Chapter 2 Altered Cellular and Tissue Biology Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. Cellular Injury Mechanisms Hypoxic injury Ischemia Anoxia Cellular responses • Decrease in ATP, causing failure of sodium-potassium pump and sodium-calcium exchange • Cellular swelling Reperfusion injury Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 2 Cellular Injury Mechanisms Free radicals and reactive oxygen species Electrically uncharged atom or group of atoms having an unpaired electron Lipid peroxidation Alteration of proteins Alteration of DNA Mechanisms for inactivation of free radicals Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Free Radical Injury The result of oxidative stress An atom or group of atoms having an unpaired electron Unstable molecule To stabilize itself, it gives up an electron or steals one from long chains of phospholipids in cell membranes (lipid peroxidation) Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Oxidation vs. Reduction Oxidation Losing an electron Reduction Gaining an electron Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Cellular Injury Mechanisms Chemical injury Lead Carbon monoxide Ethanol Mercury Social or street drugs Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Unintentional and Intentional Injuries Blunt force injuries Application of mechanical energy to the body resulting in the tearing, shearing, or crushing of tissues Contusion vs. hematoma Abrasion Laceration Fractures Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Unintentional and Intentional Injuries Sharp force injuries Incised wounds Stab wounds Puncture wounds Chopping wounds Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Unintentional and Intentional Injuries Gunshot wounds Entrance wounds • Contact-range entrance wound • Intermediate-range entrance wound Tattooing and stippling • Indeterminate-range entrance wound Exit wounds • Shored exit wound Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Unintentional and Intentional Injuries Asphyxial injuries Caused by a failure of cells to receive or use oxygen Suffocation Strangulation • Hanging, ligature, and manual strangulation Chemical asphyxiants Drowning Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Infectious Injury Pathogenicity of a microorganism Virulence of a microorganism Disease-producing potential Invasion and destruction Toxin production Production of hypersensitivity reactions Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Immunologic and Inflammatory Injury Phagocytic cells Immune and inflammatory substances Histamine, antibodies, lymphokines, complement, and enzymes Membrane alterations Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Injurious Genetic Factors Nuclear alterations Alterations in the plasma membrane structure, shape, receptors, or transport mechanisms Examples Sickle cell anemia and muscular dystrophy Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Injurious Nutritional Imbalances Essential nutrients are required for cells to function normally Deficient intake Excessive intake Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Temperature Extremes Hypothermic injury Slows cellular metabolic processes ROS production Hyperthermic injury Heat cramps Heat exhaustion Heat stroke Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Atmospheric Pressure Changes Sudden increases or decreases in atmospheric pressure Blast injury Decompression sickness or caisson disease • “The bends” Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Ionizing Radiation Any form of radiation capable of removing orbital electrons from atoms X-rays, gamma rays, alpha and beta particles Mechanism of damage Effects of ionizing radiation Somatic, genetic, fetal Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Cellular Injury Illumination injury Eyestrain, obscured vision, and cataract formation Caused by light modulation Mechanical stresses Physical impact, irritation, overexertion Noise Acoustic trauma and noise-induced hearing loss Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Manifestations of Cellular Injury Cellular accumulations (infiltrations) Water Lipids and carbohydrates Glycogen Proteins Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Manifestations of Cellular Injury Cellular accumulations (infiltrations) Pigments • Melanin, hemoproteins, bilirubin Calcium Urate Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Cellular Death Necrosis Sum of cellular changes after local cell death and the process of cellular autodigestion (autolysis) Processes Karyolysis • Nuclear dissolution and chromatin lysis Pyknosis • Clumping of the nucleus Karyorrhexis • Fragmentation of the nucleus Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Necrosis Coagulative necrosis Kidneys, heart, and adrenal glands Protein denaturation Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Necrosis Liquefactive necrosis Neurons and glial cells of the brain Hydrolytic enzymes Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Necrosis Caseous necrosis Tuberculous pulmonary infection Combination of coagulative and liquefactive necrosis Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Necrosis Fat necrosis Breast, pancreas, and other abdominal organs Action of lipases Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Necrosis Gangrenous necrosis Clinical term Dry vs. wet gangrene Gas gangrene Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Apoptosis Programmed cellular death Mechanisms Necrosis vs. apoptosis Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Aging and Altered Cellular and Tissue Biology Aging vs. disease Normal life span Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Theories of Aging Accumulation of injurious events Genetically controlled program Theories Genetic and environmental lifestyle factors Alterations of cellular control mechanisms Degenerative extracellular changes Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 29 Aging Cellular aging Tissue and systemic aging Frailty Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Somatic Death Death of an entire person Postmortem changes Algor mortis Livor mortis Rigor mortis Postmortem autolysis Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 31