Cell Injury, Adaptation & Death Dr. Nabila Hamdi MD, PhD
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Cell Injury, Adaptation & Death
Dr. Nabila Hamdi
MD, PhD
Course Structure
Assessment
Methods Weight
Quizzes (best 2 out of 3) 20%
Assignments 5%
Mid-term exam 30%
Final exam 45%
The midterm and final exams are computer based - case oriented
problems
6th semester
Dr. Ahmed Ihab PL1
Dr. Hend EL Tayebi PL2
Dr. Nabila Hamdi PL3
Pathology & Histology PHTX 621
Cell Injury Inflammation Tissue Healing & Repair Immune Disorders Neoplasia
Course content
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How to study?
Lectures
Tutorials
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evelivesey.deviantart.com
Basic Science Cell, molecule
Clinical Practice Symptoms
Etiology
Pathogenesis
Pathology is the study of suffering
pathos logos
Why Pathology?
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ILOs
• Describe the major mechanisms whereby most injurious agents exert their effects
• Understand the examples of cell injury stated in this lecture
• Describe cell changes that occur with atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia, and state general conditions under which these changes occur
• State and discuss patterns of reversible/irreversible cell injury
• Differentiate cell death associated with apoptosis and necrosis
• Compare the pathogenesis of dystrophic and metastatic calcifications
• Define intracellular accumulations and cite examples
• Understand the process of aging 6
Outline I. Causes of Cell Injury
II. Mechanisms of Cell Injury 1. General Biochemical Mechanisms
2. Ischemic & Hypoxic Injury
3. Ischemia/Reperfusion Injury
4. Free Radical-Induced Cell Injury
5. Chemical Injury
III. Cellular Adaptation to Injury 1. Atrophy
2. Hypertrophy
3. Hyperplasia
4. Metaplasia
5. Subcellular Responses to Injury
6. Intracellular Accumulations
7. Pathologic Calcification
III. Reversible/Irreversible Injury
IV. Apoptosis/Necrosis
V. Ageing
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http://ww2.odu.edu/~czemlin/heartattacks.html
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Causes of Cell Injury
Cell Injury
Oxygen Deprivation Hypoxia: low O2 cc Ischemia: reduced blood supply
Chemical Agents poisons, air pollutants, insecticides, CO, ethanol, therapeutic drugs…
Infectious Agents
Immunologic Reactions autoimmune reactions, allergic reactions…
Genetic Defects Hb S Sickle cell anemia Enzyme metabolic diseases
Nutritional Imbalances Protein-calorie insufficiency Vitamin deficiencies Obesity, animal fat…
Physical Agents Trauma, radiation, electric shock, extremes of temperatures…
Aging Cellular senescence
Viruses, rickettsiae, bacteria, fungi, protozoans and worms
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Mechanisms of Cell Injury General Biochemical Mechanisms
Cell injury results from functional and biochemical abnormalities in one or more of several essential cellular components. The most important targets of injurious stimuli are (1) mitochondria, the sites of ATP generation; (2) cell membranes, on which the ionic and osmotic homeostasis of the cell and its organelles depends; (3) protein synthesis;
(4) the cytoskeleton; and (5) the genetic apparatus of the cell.
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Mechanisms of Cell Injury ATP Depletion
Depletion of ATP to less than 5% to 10% of normal levels has widespread effects on many critical cellular systems 12
Mechanisms of Cell Injury Oxygen in Cell Injury
The critical role of oxygen in cell injury Ischemia causes cell injury by reducing cellular oxygen supplies,
whereas other stimuli, such as radiation, induce damage by toxic activated oxygen species
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Mechanisms of Cell Injury Mitochondrial Damage
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Mechanisms of Cell Injury Calcium Influx
ATP-dependent calcium transporters (Ischemia/Toxins)
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Mechanisms of Cell Injury Defects in Membrane Permeability
The most important sites of membrane damage during cell injury are the mitochondrial membrane, the plasma membrane, and membranes of lysosomes. 16
Ischemic and Hypoxic Injury
Ischemia is the most common cause of cell injury in clinical medicine
Ischemia injures tissues faster than does hypoxia !
Why?
Anaerobic glycolysis (less efficient)
Anaerobic glycolysis No delivery of substrates
If oxygen is restored, all of these disturbances are reversible. If ischemia persists, irreversible injury and necrosis ensue.
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Free Radical-Induced Injury
The Stance of Antioxidants in Brain Tumors By Pinar Atukeren and M. Ramazan Yigitoglu
Sources of reactive oxygen species in the human body
Antioxidant defense mechanisms (II): enzymatic mechanisms José A. Hernández Cortés. Research Scientist (CEBAS-CSIC)
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Free Radical-Induced Injury
Cu2+/Fe2+
Endogenous or exogenous antioxidants (e.g., vitamins E, A, and C, and β-carotene)
Cell Injury. David S. Strayer Emanuel Rubin Copyright ©2009 Lippincott Williams & Wilkins
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Ischemia/Reperfusion Injury
Oxygen paradox
ROS generation
Inflammation
Calcium Influx
Medicine, Mediators of Lethal Reperfusion Injury: the Oxygen Paradox, by Ernst
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Chemical Injury
Some chemicals act directly • Mercuric chloride poisoning • Antineoplastic chemotherapeutic agents
Other chemicals must be first converted to reactive toxic metabolites • Carbon tetrachloride CCl4 CCl3
• Liver toxicity "fatty liver“ within 2 hours!
• Acetaminophen overdose Acute liver failure
Direct binding to critical molecular component or cellular organelle
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