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Chapter 1 Cell Pathology Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Outline of Cell Pathology Structure & function of normal cell Integration & coordination of cell function; response to injury Reversible; Irreversible Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 2 Rudolf Virchow (1821–1902) Introduced concept of cellular pathology Considered father of modern cellular pathology 1821- 1902, Berlin, pathologist and statesman, one of the most prominent physicians of the 19th century. He pioneered the modern concept of pathological processes by his application of the cell theory to explain the effects of disease in the organs and tissues of the body. Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 3 Structure & Function of a Cell Basic unit of life Nucleus Cytoplasm Mitochondria Ribosome Endoplasmic reticulum Golgi apparatus Lysosome Cytoskeleton Plasma membrane Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 4 The Nucleus Essential component of most living cells Contains DNA, RNA, nuclear proteins Major components seen by electron microscope: Nuclear membrane Chromatin (during mitosis becomes chromosomes) Nucleolus Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 5 Gene Expression Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 6 Plasma Membrane Forms outer surface of cell Composed of proteins, lipids, carbohydrates Bilayer surface Internal External Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 7 Equilibrium of Cell Steady state maintained between cell & its surrounding Equilibrium = homeostasis External stimuli can alter homeostasis Imbalance in homeostasis can cause: Cell injury Cell death Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 8 Steady State (Homeostasis) Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 9 INTRODUCTION WHEN AN INJURY OCCURS IT MUST GO THROUGH 3 STAGES OF HEALING 10 Courtesy of Tracie Yarber Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Stage 1: Acute Inflammatory Increase blood flow to the area that brings cells and chemicals to begin the healing process. Phagocytes- Eat up dead cells. Leukocytes- Infection fighting white blood cells. Platelets-Carry blood clotting materials. THIS STAGE LASTS FOR ABOUT 2 DAYS Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 11 Courtesy of Tracie Yarber Stage 2: Repair The injured area has been filled with the blood, cells, and chemicals needed to rebuild the injury Fibroblasts begin building fibers across the injury and form the scar. THIS PROCESS LASTS FROM 6 WEEKS TO 3 MONTHS. Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 12 Courtesy of Tracie Yarber Stage 3: Remodeling Builds tissue strength in the tendons, ligaments and muscles to withstand stress applied to the body. THIS STAGE TAKES UP TO A YEAR OR MORE. Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 13 CONCLUSION Soft tissue healing requires the tissue to go through 3 stages: Acute Inflammatory Repair Remodeling The injury should be healed completely after about a years time. Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 14 Cell Injury Reversible cell injury Cellular swelling Irreversible cell injury Cell death Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 15 Reversible Cell Injury Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 16 Cellular Swelling Normal microvilli Swollen microvilli Invagination of cell membrane Swollen mitochondria, dilated RER Loss of intracellular contact Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 17 Cell Membrane Permeability Changes Regulates flow of sodium (Na) & potassium (K) across membrane Na+/K+ ATPase pump requires energy produced by mitochondria Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 18 Nuclear Changes in Irreversible Cell Injury Pyknosis: condensation Karyorrhexis: fragmentation Karyolysis: dissolution of nuclear structure as result of enzymatic digestion Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 19 Causes of Cell Injury Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply Anoxia means a total depletion in the level of oxygen, an extreme form of hypoxia or "low oxygen". Microbes Inflammation Immune reactions Genetic & metabolic disorders Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 20 Major Causes of Hypoxia/Anoxia Hydrogen peroxide link Superoxide, is a compound that contains the superoxide anion with the chemical formula O2−. Hydroxyl radical Free radical and aging. The human body is in constant battle to keep from aging. Research suggests that free radical damage to cells leads to the pathological changes associated with aging. Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 21 Reperfusion Injury During anoxia, radicals will build up. After a heart attack, if the blood flow is reestablished, then the spreading of these radicals will actually increase the cellular death. Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 22 Reperfusion Injury Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function. Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 23 Toxic Cell Injury Direct toxin: heavy metals (i.e., mercury) disrupt S-S bonds Indirect toxin: carbon tetrachloride metabolized in liver to form carbon trichloride, which is more toxic Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 24 Microbial Pathogens Bacteria: produce toxins Viruses: “kill cells from within” Direct Indirect Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 25 Viral Cell Injury Lytic cycle- Makes new viruses Lysogenic cycle – hides inside the DNA Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. 26