APOPTOSIS, NECROSIS and CANCER
LEARNING OBJECTIVES <ul><li>At the end of the lecture, students should be able to: </li></ul><ul><li>Know the importance o...
CELL DEATH <ul><li>Cells are born, </li></ul><ul><li>live for   a given period of time  </li></ul><ul><li>an d  then die  ...
Cell Injury <ul><li>A cell maintaining a steady state called Homeostasis </li></ul>
Cell Injury <ul><li>Altered Homeostasis </li></ul>
To die or not to die? <ul><li>Integrated balance between positive survival factors and negative death signals decides fate...
 
CELL DEATH <ul><li>The 100 trillion cells of the body are members of a highly organized community </li></ul><ul><li>The to...
APOPTOSIS   <ul><li>Apoptosis is an  energy dependent  </li></ul><ul><li>programmed  cell death  </li></ul><ul><li>for rem...
<ul><li>Programmed cell death during embryogenesis  </li></ul><ul><li>Formation of free and independent digits  </li></ul>...
<ul><li>Chronic viral diseases </li></ul><ul><li>Neurodegenerative diseases </li></ul><ul><li>Reperfusion injury </li></ul...
THE MECHANISMS OF APOPTOSIS <ul><li>This process involves a specific proteolytic cascade  </li></ul><ul><li>There are 3 di...
APOPTOSIS ;  MORPHOLOGIC CHANGES <ul><li>Early :  Chromosome condensation, cell body shrink  </li></ul><ul><li>Later :  Me...
Membrane blebs during apoptosis
THE ENZYMATIC REGULATION OF APOPTOSIS <ul><li>Apoptosis is initiated by activation of a family of </li></ul><ul><li>protea...
<ul><li>Excessive apoptosis </li></ul><ul><li>Uncontrolled cell loss </li></ul>
Diseases featuring excessive apoptosis <ul><li>Neurodegenerative </li></ul><ul><ul><li>Parkinson’s disease </li></ul></ul>...
<ul><li>Uncontrolled growth of cells </li></ul><ul><li>Insufficient apoptosis </li></ul>
Diseases featuring insufficient apoptosis <ul><li>Many cancers </li></ul><ul><li>Autoimmune Lymphoproliferative Syndrome (...
CLINICAL IMPORTANCE OF APOPTOSIS <ul><li>Recent studies suggest that abnormalities of apoptosis may play a  key role in ne...
NECROSIS   death by injury   <ul><li>cell death as the  result of injury, disease, or pathological state  </li></ul><ul><l...
COAGULATIVE NECROSIS <ul><li>Cell outlines remain intact  after cell death and can be observed by light microscopy </li></...
CASEOUS NECROSIS <ul><li>Tissues bear soft, granular, </li></ul><ul><li>friable appearance </li></ul><ul><li>cream-cheesy(...
LIQUEFACTIVE NECROSIS (OR COLLIQUATIVE NECROSIS) <ul><li>Necrotic degradation of tissue that  softens  and liquify tissues...
FAT NECROSIS <ul><li>results from the action of  lipases on fatty tissues  </li></ul><ul><li>Chalky yellow white deposits ...
FIBRINOID NECROSIS <ul><li>It is marked by deposition of  fibrin-like proteinaceous material in arterial walls , </li></ul...
DIFFERENCE B/W APOPTOSIS  AND NECROSIS <ul><li>APOPTOSIS  </li></ul><ul><li>Chromatin condensation  </li></ul><ul><li>•  C...
DIFFERENCE B/W APOPTOSIS  AND NECROSIS
CANCER; INTRODUCTION <ul><li>Neoplasm - (new growth)  abnormal mass of tissue, the growth of which exceeds and is uncoordi...
Diseases featuring excessive apoptosis <ul><li>Neurodegenerative </li></ul><ul><ul><li>Parkinson’s disease </li></ul></ul>...
CANCER <ul><li>Cancer  is  a  disorder of cellular homeostasis   disease in which there is  uncontrolled cell division  ca...
CANCER <ul><li>The abnormal genes are called  oncogenes. </li></ul><ul><li>Also present in all cells are  antioncogenes , ...
CARCINOGENS <ul><li>Ionising radiation   – X Rays, UV light </li></ul><ul><li>Chemicals  – asbestos, </li></ul><ul><li>tar...
HALLMARKS OF CANCER
BENIGN OR MALIGNANT? <ul><li>Benign tumours </li></ul><ul><li>do not spread from their site of origin </li></ul><ul><li>ca...
<ul><li>Malignant tumours </li></ul><ul><li>can spread from the original site and cause  secondary tumours . </li></ul><ul...
GENERAL AND LOCAL EFFECTS OF CANCER <ul><li>Cancer can kill the patient by: </li></ul><ul><li>Local effects </li></ul><ul>...
REFERENCES <ul><li>Text book of medical physiology , Guyton and Hall </li></ul><ul><li>Robbins & Cotran Pathologic Basis o...
SELF ASSESSMENT <ul><li>Q1. Is cell death necessary? why? </li></ul><ul><li>Q2. Which type of cell death is called program...
SELF ASSESSMENT <ul><li>Q4. Identify the type of necrosis in fig A& B </li></ul><ul><li>A  B </li></ul>
<ul><li>Q5. Name some of the common carcinogens. </li></ul><ul><li>Q6. Differentiate b/w benign and malignant tumors. </li...
 
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11.20 (dr. yasmeen hashim) apoptosis (mechanism in normal tissues. programmed cell death) necrosis cancer cell growth

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11.20 (dr. yasmeen hashim) apoptosis (mechanism in normal tissues. programmed cell death) necrosis cancer cell growth

  1. 1. APOPTOSIS, NECROSIS and CANCER
  2. 2. LEARNING OBJECTIVES <ul><li>At the end of the lecture, students should be able to: </li></ul><ul><li>Know the importance of cell death. </li></ul><ul><li>Define various modes of cell death. </li></ul><ul><li>Identify features of necrosis, apoptosis. </li></ul><ul><li>Differentiate between necrosis and apoptosis. </li></ul><ul><li>Define cancer </li></ul><ul><li>Describe the mechanism </li></ul><ul><li>of cancer development </li></ul>
  3. 3. CELL DEATH <ul><li>Cells are born, </li></ul><ul><li>live for a given period of time </li></ul><ul><li>an d then die </li></ul><ul><li>Bowen, 1998 </li></ul>
  4. 4. Cell Injury <ul><li>A cell maintaining a steady state called Homeostasis </li></ul>
  5. 5. Cell Injury <ul><li>Altered Homeostasis </li></ul>
  6. 6. To die or not to die? <ul><li>Integrated balance between positive survival factors and negative death signals decides fate of cell </li></ul>
  7. 8. CELL DEATH <ul><li>The 100 trillion cells of the body are members of a highly organized community </li></ul><ul><li>The total number of cells is regulated by ; </li></ul><ul><li>controlling the rate of cell division and </li></ul><ul><li>controlling the rate of cell death. </li></ul><ul><li>Cells die by one of two mechanisms </li></ul><ul><li>Necrosis or </li></ul><ul><li>Apoptosis </li></ul><ul><li>Two physiologically different processes </li></ul><ul><li>Apoptosis and necrosis have different characteristics </li></ul>
  8. 9. APOPTOSIS <ul><li>Apoptosis is an energy dependent </li></ul><ul><li>programmed cell death </li></ul><ul><li>for removal of unwanted individual cells </li></ul>
  9. 10. <ul><li>Programmed cell death during embryogenesis </li></ul><ul><li>Formation of free and independent digits </li></ul><ul><li>Development of the brain </li></ul><ul><li>Development of </li></ul><ul><li>reproductive organs </li></ul><ul><li>Programmed cell death </li></ul><ul><li>during adult stage </li></ul><ul><li>Cell loss in proliferating </li></ul><ul><li>cell populations </li></ul><ul><li>Death of cells that have served </li></ul><ul><li>their useful purpose </li></ul><ul><li>Elimination of harmful self- reacttive lymphocytes </li></ul>APOPTOSIS IN PHYSIOLOGIC SITUATIONS
  10. 11. <ul><li>Chronic viral diseases </li></ul><ul><li>Neurodegenerative diseases </li></ul><ul><li>Reperfusion injury </li></ul><ul><li>Insulin-dependent Diabetes </li></ul><ul><li>Atherosclerosis </li></ul><ul><li>Myo c ard ial Infarction </li></ul><ul><li>AIDS </li></ul><ul><li>Development and Treatment of Malignancies </li></ul><ul><li>onic viral diseases </li></ul><ul><li>... </li></ul>APOPTOSIS IN PATHOLOGICAL SITUATIONS
  11. 12. THE MECHANISMS OF APOPTOSIS <ul><li>This process involves a specific proteolytic cascade </li></ul><ul><li>There are 3 different mechanisms by which a cell commits suicide by apoptosis </li></ul><ul><li>by signals arising within the cell; </li></ul><ul><li>by death activators binding to receptors at the cell surface: </li></ul><ul><ul><li>TNF-α </li></ul></ul><ul><ul><li>Lymphotoxin </li></ul></ul><ul><ul><li>Fas ligand ( FasL ) </li></ul></ul><ul><li>third that may be triggered by dangerous reactive oxygen species. </li></ul>
  12. 13. APOPTOSIS ; MORPHOLOGIC CHANGES <ul><li>Early : Chromosome condensation, cell body shrink </li></ul><ul><li>Later : Membranes become irregular- Blebbing ; </li></ul><ul><li>Nucleus and cytoplasm fragment- Apoptotic bodies </li></ul><ul><li>At last : Phagocytosed </li></ul>
  13. 14. Membrane blebs during apoptosis
  14. 15. THE ENZYMATIC REGULATION OF APOPTOSIS <ul><li>Apoptosis is initiated by activation of a family of </li></ul><ul><li>proteases called caspases. </li></ul><ul><li>These are enzymes that are synthesized and stored in the cell as inactive procaspases. </li></ul><ul><li>once activated, the enzymes cleave and activate other procaspases, triggering a cascade that rapidly breaks down proteins within the cell </li></ul><ul><li>The cell thus dismantles itself, and its remains are rapidly digested by neighboring phagocytic cells . </li></ul>
  15. 16. <ul><li>Excessive apoptosis </li></ul><ul><li>Uncontrolled cell loss </li></ul>
  16. 17. Diseases featuring excessive apoptosis <ul><li>Neurodegenerative </li></ul><ul><ul><li>Parkinson’s disease </li></ul></ul><ul><ul><li>Alzheimer's disease </li></ul></ul><ul><ul><li>Amyotrophic lateral sclerosis (ALS) </li></ul></ul><ul><ul><li>Huntingdon’s disease </li></ul></ul>
  17. 18. <ul><li>Uncontrolled growth of cells </li></ul><ul><li>Insufficient apoptosis </li></ul>
  18. 19. Diseases featuring insufficient apoptosis <ul><li>Many cancers </li></ul><ul><li>Autoimmune Lymphoproliferative Syndrome (ALPS) </li></ul>
  19. 20. CLINICAL IMPORTANCE OF APOPTOSIS <ul><li>Recent studies suggest that abnormalities of apoptosis may play a key role in neurodegenerative diseases such as Alzheimer’s disease, as well as in cancer a nd autoimmune disorders . </li></ul><ul><li>Some drugs that have been used successfully for chemotherapy appear to induce apoptosis in cancer cells. </li></ul><ul><li>Cancer </li></ul><ul><li>Loss of the ability to undergo apoptosis leads to cancer. </li></ul>
  20. 21. NECROSIS death by injury <ul><li>cell death as the result of injury, disease, or pathological state </li></ul><ul><li>usually involves large numbers of cells. </li></ul><ul><li>Necrotic cells may spill their contents, causing inflammation and injury to neighboring cells. </li></ul>
  21. 22. COAGULATIVE NECROSIS <ul><li>Cell outlines remain intact after cell death and can be observed by light microscopy </li></ul><ul><li>is typically seen in hypoxic(low-oxygen) environments </li></ul><ul><li>Examples; </li></ul><ul><li>infarcts of solid organs, </li></ul><ul><li>heart, spleen, kidney. </li></ul>
  22. 23. CASEOUS NECROSIS <ul><li>Tissues bear soft, granular, </li></ul><ul><li>friable appearance </li></ul><ul><li>cream-cheesy(caseous) material </li></ul><ul><li>Architecture completely destroyed . </li></ul><ul><li>Examples; </li></ul><ul><li>Tuberculosis, </li></ul><ul><li>some systemic fungal infection </li></ul>A tuberculous lung with a large area of caseous necrosis
  23. 24. LIQUEFACTIVE NECROSIS (OR COLLIQUATIVE NECROSIS) <ul><li>Necrotic degradation of tissue that softens and liquify tissues grossly. </li></ul><ul><li>Examples </li></ul><ul><li>Infarction of central nervous system </li></ul><ul><li>Abscess in bacterial infection </li></ul>
  24. 25. FAT NECROSIS <ul><li>results from the action of lipases on fatty tissues </li></ul><ul><li>Chalky yellow white deposits formed </li></ul><ul><li>Basophilic calcified areas </li></ul><ul><li>Examples: </li></ul><ul><li>acute pancreatitis </li></ul><ul><li>traumatic breast tissue necrosis </li></ul>
  25. 26. FIBRINOID NECROSIS <ul><li>It is marked by deposition of fibrin-like proteinaceous material in arterial walls , </li></ul><ul><li>appears smudgy and eosinophilic on light microscopy. </li></ul><ul><li>Examples; </li></ul><ul><li>Immune vasculitis </li></ul><ul><li>Malignant hypertension </li></ul>
  26. 27. DIFFERENCE B/W APOPTOSIS AND NECROSIS <ul><li>APOPTOSIS </li></ul><ul><li>Chromatin condensation </li></ul><ul><li>• Cell shrinkage </li></ul><ul><li>• Preservation of organelles </li></ul><ul><li>and cell membranes </li></ul><ul><li>• Rapid engulfment by </li></ul><ul><li>neighboring cells </li></ul><ul><li>preventing inflammation </li></ul><ul><li>• Biochemical hallmark - </li></ul><ul><li>DNA fragmentation </li></ul><ul><li>NECROSIS </li></ul><ul><li>Nuclear swelling </li></ul><ul><li>• Cell swelling </li></ul><ul><li>• Disruption of organelles </li></ul><ul><li>• Rupture of cell and </li></ul><ul><li>Release of cellular </li></ul><ul><li>contents </li></ul><ul><li>• Inflammatory response </li></ul>
  27. 28. DIFFERENCE B/W APOPTOSIS AND NECROSIS
  28. 29. CANCER; INTRODUCTION <ul><li>Neoplasm - (new growth) abnormal mass of tissue, the growth of which exceeds and is uncoordinated with the normal tissues </li></ul><ul><li>Tumor - a non-specific term meaning lump or swelling. Often syn. for neoplasm </li></ul><ul><li>Cancer - malignant neoplasm or tumor </li></ul><ul><li>Metastasis - discontinuous spread </li></ul><ul><li>of a malignant neoplasm </li></ul><ul><li>to distant sites </li></ul>
  29. 30. Diseases featuring excessive apoptosis <ul><li>Neurodegenerative </li></ul><ul><ul><li>Parkinson’s disease </li></ul></ul><ul><ul><li>Alzheimer's disease </li></ul></ul><ul><ul><li>Amyotrophic lateral sclerosis (ALS) </li></ul></ul><ul><ul><li>Huntingdon’s disease </li></ul></ul>
  30. 31. CANCER <ul><li>Cancer is a disorder of cellular homeostasis disease in which there is uncontrolled cell division caused by: </li></ul><ul><li>by mutation </li></ul><ul><li>or by some other abnormal activation of cellular genes that control cell growth and cell mitosis . </li></ul>
  31. 32. CANCER <ul><li>The abnormal genes are called oncogenes. </li></ul><ul><li>Also present in all cells are antioncogenes , which suppress the activation of specific oncogenes. </li></ul><ul><li>Therefore, loss of or inactivation of antioncogenes can allow activation of oncogenes that lead to cancer. </li></ul><ul><li>A factor which brings about a mutation is called a mutagen. </li></ul><ul><li>Any agent that causes cancer is called a carcinogen and is described as carcinogenic. </li></ul>
  32. 33. CARCINOGENS <ul><li>Ionising radiation – X Rays, UV light </li></ul><ul><li>Chemicals – asbestos, </li></ul><ul><li>tar from cigarettes </li></ul><ul><li>Virus infection – papilloma virus can be responsible for cervical cancer. </li></ul><ul><li>Hereditary predisposition – </li></ul><ul><li>Some families are more susceptible </li></ul><ul><li>to getting certain cancers. </li></ul>carcinogen sign
  33. 34. HALLMARKS OF CANCER
  34. 35. BENIGN OR MALIGNANT? <ul><li>Benign tumours </li></ul><ul><li>do not spread from their site of origin </li></ul><ul><li>can crowd out (squash) surrounding cells </li></ul><ul><li>slow growing </li></ul><ul><li>well differentiated </li></ul>
  35. 36. <ul><li>Malignant tumours </li></ul><ul><li>can spread from the original site and cause secondary tumours . </li></ul><ul><li>This is called metastasis . </li></ul><ul><li>Fast growing </li></ul><ul><li>Poorly differentiated </li></ul><ul><li>They interfere with neighbouring cells and can block blood vessel, gut etc. </li></ul>BENIGN OR MALIGNANT?
  36. 37. GENERAL AND LOCAL EFFECTS OF CANCER <ul><li>Cancer can kill the patient by: </li></ul><ul><li>Local effects </li></ul><ul><li>Systemic effects </li></ul><ul><li>Why Do Cancer Cells Kill? </li></ul><ul><li>Cancer tissue competes with normal tissues for nutrients . </li></ul><ul><li>Because cancer cells continue to proliferate indefinitely, cancer cells soon demand essentially all the nutrition available to the body or to an essential part of the body. </li></ul><ul><li>As a result, normal tissues gradually suffer nutritive death . </li></ul>
  37. 38. REFERENCES <ul><li>Text book of medical physiology , Guyton and Hall </li></ul><ul><li>Robbins & Cotran Pathologic Basis of Disease </li></ul><ul><li>Rapid Review Pathology, By Edward F. Goljan, MD </li></ul><ul><li>http://users.rcn.com/jkimball.ma.ultranet/BiologyPages </li></ul>
  38. 39. SELF ASSESSMENT <ul><li>Q1. Is cell death necessary? why? </li></ul><ul><li>Q2. Which type of cell death is called programmed cell death? </li></ul><ul><li>Q3. Identify the processes labeled as A & B. </li></ul>A B
  39. 40. SELF ASSESSMENT <ul><li>Q4. Identify the type of necrosis in fig A& B </li></ul><ul><li>A B </li></ul>
  40. 41. <ul><li>Q5. Name some of the common carcinogens. </li></ul><ul><li>Q6. Differentiate b/w benign and malignant tumors. </li></ul>SELF ASSESSMENT

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