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JAYUS INASTIAWAN

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  • JAYUS INASTIAWAN

  • Page *

    Please mute Your cell!

  • Page *JEJAS SELSel merupakan partisipan aktif di lingkungannya, yg secara tetap menyesuaikan struktur & fungsinya untuk mengakomodasi tuntutan perubahan dan stres ekstrasel.Sel cenderung mempertahankan lingkungan segera dan intraselnya dalam rentang parameter fisiologis yang relatif sempit --- sel mempertahankan homeostasis normal.

  • KERUSAKAN SELCIDERA SEL / INJURY SELCidera reversible : cidera yg relative ringan dan kemungkinan sel kembali ke dalam bentuk semula Cidera irreversible, bila sel mati (cell death/apoptosis cellSel yang cidera tp tidak mati akan mengalami DEGENERASI yaitu perubahan morfologi / bentuk sel akibat kerusakan yang tidak fatal / reversibel.

  • *FIGURE 11 Stages of the cellular response to stress and injurious stimuli.

  • BENTUK-BENTUK PERUBAHAN DEGENERATIFDegenerasi bengkak keruh / Pembengkakan sel / cloudy swelling yaitu terjadinya penimbunan air di dalam sel-sel yang rusak (tp mrp kerusakan ringan).

    Secara makroskopis : terlihat pembesaran jaringan / organ yang terkena, dapat dideteksi dgn peningkatan sedikit BB.Perubahan / degenerasi hidropik / degenerasi vacuoler. Secara mikroskopis terlihat sitoplasma sel yang bervakuola (terdapat kantong-kantong yg berisi air pada RE), disebabkan oleh kegagalan pompa Na/K di dlm membran sel

  • Degenerasi lemak / infiltrasi lemak / steatosis / perlemakan hati, yaitu Penimbunan lipid didalam sel-sel yang rusak. Biasanya terjadi pada ginjal, jantung dan hati. (= hidropik, tapi isi vakuola adalah lipid bukan air).

    Secara makroskopis perubahan pada jaringan yg terkena meliputi pembengkakan jar, penambahan berat pada organ2 yg terkena, dan terlihat silinder berwarna kekuningan pada jaringan akibat adanya kandungan lipidPerlemakan hati dapat ditemukan pada pasien dgn malnutrisi, makan berlebihan, hipoksia, dan alkoholis

  • KEMATIAN SELJika pengaruh buruk pada sebuah sel cukup hebat atau terus berlangsung cukup lama, maka sel akan mencapai suatu titik dimana tidak lagi dapat mengompensasi dan tidak dapat melanjutkan metabolisme, proses tersebut menjadi irreversible, dan sel akan mati / NEKROSISJika sel yg telah mati masih tetap tinggal di dlm hospes, akan terjadi hal-hal brkt:Sewaktu sel hidup enzim-enzim yg terkandung didalam sel (umumnya litik) tidak menimbulkan kerusakan pada sel, tp enzim2 ini dilepaskan pada saat sel mati dan mulai melarutkan berbagai unsur selulerPada saat sel mati, terjadi perubahan secara kimiawi, jaringan hidup yg tepat disebelahnya memberikan respon terhadap perubahan itu dan menimbulkan reaksi peradangan akut dimana terjadinya pengiriman leukosit ke daerah tsb yg membantu pencernaan sel-sel yg sudah mati

  • APOPTOSIS : kematian sel yang terprogramBentuk kematian sel ini diprogram oleh informasi genetik yg telah ada di dalam sel, melibatkan sel-sel tunggal atau kelompok bbrp sel, dan bila sel tsb mati, akan membentuk fragmen mjd potongan-potongan yg terikat membran yg dgn cepat difagositosis oleh sel disebelahnya / oleh makrofagApoptosis diperlukan untuk:Pembentukan jari-jari tangan dan kaki pada janin meliputi pembuangan oleh apoptosis pada jaringan diantara jari-jari tsbPengelupasan endometrium pada saat awal menstruasi terjadi akibat apoptosis

  • Pembentukan hubungan yang sesuai (sinaps) diantara neuron didalam otak memerlukan penghilangan kelebihan sel oleh apoptosisKematian sel yg terprogram jg diperlukan untuk menghancurkan sel-sel yg merupakan ancaman bagi integritas organisme, spt:Sel-sel terinfeksi oleh virusSel-sel dgn kerusakan DNASel-sel sistem imunSel-sel kanker

  • Apoptosis merupakan bagian pusat perkembangan normal, berbeda dgn nekrosis, yg tidak tdp pada perkembangan normal dan merupakan respons terhadap cedera atau kerusakan toksik. Apoptosis secara khas mengenai sel-sel individu yg tersebar dan tidak mengakibatkan peradangan, berbeda dengan nekrosis yg biasanya mengenai jalur-jalur sel-sel disebelahnya dengan daerah yg dikelilingi oleh peradangan

  • Swollen kidney tubulesIncreased eosinophilic stainingDecreased basophilic staining (RNA) Plasma membrane rounding, blebbing, loss of cilia, due to loss of connections with cytoskeletonIntegrity of tubules degrading, but basement membranes intactNuclei largely intact, slightly narrowed, pyknotic

    *B, Early (reversible) ischemic injury showing surface blebs, increased eosinophilia of cytoplasm, and swelling of occasional cells.

  • Necrotic kidney tubulesCellular fragmentationLoss and fading of nuclei--karyolysisBurst membranesLoss of tissue architecture

    * C, Necrosis (irreversible injury) of epithelial cells, with loss of nuclei, fragmentation of cells, and leakage of contents. The ultra structural features of these stages of cell injury are shown in Figure 110. (Courtesy of Drs. Neal Pinckard and M.A. Venkatachalam, University of Texas Health Sciences Center, San Antonio, TX.)

  • *FIGURE 2025 Acute kidney injury. Some of the tubular epithelial cells in the tubules are necrotic, and many have become detached (from their basement membranes) and been sloughed into the tubular lumens, whereas others are swollen, vacuolated, and regenerating. (Courtesy of Dr. Agnes Fogo, Vanderbilt University, Nashville, TN.)

    Look to see where the patterns emerge, starting with one of the two well-defined tubules. Swollen cells will have clear areas of vacuolarization due to ER smoothing, dilation, pinching. Necrotic cells are more eosinophilic (deeper pink) due to accumulation of denatured proteins and loss of RNA. Dead cells without nuclei are sloughed into tubular lumen. Dying cells have either fading, karyolytic nuclei; or condensed, pyknotic nuclei.

  • Tissue necrosisCoagulative necrosisProteins denature and aggregate rather than degradeDry gangreneLiquefactive necrosisEnzymatic digestion of cellular componentsWet gangreneCaseous necrosisEnd result of tuberculous infections, granulomaFatty necrosisEnd result of pancreatic lipases digesting fat cells resulting in calcium soapsFibrinoid necrosisAg-Ab complexes and fibrin accumulate in arteries or other vessels

  • Coagulative necrosisCellular proteins denature (unstick and unwind) due to altered osmotic environment and acidosisAnuclear cells stain more deeply pink, tissue retains gross architectureCells burst and are cleared by phagocytesResults from hypoxia in tissues other than brain (which liquifies instead)

  • Coagulative necrosismyocardial infarctionWhen there is marked cellular injury, there is cell death and necrosis. This microscopic appearance of myocardium shown here is a mess because so many cells have died that the tissue is not recognizable. Many nuclei have become pyknotic (shrunken and dark) and have then undergone karyorrhexis (fragmentation) and karyolysis (dissolution). The cytoplasm and cell borders are no longer recognizable. In this case, loss of the blood supply from a major coronary artery led to ischemia and cell death.

    *http://library.med.utah.edu/WebPath/CINJHTML/CINJ012.html

    Although the structure of the tissue is no longer recognizable, there are some dense, eosinophilic areas, and there are no large pools of pus or aqueous, hydrolytic areas. This is not yet, then, liquefactive necrosis.

  • Coagulative necrosismyocardial infarctionHere is myocardium in which the cells are dying as a result of ischemic injury from coronary artery occlusion. This is early in the process of necrosis. The nuclei of the myocardial fibers are being lost. The cytoplasm is losing its structure, because no well-defined cross-striations are seen.

    *http://library.med.utah.edu/WebPath/CINJHTML/CINJ013.html

    These cells still clearly resemble muscle.

  • Coagulative necrosismyocardial infarctionGross, cross section: A pale, whitish infarct is surrounded by a zone of hyperemia (vascular dilatation).

    Very low power glass slide: The area of coagulative necrosis is bright pink compared to the lighter pink viable myocardium. The bluish areas on each side of the necrotic zone represent the granulation tissue response to the necrosis.

    *ExpertConsult > Case Studies > Begin > Cell Injury > Introductory Images > Image 11 and 12

  • *The small intestine is infarcted. The dark red to grey infarcted bowel contrasts with the pale pink normal bowel at the bottom. Some organs such as bowel with anastomosing blood supplies, or liver with a dual blood suppy, are hard to infarct. This bowel was caught in a hernia and the mesenteric blood supply was constricted by the small opening to the hernia sac. http://library.med.utah.edu/WebPath/CINJHTML/CINJ019.html

    GRIPE Image: 234 Item: 72-41-003-1 Organ/System: Small Intestine Diagnosis: infarct Description: coagulation necrosis transmural, submucosal edema, marked vascular congestion

  • Coagulative necrosiskidney infarctionThis is the typical pattern with ischemia and infarction (loss of blood supply and resultant tissue anoxia). Here, there is a wedge-shaped pale area of coagulative necrosis (infarction) in the renal cortex of the kidney. Microscopically, the renal cortex has undergone anoxic injury at the left so that the cells appear pale and ghost-like. There is a hemorrhagic zone in the middle where the cells are dying or have not quite died, and then normal renal parenchyma at the far right.

    *http://library.med.utah.edu/WebPath/CINJHTML/CINJ015.htmlhttp://library.med.utah.edu/WebPath/CINJHTML/CINJ016.html

  • *Gangrenous necrosis involves the tissues of a body part. The inflammation seen here is extending beneath the skin of a toe to involve soft tissue (fat and connective tissue) and bone. Because multiple tissues are non-viable, amputation of such areas is necessary. WebPath/CINJHTML/CINJ051.html

    GRIPE Images 923, 924

  • Liquefactive necrosisEnzymatic digestion of cellular componentsInfiltration of leukocytes and neutrophils create pus and contribute to hydrolysis of tissueGross tissue architecture lost to degradation of connective tissueServes as substrate for bacterial or fungal growth, sepsis, leading to wet gangreneHypoxic brain injury (infarctions) typically result in dissolution and liquefication without sepsis, due to high fat content and lack of collagenous connective tissue

  • Liquefactive necrosis

    *The liver shows a small abscess here filled with many neutrophils. This abscess is an example of localized liquefactive necrosis. This is liquefactive necrosis in the brain in a patient who suffered a "stroke" with focal loss of blood supply to a portion of cerebrum. This type of infarction is marked by loss of neurons and neuroglial cells and the formation of a clear space at the center left. As this infarct in the brain is organizing and being resolved, the liquefactive necrosis leads to resolution with cystic spaces.http://library.med.utah.edu/WebPath/CINJHTML/CINJ021.htmlhttp://library.med.utah.edu/WebPath/CINJHTML/CINJ022.html http://library.med.utah.edu/WebPath/CINJHTML/CINJ025.html

  • Other necrosesCaseous necrosisEnd result of tuberculous infections, granulomaFatty necrosisEnd result of pancreatic lipases digesting fat cells resulting in calcium soapsFibrinoid necrosisAg-Ab complexes and fibrin accumulate in arteries or other vessels

    *These are limited-use terms that are applied to specific damage in certain tissues, whereas nearly all tissues exhibit coagulative necrosis.

  • Caseous necrosis of lung

    *This is the gross appearance of caseous necrosis in a hilar lymph node infected with tuberculosis. The node has a cheesy tan to white appearance. Caseous necrosis is really just a combination of coagulative and liquefactive necrosis that is most characteristic of granulomatous inflammation. This is more extensive caseous necrosis, with confluent cheesy tan granulomas in the upper portion of this lung in a patient with tuberculosis. The tissue destruction is so extensive that there are areas of cavitation (cystic spaces) being formed as the necrotic (mainly liquefied) debris drains out via the bronchi. Microscopically, caseous necrosis is characterized by acellular pink areas of necrosis, as seen here at the upper right, surrounded by a granulomatous inflammatory process. http://library.med.utah.edu/WebPath/CINJHTML/CINJ028.htmlhttp://library.med.utah.edu/WebPath/CINJHTML/CINJ029.htmlhttp://library.med.utah.edu/WebPath/CINJHTML/CINJ030.html

  • Cellular injury to the pancreatic acini leads to release of powerful enzymes which damage fat by the production of soaps, the chalky white areas seen here on the cut surfaces. Microscopically, 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. There are some remaining steatocytes at the left which are not necrotic.

    *http://library.med.utah.edu/WebPath/CINJHTML/CINJ026.htmlhttp://library.med.utah.edu/WebPath/CINJHTML/CINJ027.html

  • Fibrinoid necrosis of vessels

    *Image: 633Item: 62-40-003-2Diagnosis: acute necrotizing arteritisDescription: high power, small artery with mural edema, fibrinoid necrosishttp://peir.path.uab.edu:3555/images/med/00010628.jpgImage: 628Item: 62-40-008-2Topic: VESSELS : VasculitidesOrgan/System: MuscleDiagnosis: polyarteritisDescription: low power, angular atrophic fibers, small fibrotic artery with fibrinoid necrosis

  • Mechanisms leading to necrotic cells

  • Energy depletionInhibition of oxidative phosphorylationIschemia, mitochondrial damage, toxins[ATP] decreasesSmall changes, 5 - 10%, are sufficient to limit the Na/K-ATPase and Ca/Mg ATPaseGlycolytic capacity (glycogen stores) protects from ATP depletion but leads to acidificationPlasma and ER membranes swellEnzyme kinetics change; proteins begin to denatureChromatin clumpsDenatured proteins either coagulate resulting in necrosis or bind HSPs triggering apoptosis

  • *FIGURE 117 Functional and morphologic consequences of decreased intracellular ATP during cell injury. The morphologic changes shown here are indicative of reversible cell injury. Further depletion of ATP results in cell death, typically by necrosis. ER, endoplasmic reticulum.

  • Calcium influxIntracellular, cytosolic [Ca++] as many as 4 orders of magnitude lower than extracellular or organellar (ER, SR, Mt)Mictochondrial damage and ER swelling releases Ca++ to cytosolHydrolytic enzymes activatedApoptosis may be activatedNecrosis occurs

  • *FIGURE 119 The role of increased cytosolic calcium in cell injury. ER, endoplasmic reticulum.

  • ROS and free radicalsHydroxyl radicals and hydrogen may be split from water by ionizing radiationSuperoxide radicals, hydrogen peroxide, lipid peroxides normally present in small amountsNeutralized by catalase or glutathione peroxidaseROS created and released by neutrophils in response to microbial infectionToxic chemicals natively, or after activation by P450 redox in liver or kidney, may result in free radicalsROS initiate chain reaction of lipid peroxidation in membranes

  • *FIGURE 120 The role of reactive oxygen species (ROS) in cell injury. O2 is converted to superoxide () by oxidative enzymes in the endoplasmic reticulum (ER), mitochondria, plasma membrane, peroxisomes, and cytosol. is converted to H2O2 by dismutation and thence to OH by the Cu2+/Fe2+-catalyzed Fenton reaction. H2O2 is also derived directly from oxidases in peroxisomes (not shown). Resultant free radical damage to lipids (by peroxidation), proteins, and DNA leads to injury to numerous cellular components. The major antioxidant enzymes are superoxide dismutase (SOD), glutathione peroxidase, and catalase

  • ApoptosisProgrammed cell deathEspecially during fetal developmentIn response to hormonal cycles (e.g. endometrium)Normal turnover in proliferating tissues (e.g. intestinal epithelium)Cells shrink, not swellNuclei condense and DNA fragmentsCells fragment into membrane-bound bitsBits are phagocytosed by macrophages

  • Apoptosismitochondrial activationInitiated by cellular damage or viral infectionMitochondrial membrane permeability regulated by Bcl-2, Bcl-x, Mcl-1 Activated by BH3-only proteins which create Bax/Bak channelsCytochrome C released to cytosolCytC binds Apaf-1and activates caspase-9Caspases (cysteine proteases that cleave after aspartate residues) activate a cascade of lytic enzymesCellular and nucleosomal fragmentation occursDead cell fragments removed by phagocytes

  • *FIGURE 124 Mechanisms of apoptosis. The two pathways of apoptosis differ in their induction and regulation, and both culminate in the activation of executioner caspases. The induction of apoptosis by the mitochondrial pathway involves the action of sensors and effectors of the Bcl-2 family, which induce leakage of mitochondrial proteins. Also shown are some of the anti-apoptotic proteins (regulators) that inhibit mitochondrial leakiness and cytochrome cdependent caspase activation in the mitochondrial pathway. In the death receptor pathway engagement of death receptors leads directly to caspase activation. The regulators of death receptormediated caspase activation are not shown. ER, endoplasmic reticulum; TNF, tumor necrosis factor.

  • Apoptotic liverApoptosis is a more orderly process of cell death. Apoptosis is individual cell necrosis, not simultaneous localized necrosis of large numbers of cells. In this example, hepatocytes are dying individually (arrows) from injury through infection by viral hepatitis. The apoptotic cells are enlarged, pink from loss of cytoplasmic detail, and without nuclei. The cell nucleus and cytoplasm become fragmented as enzymes such as caspases destroy cellular components.

    *http://library.med.utah.edu/WebPath/CINJHTML/CINJ014.html

  • Apoptotic fetal thymusIn this fetal thymus there is involution of thymic lymphocytes by the mechanism of apoptosis. In this case, it is an orderly process and part of normal immune system maturation. Individual cells fragment and are consumed by phagocytes to give the appearance of clear spaces filled with cellular debris. Apoptosis is controlled by many mechanisms. Genes such as BCL-2 are turned off and Bax genes turned on. Intracellular proteolytic enzymes called caspases produce much cellular breakdown.

    *http://library.med.utah.edu/WebPath/CINJHTML/CINJ054.html

  • APOPTOSISSel mengkerutFragmentasiMembran plasma intak

    Isi sel terselubungRespon inflamasi tak ada

    NEKROSISSel membengkakDisintegrasi acakMembran plasma robekKebocoran isi selRespon inflamasi

    APOPTOSIS vs NEKROSIS

  • *FIGURE 18 Schematic illustration of the morphologic changes in cell injury culminating in necrosis or apoptosis. Cells do not recover from injury leading to apoptosis. Apoptotic cells may be isolated in tissues and not affect other cells. Necrotic cells in tissues dispense hydrolytic enzymes that damage their neighbors. Recovery from damage leading to necrosis must be early.

    *FIGURE 11 Stages of the cellular response to stress and injurious stimuli.*B, Early (reversible) ischemic injury showing surface blebs, increased eosinophilia of cytoplasm, and swelling of occasional cells.* C, Necrosis (irreversible injury) of epithelial cells, with loss of nuclei, fragmentation of cells, and leakage of contents. The ultra structural features of these stages of cell injury are shown in Figure 110. (Courtesy of Drs. Neal Pinckard and M.A. Venkatachalam, University of Texas Health Sciences Center, San Antonio, TX.)

    *FIGURE 2025 Acute kidney injury. Some of the tubular epithelial cells in the tubules are necrotic, and many have become detached (from their basement membranes) and been sloughed into the tubular lumens, whereas others are swollen, vacuolated, and regenerating. (Courtesy of Dr. Agnes Fogo, Vanderbilt University, Nashville, TN.)

    Look to see where the patterns emerge, starting with one of the two well-defined tubules. Swollen cells will have clear areas of vacuolarization due to ER smoothing, dilation, pinching. Necrotic cells are more eosinophilic (deeper pink) due to accumulation of denatured proteins and loss of RNA. Dead cells without nuclei are sloughed into tubular lumen. Dying cells have either fading, karyolytic nuclei; or condensed, pyknotic nuclei.*http://library.med.utah.edu/WebPath/CINJHTML/CINJ012.html

    Although the structure of the tissue is no longer recognizable, there are some dense, eosinophilic areas, and there are no large pools of pus or aqueous, hydrolytic areas. This is not yet, then, liquefactive necrosis.*http://library.med.utah.edu/WebPath/CINJHTML/CINJ013.html

    These cells still clearly resemble muscle.*ExpertConsult > Case Studies > Begin > Cell Injury > Introductory Images > Image 11 and 12*The small intestine is infarcted. The dark red to grey infarcted bowel contrasts with the pale pink normal bowel at the bottom. Some organs such as bowel with anastomosing blood supplies, or liver with a dual blood suppy, are hard to infarct. This bowel was caught in a hernia and the mesenteric blood supply was constricted by the small opening to the hernia sac. http://library.med.utah.edu/WebPath/CINJHTML/CINJ019.html

    GRIPE Image: 234 Item: 72-41-003-1 Organ/System: Small Intestine Diagnosis: infarct Description: coagulation necrosis transmural, submucosal edema, marked vascular congestion*http://library.med.utah.edu/WebPath/CINJHTML/CINJ015.htmlhttp://library.med.utah.edu/WebPath/CINJHTML/CINJ016.html*Gangrenous necrosis involves the tissues of a body part. The inflammation seen here is extending beneath the skin of a toe to involve soft tissue (fat and connective tissue) and bone. Because multiple tissues are non-viable, amputation of such areas is necessary. WebPath/CINJHTML/CINJ051.html

    GRIPE Images 923, 924*The liver shows a small abscess here filled with many neutrophils. This abscess is an example of localized liquefactive necrosis. This is liquefactive necrosis in the brain in a patient who suffered a "stroke" with focal loss of blood supply to a portion of cerebrum. This type of infarction is marked by loss of neurons and neuroglial cells and the formation of a clear space at the center left. As this infarct in the brain is organizing and being resolved, the liquefactive necrosis leads to resolution with cystic spaces.http://library.med.utah.edu/WebPath/CINJHTML/CINJ021.htmlhttp://library.med.utah.edu/WebPath/CINJHTML/CINJ022.html http://library.med.utah.edu/WebPath/CINJHTML/CINJ025.html *These are limited-use terms that are applied to specific damage in certain tissues, whereas nearly all tissues exhibit coagulative necrosis.*This is the gross appearance of caseous necrosis in a hilar lymph node infected with tuberculosis. The node has a cheesy tan to white appearance. Caseous necrosis is really just a combination of coagulative and liquefactive necrosis that is most characteristic of granulomatous inflammation. This is more extensive caseous necrosis, with confluent cheesy tan granulomas in the upper portion of this lung in a patient with tuberculosis. The tissue destruction is so extensive that there are areas of cavitation (cystic spaces) being formed as the necrotic (mainly liquefied) debris drains out via the bronchi. Microscopically, caseous necrosis is characterized by acellular pink areas of necrosis, as seen here at the upper right, surrounded by a granulomatous inflammatory process. http://library.med.utah.edu/WebPath/CINJHTML/CINJ028.htmlhttp://library.med.utah.edu/WebPath/CINJHTML/CINJ029.htmlhttp://library.med.utah.edu/WebPath/CINJHTML/CINJ030.html*http://library.med.utah.edu/WebPath/CINJHTML/CINJ026.htmlhttp://library.med.utah.edu/WebPath/CINJHTML/CINJ027.html*Image: 633Item: 62-40-003-2Diagnosis: acute necrotizing arteritisDescription: high power, small artery with mural edema, fibrinoid necrosishttp://peir.path.uab.edu:3555/images/med/00010628.jpgImage: 628Item: 62-40-008-2Topic: VESSELS : VasculitidesOrgan/System: MuscleDiagnosis: polyarteritisDescription: low power, angular atrophic fibers, small fibrotic artery with fibrinoid necrosis*FIGURE 117 Functional and morphologic consequences of decreased intracellular ATP during cell injury. The morphologic changes shown here are indicative of reversible cell injury. Further depletion of ATP results in cell death, typically by necrosis. ER, endoplasmic reticulum.*FIGURE 119 The role of increased cytosolic calcium in cell injury. ER, endoplasmic reticulum.*FIGURE 120 The role of reactive oxygen species (ROS) in cell injury. O2 is converted to superoxide () by oxidative enzymes in the endoplasmic reticulum (ER), mitochondria, plasma membrane, peroxisomes, and cytosol. is converted to H2O2 by dismutation and thence to OH by the Cu2+/Fe2+-catalyzed Fenton reaction. H2O2 is also derived directly from oxidases in peroxisomes (not shown). Resultant free radical damage to lipids (by peroxidation), proteins, and DNA leads to injury to numerous cellular components. The major antioxidant enzymes are superoxide dismutase (SOD), glutathione peroxidase, and catalase*FIGURE 124 Mechanisms of apoptosis. The two pathways of apoptosis differ in their induction and regulation, and both culminate in the activation of executioner caspases. The induction of apoptosis by the mitochondrial pathway involves the action of sensors and effectors of the Bcl-2 family, which induce leakage of mitochondrial proteins. Also shown are some of the anti-apoptotic proteins (regulators) that inhibit mitochondrial leakiness and cytochrome cdependent caspase activation in the mitochondrial pathway. In the death receptor pathway engagement of death receptors leads directly to caspase activation. The regulators of death receptormediated caspase activation are not shown. ER, endoplasmic reticulum; TNF, tumor necrosis factor.*http://library.med.utah.edu/WebPath/CINJHTML/CINJ014.html*http://library.med.utah.edu/WebPath/CINJHTML/CINJ054.html*FIGURE 18 Schematic illustration of the morphologic changes in cell injury culminating in necrosis or apoptosis. Cells do not recover from injury leading to apoptosis. Apoptotic cells may be isolated in tissues and not affect other cells. Necrotic cells in tissues dispense hydrolytic enzymes that damage their neighbors. Recovery from damage leading to necrosis must be early.