1. Cellular Injury and Responses to stress
Faculty of Medicine
Department of Pathology
Hussam Telfah, MBBS, FRCPath

2. Cellular Response to Stress
Normal cell needs special conditions “environment” to function properly. Homeo-stasis : similar-standing still. Range of Temperature, PH, Glucose etc

3. Cellular Responses
Adaptation: hypertrophy, hyperplasia, atrophy, metaplasia.
Injury: reversible and irreversible.
Intracellular accumulation; calcification
Cellular aging.

4. 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.

5. Hypertrophy
Hypertrophy is an increase in cell size resulting in an increase in the size of the organ.
Alone in nondividing cells or coexisting with hyperplasia in dividing cells.
Physiologic vs pathologic.
Increased functional demand (workload) or stimulation by hormones or growth factors.

6. Hypertrophy
Muscle

7. Hypertrophy
Heart: left ventricle hypertrophy.

8. Hypertrophy
Uterus

9. Hypertrophy
There is a limit for hypertrophy beyond which the muscle is no longer able to compensate for the increased burden.
Some times subcellular organelle may undergo selective hypertrophy.
Example: drugs lead to hypertrophy of smooth endoplasmic reticulum only.

10. Hyperplasia
Increased number of cells resulting in increase of the size of the organ or tissue.
Takes place in cells capable of dividing.
Physiologic vs pathologic.

11. Hyperplasia
Physiological Hyperplasia (hormonal or compensatory), Examples:
Uterine enlargement during pregnancy
Female breast in puberty & lactation
Compensatory hyperplasia in the liver
Pathological
Hyperplasia of the endometrium (excessive hormone stimulation).
Wound healing (Effects of growth factors).
Infection by papillomavirus
Hyperplasia can be a fertile soil for development of neoplasia

12. Hyperplasia
Prostate

13. Hyperplasia
Endometrium

14. Atrophy
Reduced size of an organ or tissue as a result from a decrease in cell size and number.
Physiologic :
Embryonic development.
Pathologic:
Decreased workload (Disuse atrophy)
Loss of innervation (Denervation atrophy)
Diminished blood supply.
Inadequate nutrition.
Loss of endocrine stimulation.
Pressure.

15. Metaplasia
Metaplasia is a “reversible” change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type.
New epithelium is better in dealing with the current stress or irritation.
Persistence of factors causing metaplasia may lead to progression into malignant transformation.
Examples: respiratory , GIT, cervix, muscle.

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

17. Causes of Cell Injury Oxygen Deprivation: hypoxia and ischemia
Chemical agents & Drugs.
Physical agents: mechanical trauma, changing T⁰.
Infection Agents: viruses to worms.
Immunological reactions: autoimmune.
Genetic derangement: chromosomal to single amino acid defect
Nutritional Imbalances: Deficiency vs excess.

18. Morphologic alterations in cell injury Reversible injury
Generalized swelling of the cell: failure of energy-dependent ion pumps in the plasma membrane result in disturbances in ionic and fluid homeostasis. It is usually the first manifestatioin. Another names hydropic change or vacuolar degeneration.
Plasma membrane alterations: blebs, blunting or loss of villi and loosening of intercellular attachments.

19. Morphologic alterations in cell injury Reversible injury
Mitochondrial changes: swelling and appearance of small amorphus densities.
Dilatation of ER and detachment of polysomes (ribosomes) with possibility of myelin figure formation.
Nuclear alterations: nuclear chromatin clumping.

20. Kidney tubules
Downloaded from: StudentConsult (on 24 September :38 PM)
© 2005 Elsevier

21. Figure 1-8 Schematic illustration of the morphologic changes in cell injury culminating in necrosis or apoptosis.
Downloaded from: StudentConsult (on 24 September :56 PM)
© 2005 Elsevier

22. Morphologic alterations in cell injury irreversible injury (Necrosis)
Result from denaturation of intracellular proteins and enzymatic digestion of cells.
Loss of membrane integrity.
Digestion enzymes: lysosomes of dying cells and leukocytes.

23. Morphologic alterations in cell injury irreversible injury (Necrosis)
Increased eosinophilia in H&E stain.
Vacuolation due to digestion of cytoplasmic organelles.
Myelin figures: aggregates of damaged cell membranes (phospholipids). Then they are either phagocytosed by other cells or further degraded into fatty acids and calcify.
Plasma and organelle membrane discontinuities.

24. Morphologic alterations in cell injury irreversible injury (Necrosis)
Marked dilatation of mitochondria and appearance of large densities.
Nuclear changes: breakdown of DNA
- Karyolysis: loss of DNA, fade of basophilia.
- Pyknosis: nuclear shrinkage and increased
basophilia.
- Karyorhexis: fragmentation of the pyknotic
nucleus.
- Disappearance of the nucleus.

26. Patterns of tissue necrosis
Coagulative necrosis: preservation of the architecture of dead tissue for at least some days.
Denaturation of structural proteins and enzymes.
Eosiniphilic anucleated cells
Cells are removed by inflammatory leukocytes.

27. Patterns of tissue necrosis
Ischemia in any organ except the brain may lead to coagulative necrosis.
Infarction: localised area of coagulative necrosis.

29. Patterns of tissue necrosis
Liquifactive necrosis: digestion of the dead cells resulting into a liquid jelly-like mass.
In focal bacterial or fungal infections and in hypoxic death in central nervous system.
Creamy yellow due to accumulation of dead leukocytes (pus).