joint disease Flashcards
Synovial joints
Diarthrodial joints
Allow gliding facilitated by lubricated cartilaginous surfaces
hyaline cartilage on articular surface functions as an elastic shock absorber and spreads weight across surface of joint, friction free surface along with synovial fluid, Avascular, composed of type 2 collagne water and prtoepglycans and chondrocyte,
Synovial cavity: synovial cells line synovial cavity: cuboid cells 1-4 layers thick, produce synoviat fluid reve debirs and regulate the movement of solutes from capillaries into synovial fluid, not present over articular cartilage
Synovium: viscous filtrate of plasma containing hyaluraonic acid
Arthritis
Generic markers of inflammation: ESR(rate at which blood cells settle, CRP, anemia, leukocytosis
Serology: RFm CCP, ANA
Extra synovium
Sedimentation Rate (ESR)
Sed rate elevation results from infection malignancy, autoimmune/inflammatory conditions
Sed rates slow to change
Some things that falsely elevate ESR (End stage renal disease, anemia–less RBs to push each other down, obesity, age
Things that decrease ESR: fibrinogen is low, polycythenia vera, sickle cell, spherocytosis
CRP
Small molecule binds to dying cells/pathogens
Rapid rise within hours of tissue injury
Synthesized in liver, very high CRP=bacterial infections
high sensitivity CRP (hsCRP) measures the same molecule just an assay that can detect lower concentrations= cardiovascular disease
RF and anticyclic citrullinated peptide Ab (CCP) and ANA
RF: autoAb bind Fc region of human IgG (70% sensitivity for RA), 80% specific for RA
False positives: hep C, SJS, biliary cirrhosis, multiple myeloma, normal 4% of pop
CCP: 70 % sensitive for RA, >90 specific for RA
ANA: low in 5% of normal but its low in RA
Gout
Very inflammatory arthritis linked to metabolic disorders resulting in elevation of blood uric acid (hyperuricemia) and proinflammatory crystals in the joint. During acute gout flare may not have hyperuricemia
Approximately 4% of US:can be normal BMI, overweight
men> women
Acute: abrupt onset of severe pain, mostly monoarticular in bid toe, exam shows synovitis w/redness, self limited and usually resolves in 8-10 days
If chronic: polyartivualar and destructive
Tophaceous gout patters, urate encrustsarticular surface and forms deposits that destroy cartilage (surrounded by lympocytes, giant cells and fibroblasts)
Hyper uricemia pathophysiology
over production (10%)- inherited enzyme defect, myeloproliferative disorders, purine rich diet, alcohol
Underexrection (90%) renal failure, metabolic syndrome, diuretics, alcohol
Gout treatment
W/i first 24 hrs: indomethacin and naproxen (no aspirin) in pts who cant take NSAIDs give cortico steroids- short term, adverse effects with extended use
Colchicine
gout treatment
No effect on uric acid excretion
Antimitotic- Binds to microtubules in inflammatory cells ie PMNS – inhibits PMN activation and migration
Pharmacokinetics: oral, rapid absorption, deposits in tissue stores/forms complex with tubulin (large VD) metobilised vi CYP450 substrate for p glycoprotein that spits drugs out
SE: adverse effects, significant, narrow therapeutic window, GI,
Contradindicated: hepatic/renal disease, elderly pt, cyp3a4 or p-gp inhibitor co administered
Use: acute gout attacks (w/in hours prophylactically in pt with chronic)
Allopurinol
MOA: inhibits terminal steps in urate biosynthesis, blocks xanthine oxidase
plasma uric acid conc. decreases, uric acid crystal dissolve
Pharmacokinetics: metabolized to active compound, structural analog of hypoxanthine, converted to oxypurinol by aldehyde oxidoreductase
Long t.5
SE: hypersensitivity, acute gout attack (mobilizes stores of urate so give the drug with cochicine or NSAID)
Use: prevention of primary hyperurrecemia of chronic gout
Febuxostate
non purine xanthine oxidase inhibitor
More potent than allopurinol, es in pt with renal impairment
Less adverse effects, CV side effect
Pegloticase
MOA: uricase absent in humans, converts urate to allantoin (inactive water soluble form. its a recombinant form of uricase
SE: infusion site reactions, gout flare, immune response
Probenecid (increases urate excretion by competing with renal tubular acid transporter so that less urate is REAB), some GI SE ineffective in pt with renal insufficiency, or kidney stones
major drug interactions of gout medication
allopurinol/febuxostate: inhibit metabolism of azathioprine and mercaptopurine so increased toxiticity
colhicine: susceptible to inhibition of cyp3A4 metabolism and p-gp transport
Probenecid: interference with renal excretion of drugs that undergo active tubular secretion
Rheumatoid Arthritis
Inflammatory symmetric chronic polyarthritis
Immuno disease (both T and B cells)
Genetic predisposition (DR4 and DR1) 1 % of population, women>men
Pathogenesis: DC cells present Ag to T cells, activated T cells stimulated the production of B and T cells, B cells produce plasma cells that form Rheumatoid Abs, Helper T Cells activate Macrophages and cytotoxic T cells, T cells, macrophages and cytotoxic T cells produce cytotoxic cytokines (TNF a, IL1, IL6) and PGs that cause joint inflammation synovial proliferatice and bone cartilage
Gradual onset of joint pain, swelling and inflammation for more than 6 wks, symmetrical in nature and often involves sm joints, morning stiffness ,elevated inflammation serology
Swan neck deformity, boutiniere deformity, RA nodules
Rheumatoid vasculitis, interstitial lung disease, premature coronary artery disease, SJS, feltys syndrom (big spleen less WBC
Pathology of rheymatoid arthritis
makes a pannus
Chronic papillary synovitis (CD4 T cells, plasma cells and macrophages, giant cells (frequently forming lymohoid follicles), accompanied by synovial cell hyperplasia –>papillary nodules
PMN and fibrin on joint surfaces in acute phase
Hyperplastic inflamed synovium extends over articular surface–> pannus
Leads to destruction of bone (osteoclasts), fusion of joiny ankylosis,
