Dermis, adnexa and collagen Flashcards
1
Q
Describe the secretory function of sebaceous glands
A
Holocrine- cells burst and release full contents into ducts
2
Q
Describe the secretory function of eccrine (atrichial) sweat glands
A
Merocrine- secrete product via exocytosis
3
Q
Where do sebaceous glands empty their contents?
A
Into the hair follicle canal
4
Q
Where do epitrichial glands empty their contents?
A
Into the hair follicle canal
5
Q
Where do eccrine (atrichial) glands empty their contents?
A
Directly onto the skin
6
Q
On what parts of the body are sebaceous glands larger and more numerous?
A
Mucocutaneous junctions, interdigital spaces, rump, chin, dorsal tail
7
Q
What 2 parts of the body do NOT contain sebaceous glands?
A
Paw pads, nasal planum
8
Q
What are the two types of sweat glands?
A
Epitrichial, atrichial (eccrine)
9
Q
Define merocrine secretion
A
Secretory vesicles travel to apical surface of cell, fuse with plasma membrane, and release secretion into extracellular space (no part of cell is lost)
10
Q
Define apocrine secretion
A
Secretory products accumulate at the apical portion of the cell and are released by pinching off some of the plasma membrane and cytoplasm (top of the cell is lost)
11
Q
Define holocrine secretion
A
Secretory products accumulate at apical end of cell and the cells undergoes apoptosis and disintegration, releasing the secretory products and cell debris (whole cell is lost)
12
Q
What is contained within horse sebum that isn’t found in other species’ sebum?
A
Lactones
13
Q
What is the effect of estrogens on sebaceous glands?
A
Involution
14
Q
What is the effect of glucocorticoids on sebaceous glands?
A
Involution
15
Q
What is the effect of androgens on sebaceous glands?
A
Hypertrophy/hyperplasia
16
Q
What is the effect of retinoids on sebaceous gland secretion?
A
Reduced sebum production
17
Q
Describe the secretion of epitrichial sweat glands
A
Merocrine (though historically classified as apocrine, this is incorrect)
18
Q
Where are epitrichial sweat glands found in the skin?
A
All haired skin, adjacent to primary hair follicles and deep to sebaceous glands
- not present on paw pads or nasal planum
19
Q
What is the relationship between epitrichial sweat gland size and hair density?
A
These glands are larger in areas with less hair
20
Q
On what parts of the body are epitrichial sweat glands larger and more numerous?
A
Mucocutaneous junctions, interdigital spaces, chin, rump, dorsal tail (same as sebaceous glands)
21
Q
What glands are lacking in rodents and ferrets?
A
Epitrichial sweat glands
22
Q
Where are epitrichial sweat glands found in rabbits?
A
Around the lips ONLY
23
Q
What glands are lacking in horses?
A
Atrichial sweat glands
24
Q
What type of gland are the circumanal/hepatoid glands?
A
Modified sebaceous glands
25
What is the primary sweat gland in horses?
Epitrichial gland
26
Which signals promote the development of sebocytes/sebaceous glands from stem cells?
Shh, Myc
27
Which signal inhibits the development of sebocytes/sebaceous glands?
Wnt
28
What special stain could be used to highlight lipid?
Oil red O
29
What receptors on sebaceous glands help accumulate lipid from the circulation?
LDL (low density lipoprotein), FATP4 (fatty acid transporter 4)
30
What type of gland is affected in equine anhidrosis?
Epitrichial sweat glands
31
What stain could you use to highlight epitrichial gland ducts and acini?
Cytokeratin
32
What is the mode of inheritance of sebaceous adenitis in poodles and Akitas?
Autosomal recessive
33
What conditions could potentially be associated with sebaceous adenitis?
Leishmaniasis
Hypothyroidism
34
What equine breeds are at increased risk of anhidrosis?
Warmbloods
Thoroughbreds
35
Describe the pathogenesis of equine anhidrosis
Continuously high levels of epinephrine leads to desensitization and downregulation of aquaporin-5 receptors and degeneration of secretory cells
36
What class of antibiotics has been associated with anhidrosis in horses?
Macrolides (especially erythromycin)
37
How do you test for anhidrosis in horses?
Intradermal injection of epinephrine or another beta-2 agonist (i.e. terbutaline)--> anhidrotic horse only sweats at the highest concentration(s) and only several hours after injection
38
What is the developmental origin of the dermis?
mesoderm
39
Where is the dermis the thickest?
Haired skin
40
What are the primary cells that form dermal fibers?
Fibroblasts
41
What type of fiber makes up the majority of the dermal ECM?
Collagen
42
What special stain would highlight collagen?
Maisson trichrome (collagen stains blue)
43
What collagen types predominate in the dermis?
1, 3, 5
44
What type of collagen is prevalent in wound healing and in fetal skin?
Type III
45
What type of collagen is a major component of anchoring fibrils?
Type VII
46
Where does collagen synthesis begin?
Within fibroblasts (on the rough ER)
47
What occurs to proline and lysine in the rough ER?
They are hydroxylated into hydroxyproline and hydroxylysine
48
What enzymes hydroxylate proline and lysine?
Prolyl and lysyl hydroxylase
49
What factor is the hydroxylation of proline and lysine dependent upon?
Ascorbic acid (vitamin C)
50
What occurs to hydroxylysine once it is released from the rough ER?
it is glycosylated
51
In what form is collagen secreted out of the fibroblast?
Pro-collagen
52
What is the final step in pro-collagen formation?
3 pro-alpha chains twist to form a triple helix
53
What does collagen become right after it is secreted as procollagen?
Tropocollagen
54
What enzyme is critical to transform procollagen to tropocollagen?
Procollagen peptidase
55
What enzyme links tropocollagen molecules to form collagen fibrils?
Lysyl oxidase
56
What metal is necessary for normal functioning of lysyl oxidase?
Copper
57
What protein is excreted in urine and can serve as a marker of collagen degradation?
Hydroxyproline
58
What enzyme involved in collagen synthesis is inhibited by glucocorticoids?
Prolyl hydroxylase
59
What is the effect of TGF-B on collagen synthesis?
Stimulatory
60
What is the effect of IL-1 on collagen synthesis?
Stimulatory
61
What is the effect of bleomycin on collagen synthesis?
Stimulatory
62
What is the effect of IGF 1+2 on collagen synthesis?
Stimulatory
63
What is the effect of vitamin D3 on collagen synthesis?
Inhibitory
64
What is the effect of PGE2 on collagen synthesis?
Inhibitory
65
What is the effect of IFN-gamma on collagen synthesis?
Inhibitory
66
What is the effect of TNF-a on collagen synthesis?
Inhibitory
67
What special stain can highlight elastin?
Verhoeff van Gieson
68
What special stain can highlight reticulin fibers?
Silver
69
What is a proteoglycan?
A protein covalently linked to a glycosaminoglycan
70
Name 4 types of glycoproteins
Fibronectin
Proteoglycan
Tenascin
Mucin
71
What enzyme has increased synthesis by dermal fibroblasts, resulting in increased mucin in Shar Peis
Hyaluronan synthase 2
72
What is the major proteoglycan found in the dermis?
Versican
73
What cells synthesize glycoproteins in the dermis?
Fibroblasts
74
Which IHC stains can distinguish dermal dendrocytes from Langerhans cells?
Dermal dendrocytes are CD4+, CD90+
75
What proteases may be contained within mast cells?
Tryptase, chymase, or both
76
What are the primary cell types in the dermis?
Fibroblasts
Dermal dendrocytes
Melanocytes
Mast cells
Lymphocytes (low #)
77
What is the major type of vessel in the dermis?
Post-capillary venules
78
What is the physiologically reactive segment of the dermal microcirculation?
Post-capillary venules
79
Where would you find Weibel-Palade bodies?
Within the endothelial cell cytoplasm
80
What is the function of Weibel-Palade bodies?
Store VWF and P-selectin
81
What is the function of pericytes?
Contractile cells which regulate capillary flow
82
What are the slow-adapting mechanoreceptors in the skin?
Tylotrich pads
Ruffini corpuscle
Merkel cells
83
What are the fast-adapting mechanoreceptors in the skin?
Meissner's corpuscle
Pacinian corpuscle
Tylotrich HAIR
84
What does a Meissner's corpuscle sense?
low-frequency vibration
touch
85
What does a Pacinian corpuscle sense?
High-frequency vibrations
touch
86
What does a Ruffini corpuscle sense?
Stretch
87
What does a Merkel cell sense?
Pressure
Edges
Curves
88
What is mutated in Ehlers-Danlos syndrome?
Type I or III collagen
89
What is the genetic defect in Ehlers-Danlos syndrome?
Lysyl hydroxylase
90
What condition is characterized by cigarette paper scars?
Ehlers-Danlos/HERDA
91
How do you calculate the skin extensibility index?
(Vertical height of skin fold/body length) x 100
92
What skin extensibility index is abnormal in dogs?
>14.5%
93
What skin extensibility index is abnormal in cats?
>19%
94
True or false: HERDA skin does not heal readily
False (but causes cigarette paper scars)
95
What special stains can be used to highlight mucin?
Alcian Blue
PAS
Mucicarmine
96
What are the components of the extracellular matrix?
Collagen
Elastin
Microfibrillar proteins
Fibronectin
Proteoglycans
97
What is the key role of collagen in the dermis?
Tensile strength (resistance to stretch)
98
What is the amino acid structure of type I collagen?
Glycine-X-Y (X usually proline, Y usually hydroxyproline)
99
How does the AA content of type III collagen differ from that of type I?
Type III collagen has a cysteine residue in addition to glycine and lots of hydroxyproline
100
What type of collagen is found within hemidesmosomes and anchoring filaments, attaching the basal keratinocyte to the basement membrane?
Collagen XVII (BPAG2)
101
What is another name for collagen XVII?
BPAG2
102
What type of collagen forms anchoring fibrils?
Type VII
103
What 2 collagens are necessary for cohesion of the epidermis and dermis?
Collagen VII - attaches BM to dermal ECM
Collagen XVII - attaches basal keratinocytes to lamina densa
104
What molecule is crucial for the folding of collagen and its triple helix structure?
Hydroxyproline (specifically trans-4-hydroxy-1-proline)
105
What enzymes cleave the terminal ends of procollagen to form tropocollagen?
Procollagen N-proteinase (removes amino terminal)
Procollagen C-proteinase (removes carboxy terminal)
(procollagen peptidases)
106
What is the mutation in HERDA?
missense mutation in cyclophilin B (PPIB gene) --> glycine is substituted to arginine
--PPIB is important for normal collagen folding
107
How does UV radiation impact HERDA?
UV --> upregulation of collagenase genes (esp matrix metalloproteinase 1) --> thin skin especially on dorsum
108
What is the effect of retinoids on collagen production?
Inhibitory OR stimulatory
109
What mineral do matrix metalloproteinases require for their activity?
Calcium
110
What collagens does MMP-1 break down?
I, III, VII
111
What are desmosines?
Covalent cross-links that make elastic fibers insoluble
112
Is hydroxylysine present in elastic fibers?
No
113
What is the major function of the dermal ground substance?
Hydration
114
What do glycosaminoglycans bind in order to provide hydration?
Ions and water
115
Where would perlecan be found in the skin?
All basement membranes
116
What is the specific mutation in the autosomal dominant form of Ehlers-Danlos in dogs?
COL5A1
117
What is the mutation in dermatosparaxis?
ADAMTS-2 (aka procollagen N-proteinase)
118
What element do the matrix metalloproteinases contain?
Zinc
119
Which MMPs degrade collagen I to collagen III?
Interstitial collagenases (MMP-1, MMP-8, MMP-13)
120
What is the effect of IL-1 on MMP activity?
Increases MMP
121
In which vessels of the microcirculation do inflammatory cells migrate out of the vasculature and into tissue?
Post-capillary venules
122
In what type of vessels would you find tight junctions?
Arterioles and capillaries
123
What type of junction is present in postcapillary venules?
Adherens junctions (allows for passage of macromolecules)
124
Are sinus hairs slow-adapting or fast-adapting?
Slow-adapting
125
Besides the face, where would you find vibrissae in cats?
Palmar aspect of carpus
126
What type of mechanoreceptor is located near a sinus hair follicle?
Pacinian corpuscle
127
What types of nerves detect painful touch?
High-threshold C fibers and Alpha-delta nerve fibers
128
What type of nerve fibers are the largest and most heavily myelinated?
Alpha-beta/type II fibers
129
What is the most abundant type of somatosensory neuron?
C/type IV fibers
130
What type of somatosensory neuron is unmyelinated?
C/type IV
131
What type of nerve fiber responds to pruritogens?
C/type IV
132
What type of nerve fiber has a slow conduction velocity?
C/type IV
133
Through which part of the spinal cord do afferent sensory nerves travel to deliver pain/pruritus signals?
Dorsal root ganglion
134
How does nerve growth factor promote itch?
It upregulates other neuropeptides (esp substance P and TRPV1)
135
What type of opioids induce itch?
mu-receptor agonists
136
What type of opioids reduce itch?
kappa-receptor agonists (and mu antagonists)
137
What cells produce kallikreins?
WBC
KCs
Mast cells
Endothelial cells
Platelets
138
What type of cell secretes TSLP?
KCs
139
What type of T-cell response is promoted by TSLP?
Th2
140
What cytokines are known to be pruritogens?
IL-2
IL-4
IL-13
IL-31
IL-33
TSLP
141
What cells produce PGE2?
nerve fibers, KCs, mast cells
142
What viral disease in cats is associated with facial pruritus?
Herpes
143
What dog breeds are predisposed to inherited sensory neuropathies resulting in self-mutilation?
English Pointers (paws), Long-haired dachshunds (penis)
144
What neuropathic disorders could cause tail-biting in dogs?
Cauda equina syndrome
Tail dock neuroma
Lumbosacral stenosis
145
What cat breed is predisposed to tail-sucking?
Siamese
146
What breed is predisposed to flank sucking?
Doberman
147
Is chronic itch primarily histaminergic or non-histaminergic?
Non-histaminergic (so antihistamines don't work very well)
148
Edema in urticaria is limited to what layer of the skin?
Dermis
149
Besides skin hyperextensibility, which other clinical signs might be seen with Ehlers-Danlos syndrome?
Joint laxity
150
How does cutis laxa differ from Ehlers-Danlos clinically?
Ehlers-Danlos: fragile skin, maintains elastic recoil
Cutis laxa: flaccid but no cutaneous fragility, lacks elastic recoil
151
What type of stain will highlight elastic fibers in the dermis?
Verhoeff
152
What type of stain will highlight elaunin AND elastic fibers in the dermis?
Weigert
153
What type of stain will highlight elaunin, elastic, AND oxytalan fibers in the dermis?
Oxidized Weigert
154
What mutation occurs in Marfan syndrome in cattle?
FBN1 (fibrillin 1)
155
What is the main clinical difference between Ehlers-Danlos and cutis laxa?
Ehlers-Danlos skin: hyperextensible skin which snaps back when tented
Cutis laxa: excessive skin and hyperextensible but will not snap back when tented
156
This is a picture from a draft horse. Based on the radiograph, what is a top differential?
Chronic progressive lymphedema
157
Describe the pathogenesis of solar elastosis
UV exposure --> cytokine expression --> neutrophil infiltration --> MMP and elastase release and ECM damage --> attempted repair via secretion of elastic fiber components
158
What is the cause of erythema ab igne?
Chronic exposure to radiant heat source
159
Does erythema ab igne usually ulcerate, crust, and/or scar?
No (think vasculopathy or burn if you see these signs)
160
True or false: hepatoid glands are not present in cats
True
161
What gene is mutated in Shar Pei mucinosis?
HAS2
162
What gene is mutated in Ehlers-Danlos syndrome in cats?
COL5A1
163
Which proteinase resides within neutrophil granules and degrades predominantly collagen I and III upon release?
MMP-8
164
What cytokine is a major stimulator of elastin production?
TGF-B
165
During the formation of a proteoglycan, which amino acid residue does the glycosaminoglycan bind to within the protein core?
Serine
166
True or false: epitrichial glands are involved in thermoregulation
False
167
What is the necessary signal pathway for development of sebocytes?
SOX9
168
What stain could you use to highlight amyloid?
Congo Red
