Cartilage

Question 1

Subchondral bone

Answer 1

Bone underneath articular cartilage

Question 2

Articular catilage structure

Answer 2

hyaline
firm rubber consistency, highly resilient, good at withstanding compression and shear stress
Low coefficient of friction
Highly hydrated
Calcified cartilage at anchoring site, active cartilage toward articular surface

Question 3

Composition of articular cartilage

Answer 3

65-80% water
primary fiber -type II collagen
proteoglycans help maintain hydration & responsible for compressibility
Chondrocytes - maintain matrix of cartilage
Avascular, nourished by synovial fluid

Question 4

Collagen in articular cartilage

Answer 4

Arrangement is specific
Closer to subchondral bone: collagen is arranged at right angles to surface of bone
Closer to articular surface: collagen sweeps out to run parallel to articular surface

Question 5

Proteoglycans in articular cartilage

Answer 5

Sulfated glycosaminoglycans and non-sulfated glycosaminoglycans
Chondroitin sulfate = aggrecan
GAGs have a highly negative charge, can hold onto lots of water
- bind to core protein, which binds hyaluronic acid through HA-binding region
- Core protein stabilized to hyaluronic acid via a linker protein
- together form a large complex
- PG-HA complex intertwine with collagen

Question 6

Cartilage function

Answer 6

sliding at joints
shock absorption - intervertebral discs
flexible support - trachea, ribs, ear
bone growth - epiphyseal growth plates

Question 7

Hyaline cartilage

Answer 7

widely distributed - most widespread in the body
slippery
matrix filled with type II collagen
low metabolic rate, low regenerative potential
Filled with chondroblasts –> give rise to chondrocytes that become isolated form blood supply and produce matrix
Whole skeleton is hyaline cartilage in embryonic and fetal development

Question 8

Elastic cartilage

Answer 8

rare
found in epiglottis, Eustachian tube, ear, external auditory meatus
Bendable but returns to original structure
Elastic fibers found in matrix
Little degeneration

Question 9

Fibrocartilage

Answer 9

Mixture of cartilage + dense regular CT
found at: tendon insertion, menisci, intervertebral discs
great tensile strength
type I collagen predominates - lined up in parallel with pull/stress

Question 10

Perichondrium

Answer 10

fibrous CT sheath
vascular supply for avascular cartilage
Chondrogenic layer found on inner surface of perichondrium - important for growth and maintenance

• not found in articular cartilage and fibrocartilage

Question 11

Chondrocytes

Answer 11

cells found in lacunae of matrix
grouped into isogenous nests
Secretes protein and CH

Question 12

ECM

Answer 12

Collagen - main component

• gives tensile strength
• hyaline: type II, fibrocartilage: type I predominates
• Elastin - elastic cartilage
• PGs - sulfated and non-sulfated GAGs attach to proteins

Question 13

Articular cartilage lubrication

Answer 13

Synovial fluid - also provides nutrients for chondrocytes
Non-compressible fluid, prevents surfaces from touching
Main lubricating component: lubricin - Glycoprotein synthesized from synoviocytes and chondrocytes
High water content (~90%): squeezed out of cartilage during loading, reabsorbed during relaxation

Question 14

Articular cartilage healing

Answer 14

Avascular - healing difficult

May heal with fibrocartilage

Question 15

Fibroblast - ECM role

Answer 15

embedded within certain types of CT
produce collagen in large amounts
maintains structure of CT

Question 16

Chondrocyte - ECM role

Answer 16

embedded within matrix of cartilage

pump out collagen and proteoglycans

Question 17

Isogenous groups of chondrocytes

Answer 17

Groups of chondrocytes gathered together in cartilage

derived from the same mother cells

Question 18

Territorial matrix

Answer 18

basophilic area
lots of sulfated GAG’s - lots of available negative charges
Picks up mor ebasophilia
found immediately surrounding the isogenous groups

Question 19

Interterritorial matrix

Answer 19

More collagen fibers
More proteins - more eosinophilia
acidophilic area
found further away from isogenous groups

Question 20

Type I collagen location

Answer 20

skin, tendons, vasculature, bone

most abundant collagen

Question 21

Type II collagen location

Answer 21

hyaline cartilage

Question 22

Collagen structure

Answer 22

all are triple helices

Question 23

Changes in cartilage due to normal aging

Answer 23

Mild fibrillation
Mild dehydration
Collagen - loss of tensile strength
Proteoglycans - smaller PGs and less aggregates
Normal number of chondrocytes

Question 24

Changes in cartilage due to disease

Answer 24

Severe fragmentation of collagen
Severe dehydration of cartilage
Less PGs: cleavage at HA binding region
Increased chondrocyte mitosis - produces increased number of chondrocytes

Question 25

Embryology of synovial joint

Answer 25

Forms between weeks 6-9 of development Development occurs from proximal to distal, upper extremities ahead of lower extremities 1) Homogeneous interzone: interzone between bones - undifferentiated mesenchymal cells found between two developing bones --> develops into articular surfaces, menisci, cruciate ligaments, collateral ligaments, synovial membrane 2) 3-layer interzone - densely packed cells become articular surfaces - resorption of loosely packed undifferentiated cells between articular surfaces 3) joint separation and cavitation - opposing articular surfaces - clear region: space between articular surfaces develop

Question 26

Synovial joint structure

Answer 26

Synovial membrane lies completely within joitn cavity, except at articular cartilage Layers: 1) Inner: thin syncytium - type A cells: specialized to clear waste - type B cells: specialized to produce HA 2) Outer: rich supply of blood vessels, lymph and nerves

Question 27

Synovial fluid

Answer 27

clear, viscous fluid Dialyzed plasma with glycoproteins and hyaluronic acid Contains collagenases, prostaglandins, proteinases Nourishes and lubricates joint surfaces Low volumes ~5 cc

Question 28

Joint capsule

Answer 28

Fibrous tissue joins two bones together | Areas of capsule thicken to resist specific motions --> ligaments

Question 29

Osteoarthritis

Answer 29

wearing out of articular cartilage in diarthrodial joints occurs with aging most common cause of chronic arthritis occurs more in large weight-bearing joints also see it in the hands (DIPs, PIPs)

Question 30

Changes seen in osteoarthritis (gross)

Answer 30

Appearance of osteophytes subchondral bone sclerosis Loss of metachromatic staining

Question 31

OA pathophys

Answer 31

Starts with fibrillations in articular cartilage --> confluent Chondrocytes self-produce IL1 and express IL1 receptors Initial injury --> produce building blocks of cartilage and degrading enzymes Eventually, get more MMP production > building blocks IL1 receptor binding results in upregulation of production of MMPs

Question 32

MMPs

Answer 32

MMP 1 and 13 - collagenases MMP 3 - stromelysin (degrades proteoglycans) production upregulated by IL1 receptor binding and plasmin

Question 33

Epidemiology of OA

Answer 33

``` Age Women Obesity Trauma Genetic - particular in fingers Metabolic factors, race ```

Question 34

Changes in cartilage in OA

Answer 34

Severe progressive fibrillation Severe fragmentation of collagen due to upregulation of collagenases Initial swelling of cartilage due to collagen breakdown, followed by severe dehydration Decreased # of PGs, decreased PG aggregates due to cleavage of HABR, regression to fetal chondroitin sulfate Chondrocyte cloning in capsules, mitosis

Question 35

OA management, non-surgical

Answer 35

``` Exercise Weight reduction Physiotherapy Pharmacological - acetaminophen - NSAIDs + cryoprotectants, oral/topical - tramadol (weak opiate narcotic) ``` injection: cortisone - short term, helps with pain and function, some inhibition of MMP viscosupplemntation: HA, potentially chondroprotective

Question 36

OA management, surgical

Answer 36

Arthroscopy - diagnosis | Arthroplasty: used for end-stage OA, dictated by severityof pain

Question 37

NSAID MOA

Answer 37

inhibits COX - reduce PGE2

Question 38

NSAID indication

Answer 38

antipyretic - primarily ibuprofen | anti-inflammatory/analgesia - indomethacin - high anti-inflammatory properties

Question 39

NSAID SEs

Answer 39

renal: vasoconstriction of afferent arteriole, reduce glomerular blood flow even worse in combination with ACE inhibitors - reduces amount of angiotensin II, which constricts efferent arteriole to maintain filtration pressure NSAIDs in people with HTN or heart failure can lead to edema GI: decrease protective mucus in GI tract direct irritation of mucosa - take iwth food/misoprostol/PPI

Question 40

COX1 vs COX2

Answer 40

COX1: constitutive, expressed everywhere, role in protection and maintenance COX2: inducible, expressed predominantly in inflamed tissue, proinflammatory and mitogenic

Question 41

COX-2 selective inhibitors

Answer 41

cardiovascular side effects COX2: largely responsible for maintaining non-adherent platelets Pushes balance towards more adherent platelets - increasing thrombosis, increased risk of MI and stroke

Question 42

Acetylsalicylic acid

Answer 42

effective analgesic + anti-inflammatory, but not tolerated well by GI tract Antiplatelet: at low doses (80 mg), acetylates COX1 in platelets, causes irreversible inhibition of COX1 throughout life of pltaelets - platelets become more non-adherent throughout their lifetime Analgesic/anti-inflammatory effects: occurs at higher doses Antipyretics: contraindicated in children - Reye's syndrome