1. Cellular Injury, death and Responses to stress
Faculty of Medicine
Department of Pathology
Manar hajeer, MD

2. Cells are active participants in their environment, constantly adjusting their structure and function to accommodate changing demands and extracellular stresses.
Cells tend to maintain their intracellular milieu within a fairly narrow range of physiologic parameters; that is, they maintain normal homeostasis.

3. As cells encounter physiologic stresses or pathologic stimuli, they can undergo adaptation, achieving a new steady state.
If the adaptive capability is exceeded or if the external stress is harmful, cell injury develops .
Within certain limits injury is reversible, and cells return to a stable baseline; however, severe or persistent stress results in irreversible injury and death

6. Objectives: Adaptive mechanisms to stresses. Causes of cell injury.
Reversible and irreversible cell injury.
Patterns of cell death (apoptosis and necrosis).

7. Cellular Adaptation principal adaptive responses: Hypertrophy.
Hyperplasia.
Atrophy.
Metaplasia.

8. Cellular Adaptations
Reversible changes in size, number, phenotype, metabolic activity or function in response to changes in environment.
Adaptation can be both physiologic and pathologic.

9. 1-Hypertrophy
Hypertrophy is an increase in cell size resulting in an increase in the size of the organ.
Pure in nondividing cells or coexisting with hyperplasia in dividing cells.
Increased amount of structural proteins and organelle.
Physiologic vs pathologic.
Increased functional demand (workload) or stimulation by hormones or growth factors.

10. Hypertrophy
Heart: left ventricle hypertrophy(pathologic).

11. Hypertrophy
In skeletal and cardiac muscles (pure hypertrophy)

12. Hypertrophy
Uterus smooth muscles in pregnancy (hypertrophy and hyperplasia) (physiologic)

13. Hypertrophy
There is a limit for hypertrophy, beyond which the muscle is no longer able to compensate for the increased burden.

14. 2-Hyperplasia
Increased number of cells resulting in increased mass of the organ or tissue.
Takes place in cells capable of dividing.
Physiologic vs pathologic.

15. Hyperplasia Physiological hyperplasia Examples:
Uterine enlargement during pregnancy
Female breast in puberty & lactation

16. Pathological hyperplasia
Hyperplasia of the endometrium (excessive hormone stimulation).
Nodular prostatic hyperplasia
Infection by papillomavirus (HPV)
Pathologic hyperplasia can be a fertile soil for development of neoplasia

17. Hyperplasia of prostate Nodular prostatic hyperplasia

18. Endometrial Hyperplasia
Endometrium

19. 3-Atrophy
Reduced size of an organ or tissue as a result from a decrease in cell size .
Physiologic :
-Embryonic development.
-Gravid uterus involution.
-Hormonal withdrawal after menopause.
Pathologic:
-Decreased workload (Disuse atrophy)
-Loss of innervation (Denervation atrophy)
-Diminished blood supply.
-Inadequate nutrition.
-Loss of endocrine stimulation.
-Aging (senile atrophy)

21. 4-Metaplasia
Metaplasia is a “reversible” change in which one differentiated cell type is replaced by another cell type.
New cell type is better in dealing with the current stress or irritation.
Persistence of factors causing metaplasia may lead to progression into malignant transformation.
Examples: respiratory and esophagus.

22. Metaplasia
Replacement of ciliated columnar epithelium with stratified squamous epithelium in the respiratory tract of a smoker.

24. chronic gastric reflux, the normal stratified squamous epithelium of the lower esophagus may undergo metaplastic transformation to gastric or intestinal-type columnar

25. Causes of Cell Injury Oxygen Deprivation: hypoxia and ischemia
Chemical agents & Drugs.
Physical agents: trauma, changing tempreture, radiation, chemicals.
Infectious Agents: viruses to worms.
Immunological reactions.
Nutritional Imbalances: Deficiency vs excess.
Aging.

26. Cell injury
All stresses and noxious influences exert their effects first at the molecular or biochemical level.
Cellular function may be lost long before cell death occurs.
The morphologic changes of cell injury (or death) occur very late.

28. 1-Reversible Injury
cellular swelling .
and
fatty change.

29. Cellular swelling is the result of failure of energy-dependent ion pumps in the plasma membrane, leading to an inability to maintain ionic and fluid homeostasis.
Fatty change

30. Apoptosis
Pathway of cell death induced by a tightly regulated suicide program in which cells activate enzymes capable of degrading the cells' own nuclear DNA and nuclear and cytoplasmic proteins.

31. The plasma membrane of the apoptotic cell remains intact.
Apoptotic bodies (contain portions of the cytoplasm and nucleus) become targets for phagocytosis before their contents leak out and so there would be no inflammatory reaction.

32. Causes of Apoptosis Physiologic situations:
To eliminate cells that are no longer needed OR to maintain a steady number of various cell populations in tissues.

33. Physiologic apoptosis
Embryogenesis.
involution of hormone-dependent tissues upon hormone withdrawal. (endometrium and breast after pregnancy)
Cell loss in proliferating cell populations. (GIT)
Death of host cells after serving their useful function. (neutrophils and lymphocytes in inflammation)
Elimination of potentially harmful self-reactive lymphocytes.
Cell death induced by cytotoxic T lymphocytes (tumor cells and viraly infected cells)

34. Pathologic situations
No inflammatory host reaction.
Examples:
DNA damaged cells,.
Cells with accumulation of misfolded proteins,
Certain infections (viral ones): may be induced by the virus (as in human immunodeficiency virus infections) or by the host immune response (as in viral hepatitis).
Pathologic atrophy in parenchymal organs after duct obstruction (pancreas, parotid and kidney)

35. Feature Necrosis Apoptosis Cell size Enlarged (swelling)
Enlarged (swelling)
Reduced (shrinkage)
Nucleus
Pyknosis → karyorrhexis → karyolysis
Fragmentation into nucleosome-size fragments
Plasma membrane
Disrupted
Intact; altered structure, especially orientation of lipids
Cellular content
Enzymatic digestion; may leak out of cell
Adjacent inflammation
Frequent No
Physiologic or pathologic role
Invariably pathologic (culmination of irreversible cell injury)
Often physiologic, means of eliminating unwanted cells; may be pathologic after some forms of cell injury, especially DNA damage