MECHANISMS OF CELL INJURY

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MECHANISMS OF CELL INJURY :

BY AYSHA SHAHNAWAZ MBBS (D.U.H.S) MECHANISMS OF CELL INJURY

CELL INJURY RESULTS FROM DIFFERENT CHEMICAL MECHANISMS THAT ACT ON SEVERAL CELLULAR COMPONENTS…AMONG THESE ARE::

Depletion of ATP Mitochondrial Damage Influx of Calcium and Loss of Calcium Homeostasis Accumulation of Oxygen-Derived free radicals ( Oxidative stress ) Defects in Membrane Permeability CELL INJURY RESULTS FROM DIFFERENT CHEMICAL MECHANISMS THAT ACT ON SEVERAL CELLULAR COMPONENTS…AMONG THESE ARE:

ATP DEPLETION::

THE MAJOR CAUSES OF ATP DEPLETION ARE: 1)ISCHEMIA(reduced blood supply and hence oxygen and nutrients) 2)CERTAIN TOXINS( e.g cyanides) THE MAJOR CAUSES OF ATP DEPLETION ARE 1)ISCHEMIA 2)MITOCHONDRI-AL DAMAGE 3)CERTAIN TOXINS AS CYANIDE ATP DEPLETION :

MITOCHON-DRI AL DAMAGE:

IN CASE OF MITOCHONDRIAL DAMAGE FORMATION OF “MITOCHONDRIAL PERMEABILITY TRANSITIONAL PORES” OCCUR THAT LEADS TO LOSS OF MEMBRANE POTENTIAL,FAILURE OF OXIDATIVE PHOSPHORILATION,PROGRESSIVE ATP DEPLETION AND FINALLY NECROSIS. MITOCHON-DRI AL DAMAGE

Slide 5:

“CYCLOPHILN D ” IS A PROTEIN FOUND IN STRUCTURE OF MITOCHONDRIAL PERMEABILITY TRANSITIONAL PORES. THE DRUG CYCLOSPORIN REDUCES CELL INJURY BY TARGETING CYCLOPHILIN D i.e prevents opening of these pores.

CALCIUM INFLUX AND LOSS OF CALCIUM HOMEOSTASIS:

ISCHEMIA AND CERTAIN TOXINS CAUSES AN INCREASE IN CYTOSOLIC CALCIUM CONCENTRATION INTIALLY BY RELEASING CALCIUM FROM INTRACELLULAR STORES AND LATER FROM INCREASED CALCIUM INFLUX ACROSS THE CELL MEMBRANE. INCREASED CYTOSOLIC CALCIUM CAUSES CELL INJURY BY SEVERAL MECHANISMS/ CALCIUM INFLUX AND LOSS OF CALCIUM HOMEOSTASIS

DEFECTS IN MEMBRANE PERMEABILITY;:

SEVERAL BIOCHEMICAL MECHANISMS CONTRIBUTE TO MEMBRANE DAMAGE THESE INVOLVE: 1)ATP DEPLETION 2)ROS 3)DECREASE PHOSPHOLIPID SYNTHESIS 4)INCREASED PHOSPHOLIPASE ACTIVITY 5)CYTOSKELETAL ABNORMALITIES CAUSED BY ACTIVATION OF PROTEASE AS A RESULT OF INCREASE CYTOSOLIC CALCIUM….. DEFECTS IN MEMBRANE PERMEABILITY;

OXIDATIVE STESS:

OXIDATIVE STESS

THANK YOU:

THANK YOU

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