Journal of Clinical & Experimental Pathology
Open Access

Necrosis is a type of cell death that occurs when external forces cause irreversible harm to the cells. It is a pathological process that differs from apoptosis, which is a programmed, regulated cell death mechanism. Trauma, illness, toxins, ischemia (inadequate blood supply), and other adverse stressors can all cause necrosis. This cell death results in the uncontrolled loss of cellular components, which triggers inflammatory reactions in surrounding tissues, frequently contributing to tissue damage and disease progression. Necrosis is the premature, uncontrolled death of cells and living tissue. It is usually caused by a lack of oxygen, a physical injury, chemical drugs, or an infection. When necrosis occurs, the cell membrane degrades, allowing the contents of the cell to be released uncontrollably into the extracellular environment. Necrotic cells enlarge, burst, and spill their contents into the surrounding tissue, causing irritation. Necrosis's inflammation can cause more harm to neighboring healthy tissues, which is why necrosis is frequently linked to acute or chronic injury in a variety of disorders.

Ischemia, or the lowering or cessation of blood supply to tissues, is the most prevalent cause of necrosis. This frequently occurs in the context of myocardial infarction (heart attack), stroke, and peripheral artery disease. Exposure to hazardous substances, whether from the environment or pathogens (for example, bacterial toxins), can impair cellular metabolism and membrane integrity, resulting in necrosis. Burns frostbite, and mechanical injuries can all induce cellular damage and necrosis. Once necrosis begins, the loss of cell membrane integrity is a distinguishing trait. As the plasma membrane becomes permeable, cellular contents such as enzymes and organelles are released into the extracellular environment, resulting in an inflammatory reaction. The most prevalent kind is coagulative necrosis, which occurs in tissues that have been ischemic, particularly the heart, kidney, and spleen. The architecture of dead tissue is retained for a few days due to protein denaturation, including enzymes that would ordinarily breakdown the dead cells. This makes the necrotic tissue stiff and opaque. Over time, inflammatory cells destroy necrotic tissue, which is replaced by scar tissue.

Liquefactive necrosis occurs when hydrolytic enzymes digest dead cells, producing a liquid mass. It is most commonly seen in the brain because of the high concentration of lipid-rich tissues, as well as in abscesses where bacterial infection causes fluid to accumulate. The tissue softens and liquefies as the cells decompose, leaving cystic divisions behind. Caseous necrosis, a combination of coagulative and liquefactive necrosis, is associated with tuberculosis and certain fungal infections. Fat necrosis occurs when lipase enzymes break down fat cells, releasing fatty acids that mix with calcium to form chalky deposits. This form of necrosis is typically seen in acute pancreatitis, which occurs when the pancreas' digestive enzymes are triggered, resulting in autodigestion of the surrounding fatty tissue. It can also appear in subcutaneous fat tissue following trauma. Fibrinoid necrosis is defined by the deposition of fibrin-like material in the inner walls of blood vessels, resulting in a bright pink, amorphous appearance under the microscope. This type of necrosis is common in immune-mediated diseases such as vasculitis, in which immune complexes and plasma proteins leak into and destroy the vessel wall.

While necrosis is commonly seen as an unregulated process, recent research indicates that certain types of necrosis, such as necroptosis, involve specific signals. Necroptosis is a type of necrosis that is regulated by proteins such as Receptor-Interacting Serine/Threonine- Protein Kinase 1 (RIPK1) and Receptor-Interacting Serine/Threonine- Protein Kinase 3 (RIPK3) and mixed lineage kinase domain-like protein. Death receptors, including as Tumor Necrosis Factor (TNF) and Toll-like receptors, can activate this mechanism. Unlike apoptosis, which uses caspases, necroptosis causes cell membrane rupture and inflammation. The therapy of necrosis is mostly determined by its fundamental etiology. Restoring blood flow in ischemic circumstances such as myocardial infarction or stroke is essential for limiting necrosis. This can be accomplished through medical procedures such as clot-dissolving medicines, angioplasty, or surgical bypass. Antibiotics and surgical treatment (dead tissue removal) are frequently used to treat infection-induced necrosis. Finally, necrosis is a pathological phase of cell death that involves the loss of membrane integrity, the release of intracellular contents, and subsequent inflammation. It is important in the progression of many diseases, including myocardial infarction and cancer. While necrosis is often thought to be unregulated, recent research of mechanisms such as necroptosis point to a more complex process with possible new treatment options.