Extracellular matrix Flashcards
Processes influenced by ECM
-Embryonogenesis
-Fibrosis
-Wound healing
-Cell behavior
-Carcinogenesis
Marfan syndrome
Mutation in gene for fibrillin-1 which regulates formation of elastic fibers
Also get increased levels of TGF-beta
Features of Marfan syndrome
Tall slender build, with long fingers and toes. Lens dislocation, and aortic weakening (think Abe Lincoln)
Structural components of ECM
-Collagen
-Elastin
Ehler-Danlos Syndrome
Inherited CT disorders with defective collagen synthesis
-Dermatosporaxis is a variant of this condition
Absorptive components of ECM
-Glycoaminoglycans
-Proteoglycans
Edema and proteoglycans
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
Adhesive components of ECM
-Fibronectin
-Laminin
-Others
Fibronectin and wound healing
Fibronectin is critical for wound healing
-Binding sites for macrophages, endothelium, and fibroblasts
-Formation of granulation tissue matrix
-Influence cell function and protein expression
Other roles of fibronectin
-Cell migration and differentiation during embryogenesis
-Hemostasis
-Carcinogenesis
General patterns of injury to the ECM
-Increased destruction
-Decreased production
-Excessive production
-Deposition of abnormal substances
What produces collagen
Fibroblasts
What enzymes degrade collagen
MMP or collagenase
Causes of increased destruction of ECM
-Excessive MMP activity
-Inflammation
-Immunologic reactions
Morphology of increased destruction of ECM
-Corresponds to the different types of necrosis
Histologic morphology of increased destruction of ECM
-Collagen swollen, uniformly eosinophilic, fragmented or absent
-Inflammation usually present
Causes of decreased production of ECM
-Most are inherited diseases (collagen dysplasia)
-Nutritional deficiencies like Vitamin C
Decreased production of ECM morphology
-Skin distensible and fragile
-Tears in skin
Histologic morphology of decreased production of ECM
-No abnormalities in some cases
-Collagen of variable size and shape
-Abnormal organization
Excessive production of ECM
-Associated with healing in irreversibly damaged tissue (fibrosis and scar formation)
-Excessive fibrosis can interfere with tissue and organ function
Causes of excessive production ECM
-Upregulation of collagen-producing cells (mainly fibroblasts)
-Stimuli resulting in irreversibly damaged tissue (tissue replaced as part of healing)
Morphology of Excessive production of ECM
-Dense, white, fibrous tissue replacing normal tissues and organs
-Abnormal relationships between tissues and organs
Histologic morphology of excessive ECM
-Densely packed collagen
-Initially increased fibroblasts
-Later mostly collagen and few fibroblasts
Common substances deposited in the ECM
-Amyloid
-Ca
-Fe
-Excessive collagen
Amyloid
Beta pleated sheet protein. Can get deposited in ECM due to abnormal folding of amyloid proteins
-Can’t be degraded in ECM if misfolded
Reasons for deposition of amyloid
-Normal proteins that misfold when produced in excess
-Abnormal proteins formed due to mutation
Morphology of amyloid deposition
Deposition either locally or systemically
-Organs enlarged, firm and discolored
-Detect with Lugol’s iodine and sulfuric acid
Histologic morphology of amyloid deposistion
-Eosinophilic, acellular, amorphous, fibrilllar extracellular protein displaces normal tissue
-Stain with Congo red and turns apple green in polarized light
Primary amyloidosis
-Associated with immunological dyshomeostasis and deposition of AL protein
-Associated with plasma cell neoplasia that produce excessive immunoglobulin and immunoglobulin light chains
Secondary amyloidosis
-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
Amyloidosis of aging
-AB amyloid occur in brain of older animals (alzheimers)
-Less often occurs in heart, GI tract, and lungs of older dogs
Endocrine amyloidosis
-Amyloid deposited in pancreas of cat in the islets
-Common cause of type I diabetes mellitus
Familial amyloidosis
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
Deposition of calcium
Can occur in normal or abnormal situation
Causes of Calcification
-Dystrophic
-Metastatic
Dystrophic calcification
-In necrotic tissue
-Ca binds to damaged membrane phospholipids and starts crystal formation
-Localized event
Common locations of dystrophic calcification
-Heart
-Skeletal muscle
-Inflammatory lesions
-Skins
Metastatic calcification
In normal tissue
-Reflection of usually hypercalcemia
-Ca initiated by local alkalinity and alteration in collagen structure
-Systemic
Situation of metastatic calcification
-Renal failure (excess PTH, Dont see hypercalcemia)
-Vitamin D toxicity
-Pseudohyperparathyroidism
-Neoplastic bone destruction
Morphology of calcification
-Gross: gritty and white depsosits
-Histologic: Purple material either in normal structures or disrupting the normal morphology
Epidermolysis bullosa
COnditions with skin fragility and blistering/ Abnormal collagen type VII, keratin, laminin, and integrens
Osteogenesis imperfecta
Abnormal type I collagen
Muscular dystrophies
Defects in laminin or type VI collagen and decreased dystrophin levels
Osteoarthritis and IVDD
Degeneration of multiple matrix components
Vascular diseases
-Atherosclerosis
-Aneurysm
