5.3 Skin Flashcards
What functions does skin have?
Allows interaction and communication with environment
Protective against mechanical, chemical, thermal, UV and microbial effects (first line of defence)
Interactive, friction for grip and temperature control (sweat)
Immune surveillance against entry of pathogens
Synthetic, produces vitamin D, cytokines, growth factors
Major sense organ (also largest organ) - touch, temperature, pain
Communication (handshakes, smiles, frowns - comms between people or with the environment)
Absorptive, some drugs are able to be absorbed through the skin, i.e. through skin patches (nicotine, hormone replacement, steroid creams)
What are mucosae?
Mucus membranes
What is skin continuous with?
The mucosae (mucus membranes) is the alimentary, respiratory and urogenital tracts
How does skin regenerate?
It is self renewing, with turnover of cells occurring in the epidermis
What are the three layers of skin?
The epidermis, dermis and hypodermis (or subcutis)
What lies beneath the hypodermis?
Subcutaneous fat and then muscle
What is the structure of the epidermis?
Stratified squamous epithelium, with four or five layers
What are the 5 layers of the epidermis from outermost to innermost?
Strateum corneum Stratum lucidum (only seen in thick skin) Stratum granulosum Stratum spinosum Stratum basale/rete ridges
What is the strateum corneum?
The outermost layer of the skin - dead cells. Also known as the cornified layer.
Remnants of dead keratinocytes, including desmosomes, tonofilaments and cornified cell envelope
Layer is thicker in thick skin
Outer layers of dead cells slough off
In what skin is the stratum corneum thickest?
Thick skin
What is the rate of sloughing off of the stratum corneum?
Around 1.5 g total per day, makes up the majority of house dust
What stain can be used to identify cells in the stratum corneum?
Involucrin staining
What is the stratum lucidum?
Another layer of dead cells beneath the stratum corneum, best seen in thick skin.
What is the stratum granulosum or granular layer?
The top living layer of the epidermis - high levels of keratin, new synthesis is reduced. Contains numerous basophilic granules and small keratinosomes.
What do the keratohyaline granules found in the stratum granulosum contain?
Proteins containing sulphur-rich amino acids (i.e. cysteine), specialist linking proteins (involucrin, loricrin, profilaggrin etc).
Good at cross-linking to other cells.
What do the small keratinosomes in the stratum granulosum contain?
Aka Odland bodies
They contain water-repellant lipids
What do keratinosomes, keratinohyaline granules and tonofilaments from together in the stratum granulosum?
They form mature cross-linked keratin under the keratinocyte plasma membrane - the cornified cell envelope.
Once cells die, the contents and granules mix together and form bonds to make the stratum corneum
What are tonofilaments?
Keratin intermediate filaments that make up ‘tonofibrils’ in epithelial cells, looping into the desmosomes
What is the stratum spinosum?
Aka the prickle cell layer
High levels of keratin expression
‘Prickles’ are cellular projections, which allow cell-cell contact and permit attachment to neighbouring cells via desmosomes
The function of the spaces between projections is unknown, potentially for projections from other cells i.e. Langerhans
What is the stratum basale?
Aka the basal cell layer
New keratinocytes are produced here, renews the remainder of the epidermis every 25-30 days
Contains classical stem cells and daughter cells that will divide further to produce keratinocytes (most common) and other skin cell types.
Low columnar or cuboidal cells expressing specific keratin isoforms -> these aggregate to form tonofilaments
Attaches epidermis to underlying basement membrane, very strong attachments
What shape of epithelial cells make up the stratum basale?
Columnar or cuboidal at the base, become more squamous as you go up.
What is the most common skin cell type?
Keratinocytes
What aggregates to form tonofilaments?
Keratin isoforms produced by low cuboidal or columnar epithelial cells in the basale layer
What is the basement membrane directly attached to?
The dermis
Which layer to the classical stem cells of the skin lie?
The stratum basale in the epidermis
What are the ridges in the stratum basale called?
Rete ridges
What is the function of rete ridges within the stratum basale?
They resist force and increase surface area contact between layers to increase strength of connections.
What junction complexes are present in skin?
All of them, just in different proportions: Tight junction Adherens junction Desmosome junction Gap junction Hemidesmosome junction
What is the function of tight junctions?
To seal neighbouring cells together in an epithelial sheet, preventing leakage of molecules between them. Found in upper layers, creating impermeability and preventing Diffusion of growth factors
What is the function of adherens junctions?
Joins an actin bundle in one cell to a similar bundle in a neighbouring cell, holding them together through connecting part of the cytoskeleton
What is the function of a desmosome junction?
They are ‘spot welds’ that anchor the tough intermediate filaments in one cell to those in a neighbour
What is the function of a gap junction?
Cell-cell junction that allows for the passage of small water-soluble ions and molecules
What is the function of a hemidesmosome junction?
Anchors intermediate filaments in a cell to the basal lamina
Which two types of junctional complex are most common/important in skin?
Desmosome and hemidesmosome junctions
How is genetics related to junctional complexes in epithelia?
Genetics controls the intermediate filaments system
What is the lamina lucida?
The less-dense layer of the basal membrane (appears lighter under microscope)
What is the lamina densa?
The more dense layer of the basal lamina (appears darker under microscope)
What connects to the hemidesmosome in each cell?
Intermediate filaments (i.e. tonofilaments and different types of collagen)
What cells types exist in the stratum basale?
Keratinocytes, melanocytes (pigment), Merkel cells (sensory) and Langerhans’ cells (first set of immune cells that are able to respond to antigenic threats entering the epidermal layer)
Where is melanin made?
In melanocytes
What is melanin responsible for?
The different hair and skin colours found in humans
What are the two types of melanosome?
Eumelanosomes (black pigment)
Pheomelanosomes (more red/yellow due to incr in sulphation of proteins)
How and where are melanosomes transferred?
Along cytoplasmic processes into the cytoplasm of basal and stratum spinosum keratinocytes
Exact process is unknown
What is the structure of a melanosome?
Similar to that of a lysosome - simple plasma membrane with a specific content
- What defects can arise from issues in melanosome biology?
Multiple enzymes catalyse formation of melanin pigments in eumelanosomes and pheomelanosomes (tyrosinase in both)
Defects in the pathway result can result in tyrosinase-negative oculocutaneous albinism (OCA1)
Most common form of albinism (lack of pigment, OCA2) affects P gene which in turn reduces eumelanosome contents and protein action (scaffold protein for Tyr, TRP1 and TRP2 production is reduced)
Melanosomes are modified lysosomes, so defects in lysosomal trafficking can result in defects in pigment granules
- From where are melanocytes derived?
The neural crest
- How can neural crest defects cause pigmentation defects?
Defects in neural crest development and migration of melanocytes (need to migrate around body completely from neural crest during embryonic development) result in pigmentation effects
Dominant piebald trait - highly distinctive and conserved pigmentation pattern, from mutation of receptor tyrosine kinase Kit
How is skin colour regulated?
Through stimulation of melanocyte expansion due to UV light from the sun
- What is a Café-au-lait spot?
A pigmented birthmark - increased melanin in this area.
Can be associated with underlying disease, i.e. neurofibromatosis type I
What is a naevus?
A benign tumour of melanocytes (symmetrical, even edges, one shade, smaller than 6mm)
What is a malignant melanoma?
A cancerous tumour of melanocytes (irregular edges and pigmentation, larger than 6mm, uneven edges)
What type of junction is found on ‘prickles’/cellular projections or the stratum spinosum?
Desmosomes - Cadherins present, connect to tonofilaments
How does skin thickness vary?
There is regional variation, either in the thickness of the layer/stratum corneum (usually dictates thickness) or there is some variation in the dermis thickness.
Varies with age
Varies with stretching (i.e. pregnancy)
Varies with hormonal changes (excess cortisol results in thinning)
Where are fingerprints?
On palms and soles
What is the scientific name for fingerprints?
Papillary ridges
Where are the fingerprints derived from?
Ridges in the epidermal layer - sweat glands open onto apex, are inherited and stable throughout life.
What are the hypothesised functions for fingerprints?
Grip
Sensory (receptors Just under epidermis in dermal ridges)
What are nails?
Specialisation of cornified layers - the dorsal aspect of terminal phalanx. Keratin-filled squames in layers
What are nails comprised of?
Nail plate, proximal and lateral nail folds, nail bed
How can nail appearance be used?
As a diagnostic tool
How is skin integrity maintained?
Through: Keratinisation Gap junctions Desmosomes Hemidesmosomes
- What is a genetic disorder that affects connexin?
Vohwinkel syndrome - gap junctions are compromised, leading to deafness and severe keratosis (too much epidermal layer produced, flexion restricted, may require amputation if epidermis reaches bone) at points of flexure in digits.
Dominant connexin 26 mutation
Also involved in control of keratinisation (several other dominant connexin mutations shown to affect keratinisation)
Communication between cells is inhibited/limited, causing these defects.
- What is the result of recessive transglutaminase-1 mutations?
Lamellar icthyosis with severe scaling is the skin - caused by a failure to cross-link proteins in the outer layer of the skin, so skin integrity is lost.
Where is the epidermis derived from?
Ectoderm
Where is the dermis derived from?
Mainly mesodermal
What does the ectoderm exist as before 2 months?
Periderm (epiderm resides below this, periderm is the outermost layer) and epidermis proper
Which cells migrate into the epidermis during weeks 7-8?
Presumptive melanocytes and Langerhans’ cells. Hair follicles begin to develop, growing fine hairs (lanugo) which are shed shortly before or after birth.
What happens to the skin in the 4th month of embryonic development?
Sweat glands bud
What happens in the skin during the 5th month of embryonic development?
Sebaceous gland primordia bud from the hair follicles
What happens to the skin during the 6th month of embryonic development?
The periderm keratinises and desquamates.
How is basal cell proliferation and development regulated?
By signals from the dermis (i.e. keratinocyte growth factor, FGF7) and from the epidermis (Transforming growth factor (TGF)-alpha)
What is the function of TGF-alpha, and effect of upregulation of this gene?
The factor allows for stem cells to be properly stimulated for regulation of epidermal growth. May be unregulated in diseases such as psoriasis (scaly skin)
Where is sonic hedgehog make and what is it’s affect during development?
Made in presumptive hair-forming cells (discovered in mouse epidermis), which instructs underlying dermis to induce further differentiation in the epidermis (feather formation in chicks). Released in regular intervals.
In chicks, neighbouring dermal cells are instructed to not induce follicles -> lateral inhibition, regular spacing.
How many layers are in the dermis?
Upper layer (papillary dermis) Lower layer (more extensive)
What is the upper layer of the epidermis made up of?
Fine network of collagen and elastin with small blood vessels, nerve endings and fibres present.
What is the lower layer of the dermis made up of?
It is the reticular dermis, made up of dense collagen (mainly type 1 which is also found in bone) and long, thick elastin fibres.
- What does loss of elastin in the dermis cause?
Cutis laxa, or sagging of skin
What is the cutaneous plexus?
The blood supply for the hypodermis/dermis junction
What is the subpapillary plexus?
The blood supply for the upper dermis and superficial appendages - papillary loops go up into the reti regisphere but not into the epidermis
What are arteriovenous shunts?
Blood supply that allows for thermoregulation, especially in the dermis of the fingertips, external ear and other extremities.
When too cold, vasoconstriction of this blood supply can cause frostbite.
Look up what glomus bodies are
Do it! Sorry, no WiFi
What is the function of merkel cells and where are they found?
Touch, found in epidermal basal layer.
What is the function of the free nerve endings present in the dermis?
Pain, itch and temperature (may contact Merkel cells)
What is the function of Meissner’s corpuscles and where are they located?
Light touch, and they are found in the dermis.
What is the function of Pacinian corpuscles and where are they located?
Coarse touch, vibration and tension - these are found deep in the dermis.
What is the subcutis/hypodermis?
A variable layer, made up of adipose tissue separated by fibrocollagenous septa.
What is the function of the subcutis/hypodermis?
Food store, thermal insulator and shock absorber.
What makes up the pilosebaceous apparatus?
Hair follicle and shaft, along with other accessory structures such as sebaceous glands and erector pili muscles.
What are the two type of glands?
Eccrine and apocrine.
What is an eccrine gland?
Found in most regions
Simple coiled tubular glands in superficial areas of subcutis
Cholinergic sympathetic control
Involved in thermoregulation and secretion (i.e. sweat glands)
What is an apocrine gland?
Found in very specific regions, such as the breasts, axillae and genital regions
Produce viscous milky secretions which have a foul odour when metabolised by commensal bacteria
Adrenergic sympathetic control (also by female sex hormones)
Make up scent organs in other animals
Where are hairs in the skin found?
Variable - not found in the thick skin of the heel and palms
What surrounds the hair shaft?
A hair follicle, an epidermal downgrowth which extends deep into the dermis and hypodermis.
Where does the hair shaft grow from and why?
From the hair bulb as it contains actively dividing epithelial cells and melanocytes. It also surrounds the dermal papilla (derived from dermis) which contains blood vessels and nerve endings.
What type of muscle is the arrector pili muscle?
Smooth muscle, under sympathetic control. Allows for thermoinsulation in hairy animals through hairs trapping an insulating thicker layer of warm air above the skin (forms goose bumps)
How many sebaceous glands are present per pilosebaceous unit?
One of more
What is the function of the sebaceous glands?
They are oily sebum filling space vacated by inner root sheath breakdown. Cause release of lipids via cellular breakdown (holocrine) which waterproofs and moisturises the skin.
Where are sebaceous glands found independently of hair follicles?
In regions adjacent to body tracts, like the lips.
What causes acne?
Androgen stimulation, follicles become clogged by increased sebum resulting in infection.
What are eccrine and apocrine glands derived from?
The epidermal layer, but reside in the dermal layer.
- What is dystrophic epidermolysis bullosa?
A dominant mutation in the collagen VII gene which results in blistering and scarring of skin due to faults in the connective proteins resulting in skin fragility.
What is essential for the structural integrity of skin?
Cell-cell and cell-basement membrane attachments
These can be affected by defects in connective filaments or in the junctions themselves
- What is epidermolysis bullosa simplex?
Dominant mutations in keratin proteins 5 (type I) and 14 (type II), with recessive mutations also present in plectin coding genes.
Skin integrity is compromised due to faults in connective proteins/structural filaments.
Recessive plectin mutations are also seen in muscular dystrophy (possibly involved with connection of desmin to the sarcolemma)
- What is junctional epidermolysis bullosa?
Failure of function seen in gap junctions, i.e. through recessive mutations in integrin alpha6 and beta4 proteins.
For example, pyloric atresia JEB has these mutations causing intestinal blistering etc and congenital skin absence, especially on the heels and legs although this reason for this is unknown.
Absence of/defects in laminin 5 results in Herlitz JEB, with the common cause of death being respiratory distress.
- What is autoimmune pemphigus foliage is and pemphigus vulgaris?
This is an autoimmune disease where antibodies target desmogleins (Dsg1 and Dsg3, components of cadherin). Pemphigus is a skin blistering disease, as failure to form desmosomes results in cells detaching.
Foliaceus occurs higher up/in the follicles, whereas vulgaris causes extensive deep blistering.
Both are non-intact blisters.
- What increases with severity of epidermolysis bullosa?
Depth of skin at which defect/blistering occurs (dystrophic is most severe form)
What proteins make up the cadherin family?
Desmogleins and desmocollin
What is psoriasis?
An abnormal immune response that leads to excess skin formation and scaling
What is acne?
Where hair follicles become blocked with sebum and can then become infected.
What is eczema?
An excessive immune response resulting in an itchy rash and scaling. May be at site of contact (contact dermatitis) or a more general response to antigen(s) (atopic dermatitis)
Keratinocytes are pushed aside, resulting in inflammation and spongiosis. Sponge-like appearance is observed on a biopsy.
Will often signal the presence of other allergies.
What is vitiligo?
Loss of melanocytes in seemingly random parts of the body, often bilaterally symmetrical
What do psoriasis, acne, eczema and vitiligo all have in common?
They all affect the skin and all have some genetic component, but other factors are also involved.
- What is toxic epidermal necrolysis?
Skin failure, often caused by drugs.
Management of patient is vital as skin breakdown results in sepsis and high mortality rates as no good treatment is available.
Skin can be felt to ‘sheath’ and massively slough off - moisture needs to be maintained.
What is a blister?
A pocket of fluid - clinical relevance depends on location and between which skin layers it resides.
Common cause: friction
Most forms of immune response result in blistering.
Both physical and physiological causes
What is the difference between pemphigoiD and pemphiguS
D for deep
S for superficial
- What is bullous pemphigoid?
An autoimmune issue when antigens at the epidermal-dermal junction are targeted, causing intact blistering. Blistering often seen on patient’s back.
- What is pemphigus gestationis?
An autoimmune response caused by increased number of antibodies due to presence of a foetus, results in blistering.
- What is staphylococcal scalded skin syndrome (SSSS)?
Widespread skin loss and infection caused by staphylococcus bacteria
- What is bullous impetigo?
A localised infection that affects desmogleins (different, rare genetic condition that affects these is called SAM).
Caused by the bacteria staphylococcus Aurelius
- What is icthyosis?
Scaly skin, caused by a mutation that affects filaggrin production.
This protein forms granules in healthy skin but lack of results in scaly skin (icthyosis) and actopic eczema
- What is incontinentia pigmenti?
Recessive sex-linked disease that is fatal in males, and effect is reduced in females through X inactivation. Results in mosaicism, skin changes pigment and has distinctive swirls of lighter and darker pigment as mutation means that cells are more likely to die and undergo apoptosis.
