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1、自体免疫疾病自体免疫疾病器官特异性非器官特异性自体免疫疾病自体免疫疾病肌肉肾脏皮肤关节Pathological Factors in Rheumatic Disorders Rheumatic diseases are multisystem disorders caused by tissue damage resulting from autoantibodies,cytotoxic T lymphocytes,complement-fixing immune complex deposition,and inflammatory mediatorsInflammatory Paramet
2、ers1.1.ESRESR2.2.Acute phase reactantsAcute phase reactants3.3.ImmunoglobulinsImmunoglobulins4.4.Complement componentsComplement components5.5.Inflammatory mediators:cytokines,Inflammatory mediators:cytokines,prostanoidsprostanoids ESR are determined by the three forces Surface free energy(Van de Wa
3、als force):cohesive force Electrical charge associated with RBC:repulsive force Dielectric constant of the medium:dissipates the forceCalculation Equation for ESR Vs=2/9x(Ps-PL)R2/n x gVs=2/9x(Ps-PL)R2/n x gVs=the limiting velocity of the sphereVs=the limiting velocity of the sphereR=the radius of t
4、he sphereR=the radius of the spherePs and PL=the densities of the sphere and Ps and PL=the densities of the sphere and of the liquidof the liquidg=the acceleration due to gravityg=the acceleration due to gravityn=the viscosity of the liquidn=the viscosity of the liquidSerum Proteins and Drugs That A
5、ffect the ESR RateESR increaseESR decrease Fibrinogen ACTH Immunoglobulins Cortisone Dextran Ethambutol Methyldopa Quinine Procainamide Salicylate Oral contraceptives Penicillamine Methylsergide Theophylline Trifluperidol Vitamine AAcute Phase ReactantsThe Acute Phase Response Follows Cell Injury an
6、d The Acute Phase Response Follows Cell Injury and Tissue Damage Caused by:Tissue Damage Caused by:Acute infections:i.e.,bacterial or parasiticAcute infections:i.e.,bacterial or parasiticTrauma:i.e.,blunt,surgery,and burnsTrauma:i.e.,blunt,surgery,and burnsIschemic necrosis:i.e.,acute myocardial Isc
7、hemic necrosis:i.e.,acute myocardial infarctioninfarctionMalignant disease:I.e.,tumor growth and Malignant disease:I.e.,tumor growth and metastasismetastasisConnective tissue disease:i.e.,rheumatoid Connective tissue disease:i.e.,rheumatoid arthritis,rheumatic fever and othersarthritis,rheumatic fev
8、er and othersAcute abdominal inflammation:i.e.cholecystitis Acute abdominal inflammation:i.e.cholecystitis and pancreatitisand pancreatitisVaccination:I.e.,typhoidVaccination:I.e.,typhoidFunctional Properties of Human Acute Phase ProteinsFunctional GroupProteinFunctionHost defense proteinsC-reactive
9、 protein(CRP)Complement activation,opsonicationMannan-binding protein(MBP)Complement activation,opsonizationComplement proteins C3,C4,C5 Factor B,C9 Factor H,C4bpIncreased vascular permeability,opsonization,bacterial killingFibrinogenFormation of hemostatic plugs,wound healingProteinase inhibitors 1
10、-Proteinase inhibitor(1-PI)Control of extracellular matrix degradation 1-Antichymotrypsin(1-Achy)Control of extracellular matrix degradation 2-Antiplasmin(2-AP)Control of plasminC1 inhibitor(C1 INH)Control of complement and contace system activationAntioxidantsCeruloplaasminInhibition of oxy radical
11、 formationHemopexin(Hx)Binding of heme,inhibition of lipid peroxidationHaptoglobulin(HP)Binding of hemoglobulin,inhibition of lipid peroxidationFunction unknownSerum amyloid A(SAA)1-Acid glycoproteinC-Reactive Protein(CRP)Normal plasma protein,concentration from Normal plasma protein,concentration f
12、rom 0.068-8.8 mg/ml0.068-8.8 mg/mlAcute phase reactant,concentration up to Acute phase reactant,concentration up to 500mg/ml500mg/mlSynthesized by hepatocytesSynthesized by hepatocytesMolecular weight 105,500 daltonsMolecular weight 105,500 daltonsFive identical non-glycosylated,non-Five identical n
13、on-glycosylated,non-covalently associated subunitscovalently associated subunitsAmino acid sequence homologous with serum Amino acid sequence homologous with serum amyloid A component(SAA)amyloid A component(SAA)Rheumatic Disease in Which Elevated C-Reactive Protein Levels may OccurGoutRheumatoid ar
14、thritisJuvenile rheumatoid arthritisPsoriatic arthritisAnkylosing spondylitisReiters syndromePolymyalgia rheumatica-giant cell arteritisSystemic vasculitisWegeners granulomatosisBehcets syndromeSystemic lupus erythematosusc ACRc ACR类风湿性关节炎类风湿性关节炎(RA)(RA)类风湿性关节炎类风湿性关节炎(RA)(RA)1.类风湿性关节炎是一种重要的自体免疫疾病，可导
15、致关节破坏变形，骨骼变化以及全身性的病变。2.类风湿性关节炎的骨骼变化包括发炎关节旁的骨缺乏，软骨侵蚀。3.类风湿性关节炎是一种全身性的变化，患者不但关节疼痛，可能关节会逐渐变形。4.过去十年来，类风湿关节炎在冶疗上的改变有着明显的进步。我们不再视其为一仅局限于关节的慢性病变；反之，却视为一甚富侵略性的全身性疾患。Rheumatoid Arthritis(RA)Rheumatoid Arthritis(RA)A chronic,systemic,autoimmune,A chronic,systemic,autoimmune,inflammatory disease of unknown in
16、flammatory disease of unknown etiologyetiologyCharacterized by Characterized by persistent intense immunological persistent intense immunological activityactivityinflammatory and erosive inflammatory and erosive synovitis,usually involving synovitis,usually involving peripheral joint in a symmetric peripheral joint in a symmetric fashionfashionlocal destruction of bone and local destruction of bone and cartilagecartilagea variety of systemic a variety of systemic manifestation.manifestation.The
