Cell injury can occur through several mechanisms: 1. ATP depletion or hypoxia disrupts cellular energy production, impairing cell functions and compromising cell membranes. 2. Loss of calcium ion homeostasis activates enzymes that damage cells and increases oxidative stress. 3. Excess reactive oxygen species produced during normal cell processes accumulate and react with essential components like lipids, proteins, and DNA, potentially disrupting cell functions. 4. Damage to mitochondria and increased permeability of membranes reduces ATP production, disturbs calcium balance, generates more reactive oxygen species, and can trigger cell death pathways.

1. Pathogenesis of Cell Injury
Dr. Satheesh S,Pharm.D.,
Associate Professor
Department of Pharmacy Practice

2. Pathogenesis of Cell Injury
1. ATP depletion or Hypoxia
2. Loss of Calcium Ions
3. Oxidative Stress (Excess Reactive Oxygen Species)
4. Damage to mitochondria, and increased permeability of membranes

3. ATP depletion or Hypoxia
● Hypoxia, or lack of oxygen, messes with the energy-making process in our
cells, specifically in mitochondria, making less ATP, which is like fuel for our
cells.
● When ATP levels drop, it's like a power outage affecting many cell functions,
causing a lot of problems inside the cell.
● For instance, cells like neurons and heart muscle cells get hurt quickly when
ATP levels fall because their energy supply gets disrupted. The cell walls'
control mechanisms weaken, making them more vulnerable to damage.

4. ATP depletion or Hypoxia
● Low ATP leads to more breakdown of sugars without oxygen, making lactic
acid build up. This makes the cell's environment more acidic, which isn’t
good for its functions.
● When ATP decreases, pumps that help maintain the right balance of
minerals like sodium and potassium in and out of the cell slow down. This
imbalance causes sodium and water to enter the cell, making it swell up.
● Mitochondria, the energy factories of the cell, get affected during hypoxia.
They can't produce enough ATP due to the lack of oxygen and
phosphorylation, a process crucial for energy generation.

5. ATP depletion or Hypoxia
● ATP acts like a battery for the cell, powering up various tasks. Without
enough ATP, these tasks slow down or stop, impacting the cell's ability to
function properly.
● Neurons, the cells in our brain and nervous system, and cardiac myocytes,
the cells in our heart muscle, are highly sensitive to ATP shortages. Their
functions are heavily dependent on a consistent energy supply.
● One significant issue arising from low ATP levels is the compromised cell
wall. It becomes leaky due to reduced activity in pumps fueled by ATP,
causing the cell's interior stability to weaken.

6. ATP depletion or Hypoxia
● The drop in ATP forces the cell to rely more on a backup process called
anaerobic glycolysis, producing lactic acid as a byproduct. This acid builds
up, making the cell's internal environment more acidic.
● The acidity resulting from increased lactic acid can mess with the cell's
usual operations, affecting its ability to function normally and carry out
necessary tasks.
● The pumps responsible for balancing sodium and potassium levels in and
out of the cell don’t work properly when ATP is low. This imbalance leads to
sodium and water flooding into the cell.

7. ATP depletion or Hypoxia
● Increased sodium and water inside the cell cause it to swell, altering its
normal shape and potentially interfering with its functions.
● This cell swelling can lead to further issues, affecting neighboring cells and
disrupting the overall tissue or organs functionality.

8. Loss of Calcium Ions
● Inside the cell, calcium levels are usually kept much lower than outside.
This controlled balance, maintained by structures like mitochondria and the
endoplasmic reticulum, is critical for normal cell function.
● When calcium levels inside the cell rise unexpectedly, it triggers a series of
events that can lead to significant issues in cell function and health.
● One effect of increased calcium levels is the excessive release of a
neurotransmitter called glutamate, which can disrupt communication
between cells, affecting various bodily functions.

9. Loss of Calcium Ions
● Elevated calcium also activates enzymes like proteases and lipases, which
are responsible for breaking down proteins and fats. This activation can
damage the cell membrane, compromising its integrity.
● Moreover, increased calcium levels trigger the activation of molecules like
nitric oxide and reactive oxygen species, which are involved in oxidative
stress, essentially causing harm to the cell.
● When calcium rises unexpectedly, it can disrupt the normal balance within
the cell, potentially leading to an excessive release of certain chemicals that
affect cell communication.

10. Loss of Calcium Ions
● The activation of enzymes due to heightened calcium levels can harm the
cell's outer layer, making it vulnerable to damage and potentially affecting
its function.
● In addition to damaging the cell membrane, increased calcium activates
molecules that promote oxidative stress, essentially adding to the burden
on the cell and impacting its health.
● Maintaining lower calcium levels inside the cell is crucial for its normal
function. When this balance is disrupted, it can set off a chain reaction of
harmful events within the cell.

11. Loss of Calcium Ions
● The sudden rise in calcium inside the cell not only disrupts its internal
balance but also activates processes that can harm the cell's outer structure
and increase oxidative stress, posing a threat to its well-being.

12. Oxidative Stress (Excess Reactive Oxygen Species)
● During regular cellular activities, as cells convert oxygen into water, they
produce reactive forms known as reactive oxygen species (ROS) as a side
effect.
● These reactive oxygen species are essentially 'waste products' generated
during the normal breakdown of oxygen in cells.
● However, these reactive oxygen species are quite reactive and can cause
harm if they accumulate excessively or if the cell's defense mechanisms
can't handle them effectively.

13. Oxidative Stress (Excess Reactive Oxygen Species)
● Reactive oxygen species can react with and harm essential components
within the cell, such as lipids (fats), proteins, and the DNA, which is like the
cell's instruction manual.
● Lipids, which help form the cell's outer layer, proteins that carry out various
functions, and the DNA, which holds crucial genetic information, are all
vulnerable to damage caused by reactive oxygen species.
● The damage caused by reactive oxygen species can disrupt the normal
functions of lipids, proteins, and DNA, affecting the cell's overall
performance.

14. Oxidative Stress (Excess Reactive Oxygen Species)
● Cells have defense mechanisms, like antioxidants, to neutralize these
harmful reactive oxygen species and prevent excessive damage.
● However, when cells are under stress or when there's an imbalance
between reactive oxygen species production and the cell's ability to
neutralize them, it can lead to oxidative stress.
● Oxidative stress occurs when there's an overload of reactive oxygen species
and the cell's defense mechanisms are overwhelmed, potentially causing
more damage to vital cellular components.

15. Oxidative Stress (Excess Reactive Oxygen Species)
● The harmful effects of reactive oxygen species on lipids, proteins, and DNA
can lead to cell dysfunction or even cell death if not properly controlled.

16. Damage to mitochondria, and increased permeability of membranes
● Mitochondria, crucial cellular structures, often become key targets when
cells are harmed by various agents. Changes in their membrane's
permeability can trigger a process called apoptosis, a programmed form of
cell death. Additionally, damage to the plasma membrane affects its ability
to maintain the right balance of ions inside and outside the cell.

17. Damage to mitochondria, and increased permeability of membranes
● Within mitochondria, several critical functions are affected when they're
under stress:
a. There's a reduction in the production of ATP, which serves as energy for the cell's activities.
This decrease can impact the cell's ability to function properly.
b. The balance of calcium within the cell, especially within the endoplasmic reticulum, gets
disrupted, causing an accumulation of calcium inside the cell. This imbalance can disturb
normal cell processes.
c. The generation of reactive oxygen species (ROS) increases. These reactive molecules can
cause harm to cellular components, contributing to cell damage.

18. Damage to mitochondria, and increased permeability of membranes
d. All these mechanisms together have the potential to harm the cell, leading to cellular injury
and compromising its normal functioning. Essentially, the damage to mitochondria and the
resultant disturbances in cellular processes can lead to significant harm within the cell.