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83 Cards in this Set
- Front
- Back
Collagens are responsible for the tensile strength of the dermis and are composed of triple helix a- chains. What is the amino acid sequence for collagen? |
Gly-x-y
high numbers of proline and hydroxyproline in the X and Y positions
hydrogen bonds between hydroxyproline give collagen strength |
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What percentage of collagen makes up the dry weight of the dermis? |
75% |
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Most collagens in the skin are made by dermal fibroblasts.
EXCEPT!
Epidermal keratinocytes and fibroblasts systhesize... |
7 & 17 are synthesized by epidermal keratinocytes and fibroblasts |
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Most collagens in the skin are made by dermal fibroblasts.
EXCEPT!
Endothelial cells synthesize... |
8 & 18 are synthesized by endothelial cells |
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Hightlights of collagen synthesis? |
1. pre-pro a chains synthesized
2. hydroxylation/ glycosylation
3. disulfide bonds between hydroxyl groups
4. triple helix formation of procollagen
5. cleavage of N and C terminus
6. assembly into fibrils with covalent crosslinks |
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In collagen synthesis, ascorbic acid is a co factor for... |
Vit C is required to hydroxylate proline
all the pro's take Vit C! |
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In collagen synthesis, copper is a co factor for... |
Copper is required to hydroxylate lysine |
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What disorder is associated with a defect in lysyl hydroxylase? |
EDS- kyphoscoliosis (PLOD gene) |
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What disorder is associated with a defect in Procollagen N- proteinase gene ? What is this gene called? |
ADAMTS-2
EDS- DERMATOSPARAXIS
Adam is a little sprite (fairy?) |
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What disorder is associated with a mutation in the amino terminal propeptide cleavage sites of COL1A1 or COL1A2? |
EDS- arthrochalasia
arthro <-> ortho <-> bones, type I collagen |
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What is the periodicity of the cross banding in dermal collagen? |
64nm |
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Which are the fibril forming collagens? |
I, II, III, V, XI |
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Which are the basement membrane collagens? |
IV
(remember the vascular basement membrane is VIII, XVIII) |
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What are the microfibril forming collagens? |
VI |
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What are the anchoring fibrils? |
VII |
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These collagens are found where:
I II III IV V XX XXII XXV |
I- skin/bone II- CT, cartilage, vitreous humor III- vascular, lung, skin IV- BM V- skin XX- skin, cornea, TENdon XXII- hair XXV- brain, neurons |
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Collagen I --> where is it? What disease is it associated with? |
Fibril forming collagen found in skin, bone
mutated in EDS arthrochalasia and OI |
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Collagen II --> where is it? What disease is it associated with? |
Fibril forming collagen found in cartilage and vitreous humor
antibodies to collagen II found in relapsing polychondritis |
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Collagen III --> where is it? What disease is it associated with? |
Fibril forming collagen found in GI, vascular structures, fetal skin
mutated in EDS vascular type |
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Collagen IV --> where is it? What disease is it associated with? |
Found in lamina densa of BM skin and glomerulus of kidney
Mutated in Alport's syndrome, Goodpasture's syndrome |
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Collagen V --> where is it? What disease is it associated with? |
Ubiquitous in connective tissue
MC cause of classic EDS (Classic = Cinco) |
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Collagen VI-- What disease is it associated with? |
Collagen VI is associated with Ullrich disease (muscular dystrophy) |
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Collagen VIII and XVIII are found where? |
vascular basement membranes |
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Collagen VII is found where? Associated diseases? |
anchoring fibril that attaches to the BM
diseases- Dystrophic EB, bullous SLE, EBA |
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Collagen XVII is also known as? Associated diseases? |
Collagen XVII is aka BPAg2, BP180
diseases: junctional EB non-herlitz, BP, linear IgA, HG, cicatricial pemphigoid
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Look up the BM pictures. |
DO IT NOW. |
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Which of these up regulate collagen synthesis?
TGFB ATII Glucocorticosteroids Retinoids MMPs Hyperthyroidism |
UP- TGFB, ATII, Retinoids |
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Which of these down regulate collagen synthesis?
TGFB ATII Glucocorticosteroids Retinoids MMPs Hyperthyroidism |
Glucocorticoids, MMPs, hyperthyroidism |
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MMPs are a group of enzymes that are capable of degradation of the ECM. What co factor do they require? |
ZINC AND CALCIUM |
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Most elastic tissues by weight is found in? |
Aorta |
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Basic molecular unit of elastin? What is unique about it? |
Tropoelastin
less hydroxyproline than collagen contains desmosine and isodesmosine (unique to elastin) |
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If your body lacks copper, what portions of the ECM can't it produce? |
COLLAGEN or ELASTIN |
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Orientation of oxytalan and elaunin? |
oxytalan- perpendicular
elaunin- parallel |
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Defective fibrillin 2? |
congenital contractural arachnodactyly |
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GAGs covalently bound to a core protein? |
proteoglycan |
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Most ubiquitous protein-free GAG? |
Hyaluronic acid |
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4 different types of GAGs that form proteoglycans? |
chondroitin sulfate dermatan sulfate keratan sulfate heparan sulfate |
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Versican is the most important proteoglycan, causes tautness of the skin, forms complex with hyaluronic acid. What is versican made of? |
Chondroitan and dermatan |
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What is perlecan and where is it found? |
proteoglycan- found in BM |
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Mutation in laminin 5? Antibodies to laminin 5? |
Laminin 5 aka Laminin 332
Mutation- dystrophic EB Antibodies- antiepiligrin cicatricial pemphigoid |
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Mutation of COL1? |
EDS Arthrochalasia --> hyperextensible skin, fragility, joint hypermobility (multiple joint dislocations), scoliosis |
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Mutation of COL3? |
EDS Vascular --> fragile skin (collagen 3 is in fetuses, and fetuses have fragile skin), bruising, arterial fragility, organ (uterine) rupture, most people will have a life threatening complication by 40 |
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Mutation of COL5? |
EDS Classic --> hyperextensible skin, fragility, joint hypermotility |
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Mutation of Tenascin X? |
EDS Hypermobility --> joint hyperextensibility, otherwise benign |
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Mutation of lysyl hydroxylase (PLOD1)? |
EDS Kyphoscoliosis --> kyphoscoliosis, muscle weakness, lung disease, joint laxity, ocular fragility |
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Mutation of Dermatan -4- Sulfotransferase? |
EDS Musculocontractural --> craniofacial abnormalities, joint contractures, wrinkled palms |
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Mutation of ADAMTS2? |
EDS Dermatosparaxis --> fragile saggins skin, easy bruising, hernias
Adam is a sprite |
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Aside from the lax, redundant skin in cutis laxa, what are some of the other symptoms? |
pulmonary emphysema, pulmonary artery stenosis, bladder diverticula |
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Mutation in ATP7A? |
Occipital Horn Syndrome
lax skin, tortuous arteries, joint hypermobility, occipital calcifications
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Defect in Marfans syndrome? Skin findings? |
Fibrillin 1
striae distensae, elastosis perforans serpiginosa, tall stature, pectus excavatum, high arched palate, aortic anuerysm, up/out dislocation of lens, spontaneous PTX |
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Deficiency in homocysteinuria? |
CYSTATHIONINE BETA SYNTHEASE |
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Yellow papules on the chest and neck, angiod streaks in eye, lax skin... mutation? |
Pseudoxanthoma elasticum
mutation of ABCC6 |
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Mutation in collagen 7? Autoantibodies to collagen 7? |
Mutation- dystrophic EB
Antibodies- EBA SLE |
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Antibodies to ECM-1? |
lichen sclerosis |
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Mutations of ECM-1? |
lipoid proteinosis |
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Perforating disorders are broken into: 1. 2. 3. |
Perforating disorders are broken into: 1. acquired perforating dermatosis 2. elastosis perforans serpingosa 3. reactive perforating collagenosis |
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Acquired perforating dermatosis are most common in what populations? |
10% prevalence in renal dialysis patients, can also see in DM, multiparous black women on belly
Kyrles disease |
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Most effective therapy for acquired perforating dermatosis? |
UV light |
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Reactive perforating collagenosis is most common in which populations? |
begins in childhood after superficial trauma --> patients develop keratotic papules that spontaneously resolve over 6-8 weeks |
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With Verhoeff van Gieson stain, what color are collagen fibers? |
RED |
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With Verhoeff van Gieson stain, what color are elastin fibers? |
BLACK |
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Elastosis perforans serpiginosa is most commonly assoicated with what disorders? |
RAP MOPED!!!!
Rothmund thompson- RECQL4 poikiloderma, cataracts, bone defects, absent thumbs, hypodontia
Acrogeria- old extremities
Penicillamine- in wilsons
Marfans- fibrillin 1, aortic dissection
OI- COL1
Pseudoxanthoma elasticum- ABCC6 causes fragmentation and mineralization of elastic fibers of skin, eyes, BV, see popcorn on path
ESD
Downs syndrome |
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What underlying disorder? |
Kyrle's disease, most common on legs
possible underlying renal disease, DM, multiparous black female |
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The major component of the anchoring filaments is:
uncein plectin a6b4 integrin laminin 5 collagen type IV |
laminin 5 aka epiligrin |
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T/F
Elastic fibers are 90% elastin wrapped in fibrillin? |
TRUE- form 4% of the dry weight of the skin |
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Desmosine and isodesmosine are typical AA found in:
collagen fibers anchoring fibrils elastic fibers heparan sulfate anchoring plaques |
elastic fibers |
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Dystrophic EB results from a mutation in collagen type: |
VII |
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What collagen is mutated in osteogenesis imperfecta? |
collagen 1 |
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Granulation tissue primarily contains:
collagen I collagen II collagen III collagen IV fibrin |
collagen III
it begins to form 4 days after injury |
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The formation of granulation tissue depends of the presence of:
neuts fibronectin collagen I platelets collagen IV |
fibronectin- granulation tissue forms 4 days after injury |
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homocystinuria has abnormal crosslinking of collagen because of a mutation in : |
cystathione synthase |
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Type VII collagen is found in anchoring fibrils and in:
fetal skin bone amnion aorta BV |
amnion, ew |
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Anchoring fibrils are primarily composed of? Mutation? Immuno? |
Collagen VII
Mutated- dystrophic EB Immuno- EBA and BULLOUS SLE |
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The main permeability barrier in the lamina densa is: |
heparan sulfate proteoglycan |
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Retinoids upregulate transcription of which types of collagen? |
1 & 7 |
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Fragmentation and/or loss of elastic fibers is not seen in:
cutis laxa marfans anetoderma pseudoxanthoma elasticum buschke ollendorf syndrome |
buschke ollendorf syndrome |
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What percent of the dry weight of skin is elastin? |
4% |
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Do elaunin fibers run:
parallel to the superficial papillary dermis parallel to the reticular dermis perpendicular to the superficial papillary dermis perpendicular to the reticular dermis
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elaunin fibers run parallel to the reticular dermis |
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Most collagens in the skin are synthesized by: |
dermal fibroblasts |
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Collagens 7 & 17 are synthesized by |
epidermal keratinocytes and fibroblasts |
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Collagens 8 & 18 are synthesized by |
endothelial cells |
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co factor required to hydroxylated proline? |
vitamin C |
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co factor required to hydroxylate lysine? |
copper |