Contents
Arteriosclerosis Tumors of blood vessels Heart failure Ischemic heart disease Sakchai Chitpakdee, M.D. Valvular heart diseases Rheumatic heart disease Infective endocarditis Myocarditis Pericardial diseases
Arteriosclerosis
= hardening of the arteries y Atherosclerosis ○ Large & medium size vessels y Monckeberg medial calcific sclerosis ○ Medium size vessels with tunica media calcification y Arteriolosclerosis ○ Small arteries/arterioles
Atherosclerosis
“intimal lesion”: atheromas or fibrofatty plaques or atheromatous plaques” Large and medium size arteries y Raised focal plaque within the intima y Core lipid (cholesterol/cholesterol esters) and a covering fibrous cap y Cells: foamy cells (macrophage/SMC), lymphocytes Atherosclerosis
Complicated lesion: y Calcification y Rupture/ulceration -> atheroemboli, thrombus y Hemorrhage y Thrombosis y Aneurysmal dilation
Atherosclerosis
Epidemiology & risk factors: y Age: middle or later age y Sex: pre-menopause -> M > F 60s to 70s -> M = F y Genetics: familial y Hyperlipidemia: high cholesterol/TG & ↓ HDL y Hypertension y Cigarette smoking y Diabetes mellitus
Atherosclerosis Clinical features & prevention
Epidemiology & risk factors: Clinical features: y Elevated plasma homocysteine y Ischemic/infarction of organs y Other factors: y Atherosclerotic aneurysm ○ Competitive stressful lifestyle: type A personality Prevention: ○ Lack of exercise y Primary prevention: risk factor modification ○ Obesity y Secondary prevention: prevent recurrence of y Moderate intake of alcohol -> protective events or complications (antiplatlet drugs etc) factor Tumors Tumors
Benign neoplasms: Intermediate-grade neoplasms: y Hemangioma: capillary, cavernous, pyogenic y Kaposi sarcoma granuloma y Hemangioendothelioma y Lymphangioma: simple (capillary), cavernous lymphangioma (cystic hygroma) Malignant neoplasms: y Glomus tumor, myopericytoma y Angiosarcoma y Vascular ectasia: nevus flammeus, spider y Hemangiopericytoma (benign & malignant) telangiectasia, hereditary hemorrhagic telangiectasia (osler-Weber-Rendu dis.) y Bacillary angiomatosis: B. henselae infection
Hemangioma Hemangioma
Pyogenic granuloma (lobular capillary) Capillary hemangioma: y Polypoid nodules of skin, gingiva, oral y Skin, subcutaneous tissue, oral cavities of head mucosa and neck, lung, liver, kidney y Bleeding, ulcerated y Strawberry type (juvenile hemangioma): 1:200 y Granuloma gravidarum: 1% pregnant newborns: fade 1-3 yr, regress by 7 yr women, pyogenic granuloma at gingiva, Cavernous hemangioma: regress after delivery y Older age, less circumscribed, deeper y No regress
Lymphangioma
Lymphangioma circumscriptum (capillary ymphangioma) y Subcutaneous mass of head and neck Cavernous lymphangioma y Cystic hygroma y Neck and axilla of children y Turner syndrome: neck region Vascular ectasia Kaposi sarcoma
Nevus flammeus: Chronic, classic european KS y Birthmark of head and neck, flat Lymphadenopathy, African, endemic KS y Pink to purple Æ regress Transplant-associated Port-wine stain: no regress (immunosuppression-associated) KS y Trigeminal nerve Æ Sturge-Weber syndrome (ecephalotrigemina AIDS-associated KS angiomatosis), venous mass of Clinical: patchesÆ plaquesÆ nodules leptimeninges Æ seizure, hemiplegia, mental retardation Cause: HSV-8, HIV?
Angiosarcoma
Malignant endothelial neoplasms Skin, soft tissue, breast, liver Cause: y Breast: radiation, lymphedema y Liver: polyvinyl chloride (PVC), throrotrast y Skin: arsenic (pesticide)
Heart failure Left-side heart failure
Cause: IHD, HT, aortic & mitral valve CHF = congestive heart failure disease, cardiomyopathy Common end result of many forms of HD Clinical: Unable to pump blood at rate of body y Forward effect: poor organ perfusion requirement (prerenal azotemia, hypoxic Progressive deterioration of myocardial encephalopathy) contraction y Backward effect: pulmonary edema y Systolic dysfunction (dyspnea, orthopnea, PND) y Diastolic dysfunction Right-side heart failure What is Ischemic Heart Disease?
Cause: pulmonary HT (cor pulmonale) Myocardial ischemia Hypertrophy of right ventricle, atrium, Imbalance btw supply (perfusion) & demand of septum Æ left-side HF oxygenated blood Clinical: Ischemia Æ ↓Oxygen y Forward effect: poor oxygenation Æ ↓ Nutrient substrates y Backward effect: organ edema, effusion Æ ↓ Metabolites removal Ischemia Æ Dysfunction of pumping Æ Abnormal heart rhythms Æ Myocardial infarction (Necrosis)
Etiology of IHD Clinical manifestation
90 % Æ coronary artery Four syndromes: atherosclerosis 1. Myocardial infarction 2. Angina pectoris: variants y Atherosclerosis Æ narrow lumen 1. Stable angina Æ thrombus formation 2. Prinzmetal angina Æ coronary vasospasm 3. Unstable angina 3. Chronic ischemic heart disease Others: hypertrophy, hypovolemia, 4. Sudden cardiac death hypoxemia,↑ heart rate
Clinical manifestation Role of fixed coronary obstruction
At least 75 % reduction of cross- Stable plaque Æ Unstable plaque sectional area (insufficient compensatory Stable angina Æ Acute coronary vasolidation) syndromes At least 90 % reduction Æ ischemia at rest Acute coronary syndromes: Atherosclerosis type IV-VI unstable angina, acute MI, and Affected location: proximal (LAD, LCX), sudden death entire (RCA) Role of acute plaque change
Acute plaque change/disruption: y Hemorrhage into atheroma Æ ↑ volume y Rupture or fissuring Æ Thrombosis y Erosion or ulceration Æ Thrombosis
A = Plaque rupture B = Thrombus over plaque rupture C = Massive plaque rupture with thrombus
Angina pectoris Angina pectoris
Paroxysmal and usually recurrent attacks of Stable angina: substernal or precordial chest discomfort caused by y Most common, and predictable transient (15 sec to 15 min) myocardial ischemia y Reduction of coronary perfusion by chronic that falls short of inducing cellular necrosis (infarct) stenosing coronary atherosclerosis Three patterns: y Pain brought by physical excertion, emotional y Stable or typical angina stress, heat or cold fever, anemia etc y Prinzmetal or variant angina y Pain relieved by rest (decreased demand) or y Unstable or crescendo or accelerating or nitroglycerin (vasodilator) preinfarction angina y Monitoring ECG: ST segment depression or elevation or T-wave inversion
Angina pectoris Angina pectoris
Prinzmetal variant angina: Unstable angina: y Uncommon, and unpredictable y Angina occurring with increasing frequency, y Occur at rest not related to physical and emotional precipitated with less effort, often occurs at exertion rest and tends to be prolonged duration y Coronary artery vasospasm y Most induced by disruption of atherosclerotic plaque with partial thrombosis and possibly y Atherosclerosis-induced hypercontractility, embolization or vasospasm vasospastic chemicals secretion by mast cells and abnormal calcium influx y Harbinger of subsequent acute MI y Response well to calcium-channel blockers and y Thrombus labile and lasts 20 to 30 minutes nitroglycerin y 10 to 15% total occlusion Å collateral vessel y ECG: elevation of ST-segment Myocardial infarction Myocardial infarction
Necrosis of myocardium Transmural (Q-wave) infarction Prolonged period of ischemia at rest lasting > y Full or nearly full thickness necrosis 20 min, unresponsive to NTG y Acute plaque change + completely obstructive Ischemic ECG change and positive cardiac thrombosis (fixed and persist > 1 hour) enzymes y ECG: ST segment elevation Æ Q wave Subendocardial (Non-Q-wave) infarction 25 % silent: old age, diabetics y 1/3 to ½ inner ventricle thickness necrosis Subendocardial VS Transmural infarction y Incomplete obstructive thrombosis (>30-40 min) y Non-Q-wave VS Q-wave infarction y ¼ complete obstruction + collateral supply y ECG: ST segment elevation Æ Non-Q-wave
Morphological change
Almost all transmural MI involve at least a portion of left ventricle Coronary arteries and MI site: y LAD (40-50%) -> ant wall of LV, apex, ant portion of ventricular septum y RCA (30-40%) -> inf-post wall of LV, post portion of ventricular septum, RV (inf-post) y LCX (10-20%) -> lateral wall LV except apex
1 day 3 to 4 days
7 to 10 days 3 weeks Evolution of morphology change Cardiac enzymes Time Morphology change 0 - ½ hours Ultrastructural change (EM) Released enzymes after myocardial cell
2 – 3 hours Triphenyltetrazolium chloride dye: dead: noninfarct area Æ brick-red, infarcted Æ unstained y Myoglobin 4 – 24 hours Gross: dark mottling area, y Troponin (TnI and TnT) Histology: hemorrhage and necrosis y Creatine kinase (total CK and CK-MB) 1 – 7 days Gross: yellow-tan mottling, reddish border Histology: neutrophils and macrophages y LDH (LDH1, LDH2) 7 – 14 days Gross: red-tan margin Histology: macrophages and granulation tissue 2 – 8 weeks Gross: gray-white scar Histology: collagen deposition > 2 months Scarring complete
Cardiac enzymes Consequences and complications
7x Myoglobin 6x Total CK 50 % AMI Æ dead Half of dead occur within 1 hour (VF) 5x In-hospital death rate 30% Æ 10-13 % 4x 75 % develop one or more complications LDH 3x y Contractile dysfunction Æ cardiogenic shock 10 – 15 % of AMI and 70 % mortality rate 2x CK-MB Troponin I y Arrhythmias Æ sudden death Upper limit of normal serum level of normal limit Upper 1x bradycardia, tachycardia, VPC, VT, VF asystole 0 20 40 60 80 100 120 140 160 Hours from onset of infarction
Consequences and complications Consequences and complications
Ventricular aneurysm Æ thrombus, Myocardial rupture: arrhythmias, heart failure, rupture y Ventricular free wall Æ cardiac temponade Papillary muscle dysfunction Æ MR y Ventricular septum Æ left-to-right shunt Progressive late heart failure y Papillary muscle Æ acute MR Pericarditis Infarct extension and expansion Mural thrombus Æ thromboembolism Apical left ventricular Rupture ventricular aneurysm septum
Wall thinning and Rupture papillary mural thrombus muscle
Cardiac rupture Fibrinous Pericarditis
Prognosis Treatment
Extent and location of infarction Decrease myocardial oxygen demand Quality of left ventricular function Increase myocardial oxygen supply Monitoring and treat complication Previous cardiovascular health Decrease myocardial oxygen demand: Age, female gender & other diseases y Preload & afterload reduction Total mortality for 1st year = 30 % y HR control, pain relief, activity restriction 3 – 4 % mortality with each passing year Increase oxygen supply: y Oxygen administration y Antiplatelet therapy (aspirin), thrombolytic drug y Angioplasty(PTCA), atherectomy, CABG
Infarct modification after reperfusion Thrombolysis: Enzymatic digestion of thrombus to open lumen Early reperfusion: y Salvage ischemic myocardium (15-20 min) Percutaneous y Limit infarct size (after longer interval) transluminal coronary angioplasty Critical period: first 3 – 4 hours (PTCA): Physical disruption of Thrombolytic Rx: streptokinase, and tissue plaque to open lumen type plasminogen activator (tPA), reteplase (rPA) Coronary artery bypass grafting PTCA: eliminate thrombus and relieve some (CABG): underlying atherosclerotic plaque Surgical placement of a new conduit to bypass occlusion Chronic ischemic heart disease Sudden cardiac death
Progressively develop heart failure as a Unexpected death from cardiac causes consequence of ischemic myocardial damage early (usually within 1 hour) Ischemic cardiomyopathy Causes: y After MI Æ cardiac decompensation of y Majority IHD hypertrophic noninfarcted myocytes y Others: congenital structural or coronary arterial y No MI Æ severe obstructive coronary disease abnormalities ○ Aortic valve stenosis, mitral valve prolapse Æ diffuse myocardial dysfunction ○ Myocarditis ○ Dilated and hypertrophic cardiomyopathy Mechanism: arrhythmia (Asystole, VF)
Endocardial and valvular diseases Major causes
Stenosis = failure of a valve to open Mitral valve stenosis: completely y Postinflammatory scarring (RHD) Mitral valve regurgitation: y Abnormalities of leaflets and commissures Regurgitation/Insufficiency = Inability of ○ Postinflammatory scarring a valve to close completely ○ Infective endocarditis ○ Floppy mitral valve (Prolapse) y Abnormalities of tensor apparatus ○ Rupture of papillary muscle/cordae tendinae
Major causes
Aortic stenosis: y Postinflammatory scarring (RHD) y Senile calcific aortic stenosis y Calcification of a congenitally deformed valve Aortic regurgitation y Postinflammatory scarring y Infective endocarditis y Aortic diseases: Syphilitic aortitis, Marfan syndrome, Rheumatoid arthritis Disorders of Mitral valve
Mitral stenosis: y Abnormal Lt. atrial-Lt. ventricular pressure gradient during diastole y Atrial enlargement and hypertrophy y SevereÆ PHT, Rt. Ventricular hypertrophy, Rt. HF y Clinical: Dyspnea, orthopnea, weakness, Dysarrhythmia (AF) Æ emboli
Disorders of Mitral valve Disorders of Aortic valve
Mitral regurgitation: Aortic stenosis: y Elevation of Lt. atrial volume and pressure y Lt. ventricular-aortic pressure gradient y Lt. atrial and ventricle dilate and hypertrophy y Lt. ventricular hypertrophy y Severe: Lt. HF, pulmonary congestion y Severe: myocardial ischemia, Lt. HF y Clinical: Anginal pain, syncope, fatigue and low systolic blood pressure
Rheumatic fever and Rheumatic heart Disorders of Aortic valve disease
Aortic regurgitation: Rheumatic fever: y Lt. Ventricle volume overload y acute, immunologically mediated y Lt. Ventricular hypertrophy and dilation multisystem inflammatory disease y Severe: Lt. HF y occurs a few weeks after an episode of group A (beta-hemolytic) streptococcal y Clinical: palpations, trobbing heart (large stroke volume) pharyngitis y acute rheumatic carditis may progress to chronic valvular deformities Rheumatic fever- Diagnosis Jones criteria
Jones criteria: Major criteria: y 2 major criteria or y Carditis y 1 major and 2 minor criteria y Polyarthritis (Migratory) plus y Chorea (Sydenham) y evident of antecedent group A y Erythema marginatum of skin streptococcal infection y Subcutaneous nodules ○ positive throat culture ○ positive group A strep. antigen test ○ elevated serum anti-strep. antibody titer
Jones criteria Rheumatic heart disease
Minor criteria: Acute rheumatic fever: Carditis y Clinical findings: y Endocarditis, myocarditis, pericarditis ○ Arthralgia y Pancarditis ○ Fever y Aschoff bodies, Antischkow cells (Pathognomonic), Aschoff giant cells y Laboratory findings: Chronic rheumatic heart disease: ○ Elevated acute phase reactant (ESR,CRP) y deformed fibrotic valves (MV>AV>TV>PV) ○ Prolonged PR interval on ECG y Frequent cause of MS (99% of cases)
Pathogenesis
hypersensitivity reaction induced by group A streptococcal Streptococcal antigens (M protein) that cross-react with human tissue through molecular mimicry Most ARF-associated strains: M type 3, 1, 18, 5 and 6 M protein: antiphagocytic surface antigens Clinical Features Treatment
ARF occurs 10 days to 6 weeks (usu. anti-streptococcal therapy: within 3 wks) after pharyngitis y IM benzathine penicillin most often in children age of 5 to 15 y 10 days oral penicilin or erythromycin years old anti-inflammatory therapy: 1/3 of ARF patients has no history of y oral salicylates previous pharyngitis y corticosteroid (prednisolone) with severe Serologic study: antistreptolysis-O cases of carditis (ASO) or antideoxyRNase B (anti- Prophylaxis: antibiotics given 5 yrs to DNase B) titer lifetime prophylaxis
Infective endocarditis Infective endocarditis
caused by invasion and colonization of Acute endocarditis: endocardial structures by y destructive infection, frequently in normal heart microorganisms which resulting in valve, with highly virulent organisms inflammation y leads to death within days or weeks of > 50% y bacteria (most common): bacterial of patients endocarditis Subacute endocarditis: y fungi, rickettsiae (Q fever) and clamydiae: y infection with low virulent organisms in uncommon abnormal heart y disease appears insidious and protracted course
Cause and Pathogenesis Cause and Pathogenesis
Cardiac and vascular abnormalities: Host factors: y rheumatic heart disease y neutropenia y myxomatous mitral valve (MVP) y immunodeficiency y degenerative calcified valvular stenosis y therapeutic immunosuppression y bicuspid aortic valve y diabetic mellitus y artificial (prosthesis) valves y alcohol y vascular grafts y intravenous drug abuse Cause and Pathogenesis
Causative organisms: ○ alpha-hemolytic (viridans) streptococci (50- 60%) ○ S. aureus (10-20%) ○ HACEK group: Haemophilus, Actinobacillus, Cardiobacterium, Eikenella and Kingella) ○ S. epidermidis in prosthetic valve ○ 10% Æ culture negative endocarditis y previous antibiotic therapy y difficult to culture or deep enbedded organism
Cause and Pathogenesis Clinical features
Portal of entry: Subacute endocarditis y dental or surgical procedure y Fever (Prolonged) y infection at other site y non-specific symptoms: fatigue, weight loss flulike syndrome y injection eg. IVDUs y Murmurs (90% in left-side disease) y occult sources from gut, oral cavity, or y Others: petechiae, subungual hemorrhage, trivial injuries Roth spots in the eyes (microemboli) Acute endocarditis: fever, chills, Æ antibiotic prophylaxis weakness, murmur, CHF
Complications
Cardiac complications: y valvular insufficiency or stenosis y cardiac failure y myocardial ring abscess with perforation y suppurative pericarditis y prothesis valve leakage or dehiscence Embolic complications: y Left-side: brain, MI, spleen, kidneys y Right-side: lung infection Myocarditis Causes of myocarditis
Inflammatory process of the Infections: myocardium resulting in injury of cardiac y Viruses: Coxsackies virus, ECHO, influenza, HIV, CMV myocytes y Clamydiae: C. psittaci Causes: y Rickettsiae: R. typhi typhus fever y infections y Bacteria: Diphtheria, N. Meningitidis, Borrelia Lyme disease y Immune-mediated y Fungi: Candida y others: sarcoidosis, giant cell myocarditis y Protozoa: Trypanosoma chagas disease, toxoplamosis y Helminths: trichinosis
Causes of myocarditis
Imune-mediated reactions: y Postviral y Poststreptococcal (rheumatic) y SLE y Drugs: Methydopa, sulfonamides y Transplant rejection Unknown causes: y sarcoidosis y Giant cell myocarditis
Clinical features Pericardial effusion
Asymptomatic Æ complete recovery Accumulation of noninflammatory fluid in the pericardial sac (normal 30 – 50 mL Arrhythmias of fluid) Cardiomegaly Æ functional valvular Cardiac tamponade = external regurgitation compression of the heart chambers Heart failure Æ death resulting in filling impair Develop DCM years later y Æ ↓ stroke volume, HR ↑ y Rx: pericardiocentesis Diagnosis: endomyocardial biopsy Pericarditis
Inflammation of the pericardium Acute pericarditis: y Serous/ fibrinous/ purulent/ hemorrhagic/ caseous y Fever, tachycardia, chest pain, pericardial friction rub Chronic pericarditis: y Constrictive pericarditis/ adhesive mediastinopericarditis
References
1. Ramzi S. Cotran: Robbins’ Pathologic Basis of disease, 6th ed. Philadelphia, WB Sauders, 1999 2. Copstead Banasik: Pathophysiology biological and behavioral perspective, 2nd ed 3. Baunwald: Heart disease: A textbook of Cardiovascular Medicine, 6th ed. Philadelphia, WB Sauders, 2001 4. Eugene Braunwald: Cardiovascular diseases: Harrison’s Manual of Medicine, 15th ed. McGraw- Hill, 2002