Cardiovascular pathology: blood vessels (degenerative changes, vasculitis) Markéta Hermanová nNormal arterial structure: -Intima (endothelium+connective tissue) -Media (elastic tissue; in medium sized arteries – smooth muscles) -Adventitia (fibrous connective tissue) - nAge related vascular changes: -Progressive fibrous thickening of the intima -Fibrosis ans scarring of the muscular or elastic media -Accumulation of mucopolysaccharide-rich ground substance -Fragmentation of the elastic laminae n n nArteriosclerosis: „hardening of the arteries“, arterial wall thickening and loss of elasticity n -Arteriolosclerosis (hyaline and hyperplastic; related to hypertension) - -Monckenberg medial sclerosis-mediocalcinosis (calcified deposits in muscular arteries in extremitites, older people) - -Atherosclerosis n Atherosclerosis nLarge and medium-sized arteris n nElevated lesions: fatty streaks, atherosclerotic (fibrous+atheromatous) plaques and complicated lesions (ulceration, thrombosis, calcification and bleeding) n nMajor cause of organ ischaemia (e. g. Myocardial infarction) n nRisk factors: age, male gender, genetics, hypertension, smoking and diabetes, some infections (CMV, chlamydia pn., influenza,…), metabolic syndrome. n n↑LDL, cholesterol, fibrinogen and fVII; ↓HDL n n n n Atherosclerosis _aorta-fatty-streaks-1-330c CV016 fatty streaks • atherosclerotic (fibrolipid) plaques AS – complicated lesions _ath-obliterating-330d _aorta-heavy-athero-330d obr01 obr03 obr06 CV120 •AS of coronary artery •AS fibrolipid plaque •Cholesterol crystals in AS plaque •Bleeding into AS plaque Pathogenesis of arteriosclerosis nEndothelial injury -mechanical denudation, hemodynamic forces, immune complex deposition, irradiation, chemicals,… -Endothelial dysfunction: increased permeability, enhanced leukocyte adhesion, altered gene expression (expression of cell adhesion molecules, increased thrombogenisity) nAccumulation of lipoproteins nCellular reaction in the focus of injury -monocyte adhesion to endothelium, migration into intima and transformation into macrophages and foamy cells -Platelet adhesion -Migration of smooth muscle cells from media into intima or smooth muscles recruitment from circulating precursors -Smooth muscle proliferation and production of proteins of ECM (collagen, elastin, proteoglycans) -Lipid accumulation (both extra- and intracellularly (in macrophages and smooth muscles) - n 3 - patogeneze aterosklerózy.emf 3 - patogeneze aterosklerózy.emf 3 - patogeneze aterosklerózy.emf 3 - patogeneze aterosklerózy.emf 3 - patogeneze aterosklerózy.emf Atherosclerosis - pathogenesis Atherosclerosis – cell interactions in an atheromatous plaque 4 - buněčné interakce při ateroskleróze.emf Morphology of atherosclerosis nFatty streaks n nAtherosclerotic plaque (fibrous and atheromatous) -cells (smooth muscle cells, inflammatory cells and macrophages,…) -ECM (collagen, elastic fibers, proteoglycans) -lipids (intra- and extracellular) n nComplications -Rupture, ulceration or erosion, thrombosis -Hemorrhage into a plaque -Atheroembolism -Aneurysm formation n n n n - n n Consequences of atherosclerosis nProgressive lumen narrowing; occlusion of smaller arteries n nAcute atherothrombotic occlusion n nEmbolisation of atheroscleroic debris causing distal vessel occlusion n nRupture of abdominal atherosclerotic aneurysm n nVasoconstriction n n n Clinical consequences nCerebral infarction nMyocardial infarction nPeripheral vascular disease with intermitent claudication nGangrene nAortic atherosclerotic aneurysm nCarotid atheroma embolisation Hypertension: increased systemic and local tissue blood pressure nEssential (primary) nSecondary hypertension n nBorderline hypertension: 140/90-160/95mmHg nMild hypertension: diastolic pressure 95-104mmHg nModerate hypertension: diastolic pressure 105-114mmHg nSevere hypertension: above 115 mmHg n nBenign (gradual organ damage) nMalignant (severe renal, retinal and cerebral damage) nPrimary (essential) hypertension (etiology unknown, multifactorial) -Genetic susceptibility -Excessive sympathetic nervous system activity -High salt intake -Abnormalities in renin-angiotensin-aldosteron system nSecondary hypertension -Renal diseases -Endocrine causes (adrenocortical hyperfunctions, pregnancy induced, thyreopathies, acromegaly,…) -Coarctation of aorta, PAN, increased intravascular volume, increased cardiac output, rigidity of aorta -Drugs (e. g. Contraceptives, corticosteroids,…) -Hormones producing tumors: renin producing tumors, pheochromocytoma,…… -Psychogenic causes, acute stress, increased intracranial volume,… - Pathological classification nBenign hypertension -Left ventricular hypertrophy – congestive heart failure – ventricular dilatation -Acceleration of atherosclerosis -Intimal proliferation and hyalinisation of the muscularis media in medium sized renal arteries and arterioles – benign nephrosclerosis - nMalignant hypertension -Diastolic blood pressure usually above 130mmHg -Progressive renal disease – renal failure (necrotising arteriolitis-fibrionoid necrosis of arterioles); accelerated hypertension -Cardiac failure -Papilloedemea and retinal haemorrhages -Severe headache and cerebral haemorrhage - n+ pulmonary hypertension - Diabetic vascular disease nPremature atherosclerosis nMicroangiopathies: damage of kidneys, nerves and retina (abnormal glycosylation of proteins within the vessel wall; thickening but with increased permeability; micro-albuminuria; micro-aneurysms; capillary thrombosis (retina); damage of vessels supplying nerves) -Diabetic retinopathy -Diabetic glomerulosclerosis -Peripheral neuropathy n nComlications: gangrene, renal failure, blindness Malignant nephrosclerosis – fibrinoid necrosis of arterioles – necrotising arteriolitis HE 100x Mallory 40x 2 Aneurysms: localised, permanent, abnormal dilatation of a blood vessel Localisation of aneurysms Clinical effects Atherosclerotic Lower abdominal aorta and iliac arteries Abdominal mass, lower limb ischaemia, rupture Aortic dissection Aorta and major branches (intramural bleeding) ↑BP, Marfan sy, cystic medionecrosis Loss of peripheral pulses, haemopericardium, rupture external or re-entry Berry Circle of Willis SAH Micro-aneurysms Intracerebral capillaries Intracerebral haemorrhage, as. hypertension Syphilitic Ascending and arch of the aorta Aortic incompetence Mycotic Root of aorta (from endocarditis) Any vessels Thrombosis or rupture, cerebral infarction or haemorrhage Aneurysms _aorta-abd-aneurysm-330e _aneurysm-circ-willis-331f •AS aneurysm – abdominal aorta •Berry aneurysm of circle of Willis disekce aorty •Aortic dissection Pathogenesis of vasculitis nInfectious -Bacterial -Rickettsial -Spirochetal (syphilis) -Fungal (aspergilosis, mucormycosis)→mycotic aneurysm, thrombosis, infarction -Viral (herpes zoster, varicella) n nImmunologic n nUnknown/(immunologic) -Giant cell (temporal) arteritis -Takayasu arteritis -Polyarteritis nodosa n Immune mediated vasculitis nImmune-complex-mediated -Infection-induced (hepatitis B and C virus) -Henoch-Schonlein purpura (IgA+C3, small vessels) -SLE and rheumatoid arthritis -Drug-induced -Cryoglobulinemia -Serum sickness (reaction to protein in antiserum derived from non-human sources) nAntineutrophil cytoplasmic antibody (ANCA)-mediated -Wegener granulomatosis -Microscopic polyangitis (microscopic polyarteritis) -Churg-Strauss syndrome nDirect antibody mediated -Good-Pasture syndrome (anti-GMB antibodies) -Kawasaki disease (anti-endothelial antibodies) nCell mediated -Organ allograft rejection nInflammatory bowel disease (ulcerative colitis, morbus Crohn) nParaneoplastic nLarge vessel vasculitis -Giant cell (temporal) arteritis n (granulomatous, extracranial branches of the carotid artery; +polymyalgia rheumatica) n -Takayasu arteritis n (granulomatous; aorta and major branches; pulsless disease) n nMedium-sized vessel vasculitis -Polyarteritis nodosa n (necrotizing, transmural; all stages coexist; in any organs with exception of the lung) n -Kawasaki disease=mucocutaneous lymph node syndrome n (PAN-like vasculitis; coronary arteries affected; children) n nSmall vessel vasculitis -Polyangiitis with granulomatosis/Wegener granulomatosis n (M>F; necrotizing granulomas of respiratory tract +necrotizing or n granulomatous vasculitis+focal necrotizing often crescenting n glomerulonephritis) n -Churg-Strauss syndrome n (allergic granulomatosis and angitis: necrotizing vasculitis+granulomas with n eosinophilic necrosis + allergic rhinitis, asthma bronchiale, eosinofilia) n -Microscopic polyangitis (polyarteritis), hypersensitivity, leukocytoclastic vasculitis n (necrotizing vasculitis, palpable purpura of the skin and mucous membranes +often necrotizing glomerulonephritis, pulmonary capillaritis; lesions of the same age) n nORL: - repeated respiratory tract inflammation n - exudate rich in plasma cells + eosinophils n nKidney: - glomerulonephritis n nLung: - variable presentation of lung diseases + hemoptysis n nSkin: - ulceration, necrosis, petechiae-purpura n nGIT: - ischemic ulcerations (sharply demarcated, without HP, minimal inflammation) n n Possible clinical signs of systemic vasculitis n fever, nausea, myalgia, arthralgia n skin purpura n signs of nephritis n abdominal pain n n n ngeneral malaise (~ severe influenza, long duration, resistant to usual therapy) n sinusoid course (relapse --- remission --- relapse--) n Patient presentation D:\SCContent\9781416031215\graphics\fullsize\S9781416031215-011-f022.jpg •ANCA •PAN •Kawasaki •Giant-cell a., Takayasu •Microscop. polyangiits •Wegener •Churg-Strauss. sy Polyarteritis nodosa 01194+ 01195+ Polyarteritis nodosa 01527+ Thrombangiitis obliterans (Buerger disease) nSegmental, thrombosing, acute and chronic inflammation of medium-sized and small arteries n nTibial and radial arteries (extension to veins and nerves of extremities)- all structures encased in fibrous tissue n nCigarette smoking (hypersenzitivity to intradermally injected tabacco extracts) n nHLA-A9 and HLA-B5 n Raynaud Phenomenon nParoxysmal pallor or cyanosis of the digits o the hands and feet; less frequently acral parts (nose, ears) nCold induced vasoconstriction of the digital arteries, precapillary arterioles, cutaneous A-V shunts nStructural changes of the arterial wall absent; late in the course intimal thickening nLate in the course: atrophy of the skin, subcutaneous tissues and muscles, ulcerations, ischemic gangrene n nPrimary, usually uncomplicated nSecondary (in SLE, scleroderma, atherosclerosis, Buerger disease), more severe n n Venous thrombosis nImmobility (post-operative phase, cardiac failure, bed rest, fractures, long flights…) n nCancer (thromophlebitis migrans: superficial venous thrombi) n nPregnancy and childbirth n nOestrogen therapy (contraceptives, hormonal treatment of prostatic cancer,…) n nHaematological disorders (polycythaemia, factor V Leiden (mutated) and antithrombin III deficiency,…) n Thrombophlebitis and phlebothrombosis nDeep venous thrombosis in deep leg veins: 90 % cases of thrombophlebitis and phlebothrombosis n+ periprostatic venous plexus, pelvic venous plexus, large veins in skull and the dural sinuses nPulmonary embolism!!!! n n nIn setting of infection and inflammation n n n nVaricose veins of superficial veins of the upper and lower leg n- Dilated, tortuous veins -Increases intraluminal pressure and loss of vessel wall support -Superficial veins of the upper and lower leg -Familial tendency, pregnancy -Dilatation, stasis, congestion, oedema, pain, thrombosis, stasis dermatitis, varicose ulcers n nOther varicosities -Esophageal varices (in liver cirrhosis – in portal vein hypertension; the opening of porto-systemic shunts) -Hemorrhoids (primary varicose dilatation of the venous plexus at the anorectal junction) n nSuperior and inferion vena caval syndromes -Neoplasms that compress the superior or inferior vena cava n Vascular tumors and tumor-like conditions nBenign tumors nVascular tumors of intermediate malignancy nMalignant vascular tumors Benign tumors and tumor-like lesions nHemangioma -Capillary -Cavernous -Pyogenic granuloma (lobular capillary hemangioma) nLymphangioma -Capillary -Cavernous nVascular ectasias -Nevus flammeus -Spider teleangiectasia -Hereditary hemorrhagic teleangiectasia (Osler-Weber-Rendu disease) nReactive vascular proliferations -bacillary angiomatosis (opportunic infection of immunocompromised patients; G- Bartonella henselae, B quintana,…) -intravasculary papillary endothelial hyperplasia,… n Capillary hemangioma 1 •1 - capillaries •2 - endothelium •3 – red blood cells 2 3 Cavernous hemangioma kavernózní ham •1 septa •2 vascular spaces 2 2 1 nVascular tumor of intermediate malignancy nKaposi sarcoma nHemangioendothelioma n n nMalignant neoplasms nAngiosarcoma nHemangiopericytoma n Kaposi sarcoma n classic form – chronic, in mediterranean or n jewish origin, usually (90%) confined to skin n n endemic – south-african children, n lymphadenopatic, aggressive n n immunosuppression (transplant) associated – internal organs n in 50% n n AIDS associated Kaposi sarcoma n HHV-8, hyperproliferation of endothelial cells, prevention of apoptosis n n gross: red to purple patches – raised plaques – nodules n n micro: irregular blood spaces, plump atypical endothelial cells, + perivascular aggregates of spindle cells Kaposi sarcoma - • 11 - Kaposi makro Endomyocardial biopsy nPerformed during catetrization procedure n (right internal jugular vein, femoral vein – right ventricular EMB; n femoral artery – left ventricular EMB) nUnder fluoroscopic guidance nRisk of EMB: -Perforation with pericardial tamponade -Arrhythmias -Heart block -Pneumothorax -Puncture of central artheries -Venous hematoma -Pulmonary embolization -Nerve paresis -Vasovagal reaction -Damage to the tricuspid valve -Bleeding from the biopsy site -Deep venous thrombosis nto evaluate heart transplant recipients for rejection n(cellular rejection, vascular rejection) n nIn suspected: nCardiac amyloidosis, (glycogen, lysosomal storage disease,…) nMyocarditis nCardiomyopathy (alcoholic, idiopathic, hypertrophic, ischemic, peripartum, restrictive,…) nCardiac tumors n n>1 region of the right heart septum nNumber of samples (5-10), 1-2 mm3 nFixation in 10% neutral buffered formalin, light microscopy nFixation in 4% glutaraldehyde, transmission electron microscopy nFrozen samples for molecular studies n n n Classification of types of restrictive cardiomyopathy according to cause nMyocardial -Noninfiltrative nIdiopathic cardiomyopathy nFamilial cardiomyopathy nHypertrophic cardiomyopathy nScleroderma nPseudoxynthoma elasticum nDiabetic cardiomyopathy -Infiltrative nAmyloidosis nSarcoidosis nGaucher´s disease (lysosomal storage disease) nHurler´s disease (lysosomal storage disease) nFatty infiltration -Storage diseases nHemochromatosis nFabry´s disease (sfingolipidosis; ↓α-galactosidase) nGlycogen storage disease nEndomyocardial nEndomyocardial fibrosis nHypereosinophilic syndrome nCarcinoid heart disease nMetastatic cancers nRadiation nToxic effect of anthracyclin nDrugs causing fibrous endocarditis (serotonin, methysergide, ergotamine, mercurail agents, busulfan) n n Thank you for your attention …