Ischemia and Infarction

Ischemia is the reduction or interruption of blood supply to a tissue, depriving it of oxygen and metabolic substrates and impairing the clearance of waste. Infarction is the tissue death (necrosis) that results when ischemia is severe and prolonged enough to overwhelm the cell's capacity to survive. Together they represent the central consequence of obstructed or inadequate perfusion in hemodynamic disturbance.

Definition

Ischemia is a state of insufficient blood flow to a tissue relative to its metabolic demand, producing oxygen and nutrient deprivation; infarction is the localized area of ischemic necrosis that results when the deprivation is severe and sustained.

Scope

The entry covers the supply-demand basis of ischemia, the determinants of whether ischemia remains reversible or progresses to infarction, and the morphology of infarcts (red versus white). It is a general-pathology topic that explains how loss of perfusion injures tissue; it is not clinical guidance on managing any specific ischemic event.

Core questions

• What determines whether a tissue's blood supply is adequate-how do oxygen supply and demand interact?
• Why does brief ischemia produce reversible injury while prolonged ischemia produces infarction?
• Which factors influence the size and severity of an infarct, such as collateral supply and vulnerability of the tissue?
• What distinguishes a red (hemorrhagic) infarct from a white (anemic) infarct?

Key concepts

• Oxygen supply-demand mismatch
• Reversible versus irreversible cell injury
• Coagulative necrosis
• Red (hemorrhagic) versus white (anemic) infarct
• Collateral circulation
• Watershed (border-zone) ischemia
• Myocardial infarction (universal definition)
• Tissue vulnerability to hypoxia

Mechanisms

Ischemia deprives cells of oxygen and substrates, forcing a shift to anaerobic metabolism, depleting ATP, and impairing the ion pumps that maintain cellular homeostasis; intracellular calcium and reactive species rise, and cell swelling and acidosis follow. If perfusion is restored quickly, this injury can be reversible. When deprivation is severe and prolonged, irreversible injury and cell death supervene, producing an infarct-classically coagulative necrosis in most solid organs. Whether ischemia progresses to infarction depends on the rate and completeness of vascular occlusion, the availability of collateral supply, the metabolic demand and intrinsic vulnerability of the tissue, and the oxygen content of the blood. Infarcts in tissues with dual or anastomotic circulation may be hemorrhagic (red), whereas those in organs with end-arterial supply tend to be anemic (white). These mechanisms are described in pathology references and in reviews of ischemia and ischemia-reperfusion.

Clinical relevance

Ischemia and infarction underlie major disease processes including myocardial infarction and ischemic stroke, and recognizing their tissue patterns is central to pathology. The fourth universal definition of myocardial infarction provides a standardized framework for what constitutes myocardial infarction in clinical and research settings. This entry describes the underlying mechanisms at a reference level and is not a basis for diagnosing or treating any individual.

Evidence & guidelines

The mechanistic account draws on standard pathology texts and on reviews of ischemia and ischemia-reperfusion biology. For the specific case of the heart, the fourth universal definition of myocardial infarction is the consensus reference defining and classifying myocardial infarction.

History

The morphological understanding of infarction as localized ischemic necrosis was established in classical pathology and refined through the twentieth century with study of myocardial and cerebral infarction. More recent work has clarified the molecular events of oxygen deprivation and the contribution of reperfusion to final injury, while consensus statements such as the universal definition of myocardial infarction have standardized terminology.

Seminal works

• thygesen-2019
• eltzschig-2011

Frequently asked questions

What is the difference between ischemia and infarction?

Ischemia is inadequate blood flow that deprives a tissue of oxygen and nutrients and may be reversible; infarction is the actual death of tissue (necrosis) that results when ischemia is severe and prolonged.

Why are some infarcts red and others white?

Red (hemorrhagic) infarcts occur in tissues with dual or collateral blood supply or after reperfusion, allowing blood to seep into the necrotic area, while white (anemic) infarcts occur in solid organs with end-arterial supply where no such inflow exists.