Cell injury 2


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Cell injury 2

  1. 1. Reversible Injury Irreversible Injury Severe mitochondrial Swelling with Few smallMitochondria( 1 membrane swollen & Large . amorphous densities amorphous densities Intact with few Extensive damage to plasmaPlasma( 2 Blebbing, Blunting, with membrane with loss cellularMembrane loss of microvillus .organelle Membrane damaged withLysosome( 3 Membrane intact .vacuoles Smoothening withEndoplasmic( 4 Lysis of ER with dilatation detachments ofReticulum .with detachment of ribosome .ribosome Pyknosis->Karyorrhexis-Nucleus( 5 Clumping of chromatin .>Karyolysis Eosinophilic with Fine Shows Course Myelin figureCytoplasm( 6 Myelin figure
  2. 2. Cell swelling - Light Microscopy Cellular Swelling= hydropic change Normal epithelium
  3. 3. Nuclear Pyknosis Karyorrhexis Karyolysis
  4. 4. Necrosis Necrosis refers to a spectrum of morphologicchanges that follow cell death in living tissue,largely resulting from the progressivedegradative action of enzymes on the lethallyinjured cell occurs in the irreversible exogenous injury Causes inflammation in the surrounding tissueas leakage of cellular organelle from damagedcell membrane occurs. occurs
  5. 5. Morphology of NecrosisCytoplasm: increased eosinophilia because of the normal basophiliaimparted by the RNA in the cytoplasm because of increased bindingof eosin to denatured Intracytoplasmic proteins the cytoplasm becomes vacuolated and appears moth-eaten. Calcification of the dead cells. Dead cells ultimately replaced bylarge, whorled phospholipids masses called myelin figuresNuclear: Pyknosis characterized by nuclear shrinkage and increasedbasophilia. the DNA apparently condenses into a solid, shrunkenbasophilic mass. Karyolysis basophilia of the chromatin may fade. Karyorrhexis pyknotic nucleus undergoes fragmentation.With the passage of time in a day or two, the nucleus in thenecrotic cell totally disappears.
  6. 6. By electron microscopyNecrotic cells are characterized by1 , Damaged plasma and organelle membranes Marked dilation of mitochondria with the appearance of2 , large amorphous densities3 ,Intracytoplasmic myelin figures4 ,Amorphous osmiophilic debris Aggregates of fluffy material probably representing5 denatured protein
  7. 7. Types of Necrosis : Coagulative Necrosis , Liquifactive Necrosis, Gangrenous Necrosis, Caseous Necrosis, Fat Necrosis. Fibrinoid Necrosis.
  8. 8. 1) Coagulative Necrosis : • Preservation of the basic outline of the coagulated cell for a span of at least some days. • Affected tissues exhibit a firm texture, • Preservation of the general tissue architecture, is characteristic of hypoxic death of cells in all tissues except the brain.A wedge-shaped kidney infarct (yellow). B, Microscopic view of the edge ofthe infarct, with normal kidney (N) and necrotic cells in the infarct (I) showingpreserved cellular outlines with loss of nuclei and an inflammatory infiltrate
  9. 9. 2) Liquefactive Necrosis :• Charestic of focal bacterial or fungal infection.• Often seen in hypoxic death of CNS.• liquefaction completely digests the dead cells.• The end result is transformation of the tissue into aliquid viscous mass. • If the process was initiated by acute inflammation, the material is frequently creamy yellow because of the presence of dead white cells and is called pus.
  10. 10. 3) Gangrenous Necrosis (Surgical term):• Generally the lower leg, that has lost its blood supplyand has undergone coagulation necrosis. When bacterialinfection is superimposed, Coagulative necrosis ismodified by the liquefactive action of the bacteria and theattracted leukocytes (so-called wet gangrene).• Dry gangrene: Is a form of infarction that results fromischemia and when there is secondary no infection becauseit gets dry. Characterized primarily by Coagulativenecrosis without liquefaction. Dead tissue has mummifiedappearance (e.g. diabetic foot). Wet gangrene Dry gangrene
  11. 11. 4) Caseous Necrosis :• A distinctive form of Coagulative necrosis, seen in tuberculousinfection .The term caseous is derived from the cheesy white grossappearance of the area of necrosis.•On M/E: the necrotic focus appears as amorphous granular debrisseemingly composed of fragmented, coagulated cells andamorphous granular debris enclosed within a distinctiveinflammatory border known as a granulomatous reaction Epitheli oid cell Langha n’s giantA tuberculous lung with a large cellarea of caseous necrosis. Thecaseous debris is yellow-white andcheesy.
  12. 12. 5) Fat Necrosis :•This occurs in acute pancreatitis , activated pancreaticenzymes escape from acinar cells and ducts, the activatedenzymes liquefy fat cell membranes.• Activated lipases split the triglyceride esters contained withinfat cells. The released fatty acids combine with calcium toproduce grossly visible chalky white areas as fat saponification. saponification• On M/E, the necrosis takes the form of foci of shadowyoutlines of necrotic fat cells, with basophilic calcium deposits,surrounded by an inflammatory reaction. fat cells have lost their peripheral nuclei and their cytoplasm has converted to a mass of basophilic amorphous necrotic material.
  13. 13. 6) Fibrinoid Necrosis :• Usually seen in immune reactions involving blood vessels.• This pattern of necrosis typically occurs when complexes ofantigens and antibodies are deposited in the walls of arteries.• Deposits of these “immunecomplexes,” together withfibrin that has leaked out ofvessels, result in a brightpink and amorphousappearance in H&E stains,called “fibrinoid” seen invasculitis syndromes
  14. 14. Apoptosis• From Greek meaning falling off.• Programmed and genetically controlled, enzyme dependent, specialized form of death of individual cells.• An active process and involves RNA and protein synthesis.• Plays role in – Physiologic cell death – Pathologic cell death.• Different from necrosis.
  15. 15. Apoptosis Apoptosis is a pathway of cell death that is inducedby a tightly regulated suicide program in which cells dieby activating enzymes that degrade the cells ownnuclear DNA and nuclear and cytoplasmic proteins. Apoptotic cells break up into fragments, calledapoptotic bodies, which contain portions of the cytoplasmand nucleus. The plasma membrane of the apoptotic celland bodies remains intact. Death by apoptosis is a normal phenomenon thatserves to eliminate cells that are no longer needed, and tomaintain a steady number of various cell populations intissues.
  16. 16. Remember !IN APOPTOSIS:•Cells actually expend energy in order to die.•The cell membrane does not rupture.•The cell contents are not released into theextracellular space, and•Inflammation does not occur.
  17. 17. Physiologic examples of apoptosis1. Embryogenesis • Disappearance of Mullerian and Wolffian duct structures. • Development of lumen within hollow organs (e.g bowel and heart).1. Hormone-dependent involution in adults – Endometrial breakdown in menstruation. – Post-lactational atrophy of breast. – Prostate atrophy following castration.1. Involution of Thymus in the adult.2. Cells that are programmed to die; for example, 1. The cells of the outer layers of epidermis, 2. Cells in the gut epithelium.
  18. 18. Apoptosis in Physiologic Situations Embryogenesis: programmed destruction of cellsHormone-dependent involution in the adult, such asendometrial cell breakdown during the menstrual cycle, the regressionof the lactating breast after weaning, and prostatic atrophy aftercastration. Cell deletion in proliferating cell populations ( intestinalepithelia). Death of host cells that have served their useful purpose, such asneutrophils in an acute inflammatory response, and lymphocytes at theend of an immune response. Elimination of potentially harmful self-reactivelymphocytes, either before or after they have completed theirmaturation Cell death induced by cytotoxic T cells, a defense mechanismagainst viruses and tumors that serves to eliminate virus-infected andneoplastic cells.
  19. 19. Apoptosis in Pathological conditionsApoptosis eliminates cells that are injured beyond repair withouteliciting a host reaction.DNA damage. Radiation, cytotoxic anticancer drugs, and hypoxia candamage DNA, either directly or via production of free radicals. These injuriousstimuli can cause apoptosis if the insult is mild. The damaged DNA, which mayresult in malignant transformation.Accumulation of misfolded proteins mutations in the genes encoding theseproteins or because of extrinsic factors, such as damage caused by free radicals.Excessive accumulation of these proteins in the ER leads to a condition called ERstress, which culminates in apoptotic cell death.Cell death in certain in viral infections, (in Adenovirus and HIV infections) infectionsor by the host immune response (as in viral hepatitis). An important hostresponse to viruses consists of cytotoxic T lymphocytes specific for viral proteins isresponsible for cell death in viral, tumors and cellular rejection of transplants.Pathologic atrophy in parenchymal organs after duct obstruction , such asoccurs in the pancreas, parotid gland, and kidney.
  20. 20. Morphologic appearance1. Apoptotic cells: 1. Have deeply pink staining cytoplasm. 2. Have pyknotic nucleus which fragment. 3. Are smaller in size. 4. Breakdown into fragments (apoptotic bodies). 5. Phagocytosis of apoptotic bodies by adjacent cells or macrophages. 6. A lack of inflammatory response.
  21. 21. Removal of dead cells• Formation of cytoplasmic buds on the cell membrane containing – Nuclear fragments, mitochondria and protein fragments.• Breaking off of cytoplasmic buds  apoptotic bodies.• Phagocytosis of apoptotic bodies by neighboring cells or macrophages.
  22. 22. Reversible cell InjuryIrreversible cell Injury
  23. 23. Apoptosis of Apoptotic cell in epidermal liver cells
  24. 24. Studies that the most effective way of prolonging life span is• Calorie restriction. effect of calorie restriction on longevityappears to be mediated by a family of proteins called sirtuins.•Sirtuins have histone deacetylase activity, reduceapoptosis, stimulate protein folding, and inhibit the harmfuleffects of oxygen free radicals. Sirtuins also increase insulinsensitivity and glucose metabolism. Food product like Vit-C,Vit-A, Vit-D, Green Tea, B-Carotiens and Red wine activatesirtuins and thus increase life span Or decreases Cellular Aging!• Growth factors, such as insulin-like growth factor, andintracellular signaling pathways triggered by these hormones alsoinfluence life span.• Transcription factors activated by insulin receptorsignaling may induce genes that reduce longevity, and insulinreceptor mutations are associated with increased lifespan.