1-mcp1-intro.2006 - same for 07 - columbia university
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Introduction to Cell Injury1. A brief illustrated hx of pathology2. Basic principles of cell injury:
-agents of injury-cellular/tissue adaptive responses-prototypes of cell injury-cell death: NECROSIS
Pathology• The study of disease
-Anatomic: surgical/autopsy/subspecialty (renal/liver)
-Clinical: laboratory tests--blood bank--tx med.--microbiology
• What do we do?Diagnosis—teaching--research
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Giovanni BatistaMorgagni:
1760: “The Seatsand Causes ofDisease”
John Hunter:
•Gross organmuseum
(Royal Collegeof Surgeons, UK)
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Marie Francois Bichat:
•Tissues are composedof organs
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Rokitansky:
•Performed 30,000 autopsies
•Observed 60,000autopsies
•En bloc dissection
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Virchow: All disease begins in the cell (Cellularpathologie)
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Cesar Milstein
Nobel Prize 1984Monoclonal Ab’s
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Gene chip microarray analysis: 2000-each column represents the data from amicroarray hybridized with a complementaryRNA pool (Red = high expression; Green = low expression)
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Agents of Injury
•Genetic•Nutritional•Physical•Immune•Infectious•Chemicalcell
Genetic
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Nutritional
Excess:-lipid-carbohydrate-vitamin
Deficiency:-vitamin-protein-calorie
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O2OH
H2O2
free radicals
Physical
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Chemical
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ImmuneImmune: Autoimmune hepatitis: Autoimmune hepatitisAttack against host Attack against host hepatocyteshepatocytes by lymphocytesby lymphocytes
Infectious
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***Stem cells: b.m.-derived / local organ
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Cellular Physiologic Adaptations To Injury
normal
Prototypes of cell injury
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• H2O2
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Reversible Irreversible
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NecrosisExample: coagulative necrosis due to
ischemia/hypoxia• Increased eosinophilia –eosin binds denat.prot.• Cell swollen—membrane permeability altered• Cytoplasm glassy—loss of glycogen• Cytoplasm vacuolated—enzymatic degradation of
organelles• Nuclear pyknosis-karyorrhexis-karyolysis—
enzymatic denaturation/degeneration of nucleoprotein
• Necrosis elicits inflammation!!! (vs. apoptosis)
Nuclear changes in necrosis
…Necrosis
pyknosis karyorrhexis karyolysisViable cell
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