Effect of environment of skin

The Skin: Vital Organ

• The skin is the interface between the body and the external environment, constantly exposed to physical, chemical, and biological stresses

• It is a vital organ essential for survival

Consequences of extensive skin damage (epidermal ± dermal)

• Can occur in severe burns or rare drug reactions

• May be fatal due to:
  

  • Dehydration and shock

  • Infection

  • Heat loss and hypothermia (or hyperthermia from impaired thermoregulation)

  • Protein loss, electrolyte imbalance

  • High-output cardiac failure

  • Renal failure

Toxic epidermal necrolysis (TEN)

• Rare, severe adverse drug reaction

• Characterised by detachment of the epidermis

• Often preceded by flu-like symptoms

• Rapid development of painful erythematous rash and desquamation of skin and mucous membranes

• High mortality, highlighting the critical protective role of skin

Environmental Insults

• The skin protects the body from multiple external challenges while maintaining homeostasis and thermoregulation

• Major environmental insults include:
  

  • UV radiation and irradiation

  • Microbes and ectoparasites

  • Physical trauma (burns, friction, pressure)

  • Chemical irritants

  • Allergens

• Damage or breach of the skin barrier compromises protection and disrupts normal body function

Protective features of Skin

• Prevents drying: waterproof epidermis plus sebum from sebaceous glands

• Resists friction and impact:
  

  • Thick, regenerating, keratinised epidermis

  • Nails

  • Basement membrane anchoring epidermis to dermis with a wavy interface to resist shear

  • Strong collagen fibres in the dermis arranged in multiple directions

• Heat regulation: sweating and vasodilation

• Cold protection: subcutaneous fat, adjustable blood supply, and hair (especially on the head)

• Protection from burns and injury: thick, regenerating epidermis

• Protection from radiation/sunlight: thick epidermis and melanin

• Defense against infection: impervious epidermal barrier and resident immune cells

Normal Skin Adaptations to the Environment

• Temperature regulation
  

  • Sweating and vasodilation in heat

  • Vasoconstriction in cold

  • Rapid response (minutes)

• Hyperkeratosis (callus formation)
  

  • Thickening of the stratum corneum in response to repeated rubbing or pressure (e.g. feet, fingers)

  • Can also occur mildly after UV exposure

  • Slow response (weeks)

• Tanning
  

  • Increased melanin production by melanocytes after UV exposure

  • Protective response to radiation

  • Slow response (days)

Thermoregulation by blood supply

• Skin temperature is regulated by arteriovenous (AV) shunts in the dermis

• AV shunts connect arterioles and venules and are abundant in the dermis

• They respond to skin thermoreceptors detecting heat or cold

• Shunts open → increased blood flow to the superficial vascular plexus in the papillary dermis
  

  • More heat loss

  • Skin appears redder

• Shunts close → reduced superficial blood flow
  

  • Heat conserved

  • Skin appears pale or blue

• Facial blood flow can also change due to emotional or sympathetic nervous system activity (blushing)

• Prolonged shunt closure can cause tissue damage, e.g. frostbit

UV protection: Epidermal melanin

• Skin colour
  

  • Determined mainly by melanin (darker skin) and haemoglobin (lighter skin)

  • Large normal genetic variation in melanin production (many genes involved)

• Role of melanin
  

  • Absorbs UV radiation and protects DNA from damage

  • Reduces risk of skin cancer

  • Darker skin has significantly lower skin cancer incidence than lighter skin

• Melanocytes
  

  • Located in the epidermis

  • Produce melanin in melanosomes

  • Transfer melanosomes mainly to basal keratinocytes

  • Keratinocytes position melanin over the nucleus to shield DNA

• Tanning
  

  • UV exposure increases melanocyte activity

  • More melanin synthesis and transfer to keratinocytes

  • Provides partial protection against further UV damage

  • Accompanied by epidermal thickening, adding extra protection

• Mechanism of suntanning
  

  • UV causes DNA damage signalling in basal keratinocytes

  • Keratinocytes release MSH (melanocyte-stimulating hormone)

  • MSH binds MC1R on melanocytes

  • Activates cAMP signalling → increased transcription

  • Results in increased melanin synthesis, transfer, and melanocyte activity

• Melanin synthesis pathway
  

  • Tyrosine → L-DOPA → DOPAquinone (via tyrosinase)

  • Produces:
    

    • Eumelanin (brown–black)

    • Pheomelanin (yellow–red)

Protection against microorganisms

• Langerhans cells are key immune cells in the epidermis

• Located mainly in the non-basal layers of the skin

• Are dendritic cells

• Function as antigen-presenting cells, similar to macrophages

• Form an immune surveillance network within the epidermis

• Act as part of the skin’s immune defence against microorganisms

Abnormal effects of the environment: Damage by ‘insults’

• Environmental insults include friction/scratching, ultraviolet radiation, burns, irritants, allergens, and microbes

• Chronic or excessive exposure leads to structural damage, inflammation, abnormal growth, and malignancy

Friction and scratching

• Can cause lichenification: a severe form of hyperkeratosis

• Skin becomes thickened, rough, and accentuated in skin markings due to repeated rubbing or scratching

Ultraviolet (UV) radiation effects

• UVA (longer wavelength): penetrates deeper, contributes to photoaging and wrinkles

• UVB: causes direct DNA damage, sunburn, and increases cancer risk

• UVC is filtered out by the ozone layer

Sunburn

• A radiation burn caused by UV exposure

• Leads to inflammation, blistering, and keratinocyte cell death due to DNA damage

• History of sunburn significantly increases skin cancer risk

• Use of UV sunbeds before age 35 markedly increases melanoma risk

Polymorphic light eruption

• Immune-mediated “sun allergy” triggered by UV exposure

• Causes itchy red papules or plaques on sun-exposed skin

Photoaging (solar elastosis)

• Chronic UV exposure damages elastic fibres in the dermis

• Results in wrinkles, loss of skin elasticity, and leathery appearance

Pigmentary changes related to UV

• Freckles (ephelides):

  • Genetically influenced, linked to MC1R variants and fair/red hair

  • Increased melanin production without increased melanocyte number

  • Appear on sun-exposed skin

• Naevi (moles):

  • Benign proliferation of melanocytes

  • Numerous or large naevi increase melanoma risk

Solar lentigos (liver/age spots)

• Benign, flat brown lesions caused by chronic UV exposure

• Age-related and found on sun-exposed areas

• Due to increased melanin, not increased melanocyte number

Solar keratoses (actinic keratoses)

• UV-induced dysplastic growth of keratinocytes

• Rough, scaly premalignant lesions on sun-exposed skin

• Can progress to squamous cell carcinoma

Skin cancer (UV-related)

• Results from cumulative UV-induced DNA damage

• Two major categories:
  

  • Melanoma: arises from melanocytes, least common but most dangerous

  • Non-melanoma skin cancers (keratinocyte-derived, more common):
    

    • Squamous cell carcinoma

    • Basal cell carcinoma (most common, least aggressive)

UV – beneficial effects

• UV exposure is required for vitamin D₃ synthesis in the skin
  

  • ~15 minutes of summer sunlight on face and arms is usually sufficient for light skin

  • Longer exposure is needed for darker skin

  • Vitamin D can also be obtained via supplements

• Therapeutic UV (phototherapy) is used clinically to treat certain skin conditions
  

  • Examples: vitiligo and psoriasis

Burns

• Superficial burn (1st degree)
  

  • Damage limited to the epidermis

  • Epidermis destroyed only

  • Heals without scarring

• Partial thickness burn (2nd degree)
  

  • Damage to epidermis + part of dermis

  • Sebaceous glands may remain intact

  • May blister

  • May heal without scarring if dermal structures survive

• Full thickness burn (3rd degree)
  

  • Destruction of epidermis, dermis, and deeper tissues

  • Loss of skin appendages and nerve endings

  • Results in scarring

  • Often associated with loss of pinprick sensation initially

Irritants: Irritant Contact Dermatitis

• Caused by excessive exposure to an irritating substance (dose-dependent, not immune-mediated)

• Sensitivity varies between individuals

• Condition often improves by reducing exposure rather than complete avoidance

• Typical features include redness, itching, swelling, blistering, and/or scaling

Allergens: Allergen Contact Dermatitis

• Immune-mediated allergy to a substance contacting the skin

• Very small amounts of allergen can trigger a reaction

• Sensitivity varies widely; can develop after short or prolonged exposure

• Symptoms include redness, itching, swelling, blistering, and/or weeping

• Management: strict avoidance of the allergen

Key comparison & mechanism (allergens vs irritants)

• Irritant contact dermatitis:
  

  • Common

  • Dose-dependent, non-immune

• Allergic contact dermatitis:
  

  • Relatively uncommon (e.g. nickel)

  • Requires sensitisation first: Langerhans cells present antigen to lymphocytes

  • Delayed (type IV) hypersensitivity on re-exposure via memory T cells

Microbes(Fungi, Bacteria, Viruses)

• Paronychia
  

  • Infection of the nail fold

  • Can be bacterial or fungal

  • Often associated with damaged skin around the nail

• Fungal – Tinea capitis
  

  • Scalp ringworm

  • Patchy hair loss with scaling

  • Caused by dermatophyte fungi

• Bacterial – Impetigo
  

  • Superficial bacterial skin infection

  • Crusting lesions, commonly in children

  • Often caused by Staphylococcus aureus or Streptococcus

• Bacterial – Cellulitis
  

  • Deeper skin infection (dermis/subcutis)

  • Red, hot, swollen, painful skin

  • Commonly caused by Streptococcus

  • Enters via breaks in the epidermis

• Viral – Human papillomavirus (HPV)
  

  • Causes warts

  • Hyperkeratotic, rough surface lesions

Key infection principles

• Portal of entry

  • Microbes enter through breaches in the epidermis

• Impaired immunity increases risk

  • Examples: HIV, widespread viral warts

  • Eczema herpeticum: herpes simplex virus infecting eczematous skin