Auer Ch 78 Joint Biology And Pathobiology

Front 1

Back 1

Front 2

Back 2

Front 3

Types of joints:

Back 3

Synarthroses are immovable joints, amphiarthroses are slightly movable joints, and diarthroses are movable joints.

Front 4

Components of Joints:

Back 4

synovial membrane and fluid, periarticular ligaments and joint capsule, subchondral bone, and articular cartilage.

Front 5

The synovial membrane layers:

Back 5

intimal, subimtimal

Front 6

Function of intimal layer:

Back 6

responsible for the content of the synovial fluid

Front 7

Composition of intimal layer:

Back 7

1 to 4 cell layers thick and does not have a basement membrane. The cells of the intimal layers are synoviocytes

Front 8

Functions of synoviocytes:

Back 8

phagocytosis and protein secretion

Front 9

types of synoviocytes:

Back 9

A, B, C

Front 10

function of type A synoviocytes:

Back 10

phagocytosis or pinocytosis

Front 11

function of type B synoviocytes:

Back 11

protein secretion

Front 12

function of type C synoviocytes:

Back 12

both phagocytosis and protein secretion

Front 13

Examples of intimal proteins:

Back 13

hyaluronan, collagen, lubricin, pro-matrix metalloproteinases, IL, and eicosanoids

Front 14

What is Steric exclusion?

Back 14

process of separation of molecules by size, preventing large molecules from reaching the synovial fluid, and regulating fluid composistion

Front 15

What molecules regulate steric exclusion?

Back 15

Hyaluronan and lubricin

Front 16

Composition of e subintimal layer:

Back 16

fibrous, areolar, and fatty tissue. It contains blood vessels and nerves.

Front 17

Function of the subintima:

Back 17

allows smaller components of plasma to diffuse through the membrane from the vascular supply. Small molecules such as glucose, O2, CO2, and proteins less than 10kDa are diffusible to the synovial fluid, but larger molecules are not

Front 18

Function of Periarticular ligaments and joint capsule:

Back 18

stability to the joint

Front 19

The function of the subchondral bone:

Back 19

provide and contour and stability for the articular cartilage

Front 20

How does subchondral bone differ from cortical bone?

Back 20

arrangement of the haversian systems. In normal diaphyseal cortical bone, haversian systems are arranged parallel to the long axis of the bone but in subchondral bone the haversian systems are arrange parallel to the surface of the joint

Front 21

What is the Nutrient supply to articular cartilage?

Back 21

synovial fluid nutritional solutes diffuse through the cartilage matrix to the chondrocytes

Front 22

Components of articular cartilage:

Back 22

Chondrocytes account for 1-12% of the cartilage volume, with the remaining volume from the extracellular matrix

Front 23

Composition of articular cartilage extracellular matrix:

Back 23

collagen, proteoglycans and water

Front 24

What portion of the ECM is water?

Back 24

70%

Front 25

Function of articular cartilage Collagen:

Back 25

provide framework in which all the other components of the articular cartilage are confined and counteracts tensile forces on the joint surface

Front 26

Layers of articular cartilage:

Back 26

superficial, intermediate, deep, calcified

Front 27

Appearance of chondrocytes in superficial layer:

Back 27

most aabundant, aligned parallel to long axis of joint surface

Front 28

Appearance and size of collagen in superficial layer:

Back 28

small diameter collagen fibrils are aligned parallel to the long axis of the joint surface

Front 29

What is the lamina splendens?

Back 29

acellular layer of collagen in the superficial layer

Front 30

Appearance of chondrocytes in intermediate layer:

Back 30

oval to rounded chondrocytes

Front 31

Appearance and size of collagen in intermediate layer:

Back 31

larger diameter collagen fibrils are arranged in a random pattern

Front 32

Appearance of chondrocytes in deep layer:

Back 32

largest size of chondrocytes

Front 33

Appearance and size of collagen in deep layer:

Back 33

largest diameter collagen fibrils which are oriented perpendicular to the long axis of the joint surface

Front 34

Whatis the e calcified zone?

Back 34

mineralized cells and matrix

Front 35

What is the tide mark?

Back 35

junction of non-calcified and calcified cartilage.

Front 36

Predominate type of collagen in articular cartilage?

Back 36

type 2 collagen

Front 37

How does type 2 collagen differs from type 1?

Back 37

number of hydroxylysine molecules and the amount of glycosylation. The triple helical structure of type 2 collagen is composed of 3 identical molecules

Front 38

Function of Type 9 collagen:

Back 38

provides a covalent interface between type 2 fibrils

Front 39

Function of Type 11 collagen:

Back 39

found within the type 2 helix as a core filament onto which the type 2 molecules are deposited

Front 40

Predominate proteoglycan in articular cartilage:

Back 40

aggrecan

Front 41

Function of aggrecan:

Back 41

provides resistance to compressive forces

Front 42

Composition of aggrecan:

Back 42

core protein backbone and glycosaminoglycans that radiate from the core protein backbone

Front 43

What are the main GAG that radiate form the core protein backbone of aggrecan?

Back 43

Chondroitin 4 sulfate, chondroitin 6 sulfate and keratin sulfate

Front 44

Function of GAGs in aggrecan:

Back 44

repel each other and attract water, which creates a positive pressure

Front 45

Domains of core protein of aggrecan:

Back 45

G1, G2, and G3

Front 46

What is the GI domain on the aggrecan core protein?

Back 46

where the core protein interacts with hyaluronan

Front 47

Compomposition of Hyaluronan:

Back 47

forms a backbone to which 100s of aggrecan monomers are arranged

Front 48

What is the G2 domain on the aggrean core protein?

Back 48

adjacent to a keratin sulfate rich region and the target of enzymes that breakdown aggrecan

Front 49

How do Chondrocytes respond to mechanical stress?

Back 49

Low levels of mechanical stress favor catabolic processes but at normal physiologic levels of activity, anabolic processes are favored, resulting in a balance of metabolism. In superphysiologic mechanical stress, the anabolic pathways are overwhelmed by catabolic processes

Front 50

What do Joint mechanics depend on?

Back 50

kinematics, kinetics, and joint lubrication

Front 51

What is Kinematics?

Back 51

study of the motion of the articulating surfaces in relation to each other.

Front 52

types of kinematic joint motions:

Back 52

translation, rolling, sliding

Front 53

what is Translational motion?

Back 53

movement without rotation, such as 2 surfaces moving past each other

Front 54

what is rolling motion?

Back 54

the center of rotation is the point of contact between 2 surfaces and the distance of the surface contact is the same for both surfaces

Front 55

what is sliding motion?

Back 55

the point of contact is not the center of rotation and the contact area between the 2 surfaces is not equal

Front 56

what is kinetics?

Back 56

relationship of the forces that are created during motion of the joint and the load created across the surface of the joint

Front 57

what does kinetics accounts for?

Back 57

muscular, body weight, and contact forces acting on the joint in any given load bearing situation

Front 58

function of boundary lubrication?

Back 58

prevents adhesion and abrasion of 2 surfaces and does not depend on the physical properties of the lubricant or the surfaces

Front 59

main boundary lubricants in the joint:

Back 59

Hyaluronan and lubricin

Front 60

What is created with Fluid-film mechanisms?

Back 60

a wedge of fluid between 2 surfaces to provide low friction environment at physiologic loads

Front 61

Possible models for fluid-film mechanisms:

Back 61

are squeeze film, hydrodynamic, and elastohydrosynamic

Front 62

What is Elastohydrodynamic fluid-film mechanics:

Back 62

lubrication of the cartilage occurs because aggrecan attracting water to the articular surface. When the joint is loaded, water is squeezed out from the articular surface and interposed between the 2 surfaces

Front 63

Why does Osteoarthropathy develop?

Back 63

alteration of articular cartilage metabolism and articular cartilage matrix depletion

Front 64

When does Alteration of articular cartilage metabolism occur?

Back 64

when catabolic metabolism predominates, leading to tissue failure

Front 65

How can catabolic pathwaysoverwhelm joint metabolism?

Back 65

by being exposed to abnormal mechanical loads or a metabolic tissue failure

Front 66

When do Abnormal mechanical loads occur?

Back 66

from instability that overwhelms the normal reparative processes

Front 67

What is involved in Matrix depletion?

Back 67

synovial membrane and joint capsule, chondrocytes, matrix metalloproteinases, and cytokines

Front 68

Histologic abnormalities seen in the synovial membrane during disease:

Back 68

edema, hyperplasia of the intimal layer, increased vascularity, inflammatory cell infiltration and subintimal fibrosis

Front 69

What does Articular cartilage degeneration results from?

Back 69

loss of aggrecan and type 2 collagen, increased water content, increased surface fibrillation

Front 70

Source of MMP?

Back 70

synoviocytes and chondrocytes

Front 71

Function of MMP?

Back 71

collectively can degrade all portions of articular cartilage

Front 72

MMPs involved in induction of OA:

Back 72

MMP-1, MMP-8, MMP-13, which are all collagenases, MMP-3 is a stromolysin, and MMP-2 and MMP-9 are gelatinases

Front 73

What breaks down aggrecan?

Back 73

A structural and functional relative of the MMPs are the ADAM enzymes which is “a disintegrin and a metalloproteinase”

Front 74

Function of MMP-1:

Back 74

breaksdown type 2 & 10 collagen by breaking the each of the chains in the triple helix at a specific AA sequence

Front 75

What upregulates MMP-13?

Back 75

IL-1

Front 76

Examples of catabolic cytokines:

Back 76

IL-1, TNFa

Front 77

Source of IL-1, TNFa:

Back 77

chondrocytes and synoviocytes

Front 78

Function of IL-1:

Back 78

upregulation of MMP-13, upregulates production of NO and PGE2, inhibits synthesis of aggrecan and type 2 collagen, and inhibits production of natural anti-arthritic molecules such as TIMP and IL-1Ra

Front 79

Function of NO:

Back 79

degrade hyaluronan and collagen

Front 80

Examples of cytokines that regulate pro-inflammatory cytokines:

Back 80

IL-4, IL-10, IL-13

Front 81

How do IL-4, IL-10, IL-13 regulate pro-inflammatory cytokines?

Back 81

promoting synthesis of TIMP and IL-1Ra and inhibit the synthesis of IL-1

Front 82

Function of TIMP (tissue inhibitor of metalloproteinases):

Back 82

inhibit MMPs by binding on a one-to-one basis, forming an inactive complex

Front 83

What TIMP are involved in inhibiting joint related MMPs?

Back 83

TIMP-1, -2, and -3

Front 84

Source of TIMPs:

Back 84

secreted by chondrocytes and synoviocytes

Front 85

major anabolic cytokines:

Back 85

IGF and TGF

Front 86

how do Sensory nerves produce pain from joint disease?

Back 86

by responding to mechanical stimuli or to chemical mediators

Front 87

examples of Chemical mediators:

Back 87

kinins or neuropeptides like substance P

Front 88

how do chemical mediators produce pain from joint disease?

Back 88

affect pain fibers directly

Front 89

what role do PGE2 and IL-1 have on joint pain?

Back 89

sensitize pain fibers to be more reactive after mechanical stimulation

Front 90

Why does joint fluid viscosity change?

Back 90

decrease in hyaluronan or depolymerization of hyaluronan

Front 91

What do Intrinsic repair mechanisms rely on?

Back 91

chondrocytes to divide and repair the tissue

Front 92

How are small articular cartilage defects repaired?

Back 92

Matrix flow involves chondrocytes and matrix filling a defect from the periphery of the defect toward the center

Front 93

What do extrinsic repair mechanisms rely on?

Back 93

cells and factors contributed from cells other than chondrocytes

Front 94

What is an example of extrinsic joint repair?

Back 94

Microfracture, Defects in the subchondral bone supply a source of MSC and progenitor cells to the defect

Front 95

How are defects larger than 5mm in the articular cartilage repaired?

Back 95

extrinsic repair mechanisms.

Front 96

What hinders Extrinsic repair mechanisms?

Back 96

depleted aggrecan and type 2 collagen and poor reformation of the calcified cartilage layer and subchondral bone

Front 97

Collagenase MMPs:

Back 97

interstitial collagenase (MMP-1), neutrophil collagenase (MMP-8), collagenase 3 (MMP-13)

Front 98

What TIMP inhibit MMP-1 (interstitial collagenase)?

Back 98

1>2

Front 99

Function of MMP-8 (neutrophil collagenase)?

Back 99

Degrade type 2 collagen, aggrecan, link protein

Front 100

What TIMP inhibit MMP-8 (neutrophil collagenase)?

Back 100

1,2

Front 101

Function of MMP-13 (collagenase 3):

Back 101

degrade collagen type 2, 4, 9, 10, aggrecan, fibronectin

Front 102

What TIMP inhibit MMP-13?

Back 102

3

Front 103

Examples of stromolysin MMPs:

Back 103

MMP-3 (stromolysin-1) , MMP-10 (stromolysin-2)

Front 104

Function of MMP-3 (stromolysin-1):

Back 104

degrade aggrecan, fibronectin, denature collagen type 2

Front 105

What TIMP inhibit MMP-3:

Back 105

1>2

Front 106

Function of MMP-10 (stromolysin-2):

Back 106

degrade collagen type 4, 9, 10, 11, procollagen, link protein, decorin, elastin, laminin

Front 107

What TIMP inhibits MMP-10?

Back 107

3

Front 108

Examples of gelatinase MMP:

Back 108

MMP-2, MMP-9

Front 109

Function of MMP-2:

Back 109

denature collagen type 2, 10, 11, elastin

Front 110

What TIMP inhibits MMP-2?

Back 110

2>1

Front 111

Function of MMP-9:

Back 111

degrade aggrecan, fibroconectin, collagen type 9 & 11, proollagen, link protein, decorin, elastin

Front 112

what is the pathogenic mechanism of perarticular osteophytosis?

Back 112

Enchochondral ossification occurring at bony margin of unknown cause, possible repair attempt

Front 113

what is the pathogenic mechanism of asymmetric joint space thinning?

Back 113

Cartilage degeneration and loss usually at areas of weight bearing or high stress

Front 114

what is the pathogenic mechanism of subchondral sclerosis?

Back 114

Deposition of new bone as a response to change in force transmission and from healing of trabecular microfractures, significant sclerosis corresponds to full thickness cartilage loss

Front 115

what is the pathogenic mechanism of subchondral lysis?

Back 115

Possibly pressure necrosis from synovial fluid gaining access to subchondral plate via fissues or pressure necrosis from trauma

Front 116

what is the pathogenic mechanism of osteochondral bodies?

Back 116

Disintegration of joint surfaces or fractured osteophytes

Front 117

what is the pathogenic mechanism of advanced remodeling/ anylosis?

Back 117

Articular response to advance degeneration, environment more consistent with a fracture than a synovial joint