1
Q
Disorders of Pigmentation &
Melanocytes
A
Freckle and lentigo
2
Q
Freckle
A
enhanced melanin transfer to
keratinocytes, and/or abnormality in pigment production
3
Q
Lentigo
A
Benign localized hyperplasia of melanocytes
4
Q
Melanocytic Nevus also known as?
A
Pigmented Nevus/Mole
5
Q
Melanocytic Nevus cause
A
acquired activating mutations
in components of the RAS signaling
pathway leading to proliferation of melaocytes
6
Q
Congenital nevus
A
Present at birth;
large variants have increased melanoma risk
7
Q
Blue nevus
A
Black-blue nodule;
often confused with
melanoma clinically
8
Q
Spindle and
epithelioid cell
nevus (Spitz nevus)
A
Common in children; red-pink
nodule; often confused with
hemangioma clinically
9
Q
Halo nevus
A
Host immune response against nevus cells and surrounding normal melanocytes
“white pigment ring”
10
Q
Dysplastic nevus
A
non smooth boarders
Potential marker or
precursor of melanoma
11
Q
Dysplastic Nevi cause
A
mutations in
NRAS and BRAF genes as well as increased
CDK4 activity
12
Q
what does NRAS and BRAF do?
A
activate the RAS system –> proliferation
13
Q
what does CDK4 do?
A
pushes the cell through the cell cycle
14
Q
Melanoma overall pathology
A
Caused by acquired mutations from exposure to UV radiation that affect cell cycle control, pro-growth pathways, and telomerase
15
Q
Melanoma cellular level cause
A
Mutation of CDKN2A (cell cycyle inhibitor) gene causing decreased production of P15, P16, and ARF —> more cell proliferation
and
increases in RAS and PI3K/AKT signaling promote cell growth and survival
16
Q
what does P16 do normally?
A
P16 inhibits CDK4 and CDK6
allowing retinoblastoma (RB)
tumor suppressor to block cell proliferation
17
Q
what does ARF do normally?
A
ARF enhances activity of p53 by inhibiting MDM2 which would otherwise stimmulate p53 degradation
18
Q
what does RAS and PI3K/AKT signaling do normally?
A
increases mTOR ->cell cycle progression
19
Q
What aspect of melanoma activates telomerase
A
Mutations of TERT gene encodes the catalytic subunit of telomerase
This results in upregulation of telomerase
20
Q
Benign Epithelial Tumors
A
Seborrheic Keratosis, Acanthosis Nigricans
21
Q
Seborrheic Keratosis cause
A
Activating mutations in fibroblast growth receptor factor-3 (FGFR3) drive the growth of the tumor
22
Q
Acanthosis Nigricans cause
A
Increased GF receptor (FGFR3) signaling
FGFR3is a receptor tyrosine kinase involved in cell growth and differentiation
its activating mutations causes stimulation of keratinocytes → epidermal hyperplasia
23
Q
Acanthosis Nigricans cause: Diabetes
A
in type 2 diabetes: hyperinsulinemia increases Insuline growth factor receptor 1
24
Q
Acanthosis Nigricans cause: Paraneoplastic
A
increasedTGF-1
25
why is Acanthosis Nigricans important to diagnose
sign of underlying condistions such as diabetes type 2 and GI adenocarcinoma
26
Premalignant & Malignant
Epidermal Tumors
Actinic keratosis, Squamous Cell Carcinoma, and Basal Cell Carcinoma
27
Actinic keratosis
Hyperkeratosis in sun-damaged skin
28
Actinic keratosis cause
Superficial dermis contains thickened elastic fibers
* Likely a result of abnormal elastic fiber synthesis by sun- damaged fibroblasts
29
Squamous Cell Carcinoma cause
DNA damage from exposure to UV
light affecting the function of p53
30
Basal Cell Carcinoma cause
Aggressive cutaneous tumor caused by mutations that activate the Hedgehog signaling pathway
Associated with UV light exposure
31
Hedgehog signaling pathway
associated with basal cell carcinoma
32
Hedgehog signaling pathway: when SHH is binding....
SMO gets released from PTCH
normal development of tissue
33
Hedgehog signaling pathway: mutation with PTCH causes what?
unregulated cell division as SMO must remain active
34
Acute Inflammatory Dermatoses
Urticaria
35
what does uticaria mean
HIVES
(sorry i had to make this one bc i seriously cannot remember it)
36
Urticaria cause
antigen-induced release of vasoactive mediators (histamine) from mast cells
37
Urticaria types
Mast cell-dependent, IgE-dependent
Mast cell-dependent, IgE-independent
Mast cell-independent, IgE-independent
38
Mast cell-dependent, IgE-dependent uticaria
occurs when
Occurs following exposure to antigen
39
Mast cell-dependent, IgE-independent uticaria
occurs when
Results from substances that directly incites degranulation of mast cells
not an actual allergy
40
Mast cell-independent, IgE-independent uticaria
is triggered by what?
Triggered by local factors increasing vascular permeability
41
Acute Eczematous Dermatitis subdivides into?
allergic contact dermatitis,
atopic dermatitis, drug-related eczematous dermatitis,
photoeczematous dermatitis, and primary irritant
dermatitis
42
Acute Eczematous Dermatitis cause
Typically results from T cell-mediated inflammatory
reactions (type IV hypersensitivity)
* Langerhans cells play a central role (especially in contact
dermatitis) as they antigen present to the T-cells that have the reaction
43
Acute Eczematous Dermatitis is also known as?
eczema
44
Erythema Multiforme
Self-limited hypersensitivity to certain infections and drugs that appears on the palms and soles
45
Chronic Inflammatory Dermatoses
Psoriasis, Seborrheic Dermatitis, Lichen Planus
46
Erythema Multiforme cause
Characterized by keratinocyte injury mediated by skin-homing CD8+ cytotoxic lymphocytes
47
Seborrheic Dermatitis cause
Precise etiology is unknown
Possible explanations include increased sebum production in response to androgens or a fungal infection
48
Psoriasis cause
an autoimmune basis
Sensitized CD4+ (Th1 and Th17) cells and CD8+ cytotoxic effector cells enter the skin and accumulate in the epidermis
causes keratinocyte proliferation & increased apoptosis
49
Lichen Planus cause
Unknown pathogenesis
Possibly an expression of altered androgens in basal epidermal cells or dermoepidermal junction causes a cell-mediated cytotoxic (CD8+) T-cell response
50
self limiting skin diseases
Erythema Multiforme and Lichen Planus (1-2 years)
51
Blistering (Bullous) Diseases
Pemphigus, Bullous Pemphigoid
52
Pemphigus cause
autoimmune
Caused by IgG autoantibodies against desmogleins --> disrupting intercellular adhesions, resulting in the formation of blisters
53
Bullous Pemphigoid cause
Caused by antibody to bullous pemphigoid antigen (BPAG) →
Prevents hemidesmosome from binding to basement membrane causing large blisters
54
Disorders of Epidermal Appendages
Acne vulgaris, Rosacea
55
Acne vulgaris (Acne) 4 factors that contrinbute to development
- keratin plug in the lower follicle blocking sebum outflow
- Hypertrophy of sebaceous glands under the influence of androgens
- Lipase-synthesizing bacteria (Propionibacterium acnes) colonizing the upper/mid hair follicle converting lipids to proinflammatory fatty acids
- Secondary inflammation of the involved follicle
56
Rosacea cause
Caused by high levels of the antimicrobial peptide, cathelicidin (mediator of the cutaneous innate immune response)
which causes an inflammed, red appearance of the skin
57
Infectious diseases
warts and imetigo
58
Verrucae (Warts) cause
human papillomaviruses (HPVs)
59
HPV strains 16 & 18
high risk for cancer
Produce E6 proteins that abolish p53 function
60
HPV strains 5 & 8
low cancer risk ones
Produce E6 proteins that don’t affect p53, rather interfere with
Notch signaling
61
Impetigo cause
Beta-hemolytic Staphylococcus aureus --> a bacterium that produces a toxin that cleaves desmoglein
62
tissue healing 2 components
regeneration and repair/scar formation
63
regeneration
stem cells proliferating to fill space injured (limited)
64
physiologic cell proliferation is considered
repair
65
pathologic cell proliferation is considered
cancer
66
liable cells examples
blood and external facing epithelium
67
liable cells development stage
Mitosis
68
what are liable cells
cells that continuously divide with a large pool of stem cells available
69
what are stable cells
dormant cells that minimally proliferate until stimulated
70
stable cells development stage
Go phase
71
Stable cells examples
parenchymal (solid tissue like liver)
endothelial cells, fibroblasts, smooth muscle
72
What happens when stable cells encounter excessive inflammation
they are unable to proliferate due tot heir need for stimulation and therefore cant regenerate (liver cirrhosis)
73
what are permanent cells
cells that do not proliferate
74
what type of repair dominates permanent cels
scar formation
75
what types of cells are permanent cells
nerves, muscle
76
what helps create scars
collagen and fibrin
77
What is maintained and what is different in scars
structure is different but function is maintained
78
Cell types for inflammation stage of healing
platelets
neutrophils
karyocytes
79
Cell types for the proliferate stage of healing
karyocytes
monocytes
on the later end: endothelial cells and fibroblasts
80
cell types for the remodeling stage of healing
endothelial cells and fibroblasts
81
what cells make cytokines and growth factors
paracrine cells
82
what do growth factors and cytokines do
stimulate mitosis, migration, differentiation, angiogenesis, contractility, fibrogenisis
stimm/ inhibit growth
inhibit apoptosis
83
transforming growth factor - alpha
increases hepatocytes and epithelial cells
84
vascular endothelial growth factor
VEGF
increases hepatocytes and epithelial cells
85
platelet derived growth factor
PDGF
chemotactic for healing
86
Fibroblast growth factor
FGF
chemotactic and angiogenisis
87
TGF- Beta
chemotactic for leukocytes and fibroblasts
decrease acute inflammation
88
Keratinocyte growth factor
KGF
increase keratinocytes
89
stages of wound helaing
hemostasis
inflammation
proliferation
90
hemostasis
plateket plug and clot formation create a scaffold for immune cells
via cytokine signalling
91
hemostasis: vessel status
vasoconstrict due to serotonin release
92
Inflammation 3 steps
neutrophilic debridement
histamine release (vasodilation)
macrophage phagocytosis
93
proliferation 4 aspects
reepithelialization
increase in granular tissue
increase in ECM
remodeling via collagen and myofibroblasts
94
reepithlialization cytokines
Interleukin 1 and TNF- alpha
95
how long does re-epithelialization last
2 days
96
granulation happens via what processes
angiogenesis &
fibroplasia: fill using collagen and ECM
97
granulation: fibroblast stimulated by what?
TGF-B
98
Proliferation of ECM can be what 2 types?
interstitial: between cells using glycoproteins, proteoglycans and collagen
basement: between epithelium and mesenchymal cells -> collagen laminin and proteoglycans
99
what do proteoglycans do
they are the gel that facilitate diffusion throughout the ECM
100
what do glycoproteins do
aid in cell to cell communication
101
collagen type 1
most common
adult
in all tissued
cord-like
tactile
102
collagen type 3
baby collagen
soft
laid down first in healing
103
remodeling: myofibroblasts
chains of fibrin that pull the edges of the wound
104
remodeling: collagen
take 3 weeks-3years
cross-linked net
105
wound closure: primary
stitch on top closes all layers
forming a minimal scar
106
would closure: secondary
deep layers clsoed
top layer left to hear into a larger scar
107
would closure: tertiary/ delayed primary intension
deep layers closed
superficial layers left open for up to 4 days allowing neutrophils to work
then closed with a primary stitch
108
would closure: delayed secondary intension
deep layer closed but allows for granular tissue to heal it instead of a primary stitch
109
aspects of wounds that inhibit healing
infection, ischemia, immunocompromised, malnutrition, limited vitamins, drugs, radiation, diabetes, increased age, smoking
110
poor wound healing: ischemia
can be due to lower circulation (cirrhosis or smoking)
decreased respiration
or local tension (too tight of a stitch)
111
poor wound healing: malnutrition
patients with burns experience high MBRs that must be met with adequate nutritional suppliemen
112
poor wound healing: decreased vitamins
vitamin C facilities collagen growth
113
poor wound healing: drugs
glucocorticosteriods decrease necessary inflammation needed for healing
114
Bad scar formation can cause? (2)
dehiscence (runpture)
ulceration
115
Keloid
healing outside the bounds of injury
excessive collagen type 1
can treat with steroid injection
116
Hypertrophic scar
healing inside the bounds of injury
excessive collagen type 1
can treat with steroid injection
117
hypertrophic granulation tissue
beefy, red appearance that prevents re-epithethelialization
must be scraped
118
exaggerated contraction
most common on palms/ soles and joints
healing created tighter skin due to poor positioning
may need skin graphs and stretching
119
Pressure ulcer
unrelieved pressure causes underlying tissue damage
120
Pressure ulcer stages
1- non blanch-able and intact skin
2 - partial thickness skin loss
3 - full thickness skin loss to subc layer
4- full thickness skin loss to muscle and bone
121
Stage 1 pressure ulcer
persistent redness on light skin
red/blue/purple on darker skintones
122
stage 3 pressure ulcer
deep crater w/wo undermining of adjacent tissue
can reach to the sub-c layer but not through
123
Stage 2 pressure ulcer
partial thickness skin loss (epidermis and/or dermis)
present as an abrasion/shallow crater
124
stage 4 pressure ulcer
extensive destruction, tissue necrosis and damage to muscle/bone
125
fungal infection - tinea
fungi in the skin is called dermatophytes. When these cause fungal disoeders they are called tinea
ex: tinea pedis -> athetes foot
126
how do we treat melanoma pathology wise
t-cells to attack cancers
127
pathology of melanoma
increasing cell proliferation (inhibit cell cycle inhibitors of CDK4) AND decreasing apoptotic factors (increase MDM2 to break down p53)
Patho 1&2
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