Dermatology Flashcards
What are the 2 major parts of the skin and where do they devolop from?
There are 2 major parts that arise from embryological elements: EPIDERMIS-originates from the ECTODERM DERMIS-arises from the MESODERM that comes into contact with inner surface of the epidermis
What is the mesoderm essential for ?
inducing differentiation of epidermal structures e.g hair follicles
Describe the stages of skin development?
1-Epidermis forms by week 4- single basal layer of CUBOIDAL cells 2-Secondary layer of squamos, non keratinising cuboidal cells(periderm) develops in week 5. This layer generatrs a white waxy protective substance 3-Week 11 onwards =basal layer of cuboidal cells(stratum germinavum) proliferates to form multilayered intermediate zone-> four more superficial strata 4-Spinosum(spinous), granulosum (granular), lucidum(only found on palms of the hand and soles of the feet) and corneum(horny) develop 5-week 10-17 Epidermal ridges protrude as troughs into developing dermis beneath neurovascular supply and develops into dermal papillae 6-weeks 9-13 developmetn of hair follicles in stratum germinativum and appearence of lanugo hair
What are melanocytes?
melanin-producing cells in the skin
Where are melanocytes derived form?
NEURAL CREST
Describe the progression of melanoblasts?
1-dervied from NEURAL CREST 2-differentiate into MELANOBLASTS 3-Migrate dorsally between week 6-8 to developing epidermis (and dermis) and hair follicles 4-By week 12-13, most melanoblast have reached destination and differentiated into melanocytes 5-Subset of meloblasts form melancyte stem cells in hair follicle bulge that replenish differentiated melanocytes
What is the difference between melanoblasts that migrate ventrially vs dorsally?
Those that migrate dorsally become melancytes Those that migrate ventrially become glial cells
Describe the regulation of melanocytes?
Regulated by MC1R (Melanocortin 1 receptor), a g-protein coupled receptior that regulates the quantity and quality of the melanins produced: -controlled by AGONISTS AND ANTAGONISTS -Agonists-alpha-melanocyte stimulating hormone (aMSH) and adrenocorticotrophic hormone(ACTH) activates the MCR1=MELANOGENIC CASCADE= synthesis of EUMELANIN(found in darker skin and hair) -Antagonist AGOUTI SIGNALLING PROTEIN (ASP) reverses these effects and elicit production of PHEOMELANIN(found in pale complexions and blonde hair) -ACTH can also upregulate(increase ) the expression of the MC1R gene
What does exposure to UV do to the skin?
-Increases expression of the transcription factor MITF and downstream melanogenic proteins including Pmel17, MART-1, YR, TRP1 and DCT=increas in melanin content -Increased PAR2 in KERATINCYTES=increases uptake and distribution of melanosomes( transport of melanin) by
What are keratincytes?
an epidermal cell which produces keratin.
What is the brief structure of the skin?
Epidermis-superficial layer(top) Basement membrane-deraml-epidermal junction Dermis: -under the epidermis -connective tissue Subcutaneous fat-below dermis
Describe the structure of the epidermis?
Composed of KERATINOCYTES predominantly Layers from bottom to to(progressive differentiation and flattening occur as you go up): -Basal Layer -Stratum spinosum -Stratum granulosm -Statum Lucidum(extra layer in palms and soles only) -Stratum corneum(no nuclei or organelles)
Where does cell division occur in the epidermis?
BASAL layer
How long does the cellular progression from the basal layer upwards take?
30 days but is accelerated in certain skin disease such as psoriasis
What does thee filamentous cytoskeleton of each keratinocyte comprise off?
-Actin containing microfilaments -Tubulin containing microtubules -Intermediate filaments containing keratin
What are the 5 roles of keratin?
-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 the different cell junction between Keratinocytes and what are there functions?
GAP JUNCTIONs: - contain cluster of intercellular channels called connexons -directly form connections between cytoplasm of adjacent keratinocytes -essential for cell synchronisation, cell differentiation, cell growth, and metabolic conditions ADHERENS junction: -Transmembrane structures -Engage with actin skeleton and hold the actin fibres together TIGHT junctions: -Play a role in barrier integrity and cell polarity
What are the other 4 cell types in the epidermis?
MELANOCYTES: -Dendritic -Distribute melanin pigament(in melanosomes) to keratinocytes LANGERHAMS: -dendritic-for immune surveillance -antigen presenting cells MARKELL CELLS: -mechanisensory receptors MAST CELLS: -role in allergic reaction
Describe the basement membrane?
-under epidermal -made of proteins and glycoproteins including collage 4 and 7, laminin and integrins
What are the 2 functions of the basement membrane ?
-Cell migration -Cell adhesion
What is the structure of the dermis?
PAPILLARY DERMIS(UPPER): -Superficial -loose connective tissue -vascular RETICULAR DERMIS: -Deep -Dense connective tissue -Forms the bulk of the dermis -less vascular supply
What is the dermis made of?
-80-85% = type 1 and 3 collagen -Elastic fibres-2-4% (elastin and fibrilin) -Glycoproteins-facilitate cell adhesion and cell motility -Ground substance between the collagen and elastic tissue -made of glycosaminoglycan/proteoglycan
What is the primary cell found in the dermis?
FIBROBLASTS-synthesises connective tissue
What other cells are present in the dermis?
Histiocytes-immune cells Mast cells Neutrophils Lymphocytes Dermal dendritic cells
describe the vascular supply of the skin?
Blood supply-composed of deep and superficial vascular plexus that so not cross into the epidermis
What 2 tyoes of fibres innervate the skin?
senosory AUTONOMIC INNERVATION of the skin by: ADRENERGIC fibres-innervate ECCRINE and APOCRINE glands(sweat glands that secrete substances by emptying them into a hair follicle) CHOLINERGIC fibres- which innervate the ECCRINE glands in the skin(sweat glands that secrete through a duct onto skin surface)
What is a pilosebaceous unit?
Hair follicle
What muscles are found in the skin?
Arrector pili muscles/arteroles/shunts
How many afferent nerve fibres are in the skin?
One million
What is the structure of nerves in the skin?
BRANCHING NETWORK often occompanying blood vessels to form a MESHG OF INTERLACING NERVES in superficial dermis
Which body parts have more innervation?
Face, extremities and genetilia
How do afferent nerves terminate?
CORPUSCULAR encapsulated nerve ending receptors (dermis) FREE non-encapsulated receptors (epidermis)
What specific nerve receptors are in the dermis?
MEISSNERS CORPUSCLE: -encapsulated -unmyelinated -mechanoreceptors -senses low frequency stimulation at level of the DERMAL PAPILLA -most concentrated in thick hairless skin(finger pads and lips) RUFFINI CORPUSCULE: -Slow acting mechanoreceptor -sensitive to skin stretch -Deeper in the dermis -Spindle shaped -high density around the fingernails -Monitor the slippage of objects PACINIAN CORPUSCLE: -encapsulated -Rapidly adapting mechanoreceptor -Deep pressure and vibration -vibrational role in detecting surface textures -most concentrated in the hands and the feet
What are the receptors in the epidermis?
MERKEL RECEPTOR: -Non-encapsulated -Mechanoreceptor -Light and sustained touch/pressure detection -Oval shaped -In modified epidermal cells-stratum basale directly above the basement membrane -Most populous in fingertips -Also in palms, sores, oral and genital mucosa
What is the microbiome?
gentetic content of the microbioto-bacteria, fungi, and viruses
How much bacteria do we have on the skin?
1 million bacteria/cm2 skin
What are the predominant bacteria on the skin?
-Actinobacteria(including propionibacteria and corynebacteria) -Firmicutes(Clostridia and Bacilli strahylococcus), Bacteroidetes and proteobacteria
why does the composition of microbiota on each niche of the skin vary?
They have different environments
What is the function of the microbiota?
-immune modulation and epithelial health -some bacteria are pro inflammatory -role in disease
What are the 6 functions of the skin?
-Immunological barrier -Physical barrier -Thermoregulationn -Sensation -Metabolic functions -Aesthetic appearence
What is Erithraderma?
A rash that effects 90% of the surface area of the skin0 this can lead to skin failure=at risk of infections, fluid loss, hyperthermia etc
How do immune barrier of the skin work?
LANGERHAN CELLS are in the epidermis and have an equivalent in the dermis called DERMAL DENDRITIC CELLS These rapidly respond to microbial threats and contribute to immune tolerance They have a dense network with which potential invaders MUST interact
What do Langerhan cells do?
-specialised to sense the environment -extend their dendrites through INTERCELLULAR TIGHT JUNCTIONS to sample the outermost layers of the skin=(Stateum corneum) -Interpret microenvironmental context -determine appropriate quality of immune -In absense of danger promote the expansion and activation of skin resident regulatory cells -When sense danger(PAMP)=rapid initiation of innate antimicrobial responses and induction of adaptive responses(T-cells)
What carries out immune surveillance in the dermis?
-Tissue resident T-cells -Macrophages -Dendritic cells
What are endogenous antibiotics in the skin?
-Keratinocyte dervied -e.g Cathelicidin and defensins -iinate immune defense against bacteria, viruses and fungi -They can be chemotactic meaning they can attract immune cells OR they can directly kill bacteria
How does the skin act as a physical barrier to the environment ?
-CORNIFIED CELL ENVELOPE and STRATUM CORNEUM restrict water and protein loss from the skin (this could lead to high output cardiac failure and renal failure in extensive skin disease -SUBCUTANEOUS FAT has important roles in cushioning trauma -UV BARRIER -MELANIN in basal keratinocytes-protection against UV induced DNA damage
How does the skin carry out thermoregualtion?
1-increases blood temp identified by central receptors in skin 2-hypothalumus recieves input and activates SNS responses 3-Vasodialation of peripheral vessels and skin arterioles tot ransfer more heart to the skin surface 4-Activation of eccrine glands to begin sweating 5-Heat leaves the body and blood temperature lowers
What are the metabolic functions of the skin?
-Vitamin D synthesis -Subcutaneous fat- Calorie reserve -Hormone LEPTIN release-sregulates hunger and energy metabolism
How much of the total body fat is in the skin?
80%
What effect does the aesthetic appearance of the skin have on us?
-effects suicide risk -Psychosexual function
What are the 6 functions of the hair?
-protection of the external factors -Sebum-lubricating properties -Apocrine sweat(gives of scents) -Thermoregulation(can make hair stand up or relax) -Social and sexual interaction -Role in injury as it contains Epithelial and melanocyte STEM CELLS that help in recovery
What are the different types of hair?
TERMINAL HAIRS- scalp, eyebrows, and eyelashes VELLUS HAIRS-everywhere else except palm soles, mucosal region of the lips ans external genitalia
What are the 3 major parts of the hair cycle?
ANAGEN(where new hair forms and grows) -85% of hair in this phase -Lasts 2-6 years CATAGEN(regressing phase) -Hair is shrinking -1% of hair in this phase -Lasts 3 weeks TELOGEN (resting phase) -no hair growing -10-15% in this phase -lasts 3 months -Then loss of old hair after this phase and the cycle restarts
What is the structure of hair?
Skin contains PILOSEBACEOUS FOLLICLES (hair follicles) and sweat glands -Hair follicles =pockets of epithelium continuous with superficial epidermis -Hair follicles envelop a small papila of dermis at the base which contains a capillary loop, a nerve fibre and a mucopolysacharide rich stroma -ARRECTOR PILI(smooth muscle), allows the hair to stand up -HOLOCRINE SEBACEOUS GLANDS(OIL GLANDS)-open into the pilary canal ->in axilae follicles assossiated with apocrine glands
What can cause acne?
Hyperactive HOLOCRINE SEBACEOUS GLANDS
What are the 2 sections of the hair follicle?
INFUNDIBULUM- from the opening of the sebaceous gland to the surface of the skin ISTHMUS- between bottom the SEBACEOUS gland and insertion of the ARRECTOR PILI muscle
What does the epithelium keratinisation of the hair begin with?
involves creating an epithelium without the granular layer- ‘trichilemmal keratinisation’
What is the bulge?
-segment of the outer root sheath located at insertion of arrector pili muscle -Hair follicle STEM CELLS are here
What happens to Stem cells in hair follicles?
Stem cells MIGRATE downwards to generate anagen hair follicle-> enter hair bulb matrix and proliferate and undergo terminal differentiation to form hair shaft and inner root sheath
Where do bulge cells move?
upwards to replenish the subaceous gland and proliferate in response to wounding
What are the 3 main parts of the hair follicle?
BULB: -contains the dermal papila and hair matrix -lower portion of the hair follicle OUTER ROOT SHEATH: -reservoir of stem cells originating from the bulge -extends along from hair bulb to infundibulum and epidermis INNER ROOT SHEATH: -guides shape of hair -encloses follicular dermal papilla, mucopoysaccharide rich stroma, nerve fibre and capillary loop
What are the functions of the nail?
-Protect the underlying DISTAL PHALAX -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 structure of the nail and describe?
NAIL PLATE: -final product of proliferation and differentiation of nail matrix keratinocytes -emerges from proximal nail fold -Grows at 1-3mm/month -Firmly attatched to nail bed -Detatches at hyponychium -lined laterally by lateral nail folds NAIL MATRIX: -produce nail plate -Lies under proximal nail fold, above bone of distal phalanx(connected by a tendon) -Lunula only visible proportion -final product of keratinocytes that have lost their nuclei and are completely filled by hard keratins -Also contains melanocytes
What is Psoriasis?
chronic immune mediated skin disorder -arises from a polygenietic predisposition combined with environmental triggers e.g.trauma, infections or medications
What is a common characteristic of Psoriasis?
Sharply demarcated, scaly erythematous plaques
Where are the common sites of Psoriasis
-Scalp, elbows, knees -then nails, hand and feet and trunk
What is the most common systemic manifestation
Psoriatic arthritis Is also assosiated with liver disorders and IBD and is a risk factor for coronary artery disease
Describe the pathophysiology of Psorisis?
1-stress to a keratinocytes=release of DNA or RNA 2-DNA and RNA forms COMPLEXES with antimicrobial peptides (andogineous antibiotics) 3-these complexes induce cytokine(TNF-alpha, IL-1, IFN-alpha) production which activate dermal dendritic cells(dDCs) 4-dDCs migrate to the lymph nodes to promote T helper cell subsets(Th1, Th17, Th22) which release chemokines (cytokines that attract inflammatory cells) 5-this causes the migration of inflammatory cells including CD8s and Neutrophils into the skin 6-These signal for the keratinocytes to proliferate resulting in chronic PSORIATIC PLAQUE
What are some of the clinical feature of Psoriasis?
Genital psoriasis Flexural Psoriasis-not as scaly Palmoplantar Psoriasis-only on soles of hands and feet Subungual hyperkeratosis-too much scale under the nail plate Salmon pink patches-pink stains on nail Oncholysis-raising of the nail characterised by pitting(dints) in nail
If a patient with Psoriasis shows clinical features in nails why is this important?
At a much higher risk of developing Psoriatic arthritis
What is flexural Psoriasis and how is this commonly presented?
These don’t involve chronic plaque Erythrpderma-red skin
What is Guttate Psoriasis
Classic presentation following streptococcheal throat infection, less chronic spotty red dotes on body
What are 3 types of Psoriasis?
Flexural Guttate chronic plaque
How do you manage Psoriasis ?
Change lifestyle factors first: -alcohol(psoriasis can cause liver inflammation and the medicine used can also affect the liver) -smoking(aggravates it ) Dermatologist: to deal with skin symptoms Rheumatologist: -joint symptoms Phycologist: -Depression -Sleep disorders/fatigue -Personality traits/coping All 3 of these specialists can help with: -Pain -Quality of Life -Work diabiltiy Rheum and Dherm can both help with: -Physical functioning -Comorbid diseases Early recognition and treatment is best
What is the therapeutic ladder?
Match severity with treatment
What are topical therapies?
For not as severe Psoriasis: -Vitamin D analogues -Topical corticosteroids -Retanoids(vitamin A analogues) -Topical tacrolimus/pinecrolimus
What is Phototherapy?
Used to treat Psoriasis which is spread over a large amount of the body: -Narrowband UVB -PUVA (psoralen+UVA)
What drug can be given to manage Psoriasis?
SYSTEMIC IMMUNOSUPRESSANTS: -Methotrexate -Ciclosporin -Fumaric acid esters -Apremilast ADVANCED THERAPIES(used if other things don’t work): -Biologic agents ( can target cytokines) -JAK inhibitors(cytokine inhibitors)
What is atopic eczema?
-chronic inflammatory condition that is very ITCHY -complex genetic disease with environmental influences
When is the onset of atopic eczema?
infancy or early childhood
What is atopic eczema assossiated with?
other atopic disorders e.g. asthma, rhinoconjuctivitis
What is another word for eczema?
dermatitus
What are the symptoms of atopic eczema in infants vs children/adults?
Infants: -inflammation of cheeks, scalp, and extensors Children/adults: -Flexural inflammation -lichenification in children and adults
How can you treat atopic eczema?
-Daily emollients and anti-inflammatory therapy
What are the different types of eczema?
-Atopic -Seborrhoiec(dandruff) -venous stasis -allergic contact -irritant contact
Describe the pathophysiology of eczema?
BARRIER DEFECT: -Mutations in protein called FILAGGRIN which binds and aggregates keratin bundles and intermediate filaments to form cellular scaffold in corneocytes in superficial layer of the skin -reduced extracellular lipids in this layer of the skin and impaired ceramide production=INCREASED TRANSEPIDERMAL water loss and impaired PROTECTION against environmental irritant, microbes and allergens -This can all lead to inflammation IMMUNE DISREGUALTION also occurs: -patients have lots of STAPHYLOCOCCUS AUREUS that stimulate Th2 responses and subvert T-regulatory cells(which normally dampen immune response)
What are the clinical features of atopic eczema in different ages?
INFANTS: erythematous, oedematous papule and plaques -blisters leaving erosions Older: -Flexoral distribution -Lichenification(thickening of skin and exaggeration of skin lines) -crusting -dipigmentation -excoriation -fissuring-painful cracks due to dryness -allergy to things e.g nickel and cobalt -Impetiginisation
What is Impetiginisation?
-Gold crust -caused by STAPHYLOCOCCUS AUREUS usually but also stephlococcus
What does venous stasis eczema look like?
-have oedema(excess of watery fluid collecting in the cavities or tissues of the body)
What does Eczema herpeticum present as?
Lots of red dots on the skin -is an emergency because they can spread to internal organs including the brain
How can you treat Eczema herpeticum
Systemic IV antivirals
How is atopic eczema managed?
Most important thing to do is support the barrier function because that is what is lost Lifestyle: -EMOLLIENT mositurisers- to replace moisture in skin -Omission of soap- dries out skin Multidisciplinary team e.g. Clincial Nurse specialist involvement: - teach patients how to correctly application technique of moisturiser -Habit reversal-e.g.scratching Multidisciplinary team - due to it being a co-morbidity disease: -Psychology -Nursing -Dermitology -Allergy paediatricians -dietary aggrevators in children affect the condition(Type 1 allergen) -Patch testing-to look for allergens in adults(type 4 allergens)
If atopic eczema of the nipple does not respond to treatment what do you do?
BIOPSY -because you have to rule out the possibility of it being Padget’s disease- a type of breast cancer which clinically presents the same
There is also a therapeutic ladder for the management of eczema…describe?
TOPICAL THERAPIES: -Topical corticosteroids-correct potency for the correct site -Retinoids(hand dermatitis)(given orally) -Topical tacrolimus/ pinecromilus(unlike steroids they cant thin out the skin) Phototherapy: -Narrow UVB -PUVA(hand dermititis)
What drugs are given to eczema patients?
Systemic immunosuppressents: -Methotrexate -Ciclosporin -Azathioprine -Mycophenolate mofetil Advanced therapies: -Biologics(anti-IL-4-alpha, anti-IL13) -JAK inhibitors
