Jejas dan

Adaptasi Sel
Bagian Biomedika Kedokteran Gigi
Fakultas Kedokteran Gigi
Universitas Gadjah Mada

Jejas dan Adaptasi

Sel normal berada dalam kondisi
homeostasis.
Apakah yang dimaksud kondisi
homeostasis itu? (Parameter
fisiologis)
Homoios (same, like, resembling)
and stasis (to stand, posture).

Homeostasis
Homoios (same, like,
resembling) dan
stasis (to stand,
posture)
Claude Bernard
(1813-1878), Bapak
Fisiologi

Jejas dan Adaptasi

Pada kondisi adanya stres fisiologis ataupun
stimulus patologis, sel beradaptasi.
(1) mencapai steady state yang baru, (2) untuk
mempertahankan viabilitas, (3) dan
mempertahankan fungsi.
Adaptasi: hipertrofi, hiperplasia, atrofi, dan
metaplasia.

Jejas dan Adaptasi

Apabila stimulus melampaui kemampuan sel
beradaptasi, maka terjadilah jejas (injury).
Reversibel, dan ireversibel.

Adaptasi Sel
Adaptasi Fisiologis: respon sel
terhadap rangsangan hormonal
maupun faktor kimiawi endogenus
(misal pembesaran dada dan uterus
saat kehamilan).
Adaptasi Patologis: Sel memodulasi
struktur dan fungsi agar tidak terjadi
jejas.

Hipertrofi
Perubahan ukuran sel (menjadi besar) dan
menyebabkan pembesaran organ.
Triger mekanis (mechanical trigger): misal
peregangan otot jantung
Triger trofik (trophic trigger): aktivasi aadrenergik.

Physiologic hypertrophy of the uterus during pregnancy.

A, Gross appearance of a normal uterus (right
( right)) and a gravid uterus (left
(left)) that was
removed for postpartum bleeding. B, Small spindlespindle-shaped uterine smooth
muscle cells from a normal uterus. Compare this with (C) large, plump
hypertrophied smooth muscle cells from a gravid uterus (B and C, same
magnification).

Hiperplasia
Pertambahan jumlah sel karena sebab
fisiologis maupun patologis.
Fisiologis: hormonal hiperplasia,
kompensatori hiperplasia (compensatory
hyperplasia).
Patologis: Lesi mukosa menyebabkan
epitel mengalami hiperplasia.

Atrofi
Pengerutan ukuran sel karena hilangnya
substansi sel.
Misalnya: nutrisi yang tidak mencukupi,
hilangnya stimulasi endokrin, kurangnya
supply darah, atau penuaan (senile
hypertrophy).

Atrophy. A, Normal brain of a young adult. B, Atrophy of the brain in an 82-year-old male with atherosclerotic disease.
Atrophy of the brain is due to aging and reduced blood supply. Note that loss of brain substance narrows the gyri and
widens the sulci. The meninges have been stripped from the right half of each specimen to reveal the surface of the brain.

Metaplasia
Perubahan reversibel yang terjadi saat
jenis sel tertentu digantikan oleh jenis sel
yang lain (epitelial atau mesenkhimal).
Disebabkan karena genetic
reprogramming.

Hypertrophy: increased cell and organ size, often in response to

increased workload; induced by mechanical stress and by
growth factors; occurs in tissues incapable of cell division
Hyperplasia: increased cell numbers in response to hormones
and other growth factors; occurs in tissues whose cells are able
to divide
Atrophy: decreased cell and organ size, as a result of decreased
nutrient supply or disuse; associated with decreased synthesis
and increased proteolytic breakdown of cellular organelles
Metaplasia: change in phenotype of differentiated cells, often a
response to chronic irritation that makes cells better able to
withstand the stress; usually induced by altered differentiation
pathway of tissue stem cells; may result in reduced functions or
increased propensity for malignant transformation.

Jejas Reversibel dan

Ireversibel
Reversibel
Kematian Sel: Nekrosis dan Apoptosis,
berbeda secara morfologis, mekanisme,
peran dalam perkembangan penyakit dan
fisiologis.

Penyebab Jejas Sel

Oxygen depriviation
depriviation::
Hypoxia atau defisiensi oksigen (berbeda dengan
ischemia).
ischemia
). Iskemia adalah berkurangnya aliran darah
karena gangguan aliran arterial atau menurunnya
drainasi venula
venula.. Iskemia dapat menyebabkan hipoksia
hipoksia..
Contoh: Pneumonia, mengakibatkan berkurangnya
Contoh:
kemampuan mengangkut oksigen dan keracunan CO.

Penyebab Jejas Sel

Agen Kimiawi (Chemical Agents):
Agents):
Polusi udara
Insektisida
CO
Asbestos
Ethanol
Obat--obatan (Bab VIII)
Obat

Penyebab Jejas Sel

Infeksi (Infectious agents):
agents):
Ricketsia
Bakteri
Jamur
Protozoa (Bab
(Bab IX)

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Penyebab Jejas Sel

Reaksi Imunologis
(Immunologic infections):
Reaksi alergi (Bab V)

Penyebab Jejas Sel

Kelainan genetis (Genetic defect):
defect): Down
syndrome,, Sickle cell anemia,
syndrome
anemia, dsb
dsb..
Ketidakseimbangan nutrisi
nutrisi:: Protein
Protein--calorie
insufficiency, vitamin deficiency, obesity, type II
DM.
Penuaan

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Mekanisme Jejas Sel

Respon seluler bergantung tipe
tipe,, durasi
durasi,, dan
keparahan jejas
jejas..
Akibat jejas bergantung tipe
tipe,, status,
kemampuan adaptasi
adaptasi,, perbaikan genetis sel
yang mengalami jejas
jejas..
Disebabkan oleh abnormalitas fungsional dan
biokimiawi..
biokimiawi

Deplesi ATP

(ATP Depletion)

The initial
functional and
morphologic
consequences of
decreased
intracellular
adenosine
triphosphate
(ATP) during cell
injury. ER,
Endoplasmic
reticulum.

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Kerusakan
Mitokondria
(Damage to
Mitochondria)
Consequences of
mitochondrial
dysfunction, culminating
in cell death by necrosis
or apoptosis. ATP,
Adenosine tri
tri--phosphate
phosphate..

Influks Kalsium
(Influx of Ca)
Sources and
consequences of
increased cytosolic
calcium in cell
injury. ATP,
Adenosine
triphosphate;
ATPase, adenosine
triphosphatase.

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Stres Oksidatif (Akumulasi ROS, reactive oxygen species)

species)

Mekanisme terjadinya kerusakan pada membran cell

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Accumulation of damaged DNA and

misfolded protein

Morfologi Jejas
Reversibel:
Cellular swelling: Terjadi karena kegagalan pompa
energy- dependent ion pada plasma membran, yang
mengakibatkan ketidakmampuan dalam menjaga
kesetimbangan ion dan cairan.
Fatty change: Terjadi pada hipoksia, jejas toksis, dan
jejas metabolis misalnya pada sel hepar dan myokardial.

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The relationship between cellular function, cell

death, and the morphologic changes of cell
injury. Note that cells may rapidly become
nonfunctional after the onset of injury, although
they are still viable, with potentially reversible
damage; a longer duration of injury may
eventually lead to irreversible injury and cell
death. Note also that cell death typically
precedes ultrastructural
ultrastructural,, light microscopic, and
grossly visible morphologic changes.

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Perubahan Struktural Reversibel

Alterasi plasma membran: Misal distorsi
mikrovilus, hilangnya perlekatan interseluler.
Perubahan mitokondrial.
RE dilasi dengan hilangnya perlekatan ribosom
dan disosiasi polisom.
Alterasi nuklear.

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Morphologic changes in reversible and irreversible cell injury

(necrosis). A, Normal kidney tubules with viable epithelial cells. B,
Early (reversible) ischemic injury showing surface blebs, increased
eosinophilia of cytoplasm, and swelling of occasional cells. C,
Necrotic (irreversible) injury of epithelial cells, with loss of nuclei and
fragmentation of cells and leakage of contents. The ultrastructural
features of these stages of cell injury are shown in Fig. 1-9.
(Courtesy of Drs. Neal Pinckard and M.A. Venkatachalam, University
of Texas Health Sciences Center, San Antonio.)

Nekrosis
Serangkaian perubahan yang menyertai
kematian sel.
Biasanya disebabkan karena degradasi kerja
enzim pada sel yang mengalami kematian.
Sel nekrosis tidak dapat mempertahankan
integritas membran sel dan menyebabkan
keluarnya cairan/substansi pada sel.

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Bagaimana Morfologi
Sel Nekrosis
Nekrosis??

Eusonofil meningkat
meningkat:: Pewarnaan merah jambu
eosin meningkat karena
karena::

Peningkatan ikatan eosin dengan sitoplasma yang mengalami

denaturasi..
denaturasi
Hilangnya basofil

Glassy homogenous karena hilangnya partikel

glikogen..
glikogen
Nuclear shrinkage (Cari istilah
istilah--istilah berikut
berikut,,
ya!):
ya
!):

Karyolysis
Pyknosis
Karyorerhexis

Pola--pola Nekrosis
Pola
Koagulatif

Komponen sel mengalami kematian tetapi arsitektur jaringan bertahan dalam beberapa hari
hari..

Liquefaktif: Disebabkan oleh fokal bakteria

Liquefaktif:
bakteria,, infeksi jamur
jamur,,
karena mikroba merangsang sel
sel--sel inflamasi dan enzim pada
leukosit mencerna (liquefy) jaringan
jaringan.. Transformasi jaringan
menjadi massa cair kental (misal nanah pada inflamasi akut
akut))
Kaseous (Caseous
Caseous// Cheese like)
like)
Jaringan nekrosis dengan sel terfragmentasi atau sel lisis disertai granula berbentuk tidak beraturan
beraturan.. Khas pada granuloma
granuloma..

Fat necrosis:
necrosis: Tandanya fat saponification
saponification,, area putih seperti
kapur..
kapur
Fibrinoid necrosis
Tampak pada reaksi imun yang melibatkan pembuluh darah
darah.. Complek antigen antibodi tertimbun pada dinding pembuluh darah
arteri.Bersama dengan fibrin membentuk gambaran fibrinoid
fibrinoid..

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Coagulative necrosis. A, A wedge-shaped kidney infarct

(yellow) with preservation of the outlines. B, Microscopic view
of the edge of the infarct, with normal kidney (N) and necrotic
cells in the infarct (I). The necrotic cells show preserved
outlines with loss of nuclei, and an inflammatory infiltrate is
present (difficult to discern at this magnification).

Liquefactive necrosis. An infarct in the brain, showing dissolution of the tissue.

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Caseous necrosis
necrosis.. A tuberculous lung with a large area of caseous necrosis
containing yellowyellow-white and cheesy debris

Fat necrosis in acute pancreatitis. The areas of white chalky deposits represent foci of fat necrosis
with calcium soap formation (saponification) at sites of lipid breakdown in the mesentery.

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Fibrinoid necrosis in an artery in a patient with polyarteritis nodosa. The wall of the
artery shows a circumferential bright pink area of necrosis with protein deposition and
inflammation (dark nuclei of neutrophils).

Apoptosis
Kejadian bunuh diri sel.
Secara definitif adalah proses teregulasi sel mematikan
aktivitas enzim yang mampu menyebabkan degradasi sel
tertentu.
Karakteristik: degradasi enzimatik protein dan DNA,
diinisiasi oleh kaspase (caspase), pengenalan dan
penghilangan sel yang mati oleh fagosit.

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Penyebab Apoptosis: Fisiologis

Destruksi saat embriogenesis
Involusi hormone-dependent tissue: saat menstruasi
atau saat berhenti breast feeding.
Hilangnya sel pada populasi sel yang mengalami
proliferasi.
Kematian sel setelah selesai menjalankan fungsinya,
misal setelah inflamasi dan respon imunologis
tertentu.
Eliminasi sel pasca maturasi.
Kematian sel karena induksi T-limfosit.

Penyebab Apoptosis: Patologis

Kerusakan DNA: Radiasi
Radiasi,, Obat antikanker sitotoksis
sitotoksis,, perubahan
temperatur ekstrem
ekstrem,, atau hipoksia (karena radikal bebas
bebas).
).
Akumulasi misfolded protein
protein:: ER stress.
Jejas sel pada beberapa infeksi yang diinduksi oleh virus
(Adenovirus, HIV) atau host
host--immune response (viral hepatitis).
Atrofi patologis pada organ parenkhimal setelah penyumbatan
duktus misal pada pankreas
pankreas,, glandula parotid, dan ginjal
ginjal::

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Apoptosis of a liver cell in viral hepatitis. The cell is reduced in size and
contains brightly eosinophilic cytoplasm and a condensed nucleus.

Apoptosis
Dua mekanisme utama
utama::
Mitokondrial//intrinsik
Mitokondrial
intrinsik::

Hilangnya signal survival DNA, yang kemudian menginisiasi

kaspase..
kaspase

Death receptor (ekstrinsik

ekstrinsik):
):

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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 is dependent on a
balance between pro- and anti-apoptotic signals and
intracellular proteins. The figure shows the pathways
that induce apoptotic cell death, and the anti-apoptotic
proteins that inhibit mitochondrial leakiness and
cytochrome c-dependent caspase activation and thus
function as regulators of mitochondrial apoptosis.

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The principal cellular and biochemical sites of damage in cell injury. Note that loss of
adenosine triphosphate (ATP) results first in reversible injury (not shown) and culminates in
necrosis. Mitochondrial damage may lead to reversible injury and death by necrosis or
apoptosis.

Gambaran selular apoptosis dan necrosis

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Akumulasi intraselular

Penyebab:
1. Gangguan metabolisme
2. Kelainan genetik (1-antitripsin)
3. Kelainan enzim (Glycogenoses)
4. Cell tidak memiliki enzim yang secara khusus
mendegradasi exogenous substansia.
Akumulasi intrasellular:
1. Timbunan lemak
2. Timbunan protein
3. Timbunan glikogen
4. Timbunan pigmen
5. Kalsifikasi patologis:
a. Dystrophic calcification
b. Metastatic calcification

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Cellular Aging
Cellular aging is the result of progressive decline in the
proliferative capacity and life span of cells and the effects
of continuous exposure to exogenous factors that cause
accumulation of cellular and molecular damage

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