Atherosclerosis Flashcards
atherosclerosis is a _____ disease affecting ….
systemic, large and medium-sized arteries
what is atherosclerosis characterized by? complications of atherosclerosis account for _______ of all deaths in the western worlds
by the formation of atheromas (fibrofatty plaques) which narrow (stenose) the artery lumens, resulting in blood-flow reduction (ischemia) and subsequent damage or necrosis to the “downstream” organs.
Complications of atherosclerosis account for more than half of all deaths in the Western world.
pathogenesis of atherosclerosis
The earliest pathological lesion is called a fatty-streak. Some of these slowly progress and develop into the mature atherosclerotic lesion, the fibro-fatty plaque.
what does the response to injury hypothesis explain
explains plaque development as a chronic inflammatory response resulting from injury to the endothelial lining of the artery
Many of the atherosclerotic risk factors (subsequently discussed) act by contributing to….
- this results in…
- how do you get to the end result
some form of epithelial damage
-endothelial dysfunction, allowing for platelets and monocytes (macrophages) to adhere to the lining. These elements release various growth factors and cytokines, which cause recruitment and migration of smooth muscle cells and fibroblasts into the endothelium. Collagen is produced. Macrophages also engulf lipid and cholesterol derived from the blood. The end result is a raised plaque, with both fibrous and fatty elements, which narrows the vessel lumen.
3 major risk factors for astherosclerosis
-what is an important feature of these?
smoking, hypertension, and elevated blood cholesterol. An important feature of all three is that they are potentially modifiable
what is also a major risk factor for atherosclerosis that isnt considered the big 3
diabetes mellitus
non-modifiable risk factors of atherosclerosis
age, sex (premenopausal women at lower risk but catch up to men after menopause), family history, ethnicity, obesity, lower socioeconomic class, type “A”
personality/stress, elevated blood homocysteine level
protective factors
moderate alcohol consumption
Major sites of atherosclerotic ischemic injury and therefore clinical disease are:
Heart - causing angina pectoris, myocardial infarction, chronic heart failure, sudden cardiac death
Brain - ischemic stroke
Extremities - claudication, gangrene
Kidneys - chronic kidney failure
epidemiology of ischemic heart disease
mortality rate of IHD (ischemic heart disease) has been declining since the 1960s but it remains a leading cause of death. However, the rate has been steadily increasing in developing countries (due partly to increasing life expectancy and also to acquiring bad “Western” lifestyle habits) and therefore the overall global burden of IHD is on the rise.
the heart receives its blood supply from
coronary arteries
3 major branches of the coronary arteries and what they supply
the left anterior descending (LAD) branch and the left circumflex branch supply the anterior and lateral portions of the left ventricle respectively, and the right coronary artery (RCA) supplies the right ventricle and the posterior wall of the left ventricle.
Coronary atherosclerosis begins _________ and is ______ progressive
early life (20s), slowly
when does coronary atherosclerosis manifest clinically with symptoms? what is this due to?
until later in life when there is reduction in blood flow of a magnitude which can potentially cause ischemic damage (necrosis) of heart muscle
the degree of flow reduction that causes ischemia of the heart muscles until there is about __% reduction in the…
70% area of the coronary artery lumen
What is angina and what is it the result from
chest pain which is the result of myocardial ischemia, and this blood flow reduction is usually due to coronary atherosclerosis.
what is stenosis
abnormal narrowing of a body channel
in angina pectoris, what is there usually in terms of the arteries?
at least one coronary artery with a fixed severe stenosis although vasospasm (muscular constriction of the vessel wall) can further contribute to the narrowing
the pain of angina is usually describes as
“crushing, tightness or heaviness”
why cant angina result in necrosis of heart muscle
myocardial ischemia is of insufficient duration and magnitude to result in actual death (necrosis) of the
downstream heart muscle
how is angina precipitated? how do episodes resolve?
by events that increase myocardial blood flow
demand such as exercise or stress. Episodes usually resolve with rest or medications (nitroglycerine).
If myocardium is ischemic for about __________, it begins to die, and the result is a_________.
30-40 mins, myocardial infarction
What are most MIs precipitated by?
What did awareness of this lead to
formation of a thrombus on the luminal surface of a coronary artery plaque, causing complete or near-complete occlusion of the vessel (the thrombus is the “straw that breaks the camel’s back”).
Awareness of this led to the development of thrombolytic drugs (“clotbusters”) which are highly effective in re-establishing coronary blood flow and either preventing or reducing infarction. These drugs must be administered promptly, again emphasizing the importance of early diagnosis & treatment.
other treatments for MI
Other treatments include percutaneous transluminal coronary angioplasty (dilatation of a stenosis by inflation of a balloon catheter) or coronary artery bypass surgery. (both of these treatments can also be given for unstable angina to prevent infarction)
clinical symptoms of MI
- prolonged “angina-like” chest pain, often radiating to jaw or left arm, associated nausea and sweating (diaphoresis).
other ways to diagnose MI
- changes on the electrocardiogram (ECG) which can indicate heart muscle injury
- measuring elevated levels of cardiac enzymes such as troponins and cardiac muscle creatine kinase (CK-MB). These substances are specific to heart muscle and they leak into the blood when heart muscle cells are injured and dying
MIs most often involve the _____ _________
left ventricle
what does transmural mean? what does subendocardial mean?
If an infarct involves the full thickness of the wall
If it involves only the inner half of the wall
how do infarcts heal
heal by a process of scarring; muscle does not regenerate. Therefore, infarcted muscle is “lost” to the heart which has to rely on its remaining muscle to keep it functioning
- Healing starts with removal of the dead muscle. This requires the digestive proteolytic and phagocytic action of neutrophils and macrophages.
- This is followed by ingrowth of fibroblasts which produce and lay down collagen which forms the bulk
of the scar
- Scar is usually well-developed after 2 months
early complications of MI
Dysrythmias - disturbances in the electrical rhythm of the heart. Infarcted muscle can interfere with the normal conduction of electrical impulses through the heart. These can be serious and potentially fatal and
often require either drugs or electrical pacemakers.
Congestive heart failure/cardiogenic shock - if too much muscle is infarcted and the remaining living muscle cannot meet the demands required of the heart, the result is “back-up” congestion of blood in the lungs (congestive heart failure) and inadequate forward flow of blood to the body (cardiogenic shock)
Ventricular rupture - sometimes the infarcted zone cannot hold together and the heart wall ruptures, causing acute hemorrhage into the sac around the heart which in turn compresses the heart (cardiac
tamponade) and is almost always fatal
Pericarditis (inflammation of the heart surface) can be either an early or late complication
late complications of MI
- An end-stage scar from a large transmural infarct can weaken and bulge, forming an aneurysm of the LV
wall - Congestive heart failure can be a chronic condition
Hypertension is generally accepted as __ / __ or greater
140 / 90
about ___% of the population is hypertensive
25
only about ___% of hypertensive Canadians know they are hypertensive
only ___% of hypertensive Canadians have adequate blood pressure control
50 , 16
BP = _______ x _________
BP = cardiac output x peripheral vascular resistance
cardiac output depends on what 2 things
heart rate and stroke volume
what is peripheral resistance controlled by?
d by the balance of constricting and dilating humoral and neural factors on blood vessels (e.g. epinephrine is a vasoconstrictor)
how does the kidney play an important role in BP regulation
o Sensing a drop in BP, the kidney will release the hormone renin which in turn activates the vasoconstrictor angiotensin
o The kidney also controls the body’s sodium balance which in turn influences the blood volume
primary hypertension is also called
essential or idiopathic
___% of cases are primary hypertension
90
almost any renal disease can result in ….? why?
Because the kidney is so important for BP regulation, almost any renal disease can result in HTN
how can endocrine disease result in hypertension
can result in elevated hormone levels which can increase BP via their vascular constricting influence. (e.g. an epinephrine-secreting tumour of the adrenal gland). Hyperthyroidism is another example of an endocrine cause of HTN
what is white coat HTN
A patient
may get nervous and stressed when having their BP measured in a medical setting, but when checked in
a relaxed setting it is normal.
why has HTN been labelled the silent killer
because it doesn’t cause symptoms until damage occurs in vital organs
What damage does HTN result in
the consequence of the effects that HTN has on arteries, both large and small. In small arteries (arterioles), HTN causes hyaline arteriosclerosis-their walls become thickened and their lumens narrowed. In larger arteries, the stresses of HTN cause accelerated atherosclerosis (recall from prior notes that HTN is a major risk factor for atherosclerosis).
What 3 major organs does HTN cause vascular damage
Kidney -HTN results in nephrosclerosis, a major cause of renal failure, because it damages the main functioning unit of the kidney, the glomerulus (a specialized small arterial/capillary structure which filters urine).
Heart - HTN affects the heart in two ways. Firstly, it contributes to coronary atherosclerosis and all of its ischemic heart complications. Secondly, increased blood pressure increases the workload of the heart which adapts by undergoing hypertrophy (ie. Increases its muscle mass). Eventually, the heart may be unable to
compensate and the end result may be congestive heart failure.
Brain - HTN-induced arteriosclerosis also affects small arteries supplying the base of the brain. These damaged vessels can rupture, resulting in hemorrhagic strokes. HTN also accelerates atherosclerosis of large
arteries supplying the brain and the result can be an ischemic stroke if these vessels are sufficiently
