Basic Physiology Of Skin And Mechanisms Of Skin Disease

Front 1

Functions of skin [5]

Back 1

1. Thermo-regulation
2. Barrier function
3. Injury repair
4. Immunological defense
5. Psychosocial function

Front 2

Thermoregulation
- skin mechanisms [2 mechanisms]
- response to heat [2 stimulus, 2 responses]
- response to coldness [2 stimulus, 3 response]

Back 2

Skin: Radiator + insulator to preserve core temp 37°

Skin mechanisms
1. eccrine sweating (evaporative cooling):
*ecc gland densely populated in palm, sole, axilla
*ultrafiltrate of plasma-like fluid & hypotonic sweat (Ductal reabsorption of Na)
2. vessel tones (neurological control)

1. Response to heat, skin cooling in response to:
- Central heating (ext. source, int. source: ms exertion)
*evaporative cooling, vasodiltation
- Local heating (to Critical temp 45-50°)
*protein denatures → direct radiation, circulation

2. Response to coldness, skin heating in response to:
- Central hypothermia (heat loss to environment)
- Localized freezing injury
*responds by muscle exercise, shiver, vasoconstriction

Front 3

Barrier functions [5]

Back 3

1. Water/electrolytes: prevent loss
2. Toxic material; minimize irritation/harm
3. Microorganism: prevent infiltration
4. Allergens: avoid entrance
5. UV radiation: protect against it

Front 4

Clin exmples of skin failing to prevent dehydration and electrolyte loss? [2]
- what clinical sequelae are there [3]

Back 4

1. Defective skin barrier
- toxic epidermal necrolysis: full-thickness epidermal cell death
*extreme drug allergy (intrisc metabolism error so drug metabolite accumulates: phenolbarbitol, anticonvulsants, antibiotics)
- erythroderma (>90% skin covered by erythema)
*severely inflamed: psoriasis, eczema, drug eruption

2. Dehydration: lead to pre-renal failure, hypotension, hypernatremia

Front 5

clinical example where the skin fail to prevent entry of toxic material?

Back 5

Disorders of keratinization (defective SC: dead keratin envelope):
- less resistant to chemical penetration
- prone to bacterial & viral infection

1. Darier's disease (defective barrier function)
*lysis & defective formation: acantholysis + dyskeratosis (loss or splitting of epidermis)

2. epidermolytic hyperkeratosis

Front 6

Microorganisms skin protects against

Back 6

1. Bacterial (staphylo, strep, pseudomonas)
2. Viral (Herpes simplex, varicella-zoster)
3. Fungus (dermatophytes, candida)
4. Parasites (scabies)

Front 7

- name some allergens

Back 7

- house dust mites, feathers, pollen

Barrier dysfunction → entrance of allergens:

Front 8

Sequelae of failed protection against UV light
- skin disease against UV light

Back 8

1. Malignancy
- DNA damage → gene mutation
- Skin: SCC, BCC, melanoma
- Solid organs (liver kidney), haematological

2. Photo-aging (wrinkles, solar elastosis)

- Stratum corneum (reflect & scatter photons)
- Melanin (absorb photons): melanocyte → melanosomes → basal keratinocytes

Front 9

How does skin repair injury? [2]
- what types of injury are there [4]

Back 9

1. Epidermal → complete regeneration
2. Dermis → granulation (scarring)

- physical
- chemical
- thermal
- UV radiation

Front 10

Describe the skin's role in immune defense
- innate [7]
- adaptive [3]

Back 10

1. Innate immunity (lack immunological memory)
- Macrophage:
- PMN
- Eosinophil,
- Mast cell,
- NK T-cell,
- complements,
- anti-microbial peptides

2. Adaptive immunity
- has specificity & memory: strengthens memory on repeated encounters
- Ag presentation
- Antigen-presenting cell

Front 11

Features of macrophage [4]

Back 11

*mannose carbohydrate receptor

*phagocytic

*intracellular toxic molecules
- superoxide anion,
- hydroxyl radical,
- nitric oxide,
- anti-microbial cationic proteins

*process Ag to T/B cell

Front 12

Features of neutrophil [3]

Back 12

1. Phagocytosis → phagolysosomes
- oxygen-dependent mechanism
*respiratory burst
*hydrogen peroxide, hydroxyl radical, singlet oxygen
- oxygen-independent mechanism
*toxic cations
*toxic enzymes (myeloperoxidase, lysozyme)

2. Fc- receptor → antibodies tagged on pathogens

3. Activates complement receptors

Front 13

Features of eosinophils [4]

Back 13

- Parasitic infection
- Antigen-specific IgE antibodies
- weak phagocytic activity
- Release toxic cationic protein & peroxidase

Front 14

Features of basophils/mast cells
- difference between basophil and mast cell
- types of mast cell
- features [2]
- clinical disease [2]

Back 14

Basophil in peripheral blood, Mast cell in interstitial tissues

Types
1. Mucosal → trypsin
2. Connective tissue → trypsin, chymotrypsin

Features:
- high affinity for binding IgE
- specific Ag → bind cell-bound IgE (degranulation of histamine, serotonin, PG, LT)

Clinical disease
- urticaria
- angioedema

Front 15

Features of NK cell [2]

Back 15

1. Ab-dependent cellular cytotoxicity
- Fc receptor binds IgG

2. Secretion of perforin & granzymes
- perforin attacks cell membrane
- granzymes activate apoptosis cascade

Front 16

Features of Complements
- activated by [3]
- role of each complement

Back 16

- at least 20 serum glycoproteins

Activated by enzymatic amplying cascade
*Classical pathway (Ag-Ab complex)
*Alternative (polysaccharides, bacterial cell-wall)
*Lectin pathway (microbial carbohydrates)

- C3b: bind to surface of microbe → phagocytosis
- C3a, C4a, C5a: anaphylatoxin
- C5a: powerful attractant for neutrophils
- C5b, 6-9: MAC → pores in cell membrane (osmotic lysis)

Front 17

Features of anti-microbial peptides
- examples [2]
- clinical significance

Back 17

- secreted from epidermis
- anti-bacterial/viral/mycotic properties
e.g. Human B-defensin (HBD-1, 2, 3, 4), dermocidine

Psoriasis
- increased expression of HBD-2
- less bacterial infection in psoriasis px!

Front 18

Features of APC
- types of APC [3]
- pathway of APC
- interaction w. T-cell [2]

Back 18

APC
- Langerhan cells (epidermis)
- Dendritic cells (dermis)
- Macrophages

APC → drainage lymph nodes → lymphocytes

- interacts with T-cell receptors
1. CD4+ T-helper cell
*Th-1 (cellular immunity)
*Th-2 (humoral immunity)
2. APC + CD8+ cell → cytotoxic T-cell

Front 19

describe psychosocial function [2]
- dermatological disease [3]
- psychosocial implications [2]

Back 19

- attraction, beauty, youth, healthiness
- communication (Facial expression, hand/body gesture)

Dermatological disease
- Age (alopecia, photo-damage)
- Unhealthy (vitiligo, albinism)
- Infectious (psoriasis, eczema)

Psychosocial implications
- impact mood, occupation, relationship
- depression, suicidal ideation

Front 20

Common dermatological conditions [4]

Back 20

1. Atopic dermatitis (eczema)
2. Contact dermatitis
3. Cutaneous infection
4. Psoriasis

Front 21

describe Atopic dermatitis
- pathophysiology [4]
- clinical features [4]
- atopic tendency [3]
- epi [1]

Back 21

Pathophysiology:
1. Genetic
- filaggrin gene mutation
- lack of CERAMIDE (sphingolipid) which help integrity of barrier
- ↑transepidermal water loss

2. Immunological
- ↑serum total & allergen-specific IgE level
- Acute stage: Th-2 (humoral) response
- Chronic stage: Th-1 (cellular) response

3. Environmental
- Allergens: dust mites, feathers
- epicutaneous sensitization from break in skin barrier

4. Microbiology
- superantigen (Staph aureus)

Clinical features
- ill-defined erythematous scaling patches
- acute lesions: swelling, vesicles
- subacute lesions: discoid-shaped, weeping
- chronic lesions: lichenification

Atopic tendency (Asthma, allergic rhinitis, allergic conjunctivitis)

Epi: 10-20% developed countries

Front 22

Contact dermatitis
- types [2]
- clinical features [3]

Back 22

Types
1. Irritant
- more common
- exposure to irritant: often involve hands (housewife dermatitis)

2. Allergic
- Type 4 hypersensitivity reaction to allergens
- Common cause: topical herbal medication, cosmetics, eyedrops, topical antibiotics, nickel, cobalt

Clinical features
- usu well-defined border: confined to exposed area
- itchiness, erythema, scaling
- weeping, vesicles

Front 23

Cutaneous infections

Back 23

1. Bacterial (impetigo, erysepilas)
2. Viral (Herpes simplex virus, Varicella-zoster virus)
3. Fungus (dermatophytes, non-dermatophyte)
4. Parasitic (scabies, mite)

Front 24

Describe cutaneous bacterial infection
1. [5]
2. [5]

Back 24

1. Impetigo:
- Staphylococcus aureus
- more prevalent in children
- yellow/honey-coloured crusts peri-orally
- involvement of superficial epidermis
- Complications: bullous impetigo, staphylococcus scalded skin syndrome

2. Erysepilas
- Streptococcus pyogenes
- Well-defined painful patch on face
- involvement of dermis
- lymphatic spread (characteristically sluggish poor lymphatics)
- Complication: lymphedema, (rare) PSGN

Front 25

Describe cutaneous viral infection
1. [3]
2. [2]

Back 25

1. Herpes simplex virus
- vesicles → shallow erosions
- painful + recurrence is common
- Types: HSV-1 [herpes labialis] HSV-2 [genital herpes]

2. Varicella-zoster virus
- 1st episode chickenpox
- Recurrence: Herpes zoster (dermatomal, dissemination)

Front 26

Describe cutaneous fungal infection [2]

Back 26

1. Dermatophytes
- superficial fungal infection of skin
- stratum corneum/hair/nail
- trichophyton, epidermophyton, microsporum
- annular scaling patches w. advancing border

2. Non-dermatophyte [usu immunocompromised]
- candida, fusarium

Front 27

Describe cutaneous parasitic infection
- pathogen
- clinical features [3]
- pathophysiology

Back 27

sarcoptes scabiei

Clinical features
- severe itchiness
- discrete papules on limbs/trunk
- burrows, pustules

Pathophysiology
- HS to mites and droppings

Front 28

Psoriasis
- epi
- clinical features [5]
- pathophysiology

Back 28

Epi
- 0.3% population in HK, 2-3% in Caucasians

Clinical features
- well-demarcated erythematous scaling plaques
- extensor surfaces
- nail change: pitting, onycholysis
- scalp involvement
- Ax with arthropathy

Pathophysiology
1. Genetic
*HLA-Cw6, HLA-Bw16, PSORS1
*↑risk 40% if both parents have.

2. Immunological
*Th-1 response, cellular immunity
*upregulation of cytokines: IL1, IL6, TNF-a

3. Environmental
*Alcohol
*Drug: hydroxychloquine, terbinafine, lithium

4. Microbiological
*STreptococcus → guttae psoriasis in children
*HIV