Toxic Pathways Less Traveled
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Transcript Toxic Pathways Less Traveled
Cell Injury and the Pathogenesis
of Human Disease
(PATH 6226)
“Cellular basis of disease”
200 years of observation: organ and
microscopic
May 2 and 4, 2011
Paul Boor M.D.
SUGGESTED READING
(PATHOLOGIC BASIS OF DISEASE, 8th EDITION)
CHAPTER 1
Cellular Response to Stress and Toxic Insult;
Adaptation, Injury, Death (pp 3-42)
CHAPTER 3
Tissue Renewal, Repair, and Regeneration (pp 79-110)
Rudolph Virchow
(1821-1902)
Cell Theory
“Social Medicine”
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
Cell Injury – Causes
Hypoxia / Ischemia
Physical (mechanical, heat, radiation)
Chemical
Biologic Agents
Immunologic (host) reaction
Genetic derangement
Nutritional imbalance, deficiency
Cellular Degeneration
Sublethal, usually reversible forms of
cellular injury unassociated with severe
cellular dysfunction.
Oxidative Stress and Cell Injury
Necrosis (or “Oncosis”)
VS
Apoptosis
Types of Necrosis
Coagulation
Liquefactive
Caseous
“Fat” necrosis
Liquefactive Necrosis
Caseous Necrosis
“Fat” Necrosis
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
Hepatic Injury: Regenerative Nodules