1. Cell Biology Review and Altered Functions

3. Embryonic Stem Cells

4. Man Made Stem Cells

5. Adult Stem Cells

6. Major Parts

7. Eukaryotic Cell Structure

8. Cell Functions Communicate Absorb Secrete Excrete Respire Move Conduct Reproduce

9. What is the “Brain” of the cell?

10. Cell Membrane (“membrain”) Structure Function Receptors Junctions Signal Transduction Transport Gradients  Concentration Dependent Independent  Electrical  Pressure

11. Bulk Transport

12. Cell Membrane Proteins

13. Na+/K+ Pump

14. Cell Junctions

15. Adhesion Molecules Cell Adhesion Molecules (CAM)  Bind growth factors Cadherins  Bind cell membranes to form junctions Selectins  Bind WBCs during inflammatory reactions Integrins  Binds extra cellular matrix proteins

16. Cell Junctions

17. Cancer Metastasis

18. Cell Signals

19. Hormone vs. Neurotransmitter

20. Target Cell

21. Receptors

22. Cell Receptor Summary

23. Abnormal Intercellular Communication Alterations in  Membrane: enzymes, ions reactive oxygen species (ROS)  Adhesion molecules: defense, clotting, metastasis  Gradients: water, ions, glucose  Transport Proteins: pumps, channels  Signaling molecules: hyper/hypo production  Receptors: destroyed, blocked, triggered

24. Mitochondria

25. Cellular Metabolism Macromolecules Energy Requirements:  BMR,  TMR Energy Forms Metabolic Pathways  Glycolysis  Aerobic Respiration  Beta Oxidation  Deamination

26. Metabolic Pathways: Aerobic Krebs Cycle

27. Metabolic Pathways: Proteins & Lipids

28. Metabolism Summary

29. Metabolic Alterations Alterations  Impaired Input Malnutrition Malabsorption  Impaired Balance Hypoxia Toxicity Trauma Genetic  Demand Changes Hypometabolic State Aging, Immobility Hypermetabolic State Pregnancy Hypothermia Wound healing Stress Alcohol Metabolism

30. Cell Cycle

32. Cell Divisions Compared

33. Tissue Types

34. Tissues Repair  Regeneration  Scar Tissue Death  Apoptosis  Necrosis

35. Mechanisms of Cellular Injury Response depends on  Type of injury  Duration  Severity Consequences depend on  Type of cell  Current physiology of cell  Adaptability Vulnerable cell sites  Cell Membrane  Mitochondria  Nucleus Hypoxia Ischemia Oxidants

36. Causes of Cellular Injury Physical Chemical Microbial Immunologic Genetic Nutritional Aging

37. Toxic, Chemical, or Physical Injury Chemical  Environmental agents  Drugs  Metabolites Physical  Trauma  Temperature  Radiation

38. Heat Injury to RBCs

39. Pathogenesis example

40. Sequella to injury

41. Changes due to injury

42. Reversible Injury Processes Transient if stress is removed Compensatory responses  Full capacity to repair  Adaptation with diminished capacity Cell Responses  Cell swelling (hypertrophy) Na+/K+ pump damaged Osmosis  Fatty changes Cell metabolism changes Severe injury Slower to recover

43. Reversible Injury in the Liver Gross Findings  Greasy  Pale  Enlarged Cellular Metabolism Stops  Disruption of Beta Oxidation  FA  Triglycerides  Cytoplasmic fat droplets Fatty Liver

44. Hypoxia and Ischemia Define Hypoxia End results  ATP production changes  Anaerobic mechanisms  pH changes Organ Diseases  Lungs  Heart  Blood Vessels  Blood Define Ischemia End results  Hypoxia  Infarct Organ problems  Arteries  Veins

45. Ischemia  Infarct  Necrosis Coagulative necrosis in the kidney

46. Ischemia Pathway

47. Reversible Injury from Hypoxia/Ischemia Decreased Oxidative phosphorylation Decreased ATP Depletion of glycogen Decreased pH Decreased protein synthesis Electrolyte changes  Na+  K+  Ca++ Increased osmosis Swollen organelles Small Intestine

48. Stress and Intracellular Changes Cytoskeleton Lysosomes Mitochondria SER Intracellular accumulations  Fat  Protein  Glycogen  Pigments  Cholesterol

49. Stressors and Cell Death

50. Lipofuscin Pigment in hepatocytes

51. Irreversible Injury from Hypoxia/Ischemia Cell Membrane injury Free radical formation Lipid breakdown Lysosomal enzyme release  Ribosomes  Nuclear changes  Protein digestion Ca++ accumulates in mitochondria Activation of Inflammatory chemicals Lung

52. Pathological Calcification Dystrophic Calcification  Occurs in dead, dying, or damaged tissue Atherosclerosis Heart Valves Metastatic Calcification  Occurs in hypercalcemic states Renal Failure Secondary Hyperparathyroidism

53. Free Radical Formation and Damage

54. Effects of Oxidative Stress

56. Enzymes involved in Oxidative Stress

57. Mitochondrial Function and Damage

58. Mitochondrial Damage Release of Cytochrome C

59. Mitochondrial Changes in Injury

60. DNA damage

61. Antioxidants

62. Reversible vs Irreversible Damage Cardiac Function

63. Cellular Adaptations Physiologic  Up or down regulation  Protein synthesis  Atrophy  Hypertrophy  Hyperplasia Pathological  Atrophy  Hypertrophy  Hyperplasia / Dysplasia  Metaplasia

64. Atrophy

65. Hypertrophy

66. Hypertrophic Cardiomyopathy

67. Hyperplasia

68. Metaplasia and Dysplasia

69. Necrosis Morphological Types Coagulative Necrosis  Protein coagulation due to acidosis  MI Liquefactive Necrosis  Complete digestion of dead cells  Nervous system, Bacterial and Fungal Diseases Gangrenous Necrosis  Ischemic coagulative necrosis  Post op Caseous Necrosis  Amorphous granular debris (cheese like appearance)  TB infections Fat Necrosis  Fat destruction due to liquefaction  Fatty acids combine with calcium to create chalky white areas (saponification)  Pancreatitis

70. Liquefactive Necrosis in the brain

71. Necrosis

72. Caseous Necrosis (lung)

73. Gangrenous Necrosis Skin

74. Apoptosis

75. Differences between cell death: Necrosis and Apoptosis Necrosis  Contiguous cells  Membrane loss  Gradient changes  Organelles swell  Nucleus Pyknosis (shrinks) Karyorrhexis (fragment) Apoptosis  Individual cells  Normal process  Cells shrink  Fragmented bodies  Phagocytosis

76. Factors in Cell Death

77. Necrosis stimulates inflammation

78. Tissue Repair Tissue Types  Parenchymal (fxn)  Stromal (CT) Repair  Regenerate  Replacement Regenerating Ability  Labile cells  Stable cells  Permanent cells

79. Tissue Repair and Chronic injury

80. Cellular Aging Theories Cellular Senescence Loss of redundant DNA sequences Radom errors/mutations/repair Free Radical Damage Telomere Shortening Decreased heat shock response Glycosylation of proteins and NA Metabolic Rate (inverse) Homeostatic Systems decline

81. Cellular Damage vs Repair Cycle

82. Summary of Cellular Damage Events

83. Examples of some Diseases/Conditions Caused by alterations In Cell Function

84. Questions?