Introduction to dermatology (24) Flashcards
From where does the epidermis originate?
ectoderm
From where does the dermis originate?
mesoderm that comes into contact w/ inner surface of epidermis
What are the stages of development of the skin?
- epidermis forms by week 4- single basal layer of cuboidal cells
- 2y layer of squamous, non-keratinising cuboidal cells (periderm) develops in week 5–> generates vernix caseosa
- from week 11, basal layer proliferates to form multilayered intermediate zone–> 4 more superficial strata: spinosum (deepest), granulosum, lucidum (only on palms and soles of feet), corneum
- epidermal ridges protrude as troughs into the developing dermis–> dermal papillae
- weeks 9-13 hair follicles develop in stratum germinativum
Which of gliae and melanocytes originate from cells migrating dorsally?
melanocytes: arise from neural crest, differentiate into melanoblasts and migrate dorsally to developing epidermis and hair follicles (wk6-8)–> become melanocytes
N.B. most melanoblasts have reached destination and differentiated into melanocytes by wk 12-13
(those that migrate ventrally become gliae)
How are melanocytes regulated?
MC1R, a G-protein coupled receptor
–> regulates quantity and quality of melanins produced under control of agonists and antagonists
- agonists- aMSH and ACTH–> stimulate melanogenic cascade–> synthesises eumelanin (dark)
- antagonists- ASP- reverses effects–> synthesises pheomelanin (pale)
- ACTH also unregulated MC1R
What is the effect of UV exposure on the regulation of melanocytes?
- inc. expression of MITF transcription factor + downstream melanogenic proteins e.g. Pmel17, MART-1, TYR, TRP1 and DCT–> inc. melanin
- inc. expression of PAR2 in keratinocytes–> inc. uptake and distribution of melanosomes
What is the function of vernix caseosa?
protects developing foetus from amniotic fluid and microbes
What are melanocyte stem cells?
- subset of melanoblasts
- in hair follicle bulge
- replenish melanocytes
What agonists/antagonists regulate melanocyte function?
- agonists: alpha-melanocyte-stimulating hormone (aMSH) AND adrenocorticotropic hormone (ATCH)–> stimulate melanogenic cascade and inc. synthesis of eumelanin (dark pigment)
- antagonists: Agouti signalling protein (ASIP) has opposite effect–> causes production of the phaeomelanin (found in pale skin and red hair)
N.B. ACTH can also upregulate MC1R gene
What is the overall structure of the skin?
- superficial layer= epidermis
- dermis= connective tissue
- subcutaneous fat
What is the structure of the epidermis?
- made of mainly keratinocytes (called corneocytes in stratum corneum)
- keratinocytes divide in basal layer and progressively differentiate
- cellular progression from basal layer to surface takes 30 days: stratum spinosum, stratum granulosum, stratum lucidum*, stratum corneum (no nuclei or organelles)
What does the filamentous cytoskeleton of keratinocytes comprise?
- actin-containing microfilaments
- tubulin-containing microtubules
- intermediate filaments called keratins
What are the roles of keratins?
- structure
- cell signalling
- wound healing
- apoptosis
What are desmosomes?
- cell adhesion complexes
- anchor keratin intermediate filaments to cell membrane and bridge adjacent keratinocytes
- allow cells to withstand trauma
What are gap junctions in the epidermis?
- clusters of intercellular channels (connexons)
- form connections between cytoplasm of adjacent keratinocytes
- essential for cell synchronisation, cell differentiation, cell growth and metabolic coordination
What is the role of tight junctions in the epidermis?
to maintain barrier integrity of skin and cell polarity
What are adherens junctions in the epidermis?
transmembrane structures that hold together actin filaments
What cells are present in the epidermis and what are their roles?
- keratinocytes
- melanocytes: dendritic, distribute melanin pigment in melanosomes to keratinocytes
- Langerhans cells: dendritic, antigen-presenting
- Merkel cells: mechanosensory receptors
- mast cells: role in inflammation
What is the basement membrane of the skin?
- dermal-epidermal junction
- contains proteins and glycoproteins e.g. collagens IV and VII, laminin, integrins
- roles: cell adhesion and migration
What is the structure of the dermis?
- provides resilience, supports skin
- 2 layers: papillary dermis and reticular dermis
- papillary: loose connective tissue, vascular, superficial
- reticular: deep, dense connective tissue, forms bulk of dermis, less vascular supply
What substances are found in the dermis?
- contains mostly collagen I and II, and elastic fibres
- glycoproteins that facilitate cell adhesion and motility: fibronectin, fibulin, integrins
- ground substance between dermal collagen and elastic tissue, composed of glycosaminoglycans and proteoglycans
- hyaluronic acid keeps water in dermis
What cells are present within the dermis?
- primarily fibroblasts (synthesise connective tissue)
- histiocytes
- mast cells
- neutrophils
- lymphocytes
- dermal dendritic cells
What is the innervation and vascular supply to the skin?
- blood supply: deep and superficial vascular plexuses that don’t cross into epidermis
- innervation: sensory and autonomic supply to hair follicles, blood supply, and eccrine and apocrine glands)
- pilosebaceous unit: hair follicles
- arrector pilli muscles
What kind of nerve ending receptors are there in the layers of the skin?
- corpuscular/encapsulated receptors in dermis
- free-ending/non-encapsulated receptors in epidermis
What are the Meissner’s corpuscles?
- tactile corpuscles
- encapsulated, unmyelinated mechanoreceptors
- detect light touch and slow vibration
- at level of dermal papillae
- most conc. in thick, hairless skin (finger pads and lips)
What are the Ruffini corpuscles (also Bulbous)?
- found deeper in dermis
- sensitive to skin stretch
- slow acting mechanoreceptor
- highest density around fingernails
What are the Pacinian corpuscles (also lamellar)?
- rapidly adapting mechanoreceptor
- detects deep pressure and vibration
- ovoid shape
- most conc. in hands and feet
What are the Merkel cells?
- non-encapsulated mechanoreceptors
- detect light/sustained touch and pressure
- modified epidermal cells, found in basal layer, directly above basement membrane
- most populous in fingertips
- also in palms, soles, oral and genital mucosa