Special Topics: Human Skin Flashcards
What is skin engineering?
Growing large sheets of skin in the lab to treat burn patients
What is Epidermolysis Bullosa?
This is a condition where mutations occur in the proteins that hold layers of skin together. This causes blistering of the skin and mucous membranes. They are trying to use CRISPR gene editing to resolve this condition
What are keloid scars?
Scars that grow beyond the wound boundary that are itchy and painful
What is the total body surface area?
2m^2
What is the eercentage of total body weight that is skin
7-16%
How thick is the skin in the eyelids?
0.5mm
How thick is the skin of the palm and sole of feet?
4mm or thicker
What are the functions of skin?
Protection/barrier, blood reservoir, vitamin D synthesis, thermoregulation, sensation
What is the most important function of the skin?
Protection/barrier
What does the skin protect the body from?
Environment Chemicals Pathogens Heat UV Water loss
How much blood can the skin hold?
8-10% of the total blood volume
What is the Vitamin D function of the skin?
The skin is the vitamin D precursor. It requires modification by UV before active form can be made in the liver
How do sweat glands contribute to the skins thermoregulation function?
The evaporation of sweat cools the body
What does the constriction of blood vessels do?
Vessel constriction in the dermis reduces blood flow = reduced heat loss
What does vasodilation of blood vessels do?
Vasodilation in the dermis increases blood flow = increased heat loss
What sensations can the skin detect?
Touch/pressure, pain, temperature
What is the top layer of the skin?
The epidermis
What is the function of the epidermis?
To provide a barrier and continued renewal
What does the skin mainly consist of?
Layers of keratinocytes
Why does the skin have no structural strength?
it is mainly made of dead or dying keratinocytes, so there is no connective tissue in the epidermis to provide strength
What are keratinocytes?
are the cells that make up the epidermis and produce keratin filaments which is important for the barrier function of the epidermis (they look like cobblestones under a microscope)
What and where is thin skin?
the majority of skin is thin skin and it is when the epidermis has 4 layers of keratinocytes
What and where is thick skin?
it is in the fingertips, palms, soles and has 5 layers. The fifth layer is Stratum Lucidum
Does the skin have vasculature?
No it doesn’t, all nutrient supply and waste removal through the dermis
What does stratification refer to?
the different layers in the epidermis
What is the function of stratification?
Crucial for barrier function and continued renewal of the epidermis
What do cells at the bottom of the epidermis do?
Keratinocytes proliferate at the bottom of the epidermis (Stratum Basale) which pushes cells up and away from the dermis
What happens to cells as they move away from the dermis?
They undergo programmed cell death
How long does complete epidermal turnover take?
A month
What is the acronym for the layers of the epidermis?
Come Lets Get Sun-Burnt
What is the bottom layer of the epidermis?
Stratum Basale
What are keratinocyte stem cells and what do they do?
They are the reservoirs of cells (keratinocytes, stem cells) for a lifetime of renewal.
Keratinocyte stem cells can divide so that one cell remains a stem cell and the others become transit amplifying keratinocytes
What occurs in the Stratum Basale?
Transit amplifying keratinocytes proliferate (divide rapidly but for a short period before they die) a lot to provide cells for all the top layers
What is the layer above the Stratum Basale?
Stratum Spinosum
How thick is the Stratum Spinosum?
8-10 layers of cells/keratinocytes
What happens to keratinocytes in the Stratum Spinosum
Keratinocytes begin to flatten out
What holds keratinocytes together in the Stratum Spinosum and what is this important for?
Keratin intermediate filaments and desmosomes. This is important for the barrier function of the skin
What layer is above the Stratum Spinosum?
Stratum Granulosum
What happens in the Stratum Granulosum
Flattened keratinocytes undergo apoptosis (programmed cell death)
What are lamellar granules?
Organelles in keratinocytes that fuse to the plasma membrane and begin to release lipid rich secretions to help form the barrier in the Stratum Granulosum
What is keratohyalin?
Protein structure in granules of keratinocytes. These dark granules help form keratin intermediate filaments into keratin (holds keratinocytes together)
What layer is above the Stratum Granulosum
Stratum Lucidum
Where is the Stratum Lucidum found?
ONLY in thick skin (fingertips, palms, soles)
What is the top layer of the epidermis?
Stratum Corneum
How thick is the Stratum Corneum
25-30 layers of flattened dead keratinocytes
What is the function of the Stratum Corneum
To form a barrier to keep moisture in and the outside world out
What are keratinocytes like in the Stratum Corneum
They have finished undergoing apoptosis and are overlapping like the scales of a snake
What is the interface between the dermis and epidermis
The Basement Membrane
What are the proteins in the Basement Membrane
Collagen IV, Perlecan, Nidogen, Laminin 332
What do keratinocytes in the basal layer attach to?
the proteins in the basement membrane
What is the Basement membrane important for?
It is important for the epidermal attachment to the dermis
What can a mutation in the basement membrane proteins cause?
Epidermolysis Bullosa (keratinocytes cannot attach to BM)
What are rete ridges/dermal papillae?
wavelike ridges in the boundary between the epidermis and dermis
What is the function of rete ridges?
their contour provides resistance to shear forces
Where do melanocytes reside?
in the epidermal side of the basement membrane
What do melanocytes make?
Melanosomes
What is contained in melanosomes?
Melanin
How are melanosomes transferred to keratinocytes?
Melanosomes are transferred to keratinocytes by dendrites on melanocytes (36 keratinocytes at a time)
What is melanin?
a pigment that gives skin its colour
What is Pheomelanin
Pigment in Melanin that gives skin red and yellow colours
What is Eumelanin
Pigment in Melanin that gives skin its brown and black colour
What is the function of melanin in keratinocytes?
They form a nuclear cap to protect the nucleus of keratinocytes and its DNA from UV
What is a Langerhan cell?
Intraepidermal macrophage (immune cell in the epidermis)
What is the function of Langerhan cells?
to surveil the epidermis for foreign organisms
What is beneath the basement membrane?
The dermis
What is the dermis made of?
A dense matrix of collagen and elastin fibres (connective tissue)
What are some properties of the dermis
It is strong and supple and, unlike the epidermis, it is very stable with little turnover
Where is the dermis the thickest
in the soles and palms but thickness varies all over the skin
What are fibroblasts?
CT cells that secrete/produce collagen and elastin
Main property of collagen
Strength
Main property of elastin
Elasticity
Names of the layers of the dermis
The Papillary and Reticular Dermis
What is the top layer of the dermis
The Papillary dermis
What is the papillary dermis made of
loose areolar connective tissue
What is the cell density of the papillary dermis
It has a high cell density (can be seen by lots of nuclei)
What is the bottom layer of the dermis?
The Reticular Layer
What is the reticular dermis made of?
Dense irregular connective tissue
What is the cell density of the reticular dermis?
Low cell density (few nuclei)
Is the dermis vascular?
Yes, it contains blood vessels that supply nutrients and remove waste for both dermis and epidermis
What is the function of lamnin in the dermis?
Lamnin lines vessels of vasculature system of dermis
What is the function of Alpha SMA in the dermis?
Alpha SMA is a contractile protei
What are the three types of wounds?
Superficial, partial thickness and full thickness
What are superficial wounds?
wounds that only damage the epidermis
Where do keratinocytes migrate from in wound healing?
Wound edges and dermal appendages (sweat glands, hair follicles, sebaceous glands)
How does wound healing occur in superficial wounds?
Healing occurs by migration of keratinocyte from the wound edges and dermal appendages (sweat glands, hair follicles, sebaceous glands)
Once all keratinocytes are in contact on all sides, then stratification can occur to reform the epidermis
What are partial thickness wounds?
Wounds where all of the epidermis and some of the dermis has been destroyed
What is the first phase of partial thickness wound healing?
Inflammatory phase
What happens in the Inflammatory phase of partial thickness wound healing?
immune cells come in and clean up the wound
What is the second phase of partial thickness wound healing?
Migratory phase
What happens in the Migratory phase of partial thickness wound healing?
keratinocytes migrate from the wound edge and appendages, fibroblasts migrate in to the clot make collagen fibres
What is the third phase of partial thickness wound healing?
Proliferative phase
What happens in the Proliferative phase of partial thickness wound healing?
keratinocytes proliferate
What is the fourth phase of partial thickness wound healing?
Maturation phase
What happens in the Maturation phase of partial thickness wound healing?
epidermal stratification then scab falls off
What is a full thickness wound?
All of the epidermis and dermis is destroyed
Hypodermis can be destroyed too, exposing bone and muscle
Why is wound healing hard in full thickness wounds?
Wound repair is very difficult because all of the reservoirs of epidermal stem cells have been destroyed (wound edges are gone).
What do full thickness wounds heal as?
Scar tissue
Which type of wound is intervention needed?
Full thickness wounds to improve patient outcomes
What is the “gold standard” in healing full thickness wounds
Split thickness grafts which cover the wound
Where does a split thickness graft come from
It takes all the epidermis and part of the dermis from undamaged skin (donor site)
How fast do donor sites heal?
10-14 days
What happened in the first 1-2 weeks post Whakaari/White Island Eruption
Patients were stabilised
What did the first surgery for Whakaari/White Island Eruption
patients do
First surgery was to remove all burnt skin, critical for skin graft success . Any residual necrotic tissue will negatively affect graft take
What did the second surgery for Whakaari/White Island Eruption
patients do
patients received split thickness skin grafts
When is there too much damage to do a split thickness skin graft
Great than 30% of the total body surface area
What are uncovered wound areas covered with
cadaveric skin
What is the function of cadaveric skin
Cadaveric skin acts as a temporary wound dressing, eventually gets rejected
What is an alternative to split thickness skin grafts for burn wound patients
Engineered skin
What is the process of skin engineering
Start with a small sample of undamaged patient skin
Isolate and expand skin cells in the laboratory
Grow enough skin to cover all wounds
Digest sample of patient skin (so it doesn’t get rejected)
Isolate and grow fibroblasts and keratinocytes
Grow large sheets of autologous, full thickness skin
Permanent wound coverage solution
What are the limitations of skin engineering?
No pigmentation
No hair follicles
No sweat glands
No sebaceous glands
What has denovoSkin done?
completed a Phase I clinical trial in 10 patients
of skin engineering (100 fold return on patient skin in 4-6 weeks)
