Cell Injury Conclusion Copyright 2010 by Saunders, an imprint
of Elsevier Inc. All rights reserved
Slide 4
Causes of Cellular Injury Oxygen Deprivation Physical Agents
Chemical Agents and Drugs Infectious Agents Immunologic Reactions
Genetic Derangements Nutritional Imbalances
Slide 5
Causes of Cellular Injury Hypoxia Decreased availability of
oxygen pneumonia Loss of oxygen carrying capacity of blood anemia
Oxygen Deprivation Ischemia Insufficient blood supply Occlusion of
artery or vein
Slide 6
A 65-year-old man comes to the emergency room because of
crushing sensation in his chest and pain radiating to his jaw. Case
Scenario
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You do a physical exam and draw blood for cardiac work-up. Case
Scenario The STAT blood work shows an elevated CK-MB and troponin
I. You send him for an emergency cardiac catheterization and
possible angioplasty
Slide 8
Coronary Arteriogram
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Myocardial Infarction
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Morphology of Injured Cells Reversible injury Reversible injury
cell swelling leading to hydropic change or vacuolar degeneration
Irreversible injury Irreversible injury cell death leading to
necrosis nuclear pyknosis followed by karyorrhexis and
karyolysis
Slide 13
Reversible Injury
Slide 14
Hydropic Degeneration
Slide 15
Morphology of Injured Cells Reversible injury Reversible injury
cell swelling leading to hydropic change or vacuolar degeneration
Irreversible injury Irreversible injury necrosis nuclear pyknosis
followed by karyorrhexis and karyolysis
Slide 16
Cell Death (necrosis)
Slide 17
Cell Death
Slide 18
Oxygen-Derived Free Radicals Free radicals - chemical species
that have a single unpaired electron in an outer orbit: O 2 ; H 2 O
2 ; OH; ONOO Free radicals initiate autocatalytic reactions -
propagate chain of damage
Slide 19
Oxygen-Derived Free Radicals Reactive oxygen species (ROS) are
a type of oxygen-derived free radical ROS are produced normally in
cells during mitochondrial respiration and energy generation ROS
kept in low steady state levels by cellular scavenger systems
Slide 20
Oxygen-Derived Free Radicals Oxidative Stress ROS production
(e.g., inflammation) or a reduction in scavenging systems leads to
an excess of free radicals: oxidative stress
Slide 21
Generation of ROS Oxidation - reduction reactions Absorption of
radiant energy Rapid bursts of ROS produced in activated leukocytes
during inflammation Enzymatic metabolism of exogenous chemicals or
drugs Transition metals - iron and copper Nitric oxide (NO) &
peroxynitrite anion (ONOO - )
Slide 22
Removal of ROS Antioxidants vitamins E, A, C and glutathione
Iron and copper binding proteins transferrin, ferritin,
lactoferrin, and ceruloplasmin Enzymes Catalase, Superoxide
dismutases (SODs), Glutathione peroxidase
Slide 23
ROS ProductionROS Removal Fe 2+ Vitamins A, C, E Glutathione
peroxidase SOD, Catalase Transferrin EQUILIBRIUM
Slide 24
Pathologic Effects of ROS Lipid peroxidation in membranes.
Oxidative modification of proteins. DNA damage
Slide 25
Cell Injury Conclusion Copyright 2010 by Saunders, an imprint
of Elsevier Inc. All rights reserved
Coagulative Necrosis Dissolution of nucleus with preservation
cellular shape and tissue architecture Coagulation (denaturation)
of cell proteins
Slide 29
Coagulative Necrosis
Slide 30
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Liquefaction Necrosis Hydrolytic enzymes cause autolysis and
heterolysis (liquefacation) of cells/tissues Examples: Brain
infarct Abscess
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Liquefaction Necrosis
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Fat Necrosis Destruction of adipose tissue due to the action of
lipases Examples: Pancreatitis Pancreatic trauma
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Pancreatic Fat Necrosis
Slide 37
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Caseous Necrosis Combination of coagulative and liquefaction
necrosis Primarily found in the center of tubercles Inability to
digest and remove material from center of granuloma
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Caseous Necrosis - TB
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Fibrinoid Necrosis Necrotic tissue due to immunologic reaction
Usually seen in blood vessels with deposition of complement and
antibodies in vessel wall
Slide 43
Fibrinoid Necrosis
Slide 44
Gangrenous Necrosis Coagulative necrosis with 2 o bacteria
infection leading to liquefaction Dry gangrene coagulative necrosis
is the predominant pattern Wet gangrene liquefactive process is the
dominant pattern
Slide 45
Gangrenous Necrosis
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Apoptosis
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Programmed cell death
Slide 48
Apoptosis Physiologic Apoptosis Embryogenesis Hormone-dependent
involution menstrual cycle, lactating breast Pathologic Apoptosis
Viral diseases leading to cell death Injurious agents anticancer
drugs, radiation
Slide 49
Apoptosis - Mechanisms Activation of endonuclease Cytoskeleton
disruption by proteases Cytoplasmic protein cross-linking by
transglutaminase Cell surface changes leading to phagocytosis
Slide 50
Apoptosis General cell shrinkage Chromatin condensation Bleb
formation & apoptotic bodies Phagocytosis Lack of an
inflammatory reaction Morphologic Characteristics
Slide 51
Apoptosis
Slide 52
Copyright 2010 by Saunders, an imprint of Elsevier Inc. All
rights reserved
Slide 53
Apoptosis - Prostate
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The End Cell Injury, Necrosis, & Apoptosis
Slide 56
The End Case Reviews: Interactive Pathology Laboratory Lab 1b
Cellular Injury Cell Injury