MSS31 Basic Physiology Of Skin And Mechanisms Of Skin Diseases Flashcards
1
Q
Important functions of skin
A
- Barrier
- loss of water, electrolytes
- toxic materials
- micro-organisms
- allergens
- UV radiation - Thermo-regulation
- Repair of injury
- Immunological defense
- Endocrine
- Psychosocial function
2
Q
Defective skin barrier
A
- ***Toxic epidermal necrolysis (90% caused by drug reactions)
- full-thickness epidermal cell death - ***Erythroderma (>90% skin covered by erythema)
- severely inflamed state
- e.g. psoriasis, eczema, drug eruption
Consequence:
- ***Dehydration and electrolyte loss
- -> pre-renal failure, hypotension, hypernatraemia
3
Q
Barrier to toxic material
A
Stratum corneum
- dead keratin envelop
- physical barrier
Defective SC:
- disorder of keratinization
- e.g. ***Darier’s disease, epidermolytic hyperkeratosis
- -> Less resistant to chemical penetration
- -> Recurrent bacterial infections
4
Q
Darier’s disease
A
- Autosomal dominant
- mutation in ***ATP2A2 gene
- prone to infections (bacterial/viral)
Histopathology:
- ***Suprabasal Acantholysis (loss of cohesion between keratinocytes)
- ***Dyskeratosis (abnormal keratinization occurring prematurely below stratum granulosum; normally in stratum corneum)
5
Q
Layers of skin
A
最出 –> 最入
- Epidermis:
1. Stratum corneum
2. Stratum lucidum
3. Stratum granulosum
4. Stratum spinosum
5. Stratum basale - Dermis
- Hypodermis
- Subcutaneous leyer
6
Q
Barrier to micro-organisms
A
Bacterial:
- Staphylococcus
- Streptococcus
- Pseudomonas
Viral:
- HSV
- Varicella-zoster
Fungus:
- Dermatophytes
- Candida
Parasites:
- Scabies
7
Q
Barrier to allergens
A
- Barrier dysfunction –> entrance of allergens e.g. house dust mites, feathers
-
Atopic dermatitis:
1. **Filaggrin gene mutation (key protein that facilitates terminal differentiation of the epidermis)
2. Lack of **ceramides (sphingolipids)
3. ↑ trans-epidermal water loss
4. Epi-cutaneous ***sensitization by allergens
8
Q
Barrier to UV light
A
Skin defense vs UV light
- Stratum corneum: reflect, scatter photons
- Melanin: absorb photons
- from ***melanosomes in melanocytes –> basal keratinocytes - Malignancies
- Skin: **SCC, **BCC, ***Melanoma
- Solid organs / haematological
- UV –> DNA damage –> gene mutation - Photo-aging
- wrinkles, solar elastosis
9
Q
Thermo-regulation
A
Skin mechanisms to regulate temperature:
- Skin as **radiator + **insulator
- Eccrine ***sweating (evaporative cooling)
- ***Vessel tones (neurological control)
Response to heat:
- Central heating
- external source
- internal (muscles exertion) - Local heating
- part of skin heated up to critical temp (45-50 oC)
- -> denaturation of protein
Elimination of heat:
- Central
- **Evaporative cooling
- **Vasodilatation - Local
- ***Direct radiation
- Circulation
Response to coldness:
- Central hypothermia (heat loss to environment)
- Localized freezing injury (e.g. frostbite)
Central heating:
- ***Muscle exercise (voluntary)
- ***Shivering (involuntary)
- ***Vasoconstriction
10
Q
Eccrine glands
A
Sweat glands
- millions in human body
- generalized distribution, densely populated in palms, soles, axillas
Secretory activities:
- ***Ultra-filtrate of plasma-like fluid
- ***Hypotonic sweat (ductal reabsorption of Na)
11
Q
Repair of injury
A
Types of injury
- Physical
- Chemical
- Thermal
- UV radiation
Healing:
- Epidermal –> complete regeneration
- Dermis –> granulation (scarring)
12
Q
***Immune defense
A
Innate:
- Primitive response
- Lack of immunological memory
- Effectors:
1. Macrophages, Eosinophils, Mast cell, NK T-cell
2. Complements
3. Anti-microbial peptide
Adaptive:
- Specificity
- Memory
- Strengthening of memory on repeated encounters
- Antigen presentation
- Effectors: APC
APC
- ***Langerhan cells (epidermis)
- ***Dendritic cells (dermis)
- ***Macrophages
APC –> lymph node drainage –> lymphocytes –> interact with T-cell receptors
- CD4 Th cells:
- Th-1: Cellular immunity
- Th-2: Humoral immunity - CD8 T-cell:
- Cytotoxic T-cell
13
Q
Macrophage
A
- Phagocytosis
- Carbohydrates receptor (***Mannose)
- ***Intracellular toxic molecules:
- -> Super-oxide anions, hydroxyl radicals, nitric oxides
- -> Anti-microbial cationic proteins
- Processed antigen to T-cell / B-cell
From HIS15:
- Reactive Oxygen Intermediate (ROIs) (majority)
- by Myeloperoxidase in Lysosome / Catalase from Peroxisomes
- Superoxide anion - Reactive Nitrogen Intermediate (RNIs)
- Nitric oxide (by nitric oxide synthase) - Other mediators
- Defensins, Lysozyme, Complements, Cytokines, Chemokines (e.g. IL-1, TNF, IFNγ)
End result:
- Bacterial killing
- Recruit + Activate additional immune cells
14
Q
Neutrophil
A
- Phagocytosis —> Phagolysosomes
- Oxygen-dependent mechanism:
—> respiratory burst
—> **H2O2, **hydroxyl radicals, singlet oxygens - Oxygen-independent mechanism:
—> toxic cations
—> toxic enzymes (***myeloperoxidase, lysozyme)
- Fc-receptor for Antibodies tagged on pathogens
- Complement receptors (Chemotaxis)
15
Q
Eosinophils
A
- ***Parasitic infection, Eczema, Drug allergies
- Weak phagocytic activity
- Antigen-specific ***IgE Ab
- Activated eosinophils
—> Release of toxic substances: **Cationic protein + **Peroxidase
(IgE Ab bound on eosinophil surface via Fc region
—> antigen bind to IgE Fab region
—> activate eosinophil
—> release of toxic Cationic protein + Peroxidase)
16
Q
***Basophils and Mast cells
A
Basophil: peripheral bloods
Mast cell: interstitial tissues
2 types of mast cells:
- Mucosal (produces trypsin)
- Connective tissue (produces trypsin, chymotrypsin)
- High affinity for IgE –> IgE bound on mast cells
- -> Specific antigens –> bind to mast cell-bound IgE
- -> degranulation
- -> **Histamine, **Prostaglandin, **Leukotriene, **Serotonin
Clinical presentation:
- Urticaria (hives)
- Angioedema (periorbital, hands etc.)
17
Q
Natural-killer cells
A
- Antibody-dependent cell-mediated cytotoxicity (**ADCC)
- Fc receptor that bind **IgG - Secretion of **Perforin + **Granzymes
- Perforin: attack cell membrane
- Granzymes: activate apoptosis cascade
18
Q
Complement
A
- > = 20 serum glycoprotein
- activated by enzymatic amplifying cascade
- Classical pathway (Ag-Ab complex)
- Alternative pathway (microbial antigen: polysaccharides, cell wall)
- Lectin pathway (microbial carbohydrates)
C3b (Opsonin):
- bind to surface of microbes
- Phagocytosis (C3b receptor)
C3a, C4a, C5a (Anaphylatoxins):
- ↑ vascular permeability
C5a:
- Chemotaxis: attract neutrophils
C5b+C6+C7+C8+C9:
- Membrane attack complex (MAC)
- -> make pores in cell membrane
- -> osmotic lysis
19
Q
Anti-microbial peptides
A
- secreted from ***epidermis
- e.g.:
1. **Human β-defensin (HBD): HBD 1-4
2. **Dermcidin - Anti-bacterial / viral / mycotic properties
- Psoriasis:
- -> ↑ expression of HBD-2
- -> less bacterial infection observed in psoriasis patients
20
Q
***Endocrinological function
A
- Vitamin D production
- 7-dehydrocholesterol
- -> cholecalciferol (D3) (skin)
- -> 25-hydroxyvitamin D (liver)
- -> 1,25-dihydroxyvitamin D (kidneys) - Glucocorticoid
- loosen intercellular connections and reduce epidermis effectiveness - Sex hormone
- ↑ epidermal thickness
- accelerate wound healing
- ↑ dendritic cell number protecting against cancer cells
21
Q
Psychosocial function
A
- Outermost organ
- Attraction (social, relationship)
- Sense of beauty, youth, healthiness
- Organ of communication
- -> facial expression
- -> hand / body gestures
Social perspective on dermatological diseases:
- Alopecia, photo-damage –> Aging
- Vitiligo (白蝕), albinism –> Unhealthy
- Psoriasis, eczema –> Infectious
Psychosocial implications
- Impact on mood, occupation, relationship
- Depression, suicidal ideation
22
Q
Common dermatological conditions
A
- Atopic dermatitis
- Contact dermatitis
- Cutaneous infection
- Psoriasis
23
Q
Atopic dermatitis
A
- Eczema
-
Clinical features:
1. **Ill-defined erythematous scaling **patches
2. Acute lesions: swelling, vesicles
3. Subacute lesions: discoid-shaped (盤狀), weeping
4. Chronic lesions: Lichenification
Atopic tendency:
- Asthma
- Allergic rhinitis
- Allergic conjunctivitis
Pathophysiology:
- Genetic
- ***filaggrin gene mutation (loss-of-function)
- -> ↑ trans-epidermal water loss - Environmental
- Allergens - Immunological
- ↑ serum total and allergen-specific **IgE level
- -> Acute stage: **Th-2 response (humoral immunity)
- -> Chronic stage: ***Th-1 response (cellular immunity) - Microbiological
- Super-antigens e.g. Staph. aureus
24
Q
Psoriasis
A
Clinical features:
- **Well-demarcated erythematous scaling **plaques
- ***Extensor surfaces
- Nail changes: pitting, onycholysis (painless detachment of the nail from the nail bed)
- Scalp involvement
- Association with arthropathy
Pathophysiology
- Genetic
- 1 parent with psoriasis: 14% risk
- both parents: 40% risk
- HLA-Cw6, HLA-Bw16, PSORS1 - Environmental
- alcohol
- drug: hydroxychloroquine, terbinafine, lithium - Immunological
- **Th-1 response (cellular immunity)
- Upregulation of **cytokines: IL-1, IL-6, TNFα, HBD-2 - Microbiological
- Streptococcus: guttate/eruptive psoriasis in children
- HIV
25
Q
Contact dermatitis
A
Irritant / Allergic
Clinical features:
- Usually ***well-defined border
- Confined to areas with exposure to culprits
- Itchiness, Erythema, Scaling
- Acute: weeping, vesicles
Irritant contact dermatitis
- more common
- exposure to irritant (e.g. chemicals)
- hand involvement (housewife dermatitis)
Allergic contact dermatitis
- hypersensitivity reaction to allergens
- ***Type IV hypersensitivity reaction (delayed type: 1-2 days after exposure)
- common causes:
- -> topical herbal medication
- -> cosmetics
- -> eyedrops, topical antibiotics
- -> nickel, cobalt
(Type IV hypersensitivity reaction:
1. Sensitisation phase:
APC (dendritic cells / Langerhans cells) —> CD4 T helper —> Th1
- Effector phase:
Sensitised Th1 —> IFNγ, IL-12
—> activate macrophage + CD8 T cell
—> ↑ Class II MHC, TNF receptor, oxygen radicals, Nitric oxide
Example:
Allergic contact dermatitis (poison ivy, latex)
Re-exposure —> rapid recruitment of **macrophage + CD8
—> **inflammatory infiltration + local oedema + erythema)
26
Q
Cutaneous infection
A
Bacterial
- Impetigo
- Staph. aureus / Strept. pyogenes
- children more prevalent
- **yellowish/honey-coloured crusts
- peri-oral area
- involvement of superficial **epidermis
- complications: Bullous impetigo, Staphylococcal Scalded Skin syndrome - Erysipelas
- Strept. pyogenes
- **well-defined **painful patches
- commonly found on face
- involvement of **dermis
- **lymphatic spread
- complications: Lymphedema, Post-streptococcal glomerulonephritis
Viral
- Herpes simplex virus (HSV)
- **vesicles –> shallow erosions
- painful, **recurrence common
- HSV-1: herpes labialis (cold sore)
- HSV-2: genital herpes - Varicella-zoster virus (VZV)
- 1st episode: chickenpox
- recurrence: Herpes Zoster (shingles: dermatomal dissemination)
Fungus
- Dermatophytes / Ringworm
- superficial fungal infection of skin
- Stratum corneum / Hair / Nail (keratin layer —> Dermatophytes are keratinolytic)
- **Trichophyton / **Epidermophyton / **Microsporum
- Clinical features: **Annular scaling patches with ***advancing border - Non-dermatophyte
- Candida, Fusarium
Parasitic
- Scabies infestation
- **Sarcoptes Scabiei
- Clinical features:
- -> Severe itchiness
- -> Discrete papules on limb/trunk
- -> **Burrows, pustules
- Pathophysiology:
- -> Hypersensitivity to mites and their droppings
