Types of cell injury

• There are two (2) types of cell injury:

1. Reversible cell injury.

2. Irreversible cell injury.
 Reversible cell injury
• In early stages or mild forms of injury, the functional
and morphologic changes are reversible if the
damaging stimulus is removed.
• The injury has typically not progressed to severe
membrane damage and nuclear dissolution.
– Eventhough there may be significant structural and
functional abnormalities.
 Reversible cell injury cont…
• The two (2) main morphologic correlates of
reversible cell injury are:
1. Cellular swelling.
2. Fatty change.
 Cellular swelling
• Results from failure of energy-dependent ion
pumps in the plasma membrane, leading to an
inability to maintain ionic and fluid homeostasis.
• When cellular swelling affects many cells in an
organ, the organ will:
– Have some pallor (as a result of compression of
capillaries).
– Increase in turgor.
– Increase in weight.
• Microscopic examination findings:
– Small, clear vacuoles within the cytoplasm.
Cellular swelling cont…

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 Fatty change
• Fatty change is principally encountered in cells
participating in fat metabolism or depend on fat
metabolism (e.g., hepatocytes, myocardial cells).
• It is manifested by the appearance of lipid vacuoles
in the cytoplasm.
• Injured cells may also show increased eosinophilic
staining in the cytoplasm.
• Fatty change also called steatosis.
 Fatty change cont…
• Lipid vacuoles
(round and whitish)
• Increased eosinophilic
staining in the cytoplasm
(pinkish)

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 Intracellular changes in reversible
cell injury
The intracellular changes (ultrastructure findings)
associated with reversible injury include:
1. Plasma membrane alterations such as blebbing,
blunting, or distortion of microvilli, and loosening
of intercellular attachments.
2. Mitochondrial swelling.
3. Appearance of phospholipid-rich amorphous
densities (amorphous black substances) in the
mitochondria.
 Intracellular changes in reversible
cell injury cont…
4. Dilation of the endoplasmic reticulum with
detachment of ribosomes and dissociation of
polysomes.
5. Nuclear alterations, with clumping of chromatin.
6. The cytoplasm may contain phospholipid masses,
called myelin figures, which are derived from
damaged cellular membranes.
Intracellular changes in reversible
cell injury cont…

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 Irreversible cell injury
• Two phenomena consistently characterize
irreversibility:
1. The inability to correct mitochondrial dysfunction.
o Causing lack of oxidative phosphorylation and ATP
generation.
2. Profound disturbances in membrane function.
o Injury to lysosomal membranes results in the enzymatic
dissolution of the injured cell.
o This is followed by necrosis type of cell death.
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 Mechanisms of cell injury
• The biochemical mechanisms linking any given
injury with the resulting cellular and tissue
manifestations are:
– Complex.
– Interconnected.
– Tightly interwoven with many intracellular metabolic
pathways.
 Cellular targets for injurious stimuli

• Genetic apparatus of the cell (DNA).

• Mitochondria (site for ATP production).
• Protein synthesis (Ribosomes detachment from
endoplasmic reticulum).
• Cell membranes.
– Plasma membrane
– Organelle membrane (lysosomes, mitochondrial).
• Cytoskeleton.
 General principles of cell injury responses
i. The cellular response to injurious stimuli depends
on the type of injury, its duration, and its severity.
ii. The consequences of an injurious stimulus depend
on the type, status, adaptability, and genetic
makeup of the injured cell.
iii. Cell injury results from functional and
biochemical abnormalities in one or more of
several essential cellular components.
iv. Multiple biochemical alterations may be triggered
by any one injurious insult.
Important biochemical mechanisms of
cell injury
1. ATP depletion.
2. Mitochondrial damage.
3. Increase calcium entry into the cell (Influx of
calcium).
4. Reactive oxygen species accumulation.
5. Cell membrane damage.
6. Misfolded proteins and DNA damage.
 Other cellular alterations during cell
injury
A. Abnormal deposits of materials in cells and
tissues are the result of excessive intake or
defective transport or catabolism.
1. Depositions of lipids.
– Fatty change.
– Cholesterol deposition.
2. Deposition of proteins.
– Reabsorbed proteins in kidney tubules.
– Immunoglobulins in plasma cells.
 Other cellular alterations during
cell injury
3. Deposition of glycogen
– In glycogen storage disease.
4. Deposition of pigments
– Carbon, lipofuscin (breakdown product of lipid
peroxidation).
– Iron (due to overload, or in hemosiderosis).
Other cellular alterations during cell
injury
B. Pathologic calcifications.
i. Dystrophic calcification.
– Deposition of calcium at sites of cell injury and necrosis.
ii. Metastatic calcification.
– Deposition of calcium in normal tissues, caused by
hypercalcemia (usually a consequence of parathyroid
hormone excess).

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Ischemia-reperfusion injury
• This occurs when there is restoration of blood flow
to ischemic but viable tissues results,
paradoxically, in the death of cells that are not
otherwise irreversibly injured.
• Thus reperfusion after ischemic state paradoxically
deteriorates the already injured cell.
• This is a clinically important process that may
contribute significantly to tissue damage in
myocardial and cerebral ischemia.
Ischemia-reperfusion injury
• Mechanisms that may account for the exacerbation
of cell injury resulting from reperfusion into
ischemic tissues:
i. New damage may be initiated during
reoxygenation by increased generation of reactive
oxygen species.
ii. The inflammation that is induced by ischemic
injury may increase with reperfusion.
iii. Activation of the complement system may also
contribute to ischemia-reperfusion injury.
 Key points
• Hypoxia is the commonest cause of the cell injury.
• Cell injury can reversible or irreversible.
• The main morphological changes seen in reversible
cell injury are cellular swelling and fatty change.
• Profound mitochondrial dysfunction and membrane
damage exacerbate irreversible cell injury.
• ATP depletion is the most common biochemical
mechanism of cell injury.

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 Evaluation
1. What are the causes of cell injury?
2. What are the intercellular structural changes seen in
reversible cell injury?
3. Mention mechanisms involved in cell injury
4. Define ischemic-reperfusion injury.
5. List four (4) structural changes of reversible cell
injury.

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 References
• Kumar V.; Abbas A. K.; Aster J. C.;(2013): Robbins
and Contran Pathologic Basis of Disease (9th Ed.)
Elsevier Saunders, China. Pg. 1, 6-9.
• Mohan H.;(2010): Text book of Pathology (6th Ed.)
Jaypee Brothers Medical Publishers, India . Pg. 21,
27-43.

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