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Cardiovascular pathology coronary heart disease finale


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Prepared by md, PhD. Marta R. Gerasymchuk, pathophysiology department of IFNMU

Published in: Health & Medicine

Cardiovascular pathology coronary heart disease finale

  1. 1. CONTENT1. Features of coronal circulation of blood and metabolism of cardiac muscle.2. Classification of coronary heart disease. CHD: determination, reasons and terms of origin, form.3. Ischemic heart disease. Definition of the notion, risk factors, mechanisms of development4. Sudden coronary death: reasons, mechanisms of origin.5. Angina pectoris: classification, pathogenesis of displays.6. Heart attack of myocardium: kinds, description of functional and biochemical violations in a cardiac muscle, mechanisms of pain syndrome.7. Mechanisms of origin of spasms of coronary vessels.8. Complication of heart attack of myocardium. Pathogenesis of cardiogenic shock.9. Experimental models of heart attack of myocardium.
  2. 2. ACTUALITY• The term coronary heart disease (CHD) describes heart disease caused by impaired coronary blood flow. In most cases, CHD is caused by atherosclerosis.• Diseases of the coronary arteries can cause angina, angina myocardial infarction or heart attack, cardiac attack dysrhythmias, conduction defects, heart failure, and dysrhythmias defects failure sudden death. death• During the past 50 years, there have been phenomenal advances in understanding the pathogenesis of CHD and in the development of diagnostic techniques and treatment methods for disease.• However, declines in morbidity and mortality have failed to keep pace with these scientific advances, probably because many of the outcomes are more dependent on lifestyle factors and age than on scientific advances. advances
  3. 3. FUNCTIONAL ORGANIZATION OF THE CIRCULATORY SYSTEM■ The circulatory system consists of the heart, heart which pumps blood; the arterial system, system which distributes oxygenated blood to the tissues; the venous system, which collects system deoxygenated blood from the tissues and returns it to the heart; and the capillaries, capillaries where exchange of gases, nutrients, and wastes occurs.■ The circulatory system is divided into two parts: the low-pressure pulmonary circulation, linking the transport function of circulation the circulation with the gas exchange function of the lungs; and the high-pressure systemic circulation, providing oxygen and circulation nutrients to the tissues.■ The circulation is a closed system, so the output of the right and left heart must be equal over time for effective functioning of the circulation.
  4. 4. Coronary Heart Disease The term coronary heart disease (CHD) describes heart disease caused by impaired coronary blood flow. In most cases, CHD is caused by atherosclerosis. Diseases of the coronary arteries can cause angina, myocardial infarction or heart attack, cardiac dysrhythmias, conduction defects, heart failure, and sudden death. Heart attack is the largest killer of American men and women, claiming more than 218,000 lives annually. Each year, 1.5 million Americans have new or recurrent heart attacks, and one third of those die within the first hour, usually as the result of cardiac arrest resulting from ventricular fibrillation.
  5. 5. Pathogenesis of Coronary Heart Disease • HDL (good) cholesterol removes excess cholesterol in the blood stream. • LDL (bad) cholesterol enters the arterial wall and is taken up by our body’s scavenger cells. • Subsequently, they will turn into fatty streaks which progress into atheromatous plaques. • Hence, LDL cholesterol is said to promote atherosclerosis.
  6. 6. Healthy LifestyleWell-Balanced Cholesterol Levels :•Cholesterol readings includes: Total cholesterol Desirable : < 5.2 mmol/L Borderline High : 5.2 – 6.2 mmol/L High : ≥ 6.2 mmol/L LDL cholesterol Desirable : < 3.3 mmol/L Borderline High : 3.3 – 4.1 mmol/L High : ≥ 4.1 mmol/L
  7. 7. Healthy LifestyleWell-Balanced Cholesterol Levels : HDL cholesterol Acceptable: ≥ 0.9 mmol/L Risky : < 0.9 mmol/L Triglyceride Desirable : < 2.3 mmol/L•A healthy person should have a higher level ofHDL and a low level of LDL and triglyceride .
  8. 8. Types of chronic ischemic heart disease and acute coronary syndromes Coronary heart diseaseChronic ischemic heart disease Acute coronary syndrome Stable Variant No ST-segment ST-segment angina angina elevation elevation Silent myocardial Unstable Q-wave ischemia angina AMI Non-ST-segment elevation AMI
  9. 9. The Normal Heart - Coronary Artery Anatomy Left Main CA Layers of the Arterial Wall Circumflex Adventitia Media Intima Right CALeft Anterior Descending CA Marginal Branch Intima composed of endothelial cells
  10. 10. Atherosclerosis: A Progressive Process Plaque Ischemia Occlusive Rupture/ Unstable Fibrous Fissure & Fatty Atherosclerotic Thrombosis Angina Normal Streak Plaque Plaque Thrombus formation MI Coronary vasospasm Coronary Death StrokePHASE I: Initiation PHASE II: Progression PHASE III: Complication Critical Leg Ischemia Disease progression Libby P. Circulation. 2001;104:365-372.
  11. 11. Complicated Fibrous Lesion/ Plaque Intermediate Rupture Atheroma Lesion Fatty Foam Streak Cells Pathogenesis of Atherosclerosis
  12. 12. 1) FATTY STREAK (non- palpable, but a visible YELLOW streak)2) ATHEROMA (plaque) (palpable)3) THROMBUS (non- functional, symptomati c)
  13. 13. Coronary Artery Pathology in Ischemic Heart Disease PlaqueSyndrome Stenoses Disruption Plaque-Associated ThrombusStable angina >75% No NoUnstable angina Variable Frequent Nonocclusive, often with thromboemboliTransmural Variable Frequent Occlusivemyocardial infarctionSubendocardial Variable Variable Widely variable, may be absent,myocardial infarction partial/complete, or lysed FrequentSudden death Usually Often small platelet aggregates or thrombi severe and/or thromboemboli
  14. 14. The IVUS technique can detect angiographically ‘silent’ atheroma IVUSAngiogram LittleNo evidence evidence ofof disease disease anterior descending Atheroma coronary artery IVUS=intravascular ultrasound Nissen S, Yock P. Circulation 2001; 103: 604–616 IVUS – intravascular ultrasaund
  15. 15. Correlation of CT angiography of thecoronary arteries with intravascular Non-calcified, soft, lipid-rich plaque inultrasound illustrates the ability of MDCT left anterior descending artery (arrow) .to demonstrate calcified and non-calcified The plaque was confirmed bycoronary plaques (Becker et al., Eur J intravascular ultrasound (Kopp et al.,Radiol 2000) Radiology 2004)
  16. 16. Pathophysiology of ISCHEMIA Ischemia of cardiac cells occurs when the oxygen supply is insufficient to meet metabolic demands. Myocardial cells are unable to store much energy in the form of adenosine triphosphate (ATP) and must therefore continuously receive a supply of oxygen for aerobic synthesis of ATP. ATP is essential for powering myocardial construction as well as for cell maintenance. Because the heart is unable to slow its activity when ATP supplies dwindle, it is essential that a steady flow of oxygen be provided.
  17. 17. Critical factors in meeting cellular demands for oxygen are: the rate of coronary perfusion the myocardial workload can be impaired in next ways depends on Large, stable Vasospasm Heart rateatherosclerotic plaque PreloadAcute platelet aggregation Poor perfusion and thrombosis pressure AfterloadFailure of autoregulation Contractility by the microcirculation
  18. 18. ANGINA PECTORIS• Par oxysmal (sudden)• Recur r ent• 15 sec.15 min.• Reduced perfusion, but NO infar ction• THREE TYPES • STABLE: relieved by rest or nitroglycerin • PRINZMETAL: SPASM is main feature, responds to nitro, S-T elevation • UNSTABLE (crescendo, PRE-infarction, Q-wave angina): perhaps some thrombosis, perhaps some non transmural necrosis, perhaps some embolization, but DISRUPTION of PLAQUE is universally agreed upon
  19. 19. Chest Pain First symptom of those suffering myocardial ischemia. Called angina pectoris (angina – “pain”) Feeling of heaviness, pressure Moderate to severe In substernal area Often mistaken for indigestion May radiate to neck, jaw, left arm/ shoulderDue to : Accumulation of lactic acid in myocytes or stretching of myocytes
  20. 20. Stable angina pectoris Caused by chronic coronary obstruction Recurrent predictable chest pain Gradual narrowing and hardening of vessels so that they cannot dilate in response to increased demand of physical exertion or emotional stress Lasts approx. 3-5 minutes Relieved by rest and nitrates Stress test shows ST segment depression > 1mm
  21. 21. Prinzmetal angina pectoris (Variant angina) Caused by abnormal vasospasm of normal vessels (15%) or near atherosclerotic narrowing (85%) Occurs unpredictably and almost exclusively at rest. Often occurs at night during REM sleep (rapid eye movement) May result from hyperactivity of sympathetic nervous system, increased calcium flux in muscle or impaired production of prostaglandin Vasoconstriction is due to platelet thromboxane A2 or an increase in endothelin This causes a pattern of ST elevation that is very similar to acute STEMI — i.e. localised ST elevation with reciprocal ST depression occurring during episodes of chest pain. However, unlike acute STEMI the ECG changes are transient, reversible with vasodilators and not usually associated with myocardial necrosis. They may be impossible to differentiate on the ECG. ST elevation myocardial infarction (STEMI)
  22. 22. Silent Ischemia Totally asymptomatic May be due abnormality in innervation Or due to lower level of inflammatory cytokines
  23. 23. Treatment Pharmacologically manipulate blood pressure, heart rate, and contractility to decrease oxygen demands Nitrates dilate peripheral blood vessels and  Decrease oxygen demand  Increase oxygen supply  Relieve coronary spasm
  24. 24.   blockers:  Block sympathetic input, so  Decrease heart rate, so  Decrease oxygen demand Digitalis  Increases the force of contraction Calcium channel blockers Antiplatelet agents (aspirin, etc.)
  25. 25. Surgical treatment• Angioplasty – mechanical opening of vessels• Revascularization – bypass • Replace or shut around occluded vessels
  26. 26. ACUTE CORONARY SYNDROMES “The acute coronary syndromes are frequently initiated by an unpredictable and abrupt conversion of a stable atherosclerotic plaque to an unstable and potentially life- threatening atherothrombotic lesion through superficial erosion, ulceration, fissuring, rupture, or deep hemorrhage, usually with superimposed thrombosis.”
  27. 27. Unstable Angina pectoris Lasts more than 20 minutes at rest, or rapid worsening of a pre-existing angina May indicate a progression to M.I.Pathogenesis: Severe, fixed, multivessel atherosclerotic disease Disrupted plaques with or without platelet nonocclusive thrombi
  28. 28. The ECG above belongs to a patient with unstable angina pectoris. Negative T pectoriswaves are observed in leads C2-C5 while negative U waves are seen in leads C2-C4. Additionally, the PR interval is above 200 msec (1st degree AV block).Coronary angiography showed significant stenosis of the LAD and Circumflex(Cx) arteries
  29. 29. Sudden cardiac death (SCD) 1. Inexpected death within 1 hour after the onset of symptoms2. Risk factors a. Obesity b. Glucose intolerance c. Hypertension d. Recent non-Q wave myocardial infarction e. Smoking3. Occurs more frequently in the morning hours when hypercoagiilability is at its peack4. Pathogenesis a. Severe atheroselerotic coronary artery disease b. Disrupted filimns plaques c. Absence of occlusive vessel thrombus (>80%; of cases) d. Cause of death is ventricular fibrillation. 5. Diagnosis of exclusion after the following causes are ruled out a. Mitral valve prolapse (MVP) b. Hypertrophic cardiomyopathy c. Calcific aortic stenosis d. Conduction system abnormalities e. Cocaine abuse
  30. 30. Acute myocardial infarction (AMI)1. Epidemiology a. Most common cause of death in adults in the United States. b. Prominent in males between 40 and 65 years old c. No predominant sex predilection after 65 years old d. At least 25% of AMIs are clinically unrecognized.
  31. 31. Myocar dial Ischemia Myocardial cell metabolic demands not met Time frame of coronary blockage:  10 seconds following coronary block  Decreased strength of contractions  Abnormal hemodynamics  See a shift in metabolism, so within minutes:  Anaerobic metabolism takes over  Get build-up of lactic acid, which is toxic within the cell  Electrolyte imbalances  Loss of contractibility
  32. 32. 20 minutes after blockage Myocytes are still viable, so If blood flow is restored, and increased aerobic metabolism, and cell repair,  →Increased contractilityAbout 30-45 minutes after blockage, if no relief Cardiac infarct & cell death
  33. 33. Myocardial infarction Necrosis of cardiac myocytes – Irreversible – Commonly affects left ventricle – Follows after more than 20 minutes of ischemia
  34. 34. Pathogenesisa. Sequence 1) Sudden disniptinn of an atheromatous plaque 2) Subendothelial coliagen and thrombogenic necrotic material are exposed. 3) Platelets adhere to the exposed material and eventually form an occlusive platelet thrombus.b. Role of thromboxane A2 1) Contributes to formation of the platelet thrombus 2) Causes vasospasm of the artery to reduce blood flow
  35. 35. PATHOPHYSIOLOGY Coronary artery cannot supply enough blood to the heart in response to the demand due to CAD Within 10 seconds myocardial cells experience ischemia Ischemic cells cannot get enough oxygen or glucoseMyocardium Infarction Ischemic myocardial cells may have decreased electrical & muscular function Cells convert to anaerobic metabolism. Cells produce lactic acid as waste Pain develops from lactic acid accumulation Pt feels anginal symptoms until receiving demand increase 02 requirements of myocardial cells
  36. 36. PROGRESSION OFNECROSIS 0-1/2 hr reversible injury
  37. 37. Types of myocardial infarctiona. Transmural infarction (Qwave infarction)• 1) Involves the full thickness of the myocardium• 2) New Q waves develop in an electrocardiogram (ECG).b. Subendocardial infarction (non-Q wave infarction)• 1) Involves the inner third of the myocardium• 2) Q waves are absent.
  38. 38. Reperfusion injury a. Follows thrombolytic (fibrinolytic) therapy b. Early reperfusion salvages some injured but viable myocytes but destroys myocytes that are irreversibly damaged.1) Removal of irreversibly damaged myocytes improves short- and long-term function and survival.2) Prevents any further damage to myocardial cells3) Limits the size of the infarction c. Reperfusion histologically alters irreversibly damaged cells.1) Produces contraction band necrosis2) Caused by hyporcontraction of myofibrils in dying cells • Due to the influx of Ca-++ into the cytosol
  39. 39. RE-PERFUSION  Thrombolysis  PTCA  CABG  Reperfusion CANNOT restore necrotic or dead fibers, only reversibly injured ones  REPERFUSION “INJURY”  Free radicals  Interleukins
  40. 40. Consequences after acute coronary artery occlusionBlood flow M. Ischemia Chest discomfort PMVT, VF M.stunning Heart failure STEMI NSTEMI ,UA Sudden Cardiogenic Elevated Death shock +CK,Trop-T Cardiovascular Research & Prevention Center, Bhumibol Adulyadej hospital
  41. 41.  May hear extra, rapid Clinical Manifestations heart sounds ECG changes:  T wave inversion  ST segment depression
  42. 42. MYOCARDIAL INFARCTIONTransmural vs. Subendocardial (inner 1/3)DUH! EXACT SAME risk factors as atherosclerosisMost are TRANSMURAL, and MOST are caused bycoronary artery occlusionIn the 10% of transmural MIs NOT associated withatherosclerosis:  Vasospasm  Emboli  UNexplained
  43. 43. Structural, functional changes Decreased contractility Decreased LV compliance Decreased stroke volume Dysrhythmias Inflammatory response is severe Scarring results –  Strong, but stiff; can’t contract like healthy cells
  44. 44. Sign and Symptom Classic symptom of heart attack are chest pain radiating to neck, jaws, back of shoulder, or left arm The pain can be felt like: Squeezing or heavy pressure A tight band on the chest An elephant sitting on the chest
  45. 45. Other symptoms Cont include: Shortness of breath (SOB) Weakness and tiredness Anxiety Lightheadedness Dizziness Nausea vomiting Sweating, which may be profuse
  46. 46. Clinical manifestations Sudden, severe chest pain  Similar to pain with ischemia, but stronger  Not relieved by nitrates  Radiates to neck, jaw, shoulder, left arm Indigestion, nausea, vomiting Fatigue, weakness, anxiety, restlessness and feelings of impending doom. Abnormal heart sounds possible (S3,S4)
  47. 47.  Blood test show several markers:  Leukocytosis  Increased blood sugar  Increased plasma enzymes  Creatine kinase  Lactic dehydrogenase  Aspartate aminotransferase (AST or SGOT)  Cardiac-specific troponin
  48. 48. Laboratory diagnosis of AMI I. Serial testing for creatine kinase isoenzyme MB (CK-MB)1) CK-MB appears within 4 to 8 hours; peaks at 24 hours; disappears within 1.5 to 3 days. • Sensitivity and specificity 95%,2) Reinfarction a) Occurs in 10% of AMIs b) Reappearance of CK-MB after 3 days II. Serial testing for cardiac troponins I (cTnl) and T (cTnT)1) Normally regulate calcium-mediated contraction2) cTnl and cTnT appear within 3 to 12 hours: peak at 24 hours; disappear within 7 to 10 days. a) Sensitivity 84% to 96%, specificity 80% to 95% b) False positive results are lisually related to ischemia (e.g., unstable angina),3) CK-MB is used in conjunction with troponins to diagnose an AMI. a) Detects reinfarction (troponins cannot) b) Improves overall sensitivity and specificiry in diagnosing an AMI III. Lactate dehydrogenase (LDH)1-2 "flip"1) Normally, LDH2 is higher than LDH1. • In AMI, LDH1 in cardiac muscle is released, causing the “flip,"2) LDH1-2 • Appears within 10 hours; peaks at 2 to 3 days: disappears within 7 days3) This test has been replaced by troponins I and T.
  49. 49. Treatment First 24 hours crucial Hospitalization, bed rest ECG monitoring for arrhythmias Pain relief (morphine, nitroglycerin) Thrombolytics to break down clots Administer oxygen Revascularization interventions: by- pass grafts, stents or balloon angioplasty
  50. 50. AMI DIAGNOSIS• SYMPTOMS• EKG• DIAPHORESIS• (10% of MIs are “SILENT” with Q-waves)• CKMB gold standard enzyme• Troponin-I, Troponin-T better• CRP predicts risk of AMI in angina patients
  51. 51. Primary Management Techniques• Heart Attack Treatment• First you must conduct a primary survey of the casualty;• A primary survey consists of following the DRABCD procedure, this involves; • D = DANGER – If I find a heart attack casualty I should check for any surrounding danger to myself first and for the casualty and others • R = Response – I should asses whether the person is conscious or unconscious using the COWS procedure; -Can you hear me, -Open your eyes, -What is your name, -Squeeze my hand. • A = Airways - After response if the casualty is unconscious I should then check the airways for any obstructions or blockages and if there is a blockage turn the victim onto his/her side and clear the airway. • B = Breathing – The next step if the patient is unconscious is to check for signs of life. Check for breathing by using look, listen and feel technique. If breathing place the casualty in recovery position, if not give 2 rescue breaths and... • C = Compressions - If the casualty is unconscious with no breathing, start compressions immediately! Give 30 compressions. At a rate of 100 compressions per minute (approx 2 compressions per second). At 1/3 depth of the casualty’s chest. • D = Defibrillation - If available use a defibrillator on the casualty as soon as possible.
  52. 52. Definitions• Cardiac Output: (Q) = HR X SV• Cardiac Index = Q / body surface area• Preload: (EDV) volume of the left ventricle at the end of diastole (dependent on venous return & stretch of the cardiac muscle cells)• Afterload: resistance to ventricular emptying during systole (the amount of pressure the left ventricle must generate to squeeze blood into the aorta)• Frank Starling Law of the Heart:the heart will contract with greater force when preload (EDV) is increased• Myocardial Contractility: the squeezing contractile force that theheart can develop at a given preload • regulated by: • sympathetic nerve activity (most influential) • catecholamines (epinephrine norepinephrine) • amount of contractile mass • drugs
  53. 53. Don’t wait for a heart attack to take an action ! Don’t wait for a second life we are not cats!
  54. 54. References1. General and clinical pathophysiology / Edited by Anatoliy V. Kubyshkin – Vinnytsia: Nova Knuha Publishers – 2011. – P.460–478.2. Russell J. Greene. Pathology and Therapeutics for Pharmacists. A basis for clinical pharmacy practice / Russell J. Greene, Norman D. Harris // Published by the Pharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, London SE1 7JN, UK 100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820, 3rd edition, USA. – 2008. – Chapter 4. – P. 166–207, 235–269 .3. Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams & Wilkins), Trade paperback (2003) / Carol Mattson Porth, Kathryn J. Gaspard. – Chapters 14, 17, 18. – P. 231–303, 308–338.4. Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine Publishing. – 2010. – P. 344–351.5. Gozhenko A.I. General and clinical pathophysiology / A.I. Gozhenko, I.P. Gurcalova // Study guide for medical students and practitioners. Edited by prof.Zaporozan, OSMU. – Odessa. – 2005.– P. 207–221.6. Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme. Stuttgart. New York. – 2000. – P. 194–205, 216–233.7. Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition. Copyright В. – Lippincott Williams & Wilkins – 2008. – Chapter 13. – P. 292–298, 345–347, 414–429, 447–462.8. Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L. Banasic // Elsevier Inc. – 2010. – P. 396–427, 448–509.9. Robbins and Cotran Pathologic Basis of Disease 8th edition./ Kumar, Abbas, Fauto. – 2007. – Chapter 11. – P. 379–398, 400–420.10. Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth, Glenn Matfin. – New York, Milwaukee. – 2009. – P. 536–553, 584–633.
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