Cell Injury and the Pathogenesis of Human Disease (PATH 6226)

1. Cell Injury and the Pathogenesis of Human Disease(PATH 6226) May 2 and 4, 2011 Paul Boor M.D. “Cellular basis of disease” 200 years of observation: organ and microscopic

2. SUGGESTED READING(PATHOLOGIC BASIS OF DISEASE, 8th EDITION) CHAPTER 1Cellular Response to Stress and Toxic Insult; Adaptation, Injury, Death (pp 3-42) CHAPTER 3Tissue Renewal, Repair, and Regeneration (pp 79-110)

3. Rudolph Virchow (1821-1902)Cell Theory“Social Medicine”

4. Cell Injury – General Considerations • Numerous causes • Biochemical events precede structural • Duration and intensity of exposure important (direct dose/response relationship) • Injury may be TISSUE (or cell) specific • Injury depends of ability of cells to respond, resist, and repair injury

5. Cell Injury – Causes • Hypoxia / Ischemia • Physical (mechanical, heat, radiation) • Chemical • Biologic Agents • Immunologic (host) reaction • Genetic derangement • Nutritional imbalance, deficiency

19. Cellular Degeneration Sublethal, usually reversible forms of cellular injury unassociated with severe cellular dysfunction.

22. Oxidative Stress and Cell Injury

33. Necrosis (or “Oncosis”) VSApoptosis

37. Types of Necrosis • Coagulation • Liquefactive • Caseous • “Fat” necrosis

40. Liquefactive Necrosis

42. Caseous Necrosis

45. “Fat” Necrosis

47. Key Words(Week 1 BBSC 6626) • Anatomy of the hepatic lobule; • Cell: Hepatocyte, Kupffer cell, bile ductules; • Acetaminophen; • Cytochrome p450s; imines; • Reactive oxygen species; reactive nitrogen species; peroxynitrite; • Adducts

50. Hepatic Injury: Regenerative Nodules