Bafl Exam 2: Biology Of The Extracellular Matrix And Perforating Disorders

Front 1

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?

Back 1

Gly-x-y

high numbers of proline and hydroxyproline in the X and Y positions

hydrogen bonds between hydroxyproline give collagen strength

Front 2

What percentage of collagen makes up the dry weight of the dermis?

Back 2

75%

Front 3

Most collagens in the skin are made by dermal fibroblasts.

EXCEPT!

Epidermal keratinocytes and fibroblasts systhesize...

Back 3

7 & 17 are synthesized by epidermal keratinocytes and fibroblasts

Front 4

Most collagens in the skin are made by dermal fibroblasts.

EXCEPT!

Endothelial cells synthesize...

Back 4

8 & 18 are synthesized by endothelial cells

Front 5

Hightlights of collagen synthesis?

Back 5

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

Front 6

In collagen synthesis, ascorbic acid is a co factor for...

Back 6

Vit C is required to hydroxylate proline

all the pro's take Vit C!

Front 7

In collagen synthesis, copper is a co factor for...

Back 7

Copper is required to hydroxylate lysine

Front 8

What disorder is associated with a defect in lysyl hydroxylase?

Back 8

EDS- kyphoscoliosis (PLOD gene)

Front 9

What disorder is associated with a defect in Procollagen N- proteinase gene ? What is this gene called?

Back 9

ADAMTS-2

EDS- DERMATOSPARAXIS

Adam is a little sprite (fairy?)

Front 10

What disorder is associated with a mutation in the amino terminal propeptide cleavage sites of COL1A1 or COL1A2?

Back 10

EDS- arthrochalasia

arthro <-> ortho <-> bones, type I collagen

Front 11

What is the periodicity of the cross banding in dermal collagen?

Back 11

64nm

Front 12

Which are the fibril forming collagens?

Back 12

I, II, III, V, XI

Front 13

Which are the basement membrane collagens?

Back 13

IV

(remember the vascular basement membrane is VIII, XVIII)

Front 14

What are the microfibril forming collagens?

Back 14

VI

Front 15

What are the anchoring fibrils?

Back 15

VII

Front 16

These collagens are found where:

I

II

III

IV

V

XX

XXII

XXV

Back 16

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

Front 17

Collagen I --> where is it? What disease is it associated with?

Back 17

Fibril forming collagen found in skin, bone

mutated in EDS arthrochalasia and OI

Front 18

Collagen II --> where is it? What disease is it associated with?

Back 18

Fibril forming collagen found in cartilage and vitreous humor

antibodies to collagen II found in relapsing polychondritis

Front 19

Collagen III --> where is it? What disease is it associated with?

Back 19

Fibril forming collagen found in GI, vascular structures, fetal skin

mutated in EDS vascular type

Front 20

Collagen IV --> where is it? What disease is it associated with?

Back 20

Found in lamina densa of BM skin and glomerulus of kidney

Mutated in Alport's syndrome, Goodpasture's syndrome

Front 21

Collagen V --> where is it? What disease is it associated with?

Back 21

Ubiquitous in connective tissue

MC cause of classic EDS (Classic = Cinco)

Front 22

Collagen VI-- What disease is it associated with?

Back 22

Collagen VI is associated with Ullrich disease (muscular dystrophy)

Front 23

Collagen VIII and XVIII are found where?

Back 23

vascular basement membranes

Front 24

Collagen VII is found where? Associated diseases?

Back 24

anchoring fibril that attaches to the BM

diseases- Dystrophic EB, bullous SLE, EBA

Front 25

Collagen XVII is also known as? Associated diseases?

Back 25

Collagen XVII is aka BPAg2, BP180

diseases: junctional EB non-herlitz, BP, linear IgA, HG, cicatricial pemphigoid

Front 26

Look up the BM pictures.

Back 26

DO IT NOW.

Front 27

Which of these up regulate collagen synthesis?

TGFB

ATII

Glucocorticosteroids

Retinoids

MMPs

Hyperthyroidism

Back 27

UP- TGFB, ATII, Retinoids

Front 28

Which of these down regulate collagen synthesis?

TGFB

ATII

Glucocorticosteroids

Retinoids

MMPs

Hyperthyroidism

Back 28

Glucocorticoids, MMPs, hyperthyroidism

Front 29

MMPs are a group of enzymes that are capable of degradation of the ECM. What co factor do they require?

Back 29

ZINC AND CALCIUM

Front 30

Most elastic tissues by weight is found in?

Back 30

Aorta

Front 31

Basic molecular unit of elastin? What is unique about it?

Back 31

Tropoelastin

less hydroxyproline than collagen

contains desmosine and isodesmosine (unique to elastin)

Front 32

If your body lacks copper, what portions of the ECM can't it produce?

Back 32

COLLAGEN or ELASTIN

Front 33

Orientation of oxytalan and elaunin?

Back 33

oxytalan- perpendicular

elaunin- parallel

Front 34

Defective fibrillin 2?

Back 34

congenital contractural arachnodactyly

Front 35

GAGs covalently bound to a core protein?

Back 35

proteoglycan

Front 36

Most ubiquitous protein-free GAG?

Back 36

Hyaluronic acid

Front 37

4 different types of GAGs that form proteoglycans?

Back 37

chondroitin sulfate

dermatan sulfate

keratan sulfate

heparan sulfate

Front 38

Versican is the most important proteoglycan, causes tautness of the skin, forms complex with hyaluronic acid. What is versican made of?

Back 38

Chondroitan and dermatan

Front 39

What is perlecan and where is it found?

Back 39

proteoglycan- found in BM

Front 40

Mutation in laminin 5? Antibodies to laminin 5?

Back 40

Laminin 5 aka Laminin 332

Mutation- dystrophic EB

Antibodies- antiepiligrin cicatricial pemphigoid

Front 41

Mutation of COL1?

Back 41

EDS Arthrochalasia --> hyperextensible skin, fragility, joint hypermobility (multiple joint dislocations), scoliosis

Front 42

Mutation of COL3?

Back 42

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

Front 43

Mutation of COL5?

Back 43

EDS Classic --> hyperextensible skin, fragility, joint hypermotility

Front 44

Mutation of Tenascin X?

Back 44

EDS Hypermobility --> joint hyperextensibility, otherwise benign

Front 45

Mutation of lysyl hydroxylase (PLOD1)?

Back 45

EDS Kyphoscoliosis --> kyphoscoliosis, muscle weakness, lung disease, joint laxity, ocular fragility

Front 46

Mutation of Dermatan -4- Sulfotransferase?

Back 46

EDS Musculocontractural --> craniofacial abnormalities, joint contractures, wrinkled palms

Front 47

Mutation of ADAMTS2?

Back 47

EDS Dermatosparaxis --> fragile saggins skin, easy bruising, hernias

Adam is a sprite

Front 48

Aside from the lax, redundant skin in cutis laxa, what are some of the other symptoms?

Back 48

pulmonary emphysema, pulmonary artery stenosis, bladder diverticula

Front 49

Mutation in ATP7A?

Back 49

Occipital Horn Syndrome

lax skin, tortuous arteries, joint hypermobility, occipital calcifications

Front 50

Defect in Marfans syndrome? Skin findings?

Back 50

Fibrillin 1

striae distensae, elastosis perforans serpiginosa, tall stature, pectus excavatum, high arched palate, aortic anuerysm, up/out dislocation of lens, spontaneous PTX

Front 51

Deficiency in homocysteinuria?

Back 51

CYSTATHIONINE BETA SYNTHEASE

Front 52

Yellow papules on the chest and neck, angiod streaks in eye, lax skin... mutation?

Back 52

Pseudoxanthoma elasticum

mutation of ABCC6

Front 53

Mutation in collagen 7? Autoantibodies to collagen 7?

Back 53

Mutation- dystrophic EB

Antibodies- EBA SLE

Front 54

Antibodies to ECM-1?

Back 54

lichen sclerosis

Front 55

Mutations of ECM-1?

Back 55

lipoid proteinosis

Front 56

Perforating disorders are broken into:

1.

2.

3.

Back 56

Perforating disorders are broken into:

1. acquired perforating dermatosis

2. elastosis perforans serpingosa

3. reactive perforating collagenosis

Front 57

Acquired perforating dermatosis are most common in what populations?

Back 57

10% prevalence in renal dialysis patients, can also see in DM, multiparous black women on belly

Kyrles disease

Front 58

Most effective therapy for acquired perforating dermatosis?

Back 58

UV light

Front 59

Reactive perforating collagenosis is most common in which populations?

Back 59

begins in childhood after superficial trauma --> patients develop keratotic papules that spontaneously resolve over 6-8 weeks

Front 60

With Verhoeff van Gieson stain, what color are collagen fibers?

Back 60

RED

Front 61

With Verhoeff van Gieson stain, what color are elastin fibers?

Back 61

BLACK

Front 62

Elastosis perforans serpiginosa is most commonly assoicated with what disorders?

Back 62

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

Front 63

What underlying disorder?

Back 63

Kyrle's disease, most common on legs

possible underlying renal disease, DM, multiparous black female

Front 64

The major component of the anchoring filaments is:

uncein

plectin

a6b4 integrin

laminin 5

collagen type IV

Back 64

laminin 5 aka epiligrin

Front 65

T/F

Elastic fibers are 90% elastin wrapped in fibrillin?

Back 65

TRUE- form 4% of the dry weight of the skin

Front 66

Desmosine and isodesmosine are typical AA found in:

collagen fibers

anchoring fibrils

elastic fibers

heparan sulfate

anchoring plaques

Back 66

elastic fibers

Front 67

Dystrophic EB results from a mutation in collagen type:

Back 67

VII

Front 68

What collagen is mutated in osteogenesis imperfecta?

Back 68

collagen 1

Front 69

Granulation tissue primarily contains:

collagen I

collagen II

collagen III

collagen IV

fibrin

Back 69

collagen III

it begins to form 4 days after injury

Front 70

The formation of granulation tissue depends of the presence of:

neuts

fibronectin

collagen I

platelets

collagen IV

Back 70

fibronectin- granulation tissue forms 4 days after injury

Front 71

homocystinuria has abnormal crosslinking of collagen because of a mutation in :

Back 71

cystathione synthase

Front 72

Type VII collagen is found in anchoring fibrils and in:

fetal skin

bone

amnion

aorta

BV

Back 72

amnion, ew

Front 73

Anchoring fibrils are primarily composed of? Mutation? Immuno?

Back 73

Collagen VII

Mutated- dystrophic EB

Immuno- EBA and BULLOUS SLE

Front 74

The main permeability barrier in the lamina densa is:

Back 74

heparan sulfate proteoglycan

Front 75

Retinoids upregulate transcription of which types of collagen?

Back 75

1 & 7

Front 76

Fragmentation and/or loss of elastic fibers is not seen in:

cutis laxa

marfans

anetoderma

pseudoxanthoma elasticum

buschke ollendorf syndrome

Back 76

buschke ollendorf syndrome

Front 77

What percent of the dry weight of skin is elastin?

Back 77

4%

Front 78

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

Back 78

elaunin fibers run parallel to the reticular dermis

Front 79

Most collagens in the skin are synthesized by:

Back 79

dermal fibroblasts

Front 80

Collagens 7 & 17 are synthesized by

Back 80

epidermal keratinocytes and fibroblasts

Front 81

Collagens 8 & 18 are synthesized by

Back 81

endothelial cells

Front 82

co factor required to hydroxylated proline?

Back 82

vitamin C

Front 83

co factor required to hydroxylate lysine?

Back 83

copper