1. Pathologic hyperplasia constitutes a fertile soil in which cancerous proliferations may eventually arise. Patients with hyperplasia are at increased risk for developing cancer. 2. Hyperplasia is the result of growth factor-driven proliferation of mature cells and increased output of new cells from tissue stem cells. 3. Metaplasia is a reversible change where one cell type replaces another. It results from the reprogramming of stem cells or undifferentiated mesenchymal cells, causing them to differentiate along a new pathway in response to environmental signals.

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2. Adaptations of Cellular
Growth& Differentiation
BY
DR ABDUL AZIZ SHAIKH
MBBS,M.PHIL(HISTOPATHOLOGY)
ASSISTANT PROFESSOR

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4. Pathologic Hyperplasia
Although these forms of pathologic
hyperplasia are abnormal, the process
remains controlled and the hyperplasia
regresses if the hormonal stimulation
is eliminated Thus, while hyperplasia is
distinct from cancer,

5. Pathologic Hyperplasia
pathologic hyperplasia constitutes a
fertile soil in which cancerous
proliferations may eventually arise.
For instance, patients with hyperplasia
of the endometrium are at increased
risk for developing endometrial cancer

6. Pathologic Hyperplasia
 Hyperplasia is a characteristic response to
certain viral infections, such as papilloma
viruses, which cause skin warts and several
mucosal lesions composed of masses of
 hyperplastic epithelium.

7. Mechanisms of Hyperplasia
Hyperplasia is the result of growth
factor-driven proliferation of
mature cells and, in some cases,
by increased output of new cells
from tissue stem cells.

8. Mechanisms of Hyperplasia
 For instance, after partial hepatectomy
growth factors are produced in the liver that
engage receptors on the surviving cells and
activate signaling pathways that stimulate cell
proliferation.

9. Atrophy
Atrophy is defined as a
reduction in the size of an organ
or tissue due to a decrease in
cell size and number.Atrophy can
be physiologic or pathologic.

10. Atrophy
 Physiologic atrophy is common during normal development.
Some embryonic structures, such as the notochord and thyro
glossal duct, undergo atrophy during fetal development.
Decrease in the size of the uterus that occurs shortly after
parturition is another form of physiologic atrophy.

11. Pathologic atrophy
 Local or generalized.
 causes of atrophy
 Decreased workload (atrophy of disuse):
 Fractured bone is immobilized in a plaster cast
 Complete bed rest, skeletal muscle atrophy
 Initial decrease in cell size is reversible

12. Loss of innervation (denervation atrophy)
The normal metabolism and function of skeletal
muscle are dependent on its nerve supply
. Damage to the nerves leads to atrophy of the
muscle fibers supplied by those nerves

13. Diminished blood supply
A gradual decrease in blood supply (ischemia) to a tissue
as a result of slowly developing arterial occlusive
disease results in atrophy of the tissue.
In late adult life, the brain may undergo progressive
atrophy, mainly because of reduced blood supply as a
result of atherosclerosis . This is called senile atrophy,
which also affects the heart.

14. Inadequate nutrition
Profound protein-calorie malnutrition(marasmus) is
associated with the utilization of skeletal muscle proteins
as a source of energy after other reserves such as adipose
stores have been depleted.
Cachexia (marked muscle wasting)

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17. Pressure atrophy
Tissue compression for any
length of time can cause
atrophy.
In atrophic muscle, the cells contain
fewer mitochondria and myofilaments and
a reduced amount of rough endoplasmic
reticulum (RER).

18. Loss of endocrine stimulation.
 The loss of estrogen stimulation
 after menopause results in physiologic
atrophy of the endometrium, vaginal
epithelium, and breast
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20. Metaplasia
Metaplasia is a reversible change
in which one differentiated cell
type (epithelial or mesenchymal)is
replaced by another cell type.
The most common epithelial
metaplasia is columnar to squamous

21. Metaplasia
Stones in the excretory ducts of the
salivary glands, pancreas, or bile
ducts, which are normally lined by
secretory columnar epithelium, may
also lead to squamous metaplasia
by stratified squamous epithelium.

23. Metaplasia
Moreover, the influences that predispose to
metaplasia, if persistent, can initiate
malignant transformation in metaplastic
epithelium.
Thus, a common form of cancer in the
respiratory tract is composed of squamous
cells, which can arise in areas where the
normal columnar epithelium has been
replaced by squamous epithelium

24. Metaplasia
Connective tissue metaplasia is the 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,occasionally occurs after
intramuscular hemorrhage.

25. Mechanisms of Metaplasia
Metaplasia does not result from a
change in the phenotype of an already
differentiated cell type; instead it is the
result of a reprogramming of stem cells
that are known to exist in normal
tissues, or of undifferentiated
mesenchymal cells present in
connective tissue

27. Mechanisms of Metaplasia
Metaplasia does not result from a change in
the phenotype of an already differentiated
cell type;
instead it is the result of a reprogramming of
stem cells that are known to exist in normal
tissues, or of undifferentiated mesenchymal
cells present in connective tissue.

28. Mechanisms of Metaplasia
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.

29. Mechanisms of Metaplasia
These external stimuli promote
the expression of genes that
drive cells toward a specific
differentiation pathway

30. A 30-year-old man sustains a left femoral fracture ,
and his leg is placed in a plaster cast. After the leg has
been immobilized for several weeks, the diameter of
the left calf has decreased. This change is most likely
□ (A) Aplasia
□ (B) Hypoplasia
□ (C) Atrophy
□ (D) Dystrophy
 □ (E) Hyalinosis

31. ANS
(C) Atrophy

32. A 32-year-old man experiences “heartburn” and gastric reflux after
eating a large meal. After many months of symptoms, he
undergoes upper gastrointestinal endoscopy, and a biopsy
specimen of the esophageal epithelium is obtained. Which of the
following pathologic changes, has most likely occurred?
 (A) Squamous metaplasia
 □ (B) Mucosal hypertrophy
 □ (C) Columnar epithelial metaplasia
 □ (D) Atrophy of lamina propria
 □ (E) Goblet cell hyperplasia

33. ANS
(C) Columnar
epithelial
metaplasia