1. Lecture # 20 CELL INJURY & RESPONSE-3 Dr. Iram Sohail Assistant Professor Pathology

2. OBJECTIVES Discuss mechanisms of injury under following headings – Depletion of ATP – Damage to mitochondria – Influx of calcium – Accumulation of Oxygen derived free radicals – Defects in membrane permeability – Damage to DNA & protein

3. 1.DEPLETION OF ATP ATPs are main energy store of cell. They are required for all the functions of cell. In cell injury the ATPs will decrease.

4. The main causes of ATP depletion are – Reduced supply of oxygen & nutrients – Mitochondrial damage – Toxins like Cyanide

5. Because of decreased ATP ----- the activity of ATP dependent sodium pump is reduced ------ resulting in accumulation of sodium and efflux of potassium ------- this influx of sodium also carries water with it ------ causes cell swelling

6. Also Compensatory increase in anaerobic glycolysis ------ lactic acid accumulation ------ intracellular PH will decrease

7. Also Because of failure of Ca pump ----Increased intracellular Ca will increase ----- and damage to cellular components Detachment of ribosomes from rough endoplasmic reticulum ------ decreased protein synthesis ----- irreversible injury ----- cell death

9. 2.DAMAGE TO MITOCHONDRIA ATPs are formed in mitochondria. Mitochondria can be damaged by decrease oxygen supply, increased Ca and reactive oxygen species.

10. When mitochondria is damaged ------ decreased ATPs------ and cell will go towards injury

12. 3.INFLUX OF CALCIUM Normally the intracellular calcium is lower than extracellular calcium. Because of decreased oxygen (ischemia) and toxins ----- influx of calcium occurs ------ intracellular calcium will increase ------- this calcium activates certain enzymes ----- these enzymes will cause cell injury.

13. These enzymes are – Phospholipases ------ cause membrane damage – Endonucleases ------ cause DNA damage

15. 4.ACCUMULATION OF OXYGEN DERIVED FREE RADICALS Oxygen derived free radicals are chemical species with unpaired electron in their outer orbit.

16. They cause injury by

17. 5.DEFECT IN MEMBRANE PERMEABILITY The cell membrane is damage by ischemia, microbes, physical and chemical agents The mechanism is

18. 6.DAMAGE TO DNA & PROTEINS Mainly radiation injury and free radical oxidative injury cause damage to DNA. Inherited mutations & free radical injury cause folding of proteins and ultimately damaging of proteins.