Intro to Derm Part 1 Flashcards
describe the embryological formation of the skin
Skin arises by juxtaposition of two major embryological elements:
- Epidermis - originates from ectoderm
- Dermis - arises from mesoderm that comes into contact with inner surface of epidermis
mesoderm is essential for inducing differentiation of epidermal structures (e.g. hair follicle)
describe the cellular changes that occur during the embryological development of skin
week 4 - Epidermis begins to form (from surface ectoderm) as single basal layer of cuboidal cells
week 5 - Secondary layer of squamous, non-keratinising cuboidal cells (periderm) develops on top of the basal layer
periderm generates vernix caseosa - white, waxy protective substance
week 11 - basal layer of cuboidal cells ( stratum germinativum) proliferates to form multilayered intermediate zone
weeks 9-13 - development of hair follicles in stratum germinativum and appearance of lanugo hair (Very fine hair)
weeks 10-17 - epidermal ridges protrude as troughs into developing dermis and neurovascular supply develops into dermal papillae
week 20 - 4 superifical strata have formed - spinosum, granulosum, lucidum, corneum
what is the funciton of the vernix caseosa
where is it produced
during gestation - protects fetus from amniotic fluid during gestation
during birth - protects baby from bacterial and environmental damage
produced by the periderm
label the layers in the development of skin
where is the neruovascular supply in the skin
dermal papillae
(part of dermis and is beneath the epidermis)
what cells give skin, hair, eyes colour
give their sequence of embryological development
melanocytes - contain pigment
precursors are melanoblasts which are derived from the neural crest in the embryo
week 6-8 - melanoblasts migrate dorsally to the developing epidermis, dermis and hair follicles
by week 12-13 - most melanoblasts have reached their destination and differentiate into melanocytes
a subset of melanoblasts form melnaocyte stem cells in hair follicle bulge which are a reserve to replenish differentiated melanocytes
how are melanocytes regulated
with no exposure to external factors
Melanocortin 1 receptor (MC1R), a G protein-coupled receptor regulates quantity and quality of melanins produced:
MC1R is controlled by agonists α-melanocyte-stimulating hormone (αMSH) & adrenocorticotropic hormone (ACTH) and antagonist, Agouti signaling protein (ASP).
Activation of MC1R by agonist (αMSH or ACTH) → causes melanogenic cascade → synthesis of eumelanin (dark pigment)
ASP reverses those effects & elicits production of pheomelanin (pale pigment)
ACTH can also up-regulate expression of the MC1R gene
what effect does ACTH have on pigment produced
how does it do this
increases pigment production
by acting as a MC1R agonist and upregulating gene expression of MC1R on melanocytes
how are melanocytes regulated
using external factors
Exposure to UV
directly increases melanin:
results in Increased expression of MITF & downstream melanogenic proteins, including Pmel17, MART-1, TYR, TRP1, and DCT → increases melanin production
indirectly increases melanin:
also increases PAR2 in keratinocytes → increases uptake & distribution of melanosomes by keratinocytes
how can melanocytes be regulated
either by agonists (ACTH alphaMSH) and antagonist (ASP) of the MC1R receptor
or by UV light exposure
how is the structure of melanocytes related to their function
dendritic cells
processes allow to effectively distribute melanosomes to keratinocytes
give an overview of the structure of the skin
superficial to deep:
epidermis - mostly made up of keratinocytes
basement membrane (dermal-epidermal junction)
dermis - mostly made up of connective tissue
subcutaneous fat
label this diagram of the skin
what is the extra layer of epidermis present in palms and soles of feet only
strutum lucidum
how are keratinocytes able to undergo progressive differentiation
cytoskeleton of keratinocytes is made up of keratin intermediate filaments
filaggrin - protein which regulates progressive differentiation/flattening of keratinocytes from cuboidal to flat
what is the structure of the epidermis
what process occurs in it and how does it happen
composed of keratinocytes
cells layers (superficial to deep):
stratum corneum
stratum lucidum (only present in palms and soles)
stratum granulosum
stratum spinosum
basal layer
progressive differentiation/flattening of keratinocytes occurs - cells progress from the basal layer to surface layer/stratum corneum in 30 days
what are the characteristics of cells in the different epidermal cell layers
basal layer - keratinocytes originate here and are simple cuboidal shaped
stratum spinosum
stratum lucidum - found only in palms and soles
stratum granulosum - cells contain granules of keratohyalin
stratum corneum - keratinocytes are flattened and have no nuclei or organelles, but have specific functions
what is the function of the keratinocytes in the stratum corneum
outer layer - absorb solutes
middle layer - absorbs water
lower/inner layer - mechanical defence barrier, contains lipids e.g. FFA, sterols to carry out its function
how does cellular progression of keratinocytes in erpidermis change in skin disease
it is accelerated
e.g. psoriasis
label this diagram of the epidermis
describe the intracellular structure of keratinocytes:
filamentous cytoskeleton: (from thickest to thinnest)
Tubulin‐containing microtubules (20-25nm)
Intermediate filaments (keratins) (7-10nm)
Actin‐containing microfilaments (7nm)
what is the function of keratins
Structural properties - part of cytoskeleton
Cell signalling
Stress response
Apoptosis
Wound healing
what are desmosomes
where are they found
what is their function
what is their structure
major adhesion complex
found in epidermis
anchors keratin intermediate filaments to cell membrane and bridges adjacent keratinocytes
allows cells to withstand trauma
composed of several smaller proteins - desmoglein, desmocollin, plakoglobin, plakophilin, desmoplakin, keratin
what are the cell to cell connections in the epidermis
desmosomes
gap junctions
tight junctions
adherens junction
what are gap junctions
what is their function
Clusters of intercellular channels (connexons)
Directly form connections between cytoplasm of adjacent keratinocytes
Essential for cell synchronization, cell differentiation, cell growth and metabolic coordination
what are adherens junctions
how do they work
Transmembrane structures
Engage with the actin cytoskeleton of adjacent keratinocytes
label these cell to cell connections
what are merkel cells
where are they
mechanosensory receptors
epidermis
what is the structure of the dermis
2 main layers
papillary dermis:
superificial
connective tissue is loose
vascular
reticular dermis:
deep
dense connective tissue (thicker than papillary dermis)
forms the bulk of the dermis
label the skin below the stratum corneum
give the composition of the dermis
what are the functions of the components
1.Proteins
a)Collagen (80-85% of dermis) – mainly types I and III
very resistant
b)Elastic fibres (2-4%) – fibrillin, elastin
provides elasticity
2.Glycoproteins
fibronectin, fibulin, intregrins facilitates cell adhesion and cell motility
3.Ground substance
glycosaminoglycan / proteoglycan
found between dermal collagen and elastic tissue
maintains hydration, as contains hyaluronic acid which has high water binding capacity
60% of dermis weight is water
what is the structure of collagen found in the dermis
mainly types I and III
collagen is arranged in triple helix ⇒ polymerised into fibres and then fibrils
stabilised by intra and intermolecular cross links ⇒ therefore collagen fibres are very resistant
what are the cells in the dermis
fibroblasts (main cells) - produce connective tissue
Histiocytes
Mast cells
Neutrophils
Lymphocytes
Dermal dendritic cells
(immune cells)
what provides the blood supply to the skin
where is it
deep and superficial vascular plexus
in the dermis (does not cross into epidermis)
describe the afferent nerve innervation of the skin
One million afferent nerve fibers supplying skin
Form branching network, often accompanying blood vessels, to form a mesh of interlacing nerves in superficial dermis
distribution of afferent fibres in skin varies greatly according to body site
face, extremities and genitalia have much more sensory nerve innervation than rest of skin
what are the different nerve endings in the skin
give examples
what are Meissner’s corpuscles
what is its structure
where are they
what is their function
(sensory receptor)
what is the ruffini corpuscle
what is its structure
where is it located
what is its function
what is the pacinian corpuscle
what is its structure
what is its function
where is it found
what are merkel cells
what is their structure
what is their function
where are they found
fill in this table on nerve endings and nerve fibres in skin
what makes up the microbiota of skin
Predominantly composed of:
Actinobacteria (including Propionibacteria and Corynebacteria)
Firmicutes (Clostridia and Bacilli [Staphylococcus] Bacteroidetes
Proteobacteria
but the exact composition of the microbita varies between different parts of the body varies due to the different environment/niche
what does this man have
how will this affect him
erythroderma - over 90% of his body has a rash
skin failure - compromise skin functions:
susceptible to infection
impaired thermoregulation ⇒ heart failure
water loss transepidermally ⇒ kidney failure and high output cardiac failure
how does the epidermis contribute to the skin’s role as an immunological barrier
langerhans cells - involved in adaptive and innate immunity
sentinel cells in epidermis
dendritic processes form dense network in epidermis which invading agents then have to interact with
Extend dendritic processes through intercellular tight junctions to sample outermost layers of skin (stratum corneum)
when they detect PAMPs (released by microbes) ⇒ they rapidly initiate innate immune response
presents antigens to specific CD4 and CD8 t cells (adaptive immune response)
In absence of danger, promote expansion and activation of skin-resident regulatory cells (Tregs)cells
determine the appropriate adaptive immune response (inflammation or immune tolerance) by interpreting the microenvironmental context in which they encounter foreign substances
keratinocytes - innate immunity
produce endogenous antibiotics - defensins and cathelicidins which provide innate defnece against bacteria, viruses and funghi
how does the dermis contribute to the skin’s role as an immunological barrier
Immune surveillance is also carried out in dermis by:
➢Tissue‐resident T-cells
➢Macrophages
➢Dendritic cells
Rapid, effective immunological backup if epidermis breached
what is the role of skin in thermoregulation
central thermoreceptors in hypothalamus and peripheral thermoreceptors - sense temperature of blood
hypothalamus initiates either vasodilatation or vasoconstriction in deep or superficial vascular plexuses → regulate heat loss via skin
also activates eccrine glands to secrete sweat ⇒ causes heat loss due to evaporative cooling effect
