CELLULAR
ADAPTATIONS
Dr. Kiran H S
Assistant Proffessor
Pathology
Depending on the nature of stimulus/injury, by
cellular responses can be mainly divided into four
types:
1. Cellular adaptations
2. Cell injury
–– Reversible cell injury
–– Irreversible cell injury
3. Intracellular accumulations
4. Pathologic calcification.
OVERVIEW- CELLULAR ADAPTATIONS
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INTRODUCTION
TYPES
MECHANISM
CLINICAL EXAMPLES
INTRODUCTION
Definition:
 Adaptations are reversible changes in the
number, size, phenotype, metabolic
activity, or functions of cells in response to
changes in their environment.
 The cells can achieve a new, steady altered
state that allows them to survive and
continue to function in an abnormal
environment
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Cells must constantly adapt, even under
normal conditions, to changes in their
environment.
These physiological adaptations usually
represent responses of cells to normal
stimulation by hormones or endogenous
chemical substances. For example, as in the
enlargement of the breast and induction of
lactation by pregnancy.
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Pathologic adaptations may share the same
underlying mechanisms, but they provide
the cells with the ability to survive in their
environment and perhaps escape injury.
Then cellular adaptation is a state that lies
intermediate
between
the
normal,
unstressed
cell
and
the
injured,
overstressed cell.
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There are numerous types of cellular adaptations:
Some involve up or down regulation of specific
cellular receptors involved in metabolism of
certain components.
Others are associated with the induction of new
protein synthesis by the target cell.
Other adaptations involve a switch by cells from
producing one type of a family of proteins to
another or markedly overproducing one protein.
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These adaptations then involve all steps of
cellular metabolism of proteins—receptor
binding, signal transduction, transcription,
translation, or regulation of protein packaging
and release.
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In this section we consider some common
adaptive changes in cell growth, size, and
differentiation that underlie many
pathologic processes.
TYPES:
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1) Hypertrophy
2) Hyperplasia
3) Atrophy
4) Metaplasia
1. Hypertrophy:
Definition: An increase in the size of cells,
and with such change, an increase in the
size of the organ.
Left Normal heart
center Hypertrophied heart
Right Hypertrophied and dilated heart
Hypertrophied heart
Normal uterus
gravid uterus
Physiologic hypertrophy of the uterus during pregnancy.A, gross
appearance of a normal uterus (right) and a gravid uterus (left)
that was removed for postpartum bleeding,
（From ROBBINS BASIC PATHOLOGY，2003）
Increased functional demand/workload.
•• Physiological:
 –– Hypertrophy of skeletal muscle: e.g. the bulging
muscles of body builders and athletes.
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–– Hypertrophy of smooth muscle: e.g. growth of the
uterus during pregnancy from estrogenic stimulation.
•• Pathological:
–– Hypertrophy of cardiac muscle: e.g. left
ventricular hypertrophy due to hypertension or
damaged valves (aortic stenosis, mitral
incompetence).
–– Hypertrophy of smooth muscle: e.g.
hypertrophy of urinary bladder muscle in
response to urethral obstruction (e.g. prostate
hyperplasia), hypertrophy of muscular layer of
stomach due to pyloric stenosis.
Mechanisms of Cellular
Hypertrophy
1. Activation of the Signal
Transduction Pathways
 Various mechanisms involved are:
 Physiologic Hypertrophy
•• Mechanical stretch: Increased work
load on the myocardium produces
mechanical stretch and is the major
trigger for physiological hypertrophy.
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Pathologic Hypertrophy
Growth factors and hypertrophy agonists
are involved in pathologic hypertrophy.
•• Growth factors: These include (TGF-β),
insulin-like growth factor-1 (IGF-1), and
fibroblast growth factor (FGF).
•• Hypertrophy agonists: These include αadrenergic agonists, endothelin-I,
angiotensin II, nitric oxide (NO), and
bradykinin.
2. Activation of Transcription Factors
 Mechanical stretch, growth factors and
hypertrophy agonists activate the signal
transduction pathways and transcription
factors (e.g. Myc, Fos, Jun).
 Activated transcription factors results in:
•• Increased synthesis of contractile
proteins
•• Induction of embryonic/fetal genes
•• Increased production of growth factor
2. Hyperplasia
Definition: An increase in the number of cells in an organ or
tissue, which may then have increased volume.
Causes:
1) Physiological hyperplasia: Hormonal stimulation,
or as compensatory process.
 –– Hyperplasia due to hormones: e.g. hyperplasia of
glandular epithelium of the female breast at puberty,
pregnancy and lactation, hyperplasia of the uterus
during pregnancy from estrogenic stimulation.
 –– Compensatory hyperplasia: e.g. in liver following
partial hepatectomy.
2) Pathological hyperplasia: Due to excess
endocrine stimulation or chronic
injury/irritation.
 –– Excessive hormonal stimulation: e.g.
endometrial hyperplasia (due to estrogen
and benign prostatic hyperplasia due to
androgens.
 –– Chronic injury/irritation: Long-standing
inflammation or chronic injury may lead to
hyperplasia especially in skin or oral
mucosa.
Mechanism
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•• Hyperplasia is characterized by cell
proliferation mostly of mature cell mediated
through stimulation by growth factor or
hormones.
•• Some instances, the new cells may be
derived from tissue stem cells.
Morphology
•• Gross: Size of the affected organ is
increased.
•• Microscopy: Increased number of cells with
increased number of mitotic figures.
Left Normal breast
Right Hyperplasia
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Failure of regulation: Pathologic, as in
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Neoplastic: Total loss of normal control
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hyperthyroidism or as in hyperparathyroidism
resulting from renal failure or vitamin D
deficiency.
mechanism. Should not be termed hyperplasia.
Hyperplasia is also an important response of
connective tissue cells in wound healing, in
which proliferating fibroblasts and blood vessels
aid in repair.
The relationship between
hyperplasia and hypertrophy:
Although hypertrophy and hyperplasia are
two distinct processes, frequently both
occur together, and they well be triggered
by the same mechanism.
3. Atrophy
Definition: Acquired loss of size due to reduction of
cell size or number of parenchyma cells in an organ.
Causes:
1)Physiologic: Common during normal fetal
development, and in adult life.
 •• During fetal development: e.g. atrophy of
embryonic structures such as thyroglossal duct.
 •• During adult life: e.g. involution of thymus,
atrophy of brain and heart due to aging (senile
atrophy).
Pathological: Local or generalized.
 1. Local•• Disuse atrophy (decreased workload): e.g.
atrophy of limb muscles immobilized in a plaster
cast (fracture) or after prolonged bed rest.
•• Denervation (loss of innervation) atrophy: e.g.
atrophy of muscle due to damage to the nerves
(poliomyelitis).
•• Ischemic (diminished blood supply) atrophy: e.g.
brain atrophy produced by ischemia due to
atherosclerosis of the carotid artery.
•• Pressure atrophy: e.g. atrophy of renal
parenchyma in hydronephrosis due to increased
pressure.
2. Generalized •• Starvation (inadequate nutrition)
atrophy: e.g. protein-calorie malnutrition.
Mechanisms
 Atrophic cells have diminished function.
There is decreased protein synthesis and
increased protein degradation in cells
Morphology
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•• Gross: The organ is small and often
shrunken.
•• Microscopy: The cells are smaller in
size due to reduction in cell organelles.
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Diminished blood supply:
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Loss of nerve stimulus:
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Loss of endocrine stimulation:
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Inadequate nutrition:
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Pressure:
Atrophy represents a reduction in the
structural components of the cell.
 The cell contains fewer mitochondria,
myofilaments, a lesser amount of
endoplasmic reticulum, and increasing
in the number of autophagy vacuoles.
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Left Normal
Right Atrophy
Atrophy of the brain
(offered by Prof. Orr )
4. Metaplasia
Definition: Metaplasia is a reversible change in
which one adult cell type is replaced by another
adult cell type.
Causes
 •• Metaplasia is usually fully reversible
adaptive response to chronic persistent
injury. If the noxious stimulus is removed
(e.g. cessation of smoking), the metaplastic
epithelium may return to normal.
 •• Metaplasia is mainly seen in association
with tissue damage, repair, and
regeneration.
 •• The replacing cell type is usually more
suited to a change in environment
Squamous metaplasia in bronchitis
（offered by Prof.Orr）
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Types of Metaplasia
1) Epithelial Metaplasia
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Most Common Type
Squamous metaplasia: Original epithelium is
replaced by squamous epithelium.
•• Respiratory tract: e.g. chronic irritation due
to tobacco smoke, the normal ciliated
columnar epithelial cells of the trachea and
bronchi undergo squamous metaplasia.
•• Cervix: Squamous metaplasia in cervix is
associated with chronic infection.
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Columnar metaplasia: Original
epithelium is replaced by columnar
epithelium.
•• Squamous to columnar: In Barrett
esophagus, the squamous epithelium of
the esophagus replaced by columnar
cells.
•• Intestinal metaplasia: The gastric
glands are replaced by cells resembling
those of the small intestine.
2) Connective Tissue Metaplasia
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•• Osseous metaplasia: Formation of
new bone at sites of tissue injury is
known as osseous metaplasia.
Bone formation in muscle, known as
myositis ossificans, occasionally occurs
after intramuscular hemorrhage.
Mechanism
 Develops due to the reprogramming of
precursor cells (i.e. stem cells or
undifferentiated mesenchymal cells)
that are present in normal tissues.
SUMMARY
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