2507 ystem 3 googe bald ran a very similar test1 and foun
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kmr/Cell-Adap/11 1 ADAPTASI SELULER Karyono Mintaroem
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d a link to the post from inside the content (not footers/sidebars/nav). 3 weeks after these pages were re-indexed with the new link, the page dropped 2 ranking positions Bill Sebald ran a very similar test1 and found similar results (inconsistent, minor movement) My Takeaway: I’m in the process of repeating this test a few more times, but I suspect internal anchor text and links are still playing a relatively minor role (especially when it’s older pages being updated) Can Anchor Text Influence Search Suggest? A few years b
Transcript of 2507 ystem 3 googe bald ran a very similar test1 and foun
kmr/Cell-Adap/111
ADAPTASI SELULER
Karyono Mintaroem
kmr/Cell-Adap/11 2
Perubahan Morfologi
Perubahan 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.
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Perubahan fungsi / manifestasi klinik
Fungsi normal symptoms & sign, perjalanan pnykt, prognosis.
Perubahan morfologi sel / jaringan / organInteraksi sel-sel / sel-matriks
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Respon sel >< stres & stimuli yg berbahaya
(1)Program genetik
metabolisme, diferensiasi, spesialisasi
Sel tetangga Sel Normal ketersediaan fungsi & struktur substrat
metabolik homeostasis
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Sel adaptasi fisiologik homeostasis (baru) morfologik - tetap hidup - modulasi fungsi hiperplasi = Σ sel ↑ hipertrofi = Ǿ sel ↑ atrofi = Ǿ & fungsi sel ↓
metaplasia
Respon sel >< stres & stimuli yg berbahaya (3)
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Respon sel >< stres & stimuli yg berbahaya
(4)Adaptasi gagal cell injury s/d batas tertentu: reversible
Stres ↑ ↑ point of no return
cell injury irreversible
cell death
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Respon sel >< stres & stimuli yg berbahaya (2)
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Respon seluler terhadap injuryJenis & derajat stimuli
Stimuli fisiologik yg berubah: Demand ↑, Stimulasi trofik↑ Nutrien ↓, stimulasi ↓ Iritasi khronik (kimiawi, fisikal)
Suplai O2 ↓, injury kimia, infeksi mikroba : Akut & self limited Progresif & Berat (rusaknya DNA)
Injury ringan khronik
Perubahan metabolik, genetik / didapatWaktu hidup lama dg akumulasi injury
sublethal
Respon selulerAdaptasi seluler
Hiperplasia, hipertrofiAtrofiMetaplasia
Cell injury :Injury reversible akutIrrebersible injury cell death
Nekrosis Apoptosis
Perubahan subseluler bbrp organela
Akumulasi intraseluler,kalsifikasiCelluler aging
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Adaptasi seluler pada pertumbuhan & diferensiasi
Bentuk adaptasi :hiperplasiahipertrofiatrofimetaplasia
Mekanisme molekulernya bermacam-macam
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HIPERPLASIA (1)Σ sel pd organ/jaringan ↑ volume organ/jaringan ↑Hiperplasia fisiologik :
Hiperplasia hormonal
Hiperplasia kompensatoir
Mekanisme hiperplasia : Produksi Growth Factor ↑ produksi Level GF Receptor ↑ faktor Aktivasi lintasan signal intraseluler transkripsi ↑
Aktivasi gen-gen seluler proliferasi sel
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HIPERPLASIA (2)
Hiperplasia patologik :Hiperplasia ok induksi hormonal >> :
Hiperplasia endometriumHiperplasia ok induksi GF >> :
Pada penyembuhan lukajar. parut (proliferasi fibroblast)
Infeksi virus : papilloma virus wart (hiperplasia epitelium)
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HIPERTROFI (1)Ukuran sel ↑ ukuran organ ↑
Tidak ada sel baru !!! Sintesa komponen struktural sel ↑DNA inti sel hipertrofi >> inti sel biasa
Mekanisme 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.
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HIPERTROFI (2)Gen yg terlibat :
Yg mengkode faktor transkripsi : c-fos, c-jun
GF : TGF-β, IGF-1, Fibroblast GFAgen Vasoaktif : α-adrenergic agonist,
endothelin-1, angiotensin II
Hiperplasia & hipertrofi sering terjadi bersamaan
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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,
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ATROFI (2)Atrofi pathologik :
Lokal / general (sistemik) jenis causa.Beban ↓(atrophy of disuse) :
pd immobilisasi, mis : frakturInnervasi (-) = denervation atrophySuplai darah ↓(ischemia) : atrofi otak pd lansia.Nutrisi tak cukup : marasmus penyakit keradangan khronis cachexia kanker
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ATROFI (3)Penekanan (pressure) :
penekanan, wkt lama atrofiǾ 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
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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
rokokepitel kolumnar sektretorikepitel skuamous
bertatah : duktus kel. Liur, pankreas, d. choledochus ; ok batu
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METAPLASIA (2)Epitel skuamousepitel kolumnar intestinal :
esofagus distal, : Barrett metaplasia.Metaplasia jar. ikatcartilago, tulang, jar. lemak.Contoh : pembentukan jar tulang didalam otot =
myositis ossificans, fraktura
Mekanisme metaplasia :Pemrograman ulang stem cells yg sdh ada.signalstimuli sitokin, GF, komponen matriks ekstraselulerdiferensiasi stem cell.Melibatkan gen-2 pengatur diferensiasi.
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Cell injury & Cell deathSel sakit & sel mati (1)
Mekanisme :
Reversible cell injury :stimuli yg merusak perub. morfo. & fungsitanda-2 : fosforilasi oksidatif ↓
adenosin trifosfat (ATP) ↓ pembengkakan sel : ok
perub konsentrasi ionair masuk kedlm sel (water
influx)
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Cell injury & Cell deathSel 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
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Nekrosis
Ukuran selIntiMembran plasmaIsi sel
Reaksi radang sekitarFungsi fisio /
patologik
Membesar / swellingPyknosis karyolysisPecah / disruptedPencernakan
enzimatik,Sel bocorSeringPatologik,
bervariasi :fase akhir dr injury sel yg irreversible
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ApoptosisMengecil /shrinkageFragmentasiUtuh/intact, perubahan
struktur : lemak
Utuh; lepas sbgai apoptotic bodies
Tidak adaSering fisiologik :
eliminasi sel yg tidak perlu
Patologik : kerusakan DNA
Ukuran selIntiMembran plasma
Isi sel
Reaksi radang sekitarFungsi fisio / patologik
Features of Necrosis and Apoptosis
Feature Necrosis ApoptosisCell size Enlarged (swelling) Reduced (shrinkage)
Nucleus Pyknosis → karyorrhexis → karyolysis
Fragmentation into nucleosome-size fragments
Plasma membrane
Disrupted Intact; altered structure, especially orientation of lipids
Cellular contents
Enzymatic digestion; may leak out of cell
Intact; may be released in apoptotic bodies
Adjacent inflammation
Frequent No
Physiologic or pathologic role
Invariably pathologic (culmination of irreversible cell injury
Often physiologic, means of eliminating unwanted cells; may be pathologic after some forms of cell injury, especially DNA damage
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Causa Cell injury (1)1. Kekurangan oksigen (hypoxia)
Kegagalan kardiorespirasiPe ↓ kapasitas pengangkutan oksigen
anemia, keracunan CO
2. Bahan fisik :Trauma mekanisSuhu ekstrim (panas / dingin)
3. Bahan kimia / obat :Larutan hipertonikOksigen konsentrasi tinggi
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Causa Cell injury (2)Racun : arsen, sianid, garam merkuriLain-2 : polutan, insektisid, herbisid, Produk industri : CO, asbesAlkohol & narkoba.
4. Bahan infeksious :Virus – bakteri – jamur – parasit (cacing pita)
5. Reaksi imunologik :Reaksi anafilaksisReaksi autoimun
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Causa Cell injury (3)6. Kelainan genetik :
Down syndromeSickle cell anemia
7. Ketidak seimbangan nutrisi :Defisiensi protein-kaloriDefisiensi vitaminLipid berlebihan : obesitas, atherosclerosisPenyakit metabolik : diabetes
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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.
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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.
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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
apoptosis
4. Akumukasi radikal bebas derivat oksigen
(oxidative stress).contoh : O2
-*, H2O2, OH*.
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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↓.
Berkurangnya ATP
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Disfungsi Mitochondria
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Peningkatan Ca sitosolik
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Morfologi Sel Sakit & NekrosisSel sakit reversible : (mikroskopik )
Celluler swelling = pembengkakan / edema / hidropik / degen. vacuolarFatty change = perlemakan
Fungsi membran plasma trgg → homeostasis cairan & inti trgg → edema sel
Injury : hipoxia/toksik/metabolik → vacuola lipid didalam sitoplasma (fatty change)
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Morfologi Sel Sakit reversible :Makroskopik : pd organ
lebih pucat, turgor ↑, berat ↑.
Mikroskopik :vakuola kecil, jernih (sulit dilihat).
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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.
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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 enzimMerupakan tanda infeksi bakteri, kadang jamur.Apapun patogenesisnya, liquefaksi mencernak habis seluruh sel mati → massa liquid viskous.Rad. Akut → lekosit mati↑ ↑ → massa :krim kekuningan=
pus
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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.
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Nekrosis (4)Mikroskopik ;
bayangan sel lemak nekrotik, kalsium deposit basofilik, dikelilingi keradangan.
Makroskopik ;daerah putih, seperti kapur (kalsium + asam lemak) = fat saponification.
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Figure 1-10 Cellular and biochemical sites of damage in cell injury.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:00 AM)© 2005 Elsevier
kmr/Cell-Adap/11 48Figure 1-11 Functional and morphologic consequences of decreased intracellular ATP during cell injury.
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Figure 1-12 Mitochondrial dysfunction in cell injury.
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kmr/Cell-Adap/11 50Figure 1-13 Sources and consequences of increased cytosolic calcium in cell injury. ATP, adenosine triphosphate.
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Figure 1-16 Timing of biochemical and morphologic changes in cell injury.
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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.
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Figure 1-15 Mechanisms of membrane damage in cell injury. Decreased O2 and increased cytosolic Ca2+ are typically seen in ischemia 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).Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 February 2005 02:01 AM)
© 2005 Elsevier
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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 membrane
damage. ER, endoplasmic reticulum; CK, creatine kinase; LDH, lactate dehydrogenase; RNP, ribonucleoprotein.
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Figure 1-18 Ischemic necrosis of the myocardium. A, Normal myocardium. B, Myocardium with coagulation necrosis (upper two thirds of figure), showing strongly eosinophilic anucleate myocardial fibers. Leukocytes in the
interstitium are an early reaction to necrotic muscle. Compare with A and with normal fibers in the lower part of the figure.
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Figure 1-19 Coagulative and liquefactive necrosis. A, Kidney infarct exhibiting coagulative necrosis, with loss of nuclei 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.
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Figure 1-20 A tuberculous lung with a large area of caseous necrosis. The caseous debris is yellow-white and cheesy.
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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.
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Terima kasih
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