Intro to Dermatology Flashcards
What are the two major embryological elements of the skin?
- Epidermis- originates from ectoderm
2. Dermis- arises from mesoderm that comes into contact with inner surface of epidermis
What is the mesoderm essential for?
-for inducing differentiation of epidermal structure e.f hair follicles
What is the development of the skin stages?
- epidermis forms by week 4- single basal layer of cuboidal cells
- secondary layer of squamous, non-keratinising cuboidal cells (periderm) develops in week 5& generates white, waxy protective substance- vernix caseosa
- from week 11, basal layer of cuboidal cells (stratum germinative) proliferates to form multilayered intermediate zone - four more superficial strata Spinosum(spinous),granulosum(granular),lucidum(clear;foundon palms of hands and soles of feet), and corneum (horny).
- Epidermal ridges protrude as troughs into developing dermis beneath neurovascular supply develops into dermal papillae
- Weeks9-13developmentofhairfolliclesinstratumgerminativum and appearance of lanugo hair
What happens to melanocytes during skin development?
- derived from neural crest
- make melanoblasts
- migrate dorsally between week 6-8 to developing epidermis (dermis) and hair follicles
- by week 12-13, most melanoblasts have reached destination and differentiated into melanocytes
- subset of melanoblasts from melanocyte stem cells in hair follicle bulge that replenish differentiated melanocytes
What is the regulation of melanocytes?
- Melanocortin 1 receptor (MC1R), a G protein-coupled receptor regulates quantity and quality of melanins produced:
- Agonists α-melanocyte-stimulating hormone (αMSH) & adrenocorticotropic hormone (ACTH) → activation of MC1R by agonist → melanogenic cascade → synthesis of eumelanin
- Agouti signaling protein (ASP) reverses those effects & elicit production of
- ACTH can also up-regulate expression of MC1R gene - Exposure to UV
- increased expression of transcription factor MITF & downstream melanogenic proteins, including Pmel17, MART-1, TYR, TRP1, and DCT → increases in melanin content
- Increased PAR2 in keratinocytes → increases uptake & distribution of melanosomes by keratinocytes
What are the main the structures of the skin?
- epidermis
- basement membrane/ dermal-epidermal junction
- dermis: connective tissue
- subcutaneous fat
What is the structure of the epidermis?
- composed of keratinocytes
- division of cells in basal layer
- progressive differentiation/ flattening; Stratum spinosum, Stratum granulosum, Stratum lucidum (palms and soles only), Stratum corneum (no nuclei or organelles)
- cellular progression from basal layer to surface in 30 days- accelerated in skin diseases (e.g psoriasis)
What does the filamentous cytoskeleton of keratinocytes comprise of?
- actin-containing microfilaments
- tubulin-containg microtubules
- intermediate filaments (keratins)
What are the roles of keratins?
- structural properties
- cell signalling
- stress response
- apoptosis
- wound healing
What are desmosomes?
- major adhesion complex in epidermis
- anchor keratin intermediate filaments to cell membrane and bridge adjacent keratinocytes
- allow cells to withstand trauma
What are gap junction and why are they needed?
- clusters of intercellular channels (connexons)
- directly form connections between cytoplasm of adjacent keratinocytes
-essential for cell synchronisation, cell differentiation, cell growth and metabolic coordination
What are adherents junctions?
- transmembrane structures
- engage with actin skeleton
What are tight junctions?
-role in barrier integrity and cell polarity
What are melanocytes?
- dendritic
- distribute melanin pigment (in melanosomes) to keratinocytes
What are Langerhans cells?
- dendritic
- antigen-presenting cells
What are merkel cells?
-mechanosensory receptors
What are the cells in the epidermis?
-melanocytes
-langerhans cells
merkel cells
mast cells
What is the basement membrane and what are its roles?
-dermal-epidermal junction
-proteins and glycoproteins:
collagens (IV, VII), laminin, integrins
Roles:
- cell adhesion
- cell migration
What is the structure of the dermis?
- Papillary dermis:
- superficial
- loose connective tissue
- vascular - Reticular dermis:
- deep
- dense connective tissue
- forms bulk of dermis
Proteins
- collagen- TI and TIII
- elastic fibres-fibrillin, elastin
Glycoproteins
-fibronectin, fibula, intregrins, which all facilitate cell adhesion and cell motility
Ground substance
-between dermal collagen and elastic tissue- glycosaminoglycan/ proteoglycan
What cells are present in the dermis?
- fibroblasts
- histiocytes
- mast cells
- neutrophils
- lymphocytes
- dermal dendritic cells
What is the vernix caseosa?
-generates white, waxy protective substances
What is the function of MC1R?
-regulates quantity and quality of melanins produced
Which stratum is only found in the palms and the soles?
-stratum lucid
Where are melanocytes derived from?
-the neural crest
What are the most predominant cells in the dermis?
-fibroblasts
What forms the superficial component of the dermis?
-the papillary dermis
What is the blood supply for the skin?
- deep and superficial vascular plexus
- blood supply does for cross into epidermis
What is the sensory innervation in the skin to?
- free nerve endings
- hair follicles
- expanded tips
What is the autonomic innervation in the skin to?
Cholinergic- eccrine
Adrenergic- eccrine and apocrine
What is the Pilosebaceous unit?
-hair follicles
-consists of the hair shaft, the hair follicle, the sebaceous gland, and the erector pili muscle
What are the afferent nerves in the skin?
- Corspuscular
- encapsulated receptors e.g dermis- Pacinian, Messiners - Free
- non-encapsulated receptors e.g epidermis- Merkel cells
What are Meissner’s corpuscles?
- aka tactile corpuscle
- encapsulated, unmyelinated mechanoreceptors
- light touch and slow vibration
- sense low-frequency stimulation at level of dermal papilla
- most concentrated in thick hairless skin- finger pads and lips
What are Ruffini corpuscles?
- slow acting mechanoreceptor
- sensitive to skin stretch
- deeper in dermis
- spindle-shaped
- highest density round fingernails - monitors slippage of objects
What are the Pacinian corpuscles?
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
Modified epidermal cells:
- stratum basale, directly above basement membrane
- most populous in fingertips
- also in palms, soles, oral and genital mucosa
Where are Meissner’s corpuscles most concentrated?
-in thick hairless skin (finger pads and lips)
Which epidermal nerve receptors are responsive to light touch and what are the fibres?
- Meissner
- Merkel
- Free
AB
Which epidermal nerve receptors are responsive to touch, pressure and what are the fibres?
- Merkel
- Ruffini
- Pacinian
- Free
AB, AD(delta)
Which epidermal nerve receptors are responsive to vibration and what are the fibres?
- Meissner
- Pacinian
AB
Which epidermal nerve receptors are responsive to temperature and what are the fibres?
-Thermoreceptors
AD(delta)
C
Which epidermal nerve receptors are responsive to pain and what are the fibres?
-Nociceptor (free nerve endings)
AD(delta)
C
Which main bacteria make up the skin micro biome?
Actinobacteria:
- propionibacteria
- corynebacteria
Firmicutes
- clostridia
- bacilli (Staphylococcus)
Bacteroidetes
Proteobacteria
What are the 6 functions of the skin?
- immunological barrier
- physical barrier
- thermoregulation
- sensation
- metabolic function
- aesthetic appearance
What role do Langerhans cells play in the immune barrier of the skin?
- sentinel cells in epidermis
- innate immune response against microbial threats
- contribute to immune tolerance
- form dense network with which potential invaders must interact
- specialised at “sensing” environment
- extend dendritic processes through intercellular tight junction to sample outermost layers of the skin (stratum corneum)
- interpret microenvironmental context to determine appropriate quality of immune response
- in absence of danger, promote expansion and activation of skin-resident regulatory cells - Tregs
- when sense danger (PAMP), rapid initiation of innate antimicrobial responses
- induction of adaptive response- power and specificity of T-cell
What do Langerhans cells do in absence of danger?
-promote expansion and activation of skin-resident regulatory cells - Tregs
What are Tregs?
-skin-resident regulatory cells
What do Langerhans cells do when they sense danger?
-rapid initiation of innate antimicrobial response
What are PAMPs?
-pathogen-associated molecular patterns
Where in the skin are the Langerhans cells found?
-epidermis
Which cells carry out immune surveillance in the dermis?-
- tissue-resident T-cells
- macrophages
- dendritic cells
-rapid, effective immunological backup if epidermis breached
What are the endogenous antibiotics in the skin?
Keratinocyte-derived endogenous antibiotics:
- defensins
- cathelicidins
-innate immune defence against bacteria, viruses and fungi
What are the physical barrier function of the skin?
- cornified cell envelope and stratum corneum restrict water and protein loss from skin
- extensive inflammatory skin disease leading to erythroderma can cause high-output heart failure and renal failure due to transepidermal fluid loss
- subcutaneous fat has important roles in cushioning trauma
- UV barrier
- melanin in basal keratinocytes- protection against IV-induced DNA damage
How does the skin carry out thermoregulation?
- vasodilation or vasoconstriction in deep or superficial vascular plexuses to regulate heat loss
- eccrine sweat glands for cooling effect
- role in fluid balance
What are the metabolic functions of the skin?
- vitamin D synthesis
- subcutanenous fat
- calorie reserve
- skin contains 80% of total body fat (in non-obese individuals)
- hormone leptin release from subcutaneous fat- acts on hypothalamus- regulates hunger and energy metabolism
How does vitamin D synthesis occur in the skin?
- UVB
- 7-dehydrocholesterol to pre-vitamin D3 to 1,25(OH)2D3
What is the aesthetic appearance of skin important to understand?
- psychosexual function
- increased risk of suicide
What are the roles of the subcutaneous fat?
- calorific reserve
- insulation
- cushioning from trauma
- major source of leptin (suppresses appetite)
What are the functions of the hair?
- protection against external factors
- sebum
- apocrine sweat
- thermoregulation
- social and sexual interaction
- epithelial and melanocyte stem cells
Where are terminal hairs found?
-scalp, eyebrows, eyelashes
What type of hair is on the rest of the body?
-vellus hairs
What is the hair cycle?
- Anagen - where new hair forms and grows
- 85% of hair
- lasts 2-6 years - Catagen -regressing phase
- 1% of hair
- lasts 3 weeks - Telogen - resting phase
- 10-15% of hair
- lasts 3 months
-then loss of old hair
What is the infundibulum in regards to the structure of hair?
- uppermost portion of hair follicle
- from opening of sebaceous gland to surface of skin
What is the isthmus in regards to the structure of hair?
-lower portion of the hair follicle between opening of sebaceous gland and insertion of arrestor pili muscle
What is trichilemmal keratinisation?
-when epithelium keratinisation begins with lack of granular layer
What is the bulge in regards to the structure of hair?
- segment of outer root sheath located at insertion of arrector pili muscle
- lower most portion of hair follicle, includes follicular dermal papilla and hair matrix
- hair follicle stem cells reside here
What roles do the hair follicle stem cells have?
- hair follicle stem cells migrate downwards
- generate anlagen hair follicle
- enter hair bulb matrix
- proliferate and undergo terminal differentiation to form hair shaft and inner root sheath
- upwards (distally) to form sebaceous glands and to proliferate in response to wounding.
What is the purpose of the outer root sheath (ORS) ?
- extends along from hair bulb to infundibulum and epidermis
- serves as a reservoir of stem cells
What is the purpose of the inner root sheath (ORS) ?
- guides/shapes hair
- encloses follicular dermal papilla, mucopolysaccharide-rich strome, nerve fibre & capillary loop
What are the 5 functions of the nails?
- -protection of underlying distal phalanx
- counterpressure effect to pulp important for walking and tactile sensation
- increase dexterity/ manipulation of small objects
- enhance sensory discrimination
- facilitate scratching or grooming
What is the nail plate?
- final product of proliferation and differentiation of nail matrix keratinocytes
- emerges from proximal nail fold
- grows at 1-3mm/month
- firmly attached to nail bed
- lined laterally by lateral nail folds
What is the nail matrix?
- produces the nail plate
- lies under proximal nail fold, above bone of distal phalanx (to which it is connected by a tendon)
- lunula only visible proportion
- nail matrix keratinocytes differentiate- lose their nuclei and are strictly adherent- cytoplasm completely filled by hard keratins
- also contains melanocytes
What is psoriasis?
- chronic, immune-mediated disorder
- polygenic predispositions combined with environmental triggers
- sharply demarcated, scaly, erythematous plaques characterise most common form of psoriasis
- common sites of involvement are scalp, elbows, knees, nails hand, feet, trunk, intergluteal fold
What are the possible environmental triggers for psoriasis?
- trauma
- infections
- medications
What is the pathophysiology of psoriasis?
- -stressed keratinocytes release DNA/RNA
- form complex with antimicrobial peptides
- induce cytokine (TNFa, IL-1 and IFN-a) 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 the clinical features of psoriasis?
- scaly erythematous plaques in extensor distribution
- genital psoriasis
- flexural psoriasis
- palmoplantar psoriasis
- subungal hyperkeratosis
- salmon pink patches- Onycholysis
- pitting
- eryhtroderma
- guttate psoriasis
What is the management of psoriasis?
Therapeutic ladder
- Topical therapies:
- vitamin D analogues
- topical corticosteroids
- retinoids
- topical tacrolimus/ pimecrolimus - Phototherapy:
- narrowband UVB
- PUVA (psoralen + UVA) - Retinoids (hand dermatitis)
- Systemic immunosuppression:
- methotrexate
- ciclosporin
- fumaric acid esters
- apremilast - Advanced therapies:
- biologics (anti-TNF, anti-IL17, anti-IL23)
- JAK inhibitors
What is atopic eczema?
- intensely pruritic chronic inflammatory condition
- complex genetic disease with environmental influences
- typically begins during infancy or early childhood
- often associated with other ‘atopic’ disorder e.g asthma, rhinoconjunctivitis
- acute inflammation of cheeks, scalp and extensors in infants
- flexural inflammation and lichenification in children and adults
- daily emollients and anti-inflammatory therapy are cornerstone of management
- eczema (dermatitis)- umbrella term: atopic eczema, seborrhoea dermatitis, venous stasis eczema, allergic contact dermatitis, irritant contact dermatitis
What is the pathophysiology of eczema?
Barrier defect:
- reduced extracellular lipids and impaired ceramide production
- increased transepidermal water loss (TEWL)
- impaired protection against microbes and environmental allergens
Immune dysregulation:
- staphylococcal superantigens stimulate Th2 lymphocyte responses and subvert T-regg
- T-cell infiltrate- bias towards Th2 response
- role of micro biome ?
- eosinophils
What is the function of filaggrins?
-binds and aggregate certain bundles and intermediate filaments to form cellular
What are the clinical features of atopic eczema?
-infantile phase atopic dermatitis: erythematous, oedematous papule & plaques +- vesiculation
- lichenification, crusting and excoriation and dyspigmentation postinflammatorydyspigmentation pigmentation
- flexural dermatitis causing hypo pigmentation
- flexural dermatitis
- fissuring
- allergic contact dermatitis
- impetiginisation
- gold crust
- staphylococcus aureus
- venous stasis eczema
- eczema herpeticum
- patients with atopic eczema are predisposed towards HSV infection that can spread rapidly, involve internal organs and be fatal
What is the management of atopic eczema?
Lifestyle:
- emollients
- omission of soap
Clinical Nurse Specilaist involvement:
- topical application technique
- day treatment
- habit reversal
- co-morbidites
- patch-testing
- biopsy (e.g resistant nipple eczema should undergo biopsy to exclude Paget’s disease of the nipple)
Therapeutic ladder:
- Topical therapies:
- topical corticosteroids- correct potency for correct site
- retinoids (hand dermatitis)
- topical tacrolimus/pimecrolimus - Phototherapy:
- narrowband UVB
- PUVA (hand dermatitis)
-retinoids (hand dermatitis)
Systemic immunosuppression:
- methotrexate
- ciclosporin
- azathioprine
- mycophenolate mofetil
Advanced therapies:
- biologics (anti-IL-4a, anti-IL13)
- JAK inhibitors
lecture slides
https://d3c33hcgiwev3.cloudfront.net/WDPKWv0bTE2zylr9G9xNpQ_1310a535ae8544ddabcb2fb28dbbe6a4_SV_Final_Derm_LE01Introduction_to_dermatology.pdf?Expires=1581206400&Signature=K4o82cbpgd9OPSPKzMtglQoq0SbRT4YRIV-FtbSJay5tI1Fyb9PGLde-26O8IXIU9oBl2FteAwfvSNu1gobvNQw21Puiy0rK7HIMmVKOjY1aOYpVMgcuYBFYGLd6yF-2Yf1k2uLVzKzc1YL16LoXLVGudIOjW8ZzR6Z62KXABVo&Key-Pair-Id=APKAJLTNE6QMUY6HBC5A
