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