1. Cell Injury Cell and Tissue Adaptation Necrosis and Apoptosis Dr. Raid Jastania

2. Cell – Tissue – Organ – System

3. Intended Learning Outcomes: 1.Students should list all the causes of cell injury. 2.Students should understand how the concept of cell injury is useful in causation of diseases. Students should apply this concept to list the possible causes of diseases of any tissue or organ in the body. 3.Students should understand the consequences of cell injury and the targeted structures of the cell. 4.Students should know the morphologic changes in cell death (necrosis and apoptosis) 5.Students should understand the meaning of apoptosis and the major events in this process. 6. Students should know the types of adaptive responses and be able to give examples of each type.

4. What is Cell Injury? What is Cell Death? How does injury cause death?

5. Cell Injury and Cell Death Characteristics of Injury Type, Severity, Duration Characteristics of Cell Type, Status, Genetic makeup, adaptation

6. Causes of Cell Injury: 1.Infection 2.Physical injury 3.Chemical injury 4.Hypoxia/ ischemia 5.Nutritional 6.Immunologic 7.Genetic 8.Aging

7. Reversible Injury – Irreversible Injury – Functional defect – Structural Defect

8. There are 4 main structures that may be targeted by injury: 1.Cell membrane 2.Mitochondria (ATP production) 3.Protein 4.DNA (genetic material)

9. Biochemical mechanisms in cell injury: 1.ATP depletion 2.Mitochondrial damage 3.Plasma membrane permeability defect 4.Oxygen free radicals 5.Ca++ influx to the cell

10. Example of Cell Injury: Ischemic and Hypoxic Injury: Hypoxia vs. Ischemia 1.Stop of ATP-dependent Na-pump. Resulting in increase Na+ and water, and loss of K+. The end result is cell swelling. 2.Anaerobic glycolysis results in production of lactic acid and drop of pH 3.Later there is swell in of the rough endoplasmic reticulum and detachment of the ribosomes and reduction in protein synthesis. 4. After this stage there is influx of Ca++ and activation of catabolic enzymes with cell death.

11. Reperfusion Injury: 1.Increase Ca++ supply by blood and increase influx of Ca++ 2.Delivery of inflammatory cells which worsen the injury by there action 3.Increase in oxygen free radicals when oxygen is delivered to cells

12. Application: Cell Injury: Think of tissues or organs with a defect that results in cell death (eg. Ulcer of skin or mucosa, necrosis of liver, lung, and other organs…) List the causes of cell death in each of these tissues and organs.

13. Free Radical Induced Cell Injury: Free radicals are generated in the cell by: 1.Mitochondrial oxidation: superoxide (O2-), Hydrogen peroxide (H2O2), Hydroxil group (OH) 2.Metabolism of iron and copper 3.Nitric oxide 4.Radiation UV and x-ray

14. Free Radical Induced Cell Injury: How free radicals cause injury: 1.Lipid peroxidation 2.DNA fragmentation 3.Cross-linking of proteins

15. Free Radical Induced Cell Injury: How cells prevent injury by free radicals: 1.Superoxide dismutase 2.Glutathione peroxidase 3.Antioxidant (vit E, A, C) 4.Transport proteins (transferring)

16. Intended Learning Outcomes: 1.Students should list all the causes of cell injury. 2.Students should understand how the concept of cell injury is useful in causation of diseases. Students should apply this concept to list the possible causes of diseases of any tissue or organ in the body. 3.Students should understand the consequences of cell injury and the targeted structures of the cell. 4.Students should know the morphologic changes in cell death (necrosis and apoptosis) 5.Students should understand the meaning of apoptosis and the major events in this process. 6. Students should know the types of adaptive responses and be able to give examples of each type.