Unit 3 Rheumatology Flashcards Preview

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Flashcards in Unit 3 Rheumatology Deck (17)
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Abnormal NTP pyrophosphohydrolase enzyme activity and possible mutations of the ank gene result in increased levels of extracellular pyrophosphate (PPi) that precipitate with calcium forming calcium pyrophosphate dihydrate (CPPD) crystals in mid-zonal cartilage layers.
-associated with release of calcium pyrophosphate dihydrate into joint space
-involves larger joints like knee
-joint trauma, old age, metabolic diseases,
-labs: CPPD crystals (blue rhomboid)
-tx: no way to remove CPPD crystals from joints


Most common cause of hyperuricemia.

-uric acid is product of purine metabolism



-Loss of cartilage space and subchondral bony sclerosis
-starts in cartilage
-IL1, TNFa, IL6, IL17, IL18, prostaglandins, complement, adipokines, and NO may be present
-chondrocytes overproduce MMPs
-early aggressive OA may be caused by genetic mutation in type 2 collagen
-non inflammatory- type 1 fluid (200-2000 WBC)
-S&S: pain inc. with mobility, osteophytes (bony spurs), lack of systemic joint involvement, pain improved with rest, morning stiffness <30 min,
-DIPs involved (NOT MIPs)
-heberdens= distal
-bouchards= proximal
-risk factors: obesity, trauma, over 40yo
-lab: no specific test, imaging shows dec. joint space
-tx: ideal drug would target metaloproteinase (chondrocytes) to inhibit cartilage destruction, also cytokine inhibitor


CD4+ T Cells

-produce IL2 and IFNgamma


Rheumatoid Arthritis

-macrophages secrete IL1, TNFa, also important are IL6, IL17, IL8
-synovium is inflamed first
-autoantibody produced by plasma cells in synovial tissue then enters synovial fluid and binds Fc of IgG- leads to complement activation and neutrophil attraction
-S&S: involves MIPs (DIPs often spared), morning stiffness, joint warmth and swelling, tenderness, limited motion, rheumatoid nodules
-more common in women, more common in elderly
-lab: RF, inc. ESR, anemia, CCP antibodies, citrullinated proteins, >2000 WBC, dec. complement and glucose, symmetric loss of joint space, soft tissue swelling
-tx: NSAIDS, DMARDS, methotrexate, anti TNFa, physical therapy, surgery
-RF-IgG complexes are pathogenic- lead to rheumatoid nodules


cytokines in rheumatoid synovium include:

IL-1 and TNFα that induce local release of collagenases and other neutral proteinases from synovial fibroblasts and chondrocytes


molecular mimicry

autoantibodies can be generated through the initial stimulation by foreign antigens, and then cross react with structurally similar self-antigens


illicit help



seronegative spondyloarthopathies

-*hallmark is enthesitis (enthesis of bone is inflammed)
-*associated with HLAB27 (2% but 20% if also have first degree relative)
-back pain
-reactive arthritis
-bowel disease
-psoriasis vulgaris
-alkylosing spondylitis
-*inc. expression TNF
-*unknown infectious antigen in genetically susceptible host


Immune Complex Mediated Vasculitis







-crystals initially interact with synovial lining- activation of monocytes and mast cells
-initial recognition of MSU crystals by TLR2/TLR4
-TNFa, IL6, IL8, complement, ROS
-phagocytosis of crystals by PMNs results in PMN lysis with release of proteolytic enzymes
-*IgG binding to crystals promotes phagocytosis initially
-*apolipoprotein B coating inhibits phagocytosis
-MSU crystals activate NLRP3 inflammasomes which activates caspase 1, resulting in IL1B production
-GENETICS: X linked inc. PRPP synthetase, or partial dec. HGPRT
-S&S: come and go, asymptomatic hyperuricemia, acute gouty arthritis (MTP joint- podagra), intercritical gout, chronic tophaceous gout
-more common in men, elderly, obese, diabetics, underexcretion of uric acid
-labs: diagnosed with arthrosintesis MSU crystals (needle shaped yellow), negatively birefringent
-tx: lifestyle changes, NSAIDS, allopurinol or febuxistat to prevent xanthene oxidase from turing into uric acid


SLE (lupus)

-chronic, systemic autoimmune disease (T AND B cell process)- type 2 and type 3
-antibody responses to autoantigen are antigen-driven and require CD4+ cells
-B cell activation by T cells: peripheral and self-reactive
-polygenetic: HLA-DR3, C4A null alleles (STRONGEST risk association)
-*antiphospholipid antibodies inc. clotting
-S&S: malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serosis, renal issues, CNS issues,
-more common in young women, more common in hispanic and black women,
-labs: ANA (not specific for SLE) (multiple nuclear antigens), Coomb's test
-tx: avoid triggers like sun, NSAIDS, anti B cell antibody, IVIG


Reactive Arthritis

-lower extremity arthritis
-hx of infectious diarrhea
-sausage digits
-bacterial environmental triggers
-molecular mimicry hypothesis
-arthritogenic peptide hypothesis
-HLAB27 heavy chain theory: NK cell activation
-unfolded protein hypotheses: ER stress response
-Th2 (IL4, IL10) response hypthesis: bacterial persistence
-can't see, can't pee, can't climb a tree: Reiter's Syndrome


Alkylosing Spondylitis

-inc. expression of TNFa in synovium
-HLAB27 is 2% chance of AS
-HLAB27 with first degree relative with AS risk is 20%



-palpable purpura
-inflammation within vessel wall resulting in damage to vessel integrity/flow
-large vessel- takayasu, giant cell (inc. HLA-DR4 suggests antigen driven vascular inflammation)
-medium vessel- kawasaki, classic
-small vessel- Wegeners, microscopic, churg strauss
-very small- cryoglobulinemia, cutaneous, henoch-schonlein
-pathophys: immune complexes- platelet activating factor- inc. vascular permeability- inc. IC deposition, palpable purpura
-antigens; drugs, bugs, connective tissue disease, malignancy
-ANCA increases inflammatory vascular response
-cANCA- directed against antigen proteinase3 (PR3), assocaited with Wegeners, churg-strauss
-pANCA- directed against myeloperoxidase (MPO), associated with microscopic polyangiitis (MPA)
-AST and ALT are liver tests


Polymyositis and Dermatomyositis

-DM= CD4+, perivascular
-PM= CD8+
-characterized by muscle weakness
-skin rashes: gottrons papules, heliotrope, V sign, shawl sign, mechanics hands, periungual erythema
-anti-synthetase syndrome: PM or DM associated with: INTERSTICIAL LUNG DISEASE, fever, arthritis, mechanics hands
-antisynthetase antibodies: anti-jo (anti-*histadyl-tRNA synthetase), antiaminoacyl tRNA synthetases (CYTOPLASM), MARKERS of DISEASE (NOT PATHOLOGIC OR MYOTOXIC)
-evidence suggests viral etiology- no proof of virus though
-juvenile DM- inc. antibodies to coxsackie B
-seasonal- anti-jo-1 antibodies in spring
-ANA can be positive in this disease
-DM: creatinine kinase will be high