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APOPTOSIS &

NEKROSIS
Monita Sugianto
Dosen Pengampu:
Edhyana K. Sahiratmadja, dr., PhD
The relationship among cellular function, cell death, and
the
morphologic changes of cell injury
Henriquez M, Armisn R, Stutzin A, Quest AFG. Cell death by necrosis, a regulated way to go. Curr Mol Med. 2008;8(3):187206.
APOPTOSIS VS NECROSIS

Kumar et al. Robbins & Cotran Basic Pathology, 8th ed. Elsevier. 2007. 1-5 p.
MORPHOLOGICAL CHANGES

Kumar et al. Robbins & Cotran Basic Pathology, 8th ed. Elsevier. 2007. 1-5 p.
APOPTOSIS
A pathway of cell death by a tightly regulated
suicide program PROGRAMMED CELL DEATH
homeostasis

Apoptosis was rst used in a nowclassic paper by


Kerr, Wyllie, and Currie in 1972

From the Greek word meaning falling off as


leaves from a tree
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell, 5th edition by B. Alberts, A. Johnson, J.
Lewis, M. Raff, K. Roberts, and P. Walter. Vol. 36, Biochemistry and Molecular Biology Education. 2008.
Apoptosis in Physiologic Situations
The programmed destruction of cells during
embryogenesis.
Involution of hormone-dependent tissues upon hormone
deprivation
Cell loss in proliferating cell populations
Elimination of cells that have served their useful purpose
Elimination of potentially harmful self-reactive
lymphocytes,
Cell death induced by cytotoxic T lymphocytes

Kumar et al. Robbins & Cotran Basic Pathology, 8th ed. Elsevier. 2007. 1-5 p.
Apoptosis in Pathologic Conditions
DNA damage
Accumulation of misfolded proteins.
Cell injury in certain infections
Pathologic atrophy in parenchymal organs
after duct obstruction

Kumar et al. Robbins & Cotran Basic Pathology, 8th ed. Elsevier. 2007. 1-5 p.
Regulation of Apoptotic

PRO- ANTI-
APOPTOTIC APOPTOTIC
SENSOR
BAX BCL-2
BAK BCL-XL
Bad
BCL-XS
Bim
Bid
Puma

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell, 5th edition by B. Alberts, A. Johnson, J.
Lewis, M. Raff, K. Roberts, and P. Walter. Vol. 36, Biochemistry and Molecular Biology Education. 2008.
Apoptosis Pathway
Most important player

Cystein- Aspartate proteases


dependent - directed

Procaspases CASPASES
Ekstrinsik
pathway Initiator executioner
Intrinsik caspase caspase
Pathway

Caspases Caspases
2,8,9,10 3,6,7
Kumar et al. Robbins & Cotran Basic Pathology, 8th ed. Elsevier. 2007. 1-5 p.
Hotchkiss RS, Strasser A, McDunn et al JE. Cell death. N Engl J Med [Internet]. 2009;361(16):157083. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/19828534
EKSTRINSIC PATHWAY

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell, 5th edition by B. Alberts, A. Johnson, J.
Lewis, M. Raff, K. Roberts, and P. Walter. Vol. 36, Biochemistry and Molecular Biology Education. 2008.
INTRINSIC PATHWAY

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell, 5th edition by B. Alberts, A. Johnson, J.
Lewis, M. Raff, K. Roberts, and P. Walter. Vol. 36, Biochemistry and Molecular Biology Education. 2008.
Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny M V, et al. Molecular definitions of cell death subroutines:
recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ [Internet]. 2012;19(1):10720. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/21760595%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3252826
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell, 5th edition by B. Alberts, A. Johnson, J.
Lewis, M. Raff, K. Roberts, and P. Walter. Vol. 36, Biochemistry and Molecular Biology Education. 2008.
Inhibitors Of Apoptosis (IAPs)
First identified in
certain insect
viruses
To prevent a host
cell from killing
itself by apoptosis
The of mammalian
anti-IAP proteins in
apoptosis is more
controversial
NECROSIS
Necrosis from the Greek necros, for corpse
The type of cell death loss of membrane
integrity and leakage of cellular contents
culminating in dissolution of cells resulting
from protein denaturation and the
degradative action of enzymes on lethally
injured cells.
Irreversible

Kumar et al. Robbins & Cotran Basic Pathology, 8th ed. Elsevier. 2007. 1-5 p.
ETIOLOGI NEKROSIS
1. Iskhemi
- akibat : anoksia atau hipoksia seluler
- Obs. Aliran darah, anemia (pembawa O2 kurang), intoxikasi CO, peny.
Paru (O2)
2. Agens biologic
- toxin (bakteri, virus, parasite)
3. Agens kimia
- tubuh : Na & glukosa () keseimbangan osmosis terganggu
nekrosis
- luar : gas kloroform merusak parenkim hati
4. Agens fisik
- trauma, suhu ektrim, listrik, cahaya, radiasi kerusakan inti nekrosis
5. Kerentanan (hypersensitivity)
- hipersensitii pada obat sulfat nekrosis tubulus ginjal (variasi individu)

Kumar et al. Robbins & Cotran Basic Pathology, 8th ed. Elsevier. 2007. 1-5 p.
KLASIFIKASI
3. Nekrosis Kaseosa
Infeksi TB

1. Nekrosis Koagulative
Infark GInjal

4. Nekrosis Lemak
Komplikasi Pankreatitis
2. Liquefactive Necrosis
Infark otak & abses

5. Nekrosis Fibrinoid
Penyakit Autoimun & malignancy
HISTOPHATOLOGY

Kumar et al. Robbins & Cotran Basic Pathology, 8th ed. Elsevier. 2007. 1-5 p.
MORPHOLOGICAL CHANGES
Cytoplasmic changes
Nuclear changes
Karyolisis
Pyknosis
karyorrhexis
Fates of necrotic cell
Sel nekrotik dapat bertahan beberapa lama atau dapat
dicerna oleh enzim dan hilang. Sel mati dapat digantikan oleh
myelin, yang keduanya difagositosis atau terdegradasi lebih
lanjut menjadi asam lemak. Asam lemak ini mengikat garam
kalsium, yang bisa menyebabkan sel mati akhirnya menjadi
kalsifikasi.

Kumar et al. Robbins & Cotran Basic Pathology, 8th ed. Elsevier. 2007. 1-5 p.
The principal targets and
biochemical
mechanisms of cell injury
(1) mitochondria and their ability to generate
ATP and ROS under pathologic conditions;
(2) disturbance in calcium homeostasis;
(3) damage to cellular (plasma and lysosomal)
membranes;
(4) damage to DNA and misfolding of proteins.

Kumar et al. Robbins & Cotran Basic Pathology, 8th ed. Elsevier. 2007. 1-5 p.
Mechanisms of Cell Injury
ATP depletion: failure of energy-dependent functions
reversible injury necrosis
Mitochondrial damage: ATP depletion failure of energy
dependent cellular functions ultimately, necrosis;
undersome conditions, leakage of mitochondrial proteins
that cause apoptosis
Influx of calcium: activation of enzymes that damage
cellular components and may also trigger apoptosis
Accumulation of reactive oxygen species: covalent
modification of cellular proteins, lipids, nucleic acids
Increased permeability of cellular membranes: may affect
plasma membrane, lysosomal membranes, mitochondrial
membranes; typically culminates in necrosis
Accumulation of damaged DNA and misfolded proteins:
triggers apoptosis
Kumar et al. Robbins & Cotran Basic Pathology, 8th ed. Elsevier. 2007. 1-5 p.
DEPLETION ATP
Mitochondrial
Damage and
Dysfunction
Influx of
Calcium
Accumulation of Oxygen-Derived Free Radicals
(Oxidative Stress)
Defects in Membrane
Permeability
TERIMA KASIH
Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny M V, et al. Molecular definitions of cell death subroutines:
recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ [Internet]. 2012;19(1):10720. Available
from: http://www.ncbi.nlm.nih.gov/pubmed/21760595%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3252826