Changes In Skin Colour Flashcards
Determinants of skin colour
Exogenous pigments
- introduced from outside (injection/ingestion)
Endogenous pigments
- produced within (melanin & breakdown of Hb)
Exogenous pigments
Carotenoderma
- consumption of large amounts of fruit/ veg high in beta-carotene eg: carrot, sweet potato & pumpkin
Tattoos
Ingestion of certain heavy metals eg: blue/black pigment at gum margin
Endogenous pigments
Melanin
- determinant = skin colour
- brown pigment produced by melanocytes (pigment producing cells)
- skin, choroid of eye, hair, mucous membranes & meninges
Pigments from haemaglobin breakdown
- bilirubin
- haemosiderin
Melanocytes
- dendritic cells in basal layer of epidermis
- intracytoplasmic organelles = melanosomes
- melanosomes = site of melanin synthesis, deposition & transportation to keratinocytes
- Epidermal melanin unit = association of 1 melanocyte with 30-40 surrounding keratinocytes to which transfers melanosomes
- darkly & lightly pigmented skin = same number of melanocytes
Dark = increased melanocytes activity, larger melanosomes - more melanin
Light = decreased melanocytes activity, smaller melanosomes - less melanin
Melanin bio synthetic pathway
- Tyrosine (amino acid) (=metabolized by enzyme tyrosinase to = DOPA, further metabolised form DOPAquinone
TYROSINASE (key regulatory enzyme = controls initial biochemical reactions , no = no melanin) - Dihydroxyphenylalanine
TYROSINASE - DOPAquinone
SERIES OF REACTIONS - melanin
Immediate pigmentary darkening
- follows exposure to UVA radiation
- Within minutes & fades over 20-30min
- oxidation of pre-existing melanin/ melanin precursors
Delayed tanning
- follow exposure to UVB & UVA radiation
- visible within 24-72hrs of exposure to UVB/UVA
- new pigment formation via increase in tyrosinase activity
Single exposure to UVR (cellular level)
- increase size of melanocytes observed
- increased tyrosinase activity
Repeated exposure to UVR (cellular level)
- increase number of melanosomes transferred to keratinocytes
- increased number of active melanocytes
Vitiligo
- acquired multifactorial disorder = autoimmune destruction of melanocytes
- depigmented macules & patches in localized/ generalized distribution
- areas of skin affected = absence of functional melanocytes
Vitiligo Pathogenesis
- multi factorial
- autoimmunity
- genetics
- oxidative stress
- environmental factors (exposure to chemicals)
- melanocytes detachment from BM
- neural hypothesis (nerve ending near pigment cells in epidermis, release cytotoxic neurochecmical mediators = melanocyte destruction)
- “convergence theory” (multiple mechanisms = melanocyte destruction & loss)
Autoimmunity (vitiligo Pathogenesis)
- associated autoimmune diseases: Hashimoto’s thyroiditis, Graves’ disease, TiDM, RA, Alopecia areata, Addison’s disease
- immune system = central role in Pathogenesis
- numerous activated cytotoxic T lymphocytes = perilesional area of vitiligo skin (mainly cytotoxic CD8 lymphocytes)
Autoimmunity process(vitiligo Pathogenesis)
- Genetic factors, environmental exposures
- Melanocytes stress
- Melanocyte stress signals sent via exosomes to APCs in skin
- Antigen presentation leads to T cell activation in lymph nodes & production of chemokines
- Recruitment of cytotoxic CD8 T cells which attack melanocytes
- Depigmented skin
Oxidative stress (vitiligo Pathogenesis)
- melanocytes from vitiligo patients have intrinsic defects = reduce capacity to manage cellular stress
- melanocytes respond to stress by releasing reactive oxygen species (ROS)
- production & accumulation of ROS triggers DNA damage & compromises cellular function
- oxidative stress tiggers immune response & recruitment of T cells = destruction of melanocytes
Examples of exogenous stressors
- UV radiation
- trauma
- cytotoxic compounds
Examples of endogenous stressor
- Melanin synthesis itself
- melanogenesis can be toxic to melanocytes itself = energy consuming process performed by melanocytes
Oculocutaneous Albinism (OCA)
- group of genetic disorders = hypopigmentation due to partial / total absence of melanin in skin, hair follicles & eyes
- multiple subtypes of OCA: OCA1 & OCA2 = 90% of cases
- almost always inherited in autosomal recessive manner
OCA Pathogenesis
- defect in melanin biosynthesis pathway
- mutations in genes that encode proteins involved in pathway
- normal number of melanocytes
- reduction in amount of melanin present in each melanosomes
OCA 2
- mutations in OCA2 gene encodes the P-protein
- “tyrosinase-positive” OCA (tyrosinase normal, p protein problem)
- P-protein is involved in the biogenesis of melanosomes & processing & transport of melanosomal proteins & pH-regulation that supports melanogenesis
- without p protein = melanin synthesis impaired
OCA1A
- OCA1 = TYR (gene mutation) * tyrosinase (gene product)
- severe gene mutation of TYR
- absent tyrosinase activity
- inability to produce pigment throughout life
- absent melanin in hair, skin, eyes
OCA1B
- milder gene mutation of TYR
- reduced tyrosinase activity
- low level of pigment production throughout life
- variable dilution in hair & skin pigment
Melasma
- acquired disorder of hyperpigmentation
= brown to grey macules & patched on sun exposed areas of skin - common, chronic & recurring disorder
- mostly commonly affects females with darker skin types
Risk factors & triggers of melasma
- multifactorial
- genetic predisposition (familial, 1st degreee relatives)
- sunlight exposure (UVR & visible light) NB
- skin phototype (skin phototype III-IV, medium pigmented)
- hormonal factors (pregnancy, oral contraceptives, hormone therapy, hyperestrogenic states)
- medications (photosentizing drugs, anti-epileptics eg: phenytoin)
Melasma Pathogenesis
- hyperpigmentation arises from hyper functional melanocytes that deposit an excess amount of melanin in dermis & epidemis
- normal number of melanocytes, larger number of melanosomes is affected skin
UVR plays NB role in Melasma pigmentation - induces production of alpha-melanocyte stimulating hormone
- directly stimulate melanocytes & increase melanin production
- chronic UVR = damage to BM of epidermis: penetration of melanocytes & melanin into dermis
Increased number of mast cells in skin - UVR triggers release of histamine from mast cells & histamine bind to H2 receptors in skin = activating tyrosinase pathway = melanogenesis
Chronic UV exposure increases vascularisation of Melasma lesions = pigmentation within skin