Cardiovascular Disease Flashcards
ATHEROSCLEROSIS - basics
Atherosclerosis is a systemic disease affecting large and medium-sized arteries.
Fibrofatty plaque:
- fibrous cap
- necrotic centre
- media
It is wax and hardening
It is characterized 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.
Atherosclerosis - Pathogenesis
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.
Atherosclerosis - response to injury hypothesis
The “response to injury hypothesis” explains plaque development as a chronic inflammatory response resulting from injury to the endothelial lining of the artery.
Many of the atherosclerotic risk factors act by contributing to some form of endothelial damage.
- This “damage” results in 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.
Atherosclerosis - Risk Factors
The “big three” major risk factors are smoking, hypertension, and elevated blood cholesterol (hyperlipidemia).
- An important feature of all three is that they are potentially modifiable (can be improved through prevention or treatment).
- Relative risk is multiplied, not added, when 2 or 3 of these factors are present.
20 cigarettes per day increases risk of CV death by 2 times
Cholesterol is transported by lipoproteins
- LDL is bad, HDL is good
- blood levels are determined by genetics and diet
- drug treatment sometimes needed
Diabetes mellitus is also a major risk factor, modifiable with treatment.
Non-modifiable risk factors include - older age, male sex (premenopausal women at lower risk but catch up to men after menopause), family history, ethnicity
Other factors, potentially modifiable - obesity, lower socioeconomic class, type “A” personality/stress, elevated blood homocysteine level, physical inactivity, post menopausal estrogen deficiency
Protective factors (reduced risk) - moderate alcohol consumption.
MANIFESTATIONS OF ATHEROSCLEROSIS
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
Note that many patients may have coexisting atherosclerotic disease in more than one organ system.
ATHEROSCLEROTIC CORONARY ARTERY DISEASE
The heart requires a large supply of oxygen and nutrients.
- It receives its blood supply via the coronary arteries which originate from the aorta just beyond the aortic valve.
- There are three major branches; 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.
- These are medium-sized arteries, and therefore susceptible to atherosclerosis.
Coronary atherosclerosis begins early in life (20’s) and is slowly progressive.
- It does not become manifest clinically with symptoms until later in life when there is reduction in blood flow of a magnitude which can potentially cause ischemic damage (necrosis) of heart muscle.
- This degree of flow reduction does not occur until there is about a 70% reduction in the area of the coronary artery lumen (there is a large “safety margin” of flow).
Epidemiology - ATHEROSCLEROTIC CORONARY ARTERY DISEASE
IHD = ischemic heart disease
In Western society, the mortality rate of IHD has been declining since the 1960’s but it remains the 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.
Angina Pectoris - ATHEROSCLEROTIC CORONARY ARTERY DISEASE
Angina is chest pain which is the result of myocardial ischemia, and this blood flow reduction is usually due to coronary atherosclerosis.
There is usually 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 is usually described as “crushing, tightness or heaviness”.
By definition, the resultant myocardial ischemia is of insufficient duration and magnitude to result in actual death (necrosis) of the downstream heart muscle.
Angina is often precipitated by events that increase myocardial blood flow demand such as exercise or stress.
Episodes usually resolve with rest or medications (nitroglycerine).
Exertional ischemic pain resolves before necrosis occurs
unstable angina can herald impending infarction
MYOCARDIAL INFARCTION - pathogenesis
If myocardium is ischemic for about 30-40 minutes, it begins to die, and the result is a myocardial
infarct (MI).
- It is therefore important to seek prompt medical attention when an anginal episode does not
resolve within this time period.
Most MI’s are precipitated by 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”).
- in 90% of cases
MYOCARDIAL INFARCTION - treatment
Medical/preventative:
- There has been the development of thrombolytic drugs (“clot- busters”), 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. So that muscle does not die
- lipid lowering agents
- anti-hypertensives
- risk factor reduction
Surgical/interventional:
- 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)
MYOCARDIAL INFARCTION - diagnosis
Diagnosis is made by;
o clinical symptoms - prolonged “angina-like” chest pain, often radiating to jaw or left arm, associated nausea and sweating
o changes on the electrocardiogram (ECG) which can indicate heart muscle injury
o Measuring elevated levels of cardiac enzymes such as troponins and cardiac muscle creatine kinase. These substances are specific to heart muscle and they leak into the blood when heart muscle cells are injured and dying
MYOCARDIAL INFARCTION -
Morphological and Histological Features
MIs most often involve the left ventricle (it works much harder than the right ventricle and therefore demands much more blood flow)
The affected area usually corresponds to the territory supplied by the narrowed “culprit” coronary artery.
- Therefore, blockages of the LAD result in anterior wall infarcts (50%), left circumflex artery blockages (20%)
infarct the lateral LV wall and RCA blockages (30%) infarct the posterior LV wall and posterior septum.
Infarct size is variable; prognosis is worse for larger lesions
If an infarct involves the full thickness of the wall, it is termed transmural
If it involves only the inner half of the wall (the furthest “downstream” muscle), it is termed subendocardial
Progression occurs from inside of the heart to the outside
- inside portion of the heart is least perfused and is more susceptible to ischemia because the obstructed coronary artery is on the outside of the heart
- zone of necrosis starts inner then goes to outer layer
Infarcts 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 Myocardial Infarction
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 Myocardial Infarction
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
