Lecture Slides: Alterations of CV Function II PDF

NURS 7053 ALTERATIONS OF CV FUNCTION II Myocardial Ischemia, Myocardial Infarction  LEARNING OUTCOMES By the end of this lecture, learners will be able to: 1. Explain the pathophysiology of myocardial ischemia and myocardial infarction. 2. Analyze the relationship between cardio...

NURS 7053 ALTERATIONS OF CV FUNCTION II Myocardial Ischemia, Myocardial Infarction  LEARNING OUTCOMES By the end of this lecture, learners will be able to: 1. Explain the pathophysiology of myocardial ischemia and myocardial infarction. 2. Analyze the relationship between cardiovascular physiology and the development of myocardial ischemia and infarction. 3. Differentiate between the various causes of myocardial ischemia and myocardial infarction. 4. Predict the clinical manifestations of myocardial ischemia and infarction based on their underlying pathophysiology.  Section 1 MYOCARDIAL ISCHEMIA  OVERVIEW Partial blockage of one or more branches of the left or right coronary artery Coronary arteries  CAUSES Coronary atherosclerosis (coronary artery disease) – The vast majority of cases of myocardial ischemia are caused by atherosclerosis in the coronary arteries. This condition is often called coronary artery disease (CAD). Risk factors for CAD are the same as most of the general risk factors for atherosclerosis and include smoking, diabetes mellitus, and dyslipidemia.  OTHER CAUSES OF ISCHEMIA Vasospasm of coronary arteries – There are vasoconstrictive mediators released during the development of atherosclerosis that may contribute to vasospasms of the coronary artery. – Vasospasm tends to cause transient ischemia and associate symptoms.  OTHER FACTORS Hypoxemia – Often from pulmonary disease and the resulting decrease in gas exchange in the lungs. O2 Hypoxemia  OTHER FACTORS Anemia Anemia  OTHER FACTORS Increased Myocardial Demand/Workload – Tachycardia (increased heart rate) and/or increased cardiac output is an example of a condition where myocardial demand can outstrip the delivery of O2 to the myocardium. Sinus tachycardia on an electrocardiogram LEARNING ACTIVITY I  PATHOPHYSIOLOGY Coronary atherosclerosis results in myocardial ischemia – When atherosclerotic plaque builds up in the coronary arteries, not only is the lumen size of the vessel decreased, it is unable to relax and vasodilate. O2 demand > O2 supply – If the heart muscle cannot get enough oxygen, it cannot make enough ATP to maintain its normal cellular activities.  CLINICAL CONSEQUENCES Consequences of Myocardial Cell Hypoxia Decreased Ventricular Pumping Conduction Disturbances  CLINICAL CONSEQUENCES Ischemic Pain - Stable Angina Pectoris Intermittent chest pain occurring with the same pattern of onset, duration and intensity Stable Angina – Lasts for a few minutes – Relieved by rest, position change or when precipitating factor has stopped (activity, stress, etc.), and/or nitroglycerin. – Pain is often described as a tightness, pressure, squeezing, or heartburn – Pain can radiate (arms, shoulders, jaw).  CLINICAL CONSEQUENCES Ischemic Pain - Unstable Angina Pectoris Chest pain lasting 15 to 20 minutes not relieved by rest, position change or nitroglycerin – Often described as crushing, pressure, tightness Unstable Angina or burning – Pain often radiates (arms, shoulders, jaw) – Sign of impending myocardial infarction  Section 2 MYOCARDIAL INFARCTION  TYPES Classification Description of Categories Morphologic Transmural: necrosis extends throughout the entire wall of the myocardium Non-transmural: necrosis is limited to the endocardium or subendocardium (most frequent), or a segment of the myocardium. STEMI vs. NSTEMI STEMI: MI in the presence of ST segment elevation on the ECG NSTEMI: no ST segment elevation Fourth Universal Myocardial Injury: Elevated troponin with at least one value > 99 %ile Definition of Myocardial Type 1: MI related to acute athero-thrombosis of artery feeding the Infarction (2018) infarcted myocardium Type 2: Supply-demand mismatch unrelated to acute athero-thrombosis Type 3: Cardiac death in patients with symptoms suggestive of myocardial ischemia and presumed new ischemic EKG changes before troponin levels available or abnormal Type 4a: MI associated with percutaneous coronary intervention Type 4b: MI related to stent thrombosis Type 4c: MI related to restenosis Type 5: MI related to CABG Don’t memorize!  CAUSES Coronary atherosclerosis (coronary artery disease)  CAUSES Other causes include: – Coronary artery emboli – Aortic dissection with retrograde involvement of the coronary arteries – Coronary vasospasm – Coronary artery trauma – Cocaine and other illicit drug use – Rx & OTC drugs Coronary artery  CAUSES Precipitating conditions include factors that increase metabolic demand: – Extreme physical demand – Hypertension – Aortic stenosis HTN causes an ⬆ in LV afterload Aortic stenosis caused by atherosclerosis of the aortic valve leaflets  CAUSES Precipitating conditions also include factors reduce the oxygen content of the blood: – Hypoxemia (altitude, pulmonary disease) – Anemia  PATHOPHYSIOLOGY Infarction of an atherosclerotic coronary artery occurs due to the following circumstances: – Thrombus forms on the rough surface of the plaque – Wall of an atherosclerotic coronary artery ruptures – Long term obstruction of coronary artery by plaque – Plaque embolus obstructs coronary artery Fig. 33-20 A Page 1083  PATHOPHYSIOLOGY Fig. 33-19 Page 1083 Pathogenesis of an unstable plaque and thrombus formation leading to MI.  PATHOPHYSIOLOGY Hypoxic injury – Within 10 second of infarct there is hypoxic injury to the myocardial cells – Without adequate oxygen, the myocardial cells switch to anaerobic metabolism – Decrease O2 availability  decreased ATP production & lactic acid formation Review - Other consequences of hypoxic injury include: Failure of Na+-K + pump leading to cellular swelling Failure of the Ca2+ pump leading Ca2+ accumulation & mitochondrial injury Release of lysosomal enzmes leading to autodigestion  PATHOPHYSIOLOGY Hypoxic injury (continued) – After 20 minutes without oxygen, the infarcted myocardial cells are irreversibly injured and die. Unlike many other tissues, cardiac muscle tissue cannot regenerate. Myocardial infarction Arrows are pointing to infarcted areas where the muscle tissue has become necrotic.  PATHOPHYSIOLOGY Inflammation – Neutrophils release a myriad of inflammatory mediators, some of which can cause myocardial cell injury (e.g., NO, IL-1, TNF, etc…). – Neutrophils release reactive oxygen species (ROS) and lysosomal enzymes during phagocytosis, which further contribute to myocardial cell injury.  REPERFUSION INJURY Definition: Restoration of blood flow to ischemic tissue can paradoxically cause additional injury Oxidative Stress Calcium Overload Inflammation Appears within minutes Initial ischemic Neutrophil ROS formation: OH-, accumulation adhesion O2-, ONOO-, H202 Additional influx during Cytokine release Damages membrane reperfusion Protease damage proteins and lipids Mitochondrial damage Oxidant release Decrease ATP production REPERFUSION INJURY REPERFUSION INJURY  PATHOPHYSIOLOGY Repair and resolution  LEARNING ACTIVITY II 10-20 MINUTES 10 SECONDS REPAIR AND RESOLUTION IRREVERSIBLE INJURY INFLAMMATORY CASCADE REPERFUSION INJURY TIME 0  CLINICAL CONSEQUENCES Functional impairment depends on size of infarct Decreased Ventricular Contractility Ischemic Pain Conduction Disturbances LEARNING ACTIVITY III  CARDIAC BIOMARKERS Troponin I & T – Troponin T is found in cardiac and skeletal muscle, but it is possible to tell the difference between the two forms. – Troponin I is only found in cardiac muscle. Elevated (positive) troponin levels (cardiac TnI and TnT via immunoassay) are considered diagnostic of an acute MI/  CARDIAC BIOMARKERS Troponin I & T (continued) – Troponin levels start to rise 2-3 hours after the infarct and peak at 12-48 hours. Levels remain elevated for 4-10 days. Note: Focus on the physiology & pathophysiology underlying the different laboratory alterations, rather than memorizing the timing or actual levels.  CARDIAC BIOMARKERS CK-MB – CK enzymes exist in a variety of forms known as isoenymes. The isoenyme found primarily in cardiac muscle is CK-MB (a.k.a. CPK- 2). A rise in the CK-MB is indicative of AMI or unstable angina. – In most cases, assays of CK and CK-MB are obtained so that the ratio of CK-MB to CK can be evaluated. If CK-MB: CK ratio > 5, AMI should be suspected.  CARDIAC BIOMARKERS CK-MB (continued) – CK-MB levels start to rise 4-6 hours following an AMI, peak at 24 hours, and return to normal after 2-3 days.  CARDIAC BIOMARKERS Myoglobin – Myoglobin is an intracellular protein similar to hemoglobin that is present in all muscle cells. Myoglobin is released when muscle cells are injured or die. – Rises in myoglobin occur very rapidly following an AMI and the lab test is very sensitive. However, this test is not very specific because other cells contain myoglobin.  CARDIAC BIOMARKERS C-reactive protein (CRP) – CRP is a plasma protein that the liver releases during an inflammatory response. – CRP will become elevated following an ischemic event. Studies have found elevated CRP to be a reliable predictor of degree of heart failure and mortality following an AMI. Note: CRP is also used to predict cardiovascular risk and risk of death from cardiovascular disease CRP Levels Risk of Cardiovascular Disease < 1.0 mg/L Low risk 1.0-2.9 mg/L Intermediate risk > 3.0 mg/L High risk  CARDIAC BIOMARKERS Lactate dehydrogenase (LDH) – LDH-1 is an isoenzyme of LDH that is primarily found in cardiac muscle cells. – LDH-2 is the isoenzyme primarily found in the plasma. – An elevation of LDH-1 (or an increase in the ratio of LDH-1 to LDH- 2) is indicative of myocardial cell injury. LDH isoenzyme Location Note: An isoenzyme is a different form of an enzyme that catalyzes the LDH-1 Cardiac muscle, RBCs same chemical reaction. LDH-2 WBCs, plasma LDH-3 Lungs LDH-4 Kidneys, pancreas LDH-5 Liver, skeletal muscle  CARDIAC BIOMARKERS Lactate dehydrogenase (LDH) (continued) – The sensitivity of LDH in the diagnosis of AMI is high (~98%), but the specificity is low (false positive rate of 30%). – LDH levels begin to rise 24-72 hours following the AMI, peak at 3-4 days, and return to normal in 8-14 days.  OTHER LABS Glucose CBC Chemistry profile Lipid profile LEARNING ACTIVITY IV What cellular processes are occurring right now? Which biomarkers would you expect to be elevated at this point? What immediate interventions are most crucial? What complications should you anticipate during the healing process?