Cell Injury and Adaptation 3-1

Cell Injury
And
Adaptation
Lecture 3
Dr. Alaa Shamikh
Factors that influence the cell injury
The cellular response to injurious stimuli depends on:
1. The type of injury.
2. Duration of injury.
3. Severity of the injury.
 low doses of toxins or a brief period of ischemia may lead to

reversible cell injury, whereas larger toxin doses or longer
ischemic times may result in irreversible injury and cell death.
MECHANISMS
OF
CELL INJURY
AND
CELL DEATH
Mechanisms of cell injury and cell death
A. Ischemia-Reperfusion Injury: this occur because of the

following
1. In ability of the mitochondria to completely reduce the oxygen

thus production of the ROS with resultant oxidative stress.
• ROS causes cell injury by damaging multiple component of
cells.
I. Lipid peroxidation of membranes.
II. Crosslinking and other changes in proteins.
III.DNA damage.
2. Inflammation that is induced by ischemic injury may increase

with reperfusion because it enhances the influx of leukocytes and
plasma proteins.
B. Cell Injury Caused by Toxins
I. Direct-acting toxins.
Ex. 1. Mercuric chloride poisoning.
2. Many anti-neoplastic chemotherapeutic agents.
3.Toxins made by microorganisms.
II. Latent toxins: Many toxic chemicals are not intrinsically active
but must first be converted to reactive metabolites, which then
act on target cells.
C. Endoplasmic Reticulum Stress
 The accumulation of misfolded proteins in a cell can stress
compensatory pathways in the ER and lead to cell death by
apoptosis.
 Intracellular accumulation of misfolded proteins may be caused

by abnormalities that increase the production of misfolded
proteins or reduce the ability to eliminate them.
 Protein misfolding is recognized as a feature of a number of

diseases, including the neurodegenerative disorders Alzheimer
disease, and Parkinson disease, and may underlie type 2 diabetes
as well.
 improperly folded proteins can also accumulate in extracellular

tissues, as in amyloidosis.
D. DNA Damage
Exposure of cells to radiation or chemotherapeutic agents,

intracellular generation of ROS, and acquisition of mutations may
all induce DNA damage, which if severe may trigger apoptotic
death.
E. Inflammation
Inflammatory cells, including neutrophils,

macrophages, lymphocytes, and other leukocytes,
secrete products that evolved to destroy microbes but
also may damage host tissues.
As what happen in the autoimmune diseases and

allergies.
CELLULAR ADAPTATIONS
TO
STRESS
Adaptation
 Adaptations are reversible changes in the number, size, phenotype, metabolic activity, or
functions of cells in response to changes in their environment.
Adaptation includes the following types
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
A. Hypertrophy
 Hypertrophy is an increase in the size of cells resulting in an

increase in the size of the organ.
 Hypertrophy occurs when cells have a limited capacity to

divide.
 Hypertrophy and hyperplasia also can occur together, and

obviously both result in an enlarged organ.
 Hypertrophy can be physiologic or pathologic and is caused

either by increased functional demand or by growth factor or
hormonal stimulation.
A. Hypertrophy
I. Physiologic hypertrophy: The massive

physiologic enlargement of the uterus
during pregnancy occurs as a consequence
of estrogen stimulated smooth muscle
hypertrophy and smooth muscle
hyperplasia.
A. Hypertrophy
II. Pathologic hypertrophy: is the cardiac

enlargement that occurs with hypertension or
aortic valve disease.
B. Hyperplasia
Hyperplasia is an increase in the number of cells in an organ

that stems from increased proliferation, either of differentiated
cells or, in some instances, less differentiated progenitor cells.
Physiologic hyperplasia
Pathologic hyperplasia
Physiologic hyperplasia
1) Hormonal hyperplasia: exemplified by the proliferation of

the glandular epithelium of the female breast at puberty and
during pregnancy.
2) Compensatory hyperplasia: in which residual tissue grows

after removal or loss of part of an organ. For example, when
part of a liver is resected, mitotic activity in the remaining
cells begins as early as 12 hours later, eventually restoring
the liver to its normal size.
Pathologic hyperplasia
 pathologic hyperplasia are caused by excessive hormonal or growth factor

stimulation.
EX. 1. Endometrial hyperplasia in response to estrogen over

stimulation.
2. Stimulation by growth factors also is involved in the

hyperplasia that is associated with certain viral infections;
for
example, papillomaviruses cause skin warts and mucosal
lesions that are composed of masses of hyperplastic
epithelium.
 An important point is that in all of these situations, the hyperplastic process

remains controlled; if the signals that initiate it abate, the hyperplasia
disappears.
C. Atrophy
 Shrinkage in the size of the cell by the loss of cell substance is

known as atrophy.
 When a sufficient number of cells is involved, the entire tissue

or organ diminishes in size, becoming atrophic.
 It should be emphasized that although atrophic cells may have

diminished function, they are not dead.
 Causes of atrophy include a decreased workload (e.g.,

immobilization of a limb to permit healing of a fracture), loss of
innervation, diminished blood supply, inadequate nutrition,
loss of endocrine stimulation, and aging (senile atrophy).
C. Atrophy
 Although some of these stimuli are physiologic (e.g., the loss of

hormone stimulation in menopause) and others pathologic (e.g.,
denervation), the fundamental cellular changes are identical.
 Atrophy results from decreased protein synthesis and increased

protein degradation in cells.
 In many situations, atrophy is also accompanied by increased

autophagy, with resulting increases in the number of autophagic
vacuoles.
 Autophagy ("self-eating") is the process in which the starved

cell eats its own components in an attempt to find nutrients and
survive.
D. Metaplasia
 Metaplasia is a reversible change in which one adult cell type

(epithelial or mesenchymal) is replaced by another adult cell
type.
 In this type of cellular adaptation, cells sensitive to a particular

stress are replaced by other cell types better able to withstand the
adverse environment.
 Metaplasia is thought to arise by genetic "reprogramming" of

stem cells rather than trans differentiation of already
differentiated cells.
D. Metaplasia
 Epithelial metaplasia is exemplified by the squamous change

that occurs in the respiratory epithelium in habitual cigarette
smokers.
 The normal ciliated columnar epithelial cells of the trachea

and bronchi are focally or widely replaced by stratified
squamous epithelial cells.
 The "rugged" stratified squamous epithelium may be able to

survive under circumstances that the more fragile specialized
epithelium would not tolerate.
D. Metaplasia
 Although the metaplastic squamous epithelium has survival

advantages, important protective mechanisms are lost, such as
mucus secretion and ciliary clearance of particulate matter.
 The influences that induce metaplastic transformation, if

persistent, may predispose to malignant transformation of the
epithelium.
D. Metaplasia
 It is thought that cigarette smoking initially causes squamous metaplasia, and

cancers arise later in some of these altered foci.
 Metaplasia may also occur in mesenchymal cells but less clearly as an

adaptive response.
 For example, bone is occasionally formed in soft tissues, particularly in foci

of injury.
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Cell Injury

The cellular response to injurious stimuli depends on:

1. The type of injury.

3. Severity of the injury.

 low doses of toxins or a brief period of ischemia may lead to

A. Ischemia-Reperfusion Injury: this occur because of the

1. In ability of the mitochondria to completely reduce the oxygen

2. Inflammation that is induced by ischemic injury may increase

2. Many anti-neoplastic chemotherapeutic agents.

3.Toxins made by microorganisms.

 Intracellular accumulation of misfolded proteins may be caused

 Protein misfolding is recognized as a feature of a number of

 improperly folded proteins can also accumulate in extracellular

Exposure of cells to radiation or chemotherapeutic agents,

Inflammatory cells, including neutrophils,

As what happen in the autoimmune diseases and

Adaptation includes the following types

 Hypertrophy is an increase in the size of cells resulting in an

 Hypertrophy occurs when cells have a limited capacity to

 Hypertrophy and hyperplasia also can occur together, and

 Hypertrophy can be physiologic or pathologic and is caused

I. Physiologic hypertrophy: The massive

II. Pathologic hypertrophy: is the cardiac

Hyperplasia is an increase in the number of cells in an organ

1) Hormonal hyperplasia: exemplified by the proliferation of

2) Compensatory hyperplasia: in which residual tissue grows

 pathologic hyperplasia are caused by excessive hormonal or growth factor

EX. 1. Endometrial hyperplasia in response to estrogen over

2. Stimulation by growth factors also is involved in the

 An important point is that in all of these situations, the hyperplastic process

 Shrinkage in the size of the cell by the loss of cell substance is

 When a sufficient number of cells is involved, the entire tissue

 It should be emphasized that although atrophic cells may have

 Causes of atrophy include a decreased workload (e.g.,

 Although some of these stimuli are physiologic (e.g., the loss of

 Atrophy results from decreased protein synthesis and increased

 In many situations, atrophy is also accompanied by increased

 Autophagy ("self-eating") is the process in which the starved

 Metaplasia is a reversible change in which one adult cell type

 In this type of cellular adaptation, cells sensitive to a particular

 Metaplasia is thought to arise by genetic "reprogramming" of

 Epithelial metaplasia is exemplified by the squamous change

 The normal ciliated columnar epithelial cells of the trachea

 The "rugged" stratified squamous epithelium may be able to

 Although the metaplastic squamous epithelium has survival

 The influences that induce metaplastic transformation, if

 It is thought that cigarette smoking initially causes squamous metaplasia, and

 Metaplasia may also occur in mesenchymal cells but less clearly as an

 For example, bone is occasionally formed in soft tissues, particularly in foci

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