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84 Cards in this Set
- Front
- Back
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where does Crohns disease aaffect |
usually ileo-caecal region but any part of bowel from mouth to anus |
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what are the symptoms of crohns |
diarrhoea - sometimes bloody pain weight loss |
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how many people does Crohns affect in the UK |
5/100000 |
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what is the histology of crohns |
swollen and red ulcers and lymphocyte infiltration |
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what does radiology show for crohns |
inflammatory mass and swelling and pain and anastomotic stricture |
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what area does ulcerative colitis affect |
colon |
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what is the difference between crohns and UC |
UC may lead torupture and peritonitis |
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what is the histology of UC |
loss of surface layer, glandular distortion, inflammation, leukocyte and macrophage infiltration, crypt abscess may lead to rupture |
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when does Crohns normally begin |
in young adults |
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why are you more likely to need surgery the longer you have disease |
the longer the incidence of complication |
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why does risk of cancer increase |
due to chronic inflammation of the bowel |
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what is used to treat it |
5-aminosalicylic acid steroids azathioprine/methotrexate surgery infliximab |
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what are steroids used for |
acute flare ups |
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what are the benefits of steroids |
can avoid surgery 82% go into complete remission or partial remission |
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how are steroids administered |
via an enema |
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why are steroids administered up the bum |
increase local concentration and not as much absorbed into the blood so localised response |
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when can you not give an enema of steroids |
small bowel Crohn's |
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what are the side effects of steroids |
skin thinning and purpura acne CV- hypertension, perturbations of serum lipoproteins, premature atherosclerotic disease, arrhythmias with pulse infusions diabetes mellitus |
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when is 5-ASA better than steroids |
when applied topically |
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what are the adv and disad of infliximab |
4 weeks post treatment nearly cured can give 4-8 years of disease free life but needs to be given regularly can have horrible side effects |
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what is the most common autoimmune disease in humans |
RA |
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what is the prevalence of RA |
0.5-1% |
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what is the female to male ratio of RA |
3:1 |
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what does RA first affect |
small joints of hands then to larger joints |
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how many patients have radiographic damage within first 3 years |
70% |
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how many patients are disabled after 20 years |
80% |
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how much is the life expectancy reduced by for RA |
3-18 years |
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why do people with RA die younger |
also affects other organs e.g. hearts, kidneys |
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what is the histology of RA |
synovium has B and T cell infiltration CD4+T cells macrophages infiltrate massive hyperplasia of intimal lining |
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what pathways drive most of the damage in RA |
IL and TNF |
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what does TNF activation affect |
many cells in both and synovium inc. osteocytes osteoclasts etc. |
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what is the result of osteoclast degradation |
bone resorption and bone erosion |
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what is the result of synoviocyte degradation |
joint inflammation leading to bone resorption, cartilage degradatoin and pain and joint swelling |
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what is the result of chondrocyte degredation |
joint space narrowing |
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outline IL-2 pathway |
antigen binds to TLR on APC APC expresses CD80 and MHCII T cell binds CD80+CD28, MHC II and TCR APC sends IL-12 to T cell T cell activated and releases IFN-Y and IL-2 which activates T cell and Th1 cell Th1 costimulates B cell th1 releases IFN-Y and IL-17 to macrophages macrophages send back IL-15 and 18 |
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what are the factors of mediation of the pathological process of RA |
autoimmune response with auto abs and immune complexes t-cell-mediated antigen-specific responses t-cell-independent cytokine networks |
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what is certain about the pathology of RA |
t cells are a major driving force NF-kB activated in synovium and regulates genes involved in inflammation MAP kinases are activated in rheumatoid tissue - |
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what genes are involved in inflammation |
TNFalpha IL-1 IL-2 IL-6 IL-8 iNOS and COX-2 |
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what are MAP kinases |
key regulators of cytokine and metalloproteinase production |
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what drugs are used for symptomatic treatment |
NSAIDs |
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what drugs are used in early RA in combo with NSAIDs |
second line drugs - DMARDs |
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why are DMARDs used |
prevent erosive damage if patient intolerant to NSAIDs extra-articular manifestations of RA poor response to NSAIDs |
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why are COX-2 inhibitors not used for RA |
caused heart damage |
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what are DMARDs |
disease modifying anti-rheumatoid drugs |
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what are the effects of DMARDs |
reduce rate of disease progression modify long term outcome of disease |
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what is the mechanism of DMARDs |
unclear but long term depression of inflammatory response may be implicated |
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how long before improvement is seen with DMARDs |
3 months |
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what is first choice DMARD |
methotrexate |
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what is the mechanism of methotrexate |
inhibition of enzymes involved in purine metabolism resulting in - accumulation of adenosine - inhibition of T cell activation - suppression of adhesion molecule expression by T cell |
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what are the side effects of methotrexate |
blood dyscrasias liver cirrhosis peptic ulceration , UC, diarrhoea, ulcerative stomatitis |
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what is blood dyscrasias caused by |
bone marrow suppresion so increased chance of infection and less platelets so increased chance of bleeding and bruising |
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what is sulphasalazine |
sulphapyridine combined with salicyclate hydrolysed by gut bacteria to sulphapyridine and 5-ASA |
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what does sulphapyridine do |
reduces absorption of antigens from colon that may promote joint inflammation |
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what does 5-ASA do |
reduces synthesis of inflammatory mediators |
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what are the side effects of sulphasalazine |
GI reversible decrease in sperm count sulphonamide idiosyncratic blood dyscrasias anaphylaxis |
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what is Gold |
aurothiomalate and auranofin |
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what are the possible mechanisms of action of gold |
inhibit lymphocyte proliferation inhibit release and activity of lysosomal enzymes decrease production of O2 toxic metabolites from phagocytes inhibit chemotaxis of neutrophils inhibit induction of IL-1 and TNF-alpha -binds to tissue proteins and accumulates widely inc. in synovium of inflammed joints |
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what are the side effects of Gold |
can be serious - blood disorders inc agranulocytosis, aplastic anaemia, skin rashes, diarrhoea and glomerulonephritis |
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when are steroids used |
early on in RA and then as disease progresses put on DMARDs |
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how are steroids applied for individual joints |
intra-articular injections |
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in the active disease how are steroids applied |
short courses of oral prednisolone |
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what is the standard steroid therapy |
combo of low dose glucocorticoids plus sulphasalazine/methotrexate |
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what are the mechanisms of corticosteroids |
immunosuppresant decrease transcription of IL2 TNF alpha IFN gamma |
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what side effects do steroids have |
if injected non if oral systemic |
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name two current biologics |
etanercept infliximab |
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what are the targets of etanercept and infliximab |
TNF alpha |
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why are biologics not used as first response |
expensive |
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what are the guidelines for biologics |
-failed 2 standard DMARDs (inc MTX) for at least 6 months -half will response to combo of infliximab and MTX for at least 12 months |
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what are the common side effects of anti-TNF biologics |
nausea low grade fever anorexia |
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what are the contraindications of TNF biologics |
pregnancy or breastfeeding chronic leg ulcers previous TB septic arthritis sepsis of joint prosthetic persistant chest infections indwelling urinary catheter MS malignancy |
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when do you need to withdraw biologics |
malignancy drug intolerance pregnancy severe infection inefficacy |
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what is certolizumab pegol against |
anti TNF |
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what is tocilizumab against |
anti IL-6R |
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what is ofatumymab against |
anti CD20 |
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what is golimumab against |
anti TNF |
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how does acute arthritis cause gout |
deposition of urate crystals in synovial tissues |
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how is gout a metabolic disorder |
plasma urate conc increased due to overproduction of purines and/or imparied excretion of purine |
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what is the pathology of gout |
crystal deposition --> kinin release/generation of LTB4 --> phagocytic neutrophil activation --> free radical formation --> cell damage and lysis |
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how can you treat gout |
inhibit uric acid synthesis increase uric acid excretion (probenecid) inhibit inflammatory cell migration into joints give anti inflammatory / analgesic drugs (NSAIDs) |
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outline the formation of uric acids |
nucleic acids -> overproduction of purines ->hypoxanthine -> xanthine -> uric acid |
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where does xanthine oxidase act |
between hypoxanthine and xanthine and uric acid |
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what drug inhibits xanthine oxidase |
allopurinal |
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what drugs increase excretion of uric acid |
probenecid and sulphinpyrazone |
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what drug inhibits leukocyte migration into joints |
colchicine |
