mcp1-intro.2006 - same for 07 - columbia

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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

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

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

Nutritional

Excess:-lipid-carbohydrate-vitamin

Deficiency:-vitamin-protein-calorie

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O2OH

H2O2

free radicals

Physical

Chemical

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ImmuneImmune: Autoimmune hepatitis: Autoimmune hepatitisAttack against host Attack against host hepatocyteshepatocytes by lymphocytesby lymphocytes

Infectious

***Stem cells: b.m.-derived / local organ

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Cellular Physiologic Adaptations To Injury

normal

Prototypes of cell injury

• H2O2

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Reversible Irreversible

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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