Toxic Responses of the Skin Flashcards
Skin as a barrier
- protects the body against external insults, thus maintaining _____________.
- participates in ________, __________, __________, __________,
__________, and _________regulation. - may react to noxious physical agents with various defensive mechanisms preventing its widespread ___________and/or ___________injuries
homeostasis
thermal; electrolyte; hormonal; metabolic; antimicrobial; immune
cutaneous; internal
This layer of the skin is also known as the stratum basale. This is where cell division happens
Stratum germinativum
This layer of the skin has desmosomes. This layer gives strength, and flexibility of the skin
Stratum spinosum
This layer of the skin has dead keratinocytes and provides protection
Stratum corneum
This layer of the skin, though only present in the palms and face, is between the stratum corneum and stratum granulosum
Stratum lucidum
stratified squamous epithelium consisting primarily of keratinocytes
interfollicular epidermis
Melanocytes are stimulated by ___________________ in the epidermis to produce melanin granules which are extruded and taken up by the surrounding keratinocytes and become pigmented.
ultraviolet light
dendritic, antigen presenting cells involved in the immune response of skin to foreign xenobiotics.
langerhans cells
T/F: The langerhans cells contributes in the regulation of the immune system. However, its presence is limited to some parts of the body
False. Because it is found all over the body
the stratum corneum is formed during program of _____________________, and is the primary barrier to ______________________
terminal differentiation; percutaneous absorption
The stratum corneum…
once compromised, it can permit great ____________ (increase/decrease) of the uptake of poorly permeable substances.
increase
The stratum corneum…
having _________ properties, it prevents water loss from underlying tissues by __________.
hydrophobic; evaporation
The stratum corneum is ordinarily hydrated (typically ____% water) or the moisture residing in corneocyte protein.
20
The degree of uptake through the skin depends on the details of _________ conditions
exposure
T/F: the degree of uptake is proportional to solute concentration, time, and the amount of skin surface exposed.
True
What are the two intrinsic factors that contribute to the absorption rate of a given compound?
Hydrophobicity and Rate of diffusion through the barrier
Identify if the intrinsic factor is hydrophobicity or rate of diffusion
affects ability to partition into epidermal lipid.
Hydrophobicity
Identify if the intrinsic factor is hydrophobicity or rate of diffusion
hydrophobic agents of low MW permeate the skin better than those of high MW or those that are hydrophilic
Rate of diffusion
Identify if the intrinsic factor is hydrophobicity or rate of diffusion
For small molecules, hydrophobicity is a dominant factor in penetration
Rate of dissusion
Identify if the intrinsic factor is hydrophobicity or rate of diffusion
partitioning agent into the skin is greatly affected by its solubility in or adhesion to the medium in which it is applied.
Hydrophobicity
Identify if the intrinsic factor is hydrophobicity or rate of diffusion
inverse function of molecular weight (MW) or molecular volume.
Rate of diffusion
Identify if the intrinsic factor is hydrophobicity or rate of diffusion
a measure is the commonly used octanol/water partitioning ratio (Kow).
Hydrophobicity
Identify if the intrinsic factor is hydrophobicity or rate of diffusion
once in the stratum corneum, may diffuse only very slowly into less hydrophobic.
Hydrophobicity
T/F: In percutaneous absorption, diffusion through the epidermis is considerably faster at some anatomical sites than others.
True
T/F: foot sole > palm > forehead > abdomen > scrotum.
False.
foot sole > palm > scrotum > forehead > abdomen.
Absorption through the _________________ is usually neglected because the combined appendageal surface area is a relatively small fraction of the total available area for uptake.
epidermal appendages
Transdermal Drug Delivery
T/F: Its advantages is providing a steady infusion of drug over extended periods, however there is a risk of large variations in plasma concentrations
False. …. avoiding large variations in plasma concentrations
Transdermal Drug Delivery
T/F: It prevents exposure to the acidic pH of the stomach, thus preventing biodegradation
True
Transdermal Drug Delivery
T/F: It avoids biotransformation in the gastrointestinal tract from first pass removal by the liver.
True
Measurements of penetration
For risk assessment and pharmaceutical design, the most useful subject for experimentation is ___________.
human skin
Measurements of penetration
For in vitro work, _______________________ can be employed in special diffusion chambers.
excised split thickness skin
Measurements of penetration
A simpler setup commonly uses cadaver skin with the ________________ removed.
lower dermis
Measurements of penetration
To simplify determination of penetration kinetics, _________ may be employed and the _________ blood flow monitored to measure penetration.
skin flaps; capillary
Biotransformation
The ability of the skin to ____________ chemicals that diffuse through it contributes to its barrier function.
metabolize
Biotransformation
What are the major sites of biotransformation in the skin?
epidermis and pilosebaceous units
Biotransformation
What are the enzymes that are expressed in the skin that participate in biotransformation?
cytochrome P450, epoxide hydrolase, UDP glucuronosyltransferase, quinone reductase, and glutathione transferases
Biotransformation
What are the other metabolic enzyme activities detected in human epidermal cells?
sulfatases, β glucuronidase, N-acetyltransferases, esterases, and reductases.
Biotransformation
The ______________ region of the stratum corneum has catabolic activities (e.g., proteases, lipases, glycosidases, and phosphatase)
intercellular
T/F: Contact dermatitis falls into two major categories, irritant and allergic, which cannot co-exist
False. irritant and
allergic may co-exist:
The irritant and allergic categories of contact dermatitis both involve inflammatory responses. What are its clinical characteristics in areas of direct contact with the chemical?
erythema (redness), induration (thickening and firmness), scaling (flaking), and vesiculation (blistering)
T/F: Irritant dermatitis arises from the direct action of agents on the skin on a high concentration and on brief exposure.
False. Long exposure
Certain chemicals at sufficient concentration produce an acute irritation or ________________ chemical burn.
second-degree
T/F: Strong acids and alkalis can produce cytotoxicity directly, but oxidizing or reducing agents produce it indirectly.
False. Strong acids, alkalis, and powerful oxidizing or reducing agents can produce cytotoxicity directly.
Contact with a variety of plants can also have irritant effects, resulting in the production of proinflammatory cytokines from keratinocytes. What are these proinflammatory cytokines?
IL1α, IL1β, and TNFα
In irritant dermatitis, response to exposure varies depending on the ______________ of the anatomic site.
sensitivity
T/F: The eyelids are quite sensitive, and the forearm is more sensitive than the back
False. the back is more sensitive than the forearm
T/F: Individuals also vary greatly in sensitivity to irritant dermatitis, where atopic individuals are the most sensitive to irritants
True
T/F: In chemical burns (corrosion), extremely corrosive and reactive chemicals may produce immediate liquefactive necrosis that results in substantial tissue damage, with
ulceration and sloughing
False. Coagulative necrosis
Chemical burns (corrosion) are sometimes referred to as a ________________ chemical burn
third-degree
In chemical burns, a necrotic tissue can act as a _________________ resulting in either continued cutaneous damage or percutaneous absorption and systemic injury after exposure.
chemical reservoir
T/F: Allergic contact dermatitis is an immediate hypersensitive reaction because it is T-cell mediated
False. It is a delayed hypersensitive reaction
During sensitization in allergic contact dermatitis, the chemical hapten must penetrate the skin and become attached to _____________
carrier proteins
In allergic contact dermatitis, complete antigens are processed by _______________ and presented to ____________________ in regional lymph nodes.
Langerhans cells; type 1 T-helper cells
T/F: In allergic contact dermatitis, subsequent exposure to the same antigen results in a minimized immune response due to desensitization after adaptation to the allergens
False. Amplified immune response characterized by dermal infiltration and spongiosis.
Identify the type of contact allergen:
Bacitracin
antibiotics
Identify the type of contact allergen:
chlorhexidine
antiseptics
Identify the type of contact allergen:
formaldehyde
personal care products
Identify the type of contact allergen:
neomycin
antibiotics
Identify the type of contact allergen:
chloroxylenol
antiseptics
Identify the type of contact allergen:
formaldehyde releasers
personal care products
Identify the type of contact allergen:
polymyxin
antibiotics
Identify the type of contact allergen:
dichlorophene
antiseptics
Identify the type of contact allergen:
methylchloroisothiazolone/ methylisothiazolinone (MCI/ MI)
personal care products
Identify the type of contact allergen:
aminoglycosides
antibiotics
Identify the type of contact allergen:
glutaraldehyde
antiseptics
Identify the type of contact allergen:
ethylenediamine
personal care products
Identify the type of contact allergen:
sulfonamides
antibiotics
Identify the type of contact allergen:
thimerosal (merthiolate)
antiseptics
Identify the type of contact allergen:
lanolin
personal care products
Identify the type of contact allergen:
benzocaine
antibiotics
Identify the type of contact allergen:
mercurials
antiseptics
Identify the type of contact allergen:
p-Phenylenediamine
personal care products
Identify the type of contact allergen:
corticosteroids
antibiotics
Identify the type of contact allergen:
triphenylmethane dyes
antiseptics
Identify the type of contact allergen:
propylene glycol
personal care products
Identify the type of contact allergen:
fragrances
personal care products
T/F: Erythema is an adverse response to electromagnetic radiation, an evident feature of UV radiation exposure observed in photosensitivity
True
This is the smallest dose of UV light needed to induce an erythematous response, varies greatly from person to person.
minimal erythema dose (MED)
What are the environmental conditions that affect UV induced injury:
duration of exposure, season, altitude, body site, skin pigmentation, and previous exposure.
Adverse responses to electromagnetic radiation
Chronic exposure to radiation induces a variety of characteristic skin changes like
1. ______________ changes such as freckling and hypomelanotic
areas,
2. wrinkling, _______________ (fine superficial blood vessels),
3. _________________ (precancerous lesions),
4. and ____________ skin lesions such as basal and squamous cell
carcinomas and malignant _____________.
Pigmentary
telangiectasias
actinic keratoses
malignant; melanoma
T/F: Phototoxic reactions may be produced either by systemic or topical exposures.
True
In acute reactions (phototoxicity), the skin may appear ______, and _________ within minutes to hours after UV light exposure
red; blister
Chronic phototoxic responses may result in ______________ and ____________ of the affected areas.
hyperpigmentation; thickening
T/F: UVB (290 to 320 nm) is the most commonly responsible; UVA (320 to 400 nm) may occasionally be involved in phototoxicity
False. UVA (320 to 400 nm) is the most commonly responsible; UVB(290 to 320 nm) may occasionally be involved.
T/F: photoallergy is a type IV delayed hypersensitivity reaction, leading typically to eczema.
True
T/F: photoallergy does not require prior sensitization to the chemical
False. It requires prior sensitization
T/F: Photocontact dermatitis and systemic photoallergy are results of induction and subsequent elicitation of reactions from topical exposure, however, they do not have the same mechanism as that for allergic contact dermatitis
False. They have the same mechanism as that of allergic contact dermatitis, though UV light is necessary to convert a potential photosensitizing chemical into a hapten that elicits an allergic response.
This may develop for those allergens to which IgE antibodies have been elicited by previous or ongoing exposure, through an immediate type I hypersensitivity reaction.
Urticaria
In urticaria, ________ are raised wheals that usually itch or sting and may appear reddish.
Hives
Major causes of acute urticaria
food allergies and pharmaceuticals
What are the pigmentary disturbances
hyperpigmentation, exogenous hyperpigmentation, hypopigmentation, leukoderma (vitiligo) and depigmentation
this pigmentary disturbance results from increased melanin production or deposition of endogenous or exogenous pigment in the upper dermis.
hyperpigmentation
this pigmentary disturbance can arise from deposition of metals and drugs in dermal tissue.
exogenous hyperpigmentation
this pigmentary disturbance is a loss of pigmentation from melanin loss, melanocyte damage, or vascular abnormalities.
hypopigmentation
these pigmentary disturbances denote complete loss of melanin from the skin imparting porcelain-white appearance.
Leukoderma (vitiligo) and depigmentation
T/F: Comedogenic chemicals induce comedone lesions, which may be open or closed (blackhead or whitehead, respectively, in the vernacular).
True
T/F: papules, pustules, cysts, and scars may complicate the process of healing
True
This condition happens when hair follicles and associated sebaceous glands become clogged with compacted keratinocytes that are bathed in sebum.
acne
T/F: the most evident pigmentary change due to melanin is observed in closed comedones
False. Open comedones
This acne is characterized red, cystic, painful, and inflamed
hormonal acne
this acne is characterized by tiny white bumps, not painful and red
product acne
this type of acne is characterized by tiny black spots on the skin
blackheads
this type of acne is characterized by small bumps sticking out from your skin
yuck. char lang shempre whiteheads ang sagot
this type of acne is characterized by a pimple with a white colored head that contain pus
pustules
this type of acne is characterized by large, inflamed bumps that feel firm to the touch
nodules
this type of acne is large, painful, pus-filled bumps. These are softer than nodules
cysts
T/F: Inflammatory acnes include blackheads and whiteheads.
False. Non-inflammatory acnes don’t cause swelling and includes blackheads and whiteheads. Inflammatory acnes are pimples that are red and swollen
It is caused by exposure to polyhalogenated aromatic hydrocarbons, and one of the most disfiguring forms of acne in humans
chloracne
in chloracne, ___________ and strawcolored _________ are typically present behind the ears, around the eyes, and on the shoulders, back, and genitalia.
comedones; cysts
what are the other characteristics present in chloracne, in addition to acne?
hypertrichosis (increased hair in atypical locations), hyperpigmentation, brown discoloration of the nail, conjunctivitis, and eye discharge
Granulomatous disease occurs infrequently toward a variety of agents introduced into the skin through _____________ or after ______________ or abrasion.
injection; laceration
T/F: In granulomatous disease, persistent lesions with abundant inflammatory cells can be produced, resembling chronic infectious condition and present diagnostic challenges.
True
Many substances can produce granulomatous reactions, including
_______, talc, paraffin or mineral oil, ____________, and ___________.
silica; beryllium; gadolinium
Metallic _________ and ___________ compounds, formerly used in deodorants, and _____________ (containing cobalt, chromium, mercury, lead, iron, cadmium, and manganese compounds) can also induce granulomatous reactions that, in rare cases, can be induced by intense ______ treatment.
mercury; zirconium; tattoo dyes; light
T/F: Toxic epidermal necrolysis (TEN) is a rare life-threatening skin disease.
True
T/F: Stevens-Johnson syndrome (SJS) is a condition much worse than toxic epidermal necrolysis (TEN)
False. SJS severity is below 10% while TEN is above 30%. The overlap of SJS and TEN is between 10-30%
T/F: Toxic epidermal necrolysis involves detachment of ≥10% of the epidermal surface from the dermis, commonly accompanied by severe erosions of the mucous membranes.
False. ≥30%
______________________ involvement in toxic epidermal necrolysis can result in gastrointestinal hemorrhage, respiratory failure, ocular abnormalities, and genitourinary complications.
Mucous membrane
Nearly 200 drugs have been reported to cause toxic epidermal necrolysis with major contributors being ____________, nonsteroidal anti-inflammatories, antibacterial sulfonamides, ___________, and ______________
anticonvulsants; allopurinol; nevirapine
Mechanisms leading to this idiosyncratic drug reaction (toxic epidermal necrolysis) are under scrutiny and current hypotheses identify ______________ and ________ background as contributing factors.
HLA genotype; ethnic
T/F: Radiation from non-ionizing wavelengths to ultraviolet wavelengths has been shown to cause skin cancer.
False. Ionizing wavelengths
Shortly after the discovery of radioactive elements at the turn of the twentieth century, it was observed that ________ could cause severe burns, squamous cell carcinoma, and basal cell carcinomas.
X-rays
T/F: Most skin cancers in the United States now are X-ray-induced.
False. UV-induced
What are the most common UV-induced skin cancers?
NMSC and cutaneous malignant melanoma
T/F: UV light also has immunosuppressive effects that may help skin tumors survive.
True
T/F: Skin cancer incidence is highest in the tropics and in pale complexioned whites.
True
T/F: Even when it does not cause cancer in normal individuals, sun exposure leads to premature aging of the skin.
True
T/F: Sunblock lotions is encouraged while sunbathing is discouraged
True
Substances rich in ____________________________ (coal tar, creosote, pitch, and soot) are skin carcinogens in humans and animals.
polycyclic aromatic hydrocarbons
What causes the production of electrophilic epoxides, which forms DNA adducts, from polycyclic aromatic hydrocarbons?
oxidative biotransformation
It is produced by rearrangement of the epoxides, and it can be oxidized further to quinones which yields active oxygen species.
Phenols
T/F: Active oxygen species are not toxic electrophiles
False
T/F: Occupations at risk of skin cancer from exposure to these compounds (e.g., roofing) often involve considerable sun exposure
True
The observed incidence of squamous cell carcinomas in ________________ is taken as evidence of a general carcinogenic risk for humans.
mouse skin
T/F: Squamous cell carcinoma pathogenesis in mouse skin has general applicability to human squamous cell carcinomas.
True
An advantage of the mouse skin carcinogenesis model is the ability to ___________ the neoplastic process into stages of initiation, promotion, and progression depending on experimental design.
separate
T/F: Irritants are more difficult to resolve as compared to allergies that manifests immediately.
False. Allergies are more difficult to resolve because its manifestations do not show immediately, and gradually worsens (crescendo). While irritants have immediate manifestations
