Dermatology 1 Flashcards
How is the skin embryologically formed?
Juxtaposition of the ectoderm (epidermis) and the mesoderm (dermis)
What happens in week 4 of development?
Epidermis forms from a single basal layer of cuboidal cells
What happens in week 5 of development?
Periderm develops along with the Vernix caseosa
What happens in week 11 of development?
Basal layer proliferates to from 4 more superficial strata
What happens in week 9-13 of development?
Hair follicles + lanugo hair form in the stratum germinatium
How do we get the formation of melanocytes?
Derived from neural crest to melanobasts and then differentiation and dorsal migration to epidermis, dermis and hair follicles to form melanocytes
When do melanocytes form?
Week 12-13
What else aside from melanocytes can melanoblasts form?
Melanocyte stem cells for replenishment
How are melanocytes regulated?
MC1R gene (Melanocortin 1 receptor) - regulates the quantity and quality of melanin produced
How does ACTH affect MC1R?
Upregulates MC1R expression
How does a-MSH affect MC1R?
alpha melanocyte stimulating hormone activates MC1R and stimulates a melanogenic cascade and eumelanin production
How does Agouti Signalling protein affect MC1R?
Antagonist - reverse the effects and elicits pheomelanin production
How does UV affect melanocytes?
Exposure leads to increase in MITF. expression and downstream melanogenic proteins. UV exposure also increases PAR2 in keratinocytes to increase melanosome uptake and distribution in keratinocytes
What is the epidermis made up of?
Keratinocytes
Where does division in the epidermis take place?
Basal layer
What are the layers of the epidermis?
Basal layer
Stratum spinosum
Stratum granulosum
Stratum corneum
What layer of epidermic may not always be present?
Stratum lucidum - present in between granular and corneum
What is different about the startup corneum and other epidermal layers?
No nuclei or organelles
How long does the process of cells progressing from basal layer to corner layer take?
30 days - alters with skin disorders
What does the keratinocyte cytoskeleton compose of?
Actin with microfilaments
Tubulin with microtubules
Intermediate keratin filaments
What is the role of keratins?
Structure Cell signalling Stress response Apoptosis Wound healing
What intercellular junctions are found between keratinocytes?
Tight junction
Adherens
Gap junction
Desmosomes
What is the role of desmosomes?
Anchor keratin and bridge adjacent keratinocytes. Have a role in allowing the cell to withstand trauma
What is the role of gap junctions?
Intercellular channels
Connect adjacent keratinocyte cytoplasms
Essential for cell synchronisation, differentiation, growth and metabolic coordination
What is the role of adherens?
Transmembrane
Engage with actin skeleton
What is the role of tight junctions?
Barrier integrity
Cell polarity
What other cells do we find in the epidermis?
Melanocytes
Langerhans cells
Merkel cells
Mast cells
What are melanocytes?
Dendritic cells that distribute melanin in melanosomes to keratinocytes
What are langerhans cells?
Dendritic, antigen presenting cells
What are Merkel cells?
Mechanosensory receptors
What are mast cells?
Immune response
What is the basement membrane?
Dermal-epidermal junction
What is the basement membrane made up of?
Proteins and glycoproteins (collagen IV and VII), laminins and integrins
What is the role of the basement membrane?
Cell adhesion
Cell migration
What is the role of the dermis?
Supporting (ECM) that provides resilience
What are the main 2 layers of the dermis?
Papillary
Reticular
Describe the papillary dermis
Superficial
Loose connective tissue
Vascular
Describe the reticular dermis
Deep
Dense connective tissue
Forms the bulk of the dermis
What is the dermis made up of?
Proteins
Glycoproteins
Ground substance
What proteins make up the dermis?
Collagen (I and III) -80%
Elastic fibres elastin and fibrillin - 3%
What glycoproteins make up the dermis?
Fibronectin
Fibulin
Integrins
What is the role of glycoproteins in the dermis?
Facilitate cell adhesion and motility
What ground substances are found in the dermis?
Glycosaminoglycan
Proteoglycan
Where are ground substances found in the dermis?
Found between dermal collagen and elastic tissue
What is the primary cell of the dermis?
Fibroblasts
What other cells are found in the dermis?
Histiocytes, mast cells, neutrophils, lymphocytes, dermal dendritic cells.
What types of blood supply do we have to the skin?
We have deep and superficial blood supply to make up 3 different vascular plexuses
Where is the vascular plexus/blood supply found?
Subcutaneous plexus is found in the hypodermis
Reticular plexus is found in the reticular dermis
Superficial plexus found in papillary dermis
Does not cross into the dermis.
What innervation do we have in the skin?
Sensory and autonomic
What type of autonomic innervation do we have in the skin?
Cholinergic: eccrine seat glands
Adrenergic: eccrine and apocrine
What areas do we find the most highly innervated at the skin?
Extremities, face and genitalia
What types of afferent nerves do we have?
Corpuscles and free nerve endings
What are corpuscular afferent nerves?
Encapsulated receptors restricted to dermis
What are free afferent nerves?
Non encapsulated crossing into epidermis
Describe meissner’s corpuscle
Encapsulated unmyelinated mechanoreceptor found in the papillary dermis. It’s responsible for sensing light touch (+ slow vibration) and is found in most thick hairless skin e.g. the finger tips.
Describe Ruffini’s corpuscle
Slow acting mechanoreceptor Spindle shaped Deeper in dermis Found in finger nails Monitors skin stretching and slippage of objects
Describe Pacinian (lamellar) corpuscle
Encapsulated mechanoreceptor
Rapid acting
Egg shaped
Senses deep pressure and vibration
Describe Merkel Cells
Non-encapsulated Oval shaped Mechanoreceptor Found in epidermis Detects light or sustained touch and pressure
Where do we find modified epidermal cells?
Stratum basal above the basement membrane. Most commonly found in the finger tips however also in the palms, soles, oral and genital mucosa.
What does the skin microbiome consist of?
Viruses
Fungi
Bacteria
Composition varies with environment
What are the main bacteria we find in the microbiome of skin?
Actinobacteria
Firmicutes
Bacteroidetes
Proteobacteria
What is the role of the skin microbiome?
Immune modulation and epithelial health
Disease
What are the 6 main functions of the skin?
Immunological barrier Physical barrier Thermoregulators Sensation Metabolism Aethetic appearance
How does the skin act as an immune barrier?
Langerhans cells act as sentinel cells and contribute to immune tolerance. However they extend their dendritic processes through intercellular junctions to monitor the external environment
What happens when langerhans cells detect no threat?
They will promote expansion and activation of Treg cells.
What happens when langerhans cells detect PAMPs?
This means they sense danger therefore rapidly activate the innate immune response and induce and adaptive immune response with specific T cells.
What other cells are involved in immune defence of the skin?
Tissue resident T cells, macrophages, dendritic cells also carry out immune surveillance and provide rapid backup tif the epidermis is breached
How does the skin act as a physical barrier?
Stratum corneum and cornfield cell envelope restrict water/protein loss
How might we get visceral problems from extensive skin disease?
Loss of water and protein may be attributed to renal failure/ high output cardiac failure.
What is the role of sub-cutaneous fat in the skin and its physical barrier?
Cushion trauma.
Explain thermoregulation in the skin
Vasodilation/constriction of deep or superficial plexuses to regulate heat loss
Eccrine sweat glands also provide a cooling effect
Role in fluid balance
Explain metabolic functions of the skin?
Vitamin D synthesis
Subcutaneous fat acts as a calorie reserve and releases leptin to act on the hypothalamus and stimulate satiety.
What is the role of basal keratinocytes with melanin in the physical barrier of the skin?
Protect against UV induced damage.
