1. Cells are constantly exposed to stresses like hypoxia, toxins, infections, and physical agents that can alter their normal steady state and lead to either reversible injury or irreversible injury and cell death.
2. Reversible injury involves cellular swelling and fatty changes that are potentially reversible if the stressor is removed. Irreversible injury leads to cell death.
3. If cells survive reversible injury, they may adapt through processes like atrophy, hypertrophy, hyperplasia, and metaplasia to better tolerate the stressor. Persistent injury can potentially lead to dysplasia and neoplasia over time.
1. Cellular Injury
dr. Vandy Ikra
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2. Cellular Injury & Adaptation
• Normal cell is in a steady dynamic state
“Homeostasis” :
• The ability or tendency of an organism or cell to
maintain internal equilibrium by adjusting its
physiological processes.
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3. Cells are constantly exposed to stresses.
• Normal physiologic stress
• Severe stresses: injury results, and alters the
normal steady state of the cell, consequently,
• It can survive in a damaged state and adapt to
the injury
(reversible injury or adaptation)
• It can die
(irreversible injury or cell death).
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5. • Hypoxia and ischemia
• Toxins
• Infectious agents
• Immunologic reactions
• Genetic abnormalities
• Nutritional imbalance
• Physical agents
• Aging
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Causes of Cell Injury
6. Causes of Hypoxia
• low levels of oxygen in the air
• poor or absent Hemoglobin function
• decreased erythropoiesis
• respiratory or cardiovascular diseases, or
ischemia (reduced supply of blood)
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Hypoxia & Ischemia
7. • Ischemia & Hypoxia induce mitochondrial
damage.
• This results in decreased ATP which in
turn reduces energy for all cell functions !
• If persistent CELL DEATH
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Toxins
• These include:
o Air pollutants
o Insecticides
o CO
o Asbestos
o Cigarette smoke
o Ethanol
o and Drugs
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Immunologic reactions
• Immune reactions also can result in cell and tissue
injury.
• Example: autoimmune reactions against one’s own
tissues, allergic reactions against environmental
substances, and excessive or chronic immune
responses to microbes.
• In all of these situations, immune responses elicit
inflammatory reactions, which are often the cause of
damage to cells and tissues.
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Genetic abnormalities
• Genetic defects may cause cell injury as a
consequence of deficiency of functional proteins,
such as enzymes in inborn errors of metabolism, or
accumulation of damaged DNA or misfolded
proteins, both of which trigger cell death when
they are beyond repair.
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Nutritional imbalances
• Protein–calorie insufficiency among impoverished
populations remains a major cause of cell injury,
and specific vitamin deficiencies are not
uncommon even in developed countries with high
standards of living.
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Physical agents
• Trauma, extremes of temperature, radiation,
electric shock, and sudden changes in atmospheric
pressure all have wide-ranging effects on cells.
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Aging
• Cellular senescence results in a diminished ability
of cells to respond to stress and, eventually, the
death of cells and of the organism.
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SEQUENCE OF EVENTS IN CELL INJURY AND
CELL DEATH
Reversible Cell Injury
• Reversible injury is the stage of cell injury at which the deranged
function and morphology of the injured cells can return to normal if the
damaging stimulus is removed.
• In reversible injury, cells and intracellular organelles typically become
swollen because they take in water as a result of the failure of energy-
dependent ion pumps in the plasma membrane, leading to an inability
to maintain ionic and fluid homeostasis. In some forms of injury,
degenerated organelles and lipids may accumulate inside the injured
cells.
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The main two morphologic changes in reversible cell
injury are:
• 1. cellular swelling
• 2. fatty change
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Swelling
• Results from failure of the sodium potassium pump due
to ATP depletion
• It is the first manifestation of all forms of injury
• It is reversible
• The organ affected will have increased weight
• Microscopy shows small clear vacuoles within the cytoplasm
this is called hydropic change or vacular degeneration
• The organelles within the cells are also swollen
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Fattychange
• Occurs mainly in hypoxic injury and in toxic and metabolic
injury.
• Microscopy: lipid vacuoles in the cytoplasm
• Seen mainly in cells that participate in fat
metabolism like hepatocytes and myocardial cells
• It is reversible.
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• IF INJURED CELLS DON’T DIE, THEY MAY ADAPT TO
PROTECT THEMSELVES !
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The most common morphologically apparent
adaptive changes are
– Atrophy (decrease in cell size)
– Hypertrophy (increase in cell size)
– Hyperplasia (increase in cell number)
– Metaplasia (change in cell type)
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Atrophy
• Decrease in cell size due to loss of cell substance
(protein degradation & lysosomal proteases digest
extracellular endocytosed molecules )
• Often hormone dependent (insulin, TSH, etc…).
• Atrophic cells have diminished function.
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Hypertrophy
• Hypertrophy is an increase in cell size by gain of cellular
substance
• With the involvement of a sufficient number of cells, an
entire organ can become hypertrophic
• Hypertrophy is caused either by increased functional
demand or by specific endocrine stimulations
• With increasing demand, hypertrophy can reach a limit
beyond which degenerative changes and organ failure
can occur
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Hyperplasia
• Hyperplasia is an increase in the number of cells of
a tissue or organ, from an increased rate of cell
division.
• Hyperplasia may be a predisposing condition to
neoplasia.
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Metaplasia
• Metaplasia is a “reversible” change (adaptation ) in
which one adult cell type is replaced by another
adult cell type that are better suited to tolerate a
specific abnormal environment.
• May occur in epithelial or mesenchymal tissue. e.g.
Bronchial , gastric, & cervical epith., and bone in
injured soft tissue
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Dysplasia
• Abnormal changes in size, shape, appearance, and
organizational structure of the cells
• Sometimes atypical hyperplasia can progress to
neoplasia
• Caused by persistent injury or irritation
• Cervix, oral cavity, gallbladder, and respiratory tract
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REFFERENCE:
• Kumar, V., Abbas, A.K. and Aster, J., 2017. Robbins basic pathology e-
book. Elsevier Health Sciences.
• Khanna, G., 2016. Concise Pathology for Exam Preparation_4e-E-book.
Elsevier Health Sciences.