Dermatology Flashcards
Where does the epidermis originate from?
Ectoderm
Where does the dermis arise from?
Dermis
When does the epidermis form?
Week 4
What happens during the first stage of skin development?
Epidermis forms by week 4- single basal layer of cuboidal cells- superior of mesoderm layer
Which cells form the basal layer during initial stages of skin development?
Cuboidal cells
When does the second stage of skin development occur?
Week 5
What types of cells form the periderm?
Squamous non-keratinising cuboidal cells, generates white waxy protective substance - vernix caseosa
What is the white waxy protective substance that forms the periderm?
Vernix caseosa
Which is the deepest epidermal layer?
Straum germinativum
Stratum basale
Which layers of epidermis forms deep to superficial? (Stage 3)
Straum Spinosum
Stratum Granulosum
Stratum Lucidum (palms and soles)
Stratum Corneum
What do epidermal ridges form?
Dermal papillae
At which weeks do lanugo hair and hair follicles in stratum germinativum form?
Weeks 9-13
How do melanocytes interact with keratinocytes?
Dendritic interactions
What is the principal function of melanocytes?
Responsible for melanin secretion through melanogenesis
Which cells do melanocytes arise from?
neural crest
What term is used to describe progenitor melanocytes?
Melanoblasts
Where do melanocyte stem cells reside?
Hair follicle bulge
Which receptor regulates the quantity of melanin secretion?
Melanocortin 1 receptor (MC1R)- G protein coupled receptor
Which agonist mediates melanogenesis via MC1R?
Alpha-melanocyte stimulating hormone (Alpha-MSH)
What is the rate limiting enzyme in melanogenesis?
Tyrosinase
Which molecule forms the precursor of melanin?
Eumelanin
Which gene increases expression of POMC?
p53
What effect does increased exposure to UV radiation have?
keratinocyte receives increased exposure to UV radiation, DNA damage induces mutation.
Stimulates tumour suppressor gene, p53 –> increases expression of POMC, precursor or alpha-MSH, this increases expression of enzymes and proteins required for synthesis of melanin and melanocytes
Which transcription factors is increases melanogenesis?
MITF
Which downstream melanogenic proteins increase melanin content?
Pmel17, MART-1, TYR, TRP1
DCT
Which melagenic proteins play a role in melanosomes?
MART-1
MPL-1
Increased expression of _____ in keratinocytes increases uptake & distribution of melanosomes by keratinocytes:
PAR-2
How are melanosomes transferred into keratinocytes?
Pseudopodia of melanocyte interlock with keratinocytes, enabling transfer of melanosome; internally degranulates & releases melanin
Which protein reverses effects & elicits production of phenomelanin?
Agouti signalling protein (ASP)
Which hormone up regulates MCIR expression?
ACTH
Which type of epithelial cells form the epidermis?
Composed of keratinised, stratified squamous epithelium
Is the epidermis avascular or vascular?
Avascular
What are the layers (deep to superficial) of the epidermis?
Stratum Basale
Stratum Spinosum
Stratum Granulosum
Stratum Corneum
Which epidermal layer is found exclusively in palms and soles?
Lucidum
Which epidermal layers are keratinocytes located within?
All layers besides stratum basal
Which molecule is stored & synthesised within keratinocytes?
Keratin
What is the function of keratin?
Intracellular fibrous protein that provides strength and water resistance
How are keratinocytes replaced in the stratum corneum?
Replaced by cells from deeper layers
What is the function of the stratum basale?
Attaches epidermis to the basal lamina cells bound to dermis
Basal cells precursors to keratinocytes
Melanocytes produce melanin
Merkel cells
Which structure located on the superficial dermis increases the strength of connection between the epidermis & dermis?
Dermal papilla
Which cells are precursors to keratinocytes?
Basal cells
What is the fate of mitotically produced keratinocytes?
Superficially accumulate away from the stratum basal
What is the function of Merkel cells?
Functions as receptor, responsible for stimulating sensory touch fibres
Where are Merkel cells located?
Stratum Basle
Which epidermal layer contains melanocytes?
Stratum Basale
How are cells connected within the stratum spinosum?
Via desmosomes
What are desmosomes?
Adhesion protein complexes present in the epidermis
Function:Anchor keratin intermediate filaments to cell membrane and bridge adjacent keratinocyte, enables cells to withstand trauma
Where are Langerhans cells located?
Express macrophage function
Why are the cell membranes within the stratum granulosum thick?
Due to keratin presence, and keratohyalin
What granules accumulate within the stratum granulosum?
Lamellar granules,
In which epidermal layer, does the nuclei and cell organelles disintegrate?
Stratum granulosum
What is the most superficial layer of the epidermis?
Stratum corneum
What is the function of the stratum corneum?
Keratininsation of cells prevents penetration of microbes, and the dehydration of underlying tissues.
Provides a mechanical protection against abrasion
How is the dermis separated from the epidermis?
Laye of connective tissue and subcutaneous fat, deep to epidermis, and separated by basement membrane
What is the structure of keratinocytes?
Filamentous cytoskeletons comprise of actin-containinng microfilaments
Tubulin-containing microtubules and intermediate filaments (Keratins)
What are the 5 roles of keratins?
Structural properties Cell signalling Stress response apoptosis wound healing
Connexons are _____ junctions?
Gap junctions
What is the role performed by connexon gap junctions?
Clusters of intercellular channels, directly form connections between cytoplasm of adjacent keratinocytes
What types of junctions are transmembrane structures which engage with actin skeletons?
Adherens junctions
Which type of junctions play a role in barrier integrity and cell polarity?
Tight junctions
Which cells are menlanocytes intimately associated with?
Keratinocytes
How is melanin distributed into keratinocytes?
Formation of a epidermal melanocyte unit, synthesised by melanocytes and disturbed into melanosomes into keratinocyte
What function is performed by Langerhans cells?
Reside within the epidermis as immune sentinels
Cells determine appropriate adaptive immune response (inflammation or tolerance) by interpreting microenvironmental context
Functionally, Langerhans cells express antigen presenting properties; behaving as dendritic cells
Where are Merkel cells located?
Within the basal layer of the epidermis
What is the function of Merkel cells?
Exhibit mechanosensory receptor properties that mediate sense of touch and follicle movement
Which inflammatory host cells reside within the epidermis?
Mast cells
Which Ig mediated reactions?
IgE-mediated reactions through FceRI receptors upon activation
Which main inflammatory cytokine is released from mast cells?
Histamines
The basement membrane is considered to be the ______ junction:
Dermal-epidermal
What comprises the basement epidermal-dermal junction?
Glycoproteins and proteoglycans
Collagen (IV, VII, laminin, integrins)
What is the function of the basement membrane?
Cell adhesion and cell migration
Which cells predominantly produce collagen?
Fibroblasts
Which molecules are found within the dermis?
Compose of interconnected mesh of elastin and collagenous fibres
What is the most superficial layer of the dermis?
Papillary layer
Which epidermal layer does the papillary layer project into?
Stratum basal of the epidermis, projection as dermal papillae
What projections are formed via the papillary layer into the epidermal stratum basale?
Dermal papillae
What type of connective tissue forms the dermis?
Loose areolar connective tissue.
Which two main types of cells reside within the papillary layer?
Adipocytes and fibroblasts
Which touch receptors are located within the papillary layer of the dermis?
Meissner corpuscles
Which dermal layer is deep to the papillary layer?
Reticular layer
Which type of connective tissue forms the reticular layer?
Dense irregular connective tissue
What properties are exhibited by the reticular layer?
Dense irregular connective tissue exhibit multilateral force resistant properties attributing to the flexibility of the skin
Majority of the dermis is comprised of the reticular layer
Which supplies are found within the papillary layer?
Lymphatic capillaries, nerve fibres , and Meissner corpuscles
Where is the sensory, vascular and sympathetic supplies found within the dermis?
Within the reticular layer
Which types of fibres provide elastic properties which facilitate movements within the reticular layer?
Elastin fibres
Which proteins are found within the dermal reticular layer?
Collagen (Type 1 and 3)
Elastin
Fibrillin
Which types of collagen is found within the reticular layer?
Type 1 and 3
Which types of glycoproteins are located within the dermal reticular layer?
Fibronectin, fibrin integrins
Which ground substance molecules are located within the dermal reticular layer?
Dermal collagen, and elastic tissue (glycosaminoglycan and proteoglycan)
Which is the main cell type within the dermis?
Fibroblasts
What are the 6 main cell types in the dermis?
Fibroblasts Mast cells Neutrophils Lymphocytes Histiocytes Dermal dendritic cell
which types of glands secrete sweat?
Sudoriferous glands
What are sweat glands classified as?
Merrocrine glands
Secretions are excreted by exocytosis through a duct
Which types of sweat glands are associated with hair follicles?
Apocrine sweat glands
Which types of sweat glands produce hypotonic sweat for thermoregulation, residing deep in the dermis?
Eccrine glands, duct rising up to pore on skin surface, seat released
Describe the vasculature of the dermis:
Deep and superficial vascular plexus does not cross into epidermis
How are the eccrine and apocrine glands innervated?
Autonomic nervous system
Which type of gland is innervated by cholinergic synapses?
Eccrine
Which glands are stimulated by adrenergic synapses?
Eccrine and apocrine
What is a pilosebaceous unit?
Structure consist of hair, hair follicle, arrector pilli muscle and sebaceous gland
Where are the corpuscles and cutaneous receptors located in respect to afferent nerves?
Located at the terminals of the afferent neurones, encapsulated in elaborate cellular corpuscles.
Which corpuscles responds to light touch, and senses low-frequency stimulation at the level of dermal papilla?
Meissner corpuscles
What is the function of Ruffini corpuscles?
Slow acting mechanoreceptors, sensitive to skin stretch, deep in dermis, spindle-shaped, high density around fingernails, monitors slippage
Where are Ruffini corpuscles predominantly located?
High density around fingernails
Which types of mechanoreceptors detect pressure and vibration?
Pacinian corpuscle
Which endings detect thermal and noxious stimuli?
Free endings
Which three receptors detect light touch?
Meissner
Merkel cells
Free nerve endings
Which receptors detect pressure and touch?
Merkel
Ruffini
Pacinian
Free nerve endings
Which nerve endings detect vibration?
Pacinian
Meissner
Which junctions do the dendritic processes extend through of Langerhan cells?
Tight junctions, to sample the stratum corneum
What is the function of Langerhans cells?
Promotes expansion and activation of skin resident regulatory cells
Detection of pathogen-associated molecular patterns (PAMPs) –> rapid initiation of innate antimicrobial responses
Induction of adaptive responses (power and specific of T cells)
Forms an interlocking network through Langerhans and dendritic interactions which entrap pathogens
What 3 methods is conducted within the dermis to ensure immune surveillance?
Tissue-resident T cells
Macrophages
Dendritic cells
Which antimicrobial peptides are secreted (derived from keratinocytes)?
Defensins
Cathelicidins
What effect does cathelicidin have?
Expression is enhanced by keratinocyte activity, predominantly residing within granules of the superficial epidermis –> Innate immune defence
Which epidermal layer restricts water and protein loss?
Stratum corneum (cornfield cell envelope)
What effect does high output cardiac failure and renal failure have on the epidermis?
Extensive skin disease
What effect does subcutaneous fat exhibit within the skin?
Exhibits shock absorbing properties, protecting muscles and bones from significant impact and traumas
Which type of UV is the epidermis protected from via melanin?
UVB
Which nerve endings exhibit the ability to detect changes in temperature?
Krause end bulbs
Ruffini corpuscles
Which centre detects temperature within the hypothalamus?
Thermoregulatory centre
What occurs in the skin within a warm environment?
Vasodilators occurs, sphincter muscles around the arterioles leading to superficial capillaries are not stimulated to contract and therefore relax.
More flood flow, cooling by conduction and radiation increased
arteriovenous shunt is stimulated to close, thereby enabling greater volume of blood traversing through the capillaries, increased ability of heat loss.
Eccrine glands respond to core internal and peripheral temperature; innervation by cholinergic sympathy nerves stimulates merocrine secretion of hypotonic solutions, secreting water to epidermal surface, where heat is dissipated through evaporation
What is the precursor molecule located within the epidermis for vitamin d?
7-dehydrocholesterol
What is 7-dehydroxycholesterol converted into?
Pre-Vitamin D3
How does UV play a role in the formation of vitamin D3?
Stimulates the action of pre-vitamin D3 conversion into the vitamin D3 within the stratum basale, and stratum spinosum of the epidermis by keratinocyte
Which layer is subcutaneous fat located?
Hypodermis layer
What type of tissue comprises the hypodermis?
Vascularised, areolar connective tissue, and abundant adipose tissue, functions as a mode of triglyceride storage.
How is fat stored in the hypodermis?
Lipogenesis, glucose is converted into triglycerides , stored within adipocytes
What effect does Leptin have?
Adipocytes secrete adipokines including leptin, Stimulates lateral hypothalamic receptors to inhibit hunger, and stimulates satiety
Where does hair root end in the dermis?
Hair bulb
Which structure is surrounded by the hair bulb?
Hair papilla
What does the hair papilla contain?
Contains blood capillaries and nerve endings from the dermis
What are the 6 functions of hair?
Protection against external factors
Sebum: Secreted from associated sebaceous glands, lubricates and waterproofs the hair
Apocrine sweat
Thermoregulation
social and sexual interaction
Epithelial and melanocyte stem cells
Where are the three regions of terminal hairs located?
Scalp, eyebrow, and eyelashes
What type of hair is found on the rest of the body?
Vellus hair
What are the three phases of the hair cycle (in order)?
Anagen
Catagen
Telogen
What is the hair cycle?
Hair grows and is eventually shed, and subsequently replaced by new hair.
What is in the anagen phase?
Hair growth and formation
Cells divide rapidly at the root of the hair, pushing the hair shaft up and out
Basal cells in the hair matrix produce new hair follicles, 85% of hair (2-7 years).
What occurs during the catagen phase?
Regressing phase
Transition from the hair follicles active growth *2-3 weeks
What occurs during the telegenic phase?
Resting phase: Hair follicle at rest, no new growth proceeds
What forms the central core of hair?
Medulla
What forms the layer of compressed keratinised cells around the medulla?
Cortex
What forms the outer layer of hair?
Cuticle
Where are pilosebaceous follicles and sweat glands located?
On the superficial layer of skin with the exception for palms and soles.
Capillary network connects the sebaceous glands to the systemic circulation
What is a pilosebaceous unit?
Sebaceous gland, hair follicles, and the arrector pili muscle
Which is the function of the arrectorr pili muscle?
Contracts in response to nerve signals, from the sympathetic nervous system, enabling the external hair shaft to be erected.
What is the primary purpose for the contraction of arrestor pili muscles?
Entrap a layer of insulated air, essential for thermoregulatory mechanisms
Smooth muscles extends at angle between surface of dermis and point in follicle wall
Where do holocrine sebaceous glands open up in?
Pilary canal –> in axillae
Which sweat glands are hair follicles associated with?
Apocrine glands
Where is the infundibulum located?
Uppermost portion of hair follicle –> opening of sebaceous gland to surface of skin.
Where is the isthmus located?
Inferior region of hair follicle between opening of sebaceous gland and insertion of arrestor pili muscle
What is located within the bulge of hair?
Segment of outer root sheath located at insertion of arrestor pili muscle
The bulge is the location of hair follicle stem cells
What three concentric layers form the wall of hair follicle?
Internal root sheath
External root sheath
Glassy membrane
What does the internal root sheath surround?
Surrounds the root of the growing hair; extend just up to the hair shaft
Cells derived from the basal cells of the hair matrix
Inner root guides and shapes hair
Encloses follicular dermal pailla
The external root sheath is an extension of the ______ encloses the hair root:
Epidermis (infundibulum)
Which cells form the use of the hair root?
Basal cells
Describe the migration pattern to generate lower anagen hair follicle?
Downwards, entire hair bulb matrix, proliferate and undergo terminal differentiation to form hair shaft and inner root sheath
What is the glassy membrane?
Thick, transparent connective tissue sheath covering the hair root, connecting it to the tissue of the dermis
What is the hair bulb?
Lower most portions of hair follicle, includes follicular dermal papilla and hair matrix
What is the nail bed?
Specialised structure of the epidermis, located distally on phalanges and toes.
Nail body is formed on the nail bed, and protects the distal fingers; extremities experiences maximum mechanical stress
What is the nail plate?
Final product of proliferation and differentiation of nail matrix, keratinocytes
Where does the nail plate emerge from?
Proximal nail fold above the bone of distal phalanx
Where does the nail plate attach to?
Nail bed
Where does the nail plate detach?
Hyponychium
Where does the nail matrix reside?
Deep to the proximal nail fold above the bone of distal phalanx
What is the nail matrix?
Keratinocyte differentiation –> Unnucleated and adherent, cytoplasm completely filled by hard keratins, in addition to comprising of melanocytes
What structure does the nail matrix form?
Forms the nail plate
Which proliferating cells form the nail plate?
Cells from the stratum basale
Where does the nail body originally form from?
Nail root
How is the nail body anchored ?
Lateral nail folds, overlaps the nail on the sides, assisting with anchoring the nail body
Where does the nail fold meet?
Meets the proximal end of the nail body at the nail cuticle, the eponychium
What is the term used to describe the thick layer of epithelium over the nail matrix?
Lunula
What are the 5 main functions of nail?
Protection of underlying distal phalanx
Counter-pressure effect to pulp important for walking and tactile sensation
Increase dexterity/ manipulation of small objects
Enhances sensory discrimination
Facilitate scratching or grooming
What type of immune disorder is psoriasis?
Chronic immune-mediated
Polygenic predisposition combined with environment triggers
What are the clinical signs of psoriasis?
Demarcated, scaly, erythematous plaques
What type of plaques form during psoriasis?
erythematous plaques
What is the most common systemic manifestation of psoriasis?
Psoriatic arthritis
What are the common sites of psoriasis?
Scalp, elbows, and knees
Followed by nails, hand, feet and trunk
What is the pathophysiology of psoriasis?
Stressed keratinocytes release DNA/RNA
Forms complex with antimicrobial peptides
Induces cytokines (TNF-a, IL-1 and IFN)
Activates dermal dendritic cells (Langerhans cells in stratum spinosum)
Where do dendritic cells migrate to?
Lymph nodes –> promotes TH1, Th17, th22 cells –> chemokine release - migration of inflammatory cells into dermis –> cytokine release –> keratinocytes proliferation –> psoriatic plaque
Which type of psoriasis is marked with scaly erythematous plaques?
Extensor distribution
What term is used to describe scaling under the nail plate due to excessive proliferation of keratinocytes in the nail ned and hyponychium?
Subungual hyperkeratosis
What occurs during onycholysis?
Separation of nail plate from underlying nail bed and hyponychium
Distal plate discolours
What occurs during pitting?
Sign of partial loss of cells from surface of nail plate, proximal nail matrix psoriasis
What is erythroderma?
Reddening, flaking and thickening of skin
What is guttate psoriasis?
illustrated as red, scaly, teardrop-shaped spots.
Which Vitamin D analogs can be used to manage psoriasis?
Corticosteroids, retinoids (band dermatitis), topical tacrolimus
Which types of phototherapy can be used to manage psoriasis?
Narrowband UVB, PUVA
What is PUVA?
Psoralen and UVA
Which types of systemic immunosuppressants are used to treat psoriasis?
Methorexate
Ciclosporin
Fumaric acid esters
Apremilast
Which advantage therapies are used to manage psoriasis?
Anti-TNF
Anti-IL17
Anti-IL23
JAK inhibitors
What is atopic eczema?
Pruritic chronic inflammatory condition
Complex genetic disease with environmental influences, associated with other atomic disorders
Not in contact with allergen
What other disorders are associated with atopic eczema?
Asthma
Rhino-conjunctivitis
Which areas of the body is acute inflammation associated with?
Cheeks, scalp and extensors in infants
What type of inflammation is common in atopic eczema ?
Flexural inflammation
What treatment is used to manage atopic eczema?
Emollients, and anti inflammatory therapy
What are the common clinical features of atopic eczema?
Infantile phase atopic dermatitis: Erythematous, oedematous papule and plaques.
What type of dermatitis is common due to allergens?
Allergic contact dermatitis
What lifestyle management schemes can be used to treat eczema?
Emollients to prevent desiccation of skin
Omission of soap, topical application technique, day treatment, patch testing and biopsy
Clinical nurse specialist involvement : Habit reversal
What are topical corticosteroids?
Correct potency for correct site, topical tacrolimus
Phototherapy
Retinoids
Systemic immunosuppression
Advanced therapies