This document discusses cell injury and death. It begins by outlining the objectives of explaining cell injury processes, reversible and irreversible injury, and mechanisms of injury like hypoxia and free radicals. It then defines cell injury as occurring when cells can no longer adapt to stressors. The causes, types (reversible and irreversible), and morphological signs of injury are described. The major mechanisms of injury - free radical formation, hypoxia/ATP depletion, and calcium dysregulation - are explained. The document concludes by distinguishing the processes of apoptosis (programmed cell death) and necrosis, and classifying types of necrosis.

1. TRAUMA AND CELL
INJURY
Mr Nasar Khan
Nursing Instructor
ICONM

2. Objectives:
By the end of this presentation, the learner will be
able to:
 Discuss cell injury.
 Explain the process of cell injury.
 Discuss the reversible and irreversible cell
injury.
 Discuss the mechanism of cell injury that is
• Hypoxia
• Free radical
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3. • Chemical
• Physical
• Nutritional
Discuss cell death in terms of:
Mechanism and types of necrosis
Mechanism and significance of apoptosis.
Cont…
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4. Basic concepts
•The cells responds to various stimuli and do their
best to maintain their structure by adapting the new
situation like hypertrophy, atrophy, metaplasia,
dysplasia, hyperplasia.
•But somehow if the stimuli continues there, adaptive
mechanisms of cells fail, resulting into cell injury
that can proceeds to death.
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6. Cell injury
All cells of body have an inbuilt mechanism to deal with
changes in environment to an extent.
OR
If the limits of adaptative mechanisms are exceeded or
when no adaptative response is possible- cell injury
OR
When cells are stressed so severely that no longer able to
adapt.
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7. •The cause of cell injury can be internal or external.
•The cellular response to cell injury depends upon
• Cell type
•Blood supply
•Physical health
•Status of nutrition
•Capacity of regeneration
Cont…
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9. Types of cell injury
 The cell injury can be reversible or irreversible
depending upon the intensity and duration of exposure
of the noxious agent.
 Reversible cell injury: Although impairing cell
function, does not result in cell death. Pathologic
changes that can be reversed when the stimulus is
removed and the cellular injury has been mild. Cell
injury is reversible only up to certain point.
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10. Cont…
 Irreversible cell injury: denotes pathologic changes
that are permanent and cause cell death, they cannot be
reversed to normal state.
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11.  For example: if the blood suply to heart muscles is
cut off for 10-15 minutes- the myocardial cell
experiences injury but it can recover to normal
function, if the blood flow is cut off for longer
period- the myocardial fiber dies-necrosis.
 key point: It is almost impossible to identify the exact
critical point where a reversible injury is transformed
into an irreversible injury
Cont…
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12. Reversible (or irreversible) morphological sign of
damage include formation of
 Cell blebs
Cell surface deformity most likely caused by disorderly
function of cytoskeleton.
 Myelin fibers
Wart like structure probably originating from
membrane damage.
Cont…
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13. ATP depletion
ATP is required for important processes inside
the cells like membrane transport, protein
synthesis, and lipogenesis; thus, its depletion
causes significant damage to the cell.
Cont…
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16. CAUSES OF CELL INJURY:
 Cell damage can occur in many ways. For purposes
of discussion, the ways by which cells are injured
have been grouped into five categories:
1. Physical agent (extremes of temperature, electrical
injuries, burn, trauma)
2. Radiation
3. Chemical agent (drugs, arsenic poisoning, mercury
poisoning)
4. Biologic agent (virus, protozoa, fungi)
5. Nutritional imbalance (Vitamins deficiency, protein
deficiency). TRAUMA & CELL INJURY 16

17. MECHANISM OF CELL INJURY
 There are three major mechanism whereby most
injurious agents exert their effects:
 Free radical formation
 Hypoxia and ATP depletion
 Disruption of intracellular calcium homeostasis
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19. Cont…
1. Free radical injury: They are a chemical species
that possess an unpaired electron in the outer orbit
(valence shell) of the molecule. The unpaired
electron causes free radicals to be unstable and
highly reactive, so that they react nonspecifically
with molecules in the sorroundings.
Free radicals react with proteins, lipids, and
carbohydrates, thereby damaging cell membranes;
inactivate enzymes; and damage nucleic acids that
make up DNA.
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20.  Free Radicals can also involve in DNA breakage.
 When these free radicals are in small amount the
cells have some antioxidants (vitamin A,C,E)
which neutralize these radicals and when it gets
higher it causes oxidative stress.
 Causes are reduction oxidation reaction, x-rays,
UV lights or inflammation etc.
Cont…
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22. 2. HYPOXIA
•Hypoxia can result from an inadequate amount of
oxygen in air (oxygen depriviation).
•Decrease blood flow (ischemia)
•Inability of cells to use oxygen.
Early stage
•Affect mitochondria →decreased oxidative
phosphorylation and ATP synthesis
•Decreased ATP availability
Failure of the cell membrane pump
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23. • Increase intracellular Na+ and water decrease
intracellular K+ →cellular swelling and
swelling of organelles.
• Swelling of endoplasmic
• Swelling of mitochondria
 Disaggregation of ribosome and failure of
protein synthesis
Cont…
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24. •Result an increase glycolysis.
•Accumulation of lactate.
•Decreased intracellular PH.
•Acidification causes reversible clumping of nuclear
chromatin.
 Late stage
• Membrane damage.
• lysosomal and other organelle membrane
phospholipids.
Cont…
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26. Depletion of ATP
Na+K+ATPase (Na-pump),
Ca2+Mg2+ATPases (Ca-pump)
Causes
Hypoxia, Ischemia
Chemical Injury
Membrane
transport
Protein synthesis,
Lipogenesis etc
ATP
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29. 3. Impaired calcium homeostasis:
 In ICF Ca2+ levels are very low that is maintained by
Ca2+-Mg2+ ATPase pump.
 If there is oxygen deficiency (ischemia) the
membrane permeability is altered Ca2+-Mg2+ ATPase
pump stop functioning. Thus Ca2+ moves from
mitochondria, endoplasmic reticulum and ECF to
ICF.
 This increasing levels of Ca2+ leads to alteration in
enzyme activity (phospholipases, proteases,
ATPases,endonucleases).
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30. Alteration in enzymes activivity results in cell
degradation:
• Phospholipases degrade membrane phospholipids;
• Proteases break down membrane and cytoskeleton
proteins;
• ATPases ATP depletion;
• And endonucleases are associated with chromatin
fragmentation.
Cont…
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32. Cell Death
 When the injury to the cell is irreparable, it
will eventually lead to cell death.
 There are two important patterns of cell death.
1. Apoptosis
2. Necrosis
Cont…
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34. Apoptosis, or programmed cell death, is a highly
regulated process that allows a cell to self-degrade in
order for the body to eliminate unwanted or
dysfunctional cells.
The morphological
features of apoptosis
include:
 Cell shrinkage
 Chromatin condensation
and fragmentation
APOPTOSIS
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35.  Formation of cytoplasmic blebs
and apoptotic bodies.
 Phagocytosis of apoptotic
bodies by adjacent healthy cell or
Macrophages.
 Lack of inflammation
 For example, the differentiation of fingers and toes
in a developing human embryo occurs because cells
between the fingers apoptose; the result is that the
digits are separate.
Cont…
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36.  Unlike necrosis, where the cell dies by swelling and
bursting its content in the area, which causes an
inflammatory response, apoptosis is a very clean and
controlled process where the content of the cell is
kept strictly within the cell membrane as it is
degraded .
 The apoptotic cell will be phagocytosed by
macrophages before the cell’s contents have a chance
to leak into the neighborhood.
Cont…
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37. PROCESS OF APOPTOSIS
•During apoptosis, the cells almost start the death cycle
by activating the endogenous enzymes which results in
cell shrinkage, disrupted cytoskeleton, condensation of
cytoplasmic organelle, wrinkling of cell membrane,
clumping of nuclear DNA, shrinkage of nucleus and
nuclear fragmentation and finally a cell divides into
multiple fragments covered with a membrane. Then
these fragments are engulf by phagocytic cells with
complete degradation .
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42.  Necrosis: refers to cell death in an organ or tissue
that is still part of a living person.
 Necrosis differs from apoptosis in that it involves.
 Unregulated enzymatic digestion of cell components.
 Loss of cell membrane integrity with uncontrolled
release of products of cell death into intracellular
space.
 Initiation of inflammatory response.
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43. Classification of necrosis
1. Coagulation necrosis
 In coagulation necrosis, there is acidosis, enzymes are
denatured, structural proteins are impaired as
observed in ischemia or during infarction.
 It is the common pattern of ischemic necrosis. It
occurs in myocardium, kidney, liver and other organs.
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44. Kidney Coagulative necrosis
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45. 2. Liquefaction necrosis(form of necrosis in dead
tissue turns into liquid substance)
 Is a type of necrosis which is characteristic of
bacterial or fungal infections. In liquefactive
necrosis, the affected cell is completely digested by
hydrolytic enzymes, resulting in a soft,
circumscribed lesion consisting of pus and the fluid
remains of necrotic tissue.
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46. 3. Caseous necrosis
 The caseous necrosis is associated with cell lesions and
results from immune mechanisms.
 It appear as soft, friable, cheesy material.
It is characteristic of TB infection.
4. Enzymatic fat necrosis
is a form of necrosis characterized by the action upon fat by
digestive enzymes.
 In fat necrosis the enzyme lipase releases fatty acids from
triglycerides. The fatty acids then complex with calcium
to form soaps. These soaps appear as white chalky
deposits
 It is usually associated with trauma of the pancreas or
acute pancreatitis.
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48. References
• Norris, T. L. (2019). Porth's Pathophysiology Concepts of Altered
Health States (Tenth Edition ed.). Philadelphia: Wolters Kluwer
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