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Date post: | 19-Jul-2015 |
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Health & Medicine |
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Reversible V/S Irreversible injury
Free Radical Injury
Cell Adaptations
Necrosis
Apoptosis
Intracellular accumulations
Cell Ageing
Cellular Injury & Adaptation:
Normal cell is in a dynamic state of “Homeostasis”
Normal physiologic stress : Normal homeostasis
Stress - Adaptation, e.g. hypertrophy, atrophy
Stress - Cell Injury
Reversible Irreversible Cell Death
Oxygen– deprivation: Hypoxia
Blood –deprivation : Ischemia
Physical—agents : Trauma, RTA
Chemical—agents : All drugs are poisons !
Infectious—agents : Bacterial, Viral, Fungal
Immunological—reactions : Autoimmune rn
Genetic-Rearrangements
Nutritional—imbalance: PEM, Malnutrition
1. Cell membrane integrity
2. Aerobic respiration
3. Protein synthesis
4. Genetic apparatus
Depending on : TypeDuration of Injury SeverityAdaptability
Injury at one locus leads to wide ranging
secondary effects
General Considerations:
Morphology becomes apparent late in cell injury.
Reaction of cell to injury depends on type of injury,
duration and severity.
Reaction of cell to injury also depends on the type, state
& adaptability of the cell.
Ultra-structural Changes
Light Microscopy Changes
Gross Morphological Change
Reduced oxidative phosphorylation & ATP depletion,
Cellular swelling & blebbing of plasma membrane
o Due to changes in ion concentrations and water influx,
Swelling of ER & Mitochondria,
Clumping of chromatin.
Point of No return: Lethal Hit– structural changes:
Amorphous densities in mitochondria: Myelin figure formation.
Loss of membrane permeability.
Swelling of mitochondria
Lysosome rupture
Nuclear condensation
Final result- cell adaptation /death.
Injurious Stimuli
Reversible stage
Apoptosis Necrosis
Reversible
Cell Injury
GENERAL BIOCHEMICAL MECHANISMS
Some pathogenic mechanisms are well defined for cell injury.
Ex: Cyanide inactivates the Cytochrome oxidase in
mitochondria
Bacteria elaborates phospholipases degrade cell
phospholipids
Many stimuli do not have precise mechanisms of cell injury..
Complex mechanisms involved.
ATP depletion
Oxygen deprivation and release of Reactive Oxygen
Species (ROS)
Loss of calcium Homeostasis
Defects in plasma membrane permeability
Mitochondrial damage
GENERAL BIOCHEMICAL MECHANISMS …Contd….
Ca++ : most imp. Mediator of cell injury.
Normal Levels of Calcium:
o Intracellular Ca++ < 0.1 mmol,
o Extracellular Ca++ 1.3 mmol.
Intracellular Ca++ is sequestered in Mitochondria & ER.
Increased cytosolic Ca++ activates various enzymes:
1. ATPases,
2. Phospholipases,
3. Proteases,
4. Endonucleases.
A CTIVATES
K+ Efflux Cellular Swelling
1st Reduced oxidative phosphorylation in
Mitochondria
2nd Depletion of ATP
3rd Reduced activity of Na pump
4th Increased glycolysis—decreased Ph
5th Detachment of ribosomes, reduced protein
synthesis, lipid deposition
6th Cellular swelling, Increased K efflux
Reversible injury– flow restored– may recover
Golden Period of ischemia
o Can save many lives
o Concept of emergency angiography in cath lab
Rarely the restoration may adversely damage the tissue This is Reperfusion Injury
Restored blood brings in high concentration of calcium
Increased local recruitment of inflammatory cells
Damaged mitochondria Increased ROS
INJURIOUS STIMULUS
Decreased ATP
LOSS OF ENERGY DEPENDENT CELULAR FUNCTIONS
MEMBRANE DAMAGE
MITOCHONDRIA DAMAGE
LYSOSOME RUPTURE
PLASMA MEMBRANE RUPTURE
INCREASED intracellular Ca++
REACTIVE OXYGEN SPECIES
PROTEIN BREAK DOWN DNA
DAMAGE
ENZYMATIC DIGESTION OF CELL COMPONENTS
LOSS OF CELL
CONTENTS
CELL DEATH