1. In the name of ALLAH ……….

2. Adaptation of Cellular Growth and Differentiation
Cell Injury-1
Adaptation of Cellular Growth and Differentiation
Dr. Shoaib Raza
Associate Professor, Pathology, RIHS

3. The objectives of this lecture are:
Introduce the term adaptation and cell injury
Define and brief explanation of various forms of adaptation; like
Hypertrophy
Hyperplasia
Atrophy
Metaplasia

4. Cell injury
When the adaptive capabilities of the cell are exceeded, the cell injury ensues
Reversible cell injury
Irreversible cell injury
Cell death, necrosis or apoptosis
Causes of cell injury:
Ischemia
Chemical agent
Physical agent
Nutritional imbalance
Immunologic mechanism
Biological agent
Genetic derangements
Aging

6. Adaptation
Adaptations are reversible change in the SIZE, NUMBER, PHENOTYPE, METABOLIC ACTIVITY or FUNCTIONS of the cells in response to changes in their environment.
Such adaptations may take several forms:
Hypertrophy
Hyperplasia
Atrophy
Metaplasia

7. Hypertrophy
Increase in the size of cell resulting in an increase in the size of organ.
Seen in non-dividing cells
Pathologic hypertrophy
Physiologic hypertrophy
Causes may include:
Increased functional demand
Stimulation by hormone
Stimulation by growth factors
Increased work load

8. Causes and examples of hypertrophy
Physiologic example
Pathologic example
Increased work load
Skeletal muscle hypertrophy in athletes and body builders
Myocardial hypertrophy, due to hypertension or out flow obstruction
Stimulation by hormone
Uterus during pregnancy
Prostatic enlargement in old males
Stimulation by growth factors

10. Mechanism of Hypertrophy
Result of increased production of cellular proteins
Increased actions of mechanical sensors triggered by increased work load
Growth factors (TGF-β, IGF-1, FGF, etc.)
Vasoactive agents (Endothelin-1, Angiotensin-II)
These stimuli work coordinately to increase the synthesis of muscle protein, responsible for hypertrophy

11. Mechanism of Hypertrophy (continue)
Switch of contractile proteins from adult to fetal form
α-isoform of heavy chain of myosin is replaced by β-isoform
Reinduction of ANF
May be a combination of mechanical and chemical stimuli, leads to genetic and molecular rearrangements during hypertrophy

12. Subcellular alterations
Sometimes a subcellular organelle may undergo hypertrophy
Endoplasmic reticulum of hepatocytes in barbiturates poisoning
Mitochondrial hypertrophy (giant mitochondria)

14. Examples of hypertrophy
Physiologic Hypertrophy
Pathologic Hypertrophy
Breasts at puberty
Breasts during pregnancy
Uterus during pregnancy
Skeletal muscle hypertrophy in athletes
Myocardial hypertrophy
Prolonged hypertension

15. Hyperplasia
An increase in the number of cells in an organ or tissue, usually resulting in increased mass of the organ or tissue.
Seen in the cells which are capable of dividing, and thus increasing the number of cells
Usually accompanied by hypertrophy as well
May be
Physiologic OR
Pathologic

16. Physiologic Hyperplasia
Can be divided into:
Hormonal hyperplasia:
Proliferation of glandular epithelium of female breast at puberty and during pregnancy
Compensatory hyperplasia:
Live liver donors

17. Pathologic Hyperplasia
Mostly caused by excessive hormone or growth factors acting on target cells
Endometrial hyperplasia
Benign prostatic hyperplasia
May be a characteristic response to certain viral infections. e.g. Human Papilloma Virus

19. Mechanism of Hyperplasia
Is the result of growth factor-driven proliferation of mature cells
Or in some cases, increased output of new cells from tissue stem cells
After some minor hepatic injury, liver cells regenerate, under influence of certain growth factors
But if regenerative capacity of hepatocyte is compromised (e.g. in hepatitis), hepatocyte can instead regenerate from intrahepatic stem cells

20. Normal endometrium (Proliferative phase)
Endometrial Hyperplasia

21. Examples of hyperplasia
Physiologic
Pathologic
Hyperplasia of breasts at puberty
Hyperplasia of breasts during pregnancy
Hyperplasia of endometrium during proliferative phase of menstrual cycle
Hyperplasia of bone marrow
Endometrial hyperplasia
Prostatic hyperplasia
Hyperplastic polyps in GIT
Hyperplasia of thyroid gland in Grave’s disease
Stratified squamous hyperplasia of skin and mucus membranes in HPV infection

22. Consequences of hyperplasia
Increased cell number results in:
Increased functional capacity
Increase in the size of organ/tissue
Increased demand of nutrition and perfusion
In some cases hyperplasia presents a fertile soil for the development of cancer (neoplasia)

23. Atrophy
Reduction in the size of cell associated with reduction in the size of tissue or organ
Can be
Physiologic:
During embryogenesis and metamorphosis
Uterus after parturition
Pathologic

24. Causes of Atrophy Pathologic atrophy:
Decreased work load (Disuse atrophy)
Loss of innervation (Denervation atrophy)
Diminished blood supply (Ischemic atrophy0
Inadequate nutrition (Marasmus, cachexia)
Loss of endocrine stimulation
Pressure
Physiologic atrophy:
Senile atrophy
Hormonal atrophy in breasts or uterus

25. Mechanism of atrophy Decreased protein synthesis
Increased protein degradation
Increased autophagy (self eating)
Increased number of autophagic vacuoles (brown atrophy)

30. metaplasia
One adult (differentiated) cell type is replaced by another cell type
Usually reversible
Almost always pathological
Columnar to squamous cell (chronic bronchitis)
Squamous to columnar (Barrett’s esophagus)
May be preneoplastic condition

35. Any questions