Dermatology Pt 1 Flashcards
The skin arises from the juxtaposition of 2 major embryological elements. Name them and their origin.
Epidermis - Originates from the ectoderm
Dermis - Arises from the mesoderm that comes into contact with inner surface of epidermis
What is the mesoderm essential for?
Mesoderm is essential for inducing differentiation of epidermal structures (e.g. Hair follicles.
Outline the stages of skin development (include weeks as well).
- Epidermis forms by week 4-single basal layer of cuboidal cells - Superior mesoderm layer.
- Secondary layer of squamous, non-keratinising cuboidal cells (periderm) develops in week 5 - generates white, waxy protective substance - vernix caseosa.
- From week 11, basal layer of cuboidal cells (stratum germinativum) proliferates to form multi-layered intermediate zone → 4 more superficial strata: spinosum (spinous), granulosum (granular), lucidum (clear) and corneum (horny).
- 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.
List the layers of superficial strata of the epidermis from deep to superficial.
Stratum germinativum (basal layer) → Stratum spinosum → Stratum granulosum → Stratum lucidum (found on palms of hands and soles of feet) → Stratum corneum
Where is the stratum lucidum found?
Found on palms of hands and soles only.
What are melanocytes derived from?
Neural crest → Melanoblasts
(Migrate dorsally between week 6-8 to developing epidermis, dermis and hair follicles).
By what week have most melanoblasts reached their destination and differentiated into melanocytes?
Weeks 12-13
What are melanocytes responsible for?
Melanocytes are responsible for melanin secretion, through melanogenesis.
What do a subset of melanoblasts form and why?
Melanocyte stem cells in hair follicle bulge to replenish differentiated melanocytes.
What regulates quantity and quality of melanocytes produced and explain how it is controlled?
Melanocortin 1 receptor (MC1R) → G protein-coupled receptor; Regulates quantity and quality of melanins produced by:
Agonists alpha-melanocyte-stimulating hormone (alpha-MSH) and ACTH mediate melanogenesis via MC1R. Binding of alpha-MSH to receptor ^ melanogenic cascade (tyrosine activity), and eumelanin production. ACTH can also up-regulate expression of MC1R gene.
alpha-MSH + ACTH → MC1R activation → melanogenic cascade → synthesis of eumelanin
Antagonist → Agouti signalling protein (ASP) → reverses effect of agonists and elicits production of pheomelanin.
What does ACTH up-regulate the effect of?
MC1R gene
Explain the regulation of melanocytes in accordance with UV-light.
Keratinocyte receives increased exposure to UV radiation, DNA damage induces mutation.
Increased expression of transcription factor MITF, and downstream melanogenic proteins (Pmel17, MART-I, TYR, TRPI and DCT) → Increases in melanin content.
Increased expression of PAR-2 in keratinocytes → increases uptake and distribution of melanosomes by keratinocytes.
What TF is increased due to UV-light and which downstream melanogenic proteins increase melanin content?
MITF
Pmel-17, MART-1, TYR, TRP1 and DCT
What does UV light cause keratinocytes to express?
PAR-2
What type of cells is the epidermis composed of?
Composed of keratinised, stratified squamous epithelium, avascular structure.
What is the dermis?
Layer of connective tissue and subcutaneous fat, deep to epidermis and separated by BM.
What is the epidermis composed of?
Keratinocytes
How long does cellular progression from basal layer to surface take?
~30 days (accelerated in skin diseases e.g. psoriasis)
What does the filamentous cytoskeleton of keratinocytes (in epidermis) contain?
(Thin) actin-containing microfilaments (7nm)
(Thick) tubulin-containing tubules (20-25nm)
Intermediate filaments (keratin) (7-10nm)
What are the roles of keratins?
Cellular signalling Stress response Structural properties Apoptosis Wound healing
What are desmosomes and what are they made of?
Major adhesion complex in epidermis. Anchor keratin intermediate filaments to cell membrane and bridge adjacent keratinocytes. Allow cells to withstand trauma.
Made up of desmoglein, desmocollin, plakoglobin, desmoplakin, keratin.
What other junctions are found in the epidermis and what are their functions?
Gap junctions - Clusters of intercellular channels (connexons), which directly form connections between cytoplasm of adjacent keratinocytes. Essential for cell synchronisation, differentiation, growth and metabolic coordination.
Adherens - Transmembrane structures which engage with the actin skeleton.
Tight junctions - Role in barrier integrity and cell polarity.
List the cells of the epidermis (not including keratinocytes).
Melanocytes - Dendritic, distribute melanin pigment (melanosomes) to keratinocytes.
Langerhans cells - Dendritic, APCs
Merkel Cells - Mechanosensory receptors
Mast cells
Are the number of melanocytes in people different?
No; number of melanocytes is the same among skin types (eumelanin causes darker skin)
What is considered to be the dermal-epidermal junction, what does this structure consist of and what are its roles/functions?
Basement membrane
Consists of GPs, proteoglycans, collagen IV, VII, laminin and integrin.
Roles in cell adhesion and migration.
Outline the structure of the dermis.
Dermis consists of 2 layers of connective tissue that compose of interconnected mesh of elastin and collagenous fibres produced by fibroblasts. Provides resilience.
Papillary layer - superficial, loose connective tissue, vascular
Reticular dermis - deep, dense, forms bulk of dermis
What proteins are found in the dermis?
Collagen (type I and III) - 80-85% of dermis. Elastic fibres (2-4%) - fibrillin + elastin GPs - Fibronectin, fibulin, integrins - facilitates cell adhesion and motility. Ground substance - Dermal collagen and elastic tissue (Glycosaminoglycan/ proteoglycan)
What is the main cell present in the dermis and also what are the other cells present?
Fibroblasts
Histiocytes, mast cells, neutrophils, lymphocytes and dermal dendritic cells.
What is the vascular supply of the skin?
Deep and superficial vascular plexus, doesn’t cross into epidermis.
Outline the innervation of skin.
Sensory - Free, hair follicles, expanded tips
Autonomic - Cholinergic for eccrine; adrenergic for eccrine and apocrine
(1 million afferent nerves)
What does one pilosebaceous unit consist of?
Hair, hair follicle, arrector pili muscle and sebaceous gland.
What are the 2 types of afferent nerve endings from the skin? Give where they’re found, describe their receptors and examples of each.
Corpuscular - Dermis, encapsulated receptos e.g. Pacinian and meissners.
Free - Epidermis, non-encapsulated receptors e.g. Merkel cell
What are Meissner’s corpuscles?
Encapsulated un-myelinated mechanoreceptors that responds to light touch (+ slow vibration). Senses low-frequency stimulation at level of dermal papilla.
Where are Meissner’s corpuscles most concentrated?
Thick, hairless skin (finger pads and lips)
What are Ruffini corpuscles?
Slow acting mechanoreceptors, sensitive to skin stretch, deep in dermis, spindle-shaped, high density around fingernails and monitors slippage.
aka - Bulbous corpuscles
Where are Ruffini’s corpuscles most concentrated?
High density around fingernails
What are Pacinian corpuscles?
Encapsulated, phasic (rapidly adapting) mechanoreceptor, deep pressure and vibration; vibrational role (detects surface texture); Predominantly found in dermal papillae of hands and feet.
aka - Lamellar corpuscles
What are Merkel cells?
Non-encapsulated mechanoreceptors, detecting light/sustained touch, pressure.
Oval shaped. Modified epidermal cells.
Where are Merkel cells found?
Stratum basale, directly above BM.
Palms, soles, oral and genital mucosa.
Mainly in fingertips.
Which nerve endings detect light touch?
Meissner, Merkel, free
Which nerve endings detect touch, pressure?
Merkel, Ruffini, Pacinian, Free
Which nerve endings detect vibration?
Meissner and Pacinian
Which nerve endings detect temperature?
Thermoreceptor
Which nerve endings detect pain?
Nociceptor (free nerve endings)
What bacteria predominates in the microbiome of the skin?
Predominantly Actinobacteria (including Propionibacteria and Corynebacteria), Firmicutes (Clostridia and Bacili [Staph], Bacteriodetes and Proteobacteria.)
What are the nerve fibres of light touch, pressure/touch, vibration, temperature and pain?
Light touch - A-beta Vibration - A-beta Pressure, touch - A-beta and A-delta Temperature - A-delta and C Pain - A-delta and C
How does the innervation of skin vary for different body sites?
Face, extremities and genitalia have richer innervation than rest body.
What are the functions of the skin?
Sensation Physical barrier Aesthetic appearance Thermoregulation Immunological barrier Metabolism
What are Langerhans Cells?
Dendritic APCs, residing within the basal layer within the epidermis. Initiates immune response and also contributes to immune tolerance.
What are the functions of Langerhans Cells?
Dendritic processes extends through intercellular tight junctions to sample the stratum corneum.
Interpret microenvironmental context → Determines appropriate quality of immune response.
In absence of danger, promote expansion and activation of skin-resident regulatory cells (Tregs).
Detection of PAMPs → rapid initiation of innate antimicrobial responses.
Induction of adaptive immune response: Power and specific of T-cell.
Which cells in the dermis carry out immune surveillance?
Tissue-resident T-cells
Macrophages
DCs
Outline the immune barrier of the skin.
Keratinocyte-derived endogenous antimicrobial peptides are secreted (Defensins, cathelicidins). Expression of cathelicidin is enhanced by keratinocyte activity, predominantly residing within granules of the superficial epidermis → Innate immune defence.
Explain the what the physical barrier formed by the skin is.
Cornified cell envelope and stratum corneum restrict water and protein loss from the epidermis. (High output cardiac failure and renal failure in extensive disease.)
What has an important role in cushioning trauma?
Subcutaneous fat
What protects us against UV-induced damage?
Melanin in basal keratinocytes.
Outline the role of skin in thermoregulation.
Thermoregulatory centre of the hypothalamus detects temperature of blood.
Increase in blood temperature is identified by central receptors; the sympathetic NS is continuously monitoring the body temperature, and initiating appropriate motor responses.
Warm environment - Vasodilation occurs. More blood flows through capillaries, dilating them with the pressure; less blood flows through deeper shunt vessels. More blood flow close to surface - temperature gradient become steeper; cooling by conduction and radiation increased.
Eccrine sweat glands - cooling effect.
List the metabolic functions of the skin.
Vitamin D synthesis
Subcutaneous fat:
Storage via lipogenesis, glucose is converted into triglycerides stored within adipocytes. CALORIE RESERVE
Hormonal - Leptin acts on hypothalamus to regulate hunger and energy metabolism
What hormone acts on hypothalamus to regulate hunger and energy metabolism?
Leptin
List some skin diseases that can affect psychosexual function and can increase the risk of suicide.
Vitiligo
Acne
SLE
Hydradenitis superativa (malodorous inflammatory nodules)
