Cartilage Response To Injury Lecture Flashcards
What type of cartilage is articular cartilage and where is it located
Joint surfaces, hyaline cartilage
Articular cartilage composition
70-80% water
Chondrocytes
Hyaline cartilage ECM
Type 2 collagen
Alpha chains are wound together in a triple helix
Large fibrilar structures
Arrange into arcade structure
Different that collagen in other locations
Normal cartilage is
Smooth, gray-white, glistening
Purpose of articular cartilage
Low friction gliding surface
Transmits weight bearing forces to underlying bone
Can withstand high cyclic loads
Injury to articular cartilage can be due to 2 things
Abnormal loading
Biochemical damage
Abnormal loading
Cyclic trauma
Direct, single overload trauma
Biochemical damage of articular cartilage
Joint inflammation, no direct trauma
Canine hip dysplasia
Improper alignment of the femoral head within acetabulum, increasing laxity
3 mutations in hip dysplasia
Mutations in formation of glycoprotein, proteoglycans, and fibrilar structure
Canine hip dysplasia is abnormal mechanical stress and vulnerability of tissues. This damages the …..
Articular cartilage
Joint homeostasis involves 2 processes
Anabolic synthesis and catabolic degradation
Injury starts cascade of inflammation and an increase in
Catabolism, degradation
In injury, chondrocytes are activated by
Stress
These cells act as their own inflammatory mediators
Chondrocytes
Injury causes the release of ……
Cytokines
Cytokines and examples
Modulate synthesis of catabolic enzymes
IL-1 beta, TNF alpha
Catabolic enzymes
MMP, Aggrecanase, IL-1
Catabolic enzymes are released by chondrocytes. The enzymes that breakdown collagen are
MMP which degrades the ECM
Chondrocytes release catabolic enzymes. The enzymes that break down proteoglycan are
Aggrecanase
Catabolic enzyme functions for cartilage injury
Collagen breakdown, proteoglycan breakdown, degradation of ECM
Physical articular cartilage injury steps (5)
Abnormal stress to normal cartilage (trauma)
Direct damage to chondrocytes and collagen
Release of catabolic enzymes that degrade PG and collagen
Decreased synthesis of matrix (compaction)
Cartilage damage (degeneration and thinning)
Biochemical articular cartilage steps (4)
Inflammation of surrounding tissues from age or use
Release of catabolic enzymes that degrade PG and collagen
Decreased synthesis of matrix
Cartilage damage
Tissue repair involves 2 things
Replacement of damage cells and matrix
Regeneration
General phases of tissue healing
Inflammation
Repair
Remodel
Inflammation step of tissue healing
Type of response?
How long?
Infiltration of?
What repairs?
Vascular response
3-5 days
Cellular infiltration (debridement)
Scaffold for repair
Repair step of tissue healing
Infiltration of?
What type of response?
How long?
Infiltration of cells, particularly fibroblasts
Local cellular response
2 days - 2 weeks
Remodeling step of tissue healing
Removal of?
How long?
Removal of inferior tissue + replacement
2 weeks - 1 year +
How is the inflammatory phase a problem for cartilage injury response
Cartilage is avascular, so there is no blood supply
No scaffold repair and no cellular infiltration
How is repair phase limited in cartilage injury response
No he;p with matrix synthesis by cellular infiltration since it is avascular
Larger defects of cartilage are filled with
Fibrocartilage
Problems with large defects being filled with fibrocartilage in cartilage injury response
Fibrocartilage has less gag and mostly collagen 1 so it is biochemically inferior which reduces function
Exclusive cartilage injury response step by step: trauma
Local death of chondrocytes and matrix loss
Exclusive cartilage injury response step by step: inflammation
No vascular infiltration
No cellular infiltration
No fibroblasts response to help healing
Exclusive cartilage injury response step by step: local repair
Local chondrocytes fill defect
Increased mitotic activity
Increased production of collagen and PG
Exclusive cartilage injury response step by step: remodeling
Incomplete, lesion remains
Complete repair in cartilage is …
Rare
Intrinsic cartilage repair
No vascular ingrowth
Relies on chondrocytes
CARTILAGE ONLY
Matrix flow
Forms lips of cartilage from perimeter that migrate towards center of defect
Can only heal small defects
Surface chondrocytes are more fibroblast-like
Fibrocartilage is added to large defects
CARTILAGE ONLY
Extrinsic cartilage repair
Vascular ingrowth from surrounding tissue
Mesenchymal elements from subchondral bone
Helps form new connective tissues
Articular cartilage repair 3 steps
Intrinsic repair
Matrix flow
Extrinsic repair
2 main limitations of cartilage repair
Avascular
Inferior repair tissue
Osteoarthritis
Articular cartilage damage and degeneration
Effects entire joint
Can start with injury to any part of the joint
Cartilage is part of a joint and the joint is an …
Organ
Gross features of early cartilage degeneration
Thinning, surface dullness and roughness
Histological features of early cartilage degeneration
PG loss with matrix contraction and clefts
Chondrocyte necrosis and loss
Progressive cartilage degeneration histological features
Larger areas of Chondrocyte loss
Development of Chondrocyte clones, chondrones
Loss of type 2 collagen in superficial to mid layers (goes to mid to deep layers)
Advanced cartilage degeneration gross features
Severe thinning and score lines
Yellow discoloration
Erosion, ulcers, subchondral hemorrhage
Advanced cartilage degeneration histological features
Matrix fibrillation (fraying)
Development of vertical fissures
Erosions
Loss of hyaline articular cartilage
End stage cartilage degeneration histological and gross features
Ulcers and subchondral bone hemorrhage
