Skin :( Flashcards

1
Q

What are the functions of the skin?

A
  • Acts as a protective barrier- physical via cells being packed together and chemical due to its oils and antimicrobial peptides
  • mechanical suppirt
  • Prevents water/moisture loss
  • Decrease effects of uv radiation
  • sensory organ- has receptors for temp, touch, pressure
  • Regulates body temperature
  • Excretion of waste products e.g. sweat
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2
Q

What are the 3 layers of the skin?

A

Epidermis- epithelial cell layers, no blood supply- replaced every 2-3 days

Dermis- Middle layer- vascular-rich, hair follicles. Has a lot of connective tissue (collagen, fibrin and elastin) and nerve endings

Hypodermis- Made up of adipose tissue. Has a fat layer which aids mechanical protection, insulation and an energy store.

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3
Q

What are the 5 layers of the epidermis?

A

Stratum basale
Stratum spinosum
Stratum granulosum
Stratum lucidum
Stratum corneum

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4
Q

What cell types are found in the epidermis?

A
  • Keratinocytes- basal areas as cuboidal cells- as you reach the surface of the skin, these flatten (work up to surface over 3-4 days and flatten, they then die and flake off due to no access to blood supply near the surface). They are stem cells that can rapidly proliferate and differentiate allowing skin to constantly be renewed. They make keratin which is a component of skin, nails and hair. can also produce cytokines e.g IL-1 AND 6.
  • Merkel cells- In startup basal- have receptors that detect light or discriminative touch and is connected to sensory neurones. Protects us from harm as we can feel pain

-Melanocytes- near the basal layers- they produce melanin- to protect the skin from UV and decrease number of DNA mutations (and gives our skin its colour). Melanin is produced by tyrosine and catalysed by tyrosinase

  • Langerhans cells- are dendritic cells they detect self and non-self by sampling bacteria on the skin and presenting antigens to cd8+ t-cells
  • T-cells- CD8+ t-cells are ready to react in case of foreign organism
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5
Q

What are the 2 corpuscles in the skin and their roles?

A
  • Meissner’s corpuscle- has receptors for light and discriminative touch
  • Pacinian corpuscle- detect vibrations
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6
Q

What do the sebaceous glands do?

A

Produce and secrete sebum which is an oily substance that keeps the hair and skin moisturised. (oil flows to surface to protect hair and skin)

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7
Q

What are the difference between the eccrine and apocrine sweat glands?

A
  • Appocrine glands- only found in the armpit, breast and pubic regions. differ from eccrine glands in that they are larger and open into hair follicles instead of onto the skin surface. Produces a thicker sweat, with the typical ‘sweat’ smell
  • Eccrine sweat glands- are found over most of the body (most numerous on the feet and palms of the hands) (only not found on the lips, ear canal, nail beds and genital areas). They. open directly onto the skin’s surface and secrete a clear, thin watery sweat that cools the body.
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8
Q

Discuss the appendages found on the skin (like an exam q)

A
  • Appocrine glands- only found in the armpit, breast and pubic regions. differ from eccrine glands in that they are larger and open into hair follicles instead of onto the skin surface. Produces a thicker sweat, with the typical ‘sweat’ smell
  • Eccrine sweat glands- are found over most of the body (most numerous on the feet and palms of the hands) (only not found on the lips, ear canal, nail beds and genital areas). They. open directly onto the skin’s surface and secrete a clear, thin watery sweat that cools the body.
  • Sebaceous glands - Produce and secrete sebum which is an oily substance that keeps the hair and skin moisturised. (oil flows to surface to protect hair and skin)

Hair follicles- the hair shaft is the part that is above the skin that sits in the hair follicle. It is important to keep the body warm and regulating body temperature and also has a sensory function and mechanical protection.

Also nails- made of keratin . They allow us to grip, protect the fingertips which are rich in blood vessels and nerve endings and judge how to hold things, detecting pressure changes and increasing the sensitivity of our fingertips.

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9
Q

How does the skin vary throughout the body?

A

FACE
- High density of sebaceous glands and hair and eccrine glands
- Is exposed to the environment

Palm of hand
- is hairless
- Has a thick stratum corneum which provides protection
- High density of eccrine glands

Axilla (armpits)
- lots of apocrine glands
- High hair density
- Has a humid environment

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10
Q

What cells are involved in the immune system of the skin?

A

In the Epidermis:
- Langerhans (dendritic cells)- these are antigen-presenting cells and present foreign antigens to CD8+ t-cells
- Keratinocytes- Produce cytokines e.g. IL-1 and IL-6

In the dermis:
- CD4 helper t-cells
- NK cells
- macrophages
- mast cells
- fibroblasts
- neutrophils

Melanocytes- produce melanin which protects the skin against uv damage and decrease number of DNA mutations.

Merkel cells- sensory- prevents ongoing harm due to us being able to feel pain

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11
Q

What causes acne?

A

When bacteria blocks sebaceous glands

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12
Q

What does it mean that the skin microbiome is bi-directional?

A

The large skin microbiome is beneficial to us and we are beneficial to them. As we provide the bacteria etc with nutrients and space and they protect us from foreign organisms.
- They inhibit pathogen growth by taking up the space and nutrients an react with innate immune system= local cytokine production, priming antigen presenting cells
- exhausts host innate immunity- train to recognise self and foreign organisms by priming antigen presenting cells

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13
Q

What are the four stages of acute wound healing?

A

Haemostasis- microvascular injury occurs = blood seeps into the wound:
- Injured vessels contract
- Coagulation cascade activated by tissue factor = clot formation and platelet aggregation
- platelets trapped in the clot release PDGF, IGF which attract fibroblasts, macrophages, endothelial cells and serotonin (increases vascular permeability)
= stops bleeding

INFLAMMATORY PHASE: split into early and late
- Activation of complement system
- Infiltration of neutrophils occurs within 24-48 hours
- Diapedesis into wound and phagocytosis of bacteria and foreign particles with ROS (reactive oxygen species) and degrading enzymes = prevent infection
late:
- Monocytes arrive and become macrophages within 48-72 hours and these are very key for repair!
- pro-inflammatory Cytokines and growth factors e.g. TNF, MMPs recruit other immune cells to repair the damage
collegenases degrade tissue
Lymphpocytes enter around 72 hours and are involved in remodelling

PROLIFERATIVE:
- occurs over 72-hours to 2 weeks
- Fibroblasts migrate to the area= produce collagen, fibronectin, proteoglycans = proliferate and construct a new ECM
- Collagen synthesis also increases strength and integrity
- Angiogenesis occurs- formation of new blood vessels to provide oxygen and nutrients to aid repair. Capillary sprouts invade the fibrin-rich clot and organise a microvascular network
- Epithelialisation occurs- a thin, single layer of epidermal cells migrate from wound edges to form a delicate covering over the wound.

  • REMODELLING: takes a long time
  • The matrix matures and remodels
  • Fibronectin and hylauronic acid breakdown
  • Increased collagen synthesis- more organised and shrinks the margins closer together
  • Fibroblasts and macrophages apoptose
  • least to formation of an acellular and avascular scar

IN CHRONIC WOUNDS (e.g. caused by neuropathy in DM, connective tissue disorders, peripheral oedema, ischaemia) - these normal phases are disrupted- usually at inflammatory or proliferative
- leads to disturbance in growth factors, cytokines, cells
= Necrotic and unealthy tissue, excess exudate, lack of adequate blood supply, failure or re-epithelialisation, persistant pain, recurrent wound breakdown, infection

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14
Q

What happens during haemostasis during wound injury?

A
  • Microvascular injury causes blood to seep into the wound
  • the injured vessels contract to try and limit blood loss
  • coagulation cascade activated by tissue factor = formation of clots and platelets to aggregate
  • Platelets are trapped in the clot and released PDGF, IGF, EGF, TGFB = these attract and activate fibroblasts, macrophages, neutrophils
  • Also releases serotonin- this increases vascular permeability to easily allow immune cells through
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15
Q

What factors affect wound healing e.g. post surgery?

A

LOCAL
- pressure e.g. bed sores
- mechanical injury
- infection
- oedema
- necrosis
- lack of oxygen and nutrients- ischaemia
- dehydration of skin

SYSTEMIC
- old age
- obesity
- chrons
- immunosupression
- smoking
- malnutrition
- stress
- radiotherapy or chemotherapy

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16
Q

What are the symptoms of eczema/dermatitis?

A

Dry, irritated, inflamed skin
red
oedema
ooszing
papules
crustiness
scaring
itchiness
dry skin
- often flexural - knees, elbows, wrists

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17
Q

What are the causes of eczema/atopic dermatitis?

A

Genetic predisposition
Defect in filaggrin gene- important for maintaining skin barrier
Defects in skin barrier
Abnormalities in normal inflammatory and allergy responses
Barrier defects

18
Q

What are the treatments for eczema/atopic dermatitis?

A

Keep skin moist!
- Use emollients e.g. E45 to moisten skin
- Topical corticosteroids
- Antibiotics- only if becomes infected
- Phytotherapy

If these are all inadequate:
- Systemic corticosteroids
- Topical calcineurin inhibitors e.g. tacrolimus - prevent t-helper cells from secreting il-4
- Immunosuppressants e.g. azathioprine, ciclosporin
- Monoclonal antibodies e.g. Dupilimumab- inhibits IL-4 and il-13 signalling
- Acitretinoin

19
Q

What is the adaptive immune response in eczema?

A
  • Allergen is taken up by dendritic cells (langerhans)
  • Dendritic cells present antigens to t-cells in the lymph nodes
  • Th2 cells in lymph node secretes IL-4
  • IL-4 activates b-cells to change the class of antibodies to IgE which travel in the blood to mast cells
  • IgE is taken up by mast cells = release of pro-inflammatory mediators
20
Q

What is contact dermatitis?

A

Caused by substances in the home or workplace and usually occurs on the exposed area
2 types:
- Irritant- e.g. contact with acid, soaps, detergents
- Allergic- can be picked up in a patch test- mostly occupational causes

Common in wet work e.g. healthcare, hair dressers, labs, catering, cleaners

21
Q

What is the treatment of contact dermatitis?

A

Avoid allergens/irritants
Emollients- prevent water loss and cracking
Topical corticosteroids
Oral corticosteroids
Alitretinoin

22
Q

What are the symptoms of seborrheic dermatitis?

A
  • Rash with skin flakes
    itchiness, sore, redness
    greasy white or yellow scales
    in sebaceous skin zones e.g. face, scalp, chest, skin folds

Is caused by overgrowth of yeast

23
Q

What is cradle cap?

A

Seborrheic dermatitis in infants where thick, yellow waxy scales appear on hand
- also pink flaky patches on face, behind ears

24
Q

What is the treatment for seborrheic dermatitis?

A

INFANTS:
- Emollients
- Topical steroids with antifungal

ADULTS:
- Shampoos with ketoconazole
- Topical mild corticosteroids with salicylic acid
- Topical mild corticosteroids with anti-yeast creams/ointments e.g. clotrimazole, miconazole, nystatin
- severe cases = oral antifungals

25
Q

What is psoriasis?

A

A chronic autoimmune and inflammatory disease where skin cells are produced faster than they are shed

26
Q

Symptoms of psoriasis?

A

Itchy skin lesions
pink/white scales
Shapes and sizes vary
can split = painful

often triggered by external event e.g. strep infection, stress, skin injury, virus, corticosteroid withdrawal

27
Q

What are the different types of psoriasis (like an exam Q)?

A

PLAQUE PSORIASIS:
Is the most common type of psoriasis- can be alone or in combination with other types
Red, itchy sore patches with white/silver scales on surface
Clear margin of where places start and stop- can be seen and felt
Is red due to increased blood flow to the area- needed for the speed at which cells are being replicated
Occurs all over the body

SCALP PSORIASIS:
Thick scaly skin leading to dandruff-like flakes to fall
Is around the headlines, forehead, neck and ears
can lead to hair loss or thinning in severe cases
can make scalp feel itchy and tight
often flares up and then goes down

GUTTATE/TEARDROP PSORIASIS:
Bright pink/red looks like spots 9may be darker on darker skin)- like a widespread rash of small spots 9up to 1cm diameter)
widespread- especially on torso, back and limbs
some patients report the condition to be very itchy and sore, where others said it wasnt
often triggered by strep throat- people prone to throat infections may have repeat bouts of guttate psoriasis
common in children and young adults

PUSTULAR PSORIASIS
Small white/yellow fluid filled pustules form on top of red skin (skin is thick and flaky and so is prone to cracking- can make walking or using hands painful)
usually turn crusty and darkened once burst
common on palms of hands and soles of feet
Painful- required dermatologist treatment
- more common in women, those who smoke/have smoked. Also thought to be associated with diabetes, arthritis, thyroid disorders and coeliac

NAIL:
Up to 50% of patients with psoriasis develop it on nails- fingers or toes. Also around 80% of those with psoriatic arthritis have nail symptoms.
Often mistaken by a fungal infection
Causes nail discolouration, pitting (small dents), crumbling, cracking, splitting or detaching of nail from nail bed= onycholosis
People can be embarrassed by this

28
Q

What is different with the keratinocytes in psoriasis?

A

Keratinocytes usually take 3-4 weeks to work up from the basal layer of the epidermis up to be shred
BUT in Psoriasis, this takes only 3-4 days
This means the skin doesn’t have enough time to shed = build up of keratinocytes

29
Q

What is the pathophysiology process of psoriasis?

A
  • Often triggered by external trigger e.g. strep infection, virus, trauma
  • This stresses the keratinocytes
    and they produce inflammatory cytokines e.g. IL-1B IL-G TNF-A
  • This activates dendritic cells
  • Also as keratinocytes are stresses they break up and relied their DNA into the dermis. they also releases anti-microbial peptide LL-37
  • DNA released and the LL37 peptide combine to form a complex
  • The body doesnt recognise this complex and thinks theyre foreign = auto antigens = mounts an autoimmune response
  • These auto antigens are taken up by dendritic cells and are presented to the t-cells
  • T-cells are switched on = clonal expansion of th1 and th17 cells
  • produce cytokines- activates dendritic cells, chemokine = hyper proliferation of keratinocyte layer = can’t shed in time
30
Q

What are the treatments for psoriasis?

A

Topical:
Emollients
vitamin D derivatives- e.g. calcipitrol - inhibits proliferation and induces differentiation of keratinocytes = slow down excessive growth
Topical steroids e.g. eumovate, betnovate, dermovate
Dovobet= betamethasone and vit D
coal tar preps

SYSTEMIC;
Immunosuppressnts e.g. methotrexate, Ciclosporin
Vit a derivates e.g. acitretin
Apremilast
Anti-tnf, anti-il23, anti-il17 - more expensive so are last resorts

31
Q

What are the treatments of psoriatic arthritis?

A

Painkillers - NSAIDs, diclofenac, cox-2 inhibitors
corticosteroids
DMARDs e.g. leflunom9de
Biologics e.g. anti-tnf e.g. adalimumab, etanercept

32
Q

Wha treatments are used for warts?

A

Salicyclic acid containing creams or gels
- Cryosurgery- freezes with liquid nitrogen

33
Q

Discuss the three types of skin cancers:

A

BASAL CELL CARCINOMA:
- Local, slow-growing, unlikely to metastasise
- 4 x more common
- Caused by uv exposure= proliferation of basal keratinocytes
- common on head or neck
- use imaquimod cream

SQUAMOUS CELL CARCINOMA:
- Malignant and invasion and proliferate in epidermal keratinocytes
- 2nd most common skin cancer
- More common in men and elderly
- Caused by uv exposure - common in white skin that burns easily or can be caused by topical carcinogens e.g. arsenic, chronic immunosuppression
- good prognosis- 90% remission

MALIGNANT MELANOMA:
- Malignant proliferation of melanocytes (NOT keratinocytes)
- highest in Australia and New Zealand- high uv exposure
- mortality rate = 25%
-Limited treatment options

RISK FACTORS:
UV exposure
red and blonde hair
blue eyes
difficulty to tan
freckles
moles

SIGNS OF MELANOMA: ABCDE
(Changes to moles)
Asymmetry- not round
Border is irregular
Colour changes
Diameter >6mm
Evolving- crusting, bleeding, itching

Melanocytes in basal layer can turn into benign moles when they proliferate- if they grow out of control is can lead to asymmetrical moles
- Radial growth- through epidermis, then grow vertically and expand into the dermal layer
- this can lead to metastasis as they reach the blood vessels and so can spread

TREATMENT:
- Look at Breslow thickness- thickness of melanoma can predict 5-year survival rate
Early diagnosis
Surgery- removal of mole
Sentinal node biopsy- take biopsy of nearest lymph node to see if cells have spread
- chemotherapy- cytotoxic drugs e.g. paclitaxel, temozolamide
- targeted therapies- biologics e.g. ipilumamab, Anti-Brat

34
Q

How do you treat fungal infections e.g. athletes foot?

A

Topical imidazoles
or if severe, systemic anti fungal agents e.g. itraconazole

35
Q

What are the 5 targets for drugs in dermatology?

A
  • Surface of skin treatments e.g. antifungals, insect repellent, suncream
  • Startum corneum (epidermis)- keep moisture in e.g. emollients
  • Skin appendages e.g. sebum in sebaceous glands in acne is what is infected, antibiotics, anti-persperants- target sweat glands
  • Viable (lower epidermis)- anti-inflammatory, anaesthetics, anti-histamines
  • systemic- transdermal delivery
36
Q

How does transdermal delivery work?

A
  • Through stratum corneum, epidermis, dermis and into the vascular system
  • Penetration can be trans cellular (through the cells- if lipid based) or intracellular (between the cells)
37
Q

What are the advantages and disadvantages of transdermal delivery?

A

+ avoids first pass metabolism in the liver
+ consistent absorption site- no dependence on function or working GIT
+ Constant drug input rate - slow but constant release
+ can easily stop dose by removing patch
+ less frequent- patches can bw worn for 72 hours often

-is a complex process to generate
- max steady state flux- micrograms per hour- which isn’t much so drugs need to be potent

38
Q

Psoriasis aetiology?

A

2-3% of UK population
Affects men and women equally
Peeks in later teens-early 30s and then again between 50 and 60

Genetic predisposition- 1/4 of children with an infected parent develop, reason is unknown- several susceptibility loci
Trigger by outside event eg. strep throat, stress/injury to skin, virus e.g. HIV or HPV, corticosteroid withdrawel

39
Q

What are the types of wounds?

A

Superficial- damage to epithelium- heals rapidly due to regeneration of epithelial cells
Partial thickness- Involves the dermal layer and includes vascular damage
Full thickness- Involves subcutaneous fat layer and deeper, takes the longest to heal as new connective tissue is required.

40
Q

Discuss vitiligo and hyper and hypo pigmentation?

A

HYPO:
Vitiligo
decreased melanin production
Albinism
Infection/blisters
burns

HYPER:
Enhanced melanin production
Pregnancy
Addison’s disease
UV exposure

VITILIGO:
- Loss of skin colour in patches- discoloured areas often get bigger with time
- Can affect any part of the body- most common around eyes, nostrils, knees, elbows
- Melanocytes die or stop functioning = loss of melanin
- 95% cases develop before 40 years old
- no cure
- not contagious or life threatening

There are 3 types
- Focal- few spots in a single area
- Segmental- is unusual- patches on one side of the body
- Generalised - many patches all over- often symmetrical

Aetiology and pathogenesis:
- Have an autoimmune component- body makes autoantibodies to Tyrosine hydroxylase- this is involved in melanin synthesis
- increase in ROS production in mitochondria of affected cells- we don’t know the effect of this

  • 30% have family link
  • 15-24% have an autoimmune disease as well
  • immune system attacks its own melanocytes]
  • triggers = stress, skin damage, hormonal changes, chemical exposure (phenol), liver or renal disease