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3 > Cartilage > Flashcards

Cartilage Flashcards

1
Q

Subchondral bone

A

Bone underneath articular cartilage

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2
Q

Articular catilage structure

A

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

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3
Q

Composition of articular cartilage

A

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

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4
Q

Collagen in articular cartilage

A

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

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5
Q

Proteoglycans in articular cartilage

A

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

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6
Q

Cartilage function

A

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

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7
Q

Hyaline cartilage

A

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

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8
Q

Elastic cartilage

A

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

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9
Q

Fibrocartilage

A

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

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10
Q

Perichondrium

A

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
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11
Q

Chondrocytes

A

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

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12
Q

ECM

A

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
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13
Q

Articular cartilage lubrication

A

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

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14
Q

Articular cartilage healing

A

Avascular - healing difficult

May heal with fibrocartilage

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15
Q

Fibroblast - ECM role

A

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

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16
Q

Chondrocyte - ECM role

A

embedded within matrix of cartilage

pump out collagen and proteoglycans

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17
Q

Isogenous groups of chondrocytes

A

Groups of chondrocytes gathered together in cartilage

derived from the same mother cells

18
Q

Territorial matrix

A

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

19
Q

Interterritorial matrix

A

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

20
Q

Type I collagen location

A

skin, tendons, vasculature, bone

most abundant collagen

21
Q

Type II collagen location

A

hyaline cartilage

22
Q

Collagen structure

A

all are triple helices

23
Q

Changes in cartilage due to normal aging

A 
Mild fibrillation
Mild dehydration
Collagen - loss of tensile strength
Proteoglycans - smaller PGs and less aggregates
Normal number of chondrocytes
24
Q

Changes in cartilage due to disease

A

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

25
Q

Embryology of synovial joint

A

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

26
Q

Synovial joint structure

A

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

27
Q

Synovial fluid

A

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

28
Q

Joint capsule

A

Fibrous tissue joins two bones together

Areas of capsule thicken to resist specific motions –> ligaments

29
Q

Osteoarthritis

A

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)

30
Q

Changes seen in osteoarthritis (gross)

A

Appearance of osteophytes
subchondral bone sclerosis
Loss of metachromatic staining

31
Q

OA pathophys

A

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

32
Q

MMPs

A

MMP 1 and 13 - collagenases
MMP 3 - stromelysin (degrades proteoglycans)

production upregulated by IL1 receptor binding and plasmin

33
Q

Epidemiology of OA

A 
Age
Women
Obesity
Trauma
Genetic - particular in fingers
Metabolic factors, race
34
Q

Changes in cartilage in OA

A

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

35
Q

OA management, non-surgical

A 
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

36
Q

OA management, surgical

A

Arthroscopy - diagnosis

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

37
Q

NSAID MOA

A

inhibits COX - reduce PGE2

38
Q

NSAID indication

A

antipyretic - primarily ibuprofen

anti-inflammatory/analgesia - indomethacin - high anti-inflammatory properties

39
Q

NSAID SEs

A

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

40
Q

COX1 vs COX2

A

COX1: constitutive, expressed everywhere, role in protection and maintenance

COX2: inducible, expressed predominantly in inflamed tissue, proinflammatory and mitogenic

41
Q

COX-2 selective inhibitors

A

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

42
Q

Acetylsalicylic acid

A

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

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