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Fall 2014 > KIN 429 Midterm 2 > Flashcards

KIN 429 Midterm 2 Flashcards

1
Q

Mechanism and outcomes of nitrogen containing bisphoshphonates

A

Inhibit pyrophosphate synthase which in involved in intracellular signaling. Leads to osteoclast inactivation and decreased bone turnover

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2
Q

Mechanism and outcomes of Denosumab

A

RANKL inhibitor; inhibits OC formation, function and survival

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3
Q

Mechanism and outcomes of selective estrogen receptor modulators

A

Binds to estrogen receptors with the same affinity as estradiol; estrogen agonists in some tissue (bone and lipids) and antogonistic in others (uterus and breast); leads to increased osteoblast and osteocyte survival and osteoclast apoptosis

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4
Q

Mechanism and outcomes of teriparatide

A

Fragment of PTH molecule, so it acts like PTH. Continuous exposure to elevated PTH enhances osteoclast formation and bone loss, intermittent exposure to PTH will activate osteoblasts more than osteoclasts

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5
Q

Mechanism and outcomes of hormone replacement therapy

A

Replacing estrogen, however, WHI suggested that risk outweighs benefits

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6
Q

Names of nitrogen containing bisphosphonates

A

Fosamax, Actonel, Aclasta

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7
Q

Names of Denosumab drug

A

Prolia

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8
Q

Type of drug Evista is

A

Selective estrogen receptor modulator

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9
Q

Name of teriparatide drug

A

Forteo

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10
Q

Relation of PTHrP in cancer and bone health

A

Tumor produces PTHrP, leading to increased osteoclastic bone resoprtion, increased renal tubular resorption of calcium

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11
Q

What ways does cancer treatment increase bone loss?

A

Aromatase inhibitors and other drugs; ovarian function (surgery, radiation, drugs), chemotherapy (toxic effect on osteoblasts, can affect gonadal steroid production)

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12
Q

Symbiotic relationship between tumor growth and bone breakdown

A

Tumor secretes PTHrP, which increases RANKL, which activates osteoclasts, which secrete transforming growth factor beata, which stimulates tumor growth

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13
Q

Some cancers related to bone

A

osteosarcoma, chondrosarcoma, Ewing sarcoma, giant cell myeloma, chordoma, fibrosarcoma, lymphoma, multiple myelmoa, bone metastases

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14
Q

What is multiple myeloma?

A

A cancer of the plasma cells which reside in the bone marrow and can cause bone lesions and kidney dysfunction

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15
Q

What is metastasis?

A

A process where tumor cells spread to other places in the body, transported by the lymphatic circulation or in the blood, implanted away from original site of tumor in other places/organs

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16
Q

8-% of bone metastases occur from what 3 cancers?

A

prostate, breast, and lung

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17
Q

Osteolytic bone metastases

A

Increased bone resorption with little bone formation; most common in lung, renal, and breast cancer patients; skeletal destruction mediated by osteoclasts rather than tumor cells

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18
Q

Osteoblastic bone metastases

A

Increased bone formation, but poor quality. Most commonly seen in prostate cancer patients. Prostate tumor cells produce factors that stimulate osteoblast activity to produce abnormal bone; may be release of growth factors that may further stimulate tumor cell growth

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19
Q

Consequences of bone metastases in cancer

A

pain, hypercalemia (increased bone resoprtion), fractures, cancer not curable, longer time living with cancer –> skeletal manifestations influence quality of life

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20
Q

Cancer therapeutic strategies to treat bone metastases

A

radiation therapy, bisphosphonates, denosumab

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21
Q

Potential adverse adverse effects of bisphosphonates

A

Osteonecrosis of the jaw

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22
Q

Exercise considerations for indivduals with cancer

A

fall risk (neuropathy), fracture risk (secondary bone loss, metastases, post-menopausal), fatigue, immune suppression, pain, weakness

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23
Q

Denosumab for bone metastases in cancer

A

Delays time to developing first skeletal-related event, and reduces risk of multiple events in those with malignancies involving bone. Comparable efficacy to bisphosphonates. Inhibits RANKL binding to RANK

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24
Q

Bisphosphonates for bone metastases in cancer

A

Effective in controlling bone pain, hypercalemia and preventing skeletal-related events by 50%. Osteolytics lesions do not heal with bisphosphonates treatment. Osteonecorsis of the jaw a potential adverse effect.

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25
Q

Synarthroses?

A

Fixed joints; adjoining cranial plates separated by fibrous tissue, provide for growth

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26
Q

Amphiarthroses?

A

Bones bound by flexible fibrocartilage, permits modest motion (pubic symphysis and intervertebral discs)

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27
Q

Diarthroses?

A

synocvial joints, moveable joints, surrounded by synovial membrane and fluid

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28
Q

Classifications of joints according to shape

A

ball and socket (hip and shoulder), hinge (interphalangeal, knee), saddle (first carpometacarpal), plane (patellofemoral), pivot (proximal and distal radioulnar joints)

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29
Q

Components of a synovial joint

A

muscles, articular cartilage, menisci, ligaments, joint capsule, synovial lining, synovial fluid, burase

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30
Q

What is cartilage?

A

A dense connective tissue composed of solid phase (ECM), an electrolyte fluid, and relatively few cells.

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31
Q

Major ECM constituents of cartilage

A

large proteoglycans, noncollagenous proteins, small proteoglycans, collagen

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32
Q

What is 90% of the dry weight in cartilage?

A

Type II collagen and aggecran (large proteoglycans). Type II collagen forms a network that entraps proteoglyans.

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33
Q

What are attached to proteoglycans in cartilage?

A

Glycosaminoglycan side chains (GAG) side chains that bind water (70% of water)

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34
Q

What are the GAG sidechains made up of?

A

Chondroitin sulfate and keratin sulfate

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35
Q

What is hyaluronic acid?

A

Matrix component that binds proteoglycans together

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36
Q

What is aggrecan?

A

large keratin sulfate/chondroitin sulfate proteoglycan, provides a hydrated space filling gel contributes to cartilage strength

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37
Q

Types of cartilage

A

hyaline, elastic, fibrocartilage

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38
Q

Hyaline cartilage is found where

A

Synovial joints, fewer fibres

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39
Q

Elastic cartilage is found where

A

Nose, external ear, more fibres (elastic), cells tightly packed

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40
Q

Fibrocartilage is found where

A

menisci in the knee

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41
Q

Characteristics of fibrocartilage

A

Transitional state between true cartilage and fibrous connective tissue; collagenous fibers, minimal matrix; cells are embedded in the matrix between the fibers, but still in lacunae.

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42
Q

What does articular cartilage in synovial joints do?

A

Acts to reduce friction and abosrob shock; prevents bone on bone contact

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43
Q

How is cartilage in synovial joints nourished?

A

Avascular, so it is nourished by diffusion from vasculature of bone and synovial fluid

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44
Q

What surround articular cartilage?

A

Joint capsule

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45
Q

What is the synovium, and what does it do?

A

A soft tissue that lines the non-cartlaginous surfaces within joint cavities; expands and contracts during movement; secretes synovial fluid and is supported by microvessels immediately below lining cells at joint space surface –> nutrients for synovium and avascular cartilage

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46
Q

What are the components of synovial fluid?

A

Hyaluronan and lubricin

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47
Q

What does synovial fluid do?

A

Reduces friction between cartilage and other tissues in joint, lubricates and cushion. Enables exchange of nutrients with articualr cartilage

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48
Q

Where is synovial fluid found within a joint?

A

Fluid forms a thin layer at the surface of cartilage but also seeps into the cartilage

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49
Q

What is hydrodynamic lubrication?

A

Load induced compression forces fluid out of cartilage laterally and to surface, creating a protective, aqueous layer

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50
Q

What is boundary layer lubrication?

A

Lubricin binds to articular cartilage, retains a protective layer of water molecules, providing a slippery coating

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51
Q

What is squeeze film lubrication?

A

load applied –> synovial fluid pressurized, moves out and possibly into cartilage –> ncreased viscosity in fluid –>trapped fluid supports load and reduces friction

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52
Q

What is fibromyalgia?

A

A widespread, musculoskeletal pain accompanied by fatigue, sleep, memory, and mood issues. Chronic widespread pain disorder commonly associated with comorbid coiditions, including fatigue and nonrestorative sleep.

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53
Q

Causes of fibromyalgia?

A

Cause is not clear–genetics and environment (stress) may contribute. Centralized pain–sentral nervous system origin. Disturbances in autonomic and stress response systems. Abnormal processing of pain by CNS –> volume control set to high (levels of NT that facilitate pain transmission). Psychiatric conditions can co-exist, may have some origin such as early life trauma/stress

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54
Q

Manifestation of fibromyalgia

A

Diffuse, chronic pain throughout body, sensory, hyper-responsivenss. Migraine headache. Chronic fatigue, sleep disturbance. Irritable bowel syndrome. Depression. Restless leg syndrome. Temrpomandibular joint syndrome. Myofascial pain syndrome. Fibro “fog” – memory and mood difficulties

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55
Q

Modifiable risk factors for fibromyalgia

A

poor sleep, obesity, physical inactivity, poor job or life satisfaction, catastrophizing

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56
Q

Potential therapies for fibromyalgia

A

improve sleep patterns, weight loss, activity and exercise, stress reduction, cognitive behavioral therapy

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57
Q

Considerations for exercise prescription in fibromyalgia

A

Limit overuse of small muscle groups (i.e. overhead exercises), minimize eccentric portion, Strategies to increase adherence: self-monitoring, group exercise, action planning/coping planning

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58
Q

What is OA?

A

deterioration and loss of articular cartilage, thickening of the subchondral bone, bony outgrowths at joint margins, mild, chronic synovial inflammation

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59
Q

Mechanical risk factors for OA

A

low quadriceps strength, increased body weight (due to inflammatory environment), occupation, injury (ACL rupture, especially with meniscus tear, other disorders), anatomic abnormalities (genum varum or valgus, congenital hip sublumxation, acetabular displasia)

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60
Q

Metabolic risk factors for OA

A

obesity (adipokines —> proinflammatory), systemic inflammation may predispose people to OA, metabolic syndrome (advanced glycosylated end products (AGEs accumulation, oxidative stress. Hypertension (leads to subchondral ischaemia)

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61
Q

Symptoms of OA

A

pain, stiffness around joint, limited function. pain typically worsens with activity, lessens at night. Pain at rest or at night a feature of severe disease. Duration of morning stiffness shorter (<30 min). Pain and stiffness worse in damp, cool, rainy weather

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62
Q

Signs of OA

A

bony enlargement, tender at joint margins and at attachment of joint capsule and tendons, pain or limitation of motion related to osteophyte formation, joint surface incongruity, muscle spasm, and contracture. Joint instability: peri-articular muscle weakness or abnormal propriorecption. Joint locking out during ROM (loose bodies or fragments). Creptius. Local inflammation. Joint malalignment 50% of knee OA: varus common

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63
Q

Heberden’s Nodes

A

Enlarged end joints of finger (distal interphlangeal joints)

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64
Q

Bouchard’s nodes

A

Enlarged middle joints of finger (proximal interphalageal joints)

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65
Q

Turnover in normal cartilage

A

Matrix undergoes turnover via chondrocyte activity: production of enzymes (matrix metallopeoteinases, others) to degrade catilage. Synthesis of new collagen and proteoglycans, growth factors and MMP inhibitors (tissue inhibitor of metalloproteinases). Normal cartilage = low levels of synthesis and degradation –> cartilage volume maintained

66
Q

What happens with aging in NORMAL cartilage?

A

Glycosaminoglycans become shorter. Changes in [keratin sulfates]. Decrease in chondrocytes and capacity of proteogylcans to retain water –> altered biomechanical properties. Stress fractures of collagen network –> fissurse

67
Q

What happens to cartilage in OA

A

Mediators of cartilage destruction in OA include MMPs and pro-inflammatory cytokines (e.g. IL-1) —> degrading enzymes over-expressed relative to capacity to repair = net degradation —> loss of collagen and proteoglycans, decreased number of chondrocytes, decreased cartilage volume, fibrillation, erosion and cracking in superficial cartilage layer —> progress to deeper layers —> eventually large erosions

68
Q

Characteristics of early osteoarthritis

A

Areas of chondrocyte loss and increased proliferation and synthesis of matrix. Increased cytokine synthesis, prostaglandins, free radicals —> activation of chondrocytes —> increased synthesis of MMP and decreased TIMP. Microcracks in cartilage —> deep fissures and pitting. Subchondral bone demineralization with microfractures. edema

69
Q

Characteristics of late osteoarthritis

A

Decreased chondrocyte proliferation. Chondrocyte apoptosis. Fissures cause fragments of cartilage to detach. Exposed subchondral bone. Osteophyte formation. Sclerosis of subchondral bone (bone thickening). Persistent synthesis of proteinases and cytokines.

70
Q

Are the changes in cartilage associated with aging the same as OA?

A

NO!!!

71
Q

What are the two main mechanisms of drug treatment for OA?

A

control symptoms and disease modifying/specific to the disease

72
Q

What are the three type of treatment for OA that control symptoms?

A

Analgesics, NSAIDs, glucocorticoids

73
Q

Are analgesics anti-inflammatory, and do they slow the disease progression for oA?

A

NO

74
Q

What do analgesics do, and what are some examples?

A

Medicines that relieve pain. Over the counter medicins like Aspirin and Tylenol (acteaminophen)

75
Q

What COX enzyme is responsible for prostaglandins expressed in inflamed tissues?

A

COX2

76
Q

What COX enzyme is responsible for prostaglandins expressed in GI mucosa, kidneys, platelets, and vascular endothlelium?

A

COX1

77
Q

How do NSAIDs work?

A

inhibit one or both of COX enzymes. Effective for treating swelling, pain, and stiffness –> symptom control. No effect on disease course or joint damage

78
Q

What are the problems associated with using NSAIDs?

A

GI toxicity an issue, especially in older patient

79
Q

What are the adverse effects of using COX-2 specific inhibitor?

A

May reduce GI toxcity, but there are other adverse reactions (allergy, renal failure, CV). Can use a proton pump inhibitor to reduce gastric acid secretion

80
Q

Why are corticosteroids used in arthritis?

A

Potent suppressor of inflammtion. Effective for managing pain and functional limitations in active inflammatory joint disease. Not adequate as sole therapy. Can be taken orally or injected into joint. Can’t be taken long term

81
Q

Conditional recommendations for NOT using in knee OA?

A

Chondroitin sulfate, glucosamine, topical capsaicin. No recommendations for hyaluronic acid

82
Q

No recommendations for knee OA?

A

Participation in balance exercises, either alone or in combinations with strengthening exercises, wearing laterally wedged insoles, receiving manual therapy alone, wearing knee braces, using laterally directed patellar taping

83
Q

Strong recommendations for non pharmacological treatment for hip OA

A

CV or RT land-based exercise, aquatic exercise, weight loss

84
Q

Intra-articular injections of GC are conditionally recommended for what types of OA

A

knee and hip

85
Q

Topical NSAIDs are conditionally recommended for what type of OA

A

knee and hand only

86
Q

topical capsaicin is a conditional recommendation for what type of OA

A

hand OA only

87
Q

Oral therapy (acetaminophen, NSAIds, Tramadol) is conditionally recommended for what type of OA

A

all of them

88
Q

Conditional recommendations for non-pharmacological treatment of hand OA

A

evaluating ADL performance, provide assistive devices as needed, provide instruction in joint protection, instruction in use of thermal modalities for relief of pain and stiffness, provide splints for patients with trapexiometacarpal joint OA

89
Q

Conditional recommendation for NOT using intrac-articular therapies for hand oA

A

k;f

90
Q

Strong recommendations for non-pharmacological treatment of knee OA

A

CV or RT land based exercise, aquatic exercise, weight loss

91
Q

Conditional recommendations for non-pharmacological treatment of knee OA

A

self management programs, manual therapy with supervised exercise, pyschosocial interventions, medially directed patellar taping, medial wedge insole (lateral compartment OA), laterally wedged insoles (medial OA), instructions in use of thermal agents, walking aids as needed, tai chi

92
Q

Conditional recommendations for non pharmacological treatment of hip OA

A

self management programs, manual therapy, thermal therapy in combo with supervised exercise, pyschosocial interventions, instruction in use of thermal agents, walking aids as needed.

93
Q

Summary of exercise in knee OA

A

decreased knee pain by 1 point on a scale of 0 to 20. Increased knee function by 3 points on a scale of 0 to 68

94
Q

Summary of exercise in hip OA

A

may reduce pain slightly, may not improve physical funtion

95
Q

Strong rationale that weight reduction may:

A

delay progression, reduce symptoms, improve function, lower impact of comorbidities and reduces incidence

96
Q

Who are surgical candidates for knee replacements?

A

usually those who “fail” other treatments (no relief from other therapies despite trials), pain progressed to unacceptable (at rest or night pain), joint is structurally unstable, not yet developed muscle weakness, deconditioning, can medically withstand stress of surgery

97
Q

What is arthroplasty?

A

Total joint replacement. Surgical replacement of a damaged/diseased joint or joint components with a prosthetic joint or joint components. LAST RESORT for patients with severe knee OA. Replacement usually lasts ~10 years

98
Q

What is a tibial osteotomy?

A

Removal of a wedge shaped portion of tibia or add material. Change alignment and redistribute body weight. Transfer stress to a less worn area of the knee, helping to relieve pain. Treat a varus (bowlegged), deformity ar the knee resulting from past trauma or srugery, congenital deformity and/or degenerative disease. Candidates for tibial osteotomies may eventually require a knee repalcement

99
Q

Risk associated with surgery

A

risk associated with anesthesia, infection developing in the artificial joint (requires removal of the artificial joint and treatment of the infection), development of blood clots, loosening of the joint, can damage meniscus, ligaments, and patellar ligament and nerves

100
Q

After a total hip arthroplasty, what are the movements to be avoided in the first 6-8 weeks?

A

extreme bending (flexion) of the hip beyond 90 degrees, corssing legs, turning the operated hip inward or outward (internal/external rotation)

101
Q

Most common form of crystal induced arthritis?

A

Gout (uric acid crystals)

102
Q

Calcium pyrophsophate dihydrate arthritis?

A

Chondrocalcinosis or pseudogout or pseudo-arthritis or pseudo0rheumatoid arthritis. CPPD crystals present in synovial fluid. Overproduction of extracellular pyrophsophate, treat with NSAIDs or glucocorticoid

103
Q

Why does lead cause gout?

A

Damages kidneys and you to retain uric acid –> carried by the bloodstream to big toe or foot were the uric acid turns into needle like crystals

104
Q

Gout risk factors

A

Males, postmenopausal women, overproduction of urate from inherited enzyme defects, obesity, purine rich foods, accelerated ATP degradation, underexcretion of uric acid

105
Q

How is alcohol related to gout?

A

Ethanol accelerates ATP bbreakdown, increases uric acid (ATP –> ADP + AMP, AMP –> uric acid), guanosine in beer is catabolized to uric acid.

106
Q

What can cause underexcretion of uric acid ?

A

Thiazide diuretics, exogenous insulin, beta blockers, cyclosporine, hypertension (reduced renal blood flow), metabolic syndrome, obesity, renal failure

107
Q

treatment of gout

A

NSAIDs of glucocorticoids in acute gout. Urate lowering therapy, cessation of alcohol use, weight loss, replace thiazide diuretics with another anti-hypertensice

108
Q

Progression of gout

A

asymptomatic hyerurinecmia –> acute intermittent gout –> advanced gout

109
Q

Most common spot of gout?

A

first metatarsophalangeal joint

110
Q

What is RA?

A

A chronic, systemic, inflammatory disease. Inflammation of the synovium of joints. Joint damage, pain, loss of function, disability.

111
Q

What is the pathogenesis of RA and what causes its progression?

A

Pathogenesis is progressive inflammation of the synovium and destruction of joint architecture. Persistence and progression regulated by immune mediators.

112
Q

When is peak incidence of RA?

A

Between 4th and 6th decades…affects all ages, though

113
Q

Percentage of RA patients that have a monocylic course that ablates within 2 years?

A

20%, the rest will have polycyclic or progressive course

114
Q

Is there a genetic predisposition for RA?

A

Yes, multiple genes involved (dizygotic twin 6 times more likey, monozygotic twin 30 times more likely). Genetic basis not sufficient to explain trigger for disease. Many different genes involved, and each make only small contribution to disease susceptibility

115
Q

Risk factors for RA

A

2.5x higher in women, smoking, age

116
Q

Most common joints affected by RA?

A

Hand and wrist. MCP, PIP often involved…the DIPs are usually spared

117
Q

Percentage of joints affected by RA in the first year?

A

90% of joints

118
Q

What triggers an immune response?

A

Antigen/foreign cell

119
Q

What can an antigen be?

A

a virus, cells from another person

120
Q

What is an autoimmune disease?

A

Immune system responds to body’s own cells or tissues

121
Q

Body cells have what attached to them?

A

MHC/HLA complexes (major histocompatability complex or human leuokocyte antigens)

122
Q

What do killer T cells do?

A

Attack cells that have an antigen on them

123
Q

What do natural killer cells do?

A

Recognize foreign cells with no self-MHC complex

124
Q

What do helper T cells do?

A

Help to coordinate the immune response by stimulating antibody production, calling in phagocytes, activate other T cells

125
Q

What is auto-immunity?

A

An antigen-specific immune response to an auto-antigen that leads to disease. Immune system is launching an attack on its own body –> antibodies are produces and react against a body constituent, failure to recognize constituent as “self”

126
Q

What is a consistent feature of RA?

A

T-cells infiltrating the synovium.

127
Q

What is the auto-antigen in RA?

A

Not defined

128
Q

What two types of cells comprise the lining layer in normal synovium?

A

Macrophage like synoviocytes (MLS)-phagocytic. Fibroblast like synoviocytes (FLS)-systhesize matrix proteins (collagen, hyaluronan)

129
Q

What happens to the synovium in RA?

A

Increased lining cells (MLS and FLS) cuasing increased dpeth of lining (tissue proliferates), acts as a source of inflammatory cytokines and proteases, proliferating tissue into joint cavity and cartilage = pannus. Sublining –> edema, blood vessel proliferation (because blood supply is needed for proliferating tissue), accumulation of T and B lymphocytes, plasma cells. natural killer cells

130
Q

What is pannus?

A

Proliferating tissue into joint cavity and cartilage in RA

131
Q

What are the key features of a joint in RA?

A

Hyperplastic synovial membrane, infiltration of lymphocytes and macrophages, pannus infiltrates the cartilage and surrounding bone

132
Q

What are the 3 stages of RA?

A

1) Swelling of the synovial lining –> pain, warmth, stiffness, redness and swelling around joint 2) Formation of pannus –> rapid division and growth of cells –> thickening of synovium, covers cartilage, destroys joint capsule and bone. 3) Destruction of bone and cartilage: synovial and immune cells release enzymes, destroying cartilage. Synovial and immune cells release cytokines, RANKL –> bone erosion. Bone and cartilage destruction can cause involved joint to lose its shape and alignment, more pain, and loss of movement

133
Q

Cytokines involved in RA?

A

MLS, FLS, T cells and synovial cells produce pro-inflammatory cytokines (TNF alpha, GM-CSF, interleukins) and inhibitory cytokines suppress inflammation in part, but theyaare overwhelmed by the pro-inflammatory cells

134
Q

What do cytokines do in RA?

A

ACtivate chondroblasts to releast proteinases, which destroy the cartilage. Cyokines also stimulate osteoclasts, RANKL production by fibroblasts and T cells

135
Q

What happens to synovial fluid in RA?

A

Increase synovial fluid volume –> manifests as swelling. Increased neutrophils which release proteinases and cytokines

136
Q

How is cartilage destroyed in RA?

A

Chondrocytes, synovial cells (MLS, FLS), neutrophils are activated by IL-1, TNF alpha, IL-17 and immune complexes. Chondrocytes release enzymes (MMPs, collageneases, proteinases) that destroy cartilage. Protease inhibitors are present, but overwhelmed by enzymes doing degradation

137
Q

Steps in cartilage destruction in RA

A

Inflammation of synovium (pannus), leads to increase in synovial fluid volume, neutrophils, and T and B cells to the joint —> Increased cytokine production by T cells, B cells, synovial cells (MLS, FLS) –> Neutrophils, synovial cells, chondrocytes release destructive enzymes in response to IL 1, TNF-a, IL17, immune cells —> cartilage destruction

138
Q

Mechanism of bone erosion in RA

A

RANKL expression by T cells and FLS –> activation of osteoclasts (leads to bone erosion). Cytokine activation by osteoclasts

139
Q

What are the radiological findings in RA that are different than OA?

A

Bony erosions at joint margins (don’t see in OA, osteophytes in OA). Joint space narrowing (also see in OA)

140
Q

Lab tests that can be used to help with diagnosis of RA, although no lab test, histological finding or radiographic feature confirms RA

A

Rheumatoid Factor, erythrocytes sedmenation rate and CRP

141
Q

2 categories of articular manifestations in RA

A

1) Reversible signs and symptoms related to inflammatory synovitis 2) Irreversible structural damage caused by synovitis–begins in 1st and 2nd year (caused by every cycle of synovitis)

142
Q

Synovitis symptoms tend to fluctuate, but structural damage progresses linearly as function of prior synovitis

A

Synovitis = inflammation of synovial membrane

143
Q

Morning stiffness associated with RA?

A

> 2 hours (OA is 5-10 min)

144
Q

Structural damage in RA to the joint

A

Cartilage loss, erosion of peri-articular bone, irreversible (symptoms that fail to respond to aggressive therapy (e.g. corticosteroid injection won’t make symptoms due to joint damage feel any better), radiographs show loss of joint space, bone on bone creptius—high pitches screehe detectable on palpation or auscultation

145
Q

Determinants of disease outcome in RA

A

RF or other antibodies, low SES or educational status, disability indicators, joint erosions, elevated CRP and ESR, family history of severe RA, female gender, genes

146
Q

Secondary complications of RA

A

Increased risk of CVD and death, disability, drug side effects, increased risk of fracture (independent of BMD)

147
Q

Two groups of drug therapy for RA

A

Control symptoms (NSAIDs and Analgesics), and those that limit joint damage (Disease Modifying Anti-Rheumatic Drug)

148
Q

2 types of DMARDs

A

Traditional DMARDS and biologic agents

149
Q

What do DMARDs do?

A

Prevent joint erosions and damage. Control active synovitis and other features of disease. No evidence that DMARDs can “heal” disease. Should be used when diagnosis is established. Vary greatly in mechanism of action. Can be used with NSAIDs or corticosteroids.

150
Q

What do traditional DMARDs?

A

Target cellular components (B and T cells) –> target cellular components of immune/inflammatory response (i.e. B cell and T cell for RNA/DNA production in immune cells),

151
Q

Side effects of traditional DMARDs

A

Can affect bone marrow and liver, therefore, requires regular WBC checks and liver function tests

152
Q

Most common DMARD

A

Methotrexate (well established long-term efficacy)

153
Q

What are biological agents for RA?

A

Derived from or resemble naturally-occurring molecules. Genetically engineered to target cytokines (anti TNF-alpha, antibody agents, IL-1 receptor anatagonists). Blocks message to increase inflammatory cells

154
Q

Side effects of biologic agents

A

Infection, reports of fatal infections and TB

155
Q

Why are biologic agents such as Inflixmab, Humira, and Enbrel used sparingly?

A

Very expensive, used when other treatments are not effective and often used in vombo with methotrexate

156
Q

Surgery in RA

A

Tendon repair and transfer, carpel tunnel release, total joint replacement, arthrodesis (fusion) of ankles, wrists, fingers, and toes. Stabilization of unstable cervical vertebrae

157
Q

When do you refer for surgery in RA

A

Refer for surgical opinion when, despite non-surgical management the following persist: persisent pain due to joint or soft tissue damage, decreasing joint function, joint in unstable, deformity progresses, persistent synovitis in joint, can withstand surgery, not deconditioned

158
Q

What are your therapeutic goals during an RA flare-up?

A

Pain reduction, modify activities/use, prevent atrophy

159
Q

What are your therapeutic goals be as an RA flare-up resolves?

A

Increase ROM, maintain strength, prevent arophy

160
Q

What are your therapeutic when RA is stable?

A

Maintain/increase CV fitness, maintain/increase muscle strength

Fall 2014 (3 decks)

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