1. Cell Injury
Dr. Peter Anderson, UAB Pathology

2. Cell Injury
Atrophy
Hypertrophy
Hyperplasia
Metaplasia

3. Cell Injury Conclusion
Copyright © by Saunders, an imprint of Elsevier Inc. All rights reserved

4. Causes of Cellular Injury
Oxygen Deprivation
Physical Agents
Chemical Agents and Drugs
Infectious Agents
Immunologic Reactions
Genetic Derangements
Nutritional Imbalances

5. 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

6. 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.

7. 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

8. Coronary Arteriogram

9. Myocardial Infarction9

10. Myocardial Infarction

12. 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

13. Reversible Injury

14. Hydropic Degeneration

15. 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

16. Cell Death
(necrosis)

17. Cell Death

18. 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

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

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

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-)

22. Removal of ROS Antioxidants Iron and copper binding proteins Enzymes
vitamins E, A, C and glutathione
Iron and copper binding proteins
transferrin, ferritin, lactoferrin, and ceruloplasmin
Enzymes
Catalase, Superoxide dismutases (SODs), Glutathione peroxidase

23. EQUILIBRIUM ROS Production ROS Removal
Fe2+
Vitamins A , C, E
Glutathione peroxidase
SOD, Catalase
Transferrin
ROS Production
ROS Removal

24. Pathologic Effects of ROS
Lipid peroxidation in membranes.
Oxidative modification of proteins.
DNA damage

25. Cell Injury Conclusion
Copyright © by Saunders, an imprint of Elsevier Inc. All rights reserved

26. Necrosis & Apoptosis

27. Types of Necrosis Coagulative necrosis Liquefaction necrosis
Fat necrosis
Caseous necrosis
Fibrinoid necrosis
Gangrenous necrosis

28. Coagulative Necrosis
Dissolution of nucleus with preservation cellular shape and tissue architecture
Coagulation (denaturation) of cell proteins

29. Coagulative Necrosis

30. Coagulative Necrosis

31. Liquefaction Necrosis
Hydrolytic enzymes cause autolysis and heterolysis (liquefacation) of cells/tissues
Examples:
Brain infarct
Abscess

32. Liquefaction Necrosis

33. Liquefaction Necrosis

34. Liquefaction Necrosis

35. Fat Necrosis
Destruction of adipose tissue due to the action of lipases
Examples:
Pancreatitis
Pancreatic trauma

36. Pancreatic Fat Necrosis

37. Pancreatic Fat Necrosis

38. Pancreatic Fat Necrosis

39. 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

40. Caseous Necrosis - TB

41. Caseous Necrosis - TB

42. Fibrinoid Necrosis Necrotic tissue due to immunologic reaction
Usually seen in blood vessels with deposition of complement and antibodies in vessel wall

43. Fibrinoid Necrosis

44. 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

45. Gangrenous Necrosis

46. Apoptosis

47. Apoptosis
Programmed cell death

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

49. Apoptosis - Mechanisms
Activation of endonuclease
Cytoskeleton disruption by proteases
Cytoplasmic protein cross-linking by transglutaminase
Cell surface changes leading to phagocytosis

50. Morphologic Characteristics
Apoptosis
Morphologic Characteristics
General cell shrinkage
Chromatin condensation
Bleb formation & apoptotic bodies
Phagocytosis
Lack of an inflammatory reaction

51. Apoptosis

52. Apoptosis
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53. Apoptosis - Prostate

55. Cell Injury, Necrosis, & Apoptosis
The End
Cell Injury, Necrosis, & Apoptosis

56. Interactive Pathology Laboratory
The End
Cell Injury
Case Reviews:
Interactive Pathology Laboratory
Lab 1b Cellular Injury