cellular injury pdf

8/12/2019 Cellular Injury PDF

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CELLULAR INJURY - 1

Dr Ekta Bhutada

Senior Lecturer


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Cellular injury occurs when a stress exceeds

the cells ability to adapt

Stresscellular adaptationreversible

injuryirreversible injurycell death


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Factors affecting the severity of injury :

Type, length & severity of stress Type of affected cell -

Neurons & cardiac muscle > skeletal muscle

Acute > chronic injury


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A 35 year old man meets with an accident &

suffers severe blood loss.

What would be the sequence of events at

cellular & subcellular levels?

What is the fate of injured cells?


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HYPOXIC ISCHEMIC INJURY

Very common clinical scenario

Hypoxia

lack of O2

CausesIschemia, anemia, severe blood loss

Ischemia Reduced blood flow Hence hypoxia + lack of other substrates;

more harmful than hypoxia


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Reversible injury

Hallmark sign cellular swelling

Mechanism

ATP depletion

disruption of Na-K pump intracellular Na & water

disruption of Ca pump

intracellular Ca activated anaerobic glycolysislactic acid accumulation

enzymatic activity & protein denaturation


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Normal kidney tubules Reversible injury

Cellular swelling


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Other reversible injury

Fatty change

Mechanism

Hypoxia,Metabolic & toxic injuriesfatty

change in organs involved with fat metabolism


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Ultrastructural changes


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Irreversible injury

Hallmark features

Plasma membrane damage ATP,Ca & direct

Mitochondrial damage injuries

Mechanism

Plasma membrane damagecytosolic enzymesleak in serumdiagnostic utility; further ATP

depletion


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Mitochondrial damageATP depletion &

activation of apoptosis

Massive Ca influxprogression to cell death

Final consequence of irreversible injuryCell

death either by necrosis or apoptosis


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Free radical Injury

Free radicals unstable due to single unpairedelectron

ExamplesReactive oxygen species(ROS),

Fe2+, nitric oxide(NO)

Mechanism :

Release energydamage cell membranes,

proteins & DNA


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Free radicals removed by

AntioxidantsVit A, C, E Ferritin, transferrin, lactoferrin

Enzymescatalase, superoxide dismutase,

glutathione peroxidase

Excess of ROS (oxidative stress)reperfusion

injury, cancer, neurodegenerative diseases


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The End


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CELLULAR INJURY - 2

Dr Ekta Bhutada

Senior Lecturer


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NECROSIS

Cell death due to lethal injury

Contents from irreversibly damaged cells leakout

Inflammation elicited in the surrounding

tissue


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IRREVERSIBLE INJURY


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Morphology

Increased eosinophiliadue to denaturation of

intracellular protein & enzymatic digestion of

cell

Nuclear changes in cell death:

Pyknosis

Karyolysis

Karyorrhexis


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Types of necrosis

Coagulative necrosis

Liquefactive necrosis

Caseous necrosis


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Architecture of the dead tissue is preserved

More eosinophilia & nucleus disappears

Mechanism: denaturation of proteins &

destruction of enzymes

Exampleischemic infarction of any solidorgan except brain


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Liquefactive necrosis

Necrotic tissue gets liquefied due to enzymatic

digestion of cells

Exampleischemic infarction of brain,

abscess


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Brain infarct


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Caseous necrosis

Characteristic of tuberculosis

C/o

caseous

i.e. cheese like friable area ofnecrosis


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Tuberculosis in lung & lymph node


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Caseous necrosis


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Other types

Gangrenous necrosis

Fat necrosis

Fibrinoid necrosis


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Gangrenous necrosis

Black dead tissue

Characteristic of ischemia of lower limb &

intestine

Dry gangrenecoagulative necrosis

Wet gangreneliquefactive necrosis due tosupervening infection


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Fat Necrosis

Focal areas of fat destruction

Characteristic ofpancreatitis

MechanismLipase activationfat

breakdownFA + Cachalky white

deposits (saponification)


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Fibrinoid necrosis

Necrotic damage to blood vessel wall &

deposition of fibrinlike material

Characteristic of vasculitisdeposition of

fibrinoid material in the blood vessel wall


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APOPTOSIS

Suicide program

Energy driven programmed cell death

Cells destined to dieactivate enzymes

break the cellapoptotic bodies

No inflammation


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Physiologic & Pathologic

Physiologicduring embryogenesis,

endometrial breakdown during menstrual

cycle

Pathologic(crucial in removing damaged cells

beyond repair) viral infections, degenerativediseases of CNS


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Mechanism

intrinsic (mitochondrial)

Initiation phase

extrinsic (death receptor)

Execution phase

Removal phase


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Di d f d l d


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Disorders of dysregulated

apoptosis

Defective apoptosiscancer, autoimmune

diseases

Increased apoptosisneurodegenerative

diseases


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FEATURES

CELL SIZE Enlarged Reduced

NUCLEUS Pyknosis/karyorrhexis/k

aryolysis

Fragmented

PLASMA MEMBRANE &

CELLULAR CONTENTS

Disrupted & contents

may leak out

Intact & no leakage

ADJACENT

INFLAMMATION

Frequent No

PHYSIOLOGIC/PATHOLO

GIC

Always pathologic Physiologic

/Pathologic

NECROSIS APOPTOSIS


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Autophagy

A process that triggers cell death which is

distinct from necrosis & apoptosis

Cell eat its own contents

Helps a cell to survive in various conditions

like nutrient deprivation

Exact mechanism not known


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The End

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