basic pathogenesis of cell growth, differentiation, and adaptation

1. Adaptations of Cellular Growth
and Diffrentiation
Dr. Rajshree Singh

2. Cell Adaptation
• Definition : Reversible change in size, number,
phenotype, metabolic activity, or functions of cells in
response to change in their environment
• a state that lies intermediate between the normal,
unstressed cell and the injured, overstressed cell.
• Cells can adapt to acceptable changes in their
environment by modifying metabolism or growth
pattern

3. Environmental changes can be physiological or
pathological
• Physiologic Adaptation : In response to normal
stimulation by hormones or endogenous chemical
substances
• Pathologic Adaptation : provide the cells with the
ability to survive in their environment and perhaps
escape injury

4. Forms of Cellular Adaptation
SIZE & NUMBER:
• Atrophy
• Hypertrophy
• Hyperplasia
DIFFERENTIATION OF CELLS:
• Metaplasia
• Dysplasia

5. Hypertrophy
• Definition :
– Increase in the size of cells, resulting in an
increase in the size of the organ
– Can be physiologic & pathologic
• No new cells, just larger cells
• Due to increase functional demand or by stimulation
of hormones & growth factors

6. Examples of Hypertrophy
1. Increase workload :
• Physiologic : Skeletal muscle hypertrophy in
response to exercise
• Pathologic :Myocardium in hypertensive heart
disease due to stimulus is chronic hemodynamic
overload
2. Hormone induced :
• Physiologic : uterus during pregnancy stimulated
by estrogenic hormones
• Pathologic :
3. Compensatory hypertrophy

7. 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,
Normal uterus gravid uterus
（From ROBBINS BASIC PATHOLOGY，2003）

8. Physiological hypertrophy
Skeletal muscle hypertrophy in response to exercise

9. Left : Normal heart
Center : Hypertrophied heart
Right : Hypertrophied and dilated heart

10. Mechanism of hypertrophy
• Due to increase production of cellular proteins
• By the actions of
– Growth factors : TGF-β, IGF-1, FGF
– Vasoactive agents : α-adrenergics, angiotensin –II
– Undergo 2 common pathways : PI3K/Akt pathway
& G-protein coupled receptors
• Expression of contractile proeins of fetal & neonatal
forms
• Selective hypertrophy : hypertrophy of SER of
hepatocytes in patients treated with barbiturates

11. Hyperplasia
• Definition : increase in number of ells in an organ or
issue, usually resulting in increased mass of organ or
tissue
• Hyperplasia is also an important response of
connective tissue cells in wound healing, in which
proliferating fibroblasts and blood vessels aid in
repair.

12. Types of hyperplasia
1.Physiologic: Response to need, e. g.
– hyperplasia of the female breast epithelium at
puberty or in pregnancy
– Hyperplasia uterus during pregnancy.

13. Physiological hyperplasia
Endometrium in the menstrual cycle

14. 2. Compensatory: Response to deficiency, e. g.
– Hyperplasia following surgical removal of part of
liver or of one kidney
– hyperplasia of the bone marrow in anemia
– regeneration of liver following partial
hepatectomy

15. 3. Excessive stimulation: Pathologic:
Hormonal :
– as in ovarian tumor producing estrogen and
stimulating endometrial hyperplasia
– androgen mediated enlargement of prostate in
benign prostatic hyperplasia
Other chemicals
– pancreatic islet hyperplasia in infants of a diabetic
mother (stimulated by high glucose level)

17. Nodular hyperplasia of prostate
From a young man
showing uniform
texture of gland
From an elderly man
showing irregular
hyperplastic nodules.
This would cause
obstruction

18. Microscopic view of prostatic hyperplasia

19. 4. Viral infection : pathologic
– papilloma viruses
5. Failure of regulation: Pathologic,
– Hyperplasia of thyroid in Grave’s disease
– hyperparathyroidism resulting from renal failure
or vitamin D deficiency.
6. Neoplastic: Total loss of normal control mechanism.
Should not be termed hyperplasia

20. Thyroid hyperplasia

21. Mechanism of hyperplasia
• Result of
– Growth factor driven proliferation of mature cells
– In some cases, increase output of new cells from
tissue stem cells

22. Relationship between hyperplasia & hypertrophy
• These may occur independently or together.
• Often triggered by same stimulus
• Reflected by an increase in size and weight of an
organ
• Cells capable of dividing : undergo both Hypertrophy
& hyperplasia
• Non-dividing cells : undergo hypertrophy (myocardial
fibres)
• Examples : gravid uterus during pregnancy

23. Hypertrophy & hyperplasia
Normal uterus
Pregnant uterus

24. Atrophy
• Definition : reduced size of an organ or tissue resulting
from a decrease in cell size & number
• Types
A. Physiologic atrophy :
• Embryonic structures during Fetal development :
thryoglossal duct, notochord
• Involution :
– Uterus shortly after parturition
– breast after cessation of lactation

25. B. Pathologic Atrophy
1. Diminished blood supply:
– Ischemic atrophy
– Due to arterial occlusive disease leading to
atrophy of brain in patients with cerebrovascular
diseases
2. Loss of nerve stimulus:
– Denervation atrophy
– Atrophy of muscle fibers due to damage to
nerves

26. Denervation atrophy
A= atrophic skeletal muscle fibres

27. 3. Loss of endocrine stimulation:
– In hormone responsive tissues such as breast &&
reproductive organs
– Physiologic Atrophy of endometrium, vaginal
epithelium & breast due to loss of estrogen
stimulation after menopause
4. Inadequate nutrition
– Muscle wasting in protein-energy malnutrition
(marasmus)
– Cachexia in patients with chronic inflammatory
diseases & cancer

28. 5. Pressure atrophy:
– Long time tissue compression which results in
compromised blood supply by pressure exterted
by expanding mass
– Atrophy of surrounding tissue by benign tumor
6. Decreased workload :
– Disuse atrophy
– Skeletal muscle atrophy in fractured bone
immobilized by cast

29. DISUSE ATROPHY
(Poliomyelitis)

30. 7. Aging:
– Senile atrophy
– Decrease in body fat, muscle mass, brain size
seen with aging

31. CORTICAL ATROPHY

32. Mechanism of atrophy
• Reduction in structural components
• Decreased number of mito, myofilaments, ER via
proteolysis (lysosomal proteases; ubiquitin-
proteosome system)
• Increase in number of autophagic vacuoles
• Debris in autophaic vacuoles may resist digestion 
Residual bodies (i.e. lipofuscin)  brown atrophy
• NB: diminished function but not dead
• Cell loss is commonly replaced by either adipose
tissue or fibrous tissue

34. Other causes of a small organ other than
atrophy
• Hypoplasia: incomplete growth of an organ
• Agenesis: complete failure of development of
an organ in embryogenesis

35. Metaplasia
• Definition : reversible change in which one
diffrentiated cell type (epithelial or mesenchymal) is
replaced by another cell type
• Causes:
1. Changes in environment
2. Irritation or inflammation
3. Nutritional
4. Tissue injury

36. Types of metaplasia
1. Columnar to squamous (Squamous metaplasia)
– In respiratory tract in response to chronic
irritation (cigarette smokers) normal ciliated
columnar epithelium of trachea replaced by
stratified squamous epithelium
– Squamous metaplasia of resp. epithelium by
vitamin A deficiency
– Stones in excretory ducts of salivary gland,
pancreas, or bile duct lead to change from
columnar epithelium to stratified squamous
epithelium

37. Schematic diagram of columnar to squamous metaplasia
（From ROBBINS BASIC PATHOLOGY，2003）

38. Squamous metaplasia in bronchitis

39. METAPLASIA-ESOPHAGUS

40. 3. Squamous to columnar metaplasia
• Barrett’s esophagus : esophageal squamous
epithelium replaced by intestinal-like columnar
cells due to refluxed gastric acid

41. Photomicrograph of the trachea from a
smoker. Note that the columnar ciliated
epithelium has been replaced by squamous
epithelium.

42. 4. Connective tissue metaplasia
• Formation of bone, cartilage or adipose
(mesenchymal tissue) in tissues that normally do
not contain these elements
• Myositis ossificans : bone formation in muscle
ocassionally occuring after intramuscular
hemorrhage
5. transitional epithelium to squamous
– Urothelium in response to stone

43. Photomicrograph of the junction of normal
epithelium (1) with hyperplastic transitional
epithelium (2).

44. Mehcanism of metaplasia
• Reprogramming
1. of stem cells present in normal tissues
2. of undifferentiated mesenchymal cells
in connective tissue
• Mediated by signals from cytokines, GF or ECM
• Leading to induction of specific transcription factors

45. • Epithelial metaplasia is a two-edged sword and, in
most circumstances, represents an undesirable
change.
• Moreover, the influences that predispose to such
metaplasia, if persistent, may induce cancer
transformation in metaplastic epithelium.

46. Summary
• Cells adapt to altered environment
• Metabolic adaptation
• Cell stress response
• Changes in growth pattern
– Hyperplasia, hypertrophy, atrophy,
involution, metaplasia
• Growth factors, controlling proliferation
or cell death, play a key role in cell
adaptations in disease

47. ANY QUESTIONS ??