4. Trauma and Cell Injury Modified Remisha.pptx

Pathophysiology

1. Trauma and Cell Injury

2. Discuss trauma Explain the process of cell injury Discuss reversible and irreversible cell injury Describe mechanisms of cell injury Hypoxic Free radical Chemical Physical Nutritional Discuss cell death in terms of Mechanisms and types of necrosis Mechanisms and significance of apoptosis

3. CELL INJURY

4. Homeostasis - normal cells have a fairly narrow range of function and steady state Cell adaptation- Excess physiological and pathological stress may force the cell to a new steady state. Adaptations are reversible functional and struct ural responses stress. Injury- Too much stress exceeds cell adaptive capacity, and compromises its essential cellular functions, it is called cell injury.

5. Key concepts Cell injury can be reversible or irreversible. The consequences of cell injury depend on the type, state, and adaptability of the injured cell and on type, severity and duration of injury Cell death is the result of irreversible injury

6. Cell response to Injury Recovery Adaptation Cell Death

7. Progression of cell injury

8. Causes of cell injury Hypoxia Ischemia Hypoxemia Loss of oxygen carrying capacity Chemicals,drugs,toxins Infections Physical agents - mechanical trauma extremes of temperature (burns and deep cold), radiation electric shock Immunologic reactions Genetic abnormalities Nutritional imbalances

9. Mechanism of Cell injury The principle targets of injurious stimuli are mitochondria, cell membranes, the machinery of protein synthesis and secretion, (RER) DNA.

10. Mechanism of Cell injury

11. CELL DEATH

12. Cell Death There are two principal types of cell death, necrosis and apoptosis , which differ in their mechanisms, morphology, roles in physiology and disease

13. NECROSIS A pathologic process in which cellular membranes are destroyed, enzymes and other constituents leak out, local inflammation is induced to clear the damaged cells.

14. Morphology of NECROSIS Morphologic features are: eosinophilia nuclear shrinkage, fragmentation, and dissolution; breakdown of plasma membrane and organellar membranes; leakage and enzymatic digestion of cellular contents

15. Patterns of tissue necrosis: Under different conditions, necrosis in tissues may assume specific patterns: coagulative, liquefactive, gangrenous, caseous, fat

16. Coagulative

17. Liquifactive necrosis

18. Fat Necrosis

19. Caseous Necrosis

20. Apoptosis Apoptosis is a type of cell death that is induced by a tightly regulated suicide program in which cells activate intrinsic enzymes that degrade the cells DNA and nuclear and cytoplasmic proteins.

21. Physiologic Apoptosis Apoptosis is important in the following physiologic situations: • The removal of supernumerary cells (in excess of the required number) during development. • Involution of hormone-dependent tissues on hormone withdrawal • Elimination of potentially harmful self-reactive lymphocytes to prevent immune reactions against one’s own tissues. • Death of host cells that have served their useful purpose, such as neutrophils in an acute inflammatory response, and lymphocytes at the end of an immune response.

22. Apoptosis in Pathologic Conditions Apoptosis eliminates cells that are injured beyond repair without eliciting a host reaction. DNA Damage Misfolded proteins Viral Infections

23. Mechanism of Apoptosis • Initiated by two major pathways: Mitochondrial (intrinsic) pathway Death receptor (extrinsic) pathway

24. Mitochondrial (intrinsic) pathway (Mechanism) In viable cells, anti apoptotic proteins (BCL2) prevent apoptosis. Mitochondrial (intrinsic) pathway is triggered by loss of survival signals, DNA damage,accumulation of misfolded proteins. This leads to leakage of pro-apoptotic proteins ( Cytochrome c) from mitochondrial membrane into the cytoplasm. Caspase cascade is activated that mediates the final phase of apoptosis and promotes fragmentation of nuclei. The formation of apoptotic bodies breaks cells up into “bite-sized” fragments that are removed by phagocytes.

25. Mitochondrial (intrinsic) pathway (Mechanism)

26. The Extrinsic (Death Receptor–Initiated) Pathway of Apoptosis This pathway is initiated by engagement of plasma membrane death receptors. Binding of Death Receptor to its Ligand activates Caspases. Caspases mediate apoptosis.