Altered Cellular and Tissue Biology Chapter 2 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2 Cellular Injury Mechanisms Hypoxic injury Hypoxic injury Ischemia Ischemia Anoxia Anoxia Cellular responses Cellular responses Decrease in ATP, causing failure of sodium-potassium pump and sodium-calcium exchange Decrease in ATP, causing failure of sodium-potassium pump and sodium-calcium exchange Cellular swelling Cellular swelling Reperfusion injury Reperfusion injury

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Cellular Injury Mechanisms Free radicals and reactive oxygen species Free radicals and reactive oxygen species Electrically uncharged atom or group of atoms having an unpaired electron Electrically uncharged atom or group of atoms having an unpaired electron Lipid peroxidation Lipid peroxidation Alteration of proteins Alteration of proteins Alteration of DNA Alteration of DNA Mechanisms for inactivation of free radicals Mechanisms for inactivation of free radicals

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Free Radical Injury The result of oxidative stress The result of oxidative stress An atom or group of atoms having an unpaired electron An atom or group of atoms having an unpaired electron Unstable molecule Unstable molecule To stabilize itself, it gives up an electron or steals one from long chains of phospholipids in cell membranes (lipid peroxidation) 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. 5 Oxidation vs. Reduction Oxidation Oxidation Losing an electron Losing an electron Reduction Reduction Gaining an electron Gaining an electron

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Cellular Injury Mechanisms Chemical injury Chemical injury Lead Lead Carbon monoxide Carbon monoxide Ethanol Ethanol Mercury Mercury Social or street drugs Social or street drugs

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Unintentional and Intentional Injuries Blunt force injuries Blunt force injuries Application of mechanical energy to the body resulting in the tearing, shearing, or crushing of tissues Application of mechanical energy to the body resulting in the tearing, shearing, or crushing of tissues Contusion vs. hematoma Contusion vs. hematoma Abrasion Abrasion Laceration Laceration Fractures Fractures

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Unintentional and Intentional Injuries Sharp force injuries Sharp force injuries Incised wounds Incised wounds Stab wounds Stab wounds Puncture wounds Puncture wounds Chopping wounds Chopping wounds

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Unintentional and Intentional Injuries Gunshot wounds Gunshot wounds Entrance wounds Entrance wounds Contact-range entrance wound Contact-range entrance wound Intermediate-range entrance wound Intermediate-range entrance wound Tattooing and stippling Tattooing and stippling Indeterminate-range entrance wound Indeterminate-range entrance wound Exit wounds Exit wounds Shored exit wound Shored exit wound

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Unintentional and Intentional Injuries Asphyxial injuries Asphyxial injuries Caused by a failure of cells to receive or use oxygen Caused by a failure of cells to receive or use oxygen Suffocation Suffocation Strangulation Strangulation Hanging, ligature, and manual strangulation Hanging, ligature, and manual strangulation Chemical asphyxiants Chemical asphyxiants Drowning Drowning

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Infectious Injury Pathogenicity of a microorganism Pathogenicity of a microorganism Virulence of a microorganism Virulence of a microorganism Disease-producing potential Disease-producing potential Invasion and destruction Invasion and destruction Toxin production Toxin production Production of hypersensitivity reactions Production of hypersensitivity reactions

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Immunologic and Inflammatory Injury Phagocytic cells Phagocytic cells Immune and inflammatory substances Immune and inflammatory substances Histamine, antibodies, lymphokines, complement, and enzymes Histamine, antibodies, lymphokines, complement, and enzymes Membrane alterations Membrane alterations

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Injurious Genetic Factors Nuclear alterations Nuclear alterations Alterations in the plasma membrane structure, shape, receptors, or transport mechanisms Alterations in the plasma membrane structure, shape, receptors, or transport mechanisms Examples Examples Sickle cell anemia and muscular dystrophy Sickle cell anemia and muscular dystrophy

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Injurious Nutritional Imbalances Essential nutrients are required for cells to function normally Essential nutrients are required for cells to function normally Deficient intake Deficient intake Excessive intake Excessive intake

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Temperature Extremes Hypothermic injury Hypothermic injury Slows cellular metabolic processes Slows cellular metabolic processes ROS production ROS production Hyperthermic injury Hyperthermic injury Heat cramps Heat cramps Heat exhaustion Heat exhaustion Heat stroke Heat stroke

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Atmospheric Pressure Changes Sudden increases or decreases in atmospheric pressure Sudden increases or decreases in atmospheric pressure Blast injury Blast injury Decompression sickness or caisson disease Decompression sickness or caisson disease The bends The bends

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Ionizing Radiation Any form of radiation capable of removing orbital electrons from atoms Any form of radiation capable of removing orbital electrons from atoms X-rays, gamma rays, alpha and beta particles X-rays, gamma rays, alpha and beta particles Mechanism of damage Mechanism of damage Effects of ionizing radiation Effects of ionizing radiation Somatic, genetic, fetal Somatic, genetic, fetal

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Cellular Injury Illumination injury Illumination injury Eyestrain, obscured vision, and cataract formation Eyestrain, obscured vision, and cataract formation Caused by light modulation Caused by light modulation Mechanical stresses Mechanical stresses Physical impact, irritation, overexertion Physical impact, irritation, overexertion Noise Noise Acoustic trauma and noise-induced hearing loss Acoustic trauma and noise-induced hearing loss

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Manifestations of Cellular Injury Cellular accumulations (infiltrations) Cellular accumulations (infiltrations) Water Water Lipids and carbohydrates Lipids and carbohydrates Glycogen Glycogen Proteins Proteins

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Manifestations of Cellular Injury Cellular accumulations (infiltrations) Cellular accumulations (infiltrations) Pigments Pigments Melanin, hemoproteins, bilirubin Melanin, hemoproteins, bilirubin Calcium Calcium Urate Urate

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Cellular Death Necrosis Necrosis Sum of cellular changes after local cell death and the process of cellular autodigestion (autolysis) Sum of cellular changes after local cell death and the process of cellular autodigestion (autolysis) Processes Processes Karyolysis Karyolysis Nuclear dissolution and chromatin lysis Nuclear dissolution and chromatin lysis Pyknosis Pyknosis Clumping of the nucleus Clumping of the nucleus Karyorrhexis Karyorrhexis Fragmentation of the nucleus Fragmentation of the nucleus

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Necrosis Coagulative necrosis Coagulative necrosis Kidneys, heart, and adrenal glands Kidneys, heart, and adrenal glands Protein denaturation Protein denaturation

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Necrosis Liquefactive necrosis Liquefactive necrosis Neurons and glial cells of the brain Neurons and glial cells of the brain Hydrolytic enzymes Hydrolytic enzymes

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Necrosis Caseous necrosis Caseous necrosis Tuberculous pulmonary infection Tuberculous pulmonary infection Combination of coagulative and liquefactive necrosis Combination of coagulative and liquefactive necrosis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Necrosis Fat necrosis Fat necrosis Breast, pancreas, and other abdominal organs Breast, pancreas, and other abdominal organs Action of lipases Action of lipases

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Necrosis Gangrenous necrosis Gangrenous necrosis Clinical term Clinical term Dry vs. wet gangrene Dry vs. wet gangrene Gas gangrene Gas gangrene

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Apoptosis Programmed cellular death Programmed cellular death Mechanisms Mechanisms Necrosis vs. apoptosis Necrosis vs. apoptosis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Aging and Altered Cellular and Tissue Biology Aging vs. disease Aging vs. disease Normal life span Normal life span

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 29 Theories of Aging Accumulation of injurious events Accumulation of injurious events Genetically controlled program Genetically controlled program Theories Theories Genetic and environmental lifestyle factors Genetic and environmental lifestyle factors Alterations of cellular control mechanisms Alterations of cellular control mechanisms Degenerative extracellular changes Degenerative extracellular changes

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Aging Cellular aging Cellular aging Tissue and systemic aging Tissue and systemic aging Frailty Frailty

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 31 Somatic Death Death of an entire person Death of an entire person Postmortem changes Postmortem changes Algor mortis Algor mortis Livor mortis Livor mortis Rigor mortis Rigor mortis Postmortem autolysis Postmortem autolysis