Lecture 14: Ischemic hearth disease Flashcards
what is the myocardial infarction?
the heart is cell death
due to insufficient arterial blood supply from the coronary arteries for the tissue’s needs.
what are the causes of myocardial infarction?
–95% Coronary artery atheroma
–Rarely: Insufficient blood supply due to other causes, Shock, Massive LVH or cardiac hypertrophy
what are the non-atherosclerotic causes of AMI?
1) Coronary artery dissection
2) Coronary artery vasospasm (e.g., Prinzmetal angina, cocaine use)
3) Takotsubo cardiomyopathy
4) Myocarditis
5) Thrombophilia (e.g., polycythemia vera)
6) Coronary artery embolism (e.g., due to prosthetic heart valve, atrial fibrillation)
7) Vasculitis (e.g., polyarteritis nodosa, Kawasaki syndrome)
8) Myocardial oxygen supply-demand mismatch
- -Hypotension
- -Severe anemia
- -Hypertrophic cardiomyopathy
- -Severe aortic stenosis
what are the 3 main coronary arteries?
1)Left coronary artery- 1.5cms and gives rise to the interventricular LAD and the (L) circumflex.
• The LAD supplies the apex, anterior 2/3 of septum and the anterior wall of the LV.
2)Right coronary artery classically the posterior wall “inferior” in ECG.
• The right coronary artery usually supplies the posterior of the septum
why thrombus complicating coronary atheroma may be more catastrophic in a seemingly previously well patient?
- In normal hearts or in cases of moderate (20-50% stenosing) atheroma the arteries are effectively end arteries.
- In abnormal hearts, a collateral circulation may develop
what is the ischemic heart disease?
There are a number of clinical syndromes reflecting varying pathology 1)Angina pectoris – Stable – Unstable 2)Myocardial infarction 3)Chronic ischaemic heart disease
what is stable angina?
A type of angina that occurs upon exertion, mental stress, and/or exposure to cold and usually subsides within 20 minutes of rest or after administration of nitroglycerin. Occurs due to a mismatch in myocardial oxygen supply and oxygen demand from underlying coronary artery disease.
–Reflects “Significant” atheroma:
one vessel > 75% stenosis or 2 > 50% as rule of thumb.
–Assessment via angiography. Often if autopsy done see microscopic myocardial fibrosis. Angina may be worsened by anaemia or
increased cardiac mass i.e. hypertrophy:
therefore may reflect important non-cardiac disease
what is unstable angina?
–Symptoms are not reproducible/predictable
–Usually occurs at rest or with minimal exertion and is usually not relieved by rest or nitroglycerin
–Every new-onset angina
–Severe, persistent, and/or worsening angina (crescendo angina)
–Increasing intensity, frequency, or duration in a patient with a known stable angina
–Precipitated with progressively less effort.
– Often occurs at rest, and tends to be of more prolonged duration.
–Induced by disruption of an atherosclerotic plaque (plaque rupture) and secondary thrombus.
unstable angina is induced by…
disruption of an atherosclerotic plaque (plaque rupture) and secondary thrombus.
what is the sudden cardiac death?
A sudden, unexpected death that occurs within 1 hour of symptom onset as a result of cardiac arrest (e.g., from ventricular fibrillation, pulseless ventricular tachycardia, asystole, and/or pulseless electrical activity). The most common underlying cause of SCD in elderly individuals is acute coronary syndrome; causes of SCD in young patients include cardiomyopathies, prolonged QT syndrome, Brugada syndrome, and myocarditis. Implantable cardioverter-defibrillators (ICDs) are used as primary prevention in patients at high risk of SCD.
SCD can arise as a result of…
(1) Sudden large coronary thrombosis on a ruptured atheromatous plaque
(2) Secondary to an arrhythmia in chronic ischaemic heart disease. 50% dead before arrival in hospital
Mechanism – ventricular Fibrillation.
(3) Coronary arterial spasm e.g. cocaine use - rare
what is MI?
• Myocardial necrosis due to reduced blood supply:
Usually reflects unrelieved coronary artery occlusion evolving to tissue death – dynamic process and can be reduced by coronary reperfusion following “stenting”
• Certain plaques more likely to thrombose – lipid-rich with fibrous cap cracks
a lipid poor with fibrous cap cracks are more prone to thrombose. TF
F
lipid-rich with fibrous cap cracks
what is the clinical presentation of MI?
–Crushing central chest pain, unrelieved by rest; accompanied by weakness, sweating, nausea & vomiting
– Radiates commonly to left shoulder and jaw
–May be described as indigestion
–Can be painless - old/diabetes
–Pain may be atypical abdominal.
–May be “silent” present as heart failure (esp in elderly) arrhythmia – confusion – weakness.
–Need a high index of suspicion.
what are the angina pain characteristics?
- -Typically retrosternal chest pain or pressure
- -Pain can also radiate to left arm, neck, jaw, epigastric region, or back.
- -Pain does not depend on body position or respiration
- -No chest wall tenderness
- -Angina may be absent, particularly in younger patients
- -Often gradual progression
- -Can also present as gastrointestinal discomfort
what are other signs that can be seen in angina?
- -Dyspnea
- -Dizziness, palpitations
- -Restlessness, anxiety
- -Autonomic symptoms (e.g., diaphoresis, nausea, vomiting, syncope)
what is the pathophysiology of MI
• Coronary atheroma and plaque rupture and subsequent thrombosis initiate ischemia – possibly reversible for 6 – 12 hours.
• Necrosis of myocardium begins 30 mins after occlusion but there is a progression from the subendocardial myocardium through the full thickness of the myocardium to the pericardial zone. (Transmural infarct)
–Most untreated episodes of ischemia cause Transmural infarction.
• NB Subendocardial (AKA Non-ST-elevation MI– NSTEMI) infarction more likely in the incomplete artery occlusion
when does necrosis begin after artery occlusion?
after 30 min
how necrosis in MI progresses?
from the subendocardial myocardium through the full thickness of the myocardium to the pericardial zone. (Transmural infarct)
what is the pathophysiology of atherosclerosis?
1) Chronic stress on the endothelium
2) Endothelial dysfunction, which leads to
- -Invasion of inflammatory cells (mainly monocytes and lymphocytes) through the disrupted endothelial barrier
- -Adhesion of platelets to the damaged vessel wall → platelets release inflammatory mediators (e.g., cytokines) and platelet-derived growth factor (PDGF)
- -PDGF stimulates migration and proliferation of smooth muscle cells (SMC) in the tunica intima and mediates differentiation of fibroblasts into myofibroblasts
3) Inflammation of the vessel wall
4) Macrophages and SMCs ingest cholesterol from oxidized LDL and transform into foam cells.
5) Foam cells accumulate to form fatty streaks (early atherosclerotic lesions).
6) Lipid-laden macrophages and SMCs produce extracellular matrix (e.g., collagen) → development of a fibrous plaque (atheroma)
7) Inflammatory cells in the atheroma (e.g., macrophages) secrete matrix metalloproteinases → weakening of the fibrous cap of the plaque due to the breakdown of extracellular matrix → minor stress ruptures the fibrous cap
8) Plaque rupture → exposure of thrombogenic material (e.g., collagen) → thrombus formation with vascular occlusion or spreading of thrombogenic material
what substance stimulates migration and proliferation of smooth muscle cells (SMC) in the tunica intima and mediates the differentiation of fibroblasts into myofibroblasts?
PDGF!!!!!!
what are the foam cells?
acrophages and SMCs ingest cholesterol from oxidized LDL and transform into foam cells.
what is the fibrous plaque?
An atherosclerotic lesion comprised of lipids, connective tissue, leukocytes, and cellular debris that can develop within artery walls in the presence of certain risk factors (e.g., smoking, diabetes, hypertension, dyslipidemia). Complications include vessel obstruction and ischemia, coronary heart disease, peripheral artery disease, and thrombosis when plaque rupture occurs.
