02-Necrosis and apoptosis-1.ppt
- 2. Objectives Define necrosis and apoptosis List the different types of necrosis, examples of each and its features List the different conditions associated with apoptosis, its morphology and its mechanism Know the difference between apoptosis and necrosis
- 3. Cell Death Death of cells occurs in two ways: 1. Necrosis--(irreversible injury) changes produced by enzymatic digestion of dead cellular elements 2. Apoptosis--vital process that helps eliminate unwanted cells--an internally programmed series of events effected by dedicated gene products
- 4. Morphology of necrosis : 1. Cellular swelling or rupture 2. Denaturation and coagulation of cytoplasmic proteins 3. Breakdown of cell organelles 4. Breakdown of nuclear DNA
- 6. Patterns of Necrosis In Tissues or Organs As a result of cell death the tissues or organs display one of these six macroscopic changes: 1. Coagulative necrosis 2. Liquifactive necrosis 3. Caseous necrosis 4. Fat necrosis 5. Gangrenous necrosis 6. Fibrinoid necrosis
- 7. Patterns of Necrosis In Tissues or Organs 1. Coagulative necrosis: The outline of the dead cells are maintained and the tissue is somewhat firm. Microscopically cell outline is preserved but there is loss of nuclei. Example: myocardial infarction 1. Liquefactive necrosis: The dead cells undergo disintegration and affected tissue is liquefied. Example: cerebral infarction.
- 8. Patterns of Necrosis In Tissues or Organs 3. Caseous necrosis: a form of coagulative necrosis (cheese-like). Example: tuberculosis lesions. 4. Fat necrosis: enzymatic digestion of fat. Example: necrosis of fat by pancreatic enzymes. 5. Gangrenous necrosis: Necrosis (secondary to ischemia) usually with superimposed infection. Example: necrosis of distal limbs, usually foot and toes in diabetes. 6. Fibrinoid necrosis: typically seen in vasculitis and glomerular autoimmune diseases
- 9. Coagulative necrosis generally occurs due to an infarct (lack of blood flow from an obstruction causing ischaemia) and can occur in all the cells of the body except the brain. The heart, kidney, adrenal glands or spleen are good examples of coagulative necrosis. Cells that undergo coagulative necrosis can become dry, hard, and white. What is interesting is that gel-like appearance occurs in dead tissues, but the architecture of the cells is maintained for at least some days. Coagulation occurs as the proteins are degraded and denatured, and an opaque film starts to form. .
- 10. Gross appearance: a pale segment may be seen in contrast to surrounding healthy tissues. The segment may be hard to the touch. Microscopic appearance: in an H&E staining tissue, eosinophilia like-cell (cells presenting pink on a histology slide) will be noticeable. Anucleated cells (cells without a nucleus) should be observable with preserved cell outlines
- 11. Coagulative necrosis Demonstrate the gross appearance of a kidney. Notice the yellow necrotic portion.
- 12. Coagulative necrosis Figure : Demonstrate the histology slide of the kidney in figure 2.The green star shows healthy cells that are less pink and have nuclei present.The blue star is a Bowman's capsule.The yellow star indicates the necrotic portion. Notice that the architectural structure of the cell is still present, but no nuclei can be seen.You could almost draw a line between damaged and non-damaged cells.
- 13. Coagulative Necrosis Changes in the cytoplasm and the nucleus Karyolysis Pyknosis Karyorrhexis
- 14. Acute renal tubular necrosis (ischemia) : increased eosinophilia and pyknosis in necrotic cells Normal Necrotic
- 15. Ischemic neuronal injury:acidophilic cytoplasm & nuclear pyknosis
- 16. … a mess - so many cells have died - the tissue is not recognizable. Nuclei have become pyknotic (shrunken and dark), undergone karorrhexis (fragmentation) and karyolysis(dissolution) Necrotic myocardium
- 17. Infarcts (vascular distribution) are wedge-shaped with a base on the organ capsule. Coagulative necrosis: is due to loss of blood supply Spleen
- 18. Depending on circumstances: 1. necrotic tissue may be walled off by scar tissue, 2. totally converted to scar tissue, 3. get destroyed (producing a cavity or cyst), 4. get infected (producing an abscess or "wet gangrene"), 5. or calcify. If the supporting tissue framework does not die, and the dead cells are of a type capable of regeneration, you may have complete healing. Remember: True coagulation necrosis involves groups of cells, and is almost always accompanied, by acute inflammation (infiltrate)
- 19. Liquefactive necrosis e can be associated from bacterial, viruses, parasites or fungal infections. Unlike coagulative necrosis, liquefactive necrosis forms a viscous liquid mass as the dead cells are being digested. The micro-organisms can release enzymes to degrade cells and initiate an immune and inflammatory response. Cellular dissolution and digestion of dying cells may also release further enzymes, which speeds up the liquefying process. bacterial hydrolytic enzymes or lysosomal hydrolytic enzymes. These are proteases (collagenases, elastases), DNases and lysosomal enzymes. .
- 20. A creamy yellow liquid should be present as lots of leukocytes are found to be dead, this is generally called pus. an infarct that involves the nervous system (such as the brain) should present as coagulative necrosis but does not occur, instead liquefactive necrosis is present.
- 21. Gross appearance: liquid-like layer can be seen; pus should be present.Yellowing, softening or swelling of the tissue should be seen. Malacia (softening, or loss of consistency) should be present. A cystic space should be present for tissue resolution. Microscopic appearance: macrophages and neutrophils, both dead and alive, should be present. Debris and lysed cells should be seen with inflammation. Partial space should be filled with lipids and debris.There is a loss of neurons and glial cells, with the formation of clear space
- 22. LIQUEFACTIVE NECROSIS Characterized by digestion of dead cells resulting in transformation of the tissue into a liquid viscous mass Is characteristic of focal bacterial , or occasional fungal infections because microbes stimulate the accumulation of inflammatory cells E.g. hypoxic death in central nervous system If the process is initiated by acute inflammation, the material is creamy yellow because of the presence of dead white cells called pus
- 23. Liquefactive Necrosis Rate of dissolution of the necrotic cells is faster than the rate of repair. Usually results in an abscess secondary to bacterial infection. Liquefactive necrosis : hydrolysis of dead tissues or cells (rapidly destroyed by lysosomal enzymes from neutrophilic leukocytes (i.e., bacterial infections), or clostridia or snake poison. Liquefactive necrosis that is caused by neurophilic leukocytes is called pus.
- 24. Liquefactive necrosis: two lung abscesses Removal of the dead tissue leaves behind a cavity or scar
- 25. Localized liquefactive necrosis liver abscess Removal of the dead tissue leaves behind a scar
- 26. Cerebral infarction - this will liquefy eventualy
- 27. Liquefactive necrosis in the brain: in a patient suffered a "stroke"
- 28. Liquefactive necrosis of the brain: macrophages cleaning up the necrotic cellular debris Removal of the dead tissue leaves behind a cavity
- 29. Liquefactive necrosis in brain leads to resolution with cystic spaces.
- 30. Fat Necrosis Specific to adipose tissue with triglycerides. With enzymatic destruction(lipases) of cells, fatty acids are precipitated as calcium soaps. Grossly- chalky white deposits in the tissue. Microscopically –. basophilic (bluish) calcium deposits are present. Anucleated adipocytes with a cytoplasm that is more pink and contains amorphous mass of necrotic material. Inflammation would be present
- 31. Fat necrosis secondary to acute pancreatitis
- 32. Microscopically, fat necrosis adjacent to the pancreas is seen here. There are some remaining steatocytes at the left which are not necrotic, as seen as a green star.The necrotic fat cells at the right have vague cellular outlines, have lost their peripheral nuclei, and their cytoplasm has become a pink amorphous mass of necrotic material, as seen as a yellow star.
- 33. Caseous necrosis: A form of coagulative necrosis but appear cheese-like Example: tuberculosis lesions fungal infections Coccidioidomycosis blastomycosis histoplasmosis
- 34. CASEOUS NECROSIS Distinctive form of coagulative necrosis most often encountered in tuberculous infection The term caseous is derived from cheesy white gross appearance of area of necrosis which is friable and white Microscopic appearance Necrotic focus – collection of fragmented or lysed cells and amorphous granular debris enclosed with in distinctive inflammatory border – granulomatous reaction
- 35. Caseous necrosis in a hilar pulmonary lymp node infected with tuberculosis.
- 36. Caseous necrosis: confluent cheesy tan granulomas in the lung in a patient with tuberculosis
- 37. Caseous necrosis: confluent cheesy tan granulomas in the lung in a patient with tuberculosis. This is characteristic of a poorly - understood subtype of immune injury, seen in certain granulomatous diseases (tuberculosis and certain fungal infections (coccidioidomycosis, blastomycosis and histoplasmosis) The macrophage-derived protein tumor-necrosis factor alpha ("cachectin") is the principal toxin that causes cells to undergo caseous necrosis
- 38. Pulmonary tuberculosis:tubercle contains amorphous finely granular, caseous ('cheesy') material typical of caseous necrosis. Removal of the dead tissue leaves behind a scar
- 39. Caseous necrosis is characterized by acellular pink areas of necrosis, surrounded by a granulomatous inflammatory process. N
- 40. Gangrenous necrosis Necrosis (secondary to ischemia) usually with superimposed infection. Example: necrosis of distal limbs, usually foot and toes in diabetes
- 41. Types of the gangrenes Dry gangrene – dead necrotised tissue remains uninfected. Wet gangrene-necrotic tissue becomes infected Gas gangrene – Wet gangrene infected by one of the gas forming Clostridia
- 42. Dry gangrene Gangrene begins in distal part of limb due to ischemia Causes- Atherosclerosis of anteries supplying limb Thromboangitis obliterans Raynauds disease Trauma Ergot poisoning
- 43. Due to ischemia tissues undergoes infarction and line of separation is formed between the necrotic tissue and healthy tissue. At the margins of necrotic tissue, granulation tissue develops Morphology Grossly the affected part is dry shrunken and dark in colour resembling the mummified foot Black colour is due to release of haemoglobin from the haemolysed RBC’s which are acted upon by the hydrogen disulfide produced by bacteria which results in the formation of black iron sulphide Gradually the gangrenous tissue falls from the healthy tissue at the line of separation Because of the risk of infection it should be surgically separated
- 44. “Wet" gangrene “ of the lower extremity in patient with diabetes mellitus: 1. liquefactive component from superimposed infection or 2. coagulative necrosis from loss of blood supply.
- 45. Gas gangrene It is wet gangrene infected by one of the gas forming Clostridia (Gram positive anaerobic bacteria) Gas forming Clostridia enters the tissue through a contaminated wound or as a complication of operation on colon which normally contains Clostridia Clostridia rapidly spreads through tissues especially in muscles and cause extensive necrosis and massive edema
- 46. Morphology Gross – the affected part is edematous, swollen and has crepitations on palpation due to accumulation of gas in tissues Microscopically Muscle fibres undergo coagulative necrosis with liquefaction At the periphery, a zone of leukocytic infiltration, oedema and congestion are found
- 47. FIBRINOID NECROSIS Special form of necrosis seen in immune reactions involving blood vessels Occurs when complexes of antigens and antibodies are deposited in the walls of arteries Along with these complexes fibrin which has leaked out of vessels give bright pink amorphous appearance called fibrinoid (Fibrin like
- 48. Demonstrates gangrene of the lower extremity. In this case, the term "wet" gangrene is more applicable because of the liquefactive component from superimposed infection in addition to the coagulative necrosis from loss of blood supply. Demonstrates gangrene, or necrosis of many tissues in a body part. In this case, the toes were involved in a frostbite injury.This is an example of "dry" gangrene in which there is mainly coagulative necrosis
- 49. Fibrinoid necrosis: afferent arteriole and part of the glomerulus are infiltrated with fibrin, (bright red amorphous material)
- 50. Fibrinoid necrosis of artery
- 51. Objectives Define necrosis and apoptosis List the different types of necrosis, examples of each and its features List the different conditions associated with apoptosis, its morphology and its mechanism Know the difference between apoptosis and necrosis
- 52. Cell Death Apoptosis • vital process that helps eliminate unwanted cells • an internally programmed series of events effected by dedicated gene products
- 53. Apoptosis Physiologic process to die This process helps to eliminate unwanted cells by an internally programmed series of events effected by dedicated gene products. It serves several vital functions and is seen under various settings. Remember: apoptosis require energy to die
- 54. Apoptosis SEEN IN THE FOLLOWING CONDITIONS: A. Physiologic 1. During development for removal of excess cells during embryogenesis 2. To maintain cell population in tissues with high turnover of cells, such as skin, bowels. 3. To eliminate immune cells after cytokine depletion, and autoreactive T-cells in developing thymus. 4. Hormone-dependent involution - Endometrium, ovary, breasts etc.
- 55. Apoptosis SEEN IN THE FOLLOWING CONDITIONS: B. Pathologic 1. To remove damaged cells by virus 2. To eliminate cells after DNA damage by radiation, cytotoxic agents etc. 3. Cell death in tumors.
- 56. Morphology of Apoptosis 1. Shrinkage of cells 2. Condensation of nuclear chormatin peripherally under nuclear membrane 3. Formation of apoptotic bodies by fragmentation of the cells and nuclei. The fragments remain membrane-bound and contain cell organelles with or without nuclear fragments. 4. Phagocytosis of apoptotic bodies by adjacent healthy cells or phagocytes. 5. Unlike necrosis, apoptosis is not accompanied by inflammatory reaction
- 57. Apoptosis: liver cells are dying individually from injury by viral hepatitis.
- 58. Liver biopsy - viral hepatitis: acidophilic body (councilman body) (apoptosis, i.e., induced, or programmed, individual cell death). Vacuolar change is reversible.
- 60. MECHANISMS OF APOPTOSIS 1. Cause of chromatin condensation is internucleosomal DNA fragmentation mediated by calcium-sensitive endonuclease. 2. Alteration in cell volume due to action of transglutaminase. 3. Phagocytosis of apoptotic bodies is mediated by receptors on the macrophages. 4. Apoptosis is dependent on gene activation and new protein synthesis, e.g. bcl-2, c-myc oncogene and p53.
- 61. apoptosis . Occurs more frequently, involves one cell at a time, localised. Controlled program of cell death. Contains intrinsic and extrinsic pathways. Caspase dependent pathway. Inflammation absent. Cell shrinks in size and the condensation of chromatin occur. No leakage and no release of enzymes as small blebs are being released. Hence no damage to surrounding tissues. Intact plasma membrane structure. Eosinophilia cell-like not present (cells presenting pink on a histology slide). Nuclear changes: fragments into nucleosome-size fragments or the nucleus usually dissolves into apoptotic bodies. Karyorrhexis and pyknosis.
- 62. necrosis Occurs less frequently, involves many cells, may not be localised and is pathological. Abnormal and uncontrolled cell death that is associated with a pathological condition. Caused by external and internal injuries. Caspase independent pathway. Inflammation present. Cell swells and burst, releasing its content at once. Swelling of the mitochondria and endoplasmic reticulum occurs. Leakage and enzymatic digestion of neighbouring cellular contents. Disrupted plasma membrane structure. Eosinophilia cell-like present (cells presenting pink on a histology slide). Nuclear changes: pyknosis, karyorrhexis and karyolysis.
- 63. Genes that regulate apoptosis: Oncogene Bcl-2 Bcl-2 overexpression prevents apoptosis Antagonized by cell death (ced) genes & others (bax,bad) Localized to mitochondria, nuclear envelope and ER Tumor suppresor gene p-53 Will cause cells with DNA damage (eg amplified myc) to go apoptosis Induce bax expression Reversed by overexpression of bcl-2