CELL INJURY & ADAPTATION By: Miss S antoshi N aik Assistant Professor

1. CELL INJURY & ADAPTATION By: Miss Santoshi Naik Assistant Professor Yenepoya Pharmaceutical College and Research Centre

2. Cell injury: is the alteration of cell structure or biochemical functioning resulting from some stress that exceeds the ability of the cell to compensate through normal physiologic adaptive mechanisms. • Adaptation : is the capability of the cells under stress to adapt to the changes in the physiologic and pathologic conditions by alteration of their morphology, pattern of growth or metabolic activity.

3. Dose intensity Cell vulnerability Cell injury = Disease Cell stress Adaptation or Cell injury

4. CELL INJURY REVERSIBLE CELL INJURY IRREVERSIBLE CELL INJURY CELL DEATH

5. Dose intensity : is the intensity to which the cells are exposed to stress conditions. • Cell vulnerability: Some cells are inherently vulnerable to cell injury ie. They are fragile in nature and thus eventually die. • Reversible cell injury: In mild forms of injury the morphologic or the functional changes are reversible if the damaging stimulus is removed. • Irreversible cell injury: In severe forms of injury the cell cannot recover and it dies.

6. Cell death are of 2 types: • Cell necrosis: When there is any damage to cell membrane then the enzymes leak out of lysosomes and digest the cell resulting in cell death. The cellular contents also leak out through the damaged plasma membrane and elicit the host of reactions eg. Inflammation. • Apoptosis: When the cell is deprived of growth factors or the cell’s DNA or proteins are damaged, then the cell kills itself by other type of death called apoptosis.

8. Morphologic Adaptation to cell injury 1) Atrophy: • Atrophy is the shrinkage in cell size by loss of cellular substance. Thus in atrophy the cells will be smaller than normal. • Causes: Diminished blood supply or nutrition, aging of cells or decreased cellular components (autophagy). • Autophagy means the cells fuse with lysosomes and eventually the cell components are lysed by lysosomes.

10. 2) Hypertrophy: • Hypertrophy is the increase in cell size resulting from increased functional capacity & thus cells are bigger than normal. • 2 types of Hypertrophy: Physiologic hypertrophy and Pathologic hypertrophy. • Example of Physiologic hypertrophy: • Reproductive organs get bigger when there is demand like mammary glands after pregnancy. • Muscles get bigger after heavy exerscise. • Example of Pathologic hypertrophy: • If there is blockage of heart then the heart muscles face unnatural load leading to hypertrohy and then eventually heart failure.

12. 3) Hyperplasia: • Hyperplasia refers to increase in cell number in tissues. • This may eventually lead to neoplasia (cancer) • Example: Hyperplasia of female breast at puberty, pregnancy and lactation.

13. 4) Metaplasia: • Metaplasia refers to reversible change of one epithelial adult cell to another type in response to abnormal stimuli and reverts back to normal on removal of stimulus but if persists then leads to neoplasia. • Example: Urinary bladder is lined with transitional epithelium but in chronic infection it is replaced with squamous epithelium.

14. 5) Dysplasia: • Dysplasia refers to disordered cellular development. It is always accompanied with metaplasia and hyperplasia and thus also referred as atypical hyperplasia. • Example: 1) disorderly arrangement of cells 2) nuclei lying away from basement membrane.

15. Atrophy NORMAL CELL Hypertrophy Hyperplasia Dysplasia Metaplasia

16. CAUSES OF CELL INJURY

18. PATHOGENESIS OF CELL INJURY

19. PATHOGENESIS OF CELL INJURY • Mitochondrial damage • Mitochondrial integrity is cruicial for cell survival as it is the power house of the cell. Causes: • Increase Cytosolic calcium, free radicals Effects: • No ATP generation • Release of cytochrome into cytoplasm

21. 2) Cell membrane damage • Cell membrane controls the movement of substances in and out of the cell and protects the cell from its surroundings. • It consists of phospholipid molecules embedded with protein molecules. • Causes : • Direct damage by toxins (bacteria, viruses, physical or chemical injury) • Calcium- mediated phospholipase and protease activation. • Effects: • Loss of Membrane barriers thus loss of cellular contents. Eg. Loss of mitochondria which results in decreased ATP production. • Loss of cell integrity

23. 3) Ribosome damage Ribosomes are the protein (DNA & RNA) making factories of the cell • Causes : • Oxidative damage through Reactive oxygen species (ROS) eg. Ethyl alcohol, hydrogen peroxide. • RNA oxidation is more common than DNA oxidation. • Effects: Dysfunctioning in protein synthesis and eventually cell death.

24. CELL SWELLING

25. CELL SWELLING • It is an intracytoplasmic accumulation of water due to incapacity of the cells to maintain the ionic and fluid homeostasis. • It is the first manifestation of cellular injury. • Causes:Cellular hypoxia (inadequate oxygen), Hypokalemia. • Effects: Damage to the sodium potassium pump, Increase in weight of the organ, cell necrosis.

26. INTRACELLULAR ACCUMULATION

27. Cells accumulate abnormal amounts of various substances which may be harmful to the cell. • The substance may be located in nucleus or within cytoplasm or within organelles (typically lysosomes).

28. Mechanism of Intracellular accumulation • A normal substance is produced at normal or increased rate but the metabolic rate is inadequate to remove it. Eg. Fatty change in liver.

29. 2) A normal or abnormal substance accumulates because of genetic defects in folding, packaging, transport or secretion.

30. 3) An inherited defect in enzyme results in failure to degrade metabolites – known as storage diseases.

31. 4) Absence of enzyme machinery to degrade the abnormal exogenous substances. Eg silica or carbon

32. Example of Intracellular accumulation Fatty change in liver (Steatosis) • It refers to any abnormal accumulations of triglycerides within cells. • Commonly seen in liver as it is the major organ of fat metabolism but also may occur in heart, kidneys, muscles. • Causes: Protein malnutrition, toxins (alcohol), diabetes mellitus, obesity.

33. CALCIFICATION

34. Calcification is the abnormal deposition of calcium salts together with small amounts iron, magnesium and other minerals. • 2 Types of Calcification • Dystrophic calcification- is calcium deposition in dead or dying tissues & occurs in the absence of calcium metabolic dearrangementsie. with normal serum levels of calcium. • Metastatic calcification-is calcium in normal tissues & occurs in dearrangements in calcium metabolism (hypercalcemia)

35. CELL DEATH ACIDOSIS AND ALKALOSIS

36. Normal body pH=7.4& this level is very important for normal biological activity. • On an average, the pH range may fluctuate from 7.35-7.45. • During normal metabolic activity, body produces both acid and bases but the acid production is greater than the base production.

38. ACIDOSIS – decline in blood pH (less than 7.35). ALKALOSIS – rise in blood pH (more than 7.45).

39. Acidosis- a decline in blood pH ↓ • Metabolic acidosis: due to a decrease in bicarbonate. ↓ • Respiratory acidosis: due to an increase in carbonic acid. ↑ • Alkalosis- a rise in blood pH ↑ • Metabolic alkalosis: due to an increase in bicarbonate.↑ • Respiratory alkalosis: due to a decrease in carbonic acid. ↓