病理生理学教学课件：05 Cardiovascular Diseases

1、Chapter VIDiseases of Cardiovascular System(心血管系统疾病)Cardio vascular systemHeart Blood vessels“Pump” More morbidity & mortality - Approximately half of all death caused by disorders of circulatory system - In US, myocardial infarction alone is responsible for 20-25% of all deathSystemic Pathology Eti

2、ology, Pathogenesis Pathologic morphology Clinico-pathological correlation ConsequenceGeneral pathology Systemic pathologyExample: Myocardial infarctionCoagulative necrosis Granulation tissueScarArrhythmiasmyocardial ruptureVentricular aneurysm Contractile dysfunction Heart failureshock, deathMorpho

3、logyConsequencesCardio vascular diseasesHeart Blood vesselsIschemic heart disease Atherosclerosis HypertensionRheumatic Heart DiseaseValvular heart disease (Infective Endocarditis) MyocarditisCardiomyopathy Large ( Elastic ): Aorta & large branches, pulmonary arteries Medial ( Muscular ): Coronary,

4、renal arteries Small ( = 1.0cm streaks, oil red staining (+) Ostia of branches - Fatty streak: foam cells - May evolve into advanced lesions or disappearMicroscopy2. Atherosclerotic plaque (粥样斑块)Gross: white to yellow, red-brown with thrombosis over the surface 0.3 1.5cm can coalesce to form larger

5、masses The basic structure of an atheromatous plaqueMicroscopy Masson trichrome stainF: fibrous capC: a central necrotic (lipid) coreL: lumenThe internal and external elastic membranes are destroyedThe media is thinned under the most advanced plaqueScattered inflammatory cells, calcification, and ne

6、ovascularization at the junction of the cap and coreNatural history, morphologic features & main pathogenic events Clinically important changes of atherosclerotic plaques Hemorrhage into a plaque Rupture, ulceration, or erosion thrombus formation Atheroembolism Calcification Aneurysm formationPlaque

7、 ruptureAcute coronary thrombosis on a plaque with focal rupture, triggering fatal myocardial infarctionHemorrhage into plaqueAneurysmAbdominal aortaAcute plaque change Three categories: Rupture/fissuring Erosion/ulceration Hemorrhage into the atheroma Clinical consequences of atherosclerosis Aorta

8、AneurysmCoronary A. Coronary Heart DiseaseCerebral A. Thrombosis, Aneurysm, Hemorrhage, Atrophy Renal A. Infarction, Nephrosclerosis, HypertensionFemoral, Popliteal, Tibial A. Intermittent cramp, GangreneIschemic Heart Disease (缺血性心脏病)(Coronary Artery Disease) Atherosclerosis Narrow or Occlusion of

9、Lumen of Coronary A. Coronary perfusion Myocardial demand Ischemia, Function Disturbance, Infarction of Heart Epidemiology Leading cause of morbidity and mortality in industrialized nations Annually, a half-million Americans die of IHD Cardiac risk factors: smoking cessation program hypertension & d

10、iabetic treatment cholesterol-lowering agents Normal heart “Pump” Weight: 250270g , 240260g Wall thickness: left ventricle 0.91.0cm right ventricle 0.30.4cm atrium 0.10.2cm Valves：a single direction of blood flow Myocardium ：nearly inexhaustible Blood supply: coronary arteriesCoronary arteries (冠状动脉

11、) Lesions of Coronary Atherosclerosis Plaque changes: thrombosis, hemorrhage, vasospasm Critical stenosis: = 75%The frequencies of occlusion of various coronary arteries and the distribution of the resultant infarctsLeft anterior descending coronary artery40%50%Anterior and apical left ventricle; an

12、terior two thirds of the interventricular septumRight coronary artery30%40%Posterior wall of the left ventricle; posterior one third of the interventricular septumLeft circumflex coronary artery 15%20% lateral wall of the left ventricleRupture, fissuring, or ulceration rapid thrombosisHemorrhage int

13、o the core of plaques Vasospasm Acute Plaque ChangeAcute coronary syndromes(急性冠脉综合征：chest pain, with nausea & sweating）Plaque ruptureAcute coronary thrombosis on a plaque with focal rupture, triggering fatal myocardial infarctionMassive plaque rupture with thrombus, triggering a fatal myocardial inf

14、arctionClinical Presentations 1. Angina pectoris 2. Myocardial infarction 3. Chronic coronary heart disease 4. Sudden coronary death Angina pectoris (心绞痛) An intermittent chest pain caused by transient, reversible myocardial ischemia (1) Stable - A fixed atherosclerotic narrowing (usually 70%) - Occ

15、ur in the setting of increased demands - Relieved by rest (reducing demand) or by administration of nitroglycerin (vasodilator) (2) Unstable - A fixed atherosclerotic narrowing (usually 90%) - Occur progressively at less levels of exertion or even at rest (3) Variant - Caused by vasospasm - Occur at

16、 restA crushing or squeezing substernal sensation, may radiate down the left armMyocardial Infarction (MI，心肌梗死) Necrosis of heart muscle resulting from ischemia Most MIs are caused by acute coronary artery thrombosis Plaque disruption Platelet aggregation & vasospasm Thrombosis Occluding the coronar

17、y artery lumen IschemiaMyocardial Response to Ischemia Biochemistry: Within seconds aerobic glycolysis , ATP Function & morphology: Within a minute rapid loss of contractility, ultrastructural changes reversible 20 40 minutes coagulation necrosis irreversiblePrompt interventionThrombolysis(溶栓)Angiop

18、lasty(血管成形术)Coronary arterial bypass graft(血管搭桥)MORPHOLOGY MI typically begins in the subendocardial region MI usually reaches its full size within 3 to 6 hoursPatterns of infarction Depending on The involved vessel The duration of the occlusion Metabolic demands of the myocardium Extent of collater

19、al supply 1. Transmural infarctions2. Subendocardial infarctions3. Microscopic infarcts Gross MIs less than 12 hours old usually are not grossly apparent By 12 to 24 hours after MI, an infarct usually can be grossly identified by a red-blue discoloration caused by stagnated, trapped blood Map-likeMi

20、croscopy Coagulation necrosis / inflammation Formation of granulation tissue Organization & scar- Acute MI Rupture Scar (remote infarction)“Irregular” map-like1 day - coagulation necrosis edema wavy fibers3-4 days Complete coagulation necrosis of myofibers Heavy neutrophilic infiltrate 7-10 days Wel

21、l-developed phagocytosis 3 wk Collagen fibers Granulation tissueScar - Rich collagen fibers - Residue myofibersReperfusion injury Restoration of blood flow greater damage Mitochondrial dysfunction; Myocyte hypercontracture; Free radicals; Leukocyte aggregation; Platelet and complement activationClin

22、ical Features The chest pain can not be relieved “Silent” infarcts are common in diabetic patients & elderly persons Rapid & weak pulse Diaphoretic & nauseous, particularly with posterior wall MIs Electrocardiographic abnormalities Q waves, ST segment changes, & T wave inversions lethal Arrhythmias

23、Laboratory evaluation Consequences & Complications of MI Depending on - infarct size - site - fractional thickness of the myocardial wall that is damaged 1. Contractile dysfunction Cardiogenic shock : massive MIs, involving 40% of the left ventricle 2. Arrhythmias Myocardial irritability & conductio

24、n disturbances Sudden death 3. Myocardial rupture Most common between days 3 -7 after MIs Papillary muscle; ventricular wall; ventricular septum4. Pericarditis5. Chamber dilation6. Infarct expansion 7. Mural thrombus thromboembolism8. Ventricular aneurysm - A late complication of large transmural MI

25、s - The bulging of the noncontractile fibrous myocardium during systole - A thin-walled, fibrous outpouching of the ventricular wall - Often with a mural thrombus 9. Progressive late heart failureChronic Ischemic Heart Disease The development of progressive congestive heart failure as a consequence

26、of long-term ischemic myocardial injuryCoronary arteries: moderate to severe atherosclerosisHeart: Gross - enlarged, left ventricular dilation and hypertrophy, patchy scars, mural thrombi Microscopy - myocardial hypertrophy, fibrosis, subendocardial myocyte vacuolizationClinical features: progressiv

27、e angina pectoris, MI, arrhythmiasSudden Cardiac Death Unexpected death from cardiac causes, occurring within 24h of the onset of symptoms Coronary artery diseases in adults Non-atherosclerotic causes in younger victimsA lethal arrhythmia, eg. Ventricular fibrillationHypertensionAdult blood pressure

28、 Grade Systolic pressure (mmHg) Diastolic pressure (mmHg)Normal = 130 = 140 and / or = 90Borderline 130 139 85 - 89Classification of Hypertension Essential (idiopathic) : 90 95% Arterioles / small arteries Benign : Malignant = 9 : 1 Secondary : diseases of adrenal glands, renal diseases, renal arter

29、y stenosisEssential (Primary, Idiopathic) Hypertension A chronic disease with spasm and sclerosis of arteriole and small artery caused by different factors, and eventually resulting in the lesions of organsPathogenesis The BP level is determined by the interaction of multiple genetic, environmental,

30、 and demographic factors that influence 2 hemodynamic variables: cardiac output and total peripheral resistance MORPHOLOGYHyaline arteriolosclerosis (benign hypertension)Hyperplastic arteriolosclerosisNecrotizing arteriolitis(malignant hypertension)Thickening of the walls with narrowing of the lumen

31、Processes of benign hypertension Stage 1: Functional disturbance Spasm of arteriole and small arteries Stage 2: Changes of vascular system Small artery & Arteriole hyaline degeneration Large & medial artery atherosclerosis Stage 3: Lesions of organs Heart - Hypertensive heart disease Left ventricula

32、r hypertrophy Early stage Concentric hypertrophy Later Acentric hypertrophy dilation of cardiac chambers LM: Myocytes hypertrophy, with prominent nuclear enlargement and hyperchromasia (“boxcar nuclei”) Interstitial fibrosisKidney Arterionephrosclerosis Gross symmetrically atrophic diffuse, fine gra

33、nularity of surface Microscopy hyaline arteriolosclerosis ischemic atrophy compensated hypertrophy & dilationArranged at intervals Brain Hypertensive encephalopathy Edema, softening (microinfarct), microaneurysms Hemorrhage: basal ganglia 基底核 （内囊） lenticulostriate artery (豆纹动脉 branching square from

34、arteriae cerebri media) Malignant hypertension Necrotizing arteriolitis: fibrinoid necrosis Hyperplastic arteriolosclerosis onion-skin, concentric, laminated thickening of the walls Benign vs Malignant Hypertension Benign MalignantIncidence high (90%)low (10%)Age middle or senior younger or middleBP

35、 140/90mmHg 200/120mmHg Symptom light severeLesion hyaline of arteriole fibrinoid necrosis of arteriole & small arteriesCourse 10yr 1 2yrCauses of death cerebral hemorrhage,renal failure, heart failureuremia (95%)Rheumatism(风湿病） Rheumatic fever is an acute, immunologically mediated, multisystem infl

36、ammatory disease. Following an episode of group A -hemolytic streptococcal infections (usually pharyngitis) after an interval of a few weeks Occuring in heart, synovium, joints, blood vessels, skin, etc. Acute rheumatic carditis Chronic valvular deformities After an initial attack, there is increase

37、d vulnerability to reactivation of the disease. Just like a crazy dog, licking all over the body and finally biting the heartEtiology and Pathogenesis Improved socioeconomic conditions Rapid diagnosis and treatment A hypersensitivity reaction induced by group A streptococci (1) Symptoms typically de

38、velop about 23 weeks after infection. (2) Streptococci are absent from the lesions. Antibodies directed against the M proteins of group A streptococci cross-react with normal proteins present in the heart, joints, and other tissues. The incidence and mortality An autoimmune response against self-ant

39、igens Genetic susceptibility Rheumatic fever occurs in only about 3% of patients with group A streptococcal pharyngitisMORPHOLOGYBasic pathologic changes 3 phases Necrotic & exudative phase Fibrinoid necrosis, inflammatory infiltrates Regeneration Rheumatic granuloma (rheumatic body, Aschoff body) F

40、ibrosisreoccurFibrinoid necrosis（纤维素样坏死）Rheumatic body (Aschoff body)- Often lie in close proximity to a small vessel- A central focus of fibrinoid necrosis surrounded by a chronic mononuclear inflammatory infiltrate - Aschoff cellsAschoff cellsRheumatic Heart Disease 1. Acute “ Pancarditis ”（全心炎） (

41、1) Rheumatic endocarditis Mitral (二尖瓣) 50%; Mitral +Aortic(二尖瓣+主动脉瓣) 50% Edematous, thickened, fibrinoid necrosis, verrucae(疣状物) (vegetation(赘生物), may resolve or progress) (2) Rheumatic myocarditis: Aschoff bodies (3) Rheumatic pericarditis: Fibrinous exudate (cor villosum(绒毛心), generally resolve wi

42、thout sequelae) Rheumatic endocarditis主动脉瓣二尖瓣Rheumatic myocarditis风湿小体Rheumatic pericarditis纤维蛋白性渗出浆液性渗出2. Chronic Characterized by organization of the acute inflammation & subsequent scarring Fibrous scar The mitral valves exhibit leaflet thickening, commissural fusion and shortening, and thickenin

43、g and fusion of the chordae tendineae. Valvular stenosis, regurgitation Microscopy: neovascularization, diffuse fibrosisthickening, commissural fusion and shortening of valvesFish mouth (mitral valve)Inflammatory neovascularizationPathologic Changes in Other Organs Rheumatic arthritis (风湿性关节炎) Large

44、r joints, migratory polyarthritis Without sequelae Skin Erythema annulare centrifugum (离心性环形红斑) subcutaneous nodules(皮下结节) Rheumatic arteritis (风湿性动脉炎) Brain Neuron degeneration, glia cell proliferation extrapyramidal(椎体外系) involved, chorea minor (小舞蹈病)Clinical Features Antibodies to one or more str

45、eptococcal enzymes Anti-Streptolysin O Signs Pericardial friction rubs Weak heart sounds Tachycardia(心动过速) or other arrhythmias Congestive heart failure 5% deathInfective Endocarditis Definition Infection of the cardiac valves or mural surface of the endocardium, resulting in the formation of bulky,

46、 friable vegetationCause Any type of microorganism, most by bacteria Antibiotic therapy blurs the distinction.A particularly difficult infection to eradicate because of the avascular nature of the heart valves.Classification Forms Organism ValvesAcute High virulence Previously normal Subacute Low vi

47、rulence Previously abnormalPathogenesis Conditions that increase the risk (1) Preexisting cardiac abnormalities: rheumatic heart disease (2) Prosthetic heart valves(瓣膜修复后): no difference between mechanical and bio-prosthetic valves (3) Host factors: DM, immunodeficiency, intravenous drug abuse Bacte

48、remia An infection elsewhere A previous dental, surgical or other interventional procedure, e.g. urinary catheterization (导尿管插入) Intravenous drug abusersMORPHOLOGY The hallmark is the presence of valvular vegetations containing bacteria or other organisms. Aortic and mitral valves are the most commo

49、n sites of infection. SBE “repair” ABE “damage” Causative organism low virulencea-hemolytic streptococci high virulencestaphylococcus aureusPathogenesisPreexisting abnormality Native valves Common sites mitral/aortic valves aortic valves Friable , bulky vegetations contain bacteria, single/multiple,

50、 1 valve Influence: type of organisms, degree of host reaction, previous antibiotic therapy Microscopically Platelet, fibrin, inflammatory infiltrates, bacteriaGranulation, fibrosis, calcification, chronic inflammatory infiltratesdestruction of the valves & vicinity, ring abscesses (in perivalvular

51、tissue) Sequelae chronic valvular disease, regurgitationRupture, sudden death, chronic valvular disease SBE “repair” ABE “damage”Sites other than heartSystemic emboli, anemic infarcts, GNSystemic emboli, septic infarcts (suppuration), ConsequenceHealing, chronic valvular diseaseDeath, SBEABE of aort

52、ic valveTricuspid valve, right atriumOften noted in intravenous drug abusersABE of aortic valve, multiple abscessesEmbolization via coronary artery Sterile & no microorgnisms Small to medium-sized, bland, nondestructive vegetations at the line of valve closure Usually found on previously normal valv

53、es Pathogenesis ? Subtle endothelial abnormalities; Hypercoagulable states; malignancies particular adenocarcinoma, SLE, etc. Nonbacterial Thrombotic Endocarditis (NBTE, 非细菌性栓塞性心内膜炎) Gross : Single or multiple nodules, along the valve closure, 5mm Microscopy : Platelet, fibrin & other blood componen

54、ts Consequences: Resolve spontaneously Lambls excrescences (delicate strands of fibrous tissue) Clinical features: Asymptomatic, systemic emboli & infarcts A potential nidus for bacterial endocarditisnon-bacterial thrombotic endocarditis NBTEComparison Between Diverse Valvular VegetationsSmall, wart

55、y(疣状), inflammatory vegetations, along the lines of valve closureIrregular, large, brisk destruction of chordae tendineaeEmbolizeSmall to medium, sterile, non-destructive, at the line of valve closureEmbolizeRheumaticendocarditisInfectiveendocarditisValvular Heart Diseases A diverse group of acquire

56、d or congenital lesions Stenosis: thick, rigid, commissural fusion , obstruction Incompetence (insufficiency): thick, rolling, shortening commissural fusion regurgitation Combined valvular disease (multivalvular disease) Stenosis and regurgitation coexistAnatomy of heart & blood flowMitral Stenosis

57、(二尖瓣狭窄) Cause: rheumatic heart disease Hemodynamic and heart changes: Early stage：hypertrophy & dilation of left atrium Late stage： edema and congestion of pulmonary hypertrophy and dilation of the right heart right Heart failure Clinical features: Diastolic murmur at the auscultation area of mitral

58、 valve Pink colored foamy sputum Mural thrombus, embolize Congestion of many organs二尖瓣狭窄附壁血栓形成“Pyriform Heart ”（梨形心）Mitral Regurgitation (二尖瓣关闭不全) Cause: rheumatic heart disease Hemodynamic and heart changes: Hypertrophy and dilation of the four chambers Left and Right Heart Failure Edema and conges

59、tion of pulmonary Pulmonary hypertension Clinical features: Systole murmur at the auscultation area of mitral valve Global Heart（球形心） Aortic Stenosis (主动脉瓣狭窄) Cause: rheumatic heart disease Hemodynamic and heart changes: Hypertrophy and dilation of the four chambers Left and right Heart Failure Edem

60、a and congestion of pulmonary Pulmonary hypertension Clinical features: Systole murmur at the auscultation area of Aortic Valve ; angina pectoris (心绞痛)Aortic Regurgitation (主动脉瓣关闭不全) Cause: rheumatic heart disease, infective endocarditis ; syphilitic arteritis Hemodynamic and heart changes: Hypertro