Adaptasi seluler

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Adaptasi seluler

  1. 1. ADAPTASI SELULERKaryono Mintaroem kmr/Cell-Adap/11 1
  2. 2. Perubahan MorfologiPerubahan morfologi = perubahan struktur sel / jaringan / organ  ciri-ciri penyakit / dx proses etiologik.Perub. Morfo. + biomol + imunologik  ciri- ciri pnykt / perjalanan pnykt / pndktn tx / prognosis  lbh jelas. kmr/Cell-Adap/11 2
  3. 3. Perubahan fungsi / manifestasi klinikFungsi normal symptoms & sign, perjalanan pnykt, prognosis. Perubahan morfologi sel / jaringan / organ Interaksi sel-sel / sel-matriks kmr/Cell-Adap/11 3
  4. 4. Respon sel >< stres & stimuli yg berbahaya (1) Program genetik metabolisme, diferensiasi, spesialisasiSel tetangga Sel Normal ketersediaan fungsi & struktur substrat metabolik homeostasis kmr/Cell-Adap/11 4
  5. 5. Respon sel >< stres & stimuli yg berbahaya (3)Sel adaptasi  fisiologik  homeostasis (baru) morfologik - tetap hidup - modulasi fungsi hiperplasi = Σ sel ↑ hipertrofi = Ǿ sel ↑ atrofi = Ǿ & fungsi sel ↓ metaplasia kmr/Cell-Adap/11 5
  6. 6. Respon sel >< stres & stimuli yg berbahaya (4)Adaptasi gagal cell injury s/d batas tertentu: reversibleStres ↑ ↑ point of no return cell injury irreversible cell death kmr/Cell-Adap/11 6
  7. 7. Respon sel ><stres & stimuli yg berbahaya (2) kmr/Cell-Adap/11 7
  8. 8. kmr/Cell-Adap/11 8 Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 11 February 2005 04:43 PM) © 2005 Elsevier
  9. 9. Respon seluler terhadap injury Jenis & derajat stimuli Respon selulerStimuli fisiologik yg berubah: Adaptasi seluler Demand ↑, Stimulasi trofik↑ Hiperplasia, hipertrofi Nutrien ↓, stimulasi ↓ Atrofi Iritasi khronik (kimiawi, fisikal) MetaplasiaSuplai O2 ↓, injury kimia, infeksi mikroba : Cell injury : Akut & self limited Injury reversible akut Progresif & Berat (rusaknya DNA) Irrebersible injury  cell death Nekrosis Apoptosis Injury ringan khronik Perubahan subseluler bbrp organelaPerubahan metabolik, genetik / didapat Akumulasi intraseluler,kalsifikasiWaktu hidup lama dg akumulasi injury Celluler aging sublethal kmr/Cell-Adap/11 9
  10. 10. Adaptasi seluler pada pertumbuhan & diferensiasiBentuk adaptasi : hiperplasia hipertrofi atrofi metaplasiaMekanisme molekulernya bermacam-macam kmr/Cell-Adap/11 10
  11. 11. HIPERPLASIA (1)Σ sel pd organ/jaringan ↑  volume organ/jaringan ↑Hiperplasia fisiologik : Hiperplasia hormonal Hiperplasia kompensatoirMekanisme hiperplasia : Produksi Growth Factor ↑ produksi Level GF Receptor ↑ faktor Aktivasi lintasan signal intraseluler transkripsi ↑  Aktivasi gen-gen seluler  proliferasi sel kmr/Cell-Adap/11 11
  12. 12. HIPERPLASIA (2)Hiperplasia patologik : Hiperplasia ok induksi hormonal >> : Hiperplasia endometrium Hiperplasia ok induksi GF >> : Pada penyembuhan lukajar. parut (proliferasi fibroblast) Infeksi virus : papilloma virus  wart (hiperplasia epitelium) kmr/Cell-Adap/11 12
  13. 13. HIPERTROFI (1)Ukuran sel ↑  ukuran organ ↑ Tidak ada sel baru !!! Sintesa komponen struktural sel ↑ DNA inti sel hipertrofi >> inti sel biasaMekanisme hipertrofi : a. Induksi hormonal : gland. Mamma, uterus. b. Mekanik : beban ↑, stretch : otot jantung, ORwan.a+b  lintasan signal transduksi  induksi gen-2  stimulasi sintesa protein sel. kmr/Cell-Adap/11 13
  14. 14. HIPERTROFI (2)Gen yg terlibat : Yg mengkode faktor transkripsi : c-fos, c-jun GF : TGF-β, IGF-1, Fibroblast GF Agen Vasoaktif : α-adrenergic agonist, endothelin-1, angiotensin IIHiperplasia & hipertrofi sering terjadi bersamaan kmr/Cell-Adap/11 14
  15. 15. kmr/Cell-Adap/11 15
  16. 16. ATROFI (1) “Pengkerutan / pengecilan sel akibat hilangnya substansi sel”Merupakan respon adaptasi yg bisa berakhir dengan kematian sel (cell death).Atrofi fisiologik : pdu selama perkembangan awal, misal : Kel. Thymus, ductus thyroglossus, pd dewasa / lanjut (senile atrophy), misal : Uterus setelah persalinan, glan. mamma, epitel vagina, otak, jantung, kmr/Cell-Adap/11 16
  17. 17. ATROFI (2)Atrofi pathologik : Lokal / general (sistemik) jenis causa. Beban ↓(atrophy of disuse) : pd immobilisasi, mis : fraktur Innervasi (-) = denervation atrophy Suplai darah ↓(ischemia) : atrofi otak pd lansia. Nutrisi tak cukup : marasmus penyakit keradangan khronis  cachexia kanker kmr/Cell-Adap/11 17
  18. 18. ATROFI (3)Penekanan (pressure) : penekanan, wkt lama  atrofi Ǿ tu ↑ ↑  ischemik jar sekitar  atrofi.Pd sel otot yg atrofi : mitochondria/myofilamen/e.r.: ↓ ↓.Mekanisme atrofi : belum seluruhnya jelas. “ degradsi protein oleh enzim-enzim / sitokin” a.l.: lysosom, proteasom, TNF kmr/Cell-Adap/11 18
  19. 19. kmr/Cell-Adap/11 19
  20. 20. METAPLASIA (1)“Pergantian satu jenis sel dewasa ke jenis sel dewasa yg lain & reversible”Sel epitel maupun sel mesenchymal.Contoh : epitel kolumnar bersilia epitel skuamous bertatah : bronkhus, ok asap rokok epitel kolumnar sektretorikepitel skuamous bertatah : duktus kel. Liur, pankreas, d. choledochus ; ok batu kmr/Cell-Adap/11 20
  21. 21. METAPLASIA (2)Epitel skuamousepitel kolumnar intestinal : esofagus distal, : Barrett metaplasia.Metaplasia jar. ikatcartilago, tulang, jar. lemak.Contoh : pembentukan jar tulang didalam otot = myositis ossificans,  frakturaMekanisme metaplasia : Pemrograman ulang stem cells yg sdh ada. signalstimuli sitokin, GF, komponen matriks ekstraselulerdiferensiasi stem cell. Melibatkan gen-2 pengatur diferensiasi. kmr/Cell-Adap/11 21
  22. 22. kmr/Cell-Adap/11 22
  23. 23. Cell injury & Cell death Sel sakit & sel mati (1)Mekanisme :Reversible cell injury : stimuli yg merusak perub. morfo. & fungsi tanda-2 : fosforilasi oksidatif ↓ adenosin trifosfat (ATP) ↓ pembengkakan sel : ok perub konsentrasi ion air masuk kedlm sel (water influx) kmr/Cell-Adap/11 23
  24. 24. Cell injury & Cell death Sel sakit & sel mati (2)Irreversible injury & cell death :Stimuli ↑ ↑  kerusakan ↑ ↑ sel mati (irreversible)Contoh : pd myocardium dg ischemia : perub struktur pd mitochondria :  bhn amorf yg padat perub fungsi mitochondria :  permeabilitas membran (-) tanda sel mengalami injury irreversible kmr/Cell-Adap/11 24
  25. 25. kmr/Cell-Adap/11 Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 11 February 2005 04:43 PM) 25 © 2005 Elsevier
  26. 26. kmr/Cell-Adap/11 Robbins & Cotran Pathologic Basis of Disease (on 11 February 2005 04:43 PM) 26 Downloaded from: © 2005 Elsevier
  27. 27. kmr/Cell-Adap/11 Robbins & Cotran Pathologic Basis of Disease (on 11 February 2005 04:43 PM) 27 Downloaded from: © 2005 Elsevier
  28. 28. NekrosisUkuran sel Membesar / swellingInti Pyknosis  karyolysisMembran plasma Pecah / disruptedIsi sel Pencernakan enzimatik, Sel bocorReaksi radang sekitar SeringFungsi fisio / patologik Patologik, bervariasi : fase akhir dr injury sel yg irreversible kmr/Cell-Adap/11 28
  29. 29. ApoptosisUkuran sel Mengecil /shrinkageInti FragmentasiMembran plasma Utuh/intact, perubahan struktur : lemakIsi sel Utuh; lepas sbgai apoptotic bodiesReaksi radang sekitar Tidak adaFungsi fisio / patologik Sering fisiologik : eliminasi sel yg tidak perlu Patologik : kerusakan DNA kmr/Cell-Adap/11 29
  30. 30. Features of Necrosis and ApoptosisFeature Necrosis ApoptosisCell size Enlarged (swelling) Reduced (shrinkage)Nucleus Pyknosis → karyorrhexis Fragmentation into nucleosome- → karyolysis size fragmentsPlasma Disrupted Intact; altered structure,membrane especially orientation of lipidsCellular Enzymatic digestion; may Intact; may be released incontents leak out of cell apoptotic bodiesAdjacent Frequent NoinflammationPhysiologic Invariably pathologic Often physiologic, means ofor pathologic (culmination of eliminating unwanted cells; mayrole irreversible cell injury be pathologic after some forms of cell injury, especially DNA damage
  31. 31. Causa Cell injury (1)1. Kekurangan oksigen (hypoxia) Kegagalan kardiorespirasi Pe ↓ kapasitas pengangkutan oksigen anemia, keracunan CO2. Bahan fisik : Trauma mekanis Suhu ekstrim (panas / dingin)3. Bahan kimia / obat : Larutan hipertonik Oksigen konsentrasi tinggi kmr/Cell-Adap/11 31
  32. 32. Causa Cell injury (2) Racun : arsen, sianid, garam merkuri Lain-2 : polutan, insektisid, herbisid, Produk industri : CO, asbes Alkohol & narkoba.4. Bahan infeksious : Virus – bakteri – jamur – parasit (cacing pita)5. Reaksi imunologik : Reaksi anafilaksis Reaksi autoimun kmr/Cell-Adap/11 32
  33. 33. Causa Cell injury (3)6. Kelainan genetik : Down syndrome Sickle cell anemia7. Ketidak seimbangan nutrisi : Defisiensi protein-kalori Defisiensi vitamin Lipid berlebihan : obesitas, atherosclerosis Penyakit metabolik : diabetes kmr/Cell-Adap/11 33
  34. 34. Mekanisme Cell injuryMekanisme biokimiawi sel sakit: sangat kompleks.3 prinsip :1. Respon seluler tergantung pd : jenis injury, lamanya, berat-ringannya.2. Manifestasi tergantung pd : tipe, status dan kemampuan adaptasi sel yg mengalami injury.3. Sel sakit merupakan akibat dr abnormalitas fungsi dan proses biokimiawi bbrp komponen penting dalam sel. kmr/Cell-Adap/11 34
  35. 35. Mekanisme biokimia yg terjadi:(1)1. Hilangnya ATP / menurunnya sintesa ATP. pdu ok injury hipoksia / kimiawi toksik. ATP perlu utk proses-2 sintesa / degradasi ; sintesa protrin, membrane transport, lipogenesis, metab. fosfolipid., dll.2. Kerusakan mitochondria. ok : Ca++ sitosol ↑, stres oksidatif, terurainya fosfolipid, lepasnya cytochrome c ke sitosol. kmr/Cell-Adap/11 35
  36. 36. Mekanisme biokimia yg terjadi (2)3. Influx Ca intraseluler & gangguan homeostasis Ca ok : ischemia, toksin. Ca ↑, → Aktivasi enzim-2 al : ATPase, fosfolipase, protease, endonuclease. Permeabilitas mitochondria ↑, → induksi apoptosis4. Akumukasi radikal bebas derivat oksigen (oxidative stress). contoh : O2-*, H2O2, OH*. kmr/Cell-Adap/11 36
  37. 37. Mekanisme biokimia yg terjadi (3)5. Defek permeabilitas membran. Yg terkena : membran plasma, membran mitochondria, dll. Causa : Membran plasma : toksin bakteri, protein virus, bhn fisikal / kimiawi. Mitochondria : hipoxia, ATP↓. kmr/Cell-Adap/11 37
  38. 38. Berkurangnya ATP kmr/Cell-Adap/11 38
  39. 39. Disfungsi Mitochondria kmr/Cell-Adap/11 39
  40. 40. Peningkatan Ca sitosolik kmr/Cell-Adap/11 40
  41. 41. Morfologi Sel Sakit & NekrosisSel sakit reversible : (mikroskopik ) Celluler swelling = pembengkakan / edema / hidropik / degen. vacuolar Fatty change = perlemakanFungsi membran plasma trgg → homeostasis cairan& inti trgg → edema selInjury : hipoxia/toksik/metabolik → vacuola lipid didalam sitoplasma (fatty change) kmr/Cell-Adap/11 41
  42. 42. Morfologi Sel Sakit reversible :Makroskopik : pd organ lebih pucat, turgor ↑, berat ↑.Mikroskopik : vakuola kecil, jernih (sulit dilihat). kmr/Cell-Adap/11 42
  43. 43. Nekrosis (1)Akibat dari : denaturasi protein intraseluler pencernakan enzimatik .Sel tampak lbh eosinofilik, homogen spt kaca (glassy homogenous), vacuole dlm sitoplasma, kalsifikasi.Perubahan-2 pd inti : karyolysis : chromatin memudar (basofilik / kebiruan ↓) pyknosis : inti mengkerut, lbh basofilik. karyorrhexis : inti pyknotik → fragmentasi. kmr/Cell-Adap/11 43
  44. 44. Nekrosis (2)Nekrosis koagulatif : terutama ok denaturasi Sel tampak acidofilik, tidak berinti, arsitektur Jaringan masih nampak (terutam bila ok hipoksia) contoh : infark jantung, infark ginjal.Nekrosis liquefaktif : terutama ok digestif enzim Merupakan tanda infeksi bakteri, kadang jamur. Apapun patogenesisnya, liquefaksi mencernak habis seluruh sel mati → massa liquid viskous. Rad. Akut → lekosit mati↑ ↑ → massa :krim kekuningan= pus kmr/Cell-Adap/11 44
  45. 45. Nekrosis (3)Nekrosis kaseosa :bentuk khusus nekrosis koagulatif. Sering pd TBC. Caseous  “cheesey white”. Mikros : debris granuler, amorf (trdr fragmen sel-2 yg koagulatif), dikelilingi keradangan.  “reaksi / keradangan granulomatous. Arsitektur jaringan hilang.Nekrosis lemak (Fat necrosis) : Bukan pola/jenis nekrosis yg sebenarnya. contoh : pancreatitis akut  lipase keluar  liquifaksi sel lemak. kmr/Cell-Adap/11 45
  46. 46. Nekrosis (4)Mikroskopik ; bayangan sel lemak nekrotik, kalsium deposit basofilik, dikelilingi keradangan.Makroskopik ; daerah putih, seperti kapur (kalsium + asam lemak) = fat saponification. kmr/Cell-Adap/11 46
  47. 47. Figure 1-10 Cellular and biochemical sites of damage in cell injury. kmr/Cell-Adap/11 Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:00 AM) 47 Downloaded from: © 2005 Elsevier
  48. 48. Figure 1-11 Functional and morphologic consequences of decreased intracellular ATP during cell injury. kmr/Cell-Adap/11 Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:00 AM) 48 Downloaded from: © 2005 Elsevier
  49. 49. Figure 1-12 Mitochondrial dysfunction in cell injury. kmr/Cell-Adap/11 Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:00 AM) 49 Downloaded from: © 2005 Elsevier
  50. 50. Figure 1-13 Sources and consequences of increased cytosolic calcium in cell injury. ATP, adenosine triphosphate. kmr/Cell-Adap/11 Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:00 AM) 50 Downloaded from: © 2005 Elsevier
  51. 51. Figure 1-16 Timing of biochemical and morphologic changes in cell injury. kmr/Cell-Adap/11 Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:00 AM) 51 Downloaded from: © 2005 Elsevier
  52. 52. Figure 1-14 The role of reactive oxygen species in cell injury. O2 is converted to superoxide (O2-) by oxidative enzymes in the endoplasmic reticulum (ER), mitochondria, plasma membrane, peroxisomes, and cytosol. O2- 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 is another potentially injurious radical, singlet oxygen. Resultant free radical damage to lipid (peroxidation), proteins, and DNA leads to various forms of cell injury. Note that superoxide catalyzes the reduction of Fe3+ to Fe2+,thus enhancing OH generation by the Fenton reaction. The major antioxidant enzymes are superoxide dismutase (SOD), catalase, and glutathione peroxidase. GSH, reduced glutathione; GSSG, oxidized glutathione; NADPH, reduced form of nicotinamide adenine dinucleotide phosphate. kmr/Cell-Adap/11 Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:01 AM) 52 Downloaded from: © 2005 Elsevier
  53. 53. Figure 1-15 Mechanisms of membrane damage in cell injury. Decreased O2 and increased cytosolic Ca2+ are typically seen inischemia but may accompany other forms of cell injury. Reactive oxygen species, which are often produced on reperfusion of ischemic tissues, also cause membrane damage (not shown). kmr/Cell-Adap/11 Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:01 AM) 53 Downloaded from: © 2005 Elsevier
  54. 54. Figure 1-22 Postulated sequence of events in reversible and irreversible ischemic cell injury. Note that although reduced oxidative phosphorylation and ATP levels have a central role, ischemia can cause direct membranedamage. ER, endoplasmic reticulum; CK, creatine kinase; LDH, lactate dehydrogenase; RNP, ribonucleoprotein. kmr/Cell-Adap/11 Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:01 AM) 54 © 2005 Elsevier
  55. 55. Figure 1-18 Ischemic necrosis of the myocardium. A, Normal myocardium. B, Myocardium with coagulationnecrosis (upper two thirds of figure), showing strongly eosinophilic anucleate myocardial fibers. Leukocytes in theinterstitium are an early reaction to necrotic muscle. Compare with A and with normal fibers in the lower part of the figure. kmr/Cell-Adap/11 Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:01 AM) 55 © 2005 Elsevier
  56. 56. Figure 1-19 Coagulative and liquefactive necrosis. A, Kidney infarct exhibiting coagulative necrosis, with loss ofnuclei and clumping of cytoplasm but with preservation of basic outlines of glomerular and tubular architecture. B, A focus of liquefactive necrosis in the kidney caused by fungal infection. The focus is filled with white cells and cellular debris, creating a renal abscess that obliterates the normal architecture. kmr/Cell-Adap/11 Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:01 AM) 56 © 2005 Elsevier
  57. 57. Figure 1-20 A tuberculous lung with a large area of caseous necrosis. The caseous debris is yellow-white and cheesy. kmr/Cell-Adap/11 Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:01 AM) 57 © 2005 Elsevier
  58. 58. Figure 1-21 Foci of fat necrosis with saponification in the mesentery. The areas of white chalky deposits represent calcium soap formation at sites of lipid breakdown. kmr/Cell-Adap/11 Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:01 AM) 58 © 2005 Elsevier
  59. 59. Terima kasih kmr/Cell-Adap/11 59

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