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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.

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