lecture 9 Flashcards
pathogenesis definition
the process by which a disease or disorder develops. patho=disease, genesis = origin.
what is atheroscelorosis?
- fatty streaks leads to plaques build up
- aetiology not fully understood
- Very slow development
- Can be asymptomatic for many years
- Biggest killer in Western World!
- May affect any artery
causes ؞ Heart attack and stroke
age, lifestyle is risk factor
what is this?
atherosclerosis in large arteries (aorta)
a= mild atherosclerotic plaque, with an arrow pointing to an early lesion where lipid deposition and plaque formation have begun.b=advanced atherosclerosis with large, irregular, calcified plaques and ulcerations. These plaques have likely caused significant narrowing of the artery lumen and may have progressed to complicated lesions that could lead to thrombosis or rupture.
Pathogenesis of Atherosclerosis:
Initial Damage: Atherosclerosis begins with endothelial injury, which can be caused by factors like high LDL cholesterol, smoking, hypertension, or inflammation.
Lipid Accumulation: LDL cholesterol particles accumulate in the arterial wall and become oxidized. Monocytes adhere to the damaged endothelium, migrate into the intima, and differentiate into macrophages.
Foam Cells: Macrophages engulf oxidized lipids and become foam cells, which form fatty streaks in the arterial wall.
Smooth Muscle Activation: Growth factors such as PDGF (released by macrophages and platelets) stimulate smooth muscle cell proliferation and migration into the intima, leading to collagen and glycoprotein synthesis, further contributing to plaque formation.
Plaque Formation: The plaque develops through the accumulation of smooth muscle cells, foam cells, and extracellular matrix, leading to arterial narrowing
what is this?
- histological section showing an atherosclerotic plaque in a large artery, such as the coronary artery
- L: Refers to the lumen of the artery, the space through which blood flows. In this case, the lumen is narrowed due to the presence of the atherosclerotic plaque.
F: Refers to the fibrous cap, which is composed of smooth muscle cells, collagen, and extracellular matrix. This cap covers the atherosclerotic core and provides some structural stability to the plaque.
C: Represents the necrotic core of the plaque, which contains cholesterol crystals, lipid debris, and dead cells.
This section illustrates the typical features of an advanced atherosclerotic plaque with a lipid core and a fibrous cap. The narrowing of the lumen (L) due to plaque formation compromises blood flow, increasing the risk of ischemic events like myocardial infarction (heart attack).
Pathogenesis of Essential Hypertension:
Sustained elevation in blood pressure without an obvious cause, known as essential hypertension, affects the majority of hypertensive patients.
Mechanisms Involved:
Sodium retention: Increased sodium levels lead to water retention, increasing blood volume and cardiac output.
Sympathetic activity: Increased sensitivity to catecholamines raises heart rate and peripheral vascular resistance (PVR).
Renin-angiotensin-aldosterone system (RAAS): RAAS activation increases PVR and blood volume, raising blood pressure
Manifestations of Essential Hypertension:
Increased risk for:
Atherosclerosis
Intracerebral hemorrhage
Left ventricular hypertrophy (due to increased workload on the heart)
Heart failure
Vascular Changes:
Hyaline vascular change (homogeneous thickening of vessel walls due to leakage of plasma proteins into the vessel walls)
Myocardial Changes in Myocardial Infarction (MI):
Coagulative necrosis: Occurs due to the ischemic death of cardiac tissue, typically 30-40 minutes after occlusion.
Pallor: The myocardium becomes pale due to the lack of blood flow.
Inflammation: Neutrophils infiltrate the tissue within 1-3 days.
Fibrosis: Over time (weeks), the damaged area heals by scar formation, resulting in fibrous tissue
what does this show?
These stages illustrate the body’s response to myocardial injury, from acute necrosis to chronic scar formation, which can compromise the heart’s ability to pump efficiently.
Day 1: Coagulative necrosis with wavy fibers.
3-4 Days: Hyperemia and neutrophil infiltration.
7-10 Days: Granulation tissue starts forming.
Weeks later: Fibrous scar tissue replaces the necrotic myocardium
Management of MI (myocardial injury)
Increase oxygen supply: Through oxygen therapy and coronary reperfusion strategies (like thrombolytics or angioplasty).
Decrease oxygen demand: By using medications such as beta-blockers and nitrates.
Pain relief: Using morphine or other analgesics to manage chest pain.
Prevent arrhythmias: Using anti-arrhythmic drugs.
Treat the underlying cause: By administering thrombolytics (e.g., streptokinase), angioplasty, or bypass surgery
