1. Cellular adaptation and injury can occur through morphological, functional, and biochemical changes in cells in response to stressors or stimuli. 2. Adaptive responses include hyperplasia, hypertrophy, atrophy, and metaplasia through molecular mechanisms. Failure to adapt can lead to reversible or irreversible cell injury and cell death through necrosis or apoptosis. 3. Causes of cell injury include hypoxia, physical and chemical factors, infectious agents, immune reactions, genetic defects, and nutritional imbalances. Injury disrupts ATP production, damages mitochondria, increases intracellular calcium, and causes oxidative stress and membrane permeability defects.

1. ADAPTASI SELULER
Karyono Mintaroem
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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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3. Perubahan fungsi / manifestasi
klinik
Fungsi normal symptoms & sign,
perjalanan pnykt,
prognosis.
Perubahan morfologi sel / jaringan / organ
Interaksi sel-sel / sel-matriks
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4. 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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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
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6. 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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7. Respon sel ><
stres & stimuli yg berbahaya (2)
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9. Respon seluler terhadap injury
Jenis & derajat stimuli Respon seluler
Stimuli fisiologik yg berubah: Adaptasi seluler
Demand ↑, Stimulasi trofik↑ Hiperplasia, hipertrofi
Nutrien ↓, stimulasi ↓ Atrofi
Iritasi khronik (kimiawi, fisikal) Metaplasia
Suplai 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
organela
Perubahan metabolik, genetik / didapat Akumulasi intraseluler,kalsifikasi
Waktu hidup lama dg akumulasi injury Celluler aging
sublethal
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10. Adaptasi seluler pada
pertumbuhan & diferensiasi
Bentuk adaptasi :
hiperplasia
hipertrofi
atrofi
metaplasia
Mekanisme molekulernya bermacam-macam
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11. 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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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)
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13. 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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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 II
Hiperplasia & hipertrofi sering terjadi bersamaan
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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,
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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
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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
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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
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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,  fraktura
Mekanisme metaplasia :
Pemrograman ulang stem cells yg sdh ada.
signalstimuli sitokin, GF, komponen matriks
ekstraselulerdiferensiasi stem cell.
Melibatkan gen-2 pengatur diferensiasi.
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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)
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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
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28. Nekrosis
Ukuran sel Membesar / swelling
Inti Pyknosis  karyolysis
Membran plasma Pecah / disrupted
Isi sel Pencernakan enzimatik,
Sel bocor
Reaksi radang sekitar Sering
Fungsi fisio / patologik Patologik, bervariasi :
fase akhir dr injury sel
yg irreversible
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29. Apoptosis
Ukuran sel Mengecil /shrinkage
Inti Fragmentasi
Membran plasma Utuh/intact, perubahan
struktur : lemak
Isi sel Utuh; lepas sbgai apoptotic
bodies
Reaksi radang sekitar Tidak ada
Fungsi fisio / patologik Sering fisiologik : eliminasi
sel yg tidak perlu
Patologik : kerusakan
DNA
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30. Features of Necrosis and Apoptosis
Feature Necrosis Apoptosis
Cell size Enlarged (swelling) Reduced (shrinkage)
Nucleus Pyknosis → karyorrhexis Fragmentation into nucleosome-
→ karyolysis size fragments
Plasma Disrupted Intact; altered structure,
membrane especially orientation of lipids
Cellular Enzymatic digestion; may Intact; may be released in
contents leak out of cell apoptotic bodies
Adjacent Frequent No
inflammation
Physiologic Invariably pathologic Often physiologic, means of
or pathologic (culmination of eliminating unwanted cells; may
role irreversible cell injury be pathologic after some forms of
cell injury, especially DNA damage

31. Causa Cell injury (1)
1. Kekurangan oksigen (hypoxia)
Kegagalan kardiorespirasi
Pe ↓ kapasitas pengangkutan oksigen
anemia, keracunan CO
2. Bahan fisik :
Trauma mekanis
Suhu ekstrim (panas / dingin)
3. Bahan kimia / obat :
Larutan hipertonik
Oksigen konsentrasi tinggi
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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
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33. Causa Cell injury (3)
6. Kelainan genetik :
Down syndrome
Sickle cell anemia
7. Ketidak seimbangan nutrisi :
Defisiensi protein-kalori
Defisiensi vitamin
Lipid berlebihan : obesitas, atherosclerosis
Penyakit metabolik : diabetes
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34. Mekanisme Cell injury
Mekanisme 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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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.
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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
apoptosis
4. Akumukasi radikal bebas derivat oksigen
(oxidative stress).
contoh : O2-*, H2O2, OH*.
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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↓.
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38. Berkurangnya ATP
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39. Disfungsi Mitochondria
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40. Peningkatan Ca sitosolik
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41. Morfologi Sel Sakit & Nekrosis
Sel sakit reversible : (mikroskopik )
Celluler swelling = pembengkakan / edema /
hidropik / degen. vacuolar
Fatty 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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42. Morfologi Sel Sakit reversible :
Makroskopik : pd organ
lebih pucat, turgor ↑, berat ↑.
Mikroskopik :
vakuola kecil, jernih (sulit dilihat).
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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.
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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
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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.
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46. 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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47. Figure 1-10 Cellular and biochemical sites of damage in cell injury.
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48. Figure 1-11 Functional and morphologic consequences of decreased intracellular ATP during cell injury.
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49. Figure 1-12 Mitochondrial dysfunction in cell injury.
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50. Figure 1-13 Sources and consequences of increased cytosolic calcium in cell injury. ATP, adenosine triphosphate.
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51. Figure 1-16 Timing of biochemical and morphologic changes in cell injury.
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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.
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53. 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).
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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 membrane
damage. ER, endoplasmic reticulum; CK, creatine kinase; LDH, lactate dehydrogenase; RNP, ribonucleoprotein.
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55. 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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56. 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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57. 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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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.
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59. Terima kasih
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