Cardiovascular Disease - Atherosclerosis Flashcards
Atherosclerosis
- a systematic disease affecting large and medium-sized arteries
- characterized by the formation of atheromas (fatty plaques) which narrow (stenosis) the artery lumens -> high blood-flow reduction (ischemia) and damage or necrosis to “downstream” organs - end-organ damage (symptomatic disease)
- complications account for atherosclerosis account for more than half of deaths in the West of the world
- spindle-shaped empty spaces - cholesterol clefts, calcium black and blue
- 70-75% symptomatic luminal stenosis correlating with patients
- surface can become irregular
- Ulceration plugs which can form thrombus -> collusion
- Plaques develop as a result of a chronic inflammatory reaction to various forms of injury/insult to the endothelium
- Atheroma (fibrofatty Plaque) - Fibrous cap - Smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularization - Necrotic center - Cell debris, cholesterol, crystals, foam cells, calcium -Media - Formation of clot
Major / Modifiable Risk Factors
Cigarette Smoking:
- single most important modifiable risk
- 400,000 die a year in the US
- 20/day = death % doubles
Hyperlipidemia:
- Cholesterol transported by lipoproteins
- LDL (low-density lipoproteins) = “bad” cholesterol
- HDL (High-density lipoproteins) = “good” cholesterol
- blood levels determined by genetic influence and diet
- Pharmacological treatment is sometimes necessary
Hypertension:
- silent killer / asymptomatic
- underdiagnosed
- Undertreated
Diabetes Mellitus:
- a strong risk factor
- mechanism of distribution is multifactorial
- Risk of coronary heart disease is doubled
- increased risk of gangrene in extremities with peripheral vascular disease
Major / Non-modifiable Risk Factors
Factors:
- old age
- family history
- male gender
Other:
- obesity
- lower socio-economic class
- physical inactivity
- stress / A type personality
- Homocysteine - substance presented in blood, toxic effects, clotting factors, Vitamin B
- Post-menopausal estrogen deficiency - estrogen paradox (hormones have protection effects only on own gender)
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, gray matter lost)
- Extremities - Claudation (ischemic type pain, stenosis of vessels to the left femoral, popliteal, lower leg arteries) - Gangrene (complete blockage of the vessel by significant stenosis or superimposed clot, necrotic and inflamed tissue, requires amputation, high risk to get if have atherosclerosis + diabetes)
- Kidneys - chronic kidney failure
Atherosclerosis Coronary Artery Disease
- heart requires a large number of nutrients and oxygen.
- the heart is a very vascular organ
- it receives blood from the coronary arteries which originate from the aorta just beyond the aortic valve
- three major branches: left anterior descending (LAD) branch, left circumflex branch supply the lateral and anterior portions of the left ventricle, right coronary artery (RCA) supplies the right ventricle and the posterior wall of the left ventricle
- 3 branches are medium arteries - susceptible to atherosclerosis
- begins early 20s, slowly progressing, symptoms do not manifest until later
- degree of flow does not occur until 70% reduction
Angina Pectoris
- Exertional ischemic pain resolves before necrosis occurs
- Unstable angina can herald impending infarction
- Ischemic type of cardiac pain
- Usually occurs during times when high oxygen supplies are needed - exercise or stress
- Transient event - solved with rest and medications (nitroglycerine)
- When pain does not go away = higher risk of cardiac infarction
Coronary artery reaches critical stenosis - 75-80%
Myocardial Infarction (MI)
- Ischemic necrosis of heart muscle
- Muscle begins to die after about 30 minutes of ischemia
- Diagnosis made by symptoms, EGG changes and cardiac enzyme rise (cells die and go into the bloodstream where they can be measured) - troponins and creatine kinase elevation in blood
- prolonged angina, radiating to jaw or left arm, associated with sweating and nausea
- Often precipitated by coronary thrombosis on the luminal surface of a coronary artery plaque
- complete or near complete occlusion of the vessel
- thrombolytic drugs (clot busters) that prevent/reduce infarction
- treatment includes percutaneous transluminal coronary angioplasty
Acute Myocardial Infarct
- Coronary thrombosis in 90%
- Thrombolytics - “clots-busters’ used to re-establish blood flow
- Early treatment very important - must be given before the muscle dies
Usually smaller in size
Coronary Distribution - MI site
- The site of myocardial infarction is determined by which coronary arteries are involved with thrombosis - Left main coronary artery give branches into left anterior descending
- If blocked, myocardial infraction with be in the distribution of the diagram
- More common involved in hard working - high % of infarct - Right main coronary artery - Posterior wall blockage
- Myocardial infarct can invoke full blown sickness
- transmural myocardial infarct (full thickness of wall) or partial sickness - Usually associated with complete luminal occlusion
Morphological and Histological Features
- Mls involves the left ventricle (pumps more blood)
- affected area depends on territory supplied by the narrowed “culprit”
- LAD blockages = anterior wall infarcts
- left circumflex artery blockage = infarct in the lateral LV wall
- RCA blockage = posterior LV wall
- full wall thickness infarct - transmural
- furthest downstream muscle and involves half the inner wall - subendocardial
- infarcts healing by scarring - muscles do not regenerate
- healing starts with the removal of dead muscle - digestive proteolytic and phagocytic action of neutrophils and macrophages
- fibroblasts which produce and lay down collagen - forms scars
- scar well developed after 2 months
Progression of Myocardial Infarct
- infarct will be formed beyond the blockage point - distally to the blocked portion of the vessel - Happens from inside the heart –> outside because coronary arteries epicardial is on the surface and it supplies from the outside
- Inside portion of the heart will be least perfused and more susceptible to ischemia
- If less than half of the myocardium is involved, it’s cardio infarct
- Full sickness, more than half-transmural
- Normal infarct - microscopically - Each cell has a nucleus, some connective tissue, fine cross-triation, normal cardiomyocytes
- Acute infarct - microscopically - Necrosis of cardiac muscle, becomes intense, losing nuclei - Cardiomyocytes and neutrophils will migrate to an area to digest all necrotic debris - Migration of fibroblasts, deposit collagenous tissue, inflammatory cells, macrophages, lymphocytes and development of blood vessels (new< quite to supply scar formation)
Myocardium tissue does not regenerate - replaced by scar
MI Complications
Arrhythmias
- the most common cause of death
- Can happen at anytime
- Can die before microscopic or gross changes in blood vessels
Sudden Death
- After the onset of cardiac-type pain
- See thrombosis or significant stenosis
- Can happen early in myocardium infarction and later due to scar tissue
Cardiogenic Shock
- Heart has myocardial infarct, heart cannot pump blood
- Conditions that comes from inability of heart pumping blood to end organs and end organs getting damaged
Congestive heart failure
- Heart has myocardial infarct, heart cannot pump blood
- Comes from backlog of blood in the venous circulation because the heart is not able to pump blood
- Congestion in the lungs, liver, and spleen, that can result in generalized edema as well
- chronic condition
Pericarditis
- Can develop in acute or later stages of myocardial infarction
- Exudate on surface
- swelling/irradiation of pericardium
Rupture
- Usually, acute complication
- Several days of onset of infarct
- Takes time for the tissue to become necrotic - high risk of rupture
- Defects at the apex of the heart, blood accumulates in pericardial SAC, compressing the heart (cardiac tamponade)
- Very serious, very fatal - the heart is not able to pump blood when a significant amount of blood accumulates
- heart wall ruptures and causes hemorrhage
Aneurysm
- Mural - area replaced by scar and outpouching
- Do not usually rupture but are associated with congested heart failure
Therapeutic Strategies
Medical/preventative
- Risk factor reduction
- Anti-hypertensives
- Lipid Lowering Agents
- Thrombolytics - before cardiac muscle dies
Surgical/Interventional
- Coronary artery bypass
- Angioplasty
Angioplasty and Stenting
- Other names: percutaneous transluminal coronary angioplasty -Through the skin and transluminal while operating within the lumen of the vessel
- Guided wire is used + deflated balloon
- Stent opens, crushes atherosclerosis plaque and keeps the vessel open
- Balloon is then deflated and removed
- Flexible wire
- Use catheter
Coronary Artery Bypass Grafting
- Another surgical intervention for coronary arteries
- For larger segments of stenosis - when angioplasty can not be used
- Significant stenosis
- Usually, vessels behind the sternum
- Can put in several bypasses
