MSK Mod 2

Question 1

Synovial Joint is composed of?

Answer 1

1. joint capsule
   a. fibrous joint capsule (articular capsule)
   b. synovial membrane (inner layer)
2. joint space (cavity)
3. synovial fluid
4. articular cartilage

Question 2

Joint Capsule outer layer

Answer 2

a. fibrous capsule or stratum fibrosum
• poor blood supply but rich in joint receptors (sensory receptors)
• CT of joint capsule

Question 3

Joint Capsule inner Layer

Answer 3

a.	synovium (or stratum synovium) functions:
•	synovial fluid production
•	immune function
•	secrete immunoglobulins 
•	secrete lysosomal enzymes 
•	secrete hyaluronate (hyaluronic acid)
(i)	glycoaminoglycan “gel” to improve viscosity of synovial fluid 
•	secrete lubricating glycoproteins 
•	reduce friction in joint
•	ingest debris

Question 4

Joint Space

Answer 4

1. enclosed by capsule and filled with synovial fluid

Question 5

Thixotropic properties

Answer 5

viscosity varies inversely with velocity of movement

a. Rest – synovial fluid resists movement of the joint
b. Movement – synovial fluid provides less resistance to movement

Question 6

Synovial Fluid is

Answer 6

1. Clear, viscous fluid
2. Provides lubrication for the joint surfaces to create “frictionless” surfaces between bones
3. Thixotropic properties

Question 7

Hyaline articular Cartilage

Answer 7

a. thin covering on the ends of most bones

b. reduces friction, absorb/disperse compressive forces

Question 8

Chondrocytes

Answer 8

(i) produce and maintain extra-cellular matrix
1. produce and secrete enzymes that assist in matrix (collagen, PGs) turnover
(ii) forms 2% of cartilage

Question 9

Extra-cellular matrix– Non-fibrous component of matrix

Answer 9

(i) proteins, proteoglycans’s, etc.. (5-10% of cartilage)
1. regulate fluid flow in/out cartilage
(ii) water (60-80% of cartilage

Question 10

Extra cellular matrix– Fibrous component of matrix

Answer 10

(i) collagen fiber (10-30% of cartilage)

1. collagen fibers arranged to absorb mechanical stress

Question 11

Cartilage – bone interface Zones 1-4

Answer 11

i. Zone 1 – smooth surface, reduce friction of joint surface
ii. Zone 2 & 3 – transitional zones, absorb compressive forces
iii. Tidemark – interface between uncalcified and calcified layers
iv. Zone 4 – calcified cartilage, anchors cartilage to bone

Question 12

Matrix Turnover (homeostasis)

Answer 12

• Optimal joint function requires consistent matrix turnover
• Enzymes, hormones, and mechanical stimuli all play role in maintaining matrix turnover

Question 13

Enzymes, hormones, and mechanical stimuli for Matrix Turnover

Answer 13

(i) Enzymes:
1. Chondrocytes – secrete enzymes to assist in breakdown and rebuilding of matrix
(ii) Hormones:
1. GH (growth hormone) and IGF (insulin growth like factor) stimulate chondrocytes and play role in regulating matrix turnover
(iii) Mechanical load:
1. normal wt bearing forces required to stimulate optimal matrix turnover

Question 14

Healthy Cartilage

Answer 14

• Wt bearing activity will “push” fluid (water/synovial fluid) out of cartilage
• Fluid flow becomes slower and resistance becomes exponentially harder the more the cartilage is compressed
(i) Proteoglycans are responsible for regulating fluid flow in/out of cartilage
• Release of wt bearing force allows fluid to re-enter back into cartilage
• Net result:
(i) this cycle protects against compressive forces and allows for nutrients to pass in/out of cartilage to reach chondrocytes

Question 15

Blood and Nerve Supply to Cartilage

Answer 15

a. Articular cartilage does not have any nerve or blood supply

Question 16

Pain associated with Articular Cartilage

Answer 16

• Pain insensitive

(i) Pain associated with joint injuries/pathology IS NOT from the articular cartilage
(ii) Pain results from inflammation/swelling/irritation of pain sensitive tissues such as joint capsule/synovium, periosteum, increased subchondral bone pressures, tendon/ligament insertion sites and protective muscle spasm.

Question 17

Healing associated with Articular Cartilage

Answer 17

• Poor healing

(i) Articular cartilage has poor ability to regenerate after injury because of poor blood supply

Question 18

Osteoarthritis (degenerative joint disease)

Answer 18

A. Classified as “non-inflammatory” joint disease however evidence exists that there is an inflammatory component in OA
B. MC joint disease

Question 19

Primary defect of OA

Answer 19

loss/disruption of articular cartilage
a. Multiple factors contribute to cascade of events leading to OA
• Matrix destruction involving chondrocytes, collagen and proteoglycans

Question 20

Gross articular cartilage changes– pathology of OA

Answer 20

• smooth glossy surface becomes a dull yellow/brown gray color with surface flaking fissures and fibrillation

Question 21

Enzymatic Changes in Articular Cartilage– pathology of OA

Answer 21

(i) excessive enzyme secretion from chondrocytes leads to matrix breakdown
1. proteoglycans, collagen and glycoaminoglycans broken down by lytic enzymes
2. loss of proteoglycans in cartilage disrupts fluid regulation
a. water flows in/out of cell “too easily”
3. elevated PGs found in synovial fluid
(ii) enzymes produced from synovium also contribute to matrix (collagen) breakdown

Question 22

Hormone and Cytokine Changes– pathology of OA

Answer 22

• Hormones:
(i) chondrocytes becomes less sensitive to GH/IGF

• Cytokines:

(i) excessive production of IL-1 from synovium and chondrocytes leads to inhibition of normal cytokine regulation of matrix turnover
(ii) IL-1 facilitates NO synthesis
(iii) IL-1 is an inflammatory cytokine

Question 23

Nitric oxide (NO) and apoptosis– pathology of OA

Answer 23

(i) NO not normally found in healthy joint but is found in synovial fluid and synovium of patients with OA
(ii) NO facilitates chondrocyte death (apoptosis)
1. cartilage calcification also facilitates chondrocyte death (apoptosis)

Question 24

Articular cartilage function in OA

Answer 24

• Disruption of cartilage matrix allows fluid to flow in/out easier
• Fluid changes occur:
(i) Rest (non-weight bearing):
1. increased volume of water within cartilage
(ii) Wt bearing activity:
1. the fluid is pushed out of cartilage rapidly and cartilage is easily compressed without much resistance
2. “Release” of wt bearing allows increased volume of fluid to re-enter cartilage

Question 25

Net Result of Articular Cartilage Function in OA (1)

Answer 25

(i) Cartilage has limited ability to absorb forces and provide adequate “nutrients” to chondrocytes

Question 26

4 Secondary gross pathological changes associated with OA

Answer 26

a. OA effects surrounding structures and not just the articular cartilage b. subchondral bone sclerosis and bone cysts • may be asymptomatic unless severe • potential to communicate with the fissures and release contents into synovial fluid of joint space c. osteophyte formation • may led to irritation of synovium • may contribute to loss of gross movement d. synovial thickening • may contribute to loss of gross movement

Question 27

Etiology of OA

Answer 27

``` a. Trauma and genetics appear to account for a largest risk • trauma…acute or chronic damage (i) direct damage to joint (ii) inflammatory response in healing b. joint/ligament laxity c. inflammatory conditions d. neurological disorders…loss of normal sensory pathways • lead to abnormal movement…damage joint ```

Question 28

Exercise as a risk factor for OA (3)

Answer 28

a. Running, walking, etc…have low or no additional risk b. High impact sports tend to increase risk due to traumatic type forces or injuries • Shearing twisting high impact movements increase stress

Question 29

Pain patterns of OA (5)

Answer 29

a. morning pain b. pain following prolonged postural positions c. relief of pain with “easy” activity…increased pain with “extreme” activity d. pain in extreme wt bearing movements (kneeling, squatting, stairs, sports, etc…) e. may experience “good day/bad day” pattern but overall experience chronic episodes

Question 30

Referred pain for OA (2)

Answer 30

a. spine: potential for nerve root entrapment | b. LE joints: hip may refer to knee, hip to ankle, knee to hip, etc

Question 31

Joint deformation and loss of function for OA

Answer 31

3. joint deformation a. joint capsule thickening 4. loss of function/mobility a. limited ROM due to decreased congruency, osteophytes or secondary to pain b. gradual loss in weight bearing ability if lower extremity (hip, knee)

Question 32

3 Surgeries for OA

Answer 32

a. Viscosupplementation b. Cartilage “repair” strategies c. Joint replacement (arthroplasty)

Question 33

Viscosupplementation

Answer 33

(hyaluronan injections - joint fluid therapy) • inject of gel-like substances (hyaluronates) into the joint space to improve the viscous properties of synovial fluid • FDA approved for knee only

Question 34

Cartilage “repair” strategies

Answer 34

• Arthroscopic lavage and debridement (i) Technically not a cartilage “repair” • Marrow stimulating techniques (microfracture) • Osteochondral autografts and allografts • Cell-based repairs including autologous chondrocyte implantation

Question 35

Joint Replacement (2)

Answer 35

* Last resort if all other strategies failed or not appropriate * Criteria: elective procedure determined by pain and quality of life

Question 36

Infectious Joint Disease (2)

Answer 36

1. inflammation directly d/t bacteria, virus, fungi, protozoa, etc… 2. Example: Lyme disease, Rocky Mountain spotted fever

Question 37

Non infectious Joint Disease (2)

Answer 37

1. inflammation d/t autoimmune reactions | 2. Examples: RA, JRA, gout, ankylsosing spondylitis

Question 38

Overview of Rheumatoid Arthritis

Answer 38

1. systemic autoimmune disorder that causes chronic inflammation of connective tissue primarily in joints a. primary tissue involved: • synovial membrane is initial and primary tissue involved b. secondary tissues involved: • chronic inflammation gradually destroys articular cartilage, fibrous joint capsule, menisci, surrounding ligaments/tissue, bone

Question 39

MC Joints involved with RA

Answer 39

a. Fingers, wrist, elbow b. Knee, ankle, foot c. most often presents with involvement in the feet and hands • MP joints, PIP joints, and wrists are first to become symptomatic

Question 40

Etiology of RA

Answer 40

1. cause of RA not clear a. most autoimmune diseases often thought to be d/t… • abnormal immune response to a virus or infection • as body attack’s initial virus/infection it is “tricked” into programming it’s immune system to attack it’s own tissue (i) exposure to antigens → body makes “new” antibody that attacks it’s own tissue 2. RF (rheumatoid factor) = “new” antibodies a. classes of antibodies in RF…(IgM, IgG and occasionally IgA) present in RA

Question 41

General systemic manifestations of inflammation of RA

Answer 41

a. fever, fatigue, weakness, anorexia, wt loss, general achiness/stiffness b. symmetrical polyarthralgias

Question 42

Local manifestations of inflammation of RA

Answer 42

a. joint is painful, tender and stiff b. morning stiffness (“first hour”…obviously will vary) • d/t swelling in and around joint c. progressive joint limitation d/t pain and gradual destruction d. palpation…joint feels warm

Question 43

B lymphocytes -- pathology of RA

Answer 43

* facilitate formation RF (rheumatoid factor) * RF facilitates formation of autoimmune complexes that are deposited in joint tissue * Macrophages/phagocytes consume autoimmune complexes and also release lytic enzymes that destroy synovium

Question 44

CD4 T helper cells-- pathology of RA

Answer 44

* Facilitate release of inflammatory enzymes that have destructive effect on joint structures (synovium, articular cartilage, joint capsule, tendon/ligaments) * Facilitate release of RANKL which promotes osteoclast activity creating erosive lesions in bone surrounding the joint

Question 45

Hand deformities in RA

Answer 45

a. “Z deformity” = radial deviation of the wrist + ulnar deviation of fingers b. swan-neck = extend PIP and flex DIP c. boutonniere deformities = flex PIP and extend DIP

Question 46

Extra Articular Manifestations of RA-- Cardiac and Eyes

Answer 46

• cardiac (i) pericarditis, cardiomyopathy, and valvular incompetence caused by nodules, and interstitial fibrosis • eyes (i) scleritis (ii) rheumatoid scleritis is the most common ocular complication of RA, and suggests poor prognosis a. patients with extra-articular manifestations have increased mortality rate as well as more severe disability b. extra-articular manifestations are more common w/ high-titer RF

Question 47

Extra Articular Manifestations of RA-- Nervous System, Kidneys, Hematopoietic system

Answer 47

d. nervous system • neuropathies (peripheral nerve compression) – median nerve ,etc… e. kidneys • amyloid deposition f. hematopoietic system (Felty's syndrome): • anemia, splenomegaly, and leukopenia

Question 48

Extra Articular Manifestations of RA-- Vasculitis

Answer 48

* d/t elevated levels of circulating immune complexes (IgG etc…) * usually is a non-necrotising arteritis of the small terminal arterials,

Question 49

Diagnostic Criteria for RA

Answer 49

1. Diagnosis of RA is made in presence of 4 or more of the following and if joint s/s are present for 6 + weeks a. morning stiffness > 1 hour b. arthritis of 3+ joints c. arthritis of hands d. symmetrical involvement e. rheumatoid nodules over extensor surfaces or bony prominences f. elevated RF (serum rheumatoid factor) present

Question 50

Treatments for RA

Answer 50

1. Activity modifications a. Limit exercise during periods of exacerbation 2. Medical a. Medications to reduce inflammation, inhibit immune responses and rheumatic disease modifying drugs b. Surgical • Correct deformity • Correct mechanical imbalances…hand surgery

Question 51

Juvenile Rheumatoid Arthritis (JRA)

Answer 51

1. approximately 5% cases of adult RA begin in childhood 2. F>M 3. basic pathology the is the same as adult RA a. synovial proliferation/inflammation leads to joint destruction • severe joint destruction is seen in only 5% of patients

Question 52

Differences between JRA and RA

Answer 52

a. antinuclear antibodies (ANA) in serum while RF not usually found b. large joints effected in JRA c. more often involves cervical spine • subluxation of C1-2 in spine d. arthritis is generally less destructive e. fever, rash, leucocytosis, and lymphadenopathy with splenomegaly are common features

Question 53

GOUT

Answer 53

1. gout is a result of hyperurcemia (excess uric acid in blood) that causes joint destruction, soft tissue deposits and kidney damage 2. M.F (7:1 to 9:1) 3. age: onset of attacks usually begin in ages of 30 - 50

Question 54

Pathogenesis of GOUT

Answer 54

1. uric acid is end product of purine metabolism a. excess synthesis or a reduced elimination of uric acid results in hyperurcemia 2. hyperurcemia deposits in connective tissues surrounding joint (bursae, ligaments, articular cartilage, and synovial membranes) 3. uric acid saturates the synovial fluid and crystallizes 4. urate crystals in the joint provoke inflammatory response 5. over time joint destruction occurs 6. chronic elevation of uric acid forms subcutaneous deposits known as tophus

Question 55

Clinical Manifestations of Gout

Answer 55

1. hyperurcemia a. patient is asymptomatic 2. acute and recurrent attacks of monoarticular arthritis a. 90% of cases the first attack is the MTP (metatarsal-phalageal) joint of the first toe (“big toe”) b. joint is swollen and warm c. decreased weight bearing due to pain d. systemic effects…fever, tachycardia, fatigue e. attacks last 2 – 3 days • spontaneous remission • reoccurrence may occur as soon as few weeks but usually longer (i) after 1st attack, 2/3 of these pts will develop 2nd attack w/in 1 year; (ii) w/in 2 years, three fourths will suffer a second attack; • gradually attacks are closer together as disease progresses 3. Tophi deposits in subcutaneous regions a. ears, elbow, patella b. usually not painful 4. renal disease a. kidney tissue damaged by deposits of uric acid 5. formation of renal stones a. elevated levels of uric acid in the urine increase the chance they will crystallize to form kidney stone

Question 56

Predisposing conditions of GOUT

Answer 56

1. common chronic diseases assoc w/gout include alcoholism, obesity, hypertension, CAD, and hypertriglyceridemia; 2. increased dietary purine intake; 3. decreased puring biosynthesis (lack of serum enzyme uricase) 4. prolonged use of diuretics (thiazide diuretics may precipitate gout)

Question 57

Ankylosing spondylitis

Answer 57

A. Chronic inflammatory joint disease resulting in stiffening and fusion of the spine and SI joint

Question 58

Etiology of Ankylosing Spondylitis

Answer 58

1. autoimmune but process unclear | 2. associated with HLA-B27 (human leukocyte antigen)

Question 59

Immune/inflammation response attack fibrocartilage structures of the joints for Ankylosing Spondylitis

Answer 59

a. joint capsule b. intervertebral discs c. entheses (attachment sites of tendon, ligament and joint capsule) d. periosteum

Question 60

Inflammation damages these structures causing reparative reaction from fibroblasts for Ankylosing Spondylitis

Answer 60

a. Fibroblasts secrete collagen forming “scar tissue” b. Scar tissue eventually becomes calcified and ossified resulting in fusion of spinal joints and obliteration of SI joint