Altered Cellular and Tissue Biology

1. Altered Cellular and Tissue Biology Chapter 2

2. stresses affect normal cell function failure to maintain function adaptive injury changes to maladaptive maintain cell changes function death

3. Types of Cellular Adaptation

4. Cellular Adaptation • Cells adapt to their environment to • Escape • Protect themselves from injury • An adapted cells is neither normal nor injured • Somewhere in between • The most significant adaptive changes include • Atrophy • Hypertrophy • Hyperplasia • Metaplasia

5. Cellular Adaptation • Allows the stressed tissue to survive or maintain function • Atrophy • Hypertrophy • Hyperplasia • Metaplasia • Dysplasia

6. ATROPHY A decrease or shrinkage in cellular size

7. Atrophy • Entire organ can also shrink if enough cells shrink • Most common in skeletal muscle, heart, secondary sex organs, and brain • Often due to chronic malnutrition – “self-eating”

8. Atrophy • May be due to Physiologic Changes • Thymus goes through atrophy during childhood • May be due to Pathologic Changes • Decrease in workload, use pressure, blood supply, hormonal stimulation • Disuse atrophy of skeletal muscles • Aging of the brain cells

10. Normal Liver Cells

11. Here is the centrilobular portion of liver next to a central vein. The cells have reduced in size or been lost from hypoxia. The pale brown-yellow pigment is lipochrome that has accumulated as the atrophic and dying cells undergo autophagocytosis.

12. Atrophy • Muscle cells contain less • RER • Mitochondria • Myofilaments • Can be caused by nerve loss, decreased oxygen consumption or amino acid consumption

13. Normal Cardiac Muscle

14. Atrophy; Cardiac Muscle

15. Atrophy • May be caused by • Decreased protein synthesis • Increased protein catabolism • Both • Malnutrition atrophy is accompanied by “self-eating” or autophagy • Autophagic vacuoles • Rapid increase in hydrolytic enzymes • Lipofuscin resists autophagy and accumulates in cells – shows you the cell is old

16. HYPERTROPHY • Increase in the size of cells, and hence the size of the organ.

17. Hypertrophy • Due to increases in • RER • Protein synthesis • Mitochondria and • NOT cellular fluid

18. HYPERTROPHY may be due to Hormonal (physiological) demand Increased functional demand It is an adaptive response Muscles can’t adapt to increased metabolic demands by mitotic division and production of new cells

19. Hypertrophy • During pregnancy – hormone induced hypertrophy • Muscular enlargement – heart and skeletal • Can’t increase by mitotic division or production of new cells • Advanced hypertrophy can lead to myocardial failure

20. Hypertrophy of the muscles of an athlete                                                       

21. Cardiac Muscle • Myocardial hypertrophy • Caused by dilation of the cardiac chambers • Is short-lived • Followed by increased synthesis of cardiac muscle proteins • Advanced hypertrophy can lead to myocardial failure

22. Hypertrophy of cardiac muscles

25. Hypertrophy of the Uterus

26. HYPERPLASIA An increase in the number of cells in a tissue or organ. It occurs in tissues with cells that are capable of mitotic division

27. Hyperplasia • A response to cellular injury that is severe and prolonged • Production of growth factors • Hypertrophy and hyperplasia often occur together. • In non-dividing cells (myocardial fibers) only hypertrophy occurs

28. Compensatory Hyperplasia • Adaptive mechanism that enables organs to regenerate • Remove 70% of the liver and it will regenerate in about 2 weeks. • Hepatocyte Growth Factor (HGF), Transforming growth factor (TGF-α), tumor necrosis factor-α (TNF-α) • Nerve, skeletal muscle, myocardial cells and lens cells of the eye do not regenerate and do not go through hyperplasia • A callus is an example of hyperplasia

29. Hormonal Hyperplasia • Occurs chiefly in Estrogen-dependent organs • Uterus and breast • Estrogen stimulates endometrial growth

30. Pathologic Hyperplasia • The abnormal proliferation of normal cells • Can occur as a response to excessive hormonal stimulation or effects of growth factors • Cells have pronounced nuclear enlargement, clumping of chromatin and one or more enlarge nucleoli • An example is excessive endometrial growth

34. Dysplasia • Abnormal changes in the size, shape and organization of mature cells • Not a true adaptive process • Atypical hyperplasia

35. Dysplasia • Frequently encountered by epithelial tissue of the cervix and respiratory tract • Often found adjacent to cancerous cells • The term dysplasia does NOT indicate cancer and may NOT progress to cancer

36. Dysplasia • Classified as • Mild • Moderate • Severe • Can be a strong predictor of breast cancer development

37. Squamous Cell Dysplasia

38. METAPLASIA • A reversible change in which one adult cell type replaced by another adult cell type. • Conversion of a differentiated cell type into another. • An example is replacement of normal columnar ciliated cells of the bronchial lining by stratified squamous cells that do not secrete mucous or have cilia • Usually induced by cigarette smoking • Can be reversed????

41. Definitions • Hyperplasia -  Number of cells • Prostate • Endometrium • Breast ducts • Hypertrophy -  SIZE of cells • Myocardium • Muscle fibres • Metaplasia – Change of cell TYPE • Cervical where glandular → squamous epithelium • Bronchioles where glandular → squamous epithelium • Dysplasia – Abnormal Development, size, shape, arrangement • Cervical • Fibrous • V tumour, metastasis, carcinogen

42. WHAT CAUSES CELLULAR INJURY?

43. CELLULAR INJURY • Reversible injury • Injured cell may recover • Irreversible injury • Cell will die • Cellular injury is usually caused by exposure to: • Hypoxia • Toxic chemicals • Infections

44. Reversible vs irreversible injury Fatty change Cellular swelling Karyolysis- the dissolution of the nucleus - the nucleus swells and gradually loses its chromatin. Pyknosis - Shrunken nucleus with condensed chromatin. Karyorrhexis - rupture of the cell nucleus in which the chromatin disintegrates into formless granules that are extruded from the cell. Coagulative necrosis Liquefactive necrosis Caseous necrosis Fat Necrosis

45. HYPOXIA a lack of sufficient oxygen the most common cause of cell injury and death.

46. Hypoxia Causes ATP Depletion or“Power Failure” • Aerobic metabolism stops  less ATP is produced • Na+/K+ ATPase cannot run fast enough • Cell swells up with water • Anaerobic metabolism used  lactic acid produced • Acid damages cell membranes, intracellular structures, and DNA

47. Two Boys Suffered Hypoxia • One was at a normal body temperature • The other one was very cold • Which one will have a lower intracellular pH? • Which one will have more cell swelling? • Why?

48. CAUSES OF HYPOXIA • ISCHAEMIA • HYPOXAEMIA • FAILURE OF THE CYTOCHROMES • POOR NUTRITION • INFECTIOUS AGENT • IMMUNE INJURY • CHEMICAL AGENTS • PHYSICAL AGENTS

49. Ischemia ("ischemic hypoxia"; "stagnant hypoxia"): Loss of arterial blood flow (literally, "holding back the blood") Local causes Occlusion of the arteries that bring in fresh blood Occlusion of the veins which allow blood to leave, so that fresh blood can flow in Shunting of arterial blood elsewhere ("steal syndromes"; "Robin Hood" syndromes) Systemic causes Failure of the heart to pump enough blood

50. Hypoxemia: Too little available oxygen in the blood • Oxygen problems ("hypoxic hypoxia") • Too little oxygen in the air • Failure to properly ventilate the lungs • Failure of the lungs to properly oxygenate the blood • Failure of the heart to pump enough blood through the lungs • Tremendously increased dead space (i.e., pulmonary thromboembolus)