Cell injury occurs due to decreased generation of cellular ATP ATP is necessary for Na+--K+ ATPase pump and Ca pump action and many other cellular functions for the existence of the cell THE MORPHOLOGY OF CELL AND TISSUE INJURY It is useful to describe the structural alterations that occur in damaged cells before we discuss the biochemical mecha- nisms that bring about these changes. All stresses and noxious influences exe their effects first at the molecular or biochemical level. Cellular function may be lost long before cell death occurs, and the morphologic changes of cell injury (or death) lag far behind both (Fig. 1-7). For example, myocardial cells become noncontractile after 1 to 2 minutes of isch- emia, although they do not die until 20 to 30 minutes of ischemia have elapsed. These myocytes may not appear dead by electron microscopy for 2 to 3 hours, or by light microscopy for 6 to 12 hours. The cellular derangements of reversible injury can be corrected, and if the injurious stimulus abates, the cell can return to normalcy. Persistent or excessive injury, however, causes cells to pass the nebulous "point of no return" into irreversible injury and cell death. The events that determine when reversible injury becomes irreversible and progresses to cell death remain poorly understood. The clinical rele- vance of this question is obvious; if the biochemical and molecular changes that predict cell death can be identified with precision, it may be possible to devise strategies for preventing the transition from reversible to irreversible cell injury. Although there are no definitive morphologic or biochemical correlates of irreversibility, two phenomena con- sistently characterize irreversibility: the inability to correct mito- chondrial dysfunction (lack of oxidative phosphorylation and ATP generation) even after resolution of the original injury, and profound disturbances in membrane function. As mentioned earlier, injury to lysosomal membranes results in the enzymatic dissolution of the injured cell, which is the culmination of injury progressing to necrosis. As mentioned earlier, different injurious stimuli may induce death by necrosis or apoptosis (Fig. 1-6 and Table Refer robbins 9/e p6