CELLULAR ADAPTATIONS
These are reversible changes in the
size, number, phenotype, metabolic
activity, or functions of cells in response
to changes in their environment.
Types of adaptations
◦Hypertrophy
◦Hyperplasia
◦Atrophy
◦Metaplasia
Hypertrophy
This is increase in the size of cells with
resultant increase in the size of the organ.
The hypertrophied organ has no new cells, just
larger cells.
The increased size of the cells is due to the
synthesis of more structural components of the
cells.
Hypertrophy occurs in non dividing cells (e.g.,
myocardial fibers)
Cont….
Hypertrophy can be physiologic or
pathologic
Hypertrophy occurs mainly striated muscle
cells of the heart and skeletal muscles
because they have only a limited capacity
for division
The most common stimulus for hypertrophy
of muscle is increased workload
Mechanisms of Hypertrophy
Hypertrophy is the result of increased
production of cellular proteins
Growth factor stimulation
Neuroendocrine stimulation
Ion channels
Other chemical mediators
Oxygen supply
Hypertrophy antagonists
Atrial and B-type natriuretic factors
High concentrations of NO
many other factors either brake or prevent
cell adaptation by hypertrophy.
HYPERPLASIA
Hyperplasia is an increase in the number of
cells in an organ or tissue, usually resulting in
increased mass of the organ or tissue.
Hyperplasia and hypertrophy frequently occur
together
Hyperplasia takes place if the cell population
is capable of dividing
Hyperplasia can be physiologic or pathologic.
Physiologic Hyperplasia
Physiologic hyperplasia can be
divided into
hormonal hyperplasia
compensatory hyperplasia
Hormonal hyperplasia eg
proliferation of the glandular
epithelium of the female breast at
puberty and during pregnancy
Pathologic Hyperplasia
Most forms of pathologic hyperplasia are
caused by excesses of hormones or growth
factors acting on target cells.
Endometrial hyperplasia is an example of
abnormal hormone-induced hyperplasia
pathologic hyperplasia constitutes a fertile soil
in which cancerous proliferation may arise
For instance, patients with hyperplasia of the
endometrium are at increased risk for
developing endometrial cancer
Mechanisms of Hyperplasia
Hyperplasiais the result of growth
factor–driven proliferation of mature
cells
some cases it occurs as a result of
increased output of new cells from tissue
stem cells.
ATROPHY
Atrophy is reduced size of an organ
or tissue resulting from a decrease in
cell size and number.
Atrophy can be physiologic or
pathologic.
Physiologic atrophy is common
during normal development eg
atrophy of notochord and
thyroglossal duct
The decrease in size of uterus after
Pathologic atrophy
This could be localized or generalized
Causes include
Decreased workload (atrophy of
disuse )
Loss of innervation (denervation
atrophy )
Diminished blood supply
Inadequate nutrition
Loss of endocrine stimulation
Pressure.
Cont…..
Cellular changes are identical in all of these
settings.
Initially there is a decrease in cell size and
organelles
In atrophic muscle, the cells contain fewer
mitochondria and myofilaments and a reduced
amount of rough ER.
Achieving balance between metabolic demand
and the lower levels of blood supply, nutrition, or
trophic stimulation, a new equilibrium is reached.
Early in the process atrophic cells may have
diminished function, but they are not dead.
Mechanisms of Atrophy
Atrophy results from decreased protein
synthesis and increased protein degradation
in cells.
The degradation of cellular proteins occurs
mainly by the ubiquitin-proteasome pathway.
Nutrient deficiency and disuse may activate
ubiquitin ligases
This pathway is also thought to be
responsible for the accelerated proteolysis
seen in a variety of catabolic conditions eg
cancer cachexia.
Cont…
In many situations, atrophy is also accompanied
by increased autophagy, with resulting
increases in the number of autophagic vacuole
Some of the cell debris within the autophagic
vacuoles may resist digestion and persist as
membrane-bound residual bodies
An example of such residual bodies is the
lipofuscin granules
When present in sufficient amounts, they
impart a brown discoloration to the tissue
(brown atrophy)
METAPLASIA
Metaplasia is a reversible change
in which one differentiated cell
type (epithelial or mesenchymal)
is replaced by another cell type.
It may represent an adaptive
substitution of cells that are
sensitive to stress by cell types
better able to withstand the
adverse environment
Cont…
The most common epithelial
metaplasia is columnar to squamous
A deficiency of vitamin A (retinoic
acid) induces squamous metaplasia
in the respiratory epithelium
Metaplasia from squamous to
columnar type may also occur, as in
Barrett esophagus
Cont…
Connective tissue metaplasia usually
formation of cartilage, bone, or adipose
tissue (mesenchymal tissues) in tissues
that normally do not contain these
elements
For example, bone formation in muscle,
designated myositis ossificans
This type of metaplasia is less clearly
seen as an adaptive response, and may
be a result of cell or tissue injury.
Mechanisms of Metaplasia
Metaplasia occurs as a result of a
reprogramming of stem cells in normal
tissue or of undifferentiated mesenchyme.
In a metaplastic change, these precursor
cells differentiate along a new pathway
The differentiation of stem cells to a
particular lineage is brought about by
signals generated by cytokines, growth
factors, and extracellular matrix
components in the cells' environment
