17: Cutaneous Photobiology Flashcards
1
Q
What is the role of chromophores in the skin regarding photobiologic responses?
A
Chromophores in the skin absorb radiation, which is necessary for a photobiologic response to occur.
2
Q
How does UV radiation contribute to skin cancer formation?
A
UV radiation causes DNA damage, leading to sunburn, tanning, and mutations that can result in skin cancer.
3
Q
What are the differences between UVB and UVA radiation in terms of skin penetration?
A
UVB primarily penetrates the epidermis, while UVA penetrates deeper into the dermis.
4
Q
What are the photobiological consequences of visible light and infrared radiation exposure?
A
The consequences include erythema, tanning, and degradation of cellular matrix proteins.
5
Q
What is the significance of the 1st law of photochemistry in relation to skin and light exposure?
A
The 1st law of photochemistry states that light must first be absorbed by a chemical substance, such as a chromophore in the skin, for a photochemical reaction to occur.
6
Q
What are the main sources of ultraviolet radiation?
A
The main sources of ultraviolet radiation include sunlight and artificial sources like fluorescent and halogen lamps.
7
Q
What is the impact of photoaging on the skin?
A
Photoaging leads to irreversible UV-induced accumulation of undegradable abnormal proteins, affecting all compartments of the skin.
8
Q
What types of radiation are classified as non-ionizing radiation?
A
Non-ionizing radiation includes ultraviolet radiation (UVR), visible light, and infrared radiation.
9
Q
What happens to a chromophore in the ground state when it absorbs the energy of a photon?
A
Electrons are raised to a higher orbit, resulting in an excited state.
10
Q
What are the two types of excited states of a chromophore?
A
- Singlet state: no change in spin.
- Triplet state: change in spin; longer-lived (seconds).
11
Q
What is a photoproduct?
A
A new, different molecule formed by a photochemical reaction upon photoexcitation.
12
Q
What is the role of Vitamin D in the body?
A
Regulates calcium and phosphorus metabolism, primarily by increasing the flow of calcium into the bloodstream.
13
Q
What are the consequences of Vitamin D deficiency?
A
Impaired bone mineralization leading to conditions such as rickets in children, osteomalacia in adults, and osteoporosis.
14
Q
What factors can lead to Vitamin D deficiency?
A
- Inadequate intake
- Inadequate sunlight exposure
- Disorders that limit absorption
- Conditions that limit conversion of Vitamin D into active metabolites (e.g., liver or kidney diseases).
15
Q
Who is most vulnerable to low Vitamin D levels?
A
- Elders
- Individuals living at high altitudes with long winters
- Obese individuals
- Individuals with dark skin pigmentation living at high altitudes.
16
Q
What are the symptoms of Vitamin D toxicity?
A
Symptoms include muscle weakness, apathy, headache, confusion, anorexia, irritability, nausea, vomiting, and bone pain.
17
Q
What is the safe upper limit for adult intake of Vitamin D?
A
10,000 IU.
18
Q
What is the significance of Stokes law in fluorescence and how does it relate to the excitation of protoporphyrin IX?
A
Stokes Law states that the wavelengths of fluorescence are always longer (less energetic) than the exciting wavelength.
19
Q
How does Vitamin D deficiency affect bone health and what are the conditions associated with it?
A
Vitamin D deficiency leads to impaired bone mineralization, resulting in rickets, osteomalacia, and osteoporosis.
20
Q
What are the symptoms and complications associated with Vitamin D toxicity?
A
Vitamin D toxicity can manifest as hypercalciuria or hypercalcemia leading to muscle weakness, apathy, headache, confusion, anorexia, irritability, nausea, vomiting, and bone pain.
21
Q
What are the two major sources of vitamin D and how is it absorbed?
A
- Exogenous sources (diet): absorbed in the small intestine.
- Endogenous synthesis: Vitamin D is synthesized in the skin upon exposure to UVB radiation.
22
Q
What is the role of UV radiation in the immune system?
A
- Proinflammatory properties: induces sunburn and triggers inflammatory photodermatoses.
- Antiinflammatory properties: reactivation of labial herpes simplex with UV exposure.
23
Q
What are the beneficial effects of UV-induced immunosuppression?
A
- Prevention of autoimmune reactions against self-antigens.
24
Q
What are the potential downsides of photo-immunosuppression due to UV exposure?
A
- Prevents recognition of UV-induced tumor antigens, which can promote photocarcinogenesis.
25
What are the effects of UV radiation on DNA and RNA?
1. **DNA**: Formation of DNA damage.
2. **RNA**: Formation of RNA damage.
26
A patient with systemic lupus erythematosus experiences a flare after UV exposure. What immunological mechanism is involved?
UV exposure triggers migration of Langerhans cells to lymph nodes and release of anti-inflammatory mediators like IL-10.
27
A patient with vitamin D deficiency is advised to increase sun exposure. What is the optimal wavelength for cutaneous vitamin D synthesis?
The optimal wavelength for vitamin D synthesis is in the UVB range, peaking at 297 nm.
28
A patient with dark skin pigmentation requires more sunlight for vitamin D synthesis. Why is this the case?
Higher melanin content in dark skin absorbs more UV radiation, reducing the amount available for vitamin D synthesis.
29
A patient with polymorphous light eruption has reduced UV-induced immunosuppression. How does this condition protect against photocarcinogenesis?
Reduced UV-induced immunosuppression enhances the immune system's ability to recognize and eliminate UV-induced tumor antigens.
30
A patient with systemic lupus erythematosus is advised to avoid UV exposure. What chromophore is involved in UV-induced immunosuppression?
The chromophore involved is urocanic acid, which undergoes UV-induced isomerization.
31
A patient with systemic lupus erythematosus experiences a flare after UV exposure. What is the role of IL-10 in this process?
IL-10 is an anti-inflammatory mediator released during UV-induced immunosuppression.
32
A patient with sunburn exhibits erythema and pain. What inflammatory mediators are involved in this response?
Inflammatory mediators involved include serotonin, prostaglandins, IL-1, IL-6, IL-8, and TNF-alpha.
33
A patient with systemic lupus erythematosus is advised to avoid UV exposure. What is the role of Langerhans cells in UV-induced immunosuppression?
Langerhans cells migrate from the epidermis to lymph nodes during UV-induced immunosuppression.
34
What are the protective mechanisms of the skin in response to UV-induced inflammation?
The skin's protective mechanisms include increased pigmentation, skin thickening, and molecular adaptations.
35
What are the skin phototypes and their significance in UVR exposure?
Skin phototypes range from Type I (always burns, never tans) to Type VI (darkly pigmented) and help assess the risk of skin damage and cancer from UV exposure.
36
What is the role of melanin in UVR-induced tanning?
Melanin has UV-absorbing properties that shield the nuclei against DNA-damaging effects of subsequent UV exposures.
37
What are the stages of heme biosynthesis in relation to photodermatoses?
The stages of heme biosynthesis related to photodermatoses include early stage involving nonaromatic intermediates.
38
What is the role of melanin in UVR-induced tanning?
Melanin plays a crucial role in UVR-induced tanning as it has UV-absorbing properties that shield the nuclei against the DNA-damaging effects of subsequent UV exposures. This helps in reducing the risk of skin damage and mutations.
39
What are the stages of heme biosynthesis in relation to photodermatoses?
The stages of heme biosynthesis related to photodermatoses include:
1. **Early stage** - involves nonaromatic intermediates that do not act as chromophores.
2. **Late stage** - involves aromatic intermediates that act as chromophores, leading to phototoxic reactions upon exposure to UVR or visible light.
40
What is the likely diagnosis for a patient with erythema and blistering 12 hours after sun exposure?
The likely diagnosis is sunburn (solar erythema).
## Footnote
The chromophore responsible is DNA.
41
What is the underlying mechanism for xeroderma pigmentosum and its effect on minimal erythema dose?
Xeroderma pigmentosum is caused by defective DNA repair mechanisms, leading to decreased UVB minimal erythema dose and acute photosensitivity.
42
What histological changes are expected in a patient who develops hyperpigmentation three days after UVB exposure?
Histological changes include an increase in basal and suprabasal melanin in the epidermis. Melanin absorbs UV radiation, shielding nuclei from DNA damage.
43
What ingredient in a new perfume is likely responsible for phototoxic dermatitis?
The likely ingredient is bergamot oil (5-methoxypsoralen), which absorbs within the UVA range.
44
What is the chromophore involved in erythropoietic protoporphyria and what damage does it cause?
The chromophore is protoporphyrin, which is lipophilic and causes capillary damage with dermal necrosis and pain.
45
What histological changes are expected in the epidermis of a patient with sunburn?
Histological changes include epidermal edema, spongiosis, apoptotic keratinocytes (sunburn cells), and vasodilation.
46
What are the histological features of sunburn and how do they relate to the skin's response to UV exposure?
Histological features of sunburn include:
- **Epidermal edema** with spongiosis
- **Few apoptotic keratinocytes** (sunburn cells)
- **Depletion of Langerhans cells**
- **Vasodilation**
- **Mixed inflammatory infiltrate** with lymphocytes and neutrophils
These features indicate the skin's inflammatory response to UV exposure, leading to increased blood flow and immune cell activity to repair damage and protect against further injury.
47
How does the skin's response to UV-induced inflammation contribute to protective mechanisms against DNA damage?
The skin's response to UV-induced inflammation includes:
1. **Epidermal keratinocytes hyperproliferate**, leading to thickening of the epidermis and stratum corneum.
2. This thickening **decreases penetration of UVR** to the basal layer, thereby reducing DNA damage and mutation in stem cells.
3. **Increased pigmentation** serves as a natural barrier against UV radiation.
4. **Molecular adaptations** occur to enhance the skin's resilience to UV damage.
48
What role does melanin play in UVR-induced tanning and how does it protect against DNA damage?
Melanin plays a crucial role in UVR-induced tanning by:
- **Absorbing UV radiation**, which shields the nuclei of skin cells against the DNA-damaging effects of subsequent UV exposures.
- **Increasing pigmentation** in response to UV exposure, which serves as a protective mechanism against further damage.
49
What are the implications of skin phototypes in relation to an individual's risk for long-term effects of UVR exposure?
Skin phototypes are indicators of an individual's risk for long-term effects of UVR exposure, including:
| Skin Phototype | Burning and Tanning Reactions | Color of Unexposed Skin |
|----------------|------------------------------|-------------------------|
| I | Always burns, never tans | Pale white |
| II | Always burns, tans easily | White |
| III | Sometimes burns, can tan | White |
| IV | Usually does not burn, tans easily | White to light brown |
| V | Rarely burns, tans easily | Brown; moderately pigmented |
| VI | Burns only with very high UVR doses, tans | Dark brown to black; darkly pigmented |
Individuals with lighter skin types (I and II) are at a higher risk for photocarcinogenesis compared to those with darker skin types (V and VI).
50
What are the common conditions associated with polymorphous light eruption and solar urticaria?
Polymorphous light eruption and solar urticaria are heterogeneous conditions that involve various chromophores, ranging from UVB, UVA, visible light, to infrared radiation.
51
What is the primary chromophore involved in the treatment of psoriasis through phototherapy?
The primary chromophore involved in the treatment of psoriasis through phototherapy is DNA.
52
What is the penetration depth of UVB radiation in the skin, and what are its therapeutic effects?
UVB radiation penetrates the epidermis and upper layers of the dermis, with therapeutic effects against conditions like psoriasis.
53
What is the significance of narrowband UVB phototherapy in treating skin conditions?
Narrowband UVB phototherapy, specifically at wavelengths of 311 to 312 nm, is significant for its therapeutic effects against psoriasis and other skin conditions such as atopic dermatitis and vitiligo.
54
What types of DNA damage are induced by UV radiation, and what are the common products formed?
UV radiation induces types of DNA damage such as cyclobutane pyrimidine dimers (CPD) and 6,4-pyrimidine-pyrimidone photoproducts, which can lead to single and tandem base substitution mutations.
55
How does chronic exposure to UV light affect the risk of skin malignancies?
Chronic exposure to UV light increases the risk for cutaneous malignancies such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma, and Merkel cell carcinoma.
56
What is the role of the nucleotide excision repair system in response to UV-induced DNA damage?
The nucleotide excision repair system functions to remove UV-induced DNA damage, such as cyclobutane pyrimidine dimers, restoring the normal DNA sequence if the damage is repaired.
57
What are UV-signature mutations and how do they relate to skin cancer development?
UV-signature mutations are inactivating mutations in crucial genes caused by UV exposure, which can lead to malignant transformation and clonal expansion of individual cells, resulting in skin cancers.
58
What is the therapeutic wavelength range for a patient with psoriasis undergoing narrowband UVB phototherapy?
The therapeutic wavelength range is 311-312 nm. It induces cytotoxic and proapoptotic effects on hyperproliferating activated T cells.
59
What diagnostic tools can identify triggering wavelengths for a patient with chronic actinic dermatitis?
Diagnostic tools include determination of minimal erythema dose (UVA-MED, UVB-MED) and photopatch testing.
60
What are the typical UV-signature mutations in a patient with melanoma?
Typical mutations are C → T and CC → TT at dipyrimidine sites, formed by cyclobutane pyrimidine dimers and 6,4-pyrimidine-pyrimidone photoproducts.
61
What is the role of psoralen in PUVA therapy for psoriasis?
Psoralen intercalates with DNA and enhances UVA's DNA-damaging effects, bringing them into the therapeutic range.
62
What UV-induced DNA damage leads to mutations in tumor suppressor genes in melanoma?
UV-induced DNA damage, such as cyclobutane pyrimidine dimers and 6,4-pyrimidine-pyrimidone photoproducts, leads to mutations in tumor suppressor genes.
63
How does UV-induced DNA damage lead to mutations in p53?
UV-induced DNA damage, such as cyclobutane pyrimidine dimers, leads to mispairing during replication, resulting in mutations in p53.
64
What are the typical UV-signature mutations in a patient with squamous cell carcinoma?
Typical UV-signature mutations are C → T and CC → TT at dipyrimidine sites.
65
What wavelengths are most likely to trigger polymorphous light eruption?
Wavelengths most likely to trigger polymorphous light eruption include UVB, UVA, and visible light.
66
What are the implications of chronic UV light exposure on skin health?
Chronic exposure to UV light increases the risk for various cutaneous malignancies, including:
- Basal Cell Carcinoma (BCC)
- Squamous Cell Carcinoma (SCC)
- Malignant Melanoma
- Merkel Cell Carcinoma
67
How does narrowband UVB phototherapy work in treating psoriasis?
Narrowband (nb) UVB phototherapy operates at wavelengths of 311 to 312 nm, which penetrate the epidermis and upper layers of the dermis. Its therapeutic effects against psoriasis include:
- Reducing hyperproliferation of activated T cells, which are sensitive to UVB's cytotoxic effects.
- Inducing apoptosis in affected skin cells, leading to improved skin condition.
68
What types of DNA damage are induced by UV radiation, and what are the potential consequences?
UV radiation induces specific types of DNA damage, primarily:
- Cyclobutane Pyrimidine Dimers (CPD)
- 6,4-Pyrimidine-Pyrimidone Photoproducts
These damages can lead to single and tandem base substitution mutations (C→T and CC→TT) at di-pyrimidine sites, termed UV-signature mutations.
69
What role does photodynamic therapy (PDT) play in treating skin neoplasms?
Photodynamic therapy (PDT) utilizes a photosensitizer, such as 5-amino-levulinic acid (5-ALA), which circumvents rate-limiting steps in heme biosynthesis, leading to increased protoporphyrin IX.
70
What are the mechanisms of UVR-induced mutation formation in DNA?
The mechanisms include:
1. **Classic Pathway**: Adjacent pyrimidines dimerize to form DNA photoproducts after direct excitation by photons.
2. **Melanin-Dependent Chemiexcitation Pathway**: Involves energy transfer from excited melanin fragments to DNA.
3. **Oxidative Pathway**: Involves a photosensitized reaction with singlet oxygen formed after excitation of a cellular chromophore.
71
What is the role of melanin in the chemiexcitation pathway?
In the chemiexcitation pathway, excited melanin fragments transfer energy to DNA, generating UV-signature mutations.
72
What is the role of UVA in the development of malignant melanoma?
UVA contributes to melanoma by generating reactive oxygen species and inducing DNA damage through the chemiexcitation pathway.
73
How do the classic pathway and the melanin-dependent chemiexcitation pathway differ in UVR-induced mutation formation?
The classic pathway involves adjacent pyrimidines reacting to form DNA photoproducts, while the melanin-dependent chemiexcitation pathway involves energy transfer from excited melanin fragments to DNA.
74
How does the oxidative pathway contribute to UVR-induced mutations?
The oxidative pathway involves a photosensitized reaction that generates singlet oxygen, leading to oxidative base modifications and common oxidative base lesions.
75
What is the role of CSA and CSB proteins in DNA repair?
CSA and CSB proteins are involved in the process of transcription-coupled DNA repair, which is initiated when damaged DNA in actively transcribed genes stalls the RNA polymerase.
76
How does global genome repair differ from transcription-coupled repair?
Global genome repair is initiated when damaged DNA in the remainder of the genome is bound by XPE and XPC gene products, while transcription-coupled repair is specifically for actively transcribed genes and involves CSA and CSB proteins.
77
What proteins are involved in unwinding the DNA during the repair process?
The unwinding of DNA during the repair process involves a complex of proteins including XPB and XPD gene.
78
What initiates DNA repair?
DNA repair is initiated when damaged DNA in actively transcribed genes stalls the RNA polymerase.
79
What proteins are involved in unwinding the DNA during the repair process?
The unwinding of DNA during the repair process involves a complex of proteins including XPB and XPD gene products, which are also part of the basal transcription factor IIH (TFIIH).
80
What is the function of XPF and XPG nucleases in DNA repair?
XPF and XPG nucleases make single-strand cuts on either side of the DNA damage, releasing a 24- to 34-residue segment of DNA to facilitate repair.
81
Which proteins fill the gap left after DNA damage is repaired?
The gap left after DNA damage is repaired is filled by DNA polymerase, along with the proteins proliferating cell nuclear antigen (PCNA) and replication protein A (RPA).
82
What DNA repair mechanism counteracts UV-induced DNA damage?
The nucleotide excision repair (NER) system removes UV-induced DNA damage, such as cyclobutane pyrimidine dimers.
83
What proteins are involved in global genome repair?
Proteins involved in global genome repair include XPE, XPC, XPB, XPD, XPA, XPF, and XPG.
84
What is the role of nucleotide excision repair in preventing mutations?
Nucleotide excision repair removes UV-induced DNA damage, such as cyclobutane pyrimidine dimers, preventing mutations in tumor suppressor genes.
85
What is the role of CSA and CSB proteins in DNA repair?
CSA and CSB proteins are involved in stalling the RNA polymerase, which serves as a signal to initiate transcription-coupled DNA repair for damaged DNA in actively transcribed genes.
86
How do XPE and XPC gene products contribute to DNA repair?
XPE and XPC gene products bind to damaged DNA in the remainder of the genome, signaling the initiation of global genome repair to address UV-induced damage.
87
Describe the process of unwinding DNA during repair.
The unwinding of DNA during repair involves a complex of proteins, including XPB and XPD gene products, which are part of the TFIIH transcription factor complex. The XPA protein may stabilize the unwound DNA.
88
What is the function of XPF and XPG nucleases after UV damage?
XPF and XPG nucleases make single-strand cuts on either side of the damage, releasing a 24- to 34-residue segment of DNA, which is crucial for the subsequent repair steps.
89
What role does DNA polymerase play in DNA repair?
DNA polymerase fills the resulting gap after the removal of damaged DNA, in a process that involves proteins such as proliferating cell nuclear antigen (PCNA) and replication protein A (RPA).
90
What are the main signaling cascades in response to UVR-induced DNA damage?
The main signaling cascades include ATM (Ataxia Telangiectasia Mutated), ATR (Ataxia Telangiectasia and Rad3-related), p53, Chk1/Chk2, and p21.
91
How does p53 contribute to cell cycle regulation?
p53 contributes to cell cycle regulation by activating the G1/S checkpoint, inducing transcription of p21, mediating G2/M arrest, and inducing global genome nucleotide excision repair (GG-NER).
92
What is the role of the Fanconi anemia (FA)/BRCA pathway in DNA repair?
The Fanconi anemia (FA)/BRCA pathway mediates recombination repair of DNA damage, is dependent on ATR activation, and is involved in the repair of interstrand cross-links.
93
What are the effects of UV radiation on skin aging?
The effects of UV radiation include photoaging, actinic elastosis, and increased risk of skin cancer.
94
Which wavelengths of UV radiation are associated with skin cancer risk?
UVB contributes more to photocarcinogenesis, while UVA increases melanoma risk, especially with tanning parlor exposure.
95
What are the histological features of actinic elastosis?
Actinic elastosis is characterized by accumulation of fibrillary basophilic material in the dermis, yellowish thickening of the skin, and loss of elasticity.
96
What molecular changes contribute to deep wrinkles in photoaging?
Photoaging involves upregulation of elastin synthesis and accumulation of abnormal proteins like progerin.
97
What signaling pathways are activated in response to sunburn?
Signaling pathways activated include ATM/ATR, p53, and Chk1/Chk2, leading to cell cycle arrest and DNA repair.
98
What is the role of cathepsin K in actinic elastosis?
Cathepsin K is upregulated by UVA and promotes intracellular clearing, contributing to actinic elastosis.
99
What are the roles of ATM and ATR in response to UVR-induced DNA damage?
ATM and ATR are activated in response to both ionizing radiation and ultraviolet radiation, leading to various cellular responses including DNA repair.
100
What is the significance of translesional DNA synthesis?
Translesional DNA synthesis allows cells to bypass DNA lesions due to UVR-induced damage, enabling the continuation of DNA replication despite damage.
101
What are the differences in mechanisms by which UVA and UVB contribute to skin cancer risk?
UVB is more strongly associated with photocarcinogenesis, while UVA exposure increases melanoma risk through different mechanisms.
102
What are the characteristics of actinic elastosis?
Actinic elastosis is characterized by yellowish thickening of the skin, loss of elasticity, and deep wrinkles, differing from intrinsic skin aging.
103
What is Progerin and how is it related to aging?
Progerin is an abnormal splice variant of Lamin A, accumulates in aging cells, and is induced by UVA via oxidative stress.
104
What are the cutaneous responses to visible light?
Visible light can induce erythema, pigmentation, and photofermatoses. Key chromophores involved include porphyrins, melanin, and hemoglobin.
105
What are the effects of infrared radiation on the skin?
Infrared radiation is implicated in photoaging and erythema ab igne, affecting gene expression in dermal fibroblasts.
106
How does UVA exposure contribute to progerin levels?
UVA exposure induces oxidative stress and abnormal splicing, leading to increased progerin levels.
107
What chromophores are targeted in intense pulsed light (IPL) treatment?
Chromophores targeted include porphyrins, melanin, beta-carotene, riboflavin, bilirubin, and hemoglobin.
108
What chromophores are responsible for chronic actinic dermatitis?
Chromophores responsible include porphyrins, melanin, beta-carotene, riboflavin, bilirubin, and hemoglobin.
109
How does infrared radiation contribute to collagen loss in photoaging?
Infrared radiation induces matrix metalloproteinase expression in dermal fibroblasts, leading to collagen fiber loss.
110
What is the role of oxidative stress in increased progerin levels?
Oxidative stress induced by UVA exposure leads to abnormal splicing and increased progerin levels.
111
What is the role of matrix metalloproteinases in photoaging?
Matrix metalloproteinases degrade collagen fibers, contributing to deep wrinkles in photoaging.
112
What is the role of progerin in the aging process?
Progerin accumulates in aging cells, leading to wrinkling and increased laxity of the skin, and has an anticancer effect.
113
How does visible light exposure contribute to skin conditions?
Visible light can induce erythema, pigmentation, and photofermatoses, with chromophores involved including porphyrins and melanin.
114
What are the effects of infrared radiation on skin aging?
Infrared radiation affects gene expression in dermal fibroblasts, leading to loss of collagen fibers and contributing to photoaging.
