Week 6- Intro to Dermatology Flashcards
What 2 major elements does skin contain?
Epidermis
Dermis
What does the epidermis originate from?
The ectoderm
What does the dermis originate from?
From the mesoderm that comes into contact with the inner surface of the epidermis
What is the role of the mesoderm in skin?
It induces differentiation of epidermal structures
Describe the process of development of the skin
Epidermis forms by week 4 (single layer of cuboidal cells)
Secondary layer develops by week 5
By week 11 basal layer proliferates to form multilayered intermediate zone
Week 9-13 hair follicles develop
What are the 4 main cell types in the basal layer of skin?
Spinosum (spinous)
Granulosum (granular)
Lucidum (clear)
Corneum (horny)
What are skin stem cells called?
Melanocytes
Where are melanocytes derived from?
The neural crest
When do melanocytes migrate to the epidermis?
Week 6-8
Where do melanoblasts differentiate to melanocytes to replenish the stem cell supply?
Hair follicles
What receptor is involved with regulation of melanocytes? What type of receptor is it
Melanocortin 1 receptor (MC1R), a G protein coupled receptor
What agonists activate MC1R?
Alpha melanocyte stimulating hormone (aMSH) and adrenocorticotrophic hormone (ACTH)
What happens when MC1R is stimulated?
Melanogenic cascade is activated, eumelanin is synthesised
How is the synthesis of eumelanin prevented?
Agouti signaling protein (ASP) elicits production of pheomelanin
What upregulates the expression of the MC1R gene?
ACTH
How does UV lead to increased production of melanin?
Increases transcription factor MITF and downstream melanogenic proteins
Increases PAR2 in keratinocytes increasing uptake and distribution of melanosomes by keratinocytes
What do the epidermis and dermis contain?
Epidermis: basement membrane
Dermis: connective tissue and subcutaneous fat
What cell type is the epidermis composed of?
Keratinocytes
What strata of the basal layer is only present in the palms and soles?
Stratum lucindum
What strata of the basal layer has no nuclei or organelles?
Stratum corneum
What are some roles of keratins?
Apoptosis
Stress response
Wound healing
Cell signaling
Where are desmosomes found?
The epidermis
What do desmosomes do?
They are adhesion complexes, they anchor keratin to cell membranes and bridge adjacent keratinocytes allowing cells to withstand trauma
What is the role of melanocytes in the epidermis?
Distribute melanin pigment to keratinocytes
What is the role of Langerhans cells in the epidermis?
They are antigen presenting cells
What is the role of Merkel cells in the epidermis?
They are mechanosensory receptors
What other name is the basement membrane known as?
Dermal epidermal junction
What are some roles of the basement membrane?
Cell adhesion and cell migration
What is the role of the dermis?
Supports the ECM and provides resilience
What are the 2 main layers of the dermis?
Papillary (superficial, comprised of loose tissue) and reticular (composed of deep dense connective tissue)
What is the dermis made up of?
Proteins (collagen and elastic fibres)
Glycoproteins
Ground substance (glycosaminoglycan and proteoglycan)
What is the primary cell type of the dermis?
Fibroblasts
How abundant is collagen in the dermis?
80-85% with type I and II being most abundant
How is blood supplied to the skin?
Via deep and superficial vascular plexuses (do not cross into epidermis)
How is skin innervated?
Sensory
Autonomic: cholinergic and adrenergic
What nerve fibres innervate skin?
Afferent fibres
What are the 2 types of afferent nerves?
Corpuscular- have encapsulated receptors
Free- have non encapsulated receptors
What are Meissner’s corpuscles?
Encapsulated and unmyelinated mechanoreceptors that sense low level frequency at dermal papilla eg light touch
Where are Meissner’s corpuscles most concentrated?
Thick and hairless skin (finger pads and lips)
What are Ruffini corpuscles?
Slow acting mechanoreceptors sensitive to skin strech
Where are Ruffini corpuscules found?
Deeper in the dermis, highest density around fingernails
What are Pacinian corpuscules?
Encapsulated, rapidly adapting mechanoreceptors that assist with deep pressure and vibration
Where are Pacinian corpuscles found?
Dermal papillae of hands and feet
What are Merkel cells?
Non encapsulated mechanoreceptors for light/sustained touch and pressure found directly above the basement membrane
Where are Merkel cells most abundant?
Fingertips as well as palms and soles
What nerve endings are for light touch and what fibre is associated with light touch?
Meissner, merkel and free
Abeta fibres
What nerve endings are for touch/pressure and what fibre is associated with touch/pressure?
Merkel, ruffini, pacinian, free
Abeta and Adelta fibres
What nerve endings are for vibration and what fibre is associated with vibration?
Meissner, pacinian
Abeta fibre
What nerve endings are for temperature and what fibre is associated with temperature?
Thermoreceptor
Adelta and C fibres
What nerve endings are for pain and what fibre is associated with pain?
Nociceptor
Adelta and C fibres
Around how many bacteria are found on a cm^2 of skin?
1 million
What are the main organisms found in the skin microbiome?
Actinobacteria, firmicutes, bacteroidetes, proteobacteria
What are some functions of skin?
Immunological barrier, physical barrier, thermoregulation, sensation
What cells are involved with helping the skin be an immunological barrier and how?
Langerhans cells, they initiate immune response against microbial threats and contribute to immune tolerance
What are immunological responses of Langerhans cells in the presence and absence of danger?
Absence: promote expansion of skin regulatory T cells (Tregs)
Presence: rapid initiation of innate antimicrobial responses (PAMP)
Where are antibiotics in the skin derived from? Give examples
Derived from keratinocytes
Defensins and cathelicidins are the 2 main ones
What substance in the skin protects against UV?
Melanin in basal keratinocytes
What restricts water and protein loss from skin?
Stratum corneum and the cornified cell envelope
How does the skin carry out thermoregulation?
Via vasoconstriction and vasodilation in vascular plexuses
What glands in the skin have cooling effects?
Eccrine sweat glands
How much of total body fat is part of the skin?
80%
What hormone released from the skin regulates hunger and energy metabolism? Where specifically is it released from?
Leptin, released from subcutaneous fat
What are some functions of hair?
Protection against external factors
Thermoregulation
Apocrine sweat
What are the 2 types of hair and where are they found?
Terminal- scalp, eyebrows and eyelashes
Vellus- rest of body
Describe the 3 stages of the hair cycle and how long they last
Anagen- new hair forms and grows (2-6 years)
Catagen- regressing phase (3 weeks)
Telogen- resting phase (3 months)
Then loss of old hair
What are hair follicles known as?
Pilosebaceous unit
What follicle and glands does human skin contain?
Pilosebaceous follicles
Sweat glands
What is the name of the muscle that extends at an angle between the surface of the dermis and the follicle wall?
Arrector pili
What glands open into the pilary canal and are associated with apocrine glands?
Holocrine sebaceous glands
What are the 2 main parts of hair
Infundibulum- uppermost part of the follicle from opening of sebaceous gland to surface of skin
Isthmus- lower part between opening of sebaceous gland and insertion if arrector pili muscle
Where are hair follicle stem cells found?
In the bulge which is located at the insertion of the arrector pili muscle
What acts as a reserve of stem cells in hair?
The outer root sheath
What is the function of the inner root sheath in hair?
Guides and shapes hair, has a nerve fiber and capillary loop
What are some functions of nails?
Protect the underlying distal phalanx
Increase dexterity
Facilitate scratching and grooming
Counter pressure effect on pulp- important for walking and tactile sensation
What is the main part of the nail called?
The nail plate
What does the nail plate arise from?
The nail matrix
What is the nail matrix connected to and how?
Connected to the distal phalanx by a tendon
What is the only visible part of the nail matrix?
Lunula
What is the name of the structure where the nail detaches?
Hyponychium
What are the nails lined by?
By the lateral nail folds
What cells is the nail made up of? How do they develop to become nail cells?
Nail matrix keratinocytes which become denucleated and completely fill with keratin
What type of disorder is psoriasis?
A chronic, immune mediated disorder
What is the most common manifestation of psoriasis?
Sharply demarcated, scaly, erythematosus plaques
What is the most common systemic manifestation of psoriasis?
Psoriatic arthritis
How does psoriasis arise?
Due to polygenic predisposition but also affected by environmental triggers
What cell types are involved with the pathophysiology of psoriasis?
T cells
Cells involved with innate immunity
Dendritic cells
Keratinocytes
What are common sites of involvement in psoriasis?
Scalp Elbows Knees Nails Hands Feet Trunk (intergluteal fold)
Describe the pathophysiology of psoriasis
Stressed keratinocytes release DNA/RNA
They form complexes with antimicrobial peptides
Induces cytokine production
Dermal dendritic cells (dDCs) are activated
dDCs migrate to lymph nodes
Promote Th 1/17/22
Chemokines are released
Inflammatory cells are migrate to the dermis
Release of cytokines
Keratinocytes proliferate
Psoriatic plaque forms
What cytokines are induced to activate dermal dendritic cells
TNF alpha
IL-1
IFN alpha
Why do psoriatic plaques arise?
Due to keratinocyte proliferation
What are some clinical features of psoriasis?
Scaly erythematosus plaques in extensor distribution
Genital psoriasis
Flexural psoriasis
Palmoplantar psoriasis
Subungal hyperkeratosis (keratin builds up underneath nails)
Onchylosis (salmon pink patches on nails)
Pitting (of nails)
What is subungal hyperkeratosis?
Excess keratin underneath the nail bed
What is onchylosis?
Salmon pink patches on the nail
What is pitting?
Small indentations on the nail
What is erythroderma?
Widespread reddening of the skin associated with inflammation, can be accompanied by exfoliation
What is guttate psoriasis?
Small red scaly tear drop shaped spots that show up all over the skin for some psoriasis patients
What 3 main doctors are involved with managing psoriasis and what may they do?
Psychologist- help with mental health, workplace disability, personality traits, sleeping disorders
Dermatologist- skin symptoms
Rheumatologist- joint symptoms
What are some topical therapies for managing psoriasis?
Vitamin D analogues
Topical corticosteroids
Retinoids
What types of phototherapy are used to manage psoriasis?
Narrowband UVB
PUVA
What medication is given to patients with psoriasis to help manage hand dermatitis?
Retinoids
What systemic immunosupressants may be prescribed to patients with psoriasis?
Methotrexate
Ciclosporin
Fumaric acid esters
Apremilast
What is atopic eczema?
An intensely pruritic chronic inflammatory condition
What does pruritic mean?
Gives a strong urge to itch/scratch at
How does atopic eczema mainly manifest in infants?
Inflammation of cheeks, scalp and extensors
How does atopic eczema mainly manifest in children and adults?
Flexural inflammation and lichenification
How is atopic eczema treated?
Daily emollients and anti inflammatory therapy
In the pathophysiology of eczema what are the main barrier defects?
Filaggrin causes keratin bundles and intermediate filaments to form cellular scaffolds
Increased TEWL (transepidermal water loss)
Reduced extracellular lipids and impaired ceramide production
Impaired protection against microbes and environmental allergens
What is filaggrin and what does it do?
Filament aggregating protein- it forms keratin bundles and cellular scaffolds of filament
What is TEWL and how is it affected in atopic eczema?
Transepidermal water loss
In the pathophysiology of eczema what occours to cuase immune dysregulation?
There is a bias towards Th2 responses
Staphylococcal antigens stimulate Th2
Microbiome makes the eczema worse
What is fissuring in the context of eczema?
Cleavage of the skin often extending into the dermis
What is impetiginisation in the context of atopic eczema? What does it look like?
When skin lesions become infected by streptococci or staphylococci, looks like a gold crust on the skin with peeling
What is venous stasis eczema?
When due to circulation problems in the veins, blood leaks out into skin
What causes eczema herpeticum?
Herpes simplex virus
What is eczema herpeticum?
Outburst from viral infection resulting in red spots erupting on the body, must be treated as an emergency
How can lifestyle be changed to manage atopic eczema?
Use of daily emollients, omission of soap
What are some topical therapies for managing eczema?
Topical corticosteroids
Retinoids (for hand dermatitis)
What phototherapies are used for managing eczema?
Narrowband UVB
PUVA (for hand dermatitis)
What systemic immunosupressants may be prescribed for eczema?
Methotrexate
Ciclosporin
Azathioprine
Mycophenolate mofetil
What are some advanced treatments for psoriasis and atopic eczema and what do they involve?
They involve biologics
Psoriasis: JAK inhibitors, anti- TNF/IL17/IL23
Atopic eczema: JAK inhibitiors, anti-IL-4alpha/ IL13
