Coronary artery disease (CAD) represents a condition where the blood vessels supplying the heart muscle become narrowed or blocked. This narrowing can reduce blood flow, limiting the oxygen and nutrients that reach the heart. Understanding pathophysiology involves examining how a disease process originates and progresses, influencing the body’s normal functions.
Endothelial Dysfunction The First Step
The innermost lining of the coronary arteries is the endothelium, a delicate single-cell layer. It plays a considerable role in maintaining vascular health by regulating blood vessel tone and preventing blood clots, ensuring smooth blood flow.
When this protective lining is damaged, it loses normal functions, a state termed endothelial dysfunction. High blood pressure, for instance, exerts stress on arterial walls, contributing to this initial injury.
Elevated low-density lipoprotein (LDL) cholesterol also contributes to endothelial damage. Toxins in tobacco smoke directly impair endothelial cell function. Similarly, persistently high blood sugar levels, characteristic of diabetes, can lead to widespread endothelial damage.
Atherosclerotic Plaque Development
Following the initial injury to the endothelium, LDL cholesterol particles begin to penetrate the damaged arterial lining. These particles accumulate within the inner wall of the artery, beneath the endothelium. This accumulation marks the first physical step in the formation of an atherosclerotic plaque.
The immune system recognizes this trapped cholesterol as foreign, initiating an inflammatory response. Monocytes are recruited to the lipid accumulation site, differentiating into macrophages—specialized immune cells that engulf foreign substances.
Macrophages consume the accumulated LDL cholesterol, transforming into lipid-laden cells known as foam cells. These foam cells are a characteristic feature of early atherosclerotic lesions. Their presence contributes to the growing fatty streak within the arterial wall.
Over time, foam cells, along with migrating smooth muscle cells, contribute to the increasing size of the plaque. This growing plaque protrudes into the artery’s lumen, gradually narrowing the passageway for blood flow. The continuous buildup of these components leads to the progressive enlargement of the atherosclerotic lesion.
Plaque Maturation and Instability
Not all atherosclerotic plaques pose the same level of immediate danger; their stability varies significantly. A stable plaque typically features a thick, robust fibrous cap, encasing the lipid-rich core. While these plaques can narrow the artery, potentially causing chest discomfort during physical exertion, their thick cap makes them less likely to rupture.
Conversely, an unstable or vulnerable plaque is highly prone to rupture. These plaques are distinguished by a thin fibrous cap that provides inadequate protection for the underlying lipid core. They also tend to have a larger lipid core and more inflammatory cells within their structure.
The thinness of the cap, combined with ongoing inflammation, renders these plaques fragile. The composition and architecture of the plaque, rather than just its size, are the primary determinants of its potential for causing acute events.
Thrombosis and Acute Coronary Events
When an unstable plaque ruptures, its thin fibrous cap tears open, exposing highly thrombogenic material within its core to the circulating blood. This exposed material, rich in lipids and tissue factor, acts as a powerful trigger for the body’s clotting mechanisms.
The body’s immediate response to this injury is the formation of a blood clot at the rupture site. Platelets quickly adhere to the exposed plaque material, forming a plug. This plug then serves as a scaffold for a more extensive fibrin mesh, which traps red blood cells and stabilizes the clot.
This newly formed thrombus can rapidly expand, obstructing the coronary artery. When blood flow to a section of the heart muscle is severely reduced or cut off by this blockage, it leads to acute coronary events. These events manifest as unstable angina, characterized by chest pain at rest, or a myocardial infarction, where heart muscle tissue dies from prolonged lack of oxygen.
Consequences for the Heart Muscle
When a coronary artery becomes significantly blocked, the heart muscle downstream experiences a severe reduction in blood flow, leading to myocardial ischemia. If this lack of oxygen persists, affected heart muscle cells begin to die. The extent of damage depends on the blocked vessel’s size and the occlusion’s duration.
Following a myocardial infarction, the damaged heart muscle undergoes cardiac remodeling. In the area where cells have died, scar tissue forms, replacing lost contractile muscle. This scar tissue is stiff and does not contribute to the heart’s pumping action.
The remaining healthy heart muscle may attempt to compensate by enlarging and changing shape. While this adaptation can temporarily maintain pumping, it often leads to a less efficient, altered heart. This long-term remodeling can progressively impair the heart’s ability to pump blood effectively, contributing to chronic conditions like heart failure.