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Musculoskeletal and Rheumatology > Lecture 5: Intro to Dermatology > Flashcards

Lecture 5: Intro to Dermatology Flashcards

1
Q

Outline the development of skin.

A
  • epidermis originates from ectoderm

- dermis arises from mesoderm that comes into contact with inner surface of epidermis

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2
Q

What is the mesoderm essential for?

A

inducing differentiation of epidermal structures (e.g. hair follicle)

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3
Q

Overview of structure of skin

A
  • epidermis = superficial layer
  • basement membrane (dermal-epidermal junction)
  • dermis (connective tissue)
  • subcutaneous fat
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4
Q

What is the structure of the epidermis?

A
  • 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)
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5
Q

What are the only places where the stratum lucidum is found?

A

palms and soles only

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6
Q

What is significant about the stratum corneum?

A

no nuclei or organelles

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7
Q

What is the filamentous cytoskeleton of keratinocytes comprised of?

A
  • actin-containing microfilaments
  • tubulin-containing microtubules
  • intermediate filaments (keratins)
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8
Q

What is the role of keratins?

A
  • structural properties
  • cell signalling
  • stress response
  • apoptosis
  • wound healing
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9
Q

What are desmosomes?

A
  • 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
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10
Q

What junctions are found in the structure of the epidermis?

A
  • 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
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11
Q

What other cells are found in the epidermis?

A
  • melanocytes (dendritic, distribute melanin pigment to keratinocytes)
  • Langerhans cells (dendritic cells, APCs)
  • Merkel cells (mechanosensory receptors)
  • mast cells
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12
Q

What is the structure and function of the basement membrane in the skin?

A
  • a.k.a. dermal-epidermal junction
  • proteins and glycoproteins (collagens type IV, VII, laminin, integrins)
  • roles in cell adhesion and migration
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13
Q

What is the dermis?

A
  • supporting extracellular matrix - provides resilience
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14
Q

What is the papillary dermis?

A
  • superficial
  • loose connective tissue
  • vascular
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15
Q

What is the reticular dermis?

A
  • deep
  • dense connective tissue
  • forms bulk of dermis
    (less vascular supply)
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16
Q

What is the dermis made of?

A
  • protein (collagen, elastic fibres)
  • glycoproteins (fibronectin, fibulin, integrins) - facilitate cell adhesion + motility
  • ground substance (between dermal collagen and elastic tissue), GAGs/proteoglycans
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17
Q

What are the primary cells in the dermis?

A

fibroblasts

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18
Q

What other cells are present in the dermis?

A
  • histiocytes
  • mast cells
  • neutrophils
  • lymphocytes
  • dermal dendritic cells (like Langerhans cells in epidermis)
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19
Q

What is the vascular/blood supply of the skin?

A
  • deep and superficial vascular plexus

- doesn’t cross into epidermis

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20
Q

What is the innervation of the skin?

A
  • sensory (free, hair follicles, expanded tips)

- autonomic (cholinergic = eccrine, adrenergic = eccrine and apocrine)

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21
Q

What is the difference between eccrine and apocrine sweat glands?

A
  • eccrine = open directly into surface of skin

- apocrine = open into hair follicle, leading to surface of skin

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22
Q

What is the pilosebaceous unit?

A

structure consisting of hair, hair follicle, arrector pili muscle and sebaceous gland

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23
Q

What do the nerve fibres providing skin innervation form?

A

branching network, often accompanying blood vessels, to form a mesh of interlacing nerves in superficial dermis

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24
Q

What nerve ending provides light touch?

A

Meissner Merkle free

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25
Q

What nerve ending provides touch, pressure?

A

Merkel, Ruffini, Pacinian free

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26
Q

What nerve ending provides vibration?

A

Meissner Pacinian

27
Q

What nerve ending provides sense of temperature?

A

thermoreceptor

28
Q

What nerve ending provides sense of pain?

A

nociceptor (free nerve endings)

29
Q

What is Meissner’s corpuscle (aka tactile corpuscles)?

A
  • 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)
30
Q

What is Ruffini corpuscles (aka Bulbous corpuscle)?

A
  • slow acting mechanoreceptor
  • sensitive to skin stretch
  • deeper in dermis
  • spindle-shaped
  • highest density around fingernails
  • monitors slippage of objects
31
Q

What is Pacinian corpuscles (aka lamellar corpuscles)?

A
  • encapsulated
  • rapidly adapting (Phasic) mechanoreceptor
  • deep pressure and vibration (deep touch)
  • vibrational role - detects surface texture
  • ovoid
  • dermal papillae of hands and feet
32
Q

What are Merkel cells?

A
  • 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)
33
Q

What is the microbiome?

A
  • 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
34
Q

What are the functions of the skin?

A
  • immunological barrier
  • physical barrier
  • thermoregulation
  • sensation
  • metabolic functions
  • aesthetic appearance
35
Q

Facts about Langerhans cells?

A
  • 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
36
Q

What other cells carry out immune surveillance in the dermis?

A
  • tissue resident T-cells
  • macrophages
  • dendritic cells
    Rapid effective immunological backup if epidermis breached
37
Q

What provides innate immune defense against bacteria, viruses and fungi?

A

keratinocyte-derived endogenous antibiotics (defensins and cathelicidins)

38
Q

How does the skin act as a physical barrier?

A
  • 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
39
Q

How does the skin play a role in thermoregulation?

A
  • vasodilation or vasoconstriction in deep or superficial vascular plexuses regulate heat loss
  • eccrine sweat glands –> cooling effect
  • role in fluid balance
40
Q

What are the metabolic functions of the skin?

A
  • 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
41
Q

Functions of the hair?

A
  • protection against external factors
  • sebum
  • apocrine sweat
  • thermoregulation
  • social + sexual interaction
  • contains epithelial and melanocyte stem cells
42
Q

What are the 2 different types of hair?

A
  • terminal hairs –> scalp, eyebrows and eyelashes

- vellus hairs –> rest of body

43
Q

What are the 3 components of the hair cycle?

A

ANAGEN: new hair forms and grows (2-6yrs)
CATAGEN: regressing phase (3 weeks)
TELOGEN: resting phase (3 months)
then loss of old hair

44
Q

What does human skin contain?

A

pilosebaceous follicles and sweat glands

45
Q

What are pilosebaceous units?

A

hair follicles
pockets of epithelium continuous with superficial epidermis
envelope a small papilla of dermis at base

46
Q

Where are the arrector pili (smooth muscle)?

A

extends at angle between surface of dermis and point in follicle wall

47
Q

Which glands open into pilary canal?

A

holocrine sebaceous glands (in axillae the follicle are associated with apocrine glands)

48
Q

What is the structure of the hair split into?

A
  • 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
49
Q

What does epithelium keratinization begin with?

A

begins with lack of granular layer named ‘trichilemmal keratinisation’

50
Q

Hair structure: what is the bulge of hair?

A
  • 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
51
Q

Hair structure: what is the bulb of hair?

A

lower most portion of hair follicle, includes follicular dermal papilla and hair matrix (where hair is synthesised)

52
Q

Hair structure: what is the outer root sheath (ORS) of hair?

A

extends along from hair bulb to infundibulum and epidermis, serves as reservoir of stem cells

53
Q

Hair structure: what is the inner root sheath (IRS) of hair?

A
  • guides/shapes hair

- encloses follicular dermal papilla, mucopolysaccharide -rich strome, nerve fibre and capillary loop

54
Q

What is the function of the nails?

A
  • 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
55
Q

Nail structure: what is the nail plate?

A
  • 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
56
Q

Nail structure: what is the nail matrix?

A
  • 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
57
Q

Overview of Psoriasis?

A
  • 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
58
Q

What is the pathophysiology of Psoriasis?

A
  • 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
59
Q

How is Psoriasis managed?

A
  • 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
60
Q

Overview of Atopic eczema?

A
  • 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
61
Q

What is the pathophysiology of eczema?

A

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?

62
Q

What are some clinical features of atopic eczema?

A
  • 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)
63
Q

How is atopic eczema managed?

A 
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

Musculoskeletal and Rheumatology (5 decks)

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