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MSS > MSS31 Basic Physiology Of Skin And Mechanisms Of Skin Diseases > Flashcards

MSS31 Basic Physiology Of Skin And Mechanisms Of Skin Diseases Flashcards

1
Q

Important functions of skin

A
  1. Barrier
    - loss of water, electrolytes
    - toxic materials
    - micro-organisms
    - allergens
    - UV radiation
  2. Thermo-regulation
  3. Repair of injury
  4. Immunological defense
  5. Endocrine
  6. Psychosocial function
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2
Q

Defective skin barrier

A
  1. ***Toxic epidermal necrolysis (90% caused by drug reactions)
    - full-thickness epidermal cell death
  2. ***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
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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
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4
Q

Darier’s disease

A
  • Autosomal dominant
  • mutation in ***ATP2A2 gene
  • prone to infections (bacterial/viral)

Histopathology:

  1. ***Suprabasal Acantholysis (loss of cohesion between keratinocytes)
  2. ***Dyskeratosis (abnormal keratinization occurring prematurely below stratum granulosum; normally in stratum corneum)
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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
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6
Q

Barrier to micro-organisms

A

Bacterial:

  • Staphylococcus
  • Streptococcus
  • Pseudomonas

Viral:

  • HSV
  • Varicella-zoster

Fungus:

  • Dermatophytes
  • Candida

Parasites:
- Scabies

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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
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8
Q

Barrier to UV light

A

Skin defense vs UV light

  1. Stratum corneum: reflect, scatter photons
  2. Melanin: absorb photons
    - from ***melanosomes in melanocytes –> basal keratinocytes
  3. Malignancies
    - Skin: **SCC, **BCC, ***Melanoma
    - Solid organs / haematological
    - UV –> DNA damage –> gene mutation
  4. Photo-aging
    - wrinkles, solar elastosis
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9
Q

Thermo-regulation

A

Skin mechanisms to regulate temperature:

  1. Skin as **radiator + **insulator
  2. Eccrine ***sweating (evaporative cooling)
  3. ***Vessel tones (neurological control)

Response to heat:

  1. Central heating
    - external source
    - internal (muscles exertion)
  2. Local heating
    - part of skin heated up to critical temp (45-50 oC)
    - -> denaturation of protein

Elimination of heat:

  1. Central
    - **Evaporative cooling
    - **    Vasodilatation
  2. Local
    - ***Direct radiation
    - Circulation

Response to coldness:

  1. Central hypothermia (heat loss to environment)
  2. Localized freezing injury (e.g. frostbite)

Central heating:

  1. ***Muscle exercise (voluntary)
  2. ***Shivering (involuntary)
  3. ***Vasoconstriction
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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)
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11
Q

Repair of injury

A

Types of injury

  1. Physical
  2. Chemical
  3. Thermal
  4. UV radiation

Healing:

  1. Epidermal –> complete regeneration
  2. Dermis –> granulation (scarring)
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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

  1. CD4 Th cells:
    - Th-1: Cellular immunity
    - Th-2: Humoral immunity
  2. CD8 T-cell:
    - Cytotoxic T-cell
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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:

  1. Reactive Oxygen Intermediate (ROIs) (majority)
    - by Myeloperoxidase in Lysosome / Catalase from Peroxisomes
    - Superoxide anion
  2. Reactive Nitrogen Intermediate (RNIs)
    - Nitric oxide (by nitric oxide synthase)
  3. Other mediators
    - Defensins, Lysozyme, Complements, Cytokines, Chemokines (e.g. IL-1, TNF, IFNγ)

End result:

  • Bacterial killing
  • Recruit + Activate additional immune cells
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14
Q

Neutrophil

A
  1. Phagocytosis —> Phagolysosomes
  • Oxygen-dependent mechanism:
    —> respiratory burst
    —> **H2O2, **hydroxyl radicals, singlet oxygens
  • Oxygen-independent mechanism:
    —> toxic cations
    —> toxic enzymes (***myeloperoxidase, lysozyme)
  1. Fc-receptor for Antibodies tagged on pathogens
  2. Complement receptors (Chemotaxis)
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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)

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16
Q

***Basophils and Mast cells

A

Basophil: peripheral bloods
Mast cell: interstitial tissues

2 types of mast cells:

  1. Mucosal (produces trypsin)
  2. 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
  1. Antibody-dependent cell-mediated cytotoxicity (**ADCC)
    - Fc receptor that bind **    IgG
  2. Secretion of **Perforin + **Granzymes
    - Perforin: attack cell membrane
    - Granzymes: activate apoptosis cascade
18
Q

Complement

A
  • > = 20 serum glycoprotein
  • activated by enzymatic amplifying cascade
  1. Classical pathway (Ag-Ab complex)
  2. Alternative pathway (microbial antigen: polysaccharides, cell wall)
  3. 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
  1. Vitamin D production
    - 7-dehydrocholesterol
    - -> cholecalciferol (D3) (skin)
    - -> 25-hydroxyvitamin D (liver)
    - -> 1,25-dihydroxyvitamin D (kidneys)
  2. Glucocorticoid
    - loosen intercellular connections and reduce epidermis effectiveness
  3. 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
  1. Atopic dermatitis
  2. Contact dermatitis
  3. Cutaneous infection
  4. 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:

  1. Genetic
    - ***filaggrin gene mutation (loss-of-function)
    - -> ↑ trans-epidermal water loss
  2. Environmental
    - Allergens
  3. Immunological
    - ↑ serum total and allergen-specific **IgE level
    - -> Acute stage: **    Th-2 response (humoral immunity)
    - -> Chronic stage: ***Th-1 response (cellular immunity)
  4. Microbiological
    - Super-antigens e.g. Staph. aureus
24
Q

Psoriasis

A

Clinical features:

  1. **Well-demarcated erythematous scaling **plaques
  2. ***Extensor surfaces
  3. Nail changes: pitting, onycholysis (painless detachment of the nail from the nail bed)
  4. Scalp involvement
  5. Association with arthropathy

Pathophysiology

  1. Genetic
    - 1 parent with psoriasis: 14% risk
    - both parents: 40% risk
    - HLA-Cw6, HLA-Bw16, PSORS1
  2. Environmental
    - alcohol
    - drug: hydroxychloroquine, terbinafine, lithium
  3. Immunological
    - **Th-1 response (cellular immunity)
    - Upregulation of **    cytokines: IL-1, IL-6, TNFα, HBD-2
  4. Microbiological
    - Streptococcus: guttate/eruptive psoriasis in children
    - HIV
25
Q

Contact dermatitis

A

Irritant / Allergic

Clinical features:

  1. Usually ***well-defined border
  2. Confined to areas with exposure to culprits
  3. Itchiness, Erythema, Scaling
  4. 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

  1. 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

  1. 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
  2. Erysipelas
    - Strept. pyogenes
    - **well-defined **painful patches
    - commonly found on face
    - involvement of **dermis
    - **    lymphatic spread
    - complications: Lymphedema, Post-streptococcal glomerulonephritis

Viral

  1. Herpes simplex virus (HSV)
    - **vesicles –> shallow erosions
    - painful, **    recurrence common
    - HSV-1: herpes labialis (cold sore)
    - HSV-2: genital herpes
  2. Varicella-zoster virus (VZV)
    - 1st episode: chickenpox
    - recurrence: Herpes Zoster (shingles: dermatomal dissemination)

Fungus

  1. 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
  2. Non-dermatophyte
    - Candida, Fusarium

Parasitic

  1. Scabies infestation
    - **Sarcoptes Scabiei
    - Clinical features:
    - -> Severe itchiness
    - -> Discrete papules on limb/trunk
    - -> **    Burrows, pustules
    - Pathophysiology:
    - -> Hypersensitivity to mites and their droppings

MSS (32 decks)

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