Lecture 5: Intro to Dermatology Flashcards
Outline the development of skin.
- epidermis originates from ectoderm
- dermis arises from mesoderm that comes into contact with inner surface of epidermis
What is the mesoderm essential for?
inducing differentiation of epidermal structures (e.g. hair follicle)
Overview of structure of skin
- epidermis = superficial layer
- 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 with progressive differentiation/flattening into: Stratum spinosum, Stratum granulosum, Stratum lucidum, Stratum corneum
- cellular progression from basal layer to surface in approx. 30 days
- accelerated in skin diseases (e.g. psoriasis)
What are the only places where the stratum lucidum is found?
palms and soles only
What is significant about the stratum corneum?
no nuclei or organelles
What is the filamentous cytoskeleton of keratinocytes comprised of?
- actin-containing microfilaments
- tubulin-containing microtubules
- intermediate filaments (keratins)
What is the role of keratins?
- structural properties
- cell signalling
- stress response
- apoptosis
- wound healing
What are desmosomes?
- major adhesion complex in epidermis that holds keratinocytes together
- anchor keratin intermediate filaments to cell membrane and bridge adjacent keratinocytes
- allow cells to withstand trauma
What junctions are found in the structure of the epidermis?
- GAP junctions: clusters of intercellular channels, directly form connections between cytoplasm of adjacent keratinocytes, essential for cell synchronization, differentiation, growth etc.
- ADHERENS junctions: transmembrane structures, engage w/actin skeleton
- TIGHT junctions: role in barrier integrity + cell polarity
What other cells are found in the epidermis?
- melanocytes (dendritic, distribute melanin pigment to keratinocytes)
- Langerhans cells (dendritic cells, APCs)
- Merkel cells (mechanosensory receptors)
- mast cells
What is the structure and function of the basement membrane in the skin?
- a.k.a. dermal-epidermal junction
- proteins and glycoproteins (collagens type IV, VII, laminin, integrins)
- roles in cell adhesion and migration
What is the dermis?
- supporting extracellular matrix - provides resilience
What is the papillary dermis?
- superficial
- loose connective tissue
- vascular
What is the reticular dermis?
- deep
- dense connective tissue
- forms bulk of dermis
(less vascular supply)
What is the dermis made of?
- protein (collagen, elastic fibres)
- glycoproteins (fibronectin, fibulin, integrins) - facilitate cell adhesion + motility
- ground substance (between dermal collagen and elastic tissue), GAGs/proteoglycans
What are the primary cells in the dermis?
fibroblasts
What other cells are present in the dermis?
- histiocytes
- mast cells
- neutrophils
- lymphocytes
- dermal dendritic cells (like Langerhans cells in epidermis)
What is the vascular/blood supply of the skin?
- deep and superficial vascular plexus
- doesn’t cross into epidermis
What is the innervation of the skin?
- sensory (free, hair follicles, expanded tips)
- autonomic (cholinergic = eccrine, adrenergic = eccrine and apocrine)
What is the difference between eccrine and apocrine sweat glands?
- eccrine = open directly into surface of skin
- apocrine = open into hair follicle, leading to surface of skin
What is the pilosebaceous unit?
structure consisting of hair, hair follicle, arrector pili muscle and sebaceous gland
What do the nerve fibres providing skin innervation form?
branching network, often accompanying blood vessels, to form a mesh of interlacing nerves in superficial dermis
What nerve ending provides light touch?
Meissner Merkle free
What nerve ending provides touch, pressure?
Merkel, Ruffini, Pacinian free
What nerve ending provides vibration?
Meissner Pacinian
What nerve ending provides sense of temperature?
thermoreceptor
What nerve ending provides sense of pain?
nociceptor (free nerve endings)
What is Meissner’s corpuscle (aka tactile corpuscles)?
- encapsulated, unmyelinated mechanoreceptors
- light touch (+slow vibration)
- senses low-frequency stimulation at level of dermal papilla
- most concentrated in thick hairless skin (finger pads, lips)
What is Ruffini corpuscles (aka Bulbous corpuscle)?
- slow acting mechanoreceptor
- sensitive to skin stretch
- deeper in dermis
- spindle-shaped
- highest density around fingernails
- monitors slippage of objects
What is 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)
What is the microbiome?
- microbiota = bacteria, fungi, viruses
- predominantly actinobacteria, firmicutes, Bacteroidetes and proteobacteria
- composition of each niche depends on environment
- role in immune-modulation and epithelial health
- role in disease
What are the functions of the skin?
- immunological barrier
- physical barrier
- thermoregulation
- sensation
- metabolic functions
- aesthetic appearance
Facts about Langerhans cells?
- dendritic cell
- initiate immune response against microbial threats
- also contribute to immune tolerance
- form dense network
- extend dendritic processes through intercellular tight junctions to sample outermost layers of skin (stratum corneum)
- in absence of danger, promote expansion and activation of skin-resident regulatory cells (Tregs)
- when sense PAMPs = rapid initiation of innate antimicrobial responses
- induction of adaptive response - power and specificity of T cell
What other cells carry out immune surveillance in the dermis?
- tissue resident T-cells
- macrophages
- dendritic cells
Rapid effective immunological backup if epidermis breached
What provides innate immune defense against bacteria, viruses and fungi?
keratinocyte-derived endogenous antibiotics (defensins and cathelicidins)
How does the skin act as a physical barrier?
- against external environment
- cornified cell envelope and stratum corneum restrict water and protein loss from skin
- subcutaneous fat important in cushioning trauma
- UV barrier
- melanin in basal keratinocytes: protection against UV-induced DNA damage
How does the skin play a role in thermoregulation?
- vasodilation or vasoconstriction in deep or superficial vascular plexuses regulate heat loss
- eccrine sweat glands –> cooling effect
- role in fluid balance
What are the metabolic functions of the skin?
- vitamin D synthesis
- subcutaneous fat
- calorie reserve
- 80% of total body fat (in non-obese individuals)
- hormone (leptin) release acts on hypothalamus–> regulates hunger and energy metabolism
Functions of the hair?
- protection against external factors
- sebum
- apocrine sweat
- thermoregulation
- social + sexual interaction
- contains epithelial and melanocyte stem cells
What are the 2 different types of hair?
- terminal hairs –> scalp, eyebrows and eyelashes
- vellus hairs –> rest of body
What are the 3 components of the hair cycle?
ANAGEN: new hair forms and grows (2-6yrs)
CATAGEN: regressing phase (3 weeks)
TELOGEN: resting phase (3 months)
then loss of old hair
What does human skin contain?
pilosebaceous follicles and sweat glands
What are pilosebaceous units?
hair follicles
pockets of epithelium continuous with superficial epidermis
envelope a small papilla of dermis at base
Where are the arrector pili (smooth muscle)?
extends at angle between surface of dermis and point in follicle wall
Which glands open into pilary canal?
holocrine sebaceous glands (in axillae the follicle are associated with apocrine glands)
What is the structure of the hair split into?
- infundibulum: uppermost portion of hair follicle, from opening of sebaceous gland to surface of skin
- isthmus: lower portion of upper part of hair follicle between opening of sebaceous gland and insertion of arrector pili muscle
What does epithelium keratinization begin with?
begins with lack of granular layer named ‘trichilemmal keratinisation’
Hair structure: what is the bulge of hair?
- segment of outer root sheath located at insertion of arrector pili muscle
- hair follicle stem cells reside here
- migrates downward to generate lower anagen hair follicle (enters hair bulb matrix , differentiate to dorm hair shaft and inner root sheath)
- migrates upwards to form sebaceous glands and to proliferate in response to wounding
Hair structure: what is the bulb of hair?
lower most portion of hair follicle, includes follicular dermal papilla and hair matrix (where hair is synthesised)
Hair structure: what is the outer root sheath (ORS) of hair?
extends along from hair bulb to infundibulum and epidermis, serves as reservoir of stem cells
Hair structure: what is the inner root sheath (IRS) of hair?
- guides/shapes hair
- encloses follicular dermal papilla, mucopolysaccharide -rich strome, nerve fibre and capillary loop
What is the function 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 and grooming
Nail structure: what is the nail plate?
- final product of proliferation + differentiation of nail matrix keratinocytes
- emerges from proximal nail fold
- grows at 1-3mm/month
- firmly attached to nail-bed
- detaches at hyponychium
- lined laterally by lateral nail folds
Nail structure: what is the nail matrix?
- produces nail plate
- lies under proximal nail fold, above bone of distal phalanx (to which it’s connected by a tendon)
- lunula only visible proportion
- nail matrix keratinocytes differentiate –> lose nuclei, strictly adherent - cytoplasm completely filled by hard keratins
- also contains melanocytes
Overview of Psoriasis?
- chronic, immune-mediated disorder
- arises from polygenic predisposition combined w/environmental triggers
- pathophysiology includes T-cells + interactions w/DCs and cells involvement in innate immunity, including keratinocytes
- sharply demarcated, scaly, erythematous plaques characterise most common form of psoriasis
- common sites of involvement are scalp, elbows and knees, followed by nails, hands, feet and trunk (including intergluteal fold)
- psoriatic arthritis is most common systemic manifestation
What is the pathophysiology of Psoriasis?
- stressed keratinocytes release DNA/RNA which forms complex w/antimicrobial peptides
- induce cytokine production (TNF and INF alpha and IL-1) which activates dermal dendritic cells
- DCs migrate to lymph nodes, promote Th1, 17 and 22
- leads to chemokine release
- inflammatory cells migrate into dermis
- release cytokines
- keratinocyte proliferation
- psoriatic plaque
How is Psoriasis managed?
- lifestyle: smoking, alcohol, co-morbidities
THERAPEUTIC LADDER - topical therapies: vit D analogues, corticosteroids, retinoids, tacrolimus/pimecrolimus
- phototherapy: narrowband YVB, PUVA
- systemic immunosuppression: methotrexate, ciclosporin, fumaric acid esters. apremilast
- advanced therapies: biologics (anti-TNF etc.), JAK inhibitors
Overview of Atopic eczema?
- intensely pruritic chronic inflammatory condition
- complex genetic disease w/environmental influences
- typically begins during infancy or childhood
- often associated w/other atopic disorders e.g. asthma
- acute inflammation of cheeks, scalp and extensors in infants
- flexural inflammation and lichenification in children and adults
- daily emollients and anti-inflammatory therapy cornerstone of management
- eczema (dermatitis) is umbrella term
What is the pathophysiology of eczema?
BARRIER DEFECT:
- filaggrin binds and aggregates keratin bundles + intermediate filaments to form cellular scaffold in corneocytes
- reduced extracellular lipids + impaired ceramide production
- increased transepidermal water loss
- impaired protection against microbes + allergens
IMMUNE DYSREGULATION:
- staphylococcal superantigens stimulate Th2 responses and subvert T-reg
- T cell infiltrate - bias towards Th2 responses
- eosinophils
- potential role of microbiome?
What are some clinical features of atopic eczema?
- erythematous, oedematous papule + plaques +/- vesiculation
- lichenification, crusting and excoriation
- dyspigmentation or hypopigmentation etc.
- allergic contact dermatitis
- fissuring
- impetiginisation (gold crust, S. Aureus, streptococcus infection)
- venous stasis eczema
- eczema herpeticum (caused by HSV)
How is atopic eczema managed?
LIFESTYLE: - emollients - omission of soap CLINICAL NURSE SPECIALIST INVOLVEMENT: - topical application technique - day treatment - habit reversal - co-morbidities (Patch testing, biopsy) THERAPEUTIC LADDER: - topical therapies: corticosteroids, retinoids, tacrolimus/pimecrolimus - phototherapy - retinoids - systemic immunosuppression - advanced therapies
