This thesis examines the pathogenesis of ischemic heart disease. The aims are to study epidemiological issues, causes and risk factors, pathophysiological mechanisms of ischemia, ischemic syndromes and complications, and the pain mechanism. Ischemic heart disease, also called coronary artery disease, results from an imbalance between myocardial blood supply and oxygen demand caused by atherosclerosis. The thesis will analyze the disease pathogenesis to further understand this leading cause of death worldwide.
This thesis examines the pathogenesis of ischemic heart disease. The aims are to study epidemiological issues, causes and risk factors, pathophysiological mechanisms of ischemia, ischemic syndromes and complications, and the pain mechanism. Ischemic heart disease, also called coronary artery disease, results from an imbalance between myocardial blood supply and oxygen demand caused by atherosclerosis. The thesis will analyze the disease pathogenesis to further understand this leading cause of death worldwide.
This thesis examines the pathogenesis of ischemic heart disease. The aims are to study epidemiological issues, causes and risk factors, pathophysiological mechanisms of ischemia, ischemic syndromes and complications, and the pain mechanism. Ischemic heart disease, also called coronary artery disease, results from an imbalance between myocardial blood supply and oxygen demand caused by atherosclerosis. The thesis will analyze the disease pathogenesis to further understand this leading cause of death worldwide.
Public Institution “Nicolae Testemițanu” State University of Medicine and
Pharmacy of the Republic of Moldova
Department
DIPLOMA THESIS
PATHOGENESIS OF ISCHEMIC HEART
DISEASE NAME AND SURNAME OF STUDENT YEAR, GROUP
NAME AND SURNAME OF SCIENTIFIC ADVISOR
POSITION AND SCIENTIFIC DEGREE PURPOSE OF THE THESIS
The aim of this study is to critically review the
pathogenesis of ischemic heart disease to provide an improved understanding of its basis and complexity. OBJECTIVES OF THE THESIS 1. To study the epidemiological issues of ischemic heart disease. 2. To determine causes and risk factors for development of coronary artery disease. 3. To identify the major pathophysiological mechanisms of the ischemic process. 4. To explain the pathophysiology of various ischemic syndromes and complications of CAD. 5. To explain the pain mechanism in IHD. THEORETICAL IMPORTANCE AND VALUE OF THE WORK • Because coronary heart disease is the most serious and catastrophic cause of illness and death worldwide, refinements and theoretical understandings of a subject are constantly being attempted and investigated. • This work summarizes our current understanding of the pathogenesis of this acute problem to define and ultimately reduce its incidence. DEFINITION The world ischemia is derived from two Greek worlds iscko, meaning to hold back, and haima, meaning blood. In Latin it is known as morbus ischaemicus cordis. Thus, ischemic heart disease also called as coronary artery disease (CAD) or coronary heart disease (CHD) is the medical term given to myocardial ischemia, which is caused by an imbalance between myocardial blood supply and oxygen demand. EPIDEMIOLOGICAL ISSUES It is the major cause of morbidity and mortality. It is estimated that every year approximately 50% of males over the age of 45 years and 30% of females over the age of will develop coronary artery disease. According to the World Health Organization (WHO), about 110 million people have CAD every year, which resulted in 8.9 million deaths worldwide. In Republic of Moldova, CHD is the most common form of cardiovascular disease, accounting for 60% of all deaths. according to Framingham study- male: female ratio=2:1. It may affect individuals at any age but becomes more common in older ages, ~ a tripling with each decade. Regarding racial differences, CAD is higher in blacks than in whites. ETIOLOGY OF IHD Atherosclerosis is the major cause of CAD.
Although there are numerous unusual causes of cardiac
ischemia, like: coronary embolism, coronary artery dissection, aortic dissection with coronary occlusion, congenital coronary artery anomalies, coronary vasospasm, thyrotoxicosis, vasculitis and restenotic disease. RISK FACTORS OF IHD PATHOPHYSIOLOGY OF THE ISCHEMIC PROCESS Several risk factors impair normal endothelial function and increase its permeability by reducing bioavailability of nitric oxide. So, the process begins as disruption of endothelial function due to the accumulation of low density lipoprotein (LDL) droplets in the intima of the coronary vessels where it undergoes oxidation and, in diabetics, glycation. Oxidized/modified LDL particles are potent chemotactic molecules that induce expression of vascular cell adhesion molecule and intercellular adhesion molecule at the endothelial surface, and promote inflammatory cells. Once in the subendothelial space, they undergo differentiation, becoming macrophages. Macrophages digest oxidized low-density lipoprotein (LDL), transforming into foam cells. These cells replicate giving rise to fatty streaks, one of the earliest pathological lesions. Other types of cells such as T-lymphocytes, neutrophils and mast cells, also accumulate in the subendothelial space. The activated macrophages release chemoattractants and cytokines (eg, monocyte chemoattractant protein 1, tumor necrosis factor α, and interleukins) that perpetuate the process by recruiting additional macrophages and vascular smooth muscle cells(VSMC) at the site of the plaque. VSMC proliferate and manufacture extracellular matrix components (collagen and proteoglycan) which occupied a large volume of the plague. The fatty streak is now transformed into the fibrous plaque. PATHOPHYSIOLOGY OF THE ISCHEMIC PROCESS The final lesion, the advanced complicated lesion, consists of a fibrous cap overlying a lipid rich core which also contains necrotic material, this core is highly thrombogenic. The edge of the fibrous cap (the shoulder region) plays a critical role in the development of acute coronary syndromeas. The shoulder region is the site where most plaques lose their integrity or rupture. Plaque rupture exposes the underlying thrombogenic core of lipid and necrotic material to circulating blood and its thrombogenic particulates. This exposure results in platelet adherence, aggregation, and progressive luminal narrowing, which can rapidly progress and often in the absence of coronary artery collateral development are associated with acute coronary syndromes. PATHOPHYSIOLOGY OF THE ISCHEMIC PROCESS PATHOPHYSIOLOGY OF THE ISCHEMIC PROCESS • The major pathophysiological difference between acute coronary syndromes (ACS) and stable angina pectoris is rupture of the atherosclerotic plaque with subsequent thrombosis formation that causes the acute events.
• Plaque rupture occurs independently of lesion size and degree of
stenosis and some plaques seem to be more vulnerable than others are. PATHOPHYSIOLOGY OF THE ISCHEMIC PROCESS SPECTRUM OF MYOCARDIAL DYSFUNCTIO FOLLOWING ISCHEMIA PAIN MECHANISM IN IHD • Once myocardial perfusion is reduced, aerobic glycolysis and lipolysis cease almost immediately, while anaerobic glycolysis is transiently stimulated.Thus lactate concentration increases and pH is lowered. This rapidly results in a decrease in the adenosine triphosphate (ATP) to adenosine diphosphate (ADP) ratio and generation of adenosine, which in turn leads to further dilatation of the coronary pre-arterioles. when the epicardial artery is significantly stenosed, no further blood supply is available and the adenosine levels rise significantly. So, contractility is also abolished and K+ accumulates extracellular, as Na-K ATPase activity is reduced. • The accumulations of immune and inflammatory cells results in immune response and releasing of such substances as bradykinin, eicosanoids and substance P. This collage of chemicals (where the most important are adenosine and bradykinin), excite the chemo sensitive and mechanoreceptive receptors of the sympathetic and vagal afferent pathways. • Sympathetic afferent fibers from the heart (via unmyelinated C fibres and myelinated Aδ fibres) enter the upper thoracic spinal cord and synapse on cells of origin of ascending pathways[21,53]. The resulting neural outflow appears to be responsible for the resulting sensation of visceral pain or discomfort, which manifests clinically as angina pectoris. PAIN MECHANISM IN IHD MATERIALS AND METHODS OF THE RESEARCH This study was conducted through searching in related books and articles. The related articles were retrieved from authorized database such as Hinary, Elsevier and PubMed using keywords such as (ischemic heart disease, coronary artery disease, coronary heart disease, myocardial ischemia, pathogenesis, ischemic syndromes, pain mechanism and atherosclerosis) from 1995 to 2012. So, this study focuses on the general information and epidemiological aspects of ischemic heart disease; its etiology; the main risk factors; pathophysiological mechanisms of the ischemic process; spectrum of myocardial dysfunction following ischemia; acute coronary syndromes and pain mechanism in ischemic heart disease. Only books and articles written or translated into English were included. PERSONAL OBSERVATIONS AND DISCUSSION Coronary artery disease (CAD) is a leading cause of death of women and men worldwide. An estimated 110 million people died from this cause in 2015, representing 30 % of all deaths in the world and its prevalence is expected to increase in the coming years. PERSONAL OBSERVATIONS AND DISCUSSION According to Mozaffarian et al.(2008) IHD has a complex etiopathogenesis and a multifactorial origin related to environmental factors, such as diet, smoking, and physical activity, and genetic factors that modulate risk of the disease both individually and through interaction PERSONAL OBSERVATIONS AND DISCUSSION Atherosclerosis is the main etiopathogenic cause of coronary artery disease and with endothelial dysfunction leads to an imbalance between myocardial oxygen supply and demand. The process of atherosclerotic plaque progression is considered to be dynamic and complicated. So, IHD is a complex process that proceeds through a series of pathological events involving the cardiovascular system, the inflammatory and immune systems, lipid and cholesterol handling mechanisms and blood clotting mechanisms. PERSONAL OBSERVATIONS AND DISCUSSION Accordingly to multiple studies, myocardial ischemia can have a number of consequences and various clinical manifestations, including stable angina, acute coronary syndrome, and sudden cardiac death. As is shown .
The type of ACS depends on the
degree of coronary obstruction and associated ischemia. GENERAL CONCLUSIONS 1. Ischemic heart disease (IHD) is the leading cause of disability/ morbidity and death worldwide.
2. The recognized risk factors for CVD are multifactorial and interact over time to produce the disease and include modifiable and not preventable one.
3. The most common cause of CAD is atherosclerosis, which
progressively narrow the coronary artery lumen and impair myocardial blood flow. The reduction in coronary artery flow may be symptomatic or asymptomatic. GENERAL CONCLUSIONS 4.Atherosclerosis is a chronic process involving the endothelial dysfunction and lipid infiltration, cell adhesion, immune and inflammatory response.
5.The disease typically comes in one of three forms: angina pectoris, an
acute coronary syndrome including myocardial infarction and unstable angina, or sudden cardiac death and it depend on obstruction severity and the rapidity of development.
6.Cardiac pain in CAD is generate like response to hypoxia increases and
include metabolic changes, peripheral and central nervous system, including activation of CNS areas known to be responsible in pain syndromes.