SKIN 6131 Flashcards
protects the body against external insults in order to maintain
internal homeostasis
skin
Skin is _______ of our body mass
10%
Skin is the most accessible organ in the body (t or f)
T
It participates directly in ________, _________, ________, ________, and _________
thermal, electrolyte, hormonal,
metabolic, and immune regulation
- Thick stratum
corneum—good physical
barrier - Common site of contact with
chemicals - Occlusion with protective
clothing
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Palm/soles
- Moist, occluded areas
- Chemical trapping
- Enhanced percutaneous
absorption
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Intertriginous areas
example of Intertriginous areas
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
axillae, groin, neck, finger webs, umbilicus, genitalia
- Exposed frequently
- Surface lipid interacts with
hydrophobic substances - Chemicals frequently
transferred rom hands
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Face
- Poor barrier function—thin
epidermis - Sensitive to irritants
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Eyelids
- Chemical trapping
- Occlusion
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Postauricular region
- Chemical trapping
- Hair follicles susceptible to
metabolic damage
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Scalp
- Increased sensitivity to
irritants - Impaired barrier function
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Atopic dermatitis
- Impaired barrier function
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Psoriasis
- Predisposition to skin
disorders - Variation in sensitivity to
irritants - Susceptibility to contact
sensitization
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Genetic Factors
- Vasodilation—improved
percutaneous absorption - Increased
sweating—trapping
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Temperature
- Increased
sweating—trapping
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Humidity
- Variation in relative humidity
- Chapping and wind-related
skin changes
(FACTORS INFLUENCING CUTANEOUS RESPONSES)
Season
Two major components of the skin that are separated by a basement membrane
epidermis and underlying dermis
Thickness of dermis
approximately 90% of the skin (has largely a supportive function)
span the epidermis and are embedded in the dermis
epidermal appendages
examples of epidermal appendages
- Hair follicles
- Sebaceous glands
- Eccrine glands
Layer that separates the dermis from underlying tissues
adipocytes
Accumulation of fat has a cushioning action
adipocytes
Somehow regulates our body temperature
adipocytes
Supply the bulbs of the hair follicles and the secretory cells of the eccrine (sweat) glands.
Capillaries
The ducts from these glands carry a dilute salt solution (that is sweat) to the surface of the skin, where its evaporation provides cooling sensation.
capillaries
Stratified squamous epithelium consisting primarily of keratinocytes
Interfollicular epidermis
Interfollicular epidermis is a stratified squamous epithelium consisting primarily of __________
keratinocytes
stimulated by ultraviolet light in the epidermis to produce melanin granules which are extruded and taken up by the surrounding keratinocytes and become pigmented
melanocytes
Widely distributed in the dermis, with occasional concentrations beneath the basal lamina and in the
papillae of hair follicles
Melanocytes
Dendritic, antigen-presenting cells usually involved in the immune response of skin to foreign agents,
particularly to xenobiotics
Langerhans cells (LCs)
Keratinocytes of the ___________ make up the germinative compartment
basal layer
- Cells become flattened and increase in volume nearly 40-fold.
- Lipid granules fuse with the plasma membrane, replacing the aqueous environment in the intercellular space with their contents.
Granular Layer
- Plasma membranes of these cells become permeable and cell organelles are degraded, while a
protein envelope is synthesized immediately beneath the plasma membrane.
Granular layer
Begins as keratinocytes leaving the basal layer, producing the outermost layer of the skin, the stratum corneum.
Terminal Differentiation
- Mature cells
- No longer viable
- ~80% keratin in content
- They are gradually shed from the surface and replaced from beneath
Corneocytes
process typically takes 2 weeks or basal cells to reach the stratum corneum and another 2 weeks to
be shed from the surface
Terminal Differentiation
When a basal cell divides, one of the progeny detaches from the basal lamina and migrates outward. Usually moves towards the skin surface
Terminal differentiation
The primary barrier to percutaneous absorption
Stratum corneum
the stratum corneum is formed during the process of ___________
terminal differentiation
the stratum corneum has _________ properties which prevents water loss from underlying tissues by evaporation
Hydrophobic
The SC is ordinarily hydrated which contains around ____ water or the moisture residing in corneocyte protein
20%
The lipids, a major component being ________, have a high content of long-chain ceramides removal of which seriously compromises barrier function as measured by TEWL
sphingolipids
Two intrinsic factors which contributes to the absorption rate of a given compound
- Hydrophobicity
- Rate of Diffusion through this barrier
- Affects its ability to partition into
epidermal lipid, and its rate of diffusion through this barrier - Usually computed using the
octanol/water partitioning ratio
Hydrophobicity
↑ Kow = ____________
hydrophobic
Partitioning of an agent into the skin is greatly affected by its solubility in or adhesion to the medium in which it is applied (including soil) (t or f)
T
hydrophobic compounds, once in the SC, may diffuse rapidly into less hydrophobic regions below (t or f)
F; very slowly
Hydrophobic substances with low MW permeate the skin better than those with high MW or those that are hydrophilic. (t or f)
T
A list in order of decreasing permeability under steady-state
conditions gives the following hierarchy
foot sole > palm > scrotum > forehead > abdomen
Absorption through the epidermal appendages is generally
neglected because the combined appendageal surface area is
a small fraction of the total available area for the absorption (t or f)
T
Advantages of transdermal drug delivery
- Provides a steady infusion or extended periods (typically 1 to 7 days) thereby avoiding large variations in plasma concentration
- Preventing exposure to the acidic pH of the stomach
- Avoid biotransformation in the
gastrointestinal tract or from first-pass removal by the liver
For risk assessment and pharmaceutical design, the
most useful subject or experimentation is ___________
(Measurement of Penetration)
human skin
human skin is always used for clinical trials (t or f)
(Measurement of Penetration)
T
Human skin can also be used for pre-clinical trials (t or f)
(Measurement of Penetration)
F
For in vitro work, _______________ can be employed in special diffusion chambers, though care is needed to preserve the viability of the living layer of epidermis.
(Measurement of Penetration)
excised split-thickness skin
A simpler setup commonly employed uses ____________ skin with the lower dermis removed.
(Measurement of Penetration)
cadaver
No life. Lacks biotransformation
capability but retains the barrier function of the SC
(Measurement of Penetration)
Cadaver skin
To simplify determination of penetration kinetics, __________ may be employed and the _____________ monitored to measure penetration.
Pig skin may be used
(Measurement of Penetration)
skin flaps; capillary blood
flow
The major sites of biotransformation or metabolism of the skin
is the _________ and __________ of the skin.
epidermis; pilosebaceous units
Enzymes participating in the biotransformation that are expressed in the skin
- CYP450
- epoxied hydrolase
- UDP glucuronosyltransferase
- Quinone reductase
- Glutathione transferase
Other metabolic enzyme activities detected in human epidermal cells include:
- Sulfatases
- β-glucuronidase
- N-acetyltransferases
- Esterases
- Reductases
The intercellular region of the stratum corneum has catabolic
activities…..
- proteases
- lipases
- glycosidases
- phosphatase
- Common skin disorder
- Accounts or over 90% of reported causes (of all occupational skin
disease) - involve in inflammatory processes and can have indistinguishable clinical characteristics of erythema
(redness), induration (thickening and firmness), scaling (flaking), and vesiculation (blistering) on areas directly contacting the chemical agent.
Contact dermatitis
two types of contact dermatitis
- irritant
- allergic
both may co-exist
- Arises from the direct contact of agents on the skin at a higher concentration or longer exposure
- Certain chemicals at sufficient concentration produce an acute irritation, sometimes called a second-degree chemical burn.
Irritant dermatitis
- It can be produced by strong acids, alkalis, and powerful oxidizing or reducing agents can substantially disrupt the cornified layer, producing cytotoxicity directly
Irritant dermatitis
Contact with a variety of plants can also have irritant effects resulting in the production of proinflammatory cytokines like
IL1a, IL1B, and TNFa from keratinocytes
the back is more sensitive than the forearm (t or f)
T
____________ are the most sensitive to irritants and exhibit a propensity to produce specific IgE antibodies to allergens and typically suffer from hay fever
Atopic individuals