Dermatology Intro Flashcards
Where does the Epidermis originate?
Ectoderm
What does the Dermis originate?
Mesoderm
- mesoderm is essential for inducing differentiation of epidermal structures
How does skin come to be??
Juxtaposition between epidermis and dermis
How does the skin develop in utero?
Epidermis is as single basal layer of cuboidal cells ( week 4)
2ndry layer of squamous, non-keratinising cuboidal cells = periderm (week 5)
Generates white, waxy protective substance - vernix caseosa ( protects baby from fluid and after birth from bacteria )
From week 11, basal layer of cuboidal cells ( stratum germinativum) proliferates to form multilayered intermediate zone → four more superficial strata
Epidermal ridges protrude as troughs into developing dermis
beneath neurovascular supply develops into dermal papillae
Weeks 9-13 development of hair follicles in stratum germinativum and appearance of lanugo hair
What are melanocytes?
They are derived from neural crest which forms melanoblasts which migrate dorsally in week 6-8 to develop epidermis and hair follicles
By week 12-13, most melanoblasts have reached destination and differentiate into melanocytes
- Subset of melanoblasts form melanocyte stem cells in hair follicle bulge that replenish differentiated melanocytes
How are melanocytes regulated?
Melanocortin 1 receptor ( MC1R ) and G protein coupled receptor = regulate quality and quantity
Controlled by:
- agonists α-melanocyte-stimulating hormone (αMSH)
- adrenocorticotropic hormone (ACTH) and antagonist
- Agouti signaling protein (ASP).
Activation of MC1R by agonist → melanogenic cascade → synthesis of eumelanin
ACTH can also up-regulate expression of the MC1R gene
What reduces the effects of the melanogenic cascade?
ASP reverses those effects & elicit production of pheomelanin
How does exposure to UV increase melanin content?
Increased expression of MITF & downstream melanogenic proteins, including Pmel17, MART-1, TYR, TRP1, and DCT → increases in melanin content
and
Increased PAR2 in keratinocytes → increases uptake & distribution of melanosomes by keratinocytes
What is the structure of the skin ( top to bottom )
Epidermis : keratinocytes
Basement membrane
Dermis :
Connective tissue
Subcutaneous fat
How are the cells in the basal layer divided? (4)
Progressive differentiation:
( bottom ) dermis -Stratum spinosum -Stratum granulosum -Stratum lucidum (palms and soles only) -Stratum corneum (no nuclei or organelles)
( top )
What is psoriasis an example of?
Cellular progression from basal layer to the surface accelerated to less than 30 days.
What three filamentous cytoskeleton are in keratinocytes?
- Actin‐containing microfilaments (7nm)
- Tubulin‐containing microtubules (20-25nm)
- Intermediate filaments (keratins) (7-10nm)
What are the roles of keratins? 5 ( intermediate filaments )
Structural properties Cell signalling Stress response Apoptosis Wound healing
What are Desmosomes?
Major adhesion complex in epidermis to help cells withstand trauma.
Do this by connecting keratin intermediate filaments to cell membrane and bridge adjacent keratinocytes,
Examples of proteins desmosomes connect?
Desmogelin Desmocollin Plakoglobin Plakophilin Desmoplakin Keratin
What are gap junctions?
Clusters of intercellular channels (connexons)
Directly form connections between cytoplasm of adjacent keratinocytes
What are gap junctions used for?
Essential for cell synchronization, cell differentiation, cell growth and metabolic coordination
What are adherens junctions?
Transmembrane structures
Engage with the actin skeleton
What are tight junctions?
Role in barrier integrity and cell polarity
What are the characteristics of Melanocytes?
epidermis
- Dendritic
- Distribute melanin pigment (in melanosomes) to keratinocytes
- Number of melanocytes = among skin types.
What are the characteristics of Langerhans cells?
epidermis
-Dendritic
-Antigen‐presenting cells
Merkel cells
What are Merkel cells?
epidermis
Mechanosensory receptors
Light / sustained touch, pressure
Oval-shaped
- Mast cells are also found in the epidermis
Characteristics of basement membrane?
( Dermal epidermal junction )
Made of proteins and glycoproteins:
- Collagens (IV, VII), laminin, integrins
Roles:
- Cell adhesion
- Cell migration
describe the papillary dermis?
Superficial
Loose connective tissue
Vascular
Describe the reticulr dermis?
Deep
Dense connective tissue
Forms bulk of dermis
What proteins are found in the dermis?
Collagen (80-85% of dermis) – mainly types I and III
Elastic fibres (2-4%) – fibrillin, elastin
What in the dermis facilitates cell adhesion and motility?
Glycoproteins – fibronectin, fibulin, intregrins
What substance is found between dermal collagen and elastic tissue?
Ground substance:
glycosaminoglycan / proteoglycan
Fibroblasts are the most common cells within the dermis, what other cells are there? ( 5 )
- Histiocytes
- Mast cells
- Neutrophils
- Lymphocytes
- Dermal dendritic cells
Describe the blood supply and innervation to the skin?
Blood supply – deep and superficial vascular plexus
(Does not cross into epidermis)
Innervation:
- Sensory – free, hair follicles, expanded tips
Autonomic:
- Cholinergic – eccrine
- Adrenergic – eccrine and apocrine
What is the Pilosebaceous unit?
The pilosebaceous unit consists of the hair shaft, the hair follicle, the sebaceous gland, and the erector pili muscle
What is the Meisserner’s corpuscle?
- Encapsulated, unmyelinated mechanoreceptors
- Lamellated capsule
Superficial dermis
They are mostly found in thick hairless skin
Sensitive to slow vibration and light touch
What is the Ruffini Corpuscle?
Slow acting mechanoreceptor Deeper in dermis Spindle-shaped Sensitive to skin stretch Highest density around fingernails Monitors slippage of objects
What is the Pacinian corpuscle?
Encapsulated
Rapidly adapting (phasic) mechanoreceptor
Deep pressure and vibration (deep touch)
Vibrational role - detects surface texture
Ovoid
Dermal papillae of hands and feet
What do merkel cells do?
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 & genital mucosa
Where do afferent corpuscular nerves innervate?
Encapsulated receptors in the dermis
e.g. pacinian Messners
Where do afferent free nerves innervate?
Non Encapsulated receptors in Epidermis
Merkel cell
What is the Microbiome required for?
- Host defence
- Immune modulation
- Epithelial health
- Metabolism
What are the functions of the skin?
Immunological barrier Physical barrier Thermoregulation Sensation Metabolism Aesthetic appearance
What characteristics of the skin allow it to become an immune barrier?
Langerhans cells: Initiate immune response in skin
- DC/macrophage
- Sentinel cells in epidermis
- stops autoimmune
- 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)
- (PAMP) → rapid initiation of innate antimicrobial responses
- Induction of adaptive response - T-cells
What cells carry out immune surveillance
- Tissue‐resident T-cells
- Macrophages
- Dendritic cells
- Rapid, effective immunological backup if epidermis breached
What are Defensins and cathelicidins?
Antibiotics made by keratinocytes acting as innate immune defence
How can the skin act as a barrier?
- Cornified cell envelope and stratum corneum restrict water and protein loss from skin – NB high-output cardiac failure and renal failure in extensive skin disease
- Subcutaneous fat cushioning trauma
- UV barrier
- Melanin in basal keratinocytes - protection against UV-induced DNA damage
How can the skin play a part in thermoregultion?
Vasodilatation or vasoconstriction in deep or superficial vascular plexuses → regulate heat loss.
Eccrine sweat glands → cooling effect
Role in fluid balance
Describe the metabolic functions of 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
