Myocardial Infarction: From Ischaemia to Necrosis - Essay Example

Myocardial Infarction: From Ischaemia to Necrosis Name ID: Course Institutional Affiliation Instructor Date Abstract The aim of the paper is to discuss pathogenesis of myocardial infarction from ischaemia to necrosis. Secondary data relevant to myocardial infarction was generated from peer-reviewed articles published in PubMed. Findings are presented as responses to discussion questions. In the discussion, Ischaemia is defined as a restriction of blood flow in the heart tissues because of events such as arteriosclerosis, thromboembolism and trauma. Mechanisms by which ischaemia can cause injury, include cardio-protective mechanisms such as inflammatory responses, nitrogen-oxide cycles and glycolysis, and ATP pathway. Ischaemia can be treated by reperfusion if the cell injury is reversible. Irreversible cell injury due to persistent ischaemia results to cell death by necrosis or apoptosis. Coagulative necrotic patterns are visible during histological analysis. Autopsy after many days reveal collageneous tissue, in which the cells nuclei and striations are lost. Major biomarkers of myocardial infarction in laboratory investigations include cardiac troponins and creatinine kinase. 1. Introduction Myocardial infarction, commonly known as heart attack is a significant epidemiological statistics in today’s society. Causes vary from lifestyle, associated diseases, and genetics among others (Jneid et al. 2013). The pathogenesis of myocardial infarction is preventive if controlled at the early stages is ischaemia. Adjustments to lifestyle changes, observance of safety measures and pharmocotherapy can help reduce mortality rates associated with myocardiac infarction (Marchant et al. 2012). This report discusses ischaemia in the heart muscle and the events that causes it, mechanisms of injury, sequential progression from reversible cell injury to irreversible cell death, pattern of tissue necrosis and associated histological findings at autopsy, and the major biomarkers in laboratory investigation of myocardial infarction. 2. General Discussion a. Definition of Ischaemia and the Outline of Events which Lead to Ischaemia in Heart Muscle Ischaemia is a condition that occurs when blood supply to body tissues is restricted because the arteries feeding the tissues or organ are blocked (Fleischmann et al. 2011). In ischaemia of the heart muscle, the tissues are progressively or suddenly depleted of oxygen and other nutrients required for cell metabolism. Events which lead to ischemia in heart muscle include atherosclerosis, occlusion by thromboembolism and/or traumatic injury (Lyaker et al. 2013). Atherosclerosis occurs as plaque from accumulated cholesterol in the arteries that block the blood flow and cause the arterial walls to thicken and harden. Other deposited materials include white blood cells which invade the inflamed areas, and calcium and crystallised materials (Lyaker et al., 2013). The stiffening of the wall can increase pulse pressure resulting to palpitations and arrhythmia, chest pains and dizziness. The blood flow can also be blocked by a thrombus or blood clot. The clot leads to pulmonary embolus, where occlusion of oxygen from the arteries involved occurs and blood supply to the organ decreases suddenly (Lyaker et al. 2013). Blood vessels can partially or entirely be occluded of oxygen because of traumatic injury from shearing, laceration or compression of blood vessels. Traumatic injury may follow events such as arterial dissection in the aorta after angiography or any medical procedures and reactions from the patients (Lyaker et al. 2013). b. The Mechanisms by which Ischaemia Causes Injury When ischaemia occurs, it triggers oxidative stress, cellular damage and cytokine release which activate neutrophil mobilization to the affected area (Marchant et al. 2012). Mechanisms responsible for causing injury include cellular calcium overload, oxygen/nitrogen reactions which promote mitochondrial permeability transition pore during cell death. During ischemiac injury the heart muscle displays a powerful inflammatory response that contributes to tissue injury (Marchant et al. 2012). The inflammation is because of neutrophil/white blood cell accumulation in the affected area. Furthermore, cardioprotective activities of ischaemic pre and post conditioning have made it possible to identify a complex network of signalling pathways which finally close in on the mitochondria to impart cytoprotection (Mozaffari et al. 2013). A reduction in the energy produced by the mitochondria leads to decreased intercellular pH because of increased lactic acid produced from anaerobic glycolysis as oxygen supply is reduced. The lowered pH also disrupts the ionic homeostasis and causes the subsequent overload of calcium ions (Mozaffari et al. 2013). The sarcolemmal sodium and hydrogen ion exchange is activated as the cells attempts to balance the pH. However, the process is inefficient because of a decrease in mitochondrial energy production (Perrelli, Pagliaro & Penna 2011). Anaerobic energy provision stalls after the glycolytic substrates are exhausted, or the glycolytic function is inhibited by metabolite accumulation that would have been otherwise removed if the blood flow was unobstructed. c. The Sequential Progression from Reversible Cell Injury to Cell Death in Myocardial Infarction Healthy cells are capable of maintaining the optimum homeostasis requirement. If they encounter pathologic stimuli and physiologic stress, they undergo hypertrophy, an adaptation mechanism to obtain a new steady state that will enable them to preserve their viability and function (O’Neal et al. 2012). Ischaemic cellular pathology begins with structural and molecular alterations in cells. The cells’ adaptive capability is exceeded or the cells are injured because of stress brought by the mechanisms leading to cell injury in ischaemia. Although cell injury is harmful, within certain limits a reversible state can be achieved. The cells return to a stable baseline. The injury is amenable to repair depending with the duration of injury. The affected cells can recover with treatments that restore the blood flow (reperfusion) which avails oxygen and metabolic substrates to the reversibly injured cells (Ruiz-Meana & Garcia-Dorado 2009). However, if the injury is left untreated and stressors persist for a long time, irreversible injury occurs (O’Neal et al. 2012). The cell structure continues to deteriorate with ongoing cell injury mechanisms. The mitochondrial oxidative process and the glycotic pathway become irreversibly damaged such that reperfusion cannot help the damaged cell. The irreversible injury manifests as necrosis or apoptosis (O’Neal et al. 2012). d. The Pattern of Tissue Necrosis Characteristic of Myocardial Infarction and the Associated Histological Findings at Autopsy A significant myocardium portion is usually affected at necrosis. Coagulative necrosis is a common pattern in myocardial infarction (Masci & Bogaert 2012). The pattern is characterised by gel-like substance formation in dead tissues because of protein denaturation. The albumin in proteins become firm and opaque (Soeiro et al. 2012). The anatomic pathologic diagnosis of myocardial infarction at autopsy relies on both gross and microscopic features (Tsuruyama & Kakimoti 2014). Acute inflammation, oedema and haemorrhage are also visible. The earliest light microscopic depictions of myocardial infarction were thin, wavy mycocytes, visible an hour following infarction. The necrotic mycocytes may retain their striations for a long period, after which the cells lose the striations and nuclei after about 24 to 72 hours following infarction (Tsuruyama & Kakimoti 2014). The inflammation is present with extensive debris of basophiles due to degeneration of the neutrophilis. The necrotic area is surrounded and progressively infiltrated by granulation tissues that will replace the infarct with a fibrous scar (Tsuruyama & Kakimoti 2014). A few days after the infarction, the dead muscle becomes softened and yellowish in colour. Five to ten days after the infarction, it shows a hyperaemic border and a softened yellow shrunken depressed centre. In the end there is fibrosis with dense collagenous connective tissue without inflammation (Soeiro et al. 2012). e. The Major Biomarkers of Myocardial Infarction Measured in Laboratory Investigations of Suspected Myocardial Infarction Laboratory investigation for myocardial infarction is based on measuring the blood levels of intracellular macromolecules (Rosenblat, Zhang & Fear 2012). These macromolecules usually leak out of irreversibly injured myocardial cells through damaged cell membranes. The macromolecules include myoglobin, creatinine kinase (CK), cardiac troponins (TnT and TnI), and lactase dehydrogenase among others (Rosenblat, Zhang & Fear 2012). A diagnosis of myocardial injury, from a biochemical perspective is established if the blood levels of sensitive and specific biomarkers such as cardiac troponins and CK-MB fraction are elevated in the clinical setting of acute ischaemia (Chan & Ng 2010). Cardiac specific proteins especially Troponin-I and Troponin-T are preferred biomarkers for myocardial damage. Troponins are protein in nature and regulate calcium-mediated contraction of both skeletal and cardiac muscle (Tsuruyama & Kakimoto 2014). These markers have almost complete tissue specificity and very high sensitivity. CK-MB fraction is a significant diagnostic indicator. Diagnosis by biological markers depends on time-dependent myocardial cell injury that mainly results from disruption of coronary artery blood flow (Tsuruyama & Kakimoto 2014). Conclusion The report has discussed myocardial infarction from ischaemia to necrosis. At ischaemia, the blood flow to the tissues in the heart muscle is restricted because of events such as arthesclerosis, thromboembolism and trauma that injure the coronary arteries, arthesclerosis being the commonest. Mechanisms that induce injury to the heart muscle include inflammation triggered by the immunity as a cardio-protective measure, nitrogen-oxygen pathways that affect aerobic glycolysis, and the eventual overwhelming of the ATP energy production via the mitochondria. Reperfusion can help to reverse cell injury by using therapies that remove the obstructions and permit blood flow to the tissues. However, persistent ischaemiac conditions results to a point where irreversible cell damage occurs, leading to cell death by necrosis or apoptosis. Histological analysis of myocardial infarction reveals coagulative necrotic patterns that change depending with duration from infarction. Major biomarkers for myocardial infarction in laboratory investigations include cardiac troponins and creatinine kinase. List of References: Chan, D. & Ng, L.L. 2010, "Biomarkers in acute myocardial infarction", BMC Medicine, vol. 8, pp. 34. 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