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  1. 1. PATHOPHYSIOLOGY OF CARDIOVASCULAR DISEASE (CVD) <ul><li>leading cause of death in the U.S. for men and women </li></ul><ul><li>42% of all deaths (1 out every 2.4 deaths) </li></ul><ul><li>an average of one death every 33 seconds </li></ul>
  2. 2. CARDIOVASCULAR DISEASE <ul><li>claims as many lives as the other top 8 causes of death combined </li></ul><ul><li>1/6th are under age 65 </li></ul><ul><li>From 1984 -1994 CVD deaths declined 22% (although the actual number of deaths dropped only 3%) </li></ul>
  3. 3. CARDIOVASCULAR DISEASE <ul><li>includes: </li></ul><ul><li>coronary artery disease </li></ul><ul><li>stroke </li></ul><ul><li>hypertension </li></ul><ul><li>congenital heart disease </li></ul><ul><li>valvular heart disease </li></ul><ul><li>rheumatic heart disease </li></ul><ul><li>arrhythmias </li></ul>
  4. 4. CARDIOVASCULAR DISEASE <ul><li>Coronary Artery Disease (CAD) or Coronary Heart disease (CHD) </li></ul><ul><ul><li>single leading cause of death in the U.S. (20% of all deaths) </li></ul></ul><ul><li>May result in: </li></ul><ul><ul><li>angina pectoris </li></ul></ul><ul><ul><li>myocardial infarction </li></ul></ul><ul><ul><li>sudden cardiac death </li></ul></ul><ul><ul><li>congestive heart failure </li></ul></ul><ul><li>KEY TERMS: Pg 412 Resource Manual </li></ul>
  5. 5. Myocardial Infarction <ul><li>1.5 million myocardial infarctions (MI’s) per year </li></ul><ul><ul><li>500,000 fatal </li></ul></ul><ul><ul><li>250,000 die within an hour of onset (sudden MI) </li></ul></ul>
  6. 6. Myocardial Infarction <ul><li>13.5 million alive today with history of MI </li></ul><ul><li>5% of MI in people under 40 years old </li></ul><ul><li>45% under 65 years old </li></ul><ul><li>In 48% of men and 63% of women who died suddenly of MI, there were no previous symptoms </li></ul>
  7. 7. Coronary Heart Disease <ul><li>atherosclerosis </li></ul><ul><ul><li>progressive build-up of plaque on the inside of the artery wall </li></ul></ul><ul><ul><li>large arteries </li></ul></ul><ul><li>arteriosclerosis </li></ul><ul><ul><li>“ hardening” of the arteries </li></ul></ul><ul><ul><li>thickening of arterial wall </li></ul></ul><ul><ul><li>loss of elastic tissue </li></ul></ul>
  8. 8. Coronary Heart Disease <ul><li>Causes of Atherosclerosis </li></ul><ul><li>Risk factors - increase the probability of developing the disease </li></ul><ul><li>Primary or major risk factors (pg 415) : </li></ul><ul><li>hypertension </li></ul><ul><li>dyslipidemia </li></ul><ul><li>cigarette smoking </li></ul><ul><li>physical inactivity </li></ul><ul><li>obesity </li></ul>
  9. 9. Coronary Heart Disease <ul><li>Secondary risk factors </li></ul><ul><li>diabetes </li></ul><ul><li>personality type / stress </li></ul><ul><li>family history of CHD </li></ul><ul><li>age </li></ul><ul><li>gender </li></ul><ul><li>race </li></ul>
  10. 10. Coronary Heart Disease <ul><li>Risk factors </li></ul><ul><li>Key Terms – pg 96 Resource Manual </li></ul><ul><li>Other classification scheme – Box 5-1 pg 97 </li></ul><ul><li>Lipid classification: </li></ul><ul><ul><li>Box 5-2 pg 98-100 </li></ul></ul><ul><li>Blood pressure pg 103 </li></ul><ul><li>Obesity pg 104 </li></ul><ul><li>Emerging risk factors </li></ul><ul><li>Framingham Risk Assessment </li></ul>
  11. 11. Coronary Arteries <ul><li>Normal coronary arteries </li></ul><ul><ul><li>left main </li></ul></ul><ul><ul><li>left anterior descending (LAD) </li></ul></ul><ul><ul><li>circumflex </li></ul></ul><ul><ul><li>right coronary artery </li></ul></ul><ul><ul><li>posterior descending artery (PDA) </li></ul></ul>
  12. 14. Process of Atherosclerosis <ul><li>Atherosclerosis - lesions of the large and medium-sized arteries with deposits in the intima of yellowish plaques containing cholesterol, lipoid material , and lipophages </li></ul><ul><li>3 stages of development </li></ul><ul><ul><li>Intimal thickening- reversible </li></ul></ul><ul><ul><li>Fatty streaks - reversible </li></ul></ul><ul><ul><li>Fibrous plaques - irreversible (at least for the most part) </li></ul></ul>
  13. 15. Process of Atherosclerosis <ul><li>Endothelium or endothelial layer (figure 29-1 pg 412): </li></ul><ul><li>lines inside of arterial walls </li></ul><ul><li>in direct contact with blood </li></ul><ul><li>controls passage of substances from blood into arterial wall </li></ul><ul><li>Anti-thrombotic = inhibit blood clots </li></ul>
  14. 16. Process of Atherosclerosis <ul><li>Endothelial Cells: </li></ul><ul><li>Produce several vasoactive substances </li></ul><ul><ul><li>Prostacyclin - vasodilator; antithrombotic </li></ul></ul><ul><ul><li>Endothelial derived relaxing factor (EDRF) or nitric oxide - inactivates platelets; inhibits smooth muscle cell migration and proliferation </li></ul></ul>
  15. 17. Process of Atherosclerosis <ul><li>Endothelial Cells </li></ul><ul><li>under normal conditions - protect against the development of atherosclerosis </li></ul><ul><li>when damaged - play a major role in its development </li></ul><ul><li>Box 29-1 pg 413 - causes of endothelial injury </li></ul>
  16. 18. Process of Atherosclerosis <ul><li>layers of the artery </li></ul><ul><ul><li>intima </li></ul></ul><ul><ul><li>media </li></ul></ul><ul><ul><li>adventitia - contain collagen, elastin, and fibroblasts; contain the vasa vasorum = small blood vessels </li></ul></ul>
  17. 20. Process of Atherosclerosis <ul><li>Smooth muscle cells </li></ul><ul><li>located primarily in the medial layer </li></ul><ul><li>contractile </li></ul><ul><li>synthetic </li></ul><ul><ul><li>sensitive to growth promoting factors(prolifitive) and migrating factors </li></ul></ul>
  18. 21. Process of Atherosclerosis <ul><li>Platelets </li></ul><ul><li>tiny cells in the blood stream that repair “holes” in the arterial wall (intima) </li></ul><ul><li>“ platelet plug” prevents blood loss </li></ul><ul><li>prothrombotic - clot forming </li></ul><ul><li>Monocytes and Macrophages </li></ul><ul><li>cells of the immune system </li></ul><ul><li>activated at sites of arterial injury </li></ul>
  19. 22. Process of Atherosclerosis <ul><li>Fibroblasts </li></ul><ul><li>type of connective tissue </li></ul><ul><li>in response to growth factors, migrate from the media to intima and synthesize fibrous tissue (along with smooth muscles) </li></ul><ul><li>Foam Cells </li></ul><ul><li>cells formed from other cells such as macrophages which release cholesterol into the extracellular space giving rise to fatty streaks </li></ul>
  20. 23. Process of Coronary Artery Disease <ul><li>Injury hypothesis of CAD </li></ul><ul><li>endothelial disruption is the first step in a series of events </li></ul><ul><li>risk factors may be involved in causing the initial injury </li></ul><ul><li>Box 29-1 pg 413 Resource Manual - list of factors that may result in endothelial injury </li></ul><ul><li>“ Inflammatory response”: Box 29-2 pg 413 </li></ul>
  21. 24. Process of Coronary Artery Disease <ul><li>Following endothelial injury, a number of pathologic events occur which often lead to narrowing of the arterial lumen diameter </li></ul><ul><li>Endothelial disruption can lead to: </li></ul><ul><ul><li>mitogenic effects - growth of tissues /cells </li></ul></ul><ul><ul><li>chemotactic effects - migration of cells </li></ul></ul><ul><li>Injury hypothesis of CAD </li></ul><ul><ul><li>figure 29.2 Resource Manual </li></ul></ul>
  22. 25. Process of Coronary Artery Disease <ul><li>Relationship of cardiovascular disease risk factors to the “Injury hypothesis” </li></ul><ul><ul><li>tobacco use - Box 29-3 pg 415 </li></ul></ul><ul><ul><li>diabetes - Box 29-4 pg 415 </li></ul></ul><ul><ul><li>hypertension </li></ul></ul><ul><ul><li>dyslipidemia </li></ul></ul>
  23. 26. Process of Atherosclerosis <ul><li>progression of atherosclerosis is non-linear </li></ul><ul><ul><li>some lesions are stable over many years </li></ul></ul><ul><ul><li>some progress rapidly within months </li></ul></ul><ul><li>Rupture of Fissuring of plaques </li></ul><ul><ul><li>from turbulent flow or chemical factors </li></ul></ul><ul><ul><li>may lead to mural thrombi (platelet aggregation) of varying sizes at these sites </li></ul></ul><ul><ul><li>Thrombi may be incorporated into the plaque during this process </li></ul></ul>
  24. 28. Process of Atherosclerosis <ul><li>Coronary atherosclerosis can occur diffusely (long length of artery) with occasional discrete, localized areas of more pronounced narrowing of the vessel lumen that may produce obstruction of blood flow. </li></ul><ul><li>Non-atherosclerotic coronary obstructions </li></ul><ul><ul><li>Coronary vasospasm </li></ul></ul><ul><ul><li>Intracoronary thrombus </li></ul></ul>
  25. 29. Atherosclerotic Plaques <ul><li>Described as “percent occlusion” or “percent stenosis” </li></ul><ul><ul><li>Example 90% stenosis of the LAD </li></ul></ul><ul><li>Obstructive coronary atherosclerosis is used to describe CAD that is severe enough to reduce blood flow </li></ul><ul><li>Severity of coronary atherosclerosis is detected using coronary angiography </li></ul><ul><ul><li>coronary angiogram </li></ul></ul>
  26. 31. Atherosclerotic Plaques <ul><li>Regression of CAD using non-invasive interventions </li></ul><ul><ul><li>Diet </li></ul></ul><ul><ul><li>Exercise </li></ul></ul><ul><ul><li>Medications </li></ul></ul>
  27. 32. Treatment Options for CAD <ul><li>“ Revascularization” Procedures </li></ul><ul><ul><li>Percutaneous Transluminal Coronary Angioplasty (PTCA) </li></ul></ul><ul><ul><li>Coronary Artery Bypass Surgery (CABS) or Coronary Artery Bypass Graft (CABG) surgery </li></ul></ul><ul><ul><li>Coronary Atherectomy and Rotablator </li></ul></ul><ul><ul><li>Laser Angioplasty </li></ul></ul>
  28. 33. <ul><li>P ercutaneous T ransluminal C oronary A ngioplasty (PTCA) </li></ul>
  29. 36. Coronary Obstructions After Cardiac Interventions <ul><li>Restenosis - reocclussion of obstructive lesion </li></ul><ul><li>Tend not to be as lipid rich as original plaque and are highly related to thrombosis </li></ul><ul><li>Approximately 35% at 5 years from original CABS </li></ul><ul><li>Approximately 45% at 6 months for PTCA </li></ul><ul><li>Restenosis rate reduced using coronary stents after PTCA </li></ul>
  30. 37. Progression of Atherosclerosis <ul><li>Rate of progression is highly related to number and severity of risk factors </li></ul><ul><ul><li>Native vessels </li></ul></ul><ul><ul><li>Saphenous vein grafts </li></ul></ul><ul><ul><li>Internal mammary grafts </li></ul></ul><ul><ul><li>After PTCA and other interventions </li></ul></ul>
  31. 38. Exercise and Atherosclerosis <ul><li>Independently reduces risk of CAD </li></ul><ul><li>Slows rate of progression by acting on other risk factors </li></ul><ul><li>Increases fibrinolytic activity </li></ul><ul><li>May stimulate the formation of collateral vessels when one or more obstructive lesions are present </li></ul>
  32. 40. Manifestations of Coronary Atherosclerosis: Coronary Blood Flow <ul><li>heart - completely aerobic organ </li></ul><ul><li>coronary blood flow = “myocardial oxygen “supply” </li></ul><ul><li>oxygen requirements of the myocardium = myocardial oxygen “demand” </li></ul><ul><li>at rest, myocardium extracts 85% or more of oxygen from blood </li></ul><ul><li>exercise: 5-6 fold increase in coronary blood flow </li></ul>
  33. 41. Coronary Blood Flow <ul><li>Normal conditions: coronary supply is closely regulated to myocardial O 2 demand </li></ul><ul><li>auto regulation </li></ul><ul><li>factors of myocardial oxygen demand: </li></ul><ul><ul><li>heart rate </li></ul></ul><ul><ul><li>stroke volume </li></ul></ul><ul><ul><li>cardiac output </li></ul></ul><ul><ul><li>systolic blood pressure </li></ul></ul><ul><ul><li>total peripheral resistance </li></ul></ul>
  34. 42. Coronary Blood Flow <ul><li>Determined by arterial pressure and vascular resistance </li></ul><ul><li>intramyocardial pressure also affects coronary flow </li></ul><ul><ul><li>systole vs. diastole (figure 29.5 pg 417 Resource Manual) </li></ul></ul><ul><li>reduction of luminal diameter reduces flow </li></ul><ul><ul><li>luminal area obstruction of > 75% causes blood flow reduction at rest </li></ul></ul><ul><ul><li>“ hemodynamically significant lesion” </li></ul></ul>
  35. 43. Coronary Blood Flow <ul><li>Atherosclerotic arteries have limited ability to vasodilate </li></ul><ul><li>Atherosclerotic arteries are deficient in EDRF (nitric oxide) which increase likelihood of a mural thrombus </li></ul>
  36. 44. Myocardial Ischemia <ul><li>coronary blood flow does not adequately meet myocardial oxygen demand </li></ul><ul><li>results in progressive abnormalities in cardiac function = ischemic cascade </li></ul><ul><ul><li>stiffening of the left ventricle </li></ul></ul><ul><ul><li>results in decreased diastolic filling (diastolic dysfunction) </li></ul></ul><ul><ul><li>impaired systolic emptying </li></ul></ul><ul><ul><ul><li>hypokinesis, akinesis, dyskinesis </li></ul></ul></ul>
  37. 45. Myocardial Ischemia <ul><li>Systolic impairment demonstrated by </li></ul><ul><ul><li>segmental wall motion abnormalities </li></ul></ul><ul><ul><li>reduction in left ventricular ejection fraction </li></ul></ul><ul><ul><li>reduced stroke volume </li></ul></ul><ul><li>echocardiogram </li></ul><ul><ul><li>“ stress echo” </li></ul></ul>
  38. 46. Myocardial Ischemia <ul><li>EKG changes </li></ul><ul><ul><li>ST segment depression </li></ul></ul><ul><ul><li>ST segment elevation </li></ul></ul><ul><ul><li>T wave inversion </li></ul></ul><ul><ul><li>ventricular arrhythmias </li></ul></ul>
  39. 47. Myocardial Ischemia <ul><li>reversible </li></ul><ul><li>no permanent cardiac damage </li></ul><ul><li>prolonged ischemia </li></ul><ul><ul><li>irreversible damage may occur = necrosis of myocardial tissue (myocardial infarction) </li></ul></ul>
  40. 48. Angina Pectoris <ul><li>heart pain due to myocardial ischemia </li></ul><ul><li>characteristics of “typical” or “classic” </li></ul><ul><ul><li>pressure, tightness, squeezing, heaviness, or choking </li></ul></ul><ul><ul><li>radiates down left arm, back, and/or jaw </li></ul></ul><ul><ul><li>occurs with physical activity, emotional stress, cold weather, heavy meals </li></ul></ul><ul><ul><li>last few minutes or until activity ceases </li></ul></ul>
  41. 49. Myocardial Ischemia <ul><li>angina pectoris </li></ul><ul><ul><li>relieved with rest </li></ul></ul><ul><ul><li>nitroglycerin </li></ul></ul><ul><li>stable angina </li></ul><ul><li>atypical angina </li></ul><ul><li>unstable angina </li></ul><ul><li>Prinzmetal’s angina </li></ul>
  42. 51. STABLE CAD <ul><li>Presence of hemodynamicaly significant lesion(s) </li></ul><ul><li>anatomically stable lesions that result in: </li></ul><ul><ul><li>predictable, reproducible ischemia and/or angina </li></ul></ul>
  43. 52. Myocardial Infarction <ul><li>Result of severe, prolonged (>60 min) ischemia in the presence or absence of angina </li></ul><ul><li>irreversible heart muscle damage - necrosis </li></ul><ul><li>MI can occur in lesions with less than 50% stenosis </li></ul><ul><ul><li>rupture prone plaques </li></ul></ul><ul><ul><li>explains why many persons who experience MI do not report a history of angina before infarction </li></ul></ul>
  44. 53. Acute MI <ul><li>Thickness of walls affected: </li></ul><ul><ul><li>transmural infarction - Q wave </li></ul></ul><ul><ul><li>subendocardial infarction - non Q wave </li></ul></ul><ul><li>Location of wall </li></ul><ul><ul><li>anterior,posterior, lateral, anterolateral, inferior, septal </li></ul></ul><ul><ul><li>Location by ECG (Table 29.1 pg 420) </li></ul></ul>
  45. 56. Acute Myocardial Infarction <ul><li>Location of obstructive lesion </li></ul><ul><ul><li>determines wall(s) affected </li></ul></ul><ul><ul><li>proximal vs. distal occlusion </li></ul></ul>
  46. 59. Diagnosis of Acute MI <ul><li>Symptoms </li></ul><ul><li>ECG </li></ul><ul><ul><li>figure 27.4 Resource Manual </li></ul></ul><ul><li>evaluation of cardiac enzymes </li></ul><ul><ul><li>page 235 Resource Manual </li></ul></ul><ul><ul><li>lactate dehydrogenase (LDH) </li></ul></ul><ul><ul><li>Creatinine phosphokinase (CK) </li></ul></ul><ul><ul><ul><li>CK-MB elevated in first 24 hrs </li></ul></ul></ul>
  47. 61. Treatment of MI <ul><li>Early reperfusion </li></ul><ul><ul><li>streptokinase or tissue plasminogen activator (tpa) </li></ul></ul><ul><ul><li>“ rescue” angioplasty </li></ul></ul><ul><ul><li>emergent CABS </li></ul></ul><ul><li>nitroglycerine </li></ul><ul><li>beta blockers </li></ul>
  48. 62. Post-Myocardial Infarction <ul><li>Necrosis, scarring during first 6-12 weeks </li></ul><ul><li>Infarct dilation and remolding - thinning of ventricular wall and enlargement of cardiac chambers </li></ul><ul><li>may develop congestive heart failure </li></ul>
  49. 63. Myocardial Infarction <ul><li>Characteristics associated with higher risk of reinfarction and death </li></ul><ul><ul><li>EF<40% </li></ul></ul><ul><ul><li>ischemia during low intensity exercise </li></ul></ul><ul><ul><li>poor exercise capacity (<4 METS) </li></ul></ul><ul><ul><li>complex ventricular arrhythmias </li></ul></ul>