This document discusses cellular injury and adaptation. It notes that cells exist in a state of homeostasis but can become injured by various stressors like hypoxia or toxins. Injuries can be reversible or irreversible. Initial injuries disrupt ATP production and increase intracellular calcium levels, activating damaging enzymes. This can lead to further damage of mitochondria and lysosomes as well as increased reactive oxygen species. Depending on the severity and duration of injury, cells may undergo apoptosis, necrosis, or adaptational changes in an attempt to survive.

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