INFARCTION

An infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue. Tissue infarction is a common and extremely important cause of clinical illness. More than half of all deaths in the United States are caused by cardiovascular disease, and most of these are attributable to myocardial or cerebral infarction. Pulmonary infarction is a common complication in several clinical settings, bowel infarction is frequently fatal, and ischemic necrosis of the extremities (gangrene) is a serious problem in the diabetic population.

Nearly 99% of all infarcts result from thrombotic or embolic events, and almost all result from arterial occlusion. Occasionally, infarction may also be caused by other mechanisms, such as local vasospasm, expansion of an atheroma secondary to intraplaque hemorrhage, or extrinsic compression of a vessel (e.g., by tumor). Uncommon causes include vessel twisting (e.g., in testicular torsion or bowel volvulus), vascular compression by edema or entrapment in a hernia sac, or traumatic vessel rupture. Although venous thrombosis can cause infarction, it more often merely induces venous obstruction and congestion. Usually, bypass channels open rapidly after the occlusion forms, providing some outflow from the area that, in turn, improves the arterial inflow. Infarcts caused by venous thrombosis are more likely in organs with a single venous outflow channel (e.g., testis and ovary).

Morphology

Infarcts are classified on the basis of their color (reflecting the amount of hemorrhage) and the presence or absence of microbial infection. Therefore, infarcts may be either red (hemorrhagic) or white (anemic) and may be either septic or bland.

Red infarcts (Fig. 4-18A) occur (1) with venous occlusions (such as in ovarian torsion); (2) in loose tissues (such as lung) that allow blood to collect in the infarcted zone; (3) in tissues with dual circulations such as lung and small intestine, permitting flow of blood from an unobstructed parallel supply into a necrotic area (such perfusion not being sufficient to rescue the ischemic tissues); (4) in tissues that were previously congested because of sluggish venous outflow; (5) when flow is re-established to a site of previous arterial occlusion and necrosis (e.g., fragmentation of an occlusive embolus or angioplasty of a thrombotic lesion).

White infarcts occur with arterial occlusions or in solid organs (such as heart, spleen, and kidney), where the solidity of the tissue limits the amount of hemorrhage that can seep into the area of ischemic necrosis from adjoining capillary beds (Fig. 4-18B).

All infarcts tend to be wedge shaped, with the occluded vessel at the apex and the periphery of the organ forming the base (see Fig. 4-18); when the base is a serosal surface there can be an overlying fibrinous exudate. At the outset, all infarcts are poorly defined and slightly hemorrhagic. The margins of both types of infarcts tend to become better

defined with time by a narrow rim of congestion attributable to inflammation at the edge of the lesion.

In solid organs, the relatively few extravasated red cells are lysed, with the released hemoglobin remaining in the form of hemosiderin. Thus, infarcts resulting from arterial occlusions typically become progressively more pale and sharply defined with time (see Fig. 4-18B). In spongy organs, by comparison, the hemorrhage is too extensive to permit the lesion ever to become pale (see Fig. 4-18A). Over the course of a few days, however, it does become firmer and browner, reflecting the accumulation of hemosiderin pigment.

The dominant histologic characteristic of infarction is ischemic coagulative necrosis (Chapter 1). An inflammatory response begins to develop along the margins of infarcts within a few hours and is usually well defined within 1 to 2 days. Eventually the inflammatory response is followed by a reparative response beginning in the preserved margins (Chapter 3). In stable or labile tissues, parenchymal regeneration can occur at the periphery, where underlying stromal architecture is spared. However, most infarcts are ultimately replaced by scar (Fig. 4-19). The brain is an exception to these generalizations; ischemic tissue injury in the central nervous system results in liquefactive necrosis (Chapter 1).

Septic infarctions occur when bacterial vegetations from a heart valve embolize or when microbes seed an area of necrotic tissue. In these cases the infarct is converted into an abscess, with a correspondingly greater inflammatory response (Chapter 2). The eventual sequence of organization, however, follows the pattern previously described.

Figure 4-18 Red and white infarcts. A, Hemorrhagic, roughly wedge-shaped pulmonary infarct (red infarct). B, Sharply demarcated pale infarct in the spleen (white infarct).

Figure 4-19 Remote kidney infarct, now replaced by a large fibrotic scar.Factors That Influence Development of an Infarct

Vascular occlusion can have no or minimal effect, or can cause death of a tissue or even the individual. The major determinants of the eventual outcome include the nature of the vascular supply, the rate of development of the occlusion, vulnerability to hypoxia, and the oxygen content of blood.

Nature of the Vascular Supply

The availability of an alternative blood supply is the most important determinant of whether occlusion of a vessel will cause damage. For example, as mentioned above, lungs have a dual pulmonary and bronchial artery blood supply; thus, obstruction of small pulmonary arterioles does not cause infarction in an otherwise healthy individual with an intact bronchial circulation. Similarly, the liver, with its dual hepatic artery and portal vein circulation, and the hand and forearm, with their dual radial and ulnar arterial supply, are all relatively resistant to infarction. In contrast, renal and splenic circulations are end-arterial, and obstruction of such vessels generally causes infarction.

Rate of Development of Occlusion

Slowly developing occlusions are less likely to cause infarction because they provide time for the development of alternative perfusion pathways. For example, small interarteriolar anastomoses-normally with minimal functional flow-interconnect the three major coronary arteries in the heart. If one of the coronaries is slowly occluded (e.g., by an encroaching atherosclerotic plaque), flow within this collateral circulation may increase sufficiently to prevent infarction, even though the major coronary artery is eventually occluded.

Vulnerability to Hypoxia

The susceptibility of a tissue to hypoxia influences the likelihood of infarction. Neurons undergo irreversible damage when deprived of their blood supply for only 3 to 4 minutes. Myocardial cells, though hardier than neurons, are also quite sensitive and die after only 20 to 30 minutes of ischemia. In contrast, fibroblasts within myocardium remain viable after many hours of ischemia.

Oxygen Content of Blood

The partial pressure of oxygen in blood also determines the outcome of vascular occlusion. Partial flow obstruction of a small vessel in an anemic or cyanotic patient might lead to tissue infarction, whereas it would be without effect under conditions of normal oxygen tension. In this way congestive heart failure, with compromised flow and ventilation, could cause infarction in the setting of an otherwise inconsequential blockage.

SUMMARY

Infarction Infarcts are areas of ischemic, usually coagulative, necrosis caused by occlusion of arterial supply or less commonly venous drainage.Infarcts are most commonly caused by formation of occlusive arterial thrombi, or embolization of arterial or venous thrombi.Infarcts caused by venous occlusion, or in loose tissues with dual blood supply, are typically hemorrhagic (red) whereas those caused by arterial occlusion in compact tissues are pale (white) in color.