2. cell injury etiology- mdzah- sp sinhasan

2.  Reversible V/S Irreversible injury
 Free Radical Injury
 Cell Adaptations
 Necrosis
 Apoptosis
 Intracellular accumulations
 Cell Ageing

4. 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

5.  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

6. 1. Cell membrane integrity
2. Aerobic respiration
3. Protein synthesis
4. Genetic apparatus
Depending on : Type
Duration of Injury
Severity
Adaptability
Injury at one
locus leads to
wide ranging
secondary
effects

7. 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.

8. Ultra-structural
Changes
Light
Microscopy
Changes
Gross
Morphological
Change

9.  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.

10.  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.

11. Injurious
Stimuli
Reversible
stage
ApoptosisNecrosis
Reversible
Cell Injury

12. 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.

13.  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….

14.  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.

15. A
C
T
I
V
A
T
E
S

16. K+ Efflux
Cellular
Swelling

19.  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

21.  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

22. 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