Extracellular matrix

Question 1

Processes influenced by ECM

Answer 1

-Embryonogenesis
-Fibrosis
-Wound healing
-Cell behavior
-Carcinogenesis

Question 2

Marfan syndrome

Answer 2

Mutation in gene for fibrillin-1 which regulates formation of elastic fibers
Also get increased levels of TGF-beta

Question 3

Features of Marfan syndrome

Answer 3

Tall slender build, with long fingers and toes. Lens dislocation, and aortic weakening (think Abe Lincoln)

Question 4

Structural components of ECM

Answer 4

-Collagen
-Elastin

Question 5

Ehler-Danlos Syndrome

Answer 5

Inherited CT disorders with defective collagen synthesis
-Dermatosporaxis is a variant of this condition

Question 6

Absorptive components of ECM

Answer 6

-Glycoaminoglycans
-Proteoglycans

Question 7

Edema and proteoglycans

Answer 7

Edema is excessive accumulation of fluid in the ECM within body cavity
-Changes in concentration or properties of absorptive molecules in ECM can cause edema

Question 8

Adhesive components of ECM

Answer 8

-Fibronectin
-Laminin
-Others

Question 9

Fibronectin and wound healing

Answer 9

Fibronectin is critical for wound healing
-Binding sites for macrophages, endothelium, and fibroblasts
-Formation of granulation tissue matrix
-Influence cell function and protein expression

Question 10

Other roles of fibronectin

Answer 10

-Cell migration and differentiation during embryogenesis
-Hemostasis
-Carcinogenesis

Question 11

General patterns of injury to the ECM

Answer 11

-Increased destruction
-Decreased production
-Excessive production
-Deposition of abnormal substances

Question 12

What produces collagen

Answer 12

Fibroblasts

Question 13

What enzymes degrade collagen

Answer 13

MMP or collagenase

Question 14

Causes of increased destruction of ECM

Answer 14

-Excessive MMP activity
-Inflammation
-Immunologic reactions

Question 15

Morphology of increased destruction of ECM

Answer 15

-Corresponds to the different types of necrosis

Question 16

Histologic morphology of increased destruction of ECM

Answer 16

-Collagen swollen, uniformly eosinophilic, fragmented or absent
-Inflammation usually present

Question 17

Causes of decreased production of ECM

Answer 17

-Most are inherited diseases (collagen dysplasia)
-Nutritional deficiencies like Vitamin C

Question 18

Decreased production of ECM morphology

Answer 18

-Skin distensible and fragile
-Tears in skin

Question 19

Histologic morphology of decreased production of ECM

Answer 19

-No abnormalities in some cases
-Collagen of variable size and shape
-Abnormal organization

Question 20

Excessive production of ECM

Answer 20

-Associated with healing in irreversibly damaged tissue (fibrosis and scar formation)
-Excessive fibrosis can interfere with tissue and organ function

Question 21

Causes of excessive production ECM

Answer 21

-Upregulation of collagen-producing cells (mainly fibroblasts)
-Stimuli resulting in irreversibly damaged tissue (tissue replaced as part of healing)

Question 22

Morphology of Excessive production of ECM

Answer 22

-Dense, white, fibrous tissue replacing normal tissues and organs
-Abnormal relationships between tissues and organs

Question 23

Histologic morphology of excessive ECM

Answer 23

-Densely packed collagen
-Initially increased fibroblasts
-Later mostly collagen and few fibroblasts

Question 24

Common substances deposited in the ECM

Answer 24

-Amyloid
-Ca
-Fe
-Excessive collagen

Question 25

Amyloid

Answer 25

Beta pleated sheet protein. Can get deposited in ECM due to abnormal folding of amyloid proteins -Can't be degraded in ECM if misfolded

Question 26

Reasons for deposition of amyloid

Answer 26

-Normal proteins that misfold when produced in excess -Abnormal proteins formed due to mutation

Question 27

Morphology of amyloid deposition

Answer 27

Deposition either locally or systemically -Organs enlarged, firm and discolored -Detect with Lugol's iodine and sulfuric acid

Question 28

Histologic morphology of amyloid deposistion

Answer 28

-Eosinophilic, acellular, amorphous, fibrilllar extracellular protein displaces normal tissue -Stain with Congo red and turns apple green in polarized light

Question 29

Primary amyloidosis

Answer 29

-Associated with immunological dyshomeostasis and deposition of AL protein -Associated with plasma cell neoplasia that produce excessive immunoglobulin and immunoglobulin light chains

Question 30

Secondary amyloidosis

Answer 30

-Associted with chronic inflammation and tissue destruction with deposistion of AA protein -Cytokines and cell damage associated with chronic inflammation increase SAA and abnormal breakdown of these results in deposition of ECM

Question 31

Amyloidosis of aging

Answer 31

-AB amyloid occur in brain of older animals (alzheimers) -Less often occurs in heart, GI tract, and lungs of older dogs

Question 32

Endocrine amyloidosis

Answer 32

-Amyloid deposited in pancreas of cat in the islets -Common cause of type I diabetes mellitus

Question 33

Familial amyloidosis

Answer 33

Systemic deposition of AA occurs in some breeds and cats. SAA may be abnormal but usually still see chronic inflammatory component. Kidney and liver most commonly affected

Question 34

Deposition of calcium

Answer 34

Can occur in normal or abnormal situation

Question 35

Causes of Calcification

Answer 35

-Dystrophic -Metastatic

Question 36

Dystrophic calcification

Answer 36

-In necrotic tissue -Ca binds to damaged membrane phospholipids and starts crystal formation -Localized event

Question 37

Common locations of dystrophic calcification

Answer 37

-Heart -Skeletal muscle -Inflammatory lesions -Skins

Question 38

Metastatic calcification

Answer 38

In normal tissue -Reflection of usually hypercalcemia -Ca initiated by local alkalinity and alteration in collagen structure -Systemic

Question 39

Situation of metastatic calcification

Answer 39

-Renal failure (excess PTH, Dont see hypercalcemia) -Vitamin D toxicity -Pseudohyperparathyroidism -Neoplastic bone destruction

Question 40

Morphology of calcification

Answer 40

-Gross: gritty and white depsosits -Histologic: Purple material either in normal structures or disrupting the normal morphology

Question 41

Epidermolysis bullosa

Answer 41

COnditions with skin fragility and blistering/ Abnormal collagen type VII, keratin, laminin, and integrens

Question 42

Osteogenesis imperfecta

Answer 42

Abnormal type I collagen

Question 43

Muscular dystrophies

Answer 43

Defects in laminin or type VI collagen and decreased dystrophin levels

Question 44

Osteoarthritis and IVDD

Answer 44

Degeneration of multiple matrix components

Question 45

Vascular diseases

Answer 45

-Atherosclerosis -Aneurysm