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ECC > Joint physiology (McCarrel) > Flashcards

Joint physiology (McCarrel) Flashcards

1
Q

Joint function

Anatomy

Physiology

A
  • Anatomy - mechanics
    • energy efficient motion
    • shock absorption
  • Physiology - biology
    • anabolism:catabolism
    • regulation of inflammation
    • response to dz/inflammation
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2
Q

Joint as a organ

A
  1. Articular (hyaline) cartilage
  2. Synovial membrane
  3. Synovial fluid
  4. Subchondral bone and epiphysis
  5. Ligaments, tendons, muscle
  6. Joint capsule
  7. Vascular supply
  8. Innervation
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3
Q

Anatomy and stability

A
  • Subchondral bone and epiphysis
    • shape of joint
      • shoulder vs tibiotarsal joint
        • shoulder - tons of muscle
        • tibiotarsal - not muscled
  • Joint capsule
    • range of motion
  • Periarticular and intra-articular ligaments
    • palmar medial intercarpal ligament
  • Tendons and muscle
    • suprascapular nerve injury-sweeny
    • suspensory ligament degeneration
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4
Q

Articular cartilage

A
  • Primary determinant of joint health
    • damage or loss is irreversible
    • no other substance can replace it
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5
Q

Articular cartilage

Components

A
  • Chondrocytes
  • ECM
    • collagen
    • proteoglycans
    • glycoproteins
    • mineral, lipids, etc
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6
Q

Chondrocytes

A
  • whithin lacunae in ECM
  • Isolated
  • Synthesize, organize, and regulate composition of ECM
  • Detect and respond to mechanical stimuli
  • little division
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7
Q

Type II collagen

A
  • Slow turnover
  • Framework for organization of ECM
  • Theory of arcade arrangement
  • Counteracts tensile stresses at joint surface
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8
Q

Proteoglycans

A
  • Aggrecan
    • major proteoglycan of ECM
    • aboubt 100 GAG/core protein
      • chondroitin suphate
      • karatan sulfate
    • about 100 core proteins bind to hyaluronan
    • GAGs - ve charge - attract water
    • resists compressive forces
  • Small proteoglycans
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9
Q

Nutrition of cartilage

A
  • No blood supply
  • Motion = nutrition
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10
Q

Synovial membrane

A
  • Subintimal layer
  • Intimal layer
    • Type A synoviocyte
      • phagocytes
    • Type B synoviocyte
      • protein secretion
        • synovial fluid components
        • inflammatory and catabolic cytokines
    • Type C synoviocyte
      • intermediary
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11
Q

Synovial fluid

A
  • Ultrafiltrate of plasma
    • low TP < 2g/dL
    • low cellularity
      • mononuclear cells predominate
  • Hyaluronan
    • large molecules
    • synovial fluid viscosity
    • high affinity for water
  • function
    • lubricate gliding surface
    • nutrition supply and waste removal from cartilage
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12
Q

Inflammatory cytokines and catabolic enzymes

A
  • Matrix metalloproteinases (MMP)
  • Aggrecanases
  • Cytokines
  • Prostaglandins
  • Oxygen derived free radicals
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13
Q

Matrix Metalloproteinases

A
  • Released from chondrocytes and synoviocytes in latent form
  • 25 different types
  • collagenases
    • MMP-1
    • MMP-8
    • MMP-13
  • ​Gelatinases: MMP-2, MMP-9
  • Stromelysin: MMP-3
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14
Q

Matrix metalloproteinases

Inhibitor

A
  • Tissue inhibitor of Metalloproteinases (TIMP)
    • binds 1:1 with MMP
      • => inactive complex
    • tetracycline family antibiotics
      • acts as anti MMPs
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15
Q

Aggrecanases

A
  • ADAMTS
    • a disintegrin and metalloproteinase with thrombospondin motifs
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16
Q

Inflammatory cytokines

IL-1 and TNF-alpha

A
  • IL-1 and TNF-alpha
    • inc product
      • MMPs
      • Oxygen free radicals
      • prostaglandins
    • inhibit collagen and aggrecan synthesis
    • upregulate each other
  • IL-1
    • inhibits production of
      • IMP
      • IL-1Ra: IL-1 receptor antagonist protein
17
Q

Inflammatory cytokines

inhibitors

A
  • Inhibitors
    • IL-1Ra binds IL-1 receptors
      • illicits no effect
    • Solubilized TNF-alpha receptors
      • not attached to cell wall
      • binding has no effect
18
Q

In order for TNF-alpha to have an effect…

A

It has to bind to its receptor in the cell membrane

19
Q

Prostaglandins

A
  • PGE2
    • ​upregulates pain response
  • Proteoglycan degradation
  • Sensitizes nerves to mediators of pain
  • Production stimulated by IL-1
20
Q

Oxygen Derived Free radicals

A
  • Produced by neutrophils and macrophages
  • Cleave proteoglycan, colagen and hyaluronan
  • ie: NO
21
Q

General sequence of events

Insult

A
  1. Trauma/inflammatory insult
    • => inflammatory/catabolic mediator production
    • +/- joint instability or incongruity
  2. Biochemical damage
    • Loss of proteoglycan precedes collagen degradation => progression
  3. Chondrocytes can’t adequately replace lost proteoglycans and collagen
  4. Biomechanically inferior cartilage further damaged by normal stresses
  5. Wear particles from damaged cartilage
    • => further catabolism and inflammation
22
Q

Cartilage healing

A
  • Chondrocytes
    • limited capacity for repair
  • 3 types of healing
    1. Intrinsic repair​
      • chondrocyte synthetic activity
    2. Extrinsic repair
      • cells from marrow cavity
        • requries penetration of subchondral bone
    3. Matrix flow
      • cartilage ‘melts’ to fill lesion
23
Q

Types of cartilage injury

A
  • Partial thickness
    • can only heal by: intrinsic, and matrix flow
  • Full thickness
    • will have all three types of repair
  • Osteochondral defect
    • into bone
    • cells from marrow cavity can migrate into and fill defect

ECC (18 decks)

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