1. CELL ADAPTATIONS CELL INJURY CELL DEATH DR.SAMINA QAMAR AP PATHOLOGY.

2. OBJECTIVES Understand the concepts of cellular growth adaptations---Hyperplasia, Hypertrophy, Atrophy, Metaplasia, Dysplasia Reversible, irreversible cell injury

3. OBJECTIVES Understand the pathologic mechanisms at the SUB-cellular level---ATP, Mitochondria, Ca++, Free Radicals, Membranes Understand and differentiate the concepts of APOPTOSIS and NECROSIS Understand SUB-cellular responses to injury---Lysosomes, Smooth endoplasmic reticulum, Mitochondria, Cytoskeleton

4. OBJECTIVES Identify common patterns of cellular swelling and fatty change. Cell aging

5. To maintain a steady state of structure and function is HOMEOSTASIS

6. Cellular response to injury Non-lethal injury: cell will adapt Hypoxia, chemical injury, infection: Reversible injury will result in fatty change. Irreversible injury will result in death Repeated Injury: cellular aging

7. ADAPTATIONS: Non-lethal injury. Altered/changed steady state in structure and function of cell. WHY: In response to physical/ pathological stimuli. Increased or decreased stimulation or any irritation.

8. The –plasia brothers HYPER- HYPO- (A-) NORMO- META- DYS- ANA- “Frank” ANA-

9. HYPER-PLASIA IN-CREASE IN NUMBER OF CELLS, if they can divide.

10. Examples: Endometrium,breast,liver.

11. The –trophy brothers HYPER- HYPO- (A-) DYS-

12. HYPER-TROPHY IN - CREASE IN SIZE OF CELLS

13. Examples:Myocardium, Myometrium, Muscle

14. Hypertrophy v/s Hyperplasia.

15. Can both occur simultaneously?

16. A-TROPHY*? DE - CREASE IN SIZE OF CELLS? YES SHRINKAGE IN CELL SIZE DUE TO LOSS OF CELL SUBSTANCE

17. ATROPHY DECREASED WORKLOAD DENERVATION DECREASED BLOOD FLOW DECREASED NUTRITION AGING (involution) PRESSURE “EXHAUSTION”

18. Examples: Brain, Muscle.

19. METAPLASIA A SUBSTITUTION of one NORMAL CELL or TISSUE type, for ANOTHER –COLUMNAR  SQUAMOUS (Cervix) –SQUAMOUS  COLUMNAR (Esophagus) –FIBROUS  BONE –WHY?

20. Examples: Respiratory epithelium, Barrett’s, myositis ossificans.

21. Dysplasia: disorganized epithelium.

22. Dysplasia:

23. Normal-hyperplasia-dysplasia- carcinoma.

24. CELL DEATH

25. What is DEATH? –DEATH is IRREVERSIBLE –But in cell its either reversible or irreversible. APOPTOSIS vs. NECROSIS

26. REVERSIBLE CHANGES REDUCED oxidative phosphorylation ATP depletion Cellular “SWELLING”

27. IRREVERSIBLE CHANGES MITOCHONDRIAL IRREVERSIBILITY IRREVERSIBLE MEMBRANE DEFECTS LYSOSOMAL DIGESTION

28. REVERSIBLE = INJURY IRREVERSIBLE = DEATH SOME INJURIES CAN LEAD TO DEATH IF PROLONGED and/or SEVERE enough

29. CELL DEATH APOPTOSIS (“normal” death) programmed death. NECROSIS (“premature” or “untimely” death

30. Death is of two types

33. INJURY CAUSES (REVERSIBLE) Hypoxia, (decreased O2) PHYSICAL Agents CHEMICAL Agents INFECTIOUS Agents Immunologic Genetic Nutritional

34. CHEMICAL INJURY “Toxic” Chemicals, e.g CCl4 Drugs, e.g tylenol Dose Relationship Free radicals, organelle, DNA damage

35. INJURY MECHANISMS (REVERSIBLE) DECREASED ATP MITOCHONDRIAL DAMAGE INCREASED INTRACELLULAR CALCIUM INCREASED FREE RADICALS INCREASED CELL MEMBRANE PERMEABILITY

36. What is Death? What is Life? DEATH is –IRREVERSIBLE MITOCHONDRIAL DYSFUNCTION –PROFOUND MEMBRANE DISTURBANCES LIFE is……..??? Till death hasn’t occurred.

37. DEATH: ELECTRON MICROSCOPY B-Microvillus incorporated in cell, Blebs extruded from cell. C- Mitochondrial swelling.

38. DEATH:PINK IN LIGHT MICROSCOPY Nuclei

39. LIQUEFACTIVE NECROSIS, BRAIN

40. FIBRINOID NECROSIS

41. APOPTOSIS: falling off. NORMAL (preprogrammed) PATHOLOGIC (associated with Necrosis)

42. “NORMAL” APOPTOSIS Embryogenesis Hormonal “Involution” Cell population control, e.g., “crypts” Post Inflammatory “Clean-up” Elimination of “HARMFUL” cells Cytotoxic T-Cells cleaning up

43. “PATHOLOGIC” APOPTOSIS “Toxic” effect on cells, e.g., chemicals, pathogens Duct obstruction Tumor cells Apoptosis/Necrosis spectrum

44. APOPTOSIS MORPHOLOGY DE-crease in cell size, i.e., shrinkage IN-crease in chromatin concentration, i.e., hyperchromasia, pyknosis  karyorhexis  karyolysis IN-crease in membrane “blebs” Phagocytosis

45. SHRINKAGE/HYPERCHROMASIA Karryorhexis, karryolysis.

46. PHAGOCYTOSIS

48. Damaged/necrotic cells can accumulate fat: Fatty change Commonly occurs in Liver, heart. Due to defective uptake, catabolism or secretion of lipid. Severe fatty change can alter cellular structure and function. Seen in diabetes, alcoholism, obesity.

49. LIPID LAW ALL Lipids are YELLOW grossly and WASHED out (CLEAR) microscopically

50. FATTY LIVER

53. CELL AGING It is due to progressive decline in cellular function resulting from exposure to exogenous influences. Cell can undergo limited number of divisions and goes into non-dividing or senescence phase. Accumulation of metabolic and genetic changes that damage DNA.

54. TELOMERES Telomeres are sequences of DNA present at ends of chromosomes. They become shorter with every division. Once shortened they cannot protect ends of chromosome and appear as damaged DNA. Cell goes into cell cycle arrest.