Skin and Eye Flashcards
final exam
why do we have skin?
- mechanical support
- neurosensory
- environmental barrier
- many physiological roles –
- thermal regulation
- metabolism
- regulate blood flow, fur and hair, sweat
- electrolyte regulation
- immune function
- hormone function
layers of the skin
- epidermis
- dermis
- hypodermis
what is found throughout the layers of the skin?
- hair follicles
- sweat glands
- innervation
- vascular supply
which cells make up the epidermis?
- langerhans cells
- melanocytes
- merkel cells
- keratinocytes
what is the top layer of the epidermis
stratum corneum
function of Langerhan cells
part of the immune system (take up and process antigens) – antigen presenting cells
function of melanocytes
make pigment and insert into keratinocytes
function of Merkel cells
respond to touch (mechanosensors)
what makes up the stratum corneum?
- dead keratinocytes called corneocytes
- held by desmosomes and lipids
lifetime +path of keratinocytes
- last 4 weeks
- keratinocytes make their way up to the top of epidermis
role of stratum corneum
barrier that conserves moisture
why does the biology of the epidermis matter for toxicology?
Thickness varies in different parts of the body (important for dermal absorption):
- palms of hands/soles of feet have thick stratum corneum to resist abrasion
- thinnest region is behind the ear (drugs readily absorbed)
- thin skin has many hair follicles
Children have thinner skin:
- vulnerable to damage and absorption of molecules
role/function of the dermis
- thermoregulation
- supply the avascular epidermis with nutrients
- secrete substances that give support and elasticity of the skin.
what makes up the dermis? what do they do?
fibroblasts which are responsible for secreting collogen, elastin, and ground substances.
They are also import for wound healing.
how can toxins and toxicants pass through the skin?
- intracellular (through tight sections between cells)
- via glands or hair
- transcellular (when lipophilic)
which type of compound can go through the skin?
small, lipophilic molecules (e.g. toluene, benzene, carbon tetrachloride)
what are reasons why the barrier (skin) can be impaired?
- disease
- abrasion
- elevated water content
examples of solvents?
toluene and turpentine
where is toluene used?
paint thinner and permanent markers
properties of industrial solvents, what does this tell us?
small, lipophilic, so can be absorbed through skin
what are effects of some industrial solvents?
- cause local irritation
- dissolve the lipid barrier (damages skin and makes it more susceptible)
- systemically absorbed (can have effect on nervous system)
how is nicotine from a patch absorbed? what are the pharmacokinetics?
- Slowly and steadily absorbed through skin
- Gets directly into blood stream (no first pass)
- but, some first-pass effect in skin since has some P450s, and phase 2 enzymes.
what is dermatitis?
inflammation of the skin
what is contact dermitis?
inflammation of the skin through contact with toxicants
what are the main types of contact dermititis?
- irritant
- allergic
what is irritant dermatitis?
- Inflammatory response
- No single mechanism of action – many cytokines
- Intensity related to dose
- Great individual variability
types of chronic irritation
- chronic irritation
- acute irritation
what is chronic irritation? what causes it?
- irritant dermatitis from repeated exposure
- from mild irritants such as soaps, detergents, solvents
what is acute irritation? what causes it?
- also called 2nd-degree chemical burn
- substantially disrupts the cornified layer
- strong acids, alkalies, oxidizing & reducing agents
what does wet cement cause? why?
acute irritation
- is very alkaline (pH 12-14)
- sand and small particles irritate the skin
- Can’t feel burn from basic substances right away
what is allergic dermatitis? when does it occur?
- delayed (T-cell mediated) hypersensitive reaction
- occurs when a molecule (called hapten) generates an allergic reaction
mechanism of allergic dermatitis
- hapten penetrate the lipid barrier and become attached to carrier proteins
- hapten + carrier protein = antigen
- antigens are processed by Langerhans cells
- Langerhans cells present antigen to T cells in lymph nodes
- T cells become “activated” and proliferate
- over a 1–3 week period, activated T cells are generated and enter the circulation
- then, when there is a 2nd contact, activated T cells induce inflammatory reaction (limited to area of 2nd exposure)
what causes allergic dermatitis?
- plants such as poison oak, poison ivy, henna
- metals such as nickel
- rubber from things such as gloves
- glue (e.g. band-aids)
- drugs (e.g. polysporin/neosporin)
differences between irritant and contact dermatitis
irritant:
- more common
- from local toxic effect
- affects everyone; no sensitization required
- reaction soon after
- repeated exposure is required
- lesion restricted to area of exposure
- burning
allergic:
- less common
- delayed type hypersensitivity reaction
- sensitization required
- delayed reaction (hrs to days)
- small amount of allergen is enough
- localized but may be more diffuse
- no burning
Exposure from light comes from what?
- sun
- indoor tanning
- UVA (deeper) and UVB (UVC doesn’t reach us)
why is it that UVC doesn’t reach us?
has a lower wavelength, so More energy = more reactions, causing more intense effects = don’t penetrate through atmosphere or skin as deep
when can phototoxicity occur? what type of reaction occurs? what can cause it?
when certain compounds react with sunlight and damage skin
- not an immunologic response
- meaning no prior exposure to the photosensitizing agent is required
- can be due to tattoo ink, drugs (antibiotics, Chlorpromazine), and plants (carrot, citrus, legume)
which compound in plants is the most common reason for phototoxicity?
furanocoumarins (i.e. psoralen)
mechanism of furanocoumarins
- activated by long-wavelength UVA light
- interacts with DNA covalently, causing DNA damage
what is a Photocarcinogen?
substance which causes cancer when an organism is exposed to it + light
how do photocarcinogens get activated (by which mechanism)?
- after illumination, compound transitions to an excited state
- compound becomes more chemically reactive
- light can also cleave photocarcinogens, resulting in free radicals
what is phtoallergy?
Photocontact dermatitis occurs upon exposure to sunlight:
- compound absorbs UV light, converted to hapten, type IV hypersensitivity reaction
what can cause a photoallergic response?
- antibacterial soaps (hexachlorophene)
- drugs (antihistamines such as diphenhydramine)
- ingredients in cosmetics (musk, sandalwood oil, ..)
what is Urticaria? what happens?
- means hives
- type I or “anaphylactic” reaction, mediated by release of IgE and release of histamine
- causes increases the permeability of capillaries to white blood cells/proteins (to engage pathogens in infected tissues)
symptoms of Urticaria
- wheals (red bumps)
- itching
- hayfever
- bronchial asthma
what can cause urticaria?
-plants
-latex
-antibiotics
How do we determine sensitization using animals and cells?
- Guinea pig maximization test
- Mouse local lymph node assay (LLNA)
- in vitro cell culture (Keratinocytes, and Langerhans)
- in vitro skin irritancy test (EpiSkin)
which part of the eye is more susceptible to toxicant injury?
anterior part of the eye (which faces out to world) – includes the Cornea, conjunctive and eyelids
what is the main effect of compounds that are toxic to the retina, optic nerve, and visual cortex?
visual impairment
which compounds can lead to visual impairment?
lead, methanol, methyl mercury
does the eye contain metabolizing enzymes?
yes, both phase 1 and 2
what are some ways to test toxicity in the eye?
- used to use rabbits
- now use isolated chicken eye
- bovine corneal opacity permeability (normal is not very opaque)
- Short Time Exposure In Vitro Test
explain the Short Time Exposure In Vitro Test to look at eye toxicity.
Method for Identifying
i) Chemicals Inducing Serious Eye Damage
ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage
Test consists of:
- monolayer of Statens Seruminstitut
Rabbit Cornea (SIRC) cells
- 96-well plate MTT assay
what are some household hazards?
- paint thinner, cement
- plants, UV light, insecticides, weeds, bees
- cleaning products, bleach, medicine, Neosporin, band aids, antibacterial soaps
- latex, oven cleaner
- cosmetics, houseplant, nickel
