Cell Liquefactive Necrosis

Cells maintain their structure and function by adapting to environmental changes. However, when subjected to severe stress, exposure to harmful agents, or intrinsic defects, cells may reach a threshold where adaptation is no longer possible, leading to cell injury. This process involves various cellular and metabolic disruptions and can follow a trajectory from reversible injury to irreversible damage and cell death. In the early or mild stages of injury, cellular damage remains reversible if the stressor is removed. Although there may be noticeable structural and functional impairments during this phase, the cell retains the capacity to recover and restore normal function. This stage is characterized by alterations in metabolic pathways and organelles without permanent loss of cell viability. If the harmful stimulus persists, the damage may progress beyond the point of repair, resulting in irreversible injury and ultimately cell death. These stages are central to understanding the cellular responses to various pathological conditions. Irreversible injury to cells due to encounters with noxious stimuli invariably leads to cell death. Such noxious stimuli include infectious agents (bacteria, viruses, fungi, parasites), oxygen deprivation or hypoxia, and extreme environmental conditions such as heat, radiation, or exposure to ultraviolet irradiation. The resulting death is known as necrosis, a term usually distinguished from the other major consequences of irreversible injury, known as cell death by apoptosis. Apoptosis is a programmed or organized cell death that could be physiological or pathological. Additional information regarding this form of cell death is outside this chapter's scope. Necrosis, a cell death, is almost always associated with a pathological process. When cells die by necrosis, they exhibit 2 major types of microscopes or macroscopic appearance. The first is liquefactive necrosis, also known as colliquative necrosis, which is characterized by partial or complete dissolution of dead tissue and transformation into a liquid, viscous mass. The loss of tissue and cellular profile occurs within hours in liquefactive necrosis. In contrast to liquefactive necrosis, coagulative necrosis, the other major pattern, is characterized by maintaining normal architecture of necrotic tissue for several days after cell death. Liquefaction derives from the slimy, liquid-like nature of tissues undergoing liquefactive necrosis. This morphological appearance is partly attributable to hydrolytic enzymes' activities, which cause the dissolution of cellular organelles in a necrosis cell. The enzymes responsible for liquefaction are derived from bacterial or lysosomal hydrolytic enzymes. In addition to liquefactive and coagulative necrosis, the other morphological patterns associated with cell death by necrosis are: Caseous Necrosis. Fat Necrosis. Gangrenous Necrosis. Fibrinoid Necrosis. The other types of necrosis listed above do not represent distinct pathological entities. Rather, they are descriptive terms widely used to describe necrosis occurring in specific clinical scenarios or organ damage. This is the default pattern of necrosis associated with ischemia or hypoxia in every organ except the brain. Gross Appearance: Tissue is firm, and architecture is maintained for days after cell death. Microscopic: Preserved cell outlines without nuclei. The pattern of necrosis is seen with infections. Also, the pattern is seen following ischemic injury in the brain. While the reason for liquefactive necrosis following ischemic injury in the brain is poorly understood, the release of digestive enzymes and constituents of neutrophils is the reason for liquefaction in infections. Gross Appearance: The tissue is liquid and sometimes creamy yellow because of pus formation. Microscopic: Inflammatory cells with numerous neutrophils. A unique type of cell death is seen with tuberculosis. Gross Appearance: White, soft, cheesy-looking (caseating) material. Microscopic: A uniformly eosinophilic center (necrosis) surrounded by a collar of lymphocytes and activated macrophages (giant cells, epithelioid cells): The entire structure formed in response to tuberculosis is known as a granuloma. Fat necrosis occurs from acute inflammation affecting tissues with numerous adipocytes, such as pancreas and breast tissue. Damaged cells release digestive enzymes, which break down lipids to generate free fatty acids. Gross Appearance: Whitish deposits as a result of the formation of calcium soaps. Microscopic: Anucleated adipocytes with calcium deposits (seen on H&E as areas of bluish stains). This is a pattern associated with vascular damage (autoimmunity, immune-complex deposition, infections (viruses, spirochetes, rickettsiae). Gross Appearance: Usually not grossly discernible. Microscopic: Deposition of fibrin within blood vessels. Clinically, this describes ischemic necrosis of the lower limbs (sometimes upper limbs or digits). Gross Appearance: Black skin with varying degrees of putrefaction. Microscopic: Combination of coagulative necrosis due to ischemia (dry gangrene); and liquefactive necrosis (wet gangrene) if a bacterial infection is superimposed. These represent morphological patterns that are visible grossly and microscopically. Fibrinoid necrosis is usually visible only microscopically. In subsequent paragraphs, we discuss the gross and microscopic findings in liquefactive necrosis.