Chapter 4 Cell Injury, Aging, Death PDF

Chapter 4 Cell Injury, Aging, and Death Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 1 Reversible Cell Injury  Hydropic swelling: cellular swelling due to accumulation of water First manifestation of most forms of reversible cell injury Results from malfunc...

Chapter 4 Cell Injury, Aging, and Death Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 1 Reversible Cell Injury  Hydropic swelling: cellular swelling due to accumulation of water First manifestation of most forms of reversible cell injury Results from malfunction of sodium-potassium pump with accumulation of sodium ions within the cell Any injury that results in loss of energy (ATP) will also result in swelling Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 2 Reversible Cell Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 3 Reversible Cell Injury  Hydropic swelling: cellular swelling due to accumulation of water Characterized by large, pale cytoplasm; dilated endoplasmic reticulum; and swollen mitochondria Generalized swelling of cells in organs can lead to increase in size and weight, indicated by “megaly” Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 4 Reversible Cell Injury (Cont.) Intracellular Accumulations  Excess accumulations of substances in cells may lead to cellular injury due to toxicity, immune response, and/or taking up cellular space  Characterized by: Excessive amounts of normal intracellular substance Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 5 Reversible Cell Injury (Cont.) Intracellular Accumulations  Characterized by  Accumulation of abnormal substances secondary to faulty metabolism or synthesis Accumulation of pigments or particles that cell is unable to degrade Common site of accumulation is liver Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 6 Reversible Cell Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 7 Reversible Cell Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 8 Reversible Cell Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 9 Reversible Cell Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 10 Cellular Adaptation  Atrophy: cells shrink and reduce their differentiated functions in response to normal and injurious factors General causes Disuse Denervation Ischemia Nutrient starvation Interruption of endocrine signals Persistent cell injury Aging Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 11 Cellular Adaptation (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 12 Cellular Adaptation (Cont.)  Hypertrophy: increase in cell mass accompanied by an augmented functional capacity in response to physiologic and pathophysiologic demands Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 13 Cellular Adaptation (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 14 Cellular Adaptation (Cont.)  Hyperplasia: increase in functional capacity related to an increase in cell number due to mitotic division Usually in response to increased physiologic demands or hormonal stimulation Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 15 Cellular Adaptation (Cont.)  Metaplasia: replacement of one differentiated cell type with another Most often as an adaptation to persistent injury, with replacement of a cell type that is better suited to tolerate injurious stimulation Fully reversible when injurious stimulation is removed Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 16 Cellular Adaptation (Cont.)  Dysplasia: disorganized appearance of cells because of abnormal variations in size, shape, and arrangement Represents an adaptive effort gone astray Significant potential to transform into cancerous cells, thus referred to as preneoplastic lesions Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 17 Irreversible Cell Injury Necrosis  Usually occurs as a consequence of ischemia or toxic injury  Characterized by cell rupture, spilling of contents into extracellular fluid, and inflammation Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 18 Irreversible Cell Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 19 Irreversible Cell Injury (Cont.) Four Types of Tissue Necrosis  Coagulative (most common type): process that begins with ischemia and ends with degradation of plasma membrane  Liquefactive: occurs with dissolution of dead cells, liquification of lysosomal enzymes, and formation of abscess or cyst from dissolved dead tissue Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 20 Irreversible Cell Injury (Cont.) Four Types of Tissue Necrosis  Fat necrosis  Death of adipose tissue Usually the result of trauma or pancreatitis Appears as a chalky white area of tissue Caseous necrosis Characteristic of lung damage secondary to tuberculosis Resembles clumpy cheese Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 21 Irreversible Cell Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 22 Irreversible Cell Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 23 Irreversible Cell Injury (Cont.) Gangrene  Cellular death in a large area of tissue  Results from interruption of blood supply to a particular part of the body  Dry gangrene Form of coagulative necrosis characterized by blackened, dry, wrinkled tissue separated by a line of demarcation from healthy tissue Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 24 Irreversible Cell Injury (Cont.) Gangrene  Wet gangrene  Form of liquefactive necrosis Typically found in internal organs Gas gangrene Results from infection of necrotic tissue by anaerobic bacteria (Clostridium), which is characterized by formation of gas bubbles in damaged muscle tissue Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 25 Irreversible Cell Injury (Cont.) Apoptosis  Occurs in response to injury that does not directly kill the cell, but triggers intracellular cascades that activate a cellular suicide response  Not always a pathologic process  Does not cause inflammation Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 26 Irreversible Cell Injury (Cont.) Two Types of Environmental or Extrinsic Signals May Induce Apoptosis  Withdrawal of “survival” signals that normally suppress apoptotic pathways, such as observed with cancer cells  Extracellular signals, such as the Fas ligand, bind to the cell and trigger death cascade through activation of “death receptors” Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 27 Irreversible Cell Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 28 Irreversible Cell Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 29 Irreversible Cell Injury (Cont.)  Apoptosis can also be triggered by intrinsic pathways In response to severe cell damage, a protein (p53, which is normally low in the body) will increase in response to cellular DNA damage, triggering the cell’s own death Involves numerous intracellular signals and enzymes Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 30 Irreversible Cell Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 31 Etiology of Cellular Injury Ischemia and Hypoxic Injury  Tissue hypoxia is most often caused by ischemia  Ischemia is the most common cause of cell injury and injures cells faster than hypoxia alone  Combination of disruption of oxygen supply with accumulation of metabolic waste Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 32 Etiology of Cellular Injury (Cont.) Gangrene  Cellular events lead to lactic acidosis  Cellular proteins and enzymes become more dysfunctional Up to a point, ischemic injury is reversible, but cell death occurs when plasma, mitochondrial, and lysosomal membranes are critically damaged Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 33 Etiology of Cellular Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 34 Etiology of Cellular Injury (Cont.) Nutritional Injury  Adequate amounts of fats, carbohydrates, proteins, vitamins, and minerals are essential for normal cellular function  Certain cell types more susceptible to injury than others Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 35 Etiology of Cellular Injury (Cont.) Nutritional Injury Nutritional deficiencies may result from Poor intake Altered absorption Impaired distribution by circulatory system Inefficient cellular uptake Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 36 Etiology of Cellular Injury (Cont.) Nutritional Injury  Common causes of malnutrition Poverty Chronic alcoholism Acute and/or chronic illness Self-imposed dietary restrictions Malabsorption syndromes  Nutritional excesses primarily result from excessive intake Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 37 Etiology of Cellular Injury (Cont.) Infectious and Immunologic Injury  Bacteria and viruses can injure cells in a variety of ways depending on it’s virulence  Added injury may occur indirectly by triggering body’s immune response Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 38 Etiology of Cellular Injury (Cont.) Chemical Injury  Toxic chemicals or poisons can cause cellular injury both indirectly and by becoming metabolized into reactive chemicals by the body Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 39 Etiology of Cellular Injury (Cont.) Physical and Mechanical Injury  Factors Extremes in temperature Abrupt changes in atmospheric pressure Mechanical deformation Electricity Ionizing radiation Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 40 Etiology of Cellular Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 41 Etiology of Cellular Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 42 Etiology of Cellular Injury (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 43 Cellular Aging Cellular Basis of Aging  Cumulative result of progressive decline in proliferation and reparative capacity of cells combined with exposure to environmental factors that cause accumulation of cellular and molecular damage  Responsible mechanisms include DNA damage, reduced proliferation capacity of stem cells, and accumulation of metabolic damage Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 44 Cellular Aging (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 45 Cellular Aging (Cont.) Physiologic Changes of Aging  Age-related decrease in functional reserve  Inability to adapt to environmental demand Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 46 Somatic Death    Death of the entire organism No inflammation or immunologic response occurs prior to death General features include cessation of respirations and heartbeat Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 47 Somatic Death (Cont.)   Presence of stiffened muscles throughout body after death (rigor mortis) eventually leads to release of lytic enzymes in body tissues, postmortem autolysis Determination of “brain death” as proof of somatic death Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. 48