Irreversible cell injury is indicated by
The hallmark of irreversible cell injury is a loss of integrity of cell membrane and lysosomal membranes Myelin figures are phospholipid deposits formed as a result of cell membrane integrity loss; Seen in the very late phase of reversible injury and irreversible injury. Necrosis Necrosis is the type of cell death that is associated with loss of membrane integrity and leakage of cellular contents cul- minating in dissolution of cells, largely resulting from the degradative action of enzymes on lethally injured cells. The leaked cellular contents often elicit a local host reaction, called inflammation, that attempts to eliminate the dead cells and sta the subsequent repair process (Chapter 2). The enzymes responsible for digestion of the cell may be derived from the lysosomes of the dying cells themselves and from the lysosomes of leukocytes that are recruited as pa of the inflammatory reaction to the dead cells. MORPHOLOGY Necrosis is characterized by changes in the cytoplasm and nuclei of the injured cells (Figs. 1-6, left, and 1-8, C). * Cytoplasmic changes. Necrotic cells show increased eosinophilia (i.e., pink staining from the eosin dye--the E in the hematoxylin and eosin stain), attributable in pa to increased binding of eosin to denatured cyto- plasmic proteins and in pa to loss of the basophilia that is normally impaed by the ribonucleic acid (RNA) in the cytoplasm (basophilia is the blue staining from the hema- toxylin dye--the H in "H&E"). Compared with ble cells, the cell may have a more glassy, homogeneous appear- ance, mostly because of the loss of glycogen paicles. Myelin figures are more prominent in necrotic cells than during reversible injury. When enzymes have digested cytoplasmic organelles, the cytoplasm becomes vacuo- lated and appears "moth-eaten." By electron microscopy, necrotic cells are characterized by discontinuities in plasma and organelle membranes, marked dilation of mitochon- dria with the appearance of large amorphous densities, disruption of lysosomes, and intracytoplasmic myelin figures. * Nuclear changes. Nuclear changes assume one of three patterns, all due to breakdown of DNA and chromatin. The basophilia of the chromatin may fade (karyolysis), presumably secondary to deoxyribonuclease (DNase) activity. A second pattern is pyknosis, characterized by nuclear shrinkage and increased basophilia; the DNA con- denses into a solid shrunken mass. In the third pattern, karyorrhexis, the pyknotic nucleus undergoes fragmen- tation. In 1 to 2 days, the nucleus in a dead cell may completely disappear. Electron microscopy reveals pro- found nuclear changes culminating in nuclear dissolution. * Fates of necrotic cells. Necrotic cells may persist for some time or may be digested by enzymes and disappear. Dead cells may be replaced by myelin figures, which are either phagocytosed by other cells or fuher degraded into fatty acids. These fatty acids bind calcium salts, which may result in the dead cells ultimately becoming calcified. Refer robbins 9/e p834
Accumulation of calcium in endoplasmic reticulum
Myelin figures
ATP depletion
Shifting of Ribosomes
General pathology