1
Q
What is the embyologic origin of the dermis?
A
Mesoderm
2
Q
What are the functions of the dermis?
A
- responsible for skin depth/density
- tensile strength (collagen, elastin)
- compressive resistance (proteoglycans, hyaluronan)
3
Q
What other roles do the dermis provide?
A
thermal regulation
water binding
cell growth, differentiation, and migration
wound repair and remodeling
protection against mechanical injury
4
Q
What makes up the ectracellular matrix (ECM) within the dermis?
A
1) insoluble fibers (collagen, elastin)
2) soluble polymers (proteoglycans, hyaluronan)
5
Q
What cells are housed within the dermis?
A
1) Resident cells (fibroblasts, macrophages, mast cells, melanocytes, dermal dendrocytes)
2) Transient cells (neuts, eos, lymphs, histiocytes, plasma cells)
6
Q
How is the scrotal dermis unique compared to the remaidner of the dermis?
A
Contains smooth muscle
7
Q
What are the two main regions in the dermis (in most species)?
A
1) Superficial dermis (papillary dermis - humans)
2) Deep dermis (reticular dermis - humans)
8
Q
What unique finding is present within the horse dermis?
A
Third dermal region - “Horse mirror”, aka Ross-Spiegel layer
- composed of collagen gibers in a tree-like arrangement
- shiny on gross exam
- present in the skin over rump, back, and uppder helf of chest
9
Q
What is the major cell type within the dermis, and what cell origin do they have?
A
1) Fibroblasts
2) mesenchymal origin
10
Q
What are the main functions of fibroblasts?
A
- major producer of ECM proteins (GAGs, glycoproteins, procollagen, elastin)
- degradation of matrix proteins
- symthesis of cell mediators needed for cell growth, differentiation, migration/inflammation (TFG-β, MMP-1)
11
Q
What forms the fibrous portion of the ECM?
A
1) Collagen
2) Elastin
12
Q
What special stain highlights collagen fibers?
A
Masson-trichrome
13
Q
What special stains highlight elastin on histopath (2)?
A
1) Verhoeff-van Gieson
2) acid orcein-Giemsa
14
Q
What substance makes up 75-80% of the dry weight of the dermis?
A
Collagen
15
Q
How many collagens have been identified?
A
28+
16
Q
Which types of collagen form fibrils?
A
I
III
V
XI
17
Q
What is the most abundant type of collagen in the adult dermis?
A
Type I
Type I = 80-87%
Type II = 10%
Type V = 3-5%
18
Q
What is the predominant type of collagen in fetal skin?
A
Type III
19
Q
What is the first collagen produced during wound healing?
A
Type III
20
Q
What types of collagen are found around blood vessels?
A
Types III and V
21
Q
What is the collagen that forms dermal microfibrils and what is its purpose?
A
1) Type VI
2) microfibrils stabilize and organize the larger fibrils of ECM
Typves VI, XII, and XIV support stability of larger, fibril-forming collagens
22
Q
What is the role of Types XII and XIV collagen?
A
- Fibril associated colalgens with interrupted triple helices (FACIT)
- Necessary for organization and stsability of fibril formoing collagens (I, II, III)
23
Q
What collagens are important for the BMZ (3)?
A
- IV (lattice for lamina densa)
- VII (anchoring fibrils)
- XVII (aka BPAG2/BP180 - transmembrane)
24
Q
Which amino acids are required for cross-linkage between collagen α chains?
A
Proline and hydroxyproline
(+ glycine)
25
What amino acid is essential to stabilize the helical structure of collagen?
Hydroxyproline
26
Type III has more of what amino acids when compared to Type I?
Hydroxyproline, glycine, cysteine
27
What amino acids are essential for cross-linking between collagen fibrils?
Lysine and hydroxylysine
28
Where does collagen synthesis begin, and where is it completed?
Begins in intracellular space
Completed extracellularly
29
What stimulates collagen synthesis?
vitamin C, TGF-β, IL-1, IL-4, IGF-1, IGF-2, superoxide generating system, bleomycin, PDGF
30
What inhibits collagen synthesis?
glucocorticolds, retinoids, vitamin D3, parathormone, PGE2, IFN-γ, pinicilliamine, minoxidil
31
Collagen synthesis - stimulator or inhibitor: vitamin C
Stimulator
32
Collagen synthesis - stimulator or inhibitor: TGF-B
Stimulator
33
Collagen synthesis - stimulator or inhibitor: IL-1
Stimulator
34
Collagen synthesis - stimulator or inhibitor: IL-4
Stimulator
35
Collagen synthesis - stimulator or inhibitor: IGF-1
Stimulator
36
Collagen synthesis - stimulator or inhibitor: IGF-2
Stimulator
37
Collagen synthesis - stimulator or inhibitor: superoxide generating systems
Stimulator
38
Collagen synthesis - stimulator or inhibitor: Bleomycin
Stimulator
39
Collagen synthesis - stimulator or inhibitor: PDGF
Stimulator
40
Collagen synthesis - stimulator or inhibitor: glucocorticoids
Inhibitor
41
Collagen synthesis - stimulator or inhibitor: retinoids
Inhibitor (+/-; can also stimulate in form of retinoic acid for quiescent cells)
42
Collagen synthesis - stimulator or inhibitor: Vitamin D3
Inhibitor
43
Collagen synthesis - stimulator or inhibitor: Parathormone
Inhibitor
44
Collagen synthesis - stimulator or inhibitor: Prostaglandin E2
Inhibitor
45
Collagen synthesis - stimulator or inhibitor: IFN-y
Inhibitor
46
Collagen synthesis - stimulator or inhibitor: D-penicillamine
Inhibitor
47
Collagen synthesis - stimulator or inhibitor: Minoxidil
Inhibitor
48
What amino acids are found within collagen fibers?
Glycine, proline, and hydroxyproline
49
What amino acids are required for cross-linking between collagen α-chains and act to stabilize the triple helix?
Proline, hydroxyproline
(also require glycine)
Hydroxyproline particularly important for stability
50
Which amino acids are required for cross linking between collagen fibrils?
Lysine and hydroxylysine
51
What enzyme is important for cross-linking colalgen fibrils, and what co-enzyme is required?
1) Lysyl oxidase
2) Copper
52
What does β-aminopropionitrile cause and why?
1) lathyrism
2) β-aminopropionitrile found in legumes, inhibits lysyl oxidase so cross linking collagen fibrils cannot appropriately occur
53
What compound inhibits lysyl oxidase action, and therefore cross-linking of collegn fibrils cannot occur?
β-aminopropionitrile
54
What is lathyrism?
defect in collagen synthesis (no cross-linking) that leads to bone and mesenchymal connective tissue defects
55
Collagen is degraded by what?
Collagenases --> matrix metalloproteinases (MMP)
56
What minerals does collagen require for proper function (2)?
1. Calcium
2. Zinc
57
What is gelatin?
denatured collagen
58
Collagen turnover is directly related to the amount of what within the urine and why?
1. The amount of hydrolysine and hydroxyproline in the urine
2. These AA's are relatively unique to collagen (elastin only ahs small amount of hydroxyproline)
59
What 4 requirements do prolyl and lysyl hydroxylase enzymes have to be able to function?
1. Oxygen
2. Ferrous iron
3. α-ketoglutarate
4. Vitamin C (reducing agent)
60
What is a clincal outcome of scurvy?
- Poor wound healing
- decreased tensile strength of connective tissue
61
How does hyperbaric oxygen therapy aid wound healing?
Increases activity of prolyl hydroxylase
62
What effect do steroids have on wound healing and why?
1) Decrease wound healing
2) because they inhibit prolyl hydroxylase
63
What is the rate limiting step of colalgen synthesis?
Hydroxylation of prolyl residues
64
What is a co-factor for glycosylation of hydroxylysyl groups?
Manganese
65
What enzyme is responsible for cross-linking collagen fibrils?
Lysyl oxidase
66
What mineral/element does lysyl oxidase require?
Copper
67
What inhibits lysyl oxidase?
β-aminoproprionitrile
68
What is lathyrism and what causes it?
1. defect in collagen synthesis (no cross-linking) that leads to bone and mesenchymal connective tissue defects
2. inhibition of cross-linking due to decreased lysyl oxidase activity becuase of inhibition by β-aminoproprionitrile
69
What tissues have the highest concentration of elastin?
aorta, arteries, lungs
70
What are the 3 types of elastic fibers found within the dermis?
1. Elastin
2. Eluanin
3. Oxytalan
71
What is the core of mature elastic fibers, and what is it surrounded by?
1. Core of elastin
2. Surrounded by microfibrils (fibrillins, fibulins) and type VI collagen
72
What types of elastic fibers anchor the superficial dermis and deep dermis?
Oxytalan
73
What type of elastic fibers anchors the superficial dermis to the BMZ?
Oxytalan
74
What type of elastic fiber has an arcade-like arrangement in the superficial dermis?
Elaunin
crosslinked to elastin with bundles of microfibrils
75
What is the precursor to elastin?
Tropoelastin
76
Where in cells is tropoelastin converted to elastin?
Within extracellular space (once secreted)
77
In addition to glycine, which 2 amino acids are important in the structure of elastin?
1. Valine
2. Proline
78
Why is elastin considered insoluble?
Due to cross-links formed by **desmosine** and **isodesmosine**
79
What is required for elastin cross-linkage to desmosine/isodesmosine to occur?
1) Lysyl oxidase (same as collagen)
2) Copper and Oxygen (same as collagen!!)
80
Summarize enzymes related to collagen and elastin synthesis and degradation and cofactor requirements (4 total):
1. Propyl and lysyl hydroxylases - allows for formation of hydroxyproline and hydroxylysine, requires oxygen, iron, α-ketoglutarate, vitamin C
2. Lysyl oxidase - crosslinking of collagen, requires copper, oxygen
3. MMP - degrades collagen, requires calcium and zinc
4. Elastase - degrades elastin, most are serine proteases, some need calcium
81
What stimulates elastin production?
TGF-β and IGF-1
82
Elastin synthesis - stimulate or inhibit: TGF-β
Stimulate
83
Elastin synthesis - stimulate or inhibit: IGF-1
Stimulate
84
What inhibits elastin production?
TNF-α, vitamin D3, colchicine
85
Elastin synthesis - stimulate or inhibit: TNF-α
Inhibit
86
Elastin synthesis - stimulate or inhibit: vitamin D3
Inhibit
87
Elastin synthesis - stimualte or inhibit: colchicine
Inhibit
88
What is the diffuse and filamentous matrix comprised of (3)?
1. glycoproteins
2. proteoglycans (PGs)
3. glycosaminoglycans (GAGs)
89
What does ground substance contain?
PGs and GAGs
90
What is the purpose/function of the ground substance?
1. Fills the space between fibrous matric and allows nutrients, electrolytes, cells to pass through the dermis
2. water storage and homeostasis
3. wound healing
4. resists compressive forces
91
What is a PG that binds to hyaluronic acid in the dermis?
Vesican
92
What is a PG that aggregates or "decorates" type I collagen?
Decorin
93
What PG is found intracellularly and where?
Serglycin --> eos and mast cells
94
What PGs are found on the cell surface?
syndecans and glypicans
95
List 5 GAGs
1. Heparan sufate
2. Chondroitin sulfate
3. Keratan sulfate
4. Dermatan sulfate
5. Hyaluronic acid
96
Which is the only GAG without a core protein?
Hyaluronic acid
97
What GAG has a high concentration in fetal skin and decreases with age?
Hyaluronic acid
98
What GAG allows for healing without scarring?
Hyaluronic acid
99
List 6 glycoproteins:
1. Fibrillin
2. Fibulin
3. Fibronectin
4. Vitronectin
5. Tenascin
6. Mucin
100
What is the main component of mucin?
Hyaluronic acid
101
What area of the body is mucin concentration highest?
Around appendages
102
What breed is associated with a higher dermal mucin content?
Shar Pei
103
What leads to a higher dermal mucin content in Shar Peis?
Increases hyaluron synthase
104
What color does mucin stain on H&E?
Blue
105
What special histopathologic stain can be used for mucin?
Alcian blue
106
Where are glycoproteins located and what can they do?
1. bound to collagen and elastin
2. modify cell-cell interactions, vascular permeability, development of collagen, and wound healing
form filamentous portion of ECM
107
What 3 inherited diseases of connective tissue are characterized by similar phenotype of excessive skin fragility and hyperextensibility?
1. Cutaneous asthenia
2. Ehlers-Danols
3. Dermatosparaxis (type of Ehlers-Danlos)
108
What us cutaneous asthenia?
Used in vet med to describe skin fragility/hyperextensibility phenotype
In humans - used for patients with both collagen and elastin affected disorders
109
What is dermatosparaxis?
- A specific type of EDS (VIIC) in humans
- Amino-ternminal of pro-collagen not removed because of defective protease activity
110
What gene mutation is associated with dermatosparaxis?
ADAMTS2
Protease responsible for cleavage of amin-terminals on pro collagen
111
What species has dermatosparaxis been reported in?
Cattle, sheep, cat (himalayan), dog (doberman)
Also humans
112
What stain can be used for patients with suspected Ehlers-Danlos Syndrome?
Masson-Trichrome
113
Other than the skin, what tissues can be affected in patients with cutaneous asthenia?
Ocular changes
ligaments
tendon
bone
blood vessels
114
What gene mutation is typically associated with cutaneous asthenia in vet med?
COL5A1 (classic EDS)
Others:
- Tenascin-1 (classic-like EDS; dog)
- ADAMTS2 (dermatosparaxis; cattle, sheep, dog, cats)
- PLOD1 (warmblood skin fagiliry syndrome; horses)
115
What breeds are overrepresented with HERDA?
Quarter Horses and crosses
Also seen in Appaloosas, Paints
116
What is the gene mutation for HERDA?
PPIB gene
Leads to abnormal protein cyclophilin B --> collagen folding altered
117
What is the mode of inheritance for HERDA?
Autosomal recessive
118
Is genetic testing available for HERDA?
yes - through UC Davis
119
What treatment can be pursued for cutaneous asthenia?
- husbandry: avoidance/reduction of trauma to skin
- +/- Vitamin C --> stimulator of collagen synthesis
120
What gene is responsible for Warmblood fragile foal syndrome?
PLOD1
121
What does the PLOD1 gene mutation result in for Warmblood Fragile Skin Syndrome?
lysyl hydroxylase does not function --> collagen not able to form triple helices
122
What is the mode of inheritance for Warmblood fragile skin syndrome?
Autosomal recessive
123
What is the prognosis associated with Warmblood fragile skin syndrome?
Poor
- nonviable or born stillborn
124
Is genetic testing avaialble for warmblood fragile skin syndrome?
Yes - UC Davis
125
How does glucocorticoid use lead to collagen deficiency?
inhibits prolyl hydroxylase --> triple helices not formed
126
How does solar elastosis result in reduced collagen and elastic fibers?
1. UV exposure reduces TGF-β (needed for procollagen secretion, also stimuates elastin production)
2. produces ROS --> leads to increased MMP (collagenases)
127
What does solar damage present on histopath?
pale, homogenous superficial collagen, can progress to fibrosis; collagen and elastin thickened, wavy, basophilic fibers
128
Whatis scleroderma?
Thickened deep dermal collagen
129
Species in which scleroderma is seen:
Horses
Humans
130
Name for localized scleroderma
Morphea
131
Besides skin, what other organs are affected by generalized scleroderma that results in progressive fibrosis?
Lungs, GI tract, kidneys, and heart
132
What conditions can lead to excessive mucin production (6)?
1. Hypothyroidism
2. Acromegaly
3. DLE
4. Dermatomyositis
5. Alopecia mucinosa
6. Idiopathic form (Shar-Peis)
133
What is the cause of excess lucin production in Shar-peis?
Increased hyaluron synthase
134
What can you use to treat idiopathic mucinosis?
Corticosteroids
(would inhibit hyaluron synthase)
135
Marfan Syndrome species and gene in vet med:
Cattle (Limousine crossbred calves)
Fibrillin-1 gene mutation
136
Gene associated with nodular dermatofibrosis:
Folliculin gene (FLCN)
137
Breed in dogs associated with dermatofibrosis?
GSD
138
Comorbidities seen in dogs with nodular dermatofibrosis?
Renal Cystadenocarcinoma
+/- Uterine leimyomas
139
ACVD Boards 2025
flashcards
Decks in class (22)
# Cards
-
Ontogeny40
-
Melanogenesis132
-
Hair Follicle and Adnexa243
-
Dermis139
-
Cornification and Keratinization163
-
Adhesion Molecules30
-
BMZ, Pemphigus and Pemphigoid Complex156
-
Immunology and Cytokines150
-
Hypersensitivities95
-
ICADA Genetic and Environmental Factors, Allergens in cAD47
-
ICADA Skin Barrier and Host-micro-organism interaction31
-
ICADA Innate Immunity, Lipid Metabolism, Nutrition37
-
Psychoneurodermatology126
-
Malassezia and Candida52
-
Dermatophytosis83
-
Other Fungal Disease54
-
Endocrinopathy125
-
Pharmacology215
-
Staph and Resistance Mechanisms68
-
Dermatohistopathology12
-
Equine Allergy77
-
Leishmania and Atypical Infection4
