physiological and pathological adaptations

1. Adaptations of Cellular Growth
and Diffrentiation

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 : Endometrial hyperplasia.
3. Compensatory hypertrophy : Woman with a unicornuate uterus
who successfully carries a pregnancy to term. Enlargement of a
remaining kidney after the other has been removed.

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.
（ 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 proteins of fetal & neonatal
forms
• Selective hypertrophy : hypertrophy of SER of
hepatocytes in patients treated with barbiturates

12. Hyperplasia
 Definition : increase in number of cells in an organ
or tissue, 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.

13. 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.
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

14. Physiological hyperplasia

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

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. 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

24. 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

25. Denervation atrophy
atrophic skeletal muscle fibres

26. 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

27. 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.

28. DISUSE ATROPHY
(Poliomyelitis)

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

30. Mechanism of atrophy
• Reduction in structural components
• Decreased number of mito, myofilaments, ER via
proteolysis (lysosomal proteases;
ubiquitinproteosome 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.

32.  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.

33. 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

34. 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.

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

36. Squamous metaplasia in bronchitis

37. METAPLASIA-ESOPHAGUS

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

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Note that the columnar ciliated epithelium has been
replaced by squamous epithelium.

40. 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.

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

42. Mechanism 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.

43.  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.

44. 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.

45. AGEING

46.  Cellular aging is the result of a progressive decline in the
life span and functional activity of cells.
 Several abnormalities contribute to the aging of cells
 Accumulation of mutations in DNA.
 Decreased cellular replication.
 Defective protein homeostasis
 Persistent inflammation