Morphologic types of necrosis (cell death in living tissue, often with an inflamma-tory response) are as follows:
· Coagulative necrosis, the most common form of necrosis, is most often due toischemic injury (infarct). It is caused by the denaturing of proteins within the cytoplasm. Microscopic examination shows loss of the nucleus but preservation of cellular shape. Coagulative necrosis is common in most organs, including the heart, liver, and kidney, but not the brain.
· Liquefaction necrosis results from cellular destruction by hydrolytic enzymes,leading to autolysis (release of proteolytic enzymes from injured cells) and het-erolysis (release of proteolytic enzymes from inflammatory cells). Liquefaction necrosis occurs in abscesses, brain infarcts, and pancreatic necrosis.
· Caseous necrosis is a combination of coagulation and liquefaction necrosis. Thegross appearance is soft, friable, and “cheese-like.” Caseous necrosis is charac-teristic of granulomatous diseases, including tuberculosis.
· Fat necrosis is caused by the action of lipases on adipocytes and is characteris-tic of acute pancreatitis. On gross examination fat necrosis has a chalky white appearance.
· Fibrinoid necrosis is a form of necrotic connective tissue that histologicallyresembles fibrin. On microscopic examination fibrinoid necrosis has an eosin-ophilic (pink) homogeneous appearance. It is often due to acute immunologic injury (e.g., hypersensitivity type reactions II and III) and vascular hyperten-sive damage.
· Gangrenous necrosis is a gross term used to describe dead tissue. Commonsites of involvement include lower limbs, gallbladder, GI tract, and testes. Dry gangrene has coagulative necrosis for the microscopic pattern, while wet gan-grene has liquefactive necrosis.
Apoptosis is a specialized form of programmed cell death without an inflammatoryresponse. It is an active process regulated by proteins that often affects only single cells or small groups of cells
· In morphologic appearance, the cell shrinks in size and has dense eosino-philic cytoplasm. Next, nuclear chromatin condensation (pyknosis) is seen that is followed by fragmentation of the nucleus (karyorrhexis). Cytoplasmic membrane blebs form next, leading eventually to a breakdown of the cell into fragments (apoptotic bodies). Phagocytosis of apoptotic bodies is by adjacent cells or macrophages.
· Stimuli for apoptosis include cell injury and DNA damage, lack of hor-mones, cytokines, or growth factors, and receptor-ligand signals such as Fas binding to the Fas ligand and tumor necrosis factor (TNF) binding to TNF receptor 1 (TNFR1).
· Apoptosis is regulated by proteins. The protein bcl-2 (which inhibits apopto-sis) prevents release of cytochrome c from mitochondria and binds pro-apop-totic protease activating factor (Apaf-1). The protein p53 (which stimulates apoptosis) is elevated by DNA injury and arrests the cell cycle. If DNA repair is impossible, p53 stimulates apoptosis.
· Execution of apoptosis is mediated by a cascade of caspases (cysteine asparticacid proteases). The caspases digest nuclear and cytoskeletal proteins and also activate endonucleases.
· Physiologic examples of apoptosis include embryogenesis (organogenesisand development), hormone-dependent apoptosis (menstrual cycle), thymus (selective death of lymphocytes).
· Pathologic examples of apoptosis include viral diseases (viral hepatitis [Coun-cilman body]), graft-versus-host disease, and cystic fibrosis (duct obstruction and pancreatic atrophy).
Serum enzyme markers of cell damage include aspartate aminotransferase (AST)(liver injury), alanine aminotransferase (ALT) (liver injury), creatine kinase (CK-MB) (heart injury), and amylase and lipase (pancreatic injury; amylase also rises with salivary gland injury).