Skin diseases Flashcards
What are the functions of the skin?
- Protective barrier- physical and chemical
- Involved in mechanical support
- Prevents loss of moisture
- Reduced harmful effects of UV radiation
- Sensory organ- touch, temperature, pressure etc
- Helps regulate body temperature
- Immune organ to detect infections
- Involved in production of vitamin D
- Excretion of waste products
How many distinct layers does the skin have?
3 distinct layers:
- Epidermis - On the outside, consists of layers of epithelial cells and these replace themselves every 2-3 days, it doesn’t have a blood supply - The oxygen and nutrients required for this area actually comes from the capillaries in the lower dermal layer
- Dermis - Middle layer, vascular rich areas, hair follicles, different types of glands, connective tissue rich area
- Hypodermis - Full of adipose tissue
How many distinct layers does the epidermis have?
5 distinct layers:
- Stratum basal
- Stratum spinosum
- Stratum granulosum
- Stratum lucidum
- Stratum corneum
What are the cell types available in the epidermis?
Keratinocytes:
- Main cell type
- Derived from stem cells
- Starts of in the basal areas and as they progress up they become flatter and eventually dead and are shed off
Merkel cells:
- Present in the stratum basal
- Can detect light or discriminatory touch
- Attached to sensory neurone and are found in different locations in the skin
Melanocytes:
- Near the basal region, in the stratum spinosum
- These produce melanin, which protects against UV
- Found throughout the skin
Langerhans cells (APC):
- They are dendritic cells, very important in detecting self and non-self
- They sample the populations of bacteria that live in the surface of the skin and let us know if they are safe
T cells:
- CD8 positive cells, which are ready to attack just incase we have foreign invaders, therefore the dendritic cells can present antigens to the CD8 T cells.
Is the epidermal layer thick or thin?
Thin layer
What is the stratum corneum layer enriched with?
Lipids and keratin
What happens to the skin cells as they age?
They flatten, start to lose their nuclei and eventually die.
What does keratinocytes secrete?
Interleukin-1 beta, which is important in maintaining homeostasis but also in inflammation where the cells can become damaged.
What does melanocytes produce?
Produce melanin in the skin
What is melanin produced from?
Tyrosine
- Tyrosine is metabolised into Dopa and the Dopaquinone by Tyrosinase.
In the presence of Cysteine, what does Dopaquinone become metabolised into?
Pheomelanins, red pigments e.g. people with red hair, freckles etc
How does Dopaquinone become metabolised into Eumelanins?
Dopaquinone becomes metabolised into Leucodopachrome and then Dopachrome.
Eumelanins are the black and brown melanin that are present in darker skin
How many distinct layers does the Dermis have?
2 distinct layers:
- Papillary layer (next to the epidermic layer)
- Reticular layer
What is the papillary layer of the dermis?
- Its about 20% of the dermis
- It’s a very vascular rich region (contains lots of capillaries which release oxygen and nutrients near the epidermis, therefore the bottom layer of the epidermis have sufficient oxygen and nutrients and retain their nuclei. But as you go further away from the oxygen and nutrients, and the capillaries of the dermis, the cells become more flattened in the skin.)
- Lots of connective tissue - particularly collagen
- Papillae’s that stick out which increase the surface area, therefore more exchange of oxygen and nutrients into the epidermis.
What is the Reticular layer of the dermis?
- Takes up majority of the dermis
- Consists of dense irregular connective tissue
- Also consists of elastin and fibrillin. So elastin makes it more elastic and collagen makes it strong
- Consists of several types of immune cells
What are the Meissner’s Corpuscles?
Receptors for light or discriminative touch and up near the epidermal layer.
What are the Pacinian Corpuscles?
These can detect vibration in the skin
What does the root hair plexus do?
Detects fine touch that is detected from the hair shaft, so any movements of the hair shaft. Therefore sensory receptors.
What does the Sebaceous (oil) glands do?
They produce the oil that keeps the skin moist. Also produces the oil that keeps the hair moist and prevents it from cracking.
The oil floats to the surface and protects the outer keratin layers of the skin as well as the hair.
What happens to the sebaceous glands when we get acne in adolescence?
The sebaceous glands can cause problems during adolescence when we get acne, where we get clogging of these sebaceous glands
Where are apocrine sweat glands present?
In the armpit and pubic region.
They produce a protein rich sweat that supports the growth of surface bacteria. They also produce a specific odour.
What kind of sweat does Eccrine sweat glands produce?
They produce extra watery sweat.
How does sweat contribute to regulating body temperature?
When sweat is released onto the skin it evaporates. The amount of sweat that is released can depend on the external temperature, the amount of heat generated by skeletal muscle activity and emotional factors (e.g. sweating when nervous).
Hormones can also release sweat, e.g. during menopause there’s an increase in sweat production for instance with night sweats.
How does the skin on the face differ from other parts of the body?
- In the face we have sebaceous glands connected to the hair shafts and hair follicles.
- There are eccrine sweat glands present
- Environmentally exposed - This is an area that is exposed to the outside all the time
How does the skin on the palm of your hand differ from other parts of the body?
- There is a thick layer of skin - Thick stratum corneum for protection
- Lots of eccrine sweat glands present in the region
- Hairless
How does the skin in the Axilla (armpit area) differ from other parts of the body?
- There are apocrine sweat glands present, which tend to be in more humid areas
- High density of hair
- Occluded, humid environment
What 3 things does the subcutaneous fat layer (hypodermis) act as?
- Mechanical protector (physical protector)
- Thermal insulator (fat is a good insulator)
- Energy store
What does the thickness of the subcutaneous tissue (hypodermis) depend on?
Thickness of the layer depends on the whole body adiposity, therefore how much fat we have in the whole body.
We need a minimal amount to protect our skeleton and organs in our body.
What 2 factors are used in heat regulation?
- Subcutaneous fat pad (hypodermis)
- Skin blood supply
List the immune cells in our skin.
- Langerhans cell (dendritic cells)
- CD8+ T cells
- Keratinocytes
- Dermal dendritic cells
- Plasmacytoid dendritic cells
- CD4 cells (T Helper 1,2 and 17)
- Natural Killer T cells
- Gamma delta T cells
- Macrophages
- Mast cells
- Fibroblast
In what situations is the immune system ready to react in the skin?
- Wound/cut in the skin
- Burn from UV light e.g. sunburn
- Toxins/chemicals or allergic to the skin
- Insect bites
When these happen we mount an immune response and as a result of that we get inflammation.
What different factors cause a signal-mediated response in our keratinocytes and immune cells in the epidermis and the dermis which lead to an inflammatory response?
- Infectious agents: Bacteria, Fungi, Viruses, Parasites etc
- Toxins: Chemical, Radioactive, UV, Biological etc
- Physical stresses: Mechanical, Burns, Trauma, etc
What is the ultimate goal of inflammatory response in the skin?
It is a protective response; We are trying to remove the initial cause of the injury, whether its infectious agents, toxins or physical stresses and repair the damage. Therefore end up with a lot of dead cells, necrotic cells and tissues that need to be destroyed so that it can return back to normal.
What is the purpose of the skin microbiome?
It protects us from disease
What is the downside of skin microbiome?
- Exacerbate skin lesions
- Promote disease
- Delay would healing
What is the skin microbiome?
Collection of all the microbes that live on the human skin such as bacteria, fungi, viruses and mites.
How does microbes directly inhibit pathogen growth?
- They are taking up the space, therefore pathogens don’t have space to grow. They also take up the nutrients on the skin, therefore the pathogens can’t grow because they have nothing to eat.
- They produce AMPs and bactericidal compounds that can kill pathogenic micro organisms.
- They inhibit S.aureus biofilm formation
How do microbes react with the innate immune system locally?
- They help to tune our local cytokine production
- They get presented to the antigen presenting cells which are the dendritic cells/langerhans cells and that helps us to present these antigens to the T cells to be recognised as self.
How to microbes enhance host innate immunity?
- Increase AMP (anti microbial production) production
- Help to decrease inflammation after injury
- Strengthen epidermal barrier
What happens (step by step) if a change occurs in the microbe community?
- A change could be an infection, taking long term antibiotics, or overgrowth, can all change the microbial community living on the skin.
- This can then lead to an inflammatory response on the skin, which then produced proinflammatory cytokines causing inflammation.
- This inflammation can damage the barrier to the skin, which can then allow both the immune system to infiltrate into the area and also get a disrupted physical barrier.
- This then allows microbes to enter areas which they normally would not enter, and penetrate sterile tissues which can cause major problems.
What changes can we have on the skin that can affect the microbes?
- Chronic condition i.e. diabetes - which can cause wounds to occur
- Injury
- Genetic predisposition
This changes the microbial community that’s on the skin, because it can be taken over by potential pathogens and these pathogens can enter areas they shouldn’t and cause an inflammatory response.
This inflammation can then break down the barrier or impair would healing and cause more problems.
What is a wound?
It is a break in the epithelial integrity of the skin. It affects the epidermis but it can affect the dermal layers and even deeper layers, through the hypodermis and muscles and into the bone.
What is a superficial wound?
- Tends to be associated with the epidermal layer
- Damage to the epithelium (outer layer)
- Heals rapidly through regeneration of epithelial cells
- No bleeding as there’s no vascular system in the epidermis
What is a partial thickness wound?
- Involves the dermal layer
- There is bleeding due to vascular damage as its a very rich area for blood vessels
What is a full thickness wound?
- Involves the subcutaneous fat and deeper (even muscle and bone)
- Longest time to heal - new connective tissues required
- Contraction during healing - will take a while for that scar
What are the 4 main stages of wound healing?
- Bleeding : Where bleeding occurs. You get injury to the skin, therefore leading to bleeding and this is called haemostasis because we want to form a blood clot and stop the bleeding.
- Inflammation : In this case we want to stop any infections from occurring, we have lots of immune cells coming into the area, and provide a framework for new blood vessel growth as well.
- Proliferation : In this stage were making more connective tissue, to try and replace the damaged tissue and pull the wounds closed and form a new epidermal layer which is very delicate.
- Remodelling phase : Where we try to bring it back to much to normal as possible, decrease the amount of immune cells in the area and contract the area to what it used to look like and you end up with this avascular scar on the surface.
How long does it take for wound healing to occur?
- Bleeding stage takes less than a day
- The inflammatory stage takes up to anything between 1 - 10 days. But after 1 day is when the neutrophils come in and start to cause inflammation, so it’s peaking after about 1 day. Around about 2-3 days you get granulocytes, macrophages, cytokines etc coming in. You get phagocytosis happening for these few days which is getting rid of the bacteria or any infection that might be around, but also eating up the damaged tissue and getting ridding of the dead tissues so that it can be replaced.
- Proliferation stage: After about 3 days we begin to see proliferation phase and this is where we being to deposit the matrix down. We’re making collagens, fibronectin and proteoglycans which are involved in connective tissue. Also fibroplasia occurring (fibroblasts are proliferating), angiogenesis occurs (new blood vessel formation), re-epithelialization (new delicate cover over the wound) and extracellular matrix synthesis.
- After about 10 days up to 2 weeks to a month, after the wound has occurred, proliferation has ended and onto the remodelling phase. We get a strengthening of this area, increase in tensile strength, decrease of cells in the area and decrease of vascularity in the area. Remodelling the connective tissue and extracellular matrix. This can take up to almost 1 year, for it to get back to normal, depending on how deep the wound is.
What cells and mediators are involved in the inflammation process of acute wound healing?
Neutrophils and macrophages (very important in this stage as they will produce MMPs, ROS, hydrogen peroxide, range of cytokines such as IL and TNF, and growth factors such as VEGF, TGFB, FGF, PDGF)
What cells and mediators are involved in the granulation and neoangiogenesis processes of acute wound healing?
Fibroblasts, macrophages, endothelial cells, MMPs, prolyl hydroxylase, IL, TNF, TGFB, VEGF, PDGF, KGF
What cells and mediators are involved in the re-epithelialization process of acute wound healing?
Keratinocytes, MMPs, EGF, KGF
What cells and mediators are involved in the tissue remodelling process of acute wound healing?
Fibroblasts, collagen fibre cross-linking, MMPs, TGFB
What happens during haemostasis?
- First thing that happens after injury is that blood seeps into the wound.
- Injured vessels contract - to limit the amount of blood that leaks through into the surrounding tissues.
- Coagulation cascade activated by tissue factor very quickly to try and form a clot and limit the leakage and bleeding in the area.
- Clot formation and platelet aggregation
- Platelets trapped in clot release PDGF, IGF, EGF, TGF-B which attract and activate fibroblasts, macrophages and endothelial cells.
- Also release serotonin, which increases vascular permeability - serotonin allows the blood vessels to relax again and increase vascular permeability because you want the immune cells (e.g. neutrophils and monocytes) to come into the area, therefore we need to increase the size of our blood vessels to allow more immune cells to come in.
What happens during early inflammatory phase?
- Activation of complement
- Infiltration of neutrophils within 24-48h
- Diapedesis into wound and phagocytosis of bacteria and foreign particles, with ROS and degrading enzymes - prevent infection and eating up dead tissue
- Dying cells cleared by macrophages or extrusion to wound surface
What happens during late inflammatory phase?
- Blood monocytes arrive and become macrophages (48-72hr)
- Key cell type for repair
- Cytokines and growth factors to recruit fibroblasts, keratinocytes and endothelial cells to repair damage
- Collagenases to degrade tissue
- Poor wound healing when inadequate monocytes/macrophages - Lymphocytes enter wound (>72 hr) and are involved in remodelling
What happens during the proliferative phase (72h-2wks period)?
- Fibroblast migration
- Produce fibronectin, hyaluronan, collagen, proteoglycans
- Proliferate and construct new ECM - Collagen synthesis
- Strength and integrity - Angiogenesis
- TGF beta and PDGF from platelets, TNF and bFGF from macrophages
- Capillary sprouts invade fibrin/fibronectin-rich wound clot and organise microvascular network - Granulation tissue formation
- Mainly proliferating fibroblasts, capillaries, macrophages in matrix of collagen GAGs and fibronectin and tenascin - Epithelialisation
- Single layer of epidermal cells migrate from wound edges to form delicate covering, basal cells increase proliferation, new basement membrane.
- EGF stimulates epithelial mitogenesis and chemotaxis, bFGF and KGF stimulate proliferation
What happens during the remodelling phase (long time period)?
- Matrix matures and remodels
- Fibronectin and HA broken down
- Collagen bundles increase in diameter and strength (80% of strength of original)
- Ongoing collagen synthesis and breakdown by TGF-beta and MMPs
- Collagen becomes more organised and shrink to bring wound margins closer together
- Fibroblasts and macrophages apoptose
- Capillary outgrowth halted and blood flow reduced
- Acellular (no cells around), avascular (no blood vessels) scar results
What happens when the wound does not go back to normal?
You get a chronic wound and impaired wound healing. This usually happens at the inflammatory stage or proliferative stage.
This is due to disturbances in growth factors, cytokines, proteases, cells
What local factors affect wound healing (e.g. post surgical)
- Pressure
-Mechanical injury/trauma - Infection/foreign substances
- Oedema
- Necrosis
- Topical agents
- Lack of oxygen or nutrients delivery (Ischemia)
- Desiccation and dehydration
What systemic factors affect wound healing (e.g. post surgical)
- Old age (cells don’t work as well, collagen is not as strong, elastin is not elasticated enough etc.)
- Obesity
- Chronic diseases e.g. diabetes (most common cause), anemia
- Connective tissue disorders
- Immunosuppression
- Smoking
- Malnuttrition
- Vascular insufficiency
- Stress
- Radiation or chemotherapy
What are the different causes of chronic wounds?
- Neuropathy - Diabetes mellitus, spinal injuries
- Ischemia (lack of oxygen and nutrients in the area) - Atherosclerosis, PVD, Microangiopathy (DM)
- Peripheral oedema - DVT, varicose veins, renal or cardiac failure
- Pressure - Poor mobility, spinal cord injuries, dementia, diabetes mellitus, old age, terminal illness
- Others - Connective tissue disorders leading to vasculitis, systemic diseases, malignancy, smoking, drugs such as corticosteroids and hydroxyurea
What do chronic wounds look like?
- There lots of dead tissue in the area which is hard to get rid of - presence of necrotic and unhealthy tissue
- Excess exudate (the wound is weak) and slough
- Lack of adequate blood supply
- No healthy granulation tissue
- Failure of re-epithelialisation (the wound doesn’t heal over, so you don’t get that cover on the wound so it keeps breaking again)
- Cyclic or persistent pain
- Recurrent wound breakdown
- Clinical or sub-clinical infection
What are the 3 types of neuropathy?
- Motor neuropathy
- Sensory neuropathy
- Autonomic neuropathy
What happens in motor neuropathy that leads to diabetic ulcers?
- You get damage to the neurons and they’re not sending the proper messages.
- This then leads to muscle atrophy and/or bone changes which then leads to a change in gait which causes a deformed foot which ultimately leads to ulcers.
- The change in gait also causes new pressure distribution which causes ulcers
What happens in sensory neuropathy that leads to diabetic ulcers?
- In sensory neuropathy you can’t detect pain, and if you get an injury and you don’t detect the pain then that can lead to a wound which can ultimately lead to an ulcer.
- Ulcers can become infected which can lead to gangrene.
What happens in autonomic neuropathy that leads to diabetic ulcers?
- In autonomic neuropathy you get a decrease in sweating so you get dry skin and cracks in the skin which can cause inflammation and injury causing chronic ulcers.
