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Transcript
Cell Injury
Dr. Peter Anderson, UAB Pathology
Cell Injury
Atrophy
Hypertrophy
Hyperplasia
Metaplasia
Cell Injury
Copyright © 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved
Conclusion
Causes of Cellular Injury
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•
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•
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•
•
Oxygen Deprivation
Physical Agents
Chemical Agents and Drugs
Infectious Agents
Immunologic Reactions
Genetic Derangements
Nutritional Imbalances
Causes of Cellular Injury
Oxygen Deprivation
• Hypoxia
– Decreased availability of oxygen
• pneumonia
– Loss of oxygen carrying capacity of blood
• anemia
• Ischemia
– Insufficient blood supply
– Occlusion of artery or vein
Case Scenario
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
• You do a physical exam and draw blood
for cardiac work-up.
• The STAT blood work shows an elevated
CK-MB and troponin I.
• You send him for an emergency cardiac
catheterization and possible angioplasty
Coronary Arteriogram
Myocardial Infarction
Myocardial Infarction
Morphology of Injured Cells
• Reversible injury
– cell swelling leading to hydropic change or vacuolar
degeneration
• Irreversible injury
– cell death leading to necrosis
– nuclear pyknosis followed by karyorrhexis and
karyolysis
Reversible Injury
Hydropic Degeneration
Morphology of Injured Cells
• Reversible injury
– cell swelling leading to hydropic change or vacuolar
degeneration
• Irreversible injury
– necrosis
– nuclear pyknosis followed by karyorrhexis and
karyolysis
Cell Death
(necrosis)
Cell Death
Oxygen-Derived Free Radicals
• Free radicals - chemical species that have
a single unpaired electron in an outer
orbit: O2 ; H2O2; ·OH; ONOO
• Free radicals initiate autocatalytic
reactions - propagate chain of damage
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
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
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-)
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
EQUILIBRIUM
Fe2+
Vitamins A , C, E
Glutathione peroxidase
SOD, Catalase
Transferrin
ROS Production
ROS Removal
Pathologic Effects of ROS
• Lipid peroxidation in membranes.
• Oxidative modification of proteins.
• DNA damage
Cell Injury
Copyright © 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved
Conclusion
Necrosis & Apoptosis
Types of Necrosis
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•
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Coagulative necrosis
Liquefaction necrosis
Fat necrosis
Caseous necrosis
Fibrinoid necrosis
Gangrenous necrosis
Coagulative Necrosis
• Dissolution of nucleus with preservation
cellular shape and tissue architecture
• Coagulation (denaturation) of cell
proteins
Coagulative Necrosis
Coagulative Necrosis
Liquefaction Necrosis
• Hydrolytic enzymes cause autolysis and
heterolysis (liquefacation) of cells/tissues
• Examples:
– Brain infarct
– Abscess
Liquefaction Necrosis
Liquefaction Necrosis
Liquefaction Necrosis
Fat Necrosis
• Destruction of adipose tissue due to
the action of lipases
• Examples:
– Pancreatitis
– Pancreatic trauma
Pancreatic Fat Necrosis
Pancreatic Fat Necrosis
Pancreatic Fat Necrosis
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
Caseous Necrosis - TB
Caseous Necrosis - TB
Fibrinoid Necrosis
• Necrotic tissue due to immunologic
reaction
• Usually seen in blood vessels with
deposition of complement and antibodies
in vessel wall
Fibrinoid Necrosis
Gangrenous Necrosis
• Coagulative necrosis with 2o bacteria infection
leading to liquefaction
• Dry gangrene
– coagulative necrosis is the predominant pattern
• Wet gangrene
– liquefactive process is the dominant pattern
Gangrenous Necrosis
Apoptosis
Apoptosis
• Programmed cell death
Apoptosis
• Physiologic Apoptosis
– Embryogenesis
– Hormone-dependent involution
• menstrual cycle, lactating breast
• Pathologic Apoptosis
– Viral diseases leading to cell death
– Injurious agents
• anticancer drugs, radiation
Apoptosis - Mechanisms
• Activation of endonuclease
• Cytoskeleton disruption by proteases
• Cytoplasmic protein cross-linking by
transglutaminase
• Cell surface changes leading to
phagocytosis
Apoptosis
Morphologic Characteristics
•
•
•
•
•
General cell shrinkage
Chromatin condensation
Bleb formation & apoptotic bodies
Phagocytosis
Lack of an inflammatory reaction
Apoptosis
Apoptosis
Copyright © 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved
Apoptosis - Prostate
The End
Cell Injury, Necrosis,
& Apoptosis
The End
Cell Injury
Case Reviews:
Interactive Pathology Laboratory
Lab 1b Cellular Injury