Cell Injury Types and Mechanisms PDF

L28 TYPES AND MECHANISMS OF CELL INJURY ILOs By the end of this lecture, students will be able to 1. Relate noxious physical, chemical, biological, genetic, and immunological agents to cellular changes. 2. Explore the pathogenesis of cell injury and its impact on...

L28 TYPES AND MECHANISMS OF CELL INJURY ILOs By the end of this lecture, students will be able to 1. Relate noxious physical, chemical, biological, genetic, and immunological agents to cellular changes. 2. Explore the pathogenesis of cell injury and its impact on disease development especially in a case of hypoxia, oxidative stress, toxins, DNA damage and other factors. Introduction: Normal cells are in a state of homeostasis (A healthy state that is maintained by the constant adjustment of biochemical and physiological pathways). Injury is defined as a set of biochemical and/or morphologic changes that occur when the state of homeostasis is disturbed by adverse influences. Cells react against various noxious endogenous or exogenous agents through different stages of progressive cellular impairment responses, including: Adaptation Reversible cell injury; Abnormal intracellular accumulation Irreversible cell injury; (cell death; necrosis, apoptosis and autophagy) So, we may consider adaptation, intracellular accumulation and cell death as stages of progressive cellular impairment following different types of insults. Causes of Cell Injury 1- Oxygen Deprivation: Hypoxia is a deficiency of oxygen, which causes cell injury by reducing aerobic oxidative respiration. Depending on the severity of the hypoxic state, cells may adapt, undergo injury, or die. Causes of hypoxia: It occurs due to inadequate oxygenation of the blood due to: 1  A. Ischemia; due to reduced arterial blood flow. B. Cardiorespiratory failure and inadequate oxygenation of blood. C. Reduced oxygen-carrying capacity of the blood; as in anemia or carbon monoxide poisoning. D. Severe blood loss. 2- Physical Agents: as mechanical trauma, extremes of temperature (burns and frostbite), sudden changes in atmospheric pressure, radiation or electric shock. 3- Chemical Agents and Drugs: Hypertonic chemicals, high oxygen concentrations, trace amounts of poisons, and environmental pollutants as insecticides, and herbicides; industrial and occupational hazards as well as cigarettes, alcohols and some drugs. 4- Infectious, biological, Agents: Range from sub microscopic viruses to tapeworms. 5- Immunologic Reactions: Immune reactions to many external or endogenous agents. 6- Genetic Abnormalities: leads to deficient protein function and accumulation of damaged DNA which trigger cell death by apoptosis when they are beyond repair. 7- Nutritional Imbalances: Deficiencies of protein, vitamins, obesity and high lipids diets. 8- Aging: Cellular aging or senescence leads to impaired ability of the cells to undergo replication and repair. Some principles of cell injury: The biochemical pathways in cell injury can be organized around a few general principles: The cellular response to injury depends on its nature, duration, and severity. The consequences of injury depend on the type, state, and adaptability of the injured cell. Any injurious stimulus may simultaneously trigger multiple interconnected mechanisms that damage cells. The consequences of injury of each of these cellular components are distinct but overlapping. All stresses and noxious influences exert their effects within minutes and hours at the molecular / biochemical and ultrastructural level, but it takes hours to days to appear at light microscopy and more to become visible by naked eye examination. Reversible injury: is a condition which is capable of being reversed with restoration of previous state of cells following the removal of the adverse influences. Irreversible injury: occurs where injurious stimulus is persistent or severe and cellular changes are not able to be undone or return back to normal status, and ultimately undergo cell death. Intracellular Targets of Injurious Stimuli: Cell injury results from disturbance in any of five essential cellular elements: 1- ATP production (mostly through effects on mitochondrial aerobic respiration) 2- Mitochondrial integrity independent of ATP production 3- Plasma membrane integrity, responsible for ionic and osmotic homeostasis 4- Protein synthesis, folding, degradation, and refolding 5- Integrity of the genetic apparatus General Mechanisms of Cell Injury; 1- Depletion of Adenosine Triphosphate 2  ATP is required for membrane transport, protein synthesis, lipogenesis, and the deacylation- reacylation reactions necessary for phospholipid turnover. Decreased ATP synthesis and ATP depletion are common consequences of both ischemic, chemical \toxic injury and mitochondrial damage. Depletion of ATP to