NSG 530 CH. 4 ALTERED CELL & TISSUE EXAM QUESTIONS AND ANSWERS WITH COMPLETE SOLUTIONS VERIFIED LATEST UPDATE

NSG 530 CH. 4 ALTERED CELL & TISSUE EXAM QUESTIONS AND ANSWERS WITH COMPLETE SOLUTIONS VERIFIED LATEST UPDATE When does a cell become irreversibly injured? 1. The exact point of irreversible injury can vary based on a variety of factors, and the exact point of irreversible damage is up for debate. However, structurally, when severe vacuolization of the mitochondria occurs and calcium moves into the cell, irreversible injury is imminent. Discuss the pathogenesis of hypoxic injury. Hypoxia leads to a reduction in ATP levels which causes the plasma membrane's sodium-potassium (Na+-K+) pump and sodium-calcium exchange mechanism to fail, leading to an intracellular accumulation of sodium and calcium and diffusion of potassium out of the cell. Sodium and water then can enter the cell freely. The entire cell becomes markedly swollen, with increased concentrations of sodium, water, and chloride and decreased concentrations of potassium. Continued hypoxic injury with accumulation of calcium subsequently activates multiple enzyme systems resulting in membrane damage, cytoskeleton disruption, DNA and chromatin degradation, ATP depletion, and eventual cell death. What are the mechanisms of ischemia- reperfusion injury? 1. Restoration of blood flow and oxygen to ischemic tissues can increase recovery of cells reversibly injured, but paradoxically result in additional injury known as ischemia-reperfusion injury. Mechanisms of ischemia-reperfusion injury include: a. Oxidative Stress: Reoxygenation induces oxidative stress by generating highly ROS and nitrogen species. These include hydroxyl radical (OH-), superoxide radical (O.2) and hydrogen peroxide (H202). Nitrogen based free radicals present mostly in the form of nitric oxide (NO) and are generated by endothelial cells, macrophages, neurons and other cells. The radicals further damage the already compromised membrane and facilitate calcium overload within the mitochondria. Additionally, reperfusion injury promotes pro-inflammatory neutrophil adhesion to the endothelium where they release toxic oxidants and harmful proteases. Antioxidants such as Vitamin C & E reverse neutrophil adhesion and neutrophol- mediated reperfusion in cardiac muscle. b. Increased intracellular calcium concentration - Intracellular and mitochondrial calcium accumulate within the cell during acute ischemia. Reperfusion results in more calcium influx because of damaged cell membranes and ROS-mediated injury to the sarcoplasmic reticulum. The increased calcium enhances mitochondrial permeability; damaged mitochondria have decreased or ceased production of ATP. c. Inflammation: Ischemic injury promotes inflammation. Dead cells stimulate immune cells to release cytokine-mediated danger signals, thus initiating inflammatory response. d. Complement activation: May exacerbate damage which has occurred secondary to reperfusion injury.