Pathology Flashcards
Ischemic Heart Disease
- Leading cause of death worldwide for both men and women
- group of pathophysiologically related syndromes resulting from myocardial ischemia-
- imbalance b/t the supply and demand of the heart for O2
- insufficient of O2 & reduced availability of nutrients & removal of metabolites and less tolerated than pure hypoxia,
- more than 90% caused by reduced blood flow due to obstructive atherosclerotic lesions in the coronary arteries.
- often termed coronary artery disease (CAD) or coronary heart disease.
IHD Pathogenesis
- > 90% have atherosclerosis of one or more coronary arteries.
- generally due to narrowing of the lumen leading to stenosis (“fixed” obstructions)
- or acute plaque disruption with thrombosis
- fixed lesion obstructing 75% or greater of the lumen is generally required to cause symptomatic ischemia precipitated by exercise (most often manifested angina);
- compensatory coronary arterial vasodilation is no longer sufficient to meet even small increases in myocardial demand
- Obstruction of 90% of the lumen can lead to inadequate coronary blood flow even at rest.
- progressive ischemia induced may stimulate the formation of collateral vessels over time, which can protect against myocardial ischemia and infarction
3 Types of Angina Pectoris
- Stable angina: most common form
- caused by an imbalance in coronary perfusion (due to chronic stenosing coronary atherosclerosis) relative to demand
- produced by physical activity, emotional excitement, or any other cause of increased cardiac workload.
- usually relieved by rest decreases demand) or administering nitroglycerin, a strong vasodilator (increases perfusion).
- Prinzmetal variant angina: uncommon from of episodic myocardial ischemia
- caused by coronary artery spasm.
- unrelated to physical activity, heart rate, or blood pressure.
- generally responds promptly to vasodilators, such as nitroglycerin and calcium channel blockers.
- Unstable or crescendo angina: pattern of increasingly frequent pain, often of prolonged duration
- precipitated by progressively lower levels of physical activity or that even occurs at rest.
- caused by the disruption of an atherosclerotic plaque with superimposed partial (mural) thrombosis and possibly embolization or vasospasm (or both).
- warning that an acute MI may be imminent
MYOCARDIAL INFARCTION Pathogenesis
- death of cardiac muscle due to prolonged severe ischemia.
- most important form of IHD.
- Coronary Arterial Occlusion
- sequence of events
- 1st: sudden change in an atheromatous plaque: intraplaque hemorrhage, erosion or ulceration, or rupture or fissuring.
- exposed to subendothelial collagen and necrotic plaque contents, platelets adhere, become activated, release their granule contents, and aggregate to form microthrombi.
- Vasospasm stimulated by mediators from platelets
- Tissue factor activates the coagulation pathway, adding to the bulk of the thrombus.
- within minutes, thrombus evolves to completely occlude the lumen of the vessel.
- Other causes:
- Vasospasm with or without coronary atherosclerosis: association with platelet aggregation or due to cocaine abuse
- Emboli from the left atrium in association with
- atrial fibrillation
- a left-sided mural thrombus
- vegetations of infective endocarditis,
- intracardiac prosthetic material
- paradoxical emboli from veins through a patent foramen ovale to the coronary arteries
- W/O atherosclerosis:
- vasculitis
- hematologic abnormalities such as sickle cell disease
- amyloid deposition in vascular walls
- vascular dissection
- lowered systemic blood pressure (shock);
- inadequate myocardial “protection” during surgery
MI Complications
-Contractile dysfunction:
*abnormalities in left ventricular function w/ some degree of left ventricular failure
*pulmonary edema and respiratory impairment.
*cardiogenic shock occurs in 10% to 15% of patients
-Myocardial rupture:
*from softening and weakening of the necrotic and inflamed myocardium.
*rupture of the ventricular free wall with hemopericardium and cardiac tamponade
-most frequent 3 to 7 days after MI
*rupture of the ventricular septum, leading to an acute VSD and left-to-right shunting
*papillary muscle rupture, resulting in the acute onset of severe mitral regurgitation
-Pericarditis: develops about 2nd or 3rd day after transmural infarct as a result of underlying myocardial inflammation
-Right ventricular infarction cause acute right-sided heart failure associated with pooling of blood in the venous circulation and systemic hypotension.
-Infarct extension: New necrosis may occur adjacent to an existing infarct.
-Infarct expansion. As a result of the weakening of necrotic muscle, there may be disproportionate stretching, thinning, and dilation of the infarct region
-Mural thrombus: abnormality in contractility (causing stasis) and endocardial damage (creating a thrombogenic surface) can foster mural thrombosis and potentially thromboembolism
-Ventricular aneurysm: bounded by myocardium that has become scarred.
*late complication of large transmural infarcts that experience early expansion.
-Papillary muscle dysfunction: ischemic dysfunction of a papillary muscle & later from papillary muscle fibrosis and shortening, or from ventricular dilation
Progressive late heart failure
MI Diagnosis
-laboratory evaluation of MI is based on measuring the blood levels of proteins that leak out of fatally injured myocytes
*myoglobin
*cardiac troponins T and I
*MB fraction of creatine kinase (CK-MB)
*lactate dehydrogenase
-these cardiac biomarkers are increased in the clinical setting of acute ischemia
-most sensitive and specific biomarkers of myocardial damage are cardiac-specific proteins, particularly Troponins I and T
(proteins that regulate calcium-mediated contraction of cardiac and skeletal muscle).
-Troponins I and T are not normally detectable in the circulation.
-Following an MI, levels of both begin to rise at 2 to 4 hours and peak at 48 hours
-elevated troponin levels persist for approximately 7 to 10 days after acute MI, well after CK-MB levels have returned to normal
Rheumatic fever
- acute, immunologically mediated, multisystem inflammatory disease that occurs a few weeks after an episode of group A streptococcal pharyngitis.
- RF may progress over time to chronic rheumatic heart disease
- valvular abnormalities are key manifestations.
- characterized by deforming fibrotic valvular disease, particularly mitral stenosis
- incidence and mortality have declined due to improved conditions and rapid diagnosis/treatment of strep pharyngitis
- Aschoff bodies, which consist of foci of lymphocytes (primarily T cells), occasional plasma cells, and plump activated macrophages called Anitschkow cells (pathognomonic for RF).
- abundant cytoplasm and central round-to-ovoid nuclei in which the chromatin is disposed in a central, slender, wavy ribbon (“caterpillar cells”), and may become multinucleated.
Hypertension
-Defined as BP>140/90
Normal 160/>100
-Risk factors: age, obesity, diabetes, smoking, genetic
-black>white>asians
-Features: 90% is essential
*related to increased CO or TPR (increased Na+ retention)
-10% secondary to renal disease & others
-Malignant HTN is severe and rapidly progressing
-Complications: atherosclerosis, LV hypertrophy, stroke, CHF, renal failure, retinopathy, and aortic dissection
Arteriosclerosis
- Monckeberg: calcification in the media of arteries, especially radial or ulnar; usually benign
- ‘pipestem’ arteries
- does no obstruct flow, intima NOT involved
- Arteriolosclerosis: Hyalin thickening of small arteries in essential HTN, diabetes mellitus
- Hyperplastic “onion skinning” occurs in malignant HTN
- Atherosclerosis: fibrous plaques and atheromas form in intima or arteries
Atherosclerosis
- Disease of elastic arteries and large/medium muscular arteries
- Risk factors: smoking, HTN, DM, hyperlipidemia, family hx
- Progression: Endothelial cell dysfxn->macrophage and LDL accumulation->foam cell formation->fatty streaks->smooth muscle cell migration (PDGF & TGF-B)->fibrous plaque->complex atheromas
- Complications: aneurysms, ischemia, infarcts, peripheral, vascular disease, thrombus, emboli
- Location: abdominal aorta>coronary artery>popliteal artery>carotid artery
- Symptoms: Angina, claudication, can be asymptomatic
Aortic Aneurysms
- Localized pathologic dilation of blood vessel
- Abdominal aortic aneurysm: associated w/ atherosclerosis
- occurs more often in males than females, >50yrs
- Thoracic aortic aneurysm: associated w/ HTN and Marfan’s
Aortic Dissection
- Associated w/ HTN, Marfan’s
- Presents w/ tearing chest pain radiating to the back
- CXR shows mediastinal widening
- False lumen occupies most of the descending aorta
- can result in aortic rupture and death
Ischemic Heart Disease: Possible Manifestations
- Angina (CAD narrowing >75%)
- Stable: secondary to atherosclerosis; ST depression & retrosternal pain w/ exertion
- Prinzmetal’s variant: secondary to coronary artery spasm; ST elevation
- Unstable: thrombosis w/o necrosis; ST depression, chest pain at rest or minimal exertion
- Coronary Steal Syndrome: vasodilator may aggregate ischemia by shunting blood from critical stenosis to higher perfusion area
- MI: most often acute thrombosis due to coronary artery atherosclerosis
- Results in myocyte necrosis
- Sudden cardiac death: w/in 1h of symptom onset
- usually lethal arrhythmia
- Chronic Ischemic heart Disease: progressive onset of CHF over may years due to chronic ischemic myocardial damage
Evolution of MI
- 0-4h: No gross or microscopic changes; arrhythmia risk
- 4-12h: dark mottling; pale w/ tetrazolum stain
- microscopically: early coagulative necrosis, edema, hemorrhage, and wavy fibers
- Risk of arrhythmias
- 12-24h: dark mottling; pale w/ tetrazolum stain
- Microscopic contraction bands, release of necrotic cell content, beginning of neutrophil emigration
- Risk of arrhythmia
- 2-4d: Hyperemia
- Extensive coagulative necrosis: neutrophil emigration
- tissues around infarct has acute inflammation
- Risk arrhythmia
- 5-10d: hyperemic border, central yellow/brown softening
- Granulation tissue appears at margins (VEGF)
- Risk of free wall rupture, tamponade, papillary muscle rupture, IV septum rupture, b/c macrophages degrade structure
- 7wks: Recanalizated artery; gray-white
- contracted scar complete
- Risk of Ventricular aneurysm
Diagnosing MI
- First 6h: ECG os gold standard
- ST elevation: transmural infarct
- ST depression: subendocardial infarct
- Pathologic Q wave: transmural infarct
- Cardiac troponin I rises after 4h and up 7-10d
- more specific than other protein markers
- CK-MB: can also be found in skeletal muscle so less specific
- useful in diagnosing reinfarction on top of acute MI
- AST: nonspecific & can be found in cardiac, liver, and muscle
