Overview Introduction Cells constantly interact with their environment and try to maintain homeostasis cells respond to stress (e.g., physiologic and toxic) via adaptation to maintain viability and function cell injury results when the cell can no longer adapt to the stress, which can be reversible implies that once the stress is removed the cell can return to its original state irreversible when the stressful stimuli is excessive or persistent the cellular damage becomes irreversible and cells undergo cell death General mechanism of cell injury ATP depletion leads to reduced Na+/K+ ATPase activity causing cellular and endoplasmic reticulum swelling ↑ anaerobic glycolysis which subsequently leads to glycogen depletion ↑ lactic acid reduced calcium pump activity which alters calcium homeostasis and activates proteins reduced protein synthesis mitochondrial damage can result from hypoxia, reactive oxygen species (ROS), and ↑ intracellular calcium levels and leads to increased mitochondrial permeability which causes impaired oxidative phosphorylation resulting in the production of ROS (damages lipids, proteins, and nucleic acid) leakage of apoptotic proteins (e.g., cytochrome C and caspases) into the cellular cytoplasm DNA damage that is irreparable results in apoptosis apoptosis can also result in misfolded proteins Etiologies of cell injury includes hypoxia hypothermia can mitigate hypoxic injury by decreasing cellular metabolism and slowing reperfusion ischemia toxin-induced (e.g., ethanol and cigarette smoking) infectious agents genetic abnormalities aging imbalances in nutrition physical causes (e.g., trauma) Findings in Reversible and Irreversible Cellular Injury Reversible Irreversible Morphological findings cellular swelling nuclear chromatin clumping ribosomal detachments econdary to decreased protein synthesis membrane blebbing fatty change Morphological findings plasma membrane damage lysosomal rupture autolysis ↑mitochondrial permeability changes of the nucleus include pyknosis karyorrhexis karyolysis