Cellular adaptations include reversible changes in cells' size, number, phenotype, or functions in response to environmental changes. Physiologic adaptations represent responses to normal stimulation, while pathologic adaptations allow cells to avoid injury but compromise normal function. Common cellular adaptations include: - Atrophy, a shrinkage in cell size from loss of substance. - Hypertrophy, an increase in cell size from increased organelles and proteins. - Hyperplasia, an increase in cell number through cell division. - Metaplasia, replacement of one adult cell type with another better suited to stresses. - Dysplasia, disordered cell development with proliferation and cytologic changes that can progress to carcinoma

1. Cellular Adaptation
HNS 2201: HUMAN PATHOLOGY

2. Cellular Adaptations
 Adaptations are reversible changes in the number, size, phenotype, metabolic
activity, or functions of cells in response to changes in their environment.
 Physiologic adaptations usually represent responses of cells to normal
stimulation by hormones or endogenous chemical mediators (e.g., the
hormone-induced enlargement of the breast and uterus during pregnancy), or
to the demands of mechanical stress (in the case of bones and muscles).
 Pathologic adaptations are responses to stress that allow cells to modulate
their structure and function and thus escape injury, but at the expense of normal
function, such as squamous metaplasia of bronchial epithelium in smokers.

3. Introduction
 Cells adapt to internal environment just as the total organism adapt to external
environment
 Adaptation maybe by changes in>>
 Size
 Number
 Type
 Or
 Combination
 This leads to cellular
 Atrophy
 Hypertrophy
 Hyperplasia
 Metaplasia
 dysplasia

4. Atrophy
 Atrophy is shrinkage in the size of cells by the
loss of cell substance.
 When a sufficient number of cells are involved, the
entire tissue or organ is reduced in size, or atrophic .
Although atrophic cells may have diminished function,
they are not dead.
 Cellular atrophy results from a combination of
decreased protein synthesis and increased protein
degradation

7. Atrophy
 Atrophied cells…
 Reduce their oxygen consumption
 Other cellular functions
By….decreasing the number and size of their organelles

8. Causes Of Atrophy
A. Physiologic atrophy: a normal process of aging in some
tissues, which could be due to loss of:
 Endocrine stimulation
 arteriosclerosis
For example:
 Atrophy of lymphoid tissue in lymph nodes, appendix and
thymus
 Atrophy of gonads after menopause
 Atrophy of brain with aging

9. Causes Of Atrophy
B. Pathologic atrophy: the causes are as under:
1. Starvation atrophy: there is first depletion of
carbohydrate and fat stores followed by protein catabolism.
There is general weakness, emaciation and anemia referred to
as cachexia seen in cancer and severely ill patients
2. Ischaemic atrophy: Gradual diminution of blood
supply due to atherosclerosis may result in shrinkage of the
affected organ
e.g.
i) Small atrophic kidney in atherosclerosis of renal artery
ii) Atrophy of brain in cerebral atherosclerosis

10. Causes Of Atrophy
B. Pathologic atrophy Cont..
3.Disuse atrophy: Prolonged diminished functional activity is
associated with disuse atrophy of the organ
e.g.
i) Wasting of muscles of limb immobilized in cast.
ii) Atrophy of .the pancreas in obstruction of pancreatic
duct.
4. Neuropathic atrophy: Interruption in nerve supply
leads to wasting of muscles
e.g.
 i) Poliomyelitis
ii) Motor neuron disease
iii) Nerve section

11. Causes Of Atrophy
B. Pathologic atrophy Cont..
5. Endocrine atrophy: Loss of endocrine regulatory
mechanism results in reduced metabolic activity of tissues and
hence atrophy
e.g.
i) Hypopituitarism may lead to atrophy of thyroid, adrenal
and gonads
ii) Hypothyroidism may cause atrophy of the skin and its
adnexal structures.

12. Causes Of Atrophy
B. Pathologic atrophy Cont..
6. Pressure atrophy: Prolonged pressure from benign
tumors or cyst or aneurysm may cause compression and atrophy of
the tissues
e.g.
i) Erosion of spine by tumor in nerve root
ii) Erosion of skull by meningioma arising from piaarachnoid
iii) Erosion of sternum by aneurysm of arch of aorta
7. Idiopathic atrophy: There are some examples of atrophy
where no obvious cause is present
e.g.
i) Myopathies
ii) Testicular atrophy

13. Hypertrophy
 An increase in cell size and an increase in the functioning tissue
mass
 Stated another way, in pure hypertrophy there are no new
cells, just bigger cells containing increased amounts of
structural proteins and organelles.
 Results in an increase in tissue mass
 Seen in cardiac, skeletal, and muscle tissue
 These cells are not capable of mitosis (so, no  number or
hyperplasia)
 May be a normal physiologic response
 as seen in an increase in muscle size with exercise

14.  Hyperplasia is an adaptive response in cells capable of
replication, whereas 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

15. Hypertrophy
15

16. hyperplasia
16

17. • Hypertrophy can be physiologic or pathologic and is caused either by
increased functional demand or by growth factor or hormonal
stimulation.
PHYSIOLOGIC HYPERTROPHY
1.The massive physiologic enlargement of the uterus during pregnancy occurs as a
consequence of estrogen stimulated smooth muscle hypertrophy and smooth muscle
hyperplasia
2. In contrast, in response to increased workload the striated muscle cells in both the
skeletal muscle and the heart undergo only hypertrophy because adult muscle cells have
a limited capacity to divide.

18. Hypertrophy
Pathologic hypertrophy
Examples:
1. Hypertrophy of cardiac muscle: may occur in:
Systemic hypertension
Aortic valve disease (stenosis and insufficiency)
Mitral insufficiency
 NB: There is an increase in size but function is compromised
 However, there is a LIMIT to the amount the tissue can
enlarge

19.  An adaptation to stress such as hypertrophy can progress to functionally
significant cell injury if the stress is not relieved.
 Whatever the cause of hypertrophy, a limit is reached beyond which the
enlargement of muscle mass can no longer compensate for the increased
burden.
 When this happens in the heart, several degenerative changes occur in the
myocardial fibers, of which the most important are fragmentation and loss of
myofibrillar contractile elements.
 Why hypertrophy progresses to these regressive changes is incompletely
understood. There may be finite limits on the abilities of the vasculature to
adequately supply the enlarged fibers, the mitochondria to supply ATP, or the
biosynthetic machinery to provide sufficient contractile proteins or other
cytoskeletal elements.
 The net result of these degenerative changes is ventricular dilation and
ultimately cardiac failure.

20. Hypertrophy
2. Compensatory hypertrophy may occur in an organ when the
contralateral organ is removed e.g.
Following nephrectomy on one side in a young patient, there
is compensatory hypertrophy as well as hyperplasia of the
nephrons of the other kidney
Adrenal hyperplasia following removal of one adrenal gland

21. HYPERPLASIA
 Hyperplasia is an increase in the number of parenchymal cells
resulting in enlargement of the organ or tissue
 Quite often, both hyperplasia and hypertrophy occur together
 Occurs due to a response from appropriate stimulus and ceases when
stimulus is removed
 An increase in NUMBER of cells
 Restricted to cells capable of mitosis
 epidermis, intestinal epithelium, and glandular tissue
 Physiological hyperplasia
 uterus and breast enlarge in pregnancy

22. Causes Of Hyperplasia
 A. Physiologic hyperplasia. The two most common types are as
follows:
1. Hormonal hyperplasia i.e. hyperplasia occurring under the
influence of hormonal stimulation e.g.
 Hyperplasia of female breast at puberty, during pregnancy and
lactation
 Hyperplasia of pregnant uterus
 Proliferative activity of normal endometrium after a normal
menstrual cycle
 Prostatic hyperplasia in old age

23. Causes Of Hyperplasia
2. Compensatory hyperplasia i.e. hyperplasia occurring following
removal of part of an organ or a contralateral organ in paired organ e.g.
 Regeneration of the liver following partial hepatectomy
 Regeneration of epidermis after skin abrasion
 Following nephrectomy on one side, there is hyperplasia of
nephrons of the other kidney.

24. Causes Of Hyperplasia
B. Pathologic hyperplasia: Most examples of pathologic hyperplasia are
due to excessive stimulation of hormones or growth factors e.g.
Endometrial hyperplasia following estrogen excess
In wound healing, there is formation of granulation tissue due to
proliferation of fibroblasts and endothelial cells
Formation of skin warts from hyperplasia of epidermis due to
human papilloma virus
Pseudocarcinomatous hyperplasia of the skin
Intraductal epithelial hyperplasia in the breast in fibrocystic
breast disease.
prostatic hypertrophy (BPH or thyroid enlargement

25.  Nevertheless,in many cases, pathologic hyperplasia constitutes a fertile soil in
which cancers may eventually arise.
 For example, patients with hyperplasia of the endometrium are at increased
risk of developing endometrial cancer

26. METAPLASIA
 Metaplasia is a change in which one adult cell type (epithelial or mesenchymal) is
replaced by another adult cell type.
 In this type of cellular adaptation, a cell type sensitive to a particular stress is replaced by
another cell type better able to withstand the adverse environment.
 Metaplasia is thought to arise by the reprogramming of stem cells to differentiate along a new
pathway rather than a phenotypic change (transdifferentiation) of already differentiated cells
 Epithelial metaplasia is exemplified by the change that occurs in the respiratory epithelium of
habitual cigarette smokers, in whom the normal ciliated columnar epithelial cells of the trachea
and bronchi often are replaced by stratified squamous epithelial cells
 The rugged stratified squamous epithelium may be able to survive the noxious chemicals in
cigarette smoke that the more fragile specialized epithelium would not tolerate.
 Metaplasia: change in phenotype of differentiated cells, often in response to chronic irritation,
that makes cells better able to withstand the stress; usually induced by altered differentiation
pathway of tissue stem cells; may result in reduced functions or increased propensity/tendancy
for malignant transformation

27.  Although the metaplastic squamous epithelium has survival advantages,
important protective mechanisms are lost, such as mucus secretion and ciliary
clearance of particulate matter.
 Because vitamin A is essential for normal epithelial differentiation, its deficiency
also may induce squamous metaplasia in the respiratory epithelium.
 Metaplasia need not always occur in the direction of columnar to squamous
epithelium; in chronic gastric reflux, the normal stratified squamous epithelium
of the lower esophagus may undergo metaplastic transformation to gastric or
intestinal-type columnar epithelium.
 Metaplasia also may occur in mesenchymal cells, but in these situations it is
generally a reaction to some pathologic alteration and not an adaptive response
to stress. For example, bone is occasionally formed in soft tissues, particularly
in foci of injury.
 The influences that induce metaplastic change in an epithelium, if
persistent, may predispose to malignant transformation.

28.  In fact, squamous metaplasia of the respiratory epithelium often coexists with
lung cancers composed of malignant squamous cells.
 It is thought that cigarette smoking initially causes squamous metaplasia, and
cancers arise later in some of these altered foci

29. DYSPLASIA
 Dysplasia means ‘disordered cellular development’, often
accompanied with metaplasia and hyperplasia; it is therefore also
referred to as atypical hyperplasia
 Dysplasia occurs most often in epithelial cells
 Epithelial dysplasia is characterized by:
cellular proliferation
cytologic changes.
 Dysplastic changes often occur due to:
chronic irritation
prolonged inflammation

30. DYSPLASIA
 On removal of the inciting stimulus, the changes may disappear
 In a proportion of cases, however, dysplasia progresses into:
 carcinoma in situ (cancer confined to layers superficial to
basement membrane)
or
invasive cancer
 The Dysplasia Changes include:
Increased number of layers of epithelial cells
Disorderly arrangement of cells from basal layer to the
surface layer

31. DYSPLASIA
Loss of basal polarity i.e. nuclei lying away from basement
membrane
Cellular and nuclear pleomorphism
Increased nucleocytoplasmic ratio
Nuclear hyperchromatism
Increased mitotic activity

33. Differences between Metaplasia and Dysplasia
Metaplasia
 Change of one type of epithelial
or mesenchymalcell to another
type of adult epithelial or
mesenchymal cell
 Epithelial (squamous, columnar)
and mesenchymal (osseous,
cartilaginous)
 Most commonly affects bronchial
mucosa, uterine endocervix;
others mesenchymal tissues
(cartilage, arteries)
Dysplasia
 Disordered cellular development,
may beaccompanied with
hyperplasia or metaplasia
 Epithelial only
 Uterine cervix, bronchial mucosa

34. Differences between Metaplasia and Dysplasia
Metaplasia
 Mature cellular
development
 Reversible on withdrawal of
stimulus
Dysplasia
 Disordered cellular development
(pleomorphism,nuclear
hyperchromasia, mitosis, loss of
polarity)
 May regress on removal of inciting
stimulus, or may progress to higher
grades of dysplasia or carcinoma in
situ

35. Anaplasia
 Cells differentiate to a more IMMATURE or embryonic form.
 Malignant tumors are characterized by anaplastic cell growth.

36. Summary: Cellular Changes