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Flashcards in MSK Mod 2 Deck (60):

Synovial Joint is composed of?

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


Joint Capsule outer layer

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


Joint Capsule inner Layer

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


Joint Space

1. enclosed by capsule and filled with synovial fluid


Thixotropic properties

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


Synovial Fluid is

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


Hyaline articular Cartilage

a. thin covering on the ends of most bones
b. reduces friction, absorb/disperse compressive forces



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


Extra-cellular matrix-- Non-fibrous component of matrix

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


Extra cellular matrix-- Fibrous component of matrix

(i) collagen fiber (10-30% of cartilage)
1. collagen fibers arranged to absorb mechanical stress


Cartilage – bone interface Zones 1-4

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


Matrix Turnover (homeostasis)

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


Enzymes, hormones, and mechanical stimuli for Matrix Turnover

(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


Healthy Cartilage

• 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


Blood and Nerve Supply to Cartilage

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


Pain associated with Articular Cartilage

• 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.


Healing associated with Articular Cartilage

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


Osteoarthritis (degenerative joint disease)

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


Primary defect of OA

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


Gross articular cartilage changes-- pathology of OA

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


Enzymatic Changes in Articular Cartilage-- pathology of OA

(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


Hormone and Cytokine Changes-- pathology of OA

• 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


Nitric oxide (NO) and apoptosis-- pathology of OA

(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)


Articular cartilage function in OA

• 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


Net Result of Articular Cartilage Function in OA (1)

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


4 Secondary gross pathological changes associated with OA

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


Etiology of OA

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


Exercise as a risk factor for OA (3)

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


Pain patterns of OA (5)

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


Referred pain for OA (2)

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


Joint deformation and loss of function for OA

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)


3 Surgeries for OA

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



(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


Cartilage “repair” strategies

• 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


Joint Replacement (2)

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


Infectious Joint Disease (2)

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


Non infectious Joint Disease (2)

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


Overview of Rheumatoid Arthritis

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


MC Joints involved with RA

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


Etiology of RA

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


General systemic manifestations of inflammation of RA

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


Local manifestations of inflammation of RA

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


B lymphocytes -- pathology of RA

• 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


CD4 T helper cells-- pathology of RA

• 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


Hand deformities in RA

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


Extra Articular Manifestations of RA-- Cardiac and Eyes

• 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


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

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


Extra Articular Manifestations of RA-- Vasculitis

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


Diagnostic Criteria for RA

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


Treatments for RA

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


Juvenile Rheumatoid Arthritis (JRA)

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


Differences between JRA and RA

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



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


Pathogenesis of GOUT

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


Clinical Manifestations of Gout

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


Predisposing conditions of GOUT

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)


Ankylosing spondylitis

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


Etiology of Ankylosing Spondylitis

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


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

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


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

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