j0305257 j0305257 Systemic Pathology CARDIOVASCULAR system j0305257 ATHEROSCLEROSIS •disease of large and medium-sizes arteries with lipid deposition into intima •active inflammatory process • •endogennous risk factors, mostly noninfluenceables : –age, MxF (estrogen?), familiar factors (f. hypercholesterolemia), hereditary homocysteinemia ð •exogennous risk factors: –hyperlipidemia (LDL) ←← hypothyreosis, nephrotic sy; –hypertension, diabetes mellitus, life style smoking (nicotine, CO), sedentary life, food + obesity; ↑CRP j0305257 Atherosclerosis - pathogenesis 1.Endothelial injury ð - mechanic (↑BP, turbulence) ð - endotoxins, immune complexes, exogennous toxins (cig. smoke), ↑ cholesterol ð ↑ expression of cell adhesion molecules, ↑ permeability, ↑ thrombogenicity ← 2.Lipoprotein insudation (LDL) – oxidation in intima 3. 3.Inflammation ð - blood monocytes (→foam cells), T-cells, platelets, smooth muscle cells → 4.Repair - proliferation of myointimal cells ð - synthesis of collagen, elastin, proteoglycans → fibrotic plaque, + lipid accumulation - atheromatous plaque ð ð stable plaque under repeated inflammation turns into unstable plaque – fibrous cap + endothelium rupture - thrombus j0305257 3 - patogeneze aterosklerózy.emf 3 - patogeneze aterosklerózy.emf 3 - patogeneze aterosklerózy.emf 3 - patogeneze aterosklerózy.emf 3 - patogeneze aterosklerózy.emf Atherosclerosis - pathogenesis j0305257 atherosclerosis – cell interactions in an atheromatous plaque 4 - buněčné interakce při ateroskleróze.emf j0305257 Atherosclerosis ûfatty streak ûfibrotic plaque ûatheromatous plaque ûcomplicated atheromatous plaque (ulceration, calcification, thrombosis) û j0305257 Atherosclerosis ûSEQUELS: arterial occlusion in situ û chronic (→ hypoxia, atrophy) û acute (→ ischemia, infarction, encephalomalatia) û embolism (thrombus, plaque material) û weakening of arterial wall (aneurysm), risk of rupture û bleeding (from plaque, fissured wall) û calcification (hypertensive factor) û j0305257 Atherosclerosis– fatty streak CV016 _aorta-fatty-streaks-1-330c j0305257 _ath-obliterating-330d Atherosclerosis – fibrous and atheromatous plaques j0305257 _aorta-heavy-athero-330d Atherosclerosis– plaque ulceration, mural thrombosis j0305257 obr01 1 lumen narrowing 2 intimal atheromatous plaque 3 undamaged wall 4 epicardial fat tissue 1 2 3 4 Atherosclerosis– coronary artery j0305257 obr03 1 fibrous plaque in intima 2 vessel lumen 3 media 4 adventitia 2 1 3 4 1 Atherosclerosis – fibrous plaque j0305257 obr02 1 atheromatous plaque in intima 2 vessel lumen 3 media 4 adventitia 5 intimal neovascularization 2 1 3 1 4 5 Atherosclerosis – atheromatous plaque j0305257 obr06 1 vessel lumen 2 media 3 vascularization 4 cholesterol crystals 3 1 4 4 2 Atherosclerosis – atheromatous plaque, intimal neovascularization j0305257 obr07 1 nuclei of foam cells 2 lipids in cytoplasm 1 2 2 Atherosclerosis – foam cells in atheromatous plaque j0305257 C:\Documents and Settings\Patol\Dokumenty\Haškovcová\patologie myokardu\c-1.jpg 1 abdominální aorta 2 trombóza a. mesenterica 3 truncus coeliacus 1 Atherosclerosis – complications thrombosis/thrombembolia 2 3 GI031 4 trombóza koronární a. 4 C:\Documents and Settings\Patol\Dokumenty\Haškovcová\patologie myokardu\d-1.jpg j0305257 _aorta-abd-aneurysm-330e _aneurysm-circ-willis-331f 3 a. cerebri anterior 4 a. cerebri media 5 a. cerebri posterior 6 a. basilaris 7 aneurysm 1 abdominal aorta 2 aneurysm Atherosclerosis – complications– aneurysm 1 2 3 4 5 6 7 j0305257 Arteriosclerosis ûin muscular arteries ûsmooth muscle hypertrophy ûintimal fibrosis ûcollagenisation of elastic membrane ûhyalinisation (hyaline a.) û ûage and/or hypertension related changes û→ nephrosclerosis, cerebral ischemia, … j0305257 Hyaline arteriolosclerosis Image028 j0305257 j0305257 Cardiac pathology j0305257 Morphology ûpericardial sac – cca 30ml clear yellowish fluid û û male = 300 – 350 g, ð - hypertrophy > 400g û û myocardium: û è RV 3 – 4 mm û è LV 12 – 15 mm û û foramen ovale ð - closed x opened è paradoxical embolia è srdce6 j0305257 Congenital cardiovascular disease j0305257 Pathological shunts ûatrial septal defect ûventricular septal defect ûpatent ductus arteriosus ûInitially left-to right shunts, i.e. non-cyanotic, later (in heart defects) right ventricular hypertrophy – reverse shunt, cyanotic defect j0305257 Ventricular septal defect j0305257 Ventricular septal defect j0305257 Atrial septal defect j0305257 Congenital stenosis ûcoarctation of the aorta – congenital constriction ûvalvular stenosis û ûHypertrophy, hypertension and dilatation ahead of stenotic part. Collateral circulation, if posssible. j0305257 Coarctation of the aorta ûAortic constricton ûwith patent dct. arteriosus (pre- or postductal) ûwith closed dct. arteriosus û ûCongestive heart failure, ûbacterial endocarditis, intracerebral haemorrhage û û j0305257 Complex congenital heart disease ûFallot‘s tetralogy ûtransposition of the great arteries û ûCombination of malformations, i. e. hypoplasia, shunting or incorrect connection, stenosis, etc. j0305257 Fallot‘s tetralogy ventricular septal defect with dilatated overriding aorta, stenosis of the pulmonary valve, right ventricular hypertrophy j0305257 1) û 1) Pericardial effusion û - transudate in congestive heart failura or hypoproteinemia, slow (up to 500ml – pericardial dilatation) û û û 2) haemopericardium û – wall rupturein MI or aortic root dissection è fatal cardiac tamponade û û û diastolic filling restriction • Pericardial pathology j0305257 Pericardial pathology û 3) Inflammatory exudate in pericarditis: û ða) non-infectious û – pericarditis epistenocardiaca, uremic, post-operative, SLE, Dressler sy (post-MI autoimmune) û û b) infectious ð – haematogenous, direct spread, lymphogennous; variable agents û û û j0305257 Acute fibrinous pericarditis ûGross: yellow-greyish superficial coating – granular layer, villi - cor villosum, hirsutum; ûMicro: mesh of thin eosinophilic strands, commonly + inflammatory infiltrate ûHealing: may be complicated. Fibrinolysis x organisation by granulation tisssue → adhesions, dystrophic calcification. û j0305257 Acute fibrinous pericarditis Peric j0305257 fibrinous pericarditis fibrińozní perikarditis 20x.jpg fibrińozní perikarditis 100x.jpg 1 1 1 1 fibrinous exudate j0305257 Systemic hypertension ûPrimary (essential) h. ûSecondary h. (renal, endocrine hyperfunction, aortic coarctation, drug induced) j0305257 Systemic hypertension and heart û90–95% essential , risk factor for AS û ûwork overload è LV adaptation to peripheral resistance = cor hypertonicum (concentric LV hypertrophy) è limited compensatory mechanisms è cor hypertonicum decompensatum (dilatation of hypertrophic LV) û ûè heart insufficiency á relative coronary incompetence hypertrofie myokardu LKS j0305257 Cor hypertonicum Image032 j0305257 LV hypertrophy LV hypertrophy j0305257 Heart failure û heart unable to pump blood at a rate sufficient for metabolic demands of the tissues û û systolic dysfunction - ↓ myocardial contractile function (ischemic injury, pressure or volume overload – valvular disease, hypertension, cardiomyopathy û diastolic dysfunction - inability to dilatate sufficiently (massive LV hypertrophy, myofibrosis, amyloidosis) û û cardial – extracardial pathologic changes j0305257 Cardial changes û ûdisproportion between heart function and peripheral vascular resistance û û differ according rapidity of development: û – sudden è acute dilatation û û – chronic è adaptation è è è û myocardial hypertrophy ( nutritional demands) +/- ventricular dilatation (enhanced contractility – Frank-Starling mechanism), + activation of neurohumoral systems (norepinephrin, renin-angiotensin sy, atrial natriuretic peptide û j0305257 Extracardial changes ûvenoous congestion – e.g. liver (-> hepar moschatum) û ûinduration – fibroproduction (liver, spleen, kidney) û ûoedema – û ûcyanosis – visible on acral parts j0305257 Chronic venous congestion (nutmeg liver - hepar moschatum) j0305257 Hepatic venous congestion městnání v játrech 20x 1 2 2 1 1 1 Portal spaces 2 Congestive lines (severe congestion with hepatocyte necrosis) --- pseudolobule: confluent remnants of 3 lobules, centrally portal space j0305257 Pulmonary oedema edem plic 100x 1 oedematic fluid 2 widening of septa 3 capillary dilatation 1 1 2 3 j0305257 chron venostáza plíce Chronic pulmonary venous congestion 1 1 1 oedematic fluid è hyperemic septa Æ siderophages j0305257 Ischemic heart disease (IHD) ûgroup of pathophysiologically related syndromes resulting from myocardial ischemia (hypoxia or anoxia, ↓ nutrients, ↓ removal of metabolites) û ûimbalance between the demand and supply by coronary arteries. û û important factor – coronary AS û û forms: ðangina pectoris ðmyocardial infarction (MI) ð chronic IHD with heart failure ð sudden cardiac death j0305257 Ischemic heart disease (IHD) ûMorphology of myocardial ischemia: ð myofibrosis ð myomalatia (= partial necrosis – cardiomyocytes only) ð myocardial infarction: transmural/subendocardial (complete coagulative necrosis incl. interstitium) û j0305257 obr14 1 cardiomyocytes 2 myofibrosis 3 vessels 1 Myofibrosis 2 3 j0305257 obr10 1 myomalatia 2 normal cardiomyocytes 3 myofibrosis 1 1 2 3 Myomalatia j0305257 Pathogenesis of IHD 1)AS of coronary aa. û – commonly at a. branching û – fixed obstruction by plaque (fibrous, atheromatic) û – acute plaque change (rupture, erosion, haemorrhage, thrombosis) û – 75% stenosis – ischemia during á workload – stable angina pectoris û – 90% stenosis –ischemia even at rest – ustable angina - preinfarction û û2) non-atherosclerotic û – coronary emboli – endocarditis, atrial fibrillation, mural thr., paradoxical e. û – coronary vasospasm û – aortic dissection û – coronary vasculitis û – congenital coronary aa. defects û –hematologic disorders, amyloidosis, shock, etc. û û û j0305257 Angina pectoris (AP) û transient myocardial ischemia è chest pain !!! - û1. stable (typical) û – due to increased workload, duration ≤ 15 min, relieved by rest or nitroglycerin û – no myocardial necrosis û –subendocardial LV myocardium û û2. unstable û – increasing frequency / duration of pain attack, even at rest û – plaque disruption + mural thrombosis, possible vasospasm û – preinfarction angina û û3. variant (Prinzmetal) angina û – mostly unrelated to physical activity, coronary vasospasm - vasodilatative therapy û û û j0305257 Myocardial infarction ûischaemic coagulative necrosis ûCauses: usually coronary thrombosis, complicated atheromatic plaque, event. embolism, spasm, inflammation. Rarely systemic causes. ûGross: evolution; first signs (red, softer) after 12 hrs., 2-3 days established infarction (yellowish, haemorrhagic rim), weeks – formation of firm white fibrotic scar ûMicro: necrotic cells more red, loss of nuclei and striation. Neutrofils, later macrophages in stroma, reparation by granulation tissue, scar û j0305257 _myoc-fresh-ihf-322a 1 subendocardial coagulative necrosis 2 hyperemic rim 3 normal myocardium 4 epicardium 2 Myocardial infarction 1 1 2 4 3 j0305257 Myocardial infarction ûMicro: û12-24 hr: edema, hypereosinophilia of necrotic cells, pyknosis û1-3 days: neutrophils, loss of nuclei û3-7 days: macrophages at the border, desintegration of myofibers û1-2 wk: repair by granulation tissue, û cca 2 mo: scar û j0305257 1 3 2 5 4 1 coagulative necrosis 2 myomalatia 3 hyperemic rim 4 neutrophils 5 regressive changes Microscopic changes in developed MI j0305257 Myocardial infarction ûtransmural (QIM, STEMI) - + ST elevation on ECG û – ≥ ¾ of wall thickness, breadth >25 mm û – complete coronary artery obstruction û emergency angioplasty/stenting û û non-transmural (subendocardial, Non-STEMI) û – internal ¼ až ½ of LV wall û – collateral bllod flow, incomplete obstruction, shorter ischemia j0305257 MI complications 1.sudden death (arrythmia) 2.cardiogenic shock (contractile dysfunction) 3.pericarditis epistenocardiaca ð -> sero-fibrinous inflammation 4.mural thrombosis ð -> embolism into systemic circulation (-> brain, kidney, intestine, spleen infarction) 5.ventricular aneurysm ð -> acute – risk of rupture, trhrombosis; chronic – LV insufficiency 6.cardiac rupture ð -> free wall, septum, : tamponade / acute heart failure 7.papillary muscle rupture ð -> valvular incompetence → acute heart failure j0305257 MI complications û persistent pain – extension of infarct û Dressler‘s syndrome – autoimmune; chest pain, fever, effusion during weeks – months û progressive late heart failure - IHD û j0305257 _heart-infarct+thrombus MI – mural thrombosis j0305257 _heart-ruptured-wall-inf Mi – rupture j0305257 _cardiac-tamponade-2-66e _cardiac-tamponade-1-66e 1 lung 2 pericardial sac 3 blood coagulum 4 thoracic wall 3 1 2 1 1 4 4 MI – rupture, tamponade j0305257 CV143 1 aneurysm w. thrombosis 2 RV 3 LV 4 mitral valve 4 1 2 3 MI – LV aneurysm j0305257 Chronic ischemic heart disease (IHD) ûangina pectoris or MI in anamnesis û ûprogressive heart failure due to ischemic myocardial damage è LV failure è congestive RV failure û ûheart hypertrophy + dilatattion, myofibrosis and/or post-MI scars û ûmultiple coronary arteries with significant AS stenosis û ûimminent risk of MI, sudden cardiac death due to arrythmia, heart failure j0305257 Sudden cardiac death û= unexpected death from cardiac causes, without preexisting symptoms or within 1 hr of the onset of symptoms û ûmost commonly due to lethal arrythmia (ventricular fibrillation, asystole) û ûsudden collapse without signs of acute MI û ûother causes: ðdissecting/ruptured aortic aneurysm ðpulmonaty thrombembolism ðmassive intracerebral haemorrhage ðheritable conditions incl. anatomic, electriical – channelopathies ð ð û û j0305257 Myocarditis ûmyokardial inflammatory damage without ischemia û ûgross: ð cardiac dilatation, flabby, mottled myocardium û û micro: ðinflammatory infiltrate (acccording etiology) + cardiomyocyte regressive changes incl. necrosis û û etiology: ð viruses, ricketsia, chlamydia, bacteria (diphtheria, sepsis), fungi, protozoa (toxoplasmosis), helminths (trichinosis) ð immune-mediated (drug hypersesitivity, postviral, rheumatic fever, rejection) ðionising radiation ðunknown (giant-cell myocarditis j0305257 Viral myocarditis û Coxsackie, parvovirus B19, influenza, EBV, CMV, HIV û ûinflammatory infiltrate: T-cells mostly û û after acute attack commonly autoimune-mediated cardiomyocytes destruction û and fibrosis → dilated cardiomyopathy û û j0305257 Viral myocarditis û myokarditida 100x.jpg myokarditida 40x.jpg 1 cardiomyocytes 2 lymphocytic infiltrate in interstitium 2 2 2 1 1 j0305257 myokarditida 400x.jpg Viral myocarditis 1 cardiomyocytes 2 lymphocytic infiltrate in interstitium 1 1 2 2 j0305257 Septic myocarditis CV053 1 cardiomyocytes 2 bacterial colony 3 neutrophils 1 2 3 1 1 3 3 j0305257 Cardiomyopathies û= heart disease due to myocardial abnormality, with heart dysfunction ûdiagnosis after exclusion of IHD, valvular disease, congenital d. or hypertension û ûheterogenous group of disorders: ð dilated (DCM) •– dilatation + hypertrophy,¯ LV contraction, possible mural thrombosis; 20–50% genetic (AD); alkoholic, peripartum, myocarditis... ð hypertrophic (HCM) •– massive LV hypertrophy, 100% genetic, diastolic dysfunction, histologic „disarray“ ð restrictive cardiomyopathy • – diastolic dysfunction, ¯ of compliance - ¯ filling, myocardial stiffness ð specific CM •– Duchenne muscle dystrophy, toxic (drugs), endocrine d., metabolic d. (hemochromatosis, amyloidosis, glykogenosis,…) û û j0305257 Myocardial amyloidosis ûlocal x systemic (mostly AL amyloidosis) û ûsenile amyloidosis ðatrial + ventricles; amyloid protein = prealbumin (transthyretin) û ûisolated atrial amyloidosis ð amyloid protein = atrial natriuretic peptide û ûgross: consistency normal - firm (rubbery) û ûmicro: variable amyloid deposits v interstitium and vessels, Congo red + polarization û û j0305257 Myocardial amyloidosis j0305257 Myocardial amyloidosis j0305257 Endocardial / valvular diseases û ûendocarditis ðinfectious or immune-mediated endocardial inflammation ð ûdegenerative diseases ðcalcific aortic (rarely mitral) stenosis, mitral valve prolapse, annular and marginal sclerosis ð ûendocrine diseases ðcarcinoid syndrome û ûnonbacterial thrombotic endocarditis (in debilitated patients) û j0305257 Mitral valve prolapse mi-prolaps j0305257 Aortic valve calcification j0305257 Rheumatic fever, rheumatic heart disease ûacute non-purulent, imunne-mediated systemic poststreptococcall inflammation (cross-reactive antibodies) û ûacute stage: PANCARDITIS ðfibrinous pericarditis + myocarditis with Aschoff bodies (foci of fibrinoid necrosis + inflammatory reaction + verrucous endocarditis (small depositions of fibrin along the closure lines of Ao a Mi valves) ð ðacute endocarditis commonly recurrent ð ûchronic stage: ð diffuse fiubrous thickening + distortion, commisural fusion → dystrophic calcifikacation - stenosis + incompetence) ð û j0305257 7 - revmatické postižení srdce.emf rheumatic heart disease Verrucous endocarditis Aschoff body 7 - revmatické postižení srdce.emf Commisural fusion j0305257 Infective endocarditis û ûcommonly by highly virulent microorganisms ðStrep. pyogenenes, Strep. pneumoniae, Staph. aureus, … ev. fungi ð ûsubacute IE – less virulent microorganisms ðviridans streptococci ûpredisposition: ðdeformed valve, bioprosthesis, postcatethrization, i.v. drug addicts û û ûbacteremia - endocardial damage by bacteria - trombosis = infective vegetation û ð j0305257 Infective endocarditis ûgross: friable red-brown mass 0,5-2 cm on leaflets or chordae tendinae, valvular damage incl. ulceration û û ûmicro: ð fibrin + bacterial colonies + neutrophils (+ granulation tissue) ð Inflammation/ necrosis of the valve tissue ð ð ûcomplications: ð acute: valvular damage, myocarditis + abscess, pyemia,thrombembolism ð chronic valvular disease û j0305257 _heart-endocarditis-bacterial-valve-destruction 1 vegetation 2 endocardium 3 papillary muscle 4 myocardium Infective endocarditis– valve destruction 1 2 3 4 j0305257 Infective endocarditis 9 - IE.emf Mi vegetations Ao valve destruction purulent inflammation IE repair (Mi fenestration without vegetations) j0305257 obr20 1 bacterial colonies 2 trombus 3 red + white blood cells 1 3 Infective endocarditis - vegetations 1 1 2 j0305257 Infective endocarditis - vegetations endocarditis 100x.jpg 1 1 2 2 3 3 1 bacterial colonies 2 trombus 3 inflammatory infiltrate j0305257 Non-bacterial thrombotic endocarditis ûsterile vegetations due to hypercoagulative state Þ concurrent venous thrombosis and lung embolization û ûin generalized malignancies, chronic nephropathy with uremia, COPD etc. û ûmostly on mitral valve (normal) û ûmicro: verrucous vegetations (single or multiple), 1-5 mm, bland thrombi û û ûpossible source of emboli j0305257 _endocarditis-nonbacterial-thrombotic 1 mi valve 2 endocardium 3 papillary muscle 4 trombi 5 myocardium 2 1 3 4 4 4 5 Non-bacterial thrombotic endocarditis j0305257 Carcinoid syndrome endocardial fibrous plaquelike thockenings – RA, RV j0305257 j0305257 Cardiovascular tumors j0305257 Capilary hemangioma 1 1 - capillaries 2 - endothelium 3 – red blood cells 2 3 j0305257 Cavernous hemangioma ûgross: ðred -blue focus (nodular) ðpossible large size (-15 cm) ð liver, spleen, skin; commonly multiple ûmicro: ðlarge blood-filled vascular spaces divided by fibrous septa j0305257 Cavernous hemangioma kavernózní ham 1 septa 2 vascular spaces 2 2 1 j0305257 Kaposi sarcoma ûclassic form – chronic, in mediterranean or jewish origin, usually (90%) confined to skin ûendemic – south-african children, lymphadenopatic, aggressive ûimmunosuppression (transplant) associated – internal organs in 50% ûAIDS associated j0305257 Kaposi sarcoma ûHHV-8, hyperproliferation of endothelial cells, prevention of apoptosis ûgross: red to purple patches – raised plaques – nodules ûmicro: irregular blood spaces, plump atypical endothelial cells, + perivascular aggregates of spindle cells j0305257 Kaposi sarcoma - 11 - Kaposi makro j0305257 Image028 Kaposi sarcoma j0305257 Kaposi sarcoma 12 - Kaposi, HE fusicellular proliferation, hyaline globules, hemosiderin j0305257 ûprimary tumors rare, mostly benign myxomas û û ûmalignant mesenchymal (sarcomas) ðleiomyo - , rhabdomyo - , hemangio - , fibrosarcoma û û ûsecondary tumors ð20-30 x more common than primary ðmetastases + infiltrates : lung, breast carcinomas, malignant melanoma, malignant lymphomas and leukemias ð direct spread (lung ca, mesothelioma, renal ca) ðpericarditis carcinomatosa – hemorrhagic effusion û Heart tumors j0305257 Benign tumors ûMyxoma ð mostly in the left atrium (fossa ovalis on septum) ð4 – 6 cm, usually single ð sessile x pedunculated, papillary x villous, soft – gelatinous, regressive changes (haemorrhage, fibrosis) ð •micro: polygonal (stellate / globular) cells in myxoid matrix (acid mucopolysaccharides) ûother: hemangioma, lipoma, rhabdomyoma… j0305257 14 - myxom srdce LV myxoma j0305257 Myxoma (100x) myxom 100x.jpg 1 stellate cells 2 myxoid matrix 3 hemosiderin deposits Textové pole: 1 1 1 2 2 3 j0305257 Myxoma (400x) myxom 200x.jpg 1 stellate cells 2 myxoid matrix 1 1 2 2 j0305257 Angiosarcoma 13 - angiosarkom CD31 RV angiosarcoma j0305257 Angiosarcoma 1- mitoses 1 1 j0305257 ûtear in aortic intima - intramural bleeding through media, false lumen, possible „double-barreled“ aorta û ûtypic in ascending aort, 1–8 cm above aortic valve û ûante– and retrograde spread to the aortic root û ûcommon thrombosis in false lumen û ûrisk of external rupture (è hemoperikardium), progression at the aortic branches (èvariable organ‘s ischemia), heart failure û ûpredisposition – hypertension, Marfan sy, cystic medial necrosis, … Aortic dissection j0305257 typy disekcí Aortic dissection j0305257 disekce aorty Aortic dissection j0305257 VASCULITIS ûVessel wall inflammation û ûClassification according cause: infectious x non-infectious (commonly immune-mediated, ANCA+/ANCA-) û ûType (size) of vessel involved: Large-vessel û Medium-vessel û Small-vessel j0305257 Vasculitis ûANCA+ vasculitis (dangerous, even fatal within a few years, if not recognised) ðWegener granulomatosis ðChurg-Strauss syndrome ðmicroscopic polyangiitis ð ûANCA- vaskulitis: ðpolyarteritis nodosa ðKawasaki disease ðgiant-cell arteritis (Horton, temporal)) ðTakayasu arteritis ðthrombangiitis obliterans (Bürger disease) ðleukocytoclastic (alergic) vasculitis – cca 30% ð j0305257 ûORL: - repeated respiratory tract inflammation û - exudate rich in plasma cells + eosinophils û ûKidney: - glomerulonephritis û ûLung: - variable presentation of lung diseases + hemoptysis û ûSkin: - ulceration, necrosis, petechiae-purpura û ûGIT: - ischemic ulcerations (sharply demarcated, without HP, minimal inflammation) û ûChronic debilitating disease – clinical signs of tumor!! û Possible clinical signs of systemic vasculitis j0305257 • fever, nausea, myalgia, arthralgia • skin purpura • signs of nephritis • abdominal pain • • • •general malaise (~ severe influenza, long duration, resistant to usual therapy) • sinusoid course (relapse --- remission --- relapse--) • Patient presentation j0305257 û ûautoimmune process û ûinfection ðie. streptococcus, … ðdirect cause of infective v., or trigger factor of pathological immune processes Etiology j0305257 D:\SCContent\9781416031215\graphics\fullsize\S9781416031215-011-f022.jpg ANCA PAN Kawasaki Giant-cell a., Takayasu Microskop. polyangiits Wegener Churg-Strauss. sy j0305257 ûincidence ???? ð ≤20/1mil. inhabitants ðage 65+ - 53/1mil. inhabitants ð û ûprognosis: ð untreated ANCA+ vasculitis ≥80% fatal in 2 yrs ð treated ANCA+ vasculitis : ≥80% survives 5 yrs ð renal failure in elders >70 yrs - in 40% due to ANCA+ vasculitis ANCA+ vasculitis j0305257 Wegener granulomatosis ûPersistent pneumonitis (95%) – nodular infiltrates ûChronic sinusitis (90%) – ulcerations, event. destructive ûRenal disease (80%) – glomerulonephritis ûOther features: rashes, muscle pains, articular involvement, mono-/polyneuritis û j0305257 D:\SCContent\9781416031215\graphics\fullsize\S9781416031215-011-f026.jpg D:\SCContent\9781416031215\graphics\fullsize\S9781416031215-011-f026.jpg Small vessel vasculitis with giant-cell granulomatous reaction j0305257 ûANCA in approx. 70% (remaining by immunecomplexes or antibodies) û û= necrotizing vasculitis arterioles, capillaries, venules (synonyms: leukocytoclastic v., hypersensitive v., allergic v.) û û: SKIN, kidney, lung, GIT, brain… û ûhighly variable etiopathogenesis (part of systemic connective tissue diseases; alergic response to exogennous antigens – bacteria, viruses, drugs) û ûmicro: ðfibrinoid necrosis of vessel wall with neutrophils and chromatin fragments from neutrophil‘s nuclei - leukocytocllastic) ðall lesions in the same stage of evolution (X polyarteritis nodosa) ANCA+ VASCULITIS: microscopic polyangiitis j0305257 S01871-011-f026b nuclear fragments from neutrophils in a small vessel wall leukocytoclastic vasculitis j0305257 01194+ 1 thrombosed vessel lumen 2 fibrin deposition 3 mixed inflammatory infiltrate 1 2 polyarteritis nodosa 2 1 3 3 3 j0305257 01527+ 1 thrombosed vessel lumen 2 fibrin deposition 3 mixed inflammatory infiltrate polyarteritis nodosa 1 3 2 3 j0305257 2 3 Coronary aneurysms in a child‘ heart coronary artery with lamina elastica interna defects (arrows) and thrombotized aneurysms Kawasaki disease j0305257 S01871-011-f026e 4 Obliterative thrombosis with granuloma with central microabscess (arrow) acral necroses Thrombangiitis obliterans (Bürger disease) j0305257 Infectious vasculitis ûDirect invasion of vascular wall by inf. pathogen ûPrimary angioinvasive microorganism û Fungi: Aspergillus, Mucor - thrombosis→ ischemic necrosis ûLocalized vasculitis in focal infection û purulent – meningitis, pneumonia, abscess, fasciitis – pyogenic bacteria – secondary vasculitis û granulomatous, obliterative endarteritis – TB, tertiary syphilis, lepra û lymphocytic vasculitis – rickettsia (spotted fever, Q fever etc.), recurrent herpes, CMV û necrotizing vasculitis – anthrax û j0305257 Infectious vasculitis ûSepticemia in systemic infection û possible thrombosis, mycotic aneurysm, infected infarction û j0305257 Sec-vasc01