The normal cell is a highly complex unit in which the various organelles and enzyme systems continuously carry out the metabolic activities that maintain cell viability and support its normal functions. Normal function is dependent on (1) the immediate environment of the cell; (2) a continuous supply of nutrients such as oxygen, glucose, and amino acids; and (3) constant removal of the products of metabolism, including CO2.
Injury to a cell may be nonlethal or lethal (Figure 1-1).
Mechanisms of injury leading to cell degeneration and necrosis. Individual separate mechanisms are discussed in the text.
Lethal injuries to the tissues of a living individual cause cell death (necrosis). Necrosis is accompanied by biochemical and structural changes (see below) and is irreversible. The necrotic cells cease to function; if necrosis is sufficiently extensive, clinical disease results.
Cell necrosis should be distinguished from the death of the individual, which is difficult to define. From a legal standpoint in many countries, an individual is considered dead when there is complete and irreversible cessation of brain function. Many individual cells and tissues in a legally dead individual remain viable for some time after death, however, and constitute a major source of organs for transplantation.
Nonlethal Injury (Degeneration)
Nonlethal injury to a cell may produce cell degeneration, which is manifested as some abnormality of biochemical function, a recognizable structural change, or a combined biochemical and structural abnormality. Degeneration is reversible but may progress to necrosis if injury persists. When it is associated with abnormal cell function, cell degeneration may also cause clinical disease.
Programmed Cell Death (Apoptosis)
It is worth remembering that cell degeneration and cell death are ongoing phenomena in multicellular organisms and that in the healthy state, they are balanced by cell renewal. This process, through which effete cells are removed from normal tissue, is termed apoptosis. It differs from necrosis in that apoptotic cells are rapidly removed by phagocytes and there is no overt inflammation associated with their removal. In addition, apoptosis typically is initiated within the cell by nuclear fragmentation (pyknosis) and cytoplasmic condensation. Cell membranes remain intact in the early stages, leading to small shrunken cells containing cytoplasmic or nuclear debris (apoptotic bodies). Certain growth control genes may initiate apoptosis (Chapter 18: Neoplasia: II. Mechanisms & Causes of Neoplasia) or inhibit it (bcl-2, Chapter 29: The Lymphoid System: II. Malignant Lymphomas).
Impaired Energy Production
High-energy phosphate bonds of adenosine triphosphate (ATP) represent the most efficient energy source for the cell. ATP is produced by phosphorylation of adenosine diphosphate (ADP), a reaction that is linked ...