68.OA Flashcards
define arthritis
disease process within the synovial jointClassified as noninflammatory vs inflammatorybut all display some form of inflammation
“noninflammatory” arthritis
- OSTEOARTHRITIS (DJD, OA, osteoarthrosis)almost always SECONDARY20% adult dogs; 60% adult cats (can be primary in cats)key tissue = ARTICULAR CARTILAGE2. Traumatic3. Coagulopathic
Etiology of osteoarthritis
G-A-B-O-G-E1. Genetics: multiple genes2. Age: incr age= less aggrecans, slow responsiveness to anabolism3. BW: Boxer w hi birthweight, incr risk hip dysplasia/CCL4. Obesity: Lab cohort study signs of OA/HD w ad libitum feeding 42 vs 4% @ 2 YO 5. Gender: neutered boxer 1.5 x risk HD; neutering male/female incr risk CCLR6. Environment: leash exercise (exercise increases VI, PVF in OA patients), diet, housing (slippery floors)
van Hagen et al Incidence, risk factors, and heritability estimates of hind limb lameness caused by hip dysplasia in a birth cohort of Boxers. Am J Vet Res. 2005
neutering at least 6 months before making a dx of clinical hip dysplasia influenced the risk of clinical HD developing over timeneutered Boxers were 1.5 x more likely to develop clinical HD
Beraud, R, Moreau, M, Lussier, B Effect of exercise on kinetic gait analysis of dogs afflicted by osteoarthritis. Vet Comp Orthop Traumatol 2010
force platform GAcontrol and OA dogsbaseline and post exerciseno change with control grouppeak, impulse, and propulsion vertical force values were sign lower post exercise (exercise actually improved limb use)
central theme to pathogenesis of osteoarthritis
alterations in metabolism/morphology articular cartilagechanges in subchondral bone metabolism/architecture (sclerosis)osteophyte/enthesiophyte formationsynovial inflammation and fibrosis
3 overlapping stages of articular cartilage pathogenesis in OA
- ECM degrades, incr water content, decr aggrecan/P size, damage to collegen network–>reduce compressive stiffness2. chondrocytes compensate–prolif (anabolic–thickness stage)3. chondrocytes depleted, complete loss of cartilage tissue (ulcer, eburnation, erosion)
what substance/protein br eaks down type II collagen
intact triple helix of type II collagen can be degraded by MMP 1 and 13 (+/- 8, 14)and aggrecanases
arthroscopic outerbridge classification for OA
0 normal cartilageI softening and swelling of cartilageII fragment/fissuring of area < 0.5 inIII Fragment/fissuring of area > 0.5 inIV cartilage erosion/ eburnated bone
surgical mgmt for OA
- joint debride/micropick (abrasion chondroplasty)–stimulate fibrocartilage2. joint replacement (hip, elbow, knee)3. arthrodesis/salvage excision arthroplasty4. amputation5. euthanasia
normal synovial fluid analysis
< 2n x 10^9 TNCC94-100% mononuclear0-6 % PMN
OA synovial fluid
< 2-5 x 10^9 TNCC88-100% mononuclear0-12 % PMN(similiar to normal OA) mild inflammatory
RA (erosive) synovial fluid
< 8-38 x 10^9 TNCC20-80% mononuclear20-80 % PMN
nonerosive IMPA synovial fluid
< 4-37 x 10^9 TNCC5-85% mononuclear15-95 % PMN
infective arthritis synovial fluid
< 40-267 x 10^9 TNCC 1-10% mononuclear90-100% PMN
medical mgmt for OA
- weight mgmt-exercise, rx diet, rx (microsomal triglyceride transfer P inhibitor)2. exercise–regular, moderate, controlled3. RX–symptom (NSAID) vs structural (stop cartilage damage) rx4. Nutrition (nutraceutical vs functional food J/D)5. Mesenchymal (multi potent) stem cell tx
MOA of NSAIDs
- Cyclooxygenase (COX) inhibitionwith COX inhibition, AA does not convert to PG (PGE2) thus no vasodilation, edema, incr pain noted2. Lipoxygenase (LIPOX) inhibitionif COX path is blocked, incr LIPOX path to make leukotrienes (proinflm, incr PMN, hyperalgesia)Ideally, NSAID would be LIPOX/COX inhibitors
COX 1 vs COX 2
COX 1 constitutive, in many tissues (makes PGs important for normal physiologic function)COX 2 inducible, upregulated w inflm; IS CONSTITUTIVE in kidney, brain and is cytoprotective to GI mucosaselective inhibition of COX 2 without affecting COX 1 will allow analgesia WITHOUT unwanted side effects of Cox 1 inhibitionGOAL: inhibition of COX2 at lower concentration than the concentration needed to inhibit COX1 (either a HIGH COX1:COX2 ratio or LOW COX2:COX1 ratio) pg 1057 Boothe
adverse effects of NSAIDs
GI–vomiting, diarrhea, inappetanceimpaired platelet activity–decr thromboxane (COX 1 selective action)nephrotoxic–PGE2/PGE1 maintain renal BF (COX 1 and COX2 actions)hepatotoxic
prostaglandins and their role for GI integrity
NSAIDS inhibit COX and decrease PG synthesisnatural GI integrity protected by PG mediated: 1. bicarbonate rich mucus2. gastric epithelial cell turnover at apical membrane3. high blood flow to release bicarbonate and neutralize any acid (decr H); also brings oxygen and nutrientsPGE2 maintains mucosal layer, mucus layer, blood flow, and gastric acid production and is made through COX 1 path
carprofen
propionic acid derived NSAIDconsidered COX 2 selective (COX1:COX2 ratio = 17)
deracoxib
coxib derived NSAIDgreater bioavailability with food
etodolac
indole acetic acid derived NSAIDboth COX1 (»>) and COX2 inhibitionlong serum half life–> 10-15 mg/kg PO SIDbiliary excretion and enterohepatic recirculationAdditional side effect: KCS
firocoxib
pyridylsulfone derived NSAID (previcox) COX 2 selective5 mg/kg PO SIDcan be given with or without food
ketoprofen
propionic acid derivative NSAIDCOX1 selective (CONTRAST TO CARPROFEN)0.25 mg/kg PO SID
meloxicam
oxicam derived NSAIDCOX 2 selectiveratio COX1:COX2 = 3 NOT for cats in USAdog 0.2 mg/kg loading dose PO SID followed by 0. 1 mg/kg PO SID
robenacoxib
coxib derived NSAIDhighly COX 2 selectiveCOX1:COX2 ratio 140biliary and renal excretionhigher bioavailability WITHOUT food
COX and LIPOX inhibitor NSAID with approval in EUROPE
TEPOXALINnonselective COX and LIPOX inhibitor10 mg/kg PO SID for up to 28 days10% GI side effects
amantadine
NMDA receptor antagonist3-5 mg/kg PO SIDneuropathic painstudy with meloxicam only showed slight benefit of amantadine added to regime–subjective criteria
gabapentin
GABA analogue– not liscened10 mg/kg PO TID dog 5 mg/kg PO TID cattaper down to avoid rebound painneuropathic pain
acetominophen
centrally acting analgesicNO USE IN CATS10-15 mg/kg q8-12hr DOGmaybe modulates serotonin in descending inhibitory pathways of paintoxicity in dogs >100 mg/kg
preferred intraarticular steroids
methylprednisolonetriamcinolonelong lasting for IA injectionrisk cartilage damage (controversial)
structure modifying agents for OA treatment
Polysulfated glycosaminoglycan (Adequan) 2 mg/lb IM twice weekly for 4 weeksmay maintain chondrocyte viability/prolif, protect ECM degradation
nutritional mgmt for OA
chondroitin sulfate –poor bioavail (5%), insufficient evidence, may not reach articular surfaceglucosamine–90% bioavail, incr protein and aggrecan synthesis; reaches articular surfacePUFA (contain more than 1 carbon -carbon double bond): linoleic (6), linolenic (3)3-FA may decr mRNA for proteinases and MMPs
types of inflammatory arthritis
- IMPA–erosive ( RA, PA of GH, feline chronic progressive PA)–nonerosive: IMPA (I-idiopathic, II-reactive, III-GI, IV-neoplastic), drug induced (sulfonamides/Dobies); SLE, Sharpeis/Akita breed related arthropathies2. infective arthropathy3. crystal induced (Ca, urate, hydroxyapatite)
rheumatoid factor
IgM (and IgA) autoantibodies against Fc portion of IgGserology for presence of these Ab aids in dx but may also be raised with other chronic inflammatory diseases
MOA of bacterial infective arthropathy
- hematogenous spread (second most common)2. direct penetration/trauma3. local spread from tissues (most common)dog most common: Staph intermedius, Staph aureus, beta hemolytic Strepcat: pastuerella, bacteroides
most frequent cause of infxn (infective arthropathy) in dogs/cats
post op infection following articular surgerytarsus, stifleex. 6.1% after TPLO surgery within 6 months; decr risk with using suture over staples and post op Ab administration but wound infections leading to osteomyelitis or septic arthritis are uncommon
T/FNerve endings are present on articular cartilage
FALSE free nerve endings are present in all structures of the joint EXCEPT articular cartilage
radiographic features of OA
SSS EE I Osoft tissue swellingsubchondral sclerosis *subchondral cystEffusionenthesiophytosisintra articular mineralizationosteophytosis * (usually at bone/cartilage junction)
MOA of bone scintigraphy
technetium is linked to diphosphonate carrierthe diphosphonate binds hydroxyapatite crystals and recently formed bone has large crystals for the carrier to bind”hot spot”
codeine
mu agonist5-10% convert to morphinealone schedule IIwith APAP schedule III
MOA of essential poly unsaturated fatty acids
PUFA (contain more than 1 carbon -carbon double bond): linoleic (6), linolenic (3)1. components in cell membranes2. involved in lipid transport3. serve as precursors to eicosanoid formation which regulates inflammatory process3-FA may decr mRNA for proteinases and MMPs and increase PVF days btwn days 0-90 on diet with hi omega 3 and owners subjectively thought they improved
idiopathic or type I IMPA (nonerosive)
accounts for 50% of IMPA usually carpi/tarsi affectsystemically can have pyrexia, lymphadenopathymost dogs respond well to initial immunosuppresive therapy (prednisone, leflonomide, azathioprine) BUT 31% relapse
diagnosis of SLE (non erosive inflammatory IMPA) with multi systemic dz
ANTINUCLEAR ANTIBODY TITERpyrexia with polyarthropathy+/- skin lesions (mucocutaneous junction)+/- meningitis+/- ophtho signs+/- hemolytic anemia +/- glomerular diseasetiters >160 somewhat guarded prognosis with immunosuppresive therapy
how many joint fluid samples are recommended to aid in diagnosis of IMPA
3 fluid samples from different joints
which drug and dog breed has the most apparent association with IMPA
sulfonamidesDoberman Pinschers
joints most commonly affected with IMPA vs septic arthritis
IMPA —carpi, tarsiseptic –elbows, stifles, carpus
treatment options for septic/infective arthritis
- joint aspiration2. joint irrigation3. arthrotomy, lavage4. arthroscopy, lavage5. synovectomy6. systemic Ab7. local Ab 28 d then recheck cytology8. Combo
According to Vanderweek JVIM 2012, the efficacy of nutraceuticals in dogs is poor with the exception of what
diets supplemented with omega 3 FA
two breed related IMPA (non erosive)
Akitas Sharpei
rheumatoid arthritis pannus
destruction of the articular cartilage and subchondral bone associate with an invasive tissue in jointsstifle>carpus>hip>elbow>tarsus
three types of erosive IMPA
- RA2. PA of GH3. Feline chronic progressive PA
criteria for diagnosing bacterial infective/septic arthritis
- typical hx and clinical signs2. synovial fluid cytology >40% PMN and high TNCC3. + culture (use blood cultures, sample >1) can get FN
