L14. Skin, Eye, & Household Hazards Flashcards
Why is skin an important organ to talk about in terms of toxicology?
- Skin is 6% of your body weight -> really important mechanism of exposure.
- Occupational skin diseases are the 2nd most common type of occupational disease.
- 13 million U.S. workers are exposed to chemicals that can be absorbed through skin.
- We are exposed to many household elements through our skin.
Why do we have skin?
- Mechanical support (keeps all organs in)
- Neurosensory reception
- Environmental barrier
- Many physiological roles
What are some examples of physiological roles of the skin?
- Thermal regulation
- Regulation of blood flow, fur and hair, sweat
- Metabolism
- Electrolyte regulation
- Immune function
- Hormone function
- etc
What are the 3 primary layers of the skin? What are found throughout the layers of the skin?
3 primary layers:
- Epidermis (outer layer & barrier)
- Dermis
- Hypodermis
Throughout the layers of skin, there are:
- hair follicles
- sweat glands
- innervation & circulation
- vascular supply
What are difference cell types found in the epidermis? Describe their purpose.
- Langerhans cells:
- part of the immune system (take up and process antigens) - Melanocytes:
- make pigment to insert into keratinocytes. - Merkel cells:
- respond to touch (i.e. mechanosensors) ->make you feel pressure
What is the top layer of the epidermis called? What’s it made of? Describe it.
Stratum corneum • superficial (top) layer of epidermis • made of dead keratinocytes called corneocytes • we continually shed this layer • keratinocyte lifetime = 4 weeks -> every 4 weeks there is a new layer • keratinocytes make their way up to the top of epidermis as they grow and divide and eventually die.
What makes corneocytes a good barrier?
Corneocytes are connected with desmosomes (really strong cell-cell adhesion proteins) very tightly. This makes it a good barrier. It also allows us to keep our moisture in. They are also held by lipids.
Why does the biology of the epidermis matter for toxicology?
Thickness varies in different parts of the body:
• 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
Why is the dermis important?
- Thermoregulation
- It supplies the avascular epidermis with nutrients. Since the dermis is innervated by vasculature, if things get into the dermis they will get all over.
- The dermis contains mostly fibroblasts which are responsible for secreting collagen, elastin, and ground substance that give the support and elasticity of the skin.
- Fibroblasts are also important for wound healing.
What type of cells are present in the epidermis and are part of the immune system? A. Merkel cells B. Corneocytes C. Langerhans D. Stratum coreum E. Desmosomes
C. Langerhans
How can toxicants be absorbed through your skin?
- Intercellularly: small or non-polar molecules can pass in between the cells or other molecules can pass through if the barrier gets damaged.
- Transcellularly: molecules that are lipid soluble
- Via hair or glands
What types of molecules can get through the stratum corneum? Give some examples.
Most compounds cannot get through the stratum corneum. BUT! Small, lipophilic molecules can enter! Examples include: Toluene; benzene; carbon tetrachloride.
What can cause an impaired stratum corneum barrier?
- disease
- abrasion
- elevated water content (i.e. swimming) -> Our skin is approx. 7% hydrated, but if it gets more hydrated it can allow slightly more polar molecules to go through (like 5X more).
Why are solvents dangerous? What are some examples?
Many industrial solvents are small, lipophilic molecules (and get absorbed!)
Some are particular dangerous because they:
• Cause local irritation
• Dissolve the lipid barrier→damaging the skin and making us more susceptible
• Systemically absorbed (i.e. effect on nervous system)
Examples:
- Toluene (used in paint thinner and permanent markers)
- turpentine (used for wood polish or in some waxes - found at hardware store)
Describe how the nicotine patch works.
- The nicotine is slowly and steadily absorbed through skin (make sure to out on specific areas of skin that have good absorption. Ex: stratum corneum on sole of the foot is way too thick)
- Gets directly into blood stream
- No first pass effect through liver (also known as first pass metabolism)
Note: There is a first pass effect from skin!
- Phase I several cytochrome P450s
- Phase I flavin monooxygenase
- Some Phase II metabolism as well
What are some skin disorders caused by exposure?
- Irritant dermatitis
- Allergic dermatitis
- Photosensitivity
- Urticaria (hives)
- Skin cancer
- Eczema (Atopic dermatitis)
- Pigment disturbances
What is contact dermatitis? What are the 2 sub-groups?
Contact dermatitis: inflammation of the skin through contact with toxicants
Sub-groups:
1. Irritant dermatitis
(80% of dermatitis cases)
2. Allergic dermatitis
What is irritant dermatitis?
A general inflammatory response to a sensitized molecule or chemical. There is no single mechanism of action because many cytokines are involved. Intensity is related to dose, therefore more exposure = more intense reaction. There is a lot of variability between individuals.
What are the 2 sub-groups of irritant dermatitis? Explain them.
- Chronic cumulative irritation (most of the time):
• repeated exposures (causing redness, dryness, etc.)
• mild irritants such as soaps, detergents,
solvents - Acute irritation (less individual variability):
• also called 2nd-degree chemical burn
• substantially disrupts the cornified layer
• strong acids, alkalies, oxidizing & reducing
agents
Give an example of a substance that causes acute irritant dermatitis.
Wet cement:
• Very alkaline (i.e. basic): pH 12-14
• Sand and small particles = skin irritation
• Can’t feel burn from basic substances right away so a lot of damage can be done before you notice!
Note: It’s also extra bad because it is sandy/grainy so it causes damage to your skin barrier so the burns can get even deeper past the epidermis.
