicles, expanded tips) and autonomic (cholinergic - eccrine and adrenergic - eccrine and apocrine)
Merkel cells Pacinian corpuscle Ruffini Meissner cell Noiciceptors Free nerve endings
define cholinergic
inhibits or mimics actions of NT acetylcholine
define adrenergic
working on adrenaline/noradrenaline receptors
what are eccrine glands
open directly onto the surface of the skin
involved in thermoregulation
what are apocrine glands
scent
mostly in armpits and groin
what is the pilosebaceous unit
hair shaft hair follicle sebaceous gland errector pili muscle arterioles shunts
vascular supply of the skin pt2 hehehehe
afferent nerve fibres form branching network often accompanying blood vessels to form a mesh of interlacing nerves in the superficial dermis (papillary dermis)
innervation of nerves
varies by body site
face and genitalia have most innervation
explain afferent nerves
afferent nerves > corpuscular and free
corpuscular > encapsulated receptors (dermis eg pacinian and meissners)
free > non-encapsulated receptors (epidermis eg merkel cells)
what is the ruffini corpuscle (aka bulbous corpuscle)
slow acting mechanoreceptor deeper in dermis spindle shaped sensitive to skin stretch highest density around fingernails monitors slippage of objects
what is the pacinian corpuscle (aka lamellar corpuscles)
encapsulated
rapidly adapting (phasic) mechanoreceptor
deep pressure and vibration (deep touch)
vibrational role - detects surface texture
ovoid
dermal papillae of hands and feet
what are merkel cells
non encapsulated mechanoreceptors
light/sustained touch, pressure
oval shaped
what are modified epidermal cells
in stratum basale - directly above basement membrane
most populous in fingertips
also in palms, soles, oral and genital mucosa
nerve endings and fibre for light touch
meissner
merkel
free
fibre = A beta
nerve endings and fibre for touch and pressure
merkel ruffini pacinian free fibre = A beta and A delta
nerve ending and fibre for vibration
meissner
pacinian
fibre = A beta
nerve ending and fibre for temperature
thermoreceptors
fibre = A delta, C
nerve endings and fibres for pain
nociceptor (free nerve endings)
fibre = A delta, C
what is the microbiome
microbiota = bacteria, fungi and viruses
1 million bacteria/cm2 of skin
what are the predominant bacteria on skin
actinobacteria firmicutes bacteroidetes proteobacteria the composition of each niche depends on the environment
what is the role of the microbiome
immune modulation and epithelial health
disease
functions of the skin (IPTSMA)
immunological barrier physical barrier thermoregulation sensation metabolism aesthetic appearance
langerhan cells in the epidermis
dendritic cells
macrophage family
sentinel cells in epidermis
initiate immune response against microbial threats
contribute to immune tolerance
form dense network with which potential invaders must interact
how do langerhan cells work
specialised at sensing environment
extend dendritic processes through intercellular tight junctions to sample outermost layers of skin - stratum corneum
interpret microenvironmental context > determine appropriate quality of immune response
in absence of danger - promote expansion and activation of skin resident regulatory cells (T-regs)
when they sense danger (PAMP) rapid initiation of innate antimicrobial responses
induction of adaptive response - power and specificity of T cell
how does the skin function as an immune barrier (dermis)
immune surveillance is also carried out in the dermis by
tissue resident T cells
macrophages
dendritic cells
rapid effective immunological backup if epidermis is breached
how are keratinocytes involved in immune defence
keratinocyte derived endogenous antibiotics (defensins and cathelicidins) provide innate defence against bacteria, viruses and fungi
what can cathelicidin do
modulate cell differentiation
it is a microbicidal
modulates PRR (pattern recognition receptor) signalling
induce chemokines
chemotactic (movement due to chemical stimulus)
modulate cell function
modulate cell death
angiogenic (formation of new blood vessels)
cell proliferation
describe the skin as a physical barrier
against external environment
cornified cell envelope and stratum corneum restrict water and protein loss from skin
- high output cardiac failure and renal failure in extensive skin disease
subcutaneous fat has important in cushioning trauma
UV barrier
melanin in basal keratinocytes - protection against UV - induced DNA damage-
how does the skin deal with thermoregulation
vasoconstriction and vasodilation in deep or superficial vascular plexuses > regulate heat loss
eccrine sweat glands > cooling evaporating effect
role in fluid balance
metabolic functions of the skin
vitamin D synthesis (regulates Ca2+ and PO43-)
subcutaneous fat > under skin
- calorie reserve
- 80% of total body fat in non obese individuals
- hormone leptin release - acts on hypothalamus > regulates hunger and energy metabolism
the skin and its aesthetic appearance
psychosexual function
increased risk of suicide
what are the functions of the hair
protection against external factors sebum apocrine sweat thermoregulation social and sexual interaction epithelial and melanocyte stem cells terminal hairs (thicker, longer and darker) - scalp, eyebrows and eyelashes the rest of the body has vellus hairs (except palms. soles, mucosal regions of lips and external genitalia)
what are the 3 components of the hair cycle
1) anagen
2) catagen
3) telogen
4) loss of old hair
describe anagen
where new hair forms and grows
85% of hair lasts 2-6 years
describe catagen
regressing phase
1% of hair - lasts 3 weeks
describe telogen
resting phase
10-15% of hair - lasts 3 months
what does the pilosebaceous unit contain
hair shaft
hair follicle
sebaceous gland
arrector pili muscle
STEPS for formation of pilosebaceous unit
pockets of epithelium are continuous with superficial epithelium
they envelop a small papilla of dermis at their base
arrector pili (smooth muscle) extends at angle between surface of dermis and point in follicle wall
holocrine (secretion is own disintegrated secretory cells and products) sebaceous glands open into the pillory canal
(in axillae - follicles are associated with apocrine glands)
what is the infundibulum
uppermost portion of the hair follicle extending from the opening of sebaceous gland to surface of the skin
what is the isthmus (not thyroid gland)
lower portion of the upper part of hair follicle between opening of sebaceous gland and insertion of arrector pili muscle
how does epithelium keratinisation begin
begins with lack of granular layer named trichilemmal keratinisation
what is the bulge
segment of the outer root sheath located at insertion of arrector pili muscle
hair follicle stem cells reside here
they can migrate upwards or downwards
what happens when hair follicle stem cells migrate upwards (distally)
form sebaceous glands and to proliferate in response to wounding
what happens when hair follicle stem cells migrate downwards
generate new lower anagen hair follicle > enters hair bulb matrix > proliferate and undergoes terminal differentiation to form hair shaft and inner root sheath
what is the bulb
lowermost portion of the hair follicle
includes follicular dermal papilla and hair matrix
what is the outer root sheath
extends along from the hair bulb to the infundibulum and epidermis and serves as a reservoir of stem cells
what is the inner root sheath
undergoes proliferation and differentiation
guides and shapes hair
encloses dermal papilla, mucopolysaccharide rich strome, nerve fibre and capillary loop
what is the function of the nails
protection of underlying distal phalanx
counter pressure effect to pulp important for walking and tactile sensation
increase dexterity/manipulation of small objects
enhance sensory discrimination
facilitate grooming or scratching
what is the nail plate
final product of proliferation and differentiation of nail matrix keratinocytes
where does the nail plate emerge from
proximal nail fold
how much does the nail plate grow each month
1-3 mm
what is the nail plate firmly attached to
nail bed
what does the nail plate detach at
hyponychium
what is the nail plate lined laterally by
lateral nail folds
what is the nail matrix
produces nail plate
nail matrix keratinocytes grow outwards and differentiate > lose their nuclei and are strictly adherent - cytoplasm is completely filled by hard keratins
also contains melanocytes - when injured = pigment
hard nuclear without other organelles
where does the nail matrix lie
under proximal nail fold, above the bone of distal phalanx (to which it is connected by a tendon)
what is the only visible portion of the nail matrix
lunula
what is psioriasis
chronic, immune mediated disorder (long term inflammatory)
a skin disease that causes red, itchy scaly patches, most commonly on the knees, elbows, trunk and scalp
what are the causes of psoriasis
polygenic predisposition combined with environmental triggers eg trauma, infections or medications
what is the most common form of psoriasis and common sites
sharply dermarcated, scaly, erythematous plaques
scalp, elbow, knees, nails, hands, feet and trunk (including intergluteal fold)
what is the most common systemic manifestation of psoriasis
psoriatic arthritis
what is the pathophysiology of psoriasis
keratinocytes undergo stress > release DNA/RNA > form complex with antimicrobial peptides (endogenous antibodies) > induce cytokines (TNF-alpha, IL-1 and IFN-alpha) production > activate dermal dendritic cells (dDCs)
dDCs migrate to lymph nodes > promote Th1, Th17, Th22 cells > chemokine release - migration of inflammatory cells into dermis > cytokine release > keratinocyte proliferation > psoriatic plaque
what are flectures
skin to skin areas due to friction is not scaly
what is nail pitting (feature of psoriasis)
indents in nail
what is erythrodermic psoriasis
90%+ of your body = red
what is guttate psoriasis
spores
how to manage psoriasis (lifestyle)
alcohol
smoking
cormorbidities
therapeutic ladder
topical therapies for psoriasis
vitamin D analogues
topical corticosteroids (reduce inflammation)
retinoids (vitamin A - immunity and skin health)
topical tacrolimus/pimecrolimus
phototherapy as a treatment for psoriasis
narrowband UVB
PUVA (psoralen + UVA)
acitretin (vit A analogue tablets > keratin differentiation process > does not proliferate wrong)
systemic immunosuppression methotrexate ciclosporin
advanced therapies PDE4 inhibitors (apremilast) biologics (anti-TNF alpha, anti IL-17, anti-IL23) JAK inhibitors
what is atopic eczema
has to be itchy
intensely pruritic chronic inflmammatory condition
conplex genetic disease with environmental influences
typically begins during infancy/childhood
and is often associated with other atopic disorders eg. asthma, rhinoconjunctivitis
features of atopic eczema
acute inflammation of cheeks, scalp and extensors in infants
flexural inflammation and lichenification in children and adults
what is eczema dermatitis
umbrella term for
atopic eczema, seborrheic dermatitis (dandruff), venous stasis eczema, allergic contact dermatitis, irritant contact dermatitis
pathophysiology for atopic eczema (not full version bc it’s too long and im tired)
barrier defect : filaggrin binds and aggregates keratin filaments and intermediate filaments to form cellular scaffold in corneocytes (in stratum corneum)
immune dysregulation Th2 lymphocytes stimulated and subversion of T-reg, T cell infiltrate
clincal features of atopic eczema
exaggeration of skin
lichenification, crusting and excoriation and dyspigmentation, post inflammatory dyspigmentation, flexural dermatitis causing hypopigmentation
fissuring - vertical cracks in skin
infantile phase atopic dermatitis = erythematous, oedematous papule and plaques and or not vesiculation (tiny blisters or erosions)
allergic contact dermatitis
allergic contact dermatitis
posion ivy - bubbly
nickel - small red bumps
shoes - potassium chromate - weird butterfly shape
impetiginisation
- gold crust, staphylococcus aureus
venous stasis eczema
purple shade
eczema herpeticum
- on face - emergency, HSV, dark spots/scars
lifestyle management for atopic eczema
emollient
omission of soap
management - clinical nurse specialist involvement
topical application technique
day treatment
habit reversal
other managements for atopic eczema
comordities patch testing biopsy therapeutic ladder topical therapies
when should you always take a biopsy
nipple eczema because it could be Pagets or cutaneous lymphoma
what are topical therapies
topical corticosteroids - correct potency for correct site topical tacrolimus/pimecrolimus underuse = poor adherence overuse = tachyphylaxis/adverse effects FTU - fingertip unit
what is phototherapy
narrowband UVB
PUVA - hand dermatitis
what is the steroid ladder and list in potency
underuse - poor adherence overuse - tachyphylaxis/adverse effects correct steroid for correct site FTU least potent to most: hydrocortisone clobetasone (eumovate) betamethasone (betnovate) mometasone (elocon) clobetasol (dermovate)
adverse effects of topical corticosteroids
rare = skin atrophy, folliculitis, exacerbation of acne and rosacea, infection
very rare = perioral dermatitis (right), rebound syndrome (tachyphylaxis), allergy (to steroid itself or vehicle)
extremely rare = hormonal imbalance (suppression of hypothalamic pituitary adrenal axis), hirsutism
what are adverse effects of topical calcinuerin inhibitors
burning sensation
eczema management
retinoids (hand dermatitis) systemic immunosuppression: - methotrexate - ciclosporin - azathioprine - myocophenolate mofetil advanced therapies - biologics (anti IL4 alpha, anti IL-13) - JAK inhibitors
