CELL INJURY, CELL DEATH, AND aging.pptx

pathology chapter 1

1. CELL INJURY AND ADAPTATIONS

2. CELLULAR RESPONSES TO STRESS AND NOXIOUS STIMULI As cells encounter physiologic stresses or pathologic stimuli, they can undergo adaptation , achieving a new steady state and preserving viability and function. The principal adaptive responses are Hypertrophy Hyperplasia Atrophy Metaplasia. 1/20/2025 2

3. Hypertrophy It is an increase in the size of cells and consequently an increase in the size of the organ. Cells are bigger and enlarged by an increased synthesis of structural proteins and organelles. Hypertrophy can be physiologic or pathologic Caused by increased functional demand or by specific hormonal stimulation . Hypertrophy and hyperplasia can also occur together. 1/20/2025 3

4. Physiologic cellular hypertrophy Enlargement of uterus during pregnancy as a result of excessive estrogen stimulation. weight lifter hypertrophy of individual skeletal muscle cells an increased workload. Pathologic cellular hypertrophy Cardiac enlargement due to: -Hypertension. - Valve disease. -Myocardial infarction. 1/20/2025 4

5. Hyperplasia Hyperplasia constitutes an increase in the number of cells in an organ or tissue. Hypertrophy and hyperplasia are closely related and often develop concurrently. Hyperplasia can be physiologic or pathologic. 1/20/2025 5

6. Physiologic hyperplasia Hormonal hyperplasia Eg . proliferation of the glandular epithelium of the female breast. Compensatory hyperplasia Eg . Hepatectomy , wound healing Pathologic hyperplasia Excessive hormonal or growth factor stimulation Eg . Endometrial hyperplasia, goiter, acromegaly 1/20/2025 6

7. Atrophy Shrinkage in the size of the cell by the loss of cell substance is known as atrophy. The entire tissue or organ diminishes in size, becoming atrophic. Atrophic cells may have diminished function, but they are not dead. Apoptotic death may also be induced by the same signals that cause atrophy 1/20/2025 7

8. Causes of atrophy Decreased workload, Loss of innervation, Diminished blood supply, Inadequate nutrition, Loss of endocrine stimulation Aging 1/20/2025 8

9. Metaplasia Metaplasia is a reversible change in which one adult cell type (epithelial or mesenchymal ) is replaced by another adult cell type. The cells are sensitive to a particular stress are replaced by other cell types better able to withstand the adverse environment . 1/20/2025 9

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11. CELL INJURY Cell injury results when cells are stressed so severely that they are no longer able to adapt or when cells are exposed to inherently damaging agents or suffer from intrinsic abnormalities (e.g., in DNA or proteins ) Different injurious stimuli affect many metabolic pathways and cellular organelles. Injury may progress through a reversible stage and culminate in cell death 1/20/2025 11

12. Con’t …..cell injury Reversible cell injury . In early stages or mild forms of injury the functional and morphologic changes are reversible if the damaging stimulus is removed Cell death With continuing damage, the injury becomes irreversible , at which time the cell cannot recover and it dies There are two types of cell death—necrosis and apoptosi s 1/20/2025 12

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14. Necrosis When damage to membranes is severe, enzymes leak out of lysosomes, enter the cytoplasm, and digest the cell Necrosis is the major pathway of cell death in many commonly encountered injuries, such as those resulting from ischemia, exposure to toxins, various infections , and trauma Cellular contents also leak through the damaged plasma membrane into the extracellular space, where they elicit a host reaction ( inflammation) necrosis is always a pathologic process 1/20/2025 14

15. Apoptosis When a cell is deprived of growth factors, or the cell’s DNA or proteins are damaged beyond repair, typically the cell kills itself Apoptosis serves many normal functions and is not necessarily associated with pathologic cell injury. It does not elicit an inflammatory response 1/20/2025 15

16. Features Necrosis Apoptosis Cell size 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 Intact; may be released in apoptotic bodies Adjacent inflammation Frequent No Physiologic or pathologic role Invariably pathologic Either of two Features of Necrosis and Apoptosis 1/20/2025 16

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18. CAUSES OF CELL INJURY The stress that can induce cell injury range from physical trauma , a motor vehicle accident to the single gene defect Grouped into the following broad categories: Oxygen Deprivation ( Hypoxia , or oxygen deficiency) Interferes with aerobic oxidative respiration and Common cause of cell injury and death 1/20/2025 18

19. Chemical Agents. Any chemical substance can cause injury Glucose Salt Water Poisons Air pollutants Insecticides Co Asbestos Ethanol. Therapeutic Drugs 1/20/2025 19

20. Infectious Agents. Submicroscopic viruses to meter-long tapeworms; The rickettsiae , bacteria, fungi, and protozoans Immune reactions: intended or incidental. Anaphylaxis to a foreign protein or a drug. autoimmune diseases 1/20/2025 20

21. Genetic Defects. Congenital malformations associated with Down syndrome The single amino acid substitution in the hemoglobin S of sickle cell anemia. Inborn errors of metabolism 1/20/2025 21

22. Nutritional Imbalances. Nutritional deficiencies remain a major cause of cell injury. Protein-calorie insufficiency. Specific vitamin deficiencies 1/20/2025 22

23. Physical Agents. Trauma, Extremes of temperatures, Radiation, Electric shock Sudden changes in atmospheric pressure 1/20/2025 23

24. Necrosis Necrosis is the type of cell death that is associated with loss of membrane integrity and leakage of cellular contents culminating in dissolution of cells, largely resulting from the degradative action of enzymes on lethally injured cells . The leaked cellular contents often elicit a local host reaction, called inflammation 1/20/2025 24

25. Patterns of Tissue Necrosis There are several morphologically distinct patterns of tissue necrosis, which may provide clues about the underlying cause - Coagulative - C aseous - Liquefactive -Fat -Gangrenous - Fibrinoid 1/20/2025 25

26. Coagulative necrosis is a form of necrosis in which the underlying tissue architecture is preserved for at least several days Presumably the injury denatures not only structural proteins but also enzymes, thereby blocking the proteolysis of the dead cells; as a result, eosinophilic , anucleate cells may persist for days or weeks. 1/20/2025 26

27. con’t … coagulative Leukocytes are recruited to the site of necrosis, and the dead cells are digested by the action of lysosomal enzymes of the leukocytes and cellular debris is then removed by phagocytosis. Coagulative necrosis is characteristic of infarcts (areas of ischemic necrosis) in all of the solid organs except 1/20/2025 27

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29. Liquefactive necrosis I s seen in focal bacterial or, occasionally , fungal infections , because microbes stimulate the accumulation of inflammatory cells and the enzymes of leukocytes digest (“liquefy”) the tissue. Hypoxic death of cells within the central nervous system often evokes liquefactive necrosis 1/20/2025 29

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31. Gangrenous Necrosis It usually refers to the condition of a limb, generally the lower leg, that has lost its blood supply and has undergone coagulative necrosis involving multiple tissue layers. When bacterial infection is superimposed, coagulative necrosis is modified by the liquefactive action of the bacteria and the attracted leukocytes (resulting in so-called wet gangrene ) 1/20/2025 31

32. Caseous necrosis It is encountered most often in foci of tuberculous infection. Caseous means “cheese-like ,” referring to the friable yellow-white appearance on the area of necrosis Unlike with coagulative necrosis , the tissue architecture is completely obliterated and cellular outlines cannot be discerned 1/20/2025 32

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34. Fat necrosis refers to focal areas of fat destruction, typically resulting from release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity Fibrinoid necrosis is a special form of necrosis, visible by light microscopy, usually in immune reactions in which complexes of antigens and antibodies are deposited in the walls of arteries e.g., in polyarteritis nodosa , rheumatic fever 1/20/2025 34

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36. Thank you Any questions????